Potential of therapeutic plasmapheresis in treatment of COVID-19 patients: Immunopathogenesis and coagulopathy

Therapeutic plasmapheresis (TP) is the process of the separation and removal of plasma from other blood components and is considered as an adjunctive treatment strategy to the discarded abnormal agent in the management of respiratory viral pandemics. This article reviews the mechanisms of immunopathogenesis and coagulopathy induced by SARS-CoV-2 and the potential benefits of TP as adjunctive treatment in critically COVID-19 patients.     

瓜蒌薤白桂枝汤对老年冠心病患者的临床观察

目的:探究瓜蒌薤白桂枝汤对老年冠心病患者血脂及NT-proBNP、hs-CRP、Fib水平影响。方法:选取2014年4月至2018年4月西藏民族大学附属医院收治的老年冠心病患者78例作为研究对象,根据就诊顺序编号,按照随机数字表法随机分为对照组和观察组,每组39例。对照组常规西医治疗,观察组在对照组基础上加用瓜蒌薤白桂枝汤治疗,同时治疗4周。观察2组治疗前、完成治疗后血脂、NT-pro BNP、hs-CRP、Fib、WBC、HCY、血流流变学、心脏功能水平变化并比较;完成治疗后进行疗效评价。结果:观察组患者治疗后TC、TG、HDL-C、NT-proBNP、hs-CRP、Fib、WBC、HCY、全血高切黏度、全血低切黏度、血浆黏度、红细胞聚集指数下降较对照组患者幅度更低,LDL-C、EDD、NEDD、LVEF、LVPFR上升幅度及治疗后临床总有效率较对照组更高(P<0.05)。结论:瓜蒌薤白桂枝汤能降低老年冠心病患者血脂水平,抑制炎性反应,改善冠状动脉血循环,从而提高疗效,改善心功能。     

PD-L1疫苗中引入不同免疫原性氨基酸对T细胞亚群分化的影响

为了比较内源性的3-硝基酪氨酸与非天然的4-硝基苯丙氨酸在PD-L1疫苗中的引入对T细胞亚群分化的影响，利用遗传密码扩充技术，将这两种免疫原性氨基酸分别引入到PD-L1疫苗的相同位点，获得具有3-硝基酪氨酸以及4-硝基苯丙氨酸的两种PD-L1突变体。用这两种突变体免疫小鼠，分析对小鼠脾脏T细胞亚群分化的影响。流式细胞术检测结果显示，4-硝基苯丙氨酸在PD-L1疫苗中的引入可促进Th1细胞的极化，同时降低Treg细胞的比例，3-硝基酪氨酸的引入对Th1细胞的极化无影响，同时能显著提高Treg和Th17细胞的比例。二者在PD-L1疫苗中的引入均能促进脾脏CD8⁺ T细胞的应答，其中含有4-硝基苯丙氨酸的PD-L1突变体应答效果更强。实验结果表明，与内源性的3-硝基酪氨酸在PD-L1疫苗中的引入相比，非天然的4-硝基苯丙氨酸更适合用于肿瘤疫苗的设计。     

Impact of six years of routine varicella vaccination on the disease-related hospitalizations at Minas Gerais,Brazil

IntroductionThe varicella vaccine was first introduced into the Brazilian immunization schedule in September 2013 as a single dose for children aged 15 months. In 2018, a second dose was recommended for individuals between 4 and 6 years old. This study aims to assess the impact of routine varicella vaccination on the number and profile of hospitalized varicella patients during the single dose period, as well as in the first two years after the adoption of the second dose.MethodsAn observational retrospective study was conducted in an infectious disease pediatric hospital, in Minas Gerais, Brazil. Clinical as well as epidemiological data from patients hospitalized due to varicella between 2010 and 2019 were collected. Patients were split into groups based on the vaccine introduction: pre-vaccine period, single dose and two-dose period. They were compared by age, sex, reason for admission, illness-related complications and clinical outcome.ResultsThere were 1193 admissions due to varicella during the studied period. When compared with the pre-vaccine period, the number of hospitalizations decreased in 61.5% during the single-dose regime, reaching 95.2% in the two-dose period. Hospitalization rates decreased in all age groups, including non-vaccinated individuals such as those younger than 12 months (92.1%). As for reasons of admission, secondary bacterial skin infections were perceived to be the most common cause (>70%). A reduction was also seen in admission of immunocompromised or HIV positive patients (84.8%).ConclusionThe collected data shows a significant impact in the number of hospital admissions due to varicella after six years of the implementation of the vaccine, positively affecting both vaccinated and non-vaccinated individuals. Further reduction was seen after the second dose was initiated, but its true impact will only be understood fully after a longer period of continuous vaccination.     

