参芎注射液对腹膜透析患者转化生长因子β1的影响

目的观察参芎注射液对腹膜透析患者转化生长因子β1(TGFβ1)及腹膜功能的影响。方法选择2012年12月至2014年5月我院肾内科进行腹膜透析的60例患者,随机分为2组:常规腹膜透析组(对照组)和参芎注射液腹膜透析组(观察组),每组30例。比较两组相关临床和生化指标,应用ELISA法检测TGFβ1表达。结果治疗前,两组肌酐透析液与血浓度之比(D/Pcr)、尿素清除指数(KT/V)、肌酐清除率(Ccr)、尿量和超滤量比较差异无统计学意义(P>0.05)。治疗后,对照组上述指标无显著变化(P>0.05);观察组D/Pcr、KT/V、Ccr、尿量与治疗前比较差异无统计学意义(P>0.05),但超滤量升高(P<0.01)。两组血浆白蛋白(ALB)、钙(Ca)、磷(P)、甲状旁腺素(iP TH)在治疗前、后比较差异均无统计学意义(P>0.05)。治疗前,两组TGFβ1表达水平比较差异无统计学意义(P>0.05);治疗后,对照组TGFβ1表达无显著变化(P>0.05),但观察组显著减低(P<0.01)。结论参芎注射液可显著提高腹透患者的超滤量,抑制腹膜细胞的TGFβ1分泌,具有抗腹膜纤维化的功效。     

Human Antibody Fragments Specific for the Epidermal Growth Factor Receptor Selected from Large Non-immunised Phage Display Libraries

Antibodies to EGFR have been shown to display anti-tumour effects mediated in part by inhibition of cellular proliferation and angiogenesis, and by enhancement of apoptosis. Humanised antibodies are preferred for clinical use to reduce complications with HAMA and HAHA responses frequently seen with murine and chimaeric antibodies. We have used depletion and subtractive selection strategies on cells expressing the EGFR to sample two large antibody fragment phage display libraries for the presence of human antibodies which are specific for the EGFR. Four Fab fragments and six scFv fragments were identified, with affinities of up to 2.2 nM as determined by BIAcore analysis using global fitting of the binding curves to obtain the individual rate constants (k_a and k_d). This overall approach offers a generic screening method for the identification of growth factor specific antibodies and antibody fragments from large expression libraries and has potential for the rapid development of new therapeutic and diagnostic reagents.     

SH-SY5Y神经细胞中α7神经型尼古丁受体基因沉默对CaM、CaMKⅡ蛋白水平的影响

目的构建稳定的α7 n AChR沉默的神经母细胞瘤细胞(SH-SY5Y)细胞,研究α7神经型尼古丁受体(n AChR)基因沉默对钙调蛋白(Ca M)、钙调素依赖性蛋白激酶Ⅱ(Ca MKⅡ)水平的影响,了解α7 n AChR神经保护作用及其与阿尔茨海默病(AD)发病机制的关系。方法将α7 n AChR shRNA重组质转染到SH-SY5Y,用含嘌呤霉素的培养液筛选,挑选阳性克隆后采用实时荧光定量PCR和蛋白质印迹方法(Western-blot)检测细胞中α7n AChR mRNA及蛋白表达水平的变化;Western-blot方法测定Ca M、Ca MKⅡ蛋白表达水平。结果获得稳定转染α7 n AChR shRNA重组质粒的细胞克隆株,与对照组相比,α7 n AChR mRNA及蛋白表达量分别减少了95%和80%。Ca M、Ca MKⅡ蛋白表达量分别减少了48.5%和35%。结论成功构建了α7 n AChR mRNA沉默的SH-SY5Y细胞细胞株,α7 n AChR沉默降低了Ca M、Ca MKⅡ的蛋白水平,可能影响信号通路转导,这可能与阿尔茨海默病(AD)的发病有一定的关系。     

A REPORT OF 8 CASES WITH HEMOGLOBIN H DISEASE IN AN IRANIAN FAMILY

α-Thalassemia is a common genetic disorder in Iran. However, no comprehensive data on epidemiology of severe forms of α-thalassemia, including hemoglobin H (HbH) or hydrops fetalis, is available in this population. This is a first case report of an Iranian family with large number of HbH individuals. The proband is a 48-year-old woman, referred to our center with anemia and no history of previous blood transfusions. Similar clinical phenotype has been observed in all of her 5 siblings, 2 of her 4 children, and her granddaughter, whose parents are first cousins. A reverse hybridization assay covering 21 α globin mutations was performed to determine the genotype in 11 members of this family and a fetus. HbH genotype was identified in 9 individuals, representing 3 generations, including a fetus. The high prevalence of α-thalassemia carriers together with the high rate of consanguineous marriages could lead to a large number of individuals with HbH or even hydrops fetalis in Iranian families. Therefore, to avoid the risk of having affected offspring, carrier detection, genetic counseling, and prenatal diagnosis would be of vital importance for individuals with low red blood cell (RBC) indices, normal iron status, and normal HbA₂ level, who are suspected to be α-thalassemia carriers.     

