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Aim: To investigate the linkage of matrix metalloproteinase (MMP) gene polymorphisms with the pathogenesis of knee osteoarthritis (OA). Methods: This meta‐analysis study systematically retrieved relevant studies from PubMed, Embase, the Cochrane Central, Wanfang Data, CNKI, and SinoMed up to November 2020. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the association between MMP gene polymorphisms and OA. Results: A total of nine case–control studies comprising 1719 knee OA patients and 1904 controls were included in this meta‐analysis. The results revealed that MMP‐1‐1607 (rs1799750) 1G/2G polymorphism was not significantly associated with knee OA risk in four genetic models (OR (95% CI): allele model: 0.89 (0.57, 1.40), p =.615); dominant mode: 0.82 (0.47, 1.44), p =.486; recessive model: 0.88 (0.49, 1.57), p =.659; homozygote model: 0.79 (0.34, 1.82), p =.576. The association was significant for dominant model of MMP‐3 C/T: 1.54 (1.10–2.15), p =.013, especially in Asian ethnicity (1.63 (1.11, 2.39), p =.013). Variants of MMP‐13 C/T polymorphism were associated with increased risk of knee OA development based on dominant model: 1.56 (1.19, 2.06), p =.001 and homozygote model: 2.12 (1.44, 3.13), p <.001, and there were significant associations between MMP‐13 C/T polymorphism and knee OA risk in Asian ethnicity under different genetic models (all p >.05). Conclusions: Present evidence suggested that the gene polymorphisms of MMP‐1‐1607 1G/2G may not be associated with the risk of OA. But, the dominant model of MMP‐3 and MMP‐13 polymorphisms in Asian ethnicity was significantly correlated with knee OA. [ABSTRACT FROM AUTHOR]

Background: Recent resting-state functional magnetic resonance imaging studies have provided strong evidence of abnormal regional spontaneous brain activities among anxiety-disordered patients. However, the evidence has been divergent and inconclusive. Therefore, it is necessary to perform a meta-analysis identifying a common pattern of altered regional spontaneous brain activity for anxiety disorders.Method: Corresponding research of anxiety disorders, namely, whole-brain rs-fMRI studies that measured differences in regional homogeneity, amplitude of low-frequency fluctuations, or fractional amplitude of low-frequency fluctuations, were analyzed in this study. Overall, seven studies with 235 anxiety-disordered patients and 241 healthy controls were ultimately included in the meta-analysis. The meta-analysis was processed by seed-based d mapping.Results: Compared with healthy controls, patients with anxiety disorders showed significantly decreased regional spontaneous brain activities in the right putamen, the right orbital inferior frontal gyrus, and the right temporal pole. No increases in regional spontaneous brain activities were detected in patients relative to the controls.Limitation: Limited number of available studies, only Asian samples, and insufficient information of sample characteristics.Conclusion: The present study suggests that anxiety disorders are associated with aberrant regional brain activity in areas connected with emotion processing, which extends our understanding of anxiety disorders' pathophysiology. [ABSTRACT FROM AUTHOR]

• We have 15 publications with 5,740 cases and 9,931 controls were included in this meta-analysis. • We found that the T allele of the X -ray cross-complementing group 3 protein (XRCC3) Thr241Met polymorphism was significantly associated with an increased risk to gynecological malignancies (GM) in Asians but not in Caucasians. • Our findings indicate that the effect of the XRCC3 Thr241Met polymorphism on the risk of GM is ethnically different and this SNP has its obvious effect on the development of GM in Asians. • There was no meta-analysis about the association between XRCC3 Thr241Met polymorphism and risk of GM until now. Studies have investigated the relationship between the X -ray cross- complementing group 3 (XRCC3) Thr241Met polymorphism and the risk of gynecological malignancies (GM) with the contradictory conclusions. Here, a meta-analysis was performed to provide clear picture of the association between Thr241Met and GM risk. The Pubmed and Chinese National Knowledge Infrastructure (CNKI) databases were searched for published eligible studies. The pooled odds ratios (OR) with their corresponding 95% confidence interval (CI) was used to assessed the strength of association. Totally, 15 publications with 5,740 cases and 9,931 controls were included. In the overall analysis, the results of meta-analysis showed no significant association between the Thr241Met and the risk of GM. However, in the Asians subgroup, significant increased risks were found in the comparisons of TT/CT+TT vs. CC(TT vs. CC: OR=3.25, 95% CI=1.47–7.18; CT+TT vs. CC: OR=1.51, 95%CI=1.10–2.09) in Asians; additionally, stratified analysis by cancer type in Asians, significantly increased risks was found in cervical carcinoma (CT vs. CC: OR=1.50, 95%CI=1.04–2.14; TT vs. CC: OR=3.14, 95%CI=1.38–7.14; CT+TT vs. CC: OR=1.64, 95% CI=1.17–2.31). It suggests that the risk of GM might be significantly increased by the XRCC3 Thr241Met polymorphism according to ethnicity and cancer types. Further studies with larger sample size in different ethnic populations and different sites of GM are needed to verify the findings. [ABSTRACT FROM AUTHOR]

