Coagulopathy in sepsis is common and is associated with high mortality. Although immunothrombosis is necessary for infection control, excessive thrombus formation can trigger a systemic thrombo-inflammatory response. Immunothrombosis plays a core role in sepsis-induced coagulopathy, and research has revealed a complex interplay between inflammation and coagulation. Different mechanisms underlying sepsis-related coagulopathy are discussed, including factors contributing to the imbalance of pro- and anticoagulation relevant to endothelial cells. The potential therapeutic implications of anticoagulants on these mechanisms are discussed. This review contributes to our understanding of the pathogenesis of coagulopathy in patients with sepsis. Recent studies suggest that endothelial cells play an important role in immunoregulation and hemostasis. Meanwhile, the non-anticoagulation effects of anticoagulants, especially heparin, which act in the pathogenesis of coagulopathy in septic patients, have been partially revealed. We believe that further insights into the pathogenesis of sepsis-induced coagulopathy will help physicians evaluate patient conditions effectively, leading to advanced early recognition and better decision-making in the treatment of sepsis.

This study aimed to explore the importance of routine coagulation tests for the early detection of sepsis and to quickly identify patients at a high risk of mortality. This retrospective single-center study collected data from patients meeting the clinical criteria for systemic inflammatory response syndrome (SIRS) with a confirmed infection source. Patients with coagulation disorders or on medications affecting coagulation were excluded. Patients were divided into sepsis and non-sepsis groups based on a Sequential Organ Failure Assessment (SOFA) score of ≥2. Univariate and multivariate logistic regression identified indicators from routine coagulation tests that predict sepsis. Prognostic roles of coagulation indicators were analyzed within the sepsis group. A total of 512 patients were included, with 396 in the sepsis group and 116 in the non-sepsis group. The predictive factors in the sepsis prediction model encompass fibrin degradation products (FDP), D-dimer, lactate, procalcitonin (PCT) levels and the utilization of mechanical ventilation. Early elevation of FDP and D-dimer levels predicted sepsis onset. The model exhibited an area under the curve (AUC) of 0.943 (95% CI: 0.923–0.963). In the sepsis group, Cox regression analysis revealed an association between prothrombin time (PT) and in-hospital mortality. Abnormal high FDP and D-dimer levels in the early stages of sepsis provide a supplementary method for predicting sepsis. As the disease progresses, prolonged PT in the early stages of sepsis suggests a poor prognosis.

Infectious complications (ICs) in acute pancreatitis (AP) are primarily driven by intestinal bacterial translocation, significantly increasing mortality and hospital stays. Despite this, the role of the gut microenvironment, particularly its metabolic aspects, in AP remains poorly understood. In this study, we investigated a cohort of patients with AP, and conducted supplemental murine studies, to explore the relationship between the gut metabolome and the development of ICs. Metabolomic analysis revealed that disruptions in gut tryptophan metabolism — especially reductions in serotonin and indole pathways — are key features associated with IC occurrence. Additionally, elevated plasma levels of tryptophan metabolites within the kynurenine pathway were identified as valuable predictive biomarkers for ICs. Mechanistic studies in murine models demonstrated that an impaired intestinal Th17 response, modulated by these tryptophan metabolites, plays a critical role in IC development. Serotonin supplementation enhanced Th17 responses, reducing IC incidence, while administration of kynurenic acid, a kynurenine metabolite, exacerbated pancreatic infections, potentially through immunosuppressive effects. These findings highlight the pivotal role of tryptophan metabolites in AP pathogenesis, emphasizing their potential as both predictive markers and therapeutic targets in IC management.

Heme oxygenase-1 (HO-1) protects cells by anti-oxidation, maintaining normal microcirculation and anti-inflammatory under stress. This study investigated the effects of biliary tract external drainage (BTED) on the expression levels of HO-1 in rat livers. Biliary tract external drainage was performed by inserting a cannula into the bile duct. Sixty Sprague–Dawley rats were randomized to the following groups: sham 1 h group; BTED 1 h group; bile duct ligation (BDL) 1 h group; sham 6 h group and BTED 6 h group. The expression levels of HO-1 mRNA were analyzed using real-time RT-PCR. The expression levels of HO-1 were analyzed using immunohistochemistry. The expression levels of HO-1 mRNA in the liver of the BTED group increased significantly compared with the sham group 1 and 6 h after surgery (p < 0.05).The expression levels of HO-1 in the BTED group increased significantly compared with the sham group 1 and 6 h after surgery. The expression levels of HO-1 mRNA in the liver in the BDL group decreased significantly compared with the sham group 1 h after surgery (p < 0.05).The expression levels of HO-1 in the BDL group decreased significantly compared with the sham group at this time. Biliary tract external drainages increase the expression levels of HO-1 in the liver.

Introduction: Sepsis caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) is associated with high mortality. Current research is predominantly pathogen-centric, creating a knowledge gap regarding the host’s systemic molecular response, which is critical for understanding outcomes and developing diagnostic strategies. This study aimed to characterize the host serum proteomic and metabolomic landscape of CRKP sepsis and to develop a proteomics-derived biomarker panel for differential diagnosis, while integrating metabolomic data to gain mechanistic insights into host pathways. Methods: Serum samples from sepsis patients, including culture-negative controls, and individuals infected with carbapenem-susceptible or carbapenem-resistant Klebsiella pneumoniae (CSKP and CRKP), underwent in-depth proteomic and metabolomic profiling. Differential expression, functional enrichment, and trend analyses were performed to characterize host molecular alterations associated with carbapenem resistance. Machine learning approaches were applied to construct diagnostic models based on host-derived molecular features. Candidate biomarker proteins were further validated using targeted parallel reaction monitoring (PRM) in an independent cohort. Results: We identified 85 differentially expressed proteins (DEPs) distinguishing CRKP from CSKP, enriched in viral infection-related pathways, antigen presentation, and phagosome function. Trend analysis revealed a protein cluster (51 proteins) with stepwise increased abundance from controls to CSKP to CRKP, implicating coagulation, immune signaling, and metabolic dysfunction. Based on proteomic data, a four-protein biomarker panel (IGHV1-8, ITGA2, PKP1, IGFBP6) effectively differentiated CRKP from CSKP (test AUC = 0.920). Targeted proteomic validation in an independent cohort confirmed the differential expression of key model proteins, including IGFBP6 (CRKP vs. CSKP) and APOA2 (CSKP vs. controls). Metabolomics identified 128 differential metabolites in CRKP vs. CSKP, with enrichment in thermogenesis and amino acid/fatty acid degradation pathways. Integrated pathway analysis of proteomic and metabolomic data highlighted dysregulation in cysteine/methionine metabolism and the folate-mediated one-carbon pool, with MAT2B as a key connecting protein. Conclusion: This first host-based multi-omics study of CRKP sepsis suggests distinct molecular signatures linked to resistance and disease severity. The independently validated biomarkers show high diagnostic potential, offering a preliminary foundation for early, non-invasive diagnosis and precision intervention strategies.