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.     

伊伐布雷丁在心血管疾病中的现状与进展

降低心率可能成为心血管疾病治疗的新靶标,伊伐布雷定可通过特异性地抑制If起搏电流通过降低窦房结节律而减慢心率,目前在心血管疾病领域取得了一定的进展,现对其临床应用进行综述。     

针刺配合肠炎散保留灌肠治疗肛窦炎临床研究

目的观察肛窦炎应用针刺配合肠炎散保留灌肠治疗的效果。方法选取2017年10月-2018年10月就诊的72例肛窦炎患者,采用随机数字表法分为观察组(n=36)与对照组(n=36)。对照组给予肠炎散保留灌肠治疗,观察组为针刺配合肠炎散保留灌肠治疗,比较2组症状、疗效及安全性。结果观察组症状(放射痛、指诊症状及镜检症状)少于对照组,总有效率高于对照组,差异有统计学意义(P<0.05);2组安全性相比,差异无统计学意义(P>0.05)。结论针对肛窦炎患者,予以针刺配合肠炎散保留灌肠治疗效果确切,可减少临床症状,加快疾病转归,且治疗安全性较好。     

Altered central micro-opioid receptor binding after psychological trauma.

BACKGROUND: Functional neuroimaging studies have detected abnormal limbic and paralimbic activation to emotional probes in posttraumatic stress disorder (PTSD), but few studies have examined neurochemical mechanisms that underlie functional alterations in regional cerebral blood flow. The mu-opioid neurotransmitter system, implicated in responses to stress and suppression of pain, is distributed in and is thought to regulate the function of brain regions that are implicated in affective processing. METHODS: Here we examined the micro-opioid system with positron emission tomography and the micro-opioid receptor-selective radiotracer [11C] carfentanil in 16 male patients with PTSD and two non-PTSD male control groups, with (n = 14) and without combat exposure (n = 15). Differences in micro-opioid receptor binding potential (BP2) were detected within discrete limbic and paralimbic regions. RESULTS: Relative to healthy controls, both trauma-exposed groups had lower micro-opioid receptor BP2 in extended amygdala, nucleus accumbens, and dorsal frontal and insular cortex but had higher BP2 in the orbitofrontal cortex. PTSD patients exhibited reduced BP2 in anterior cingulate cortex compared with both control groups. Micro-opioid receptor BP2 in combat-exposed subjects without PTSD was lower in the amygdala but higher in the orbitofrontal cortex compared with both PTSD patients and healthy controls. CONCLUSIONS: These findings differentiate the general response of the micro-opioid system to trauma from more specific changes associated with PTSD.     

Incidence of Type 2 diabetes in England and its association with baseline impaired fasting glucose: the Ely study 1990-2000.

AIM: To determine the incidence of Type 2 diabetes and to examine the effect of different cut-points for impaired fasting glucose (IFG) on diabetes incidence. METHODS: Population-based longitudinal study (1990-2000) with clinical, anthropometric and biochemical measurements, including an oral glucose tolerance test (OGTT), in 1040 non-diabetic adults aged 40-69 years at baseline. Baseline glucose status was defined as normoglycaemia < 5.6, IFG-lower 5.6-6.0 and IFG-original 6.1-6.9 mmol/l. The all-IFG group included fasting glucose values of 5.6-6.9 mmol/l. RESULTS: The 10-year cumulative incidence of diabetes was 7.3 per 1000 person-years. Diabetes incidence was 2.4 [95% confidence interval (CI) 1.2, 4.8], 6.2 (4.0, 9.8) and 17.5 (12.5, 24.5) per 1000 person-years in those with normoglycaemia, IFG-lower and IFG-original, respectively. Compared with normoglycaemia, the age/sex-adjusted risk [hazard ratio (HR) and 95% CI] for incident diabetes was greatest in the IFG-original category (HR 6.9; 3.1, 15.2) and increased to a lesser degree in the IFG-lower (HR 2.5; 1.1, 5.7) and all-IFG categories (HR 4.1; 1.9, 8.7). When adjusted for confounding factors, the magnitude and direction of associations persisted, with HR 1.9, 4.4 and 2.9, for the categories IFG-lower, IFG-original and all-IFG, respectively. CONCLUSIONS: Diabetes incidence is more strongly related to IFG defined as fasting glucose between 6.1 and 6.9 mmol/l than to the lower category of 5.6-6.0 mmol/l, or entire range of 5.6-6.9 mmol/l. Future studies should examine the association of IFG with cardiovascular outcomes, but for diabetes risk our study supports the use of the IFG cut-point at 6.1 mmol/l.     

维甲酸硅油的视网膜毒性实验研究

目的：了解维甲酸硅油对视网膜是否产生毒性。 方法：12只新西兰白兔的24只眼，随机分为3组，行气体压迫玻璃体手术3天后，分别向玻璃体腔内注入硅油(4只眼)、5μg/ml维甲酸硅油(10只眼)、10μg/ml维甲酸硅油(10只眼)各
0.5m1，用检眼镜、光漳和电镜检查来观察视网膜变化情况。 结果：注入硅油28天后，未发现各浓度的维甲酸硅油对视网膜产生毒性作用。结论：浓度为5、10μg/ml的维甲酸硅油注入玻璃体腔4周，对视网膜不产生毒性作用。 （中华眼底病杂志，1997，13：81-82）     

青蒿知母汤治疗恶性肿瘤长期发热34例

恶性肿瘤患者发热较为常见,其发生有多方面的原因.临床上多使用糖皮质激素或非甾类解热镇痛消炎药治疗,有一定疗效但不良反应多.我们使用自制青蒿知母口服液治疗恶性肿瘤患者发热,取得满意疗效,现报道如下.     

Triptolide inhibits T cell activation and proliferation via multiple pathways

Triptolide is potent immunosuppressive has been reported to inhibit autoimmunity, compound isolated from Chinese herbal medicine. Triptolide allograft attributed to the suppression of T cells via NF - kB rejection and GVHD, and its efficacy was previously pathway and apoptosis. In the present study, we detailedly analyzed Triptolide＇ s function on murine primary T cell. We found that Triptolide could inhibit T cell activation and proliferation by dramatically down - regulating cell division and cell cycle. Triptolide inhibited T cell activation in a dose- dependent manner, and the inhibition was mediated by both NF- kB pathway and AP - 1 pathway.