Publications by authors named "Lu Xu"

834 Publications

LncRNA-HEIH is a Novel Diagnostic and Predictive Biomarker in Gastric Cancer.

Genet Test Mol Biomarkers 2021 Apr;25(4):284-292

Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China.

Gastric cancer (GC) is associated with a high mortality rate. Long noncoding RNA (lncRNA)-high expressed in hepatocellular carcinoma (HEIH) has recently gained interest as a marker for the detection of several cancer types. This study was designed to uncover the function of lncRNA-HEIH in GC. Oncomine was used to analyze HEIH expression in cancerous and paired noncancerous tissues of GC patients. Subsequently, the expression levels of HEIH in GC cells was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, the effects of HEIH expression level on clinicopathological parameters and prognosis were further studied by statistical analysis and Kaplan-Meier survival curves. GC cell proliferation and the influence of HEIH on the sensitivity of cells to oxaliplatin following HEIH knockdown were assessed using sulforhodamine blue (SRB) assays in the MKN45 and AGS cell lines. In addition, the expression levels of p53 were detected by RT-qPCR following knockdown of HEIH. The lncRNA-HEIH was highly expressed in both GC tissues and GC cell lines. Patients with high HEIH expression were associated with medium-high differentiation ( = 0.0058), distant metastasis (M,  = 0.0378), lymph node metastasis (N,  = 0.0083), and a deeper tumor invasion (T,  = 0.0204). The elevated expression levels of HEIH in GC patients were associated with a worse prognosis compared to GC patients with low HEIH expression. This finding was supported by the parameters overall survival ( = 3.3e-06), first progression ( = 0.00028), and postprogression ( = 1.5e-08). Downregulation of HEIH expression inhibited cell proliferation, enhanced oxaliplatin sensitivity, and induced the expression of p53 in MKN45 and AGC cells. These findings provide evidence that HEIH may be useful as a prognostic biomarker in GC. This lncRNA may also serve as a potential therapeutic target in GC patients.
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http://dx.doi.org/10.1089/gtmb.2020.0270DOI Listing
April 2021

Effects of Allicin on Late Sodium Current Caused by ΔKPQ-SCN5A Mutation in HEK293 Cells.

Front Physiol 2021 29;12:636485. Epub 2021 Mar 29.

Department of Cardiology, Fujian Provincial Hospital, Provincial Clinical Medicine College of Fujian Medical University, Fuzhou, China.

Aim: The aim was to study the effect of Allitridum (Allicin) on the heterologous expression of the late sodium current on the ΔKPQ-SCN5A mutations in HEK293 cells, with a view to screening new drugs for the treatment of long QT syndrome type 3 (LQT3).

Methods And Results: The ΔKPQ-SCN5A plasmid was transiently transferred into HEK293 cells by liposome technology and administered by extracellular perfusion, and the sodium current was recorded by whole-cell patch-clamp technology. Application of Allicin 30 μM reduced the late sodium current ( ) of the Nav1.5 channel current encoded by ΔKPQ-SCN5A from 1.92 ± 0.12 to 0.65 ± 0.03 pA/pF ( < 0.01, = 15), which resulted in the decrease of / (from 0.94% ± 0.04% to 0.32% ± 0.02%). Furthermore, treatment with Allicin could move the steady-state inactivation of the channel to a more negative direction, resulting in an increase in channel inactivation at the same voltage, which reduced the increase in the window current and further increased the inactivation of the channel intermediate state. However, it had no effect on channel steady-state activation (SSA), inactivation mechanics, and recovery dynamics after inactivation. What's more, the Nav1.5 channel protein levels of membrane in the ΔKPQ-SCN5A mutation were enhanced from 0.49% ± 0.04% to 0.76% ± 0.02% with the effect of 30 mM Allicin, close to 0.89% ± 0.02% of the WT.

Conclusion: Allicin reduced the late sodium current of ΔKPQ-SCN5A, whose mechanism may be related to the increase of channel steady-state inactivation (SSI) and intermediate-state inactivation (ISI) by the drug, thus reducing the window current.
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http://dx.doi.org/10.3389/fphys.2021.636485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039306PMC
March 2021

Effect of disseminated intravascular coagulation on donation after citizens' death donor kidneys.

Transl Androl Urol 2021 Mar;10(3):1273-1278

Organ Transplantation Center of the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: To investigate the effect of disseminated intravascular coagulation (DIC) on donor kidney in donation after citizens' death (DCD) donors.

Methods: The clinical and laboratory data of 159 DCD donors obtained by our center in 2018 were retrospectively analyzed. The DIC diagnosis was performed according to the Chinese DIC scoring system (CDSS). The donors were divided into two groups: DIC (+) and DIC (-). The difference between kidney rejection rate and zero puncture glomerular microthrombus formation rate were compared.

Results: Among the 159 DCD donors, 11 were discarded (accounting for 6.91%). The reasons for the discarded cases included 5 cases (3.14%) for moderate and severe glomerular microthrombus formation in the renal zero puncture pathology; 2 cases (1.26%) for glomerular sclerosis ratio over 50%; 2 cases (1.26%) for long-term low blood pressure before pregnancy and significantly increased serum creatinine level and no urine; 1 case (0.73%) for kidney stones and stagnant water; 1 case (0.63%) for malignant tumor. The donor rejection rate of the DIC (+) group was higher than that of the DIC (-) group, and the difference was statistically significant (P<0.05). Among all donors, 10 cases (6.29%) were found to have glomerular microthrombus at zero puncture, and the microthrombotic rate in the DIC (+) group was significantly higher than that in the DIC (-) group (P<0.05). Of the 10 microthrombotic donors, 5 donors with severe glomerular microthrombus were discarded.

Conclusions: Donor-induced DIC can easily cause renal glomerular microthrombus formation, and the donor kidney rejection rate has increased.
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http://dx.doi.org/10.21037/tau-20-785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039612PMC
March 2021

Stimulated biodegradation of all alkanes in soil.

Chemosphere 2021 Apr 5;278:130444. Epub 2021 Apr 5.

School of Environmental and Municipal Engineering, Xi'an University of Architecture and Technology, 710055, Shaanxi, Xi'an, China; Key Laboratory of Northwest Water Resources, Environment and Ecology, MOE, China; Key Laboratory of Environmental Engineering, Shaanxi Province, China.

This study aim to investigate the biodegradation of all alkanes in soil by adding stimulater and indigenous bacteria. The experiments were carried out by adding native bacteria and the stimulater to the soil S1 (total petroleum hydrocarbon (TPH) = 22,745 mg/kg) and soil S2 (TPH = 13,833 mg/kg) to explored the effect and mechanism of the stimulated biodegradation of all alkanes in soil. The results showed that most alkanes were used as the main carbon source of TPH in the late stimulation stage, so that all alkanes could be biodegraded by stimulating. The biodegradation of C - C (4527 mg/kg) and C - C (8530 mg/kg) were much higher than the stimulated biodegradation of partial alkanes, which indicated that the biodegradation effect of TPH was greatly improved. In addition, for the stimulated biodegradation of all alkanes group, the relative activity of TPH (TPH biodegradation/DOC consumption) was nearly 5 times that of the stimulated biodegradation of partial alkanes group in the late stimulation stage. The amount of ammonia allocated to TPH in the late stimulation stage was nearly 10 times that of DOC, and the organic matter components changed greatly in the early stimulation stage, but there was basically no change in the later stage. It showed that the hydrocarbon degraders in the stimulated biodegradation of all alkanes group used DOC as the main carbon source in the early stimulation stage and mainly degrade TPH in the later stage, which improved the biodegradation efficiency of petroleum hydrocarbons.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130444DOI Listing
April 2021

Risk factors for brain metastases in patients with non-small cell lung cancer: a meta-analysis of 43 studies.

