Minocycline attenuates HIV‐1 infection and suppresses chronic immune activation in humanized NOD/LtsZ‐scidIL‐2Rγnull mice

More than a quarter of a century of research has established chronic immune activation and dysfunctional T cells as central features of chronic HIV infection and subsequent immunodeficiency. Consequently, the search for a new immunomodulatory therapy that could reduce immune activation and improve T‐cell function has been increased. However, the lack of small animal models for in vivo HIV study has hampered progress. In the current study, we have investigated a model of cord blood haematopoietic progenitor cells (CB‐HPCs) ‐transplanted humanized NOD/LtsZ‐scidIL‐2Rγ^null mice in which progression of HIV infection is associated with widespread chronic immune activation and inflammation. Indeed, HIV infection in humanized NSG mice caused up‐regulation of several T‐cell immune activation markers such as CD38, HLA‐DR, CD69 and co‐receptor CCR5. T‐cell exhaustion markers PD‐1 and CTLA‐4 were found to be significantly up‐regulated on T cells. Moreover, increased plasmatic levels of lipopolysaccharide, sCD14 and interleukin‐10 were also observed in infected mice. Treatment with minocycline resulted in a significant decrease of expression of cellular and plasma immune activation markers, inhibition of HIV replication and improved T‐cell counts in HIV‐infected humanized NSG mice. The study demonstrates that minocycline could be an effective, low‐cost adjunctive treatment to regulate chronic immune activation and replication of HIV.     

Complex Deregulation and Expression of Cytokines and Mediators of the Immune Response in Parkinson's Disease Brain is Region Dependent

Neuroinflammation is common in neurodegenerative diseases including Parkinson disease (PD). Expression of 25 mRNAs was assessed with TaqMan‐PCR including members of the complement system, colony stimulating factors, Toll family, cytokines IL‐8, IL‐6, IL‐6ST, IL‐1B, TNF‐α family, IL‐10, TGFβ family, cathepsins and integrin family, in the substantia nigra pars compacta, putamen, frontal cortex area 8 and angular gyrus area 39, in a total of 43 controls and 56 cases with PD‐related pathology covering stages 1–6 of Braak. Up‐regulation of IL‐6ST was the only change in the substantia nigra at stages 1–2. Down‐regulation of the majority of members examined occurred in the substantia nigra from stage 4 onwards. However, region‐dependent down‐ and up‐regulation of selected mRNAs occurred in the putamen and frontal cortex, whereas only mRNA up‐regulated mRNAs were identified in the angular cortex from stage 3 onwards in PD cases. Protein studies in frontal cortex revealed increased IL6 expression and reduced IL‐10 with ELISA, and increased IL‐6 with western blotting in PD. Immunohistochemistry revealed localization of IL‐5, IL‐6 and IL‐17 receptors in glial cells, mainly microglia; IL‐5, IL‐10 and M‐CSF in neurons; TNF‐α in neurons and microglia; and active NF‐κB in the nucleus of subpopulations of neurons and glial cells in PD. Distinct inflammatory responses, involving pro‐ and anti‐inflammatory cytokines, and variegated mediators of the immune response occur in different brain regions at the same time in particular individuals. Available information shows that altered α‐synuclein solubility and aggregation, Lewy body formation, oxidative damage and neuroinflammation converge in the pathogenesis of PD.     

结核感染T细胞斑点试验联合胸腔积液Xpert MTB/RIF检测诊断结核性胸腔积液的价值

目的评估结核感染T细胞斑点试验（T-SPOT.TB）联合胸腔积液结核分枝杆菌/利福平耐药实时荧光定量核酸扩增检测技术(Xpert MTB/RIF) 在结核性胸腔积液的诊断价值。方法收集胸腔积液患者112例,其中确诊或临床诊断为结核性胸腔积液76例,非结核性胸腔积液36例。所纳入患者治疗前均行胸腔积液T-SPOT.TB、血T-SPOT.TB、胸腔积液Xpert MTB/RIF、胸腔积液腺苷脱氨酶（ADA）检测,并对其检测结果进行分析。结果胸腔积液T-SPOT.TB诊断结核性胸腔积液的敏感度（97.37%,74/76),高于外周血T-SPOT.TB （76.32%,58/76）、胸腔积液Xpert MTB/RIF（65.79%,50/76）和胸腔积液ADA（28.95%,22/76）,差异均有统计学意义（χ2=14.74、25.22、76.45,P<0.01）。胸腔积液Xpert MTB/RIF检测的特异度（100%,36/36）均高于胸腔积液T-SPOT.TB（77.78%,28/36）、外周血T-SPOT.TB（55.56%,20/36）和胸腔积液ADA（50.00%, 18/36）,差异均有统计学意义（χ2=6.89、20.57、24.00,P均＜0.01）。胸腔积液T-SPOT.TB和胸腔积液Xpert MTB/RIF联合检测的敏感度（64.47%, 49/76）低于胸腔积液T-SPOT.TB单独检测（97.37%,74/76）,差异有统计学意义（χ2=26.63,P<0.01）,但特异度由77.78%(28/36)提高至100%(36/36),差异有统计学意义（χ2=45.82,P<0.01）。结论胸腔积液T-SPOT.TB检测结核性胸腔积液具有较高的敏感度和特异度,胸腔积液T-SPOT.TB和胸腔积液Xpert Mtb/ＲIF联合检测可明显提高诊断的特异度。     

