干扰素对慢性乙型肝炎患者肝功能及肝纤维化的疗效

目的观察应用干扰素α1β治疗慢性乙型肝炎（乙肝）患者改善其肝纤维化情况的疗效。方法2007年1月～2009年8月期间我院门诊经病理确诊的慢性乙肝致肝纤维化患者67例,随机分为干扰素治疗组（35例）和对照组（32例）,两组均给予常规中药（扶正化淤胶囊）保肝降酶治疗,干扰素治疗组加用干扰素a1β（赛若金）40腭肌肉注射,隔日1次,疗程均为24周。观察两组患者症状、体征,肝功能指标如丙氨酸转氨酶（ALT）、胆红素（BIL）、白蛋白（ALB）和白蛋白／球蛋白比例（A／G）以及血清胆碱酯酶（ChE）、转化生长因子（TGF—β1）和透明质酸（HA）的含量。结果与对照组相比,干扰素治疗组肝功能显著好转。治疗组AⅡ为（58．8±26．4）U／L,高于对照组（129．6±36．9）U／L（P〈0．01）;治疗组BⅡ为（31．0±17．9）μmoL／L,低于对照组（49．3±19．6）μmol／L（P〈0．01）;治疗组ALB（40．5±6．6）g／L,高于对照组（32．1±6．1）g／L（P〈0．01）;白蛋白／球蛋白比例（A／G）对照组高于治疗组（P〈0．01）。肝纤维化指标也有显著改善,如血清ChE治疗组（3919±101）U／L、对照组（2289±191）U／L（P〈0．01）;TGF－β1治疗组（101±31）μg／L、对照组（144±19）μg／L（P〈0．01）;HA治疗组（91．6±36．2）μg／L、对照组（149．1±30．9）μg/L（P〈0．01）。治疗组患者腹胀及肝区疼痛有不同程度的缓解,脾肿大有较大程度的缓解。结论应用干扰素a1β治疗慢性乙肝导致的肝纤维化患者,可改善患者的临床症状、体征,促进肝功能在生化指标方面的恢复并缓解肝纤维化。     

经胸腔镜喷洒滑石粉及干扰素治疗恶性胸腔积液的疗效观察

目的 探讨经胸腔镜喷洒滑石粉及干扰素对恶性胸腔积液的治疗效果。方法 将临床确诊的恶性胸腔积液64例,病例随机分为两组：治疗组采用胸腔镜下喷洒滑石粉及干扰素,所有病例均不予全身化疗;对照组单用闭式引流。观察两组的临床疗效、生活质量及不良反应。结果 治疗组平均拨管时间较对照组缩短（P〈0．01）。治疗组排液量较对照组减少（P〈0．05）。完全缓解率治疗组为81．2％,对照组为60．0％,两组比较有显著差异性（P〈0．01）。但两组术后发热、胸痛等副作用的发生率无显著差异（P〉0．05）。结论 经胸腔镜喷洒滑石粉联合干扰素治疗恶性胸腔积液有具有创伤小,疗效好,见效快,不易复发,并发症少等优点。     

胸腺肽α1治疗慢性乙型肝炎的近期疗效观察

探讨胸腺肽α1（简称Tα1）治疗慢性乙型肝炎（CHB）的疗效。采用Tα1治疗CHB患者32例，同时用猪苓多治疗30例作为对照组，疗程均为3个。ALT及乙肝病毒标志物的变化为考核依据。治疗组ALT复常率、HB Agn HBVDNA转阴率分别为93．％，46．9％，50％，均显著高于对照组（P＜0．05）。提示Tα1治疗CHB病人具有显著的按期疗效。     

阿德福韦抗乙肝病毒感染治疗动力学模型

基于阿德福韦(Adefovir dipivoxil)与安慰剂治疗180余位HBeAg阴性的慢性乙型肝炎(CHB)患者国际联合研究的临床数据,以及Nowak等人提出的不带效应细胞的乙肝病毒(HBV)感染模型,提出了一个由两个系统组成的数学模型, 模型对CHB患者的阿德福韦治疗效果提供了一种可能的解释, 特别是可以解释为什么患者血浆中病毒数目在停止免疫治疗后会迅速反弹. 该模型对长期的疗效做出预测:血清HBV DNA接近中位数的患者需要延长治疗时间到5.6 a,以清除CHB患者体内的HBV. 本研究提示:将血清DNA小于500 copies·mL-1作为评价疗效的标准过于粗糙.     

