Immunogenicity and safety of a novel yeast Hansenula polymorpha-derived recombinant Hepatitis B candidate vaccine in healthy adolescents and adults aged 10–45 years

The aim was to determine whether the immunogenicity of an investigational hepatitis B vaccine (spHB) is at least as high as that of a licensed control vaccine, Engerix B^®, and to evaluate its safety before inclusion in new pediatric combination vaccines. Two randomized, controlled, blind-observer, Phase 3 trials were performed: one in Argentina (344 participants aged 10–15 years, 10 μg HBsAg/dose) and one in Uruguay (344 participants aged 16–45 years, 20 μg HBsAg/dose). Both vaccines were given in a 0, 1, 6 month schedule to all participants with a baseline anti-Hep B antibody titer <0.6 mIU/mL. Antibody titers were measured pre-dose 1, 1 month after dose 2, pre-dose 3, and 1 month after dose 3. Statistical non-inferiority analyses were performed on seroprotection rates (SP) post-dose 3 (% with anti-Hep B titers ≥10 mIU/mL; delta non-inferiority limit of −10%). In both studies, SP for the spHB vaccine was 100% and the spHB vaccine was non-inferior in terms of SP to the licensed control vaccine. GMTs post-dose 3 were approximately 1.8- and 4.1-fold higher for spHB in the 10–15 year and 16–45 year age groups, respectively. Reactogenicity was low for each vaccine, after each dose. This highly immunogenic hepatitis B candidate vaccine was selected for further investigation as a component of new pediatric combination vaccines.     

慢性乙型肝炎患者病毒e系统状态与肝纤维化关系的研究

目的:观察慢性乙型肝炎患者乙型肝炎病毒e系统状态和复制指标在肝纤维化发生过程中的变化及其与血清纤维化标志的关系,探讨它们在肝纤维化发生过程中的作用及其可能的临床意义.方法:188例慢性乙型肝炎患者根据肝纤维化程度分为S0～S4期等5组,分别用定量PCR及放免法检测患者血清中HBV-DNA及肝纤维化标志透明质酸、Ⅳ型胶原、Ⅲ型前胶原和层粘连蛋白的含量;HBeAg和抗-HBe采用酶联免疫吸附法(ELISA)检测,并观察其在不同肝病理纤维化分期时的变化.结果:随着肝纤维化程度加重,血清HBV-DNA含量逐渐升高,从S1期开始显著增加(P＜0.01);而HBeAg阳性率逐渐降低,S3、S4期较S0显著减少(P＜0.05和P＜0.01);抗-HBe阳性率呈相反的变化趋势,在S3和S4期的阳性率明显高于S0期(P＜0.05和P＜0.01).血清HBV-DNA( )HBeAg( )组血清纤维化标志最低,HBV-DNA(-)抗-HBe( )组最高,两者差异有显著性(P＜0.01).结论:HBV复制和e系统状态的改变与肝纤维化程度密切相关,肝内病毒复制标志与血清纤维化标志联合检测,对于判断肝纤维化程度和指导抗病毒治疗有重要的价值.     

95例SARS患者T细胞及其亚群动态变化的观察

对 95例SARS患者的T淋巴细胞亚群动态变化进行分析。其中 85例痊愈 ,1 0例死亡。 85例痊愈患者 ,病程第 7天平均CD4 + ( 3 2 5± 1 90 )个 /μL ,CD8+ ( 3 1 9± 3 1 5 )个 /μL ,CD4 + /CD8+ 1 .2 5± 0 .71 ,与我国正常人相比〔平均CD4 + ( 72 7± 2 5 5 )个 /μL、CD8+ ( 5 3 9± 1 3 4)个 /μL ,CD4 + /CD8+ 1 .49〕 ,T淋巴细胞亚群明显下降 (P =0 .0 0 1 )。病程第1 4天左右免疫功能逐渐恢复 ,平均CD4 + ( 5 61± 5 2 2 )个 /μL ,CD8+ ( 3 70± 2 71 )个 /μL ,CD4 + /CD8+ 1 .68± 1 .1 1。 2 1d后免疫功能基本恢复正常 ,平均CD4 + ( 675± 448)个 /μL ,CD8+ ( 4 67± 2 41 )个 /μL ,CD4 + /CD8+ 1 .48± 0 .68。 1 0例死亡患者的T细胞亚群在入院后逐渐出现下降趋势 ,病程第 7天CD4 + ( 2 48± 82 )个 /μL ,CD8+ ( 2 3 3± 1 1 5 )个 /μL ,CD4 + /CD8+ 1 .2 1± 0 .40 ,第 1 4天T淋巴细胞继续下降 ,平均CD4 + ( 1 81± 1 2 8)个 /μL ,CD8+ ( 1 73± 1 0 9)个 /μL ,CD4 + /CD8+ 1 .1 7± 0 .45 ,2 1d后CD4 + 细胞继续下降 ,平均CD4 + ( 1 2 5± 46)个 /μL ,CD8+ ( 94± 3 8)个 /μL ,CD4 + /CD8+ 1 .44±0 .5 9。结果提示 :SARS患者早期可能存在异常的免疫反应 ,这种异常免疫反应可能是导?     

