Objectives:To investigate the prognostic value of the CHA2DS2-VASc and R2CHA2DS2-VASc scores in patients with atrial fibrillation(AF)and heart failure(HF).Methods:Patients with AF and HF from hospitals diagnosed by the Heart Failure Center in Guangdong Province between January 2017 and December 2021 were selected.Major adverse cardiovascular events(MACE)were used as the follow-up endpoint.Statistical methods such as the area under the receiver operating characteristic(ROC)curve(AUC),net reclassification index(NRI),and integrated discrimination improvement(IDI)were applied to evaluate the predictive value of the CHA2DS2-VASc and R2CHA2DS2-VASc scores in patients with AF and HF.Results:A total of 1 839 patients were enrolled in this study,comprising 703 patients in the MACE group and 1 136 patients in the non-MACE group.Compared with the non-MACE group,the MACE group exhibited significantly advanced age,higher prevalence of New York Heart Association class Ⅳ and coronary artery disease,lower diastolic blood pressure and estimated glomerular filtration rate levels,and elevated serum N-terminal pro-B-type natriuretic peptide concentrations(all P<0.05).Additionally,significantly lower proportions of patients in the MACE group received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors,beta-blockers,mineralocorticoid receptor antagonists,or anticoagulant therapy(all P<0.05).Multivariable logistic regression analysis revealed that each 1-point increment in both CHA2DS2-VASc and R2CHA2DS2-VASc scores was associated with approximately 10%increased risk of MACE.ROC curve analysis demonstrated that the AUC values for predicting MACE in AF patients with HF were 0.555(95%CI:0.528-0.582,P<0.001)for CHA2DS2-VASc and 0.576(95%CI:0.549-0.608,P<0.001)for R2CHA2DS2-VASc,indicating marginally superior discriminatory capacity of the R2CHA2DS2-VASc score.Delong's test confirmed statistically significant differences between the two scoring systems(P=0.001).The R2CHA2DS2-VASc score demonstrated a NRI of 0.259(95%CI:0.166-0.352,P<0.001)and an IDI of 0.007(95%CI:0.005-0.010,P<0.001)compared with the conventional CHA2DS2-VASc score.Although the R2CHA2DS2-VASc score exhibited slightly better predictive accuracy and outcome discrimination capacity than the original scoring system,both scores demonstrated suboptimal clinical predictive performance.Conclusions:Both the R2CHA2DS2-VASc and CHA2DS2-VASc scores show suboptimal performance for predicting the risk of MACE in patients with AF and HF,and the predicting performance of R2CHA2DS2-VASc score is marginally superior to CHA2DS2-VASc score in this patient cohort.

Objectives:To investigate the prognostic value of the CHA2DS2-VASc and R2CHA2DS2-VASc scores in patients with atrial fibrillation(AF)and heart failure(HF).Methods:Patients with AF and HF from hospitals diagnosed by the Heart Failure Center in Guangdong Province between January 2017 and December 2021 were selected.Major adverse cardiovascular events(MACE)were used as the follow-up endpoint.Statistical methods such as the area under the receiver operating characteristic(ROC)curve(AUC),net reclassification index(NRI),and integrated discrimination improvement(IDI)were applied to evaluate the predictive value of the CHA2DS2-VASc and R2CHA2DS2-VASc scores in patients with AF and HF.Results:A total of 1 839 patients were enrolled in this study,comprising 703 patients in the MACE group and 1 136 patients in the non-MACE group.Compared with the non-MACE group,the MACE group exhibited significantly advanced age,higher prevalence of New York Heart Association class Ⅳ and coronary artery disease,lower diastolic blood pressure and estimated glomerular filtration rate levels,and elevated serum N-terminal pro-B-type natriuretic peptide concentrations(all P<0.05).Additionally,significantly lower proportions of patients in the MACE group received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors,beta-blockers,mineralocorticoid receptor antagonists,or anticoagulant therapy(all P<0.05).Multivariable logistic regression analysis revealed that each 1-point increment in both CHA2DS2-VASc and R2CHA2DS2-VASc scores was associated with approximately 10%increased risk of MACE.ROC curve analysis demonstrated that the AUC values for predicting MACE in AF patients with HF were 0.555(95%CI:0.528-0.582,P<0.001)for CHA2DS2-VASc and 0.576(95%CI:0.549-0.608,P<0.001)for R2CHA2DS2-VASc,indicating marginally superior discriminatory capacity of the R2CHA2DS2-VASc score.Delong's test confirmed statistically significant differences between the two scoring systems(P=0.001).The R2CHA2DS2-VASc score demonstrated a NRI of 0.259(95%CI:0.166-0.352,P<0.001)and an IDI of 0.007(95%CI:0.005-0.010,P<0.001)compared with the conventional CHA2DS2-VASc score.Although the R2CHA2DS2-VASc score exhibited slightly better predictive accuracy and outcome discrimination capacity than the original scoring system,both scores demonstrated suboptimal clinical predictive performance.Conclusions:Both the R2CHA2DS2-VASc and CHA2DS2-VASc scores show suboptimal performance for predicting the risk of MACE in patients with AF and HF,and the predicting performance of R2CHA2DS2-VASc score is marginally superior to CHA2DS2-VASc score in this patient cohort.

