BACKGROUND:Nasopharyngeal carcinoma (NPC) is a type of malignant tumor with high morbidity. Aberrant levels of N7-methylguanosine (m7G) are closely associated with tumor progression. However, the characteristics of the tumor microenvironment (TME) in NPC associated with m7G modification remain unclear. METHODS:A total of 68,795 single cells from single-cell RNA sequencing data derived from 11 NPC tumor samples and 3 nasopharyngeal lymphatic hyperplasia (NLH) samples were clustered using a nonnegative matrix factorization algorithm according to 61 m7G RNA modification regulators. RESULTS:The m7G regulators were found differential expression in the TME cells of NPC, and most m7G-related immune cell clusters in NPC tissues had a higher abundance compared to non-NPC tissues. Specifically, m7G scores in the CD4+ and CD8+ T cell clusters were significantly lower in NPC than in NLH. T cell clusters differentially expressed immune co-stimulators and co-inhibitors. Macrophage clusters differentially expressed EIF4A1, and high EIF4A1 expression was associated with poor survival in patients with head and neck squamous carcinoma. EIF4A1 was upregulated in NPC tissues compared to the non-NPC tissues and mainly expressed in CD86+ macrophages. Moreover, B cell clusters exhibited tumor biological characteristics under the regulation of m7G-related genes in NPC. The fibroblast clusters interacted with the above immune cell clusters and enriched tumor biological pathways, such as FGER2 signaling pathway. Importantly, there were correlations and interactions through various ligand-receptor links among epithelial cells and m7G-related TME cell clusters. CONCLUSION:Our study revealed tumor-associated characteristics and immune dysregulation in the NPC microenvironment under the regulation of m7G-related TME cells. These results demonstrated the underlying regulatory roles of m7G in NPC.

ABSTRACTPurposePositive airway pressure (PAP) is the primary treatment for obstructive sleep apnea (OSA). This study aims to predict the optimal PAP pressure in Chinese OSA patients by their polysomnography (PSG) variables and demographic characteristics.MethodsPatients with an apnea–hypopnea index (AHI) ≥ 15 times/h who received PAP therapy (residual AHI < 5 times/h) and underwent PSG were included in this study. Sex, age, body mass index (BMI), Epworth Sleepiness Scale (ESS), AHI, supine AHI, lowest oxygen saturation (LSaO2), percentage of total sleep time spent with SaO2 < 90% (CT90), and PAP pressure were recorded. PAP pressure and other variables were analyzed using univariate correlation and multivariate linear stepwise regression analysis.ResultsA total of 167 patients were enrolled, with 122 in the study group and 45 in the validation group. Univariate correlation analysis revealed a significant correlation between PAP pressure and age, BMI, ESS, AHI, supine AHI, LSaO2, and CT90. The multivariate linear regression analysis showed that PAP pressure was correlated with gender (b = 1.142, p = 0.032), age (b = −0.039, p = 0.005), AHI (b = 0.047, p = 0.000), and CT90 (b = 0.037, p = 0.000). The final PAP pressure prediction equation was PAPpre (cmH2O) = 8.548 + 1.142 × sex −0.039 × age + 0.047 × AHI + 0.037 × CT90 (R2 = 0.553) (male is defined as 0 and female as 1). This model accounts for 55.3% of the optimal pressure variance, and the area under the ROC curve of PAP prediction pressure is 0.7419.ConclusionPSG variables can be used to predict PAP pressure in Chinese OSA patients, but for some individuals, the prediction model is not very good. PAP is correlated with age, BMI, ESS, AHI, supine AHI, LSaO2, and percentage of total sleep time spent with SaO2 < 90% (CT90), which can be used to predict the optimal PAP pressure.

INTRODUCTION:Many scales are designed to screen for obstructive sleep apnoea-hypopnoea syndrome (OSAHS); however, there is a lack of an efficiently and easily diagnostic tool, especially for Chinese. Therefore, we conduct a cross-sectional study in China to develop and validate an efficient and simple clinical diagnostic model to help screen patients at risk of OSAHS.METHODS:This study based on 782 high-risk patients (aged >18 years) admitted to the Sleep Medicine department of the Sixth Affiliated Hospital, Sun Yat-sen University from 2015 to 2021. Totally 34 potential predictors were evaluated. We divided all patients into training and validation dataset to develop diagnostic model. The univariable and multivariable logistic regression model were used to build model and nomogram was finally built.RESULTS:Among 602 high-risk patients with median age of 46 (37, 56) years, 23.26% were women. After selecting using the univariate logistic model, 15 factors were identified. We further used the stepwise method to build the final model with five factors: age, BMI, total bilirubin levels, high Berlin score, and symptom of morning dry mouth or mouth breathing. The AUC was 0.780 (0.711, 0.848), with sensitivity of 0.848 (0.811, 0.885), specificity of 0.629 (0.509, 0.749), accuracy of 0.816 (0.779, 0.853). The discrimination ability had been verified in the validation dataset. Finally, we established a nomogram model base on the above final model.CONCLUSION:We developed and validated a predictive model with five easily acquire factors to diagnose OSAHS patient in high-risk population with well discriminant ability. Accordingly, we finally build the nomogram model.

