脑型疟疾38例临床分析

脑型疟疾为严重疾患,93%是由恶性疟疾引起[1].以来势凶、进展快、变化快,病程短为特点.如不及时抢救可意识障碍、昏迷、偏瘫、肾功能衰竭、呼吸循环衰竭而死亡.笔者于2003年7-10月在非洲马里共和国锡加索医院诊治38例成人脑型疟疾,现报告如下.     

恶性疟原虫引起的脑型疟疾1例

<正>恶性疟疾是一种凶险型疟疾,发病猛,进展快,病死率高。全世界每年发病达3亿～5亿,死亡人数达百万,但在江淮地区是很难见到的,2010年1月我院收住恶性疟原虫引起的脑型疟疾1例。1病例资料患者男,44岁。半月前在非洲工作时出现畏     

9578例新生儿卡介苗接种后12周阳转率调查

[目的]探讨本市区近5年新生儿卡介苗(BCG)接种工作的质量情况和BCG补种对提高免疫效果的实际价值。[方法]新生儿卡介苗接种后12周,用结核菌素(PPD)皮试,72h后记录皮试反应结果和卡痕大小,阴性者补种BCG。[结果]统计分析9578例,阳性率95.1%,卡痕率98.3%,PPD反应平均直径9.8±3.4mm,卡痕平均直径4.7±1.3mm,随着卡痕增大阳转率依序提高。[结论]本市区新生儿BCG接种工作质量已达较高水平,多种监测指标均稳定达标。     

脑型疟疾误诊1例分析

对脑型疟疾误诊1例分析如下. 1 病历摘要 男,36岁.因"畏寒、发热、头痛7 d,意识不清1 d"以"中枢神经系统感染"急诊收入院.当地医院予抗感染治疗7 d,症状无好转.患者为个体司机,经常往返于云南、广西等地.起病前10 d曾到过云南瑞丽.入院查体:T 38.2 ℃,神志不清,呼之不应,皮肤、巩膜轻度黄染.颈阻(+).双肺呼吸音粗,未闻及干湿罗音.腹软,肝脾未扪及,病理征未引出,余未见异常.     

尼日尔国脑型疟疾206例临床分析

目的 探讨非洲脑型疟疾的临床特点及诊疗措施.方法 对206例脑型疟疾的资料进行总结分析.结果 根据临床表现、周围血象涂片及骨髓涂片找到疟原虫即可以诊断.结论 早期诊断,及时使用足量高效的抗疟疾药物,同时治疗并发症及基础病,是提高治愈率及降低病死率的关键.     

Treg/Th17在不明原因复发性流产中的作用机制北大核心CSCD

妊娠是一个复杂的生理过程,母-胎免疫失衡与不明原因复发性流产等多种妊娠并发症有关。在母-胎界面,介导免疫耐受的调节性T细胞(Treg)和具有促炎作用的Th17细胞,起源上有同源性,功能上可能互相拮抗,在一定条件下可相互转化,其表达失衡可能和不明原因复发性流产有关。本文就Treg、Th17细胞在不明原因复发性流产中的作用机制作一综述。     

γδT细胞在致死型约氏疟原虫感染BALB/c小鼠中作用

  目的  探讨 γδT细胞在感染致死型约氏疟原虫（P.y 17XL）的BALB/c小鼠免疫应答中作用及机制。  方法  6～8周雌性BALB/c小鼠随机分为对照组、P.y 17XL感染组和 γδT消除组。小鼠经腹腔注射P.y 17XL感染红细胞1 × 10⁶个/只。γδT消除方法为感染前连续2 d腹腔注射TCR γ/δ 单抗（150 μg/只）,对照组和P.y 17XL感染组注射等体积同型对照抗体。动态检测红细胞感染率并观察小鼠生存率。感染后3、5 d,制备脾细胞悬液,流式细胞术检测γδT、DCs和Th1细胞数量;体外培养脾细胞,48 h后收集上清,ELISA检测 γ 干扰素（IFN-γ）和肿瘤坏死因子 α（TNF-α）水平。  结果  与对照组比较,感染后3、5 d,P.y 17XL感染组小鼠脾脏中 γδT细胞数量明显升高（P < 0.05）,消除组小鼠脾脏中 γδT细胞数量明显降低（P < 0.01）。感染后5 d,与感染组比较,γδT消除组小鼠脾脏中DC细胞数量及活化水平明显增加,IFN-γ 和TNF-α 含量明显升高,Th1细胞数量明显增加。  结论  γδT细胞参与P.y 17XL红内期急性期感染;消除 γδT细胞后,Th1型免疫应答代偿性增加。     