Design and production of dengue virus chimeric proteins useful for developing tetravalent vaccines

Dengue virus (DENV) is a Flavivirus estimated to cause 390 million infections/year. Currently, there is no anti-viral specific treatment for dengue, and efficient DENV vector control is still unfeasible. Here, we designed and produced chimeric proteins containing potential immunogenic epitopes from the four DENV serotypes in an attempt to further compose safer, balanced tetravalent dengue vaccines.For this, South American DENV isolate sequences were downloaded from the NCBI/Virus Variation/Dengue virus databases and intraserotype-aligned to generate four consensuses. Four homologous DENV sequences were retrieved using BLAST and then interserotype-aligned. In parallel, sequences were subjected to linear B epitope prediction analysis. Regions of the envelope and NS1 proteins that are highly homologous among the four DENV serotypes, non-conserved antigenic regions and the most antigenic epitopes found in the C, prM, E and NS1 DENV proteins were used to construct 11 chimeric peptides. Genes encoding the chimeric proteins were commercially synthesized, and proteins were expressed, purified by affinity chromatography and further subjected to ELISA assays using sera from individuals infected with DENVs 1, 2, 3 or 4. As a proof-of-concept, the chimeric EnvEpII protein was selected to immunize BALB/c and C57BL/6 mice strains. The immunization with EnvEpII protein associated with aluminum induced an increased number of T CD4⁺ and CD8⁺ cells, high production of IgG₁ and IgG₂ antibodies, and increased levels of IL-2 and IL-17 cytokines, in both mouse strains. Because the EnvEpII protein associated with aluminum induced an efficient cellular response by stimulating the production of IL-2, IL-4, IL-17 and induced a robust humoral response in mice, we conclude that it resembles an efficient specific response against DENV infection. Although further experiments are required, our results indicate that epitope selection by bioinformatic tools is efficient to create recombinant proteins that can be used as candidates for the development of vaccines against infectious diseases.     

Immunogenicity of the hepatitis A vaccine 20 years after infant immunization

To determine the duration of immunity provided by the Hepatitis A vaccination (HepA), we evaluated a cohort of participants in Alaska 20 years after being immunized as infants. At recruitment, participants received two doses of inactivated HepA vaccine on one of three schedules. We conducted hepatitis A antibody (anti-HAV) testing for participants at the 20-year time-point. Seventy-five of the original 183 participants (41%) were available for follow-up. The overall anti-HAV geometric mean concentration was 29.9 mIU/mL (95% CI 22.4 mIU/mL, 39.7 mIU/mL) and 50 participants (68%) remained seropositive (titer ≥ 20 mIU/mL). Using a fractional polynomial model, the predicted percent seropositive at 25 years was 55.3%, 49.8% at 30 years and 45.7% at 35 years, suggesting that the percent sero-positive could drop below 50% earlier than previously expected. Further research is necessary to understand if protection continues after seropositivity diminishes or if a HepA booster dose may become necessary.     

参芪降糖颗粒联合二甲双胍对2型糖尿病患者降糖效果的分析

目的：探析2型糖尿病患者采取参芪降糖颗粒联合二甲双胍进行治疗的降糖效果。方法：选取2016年1月至2019年10月马鞍山市中心医院收治的2型糖尿病患者66例作为研究对象，按照随机数字表法分为对照组与观察组，每组33例，对照组通过二甲双胍进行治疗，观察组通过二甲双胍联合参芪降糖颗粒进行治疗，比较2组患者治疗总有效率、血糖参数、不良反应发生率等指标。结果：对照组、观察组的治疗总有效分别为75.76%、93.94%，与对照组比较，观察组的治疗总有效率明显较高（P<0.05）；观察组的空腹血糖、餐后2 h血糖等血糖参数在治疗后明显低于对照组患者（P<0.05）；对照组、观察组的治疗不良反应发生率分别为21.21%、3.03%，观察组治疗不良反应发生率明显低于对照组（P<0.05）。结论：2型糖尿病患者采取参芪降糖颗粒联合二甲双胍进行治疗能够获得较为理想的效果，可明显改善血糖指标，安全性较高，对改善患者的治疗预后有着促进的作用。     

