Compliance to Advisory Committee on Immunization Practices recommendations for pneumococcal vaccination

We evaluated compliance to the ACIP pneumococcal vaccination recommendations issued in 2014 for adults aged ≥ 65 years and in 2012 for adults with high-risk (HR) conditions. The MarketScan® Commercial and Medicare Supplemental databases (January 2007-June 2019) were used to identify the cohorts of interest. Analyses for adults aged ≥ 65 years were adjusted to account for missing vaccination history. Two HR cohorts were identified. The HR1 cohort included patients with immunocompromising conditions, functional or anatomic asplenia, cerebrospinal fluid leak, or cochlear implant. The HR2 cohort included patients with chronic heart, lung, or liver disease; diabetes mellitus; alcoholism; cirrhosis; or cigarette smoking. Full compliance for those aged ≥ 65 years or in the HR1 cohort was defined as receipt of PCV13 and PPSV23, and partial compliance was defined as receipt of PCV13 or PPSV23. For those in the HR2 cohort, full compliance was defined as receipt of PPSV23. Annual compliance rates were estimated using the Kaplan–Meier method.Among those aged ≥ 65 years, partial compliance at 4 years post index was 53% and full compliance was 17% in adjusted analyses. In subjects ≥ 65 years receiving the first vaccination, 42% received the second vaccination by year 4. For the HR1 cohort, partial compliance was 19% and full compliance was 5% at 6 years post index date. For the HR2 cohort, full compliance was 20% at 6 years, with the highest rate in patients with diabetes (27%) and the lowest rate in patients with alcoholism (8%).Additional efforts are needed to maximize compliance to the ACIP pneumococcal vaccine recommendations among adults ≥ 65 years of age and adults with HR conditions including streamlined recommendations and single-dose vaccines. These efforts may subsequently reduce the incidence and burden of pneumococcal disease.     

苓桂术甘汤中多糖结构组成及其抗氧化活性考察

目的:研究苓桂术甘汤中多糖的结构,包括单糖组成以及官能团检测,并对其抗氧化能力进行评估,为体外生物测定法运用于苓桂术甘汤的质量评价提供基础。方法:利用高效凝胶色谱对全方多糖分子量进行研究;进一步采用气相色谱-质谱(GC-MS)柱前衍生化法及红外光谱扫描分析全方多糖结构组成;采用1,1-二苯基-2-三硝基苯肼(DPPH)及羟基自由基测定全方粗多糖及精多糖的抗氧化能力。结果:全方多糖由单一峰组成,且相对分子质量为3 689 Da,主要由阿拉伯糖、甘露糖、葡萄糖、半乳糖、果糖组成,摩尔比为6. 85∶1. 00∶109. 21∶1. 04∶21. 82,其中葡萄糖和果糖为主要组成成分;红外结果显示聚糖结构中存在吡喃糖及糖醛酸,并且糖苷键存在2种立体异构(α-糖苷键及β-糖苷键);抗氧化研究发现全方多糖有一定清除DPPH自由基及羟基自由基的能力,粗多糖的活性优于精多糖。进一步采用LC-Q-TOF-MS对粗多糖中的其他成分进行定性分析,提示这与甘草中五环三萜类成分的吸附有关。结论:苓桂术甘汤中多糖及五环三萜类物质均是苓桂术甘汤抗氧化作用的物质基础,利用体外生物测定法测定抗氧化活性可作为全面控制苓桂术甘汤质量的评价指标。     

麦芽4个化学部位通过多巴胺D2受体对产后缺乳模型大鼠催乳作用研究

目的基于多巴胺D2受体(DRD2),考察小剂量麦芽4个化学部位的催乳作用,初步探讨小剂量麦芽生物碱对产后缺乳模型大鼠泌乳素(PRL)分泌的调节机制。方法采用ig甲磺酸溴隐亭方法制备缺乳大鼠模型,造模成功后,各给药组均ig给予相应的药物,应用ELISA法检测各组大鼠血清PRL、雌二醇(E_2)、孕酮(P)水平;HE染色观察各组大鼠乳腺组织病理改变;采用实时荧光定量PCR(qRT-PCR)法检测各组大鼠脑垂体中泌乳素受体及DRD2 mRNA表达。结果与对照组比较,模型组大鼠血清中PRL、P及E_2水平、脑垂体PRL mRNA表达水平显著降低;脑垂体DRD2 mRNA表达水平显著升高。与模型组比较,麦芽总生物碱组大鼠乳腺小叶体积明显增加,导管明显扩张,且导管及腺泡内含有大量乳汁。麦芽总生物碱明显增加模型大鼠血清中PRL、P、E_2水平及脑垂体PRL mRNA表达水平,降低脑垂体DRD2 mRNA表达水平。结论麦芽催乳的主要药效物质为总生物碱,其作用机制可能与促进PRL分泌,增加脑垂体PRL受体、降低DRD2 mRNA表达水平有关。     

