Inactivated influenza vaccine formulated with single-stranded RNA-based adjuvant confers mucosal immunity and cross-protection against influenza virus infection

Influenza vaccination is considered the most valuable means to prevent and control seasonal influenza infections, which causes various clinical symptoms, ranging from mild cough and fever to even death. Among various influenza vaccine types, the inactivated subunit type is known to provide improved safety with reduced reactogenicity. However, there are some drawbacks associated with inactivated subunit type vaccines, with the main ones being its low immunogenicity and the induction of Th2-biased immune responses. In this study, we investigated the role of a single-stranded RNA (ssRNA) derived from the intergenic region in the internal ribosome entry site of the Cricket paralysis virus as an adjuvant rather than the universal vaccine for a seasonal inactivated subunit influenza vaccine. The ssRNA adjuvant stimulated not only well-balanced cellular (indicated by IgG2a, IFN-γ, IL-2, and TNF-α) and humoral (indicated by IgG1 and IL-4) immune responses but also a mucosal immune response (indicated by IgA), a key protector against respiratory virus infections. It also increases the HI titer, the surrogate marker of influenza vaccine efficacy. Furthermore, ssRNA adjuvant confers cross-protective immune responses against heterologous influenza virus infection while promoting enhanced viral clearance. Moreover, ssRNA adjuvant increases the number of memory CD4⁺ and CD8⁺ T cells, which can be expected to induce long-term immune responses. Therefore, this ssRNA-adjuvanted seasonal inactivated subunit influenza vaccine might be the best influenza vaccine generating robust humoral and cellular immune responses and conferring cross-protective and long-term immunity.     

The differential roles of contralesional frontoparietal areas in cortical reorganization after stroke

BackgroundStudies examining the contribution of contralesional brain regions to motor recovery after stroke have revealed conflicting results comprising both supporting and disturbing influences. Especially the relevance of contralesional brain regions beyond primary motor cortex (M1) has rarely been studied, particularly concerning the temporal dynamics post-stroke.MethodsWe, therefore, used online transcranial magnetic stimulation (TMS) interference to longitudinally assess the role of contralesional (right) frontoparietal areas for recovery of hand motor function after left hemispheric stroke: contralesional M1, contralesional dorsal premotor cortex (dPMC), and contralesional anterior intraparietal sulcus (IPS). Fourteen stroke patients and sixteen age-matched healthy subjects performed motor tasks of varying complexity with their (paretic) right hand. Motor performance was quantified using three-dimensional kinematic data. All patients were assessed twice, (i) in the first week, and (ii) after more than three months post-stroke.ResultsWhile we did not observe a significant effect of TMS interference on movement kinematics following the stimulation of contralesional M1 and dPMC in the first week post-stroke, we found improvements of motor performance upon interference with contralesional IPS across motor tasks early after stroke, an effect that persisted into the later phase. By contrast, for dPMC, TMS-induced deterioration of motor performance was only evident three months post-stroke, suggesting that a supportive role of contralesional premotor cortex might evolve with reorganization.ConclusionWe here highlight time-sensitive and region-specific effects of contralesional frontoparietal areas after left hemisphere stroke, which may influence on neuromodulation regimes aiming at supporting recovery of motor function post-stroke.     

Prevalence and correlates of mild cognitive impairment among diverse Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging results

IntroductionWe estimated the prevalence and correlates of mild cognitive impairment (MCI) among middle-aged and older diverse Hispanics/Latinos.MethodsMiddle-aged and older diverse Hispanics/Latinos enrolled (n = 6377; 50–86 years) in this multisite prospective cohort study were evaluated for MCI using the National Institute on Aging–Alzheimer's Association diagnostic criteria.ResultsThe overall MCI prevalence was 9.8%, which varied between Hispanic/Latino groups. Older age, high cardiovascular disease (CVD) risk, and elevated depressive symptoms were significant correlates of MCI prevalence. Apolipoprotein E4 (APOE) and APOE2 were not significantly associated with MCI.DiscussionMCI prevalence varied among Hispanic/Latino backgrounds, but not as widely as reported in the previous studies. CVD risk and depressive symptoms were associated with increased MCI, whereas APOE4 was not, suggesting alternative etiologies for MCI among diverse Hispanics/Latinos. Our findings suggest that mitigating CVD risk factors may offer important pathways to understanding and reducing MCI and possibly dementia among diverse Hispanics/Latinos.     

糖尿病肾病内热证与肾功能及炎症因子的相关性研究

目的:观察糖尿病肾病不同分期内热证与肾功能及炎症指标的相关性。方法:收集202例糖尿病肾病患者的临床资料,采用酶联免疫吸附法检测微炎症指标,包括超敏C反应蛋白(high-sensitivity C-reactive protein,HS-CRP)、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α),进行统计分析。结果:与非内热证组比较,中期、晚期内热证组24小时尿蛋白定量明显升高;晚期内热证组的血清肌酐明显升高,肾小球滤过率(glomerular filtration rate,GFR)明显降低;炎症因子CRP、IL-6、TNF-α随疾病进展均呈上升趋势;晚期内热证组与非内热证组比较,IL-6、TNF-α升高;中期HS-CRP与内热积分呈正相关,晚期TNF-α与内热积分呈正相关。结论:内热病机贯穿于糖尿病肾病的始终,与糖尿病肾病肾功能以及疾病进展密切相关;同时,内热积分与炎症因子HS-CRP、TNF-α的表达存在一定的相关性,这种相关性在疾病中期、晚期表现更加明显。     

