Immunogenicity and safety of two novel human papillomavirus 4- and 9-valent vaccines in Chinese women aged 20–45 years: A randomized,blinded, controlled with Gardasil (type 6/11/16/18), phase III non-inferiority clinical trial

BackgroundHuman papillomavirus (HPV) infections were the main cause of anogenital cancers and warts. HPV 6/11/16/18 vaccines provide protection against the high-risk types of HPV responsible for 70% of cervical cancers and 90% of genital warts. This randomized, blinded, non-inferiority phase III trial was to determine whether immunogenicity and tolerability would be non-inferior among women after receiving two novel 4- and 9-valent HPV vaccines (4vHPV, HPV 6/11/16/18; 9vHPV, HPV 6/11/16/18/31/33/45/52/58) compared with those receiving Gardasil 4 (4-valent).Methods1680 females between 20 and 45 years were randomized in a 2:1:1 ratio to 20–26, 27–35, or 36–45 y groups. Subjects then equally assigned to receive 4vHPV, 9vHPV or Gardasil 4 (control) vaccine at months 0, 2, and 6. End points included non-inferiority of HPV-6/11/16/18 antibodies for 4vHPV versus control, and 9vHPV versus control and safety. The immunogenicity non-inferiority was pre-defined as the lower bound of 95% confidence interval (CI) of seroconversion rate (SCR) difference > ?10% and the lower bound of 95% CI of geometric mean antibody titer (GMT) ratio > 0.5.ResultsAmong the three vaccine groups, more than 99% of the participants seroconverted to all 4 HPV types. The pre-specified statistical non-inferiority criterion for the immunogenicity hypothesis was met: all the lower bounds of 95% CIs on SCR differences exceeded ?10% for each vaccine HPV type and the corresponding lower bounds of 95% CIs for GMT ratios > 0.5. Across vaccination groups, the most common vaccination reaction were injection-site adverse events (AEs), including pain, swelling, and redness. General and serious AEs were similar in the three groups. There were no deaths.ConclusionsThis study demonstrated that the novel 4- and 9-valent HPV vaccination was highly immunogenic and generally well tolerated, both of which were non-inferior to Gardasil 4 in immunogenicity and safety.     

流行病学思维方法在全科医生培养中的应用研究

目的 流行病学是公共卫生的主干学科,也是一门广泛应用于其他学科的应用科学。全科医学以人的健康为中心,在疾病预防与健康管理方面具有重要作用,是居民健康的“守门人”。分析流行病学思维方法在全科医生培养中的应用意义,为我国全科医学教育的进一步发展提供启示。 方法 以“流行病学”“全科医学”“全科医生”“家庭医生”“全科团队”和“全科医学教育”为关键词,对中国知网、万方数据库、维普及Pubmed数据库中1990年以来近30年的文献进行分析,结合我国全科医学教育现状,总结和分析流行病学思维方法在全科医生培养中的主要结合点。 结果 目前全科医生培养过程中融入流行病学思维方法的教学理念与方法不足,应将预防为主的大健康理念贯穿于全科医生教育和工作中,并增加突发公共卫生疫情防控协调处置技能训练,突出流行病学三级预防理念、流行病学调查在全科医生培养中的融合效果。 结论 应将流行病学的思维方法融入到全科医学教育与实践全过程之中,培养具有大健康观念、能维护和促进居民健康的全科医生。      

左归丸治疗卵巢早衰小鼠处方配比研究

目的对左归丸治疗卵巢早衰作用进行拆方研究,明确该方配伍的科学性。方法以免疫性卵巢早衰小鼠为模型,采用均匀设计方法。将左归丸拆方为不同组方,观察各组方对模型小鼠卵巢细胞的凋亡率降低的效果。结果方中熟地、炒山药、川牛膝均是影响细胞凋亡的主要因素．选择左归丸治疗卵巢早衰的最优配方为熟地：炒山药：川牛膝（18：9：9）。结论优选后的配比与传统中药方解较为一致．配比可行。为本方的药理研究和临床应用提供剂量依据。     

电位滴定法测定肿节风注射液中总有机酸含量

目的 建立肿节风注射液中总有机酸含量的测定方法.方法 采用电位滴定法进行含量测定.结果 6个批次的肿节风注射液总有机酸含量(以反丁烯二酸计)每支在3.06～3.16 mg之间,RSD=1.20％ (n=6),反丁烯二酸加样回收率为96.28％～101.56％.结论 该方法简便快速,精密度好,准确度高,重现性好可以作为肿节风注射液中总有机酸的质量控制方法之一.     

