BackgroundSepsis is a life-threatening disorder characterized by multiple organ dysfunction caused by dysregulated host responses to infection. The present study aimed to identify potential diagnostic biomarkers for sepsis and elucidate their molecular mechanisms through comprehensive bioinformatics and experimental analyses.MethodsFive publicly available transcriptomic datasets (GSE13904, GSE26440, GSE28750, GSE95233, and GSE57065) containing sepsis and healthy control samples were utilized in the study. After quality control and normalization, the samples were divided into training and validation cohorts. Fourteen machine learning algorithms were applied to the training cohort to identify robust diagnostic biomarkers, and their predictive performance was subsequently verified in the validation cohorts. Single-cell RNA sequencing (scRNA-seq) data were further analyzed to determine the cellular distribution of the identified regulators among immune cell subsets.ResultsIn total, the least absolute shrinkage and selection operator (LASSO) model exhibited the best performance in the validation set, demonstrating high reliability. Through consensus feature selection across multiple models, the m6A methylation regulator fat mass and obesity-associated protein (FTO) was identified as a key biomarker. scRNA-seq analysis revealed that FTO was primarily expressed in neutrophils and macrophages. Its expression levels were markedly altered in peripheral blood mononuclear cells (PBMCs) and neutrophils from sepsis patients compared with healthy controls, which was consistent with the findings in in vitro macrophage and neutrophil models. Functional experiments demonstrated that FTO promotes macrophage polarization toward the pro-inflammatory M1 phenotype and enhances neutrophil inflammatory and chemotactic responses, highlighting its critical role in orchestrating inflammatory regulation during sepsis.ConclusionFTO, identified through consensus machine learning approaches, could serve as a potential diagnostic biomarker and m6A methylation regulator for sepsis. The discovery of FTO and its downstream targets provides new insights into sepsis pathogenesis and may offer a foundation for developing novel therapeutic strategies.

IntroductionProcalcitonin (PCT) is widely applied to guide antibiotic therapy, and its use—particularly for guiding antibiotic discontinuation—has been recommended in Chinese expert consensus for the past 5 years, in alignment with international guidelines. However, real-world adherence and optimal timing remain unclear.MethodsThis retrospective study analyzed adult patients with confirmed infections admitted to emergency intensive care units (EICUs) in 2023. Compliance with guidelines was assessed, focusing on stopping antibiotics when PCT dropped below 0.5 ng/mL or decreased by ≥80% within 24, 48, and 72 h after meeting criteria.ResultsAmong 195 patients, 52.3% met PCT criteria had a lower mortality rate than non-compliant cases (13.7% vs. 28.0%, p = 0.023). Early discontinuation within 24 h occurred in18.6% and was associated with shorter EICU stays (7 vs. 18 days), shorter antibiotic durations (6 vs.14 days), and lower antibiotic density (5.0 vs. 22.0 DDDs) without increasing mortality. Similar trends were observed when 48 and 72 h were used as cutoffs.DiscussionThe adherence to PCT-guided algorithms in routine practice in China—particularly timely discontinuation within 24 h—was low. Earlier discontinuation within 72 h was associated with shorter EICU stays and reduced antibiotic exposure. Importantly, no increase in mortality was observed. Further prospective studies are needed to confirm these findings.

Diffuse alveolar hemorrhage (DAH) is a life-threatening clinical condition characterized by bleeding into alveolar spaces,resulting in diffuse pulmonary infiltrates,hemoptysis,and hypoxemic respiratory failure.

Sedation during mechanical ventilation is common in intensive care units (ICUs). Functional near-infrared spectroscopy (fNIRS) has shown potential in monitoring brain function. This study aimed to evaluate and compare the brain functional connectivity (FC) characteristics in different sedated patients using fNIRS. Thirty sedated patients in the ICU and 16 conscious, non-sedated patients from the emergency ward were enrolled. Sedated patients were assigned to insufficient sedation (+ 1 to + 4), light sedation (-2 to 0), or deep sedation (-5 to -3) groups based on the Richmond Agitation Sedation Scale. Six-minute resting-state light intensity signals were collected using fNIRS and converted into a time series of relative oxyhemoglobin concentrations. FC characteristics of the overall brain and six regions of interest (ROIs) were compared using Pearson's correlation coefficients calculation. Multiple comparisons were corrected using the False Discovery Rate method. The deep sedation group had the highest overall mean FC compared with the other groups, which may be associated with the alterations of sedatives on cortical activity. ROI-level analyses revealed higher FC in the prefrontal, parietal, and occipital cortices in the deep sedation group than in the other groups. The deep sedation group had higher channel-channel and ROI-ROI FC in the FC matrices than the other groups. ROI-ROI connections differences were observed between the deep sedation and insufficient sedation groups. No significant difference in FC was identified between the light sedation group and the conscious control group. Deep sedation exhibited the highest overall and regional FC, and light sedation and the conscious state had similar FC patterns, supporting the potential utility of fNIRS for sedation monitoring in the ICU setting.Trial registration: ChiCTR2300068437 registration May 15, 2023, https://clinicaltrials.gov/ct2/show/ChiCTR2300068437.

