目的 探讨谷氨酰转肽酶1(GGT1)基因单核苷酸多态性(SNP)对乳腺癌术后表柔比星联合环磷酰胺序贯紫杉醇类制剂(EC-T)化学药物治疗(简称化疗)方案血液系统毒性的影响.方法 收集徐州市妇幼保健院乳腺外科2021年1月至12月接受EC-T化疗方案的乳腺癌术后患者60例,采集患者的人口学资料和临床资料,并根据世界卫生组织(WHO)抗癌药物毒性分级标准对血液毒性分级.采用基因测序方法检测患者GGT1基因SNP位点的基因型,以Logistic回归模型评价各基因型与血液毒性发生的相关性.结果 rs5751901 位点共检出 TT 型(43.33％)、TC 型(38.33％)、CC 型(18.33％)3 种基因型,rs2017869 位点共检出 GG 型(41.67％)、GC型(40.00％)、CC型(18.33％)3种基因型.对于rs5751901位点,与TT型+TC型患者比较,CC型患者出现2级及以上中性粒细胞减少和白细胞减少的风险显著降低,与TT型+CC型患者比较,TC型患者出现2级及以上中性粒细胞减少的风险显著升高(P＜0.05).对于rs2017869位点,与GG型和GG型+GC型患者比较,CC型患者出现2级及以上血红蛋白减少的风险显著降低(P＜0.05).结论 rs5751901及rs2017869位点的CC基因型是乳腺癌术后患者接受EC-T化疗方案血液毒性减少的重要因素.

精益化管理这一新兴管理模式最先被应用在企业管理当中,鉴于其优越性,逐渐被引进运用于医院药事管理领域.相关研究发现,在医院药事管理中应用精益化管理模式,具有减少用药差错、提高患者满意度等优势,临床效果优于常规管理.妇幼专科医院具有其特殊性,用药安全尤为重要,笔者梳理了门急诊药房精益化管理的五项措施,旨在为妇幼专科门急诊药房精益化管理模式的构建提供参考.

目的 探讨X线修复交错互补基因1 (XRCC1) rs25487基因多态性对接受铂类药物联合方案化疗的非小细胞肺癌(NSCLC)患者预后的影响.方法 回顾性分析2014年1月至2018年9月在徐州医科大学附属医院行含铂类联合化疗方案治疗的NSCLC患者248例,收集患者的临床基本信息.采用PCR-RFLP法进行基因分型,分析XRCC1 rs25487的基因型和等位基因分布差异,观察各基因型对铂类药物的疗效差异.采用Log-Rank检验、Kaplan-Meier生存曲线和Cox风险回归模型评估各基因型患者间的预后差异.结果 与GG型患者相比,AG和AA型患者近期疗效改善明显(P=O.041),但远期疗效无显著差异(P＞0.05).与携带等位基因G患者相比,携带等位基因A患者中位无进展生存期和中位总生存期显著缩短(均P=0.019);携带等位基因A患者疾病进展风险增加(HR=1.567,95％CI:1.070～2.294,P=0.021),死亡风险增加(HR=1.572,95％CI:1.067～2.317,P=0.022).结论 XRCC1 rs25487位点多态性是江苏苏北地区汉族NSCLC患者预后不佳的重要因素,等位基因A是引起预后不佳的风险因子.

AIM To explore the correlation between genetic variants of isocitrate dehydrogenase 2 (IDH2) and ten-eleven-translocation protein 2 (TET2) and cytarabine sensitivity in European (CEU) and African (YRI) populations in order to promote personalized medicine.METHODS Cell lines derived from persons of CEU ancestry or YRI ancestry from international HapMap project were cultured,and then exposed to cytarabine in different concentration (1,5,40,80 μ mol ·L-1) for 72 h.Percent cell survival values and cytarabine sensitivity depicted by the lower area under the survival curve (AUC) were determined by Alamar Blue assay.The AUC of cytarabine was calculated using the trapezoidal rule.Genotyping of IDH2 and TET2 was conducted by Taqman PCR assay.RESULTS Within CEU population samples,the AUC of cytarabine in IDH2 rs2970356 mutant CG/GG genotype carriers and rs2970358 mutant AG/GG genotype carriers were significantly lower than that in IDH2 rs2970356 CC genotype carriers and rs2970358 AA genotype carriers (rs2970356:CG/GG vs.CC,P ＜ 0.05;rs2970358:AG/GG vs.AA,P ＜ 0.05).There was no SNP in TET2 in CEU population associated with cytarabine sensitivity depicted by lower AUC.Within YRI population samples,the AUC of cytarabine in IDH2 rs2970356 mutant CC/CG genotype carriers,and in TET2 rs2454206 and rs11248047 mutant AG/GG genotype carriers were significantly lower than that in IDH2 rs2970356 GG genotype carriers,TET2 rs2454206 and rs11248047 AA genotype carriers (rs2970356:CG/GG vs.CC,P ＜ 0.05;rs2454206:AG/GG vs.AA,P ＜ 0.05;rs11248047:AG/GG vs.AA,P ＜ 0.05).CONCLUSION The cytarabine sensitivity might be influenced by gene polymorphism of IDH2 and TET2 in YRI populations,and only by gene polymorphism of IDH2 in CEU populations.

