Publications by authors named "Long Ma"

417 Publications

Pathogenesis and therapeutic strategy in platinum resistance lung cancer.

Biochim Biophys Acta Rev Cancer 2021 Jun 4;1876(1):188577. Epub 2021 Jun 4.

Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

Platinum compounds (cisplatin and carboplatin) represent the most active anticancer agents in clinical use both of lung cancer in mono-and combination therapies. However, platinum resistance limits its clinical application. It is necessary to understand the molecular mechanism of platinum resistance, identify predictive markers, and develop newer, more effective and less toxic agents to treat platinum resistance in lung cancer. Here, it summarizes the main molecular mechanisms associated with platinum resistance in lung cancer and the development of new approaches to tackle this clinically relevant problem. Moreover, it could lead to the development of more effective treatment for refractory lung cancer in future.
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http://dx.doi.org/10.1016/j.bbcan.2021.188577DOI Listing
June 2021

Evaluation of candidate reference genes for gene expression analysis in the brassica leaf beetle, Phaedon brassicae (Coleoptera: Chrysomelidae).

PLoS One 2021 3;16(6):e0251920. Epub 2021 Jun 3.

Institute of Entomology, Jiangxi Agricultural University, Nanchang, China.

The brassica leaf beetle Phaedon brassicae is a notorious defoliator of cruciferous vegetables. However, few molecular studies of this pest have been conducted due to limited sequence data. Recently, RNA sequencing has offered a powerful platform to generate numerous transcriptomic data, which require RT-qPCR to validate target gene expression. The selection of reliable reference genes to normalize RT-qPCR data is a prerequisite for gene expression analysis. In the present study, the expression stabilities of eight candidate reference genes under biotic conditions (development stages and various tissues) and abiotic perturbations (thermal stress and pesticide exposure) were evaluated using four different statistical algorithms. The optimal suites of reference genes were recommended for the respective experimental conditions. For tissue expression analysis, RPL32 and EF-1α were recommended as the suitable reference genes. RPL19 and TBP were the optimal reference genes across different developmental stages. RPL32 and TBP were identified as the most suitable references for thermal stress. Furthermore, RPL32 and RPL19 were ranked as the best references for insecticide exposure. This work provides a systematic exploration of the optimal reference genes for the respective experimental conditions, and our findings would facilitate molecular studies of P. brassicae.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251920PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174695PMC
June 2021

Response relationships between abrupt seasonal temperature changes/warming (cooling) hiatuses in China and their influencing factors.

Environ Sci Pollut Res Int 2021 May 14. Epub 2021 May 14.

College of Water Conservancy and Civil Engineering College, Inner Mongolia Agricultural University, Hohhot, 010018, China.

The mechanisms of abrupt seasonal temperature changes and warming (cooling) hiatuses remain unclear. Clarifying how they respond to various influencing factors is critically important to understanding their mechanisms. In this study, the influencing factors to which the abrupt changes in T, T, and T were most sensitive followed the order of (AGG and CO) > SR > WS > AMO > PDO > MEI > AO > AP > RH. Seasonal Tav had the greatest sensitivity to all influencing factors, followed by seasonal Tav and lastly by seasonal T. An abrupt temperature change occurred when AGG, AMO, or SR increased continuously to a certain value, when PDO was in a positive phase (warm phase) and increased continuously to a certain value, when MEI changed abruptly, when WS and RH continued to decline for a certain time and reached a certain tendency rate, or when AP continued to decline for a certain time and reached a certain value. During the period before and after the warming (cooling) hiatuses, the temperature at most of the stations only had a significant relationship with a few influencing factors, and the hiatuses in seasonal T, T, and T were overall most sensitive to changes in WS, followed by changes in RH and lastly by changes in AP. The occurrence of warming (cooling) hiatuses was highly consistent with the variation trend of some influencing factors, which to some extent affected the warming (cooling) hiatuses. Abrupt seasonal temperature changes/warming (cooling) hiatuses are the combined effects of multiple influencing factors.
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http://dx.doi.org/10.1007/s11356-021-14190-0DOI Listing
May 2021

Mental Well-Being in UK Higher Education During Covid-19: Do Students Trust Universities and the Government?

Front Public Health 2021;9:646916. Epub 2021 Apr 26.

Department of Sociology, Oklahoma State University, Stillwater, OK, United States.

This paper draws upon the concept of recreancy to examine the mental well-being of university students during the Covid-19 pandemic. Briefly, recreancy is loss of societal trust that results when institutional actors can no longer be counted on to perform their responsibilities. Our study of mental well-being and recreancy focuses on the role of universities and government regulators within the education sector. We surveyed 600 UK students attending 161 different public higher education providers in October 2020 during a time when many UK students were isolated in their residences and engaged in online learning. We assessed student well-being using the Short Warwick-Edinburgh Mental Well-being Scale (scored 7-35) and found the mean score to be 19.9 [95% confidence interval (CI) 19.6, 20.2]. This level of well-being indicates that a significant proportion of UK students face low levels of mental well-being. Structural equation modeling (SEM) analysis indicates that high recreancy-measured as a low trust in universities and the government-is associated with low levels of mental well-being across the student sample. While these findings are suggestive, they are also important and we suggest that government and university leaders should not only work to increase food and housing security during the Covid-19 pandemic, but also consider how to combat various sector trends that might intensify recreancy.
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http://dx.doi.org/10.3389/fpubh.2021.646916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107392PMC
May 2021

Long-term safety, efficacy, and tolerability of levetiracetam in pediatric patients with epilepsy in Uygur, China: A retrospective analysis.

Epilepsy Behav 2021 Jul 5;120:108010. Epub 2021 May 5.

Department of Pharmacy, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Province 830001, China; Institute of Clinical Pharmacy, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Province 830001, China. Electronic address:

Purpose: Levetiracetam is approved as an add-on therapy to treat refractory partial seizures in pediatric patients over four years old. The efficacy and safety in pediatric patients with epilepsy in Uygur, China, is unknown. Therefore, the objective of this study was to investigate the safety, efficacy, and tolerability of levetiracetam in pediatric patients with epilepsy in Uygur, China.

Methods: This retrospective study compared the efficacy and safety of levetiracetam monotherapy and in combination with other antiseizure medications (ASMs) in 1055 pediatric patients with epilepsy treated with levetiracetam. The seizure frequencies at 1, 2, and 3 years after starting levetiracetam therapy were recorded and compared with the baseline yearly frequency. Safety variables included the incidence and type of adverse reactions.