结肠癌T-cadherin表达水平分析与5-Aza-CdR对其表达和结肠癌细胞增殖、侵袭及凋亡的影响

背景与目的：结肠癌是临床常见恶性肿瘤，探讨抑癌蛋白T-cadherin在结肠癌中的表达情况及其与患者临床病理学特征的关系，并分析5-Aza-CdR对T-cadherin表达和结肠癌细胞增殖、侵袭及凋亡的影响。方法：收集福建医科大学附属第二医院2015—2016年40例手术切除的结肠癌组织及癌旁组织新鲜样本，并经过病理学检查验证，分别提取总RNA和总蛋白质。采用实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction，RTFQ-PCR）分析T-cadherin mRNA的表达，采用蛋白质印迹法（Western blot）分析T-cadherin蛋白水平，并分析T-cadherin的mRNA表达变化与患者临床病理学特征的关系。进一步以人结肠癌细胞系HT-29为研究对象，采用甲基化抑制剂5-Aza-CdR处理HT-29细胞，分别采用RTFQ-PCR和Western blot分析T-cadherin表达变化，采用细胞计数试剂盒（cell counting kit-8，CCK-8）分析细胞增殖，采用Transwell实验验证细胞侵袭能力，采用流式细胞术分析细胞凋亡。结果：T-cadherin在结肠癌组织的蛋白水平和mRNA表达均明显低于癌旁组织，其mRNA表达与淋巴结转移（F=5.316，P=0.009 3）和分化程度（F=5.807，P=0.006 4）明显相关，而与其他病理变量（包括性别、年龄、肿瘤大小和肿瘤浸润深度）无明显相关。药物5-Aza-CdR可以显著上调HT-29细胞中T-cadherin的表达水平，抑制HT-29细胞增殖、侵袭并促进细胞凋亡。结论：T-cadherin表达可能与结肠癌恶性程度密切相关，药物5-Aza-CdR处理可上调结肠癌细胞T-cadherin的表达，并抑制结肠癌细胞的增殖、迁移，促进结肠癌细胞凋亡，提示T-cadherin可能是结肠癌患者使用甲基化抑制剂5-Aza-CdR治疗的靶点。     

河北省三种脊髓灰质炎疫苗安全性监测分析

目的 比较河北省二价脊髓灰质炎(脊灰)减毒活疫苗(bivalent oral polio attenuated live vaccine, bOPV)、脊灰灭活疫苗(Salk株)(inactivvated poliomyelitis vaccine made from Salk strains, IPV-Salk)和脊灰灭活疫苗(Sabin株)(inactivated poliomyelitis vaccine made from Sabin strains , IPV-Sabin )接种后疑似预防接种异常反应(adverse events following immunization,AEFI)的发生特征,评价脊灰疫苗的安全性。 方法 通过疑似AEFI信息管理系统收集河北省2016年5月1日—2018年4月30日脊灰疫苗接种后AEFI个案,比较分析三种脊灰疫苗接种后AEFI的报告发生情况。 结果 bOPV、IPV-Salk和IPV-Sabin的AEFI报告发生率分别为13.53 / 10万剂、40.50/10万剂和63.70 / 10万剂。bOPV与IPV-Salk、bOPV与IPV-Sabin、IPV-Salk与IPV-Sabin的AEFI报告发生率(χ²= 360.355, P＜0.001,χ²= 360.247, P＜0.001, χ²= 34.895, P＜0.001)和一般反应报告发生率(χ²= 373.009, P＜0.001, χ²= 564.795, P＜0.001, χ²= 35.382,P＜0.001)差异均有统计学意义,由高到低依次为:IPV-Sabin、IPV-Salk和bOPV;异常反应报告发生率(χ²= 3.077,P=0.079, χ²_C= 1.165,P=0.281, χ²_C= 0,P=1)差异均无统计学意义。三种脊灰疫苗的AEFI中均以一般反应为主,年龄主要集中在≤1岁组,主要发生在接种后1 d内。 结论 河北省三种脊灰疫苗总体安全性良好,但仍需加强脊灰疫苗安全性监测。