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。     

Immunogenicity of next-generation HPV vaccines in non-human primates: Measles-vectored HPV vaccine versus Pichia pastoris recombinant protein vaccine

Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide. HPVs are oncogenic small double-stranded DNA viruses that are the primary causal agent of cervical cancer and other types of cancers, including in the anus, oropharynx, vagina, vulva, and penis. Prophylactic vaccination against HPV is an attractive strategy for preventing cervical cancer and some other types of cancers. However, there are few safe and effective vaccines against HPV infections. Current first-generation commercial HPV vaccines are expensive to produce and deliver.The goal of this study was to develop an alternate potent HPV recombinant L1-based vaccines by producing HPV virus-like particles into a vaccine that is currently used worldwide. Live attenuated measles virus (MV) vaccines have a well-established safety and efficacy record, and recombinant MV (rMV) produced by reverse genetics may be useful for generating candidate HPV vaccines to meet the needs of the developing world.We studied in non-human primate rMV-vectored HPV vaccine in parallel with a classical alum adjuvant recombinant HPV16L1 and 18L1 protein vaccine produced in Pichia pastoris. A combined prime-boost approach using both vaccines was evaluated, as well as immune interference due to pre-existing immunity against the MV.The humoral immune response induced by the MV, Pichia-expressed vaccine, and their combination as priming and boosting approaches was found to elicit HPV16L1 and 18L1 specific total IgG and neutralizing antibody titres. Pre-existing antibodies against measles did not prevent the immune response against HPV16L1 and 18L1.     

罗伊氏乳杆菌对轮状病毒感染肠炎患儿免疫功能与肠道菌群及临床疗效的影响

目的探究罗伊氏乳杆菌DSM 17938在治疗轮状病毒感染肠炎患儿中的疗效及对免疫功能、肠道菌群的影响。方法收集于2018年2月-2019年2月在阳光融和医院进行诊治的轮状病毒感染肠炎患儿126例,随机分为试验组(63例)和对照组(63例)。对照组给予常规补液治疗及蒙脱石散和枯草杆菌二联活菌口服治疗,试验组采用常规补液治疗及蒙脱石散和罗伊氏乳杆菌DSM 17938辅助治疗。观察两组患儿的腹泻改善情况,并分析对免疫功能(IgG、IgA、CD4^+/CD8^+水平)及肠道菌群失调的影响。结果在治疗72 h后,试验组患儿的治疗总有效率为92.06%,高于对照组的74.60%(P=0.009);且治疗后两组患儿的IgG、IgA、CD4^+/CD8^+水平均较治疗前有升高(P<0.05),且试验组水平高于对照组(P<0.05)。对患儿肠道菌群进行分析,在治疗1周后,试验组患儿肠道菌群失调程度低于对照组,且试验组的肠道菌群正常比例高于对照组(P<0.05)。结论罗伊氏乳杆菌DSM 17938对于辅助治疗轮状病毒感染肠炎患儿具有良好的疗效,能够提高患儿免疫力,改善肠道菌群失调,减轻患儿腹泻症状,具有一定的临床应用价值。     

“互联网+”时代下中药药剂学的教学思索

作为信息时代一种全新的经济形态,“互联网+”是依托互联网信息技术将互联网技术与传统资源进行重新整合,以优化资源的有效配置、升级业务体系、重新构建商业模式等途径来完成经济转型和更新。“互联网+”时代的到来,深刻影响着各行各业包括教育领域,通过教学新手段的引入,改变了中药药剂学传统的教学方式,更加有利于提高课堂效率,有助于培养新型医药人才,适应社会的发展。     

Ad-CD40L mobilizes CD4 T cells for the treatment of brainstem tumors

BackgroundDiffuse midline glioma, formerly DIPG (diffuse intrinsic pontine glioma), is the deadliest pediatric brainstem tumor with median survival of less than one year. Here, we investigated (i) whether direct delivery of adenovirus-expressing cluster of differentiation (CD)40 ligand (Ad-CD40L) to brainstem tumors would induce immune-mediated tumor clearance and (ii) if so, whether therapy would be associated with a manageable toxicity due to immune-mediated inflammation in the brainstem.MethodsSyngeneic gliomas in the brainstems of immunocompetent mice were treated with Ad-CD40L and survival, toxicity, and immune profiles determined. A clinically translatable vector, whose replication would be tightly restricted to tumor cells, rAd-Δ24-CD40L, was tested in human patient–derived diffuse midline gliomas and immunocompetent models.ResultsExpression of Ad-CD40L restricted to brainstem gliomas by pre-infection induced complete rejection, associated with immune cell infiltration, of which CD4+ T cells were critical for therapy. Direct intratumoral injection of Ad-CD40L into established brainstem tumors improved survival and induced some complete cures but with some acute toxicity. RNA-sequencing analysis showed that Ad-CD40L therapy induced neuroinflammatory immune responses associated with interleukin (IL)-6, IL-1β, and tumor necrosis factor α. Therefore, to generate a vector whose replication, and transgene expression, would be tightly restricted to tumor cells, we constructed rAd-Δ24-CD40L, the backbone of which has already entered clinical trials for diffuse midline gliomas. Direct intratumoral injection of rAd-Δ24-CD40L, with systemic blockade of IL-6 and IL-1β, generated significant numbers of cures with readily manageable toxicity.ConclusionsVirus-mediated delivery of CD40L has the potential to be effective in treating diffuse midline gliomas without obligatory neuroinflammation-associated toxicity.     

马齿苋“成分-活性-中药功效-疾病”研究进展及关联分析

马齿苋是一种药食同源品,具有清热解毒、凉血止血、止痢的功效,为常见中药,作为药物安全性高。马齿苋具有多种活性成分及药理作用,为了充分开发利用马齿苋,加快马齿苋研究的现代化进程,综述马齿苋的研究进展并在此基础上对于其"成分-活性-中药功效-疾病"进行关联分析,为马齿苋的现代化研究提供思路。