Editorial: Molecular mechanisms and clinical studies of multi-organ dysfunction in sepsis associated with pathogenic microbial infection

A Single-Cell Perspective Xu et al. employed single-cell RNA sequencing to investigate oxidative stress (OS) in sepsis, identifying LILRA5+ macrophages as key drivers of early OS surge. The study revealed that LILRA5 silencing reduced reactive oxygen species (ROS) levels in vitro, suggesting a potential therapeutic target. This work provides a high-resolution view of sepsis immunopathology and underscores the role of macrophage-mediated inflammation in disease progression.3. Neutrophil-to-Prognostic Nutritional Index (PNI) Ratio as a Novel Biomarker Lou et al. introduced the neutrophil/PNI ratio (NPR) as a prognostic marker for ICU mortality in sepsis. Their analysis of MIMIC-IV data showed a J-shaped association between NPR and mortality, particularly in elderly and obese patients. NPR integrates inflammatory and nutritional status, offering a simple yet effective risk assessment tool.4. Heparin-Binding Protein (HBP) and IL-6 in Severe Pneumonia with Sepsis Wei et al. compared HBP and IL-6 with conventional biomarkers in predicting 28-day mortality in sepsis secondary to severe pneumonia. IL-6 exhibited the highest discriminative power (AUC=0.80), surpassing CRP and lactate. Additionally, IL-6 was significantly elevated in bloodstream infections, supporting its role in early bacteremia detection.5. Creatinine-to-Albumin Ratio (CAR) in Sepsis-Associated AKI Another study by Lou et al. explored CAR as a predictor of 30-day mortality in sepsis-induced acute kidney injury (AKI). A threshold of CAR ≥ 1.2 mg/dL was associated with increased ICU mortality (HR=1.61), independent of metabolic and hemodynamic confounders. This ratio, easily calculated from routine lab tests, enhances risk stratification in critically ill patients.These studies collectively emphasize:1. Improved risk stratification: SOFA, APSIII, NPR, and CAR provide simple yet robust tools for mortality prediction. 2. Novel biomarkers: LILRA5, IL-6, and HBP offer mechanistic insights and potential therapeutic targets. 3. Heterogeneity in sepsis: Single-cell analyses reveal subtype-specific immune responses, paving the way for precision medicine. Future research should focus on: 1.Prospective validation of these models in diverse populations. 2. Integration of multi-omics data (e.g., metabolomics, proteomics) to refine predictive accuracy. 3. Interventional trials targeting identified biomarkers (e.g., anti-LILRA5 therapies).These findings significantly enhance sepsis management by improving early diagnosis, risk assessment, and personalized treatment strategies. The integration of computational models, biomarkers, and advanced sequencing techniques holds promise for reducing sepsis-related mortality worldwide.Keywords: Sepsis, Biomarkers, Predictive models, Oxidative stress, Acute kidney injury, Immune-metabolic interactions.