Objective Head and neck squamous cell carcinoma (HNSCC) is a highly heterotopic malignant tumor. Alternative splicing (AS) and RNA modification have been reported to be involved in tumorigenesis. Therefore, we constructed RNA modification-associated AS (RMA-AS) signature model to predict the prognosis of HNSCC. Methods AS events and RNA-modified gene expression information were downloaded from TCGA-HNSCC database. Univariate Cox regression analysis was employed for analyzing prognosis-related AS events. RMA-AS events were obtained by constructing a coexpression network between RNA modification-associated genes and AS events using WGCNA package. The prognostic signatures were analyzed by LASSO, univariate Cox, and multivariate Cox regression. Kaplan-Meier survival analysis, proportional hazard model, and ROC curve were performed to verify the prognostic value. “ESTIMATE” R package, ssGSEA algorithm, and CIBERSORT method were used to detect immune microenvironment in HNSCC. Cytoscape was utilized to build a regulatory network of splicing factor-regulated RMA-AS. Results There were 16,574 prognostic AS events and 4 differentially expressed RNA modification-associated genes in HNSCC. Based on RMA-AS events, we obtained a risk model consisting of 14 AS events, named RMA-AS_Score. The samples were divided into RMA-AS_Score high- and RMA-AS_Score low-risk groups, according to the risk score. The RMA-AS_Score high group was related to poor prognosis. Moreover, the RMA-AS_Score signature was an independent prognostic predictor and was related to tumor grade. Meanwhile, the AUC value of RMA-AS_Score was 0.652, which is better than other clinical characteristics. Besides, a nomogram prediction model of quantitative prognosis has also been developed, which has robust effectiveness in predicting prognosis. In addition, the prognostic signature was observably related to immune microenvironment and immune checkpoint. Finally, 14 splicing factors were identified and constructed into a network of splicing factor-regulated RMA-AS. Conclusion We identified the RMA-AS signature of HNSCC. This signature could be treated as an independent prognostic predictor.

目的 研究新型个性化可调式口腔矫治器治疗轻中度阻塞性睡眠呼吸暂停低通气综合征(OSAHS)的疗效及安全性.方法 采用多中心自身对照方法,38例轻中度OSAHS患者佩戴口腔矫治器治疗1个月,记录佩戴前、后呼吸暂停低通气指数(AHI)、最低动脉血氧饱和度(lowest SaO2,LSaO2)、鼾声指数、Epworth嗜睡量表(Epworth sleepiness score,ESS)评分、鼾声视觉模拟量表(visual analogue scale,VAS)评分及口腔矫治器使用情况.结果 37例OSAHS患者完成临床试验,有效率为67.6％ (25/37),AHI、鼾声指数、ESS评分、鼾声VAS评分下降,LSaO2上升,具有统计学意义(P＜0.05).患者主要不良反应为佩戴时轻微疼痛(1/37),佩戴时对言语功能轻微影响(4/37),佩戴时对吞咽功能轻微影响、流口水(3/37).结论 新型个性化可调式口腔矫治器治疗轻中度OSAHS具有较好的疗效及安全性,不良反应少,依从性高.

OBJECTIVES:Inner ear malformations (IEM) with cerebrospinal fluid (CSF) leakage in children is a rare condition, nevertheless, it may lead to meningitis. Early diagnosis and treatment are crucial. The aims of the study were to summarize the clinical characteristic of pediatric CSF leakage secondary to IEM, and to recommend transcanal endoscopic ear surgery (TEES) as an effective surgical technique for the treatment of CSF leakage with IEM in children.METHODS:This was a retrospective study. Thirteen children and fourteen ear surgery were included. Demographics, detail history, laboratory data, Audio test, and imageological examination results were recorded. All the pediatric patients underwent TEES.RESULTS:Most (92.31%) of the children presented with a history of rhinorrhea. 69.23% (9/13) of the children had suffered from meningitis, and the other had presented with respiratory tract infections. The follow-up duration ranged from 0.75 years to 5.29 years. Transcanal endoscopic repair of CSF leakage secondary to IEM was the first surgery with a success rate of 92.86% (13 out of 14 cases). A fistula could be found in the stapes footplate in all pediatric patients.CONCLUSION:Even if there has been no history of meningitis, the diagnosis of CSF leakage in children suffering from unilateral rhinorrhea and recurrent respiratory tract infection is considered. Auditory brainstem response (ABR) and Temporal bone computed tomography (CT) examinations are suggested to identify IEM. The TEES procedure is recommended in our study as the first choice that repairs CSF leakage secondary to IEM.

