In inflammatory sites, high molecular weight hyaluronan fragments are degraded into lower molecular weight hyaluronan fragments (LMW-HA) to regulate immune responses. However, the function of LMW-HA in PTC progression remains to be elucidated. In this study, we found that receptor of LMW-HA, TLR4, was aberrantly overexpressed in PTC tissues and cell line W3. Exposure of W3 cells to LMW-HA promoted cell proliferation and migration via TLR4. Knockdown of TLR4 has provided evidence that TLR4 is essential for LMW-HA-induced CXCR7 expression, which is responsible for LMW-HA-induced proliferation and migration of W3 cells. In tumor-bearing adult nude mice, stimulation of LMW-HA on W3 cells promotes CXCR7 expression in tumor masses (P=0.002) and tumor growth (P<0.001). To further confirm our findings, we investigated the clinicopathologic significance of TLR4 and CXCR7 expression using immumohistochemistry in 135 human PTC tissues and 56 normal thyroid tissue samples. Higher rates of TLR4 (53%) and CXCR7 (24%) expression were found in PTC tissues than in normal tissues. Expression of TLR4 or CXCR7 is associated with tumor size and lymph node metastasis. Therefore, LMW-HA may contribute to the development of PTC via TLR4/CXCR7 pathway, which may be a novel target for PTC immunomodulatory therapy.

Background: Diabetes-induced cardiac fibrosis is one of the main mechanisms of diabetic cardiomyopathy. As a common histone methyltransferase, enhancer of zeste homolog 2 (EZH2) has been implicated in fibrosis progression in multiple organs. However, the mechanism of EZH2 in diabetic myocardial fibrosis has not been clarified.Methods: In the current study, rat and mouse diabetic model were established, the left ventricular function of rat and mouse were evaluated by echocardiography and the fibrosis of rat ventricle was evaluated by Masson staining. Primary rat ventricular fibroblasts were cultured and stimulated with high glucose (HG) in vitro. The expression of histone H3 lysine 27 (H3K27) trimethylation, EZH2, and myocardial fibrosis proteins were assayed.Results: In STZ-induced diabetic ventricular tissues and HG-induced primary ventricular fibroblasts in vitro, H3K27 trimethylation was increased and the phosphorylation of EZH2 was reduced. Inhibition of EZH2 with GSK126 suppressed the activation, differentiation, and migration of cardiac fibroblasts as well as the overexpression of the fibrotic proteins induced by HG. Mechanical study demonstrated that HG reduced phosphorylation of EZH2 on Thr311 by inactivating AMP-activated protein kinase (AMPK), which transcriptionally inhibited peroxisome proliferator-activated receptor γ (PPAR-γ) expression to promote the fibroblasts activation and differentiation.Conclusion: Our data revealed an AMPK/EZH2/PPAR-γ signal pathway is involved in HG-induced cardiac fibrosis.

Background: Paroxysmal supraventricular tachycardia (PSVT) is a common arrhythmia associated with palpitation and a decline in quality of life. However, it is undetectable with sinus-rhythmic ECGs when patients are not in the symptomatic onset stage. Methods: In the current study, a convolution neural network (CNN) was trained with normal-sinus-rhythm standard 12-lead electrocardiographs (ECGs) of negative control patients and PSVT patients to identify patients with unrecognized PSVT. PSVT refers to atrioventricular nodal reentry tachycardia or atrioventricular reentry tachycardia based on a concealed accessory pathway as confirmed by electrophysiological procedure. Negative control group data were obtained from 5107 patients with at least one normal sinus-rhythmic ECG without any palpitation symptoms. All ECGs were randomly allocated to the training, validation and testing datasets in a 7:1:2 ratio. Model performance was evaluated on the testing dataset through F1 score, overall accuracy, area under the curve, sensitivity, specificity and precision. Results: We retrospectively enrolled 407 sinus-rhythm ECGs of PSVT procedural patients and 1794 ECGs of control patients. A total of 2201 ECGs were randomly divided into training (n = 1541), validation (n = 220) and testing (n = 440) datasets. In the testing dataset, the CNN algorithm showed an overall accuracy of 95.5%, sensitivity of 90.2%, specificity of 96.6% and precision of 86.0%. Conclusion: Our study reveals that a well-trained CNN algorithm may be a rapid, effective, inexpensive and reliable method to contribute to the detection of PSVT.

