Impacts of Statin Therapy Strategies on Incidence of Ischemic Cerebrovascular Events in Patients With Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Bayesian Network Meta-Analysis.

BACKGROUND: The exacerbation of neurological outcomes often occurs in aneurysmal subarachnoid hemorrhage (aSAH). Statins have been commonly used for aSAH; however, there is lack of evidence of the pharmacological efficacy of different dosages and types of statins. OBJECTIVE: To apply the Bayesian network meta-analysis to analyze the optimal dosage and type of statins for the amelioration of ischemic cerebrovascular events (ICEs) in patients with aSAH. METHODS: We developed the Bayesian network meta-analysis and systemic review to analyze the effects of statins on functional prognosis and the impacts of optimal dosage and type of statins on ICEs in patients with aSAH. The outcome variables of the analysis were the incidence of ICEs and functional prognosis. RESULTS: A total of 2569 patients with aSAH across 14 studies were included. Analysis of 6 randomized controlled trials showed that statin use significantly improved functional prognosis in patients with aSAH (risk ratio [RR], 0.73; 95% CI, 0.55-0.97). Statins significantly reduced the incidence of ICEs (RR, 0.78; 95% CI, 0.67-0.90). Pravastatin (40 mg/d) decreased the incidence ICEs compared with placebo (RR, 0.14; 95% CI, 0.03-0.65) and was ranked the most effective, presenting with a significantly lower rate of the incidence ICEs than the worst-ranked simvastatin (40 mg/d) (RR, 0.13; 95% CI, 0.02-0.79). CONCLUSION: Statins could significantly diminish the incidence of ICEs and enhance functional prognosis in patients with aSAH. Various types and dosages of statins show distinct efficacies.

Novel DNA methylation loci and genes showing pleiotropic association with Alzheimer's dementia: a network Mendelian randomization analysis.

Previous genome-wide association studies (GWAS) have identified potential genetic variants involved in the risk of Alzheimer's dementia, but their underlying biological interpretation remains largely unclear. In addition, the effects of DNA methylation and gene expression on Alzheimer's dementia are not well understood. A network summary data-based Mendelian randomization (SMR) analysis was performed integrating cis- DNA methylation quantitative trait loci (mQTL) /cis- gene expression QTL (eQTL) data in the brain and blood, as well as GWAS summarized data for Alzheimer's dementia to evaluate the pleiotropic associations of DNA methylation and gene expression with Alzheimer's dementia and to explore the complex mechanisms underpinning Alzheimer's dementia. After correction for multiple testing (false discovery rate [FDR] P < 0.05) and filtering using the heterogeneity in dependent instruments (HEIDI) test (PHEIDI>0.01), we identified dozens of DNA methylation sites and genes showing pleiotropic associations with Alzheimer's dementia. We found 22 and 16 potentially causal pathways of Alzheimer's dementia (i.e., SNP→DNA methylation→Gene expression→Alzheimer's dementia) in the brain and blood, respectively. Approximately two-thirds of the identified DNA methylation sites had an influence on gene expression and the expression of almost all the identified genes was regulated by DNA methylation. Our network SMR analysis provided evidence supporting the pleiotropic association of some novel DNA methylation sites and genes with Alzheimer's dementia and revealed possible causal pathways underlying the pathogenesis of Alzheimer's dementia. Our findings shed light on the role of DNA methylation in gene expression and in the development of Alzheimer's dementia.

Optimal Course of Statins for Patients With Aneurysmal Subarachnoid Hemorrhage: Is Longer Treatment Better? A Meta-Analysis of Randomized Controlled Trials.

Statins are used in clinical practice to prevent from complications such as cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH). However, the efficacy and safety of statins are still controversial due to insufficient evidence from randomized controlled trials and inconsistent results of the existing studies. This meta-analysis aimed to systematically review the latest evidence on the time window and complications of statins in aSAH. The randomized controlled trials in the databases of The Cochrane Library, PubMed, Web of Science, Embase, CNKI, and Wanfang from January 2005 to April 2021 were searched and analyzed systematically. Data analysis was performed using Stata version 16.0. The fixed-effects model (M-H method) with effect size risk ratio (RR) was used for subgroups with homogeneity, and the random-effects model (D-L method) with effect size odds ratio (OR) was used for subgroups with heterogeneity. The primary outcomes were poor neurological prognosis and all-cause mortality, and the secondary outcomes were cerebral vasospasm (CVS) and statin-related complications. This study was registered with PROSPERO (International Prospective Register of Systematic Reviews; CRD42021247376). Nine studies comprising 1,464 patients were included. The Jadad score of the patients was 5-7. Meta-analysis showed that poor neurological prognosis was reduced in patients who took oral statins for 14 days (RR, 0.73 [0.55-0.97]; I 2 = 0%). Surprisingly, the continuous use of statins for 21 days had no significant effect on neurological prognosis (RR, 1.04 [0.89-1.23]; I 2 = 17%). Statins reduced CVS (OR, 0.51 [0.36-0.71]; I 2 = 0%) but increased bacteremia (OR, 1.38 [1.01-1.89]; I 2 = 0%). In conclusion, a short treatment course of statins over 2 weeks may improve neurological prognosis. Statins were associated with reduced CVS. Based on the pathophysiological characteristics of CVS and the evaluation of prognosis, 2 weeks could be the optimal time window for statin treatment in aSAH, although bacteremia may increase.

