质子泵抑制剂用于肝硬化患者的疗效评估

目的观察质子泵抑制剂(PPI)对肝硬化患者临床症状、肝功能的影响。方法比较32例肝硬化患者PPI治疗前后肝功能、凝血功能、肝脏影像学、临床症状、并发症及不良反应等,分析PPI用于肝硬化的疗效。结果 PPI治疗后患者临床症状明显缓解,治疗前后症状对比为腹水为20例vs 4例(P=0.000),乏力为27例vs 10例(P=0.000),纳差为21例vs 6例(P=0.001)。门静脉内径较治疗前显著减小(后前对比):13.00 mm±1.08 mm vs 13.70 mm±1.38 mm(P=0.000)。PPI治疗后Child-Pugh评分较治疗前明显改善:Child A级为20例vs 10例,Child B级为10例vs 18例,Child C级为2例vs 4例(P=0.002)。PPI治疗1周前后ALT:44.30 u/L±22.72 u/L vs 36.02 u/L±22.63 u/L(P=0.001)。ALB较治疗前升高,TBIL下降,但差异均无统计学意义。观察期内,发生自发性腹膜炎者2例,并发肝肾综合征2例,其中1例死亡;发生肝性脑病者4例经治疗后均好转。结论 PPI用于肝硬化治疗,可减少肝功能损害、减轻门脉高压症及缓解临床症状;肝硬化患者应用PPI并不增加本病并发症的发生率,亦未见其他明显不良反应可能有益。     

RENAL EFFECTS OF CARDIAC ANGIOGRAPHY WITH DIFFERENT LOW-OSMOLAR CONTRAST MEDIA

The aim of this study was to evaluate the renal effects of cardiac angiography performed with three low-osmolar contrast media (CM): iopromide (IPR), ioversol (IVR) and ioxaglate (IOX). IPR and IVR are non-ionic CM, IOX is an ionic CM. Different parameters of renal function were determined before and 6, 24, 48, 72 hrs after angiography in 45 patients: 15 patients were examined with IPR, 15 with IVR and 15 with IOX. Glomerular effects – Plasma creatinine increased slightly at the 24th hour after IVR and IOX and at 48 hours after IOP. A significant increase in plasma β2-microglobulin was observed, at the same time, only after IOX. A significant decrease in creatinine clearance was found at 6 hours after IOX. No significant variations in glomerular filtration rate (GFR) and in effective renal plasma flow were found at 48 hours after cardiac angiography; while filtration fraction was significantly reduced after IOP and IOX. Tubular effects – A marked decrease in sodium clearance and a relevant increase of urinary activities of different tubular enzymes were found after cardiac angiography with all CM, but were more evident after the ionic CM IOX, than after the two non-ionic agents. These tubular effects reached the maximum between 6 and 24 hours and returned to baseline within 72 hrs after cardiac angiography. In conclusion, slight glomerular effects were observed mainly after IOX. A reversible tubular malfunction was found with the three low-osmolar CM and was more evident after ionic CM IOX, thus suggesting that other mechanisms, besides osmolarity, play a role in tubular toxicity due to CM. In no patient did the glomerular and tubular effects of CM have a clinical relevance.     

心血管病介入诊疗程序中第一术者有效剂量估算方法的比较研究

目的 通过模拟实验测量,比较国际辐射防护委员会（ICRP）139号报告推荐的4种单双剂量计算法对估算心血管介入诊疗程序中第一术者有效剂量之间的差异,以探讨这4种算法对介入诊疗场景的适用性。方法 模拟第一术者的男性躯干模体穿戴铅衣和铅围脖,在其体内布放热释光探测器,在其铅衣内外布放热释光个人剂量计,模拟心血管病介入诊疗场景,通过模拟测量得到的器官剂量计算第一术者的有效剂量,与通过个人剂量计及4种单双剂量计算法得到的结果进行比较。结果 在本实验条件下,由模拟测量计算得到的有效剂量为0.581 mSv;而用Swiss ordinance法、McEwan法、Von Boetticher法与Martin-Magee法估算得到的有效剂量分别为0.667、0.484、0.485和0.726 mSv,与模拟测量得到的有效剂量的相对偏差分别为14.8%、-16.7%、-16.5%和24.9%。结论 4种计算方法得到第一术者有效剂量与模拟测量结果均有较大的差异;从辐射防护观点出发,推荐使用Swiss ordinance法开展心血管病介入诊疗程序中第一术者的个人剂量监测。     

