Comparative analyses of influenza virus receptor distribution in the human and mouse brains

Accumulating evidence suggests a potential link between influenza A virus infection and the occurrence of influenza-associated neurological disorders. As influenza infection is mediated by specific receptors on the host cell surface, it is important to understand the distribution patterns of influenza receptors in target organs. We carried out comprehensive experiments to localize influenza receptors in the brains of two different mouse strains and the human brain for comparison using lectin histochemistry. We further compared the brain regions in which influenza receptors were expressed and the regions in which experimental influenza infection was observed. Our results show that the expression patterns for influenza receptors in mouse and human brains are different. In the mouse brain, human influenza virus receptors (HuIV-R) were expressed in part of brainstem and cerebellar white matter while avian influenza virus receptors (AIV-R) were expressed in the cerebellar Purkinje neurons. In contrast, in the human brain, many neurons and glia in widespread regions, including the cerebral cortex, hippocampus, brainstem, and cerebellum, express both AIV-R and HuIV-R. Importantly, vascular endothelial cells, choroid plexus epithelial cells and ependymal cells in both mouse and human brains express high levels of HuIV-R and AIV-R. The regional reciprocity was not observed when comparing regions with influenza receptor expression and the regions of influenza infection within the mouse brain. Our results demonstrate a differential influenza receptor expression pattern in mouse and human brains, and a disparity between influenza receptor distribution and regions with actual influenza infection.     

Differences by sex in IgG levels following infant and childhood vaccinations: An individual participant data meta-analysis of vaccination studies

BackgroundIf immune responses to vaccination differ between males and females, sex-specific vaccination schedules may be indicated. We systematically reanalysed childhood vaccination studies conducted in The Netherlands for sex-differences in IgG-responses. To assess the impact of potential sex-differences in IgG-responses, we explored sex-differences in vaccine failure/effectiveness and reactogenicity.MethodsSix studies with IgG-measurements for 1577 children following infant pneumococcal (PCV7/PCV10/PCV13) and/or DTaP-IPV-Hib(-HepB) vaccinations, or the pre-school DTaP-IPV booster were included. We performed one-stage individual participant data meta-analyses per time-point of the effect of sex on IgG levels against pneumococcal serotypes, diphtheria toxoid, tetanus toxoid, pertussis Ptx/FHA/Prn and Hib-PRP using linear mixed models. Using existing study data, we compared reactogenicity after PCV7/PCV10 and DTaP-IPV-Hib(-HepB) vaccination in girls and boys. Vaccine failure/effectiveness was compared between girls and boys for invasive pneumococcal disease (IPD), invasive Hib disease and pertussis using notification data.ResultsFor pneumococcal vaccination, the geometric mean concentration ratio of IgG levels in girls versus boys pooled across serotypes was 1.15 (95%CI 0.91–1.45) 1 month following the primary series, 1.16 (1.02–1.32) at age 8 months, 1.12 (1.02–1.23) pre-booster (age 11 months) and 0.99 (0.89–1.10) post-booster (age 12 months). Diphtheria toxoid, tetanus toxoid, pertussis Ptx/FHA/Prn and Hib-PRP IgG levels did not differ between girls and boys, except for Hib post-booster (1.24; 95%CI 1.01–1.52) and tetanus before pre-school booster (0.71; 0.53–0.95). We found no difference between boys and girls in reactogenicity at age 4 or 11 months or in vaccine failure/effectiveness for IPD, invasive Hib disease or pertussis.ConclusionFor most vaccine antigens investigated, there were no consistent differences in vaccine-induced IgG levels. Vaccine-induced pneumococcal IgG levels were slightly higher in girls, but only between the primary series and the 11-month booster. These results, along with similar reactogenicity and vaccine failure/effectiveness, support the uniform infant vaccination schedule in the Dutch national immunisation programme.     

