肠疗与贝飞达合用治疗急性黄疸型肝炎的研究

目的 对90例急性黄疸型肝炎患者分别测定应用肠疗和贝飞达治疗前、后肠道菌群数量和红细胞粘附率、红细胞CR1分子数量及临床疗效评价指标,并进行比较。方法 将患者随机分成常规治疗、常规治疗加肠疗、常规治疗加肠疗与贝飞达3个治疗组（各30例）。分析患者治疗前后血液生化指标和肠道菌群数量及红细胞粘附率、红细胞CR1分子数量,并观察临床症状的改善情况。结果 急性黄疸型肝炎患者存在肠道菌群失调,红细胞粘附肿瘤功能及红细胞CR1分子数量明显下降（P〈0．01）;应用微生态调节剂组患者的肝功能恢复程度及临床症状的改善好于常规治疗组和常规治疗加肠疗组,差异有显著性（P〈0．01）。结论 结肠治疗机治疗联合微生态调节剂贝飞达可以有效改善急性黄疸型肝炎患者肠道菌群失调,提高患者红细胞粘附率及红细胞CR1分子数量,提高临床治疗有效率。     

甘氨双唑钠联合螺旋藻对原发性晚期宫颈癌患者血清TPS，sMICA，HIF-1α及Her-2水平的影响

目的:研究甘氨双唑钠联合螺旋藻胶囊对原发性晚期宫颈癌患者血清肿瘤标志物、多肽特异性抗原(TPS)、可溶性人类MHC-1类分子链相关基因A蛋白(s MICA)、缺氧诱导因子-1α(HIF-1α)及人表皮生长因子受体(Her-2)水平的影响。方法:选取2014年5月至2015年4月本院收治的88例原发性晚期宫颈癌患者,根据随机数字法分为观察组和对照组,44例每组。对照组采取放化疗,观察组在对照组基础上使用甘氨双唑钠联合螺旋藻胶囊。分析两组患者临床疗效和毒副反应,比较两组患者治疗前后免疫功能、血清肿瘤标志物、TPS、s MICA、HIF-1α及Her-2水平变化。结果:观察组总的临床有效率明显高于对照组(P0.05)。治疗后,两组患者SCCA、CEA、TA-4水平较治疗前显著降低(P0.05),和对照组相比,观察组的SCCA、CEA、TA-4水平较低(P0.05)。治疗后,两组患者TPS、s MICA、HIF-1α及Her-2水平和治疗前相比明显降低(P0.05),和对照组相比,观察组的TPS、s MICA、HIF-1α及Her-2水平较低(P0.05)。治疗后,两组患者CD3~+、CD4~+、CD4~+/CD8~+水平较治疗前显著升高(P0.05),CD8~+水平显著低于治疗前(P0.05),和对照组相比,观察组的CD3~+、CD4~+、CD4~+/CD8~+水平较高(P0.05),CD8~+水平较低(P0.05)。观察组口腔黏膜炎、贫血、腹泻、恶心呕吐、血小板减少、白细胞降低毒副反应率显著低于对照组(P0.05)。结论:甘氨双唑钠联合螺旋藻胶囊能有效降低原发性宫颈癌患者血清肿瘤标志物、TPS、s MICA、HIF-1α及Her-2水平,对患者免疫功能具有明显改善作用,能降低毒副反应率,临床疗效良好。     

重组人促红细胞生成素对血液透析患者营养状况和免疫功能的影响

目的:研究重组人促红细胞生成素对血液透析患者营养状态和免疫功能的影响。方法:选取2015年8月至2016年4月在我院进行维持性血液透析的患者共139名,随机分为对照组和观察组。对照组患者接受常规铁剂、叶酸等辅助治疗;观察组患者在常规治疗的基础上加用重组人促红细胞生成素。比较两组患者治疗前后血红蛋白、红细胞压积、营养状况(前白蛋白和转铁蛋白)以及免疫功能(CD4~+细胞、CD8~+细胞、CD4~+/CD8~+细胞和免疫球蛋白)等指标。结果:两组患者治疗前血红蛋白、红细胞压积、营养状况指标和免疫功能指标比较均没有统计学差异(P0.05)。治疗12周后,两组患者治疗后的血红蛋白、红细胞压积、前白蛋白、转铁蛋白均较治疗前显著升高(P0.05),且观察组患者以上指标较对照组升高更为明显(P0.05)。对照组患者治疗后的CD4~+细胞比例较治疗前明显升高(P0.05),但CD8~+细胞和CD4~+/CD8~+细胞比例没有显著变化(P0.05),而观察组治疗后这三类细胞的比例均较治疗前明显升高(P0.05)。观察组治疗后IgA、IgM和IgG浓度均较治疗前显著提升(P0.05),而对照组只有IgA和IgM浓度在治疗后有明显提高(P0.05),但仍显著低于观察组(P0.05)。结论:重组人促红细胞生成素能有效纠正血液透析患者的贫血情况,改善其营养状况并提高其免疫功能。     