重组人α-2a干扰素栓治疗宫颈糜烂疗效观察

目的：评价重组人α-2a干扰素栓治疗宫颈糜烂的疗效及安全性。方法：采用多中心、随机、双盲、基质平行对照试验，按病例接纳顺序随机表分治疗组120例、对照组90例，观察时间为6周。结果：重组人α-2a干扰素栓治疗宫颈糜烂痊愈率50．0％，总有效率98．3％，与对照组比较，有显著性差异（P〈O．05）。结论：重组人α-2a干扰素栓治疗宫颈糜烂有较好的临床疗效，使用方便安全。     

132例急性乙型肝炎患者HBV基因型分析

为检查本地区HBV感染者基因型，对132例本地区急性乙型肝炎患者血清中HBV、DNA通过PCR检测技术进行基因型分析，结果：C型101例（75．5％），B型15例（11．7％），BC混合型12例（8．7％），A型1例（0．9％），检测结果与KaoJ H、XinDing等报道基本相似．但在132例患者中，有3例未确定基因型，原因，有待进一步探讨．     

干扰素联合苦参治疗慢性乙型肝炎的疗效观察

目的：观察干扰素联合苦参素治疗慢性乙型肝炎的疗效。方法：干扰素组用α-2b干扰素300万IU，肌注，隔日一次，苦参素组用苦参素注射液600mg，肌注，每日一次，联合组用c-2b干扰素300万IU，肌注，隔日一次，同时用苦参素注射液600mg，肌注，隔日一次。以上三组均为16周为一个疗程。结果：肝功能复常幸、HBeAg转阴幸、HBeAb阳转车、HBVDNA转阴率和外周血WBC和PLT下降率干扰素组分别为82％、46．4％、39．2％、42．9％和28．6％；苦参素组80％、40％、33．3％、36．7％和0％；联合组90％、63．3％、56．7％、63．3％和3．3％。苦参素组的外周血WBC和PLT不仅无下降，反而有不同程度的升高。结论：干扰素联合苦参素治疗慢性乙型肝炎的疗效较为理想。     

HBeAg阴性慢性乙型肝炎病毒载量与肝损害的关系

目的: 探讨HBeAg阴性慢性乙型肝炎患者血清HBV DNA水平与肝组织损害的关系.方法:以HBeAg阳性慢性乙型肝炎病例为对照,回顾分析HBeAg阴性慢性乙型肝炎患者血清HBV DNA水平与丙氨酸转氨酶(ALT)水平、肝组织病理炎症分级之间的关系.结果:HBeAg阴性与阳性组HBV DNA平均含量分别为1.2×107拷贝/mL,8.2×107拷贝/mL(P=0.000).HBeAg阴性组HBV DNA水平与ALT水平呈正相关(rs=0.261,P=0.000).与HBeAg阳性组比较,HBeAg阴性组肝组织炎症分级较低(P=0.032).HBeAg阴性患者HBV DNA水平与肝组织炎症分级呈正相关(rs=0.371,P=0.009).结论:HBeAg阴性慢性乙型肝炎病毒载量较低,乙肝病毒载量与肝损害呈正相关.     

静脉注射丙种球蛋白辅助治疗23例重症传染性非典型肺炎

目的：评价静脉注射丙种球蛋白（IVIG）在辅助治疗重症传染性非典型肺炎中的临床价值。方法：应用MG治疗23例重症传染性非典型肺炎患者,同时选择常规治疗21例作为对照组,检测治疗前后血清球蛋白水平,比较两组间病死率及医院感染发生率。结果：对照组血清球蛋白随病情发展显著下降（t=9．153 P〈0．01）,治疗组血清球蛋白在治疗后略有上升,但差异没有显著性意义（t=1．611 P〉0．05）;两组间病死率及医院感染发生率的比较差异均无显著性（P〉0．10）。结论：MG不能降低重症传染性非典型肺炎患者病死率及医院感染发生率,因而不建议在重症传染性非典型肺炎中应用。     

镁缺乏对充血性心力衰竭的影响

目的：研究镁缺乏对充血性心力衰竭的影响。方法：回顾性分析了227例充血性心力衰竭患者（CHF）,其中137例加用硫酸镁治疗（Ⅰ组）,140例未加用硫酸镁治疗（Ⅱ组）。结果：Ⅰ组总有效率92．7％,显效率64．2％,均显著高于Ⅱ组（P＜0.01）。疗效出现时间显著短于Ⅱ组（P＜0．01）,并且死亡率显著低于Ⅱ组（P＜0．01）低钾、室性心律失常、洋地黄中毒等并发症也显著低于Ⅱ组（P＜0．01、P＜0．01,P＜0．01）。结论：在CHF患者的治疗中,应重视镁缺乏的影响,及时加用镁剂治疗,可能对提高CHF患者的生存率,减少室性心律失常,猝死等并发症的发生率,降低死亡率有重要意义。     