OBJECTIVE:To investigate the correlation of XRCC1 rs25487 polymorphism with the occurrence of lung cancer. METHODS:A total of 208 patients with primary lung cancer of Han nationality in Northern Jiangsu selected from the Affiliated Hospital of Xuzhou Medical University during Sept. 2015-Jul. 2016 were included in lung cancer group. A total of 214 healthy volunteers of the hospital underwent physical examination were included in control group. PCR-RFLP was used to detect the genotypes at XRCC1 rs25487 locus,and Logistic regression model was used to evaluate the correlation of genotypes with the occurrence of lung cancer. RESULTS:There was no statistical significance in the distribution of age and gender between 2 groups (P＞0.05). The proportion of smoker in lung cancer group was significantly higher than control group,with statistical significance(P＜0.05). AA,AG and GG genotypes were detected at rs25487 locus of XRCC1 gene. The frequency of AA,AG and GG genotype were 43.5%,41.1%and 15.4% in control group and 28.8%,48.6% and 22.6% in lung cancer group,respectively. The frequencies of genotypes in 2 groups were in line with Hardy-Weinberg equilibrium(P＞0.05),but there was statistical significance in genotype distribution between 2 groups(P＜0.05). Compared with AA genotype,the risk of lung cancer in individuals carrying AG genotype increased by 2.265 fold [OR＝2.265,95%CI(1.299,3.950),P＝0.040;after corrected with gender,age and smoking history OR＝2.309,95%CI(1.274, 4.185),P＝0.006],with statistical significance. The risk of lung cancer in individuals carrying GG genotype increased by 1.310 fold [OR＝1.310,95%CI(0.771,2.228),P＝0.318;after corrected OR＝1.429,95%CI(0.811,2.518),P＝0.217],without statistical significance. CONCLUSIONS:rs25487 locus mutant heterozy-gosity of XRCC1 gene is risk factor of lung cancer in Han nationality from Northern Jiangsu,and smoking can increase the risk of lung cancer.

We have found that Fas/FasL-mediated “extrinsic” pathway promoted cell apoptosis induced by renal ischemic injury. This study is to elucidate the upstream mechanism regulating FasL-induced extrinsic pathway during renal ischemia/reperfusion. Results demonstrated that when SIRT2 was activated by renal ischemia/reperfusion, activated SIRT2 could bind to and deacetylate FOXO3a, promoting FOXO3a nuclear translocation which resulted in an increase of nuclear FOXO3a along with FasL expression and activation of caspase8 and caspase3, triggering cell apoptosis during renal ischemia/reperfusion. The administration of SIRT2 inhibitor AGK2 prior to renal ischemia decreased significantly the number of apoptotic renal tubular cells and alleviated ultrastructure injury. These results indicate that inhibition of FOXO3a deacetylation might be a promising therapeutic approach for renal ischemia /reperfusion injury.

目的 探讨重症感染儿童患者万古霉素血药浓度与肾损伤的关系,为减少药物不良反应、促进临床合理用药提供参考.方法 采用回顾性分析方法,收集我院2010年5月-2015年5月101例重症感染患儿病历信息和万古霉素血药浓度数据,分析万古霉素血药浓度变化与肌酐和尿素氮、胱抑素C、清除率的关系.结果 万古霉素血药浓度＞ 20 μg·mL-1患儿的治愈率与血药浓度＜ 10 μg·mL-1的患儿相比有增高趋势(94％ vs.85％,P=0.052).其中,22例重症感染患儿在万古霉素治疗前后血肌酐和尿素氮水平均在正常范围内,但胱抑素C水平[(1.76±0.33) mg·L-1]明显高于正常范围(0.51 ～ 1.09 mg· L-1).重症感染的新生患儿(年龄＜28d)万古霉素的清除率明显低于非新生患儿[(2.94±3.70) vs.(4.09±3.58) mL·mim-1·kg-1,P＜ 0.05].但不同性别儿童患者的清除率无显著差异(P＞0.05).结论 常规监测重症感染患儿万古霉素血药浓度和肾功能,给药个体化,能减轻早期肾损伤.