Over the past few decades, mechanisms of programmed cell death have attracted the scientific community because they are involved in diverse human diseases. Initially, apoptosis was considered as a crucial mechanistic pathway for programmed cell death; recently, an alternative regulated mode of cell death was identified, mimicking the features of both apoptosis and necrosis. Several lines of evidence have revealed that dysregulation of necroptosis leads to pathological diseases such as cancer, cardiovascular, lung, renal, hepatic, neurodegenerative, and inflammatory diseases. Regulated forms of necrosis are executed by death receptor ligands through the activation of receptor-interacting protein kinase (RIPK)-1/3 and mixed-lineage kinase domain-like (MLKL), resulting in the formation of a necrosome complex. Many papers based on genetic and pharmacological studies have shown that RIPKs and MLKL are the key regulatory effectors during the progression of multiple pathological diseases. This review focused on illuminating the mechanisms underlying necroptosis, the functions of necroptosis-associated proteins, and their influences on disease progression. We also discuss numerous natural and chemical compounds and novel targeted therapies that elicit beneficial roles of necroptotic cell death in malignant cells to bypass apoptosis and drug resistance and to provide suggestions for further research in this field.

The aim of this study is to identify potential biomarkers for early diagnosis of gynecologic cancer in order to improve survival. Cervical cancer (CC) and endometrial cancer (EC) are the most common malignant tumors of gynecologic cancer among women in the world. As the underlying molecular mechanisms in both cervical and endometrial cancer remain unclear, a comprehensive and systematic bioinformatics analysis is required. In our study, gene expression profiles of GSE9750, GES7803, GES63514, GES17025, GES115810, and GES36389 downloaded from Gene Expression Omnibus (GEO) were utilized to analyze differential gene expression between cancer and normal tissues. A total of 78 differentially expressed genes (DEGs) common to CC and EC were identified to perform the functional enrichment analyses, including gene ontology and pathway analysis. KEGG pathway analysis of 78 DEGs indicated that three main types of pathway participate in the mechanism of gynecologic cancer such as drug metabolism, signal transduction, and tumorigenesis and development. Furthermore, 20 diagnostic signatures were confirmed using the least absolute shrink and selection operator (LASSO) regression with 10-fold cross validation. Finally, we used the GEPIA2 online tool to verify the expression of 20 genes selected by the LASSO regression model. Among them, the expression of PAMR1 and SLC24A3 in tumor tissues was downregulated significantly compared to the normal tissue, and found to be statistically significant in survival rates between the CC and EC of patients (p < 0.05). The two genes have their function: (1.) PAMR1 is a tumor suppressor gene, and many studies have proven that overexpression of the gene markedly suppresses cell growth, especially in breast cancer and polycystic ovary syndrome; (2.) SLC24A3 is a sodium–calcium regulator of cells, and high SLC24A3 levels are associated with poor prognosis. In our study, the gene signatures can be used to predict CC and EC prognosis, which could provide novel clinical evidence to serve as a potential biomarker for future diagnosis and treatment.

Objective To evaluate the use of N-acetylcysteine (NAC), a potent antioxidant, to prevent contrast-induced nephropathy (CIN). Methods We prospectively studied 209 patients (106 in the NAC group and 103 in the control group) who received contrast-enhanced computed tomography (CECT) in the emergency department (ED). The NAC group received intravenous NAC (600 mg) before CECT imaging to prevent CIN. Both the NAC and control groups were treated using a standardized hydration strategy, where clinically feasible. Results The patients' mean age was 79.6±9.8 years. The prevalence of hypertension, diabetes, and chronic kidney disease (CKD) were 63.2%, 27.3%, and 21.5%, respectively. The baseline clinical characteristics were similar between the two groups except for their body weight (p=0.011), amount of contrast material administered (p=0.049) and prevalence of CKD (p=0.002). The incidence of CIN was 7.5% in the NAC group and 14.6% in the control group. The adjusted odds ratio was 0.305 (95% confidence interval: 0.097 to 0.960, p=0.042). All-cause mortality was 7.5% in the NAC group and 12.6% in the control group, which was not significantly different. Temporary hemodialysis was required in 0% of subjects in the NAC group and 1.0% in the control group, which was not a statistically significant difference. Conclusion A single dose of NAC before CECT imaging can prevent CIN in an ED setting. However, it does not improve the mortality rate or the need for dialysis.

Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly performed as an adjunct to conventional cardiopulmonary resuscitation (CCPR) for refractory out-of-hospital cardiac arrest (OHCA). However, the specific benefits of ECPR concerning survival with favorable neurological outcomes remain uncertain. This study aimed to investigate the potential advantages of ECPR in the management of refractory OHCA. We conducted a retrospective cohort study involved OHCA patients between January 2016 and May 2021. Patients were categorized into ECPR or CCPR groups. The primary endpoint assessed was survival with favorable neurological outcomes, and the secondary outcome was survival rate. Multivariate logistic regression analyses, with and without 1:2 propensity score matching, were employed to assess ECPR’s effect. In total, 1193 patients were included: 85underwent ECPR, and 1108 received CCPR. Compared to the CCPR group, the ECPR group exhibited notably higher survival rate (29.4% vs. 2.4%; p < 0.001). The ECPR group also exhibited a higher proportion of survival with favorable neurological outcome than CCPR group (17.6% vs. 0.7%; p < 0.001). Multivariate logistic regression analysis demonstrated that ECPR correlated with increased odds of survival with favorable neurological outcome (adjusted odds ratio: 13.57; 95% confidence interval (CI) 4.60–40.06). Following propensity score matching, the ECPR group showed significantly elevated odds of survival with favorable neurological outcomes (adjusted odds ratio: 13.31; 95% CI 1.61–109.9). This study demonstrated that in comparison to CCPR, ECPR may provide survival benefit and increase the odds of favorable neurological outcomes in selected OHCA patients.