OBJECTIVES: To create a mixed valvular heart disease (MVHD)-related age-adjusted comorbidity index (MVACI) model for predicting mortality risk of patients with MVHD. METHODS: A total of 4080 patients with moderate or severe MVHD in the China-VHD study were included. The primary endpoint was 2-year all-cause mortality. A MVACI model prediction model was constructed based on the mortality risk factors identified by univariate and multivariate Cox regression analysis. Restricted cubic splines were used to assess the relationship between MVACI scores and 2-year all-cause mortality. The optimal threshold, determined by the maximum Youden index from receiver operator characteristic (ROC) curve analysis, was used to stratify patients. Kaplan-Meier method was used to calculate 2-year all-cause mortality and compared using the Log-rank test. Univariate and multivariate Cox proportional hazards models were employed to calculate hazard ratios (HR) and 95% confidence intervals (CI), evaluating the association between MVACI scores and mortality. Paired ROC curves were used to compare the discriminative ability of MVACI scores with the European System for Cardiac Operative Risk Evaluation Ⅱ(EuroSCORE Ⅱ) or the age-adjusted Charlson comorbidity index (ACCI) in predicting 2-year clinical outcomes, while calibration curves assessed the calibration of these models. Internal validation was performed using the Bootstrap method. Subgroup analyses were conducted based on etiology, treatment strategies, and disease severity. RESULTS: Multivariate analysis identified the following variables independently associated with 2-year all-cause mortality in patients: pulmonary hypertension, myocardiopathy, heart failure, low body weight (body mass index <18.5 kg/m²), anaemia, hypoalbuminemia, renal insufficiency, cancer, New York Heart Association (NYHA) class and age. The score was independently associated with the risk of all-cause mortality, and exhibited good discrimination (AUC=0.777, 95%CI: 0.755-0.799) and calibration (Brier score 0.062), with significantly better predictive performance than EuroSCORE Ⅱ or ACCI (both adjusted P<0.01). The internal validation showed that the MVACI model's predicted probability of 2-year all-cause mortality was generally consistent with the actual probability. The AUCs for predicting all-cause mortality risk were all above 0.750, and those for predicting adverse events were all above 0.630. The prognostic value of the score remained consistent in patients regardless of their etiology, therapeutic option, and disease severity. CONCLUSIONS The MVACI was constructed in this study based on age and comorbidities, and can be used for mortality risk prediction and risk stratification of MVHD patients. It is a simple algorithmic index and easy to use.
Humans ; Prognosis ; Comorbidity ; Heart Valve Diseases/epidemiology* ; Female ; Male ; Middle Aged ; Aged ; Proportional Hazards Models ; Risk Factors ; China/epidemiology* ; Age Factors ; Risk Assessment ; Adult ; ROC Curve

Objective: To explore the effect of dapagliflozin(DAPA) on the function of rat endothelial progenitor cells(EPCs) culturedin vitroin a high glucose environment. Methods: Bone marrow derived EPCs from sprague-dawley(SD) rats were identified by fluorescence staining. EPCs were divided into control group(CG group), high glucose group(HG group), high glucose + DAPA group(GD group) and high glucose + DAPA + LY294002 group(GDL group). MTT assay, flow cytometry, tubule formation assay were used to detect the viability, apoptosis, tubule formation ability of EPCs, respectively. Western blot was used to detect the protein expression of AKT/eNOS signaling pathway. Results: Compared with CG group, cell viability, the ability to form tubules, the protein expression of p-AKT and p-eNOS, and the ratio of p-AKT/AKT and p-eNOS/eNOS in HG group significantly decreased(P<0.05), while the apoptosis rate of EPCs significantly increased(P<0.05). Compared with HG group, cell viability, the ability to form tubules, the protein expression of p-AKT and p-eNOS, and the ratio of p-AKT/AKT and p-eNOS/eNOS in GD group significantly increased(P<0.05), while the apoptosis rate of EPCs was significantly reduced(P<0.05). Compared with GD group, cell viability, the ability to form tubules, the protein expression of p-AKT and p-eNOS, and the ratio of p-AKT/AKT and p-eNOS/eNOS in GDL group significantly decreased(P<0.05), while the apoptosis rate of EPCs significantly increased(P<0.05). Conclusion DAPA can protect EPCs from high glucose induced functional damage through AKT/eNOS pathway.

OBJECTIVETo investigate the clinical characteristics and GCH I gene mutations in patients with dopa-responsive dystonia (DRD).

METHODSThe clinical features of 3 families with 6 affected members and 8 sporadic cases were analyzed to determine the clinical characteristics, and 2 families with 4 affected members and 2 sporadic cases were screened for mutations of the GCH I gene.

RESULTSAge at onset was (10 +/- 3) years. Onset occurred earlier in female (9 +/- 4) years than in male (12 +/- 1) years. The initial symptom was a gait disorder, dystonia or tremor in most patients and nine patients (64%) presented with diurnal fluctuation. Thirteen patients (93%) were cured and one was improved after administration of low doses of levodopa for 3 months and no long-term side effects of levodopa had occurred. Two independent mutations were found in three patients. Gln161Pro, a new missense mutation, was found in a sporadic case, leading to a relatively severe phenotype. The two patients with mild phenotype in one family were found to have Lys224Arg mutation, as previously described.

CONCLUSIONSDRD patients have diverse phenotypes and diurnal fluctuation is an important feature. They have dramatic and sustained response to levodopa. There may be a correlation between genotype and phenotype. The detection of GCH I mutations is helpful in early diagnosis of non-typical cases.

Age of Onset ; Child ; China ; DNA Mutational Analysis ; Dopamine Agents ; therapeutic use ; Dystonia ; diagnosis ; drug therapy ; genetics ; physiopathology ; Early Diagnosis ; Female ; GTP Cyclohydrolase ; genetics ; Genotype ; Humans ; Levodopa ; therapeutic use ; Male ; Molecular Sequence Data ; Mutation ; Mutation, Missense ; Pedigree ; Phenotype ; Polymerase Chain Reaction ; Sex Factors ; Treatment Outcome