Background Radiotherapy is the first-line regimen for treating oral squamous cell carcinoma (OSCC) in current clinics. However, the development of therapeutic resistance impacts the anticancer efficacy of irradiation in a subpopulation of OSCC patients. As a result, discovering a valuable biomarker to predict radiotherapeutic effectiveness and uncovering the molecular mechanism for radioresistance are clinical issues in OSCC. Methods Three OSCC cohorts from The Cancer Genome Atlas (TCGA), GSE42743 dataset and Taipei Medical University Biobank were enrolled to examine the transcriptional levels and prognostic significance of neuronal precursor cell-expressed developmentally downregulated protein 8 (NEDD8). Gene set enrichment analysis (GSEA) was utilized to predict the critical pathways underlying radioresistance in OSCC. The colony-forming assay was used to estimate the consequences of irradiation sensitivity after the inhibition or activation of the NEDD8-autophagy axis in OSCC cells. Results NEDD8 upregulation was extensively found in primary tumors compared to normal adjacent tissues and potentially served as a predictive marker for the therapeutic effectiveness of irradiation in OSCC patients. NEDD8 knockdown enhanced radiosensitivity but NEDD8 overexpression reduced it in OSCC cell lines. The inclusion of MLN4924, a pharmaceutical inhibitor for NEDD8-activating enzyme, dose-dependently restored the cellular sensitivity to irradiation treatment in irradiation-insensitive OSCC cells. Computational simulation by GSEA software and cell-based analyses revealed that NEDD8 upregulation suppresses Akt/mTOR activity to initiate autophagy formation and ultimately confers radioresistance to OSCC cells. Conclusion These findings not only identify NEDD8 as a valuable biomarker to predict the efficacy of irradiation but also offer a novel strategy to overcome radioresistance via targeting NEDD8-mediated protein neddylation in OSCC.
Objectives: To investigate the incidence of accessory maxillary sinus ostia in superior meatus in patients with clinical and radiological signs of maxillary sinusitis and the association with the development of chronic rhinosinusitis. Design: Retrospective study Setting: Tertiary care hospital Participant: 159 patients examined with paranasal sinus computed tomography scans Main outcome measures: We retrospectively evaluated patients who visited the outpatient department at an academic medical facility between January and April 2020 with a clinical diagnosis of chronic rhinosinusitis. Paranasal sinus axial and coronal computed tomography scans were evaluated for accessory maxillary sinus ostia in superior meatus and confirmed by reconstructed three-dimensional simulation images. The demographic information and incidence of accessory ostia in superior meatus were assessed. The Lund–Mackay score was used to rate chronic rhinosinusitis severity. Analysis of variance was performed to correlate the severity of chronic rhinosinusitis with presenting accessory ostia in superior meatus. Results: Of 159 patients (81 males; 78 females), 41.5% had accessory maxillary sinus ostia in superior meatus. Of these, two-thirds were bilateral and one-third was unilateral. The severity of rhinosinusitis was not correlated with having accessory maxillary sinus ostia in superior meatus, but the presence of accessory ostia was significantly associated with less severe chronic rhinosinusitis (P < 0.001). Conclusions: Accessory maxillary sinus ostia in superior meatus are significantly associated with less severe chronic rhinosinusitis and most cases are bilateral.
Hypoxemia and obstructive sleep apnea (OSA) have been recognized as a threat to life. Nonetheless, information regarding the association between pre-dialytic pulse oximeter saturation (SpO2) level, OSA and mortality risks remains mysterious in patients with maintenance hemodialysis (MHD). Bioclinical characteristics and laboratory features were recorded at baseline. Pre-dialytic SpO2 was detected using a novel microchip LED oximetry, and the Epworth Sleepiness Scale (ESS) score greater than 10 indicated OSA. Non-adjusted and adjusted hazard ratios (aHRs) of all-cause and cardiovascular (CV) mortality were analyzed for pre-dialytic SpO2, OSA and potential risk factors. During 2152.8 patient-months of follow-up, SpO2 was associated with incremental risks of all-cause and CV death (HR: 0.90 (95% CI: 0.82–0.98) and 0.88 (95% CI: 0.80–0.98), respectively). The association between OSA and CV mortality was significant (HR: 3.19 (95% CI: 1.19–9.38). In the multivariate regression analysis, pre-dialytic SpO2 still had an increase in all-cause and CV death risk (HR: 0.88 (95% CI: 0.79–0.98), 0.82 (95% CI: 0.71–0.96), respectively). Considering the high prevalence of silent hypoxia in the post COVID-19 era, a lower pre-dialytic SpO2 level and severe OSA warn clinicians to assess potential CV risks. In light of clinical accessibility, the microchip LED oximetry could be developed as a wearable device within smartphone technologies and used as a routine screen tool for patient safety in the medical system.
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