Vascular smooth muscle cell (VSMC) apoptosis plays an important role in vascular remodeling and atherosclerotic plaque instability. Oxidative stress in diseased vessels promotes VSMC apoptosis in part by activating the c-Jun N-terminal kinase (JNK) pathway, which has been identified as a molecular target of miR-92a in macrophages. Here, we examined the expression and biological activity of miR-92a in VSMC. Quiescent VSMC exhibited a low basal expression of miR-92a, which was positively regulated by serum stimulation and negatively regulated by H2O2. Overexpression of miR-92a decreased H2O2-induced VSMC apoptosis as indicated by TUNEL assay and cleaved caspase-3 protein levels. Using 3′UTRreporter assay, we found that miR-92a overexpression led to suppression of both mitogen-activated protein kinase kinase 4 (MKK4)- and JNK1-dependent luciferase activity. We also found that 10 mer seed match between miRNA: mRNA pair is more efficient than 8 mer seed match for us to identify authentic miRNA target. Protein levels of active phospho-JNK and phospho-c-Jun, downstream targets of the MKK4–JNK1 pathway, were also decreased by overexpressing miR-92a in VSMC under oxidative stress. Consistent with these findings, overexpression of MKK4 reversed the anti-apoptotic effects of miR-92a in oxidatively stressed VSMC. In conclusion, miR-92a overexpression inhibits H2O2-induced VSMC apoptosis by directly targeting the MKK4–JNK1 pathway.

Background: The systemic use of corticosteroids for patients in severe community-acquired pneumonia (CAP) remains disputed in clinical practice. We undertook a systematic review and meta-analysis to assess the efficacy and safety of corticosteroids in patients with severe CAP. Methods: We searched MEDLINE (1946 to June 2018), EMBASE (1966 to June 2018), and the Cochrane Library database for randomized controlled trials (RCTs) conducted for severe CAP. The endpoints of the study included total mortality, length of intensive care unit (ICU) stay and mechanical ventilation. Results: Nine trials which contained 914 patients were included for final meta-analysis. Of the 488 patients in the corticosteroid group, there were 37 deaths (7.58%) and 56 deaths occurred in 426 patients in the control group (13.1%). Corticosteroid therapy was associated with a lower rate of all-cause mortality compared to control (odd ratio [OR] 0.63, 95% confidence interval [CI] 0.42–0.95, P = .03). Subgroup analysis was conducted to show that the drug type modified the effect of steroids for mortality rate: prednisolone or methylprednisolone therapy (OR 0.37, 95% CI 0.19–0.72) reduced total mortality, whereas hydrocortisone use did not (OR 0.90, 95% CI 0.54–1.49). We found the length of ICU stay was significantly shorter in the steroid group compared to control (MD −2.52 days, 95% CI −4.88 to −0.15; P = .04). And there was a reduction trend in the need for mechanical ventilation in corticosteroid group (OR 0.53, 95% CI 0.28–1.02; P = .06). There was no trend towards more adverse events in the corticosteroid arm compared to control (OR 0.92, 95% CI 0.58–1.47; P = .74). Conclusion: Overall, adjunctive systemic corticosteroids therapy was effective and safe for patients with severe CAP. In addition, the effects of mortality may differ according to the type of corticosteroids.

This study includes a retrospective analysis of the diagnosis and treatment of a case of severe pneumonia from fulminant psittacosis with multiple organ failure. Next-generation sequencing (NGS) of the pathogen was conducted. The purpose of this study was to summarize the clinical, laboratory, and imaging characteristics of the case and to improve understanding of the value of NGS in the diagnosis of severe community-acquired pneumonia (CAP). Fulminant psittacosis can be manifested as severe pneumonia with rapid progression, acute respiratory distress syndrome, sepsis, and multiple organ failure. Imaging shows unilateral lung consolidation, which is difficult to differentiate from CAP caused by common pathogens.The NGS technology can early detect rare pathogens, thus reducing unnecessary use of antibiotics and shortening the course of the disease.