丙泊酚麻醉对老龄大鼠认知功能和海马神经元γ-氨基丁酸A受体表达的影响

目的观察丙泊酚麻醉对老龄大鼠认知功能及海马神经元γ-氨基丁酸A(GABA)受体表达的影响。方法50只SD老年大鼠随机分为丙泊酚组和对照组,每组25只。丙泊酚组大鼠腹腔注射1%丙泊酚中/长链脂肪乳注射液6 mL/kg,对照组腹腔注射等体积的生理盐水。麻醉后1 d进行Morris水迷宫实验,分别采用HE染色和尼氏体染色观察海马区神经细胞及尼氏体(Nissl体)形态学变化,Western Blot检测GABA蛋白量表达。结果麻醉后,2组大鼠肛温、心率、呼吸频率、血氧饱和度比较,差异均无统计学意义(P>0.05)。随着实验时间的延长,2组大鼠逃逸潜伏期、总里程数逐渐减小,丙泊酚组大鼠各时间点逃逸潜伏期、总里程均高于对照组,差异有统计学意义(P<0.05)。丙泊酚组大鼠穿越平台区域次数、时间小于、短于对照组,差异有统计学意义(P<0.05)。对照组海马区Nissl体存在于细胞浆及树突,染色较深,神经细胞排列整齐,形态规则;丙泊酚组Nissl体消失,神经细胞数量减少,细胞核破裂、丢失。丙泊酚组大鼠海马GABA蛋白表达量低于对照组,差异有统计学意义(P<0.05)。结论丙泊酚对大鼠认知功能有影响,并与海马区GABA的表达相关。     

单孔胸腔镜下肺癌术后胸腔引流时间的影响因素分析北大核心

目的:探讨单孔胸腔镜下肺癌手术术后胸腔引流时间的影响因素。方法:本研究采用回顾性分析方法,回顾我院2018年01月至2019年12月原发性肺癌患者经单孔胸腔镜手术治疗的病例199例。按照术后胸腔引流时间分为两组,Ⅰ组(术后胸腔引流时间<5天)和Ⅱ组(术后胸腔引流时间≥5天)。对于影响术后胸腔引流时间的可能因素在两组间先采用单因素分析的方法筛选,再将筛选出来的对术后胸腔引流时间可能有意义的影响因素进行二项Logistic多因素回归分析。结果:经单因素分析及二项Logistic多因素回归分析结果显示:年龄≥60岁、手术部位、肺段切除术、胸膜粘连、手术时间≥180 min、术后早期下床活动是术后胸腔引流时间的独立影响因素(P<0.05)。结论:对于具有多个延长术后胸腔引流时间的独立影响因素的患者,应制定个体化管理方案,尽可能减少术后胸腔引流时间,减少住院天数,加快患者康复。     

γ-干扰素对大鼠胚胎基底前脑及隔区核团胆碱能神经元分化的影响

为了研究γ-干扰素(IFNγ)对大鼠胚胎基底前脑及隔区核团胆碱能神经元分化的作用,采用免疫组织化学方法对胆碱能神经元的特异性标记酶-胆碱乙酰基转移酶(ChAT)进行染色,ChAT阳性细胞的数量反映了胆碱能神经元的数量,并用14C-乙酰CoA作底物来检测ChAT活性。结果显示,IFNγ处理过的实验组,ChAT阳性细胞数量显著增加,ChAT活性也增加,这种增加被大鼠抗小鼠IFNγ单克隆抗体(Ab-IFNγ)完全拮抗。采用流式细胞术对细胞周期进行分析,细胞周期及细胞百分率无明显改变。用MAP2标记神经细胞,神经细胞数基本未增加。以上结果提示:IFNγ不能促进基底前脑和隔区神经元增殖,胆碱能神经元表达增加不是因为神经元数目增加而是分化的结果。     

巨细胞病毒肝炎患儿血清细胞因子水平测定及其临床意义

目的　研究巨细胞病毒 (CMV)肝炎患儿血清干扰素 α(IFN α)、白细胞介素 8(IL 8)和肿瘤坏死因子 α(TNF α)水平的变化及其临床意义。方法　应用ELISA法检测 35例CMV肝炎患儿血清中上述三种细胞因子的含量 ,并对其两两之间进行了相关性分析。结果　CMV肝炎组患儿IFN α、IL 8、TNF α的含量分别为 (770 .3± 2 0 5 .4 )ng/L、(41.9± 2 2 .5 )ng/L和 (10 33.2± 388.5 )ng/L ,非常显著高于正常对照组 (P <0 .0 1)。相关性研究发现IFN α与TNF α呈显著正相关 (r =0 .35 6 ,P <0 .0 5 )。结论　血清细胞因子明显增高与CMV肝炎的病理变化和病损程度有着密切的联系     

