Objective:To investigate the use of non-vitamin K antagonist oral anticoagulants(NOACs)and their associated comorbidities in patients aged 80 years and older with non-valvular atrial fibrillation(NVAF), as well as to understand the challenges faced by elderly patients receiving NOAC therapy.Methods:We retrospectively enrolled elderly patients(≥80 years old)with NVAF who were treated with NOACs at a hospital in Beijing from January 2018 to August 2023.Patients were categorized into two age groups: 80-89 years and ≥90 years.We collected baseline data, including demographic characteristics, details of atrial fibrillation, comorbidities, laboratory test results, and medication combinations, for descriptive statistical analysis and intergroup comparisons.Results:A total of 695 elderly patients with NVAF receiving NOACs were included in the study, with a median age of 84 years.Among these patients, there were 328 males(47.19%, 328/695)and 422 cases of paroxysmal atrial fibrillation(60.72%, 422/695).The age group of 80-89 years comprised 640 cases(92.09%, 640/695), while the group aged 90 years and above included 55 cases(7.91%, 55/695).The use of NOACs in patients aged 90 and older exhibited an increasing trend over the years.Inter-group comparisons indicated that the ≥90 years group had lower body mass index, longer hospital stays, increased bedridden time, poorer renal function, lower levels of albumin and hemoglobin, and higher D-dimer levels.Inappropriate dosing of DOACs occurred in 49.64%(345/695)of cases, with 90.72%(313/345)receiving doses lower than recommended.Lower-than-recommended doses were more prevalent in the ≥90 years group, while higher-than-recommended doses were more common in the 80-89 years group.Polypharmacy was noted in 61.29%(426/695)of patients.The concurrent use of antiplatelet drugs, rhythm control medications, and ventricular rate control drugs was observed in 12.52%(87/695), 19.57%(136/695), and 54.53%(379/695)of patients, respectively, with no significant differences between groups.Conclusions:Inappropriate dosing and polypharmacy are prevalent issues among elderly NVAF patients.Therefore, it is essential to enhance multidisciplinary collaboration to optimize anticoagulation treatment strategies.

Angiogenesis within atherosclerotic plaques is a critical determinant of plaque stability.The biome-chanical microenvironment,consisting of fluid shear force,plaque structural stress,and matrix stiffness,serves as signifi-cant factors in mediating plaque angiogenesis.Endothelial cells respond to mechanical signals and participate in plaques neovascularization through force chemical signal transduction mechanisms.This review provides an overview of the mecha-nisms by which mechanical factors regulate angiogenesis within plaques and offers a novel therapeutic approach for the pre-vention and treatment of atherosclerosis.

Angiogenesis within atherosclerotic plaques is a critical determinant of plaque stability.The biome-chanical microenvironment,consisting of fluid shear force,plaque structural stress,and matrix stiffness,serves as signifi-cant factors in mediating plaque angiogenesis.Endothelial cells respond to mechanical signals and participate in plaques neovascularization through force chemical signal transduction mechanisms.This review provides an overview of the mecha-nisms by which mechanical factors regulate angiogenesis within plaques and offers a novel therapeutic approach for the pre-vention and treatment of atherosclerosis.

Objective:To investigate the use of non-vitamin K antagonist oral anticoagulants(NOACs)and their associated comorbidities in patients aged 80 years and older with non-valvular atrial fibrillation(NVAF), as well as to understand the challenges faced by elderly patients receiving NOAC therapy.Methods:We retrospectively enrolled elderly patients(≥80 years old)with NVAF who were treated with NOACs at a hospital in Beijing from January 2018 to August 2023.Patients were categorized into two age groups: 80-89 years and ≥90 years.We collected baseline data, including demographic characteristics, details of atrial fibrillation, comorbidities, laboratory test results, and medication combinations, for descriptive statistical analysis and intergroup comparisons.Results:A total of 695 elderly patients with NVAF receiving NOACs were included in the study, with a median age of 84 years.Among these patients, there were 328 males(47.19%, 328/695)and 422 cases of paroxysmal atrial fibrillation(60.72%, 422/695).The age group of 80-89 years comprised 640 cases(92.09%, 640/695), while the group aged 90 years and above included 55 cases(7.91%, 55/695).The use of NOACs in patients aged 90 and older exhibited an increasing trend over the years.Inter-group comparisons indicated that the ≥90 years group had lower body mass index, longer hospital stays, increased bedridden time, poorer renal function, lower levels of albumin and hemoglobin, and higher D-dimer levels.Inappropriate dosing of DOACs occurred in 49.64%(345/695)of cases, with 90.72%(313/345)receiving doses lower than recommended.Lower-than-recommended doses were more prevalent in the ≥90 years group, while higher-than-recommended doses were more common in the 80-89 years group.Polypharmacy was noted in 61.29%(426/695)of patients.The concurrent use of antiplatelet drugs, rhythm control medications, and ventricular rate control drugs was observed in 12.52%(87/695), 19.57%(136/695), and 54.53%(379/695)of patients, respectively, with no significant differences between groups.Conclusions:Inappropriate dosing and polypharmacy are prevalent issues among elderly NVAF patients.Therefore, it is essential to enhance multidisciplinary collaboration to optimize anticoagulation treatment strategies.