枸杞多糖对酒精性肝损伤小鼠肾脏的保护作用

目的：研究枸杞多糖对酒精性肝损伤小鼠肾脏的保护作用。方法：将60只小鼠随机分为正常对照组，模型组和枸杞多糖低、中、高剂量组（分别为75、150、300 mg/kg）。枸杞多糖组动物连续灌胃受试物16 d，第10天开始，给予枸杞多糖组和模型组50%酒精连续灌胃7 d，建立酒精性肝损伤模型。最后一次灌胃16 h后处死小鼠，取血清和肾脏。用自动生化分析仪检测血清中葡萄糖（GLU）、尿素氮（BUN）和肌酐（CREA）浓度，用生化试剂盒测定肾脏中超氧化物歧化酶（SOD）、谷胱甘肽（GSH）和丙二醛（MDA）浓度，用ELISA方法测定肾脏中肿瘤杀伤因子-α（TNF-α）、白细胞介素-1β（IL-1β）浓度。结果：与对照组相比，模型组小鼠体质量下降，肾脏指数均升高，血清GLU、BUN、CREA浓度升高，肾脏SOD活性、GSH浓度下降，而MDA上升，肾脏炎性因子TNF-α和IL-1β升高（P均< 0.01），表明模型组小鼠在大量酒精刺激后，机体健康受到影响，肾脏受到损伤。与模型组相比，枸杞多糖中剂量组小鼠体质量增加，各剂量组肾脏指数均降低，中、高剂量组小鼠血清GLU浓度（7.63、7.82 mmol/L）降低，高剂量组BUN浓度和CREA浓度降低，而SOD活力升高，各剂量组GSH浓度升高，MDA浓度下降，各剂量组TNF-α浓度降低（P < 0.05），高剂量组IL-β浓度与模型组相比降低（P均< 0.05）。结论：枸杞多糖对于乙醇诱导的小鼠酒精性肾脏损伤具有一定的保护作用。     

健脾方药提取物对小鼠小肠类器官的干预

目的探讨健脾方药四君子汤多糖提取物、黄芪甲苷对小鼠小肠类器官的干预作用。方法取4~6周龄小鼠小肠约20 cm,经过清洗、剪切、消化,分离出小肠隐窝细胞团后,接种于含有多种细胞因子的基质胶中,在基质胶3D结构支撑下,培养形成具有小肠上皮样形态的立体多叶结构,即小肠类器官。光镜下观察小肠类器官的形态特征;采用免疫荧光染色后在激光共聚焦显微镜下观察E-钙黏蛋白(E-cadherin)的表达;传代2天后的小鼠小肠类器官分为3组:对照组、四君子多糖组(终浓度为100 mg/L)以及黄芪甲苷组(终浓度为10μmol/L),继续培养48 h后观察四君子汤多糖提取物、黄芪甲苷对小肠类器官出芽生长及增殖细胞核核抗原Ki-67表达。结果分离出的小鼠隐窝细胞团1天类似囊状,中心具有单个内腔;2~3天开始出芽;4~5天出芽增多,管腔结构进一步清晰,形成小肠类器官,初步建立了小肠类器官培养模式;四君子多糖组(100 mg/L)小肠类器官出芽数量较对照组明显增多(2.31±1.60vs 4.15±1.91,P<0.05);黄芪甲苷组较对照组中小肠类器官Ki-67表达明显增高。结论小肠类器官模型的构建为探讨肠黏膜修复的病理生理机制及药物干预提供了更完善的体外研究模型。四君子汤多糖提取物、黄芪甲苷的肠黏膜保护作用可能与其促进隐窝干细胞更新能力有关。     

