Huajun Xu

A systematic review and meta-analysis of the association between serotonergic gene polymorphisms and obstructive sleep apnea syndrome.

Background 5-Hydroxytryptamine receptor (5-HTR) and 5-hydroxytryptamine transporter (5-HTT) gene polymorphisms have been reported to be associated with susceptibility to obstructive sleep apnea syndrome (OSAS). The associations, derived from sporadic, inconsistent, small-sample-size studies, need to be evaluated further in a meta-analysis. Methods Relevant studies were identified by searching PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu. Eligible data were extracted from each included study. Odds ratios (ORs) were calculated using a fixed-effects or a random-effects model. The ORs and 95% confidence interval (CI) were used to assess the strength of the association between serotonergic gene polymorphisms and OSAS in the dominant and recessive models, as well as alleles. The Q statistic was used to evaluate homogeneity and Begg’s test was used to assess publication bias. Results Eight studies were finally included in the meta-analysis of the association between 5-HTR2A gene variants (including 102T/C and 1438G/A), 5-HTT gene polymorphisms (including 5-HTT gene-linked promoter region (5-HTTLRP), and serotonin transporter intron 2 variable number tandem repeat (STin2VNTR) and OSAS risk. The G allele of 5-HTR2A 1438G/A, long 5-HTTLPR, and 10-tandem-repeats STin2VNTR were shown to increase OSAS susceptibility, with ORs of 2.33 (A vs. G, 95% CI 1.48–3.66), 1.24 (L vs. S, 95% CI: 1.04–1.49), and 2.87 (10 vs. 12, 95% CI: 1.38–5.97), respectively. These significant differences were determined in both dominant and recessive models. Of the 5-HTR2A 1438G/A gene polymorphism, the AA genotype increased the OSAS risk, with an OR of 4.21 (95% CI: 2.83–6.25) in a recessive model in male OSAS patients, but no significant association was found in females. Conclusions Our meta-analysis demonstrated that polymorphisms in the 5-HTR2A 1438G/A and 5-HTT genes contributed to susceptibility to OSAS. The A allele of the 1438G/A gene polymorphism is predominantly distributed in males and increased the OSAS risk significantly.

Prognostic value of programmed cell death-ligand 1 expression in patients with non-small-cell lung cancer: evidence from an updated meta-analysis

Background The association between the expression of programmed cell death-ligand 1 (PD-L1) and survival in patients with non-small-cell lung cancer (NSCLC) is controversial. Thus, we conducted a meta-analysis of all available studies to evaluate the prognostic role of PD-L1 expression in NSCLC. Materials and methods PubMed, Embase, and Chinese (China National Knowledge Infrastructure and Wanfang) databases were searched to identify all eligible studies evaluating PD-L1 expression and the survival of NSCLC patients. Hazard ratios (HRs) and 95% confidence interval (CI) used to assess overall survival were extracted and pooled. Subgroup, sensitivity, and publication-bias analyses were also performed. Results Eleven articles reporting 12 studies that included a total of 1,653 patients met the inclusion criteria and were included in the meta-analysis. Higher PD-L1 expression did not correlate with prognosis in terms of overall survival in patients with NSCLC (HR =1.21, 95% CI: 0.85–1.71, P=0.29). However, a subgroup analysis showed a significant association between PD-L1 expression and poor prognosis in Chinese patients with NSCLC (HR =1.55, 95% CI: 1.04–2.29, P=0.03). The sensitivity analysis showed that the pooled results were not affected by the removal of any single study. There was also no significant publication bias. Conclusion Our meta-analysis indicated no statistically significant difference between PD-L1 expression and prognosis for patients with NSCLC. Additional, high-quality studies with larger sample sizes are needed to determine the prognostic value of PD-L1 expression in NSCLC.

Association between Self-Reported Habitual Snoring and Diabetes Mellitus: A Systemic Review and Meta-Analysis.

