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.     

改良三点式重睑成形术的临床应用研究

目的:探讨改良三点式重睑术的临床应用疗效。方法:2012年6月-2019年6月,共165例单睑患者采用了改良三点式重睑术,沿术前标记线将三点处皮肤切开,剪刀将切口下唇的眼轮匝肌适当去除,同时将切口与切口在皮下层打通,剪除切口与切口之间的眼轮匝肌,6-0可吸收线挂睑板前筋膜或提上睑肌腱膜及切口下唇皮下组织缝合,三点切口各缝1针。再用6-0单丝尼龙线按照常规重睑线缝合方法挂切口下唇皮肤、睑板前筋膜或提上睑肌腱膜及切口上唇皮肤缝合打结,三点切口各缝1针。伴内眦赘皮者同时行内眦赘皮矫正术。结果:152例患者获得随访,随访患者大部分获得了比较满意的重睑,睁眼重睑流畅、自然,闭眼刀口痕迹不明显。2例患者出现内侧重睑线变浅,1例患者出现外侧重睑线变浅,所有患者均未出现重睑消失。5例患者双侧重睑线有轻度不对称。患者总体满意率为94.7%(144/152)。结论:改良三点式重睑术具有创伤小、并发症少、效果逼真、不易脱落、手术痕迹不明显等优点,值得推广应用。     

Myeloid-derived suppressor cell (MDSC) key genes analysis in rat anti-CD28-induced immune tolerance kidney transplantation

BackgroundIn the field of transplantation, inducing immune tolerance in recipients is of great importance. Blocking co-stimulatory molecule using anti-CD28 antibody could induce tolerance in a rat kidney transplantation model. Myeloid-derived suppressor cells (MDSCs) reveals strong immune suppressive abilities in kidney transplantation. Here we analyzed key genes of MDSCs leading to transplant tolerance in this model.MethodsMicroarray data of rat gene expression profiles under accession number {"type":"entrez-geo","attrs":{"text":"GSE28545","term_id":"28545"}}GSE28545 in the Gene Expression Omnibus (GEO) database were analyzed. Running the LIMMA package in R language, the differentially expressed genes (DEGs) were found. Enrichment analysis of the DEGs was conducted in the Database for Annotation, Visualization and Integrated Discovery (DAVID) database to explore gene ontology (GO) annotation and their Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Their protein-protein interactions (PPIs) were provided by STRING database and was visualized in Cytoscape. Hub genes were carried out by CytoHubba.ResultsThree hundred and thirty-eight DEGs were exported, including 27 upregulated and 311 downregulated genes. The functions and KEGG pathways of the DEGs were assessed and the PPI network was constructed based on the string interactions of the DEGs. The network was visualized in Cytoscape; the entire PPI network consisted of 192 nodes and 469 edges. Zap70, Cdc42, Stat1, Stat4, Ccl5 and Cxcr3 were among the hub genes.ConclusionsThese key genes, corresponding proteins and their functions may provide valuable background for both basic and clinical research and could be the direction of future studies in immune tolerance, especially those examining immunocyte-induced tolerance.     

阿戈美拉汀联合乙哌立松治疗青年慢性紧张性头痛的疗效分析

目的 探讨阿戈美拉汀联合乙哌立松治疗青年慢性紧张性头痛(Chronictention-typeheadache,CTTH)的疗效及安全性.方法 80例青年慢性紧张性头痛患者依据是否倒班随机分为对照组和治疗组,对照组口服乙哌立松治疗,治疗组在对照组基础上联合阿戈美拉汀治疗,评估2组患者治疗前匹兹堡睡眠量表评分(PSQI)评估治疗6周后两组的头痛疗效以及不良反应.结果 倒班人员的入组前PSQI的总评分、睡眠质量、入睡时间、催眠药物及睡眠障碍因子分高于非倒班人员;治疗组的疗效优于对照组,有统计学意义(P＜0.05);治疗组内,倒班患者疗效优于非倒班患者(P＜0.05).两组不良反应无明显差异.结论 阿戈美拉汀联合乙哌立松治疗慢性紧张性头痛的的疗效确切,安全性高.