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Name
Fang Li
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Capital Medical University
Country
China

Publications Authored By Fang Li

Remote ischemic postconditioning (RIPostC) has been proved to protect the brain from stroke, but the precise mechanism remains not fully understood. In the present study, we aimed to investigate whether RIPostC attenuates cerebral ischemia-reperfusion injury by abating endoplasmic reticulum (ER) stress response. CHOP, a multifunctional transcription factor in ER stress, regulates the expression of genes related to apoptosis, such as Bim and Bcl-2.Read More

Male SD rats were subjected to right middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion, and RIPostC was induced by three cycles of 10 min ischemia and 10 min reperfusion on bilateral femoral arteries immediately after ischemia. CHOP siRNA (CHOPi) and control siRNA (Coni) were injected into the right lateral ventricle 30 min before the beginning of ischemia. RIPostC, CHOPi, or RIPostC + CHOPi application reduced infarct volume, improved the neurological function, and decreased cell apoptosis. RIPostC increased the protein level of glucose-regulated protein 78 (GRP78) and decreased the protein level of phosphorylated-EIF2α, caspase-12, and CHOP. Furthermore, the expression of CHOP, Bim and cleaved-caspase-3 was decreased, while Bcl-2 expression was increased in response to application of RIPostC, CHOPi, or RIPostC + CHOPi. In sum, RIPostC protects against ischemia-reperfusion brain injury in rats by attenuating ER stress response-induced apoptosis.

TNF-like ligand 1A (TL1A), a newly identified member of the TNF superfamily, has been proved as an important mediator of inflammation and critically involved in the pathogenesis of rheumatoid arthritis and several other autoimmune diseases. The aim of our study was to determine the possible role of TL1A in the pathogenesis of psoriasis. In this study, serum levels of TL1A in patients with psoriasis vulgaris (PV) and atopic dermatitis (AD) were detected by enzyme-linked immunosorbent assay (ELISA).Read More

Then, peripheral blood mononuclear cells (PBMCs) from patients with PV were isolated, the mRNA expression of TL1A was measured by real-time quantitative PCR. The effects of TL1A on the production of T cell cytokines, such as IL-17, IFN-γ, IL-4 and IL-10 in PBMCs were determined. We demonstrated that serum TL1A levels were significantly elevated in patients with PV but not in patients with AD. Besides, the high serum TL1A levels in patients with PV decreased after treatment. PBMCs derived from psoriatic patients showed significantly increased TL1A mRNA levels. Soluble TL1A synergized with IL-23 to stimulate PBMCs from patients with PV to produce IL-17. Taken together, these findings strongly suggest that TL1A may play a role in the pathogenesis of PV.

Families play an important role in the lives of individuals with mental illness. Coping with the strain of shifting roles and multiple challenges of caregiving can have a huge impact. Limited information exists regarding race-related differences in families' caregiving experiences, their abilities to cope with the mental illness of a loved one, or their interactions with mental health service systems.Read More

This study examined race-related differences in the experiences of adults seeking to participate in the National Alliance on Mental Illness Family-to-Family Education Program due to mental illness of a loved one. Participants were 293 White and 107 African American family members who completed measures of problem- and emotion-focused coping, knowledge about mental illness, subjective illness burden, psychological distress, and family functioning. Multiple regression analyses were used to determine race-related differences. African American caregivers reported higher levels of negative caregiving experiences, less knowledge of mental illness, and higher levels of both problem-solving coping and emotion-focused coping, than White caregivers. Mental health programs serving African American families should consider targeting specific strategies to address caregiving challenges, support their use of existing coping mechanisms and support networks, and increase their knowledge of mental illness.

Gene fusion is among the primary processes that generate new genes and has been well characterized as potent pathway of oncogenesis. Here, by high-throughput RNA sequencing in nine paired human endometrial carcinoma (EC) and matched non-cancerous tissues, we obtained that chimeric translin-associated factor X-disrupted-in-schizophrenia 1 (TSNAX-DISC1) occurred significantly upregulated in multiple EC samples. Experimental investigation showed that TSNAX-DISC1 appears to be formed by splicing without chromosomal rearrangement.Read More

The chimera expression inversely correlated with the binding of CCCTC-binding factor (CTCF) to the insulators. Subsequent investigations indicate that long intergenic non-coding RNA lincRNA-NR_034037, separating TSNAX from DISC1, regulates TSNAX -DISC1 production and TSNAX/DISC1 expression levels by extricating CTCF from insulators. Dysregulation of TSNAX influences steroidogenic factor-1-stimulated transcription on the StAR promoter, altering progesterone actions, implying the association with cancer. Together, these results advance our understanding of the mechanism in which lincRNA-NR_034037 regulates TSNAX-DISC1 formation programs that tightly regulate EC development.

The tumor-promoting arm of transforming growth factor beta (TGF-β) receptor signaling contributes to advanced cancer progression and is considered a master regulator of breast cancer metastasis. In mammals, there are six distinct members in the tumor-necrosis factor receptor (TNFR)-associated factor (TRAF) family (TRAF1-TRAF6), with the function of TRAF4 not being extensively studied in the past decade. Although numerous studies have suggested that there is elevated TRAF4 expression in human cancer, it is still unknown in which oncogenic pathway TRAF4 is mainly implicated.Read More

This review highlights TGF-β-induced SMAD-dependent signaling and non-SMAD signaling as the major pathways regulated by TRAF4 involved in breast cancer metastasis.

Vascular dementia (VaD) is the second most prevalent type of dementia among the aged, for whom limited pharmacologic options are available so far. SaiLuoTong capsule is a modern traditional Chinese medicine formula, which has been demonstrated to improve cognition of VaD by the reports of animal experiments and preliminary clinical trial. However, evaluation of this therapy in randomized multicenter trials is needed.Read More

In this article, we present the rationale and design of the SaiLuoTong in Vascular Dementia Study.
This phase 2 clinical trial of SaiLuoTong among patients with mild-to-moderate VaD is a 26-week, multicenter, randomized, double-blind, placebo-controlled study with a subsequent 26-week, open-label extension. After a 4-week placebo run-in period, participants are centrally randomized (1:1:1) to 3 groups: group A receives SaiLuoTong 360 mg per day for 52 weeks; group B receives SaiLuoTong 240 mg per day for 52 weeks; group C (the control group) are further randomly assigned to 2 groups in a 1:1 ratio and receives placebo during the double-blind phase, then SaiLuoTong 360 mg per day or SaiLuoTong 240 mg per day during the extension phase. The primary outcome measures include the VaD assessment scale cognitive subscale and the Alzheimer Disease Cooperative Study-clinical global impression of change. Safety measures include body weight, vital signs, electrocardiography, laboratory tests, and records of adverse events. Assuming an attrition rate of 20%, at least 372 patients are required to obtain a statistical power of 80%.
The first patient was enrolled into the study in April 2012 and the completion of the study is expected in September 2014.
The rigorous methodology of the study will hopefully move forward the scientific evaluation of traditional Chinese medicine in treatment of VaD. The results of the present study will provide high-quality evidence on the effect of SaiLuoTong in patients with VaD and has the potential to establish a novel therapeutic approach for this disorder.

2014Dec

Tumor cell surface aminopeptidase N (APN or CD13) has two puzzling functions unrelated to its enzymatic activity: mediating tumor cell motility and serving as a receptor for tumor-homing peptides (peptides that bring anti-cancer drugs to tumor cells). To investigate APN-based tumor-homing therapy, we determined the crystal structure of APN complexed with a tumor-homing peptide containing a representative Asn-Gly-Arg (NGR) motif. The tumor-homing peptide binds to the APN enzymatic active site, but it resists APN degradation due to a distorted scissile peptide bond.Read More

To explore APN-based tumor cell motility, we examined the interactions between APN and extracellular matrix (ECM) proteins. APN binds to, but does not degrade, NGR motifs in ECM proteins that share similar conformations with the NGR motif in the APN-bound tumor-homing peptide. Therefore, APN-based tumor cell motility and tumor-homing therapy rely on a unified mechanism in which both functions are driven by the specific and stable interactions between APN and the NGR motifs in ECM proteins and tumor-homing peptides. This study further implicates APN as an integrin-like molecule that functions broadly in cell motility and adhesion by interacting with its signature NGR motifs in the extracellular environment.

The aim of the present study was to explore the use of high frequency color Doppler ultrasound to measure synovial thickness and blood flow to assess the therapeutic value of the recombinant human tumor necrosis factor (TNF) II receptor antibody fusion protein in rheumatoid arthritis (RA) treatment. A total of 36 clinically-diagnosed patients with RA were treated with methotrexate tablets or the recombinant TNF-receptor antibody fusion protein for 24 weeks. Joint synovial thickness and synovial blood flow integrity were monitored by high frequency color Doppler in the second metacarpophalangeal joint in one hand.Read More

The correlation of the erythrocyte sedimentation rate, C-reactive protein (CRP) and 28-joint disease activity score (DAS28) with the ultrasound parameters were analyzed. Metacarpophalangeal second joint 2 (MCP2) synovial thickness, wrist joint synovial thickness and MCP2 synovial blood flow, prior and subsequent to the treatment, have a high correlation with DAS28 (P<0.05), and the MCP2 synovial blood flow integral has a strong correlation with CRP. Evaluating the wrist joint synovial thickness and synovial integrity of the second metacarpophalangeal joint using high frequency ultrasound detection can effectively evaluate the disease status in patients with RA. This procedure is potentially valuable as a means of evaluating the curative effects of RA treatments.

This study aims at using 18F-FDG microPET to monitor the brown adipose tissue (BAT) glucose metabolism in obese and diabetic mouse models under different interventions, and study the therapeutic potential of BAT activation for weight loss and lowering of blood glucose in these models.
Obese mice were established by a high-fat diet for eight weeks, and diabetes mellitus(DM) models were induced with Streptozocin in obese mice. 18F-FDG microPET was used to monitor BAT function during obese and DM modeling, and also after BRL37344 (a β3-adrenergic receptor agonist) or levothyroxine treatment.Read More

The BAT function was correlated with the body weight and blood glucose levels.
Compared with the controls, the obese mice and DM mice showed successively lower 18F-FDG uptake in the interscapular BAT (P = 0.036 and <0.001, respectively). After two-week BRL37344 treatment, the BAT uptake was significantly elevated in both obese mice (P = 0.010) and DM mice (P = 0.004), accompanied with significantly decreased blood glucose levels (P = 0.023 and 0.036, respectively). The BAT uptake was negatively correlated with the blood glucose levels in both obese mice (r = -0.71, P = 0.003) and DM mice (r = -0.74, P = 0.010). BRL37344 treatment also caused significant weight loss in the obese mice (P = 0.001). Levothyroxine treatment increased the BAT uptake in the control mice (P = 0.025) and obese mice (P = 0.013), but not in the DM mice (P = 0.45).
The inhibited BAT function in obese and DM mice can be re-activated by β3-adrenergic receptor agonist or thyroid hormone, and effective BAT activation may lead to weight loss and blood glucose lowering. Activating BAT can provide a new treatment strategy for obesity and DM.

2014Dec

To observe the changes in forkhead/winged helix transcription factor p3(Foxp3), regulatory T cells (Treg), retinoid-related orphan receptor gamma (RORγt) in rat model of chronic obstructive pulmonary disease (COPD).
Twenty Sprague-Dawley (SD) rats were randomly divided into normal control group and COPD model group, with 10 rats in each group. The COPD model was reproduced by smoke inhalation and tracheal instillation of lipopolysaccharide (LPS), and no such treatment was conducted in normal control group.Read More

Twenty-eight days after the model reproduction, the pulmonary function was determined, the pathological changes of lung tissue were observed with haematoxylin-eosin (HE) staining, interleukins (IL-6, IL-10) in serum were detected by enzyme-linked immunosorbent assay (ELISA), CD4(+)CD25(+)Foxp3(+) Treg of peripheral blood was determined by flow cytometry, and the expressions of Foxp3, RORγt, IL-17 protein in lung tissue were assayed by Western Blot.
Under light microscope, significal interstitial infiltration of inflammatory cells was found in alveoli and interstitial tissue of the lung, and destruction of alveolar tissue, alveolar wall thinning, and even rupture to fuse into bullae, and bleeding into alveoli in different degress could be observed. Compared with the normal control group, forced vital capacity (FVC), forced expiratory volume in 0.3 second (FEV0.3), FEV0.3/FVC, peak expiratory flow (PEF) in model group were significantly decreased [FVC (mL): 8.04±2.03 vs. 9.97±2.14, FEV0.3 (mL): 6.16±2.23 vs. 8.84±2.12, FEV0.3/FVC: 0.70±0.09 vs. 0.85±0.11, PEF (mL/s): 33.56±4.76 vs. 40.14±5.64, P<0.05 or P<0.01]. Serum IL-6 was obviously increased (ng/L: 93.17±20.96 vs. 76.28±13.24, P<0.05), IL-10 was significantly decreased (ng/L: 78.62±15.17 vs. 104.34±19.46, P<0.01), and CD4(+)CD25(+)FoxP3(+)Treg was significantly diminished [(2.75±0.83)% vs. (4.16±1.14)%, P<0.01] in model group compared with those in the normal control group. The expression of Foxp3 protein in lung tissue in model group was significantly down-regulated compared with that in the normal control group (gray scale: 0.38±0.15 vs. 0.63±0.11, P<0.01), and RORγt and IL-17 protein expressions were significantly up-regulated [RORγt (gray scale): 0.96±0.23 vs. 0.47±0.11, IL-17 (gray scale): 1.02±0.24 vs. 0.34±0.08, both P<0.01]. Correlation analysis showed that FEV0.3 was positively correlated with Foxp3 (r=0.585, P<0.05), and FEV0.3/FVC was negatively correlated with IL-6 and RORγt(r=-0.655, r=-0.607, both P<0.05). PEF was positively correlated with Treg (r=0.573, P<0.05), and negatively correlated with IL-17 (r=-0.198, P<0.05). IL-6 was negatively correlated with Foxp3(r=-0.603, P<0.05),and positively correlated with RORγt (r=0.588, P<0.05). IL-10 was positively correlated with Treg (r=0.573, P<0.05). Treg was positively correlated with Foxp3 (r=0.607, P<0.05), and negatively correlated with IL-17 (r=-0.569, P<0.05). Foxp3 was negatively correlated with RORγt(r=-0.591, P<0.05). RORγt was positively correlated with IL-17 (r=0.578, P<0.05).
There is a relationship among decreased pulmonary function, inflammation and imbalance of Foxp3/Treg and RORγt/Th17 in COPD.