Results: A total of 680 (64%) pediatric patients responded to levetiracetam therapy with a more than 50% reduction in the frequency of seizures. Seizure-free rates increased over time, 13%, 15%, and 18% at 1, 2, and 3 years, respectively. The number of baseline ASMs and the order of levetiracetam introduction were highly significant, impacting the likelihood of seizure remission during a 3-year follow-up period (p < 0.001). During levetiracetam treatment, 233 pediatric patients (22%) experienced at least one adverse reaction.

Conclusion: These significant findings indicate that levetiracetam is likely to become a widely prescribed ASM for epilepsy in pediatric clinical practice because of its long-term safety, efficacy, and tolerability.
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http://dx.doi.org/10.1016/j.yebeh.2021.108010DOI Listing
July 2021

NR4A1 knockdown confers hepatoprotection against ischaemia-reperfusion injury by suppressing TGFβ1 via inhibition of CYR61/NF-κB in mouse hepatocytes.

J Cell Mol Med 2021 Jun 3;25(11):5099-5112. Epub 2021 May 3.

Department of Intensive Care Unit, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.

Nuclear receptor subfamily 4, group A, member 1 (NR4A1) can aggravate ischaemia-reperfusion (I/R) injury in the heart, kidney and brain. Thus, the present study aimed to unravel the role of NR4A1 on hepatic I/R injury. For this purpose, the mouse hepatic I/R model and H/R-exposed mouse hepatocytes model were established to stimulate the hepatic and hepatocellular damage. Then, the levels of ALT and AST as well as TNF-α and IL-1β expression were measured in the mouse serum and supernatant of hepatocyte s, respectively. Thereafter, we quantified the levels of NR4A1, CYR61, NF-kB p65 and TGFβ1 under pathological conditions, and their interactions were analysed using ChIP and dual-luciferase reporter gene assays. The in vivo and in vitro effects of NR4A1, CYR61, NF-kB p65 and TGFβ1 on I/R-induced hepatic and H/R-induced hepatocellular damage were evaluated using gain- and loss-of-function approaches. NR4A1 was up-regulated in the hepatic tissues of I/R-operated mice and in H/R-treated hepatocytes. Silencing NR4A1 relieved the I/R-induced hepatic injury, as supported by suppression of ALT and AST as well as TNF-α and IL-1β. Meanwhile, NR4A1 knockdown attenuated the H/R-induced hepatocellular damage by inhibiting the apoptosis of hepatocyte s. Moreover, we also found that NR4A1 up-regulated the expression of CYR61 which resulted in the activation of the NF-κB signalling pathway, thereby enhancing the transcription of TGFβ1, which was validated to be the mechanism underlying the contributory role of NR4A1 in hepatic I/R injury. Taken together, NR4A1 silencing reduced the expression of CYR61/NF-κB/TGFβ1, thereby relieving the hepatic I/R injury.
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http://dx.doi.org/10.1111/jcmm.16493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178266PMC
June 2021

Learning Deep Context-Sensitive Decomposition for Low-Light Image Enhancement.

IEEE Trans Neural Netw Learn Syst 2021 Apr 30;PP. Epub 2021 Apr 30.

Enhancing the quality of low-light (LOL) images plays a very important role in many image processing and multimedia applications. In recent years, a variety of deep learning techniques have been developed to address this challenging task. A typical framework is to simultaneously estimate the illumination and reflectance, but they disregard the scene-level contextual information encapsulated in feature spaces, causing many unfavorable outcomes, e.g., details loss, color unsaturation, and artifacts. To address these issues, we develop a new context-sensitive decomposition network (CSDNet) architecture to exploit the scene-level contextual dependencies on spatial scales. More concretely, we build a two-stream estimation mechanism including reflectance and illumination estimation network. We design a novel context-sensitive decomposition connection to bridge the two-stream mechanism by incorporating the physical principle. The spatially varying illumination guidance is further constructed for achieving the edge-aware smoothness property of the illumination component. According to different training patterns, we construct CSDNet (paired supervision) and context-sensitive decomposition generative adversarial network (CSDGAN) (unpaired supervision) to fully evaluate our designed architecture. We test our method on seven testing benchmarks [including massachusetts institute of technology (MIT)-Adobe FiveK, LOL, ExDark, and naturalness preserved enhancement (NPE)] to conduct plenty of analytical and evaluated experiments. Thanks to our designed context-sensitive decomposition connection, we successfully realized excellent enhanced results (with sufficient details, vivid colors, and few noises), which fully indicates our superiority against existing state-of-the-art approaches. Finally, considering the practical needs for high efficiency, we develop a lightweight CSDNet (named LiteCSDNet) by reducing the number of channels. Furthermore, by sharing an encoder for these two components, we obtain a more lightweight version (SLiteCSDNet for short). SLiteCSDNet just contains 0.0301M parameters but achieves the almost same performance as CSDNet. Code is available at https://github.com/KarelZhang/CSDNet-CSDGAN.
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http://dx.doi.org/10.1109/TNNLS.2021.3071245DOI Listing
April 2021

Delayed Anastomotic Occlusion after Direct Revascularization in Adult Hemorrhagic Moyamoya Disease.

Brain Sci 2021 Apr 24;11(5). Epub 2021 Apr 24.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.

Delayed anastomotic occlusion occurred in a considerable proportion of hemorrhagic moyamoya disease (MMD) patients undergoing direct revascularization. This study aimed to investigate the predictors and outcomes of delayed anastomotic occlusion in adult hemorrhagic MMD. The authors retrospectively reviewed 87 adult hemorrhagic MMD patients. Univariate and multivariate logistic regression analyses were performed. After an average of 9.1 ± 6.9 months of angiographic follow-up, the long-term graft patency rates were 79.8%. The occluded group had significantly worse angiogenesis than the non-occluded group ( < 0.001). However, the improvement of dilated anterior choroidal artery-posterior communicating artery was similar ( = 0.090). After an average of 4.0 ± 2.5 years of clinical follow-up, the neurological statues and postoperative annualized rupture risk were similar between the occluded and non-occluded groups ( = 0.750; = 0.679; respectively). In the multivariate logistic regression analysis, collateral circulation Grade III (OR, 4.772; 95% CI, 1.184-19.230; = 0.028) and preoperative computed tomography perfusion (CTP) Grade I-II (OR, 4.129; 95% CI, 1.294-13.175; = 0.017) were independent predictors of delayed anastomotic occlusion. Delayed anastomotic occlusion in adult hemorrhagic MMD might be a benign phenomenon. Good collateral circulation (Grade III) and compensable preoperative intracranial perfusion (CTP Grade I-II) are independent predictors for this phenomenon. Moreover, the delayed anastomotic occlusion has no significant correlations with the long-term angiographic and neurological outcomes, except neoangiogenesis.
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http://dx.doi.org/10.3390/brainsci11050536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145476PMC
April 2021

Effects of double-dose statin therapy for the prevention of post-stroke epilepsy: A prospective clinical study.

