基于文本挖掘和生物医学数据库的新型冠状病毒肺炎药物发现

目的 基于文本挖掘技术和生物医学数据库对新型冠状病毒肺炎（COVID-19）相关文献进行数据挖掘分析，探究COVID-19及其主要症状发热、咳嗽、呼吸障碍相关基因靶点，筛选潜在有效的化学药和中药。方法 使用GenCLiP 3网站获取COVID-19和其主要症状咳嗽、发热、呼吸障碍共4个关键词的共有靶点，在METASCAPE数据库中对其进行基因本体（GO）和通路富集分析，再利用String数据库和Cytoscape软件构建共有靶点的蛋白质相互作用网络，筛选获得核心基因，运用DGIdb数据库、SymMap数据库针对核心基因进行中西医治疗药物预测。结果 获得COVID-19及其主要症状共有基因靶点28个，其中有IL2、IL1B、CCL2等核心基因16个，使用DGIdb数据库筛选获得与16个关键靶点相互作用的化学药包括沙利度胺、来氟米特、环孢素等28种，中药包括虎杖、黄芪、芦荟等70味。结论 COVID-19及其主要症状的病理机制可能和CD4、KNG1、VEGFA等28个共有基因相关，可能通过介导TNF、IL-17等信号通路参与COVID-19病理过程。潜在有效药物可能通过作用相关靶点通路起到治疗COVID-19的作用。     

WHO working group meeting to amend WHO Recommendations to assure the quality,safety and efficacy of live attenuated yellow fever vaccines

The current WHO Recommendations to assure the quality, safety and efficacy of live attenuated yellow fever vaccines were adopted in 2010. This document recommends that vaccine virus master and working seed lots should be tested for viscerotropism, immunogenicity and neurovirulence in monkeys. A vaccine manufacturer has reported, recently, discrepancies on the clinical scoring of monkeys during assessment of working seed lots and suggested aligning neurotropism assessment of yellow fever vaccines virus seed lots with that of neurovirulence testing of polio vaccines virus seed lots. In this approach, clinical signs are recorded but do not form part of the assessment or pass/fail criteria. At its 71^st meeting in August 2020, the ECBS agreed to establish a drafting group and to consult with manufacturers and other stakeholders on the proposed amendment. Then a survey had been conducted to seek opinions of stakeholders on the neurotropism testing and revision of current WHO Recommendations for yellow fever vaccines. It was recognized from the answers of the survey that the test for neurovirulence in monkeys presents several technical challenges which could be addressed in the amended version of the Recommendations.On 18–19 March 2021, a virtual WHO working group meeting was held to discuss a proposed draft of the amended text with participants of yellow fever vaccine manufacturers and relevant regulators. Overall, there was a consensus among manufacturers and regulators that clinical evaluation provides important information and should be retained as part of the neurotropism test. However, there was also agreement that the test is somewhat subjective, and that analysis can be difficult. It was recognized that there was potential for improvement in both test execution and analysis to increase harmonization between manufacturers. Alternative tests to the non-human primates neurovirulence test would be useful but it was agreed that none seem to be sufficiently developed at present. Based on these working group discussions, it was proposed that the appendix on neurotropism test to be further revised by the WHO drafting group and submitted to ECBS for review and adoption.Issues other than neurotropism test were discussed in the meeting as well. There were a number of points identified during the meeting, such as new platform of production, animal models, deep sequencing, international standards, that are outside the current recommendations that are worthy of further discussion. Therefore, it is recommended that there would be a future meeting with various stakeholders to discuss the potential revision of the whole Recommendations for yellow fever vaccines in order to meet the current needs.     

发热伴血小板减少综合征研究热点的可视化分析

[摘要]　目的　对发热伴血小板减少综合征（severe fever with thrombocytopenia syndrome, SFTS）的相关文献进行文献计量学和可视化分析，探寻近年来的研究现状、热点及趋势，为临床治疗和基础研究提供参考。方法?以Web of Science（WOS）核心合集和中国知网（China national knowledge infrastructure, CNKI）数据库为文献来源，检索2011年1月1日—2021年12月31日有关SFTS的文献，导入CiteSpace.5.7.R2软件，以国家、作者、文献共被引、关键词为节点进行可视化分析，并绘制相关图谱。结果?在WOS核心合集共检索到797篇文献，在CNKI数据库共检索到714篇文献。相关领域发文量总体呈上升趋势，中国发文量居首位，美国和日本之间机构合作密切。研究热点集中在发病机制、抗体、特异性治疗等领域。非结构蛋白、临床预后、血小板减少、SFTS感染的靶细胞等将是未来的研究重点。结论?国内外关于SFTS的研究逐渐成熟，新型布尼亚病毒、免疫功能、预后是研究重点，但是对SFTS发病机制和病毒受体尚不清楚，仍须进一步探索。     