The current paper aims to study the effect of adenovirus-mediated IL-24 (Ad-IL-24) on human lung adenocarcinoma in vitro and in vivo and determine its possible mechanism of action. The growth-suppressing and apoptosis-inducing effects of Ad-IL-24, radiotherapy, and Ad-IL-24+ radiotherapy (hereinafter referred to as the joint group) on SPC-A1 lung carcinoma cells were assessed by using 3-(4,5-dimethyliazolyl-2)-2,5-diphnyltetrazolium bromide and flow cytometry. A human lung model was established with SPC-A1 cells in nude mice.Read More

Groups of mice were subjected to multi-point injections to their tumors. Gross tumor volumes were measured dynamically. The ratios of tumor suppression and radiosensitization effect were evaluated according to the method of probability sum Q values. The expressions of Bax, Bcl-2, Survivin, and Caspase-3 in tumor samples were detected by immunohistochemistry. The ratios of inhibition and apoptosis in the joint group were higher than those in the individual Ad-IL-24 and radiotherapy groups. In vitro, the joint group suppressed tumor growth conspicuously, showing a weight inhibition rate of about 64 %. The expressions of FasL, Bax and Caspase-3 were upregulated in the joint group, while the expressions of Cox,Bcl-2,VEGF,CD34 and Survivin were downregulated. The current study proves that Ad-IL-24 suppresses growth of SPC-A1 cells both in vitro and in vivo. Its functions appear to be related to cell apoptosis and antiangiogenesis.

Background:C - reactive protein (CRP) has been associated with cancer risk in some prospective studies. However, the associations have not been entirely consistent and have not been evaluated in Chinese females. We conducted a large population-based cohort study to investigate whether elevated levels of CRP at baseline are associated with an increased risk of cancer among Chinese females.Read More

Methods:19,437 women from the Chinese Kailuan Female Cohort were enrolled in the study in July 2006. Levels of high-sensitivity CRP (hsCRP) were tested at baseline for all subjects. Multivariable Cox proportional hazards regression models were used to evaluate the association between levels of hsCRP and risk of all cancers, including breast cancer, lung cancer, colorectal cancer, and other cancers. Results:By Dec 31, 2011, a total of 322 incident cancer cases accrued. Compared to women with lower hsCRP levels (<1mg/L), women with higher hsCRP (>3mg/L) had a significantly increased risk of all incident cancers (HR=1.62, 95% CI =1.23-2.14; Ptrend = 0.001) and breast cancer (HR = 1.74, 95% CI = 1.01-2.97; Ptrend = 0.047). The significant association between hsCRP levels and breast cancer risk was apparent among younger women (<50 years) (HR=2.76, 95% CI = 1.18-6.48). Conclusion:Elevated levels of hsCRP at baseline may be associated with an increased risk of cancer, especially breast cancer, and particularly in younger Chinese women. Impact:Our findings provide additional evidence for a role of inflammation in carcinogenesis and suggest that CRP may be a potentially useful biomarker of cancer risk in this population.

Controlled release plays an essential role in formulating topical and transdermal drug delivery systems. In this study, we correlated the skin permeation of Sesamin, a lipophilic drug, with the rheological properties of two different organogel carriers, i.e.Read More

, low molecular weight gelling agent N-lauroyl-L-glutamic acid di-n-butylamide (GP-1) and Carbopol polymeric gels. Although these two gels have distinct network structures, they share the same trend: the more rigid the gel network and the higher the gelator concentration, the lower the steady flux of Sesamin through skin. This negative correlation lies in the fact that organogel network hinders the diffusion of drug to the gel-skin interface, as a result the depletion zone near the interface is non-negligible and contributes to the resistance of the whole diffusion system, thus the permeation flux is reduced. More interestingly, the dependence of the steady flux against gel complex modulus at the linear viscoelastic region followed a 'universal' power law regardless of the gel types, i.e., 1/J = 1/J0 + a.(G*)ε/C0 with a = 11.25, ε = 0.21 ± 0.03 for GP-1 gels, and a = 0.16, ε = 1.05 ± 0.06 for Carbopol gels, J0 is the steady flux without gel (G* = 0), C0 is the initial concentration of drug in gels. The empirical formulae are crucial in developing transdermal organogel systems with controlled release of drug content through readily obtainable data of their rheological properties. The explanation for the power law dependence of the steady flux on gel complex modulus is discussed.

BackgroundAcupuncture has analgesic effect to most pain conditions. Many neuroimaging studies were conducted to explore acupoint specificity in pain and other condition, but till now there is still discrepancy. Based on our previous finding, this study investigated the brain metabolism changes of acupuncture analgesia induced by sub-specific acupoint and non-acupoint stimulation.Read More

Methods30 migraineurs were included and randomly assigned to 3 groups: Acupuncture Group (AG), Sham Acupuncture Group (SAG) and Migraine Group (MG). In AG, a combination sub-specific points of Shaoyang meridians, Luxi (TE19), San Yangluo (TE8), and Xi Yangguan(GB33) has been stimulated with electroacupuncture, while non-acupoints for SAG were used and MG received no treatment. Positron emission tomography with computed tomography (PET-CT) was used to identify differences in brain glucose metabolism between groups.ResultsIn the AG, brain glucose metabolism increase compared with the MG was observed in the middle frontal gyrus, postcentral gyrus, the precuneus, parahippocampus, cerebellum and middle cingulate cortex (MCC), and decrease were observed in the left hemisphere of Middle Temporal Cortex (MTC).In the SAG, compared with MG, glucose metabolism increased in the poster cingulate cortex (PCC), insula, inferior temporal gyrus, MTC, superior temporal gyrus, postcentral gyrus, fusiform, inferior parietal lobe, superior parietal lobe, supramarginal gyrus, middle occipital lobe, angular and precuneus; while, decreased in cerebellum, parahippocampus.ConclusionsAcupuncture stimulation at both sub-specific acupoint and non-acupoint yields ameliorating effect to migraine pain, but with evidently differed central mechanism as measured by PET-CT. The pattern of brain glucose metabolism change in acupoint is pertinent and targeted, while in non-acupoint that was disordered and randomized. These finding may provide new perspectives into the validation of acupoint specificity, optimizing acupuncture analgesia and revealing central mechanism of acupuncture analgesia by neuroimaging measurement.Trial registrationThis trial was registered in the Chinese Clinical Trial Registry, with registration no. ChiCTR-TRC-11001813.

Cisplatin (DDP), a cytotoxic antitumor drug, functions in a dose-dependent manner. However, the pursuit for high‑dose therapeutic effects leads to more serious side effects including kidney toxicity. Nephrotoxicity caused due to endothelial cell dysfunction and neutrophils infiltration in kidneys.Read More

Interleukin-8 (IL-8) is an ELR+ chemokine binds with CXCR1/2 receptors and its role is primarily in neutrophils recruitment and also involved in invasion, angiogenesis and metastasis of different solid tumors including liver cancer. G31P, a CXCR1/2 antagonist, binds with CXCR1/2 with high affinity, and acts as an anti-inflammatory and antitumor agent. In the present study, we examined the antitumor effects of G31P and DDP on mouse liver cancer cells, and the effects exerted by G31P on cisplatin-induced renal injury. In vitro, effects of the G31P and DDP regimen on H22 cell proliferation were investigated by MTT assay. In vivo BALB/c mice were inoculated subcutaneously with 1x106 H22 cells and treated after one week with a high single dose of DDP with and without G31P on alternative days until the experiment was terminated. On the 15th day the mice were sacrificed, dissected and kidney tissues were analyzed using H&E staining. Myeloperoxidase (MPO) activity was assessed and RT-PCR was performed to detect inflammatory cytokines. Solid tumors were weighed for tumor growth and performed pathological examination, immunohistochemistry and western blotting were performed to detect tissue-related protein expressions in tumor tissue. The tumor inhibitory rate of DDP, G31P and DDP+G31P groups was 38.40, 40.74 and 74.80%, respectively, and the general state of mice in the DDP+G31P group was significantly improved as compared to the DDP group. The results indicated that G31P with DDP significantly inhibited the proliferation while the growth of H22 cell carnimona in vitro and in vivo enhanced the efficacy of cisplatin in cancer treatment with reduced side effects on acute renal failure.

Quorum sensing (QS) is a means of cell-to-cell communication that uses diffusible signaling molecules that are sensed by the population to determine population density, thus allowing co-ordinate gene regulation in response to population density. In Pseudomonas aeruginosa, production of the QS signaling molecule, N-acyl homoserine lactone (AHL), co-ordinates expression of key factors of pathogenesis, including biofilm formation and toxin secretion. It is predicted that the inhibition of AHL sensing would provide an effective clinical treatment to reduce the expression of virulence factors and increase the effectiveness of antimicrobial agents.Read More

We previously demonstrated that sodium houttuyfonate (SH), commonly used in traditional Chinese medicine to treat infectious diseases, can effectively inhibit QS-regulated processes, including biofilm formation. Here, using a model system, we demonstrate that SH causes the dose-dependent inhibition of AHL production, through down-regulation of the AHL biosynthesis gene, lasI. Addition of SH also resulted in down-regulation of expression of the AHL sensor and transcriptional regulator, LasR, and inhibited the production of the QS-regulated virulence factors, pyocyanin and LasA. These results suggest that the antimicrobial activity of SH may be due to its ability to disrupt QS in P. aeruginosa.

(3) JC'C' and (3) JHNHα couplings are related to the intervening backbone torsion angle ${\varphi }$ by standard Karplus equations. Although these couplings are known to be affected by parameters other than ${\varphi }$, including H-bonding, valence angles and residue type, experimental results and quantum calculations indicate that the impact of these latter parameters is typically very small. The solution NMR structure of protein GB3, newly refined by using extensive sets of residual dipolar couplings, yields 50-60 % better Karplus equation agreement between ${\varphi }$ angles and experimental (3) JC'C' and (3) JHNHα values than does the high-resolution X-ray structure.Read More

In intrinsically disordered proteins, (3) JC'C' and (3) JHNHα couplings can be measured at even higher accuracy, and the impact of factors other than the intervening torsion angle on (3) J will be smaller than in folded proteins, making these couplings exceptionally valuable reporters on the ensemble of ${\varphi }$ angles sampled by each residue.

This study is to evaluate the association between p73 G4C14-A4T14 polymorphism and squamous cell carcinoma (SCC) risk in diverse populations. We searched the PubMed, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine databases for all articles on the association between p73 G4C14-A4T14 polymorphism and SCC risk through March 2014. We performed a comprehensive meta-analysis of six case-control studies that included 1,758 SCC cases and 2,970 case-free controls.Read More

All analyses were performed using STATA 11.0, using two-sided P values. Overall, this meta-analysis showed that the p73 G4C14-A4T14 polymorphism was associated with a significantly increased risk of SCC in three genetic models. However, after excluding one study deviating from Hardy-Weinberg equilibrium, the results then demonstrated that the p73 G4C14-A4T14 polymorphism was only associated with elevated risk of cervical squamous cell carcinoma (for AT/GC vs GC/GC: OR 1.51, 95 % CI 1.14-2.00, P heterogeneity = 0.996; for AT/AT+AT/GC vs GC/GC: OR 1.42, 95 % CI 1.08-1.87, P heterogeneity = 0.994) in subgroup analysis by tumor sites. No publication bias was found in the present study. This meta-analysis suggests that the p73 G4C14-A4T14 polymorphism is associated with an increased risk of cervical squamous cell carcinoma. Further large and well-designed studies are needed to confirm this association.

Pathological mutations in the glucocerebrosidase gene (GBA) have been suggested to be associated with Parkinson's disease (PD) in various ethnic populations. Most studies on Chinese PD patients have only screened the N370S and L444P mutations in the GBA gene. To investigate the GBA mutations in Chinese population, we performed complete sequencing of the GBA gene in 184 Chinese PD patients and 130 Chinese control individuals.Read More

As a result, we identified three novel and nine reported GBA mutations. The novel mutations include 5-bp deletion (c.334_338delCAGAA), L264I and L314V and the nine reported GBA mutations are R163Q, F213I, E326K, S364S, F347L, V375L, L444P, RecNciI and Q497R. The novel 5-bp deletion (CAGAA) produces a short truncated GBA protein of 142 amino acids, which loses major function domains of the 536 amino acids. Our data also reveals that the frequency of GBA mutations within this Chinese PD cohort was 8.7%, which is significantly higher than 1.54% observed in the Chinese control cohort (χ(2)=7.22, P=0.0072; odds ratio (OR)=6.095, 95% confidence interval of OR=1.546-24.030). The most common L444P mutation accounts 2.74%, which confer more genetic risk for PD in this Chinese population. In conclusion, novel and known GBA mutations were identified and were found to be associated to PD in this Chinese population.Journal of Human Genetics advance online publication, 18 December 2014; doi:10.1038/jhg.2014.110.

2014Dec
Invest. Ophthalmol. Vis. Sci.
Invest Ophthalmol Vis Sci 2014 Dec 18. Epub 2014 Dec 18.

Purpose: Fibroblast growth factor (FGF2) is a potent endothelial cell mitogen and survival factor which is postulated to participate in the pathogenesis of retinopathy of prematurity (ROP). The purpose of the current study was to determine the transcriptional and translational regulation of FGF2 expression in oxygen-induced retinopathy (OIR), the animal model of ROP. Methods: We examined FGF2 protein and mRNA expression and optokinetic visual responses in transgenic mice possessing a dual-luciferase bicistronic transgene containing 5'- internal ribosome entry site (IRES) of FGF2.Read More

Results: We found that retinal FGF2 protein isoform expression varies with age but not in response to OIR. Analysis of luciferase, protein, and mRNA data indicate that FGF2 protein expression is translationally repressed during the vaso-obliterative phase of OIR, possibly by inhibiting elongation. At the transition from vaso-obliteration to neovascularization, heightened FGF2 protein expression corresponds to maintenance of IRES activity and diminished cap-dependent translational activity. During neovascularization, FGF2 expression is primarily regulated by transcription. Mice recovering from OIR display alterations in visual optokinetic responses and increased FGF2 protein expression at 6 weeks of age. Conclusions: In total, these findings illustrate the complexity of translational and transcriptional regulation of FGF2 protein expression in OIR. The augmentation of FGF2 expression and reduced optokinetic responses during the resolution of surface vasculopathy may indicate a role for FGF2 in the maintenance of neuroretinal function in OIR/ROP.

Previous observational studies using differing methodologies have yielded inconsistent results regarding the association between glycemic control and outcomes in diabetic patients receiving maintenance hemodialysis (MHD). The aim of this study was to investigate the association between HbA1c and survival in diabetic MHD patients in Han Chinese population.
A 5-year cohort (October 2007-December 2013) of 236 diabetic MHD patients with HbA1c data was examined for associations between HbA1c and mortality.Read More

Death hazard ratios (HR) were estimated using Cox regressions.
Two hundred and thirty-six diabetes patients undergoing MHD in clinics over 5 years were included in our study. Unadjusted survival analyses indicated paradoxically lower death HRs with higher HbA1c values. However, after adjusting for potential confounders (demographics, dialysis vintage, comorbidity, anemia, and inflammation), higher HbA1c values were incrementally associated with higher death risks.
Poor glycemic control (HbA1c ≥ 8 %) appears to be associated with decreased survival in the general population of diabetic MHD patients. Our study suggests that moderate hyperglycemia increases the risk for all-cause mortality of diabetic MHD patients in Han Chinese population.