Background: Remote magnetic navigation (RMN) is often used in combination with a 3‐dimensional mapping system to perform catheter ablations. This study aim to investigate the feasibility and effectiveness of a novel 3D‐mapping system, EnSite Precision, combined with RMN for catheter ablation of premature ventricular contractions (PVCs), and compared it to the procedures performed by CARTO3 with RMN.Methods: Forty‐three consecutive PVC patients were either ablated with the guidance of EnSite Precision (n = 22) or CARTO (n = 21) navigated by RMN. Procedure‐related details, acute and long‐term success were assessed.Results: Patient characteristics between both the groups were similar (age: 47.1 ± 19.8 vs 47.1 ± 12.7, female: 63.6% vs 57.1%). No significant difference was found in the procedure time (99.5 ± 30.4 vs 92.9 ± 24.8 min, P = 0.436), mapping time (18.6 ± 12.8 vs 15.5 ± 10.2 min, P = 0.390), radiofrequency ablation time (333.4 ± 267.0 vs 469.3 ± 343.1 s, P = 0.154), fluoroscopy time (4.0 ± 1.9 vs 3.8 ± 2.0 min, P = 0.635), and X‐ray dose (1.8 ± 1.4 vs 2.0 ± 1.2 Gycm², P = 0.649) between the two groups. No significant procedural complication occurred in either group. In addition, there was no significant differences regarding the acute success rate (90.9% vs 90.5%, P = 0.961) and long‐term success rate (86.4% vs 81.0%, P = 0.631) after 16.2 ± 6.2 months of follow‐up between the two groups.Conclusions: RMN combined with EnSite Precision mapping system is effective and safe for catheter ablation of PVCs.

Background: Concealed accessory pathway (AP) may cause atrial ventricular reentrant tachycardia impacting the health of patients. However, it is asymptomatic and undetectable during sinus rhythm.Methods: To detect concealed AP with electrocardiography (ECG) images, we collected normal sinus rhythmic ECG images of concealed AP patients and healthy subjects. All ECG images were randomly allocated to the training and testing datasets, and were used to train and test six popular convolutional neural networks from ImageNet pre‐training and random initialization, respectively.Results: We screened 152 ECG recordings in concealed AP group and 600 ECG recordings in control group. There were no statistically significant differences in ECG characteristics between control group and concealed AP group in terms of PR interval and QRS interval. However, the QT interval and QTc were slightly higher in control group than in concealed AP group. In the testing set, ResNet26, SE‐ResNet50, MobileNetV3_large_100, and DenseNet169 achieved a sensitivity rate more than 87.0% with a specificity rate above 98.0%. And models trained from random initialization showed similar performance and convergence with models trained from ImageNet pre‐training.Conclusion: Our study suggests that deep learning could be an effective way to predict concealed AP with normal sinus rhythmic ECG images. And our results might encourage people to rethink the possibility of training from random initialization on ECG image tasks.

Background. Perimitral atrial flutter (PMAFL) is one of the most common macro-reentrant left atrial tachycardias. Mitral isthmus (MI) linear ablation is a common strategy for the treatment of PMAFLs, and anterior septum (AS) linear ablation has emerged as a novel ablation approach. We aimed at assessing the effectiveness of AS linear ablation using robotic magnetic navigation for PMAFL ablation. Methods. In this retrospective study, a total of 36 consecutive patients presented with AFL as the unique arrhythmia or accompanied with atrial fibrillation (AF) who underwent catheter ablation were enrolled. Patients were classified into two groups according to the different ablation strategies, the MI line group (10 patients) and the AS line group (26 patients). Results. The clinical baseline characteristics of patients in the two groups were nearly identical. There were no significant differences in procedure time (148.7 ± 46.1 vs. 123.2 ± 30.1 min, ) or radiofrequency ablation time (25.9 ± 11.4 vs. 23.5 ± 12.6 min) between the two groups. Fluoroscopy time was longer in the MI line group (8.0 ± 4.4 vs. 5.1 ± 2.7 min, ), and the acute success rate was higher in the AS line group versus the MI line group (96.2% vs. 70%, ). The long-term freedom from arrhythmia survival rate was higher in the AS line group (73%) than in the MI line group (40%) after a mean follow-up time of 37.4 months with a 3-month blanking period ( ). Conclusions. AS linear ablation is an effective and safe strategy for PMAFL ablation using robotic magnetic navigation.