Seizure 2021 May 15;88:138-142. Epub 2021 Apr 15.

The Second Affiliated Hospital of Harbin Medical University, China. Electronic address:

Background: To determine treatment effects on the incidence of post-stroke epilepsy (PSE) using different doses of statin, a prospective hospital-based cohort study was designed to explore whether a double-dose statin treatment can better prevent the occurrence of PSE.

Methods: A total of 1152 patients with newly diagnosed ischemic stroke admitted to our hospital from March to August 2017 were selected, 1033 of whom were followed-up. Patients were divided into two treatment groups:(1) standard-dose (20 mg atorvastatin or 10 mg rosuvastatin,daily oral; 788 patients); and (2) double-dose (40 mg atorvastatin or 20 mg rosuvastatin, daily oral; 245 patients).At 18 months follow-up was conducted to compare the incidence of PSE between groups.

Results: In general, in the standard-dose group we observed two cases of early seizure (ES) (0.25%), 22 cases oflate seizure (LS) (2.79%) and 20 cases of PSE (2.54%). In the double-dose group, onepatient had ES (0.41%), two patients had LS (0.82%), and onepatient had PSE (0.41%). The incidence of PSE was significantly lower in the double-dose group as compared to the standard-dose group. There was a higher proportion of PSE in patients younger than 65 years and in males. Three patients had ES; one presented with focal aware seizure (FAS), and two had focal to bilateral tonic-clonic seizure (FBTCS). Among the 21 patients with PSE, there were two cases of FAS, five cases of focal impaired awareness seizure (FIAS), five cases of FBTCS, and nine cases of GTCS, suggesting that partial seizure is the most common type of PSE. Cerebral cortex was involved in 85.75% of cases with PSE, and multiple lobes were involved in 61.9% of cases with PSE.

Conclusion: Increasing the dose of statin treatment during the acute phase of ischemic stroke reduces the incidence of PSE. Further research is needed to understand the mechanisms underlying the potential preventative effects of statins against PSE.
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http://dx.doi.org/10.1016/j.seizure.2021.04.010DOI Listing
May 2021

Extensive cytokine analysis in synovial fluid of osteoarthritis patients.

Cytokine 2021 Jul 22;143:155546. Epub 2021 Apr 22.

Department of Orthopedics, The General Hospital of Ningxia Medical University, PR China. Electronic address:

Objective: Osteoarthritis (OA) is a joint disease characterized by articular cartilage loss and afflicts many people worldwide. However, diagnostic methods and treatment options remain limited and are often characterized by low sensitivity and low efficacy. The focus of the present study was to identify proteomic biomarkers in synovial fluid to improve diagnosis and therapy of OA patients.

Methods: Antibody array technology was utilized for protein expression profiling of synovial fluid from 24 OA patients and 24 healthy persons.

Results: Compared with healthy persons, twenty proteins showed lower expression levels in OA patients, while thirty proteins had higher levels. Among these differential proteins, GITRL, CEACAM-1, FSH, EG-VEGF, FGF-4, PIGF, Cystatin EM and NT-4 were found for the first time to be differentially expressed in OA. Bioinformatics analysis showed that most of these differential proteins were involved leukocytes events, and some differentially expressed proteins including IL-18, CXCL1, CTLA4, MIP-3b, CD40, MMP-1, THBS1, CCL11, PAI-1, BAFF, aggrecan, angiogenin and follistatin were located in central positions of the protein-protein interaction (PPI) network.

Conclusion: We speculate that leukocyte proliferation and migration to the joint may be an important pathogenesis of OA, which needs a further validation. The central proteins of the PPI network may play a more pivotal role in OA. The newly identified differentially expressed proteins may be novel biomarkers for OA diagnosis and targets for OA therapy.
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http://dx.doi.org/10.1016/j.cyto.2021.155546DOI Listing
July 2021

Analysis of the heterogeneity of the BCR H-CDR3 repertoire in the bone marrow and spleen of 3-, 12-, and 20-month old mice.

Immun Ageing 2021 Apr 12;18(1):17. Epub 2021 Apr 12.

Department of Immunology, Center of ImmunoMolecular Engineering, Innovation & Practice Base for Graduate Students Education, Zunyi Medical University, Zunyi City, 563000, China.

The number of central and peripheral B cells and their responsiveness are decreased in aged mice. The diversity of mice central and peripheral B cell repertoires with increasing age has not been elucidated. In this study, we demonstrated that there were significant differences in the usage of some V, D, and J genes in the BCR H-CDR3 repertoire of bone marrow B cells, spleen B cells and spleen memory B cells in 3-, 12-, and 20-month-old mice. In the productive, pseudogene, and out-of-frame sequences, bone marrow B cells had significant differences in 5'J trimming with age; peripheral spleen B cells and memory B cells had significant differences in N1 insertion, N2 insertion, P5'D insertion, and 5'D trimming with age. The BCR H-CDR3 repertoire diversity of mice bone marrow B cells, spleen B cells and spleen memory B cells decreased with increasing age. The proportion of overlap in bone marrow and spleen B cells, but not spleen memory B cells, of mice at different ages was lower at 3 months than at 12 and 20 months. This study is the first to report the homogeneity and heterogeneity of the CDR3 repertoire of central and peripheral B cells change as mice age, to further investigation of the decline and response of B cell immunity in young/middle/old-aged mice.
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http://dx.doi.org/10.1186/s12979-021-00231-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040230PMC
April 2021

Microglial Polarization: Novel Therapeutic Strategy against Ischemic Stroke.

