Background: Mutations in PAX3 cause Waardenburg syndrome (WS), but the mechanism remains unclear. Results: PAX3 binds mitotic chromosomes using its homeodomain (HD), a process that depends on arginine methylation and is lost in WS. Conclusion: PAX3 with mutations in HD causes WS by failing to load on mitotic chromosomes. Significance: This study pinpoints the molecular defects of a specific group of PAX3 WS mutants.

Hypopharyngeal squamous cell carcinoma (HSCC) is usually diagnosed at an advanced stage, leading to a poor prognosis. Even after improvement of surgical techniques, chemotherapy, and radiation technology, the survival rate of HSCC remains poor. Metformin, which is commonly used for type 2 diabetes mellitus (DM), has been suggested to reduce the risk of various cancer types. However, only a few clinical studies mentioned the relationship between metformin use and HSCC. Hence, the aim of this study was to elucidate the specific effect and mechanism of action of metformin in hypopharyngeal cancer. We first assessed whether metformin use has an effect on hypopharyngeal cancer patients with DM by conducting a retrospective cohort study. Our results showed that DM hypopharyngeal cancer patients who used metformin exhibited significantly better overall survival rates than that without metformin treatment. The cell-based analysis further indicated that metformin treatment regulated p38/JNK pathway to reduce Cyclin D1 and Bcl-2 expressions. In addition, metformin activated the pathways of AMPKα and MEK/ERK to phosphorylate p27(Thr198) and reduce mTOR phosphorylation in cells. These actions direct cells toward G1 cell cycle arrest, apoptosis, and autophagy. Our results, through combining a clinical cohort analysis with an in vitro study, demonstrate that metformin can be used for drug repositioning in the treatment of DM patients with hypopharyngeal cancer.

The objective was to investigate whether tongue base suspension with uvulopalatopharyngoplasty (UPPP) is beneficial on polysomnography analysis for sleep quality in patients with obstructive sleep apnea (OSA) anatomically classified as Fujita type III (small tonsils and a bulky tongue base). In the retrospective study, the charts of 36 patients with OSA that underwent tongue base suspension with UPPP from 2012 through 2015 were reviewed. The surgical outcome measured according to Sher’s classification (AHI reduction > 50% and AHI < 20 per hour as success group, otherwise as failure group). The pre- and post-operative sleep quality parameters were evaluated, and the total sleep time changes were evaluated based on electroencephalography study, slow wave sleep, sleep efficiency, rapid eye movement sleep percentile, and Epworth sleep scale scores. Respiratory, the outcomes of polysomnography analysis were then compared between the successful surgery and surgical failure groups during a 1-year follow up. Total arousals and reduced respiratory arousal indices, along with unchanged periodic leg movement and spontaneous electroencephalography arousal indices, were observed in the successful surgery group but not in the surgical failure group. There were 66% resulted in surgical success by this surgery, and 34% as in failure group according to Sher’s criteria. Patient sleep quality was further improved by reducing the respiratory arousal index and increasing the rapid eye movement sleep percentile during the 1-year follow up.