Aim. Several studies have reported an association between self-reported habitual snoring and diabetes mellitus (DM); however, the results are inconsistent. Methods. Electronic databases including PubMed and EMBASE were searched. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association between snoring and DM using a random-effects model. Heterogeneity, subgroup, and sensitivity analyses were also evaluated. Beggs, Eggers tests and funnel plots were used to evaluate publication bias. Results. A total of eight studies (six cross sectional and two prospective cohort studies) pooling 101,246 participants were included. Of the six cross sectional studies, the summary OR and 95% CI of DM in individuals that snore compared with nonsnorers were 1.37 (95% CI: 1.20–1.57, p < 0.001). There was no heterogeneity across the included studies (I 2 = 2.9%, p = 0.408). When stratified by gender, the pooled OR (95% CI) was 1.59 (1.20–2.11) in females (n = 12298), and 0.89 (0.65–1.22) in males (n = 4276). Of the two prospective studies, the pooled RR was 1.65 (95% CI, 1.30–2.08). Conclusions. Self-reported habitual snoring is statistically associated with DM in females, but not in males. This meta-analysis indicates a need to paying attention to the effect of snoring on the occurrence of DM in females.

Effect of CPAP on Endothelial Function in Subjects With Obstructive Sleep Apnea: A Meta-Analysis

Obstructive sleep apnea (OSA) is related to endothelial dysfunction. CPAP is the first-line treatment for OSA. We conducted a meta-analysis to evaluate the effect of CPAP on endothelial function in subjects with OSA. The PubMed, Embase, and Cochrane Library databases were searched. The overall effects were measured by the weighted mean difference with a 95% CI. Subgroup and meta-regression analyses were used to explore the sources of between-study heterogeneity. Eleven studies were eligible for the meta-analysis. A random-effects model revealed that CPAP significantly improved endothelial function as assessed by flow-mediated dilation (weighted mean difference of 2.92, 95% CI 2.21–3.63, P < .001), whereas there was no significant improvement in endothelial function in response to nitroglycerin-mediated dilation (weighted mean difference of 0.90, 95% CI −1.63 to 3.43, P = .48). Age, sex, CPAP compliance and duration, and sleep-related variables had no effect on reduction in arterial stiffness after CPAP. Sensitivity analyses indicated that the protective effect of CPAP on endothelial function was robust. CPAP significantly improved flow-mediated dilation in subjects with OSA. Long-term randomized controlled trials with larger sample sizes are needed to confirm the positive effect of CPAP on endothelial function in subjects with OSA.

Obstructive sleep apnea predicts risk of metabolic syndrome independently of obesity: a meta-analysis

Introduction Obstructive sleep apnea (OSA) has been suggested to be associated with a high risk of metabolic syndrome (MS). However, results on whether the association between OSA and risk of MS is independent of obesity, and the effect of nocturnal intermittent hypoxia (IH) on MS, are conflicting. Our purpose was to estimate the magnitude of the independent association between OSA and risk of MS and further explore whether nocturnal IH in OSA plays a role in MS risk. Material and methods The PubMed and EMBASE databases were systematically searched (until January 21, 2015) for available observational evidence. Unadjusted and body mass index (BMI)-adjusted pooled odds ratios (ORs) for MS in OSA or higher nocturnal IH were calculated using fixed or random models. Tests of homogeneity, publication bias, and robustness of the results were performed. Results A total of 13 independent studies (involving 857 participants in 3 case-control studies and 7077 participants in 10 cross-sectional studies) were included. The OSA was significantly associated with an increased risk of MS in a meta-analysis of 10 studies (pooled OR = 1.72, 95% CI: 1.31–2.26, p < 0.001), with a BMI-adjusted pooled OR of 1.97 (95% CI: 1.34–2.88, p < 0.001). Pooled results from 3 studies on the oxygen desaturation index (ODI) and MS risk (OR = 1.96, 95% CI: 1.73–2.22, p < 0.001) and 3 studies on the cumulative percentage of sleep time with SpO2 below 90% (CT90) and MS risk (OR = 1.05, 95% CI: 1.02–1.07, p < 0.001) were also significant. Conclusions Our findings demonstrated a significant association between OSA and increased MS risk independent of BMI, and further indicated a role of nocturnal IH in this association.

