Research progress of effect of neutrophil elastase and its inhibitors in sepsis / 中华危重病急救医学

Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by infection. When an infection occurs, as the first line of defense of the body's immune system, neutrophils are first recruited to the site of infection to capture and kill pathogens by releasing neutrophil elastase (NE). However, a large amount of NE release will injury the surrounding normal tissues and induce organ dysfunction or failure. NE inhibitors can inhibit NE activity and reduce inflammatory response, which may be a promising drug for the treatment of sepsis. Currently, a variety of NE inhibitors have been developed and reported, but there is no systematic overview of their characteristics, and the role and underlying mechanisms of NE and related inhibitors in sepsis have not been thoroughly discussed. This article will make a review in this regard, in order to elucidate the effect of NE and its inhibitors in sepsis.

Research advances of myeloid-derived suppressor cells in sepsis-induced immunosuppression / 中华危重病急救医学

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Most patients with sepsis underwent a state of immune suppression after surviving the acute inflammatory response, and were susceptible to secondary nosocomial infections, leading to a prolonged hospitalization and increased mortality rate. Myeloid-derived suppressor cells (MDSCs), a heterogeneous population with immunosuppressive activities, can contribute to the development of immunosuppression in patients with cancer and inhibit the host immune response, but the characteristics of MDSCs and their functional mechanism has not been fully addressed in the development of sepsis-induced immunosuppression. Thus, this review will summary the new findings on the mechanisms of MDSCs in septic immunosuppressionin order to provide ideas and directions for targeting MDSCs as treatment of septic immunosuppression.

Plasma Metabolomic and Lipidomic Alterations Associated with COVID-19

The pandemic of the coronavirus disease 2019 (COVID-19) has become a global public health crisis. The symptoms of COVID-19 range from mild to severe conditions. However, the physiological changes associated with COVID-19 are barely understood. In this study, we performed targeted metabolomic and lipidomic analyses of plasma from a cohort of COVID-19 patients who had experienced different symptoms. We found the metabolite and lipid alterations exhibit apparent correlation with the course of disease in these COVID-19 patients, indicating that the development of COVID-19 affected whole-body metabolism of the patients. In particular, malic acid of the TCA cycle and carbamoyl phosphate of urea cycle reveal the altered energy metabolism and hepatic dysfunction, respectively. It should be noted that carbamoyl phosphate is profoundly down-regulated in fatal patients compared with mild patients. And more importantly, guanosine monophosphate (GMP), which is mediated by not only GMP synthase but also CD39 and CD73, is significant changed between healthy subjects and COVID-19 patients, as well as between the mild and fatal groups. In addition, the dyslipidaemia was observed in COVID-19 patients. Overall, the disturbed metabolic patterns have been found to align with the progress and severity of COVID-19. This work provides valuable knowledge about plasma biomarkers associated with COVID- 19 and potential therapeutic targets, as well as important resource for further studies of COVID-19 pathogenesis.

Protective effect of metoprolol on ischemia-reperfusion induced myocardial tissue injury in mice / 重庆医学

Objective To investigate the possible mechanism of metoprolol on protecting against ischemia‐reperfusion in‐duced injury .Methods A total of 32 healthy 3-4 months male C57BL/6 mice were divided into four groups(n=8)as following :Sham‐operating group(control group);metoprolol group;ischemia‐reperfusion group(I/R group);metoprolol + I/R group .Myo‐cardial injury ,apoptosis ,cytochrome c release ,Caspase‐3 activity and calpain activity were determined in these groups .Results Al‐though there was no obvious changes in the regions at risk between I/R group and metoprolol + I/R group ,metoprolol pretreat‐ment significantly reduced the ratio of the infarct to risk regions(P<0 .05) .In the I/R group ,the rate of cardiomyocyte apoptosis , cytochrome c release ,as well as the activity of Caspase‐3 and calpain significantly increased compared to the control group(P<0 .01) .However ,these effects of I/R injury were alleviated by pretreatment with metoprolol .Conclusion metoprolol might protect against ischemia‐reperfusion induced injury by preventing calpain activation .