Objective:To explore the methods and ideas for developing pharmaceutical care in clinical practice. Methods: The pharmaceutical care performed by clinical pharmacists and the therapeutic scheme assisted by clinical pharmacists for one patient with adult purulent meningitis were analyzed retrospectively. Results and Conclusion:Through selection of anti-infective agents, treatment of adverse drug reactions and assessment of patients’ economic capacity,clinical pharmacists help provide reasonable medication to im-prove therapeutic efficacy, safety and economy.

Objective To detect the different expressions of Drosha between endometrial cancer (EC) tissue and other tissues and to explore correlation between Drosha mRNA transcription level and protein expression level with clinicopatho?logical characteristics of EC. Methods The mRNA transcription and protein expression levels of Drosha were examinaned by q-PCR and Western blot respectively in normal endometrial tissues (25 cases), atypical hyperplasia of endometrial tis?sues (20 cases) and endometrial cancer tissues (40 cases). Correlations between Drosha mRNA transcription and protein ex?pression with clinicopathological characteristics of EC were analyzed. Results The levels of Drosha mRNA and protein lev?els in EC were obviously lower than those in endometrial atypical hyperplasia and normal endometrium (P<0.05). But there is no significant difference of Drosha expression between endometrial atypical hyperplasia and normal endometrium tissues (P>0.05). The protein expression levels of Drosha were consistent with transcription of mRNA transcription levels. Drosha mRNA expression does not differ significantly with differentiation, histological type, myometrial invasion, lymphatic metasta?sis and FIGO stages of EC (P>0.05). Conclusion The expression levels of Drosha in EC tissues were down-regulated, therefore the reduction of Drosha may contributed to tumorigenesis of EC.

[Objective]This study was designed to investigate the effects of 5-aminoimidasole-4-carboxamide ribonucleoside (AICAR)on activity of transcription factor Forkhead O 3a(FOXO3a)and expression of ubiquitin ligase muscle atrophy F-box (MAFbx),and to explore the role of adenosine monophosphate-activated protein kinase(AMPK)on proteolysis pathways in eardiomyocytes.[Methods]The effect of AICAR on activation of AMPK was observed.Cultured neonatal rat cardiomyocytes was treated with AICAR in different concentration.Cultured cardiomyocytes were then divided into three groups:control group,AICAR group,AICAR+Compound C group.Effects of AMPK activation on phosphorylation of FOXO3a and expression of MAFbx in cardiomyocytes were detected using Western blot.[Results]①Compared with control group,activity of AMPK in cultured cardiomyocytes was increased after treatment with 0.25 mmol/L or 0.5 mmol/L AICAR for 6 h(P＜0.05),and the activity of AMPK was further enhanced after treatment with 1.0 mmol/L or 2.0 mmol/L AICAR for 6 h(P＜0.01).②Activation of AMPK by AICAR significantly increased the transcriptional activity of FOXO3a(P＜0.01),and enhanced MAFbx protein expression in cardiomyocytes when comparing with control group(P＜0.01),however,specific AMPK antagonist Compound C markedly reversed these effects induced by AICAR.[Conclusion]AMPK may regulate cardiomyocytes proteolysis by activation of FOXO3a transcription factor,and up-regulation of MAFbx protein expression.

AIM: To study the effects of metformin on the pressure overload-induced cardiac hypertrophy in rats. METHODS: Transverse aortic constriction (TAC) model of rat was made through laparotomy. One week after TAC surgery, the rats were randomly divided into 5 groups (n=8 in each group) and were administered with the corresponding drugs orally every day for 8 weeks: sham group (sham surgery, administered with 2 mL distilled water);TAC group (TAC rats, administered with 2 mL distilled water);metformin(MET) group (TAC rats, administered with MET at dose of 300 mg·kg~(-1)·d~(-1));MN group [TAC rats, administered with MET at dose of 300 mg·kg~(-1)·d~(-1) plus NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) 50 mg·kg~(-1)·d~(-1)] and L-NAME group (TAC rats, administered with L-NAME at dose of 50 mg·kg~(-1)·d~(-1)). After treated for 8 weeks, the echocardiography, hemodynamics, the ratio of heart weight to body weight (HW/BW) and histological examination of the heart were performed. The levels of myocardial AMP-activated protein kinase subunit α (AMPKα), p-AMPKα~(Thr172), endothelial nitric oxide synthase (eNOS) and p-eNOS~(Ser1177) were detected by Western blotting. Plasma and myocardial nitric oxide (NO) were detected biochemically. RESULTS: After 8 weeks treatment, the wall thickness of left ventricle, the heart weight/body weight ratio (HW/BW), and the left ventricular myocardial perivascular fibrosis and myocardial interstitial fibrosis of the animals in TAC group were significantly increased as compared to those in sham rats. Treatment with MET for 8 weeks significantly attenuated left ventricular hypertrophy and improved cardiac function in TAC rats. These effects of MET were mostly abolished by L-NAME. Molecular biology and biochemical testing revealed that the levels of left ventricular myocardial p-AMPKα~(Thr172) and p-eNOS~(Ser1177), as well as the levels of myocardial and serum NO were significantly increased in MET group. CONCLUSION: Long-term MET treatment significantly inhibits the cardiac hypertrophy and the myocardial fibrosis and improves the cardiac functions in pressure-overload rats. The anti-hypertrophic effects of MET may be mediated via activation of AMPK-eNOS signaling pathway.