Purpose: Direct randomized comparisons of regorafenib, TAS-102, and fruquintinib for treating metastatic colorectal cancer (mCRC) are lacking. Here, we evaluated the efficacy and safety of three agents by a systematic review and a network meta-analysis. Methods: We included phase III randomized controlled trials in the PubMed, Embase, and Scopus Cochrane databases and ClinicalTrials.gov registry from initiation until January 2019. Data from randomized controlled trials including overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were extracted. Direct meta-analysis and indirect meta-analysis using network meta-analysis were assessed. Results: Five trials comprising a total of 2586 patients were included. For efficacy analysis of OS, no statistically significant differences were observed between regorafenib and TAS-102 (HR 0.945, 95% CI [0.677, 1.320], P = 0.753), regorafenib and fruquintinib (HR 1.056, 95% CI [0.690, 1.621], P = 0.814), or TAS-102 and fruquintinib (HR 1.117, 95% CI [0.740, 1.685], P = 0.610). However, fruquintinib was superior in PFS compared with TAS-102 (HR 1.756, 95% CI [1.079, 2.857], P = 0.023). Regorafenib and TAS-102 appeared to have a similar effect on PFS (HR 0.907, 95% CI [0.611, 1.346], P = 0.641), as did regorafenib and fruquintinib (HR 1.592, 95% CI [0.968, 2.618], P = 0.067). None of the three agents were better in terms of all grade AEs or any grade of 3–5 AEs. However, subgroup analysis of AEs exhibited different toxicity profiles between the three drugs. Conclusions: Indirect comparison suggested that the three agents had similar OS but that fruquintinib was superior in terms of PFS compared with that of TAS-102. These three agents had different toxicity profiles. [ABSTRACT FROM AUTHOR]

With the extensive application of titanium dioxide nanoparticles (TiO2 NPs), their impacts on calcium homeostasis have aroused extensive attention from scholars. However, there are still some controversies in relevant reports. Therefore, a systematic review was performed followed by a meta-analysis to explore whether TiO2 NPs could induce the imbalance in calcium homeostasis in vivo and in vitro through Revman5.4 and Stata15.0 in this research. Fourteen studies were included through detailed database retrieval and literature screening. Results indicated that the calcium levels were significantly increased and the activity of Ca2+-ATPase was significantly decreased by TiO2 NPs in vivo and in vitro. Subgroup analysis of the studies in vivo showed that TiO2 NPs exposure caused a significant increase in calcium levels in rats, exposure to large-sized TiO2 NPs (>10 nm) and long-term (>30 days) exposure could significantly increase calcium levels, and the activity of Ca2+-ATPase showed a concentration-dependent downward trend. Subgroup analysis of the studies in vitro revealed that intracellular calcium levels increased significantly in animal cells, exposure to small-sized TiO2 NPs (≤10 nm) and high concentration (>10 μg/mL) exposure could induce a significant increase in Ca2+ concentration, and the activity of Ca2+-ATPase also showed a concentration-dependent downward trend. This research showed that the physicochemical properties of TiO2 NPs and the experimental scheme could affect calcium homeostasis [ABSTRACT FROM AUTHOR]