正清风痛宁片联合塞来昔布对类风湿关节炎患者疾病活动指标、炎症因子及红细胞免疫功能的影响

目的:探讨正清风痛宁片联合塞来昔布对类风湿关节炎(RA)患者疾病活动指标、炎症因子及红细胞免疫功能的影响。方法:选取2016年8月～2019年10月我院接收的117例RA患者。根据随机数字表法分为研究组(n=59)、对照组(n=58)。对照组予以塞来昔布治疗,研究组在对照组的基础上联合正清风痛宁片治疗,两组均治疗1个月。统计两组治疗1个月后的临床疗效。比较两组治疗前、治疗1个月后的疾病活动指标[类风湿因子(RF)、C反应蛋白(CRP)、血沉(ESR)],红细胞免疫功能指标CR1、CD59以及炎症因子指标[肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)以及白介素-6(IL-6)],记录两组治疗期间不良反应情况。结果:研究组治疗1个月后的总有效率为89.83%(53/59),高于对照组的72.41%(42/58)(P0.05)。两组不良反应发生率对比无差异(P0.05)。两组治疗1个月后RF、CRP、ESR、TNF-α、IL-1β以及IL-6水平均较治疗前下降,且研究组低于对照组(P0.05)。两组治疗1个月后CR1、CD59均较治疗前升高,且研究组高于对照组(P0.05)。结论:正清风痛宁片联合塞来昔布治疗RA患者,疗效显著,可有效降低患者疾病活动指标、炎症因子水平,提高红细胞免疫功能,且不增加不良反应发生率。     

采用熔点曲线法研究乙肝病毒准种与拉米夫定临床耐药相关性

为了研究乙型肝炎病毒(HBV)准种与拉米夫定耐药的关系以指导临床用药,随机选取拉米夫定治疗后发生YMDD变异的慢性乙型肝炎(CHB)患者30例,以及停用拉米夫定后发生病毒反弹的CHB患者30例作为研究对象,同时以未经拉米夫定治疗的CHB患者30例为对照,采用聚合酶链反应(PCR)扩增这些病人体内HBV的P区,再用熔点曲线法分析3组患者体内的HBV准种情况。另外,采用相同方法对HBV C区、S区准种也进行了对比。结果显示,病毒变异组患者体内HBV P区准种数量为2.50±0.86个,病毒反弹组为5.30±0.95个,未治疗组为8.37±0.93个,3组间准种数量两两比较均有显著性差异(P<0.05)。HBV C区病毒变异组准种数量为6.10±1.86个,病毒反弹组为6.37±1.81个,未治疗组为6.33±1.64个,3组准种数量无显著性差异(P>0.05)。HBV S区病毒变异组准种数量为5.23±1.85个,病毒反弹组为6.17±1.93个,未治疗组为5.77±2.11个,3组准种数量无显著性差异(P>0.05)。HBV P区熔点曲线图显示,病毒变异组优势病毒群的熔点与病毒反弹组和未治疗组相比,已发生明显的偏移,而在HBV C区和S区熔点曲线图中,3组的波峰数和优势病毒群的熔点均没有明显变化。可见,在拉米夫定的作用下HBV P区准种数量减少,准种的性质也发生变化,发生变异后劣势耐药病毒株变为优势病毒株易被检测到。拉米夫定对HBV C区、S区作用不明显。     

