Effect of exercise versus mandibular advancement device in moderate obstructive sleep apnea patients with mandibular retrognathia: A randomized clinical trial.

OBJECTIVE: The aim of this study was to investigate the effects of exercise and mandibular advancement device (MAD) on severity of Obstructive sleep apnea syndrome (OSAS) with mandibular retrognathia. METHODS: Patients were randomly allocated into either exercise group or MAD group. All patients underwent blood tests, polysomnography studies and questionnaires studies at enrollment and at the 12-week's follow-up. RESULTS: Our study showed MAD was superior to exercise in improving polysomnographic outcomes and Snore Scale (SS) score. No significant difference was observed between the two treatments in terms of Epworth Sleepiness Scale (ESS) score. Moreover, in the exercise group, improvements were also observed in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). CONCLUSION: MAD was more effective than exercise in improving sleep efficiency. Exercise can improve daytime sleepiness and lipid metabolism, independent of the effects on BMI.Trial registration ChiCTR2000034188.

Effectiveness of Continuous Positive Airway Pressure Versus Mandibular Advancement Device in Severe Obstructive Sleep Apnea Patients With Mandibular Retrognathia: A Prospective Clinical Trial.

AIM: Some obstructive sleep apnea (OSA) patients may have mandibular retrognathia (ANB > 4.7° and SNB < 76.2°). Currently, there are no studies that have compared the effectiveness of continuous positive airway pressure (CPAP) versus mandibular advancement device (MAD) in severe OSA patients with mandibular retrognathia. We explored the efficacy of CPAP versus MAD for the treatment of severe OSA patients with mandibular retrognathia. METHODS: A total of 105 patients were enrolled. Outcomes were assessed by using polysomnography, Epworth Sleepiness Scale (ESS), Snore Scale (SS), Self-rating Anxiety Scale (SAS), and compliance, before treatment and after 6 and 12 months of treatment. RESULTS: Continuous positive airway pressure was superior to MAD in improving polysomnographic outcomes and SS score, but reported compliance was higher on MAD. There is no significant difference between the 2 treatments in terms of ESS score and SAS score. Obstructive sleep apnea patients with mandibular retrognathia showed greater improvement than those without mandibular retrognathia in terms of apnea-hypopnea index and oxygen desaturation index after MAD. CONCLUSION: Continuous positive airway pressure and MAD are both effective in treating severe OSA patients with mandibular retrognathia. Mandibular advancement device is a good alternative to CPAP in severe OSA patients with mandibular retrognathia. Mandibular advancement device is more effective in treating OSA patients with mandibular retrognathia than those without. Trial registration: ChiCTR2000032541.

Cigarette smoking promotes keratinocyte malignancy via generation of cancer stem-like cells.

Objectives: Cigarette smoking is involved in the pathogenesis of head and neck squamous cell carcinoma (HNSCC). However, the underlying molecular mechanisms of cigarette smoking-induced HNSCC carcinogenesis are unclear and may involve cancer stem-like cell generation. We examined the effects of cigarette smoke condensate (CSC) on the formation of cancer stem-like cells, which are rich in octamer-binding transcription factor (OCT)-4, inhibitor of differentiation 1 (ID1), nuclear factor (NF)-κB, and B lymphoma Mo-MLV insertion region 1 homolog (BMI-1). Materials and Methods: We used in vitro, in vivo, and archival human HNSCC tissue analysis to evaluate the effects of CSC on cancer stem-like cell formation. Results: We found that CSC regulated OCT-4 expression, which subsequently regulated ID1 and NF-κB, at the promoter, mRNA, and protein levels in vitro. Furthermore, OCT-4 knockdown with siRNA reduced ID1 expression. ID1 and NF-κB synergistically increased the expression of BMI-1 and stimulated keratinocyte sphere generation. In vivo, ID1 and NF-κB acted together to generate malignant xenograft tumors, which were aggressive locally and systemically metastatic. Clinical data confirmed that ID1- and NF-κB-positive patients had poor clinical outcomes and 5-year disease-free survival. Conclusion: Our data suggest that smoking cigarettes promoted cancer stem-like cell generation in the head and neck area via the OCT-4/ID1/NF-κB/BMI-1 signaling pathway.

Prognostic nomogram based on immune scores for laryngeal squamous cell cancer.

