Publications by authors named "Meng Xia"

478 Publications

Regulatory T Cell-Related Gene Biomarkers in the Deterioration of Atherosclerosis.

Front Cardiovasc Med 2021 20;8:661709. Epub 2021 May 20.

Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Regulatory T cells (Tregs) have shown to be protective against the development of atherosclerosis, a major pathological cause for cardiovascular events. Here, we aim to explore the roles of Tregs-related genes in atherosclerosis deterioration. We downloaded the gene expression profile of 29 atherosclerotic samples from the Gene Expression Omnibus database with an accession number of GSE28829. The abundance of Tregs estimated by the CIBERSORT algorithm was negatively correlated with the atherosclerotic stage. Using the limma test and correlation analysis, a total of 159 differentially expressed Tregs-related genes (DETregRGs) between early and advanced atherosclerotic plaques were documented. Functional annotation analysis using the DAVID tool indicated that the DETregRGs were mainly enriched in inflammatory responses, immune-related mechanisms, and pathways such as complement and coagulation cascades, platelet activation, leukocyte trans-endothelial migration, vascular smooth muscle contraction, and so on. A protein-protein interaction network of the DETregRGs was then constructed, and five hub genes (, and ) were derived from the network with node degrees ≥20. The expression patterns of these hub DETregRGs were further validated in several independent datasets. Finally, a single sample scoring method was used to build a gene signature for the five DETregRGs, which could distinguish patients with myocardial infarction from those with stable coronary disease. The results of this study will improve our understanding about the Tregs-associated molecular mechanisms in the progression of atherosclerosis and facilitate the discovery of novel biomarkers for acute cardiovascular events.
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http://dx.doi.org/10.3389/fcvm.2021.661709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172618PMC
May 2021

Change in triglyceride-glucose index predicts the risk of cardiovascular disease in the general population: a prospective cohort study.

Cardiovasc Diabetol 2021 05 26;20(1):113. Epub 2021 May 26.

China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, No.119 South 4th Ring West Road, Fengtai District, Beijing, 100070, China.

Background: Previous studies has shown a significant relationship between baseline triglyceride-glucose (TyG) index and subsequent cardiovascular disease (CVD). However, the effect of longitudinal changes in TyG index on the risk of CVD remains uncertain. This study aimed to investigate the association between change in TyG index and the risk of CVD in the general population.

Methods: The current study included 62,443 Chinese population who were free of CVD. The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2], and change in TyG index was defined as the difference between the TyG index in 2010 and that in 2006. Multivariable-adjusted Cox proportional hazard models and restricted cubic spline analysis were used to examine the association between change in TyG index and the risk of CVD.

Results: During a median follow-up of 7.01 years, 2530 (4.05%) incident CVD occurred, including 2018 (3.23%) incident stroke and 545 (0.87%) incident myocardial infarction (MI). The risk of developing CVD increased with the quartile of change in TyG index, after adjustment for multiple potential confounders, the hazard ratios for the Q4 group versus the Q1 group were 1.37 (95% confidence interval [CI], 1.21-1.54) for the overall CVD, 1.38 (95% CI, 1.19-1.60) for stroke, and 1.36 (95% CI, 1.05-1.76) for MI. Restricted cubic spline analysis also showed a cumulative increase in the risk of CVD with increases in the magnitude of change in TyG index. The addition of change in TyG index to a baseline risk model for CVD improved the C-statistics (P = 0.0097), integrated discrimination improvement value (P < 0.0001), and category-free net reclassification improvement value (P < 0.0001). Similar results were observed for stroke and MI.

Conclusions: Substantial changes in TyG index independently predict the risk of CVD in the general population. Monitoring long-term changes in TyG may assist with in the early identification of individuals at high risk of CVD.
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http://dx.doi.org/10.1186/s12933-021-01305-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157734PMC
May 2021

A Fifteen-Gene Classifier to Predict Neoadjuvant Chemotherapy Responses in Patients with Stage IB to IIB Squamous Cervical Cancer.

Adv Sci (Weinh) 2021 05 18;8(10):2001978. Epub 2021 Mar 18.

Department of Obstetrics and Gynecology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Jiefang Avenue 1095# Wuhan Hubei 430030 China.

Neoadjuvant chemotherapy (NACT) remains an attractive alternative for controlling locally advanced cervical cancer. However, approximately 15-34% of women do not respond to induction therapy. To develop a risk stratification tool, 56 patients with stage IB-IIB cervical cancer are included in 2 research centers from the discovery cohort. Patient-specific somatic mutations led to NACT non-responsiveness are identified by whole-exome sequencing. Next, CRISPR/Cas9-based library screenings are performed based on these genes to confirm their biological contribution to drug resistance. A 15-gene classifier is developed by generalized linear regression analysis combined with the logistic regression model. In an independent validation cohort of 102 patients, the classifier showed good predictive ability with an area under the curve of 0.80 (95% confidence interval (CI), 0.69-0.91). Furthermore, the 15-gene classifier is significantly associated with patient responsiveness to NACT in both univariate (odds ratio, 10.8; 95% CI, 3.55-32.86; = 2.8 × 10) and multivariate analysis (odds ratio, 17.34; 95% CI, 4.04-74.40; = 1.23 × 10) in the validation set. In conclusion, the 15-gene classifier can accurately predict the clinical response to NACT before treatment, representing a promising approach for guiding the selection of appropriate treatment strategies for locally advanced cervical cancer.
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http://dx.doi.org/10.1002/advs.202001978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132153PMC
May 2021

Erratum: Long non-coding RNA LINC01116 is overexpressed in lung adenocarcinoma and promotes tumor proliferation and metastasis.

Am J Transl Res 2021 15;13(4):3919-3920. Epub 2021 Apr 15.

Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an, Shaanxi, China.

[This corrects the article on p. 4302 in vol. 12, PMID: 32913506.].
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129363PMC
April 2021

Copper Preserves Vasculature Structure and Function by Protecting Endothelial Cells from Apoptosis in Ischemic Myocardium.

J Cardiovasc Transl Res 2021 May 17. Epub 2021 May 17.

Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan, 610041, People's Republic of China.

