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。     

黄热病的再流行与世界卫生组织的消除黄热病流行战略

近年来,蚊虫传播的黄热病在非洲和南美洲地区大面积“再流行”,仅南美洲的巴西在一年时间就发现数千例黄热病确诊病例,黄热病已经在非洲和南美洲地区造成巨大的公共卫生负担。此外,在黄热病非流行国家和地区发现大量输入性病例,使得黄热病有可能在非洲和南美洲以外的地区成为“新发传染病”而在世界更大范围流行。为此,世界卫生组织制定了“消除黄热病流行（EYE）”战略,预计利用10年时间在黄热病流行地区接种13.8亿剂量黄热疫苗,以降低黄热病对国际公共卫生健康的危害。     

Effect of a Device-Free Compressed Shell Fixation Method on Hepatic Respiratory Movement: Analysis for Respiratory Amplitude of the Liver and Internal Motions of a Fiducial Marker

Purpose

Suppression of respiratory movement of the liver would be desirable for high-precision radiation therapy for liver tumors. We aimed to investigate the effect of our original device-free compressed shell fixation method and breathing instruction on suppression of respiratory movement. The characteristics of liver motion based on the movement of a fiducial marker were also analyzed.

The efficacy and toxicity of immune checkpoint inhibitors in a real-world older patient population

ImportanceImmunotherapy has emerged as an effective treatment option for the management of advanced cancers. The effects of these immune checkpoint inhibitors in the older patient population has not been adequately assessed.ObjectiveTo understand the impact of aging on CTLA-4 and PDL-1 inhibitors efficacy and immune-related adverse events (irAE) in the context of real-world management of advanced solid cancers.Design, Setting, and ParticipantsThis retrospective study involved all non-study patients with histologically-confirmed metastatic or inoperable solid cancers receiving immunotherapy at Kingston Health Sciences Centre. We defined ‘older patient’ as age ≥ 75. All statistical analyses were conducted under SPSS IBM for Windows version 24.0.Main Outcomes and MeasuresStudy outcomes included immunotherapy treatment response, survival, as well as number, type, and severity of irAEs.ResultsOur study (N = 78) had 29 (37%) patients age <65, 26 (33%) patients age 65–74, and 23 (30%) patients age ≥75. Melanoma, non-small cell lung cancer, and renal cell carcinoma accounted for 70%, 22%, and 8% of the study population, respectively. Distributions of ipilimumab (32%), nivolumab (33%), and pembrolizumab (35%) were similar in the study. The response rates were 28%, 27%, and 39% in the age <65, age 64–74, age ≥75 groups, respectively (P = 0.585). Kaplan-Meier curve showed a median survival of 28 months (12.28–43.9, 95% CI) and 17 months (0–36.9, 95% CI) in the age <65 and age 64–74 groups, respectively; the estimated survival probability did not reach 50% in the age ≥75 group (P = 0.319). There were no statistically significant differences found in terms of irAEs, multiple irAEs, severity of grade 3 or higher, types of irAEs, and irAEs resolution status when comparing between different age groups.Conclusion and RelevanceOur results suggest that patients age ≥75 are able to gain as much benefit from immunotherapy as younger patients, without excess toxicity. Our findings suggest that single agent immunotherapy is generally well-tolerated across different age groups with no significant difference in the type, frequency or severity of irAEs. Future studies evaluating aging and combination immunotherapy are warranted.     

南宁市江南区2019年登革热流行病学特征和疫情应急处置分析

目的 分析总结南宁市江南区2019年登革热流行病学特征和疫情应急处置的工作情况,为今后有效地防制登革热提供对策、参考和技术支持。方法 收集南宁市江南区2019年登革热疫情相关数据,评价本次应急处置的工作成效。结果 2019年南宁市江南区登革热疫情严峻,共报告登革热病例370例,其中输入病例4例,本地病例366例;感染人数以家务待业和离退休者居多;男女性别比为1∶1.12;发病年龄最小1岁,最大92岁;发病的空间分布呈现高度聚集,福建园街道占本城区本地病例的87.70%。早期伊蚊应急监测布雷图指数和账诱指数合格率偏低,分别为72.17%和62.61%。针对本次疫情特性,制定有针对性的防控策略,做好精准疫情应急处置,有效压低峰值,迅速控制了疫情的扩散和蔓延。结论 本次疫情是由输入性病例导致本地病例社区水平暴发,疫情呈现多点暴发及扩散蔓延态势。需做好疫情研判、预警预测,准确分析流行病学特征,尽早实施登革热应急处置,精准防控、孳生地处理、健康宣教和病例管理是应急处置的关键措施。     

Ebola Virus RNA Stability in Human Blood and Urine in West Africa’s Environmental Conditions

We evaluated RNA stability of Ebola virus in EDTA blood and urine samples collected from infected patients and stored in West Africa’s environmental conditions. In blood, RNA was stable for at least 18 days when initial cycle threshold values were <30, but in urine, RNA degradation occurred more quickly.     

An Environmental Scan of the National and Provincial Diagnostic Reference Levels in Canada for Common Adult Computed Tomography Scans

Several regulatory bodies have agreed that low-dose radiation used in medical imaging is a weak carcinogen that follows a linear, non-threshold model of cancer risk. While avoiding radiation is the best course of action to mitigate risk, computed tomography (CT) scans are often critical for diagnosis. In addition to the as low as reasonably achievable principle, a more concrete method of dose reduction for common CT imaging exams is the use of a diagnostic reference level (DRL). This paper examines Canada's national DRL values from the recent CT survey and compares it to published provincial DRLs as well as the DRLs in the United Kingdom and the United States of America for the 3 most common CT exams: head, chest, and abdomen/pelvis. Canada compares well on the international scale, but it should consider using more electronic dose monitoring solutions to create a culture of dose optimization.     

Molecular characterization of the 17D-204 yellow fever vaccine

IntroductionThe worldwide use of yellow fever (YF) live attenuated vaccines came recently under close scrutiny as rare but serious adverse events have been reported. The population identified at major risk for these safety issues were extreme ages and immunocompromised subjects. Study NCT01426243 conducted by the French National Agency for AIDS research is an ongoing interventional study to evaluate the safety of the vaccine and the specific immune responses in HIV-infected patients following 17D-204 vaccination. As a preliminary study, we characterized the molecular diversity from E gene of the single 17D-204 vaccine batch used in this clinical study.Materials and methodsEight vials of lyophilized 17D-204 vaccine (Stamaril^®, Sanofi-Pasteur, Lyon, France) of the E5499 batch were reconstituted for viral quantification, cloning and sequencing of C/prM/E region.ResultsThe average rate of virions per vial was 8.68 ± 0.07 log₁₀ genome equivalents with a low coefficient of variation (0.81%). 246 sequences of the C/prM/E region (29–33 per vials) were generated and analyzed for the eight vials, 25 (10%) being defective and excluded from analyses. 95% of sequences had at least one nucleotide mutation. The mutations were observed on 662 variant sites distributed through all over the 1995 nucleotides sequence and were mainly non-synonymous (66%). Genome variability between vaccine vials was highly homogeneous with a nucleotide distance ranging from 0.29% to 0.41%. Average p-distances observed for each vial were also homogeneous, ranging from 0.15% to 0.31%.ConclusionThis study showed a homogenous YF virus RNA quantity in vaccine vials within a single lot and a low clonal diversity inter and intra vaccine vials. These results are consistent with a recent study showing that the main mechanism of attenuation resulted in the loss of diversity in the YF virus quasi-species.