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【Objective】 To observe the therapeutic effects of Axitinib, a tyrosine kinase receptor inhibitor, on liver fibrosis. 【Methods】 In vivo, CCL4 was injected intraperitoneally to induce liver fibrosis in mice. After modeling, Axitinib-carboxymethyl cellulose (Axitinib-CMC) solution or CMC solution were administered by gavage. After 2 weeks of modeling, 4 weeks of modeling, 1 week of treatment and 2 weeks of treatment, the mice were killed and their liver tissues were stained by HE, Masson and α - SMA immunohistochemistry. In vitro, human hepatic stellate cell line (LX2) and human normal liver cell line (LO2) were intervened with different concentrations of Axitinib-CMC solution. MTT assay was performed 48 h and 72 h after the intervention. Flow cytometry was used to observe the apoptosis of the two cell lines. Western blotting was used to detect the expressions of Fas, Caspase-8, Caspase-3 and Bcl-2 proteins. 【Results】 HE and Masson staining results showed that CCL4 could induce liver fibrosis in the mice, and the degree of liver fibrosis was more severe in the 4-week than that in the 2-week treatment group. After treatment with Axitinib, the collagen staining area and the positive expression level of α-SMA were significantly lower than those in 4-week group and CMC treatment control group (P<0.05). In vitro, Axitinib could effectively inhibit the viability of hepatic stellate cell line LX2 and promote its apoptosis. Meanwhile, the expressions of pro-apoptotic proteins Fas, Caspase-8 and Caspase-3 increased, while the expression of apoptosis suppressor gene Bcl-2 decreased. However, the above changes were not found in control hepatocyte line LO2. 【Conclusion】 Axitinib exerts an anti-fibrosis effect by inducing apoptosis of hepatic stellate cells, and has no significant effect on normal hepatocytes.
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Objective:To predict the efficacy and safety of cephalosporins antibiotics combined with metronidazole for intra-abdominal infections using Bayesian network meta analysis.Methods:Databases including PubMed, Embase, the Cochrane Library, CNKI, Wanfang database, VIP database were searched for literatures from January 1990 to May 2018 with the key words of ( "intraabdominal infections" [MeSH Terms]) AND ( "Cephalosporins*" [MeSH Terms]) AND ( "randomized controlled trial" [MeSH Terms]),腹腔感染,继发性腹膜炎,腹腔脓肿,头孢. The randomized controlled trials (RCTs) about comparison of efficacy and safety between cephalosporins antibiotics combined with metronidazole versus other antibiotics for intra-abdominal infections were received and included. Experimental group included patients who received cephalosporins antibiotics combined with metronidazole for intra-abdominal infections, and control group included patients who received other antibiotics for intra-abdominal infections. The primary outcomes were the clinical cure rates, microbial clearance rate and incidence of serious adverse drug reactions. R 3.6.2 software random Bayesian model was used for meta analysis. The Markov Chain Monte Carlo was used for direct evaluation and indirect prediction. The tracing method, density plotting and leverage figure method were used to evaluate the model convergence and stability. No closed loop formed between intervention measures, so there was no need to evaluate consistency.Results:(1) Document retrieval: a total of 18 available RCTs were enrolled. There were 6 792 patients, including 3 402 in the experimental group, 3 390 in the control group. (2) Results of Bayesian network meta analysis. ① The clinical cure rates of the third generation cephalosporins+ metronidazole, carbapenems were significantly lower than the fourth generation cephalosporins+ metronidazole [ odds ratio ( OR)=0.46, 0.61, 95% confidence interval( CI) as 0.26-0.81, 0.38-0.97, P<0.05]. There was no significant difference in the clinical cure rate between the fifth generation cephalosporins+ metronidazole and carbapenems ( OR=1.03, 95% CI as 0.59-1.80, P>0.05). ② The microbial clearance rates of the fifth generation cephalosporins+ metronidazole, carbapenems were significantly lower than the fourth generation cephalosporins+ metronidazole ( OR=0.84, 0.41, 95% CI as 0.73-0.98, 0.23-0.74, P<0.05). There was no significant difference in the microbial clearance rate between the fifth generation cephalosporins+ metronidazole and carbapenems ( OR=0.76, 95% CI as 0.27-1.80, P>0.05). ③ The incidence of serious adverse drug reactions was significantly lower for the third generation cephalosporins+ metronidazole, the fourth generation cephalosporins antibiotics+ cetronidazole, the fifth generation cephalosporins+ metronidazole, carbapenems, quinolones+ metronidazole, and tigecycline than for quinolones ( OR=0.13, 0.13, 0.14, 0.13, 0.15, 0.13, 95% CI as 0.03-0.50, 0.02-0.98, 0.02-0.75, 0.02-0.59, 0.02-0.78, 0.02-0.57, P<0.05). Compared with carbapenems, the third generation cephalosporins+ metronidazole, the fourth generation cephalosporins+ metronidazole, the fifth generation cephalosporins+ metronidazole had no significant difference in the incidence of serious adverse drug reactions ( OR=0.96, 1.00, 1.10, 95% CI as 0.52-1.60, 0.31-3.50, 0.49-2.30, P>0.05). (3) Ranking of the efficacy and safety. ① The ranking list for clinical cure rates of different therapeutic regimens showed from high to low as quinolones+ metronidazole, the fourth generation cephalosporins+ metronidazole, synthetic penicillins, the second generation cephalosporins+ metronidazole, the fifth generation cephalosporins+ metronidazole, carbapenems, the third generation cephalosporins+ metronidazole, tigecycline, quinolones. The corresponding ranking probabilities of above regimens were 51.73%, 35.72%, 22.57%, 31.37%, 24.98%, 32.82%, 34.69%, 29.05%, 72.36%, respectively. ② The ranking list for microbial clearance rates of different therapeutic regimens showed from high to low as quinolones+ metronidazole, the fourth generation cephalosporins+ metronidazole, the second generation cephalosporins+ metronidazole, synthetic penicillins, the fifth generation cephalosporins+ metronidazole, carbapenems, the third generation cephalosporins+ metronidazole, tigecycline, quinolones. The corresponding ranking probabilities of above regimens were 89.62%, 77.01%, 38.60%, 20.94%, 26.26%, 26.39%, 22.22%, 20.19%, 62.55%, respectively. ③ The ranking list for incidence of serious adverse drug reactions of different therapeutic regimens showed from high to low as quinolones, quinolones+ metronidazole, the fifth generation cephalosporins+ metronidazole, carbapenems, the third generation cephalosporins+ metronidazole, tigecycline, the fourth generation cephalosporins+ metronidazole. The corresponding ranking probabilities of above regimens were 96.21%, 30.46%, 21.09%, 25.27%, 27.26%, 19.45%, 31.69%, respectively. Conclusion:In the treatment of middle- and low-risk intra-abdominal infections, it is recommended to empirically use cephalosporins+ metronidazole instead of carbapenems.
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Objective:To investigate the risk factors of portal vein system thrombosis (PVST) after portoazygous devascularization in patients with portal hypertension.Methods:Clinical data of 215 patients with portal hypertension treated by splenectomy at the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi′an Jiaotong University from Jan 2012 to Dec 2017 were retrospectively analyzed. Univariate analysis of variance and Logistic regression were used to analyze the clinical risk factors that may lead to PVST.Results:The incidence of PVST was 43.7%(94/215). Univariate analysis of variance showed that the diameter of portal vein, the diameter of splenic vein, the thickness of spleen, laparoscopic or open surgery, and postoperative platelet count were correlated with postoperative PVST (all P<0.05). Logistic regression analysis showed that splenic vein diameter ( OR=3.137, 95% CI 1.391-7.076, P=0.006), splenic thickness ( OR=3.065, 95% CI 1.418-6.626, P=0.004) and postoperative platelet count ( OR=7.446, 95% CI 3.057-18.137, P=0.000) were independent risk factors for PVST in patients with portal hypertension. Conclusion:Postoperative PVST in patients with portal hypertension are more likely to develope when preoperative splenic vein ≥11 mm, splenic thickness ≥60 mm and platelet count ≥300×10 9/L on the 7th day after operation.