MTCH2 stimulates cellular proliferation and cycles via PI3K/Akt pathway in breast cancer.

The MTCH2 protein is located on the mitochondrial outer membrane and regulates mitochondria-related cell death. This study set out to investigate the role of MTCH2 in the underlying pathophysiological mechanisms of breast cancer (BC). MTCH2 expression levels in BC were analyzed using bioinformatics prior to verification by cell lines in vitro. Experiments of over-expression and siRNA-mediated knockdown of MTCH2 were conducted to assess its biological functions, including its effects on cellular proliferation and cycle progression. Xenografts were utilised for in vivo study and signaling pathway alterations were examined to identify the mechanisms driven by MTCH2 in BC proliferation and cell-cycle regulation. MTCH2 was up-regulated in BC and correlated with patients' overall survival. Over-expression of MTCH2 promoted cellular proliferation and cycle progression, while silencing MTCH2 had the opposite effect. Xenograft experiments were utilised to confirm the in vitro cellular findings and it was identified that the PI3K/Akt signaling pathway was activated by MTCH2 over-expression and suppressed by its silencing. Moreover, the activation of IGF-1R rescued cellular growth and cycle arrest induced by MTCH2-silencing. Overall, this study reveals that expression of MTCH2 in BC is upregulated and potentiates cellular proliferation and cycle progression via the PI3K/Akt pathway.

A prediction model based on functional mitral regurgitation for the recurrence of paroxysmal atrial fibrillation (PAF) after post-circular pulmonary vein radiofrequency ablation (CPVA).

AIM: To construct a prediction model based on functional mitral regurgitation (FMR) in patients with paroxysmal atrial fibrillation (PAF) to predict atrial fibrillation recurrence after the post-circular pulmonary vein radiofrequency ablation (CPVA). METHODS: We retrospectively analyzed 289 patients with PAF who underwent CPVA for the first time. The patients were randomly divided into modeling group and verification group at the ratio of 75:25. In the modeling group, the multivariate logistic regression was used to analyze and construct a prediction model for post-CPVA recurrence in PAF patients, which was then validated in the verification group. RESULTS: (1) After 3-6 months of follow-up, the patients were divided into sinus rhythm group (252 cases) and recurrence group (24 cases); (2) In the modeling group, the age, left atrial diameter (LAD), and the degree of MR (mild, moderate, severe) were higher in recurrence group than that of the sinus rhythm group, and the left atrial appendage emptying velocity (LAAV) was lower in recurrence group (all p < .05). (3) A model for predicting the recurrence of PAF after radiofrequency ablation was constructed in the modeling group. The equation was: Logit(P) = -3.253 + .092 × age + 1.263 × mild MR + 2.325 × moderate MR + 5.111 × severe MR -.113 × LAAV. The area under the curve (AUC) of the model was .889 in modeling group and .866 in verification group, and the difference was not statistically significant (p > .05). CONCLUSION: The prediction model of atrial fibrillation (AF) recurrence after CPVA in PAF patients has good predictive efficacy, specificity, and accuracy.

Investigating the association between P wave duration and atrial fibrillation recurrence after radiofrequency ablation in early persistent atrial fibrillation patients.

BACKGROUND: In the present study, we aimed to explore the association between P wave duration, as the measured time from the start point of the P wave to the end point, and atrial fibrillation recurrence after transcatheter radiofrequency ablation in patients with early persistent atrial fibrillation. METHODS: Patients with early persistent atrial fibrillation who underwent the first radiofrequency ablation procedure were retrospectively analyzed. The electrocardiographic, echocardiographic and clinical data of the enrolled patients before and after operation were collected and recorded. After adjusting confounding factors and performing stratified analysis, the association between the P wave duration and the atrial fibrillation recurrence of patients with early persistent atrial fibrillation after radiofrequency ablation was explored. RESULTS: The proportions of atrial fibrillation recurrence of the low, medium, and high P wave duration groups were 6.4%, 19.7%, and 47.0%, respectively. After potential confounding factors were adjusted, the risk of atrial fibrillation recurrence gradually increased with the increase of P wave duration (odds ratio: 1.093, 95% confidence interval: 1.063-1.124, p < 0.001). This trend was statistically significant (odds ratio: 1.099, 95% confidence interval: 1.052-1.149, p < 0.001), especially in comparison of high vs. low (odds ratio: 16.99, 95% confidence interval: 4.75-60.78, p < 0.001). Curve fitting showed that there was a linear and positive association between the P wave duration and the risk of atrial fibrillation recurrence. This association was consistent in different subgroups based on gender, drinking, history of smoking, hypertension, diabetes mellitus, peripheral artery disease, stroke or transient ischemia attack, hyperlipidemia, heart failure, and heart rate, suggesting that there was no significant interaction between different grouping parameters and the association (p for interaction range = 0.217-0.965). CONCLUSIONS: In patients with early persistent atrial fibrillation who underwent radiofrequency ablation procedure for the first time and converted to sinus rhythm, the P wave duration within 72 h after the procedure was independently associated with the risk of atrial fibrillation recurrence, and such association was linear and positive.

An echocardiographic model for predicting the recurrence of paroxysmal atrial fibrillation after circumferential pulmonary vein ablation.

BACKGROUND: Atrial fibrillation (AF) is a highly prevalent arrhythmia, with substantial associated morbidity and mortality. Circumferential pulmonary vein ablation (CPVA) is an effective rhythm control strategy, however, recurrence is an important factor influencing treatment decisions. HYPOTHESIS: To develop a predictive model based on left atrial (LA) structure and function, and evaluate its efficiency in predicting the recurrence of AF after CPVA. METHODS: Patients with paroxysmal AF who underwent CPVA were enrolled in this study and randomly divided into a development set and a validation set. The clinical and echocardiographic data of each patient were collected. In the development set, a least absolute shrinkage and selection operator (LASSO) regression was used to establish a LA ultrasound feature. By combining that LA ultrasound feature with independent clinical risk factors, we established an echocardiographic model using multivariate logistic regression and plotted the corresponding nomogram. RESULTS: The LA ultrasound feature established by LASSO regression included nine echocardiographic indicators related to LA structure and function. It also exhibited good predictive ability in both the development set and the validation set (AUC:0.944, 95%CI: 0.910-0.978; AUC:0.878, 95%CI: 0.816-0.942). Logistic regression analysis indicated that LA ultrasound feature and AF duration were independent predictors for AF recurrence. The combined model including LA ultrasound feature and AF duration also showed good discriminability in both the development set (AUC: 0.950, 95% CI:0.914-0.985) and the validation set (AUC: 0.890, 95% CI: 0.831-0.949). The calibration curve showed good agreement between the predicted value and observed value. CONCLUSIONS: Our model that is based on LA structure and function measured by echocardiography is a useful non-invasive preoperative tool, which exhibits good accuracy in predicting the recurrence of AF after CPVA.