Enhancing cellular immune response to HBV M DNA vaccine in mice by codelivery of interleukin-18 recombinant

OBJECTIVE: To investigate the effect of interleukin-18 (IL-18) on immune response induced by plasmid encoding hepatitis B virus middle protein antigen and to explore new strategies for prophylactic and therapeutic HBV DNA vaccines. METHODS: BALB/c mice were immunized with pCMV-M alone or co-immunized with pcDNA3-18 and pCMV-M and then their sera were collected for analysing anti-HBsAg antibody by ELISA; splenocytes were isolated for detecting specific CTL response and cytokine assay in vitro. RESULTS: The anti-HBs antibody level of mice co-immunized with pcDNA3-18 and pCMV-M was slightly higher than that of mice immunized with pCMV-M alone, but there was not significantly different (P>0.05). Compared with mice injected with pCMV-M, the specific CTL cytotoxity activity of mice immunized with pcDNA3-18 and pCMV-M was significantly enhanced (P<0.05) and the level of IFN-Gamma in supernatant of splenocytes cul-tured with HBsAg in vitro was significantly elevated (P<0.05) while the level of IL-4 had no significant difference (P>0.05). CONCLUSION: The plasmid encoding IL-18 together with HBV M gene DNA vaccines may enhance specific TH1 cells and CTL cellular immune response induced in mice, so that IL-18 is a promising immune adjuvant.     

母婴配对血清中TT病毒的分子鉴定

为了解TT病毒（TTV）在我国母婴间传播的可能及分子病毒学依据，合成引物（引物1：5′－ACAGACAGAGGAGAAGGCAACATG－3′；引物2：5′－CTGGCATTTTACCATTTCCAAAGTT－3′；引物3；5′－GGCAACATGTTATGGATAGACTGG－3′），采用半套式聚合酶链反应（hemi-nested PCR）方法，检测了40对母、婴母对血清中的TTV DNA，并对TTV DNA均阳性的一对母婴配对血清中PCR产物进行测序和序列分析，结果发现：（1）在40例产妇血清中，有5例经半套式PCR检出了TTV DNA，检出率为12.5%；40例脐血中，检出TTV DNA阳性血清1例，阳性率为2.5%，脐血呈阳性的新生儿母亲静脉血中TTV DNA也为阳性。（2）母婴同时检出TTV DNA的血清PCR产物经测序后进行序列比对，二者病毒核苷酸序列的同源性为1005；与日本G2b型代表株核苷酸同源性为98.6%，属于G2b亚型，研究结果表明：TTV存在母婴传播途径，TTV可经胎盘垂直传播。     

拉米夫定治疗慢性乙型肝炎病人出现YMDD变异后继续长期应用的疗效观察

88例病人服用拉米夫定三年,共有51例出现YMDD变异.定期观察其中出现YMDD变异后继续长期应用拉米夫定的44例病人,观察项目包括临床表现、ALT、SB、乙型肝炎病毒血清学标志、HBV DNA及YNDD变异情况.48 周、104周和168周YMDD变异率分别为21.7%、48%和68.4%.44例继续用药病人按变异后ALT的变化分为三组:ALT值<1ULN(16例)、>1-5ULN(21例)和>5ULN(7例);HBV DNA中位值分别为0.88、200.93和537.70 mEq/mL;血清转换分别为7、1和1例.与无病毒变异组的血清转换率61.1%相比,变异后ALT正常组为43.8%(P>0.05),变异后ALT异常组为7.1%(P<0.01).因此,拉米夫定对大多数YMDD变异的慢性乙型肝炎病人仍有效,但必须在严密监测下使用.     