Integrin αvβ3 is overexpressed in both neovasculature and glioma cells. We aimed to evaluate (68)gallium-BNOTA-PRGD2 ((68)Ga-PRGD2) as a new reagent for noninvasive integrin αvβ3 imaging in glioma patients. With informed consent, 12 patients with suspicious brain glioma, as diagnosed by enhanced magnetic resonance imaging (MRI) scanning, were enrolled to undergo (68)Ga-PRGD2 PET/CT and (18)F-FDG PET/CT scans before surgery.Read More

The preoperative images were compared and correlated with the pathologically determined WHO grade. Next, the expression of integrin αvβ3, CD34, and Ki-67 were determined by immunohistochemical staining of the resected brain tumor tissue. Our findings demonstrated that (68)Ga-PRGD2 specifically accumulated in the brain tumors that were rich of integrin αvβ3 and other neovasculature markers, but not in the brain parenchyma other than the choroid plexus. Therefore, (68)Ga-PRGD2 PET/CT was able to evaluate the glioma demarcation more specifically than (18)F-FDG PET/CT. The maximum standardized uptake values (SUVmax) of (68)Ga-PRGD2, rather than those of (18)F-FDG, were significantly correlated with the glioma grading. The maximum tumor-to-brain ratios (TBRmax) of both tracers were significantly correlated with glioma grading, whereas (68)Ga-PRGD2 seemed to be more superior to (18)F-FDG in differentiating high-grade glioma (HGG) from low-grade glioma (LGG). Moreover, (68)Ga-PRGD2 PET/CT showed different accumulation patterns for HGG of WHO grades III and IV. This is the first noninvasive integrin imaging study, to the best of our knowledge, conducted in preoperative patients with different grades of glioma, and it preliminarily indicated the effectiveness of this novel method for evaluating glioma grading and demarcation.

2014Nov
Workplace Health Saf
Workplace Health Saf 2014 Nov 11;62(11):447-55. Epub 2014 Aug 11.

Excessive workload from employment and household duties may negatively affect married female nurses' health. This study explored job stress, family stress, social support, and health status among married female nurses to identify predictors of nurses' health status. Using a cross-sectional design, 233 married female nurses were recruited from two regional teaching hospitals.Read More

The results showed that working hours per week, job stress, and overcommitment to their jobs were significant determinants of health status. Based on study findings, nursing supervisors should avoid scheduling nurses to work more than 48 hours per week. Job stress adjustment courses could enable nurses to relax after work, avoiding overcommitment. [Workplace Health Saf 2014;62(11):447-452.].

Activation of the BTLA-HVEM co-inhibitory signaling pathway impairs antitumor immunity. Our previous study demonstrated that the extracellular domain of murine BTLA (the soluble form of BTLA) can facilitate HSP70 vaccine-triggered antitumor immunity by blocking BTLA-HVEM interactions in a murine TC-1 non-metastatic tumor model. However, it is unknown whether this strategy has beneficial effects on highly malignant metastatic tumors, such as melanoma.Read More

To address this question, we expressed the soluble form of BTLA (sBTLA) in combination with HSP70 vaccine and examined the resulting antitumor activity in a melanoma pulmonary metastasis model. A recombinant adeno-associated virus (AAV) vector was used for the sBTLA gene delivery because of its high transfection efficiency and low toxicity. In vitro expression of AAV-sBTLA enhanced lymphocyte activation and induced specific cytotoxicity against B16F1 murine melanoma cells, while in vivo administration of AAV-sBTLA plus HSP70 vaccine by tail vein injection exerted a limited, late-stage antitumor effect against the existing B16F1 cells. However, the combination treatment generated a potent prophylactic antitumor response in the melanoma lung metastasis model in B6 mice. In this case, most of the metastatic foci were inhibited, and mouse survival was prolonged. Furthermore, the Th1 cytokines IL-2 and IFN-γ were up-regulated, while the negative regulatory molecules IL-10 and TGF-β were down-regulated. The number of regulatory T cells also decreased in the tumor environment. Therefore, AAV-sBTLA plus HSP70 vaccine may have therapeutic potential for the prevention of metastatic melanoma.

Bonding stability of resinous adhesives to dentin is still problematic and may involve regional variations in dentin composition. This study is to evaluate the effect of dentin depth on the stability of resin-dentin bonds under thermocycling challenge.
Dentin slabs with two flat surfaces parallel to the tooth axis were obtained from extracted human third molars.Read More

The slabs were randomized into eight groups according to the location of dentin [deep dentin (DD) or superficial dentin (SD)], the adhesive treatment (Single Bond 2 or Clearfil S(3) Bond), and the storage treatment (thermocycling for 5000 times vs. no). After the adhesive treatment and composite buildup on the dentin slabs, the micro-shear bond strength (μSBS) of each group was detected. The concentrations of cross-linked carboxyterminal telopeptide of type I collagen (ICTP) were also evaluated using an immunoassay to detect the degree of collagen degradation in each group.
Dentin depth, adhesive treatment and storage treatment all showed significant effects on both the μSBSs and the ICTP values (P<0.05). Regardless of the adhesive type, thermocycling decreased the μSBSs and increased the ICTP values (P<0.05). The DD groups showed significantly lower μSBSs and higher ICTP values than SD groups after thermocycling aging (P<0.05). The treatment with Single Bond 2 significantly increased the ICTP values (P<0.05), whereas Clearfil S(3) Bond showed no effect on the ICTP values (P>0.05).
Deep dentin showed significantly more bond degradation after thermocycling than did superficial dentin.

Human serum albumin (HSA) is a cysteine rich molecule that is most abundant in human blood plasma. To remain viable in the market due to lower marketing costs for HSA, it is important to produce a large quantity in an economical manner by recombinant technology. The objective of this study was to maximize recombinant HSA (rHSA) production using a Mut(s) Pichia pastoris strain by fermentation process optimization.Read More

We evaluated the impact of process parameters on the production of rHSA, including induction cell density (wet cell weight, g/L) and the control of specific growth rate at induction. In this study, we demonstrated that induction cell density is a critical factor for high level production of rHSA under controlled specific growth rate. We observed higher specific productivities at higher induction cell densities (285 g/L) and at lower specific growth rates (0.0022-0.0024/h) during methanol induction phase, and achieved the broth titer of rHSA up to 10 g/L. The temperature shift from 24 to 28(o) C was effective to control the specific growth rate at low level (≤0.0024/h) during methanol induction phase while maintaining high specific productivity [0.0908 mgrHSA /(gwcw h)]. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 30:1488-1496, 2014.

Programmed cell death-1 (PD-1) is involved in hepatitis B virus (HBV) infection and single-nucleotide polymorphism (SNP) rs10204525 in the 3'-untranslated region (3' UTR) of PD1 gene was shown to be associated with the disease course of HBV infection. This study examined the associations of PD-1 mRNA expression with the clinical and viral profiles and the genotypes of rs10204525 in HBV infection. PD-1 mRNA levels in peripheral blood nuclear cells were determined by real-time quantitative reverse transcription polymerase chain reaction (PCR).Read More

PD1 rs10204525 was genotyped by bidirectional PCR amplification of specific alleles. The results showed that patients with chronic HBV infection had significantly elevated PD-1 mRNA levels than healthy controls. Patients with chronic hepatitis and hepatocellular carcinoma had significantly higher PD-1 mRNA levels than healthy controls. HBeAg (+) patients had significantly higher PD-1 mRNA levels than HBeAg (-) patients (P<0.001). PD-1 mRNA levels were sequentially increased with the elevation of HBV DNA levels. In HBV patients, but not in healthy controls, PD-1 mRNA levels were sequentially decreased from rs10204525 genotypes AA, AG to GG and the levels in genotype AA were significantly higher than in genotype GG (P=0.039). These findings suggest that increased PD-1 expression may affect the disease course of chronic HBV infection by facilitating HBV viral replication, and this may at least partially relate to PD1 3' UTR polymorphism.

The aim of this study was to investigate the role of co-stimulatory molecule B7-H1 in gastric carcinoma, to assess its clinical significance, and to explore related mechanism. Expression of B7-H1 and interferon gamma (IFN-γ) was evaluated by immunohistochemistry in 205 gastric carcinoma tissues and nonmalignant para-carcinoma tissues and 30 normal tissues. Expression data were correlated with clinicopathologic features of the patients.Read More

Furthermore, gastric carcinoma cell line SGC7901, MGC803, and AGS were employed to assess the expression of B7-H1 under the stimulation of IFN-γ. There was no detectable or weak amount of B7-H1 in normal tissue, while 43 % (88/205) of gastric carcinoma tissues and nonmalignant para-carcinoma tissues were confirmed with B7-H1 positive (p < 0.01). High B7-H1 expression was significantly associated with the age (p < 0.01), alcohol (p < 0.05), carcinoma location (p < 0.01), and differentiation (p < 0.05). Moreover, IFN-γ and CD3(+) T cells infiltration were found in carcinoma tissues, but not in normal tissues. In addition, the expression of B7-H1 was also found in gastric carcinoma cell lines (SGC7901, MGC803 and AGS), and IFN-γ could increase its expression. Our data suggest that B7-H1 may represent a new early diagnostic marker for patients with well-differentiated gastric carcinoma. Furthermore, given its immune-inhibitory function, B7-H1 may represent a potential target in the treatment of gastric carcinoma.

CDKN3 (cyclin-dependent kinase inhibitor 3), a dual specificity protein phosphatase, dephosphorylates cyclin-dependent kinases (CDKs) and thus functions as a key negative regulator of cell cycle progression. Deregulation or mutations of CDNK3 have been implicated in various cancers. However, the role of CDKN3 in Bcr-Abl-mediated chronic myelogenous leukemia (CML) remains unknown.Read More

Here we found that CDKN3 acts as a tumor suppressor in Bcr-Abl-mediated leukemogenesis. Overexpression of CDKN3 sensitized the K562 leukemic cells to imanitib-induced apoptosis and dramatically inhibited K562 xenografted tumor growth in nude mouse model. Ectopic expression of CDKN3 significantly reduced the efficiency of Bcr-Abl-mediated transformation of FDCP1 cells to growth factor independence. In contrast, depletion of CDKN3 expression conferred resistance to imatinib-induced apoptosis in the leukemic cells and accelerated the growth of xenograph leukemia in mice. In addition, we found that CDKN3 mutant (CDKN3-C140S) devoid of the phosphatase activity failed to affect the K562 leukemic cell survival and xenografted tumor growth, suggesting that the phosphatase of CDKN3 was required for its tumor suppressor function. Furthermore, we observed that overexpression of CDKN3 reduced the leukemic cell survival by dephosphorylating CDK2, thereby inhibiting CDK2-dependent XIAP expression. Moreover, overexpression of CDKN3 delayed G1/S transition in K562 leukemic cells. Our results highlight the importance of CDKN3 in Bcr-Abl-mediated leukemogenesis, and provide new insights into diagnostics and therapeutics of the leukemia.

Vascular cognitive impairment, no dementia (VCIND) is a condition at risk for future dementia and should be the target of preventive strategies. Preliminary evidence suggests that acupuncture may be a clinically effective intervention for people with early-stage vascular cognitive impairment. We will do a multicenter, 6-month, drug-controlled, nonblinded, randomized, parallel-group trial to determine whether acupuncture is effective for improving cognitive function and quality of life for patients with VCIND.Read More


A total of 216 eligible patients will be recruited and randomly assigned acupuncture for two sessions/week (n = 108) or citicoline 300 mg/day (n = 108) in a multicenter, 6-month trial. The primary endpoint is cognition (Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-cog)). Secondary endpoints include assessments of activities of daily living and behavioral symptoms (Clock Drawing Test (CDT), Activities of Daily Living (ADL) and Instrumental Activities of Daily Living scale (IADL)).
This will be the first large-scale trial specifically evaluating acupuncture therapy in VCIND. If the study confirms the effectiveness and safety of acupuncture treatment, it will be important to examine how the acupuncture approach could most effectively be integrated into the provision of routine healthcare.
This study is registered as an International Standard Randomised Controlled Trial on 17 January 2014, number ISRCTN 82980206.

Sclerosing epithelioid fibrosarcoma (SEF) is a clinicopathologically distinct variant of fibrosarcoma that is capable of recurrence and metastasis. Awareness of imaging features and histopathologic characteristics will be helpful for differential diagnosis from other common tumors. Here, we report a case of SEF metastasizing to the pancreas as a solitary mass mimicking primary pancreatic cancer, and summarize the reported cases with FDG PET/CT from the literature (n=4).Read More

PET/CT showed abnormal FDG accumulation (n=2), mild FDG uptake (n=1), or photopenic (n=1). The FDG PET/CT features are closely related to histopathologic characteristics regarding its differentiation and aggressiveness.

Osteoporosis (OP) is a common bone disease, which adversely affects life quality. Effective treatments are necessary to combat both the loss and fracture of bone. Recent studies indicated that caffeic acid phenethyl ester (CAPE) is a natural chemical compound from honeybee propolis which is capable of attenuating osteoclastogenesis and bone resorption.Read More

Therefore, this study aimed to investigate the effect of CAPE on bone loss in OP mice using micro-computed tomography (CT) and histology.
Eighteen mice were prepared and evenly divided into three groups. The six mice in the sham+PBS group did not undergo ovariectomy and were intraperitoneally injected with PBS during the curing period. Twelve mice were ovariectomized (OVX) to induce OP. Six of them in the OVX+CAPE group were intraperitoneally injected with 0.5 mg/kg CAPE twice per week for 4 weeks after ovariectomy. The other six OVX mice in OVX+PBS group were treated with PBS. All the mice were sacrificed 4 weeks after ovariectomy. The tibias were bilaterally excised for micro-CT scan and histological analysis. The Mann-Whitney U test was used to test the statistical differences among groups.
Bone loss occurred in OVX mice. Compared with the sham+PBS group, mice in the OVX+PBS group exhibited a significant decrease in bone mineral density (BMD, P < 0.05), bone volume fraction (BV/TV, P < 0.01), trabecular thickness (Tb.Th, P < 0.05), and trabecular number (Tb.N, P < 0.01), as well as a non-insignificant increase in the number of osteoclasts (N.Oc/B.Pm). With CAPE treatment, the microarchitecture of the tibial metaphyses was significantly improved with a reduction of osteoclast formation. Compared with the OVX+PBS group, BV/TV in the OVX+CAPE group was significantly increased by 33.9% (P < 0.05).
CAPE therapy results in the protection of bone loss induced by OVX.

BackgroundThe Hedgehog (Hh) signaling pathway has been implicated in stem cell maintenance and its activation is aberrant in several types of cancer including mesothelioma. Protein kinase CK2 affects several cell signaling pathways through the mechanism of phosphorylation.MethodsProtein and mRNA levels of CK2¿ and Gli1 were tested by quantitative RT-PCR and immunohistochemistry staining in mesothelioma samples and cell lines.Read More

Down-regulated Gli1 expression and transcriptional activity were demonstrated by RT-PCR, Western blot and luciferase reporter assay.ResultsIn this study, we show that CK2¿ is over-expressed and a positive regulator of Hegdehog/Gli1 signaling in human malignant pleural mesothelioma. First of all, we found that the mRNA levels of CK2¿ and Gli1 were broadly elevated and correlated (n¿=¿52, r¿=¿0.401, P¿<¿0.05), compared with LP9 (a normal mesothelial cell line). We then investigated their expression at the protein level, and found that all the 7 mesothelioma cell lines tested showed positive staining in CK2¿ and Gli1 immunohistochemistry. Correlation analysis by Pearson test for CK2¿ and Gli1 expression in the 75 mesothelioma tumors and the 7 mesothelioma cell lines showed that the two protein expression was significantly correlated (n¿=¿82, r¿=¿0.554, P¿<¿0.01). Furthermore, we demonstrated that Gli1 expression and transcriptional activity were down-regulated after CK2¿ was silenced in two mesothelioma cell lines (H28 and H2052). CK2¿ siRNA also down-regulated the expression of Hh target genes in these cell lines. Moreover, treatment with a small-molecule CK2¿ inhibitor CX-4945 led to dose-dependent inhibition of Gli1 expression and transcriptional activity. Conversely, forced over-expression of CK2¿ resulted in an increase in Gli1 transcriptional activity in H28 cells.ConclusionsThus, we report for the first time that over-expressed CK2¿ positively regulate Hh/Gli1 signaling in human mesothelioma.