Ann Palliat Med 2021 Apr 1. Epub 2021 Apr 1.

School of Medicine, Southeast University, Nanjing, China; Department of Respiratory Medicine, Zhongda Hospital of Southeast University, Nanjing, China.

Background: Lung cancer is a leading cause of cancer-related mortality worldwide. The purpose of our meta-analysis was to assess the risk factors for brain metastases (BM) in patients with non-small cell lung cancer (NSCLC).

Methods: Multiple databases, including PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang, were systematically searched to recruit relevant studies investigating the risk factors for BM in NSCLC patients. The Newcastle-Ottawa Scale was used to evaluate literature quality, and the meta-analysis was performed using the Review Manager 5.3. Evidence quality evaluation was carried out according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) standard. The estimated odds ratio (OR) and 95% confidence intervals (CIs) were set as effect measures. Funnel plots and sensitivity analyses were used to assess publication bias and the robustness and reliability of the combined results, respectively.

Results: A total of 43 studies with 11,415 participants were included in this meta-analysis. The results indicated that the following factors were significantly associated with an increased risk of BM in NSCLC patients (P<0.05): (I) gender (female) (OR =1.32, 95% CI: 1.17-1.49, P<0.00001); (II) adenocarcinoma (OR =2.34, 95% CI: 1.76-3.11, P<0.00001) or non-squamous cell carcinoma (OR =0.63, 95% CI: 0.42-0.94, P=0.02); (III) advanced tumor stage (OR =1.48, 95% CI: 1.01-2.17, P=0.04); (IV) node stage (OR =2.19, 95% CI: 1.39-3.45, P=0.0007); (V) lymphatic metastasis (OR =2.43, 95% CI: 1.76-3.36, P<0.00001); (VI) epidermal growth factor receptor (EGFR) gene mutation (OR =1.88, 95% CI: 1.26-2.80, P=0.002); (VII) kirsten rat sarcoma viral oncogene (KRAS) gene mutation (OR =2.99, 95% CI: 1.82-4.91, P<0.00001); (VIII) higher levels of carcinoembryonic antigen (P<0.00001), carbohydrate antigen 199 (P<0.0001), cytokeratin-19 fragment (P=0.04), neuron-specific enolase (P<0.00001), and carbohydrate antigen 125 (P=0.0005).

Conclusions: This meta-analysis demonstrated that NSCLC patients with BM have more aggressive clinical features.
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http://dx.doi.org/10.21037/apm-20-1722DOI Listing
April 2021

Molecular-networking-guided discovery of species-specific markers for discriminating five medicinal Paris herbs.

Phytomedicine 2021 May 10;85:153542. Epub 2021 Mar 10.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing 210009, China. Electronic address:

Background: Paridis Rhizoma (PR) is a famous traditional herbal medicine. Apart from two officially recorded species, viz. Paris polyphylla Smith var. yunnanensis (Franch.) Hand. - Mazz. (PPY) and P. polyphylla Smith var. chinensis (Franch.) Hara (PPC), there are still many other species used as folk medicine. It is necessary to understand the metabolic differences among Paris species.

Purpose: To establish a strategy that can discover species-specific steroidal saponin markers to distinguish closely-related Paris herbs for quality and safety control.

Methods: A new strategy of molecular-networking-guided discovery of species-specific markers was proposed. Firstly, the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was applied to obtain the MS and MS/MS data of all samples. Then, molecular networking (MN) was created using MS/MS data to prescreen the steroidal saponins for subsequent analysis. Next, the principal component analysis (PCA) and orthogonal partial least square discriminant analysis (OPLS-DA) models were established to discover potential markers. Finally, the verification, identification and distribution of chemical markers were performed.

Results: A total of 126 steroidal saponins were screened out from five species using MN. Five species were classified successfully by OPLS-DA model, and 18 species-specific markers were discovered combining the variable importance in the projection (VIP) value, P value (one-way ANOVA) and their relative abundance. These markers could predict the species of Paris herbs correctly.

Conclusion: These results revealed that this new strategy could be an efficient way for chemical discrimination of medicinal herbs with close genetic relationship.
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http://dx.doi.org/10.1016/j.phymed.2021.153542DOI Listing
May 2021

Chronic lung inflammation and pulmonary fibrosis after multiple intranasal instillation of PM in mice.

Environ Toxicol 2021 Mar 29. Epub 2021 Mar 29.

Department of Pulmonary and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Fine particulate matter (PM ) is an important component of air pollution and can induce lung inflammation and oxidative stress. We hypothesized that PM could play a role in the induction of pulmonary fibrosis. We examined whether multiple intranasal instillation of PM can induce pulmonary fibrosis in the mouse, and also investigated the underlying pro-fibrotic signaling pathways. C57/BL6 mice were intranasally instilled with 50 μl of PM suspension (7.8 μg/g body weight) or PBS three times a week over 3 weeks, 6 weeks or 9 weeks. To observe the recovery of pulmonary fibrosis after the termination of PM exposure, 9 week-PM instilled mice were also studied at 3 weeks after termination of instillation. There were significant decreases in total lung capacity (TLC) and compliance (Cchord) in the 9-week PM -instilled mice, while there were increased histological fibrosis scores with enhanced type I collagen and hydroxyproline deposition, increased mitochondrial ROS levels and NOX activity, decreased total SOD and GSH levels, accompanied by decreased mitochondrial number and aberrant mitochondrial morphology (swelling, vacuolization, cristal disruption, reduced matrix density) in PM -instilled mice. Multiple PM instillation resulted in increased expression of TGFβ1, increases of N-Cadherin and Vimentin and a decrease of E-Cadherin. It also led to decreases in OPA1 and MFN2, and increases in Parkin, SQSTM1/p62, the ratio of light china (LC) 3B II to LC3B I, PI3k/Akt phosphorylation, and NLRP3 expression. Intranasal instillation of PM for 9 weeks induced lung inflammation and pulmonary fibrosis, which was linked with aberrant epithelial-mesenchymal transition, oxidative stress, mitochondrial damage and mitophagy, as well as activation of TGFβ1-PI3K/Akt, TGFβ1- NOX and TGFβ1-NLRP3 pathways.
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http://dx.doi.org/10.1002/tox.23140DOI Listing
March 2021

Case Report: Whole-Exome Sequencing With MLPA Revealed Variants in Two Genes in a Patient With Combined Manifestations of Spinal Muscular Atrophy and Duchenne Muscular Dystrophy.