不同浓度罗哌卡因复合舒芬太尼分娩镇痛对产妇产间发热的影响

目的研究不同浓度罗哌卡因复合舒芬太尼硬膜外注射用于分娩镇痛对产妇产间发热及致热因子的影响。方法适合阴道分娩、自愿要求分娩镇痛的初产妇120例,孕37～41周,年龄20～35岁,ASA I或Ⅱ级,随机分为三组:0.075%罗哌卡因组(A组)、0.1%罗哌卡因组(B组)和0.125%罗哌卡因组(C组),每组40例。宫口扩张至3 cm时实施硬膜外分娩镇痛,A组0.075%罗哌卡因+舒芬太尼0.5μg/ml;B组0.1%罗哌卡因+舒芬太尼0.5μg/ml;C组0.125%罗哌卡因+舒芬太尼0.5μg/ml。记录镇痛后1、2、3、4和5 h、胎儿娩出即刻、分娩后2 h产妇鼓膜温度;分别在镇痛前、胎儿娩出即刻及分娩后2 h采集产妇静脉血,测定血清IL-1β、IL-6、TNF-α浓度;记录产程时间;采用改良Bromage法评定三组产妇在镇痛后1 h及胎儿娩出即刻的运动神经阻滞程度。结果与镇痛前比较,镇痛后5 h及胎儿娩出即刻三组鼓膜温度明显升高,C组发热率明显高于A组和B组(P0.05)。与镇痛前比较,胎儿娩出即刻三组血清IL-1β、IL-6、TNF-α浓度明显升高(P0.05)。C组第二产程和镇痛时间明显长于A组和B组,B组第二产程和镇痛时间明显长于A组(P0.05)。三组运动神经阻滞程度差异无统计学意义。结论不同浓度罗哌卡因复合舒芬太尼硬膜外注射用于分娩镇痛均能产生良好的镇痛效果,低浓度罗哌卡因分娩镇痛产妇发热率低,产妇分娩期间发热与致热因子水平升高相关。     

经方中芍药配伍应用规律探析

考察《伤寒杂病论》经方中配伍应用芍药的61首经方（56首原方，5首加减方）及126条相关条文。通过对经方剂量、比例、配伍、病位主症的分析，认为：经方中芍药为白芍；白芍并非补血药，其益阴补血的功效是通过配伍实现；经方中"分"为计量单位；芍药在丸散汤中的常见用量；经方中芍药主治的症状包括四肢挛急、腹痛、烦满、下利、小便不利等。与不同药物配伍，作用部位与症状随之变化，常见配伍有桂枝、附子、甘草、柴胡、黄芩、枳实、当归、茯苓等。     

Enhanced protection against Q fever in BALB/c mice elicited by immunization of chloroform-methanol residue of Coxiella burnetii via intratracheal inoculation

Human Q fever is recognized as a worldwide public health problem. It often occurs by inhalation of airborne aerosols contaminated with Coxiella burnetii, a gram-negative intracellular bacterium, mainly from domestic livestock. In this study, we analyzed the possibility to establish mucosal and systemic immunity against C. burnetii infection using a pulmonary delivery of chloroform-methanol residue of C. burnetii (CMR) vaccine. Mice were immunized by the intratracheal inoculation of CMR (IT-CMR) or the subcutaneous injection of CMR (SC-CMR), and the immunized mice were challenged with C. burnetii by the intratracheal route. The levels of IFN-γ, IL-12p70, IL-5, and IL-4 in the IT-CMR group in splenic T cells stimulated ex vivo were significantly higher than in the SC-CMR group. Significantly elevated sIgA to C. burnetii was detected in the bronchoalveolar lavage fluid of mice immunized by IT-CMR but not by SC-CMR, which might have contributed to the significant reduction in C. burnetii load and pathological lesions in the lungs of the mice after the challenge of C. burnetii. These results suggest that compared with SC-CMR in mice, IT-CMR was more efficient to elicit cellular and lung mucosal immune responses against aerosol infection of C. burnetii.     