Aging Dis 2021 Apr 1;12(2):466-479. Epub 2021 Apr 1.

1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Ischemic stroke, which is the second highest cause of death and the leading cause of disability, represents ~71% of all strokes globally. Some studies have found that the key elements of the pathobiology of stroke is immunity and inflammation. Microglia are the first line of defense in the nervous system. After stroke, the activated microglia become a double-edged sword, with distinct phenotypic changes to the deleterious M1 types and neuroprotective M2 types. Therefore, ways to promote microglial polarization toward M2 phenotype after stroke have become the focus of attention in recent years. In this review, we discuss the process of microglial polarization, summarize the alternation of signaling pathways and epigenetic regulation that control microglial polarization in ischemic stroke, aiming to find the potential mechanisms by which microglia can be transformed into the M2 polarized phenotype.
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http://dx.doi.org/10.14336/AD.2020.0701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990355PMC
April 2021

lncRNA RPSAP52 induced the development of tongue squamous cell carcinomas via miR-423-5p/MYBL2.

J Cell Mol Med 2021 May 30;25(10):4744-4752. Epub 2021 Mar 30.

Department of Endodontics, Jinan Stomatological Hospital, Jinan, China.

Growing lncRNAs have been noted to involve in the initiation and development of several tumours including tongue squamous cell carcinomas (TSCCs). However, the biological role and mechanism of lncRNA RPSAP52 were not well-explained. We indicated that RPSAP52 was higher in TSCC samples compared with that in control samples. The higher expression of RPSAP52 was positively correlated with higher T stage and TNM stage. Ectopic expression of RPSAP52 induced TSCC cell growth and cycle and induced cytokine secretion including IFN-γ, IL-1β and IL-6, IL-8, IL-10 and TGF-β. We found that the overexpression of RPSAP52 suppressed miR-423-5p expression in SCC-4 cell. miR-423-5p was lower in TSCC samples compared with that in control samples, and miR-423-5p level was negatively correlated with higher T stage and TNM stage. Pearson's correlation indicated that miR-423-5p was negatively associated with that of RPSAP52 in TSCC tissues. Furthermore, MYBL2 was one direct gene of miR-423-5p and elevated expression of miR-423-5p suppressed MYBL2 expression and ectopic expression of RPSAP52 increased MYBL2 expression in SCC-4 cell. Finally, we illustrated that RPSAP52 overexpression promoted TSCC cell growth and cycle and induced cytokine secretion including IFN-γ, IL-1β and IL-6, IL-8, IL-10 and TGF-β via modulating MYBL2. These data provided new insight into RPSAP52, which may be one potential treatment target for TSCC.
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http://dx.doi.org/10.1111/jcmm.16442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107108PMC
May 2021

Extravascular Lung Water and Intrathoracic Blood Volume Index Are Associated With Liver Function in Brain Dead Donors for Organ Transplant.

Exp Clin Transplant 2021 May 18;19(5):450-456. Epub 2021 Mar 18.

From the Department of Neurointensive Care Medicine, The First Affiliated Hospital of Xinjiang Medical University, Beijing.

Objectives: Hemodynamic measurements during organ transplant procedures are essential.

Materials And Methods: In this observational study, we measured clinical and hemodynamic parameters in 11 patients with advanced pulse indicator continuous cardiac output monitoring. Normally distributed clinical data were calculated as means ± standard deviation; hemodynamic, metabolic, and respiratory parameters related to liver and renal function were compared by linear regression analysis using Pearson correlation.

Results: Compared with the normal range, systemic vascular resistance was high (2278.02 ± 719.6 dyne·s/cm²/m²) and intrathoracic blood volume was low (787.37 ± 224.01 mL/m²) in our patient group. C-reactive protein and interleukin 6 levels were 96.26 ± 68.10 mg/mL and 246.24 ± 355.74 mmol/L, respectively. Liver and renal function parameters were in normal ranges. Extravascular lung water was correlated with total, conjugated, and unconjugated bilirubin and albumin (r = 0.342/P = .005; r = 0.338/ P = .005; r = 0.394/P = .001, and r = 0.358/P = .003) but not with aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and serum creatinine. Intrathoracic blood volume index was correlated with total bilirubin, unconjugated bilirubin, and albumin (r = 0.324/P = .007; r = 0.394/P = .001, and r = 0.296/P = .015) but not with conjugated bilirubin, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and serum creatinine. Lactate was not correlated with total bilirubin, unconjugated bilirubin, albumin, and serum creatinine, but base excess was correlated with total bilirubin, unconjugated bilirubin, alanine aminotransferase, and albumin. PO₂ and Pco₂ were not correlated with liver function, although PO₂ was correlated with albumin.

Conclusions: No correlations were shown between intrathoracic blood volume index, extravascular lung water, and liver function, but metabolic parameters, including base excess and lactate, were correlated with liver function. Pulse indicator continuous cardiac output monitoring may be a useful method to assess organ function and tissue perfusion in organ transplant.
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http://dx.doi.org/10.6002/ect.2020.0492DOI Listing
May 2021

Downregulation of miR-497-5p prevents liver ischemia-reperfusion injury in association with MED1/TIMP-2 axis and the NF-κB pathway.

FASEB J 2021 Apr;35(4):e21180

Department of Critical Care Medicine, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, P. R. China.

Liver ischemia-reperfusion (I/R) injury is a common clinical pathological phenomenon, which is accompanied by the occurrence in liver transplantation. However, the underlying mechanism is not yet fully understood. MicroRNAs (miRNAs) play an important role in liver I/R injury. Therefore, the study of miRNAs function will contribute a new biological marker diagnosis of liver I/R injury. This study aims to evaluate effects of miR-497-5p in liver I/R injury in mice. The related regulatory factors of miR-497-5p in liver I/R injury were predicted by bioinformatics analysis. Vascular occlusion was performed to establish the liver I/R injury animal models. Hypoxia/reoxygenation (H/R) was performed to establish the in vitro models. Hematoxylin-eosin (HE) staining was conducted to assess liver injury. The inflammatory factors were evaluated by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was adopted to assess the cell apoptosis. The expression of miR-497b-5p was increased in liver I/R injury. Knockdown of miR-497b-5p inhibited the production of inflammatory factors and cell apoptosis. Overexpression of mediator complex subunit 1 (MED1) and tissue inhibitor of metalloproteinase 2 (TIMP2) inhibited cell apoptosis to alleviate liver I/R injury. miR-497b-5p could activate the nuclear factor kappa-B (NF-κB) pathway by inhibiting the MED1/TIMP-2 axis to promote liver I/R injury. This study may provide a new strategy for the treatment of liver I/R injury.
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http://dx.doi.org/10.1096/fj.202001029RDOI Listing
April 2021

Pediatric Index of Mortality 3-An Evaluation of Function Among ICUs In South Africa.

