Development of hair cells in inner ear is associated with expression and promoter methylation of Notch-1 in postnatal mice.

The present study was designed to investigate the correlation among the number of hair cells in inner ear, Notch-1 gene expression levels and its methylation status of the promoter region in the postnatal mice. The hair cells in inner ear were collected from postnatal mice at day 0, 4, 8 and 16 and counted by immunofluorescence. Notch-1 mRNA expression were measured by real-time quantitative polymerize chain reaction (PCR). Methylation levels of CpG islands in Notch-1 promoters were analyzed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry. The results showed that the number of hair cells in the inner ear increased gradually after birth, which were positively correlated to Notch-1 mRNA expression. However, analysis on methylation of CpG sites in Notch-1 promoter showed that the methylation rates increased gradually after births, which were correlated with the decreased expression of Notch-1. Drug lesion induced the loss of hair cells, and stimulated the expression of Notch-1 mRNA expression, but didn't influence the methylation rates of Notch-1 promoter. We concluded that the Notch-1 mRNA expression level in inner ear tissues is correlated with the development of hair cells. CpG islands in Notch-1 promoter region manifest hypermethylation status when hair cells in inner ear are mature.

A Prospective Study of the Surgical Outcome of Simple Uvulopalatopharyngoplasty (UPPP), UPPP Combined With Genioglossus Advancement or Tongue Base Advancement for Obstructive Sleep Apnea Hypopnea Syndrome Patients With Multilevel Obstruction.

OBJECTIVES: To investigate the surgical outcomes of different uvulopalatopharyngoplasty (UPPP). METHODS: All subjects underwent overnight polysomnography and were evaluated using the Epworth sleepiness scale (ESS), the Quebec sleep questionnaire and the snoring scale at the baseline and 3 and 12 months following operation. The primary endpoint was the overall effective rate representing the sum of the surgical success rate and effective rate. RESULTS: The overall effective rate at 12 months post surgery was 55.6% for simple UPPP, 95.8% for UPPP+GA, and 92.3% for UPPP+TBA. The surgical success rate at 3 and 12 months postoperation for UPPP+GA or UPPP+TBA was significantly higher than simple UPPP (P<0.05). Marked improvement was observed in all patients in the snoring scale score and the ESS score 3 and 12 months following surgery compared to the baseline (P<0.05 in all). CONCLUSION: UPPP, UPPP+GA, and UPPP+TBA are all effective in improving the surgical outcome of obstructive sleep apnea hypopnea syndrome (OSAHS) patients with multilevel obstruction. UPPP+TBA appears to be the most effective in treating OSAHS patients.

Characterization of upper airway obstruction by fiber-optic nasolaryngoscopy and MRI in preoperative OSAHS patients.

OBJECTIVE: To investigate changes in the upper airway and its surrounding soft tissue and to characterize the extent and severity of upper airway obstruction in 136 obstructive sleep apnea/hypopnea syndrome (OSAHS) patients who were awake. METHODS: OSAHS patients and healthy controls were evaluated by fiber-optic nasolaryngoscopy and MRI. The cross-sectional area and pharyngeal wall thickness of the retropalatal, retroglossal and epiglottic region were determined. RESULTS: Ninety-five percent of the mild OSAHS subjects had single-plane obstruction (vs. severe OSAHS, p < 0.05), 5.0% of the mild OSAHS subjects had two-plane obstruction (p < 0.05) and none of them had three-plane obstruction (p < 0.05). The cross-sectional area of the retropalatal, retroglossal and epiglottic region progressively declined as the severity of OSAHS increased (severe OSAHS vs. controls, p < 0.05). The lateral pharyngeal wall was significantly thicker in OSAHS subjects than in healthy controls (p < 0.05). The cross-sectional area of the soft palate in moderate and severe OSAHS subjects was markedly larger than that of the healthy controls (p < 0.05) and positively correlated with the apnea/hypopnea index (p < 0.05). CONCLUSION: Moderate and severe OSAHS patients exhibit multi-plane obstruction of the upper airway, particularly in the retropalatal and retroglossal region. The severity of OSAHS negatively correlates with the thickness, length and cross-sectional area size of the soft palate.

