国产水痘减毒活疫苗质量分析

目的 对国产水痘减毒活疫苗进行质量分析，判断疫苗的安全性和有效性。方法 取2019年生产的102批水痘减毒活疫苗，进行鉴别试验、外观、pH值、渗透压摩尔浓度、水分、病毒滴定、热稳定性、牛血清白蛋白残留量、抗生素残留量、无菌、异常毒性、细菌内毒素含量的检查。结果 各项检查结果均符合《水痘减毒活疫苗制造与检定规程》和中国药典2015年版三部相关要求，病毒滴定和热稳定性试验结果均在3.4 lg噬斑形成单位/0.5 ml以上。结论  国产水痘减毒活疫苗是安全有效的。     

新常态下基层医疗机构党支部组织生活创新研究

党的组织生活是党的生活的重要内容,还是增强党支部各项组织生活所具有的活力、增强基层党组织自身的凝聚力、吸引力等最为高效的一种方法。该研究以齐贤社区卫生服务中心全体职工为研究对象,从党内外职工两个角度,发现党支部组织生活存在问题,以问题为导向,创建出一支生机勃勃、能力与党性兼备的基层医疗机构。充分发挥新常态下基层党支部的先锋模范及战斗堡垒作用。     

Cordycepin protects PC12 cells against 6-hydroxydopamine induced neurotoxicity via its antioxidant properties

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is characterized by degeneration and loss of dopaminergic neurons of the substantia nigra. Increasing evidence has indicated that oxidative stress plays a pivotal role in the pathogenesis of Parkinson’s disease (PD). Therapeutic options that target the antioxidant machinery may have potential in the treatment of PD. Cordycepin, a nucleoside isolated from Cordyceps species displayed potent antioxidant, anti-inflammatory and anticancer properties. However, its neuroprotective effect against 6-OHDA neurotoxicity as well as underlying mechanisms is still unclear. In this present study, we investigated the protective effect of cordycepin against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity and its underlying mechanism. We observed that cordycepin effectively inhibited 6-OHDA-induced cell death, apoptosis and mitochondrial dysfunction. Cordycepin also inhibited cell apoptosis induced by 6-OHDA as observed in the reduction of cytochrome c release from the mitochondrial as well as the inhibition of caspase-3. In addition cordycepin markedly reduced cellular malondialdehyde (MDA) content and intracellular reactive oxygen species (ROS) level. Cordycepin also significantly increased the antioxidant enzymes; superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in 6-OHDA-treated cells. The results obtained unambiguously demonstrated that cordycepin protects PC12 cells against 6-OHDA-induced neurotoxicity through its potent antioxidant activity.     

Sabin株脊髓灰质炎病毒灭活疫苗的制备及免疫原性评价

目的  建立Sabin株毒种制备脊髓灰质炎灭活疫苗（inactivated poliovirus vaccine, IPV）生产工艺并评价其免疫原性。方法  采用Vero细胞培养Sabin株脊髓灰质炎Ⅰ、Ⅱ、Ⅲ型病毒,制备3价Sabin株IPV（Sabin strain IPV, sIPV）。通过ELISA检测D抗原含量。检测病毒滴度,电子显微镜下观察纯化病毒形态并电泳鉴定,分析抗原纯度,同时检测纯化原液宿主细胞残余DNA和蛋白含量。通过大鼠体内接种法比较sIPV和野生株IPV免疫原性,并观察中和抗体滴度变化。结果 Ⅰ、Ⅱ、Ⅲ型收获液D抗原含量分别为2 437、365、1 253 DU/ml,病毒滴度分别为每毫升8.4 、7.8和7.9 lg半数细胞培养物感染量。纯化病毒抗原纯度均﹥99%。电子显微镜下观察可见直径20~30 nm病毒颗粒,电泳鉴定正确。纯化原液的残余宿主细胞DNA和蛋白含量分别12.3 pg/500 μl和9.8 ng/ml。sIPV 3针免疫后在大鼠体内诱导产生抗Ⅰ、Ⅱ、Ⅲ型中和抗体的几何平均滴度分别为9 397.8、554.7和4 668.4,与野生株IPV相比Ⅰ型明显增高（t=-3.429,P=0.004）,Ⅱ、Ⅲ型无明显差别,初免后19周内均维持在较高水平。结论 建立了稳定的sIPV生产工艺,制备的sIPV免疫原性较好。     

卡介菌多糖核酸治疗口腔扁平苔藓有效性和安全性的荟萃分析

目的   荟萃分析卡介菌多糖核酸治疗口腔扁平苔藓的有效性和安全性。方法   检索美国医学文献数据库、Embase、Cochrane图书馆、万方数据库、维普数据库、中国期刊全文数据库、中国生物医学文献数据库、中国临床试验注册中心、美国临床试验注册中心,搜集卡介菌多糖核酸与非卡介菌多糖核酸比较治疗口腔扁平苔藓的临床随机对照试验。筛选文献和提取有效数据后,根据Jadad质量评分法对纳入荟萃分析的文献进行评分。采用STATA 15.0统计软件进行荟萃分析、敏感性分析和发表偏倚分析。结果   6篇文献符合纳入标准,共计484例患者。荟萃分析结果显示卡介菌多糖核酸治疗组（试验组）总有效性优于非卡介菌多糖核酸治疗组（对照组）（优势比＝2.29,95％置信区间：1.57~3.35,P<0.05）,复发率低于对照组（相对危险度＝0.50,95％置信区间：0.32~0.79,P<0.05）,差异具有统计学意义。两组均无严重不良反应发生,且发生不良反应例数无统计学差异（相对危险度＝0.57,95％置信区间：0.19~1.71,P＞0.05）。Begg’s 检验结果显示未存在明显发表偏倚。结论  卡介菌多糖核酸治疗口腔扁平苔藓的临床效果优于对照组,且尚无严重不良反应发生,临床上值得推广应用。     