Metabolomics Profiling for Obstructive Sleep Apnea and Simple Snorers

Few clinical studies have explored altered urinary metabolite levels in patients with obstructive sleep apnea (OSA). Thus, we applied a metabolomics approach to analyze urinary metabolites in three groups of participants: patients with polysomnography (PSG)-confirmed OSA, simple snorers (SS), and normal subjects. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and gas chromatography coupled with time-of-flight mass spectrometry were used. A total of 21 and 31 metabolites were differentially expressed in the SS and OSA groups, respectively. Patients with OSA had 18 metabolites different from those with SS. Of the 56 metabolites detected among the 3 groups, 24 were consistently higher or lower. A receiver operator curve analysis revealed that the combination of 4-hydroxypentenoic acid, arabinose, glycochenodeoxycholate-3-sulfate, isoleucine, serine, and xanthine produced a moderate diagnostic score with a sensitivity (specificity) of 75% (78%) for distinguishing OSA from those without OSA. The combination of 4-hydroxypentenoic acid, 5-dihydrotestosterone sulfate, serine, spermine, and xanthine distinguished OSA from SS with a sensitivity of 85% and specificity of 80%. Multiple metabolites and metabolic pathways associated with SS and OSA were identified using the metabolomics approach, and the altered metabolite signatures could potentially serve as an alternative diagnostic method to PSG.

Effect of cyanotoxins on the hypothalamic-pituitary-gonadal axis in male adult mouse.

Background Microcystins LR (MC-LR) are hepatotoxic cyanotoxins that have been shown to induce reproductive toxicity, and Hypothalamic–Pituitary–Gonadal Axis (HPG) is responsible for the control of reproductive functions. However, few studies have been performed to evaluate the effects of MC-LR on HPG axis. This study aimed to investigate the MC-LR-induced toxicity in the reproductive system of mouse and focus on the HPG axis. Methods Adult male C57BL/6 mice were exposed to various concentrations of MC-LR (0, 3.75, 7.50, 15.00 and 30.00 µg/kg body weight per day) for 1 to 14 days, and it was found that exposure to different concentrations of MC-LR significantly disturbed sperm production in the mice testes in a dose- and time-dependent manner. To elucidate the associated possible mechanisms, the serum levels of testosterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were assessed. Meanwhile, PCR assays were employed to detect alterations in a series of genes involved in HPG axis, such as FSH, LH, gonadotropin-releasing hormone (GnRH) and their complement receptors. Furthermore, the effect of MC-LR on the viability and testosterone production of Leydig cells were tested in vitro. Results: MC-LR significantly impaired the spermatogenesis of mice possibly through the direct or indirect inhibition of GnRH synthesis at the hypothalamic level, which resulted in reduction of serum levels of LH that lead to suppression of testosterone production in the testis of mice. Conclusions MC-LR may be a GnRH toxin that would disrupt the reproductive system of mice.

Obstructive Sleep Apnea Susceptibility Genes in Chinese Population: A Field Synopsis and Meta-Analysis of Genetic Association Studies

