Astragalus membranaceus ultrafine powder alleviates hyperuricemia by regulating the gut microbiome and reversing bile acid and adrenal hormone biosynthesis dysregulation

Ethnopharmacological relevanceMetabolic syndrome is closely related to the intestinal microbiota and disturbances in the host metabolome. Hyperuricemia (HUA), a manifestation of metabolic syndrome, can induce various cardiovascular diseases and gout, seriously affecting a patient’s quality of life. Astragalus membranaceus has a long history as a commonly used traditional Chinese medicine to treat kidney disease in China and East Asia.Materials and methodsWe compared the therapeutic effect of benzbromarone and two different doses Astragalus membranaceus ultrafine powder (AMUP) in rats with HUA. Ultra-performance liquid chromatography-mass spectrometer was used to analyze the AMUP metabolism in the plasma, urine, and feces. Further, 16S ribosome RNA sequencing and feces metabolomic were performed to capture the variation of the gut microbiota and metabolites changes before and after drug administration.ResultsAMUP had a notable impact on reducing blood uric acid levels while protecting the liver and kidney. Drug metabolism analysis demonstrated that effective constituent flavonoids are distributed in the blood, whereas saponins remain in the intestine. Gut microbiota analysis showed that low-dose AMUP ameliorated HUA-induced gut dysbiosis by reducing the abundance of harmful bacteria and increasing that of some beneficial bacteria with anti-inflammatory properties, such as Clostridia, Lachnospiraceae, and Muribaculaceae. In addition, HUA-induced changes in metabolite contents in bile acid and adrenal hormone biosynthesis pathways were restored after treatment with AMUP.ConclusionLow-dose AMUP exerts remarkable therapeutic effects on HUA by regulating the gut microbiome and mediating gut metabolism pathways associated with uric acid excretion.     

含离子液体［bmim］Cl的反应介质中马肝醇脱氢酶的催化特性

 研究了马肝醇脱氢酶(HLADH)在含离子液体1-丁基-3-甲基咪唑氯酸盐(［bmim］Cl)的反应介质中的催化特性. 以乙醇为底物时,该酶在［bmim］Cl含量≤0.15 g/ml的体系中的活力高于在不含离子液体的体系中的活力; 离子液体浓度过高(＞0.15 g/ml)对酶活性有明显的抑制作用. 反应温度和pH对含离子液体的反应介质中酶活力的影响规律与不含离子液体时的规律相似. 与不含离子液体的反应介质相比, HLADH在含0.05 g/ml ［bmim］Cl的体系中催化乙醇氧化的活化能下降,酶反应的Vmax和Km均升高. 反应体系中低浓度(≤0.1 g/ml)的离子液体能提高酶的热稳定性,但高浓度(＞0.1 g/ml)的离子液体可降低酶的热稳定性. 紫外二阶导数光谱显示,在含不同浓度离子液体的反应介质中酶分子构象的变化有较大的差异.     

Saccharide-branched Cyclodextrins as Targeting Drug Carriers

A synthetic series of heptakis-galactose-branched cyclodextrins (termed CDs) having a longer spacer arm using two amino-caproic acids as an enlarging unit were prepared. Starting with heptakis-amino-β-CD or heptakis-amino-caproic-amide-β-CD, treated with galactosyl-glucono-amide-caproic acid, the new compounds heptakis (Gal-cap1)-CD (4) or heptakis (Gal-cap2)-CD (5) were obtained. The longer galactose spacer arm extremely favors the PNA association. The effect of branch length on K with PNA was enhanced up to 138-fold 3 as well as with DXR enhanced up to 81-fold. Hexakis (Gal-cap2)-CD (6) was prepared and the association constants with rat liver cells were observed to be 2.5 × 10¹⁰ M⁻¹. A multi-high mannose type oligosaccharide branched CD (7) showed a large association constant with DXR up to 1.1 × 10⁹ M⁻¹. The two-dimensional map for the association constants of newly synthesized oligosaccharide-branched CDs toward lectin or liver cells versus the association constants toward a drug (doxorubicin) suggested a method of finding a better targeting drug carrier. The structural effect of the oligosaccharide-CDs showed that the number and length of the branch were dominant factors in designing for enhanced dual recognition.     