Sepsis-induced cardiomyopathy (SICM) is a frequent yet potentially reversible form of acute myocardial dysfunction associated with high morbidity and mortality in septic shock. Increasing evidence suggests that alterations in the gut microbiota contribute to systemic inflammation and metabolic dysregulation during sepsis, highlighting the emerging importance of the gut–heart axis. However, the specific mechanisms through which microbiome-derived signals influence acute cardiac dysfunction remain incompletely understood. In this review, current evidence on gut microbial dysbiosis, metabolite-mediated signaling, and myocardial pathophysiology was synthesized to propose an integrative conceptual framework in which SICM represents a form of acute cardio-metabolic failure driven by time-dependent gut-derived inflammatory and metabolic perturbations. Key microbial metabolites, including short-chain fatty acids, bile acids, indole derivatives, trimethylamine-N-oxide, and phenylacetylglutamine, exert context-dependent effects on immune activation, mitochondrial energetics, calcium handling, and microcirculatory function. Notably, emerging data highlight important mechanistic paradoxes, such as divergent roles of specific metabolites in chronic cardiovascular disease versus acute sepsis, underscoring the need for disease/stage-specific interpretation of microbiome signaling. Translational challenges and opportunities for microbiome-targeted interventions in SICM were further discussed, including patient phenotyping, therapeutic timing, and integration with cardiac-focused supportive strategies in the intensive care setting. By positioning SICM within the broader paradigm of the gut–heart axis, this review provides a mechanistically grounded and clinically oriented perspective aimed at informing precision therapeutic approaches and future trial design in septic myocardial dysfunction.

BACKGROUND:Acute Respiratory Distress Syndrome (ARDS) is characterized by alveolar epithelial injury, inflammatory dysregulation, oxidative stress, and impaired repair capacity. Ferroptosis, an iron-dependent and lipid peroxidation-driven form of regulated cell death, has emerged as a pathogenic driver of ARDS; however, the upstream molecular regulators that initiate ferroptotic signaling in alveolar epithelial cells remain poorly defined. SERPINE1 (PAI-1), a mediator of inflammation, coagulation dysfunction, and epithelial injury, is frequently elevated in sepsis and ARDS, yet its mechanistic role in ferroptosis remains unknown. METHODS:Transcriptomic analysis of ARDS datasets, LPS-induced mouse models, clinical serum samples, and LPS-stimulated AT2 cells were used to assess SERPINE1 expression. Gain- and loss-of-function approaches, ferroptosis assays, mitochondrial functional analyses, NAD+/NADH quantification and proteomics were performed to define the regulatory relationship between SERPINE1, Sirt3, and ferroptosis. TM5275 was used to evaluate therapeutic modulation of SERPINE1 in vivo and in vitro. RESULTS:SERPINE1 was markedly upregulated in ARDS patients, ARDS mouse lungs, and LPS-treated AT2 cells, correlating with disease severity. SERPINE1 deficiency or pharmacologic inhibition significantly reduced lung injury, suppressed ferroptosis markers (ACSL4, ALOX12), and restored ferroptosis-inhibitory proteins (SLC7A11, GPX4, FTH1). Mechanistically, SERPINE1 did not directly bind Sirt3, but instead interacted with complex I subunits NDUFB10 and the NAD+-consuming enzyme PARP1, disrupting mitochondrial NAD+ homeostasis, decreasing the NAD+/NADH ratio, destabilizing mitochondrial membrane potential, and suppressing Sirt3 expression. These changes amplified ferroptotic signaling under inflammatory stress. CONCLUSION:Our findings identify SERPINE1 as a previously unrecognized upstream regulator that integrates inflammatory signaling, mitochondrial redox imbalance, and ferroptosis to drive epithelial injury in ARDS. The newly defined SERPINE1-NAD/NADH-Sirt3 axis reveals a metabolically driven mechanism of ferroptosis and suggests that targeting SERPINE1 may represent a promising therapeutic strategy to mitigate ferroptosis and ameliorate lung injury.

