Synthetic MRI and amide proton transfer-weighted MRI for differentiating between benign and malignant sinonasal lesions.

OBJECTIVES: To explore the value of the synthetic MRI (SyMRI), combined with amide proton transfer-weighted (APTw) MRI for quantitative and morphologic assessment of sinonasal lesions, which could provide relative scale for the quantitative assessment of tissue properties. METHODS: A total of 80 patients (31 malignant and 49 benign) with sinonasal lesions, who underwent the SyMRI and APTw examination, were retrospectively analyzed. Quantitative parameters (T1, T2, proton density (PD)) and APT % were obtained through outlining the region of interest (ROI) and comparing the two groups utilizing independent Student t test or a Wilcoxon test. Receiver operating characteristic curve (ROC), Delong test, and logistic regression analysis were performed to assess the diagnostic efficiency of one-parameter and multiparametric models. RESULTS: SyMRI-derived mean T1, T2, and PD were significantly higher and APT % was relatively lower in benign compared to malignant sinonasal lesions (p < 0.05). The ROC analysis showed that the AUCs of the SyMRI-derived quantitative (T1, T2, PD) values and APT % ranged from 0.677 to 0.781 for differential diagnosis between benign and malignant sinonasal lesions. The T2 values showed the best diagnostic performance among all single parameters for differentiating these two masses. The AUCs of combined SyMRI-derived multiple parameters with APT % (AUC = 0.866) were the highest than that of any single parameter, which was significantly improved (p < 0.05). CONCLUSION: The combination of SyMRI and APTw imaging has the potential to reflect intrinsic tissue characteristics useful for differentiating benign from malignant sinonasal lesions. CLINICAL RELEVANCE STATEMENT: Combining synthetic MRI with amide proton transfer-weighted imaging could function as a quantitative and contrast-free approach, significantly enhancing the differentiation of benign and malignant sinonasal lesions and overcoming the limitations associated with the superficial nature of endoscopic nasal sampling. KEY POINTS: • Synthetic MRI and amide proton transfer-weighted MRI could differentiate benign from malignant sinonasal lesions based on quantitative parameters. • The diagnostic efficiency could be significantly improved through synthetic MRI + amide proton transfer-weighted imaging. • The combination of synthetic MRI and amide proton transfer-weighted MRI is a noninvasive method to evaluate sinonasal lesions.

Vocal Cord Leukoplakia Classification Using Siamese Network Under Small Samples of White Light Endoscopy Images.

OBJECTIVE: Accurate vocal cord leukoplakia classification is instructive for clinical diagnosis and surgical treatment. This article introduces a reliable very deep Siamese network for accurate vocal cord leukoplakia classification. STUDY DESIGN: A study of a classification network based on a retrospective database. SETTING: Academic university and hospital. METHODS: The white light image datasets of vocal cord leukoplakia used in this article were classified into 6 classes: normal tissues, inflammatory keratosis, mild dysplasia, moderate dysplasia, severe dysplasia, and squamous cell carcinoma. The classification performance was assessed by comparing it with 6 classical deep learning models, including AlexNet, VGG Net, Google Inception, ResNet, DenseNet, and Vision Transformer. RESULTS: Experiments show the superior classification performance of our proposed network compared to state-of-the-art methods. The overall accuracy is 0.9756. The values of sensitivity and specificity are very high as well. The confusion matrix provides information for the 6-class classification task and demonstrates the superiority of our proposed network. CONCLUSION: Our very deep Siamese network can provide accurate classification results of vocal cord leukoplakia, which facilitates early detection, clinical diagnosis, and surgical treatment. The excellent performance obtained in white light images can reduce the cost for patients, especially those living in developing countries.

ESCO2 promotes hypopharyngeal carcinoma progression in a STAT1-dependent manner.

