Consensus summary report for CEPI/BC March 12–13, 2020 meeting: Assessment of risk of disease enhancement with COVID-19 vaccines

A novel coronavirus (CoV), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China and has since spread as a global pandemic. Safe and effective vaccines are thus urgently needed to reduce the significant morbidity and mortality of Coronavirus Disease 2019 (COVID-19) disease and ease the major economic impact. There has been an unprecedented rapid response by vaccine developers with now over one hundred vaccine candidates in development and at least six having reached clinical trials. However, a major challenge during rapid development is to avoid safety issues both by thoughtful vaccine design and by thorough evaluation in a timely manner. A syndrome of “disease enhancement” has been reported in the past for a few viral vaccines where those immunized suffered increased severity or death when they later encountered the virus or were found to have an increased frequency of infection. Animal models allowed scientists to determine the underlying mechanism for the former in the case of Respiratory syncytial virus (RSV) vaccine and have been utilized to design and screen new RSV vaccine candidates. Because some Middle East respiratory syndrome (MERS) and SARS-CoV-1 vaccines have shown evidence of disease enhancement in some animal models, this is a particular concern for SARS-CoV-2 vaccines. To address this challenge, the Coalition for Epidemic Preparedness Innovations (CEPI) and the Brighton Collaboration (BC) Safety Platform for Emergency vACcines (SPEAC) convened a scientific working meeting on March 12 and 13, 2020 of experts in the field of vaccine immunology and coronaviruses to consider what vaccine designs could reduce safety concerns and how animal models and immunological assessments in early clinical trials can help to assess the risk. This report summarizes the evidence presented and provides considerations for safety assessment of COVID-19 vaccine candidates in accelerated vaccine development.     

"肺炎1号"治疗新型冠状病毒肺炎451例多中心临床研究

目的:观察“肺炎1号”治疗新型冠状病毒肺炎的临床疗效。方法:选取2020年2月17日至2020年3月15日湖北省中医院、监利县中医院、蕲春县人民医院、潜江市中医院、洪湖市中医医院、阳新县中医医院、浠水县中医院、大冶市中医医院、汉川市人民医院、武昌方舱医院收治的新型冠状病毒肺炎患者451例,采用“肺炎1号”联合西医常规治疗,观察“肺炎1号”对新型冠状病毒肺炎患者的临床症状、舌象、实验室检查结果及肺部CT情况。结果:共纳入451例患者,其中轻型21例,普通型378例,重型46例,危重型6例。疑似病例6例(1.33%),临床诊断病例168例(37.25%),确诊病例277例(61.42%)。治疗后与治疗前比较,患者发热、咳嗽、乏力主要症状发生率显著降低(P<0.05);恶寒、鼻塞、流涕、打喷嚏、咽部痒、咽痛、呼吸困难、胸闷、肌肉酸痛或关节疼痛、头晕头痛、纳差、恶心呕吐、腹胀、大便稀溏症状发生率显著改善(P<0.05);白细胞计数、中性粒细胞绝对值变化差异无统计学意义(P>0.05);淋巴细胞绝对值明显升高,差异有统计学意义(P<0.05);C反应蛋白、降钙素原明显降低,差异有统计学意义(P<0.05)。退热时间3(1～3.25)d。229例患者舌质由红或绛逐渐转为淡红,好转率为75.58%;177例患者白腻苔、厚腻苔、黄腻苔明显变薄,好转率为65.31%。新型冠状病毒核酸转阴时间为8(5,11)d。415例(92.02%)肺部CT明显好转,主要表现在病灶面积减小,变薄变淡。达到出院标准430例,临床治愈率95.34%;好转15例;无效3例;死亡3例(0.67%)。治疗过程中,未见明显不良反应,临床应用安全。结论:“肺炎1号”结合西医常规治疗对新型冠状病毒肺炎有较好的治疗作用,能够快速稳定病情,阻断轻型、普通型向重型、危重型转化;明显改善患者临床症状;较好促进肺部炎性反应吸收;使用安全可靠。     

Does perturbation in the mitochondrial protein folding pave the way for neurodegeneration diseases?

Mitochondria, which are cell compartments that are widely present in eukaryotic cells, have been shown to be involved in a variety of synthetic, metabolic, and signaling processes, thereby playing a vital role in cells. The mitochondrial unfolded protein response (mtUPR) is a response in which mitochondria reverse the signal to the nucleus and maintain mitochondrial protein homeostasis when unfolded and misfolded proteins continue to accumulate. Multiple neurodegeneration diseases, including Alzheimer's disease (AD), Parkinson’s disease (PD), and familial amyotrophic lateral sclerosis (fALS), are public health challenges. Every year, countless efforts are expended trying to clarify the pathogenesis and treatment of neurological disorders, which are associated with mitochondrial dysfunction to some extent. Numerous studies have shown that mtUPR is involved in and plays an important role in the pathogenesis of neurological disorders, but the exact mechanism of the disorders is still unclear. Further study of the process of mtUPR in neurological disorders can help us more accurately understand their pathogenesis in order to provide new therapeutic targets. In this paper, we briefly review mtUPR signaling in Caenorhabditis elegans (C. elegans) and mammals and summarize the role of mtUPR in neurodegeneration diseases, including AD, PD and fALS.     

miR-99a对帕金森模型细胞活力及ROS水平的影响

目的:分析miR-99a对帕金森病细胞模型作用。方法:采用Western blotting以及Real-time PCR方法,对miR-99a以及其靶基因FZD5表达水平进行研究。采用CCK-8方法,检测细胞存活力。结果:过表达miR-99a,可将MPP+抑制PC12细胞存活作用明显缓解,该作用是通过调控miR-99a/FZD5轴完成的。结论:miR-99a在帕金森病细胞模型中,可对MPP+导致的PC12细胞存活抑制作用明显缓解,是通过靶向及下调FZD5实现的。     

