Histamine H2 receptor antagonist exposure was related to decreased all-cause mortality in critical ill patients with heart failure: a cohort study.

AIMS: Previous studies reported that histamine H2 receptor antagonists (H2RAs) had cardioprotective effects. However, the effect of H2RAs on mortality of critical ill patients with heart failure (HF) remains unclear. The aim of this study was to clarify the association between H2RAs and all-cause mortality of critical ill patients with HF based on Medical Information Mart for Intensive Care III database (MIMIC-III). METHODS AND RESULTS: Propensity score matching (PSM) was applied to account for the baseline differences between two groups that were exposed to H2RAs or not. The study primary outcome was all-cause mortality. Kaplan-Meier curves and multivariable Cox regression models were employed to estimate the effects of H2RAs on mortality of critical ill patients with HF. A total of 10 387 patients were included, involving 4440 H2RAs users and 5947 non-H2RAs users. After matching, 3130 pairs of patients were matched between H2RAs users and non-H2RAs users. The results showed significant association between H2RAs exposure and decreased 30-day, 90-day, and 1-year mortality in both univariate analyses and multivariate analyses [hazard ratio (HR) = 0.73, 95% confidence interval (CI): 0.65-0.83 for 30-day; HR = 0.80, 95%CI: 0.72-0.89 for 90-day; and HR = 0.83, 95%CI: 0.76-0.90 for 1-year mortality, respectively] by Cox regression after PSM. Furthermore, stratified analyses revealed that the 30-day, 90-day, and 1-year mortality of ranitidine users were significantly lower than those of famotidine users, respectively. CONCLUSION: Histamine H2 receptor antagonists exposure was associated with lower mortality in critical ill patients with HF. Furthermore, ranitidine might be superior to famotidine in reducing mortality of critical ill patients with HF.

Association between TNF-α gene polymorphisms and susceptibility of myelodysplastic syndromes: a meta-analysis.

OBJECTIVE: Myelodysplastic syndromes (MDS) constitute a heterogeneous group of clonal hematological diseases. Previous investigations reported that tumor necrosis factor-alpha (TNF-α) gene polymorphisms were associated with MDS susceptibility, but the results remained controversial. Thus, we conducted a meta-analysis to higher elucidate the correlation between TNF-α gene polymorphisms and MDS susceptibility. METHODS: The PubMed, Cochrane Library, Embase, Chinese National Knowledge Infrastructure (CNKI), and Wan Fang databases were searched for eligible literatures published up to July 2021. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were applied to evaluate the strength of association. RESULTS: Eight studies involving 1180 MDS patients and 1387 controls were included in this meta-analysis. For the TNF-α G308A polymorphism, we confirmed that the G allele (G versus A: P = 0.001), GG genotypes (GG versus GA: P = 0.005; GG versus GA + AA: P = 0.002), and GG + AA genotypes (GG + AA versus GA: P = 0.008) was significantly associated with decreased MDS susceptibility according to different genetic models. Furthermore, the G308A polymorphism was significantly correlated with decreased occurrence risk of MDS in the Caucasian population as compared with Asians in the above four genetic models (P < 0.05). However, no significant association was observed between the TNF-α G238A polymorphism and MDS risk. CONCLUSION: This research showed that TNF-α G308A polymorphism might be a potential biomarker in early clinical screening of MDS, which would contribute to improving the individualized prevention of MDS patients in clinic.

PARP1 as a prognostic biomarker for human cancers: a meta-analysis.

Aim: A comprehensive meta-analysis was carried out to evaluate the association between high PARP1 expression and clinical outcomes in diverse types of cancers. Materials & methods: The electronic databases for all articles about PARP1 expression and cancers were searched. Additionally, bioinformatics analysis was utilized to validate the results of the meta-analysis. Results: Fifty-two studies with a total of 7140 patients were included in the current meta-analysis. High PARP1 expression was found to be significantly associated with poor overall survival and recurrence in various cancers, which were further strengthened and complemented by the results of bioinformatic analysis. Furthermore, increased PAPR1 expression was also related to clinicopathological features. Conclusion: Our findings confirmed that PARP1 might be a promising biomarker for prognosis in human cancers.

Generation and identification of endothelial-specific Hrh2 knockout mice.