富集纯化前上样液参数影响三七皂苷类成分的研究

目的 考察富集纯化前上样液参数pH值、氯化钠浓度、时间等对三七皂苷类成分的影响.方法 用UV、TLSC分别测定3种不同上样液在不同时间段的三七总皂苷、人参皂苷Rg1、人参皂苷Rb1、三七皂苷R1的含量.结果 3种上样液放置72 h后,人参皂苷Rg1含量均增加(P＜0.01);三七皂苷R1含量均减少(P＜0.05);人参皂苷Rb含量变化无差异;pH5.5上样液和pH 7.0上样液中的总皂苷含量均增加(P＜0.05),pH5.5且含4％氯化钠的上样液中总皂苷含量无明显变化.结论 在富集纯化过程中,上样液的pH值、无机盐浓度和时间对皂苷类成分含量变化有影响.     

No increased risk of Guillain-Barré syndrome after human papilloma virus vaccine: A self-controlled case-series study in England

ObjectiveTo investigate the risk of Guillain-Barré syndrome (GBS) after human papilloma virus (HPV) vaccine given to 12–18 year old girls in England.MethodsHospital Episode Statistics (HES) were searched using data to March 2016 to identify incident cases of GBS in female patients aged from 11 to 20 years eligible to have received the HPV vaccine since its introduction as a 3 dose schedule in September 2008. Diagnosis was confirmed by the case’s general practitioner (GP) who also provided HPV vaccination dates. The risk of admission within 3 months (primary risk window) 6 and 12 months of any dose was assessed using the self-controlled case-series (SCCS) method in vaccinated girls with age, season and time-period adjustment. The risk before and after the change in 2012 from bivalent vaccine to quadrivalent vaccine was also assessed.ResultsA total 244 episodes were initially identified which reduced to 101 episodes in 100 girls when just including cases where the GP could be contacted, at least one vaccine dose was given, and GBS was confirmed or classed as probable. Nine, 14 and 24 GBS admissions occurred within 3, 6, 12 months of a dose respectively. The relative incidence (RI) for the 3 month risk period was 1.04 (95% confidence interval 0.47–2.28), for the 6 month period 0.83 (0.41–1.69) and for the 12 month period 1.10 (0.57–2.14). When restricting to 79 confirmed cases the RI in the 3 month risk period was 1.26 (0.55–2.92) and the RI 1.61 (0.39–6.54) for quadrivalent vaccine compared to 0.84 (0.30–2.34) for bivalent.ConclusionWe found no evidence of an increased risk of GBS following HPV vaccination in England and, based on the upper end of the 95% CI for the RI and the number of HPV vaccine doses given in England, can exclude a risk of about 1 per million doses.     

荔枝核皂苷对糖调节受损大鼠胰腺组织氧化应激的改善作用及其机制

目的：研究荔枝核皂苷（SL）对糖调节受损（IGR）大鼠氧化应激及核转录因子E2相关因子2（Nrf2）/血红素加氧酶1（HO-1）信号通路的作用,阐明其相关机制。方法：采用高脂饲料喂养制备IGR大鼠模型,随机分为模型组、二甲双胍组（0.20 g·kg^-1）、低剂量SL组（0.05 g·kg^-1）、中剂量SL组（0.10 g·kg^-1）和高剂量SL组（0.20 g·kg^-1）,同时设正常对照组,每组12只,连续给药6周。观察SL对实验大鼠糖脂代谢的影响,采用实时荧光定量（Real-time PCR）法检测大鼠胰腺组织中超氧化物歧化酶（SOD）、丙二醛（MDA）和HO-1 mRNA表达水平,Western blotting法检测大鼠胰腺组织胞核、胞质Nrf2和全细胞HO-1蛋白表达水平,采用SOD和MDA试剂盒检测大鼠胰腺组织中SOD活性和MDA水平。结果：与正常对照组比较,模型组大鼠空腹血糖（FBG）和血脂水平明显升高（P<0.05或P<0.01）,胰腺组织中SOD活性和mRNA表达水平降低（P<0.01）,MDA水平和mRNA表达水平升高（P<0.01）,胞核和胞质中Nrf2蛋白表达水平和核转位率升高（P<0.01）,HO-1 mRNA和蛋白表达水平升高（P<0.05或P<0.01）。与模型组比较,二甲双胍组和中、高剂量SL组大鼠FBG和血清甘油三酯（TG）水平明显降低（P<0.05或P<0.01）,胰腺组织中SOD活性和mRNA表达水平升高（P<0.05或P<0.01）,MDA水平和mRNA表达水平降低（P<0.05或P<0.01）,胞质中Nrf2表达水平降低（P<0.05或P<0.01）,胞核中Nrf2表达水平和核转位率升高（P<0.05或P<0.01）,HO-1 mRNA和蛋白表达水平升高（P<0.05或P<0.01）。结论：SL具有改善糖脂代谢和增强抗氧化应激作用,其作用机制可能与激活Nrf2/HO-1信号通路、促进Nrf2核转位及增强下游抗氧化基因HO-1表达有关。     

