Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice

In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes.     

糖尿病小鼠小肠绒毛杯状细胞分泌黏原颗粒的变化

目的：观察糖尿病小鼠小肠绒毛杯状细胞分泌的黏原颗粒是否改变,为进一步研究糖尿病的消化系统并发症提供形态学基础。方法分别选取3,5,8,10月龄db/db糖尿病小鼠及相应年龄段的db/+m正常小鼠,每组6只,标本用4%多聚甲醛灌流固定后,从距Treitz韧带约10 cm处切下一段空肠,用PAS染色方法对小肠杯状细胞分泌的黏原颗粒进行观察。结果糖尿病组小肠绒毛易被破坏,糖尿病组中杯状细胞的分泌物比同月份正常对照组显著增加(P<0.05)；糖尿病组中3月龄的杯状细胞分泌物最多,8月龄最少,并且8月龄分别与3月龄、5月龄比较均存在着显著差异(P<0.05)；正常对照组随月龄增长无显著性差异(P>0.05)。结论糖尿病时杯状细胞分泌物增多可能对小肠绒毛有保护作用。     

程序性死亡受体1和程序性死亡受体配体1在非小细胞肺癌组织中的表达情况及临床意义

目的探讨程序性死亡受体1(PD-1)和程序性死亡受体配体1(PD-L1)在非小细胞肺癌(NSCLC)组织中的表达情况及临床意义。方法选择150例NSCLC患者的NSCLC组织及其癌旁组织,采用实时荧光定量聚合酶链反应(PCR)检测两种组织中PD-1 mRNA和PD-L1 mRNA的相对表达量。采用免疫组织化学染色法检测NSCLC组织中PD-1和PD-L1的表达情况,分析PD-1和PD-L1表达情况与患者临床特征的关系。采用流式细胞术检测NSCLC组织和癌旁组织中CD4^+-PD-1、CD8^+-PD-1、CD14^+-PD-L1、CD68^+-PD-L1的表达水平。结果NSCLC组织中PD-1 mRNA和PD-L1 mRNA的相对表达量分别为(5.03±1.92)和(4.95±1.09),分别高于癌旁组织的(1.72±0.81)和(1.25±0.24),差异均有统计学意义(P﹤0.05)。TNM分期为Ⅲ~Ⅳ期、低分化、有淋巴结转移、有远处转移的NSCLC患者NSCLC组织中PD-1和PD-L1的高表达率均明显高于TNM分期为Ⅰ~Ⅱ期、高+中分化、无淋巴结转移、无远处转移的患者,差异均有统计学意义(P﹤0.01)。NSCLC组织中CD4^+-PD-1、CD8^+-PD-1、CD14^+-PD-L1、CD68^+-PD-L1的表达水平均明显高于癌旁组织,差异均有统计学意义(P﹤0.01)。结论PD-1和PD-L1在NSCLC组织中高表达,可能成为一种新的生物标志物,PD-1/PD-L1信号通路可能参与了NSCLC的免疫逃逸过程,对其逃逸机制进行研究可以为NSCLC患者的临床治疗提供新靶点。     

Immunocytochemical staining of cholinergic amacrine cells in rabbit retina

Cholinergic neurons of rabbit retina were labelled with an antibody against choline acetyltransferase, the synthesizing enzyme for acetylcholine. Two populations of cells are immunoreactive. Type a cell bodies lie in the inner nuclear layer (INL), their dendrites branching narrowly in sublamina a of the inner plexiform layer (IPL), while type b cell bodies lie in the ganglion cell layer (GCL) with dendrites branching in sublamina b of the IPL. The irregular networks of clustered immunoreactive dendrites are similar, but not identical, in the two sublaminae. Type b cells are more numerous than type a cells in central retina. No axons were stained. It appears that the immunoreactive neurons are normally placed and displaced starburst/cholinergic amacrine cells.     

P16INK4、PCNA在肺癌中表达的研究

目的 通过检测肺癌组织中p16、PCNA的表达，探讨其在肺癌发生发展中的作用及相互关系。方法 采用S—P免疫组化方法，检测83例肺癌标本及15例正常肺组织标本中P16^INK4和PCNA的表达。结果 P16^INK4和PCNA在正常肺组织和肺癌组织中表达的阳性率存在显著性差异。P16^INK4表达的阳性率在小细胞癌与非小细胞癌之间有显著性差异。PNTM分期高的肺癌标本P16^INK4及PCNA表达阳性率显著高于分期低的肺癌标本。不同分化程度的肺癌组织P16^INK4及PCNA表达阳性率有显著性差异。结论 肺癌的发生与P16^INK4的低表达和PCNA的高表达有关。而P16^INK4的表达与肺癌的组织学类型、分化程度、临床分期有关；PCNA的表达与肺癌的分化程度、临床分期有关。     

4种抗原用于斑点免疫金银染色试验诊断日本血吸虫病的比较

采用斑点免疫金银染色(Dot-IGSS)试验对4种日本血吸虫抗原的敏感性及特异性进行比较。结果显示粗提成虫抗原(AWA)、尿素溶解性成虫抗原(JWU)、硫酸铵沉淀成虫抗原(AW)和可溶性虫卵抗原(SEA)检测40例日本血吸虫病人血清抗体的敏感性均达100.0％,40例正常人血清的可疑阳性反应分别为2.5％、0、2.5％和0,40例肝吸虫病人血清的可疑交叉率分别为2.5％、0、2.5％和0,表明在高敏感的IGSS检测系统中,粗提成虫抗原的敏感性和特异性与部分纯化者和虫卵抗原无显著性差异(P>0.05)。     

Morphological types of ganglion cells in the dog and wolf retina.

