高渗盐水和甘露醇在动脉瘤性蛛网膜下腔出血患者降低颅内压中的应用

目的比较3%高渗盐水和20%甘露醇治疗重症动脉瘤性蛛网膜下腔出血所致颅内压增高的疗效.方法25例动脉瘤性蛛网膜下腔出血患者出现颅内压增高事件时, 随机交替接受等渗透剂量的160 mL 3%高渗盐水与150 mL 20%甘露醇进行降低颅内压治疗, 连续监测患者颅内压、平均动脉压、脑灌注压及中心静脉压.记录有效降低颅内压持续时间、颅内压最大降幅及其时间, 用药前及用药后1 h、3 h血钠水平及血浆渗透压.结果3%高渗盐水和20%甘露醇均可降低颅内压(均 P < 0.01), 两者的降低颅内压作用持续时间及颅内压降幅差异均无统计学意义(均 P >0.05).患者脑灌注压较用药前均上升(均 P < 0.01), 平均动脉压先上升后下降, 但差异无统计学意义( P >0.05).患者中心静脉压稍有波动, 但差异均无统计学意义(均 P >0.05).20%甘露醇治疗后患者血钠下降, 3%高渗盐水治疗后患者血钠值上升, 变化均有统计学意义(均 P < 0.05).20%甘露醇及3%高渗盐水治疗后患者血浆渗透压均先上升后下降, 变化均有统计学意义(均 P < 0.01). 结论3%高渗盐水可作为治疗动脉瘤性蛛网膜下腔出血所致颅内压增高患者的一线治疗药物.     

《艾滋病诊疗指南第三版(2015版)》更新解读

2015年中华医学会感染病学分会艾滋病学组发布了第三版《艾滋病诊疗指南》。新版指南强调抗病毒治疗时点前移:一旦成人确诊感染人类免疫缺陷病毒(HIV), 若无禁忌宜尽早启动抗HIV治疗。对于合并机会性感染的HIV感染者, 在感染控制、病情稳定后也应及早开始抗病毒治疗。尤其强调HIV合并结核患者在CD4阳性淋巴细胞数少于200/μL的情况下, 建议抗结核两周内即开始抗病毒治疗。在抗HIV治疗用药中, 淘汰了一些毒副作用大、依从性较差的药物, 如司他夫定、去羟肌苷、茚地那韦等, 优选抗病毒效力强、服药方便的组合, 如拉米夫定、替诺福韦、依非韦伦组合。对于HIV感染的婴幼儿, 亦主张及早抗HIV治疗。对于五岁以内的幼儿, 主张确诊后即启动抗病毒治疗。对于HIV感染的孕产妇, 建议尽快予以全程、联合抗HIV治疗, 寓防于治。     

维生素B12和叶酸干预对绝经后骨质疏松症妇女的骨代谢及同型半胱氨酸水平的影响

目的观察叶酸和维生素B12对绝经后骨质疏松症妇女的骨代谢及同型半胱氨酸水平的影响。方法 80例绝经后骨质疏松症妇女参加研究。所有参与者随机接受叶酸和维生素B12(n=40)或安慰剂(n=40)治疗。在干预前的基线及干预后3个月和6个月,测量两组患者血清同型半胱氨酸、维生素B12和骨代谢标志物的水平。结果治疗前,两组患者血清同型半胱氨酸、维生素B12和骨代谢标志物水平比较差异无统计学意义(P0.05)。治疗后,两组患者同型半胱氨酸均下降,但比较差异无统计学意义(P0.05)。6个月后各组间血清维生素B12、骨钙素、CTX的变化均有显著改变且差异有统计学意义(P0.05)。结论绝经后骨质疏松症妇女补充叶酸和维生素B12可以一定程度改善同型半胱氨酸及骨代谢指标水平。     