The present study was undertaken to investigate whether Cu protects vasculatures from ischemic injury in the heart. C57/B6 mice were introduced to myocardial ischemia (MI) by permanent ligation of the left anterior descending (LAD) coronary artery. Two hours post-LAD ligation, mice were intravenously injected with a Cu-albumin (Cu-alb) solution, or saline as control. At 1, 4, or 7 days post-MI, hearts were collected for further analysis. A dramatic decrease in CD31-positive endothelial cells concomitantly with abundant apoptosis, along with obstruction of blood flow, was observed in ischemic myocardium 1 day post-MI. The early Cu-alb treatment protected CD31-positive cells from apoptosis, along with a preservation of micro-vessels and a decrease in infarct size. This early vasculature preservation ensured myocardial blood perfusion and protected cardiac contractile function until 28 days post-MI. This strategy of Cu-alb treatment immediately following MI would help develop a therapeutic approach for acute heart attack patients in a clinical setting.
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http://dx.doi.org/10.1007/s12265-021-10128-6DOI Listing
May 2021

Vascular Risk Factors, Imaging, and Outcomes in Transient Ischemic Attack/Ischemic Stroke Patients with Neuroimaging Evidence of Probable/Possible Cerebral Amyloid Angiopathy.

Oxid Med Cell Longev 2021 26;2021:9958851. Epub 2021 Apr 26.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background: In TIA/ischemic stroke patients, the clinical significance of lobar microbleeds potentially indicating cerebral amyloid angiopathy (CAA) is unknown. We assessed vascular risk factors and outcomes, including cognition, in TIA/ischemic stroke patients with neuroimaging evidence of probable/possible CAA.

Methods: This prospective cohort was conducted from August 2015 and January 2018 at 40 centers. 2625 participants were collected. Eligible participants were aged at least 55 years. Montreal Cognitive Assessment (MoCA) score is less than or equal to 26. A total of 1620 patients were included. 1604 (99.0%) and 1582 (97.7%) participants are followed up at 3 and 12 months. The primary outcomes were death or disability (mRS score, 3-6) and Montreal Cognitive Assessment (MoCA) at 3 months and 12 months. Demographic and vascular risk factors were measured at baseline (smoking, alcohol, diabetes, atrial fibrillation, hypertension, hypercholesterolemia, coronary artery disease, ischemic stroke, and transient ischemic attack). Blood samples were collected within 24 hours of admission. MRI was recommended for all patients. MoCA score was evaluated at baseline and follow-up.

Results: In total, 291/1620 patients with ischemic stroke/TIA (32.7% female and mean age, 67.8 years) had neuroimaging evidence of probable/possible CAA. Higher age, history of hypertension, atrial fibrillation, ischemic stroke, alcohol, and high glucose at the admission were more common in the patients. Mean MoCA changed from 21.4 at 3 months (SD 5.2) to 22.3 at 12 months (SD 4.7), difference 0.3 (SD 3.8). At the 3-month and 12-month follow-up, there were significant differences in age, education level, and sex among different cognitive groups. Higher age, lower education (less than high school), and female sex were the predictors of changing in MoCA score from 3 months to 12 months. Moreover, age (more than 66 years) and education (less than high school) are strongly associated with MoCA at 3- and 12-month follow-up. 30 of 286 (10.5%) and 37 of 281 (13.2%) patients had poor outcome of death or disability (modified Rankin Scale score, 3-6) at follow-up 3 and 12 months. Cortical superficial siderosis (cSS) was associated with higher mRS at follow-up. cSS status, cSS count 1-2, cSS strictly lobar, and strictly deep might be the risks of outcomes in adjusted analyses.

Conclusion: This study suggested that an increasing number of vascular risk factors and imaging markers were significantly associated with outcomes of TIA/ischemic stroke patients with CAA pattern. Male, young patients with high education should get better cognitive recovery.
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http://dx.doi.org/10.1155/2021/9958851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096555PMC
April 2021

In-hospital prognosis of first-ever noncardiogenic ischemic stroke in patients with and without indication for prestroke antiplatelet therapy: Chinese Stroke Center Alliance.

Ann Transl Med 2021 Apr;9(8):626

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background: It is unknown about the influence of prestroke antiplatelet use on early outcomes in patients with and without the indication. We aimed to evaluate the in-hospital prognosis of first-ever noncardiogenic ischemic stroke patients with and without indications of antiplatelet use for primary prevention.

Methods: This was a retrospective, observational study based on a prospective hospital-based registry (Chinese Stroke Center Alliance). Using the data with 436,660 first-ever noncardiogenic acute ischemic strokes recorded from Aug 1, 2015, to July 31, 2019, from 1,453 hospitals in China, we examined the associations between the indication for prestroke antiplatelet use and in-hospital clinical outcomes.

Results: Among 436,660 first-ever noncardiogenic ischemic stroke patients, 42,409 patients (9.7%) had a documented previous vascular indication and 394,251 (90.3%) did not. Compared to those without, patients with the indication were associated with increased prevalence of in-hospital morbid conditions, including stroke severity (OR 2.71; 95% CI: 2.62-2.81; P<0.0001), length of stay >14 days (OR 1.16; 95% CI: 1.13-1.19; P<0.0001), mortality (OR 2.20; 95% CI: 1.96-2.46, P<0.0001), and recurrence of ischemic stroke and transient ischemic attack (TIA) (OR 1.5; 95% CI: 1.43-1.59, P<0.0001). Among patients without indication, prestroke antiplatelet use was associated with lower mortality (OR 0.73, 95% CI: 0.56-0.96; P=0.0221); while among patients with indication, those receiving prestroke antiplatelet had lower odds ratios in stroke severity (P<0.0001) and disability (P=0.0003) than those who not.

Conclusions: Patients with indications of prestroke antiplatelet use were more likely to have unfavorable outcomes than those without. Prestroke antiplatelet might be associated with lower mortality, less disability, and less stroke severity in certain population groups. Future studies to improve risk prediction rules are needed to guide effective primary prevention for ischemic stroke.
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http://dx.doi.org/10.21037/atm-20-7902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106102PMC
April 2021

Chromatin accessibility governs the differential response of cancer and T cells to arginine starvation.

Cell Rep 2021 May;35(6):109101

MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.

Depleting the microenvironment of important nutrients such as arginine is a key strategy for immune evasion by cancer cells. Many tumors overexpress arginase, but it is unclear how these cancers, but not T cells, tolerate arginine depletion. In this study, we show that tumor cells synthesize arginine from citrulline by upregulating argininosuccinate synthetase 1 (ASS1). Under arginine starvation, ASS1 transcription is induced by ATF4 and CEBPβ binding to an enhancer within ASS1. T cells cannot induce ASS1, despite the presence of active ATF4 and CEBPβ, as the gene is repressed. Arginine starvation drives global chromatin compaction and repressive histone methylation, which disrupts ATF4/CEBPβ binding and target gene transcription. We find that T cell activation is impaired in arginine-depleted conditions, with significant metabolic perturbation linked to incomplete chromatin remodeling and misregulation of key genes. Our results highlight a T cell behavior mediated by nutritional stress, exploited by cancer cells to enable pathological immune evasion.
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http://dx.doi.org/10.1016/j.celrep.2021.109101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131582PMC
May 2021

An Analysis of the Potential Relationship of Triglyceride Glucose and Body Mass Index With Stroke Prognosis.

