中药生产过程质量控制关键技术研究进展

中医药发展已上升到国家战略层面,在医药行业贯彻实施"中国制造2025"战略的新形势下,中药生产过程质量控制是中药工业需要加快突破的关键领域之一。对中药生产过程质量控制领域在工艺设计、分析检测、过程建模、制造装备等方面的关键共性问题进行解析,综述了中药生产过程质量控制体系中工艺过程理解、生产过程实时分析方法开发、过程控制策略建立3个方面的研究进展;并结合企业研究实践,介绍了质量源于设计(quality by design,Qb D)、过程分析技术(process analytical technology,PAT)、实验设计(design of experiment,DOE)、多变量统计分析等关键技术在上述3个研究方向中的应用进展,分析了实际工业应用的难点问题并对其应用前景进行展望,旨在为中药企业应用和提升生产过程质量控制技术提供参考。     

Anxiety sensitivity as a mediator of the association between asthma and smoking

Objective: Despite its negative effects, smoking is more common among individuals with asthma compared to those without. Anxiety sensitivity (fear of arousal-related sensations) is associated with both smoking and asthma; however, no research, to date, has examined the interplay between these three factors. Thus, the purpose of the current study was to evaluate the mediating role of anxiety sensitivity in the association between asthma diagnosis and smoking status. Methods: The current study was a secondary analysis of data from three existing datasets of non-smokers and smokers with and without asthma (n?=?433; 56.3% female, M_age?=?34.01 years, SD?=?13.9). Participants provided information on their asthma diagnosis status and smoking status and completed self-report measures. Results: As hypothesized, after controlling for gender, race and age, there was a significant indirect effect of asthma diagnosis on smoking status through anxiety sensitivity (95% CI?=?0.07–0.48). Conclusions: These results indicate that the association between asthma diagnosis and smoking status appears to be driven, in part, by anxiety sensitivity and suggest that anxiety sensitivity may serve as an important target for prevention and intervention efforts for smokers with asthma.     

儿童精神分裂症患者的预后及相关因素分析

目的探讨儿童精神分裂症的预后及其影响因素。方法收集1987—1997年首次住院的儿童(起病年龄≤14岁)精神分裂症患者(儿童组)124例和同期首次住院的成人(起病年龄25～30岁)精神分裂症患者(成人组)120例,采用社会功能缺陷量表(SDSS)、日常生活能力量表(ADL)、大体评定量表(GAS)及自制调查表,以随访与量表现场测评相结合的方法获得资料,数据采用多因素回归分析。结果(1)儿童组服药依从性(90例,77.6%)好于成人组(73例,64.0%；)χ~2= 5.11,P＜0.05)；复发率(29.3%)低于成人组(42.1%；χ~2=4.10,P＜0.05)。(2)儿童组预后良好者(91例,78.4%)显著多于成人组(65例,57.0%)。(3)儿童组的社会功能[(2.11±1.02)分]和日常生活能力[(18.78±9.17)分]优于成人组[(3.48±1.86)分和(21.82±8.67)分；P＜0.01和P＜0.05]。(4)经多因素回归分析,影响儿童精神分裂症预后的主要因素有：社会家庭关爱程度,首次住院疗效,起病形式,服药时间和病期(P＜0.01)。结论儿童精神分裂症患者总体预后较好；充分的家庭关爱,首次住院疗效好,急性起病,坚持长期治疗和病期较短者的预后更好。     

结核分枝杆菌稳定L型变异的聚合酶链反应研究

目的：探讨结核分枝杆菌稳定L型变异的分子机制。方法：采用结核分枝杆菌聚合酶链反应(PCR)诊断试剂扩增结核分枝杆菌稳定L型纯培养物的染色体DNA，琼脂糖凝胶电泳、聚丙烯酰胺凝胶电泳(polyscrylamid gel electrophoresis，PAGE)薄层凝胶扫描分析。结果：结核分枝杆菌稳定L型比细菌型多一DNA条带。结论：结核分枝杆菌稳定L型的形成可能与基因突变有关，在特异性PCR反应中可形成与其亲代细菌型有差异的产物。     

How many subjects are needed in a longitudinal birth cohort study?

One of the first decisions that needs to be taken when planning a birth cohort concerns the size of the study. This in turn will depend on the research questions to be answered and thence whether environmental exposures and outcomes are measured on a continuum or as dichotomous variables. Here we describe ways in which different birth cohorts have addressed this issue and explore the advantages of smaller detailed studies over larger less-detailed studies.     

In vitro/in vivo correlation of prolonged release dosage forms containing diltiazem HCl

Six preparations were considered: three multiple unit dosage forms (micropellets in capsules) (D, E and G) and one matrix tablet (B) were experimental prolonged release formulations, two non-disintegrating tablets (A and C) were commercial products. The in vitro dissolution behaviour of the differing formulations was investigated using the USP XXII paddle apparatus. The in vivo study was effected on a panel of 12 healthy volunteers. The two commercial tablets (A and C) showed mean dissolution time (MDT) of 1.34 and 1.44 h and t_d of 91 and 92 min, respectively; for prolonged release formulations (B, E, D, and G) MDT ranged between 2.28 and 4.23 h and t_d between 149 and 291 min. The mean residence time (MRT) was 8.68 and 6.47 h for tablets A and C, respectively; it ranged between 9.62 and 10.24 h for the multiple unit formulations E, D, and G and was 11.27 h for matrix B. Formulation B also showed the higher apparent elimination half-life t_1/2 (7.12 h), while apparent t_1/2 for all the other formulations were very similar, ranging between 5.04 and 5.28 h. High variability between the various formulations was found for C_max and AUC values, and no relationships could be established with the type of formulation. An in vitro/in vivo correlation was found for all the formulations examined on the basis of analogous parameters (MDT and MRT); (r = 0.83, p <0.05). In a few cases the Wagner-Nelson deconvolution method was applied to individual plasma level versus time curves and the corresponding absorption curves were obtained. In these cases the in vitro/in vivo correlation was tested on the basis of the comparison of the in vivo absorption curves with the in vitro dissolution profiles. This was accomplished using the ‘Levy's plot’ (per cent released versus per cent absorbed) approach and provided further support for the correlation found.     

A preliminary statistical model for identifying repeaters of parasuicide

This paper presents a statistical model constructed using logisticregression to identify those at high-risk of repeating parasuicide. Thesubjects in the study are Cork city residents who exhibited parasuicidalbehaviour between 1 January and 30 June 1995. Repetition of the behaviourwithin six months of the index episode distinguishes repeaters fromnon-repeaters. The model was designed so that it could be used bynon-clinicians and hence does not require information relating topsychiatric diagnosis or use of psychiatric services. The proportion ofsubjects correctly classified remained stable across a range of cut-pointprobabilities (mean = 86%, range: 83.9–87.5%). Using acut-point of 0.2, 96% of repeaters and 81% of non-repeaters were correctly classified. Using 0.45 led to the correct identification of81% of repeaters and 90% of non-repeaters. If these highlevels of sensitivity and specificity are maintained in validation tests onfuture cohorts in Cork city then the model could form the basis of anintervention programme designed to prevent the repetition of parasuicide.