Integrated Single Cell and Bulk RNA-Seq Analysis Revealed Immunomodulatory Effects of Ulinastatin in Sepsis: A Multicenter Cohort Study.

Sepsis is a leading cause of morbidity and mortality in the intensive care unit, which is caused by unregulated inflammatory response leading to organ injuries. Ulinastatin (UTI), an immunomodulatory agent, is widely used in clinical practice and is associated with improved outcomes in sepsis. But its underlying mechanisms are largely unknown. Our study integrated bulk and single cell RNA-seq data to systematically explore the potential mechanisms of the effects of UTI in sepsis. After adjusting for potential confounders in the negative binomial regression model, there were more genes being downregulated than being upregulated in the UTI group. These down-regulated genes were enriched in the neutrophil involved immunity such as neutrophil activation and degranulation, indicating the immunomodulatory effects of UTI is mediated via regulation of neutrophil activity. By deconvoluting the bulk RNA-seq samples to obtain fractions of cell types, the Myeloid-derived suppressor cells (MDSC) were significantly expanded in the UTI treated samples. Further cell-cell communication analysis revealed some signaling pathways such as ANEEXIN, GRN and RESISTIN that might be involved in the immunomodulatory effects of UTI. The study provides a comprehensive reference map of transcriptional states of sepsis treated with UTI, as well as a general framework for studying UTI-related mechanisms.

Therapeutic effect of low-molecular-weight heparin on adult sepsis: a meta-analysis.

BACKGROUND: Low-molecular-weight heparin (LMWH) is a part of standard supportive therapy for sepsis, but clinical research on anticoagulant therapy is still controversial. The aim of the present study was to explore the efficacy and safety of LMWH in adult septic patients by meta-analysis. METHODS: Information on randomized controlled trials was retrieved from PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and China Wanfang Database from the establishment of each database to February 20, 2020. The therapeutic efficacy indexes of LMWH for adult septic patients were analyzed by Stata15.0 software. RESULTS: A total of 684 septic patients were included in 10 trials. The results showed that, compared with conventional treatment, LMWH significantly reduced prothrombin time [mean difference (MD) =-0.48, 95% confidence interval (CI): -0.83 to -0.13], Acute Physiology And Chronic Health Evaluation II score (MD=-4.42, 95% CI: -5.50 to -3.33), and 28-day mortality [relative risk (RR) =0.52, 95% CI: 0.38-0.70], and increased platelet count (MD =34.99, 95% CI: 23.37-46.60). LMWH significantly reduced levels of tumor necrosis factor-α, interleukin-6, and D-dimer, and the incidence of multiple organ dysfunction syndrome (MODS), with statistically significant differences. In addition, LMWH did not increase bleeding events (RR =1.29, 95% CI: 0.76-2.17). CONCLUSIONS: On the basis of routine treatment, LMWH can improve coagulation function, reduce inflammatory reaction and the risk of bleeding, reduce the incidence of MODS and 28-day mortality rate, and improve the prognosis of adult patients with sepsis.