[Analysis of 30 cases of inherited cardiac arrhythmia syndrome in children].

Objective: To analyze and summarize the diagnosis and treatment experience of common inherited cardiac arrhythmia syndrome in pediatric patients, and explore the most appropriate therapy. Methods: A retrospective review identified 30 pediatric cases (19 males, 11 females) diagnosed with long QT syndrome (LQTS), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), hypertrophic cardiomyopathy (HCM), arrhythmogenc right ventricular cardiomyopathy (ARVC) from January 2008 to December 2018 in the Pediatric Cardiology Department, Guangdong Provincial People's Hospital. Data obtained included the diagnosis, treatment and follow-up outcome. Results: The most common inherited cardiac arrhythmia syndromes were LQTS (n=14) including 1 case with epilepsy, CPVT (n=5), HCM (n=7), ARVC (n=1), and BrS (n=3). Twenty-seven cases were admitted to hospital due to syncope, whereas the remaining 3 cases of BrS had not presented with syncope before admission. The average onset age of inherited arrhythmia was (10.0±3.3) years. Genetic testing was performed on 20 patients. The median follow-up time was 40 months. Among 15 patients who underwent implantable cardioverter defibrillator (ICD) and survived, 2 patients had frequent ICD discharge. One patient underwent radiofrequency ablation, and the other one received left cardiac sympathetic denervation and an increased ICD defibrillation threshold, and the number of ICD discharge was significantly reduced. Among 10 patients who received drug therapy, 4 patients including two patients who discontinued treatment without advices died. Two patients whose parents refused treatment died, 1 case diagnosed with unexplained sudden cerebral death, and the remaining 2 cases without indication for drug therapy survived without any treatment. Conclusions: Mortality rate is high in pediatric patients with inherited cardiac arrhythmia and syncope. The therapeutic effect of drugs are not satisfactory, ICD implantation is the most effective treatment to prevent sudden cardiac death currently, but the postoperative frequent discharge should be brought to the forefront and handled in time.

[A long-term follow-up study of cardiac resynchronization therapy for children with right ventricle-paced heart failure].

Objective: To evaluate the long-term effects of cardiac resynchronization therapy (CRT) in children with right ventricle-paced heart failure. Methods: Five children with chronically right ventricular-paced heart failure underwent operation of upgrading to CRT in Guangdong Cardiovascular Institute between July 2009 to January 2015. The first time the patients were implanted with endocardial permanent pacemaker was (11.6±4.6) years old. The New York Heart Association (NYHA) functional classification, QRS duration, left ventricular end diastolic diameter (LVDd), left ventricular ejection fraction (LVEF), standard deviation of peak systolic time of left ventricular wall (TS-SD) and follow-up data were retrospectively analyzed. Comparison between pre-and post-operation was performed using paired t test. Results: CRT significantly improved the NYHA class to Ⅰ-Ⅱdegree, reduced the QRS duration ((126±9)vs. (182±21)ms, t=-7.480, P=0.002) and the Z-score of LVDd (2.8±1.1 vs. 4.7±0.9, t=-2.880, P=0.045), and increased the LVEF (43%±10% vs. 28%±6%, t=3.350, P=0.029). No significant difference was found regarding the TS-SD ((48±17)vs. (95±41)ms, t=-2.240, P=0.090) pre- and post-CRT. The longest follow-up period was 9 years. During follow-up, 1 case died of ventricular fibrillation 2 years after upgrading, and 2 cases underwent CRT replacement due to battery depletion 7.2 years and 5.8 years after upgrading, respectively. Conclusion: CRT could be considered for children with chronically right ventricular-paced heart failure and improve heart function significantly.

p62/SQSTM1 enhances breast cancer stem-like properties by stabilizing MYC mRNA.

Aberrant p62 overexpression has been implicated in breast cancer development. Here, we found that p62 expression was elevated in breast cancer stem cells (BCSCs), including CD44+CD24- fractions, mammospheres, ALDH1+ populations and side population cells. Indeed, short-hairpin RNA (shRNA)-mediated knockdown of p62 impaired breast cancer cells from self-renewing under anchorage-independent conditions, whereas ectopic overexpression of p62 enhanced the self-renewal ability of breast cancer cells in vitro. Genetic depletion of p62 robustly inhibited tumor-initiating frequencies, as well as growth rates of BCSC-derived tumor xenografts in immunodeficient mice. Consistently, immunohistochemical analysis of clinical breast tumor tissues showed that high p62 expression levels were linked to poorer clinical outcome. Further gene expression profiling analysis revealed that p62 was positively correlated with MYC expression level, which mediated the function of p62 in promoting breast cancer stem-like properties. MYC mRNA level was reduced upon p62 deletion by siRNA and increased with p62 overexpression in breast cancer cells, suggesting that p62 positively regulated MYC mRNA. Interestingly, p62 did not transactivate MYC promoter. Instead, p62 delayed the degradation of MYC mRNA by repressing the expression of let-7a and let-7b, thus promoting MYC mRNA stabilization at the post-transcriptional level. Consistently, let-7a and let-7b mimics attenuated p62-mediated MYC mRNA stabilization. Together, these findings unveiled a previously unappreciated role of p62 in the regulation of BCSCs, assigning p62 as a promising therapeutic target for breast cancer treatments.

Knockdown of S100A4 chemosensitizes human laryngeal carcinoma cells in vitro through inhibition of Slug.

OBJECTIVE: S100A4 and Slug are known to be closely involved in resistance to chemotherapy. Furthermore, Slug signal was regulated by S100A4. Targeted therapy reducing S100A4 expression and Slug pathway activity may overcome the chemoresistance of human cancers. We hypothesized that over-expression of S100A4 and Slug was associated with the resistance to cisplatin of laryngeal carcinoma Hep-2 cells. We explored whether S100A4 silencing inhibited Slug, resulting in sensitization of laryngeal carcinoma Hep-2 cells to cisplatin. MATERIALS AND METHODS: We investigated the effects of S100A4 and Slug silencing by siRNA transfection on chemosensitivity to cisplatin (DDP) in Hep-2 cells in vitro. In order to confirm the correlation between S100A4 and Slug signals, siRNA transfected Hep-2 cells were over-expressed by pSlug transfection, then explored the effect of S100A4 silencing on chemosensitivity to cisplatin (DDP) in Hep-2 cells in vitro. Real-time RT-PCR and Western blotting confirmed the presence of S100A4 mRNA, Slug mRNA and proteins in Hep-2 cells. RESULTS: We found that resistance or insensitivity of Hep-2 cells to cisplatin might be associated with S100A4 and Slug expression. Knockdown of S100A4 and Slug markedly enhanced the cisplatin-induced suppression of Hep-2 cell growth and increased apoptosis. Knockdown of S100A4 may significantly reduce the levels of S100A4 mRNA, Slug mRNA and proteins, in cisplatin-treated Hep-2 cells. Re-expression of Slug in S100A4 siRNA transfected Hep-2 cells restored the cisplatin resistance in the Hep-2 cells. CONCLUSIONS: Overexpression of S100A4 may be associated with the resistance to cisplatin of laryngeal carcinoma Hep-2 cells. Knockdown of S100A4 enhances the sensitivity to cisplatin of laryngeal carcinoma cells via inhibition of Slug expression.