Pediatr Crit Care Med 2021 Mar 10. Epub 2021 Mar 10.

Department of Paediatrics and Child Health, University of the Free State Faculty of Health Sciences School of Medicine Bloemfontein, South Africa. Paediatric Intensive Care Units, Universitas Academic and Pelonomi Tertiary Hospitals, Bloemfontein, South Africa. Division of Critical Care and Chris Hani Baragwanath Academic Hospital Paediatric Intensive Care Unit, University of the Witwatersrand School of Medicine, Johannesburg, South Africa. Department of Paediatrics and Child Health, Tygerberg Hospital Paediatric Intensive Care Unit and the University of Stellenbosch Faculty of Medicine and Health Sciences, Stellenbosch, South Africa. Department of Paediatrics and Child Health and Steve Biko Academic Hospital Paediatric Intensive Care Unit, University of Pretoria School of Medicine, Pretoria, South Africa. Department of Cardiothoracic Surgery, University of the Free State Faculty of Health Sciences School of Medicine, Bloemfontein, South Africa. Cardiothoracic Intensive Care Unit, Universitas Academic Hospital, Bloemfontein, South Africa. Department of Paediatrics and Child Health and Red Cross War Memorial Children's Hospital Intensive Care Unit, University of Cape Town, Cape Town, South Africa. Paediatric Intensive Care Unit, Greys Hospital, Pietermaritzberg, South Africa. Department of Paediatrics, Nkosi Albert Luthuli Academic Hospital Paediatric Intensive Care Unit and the University of Kwazulu Natal School of Medicine, Durban, South Africa.

Objectives: To evaluate the performance of the Pediatric Index of Mortality 3 as mortality risk assessment model.

Design: This prospective study included all admissions 30 days to 18 years old for 12 months during 2016 and 2017. Data gathered included the following: age and gender, diagnosis and reason for PICU admission, data specific for the Pediatric Index of Mortality 3 calculation, PICU outcomes (death or survival), and length of PICU stay.

Setting: Nine units that care for children within tertiary or quaternary academic hospitals in South Africa.

Patients: All admissions 30 days to 18 years old, excluding premature infants, children who died within 2 hours of admission, or children transferred to other PICUs, and those older than 18 years old.

Interventions: None.

Measurements And Main Results: There were 3,681 admissions of which 2,253 (61.3%) were male. The median age was 18 months (interquartile range, 6-59.5 mo). There were 354 deaths (9.6%). The Pediatric Index of Mortality 3 predicted 277.47 deaths (7.5%). The overall standardized mortality ratio was 1.28. The area under the receiver operating characteristic curve was 0.81 (95% CI 0.79-0.83). The Hosmer-Lemeshow goodness-of-fit test statistic was 174.4 (p < 0.001). Standardized mortality ratio for all age groups was greater than 1. Standardized mortality ratio for diagnostic subgroups was mostly greater than 1 except for those whose reason for PICU admission was classified as accident, toxin and envenomation, and metabolic which had an standardized mortality ratio less than 1. There were similar proportions of respiratory patients, but significantly greater proportions of neurologic and cardiac (including postoperative) patients in the Pediatric Index of Mortality 3 derivation cohort than the South African cohort. In contrast, the South African cohort contained a significantly greater proportion of miscellaneous (including injury/accident victims) and postoperative noncardiac patients.

Conclusions: The Pediatric Index of Mortality 3 discrimination between death and survival among South African units was good. Case-mix differences between these units and the Pediatric Index of Mortality 3 derivation cohort may partly explain the poor calibration. We need to recalibrate Pediatric Index of Mortality 3 to the local setting.
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http://dx.doi.org/10.1097/PCC.0000000000002693DOI Listing
March 2021

A novel homozygous nonsense mutation in zona pellucida 1 (ZP1) causes human female empty follicle syndrome.

J Assist Reprod Genet 2021 Mar 5. Epub 2021 Mar 5.

State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.

Purpose: To identify a pathogenic gene mutation in a female infertility proband characterized by empty follicle syndrome (EFS) and explore the genetic cause of EFS.

Methods: Whole exome sequencing (WES) was performed to identify the candidate pathogenic mutation. Sanger sequencing was used to validate the mutation in family members. The pathogenicity of the identified variant and its possible effects on the protein were evaluated with in silico tools. Immunofluorescence staining was used to study the possible mechanism of the mutation on affected oocyte.

Results: We identified a family with a novel homozygous nonsense mutation in zona pellucida 1 (ZP1) (c.199G > T [p.Glu67Ter]). Based on bioinformatics analysis, the mutation was predicted to be pathogenic. This variant generates a premature stop codon in exon 2 at the 199th nucleotide, and was inferred to result in a truncated ZP1 protein of 67 amino acids at the ZP-N1 domain. An in vitro study showed that the oocyte of the EFS proband was degenerated and the zona pellucida was absent. Additionally, the mutant ZP1 proteins were localized in the cytoplasm of the degenerated oocyte but not at the surface.

Conclusions: The novel mutation in ZP1 is a genetic cause of female infertility characterized by EFS. Our finding expands the genetic spectrum for EFS and will help justify the EFS diagnosis in patients.
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http://dx.doi.org/10.1007/s10815-021-02136-xDOI Listing
March 2021

Fluoxetine, a selective serotonin reuptake inhibitor used clinically, improves bladder function in a mouse model of moderate spinal cord injury.

Neural Regen Res 2021 Oct;16(10):2093-2098

Department of Urology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.

