如何改进治疗性抗体的安全性和疗效特征

自从首次发现单克隆抗体（MAbs）在医药和工业中可能存在的应用价值后,它们已被经常·性地用于研究和诊断试验室中,而对其用于治疗的可能·性的研究正在以指数级的速度推进。现在,MAbs成为了发展最快的一类蛋白治疗性抗体,当前主要被研发用于治疗癌症、自身免疫性疾病、感染性疾病和炎。性疾病。它们代表了生物技术行业内出现的销量最大的一类制品一治疗’性抗体。截止2008年年底,美国治疗性抗体的市场估计价值达40bn美元,预计抗体很快就会超越较大制药市场的销售额。     

基于免疫克隆算法的多枢纽选址与混合网络设计综合优化研究

为了描述多枢纽选址与混合网络设计综合优化问题,引入了双层规划模型建立数学模型.上层模型为多目标规划模型,以最小化网络总阻抗和最小化总投资为目标;下层模型为固定需求的用户平衡配流模型.然后,给出了基于免疫克隆算法的具体求解设计和步骤.接着,给出了算例,在不同决策权重条件下进行求解.算例结果验证了算法的可行性和模型的有效性,同时结果表明在建设枢纽后,当决策偏重于交通网络管理部门时,更倾向于建设新路段以降低网络费用和总费用.     

Biological properties of differently-aged human keratinocytes.population doubling time growth curve and cell cycle analysis

Objective To explore the biological properties of keratinocytes from differently-aged healthy human beings. Methods Keratinocytes from fetus, teenager and middle-aged groups were separated and cultured. The population doubling time (PDT) and cell growth curve in different cells were compared, and the cell cycles were analyzed by flow cytometry. Results ① In primary culture of keratinocytes, the adherence time in middle-aged group was longer than that in fetus and teenager groups. However, all cell morphology showed no obvioas differences. In subculture of kecatinocytes, with donator's age increasing, time of cell adherence prolonged, passage number decreused and differences in cell morphology were obrioas. ② The average PDT of keratinocytes was shorter in fetus group than in teenager and middle-aged groups. Bat difference in cell growth curve between different passages was not observed. ③ Keratinocytes showed G2/M period in fetus group but G0/G1 period in teenager and middle-aged groups mainly. Conclusion As age increases, the biological properties of keratinocytes change obviously.     

顺铂对小鼠耳蜗毒性及caspase-3表达的影响

目的 建立小鼠顺铂耳毒性模型,研究不同剂量顺铂对小鼠耳蜗毒性及caspase-3表达的影响.方法 69只昆明小鼠随机分成对照组、顺铂2.5mg/(kg·d)组、顺铂3.5mg/(kg·d)组和顺铂4.5mg/(kg·d)组,腹腔连续注射5d.通过听脑干反应(auditory brainstem response, ABR)测试观察用药前后小鼠听力的变化;应用免疫组织化学Envision法检测半胱天冬氨酸蛋白酶-3(caspase-3)在耳蜗中的表达.结果 不同剂量顺铂组小鼠体重和听力明显下降,与对照组比较均有显著性差异(P<0.05,P<0.01);并且随着顺铂给药剂量的增加,小鼠耳蜗中caspase-3表达亦明显增强.结论 应用顺铂可建立小鼠耳毒性模型;caspase-3参与了顺铂致小鼠耳蜗细胞损伤的过程,提示内耳细胞凋亡可能是顺铂的耳毒性机制之一.     

Intelligent optimization of the structure of the large section highway tunnel based on improved immune genetic algorithm

As in the building of deep buried long tunnels, there are complicated conditions such as great deformation, high stress, multi-variables, high non-linearity and so on, the algorithm for structure optimization and its application in tunnel engineering are still in the starting stage. Along with the rapid development of highways across the country, It has become a very urgent task to be tackled to carry out the optimization design of the structure of the section of the tunnel to lessen excavation workload and to reinforce the support. Artificial intelligence demonstrates an extremely strong capability of identifying, expressing and disposing such kind of multiple variables and complicated non- linear relations. In this paper, a comprehensive consideration of the strategy of the selection and updating of the concentration and adaptability of the immune algorithm is made to replace the selection mode in the original genetic algorithm which depends simply on the adaptability value. Such an algorithm has the advantages of both the immune algorithm and the genetic algorithm, thus serving the purpose of not only enhancing the individual adaptability but maintaining the individual diversity as well. By use of the identifying function of the antigen memory, the global search capability of the immune genetic algorithm is raised, thereby avoiding the occurrence of the premature phenomenon. By optimizing the structure of the section of the Huayuan tunnel, the current excavation area and support design are adjusted. A conclusion with applicable value is arrived at. At a higher computational speed and a higher efficiency, the current method is verified to have advantages in the optimization computation of the tunnel project. This also suggests that the application of the immune genetic algorithm has a practical significance to the stability assessment and informationlzation design of the wall rock of the tunnel.     