Front Genet 2021 10;12:605611. Epub 2021 Mar 10.

National Clinical Research Center for Child Health, Department of Neurology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD) are two common kinds of neuromuscular disorders sharing various similarities in clinical manifestations. SMA is an autosomal recessive genetic disorder that results from biallelic mutations of the survival motor neuron 1 gene (; OMIM 600354) on the 5q13 chromosome. DMD is an X-linked disorder caused by defects in the gene (OMIM 300377) on the X chromosome. Here, for the first time, we report a case from a Chinese family who present with clinical manifestations of both two diseases, including poor motor development and progressive muscle weakness. We identified a homozygous deletion in exons 7 and 8 of the gene and a deletion in exon 50 of the gene by whole-exome sequencing (WES) and multiplex ligation-dependent probe amplification (MLPA). This case expands our understanding of diagnosis for synchronous SMA and DMD and highlights the importance of various genetic testing methods, including WES, in differential diagnosis of neuromuscular diseases.
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http://dx.doi.org/10.3389/fgene.2021.605611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987946PMC
March 2021

Effect of unplanned spontaneous follicular growth and ovulation on pregnancy outcomes in planned artificial frozen embryo transfer cycles: a propensity score matching study.

Hum Reprod 2021 Mar 25. Epub 2021 Mar 25.

Department of Reproductive Medicine, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.

Study Question: Does unplanned spontaneous follicular growth and ovulation affect clinical outcomes after planned artificial frozen-thawed embryo transfer (AC-FET) cycles?

Summary Answer: AC-FET and spontaneous follicular growth and ovulation events resulted in notably better pregnancy outcomes with a significantly higher implantation rate (IR), clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR) and live birth rate (LBR) and a significantly lower miscarriage rate.

What Is Known Already: The AC-FET protocol without GnRH agonist administration is associated with a low incidence of follicular growth and ovulation. In the literature, authors often refer to these types of cycles with concern due to possibly impaired FET outcomes. However, the real impact of such cycles has yet to be elucidated due to the lack of existing data.

Study Design, Size, Duration: This was a retrospective clinical study involving 2256 AC-FET cycles conducted between January 2017 and August 2019. Propensity score (PS) matching was used to control for confounding variables.

Participants/materials, Setting, Methods: Subjects were divided into two groups: a study group: cycles with spontaneous follicular growth and ovulation (the maximum diameter of follicles in any ovary was ≥14 mm and ovulation was confirmed by consecutive ultrasound examinations) and a control group featuring cycles without growing follicles (the maximum diameter of follicles in both ovaries were <10 mm). The study group was matched by PS with the control group at a ratio of 1:2. The study group consisted of 195 patients before PS matching and 176 patients after matching. The numbers of participants in the control group before and after PS matching were 2061 and 329, respectively.

Main Results And The Role Of Chance: This analysis showed that patient age (adjusted odds ratio [aOR] 1.05; 95% CI 1.01-1.09; P=0.010) and basal FSH level (aOR 1.06; 95% CI 1.01-1.11; P=0.012) were significantly and positively related with the spontaneous follicular growth and ovulation event. In addition, this event was negatively correlated with BMI (aOR 0.92; 95% CI 0.87-0.97; P=0.002), AMH level (aOR 0.66; 95% CI 0.59-0.74; P<0.001) and a high starting oestrogen dose (aOR 0.53; 95% CI 0.38-0.76 for 6 mg vs. 4 mg; P<0.001). Baseline characteristics were similar between groups after PS matching. Patients in the study group had a significantly higher IR (28.8% vs. 21.8%, P=0.016), CPR (44.9% vs. 33.4%, P=0.011), OPR (39.2% vs. 26.1%, P=0.002) and LBR (39.2% vs. 24.9%, P=0.001) and a lower miscarriage rate (12.7% vs. 25.5%, P=0.030), compared with those in the control group.

Limitations, Reasons For Caution: This was a retrospective study carried out in a single centre and was therefore susceptible to bias. In addition, we only analysed patients with normal ovulation patterns and excluded those with follicular growth but without ovulation. Further studies remain necessary to confirm our results.

Wider Implications Of The Findings: It is not necessary to cancel cycles that experience spontaneous follicular growth and ovulation. Our data support promising clinical outcomes after this event. Our findings are important as they can better inform clinicians and patients.

Study Funding/competing Interest(s): This research was supported by National Natural Science Foundation of China (grant no. 81701507, 81801404, 81871210, 82071648), Natural Science Foundation of Jiangsu Province (grant no. BK20171126, BK20201123) and Jiangsu Province '333' project. The authors declare that they have no competing interests.

Trial Registration Number: N/A.
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http://dx.doi.org/10.1093/humrep/deab059DOI Listing
March 2021

High Expression of CLEC11A Predicts Favorable Prognosis in Acute Myeloid Leukemia.

Front Oncol 2021 2;11:608932. Epub 2021 Mar 2.

Department of Hematology, Chinese People's Liberation Army General Hospital, Beijing, China.

Background: Acute myeloid leukemia (AML) is a heterogeneous disease of the hematopoietic system, for which identification of novel molecular markers is potentially important for clinical prognosis and is an urgent need for treatment optimization.

Methods: We selected C-type lectin domain family 11, member A (CLEC11A) for study several public databases, comparing expression among a variety of tumors and normal samples as well as different organs and tissues. To investigated the relationship between CLEC11A expression and clinical characteristics, we derived an AML cohort from The Cancer Genome Atlas (TCGA); we also investigated the Bloodspot and HemaExplorer databases. The Kaplan-Meier method and log-rank test were used to evaluate the associations between CLEC11A mRNA expression, as well as DNA methylation, and overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS). DNA methylation levels of CLEC11A from our own 28 AML patients were assessed and related to chemotherapeutic outcomes. Bioinformatics analysis of CLEC11A was carried out using public databases.

Results: Multiple public databases revealed that CLEC11A expression was higher in leukemia. The TCGA data revealed that high CLEC11A expression was linked with favorable prognosis (OS -value = 2e-04; EFS -value = 6e-04), which was validated in GSE6891 (OS -value = 0; EFS -value = 0; RFS -value = 2e-03). Methylation of CLEC11A was negatively associated with CLEC11A expression, and high CLEC11A methylation level group was linked to poorer prognosis (OS -value = 1e-02; EFS -value = 2e-02). Meanwhile, CLEC11A hypermethylation was associated with poor induction remission rate and dismal survival. Bioinformatic analysis also showed that CLEC11A was an up-regulated gene in leukemogenesis.

Conclusion: CLEC11A may be used as a prognostic biomarker, and could do benefit for AML patients by providing precise treatment indications, and its unique gene pattern should aid in further understanding the heterogeneous AML mechanisms.
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http://dx.doi.org/10.3389/fonc.2021.608932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966831PMC
March 2021

[Degradation of Dye Rhodamine B by Solar Thermally Activated Persulfate].

Huan Jing Ke Xue 2021 Mar;42(3):1451-1460

School of Environmental and Municipal Engineering, Xi'an University of Architecture and Technology, Xi'an 710055, China.