Risk Factors of Psychological Responses of Chinese University Students During the COVID-19 Outbreak: Cross-sectional Web-Based Survey Study.

BACKGROUND: COVID-19 is a highly contagious and highly pathogenic disease caused by a novel coronavirus, SARS-CoV-2, and it has become a pandemic. As a vulnerable population, university students are at high risk during the epidemic, as they have high mobility and often overlook the severity of the disease because they receive incomplete information about the epidemic. In addition to the risk of death from infection, the epidemic has placed substantial psychological pressure on the public. In this respect, university students are more prone to psychological problems induced by the epidemic compared to the general population because for most students, university life is their first time outside the structure of the family, and their mental development is still immature. Internal and external expectations and academic stress lead to excessive pressure on students, and unhealthy lifestyles also deteriorate their mental health. The outbreak of COVID-19 was a significant social event, and it could potentially have a great impact on the life and the mental health of university students. Therefore, it is of importance to investigate university students' mental health status during the outbreak of COVID-19. OBJECTIVE: The principal objective of this study was to investigate the influencing factors of the psychological responses of Chinese university students during the COVID-19 outbreak. METHODS: This study used data from a survey conducted in China between February 21 and 24, 2020, and the data set contains demographic information and psychological measures including the Self-Rating Anxiety Scale, the Self-Rating Depression Scale, and the compulsive behaviors portion of the Yale-Brown Obsessive-Compulsive Scale. A total of 2284 questionnaires were returned, and 2270 of them were valid and were used for analysis. The Mann-Whitney U test for two independent samples and binary logistic regression models were used for statistical analysis. RESULTS: Our study surveyed 563 medical students and 1707 nonmedical students. Among them, 251/2270 students (11.06%) had mental health issues. The results showed that contact history of similar infectious disease (odds ratio [OR] 3.363, P=.02), past medical history (OR 3.282, P<.001), and compulsive behaviors (OR 3.525, P<.001) contributed to the risk of mental health issues. Older students (OR 0.928, P=.02), regular daily life during the epidemic outbreak (OR 0.410, P<.001), exercise during the epidemic outbreak (OR 0.456, P<.001), and concern related to COVID-19 (OR 0.638, P=.002) were protective factors for mental health issues. CONCLUSIONS: According to the study results, mental health issues have seriously affected university students, and our results are beneficial for identifying groups of university students who are at risk for possible mental health issues so that universities and families can prevent or intervene in the development of potential mental health issues at the early stage of their development.

Mendelian randomization integrating GWAS and eQTL data revealed genes pleiotropically associated with major depressive disorder.

Previous genome-wide association studies (GWAS) have identified potential genetic variants associated with the risk of major depressive disorder (MDD), but the underlying biological interpretation remains largely unknown. We aimed to prioritize genes that were pleiotropically or potentially causally associated with MDD. We applied the summary data-based Mendelian randomization (SMR) method integrating GWAS and gene expression quantitative trait loci (eQTL) data in 13 brain regions to identify genes that were pleiotropically associated with MDD. In addition, we repeated the analysis by using the meta-analyzed version of the eQTL summary data in the brain (brain-eMeta). We identified multiple significant genes across different brain regions that may be involved in the pathogenesis of MDD. The prime-specific gene BTN3A2 (corresponding probe: ENSG00000186470.9) was the top hit showing pleiotropic association with MDD in 9 of the 13 brain regions and in brain-eMeta, after correction for multiple testing. Many of the identified genes are located in the human major histocompatibility complex (MHC) region on chromosome 6 and are mainly involved in the immune response. Our SMR analysis indicated that multiple genes showed pleiotropic association with MDD across the brain regions. These findings provided important leads to a better understanding of the mechanism of MDD and revealed potential therapeutic targets for the prevention and effective treatment of MDD.

Mendelian randomization integrating GWAS and mQTL data identified novel pleiotropic DNA methylation loci for neuropathology of Alzheimer's disease.

The pathogenesis of Alzheimer's disease (AD) remains largely unclear. Exploring the genetic/epigenetic loci showing pleiotropic association with the neuropathologies of AD may greatly enhance understanding of the mechanisms underlying the development of AD. In this study, using data from the Religious Orders Study and the Rush Memory and Aging Project, we undertook a Mendelian randomization approach integrating genome-wide association studies (GWASs) and DNA methylation quantitative trait locus data to explore pleiotropic epigenetic loci for AD neuropathologies, including amyloid-ß (Aß) load and tau-containing neurofibrillary tangle density. We performed GWASs of DNA methylation in brain tissues from 592 participants and mapped 60,595 cis-SNP-CpG pairs after correction for multiple testing. By linking cis-DNA methylation quantitative trait locus with GWAS results for Aß load and tau tangles, we identified 47 CpGs showing pleiotropic association with Aß load by the Mendelian randomization analysis. We then used gene expression data from 537 individuals and performed quantitative trait methylation analysis. We found that 18 of the 47 CpGs were in cis associated with 25 mRNAs/genes, comprising 41 unique CpG-mRNA/gene pairs. Our findings shed light on the role of DNA methylation in the pathogenesis of Aß.

