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。     

Direct insertion of an ultra‐slim upper endoscope for cholangioscopy in patients undergoing choledochoduodenostomy

Direct peroral cholangioscopy (POC) using an ultra‐slim upper endoscope is one modality of POC for intraductal endoscopic evaluation and treatment of the bile duct. Choledochoduodenostomy (CDS) is one modality of biliary bypass surgery that provides a new route to the bile duct. We carried out direct POC using an ultra‐slim upper endoscope without the use of accessories in 10 patients (four sump syndromes, three bile duct strictures and three intrahepatic duct stones) previously undergoing surgical CDS. Direct POC was successful in all patients. The use of an intraductal balloon catheter was required in one patient for advancement of the endoscope into the bile duct. Distal bile ducts with sump syndromes were cleared using baskets and water irrigation under direct POC. Cholangiocarcinoma was diagnosed in one patient with hilar bile duct stricture after cholangioscopic evaluation and a targeting forceps biopsy under direct POC. Intrahepatic duct stones were successfully extracted after intraductal fragmentation under direct POC. Oozing bleeding occurred during intraductal lithotripsy but stopped spontaneously. Direct POC using an ultra‐slim upper endoscope without the assistance of accessories can easily be carried out in patients undergoing CDS.     

深圳市制造企业90后新招产线员工心理弹性、应对方式与心理健康间的关系

目的探讨深圳市3家制造企业新招90后产线员工心理弹性、应对方式和心理健康间是否存在某种关系。方法在深圳市3家制造企业选取入职一周的新招90后产线员工,以其入职日期为单位进行整群抽样。应用心理弹性量表CDRISC、简易应对方式问卷SCSQ以及一般健康问卷GHQ-20三个量表分别测量其心理弹性、应对方式以及心理健康,并利用结构方程模型软件Amos 17.0进行路径分析。结果心理弹性与心理健康呈正相关关系(P<0.01);心理弹性和心理健康与积极应对呈正相关关系(P<0.01);心理弹性和心理健康与消极应对呈负相关关系(P<0.01);结构方程模型结果表明:心理弹性既可以直接影响心理健康,又可以通过积极应对和消极应对的中介作用间接影响心理健康。结论深圳市制造企业新招产线员工的心理弹性、应对方式与心理健康间存在线性相关关系,且心理弹性通过积极应对和消极应对对心理健康起着部分间接的作用。     

苯扎贝特治疗儿童ApoE Tokyo(Arg25Cys)突变型脂蛋白肾病1例

脂蛋白肾病(Lipoprotein glomerulopathy,LPG),1989年首次由日本学者Saito报道,LPG主要累及肾脏,且以肾小球病变为主[1]。几乎所有患者均有不同程度的蛋白尿,多数表现为肾病综合征,少数表现为轻微蛋白尿和镜下血尿,部分患者伴有不同程度的贫血及高血压,血脂异常易被忽略为肾病综合征的低蛋白血症所致。载脂蛋白E(apolipoprotein E,ApoE)增高是LPG血脂改变的主要特点[2-3]。LPG为一种与脂质代谢紊乱密切相关的肾脏疾病,目前世界范围内有报道的病例不足200例,儿童报道仅10余例[2]。本病进展缓慢,临床常误诊为原发性肾病综合征[4]。因此,为增强对LPG的认识,提高诊治水平,现分析1例确诊的儿童LPG临床资料,总结LPG的临床特点、诊断、治疗及预后。     

Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response

BACKGROUND. The identification and treatment of individuals with tuberculosis (TB) is a global public health priority. Accurate diagnosis of pulmonary active TB (ATB) disease remains challenging and relies on extensive medical evaluation and detection of Mycobacterium tuberculosis (Mtb) in the patient’s sputum. Further, the response to treatment is monitored by sputum culture conversion, which takes several weeks for results. Here, we sought to identify blood-based host biomarkers associated with ATB and hypothesized that immune activation markers on Mtb-specific CD4⁺ T cells would be associated with Mtb load in vivo and could thus provide a gauge of Mtb infection.METHODS. Using polychromatic flow cytometry, we evaluated the expression of immune activation markers on Mtb-specific CD4⁺ T cells from individuals with asymptomatic latent Mtb infection (LTBI) and ATB as well as from ATB patients undergoing anti-TB treatment.RESULTS. Frequencies of Mtb-specific IFN-γ⁺CD4⁺ T cells that expressed immune activation markers CD38 and HLA-DR as well as intracellular proliferation marker Ki-67 were substantially higher in subjects with ATB compared with those with LTBI. These markers accurately classified ATB and LTBI status, with cutoff values of 18%, 60%, and 5% for CD38⁺IFN-γ⁺, HLA-DR⁺IFN-γ⁺, and Ki-67⁺IFN-γ⁺, respectively, with 100% specificity and greater than 96% sensitivity. These markers also distinguished individuals with untreated ATB from those who had successfully completed anti-TB treatment and correlated with decreasing mycobacterial loads during treatment.CONCLUSION. We have identified host blood-based biomarkers on Mtb-specific CD4⁺ T cells that discriminate between ATB and LTBI and provide a set of tools for monitoring treatment response and cure.TRIAL REGISTRATION. Registration is not required for observational studies.FUNDING. This study was funded by Emory University, the NIH, and the Yerkes National Primate Center.     

七氟烷和丙泊酚对心脏双瓣置换术麻醉期间血流动力学变化的影响

目的探讨七氟烷、丙泊酚对心脏双瓣置换术麻醉期间血流动力学变化的影响。方法选取2010年5月至2012年5月在东莞康华医院进行风湿性心脏双瓣膜置换术治疗的患者60例作为研究对象。根据不同的麻醉用药将患者分成七氟烷组和丙泊酚组。七氟烷组患者采用1%七氟烷进行麻醉诱导;丙泊酚组患者采用丙泊酚进行麻醉诱导。分别在术前、主动脉开放后第2、8、24小时测定血流动力学变化;在术前及主动脉开放后第8、16、72小时监测血清总胆红素(TBIL)、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)等指标。结果两组心脏双瓣置换术患者的平均动脉压(MAP)、心率(HR)、肺动脉楔嵌压(PAWP)、总胆红素、AST、ALT组间差异无统计学意义(P>0.05),不同时点间及组间·不同时点间比较差异有统计学意义(P<0.05);氘代试剂(CIL)、每搏输出量指数(SVI)、左心室做功指数(LVSW)、血尿素氮(BUN)、肌酐(Cr)组间、不同时点间、组间·不同时点间比较,差异有统计学意义(P<0.05)。结论对心脏双瓣膜置换术患者实施七氟烷或靶控输注丙泊酚进行麻醉诱导,对患者MAP、HR、PAWP、TBIL、AST及ALT的影响相似,但是对SVI、LVSWI、BUN及Cr的影响有一定的差异,可根据患者的具体情况选择适当的麻醉方法。     

谷氨酸对腺苷A2A受体调节一氧化氮合酶活力的影响

目的探讨谷氨酸是否能够影响腺苷A2A受体对一氧化氮合酶（NOS）活力的调节。方法用1000ng／ml脂多糖（LPS）刺激小胶质细胞，分别加入100nmol／L A2A受体激动剂CGS21680以及不同浓度的谷氨酸（0，1，0，25，0，5mmol／L）干预，观察NOS活力变化。结果LPS诱导NOS活力增高，激活A2A受体可以产生抑制作用；0，25及0．5mmoL／L谷氨酸和A2A受体激动剂同时存在时，NOS活力进一步增高。结论高浓度谷氨酸可逆转腺苷A2A受体激动剂抑制升高NOS活力的作用。     

肝癌间质及癌旁病变的病理分析

目的　研究肝癌间质及癌旁病变的临床病理意义。方法　在 2 0例肝癌组织标本中取 45个癌结节 ,分别在癌结节中间、癌旁肝组织等部位取组织 4块 ,连续切片 ,显微镜下观察。结果　 19个结节有完整窦内皮细胞围绕癌巢 ,其中癌结节肉眼小于3cm者 13个 ,大于 3cm者 6个。 2 6个癌结节无完整窦内皮细胞围绕癌巢 ,其中癌结节直径大于 3cm者 2 4个 ,小于 3cm者 2个。2 0例中有 13例合并肝硬化 ,17例有乙型肝炎病毒感染和HBsAg阳性。 结论　病理连续切片 ,显微镜下观察肝癌间质及癌旁病变是预测肝癌患者预后的重要病理学指标