Histamine H2 receptor (HRH2) is closely associated with the development of cardiovascular and cerebrovascular diseases. However, systematic Hrh2 knockout mice did not exactly reflect the HRH2 function in specific cell or tissue types. To better understand the physiological and pathophysiological functions of endothelial HRH2, this study constructed a targeting vector that contained loxp sites flanking the ATG start codon located in Hrh2 exon 2 upstream and a neomycin (Neo) resistance gene flanked by self-deletion anchor sites within the mouse Hrh2 allele. The targeting vector was then electroporated into C57BL/6J embryonic stem (ES) cells, and positively targeted ES cell clones were micoinjected into C57BL/6J blastocysts, which were implanted into pseudopregnant females to obtain chimeric mice. The F1 generation of Hrh2flox/+ mice was generated via crossing chimeric mice with wild-type mice to excise Neo. We also successfully generated endothelial cell-specific knockout (ECKO) mice by crossing Hrh2flox/+ mice with Cdh5-Cre mice that specifically express Cre in endothelial cells and identified that Hrh2 deletion was only observed in endothelial cells. Hrh2flox/+ and Hrh2ECKO mice were normal, healthy and fertile and did not display any obvious abnormalities. These novel animal models will create new prospects for exploring roles of HRH2 during the development and treatment of related diseases.

Associations of methylenetetrahydrofolate reductase gene (MTHFR) rs1801131 and rs1801133 polymorphisms with susceptibility to vitiligo: A meta-analysis.

BACKGROUND: Vitiligo is a common pigmentary skin disorder, and genetic factors were acknowledged to be greatly associated with the pathogenesis of this disease. Recently, increasing studies investigated the associations of methylenetetrahydrofolate reductase (MTHFR) rs1801131 and rs1801133 polymorphisms with risks of vitiligo, but the results still remained controversial. AIM: The current meta-analysis was conducted to further evaluate the association of MTHFR polymorphisms with risk of vitiligo. METHODS: Eligible studies were searched in PubMed, EMBASE, Cochrane library, Chinese National Knowledge Infrastructure (CNKI), Technology of Chongqing (VIP), and Wan Fang Database until October 2020. All analyses were carried out using the Review Manager 5.3 software. RESULTS: A total of 6 studies that involved MTHFR rs1801131 and/or rs1801133 polymorphism were finally included, which enrolled 3599 participants. Our results showed that no correlations were found between MTHFR rs1801131, rs1801133 polymorphisms and vitiligo risks in overall group. However, subgroup analysis revealed that rs1801131 polymorphism was significantly associated with increased vitiligo risk in the allelic (C vs A: OR = 1.15, 95% CI = 1.02-1.29, P = .02) and homozygous models (CC vs AA: OR = 1.48, 95% CI = 1.10-2.01, P = .01) in Asian population and that the rs1801133 polymorphism was significantly associated with decreased vitiligo risk in the allelic model (T vs C: OR = 0.82, 95% CI = 0.74-0.92, P = .0005) also in Asian population. CONCLUSIONS: This meta-analysis confirmed the associations of MTHFR rs1801131 and rs1801133 polymorphisms with vitiligo risks and provided comprehensive insight into the pathogenesis of vitiligo.

Prognostic Value of Long Noncoding RNA SNHG12 in Various Carcinomas: A Meta-Analysis.

BACKGROUND: Numerous recent studies suggested that overexpression of the long noncoding RNA small nucleolar RNA host gene 12 (SNHG12) exhibited prooncogenic activity in multiple cancers. However, results regarding the prognostic value of SNHG12 in cancers still remained controversial. Therefore, we conducted a meta-analysis complemented with bioinformatics analysis to elucidate the clinical significance of SNHG12 in cancer patients. METHODS: PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, and Weipu databases were searched for eligible studies until July 2020. Additionally, bioinformatics analysis was applied to verify the results of meta-analysis. RESULTS: Twenty-three related studies consisting of 1389 cancer patients were enrolled in the current meta-analysis. Elevated SNHG12 expression was found to be significantly associated with poor overall survival (OS) (HR = 1.81; 95% CI: 1.53-2.13; P < 0.001) and disease-free survival (DFS) (HR = 1.40; 95% CI: 1.12-1.76; P = 0.004) in multiple cancers, which were also verified by the results of bioinformatics analysis. Moreover, overexpression of SNHG12 was also related to clinicopathological characteristics including LNM, distant metastasis, high clinical stage, large tumor size, and poor tumor differentiation in diverse types of cancers. CONCLUSION: The present findings indicated that SNHG12 might act as a novel biomarker for diagnosis or prognosis in human cancers.