BACKGROUND: The establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the development of multiple malignancies. However, its role in hypopharyngeal carcinoma (HPC) progression remains uncharacterized. METHODS: This study employed bioinformatics to determine the ESCO2 expression in head and neck squamous cell carcinoma (HNSC) and normal tissues. In vitro cell proliferation, migration, apoptosis, and/or cell cycle distribution assays were used to determine the function of ESCO2 and its relationship with STAT1. Xenograft models were established in nude mice to determine ESCO2 in HPC growth in vivo. Co-immunoprecipitation/mass spectrometry (Co-IP/MS) was conducted to identify the potential ESCO2 binding partners. RESULTS: We found that ESCO2 expression was elevated in HNSC tissues, and ESCO2 depletion suppressed tumor cell migration in vitro and inhibited tumor growth in vitro and in vivo. Co-IP/MS and immunoblotting assays revealed the interaction between ESCO2 and STAT1 in HPC cells. STAT1-overexpression compromised ESCO2-mediated suppressive effects on HPC cell proliferation, viability, and migration. CONCLUSIONS: These findings suggest that ESCO2 is crucial in promoting HPC malignant progression through the STAT1 pathway and provides novel therapeutic targets for HPC treatment.

Neuronal MeCP2 in the dentate gyrus regulates mossy fiber sprouting of mice with temporal lobe epilepsy.

Sprouting of mossy fibers, one of the most consistent findings in tissue from patients with mesial temporal lobe epilepsy, exhibits several uncommon axonal growth features and has been considered a paradigmatic example of circuit plasticity that occurs in the adult brain. Clarifying the mechanisms responsible may provide new insight into epileptogenesis as well as axon misguidance in the central nervous system. Methyl-CpG-binding protein 2 (MeCP2) binds to methylated genomic DNA to regulate a range of physiological functions implicated in neuronal development and adult synaptic plasticity. However, exploring the potential role of MeCP2 in the documented misguidance of axons in the dentate gyrus has not yet been attempted. In this study, a status epilepticus-induced decrease of neuronal MeCP2 was observed in the dentate gyrus (DG). An essential regulatory role of MeCP2 in the development of functional mossy fiber sprouting (MFS) was confirmed through stereotaxic injection of a recombinant adeno-associated virus (AAV) to up- or down-regulate MeCP2 in the dentate neurons. Chromatin immunoprecipitation sequencing (ChIP-seq) was performed to identify the binding profile of native MeCP2 using micro-dissected dentate tissues. In both dentate tissues and HT22 cell lines, we demonstrated that MeCP2 could act as a transcription repressor on miR-682 with the involvement of the DNA methylation mechanism. Further, we found that miR-682 could bind to mRNA of phosphatase and tensin homolog (PTEN) in a sequence specific manner, thus leading to the suppression of PTEN and excessive activation of mTOR. This study therefore presents a novel epigenetic mechanism by identifying MeCP2/miR-682/PTEN/mTOR as an essential signal pathway in regulating the formation of MFS in the temporal lobe epileptic (TLE) mice. SIGNIFICANCE STATEMENT: Understanding the mechanisms that regulate axon guidance is important for a better comprehension of neural disorders. Sprouting of mossy fibers, one of the most consistent findings in patients with mesial temporal lobe epilepsy, has been considered a paradigmatic example of circuit plasticity in the adult brain. Although abnormal regulation of DNA methylation has been observed in both experimental rodents and humans with epilepsy, the potential role of DNA methylation in this well-documented example of sprouting of dentate axon remains elusive. This study demonstrates an essential role of methyl-CpG-binding protein 2 in the formation of mossy fiber sprouting. The underlying signal pathway has been also identified. The data hence provide new insight into epileptogenesis as well as axon misguidance in the central nervous system.

Vocal cord leukoplakia classification using deep learning models in white light and narrow band imaging endoscopy images.

BACKGROUND: Accurate vocal cord leukoplakia classification is critical for the individualized treatment and early detection of laryngeal cancer. Numerous deep learning techniques have been proposed, but it is unclear how to select one to apply in the laryngeal tasks. This article introduces and reliably evaluates existing deep learning models for vocal cord leukoplakia classification. METHODS: We created white light and narrow band imaging (NBI) image datasets of vocal cord leukoplakia which were classified into six classes: normal tissues (NT), inflammatory keratosis (IK), mild dysplasia (MiD), moderate dysplasia (MoD), severe dysplasia (SD), and squamous cell carcinoma (SCC). Vocal cord leukoplakia classification was performed using six classical deep learning models, AlexNet, VGG, Google Inception, ResNet, DenseNet, and Vision Transformer. RESULTS: GoogLeNet (i.e., Google Inception V1), DenseNet-121, and ResNet-152 perform excellent classification. The highest overall accuracy of white light image classification is 0.9583, while the highest overall accuracy of NBI image classification is 0.9478. These three neural networks all provide very high sensitivity, specificity, and precision values. CONCLUSION: GoogLeNet, ResNet, and DenseNet can provide accurate pathological classification of vocal cord leukoplakia. It facilitates early diagnosis, providing judgment on conservative treatment or surgical treatment of different degrees, and reducing the burden on endoscopists.

