Identifying key transcription factors and miRNAs coregulatory networks associated with immune infiltrations and drug interactions in idiopathic pulmonary arterial hypertension.

BACKGROUND: The deregulated genetic factors are critically associated with idiopathic pulmonary arterial hypertension (IPAH) development and progression. However, the identification of hub-transcription factors (TFs) and miRNA-hub-TFs co-regulatory network-mediated pathogenesis in IPAH remains lacking. METHODS: We used GSE48149, GSE113439, GSE117261, GSE33463, and GSE67597 for identifying key genes and miRNAs in IPAH. We used a series of bioinformatics approaches, including R packages, protein-protein interaction (PPI) network, and gene set enrichment analysis (GSEA) to identify the hub-TFs and miRNA-hub-TFs co-regulatory networks in IPAH. Also, we employed a molecular docking approach to evaluate the potential protein-drug interactions. RESULTS: We found that 14 TFs encoding genes, including ZNF83, STAT1, NFE2L3, and SMARCA2 are upregulated, and 47 TFs encoding genes, including NCOR2, FOXA2, NFE2, and IRF5 are downregulated in IPAH relative to the control. Then, we identified the differentially expressed 22 hub-TFs encoding genes, including four upregulated (STAT1, OPTN, STAT4, and SMARCA2) and 18 downregulated (such as NCOR2, IRF5, IRF2, MAFB, MAFG, and MAF) TFs encoding genes in IPAH. The deregulated hub-TFs regulate the immune system, cellular transcriptional signaling, and cell cycle regulatory pathways. Moreover, the identified differentially expressed miRNAs (DEmiRs) are involved in the co-regulatory network with hub-TFs. The six hub-TFs encoding genes, including STAT1, MAF, CEBPB, MAFB, NCOR2, and MAFG are consistently differentially expressed in the peripheral blood mononuclear cells of IPAH patients, and these hub-TFs showed significant diagnostic efficacy in distinguishing IPAH cases from the healthy individuals. Moreover, we revealed that the co-regulatory hub-TFs encoding genes are correlated with the infiltrations of various immune signatures, including CD4 regulatory T cells, immature B cells, macrophages, MDSCs, monocytes, Tfh cells, and Th1 cells. Finally, we discovered that the protein product of STAT1 and NCOR2 interacts with several drugs with appropriate binding affinity. CONCLUSIONS: The identification of hub-TFs and miRNA-hub-TFs co-regulatory networks may provide a new avenue into the mechanism of IPAH development and pathogenesis.

4-Phenylbutyric Acid Induces Protection against Pulmonary Arterial Hypertension in Rats.

BACKGROUND: Endoplasmic reticulum (ER) stress has been implicated in the pathophysiology of various pulmonary diseases via the activation of the unfolded protein response. However, the role of ER stress in pulmonary arterial hypertension (PAH) remains unclear. The well-known chemical chaperone 4-phenylbutyric acid (4-PBA) inhibits ER stress signaling. We hypothesized that known chemical chaperones, including 4-PBA, would inhibit the activation of ER stress and prevent and/or reverse PAH. METHODS AND RESULTS: Male Wistar rats were randomly divided into four groups: a normal control group (NORMAL group), a PAH group, and two PAH model plus 4-PBA treatment groups. The latter two groups included rats receiving 4-PBA by gavage each day as a preventive measure (the PRE group, with PBA starting on the day of PAH induction and continuing for 4 weeks) or as a reversal measure (the REV group, with PBA starting on the third week of PAH induction and continuing for 2 weeks). The PAH model was induced by intraperitoneally administering monocrotaline. The mean pulmonary artery pressure and mean right ventricular pressure were lower in the REV and PRE groups than in the NORMAL group. Furthermore, 4-PBA improved pulmonary arterial remodeling and suppressed the expression of ER stress indicators. CONCLUSION: Our findings indicate that PAH induces ER stress and provokes pulmonary arterial and right ventricular remodeling. Additionally, we show that attenuation of ER stress has the potential to be an effective therapeutic strategy for protecting pulmonary arteries.

Research on application of Chinese-Uyghur bilingual multimedia courseware in continuing medical education for Uygur rural physician in Xin Jiang / 中华医学科研管理杂志

Object Compare application of Han or Uyghur and Han-Uyghur bilingual multimedia courseware in continuing medical education for Uygur rural physicians.Methods 54 Uygur rural physicians who accepting continuing medical education were selected to be the study participants.We compared teaching effect between using Han or Uyghur and Han-Uyghur bilingual multimedia coursewares.Results Application of Han Uyghur bilingual multimedia courseware helped to improve learning interest 、confidence、reading ability and the comprehension of course;and improve examination score.Conclusion Application of Chinese-Uyghur bilingual multimedia courseware in continuing medical education for Uygur rural physician can result good learning effect,achieve the purpose of learn ing.

Research on Application of Evidence-based Medicine Education Pattern in the General Practitioners' Standardized Training / 中华医学科研管理杂志

Objective To compare the application of evidence-based medical education and traditional medical education in the general practitioners' standardized training.Methods 80 students accepting general practitioners' standardized training were researched to compare the teaching effect of evidence-based and traditional medical education.Results Application of evidence-based medical education help to improve learning interests and learning abilities subjectively,and it helps improve exam results objectively.Conclusions Application of evidence-based medical education in the general practitioners' standardized training receives good learning effect and can help achieve the learning goal.