Tyrosine kinase inhibitor imatinib (STIS71) as an anticancer agent for solid tumours

Imatinib mesylate, also known as ST1571 or CGP57148, is a competitive inhibitor of a few tyrosine kinases, including BCR-ABL, ABL, KIT, and the platelet-derived growth factor receptors (PDGF-R). It binds to the ATP-binding site of the target kinase and prevents the transfer of phosphate from ATP to the tyrosine residues of various substrates. At oral doses of 300 mg or greater, the vast majority of patients with chronic myeloid leukaemia achieve a haematological response and this is usually associated with limited toxicity. Imatinib also has substantial activity in Philadelphia chromosome-positive acute lymphoblastic leukaemia expressing the BCR-ABL fusion protein. Gastrointestinal stromal tumours (GISTS) have also been evaluated for clinical activity of imatinib. About 90% of malignant GISTs harbour a mutation in c-kit leading to KIT receptor autophosphorylation and ligand-independent activation. According to initial clinical studies, more than 50% of GISTs respond to therapy within a few months, and only about 10-15% progress. The potential for cure and the optimal length of treatment are currently not known. Several other human cancers may over-express KIT or PDGF-R, and clinical trials to evaluate the role of imatinib in the treatment of such cancers are currently ongoing. Imatinib is an example of a specifically designed, highly targeted cancer therapy, which poses novel requirements for both pathology laboratories and clinicians in terms of identifying the major molecular mechanisms involved in tumour growth.     

Umbilical cord stem cell transplantation for primary immunodeficiencies

Primary immunodeficiencies (PIDs) are a rare but important cause of mortality and morbidity in childhood: the most severe – known as severe combined immunodeficiency (SCID) – are fatal within the first year of life; other PIDs are less immediately life-threatening, but have a poor long-term outlook. Haematopoietic stem cell transplantation (HSCT) is the best treatment for SCID and is increasingly offered for other PIDs. The best results are achieved with an HLA-matched family donor. Umbilical cord stem cells (UCSCs) are an alternative stem cell source. Results using UCSCs in the treatment of haematological disorders and malignancy are as good as those for which marrow is the stem cell source. Although PIDs make up a small proportion of disorders amenable to treatment by HSCT, UCSCs are an ideal source of haematopoietic stem cells for many of these patients. Of the 52 patients with SCID or other PIDs for whom detailed information on outcome is available, results of engraftment, immune reconstitution, incidence of graft-versus-host disease and survival are comparable with other stem cell sources. Small stem cell dose and prolonged time to viral immunity limit the patients for whom UCSCs can be used. Newer methods of achieving better engraftment, ex vivo expansion of stem cells and generation of antigen-specific cytotoxic T cells are being developed at present, and will widen the application of UCSCs as a viable source for more patients.     

Dendritic cell maturation in active immunotherapy strategies

Dendritic cells (DCs) loaded with tumour antigen have become the centrepiece of clinical trials testing active immunotherapy strategies. Important variables include the source of DCs, the choice of antigens, the method of antigen loading and the route and timing of administration. Recently, the requirement for and the method of, DC maturation have been receiving particular attention. This is due to observations from in vitro studies and animal models demonstrating that mature DCs induce more potent antigen-specific T-cells responses than immature DCs. Furthermore, preliminary observations in human studies suggest that immature DCs might actually downregulate antigen-specific T-cell responses but mature DCs may augment them. Current studies are addressing how to define DC maturation, whether the variety of methods for maturation result in DCs with similar T-cell stimulatory capacity, how to maintain the maturational status and whether maturation in vitro before immunisation, or in vivo, after immunisation, results in better DC function.     

低频电针足三里对2型糖尿病大鼠糖代谢的影响

目的研究低频电针单侧足三里对2型糖尿病(T2DM)大鼠模型糖代谢的影响,探讨低频电针足三里对T2DM大鼠的疗效机制。方法将30只8周龄雄性Wistar大鼠随机分为空白组10只和造模组20只。造模组造模后将造模成功的16只大鼠随机分为模型组8只和针刺组8只。针刺组予电针单侧足三里治疗,模型组只束缚不干预。比较3组大鼠空腹血糖(FBG)、空腹胰岛素(FI)及定量胰岛素敏感检测指数(QUICKI),观察胰岛β细胞的形态。结果 FBG治疗前与空白组比较,针刺组和模型组均有显著升高(P<0.05),针刺组与模型组比较差异无统计学意义(P>0.05);治疗后与空白组比较,针刺组和模型组均有显著升高(P<0.05),针刺组与模型组比较显著降低(P<0.05)。FI治疗前各组间比较差异均无统计学意义(P>0.05);治疗后各组间比较差异均无统计学意义(P>0.05)。QUICKI治疗前与空白组比较,针刺组和模型组均降低(P<0.05),针刺组与模型组比较差异无统计学意义(P>0.05);治疗后针刺组与空白组比较差异无统计学意义(P>0.05),模型组较空白组降低(P<0.05),针刺组较模型组升高(P<0.05)。在光镜下,针刺组胰腺组织分布均匀度与空白组接近,胰岛结构比较完整,细胞密度略低于空白组,胰岛β细胞胞浆见少量肿胀,纤维组织稍有增生。结论电针足三里能有效控制高糖高脂饮食联合链脲佐菌素(STZ)诱导的T2DM大鼠模型的病情发展,改善胰岛素敏感度及胰岛β细胞的形态。     