艾滋病儿童神经认知障碍相关因素研究进展

目的 总结艾滋病儿童神经认知障碍影响因素。方法 在PubMed、Web of Science、CNKI、万方和维普数据库，以“艾滋病”、“儿童”、“神经认知障碍”、“脑病”、“影响因素”为主题词或关键词，同时辅以手工检索和文献追溯检索近年相关文献。着重整理影响艾滋病儿童神经认知障碍的因素。对资料进行汇总并撰写综述。结果 检索并阅读相关文献100余篇。艾滋病病毒相关因素（HIV损害中枢神经系统、HIV逃逸及病毒储存库、HIV亚型）、宿主因素（启动抗病毒治疗时机、遗传因素、营养状况及合并其他疾病）、抗病毒治疗药物、社会心理因素等均可影响艾滋病感染儿童神经认知。结论 为了尽可能避免或降低艾滋病儿童神经认知障碍，应当尽早诊断、尽早给予高效的抗逆转录病毒治疗；随访中应重视神经认知发育的观察和筛查，及早识别神经认知障碍，积极寻找多方面的原因并进行有效干预。     

The Health Belief Model in predicting healthcare workers' intention for influenza vaccine uptake in Jordan

BackgroundTheories of health behavior change are being inadequately adopted to understand the reasons behind low influenza vaccination rates among healthcare workers (HCWs). The Theory of Planned Behavior (TPB) is being used to predict intention-behavior relationship while the Health Belief Model (HBM) is being employed to predict actual behavior. The purpose of this study was to test a conceptual model based on the HBM’s constructs to predict Jordanian HCWs’ intentions for influenza vaccine uptake as an alternative to the TPB.MethodA cross-sectional questionnaire-based study was conducted in 2016 in a tertiary teaching hospital in Amman-Jordan including a convenience sample of 477 HCWs with direct patient contact. The study instrument was tested for validity and reliability. A conceptual regression model was proposed incorporating the constructs of the primary HBM with some modifications in the threat construct as well as an additional variable about explicit past vaccination behavior (in the past year and/or any previous history of influenza vaccine uptake).ResultsAlmost all the constructs of the HBM demonstrated significant differences between participants intending and those who did not intend to vaccinate against influenza. After adjusting for the confounding variables in the final conceptual regression model, past vaccination behavior (OR= 4.50, 95%Confidence Interval 3.38–6.00, P< 0.0005) and the perceived benefit scale (OR= 1.19, 95% Confidence Interval 1.11–1.28, P< 0.0005) were the only significant predictors of intentions to vaccinate against influenza in the next season.ConclusionTaking into consideration the altruistic beliefs of HCWs and their explicit past vaccination history augments the utility of the original HBM tool in predicting HCWs’ intentions to vaccinate against influenza in a way that is consistent with the predictive ability of the Theory of Planned Behavior.     

The respiratory syncytial virus fusion protein-specific B cell receptor repertoire reshaped by post-fusion subunit vaccination

Respiratory syncytial virus (RSV) is the major cause of acute lower respiratory illness in children of less than 5 years of age which usually results in hospitalization or even in death. Vaccine development is hampered in consequence of a failed vaccine trial with fatalities in the 1960s. Even though research has been more focused on the RSV fusion protein in its pre-fusion conformation, maternal vaccination with post-fusion protein (post F) was considered as a promising vaccine strategy for passive immunization of babies, because post F preserves very potent neutralizing epitopes. We extensively analyzed post F-binding B cell receptor (BCR) repertoires of three vaccinees who received a post F-subunit vaccine in the context of a first-in-human, Phase 1, randomized, observer-blind, placebo-controlled clinical trial (ClinicalTrials.gov Identifier: NCT02298179). In order to compare the vaccine-induced BCR repertoires with BCR repertoires induced by natural infection, we also analyzed pre F- and post F-binding BCRs isolated from a healthy blood donor with relatively high F-binding memory B cell (MBC) frequencies. Analysis of the vaccine-induced repertoires revealed that preferentially V_H4-encoded BCRs were expanded in response to vaccination. Estimation of antigen-driven selection further demonstrated that expanded BCRs accumulated positively selected replacement mutations which substantiated the hypothesis that post F-vaccination induces diversification of V_H4-encoded BCRs in germinal centers. Comparison of the vaccine-induced BCR repertoires with clonally related pre and post F-binding BCRs of the healthy blood donor suggested that the vaccine expanded pre/post F cross-reactive MBCs. Interestingly, several vaccine-induced BCRs shared stereotypic VDJ gene junctions with known neutralizing Abs. Once expressed for functional characterization, the selected monoclonal Abs demonstrated the predicted neutralization activities in plaque reduction neutralization assays indicating that the post F-vaccine induced expansion of neutralizing BCRs.     