肝癌组织辅助性T细胞-2细胞因子强势分泌研究

目的　探讨人肝癌组织中辅助性T细胞亚群 (Th1/Th2 )细胞因子表达模式。方法　收集我科手术切除肝癌组织标本 15例 ,肝良性疾病或肝硬化门静脉高压手术患者肝组织标本 15例作为对照 ,β 肌动蛋白 (β actin)作为参照 ,采用半定量逆转录 聚合酶联反应 (RT PCR)方法检测人肝癌组织中γ 干扰素 (IFN γ)和白细胞介素 4(IL 4)mRNA的表达。结果　人肝癌组织中IFN γmRNA表达 (相对数 :1.18± 0 .3 1)比对照组肝组织中IFN γmRNA表达弱 (相对数 :1.86±0 .5 0 ) ,而IL 4mRNA表达 (相对数 :1.73± 0 .5 1)比对照组强 (相对数 :0 .94± 0 .41,P <0 .0 5 )。结论　人肝癌组织中Th1类细胞因子表达弱 ,Th2类细胞因子表达强 ,呈现Th2细胞因子表达模式 ,肝癌组织局部微环境处于免疫抑制状态 ,肿瘤细胞易发生免疫逃逸     

干扰素病毒唑联合治疗慢性丙型肝炎疗效及干扰素抗体的影响

目的 :研究干扰素与病毒唑联合治疗慢性丙型肝炎疗效及干扰素抗体的影响。方法 :观察组 2 0例采用干扰素 α2b 3MvTiwIH +病毒唑 10 0 0mgQdpo连用 2 4周 ;对照组 3 2例采用干扰素 α2b 3MvTiwiH连用 2 4周。停药后观察 2 4周比较疗效并检测干扰抗体。结果 :观察组完全应答率为 5 0 % ,明显高于对照组 18.7% ;复发率为 2 5 .0 %低于对照组 5 6.3 % (P <0 .0 1)。无反应率均为 2 5 .0 %。且复发与干扰素抗体尤其是中和抗体有关。结论 :观察组疗效优于对照组 ,复发与干扰素抗体尤其是中和抗体有关。     

Immunoglobulin mimicry by Hepatitis C Virus envelope protein E2

Hepatitis C virus (HCV) establishes persistent infection in the majority of infected individuals. The currently accepted hypothesis of immune evasion by antigenic variation in hypervariable region 1 (HVR1) of glycoprotein E2 does not however, explain the lack of subsequent immune recognition. Here, we show that the N-terminal region of E2 is antigenically and structurally similar to human immunoglobulin (Ig) variable domains. E2 is recognized by anti-human IgG antibodies and also possesses common amino acid (aa) sequence features of the conserved v-gene framework regions of human Ig light chains in particular but also heavy chains and T cell receptors. Using a position specific scoring system, the degree of similarity of HVR1 to Ig types correlated with immune escape and persistence in humans and experimentally infected chimpanzees. We propose a unique role for threshold levels of Ig molecular mimicry in HCV biology that not only advances our concept of viral immune escape and persistent infection but also provides insight into host-dependent disease patterns.     

Preservation and redirection of HPV16E7-specific T cell receptors for immunotherapy of cervical cancer

Human papilloma virus (HPV) type 16 infections of the genital tract are associated with the development of cervical cancer (CxCa) in women. HPV16-derived oncoproteins E6 and E7 are expressed constitutively in these lesions and might therefore be attractive candidates for T-cell-mediated adoptive immunotherapy. However, the low precursor frequency of HPV16E7-specific T cells in patients and healthy donors hampers routine isolation of these cells for adoptive transfer. To overcome this problem, we have isolated T cell receptor (TCR) genes from four different HPV16E7-specific healthy donor and patient-derived human cytotoxic T lymphocyte (CTL) clones. We examined whether genetic engineering of peripheral blood-derived CD8+ T cells in order to express HPV16E711-20-specific TCRs is feasible for adoptive transfer purposes. Reporter cells (Jurkat/MA) carrying a transgenic TCR were shown to bind relevant but not irrelevant tetramers. Moreover, these TCR-transgenic Jurkat/MA cells showed reactivity towards relevant target cells, indicating proper functional activity of the TCRs isolated from already available T cell clones. We next introduced an HPV16E711-20-specific TCR into blood-derived, CD8+ recipient T cells. Transgenic CTL clones stained positive for tetramers presenting the relevant HPV16E711-20 epitope and biological activity of the TCR in transduced CTL was confirmed by lytic activity and by interferon (IFN)-gamma secretion upon antigen-specific stimulation. Importantly, we show recognition of the endogenously processed and HLA-A2 presented HPV16E711-20 CTL epitope by A9-TCR-transgenic T cells. Collectively, our data indicate that HPV16E7 TCR gene transfer is feasible as an alternative strategy to generate human HPV16E7-specific T cells for the treatment of patients suffering from cervical cancer and other HPV16-induced malignancies.     

Single-Cell RNA Sequencing of Tumor-Infiltrating NK Cells Reveals that Inhibition of Transcription Factor HIF-1α Unleashes NK Cell Activity

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