The relationship of tongue fat content and efficacy of uvulopalatopharyngoplasty in Chinese patients with obstructive sleep apnea.

BACKGROUND: To investigate the relationship between tongue fat content and severity of obstructive sleep apnea (OSA) and its effects on the efficacy of uvulopalatopharyngoplasty (UPPP) in the Chinese group. METHOD: Fifty-two participants concluded to this study were diagnosed as OSA by performing polysomnography (PSG) then they were divided into moderate group and severe group according to apnea hypopnea index (AHI). All of them were also collected a series of data including age, BMI, height, weight, neck circumference, abdominal circumference, magnetic resonance imaging (MRI) of upper airway and the score of Epworth Sleepiness Scale (ESS) on the morning after they completed PSG. The relationship between tongue fat content and severity of OSA as well as the association between tongue fat content in pre-operation and surgical efficacy were analyzed.Participants underwent UPPP and followed up at 3rd month after surgery, and they were divided into two groups according to the surgical efficacy. RESULTS: There were 7 patients in the moderate OSA group and 45 patients in the severe OSA group. The tongue volume was significantly larger in the severe OSA group than that in the moderate OSA group. There was no difference in tongue fat volume and tongue fat rate between the two groups. There was no association among tongue fat content, AHI, obstructive apnea hypopnea index, obstructive apnea index and Epworth sleepiness scale (all P > 0.05), but tongue fat content was related to the lowest oxygen saturation (r=-0.335, P < 0.05). There was no significantly difference in pre-operative tongue fat content in two different surgical efficacy groups. CONCLUSIONS: This study didn't show an association between tongue fat content and the severity of OSA in the Chinese group, but it suggested a negative correlation between tongue fat content and the lowest oxygen saturation (LSaO2). Tongue fat content didn't influence surgical efficacy of UPPP in Chinese OSA patients. TRIAL REGISTRATION: This study didn't report on a clinical trial, it was retrospectively registered.

TP53 gain-of-function mutation modulates the immunosuppressive microenvironment in non-HPV-associated oral squamous cell carcinoma.

BACKGROUND: TP53, the most mutated gene in solid cancers, has a profound impact on most hallmarks of cancer. Somatic TP53 mutations occur in high frequencies in head and neck cancers, including oral squamous cell carcinoma (OSCC). Our study aims to understand the role of TP53 gain-of-function mutation in modulating the tumor immune microenvironment (TIME) in OSCC. METHODS: Short hairpin RNA knockdown of mutant p53R172H in syngeneic oral tumors demonstrated changes in tumor growth between immunocompetent and immunodeficient mice. HTG EdgeSeq targeted messenger RNA sequencing was used to analyze cytokine and immune cell markers in tumors with inactivated mutant p53R172H. Flow cytometry and multiplex immunofluorescence (mIF) confirmed the role of mutant p53R172H in the TIME. The gene expression of patients with OSCC was analyzed by CIBERSORT and mIF was used to validate the immune landscape at the protein level. RESULTS: Mutant p53R172H contributes to a cytokine transcriptome network that inhibits the infiltration of cytotoxic CD8+ T cells and promotes intratumoral recruitment of regulatory T cells and M2 macrophages. Moreover, p53R172H also regulates the spatial distribution of immunocyte populations, and their distribution between central and peripheral intratumoral locations. Interestingly, p53R172H-mutated tumors are infiltrated with CD8+ and CD4+ T cells expressing programmed cell death protein 1, and these tumors responded to immune checkpoint inhibitor and stimulator of interferon gene 1 agonist therapy. CIBERSORT analysis of human OSCC samples revealed associations between immune cell populations and the TP53R175H mutation, which paralleled the findings from our syngeneic mouse tumor model. CONCLUSIONS: These findings demonstrate that syngeneic tumors bearing the TP53R172H gain-of-function mutation modulate the TIME to evade tumor immunity, leading to tumor progression and decreased survival.

Association between obstructive sleep apnea and thyroid function: A 10-year retrospective study.