Objective:To assess the prognostic impact of frailty on elderly inpatients with heart failure.Methods:This prospective cohort study enrolled 121 in elderly patients with heart failure from Beijing Hospital, the General Hospital of the People's Liberation Army, and Beijing Tsinghua Changgung Hospital between September 2018 and April 2019.Patients were assessed for frailty using the Fried frailty phenotype and categorized into frail and non-frail groups.Follow-ups were conducted at 3-, 6-, and 12-months post-enrollment through clinic visits or phone calls to record adverse events.Composite endpoints include all-cause mortality and rehospitalization duo to deterioration of heart failure.Results:The study included 121 patients with an average age of 78.0±7.4 years, of whom 71(58.7%)were male and 57(47.1%)were classified as frail.Compared to the non-frail group, the frail group had lower estimated glomerular filtration rates[49.5±20.7 ml/(min·1.73m 2) vs.(64.0±27.1)ml/(min·1.73m 2)], lower scores in Basic Activities of Daily Living[5.0(4.0, 6.0) vs.6.0(5.0, 6.0)], Instrumental Activities of Daily Living[2.0(1.3, 7.8) vs.7.0(5.0, 8.0)], and Mini-Mental State Examination[26.0(16.0, 28.0) vs.27.0(22.3, 29.0)], all P<0.05.They also experienced longer hospital stays[10.5(6.0, 18.8)days vs.8.0(6.0, 11.8)days, P=0.008].During the follow-up period, the incidence of composite endpoint events was significantly higher in the frail group(43.9% vs.25.0%, P=0.029).Kaplan-Meier survival analysis demonstrated that the one-year incidence of composite endpoint events was significantly higher in the frail group( P=0.013).Multivariable Cox regression analysisindicated that frailty was an independent risk factor for composite endpoint events( HR=2.201, 95% CI: 1.089-4.447, P=0.028). Conclusions:Frailty is an independent risk factor for poor outcomes in elderly hospitalized patients with heart failure and should be considered a crucial factor in clinical assessment and treatment strategies.

Purpose To investigate whether ketogenic diet(KD)can promote cognition by regulating brain metabolism and neuroinflammation in Alzheimer's disease model mice.Materials and Methods Twenty male APP/PS1 mice were randomly assigned to either a KD group(APP/PS1+KD)or a regular diet group(APP/PS1),with 10 mice in each group.Additionally,10 wild-type C57BL/6 male mice served as the control group.The APP/PS1+KD group was fed with a ketogenic feed,the APP/PS1 group received a regular diet,and the control group was maintained on standard chow for a duration of 4 months.Blood ketone levels of mice were monitored after 4 weeks and 4 months of continuous feeding.Cognitive function was assessed via the morris water maze.18F-FDG and 18F-DPA-714 micro PET/CT were performed to evaluate the effects of KD on glucose metabolism and neuroinflammation across various brain regions in the Alzheimer's disease mice.Following PET/CT imaging,brain tissue samples were collected,and the hippocampal Cal region was selected for paraffin sectioning to detect the expression of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 through immunofluorescence analysis.Results In the Morris water maze in the fourth month,compared with the control group,the APP/PS1 group had a significantly longer escape latency on days 3-4(P＜0.05 or P＜0.01).Compared with the control group,the APP/PS1 group showed a significant decrease in relative 18F-FDG uptake in brain regions such as the striatum,hippocampus,dorsal thalamus,central gray matter,superior colliculus,olfactory bulb,and midbrain(P＜0.01,P＜0.05).Compared with the APP/PS1 group,the APP/PS1+KD group showed a significant increase in relative 18F-FDG uptake in the hippocampus and dorsal thalamus(P＜0.01).Compared with the control group,the APP/PS1 group showed a significant increase in relative uptake of 18F-DPA-714 in brain regions such as the striatum,hippocampus and hypothalamus(P＜0.05 or P＜0.001).Compared with the APP/PS1 group,the APP/PS1+KD group decreased the relative uptake of 18F-DPA-714 in the hippocampus(P＜0.01).Compared with the control group and APP/PS1+KD group,the fluorescence intensity of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 protein in the brain(hippocampus)of APP/PS1 group mice was significantly increased(both P＜0.01).Conclusion KD has the potential to ameliorate cognitive and behavioral deficits in APP/PS1 mice by enhancing brain metabolism and attenuating neuroinflammation.

Epilepsy is a common disease in nervous system, of which patients often present with spontaneous unpredictable spontaneous seizures. Sudden unexpected death in epilepsy (SUDEP) is one of the most serious complications of epilepsy, and it is also the main cause of premature death of epileptic patients. Generalized tonic-clonic seizures, age and genetic factors are common risk factors of SUDEP. This article summarizes the classification of SUDEP and epidemiology, mechanism, risk factors, risk assessment and preventive methods of SUDEP to help physicians to understand the difference between SUDEP and sudden cardiac death.