重症心源性肺水肿伴休克患者的机械通气治疗

目的研究重症心源性肺水肿伴休克患者机械通气(MV)治疗时通气压力的选择对预后的影响。方法将符合标准的22例患者分为两组对照组9例,常规给予较低通气压力和加强药物治疗;治疗组13例,适当增加通气压力。观察血压、临床症状和动脉血气的变化。结果调整MV后30分钟时,治疗组收缩压迅速由(95±12)mmHg升至(130±15)mmHg(P<0.001),呼吸频率(RR)由(38±11)次/min降至(27±6)次/min(P<0.005),心率(HR)由(126±15)次/min降至(105±12)次/min(P<0.001);对照组上述指标变化不明显。2小时后治疗组的升压药用量减少(70±15)%,对照组则增加(20±5)%;同时在吸氧浓度不变的情况下,治疗组的PaO2由(81±12)mmHg升至(140±15)mmHg(P<0.001),明显高于对照组PaO2的改善。24~48小时内治疗组11例患者(85%)停用升压药,对照组2例(22%)停用。最终治疗组100%的患者好转出院,对照组为45%(P<0.05)。结论与低压力通气相比,适当增加MV通气压力不仅可迅速改善重症心源性水肺肿伴休克患者的低氧血症,也可迅速升高血压,改善心功能,降低病死率。     

组织多普勒成像评价左房收缩功能的临床研究

目的应用多普勒组织成像技术测定61名健康成人二尖瓣环运动峰值速率(Am),以评价Am在左房收缩功能中的价值。方法观察61名无心脏疾患者的Am,Am值为二尖瓣前、后、左、右侧心房收缩期二尖瓣环运动峰值速率的平均值;并与左房收缩时左房面积改变分数(FAC)和容积改变分数(FVC)作相关性研究。结果61例研究对象平均FAC和FVC分别为(31±10)%和(42±11)%;Am为(13.4±3.2)cm/s;直线回归分析显示,Am与FAC和FVC均呈正相关(r=0.78和0.82;P均<0.001)。结论Am与FAC、FVC具有良好相关性,从而为临床评价左房收缩功能提供了一种简便而快速的方法。     

他汀类药物对肝功能影响的研究

目的观察他汀类药物对肝功能的影响,探讨定期检测肝功能的必要性。方法选择2004年9月至2005年3月门诊就诊心血管病患者,了解其所用他汀类药物的种类和剂量,每月复查血脂水平和肝功能。结果所用他汀类药物有辛伐他汀、普伐他汀、洛伐他汀和阿托伐他汀,常用剂量为10～20mg/d,治疗后总胆固醇和低密度脂蛋白胆固醇显著降低,而肝酶在治疗前、后无显著变化,肝酶升高3倍以上者所占比例低。结论他汀类药物在低剂量应用时对肝脏损伤小,没有必要频繁监测肝功能。     

Influence of SNPs in cytokine-related genes on the severity of food allergy and atopic eczema in children

Although many single nucleotide polymorphism (SNP) studies have reported an association of atopy, allergic diseases and total serum immunoglobulin E (IgE) levels, almost all of these studies sought risk factors for the onset of these allergic diseases. Furthermore, many studies have analyzed a single gene and hardly any have analyzed environmental factors. In these analyses, the results could be masked and the effects of other genes and environmental factors may be decreased. Here, we described the correlation between four genes [interleukin (IL)-4 (C-590T), IL-4 receptor (A1652G), FCER1B (G6842A) and STAT6 (G2964A)] in connection with IgE production; the role of IL-10 (C-627A) as a regulatory cytokine of allergy; and the severity of food allergy (FA) and atopic eczema (AE) in 220 Japanese allergic children. In addition to these SNPs, environmental factors, i.e., patient's attitude, indoor environment, and so on, were also investigated in this study. Our study was retrospective, and the correlation was analyzed by our defined clinical scores divided into three terms: worst symptoms, recent symptoms and general amelioration at the most recent examination during the disease course. Our results indicated that IL-10 AA, the genotype with lower IL-10 production, is associated with higher IgE levels in the serum (p < 0.0001, estimate; 0.912). Marginal liver abnormalities were observed in the subject group with both FA and AE (p < 0.1191, estimate; 0.1490). Our defined clinical scores enabled evaluation of various aspects of disease severity. Based on the scores, while no single SNP selected in this study determined severity, the combination of the SNP with laboratory data and environmental factors appeared to determine severity.     

多巴胺或多巴胺复合去甲肾上腺素对肝移植术中患者血液动力学、氧代谢及肾功能的影响

目的评价原位肝脏移植术(OLT)中持续输注多巴胺或多巴胺复合去甲肾上腺素对血液动力学、组织氧代谢和肾功能的影响。方法拟行OLT的患者30例,ASAⅢ或Ⅳ级,随机分为2组 (n=15)。A组:术中持续输注多巴胺,初始输注速率为1-3μg·kg-1·min-1;B组:术中持续输注多巴胺复合去甲肾上腺素,初始输注速率分别为1-3μg·kg-1·min-1和0．03μg·kg-1·min-1,多巴胺输注速率不超过5μg·kg-1·min-1;术中两组均调节输注速率维持MAP 60-80 mm Hg。分别于切皮前即刻、切肝期1 h、无肝期1 h、新肝期1h和术毕测定血液动力学、组织代谢和肾功能指标。结果两组HR、 MAP均维持较平稳。无肝期两组CVP、MPAP、PAWP、CO、CI、DO2、VO2降低(P<0．05);SVR和SVRI升高(P<0．05),但均在正常范围内。术中PVR、PVRI、pH及SvO2均较平稳。乳酸浓度增高并持续到术毕。两组术中Cr和BUN均在正常范围,B组总尿量高于A组(P相似文献