In advanced oxidation technology based on sulfate radicals, thermal activation is one of the most effective methods for persulfate (PS) activation, with broad application potential for the use of solar energy to activate PS to degrade pollutants. In this study, the efficiency and mechanism of degradation of rhodamine B by solar thermally activated PS were investigated using a solar collector reactor. The effects of solar irradiation intensity, PS concentration, substrate concentration, initial pH of the solution, and background water quality on the degradation efficiency of rhodamine B were examined. The results show that the solar thermally activated PS system has outstanding oxidation degradation performance with respect to organic pollutants. The removal rate and mineralization rate of rhodamine B reached 94% and 60%, respectively, after a 120 min reaction time. The treatment efficiency of the system was notably affected by the solar radiation intensity, with performance ranked in the order sunny days > cloudy days > rainy days. The treatment efficiency of the system could be significantly improved by increasing the concentration of PS or reducing the initial concentration of the substrate, and by adjusting the initial pH of the solution to neutral. SO·and·OH are the main active oxidants in the reaction system, and·OH plays a major role in the degradation process.
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http://dx.doi.org/10.13227/j.hjkx.202007187DOI Listing
March 2021

Inhibition of Smad3 in macrophages promotes Aβ efflux from the brain and thereby ameliorates Alzheimer's pathology.

Brain Behav Immun 2021 Mar 15. Epub 2021 Mar 15.

School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China; The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing 211166, China; Department of Neurology, Sir Run Run Hospital, Nanjing Medical University, Nanjing 211166, China. Electronic address:

Impaired amyloid-β (Aβ) clearance is believed to be a primary cause of Alzheimer's disease (AD), and peripheral abnormalities in Aβ clearance have recently been linked to AD pathogenesis and progression. Data from recent genome-wide association studies have linked genetic risk factors associated with altered functions of more immune cells to AD pathology. Here, we first identified correlations of Smad3 signaling activation in peripheral macrophages with AD progression and phagocytosis of Aβ. Then, manipulating the Smad3 signaling regulated macrophage phagocytosis of Aβ and induced switch of macrophage inflammatory phenotypes in our cell cultures. In our mouse models, flag-tagged or fluorescent-dye conjugated Aβ was injected into the lateral ventricles or tail veins, and traced. Interestingly, blocking Smad3 signaling efficiently increased Aβ clearance by macrophages, reduced Aβ in the periphery and thereby enhanced Aβ efflux from the brain. Moreover, in our APP/PS1 transgenic AD model mice, Smad3 inhibition significantly attenuated Aβ deposition and neuroinflammation, and ameliorated cognitive deficits, probably by enhancing the peripheral clearance of Aβ. In conclusion, enhancing Aβ clearance by peripheral macrophages through Smad3 inhibition attenuated AD-related pathology and cognitive deficits, which may provide a new perspective for understanding AD and finding novel therapeutic approaches.
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http://dx.doi.org/10.1016/j.bbi.2021.03.013DOI Listing
March 2021

Prevalence of extramammary Paget's disease in urban China: a population-based study.

Orphanet J Rare Dis 2021 Mar 17;16(1):134. Epub 2021 Mar 17.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.

Background: Extramammary Paget's disease (EMPD) is an intraepithelial adenocarcinoma. The chronic relapsing clinical course and unbearable clinical symptoms of extramammary Paget's disease usually result in a markedly diminished quality of life. No national data are available on descriptive epidemiology of EMPD in China, the most populous country over the world. This population-based study aimed to estimate the prevalence and associated sex and age patterns of EMPD in China.

Methods: This study was conducted using data from China's Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance, covering approximately 0.43 billion Chinese urban residents in 2016. Patients with EMPD were identified based on the diagnostic names and codes in claim data.

Results: A total of 53 males and 31 females with EMPD were found. The crude prevalence in 2016 was 0.04 per 100,000 population [95% confidence interval (CI) 0.02-0.06], ranging from 0.01 (95% CI 0.00-0.02) in North or Northeast China to 0.08 (95% CI 0.03-0.16) in Southwest China. The rate was higher in males (0.05, 95% CI 0.03-0.08) compared with females (0.03, 95% CI 0.02-0.05). The mean age of patients was 65.87 (standard deviation: 14.21) years, with the peak prevalence appeared in patients aged 70-79 (0.28, 95% CI 0.16-0.42).

Conclusions: The prevalence of EMPD was markedly lower than those in the United States and Europe, and varied across regions in China. Chinese patients were much younger, with significant male predominance. Further studies are warranted to examine potential pathophysiologic mechanism.
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http://dx.doi.org/10.1186/s13023-021-01715-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972239PMC
March 2021

Mitochondrial DNA enables AIM2 inflammasome activation and hepatocyte pyroptosis in non-alcoholic fatty liver disease.

Am J Physiol Gastrointest Liver Physiol 2021 Mar 17. Epub 2021 Mar 17.

Department of Oncology, Xuzhou City Cancer Hospital, China.

Nonalcoholic fatty liver disease (NAFLD) is typified by accumulating excess liver triacylglycerol, inflammation, and liver dysfunction. This study was aimed to investigate the role of mitochondrial DNA synthesis-induced activation of Absent in melanoma 2 (AIM2) inflammasome and pyroptosis in NAFLD. Mice were raised on a high-fat diet for 24 weeks to establish NAFLD models. F4/80 immunofluorescence was performed to reflect the inflammatory response in the liver of mice. Western blot, ELISA, and immunofluorescence were adopted to determine the expression of AIM2 inflammasome-related proteins and factors. EdU immunofluorescence was applied for the examination of mitochondrial DNA expression and flow cytometry for cell pyroptosis. Agarose gel electrophoresis was used to detect the integrity of extracted mouse mitochondrial DNA (mtDNA). The levels of AIM2 inflammasome-related proteins in the liver and the levels of IL-1β and IL-18 in serum were elevated in high-fat diet-induced NAFLD mice. AIM2 inflammasome activation and pyroptosis were triggered, and suppressed activation of AIM2 inflammasome alleviated the inflammation and pyroptosis in the liver of NAFLD mice. Mitochondria were severely damaged and mtDNA was synthesized after NAFLD modeling. Further, mtDNA treatment could promote palmitate (PA)-induced activation of AIM2 inflammasome and pyroptosis. Moreover, inhibition of IRF1 gene alleviated PA-induced AIM2 inflammasome activation and pyroptosis. In conclusion, mitochondrial DNA synthesis could enable AIM2 inflammasome activation and induce the hepatocyte pyroptosis, thereby exacerbating NAFLD.
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http://dx.doi.org/10.1152/ajpgi.00431.2020DOI Listing
March 2021

Electrocatalytic Reduction of N Using Metal-Doped Borophene.

ACS Appl Mater Interfaces 2021 Mar 17;13(12):14091-14101. Epub 2021 Mar 17.

School of Physics and Astronomy, University of Minnesota, 116 Church Street SE, Minneapolis, Minnesota 55455, United States.

