酪酸梭菌活菌散对支气管哮喘患儿辅助性T细胞17、调节性T细胞及其相关细胞因子和肠道菌群的影响

目的 探讨酪酸梭菌活菌散对支气管哮喘患儿辅助性T细胞17(Th17细胞)、调节性T细胞(Tr细胞)及其相关细胞因子和肠道菌群的影响。方法 选择2018年3月至2020年6月新乡医学院第三附属医院收治的97例支气管哮喘患儿为研究对象,根据治疗方法将患儿分为观察组(n=49)和对照组(n=48)。对照组患儿给予吸入用布地奈德混悬液、吸入用异丙托溴铵溶液和孟鲁司特钠颗粒治疗;在对照组治疗基础上,观察者组患儿给予酪酸梭菌活菌散治疗,2组患儿均治疗2个月。应用流式细胞仪检测2组患儿治疗前后Th17细胞和Tr细胞水平,并计算Th17细胞与Tr细胞的比值(Th17/Tr);采用酶联免疫吸附试验检测2组患儿治疗前后血清中白细胞介素-17(IL-17)、白细胞介素-10(IL-10)水平。使用儿童肺功能仪检测2组患儿治疗前后第1秒用力呼气容积(FEV₁)、FEV₁/用力肺活量(FVC)、呼气流量峰值(PEF)日变异率;分别于治疗前后收集并培养2组患儿新鲜粪便,观察肠道菌群分布情况。治疗期间观察2组患儿不良反应发生情况,治疗后评估患儿临床疗效;所有患儿治疗后随访...     

FANCD2、PALB2表达水平与非小细胞肺癌临床特征及预后的关系

目的 探讨范科尼贫血D2蛋白（FANCD2）、乳腺癌易感基因2定位协作蛋白（PALB2）表达水平与非小细胞肺癌（NSCLC）临床特征及预后的关系。方法 选取2017年11月—2019年10月成都市第二人民医院收治的194例NSCLC患者作为研究对象。将手术过程中取得癌组织标本作为NSCLC组,将对应的癌旁组织标本作为癌旁组,每组194例。采用免疫组织化学法检测FANCD2、PALB2在NSCLC患者癌组织及癌旁组织中的表达情况;分析FANCD2、PALB2表达与NSCLC患者临床病理特征的关系;采用Kaplan-Meier法绘制生存曲线,采用Cox比例风险模型分析探讨NSCLC患者预后的影响因素。结果 NSCLC组FANCD2、PALB2阳性率高于癌旁组（P <0.05）。Spearman相关性分析显示,NSCLC患者癌组织中FANCD2蛋白与PALB2蛋白呈正相关（r_s =0.486,P <0.05）。不同年龄、性别、吸烟、组织学分型、肿瘤直径患者FANCD2、PALB2阳性率比较,差异均无统计学意义（P >0.05）。TNM分期为Ⅲ、Ⅳ期,低分化,有淋巴结转移患者高于TNM分期为I、Ⅱ期,中/高分化,无淋巴结转移患者（P <0.05）。多因素逐步Cox回归分析结果显示：TNM分期Ⅲ、Ⅳ期［H^R=4.125,（95% CI：2.187,10.035）］、低分化［H^R=3.146,（95% CI：3.115,9.264）］、淋巴结转移［H^R=4.124,（95% CI：3.005,13.145）］、FANCD2阳性［H^R=5.146,（95% CI：3.784,12.689）］、PALB2阳性［H^R=4.563,（95% CI：2.845,7.398）］是NSCLC患者复发的影响因素（P <0.05）。多因素逐步Cox回归分析结果显示,TNM分期Ⅲ/Ⅳ期［H^R=3.689,（95% CI：2.963,11.254）］、低分化［H^R=2.167,（95% CI：1.998,5.996）］、淋巴结转移［H^R=5.648,（95% CI：3.552,12.953）］、FANCD2阳性［H^R=3.886,（95% CI：2.958,12.775）］、PALB2阳性［H^R=4.633,（95% CI：1.968,11.547）］是NSCLC患者预后的影响因素（P <0.05）。FANCD2阳性患者与阴性患者生存率比较,差异有统计学意义（P <0.05）;PALB2阳性患者与阴性患者的生存率比较,差异有统计学意义（P <0.05）。结论 FANCD2、PALB2在NSCLC患者癌组织中呈高表达,与TNM分期、分化程度、淋巴结转移密切相关,可作为辅助评估患者预后和复发的潜在标志物。     