抗肝纤维化药物研究现状

肝纤维化是肝硬化的早期阶段，是慢性肝病向肝硬化发展的必经途径，也是各种慢性肝病的共同病理过程，因此阻断肝纤维化的发生和发展具有重要意义．所以人们对抗肝纤维药物的研究十分重视．本文将简要综述近年来对肝纤维化药物的一些新认识和新进展．     

无关供者骨髓移植治疗多次复发性急性白血病

文章探讨无关供者骨髓移植治疗多次复发急性白血病的疗效 .经改良 Bucy方案预处理后对一例第三次复发的急粒患者行无关供者骨髓移植 ,同时给防治 GVHD、抗感染治疗 .结果 + 2 1天骨髓在患者体内植活 ,+ 35天细胞染色体分析呈供者型 ( 4 6,XX.正常核型 ) ,+ 84天血型转换成供者型 ,至今已无病生存超过 6个月 .结果表明 ,无关供者骨髓移植对多次复发的急性白血病患者具有治疗价值     

肝病患者胰岛素样生长因子Ⅰ水平观察

探讨胰岛素样生长因子Ⅰ(IGF—Ⅰ)在各型肝病患者中的变化规律。用放射免疫法到定188例肝病急者50例正常人的血清IGF—Ⅰ含量。结果表明，肝硬化及肝癌患者的IGF—Ⅰ水平明显低于正常对照组(P＜0．01)。IGF—Ⅰ是在肝脏疾病的发展过程中判断肝细胞功能不良的重要指标。检到IGF—Ⅰ对肝病患者尤其是判断肝硬化进展情况有一定的意义。     

内固定加带血管肌蒂骨瓣移植治疗股骨颈骨折

目的:研究提高股骨颈骨折愈合率、降低股骨头坏死率的治疗手段 方法:采用切开复位、中空加压螺纹钉、骨圆针内固定加带旋股外侧动脉升支和阔筋膜张肌蒂髂骨瓣植骨治疗股骨颈移位骨折 结果:术后随访1～9年共46例,发生骨折不愈合3例、股骨头缺血坏死4例,其他无严重并发症 根据X光片和功能恢复情况分析:优24例(占52.17%)、良15例(占32.61%)、可3例(占6.52%)、差4例(占8.70%),功能恢复满意率为91.30% 结论:带旋股外侧动脉升支血管和阔筋膜张肌蒂髂骨瓣移植给缺血的股骨头引入血供,能促进股骨颈骨折愈合,减少股骨头缺血性坏死和骨折不愈合     

对中国移植近代以来西方法律制度的解释学反思

法律移植以理解为前提 ,理解是视域的融合 ;但中国传统文化的视域难与近代以来西方法律制度的视域融合 ,因为二者有着实质性差异 ;解决这一问题的方法是在中国培植近代以来西方法律制度所需要的文化生态环境———商业社会。     

经砷诱导人肝细胞L02获得砷耐受性的研究

砷是自然界普遍存在的毒性较强的类金属元素。几乎所有生物在进化中都产生了对砷毒性的耐受性。生物体对砷的耐受机制受到广泛关注。本实验采用低剂量(4μmol／L)NaAsO2诱导人体正常肝细胞株LO2,利用噻唑兰检测法(MTT)计算细胞生存率及半数致死量反映细胞对砷耐受性的改变，结果发现低剂量砷诱导6周后，在48h急性砷中毒试验中，实验组LC50为23．0μmol／L，对照组为11．9μmo1／L，实验组明显高于对照组，说明细胞对急性砷中毒耐受性明显提高。     

猪肝样品中莱克多巴胺测定的前处理方法

研究猪肝样品中莱克多巴胺测定的样品前处理方法。样品直接用HCl酸解并超声提取,同时添加70%~72%的高浓度HClO_4对酸解样品进行蛋白沉淀,然后经MCX固相萃取柱净化后,用液相色谱-串联质谱法检测。用正交试验考察了酸的种类、浓度、提取时间、提取温度和HClO_4体积对提取效率的影响,最佳条件为:HCl浓度为0.2mol/L,提取时间为40min,提取温度为25℃,HClO_4用量为200μL。从0.5、5.0和10.0μg/kg添加水平检测结果可以看出,方法平均回收率为82.0%~102%,日内和日间精密度4%,符合国家标准对检验方法的要求。该方法灵敏度高,精密度好,成本低,能简便、快速对样品中的莱克多巴胺进行提取,实现对动物源性食品的快速监测。