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.     

Acute toxicity of chlorpyrifos to the non-target organism Cnesterodon decemmaculatus

Chlorpyrifos is the most used insecticide in Argentina. Cnesterodon decemmaculatus is a widely distributed, endemic fish from Neotropical America. It attains high densities in the shallow water assemblages of Argentina and Brazil. The aim of this study was to assess the acute toxicity of chlorpyrifos to C. decemmaculatus. The mean 96-h LC₅₀ of three independent determinations was 105.3 (±?3.1) μg/L. Sublethal effects were observed. Swimming behavioral changes at each chlorpyrifos exposure concentration were reported. C. decemmaculatus represents a good model for ecotoxicological risk assessment.     

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

1. Download : Download high-res image (66KB)
2. Download : Download full-size image

     

急性CO中毒迟发性脑病患者早期血浆HMGB1的表达与预后

目的：探讨急性一氧化碳(CO）中毒迟发性脑病患者血浆高迁移率族蛋白B1(HMGB1）的表达与预后。方法回顾性分析2012年1月—2015年1月该院接收的最终确诊为急性CO中毒迟发性脑病患者10例，另选取同时期内急性CO中毒患者10例以及健康体检者10例作为对照组。分别对各组患者的血浆HMGB1水平进行检测。另外，分别采用日常生活能力量表(ADL）、常识-记忆-注意测验(IMCT）、长谷川痴呆量表(HDS）分析急性CO中毒迟发性脑病患者血浆HMGB1水平变化及与量表评分之间的关系。结果 CO中毒迟发性脑病患者急性期血浆HMGB1水平为(14.23±10.32）ng/mL，明显高于恢复期的(7.93±4.99）ng/mL，差异有统计学意义(t=2.653，P<0.05）；CO中毒迟发性脑病组急性期、恢复期血浆HMGBl水平与HDS以及ADL评分呈现显著正相关(r=0.610；r=0.605；r=0.607；r=0.610,P<0.05）。结论HMGBl参与急性CO中毒迟发性脑病的炎症反应前过程，且与HDS以及ADL评分呈正相关。     

Acute liver injury,acute liver failure and acute on chronic liver failure: A clinical spectrum of poisoning due to Gyromitra esculenta

Gyromitra esculenta, also known as “false morel” is one of the most poisonous mushrooms. This species is found all over the world, growing in coniferous forest in early spring time. Common manifestation of poisoning includes gastrointestinal symptoms which include varied degrees of liver impairment.We describe three cases: acute liver injury, acute liver failure and acute-on-chronic liver failure due to G. esculenta poisoning. At admission patients presented with encephalopathy and features of liver failure. Two of them recovered completely following supportive management while the remaining patient who also had preexisting liver disease developed multiorgan failure and subsequently died.Although a rare occurrence, G. esculenta poisoning should be considered in the differential diagnosis of acute liver failure.     

腹腔镜胆总管切开探查取石46例报告

目的探讨腹腔镜胆总管切开探查取石、胆总管一期缝合的可行性及其微创价值。方法回顾分析我院46例腹腔镜胆总管切开探查取石的临床资料。腹腔镜下完成手术44例,其中胆总管切开探查取石胆总管一期缝合24例,胆总管切开探查取石胆总管T管引流20例;中转开腹胆总管切开取石T管引流2例。结果手术中无副损伤。手术后无胆漏及其它并发症发生。所有病例是治愈出院。32例术后随访3～12个月,未发现残余结石及胆道狭窄。结论腹腔镜胆总管切开探查取石、胆总管一期缝合是可行的,而且具有极大的微创优势。     

急性一氧化碳中毒后迟发性脑病的临床表现和影像学特点

目的探讨急性一氧化碳中毒后迟发性脑病的临床表现和影像学特点及其诊断价值。方法回顾性对23例急性一氧化碳中毒后迟发性脑病的临床表现和影像学特点进行归纳和分析。结果23例患者中智能障碍23例（100％），言语功能障碍17例（73.9％），另有共济失调精神障碍帕金森综合症及尿失禁等。头部CT和MRI主要表现为皮层下脑白质异常信号及基底节区或苍白球区异常信号，极少累及大脑皮质脑干和小脑。结论急性一氧化碳中毒后迟发性脑病的诊断主要依靠病史和临床症状，MRI比CT更有诊断价值。