Adjuvant Systems for vaccines: 13 years of post-licensure experience in diverse populations have progressed the way adjuvanted vaccine safety is investigated and understood

Adjuvant Systems (AS) are combinations of immune stimulants that enhance the immune response to vaccine antigens. The first vaccine containing an AS (AS04) was licensed in 2005. As of 2018, several vaccines containing AS04, AS03 or AS01 have been licensed or approved by regulatory authorities in some countries, and included in vaccination programs. These vaccines target diverse viral and parasitic diseases (hepatitis B, human papillomavirus, malaria, herpes zoster, and (pre)pandemic influenza), and were developed for widely different target populations (e.g. individuals with renal impairment, girls and young women, infants and children living in Africa, adults 50 years of age and older, and the general population). Clearly, the safety profile of one vaccine in one target population cannot be extrapolated to another vaccine or to another target population, even for vaccines containing the same adjuvant. Therefore, the assessment of adjuvant safety poses specific challenges. In this review we provide a historical perspective on how AS were developed from the angle of the challenges encountered on safety evaluation during clinical development and after licensure, and illustrate how these challenges have been met to date. Methods to evaluate safety of adjuvants have evolved based on the availability of new technologies allowing a better understanding of their mode of action, and new ways of collecting and assessing safety information. Since 2005, safety experience with AS has accumulated with their use in diverse vaccines and in markedly different populations, in national immunization programs, and in a pandemic setting. Thirteen years of experience using antigens combined with AS attest to their acceptable safety profile. Methods developed to assess the safety of vaccines containing AS have progressed the way we understand and investigate vaccine safety, and have helped set new standards that will guide and support new candidate vaccine development, particularly those using new adjuvants.Focus on the patientWhat is the context? Adjuvants are immunostimulants used to modulate and enhance the immune response induced by vaccination. Since the 1990s, adjuvantation has moved toward combining several immunostimulants in the form of Adjuvant System(s) (AS), rather than relying on a single immunostimulant. AS have enabled the development of new vaccines targeting diseases and/or populations with special challenges that were previously not feasible using classical vaccine technology.What is new? In the last 13 years, several AS-containing vaccines have been studied targeting different diseases and populations. Over this period, overall vaccine safety has been monitored and real-life safety profiles have been assessed following routine use in the general population in many countries. Moreover, new methods for safety assessment, such as a better determination of the mode of action, have been implemented in order to help understand the safety characteristics of AS-containing vaccines.What is the impact? New standards and safety experience accumulated over the last decade can guide and help support the safety assessment of new candidate vaccines during development.     

基于病因病机分析各省市新型冠状病毒肺炎的中医药防治

新型冠状病毒肺炎属于中医学“疫病”范畴。疫情爆发以来,全国各省市卫生行政管理部门坚持中西医结合原则,陆续制定了各省市的中医药防治方案,三因制宜,分期分型辨证并不断完善。笔者全面收集并整理相关信息,基于病因病机分析了各省市中医药防治方案,认为此次疫病是外感疫气,病位主要在肺卫,病邪主要表现为“毒、湿、热、虚、寒”。此“毒”即为疫气,武汉遇暖冬,非其时而有其气而发疫,一气一病,播散流行,治疫必先治毒;“湿”邪之地在南北方各占一半,东西部均有,在南方源于季节和地域,在北方可由寒挟杂,治疗均应祛湿;“热”主要见于南方,为南方常见的病邪,亦可因湿毒入里,湿郁化热,而在北方热与湿同现,主要是因湿毒入里,湿郁化热,治热均以清为主;“虚”则主要在北方,北方冬季多寒,易伤正致虚,或邪正交争激烈,伤阳伤阴致虚,宜祛邪为标,扶正为本;“寒”见于北方和南方山区,寒气过甚,易伤阳伤正,故尤其要注重预防,且以补正气为主。中医防疫治疫应三因制宜,重视预防,与时俱进。     

糖尿病对脑梗死出血转化及不同分型发生率的影响

目的：探讨糖尿病对脑梗死出血转化及各分型发生率的影响，为临床制定诊疗方案及预后评估提供有价值的资料。方法回顾性分析运城市中心医院及平陆县人民医院神经内科2011年1月—2015年6月间收治的495例临床资料完整的脑梗死住院患者，根据是否有糖尿病将所入选患者分为糖尿病组及非糖尿病组，通过查阅患者影像及临床资料，观察2组住院期间脑梗死出血转化发生率及不同分型出血转化发生率情况。结果糖尿病组153例中发生出血转化76例（49.7%），其中脑实质血肿型21例（13.8%）；非糖尿病组342例中发生出血转化113例（33.0%），其中脑实质血肿型17例（5.0%），2组比较差异具有统计学意义（P<0.01）。结论糖尿病能增加脑梗死出血转化的发生，并能增加更具临床意义的脑实质血肿型出血转化的发生。     

