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Background: Pulmonary arterial hypertension (PAH) is characterized by the apoptosis resistance and hyperproliferation of pulmonary artery smooth muscle cells (PASMCs). Its pathogenesis has not been revealed. Here, we carried out experiments to investigate the functions of miR‐140‐5p and tumor necrosis factor‐α (TNF‐α). Methods: We selected GSE703 from Gene Expression Omnibus (GEO) Database to conduct microarray analysis using R software and Gene Set Enrichment Analysis (GSEA). Combing bioinformatics results, the upregulation of miR‐140‐5p inhibited PAH progression through targeting TNF‐α. RNA expression was measured by quantitative real‐time polymerase chain reaction (RT‐qPCR) and protein level was measured by western blot analysis and enzyme‐linked immunosorbent assays (ELISA). We conducted monocrotaline (MCT) injection to rats to form PAH animal models. The lung tissues were observed by hematoxylin–eosin (HE) staining and Sirius red‐picric acid staining. Right ventricular systolic pressure (RVSP) and the ratio of right ventricle (RV)‐to‐left ventricle (LV) plus septum (S) weight (RV/[LV + S]) were measured in MCT‐induced animal models. Overexpression of miR‐140‐5p and TNF‐α were utilized to research the proliferation, migration, and phenotypic variation of hypoxia‐mediated PASMCs. The binding between miR‐140‐5p and TNF‐α 3′‐untranslated region (3′‐UTR) was confirmed via luciferase reporter assay. Results: Downregulation of miR‐140‐5p and upregulation of TNF‐α were observed in PAH rat model and hypoxia‐mediated PASMCs. And we proved that overexpression of miR‐140‐5p could suppress the proliferation, migration, and phenotypic variation of PASMCs, therefore inhibiting PAH pathogenesis. Luciferase assay verified that miR‐140‐5p targeted TNF‐α directly. A converse correlation was also shown between miR‐140‐5p and TNF‐α in PASMCs. Conclusions: miR‐140‐5p and TNF‐α are important regulators in PAH pathology and may serve as a therapeutic target for PAH. miR‐140‐5p might inhibit the occurrence and development of pulmonary arterial hypertension (PAH) by repressing tumor necrosis factor‐α (TNF‐α) expression via the TNF signaling pathway. These findings may help in the search of promising strategies for achieving better treatment outcome in patients diagnosed with PAH. [ABSTRACT FROM AUTHOR]

Purpose Statistical shrinkage is a potential statistical method to improve the accuracy of signal detection results and avoid spurious associations detected by disproportionality analyses. In this study, we introduced statistical shrinkage influence on disproportionality methods in spontaneous reporting system in China. Methods We added the shrinkage parameters in the numerator and denominator, denoted as in the formula of disproportionality analysis. The shrinkage parameters were subjectively set to between 0 and 5, with an interval of 0.1. Adverse drug reaction product label database was deemed as a proxy of golden standard to evaluate the effect of statistical shrinkage. Reports in the years of 2010-2011 were extracted from the national spontaneous reporting system database as the data source for analysis in this study. Results When α was around 0.5, the Youden index reached the maximum for each disproportionality methods in this study. The value of 0.6 was suggested as the most appropriate statistical shrinkage parameter for reporting odds ratio and proportional reporting ratio and 0.2 for information component based on the spontaneous reporting system of China. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]