Background Epidemiological studies to date have evaluated the association between genetic variants and the susceptibility to obstructive sleep apnea (OSA). However, the results of these studies have been inconclusive. In this current study we performed meta-analysis of genetic association studies (GAS) to pool OSA-susceptible genes in Chinese population, to perform a more precise evaluation of the association. Methods Various databases (i.e., PubMed, EMBASE, HuGE Navigator, Wanfang and CNKI) were searched to identify all eligible GAS-related variants associated with susceptibility to OSA. The generalized odds ratio metric (ORG) and the odds ratio (OR) of the allele contrast were used to quantify the impact of genetic variants on the risk of OSA. Cumulative and recursive cumulative meta-analyses (CMA) were also performed to investigate the trend and stability of effect sizes as evidence was accumulated. Results Thirty-two GAS evaluating 13 polymorphisms in 10 genes were included in our meta-analysis. Significant associations were derived for four polymorphisms either for the allele contrast or for the ORG. The variants TNF-α-308G/A, 5-HTTLPR, 5-HTTVNTR, and APOE showed marginal significance for ORG (95% confidence interval [CI]): 2.01(1.31–3.07); 1.31(1.09–1.58); 1.85(1.16–2.95); 1.79(1.10–2.92); and 1.79(1.10–2.92) respectively. In addition, the TNF-α-308G/A, 5-HTTLPR, and 5-HTTVNTR variants showed significance for the allele contrast: 2.15(1.39–3.31); 2.26(1.58–3.24); 1.32(1.12–1.55); and 1.86(1.12–3.08) respectively. CMA showed a trend towards an association, and recursive CMA indicated that more evidence was needed to determine whether this was significant. Conclusions TNF-α, 5-HTT, and APOE genes can all be proposed as OSA-susceptibility genes in Chinese population. Genome-wide association studies (GWAS) are therefore urgently needed to confirm our findings within a larger sample of OSA patients in China.

An updated meta-analysis of the association between tumor necrosis factor-α -308G/A polymorphism and obstructive sleep apnea-hypopnea syndrome.

Background Several studies have reported that the tumor necrosis factor-α (TNF-α) -308G/A polymorphism is associated with susceptibility to obstructive sleep apnea-hypopnea syndrome (OSAHS). However, these results are controversial and conflicting. Objective To evaluate the association between TNF-α-308G/A and OSAHS risk by meta-analysis. Methods Electronic databases, including PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu, were searched to identify relevant studies. Data were extracted from the included studies. A model-free approach using odds ratio (OR), generalized odds ratio (ORG) and 95% confidence interval (CI) of the allele contrast to assess the association between the -308G/A polymorphism and OSAHS risk. Cumulative and recursive cumulative meta-analyses (CMA) were also carried out to investigate the trend and stability of effect sizes as evidence accumulated. Results Seven studies including 1369 OSAHS patients and 1064 controls were identified in this meta-analysis. Significant associations were derived from the variants of the allele contrast [(OR, 1.78; 95% CI, 1.45–2.18) or (ORG, 2.01; 95% CI, 1.27–3.19). CMA showed a trend of an association. Recursive CMA indicated that more evidence is needed to conclude on the status of significance. No significant publication bias was found. Conclusions Our meta-analysis suggested that the TNF-α-308G/A polymorphism contribute to the risk of OSAHS. Further studies with larger sample should be performed to confirm our findings.

Changes in cerebral metabolites in obstructive sleep apnea: a systemic review and meta-analysis.

Cognitive impairment is associated with changes in cerebral metabolites in patients with obstructive sleep apnea (OSA). Several studies have used magnetic resonance spectroscopy (MRS) to detect variations in cerebral metabolites; however, the results have been inconsistent. This meta-analysis summarizes the differences in cerebral metabolites between patients with OSA and controls. Two electronic databases, PubMed and Embase, were searched for articles (published before March 31, 2016) describing studies that used MRS to evaluate the cerebral metabolite changes. The overall effects were measured using the weighted mean difference with a 95% confidence interval. Subgroup analysis and sensitivity analysis were used to explore the sources of between-study heterogeneity and the stability of the results. Publication bias was also evaluated. Thirteen studies were ultimately included. In the hippocampus, the N-acetylaspartate (NAA)/creatine ratio was lower in patients with OSA. In the frontal lobe, only the NAA/choline ratio was lower in patients with OSA. Cerebral metabolites are significantly altered in the hippocampus in patients with OSA. Further clinical studies are needed to explore the underlying mechanisms between OSA and the changes in cerebral metabolites in the brain.