2014Nov

Receptor recognition by viruses is the first and essential step of viral infections of host cells. It is an important determinant of viral host range and cross-species infection, and a primary target for antiviral intervention. Coronaviruses recognize a variety of host receptors, infect many hosts, and are health threats to humans and animals.Read More

The receptor-binding S1 subunit of coronavirus spike proteins contains two distinctive domains, N-terminal domain (S1-NTD) and C-terminal domain (S1-CTD), both of which can function as receptor-binding domains (RBDs). S1-NTDs and S1-CTDs from three major coronavirus genera recognize at least four protein receptors and three sugar receptors, and demonstrate a complex receptor recognition pattern. For example, highly similar coronavirus S1-CTDs within the same genus can recognize different receptors, whereas very different coronavirus S1-CTDs from different genera can recognize the same receptor. Moreover, coronavirus S1-NTDs can recognize either protein or sugar receptors. Structural studies in the past decade have elucidated many of the puzzles associated with coronavirus-receptor interactions. This article reviews the latest knowledge on the receptor recognition mechanisms of coronaviruses, and discusses how coronaviruses have evolved their complex receptor recognition pattern. It also summarizes important principles that govern receptor recognition by viruses in general.

This study aimed to investigate the potential use of icotinib as first-line treatment to prevent brain metastasis from advanced lung adenocarcinoma.
This investigation was designed as a retrospective nonrandomized controlled study. Enrolled patients received either icotinib or traditional chemotherapy as their first-line treatment.Read More

The therapeutic efficacy was compared among patients with advanced (stages IIIB and IV) lung adenocarcinoma with epidermal growth factor receptor (EGFR)-sensitive mutation. The primary endpoint was the cumulative incidence of brain metastasis, whereas the secondary endpoint was overall survival (OS). Death without brain metastasis was considered a competitive risk to calculate the cumulative risk of brain metastasis. Survival analysis was conducted using the Kaplan-Meier method and statistical significance were determined using the log-rank test.
The present study included 396 patients with 131 in the icotinib group and 265 in the chemotherapy group. Among those with EGFR-sensitive mutation, the cumulative risk of brain metastasis was lower in the icotinib group than in the chemotherapy group. However, no significant difference in OS was observed between the two groups.
Icotinib can effectively reduce the incidence of brain metastasis and therefore improve prognosis in advanced lung adenocarcinoma patients with EGFR-sensitive mutation.

Sodium houttuyfonate (SH) has been found to be mildly anti-pathogenetic against the planktonic and biofilm phenotypes of Pseudomonas aeruginosa. Here, we have attempted to investigate further the anti-pathogenicity of SH and EDTA-Na2 in combination and in vitro and in vivo against planktonic and biofilm phenotypes of Pseudomonas aeruginosa (16 strains), Staphylococcus aureus (13 strains) and Candida albicans (13 strains). The antimicrobial activity of SH against all three pathogens increased dramatically when it was combined with EDTA-Na2, in vitro.Read More

Toxic reactions to the drugs when administered orally were insignificant in mice; no abnormalities were observed in the internal organs, such as the lungs and kidneys. Finally, the results of in vivo studies indicate that SH could extend the lifespan of infected animals when administered in combination with EDTA-Na2. Therefore, the results of the present study lead us to suggest that SH could be a promising antimicrobial agent and that SH combined with EDTA-Na2 has the potential to be an excellent choice of drug for combating bacterial infections clinically.

2014Oct

One hundred isolates of Aspergillus fumigatus sensu lato mainly from China, as well as from Australia, France, India, Indonesia, Ireland, UK, and USA were analyzed to infer their sequence types (STs) and population diversity based on partial calmodulin, calcineurin regulatory subunit B, beta-tubulin, cytochrome C and calcineurin catalytic subunit A genes as well as their mating types, using ClonalFrame, Structure and MEGA software. Our results inferred 48 STs and showed that most of the STs or lineages evolved independently and without clear population structure among them. Whereas one lineage was recognized that could be a true population and in which one clade might diverge into another distinct lineage, namely, a cryptic species, A.Read More

neoellipticus. In addition, we found that mutation, parasexual, and sexual recombination could, respectively, play specific roles in the evolution of these fungi. Our results also showed that MAT1-1/MAT1-2 mating type ratios of A. fumigatus sensu lato was biased to nearly 1:1.4 (20/28) when clone-corrected, but when not clone-corrected, the ratio of MAT1-1/MAT1-2 was so biased as near 1:2 (35/65), which might mean that isolates with MAT1-2 are in the process of losing sexual ability preceding those with MAT1-1.

2014Oct
IEEE Trans Image Process
IEEE Trans Image Process 2014 Oct 7;23(10):4242-54. Epub 2014 Aug 7.

In this paper, we extend an existing universal variational framework for image inpainting with new numerical algorithms. Given certain regularization operator Φ and denoting u the latent image, the basic model is to minimize the l(p), (p=0,1) norm of Φu preserving the pixel values outside the inpainting region. Utilizing the operator splitting technique, the original problem can be approximated by a new problem with extra variable.Read More

With the alternating minimization method, the new problem can be decomposed as two subproblems with exact solutions. There are many choices for Φ in our approach such as gradient operator, wavelet transform, framelet transform, or other tight frames. Moreover, with slight modification, we can decouple our framework into two relatively independent parts: 1) denoising and 2) linear combination. Therefore, we can take any denoising method, including BM3D filter in the denoising step. The numerical experiments on various image inpainting tasks, such as scratch and text removal, randomly missing pixel filling, and block completion, clearly demonstrate the super performance of the proposed methods. Furthermore, the theoretical convergence of the proposed algorithms is proved.

Pregnane X receptor (PXR) is a member of nuclear receptor superfamily and responsible for the detoxification of xenobiotics. Our previously study demonstrated that PXR is expressed in endothelial cells (ECs) and acts as a master regulator of detoxification genes to protect ECs against xenobiotics. Vascular endothelial cells are key sentinel cells to sense the pathogens and xenobiotics.Read More

In this study, we examined the potential function of PXR in the regulation of innate immunity in vasculatures. Treatments with PXR agonists or overexpression of a constitutively active PXR in cultured ECs increased gene expression of the key pattern recognition receptors, including Toll-like receptors (TLR-2, -4, -9) and NOD-like receptors (NOD-1 and -2 and NLRP3). In particular, PXR agonism triggered the activation of NLRP3 inflammasome and the ensuing cleavage and maturation of caspase-1 and interleukin-1β (IL-1β). Conversely, selective antagonism or gene silencing of PXR abrogated NLRP3 inflammasome activation. In addition, we identified NLRP3 as a transcriptional target of PXR by using the promoter-reporter and ChIP assays. In summary, our findings revealed a novel regulatory mechanism of innate immune by PXR, which may act as a master transcription factor controlling the convergence between the detoxification of xenobiotics and the innate immunity against them.

Fibroblast activation is one of the most important mechanisms for Angiotensin II (Ang II) in promoting renal fibrosis. Transcription factor Ets-1 is recognized to play a key role in kidney diseases. However, the role and mechanisms of Ets-1 in Ang-II induced fibroblast activation and kidney fibrosis are not fully understood.Read More


Mice were treated with Ang II via osmotic mini-pumps or Ang II expression plasmid (pAng II). Cultured normal rat kidney interstitial fibroblast (NRK-49F) cells were incubated with Ang II. Role of Ets-1 in renal fibrosis and fibroblast activation were assessed by Western blot, Immunohistochemical staining'MTT, Boyden chamber and Immunofluorescence staining. Effects of miR-221 on Ets-1 and fibroblast activation were investigated by MTT, Boyden chamber, Western blot and Q-PCR.
We found that Ets-1 was up-regulated in fibrotic kidneys. Similarly, Ang II could activate NRK-49F cells as demonstrated by up-regulated α-SMA and fibronectin(FN) expression and enhanced cell proliferation and migration. Ang II also induced Ets-1 expression in NRK-49F cells in a dose and time dependent manner. Knock-down of Ets-1 by RNA interference attenuated Ang II-induced activation of NRK-49F cells. Ets-1 was previously reported as a target of microRNA-221 (miR-221). In Ang II-induced fibrotic kidney, miR-221 was down-regulated. Similar results were observed in Ang II treated NRK-49F cells. Ectopic expression of miR-221 mimic attenuated the up-regulation of Ets-1 by Ang II in NRK-49F cells, which further prevented the activation of NRK-49F cells. However, the inhibitor of miR-221 aggravated Ang II induced Ets-1 expression and NRK-49F cells activation.
Our study suggests that miR-221/Ets-1 axis takes an important role in mediating AngII induced interstitial fibroblast activation and renal fibrosis.

The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) is currently spreading among humans, making development of effective MERS vaccines a high priority. A defined receptor-binding domain (RBD) in MERS-CoV spike protein can potentially serve as a subunit vaccine candidate against MERS-CoV infections. To identify an ideal vaccine candidate, we have constructed five different versions of RBD fragments, S350-588-Fc, S358-588-Fc, S367-588-Fc, S367-606-Fc, and S377-588-Fc (their names indicate their residue range in the spike protein and their C-terminal Fc tag), and further investigated their receptor binding affinity, antigenicity, immunogenicity, and neutralizing potential.Read More

The results showed that S377-588-Fc is among the RBD fragments that demonstrated the highest DPP4-binding affinity and induced the highest-titer IgG antibodies in mice. In addition, S377-588-Fc elicited higher-titer neutralizing antibodies than all the other RBD fragments in mice, and also induced high-titer neutralizing antibodies in immunized rabbits. Structural analysis suggests that S377-588-Fc contains the stably folded RBD structure, the full receptor-binding site, and major neutralizing epitopes, such that additional structures to this fragment introduce non-neutralizing epitopes and may also alter the tertiary structure of the RBD. Taken together, our data suggest that the RBD fragment encompassing spike residues 377-588 is a critical neutralizing receptor-binding fragment and an ideal candidate for development of effective MERS vaccines, and that adding non-neutralizing structures to this RBD fragment diminishes its neutralizing potential. Therefore, in viral vaccine design, it is important to identify the most stable and neutralizing viral RBD fragment, while eliminating unnecessary and non-neutralizing structures, as a means of "immunofocusing".

BackgroundCervical lesions caused by integrated human papillomavirus (HPV) infection are highly dangerous because they can quickly develop into invasive cancers. However, clinicians are currently hampered by the lack of a quick, convenient and precise technique to detect integrated/mixed infections of various genotypes of HPVs in the cervix. This study aimed to develop a practical tool to determine the physical status of different HPVs and evaluate its clinical significance.Read More

MethodsThe target population comprised 1162 women with an HPV infection history of¿>¿six months and an abnormal cervical cytological finding. The multiple E1-L1/E6E7 ratio analysis, a novel technique, was developed based on determining the ratios of E1/E6E7, E2/E6E7, E4E5/E6E7, L2/E6E7 and L1/E6E7 within the viral genome. Any imbalanced ratios indicate integration. Its diagnostic and predictive performances were compared with those of E2/E6E7 ratio analysis. The detection accuracy of both techniques was evaluated using the gold-standard technique ¿detection of integrated papillomavirus sequences¿ (DIPS). To realize a multigenotypic detection goal, a primer and probe library was established.ResultsThe integration rate of a particular genotype of HPV was correlated with its tumorigenic potential and women with higher lesion grades often carried lower viral loads. The E1-L1/E6E7 ratio analysis achieved 92.7% sensitivity and 99.0% specificity in detecting HPV integration, while the E2/E6E7 ratio analysis showed a much lower sensitivity (75.6%) and a similar specificity (99.3%). Interference due to episomal copies was observed in both techniques, leading to false-negative results. However, some positive results of E1-L1/E6E7 ratio analysis were missed by DIPS due to its stochastic detection nature. The E1-L1/E6E7 ratio analysis is more efficient than E2/E6E7 ratio analysis and DIPS in predicting precancerous/cancerous lesions, in which both positive predictive values (36.7%-82.3%) and negative predictive values (75.9%-100%) were highest (based on the results of three rounds of biopsies).ConclusionsThe multiple E1-L1/E6E7 ratio analysis is more sensitive and predictive than E2/E6E7 ratio analysis as a triage test for detecting HPV integration. It can effectively narrow the range of candidates for colposcopic examination and cervical biopsy, thereby lowering the expense of cervical cancer prevention.

The Agaricus brasiliensis proves to be the main source of many minerals, especially selenium (Se). In this study, Se-containing polysaccharides and proteins were isolated, purified, and characterized. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical scavenging activity of Se-containing proteins and polysaccharides were also studied.Read More

Selenium in A. brasiliensis is present mostly in organic forms, accounting for 81.57% of the total Se. The organic forms of selenium mainly present in Se proteins account for 73.53%, while 12.23% is in Se polysaccharides. Two Se-containing proteins (AB-SePA-22) and (AB-SePG-22) with Se contents of 4.935 µg/g and 6.083 µg/g were obtained. AB-SePA-22 appeared as four bands with molecular masses of 16.7, 21.7, 26.3, and 33.6 kDa, respectively. The Se content of the three Se-containing polysaccharides, namely AB-SeP-1, AB-SeP-2, and AB-SeP-3, were 1.911, 0.613, and 0.671 µg/g, respectively. AB-SeP-1 (3.1×103 Da) was composed of glucose and galactose in a 7.494:1 molar ratio, whereas AB-SeP-2 (2.1×104 Da and 3.5×104 Da) and AB-SeP-3 (1.1×105 Da) were composed of glucose, galactose, and mannose with molar ratios of 27.01:1.55:1 and 9.805:1:1.22, respectively. Moreover, crude Se polysaccharide and total soluble Se protein had good antioxidant activities on scavenging DPPH and hydroxyl radical, and further research is needed.

In this work, chemiluminescence (CL) reagent and catalyst metal ion complexes bifunctionalized gold nanoparticles (BF-AuNPs) with high CL efficiency were synthesized via an improved synthesis strategy. Biothiols, such as cysteine (Cys), cysteinyl-glycine (Cys-Gly), homocysteine (Hcy), and glutathione (GSH), instead of 2-[bis[2-[carboxymethyl-[2-oxo-2-(2-sulfanylethylamino)ethyl]amino]ethyl]amino]acetic acid (DTDTPA), were used as new chelators. N-(aminobutyl)-N-(ethylisoluminol) (ABEI) was used as a model of CL reagents and Cu(2+) as a model of metal ion.Read More

In this strategy, biothiols were first grafted on the surface of ABEI-AuNPs by Au-S bond. Then, Cu(2+) was captured onto the surface of ABEI-AuNPs by the coordination reaction to form BF-AuNPs. The CL intensity of Cu(2+)-Cys/ABEI-AuNPs was 1 order of magnitude higher than that of DTDTPA/Cu(2+)-ABEI-AuNPs synthesized by the previous work. Moreover, strong CL emission of Cu(2+)-Cys/ABEI-AuNPs was also observed in neutral pH conditions. In addition, the present BF-AuNPs synthesis method exhibited advantages over the previous method in CL efficiency, simplicity, and synthetic rate. Finally, by virtue of Cu(2+)-Cys/ABEI-AuNPs as a platform, a simple CL chemosensor for the sensitive and selective detection of pyrophosphate ion (PPi) was established based on the competitive coordination interactions of Cu(2+) between Cys and PPi. The method exhibited a wide detection range from 10 nM to 100 μM, with a low detection limit of 3.6 nM. The chemosensor was successfully applied to the detection of PPi in human plasma samples. It is of great application potential in clinical analysis. This work reveals that BF-AuNPs could be used as ideal nanointerface for the development of novel analytical methods.