Designing an immunocyte-targeting delivery system by use of beta-glucan

A β-1,3-d-glucan called Schizophyllan (SPG) can form a novel complex with homo oligodeoxynucleotides (ODNs) via the combination of hydrogen bonding and hydrophobic interactions. Dectin-1 is a major receptor involved in the recognition of β-1,3-d-glucans and expressed on antigen presenting cells (APCs) including macrophages, dendritic cells, monocytes, neutrophils, and a subset of T cells. Therefore, the SPG/ODN complex can be used as APCs cell-specific delivery of functional ODNs including unmethylated CpG sequences (CpG-ODNs). In fact, CpG-ODN/SPG complex induced high antibody titers when it was administered to cynomolgus monkeys as adjutant of influenza vaccine. These results indicate that SPG can be an excellent immunocyte-targeting drug delivery system.     

Dietary exposure to mycotoxins and health risk assessment in the second French total diet study

Mycotoxins are produced in plants by micro-fungi species, and naturally contaminated the food chain. In the second French total diet study (TDS), mycotoxins were analyzed in 577 food samples collected in mainland France to be representative of the population diet and prepared 〈〈as consumed〉〉. Highest mean concentrations were found in wheat and cereal-based products (bread, breakfast cereals, pasta, pastries, pizzas and savoury pastries…). Exposure of adult and child populations was assessed by combining national consumption data with analytical results, using lowerbound (LB) and upperbound (UB) assumptions for left-censorship management. Individual exposures were compared with available health-based guidance values (HBGV). Only the exposure to deoxynivalenol (DON) and its acetylated derivatives was found to significantly exceed the HBGV in LB in adults (0.5% [0.1; 0.8]) and children (5% [4; 6]). HBGV was exceeded in UB only for T-2 and HT-2 toxins by, respectively, 0.2% [0.02; 0.05] and 4% [3; 5] of adults, and 11% [9; 12] and 35% [32; 37] of children. Although the exposures assessed were generally lower than the previous French TDS, the results indicated a health concern for trichothecenes and a need to reduce dietary exposure as well as analytical limits.     

皮内注射用卡介苗生产场地变更质量可比性研究

目的  对发生场地变更的皮内注射用卡介苗产品进行关键质量要素对比和分析,确认变更后产品质量与变更前一致。方法  对新老车间卡介苗产品关键质量指标进行分析,同时对卡介苗成品稳定性、卡介菌结构特异性、卡介苗成品动物安全性等方面进行比较研究。结果  新老车间卡介苗产品的关键质量指标均符合相关规定要求,其中新车间卡介苗半成品沉降率在4.55%~10.00%,半成品活菌数在（1.82~2.32）×10⁷ 菌落形成单位/mg,成品活菌数在（3.34~4.97）×10⁶ 菌落形成单位/mg,均在老车间历史数据警戒限范围以内。新老车间生产的卡介苗成品的稳定性、卡介菌结构特异性和产品安全性等实验结果均符合相关规定要求。结论  卡介苗生产场地变更未对产品质量产生不利影响。     

不同稳定剂配方的麻疹-腮腺炎-风疹-水痘联合减毒活疫苗的稳定性研究

目的 对比不同冻干稳定剂配方对麻疹-腮腺炎-风疹-水痘联合减毒活疫苗(measles,mumps,rubella and vericella combined live attenuated vaccine,MMRV)稳定性的影响,初步筛选出最佳配方。方法 对比2种含明胶（配方1、2）和1种无明胶冻干稳定剂配方（配方3）对MMRV在37、25及2～8 ℃保存后关键质量指标的影响。结果 37 ℃加速稳定性试验中,仅配方3产品4种病毒滴度均在合格范围内。25 ℃加速稳定性试验中,配方1产品1个月时腮腺炎和水痘病毒滴度即全部低于质量标准下限,配方2、3产品放置6个月,所有4种病毒滴度均在质量标准范围内,但配方2腮腺炎及水痘病毒滴度均处于标准下限。2~8 ℃长期稳定性试验中,配方1产品放置6个月,腮腺炎及水痘病毒滴度均低于质量标准下限,配方2、3产品的病毒滴度稳定性可分别保持18和24个月。结论 针对MMRV开发的无明胶冻干稳定剂配方3在冻干和保存过程中对4种病毒的活性保护效果最佳,其产品有效期至少为2年,并有进一步延长的潜力。研究结果也为日后研发降低明胶使用含量的麻疹系列疫苗冻干稳定剂配方提供了支持。     

扩展CCD动态范围及曲线拼接的一种方法

本文介绍一种通过两次曝光来扩展CCD动态范围及曲线拼接的方法。该方法是用不同的曝光时间,得到两幅灰度值不同的图像,对两幅图中的校准品分别进行曲线拟合。拟合时,使两条曲线有交点,最终将两条曲线拼接为一条连续且单调递增的曲线,这样浓度计算时不会出现跳跃和倒挂。该方法有效地扩大了仪器的检测范围。