Accumulating evidence indicates that programmed necrosis plays a critical role in cell death during ischemia-reperfusion. Necrostatin-1 (Nec-1), a small molecule capable of inhibiting a key regulator of programmed necrosis (RIP1), was shown to prevent necrotic cell death in experimental models including cardiac ischemia. However, no functional follow-up was performed and the action of Nec-1 remains unclear. Here, we studied whether Nec-1 inhibits RIP1-dependent necrosis and leads to long-term improvements after ischemia-reperfusion in vivo. Mice underwent 30 min of ischemia and received, 5 min before reperfusion, 3.3 mg/kg Nec-1 or vehicle treatment, followed by reperfusion. Nec-1 administration reduced infarct size to 26.3 ± 1.3% (P = 0.001) compared to 38.6 ± 1.7% in vehicle-treated animals. Furthermore, Nec-1 inhibited RIP1/RIP3 phosphorylation in vivo and significantly reduced necrotic cell death, while apoptotic cell death remained constant. By using MRI, cardiac dimensions and function were assessed before and 28 days after surgery. Nec-1-treated mice displayed less adverse remodeling (end-diastolic volume 63.5 ± 2.8 vs. 74.9 ± 2.8 μl, P = 0.031) and preserved cardiac performance (ejection fraction 45.81 ± 2.05 vs. 36.03 ± 2.37%, P = 0.016). Nec-1 treatment significantly reduced inflammatory influx, tumor necrosis factor-α mRNA levels and oxidative stress levels. Interestingly, this was accompanied by significant changes in the expression signature of oxidative stress genes. Administration of Nec-1 at the onset of reperfusion inhibits RIP1-dependent necrosis in vivo, leading to infarct size reduction and preservation of cardiac function. The cardioprotective effect of Nec-1 highlights the importance of necrotic cell death in the ischemic heart, thereby opening a new direction for therapy in patients with myocardial infarction.

Background: The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, Hubei province, has led to the quarantine of many residents in their homes, in order to mitigate its spread. Some of these people developed mental health problems, and many solutions have been put in place to address the mental health issues of patients and health professionals affected by the disease. However, not much attention has been given to students, particularly those from medical school. The present study aims to conduct an online survey to investigate the mental health status of students from a medical college in Hubei province. Materials and Methods: The WeChat-based survey program Questionnaire Star, which contained questions from Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), was utilized for the present study. Results: A total of 217 students participated in the survey. Among these students, 127 were female and 90 were male. Furthermore, 77 students (35.5%) who participated in the survey were in a state of depression, and 48 (22.1%) were in a state of anxiety. The majority of students who were in depressed (n=75) or anxiety (n=46) states had mild or moderate states. There were no significant differences in students in terms of gender, geographical location, and grade, for the prevalence of depression and anxiety. Conclusion: The present study implies that universities need to take measures to prevent, identify, and deal with mental health problems among students during large-scale stressors.