细胞因子与复发性流产的相关性研究进展

<正>常妊娠依赖于母体内细胞因子参与的免疫调控以产生母胎免疫耐受。近年来研究发现复发性流产(recurrent spontaneous abortion,RSA)患者体内存在Th 1/Th 2型细胞因子失衡现象,正常妊娠是以Th 2细胞免疫为主,RSA则以Th 1细胞免疫为主。任何影响Th 1/Th 2细胞比例的因素均可导致流产。随着对细胞因子研究的进展,发现传统Th 1/Th 2细胞模式不能完全解释母胎免疫耐受机制,由此提出了Th 1/Th 2/Th 17及调节性T细胞(regulatory T cell,Treg)模式。研究发现Th 17/Treg比例失衡,影响母体外周血及子宫蜕膜局部细胞因子间的网络平衡,导致流产发生。针对细胞因子的免疫调节治疗(如淋巴细胞免疫治疗、IVIG、TNF-α抑制剂等)可调整T细胞亚群比例及其细胞因子的分泌水平。本文将对Th 1/Th 2/Th 17及Treg模式与RSA的关系进行综述。     

Th17/Treg细胞与妊娠期高血压疾病关系及其防治研究进展

妊娠期高血压疾病(HDP)是妊娠期特有的疾病,严重威胁母婴安全,发病原因至今未明。妊娠是类似于同种异体移植的复杂生理过程,母胎之间的免疫耐受是妊娠得以维持的关键。新近发现,调节性T(Treg)细胞介导的免疫耐受能力下降,和辅助性T细胞17(Th17)介导的免疫反应增强,是导致妊娠期高血压疾病发生的重要原因,两类细胞之间平衡的打破可能是多种疾病发生的重要原因。近年来,Treg细胞"主动"抑制机制在免疫耐受中的作用越来越受到重视,而利用特异性IL-17单克隆抗体体内干预自身免疫性疾病、器官移植以及肿瘤也是研究的热点,现对相关内容及进展进行综述。     

脑型疟小鼠小胶质细胞的活化特征分析

目的　利用血脑屏障分隔小胶质细胞与外周巨噬细胞,探讨小胶质细胞在实验型脑型疟（experimental cerebral malaria, ECM）发生中的活化特征。方法　利用依文思兰渗出法确定ECM小鼠血脑屏障开放时间,在不同感染时间点,采用流式细胞技术和间接免疫荧光法检测小胶质细胞的活化特征,采用实时荧光定量PCR技术检测炎症和活化因子的变化。结果　ECM小鼠血脑屏障显著开放始于感染后第6 d。感染后第5 d,脑内促炎因子、巨噬细胞活化相关因子的转录水平以及CD11b+、CD45+细胞的占比和数目均显著上调。CD11b+细胞可根据CD45表达量分群,其中CD45high亚群占比在感染后第5 d下调而第7 d上调。结论　小胶质细胞参与ECM小鼠脑内炎症反应,且其活化与CD45表达量相关,CD11b+CD45high可作为活化小胶质细胞的标志物。     

In vitro culture medium influences the vaccine efficacy of Mycobacterium bovis BCG

