Objective To develop a convenient nomogram for the bedside evaluation of patients with acute organophosphorus poisoning (AOPP). Design This was a retrospective study. Setting Two independent hospitals in northern China, the First Hospital of Jilin University and the Lequn Hospital of the First Hospital of Jilin University. Participants A total of 1657 consecutive patients admitted for the deliberate oral intake of AOPP within 24 hours from exposure and aged >18 years were enrolled between 1 January 2013 and 31 December 2018. The exclusion criteria were: normal range of plasma cholinesterase, exposure to any other type of poisonous drug(s), severe chronic comorbidities including symptomatic heart failure (New York Heart Association III or IV) or any other kidney, liver and pulmonary diseases. Eight hundred and thirty-four patients were included. Primary outcome measure The existence of severely poisoned cases, defined as patients with any of the following complications: cardiac arrest, respiratory failure requiring ventilator support, hypotension or in-hospital death. Results 440 patients from one hospital were included in the study to develop a nomogram of severe AOPP, whereas 394 patients from the other hospital were used for the validation. Associated risk factors were identified by multivariate logistic regression. The nomogram was validated by the area under the receiver operating characteristic curve (AUC). A nomogram was developed with age, white cells, albumin, cholinesterase, blood pH and lactic acid levels. The AUC was 0.875 (95% CI 0.837 to 0.913) and 0.855 (95% CI 0.81 to 0.9) in the derivation and validation cohorts, respectively. The calibration plot for the probability of severe AOPP showed an optimal agreement between the prediction by nomogram and actual observation in both derivation and validation cohorts. Conclusion A convenient severity evaluation nomogram for patients with AOPP was developed, which could be used by physicians in making clinical decisions and predicting patients’ prognosis.

Cardiopulmonary resuscitation and related life support technologies have improved substantially in recent years; however, mortality and disability rates from cardiac arrest (CA) remain high and are closely associated with the high incidence of cerebral ischemia-reperfusion injury (CIRI), which is explained by a "double-hit" model (i.e., resulting from both ischemia and reperfusion). Mitochondria are important power plants in the cell and participate in various biochemical processes, such as cell differentiation and signaling in eukaryotes. Various mitochondrial processes, including energy metabolism, calcium homeostasis, free radical production, and apoptosis, are involved in several important stages of the progression and development of CIRI. Mitophagy is a key mechanism of the endogenous removal of damaged mitochondria to maintain organelle function and is a critical target for CIRI treatment after CA. Mitophagy also plays an essential role in attenuating ischemia-reperfusion in other organs, particularly during post-cardiac arrest myocardial dysfunction. Regulation of mitophagy may influence necroptosis (a programmed cell death pathway), which is the main endpoint of organ ischemia-reperfusion injury. In this review, we summarize the main signaling pathways related to mitophagy and their associated regulatory proteins. New therapeutic methods and drugs targeting mitophagy in ischemia-reperfusion animal models are also discussed. In-depth studies of the mechanisms underlying the regulation of mitophagy will enhance our understanding of the damage and repair processes in CIRI after CA, thereby contributing to the development of new therapeutic strategies.

Cardiac arrest (CA) is a significant challenge for emergency physicians worldwide and leads to increased morbidity and mortality rates. The poor prognosis of CA primarily stems from the complexity and irreversibility of cerebral ischemia-reperfusion injury (CIRI). Ferroptosis, a form of programmed cell death characterized by iron overload and lipid peroxidation, plays a crucial role in the progression and treatment of CIRI. In this review, we highlight the mechanisms of ferroptosis within the context of CIRI, focusing on its role as a key contributor to neuronal damage and dysfunction post-CA. We explore the crucial involvement of the nuclear factor erythroid 2-related factor (Nrf2)-mediated signaling pathway in modulating ferroptosis-associated processes during CIRI. Through comprehensive analysis of the regulatory role of Nrf2 in the cellular responses to oxidative stress, we highlight its potential as a therapeutic target for mitigating ferroptotic cell death and improving the neurological prognosis of patients experiencing CA. Furthermore, we discuss interventions targeting the Kelch-like ECH-associated protein 1/Nrf2/antioxidant response element pathway, including the use of traditional Chinese medicine and Western medicine, which demonstrate potential for attenuating ferroptosis and preserving neuronal function in CIRI. Owing to the limitations in the safety, specificity, and effectiveness of Nrf2-targeted drugs, as well as the technical difficulties and ethical constraints in obtaining the results related to the brain pathological examination of patients, most of the studies focusing on Nrf2-related regulation of ferroptosis in CIRI are still in the basic research stage. Overall, this review aims to provide a comprehensive understanding of the mechanisms underlying ferroptosis in CIRI, offering insights into novel therapeutics aimed at enhancing the clinical outcomes of patients with CA.

