Comparison of carrier proteins to conjugate malaria transmission blocking vaccine antigens,Pfs25 and Pfs230

Malaria transmission blocking vaccines (TBV) target the sexual stage of the parasite and have been pursued as a stand-alone vaccine or for combination with pre-erythrocytic or blood stage vaccines. Our efforts to develop TBV focus primarily on two antigens, Pfs25 and Pfs230. Chemical conjugation of these poorly immunogenic antigens to carrier proteins enhances their immunogenicity, and conjugates of these antigens to Exoprotein A (EPA) are currently under evaluation in clinical trials. Nonetheless, more potent carriers may augment the immunogenicity of these antigens for a more efficacious vaccine; here, we evaluate a series of proteins to identify such a carrier. Pfs25 and Pfs230 were chemically conjugated to 4 different carriers [tetanus toxoid (TT), a recombinant fragment of tetanus toxin heavy chain (rTThc), recombinant CRM₁₉₇ produced in Pseudomonas fluorescens (CRM197) or in E. coli (EcoCRM®)] and compared to EPA conjugates in mouse immunogenicity studies. Conjugates of each antigen formulated in Alhydrogel® elicited similar antibody titers but showed differences in functional activity. At a 0.5 µg dose, Pfs230 conjugated to TT, CRM197 and EcoCRM® showed significantly higher functional activity compared to EPA. When formulated with the more potent adjuvant GLA-LSQ, all 4 alternate conjugates induced higher antibody titers as well as increased functional activity compared to the EPA conjugate. IgG subclass analysis of Pfs230 conjugates showed no carrier-dependent differences in the IgG profile. While Alhydrogel® formulations induced a Th2 dominant immune response, GLA-LSQ formulations induced a mixed Th1/Th2 response.     

兰州地区464例遗传咨询病人的染色体分析

目的探讨染色体异常在遗传咨询病人中的发生情况.方法取受检者外周血进行淋巴细胞培养,常规收获制片,G显带处理,显微镜下进行核型分析.结果在464例病人中共检出染色体异常24例,染色体异常检出率为5.17%,其中平衡易位3例(12.5%),罗伯逊易位3例(12.5%),倒位5例(20.83%),性染色体异常8例(33.33%),染色体不平衡易位5例(20.83%).结论妇产科及生殖内分泌许多疾病与染色体异常有关,对这些病人进行染色体检查很有必要.     

2005—2020年玉溪市乙型病毒性肝炎流行趋势及防控对策

目的 分析2005—2020年玉溪市乙型病毒性肝炎流行特征和趋势,为今后乙型病毒性肝炎防制工作提供科学依据。方法 采用描述性流行病学方法,对玉溪市2005—2020年疾病监测信息报告管理系统报告的乙型病毒性肝炎和乙肝携带者疫情资料进行分析。结果 2005—2020年共报告乙肝病例11 721例,年均发病率为32.44/10万,16年间呈现下降趋势(χ²_趋势=1 244.406,P=0.001)。乙肝携带者累计报告17 179例,年均报告率为46.59/10万,总体却呈现上升趋势(χ²_趋势=824.577,P=0.002)。各县区乙肝病例年均报告发病率差异有统计学意义(χ²=26.214,P=0.011),居前3位的县区依次为华宁县54.57/10万、易门县41.37/10万和通海县40.36/10万。各县区乙肝携带者年均报告率差异有统计学意义(χ²=81.360,P=0.015),居前3位的县区依次为华宁县201.60/10万、峨山县75.03/10万和新...     

Clinical Characteristics of Patients in Their 40s With HCV Antibody-Positive Hepatocellular Carcinoma

Background: We investigated the clinical characteristics of hepatitis C virus (HCV) antibody-positive hepatocellular carcinoma (HCC) patients who developed HCC at a relatively young age. Methods: Clinical characteristics of patients in their 40s were investigated and were compared with those of patients 50 years and older. The subjects were 648 HCC patients, 469 men (72%) and 179 women (28%), who were treated at our hospital between 1991 and 1997. Results: No patient was under 40 years of age. Eighteen patients (3%) were in their 40s, 137 patients (21%) were in their 50s, 338 patients (52%) were in their 60s, 143 patients (22%) were in their 70s, and 12 patients (2%) were in their 80s. Fifteen of the patients (83%) in their 40s were male. The proportion of men in their 40s was higher than that of all men. Eight of the 15 men in their 40s (53%) were heavy drinkers, and 2 (14%) were habitual drinkers. Three of the 15 men (20%) were HBV carriers, and these 3 HBV carriers were not drinkers. The proportion of heavy drinkers and HBV carriers was significantly higher among the patients in their 40s than in the 60 patients randomly sampled from the patients 50 years of age and older. The mean ages of male patients with HCC who were heavy drinkers, habitual drinkers, occasional drinkers, or nondrinkers were 52.3, 58.9, 62.0, and 61.7 years, respectively. HCC occurred significantly earlier in heavy drinkers than in the other 3 groups. We compared laboratory data of the patients in their 40s with data of all of the patients of 50 years and older. Serum total bilirubin, prothrombin time, and platelet counts were significantly worse in the patients in their 40s. Conclusions: Logistic regression analysis revealed that heavy drinking and presence of HBV infection were independently related to HCV antibody-positive HCC development at a younger age.     

