目的:探讨胆汁酸谱在诊断妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)和无症状高胆汁酸血症(asymptomatic hypercholanemia of pregnancy,AHP)中的价值。方法:选取正常妊娠者100例、ICP患者60例、AHP患者30例,采...目的:探讨胆汁酸谱在诊断妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)和无症状高胆汁酸血症(asymptomatic hypercholanemia of pregnancy,AHP)中的价值。方法:选取正常妊娠者100例、ICP患者60例、AHP患者30例,采用高效液相色谱串联质谱(high performance liquid chromatography tandem mass spectrometry,HPLC-MS/MS)分析各组胆汁酸含量,并通过建立正交偏最小二乘判别分析(orthogonal projections to latent structures,OPLS-DA)模型,寻找ICP组和AHP组差异性的胆汁酸。利用受试者工作特征(receiver operating characteristic,ROC)曲线分析两者差异性胆汁酸以及联合指标的诊断效能。结果:15种胆汁酸中,除鹅脱氧胆酸(chenodeoxycholic acid,CDCA)外,其余胆汁酸的含量在3组间差异均有统计学意义(P<0.05);通过OPLS-DA模型找到ICP组和AHP组差异性的胆汁酸为牛磺结合型胆酸(taurocholic acid,TCA)、牛磺结合型鹅脱氧胆酸(taurochenodeoxycholic acid,TCDCA)、甘氨结合型胆酸(glycocholic acid,GCA)、甘氨结合型鹅脱氧胆酸(glycohenodeoxycholic acid,GCDCA)、牛磺结合型熊脱氧胆酸(tauroursodeoxycholic acid,TUDCA)。ROC结果显示,TCA的诊断效能最高,曲线下面积(area under curve,AUC)为0.808,联合TCA、TCDCA、GCA、GCDCA、TUDCA诊断ICP的效能更高,AUC为0.967,灵敏度为90.6%,特异度为98.0%。结论:ICP和AHP的胆汁酸谱有差异,利用OPLS-DA模型找到的差异性胆汁酸可以作为两者鉴别诊断的一种重要方法。展开更多
The MutS protein plays an important role in the DNA mismatch repair system. Mutations in the mutS gene can lead to genome instability and ultimately cell malfunction. Here we have established a method for identifying ...The MutS protein plays an important role in the DNA mismatch repair system. Mutations in the mutS gene can lead to genome instability and ultimately cell malfunction. Here we have established a method for identifying functional defective mutants of MutS by random mutation and rifampicin screening. Some novel functional sites in MutS were identified. The MutS mutant strains were analyzed using surface plasmon resonance, gel filtration and far-western methods to determine the molecular mechanisms behind the DNA mismatch repair function of MutS.展开更多
文摘目的:探讨胆汁酸谱在诊断妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)和无症状高胆汁酸血症(asymptomatic hypercholanemia of pregnancy,AHP)中的价值。方法:选取正常妊娠者100例、ICP患者60例、AHP患者30例,采用高效液相色谱串联质谱(high performance liquid chromatography tandem mass spectrometry,HPLC-MS/MS)分析各组胆汁酸含量,并通过建立正交偏最小二乘判别分析(orthogonal projections to latent structures,OPLS-DA)模型,寻找ICP组和AHP组差异性的胆汁酸。利用受试者工作特征(receiver operating characteristic,ROC)曲线分析两者差异性胆汁酸以及联合指标的诊断效能。结果:15种胆汁酸中,除鹅脱氧胆酸(chenodeoxycholic acid,CDCA)外,其余胆汁酸的含量在3组间差异均有统计学意义(P<0.05);通过OPLS-DA模型找到ICP组和AHP组差异性的胆汁酸为牛磺结合型胆酸(taurocholic acid,TCA)、牛磺结合型鹅脱氧胆酸(taurochenodeoxycholic acid,TCDCA)、甘氨结合型胆酸(glycocholic acid,GCA)、甘氨结合型鹅脱氧胆酸(glycohenodeoxycholic acid,GCDCA)、牛磺结合型熊脱氧胆酸(tauroursodeoxycholic acid,TUDCA)。ROC结果显示,TCA的诊断效能最高,曲线下面积(area under curve,AUC)为0.808,联合TCA、TCDCA、GCA、GCDCA、TUDCA诊断ICP的效能更高,AUC为0.967,灵敏度为90.6%,特异度为98.0%。结论:ICP和AHP的胆汁酸谱有差异,利用OPLS-DA模型找到的差异性胆汁酸可以作为两者鉴别诊断的一种重要方法。
基金supported by the National Natural Science Foundation of China (Grant No. 30670443)the Chinese Academy of Sciences (Grant Nos. KSCX1-YW-R-63, KSCX2-YW-G-017 and KZCX2-YW-420)
文摘The MutS protein plays an important role in the DNA mismatch repair system. Mutations in the mutS gene can lead to genome instability and ultimately cell malfunction. Here we have established a method for identifying functional defective mutants of MutS by random mutation and rifampicin screening. Some novel functional sites in MutS were identified. The MutS mutant strains were analyzed using surface plasmon resonance, gel filtration and far-western methods to determine the molecular mechanisms behind the DNA mismatch repair function of MutS.