Hepatotoxicity of cantharidin is associated with the altered bile acid metabolism

Cantharidin (CTD) is an effective antitumor agent. However, it exhibits significant hepatotoxicity, the mechanism of which remains unclear. In this study, biochemical and histopathological analyses complemented with ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS)-based targeted metabolomic analysis of bile acids (BAs) were employed to investigate CTD-induced hepatotoxicity in rats. Sixteen male and female Sprague–Dawley rats were randomly divided into two groups: control and CTD (1.0 mg/kg) groups. Serum and liver samples were collected after 28 days of intervention. Biochemical, histopathological, and BA metabolomic analyses were performed for all samples. Further, the key biomarkers of CTD-induced hepatotoxicity were identified via multivariate and metabolic pathway analyses. In addition, metabolite–gene–enzyme network and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to identify the signaling pathways related to CTD-induced hepatotoxicity. The results revealed significantly increased levels of biochemical indices (alanine aminotransferase, aspartate aminotransferase, and total bile acid). Histopathological analysis revealed that the hepatocytes were damaged. Further, 20 endogenous BAs were quantitated via UHPLC-MS/MS, and multivariate and metabolic pathway analyses of BAs revealed that hyocholic acid, cholic acid, and chenodeoxycholic acid were the key biomarkers of CTD-induced hepatotoxicity. Meanwhile, primary and secondary BA biosynthesis and taurine and hypotaurine metabolism were found to be associated with the mechanism by which CTD induced hepatotoxicity in rats. This study provides useful insights for research on the mechanism of CTD-induced hepatotoxicity.     

The role of extra-hepatic bile duct resection in the surgical management of gallbladder carcinoma. A first meta-analysis

ObjectiveTo systematically evaluate the clinicopathological and prognostic value of extra-hepatic bile duct resection (EHBDR) in the surgical management of patients with gallbladder carcinoma (GBC), especially in non-jaundiced patients.MethodsPubMed, EMBASE and the Cochrane Library were searched up to March 1^st 2021 for comparative studies between bile duct resected and non-resected groups. RevMan5.3 and Stata 13.0 software were used for the statistical analyses.ResultsEHBDR did not correlate with a better overall survival (OS) (P = 0.17) or disease-free survival (P = 0.27). No survival benefit was also observed in patients with T2N1 (P = 0.4), T3N0 (P = 0.14) disease and node-positive patients (P = 0.75), rather, EHBDR was even harmful for patients with T2N0 (P = 0.01) and node-negative disease (P = 0.02). Significantly higher incidences of recurrent disease (P = 0.0007), postoperative complications (P < 0.00001) and positive margins (P = 0.02) were detected in the bile duct-resected group. The duration of postoperative hospital stay between the two groups was comparable (P = 0.58). Selection bias was also detected in our analysis that a significantly higher proportion of advanced lesions with T3-4 or III-IV disease was observed in the bile duct-resected group (P < 0.00001). EHBDR only contributed to a greater lymph yield (P = 0.01).ConclusionEHBDR has no survival advantage for patients with GBC, especially for those with non-jaundiced disease. Considering the unfairness of comparing OS between jaundiced patients receiving EHBDR with non-jaundiced patients without EHBDR, we could only conclude that routine EHBDR in non-jaundiced patients is not recommended and future well-designed studies with more specific subgroup analyses are required for further validation.     

Total bilirubin independently predicts incident metabolic syndrome among community-dwelling women

BackgroundMetabolic syndrome (MetS) is related to the increased risk of major cardiovascular diseases (CVD). The link between high serum total bilirubin (TBL) is cross-sectionally related to MetS and its components. However, whether serum TBL predicts incidence of MetS and its components remains inconclusive.MethodsThe present study included 893 women aged 70 ± 9 years from a rural village. We examined the relationship between serum TBL and MetS based on the modified criteria of the National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP) III report in a cross-sectional (N = 893) and cohort (N = 288) data.ResultsIn the cross-sectional study, serum TBL (β = 0.536, p < 0.001) as well as age, alcohol consumption, exercise habits, history of CVD, SUA, GGT, and ALT was significantly and dependently associated with number of MetS components, but in the cohort study serum TBL was not associated with number of MetS components. Compared with the 1st tertile of serum TBL (0.20–0.55 mg/dL), multivariate-adjusted odds ratio (95% confidence interval) for the 2nd -3rd tertiles of serum TBL (0.54–2.00 mg/dL) was 0.70 (0.51–0.95) in the cross-sectional study and 0.41 (0.21–0.81) in the cohort study.ConclusionsOur data demonstrated an independently negative association between serum TBL and MetS in Japanese community-dwelling women.     