多器官功能障碍小鼠高迁移率族蛋白1释放对单个核细胞免疫相关指标的影响

目的 分析多器官功能障碍综合征(MODS)小鼠血清高迁移率族蛋白B1(HMGB1)含量的变化与外周血中单个核细胞免疫相关指标变化的关系,观察MODS发生、发展中HMGB1释放的规律及其对细胞免疫功能的影响.方法 腹腔注射酵母多糖复制小鼠MODS模型,用Westernblot法检测病程不同阶段血清HMGB1含量、流式细胞术测定外周血单核细胞表面组织相容性复合体-Ⅱ类分子(MHC-Ⅱ类分子,IAb)的表达量及T淋巴细胞亚群的比值(CD4+/CD8+).结果 在酵母多糖所致小鼠MODS模型中,当血清HMGB1含量升高时,外周血单核细胞IAb表达量及CD4+/CD8+比值下降;当血清HMGB1含量回复接近正常时,单核细胞IAb表达量及CIM4+/CD8+比值也趋于恢复正常.结论 在MODS的发生、发展过程中,HMGB1可能通过影响血中单个核细胞MHC-Ⅱ类分子(IAb)表达及T淋巴细胞的活性参与免疫调节过程,导致免疫失衡或免疫抑制.     

Flavocoxid is as effective as naproxen for managing the signs and symptoms of osteoarthritis of the knee in humans: a short-term randomized,double-blind pilot study

Flavocoxid (Limbrel), a proprietary mixture of flavonoid molecules (baicalin and catechin), was tested against a traditional nonsteroidal anti-inflammatory drug, naproxen, for the management of the signs and symptoms of moderate osteoarthritis (OA) in humans. Discomfort and global disease activity were used as the primary end points, and safety assessments were also taken for both treatments as a secondary endpoint. In this double-blind study, 103 subjects were randomly assigned to receive either flavocoxid [500 mg twice daily (BID)] or naproxen (500 mg BID) in a 1-month onset of action trial. Outcome measures included the short Western Ontario and McMaster University Osteoarthritis Index, subject Visual Analogue Scale for discomfort and global response, and investigator Visual Analogue Scale for global response and fecal occult blood. Both flavocoxid and naproxen showed significant reduction in the signs and symptoms of knee OA (P ≤ .001). There were no statistically detectable differences between the flavocoxid and naproxen groups with respect to any of the outcome variables. Similarly, there were no statistically detectable differences between the groups with respect to any adverse event, although there was a trend toward a higher incidence of edema and nonspecific musculoskeletal discomfort in the naproxen group. In this short-term pilot study, flavocoxid was as effective as naproxen in controlling the signs and symptoms of OA of the knee and would present a safe and effective option for those individuals on traditional nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors. A low incidence of adverse events was reported for both groups.     

HBV转录激活蛋白HBx、MHBst78MHBst155真核重组载体构建

目的分别构建人乙型肝炎病毒(HBV)X蛋白、羧基端截断的中分子表面蛋白MHBst78、MHBst155编码基因的真核重组表达载体,以便进一步研究其转录激活功能及对宿主细胞信号传导通路的影响。方法设计合成3对寡核苷酸引物,以adr亚型HBV质粒pHBVDNA为模板,采用PCR法分别扩增HBVX基因、MHBst78与MHBst155编码基因片段;用HindⅢ,KpnⅠ双酶切HBVⅩ基因;用HindⅢ和BamHⅠ双酶切MHBst78与MHBst155编码基因片段后,分别定向插入到真核表达载体pcDNA3.1相应酶切位点,转化宿主菌JM109,提取质粒,分别用上述内切酶酶切及DNA测序鉴定重组质粒。结果酶切重组体显示所切下的片段大小均与预计相符,测序结果与文献报道序列及预计结果一致。结论成功构建了HBVX基因、羧基端截断的HBV中分子表面蛋白MHBst78、MHBst155编码基因的真核重组表达载体,为进一步研究HBV转录激活蛋白HBx、MHBst78MHBst155对宿主细胞信号转导通路的影响奠定基础。     