Front Neurol 2021 22;12:630140. Epub 2021 Apr 22.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

The inverse association between obesity and outcome in stroke patients (known as the obesity paradox) has been widely reported, yet mechanistic details explaining the paradox are limited. The triglyceride glucose (TYG) index has been proposed as a marker of insulin resistance. We sought to explore possible associations of the TYG index, body mass index (BMI), and stroke outcome. We identified 12,964 ischemic stroke patients without a history of diabetes mellitus from the China National Stroke Registry and classified patients as either low/normal weight, defined as a BMI <25 kg/m, or overweight/obese, defined as a BMI ≥ 25 kg/m. We calculated TYG index and based on which the patients were divided into four groups. A Cox or logistic regression model was used to evaluate the association between BMI and TYG index and its influence on stroke outcomes, including stroke recurrence all-cause mortality and poor outcome (modified Rankin Scale score of 3-6) at 12 months. Among the patients, 63.3% were male, and 36.7% were female, and the mean age of the patient cohort was 64.8 years old. The median TYG index was 8.62 (interquartile range, 8.25-9.05). After adjusting for multiple potential covariates, the all-cause mortality of overweight/obese patients was significantly lower than that of the low/normal weight patients (6.17 vs. 9.32%; adjusted hazard ratio, 0.847; 95% CI 0.732-0.981). The difference in mortality in overweight/obese and low/normal weight patients with ischemic stroke was not associated with TYG index, and no association between BMI and TYG index was found. Overweight/obese patients with ischemic stroke have better survival than patients with low/normal weight. The association of BMI and stroke outcome is not changed by TYG index.
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http://dx.doi.org/10.3389/fneur.2021.630140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101495PMC
April 2021

Prenatal exposure to ambient fine particulate matter and early childhood neurodevelopment: A population-based birth cohort study.

Sci Total Environ 2021 Sep 24;785:147334. Epub 2021 Apr 24.

Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China (Fudan University), China; Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China. Electronic address:

Although previous studies have reported the adverse effect of air pollution exposure during pregnancy on neurodevelopment in children, epidemiological evidence is limited, and the results are inconsistent. This study aimed to explore the association between prenatal ambient fine particulate matter (PM) exposure and early childhood neurodevelopment in a large birth cohort study of 4009 maternal-child pairs. Prenatal daily PM exposure concentrations at 1 km spatial revolution were estimated using high-performance machine-learning models. Neurodevelopmental outcomes of children at ages 2, 6, 12, and 24 months were assessed using the Ages and Stages Questionnaire (ASQ). Distributed lag nonlinear models were used to identify critical windows of prenatal PM exposure. General linear mixed models with binomially distributed errors were used to estimate the effect of prenatal PM exposure on suspected developmental delay (SDD) in five developmental domains based on the longitudinal design. Prenatal PM exposure was significantly associated with decreased scores for all neurodevelopmental domains of children at ages 2, 6, and 24 months. Each 10-μg/m increase in PM exposure was significantly associated with increased risk of SDD for all subjects (RR: 1.52 95% CI: 1.19, 2.03), specifically, in problem-solving domain for girls (RR: 2.23, 95% CI: 1.22, 4.35). Prenatal PM exposure in weeks 18 to 34 was significantly associated with both ASQ scores and SDDs. Our study proposed that prenatal PM exposure affected early childhood neurodevelopment evaluated with the ASQ scale. PM exposure might increase the risk of SDD for boys and girls, specifically in the problem-solving domain for girls.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147334DOI Listing
September 2021

Clopidogrel with aspirin in High-risk patients with Acute Non-disabling Cerebrovascular Events II (CHANCE-2): rationale and design of a multicentre randomised trial.

Stroke Vasc Neurol 2021 May 5. Epub 2021 May 5.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background: In patients with a minor ischaemic stroke or transient ischaemic attack (TIA), separate trials have shown that dual antiplatelet therapy with clopidogrel plus aspirin (clopidogrel-aspirin) or ticagrelor plus aspirin (ticagrelor-aspirin) are more effective than aspirin alone in stroke secondary prevention. However, these two sets of combination have not been directly compared. Since clopidogrel was less effective in stroke patients who were loss-of-function (LOF) allele carriers, whether ticagrelor-aspirin is clinically superior to clopidogrel-aspirin in this subgroup of patients with stroke is unclear.

Aim: To describe the rationale and design considerations of the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE-2) trial.

Design: CHANCE-2 is a randomised, double-blind, double-dummy, placebo-controlled, multicentre trial that compares two dual antiplatelet strategies for minor stroke or TIA patients who are allele carriers: ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily on days 2-90) or clopidogrel (300 mg loading dose on day 1 followed by 75 mg daily on days 2-90), plus open-label aspirin with a dose of 75-300 mg on day 1 followed by 75 mg daily on day 2-21. All will be followed for 1 year.

Study Outcomes: The primary efficacy outcome is any stroke (ischaemic or haemorrhagic) within 3 months and the primary safety outcome is any severe or moderate bleeding event within 3 months.

Discussion: The CHANCE-2 trial will evaluate whether ticagrelor-aspirin is superior to clopidogrel-aspirin for minor stroke or TIA patients who are LOF allele carriers.

Trial Registration Number: NCT04078737.
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http://dx.doi.org/10.1136/svn-2020-000791DOI Listing
May 2021

Analytical validation of GMEX rapid point-of-care genotyping system for the CHANCE-2 trial.

Stroke Vasc Neurol 2021 May 5. Epub 2021 May 5.

China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

Background And Purpose: Rapid genotyping is useful for guiding early antiplatelet therapy in patients with high-risk nondisabling ischaemic cerebrovascular events (HR-NICE). Conventional genetic testing methods used in genotype-guided antiplatelet therapy for patients with HR-NICE did not satisfy the needs of the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE)-2 trial. Therefore, we developed the rapid-genotyping GMEX (point-of-care) system to meet the needs of the CHANCE-2 trial.

Methods: Healthy individuals and patients with history of cardiovascular diseases (n=408) were enrolled from six centres of the CHANCE-2 trial. We compared the laboratory-based genomic test results with Sanger sequencing test results for accuracy verification. Next, we demonstrated the accuracy, timeliness and clinical operability of the GMEX system compared with laboratory-based technology (YZY Kit) to verify whether the GMEX system satisfies the needs of the CHANCE-2 trial.

