Inflammatory pathways and immune dysregulation in pediatric postoperative septic shock: A study integrating...

Area of Science:

• Pediatric critical care medicine
• Immunology
• Bioinformatics

Background:

• Pediatric postoperative septic shock is a life-threatening condition with complex molecular and immune underpinnings.
• Understanding these mechanisms is crucial for improving diagnosis and treatment strategies.

Purpose of the Study:

• To elucidate the molecular and immune regulatory mechanisms of pediatric postoperative septic shock.
• To identify key genes, pathways, and potential therapeutic targets, including traditional Chinese medicine interventions.

Main Methods:

• Transcriptomic data analysis using limma and Weighted Gene Co-expression Network Analysis.
• Functional enrichment analysis (GSEA, GO, KEGG) and immune cell infiltration assessment (ESTIMATE, CIBERSORT).
• Mendelian randomization, machine learning for feature gene selection, nomogram construction, and molecular docking.

Main Results:

• Identified 1331 differentially expressed genes, with the turquoise module strongly correlated to septic shock.
• Revealed activation of IL-6/JAK/STAT3, TNF-α/NF-κB, and PI3K/Akt/mTOR pathways and immune cell imbalances.
• Confirmed causal genes (e.g., PIM3), developed a high-performing diagnostic model, and identified quercetin and astramembrannin I as potential PIM3 binders.

Conclusions:

• Systematically identified core molecular and immune dysregulations in pediatric septic shock.
• Highlighted the potential of PIM3 as a diagnostic marker and therapeutic target.
• Suggested traditional Chinese medicine monomers as candidate interventions for targeted therapy.