PURPOSE: To explore whether the obstructive sleep apnea (OSA) has an impact on thyroid function in patients. METHOD: The data of 853 patients were retrospectively collected from the Second Affiliated Hospital of Xi'an Jiaotong University in recent ten years. All the objects were divided into the control group, mild-moderate and severe OSA groups according to the result of polysomnography. RESULTS: In the non-elderly population (age <60), there were significant differences in serum free triiodothyronine (FT3) and total triiodothyronine (TT3) between the mild-moderate and severe OSA groups (all p < 0.05). And there were differences in serum total thyroxine, anti-thyroid peroxidase, and antithyroglobulin between the control and mild-moderate OSA groups (all p < 0.05). Moreover, FT3 was associated with age (OR = 0.98, p < 0.05) and apnea-hypopnea index (OR = 1.01, p < 0.05). The occurrence of thyroid nodules was associated with average transcutaneous oxygen saturation (Mean SaO2) (OR = 0.97, p < 0.05). In the elderly (age ≥60), there was no difference in FT3 and TT3 between the mild-moderate and severe OSA. While the occurrence of thyroid nodules was also associated with Mean SaO2 (OR = 0.90, p < 0.05). CONCLUSION: In the non-elderly population, the progress of OSA may promote the increase in thyroid hormone (especially FT3) levels, while in the elderly population not. In the whole age population, Mean SaO 2 is associated with the occurrence of thyroid nodules. Future research on the relationship between OSA and thyroid function, and age stratification is necessary.

[The application of waterless empirical taste test（WETT®ï¼‰ in 159 Chinese healthy subjects].

Objective:This study examined the influences of age and gender on the taste function of a sizable sample of healthy Chinese subjects using the Waterless Empirical Taste Test（WETT®ï¼‰, and provided scientific evidences for taste evaluation in clinic. Methods:A total of 159 subjects were tested based on strict inclusion and exclusion criteria. The 53 stimuli strips, presented on monomer cellulose pads, were designed to test 5 basic taste functions including sour, sweet, bitter, salty and umami of all subjects. The analysis was computed in SAS 9.4 statistical software. Results:The total taste score of the subjects was 35.00±8.94; the average test administration time was（21.61±7.80） min. The total test scores decreased across age categories（young group: 37.41±8.12, middle-aged group: 34.48±9.04, elderly group: 29.31±8.64）, the correlation coefficient between the total test scores and age was r=-0.335, P<0.05. There were significant differences in sour and bitter scores among different age groups（Psour=0.019, Pbitter<0.001）. Overall, women outperformed men on the total test（[36.53±8.72]vs[32.93±8.87], P=0.012）. There were correlations among individual taste of scores, and the correlation coefficient between umami and total score was the strongest（rumami/total=0.700，P<0.05）. Conclusion:This study demonstrated that a simple self-administered taste test, the WETT®, could be applied to Chinese healthy people. Age and gender-effects are the main factors which affect gustatory function.

Submucosal Clustered Brownish Microvessels Based on NBI Endoscopy: A Characteristic of LPR.

OBJECTIVE: This study aimed to analyze the characteristics of laryngopharyngeal reflux (LPR) by using narrow band imaging (NBI) endoscopy. STUDY DESIGN: A prospective study. SETTING: A large-volume practice with tertiary care providers. METHODS: A total of 67 patients with suspected LPR who underwent 24-hour multichannel intraluminal impedance-pH monitoring were included from June 2020 to March 2022. Manifestations of NBI endoscopy included submucosal clustered brownish microvessels (CBMs), spotted brownish microvessels, and no special microvessels; the latter 2 formed the non-CBM group. The manifestations of all patients and their changes were observed after 8 weeks of proton pump inhibitor and symptomatic treatment for patients with LPR, and symptomatic treatment for patients without LPR. RESULTS: According to the results of 24-hour multichannel intraluminal impedance-pH monitoring, the incidence of submucosal CBMs was significantly higher in patients with LPR (30 cases) than in those without LPR (37 cases, P < .001), particularly in the posterior cricoid area (P < .001). Besides Reflux Finding Score, the incidence of signs such as subglottic edema and vocal fold edema was significantly higher in the CBM group than the non-CBM group (P < .05). Finally, 22 patients with LPR (91.7%) and only 2 patients without LPR (28.6%) underwent a transformation from CBMs to spotted brownish microvessels after continuous medication for 8 weeks in the CBM group (χ2 = 15.916, P < .001), while no significant change was observed in patients with or without LPR in the non-CBM group (P > .05). CONCLUSION: Submucosal CBMs in the posterior cricoid area under NBI endoscopy may be a characteristic of LPR.