Results: Genotypes reported by the GMEX system showed 100% agreement with those determined by using the YZY Kit and Sanger sequencing for all three alleles (*2, *3 and *17) tested. The average result's turnaround times for the GMEX and YZY Kit methods were 85.0 (IQR: 85.0-86.0) and 1630.0 (IQR: 354.0-7594.0) min (p<0.001), respectively.

Conclusions: Our data suggest that the GMEX system is a reliable and feasible point-of-care system for rapid genotyping for the CHANCE-2 trial or related clinical and research applications.
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http://dx.doi.org/10.1136/svn-2021-000874DOI Listing
May 2021

Imaging Parameters Predict Recurrence After Transient Ischemic Attack or Minor Stroke Stratified by ABCD Score.

Stroke 2021 Jun 5;52(6):2007-2015. Epub 2021 May 5.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (J.J., Y.S., A.W., Y.Z., Y.J., L.L., X.Z., Yilong Wang, Z.L., H.L., X.M., Yongjun Wang).

Background And Purpose: Whether imaging parameters would independently predict stroke recurrence in low-risk minor ischemic stroke (MIS) or transient ischemic attack (TIA) according to traditional score system (such as ABCD score, which was termed on the basis of the initials of the five factors: age, blood pressure, clinical features, duration, diabetes) remains unclear. We sought to evaluate the association between imaging parameters and 1-year stroke recurrence in patients with TIA or MIS in different risk stratum stratified by ABCD score.

Methods: We included patients with TIA and MIS (National Institutes of Health Stroke Scale score ≤3) with complete baseline vessel and brain imaging data from the Third China National Stroke Registry III. Patients were categorized into different risk groups based on ABCD score (low risk, 0-3; moderate risk, 4-5; and high risk, 6-7). The primary outcome was stroke recurrence within 1 year. Multivariable Cox proportional-hazards regression models were used to assess whether imaging parameters (large artery stenosis, infarction number) were independently associated with stroke recurrence.

Results: Of the 7140 patients included, 584 patients experienced stroke recurrence within 1 year. According to the ABCD score, large artery stenosis was associated with higher stroke recurrence in both low-risk (adjusted hazard ratio, 1.746 [95% CI, 1.200-2.540]) and moderate-risk group (adjusted hazard ratio, 1.326 [95% CI, 1.042-1.687]) but not in the high-risk group (>0.05). Patients with multiple acute infarctions or single acute infarction had a higher risk of recurrent stroke than those with no infarction in both low- and moderate-risk groups, but not in the high-risk group.

Conclusions: Large artery stenosis and infarction number were independent predictors of 1-year stroke recurrence in low-moderate risk but not in high-risk patients with TIA or MIS stratified by ABCD score. This finding emphasizes the importance of early brain and vascular imaging evaluation for risk stratification in patients with TIA or MIS.
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http://dx.doi.org/10.1161/STROKEAHA.120.032424DOI Listing
June 2021

Investigating function of long noncoding RNA of HOTAIRM1 in progression of SKOV3 ovarian cancer cells.

Drug Dev Res 2021 May 3. Epub 2021 May 3.

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, Sichuan, China.

Ovarian cancer is one of the most heterogeneous malignancies in the field of gynecologic oncology. Deregulation of long noncoding RNAs (lncRNAs) is implicated in carcinogenesis. Therefore, the present study was conducted to investigate the possible role of lncRNA of HOXA transcript antisense intergenic RNA myeloid-specific 1(HOTAIRM1) in progression of SKOV3 cells in ovarian cancer and also its underlying molecular mechanisms. HOTAIRM1 expression level will be measured by real-time polymerase chain reaction (PCR) in SKOV3 cells. For determining the effect of HOTAIRM1 silencing on progression of SKOV3 cells, siHOTAIRM1 will be designed and transfected into cells using a liposomal approach. MTT and trypan blue assays will be used to determine the effect of HOTAIRM1 silencing on cell proliferation. Apoptosis of the cells will be detected by flow cytometry. Furthermore, expressions of apoptosis-related genes and Wnt pathway-related proteins and genes will be analyzed by Western blot and real-time PCR. HOTAIRM1 was overexpressed in SKOV3 cells. Silencing of HOTAIRM1 alleviated cell proliferation, and increased cell apoptosis of SKOV3 cells. Moreover, siHOTAIRM1 significantly increased expression of pro-apoptotic agents, such as Bad and Bax, while it decreased expressions of Bid and Bcl-2 (anti-apoptotic agents). Also, silencing of HOTAIRM1 resulted in a suppressed expression of Wnt pathway-related proteins and also expression of its downstream target gene, matrix metalloproteinase 9(MMP9). Our findings provided new insights into function of lncRNA of HOTAIRM1 in progression of ovarian cancer by modulating Wnt pathway and its downstream target gene, MMP9.
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http://dx.doi.org/10.1002/ddr.21821DOI Listing
May 2021

LCT-3d Induces Oxidative Stress-Mediated Apoptosis by Upregulating Death Receptor 5 in Gastric Cancer Cells.

Front Oncol 2021 16;11:658608. Epub 2021 Apr 16.

Key Laboratory of Advanced Technology for Drug Preparation, Ministry of Education, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.

Gastric cancer is a global health problem. In this study, we investigate the role of a novel Indole derivative, named LCT-3d, in inhibiting the growth of gastric cancer cells by MTT assay. The Western blotting results showed that LCT-3d modulated the mitochondrial-related proteins and Cleaved-Caspases 3/9, to induce cell apoptosis. The up-regulation of Death receptor 5 (DR5) in MGC803 cells was observed with LCT-3d treatment. Knockdown of DR5 on MGC803 cells partially reversed the LCT-3d-induced mitochondrial apoptosis. The level of Reactive Oxygen Species (ROS) in MGC803 cells was increased with LCT-3d treatment and could be blocked with the pretreatment of the ROS inhibitor N-Acetylcysteine (NAC). The results demonstrate that the elevating ROS can up-regulate the expression of DR5, resulting in apoptosis mitochondrial pathway. Although the nuclear factor erythroid-2 related factor 2 (Nrf2) pathway served an important role in protecting gastric cancer cells against the injury of ROS, it can't reverse LCT-3d-induced cell apoptosis. Taken together, our study showed that LCT-3d induced apoptosis DR5-mediated mitochondrial apoptotic pathway in gastric cancer cells. LCT-3d could be a novel lead compound for development of anti-cancer activity in gastric cancer.
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http://dx.doi.org/10.3389/fonc.2021.658608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085419PMC
April 2021

Serum Phosphate and 1-Year Outcome in Patients With Acute Ischemic Stroke and Transient Ischemic Attack.

