艾滋病的流行情况和危险因素与预防进展

艾滋病疫情的特征是人类免疫缺陷病毒(HIV)特异性地攻击CD4⁺T淋巴细胞,导致患者出现各种机会性感染或肿瘤,从而造成获得性免疫缺陷功能障碍(AIDS)。当前我国的艾滋病疫情处于总体低流行状况,疫情地区分布差异大,性传播逐渐成为主要传播途径,艾滋病疫情上升速度有所减缓,但是流行因素依然存在。同时我国科研与卫生工作者针对我国的艾滋病做了大量的工作,譬如已经进行了大量的流行病调查与科研前期分析,开发了一些前期用药,了解了多数艾滋病高发地区的疫情状况,但是存在一定的不足。本文综述了艾滋病的流行情况,深入阐述了艾滋病的危险因素与传播方式,重点论述了艾滋病的预防进展,包括心理干预、夫妻支持和社会支持等,希望为艾滋病的早诊断、早治疗提供帮助。     

2009—2019 年重庆市涪陵区15 岁以下人群流感病原学监测结果分析

目的 了解重庆市涪陵区2009—2019年15岁以下人群流感病原学的流行趋势及特征,为今后的流感防控工作提供科学依据。方法 分析2009—2019年涪陵区流感网络监测实验室获得的15 岁以下人群流感样病例（Influenza-like illness,ILI）监测结果。结果 女性ILI病毒分离阳性率（14.53%）和男性阳性率（13.74%）无统计学意义（〖XC小五号.EPSP〗=0.98,P＞0.05）;初中生阳性率最高（23.94%）,其次是小学生（19.69%）、幼儿园儿童（17.10%）,散居儿童最低（7.64%）,差异有统计学意义（〖XC小五号.EPSP〗=238.82,P＜0.05）;各学龄段儿童之间流感病毒类型构成差异有统计学意义（〖XC小五号.EPSP〗=40.71,P＜0.05）;ILI病毒检测阳性率的季节规律呈单、双峰交替出现,2010 年、2014 年、2015 年流行高峰出现在夏季,其余年份流行高峰均在冬春季;主要病原学类型为季H3（36.63%）、B型Victoria系（28.60%）、新甲H1（27.98%）、B型Yamagata系（6.44%）,流感病毒阳性率与ILI病例数变化趋势相关（rs=0.312,P＜0.05）; ILI发病后采样时间、采样后送检时间对标本阳性率有显著影响。结论 涪陵区15岁以下人群流感流行处于上升趋势,流行高峰时间处于动态变化,近年来主要在冬春季;初中生和小学生ILI病毒检测阳性率高于学龄前儿童,提示冬春季要加强中小学校学生流感防控工作。     

2020年宁夏新冠疫情期间SARS-CoV-2与常见发热呼吸道病原流行特征比较分析

目的 了解2020年宁夏新冠疫情期间SARS-CoV-2与常见6种发热呼吸道病原的检出情况、流行规律和感染特点,为新冠疫情常态化防控提供理论依据。方法 应用Real time RT-PCR技术对2020年1月20日至2020年2月16日期间宁夏疾病预防控制中心收检的COVID-19筛查样本进行SARS-CoV-2和Flu等常见发热呼吸道病原进行定性检测,并收集各病原阳性患者人口学特征资料。结果 529例COVID-19筛查样本中,SARS-CoV-2阳性检出率为13.23%（70/529）。对COVID-19筛查样本中180份符合条件的FRS病例样本进行6种其他呼吸道病毒病原检测,阳性检出率为12.78%（23/180）,其中检出率较高的病原为Flu和HRSV,阳性率分别为5.00%和2.78%。各时间段内SARS-CoV-2阳性检出率存在两个较为明显的峰值,其他呼吸道病毒总阳性检出率稳中有降。SARS-CoV-2阳性检出率男性和女性差异无统计学意义,41~ 60岁组及60岁以上组阳性率较高,分别为25.00%和24.39%,阳性病例在宁夏五市均有分布,银川市最多;其他呼吸道病原男性检出率显著高于女性,41~ 60岁组阳性率最高,其次为0~20岁组,阳性率分别为33.33%和12.20%,阳性主要集中于银川与中卫两市。结论 在常态下防控新冠疫情的背景下,应加强呼吸道传播病原快速筛查体系的建设以达到精准防控传染病的迫切需求。     

Effective improvements to the live-attenuated Newcastle disease virus vaccine by polyethylenimine-based biomimetic silicification

