背景与目的：有研究表明，尿中修饰核苷的含量在多数恶性肿瘤患者中有明显升高。本研究拟探讨检测尿中核苷在胃癌诊断中的意义。方法：应用高效液相色谱法分别检测50名正常人与48例胃癌患者尿中15种核苷的水平，48例胃癌患者中有25例同时接受了血清CEA检测。结果：50名正常人和48例胃癌患者尿中15种核苷的平均值分别依次为：Pseu 22.91±4.90，34.87±21.41；00.34±0.32，0.62±0.82；AO.58±0.16，0.96+0.75；C0.17±0.15，0.24±0.19：m 500.03±0.07，0.07±0.06：10.26±0.10，0.43±0.36；mlll.34±0.34，2.44±1.39；ac4CO.75±0.24，1.08±0.72；GO.09±0.04，0.14±0.10；X1.20±0.42，1.90±1.09：m2G0。61±0.16，1.00±0。69；m6A0。04±1.13，0.07±0.08：mIA2.26±0.56，3.71±2.21：m22C1.34±0.27，2.25±1.39；mIG0。80±0。25，1。41±0.86。癌患者尿中除m5U外，其余14种核苷的平均值明显高于正常人（P<0.05）；次黄嘌呤与肿瘤大小，淋巴结转移正相关（P<0.05）；黄嘌呤核苷与肿瘤淋巴结转移正相关（JD<0.05）。以其中15种核苷浓度作为数据矢量，结合主成分分析。投影判别法区分正常人和胃癌患者，63%的胃癌患者被识别。识别率大大高于CEA检测（12%）。结论：胃癌患者尿中修饰核苷水平升高，检测尿中修饰核苷对胃癌的初筛有。定的参考意义。

为研究四环素调控的胰岛素表达载体肌肉直接注射后对实验性糖尿病小鼠的降糖作用，构建了质粒prTA-tet42rhINS。以链脲佐菌素（STZ）诱导Balb/C小鼠成糖尿病模型，300μg质粒注射至小鼠的股部肌肉，并同时在饮水中加入不同浓度强力霉素（Dox），监测小鼠末梢血糖、体重，测定血清人胰岛素、C肽水平。用RT2PCR检测小鼠肌肉注射部位组织中人胰岛素原mRNA水平的表达情况。结果表明：质粒prTA2tet42rhINS注射后，给予Dox可显著降低糖尿病小鼠的血糖，血清人胰岛素、C肽水平相应升高，体重增加。效果持续大约二周。小鼠肌肉组织中有人胰岛素原mRNA表达。降糖效果和基因表达程度随Dox浓度增加而增强。质粒prTA2tet42rhINS对STZ诱导的糖尿病小鼠高血糖起到明显的降低作用。在糖尿病小鼠肌肉组织能很好地表达，并受Dox调控。

对单核苷酸多态性（SNP）的概念及特性作了简要说明，介绍了14种检测SNP的方法，讨论了各种方法的原理及优缺点，并对目前SNP在遗传图的绘制、遗传病致病基因的搜寻、药物设计及法医学等方面的应用及其研究进展进行了综述。引用文献29篇。

Accurate and fast genotyping of single nucleotide polymorphisms(SNPs)is important in the human genome project. Here an automated fluorescent method that can rapidly and accurately genotype multiplex known SNPs was developed by using a homemade kit, which has lower cost but higher resolution than commercial kit. With this method, oncogene K-ras was investigated, four known SNPs of K-ras gene exon 1 in 31 coloerctal cancer patients were detected. Results indicate that mutations were present in 8(26%)of 31 patients, and most mutations were localized in codon 12. The presence of these mutations is thought to be a critical step and plays an important role in human colorectal carcinogenesisas

Colorectal cancer(CRC)is one of the most common malignancies worldwide.The incidence of CRC in the Chinese population has increased dramatically during the last two decades; however,nonrandom chromosomal alterations in Chinese patients have not been described.In the present study, comparative genomic hybridization(CGH)was applied to detect recurrent chromosome alterations in 26 primary colorectal carcinomas and 21 colorectal adenomas from Chinese patients.In CRC,several recurrent chromosomal changes were found,including gains of 8q (14/26 cases, 54%), 20q (54%), 3q (50%), 13q( 50%), 5p (46%), 7p (42%), 7q (42%), and 12p (38%) and losses of 18q (65%) and 17p (42%). From comparison with previous CGH studies,the frequent gains of 3q and 12p might be distinctive occurrences in Chinese patients.The distribution of frequently found chromosomal alterations in different locations was studied.The gain of 20q was more frequently found in colon cancer (P<0.01) and the gain of 12p was more frequently found in rectal cancer.Chromosomal alterations were found in 19/21 of adenomas; the most frequent chromosomal alteration was the loss of 18q (9/21 cases, 43%). These recurrent alterations provide several starting points for the isolation of candidate oncogenes and tumor suppressor genes.