The Expression of Calcitonin Gene-related Peptide on the Neurons Associated Zusanli (ST 36) in Rats

Objective:To investigate the biochemical characteristic of the neurons associated Zusanli(ST 36)in the rat by using Alexa Fluor 594 conjugated cholera toxin subunit B(AF594-CTB)neural tracing and calcitonin gene-related peptide(CGRP)fluorescent immunohistochemical techniques.Methods:Four male Sprague Dawley rats were injected with AF594-CTB into the corresponding area of the Zusanli in the human body.After 3 surviving days,the rat's spinal cord and dorsal root ganglia(DRGs)at lumbar segments were dissected following perfusion with 4%paraformaldehyde,cut into sections,and then stained with CGRPfluorescent immunohistochemical method.Results:AF594-CTB labeled sensory neurons were detected in the L3-L6 DRGs with high concentration in L4 DRG,and the labeled motor neurons located in the dorsolateral and intermediate regions of laminaⅨfrom L3-L5 segments with high concentration at L4.Meanwhile,CGRPpositive neural labeling distributed symmetrically on both sides of DRGs,anterior and dorsal homs of spinal cord.In the AF594-CTB labeled neurons,37%sensory neurons and 100%motor neurons expressed CGRPpositive.Conclusion:These findings present the morphological evidence to demonstrate that the sensory and motor neurons associated Zusanli in the rat distributed with segmental and regional patterns,and contained CGRP-expression.     

急性ST段抬高型心肌梗死患者再灌注治疗预后的影响因素

【摘要】 目的 探讨急性ST段抬高型心肌梗死（STEMI）患者再灌注治疗预后的影响因素。方法 选取2012年1月～2015年1月于我院行再灌注治疗的126例STEMI患者作为研究对象,采用回顾性分析所有患者的临床及随访资料,根据其资料结果记录所有患者的性别、年龄、疾病史等一般临床资料,疾病情况、血红蛋白等相关临床指标水平以及再灌注治疗后的预后效果,并比较不同预后效果患者间上述资料的差异性。分析影响再灌注治疗STEMI患者预后的因素。结果 126例STEMI患者经再灌注治疗后预后好106例(8413%),预后差20例(1587%); 年龄≥60岁的STEMI患者其女性和糖尿病比例以及心功能killip分级较高,而吸烟和饮酒患者较少,血红蛋白水平较低,预后较差（P＜005）;中、重度贫血患者其女性、吸烟、糖尿病比例和年龄及心功能能killip分级均高于非贫血和轻度贫血者,且前两者预后更差比较差异间均具有统计学意义（P＜005）;既往存在糖尿病病史,有吸烟、喝酒习惯,心功能killip分级过高、血脂异常以及年龄≥60岁和中、重度贫血的STEMI患者经再灌注治疗后其预后较差（P＜005）;经非条件多因素Lgistic回归模型分析显示,killip分级过高、血脂异常以及年龄≥60岁和中、重度贫血是影响STEMI再灌注治疗预后效果的独立危险因素（P＜005）。结论 STEMI患者经再灌注治疗后的预后效果尚可,年龄≥60岁和中、重度贫血等均为影响STEMI再灌注治疗预后效果的独立危险因素,可将其联合作为临床上评估STEMI患者经再灌注治疗预后效果的有效指标。     

艾灸改善非小细胞肺癌化疗期间胃肠道不良反应临床研究

目的:观察艾灸防治非小细胞肺癌患者化疗期间胃肠道不良反应的临床疗效。方法:将50例非小细胞肺癌患者随机分为对照组和治疗组,每组各25例。对照组采用TP方案化疗,治疗组在对照组的基础上艾灸神阙穴与双侧足三里穴。观察两组患者化疗后恶心、呕吐的发生情况。结果:治疗组有效率明显高于对照组,差异有统计学意义(P0.05)。结论:艾灸对化疗所致消化道不良反应具有一定的防治作用,且操作方便、安全性高、经济实惠。     

免疫分选软骨前体细胞并诱导永生化的研究

目的建立永生化大鼠软骨前体细胞株,为细胞移植和转基因治疗提供稳定的细胞来源。方法利用免疫磁珠技术分离纯化具有特异性表面标志成纤维生长因子受体-3(FGFR-3)的软骨前体细胞,用基因转染技术将含有猿肾病毒40大T抗原基因(SV40Tag)的重组质粒pEGFP- IRES2-SV40Tag转染原代培养的新生大鼠软骨前体细胞,经G418筛选,抗性克隆扩大培养。应用FGFR-3、Ⅱ型胶原和X型胶原抗体进行细胞鉴定,检测其分化能力,观察细胞的形态及其生长状况,绘制生长曲线。用逆转录-聚合酶链反应(RT-PCR)、Southern blot和免疫细胞化学法鉴定SV40Tag在转染细胞中的表达。结果获得1个阳性细胞克隆,免疫细胞化学证实为FGFR-3阳性的具有较强增值能力和多分化潜能的软骨前体细胞。经Southern印迹杂交证实,SV40Tag已稳定转染入软骨前体细胞,表达mRNA及其蛋白。贴壁培养的永生化软骨前体细胞株(IPSC),群体倍增时间为23.62 h,传代、冻存和复苏对细胞形态及生长无明显影响。结论SV40Tag导入可诱导软骨前体细胞永生化,为软骨前体细胞的实验研究及其介导的细胞移植治疗提供了稳定的细胞来源。