Live and killed vaccines impart a significant role in preventing of Newcastle disease (ND) in China. Vaccine efficacy could be ameliorated by improving vaccine-induced cellular immunity and antibody persistency. Previous studies substantiated the potency of silicon dioxide (SiO₂) in the control-release of drugs and as a vaccine adjuvant, and polyethylenimine (PEI) merits as a mucosal adjuvanticity with electro-positivity. The present study employed SiO₂ and PEI to prepare biomimetic silicon mineralized nanoparticle G7M@SiO₂-PEI and microparticle (SiO₂ + PEI)@G7M vaccines of G7M, a candidate for live attenuated vaccine of genotype VII Newcastle disease virus (NDV). The zeta potential experiment confirmed the significant increase in the average zeta potential of the nanoparticle G7M@SiO₂-PEI and microparticle (SiO₂ + PEI)@G7M relative to G7M before mineralization. The results of RT-qPCR revealed more than 99% mineralization efficiency of the G7M@SiO₂-PEI and (SiO₂ + PEI)@G7M. The morphology detected by transmission electron microscopy reported that the diameters of G7M@SiO₂-PEI were similar to those of G7M, while for (SiO₂ + PEI)@G7M, it was about five times larger than that of G7M. Silicon was detected on the surface of both mineralization particles, except for G7M, as observed from the elemental distribution detected by elemental mapping and energy dispersive X-ray spectrogram. Indirect immunofluorescence assays validated that mineralization virus have replicated ability in BHK-21F cells. In vivo experiments revealed higher than 5.50 log₂ of antibody in nanoparticles G7M@SiO₂-PEI group until 10-week post-vaccination, and significant proliferation of antigen-specific CD3⁺CD4⁺ in nanoparticles G7M@SiO₂-PEI immunized group corroborated improved cellular immune responses. Vaccines provided full protection to the immunized chickens, whereas all the chickens receiving mock immunizations succumbed to the disease. Overall, our study concluded the efficacy of biomimetic mineralization of live attenuated vaccine in nanoparticles to improve humoral and cellular immune responses.     

Sendai virus particles carrying target virus glycoproteins for antibody induction

Induction of antibodies targeting viral glycoproteins is a key for the development of a vaccine against enveloped virus infection. Glycoproteins on the virion exhibiting native multimer structure may be a good immunogen to present antibody epitopes, but it is often difficult to prepare immunogenic inactivated virions. Preparation of soluble glycoprotein multimers has been attempted, while virus-like particles carrying target glycoproteins can be a more immunogenic antigen. In the present study, a target glycoprotein-embedded Sendai virus (SeV) particle was developed for induction of anti-virus antibodies. We constructed a chimeric antigen, HIV-1 EnvF, consisting of HIV-1 Env ectodomain and SeV F transmembrane-cytoplasmic domain, which was shown to be efficiently incorporated into the SeV virion. EnvF was recognized by anti-HIV-1 broadly-neutralizing monoclonal antibodies (bnAbs) including 35O22 that targets an Env trimer-dependent epitope. Analysis revealed that HIV-1_AD8 EnvF can mediate viral entry into the cells, which is inhibited by anti-HIV-1 bnAbs and HIV-1 entry inhibitors, suggesting that the EnvF exhibits an HIV-1 Env native-like functional structure to present bnAb epitopes. Immunization of mice with replication-defective SeVs expressing HIV EnvF and non-infectious SeV particles (NVP) carrying HIV EnvF efficiently induced anti-HIV Env antibodies. HTLV-1 EnvF also showed the potential to efficiently induce anti-HTLV-1 Env antibodies. These results indicate that SeV particles carrying EnvF can be a promising vaccine platform for induction of antibodies targeting enveloped virus glycoproteins.     

Establishment of a model to assess mumps virus neurovirulence in neonatal Wistar rats

Mumps virus (MuV) is highly neurotropic and neurovirulent, hence, the neurovirulence of virus seeds used in the production of mumps vaccines must be tested. The previous neurovirulence evaluation method involves measuring the area of the cavity in the Lewis neonatal rat brain caused by MuV through paraffin sectioning and hematoxylin-eosin (HE) staining. However, the processes of paraffin sectioning and HE staining are time consuming and complicated. To solve this problem, in this study, a vibratome sectioning system was first deployed to evaluate MuV neurovirulence in the rat brain instead of paraffin sectioning and HE staining. The results showed that the vibratome sectioning method could assess the neurovirulence potential of MuV more objectively and efficiently. In addition, the effects of different MuV doses and the ages of the rats in days on this evaluation method were explored. The results indicate that MuV at no less than 10 50 % cell culture infective dose (CCID₅₀) could cause obvious cavity formation in 1-day-old rat brains. The neonatal rat model developed in this study could evaluate the neurovirulence of different MuV strains with high sensitivity and good repeatability.     