Changes in sleep characteristics and airway obstruction in OSAHS patients with multi-level obstruction following simple UPPP, UPPP-GA, or UPPP-TBA: a prospective, single-center, parallel group study.

OBJECTIVE: To investigate changes in S3 sleep and the apnea hypopnea index (AHI), SpO2 desaturation and CT90, and to determine changes in the degree of airway collapse and in the cross-sectional area of the retropalatal and lingual region in obstructive sleep apnea hypopnea syndrome patients. METHOD: All subjects underwent overnight polysomnography and were evaluated using Müller's test and magnetic resonance imaging at baseline, 3, and 12 months following surgery. RESULT: The mean S3 scores in patients receiving uvulopalatopharyngoplasty combined with genioglossus advancement (UPPP-GA) or UPPP combined with tongue base advancement using the Repose™ system (UPPP-TBA) noticeably increased. Marked improvement was seen in the mean AHI, LSO2, and CT90 scores 3 and 12 months following surgery compared to baseline. Airway collapsed by 25-50% in the greatest proportion undergoing surgery at the tongue base. CONCLUSION: UPPP-GA and UPPP-TBA more effectively improve S3 sleep, and mean AHI, LSO2, and CT90 scores. In addition, they effectively alleviate airway obstruction by improving the cross-sectional area of these regions.

The relationship between structural/MHC changes in upper airway palatopharyngeal muscle morphology and obstructive sleep apnea/hypopnea syndrome.

The aim of this study is to explore the relationship between structural/MHC changes in upper airway palatopharyngeal muscle morphology and obstructive sleep apnea/hypopnea syndrome. Palatopharyngeal muscle specimens were taken from 51 patients with obstructive sleep apnea hypopnea syndrome (OSAHS) who underwent uvulopalatopharyngoplasty (UPPP) resection. Patients were divided into light, medium and severe in terms of the severity of their OSAHS. There were 17 patients in each severity group. Palatopharyngeal muscle specimens were also taken from 17 patients suffering from chronic tonsillitis for comparison as the control group. All specimens were stained using Masson and observed for structural changes, especially in muscle fiber morphology, density and arrangement, as well as intermuscular connective tissues, under light microscopy. All specimens were also analyzed for MHC-I, MHC-IIa and MHC-IIb phenotype and protein expression differences using mRNA quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence staining. The results from each group were then statistically analyzed using semi-quantitative analysis. Light microscopy with Masson staining revealed that in the control group, the muscle fibers are closely connected and arranged neatly. In specimens from patients suffering from OSAHS, the palatopharyngeal muscle fibers are larger with obvious hypertrophy and there was an increase in elastic fibers. The mucosal lamina propria was thickened, and the density of muscle fibers was reduced. Muscle fibers are not neatly arranged and degeneration was observed. The amount of muscular pathology and fibrosis corresponds to the severity of disease in the patients. In patients with severe OSAHS, the proportion of collagen to muscle fibers was increased significantly. Immunofluorescence results reveal that there were significantly more fast muscle fibers and less slow muscle fibers in the study group than the control group. mRNA quantitative reverse transcription polymerase chain reaction (RT-PCR) revealed similar results, i.e., the proportion of MHC-II palatopharyngeal muscle fibers is higher in the study group than the control group, and increases with the severity of OSAHS. Pathological change occurs in both the collagen and muscle of OSAHS patients and corresponds to the degree of severity of OSAHS. Pathological change in palatopharyngeal muscle tissues is therefore, likely to be related to the occurrence and development of OSAHS. The increase in the proportion of the MHC-1I type fibers in OSAHS patients is likely to have an effect on the amount of airway support conferred by the muscle. This is likely the reason behind the lack of clinical improvement in some patients with severe OSAHS despite surgical treatment.