山东省艾滋病病毒感染者抗病毒治疗继发性耐药影响因素的病例对照研究

目的 了解HIV感染者抗病毒治疗发生继发性耐药的影响因素,为提高山东省抗病毒治疗效果提供依据。方法 按照病例对照研究设计,1∶2匹配病例组和对照组,2015年10月进行入户面对面调查。根据山东省级实验室自建的HIV感染者抗病毒治疗耐药数据库和艾滋病综合防治数据信息系统,筛选研究对象。样本量估计为330例（病例110例、对照组220例）,研究对象为在山东省存活的HIV感染者、年龄≥15岁、参加抗病毒治疗≥6个月并检测病毒载量（VL）。针对VL>1 000拷贝/ml者进行实验室耐药检测,筛选出继发性耐药者作为病例组,非继发性耐药者为对照组。采用EpiData 3.1软件和SPSS 22.0软件建立数据库,运用非条件逐步logistic回归分析继发性耐药的影响因素。结果 研究对象共288例（病例组103例、对照组185例）。病例组年龄为（37.62±1.06）岁,对照组年龄为（37.90±0.74）岁,以男性、已婚/同居者、高中及以下文化程度、汉族为主。多因素logistic回归分析结果显示,与治疗时间<1年相比,治疗时间1～3年和>3年的OR值分别为8.80（95% CI：3.69～21.00）、3.00（95% CI：1.20～7.53）;与未漏服相比,漏服比例>25.0%的OR值为15.41（95% CI：4.59～51.71）;本人领药OR值为0.22（95% CI：0.07～0.74）。结论 HIV感染者的治疗时间、漏服比例、本人领药为其抗病毒治疗继发性耐药的影响因素。治疗时间≥1年、漏服药物比例>25%为继发性耐药的危险因素,本人领药为继发性耐药的保护因素。应加强治疗优化的干预力度,提高HIV感染者本人对服药的认知水平。     

山东省女子强制隔离戒毒所女性吸毒者Ⅱ型单纯疱疹病毒感染及相关因素分析

目的 了解山东省女子强制隔离戒毒所（山东女子强戒所）女性吸毒者Ⅱ型单纯疱疹病毒（HSV-2）感染情况及其相关因素,为HSV-2的有效防控工作提供参考依据。方法 对山东女子强戒所全体451名女性吸毒者进行筛查,开展问卷调查并进行HSV-2、HIV和梅毒血清学检测。采用EpiData 3.1软件建立数据库,SPSS 20.0软件进行χ²检验和多因素logistic回归分析。结果 共调查女性吸毒者451人,HSV-2感染率为72.1%（325/451）,HIV感染率为2.2%（10/451）,梅毒感染率为33.5%（151/451）。单因素分析显示,知晓艾滋病知识、使用毒品后的主要性伴是临时性伴、使用毒品后曾同时与多人发生过性行为、入所前曾提供过商业性服务、入所前曾发生过临时性行为、感染梅毒与HSV-2的感染相关。多因素分析显示,与未提供商业性服务者相比,提供过商业性服务者感染HSV-2的OR值（95% CI）为2.90（1.19~7.06）;与未感染梅毒者相比,感染梅毒者感染HSV-2的OR值（95% CI）为2.75（1.63~4.63）。结论 山东省女性强戒吸毒者HSV-2感染率较高,应加强HSV-2防治措施,推广使用安全套预防性传播疾病。     

Complete genome sequence of enterovirus 87 isolated from a child with acute flaccid paralysis in China in 2000

Enterovirus 87 (EV87) is a new member of species Human Enterovirus B. So far, only the genome sequence of the prototype strain from Bangladesh is available. Here, we report the genome sequence of EV87 strain LY02/SD/CHN/2000 isolated from an acute flaccid paralysis case in Shandong Province, China, in 2000. It has a genome of 7423 nucleotides. Compared with the prototype strain, it had 80.3 % nucleotide and 95.5 % amino acid similarity in the VP1 coding region and 82.8 % complete genome similarity, reflecting distant genetic relationship between them. Phylogenetic analysis provided evidence of recombination with other serotypes in the P2 and P3 coding regions.     

乙型肝炎疫苗初次免疫正常应答和高应答婴儿初次免疫5年后免疫记忆持久性随访观察

目的 探讨乙型肝炎(乙肝)疫苗初次免疫(初免)正常应答和高应答新生儿在初免后5年免疫记忆情况及其影响因素。方法 对初免正常应答和高应答新生儿于初免后5年检测其抗-HBs,其中低于保护水平(10 mIU/ml)者接种1剂次乙肝疫苗(激发剂次)并于接种后14 d采集血标本,再次检测抗-HBs,并计算激发剂次后抗-HBs阳转率(≥10 mIU/ml)和GMT。将检测的初免抗体、随访抗体和激发剂次后抗体均从低到高分成不同等级,分析激发剂次后抗体的影响因素。结果 37.98%(980/2 580)初免正常应答和高应答新生儿在初免后5年抗-HBs已降至保护水平以下,其中激发剂次后98.95%(757/765)出现抗体阳转,GMT为2 811.69(95%CI:2 513.55～3 145.19) mIU/ml。激发剂次后抗体滴度随初免抗体水平和随访抗体水平的升高而升高(F值分别为5.46、10.23,均P<0.000 1)。多因素分析显示,激发剂次后抗体滴度与性别、出生体重、早产等无关(P>0.05),而与初免抗体和随访抗体水平独立相关(OR=1.001,95%CI:1.000～1.002,P<0.001;OR=1.28,95%CI:1.81～1.39,P<0.001)。结论 新生儿乙肝疫苗初免后5年存在较强的免疫记忆;免疫记忆的强度与初免抗体及激发剂次前抗体水平有关。     