Intranasal immunization with recombinant Vaccinia virus encoding trimeric SARS-CoV-2 spike receptor-binding domain induces neutralizing antibody

Respiratory transmission of SARS-CoV-2 is considered to be the major dissemination route for COVID-19, therefore, mucosal immune responses have great importance in preventing SARS-CoV-2 from infection. In this study, we constructed a recombinant Vaccinia virus (VV) harboring trimeric receptor-binding domain (RBD) of SARS-CoV-2 spike protein (VV_-tRBD), and evaluated the immune responses towards RBD following intranasal immunization against mice and rabbits. In BALB/c mice, intranasal immunization with VV_-tRBD elicited robust humoral and cellular immune responses, with high-level of both neutralizing IgG and IgA in sera against SARS-CoV-2 psudoviruses, and a number of RBD-specific IFN-γ-secreting lymphocytes. Sera from immunized rabbits also exhibited neutralization effects. Notably, RBD-specific secretory IgA (sIgA) in both nasal washes and bronchoalveolar lavage fluids (BALs) were detectable and showed substantial neutralization activities. Collectively, a recombinant VV expressing trimeric RBD confers robust systemic immune response and mucosal neutralizing antibodies, thus warranting further exploration as a mucosal vaccine.     

电阻抗断层成像技术用于呼气末正压滴定的研究进展

适当的呼气末正压（PEEP）是保护性肺通气策略的重要组成部分,PEEP可以保持肺泡开放,减少肺萎陷伤。尽管个体化PEEP已被越来越多的临床医师认可,但最佳的PEEP滴定方法尚存争议。电阻抗断层成像（EIT）是一种无创、无辐射的成像技术,可在床边实时动态评估肺功能,将肺通气过程中的阻抗变化以动态图像呈现,能够反映PEEP调整前后肺内通气及气体分布变化,因此,EIT可用于滴定个体化PEEP。本文简要概括EIT的基本原理及监测指标,阐述临床应用EIT指导下的PEEP（PEEPEIT）滴定方法,旨在加强对EIT的优点和局限性的理解,为优化个体化PEEP的设置提供参考。     

肠道淋巴瘤与EB病毒相关性研究

目的：探讨EB病毒（Epstein-Barr virus,EBV)感染在肠道淋巴瘤发病中的意义。方法：采用EBV的DNA原位杂交及S－P法免疫组化技术（第一抗体为EBV、CD3、CD20、CD43、CD45、CD45RO、CD74等），观察24例肠道淋巴瘤患者（8例肠病相关T细胞淋巴瘤、16例黏膜相关淋巴组织B细胞淋巴瘤）EBV感染情况。以20例慢性结肠炎作为对照。结果：患者年龄21－92岁（平均52．8岁），男女之比为3．8：1。临床上均以腹痛、腹胀或便血就诊。组织病理学：T细胞淋巴瘤细胞多形性、核大，不规则，嗜血管性及大片坏死；B细胞淋巴瘤细胞中等大小，多呈圆形、椭圆形、胞质较少淡染，核稍大，核分裂象多见，可见“淋巴上皮病变”。24例淋巴瘤中检出（原位杂交及免疫组化）EBV－DNA 14例（检出率为58．3％），其中T细胞淋巴瘤EBV的检出率为75％，B细胞淋巴瘤EBV的检出率为50％（P＜0．01）。结论：肠道淋巴瘤的发生与EBV的感染有明显的相关性。     

禽流感病毒核蛋白单克隆抗体的制备及部分特性鉴定

目的：制备抗禽流感病毒（AIV）核蛋白（NP）的单克隆抗体（mAb）并进行特性鉴定。方法：分别用甲醛灭活的和TritonX-100裂解的AIV H9N2及AIVNP基因的原核表达产物免疫BALB／c小鼠。经细胞融合、间接ELISA筛选及克隆化，建立能稳定分泌抗AIV NP mAb的杂交瘤细胞株。mAb的效价采用间接ELISA测定，用交义反应试验及间接免疫荧光染色法检测mAb的特异性。结果：经细胞融合、筛选及克隆化，间接ELISA法测定，mAb共得到6株能稳定分泌抗禽流感病毒NPmAb的杂交瘤细胞株，分别命名为4F4、1C3、1G11、1C2、1D10及2E7。1G11、1D10腹水的ELISA效价最高，分别为2^-13和2^-14。交叉反应试验及间接免疫荧光染色检测表明，两株mAb的特异性良好。结论：其获得6株抗AIVNP的mAb，其中2株mAb1C11和1D10的效价最高，特异性良好，为AIV的研究及快速诊断方法的建立奠定了基础。