新兵训练后功能性闭经女兵的心身症状与激素水平

目的:探讨新人伍女兵功能性下丘脑性闭经(FHA)者与月经正常者激素水平及心理健康状况的差异。方法:在某部队新人伍女兵98人接受了为期近4个月的体能训练之后,有54人出现闭经.其中闭经3个月以上者有35人(研究组)。训练后月经正常、在采血时月经周期处于第5～11天者有26人(对照组)。分别测定她们血清中的促卵泡生成素(FSH)、黄体生成素(LH)、雌二醇(E_2)、孕酮(P)、泌乳素(PRL)、睾酮(T)、ACTH、T_3、T_4的水平,并用SCL-90分别评定她们的心理健康状况。结果:FHA 者血清FSH 值为4.96±1.73 mIU/ml,LH 值为2.63±1.78 mIU/ml,E_2的值为7.23±5.37 pg/ml,对照组血清相应值为10.73±2.30mIU/ml、12.31±2.15mIU/ml、41.67±6.13pg/ml,差异有统计学意义(P<0.01),闭经组低于对照组。FHA 组SCL-90的躯体化、人际敏感、抑郁、焦虑及其他因子分大于2的比率分别为:51.4%、42.9%、48.6%、51.4%及37.1%;而对照组这5项分值大于2的比率分别为15.4%、15.4%、19.2%、21.3%及11.5%,两组间这5个因子大于2的人数差异有统计学显著意义(P<0.05),闭经组高于对照组。结论:诊断为FHA 的女兵与月经正常女兵的激素水平有差异,闭经组心身症状的发生率也高于对照组。     

Acellular Bordetella pertussis vaccine enhances mucosal interleukin-10 production, induces apoptosis of activated Th1 cells and attenuates colitis in Galphai2-deficient mice

Mice deficient for the inhibitory G protein subunit alpha2 (Galphai2(-/-)) spontaneously develop a progressive inflammatory bowel disease resembling ulcerative colitis, and have a T helper 1 (Th1)-dominated immune response prior to onset of colitis, which is further augmented after the onset of disease. The present study was performed to investigate whether the Galphai2(-/-) mice were able to down-regulate the Th1-dominated inflammatory mucosal immune response and/or induce an anti-inflammatory Th2/T regulatory response and thereby diminish the severity of colitis following treatment with acellular Bordetella pertussis vaccine. The acellular vaccine against B. pertussis, the causative agent of whooping cough, has been demonstrated to induce a Th2-mediated response in both man and mice. We therefore treated Galphai2(-/-) mice intraperitoneally with a three-component acellular B. pertussis vaccine. The treated Galphai2(-/-) mice showed significantly increased interleukin (IL)-10 production in intestinal tissue, associated with significantly reduced colitis and decreased mortality, compared to untreated Galphai2(-/-) mice. The attenuation of colitis in Galphai2(-/-) mice was due, at least partly, to the B. pertussis surface antigen filamentous haemagglutinin (FHA), which almost completely inhibited proliferation of CD4(+) T cells and stimulated apoptosis of activated CD4(+) T helper 1 cells. In conclusion, the three-component acellular B. pertussis vaccine containing filamentous haemagglutinin increases the production of IL-10 in the intestinal mucosa, induces apoptosis of activated Th1 cells and attenuates colitis in Galphai2(-/-) mice.     

Antibody persistence and safety and immunogenicity of a second booster dose nine years after a first booster vaccination with a reduced antigen diphtheria-tetanus-acellular pertussis vaccine (Tdap) in adults

BackgroundOver the last decades, pertussis showed periodic increases in its incidence among adults, despite being a vaccine-preventable disease.MethodsThis phase III, multicenter, extension study (NCT00489970) was conducted in adults from the United States, followed at Year (Y) 5 and Y9 post-vaccination with a dose of reduced-antigen-content tetanus-diphtheria-acellular pertussis vaccine containing either 3 (Tdap-B group) or 5 pertussis components (Tdap-A group). Willing participants in Tdap groups and newly-recruited participants (Control group) received one Tdap-B dose at Y9. Antibody persistence (at Y5 and Y9) and safety of Tdap-B at Y9 were assessed. Non-inferiority of immune response elicited by 2 Tdap doses was evaluated at Y9: (i) versus one Tdap-B dose for diphtheria and tetanus in terms of seroprotection rates; (ii) for all antigens in terms of booster response rates (Tdap-B and Tdap-A groups versus Control group); and (iii) for pertussis antigens in terms of geometric mean concentrations (GMCs) versus a 3-dose series of a combined diphtheria-tetanus-acellular pertussis vaccine (DTPa) administered during infancy.Results1257 participants were enrolled at Y5 and 809 participants were vaccinated at Y9. Seroprotection rates in both Tdap groups were ≥98.4% and ≥98.0% (Y5) and ≥98.3% and ≥98.1% (Y9) for diphtheria and tetanus, respectively. For pertussis antigens, antibody concentrations above assay cut-offs were observed for ≥76.6% (Y5) and ≥84.9% (Y9) of participants in Tdap groups. At Y9, one month post-Tdap vaccination, comparable seroprotection/seropositivity rates and antibody GMCs were observed among groups. Non-inferiority of immune responses in both Tdap groups was demonstrated when compared to the Control group for diphtheria and tetanus and to a 3-dose DTPa series for pertussis antigens. Non-inferiority criteria in terms of booster response were not met for all antigens. No safety concerns were raised.ConclusionA second dose of Tdap-B administered in adults, 9 years after initial Tdap vaccination, is immunogenic and well-tolerated.     

