ABSTRACT
Objective:To explore the role of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in non-alcoholic steatohepatitis (NASH).Methods:The liver tissue samples of 24 patients admitted the Second Affiliated Hospital of Fujian Medical University were selected, including 12 NASH samples from liver biopsy and 12 normal liver tissues from the margin of hepatic hemangioma. The expression of NLRP3, apoptosis-associated speck-like protein (ASC), caspase-1, interleukin (IL)-1β and the content of triglyceride (TG) were detected. Wild-type and NLRP3 -/- C57BL/6 mice were fed with normal diet or methionine-choline deficient diet (MCD) for 8 weeks. The wild-type mice were divided into MCC950 NASH, 0.9% sodium chloride (NaCl) NASH, MCC950 and 0.9% NaCl group, 8 mice in each group, and were fed with MCD diet and treated with MCC950, fed with MCD diet and treated with 0.9% NaCl, fed with normal diet and treated with MCC950, and fed with normal diet and treated with 0.9% NaCl respectively for eight weeks. After eight weeks, the pathologic changes of liver tissues were observed with hematoxylin-eosin staining and immunohistochemistry. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), free fatty acid (FFA), IL-1β and TG in serum were determined by enzyme linked immunosorbent assay. The expression levels of NLRP3, ASC, caspase-1 and IL-1β in liver tissues were examined by Western blotting and real-time quantitative polymerase chain reaction. Primary Kupffer cells were isolated and cultured from the livers of wild-type and NLRP3 -/- mice and divided into control group and palmitic acid group. The expression levels of related proteins in the supernatant of cells culture were detected by Western blotting. Independent sample t test and one-way ANOVA were used for statistical analysis. Results:The expression levels of NLRP3, ASC, caspase-1, IL-1β and the content of TG of the liver tissues of the NASH patients were all higher than those of healthy control group (all P<0.05). The formation of steatohepatitis in hepatocyte of MCD-fed mice was more obvious than that of nomal diet-fed mice, with more hepatocyte ballooning and inflammatory cell infiltration. The expression of NLRP3, ASC, caspase-1, IL-1β, caspase-1 activity and the content of TG in liver tissue of NASH mice were all higher than those of normal diet-fed group (all P<0.05); and serum levels of ALT, AST, IL-1β, and the content of FAA were all higher than those of normal diet-fed group (all P<0.05). The serum levels of ALT, AST, IL-1β and IL-18 of NLRP3 -/- NASH mice were all lower than those of wild-type NASH mice (all P<0.05). The serum level of ALT, the expression of ASC, caspase-1 and IL-1β in liver tissues, and the degrees of liver fibrosis of wild-type MCC950 NASH group were all lower than those of 0.9% NaCl NASH group (all P<0.05). The expression of NLRP3, ASC, caspase-1, caspase-1 activity, and secretion of IL-1β and IL-18 in Kupffer cells from wild-type mouse treated with palmitic acid were all higher than those of the negative control group (all P<0.05). However, the changes of the above indicators in Kupffer cells from NLRP3 -/- mouse were not affected by palmitic acid treatment. Conclusion:NLRP3 blockade can significantly alleviate the liver injury and fibrosis in NASH mice and prevent the development of NASH.
ABSTRACT
Objective To investigate the effect of low-dose aspirin combined with rabeprazole on the healing of peptic ulcer after hemostasis with aspirin-related peptic ulcer bleeding,and to explore the independent factors associated with ulcer healing failure.Methods A total of 138 patients with acute upper gastrointestinal hemorrhage in the Department of Gastroenterology of the Second Affiliated Hospital of Fujian Medical University from June 2016 to June 2018 were enrolled.The clinical data of 138 patients with upper gastrointestinal ulcer bleeding caused by aspirin were analyzed.The patients were randomly divided into two groups.Aspirin group (n =68) received aspirin 100 mg/d plus rabeprazole 80 mg/d,while the placebo group (n =70) received rabeprazole 80 mg/d plus placebo.The patients were treated for 8 weeks.Subjects with H.pylori infection were treated with standard quadruple therapy.Follow-up endoscopy was performed at the end of 8 weeks.The primary endpoint was the healing of peptic ulcers.Results The ulcer healing rate was 79.4％ (54/68) in the aspirin group and 84.3％ (59/70) in the placebo group.There was no statistically significant difference between the two groups (x2 =0.552,P ＞ 0.05).There were 5 cases of ulcer bleeding in aspirin group and placebo group.The rehaemorrhage rate was 7.4％ (5/68) and 7.1％ (5/70),respectively.There was no statistically significant difference between the two groups(x2 =0.002,P ＞ 0.05).Among the factors affecting the healing of aspirin-associated peptic ulcer,the healing rate was significantly associated with steroid use during treatment (x2 =6.135,P =0.041) and smoking status (x2 =5.616,P =0.018).Other factors,including age,hypertension,diabetes,alcohol history,history of previous ulcer bleeding,initial Helicobacter pylori status,and ulcer location did not affect ulcer healing.Conclusion After aspirin-associated peptic ulcer bleeding,continued low-dose aspirin plus rabeprazole did not affect the healing of peptic ulcers,and the use of steroids and smoking status are independent risk factors for ulcer healing.
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Objective To explore the effect of transcatheter hepatic artery chemoembolization(TACE)between different types of liver cancer patients with portal vein tumor thrombus(PVTT).Methods 413 liver cancer patients with PVTT were divided into two groups,TACE(332 cases)group and control group(81 cases);To compare the survival rate and the curative effect of two group.Results Survival rate in the TACE group of 3 months,6 months,12 months,24 months were 93.4%,71.7%,44.9%,24.4%,in the control group 3 months,6 months,12 months,24 months survival rate were 24.7%,2.5%,0,0.The difference has statistical significance(P＜0.01).In the TACE group,type Ⅰ,Ⅱ,Ⅲ,Ⅳ of PVTT patients treatmented with TACE also has different survival rate and different curative effect(P＜0.01).Conclusion TACE treatment is particularly effective for type Ⅰ,type Ⅱ and type Ⅲ patients of PVTT.