肿瘤浸润性淋巴细胞结合偶联半乳糖抗CD3单克隆抗体的肝脏靶向性研究

目的　探讨结合偶联半乳糖（ Ｇａｌａｃｔｏｓｅ , Ｇａｌ） 抗 Ｃ Ｄ３ 单克隆抗体（ Ａｎｔｉ Ｃ Ｄ３ Ｍｃ Ａｂ） 肿瘤浸润性淋巴细胞（ Ｔｕｍｏｒｉｎｆｉｌｔｒａｔｉｎｇ ｌｙｍｐｈｏｃｙｔｅｓ , Ｔ Ｉ Ｌ） 肝脏靶向性。 方法　本组把大鼠抗小鼠 Ｃ Ｄ 单克隆抗体和半乳糖偶联在一起,与３ Ｈ Ｔｄ Ｒ 标记 Ｔ Ｉ Ｌ结合后,从鼠尾静脉注入小鼠体内,在注射不同时间眼眶取血０５ ｍｌ,然后处死,切除肝、脾、肺,分别称重后进行放射性强度测定。 结果　结果显示：注射 Ｇａｌａｎｔｉ Ｃ Ｄ３ Ｍｃ Ａｂ Ｔ Ｉ Ｌ小鼠肝脏比注射单纯 Ｔ Ｉ Ｌ 的小鼠肝脏具有较高的放射性（ Ｐ＜ ００１） ,且该放射性持续较长一段时间,而脾、肺、血液内放射性强度差异无显著意义（ Ｐ＞ ００５ , Ｐ＞ ００５ , Ｐ＞ ００５） 。结论　该结果提示： Ｇａｌａｎｔｉ Ｃ Ｄ３ Ｍｃ Ａｂ Ｔ Ｉ Ｌ较单纯 Ｔ Ｉ Ｌ具有更好的肝脏靶向性。     

聚乳酸和无活性脱钙骨基质载体对rhBMP-2异位诱导骨形成的比较性研究

目的：为了研究聚乳酸和无活性脱钙骨基质载体对ｒｈＢＭＰ－２异位诱导的骨形成。方法：将重组人骨形态发生蛋白－２（ｒｈＢＭＰ－２）与无活性脱钙骨基质（ＤＢＭ）和聚乳酸（ＰＬＡ）复合,植入小鼠股部外侧肌肉陷窝比较ＰＬＡ和ＤＢＭ载体对ｒｈＢＭＰ－２诱导骨形成的影响。通过组织学检查、碱性磷酸酶（ＡＬＰ）和钙含量测定以及骨钙素（ＢＧＰ）放疫测定,进行对比观察。结果：术后２１天,实验组均可见新生软骨细胞和软骨岛,ｒｈＢＭＰ－２／ＰＬＡ和ＤＢＭ／ｒｈＢＭＰ－２组还可见部分骨组织形成,见骨小梁、板层结构和红骨髓,ｒｈＢＭＰ－２／ＰＬＡ组ＰＬＡ部分吸收,ＤＢＭ／ｒｈＢＭＰ－２组ＤＢＭ无吸收迹象。各实验组与对照组对比,ＡＬＰ、ＢＧＰ水平和Ｃａ量均有显著性差异（Ｐ＜０．０５）,ｒｈＢＭＰ－２／ＰＬＡ与ＤＢＭ／ｒｈＢＭＰ－２组在ＡＬＰ和ＢＧＰ水平上相比无显著差异（Ｐ＞０．０５）,但前组比后组的Ｃａ量为高（Ｐ＜０．０５）,这二组与单独植入ｒｈＢＭＰ－２组相比,定量检测指标均有显著性差异（Ｐ＜０．０５）。结论：（１）ＰＬＡ和ＤＢＭ均为ＢＭＰ的良好载体;（２）ｒｈＢＭＰ－２／ＰＬＡ是一种新的有价值的骨修复材料     

肺炎链球菌耐药性和血清型分布及隐匿性耐药克隆株的研究

目的 了解儿童肺炎链球菌携带者耐药菌株的流行情况,比较携带者菌株血清型与肺炎链球菌结合疫苗血清型的符合率,寻找单个患儿同时携带第三和耐药菌株的可能性。方法 （１）对１９９７年１１月～１２月在北京儿童医院普通门诊登记的３个月～５岁儿童进行问卷调查;（２）采集鼻咽拭子和尿标本,培养、分离和鉴定肺炎链球菌,并测定尿标本中的抗生素活性;（３）根据ＮＣＣＬＳ方法使用微量稀释法测定肺炎链球菌对青霉素、头孢呋新     

融合蛋白TOP_3原核表达载体的构建、表达及纯化研究

目的:利用HIV病毒TAT蛋白转导结构域、人缺氧诱导因子1α氧依赖降解结构域以及CASPASE3构建融合蛋白的原核表达载体,并在大肠杆菌中表达及纯化。方法:分别构建原核表达质粒pET-28a(+)-TAT、pET-28a(+)-TAT-ODD、pET-28a(+)-TAT-ODD-CASPASE3(pET-28a(+)-TOP3);在大肠杆菌BL21(DE3)pLysS内,利用镍-亚硝胺乙酸-组氨酸(Ni-NTA-His)亲和层析法对重组蛋白TOP3进行纯化。结果:成功构建了pET-28a(+)-TOP3的原核表达载体,经过优化表达和纯化条件,融合蛋白在IPTG诱导下获得特异性表达,纯化得到了高纯度的目的蛋白。结论:融合蛋白TOP3的成功表达及纯化,为该融合蛋白应用于肿瘤的治疗研究奠定了理论基础。