α2b干扰素联合利巴韦林气雾剂治疗手足口病

目的探讨α2b干扰素联合利巴韦林气雾剂治疗手足口病的疗效和安全性。方法将80例手足口病患者随机分为治疗组和对照组,每组各40例。治疗组采用肌注α2b干扰素加利巴韦林气雾剂喷雾吸入治疗,对照组采用静脉滴注利巴韦林再联合蒙脱石散涂布口腔,然后对两组的治疗效果进行比较。结果治疗组的有效率是87.5%,对照组的有效率是62.5%,两组比较,差异有统计学意义(P<0.05);治疗组在退热时间、口腔溃疡愈合时间及进食时间方面比对照组有明显的优势。结论α2b干扰素联合利巴韦林气雾剂治疗手足口病有显著的疗效,并且安全可靠,没有明显不良反应。     

Smad蛋白研究进展

Smad蛋白家族是转化生长因子β（TGFβs）超家族重要的细胞因子，共同担负着调节细胞生长、分化、凋亡等过程，主要由8种不同的蛋白构成整个Smad家族，通过可逆磷酸化对多种信号传导通路的功能起着荚键的调节作用，分别行使兴奋和抑制等不同作用。本文对Smad蛋白调节作用机制进行综述。     

Nicotine contributes to the neural stem cells fate against toxicity of microglial-derived factors induced by Aβ via the Wnt/β-catenin pathway

Recent studies have demonstrated that the molecules secreted from microglias play important roles in the cell fate determination of neural stem cells (NSCs), and nicotinic acetylcholine receptor agonist treatment could reduce neuroinflammation in some neurodegenerative disease models, such as Alzheimer's disease (AD). However, it is not clear how nicotine plays a neuroprotective role in inflammation-mediated central nervous diseases, and its possible mechanisms in the process remain largely elusive. The aim of this study is to improve the survival microenvironment of NSCs co-cultured with microglias in vitro by weakening inflammation that mediated by accumulation of β-amyloid peptide (Aβ). The viability, proliferation, differentiation, apoptosis of NSCs and underlying mechanisms associated with Wnt signaling pathway were investigated. The results showed that Aβ could directly damage NSCs. Furthermore, concomitant to elevated levels of TNF-α, IL-1β derived from microglias, the NSCs had been damaged more severely with the upregulation of Axin 2, p-β-catenin and the downregulation of β-catenin, p-GSK-3β, microtubule-associated protein-2, choline acetyltransferase. However, addition of 10 μmol/L nicotine before microglias treated with Aβ was beneficial to protect the NSCs against neurotoxicity of microglial-derived factors induced by Aβ, which partially rescued proliferation, differentiation and inhibited apoptosis of NSCs via activation of Wnt/β-catenin pathway. Taken together, these data imply that low concentration nicotine attenuates NSCs injury induced by microglial-derived factors via Wnt signaling pathway. Thus, treatment with nicotinic acetylcholine receptor agonist provides a promising research field for neural stem cell fate and therapeutic intervention in neuroinflammation diseases.     

调控TGFβ1/SMAD通路的microRNAs在失神经支配骨骼肌中的表达

目的:本研究拟探讨骨骼肌失神经支配后差异性表达的microRNAs,并明确其是否参与调控TGFβ1/SMAD信号通路。方法:C57/BL6J小鼠,随机分为正常对照组和实验组,实验组小鼠切断右下肢坐骨神经为手术组,左下肢游离坐骨神经作为假手术组。4周后处死小鼠取腓肠肌Masson染色观察肌纤维形态变化,比较各组肌纤维横截面积。以TGFβ1/SMAD为靶基因,通过生物信息学分析寻找到18个可能的miRNAs指标。定量PCR检测其表达,并针对表达升高的microRNAs采用荧光素酶报告基因实验确认其靶基因。结果:手术组肌纤维横截面积比对照组明显缩小,对照组与假手术组肌肉之间的差异无统计学意义。在失神经骨骼肌中特异性高表达的有miR-424、miR-744、miR-15a。在C2C12细胞系中行报告基因实验显示,与对照组比较,转染miR-744后,SMAD3的荧光素酶强度下降;转染miR-15a后,TGFβ1的荧光素酶强度下降;转染miR-424后,SMAD3的荧光素酶强度变化无统计学意义。PCR验证microRNAs的靶基因显示,转染miR-744、miR-15a的模拟物后,分别对应的SMAD3、TGFβ1表达下调,差异有统计学意义。结论:miR-424、miR-744、miR-15a可能参与调控失神经支配导致的骨骼肌萎缩纤维化,其中miR-744的靶基因是SMAD3,miR-15a的靶基因是TGFβ1。