慢性肾病与中医体质相关性的Meta分析*

目的 通过分析慢性肾病中医体质类型的分布情况，探讨慢性肾病与中医体质的相关性。方法 计算机检索中国期刊全文数据库（CNKI）、万方（WANFANG DATA）、中文科技期刊数据库（VIP）、中国生物医学数据库（CBM）、Medline、Embase、The Cochrane Library。收集整理慢性肾病中医体质类型病例对照研究。以Revman 5.3和Stata16软件为工具进行异质性、偏移风险检验与单组率的Meta分析，所有结果以95%可信区间表达效应值。结果 共纳入11项病例对照研究，慢性肾病患者总计1 685例，健康人群总计1 300例。其中气虚质（29.82%）＞血瘀质（22.13%）＞阴虚质（21.53%）＞湿热质（10.95%）。其他6种体质在慢性肾病人群的分布及占有率均小于10%。结论 慢性肾病的发生、发展与气虚、血瘀及阴虚体质的关系最为密切。上述结论可能受纳入原始文献数量和质量等因素限制，而存在偏倚风险，有待进一步深入研究。     

Legionella longbeachae pneumonia: A case report and literature review in Japan

Herein, we report the case of a 74-year-old man diagnosed with Legionella pneumonia detected by Loop-Mediated Isothermal Amplification (LAMP) method, which was suspected to have been transmitted from the potting soil. Legionella longbeachae was identified in the sputum culture. The patient was intubated and maintained on mechanical ventilation. Antimicrobial therapy with azithromycin was also administered. His symptoms were resolved and he was discharged after 26 days of hospitalization. Legionella longbeachae pneumonia rarely occurs in Japan, and published literature of Legionella longbeachae pneumonia cases in Japan was reviewed. Patients with severe pneumonia exposed to potting soils, but with negative urinary antigen test results, should be examined by LAMP method.     

A comprehensive knowledge base of synaptic electrophysiology in the rodent hippocampal formation

The cellular and synaptic architecture of the rodent hippocampus has been described in thousands of peer‐reviewed publications. However, no human‐ or machine‐readable public catalog of synaptic electrophysiology data exists for this or any other neural system. Harnessing state‐of‐the‐art information technology, we have developed a cloud‐based toolset for identifying empirical evidence from the scientific literature pertaining to synaptic electrophysiology, for extracting the experimental data of interest, and for linking each entry to relevant text or figure excerpts. Mining more than 1,200 published journal articles, we have identified eight different signal modalities quantified by 90 different methods to measure synaptic amplitude, kinetics, and plasticity in hippocampal neurons. We have designed a data structure that both reflects the differences and maintains the existing relations among experimental modalities. Moreover, we mapped every annotated experiment to identified potential connections, that is, specific pairs of presynaptic and postsynaptic neuron types. To this aim, we leveraged Hippocampome.org , an open‐access knowledge base of morphologically, electrophysiologically, and molecularly characterized neuron types in the rodent hippocampal formation. Specifically, we have implemented a computational pipeline to systematically translate neuron type properties into formal queries in order to find all compatible potential connections. With this system, we have collected nearly 40,000 synaptic data entities covering 88% of the 3,120 potential connections in Hippocampome.org . Correcting membrane potentials with respect to liquid junction potentials significantly reduced the difference between theoretical and experimental reversal potentials, thereby enabling the accurate conversion of all synaptic amplitudes to conductance. This data set allows for large‐scale hypothesis testing of the general rules governing synaptic signals. To illustrate these applications, we confirmed several expected correlations between synaptic measurements and their covariates while suggesting previously unreported ones. We release all data open‐source at Hippocampome.org in order to further research across disciplines.     

基于文献分析多囊卵巢综合征的中医证型分布及用药规律

目的:通过文献探析中医治疗多囊卵巢综合征(PCOS)的证型分布及临床用药规律。方法:检索2003年至2018年1月1日中国期刊全文数据库(CNKI)、万方、维普3个中文数据库中相关中医治疗PCOS的临床研究文献,建立中医治疗PCOS的整体证型及临床用药数据库,并对数据进行处理、分析。结果:①共纳入符合标准的文献252篇,方剂284首;②涉及证型共37种,其中常见证型为肾虚血瘀证、痰湿证、肾虚痰瘀证,共占43.31%;③涉及病位要素以肾为主,其次为肝、脾;涉及病性要素以血瘀、痰、湿为主;④涉及药物193味,按功效共分为16类,补虚药占41.44%,活血化瘀药占16.20%,化痰祛湿药占14.90%;⑤中医治疗PCOS药性以温、平为主,药味以甘为主,辛、苦次之。结论:PCOS病因病机复杂,以肾虚为本,血瘀、痰湿为标,治疗以补肾活血、化湿祛痰为主。