Serum neurofilament light reflects cognitive dysfunctions in children with obstructive sleep apnea.

BACKGROUND: In children, obstructive sleep apnea (OSA) can cause cognitive dysfunctions. Amyloid-beta and tau are elevated in OSA. Neurofilament light (NfL) is a marker of neuro-axonal damage, but there are no reports of NfL for OSA. The objective was to investigate the serum levels of NfL and tau in children with or without OSA and explore their relationship with cognitive dysfunctions caused by OSA. METHODS: This retrospective case-control study included children diagnosed with adenoid tonsil hypertrophy from July 2017 to September 2019 at the Second Affiliated Hospital of Xi'an Jiaotong University. Correlations between cognitive scores and tau and NfL were examined. RESULTS: Fifty-six OSA and 49 non-OSA children were included. The serum NfL levels were higher in the OSA group (31.68 (27.29-36.07) pg/ml) than in the non-OSA group (19.13 (17.32-20.95) pg/ml) (P < 0.001). Moreover, NfL was correlated with the course of the disease, apnea-hypopnea index (AHI), obstructive apnea index (OAI), obstructive apnea-hypopnea index (OAHI), average oxygen saturation (SaO2), respiratory arousal index (RAI), and cognitive dysfunctions evaluated by the Chinese Wechsler Intelligence Scale for Children (C-WISC) (all P < 0.05). The area under the receiver operating characteristics curve (AUC) of NfL was 0.816 (95%CI: 0.736-0.897). Multiple regression analysis revealed that NfL was significantly associated with verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ) and full-scale intelligence quotient (FIQ) (P < 0.001, respectively). CONCLUSIONS: Serum NfL levels are associated with the severity of cognitive dysfunctions in children diagnosed with adenoid tonsil hypertrophy and might be a candidate noninvasive, objective marker to identify cognitive dysfunctions in children with OSA.

The effects of Helicobacter pylori eradication therapy on salivary pepsin concentration in patients with laryngopharyngeal reflux.

OBJECTIVE: To investigate the effect of Helicobacter pylori (HP) eradication therapy on salivary pepsin concentration in laryngopharyngeal reflux (LPR) patients with HP infection. MATERIALS AND METHODS: A total of 477 patients with suspected LPR were enrolled from June 2020 to September 2021. Reflux symptom index, reflux finding score, the positive rates and disintegrations per minute values of HP infection detected by 14C urea breath test and salivary pepsin concentrations analyzed using enzyme-linked immunosorbent assay were compared in LPR patients and non-LPR patients with or without HP infection. HP-positive patients were treated with HP eradication therapy while HP-negative patients with PPI therapy. RESULTS: The scores of nagging cough (0.88 vs. 0.50, P = 0.035), erythema or hyperemia (1.93 vs. 1.78, P = 0.035) and vocal fold edema (1.04 vs. 0.85, P = 0.025) were higher in the LPR (+) Hp (+) subgroup than in LPR (+) Hp (-) subgroup. The concentrations of salivary pepsin in the Hp (+) subgroup were higher than in the Hp (-) subgroup either in LPR patients (75.24 ng/ml vs. 61.39 ng/ml, P = 0.005) or the non-LPR patients (78.42 ng/ml vs. 48.96 ng/ml, P = 0.024). Compared to baseline (before treatment), scores of nagging cough (0.35 vs. 0.84, P = 0.019) and erythema or hyperemia (1.50 vs. 1.83, P = 0.039) and the concentrations of salivary pepsin (44.35 ng/ml vs. 74.15 ng/ml, P = 0.017) in LPR patients with HP infection decreased after HP treatment; yet, this was not observed for the LPR patients without HP infection treated with PPI only (P > 0.05). CONCLUSION: HP infection may aggravate the symptoms and signs of LPR patients, partly by increasing their salivary pepsin concentration.

Mutant p53 drives an immune cold tumor immune microenvironment in oral squamous cell carcinoma.