PURPOSE: Immune scores have been used as a prognostic factor for various types of cancer. However, the association between immune scores and the prognosis of laryngeal squamous cell cancer (LSCC) has not yet been investigated. This study aimed to explore the prognostic significance of immune scores and construct a clinical nomogram to predict the survival of patients with LSCC. METHODS: The clinicopathological characteristics and immune scores of 102 patients with LSCC were obtained from TCGA database and a nomogram was developed. C-index and calibration curves were applied to assess the performance of the model. RESULTS: Patients with higher immune scores had significantly better overall survival (OS). The prognostic nomogram presented a good performance in survival prediction. CONCLUSIONS: High immune scores are correlated with improved OS in patients with LSCC. In addition, the nomogram developed for this study may assist clinicians in the prognostic evaluation of patients with LSCC.

Identification of core biomarkers associated with pathogenesis and prognostic outcomes of laryngeal squamous-cell cancer using bioinformatics analysis.

PURPOSE: Despite advances in the treatment of laryngeal squamous-cell carcinoma (LSCC), the survival rate of LSCC remains poor. Thereby, it is urgent to identify novel diagnostic and prognostic biomarkers for LSCC. The study aimed to identify potential core genes associated with the pathogenesis and prognosis of LSCC. METHODS: Differentially expressed genes between LSCC and normal laryngeal tissue samples were screened by an integrated analysis of data from GEO and TCGA databases. Core genes related to the pathogenesis and prognosis of LSCC were identified by employing protein-protein interaction network and Cox proportional hazards model analyses. RESULTS: Ten hub genes (AURKA, AURKB, CDC45, KIF2C, NDC80, EXO1, TYMS, RAD51AP1, ITGA3, and UBE2T) that might be highly related to the pathogenesis of LSCC were identified. An eight-gene prognostic signature consisted of ZG16B, STATH, RTN4R, MSRA, CBX8, SLC5A1, EFNB1 and CNTFR was constructed with a good performance in predicting overall survivals. CONCLUSION: Our findings might shed some new light on the pathogenesis of LSCC and help identify new therapeutic targets of LSCC.

Combined α-programmed death-1 monoclonal antibody blockade and fractionated radiation therapy reduces tumor growth in mouse EL4 lymphoma.

The programmed death (PD) pathway is frequently present in the tumor microenvironment (TME) and suppresses tumor immunity by inhibiting the activity of tumor-infiltrating lymphocytes (TILs), particularly, CD8+ lymphocytes. PD immunotherapy involves stimulation of the immune response in the region surrounding the tumor but is insufficient to prevent tumor progression. Therefore, in this study, we examined the effects of combined PD immunotherapy with fractionated radiotherapy (RT) on antitumor immunity and tumor growth in lymphoma. The immune cell profiles of the TME, blood, and secondary lymphoid organs were determined 7 days after treatment. Four combination therapies were compared. The synergistic effects of αPD-1 mAb and fractionated RT on increased CD8+ lymphocytes in the TME, blood, and secondary lymphoid organs led to substantial tumor regression in mouse EL4 lymphoma, both locally and systemically. Fractionated RT for 4 days followed by αPD-1 mAb therapy was significantly superior to other schemes in terms of overall survival rates and curative rates in xenograft model mice. Our data indicated that substantial immune responses occurred following combination therapy with fractionated RT and αPD-1 mAb immunotherapy. Our findings provide important insights into the use of RT plus αPD-1 mAb as an efficacious combinatorial therapy.

Epidermal growth factor receptor mutations in Chinese patients with laryngeal squamous cell carcinoma.

CONCLUSION: The epidermal growth factor receptor (EGFR) mutation is rare in patients with laryngeal squamous cell carcinoma (LSCC) in China. OBJECTIVE: To determine the incidence of EGFR mutations in patients with LSCC who underwent surgical resection in mainland China. METHODS: xTAG technology was used to detect the EGFR exon 19, exon 20, and exon 21 mutations in 132 patients with LSCC who underwent surgical treatment in our hospital from 2010 to 2013. RESULTS: Of the 132 LSCC specimens examined, only 1 specimen was found to be positive for EGFR exon 20 mutation (0.76%). The mutation was p.T790M in exon 20. Two LSCC specimens were positive for EGFR exon 21 mutation (1.52%). The mutation was p.L858R in exon 21. None of the samples was found to be positive for EGFR exon 19 mutation.

Effects of budesonide on the expression of the glucocorticoid receptor-α in nasal polyp epithelial cells.

