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Emerging evidence has shown that leukocyte telomere length (LTL) is associated with various health-related outcomes, while the causality of these associations remains unclear. We performed a systematic review and meta-analysis of current evidence from Mendelian randomization (MR) studies on the association between LTL and health-related outcomes. We searched PubMed, Embase, and Web of Science up to April 2022 to identify eligible MR studies. We graded the evidence level of each MR association based on the results of the main analysis and four sensitive MR methods, MR-Egger, weighted median, MR-PRESSO, and multivariate MR. Meta-analyses of published MR studies were also performed. A total of 62 studies with 310 outcomes and 396 MR associations were included. Robust evidence level was observed for the association between longer LTL and increased risk of 24 neoplasms (the strongest magnitude for osteosarcoma, GBM, glioma, thyroid cancer, and non-GBM glioma), six genitourinary and digestive system outcomes of excessive or abnormal growth, hypertension, metabolic syndrome, multiple sclerosis, and clonal hematopoiesis of indeterminate potential. Robust inverse association was observed for coronary heart disease, chronic kidney disease, rheumatoid arthritis, juvenile idiopathic arthritis, idiopathic pulmonary fibrosis, and facial aging. Meta-analyses of MR studies suggested that genetically determined LTL was associated with 12 neoplasms and 9 nonneoplasm outcomes. Evidence from published MR studies supports that LTL plays a causal role in various neoplastic and nonneoplastic diseases. Further research is required to elucidate the underlying mechanisms and to bring insight into the potential prediction, prevention, and therapeutic applications of telomere length.

Pharmacological treatment of major depressive disorder is often inefficient, and multiple strategies are used for inadequate response to antidepressants. Second-generation antipsychotics are used as augmentation measures in clinical practice; evidence of their efficacy and acceptability is insufficient, and it remains confusing as to which drug should be selected first. In this systematic review and network meta-analysis, we included randomised controlled trials of second-generation antipsychotics used as adjunctive treatment in patients with suboptimal responses. Outcome measures were efficacy (response and remission) and acceptability (dropout due to any reason and adverse events). Thirty-three trials comprising 10 602 participants were included. Regarding efficacy, response rates indicated that all antipsychotics except for ziprasidone were more efficacious than the placebo, with the odds ratios (ORs) ranging from 1.34 for olanzapine and cariprazine [95% credible interval (CrI) 1.04–1.73 and 1.07–1.67, respectively] to 2.17 for risperidone (95% CrI 1.38–3.42). When considering remission, cariprazine was not effective (OR 1.21, 95% CrI 0.96–1.54). For acceptability, quetiapine (OR 0.68, 95% CrI 0.50–0.91), brexpiprazole (OR 0.69, 95% CrI 0.55–0.86), and cariprazine (OR 0.61, 95% CrI 0.46–0.82) were worse than the placebo. With regards to tolerability, only olanzapine (OR 0.51, 95% CrI 0.25–1.07) and risperidone (OR 0.48, 95% CrI 0.10–2.21) showed no significant differences compared with placebo. The administration of adjunctive antipsychotics is associated with high effectiveness and low acceptability. Risperidone and aripiprazole are more efficacious and accepted than other atypical antipsychotics.

No abstract

Background: With incidence of all types of cancers on the rise, cancer is now the leading cause of death worldwide. Previous studies have stressed the significant role of long non-coding RNAs (lncRNAs) in the diagnostic efficacy of cancer, onset and development. Method: A meta-analysis was implemented aiming to explore whether lncRNA, Metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), can work as a promising biomarker for prognosis in human cancers. Eligible articles were collected from multiple online databases (Pubmed, EMBASE, CNKI, Web of Science and Google Scholar) and meta-analysis was conducted to investigate the association between the expression levels of MALAT-1 and overall survival (OS), disease-free survival (DFS) or recurrence-free survival (RFS) and clinicopathological parameters which may have an impact on the pooled results. A total of 1389 patients from 13 studies were included in our meta-analysis, whose survival analysis was all univariate. Result: The results of our meta-analysis indicated that overexpression of MALAT-1 was significantly correlated with worse OS in cancer patients (HR = 1.941, 95% CI: 1.168-2.715, P<0.001) as well as worse DFS (HR = 2.20, 95% CI: 1.34-3.06, P < 0.001) and worse RFS (HR=1.90, 95% CI: 0.68-3.13, P < 0.001) in cancer patients in general. Due to heterogeneity may present in the overall results, subgroup analyses based on cancer type, cut-off value, patient size and median age were also performed in our study. In subgroups analysis, we found that the HR of group urinary system and group median age < 55 is particularly high compared with group OS (overall data). Conclusion: Tosum up, our meta-analysis results implied that increased expression level of MALAT-1 was positively associated with unfavorable prognostic results in many types of cancer patients. Besides, younger patients and patients with urinary tumors appear to be of poorer prognosis.