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.     

Synergism through combination of chemotherapy and oxidative stress-induced autophagy in A549 lung cancer cells using redox-responsive nanohybrids: A new strategy for cancer therapy

A combination of various therapeutic approaches has emerged as a promising strategy for cancer treatment. A safe and competent nano-delivery system is thus in urgent demand to facilitate the simultaneous transport of various therapeutic agents to cancer cells and a tumor region to achieve synergistic effect. Gold nanoparticles (GNPs) and mesoporous silica nanoparticle (MSNs) were fabricated herein as potential candidates for drug delivery. Serving as gatekeepers, GNPs (5 nm in diameter) were attached onto the amino-functionalized MSNs (denoted as NMSNs) via a relatively weak gold–nitrogen bonding. The resulting nanohybrids (denoted as GCMSNs) were uptaken by cells, and the detachment of GNPs and subsequent intracellular drug release from NMSNs were achieved by competitive binding of intracellular glutathione to GNPs. In addition to the function of gatekeeping, GNPs also play another role as the oxidative stress elicitor. Our in vitro studies revealed that GCMSNs induced higher oxidative stress in lung cancer cells (A549) than in normal cells (3T3-L1). This growth inhibitory effect found in the cancer cells was likely induced by mitochondria dysfunction originated from the GCMSN-induced, oxidative stress-triggered mitochondria-mediated autophagy. The redox-responsive nanohybrids were further loaded with camptothecin and the intensified synergistic therapeutic effects were observed associated with combined chemotherapy and oxidative stress strategy. The results clearly demonstrate that such unique nanohybrids hold great promise for selective and effective cancer treatments.     

Long-term skeletal stability in the treatment of mandibular prognathism with a physiological positioning strategy

Our aim was to evaluate the long-term skeletal stability of the mandible in 21 patients after orthognathic surgery with physiological positioning. The measurement points SNB, B point (X, Y), Pog (X, Y), and the angle of the ramus were measured on cephalometric photographs to assess skeletal stability preoperatively, immediately after operation, and one and two years postoperatively. In addition, we evaluated the clinical symptoms of disorders of the temporomandibular joint (TMJ). The analysis of the cephalometric photographs showed that SNB, B point X, and Pog X showed no significant differences among the postoperative time points. On the other hand, B point Y and Pog Y showed no significant differences throughout the study period. We compared the angle of the ramus before operation and two years postoperatively, and no significant difference was found. In addition, no cases showed any pathological symptoms of disorders of the TMJ two years postoperatively. The long-term stability after orthognathic surgery with physiological positioning was confirmed, and it seems to be a reliable orthognathic treatment in patients with mandibular prognathism.     

试论医学院校的转型和发展战略

我国医学院校的发展道路有通过“强强联合”并入综合性大学和通过学科多样化“转型”为多科性大学两种类型。“转型”方式虽然不受广泛的关注，却正在低调而广泛地运行，成为独立设置医学院校自我发展和提高的主要方式。转型期医学院校在发展战略上有明显共性，如专业学科布局的优化、大力扶植基础学科、整合临床资源凸显医学主体、校园规划和建设体现多科性大学的包容性等，应予以重视。     

Preparation of protected peptidyl thioester intermediates for native chemical ligation by Nα‐9‐fluorenylmethoxycarbonyl (Fmoc) chemistry: considerations of side‐chain and backbone anchoring strategies,and compatible protection for N‐terminal cysteine*,†

Abstract: Native chemical ligation has proven to be a powerful method for the synthesis of small proteins and the semisynthesis of larger ones. The essential synthetic intermediates, which are C‐terminal peptide thioesters, cannot survive the repetitive piperidine deprotection steps of N^α‐9‐fluorenylmethoxycarbonyl (Fmoc) chemistry. Therefore, peptide scientists who prefer to not use N^α‐t‐butyloxycarbonyl (Boc) chemistry need to adopt more esoteric strategies and tactics in order to integrate ligation approaches with Fmoc chemistry. In the present work, side‐chain and backbone anchoring strategies have been used to prepare the required suitably (partially) protected and/or activated peptide intermediates spanning the length of bovine pancreatic trypsin inhibitor (BPTI). Three separate strategies for managing the critical N‐terminal cysteine residue have been developed: (i) incorporation of N^α‐9‐fluorenylmethoxycarbonyl‐S‐(N‐methyl‐N‐phenylcarbamoyl)sulfenylcysteine [Fmoc‐Cys(Snm)‐OH], allowing creation of an otherwise fully protected resin‐bound intermediate with N‐terminal free Cys; (ii) incorporation of N^α‐9‐fluorenylmethoxycarbonyl‐S‐triphenylmethylcysteine [Fmoc‐Cys(Trt)‐OH], generating a stable Fmoc‐Cys(H)‐peptide upon acidolytic cleavage; and (iii) incorporation of N^α‐t‐butyloxycarbonyl‐S‐fluorenylmethylcysteine [Boc‐Cys(Fm)‐OH], generating a stable H‐Cys(Fm)‐peptide upon cleavage. In separate stages of these strategies, thioesters are established at the C‐termini by selective deprotection and coupling steps carried out while peptides remain bound to the supports. Pilot native chemical ligations were pursued directly on‐resin, as well as in solution after cleavage/purification.     