巨噬细胞程序性死亡在动脉粥样硬化中的研究进展

动脉粥样硬化（AS）是大多数心血管疾病的主要病理基础,是一种由于脂质沉积、泡沫细胞形成等多种因素诱发的慢性无菌性炎症过程。巨噬细胞作为AS病变的主要免疫细胞群,在所有阶段都发挥着关键作用。因此,调控巨噬细胞活动可能成为调节AS进程的有效方法。近年来,随着对细胞程序性死亡的研究逐渐深入,巨噬细胞程序性死亡在AS的发生、转归过程中的重要作用逐渐成为热点。巨噬细胞程序性死亡是由胞内相关基因调控的分子程序所介导的死亡过程,包括凋亡、焦亡、自噬、坏死性凋亡、铁死亡及PARP-1依赖性细胞死亡等。该文对巨噬细胞程序性死亡的基本机制及其各种程序性死亡间的相互作用在AS中的研究进展进行综述,为AS的防治提供新策略。     

白藜芦醇对脑小血管疾病大鼠神经细胞损伤及免疫因子白细胞介素-6、白细胞介素-10水平的影响

目的 探究白藜芦醇对脑小血管疾病（CSVD）大鼠神经细胞损伤及免疫因子白细胞介素-6(IL-6)、白细胞介素-10(IL-10)水平的影响。方法 将60只CSVD大鼠分为假手术组、模型组和治疗组,每组20只。通过水迷宫实验测试大鼠神经认知功能,HE染色观察大鼠海马组织病理学改变,TUNEL染色检测大鼠海马组织神经细胞凋亡率,Western blotting检测大鼠海马组织BAX/BCL-2、IL-6、IL-10蛋白的表达,酶联免疫吸附试验（ELISA）检测外周血IL-6、IL-10、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽（GSH）和丙二醛（MDA）水平。结果 模型组大鼠神经行为评分高于治疗组（P <0.05）。模型组大鼠穿越次数和停留时间少于假手术组（P <0.05）,治疗组大鼠穿越次数和停留时间较模型组增加（P <0.05）。模型组大鼠海马组织神经细胞凋亡率、BAX/BCL-2蛋白表达比值高于假手术组（P <0.05）,治疗组大鼠海马组织神经细胞凋亡凋亡率、AX/BCL-2蛋白表达比值低于模型组（P <0.05）。与假手术组比较,模型组...     

Skin-infiltrating lymphocytes in normal and disordered skin: activation signals and functional roles in psoriasis and mycosis fungoides-type cutaneous T cell lymphoma.

T lymphocytes recruited into the skin can experience several different outcomes. On the one hand, they may be recruited by adhesion molecules and chemoattractants to enter the perivascular space, but never undergo activation. Other T cells undergo activation and further differentiation under the influence of the cutaneous milieu. These activated lymphocytes then coordinate specific and non-specific immune responses characteristic of inflamed tissue. We have explored two models for studying the activation and function of skin infiltrating T lymphocytes (SIL's). In the first model, we have identified a family of Langerhans cell-related professional dendritic antigen presenting cells that exist in the epidermis and dermis of normal skin, atopic skin, and mycosis fungoides skin. These have APC abilities to activate freshly recruited resting blood T cells that are distinct from another family of macrophage-related cells abnormally present in sunburned or psoriatic skin. In the second model, we examined the function of cells that have already been recruited into the skin of patients with psoriasis and mycosis fungoides. Lesional psoriasis and mycosis fungoides T cells exhibited a variety of T cell receptor gene rearrangements, conclusively demonstrating that heterogeneous populations of T lymphocytes exist in inflamed human skin. From psoriasis, clones were identified that were particularly effective at inducing normal keratinocytes to assume "psoriatic" phenotypic features and functions. Thus, lesional psoriatic SIL's could induce HLA-DR, ICAM, and CDw60 on normal keratinocytes. In addition, psoriatic SIL's induced increased keratinocyte proliferation and cytokine profile changes characteristic of psoriatic epidermis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transneuronal labeling of cochlear nucleus neurons by HRP-labeled auditory nerve fibers and olivocochlear branches in mice.

Auditory nerve fibers were labeled by extracellular injections of horseradish peroxidase into the spiral ganglion in mice. The labeled fibers were traced in an anterograde direction through the auditory nerve into the cochlear nucleus. In almost half of the injections, the labeled endings of auditory nerve fibers contacted cochlear nucleus neurons that were also labeled with horseradish peroxidase and were presumably transneuronally labeled. Only darkly labeled endings were associated with transneuronally labeled neurons, but not all darkly labeled endings had targets that were transneuronally labeled. Transneuronal labeling occurred almost exclusively in the ventral cochlear nucleus, often between endbulbs and bushy cells. Both "modified" endbulbs and the larger endbulbs of Held transneuronally labeled the bushy cells that they contacted. At the ultrastructural level, transneuronal labeling was evident as a darkening of ribosomes and the membrane surfaces of mitochondria, endoplasmic reticulum, and the nucleus. Transneuronal labeling occurred rarely in octopus, small, and stellate cells, and in neurons of the dorsal cochlear nucleus. Spiral ganglion injections also label olivocochlear fibers, efferent fibers that pass through the ganglion en route to the hair cells. These fibers give off branches to the cochlear nucleus that were rarely associated with transneuronal labeling. In eight instances, the targets of olivocochlear branches were stellate cells or small cells. We suggest that in our mouse preparation, horseradish peroxidase is effective as a transneuronal marker because the short distance from injection site to the cochlear nucleus results in a high concentration of horseradish peroxidase in the endings of the auditory nerve fibers.     