The varied rates of protection induced by Mycobacterium bovis BCG vaccine against tuberculosis has been attributed to many factors such as genetic variability among BCG strains, rapid clearance of BCG in some populations, and different levels of previous exposure of vaccinated populations to environmental mycobacteria. However, the methods and conditions employed to prepare this vaccine for human usage by various manufacturers have not been investigated as potential factors contributing to the variation in vaccine efficacy. A review of the literature indicates discrepancies between the approach for growing BCG vaccine in the laboratory to assess immune responses and protective ability in animal models, and that employed for production of the vaccine for administration to humans. One of the major differences is in the growth medium used for routine propagation in the laboratory and the one used for bulk vaccine production by manufacturers. Here we compared the immunogenicity of the BCG vaccine grown in Middlebrook 7H9 medium, the most commonly used medium in laboratory studies, against that grown in Sauton medium, which is used for growing BCG by most manufacturers. Our results showed clear differences in the behavior of BCG grown in these different culture media. Compared to BCG grown in Middlebrook 7H9 medium, BCG grown in Sauton media was more persistent inside macrophages, more effective at inhibiting apoptosis of infected cells, induced stronger inflammatory responses and stimulated less effective immunity against aerosol challenge with a virulent Mtb strain. These findings suggested that the growth medium used for producing BCG vaccine is an important factor that deserves increased scrutiny in ongoing efforts to produce more consistently effective vaccines against Mtb.     

黄芪多糖对肝癌Hep G2.215细胞的抑制作用及其机制研究

目的　分析TFRs占Tregs的比例与HIV感染疾病进展的关系。方法　以2016—2020年于汉中三二〇一医院门诊就诊及随访的94例HIV感染者（包括未治疗者,抗病毒治疗免疫重建成功和免疫重建失败者）及性别、年龄等相匹配的健康对照为研究对象。将CD3+CD4+Foxp3+ T细胞定义为调节性T细胞（regulatory T cells, Tregs）,将CD3+CD4+CXCR5+Foxp3+ T细胞定义为滤泡调节性T细胞（follicular regulatory T cells, TFRs）,分析TFRs占Tregs的比例与HIV RNA及CD4+ T细胞计数之间的关系,并对比分析其在免疫重建成功与免疫重建失败HIV感染者之间的差异。结果　TFRs/Tregs比值与HIV RNA呈负相关（r=-0.276,P＜0.05）,与CD4+ T细胞计数呈正相关（r=0.579,P＜0.05）。结论　HIV感染者TFRs占Tregs的比例越高,机体的免疫状态有可能越好。     

维生素Ｅ对1，2-二氯乙烷中毒性脑水肿保护作用的研究

目的探讨维生素E (vitamin E,Vit E)对1,2-二氯乙烷(1,2-dichloroethane,1,2-DCE)中毒性脑水肿的保护作用。方法将雌性昆明种小鼠随机分为空白对照组、Vit E对照组、1,2-DCE单纯染毒组及Vit E低、中和高剂量干预组。连续给予药物灌胃4 d后,采取静式吸入方式染毒3. 5 h/d,持续3 d。结果与空白对照组相比,单纯染毒组小鼠脑组织呈现明显脑水肿病理改变,脑含水量、脑组织中丙二醛(malondialdehyde,MDA)含量及细胞色素P450 2E1 (cytochrome P450 2E1,CYP2E1)蛋白和mRNA表达水平显著升高,脑组织中还原型谷胱甘肽(glutathione,GSH)含量、超氧化物歧化酶(superoxide dismutase,SOD)和过氧化氢酶(catalase assay kit,CAT)活性、Occludin蛋白和mRNA及Claudin 5蛋白表达水平显著降低。与单纯染毒组相比,各干预组小鼠的脑含水量、脑组织MDA含量、CYP2E1蛋白和mRNA表达水平显著降低,GSH含量、Occludin蛋白及mRNA水平显著升高;中和高剂量干预组的小鼠脑组织中SOD和CAT活性及Claudin 5蛋白表达水平亦显著升高(P0. 05)。结论单纯1,2-DCE染毒可引起小鼠脑水肿,诱导脑组织中CYP2E1的表达,诱发脑组织氧化损伤,破坏紧密连接蛋白,并抑制Occludin和Claudin 5的表达;而Vit E干预可显著抑制CYP2E1的表达,缓解CYP2E1介导的氧化损伤,有效预防1,2-DCE引起的中毒性脑水肿。     

Differential protective effect of bacillus Calmette-Guerin vaccine against multibacillary and paucibacillary leprosy in Nagpur, India

For this paper we conducted a secondary data analysis to test the hypothesis that a linear trend exists in the protective effect of bacillus Calmette-Guerin (BCG) vaccine against types of leprosy. We used data from two previous case-control studies to perform an unmatched test for linear trend. We observed that both the studies revealed a significant linear trend (P<0.00001). One study that estimated an insignificant protective effect of BCG against paucibacillary leprosy showed a significant departure from linearity. We conclude that, the protective effect of BCG vaccination is differential across severity of leprosy as it brings about a shift in the immune response to a higher level of cell mediated immunity. We recommend that future studies dealing with the protective effect of BCG against leprosy should also conduct an analysis for trend.     