贞芪扶正胶囊联合化疗对中晚期宫颈癌患者的疗效及免疫功能影响

目的:探讨贞芪扶正胶囊联合化疗对中晚期宫颈癌患者的疗效及免疫功能影响。方法:选取60例中晚期宫颈癌患者,按住院单双号分为两组,对照组(29例)采用TP方案化疗,共计2个疗程;观察组(31例)给予贞芪扶正胶囊联合TP方案化疗,共计2个疗程。通过观察并记录患者治疗后疗效,1年内局部复发率,远处转移率,治疗前后免疫功能变化及化疗期间不良反应情况。结果:2个疗程结束后观察组患者有效率明显高于对照组(P0.05);治疗后1年内,观察组与对照组患者在肿瘤局部复发率和远处转移率上相比没有明显差异(P0.05);治疗后观察组患者CD4~+T细胞、CD4~+/CD8~+、NK细胞水平明显升高且高于同期对照组患者(P0.05),CD8~+T细胞水平治疗前后无明显变化;治疗后对照组患者CD4~+T细胞、CD4~+/CD8~+水平明显下降(P0.05),CD8~+T细胞、NK细胞水平治疗前后无明显变化;化疗期间两组患者在恶心呕吐、肝功能损伤发生率上相比,差异没有统计学意义(P0.05),白细胞减少、血细胞下降在观察组的发生率明显低于对照组(P0.05)。结论:贞芪扶正胶囊联合化疗对中晚期宫颈癌患者具有较好的治疗效果,能提高患者免疫功能,减小不良反应,具有一定的临床应用价值。     

百令胶囊联合信必可对中重度稳定期慢性阻塞性肺疾病患者肺功能及免疫功能的影响

目的:探讨百令胶囊联合信必可对中重度稳定期慢性阻塞性肺疾病(COPD)患者肺功能及免疫功能的影响,为临床用药提供依据。方法:选取我院于2015年8月至2017年1月收治的104例COPD患者作为研究对象。采用随机数字表法将其分为单药组与联合组各52例。单药组患者单独给予信必可治疗及常规健康教育,联合组患者在单药组的基础上联用百令胶囊治疗。治疗前及治疗12周后对所有患者的用力肺活量(FVC)、第1秒用力呼气容积(FEV1)及两者之比(FEV1/FVC)进行测定,同时测定患者CD3~+,CD4~+T细胞,并计算CD4~+/CD8~+比值。观察并比较两组患者的临床疗效。结果:治疗12周后,两组患者FVC、FEV1、FEV1/FVC均明显升高(均P0.05),且与单药组比较,联合组患者FVC、FEV1、FEV1/FVC均明显更高(均P0.05)。治疗12周后,两组患者CD3~+、CD4~+及CD4~+/CD8~+均明显升高(均P0.05),且与单药组比较,联合组患者CD3~+CD4~+及CD4~+/CD8~+均明显更高(均P0.05)。联合组总有效率为86.54%,明显高于单药组的67.31%(P0.05)。结论:百令胶囊联合信必可治疗中重度稳定期COPD患者疗效确切,能有效改善患者肺功能并提高免疫功能,值得在临床上推广。     

营养支持联合免疫调节治疗老年慢阻肺急性发作期的临床效果

目的：观察老年慢性阻塞性肺疾病（COPD）急性发作期行营养支持联合免疫调节治疗的临床效果。方法：选取济宁市第一人民医院 2016年1月-2018年1月收治的COPD急性发作期患者200例，随机分为观察组108例和对照组92例，对照组给予营养支持治疗，观察组在对照组治疗基础上行免疫支持治疗，观察两组治疗后的临床效果。结果：治疗后，观察组临床治疗总有效率明显高于对照组（χ2=8.61，P＜0.01），外周血管淋巴细胞（TLC）、IgA以及T淋巴细胞（CD4+、CD8+、CD4+/CD8+）等免疫指标明显优于对照组（P＜0.05或P＜0.01），体重、TP、ALB等营养指标和PaO2、SaO2、PaCO2等血气分析指标也明显优于对照组（P＜0.05或P＜0.01）。结论：对老年COPD急性发作期患者在营养支持基础上给予免疫调节治疗能明显改善患者营养水平和免疫功能，增加肺通气功能，提高临床治疗效果。     