Development of glutamic acid decarboxylase-immunoreactive elements in the cerebellar cortex of normal and lurcher mutant mice.

The development of glutamic acid decarboxylase-immunoreactivity (GAD-IR) in cells, fibers, and varicosities of the cerebellar cortex has been examined by light microscopy in normal and lurcher mutant mice between postnatal day 3 and 30 (P3-P30). Purkinje cell morphology was demonstrated in adjacent sections by using an antiserum to the 28Kd vitamin D-dependent calcium binding protein (CaBP). In early postnatal lurcher mice, but not in normal littermates, GAD-IR fibers, presumably Purkinje cell pseudopodia, invade the external granular layer. The plexus of CaBP-IR axons in the internal granular layer is much less complex in lurcher mice than in normal littermates, even before the onset of lurcher Purkinje cell degeneration at P8. In normal mice, GAD-IR fibers encapsulate Purkinje cell somata by P15. Lurcher Purkinje cells, in contrast, receive scattered contacts by GAD-IR puncta and possess a "cap" of such elements surrounding the primary dendrite and apical soma. Pinceau formations, visible as a knot of GAD-IR puncta hanging from the base of Purkinje cells in normal P15 mice, are not present in lurcher littermates. "Empty baskets" or collapsed pinceau formations in regions devoid of Purkinje cells are not revealed by anti-GAD immunohistochemistry in the P17-P30 lurcher cerebellar cortex.     

Ia-expressing microglial cells in experimental allergic encephalomyelitis in rats

Summary Monoclonal antibodies (MRC OX-6 and OX-17) recognized three types of cells expressing Ia antigen during the course of acute experimental allergic encephalomyelitis (EAE) in rats. In earlier stages of the disease, in animals with or without paralysis, Ia antigens were mostly localized to subarachnoidal and perivascular lymphocytic and histiocytic cell infiltrates, possibly serving as antigen-presenting cells. On the other hand, in convalescent rats, Ia antigens were expressed in a large number of cells with dendritic processes heavily populating the spinal gray matter. The appearance of these Ia-expressing cells in the convalescent stage coincided with the development of degenerating axon terminals in the spinal gray matter. These Ia-expressing cells possessed morphological features characteristic of microglia and were positive for ML-1 lectin but did not express glial fibrillary acidic protein. Immune electron microscopy disclosed the presence of Ia reaction products in the Golgi apparatus, endoplasmic reticulum and plasma membrane of these cells with dendritic processes, indicating active synthesis of Ia molecules in microglia. In addition, Ia antigens were localized to the cells with ultrastructural features of macrophages. Thus, Ia-expressing cells in EAE seems to play dual roles: the induction of immunological reactions during earlier stages and the participation in reparative processes during convalescence.Supported by Grants-in-aid from the Ministry of Health and Welfare for Intractable Neuroimmunological Diseases and from the Ministry of Education, Science and Culture (Project 61570380 to HK)     

Transient GABA immunoreactivity in cranial nerves of the chick embryo

The distribution and time course of gamma-aminobutyric acid (GABA) immunoreactivity was investigated in the cranium of the chick embryo from 2 to 16 days of incubation (E2-16). A fraction of nerve fibers transiently stains GABA-positive in all cranial motor nerves and in the vestibular nerve. Cranial motor nerves stain GABA-positive from E4 to E11, including neuromuscular junctions at E8-11; labeled fibers are most frequent in the motor trigeminal root (E6-9.5). Substantial GABA staining is present from E4 to E10 in a subpopulation (1-2%) of vestibular ganglion cells. Their peripheral processes are labeled in the vestibular endorgan, predominantly in the posterior crista. Some GABA-positive fibers are present in the olfactory nerve (after E5) and in the optic nerve (after E9.5); their immunoreactivity persists throughout the period investigated. Transient GABA immunoreactivity follows "pioneer" fiber outgrowth and coincides with the formation of early synaptic contacts. GABA-containing neurons may change their neuronal phenotype (loss of GABA expression) or they may be eliminated by embryological cell death. Periods of cell death were determined in cranial ganglia and motor nuclei by aggregations of pycnotic cells in the same embryonic material. The periods of embryonic cell death partly coincide with transient GABA immunoreactivity. The function(s) of transient GABA expression is unknown. Some lines of evidence suggest that GABA has neurotrophic functions in developing cranial nerves or their target tissue. In the developing neuromuscular junction, GABA may be involved in the regulation of acetylcholine receptors.