BACKGROUND:The dynamic crosstalk between N6-methyladenosine (m6A) RNA methylation and ferroptosis is pivotal for understanding disease pathogenesis. As the most abundant form of eukaryotic mRNA modification, m6A methylation guides RNA metabolism through writers, erasers, and readers. Ferroptosis, an iron-dependent and lipid peroxidation-driven form of cell death, occurs under conditions including dysregulated iron metabolism, compromised antioxidant defences, and lipid peroxidation. AIM OF REVIEW:This review highlights recent progress in basic research and proposes potential therapeutic targets for diseases of different systems while also addressing current drugs and challenges. KEY SCIENTIFIC CONCEPTS OF REVIEW: m6A RNA modification is governed by three types of effector proteins-writers, erasers, and readers-while the molecular mechanisms governing ferroptosis involve three interconnected biological axes: iron metabolism homeostasis, redox balance, and lipid peroxidation dynamics. Studies have indicated that m6A methylation regulates the expression of ferroptosis-related proteins, thus influencing tumorigenesis, progression and pathogenesis. This review also summarizes currently available agents targeting m6A-related targets as well as those associated with both m6A and ferroptosis, aiming to highlight their potential for clinical applications.

This narrative review synthesizes current evidence on the role of SERPINE1/PAI-1 in acute respiratory distress syndrome (ARDS), with particular emphasis on inflammation–coagulation–fibrinolysis crosstalk. Published experimental, translational, genetic, and clinical studies addressing SERPINE1/PAI-1 in ARDS and related critical illnesses were summarized. Not applicable. We summarized evidence on the pathobiological functions, cellular sources, biomarker potential, genetic associations, and therapeutic implications of SERPINE1/PAI-1. SERPINE1 limits tissue-type and urokinase-type plasminogen activator activity, thereby promoting hypofibrinolysis and persistent fibrin deposition in the injured lung. Experimental and clinical evidence further links elevated PAI-1 to inflammatory amplification, endothelial injury, pulmonary microvascular thrombosis, greater disease severity, and adverse outcomes, although the strength of evidence and the degree of causal support vary across these processes. High-expression SERPINE1 variants may also influence clinical outcomes in selected critical illness settings. Pharmacological PAI-1 inhibition is biologically plausible, but its translation to ARDS remains limited by disease heterogeneity, uncertainty regarding treatment timing, and the risk of bleeding. SERPINE1 is a potentially important integrative regulator and biomarker of dysregulated inflammation, coagulation, and fibrinolysis in ARDS. Future studies should clarify its causal, cell-specific, and phenotype-dependent roles to facilitate the development of targeted therapeutic strategies.

Septic cardiomyopathy (SCM) is a severe complication of sepsis with limited targeted treatment options, largely due to mitochondrial dysfunction in cardiomyocytes. Exophers, extracellular vesicles responsible for removing damaged mitochondria, represent a newly recognized mechanism of mitochondrial quality control, yet their upstream regulation remains unclear. This study tested the hypothesis that targeted degradation of Class I histone deacetylases (HDACs) using a PROTAC compound, JPS016, could alleviate SCM by promoting mitophagy-dependent exopher formation. An in vitro SCM model was established in HL-1 cardiomyocytes treated with lipopolysaccharide (LPS), and the effects of JPS016 on mitochondrial homeostasis, HDAC degradation, histone modifications, mitophagy, and exopher production were assessed using molecular and imaging techniques. JPS016 treatment significantly enhanced cell viability, reduced mitochondrial damage, and increased both histone acetylation and lactylation. Mechanistically, JPS016 activated the PINK1/Parkin mitophagy pathway and markedly increased the formation of exophers. Pharmacological inhibition experiments demonstrated that mitophagy, rather than general autophagy, was essential for exopher biogenesis and the protective effect of JPS016. These findings identify HDAC degradation as a novel upstream regulator of exopher-mediated mitochondrial clearance and support the therapeutic potential of PROTAC-based interventions in SCM.