兰州百合多糖BHP-1的化学结构与形貌分析

目的:以兰州百合鳞茎中分离和纯化得到的多糖BHP-1为主要研究对象,综合运用仪器分析和化学反应等手段研究其初步的形貌特征和化学结构。方法:采用热重分析(TG)及扫描电镜(SEC)技术分别分析多糖BHP-1的热稳定性和形貌结构特征;通过气相色谱-质谱联用(GC-MS)技术,结合部分酸水解、高碘酸钠氧化-Smith降解以及核磁共振波谱(NMR)分析等方法对多糖BHP-1的化学结构进一步的进行解析。结果:BHP-1是以1,4连接的α-D-吡喃葡萄糖和1,4连接的β-D-吡喃甘露糖为基本骨架的甘露葡聚糖,在葡萄糖和甘露糖的2位和/或3位形成主要的分支,主链或支链的末端残基主要为T-α-D-吡喃葡萄糖,同时在其结构片段中含有少量的O-乙酰基。热重分析显示BHP-1在220℃开始发生降解,520℃基本结束,说明BHP-1热稳定性良好。形貌分析显示BHP-1表面光滑有大量凹陷,凹陷处多为片层结构错落紧密堆积而成,并交织下陷呈不规则的孔洞。结论:多糖BHP-1是一种热稳定性良好,表面光滑有大量的凹陷和孔洞,并含少量O-乙酰基的甘露葡聚糖,其化学结构为首次报道。     

Efficacy,immunogenicity, and safety of available vaccines in children on biologics: A systematic review and meta-analysis

Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics. Response to immunizations in this group is not well known.ObjectiveA systematic review was performed to evaluate three primary outcomes: efficacy; immunogenicity; and safety of vaccines in children with chronic conditions treated with biologics.MethodsThe protocol for our systematic review and meta-analysis was registered and published with PROSPERO. We searched electronic bibliographic databases for studies published from 2009 to 2019, focusing on vaccinations in children with chronic conditions treated with biologics.ResultsWe retrieved 532 records. Thirty-one full-text articles were selected, and 14 were included in the meta-analysis. No significant publication bias was found. Efficacy: limited data are available regarding the efficacy of vaccination, as most studies have focused on immunogenicity as surrogate outcome for efficacy. Immunogenicity: patients receiving anti-TNF-alpha therapy had a statistically significant risk of poor seroconversion (p = 0.028) and seroprotection by the serotype B influenza vaccine [inflammatory bowel disease (IBD) p = 0.013; juvenile idiopathic arthritis (JIA) p = 0.004]. We found adequate responses with H1N1 and H3N2 serotypes. Few studies existed for pneumococcal, hepatitis A virus, hepatitis B virus, varicella-zoster virus, Measles Mumps Rubella virus, and multiple vaccine administration. Safety: vaccine administration was not associated with serious side effects, but JIA patients on anti-TNF alpha therapy had a statistically significant risk of presenting with myalgia or arthralgia postinfluenza vaccine (p = 0.014).ConclusionsMore evidence concerning efficacy, immunogenicity, and safety of vaccinations is needed to guide physicians in the vaccine decision process for this pediatric population.     

Safety data from the MenB-FHbp clinical development program in healthy individuals aged 10 years and older

BackgroundThe MenB-FHbp vaccine (Trumenba®) is licensed in various countries for the prevention of meningococcal serogroup B disease in individuals ≥ 10 years of age. The clinical development program included 11 completed trials where, in each trial, MenB-FHbp had an acceptable safety profile after a primary vaccination series was administered to individuals 10–65 years of age. However, the detection of potential rare events was limited because of individual clinical trial size. The current safety analysis evaluates pooled reactogenicity and other adverse events (AEs) reported in these trials to identify new safety signals not detectable in individual trials.MethodsEleven trials contributed safety data, of which 10 recorded local and systemic reactogenicity events; 8 of the trials were controlled, and reactogenicity data were pooled for 7 of these 8 trials. Additional AE evaluations included immediate AEs (IAEs), medically attended AEs (MAEs), serious AEs (SAEs), newly diagnosed chronic medical conditions (NDCMCs), and autoimmune or neuroinflammatory conditions.ResultsLocal and systemic reactions were more frequent in the MenB-FHbp group (n = 15,294) compared with controls (n = 5509), although most reactions were transient and mild to moderate in severity. Frequencies of IAEs, SAEs, MAEs, NDCMCs, and autoimmune or neuroinflammatory conditions were similar between the MenB-FHbp and control groups.ConclusionsMenB-FHbp demonstrated a favorable safety and tolerability profile in the clinical development program of > 15,000 vaccine recipients ≥ 10 years of age. No new safety signals were identified in the pooled analysis compared with data from the individual trials. Continued postmarketing safety surveillance is important for the identification of rare events.Clinicaltrials.gov: NCT01299480; NCT000808028; NCT00879814; NCT00780806; NCT01352845; NCT01352793; NCT01461993; NCT01323270; NCT01830855; NCT01461980; NCT01768117.     