Front Neurol 2021 14;12:652941. Epub 2021 Apr 14.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

To determine the association between serum phosphate level and 1-year clinical outcomes in patients with acute ischemic stroke and transient ischemic attack. We included 7,353 patients with acute ischemic stroke and transient ischemic attack from the China National Stroke Registry III for analysis. Participants were divided into 4 groups according to serum phosphate quartiles. Composite end point included recurrent stroke, myocardial infarction, other ischemic vascular events, and all-cause mortality. Poor functional outcome is defined as modified Rankin Scale score of 3 to 6. Multivariable Cox regression or logistic regression was used to evaluate the independent association of serum phosphate with 1-year all-cause mortality, recurrent stroke, composite end point and poor functional outcome. The mean age of the included 7,353 patients was 62.5 years, and 68.6% of them were men. Plotting hazard ratios over phosphate levels suggested a U-shaped association especially for recurrent stroke and composite end point, and therefore the third quartile group was set as reference group. Compared with the third quartile of phosphate (1.06-1.20 mmol/L), the adjusted hazard ratios/odds ratios (95% CI) of the lowest quartile (<0.94 mmol/L) were 0.98 (0.67-1.42) for all-cause mortality, 1.31 (1.05-1.64) for stroke recurrence, 1.26 (1.02-1.57) for composite end point, and 1.27 (1.01-1.61) for poor functional outcome, and the adjusted odds ratio of the highest quartile (≥1.2 mmol/L) was 1.40 (1.11-1.77) for poor functional outcome. Serum phosphate may be an independent predictor of stroke recurrence, composite end point and poor functional outcome after ischemic stroke.
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http://dx.doi.org/10.3389/fneur.2021.652941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079723PMC
April 2021

A Phase I Study of an IDO-1 Inhibitor (LY3381916) as Monotherapy and in Combination With an Anti-PD-L1 Antibody (LY3300054) in Patients With Advanced Cancer.

J Immunother 2021 Apr 28. Epub 2021 Apr 28.

Jules Bordet Institute, Brussels University Hospital Antwerp, Edegem, Belgium Drug Development Department (DITEP), Gustave Roussy Institute, Villejuif, France Department of Hematology-Oncology, Indiana University Simon Comprehensive Cancer Center Eli Lilly and Company Indiana University School of Medicine, Indianapolis, IN Ghent University Hospital, Ghent, Belgium Eli Lilly and Company, New York, NY Eli Lilly and Company, Stockholm, Sweden Eli Lilly and Company, Surrey, UK Sarah Cannon Research Institute Tennessee Oncology, Nashville, TN.

LY3381916 is an orally available, highly selective, potent inhibitor of indoleamine 2,3-dioxygenase 1. This study explored the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of LY3381916 monotherapy and in combination with a programmed death-ligand 1 (PD-L1) inhibitor (LY3300054) in patients with advanced solid tumors. During dose escalation, patients received escalating doses of LY3381916 at 60-600 mg once daily (qd) and 240 mg twice daily in monotherapy (n=21) and in combination with PD-L1 inhibitor at 700 mg every 2 weeks (n=21). A modified toxicity probability interval method was used to guide dose escalation. Dose-limiting toxicities occurred in 3 patients; 1 at LY3381916 240 mg twice daily (alanine aminotransferase/aspartate aminotransferase increase and systemic inflammatory response syndrome) and 2 at LY3381916 240 mg qd in combination with PD-L1 inhibitor (fatigue and immune-related hepatitis). LY3381916, at the recommended phase II dose, 240 mg qd, in combination with PD-L1 inhibitor, produced maximal inhibition of indoleamine 2,3-dioxygenase 1 activity in plasma and tumor tissue, and led to an increase of CD8 T cells in tumor tissue. In the combination dose expansion cohorts, 14 triple-negative breast cancer and 4 non-small cell lung cancer patients were enrolled. Treatment-related liver toxicity (grade ≥2 alanine aminotransferase/aspartate aminotransferase increase or immune-related hepatitis) was the most prominent adverse event in triple-negative breast cancer patients (n=5, 35.7%). Best response was stable disease. These preliminary data suggest an alternative dose level of LY3381916 is needed for the combination with PD-L1 inhibitor. The combination clinical activity was limited in this study.
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http://dx.doi.org/10.1097/CJI.0000000000000368DOI Listing
April 2021

Association of Polyvascular Disease and Elevated Interleukin-6 With Outcomes in Acute Ischemic Stroke or Transient Ischemic Attack.

Front Neurol 2021 13;12:661779. Epub 2021 Apr 13.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Polyvascular disease (PolyVD) and interleukin (IL)-6 are associated with poor outcomes in patients with stroke respectively. However, whether combined PolyVD and elevated IL-6 levels would increase the risk of poor outcomes of stroke patients is yet unclear. Data were obtained from the Third China National Stroke Registry (CNSR-III). PolyVD was defined as acute ischemic stroke (AIS) or transient ischemic attack (TIA) with coronary artery disease (CAD) and/or peripheral artery disease (PAD). Patients were divided into four groups according to the combination of vascular beds number (non-PolyVD or PolyVD) and IL-6 levels (IL-6 < 2.64 pg/mL or IL-6 ≥ 2.64 pg/mL). The primary outcome was a recurrent stroke at 1-year follow-up. Cox proportional hazard models were employed to identify the association of the combined effect of PolyVD and IL-6 with the prognosis of patients. A total of 10,773 patients with IL-6 levels and 1-year follow-up were included. The cumulative incidence of recurrent stroke was 9.87% during the 1-year follow-up. Compared to non-PolyVD and IL-6<2.64 pg/mL patients, patients had non-PolyVD with IL-6 ≥ 2.64 pg/mL (HR 1.245 95%CI 1.072-1.446; < 0.001) and PolyVD with IL-6 <2.64 pg/mL (HR 1.251 95%CI 1.002-1.563; = 0.04) were associated with an increased risk of recurrent stroke during 1-year follow-up. Likewise, patients with PolyVD and IL-6 ≥ 2.64 pg/mL (HR 1.290; 95% CI 1.058-1.572; = 0.01) had the highest risk of recurrent stroke at 1-year follow-up among groups. PolyVD and elevated IL-6 levels are both associated with poor outcomes in patients with AIS or TIA. Moreover, the combination of them increases the efficiency of stroke risk stratification compared with when used alone. More attention and intensive treatment should be given to those patients with both PolyVD and elevated IL-6 levels.
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http://dx.doi.org/10.3389/fneur.2021.661779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076541PMC
April 2021

Hybrid double-network hydrogel for highly stretchable, excellent sensitive, stabilized, and transparent strain sensors.

J Biomater Sci Polym Ed 2021 Apr 26:1-14. Epub 2021 Apr 26.