Background and aims: The association between glutathione-S-transferase P1 (GSTP1) Ile105Val polymorphism and oxaliplatin-induced neuropathy has been investigated in a number of published studies. However, most of these studies were based on small sample sizes and the results remained inconsistent. To assess the relationship between GSTP1 gene Ile105Val polymorphism and its susceptibility to oxaliplatin-induced neuropathy, a meta-analysis of previous studies was conducted. Methods: Two investigators independently searched studies published up to December 2012 from the databases of PubMed, EMBASE and The Cochrane Library. The pooled effect was calculated as odds ratio (OR) and corresponding 95 % confidence intervals (CIs) using fixed-effect or random-effect model. Results: Twelve prospective trials and two retrospective clinical trials involving 2,191 participants met the inclusion criteria. Combined analyses of these studies showed no significant associations between GSTP1 Ile105Val polymorphism and oxaliplatin-induced neuropathy, yielding OR of 1.08 (95 %CI 0.67-1.74, P = 0.754) in dominant model. Similar results were also obtained in recessive model (OR = 1.67, 95 %CI 0.56-4.93, P = 0.357) and allelic analysis (OR = 1.22, 95 %CI 0.67-2.24, P = 0.513). Since significant heterogeneity across studies, the pooled effects were calculated by random-effect model. No evidence of publication biases was identified in this meta-analysis. Conclusion: This meta-analysis did not support the hypothesis that GSTP1 Ile105Val polymorphism was related to the occurrence of neurotoxicity in oxaliplatin-treated patients. Given the limited number of studies and potential bias, large-scale and well-designed clinical trials should be needed to confirm these hypotheses. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Inverse association was reported between omega-3 fatty acids (FAs) supplementation and the risk of cardiovascular disease. Identifying the effect of omega-3 FAs on endothelial function may contribute to explain the association. We conducted a meta-analysis to assess the effect of omega-3 FAs supplementation on endothelial function, as measured by flow-mediated dilation (FMD) and endothelium-independent vasodilation (EIV). Methods: Randomized placebo-controlled trials (RCTs) were identified from the databases of PubMed, EMBASE and Cochrane library by two investigators and the pooled effects were measured by weighted mean difference (WMD), together with 95% confidence intervals (CIs). Subgroup and meta-regression analyses were used to explore the source of between-study heterogeneity. Results: Totally 16 eligible studies involving 901 participants were finally included in meta-analysis. Compared with placebo, omega-3 FAs supplementation significantly increased FMD by 2.30% (95% CI: 0.89–3.72%, P =0.001), at a dose ranging from 0.45 to 4.5g/d over a median of 56days. Subgroup analyses suggested that the effect of omega-3 FAs on FMD might be modified by the health status of the participants or the dose of supplementation. Sensitivity analyses indicated that the protective effect of omega-3 on endothelial function was robust. No significant change in EIV was observed after omega-3 FAs supplementation (WMD: 0.57%; 95% CI: −0.88 to 2.01%; P =0.442). Conclusion: Supplementation of omega-3 fatty acids significantly improves the endothelial function without affecting endothelium-independent dilation. [Copyright &y& Elsevier]

Abstract: Introduction: Variants of PLA2G7 gene have been reported to be associated with coronary heart disease (CHD) since ten years ago, but the available data on this relationship are inconsistent. A meta-analysis was conducted to assess the effect of PLA2G7 gene on CHD. Materials and Methods: Association studies were identified from the databases of PubMed, EMbase, Chinese National Knowledge Infrastructure (CNKI) and Wanfang by two investigators and pooled effects (odds ratio (OR), together with 95% confidence interval (CI)) were calculated. Results: 14 association studies focusing on three polymorphisms (A379V, V279F and R92H) in PLA2G7 gene and risk of CHD were included in meta-analysis, covering a total of 8,280 cases and 5,656 controls. Concerning R92H, a significantly increased CHD risk was observed in recessive model, with an OR of 1.31(1.02, 1.68). Nevertheless, combined analyses of studies of the A379V and V279F variants showed no significant overall association with CHD, yielding ORs of 0.99(0.85, 1.15) and 1.09(0.88, 1.35) in allelic analysis, with strong evidence of heterogeneity. Similar results were also obtained in dominant and recessive models. Conclusions: The results indicate 92H allele had probably increased the risk of CHD, while the hypothesized effects of A379V and V279F polymorphisms on CHD cannot be confirmed in present data. However, given the limited number of studies and the potential biases, the influence of these polymorphisms on CHD risk needs further investigation. [ABSTRACT FROM AUTHOR]

Background: Alcoholic beverages are consumed by humans for a variety of dietary, recreational, and other reasons. It is uncertain whether the drinking effect on risk of all-cause mortality is different between women and men. We conducted a meta-analysis to evaluate the effect of drinking on the risk of all-cause mortality in women compared with men. Methods: We selected cohort studies with measures of relative risk (RR) and 95% confidence interval (CI) for all-cause mortality for drinkers versus nondrinkers by sex. Sex-specific RR and 95% CI were used to estimate the female-to-male ratio of RR (RRR) and 95% CI. Pooled estimates of RRR across studies were obtained by the fixed-effects model or the random-effects model (if heterogeneity was detected). Second-order fractional polynomials and random effects meta-regression models were used for modeling the dose-risk relationship. Results: Twenty-four studies were considered eligible. A total of 2,424,964 participants (male: 1,473,899; female: 951,065) were enrolled and 123,878 deaths (male: 76,362; female: 47,516) were observed. Compared with nondrinkers, the pooled female-to-male RRR for drinkers was 1.07 (95% CI: 1.02, 1.12). Subgroup analyses showed that the increased risk among female drinkers appeared to be consistent. J-shaped dose-response relationship was confirmed between alcohol and all-cause mortality in men and women, respectively. Moreover, the female-to-male RRR of all-cause mortality were 1.52 (95% CI: 1.01, 2.29), 1.95 (95% CI: 1.08, 3.49), and 2.36 (95% CI: 1.15, 4.88), respectively, for those who consumed 75, 90, and 100 g/day of alcohol. Conclusions: Females had an increased risk for all-cause mortality conferred by drinking compared with males, especially in heavy drinkers. The present study suggested that female drinkers, particularly heavy drinkers, should moderate or completely reduce their level of consumption to have a health benefit. [ABSTRACT FROM AUTHOR]