BACKGROUND:Inappropriate antibiotic treatment for patients with viral infections has led to a surge in antimicrobial resistance, increasing mortality and healthcare costs. Viral and bacterial infections are often difficult to distinguish. Myxovirus resistance protein A (MxA), an essential antiviral factor induced by interferon after viral infection, holds promise for distinguishing between viral and bacterial infections. This study aimed to determine the ability of MxA to distinguish viral from bacterial infections. METHODS:We quantified MxA in 121 infected patients via dry immunofluorescence chromatography. The Kruskal-Wallis test and receiver operating characteristic (ROC) curve analysis were used to determine the diagnostic value of MxA, either alone or in combination with C-reactive protein (CRP) or procalcitonin (PCT), in patients with viral, bacterial, or co-infections. RESULTS:The value of MxA (ng/mL) was significantly higher in patients with viral infections than in those with bacterial and co-infections (82.3 [24.5-182.9] vs. 16.4 [10.8-26.5], P<0.0001) (82.3 [24.5-182.9] vs. 28.5 [10.2-106.8], P=0.0237). The area under the curve (AUC) of the ROC curve for distinguishing between viral and bacterial infections was 0.799 (95% confidence interval [95% CI] 0.696-0.903), with a sensitivity of 68.9% (95% CI 54.3%-80.5%) and specificity of 90.0% (95% CI 74.4%-96.5%) at the threshold of 50.3 ng/mL. Combining the MxA level with the CRP or PCT level improved its ability. MxA expression was low in cytomegalovirus (15.8 [9.6-47.6] ng/mL) and Epstein-Barr virus (12.9 [8.5-21.0] ng/mL) infections. CONCLUSION:Our study showed the diagnostic efficacy of MxA in distinguishing between viral and bacterial infections, with further enhancement when it was combined with CRP or PCT. Moreover, Epstein-Barr virus and human cytomegalovirus infections did not elicit elevated MxA expression.

BACKGROUND:Sepsis-associated encephalopathy (SAE) is a diffuse dysfunction of the nervous system resulting from sepsis originating outside the central nervous system. Elderly individuals (≥65 years of age) constitute a particularly vulnerable population comprised by a high burden of underlying diseases and complications, which frequently leads to underdiagnosis or misdiagnosis. These patients are at increased risk of long-term or permanent central nervous system impairment, making rapid and accurate diagnosis and treatment especially critical. The review is expected to promote improvements in the diagnosis and treatment of SAE in elderly patients, ultimately achieving more standardized and efficient SAE management. METHODS:We performed a literature search in four databases-PubMed, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang-from inception to April 2025 using bilinguals (Chinese and English). RESULTS:The diagnostic criteria for SAE in elderly individuals include the following: (1) sepsis; (2) new-onset neurological dysfunction; and (3) exclusion of other causes of neurological dysfunction. Physicians should develop tailored empiric anti-infective plans for elderly SAE patients, considering comorbidities, organ function, infection site, local bacterial spectrum, and resistance. The treatment protocol can be adjusted once the pathogen is identified. Stabilizing hemodynamics and ensuring cerebral perfusion are two fluid resuscitation strategies used in elderly SAE patients. An individualized approach to fluid resuscitation using restrictive fluid volumes should be employed. Supportive treatment for elderly SAE patients focuses on improving tissue perfusion/oxygenation, controlling blood glucose levels, and correcting internal imbalances. Early rehabilitation, nutritional support, cognitive training, and family-based emotional support are important components of comprehensive care. CONCLUSION:The diagnosis and management of SAE in elderly patients support early recognition and timely intervention.

BACKGROUND:Post-resuscitation myocardial dysfunction is one of the major causes of death in post-cardiac arrest patients. Pyridostigmine (PYR) shows protective effects on myocardial ischemia-reperfusion injury following myocardial infarction and left heart failure by improving autonomic nervous function. This study aimed to investigate the effects of low-dose pyridostigmine on post-resuscitation myocardial dysfunction. METHODS AND RESULTS:A rat model of cardiac arrest and resuscitation was induced by ventricular fibrillation (VF). The rats were randomly categorised into the following four groups: control (Con), Control + PYR (Con-PYR), Cardiac arrest (CA), and Cardiac arrest + PYR (CA-PYR) groups. PYR was administered to rats at 0.25 mg/kg before VF induction by intraperitoneal injection. At 24 h after return of spontaneous circulation (ROSC), echocardiography, heart rate variability, and invasive haemodynamics were measured. Blood and heart tissue samples were collected for further analysis. PYR improved the hypoxic state in the rat model of cardiac arrest and resuscitation. It significantly improved left ventricular systolic function and hemodynamics compared with the CA group. Additionally, it reduced myocardial injury, improved mitochondrial dysfunction, and decreased myocardial inflammation and apoptosis in the rat model of cardiac arrest and resuscitation. It reduced the left ventricular protein expression of muscarinic acetylcholine type 2-receptor, increased power spectral analysis of heart rate variability, and partially restored autonomic nervous function in this rat model. CONCLUSIONS:Low-dose PYR improved autonomic nervous function, reduced myocardial injury and inflammation, and improved cardiac dysfunction in rat model of cardiac arrest and resuscitation.