After spinal cord injury, the upward conduction of the spinal cord is lost, resulting in the loss of micturition control, which manifests as detrusor sphincter dyssynergia and insufficient micturition. Studies have shown that serotonergic axons play important roles in the control of the descending urination tract. In this study, mouse models of moderate spinal cord contusions were established. The serotonin agonists quipazine (0.2 mg/kg), 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DAPT, 0.1 mg/kg), buspirone (1 mg/kg), sumatriptan (1 mg/kg), and rizatriptan (50 mg/kg), the serotonin reuptake inhibitors fluoxetine (20 mg/kg) and duloxetine (1 mg/kg), and the dopamine receptor agonist SKF-82197 (0.1 mg/kg) were intraperitoneally administered to the model mice 35 days post-injury in an acute manner. The voided stain on paper method and urodynamics revealed that fluoxetine reduced the amount of residual urine in the bladder and decreased bladder and external urethral sphincter pressure in a mouse model of moderate spinal cord injury. However, fluoxetine did not improve the micturition function in a mouse model of severe spinal cord injury. In contrast, the other serotonergic drugs had no effects on the micturition functions of spinal cord injury model mice. This study was ethically approved by the Institutional Animal Care and Use Committee of Jiangsu Province Hospital of Chinese Medicine (approval No. 2020DW-20-02) on September 11, 2020.
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http://dx.doi.org/10.4103/1673-5374.308667DOI Listing
October 2021

Potential and promising anticancer drugs from adenosine and its analogs.

Drug Discov Today 2021 Jun 25;26(6):1490-1500. Epub 2021 Feb 25.

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China. Electronic address:

In recent years, many studies have shown that adenosine has efficacy for treating cancer. More importantly, some adenosine analogs have been successfully marketed to fulfill anticancer purposes. In this review, we summarize the anticancer effects of adenosine and its analogs in clinical trials and preclinical studies, with focus on their anticancer mechanisms. In addition, we link the anticancer activities of adenosine analogs with their structures through structure-activity relationship (SAR) analysis, and highlight additional promising anticancer drug candidates. We hope that this review will be of help in understanding the importance of adenosine and its analogs with anticancer activities and directing future research and development of such compounds.
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http://dx.doi.org/10.1016/j.drudis.2021.02.020DOI Listing
June 2021

Safety, efficacy, and tolerability of lacosamide for the treatment of epilepsy in pediatric patients in Uygur, China.

Epilepsy Behav 2021 04 18;117:107814. Epub 2021 Feb 18.

Department of Pharmacy, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Province 830001, China; Institute of Clinical Pharmacy, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Province 830001, China. Electronic address:

Purpose: Lacosamide (LCM) was approved in China in 2018. However, the safety of LCM has not been established in pediatric patients. Therefore, the objective of this study was to investigate its safety, efficacy, and tolerability in pediatric patients living in Uygur, Northwest China.

Methods: This is a retrospective analysis of pediatric patients diagnosed with epilepsy and on LCM therapy at a medical center. The seizure frequencies at 3, 6, and 12 months after starting LCM therapy were recorded and compared with the baseline monthly frequency. The primary outcome variables were the 50% responder and seizure-free rates. The secondary outcome variables included the terminal 6-month seizure remission and percentages of discontinuation due to a lack of efficacy and tolerability. Safety variables included the incidence and type of adverse reactions.

Results: Seventy-two pediatric patients with epilepsy living in Uygur, China and receiving LCM treatment were included in the present study. Fifty (69%) children responded to LCM therapy with a more than 50% reduction in the frequency of seizures. Seizure-free rates increased over time, at 14%, 19%, and 20% at 3, 6, and 12 months, respectively. The number of baseline anti-seizure medications (ASMs) and order of LCM introduction significantly impacted the likelihood of seizure remission during the 12-month follow-up period (p < 0.05). During the entire period of LCM treatment, twenty-two children (30.5%) experienced at least one adverse reaction.

Conclusion: This retrospective study of 72 pediatric patients with epilepsy in Uygur, China, showed that LCM therapy is safe and effective for epilepsy in children, resulting in a reduction in the seizure rate.
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http://dx.doi.org/10.1016/j.yebeh.2021.107814DOI Listing
April 2021

Effect of sample volume on the sensitivity of lateral flow assays through computational modeling.

Anal Biochem 2021 04 16;619:114130. Epub 2021 Feb 16.

Academy of Opto-electric Technology, Hefei University of Technology, Special Display and Imaging Technology Innovation Center of Anhui Province, State Key Laboratory of Advanced Display Technology, 193 Tunxi Road, Hefei, 230009, China.

Lateral flow assays (LFAs) are extensively used in qualitative detection because of their convenience, low cost, fast results, and ease of operation. However, the sample volume used in a lateral flow assay is usually determined experimentally. We test and find that the flow velocity is influenced by sample volume, using fluorescent microspheres as label particles, when analyte concentration is fixed in a sandwich LFA. A model is developed based on mass-action kinetics and advection-diffusion-reaction equation, combing the conjugate pad and nitrocellulose membrane. The model shows predictions from 10 to 120 μL, and predicts accurately the experimental results from 50 to 120 μL where the fluid can flow to the test line. Over all, the model can provide predictions over a wide range of sample volumes for sensitivity analysis. On the basis of the model, the sensitivity of the LFA can be improved according to the sample volume added in the experiment.
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http://dx.doi.org/10.1016/j.ab.2021.114130DOI Listing
April 2021

Effect of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on reproductive system.

Stem Cell Res 2021 04 4;52:102189. Epub 2021 Feb 4.

Reproductive Medicine Center, The First Affiliated Hospital of China Naval Military Medical University, Shanghai, People's Republic of China. Electronic address:

Since the emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in December 2019, it has rapidly spread across many countries and it has become a crucial global health concern. Furthermore, SARS-CoV-2 infection not only effect on respiratory system, but on reproductive system of human. However, there has been not any review described the transmission paths and effects of SARS-CoV-2 infection on human reproductive system, systematically. In order to describe the transmission paths of SARS-CoV-2, effect on the male/female reproductive system of SARS-CoV-2 and some successful prevention measures. We would like to review effect of SARS-CoV-2 on reproductive system. To conclude, SARS-CoV-2 infection might damage to male reproductive system via ACE2 receptor mediating and male patients were reportedly slightly more affected than women by SARS-CoV-2 infections.
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http://dx.doi.org/10.1016/j.scr.2021.102189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858002PMC
April 2021

Mitigation of acute radiation-induced brain injury in a mouse model using anlotinib.