Ti基生物材料表面促内皮／抗凝双功能修饰层的构建与化学生物学评价

心脑血管疾病是生命医学科学领域的难题,也是人类死亡的首要原因。目前,世界上每年约2000万人死于心血管疾病,而我国死于心脑血管疾病的人数已占国人死亡总数的一半。在临床心脑血管疾病的治疗中,血管支架（支撑病人堵塞或不畅的血管）、人工心脏瓣膜（置换病人丧失功能的心瓣）、血栓滤器等心血管移植物被普遍使用。     

幽门螺杆菌、高胃泌素血症对结直肠癌形成的影响

目的探讨H.pylori感染、高胃泌素血症与结直肠癌形成三者之间的相互关系及H.pylori在结直肠癌组织中的表达情况。方法采用放射免疫法(RIA)测定结直肠癌患者(51例)及对照组(43例)的血清胃泌素水平,用ELISA法检测H.pylori IgG抗体,用免疫组化的方法观察H.pylori在结直肠癌组织中的表达情况。结果肿瘤组患者H.pylori感染阳性率、血清胃泌素水平明显高于对照组(P<0.05),远端结肠与直肠患者H.pylori阳性率显著高于近端结肠患者(P<0.05),同时高胃泌素血症患者的比例明显高于近端结肠患者(77.8%vs.37.5%,80.0%vs.37.5%,P<0.05);并且随着肿瘤分期升高,二者比例均同步升高。此外,在结直肠癌组中,8例(15.7%)患者观察到H.pylori阳性表达,表现为模糊的颗粒状或粗杆状黏膜染色图形;而在对照组的结直肠组织中H.pylori未见表达。结论用免疫组化的方法可以证明H.pylori存在于结直肠癌组织中,尤其是血清H.pylori阳性并高胃泌素血症的患者;H.pylori感染可能诱导高胃泌素血症并与结直肠癌的形成有关。     

HtrA1在宫颈上皮内瘤样病变及宫颈鳞癌中的表达及临床意义

目的探讨HtrA1在宫颈鳞状上皮内瘤样病变(CIN)及宫颈鳞癌中的表达及临床意义。方法采用免疫组化S-P法对10例正常宫颈、28例CIN(其中轻度8例、中度10例、重度10例)、25例原位癌及40例宫颈浸润鳞癌标本中HtrA1的表达进行检测,并与临床病理分级等进行相关分析。结果正常宫颈组织中HtrA1无阳性表达。CIN、原位癌的阳性表达率分别为21.4%及60%,各组间差异有统计学意义(P<0.05)。浸润癌阳性表达率为52.5%,较原位癌组显著降低(P<0.05)。HtrA1阳性表达率与宫颈癌临床分期呈负相关(r=-0.622,P<0.05),与病理分级无关(P>0.05)。无淋巴结转移者HtrA1阳性表达明显高于有淋巴结转移者(P<0.05)。结论 HtrA1表达对宫颈癌的发生发展及评估预后有重要意义,可能是一种肿瘤抑制因子。     

多式联运运输方式选择的模型和算法

在对多式联运运输方式选择问题分析的基础上,运用图论技术构建基于多种运输方式的运输网络.综合考虑了运输成本、运输时效性和运输风险,建立了基于综合运输成本最小和运输风险最小的多目标综合优化模型.通过主要目标法,将模型进行转化.设计了基于克隆增扩的人工免疫算法对问题进行求解.最后通过算例验证了模型和算法的有效性.     

染镉小鼠体内淋巴细胞转化的抑制

Cd是主要的工业污染金属之一,较广泛地存在于工业环境和受污染的生活环境中。其对人及动物的某个器官或某个系统的毒性,国内外已进行了大量的研究。近年来又开展了Cd对免疫系统影响的研究。国内外的一些研究表明,Cd可抑制体内外的抗体生成反应和体外淋巴细胞增殖反应。但未见整体动物接触Cd对体内淋巴细胞转化影响的报道。