药用菊花中绿原酸合成途径关键酶基因的克隆及表达分析

目的探究淹水胁迫对杭菊绿原酸合成途径中的关键酶香豆酰基喹酸酯3’-单加氧酶(C3’H)和莽草酸羟基肉桂酰基转移酶(HCT)基因的表达和活性成分的影响。方法使用实时荧光定量PCR(qRT-PCR)方法基于杭菊转录组数据库克隆HCT和C3’H基因各2个,其中C3’H酶的2个基因CmC3’H1、CmC3’H2,HCT酶的2个基因CmHCT1、CmHCT2,并进行生物信息学分析;同时在杭菊花芽分化期进行淹水胁迫,以β-actin为内参基因,使用qRT-PCR检测以上4个基因的相对表达量;然后使用HPLC法测定杭菊这4个基因的下游产物及其他指标成分含量。结果通过研究获得了4条基因的完整开放阅读框,并且预测其氨基酸序列的相对分子质量和理论等电点(pI),同时构建蛋白质三级结构模型。qRT-PCR结果显示在花芽分化期对杭菊进行持续3 d的淹水处理会导致以上4个基因在不同生长时期内的表达显著变化。HPLC结果显示淹水处理后的杭菊C3’H和HCT所催化形成的下游产物绿原酸含量显著高于对照组,同时发现其他2种指标成分木犀草苷和3,5-O-二咖啡酰基奎宁酸含量也显著高于对照组。结论杭菊在淹水胁迫下可以通过调节4种基因的表达来调控下游产物的合成,从而对淹水胁迫做出应答,而且花芽分化期进行淹水胁迫可以显著增强杭菊活性成分的积累。     

基于多成分同时定量和统计学分析的大黄利胆片质量评价研究

目的建立用HPLC波长切换法同时测定大黄利胆片中10个活性成分没食子酸、5-羟甲基糠醛、柯里拉京、对羟基苯甲醛、鞣花酸、芦荟大黄素、大黄酸、大黄素、大黄酚、大黄素甲醚含量的方法,并结合统计学分析对其质量进行评价。方法采用PhenomenexKinetexC18色谱柱,柱温为30℃,以甲醇-0.15%磷酸水溶液为流动相梯度洗脱,体积流量为1m L/min,检测波长分别为265.0 nm(0～5.8 min,检测没食子酸)、283.9 nm(5.8～7 min,检测5-羟甲基糠醛)、222.2(7～18 min,检测柯里拉京、对羟基苯甲醛)、256.7 nm(18～74 min,检测鞣花酸、芦荟大黄素、大黄酸、大黄素、大黄酚、大黄素甲醚);用SPSS21软件对10批药中成分含量进行统计学分析。结果 10个成分在各自质量浓度范围内线性关系良好(r0.9980),平均加样回收率98.45%～100.12%,RSD为0.80%～2.51%;含量分别为没食子酸8.371～11.438mg/片、5-羟甲基糠醛0.046～0.087mg/片、柯里拉京0.721～2.094mg/片、对羟基苯甲醛0.034～0.065mg/片、鞣花酸1.736～1.996mg/片、芦荟大黄素0.337～0.440mg/片、大黄酸1.636～2.562mg/片、大黄素0.602～0.846mg/片、大黄酚0.388～0.566mg/片、大黄素甲醚0.621～0.781 mg/片;10批样品质量基本一致。结论该方法简单准确,可用于大黄利胆片的质量控制。     

Bottom-Up and Top-Down Approaches to Explore Sodium Dodecyl Sulfate and Soluplus on the Crystallization Inhibition and Dissolution of Felodipine Extrudates

