OBJECTIVE To investigate the role of gonadotropin-releasing hormone (GnRH) in es-tradiol(E2 ) induced advance of puberty onset in rats. METHODS Postnatal day 18 SD rats were given a daily intragastric administration of corn oil or E2(50 μg.kg-1 ) for consecutive 5 d. The day of vaginal opening (VO), pathological changes in ovary and protein expression levels of GnRH, G protein-coupled receptor 54 ( GPR54) and phospholipase C ( PLC) in hypothalamus were observed. RESULTS As compared to corn oil controll group, VO was advanced by about 12.2 d, corpus luteum was observed in the ovary section, and the protein expression levels of GnRH,GPR54 and PLC in hypothalamus were significantly increased by 47%, 55% and 56% in E2 group, respectively. CONCLUSION E2 induced onset of puberty advance may be closely related to regulation of the expression of GnRH, GPR54 and PLC in hypothalamus.

The injury of vascular endothelial cell function is the beginning of the pathological process of atherosclerosis. Mitochondrial oxidative stress is closely related to vascular endothelial cell function, which causes the dysfunction of vascular endothelial cell by inducing mitophagy, reducing nitric oxide production, inflammation, cellular metabolic imbalance and apoptosis. Meanwhile, vascular endothelial cell could also maintain their homeostasis by regulating mitochondrial oxidative stress. The molecular signaling pathways of the vascular endothelial cell injury caused by mitochondrial oxidative stress in the pathological process of atherosclerosis were outlined in this review, which provided reference for further research on the molecular mechanism between mitochondrial oxidative stress and endothelial damage.

Objective:This study was performed to assess the effect of glycemic control on atrial fibrillation recurrence rates after heart surgery concomitant with Cox-Maze Ⅳ ablation.Methods:A retrospective analysis was performed on 317 diabetic patients with atrial fibrillation who underwent cardiac surgery combined with Cox-Maze Ⅳ ablation in our hospital from May 2016 to February 2020. The patients were followed up for(37.7±27.7) months, and the data of atrial fibrillation recurrence and clinical outcome were collected and compared. The limited cubic spline model was used to analyze the dose-relationship between HbA1c level and the recurrence of atrial fibrillation. The univariate and multivariate Cox proportional regression analysis was used to explore the risk factors of recurrent atrial fibrillation after Cox-Maze Ⅳ ablation. Results:Higher glycated hemoglobin(HbA1c) at the time of ablation was associated with higher post-ablation recurrence rates. The cumulative survival freedom from atrial fibrillation recurrence for patients with HbA1c ≥7.4% at time of operation at 12, 24, 36 and 48 months were 96.3%、75.8%、52.7% and 35.7%, respectively( P<0.001). Besides, the rates of all-cause mortality, cardiac mortality and rehospitalization were significantly lower in patients with HbA1c<7.4%(1.7% vs. 6.3%, P=0.03; 1.1% vs. 5.6%, P=0.02 and 5.7% vs. 20.4%, P=0.01). The multivariate Cox regression model showed that HbA1c was an independent risk factor for atrial fibrillation recurrence( P<0.05). Conclusion:Higher preoperative HbA1c levels were associated with increased recurrence of atrial fibrillation and adverse clinical outcomes in patients undergoing cardiac surgery combined with Cox-Maze Ⅳ ablation.

Novel therapies are urgently needed to improve global treatment of SARS-CoV-2 infection. Herein, we briefly provide a concise report on the medicinal chemistry strategies towards the development of effective SARS-CoV-2 inhibitors with representative examples in different strategies from the medicinal chemistry perspective.