Objective:To investigate the influence of frailty on post-treatment outcomes in elderly heart failure patients with reduced ejection fraction treated with Sacubitril/Valsartan.Methods:The 231 heart failure patients aged 60 years or over with reduced ejection fraction were enrolled from October 2017 to October 2018 in Department of Geriatric Medicine, Henan Provincial People's Hospital.Patients were divided into the frailty group(n=116)and the control group(n=115). Frailty diagnosis was made by five indexes suggested by LP Fried.Both groups were treated with sacubitril/valsartan(49/51 mg)for 1 year.The left ventricular ejection(LVEF), estimated glomerular filtration rate(eGFR), N-terminal pro B-type natriuretic peptide(NT-proBNP)and other clinical and laboratory indexes were detected before and after treatment and compared between the frailty group and the control group.Results:16 subjects in the frailty group and 11 subjects in the control group dropped out of the study.The frailty group versus the control group showed a higher mortality rate of cardiovascular causes(13.0% or 13/100 vs.6.7% or 7/104, χ2=6.437, P=0.027), a higher first re-hospitalization rate(18.0% or 18/100 vs.11.5% or 12/104, χ2=4.458, P=0.043)and a higher all-cause mortality(16.0% or 16/100 vs.8.6% or 9/104, χ2=3.875, P=0.039). In the frailty group, levels of serum NT-proBNP and creatinine were higher and eGFR was lower after treatment than before treatment[(2 253±144) ng/L vs.(2 094±136) ng/L, (137±24) μmol/L vs.(125±23) μmol/L, (49.2±5.9) ml·min -1·1.73 m -2vs.(56.7±6.3) ml·min -1·1.73 m -2, t=3.674, 2.893 and 2.068, P=0.017, 0.026 and 0.029]. In the control group, serum NT-proBNP levels were lower after treatment than before treatment[(1 828±123) ng/L vs.(1 945±128) ng/L, t=1.896, P=0.043], while serum creatinine levels[(120±22) μmol/L vs.(117±19) μmol/L, t=2.099, P=0.650]and eGFR[(59.8±6.5) ml·min -1·1.73 m -2vs.(61.6±6.8) ml·min -1·1.73 m -2, t=2.444, P=0.173]had no significant difference between post-treatment and pre-treatment. Conclusions:Frailty has adverse affects on the mortality, re-hospitalization rate and renal function in elderly heart failure patients with reduced ejection fraction treated with Sacubitril/Valsartan.

Objective:To investigate the association of time in range(TIR) with the severity of coronary artery disease and acute coronary syndrome in patients with type 2 diabetes mellitus.Methods:A total of 216 patients with type 2 diabetes mellitus and coronary heart disease were recruited and undergone anthropometric and biochemical measurements, continuous glucose monitoring, and calculation of SYNTAX score. TIR was defined as the percentage of time within the glucose range of 3.9-10.0 mmol/L during 24 h. Spearman correlation analysis and multivariate linear regression analysis were used to evaluate the correlation factors of SYNTAX score. Multivariate logistic regression analysis was used to analyze the association of TIR with the severity of coronary artery disease and acute coronary syndrome. Results:Compared with patients with mild coronary artery disease, TIR in patients with moderate to severe coronary artery disease was lower[(69.4±17.3)% vs (60.8±17.8)%, t=3.0, P=0.003], and HbA 1C of patients with moderate to severe coronary artery disease was higher [(9.6±1.7)% vs (8.8±1.6)%, t=3.3, P=0.001]. SYNTAX score was negatively correlated with TIR ( r=-0.251, P<0.01) and positively correlated with HbA 1C ( r=0.249, P<0.01). Moreover, compared with HbA 1C (standardized coefficients=0.181, P=0.007), TIR (standardized coefficients=-0.192, P=0.004) had a greater influence on SYNTAX score. Multivariate linear regression analysis showed that TIR, HbA 1C, duration of diabetes and smoking were independently correlated with SYNTAX score. Multivariate logistic regression analysis revealed that compared with TIR Q1, Q3 and Q4 were independent protective factors for moderate to severe coronary artery disease (respectively, OR=0.61 and 0.59, 95% CI 0.39-0.96 and 0.38-0.94, P=0.014 and 0.009) and acute coronary syndrome (respectively, OR=0.51 and 0.39, 95% CI 0.32-0.95 and 0.26-0.75, P=0.022 and 0.008). Conclusion:TIR was significantly and independently correlated with the severity of coronary artery disease and acute coronary syndrome in type 2 diabetes mellitus after controlling confounding factors. When TIR level was decreased, the severity of coronary artery disease was aggravated, and SYNTAX score and the risk of acute coronary syndrome was increased.

Objective:To investigate the association of time in range with metabolic associated fatty liver disease(MAFLD) and advanced liver fibrosis in patients with type 2 diabetes.Methods:This study was a retrospective study. A total of 494 type 2 diabetic patients were recruited in the Department of Endocrinololgy of Henan Provincial People′s Hospital from November 2019 to April 2022. Time in range(TIR) was calculated with continuous glucose monitoring data. Abdominal ultrasound scan was used to diagnose fatty liver. Liver stiffness measurement(LSM) by transient elastography was used to evaluate liver fibrosis. Pearson and multivariate linear regression analysis was used to evaluate the association between TIR and LSM. Multivariate logistic regression analysis was used to analyze the association of TIR with risk of MAFLD and advanced liver fibrosis.Results:Pearson correlation analysis showed that LSM was negatively correlated with TIR( r=-0.86, P<0.001) and was positively correlated with homeostasis model assessment for insulin resistance(HOMA-IR; r=0.48, P<0.001). After adjusting for confounding factors, multivariate linear regression analysis showed that TIR significantly negatively predicted LSM( β=-0.75, P<0.001), and HOMA-IR significantly positively predicted LSM( β=0.21, P=0.025). After adjusting for confounding factors, logistic regression analysis showed that compared with TIR Q4 patients, TIR Q1 patients had an increased risk of MAFLD( OR=1.96, 95% CI 1.07-3.62, P=0.027), advanced liver fibrosis( OR=3.82, 95% CI 1.17-12.50, P=0.027), and HOMA-IR was an independent risk factor for MAFLD( OR=1.22, 95% CI 1.04-1.43, P=0.005) and advanced liver fibrosis( OR=1.26, 95% CI 1.03-1.54, P=0.025). Conclusions:TIR and insulin resistance are independent risk factors for MAFLD and advanced liver fibrosis in patients with type 2 diabetes. TIR has a significant predictive value for MAFLD and advanced liver fibrosis.

The recent advancement of single-cell RNA sequencing (scRNA-seq) technologies facilitates the study of cell lineages in developmental processes and cancer.In this study,we developed a computational method,called redPATH,to reconstruct the pseudo developmental time of cell lineages using a consensus asymmetric Hamiltonian path algorithm.Besides,we developed a novel approach to visualize the trajectory development and implemented visualization methods to provide biological insights.We validated the performance of redPATH by segmenting different stages of cell development on multiple neural stem cell and cancer datasets,as well as other single-cell transcriptome data.In particular,we identified a stem cell-like subpopulation in malig-nant glioma cells.These cells express known proliferative markers,such as GFAP,ATP1A2,IGFBPL1,and ALDOC,and remain silenced for quiescent markers such as ID3.Furthermore,we identified MCL1 as a significant gene that regulates cell apoptosis and CSF1R for reprogram-ming macrophages to control tumor growth.In conclusion,redPATH is a comprehensive tool for analyzing scRNA-seq datasets along the pseudo developmental time.redPATH is available at https://github.com/tinglabs/redPATH.