榄香烯抗肝癌作用的实验研究

目的研究榄香烯对小鼠移植性肝癌(H22)的抗肿瘤作用及其机制。方法建立小鼠移植性肿瘤模型(H22肝癌),腹腔注射不同剂量的榄香烯,观察其抗肿瘤作用(抑瘤率),以免疫学方法检测小鼠治疗后的细胞免疫功能的改变(IL2、T淋巴细胞转化能力),并通过免疫组化的方法检测肿瘤组织癌基因(p53和Bcl-2)的表达。结果榄香烯具有明显的抑瘤作用,抑瘤作用的主要机制是增强小鼠的细胞免疫功能,促进肿瘤细胞凋亡和调节癌基因的表达。结论榄香烯具有显著的抑瘤作用,其作用机制是通过提高荷瘤小鼠机体免疫功能和诱导肿瘤细胞凋亡两条途径来抑制肿瘤的生长。     

益气活血通络方治疗冠心病疗效及其对血管内皮功能和免疫调节的影响

【目的】探讨益气活血通络法治疗冠心病的疗效以及对血管内皮功能、免疫调节的影响。【方法】将82例冠心病患者随机分为治疗组和对照组各41例,对照组给予常规西药治疗,治疗组在对照组基础上加服益气活血通络方,比较2组心绞痛疗效、心电图疗效和临床症状疗效,观察2组治疗前后血浆血管内皮生长因子(VEGF)、内皮素-1(ET-1)及超敏C反应蛋白(hs-CRP)、白细胞介素-1β(IL-1β)等指标的变化情况。【结果】(1)治疗后,2组心绞痛疗效及心电图疗效比较,差异无统计学意义(P>0.05);临床症状疗效方面,治疗组优于对照组(P<0.05)。(2)治疗后,治疗组VEGF含量显著升高,ET-1含量显著下降(P<0.01);对照组治疗前后VEGF、ET-1含量比较,差异均无统计学意义(P>0.05);治疗组在改善VEGF、ET-1含量方面均显著优于对照组(P<0.01)。(3)治疗后,治疗组hs-CRP、IL-1β含量均显著下降(P<0.01);对照组hs-CRP、IL-1β含量均有下降趋势,但差异均无统计学意义(P>0.05);治疗组在改善hs-CRP、IL-1β含量方面均显著优于对照组(P<0.01)。【结论】对冠心病心绞痛患者,在常规西药治疗的基础上加用益气活血通络法治疗,能更好地达到缓解心绞痛、改善临床症状的目的,这可能与其改善血管内皮功能和免疫调节功能等有关。     

炎症性肠病合并神经内分泌肿瘤的临床特征分析

报道1例炎症性肠病（inflammatory bowel disease,IBD）合并神经内分泌肿瘤（neuroendocrine neoplasms,NENs）病例,结合文献报道的69例病例,总结分析IBD合并NENs的临床特征,探索两者之间的关系。69例IBD合并NENs患者中包括32例克罗恩病（Crohn disease,CD）及37例溃疡性结肠炎（ulcerative colitis,UC）,男女发病率相当（P=0.151）。NENs多形成于IBD之后。CD患者发生NENs的中位病程为4.5年,小于UC患者的17年（P=0.002）。33例患者为术后或随访时发现NENs,有症状者中11例表现为肠梗阻。NENs好发部位与IBD相似,CD患者好发于回肠和阑尾（27例）,而UC患者好发于结直肠（31例）（P<0.001）。CD患者中神经内分泌瘤更常见（26例）,神经内分泌癌则在UC患者中更普遍（22例）（P<0.001）。IBD可合并或并发NENs,临床表现无特异性,病因尚不明确,有待进一步探索。     

Ouabain pre-treatment modulates B and T lymphocytes and improves survival of melanoma-bearing animals

