Myocardial infarction (MI) involves a pathological process in which its association with ferroptosis is notably pronounced, and targeted regulation of ferroptosis presents a promising approach for treating MI. This work delineates the molecular basis by which the natural sesquiterpene germacrone protects against cardiomyocyte ferroptosis following isoproterenol (ISO)-induced MI. We established a murine model of ISO-induced MI, paired with an injured H9c2 cardiomyocyte model in vitro. Mice in the experimental group received daily oral germacrone (25, 50, and 100 mg/kg) for 7 consecutive days. We profiled myocardial injury markers and key nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) axis proteins. The mechanism of action was confirmed by utilizing ML385, the Nrf2-specific inhibitor. Germacrone significantly reduced ISO-induced myocardial injury in mice, improving cardiac function and decreasing myocardial histopathological damage. Germacrone universally attenuated the elevation of myocardial injury and inflammatory markers in all experimental models. It also decreased the apoptosis rate of H9c2 cells. Germacrone inhibited myocardial ferroptosis and upregulated the abundance of pivotal regulatory proteins, including Nrf2, GPX4, and heme oxygenase-1 (HO-1), along with solute carrier family 7 member 11 (SLC7A11). ML385, an Nrf2 antagonist, can block germacrone's protective effect against ISO-induced myocardial ferroptosis and reverse its upregulation of these pathway proteins. These findings provide a new potential target and experimental foundation for MI treatment.

BACKGROUND:Cardiotoxin (CTX) from Naja atra venom is a principal virulence factor responsible for progressive local tissue necrosis and systemic inflammation following snakebite. Despite its clinical importance, the molecular mechanisms underlying CTX-induced skin injury remain poorly defined. METHODS:We employed a two-arm strategy combining transcriptome-guided discovery with mechanistic functional validation. In the transcriptomic arm, C57BL/6 mice received intradermal CTX injection (120 μg/50 μL), and skin tissues were harvested at 6, 12, and 24 h post-injection for RNA-seq analysis. Differentially expressed genes (DEGs) were screened and subjected to KEGG/GO enrichment and ssGSEA-based cell death mode scoring. In the functional validation arm, a separate cohort of mice was assessed at 72 h post-injection, with gross necrosis area quantified, followed by H&E staining, immunohistochemistry (IHC), and Western blot. In vitro validation was performed in human HaCaT keratinocytes using CCK-8 cytotoxicity assay, optical microscopy, transmission electron microscopy (TEM), propidium iodide/DAPI (PI/DAPI) dual staining, ROS detection, ELISA for IL-1β, LDH release assay, and pharmacological inhibition with MCC950 (NLRP3 inhibitor), VX-765 (caspase-1 inhibitor), and N-acetylcysteine (NAC, ROS scavenger). RESULTS:RNA-seq identified 2,490 DEGs (|log2FC| > 1, FDR < 0.01; 1,047 upregulated, 1,443 downregulated). KEGG enrichment revealed that the NOD-like receptor signaling pathway was the most significantly enriched pathway (enrichment fold = 6.8, p_adj < 0.001, with 42 differentially expressed genes annotated to this pathway). Among eight assessed cell death modalities, ssGSEA demonstrated that pyroptosis had the highest activation score (p < 0.05). Six canonical NLRP3/caspase-1/GSDMD pathway genes-Nlrp3, Pycard, Gsdmd, Il18, Nfkb, and Tlr4-were continuously upregulated from 6 to 24 h. Western blot confirmed both full-length GSDMD and its cleaved N-terminal fragment (GSDMD-N), along with NLRP3 inflammasome activation, in CTX-treated skin tissues and HaCaT cells. In vitro, CTX induced characteristic pyroptotic morphology and pyroptotic bodies (1-5 μm by TEM). Western blot confirmed NLRP3/GSDMD-N upregulation in HaCaT cells. CTX also induced dose-dependent intracellular ROS accumulation (DCFH-DA fluorescence). Importantly, all three inhibitors-NAC (ROS scavenger), MCC950 (NLRP3 inhibitor), and VX-765 (caspase-1 inhibitor)-significantly attenuated CTX-induced LDH release, IL-1β secretion, and GSDMD cleavage (all p < 0.0001), confirming the mechanistic hierarchy: ROS → NLRP3 → caspase-1 → GSDMD. CONCLUSION:CTX induces intracellular ROS accumulation that activates the NLRP3/caspase-1/GSDMD pyroptotic cascade as an important mechanism contributing to skin tissue necrosis through membrane pore formation and inflammatory amplification. Pharmacological inhibition (NAC, MCC950, VX-765) confirmed a hierarchical ROS → NLRP3 → caspase-1 → GSDMD cascade. The ROS-NLRP3-caspase-1-GSDMD axis constitutes a tractable therapeutic target for Naja atra envenomation.

