Background: Sepsis is a systemic inflammatory disease, and Brevilin A (BA) has a powerful anti-inflammatory effect. However, whether BA has a similar effect on septic cardiomyopathy remains unclear. This study aimed to investigate the effect and mechanism of BA in septic cardiomyopathy. Methods: First, a model of septic cardiomyopathy was constructed in vitro and vivo. The expression of the cardiac injury markers, NOD–like receptor family pyrin domain–containing 3(NLRP3) inflammation factors and its upstream modulator NF-κB was detected by Real-time Polymerase Chain Reaction (RT-PCR) and western blotting. Cardiac function was measured using Echocardiography, Cell viability was detected using the methyl thiazolyl tetrazolium assay (MTT). To further investigate the effects of BA on septic cardiomyopathy, different concentrations of BA were used, the experiment was divided into Control group, LPS induced- group, LPS+2.5, 5.0, 10.0 μM BA treatment group of the vitro model, and Sham, CLP, CLP+10, 20, 30 mg/kg BA treatment group of the rat vivo model. Lastly, cardiac injury, NLRP3 inflammation, and cardiac function were assessed in each group. Results: The mRNA and protein expression of cardiac inflammation and injury genes were significantly increased in the in vitro and in vivo sepsis cardiomyopathy models. When different concentrations of BA were used in sepsis cardiomyopathy in vivo and in vitro, the above-mentioned myocardial inflammation and injury factors were suppressed to varying degrees, cell viability increased, cardiac function improved, and the survival rate of rats also increased. Conclusion: BA ameliorated sepsis cardiomyopathy by inhibiting NF-κB/ NLRP3 inflammation activation. Export

Background: This study aimed to identify a key target gene in proximal tubule cells (PTCs) of sepsis-induced acute kidney injury (S-AKI) and elucidate the underlying mechanisms. Methods: We screened and analyzed GEO datasets and identified a key gene, GATM, in S-AKI. An S-AKI mouse model was established via intraperitoneal injection of lipopolysaccharide (LPS), and HK-2 cells were used for in vitro experiments. The role of GATM was evaluated using adeno-associated virus (AAV)-mediated overexpression in mice and plasmid-mediated overexpression in HK-2 cells. To identify the downstream target genes of GATM, transcriptome sequencing was conducted. Pathological evaluation was performed using hematoxylin–eosin (HE) and periodic acid–Schiff (PAS) staining. Protein levels were determined by Western blotting (WB), immunohistochemistry (IHC), and immunofluorescence (IF) assays; Apoptosis was evaluated by TUNEL staining; Mitochondrial morphology and function were assessed by transmission electron microscopy (TEM), JC-1 and MitoSOX assays. Lactate concentration and cellular ATP levels were measured. Results: Through analysis of four datasets (GSE151658, GSE247727, GSE220812, and GSE139061), GATM was identified as a key gene in PTCs during S-AKI. GATM expression was downregulated in both S-AKI mice and LPS-stimulated HK-2 cells. In vivo, GATM overexpression improved renal function, alleviated tubular damage, decreased the expression of KIM-1, IL-6, Caspase-3, and 4-HNE, and reduced mitochondrial injury. In vitro, HK-2 cell viability was enhanced, TUNEL-positive cells were reduced, and damaged mitochondria were decreased. Transcriptome sequencing revealed that the PDK4-mediated glycolysis pathway was a downstream target of GATM. GATM overexpression downregulated PDK4 expression, reduced glycolytic enzyme levels (p-PDHA, HK2, LDHA, GLUT1) and lactate, and increased ATP production. However, PDK4 overexpression in HK-2 cells abolished the protective effects of GATM, enhanced glycolysis, increased lactate levels, and reduced ATP production. Conclusion: GATM plays a protective role in S-AKI by inhibiting PDK4-mediated aerobic glycolysis, enhancing ATP production, and restoring energy metabolism and mitochondrial function in PTCs.

Electric shock injuries, a category of severe industrial accidents, often entail the risk of multi-organ damage. In the present unique case report, the infrequent occurrence of a right scapular fracture stemming from an electric shock accident is described. A male patient in his early 30s accidentally received an electric shock while working, resulting in pain in the right upper limb and shoulder. Although he had no obvious external injuries, physical examination revealed a decrease in muscle strength in the right upper limb. Following magnetic resonance imaging and computed tomography, a comminuted fracture of the scapula was diagnosed. The patient received emergency symptomatic treatment, including pain relief, anti-infection measures, and nutritional support for the myocardium, and subsequent orthopaedic surgical intervention for fracture fixation. The patient recovered well after surgery, with muscle strength gradually returning. This report documents the rarely-described occurrence of non-traumatic unilateral scapular fractures following an electric shock. Medical practitioners should be aware of the wide range of potential injuries, including fractures, when evaluating patients with electric shock injuries.

A comprehensive assessment of combined modifiable risk factors in relation to infectious diseases among individuals with hypertension is lacking, and the potential mechanisms of these associations remain unclear. To investigate the prospective associations of a combination of lifestyle behaviors and cardiometabolic factors with the risk of infectious diseases among individuals with hypertension and to estimate whether and to what extent blood biomarkers mediate these associations. This cohort study included 147,188 participants with hypertension and complete data on modifiable risk factors from the UK Biobank. Health score was constructed from eight modifiable risk factors, including four lifestyle behaviors (diet, physical activity, smoking, and sleep duration) and four cardiometabolic factors (body mass index, blood lipids, blood glucose, and blood pressure). Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the health score and infectious diseases. The mediation analysis was performed to assess the potential intermediation effects of blood biomarkers. Over a median follow-up of 12.5 years, 27,398 participants with infectious diseases were documented, with 960 respiratory infectious diseases and 7940 digestive infectious diseases. After adjusting for potential confounders, the HR (95% CI) for the highest versus the lowest quartile of health score was 0.64 (0.62, 0.66) for infectious diseases, 0.72 (0.60, 0.86) for respiratory infectious diseases, and 0.66 (0.62, 0.71) for digestive infectious diseases. Stratified factors including duration of hypertension did not modify the associations between the health score and infectious diseases. In addition, biomarkers including inflammation and renal function collectively explained 46.60% of the associations between the combined lifestyle factors and infectious disease risk among individuals with hypertension. Ideal management of combined modifiable risk factors was associated with lower risks of infectious diseases and might produce profound changes in blood biomarkers among individuals with hypertension. Additionally, specific biomarkers appeared to serve as an intermediate between combined lifestyle factors and infectious diseases. These insights highlighted the important role of a combination of healthy lifestyle and favorable cardiometabolic status in reducing disease burden and facilitated the understanding of biological mechanisms underlying modifiable risk factors with infectious diseases.