Acute kidney injury (AKI) is a common clinical syndrome characterized by a rapid deterioration in renal function, manifested by a significant increase in creatinine and a sharp decrease in urine output. The incidence of morbidity and mortality associated with AKI is on the rise, with most patients progressing to chronic kidney disease or end-stage renal disease. Treatment options for patients with AKI remain limited. Circular RNA (circRNA) is a wide and diverse class of non-coding RNAs that are present in a variety of organisms and are involved in gene expression regulation. Studies have shown that circRNA acts as a competing RNA, is involved in disease occurrence and development, and has potential as a disease diagnostic and prognostic marker. CircRNA is involved in the regulation of important biological processes, including apoptosis, oxidative stress, and inflammation. This study reviews the current status and progress of circRNA research in the context of AKI.

Background: Neuronal ferroptosis is closely related to the disease of the nervous system, and the objective of the present study was to recognize and verify the potential ferroptosis-related genes to forecast the neurological outcome after cardiac arrest. Methods: Cardiac Arrest-related microarray datasets GSE29540 and GSE92696 were downloaded from GEO and batch normalization of the expression data was performed using “sva” of the R package. GSE29540 was analyzed to identify DEGs. Venn diagram was applied to recognize ferroptosis-related DEGs from the DEGs. Subsequently, The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed, and PPI network was applied to screen hub genes. Receiver operating characteristic (ROC) curves were adopted to determine the predictive value of the biomarkers, and the GSE92696 dataset was applied to further evaluate the diagnostic efficacy of the biomarkers. We explore transcription factors and miRNAs associated with hub genes. The “CIBERSORT” package of R was utilized to analyse the proportion infiltrating immune cells. Finally, validated by a series of experiments at the cellular level. Results: 112 overlapping ferroptosis-related DEGs were further obtained via intersecting these DEGs and ferroptosis-related genes. The GO and KEGG analysis demonstrate that ferroptosis-related DEGs are mainly involved in response to oxidative stress, ferroptosis, apoptosis, IL-17 signalling pathway, autophagy, toll-like receptor signalling pathway. The top 10 hub genes were selected, including HIF1A, MAPK3, PPARA, IL1B, PTGS2, RELA, TLR4, KEAP1, SREBF1, SIRT6. Only MAPK3 was upregulated in both GSE29540 and GAE92696. The AUC values of the MAPK3 are 0.654 and 0.850 in GSE29540 and GSE92696 respectively. The result of miRNAs associated with hub genes indicates that hsa-miR-214-3p and hsa-miR-483-5p can regulate the expression of MAPK3. MAPK3 was positively correlated with naive B cells, macrophages M0, activated dendritic cells and negatively correlated with activated CD4 memory T cells, CD8 T cells, and memory B cells. Compared to the OGD4/R24 group, the OGD4/R12 group had higher MAPK3 expression at both mRNA and protein levels and more severe ferroptosis. Conclusion: In summary, the MAPK3 ferroptosis-related gene could be used as a biomarker to predict the neurological outcome after cardiac arrest. Potential biological pathways provide novel insights into the pathogenesis of cardiac arrest.

Introduction: In-hospital CA (IHCA) is associated with rates of high incidence, low return of spontaneous circulation (ROSC), low survival to discharge, and poor neurological outcomes. We aimed to construct and evaluate prediction models for non-return of spontaneous circulation (non-ROSC) and poor neurological outcomes 12 months after ROSC (PNO-12).Methods: We retrospectively analyzed baseline and clinical data from patients experiencing cardiac arrest (CA) in a big academic hospital of Jilin University in China. Patients experiencing CA between September 1, 2019 and December 31, 2020 were categorized into the ROSC and non-ROSC groups. Patients maintaining ROSC >20 min were divided into the good and PNO-12 subgroups.Results: Univariate and multivariate logistic regression identified independent factors associated with non-ROSC and PNO-12. Two nomogram prediction models were constructed and evaluated. Of 2,129 patients with IHCA, 851 were included in the study. Multivariate logistic regression analysis revealed that male sex, age >80 years, CPR duration >23 min, and total dose of adrenaline >3 mg were significant risk factors for non-ROSC. Before CA, combined arrhythmia, initial defibrillation rhythm, and advanced airway management (mainly as endotracheal intubation) also influenced outcomes. The area under the receiver operating characteristic curve in the prediction model was 0.904 (C-index: 0.901). Respiratory failure, shock, CA in the monitoring area, advanced airway management, and noradrenaline administration were independent risk factors for PNO-12. The AUC was 0.912 (C-index: 0.918).Conclusions: Prediction models based on IHCA data could be helpful to reduce mortality rates and improve prognosis.