Association of genetic variants in and promoter hypermethylation of CDH1 with gastric cancer: a meta-analysis.

Gastric cancer (GC) is a common cause of cancer-related death. The etiology and pathogenesis of GC remain unclear, with genetic and epigenetic factors playing an important role. Previous studies investigated the association of GC with many genetic variants in and promoter hypermethylation of E-cadherin gene (CDH1), with conflicting results reported.To clarify this inconsistency, we conducted updated meta-analyses to assess the association of genetic variants in and the promoter hypermethylation of CDH1 with GC, including C-160A (rs16260) and other less-studied genetic variants,Data sources were PubMed, Cochrane Library, Google Scholar, Web of Knowledge, and HuGE, a navigator for human genome epidemiology.Study eligibility criteria and participant details are as follows: studies were conducted on human subjects; outcomes of interest include GC; report of genotype data of individual genetic variants in (or methylation status of) CDH1 in participants with and without GC (or providing odds ratios [OR] and their variances).Study appraisal and synthesis methods included the use of OR as a measure of the association, calculated from random effects models in meta-analyses. We used I for the assessment of between-study heterogeneity, and publication bias was assessed using funnel plot and Egger test.A total of 33 studies from 30 published articles met the eligibility criteria and were included in our analyses. We found no association between C-160A and GC (OR = 0.88; 95% confidence interval [CI], 0.71-1.08; P = 0.215), assuming an additive model (reference allele C). C-160A was associated with cardia (OR = 0.21; 95% CI, 0.11-0.41; P = 2.60 × 10), intestinal (OR = 0.66; 95% CI, 0.49-0.90; P = 0.008), and diffuse GC (OR = 0.57; 95% CI, 0.40-0.82; P = 0.002). The association of C-160A with noncardia GC is of bottom line significance (OR = 0.65; 95% CI, 0.42-1.01; P = 0.054). Multiple other less-studied genetic variants in CDH1 also exhibited association with GC. Gene-based analysis indicated a significant cumulative association of genetic variants in CDH1 with GC (all Ps <10). Sensitivity analysis excluding studies not meeting Hardy-Weinberg equilibrium (HWE) yielded similar results. Analysis by ethnic groups revealed significant association of C-160A with cardia GC in both Asian and whites, significant association with noncardia GC only in Asians, and no significant association with intestinal GC in both ethnic groups. There was significant association of C160-A with diffuse GC in Asians (P = 0.011) but not in whites (P = 0.081). However, after excluding studies that violate HWE, this observed association is no longer significant (P = 0.126). We observed strong association of promoter hypermethylation of CDH1 with GC (OR = 12.23; 95% CI, 8.80-17.00; P = 1.42 × 10), suggesting that epigenetic regulation of CDH1 could play a critical role in the etiology of GC.Limitations of this study are as follows: we could not adjust for confounding factors; some meta-analyses were based on a small number of studies; sensitivity analysis was limited due to unavailability of data; we could not test publication bias for some meta-analyses due to small number of included studies.We found no significant association of the widely studied genetic variant C-160A, but identified some other genetic variants showing significant association with GC. Future studies with large sample sizes that control for confounding risk factors and/or intensively interrogate CpG sites in CDH1 are needed to validate the results found in this study and to explore additional epigenetic loci that affect GC risk.

Effect of breastfeeding on childhood BMI and obesity: the China Family Panel Studies.

The objective of this study is to investigate the effect of breastfeeding on childhood obesity in China.We used data collected from the China Family Panel Studies, an ongoing, prospective, and nationwide longitudinal study to explore the extensive and dynamic social changes in China. A total of 7967 children were included in the analysis. Duration of breastfeeding was first treated as a continuous variable and subsequently dichotomized into ever versus never, ≥6 months versus <6 months, ≥8 months versus < 8 months, and ≥12 months versus <12 months. Multiple imputation was conducted and regressions with propensity score matching were performed. We also performed quantile regression to examine whether breastfeeding has an effect on childhood obesity among children with a specific quantile of body mass index (BMI).Consistent with findings from recent studies, in both adjusted and adjusted regressions, we did not find any statistically significant effect of breastfeeding on reducing the risk of obesity (unadjusted odds ratio, OR = 1.02, 95% confidence interval, CI 0.99, 1.05, P = 0.12; adjusted OR 1.01, 95% CI 0.98, 1.05, P = 0.36) or excessive weight (unadjusted OR = 1.01, 95% CI 0.99, 1.03, P = 0.26; adjusted OR = 1.00, 95% CI 0.98, 1.02, P = 0.90). Results were similar using various dichotomization of duration of breastfeeding. Quantile regression revealed that longer duration of breastfeeding is associated with higher BMI among children with small to medium quantile of BMI.Our findings echo recent research and caution against any population-wide strategy in attempting to reduce overweight and obesity through promotion of breastfeeding.