A Proposal for an Alternative Approach to Particle Size Method Development During Early-Stage Small Molecule Pharmaceutical Development

Particle size analysis in the pharmaceutical industry has long been a source of debate regarding how best to define measurement accuracy; the degree to which the result of a measurement or calculation conforms to the true value. Defining a “true” value for the size of a particle can be challenging as the output of its measurement will differ because of variations in measurement approaches, instrumental differences and calculation methods. Consequently, for “real” particles, a universal “true” value does not exist and accuracy is therefore not a definable characteristic. Accordingly, precision is then a measure of the ability to reproducibly achieve a measurement of unknown relevance.This article proposes, in place of accuracy, a means to define the “appropriateness” of a measurement in line with the critical quality attributes (CQA) of the material being characterized. The decision as to whether the measurement is correct should involve a link to the CQA; that is, correlation should be demonstrated, without which the measured particle size cannot be defined as a critical material attribute.Correspondingly, methods should also be able to provide sufficient precision to demonstrate discrimination relating to variation in the CQA. The benefits and challenges of this approach are discussed.     

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。     

神经源性声带运动障碍与喉神经电生理

声带运动障碍的病因和临床表现复杂多变，涉及多学科，从病因上分为神经源性和非神经源性。对于神经源性声带运动障碍的诊治，首先通过喉镜等检查明确有无声带运动障碍及严重程度，值得注意的是声带纵向张力变化障碍也属于运动障碍的范畴；然后采用喉肌电图（LEMG）检查进行定性分析，在确诊神经源性损伤后，进一步对神经损伤部位进行定位诊断并查找导致神经损伤的病因；同时根据喉部神经电生理评估结果，判断预后。最后综合上述的评估结果制定相应的治疗策略。     

The proteome microenvironment determines the protective effect of preconditioning in cisplatin-induced acute kidney injury

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Outcomes after neoadjuvant or adjuvant chemotherapy for cT2-4N0-1 non–small cell lung cancer: A propensity-matched analysis

Objective

Comparative survival between neoadjuvant chemotherapy and adjuvant chemotherapy for patients with cT2-4N0-1M0 non–small cell lung cancer has not been extensively studied.

肿瘤坏死因子-α-308基因对导管相关性脓毒症患者病情的影响

目的探究肿瘤坏死因子-α(Tumornecrosis factor-α,TNF-α)-308基因对导管相关性脓毒症(Catheter related sepsis,CRS)患者病情的影响,旨在为临床治疗CRS提供科学依据。方法选取2017年7月-2018年10月于浙江大学医学院附属杭州市第一人民医院接受治疗的86例CRS患者为研究对象,按照是否并发多器官功能障碍综合征将患者分为试验组和对照组,对照组共48例,未并发多器官功能障碍综合征,试验组共38例,并发多器官功能障碍综合征,分析两组患者TNF-α-308基因多态性差异,使用多因素Logistic回归分析CRS患者并发多器官功能障碍综合征的危险因素。结果试验组GA基因型频率34.21%、AA基因型频率50.00%、高G等位基因频率18.42%均高于对照组,GG基因型频率52.63%、A等位基因频率28.95%均低于对照组,差异均具有统计学意义(P<0.05);多因素Logistic回归分析结果显示,低GG基因型频率、低G等位基因频率、高GA基因型频率、高AA基因型频率、高A等位基因频率是CRS患者并发多器官功能障碍综合征的危险因素(P<0.05)。结论TNF-α-308基因与CRS患者病情密切相关,GG基因型频率和G等位基因频率降低,GA基因型频率、AA基因型频率、A等位基因频率升高会加重患者的病情,增加多器官功能障碍综合征的发生风险,临床上应该加以重视。     

奥扎格雷联合低分子肝素钙治疗脑血栓的临床研究

目的：对应用低分子肝素钙与奥扎格雷联合对患有脑血栓疾病的患者实施治疗的临床效果进行研究。方法整群选择在该院2012年12月—2014年12月就诊的患有脑血栓疾病的患者86例，随机分为对照组和治疗组，每组43例。采用奥扎格雷对对照组患者实施治疗；采用低分子肝素钙与奥扎格雷联合对治疗组患者实施治疗。对比神经功能缺损评分在药物治疗前后的变化幅度、脑神经功能恢复正常时间和脑血栓药物治疗计划实施总时间、脑血栓疾病药物治疗效果、用药期间的不良反应人数。结果治疗组患者神经功能缺损评分在药物治疗前后的变化幅度明显大于对照组；脑神经功能恢复正常时间（9.66±2.41）d和脑血栓药物治疗计划实施总时间（13.28±2.14）d明显短于对照组（13.62±3.47）、（17.39±3.20）d；脑血栓疾病药物治疗效果（总有效率90.6%）明显优于对照组（总有效率69.8%）；用药期间的不良反应人数（1例）明显少于对照组（8例）。结论应用低分子肝素钙与奥扎格雷联合对患有脑血栓疾病的患者实施治疗的临床效果非常明显。     

Atypical Abnormal Pulmonary Vein Drainage with Atrial Septal Defect: Surgical Treatment

Sinus venosus atrial septal defect (SV‐ASD) usually coexists with partial anomalous pulmonary vein connection (PAPVC). It is a difficult diagnosis in transthoracic echocardiography (TTE) due to eccentric position of defects. We present a rare case of atypical anatomical variation in PAPVC, which was never described before. Two right pulmonary veins drained into superior vena cava, which overrode SV‐ASD and interatrial septum, a third pulmonary vein into the right atrium. Complete diagnosis could not be set after TTE, nor transesophageal echocardiography, whereas angio‐CT was finally conclusive. This diagnostic approach allowed the surgical planning.