Application of Aptamers in Biomedicine

Corresponding author e-mail:[email protected]; [email protected][中文文摘]核酸适体是经配体指数富集系统进化技术(SELEX)筛选获得的一类能够特异性地结合离子、分子,甚至整个细胞的单链DNA或者RNA分子。本文介绍了核酸适体及相关筛选技术SELEX;综述了近年来以提高筛选效率和效果为目标的核酸适体筛选技术新进展;列举了核酸适体在无机离子、小分子、生物大分子和肿瘤细胞检测、肿瘤标记物的发现等方面的应用;讨论了基于核酸适体的靶向治疗策略;最后对核酸适体在生物医学上的应用前景进行了展望。[英文文摘]Aptamers are a new class of nucleic acid probes,which are ssDNA /RNA molecules selected to target a wide range of ions,molecules and even cells through SELEX(systematic evolution of ligands by exponential enrichment) technique.This paper presents aptamers and traditional selection approaches;summarizes recent efforts in developing new aptamer selection strategies;reviews new approaches for biomedical analysis,disease biomarker discovery and target therapy.Finally,the potential of aptamers in biomedicine is also discussed.国家重点基础研究发展计划(973)项目(No.2010CB732400); 福建省自然科学基金项目(No.2008J0107)资

Experimental study on reperfusion of intraocular lens

作者简介: 祁明信, 男, 1945 年7 月 出生, 教授、主任医师、博士研究生 导师, 主要从事白内障的基础与临 床研究。联系电话: 0591-83570887; E-mail:qihuang@netease. com 通讯作者: 黄秀榕,E-mail:[email protected][中文文摘]目的开展晶状体再灌注的离体和动物实验研究,并对再灌注人工晶状体技术进行评价。方法采用新鲜离体幼兔眼、离体猪眼、新西兰白兔眼,应用自行研制的人工晶状体材料,进行以下实验:(1)体外固化实验;(2)晶状体前囊膜微型撕囊及其稳固性实验;(3)经微型前囊膜开口超声乳化吸出晶状体内容物实验;(4)活的新西兰白兔眼内人工晶状体再灌注实验。结果(1)按硅酮聚合物与固化剂50:1的比例可获得柔软、弹性好、固化时间短(完全固化时间为60min)的注入材料;(2)晶状体前囊膜1.8～2.0mm的连续环形撕囊口具有较好的稳定性,可经该微型开口吸出晶状体内容物并灌注材料;(3)超声能量18%、流量25mL·min-1、负压120mmHg(1kPa=7.5mmHg)为晶状体内容物经微型前囊膜开口吸出的最佳条件;(4)注入灌注材料后可形成由晶状体囊膜包裹的、置换原晶状体皮质和核的、新的再灌注人工晶状体。结论采用再灌注人工晶状体的方法可进行新型人工晶状体再灌注,可为治疗白内障和老视提供参考。[英文文摘]Objective To carry out the experimental study on reperfusion of intraocular lens(IOLs) in vitro or in animal,and to assess the technique of IOLs reperfusion.Methods The following experiments were performed by using self-developed materials in fresh rabbit eyes and pig eyes in vitro,as well as in eyes of alive New-Zea-land rabbits:(1)Solidification study of self-developed material in vitro;(2)Continuous circular capsulorhexis(CCC) in anterior capsule of lens and its stability;(3)Draw of lens contents via phaco through mini-CCC;(4)IOLs ref illing in the eyes of alive New-Zea land rabbits. Results(1) Thematerialwhich was soft, springy and short-term solidification(full solidification time was 60 minutes) were obtained in certain proportion of geland solidified agent(50:1) in vitro; ( 2)The CCC in anterior capsule of lens with 1.8-2.0 mm diameter had very good stability. The lens contents were drawn and the materialwere refilled through themini-CCC; (3) The best conditions of drawing out lens contents through m ini-CCC were phaco energy 18% , flow 25 mL·min- 1, and negative pressure 120 mmH g (1kPa=7.5 mmHg);(4) The new refilled IOLs, which were wrapped by capsule of lens and were replaced original cortex and nucleus of lens, were obtained after thematerial refillied. Conc lusion. New IOLs are refilled through this method, which can prov ide reference for the treatment of cataract and presbyopia.福建省科技三项费用;教育厅重点资助项目基金资助(编号:K98041

