Neutrophil extracellular traps (NETs) production is a major strategy employed by polymorphonuclear neutrophils (PMNs) to fight against microbes. NETs have been implicated in the pathogenesis of various lung injuries, although few studies have explored NETs in sepsis-associated acute lung injury (SI-ALI). Here, we demonstrate a major contribution of NETs to the pathology of sepsis-associated ALI by inducing ferroptosis of alveolar epithelial cells. Using both in vitro and in vivo studies, our findings show enhanced NETs accumulation in sepsis-associated ALI patients and mice, as well as the closely related upregulation of ferroptosis, the induction of which depends on METTL3-induced m6A modification of GPX4. Using a CLP-induced sepsis-associated ALI mouse model established with METTL3 -/- versus WT mice, in addition to METTL3 knockout and overexpression in vitro , we elucidated and confirmed the critical role of ferroptosis in NETs-induced ALI. These findings support a role for NETs-induced METTL3 modification and the subsequent induction of ferroptosis in the pathogenesis of sepsis-associated ALI.

Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable nonselective cation channel and can be activated during ischemia/reperfusion (I/R). This study tested whether blockade of TRPV4 can alleviate myocardial I/R injury in mice. TRPV4 expression began to increase at 1 h, reached statistically at 4 h, and peaked at 24–72 h. Treatment with the selective TRPV4 antagonist HC-067047 or TRPV4 knockout markedly ameliorated myocardial I/R injury as demonstrated by reduced infarct size, decreased troponin T levels and improved cardiac function at 24 h after reperfusion. Importantly, the therapeutic window for HC-067047 lasts for at least 12 h following reperfusion. Furthermore, treatment with HC-067047 reduced apoptosis, as evidenced by the decrease in TUNEL-positive myocytes, Bax/Bcl-2 ratio, and caspase-3 activation. Meanwhile, treatment with HC-067047 attenuated the decrease in the activation of reperfusion injury salvage kinase (RISK) pathway (phosphorylation of Akt, ERK1/2, and GSK-3β), while the activation of survival activating factor enhancement (SAFE) pathway (phosphorylation of STAT3) remained unchanged. In addition, the anti-apoptotic effects of HC-067047 were abolished by the RISK pathway inhibitors. We conclude that blockade of TRPV4 reduces apoptosis via the activation of RISK pathway, and therefore might be a promising strategy to prevent myocardial I/R injury.

After an initial demonstration of feasibility, this multicenter study shows that the J-Valve transcatheter heart valve system is a reasonable option for patients with predominant aortic regurgitation.

Delayed wound healing causes problems for many patients both physically and psychologically, contributing to pain, economic burden, loss of function, and even amputation. Although many factors affect the wound healing process, abnormally prolonged or augmented inflammation in the wound site is a common cause of poor wound healing. Excessive neutrophil extracellular trap (NET) formation during this phase may amplify inflammation and hinder wound healing. However, the roles of NETs in wound healing are still unclear. Herein, we briefly introduce NET formation and discuss the possible NET-related mechanisms in wound healing. We conclude with a discussion of current studies, focusing on the roles of NETs in diabetic and normoglycemic wounds and the effectiveness of NET-targeting treatments in wound healing.

The outbreak of a new coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) in China in December 2019 has brought serious challenges to disease prevention and public health. Patients with severe coronavirus disease 2019 (COVID-19) who undergo cardiovascular surgery necessitate extremely high demands from anesthesia personnel, and face high risks of mortality and morbidity. Based on the current understanding of COVID-19 and the clinical characteristics of cardiovascular surgical patients, the authors provide anesthesia management guidelines for cardiovascular surgery along with the prevention and control of COVID-19.

BackgroundPatients with sepsis may progress to acute respiratory distress syndrome (ARDS). Evidence of neutrophil extracellular traps (NETs) in sepsis-induced lung injury has been reported. However, the role of circulating NETs in the progression and thrombotic tendency of sepsis-induced lung injury remains elusive. The aim of this study was to investigate the role of tissue factor-enriched NETs in the progression and immunothrombosis of sepsis-induced lung injury.MethodsHuman blood samples and an animal model of sepsis-induced lung injury were used to detect and evaluate NET formation in ARDS patients. Immunofluorescence imaging, ELISA, Western blotting, and qPCR were performed to evaluate in vitro NET formation and tissue factor (TF) delivery ability. DNase, an anti-TF antibody, and thrombin inhibitors were applied to evaluate the contribution of thrombin to TF-enriched NET formation and the contribution of TF-enriched NETs to immunothrombosis in ARDS patients.ResultsSignificantly increased levels of TF-enriched NETs were observed in ARDS patients and mice. Blockade of NETs in ARDS mice alleviated disease progression, indicating a reduced lung wet/dry ratio and PaO2 level. In vitro data demonstrated that thrombin-activated platelets were responsible for increased NET formation and related TF exposure and subsequent immunothrombosis in ARDS patients.ConclusionThe interaction of thrombin-activated platelets with PMNs in ARDS patients results in local NET formation and delivery of active TF. The notion that NETs represent a mechanism by which PMNs release thrombogenic signals during thrombosis may offer novel therapeutic targets.

Our study demonstrated the feasibility of transapical implantation of the J-Valve system in high-risk patients with predominant aortic regurgitation.

Purpose This study aimed to evaluate effects of remote ischemic preconditioning (RIPC) on myocardial injury in patients undergoing off-pump coronary artery bypass graft surgery (OPCABG). Methods Sixty-five patients scheduled for the OPCABG were randomly assigned to control ( n = 32) or RIPC group ( n = 33). All patients received general anesthesia. Before the surgical incision, RIPC was induced on an upper limb with repeated 5-min ischemia and 5-min reperfusion for four times. Blood samples were collected from right internal jugular vein. Plasma levels of IL-6, IL-8, IL-10, TNF-α, cTnT, HFABP, IMA, and MDA were detected at pre-operatively and 0, 6, 18, 24, 48, 72, and 120 h after the surgery. Left internal mammary artery (LIMA) and great saphenous vein (GSV) was cut into 2–3 mm for Western blot analysis of Hif-1α. Results In the present study, RIPC treatment significantly reduced plasma levels of cardiac troponin T ( p < 0.05), heart-type fatty acid binding protein ( p < 0.05), ischemia modified albumin ( p < 0.05), malondialdehyde ( p < 0.05), as well as plasma levels of pro-inflammatory cytokines including IL-6, IL-8, and TNF-α ( P < 0.05, respectively). RIPC treatment significantly increased hypoxia-inducible factor-1α ( p < 0.05) expression as well. Mechanical ventilation time for postoperative patients was shortened in RIPC group than those in control group (17.4 ± 3.8 h vs. 19.7 ± 2.9 h, respectively, p < 0.05). Conclusion RIPC by upper limb ischemia shortens mechanical ventilation time in patients undergoing OPCABG. RIPC treatment reduces postoperative myocardial enzyme expression and pro-inflammatory cytokine production. RIPC is a protective therapeutic approach in the coronary artery bypass graft surgery.