Background: This study aims to develop a radiomics-driven machine learning model based on early brain CT features to predict neurological outcomes in patients undergoing ECPR and to investigate whether the integration of these radiomic features provides incremental predictive value beyond traditional clinical characteristics. Methods: We retrospectively analyzed 60 patients who underwent ECPR from January 2020 to September 2025. All patients underwent noncontrast brain CT within 24 h following ECPR. Neurological outcomes were assessed at hospital discharge using the CPC scale (1-2 favorable and 3-5 unfavorable), as long-term follow-up data were unavailable in this retrospective study. Radiomic features were extracted from the bilateral cortex, white matter, and caudate-putamen on early post-ECPR brain CT scans using the Harvard-Oxford atlas. Five machine learning models (LR, RF, KNN, SVM, and XGB) were developed for each region via nested cross-validation, and the best-performing cortical region was selected based on predictive performance. Stable radiomic features from the optimal region (selection frequency >= 60%) were then used to calculate a radiomic score (Rad-score) for each patient. Finally, a radiomic-enhanced model was constructed by integrating this Rad-score with clinical variables using logistic regression with LASSO feature selection within a nested cross-validation framework, and its performance was compared against a baseline clinical model. Results: Among the three brain regions evaluated, the cortex yielded the highest predictive performance for neurological outcomes. The radiomics-enhanced model demonstrated superior discriminative performance compared with the baseline clinical model (mean AUC: 0.804 vs. 0.648; Delta AUC = 0.156). Significant improvements in risk reclassification were observed (NRI = 0.344, 95% CI: 0.093-0.583, p = 0.006; IDI = 0.259, 95% CI: 0.115-0.388, p < 0.001), along with better calibration (Brier score: 0.1237 vs. 0.2025) and higher clinical net benefit (average improvement: 0.0962). SHAP analysis identified the Rad-score as the most influential predictor. Conclusion: Early head CT radiomic features, particularly those derived from the cerebral cortex, may serve as a potential predictor of neurological outcomes in ECPR patients. Compared with clinical features alone, the radiomics-enhanced model improves neurological outcome prediction, suggesting incremental prognostic value that could offer preliminary support for early clinical decision-making.

Early pulmonary abnormalities after freshwater drowning can be overinterpreted as bacterial pneumonia, especially when inflammatory biomarkers and respiratory microbiology are positive. A 20-year-old man was resuscitated after approximately 2 min of freshwater submersion. Day 1 chest CT showed bilateral lower-lobe-predominant opacities compatible with non-cardiogenic pulmonary oedema and aspiration-related lung injury, with near-complete resolution by Day 25. Day 3 bronchoscopy showed diffuse, non-removable, millet-seed-like whitish tracheal mucosal protrusions with hyperaemia and oedema, compatible with acute irritative airway injury. BALF mNGS detected multiple gram-negative bacterial signals, predominantly Klebsiella pneumoniae, while sputum culture yielded ESBL-negative, susceptible K. pneumoniae. Possible drowning-associated pneumonia was considered because of aspiration, fever, markedly elevated inflammatory biomarkers and concordant microbiology; however, rapid radiological improvement and clinical stability suggested a substantial non-infectious component. The patient recovered after an 8-day course of piperacillin-tazobactam without antibiotic escalation, corticosteroids, mechanical ventilation or acute respiratory distress syndrome.