Collaborative Innovation Center for Advanced Organic Chemical Materials Co-constructed by the Province and Ministry, Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei Key Laboratory of Polymer Materials (Hubei University), College of Chemistry and Chemical Engineering, Hubei University, Wuhan, China.

Nowadays, great effort has been devoted to fabricate flexible wearable sensor with high stretchability, moderate modulus, favorable durability, excellent transparency, and satisfactory sensitivity. In this work, we report the preparation of a hybrid double-network (DN) hydrogel by a simple one-pot method. First, chitosan was added into an AlCl solution to form Al-chitosan complex (CS-Al). Second, the hybrid CS/Al-poly(acrylamide) (PAM) double-network (DN) hydrogels were constructed in-situ polymerization of acrylamide (AM) in present of Al-chitosan complex. Thanks to the existence of electrically conductive CS-Al networks, the resulting hybrid DN hydrogel exhibits excellent stretchability, fatigue resistance, transparency, and conductivity. Furthermore, the CS/Al-PAM DN hydrogel could be used as strain sensor, and demonstrates many desired virtues, including satisfactory sensitivity (gauge factors of 1.7 to 12.1), wide detection range (up to 1500%), low limit of discernment (1% strain), high reliability, and excellent durability (1000 cycles). More significantly, the manufactured hydrogel-based strain sensor can be employed as wearable devices to precisely detect various human movements.
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http://dx.doi.org/10.1080/09205063.2021.1922170DOI Listing
April 2021

Developing indices to identify hotspots of skin cancer vulnerability among the Non-Hispanic White population in the United States.

Ann Epidemiol 2021 Apr 22;59:64-71. Epub 2021 Apr 22.

Environmental Health Tracking Section, Division of Environmental Health Practice and Science, National Center for Environmental Health (NCEH), Centers for Disease Control and Prevention (CDC), Atlanta, GA. Electronic address:

Purpose: Skin cancer is the most common, yet oftentimes preventable, cancer type in the United States. Exposure to ultraviolet radiation from sunlight is the most prominent environmental risk factor for skin cancer. Besides environmental exposure, demographic characteristics such as race, age, and socioeconomic status may make some groups more vulnerable. An exploratory spatial clustering method is described for identifying clusters of vulnerability to skin cancer incidence and mortality based on composite indices, which combine data from environmental and demographic risk factors.

Methods: Based on county-level ultraviolet data and demographic risk factors, two vulnerability indices for skin cancer were generated using an additive percentile rank approach. With these indices, univariate local Moran's I spatial autocorrelation identified significant clusters, or hotspots, of neighboring counties with high overall vulnerability indices. Clusters were identified separately for skin cancer incidence and mortality.

Results: Counties with high vulnerabilities were spatially distributed across the United States in a pattern that generally increased to the South and West. Clusters of counties with high skin cancer incidence vulnerability were mostly observed in Utah and Colorado, even with highly conservative levels of significance. Meanwhile, clusters for skin cancer mortality vulnerability were observed in southern Alabama and west Florida as well as across north Alabama, north Georgia and up through the Tennessee-North Carolina area.

Conclusions: Future skin cancer research and screening initiatives may use these innovative composite vulnerability indices and identified clusters to better target resources based on anticipated risk from underlying demographic and environmental factors.
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http://dx.doi.org/10.1016/j.annepidem.2021.04.004DOI Listing
April 2021

Serum calcium and long-term outcome after ischemic stroke: Results from the China National stroke registry III.

Atherosclerosis 2021 05 29;325:24-29. Epub 2021 Mar 29.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China. Electronic address:

Background And Aims: Serum calcium abnormality is associated with adverse cardiovascular outcomes, but the effects of serum calcium level on stroke outcomes remain unknown. We aimed to assess the relationship between serum calcium level and 1-year outcomes in patients with acute ischemic stroke and transient ischemic attack.

Methods: We included 9375 stroke patients from the China National Stroke Registry III for analysis. Participants were divided into 4 groups according to albumin corrected-calcium quartiles. Composite end point comprised recurrent stroke, myocardial infarction, other ischemic vascular events, and all-cause mortality. Multivariable Cox or logistic regression was used to evaluate the independent association of albumin corrected-calcium with all-cause mortality, recurrent stroke, composite end point, and poor functional outcome (modified Rankin Scale score ≥3).

Results: Compared with the lowest calcium quartile (<2.16 mmol/L), the adjusted hazard ratio (95% CI) of the top quartile (≥2.31 mmol/L) was 1.56 (1.11-2.18) for all-cause mortality, 1.06 (0.87-1.28) for recurrent stroke and 1.08 (0.90-1.01) for composite end point, and the adjusted odds ratio for poor functional outcome was 1.18 (0.96-1.44). The addition of serum calcium to conventional risk factors improved risk prediction of all-cause mortality, leading to a small but significant increase in C-statistics and reclassification with non-significant integrated discrimination improvement (C-statistics, p = 0.02; net reclassification index 11.8%, p = 0.038; integrated discrimination improvement 0.08%, p = 0.42).

Conclusions: High serum calcium levels at baseline were associated with all-cause mortality at 1-year after ischemic stroke, suggesting that serum calcium may be a potential prognostic biomarker and therapeutic target for ischemic stroke.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.03.030DOI Listing
May 2021

[Corrigendum] GINS2 is a novel prognostic biomarker and promotes tumor progression in early‑stage cervical cancer.

Oncol Rep 2021 May 22;45(5). Epub 2021 Apr 22.

Department of Gynecology and Obstetrics, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, P.R. China.

Subsequently to the publication of the above article, the authors have realized that Figs. 2 and 6 each contained an incorrectly assembled data panel: Essentially, a couple of the data panels had been inadvertently selected twice for these figures. The corrected versions of Figs 2 and 6, including the correct data for the H&E staining of the tissue of patient 4 in Fig. 2C and the invaded cells of RNAi#2 of the Siha cell line in Fig. 6C, are shown below and on the next page. All the authors agree to the publication of this Corrigendum, and they thank the Editor of for allowing them the opportunity to publish it. Furthermore, they apologize to the readership for any inconvenience caused. [The original article was published in  37: 2652‑2662, 2017; DOI: 10.3892/or.2017.5573].
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http://dx.doi.org/10.3892/or.2021.8016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020209PMC
May 2021

Association of Trimethylamine N-Oxide and Its Precursor With Cerebral Small Vessel Imaging Markers.