胰岛素降低海马谷氨酸及-Ｄ-丝氨酸含量改善糖尿病大鼠空间学习记忆能力

目的　观察胰岛素对糖尿病大鼠空间学习记忆及海马组织中谷氨酸、Ｄ-丝氨酸含量的影响。方法　采用尾静脉注射链脲佐菌素（ＳＴＺ）制备大鼠糖尿病（ＤＭ）模型。注射ＳＴＺ第３天模型成功后，每天 １次 ｓｃ给予胰岛素 ２Ｕ·ｋｇ－１，持续 ８２ｄ。定期检测各组动物体重及空腹血糖。造模 １１周后进行 Ｍｏｒｒｉｓ水迷宫实验，检测大鼠学习记忆能力；实验结束后取海马组织，观察形态变化，并测定谷氨酸及 Ｄ-丝氨酸含量。结果　与正常对照组比较，ＤＭ模型组大鼠体重明显减轻（Ｐ＜０．０１），血糖明显升高（Ｐ＜０．０１），逃避潜伏期明显延长及原平台象限游泳时间显著减少（Ｐ＜０．０１），海马组织中谷氨酸及Ｄ-丝氨酸的含量均显著升高（Ｐ＜０．０１）。胰岛素治疗组体重增加、血糖含量恢复到正常水平。与 ＤＭ模型组相比，胰岛素治疗组大鼠逃避潜伏期显著缩短（Ｐ＜０．０１），原平台象限游泳时间占总时间百分比显著增加（Ｐ＜０．０１）；海马组织中谷氨酸及Ｄ-丝氨酸的含量也分别由 ＤＭ模型组的（１．５５０±０．０５４）和（０．０８４±０．０５）ｍｇ·ｇ－１下降为胰岛素治疗组的（１．１３７±０．０２３）和（０．０６８±０．００４）ｍｇ·ｇ－１。结论　胰岛素可以改善糖尿病大鼠空间学习记忆能力，这可能与其降低海马组织中谷氨酸及Ｄ-丝氨酸的含量有关

冰冻雨雪灾害对江西林业影响的评估技术探讨

2008年初南方发生了持续冰冻雨雪灾害天气,造成了重大的经济损失。论文以江西林业在雪灾中的受损情况为研究实例,基于GIS、RS技术,在多数据源的支持下,阐释灾害评估的新技术研究方法与处理流程,快速地对江西林业受损情况做出相对精确的评估。根据MODIS提取出的雪灾前后的NDVI变化情况,同时利用多源土地利用数据进行融合处理获取江西植被分布数据,进一步结合研究区的DEM数据,利用GIS提供的叠合处理分析工具得出NDVI变化与树种林型、地形高程、坡度、坡向等各个因素的关系。文章最后根据上述分析结果,提出了灾后重建建议及对GIS、RS技术的结合应用提出展望

医院文书档案管理问题研究[J]

文书档案是医院档案重要组成部分，也是医院档案资源体系建设的重要构成部分，文书档案是保存医院历史发展真实轨迹的原始史料。文书档案工作做好了，医院整个发展历史可根据需要活生生地展示在人们的眼前，将重现历史发展的当时画面。没有文书档案的医院就是一所没有历史的医院。可见文书档案管理的好坏，对医院是否有其发展历史具有十分重要的作用，必须引起医院领导层的高度重视。采取有效措施改变医院目前文书档案管理存在的不足，提升管理水平

Construction and Identification of siRNA Targeting to Multidrug Resistance Gene 1