Lack of effectiveness of 13-valent pneumococcal conjugate vaccination against pneumococcal carriage density in Papua New Guinean infants

BackgroundPapua New Guinea (PNG) introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in 2014, with administration at 1, 2, and 3 months of age. PCV13 has reduced or eliminated carriage of vaccine types in populations with low pneumococcal carriage prevalence, carriage density and serotype diversity. This study investigated PCV13 impact on serotype-specific pneumococcal carriage prevalence, density, and serotype diversity in PNG infants, who have some of the highest reported rates of pneumococcal carriage and disease in the world.MethodsNasopharyngeal swabs were collected at 1, 4 and 9 months of age from PCV13-vaccinated infants (n = 57) and age-/season-matched, unvaccinated infants (at approximately 1 month, n = 53; 4 months, n = 57; 9 months, n = 52). Serotype-specific pneumococcal carriage density and antimicrobial resistance genes were identified by qPCR and microarray.ResultsPneumococci were present in 89% of swabs, with 60 different serotypes and four non-encapsulated variants detected. Multiple serotype carriage was common (47% of swabs). Vaccine type carriage prevalence was similar between PCV13-vaccinated and unvaccinated infants at 4 and 9 months of age. The prevalence of non-vaccine type carriage was also similar between cohorts, with non-vaccine types present in three-quarters of samples (from both vaccinated and unvaccinated infants) by 4 months of age. The median pneumococcal carriage density was high and similar at each age group (~7.0 log₁₀ genome equivalents/mL). PCV13 had no effect on overall pneumococcal carriage density, vaccine type density, non-vaccine type density, or the prevalence of antimicrobial resistance genes.ConclusionPNG infants experience dense and diverse pneumococcal colonisation with concurrent serotypes from 1 month of age. PCV13 had no impact on pneumococcal carriage density, even for vaccine serotypes. The low prevalence of vaccine serotypes, high pneumococcal carriage density and abundance of non-vaccine serotypes likely contribute to the lack of PCV13 impact on carriage in PNG infants. Indirect effects of the infant PCV programs are likely to be limited in PNG. Alternative vaccines with broader coverage should be considered.     

基于网络药理学及分子对接分析丹参黄芪配伍治疗冠心病和心绞痛的活性成分及作用机制

目的：从分子水平研究丹参黄芪配伍抗冠心病和心绞痛的分子机制。方法：采用中药系统药理学数据库和分析平台（Traditional Chinese Medicine Systems Pharmacology，TCMSP）获取丹参和黄芪活性成分，基于CTD （Comparative Toxicogenomics Database，比较毒物基因组学数据库）筛选冠心病和心绞痛的关键靶标。借助STRING软件对心绞痛和冠心病的靶标基因进行相互作用分析，基于分子对接（Sybyl2.1）对筛选所得的丹参、黄芪的活性成分与心绞痛及冠心病靶点进行分子对接验证。借助Cytoscape3.5.1构建"活性成分-靶点"网络模型。结果：丹参黄芪共筛选出61个活性成分，其中丹参44个，黄芪17个。筛选出冠心病靶标25个，心绞痛靶标7个，通过靶蛋白PPI网络分析，肿瘤坏死因子、基质金属蛋白酶-9、Toll样受体4、载脂蛋白E、脂肪酸转运蛋白、血管紧张素Ⅰ转化酶、基质金属蛋白酶-3、尿激酶为冠心病和心绞痛疾病的关键靶标蛋白。分子对接发现黄芪单味药、丹参单味药、黄芪丹参配伍用药可能通过调节尿激酶（PLAU）、载脂蛋白E （APOE）、血管紧张素I转化酶（ACE）发挥抗冠心病及心绞痛的作用。结论：从分子层面筛选丹参黄芪配伍治疗冠心病、心绞痛疾病的关键活性成分及靶点，为其配伍后实验研究和临床应用提供合理解释。