MUC1基因疫苗对乳腺肿瘤抑制的实验研究

目的:研究人粘蛋白MUC1基因DNA疫苗诱导小鼠体内免疫应答及对乳腺肿瘤的特异性抑制作用。方法:采用股四头肌注射法接种PcDNA3.1(+)-MUC1质粒,通过ELISA法检测小鼠血清MUC1抗体、脾细胞产生IL-2和IFN-γ的量及血清中TNF水平,通过乳酸脱氢酶释放法测定CTL对MCF-7细胞的杀伤活性。结果:经PcDNA3.1(+)-MUC1免疫小鼠后脾细胞分泌IL-2、IFN-γ及血清TNF水平较对照组明显增高,差异有统计学意义;在效靶比为100∶1、50∶1、25∶1、12.5∶1时,MUC1基因疫苗免疫组小鼠CTL对人乳腺癌细胞系MCF-7杀伤率分别为63.8%、51.2%、43.5%、22.5%,较空载体PcDNA3.1(+)组小鼠和灭菌生理盐水组小鼠均明显升高,差异有统计学意义(P<0.05)。结论:MUC1基因DNA疫苗能够激活小鼠Th1细胞,诱导小鼠产生抗MUCl特异性抗体,诱导产生杀伤高表达MUC1基因的乳腺癌细胞的CTL,为MUC1基因疫苗用于乳腺肿瘤生物治疗提供了一定的实验依据。     

Genetic linkage of autologous T cell epitopes in a chimeric recombinant construct improves anti-parasite and anti-disease protective effect of a malaria vaccine candidate

We have reported the design of polyvalent synthetic and recombinant chimeras that include promiscuous T cell epitopes as a viable delivery system for pre-erythrocytic subunit malaria vaccines. To further assess the ability of several Plasmodium T cell epitopes to enhance vaccine potency, we designed a synthetic gene encoding four Plasmodium yoelii merozoite surface protein 1 (PyMSP1) CD4⁺ promiscuous T cell epitopes fused in tandem to the homologous carboxyl terminal PyMSP1₁₉ fragment. This Recombinant Modular Chimera (PyRMC-MSP1₁₉) was tested for immunogenicity and protective efficacy in comparative experiments with a recombinant protein expressing only the PyMSP1₁₉ fragment. Both proteins induced comparable antibody responses. However PyRMC-MSP1₁₉ elicited higher anti-parasite antibody titers and more robust protection against both hyper-parasitemia and malarial anemia. Most importantly, passive transfer of anti-PyRMC-MSP1₁₉, but not anti-PyMSP1₁₉ antibodies protected against heterologous challenge. These studies show that protective efficacy can be significantly improved by inclusion of an array of autologous promiscuous T cell epitopes in vaccine constructs.     

鱼油脂肪乳对重症脑卒中病人免疫功能的影响

目的:探讨鱼油脂肪乳对重症脑卒中病人康复过程中免疫功能的影响。方法:将86例符合入组条件的重症脑卒中病人随机分为观察组(添加鱼油脂肪乳治疗,n=46)和对照组(常规营养治疗,n=40),其他治疗两组无差异。通过检测两组治疗前和治疗后2周免疫球蛋白(Ig G、Ig A、Ig M)、血总淋巴细胞计数(TLC)和T细胞亚群(CD3+、CD3+CD4+、CD3+CD8+、CD4+/CD8+)水平,并对两种治疗方法的结果进行比较。结果:治疗前两组病人各指标无显著性差异。2周后,观察组病人Ig G、Ig A、Ig M和TLC高于对照组,其中Ig G、Ig M和TLC明显升高(P0.05)。T细胞亚群水平中CD3+、CD3+CD4+、CD4+/CD8+水平明显高于对照组(P0.05),而抑制T细胞(CD3+CD8+)的计数无明显变化(P0.05)。结论:鱼油脂肪乳在重症脑卒中病人的康复过程中起着调节和改善免疫功能的作用。     