Ammonia synthesis is an essential process in chemistry and industry. However, it is limited by the lack of efficient catalysts and high energy costs. Developing highly efficient systems for ammonia synthesis is an important and long-standing challenge. In this paper, a large class of metal atoms (including 3d/4d transition metals and main group metals) anchored onto borophene have been studied as single atom catalysts for ammonia synthesis. After comprehensive computational screening and systematic evaluation, four candidates stand out. We predict that Mo, Mn, Tc, and Cr@BM-β will have superior performance for catalytic reduction of N to NH with low limiting potentials of -0.26, -0.32, -0.38, and -0.48 V, respectively. Furthermore, we studied the activity of the competitive HER on M@BM-β. The results implied that the two materials Mo@BM-β and Mn@BM-β showed HER suppression. These properties exceed most currently reported nitrogen reduction reaction electrocatalysts. Our results suggest the possibility of efficient electrochemical reduction of N to NH in a lower energy process.
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http://dx.doi.org/10.1021/acsami.0c20553DOI Listing
March 2021

FEN1 is a prognostic biomarker for ER+ breast cancer and associated with tamoxifen resistance through the ERα/cyclin D1/Rb axis.

Ann Transl Med 2021 Feb;9(3):258

Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China.

Background: Tamoxifen is an important choice in endocrine therapy for patients with oestrogen receptor-positive (ER+) breast cancer, and disease progression-associated resistance to tamoxifen therapy is still challenging. Flap endonuclease-1 (FEN1) is used as a prognostic biomarker and is considered to participate in proliferation, migration, and drug resistance in multiple cancers, especially breast cancer, but the prognostic function of FEN1 in ER+ breast cancer, and whether FEN1 is related to tamoxifen resistance or not, remain to be explored.

Methods: On-line database Kaplan-Meier (KM) plotter, GEO datasets, and immunohistochemistry were used to analyse the prognostic value of FEN1 in ER+ breast cancer from mRNA and protein levels. Cell viability assay and colony formation assays showed the response of tamoxifen in MCF-7 and T47D cells. Microarray data with FEN1 siRNA control group in MCF-7 cells were analysed by Gene Set Enrichment Analysis (GSEA). The protein levels downstream of FEN1 were detected by western blot assay.

Results: ER+ breast cancer patients who received tamoxifen for adjuvant endocrine therapy with poor prognosis showed a high expression of FEN1. MCF-7 and T47D appeared resistant to tamoxifen after FEN1 over-expression and increased sensitivity to tamoxifen after FEN1 knockdown. Importantly, FEN1 over-expression could activate tamoxifen resistance through the ERα/cyclin D1/Rb axis.

Conclusions: As a biomarker of tamoxifen effectiveness, FEN1 participates in tamoxifen resistance through ERα/cyclin D1/Rb axis. In the future, reversing tamoxifen resistance by knocking-down FEN1 or by way of action as a small molecular inhibitor of FEN1 warrants further investigation.
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http://dx.doi.org/10.21037/atm-20-3068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940940PMC
February 2021

Prognostic models for amyotrophic lateral sclerosis: a systematic review.

J Neurol 2021 Mar 10. Epub 2021 Mar 10.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.

Background: Increasing prognostic models for amyotrophic lateral sclerosis (ALS) have been developed. However, no comprehensive evaluation of these models has been done. The purpose of this study was to map the prognostic models for ALS to assess their potential contribution and suggest future improvements on modeling strategy.

Methods: Databases including Medline, Embase, Web of Science, and Cochrane library were searched from inception to 20 February 2021. All studies developing and/or validating prognostic models for ALS were selected. Information regarding modelling method and methodological quality was extracted.

Results: A total of 28 studies describing the development of 34 models and the external validation of 19 models were included. The outcomes concerned were ALS progression (n = 12; 35%), change in weight (n = 1; 3%), respiratory insufficiency (n = 2; 6%), and survival (n = 19; 56%). Among the models predicting ALS progression or survival, the most frequently used predictors were age, ALS Functional Rating Scale/ALS Functional Rating Scale-Revised, site of onset, and disease duration. The modelling method adopted most was machine learning (n = 16; 47%). Most of the models (n = 25; 74%) were not presented. Discrimination and calibration were assessed in 12 (35%) and 2 (6%) models, respectively. Only one model by Westeneng et al. (Lancet Neurol 17:423-433, 2018) was assessed with overall low risk of bias and it performed well in both discrimination and calibration, suggesting a relatively reliable model for practice.

Conclusions: This study systematically reviewed the prognostic models for ALS. Their usefulness is questionable due to several methodological pitfalls and the lack of external validation done by fully independent researchers. Future research should pay more attention to the addition of novel promising predictors, external validation, and head-to-head comparisons of existing models.
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http://dx.doi.org/10.1007/s00415-021-10508-7DOI Listing
March 2021

Comparison of 1L Adjuvant Auxiliary Preparations with 2L Solely Polyethylene Glycol plus Ascorbic Acid Regime for Bowel Cleaning: A Meta-analysis of Randomized, Controlled Trials.

Biomed Res Int 2021 18;2021:6638858. Epub 2021 Feb 18.

Department of Gastroenterology, Ningbo First Hospital, Zhejiang, China.

The effectiveness of additional usage of adjuvants for bowel preparation is still unclear. This study compared 1L polyethylene glycol plus ascorbic acid with adjuvant drug regimens (1L PEG-AA, lower volume) with 2L polyethylene glycol plus ascorbic acid (2L PEG-A, low volume) to evaluate whether the adjuvants can be used to reduce the standard dosage of purgative further. The PubMed/MEDLINE, EMBASE, Cochrane Library, and Web of Science database were searched for randomized controlled trials (RCTs). The primary outcome was the efficacy of bowel preparation, and the secondary outcomes were patients' tolerability and complication rate. The overall quality of evidence was assessed using the GRADEpro guideline development tool. Five RCTs with a total of 1013 patients from Korea were included. The majority of patients were outpatients from different hospitals. The pooled data showed no significant difference in the adequate bowel preparation rate (89.3% versus 89.4%, RR 1, 95% CI 0.95-1.05, = 47%) as well as in the complication rate (RR for nausea 1.22, 95% CI 0.89-1.65, = 49%; RR for bloating 0.96, 95% CI 0.73-1.28, = 0%; RR for vomiting 0.69, 95% CI 0.32-1.50, = 33%; RR for abdominal pain 1.01, 95% CI 0.61-1.69, = 0%). But a significantly higher willingness rate was observed in the lower volume (85.1% versus 67.9%, RR 1.25, 95% CI 1.14-1.38, = 46%). The quality of primary outcome evidence was moderate. The findings of this meta-analysis revealed that 1L PEG-AA may be a viable alternative to 2L PEG-A, with comparable effectiveness, better patient preference, and no statistically significant adverse event occurrence.
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http://dx.doi.org/10.1155/2021/6638858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910058PMC
February 2021

Spin-Coupled Generalized Valence Bond Theory: New Perspectves on the Electronic Structure of Molecules and Chemical Bonds.

J Phys Chem A 2021 Mar 6;125(10):2021-2050. Epub 2021 Mar 6.

Department of Chemistry, University of York, York, YO10 5DD, U.K.