Silks spun by silkworms and spiders feature outstanding mechanical properties despite being spun under benign conditions. The superior physical properties of silk are closely related to its complicated hierarchical structures constructed from nanoscale building blocks, such as nanocrystals and nanofibrils. Here, we report a novel silk dissolution behavior, which preserved nanofibrils in CaCl2-formic acid solution, that enables spinning of high-quality fibers with a hierarchical structure.Read More

This process is characterized by simplicity, high efficiency, low cost, environmental compatibility and large-scale industrialization potential, as well as having utility and potential for the recycling of silk waste and the production of silk-based functional materials.

Coronary artery fistula (CAF) and noncompaction of the ventricular myocardium (NCVM) result from obliteration or compact failure of the intramyocardial trabecular sinusoids to form a ventricular cavity wall. The draining site of a right coronary artery (RCA) fistula may usually be the right ventricle, right atrium, or pulmonary artery. An RCA aneurysm with a fistula to the left ventricle is rare.Read More

We report a patient with an RCA aneurysm with a fistula to the left ventricle coexisting with NCVM. The patient's condition was diagnosed by echocardiography and contrast-enhanced multidetector computed tomography.

This article has been retracted by the Editorial Board of INDUSTRIAL HEALTH due to violation of our publishing policies and procedures as of September 26, 2014.Read More

A novel immunosensor for α-1-fetoprotein based on dialdehyde cellulose/ionic liquid composite film as a matrix has been developed. Microcrystalline cellulose was activated by sodium metaperiodate to produce dialdehyde cellulose. Antibodies can be immobilized on the electrode by a one-step method through covalent bonding of the aldehyde groups of dialdehyde cellulose with the amino groups of antibodies, in which no additional chemical cross-linking step is required.Read More

Moreover, ionic liquid added can improve the conductivity of the sensing interface and, therefore, can enhance the electrochemical signal. In this work, α-1-fetoprotein was detected within the range from 0.1 to 60ngml(-1) with a detection limit of 0.07ngml(-1) (signal/noise=3). The proposed immunosensor had good specificity and reproducibility. It was used to determine real samples with satisfactory results.

Available tools in liver surgery planning rely on the future remnant liver (FRL) volume. Inappropriate decision might be made since the same FRL volume might represent different liver functions depending on the severity of underlying liver damage. This study developed an alternative system to estimate FRL function and to predict the risk of postoperative liver failure.Read More


Current study recruited 71 prehepatectomy patients and 71 healthy volunteers. A technetium-99-labelled asialoglycoproteins was given to participants and SPECT was used to capture the intensity of the signal, represented by uptake index (UI). The agreement between preoperative UI values, liver function tests, and Child scores were evaluated. Linear regression was used to evaluate the agreement between predicted UI for FRL and postoperative UI values. Area under the receiver operating characteristic (AUC) curve was used to evaluate the discriminative performance of UI in differentiating patient with high risk of liver failure.
Preoperative UIs are highly correlated with Child score (P < 0.0001), especially to identify patients with ascites and elevated bilirubin. The predicted UIs were in close agreement with the actual postoperative UI values (r = 0.95 P < 0.001). The AUC analysis indicated that UI values had a high accuracy in predicting the risk of liver failure (AUC = 0.95, P < 0.0001). The best cut-off point was 0.9 and the corresponding sensitivity was 100 % and specificity was 92 %.
The new methodology reliably estimates FRL function and predicts the risk of liver failure. It provides a visual aid for liver surgeon in surgery planning and risk assessment.

MicroRNAs (miRNAs) are small ribonucleotides regulating gene expression. MicroRNAs are present in the blood in a remarkably stable form and have emerged as potential diagnostic markers in patients with cardiovascular disease. Our study aimed to assess circulating miR-133a levels in MHD patients and the relation of miR-133a to cardiac hypertrophy.Read More


We profiled miRNAs using RNA isolated from the plasma of participants. The results were validated in 64 MHD patients and 18 healthy controls.
Levels of plasma miR-133a decreased in MHD patients with LVH compared with those in healthy controls. Plasma miR-133a concentrations were negatively correlated with LVMI and IVS. After single hemodialytic treatment, plasma miR-133a levels remained unchanged. Cardiac Troponin I and T were not associated with LVMI and IVS.
Our observations supplied the possibility that circulating miR-133a could be a surrogate biomarker of cardiac hypertrophy in MHD patients.

The eukaryotic calcineurin (CN) pathway comprising catalytic A (CnA) and regulatory B subunits (CnB) is crucial for many biological processes but functionally unexplored in entomopathogenic fungi. Here, we characterise three CN subunits (CnA1, CnA2 and CnB) and a downstream CN-responsive zinc finger transcription factor (Crz1) in Beauveria bassiana. CN-mediated phosphatase activity decreased by 16-38 % in all deletion mutants compared with wild type.Read More

Growth and conidiation were most defective in ΔcnB, which showed a large proportion of abnormally branched germlings but were less defective in ΔcnA1 and ΔcnA2. Conidiation defects also occurred in Δcrz1, uniquely accompanied with slower germination. Compared with wild type, the four deletion mutants became, to varying degrees, more sensitive to Ca(2+), Mn(2+), Zn(2+), Mg(2+), two oxidants, three cell wall stressors, carbendazim, heat shock and ultraviolet (UV)-B irradiation. They were also less virulent to Spodoptera litura larvae. Only ΔcnB and Δcrz1 were less tolerant to high osmolarity. The altered phenotypes of the deletion mutants were associated with lower intracellular mannitol and trehalose levels, reduced overall activity of superoxide dismutases and catalases, altered cell wall composition and down-regulation of numerous phenotype-influencing genes. Additionally, the transcription of six cascaded genes in two stress-responsive mitogen-activated protein kinase (MAPK) pathways and the phosphorylation of hallmarking Hog1 and Slt2 were largely down-regulated in all the deletion mutants under osmotic and cell wall stresses, respectively. All the changes were restored by gene complementation. Taken together, three calcineurin subunits and Crz1 play vital, but variable, roles in B. bassiana responses to environmental stresses during development and host signals during infection.

White spot syndrome virus (WSSV) is one of the major pathogens of cultured shrimp. Identification of envelope protein interactions has become a central issue for the understanding of WSSV assembly. In this paper, WSSV envelope protein VP52B was fused with GST-tag and expressed in Escherichia coli BL-21(DE3).Read More

Immunogold-electron microscopy revealed that VP52B was located on the outside surface of WSSV virions. Far-Western blotting analysis suggested that VP52B might directly interact with a major viral envelope protein VP26, and their interaction was confirmed by GST pull-down assay. Further investigation showed that the VP52B binding domain was located between residues 135-170 of VP26. These findings will enhance our understanding of the molecular mechanisms of WSSV morphogenesis.

BackgroundChina, like other countries, is facing a growing burden of chronic disease but the prevalence of multimorbidity and implications for the healthcare system have been little researched. We examined the epidemiology of multimorbidity in southern China in a large representative sample. The effects of multimorbidity and other factors on usual source of healthcare were also examined.Read More

MethodsWe conducted a large cross-sectional survey among approximately 5% (N =162,464) of the resident population in three prefectures in Guangdong province, southern China in 2011. A multistage, stratified random sampling was adopted. The study population had many similar characteristics to the national census population. Interviewer-administered questionnaires were used to collect self-report data on demographics, socio-economics, lifestyles, healthcare use, and health characteristics from paper-based medical reports.ResultsMore than one in ten of the total study population (11.1%, 95% confidence interval (CI) 10.6 to 11.6) had two or more chronic conditions from a selection of 40 morbidities. The prevalence of multimorbidity increased with age (adjusted odds ratio (aOR) =1.36, 95%CI 1.35 to 1.38 per five years). Female gender (aOR =1.70, 95%CI 1.64 to 1.76), low education (aOR =1.26, 95%CI 1.23 to 1.29), lack of medical insurance (aOR =1.79, 95%CI 1.71 to 1.89), and unhealthy lifestyle behaviours were independent predictors of multimorbidity. Multimorbidity was associated with the regular use of secondary outpatient care in preference to primary care.ConclusionsMultimorbidity is now common in China. The reported preferential use of secondary care over primary care by patients with multimorbidity has many major implications. There is an urgent need to further develop a strong and equitable primary care system.

To investigate the potential immunomodulatory properties of fetal bone marrow derived mesenchymal stem cells (FBM- MSCs).
Mononuclear cells from the bone marrow of second trimester (14-22 wks) fetus were isolated and cultured for the derivation of MSCs. The derived FBM-MSC cells were characterized via morphology, immunophenotyping and the adipogenic and osteogenic differentiation assays.Read More

The immunomodulatory properties of FBM-MSC on lymphocytes were evaluated through the co- culture assay with PHA activated adult peripheral blood mononuclear cells (PBMCs).
Derived FBM-MSCs were CD29⁺, CD44⁺, CD49e⁺, CD73⁺, CD90⁺, CD105⁺ and CD31⁻ , CD34⁻ , CD45⁻ , HLA-DR⁻ and can be differentiated into adipocytes and osteocytes. When co-cultured with PHA-activated PBMCs, FBM-MSCs inhibited the proliferation of lymphocytes up to 96% and down-regulated the secretion of inflammatory cytokines such as IFN-γ and TNF-α up to 90.9% and 58.4% respectively. When compared with FBM-MSCs cultured alone, the expression of MSCs derived immunomodulatory cytokines, such as IDO, TSG-6 and TGF-β, was up-regulated significantly in the co-culture system.
MSC derived from fetal bone marrow demonstrated immunosuppressive effects on adult PBMCs in vitro. MSC-derived cytokines like IDO, TSG-6 and TGF-β may be critical for FBM-MSCs mediated immunosuppressive function.

Depression is a common psychiatric disorder associated with chronic stress. Insulin-like growth factor 2 (IGF2) is a growth factor that serves important roles in the brain during development and at adulthood. Here, the role of IGF2 expression in the hippocampus was investigated in a rat model of depression.Read More

A chronic restraint stress (CRS) model of depression was established in rats, exhibiting depression-like behavior as assessed with the sucrose preference test (SPT) and forced swimming test (FST), and with evaluation of the corticosterone levels. Hippocampal IGF2 levels were significantly lower in rats suffering CRS than in controls, as were levels of pERK1/2 and GluR1. Lentivirus-mediated hippocampal IGF2 overexpression alleviated depressive behavior in restrained rats, elevated the levels of pERK1/2 and GluR1 proteins, but it did not affect the expression of pGSK3β, GluR2, NMDAR1, and NMDAR2A. These results suggest the chronic restraint stress induces depressive behavior, which may be mediated by ERK-dependent IGF2 signaling, pointing to an antidepressant role for this molecular pathway.

Increasing evidence shows that exposure to an enriched environment (EE) after cerebral ischemia/reperfusion injury has neuroprotective benefits in animal models, including enhancing functional recovery after ischemic stroke. However, the mechanism underlying this effect remains unclear. To clarify this critical issue, the current study investigated the effects of EE on the improvement of damaged neural function and the induction of angiogenesis.Read More

Adult rats were subjected to ischemia induced by middle cerebral artery occlusion followed by reperfusion. Neurological status scores were used to evaluate neural function on postoperative days 2, 7, and 14. A beam-walking task was used to test the recovery of motor behavior on postoperative days 2, 5, 10, and 15. We also used a Morris water maze task to examine whether EE protected learning and memory performance. The specific marker of angiogenesis of CD31 was examined by western blot. Angiogenesis around the peri-infarction region was assayed by laser scanning confocal microscopy (LSCM) after 14days of EE exposure starting 24h after ischemia. Neurological status scores of animals in the EE group were significantly higher than those in the standard housing condition (SC) control group from the seventh day after ischemic. EE accelerated the recovery of motor coordination and integration and also improved learning and memory performance after cerebral ischemia. Furthermore, EE increased CD31 levels and promoted angiogenesis of cortex in the peri-infarction region compared to the SC group. Neural function outcomes are positively correlated with post-ischemia angiogenesis. These findings suggest that EE plays an important role in the recovery of damaged neural function via regulation of angiogenesis after ischemia.

Anti-MHC Class I alloantibodies have been implicated in the processes of acute and chronic rejection. These antibodies (Ab) bind to endothelial cells (EC) and transduce signals leading to the activation of cell survival and proliferation pathways, including Src, FAK and mTOR, as well as downstream targets ERK, S6 kinase (S6K) and S6 ribosomal protein (S6RP). We tested the hypothesis that phosphorylation of S6K, S6RP and ERK in capillary endothelium may serve as an adjunct diagnostic tool for antibody-mediated rejection (AMR) in heart allografts.Read More


Diagnosis of AMR was based on histology or immunoperoxidase staining of paraffin-embedded tissue, consistent with 2013 ISHLT criteria. Diagnosis of acute cellular rejection (ACR) was based on ISHLT criteria. Endomyocardial biopsies from 67 heart transplant recipients diagnosed with acute rejection [33 with pAMR, 18 with ACR (15 with Grade 1R, 3 with Grade ≥2R), 16 with pAMR and ACR (13 with 1R and 3 with ≥2R)] and 40 age- and gender-matched recipients without rejection were tested for the presence of phosphorylated forms of ERK, S6RP and S6K by immunohistochemistry.
Immunostaining of endomyocardial biopsies with evidence of pAMR showed a significant increase in expression of p-S6K and p-S6RP in capillary EC compared with controls. A weaker association was observed between pAMR and p-ERK.
Biopsies diagnosed with pAMR often showed phosphorylation of S6K and S6RP, indicating that staining for p-S6K and p-S6RP is useful for the diagnosis of AMR. Our findings support a role for antibody-mediated HLA signaling in the process of graft injury.

To evaluate the reliability of a new scale, the Triple Spasticity Scale (TSS), for assessing spasticity in stroke, through measurement of affected elbow flexors and ankle plantar flexors of hemiplegic patients with stroke, and to compare the new scale with commonly used scales.
Cross-sectional study.
Inpatients at a rehabilitation hospital.Read More


Seventy-one inpatients with hemiplegic stroke.
TSS, Modified Ashworth Scale (MAS) and Modified Tardieu Scale (MTS).
Test-retest reliability for TSS total score was good (intraclass correlation coefficient (ICC) = 0.905~0.918). Inter- rater reliability for TSS total score was also good (ICC =  0.778~0.885). Spearman's correlation coefficient demonstrated significant correlation between the TSS and MAS, in both elbow flexors and plantar flexors (r = 0.840~0.946, p = 0.000), and between the TSS and MTS, in both elbow flexors and plantar flexors (r = 0.715~0.795, p = 0.000). There were small, but significant, correlations between the scores for increased resistance and dynamic muscle length in these 2 muscles (r = 0.307~0.564, p = 0.000~0.009).
The TSS has good test-retest reliability and inter-rater reliability in measurement of muscle tone. This new scale provides an alternative for measuring spasticity, which avoids some of the shortcomings of previous scales.