Curcumin ameliorates hepatic chronic inflammation induced by bile duct obstruction in mice through the activation of heme oxygenase-1

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Mildly decreased preoperative bilirubin levels are associated with infections after shoulder and knee arthroplasty

Increasing numbers of arthroplasties are also accompanied by postoperative infections. The main purpose was to evaluate preoperative serum bilirubin levels between patients with and without infections after shoulder and knee arthroplasties. For this retrospective case-control single-center study, a total of 108 patients were extracted from a prospectively collected database. Eighteen patients with infections after shoulder (n = 8) and knee (n = 10) arthroplasty were matched by age, gender, and implant type in a 1:5-scenario to 90 patients (40 shoulders and 50 knees) without postoperative infection. Demographic data, preoperative blood parameters, and postoperative infection-related outcomes were evaluated. Total bilirubin was the only preoperative parameter significantly different between the infection (8.21 ± 3.25 μmol/L or 0.48 ± 0.19 mg/dL) and noninfection (10.78 ± 4.62 μmol/L or 0.63 ± 0.27 mg/dL; P = .014) group, while C-reactive protein and other liver parameters were similar between the groups. Significantly more controls (92.1%) had preoperative bilirubin levels above 8.72 μmol/L or 0.51 mg/dL than cases (7.9%; P = .007). The 5-year infection survival-rate was 65.6% for patients with preoperative bilirubin levels < 8.72 μmol/L or < 0.51 mg/dL and 91.2% with ≥ 8.72 μmol/L or ≥ 0.51 mg/dL. Mildly decreased preoperative bilirubin levels with a cutoff at 8.72 μmol/L or 0.51 mg/dL were significantly associated to patients with infections after shoulder and knee arthroplasty. There were no differences in other blood parameters or comorbidities between patients with infections and their matched-controls.     

十二指肠镜治疗胆总管结石35例临床分析

目的探讨经十二指肠镜治疗胆总管结石的临床效果和价值。方法经十二指肠镜治疗胆总管结石共35例,其中行EST及取石术32例,行EPBD及取石术3例。EST胆总管取石时根据结石大小决定切开大小,不宜EST或结石较小者可选择EPBD后取石。结果35例均成功取出胆总管结石,取得较好的疗效。EST术中局部渗血4例,当时予电凝或喷洒止血药物即迅速止血,术后急性胰腺炎1例,经适当处理后1周痊愈,EPBD及取石术后未发现明显并发症。结论十二指肠镜治疗胆总管结石是一种微创、安全、有效的治疗方法。     

The case for laparoscopic common bile duct exploration

The modern surgeon's approach to choledocholithiasis depends his or her view of cholangiography. During the early 1990 there was a swing away from cholangiography, which had previously been common practice. This was because of perceptions of difficulty with the technique, the time it took, and perhaps an implied increase in costs because of the time factor. There was no evidence on which to base this decision. This led to a marked upswing in the use of endoscopic retrograde cholangiopancreatography (ERCP). There were a large number of ERCPs with normal results performed prior to laparoscopic cholecystectomy. This paper states the case for intraoperative cholangiography and common bile duct clearance at the time of cholecystectomy. It is hoped that this technique will be adopted so patients can undergo a single procedure to remove their gallstones and common bile duct stones if they exist and to decrease the incidence of normal preoperative ERCPs and the need for a second procedure postoperatively to clear stones if they are found.     

旋磁场对胆结石病人胆汁中胆红素、钙、胆固醇和pH的影响

目的 探讨旋磁场与大面积静磁场对置对胆结石病人胆汁中总胆红素（BIT）、直接胆红素（BID）、间接胆红素（BII）、钙（Ca）、胆固醇（CH）和pH的影响。方法 旋磁组30例,测定旋磁处理前后65对胆汁样本。空白对照组15例,留取前后30对胆汁样本。将直径12mm圆形稀土永磁片110块,表面磁感应强度210mT,分别间隔10mm贴于210mm×220mm铁皮上形成一个大面积磁板与旋磁头表面静磁感应强度160mT,旋转平均表面磁感应强度100mT呈异名极对置,磁板置肝区背侧,旋磁头置剑突下处理40min。结果 旋磁组胆结石病人胆汁（n=65）:经旋磁场与磁板对置处理前减去处理后差值的x±s和t值分别为BIT41.81±93.52、3.59;BID 13.57±43.70、2.46;BII28.27±61.67、3.32;Ca 0.19±0.31、4.87;CH0.12±0.29、3.36;pH 0.01±0.27、0.30。除pH外,其余各项指标P值均<0.05。对照组胆汁（n=30）:间隔时间前后差值的x±s和t值分别为BIT4.42±22.05、1.14;BID2.40±12.37、1.06;BII2.52±46.27、0.30;Ca0.01±0.18、0.50;CH0.03±0.15、0.94;pH 0.009±0.06、0.84。P值均>0.05。结论 在本项磁场类型、强度和时间处理条件下,旋磁场与磁板对置能明显影响胆结石病人胆汁中的BIT、BID、BII、Ca和CH的浓度变化,且有显著降低的作用。