Spin-Coupled Generalized Valence Bond (SCGVB) theory provides the foundation for a comprehensive theory of the electronic structure of molecules. SCGVB theory offers a compelling orbital description of the electronic structure of molecules as well as an efficient and effective zero-order wave function for calculations striving for quantitative predictions of molecular structures, energetics, and other properties. The orbitals in the SCGVB wave function are usually semilocalized, and for most molecules, they can be interpreted using concepts familiar to all chemists (hybrid orbitals, localized bond pairs, lone pairs, etc.). SCGVB theory also provides new perspectives on the nature of the bonds in molecules such as C, Be and SF/SF. SCGVB theory contributes unparalleled insights into the underlying cause of the first-row anomaly in inorganic chemistry as well as the electronic structure of organic molecules and the electronic mechanisms of organic reactions. The SCGVB wave function accounts for nondynamical correlation effects and, thus, corrects the most serious deficiency in molecular orbital (RHF) wave functions. Dynamical correlation effects, which are critical for quantitative predictions, can be taken into account using the SCGVB wave function as the zero-order wave function for multireference configuration interaction or coupled cluster calculations.
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http://dx.doi.org/10.1021/acs.jpca.0c10472DOI Listing
March 2021

[Curcumin mediates IL-6/STAT3 signaling pathway to repair intestinal mucosal injury induced by 5-FU chemotherapy for colon cancer].

Zhongguo Zhong Yao Za Zhi 2021 Feb;46(3):670-677

Cancer Hospital of University of Chinese Academy of Sciences(Zhejiang Cancer Hospital) Hangzhou 310022, China.

This study aims to investigate the potential mechanism of curcumin in mediating interleukin-6(IL-6)/signal transducer and activator of transcription 3(STAT3) signaling pathway to repair intestinal mucosal injury induced by 5-fluorouracil(5-FU) chemotherapy for colon cancer. SD rats were intraperitoneally injected with 60 mg·kg~(-1)·d~(-1) 5-FU for 4 days to establish a model of intestinal mucosal injury. Then the rats were randomly divided into model group(equal volume of normal saline), curcumin low, medium and high dose groups(50, 100, 200 mg·kg~(-1)), and normal SD rats were used as control group(equal volume of normal saline). Each group received gavage administration for 4 consecutive days, and the changes of body weight and feces were recorded every day. After administration, blood was collected from the heart, and jejunum tissues were collected. The levels of serum interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) were detected by ELISA, and at the same time, the concentration of Evans blue(EB) in jejunum was measured. Hematoxylin-eosin(HE) staining was used to observe the pathological state of jejunum, and the length of jejunum villi and the depth of crypt were measured. The positive expression levels of claudin, occludin and ZO-1 were detected by immunohistochemistry. Western blot was used to detect the protein expression of IL-6, p-STAT3, E-cadherin, vimentin and N-cadherin in jejunum tissues. The results showed that, curcumin significantly increased body weight and fecal weight(P<0.05 or P<0.01), decreased fecal score, EB concentration, IL-1β and TNF-α levels(P<0.05 or P<0.01) in rats. In addition, curcumin maintained the integrity of mucosal surface and villi structure of jejunum to a large extent, and reduced pathological changes in a dose-dependent manner. Meanwhile, curcumin could increase the positive expression of occludin, claudin and ZO-1(P<0.05 or P<0.01), repair intestinal barrier function, downregulate the protein expression of IL-6, p-STAT3, vimentin and N-cadherin in jejunum tissues(P<0.05 or P<0.01), and upregulate the protein expression of E-cadherin(P<0.05). Therefore, curcumin could repair the intestinal mucosal injury induced by 5-FU chemotherapy for colon cancer, and the mechanism may be related to the inhibition of IL-6/STAT3 signal and the inhibition of epithelial-mesenchymal transition(EMT) process.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201106.401DOI Listing
February 2021

Taohuajing reduces oxidative stress and inflammation in diabetic cardiomyopathy through the sirtuin 1/nucleotide-binding oligomerization domain-like receptor protein 3 pathway.

BMC Complement Med Ther 2021 Feb 26;21(1):78. Epub 2021 Feb 26.

Department of Chinese Materia Medica and Natural Medicines, School of Pharmacy, the Air Force Medical University, 169 Changle West Road, Xi'an, 710032, Shanxi, China.

Background: Oxidative stress and inflammation promote the development of diabetic cardiomyopathy (DCM). Therefore, inhibiting these processes may show beneficial effects in the treatment of patients with DCM. Taohuajing (THJ) is prepared using Persicae semen (Taoren), Polygonatum sibiricum (Huangjing), and Carthami flos (Honghua) and may have applications in the treatment of DCM. However, the protective effects of THJ have not been thoroughly assessed. Accordingly, in this study, we aimed to investigate the protective effects of THJ in a model of DCM and further clarify the potential mechanisms.

Methods: A type 2 diabetes mellitus model was generated using male C57BL/6 mice. Echocardiography and histopathology were used to evaluate cardiac function. The expression levels of cytokines were measured using enzyme-linked immunosorbent assays. Western blotting and small interfering RNA were used to evaluate the targets of THJ.

Results: Compared with the control group, DCM mice showed cardiac dysfunction, metabolic disorder, fibrosis, and disorganized ultrastructure, and THJ treatment significantly inhibited these changes significantly. THJ treatment also inhibited the production of reactive oxygen species (ROS) and malondialdehyde (MDA), induced the production of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), decreased the levels of pro-inflammatory cytokines, and suppressed the activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome. These protective effects were abolished by sirtinol, an inhibitor of sirtuin1 (SIRT1).

Conclusions: Overall, THJ protected the heart from hyperglycemia-induced oxidative stress and inflammation in DCM mice via a mechanism involving SIRT1-mediated antioxidant proteins and suppression of the NLRP3 inflammasome.
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http://dx.doi.org/10.1186/s12906-021-03218-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913206PMC
February 2021

Trends and Patterns in Traditional Chinese Medicine Use Among Chinese Population in Late Adulthood: An Eight-Year Repeated Panel Survey.

Am J Chin Med 2021 20;49(2):269-283. Epub 2021 Feb 20.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, P. R. China.

Traditional Chinese medicine (TCM), originated from China, is different from Western medicine in theory and practice. This study aimed to document the longitudinal trends and the patterns by demographical characteristics in the prevalence of TCM among the middle-aged and elderly Chinese population. This study used nationally representative longitudinal survey data from the China Health and Retirement Longitudinal Study (CHARLS), covering approximately 20,000 individuals in each panel survey from 2011 to 2018. The questions regarding medication use in the questionnaire was used to identify the TCM users. The prevalence of using TCM for treating chronic diseases among the patients with chronic diseases stabilized between 2011 and 2018, while the prevalence of TCM use for any purpose among the overall population climbed from 19.03% (95% CI 18.37% to 19.69%) in 2011 to 23.91% (95% CI 23.23% to 24.60%) in 2015. Moreover, the prevalence of TCM use for nonchronic conditions among the overall population increased during the same period as well. The TCM users were more likely to be females and city dwellers. The increasing prevalence of TCM use for any purpose among the overall population reflects the increasing influence and potentials of TCM by year. With the expected rising demand in TCM for the following decades in China, more clinical trials on safety and healthcare policy regarding TCM are merited in the future.
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http://dx.doi.org/10.1142/S0192415X21500142DOI Listing
February 2021

Heterologous viral suppressor of RNA silencing breaks protein-based viral immunity in mixed viral infection.