Objective:To analyses the value of an improved methods of Muller's test, pharyngeal airway pressure monitoring test（PAPMT）, in topodiagnosis of OSA. Method:One hundred and one cases with OSA（AHI≥5 times per hour） and 30 normal adults were included in the study. Under the pressure monitoring, the electronic laryngoscope were stayed at the palatopharyngeal and glossopharyngeum. First, observe the maximum expiratory pressure and the minimum spiratory pressure. And then measure and record changes of pharynx cross-sectional area at palatopharyngeal and glossopharyngeum under the different pressure. At Last, analyses the correlation between changes of Pharynx cross-sectional area with polysomnography（PSG）. Result:①In 101 cases with OSA, the maximal inspiratory pressure of Müller's manerver distribution is between 1 and 8 kPa. ②The changes of pharynx cross-sectional area of OSA at palatopharyngeal and glossopharyngeum is significantly greater than the control group, and there were obvious differences between OSA and the control group. ③In OSA group, the plug rate at palatopharyngea was 96% and the plug rate at glossopharyngeum is 34% at the minimum pressure. There are no cases have pharynx jams at the control group. ④The main cause of the palatopharyngeal obstruction was strictures in left and right（73%）, and the anatomical factors causing obstruction mainly were, thicken of the pharyngeal wall. The main cause of the hypopharyngeal obstruction was strictures in front and back（71%）, and the redundant lymph tissue at tongue base and posterior displacement of the tongue base, and collapse of pharyngeal wall played an important role at tongue-pharyngeal obstruction. ⑤The changes of pharynx cross-sectional area at palatopharyngeal and glossopharyngeum when the pressure is ±4 kPa is greater than when the pressure is ±2 kPa. ⑥When the pressure is ±2 kPa, The changes of pharynx cross-sectional area at palatopharyngeal is greater than at glossopharyngeum. ⑦Diminished pharyngeal apertures and collapsibility were associated with increased rates of apnea and hypopnea index and the suction pressure（P<0.05）. Conclusion:①PAPMT is able to measure and calculate the changes of pharynx cross-sectional area, determine the site of obstruction, and help the treatment. ②The primary site of obstruction is at velopharyngeal in OSA group. ③The changes of pharynx cross-sectional area at palatopharyngeal and glossopharyngeum of patients can reflects the severity of the OSA.

Objective:This study was designed to show the preliminary efficacy and safety of the improved tongue base suspension surgery in severe obstructive sleep apnea(OSA) patients classified as Friedman Ⅱand Friedman Ⅲ. Method:The severe OSA patients diagnosed by PSG as Friedman Ⅱ type and Ⅲ type underwent surgery treatment. The tongue base of the patient was implanted with titanium plate and fixed on the chin of mandible. The UPPP surgery was performed with reference to H-UPPP. After surgery, the patients were followed up, PSG was re-examined and the change of various subjective and objective indicators of rehabilitation and adverse reactions were observed and recorded.Result: One hundred and two patients with severe OSA who were not tolerant or unwilling to use CPAP treatment were treated by the above surgical method. All the patients underwent surgery successfully and generally recovered about 1 month after the surgery without obvious tongue base pain, foreign body sensation or other discomfort. Eating and speaking function were as usual, the wound was healed well, and no serious infection or rejection was observed. The main postoperative adverse reactionwas tension line fracture(3 cases). Sixty-seven patients completed follow-up. At 3 to 6 months after surgery, the AHI, ESS sleepiness score and snore index were lower than those before surgery, while LSaO₂and CT 90% were higher than those before surgery(P<0.01). The AHI before surgery was 60.5± 22.4, and the average AHI after surgery was 27.8± 22.4. The effective rate of the surgery was 71.6% and the success rate was 58.2%. The AHI has dropped by an average of 54.0%, and snore improved by 63.9%. Conclusion: After preliminary clinical observation, the study suggests that the improved tongue base suspension with UPPP has satisfactory curative effect and feasibility for the treatment of severe OSA patients classified as Friedman Ⅱ type and Ⅲ type.