Ann Palliat Med 2021 Jan;10(1):312-322

Department of Oncology, Binzhou Medical University Hospital, Binzhou, China. Email:

Background: With the development of radiological technologies, radiotherapy has been gradually widely used in the clinic to intracranial tumours and become standardised. However, the related central nervous system disorders are still the most obvious complications after radiotherapy. This study aims to quantify the effectiveness of anlotinib, a small molecule inhibitor of multiple receptor tyrosine kinases, in mitigating acute phase of radiation-induced brain injury (RBI) in a mouse model.

Methods: The onset and progression of RBI were investigated in vivo. All mice, (except for the sham group) were irradiated at a single-fraction of 20 Gy and treated with different doses of anlotinib (0, 0.2 and 0.8 mg/kg, respectively). The expression levels of glial fibrillary acidic protein (GFAP), hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and phosphorylated vascular endothelial growth factor receptor-2 (p-VEGFR2) were assessed by western blot. Histological changes were identified by luxol fast blue (LFB) staining.

Results: The expression levels of GFAP, HIF-1α, and VEGF were downregulated following treatment with anlotinib. However, anlotinib failed to inhibit the development of demyelination. Cerebral edema [as measured by brain water content (BWC)] was also mitigated following treatment with anlotinib.

Conclusions: In summary, treatment with anlotinib significantly mitigated the adverse effects of acute RBI in a dose-dependent manner by downregulating the activation of astrocytes, improving brain hypoxia, and alleviating cerebral edema.
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http://dx.doi.org/10.21037/apm-20-2284DOI Listing
January 2021

Underexposed Image Correction via Hybrid Priors Navigated Deep Propagation.

IEEE Trans Neural Netw Learn Syst 2021 Jan 29;PP. Epub 2021 Jan 29.

Enhancing visual quality for underexposed images is an extensively concerning task that plays an important role in various areas of multimedia and computer vision. Most existing methods often fail to generate high-quality results with appropriate luminance and abundant details. To address these issues, we develop a novel framework, integrating both knowledge from physical principles and implicit distributions from data to address underexposed image correction. More concretely, we propose a new perspective to formulate this task as an energy-inspired model with advanced hybrid priors. A propagation procedure navigated by the hybrid priors is well designed for simultaneously propagating the reflectance and illumination toward desired results. We conduct extensive experiments to verify the necessity of integrating both underlying principles (i.e., with knowledge) and distributions (i.e., from data) as navigated deep propagation. Plenty of experimental results of underexposed image correction demonstrate that our proposed method performs favorably against the state-of-the-art methods on both subjective and objective assessments. In addition, we execute the task of face detection to further verify the naturalness and practical value of underexposed image correction. What is more, we apply our method to solve single-image haze removal whose experimental results further demonstrate our superiorities.
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http://dx.doi.org/10.1109/TNNLS.2021.3052903DOI Listing
January 2021

Nose-to-brain delivery of disulfiram nanoemulsion in situ gel formulation for glioblastoma targeting therapy.

Int J Pharm 2021 Mar 22;597:120250. Epub 2021 Jan 22.

Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China. Electronic address:

Glioblastoma (GBM) is a difficult-to-treat cancer, likely attributed to the blood brain barrier and drug resistance. Nose-to-brain drug delivery is a direct and non-invasive pathway for brain targeting with low systemic toxicity. Disulfiram (DSF) has shown its effectiveness against GBM, especially with copper ion (Cu). In this work, we designed a DSF loaded ion-sensitive nanoemulsion in situ gel (DSF-INEG) that was delivered intranasally along with Cu to the rat brains for the GBM treatment. The developed DSF-INEG nanomedicine showed a suitable particle size of 63.4 ± 1.1 nm and zeta potential of -23.5 ± 0.2 mV with a favorable gelling ability and prolonged DSF release. The results in vitro indicate DSF-INEG/Cu effectively inhibited the proliferation of both C6 and U87 cells. Besides, the excellent brain-targeting efficacy via nose-to-brain delivery was proved by the highest fluorescence signal of Cy5.5-INEG in the rat brains. Moreover, GFP imaging showed enhanced tumor growth inhibition of the rats by the DSF-INEG/Cu treatment, and their median survival time was 1.6 and 1.2 folds than those of the rats in the control and DSF/Cu treated groups, respectively, with no obvious histopathological damage to normal tissues. Overall, DSF-INEG/Cu could be a promising intranasal nanomedicine for effective GBM treatment.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120250DOI Listing
March 2021

Effect of Spectral Signal-to-Noise Ratio on Resolution Enhancement at Surface Plasmon Resonance.

Sensors (Basel) 2021 Jan 18;21(2). Epub 2021 Jan 18.

School of Instrument Science and Opto-Electronics Engineering, Hefei University of Technology, Hefei 230009, China.

Refractive index resolution is an important indicator for a wavelength interrogation surface plasmon resonance sensor, which can be affected by signal-to-noise ratio. This paper investigates the impact of spectral signal-to-noise ratio on a surface plasmon resonance sensor. The effects of different spectral powers and noises are compared and verified through simulation and experiments. The results indicate that the optimal resonance wavelength is changed and the refractive index resolution can even be nearly twice as good when the spectral signal-to-noise ratio is increased. The optimal resonance wavelength can be found by changing the spectral power distribution or noise.
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http://dx.doi.org/10.3390/s21020641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831335PMC
January 2021

Polyphenol-Rich Extract from Seeds Alleviates Hypertension-Induced Renal Damage in Rats.

J Agric Food Chem 2021 Feb 20;69(7):2138-2148. Epub 2021 Jan 20.

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Laboratory of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.

seed is a valuable byproduct of the subtropical fruit litchi ( Sonn.), whose extract (LSE) has been confirmed to ameliorate dyslipidemia, hyperglycemia, and oxidative stress caused by type 2 diabetes. However, if LSE exerts an effect on anti-hypertension and hypertensive renal damage remains unknown. In this study, 13 polyphenols and one fatty acid were identified by UPLC-Q/TOF-MS. Network pharmacological analysis revealed that the therapeutic effects of LSE may be involved in multitargets and multipathways, such as the TNF signaling pathway, interleukin (IL)-6-mediated signaling pathway, NF-kappa B signaling pathway, removal of superoxide radicals, negative regulation of blood pressure, and so forth. Moreover, spontaneously hypertensive rats (SHRs) were daily gavaged with LSE (60 mg/kg) for 10 weeks. LSE remarkably reduced systolic blood pressure (SBP). The hypertension-induced renal damage was improved by suppressing inflammation and oxidative stress, which was consistent with the prediction of network pharmacology. In addition, LSE treatment remarkably increased the relative abundances of and the production of short-chain fatty acids in the intestine. Our study indicated that a byproduct of litchi, namely, litchi seed, may be effective in reducing SBP and alleviating hypertensive renal damage.
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http://dx.doi.org/10.1021/acs.jafc.0c07046DOI Listing
February 2021

Dihydroartemisinin attenuates osteoarthritis by inhibiting abnormal bone remodeling and angiogenesis in subchondral bone.