Authors:
Xu Lu Feng Li

Sci China Life Sci 2021 Feb 9. Epub 2021 Feb 9.

Key laboratory of Horticultural Plant Biology (MOE), College of Horticulture and Forestry Sciences, Huazhong Agricultural University, Wuhan, 430070, China.

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http://dx.doi.org/10.1007/s11427-020-1873-1DOI Listing
February 2021

Comparative efficacy of pharmacological treatments on measures of self-rated functional outcomes using the Sheehan Disability Scale in patients with major depressive disorder: a systematic review and network meta-analysis.

CNS Spectr 2021 Feb 15:1-9. Epub 2021 Feb 15.

Mood Disorders Psychopharmacology Unit, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.

Objective: More than 50% patients with major depressive disorder (MDD) have severe functional impairment. The restoration of patient functioning is a critical therapeutic goal among patients with MDD. We conducted a systematic review and network meta-analysis to evaluate the efficacy of pharmacological treatments on self-rated functional outcomes using the Sheehan Disability Scale in adults with MDD in randomized clinical trials.

Methods: PubMed, EMBASE, PsycINFO, Cochrane Library, and ClinicalTrials.gov were searched from inception to December 10, 2019. Summary statistics are reported as weighted mean differences with 95% confidence intervals. Interventions were ranked using the surface under the cumulative ranking probabilities.

Results: We included 42 randomized controlled trials (RCTs) (n = 18 998) evaluating the efficacy of 13 different pharmacological treatments on functional outcomes, as measured by the Sheehan Disability Scale (SDS). Duloxetine was the most effective pharmacological agent on functional outcomes, followed by (ranked by efficacy): paroxetine, levomilnacipran, venlafaxine, quetiapine, desvenlafaxine, agomelatine, escitalopram, amitriptyline, bupropion, sertraline, vortioxetine, and fluoxetine. Serotonin and norepinephrine reuptake inhibitors were more effective than other drug classes. Additionally, the comparison-adjusted funnel plot suggested the publication bias between small and large studies was relatively low.

Conclusions: Our results indicate that there may be differences across antidepressant agents and classes with respect to self-reported functional outcomes. Validation and replication of these findings in large-scale RCTs are warranted. Our research results will be clinically useful for guiding psychiatrists in treating patients with MDD and functional impairment. PROSPERO registration number CRD42018116663.
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http://dx.doi.org/10.1017/S1092852921000171DOI Listing
February 2021

Association of uncoupling protein-2 -866G/A and Ala55Val polymorphisms with susceptibility to type 2 diabetes mellitus: A meta-analysis of case-control studies.

Medicine (Baltimore) 2021 Feb;100(6):e24464

School of Traditional Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine.

Background: Recently, the relationships between uncoupling protein-2 (UCP2) -866G/A (rs659366) and Ala55Val (rs660339) polymorphisms and the risk of type 2 diabetes mellitus (T2DM) have been explored considerably, but the results are greatly inconsistent. This meta-analysis was performed to further identify the association of UCP2 rs659366 and rs660339 with the risk of T2DM.

Methods: Eligible studies were searched from PubMed, Embase, Cochrane Library, VIP database, Chinese National Knowledge Infrastructure, and Chinese WanFang database until March 8, 2020. The odds ratios with corresponding 95% confidence intervals (CIs), and P-values were used to assess the strength of the association.

Results: A total of 26 studies were included in this study. UCP2 rs659366 was associated with the risk of T2DM in allele model (OR: 1.112, 95%CI: 1.009-1.224, P = 0.032), dominant model (OR: 1.189, 95%CI: 1.035-1.366, P = 0.014), and heterozygous model (OR: 1.177, 95%CI: 1.032-1.342, P = .015). A significantly increased risk of T2DM was detected in Asians by UCP2 rs659366 allele (OR: 1.132, 95%CI: 1.016-1.262, P = .025), dominant (OR: 1.218, 95%CI: 1.046-1.418, P = .011), homozygous (OR: 1.254, 95%CI: 1.022-1.540, P = .031) or heterozygous (OR: 1.198, 95%CI: 1.047-1.371, P = .009) models. There was no significant correlation between UCP2 rs660339 and the risk of T2DM (P>.05).

Conclusions: The UCP2 rs65366 is significantly associated with the risk of T2DM, especially in Asian population, while no evidence is found between the UCP2 rs660339 and the susceptibility to T2DM.
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http://dx.doi.org/10.1097/MD.0000000000024464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886456PMC
February 2021

Mitochondrial tRNA Mutation and Regulation of the Adiponectin Pathway in Maternally Inherited Hypertension in Chinese Han.

Front Cell Dev Biol 2020 22;8:623450. Epub 2021 Jan 22.

Department of Cardiology, The Sixth Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.

Some essential hypertension (EH) patients show maternal inheritance, which is the mode of mitochondrial DNA inheritance. This study examines the mechanisms by which mitochondrial mutations cause EH characterized by maternal inheritance. The study enrolled 115 volunteers, who were divided into maternally inherited EH (group A, = 17), non-maternally inherited EH (group B, = 65), and normal control (group C, = 33) groups. A mitochondrial tRNA (15910 C>T) gene mutation was significantly correlated with EH and may play an important role in the pathogenesis of maternally inherited EH. Examining two families carrying the mitochondrial tRNA 15910 C>T mutation, which disrupted base pairing and may affect the stability and function of mitochondrial tRNA, we find that the overall incidence of EH was 59.3% in the maternal family members and 90% in males, significantly higher than in the general population in China (23.2%), and that the EH began at a younger age in those carrying mitochondrial tRNA 15910 C>T. To reveal the mechanism through which mitochondrial tRNA 15910 C>T causes maternally inherited EH, we cultured human peripheral blood mononuclear cells from family A2 . We find that cells carrying mitochondrial tRNA 15910 C>T were more viable and proliferative, and the increased ATP production resulted in raised intracellular reactive oxygen species (ROS). Moreover, the mitochondrial dysfunction resulted in reduced APN levels, causing hypoadiponectinemia, which promoted cell proliferation, and produced more ROS. This vicious cycle promoted the occurrence of EH with maternally inherited mitochondrial tRNA 15910 C>T. The mitochondrial tRNA 15910 C>T mutation may induce hypertension by changing the APN, AdipoR1, PGC-1α, and ERRα signaling pathways to elevate blood pressure. We discover a new mitochondrial mutation (tRNA 15910 C>T) related to EH, reveal part of the mechanism by which mitochondrial mutations lead to the occurrence and development of maternally inherited EH, and discuss the role of APN in it.
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http://dx.doi.org/10.3389/fcell.2020.623450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862570PMC
January 2021

Urban prevalence of multiple sclerosis in China: A population-based study in six provinces.

Eur J Neurol 2021 May 23;28(5):1636-1644. Epub 2021 Feb 23.