KW-2449 is a novel multitargeted kinase inhibitor that has been reported to alleviate chronic inflammation and altered immunity during the treatment of autoimmune diseases. The aim of the study was to investigate the effect of KW-2449 on sepsis-induced cardiomyopathy (SIC). A rat model of moderate SIC was induced using the cecal ligation and puncture (CLP) method. KW-2449 was administered to rats at 10 mg/kg for 3 consecutive days by intraperitoneal injection. At 24 hours after CLP, echocardiography, electrocardiogram, and hemodynamic analyses were performed. Blood and cardiac tissues were collected for further analysis. RNA sequencing (RNA-seq) analyses were used to identify the key genes affected by KW-2449 treatment during SIC. KW-2449 improved the liver dysfunction in septic rats. KW-2449 significantly improved left ventricular (LV) systolic function and hemodynamics compared to the CLP group. KW-2449 suppressed the systemic inflammatory response, decreased myocardial inflammation and cell apoptosis in the CLP rats. RNA-seq analyses indicated that there were a total of 2256 differentially expressed genes in the CLP group compared to the Control group, among which 63 genes were down-regulated and 59 genes were up-regulated by KW-2449. Specifically, Pparα was identified as a key target gene of KW-2449 in the treatment of SIC by RNA-seq analysis.KW-2449 also significantly upregulated the protein expression of Pparα in the LV tissue of septic rats. KW-2449 reduced systemic inflammation, cardiac inflammation, and improved cardiac dysfunction in the CLP-induced SIC rat model. The underlying mechanism of the cardio-protective role of KW-2449 in the CLP-induced SIC might be related to Pparα.

Sepsis-associated encephalopathy (SAE) is a diffuse dysfunction of the nervous system resulting from sepsis originating outside the central nervous system. The elderly (≥65 years of age) are a particularly vulnerable population, and the emergency department is typically the first point of contact following onset of SAE. Clinical symptoms in elderly patients with SAE are often atypical, compounded by a high burden of underlying diseases and complications, which frequently leads to underdiagnosis or misdiagnosis. These patients are at increased risk of long-term or permanent central nervous system impairment, making rapid and accurate diagnosis and treatment especially critical. Currently, there are no standardized diagnostic or treatment guidelines tailored specifically to geriatric SAE. This expert consensus, grounded in evidence-based medicine and clinical experience, offers recommendations on the risk factors, clinical characteristics, diagnosis, and treatment of geriatric SAE. The goal is to standardize care, improve diagnostic accuracy, reduce mortality, and enhance patient outcomes.

Community-acquired pneumonia(CAP)in adults(≥18 years old)is the most common infectious disease encountered in emergency de-partments.Its clinical complexity and the need for prompt treatment decisions pose significant challenges for patient management.The physician-pharmacist collaborative management(PPCM)model,which optimizes drug therapy regimens through collaboration between physicians and clinical pharmacists,has demonstrated strong clinical value in practice.However,the lack of standardized national guide-lines for the application of the PPCM model in emergency departments in China has hampered its widespread adoption.This guideline is developed based on evidence-based medicine and clinical practice experience,with a focus on the application of the PPCM model in the management of CAP in emergency settings.It outlines the significance of the PPCM model,its applicable scenarios,the respective roles of emergency physicians and clinical pharmacists,and its practical implementation in the antimicrobial treatment of CAP patients.In addition,the guideline proposes standardized implementation processes and clinical pathways.By promoting the PPCM model,the expert panel aims to standardize the use of antimicrobial agents in the emergency treatment of CAP,reduce the risk of antimicrobial resistance,and improve patient outcomes.