糖调节受损患者周围神经病变的电生理特点及相关因素分析

目的 研究糖调节受损（IGR）患者周围神经病变电生理特点,分析影响IGR相关神经病变的影响因素。方法 选取2016年8月—2018年8月天津市第四中心医院收治的54例IGR患者作为研究组,另选取同期在该院体检中心体检的50例健康者作为对照组。应用神经电生理检测评价两组研究对象的周围神经功能,包括神经传导检测（正中神经、尺神经、胫神经以及腓总神经/腓肠神经的波幅及传导速度）评价大纤维传导功能,皮肤交感反应（SSR）评价小纤维功能;并收集所有研究对象空腹血糖（FBG）、2?h餐后血糖（2?hPG）、糖化血红蛋白（HbA1c）、胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、血尿酸（UA）、同型半胱氨酸（Hcy）、体重指数（BMI）等相关临床生化指标,采用Logistic回归分析,计算IGR相关神经病变的影响因素。结果 研究组胫神经以及腓肠神经感觉传导速度（SCV）低于对照组（P?<0.05）。研究组下肢SSR波幅小于对照组（P?<0.05）。研究组FBG、2 hPG、HbA1c、TC、LDL-C、BMI、UA及Hcy水平高于对照组（P?<0.05）。影响IGR患者周围神经病变的因素为：TG [OlR=8.529（95% CI：1.634,43.372）]、LDL-C[（OlR=3.273（95% CI：1.202,8.927）]、BMI [OlR=1.385（95% CI：1.122,1.708）、UA [OlR=9.265（95% CI： 1.896,9.437）]及Hcy [OlR=11.336（95% CI：1.928,16.774）]。结论 IGR患者周围神经病变以小纤维及大纤维中的感觉神经髓鞘病变为主,引起IGR患者神经病变的原因可能与BMI、TC、UA、Hcy代谢紊乱引起的代谢综合征有关。     

不同糖调节水平非酒精性脂肪性肝病患者肝脏脂肪含量与胰岛β细胞功能及胰岛素抵抗的关系

目的 观察非酒精性脂肪性肝病（NAFLD）患者肝脏脂肪含量（LF）与IR及胰岛β细胞功能的关系. 方法 将286例NAFLD患者分为正常糖调节（NGR）组和IGR组,以校正CT半定量法测定LF,再根据LF分为6个亚组：NGR-1、2、3亚组及IGR-1、2、3亚组.以OGTT、胰岛素释放试验评估IR及胰岛β细胞功能,分析LF与IR及胰岛β细胞功能的关系. 结果 （1）随LF增加,NGR-2亚组△I30/△G30高于NGR-1亚组（P＜0.05）,NGR-3亚组稍低于NGR-2亚组（P＞0.05）;IGR-3亚组△I30/△G30低于IGR-1亚组（P＜0.05）;（2）随LF增加,NGR-2、3亚组HOMA-β均高于NGR-1亚组（P＜0.05）;IGR-3亚组低于IGR-1、IGR-2亚组（P＜0.05）.（3）多元线性回归分析提示,LF是影响HOMA-IR最强的独立危险因素（P＜0.01）. 结论 在NGR人群中,LF增加至5.1％～9.9％时,IR增加,胰岛β细胞早相和整体分泌代偿性增高;当LF达10.0％～20.0％时,胰岛β细胞早相分泌功能可能出现减退.对IGR人群,LF增加至5.1％～9.9％时,胰岛β细胞早相分泌功能已开始降低;当LF达10.0％～20.0％时,胰岛β细胞整体分泌功能恶化.     

益生菌联合整蛋白型肠内营养辅助治疗脓毒血症的疗效及对肠道和免疫功能的影响*

目的?探讨益生菌联合整蛋白型肠内营养辅助治疗脓毒血症的疗效及对肠道功能、炎症因子和免疫功能的影响。方法?选取2015年6月—2018年6月保定市第一中心医院西院收治的脓毒血症患者134例。随机分为观察组和对照组。对照组根据患者病情予以抗感染、液体复苏、清创引流、机械通气等治疗。在此基础上,观察组另加用双歧杆菌四联活菌片联合整蛋白型肠道营养进行支持治疗。分别观察两组治疗前和治疗3?d、10?d后APACHE-Ⅱ评分、SOFA评分、肠道功能、炎症因子水平和外周血T淋巴细胞亚群水平。结果?观察组治愈率较对照组高（P?<0.05）,病死率较对照组低（P?<0.05）。两组APACHE-Ⅱ评分、SOFA评分在不同时间、不同组间不变化趋势上有差异（P?<0.05）。观察组治疗后肠道功能评分较对照组低（P?<0.05）。两组PCT、IL-6、CRP及SAA水平在不同时间、不同组间不变化趋势上有差异（P?<0.05）。两组CD3+、CD4+和CD4+/CD8+水平在不同时间、不同组间不变化趋势上有差异（P?<0.05）。结论?益生菌联合整蛋白型肠内营养支持治疗脓毒血症,能提高疗效,改善肠道功能,并对炎症因子水平、免疫力的改善有积极作用,有效降低病死率。