Ouabain (OUA) is a glycoside shown to modulate B and T lymphocytes. Nevertheless, ouabain effects on B16F10 melanoma immune response, a mouse lineage that mimics human melanoma, are still unknown. Our aim was to study how OUA in vivo treatment modulates lymphocytes and if it improves the response against B16F10 cells. C57BL/6 mice were pre-treated with intraperitoneal (i.p) injection of OUA (0.56 mg/Kg) for three consecutive days. On the 4^th day, 10⁶ B16F10 cells or vehicle were i.p. injected. Animals were euthanized on days 4^th and 21^st for organs removal and subsequent lymphocyte analyses by flow cytometry. In vivo ouabain-treatment reduced regulatory T cells in the spleen in both melanoma and non-melanoma groups. Ouabain preserved the number and percentage of B lymphocytes in peripheral organs of melanoma-injected mice. Melanoma-injected mice pre-treated with OUA also survive longer. Our findings contribute to a better understanding of OUA immunological effects in a melanoma model.     

Immunoregulation through membrane proteins modified by reducing conditions induced by immune reactions

Selected disulfide bonds in membrane proteins are labile and are thus susceptible to changes in redox potential and/or the presence of thiol isomerase enzymes. Modification of these disulfide bonds can lead to conformational changes of the protein that in turn may alter protein activity and function. This occurs in the entry of several enveloped viruses into their host cells, e.g. HIV, hepatitis C virus and Newcastle disease virus. Labile disulfide bonds are also important in platelet activation, cytokine signalling and in a variety of diseases including cancer and arthritis. In this review we will concentrate on recent advances in understanding the conditions that lead to disulfide bond reduction in membrane proteins and their effects in regulating immune function.     

泛素编辑蛋白A20对呼吸机相关性肺炎患者单核细胞活性的影响

目的观察并分析泛素编辑蛋白A20对呼吸机相关性肺炎(ventilator associated pneumonia,VAP)患者单核细胞活性的影响。方法入选2019年2月至9月在郑州大学第一附属医院诊断为VAP的患者24例(VAP组)和健康对照12例(对照组)。分离VAP组外周血单个核细胞(peripheral blood mononuclear cells,PBMCs)、感染部位和非感染部位的支气管肺泡灌洗液(bronchial alveolar lavage fluid,BALF)及对照组PBMCs,检测CD14⁺单核细胞中A20水平。纯化VAP患者CD14⁺单核细胞和CD4⁺T细胞,使用A20 siRNA转染CD14⁺单核细胞。转染的CD14⁺单核细胞与自体CD4⁺T细胞直接/间接接触共培养,检测CD4⁺T细胞分泌干扰素-γ(interferon-γ,IFN-γ)和白细胞介素-17(interleukin-17,IL-17)水平。转染的CD14⁺单核与NCI-H889细胞直接/间接共培养,检测细胞毒性、分泌细胞因子、颗粒酶B水平及肿瘤坏死因子相关凋亡诱导配体(tumor necrosis factor-related apoptosis inducing ligand,TRAIL)、FasL配体(Fas ligand,FasL)水平。组间比较采用成组t检验或SNK-q检验。结果VAP组外周血CD14⁺A20⁺细胞比例高于对照组[(62.61±15.33)%vs.(47.13±11.82),P<0.05],A20平均荧光强度(mean fluorescence intensity,MFI)亦高于对照组[(227.9±64.18)vs.(178.2±58.62),P<0.05]。VAP组感染部位BALF中的CD14⁺A20⁺细胞比例高于未感染部位[(66.14±19.62)%vs.(52.52±13.71)%,P<0.05],A20 MFI亦高于未感染部位[(268.0±72.56)vs.(197.4±60.01),P<0.05]。A20 siRNA转染的VAP患者外周血和BALF中的CD14⁺单核细胞与自体CD4⁺T细胞直接接触共培养后,CD4⁺T细胞分泌IFN-γ和IL-17的细胞比例均高于未转染和siRNA转染(P<0.05),但间接接触共培养中,CD4⁺IFN-γ⁺和CD4⁺IL-17⁺细胞比例在未转染、对照siRNA转染和A20 siRNA转染中的差异无统计学意义(P>0.05)。A20 siRNA转染的VAP患者外周血和BALF中的CD14⁺单核细胞与NCI-H889细胞直接/间接接触共培养后,靶细胞死亡比例均高于未转染和siRNA转染(P<0.05),肿瘤坏死因子-α、IL-6、颗粒酶B水平及TRAIL MFI亦高于未转染和siRNA转染(P<0.05),但靶细胞死亡比例在直接接触和间接接触共培养之间的差异无统计学意义(P>0.05)。结论VAP患者单核细胞中A20水平升高,可能发挥抑制单核细胞活性的作用.     