3D-STI技术联合SYNTAX评分在评价复杂冠心病中的价值

[摘要]目的 探讨实时三维斑点追踪（RT3D-STI）技术联合冠状动脉SYNTAX评分（SS）在评价复杂冠心病患者左室心肌功能中的价值。方法 78例复杂冠心病患者根据SS收集我院拟行冠状动脉造影术（CAG）患者141例，根据CAG影结果分为复杂冠心病组（三支主要冠状动脉和/或左主干狭窄>50%，n=78），非复杂冠心病组（单支/双支主要冠状动脉狭窄>50%，n=30）和对照组（冠状动脉狭窄≤50%，n=33），根据SS将复杂冠心病组分为低分亚组（SS<23，n=26），中分亚组（23≤SS<33，n=25）及高分亚组（SS≥33，n=27）。，应用3D-STI技术获取左心室整体纵向、径向、圆周、三维应变（GLS、GRS、GCS、G3DS）及各节段纵向、径向、圆周、三维应变（LS、RS、CS、3DS），计算平均基底段LS、RS、CS、3DS，中间段LS、RS、CS、3DS，心尖段LS、RS、CS、3DS，行组间比较分析获取相应测值，比较各组间的差异。结果 ①三组间整体、平均节段应变呈减小趋势（P<0.05）。2.三亚组的GLS、GRS、GCS、G3DS呈减小趋势（P<0.05），基底段LS、3DS，中间段LS、RS、CS、3DS，心尖段LS、RS、CS、3DS呈减小趋势LS-BAS、3DS-BAS、LS-MID、RS-MID、CS-MID、3DS-MID、LS-AP、RS-AP、CS-AP、（P<0.05）。②ROC曲线分析示GLS、GCS、GRS、G3DS对不同程度复杂冠心病有一定检测价值，以G3DS及GLS曲线下面积最大。③相关性分析示复杂冠心病组GLS、GCS、GRS、G3DS与冠状动脉SS呈负相关（r=-0.548，-0.366，-0.411，-0.556，P均<0.05）。④重复性检验：3D-STI参数在观察者内及观3DS-AP呈减小趋势（P<0.05）。3.ROC曲线分析：GLS、GCS、GRS、G3DS对不同程度复杂冠心病有一定检测价值，以G3DS及GLS曲线下面积最大。 4.相关性分析：复杂冠心病组GLS、GCS、GRS、G3DS与冠状动脉SS呈负相关（r=-0.548，-0.366，-0.411，-0.556，P均<0.05）。.察者间测量有良好的一致性。结论 RT3D-STI技术可在一定程度上反应复杂冠心病患者的冠状动脉病变程度，联合SYNTAX评分在复杂冠心病的诊断和指导治疗上有一定的积极意义。     

中性粒细胞与淋巴细胞比值对三阴性乳腺癌临床预后及与Ki - 67表达的影响

目的 探讨中性粒细胞与淋巴细胞比值（neutrophil to lymphocyte ratio，NLR）对三阴性乳腺癌的临床预后影响及与Ki - 67表达的关系。方法 回顾性分析2006年1月 - 2012年12月于我院乳腺外科住院治疗的134例三阴性乳腺癌患者。NLR最佳临床分界值采用ROC曲线确定，并依此分NLR＜2.64组和NLR≥2.64组。临床独立预后因素采用单因素和多因素Cox回归模型分析。术后生存时间和生存曲线比较采用Kaplan - Meier和log - rank方法。Ki - 67的表达采用免疫组织化学方法检测。结果 NLR是三阴性乳腺癌的独立预后因素，最佳临界值为2.64。NLR＜2.64组术后中位DFS为39.10月，中位OS为52.30月；NLR≥2.64组术后中位DFS为27.35月，中位OS为37.35月。2组术后DFS和OS比较，差异具有统计学意义（P＜0.05）。NLR低组伴Ki - 67表达阴性的三阴性患者术后中位DFS和OS生存时间显著高于其他情况。结论 NLR是三阴性乳腺癌的关键影响预后因素，具有重复性强、非侵袭性、方便实用等特性，可用于预测三阴性乳腺癌临床预后。     

Effect of multidisciplinary team care on the risk of recurrence in breast cancer patients: A national matched cohort study

BackgroundCancer has been the leading cause of death in the past decade in Taiwan, with breast cancer being the most common type of cancer in females. Very few studies looked at the risk of recurrence in patients who received multidisciplinary team (MDT) care. We analyzed the influence of MDT on the risk of recurrence and death in breast cancer patients.MethodIn this retrospective study, we included newly diagnosed patients from 2004 to 2010. The study included 9,266 breast cancer patients who were enrolled in MDT care and 9,266 patients who were not. The study used log-rank test to analyze patients’ characteristics, hospital characteristics, cancer staging, and treatment methods to compare the recurrence rates in MDT care and non-MDT care participants. We used Cox proportional hazards model to examine the effect of MDT and associated factors on the risk of recurrence and mortality of breast cancer patients.ResultsRelative risk of recurrence was lower for patients who received MDT care than for patients who did not (HR, 0.84; 95%CI: 0.70–0.99) after matching. The mortality risk for breast cancer patients with relapse was 8.48 times (95%CI: 7.53–9.54) than that for patients without relapse.ConclusionsThe relative risk of recurrence and death was significantly lower for breast cancer patients who received MDT care than for those who did not. We suggest that MDT care be implanted in the National Health Policy settings of breast cancer patients.