低分子肝素与小剂量阿司匹林联合可有效治疗复发性流产

为了弄清低分子肝素、小剂量阿司匹林在治疗复发性流产患者的临床疗效,本研究选取2012年6月~2015年1月在我院治疗的138例复发性流产患者为研究对象,采用随机数字表法分为肝素组、阿司匹林组、联合组各46例,分别给予低分子肝素、小剂量阿司匹林、低分子肝素联合小剂量阿司匹林进行临床治疗。试图通过比较3组治疗前后激素水平、凝血功能、免疫功能、妊娠结局阐明治疗复发性流产患者的临床疗效。结果表明激素水平:联合组雌二醇(E2)、孕酮(P)血清绒毛膜促性腺激素(β-HCG)含量明显高于肝素组、阿司匹林组(t=2.998~5.176,p0.05);凝血功能:联合组凝血酶时间(TT)明显高于肝素组、阿司匹林组,D-二聚体(D-D)明显低于肝素组、阿司匹林组(t=3.708~3.643,p0.05);免疫功能:联合组CD4+、CD4/CD8明显低于肝素组、阿司匹林组(t=2.821~6.998,p0.05);妊娠结局:联合组患者活产率明显高于肝素组、阿司匹林组(84.78%vs 60.87%vs 58.70%),(x~2=6.646~7.720,p0.05)。显然,本研究结果表明:低分子肝素联合小剂量阿司匹林对于保持复发性流产患者的情况稳定以及其激素水平的提高具有显著的意义,抑制血栓前状态,增强母体对胚胎的免疫耐受能力,改善妊娠结局,安全有效,值得临床应用推广。     

腹泻小儿便中双歧杆菌含量变化和红细胞免疫功能关系的探讨

目的：研究腹泻小儿便中双歧杆菌含量变化与红细胞免疫的关系。方法：对42例腹泻小儿和38例正常小儿进行了粪便双歧杆菌含量、红细胞CR1数量及红细胞自然粘附肿瘤花环率（NTRR）的测定。结果：与正常小儿相比,腹泻小儿粪便中双歧杆菌含量明显下降,红细胞CR1数量无明显改变,NTRR明显下降。结论：小儿肠道内双歧杆菌含量与其红细胞CR1免疫活性有相关关系。     

恩替卡韦对CHB患者外周血T淋巴细胞PD-1水平及

摘要：目的 探讨恩替卡韦对慢性乙型肝炎（CHB）患者外周血T淋巴细胞程序性死亡受体1（PD-1）水平及肝功能的影响。方法 将128例CHB患者随机分为观察组及对照组各64例,对照组患者给予拉米夫定治疗,观察组在对照组基础上给予恩替卡韦治疗。分别于治疗前、治疗后1个月、3个月、6个月、12个月抽取静脉血5 mL,采用荧光定量PCR检测患者血清HBV DNA载量,流式细胞术检测T淋巴细胞PD-1表达水平,全自动化生化分析仪测定患者血清谷草转氨酶（ALT）水平。结果 两组组患者治疗1个月、3个月、6个月、12个月HBV DNA载量、ALT水平、CD4+T细胞PD-1、CD8+ T细胞PD-1水平均低于治疗前（P<0.05）。观察组治疗后1个月、3个月、6个月、12个月HBV DNA载量、ALT水平、CD4+ T细胞PD-1、CD8+ T细胞PD-1水平低于对照组（P<0.05）。结论 恩替卡韦能有效抑制CHB患者外周血CD4+、CD8+ T细胞表面PD-1表达水平,进而抑制HBV DNA复制,改善患者肝功能。     

Dynamic changes of hepatitis B virus polymerase gene including YMDD motif in lamivudine-treated patients with chronic hepatitis B

The mutation of YMDD motif of hepatitis B virus (HBV) polymerase gene is the most frequent cause in HBV resistant to lamivudine. The aim of the study was to investigate variation features of HBV polymerase gene in chronic hepatitis B (CHB) patients before and after lamivudine treatment. From the serum samples of five CHB patients before and after 12 months of lamivudine treatment, HBV polymerase gene was amplificated and positive DNA fragments were cloned into JM105 competent cell. Twenty positive clones of every sample were checked with mismatched polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and YMDD variants were sequenced. Among five patients after 12 months of lamivudine treatment, M552I mutations in two patients with HBV DNA rebounding and D553G mutation in one non-responder were detected except two patients with negative HBV DNA consecutively. In summary, D553G mutation is probably one of the reasons that caused non-responders during lamivudine treatment. The mutations of YMDD motif occurred after lamivudine treatment are caused by the induction of lamivudine.     

