Revealing the role of gut microbiota in immune regulation and organ damage in sepsis using 16s rRNA and untargeted metabolomics / 中华危重病急救医学

OBJECTIVE@#To analyze the composition and metabolites of gut microbiota in septic rats by fecal 16s rRNA sequencing and untargeted metabolomics, and to preliminarily explore the effect and potential mechanism of gut microbiota and its metabolites on inflammatory response and multiple organ damage in sepsis.@*METHODS@#Ten males healthy male Wistar rats were randomly divided into a sham operated group (Sham group) and sepsis model group (CLP group) using a random number table method, with 5 rats in each group. A rat sepsis model was established by cecal ligation and perforation (CLP) method. The animals were sacrificed 24 hours after modeling, the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to observe the pathological changes of lung and kidney tissues, and the pathological scores were evaluated. Fecal samples were collected, and 16s rRNA high-throughput sequencing and non-targeted metabolomics were used to screen microbiota, metabolites and potential signal pathways that may play an important role in disease outcomes. Spearman correlation analysis was conducted to jointly analyze the gut microbiota and non-targeted metabolism.@*RESULTS@#Compared with the Sham group, the degree of pathological damage to lung and kidney tissues in the CLP group was significantly increased (lung tissue score: 3.60±0.80 vs. 0.00±0.00, kidney tissue score: 2.40±0.80 vs. 0.00±0.00, both P < 0.01), the level of IL-6 and TNF-α in peripheral blood significantly increased [TNF-α (ng/L): 248.12±55.98 vs. 143.28±36.57, IL-6 (ng/L): 260.26±39.47 vs. 116.01±26.43, both P < 0.05], the species diversity of intestinal flora of rats in the CLP group was significantly reduced, the relative abundance of Morganella, Bacteroides and Escherichia-Shigella were significantly increased, and the relative abundance of Lachnospiraceae NK4A136, Ruminococcus, Romboutsia and Roseburia were significantly reduced. In addition, the biosynthesis and bile secretion of phenylalanine, tyrosine, and tryptophan in the gut microbiota of the CLP group were significantly increased, while the biosynthesis of secondary bile acids was significantly reduced. There was a significant correlation between differential metabolites and differential microbiota.@*CONCLUSIONS@#Sepsis can cause significant changes in the characteristics of gut microbiota and fecal metabolites in rats, which provides a basis for translational research to seek new targets for the treatment of sepsis.

Role of different dose nicorandil in prevention of contrast-induced nephropathy in elderly CHD patients / 中华老年心脑血管病杂志

Objective To study the role of different dose nicorandil in prevention of CIN in elderly CHD patients.Methods One hundred and twenty-one elderly CHD patients were divided into standard dose nicorandil treatment group (n=42),5 mg nicorandil treatment group (n=39) and 10 mg nicorandil treatment group (n=40).Their Scr levels,and eGFR were measured for 3 days before and after PCI.The urine KIM-1 and NGAL levels were measured before and 24 h after PCI.The incidence of CIN and adverse reactions were compared in 3 groups.Results The incidence of (IN and the eGFR ≥25％ were significantly lower,the serum Scr level was significantly lower while the eGFR was significantly higher in 5 mg and 10 mg nicorandil treatment groups than in standard dose nicorandil treatment group on days 1 and 2 after PCI (P＜0.05,P＜0.01).The serum Scr level was significantly lower while the eGFR was significantly higher in 10 mg nicorandil treatment group than in 5 mg nicorandil treatment group on day 2 after PCI (P＜0.05).The urine KIM-1 and NGAL level were significantly lower in 10 mg nicorandil treatment group than in standard dose nicorandil treatment group and 5 mg nicorandil treatment group at 24 h after PCI (2.77±0.33 μg/L vs 5.63±0.27 μg/L,4.82±0.32 μg/L,P＜0.05;41.64±8.42 μg/L vs 66.51±10.72 μg/L,57.11±9.67 μg/L,P＜0.05).Conclusion Different oral doses of nicorandil play a role in prevention of CIN and 10 mg nicorandil plays a greater role than standard dose nicorandil and 5 mg nicorandil in prevention of CIN in elderly CHD patients undergoing PCI.