Molecular evolution of hepatitis B vaccine escape variants in China,during 2000–2016

Hepatitis B vaccine escape variants are the main threat to hepatitis B virus (HBV) infection in vaccination era worldwide. With 215 genotype B HBV and 313 genotype C HBV vaccine escape variants isolated from China during 2000–2016, we reported that genotype B HBV vaccine escape strains diverged in ∼1997 (95% HPD; 1987–2005), while genotype C HBV vaccine escape strains diverged in ∼1976 (95% HPD; 1955–2003). Additionally, the p-distance of genotype C HBV vaccine escape strains was 0.0291 ± 0.0169, which was significantly higher than that in the genotype B HBV (t = 131.02, p < 0.05). However, genotype B HBV vaccine escape strains evolved more rapidly than genotype C HBV (2.103 × 10⁻³ vs 1.083 × 10⁻³ substitutions/site/year). Bayesian skyline plot analysis showed that the populations of genotype C HBV vaccine escape strains fluctuated more than those in genotype B HBV. Four sites (A5T/S, L21S, T/A126S and T/N131I/A) and 13 sites (N3S, T5A, G10Q/R/E, L21S, T47K/A/V, L98V/P, I/S126N/V/T, Q129H/R/L, T131P/I/N/A, G145A/R, L175S/F, L213I/S, V224A/G) were found to be under positive selection in genotype B and C HBV vaccine escape strains, respectively. More importantly, N3S, L21S, T47K, L98V, I/S126T and L213I mutations were detected in 1 (2.5%), 1 (2.5%), 1 (2.5%), 3 (7.5%), 1 (2.5%), 1 (2.5%) genotype C HBV infected Chinese younger with neonatal HBV vaccination, respectively. Therefore, our results should be valuable in further understanding the molecular evolution of HBV and providing new ideas for the elimination of HBV infection.     

Expression and function of miRNA in postoperative radiotherapy sensitive and resistant patients of non-small cell lung cancer

Purpose

To investigate the different miRNA expression profiles of postoperative radiotherapy sensitive and resistant patients of non-small cell lung cancer, explore their potential role and find some radio-sensitivity markers.

Materials and methods

Thirty non-small cell lung cancer patients who have been treated by postoperative radiotherapy were selected and were divided into radiotherapy sensitive group and resistant group according to overall survival and local or distant recurrence rate. Expression profile of miRNA in these two groups was detected by a microarray assay and the results were validated by quantitative RT-PCR and Northern blot. At the molecular level, the effect of one differently expressed miRNA (miR-126) on the growth and apoptosis of SK-MES-1 cells induced by irradiation was examined.

Results

Comparing with resistant patients, five miRNAs (miRNA-126, miRNA-let-7a, miRNA-495, miRNA-451 and miRNA-128b) were significantly upregulated and seven miRNAs (miRNA-130a, miRNA-106b, miRNA-19b, miRNA-22, miRNA-15b, miRNA-17-5p and miRNA-21) were greatly downregulated in radiotherapy sensitive group. Overexpression of miRNA-126 inhibited the growth of SK-MES-1 cells and promoted its apoptosis induced by irradiation. The expression level of p-Akt decreased in miRNA-126 overexpression group. After treating with phosphoinositidyl-3 kinase (PI3K) constitutively activator (IGF-1) and inhibitor (LY294002), miRNA-126 overexpression had no significant effects on the apoptosis of SK-MES-1 cells.

Conclusion

We found 12 differently expressed miRNAs in the radiotherapy sensitive and resistant non-small cell lung cancer samples. Moreover, our results showed miRNA-126 promoted non-small cell lung cancer cells apoptosis induced by irradiation through the PI3K-Akt pathway.