The objectives of this study were to explore sodium dodecyl sulfate (SDS) and Soluplus on the crystallization inhibition and dissolution of felodipine (FLDP) extrudates by bottom-up and top-down approaches. FLDP extrudates with Soluplus and SDS were prepared by hot melt extrusion, and characterized by polarized light microscopy, differential scanning calorimetry, and fourier transform infrared spectroscopy. Results indicated that Soluplus inhibited FLDP crystallization, and the whole amorphous solid dispersions (ASDs) were binary FLDP-Soluplus (1:3) and ternary FLDP-Soluplus-SDS (1:2:0.15～0.3 and 1:3:0.2～0.4) extrudates. Internal SDS (5%-10%) decreased glass transition temperatures of FLDP-Soluplus-SDS ternary ASDs without presenting molecular interactions with FLDP or Soluplus. The enhanced dissolution rate of binary or ternary Soluplus-rich ASDs in the nonsink condition of 0.05% SDS was achieved. Bottom-up approach indicated that Soluplus was a much stronger crystal inhibitor to the supersaturated FLDP in solutions than SDS. Top-down approach demonstrated that SDS enhanced the dissolution of Soluplus-rich ASDs via wettability and complexation with Soluplus to accelerate the medium uptake and erosion kinetics of extrudates, but induced FLDP recrystallization and resulted in incomplete dissolution of FLDP-rich extrudates. In conclusion, top-down approach is a promising strategy to explore the mechanisms of ASDs' dissolution, and small amount of SDS enhances the dissolution rate of polymer-rich ASDs in the nonsink condition.     

Exploring the feasibility of the use of biopolymers as a carrier in the formulation of amorphous solid dispersions – Part I: Gelatin

Biopolymers have rarely been used so far as carriers in the formulation of amorphous solid dispersions (ASD) to overcome poor solubility of active pharmaceutical ingredients (APIs). In an attempt to enlarge our knowledge on this topic, gelatin, type 50PS was selected. A screening study was initiated in which twelve structurally different poorly soluble biopharmaceutical classification system (BCS) Class II drugs (carbamazepine, cinnarizine, diazepam, itraconazole, nifedipine, indomethacin, darunavir (ethanolate), ritonavir, fenofibrate, griseofulvin, ketoconazole and naproxen) were selected for evaluation. Solid dispersions of five different drug loadings of these twelve compounds were prepared by lyophilization and evaluated for their solid state properties by mDSC and XR(P)D, and in vitro dissolution performance. Even without any process optimization it was possible to form either fully amorphous or partially amorphous systems, depending on the API and API to carrier ratio. Hence in this respect, gelatin 50PS behaves as any other carrier. Dissolution of the API from the solid dispersions significantly exceeded that of their crystalline counterparts. This study shows the potential of gelatin as a carrier to formulate amorphous solid dispersions.     

湖北省原料药GMP认证中发现的主要缺陷及建议

目的：为全面理解原料药GMP认证相关标准,提高生产企业对原料药生产规范的认识和检查员的检查水平。方法：对2016年至2017年湖北省原料药现场检查中主要缺陷进行统计分析,对GMP认证中主要缺陷项目进行分类总结。结果与结论：通过共性问题,结合原料药产品的本身特点,建议加强各岗位操作人员培训,落实培训效果;合理设计厂房,加强硬件系统的改造;严格把关物料,做好溶剂回收工作;注重细节,有针对性做好确认与验证工作;文件管理系统化,记录填写规范化;引入风险管理,贯彻执行生产全过程管理;重视变更和偏差管理,提高质量意识;建立职业化检查员队伍。     

广州某地下人防工事空气氡浓度监测分析

目的 了解广州某地下人防工事空气氡浓度水平及其变化规律。方法 采用RAD7型测氡仪对指挥中心、通道等场所进行瞬时氡浓度测量与分析,并粗略估算氡及其子体所致工作人员年有效剂量。结果 指挥中心、无线通讯室、中央主通道和仓库区通道这4个有人员停留的主要工作场所的日间氡浓度均值分别为106.7、98.4、129.0、111.1 Bq/m³,总体平均为111.0 Bq/m³。²²²Rn子体所致工作人员的年有效剂量当量为0.400 mSv/a。结论 不同场所的氡浓度不尽相同,且其受通风、排水等人为活动的影响呈不同的变化规律。