Background and Aims: MET, the hepatocyte growth factor receptor, is a receptor tyrosine kinase overexpressed and activated in a subset of gastric cancer. Several studies investigated the relationship between MET amplification and expression with the clinical outcome in patients with gastric cancer, but yielded conflicting results. We performed a systematic review and meta-analysis to determine the influence of MET amplification and expression on prognosis in gastric cancer. Methods: MEDLINE and EMBASE were searched for studies that explored the association between MET amplification and expression with survival in patients with gastric cancer up to 1 April, 2013. Data of individual hazard ratios (HRs) and 95% confidence intervals (CIs) for meta-analyses were extracted from the publications and combined in pooled HRs. Results: Fourteen studies involving 2,258 patients with gastric cancer were included. It was suggested that MET overexpression had an unfavorable impact on survival of patients with gastric cancer, with HRs (95% CIs) of 2.57 (95% CI: 1.97–3.35) overall, 2.82 (95% CI: 1.86–4.27) among studies using amplification for measure scale of MET and 2.42 (95% CI: 1.66–3.54) for expression. The magnitude of association was reduced whereas remained statistically significant in high quality studies or in larger sample size studies and corresponding HRs were 2.18(1.76, 2.70) and 2.35(1.93, 2.87), respectively, without significant heterogeneity. Conclusion: The findings from present study indicated that higher MET gene amplification and expression in gastric cancer was an indicator of poor prognosis. [ABSTRACT FROM AUTHOR]

Objective To determine whether thyroid antibodies are associated with an increased risk of gestational diabetes mellitus (GDM) in pregnant women. Design Meta-analysis. Setting Not applicable. Patient(s) Twenty cohort and case-control studies involving pregnant women with positive thyroid antibodies were the exposure of interest, and GDM was the outcome. Intervention(s) None. Main Outcome Measure(s) A fixed-effects model was used to evaluate the relationship between thyroid antibodies and the risk of GDM. Subgroup analyses were performed among different types of study design, different thyroid antibodies, and patients with specific thyroid dysfunction. Result(s) The search strategy identified 167 potentially relevant publications, of which 20 were included in the meta-analysis. A significant association between thyroid antibodies and GDM was observed. A meta-analysis of the 11 cohort studies with pregnant women with positive thyroid antibodies in their first trimester suggested no obvious risk of GDM compared with the reference group. In subgroup meta-analyses, no significant association between thyroid antibodies and GDM was found in euthyroid pregnant women, whereas a significant positive association was identified in women with a thyroid dysfunction. Conclusion(s) Based on the currently available evidence, there is a significant but not strong association between thyroid antibodies and the risk of GDM, and thyroid antibodies in the first trimester lack predictive value for the risk of GDM. In addition, thyroid antibodies may not increase the risk of GDM in euthyroid pregnant women. [ABSTRACT FROM AUTHOR]

Abstract: Background: Epidemiologic studies have reported conflicting results relating smoking to suicide risk. We conducted a meta-analysis of prospective cohort studies to evaluate the association of cigarette smoking with completed suicide. Methods: Eligible prospective cohort studies were identified from PubMed and EMbase databases (from 1966 to May 2011) and the reference lists of retrieved articles. Two authors independently extracted data and assessed study quality using the Newcastle–Ottawa Scale. Study-specific risk estimates were pooled using random-effects model and generalized least squares trend estimation was used to assess dose–response relationship. Results: Fifteen prospective cohort studies involving 2395 cases among 1,369,807 participants were included in the meta-analysis. Our data suggested that cigarette smoking significantly increased the risk of completed suicide. Compared with never smokers, the pooled RR was 1.28 (95% CI: 1.001–1.641) for former smokers, and 1.81 (95% CI: 1.50–2.19) for current smokers, respectively. Subgroup analyses showed that the increased suicide risk among current smokers appeared to be consistent, although there was heterogeneity among studies of current smoking (p < 0.001). Significant dose–response relationship was found between smoking and suicide, and the risk of suicide was increased by 24% for each increment of 10 cigarettes smoked per day (RR, 1.24; 95% CI: 1.20–1.28). Conclusions: Our meta-analysis robustly demonstrates that cigarette smoking is associated with an increased risk of completed suicide, consistent with a dose–response relationship. This conclusion has an important public health message for countries with high smoking prevalence and high suicide rate such as China. [Copyright &y& Elsevier]