抗血小板药物在脓毒症治疗中的应用

对于脓毒症的医疗投入逐年增加,但脓毒症的病死率却居高不下。目前研究已发现,脓毒症是炎症反应过度和凝血功能紊乱共同导致的,而血小板在其中起着重要作用。血小板形成的微血栓可加重器官功能障碍,甚至继发弥散性血管内凝血,还可加重炎症反应。如能在监测血小板功能情况下,适时地予以抗血小板治疗以减轻脓毒症对机体的损害,同时又不增加出血风险,这或将成脓毒症治疗新的方向。抗血小板药物为临床常用药物,且价格低廉,已在心脑血管疾病中广泛应用,但在脓毒症的治疗中报道较少。本文就抗血小板药物在脓毒症治疗中的可行性作一综述。     

白细胞介素-21在疾病中作用的研究进展

白细胞介素-21(IL-21)是一种新近发现的细胞因子,具有广泛生物学活性,能够调节B细胞的分化及免疫球蛋白类别转换,促进T细胞、NK细胞的增殖、分化,提高NK细胞杀伤活性,是多种自身免疫性疾病、感染性疾病、变态反应性疾病和肿瘤的重要致病因素,在疾病的发生发展中举足轻重,具有潜在临床研究价值,可能成为多种疾病治疗的新靶标.作为新的免疫系统调节因子,IL-21在免疫性疾病中的作用越来越受到关注,已成为近年来研究的热点.     

Human mesenchymal stromal cells modulate T‐cell responses through TNF‐α‐mediated activation of NF‐κB

Although mesenchymal stromal cells (MSCs) possess the capacity to modulate immune responses, little is known about the mechanisms that underpin these processes. In this study, we show that immunosupression is mediated by activation of nuclear factor kappa B (NF‐κB) in human MSCs. This pathway is activated by TNF‐α that is generated following TCR stimulation of T cells. Inhibition of NF‐κB through silencing of IκB kinase β or the TNF‐α receptor abolishes the immunosuppressive capacity of MSCs. Our data also indicate that MSC‐associated NF‐κB activation primarily leads to inhibition of T‐cell proliferation with little effect on expression of the activation markers CD69 and CD25. Thus, our data support the hypothesis that the TNF‐α/NF‐κB signalling pathway is required for the initial priming of immunosuppressive function in human MSCs. Interestingly, drugs that interfere with NF‐κB activation significantly antagonise the immunoregulatory effect of MSCs, which could have important implications for immunosuppression regimens in the clinic.     

非囊性纤维化性支气管扩张症的免疫调节机制

支气管扩张症是慢性炎症性支气管疾病的一种,病理上表现为一个或多个支气管的永久性扩张。非囊性纤维化性支气管扩张症的发病往往与反复感染、免疫缺陷或自身免疫性疾病相关,也有相当一部分呈特发性。细菌定植、气道炎症和气道结构损伤这样一个恶性循环导致了支气管扩张症的发生,其中气道炎症承前启后,是整个恶性循环的关键,因此研究气道炎症的免疫调节机制对理解其发病机理具有重要意义,并可指导支气管扩张症的药物研发。本文着重讨论了与支气管扩张症的发病密切相关的细胞与分子免疫调节机理,并阐述了细菌慢性定植的机理,还结合免疫调节讨论了支气管扩张症的新药研发。