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<p><b>OBJECTIVE</b>To investigate the variations of hepatitis C virus (HCV) quasispecies and the changes in their composition in untreated patients with chronic hepatitis C.</p><p><b>METHODS</b>Eleven patients chronic hepatitis C without previous specific anti-HCV treatment were tracked for disease progression and blood samples were collected at multiple time points. The major clinical parameters of liver function and viral load were tested. A fragment of HCV hypervariable region 1 (HVR1) was amplified and cloned, and the positive clones were sequenced and subsequently analyzed to determine the composition variation of HCV quasispecies during disease progression in relation to the major clinical parameters.</p><p><b>RESULTS</b>A total of 631 HVR1 sequences were acquired from the positive clones. The evolution of HCV HVR1 quasispecies in untreated chronic hepatitis C patients featured 3 patterns of variation in quasispecies composition, namely stable, fast and slow changes during the natural course of chronic hepatitis C. The genetic distance of the quasispecies was found to inversely correlated with ALT (R=-0.438, P=0.011) and AST level (R=-0.500, P=0.003), and sense mutation rate was also inversely correlated with ALT level (R=-0.387, P=0.026) and AST level (R=-0.410, P=0.018). No significant association was found between HCV load and any clinical or virological parameters.</p><p><b>CONCLUSION</b>Due to individual differences and immune pressure, HCV quasispecies can present with different patterns of evolution in the natural disease progression of chronic hepatitis C. HCV quasispecies evolution, due to its close correlation with the biochemical parameters, can be used to evaluate the severity and prognosis of chronic hepatitis C.</p>
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Humans , Base Sequence , Disease Progression , Genetic Variation , Hepacivirus , Genetics , Hepatitis C, Chronic , Virology , Viral LoadABSTRACT
Objective To study the whole-genome evolution of influenza B viruses prevalent in Qingdao from 2006 to 2011 .Methods RNA was extracted from influenza B viruses isolated in Qingdao from 2006 to 2011 .Each gene segment was amplified by reverse transcription polymerase chain reaction ( RT-PCR) and then sequenced .Gene sequences of each virus were determined and assembled by using Sequench -er software .A phylogenetic analysis for each gene segment was conducted by using MEGA 5.0 software pack-age.Results The phylogenetic tree of hemagglutinin ( HA) gene showed that 13 strains from 2006 to 2009 belonging to V1 clade of Victoria lineage were B/Malaysia/2506/2004-like viruses,and 12 strains from 2009 to 2011 belonging to the V2 clade of Victoria lineage were B/Brisbane/60/2008-like viruses.Moreover, strains of Yamagata lineage were all B/Florida/4/2006-like viruses including 5 strains of Y1 clade circulated from 2006 to 2008 and 7 strains of Y2 clade circulated from 2010 to 2011, respectively.The analysis of whole-genome evolution showed that 3 viruses of V2 clade presented 5+3 reassortment and 1 virus presented 1+7 reassortment.All reassortant strains matched with the vaccine strains of the present and previous season . The Yamagata and Victoria lineage strains belonged to genotype 2 and genotype 15,respectively.Compared with vaccine strains , the HA1 protein of Victoria lineage strains showed mutations at amino acid sites of H14Q, L58P, N129S, I146V, N171D and R279K, while R48K, K88R, P108A, N116K, S150I, N165Y, D196N,N202S and S229G amino acid mutations were mainly detected in Yamagata lineage strains .The sites 116 and 129,150,165,196 and 202 located in the 120,150,160 and 190 loops,respectively,which had been previously determined to be the hotspots under positive selection .Conclusion Both Yamagata and Victoria lineages of influenza B viruses were prevalent in Qingdao and evolved continuously from 2006 to 2011 .The selective pressure that a vaccine would provide was only to virus strains belonging to the same lineage ,sug-gesting a bivalent vaccine may be better for the induction of protective immunity .
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@#目的观察低分子量肝素治疗颈内动脉系统短暂性脑缺血发作(TIA)的疗效和安全性。方法选取颈内动脉系统TIA患者72例,随机分为治疗组和对照组各36例,均用低分子右旋糖酐静滴,治疗组加用低分子量肝素皮下注射。结果治疗组患者的疗效优于对照组(P<0.05),且无严重出血不良反应。结论低分子量肝素治疗颈内动脉系统TIA疗效佳,安全性高。