对住院内科患者开展人性化护理服务的调查

目的详细了解内科患者在住院期间对人性化护理服务的需求，探讨人性化护理的服务措施。方法采用自行设计的调查问卷对60名内科住院患者进行调查，调查内容包括环境和护理服务两方面。结果内科患者在环境和健康教育方面的需求强烈，同时在护理服务的细节、护士的仪表和语言上也提出了合理的建议。结论为进一步提高护理服务质量，应从营造一个良好的住院环境和提供优质、全面的护理服务人手，注重患者的心理需求和人格尊严，真正体现人性化的服务理念。     

盖洛普Q12对护士工作满意度的影响及应用研究

目的探讨什么样的工作环境最能激发护士的才干和热情以及盖洛普Q12运用在护理人性化管理中对营造一个良好的基层工作环境的作用。方法选用盖洛普Q12调查表，随机抽查某院16个病区的350名护士，采用自设的病人满意度调查表分别调查了这些病区的病人满意度。结果在333份有效问卷中对盖洛普Q12选择“非常满意”的占总选项的39．21％，选择“比较满意”占总选项的41．39％，选择“较不满意”占总选项的5．86％，选择“不满意”占总选项的13．49％，护士满意度和病人满意度有正的直线相关关系，随着护士满意度的提高，病人满意度增高。结论盖洛普Q12运用在护理人性管理中对营造一个积极、高效的基层工作环境是非常有效的，它们是管理中的12个重点。护士长如果能悉心关注这12个方面，使护士们对所有12个问题都作出肯定的回答，那么护士工作的满意度、患者满意度及医院的效益将会得到有效的提高。     

高校图书馆人性化服务的探讨与实践

从人性化服务模式、个性化网络服务、人性化服务环境和图书馆文化中心职能发挥几个方面介绍了高校图书馆提供人性化服务的举措,并针对在人性化服务过程中硬件设施、读者素质、馆员能力3个方面出现的问题提出了相应的措施。     

Tolerability,pharmacokinetics and pharmacodynamics of CMAB001, an anti-CD11a antibody,in Chinese healthy volunteers and psoriatic patients

Aim:

To evaluate the pharmacokinetics (PK), pharmacodynamics (PD) and primary tolerability of an anti-CD11a monoclonal antibody (CMAB001) in Chinese healthy volunteers and psoriatic patients.

Methods:

Two open-label studies were conducted. One was a parallel-group, single-center, dose-escalation test, including 24 healthy adult volunteers from 18 to 45 years in age. All subjects randomly received a single subcutaneous injection dose of 0.5, 1.0 or 2.0 mg/kg. The other was a multiple-dose study: 10 adult psoriatic patients were administered weekly subcutaneous injections of 1.0 mg/kg for 7 weeks.

Results:

CMAB001 was well tolerated in the single- and multiple-dose studies. Slow absorption was observed in both studies. In the single-dose study, the concentration of CMAB001 reached its highest level 2 d later after the injection, and the C_max increased in an approximate dose-proportionate manner, while the area under curve (AUC) showed much greater than dose-proportionate increase. In the multiple-dose study, the steady-state serum concentration level was attained following the 4th injection.

Conclusion:

CMAB001 exhibited a nonlinear pharmacokinetic profile over the dose range from 0.5 to 2.0 mg/kg, and was well tolerated in healthy volunteers and psoriatic patients.     

Drug transporters: Gatekeepers controlling access of xenobiotics to the cellular interior

In this paper, we evaluate methodologies and null mouse models used to study drug transporter function in vitro and in vivo. P-glycoprotein and MRP null mice have been used to examine many aspects of xenobiotic distribution and bioavailability. Their advantage over conventional models is that they allow the exclusion of transporters from a particular process; however, they cannot be used to study the activity of the transporter that has been deleted. Use of humanized mice permits a logical progression from phenomena in wild-type mice via the effects of removing the mouse transporter to the consequences of replacing it with its human counterpart.     