BACKGROUND:Post-cardiac arrest syndrome (PCAS) significantly contributes to mortality after initially successful cardiopulmonary resuscitation (CPR) in cardiac arrest (CA) patients. Effective cardiocerebral protection is essential for improving post-resuscitation survival. This study investigated the mechanisms and common targets of myocardial dysfunction and brain injury after resuscitation. METHODS:The male Sprague-Dawley rats (10-12 weeks old, 400-500 g) were divided into two groups: the control group (n=6), which received sham surgery, and the CA/CPR group (n=10), which received ventricular fibrillation (VF) followed by CPR. After 24 h, brain and heart tissues were collected for analysis. The sequencing was used to identify differentially expressed genes (DEGs) between control and CA/CPR rats. RESULTS:At 24 h after resuscitation, CA/CPR rats presented 217 DEGs in the hippocampus and 80 DEGs in the left ventricle (LV) compared to the control group. In the hippocampus, the most notable biological process was the positive regulation of tumor necrosis factor production, with key pathways related to inflammation and the immune response. In the LV, the Gene Ontology (GO) enrichment analysis revealed that gene alterations were primarily associated with amyloid-beta clearance, a pathway that was also relevant in the brain. Eleven common targets were identified in the DEGs of both heart and brain tissues. The reverse transcription-polymerase chain reaction (RT-PCR) validation revealed significant differences in the mRNA expression of Timp1, Apln, Ccl7, and Lgals3 in both LV and hippocampus. CONCLUSION:This study identified possible key genes and underlying mechanisms involved in PCAS. The differential genes Timp1, Apln, Ccl7, and Lgals3 might serve as common biomarkers for myocardial and neurological injury following resuscitation.

OBJECTIVE AND DESIGN:This study aims to identify key genes of sepsis and construct a model for sepsis identification through integrated multi-organ single-cell RNA sequencing (scRNA-seq) and machine learning. MATERIAL OR SUBJECTS:Datasets downloaded from the Gene Expression Omnibus (GSE207363, GSE207651, GSE185263, GSE69063 and GSE134347) were used. METHODS:ScRNA-seq data extracted from heart (GSE207363) and lung tissues (GSE207651) of septic mice were processed and analyzed using the Seurat package in R. Key genes were identified as present in both heart and lung tissues, resulting from the overlap of three analyses along with differential expression analyses. We then used support vector machine recursive feature elimination to construct a model for sepsis identification based on these key genes. The GSE185263 dataset was used for training, while GSE69063 and GSE134347 were used for testing. The accuracy of the model in identifying of sepsis was validated by analyzing the area under the receiver operating characteristic curve (AUROC) using the test datasets. RESULTS:Thirteen genes were initially identified as key genes, and after translation to their human homologs, ten genes remained. The optimal SVM-RFE model incorporated eight of these genes (CAMP, CD74, HLA-DQA1, HLA-DQB1, HLA-DMA, HLA-DRB5, and LYZ). In the two test datasets, the AUROC value for the accuracy of the model in identifying of sepsis was 0.904 and 0.924, respectively. CONCLUSIONS:We have identified several key genes and developed a machine learning model for sepsis identification. Further studies are needed to validate our findings.

BACKGROUND: This study aims to explore whether Xuebijing (XBJ) can improve intestinal microcirculation dysfunction in sepsis and its mechanism. METHODS: A rat model of sepsis was established by cecal ligation and puncture (CLP). A total of 30 male SD rats were divided into four groups: sham group, CLP group, XBJ + axitinib group, and XBJ group. XBJ was intraperitoneally injected 2 h before CLP. Hemodynamic data (blood pressure and heart rate) were recorded. The intestinal microcirculation data of the rats were analyzed via microcirculation imaging. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect the serum levels of interleukin-6 (IL -6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-alpha) in the rats. Histological analysis and transmission electron microscopy were used to analyze the injury of small intestinal microvascular endothelial cells and small intestinal mucosa in rats. The expression of vascular endothelial growth factor A (VEGF-A), phosphoinositide 3 -kinase (PI3K), phosphorylated PI3K (p-PI3K), protein kinase B (Akt), and phosphorylated Akt (p -Akt) in the small intestine was analyzed via Western blotting. RESULTS: XBJ improved intestinal microcirculation dysfunction in septic rats, alleviated the injury of small intestinal microvascular endothelial cells and small intestinal mucosa, and reduced the systemic inflammatory response. Moreover, XBJ upregulated the expression of VEGF-A, p-PI3K/total PI3K, and p-Akt/total Akt in the rat small intestine. CONCLUSION: XBJ may improve intestinal microcirculation dysfunction in septic rats possibly through the VEGF-A/PI3K/Akt signaling pathway.

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.