留置超滑乳胶气囊导尿管并发症的原因分析及对策

目的探讨留置超滑乳胶气囊导尿管并发症的原因及对策。方法对586例留置超滑乳胶气囊导尿管患者进行观察,回顾分析。结果留置超滑导尿管并发症与导尿方法、规范操作、留置导尿管的时间及相关知识宣教有关。结论严格无菌操作,选择合适的导尿管、缩短留置尿管的时间是降低并发症的重要措施。     

医学生"网络成瘾症"产生的原因和对策

文章针对目前医学生“网络成瘾症”的现状进行了分析,并指出了产生的原因和解决问题的办法,以求达到标本兼治。最后提出三点预防医学生“网络成瘾症”的对策：一是高校及其附属医院要为医学生营造宽松愉快的学习、生活环境;二是呼吁家长关注医学生身心发展的特殊规律,建立良好的家庭环境;三是建立和完善与网络社会相应的法律法规,规范医学生的网上行为。     

现代中医药发展战略思考

建国几十年来，由于党和政府的大力提倡和扶持，中医药得到了很大发展，但相对于西医的发展势头仍显不足。尤其是近10多年来，由于现代科技及现代管理学的有力推动，西医获得了突飞猛进的发展，然而，中医却由于种种原因发展相对缓慢。在这各行各业竞相发展的现代社会，中医要生存，就蓝须发展，中医要发展，就妊须总揽全局，从战略高度克服中医药发展的各种不利因素，充分发挥各方面的有利条件。     

单亲大学生心理健康状况及心理问题的教育对策研究

目的针对单亲大学生心理健康问题提供有效的教育对策．方法针对大学新生开展16PF调查并发现单亲大学生的心理问题。结果本次测查共测量被试8302人，删除部分无效量表．实际有效数据为7742人，问卷有效率为93．27％．以一般情况问卷中“是否是单亲家庭子女”回答“是”的．作为单亲大学生的认定标准，检出单亲家庭子女555人，占总人数的7．17%，其中男生占40．0％．女生60．0％．17．5％的单亲出现各种心理问题．调查表明．单亲家庭子女与非单亲家庭子女相比，在乐群性和怀疑性两个因子有显着区别。事实上也表现为与正常大学生心理健康状况的显着差异。结论单亲大学生心理问题表现为：自卑心理、怀旧心理、逆反心理、猜疑心理等等。教育对策：加强社会教育系统、学校教育系统、家庭教育对单亲大学生心理的干预与影响，同时．单亲大学生遗要加强心理健康的自我教育．以多元系统帮助他们形成健全人格。     

江门市区实施乙型肝炎免疫策略16年的效果评价

目的：对江门市区1986年1月1日起全面实施的乙型肝炎(乙肝)免疫策略进行效果评价。方法：运用血清流行病学调查和疫情资料对比分析，比较实施“免疫策略”前后江门市区0～15岁人群乙肝发病率和感染率变化情况和乙肝表面抗体(抗-HBs)增长情况。结果：实施“免疫策略”后16年，0～15人群的乙肝发病率由1985年的367．39／10万，降至2001年的21．10／10万，下降94．26％；HBsAg阳性率由1985年的9．17％降至2002年的0．6％，下降93．46％；乙肝病毒总感染率由1985年的35．82％降至2002年的1．20％，下降96．65％；抗-HBs阳性率由1985年的24．64％上升到2002年的93．00％，上升2．77倍。结论：江门市区现行乙肝免疫策略效果显，能有效预防和控制地区性大面积的乙肝流行与传播。经过一代人的努力，能彻底改变人口乙肝高发病率和HBV高感染率及高携带率的状况。