通信作者:[email protected][中文文摘]mdr1基因及其表达产物P-gp是引起肿瘤细胞多药耐药(MDR)的主要原因,抑制mdr1基因的表达可用于逆转MDR.RNAi可用于特异抑制靶基因的表达,本研究的目的是构建获得可特异有效靶向mdr1基因的siRNA元件.应用siRNA设计软件与mRNA结构分析软件设计构建了3个分别靶向mdr1基因mRNA环结构和茎结构的siRNA元件,同时构建了携带mdr1基因序列的luc报告质粒,通过siRNA表达质粒与携带靶序列的报告质粒的共转染抑制实验检测不同siRNA的抑制效率,结果显示靶向环结构siMDR1B具有较好的抑制效率和特异性.进一步将siMDR1B表达载体与mdr1基因表达载体共转染细胞,应用免疫流式细胞术检测显示,相比对照细胞,siMDR1B可显著抑制其转染后mdr1基因产物P-gp蛋白的表达活性.同时采用CCK-8细胞活性检测试剂评价了siMDR1B对细胞活性的影响,结果显示siMDR1B不会影响细胞活性,具有良好的特异性.本研究获得的可有效靶向mdr1基因的siRNA元件可为进一步开展逆转MDR研究提供重要基础.[英文文摘]The over-expression of mdr1 gene is the main reason of multidrug resistance(MDR) of tumor cells.Inhibiting the expression of mdr1 gene can be used to reverse the MDR.RNA interfence(RNAi) is a sequence-specific intracellular mechanism of gene silence.In this study,the construction of small interfering RNAs(siRNAs) element against mdr1 gene effectively and specifically were explored.Three siRNA sequences targeting to mRNA stem or loop stucture separately were selected based on the sequence of mdr1 gene.Using various reporter plasmids contaiining different target sequences,the inhibition efficiencies and specificities of the constructs against mdrlgene were determined and siMDR1Btargeting to the loop structure was selected from the candidates.siMDR1B expression vector was then co-transfected with the mdrigene expression vector in cells,and the expression level of P-gp protein encoded by mdr1gene was analysed by immune flow cytometry.Results showed that P-gp protein expression can be effectively inhibited by siMDR1Bin transformed cells comparing to control cells.CCK-8assay was used for cell viablity analsis in this study,and results showed that cell viability was not affected by siMDR1Bexpression in transformed cells.In conclusion,siMDR1Bis a promising candidate for the next research on MDR reverse.福建省卫生厅青年科研课题计划项目(2008-1-53); 厦门市卫生局基金项目(3502z20089012

Research progress on pathogenesis of renal fibrosis in patients with diabetic nephropathy

综述了国外在糖尿病重要并发症糖尿病肾病的肾纤维化病变发病机制方面的最新进展,指出多元醇糖代谢支路与醛糖还原酶的异常激活、转化生长因子-β(TGF-β)/Smad信号转导途径的异常激活可能是糖尿病肾病肾脏炎症和肾纤维化病变的主要机制,此外,miR-NAs也可能通过影响TGF-β信号转导途径达到影响糖尿病肾病肾纤维化病变进程的作用。[英文文摘]It reviewed the foreign latest progress on the pathogenesis of renal fibrosis lesions in diabetic nephropathy of important diabetic complications.And it pointed out that abnormal polyhydric alcohol sugar metabolism branch and abnormal activation of aldose reductase，abnormal activation of TGF-β/Smad signal transduction pathways may be main mechanisms of kidney inflammation in diabetic nephropathy and renal fibrosis lesions.In addition,miRNAs may also influence the renal fibrosis process in diabetic nephropathy through impacting the TGF-βsignal transduction pathways.国家973项目资助,编号:2009CB9416010;国家自然科学基金,编号:30970649;福建省科研基金资助,编号:2010L0002;厦门大学细胞应激生物学国家重点实验室开放课题基金;细胞生物学与肿瘤细胞工程教育部重点实验室访问学者基金资