2016 - 2018年泰安市登革热媒介伊蚊监测结果分析

目的 了解泰安市登革热媒介伊蚊种类构成、密度、季节变化，为登革热风险评估提供科学依据。方法 利用布雷图指数(BI)、容器指数(CI)和房屋指数(HI)等指标评价伊蚊幼虫密度， 2016 - 2018年6 - 9月每月各监测1次，对监测结果进行统计学分析。结果 2016 - 2018年平均BI为27.64，CI为16.88%，HI为20.28%。2016 - 2018年3年间白纹伊蚊布雷图指数（BI）呈逐年下降趋势，容器指数（CI）、房屋指数（HI）在3年间呈波动趋势，2018年CI明显高于2016年和2017年，而HI也有上升趋势。2016年BI、CI在8月份最高（BI = 62.79，CI = 32.73%），HI在7月份最高（33.00%）。2017年BI、CI、HI密度高峰均集中在9月份（分别为48.00、24.24%和29.00%）。2018年BI、HI密度高峰在6月份（41.00和34.00%），CI在9月份最高（48.89%）。2016 - 2018年间容器指数差异有统计学意义（χ2 = 29.693，P = 0.000）。不同容器种类的CI差异有统计学意义(χ2 = 29.366，P = 0.000)，其中，废旧轮胎的CI最高（23.81%），其次是闲置容器（20.72%）。闲置容器（碗、瓶、缸、罐）的孳生地构成比最高为66.67%。结论 泰安市白纹伊蚊幼虫密度较高，有明显季节性。做好媒介生物防治知识宣传，加强密度监测，在活动高峰期持续清除孳生地和杀灭成蚊，可有效降低蚊虫密度水平。     

Q fever as a rare cause of hemophagocytic lymphohistiocytosis: Case report

Hemophagocytic Lymphohistiocytosis (HLH) is a reactive disorder of the mononuclear phagocytic system characterized by increased histiocytic proliferation, activation and hemaphagocytosis. The underlying etiology may be genetic (primary) or acquired (secondary). Secondary causes include drugs, autoimmune diseases, malignancies and infections of which EBV is the most common. A 28-year old male patient who was a shepherd with no known concomitant comorbid disease was admitted to the Emergency Department with the complaints of abdominal pain, fever, severe fatigue. Physical examination revealed high fever, hepatosplenomegaly and laboratory examination revealed pancytopenia, hyperferritinemia and hypertriglyceridemia. Hemophagocytes were observed in the bone marrow biopsy and the patient was diagnosed as HLH. The patient was treated with cyclosporine A, dexamethasone, intravenous immunoglobulin (IvIg) and etoposide according to the HLH 2004 protocol. Coxiella burnetii was detected in the serological evaluation of the etiology and doxycycline was added to the current treatment. Fever was controlled in the second week of the treatment and the patient was discharged after complete recovery of the cytopenia in the fourth week. In the outpatient setting, treatment was completed in 8 weeks and follow-up of the patient is still ongoing without medication. To the best of our knowledge, this is the first case from Turkey of HLH secondary to Q-fever which was treated and managed successfully. Since the mortality of HLH is quite high, the etiology should be determined as soon as possible to be able to provide appropriate treatment.     

The potential impact of dengue vaccination with,and without,pre-vaccination screening

BackgroundThe World Health Organization defined a ‘screen and vaccinate’ strategy as its recommended policy for the licensed dengue vaccine (Dengvaxia, Sanofi Pasteur), so that only individuals with previous dengue infection are vaccinated. The objectives of the present study were to build upon a recently published analysis of the benefits and risks associated with dengue vaccination to evaluate the public health impact and cost-effectiveness of a screen and vaccinate strategy.MethodsThe current analysis was based on a previously reported transmission model and added, for the screening part, three rapid diagnostic tests with identical specificity (99%) but alternative sensitivities (50-70-90%) in the detection of prior dengue infection. The impact of a screen-and-vaccinate strategy considered nine settings representing different levels of transmission intensity. Outcomes (dengue-related hospitalizations, severe dengue, and symptomatic dengue) were assessed according to the level of transmission setting. The cost-effectiveness of vaccination in 10 endemic countries was also assessed.ResultsAlthough associated, in most cases, with a lower population impact than a ‘no-screening’ approach, a screen and vaccinate strategy is more effective in reducing the number of hospitalized and severe cases prevented per vaccination performed and generates positive health benefits for individuals screened and subsequently vaccinated. As a result, this intervention is cost-effective in all countries considered except for very low transmission settings. The overall population impact of a screen and vaccinate approach is also likely to be improved by the use of several rounds of screening (up to 48% reduction in dengue hospitalization over 10 years with 5 rounds).ConclusionsWHO recommended option of a screen and vaccinate policy is likely to have a positive impact both at the individual and population level across a wide range of transmission settings and has the potential to be as, if not more, cost-effective than a no screening strategy.