Direct detection of (13)C can be advantageous when studying uniformly enriched proteins, in particular for paramagnetic proteins or when hydrogen exchange with solvent is fast. A scheme recently introduced for long-observation-window band-selective homonuclear decoupling in solid state NMR, LOW-BASHD (Struppe et al. in J Magn Reson 236:89-94, 2013) is shown to be effective for (13)C(α) decoupling during direct (13)C' observation in solution NMR experiments too.Read More

For this purpose, adjustment of the decoupling pulse parameters and delays is demonstrated to be important for increasing spectral resolution, to reduce three-spin effects, and to decrease the intensity of decoupling side-bands. LOW-BASHD then yields (13)C' line widths comparable to those obtained with the popular IPAP method, while enhancing sensitivity by ca 35 %. As a practical application of LOW-BASHD decoupling, requiring quantitative intensity measurement over a wide dynamic range, the impact of lipid binding on the (13)C'-detected NCO spectrum of the intrinsically disordered protein α-synuclein is compared with that on the (1)H-detected (1)H-(15)N HSQC spectrum. Results confirm that synuclein's "dark state" behavior is not caused by paramagnetic relaxation or rapid hydrogen exchange.

Dopaminergic (DA) neuron-like cells obtained through direct reprogramming of primary human fibroblasts offer exciting opportunities for treatment of Parkinson's disease. A significant obstacle is the low efficiency of conversion during the reprogramming process. Here, we demonstrate that the suppression of p53 significantly enhances the efficiency of transcription factor-mediated conversion of human fibroblasts into functional dopaminergic neurons.Read More

In particular, blocking p53 activity using a dominant-negative p53 (p53-DN) in IMR90 cells increases the conversion efficiency by 5-20 fold. The induced DA neuron-like cells exhibit dopamine neuron-specific gene expression, significant dopamine uptake and production capacities, and enables symptomatic relief in a rat Parkinson's disease model. Taken together, our findings suggest that p53 is a critical barrier in direct reprogramming of fibroblast into dopaminergic neurons.

Dummy molecularly imprinted polymers (DMIPs) towards bisphenols (BPs) were prepared employing 1,1,1-tris(4-hydroxyphenyl)ethane (THPE) and phenolphthalein (PP) as dummy templates. The selectivity of the resulting DMIPs was evaluated by high-performance liquid chromatography (HPLC). Both PP-DMIP and THPE-DMIP showed excellent class selectivity towards bisphenols.Read More

THPE-DMIP prepared using the template molecule with three hydroxyphenyl functionalities achieved higher imprinting factors (IF) for the bisphenols over a range of 7.9-19.8. An efficient approach based on dummy molecularly imprinted solid phase extraction (DMISPE) coupled with HPLC-DAD was developed for selective extraction of eight bisphenols in sediment, milk and human urine samples using THPE-DMIP as sorbents. The method showed good recoveries (82-102%) and precision (RSD 0.2-4%, n=3) for these samples spiked at two concentration levels (25 and 250ngg(-1) or ngmL(-1)). The detection limits ranged between 0.6 and 1.1ngg(-1) or ngmL(-1). Efficient removal of sample matrix and interferences was also achieved for these samples after DMISPE process. The results demonstrated great potential of the optimized methods for sample preparation in the routine analysis of trace BPs in complex samples.

The addition of an appropriate adjuvant that activates the innate immunity is essential to subsequent development of the adaptive immunity specific to the vaccine antigens. Thus, any innovation capable of improving the immune responses may lead to a more efficacious vaccine. We recently identified a novel immune modulator using a naturally occurring seed peptide called lunasin.Read More

Lunasin was originally isolated from soybeans, and it is a small peptide containing 43 amino acids. Our studies revealed stimulatory effects of lunasin on innate immune cells by regulating expression of a number of genes that are important for immune responses. The objective was to define the effectiveness of lunasin as an adjuvant that enhances immune responses. The immune modulating functions of lunasin were characterized in dendritic cells (DCs) from human peripheral blood mononuclear cells (PBMCs). Lunasin-treated conventional DCs (cDCs) not only expressed elevated levels of co-stimulatory molecules (CD86, CD40) but also exhibited up-regulation of cytokines (IL1B, IL6) and chemokines (CCL3, CCL4). Lunasin-treated cDCs induced higher proliferation of allogeneic CD4+ T cells when comparing with medium control treatment in the mixed leukocyte reaction (MLR). Immunization of mice with ovalbumin (OVA) and lunasin inhibited the growth of OVA-expressing A20 B-lymphomas, which was correlated with OVA-specific CD8+ T cells. In addition, lunasin was an effective adjuvant for immunization with OVA, which together improved animal survival against lethal challenge with influenza virus expressing the MHC class I OVA peptide SIINFEKL (PR8-OTI). These results suggest that lunasin may function as a vaccine adjuvant by promoting DC maturation, which in turn enhances the development of protective immune responses to the vaccine antigens.

Atmospheric polychlorinated naphthalenes (PCNs) ranging from mono-CNs to octa-CNs were detected using isotope-dilution gas chromatography coupled with triple quadrupole mass spectrometry (GC-MS/MS). The developed instrumental method was successfully applied to the determination of PCNs in technical products. It was observed that there were significant differences in concentrations, homologue profiles, chlorinated contents and total toxic equivalents (∑TEQs) of PCNs for four Halowax products.Read More

Subsequently, the validation of the analytical method was evaluated for the determination of PCNs in air samples in terms of method detection limit (MDL), recovery and matrix effect. The results demonstrated that this method could provide satisfactory sensitivity and adequate selectivity with lower cost. It was conducted to comprehensively evaluate the levels, composition patterns, ∑TEQs, and daily intake exposure of PCNs in indoor and outdoor air samples. Concentrations and ∑TEQs of PCNs in air samples ranged 47.7-832.7 pg m(-3) and 1.31-5.99 fg m(-3), respectively, and the predominant homologues were di- and tri-CNs in the gas phase. The results indicated that this analytical method was useful for the accurate and specific evaluation of dioxin-like toxicity and human exposure levels of PCNs in the atmosphere.

This study evaluated preferences for shared decision making with respect to mental health treatment in a sample of veterans who were diagnosed as having serious mental illness.
Participants were 239 outpatients receiving care from the Department of Veterans Affairs who completed self-report questionnaires assessing demographic factors, shared decision-making preferences, psychiatric symptom severity, and the therapeutic relationship with their second-generation antipsychotic prescribers (N=21). Preferences were assessed in regard to three components of decision making: knowledge about mental illness, options about mental health treatment, and decisions about mental health care.Read More


Most participants (85%) indicated that they preferred to be offered options and to be asked their opinions about mental health treatment. More variability was noted in preferences for obtaining knowledge and making final treatment decisions; 61% preferred to rely on their providers' knowledge and 64% preferred their provider to make treatment final decisions. Greater preferences for participation in shared decision making were found among African American clients, those currently working for pay, those with college or higher education, those with other than a schizophrenia spectrum diagnosis, and those who reported a poorer therapeutic relationship with their prescribers.
The degree to which veterans with serious mental illness desired to participate in their mental health care differed in terms of the aspect of care and across demographic and clinical factors. A thorough assessment of shared decision-making preferences is an important component of recovery-oriented, client-centered care.

This study investigated the expression of Sonic Hedgehog (Shh) protein in gastric cancer, and correlated it with clinicopathological parameters. The prognostic significance of Shh protein was analyzed.
Shh protein expression was evaluated in 113 cases of gastric cancer and 60 cases of normal gastric mucosa.Read More

The immunoreactivity was scored semi quantitatively as: 0 = absent; 1 = weak; 2 = moderate; and 3 = strong. All cases were further classified into two groups, namely non-overexpression group with score 0 or 1, and overexpression group with score 2 or 3. The overexpression of Shh protein was correlated with clinicopathological parameters. Survival analysis was then performed to determine the Shh protein prognostic significance in gastric cancer.
In immunohistochemistry study, nineteen (31.7%) normal gastric mucosa revealed Shh protein overexpression, while eighty-one (71.7%) gastric cancer revealed overexpression. The expression of Shh protein were significantly higher in gastric cancer tissues than in normal gastric mucosa (P < 0.001), which was statistically correlated with age (P = 0.006), tumor differentiation (P < 0.001), depth of invasion (P = 0.042), pathologic staging (P = 0.017), and nodal metastasis (P = 0.019). We found no significant difference in both overall and disease free survival rates between Shh overexpression and non-expression groups P = 0.168 and 0.071). However, Shh overexpression emerged as a significant independent prognostic factor in multivariate Cox regression analysis (hazard ratio 1.187, P = 0.041).
Shh protein expression is upregulated and is statistically correlated with age, tumor differentiation, depth of invasion, pathologic staging, and nodal metastasis. The Shh protein overexpression is a significant independent prognostic factor in multivariate Cox regression analysis in gastric cancer.

2014Sep
Biomed Mater Eng
Biomed Mater Eng 2014 ;24(6):3207-14

Surface registration is widely used in image-guided neurosurgery to achieve spatial registration between the patient space and the image space. Coarse registration, followed by fine registration, is an important premise to ensure the robustness and efficiency of surface registration. In this paper, a coarse registration algorithm based on the principal axes is proposed to achieve this goal.Read More

The extraction of the principal axes relies on the approximated surface with an adaptive Gaussian kernel, the width of which is consistent with neighborhood relation so that it is applicable for various scanning data. Determining the corresponding centers of translation is another problem for aligning different scanning data, which is solved through heuristics. Six pairs of points on two surfaces with the farthest projections on the principal axes were regarded as the candidates of translation centers, and then through tentative alignments of local regions around them, a pair of candidates with the minimum registration error was selected as the optimal translation centers. Automatic registration of two scans of a head phantom is presented in this paper. Experimental results confirmed the robustness of the algorithm and its feasibility in clinical applications.

The high performance liquid chromatography (HPLC) enantioseparation of four β-blocking agents metoprolol, bisoprolol, propranolol and atenolol was performed on amylose tris-(3,5-dimethylphenylcarbamate) chiral stationary phase using n-hexane-ethanol-diethylamine (DEA) as the mobile phase and related chiral recognition mechanisms were discussed. Enantiomeric separation of the four β-blockers was a result of more than one type of interaction between solutes and CSP. Besides hydrogen bonding, there was another type interaction that was independent of solvent polarity and responsible for enantiomeric selectivity, such as - interactions.Read More

Both the groups close to the chiral centers and the substituent groups on the phenyl rings, which were far away from the chiral centers, could contribute to the good separation. The separations of the four β-blocker enantiomers were all enthalpy driven process. In the range of 293-308K (20-35 ℃), as the temperature increased, the retention as well as the resolution decreased. The molecular size rather than concentration of the alcohol modifiers affected the resolution and retention.

Beauveria bassiana, a filamentous entomopathogen, has five distinct superoxide dismutases (SODs), including cytosolic and mitochondrial MnSODs (Sod2/3) which have proved contributing primarily to intracelluar SOD activity and additively to antioxidation and virulence. Here we characterized cytosolic Cu/ZnSOD (Sod1), mitochondrial FeSOD (Sod4) and cell wall-anchored Cu/ZnSOD (Sod5). The latter two are unexplored despite existence in many filamentous fungi, and their subcellular localization was well confirmed with specifically stained cells expressing Sod4::eGFP or Sod5::eGFP fusion.Read More

Total SOD activity decreased by ∼15% in Δsod1 but increased by 11-20% in three sod4 knockdown mutants (Δsod4 was lethal) when co-cultivated with menadone and H2O2. Surprisingly, total catalase activity decreased much more in the sod4 mutants (69-75%) than in Δsod1 (27-33%) under normal and oxidative conditions. However, Δsod5 showed little change in either SOD or catalase activity. Transcript levels of SOD partners and five catalases also changed more dramatically in the sod4 mutants than in Δsod1 and Δsod5. As a consequence of global effect, intracellular ROS levels induced by both oxidants were higher in Δsod1 than in the sod4 mutants and Δsod5. All the mutants were differentially more sensitive to the two oxidants and UV-A/UV-B irradiations and less virulent to Galleria mellonella larvae but not responsive to high osmolarity, cell wall stress and high temperature. Taken together with previously characterized Sod2 and Sod3, our results provide full insight into the SOD family, unveiling the interactions of each SOD with other partners and catalases in the antioxidant reaction associated with the fungal biocontrol potential.

The 3D Gerchberg-Saxton (GS) algorithm can be used to compute a computer-generated hologram (CGH) to produce a 3D holographic display. But, using the 3D GS method, there exists a serious distortion in reconstructions of binary input images. We have eliminated the distortion and improved the image quality of the reconstructions by a maximum of 486%, using a symmetrical 3D GS algorithm that is developed based on a traditional 3D GS algorithm.Read More

In addition, the hologram computation speed has been accelerated by 9.28 times, which is significant for real-time holographic displays.

This study was aimed to investigate the change of cell phenotype and the expression of hematopoiesis associated cytokines in umbilical cord mesenchymal stem cells (UC-MSC) in three-dimensional (3-D) system. MSC were isolated from umbilical cord, and then cultured in 2-D and 3-D system respectively. The phenotype of MSC was detected by flow cytometry; the angiogenic capability of MSC cultured in 2-D and 3-D syitem was assessed using in vitro capillary formation assay.Read More

The cytokine expression of MSC in two kinds of culture conditions was measured by real-time PCR. The results showed that MSC were successfully isolated from umbilical cord. Flow cytometry showed that the percentage of CD31, CD133 and CD271 expressed in endothelial cells, endothelial progenitor cells and primitive mesenchymal stem cells increased significantly in 3-D culture conditions, as compared to 2-D system. Capillary formation assay showed that the angiogenic capability of UC-MSC was greatly enhanced. Quantitative PCR showed that the expression of β-actin was upregulated in 3-D system. The expression of some cytokines associated with hematopoiesis, such as G-CSF, LIF, SCF, IL-1α, IL-1β, IL-3, IL-7 and IL-11, increased, especially for LIF, IL-3, IL-7. The expression of IL-10 associated with immune regulation also increased. The expression of SDF-1, IL-6 slightly decreased, but without significant difference. It is concluded that expression of CD31, CD133 and CD271 increases in 3-D system, the angiogenic capability of UC-MSC enhances and the expression of hematopoiesis-associated cytokines in UC-MSC increases in 3-D system.