Int J Mol Med 2021 03 15;47(3). Epub 2021 Jan 15.

Orthopedics Ward 3, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China.

The present study aimed to investigate whether dihydroartemisinin (DHA) alleviates osteoarthritis (OA) in a mouse model of OA. Ten‑week‑old female C57BL/6j mice were used to establish OA models by anterior cruciate ligament transection (ACLT) and ovariectomized (OVX). DHA was then used to treat the OA in the ACLT and OVX mice. Safranin O‑fast green staining and Osteoarthritis Research Society International (OARSI)‑modified Mankin scores were used to grade articular cartilage degeneration. Expression of metalloproteinase‑13 (MMP‑13) and vascular endothelial growth factor (VEGF) in the articular cartilage and leukemia inhibitory factor (LIF), sclerostin, and β‑catenin in the subchondral bone were analyzed by immunohistochemistry. Expression of RANKL and CD31 were detected by immunofluorescence. Micro‑computed tomography was used to ascertain alterations in the microarchitecture of the subchondral bone. The results demonstrated that DHA decreased MMP‑13 and VEGF expression in the articular cartilage. DHA decreased OARSI scores and reduced articular cartilage degeneration. In addition, DHA reduced abnormal subchondral bone remodeling, as demonstrated by a reduction in trabecular separation (Tb.Sp), increased bone volume fractions (BV/TV), as well as bone mineral densities (BMD) compared with the ACLT+vehicle group and the OVX+vehicle group. Furthermore, DHA decreased the inhibition of sclerostin through reduction of LIF secretion by osteoclasts and, hence, attenuated aberrant bone remodeling and inhibited angiogenesis in subchondral bone, further reducing the progression of OA. The present study demonstrated that DHA attenuated OA by inhibiting abnormal bone remodeling and angiogenesis in subchondral bone, which may be a potential therapeutic target for this disease.
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http://dx.doi.org/10.3892/ijmm.2021.4855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846423PMC
March 2021

Psychosocial impacts of post-disaster compensation processes: Community-wide avoidance behaviors.

Soc Sci Med 2021 02 23;270:113640. Epub 2020 Dec 23.

Department of Sociology, 431 Murray Hall, Oklahoma State University, Stillwater, OK, 74078, USA. Electronic address:

Rationale: There is a small but growing body of literature on litigation- and compensation-related stress after disasters. Results of these studies are consistent and unsurprising: compensation processes are a source of stress to plaintiffs and their families. "Litigation Response Syndrome"-anxiety, stress, and depression-is common among those exposed to the pressures of litigation (Lees-Haley 1988). However, little is known about how compensation processes-claims, litigation, and settlements-affect communities at large.

Objective: Building on prior research, we examine adverse impacts of compensation processes in Roane County, Tennessee five years following the Tennessee Valley Authority coal ash spill. We investigate whether compensation-related stress occurs at a community level, as well as avoidance behaviors as measured by the Impact of Event Scale.

Method: Based on data from a 2014 household mail survey of a random sample of 716 residents of Roane County, we examine the relationship between compensation processes and event-related avoidance behaviors.

Results: We found that compensation-related stress is not limited to those directly involved with compensation processes. Respondents view these processes as adversely impacting the community at large. The strongest contributors to event-related avoidance behaviors are beliefs about adverse compensation impacts and the effectiveness of cleanup and restoration activities, socioeconomic status, and economic resource loss. Therefore, it appears that Litigation Response Syndrome can extend to some members of the community who were not directly involved in litigation and compensation processes.
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http://dx.doi.org/10.1016/j.socscimed.2020.113640DOI Listing
February 2021

Phase II Study of Preoperative Intra-Arterial Epirubicin, Etoposide, and Oxaliplatin Combined with Oral S-1 Chemotherapy for the Treatment of Borrmann Type 4 Gastric Cancer.

J Gastric Cancer 2020 Dec 29;20(4):395-407. Epub 2020 Dec 29.

Jinling Hospital Research Institute of General Surgery, School of Medicine, Nanjing University, Nanjing, China.

Purpose: A phase II study was conducted to evaluate the safety and efficacy of preoperative, intra-arterial perfusion of epirubicin, etoposide, and oxaliplatin combined with oral chemotherapy S-1 (SEEOX) for the treatment of type 4 gastric cancer.

Materials And Methods: A single-center, single-arm phase II trial was conducted on 36 patients with histologically proven type 4 gastric cancer without distant peritoneal or organ metastasis. Patients received 3, 21-day courses of SEEOX preoperative chemotherapy. The primary endpoint was overall survival (OS) and the secondary outcomes assessed were chemotherapeutic response, radical resection rate, pathological regression, toxicities, postoperative morbidity, and mortality.

Results: All patients were at an advanced stage of cancer (stage III or IV) and completed the entire course of treatment. Based on changes in tumor volume and peritoneal metastasis, the objective response rate was 55.6% (20/36; 95% confidence interval [CI], 38.5%-72.6%) and the disease control rate was 69.4% (25/36; 95% CI, 53.6%-85.3%). The radical resection rate was 75% (27/36; 95% CI, 60.1%-89.9%) and the proportion of R0 resections was 66.7% (21/36; 95% CI, 50.5%-82.8%). The pathological response rate was 33.3%, of which 13.9% showed complete pathological regression. The median survival was 27.1 months (95% CI, 22.24-31.97 months), and the 2-year OS was 48.5% (95% CI, 30.86%-66.1%).

Conclusions: Preoperative SEEOX is a safe and effective treatment for type 4 gastric cancer. Based on these preliminary data, a phase III study will be conducted to confirm the superiority of this regimen over standard treatment.

Trial Registration: ClinicalTrials.gov Identifier: NCT02949258.
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http://dx.doi.org/10.5230/jgc.2020.20.e40DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781743PMC
December 2020