根据新版核查要点浅析某儿童医院临床试验质控常见问题

目的:分析与总结苏州大学附属儿童医院临床试验机构质控中发现的问题。 方法:按照国家药品监督管理局食品药品 审核查验中心最新发布的核查要点对 2021 年 1 月-2023 年 6 月机构质控报告中的问题进行整理与归类。 结果:本机构临床试 验项目质控中发现的问题主要集中在研究人员资质文件收集、知情同意书签署、异常值评判、试验数据记录等方面。 结论:临床 试验机构、伦理委员会、研究者和申办方均应履行各自职责,对试验质量全程把关,保障受试者的权益与安全、保证临床试验数 据的真实性。     

两种术式在缓解恶性输尿管梗阻疗效中的对比研究

目的 探讨恶性输尿管梗阻（malignant ureteral obstruction,MUO）现有的临床治疗方案和经验,讨论恶性输尿管梗阻时使用经皮肾脏穿刺引流（percutaneous nephrostomy,PN）或输尿管支架置入术（ureteral stenting,US）的临床适用范围,明确2种术式在缓解恶性输尿管梗阻时肾功能损伤的有效性。方法 回顾性纳入重庆医科大学附属第一医院泌尿外科2021年1月至2023年5月诊断为恶性输尿管梗阻的患者,严格筛选纳入及排除标准后共有76例患者入组并随机分为PN组（n=22）与US组（n=54）,对患者基本特征及围术期、术后半年随访数据进行病例对照研究以反映肾功能在2组中的差异,采用SPSS 21.0版本对数据进行处理分析。结果 2组患者在性别（P=0.017）、手术侧肾积水程度（P=0.000）的比较,差异有统计学意义。2组患者术前3 d比较尿素氮（P=0.002）、血肌酐（P=0.003）,术后1 d尿素氮（P=0.017）、血肌酐（P=0.005）,差异有统计学意义。术后3 d与术后6个月2组患者在肾功能比较中差异均无统计学意义。结论 恶性输尿管梗阻以宫颈癌多发,其次为位膀胱癌、结直肠癌等。US可选择梗阻或积水较轻、慢性输尿管梗阻、肾功能损伤较轻的患者,可作为缓解输尿管梗阻的首选治疗方案。PN临床常对中至重度肾积水、肾功能损伤较重或者急性肾功能不全的恶性输尿管梗阻患者进行治疗,可作为US失败的替代方案。     

Nanofused Hierarchically Porous MIL-101(Cr) for Enhanced Methyl Orange Removal and Improved Catalytic Activity

Hierarchically porous MIL-101(Cr) (H-MIL-101(Cr)) with meso/macro-pores was directly prepared via nanofusion progress by using butyric acid as a modulating agent. In the methyl orange (MO) adsorption experiments, H-MIL-101(Cr) showed a high adsorption capability of 369.8 mg g⁻¹, which was 1.52-fold greater than that of pristine MIL-101(Cr) (P-MIL-101(Cr)). While in the oxidation reaction of indene and 1-dodecene tests, H-MIL-101(Cr) presented much higher catalytic efficiency, with turnover frequency (TOF) values of 0.7242 mmol g⁻¹ min⁻¹ and 0.1492 mmol g⁻¹ min⁻¹, respectively, which were 28% and 34% greater than that in the case of P-MIL-101(Cr). Thus, compared with P-MIL-101(Cr), H-MIL-101(Cr) exhibited better removal efficiency and higher levels of activity in the oxidation reactions of indene and 1-dodecene. The unique structure of H-MIL-101(Cr) also contributed to its superior performance in these processes.     

PXR activation impairs hepatic glucose metabolism partly via inhibiting the HNF4α–GLUT2 pathway

Drug-induced hyperglycemia/diabetes is a global issue. Some drugs induce hyperglycemia by activating the pregnane X receptor (PXR), but the mechanism is unclear. Here, we report that PXR activation induces hyperglycemia by impairing hepatic glucose metabolism due to inhibition of the hepatocyte nuclear factor 4-alpha (HNF4α)‒glucose transporter 2 (GLUT2) pathway. The PXR agonists atorvastatin and rifampicin significantly downregulated GLUT2 and HNF4α expression, and impaired glucose uptake and utilization in HepG2 cells. Overexpression of PXR downregulated GLUT2 and HNF4α expression, while silencing PXR upregulated HNF4α and GLUT2 expression. Silencing HNF4α decreased GLUT2 expression, while overexpressing HNF4α increased GLUT2 expression and glucose uptake. Silencing PXR or overexpressing HNF4α reversed the atorvastatin-induced decrease in GLUT2 expression and glucose uptake. In human primary hepatocytes, atorvastatin downregulated GLUT2 and HNF4α mRNA expression, which could be attenuated by silencing PXR. Silencing HNF4α downregulated GLUT2 mRNA expression. These findings were reproduced with mouse primary hepatocytes. Hnf4α plasmid increased Slc2a2 promoter activity. Hnf4α silencing or pregnenolone-16α-carbonitrile (PCN) suppressed the Slc2a2 promoter activity by decreasing HNF4α recruitment to the Slc2a2 promoter. Liver-specific Hnf4α deletion and PCN impaired glucose tolerance and hepatic glucose uptake, and decreased the expression of hepatic HNF4α and GLUT2. In conclusion, PXR activation impaired hepatic glucose metabolism partly by inhibiting the HNF4α‒GLUT2 pathway. These results highlight the molecular mechanisms by which PXR activators induce hyperglycemia/diabetes.Key words: Pregnane X receptor, Hepatocyte nuclear factor 4-alpha, Glucose transporter 2, Hepatic glucose uptake, Diabetes, Drug-induced hyperglycemia     