Background:Sepsis is characterized by dysregulated inflammation, endothelial injury, platelet activation, and immunothrombosis. In patients with atrial fibrillation (AF), these processes may further increase thrombotic risk and worsen clinical outcomes. Aspirin may be relevant in this setting because of its antiplatelet and anti-inflammatory properties; however, evidence in sepsis patients with AF remains limited, and exposure timing complicates interpretation. Objective:To evaluate the association between early aspirin exposure and mortality in sepsis patients with AF. Methods:We conducted a retrospective cohort study using MIMIC-IV with external validation in eICU-CRD. Patients were classified according to aspirin exposure before ICU admission or within 48 h after ICU admission vs. no aspirin exposure within 48 h. A three-category sensitivity analysis further separated pre-ICU aspirin exposure from newly initiated aspirin within 48 h after ICU admission. In MIMIC-IV, the primary outcome was 30-day all-cause mortality and the secondary outcome was in-hospital mortality. Validation outcomes were in-hospital mortality and 30-day in-hospital mortality. Kaplan-Meier analysis, multivariable Cox regression, subgroup analyses, and weighted sensitivity analyses were performed. Results:In MIMIC-IV, 8,827 patients with sepsis and AF were included, of whom 2,175 had early aspirin exposure. Early aspirin exposure was associated with lower 30-day all-cause mortality; in the fully adjusted model, the hazard ratio was 0.624 (95% CI: 0.547-0.712; P < 0.001). In overlap-weighted analysis, this association remained significant (HR: 0.738, 95% CI: 0.647-0.842; P < 0.001). In the three-category sensitivity analysis, the inverse association was observed mainly among patients newly initiated on aspirin within 48 h after ICU admission. In eICU-CRD, early aspirin exposure was associated with lower in-hospital mortality in the fully adjusted model (HR: 0.732, 95% CI: 0.559-0.959; P = 0.024), whereas the association with 30-day in-hospital mortality was attenuated. Conclusion:Early aspirin exposure was associated with lower 30-day mortality in sepsis patients with AF, particularly among patients newly started on aspirin during early ICU care; associations with in-hospital mortality were less consistent.

Sepsis severity is associated with sustained neutrophilia, yet the underlying heterogeneity remains unclear. By integrating single-cell and bulk RNA-seq of septic peripheral blood, we uncovered five neutrophils clusters. FOLR3+neutrophils were the predominant and terminally differentiated subgroup, which displayed hyper-inflammatory signatures and low HLA expression, especially in non-survivors of sepsis. Cell-chat analysis also showed these neutrophils could promote sepsis progression by recruiting platelet via RETN-CAP1 and NAMPT-ITGB1 axes. External validation found that higher FOLR3+neutrophils were associated with 28-day mortality of sepsis. Transcription-factor and pseudotime analyses identified HIF-1A as the key driver of FOLR3+neutrophils specification. In vitro experiments validated that FOLR3 expression and HIF-1A were also found to be higher in sepsis. Over-expression or knockout of HIF-1A in patient and mouse neutrophils confirmed direct control of HIF-1A on secretion of IL-1β, TNF-α, IL-8 and IL-6. In conclusion, FOLR3+neutrophils contribute to sepsis prognosis by exacerbating hyper-inflammation and FOLR3 may serve as a new promising prognostic biomarker for sepsis.

Combined diquat and paraquat poisoning is a rare but clinically significant form of poisoning, associated with severe oxidative stress and multiorgan failure. Historical case series have reported high case fatality, particularly following high-dose exposure. The absence of specific antidotes and standardized treatment protocols for mixed poisoning necessitate innovative therapeutic approaches. We present the case of an adolescent girl in her early teens who ingested 100 mL of a commercially obtained but illegally formulated diquat–paraquat mixture (200 g/L). A novel low-metabolism strategy was implemented, comprising low-concentration oxygen therapy (fraction of inspired oxygen (21%–30%), targeted sedation/analgesia, β-blockade, temperature management, and multimodal detoxification). Plasma toxin levels decreased by >97% within 20 h. Despite complications including anuria, cerebral edema, and respiratory failure, the patient achieved complete recovery after 49 days. Low-metabolism strategy reduced cellular oxygen consumption, mitigated oxidative damage, and enabled effective elimination of toxins. Dynamic monitoring guided tailored organ support. The integration of low-metabolism strategy timely and multimodal detoxification may represent a promising, albeit resource-intensive, approach for severe bipyridinium herbicide poisoning. This strategy warrants further validation in controlled studies and offers a potential framework for cases with severe poisoning.