拉米夫定与IFNα-1b序贯治疗HBeAg阳性慢性乙肝患者临床疗效观察

目的：观察比较拉米夫定联合IFNα-1b的序贯疗法与拉米夫定,IFNα-1b的单药疗法在治疗HBeAg阳性的慢性乙型肝炎方面的疗效差异。方法：将98例HBeAg阳性慢乙肝患者随机分为序贯治疗组、拉米夫定治疗组和IFNα-1b治疗组。序贯治疗组33例,年龄37．85±7．70岁,男／女：18／15,首先使用拉米夫定（100mg—El一次口服疗程24周）,序贯使用IFNα-1b（60ug隔日一次皮下注射疗程28用1,在第20周至24同同时使用拉米夫定和IFNα-1b,总疗程48周;拉米夫定治疗组34例,年龄39．42＋6．88岁．男／女：20／14,仅口服拉米夫定,100mg一日一次口服,疗程48周;IFNα-1b治疗组31例,年龄35．71±6．14岁,男／女：14／17,仅皮下注射IFNα-1b,60ug隔日一次,疗程48周。治疗12周、24周、48周时检测肝功能、乙肝两对半、HBV—DNA等指标变化。结果：在治疗12周、24周时三组间肝功复常率、HBeAg阴转率无差异,序贯治疗组、拉米夫定组HBV·DNA阴转率优于IFNα-1b治疗组;实验疗程结束时序贯治疗组HBeAg阴转率、抗-HBe转换率及HBV—DNA阴转率显著高于其他两组,P〈0．05,但在HBV-DNA阴转率方面序贯治疗组与拉米夫定治疗组差异不显著。结论：拉米夫定和IFNα-1b序贯疗法在HBV—DNA阴转率、HBeAg阴转率和抗HBe转换率三方面的疗效优于拉米夫定、IFNα-1b单一用药。     

胸腹腔镜联合Ivor Lewis食管癌根治术对食管癌患者肺功能、红细胞免疫及应激反应的影响

目的:探讨胸腹腔镜联合Ivor Lewis食管癌根治术对食管癌患者红细胞免疫、肺功能及应激反应的影响。方法:选取2016年5月~2018年6月期间我院收治的食管癌患者150例。根据随机数字表法将患者分为A组(n=75)和B组(n=75),A组予以开胸Ivor Lewis食管癌根治术,B组予以胸腹腔镜联合Ivor Lewis食管癌根治术,比较两组围术期指标、肺功能、红细胞免疫、应激反应及并发症。结果:B组手术时间、住院时间短于A组,术中出血量少于A组(P<0.05);两组清扫淋巴结数目比较无差异(P>0.05)。两组术后1个月第1秒末用力呼气容积(FEV1)、用力呼吸肺活量(FVC)、FEV1/FVC均降低,但B组高于A组(P<0.05)。两组术后3d白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)均升高,但B组低于A组(P<0.05)。两组术后3d红细胞免疫复合物花环率(RBC-ICR)升高,但B组低于A组(P<0.05);红细胞C3b受体花环率(RBC-C3bRR)、肿瘤红细胞花环率(TRR)降低,但B组高于A组(P<0.05)。两组患者术后并发症发生率比较差异无统计学意义(P>0.05)。结论:胸腹腔镜联合Ivor Lewis食管癌根治术治疗食管癌患者,可有效改善围术期各项指标,减轻对机体肺功能、红细胞免疫及应激反应的影响,且不增加并发症发生率。     

Dehydroepiandrosterone protects the microcirculation of muscle flaps from ischemia-reperfusion injury by reducing the expression of adhesion molecules