Molecular simplification of lipid A structure: TLR4-modulating cationic and anionic amphiphiles

A growing body of data suggests that therapies based on Toll-like receptors (TLR) targeting, in particular TLR4, holds promise in curing autoimmune and inflammatory pathologies still lacking specific treatment, included several rare diseases. While TLR4 activators (agonists) have already found successful clinical application as vaccine adjuvants, the use of TLR4 blockers (antagonists) as antisepsis agents or as agents against inflammatory diseases (including arthritis, multiple sclerosis, neuroinflammations) and cancer is still at a preclinical phase of development. This minireview focuses on recent achievements on the development of TLR4 modulators based on lipid A structure simplification, in particular on compounds having disaccharide or monosaccharide structures. As the TLR4 activity of natural TLR4 ligands (lipopolysaccharide, LPS and its biologically active part, the lipid A) depends on both the structure of endotoxin aggregates in solution and on single-molecule interaction with MD-2 and CD14 receptors, the rational design of TLR4 modulators should in principle take into account both these factors. In the light of the most recent advances in the field, in this minireview we discuss the structure–activity relationship in simplified lipid A analogs, with cationic or anionic amphiphilic structures.     

TLR9在不同胎龄新生儿脐血中的表达变化

目的 通过观察早产儿不同胎龄Toll样受体9（TLR9）的表达，探讨早产儿免疫功能低下的机制。方法 采集2010年7月至2014年6月在上海市嘉定区妇幼保健院产科出生的活产新生儿的脐血229份，按胎龄分为4组，28~31周组，31~34周组，34~37周组，≥37周组，采用流式细胞术和实时荧光定量PCR方法，分别检测其TLR9的蛋白和mRNA表达情况，了解其与胎龄之间的关系，并分析mRNA和蛋白表达间的相关性。结果 TLR9阳性细胞率在28~31周组，31~34周组，34~37周组，≥37周组分别为（15.93±6.23）%，（11.63±6.70）%，（13.66±6.88）%，（20.51±12.06）%；其在胎龄28~31周较高，至31~34周逐渐下降至最低，两组差异有统计学意义（P<0.05）；34~37周后TLR9阳性细胞率表达逐渐升高，至≥37周达最高，两胎龄组比较，差异具有统计学意义（P<0.05）。31~37周间新生儿脐血TLR9阳性细胞率与胎龄呈正相关（r=0.273，P=0.006）。TLR9 mRNA表达在28~31周组，31~34周组，34~37周组，≥37周组分别为（4.95±3.44）%，（8.89±8.49）%，（13.91±10.92）%，（7.19±7.11）%；其在28~36周逐渐升高，与胎龄呈正相关（r=0.355，P< 0.001）。≥37周TLR9 mRNA表达量下降，该值虽高于28~31周，但差异无统计学意义（P>0.05）。相关性分析表明，同胎龄时期同样本新生儿的TLR9 mRNA和TLR9阳性细胞率之间存在负相关（r=-0.227，P=0.011）。结论 TLR9阳性细胞率和TLR9 mRNA表达在不同胎龄组新生儿间有差异，TLR9阳性细胞率表达在31~37周间随着胎龄的增加而增加，TLR9 mRNA在28~36周间随着胎龄的增加而增加。