Acute lung injury significantly contributes to mortality in bacterial sepsis due to lung endothelial barrier destruction, leading to protein-rich lung edema, an influx of proinflammatory leukocytes, and persistent hypoxemia. CTRP3, an adipokine, reduces endothelial adhesion molecules Vcam-1 and Icam-1 and inhibits LPS-induced monocytic adhesion, highlighting its anti-inflammatory effects. This study investigates CTRP3's protective role in sepsis-induced acute lung injury, revealing reduced CTRP3 expression during sepsis, which worsens endothelial dysfunction. Supplementing with recombinant CTRP3 mitigates this dysfunction and reduces LPS-induced endothelial pyroptosis by inhibiting caspase-1, thus protecting the endothelial barrier and reducing lung injury. In conclusion, CTRP3 preserves endothelial function in sepsis by suppressing pyroptosis.

Sepsis represents a serious condition involving organ dysfunction that can be life-threatening, posing a significant threat to human health. The mortality rate associated with sepsis ranges from 10 http://bioinformatics.sdstate.edu/idep/ ) to identify differentially expressed genes. Conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses on the identified differentially expressed genes.To elucidate core genes from multiple perspectives, a PPI network was created with the help of the STRING database ( https://cn.string-db.org/),facilitatin g the examination of gene interactions in terms of protein. Following the recognition of core genes, sepsis-associated data sets were obtained from the Gene Expression Omnibus (GEO) public database. Specifically, the transcriptional expression of the gene S100A11 was analyzed using meta-analysis techniques, and its survival curve was subsequently evaluated.The S100A11 gene, identified through screening, was analyzed using an online visualization system to determine its single-cell localization. Initial findings indicated that the gene is predominantly expressed in macrophages. (THP-1 cells) are known as a human monocytic cell line utilized in studies.We cultured THP-1 cells and differentiated into macrophages, followed by stimulation and transfection with the S100A11 gene. The interference effect of S100A11 was assessed using quantitative fluorescence PCR (qPCR). Subsequently, THP-1 cells were cultured to establish a septic cell model, and S100A11 gene silence experiments were conducted, categorizing the samples into control, sepsis, and gene silence sepsis groups. ELISA was employed to assess the concentrations of the inflammatory cytokine IL-1β, TNF-α, and IL-6. Results demonstrated that S100A11 is highly expressed in sepsis and is primarily localized in macrophages. The enrichment in signaling pathways, including Th1 and Th2 cell differentiation, Th17 cell differentiation, Staphylococcus aureus infection, and cytokine-cytokine receptor interaction, was uncovered by differential gene expression analysis.S100A11 serves as a critical regulatory node for the inflammatory cytokines IL-1β, TNF-α, and IL-6. Notably, S100A11 was found to be highly expressed in patients with sepsis. This gene plays a crucial role in promoting inflammation during the septic inflammatory response and may be involved in macrophage differentiation, immunomodulation, and the inflammatory processes associated with sepsis.

ObjectiveThis study aimed to evaluate the effectiveness of a virtual reality (VR)-based training program in improving emergency physicians’ ability to manage multi-casualty traffic injuries, compared to conventional training methods.MethodsA randomized controlled trial was conducted with 76 emergency physicians from a single hospital. Participants were randomly assigned to either the VR group (n = 38) or the control group (n = 38). The VR group underwent immersive training using a VR simulation of multi-casualty traffic accidents, while the control group received traditional lectures and mannequin-based simulations. Primary outcomes included on-site assessment, triage accuracy, and decision-making in transportation, assessed immediately post-training. Secondary outcomes were participant satisfaction and confidence levels.ResultsThe VR group performed significantly better in on-site assessments (P < 0.05), triage accuracy (P < 0.05), and transportation decision-making (P < 0.05) compared to the control group. The VR group also reported higher satisfaction and confidence in applying learned skills in real-world situations (P < 0.05).ConclusionVR-based training enhances emergency physicians’ performance in managing multi-casualty traffic accidents, demonstrating its potential as a scalable and effective educational tool for emergency medical training.