The morphological types of ganglion cells in the dog and wolf retina were studied by intracellular staining with Lucifer Yellow. These retinae contain a range of ganglion cell types that closely correspond to those found in cat retina: alpha cells with large somata and large, relatively densely branched dendritic trees; beta cells with medium-sized somata and small, densely branched dendritic trees; and a variety of other types with smaller somata and varying dendritic branching patterns and dendritic field sizes. The correspondence of canine and cat ganglion cell types strengthens the view that there is a common set of ganglion cell types in carnivores. Alpha and beta cell dendritic trees of dog and wolf are monostratified in either the inner or the outer part of the inner plexiform layer, suggesting an on/off dichotomy in the response to light. Dendritic field sizes of dog alpha and beta cells increase from the central area to peripheral retina: alpha cell fields from 160-200 microns to about 1,100 microns diameter, and beta cell fields from 25 microns to about 360 microns diameter. These sizes are quantitatively very similar to those found in cat retina. The close qualitative and quantitative morphological correspondence of cat and dog ganglion cells suggests that they are also functionally very similar. It is likely that dog alpha cells have brisk-transient (Y), and dog beta cells brisk-sustained (X) concentric receptive fields. From the smallest beta cell sizes it is concluded that the visual acuity of the dog may be as good as that of the cat.     

PM2.5混悬液染尘大鼠肺银染色的组织病理学观察

目的观察PM2.5混悬液染尘大鼠的肺组织病理学改变及银染色显示肺内尘粒的效果。方法将收集的游离PM2.5制成混悬液，72只Wistar大鼠随机分为低剂量组（每0．2ml含PM2.50．3nag）、中剂量组（每0．2ml含PM2.50．75mg）、高剂量组（每0．2ml含PM2.52mg）和对照组，每组18只。3个实验组分别以不同的剂量采用支气管肺内滴入方式染尘，每周染尘1次。分别于染尘后第4、12及24周时，取肺脏，石蜡包埋组织切片进行HE染色及沃森一斯塔理（Worthin-Starry，WS）银染色观察、透射电镜（TEM）观察，对肺内尘粒进行X-线质谱元素分析（X-RSA）。计数大鼠肺内肉芽肿样病变的数目，测定肺内尘粒的沉积程度、平均积分吸光度值（IOD）和平均积分面密度值（IAD）。结果随着染毒时间的延长和染毒剂量的增大，大鼠肺内肉芽肿样病变的数目及其细胞质内尘粒的IAD值和IOD值也逐渐增高。这些尘粒在WS染色切片上呈黑褐色，更清晰；其IOD值和IAD值均明显高于HE染色下的测定值，差异有统计学意义（P〈0．05）；尘粒IOD值与肉芽肿病变数目呈正相关关系（r=0．639，P〈0．01）。TEM下大鼠肺内尘粒的超微结构与游离的PM2.5相同，X-RSA分析两者的主要元素成分也相同，均为硅元素。结论PM2.5混悬液染尘可以引起大鼠肺内出现肉芽肿样病变，WS银染色方法可以较好地显示被吞噬细胞吞噬后的PM2.5，其染色效果优于HE染色。     

颈前部皮神经构筑研究

目的　为研究皮肤疾病和损伤提供皮神经构筑资料。方法　用S 10 0蛋白免疫组化染色法研究正常成人颈前部胸锁乳突肌前、后缘皮肤各层内皮神经的数量、分布及构筑特点。结果　 ( 1)皮肤乳头层内皮神经的小分支多分布在皮突下和乳头内血管丛附近。 ( 2 )真皮网状层内神经多位于小血管附近和汗腺、皮脂腺以及毛囊周围 ,神经分支呈串珠状或波纹形。 ( 3 )皮下组织内神经干和神经网同时存在。结论　皮肤内感觉神经树的分布及构筑特点与血管树相似。     

D1S549等6个短串重复序列基因座在河南汉族群体的遗传多态性

目的　探讨河南汉族群体的D1S5 49、D3S175 4、D2 2S683和CSF1PO、TPOX、TH0 1基因座遗传多态性分布。方法　ACD抗凝血样采自 2 19名无血缘关系汉族个体 ,酚 氯仿法提取DNA ,应用复合扩增技术对D1S5 49等 6个短串重复序列 (STR)基因座进行扩增 ,采用高分辨率的聚丙烯酰胺凝胶电泳分离、银染法显影技术。统计各基因频率、计算杂合度、多态信息含量、个人识别概率及亲权否定概率。结果　 6个STR基因座基因频率的分布均符合Hardy Weinberg平衡 ,各基因座的杂合度分别为 0 .7964、0 .72 3 1、0 .815 9、0 .75 81、0 .65 2 3、0 .6816;非父排除概率为 0 .62 46、0 .4914、0 .65 0 1、0 .5 2 3 6、0 .40 98、0 .42 87;个人识别机率为 0 .8996、0 .8781、0 .92 3 1、0 .8896、0 .8167、0 .83 92 ;多态信息含量为 0 .72 16、0 .6994、0 .742 1、0 .7169、0 .65 17、0 .710 6。结论　D1S5 49等 6个STR基因座是一组高度多态性的遗传标记系统 ,在人类遗传学及法医学研究中具有重要意义