Differential Proteomic Analysis of Endometriosis in Mouse

通信作者:[email protected][中文文摘]利用所构建的BALB/c小鼠子宫内膜异位症(EMs)模型,通过对正常和EMs小鼠在位子宫内膜样品双向电泳图谱的比较,找到61个差异较明显的蛋白质斑点,结合质谱分析技术和数据库信息检索最终鉴定出23个蛋白,包括11个调控蛋白、4个信号转导相关蛋白、1个代谢相关蛋白、5个膜联蛋白、1个细胞骨架蛋白和1个RNA解旋酶.将蛋白质组学技术应用于EMs的研究,可以从分子水平探索EMs的发病机理,对EMs的诊断及治疗具有重要意义.本研究结果为进一步探索EMs发病机理提供实验基础,同时也为寻找该病早期诊断的标志物和治疗的靶点提供理论依据.[英文文摘]Based on the established endometriosis BALB/c mice model,the differential expression of eutopic endomereium proteins from the normal and endometriosis mice were compared by two-dimensional electrophoresis.There are 61 spots of significant differential proteins to be found.Among them,23 protein-spots were identified by mass spectrometry.They were 11 kinds of regulation-related proteins,4 kinds of signal transduction-related proteins,1 kind of metabolism-related proteins,5 kinds of membrane associated proteins,1 kinds of cyskeletal proteins and 1 kinds of RNA helicase enzymes,respectively.The application of proteomics in EMs research would be important for the study of the mechanism and should be significant in the diagnosis and treatment of the disease.The results would provide a theory foundation for studying the pathogenesis of endometrosis and some academic thereunder for searching early diagnosisi marker and therapeutic target.国家基础科学人才培养基金项目(J1030626); 福建省医学创新课题资助计划项目(2009-CXB-49); 厦门市科技计划医疗卫生项目(3502Z20084006

Classification Model of Hepatitis B Virus Patients and Healthic People Established from Mass Spectrometric Data

朱尔一，E-mail:[email protected][中文文摘]建立运用表面加强激光解吸电离-飞行时间质谱获取乙肝病人和健康人血清蛋白指纹图谱数据,并用偏最小二乘(PLS)变量筛选法建立乙型肝炎(HBV)病人和健康人的分类模型,最终得到分类模型的交叉检验相关系数达0.97以上,判别准确率显著提高。对模型进行分析,找出对乙型肝炎病人和健康人的差异有重要影响的因素或变量。这些变量为某些质荷比区间内特定蛋白的峰强度值,反映这些质荷比区间内蛋白量的增加或减少,与乙肝病的形成有密切关系,可作为重要的生物标志物,进一步加以研究。本研究采用所得模型的拟合值等一些信息来做分类图,能较好地表达回归模型的分类效果。［英文文摘］Classification models of hepatitis B virus(HBV)patients and healthy people have been built from mass spectrometric data,which can be used for the detection of HBV.Surface-enhanced laser desorption and ionization-time of flight-mass spectrometry(SELDI-TOF-MS)technique has been applied to gain the data of serum protein from two kinds of people and then PLS variable selection method has been used to establish the classification model.The cross validation relativities coefficients of the model came to 0.97.Furthermore the important factors or variables that discrim inateHBV patients and healthy people have been found by analyzing themodel.The variables are several peak intensities of prote in from som em / z sections, which can express the upregu lation or dow nregu lation of protein in the sections. As potential biomarkers, the proteinsmay be closely re lated to the causes o fHBV, wh ich can be deep ly studied. The classification f igures constructed by the fitting value of themodel in the article are clear and intuitive, and can express the discrim ination effect of the model in the art icle are clear and intu itive, and can express the discrim ination effect of the model well.本文系福建省自然科学基金(No. X0750052 )资助项

荒漠药用植物刺山柑产地适宜性数值分析/Suitability Evaluation of Capparis spinosa Based on TCMGIS[J]

目的:分析荒漠药用植物刺山柑产地适宜性.方法:应用"中药材产地适宜性分析地理信息系统(TCMGIS)",以新疆东部吐鲁番地区及新疆南部野牛刺山柑分布区的生态因子为依据,分析刺山柑在全国适宜产地.结果:新疆、内蒙古、甘肃、青海、宁夏5省区分布着刺山柑的适宜产区,共包括183个县市,总面积为1 251 361 km2.其中新疆北疆东部和新疆南部、内蒙占阿拉善高原、甘肃河西走廊北部、宁夏中北部是刺山柑适宜分布集中区.结论:刺山柑适宜区分析结果覆盖了第3次全国中药资源普查记载的全部区域,并且与历代本草记载的刺山柑产地及现代刺山柑引种的成功实践相吻合,对荒漠药材刺山柑的引种栽培及科学区划具有重要的参考价值