Adhesion molecules contribute to ischemia-reperfusion injury by increasing the endothelial adhesion and extravasation of leukocytes. Scientific evidence suggests that presurgical treatment with dehydroepiandrosterone may protect the microvasculature against this damage, but the exact mechanism is not known. The purpose of this study was to investigate the effects of presurgical dehydroepiandrosterone treatment on microcirculatory hemodynamic parameters and the expression of adhesion molecules in a rat cremaster muscle flap model. Twenty male rats were randomly assigned to three experimental groups. In group I (n = 5), the muscle flaps did not receive presurgical treatment. In group II (n = 6), propylene glycol (30 mg/kg), the vehicle for dehydroepiandrosterone, was injected intravenously before ischemia was induced. In group III (n = 9), dehydroepiandrosterone (30 mg/kg) was injected intravenously before ischemia was induced. All flaps were subjected to 6 hours of ischemia and 90 minutes of reperfusion. Microcirculatory variables (functional capillary density, red blood cell velocity in the main flap arteriole, and numbers of rolling, sticking, and transmigrating leukocytes), blood levels of three adhesion molecules (L-selectin, Mac-1 integrin, and CD44), and the numbers of leukocytes expressing those molecules were analyzed. Analysis of the microcirculatory parameters revealed that dehydroepiandrosterone treatment before ischemia had significant preservative effects on the red blood cell velocity and functional capillary density 30 and 90 minutes after reperfusion, compared with the control and vehicle-treated groups. Leukocyte-endothelial cell interactions were also affected by dehydroepiandrosterone treatment, as reflected by significant decreases in the numbers of sticking and transmigrating leukocytes 30 and 90 minutes after reperfusion. In dehydroepiandrosterone-treated animals, leukocytes exhibited lower levels of expression of adhesion molecules after the onset of ischemia, compared with the control groups. In this study, intravenous dehydroepiandrosterone administration reduced the activation of leukocytes and improved red blood cell velocity and capillary perfusion in the muscle flap microcirculation during ischemia-reperfusion injury. This protective effect was most likely the result of delayed expression of Mac-1 integrin, L-selectin, and CD44 molecules on leukocytes.     

Therapy for oral squamous cell carcinoma by tegafur and streptococcal agent OK-432 in combination with radiotherapy: Association of the therapeutic effect with differentiation and apoptosis in the cancer cells

Twenty patients with oral squamous cell carcinoma having mainly stage II or III lesions without distant metastasis, were treated with tegafur and streptococcal agent, OK-432, in combination with radiotherapy. As a consequence, 16 cases among the treated 20 cases showed complete remission by this therapy alone. Especially, we have found that the squamous cell carcinoma arising in non-keratinizing oral epithelium rather than in keratinizing oral epithelium has better response to this therapy. Among the 16 cases with complete remission (CR) by the current therapy, 10 cases were histopathologically diagnosed as well-differentiated squamous cell carcinoma and six cases as moderately differentiated squamous cell carcinoma. When we examined immunohistochemically the expres-sion of various antigens such as proliferating cell nuclear antigen (PCNA), p53 and LeY or the presence of DNA fragmentation by nick-end labelling in the biopsy materials taken at the first visit to our clinic from 20 patients treated with the current therapy, the CR group showed a significantly increased LeY expres-sion level ( p< 0.05) and DNA fragmentation rate ( p< 0.05) as compared with the partial response (PR, n= 3) + no change (NC, n= 1) group. On the other hand, the CR group with respect to PCNA expression level was significantly decreased as compared with the PR + NC group ( p< 0.05). From these findings, it can be considered that the therapy for oral squamous cell carcinoma by UFT and OK-432 in combination with radiotherapy is very effective, which may be associated with differentiation or apoptosis in oral squamous carcinoma cells. In addition, we present the clinical findings and results of immunohistochemical staining for the biopsy materials obtained from four CR cases treated with the current therapeutic method.     