Increasing FIM2/3 antigen-content improves efficacy of Bordetella pertussis vaccines in mice in vivo without altering vaccine-induced human reactogenicity biomarkers in vitro

Current acellular-pertussis (aP) vaccines appear inadequate for long-term pertussis control because of short-lived efficacy and the increasing prevalence of pertactin-negative isolates which may negatively impact vaccine efficacy. In this study, we added fimbriae (FIM)2 and FIM3 protein to licensed 2-, 3- or 5-component aP vaccines (Pentavac®, Boostrix®, Adacel®, respectively) to assess whether an aP vaccine with enhanced FIM content demonstrates enhanced efficacy. Vaccine-induced protection was assessed in an intranasal mouse challenge model. In addition, potential reactogenicity was measured by biomarkers in a human whole blood assay (WBA) in vitro and benchmarked the responses against licensed whole cell pertussis (wP) and aP vaccines including Easyfive®, Pentavac® and Pentacel®. The results show that commercial vaccines demonstrated reduced efficacy against pertactin-negative versus pertactin-positive strains. However, addition of higher amounts of FIM2/3 to aP vaccines reduced lung colonization and increased vaccine efficacy against a pertactin-negative strain in a dose-dependent manner. Improvements in efficacy were similar for FIM2 and FIM3-expressing strains. Increasing the amount of FIM2/3 proteins in aP formulations did not alter vaccine-induced biomarkers of potential reactogenicity including prostaglandin E₂, cytokines and chemokines in human newborn cord and adult peripheral blood tested in vitro. These results suggest that increasing the quantity of FIM proteins in current pertussis vaccine formulations may further enhance vaccine efficacy against B. pertussis infection without increasing the reactogenicity of the vaccine.     

An investigational tetravalent meningococcal serogroups A, C, W-135 and Y-tetanus toxoid conjugate vaccine co-administered with Infanrix™ hexa is immunogenic, with an acceptable safety profile in 12-23-month-old children

Tetravalent meningococcal serogroups ACWY conjugate vaccines will provide an advantage to those at most risk of invasive meningococcal disease; namely young children. Co-administration of ACWY-TT with DTaP-HBV-IPV/Hib was assessed in a randomized trial in 793 children aged 12-23 months. Pre-specified criteria for non-inferiority of immunogenicity following co-administration versus separate ACWY-TT and DTaP-HBV-IPV/Hib administration were reached. One month post-vaccination, ≥97.3% of ACWY-TT vaccinees had rSBA titres ≥1:8 (all serogroups). Seroprotection/seropositivity rates against DTaP-HBV-IPV/Hib antigens were ≥98.2%. The safety profile of co-administration was similar to that of DTaP-HBV-IPV/Hib alone. ACWY-TT and DTaP-HBV-IPV/Hib co-administration during the second year would facilitate introduction of ACWY-TT into routine toddler vaccination schedules.     

子宫内膜癌抑癌基因研究进展

子宫内膜癌是妇女常见的恶性肿瘤之一,发病率有逐年上升的趋势。随着分子生物学和免疫学的发展,关于子宫内膜癌分子水平的致癌机制研究日益深入,如癌基因、抑癌基因、DNA错配修复基因、雌激素代谢酶相关基因、甾体激素受体基因和细胞周期调控蛋白等。综述目前研究热点——抑癌基因的进展,为进一步探讨子宫内膜癌的发生发展、临床治疗及预后的判断提供重要依据。     

宫颈癌组织中Skp2和有丝分裂前期检查点蛋白的表达

目的:探讨宫颈癌组织中S期激酶相关蛋白2(Skp2)及有丝分裂前期检查点(Chfr)蛋白的表达及其与宫颈癌临床病理特征的关系.方法:采用免疫组织化学SP法检测60例宫颈癌组织、30例宫颈上皮内瘤变(CIN)组织及30例正常宫颈组织中Skp2和Chfr蛋白的表达.结果:宫颈癌、CIN 和正常宫颈组织中Skp2的阳性表达率分别为63.3%、30.0%和6.7%,而Chfr的阳性表达率分别为48.3%、73.3%和90.0%,组间差异均有统计学意义(χ2=28.525和16.484,P<0.001).Skp2和Chfr蛋白的表达与宫颈癌的分化程度(χ2=14.713和20.356,P<0.001)及淋巴结转移(χ2= 6.854和8.477,P=0.009和0.004)有关,而与肿瘤大小、临床分期无关.宫颈癌组织中Skp2与Chfr蛋白的表达呈负关联(rP=0.501,P<0.001).结论:Skp2和Chfr蛋白的表达与宫颈癌的发生发展有密切的关系.     

人G补缀FHA域血管生成因子1在宫颈癌组织中的表达及其临床意义

 探索人G补缀FHA域血管生成因子1（AGGF1）在宫颈癌中的表达及与宫颈癌患者预后的相关性。方法  对60例宫颈癌组织及癌旁组织进行AGGF1免疫组织化学法检测，并对其表达及与患者预后的相关性进行分析。结果  AGGF1在宫颈癌组织中的表达比癌旁组织高（P <0.05），Kaplan-meier曲线分析发现，AGGF1表达高的患者生存较差（P =0.004）。Cox回归模型分析发现，AGGF1可以作为独立指标预测宫颈癌患者术后生存。结论  宫颈癌患者AGGF1高表达预示预后较差，并且其可以作为一个独立因素来预测宫颈癌患者术后生存。

     

Vaccines for Health Care Personnel

Medical Center Occupational Health (MCOH) programs must protect health care personnel (HCP) against the occupational risk of vaccine-preventable diseases. This thematic review outlines the rationale for the use of recommended vaccines in HCP; summarizes the available evidence regarding vaccine effectiveness, administration, and assessment of immunity; and provides guidance for MCOH programs navigating challenging situations.