The critical role of the tumor immune microenvironment (TIME) in determining response to immune checkpoint inhibitor (ICI) therapy underscores the importance of understanding cancer cell-intrinsic mechanisms driving immune-excluded ("cold") TIMEs. One such cold tumor is oral cavity squamous cell carcinoma (OSCC), a tobacco-associated cancer with mutations in the TP53 gene which responds poorly to ICI therapy. Because altered TP53 function promotes tumor progression and plays a potential role in TIME modulation, here we developed a syngeneic OSCC models with defined Trp53 (p53) mutations and characterized their TIMEs and degree of ICI responsiveness. We observed that a carcinogen-induced p53 mutation promoted a cold TIME enriched with immunosuppressive M2 macrophages highly resistant to ICI therapy. p53-mutated cold tumors failed to respond to combination ICI treatment; however, the combination of a programmed cell death protein 1 (PD-1) inhibitor and stimulator of interferon genes (STING) agonist restored responsiveness. These syngeneic OSCC models can be used to gain insights into tumor cell-intrinsic drivers of immune resistance and to develop effective immunotherapeutic approaches for OSCC and other ICI-resistant solid tumors.

Predictive Values of Serum IL-33 and sST2 in Endotypes and Postoperative Recurrence of Chronic Rhinosinusitis with Nasal Polyps.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disease with high heterogeneity and postoperative recidivation. The IL-33/ST2 axis is known to be involved in Th2 immune responses. This study is aimed at exploring levels of serum IL-33 and soluble ST2 (sST2) in CRSwNP patients and their potential for predicting CRSwNP endotypes and postoperative recurrence. Methods: The present study recruited 149 CRSwNP patients, 80 of whom were noneosinophilic (neCRSwNP) and 69 eosinophilic (eCRSwNP), as well as 60 healthy controls (HCs). Serum samples were collected from all participants, and sST2 and IL-33 concentrations were measured using ELISA. Multivariate analysis, receiver operating characteristic (ROC) curves, and Kaplan-Meier curves were used to evaluate the value of serum sST2 and IL-33 levels in distinguishing CRSwNP endotypes and predicting postoperative recurrence. Results: The levels of serum sST2 and IL-33 in CRSwNP patients were significantly higher than those in HCs, especially in the eCRSwNP group. Increased sST2 and IL-33 levels were associated with eosinophil counts and percentages in both tissue and blood. Multivariate regression and ROC curve analysis showed that serum sST2 and IL-33 exhibited potential for distinguishing CRSwNP endotypes, and the combination of serum IL-33 and sST2 showed even more predictive power. Finally, 124 CRSwNP patients completed the entire 3-year follow-up. Multivariate analysis and Kaplan-Meier curves showed that serum sST2 and IL-33 levels were associated with recurrence; serum sST2 and IL-33 each exhibited potential for predicting postoperative recurrence, and combining serum sST2 and IL-33 exhibited better accuracy and practicability. Conclusion: Our results suggested that serum sST2 and IL-33 levels were upregulated in CRSwNP patients and related to the degree of mucosal eosinophil infiltration and postoperative recurrence. Serum sST2 and IL-33 might serve as objective biomarkers for distinguishing phenotypes and predicting recurrence in CRSwNP, and their combined use outperformed either marker alone.

[Arousal characteristics in different OSAHS populations].

Objective:This study sought to explore the effect of age on arousal index in patients with OSAHS, and the significance of arousal index among different phenotypes identified through cluster analysis according to clinical symptoms and complications. Methods:A total of 607 adult patients with OSAHS who received polysomnography in the Second Affiliated Hospital of Xi'an Jiaotong University from July 2020 to July 2021 were selected. All patients registered basic human data, symptoms, complaints and complications, completed the Epworth Sleepiness Scale. We explored the distribution of several PSG parameters in different age groups, and included typical symptoms and complications into cluster analysis to explore the parameter differences in patients with different phenotypes. Results:Young patients had the lowest arousal index and arousal frequency in NREM stage, in middle-aged patients, the arousal index was relatively higher, the arousal times during NREM with oxygen desaturation were the highest. Among elderly patients, the wakefulness after sleep onset（WASO） was the longest, the arousal times in REM sleep was the lowest, and the spontaneous arousal times in NREM sleep were the highest（P<0.05）. Among the 3 types according to the cluster analysis, phenotype Ⅰwas characterised by maximally complications, excessive daytime sleepiness and obesity, while memory and attention impairment were obvious in phenotype Ⅱ. Phenotype Ⅲhad minimal complications, relatively better mental state with shorter time-course of snoring and apnea. Phenotype I differed significantly by higher severity, more severe hypoxemia, higher arousal index and longer WASO time（P<0.05）. Conclusion:the arousal index distribution varies among OSAHS patients with different age, and cluster analysis shows that patients with severe symptoms and more complications tend to have higher arousal index.