Construction of multivalent DNA vaccines forMycobacterium tuberculosis and its immunogenicity

The coding regions of Ag85B MPT-64, and ESAT-6 secreted proteins were cloned initially into the eukaryotic expression vector pJW4303, then transformed to E. coli Top 10 strain for plasmid DNA extraction and further analysis. Plasmids containing the right insertion were sequenced to confirm their identity. COS7 cells were transfected with a mixture containing serially diluted plasmid DNA encoding three secreted proteins and Lipofectin (Gibco). The supernatants and pellets prepared from various cell lines were run on SDS-PAGE gel and the expression of these proteins in COS7 cells were demonstrated by immunoblot using polyclonal or monoclonal antiserum of M.TBH37Rv. 21 days after first vaccination of C57BL-6 mice by all three recombinant eukaryotic expressing vectors, antibody titer for Ag85B reached 1∶3200. 21 days after second vaccination, the antibody titer reached 1∶102400. The highest antibody levels induced by multivalent vaccines after the second injection were equal to or even greater than the highest antibody levels of single DNA vaccine reported in literature after third injections. Antibody titer of MPT-64 was 1∶50 after the first injection and it reached 1∶200 after the second injection. No antigen-specific antibody against ESAT-6 was detected in sera harvested from immunized mice 21 days after both injections. Antigen-specific IFN-g level of Ag85B was 110 pg/mL while no antigen-specific IFN- g level of ESAT-6 and MPT-64 was detected even after third injections. To our knowledge, it is the first time that studies of polyvalent recombinant DNA vaccines against TB were carried out in C57BL-6 mice. Our results indicated that multiple DNA vaccines could be used to enhance protective responses against M.TB.     

拉米夫定治疗慢性乙型肝炎过程中HBV YMDD变异株的检测

目的观察拉米夫定治疗慢性乙型肝炎过程中,乙型肝炎病毒(HBV)发生 YMDD变异的情况;研究HBV YMDD变异的发生率同拉米夫定用药时间及用药前与血清HBV DNA水平的关系;观察拉米夫定治疗过程中,血清HBV DNA水平的变化.方法 80例慢性乙型肝炎病人被分为2组,1组为拉米夫定治疗组50例,另1组为对照组30例.采用实时PCR技术,并结合荧光探针技术,分别检测拉米夫定治疗组和对照组在用药期间的HBV YMDD变异发生率;采用荧光定量PCR技术检测治疗组在用药前及用药期间血清HBV DNA水平.结果治疗组在用药52周时的HBV YMDD变异发生率为24.0%,明显高于对照组用药52周的变异率3.3%(P<0.05); 治疗组在用药52周的HBV YMDD变异率为24.0%,明显高于用药26周时的变异率4.0%(P<0.05);治疗前HBV DNA水平较高组用药52周时的变异率为35.7%,明显高于HBV DNA水平较低组的变异率9.1%(P<0.05);治疗组中未变异组在用药52周时的HBV DNA阴转率为65.8%,明显高于变异组的HBV DNA阴转率16.7%(P<0.05).结论拉米夫定可导致HBV YMDD变异的产生,并且该变异的发生率随着拉米夫定用药时间延长而增加;治疗前血清HBV DNA水平较高者在应用拉米夫定后易发生YMDD变异;HBV YMDD变异发生后,可出现HBV DNA复升,但一般不会超过治疗前的基线水平.     

乙肝病毒前C基因变异对宿主T细胞亚群的影响及其临床意义的研究

目的　通过检测乙型肝炎病毒 (HepatitisBVirus,HBV)变异株感染患者外周血T细胞亚群分布的变化 ,探讨HBV基因组前C区 1896位基因变异与宿主机体免疫水平的关系 .方法　用酶联免疫吸附试验 (ELISA)检测 5 5名患者血清乙型肝炎病毒标志物 (HBVM)HBsAg ,抗 HBs,HBeAg ,抗HBe及抗 HBc;采用定性PCR法检测上述患者血清HBVDNA ;通过限制性片段长度多态性分析法 (RFLP)检测发生前C区 1896位基因突变的HBV变异株 ;采用流式细胞术 (flowcytometry)对上述患者外周血的CD4 + T细胞 ,CD8+ T细胞 ,CD3+ T细胞含量进行检测 ,将检测结果同所设健康对照组进行比较 ,并对数据进行统计学分析 .结果　在 5 5名患者中 ,HBsAg(+) ,anti HBs(- ) ,HBeAg(+) ,anti HBe(- ) ,anti HBc(+)者共 2 2例 ,其HBVDNA检测结果均为阳性 ,在这2 2例患者中 ,有 2 0例被检出为单纯HBV野毒株感染 ,另有 2例被检出为变异株和野毒株混合感染 ;HBsAg(+) ,anti HBs(- ) ,HBeAg(- ) ,anti HBe(+) ,anti HBc(+)者共 33例 ,其中HBVDNA阳性者为 18例 .在 18例HBeAg(- )而HBVDNA (+)的患者中 ,有 17例被检出为HBV前C区 1896位变异株感染 .变异株感染患者外周血CD4 + T细胞含量较之健康对照组有所减低 (P <0 .0 1) ,CD8+ T细胞含量较之健康对照组也有所     