四价人乳头瘤病毒疫苗在中国境内9~26岁女性中的免疫原性和安全性研究：一项开放性、免疫桥接Ⅲ期临床试验

目的四价人乳头瘤病毒疫苗(quadrivalent human papillomavirus,qHPV;HPV6/11/16/18型,临床试验注册号NCT03493542)于2017年在中国境内获批上市,适用于20~45岁女性。这项开放性Ⅲ期临床试验旨在评估并比较9~19岁和20~26岁中国境内女性四价HPV疫苗自第1剂接种至第7个月的免疫原性和安全性。方法9~26岁的受试者分别于第1天、第2个月和第6个月接种3剂次四价HPV疫苗。使用竞争性荧光免疫检测法(cLIA)分析首剂接种当天和第7个月时受试者血清样本中的抗-HPV6/11/16/18抗体几何平均滴度(GMT)和血清抗体阳转率。记录接种后30 d内的注射部位不良事件和全身性不良事件以及整个研究期间出现的严重不良事件。结果本研究共纳入766例接种至少1剂受试者(9~19岁组与20~26岁组各383例)。两个年龄组中所有符合免疫原性方案的受试者在第7个月时,疫苗所含四种HPV型别均产生血清学抗体阳转。9~19岁年龄组受试者在第7个月时产生的抗-HPV6/11/16/18 GMT值非劣效于20~26岁组受试者。9~19岁年龄组中,分别有36.6%和49.3%的受试者报告注射部位不良事件和全身性不良事件,20~26岁年龄组受试者中注射部位和全身性不良事件比例分别为40.7%和54.8%。没有发生疫苗相关严重不良事件。无受试者因不良事件终止研究,无死亡病例的报告。结论9~19岁中国境内女性中接种3剂次四价HPV疫苗后产生的抗体水平非劣效于20~26岁年龄组。该疫苗在研究人群中具有良好的耐受性。     

The effect of physical activity on long-term income

Empirical evidence for the direct effects of physical activities on long-term labor market outcomes is limited. This state of affairs is surprising, because there is a growing amount of support on the positive effects of physical activities on health on the one hand and on the effects of good health on labor market outcomes on the other hand. We examine the long-term income effects of physical activity using a large sample (N = 5042) of male twins from Finland (Older Finnish Twin Cohort Study, 1975, 1981, 1990), matched to detailed register-based income data (Finnish Longitudinal Employer-Employee Data, 1990–2004). Our primary income measure is calculated over a fifteen-year period and it covers the prime working age of the twins that we study. We use the twin dimension of the data to control for unobservable genetic and family confounding factors. Our within-twin estimates show that being physically active has a positive impact on the long-term income. We argue that our results are not easily reconciled with the intuitive explanation of physical activity enhancing long-term income via health or more intense labor market attachment. We reason that instead, there may be various non-cognitive mechanisms at work: Physical activity can, for example, make people more persistent in the face of work-related difficulties and increase their desire to partake in competitive situations, with greater expected pecuniary rewards.     

D101型大孔树脂纯化附子生物碱

目的:研究附子生物碱经D101型大孔树脂富集后化学成分的变化.方法:以附子中总生物碱、酯型生物碱、乌头碱、次乌头碱及新乌头碱的转移率为指标,采用UV,HPLC,TLC分别对富集前后附子提取物中的生物碱进行含量测定及其成分鉴别.结果:采用D101型大孔树脂富集附子生物碱,总生物碱转移率83.70％,纯度67.34％;乌头碱转移率77.78％,次乌头碱转移率94.12％,新乌头碱转移率52.63％;TLC比较发现显示6个相似的生物斑点,说明富集前后生物碱化学成分无明显差异.结论:D101型大孔树脂能有效提高附子中总生物碱的纯度,且各生物碱转移率较高,可用于大生产推广.