软组织损伤超声治疗研究现状

尽管超声广泛用于治疗软组织损伤,而且超声的生物物理学效应通过体外研究也得以证实,但超声对软组织损伤的治疗效果仍受到质疑。很少有确切的证据表明超声治疗软组织损伤有效,其原因可能与多种因素有关,如技术方面的变数,临床研究中方法学的局限与缺陷,或者超声确实缺少治疗作用。     

Effect of Clopidogrel on Platelet Membrane CD40 Ligand in Coronary Artery Disease Patients Undertaking Percutaneous Coronary Intervention

Objectives To investigate the change and clinical significance of clopidogrel on platelet membrane CD40L in coronary artery disease patients before and after percutaneous coronary intervention(PCI). Methods 30 cases who were diagnosis coronary artery diseases(CAD) by coronary angiography, mean age 56±9 years old. All the patients who had no antiplatelet aggregation contraindication, were treated with standard anti angina pectoris drugs. Before PCI, all the patients took clopidogrel 75 mg per day. Activated platelet membrane CD40L express rate was measured by flow cytometry before and after PCI 6 hours. Results Activated platelet membrane CD40L express rate were 3.73±2.15 and 2.46±0.90, respectively in 30 patients before and after PCI 6 hours. Activated platelet membrane CD40L express rate was significantly decrease after PCI 6 hours than that before PCI(P<0.01). Conclusions Clopidogrel has significance effect on platelet membrane CD40L in coronary artery disease patients undergoing PCI. Clopidogrel can suppression platelet activation and prevent thromboembolism event occurrence.     

RP-HPLC法测定斑蝥素脂肪乳剂中斑蝥素的含量

目的　首次建立RP HPLC法测定斑蝥素脂肪乳剂中斑蝥素的含量。方法　采用C18柱 ,甲醇 水系统为流动相 ,梯度洗脱 ,紫外检测器 (检测波长为 2 2 7nm ,灵敏度为 0 0 0 5AUFS) ,对斑蝥素脂肪乳剂中斑蝥素进行含量测定。结果　样品处理简单 ,且能将斑蝥素与脂肪乳中的油脂、磷脂等主要杂质分离出来 ,斑蝥素在 2 0 8～ 31 2 μg·ml-1范围内峰面积与浓度线性关系良好 (r=0 994 ) ,最低可定量浓度为 1 0 4 μg·ml-1,样品回收率为 94 8%以上 ,进样精密度为 1 0 2 % (n =5 )。结论　该法测定脂肪乳样品分离效果好 ,回收率高 ,可作为斑蝥素脂肪乳剂质量控制方法。     

中药代谢分析研究进展＊

中药具有多成分、多靶点的特性，药效物质基础及药物代谢途径不明确严重制约中药的发展。中药小分子经过体内代谢后转化成代谢物发挥药效或者清除。近年来随着MS技术的飞速发展，通过LC-MS技术进行精准定性定量分析，以阐明中药代谢物与机体生理及病理相关变化的关系，从而明确中药的药效物质基础及体内代谢路径。本文从中药代谢研究思路、研究方法、影响因素以及应用等方面，就近年来中药代谢分析领域的研究进展进行综述。     

大鼠长期脾虚和热证造模的胃黏膜主细胞超微结构观察

目的模拟慢性病证是动物实验的主要难点。本实验观察比较大鼠长期(26周)脾虚和热证造模动物胃黏膜主细胞的超微结构。方法将Wistar大鼠随机分为对照组、脾虚组、热证组。对照组正常饲养26周;脾虚组用耗气破气加饥饱失常法造模26周;热证组灌喂熟附子、肉桂、干姜、女贞子煎剂26周。另取幼年大鼠为幼年组作为对照。实验结束后取胃体后壁组织,透射电镜观察胃黏膜主细胞超微结构。结果对照组主细胞粗面内质网排列基本整齐,部分内质网池略呈小泡状扩张。脾虚组主细胞粗面内质网池扩张,从小泡状至池状之间,甚至呈湖状。胞质内出现髓鞘样小体或髓鞘样结构。热证组主细胞粗面内质网池扩张,呈小泡状,失去正常的同心性层状结构。幼年组主细胞粗面内质网排列比较整齐。结论热证组和脾虚组动物胃黏膜主细胞超微结构均有变化,以脾虚组更为严重。由于实验时间较长,实验结束时大鼠已近1岁龄,所以对照组动物胃黏膜主细胞超微结构也略有衰老改变。     

以学生为案例望面色教学实践体会

望面色是望诊的主要内容之一,为了加强学生望面色这一诊断方法的学习效果,在征得学生同意,自愿参加的前提下,在学生中找典型面色进行真实案例教学,调动了学生学习积极性,取得了良好教学效果,实现了教学相长。