The influence of BCG vaccine strain on mycobacteria-specific and non-specific immune responses in a prospective cohort of infants in Uganda

Background

Globally, BCG vaccination varies in efficacy and has some non-specific protective effects. Previous studies comparing BCG strains have been small-scale, with few or no immunological outcomes and have compared TB-specific responses only. We aimed to evaluate both specific and non-specific immune responses to different strains of BCG within a large infant cohort and to evaluate further the relationship between BCG strain, scarring and cytokine responses.

Methods

Infants from the Entebbe Mother and Baby Study (ISRCTN32849447) who received BCG-Russia, BCG-Bulgaria or BCG-Denmark at birth, were analysed by BCG strain group. At one year, interferon-gamma (IFN-γ), interleukin (IL)-5, IL-13 and IL-10 responses to mycobacteria-specific antigens (crude culture filtrate proteins and antigen 85) and non-mycobacterial stimuli (tetanus toxoid and phytohaemagglutinin) were measured using ELISA. Cytokine responses, scar frequency, BCG associated adverse event frequency and mortality rates were compared across groups, with adjustments for potential confounders.

Results

Both specific and non-specific IFN-γ, IL-13 and IL-10 responses in 1341 infants differed between BCG strain groups including in response to stimulation with tetanus toxoid. BCG-Denmark immunised infants showed the highest cytokine responses. The proportion of infants who scarred differed significantly, with BCG scars occurring in 52.2%, 64.1% and 92.6% of infants immunised with BCG Russia, BCG-Bulgaria and BCG-Denmark, respectively (p < 0.001). Scarred infants had higher IFN-γ and IL-13 responses to mycobacterial antigens only than infants without a scar. The BCG-Denmark group had the highest frequency of adverse events (p = 0.025). Mortality differences were not significant.

Conclusions

Both specific and non-specific immune responses to the BCG vaccine differ by strain. Scarring after BCG vaccination is also strain-dependent and is associated with higher IFN-γ and IL-13 responses to mycobacterial antigens. The choice of BCG strain may be an important factor and should be evaluated when testing novel vaccine strategies that employ BCG in prime–boost sequences, or as a vector for other vaccine antigens.     

Impact of in vitro evolution on antigenic diversity of Mycobacterium bovis bacillus Calmette-Guerin (BCG)

Mycobacterium bovis bacillus Calmette-Guerin (BCG), the only vaccine currently used against tuberculosis, is an attenuated derivative of M. bovis that has been propagated in vitro for more than 40 years. We have previously reported that the experimentally-verified human T cell epitopes of the M. tuberculosis complex (MTBC) are the most conserved elements of the genome; whether immune recognition is the force driving the conservation of epitopes in the MTBC is unknown. Therefore, we sequenced the genomes of 12 BCG strains to determine whether T cell epitopes were under selection pressure during BCG in vitro evolution. We constructed a genome-wide phylogeny and refined the previously-determined BCG phylogeny. Notably, we identified a new cluster between BCG Japan and BCG Russia, and repositioned the relationships of several strains within the lineage. We also compared the sequence diversity of 1530 experimentally verified human T cell epitopes in the BCG vaccines with those in the MTBC. We found 23% of the known T cell epitopes are absent, and that the majority (82%) of the absent epitopes in BCG are contained in 6 proteins encoded in 2 regions of difference (RD) unique to BCG strains. We also found that T cell epitope sequences in BCG are more conserved than non-epitope sequences in the same gene. Finally, we find evidence that epitope sequence variation in BCG potentially affects human T cell recognition. These findings provide new insight into sequence variation in a slow-growing bacterium closely related to the MTBC that has been subjected to prolonged passage outside of a mammalian host, and indicate little difference in the extent of variation in vivo and in vitro.