Department of Neurology, Peking University Third Hospital, Beijing, China.

Background And Purpose: Multiple sclerosis (MS) is a rare neurological disease addressed by only few epidemiological studies in China. This population-based study aimed to estimate the prevalence of MS in China by using national medical insurance databases.

Methods: Data from the Urban Employee Basic Medical Insurance database and the Urban Residence Basic Medical Insurance database, which were collected during 2012 to 2016 and included approximately 0.20 billion residents in six provinces, were used in this population-based study. The prevalent patients with MS were identified via diagnostic text or disease codes.

Results: The crude prevalence in 2016 was 2.44 per 100,000 population (95% confidence interval (CI) 2.18-2.72), with the prevalence in females being higher than that in males. The standardized prevalence (based on 2010 Chinese census data) was 2.29 (95% CI 2.21-2.38). The prevalence in both sexes in 2016 increased up to the age range of 30-34 years. Subsequently, the female prevalence declined with increasing age, but male prevalence stabilized with increasing age. During the 5-year time period, prevalence ranged from 2.32 (95% CI 2.06-2.60) in 2015 to 2.91 (95% CI 2.39-3.47) in 2012.

Conclusions: The prevalence of MS in China was lower than that in Europe and North America. The temporal trend of prevalence in China was also observed to be stable. As the first prevalence study of MS in mainland China, this population-based study can provide useful information for worldwide healthcare services and prevention of MS.
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http://dx.doi.org/10.1111/ene.14764DOI Listing
May 2021

Circulating serum exosomal as a novel biomarker for early diagnosis of gastric cancer.

Future Oncol 2021 Mar 3;17(8):907-919. Epub 2021 Feb 3.

Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, China.

Gastric cancer (GC) is one of the common malignant tumors with high mortality. The abundance of miRNAs in serum exosomes has proved to have a high application value as a new noninvasive diagnostic method. The purpose of this study was to investigate whether serum exosomal could be used as a new biomarker for early diagnosis of GC and evaluate its clinical application value by detecting the expression of serum exosomal in 131 patients with primary GC and 122 healthy controls by real-time quantitative (qRT)-PCR. The results showed that the expression level of serum exosomal in GC patients was significantly lower than that in normal controls (p < 0.0001). In addition, the level was closely correlated with lymph node metastasis and tumor node metastasis stage of GC patients. The area under the curve for serum exosomal was 0.829, significantly higher than for other indicators. Furthermore, combined detection of serum exosomal , CEA and CA19-9 was more sensitive than any of the three alone or any pair. These results showed that serum exosomal could be used as a novel new tumor biomarker to improve diagnostic efficiency in GC.
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http://dx.doi.org/10.2217/fon-2020-0792DOI Listing
March 2021

Pembrolizumab Plus Ipilimumab or Placebo for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50%: Randomized, Double-Blind Phase III KEYNOTE-598 Study.

J Clin Oncol 2021 Jan 29:JCO2003579. Epub 2021 Jan 29.

LungenClinic, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany.

Purpose: Pembrolizumab monotherapy is standard first-line therapy for metastatic non-small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) ≥ 50% without actionable driver mutations. It is not known whether adding ipilimumab to pembrolizumab improves efficacy over pembrolizumab alone in this population.

Methods: In the randomized, double-blind, phase III KEYNOTE-598 trial (ClinicalTrials.gov identifier: NCT03302234), eligible patients with previously untreated metastatic NSCLC with PD-L1 TPS ≥ 50% and no sensitizing or aberrations were randomly allocated 1:1 to ipilimumab 1 mg/kg or placebo every 6 weeks for up to 18 doses; all participants received pembrolizumab 200 mg every 3 weeks for up to 35 doses. Primary end points were overall survival and progression-free survival.

Results: Of the 568 participants, 284 were randomly allocated to each group. Median overall survival was 21.4 months for pembrolizumab-ipilimumab versus 21.9 months for pembrolizumab-placebo (hazard ratio, 1.08; 95% CI, 0.85 to 1.37; = .74). Median progression-free survival was 8.2 months for pembrolizumab-ipilimumab versus 8.4 months for pembrolizumab-placebo (hazard ratio, 1.06; 95% CI, 0.86 to 1.30; = .72). Grade 3-5 adverse events occurred in 62.4% of pembrolizumab-ipilimumab recipients versus 50.2% of pembrolizumab-placebo recipients and led to death in 13.1% versus 7.5%. The external data and safety monitoring committee recommended that the study be stopped for futility and that participants discontinue ipilimumab and placebo.

Conclusion: Adding ipilimumab to pembrolizumab does not improve efficacy and is associated with greater toxicity than pembrolizumab monotherapy as first-line treatment for metastatic NSCLC with PD-L1 TPS ≥ 50% and no targetable or aberrations. These data do not support use of pembrolizumab-ipilimumab in place of pembrolizumab monotherapy in this population.
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http://dx.doi.org/10.1200/JCO.20.03579DOI Listing
January 2021

Associations between Inflammatory Cytokine Gene Polymorphisms and Susceptibilities to Intracranial Aneurysm in Chinese Population.

Biomed Res Int 2021 16;2021:8865601. Epub 2021 Jan 16.

Department of Epidemiology and Health Statistics, XiangYa School of Public Health, Central South University, Changsha, China.

Intracranial aneurysm (IA) is a complex disease caused by genetic and environmental factors. Evidence indicates that inflammation plays an important role in IA occurrence. We aimed to explore the associations between inflammatory cytokine gene polymorphisms and IA in a Chinese population. This study enrolled 768 participants of Han ethnicity, including 384 patients with IA and 384 healthy individuals. Sixteen single nucleotide polymorphisms (SNPs) of , , , and genes were genotyped using the Sequenom MassARRAY platform. Univariate and multivariate logistic regression analyses were used to analyze the associations. We found rs3181216 was significantly associated with IA in the recessive and additive models (OR = 0.46, 95% CI = 0.23-0.89, = 0.022; OR = 0.74, 95% CI = 0.56-0.98, = 0.034, respectively). rs1799964 was associated with IA in dominant and additive models (OR = 0.67, 95% CI = 0.46-0.98, = 0.041; OR = 0.71, 95% CI = 0.51-0.98, = 0.034, respectively). rs17561 was associated with single IA susceptibility (dominant model: OR = 0.52, 95% CI = 0.31-0.85, = 0.040). The rs3181216 polymorphism was associated with single IA susceptibility in the recessive model (OR = 0.41, 95% CI = 0.18-0.93, = 0.033). The rs2195940 polymorphism was associated with multiple IAs susceptibility (dominant model: OR = 0.28, 95% CI = 0.09-0.89, = 0.031; additive model: OR = 0.28, 95% CI = 0.09-0.90, = 0.032). rs1799964 was associated with multiple IAs susceptibility in the dominant model (OR = 0.54, 95% CI = 0.30-0.97, = 0.040). No associations were found between other polymorphisms and IA susceptibility. Therefore, , , and gene polymorphisms are associated with IA susceptibility in a Chinese population.
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http://dx.doi.org/10.1155/2021/8865601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826207PMC
January 2021