合并乙肝的涂阳肺结核病人DOTS中肝损害观察

目的 观察免费板式组合药在DOTS中对合并乙肝的涂阳肺结核病人肝损害情况。方法 比较HBsAg、HBeAg、HBcAb阳性的涂阳肺结核病人与无乙肝的涂阳肺结核病人DOTS前后肝功能损害情况。结果 合并乙肝病人肝损害发生率66．3％，无乙肝者肝损害发生率8．6％，两者相比差异有显著性（P〈0．01）。22．5％病人因肝损害需更改治疗方案。结论 DOTS中合并乙肝的病人采用板式组合药用2H3R3Z3E3／4H3R3方案易发生肝损害，对这类病人应慎用常规方案，并要密切全程观察肝功能，尽可能应用肝损害较小的抗结核药。     

Triterpenoid saponins, new metalloprotease snake venom inhibitors isolated from Pentaclethra macroloba.

We report here the antiproteolytic and antihemorrhagic properties of triterpenoid saponin inhibitors, named macrolobin-A and B, from Pentaclethra macroloba, against Bothrops snake venoms. The inhibitors were able to neutralize the hemorrhagic, fibrin(ogen)olytic, and proteolytic activities of class P-I and P-III metalloproteases isolated from B. neuwiedi and B. jararacussu venoms. Clotting and fibrinogenolytic activities induced by snake venoms and isolated thrombin-like enzymes were partially inhibited. Furthermore, the potential use of these inhibitors to complement antivenom therapy as an alternative treatment and/or used as molecular models for development of new therapeutical agents in the treatment of snake bite envenomations needs to be evaluated in future studies.     

脂质体介导NF-κB decoy ODN对重症急性胰腺炎大鼠肺炎症因子mRNA表达和肺损伤的影响

目的 探讨脂质体（liposome）介导转录因子NF—κB诱捕物（decoy）寡聚脱氧核苷酸（oligodeoxynucleotide，ODN）对重症急性胰腺炎SD大鼠肺部NF-κB活性及受其调控炎症基因mRNA表达和肺损伤的影响。方法 以牛磺胆酸钠（STC）诱导SD大鼠建立重症急性胰腺炎模型，以假手术组为对照组，于建模后1h分别静脉注射裸ODN、脂质体／decoy ODN复合物、脂质体／scrambled ODN复合物和生理盐水，注射4h后应用电泳迁移率变动（EMSA）分析NF-κB的活性，利用逆转录-聚合酶链反应法（RT-PCR）检测肺组织ICAM-1、IL-1α、IL-2、TNF—α、VCAM-1mRNA表达，同时检测氧分压、肺组织湿／干重比率和肺组织髓过氧化物酶（MPO）。结果 EMSA显示脂质体／decoy ODN复合物组NF—κB活性明显低于生理盐水组、脂质体／scrambled ODN复合物组和裸ODN组（P〈0.05），RT—PCR显示脂质体／decoy ODN复合物组ICAM-1、IL-1α、IL-2、TNF—α、VCAM-1mRNA表达小于生理盐水组、脂质体/scrambled ODN复合物组和裸ODN组（P〈0．05）。与生理盐水组、脂质体／scrambled ODN复合物组和裸ODN组相比，脂质体／decoy ODN复合物组动脉血氧分压升高，肺组织湿／干重比率和肺组织髓过氧化物酶（MPO）活性降低（P〈0．05）、结论 NF—κB decoy ODN可特异性抑制肺NF-κB活性及其调控的炎症因子ICAM-1、IL—1α、IL-2、TNF-α、VCAM-1mRNA的表达，减轻肺损害。     

Massive Immune Hemolysis Caused by Anti-D After Dual Kidney Transplantation

Massive immune hemolysis due to passenger lymphocyte-derived anti-D has not been reported in renal transplantation. A 50-year-old (B-positive) male received a dual deceased-donor kidney transplant (B-negative) for diabetic renal failure. Two weeks post-transplant, the patient developed severe hemolytic anemia. The donor anti-D titer was 1:8. The recipient anti-D titer (zero pre-transplant) increased from 1:4 to 1:16 over 4 days. Rapid hemolysis caused severe anemia, minimum Hb = 4.2 g/dL, while selectively lysing the patient's autologous red cells during this time. The hemolytic anemia did not impair the allografts and subsided without monoclonal B-cell pharmacotherapy or apheresis. The anti-D titer decreased to barely detectable levels at four months and had cleared when checked 2 years post-transplant. Transfusion support subsided after two months. If complications of anemia can be avoided, the deleterious effects of hemolysis may be well tolerated by renal allografts using antigen negative transfusion alone.