PURPOSE:This study aimed to investigate the biometric characterization of pathogenic microorganisms associated with bloodstream infections in patients bitten by venomous snakes, and to determine whether the composition of these microorganisms influences the effects of snake venom. METHODS:The composition and relative abundance of microorganisms were statistically analyzed using metagenomic next-generation sequencing (mNGS) on blood samples from patients with varying degrees of snakebite injuries. These patients were admitted to the our study. RESULTS:In the light injury group (group L), the dominant phylum and genus were Pseudomonadota (73.31%) and Pseudomonas (35.32%). In the moderate injury group (group M), the predominant phylum was Bacillota (56.74%) and Aerococcus (45.45%). There was no statistically significant difference in the microbial composition between group L and group M based on α- and β-diversity analyses. LEfSe differential analysis revealed that the absolute abundances of Actinomycetota and Actinomycetes were higher in group L, while Pseudomonas aeruginosa emerged as a significantly differential species in Group M. CONCLUSION:The study found that differences in bacterial bloodstream infections due to venomous snakebite may enhance the effects of snake venom, leading to more severe injuries. The mNGS technique can rapidly detect pathogens related to venomous snakebites and has the potential for broader clinical use.

What is already known about this topic?:Human rabies remains nearly universally fatal despite medical advances. Diagnosis is frequently delayed when patients present with atypical symptoms, and the failure to receive postexposure prophylaxis (PEP) continues to be a major contributor to mortality worldwide. What is added by this report?:This represents the first confirmed human rabies case in Guangxi caused by the JSTZ190314 strain, successfully identified through metagenomic next-generation sequencing (mNGS). The patient initially presented with urinary symptoms that led to a misdiagnosis before characteristic neurological manifestations developed, ultimately progressing to brain death 28 days after neurological onset (34 days from initial urinary symptoms). What are the implications for public health practice?:This case demonstrates the critical importance of mNGS in diagnosing atypical rabies presentations and emphasizes the urgent need for enhanced early clinical recognition, standardized PEP administration protocols, and strengthened regional viral surveillance systems.

In China, it is estimated that over 100,000 snakebite incidents occur each year, significantly endangering human life. This study retrospectively analyzed the treatment data of Chinese cobra bite patients in a Chinese hospital from 2010 to July 2017. It was found that local necrosis typically occurs after a Chinese cobra bite, and effective treatment involves removal of the necrotic tissue and facilitating wound healing with anti-infection measures. The extent of local damage after the bite was correlated with creatine kinase levels. In addition, early administration of Chinese cobra antivenom was beneficial as it alleviated local necrosis and reduced the likelihood of adverse complications. However, under the current treatment protocols, the use or nonuse of Chinese cobra antivenom does not significantly impact survival outcomes.

OBJECTIVE:To investigate the antivenom mechanism of cytisine through network pharmacology and molecular docking (MD) techniques, with the intention of exploring its clinical applications.METHODS:The cytisine target and the snakebite respiratory inhibition target were obtained using the Swiss Target Prediction platform and the Gene Cards database. The two target sets were overlapped to form a protein interaction network. Additionally, pathway enrichment analysis was conducted on cross targets, and the related pathways for the treatment of snake venom-induced respiratory failure were obtained. Verification of the MD between cytisine and its related targets was performed using the Autodock 1.5.7 software. The respiratory depression model of rats bitten by venomous snakes was established, and the expression of key target genes in the rat model was verified by western blot (WB).RESULT:A total of 16 targets of cytisine and 9 potential targets of cytisine in treating snake venom-induced respiratory depression were obtained. Core targets including CHRNA7, CHRNG, CHRNB1, CHRND, CHRNA1 and DRD2 were obtained. These targets are mainly enriched in neuroactive ligand-receptor interaction pathway and cholinergic synaptic pathway. The MD results demonstrated favorable docking activity of cytisine with its related targets. WB experiments showed that snake venom reduced the levels of CHRNA7 and CHRNG. Treatment with serum and cytisine could slow down this decline.CONCLUSION:Cytisine may synergistically target CHRNA7, CHRNG, CHRNB1, CHRND, CHRNA1, DRD2 and other proteins, modulating cholinergic and neuroactive pathways to alleviate neuromuscular block and protect acetylcholine receptors.

