二甲双胍在皮肤病治疗中的应用进展

二甲双胍通过抑制肝脏葡萄糖输出、改善外周组织对胰岛素的敏感性、增加肌肉及脂肪细胞对葡萄糖的摄取和利用而发挥降糖作用,已是临床广泛应用的口服降糖药,被欧洲糖尿病研究学会（EASD）及美国糖尿病协会（ADA）等颁布的国际指南推荐为2型糖尿病（T2DM）的一线治疗药物。除降糖作用外,二甲双胍还具有降血脂、抗血小板聚集及抗氧化效应,并能降低癌症发病风险及死亡率［１］。此外,二甲双胍可以延长实验室动物和秀丽隐杆线虫的寿命［2］,刺激神经生成［3］,减轻庆大霉素的肾毒性［4］及甲氨蝶呤的肝毒性［5］。在皮肤科,二甲双胍对多毛症、痤疮、反向性痤疮、黑棘皮病、银屑病及皮肤肿瘤等疾病也有治疗作用……     

基于问题学习教学法结合传统教学法在血管神经病学教学中的应用

目的 总结基于问题学习 （problem-based learning, PBL） 教学法结合传统教学法 （lesson-based learning, LBL） 在医学生临床学习中的作用。 方法 对2011年-2014年在首都医科大学附属北京天坛医院神经内科进行临床学习的7年制医学生, 采用PBL结合LBL的教学模式, 教学后对学生进行问卷调查, 统计学生对教学方法的意见。 结果 共发放并收回合格问卷200份, 统计显示学生对PBL结合LBL的教学模式在激发学习兴趣, 加 深对理论知识的理解, 拓展临床逻辑思维能力、 提高分析解决问题的能力, 理论联系实际能力、 提高 独立思考能力、 提高沟通协作能力等方面认可度较高 （84.3%～92.3%） , 85.3%的学生认为有必要继 续采用这种教学方法。 结论 医学生对PBL结合LBL的临床教学模式的接受度较高, 有利于提高学生的学习积极性。     

新生儿缺氧缺血性脑病血谷胱甘肽过氧化物酶水平与DNA损伤的关系探讨

目的探讨新生儿缺氧缺血性脑病(HIE)血液中谷胱甘肽过氧化物酶(GSHPx)水平与外周血单个核细胞DNA损伤程度的关系。方法HIE患儿20例,分别在急性期、恢复期采血,用动力学检测全血中GSHPx水平,用碱性单细胞凝胶电泳(SCGE)检测外周血中单个核细胞的彗星率及尾矩。12例新生儿作为正常对照组。结果急性期HIE患儿血中,GSHPx水平明显减低,与对照组比较有统计学意义(P<0.01),恢复期GSHPx水平上升,与对照组比较无统计学意义(P>0.05);急性期HIE患儿外周血单个核细胞彗星率及尾矩显著增高,与对照组比较有统计学意义(P<0.01),恢复期两者水平下降,但与对照组比较仍有统计学意义(P<0.01)。结论自由基及DNA损伤参与了新生儿HIE的病理发展过程,GSHPx可作为HIE患儿体内自由基水平检测指标之一。     

胰岛素样生长因子在常染色体显性遗传性多囊肾病发病中的作用

目的:研究胰岛素样生长因子1(insulin-likegrowth factor-1,IGF-1)在常染色体显性遗传性多囊肾病(autosomaldominant polycystic kidney disease,ADPKD)发病中的作用.方法:采用酶联免疫吸附法测定41例ADPKD患者血液、囊肿液及尿液中IGF-1浓度;应用免疫组织化学染色方法检测IGF-1及其受体(IGF-1R)在ADPKD囊肿组织中的表达.结果:41例ADPKD患者囊肿液中的IGF-1浓度(1 62.0±5.06)ng/ml显著高于血液(76.0±28.13)ng/ml和尿液(62.0±11.18)ng/ml中浓度(P＜0.01);IGF-1和IGF-1R在ADPKD囊肿组织中的囊肿衬里上皮细胞、平滑肌细胞及间质细胞均呈阳性表达.结论:囊肿液中IGF-1的增多可能来自囊肿衬里上皮细胞及间质细胞的合成和分泌,并与囊肿的形成和长大有关.     

基于解决问题学习法的中药学教学方法

结合作者在中药学PBL教学中多年的体会,阐述了PBL在中药学总论、各论、实训课及案例教学等多个环节的应用,指出通过PBL有助于强化学生对总论部分中药学基本理论、各论部分章节概述部分的共性及具体药物的个性特征的认识,有助于通过实训课对中药饮片外观及内在特征的认识,还有助于学生将所学的具体中药与模拟临床相结合学以致用.     