Front Neurol 2021 1;12:648702. Epub 2021 Apr 1.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

High plasma levels of trimethylamine N-oxide (TMAO) and its precursor choline have been linked to stroke; however, their association with cerebral small vessel disease remains unclear. Here we evaluated the association of plasma levels of TMAO and choline with imaging markers of cerebral small vessel disease, including white matter hyperintensities, lacunes, and cerebral microbleeds. We performed a baseline cross-sectional analysis of a multicenter hospital-based cohort study from 2015 to 2018. The data were collected from 30 hospitals in China and included 1,098 patients with ischemic stroke/transient ischemic attack aged ≥18 years. White matter hyperintensities, lacunes, and cerebral microbleeds were evaluated with the patients' demographic, clinical, and laboratory information removed. White matter hyperintensities were rated using the Fazekas visual grading scale, while the degree of severity of the lacunes and cerebral microbleeds was defined by the number of lesions. Increased TMAO levels were associated with severe white matter hyperintensities [adjusted odds ratio (aOR) for the highest vs. lowest quartile, 1.5; 95% confidence interval (CI), 1.0-2.1, = 0.04]. High TMAO levels were more strongly associated with severe periventricular white matter hyperintensities (aOR for the highest vs. lowest quartile, 1.6; 95% CI, 1.1-2.3, = 0.009) than deep white matter hyperintensities (aOR for the highest vs. lowest quartile, 1.3; 95% CI, 0.9-1.9, = 0.16). No significant association was observed between TMAO and lacunes or cerebral microbleeds. Choline showed trends similar to that of TMAO in the association with cerebral small vessel disease. In patients with ischemic stroke or transient ischemic attack, TMAO and choline appear to be associated with white matter hyperintensities, but not with lacunes or cerebral microbleeds; TMAO and choline were associated with increased risk of a greater periventricular, rather than deep, white matter hyperintensities burden.
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http://dx.doi.org/10.3389/fneur.2021.648702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047127PMC
April 2021

Gut Microbiota in Lupus: a Butterfly Effect?

Curr Rheumatol Rep 2021 Apr 16;23(4):27. Epub 2021 Apr 16.

Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, The Ministry of Education Key Laboratory, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuai-Fu-Yuan, Dong-Cheng District, Beijing, 100730, China.

Purpose Of Review: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that typically displays chronic inflammatory tissue damage and miscellaneous circulatory autoantibodies, as well as distinctive type 1 interferon signatures. The etiology of SLE is unclear and currently is attributed to genetic predisposition and environmental triggers. Gut microbiota has recently been considered a critical environmental pathogenic factor in immune-related disorders, and studies are ongoing to uncover the key pathogens and the imputative mechanisms. Fundamental advancements on the role of the microbiota in SLE pathology have been achieved in recent years and are summarized in this review.

Recent Findings: Recent findings suggested that gut commensals could propagate autoimmunity via molecular mimicry in which ortholog-carrying microbes cross-activate autoreactive T/B cells and trigger the response against host autoantigens, or via bystander activation by stimulating antigen-presenting cells that present autoantigens and enhancing the expression of co-stimulatory molecules and cytokines, thus leading to the loss of self-tolerance and the production of autoantibodies. Additionally, the break of gut barrier and the translocation of gut commensals to inner organs can trigger immune dysregulation and inappropriate systemic inflammation. All these microbiota-mediated mechanisms could contribute to lupus immunopathogenesis and promote disease development in susceptible individuals. Evidence of the causative role of disturbed gut microbiome in SLE is still limited, and the related molecular mechanisms and pathways are largely elusive. However, the modification of gut microbiota, such as pathobiont vaccine, special diet, restricted consortium transplantation, as well as regulatory metabolites supplementation, might be promising strategies for lupus prophylaxis and treatment.
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http://dx.doi.org/10.1007/s11926-021-00986-zDOI Listing
April 2021

Clopidogrel Plus Aspirin in Patients With Different Types of Single Small Subcortical Infarction.

Front Neurol 2021 29;12:631220. Epub 2021 Mar 29.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

We aim to investigate the effects and safety of clopidogrel plus aspirin in patients with different types of single small subcortical infarction (SSSI) in the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. SSSI was defined as single DWI lesion of ≤2.0 cm. Patients with SSSI were divided into SSSI + PAD (parent artery disease) and SSSI - PAD, according to the stenosis of the parent artery. The efficacy outcome was stroke recurrence during 90-day follow-up. Cox proportional hazards models or logistic regression models were used to assess the interaction of the treatment effects of clopidogrel plus aspirin vs. aspirin alone among patients with and without PAD. Among 338 patients with SSSI included in the subanalysis, 105 were with PAD and 233 without. The efficacy of clopidogrel plus aspirin compared with aspirin alone on any stroke was consistent between patients with [adjusted hazard ratio (HR) 0.84; 95% confidence interval (CI), 0.25-2.75] and without PAD (adjusted HR 1.03; 95% CI, 0.40-2.68, interaction = 0.83). In patients with SSSI + PAD, the rate of stroke recurrence in those treated with dual antiplatelet therapy and mono antiplatelet therapy was not significantly different (10.9 vs. 13.6%, = 0.77). The number of bleeding events was similar between the clopidogrel-aspirin group and aspirin group regardless of SSSI + PAD or SSSI - PAD. There was no significant difference in the efficacy of clopidogrel plus aspirin compared with aspirin alone between patients with SSSI + PAD and SSSI - PAD in the CHANCE trial. Studies in other populations and with adequate power are needed to further verify such findings.
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http://dx.doi.org/10.3389/fneur.2021.631220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039512PMC
March 2021

Association Analysis of Hyperlipidemia with the 28-Day All-Cause Mortality of COVID-19 in Hospitalized Patients.

Chin Med Sci J 2021 Mar;36(1):17-26

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430071, China.