In 2009, the World Health Organization included snakebite on the list of neglected tropical diseases, acknowledging it as a common occupational hazard for farmers, plantation workers, and others, causing tens of thousands of deaths and chronic physical disabilities every year. This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims. These recommendations are based on clinical experience and clinical research evidence. This guideline focuses on the following topics: snake venom, clinical manifestations, auxiliary examination, diagnosis, treatments, and prevention.

BackgroundContrast-induced nephropathy (CIN) can lead to serious complications following percutaneous coronary intervention (PCI). Urine N-Acetyl-β-D-glucosaminidase (uNAG) and serum homocysteine (sHCY) are both potential predictors for CIN detection, but their combination has not been explored. We aimed to combine uNAG and sHCY as predictors for the early detection of CIN and for prognosis prediction in patients after PCI.MethodsA total of 232 consecutive patients who underwent PCI at a university hospital were recruited for this study. According to the European Society of Urology and Reproduction (ESUR) criterion, CIN is defined as an elevation of serum creatinine (sCr) by ≥25% or ≥0.5 mg/dl from baseline within 48 h. We assessed the use of individual biomarkers (uNAG and sHCY) measured around PCI and their combinations for CIN detection and prognosis prediction. Receiver operating characteristic curves (ROC) and area under the curve (AUC) were used to evaluate the predictive efficiency of potential predictors.ResultsIn total, 54 (23.28%) patients developed CIN. Concentrations of uNAG and sHCY increased significantly in CIN subjects (p < 0.05) than non-CIN. CIN could be predicted by uNAG and sHCY but not by creatinine at an early stage. At pre-PCI, 0, 12, 24, and 48 h after PCI, the AUC-ROC value of uNAG in calculating total CIN was 0.594, 0.603, 0.685, 0.657, and 0.648, respectively. The AUC-ROC value of sHCY in calculating total CIN was 0.685, 0.726, 0.771, 0.755, and 0.821, respectively. The panel of uNAG plus sHCY detected CIN with significantly higher accuracy than either individual biomarker alone and earlier than sCr. For detecting total CIN, this panel yielded AUC-ROCs of 0.693, 0.754, 0.826, 0.796, and 0.844 at pre-PCI, 0, 12, 24, and 48 h after PCI, respectively, which were superior to those of the individual biomarkers. For predicting the incidence of major adverse cardiovascular events (MACE) within 30 days to 12 months, the AUC-ROC values for uNAG and sHCY measured before discharge were 0.637 and 0.826, respectively. The combined panel yielded an AUC-ROC of 0.832. The combined detection did not significantly enhance the predictive capability for MACE in patients with CIN. The CIN group and the non-CIN group showed no significant difference in the Coronary Heart Disease Intensive Care Unit (CCU) stay time, hospital stay time, demand for renal replacement therapy, CCU mortality rate, and in-hospital mortality rate.ConclusionsThe uNAG and sHCY panel demonstrated better sensitivity and specificity for predicting the diagnosis and prognosis of CIN in patients after PCI, earlier than sCr. The combination of these biomarkers revealed a significantly superior discriminative performance for CIN detection and prognosis compared to using uNAG or sHCY alone.

BACKGROUND:Immune infiltration plays a vital role in the course of acute myocardial infarction (AMI). Cuproptosis is a new type of programmed cell death discovered recently. Currently, there is no study on the mechanism of cuproptosis gene regulating immune infiltration in AMI. Therefore, by integrating cuproptosis-related genes and GEO database-related microarray data, this study analyzed the association between cuproptosis genes and immune infiltration and built a risk model. METHODS:The GSE59867 was used to extract cuproptosis gene expression profile. The R limma package was used to analyze the differentially expressed genes associated with AMI-Cuproptosis. The risk model was constructed according to AMI-cuproptosis differentially expressed genes. Prediction of AMI-cuproptosis-related gene drugs through Coremine Medical database. The upstream miRNAs were predicted using miRWalk, TargetScan, and miRDB libraries, and a miRNA-mRNA network was constructed. RESULTS:Cuproptosis-related genes (DLST, LIAS, DBT, ATP7A, LIPT1, PDHB, GCSH, DLD, DLAT) were down-regulated in AMI patients. One (ATP7B) gene was up-regulated in AMI patients (P<0.05). These 10 Cuproptosis-related genes were significantly associated with immune cell infiltration. Based on these 10 differential genes, the AMI risk prediction model was constructed, and the AUC value was 0.825, among which the abnormal expression of DLST was a risk factor for AMI. Additionally, we also predicted DLAT upstream miRNAs and associated drug targets, finding that 9 miRNAs were upstream of DLST. CONCLUSIONS:DLST is a potential cuproptosis gene associated with AMI, but its specific mechanism remains unclear and requires further investigation in future studies.