BACKGROUND: This study explores effects of budesonide on the proliferation of nasal polyp epithelial cells and expression of the glucocorticoid receptor (GR) alpha in nasal polyp epithelial cells. METHODS: Primary cultured, purified, and identified the epithelial cells collected from nasal polyps. The proliferation of nasal polyp epithelial cells was examined by a cell counting kit, and expression of GR-alpha mRNA in nasal polyp epithelial cells was examined by reverse transcription polymerase chain reaction, after training nasal polyp epithelial cells in budesonide solution. RESULTS: The average survival rate of nasal polyp epithelial cells was the lowest in 1 × 10(-6) M budesonide solution (29.284 ± 0.311%), compared with other concentrations. Budesonide at 1 × 10(-8) M caused down-regulation of GR-alpha mRNA expression levels at 6 and 12 ours, compared with the 0-hour group (p < 0.001); compared with the 0-hour group, there were significantly lower expression levels of GR-alpha mRNA at both 24 and 48 hours (p < 0.001); Expression of GR-alpha mRNA at either 48 or 12 hours was not significantly different from that at 24 hours. CONCLUSION: Budesonide can significantly inhibit the proliferation of nasal polyp epithelial cells, down-regulate the expression of GR-alpha mRNA in nasal polyp epithelial cells with time dependence.

Expression of HMGA1 and ezrin in laryngeal squamous cell carcinoma.

CONCLUSION: The overexpression of HMGA1 or Ezrin may contribute to the carcinogenesis, development, and metastasis of laryngeal squamous cell carcinoma (LSCC). OBJECTIVE: To investigate the expression of HMGA1 and Ezrin in LSCC and analyze their clinical significance. METHODS: The expression of HMGA1 and Ezrin was analyzed by immunohistochemistry (IHC) in 50 cases of LSCC. Thirty cases of laryngeal polyp and 30 cases of atypical hyperplasia of larynx were studied as controls. The expression of HMGA1 and Ezrin was analyzed by real-time PCR and by Western blot in 30 cases of LSCC; samples from adjacent normal epithelial tissues in 30 cases were studied as controls. RESULTS: (1) IHC revealed that the positive rate of HMGA1 protein was 68.0% (34/50), 53.3% (16/30), and 13. 3% (4/30) in LSCC, atypical hyperplasia of larynx, and laryngeal polyp (p < 0.05), and the positive rate of Ezrin protein was 64.0% (32/50), 50.0% (15/30), and 23.3% (7/30) (p < 0.01), respectively. (2) Real-time PCR demonstrated that the mean relative mRNA expression levels of HMGA1 in LSCC and in normal tissues were 2.41 ± 0.40 and 1.05 ± 0.18, respectively (p < 0.01). The mRNA levels of Ezrin in LSCC and in normal tissues were 1.79 ± 0.27 and 1.04 ± 0.22, respectively (p < 0.05). (3) Western blotting revealed that the mean relative protein expression levels of HMGA1 in LSCC and in normal tissues were 1.73 ± 0.60 and 0.35 ± 0.17, respectively (p < 0.01). The protein levels of Ezrin in LSCC and in normal tissues were 1.82 ± 0.77 and 0.42 ± 0.20, respectively (p < 0.01).

Numerical simulation for the upper airway flow characteristics of Chinese patients with OSAHS using CFD models.

OSAHS is a common disease with many factors related to the etiology. Airflow plays an important role in the pathogenesis of OSAHS. Previous research has not yielded a sufficient understanding of the relationship between airflow in upper airway and the pathophysiology of OSAHS. Therefore, a better understanding of the flow inside the upper airway in an OSAHS patient is necessary. In this study, ten Chinese adults with OSAHS were recruited. We used the software MIMICS 13.1 to construct 3-dimensional (3-D) models based on the computer tomography scans of them. The numerical simulations were carried out using the software ANSYS 12.0. We found that during the inhalation phase, the vortices and turbulences were located in both the anterior part of the cavity and nasopharynx. But there is no vortex in the whole nasal cavity during the expiratory phase. The airflow velocity is much higher than that of the normal models. The distributions of pressure and wall shear stress are different in two phases. The maximum velocity, pressure and wall shear stress (WSS) are located in velopharynx. It is notable that a strong negative pressure region is found in pharyngeal airway. The maximum velocity is 19.26 ± 12.4 and 19.46 ± 13.1 m/s; the average pressure drop is 222.71 ± 208.84 and 238.5 ± 218.56 Pa and the maximum average WSS is 0.72 ± 0.58 and 1.01 ± 0.61 Pa in inspiratory and expiratory, respectively. The changes of airflow due to the structure changes play an important role in the occurrence of collapse and obstruction of the upper airway, especially, the abnormal pressure changes in velopharyngeal during both inspiratory and expiratory phases. We can say that the airway narrowing in the pharynx may be one of the most important factors driving airway collapse. In addition, the most collapsible region of the pharyngeal airway of the patient with OSAHS may be the velopharynx and oropharynx. In spite of limitations, our results can provide a basis for the further research. On this basis, more about the secret of the pathogenesis of the OSAHS will be revealed.