ABSTRACT
[Objective]To investigate the effects of Kuanxiong aerosol(KXA)on pyroptosis and inflammatory response in isoproterenol(ISO)-induced myocardial infarction(MI)rats,and its effect on the key pathway of pyroptosis Toll-like receptor 4(TLR4)/myeloid differentiation primary response gene 88(MyD88)/NOD-like receptor pyrin domain containing 3(NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1).[Methods]Thirty male Wistar rats were randomly divided into five groups,6 rats in each group,as control group(0.9％sodium chloride solution),model group(ISO 120 mg·kg-1),isosorbide mononitrate(IMSN)group(ISO 120 mg·kg-1+IMSN 5 mg/kg·d),KXA low dose group(ISO 120 mg·kg-1+KXA 0.1 mL/kg·d),and KXA high dose group(ISO 120 mg·kg-1+KXA 0.3 mL/kg·d),gave continuous intragastric administration for 14 days,and intraperitoneal injection of ISO on the 13th and 14th day.After the last intervention,collected heart tissues and blood under anesthesia.Enzyme-linked immunosorbent assay(ELISA)was performed to investigate the expression of creatine kinase-MB(CK-MB)and cardiac troponin T(cTnT),as well as serum inflammatory indicators such as interleukin-1β(IL-1β),interleukin-18(IL-18),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α).The histopathological changes in heart tissue were evaluated using hematoxylin-eosin(HE)staining,and RNA-sequencing was used to detect the differential expression genes among groups.And the expression of the pyroptosis relevant protein was detected by Western blot.[Results]The results of the ELISA showed that CK-MB and cTnT expression in model group were significantly higher than those in control group(P＜0.01),which meant successful model construction.Pathological staining results showed disordered and fractured muscle fibers were significantly improved after KXA and IMSN intervention.RNA-seq results showed there were 2 646 different genes between model group and control group,while 714 other genes were in KXA and model group.After analyzing these two compared groups,it found that there were 130 up-regulated genes and 7 down-regulated genes;among them,inflammation related TLR4 pathway was significantly enriched.Furthermore,compared with model group,the expression of inflammatory factors IL-1β,IL-18,IL-6 and TNF-α decreased significantly in KXA groups and IMSN group(P＜0.01,P＜0.05),and Western blot showed that the protein expression of TLR4,MyD88,phospho-nuclear factor-KB(p-NF-KB)p65,NLRP3,cleaved cysteinyl aspartate specific proteinase-1(cleaved caspase-1)and Gasdermin D-N(GSDMD-N)increased significantly in model group while significantly down-regulated in KXA groups and IMSN group(P＜0.05,P＜0.01).[Conclusion]KXA can improve myocardial ischemia,reduce cardiac damage,and inhibit cardiomyocyte pyroptosis and inflammatory response,the mechanism may be related to regulating the TLR4/MyD88/NLRP3/caspase-1 signaling pathway.
ABSTRACT
Objective:To investigate the risk factors of pancreatic fistula after pancreaticoduodenectomy and establish the risk graph model of pancreatic fistula.Methods:The clinical data of 147 patients undergoing pancreaticoduodenectomy from Jan. 2018 to Jan. 2021 in Department of Hepatobiliary Surgery of Northern Theater Command General Hospital were retrospectively analyzed. The independent risk factors for postoperative pancreatic fistula were determined by univariate and multivariate analysis, and the linear graph model for predicting individual pancreatic fistula was drawn. The area under the subject operating characteristic curve was used to evaluate the model differentiation, the calibration curve was used to evaluate the model calibration, and finally the clinical application value of the model was evaluated by the clinical decision curve (DCA) .Results:The incidence of pancreatic fistula was 38.1%, including grade B pancreatic fistula in 49 cases and Grade C pancreatic fistula in 7 cases. Univariate analysis showed that operation method, body mass index (BMI), pancreatic texture, pancreatic duct diameter and lesion location were the related factors for postoperative pancreatic fistula. Multivariate analysis showed that BMI>25 kg/m 2, pancreatic soft texture, pancreatic duct diameter ≤3 mm and non-pancreatic diseases were independent risk factors for postoperative pancreatic fistula. According to the results of multiple factors, a prediction model of the nomogram was drawn, and the area under the subject operating characteristic curve of the model was calculated as AUC=0.792 (95% CI: 0.718-0.867). The calibration curve was drawn through internal verification of re-sampling, and the fitting curve swung around the 45° reference line, showing a high calibration degree; Clinical decision curve (DCA) analysis showed that the threshold probability was between 15% and 75% for maximum net benefit. It had good clinical application value. Conclusions:BMI>25 kg/m 2, soft pancreas, pancreatic duct diameter ≤3 mm and non-pancreatic diseases are independent risk factors for pancreatic fistula after pancreaticoduodenectomy. The established line graph model has good predictive efficiency and can effectively predict the occurrence of postoperative pancreatic fistula.