Signaling mechanism of cell adhesion molecules in breast cancer metastasis: potential therapeutic targets

Metastasis is responsible for the majority of breast cancer-related deaths. The metastatic spread of cancer cells is a complicated process that requires considerable flexibility in the adhesive properties of both tumor cells and other interacting cells. Cell adhesion molecules (CAMs) are membrane receptors that mediate cell–cell and cell–matrix interactions, and are essential for transducing intracellular signals responsible for adhesion, migration, invasion, angiogensis, and organ-specific metastasis. This review will discuss the recent advances in our understanding on the biological functions, signaling mechanisms, and therapeutic potentials of important CAMs involved in breast cancer metastasis.     

Risk of aggressive breast cancer in women of Han nationality carrying TGFB1 rs1982073 C allele and FGFR2 rs1219648 G allele in North China

The high morbidity and aggressive behavior of breast cancer are associated with genetic variations. Single nucleotide polymorphisms (SNPs) in many genes have been demonstrated as a risk factor for breast cancer. In this study, we evaluated the association of the SNP rs1982073 (Leu10Pro) in transforming growth factor-beta 1 (TGFB1) gene and the SNP rs1219648 in fibroblast growth factor receptor 2 (FGFR2) gene with the risk and aggressiveness of breast cancer among women of Han nationality in North China. TaqMan allelic discrimination assay was performed to genotype rs1982073 and rs1219648 in 447 breast cancer cases and 406 age-matched healthy controls. The results imply that genotype frequencies of rs1982073 and rs1219648 were not significantly different between breast cancer patients and healthy controls. However, for TGFB1 SNP rs1982073, the C-carriers (T/C+C/C genotype) were more likely to bear tumors of greater aggressiveness (histological grade III) than T/T-carriers (grade I–II) (OR = 3.45, 95% CI: 1.48–8.00, P = 0.004). For FGFR2 SNP rs1219648, G-carriers (A/G+G/G genotype) were more significantly linked to tumors with lymph node metastasis than those with A/A genotype (lymph node negative) (OR = 1.69, 95% CI: 1.11–2.58, P = 0.016). Therefore, the SNPs of TGFB1 rs1982073 and FGFR2 rs1219648 may contribute to the identification of patients with more aggressive breast cancers among Han women in North China.     

Mucosal memory CD8⁺ T cells are selected in the periphery by an MHC class I molecule

The presence of immune memory at pathogen-entry sites is a prerequisite for protection. Nevertheless, the mechanisms that warrant immunity at peripheral interfaces are not understood. Here we show that the nonclassical major histocompatibility complex (MHC) class I molecule thymus leukemia antigen (TL), induced on dendritic cells interacting with CD8αα on activated CD8αβ(+) T cells, mediated affinity-based selection of memory precursor cells. Furthermore, constitutive expression of TL on epithelial cells led to continued selection of mature CD8αβ(+) memory T cells. The memory process driven by TL and CD8αα was essential for the generation of CD8αβ(+) memory T cells in the intestine and the accumulation of highly antigen-sensitive CD8αβ(+) memory T cells that form the first line of defense at the largest entry port for pathogens.     

Autocrine IL-2 is required for secondary population expansion of CD8(+) memory T cells

Two competing theories have been put forward to explain the role of CD4(+) T cells in priming CD8(+) memory T cells: one proposes paracrine secretion of interleukin 2 (IL-2); the other proposes the activation of antigen-presenting cells (APCs) via the costimulatory molecule CD40 and its ligand CD40L. We investigated the requirement for IL-2 by the relevant three cell types in vivo and found that CD8(+) T cells, rather than CD4(+) T cells or dendritic cells (DCs), produced the IL-2 necessary for CD8(+) T cell memory. Il2(-/-) CD4(+) T cells were able to provide help only if their ability to transmit signals via CD40L was intact. Our findings reconcile contradictory elements implicit in each model noted above by showing that CD4(+) T cells activate APCs through a CD40L-dependent mechanism to enable autocrine production of IL-2 in CD8(+) memory T cells.     

重视教学方法,提高神经病学临床实习效果

由于神经病学的特殊性,临床实习有其自身的特点,如何提高神经病学实习效果也成为临床带教教师关注的热点之一。本研究从"加强教师素质建设,教书育人;加强医学模拟教学模式的建设;开展启发式教学,培养实习生的创新能力;加强医学生的医德素质和法律意识培养,构建和谐的医患互信体系"等方面,提出了在医学模式转变的情形下,提高神经病学临床实习质量的方法。