It was reported that BRAF mutation correlates with radioactive iodine refractory papillary thyroid carcinoma (PTC) in local recurrence, whereas its relationship with I uptake status in distant metastatic PTC remains uncertain. This prospective study tried to explore the association between I uptake in distant metastases (DM) of PTC and BRAF mutation status in their primary tumor.
Seventy-three patients with DM were divided into BRAF mutation group (n = 19) and wild-type BRAF group (n = 54) according to the BRAF mutation status.Read More

After posttherapy I whole-body scan was performed, the relation between I uptake in DM, BRAF mutation status, and clinicopathological characteristics of 2 groups were compared.
The mean age of mutation group was older than that of the wild-type group (P < 0.05). In the mutation group, 16 patients (84.2%, 16 of 19) were found to be with non-iodine-avid DM, whereas in wild-type group, only 5.6% (3 of 54) were with non-iodine-avid DM. The sensitivity and specificity of using BRAF mutation for the identification of non-iodine-avid DM were 84.2% and 94.4%, respectively.
BRAF mutation in primary tumor might be a promising molecular marker to predict the status of I uptake in distal metastases.

Limb-girdle muscular dystrophy type 2B,a type of dysferlinopathy, is caused by mutations in the dysferlin gene (DYSE). It is characterized by predominant weakness and atrophy of muscles of the pelvic and shoulder girdles, massive elevation of serum CK concentration, slow progression, and onset usually within the second or third decade of life. We present a Chinese patient whose disease onset was at the age of 50 years with persistent elevation of transaminases for 3 years before weakness appeared.Read More

She had been considered as having liver disease for a long time and then polymyositis. Finally, biceps brachii biopsy revealed dystrophic morphology and depletion of dysferlin in immunohistochemistry. This case should remind readers that late-age onset of dysferlinopathy can be misdiagnosed as liver disease or polymyositis.

A gigantic Co14-containing 36-niobate, Na12K8[Co14(OH)16(H2O)8Nb36O106]⋅71H2O (1), has been prepared by the hydrothermal method and structurally characterized. Polyanion [Co14(OH)16(H2O)8Nb36O106](20-) (1 a) comprises a central Co7 core, surrounded by another seven isolated Co(2+) ions and six Lindqvist-type (Nb6O19) hexaniobate fragments. This is the first example of a high-nuclear cobalt-cluster-containing polyoxoniobate.Read More

The photocatalytic H2 evolution activity of Pt-loaded 1 was observed in methanol solution under irradiation using a 300 W Xe lamp.

AIDS remains incurable due to the permanent integration of HIV-1 into the host genome, imparting risk of viral reactivation even after antiretroviral therapy. New strategies are needed to ablate the viral genome from latently infected cells, because current methods are too inefficient and prone to adverse off-target effects. To eliminate the integrated HIV-1 genome, we used the Cas9/guide RNA (gRNA) system, in single and multiplex configurations.Read More

We identified highly specific targets within the HIV-1 LTR U3 region that were efficiently edited by Cas9/gRNA, inactivating viral gene expression and replication in latently infected microglial, promonocytic, and T cells. Cas9/gRNAs caused neither genotoxicity nor off-target editing to the host cells, and completely excised a 9,709-bp fragment of integrated proviral DNA that spanned from its 5' to 3' LTRs. Furthermore, the presence of multiplex gRNAs within Cas9-expressing cells prevented HIV-1 infection. Our results suggest that Cas9/gRNA can be engineered to provide a specific, efficacious prophylactic and therapeutic approach against AIDS.

A new photoinduced three-component reaction between a cyanoarene, an alkene and an N-protected pyrrole has been developed. This reaction extended the scope of the photo-NOCAS reaction by introducing pyrrole as a neutral carbon-centered nucleophile. The cyanoarenes used include tetracyanobenzene (TCB), 2,3,5,6-tetrafluoro-1,4-dicyanobenzene (TFDCB) and 1,4-dicyanobenzene (DCB).Read More

N-Methyl, N-phenyl and N-Boc pyrroles are suitable nucleophiles in the reaction. Taking advantage of the strong electron acceptor ability of the singlet excited TCB, a wide range of alkenes, including the highly electron deficient 4-fluoro-, 4-chloro-, 2,3,4,5,6-pentafluorostyrenes and N-methylmaleimide take part in this reaction, leading to the simultaneous 1,2-diarylation of the alkene and the regioselective 2-alkylation of the pyrrole ring via sequential formation of two new C-C bonds between the three reactants.

2014Aug
Evid Based Complement Alternat Med
Evid Based Complement Alternat Med 2014 7;2014:483294. Epub 2014 Jul 7.

Oxidative stress participates in the pathological process of various diseases. Acupuncture is a component of the health care system in China that can be traced back for at least 3000 years. Recently, increased evidences indicate that acupuncture stimulation could reduce oxidative damage in organisms under pathological state, but the exact mechanism remains unclear.Read More

This review focuses on the emerging links between acupuncture and redox modulation in various disorders, such as vascular dementia, Parkinson's disease, and hypertension, ranging from redox system, antioxidant system, anti-inflammatory system, and nervous system to signaling pathway. Although the molecular and cellular pathways studies of acupuncture effect on oxidative stress are preliminary, they represent an important step forward in the research of acupuncture antioxidative effect.

Middle East respiratory syndrome coronavirus (MERS-CoV) currently spreads in humans and causes ∼ 36% fatality in infected patients. Believed to have originated from bats, MERS-CoV is genetically related to bat coronaviruses HKU4 and HKU5. To understand how bat coronaviruses transmit to humans, we investigated the receptor usage and cell entry activity of the virus-surface spike proteins of HKU4 and HKU5.Read More

We found that dipeptidyl peptidase 4 (DPP4), the receptor for MERS-CoV, is also the receptor for HKU4, but not HKU5. Despite sharing a common receptor, MERS-CoV and HKU4 spikes demonstrated functional differences. First, whereas MERS-CoV prefers human DPP4 over bat DPP4 as its receptor, HKU4 shows the opposite trend. Second, in the absence of exogenous proteases, both MERS-CoV and HKU4 spikes mediate pseudovirus entry into bat cells, whereas only MERS-CoV spike, but not HKU4 spike, mediates pseudovirus entry into human cells. Thus, MERS-CoV, but not HKU4, has adapted to use human DPP4 and human cellular proteases for efficient human cell entry, contributing to the enhanced pathogenesis of MERS-CoV in humans. These results establish DPP4 as a functional receptor for HKU4 and host cellular proteases as a host range determinant for HKU4. They also suggest that DPP4-recognizing bat coronaviruses threaten human health because of their spikes' capability to adapt to human cells for cross-species transmissions.

To evaluate the outcomes of nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT).
Between September 2007 and August 2012, 190 newly diagnosed NPC patients were treated with HT. Thirty-one patients were treated with radiation therapy as single modality, 129 with additional cisplatin-based chemotherapy with or without anti-EGFR monoclonal antibody therapy, and 30 with concurrent anti-EGFR monoclonal antibody therapy.Read More


Acute radiation related side effects were mainly grade 1 or 2. Grade 3 and greater toxicities were rarely noted. The median followup was 32 (3-38) months. The local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were 96.1%, 98.2%, 92.0%, and 86.3%, respectively, at 3 years. Cox multivariate regression analysis showed that age and T stage were independent predictors for 3-year OS.
Helical tomotherapy for NPC patients achieved excellent 3-year locoregional control, distant metastasis-free survival, and overall survival, with relatively minor acute and late toxicities. Age and T stage were the main prognosis factors.

Saponins of several herbs are known to induce apoptosis in many cancer cells. The present study aimed to investigate the growth inhibitory effect of Paris saponin VII (PS VII), a kind of steroidal saponins from Chonglou (Rhizoma Paridis Chonglou), on the human cervical cancer cell line Hela and the relative molecular mechanisms.
Hela cells were exposed to different concentrations of PS VII (1 to 100 μM).Read More

Inhibition of cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 5-ethynyl-2'-deoxyuridine (EdU) assays. The amount of apoptotic cells was evaluated by flow cytometric analysis. And the protein level of cleaved caspase-3, cleaved caspase-9, Bax, and Bcl-2 was evaluated by Western blot.
The half maximal inhibitory concentration (IC50) value of PS VII for the growth inhibition of Hela cells was 2.62 ± 0.11 μM. PS VII increased the expression of caspase-3, caspase-9, and Bax while decreased that of Bcl-2, suggesting that PS VII may induce apoptosis through intrinsic apoptotic ways.
These data indicate that PS VII has the potential for the treatment of cervical cancer.

Previous studies had shown that elevated admission plasma glucose (APG) could increase mortality rate and serious complications of acute myocardial infarction (AMI), but whether fasting plasma glucose (FPG) had the same role remains controversial. In this retrospective study, 253 cases of AMI patients were divided into diabetic (n = 87) and nondiabetic group (n = 166). Our results showed that: compared with the nondiabetic patients, diabetic patients had higher APG, FPG, higher plasma triglyceride, higher rates of painless AMI (P < 0.Read More

01), non-ST-segment elevation myocardial infarction (NSTEMI), and reinfraction (P < 0.05). They also had lower high density lipoprotein cholesterol and rate of malignant arrhythmia, but in-hospital mortality rate did not differ significantly (P > 0.05). While nondiabetic patients were subgrouped in terms of APG and FPG (cut points were 11.1 mmol/L and 7.0 mmol/L, resp.), the mortality rate had significant difference (P < 0.01), whereas glucose level lost significance in diabetic group. Multivariate logistic regression analysis showed that FPG (OR: 2.014; 95% confidence interval: 1.296-3.131; p < 0.01) but not APG was independent predictor of in-hospital mortality for nondiabetic patients. These results indicate that FPG can be an independent predictor for mortality in nondiabetic female patients with AMI.

2014Aug
Soc Work Health Care
Soc Work Health Care 2014 ;53(7):679-92

China faces an overwhelming and urgent need for long-term care (LTC). We explored long-term care insurance (LTCI) plans in China and the factors associated with each plan's contribution rate. A cross-sectional survey of 814 residents (18-59 years) was conducted to assess the expectations of elderly care, public and private LTCI features.Read More

Public LTCI may be more popular whether in terms of participation or contribution. The factors associated with public LTCI contribution rate were healthcare costs, household income, and number of daughters; for private LTCI, the factors were the proportion of living expenditures, worry about future care problems, and healthcare costs. Policymakers should develop public LTCI as a solid foundation and improve private LTCI as a substitute to meet the urgent LTC needs in China.

A Sister Mary Joseph nodule represents an umbilical metastasis, which is more commonly caused by a primary malignancy in gastrointestinal tract or from reproductive system. We report Sister Mary Joseph nodules caused by neuroendocrine tumor and revealed on Tc HYNIC-TOC scintigraphy.Read More

To distinguish the impact of mental illness stigma from that of other negative caregiving experiences, this study examined the unique relationships between stigma and caregiver/family functioning. Adult relatives (n = 437) of individuals with mental illness completed questionnaires regarding caregiving experiences, distress, empowerment, and family functioning, as part of a larger study. Regression analyses examined the relationship between stigma and caregiver/family variables, while controlling for other negative caregiving experiences.Read More

Stigma was uniquely associated with caregiver distress, empowerment, and family functioning. Mental illness stigma is a potent source of distress for families and an important target of family services.

This paper presents an effective utilization of slag from acid leaching of coal-waste with a novel approach, namely low-temperature co-melting method, for preparation of sodium silicate (Na2O x nSiO2) using slag from acid leaching of coal-waste as feedstock. It is very interesting that the co-melting reaction temperature of the mixture of Na2CO3 and the feedstock (50-100 microm) was as low as 850 degrees C, which was significantly lower than the temperature used in traditional sodium silicate production (1400 degrees C). The optimum SiO2/Na2O ratio was identified as 7:3 according to the results of thermogravimetry-differential scanning calorimetry (TGA-DSC), ICP-AES, and X-ray diffraction (XRD) analyses.Read More

In this condition, the main product was sodium disilicate (Na2O x 2SiO2), with water solubility of 85.0%. More importantly, the impurities such as aluminum in the feedstock, which had adverse effect on subsequent treatment, were concentrated almost completely in the filter residue as insoluble sodium alumunosilicates, i.e., Na(Si2Al)O6 x H2O. The lower co-melting temperature of this process demonstrates a significant energy-saving opportunity and thus a promising approach for highly effective utilization of coal-waste. Implications: Recently, alumina extraction from coal-waste has been extensively investigated and industrial applied in China. However, the slag-containing silica generated from the acid leaching process of coal-waste led to a secondary pollution, which hindered large-scale production. The proposed low-temperature co-melting method for preparation of sodium silicate (Na2O x nSiO2) using slag from acid leaching of coal-waste as feedstock indicated that it is an efficient approach for the recovery of silica from the acid-leached slag of coal-waste with minimal environmental impact.

2014Aug

To study the types of matrix metalloproteinases (MMPs) involved in dentin bonding interface degradation.
Dentin slices were prepared and treated with two adhesive systems (Single Bond 2 or Clearfil S3 Bond). The dentin surface was bonded with composite resin.Read More

All specimens were immersed in sterile artificial saliva for 0 or 6 months, and their micro-shear bond strength (muSBS) were measured. The fracture modes were observed through field emission scanning electron microscope (FE-SEM). Dentin slices with 4 mm x 3 mm x 1 mm dimensions were prepared. The slices were divided into three groups according to the treatment modes (negative control, Single Bond 2, and Clearfil S3 Bond). All specimens were stored in sterile artificial saliva for 0 or 6 months. The concentrations of MMP-1, -2, -3, -8, and -9 of each group were detected through fluorescent microsphere immunoassay.
The muSBS of both adhesive systems significantly decreased after storage aging. Significant differences in failure modes within the four groups tested in this study were observed. Compared with the negative control, the concentrations of MMP-1 and MMP-3 in different adhesive groups showed no significant difference after storage aging. However, the concentrations of MMP-2, -8, and -9 in Single Bond 2 group and the concentrations of MMP-8 and -9 in Clearfil S3 Bond group significantly decreased after 6 months of storage aging.
Significant degradation occur in the dentin bonding interface of both adhesive groups under 6 months aging challenge. The concentrations ofdentinal MMP-2, -8, and -9 significantly decrease after treatment with adhesives and aging, indicating that these MMPs have an important function in dentin bonding interface degradation.

To compare therapeutic effects between unilateral decompression technique only and open decompression technique with fusion and internal fixation for the treatment of lumbar spinal stenosis.
From March 2008 to February 2011, 82 patients with lumbar spinal stenosis were treated with operations, and divided into two groups. There were 13 males and 19 females in group A, with a mean age of (56.Read More

31±4.31) years old. The patients in group A were treated with unilateral decompression via fenestration technique only, including 23 patients obtaining single level decompression and 9 patients obtaining two levels decompression. In group B, there were 18 males and 32 females, with a mean age of (57.53±4.28) years old. The patients in group B were treated with open decompressive technique with fusion and internal fixation, including 38 patients obtaining single level decompression and 12 patients obtaining two levels decompression. The VAS of back pain and leg pain, ODI were recorded before and after surgery to evaluate low back pain,leg pain and walking tolerance.
All the patients were followed up, and the duration ranged from 10.9 to 43.4 months,with a mean of 32.8 months. There were no differences in age, stenosis level, VAS of back and leg pain and ODI before surgery between two groups. Compared with the corresponding ones in group B, the operation time, blood loss, hospitalization time,recovery time of routine daily life and finacial expenditure of patients were all shorter or less in group A. There was no statistically difference in complications between two groups.
"Unilateral decompression via fenestration technique" is a less invasive and more effective decompressive technique for degenerative spinal stenosis without posterior elements damage. It has advantages in operation time, blood loss, hospitalization time, recovery to daily life and financial expenditure. When controlling the operative indications strictly, the technique could be an important procedure for surgical treatment of degenerative spinal stenosis, especially in the elderly population.

