简介:摘要: 本文以CAP1400“国和一号”核电工程中CA01结构模块焊缝为目视检验的对象,介绍并重点分析了目视检验技术在应用过程中存在的“检验空间”和“检验工具”两个影响因素,并从理论和现场实践相结合的角度提出了合理可行的解决方案,从而保证了焊缝的目视检验质量,为后续核电项目中CA01结构模块焊缝的目视检验工作提供借鉴意义。
简介:摘要目的探讨具有广谱中和活性的患者DRVI01血浆来源的HIV-1B′亚型毒株抵抗VRC01抗体中和的机制。方法比较同期感染相同亚型且对VRC01抗体敏感的病毒序列,结合文献报道筛选可能影响VRC01中和作用的关键氨基酸,通过定点突变、不同来源膜蛋白序列交换,验证这些位点氨基酸对VRC01抗体中和作用的影响。结果位于gp120的LoopD区E279D、R282K和V5区N460A、N463Q单点突变,逆转了病毒对VRC01中和敏感性。上述2个或3个位点联合突变后的毒株与单点突变毒株比较,对VRC01抗体中和敏感性明显增强。与文献报道不同,N276糖基化位点突变并未改变毒株对VRC01的敏感性。结论具有广谱中和活性患者DRV01血浆来源的HIV-1B′亚型毒株主要通过LoopD区D279、K282和V5区N460、N463突变,抵抗VRC01抗体的中和作用。
简介:摘要目的了解我国HIV-1 CRF55_01B感染者抗病毒治疗前对蛋白酶类抑制剂(PI)、核苷类逆转录酶抑制剂(NRTIs)、非核苷类逆转录酶抑制剂(NNRTIs)、整合酶抑制剂(INSTIs)的耐药程度以及耐药株的传播关系。方法对2018年全国抗病毒治疗前HIV耐药监测中CRF55_01B重组亚型感染者的血浆样本提取RNA,分别扩增蛋白酶/逆转录酶(PR/RT)区基因片段1 056 bp和整合酶(IN)区基因片段846 bp并测序,利用美国斯坦福大学HIV db Program数据库中全部收录药物进行耐药判定,运用HIV-TRACE软件进行HIV-1耐药传播网络分析,并重点分析了CRF55_01B整合酶基因区遗传多态性位点的突变情况。结果共分析来自全国26个省的178份样本,获得CRF55_01B PR/RT区序列170条以及对应样本的IN区序列170条,总体耐药率为15.3%(26/170)。PIs、NRTIs、NNRTIs、INSTIs耐药率分别为1.2%(2/170)、1.2%(2/170)、15.3%(26/170)、0.6%(1/170);耐药水平多为低度耐药,NNRTIs类耐药位点主要是V179D/E与其他位点协同出现,另有84.1%(143/170)单独携带V179D/E的感染者表现为潜在耐药;INSTIs类耐药位点为G163R,对EVG和RAL表现为低度耐药。在0.9% 最适基因距离阈值下构建分子网络,入网率为30.0%(51/170),耐药株在男男同性传播人群和异性性传播人群之间传播,并且都携带耐药位点E138G和V179E。在整合酶区CRF55_01B与CRF01_AE和B亚型在5个位点突变频率差异较高(T215A、G134N、I135V)。结论我国CRF55_01B感染者抗病毒治疗前即对NNRTIs类药物耐药率较高,携带E138G和V179E耐药位点的毒株存在成簇传播,CRF55_01B整合酶抑制剂耐药株处于低水平流行,但整合酶基因区存在的高突变率的遗传性多态性位点对药物敏感性有潜在的影响,所以新型重组毒株耐药对我国抗病毒治疗的影响还需要进一步监测和分析。
简介:AbstractBackground:Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study.Methods:A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization.Results:V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95% CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively.Conclusions:The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy.Trial Registration:http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx? proj=124702).
简介:摘要目的探讨芳香族抗癫痫药物(AEDs)所致交叉过敏反应与人类白细胞抗原(HLA)-A、B、C、DRB1基因型的相关性。方法采用病例对照研究,将广州市第一人民医院、广州医科大学附属第二医院和暨南大学附属第一医院自2016年9月至2020年9月收集的31例因芳香族AEDs(卡马西平、拉莫三嗪、奥卡西平、苯妥英钠、苯巴比妥)所致交叉过敏反应的患者纳入病例组,52例服用上述5种芳香族AEDs后未出现过敏的患者纳入耐受对照组,500例同期未服用AEDs的健康体检者纳入正常对照组。入组人群均为中国汉族人。采用高分辨率测序法分析3组受试者HLA-A、B、C、DRB1基因型,χ2检验或Fisher确切概率法分析上述基因型与交叉过敏反应的相关性。结果病例组患者HLA-B*13:01的阳性率为45.2%(14/31),耐受对照组患者HLA-B*13:01的阳性率为15.4%(8/52),正常对照组患者HLA-B*13:01的阳性率为14.6%(73/500),病例组患者HLA-B*13:01的阳性率显著高于耐受对照组患者和正常对照组患者,差异有统计学意义(Pc<0.017)。除HLA-B*13:01外,未发现其他HLA-A、B、C、DRB1基因型与芳香族抗癫痫药物导致的交叉过敏反应相关。结论HLA-B*13:01是芳香族AEDs导致交叉过敏反应的危险基因型。