PCR扩增检测献血者中TT病毒DNA及部分TTV基因序列分析

目的：了解江苏地区献血者中新型肝炎相关病毒－－TT病毒的感染状况,探讨TTV感染与ALT异常的相关性,方法：设计通用引物,采用半套式聚合酶链反应（hemi-nested PCR)方法检测195份献血者血清标本,结果,在血清丙氨酸转氨酶（ALT）异常,HBsAg及抗HCV阴性的99份献血者血清标本中,检出TTV DNA阳性标本36份,TTV DNA的阳性检出率为36．3％,而在96份正常献血者血清标本中,检出TTV DNA阳性标本16份,TTV DNA阳性检出率为16．6％,明显低于ALT常献血者人群,对2株阳性株序列分析结果显示,一株与TX011（G1b日本代表株）的同源性为98．6％,属于G1b亚型,另一株虽可归属于G1,但与G1a ,Blb差异较大,可能为G1的新亚型,结论：江苏地区献血者人群中存在TTV感染,国内首次报告检出TTV G1b亚型及新的亚型,献血者ALT异常与TTV感染密切相关,输血可能成为传播TTV感染的途径之一。     

A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice

Public health measures have successfully identified and contained outbreaks of the severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), but concerns remain over the possibility of future recurrences. Finding a vaccine for this virus therefore remains a high priority. Here, we show that a DNA vaccine encoding the spike (S) glycoprotein of the SARS-CoV induces T cell and neutralizing antibody responses, as well as protective immunity, in a mouse model. Alternative forms of S were analysed by DNA immunization. These expression vectors induced robust immune responses mediated by CD4 and CD8 cells, as well as significant antibody titres, measured by enzyme-linked immunosorbent assay. Moreover, antibody responses in mice vaccinated with an expression vector encoding a form of S that includes its transmembrane domain elicited neutralizing antibodies. Viral replication was reduced by more than six orders of magnitude in the lungs of mice vaccinated with these S plasmid DNA expression vectors, and protection was mediated by a humoral but not a T-cell-dependent immune mechanism. Gene-based vaccination for the SARS-CoV elicits effective immune responses that generate protective immunity in an animal model.     

树对人乙型肝炎病毒易感性的验证

为验证树对人乙型肝炎病毒 (HBV)的易感性 ,用含 HBV的人血清接种给 10只成年树 (雌雄各半 )。然后每周抽血 1次 ,每只动物共抽血 11次。用不同公司生产的 EL ISA试剂检测接种后的动物血清感染指标。实验观察至 13周 ,结果分别有 9只和 7只动物出现 HBs Ag阳性 ,持续最短 1周 ,最长 7周。用 PCR检测 ,结果有 1只动物连续 4周在血清中检测出 HBV DNA。表明树能感染人 HBV,但实验有待改进以延长感染持续时间     

HTLV-III-neutralizing antibodies in patients with AIDS and AIDS-related complex

The isolation of the human T-cell leukaemia (lymphotropic) virus type III (HTLV-III or lymphadenopathy-associated virus) from cells of many patients with acquired immune deficiency syndrome (AIDS) presented the first evidence that the virus was the aetiological agent of the disease. Subsequent seroepidemiological studies have shown the presence of HTLV-III-specific antibodies in the serum of most patients with AIDS and AIDS-related complex (ARC), and in the serum of many individuals at risk for AIDS. Despite these extensive studies, there are no reports of protective effects of HTLV-III antibodies. In contrast, neutralizing antibodies specific for HTLV-I and -II have been identified previously. Therefore, we investigated whether HTLV-III-exposed individuals possess antibody activities capable of inhibiting viral infection. Here, we report that natural antibodies capable of neutralizing HTLV-III infection of H9 cells were detected in most adults AIDS and ARC patients but in no normal healthy heterosexual controls. Geometric mean antibody titres in ARC patients were double those in AIDS patients, and were even higher in two antibody-positive healthy homosexuals. This suggests that virus neutralizing antibodies may exert an in vivo protective effect. The presence of these antibodies indicates an immunological response to HTLV-III which potentially may be manipulated for therapeutic advantage. The methodology used here will be useful in monitoring future vaccine approaches.