To compare therapeutic effects between unilateral decompression technique only and open decompression technique with fusion and internal fixation for the treatment of lumbar spinal stenosis.
From March 2008 to February 2011, 82 patients with lumbar spinal stenosis were treated with operations, and divided into two groups. There were 13 males and 19 females in group A, with a mean age of (56.Read More

31±4.31) years old. The patients in group A were treated with unilateral decompression via fenestration technique only, including 23 patients obtaining single level decompression and 9 patients obtaining two levels decompression. In group B, there were 18 males and 32 females, with a mean age of (57.53±4.28) years old. The patients in group B were treated with open decompressive technique with fusion and internal fixation, including 38 patients obtaining single level decompression and 12 patients obtaining two levels decompression. The VAS of back pain and leg pain, ODI were recorded before and after surgery to evaluate low back pain,leg pain and walking tolerance.
All the patients were followed up, and the duration ranged from 10.9 to 43.4 months,with a mean of 32.8 months. There were no differences in age, stenosis level, VAS of back and leg pain and ODI before surgery between two groups. Compared with the corresponding ones in group B, the operation time, blood loss, hospitalization time,recovery time of routine daily life and finacial expenditure of patients were all shorter or less in group A. There was no statistically difference in complications between two groups.
"Unilateral decompression via fenestration technique" is a less invasive and more effective decompressive technique for degenerative spinal stenosis without posterior elements damage. It has advantages in operation time, blood loss, hospitalization time, recovery to daily life and financial expenditure. When controlling the operative indications strictly, the technique could be an important procedure for surgical treatment of degenerative spinal stenosis, especially in the elderly population.

The debate on the effects and outcome of olfactory ensheathing cell (OEC) transplantation for the treatment of spinal cord injury (SCI) has remained unresolved for nearly 20 years. This study aimed to evaluate the safety and efficacy of OEC transplantation in chronic SCI patients.
Electronic databases, including PubMed, the Cochrane Library, EMBASE, and MEDLINE, were searched to identify clinical therapeutic trials studying the use of OEC transplantation for SCI in humans.Read More

Each trial was analyzed in accordance with the criteria of the Cochrane Handbook 5.1.0 and MOOSE. Data were analyzed with Review Manager 5.2 and Meta-Analyst Beta 3.13 software.
Eleven articles concerning 10 studies of 1,193 patients with chronic SCI treated with OEC transplantation were selected for review. All the articles had low methodological quality. Studies reported their outcomes using the American Spinal Injury Association (ASIA) Impairment Scale; the AISA motor, light touch, pinprick score; the Functional Independence Measure and (or) other measure methods. According to the available relevant data, the incidences of total adverse events and mortality were 7.68 % (n = 742) and 0.35 % (n = 566), respectively. The most frequently reported adverse events were fever, mild anemia, and syringomyelia; however, the statistical adverse events occurring in different studies were cerebrospinal fluid leakage (7.00 %, n = 586, 2 trials), sensory deterioration (0.70 %, n = 573, 2 trials), and both motor and sensory deterioration (0.68 %, n = 586, 2 trials).
Given the results from our study, we conclude that OEC transplantation appears to be safe, although the evidence for efficacy is modest and requires the support of prospective, randomized trials in larger cohorts of patients. Further randomized controlled trials utilizing strict therapy programs and implanted cell selections are needed to confirm these findings.

LPS-binding protein (LBP) and its ligand CD14 are located upstream of the signaling pathway for LPS-induced inflammation. Blocking LBP and CD14 binding might prevent LPS-induced inflammation. In previous studies, we obtained a peptide analog (MP12) for the LBP/CD14 binding site and showed that this peptide analog had anti-endotoxin activity.Read More

In this study, we used in vitro directed evolution for this peptide analog to improve its in vivo and in vitro anti-endotoxin activity.
We used error-prone PCR (ep-PCR) and induced mutations in the C-terminus of LBP and attached the PCR products to T7 phages to establish a mutant phage display library. The positive clones that competed with LBP for CD14 binding was obtained by screening. We used both in vivo and in vitro experiments to compare the anti-endotoxin activities of a polypeptide designated P1 contained in a positive clone and MP12.
11 positive clones were obtained from among target phages. Sequencing showed that 9 positive clones had a threonine (T) to methionine (M) mutation in amino acid 287 of LBP. Compared to polypeptide MP12, polypeptide P1 significantly inhibited LPS-induced TNF-α expression and NF-κB activity in U937 cells (P<0.05). Compared to MP12, P1 significantly improved arterial oxygen pressure, an oxygenation index, and lung pathology scores in LPS-induced ARDS rats (P<0.05).
By in vitro directed evolution of peptide analogs for the LBP/CD14 binding site, we established a new polypeptide (P1) with a threonine (T)-to-methionine (M) mutation in amino acid 287 of LBP. This polypeptide had high anti-endotoxin activity in vitro and in vivo, which suggested that amino acid 287 in the C-terminus of LBP may play an important role in LBP binding with CD14.

This paper investigates the feasibility of the resonant metalens for the imaging beyond the diffraction limit using a single sensor in the far-field. It is shown that the resonant metalens can be related to the super-resonance phenomenon. We demonstrate that the super-resonance supports the enhancement of the information capacity of an imaging system, which is responsible for the subwavelength imaging of the probed objects by using a single sensor in combination with a broadband illumination.Read More

Such imaging concept has its unique advantage of producing real-time data when an object is illuminated by broadband waves, without the harsh requirements such as near-field scanning, mechanical scanning, or antenna arrays. The proposed method is expected to find its applications in nanolithography, detection, sensing, and subwavelength imaging in the near future.

By means of field sampling and laboratory analysis, the content distribution characteristics of Cd, Cr, Cu, Ni, Pb and Zn in agricultural region soils of Huaihe basin in Anhui province were analyzed. Assessment of heavy metal pollutions was conducted using enrichment factor, geoaccumulation index and potential ecological risk index. The results showed that the average mass fraction of Cd and Cu was 0.Read More

113 5 and 22.09 mg x kg(-1) respectively in the study area soil, which were above the background values 0.097 and 20.4 mg x kg(-1) in Anhui Province. The average mass fraction of other four heavy metals did not exceed the average values of Anhui Province. The results of the evaluations from geoaccumulation index and ecological risk assessment discovered that Cd is the strongest pollution metal among six heavy metals in the study area soil. For some samples of the study soil, Cd was slight risk for the ecosystem. The ecosystem risks caused by the other five heavy metals were not obviously for the sampling points. The entire study area soils were mid integrated potential ecological risk.

Ischemic vascular diseases, including myocardial infarction (MI) and stroke, have been found to be associated with elevated expression of αvβ3-integrin, which provides a promising target for semi-quantitative monitoring of the disease. For the first time, we employed (68)Ga-S-2-(isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid-PEG3-E[c(RGDyK)]2 ((68)Ga-PRGD2) to evaluate the αvβ3-integrin-related repair in post-MI and post-stroke patients via positron emission tomography/computed tomography (PET/CT).
With Institutional Review Board approval, 23 MI patients (3 days-2 years post-MI) and 16 stroke patients (3 days-13 years post-stroke) were recruited.Read More

After giving informed consent, each patient underwent a cardiac or brain PET/CT scan 30 min after the intravenous injection of (68)Ga-PRGD2 in a dose of approximately 1.85 MBq (0.05 mCi) per kilogram body weight. Two stroke patients underwent repeat scans three months after the event.
Patchy (68)Ga-PRGD2 uptake occurred in or around the ischemic regions in 20/23 MI patients and punctate multifocal uptake occurred in 8/16 stroke patients. The peak standardized uptake values (pSUVs) in MI were 1.94 ± 0.48 (mean ± SD; range, 0.62-2.69), significantly higher than those in stroke (mean ± SD, 0.46 ± 0.29; range, 0.15-0.93; P < 0.001). Higher (68)Ga-PRGD2 uptake was observed in the patients 1-3 weeks after the initial onset of the MI/stroke event. The uptake levels were significantly correlated with the diameter of the diseases (r = 0.748, P = 0.001 for MI and r = 0.835, P = 0.003 for stroke). Smaller or older lesions displayed no uptake.
(68)Ga-PRGD2 uptake was observed around the ischemic region in both MI and stroke patients, which was correlated with the disease phase and severity. The different image patterns and uptake levels in MI and stroke patients warrant further investigations.

To evaluate the effects and safeness of combined hysterolaparoscopy on evaluation the causes of infertility.
This retrospective study was conducted at the Department of Gynecology (The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China) from January 2011 to April 2014. Patients aged 21-43 years with infertility were included in this study.Read More

The prevalence of different lesions was collected to analyze.
132 infertile patients were included, 71 (53.8%) women had primary infertility and the rest 61 (46.2%) had secondary infertility. Laparoscopic abnormalites were more common than hysteroscopy abnormalites both in primary infertility group and secondary infertility group. Pelvic inflammatory disease (59.09 %) and endometriosis (29.55%) were the most common abnormalities in two groups. The most common intrauterine pathology was uterine polyps and the most common uterine malformation was uterine septum in two groups. Out of 12 patients having malformation uterus, only one was double uterus and double cervical with double vagina. There was no major surgical or anesthetic complication in any of our patients, other than mild abdominal pain.
Hysterolaparoscopy is an effective and safe tool in comprehensive evaluation of infertility to diagnosis and treat the lesions of pelvic and uterus in the same time. Hysterolaparoscopy may be recommended as the first and final procedure for evaluation of female infertility.

To systematically investigate the aging effect of thermocycling, water storage and bacteria aggression on the stability of resin-dentin bonds.
Forty molars were sectioned perpendicularly to the axis of the teeth to expose the middle-coronal dentin surfaces. The dentin surfaces were then treated with Single Bond 2 and made a core build-up.Read More

According to random digits table, the bonding specimens were divided into four groups (n = 10) as follows: immediate control group, aging group with thermocycling for 5 000 times, aging group with artificial saliva storage for 6 months and aging group with bacteria aggression for 14 days. The specimens in each group were then subjected to microtensile bond strengths (µTBS) testing and nanoleakage evaluation respectively.
After aging treatments, the three aging groups showed significantly lower µTBS than the immediate control group [(44.24 ± 12.75) MPa, P < 0.05]. The immediate control group also showed the lowest value of nanoleakage. The µTBS of aging group with bacteria aggression [(25.53 ± 7.39) MPa] was significantly lower than those of the other aging groups with artificial saliva storage[(29.72 ± 6.51) MPa] and thermocycling [(31.92 ± 11.87) MPa, P < 0.05]. There were no differences in the nanoleakage values among the three aging groups (P > 0.05).
All the aging treatments with artificial saliva storage, thermocycling and bacteria aggression could accelerate the degradation of bonding interfaces between an etch-and-rinse adhesive and dentin. Bacteria aggression showed the most impairing effect on the stability of resin-dentin bonds.

In the present paper, the authors calculated the plasma's peak electron temperatures under different heat source separation distance in laser- pulse GMAW hybrid welding based on Boltzmann spectrometry. Plasma's peak electron densities under the corresponding conditions were also calculated by using the Stark width of the plasma spectrum. Combined with high-speed photography, the effect of heat source separation distance on electron temperature and electron density was studied.Read More

The results show that with the increase in heat source separation distance, the electron temperatures and electron densities of laser plasma did not changed significantly. However, the electron temperatures of are plasma decreased, and the electron densities of are plasma first increased and then decreased.

Chlorophyll concentration and photosynthesis activity fluorescence parameters of Chlorella pyrenoidosa stressed by different concentrations of Cd2+ were measured based on algal growth inhibition tests and photosynthetic activity inhibition tests. The relationship between the algal photosynthetic activity inhibition rate and 96 h inhibition rate of specific growth rate at different Cd2+ stress times was studied by sigmoidal curve fitting and one-way ANOVA analysis. The result shows that S function relevance exists between the algal photosynthetic activity inhibition rates for 48 h, 53 h, 72 h, 77 h and 96 h respectively and 96 h inhibition rate of specific growth rate (R2 > 0.Read More

95). Consequently, EC10 (10% effective concentration) after 48 h and 53 h inhibition in photosynthetic activity inhibition tests could be used to represented EC50 (50% effective concentration) in 96 h algal growth inhibition tests for evaluating the Cd2+ toxicity. Dose-response relationships between the algal photosynthetic activity inhibition rates after 48 h and 53 h inhibition and Cd2+ toxic equivalency quantity were further analyzed. The method provided a rapid and viable new thought to monitoring single Cd2+ toxicity in lab and early warn integrated toxicity of pollution in water.

2014Apr

To compare the distribution and concentration of matrix metalloproteinases-2 (MMP-2) in different dentin depth of premolar and molar of young people.
Freshly extracted human premolars and molars (aged between 20-30) were sectioned to 1.5 mm thick slices along the longitudinal axis of the tooth separately.Read More

Enamel and pulp of each slice was removed, and then the premolar and molar slices were respectively divided into two subgroups according to superficial or deep dentin and pulverized to fine powder. After dentin protein was extracted, the concentrations of MMP-2 in different tooth were detected using fluorescent microsphere immunoassay.
The content of MMP-2 in superficial layer dentin of premolar was (0.022 ± 0.006) ng/mg. The content of MMP-2 in deep layer dentin of premolar was (2.087 ± 0.090) ng/mg. The content of MMP-2 in superficial layer dentin of molar was (0.336 ± 0.037) ng/mg. The content of MMP-2 in deep layer dentin of molar was (3.312 ± 0.308) ng/mg.
MMP-2 exists in human coronal dentin. In the same type of teeth of young people, the concentration of MMP-2 in deep dentin was significant higher than those in superficial dentin. In the same dentin depth, the concentration of MMP-2 in molar was significant higher than those in premolar.

This is an expert consensus on the evaluation and treatment of thoracolumbar spinal injury, established from February 2009 to July 2010. The expert consensus consists mainly of six parts with a total of 54 recommendations including the overview (one item); pre-hospital care (one item); evaluation and diagnosis (13 items); treatment (23 items); prevention and treatment of major complications (12 items); and rehabilitation (four items). This is the first time that Chinese experts have published a consensus on spine and spinal cord injury.Read More

The expert consensus was established based on Delphi methods, literature analysis, and clinical experiences. Each recommendation is supported by and was interpreted using multi-level evidences. The level of agreement with the recommendation among the panel members was assessed as either low, moderate, or strong. Each panel member was asked to indicate his or her level of agreement on a 5-point scale, with "1" corresponding to neutrality and "5" representing maximum agreement. Scores were aggregated across the panel members and an arithmetic mean was calculated. This mean score was then translated into low, moderate, or strong. After all of the votes were collected and calculated, the results showed no low-level recommendations, 10 moderate-level recommendations, and 44 strong-level recommendations. An expert consensus was reached and was recognized by Chinese spine surgeons. Wide-scale adoption of these recommendations is urgent in the management of acute thoracolumbar spine and spinal cord injury in a broader attempt to create a standard evaluation and treatment strategy for acute thoracolumbar spine and spinal cord injury in China.