[The application of NBI endoscopy in finding concealed primary lesions of misdiagnosis of oropharyngeal cancer].

Objective:The aim of this study is to analyze the application value of NBI endoscopy in finding the concealed primary lesions of misdiagnosis of oropharyngeal cancer. Methods:The clinical data of patients with missed oropharyngeal cancer treated in the Department of Otolaryngology Head and neck surgery, the Second Affiliated Hospital of Xi'an Jiaotong University from May 2018 to June 2021, were retrospectively studied, and the missed diagnosis was also analyzed combined with results of NBI endoscopy. Results:In 31 cases of misdiagnosis of oropharyngeal cancer patients, including 25 males and 6 females, there was no significant difference in age, BMI index, course of disease and TNM stage （P> 0.05）, and the pharyngeal or cervical symptoms were the first clinical manifestations of them, containing pharyngeal pain in 17 cases（54.8%） , pharyngeal foreign body sensation in 4 cases（12.9%） and unilateral cervical mass in 10 cases （32.3%）. No laryngoscopy was performed （21 cases） or no primary lesion was found by laryngoscopy （10 cases） at initial diagnosis. Among them, "inflammatory lesions" were given anti-inflammatory treatment with ineffective results or surgical resection was explored for suspicious lesions （17 cases）, or imaging examination （9 cases, including 6 cases with CT and MRI, 3 cases with PET-CT） and cervical lymph node biopsy （5 cases） were carried out for further diagnosis. According to these results, they were given ordinary laryngoscope （2 cases） or NBI endoscopy （29 cases） subsequently, finally they were confirmed as oropharyngeal squamous cellcarcinoma after localized biopsy at the suspicious lesions, indicating that the accuracy of NBI endoscopy in finding the concealed primary lesions of oropharyngeal cancer （93.55%） is significantly higher than that of ordinary electronic laryngoscope （6.45%）（χ²=43.613, P<0.01）. Conclusion:NBI endoscopy has unique advantages in finding oropharyngeal cancer in concealed parts such as tonsil, root of tongue, soft palate and lateral wall of oropharynx, which could reduce misdiagnosis of oropharyngeal cancer.

[Clinical features of diffuse large B-cell lymphoma in head and neck].

Objective:To investigate the clinical features of diffuse large B-cell lymphoma （DLBCL） of head and neck. Methods:A retrospective study was conducted among patients with DLBCL in the Department of otolaryngology and head and neck surgery of the Second Affiliated Hospital of Xi'an Jiaotong University from July 2011 to September 2021. The disease location, clinical manifestations, diagnosis, treatment and prognosis of DLBCL patients in head and neck were analyzed retrospectively. Results:Oropharynx（27 cases, including 25 cases in tonsil）, neck（29 cases）, nasopharynx and nasal cavity （7 cases）were included in 63 cases of DLBCL in head and neck. Pharyngalgia, pharyngeal foreign body sensation and dysphagia were the most common manifestations of oropharyngeal DLBCL, while nasal obstruction, runny nose and hyposmia were the initial manifestations of nasal and nasopharyngeal DLBCL.Under the NBI endoscopy, locally uplifted neoplasm with rough surface mucosa was observed in 34 cases DLBCL patients of oropharynx, nasopharynx and nasal cavity. Among them, 16 cases were covered with yellow-white and patchy pseudomembrane on the surface of the neoplasm, and 5 cases were detected with abnormal new vessels, including 3 cases of tonsils, 1 case of root of tongue, and 1 case of nasopharynx. Painless progressive lymphadenectasis was the common manifestation of DLBCL in head and neck, and the maximum diameter（[21.3±6.7]mm） of neck lymph nodes in the same side of DLBCL was significantly larger than that in the opposite side（[16.0±7.2]mm, P=0.009）. Sixty-three cases of DLBCL in head and neck, including 27 cases of germinal center type（GCB）, 33 cases of nongerminal center type（non-GCB）, and 3 cases of non-specific DLBCL, were confirmed the diagnosis by needle biopsy（33 cases, 52.4%） and surgical resection（30 cases, 47.6%）. The imaging features of DLBCL in head and neck were mostly showed as local soft tissue masses with uniform density and uneven enhancement, and the surrounding structures were often compressed and displaced. All the patients were treated with standard R-CHOP chemotherapy regimens, and overall survival was longer in normal LDH, and overall survival of the patients at low risk of IPI was longer than those at medium-high or high risk of IPI（PLDH=0.011, PIPI=0.022, P<0.05）. Conclusion:DLBCL mainly occurs in oropharynx, especially the unilateral tonsil. When flake yellow-white pseudomembrane adhesion and abnormal neovessels on the surface of the mass are detected under endoscopy, and the ultrasound suggested multiple enlarged lymph nodes in the neck with large iplateral lymph nodes, the possibility of DLBCL should be considered. Surgical resection could be performed for diagnosis if necessary, and early diagnosis would have a better prognosis.