Restoration of TLR3-activated myeloid dendritic cell activity leads to improved natural killer cell function in chronic hepatitis B virus infection

There is increasing evidence that the function of NK cells in patients with chronic hepatitis B (CHB) infection is impaired. The underlying mechanism for the impaired NK cell function is still unknown. Since myeloid dendritic cells (mDC) are potent inducers of NK cells, we investigated the functional interaction of mDC and NK cells in CHB and the influence of antiviral therapy. Blood BDCA1(+) mDC and NK cells were isolated from 16 healthy controls or 39 CHB patients at baseline and during 6 months of antiviral therapy. After activation of mDC with poly(I · C) and gamma interferon (IFN-γ), mDC were cocultured with NK cells. Phenotype and function were analyzed in detail by flow cytometry and enzyme-linked immunosorbent assay. Our findings demonstrate that on poly(I · C)/IFN-γ-stimulated mDC from CHB patients, the expression of costimulatory molecules was enhanced, while cytokine production was reduced. In cocultures of poly(I · C)/IFN-γ-stimulated mDC and NK cells obtained from CHB patients, reduced mDC-induced NK cell activation (i.e., CD69 expression) and IFN-γ production compared to those in healthy individuals was observed. Antiviral therapy normalized mDC activity, since decreased expression of CD80 and CD86 on DC and of HLA-E on NK cells was observed, while poly(I · C)/IFN-γ-induced cytokine production by mDC was enhanced. In parallel, successful antiviral therapy resulted in improved mDC-induced NK cell activation and IFN-γ production. These data demonstrate that CHB patients display a diminished functional interaction between poly(I · C)/IFN-γ activated mDC and NK cells due to impaired mDC function, which can be partially restored by antiviral therapy. Enhancing this reciprocal interaction could reinforce the innate and thus the adaptive T cell response, and this may be an important step in achieving effective antiviral immunity.     

B7-H1 up-regulation on myeloid dendritic cells significantly suppresses T cell immune function in patients with chronic hepatitis B

Although dysfunctional dendritic cells contribute to inadequate adaptive immunity in chronic hepatitis B (CHB), underlying molecular mechanisms remain largely undefined. In this study, we examined B7-H1 expression on circulating myeloid dendritic cells (mDCs) in 46 CHB patients, 10 autoimmune hepatitis patients, and 10 healthy subjects as control. We found that B7-H1 expression is significantly up-regulated on circulating mDCs of CHB and autoimmune hepatitis patients compared with healthy individuals. The B7-H1 up-regulation was significantly correlated with an elevation of serum alanine aminotransaminase levels and plasma viral load. In addition, in vitro, both IFN-alpha and IFN-gamma could strongly stimulate mDCs to express B7-H1. More importantly, elevated B7-H1 expression is also closely associated with the suppression of T cell immune function. In vitro blockade of B7-H1 signaling could not only down-regulate IL-10 and up-regulate IL-12 production by mDCs, but also enhance mDC-mediated allostimulatory capacity and cytokine production of T cells. Blockade of B7-H1 signaling could improve hepatitis B c Ag-pulsed monocyte-derived DC-induced IFN-gamma production by autologous hepatitis B virus-specific T cells. These new findings suggested that chronic inflammation may contribute to B7-H1 up-regulation on mDCs in CHB patients, which potentially cause defective hepatitis B virus-specific T cell function and viral persistence. Our findings further support the notion that the blockade of B7-H1 may represent a novel therapeutic approach for this disease.     

拉米夫定联合胸腺肽A1 治疗慢性乙型肝炎的疗效观察

目的:探讨拉米夫定(LAM)联合胸腺肽α1(Tα1)治疗慢性乙型肝炎的长期疗效和安全性。方法:72例慢性乙肝患者(HBV-DNA和HBeAg均阳性),按1:1随机分配进入联合治疗组(LAM+Tα1组)和单用拉米夫定组(LAM组)。结果:治疗1年时LAM+Tα1组HBeAg血清转换率(44.4%,16/36例)明显高于LAM组(5.6%,2/36例),P<0.01。停药1年后,持续的HBeAg血清转换率分别为36.1%(13/36例)和8.3%(3/36例),P<0.01。治疗过程中及停药后,两组HBV-DNA水平均明显下降,但两组的HBV-DNA转阴率相仿。治疗后1年ALT复常率联合治疗组与拉米夫定组相似,分别为75%(27/36例)和66.7%(24/36例)、随访1年时ALT复常率联合治疗组明显高于拉米夫定组,分别为58.3%(21/36例)和16.7%(6/36例)。在治疗过程中,未发现严重的不良反应。结论:LAM联合Tα1治疗慢性乙肝,不良反应少,疗效优于单一LAM用药组。