Humoral immune responses in humanized BLT mice immunized with West Nile virus and HIV-1 envelope proteins are largely mediated via human CD5+ B cells

BLT mice, constructed by surgical implantation of human fetal thymus-liver tissues and intravenous delivery of autologous CD34+ haematopoietic stem cells into adult non-obese diabetic/severe combined immunodeficiency mice, were evaluated for vaccine-induced humoral immune responses. Following engraftment, these mice developed a human lymphoid system; however, the majority of the peripheral human B lymphocytes displayed an immature phenotype as evidenced by surface CD10 expression. Over 50% of the human B cells in the periphery but not in the bone marrow also expressed the CD5 antigen, which is found only infrequently on mature follicular B cells in humans. A single intramuscular immunization with recombinant viral envelope antigens, e.g., HIVgp140 and West Nile Virus envelope proteins, together with the immune stimulatory KLK/ODN1a composition) [corrected] adjuvant resulted in seroconversion characterized by antigen-specific human antibodies predominantly of the IgM isotype. However, repeated booster immunizations did not induce secondary immune responses as evidenced by the lack of class switching and specific IgM levels remaining relatively unchanged. Interestingly, the peripheral CD19+ CD5+ but not the CD19+ CD5- human B lymphocytes displayed a late developing CD27+ IgM+ memory phenotype, suggesting that the CD5+ B-cell subset, previously implicated in 'natural antibody' production, may play a role in the vaccine-induced antibody response. Furthermore, human T lymphocytes from these mice demonstrated suboptimal proliferative responses and loss of co-stimulatory surface proteins ex vivo that could be partially reversed with human interleukin-2 and interleukin-7. Therefore, vaccine-induced immune responses in BLT mice resemble a T-cell-independent pathway that can potentially be modulated in vivo by the exogenous delivery of human cytokines/growth factors.     

Pig islet xenograft rejection in a mouse model with an established human immune system

Abstract: Background: Xenotransplantation from pigs provides a potential solution to the severe shortage of human pancreata, but strong immunological rejection prevents its clinical application. A better understanding of the human immune response to pig islets would help develop effective strategies for preventing graft rejection. Methods: We assessed pig islet rejection by human immune cells in humanized mice with a functional human immune system. Humanized mice were prepared by transplantation of human fetal thymus/liver tissues and CD34⁺ fetal liver cells into immunodeficient mice. Islet xenograft survival/rejection was determined by histological analysis of the grafts and measurement of porcine C‐peptide in the sera of the recipients. Results: In untreated humanized mice, adult pig islets were completely rejected by 4 weeks. These mice showed no detectable porcine C‐peptide in the sera, and severe intra‐graft infiltration by human T cells, macrophages, and B cells, as well as deposition of human antibodies. Pig islet rejection was prevented by human T‐cell depletion prior to islet xenotransplantation. Islet xenografts harvested from T‐cell‐depleted humanized mice were functional, and showed no human cell infiltration or antibody deposition. Conclusions: Pig islet rejection in humanized mice is largely T‐cell‐dependent, which is consistent with previous observations in non‐human primates. These humanized mice provide a useful model for the study of human xenoimmune responses in vivo.     

小鼠模型在药物致癌性评价中的应用及研发人源化模型的意义

药物临床前安全性评价中的致癌实验对药物是否能进入临床实验和上市起着至关重要的作用。一些发达国家已经采用小鼠模型的短中期致癌实验作为附加实验，代替了传统的两年期实验。本文主要参考这些模型在致癌实验和药品致癌性评价中的已有数据及资料，对其特点和近年来的应用情况进行了概述。结合现有模型的缺陷，我国新药研发的需求和药物流通日益国际化的现状，得出研发DNA修复系统和细胞周期控制系统缺陷的人源化的转基因模型，是非常有前景的新替代模型。     

Humanized mice for the development and testing of human vaccines

Mouse models of human disease form a link between genetics and biology. However, mice and humans differ in many aspects of immune system biology. These differences might explain, in part, why many successful preclinical immunotherapy studies in mice turn out to be unsuccessful when used in clinical trials in humans. Pioneering studies in the late 1980s demonstrated the reconstitution of human lympho–hematopoietic cells in immunodeficient mice. Since this time, immunodeficient mice are being tested as hosts for human hematopoietic organs or cells in an effort to create an in vivo model of the complete human immune system. Such Humouse models could permit us to generate and test novel human vaccines.     

人源化抗CD3单链抗体在大肠杆菌中的GST融合表达

目的为构建新一代的小分子、高效的基因重组抗CD3/抗胶质瘤双特异性抗体提供一个合适的构件.方法从质粒pZZ3中克隆出人源化抗CD3抗体的VH、VL基因后,构建人源化抗CD3单链抗体基因,将其克隆入表达载体pGEX-5Xl中后转化大肠杆菌,以IPTG诱导表达.结果SDS-PAGE分析表明,表达产物分子量为55kd,与其理论推算值相符.表达形式均以包涵体为主,表达量占菌体总蛋白的30%左右.Westem blot证实,诱导后菌体总蛋白在55kd处出现特异性显色印迹.结论人源化抗CD3单链抗体可以包涵体形式在大肠杆菌中高效表达,为构建人源化双特异性抗体奠定了基础.