Background: Myocardial infarction is associated with the autophagy and apoptosis of cardiomyocytes, and the protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway plays a crucial role in this mechanism. Methods: Acute myocardial infarction rat models were assessed 0.5, 2, 4, and 6 hours after the induction of the myocardial infarction using hematoxylin and eosin staining, triphenyl tetrazolium chloride staining, myocardial enzyme measurements, and levels of autophagic activity. Additionally, diazoxide, 5-hydroxydecanoate, and LY294002 were intraperitoneally administered to rat models at peak myocardial injury to assess their effects on cardiac injury. The expression levels of autophagy-related and apoptosis-related proteins, as well as p-AKT and p-mTOR, were measured. Electron microscopy was used to assess the ultrastructure and the number of autophagosomes in the cardiac tissue. Results: We demonstrated that the degree of myocardial injury and the level of autophagy were significantly elevated in the experimental cohort compared with the control cohort. In addition, the myocardial infarct size was significantly smaller in diazoxide-treated acute myocardial infarction rats compared with untreated rats. Diazoxide also decreased the levels of myocardial injury markers, autophagy, and apoptosis, while it also induced the levels of AKT and mTOR phosphorylation, decreased the number of autophagosomes, and improved the myocardial ultrastructure of the acute myocardial infarction rats. 5-Hydroxydecanoate treatment resulted in an opposite effect to those observed upon diazoxide treatment. LY294002 was also able to reverse diazoxide treatment effects. Conclusion: Peak levels of myocardial tissue injury and autophagy were observed 2 hours post-acute myocardial infarction induction in rats. Diazoxide treatment inhibited myocardial autophagy and apoptosis while protecting cardiac tissue from ischemic injury, which is likely to have proceeded through activation of the AKT/mTOR pathway.

Background Inflammatory factors are well-established indicators for vascular disease, but the D-dimer to lymphocyte count ratio (DLR) is not measured in routine clinical care. Screening of DLR in individuals may identify individuals at in-hopital mortality of acute aortic dissection (AD). Methods A retrospective analysis of clinical data from 2013 to 2020 was conducted to identify which factors were related to in-hospital mortality risk of AD. Baseline clinical features, cardiovascular risk factors, and laboratory parameters were obtained from the hospital database. The end point was in-hospital mortality. Forward conditional logistic regression was performed to identify independent risk factors for AA in-hospital death. The cutoff value of the DLR should be ideally calculated by receiver operating characteristic (ROC) analysis. Results The in-hospital mortality rate was 15% (48 of 320 patients). Patients with in-hospital mortality had a higher admission mean DLR level than the alive group (1740 vs. 1010, P < .05). The cutoff point of DLR was 907. The in-hospital mortality rate in the high-level DLR group was significantly higher than that in the low-level DLR group ( P < .05). Univariate analysis showed that 8 of 38 factors were associated with in-hospital mortality ( P < .05), including admission WBC, neutrophils, lymphocytes, neutrophils/lymphocytes (NLR), prothrombin time (PT), heart rate (HR), D-dimer, and DLR. In multivariate analysis, DLR (odds ratio [OR] 2.127, 95% CI 1.034–4.373, P = 0.040), HR (odds ratio [OR] 1.016, 95% CI 1.002–1.030, P = 0.029) and PT (odds ratio [OR] 1.231, 95% CI 1.018–1.189, P = 0.032) were determined to be independent predictors of in-hospital mortality ( P < .05). Conclusion Compared with the common clinical parameters PT and HR, serum DLR level on admission is an uncommon but independent parameter that can be used to assess in-hospital mortality in patients with acute AD.