Objective To investigate the efficacy and safety of warfarin anticoagulation in Chinese elderly patients based on vitamin K epoxide reductase complex 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) genetic polymorphisms.Methods Clinical data of 41 elderly patients with initial anticoagulation therapy in our emergency department and respiratory department were collected.Patients were divided into observation group (n=20,patients treated with warfarin based on genetic polymorphisms) and control group (n =21,patients treated based on clinical experience).The international normalized ratio (INR),the time of INR stabilized within target range (2.0-3.0) and the incidence of bleeding episodes in 6-month follow up were compared between groups.Results INR within target range at day 3,4,5 and 7 were 0.0％,42.1％,52.6％,68.4％ in observation group and 0.0％,10.0％,25.0％,35.0％ in control group,respectively.There were significant differences in INR within target range at day 4,7 between the two groups (both P＜0.05),while no significant difference was found in INR within target range at day 5 (P＞0.05).The time of INR stabilized within target range was shorter in observation group than in control group [(9.5±2.4) d vs.(12.3± 4.8) d,P＜0.05].Bleeding complication occurred in 3 patients in observation group and 5 patients in control group,and there was no significant difference between the two groups.Conclusions Warfarin therapy based on VKORC1 and CYP2C9 gene polymorphisms may shorten the time of first INR reaching the target value and INR within target range in elderly patients.However,the risk of bleeding complications should be alerted.

Objective: To examine the association between sleep and frailty using the bidirectional two-sample Mendelian randomization (MR) approach, so as to provide the basis for the prevention and intervention of frailty. Methods: The data on single nucleotide polymorphisms (SNP) related to sleep duration, insomnia and morning chronotype were collected from genome-wide association studies (GWAS) and meta-analysis of GWAS, involving 446 118, 1 331 010 and 697 828 participants, respectively. The frailty was evaluated using the frailty index, and the relevant SNP data were collected from a meta-analysis of GWAS involving 175 226 participants. A bidirectional MR analysis was performed using the inverse-variance weighted method. Sensitivity analyses employed the weighted median method, the maximum likelihood-based method, the MR-Egger regression, and the MR-PRESSO test. Results: Forward MR analysis showed that longer sleep duration (β=-0.170, 95%CI: -0.255 to -0.085) and morning chronotype (β=-0.036, 95%CI: -0.058 to -0.014) decreased the risk of frailty, while insomnia increased the risk of frailty (β=0.167, 95%CI: 0.149-0.184). Reverse MR analysis showed that frailty increased the risk of insomnia (OR=1.645, 95%CI: 1.278-2.117). Both bidirectional MR results were robust, which excluded the impact of heterogeneity and horizontal pleiotropy. Conclusion Sleep duration, insomnia, and morning chronotype are associated with frailty.

Objective To assess the causality between 14 malignant tumors and hypertension.Methods Publicly available datasets from genome-wide association study were used,from which independent genetic variants strongly associated with hypertension and 14 malignant tumors were extracted as instrumental variables for bidirectional Mendelian randomization(MR)analysis,including random effect inverse variance weighted(IVW),simple mode,weighted median,weighted mode and MR-Egger to evaluate the causal effect.Sensitivity analysis was used to test the validity and robustness of the analytical results,and multivariate MR method was used to further control for the effects of confounding factors.Results In the MR analysis of malignant melanoma and hypertension,the study included a total of 11 single nucleotide polymorphisms(SNPs)strongly associated with malignant melanoma.After Bonferroni correction,the IVW-based results showed a causal relationship between malignant melanoma and hypertension(OR=1.67,95％CI:1.27-2.21,P＜0.001).Cochran's Q test,Mendelian randomization pleiotropy residual sum and outlier test and MR-Egger intercept test showed that there were no outliers and no horizontal pleiotropy among the instrumental variables,and the sensitivity analysis of the leave-one-out method showed that there was no single SNP that had a significant impact on the overall results.In the analysis of hypertension and leukemia,the preliminary analysis results showed that there may be a relationship between the two,but after adjusting for confounders,the effect of hypertension on the risk of leukemia was no longer significant.Conclusion Malignant melanoma may be a risk factor in the development of hypertension.