Objective:To investigate the safety and efficacy of individualized sunitinib schedule for patients with metastatic renal cell carcinoma (mRCC) according to the monitoring results of plasma drug concentration.Methods:The clinical data of patients with mRCC who received sunitinib treatment in our center from January 2014 to December 2020 were retrospectively analyzed, including 20 patients who underwent monitoring of plasma drug concentration (monitoring group), and 45 patients, matched by propensity score matching, received sunitinib but did not undergo monitoring of plasma drug concentration during the same period (unmonitored group). In the monitoring group, there were 12 males and 8 females. The mean age was 52.9 years, and ECOG score ≤1 in 16 cases (80%). Three patients were in the IMDC favorable-risk group, 15 patients were in the intermediate-risk group, and 2 patients were in the high-risk group. There were 18 cases of clear cell carcinoma and 2 cases of non-clear cell carcinoma, 5 cases of ISUP grade 1-2 and 11 cases of grade 3-4. In the unmonitored group, there were 31 males and 14 females. The mean age was 57.7 years, and 30 patients had ECOG score ≤1, 15 cases ≥2. There were 10 cases in IMDC favorable-risk group, 23 cases in intermediate-risk group, and 12 cases in high-risk group. Thirty-seven cases were clear cell carcinoma and 8 cases were non-clear cell carcinoma, 8 cases were in ISUP grade 1-2 and 28 cases in grade 3-4. There were no statistically significant differences between the two groups in the above parameters ( P>0.05). The monitoring group used the regimen of taking sunitinib for 4 weeks and stopping for 2 weeks (4/2 week) in the first cycle. The blood concentration of sunitinib was monitored before the first cycle and on days 4, 7, 10, 14, 21 and 28, and personalized medication plan was formulated according to the curve of the blood concentration. The 4/2 week scheme was adopted in the undetected monitoring group.The two groups were compared in the incidence of adverse events (AEs), progression-free survival (PFS), overall survival (OS), tumor treatment response and other clinical outcomes. Results:In the monitoring group, 90% (18/20) of patients receiving sunitinib had a steady-state plasma concentration of more than 150ng/ml, of which 10 patients (50%) had a plasma concentration of 150-200 ng/ml and 8 patients (40%) had a plasma concentration of more than 200 ng/ml. Meanwhile, all patients with plasma concentration higher than 150 ng/ml developed severe AEs (grade 3 and above) after treatment. The other two patients' plasma concentration were 100-150 ng/ml, and did not have severe AEs.All patients in the monitoring group received individualized medication schedule adjustment according to the plasma drug concentration and the occurrence point of severe AEs, ensuring that the peak plasma drug concentration was maintained at about 100-150 ng/ml. Among them, 6 patients were changed to take 2 weeks and stop for 1 week (2/1 week schedule), 4 patients were changed to take 10 days and stop for 5 days (10/5 d schedule), 7 patients were changed to take 7 days and stop for 3 days (7/3 d schedule), and 3 patients were changed to take 5 days and stop for 2 days (5/2 d schedule). The incidence of severe AEs significantly decreased from 90% (18/20) to 35% (7/20), and the difference was statistically significant ( P=0.003), while the incidence of grade 3 and higher AEs was 55.6% (25/45) in the standard group, which was statistically significant compared with the incidence of severe AEs before adjustment in the monitoring group ( P=0.006). Further analysis of the efficacy difference between the two groups showed that the overall objective response rate in the monitoring group (40%, 8/20) was higher than that in the standard group (20%, 9/45), although the difference was not statistically significant ( P=0.09). Median PFS and OS were significantly longer in the monitored group than in the standard group (PFS: 23 vs. 10 months, P=0.002; OS: not reached vs.25 months, P=0.005). Conclusions:The bioavailability of sunitinib is high in mRCC patients, which may lead to higher plasma drug concentration, adjustment of medication regimen based on blood concentration monitoring significantly improved patient safety and clinical outcomes. However, further validation by larger-scale, multi-center and prospective studies is needed.

Objective:To establish an outpatient operation simulation model by using pediatric outpatient data of a third-level maternal and child health hospital in Shenzhen, then to explore and improve hospital management problems.Methods:The hospital information system was used to extract the parameters of the pediatric outpatient data, and the AnyLogic simulation model was used to compare the hospital operation data and simulation data. Through the ideal operation status of the model and the actual state data of the hospital, the problems that were easily overlooked and difficult to investigate were identified. Then the problems were confirmed through on-site tracking investigations, improve process execution, and reduce waiting and congestion.Results:The gap between simulation data and hospital operation data was reflected in the waiting links of the first visit, inspection project and report interpretation. The process transformation of these three links could be the key to improving the overall service capability.Conclusions:Simulation and field tracking are effective ways to explore process problems. The method that simulation model is used to realize the method path of "big data→simulation→site tracking→management analysis improvement" , is suitable for the application and research of hospital process problem discovery.