Objective This study aimed to determine the association of hyperlipidemia with clinical endpoints among hospitalized patients with COVID-19, especially those with pre-existing cardiovascular diseases (CVDs) and diabetes. Methods This multicenter retrospective cohort study included all patients who were hospitalized due to COVID-19 from 21 hospitals in Hubei province, China between December 31, 2019 and April 21, 2020. Patients who were aged < 18 or ≥ 85 years old, in pregnancy, with acute lethal organ injury (e.g., acute myocardial infarction, severe acute pancreatitis, acute stroke), hypothyroidism, malignant diseases, severe malnutrition, and those with normal lipid profile under lipid-lowering medicines (e.g., statin, niacin, fenofibrate, gemfibrozil, and ezetimibe) were excluded. Propensity score matching (PSM) analysis at 1:1 ratio was performed to minimize baseline differences between patient groups of hyperlipidemia and non-hyperlipidemia. PSM analyses with the same strategies were further conducted for the parameters of hyperlipidemia in patients with increased triglyceride (TG), increased low-density lipoprotein cholesterol (LDL-C), and decreased high-density lipoprotein cholesterol (HDL-C). Mixed-effect Cox model analysis was performed to investigate the associations of the 28-days all-cause deaths of COVID-19 patients with hyperlipidemia and the abnormalities of lipid parameters. The results were verified in male, female patients, and in patients with pre-existing CVDs and type 2 diabetes. Results Of 10 945 inpatients confirmed as COVID-19, there were 9822 inpatients included in the study, comprising 3513 (35.8%) cases without hyperlipidemia and 6309 (64.2%) cases with hyperlipidemia. Based on a mixed-effect Cox model after PSM at 1:1 ratio, hyperlipidemia was not associated with increased or decreased 28-day all-cause death [adjusted hazard ratio (), 1.17 (95% , 0.95-1.44), =0.151]. We found that the parameters of hyperlipidemia were not associated with the risk of 28-day all-cause mortality [adjusted , 1.23 (95% , 0.98-1.55), = 0.075 in TG increase group; 0.78 (95% , 0.57-1.07), = 0.123 in LDL-C increase group; and 1.12 (95% , 0.9-1.39), = 0.299 in HDL-C decrease group, respectively]. Hyperlipidemia was also not significantly associated with the increased mortality of COVID-19 in patients accompanied with CVDs or type 2 diabetes, and in both male and female cohorts. Conclusion Our study support that the imbalanced lipid profile is not significantly associated with the 28-day all-cause mortality of COVID-19 patients, even in those accompanied with CVDs or diabetes. Similar results were also obtained in subgroup analyses of abnormal lipid parameters. Therefore, hyperlipidemia might be not a major causative factor for poor outcome of COVID-19, which provides guidance for the intervention of inpatients during the epidemic of COVID-19.
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http://dx.doi.org/10.24920/003866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041136PMC
March 2021

Complete mitochondrial genome of from wuhu, China (Rotifera, Brachionidae).

Mitochondrial DNA B Resour 2021 Mar 26;6(3):1194-1196. Epub 2021 Mar 26.

Public Research Lab of Hainan Medical University, Haikou, China.

The complete mitochondrial genome of was sequenced using primers design, clone culture, DNA extraction, LONG-PCR amplification, purification and clone sequencing. We found that it is composed of two circular chromosomes, designated mtDNA I (11,398 bp) and mtDNA II (12,820 bp). The gene content of the mitochondrial genome was similar to that of the previously reported mitochondrial genome of . It contained 22 tRNA genes, 2 rRNA genes and 12 protein-coding genes (PCGs). Four of the 12 PCGs had an incomplete stop codons, TA(cob, atp6, nd3)or T(cox3). The A + T content of mitochondrial genome was apparently higher (mtDNA-I 70.2% and mtDNA II 70.4%) than that of the mitochondrial genome of (mtDNA-I 63.9% and mtDNA-II 62.9%).
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http://dx.doi.org/10.1080/23802359.2021.1903351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008871PMC
March 2021

Cumulative burden of lipid profiles predict future incidence of ischaemic stroke and residual risk.

Stroke Vasc Neurol 2021 Apr 7. Epub 2021 Apr 7.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

Objectives: Incident ischaemic stroke (IS) risk may increase not only with lipids concentration but also with longer duration of exposure. This study aimed to investigate the impact of cumulative burden of lipid profiles on risk of incident IS.

Methods: A total of 43 836 participants were enrolled who participated in four surveys during 2006-2013. Individual cumulative lipid burden was calculated as number of years (2006-2013) multiplied by the levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C and triglyceride (TG), respectively. The primary outcome was defined as the incident IS during 2012-2017.

Results: During 4.67 years (±0.70 years) follow-up on average, we identified 1023 (2.33%) incident IS. Compared with respective reference groups, the HRs (95% CIs) of the upper tertile in cumulative TG burden, cumulative LDL-C burden, cumulative TC burden and cumulative non-HDL-C burden were 1.26 mmol/L (1.02-1.55 mmol/L), 1.47 mmol/L (1.25-1.73 mmol/L), 1.33 mmol/L (1.12-1.57 mmol/L) and 1.51 mmol/L (1.28-1.80 mmol/L) for incidence of IS, respectively. However, this association was not significant in cumulative HDL-C burden and IS (HR: 1.09; 95% CI: 0.79 to 1.52), after adjustment for confounding variables. Among 16 600 participants with low cumulative LDL-C burden, HRs (95% CI) for TC, TG, non-HDL-C and HDL-C with IS were 1.63 mmol/L (1.03-2.57 mmol/L), 1.65 mmol/L (1.19-2.31 mmol/L), 1.57 mmol/L (1.06-2.32 mmol/L) and 0.98 mmol/L (0.56-1.72 mmol/L), respectively.

Conclusions: We observed the correlation between cumulative burden of lipid profiles, except for cumulative burden of HDL-C, with the risk of incident IS. Cumulative burden of TC, TG and non-HDL-C may still predict IS in patients with low cumulative LDL-C burden.

Trial Registration Number: ChiCTR-TNRC-11001489.
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http://dx.doi.org/10.1136/svn-2020-000726DOI Listing
April 2021

Transient Receptor Potential Canonical 4 Channel in Interstitial Cells of Cajal as a Target for Control of Gastrointestinal Motility.

J Neurogastroenterol Motil 2021 Apr;27(2):302-304

The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi, China.

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http://dx.doi.org/10.5056/jnm20267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026375PMC
April 2021

GALNT2 promotes cell proliferation, migration, and invasion by activating the Notch/Hes1-PTEN-PI3K/Akt signaling pathway in lung adenocarcinoma.

Life Sci 2021 Jul 27;276:119439. Epub 2021 Mar 27.

Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China. Electronic address:

Aims: Our study aimed to investigate the function of GALNT2 in lung adenocarcinoma (LUAD).

Main Methods: We used network tools and tissue microarray immunohistochemistry to measure the expression levels of GALNT2 in LUAD. Kaplan-Meier curves and Cox regression methods were used in survival analysis. We detected the role of GALNT2 in cell lines by Cell Counting Kit-8, colony formation, transwell, and wound healing assays. We performed Western blotting to evaluate downstream protein levels.

Key Findings: GALNT2 was highly expressed in LUAD samples and indicated a poor prognosis. Knockdown of GALNT2 suppressed cell line proliferation, migration, and invasion abilities, while overexpression of GALNT2 enhanced those phenotypes. Moreover, GALNT2 activated Notch/Hes1-PTEN-PI3K/Akt signaling axis.

Significance: Our data confirmed the cancer-promoting effect of GALNT2, and might provide a new approach for LUAD therapy.
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http://dx.doi.org/10.1016/j.lfs.2021.119439DOI Listing
July 2021