| 3 | Association between single nucleotide polymorphisms in deoxycytidine kinase and treatment response among acute myeloid leukaemia patients显示文摘Development of resistance to 1-beta-arabinofuranosylcytosine (AraC) is a major obstacle in the treatment of patients with acute myeloid leukaemia (AML). Deficiency of functional deoxycytidine kinase (dCK) plays an important role in AraC resistance in vitro. We screened 5378 bp sequences of the dCK gene, including all exons and the 5' flanking region, and identified two single nucleotide polymorphisms (SNPs) in the regulatory region (rSNPs) with high allele frequencies. These two rSNPs (-201 C>T and -360C>G) formed two major haplotypes. Genotyping with sequencing and MassARRAY system among 122 AML patients showed that those with -360CG/-201CT and -360GG/-201TT compound genotypes (n = 41) displayed a favourable response to chemotherapy whereas those with -360CC/-201CC (n= 81) tended to have a poor response (P = 0.025). Moreover, real-time quantitative reverse transcriptase-polymerase chain reaction showed that patients with -360CG/-201CT and -360GG/-201TT genotypes expressed higher level of dCK mRNA compared to those with the -360CC/-201CC genotype (P = 0.0034). Luciferase-reporter assay showed that dCK 5' regulatory region bearing -360G/-201T genotype alone had an eight-fold greater transcriptional activation activity compared to that with -360C/-201C genotype, whereas co-transfection of both -360G/-201T and -360C/-201C constructs mimicked the heterozygous genotype, which exhibited a four-fold greater activity compared to that with -360C/-201C. These results indicate that rSNP haplotypes of dCK gene may serve as a genetic marker for predicting drug responsiveness, which will be beneficial in establishing more effective AML chemotherapeutic regimens. | JYShi ZZZhang SJZhu YMGu BWLi GBai XTGao XDHu JJin WHuang WChen ZChen | 2005 | 中国生物学文摘2005，19，6： | 0 |
| 4 | Outcomes of early hospital readmission after kidney transplantation: Perspectives from a Canadian transplant centre显示文摘BACKGROUND Early hospital readmissions(EHRs)after kidney transplantation range in incidence from 18%-47%and are important and substantial healthcare quality indicators.EHR can adversely impact clinical outcomes such as graft function and patient mortality as well as healthcare costs.EHRs have been extensively studied in American healthcare systems,but these associations have not been explored within a Canadian setting.Due to significant differences in the delivery of healthcare and patient outcomes,results from American studies cannot be readily applicable to Canadian populations.A better understanding of EHR can facilitate improved discharge planning and long-term outpatient management post kidney transplant.AIM To explore the burden of EHR on kidney transplant recipients(KTRs)and the Canadian healthcare system in a large transplant centre.METHODS This single centre cohort study included 1564 KTRs recruited from January 1,2009 to December 31,2017,with a 1-year follow-up.We defined EHR as hospitalizations within 30 d or 90 d of transplant discharge,excluding elective procedures.Multivariable Cox and linear regression models were used to examine EHR,late hospital readmissions(defined as hospitalizations within 31-365 d for 30-d EHR and within 91-365 d for 90-d EHR),and outcomes including graft function and patient mortality.RESULTS In this study,307(22.4%)and 394(29.6%)KTRs had 30-d and 90-d EHRs,respectively.Factors such as having previous cases of rejection,being transplanted in more recent years,having a longer duration of dialysis pretransplant,and having an expanded criteria donor were associated with EHR post-transplant.The cumulative probability of death censored graft failure,as well as total graft failure,was higher among the 90-d EHR group as compared to patients with no EHR.While multivariable models found no significant association between EHR and patient mortality,patients with EHR were at an increased risk of late hospital readmissions,poorer kidney function throughout the 1st year post-transplant,and higher hospital-based care costs within the 1st year of follow-up.CONCLUSION EHRs are associated with suboptimal outcomes after kidney transplant and increased financial burden on the healthcare system.The results warrant the need for effective strategies to reduce post-transplant EHR. | Olusegun Famure Esther DKim Yanhong Li Johnny WHuang Roman Zyla Magdalene Au Pei XuanChen Heebah Sultan Monika Ashwin Michelle Minkovich S Joseph Kim | 2023 | World Journal of Transplantation2023，13，6： | 0 |
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