Relationship between serum brain-derived neurotrophic factor and cognitive impairment in children with sleep-disordered breathing.

Background: As an important neuroprotective factor, the brain-derived neurotrophic factor (BDNF) may have a key role in cognitive impairment in children with sleep-disordered breathing (SDB). The main aim of this study was to compare the levels of BDNF and tyrosine kinase receptor B (TrkB) in normal children and those with obstructive sleep apnea (OSA) and primary snoring (PS) and to explore a possible link between BDNF/TrkB, inflammation, and SDB with cognitive impairment in children. Methods: A total of 44 OSA children and 35 PS children who completed polysomnography between October 2017 and October 2019 were enrolled. At the same time, 40 healthy children during the same period were included as a control. Enzyme-linked immunosorbent assay was used to measure serum indices of BDNF, TrkB, interleukin-1beta (IL-1ß), and tumor necrosis factor-alpha (TNF-α). Correlation and pooled analyses were performed between the cognitive scores and four serological indicators. Logistic regression was used to analyze the risk factors for cognitive impairment. Results: Significant differences were found in serum BDNF, TrkB, IL-1ß, and TNF-α between the three groups (all P < 0.01). The serum BDNF and TrkB in the OSA and PS groups were lower than those in the control group, whereas the serum IL-1ß and TNF-α were higher than those in the control group (all P < 0.05). Moreover, among these four indices, the strongest correlation was found between BDNF and the Chinese Wechsler Intelligence Scale (all P < 0.05). Logistic regression analysis revealed a correlation between OSA status, TrkB, and course of mouth breathing and cognitive status. Conclusion: The levels of serum BDNF and TrkB were related to cognitive impairment in children with SDB. Also, BDNF and TrkB could be used as noninvasive and objective candidate markers and predictive indices of cognitive impairment in children with SDB.

[Effect of proton pump inhibitort on salivary pepsin concentration in patients with laryngopharyngeal reflux].

Objective:To investigate the effect of proton pump inhibitor（PPI） treatment on salivary pepsin concentration in laryngopharyngeal reflux（LPR）. Methods:152 patients with suspected LPR complaining non-specific symptoms such as foreign body sensation, dry throat, phlegm and other non-specific symptoms were enrolled， in the Second Affiliated Hospital of Xi'an Jiaotong University from August 2019 to December 2020. According to the scores of reflux symptom index（RSI） and reflux finding score（RFS）, all the patients were divided into LPR （+） group and LPR （-） group, RSI （+） group and RSI （-） group, RFS （+） group and RFS （-） group . Patients in the LPR （+） group were reassessed after 1 month of PPI treatment. Saliva samples were collected from all the patients at initial diagnosis and follow-up diagnosis after treatment. The salivary pepsin concentration was determined by enzyme linked immunosorbent assay （ELISA）. The differences of RSI, RFS scores and salivary pepsin concentrations before and after treatment were compared. Results:The median concentration of salivary pepsin in LPR （+） group was significantly higher than that in LPR （-） group, and （73.01 ng/mL vs 25.66 ng/mL, P<0.01）, the median concentration of salivary pepsin in RFS （+） group were significantly higher than that in RFS （-） group（78.00 ng/mL vs 35.79 ng/mL, P<0.01） Furthermore, the median scores of RSI （11.00 vs 7.00, P<0.05） and RFS （9.00 vs 7.00, P<0.01） of LPR （+） patients notably decreased after PPI treatment for 1 month, and the salivary pepsin median concentration was memorably lower than that before treatment（53.60 ng/mL vs 46.49 ng/mL, P<0.05）. Meanwhile, the scores of symptoms such as pharyngeal paraesthesia, heartburn, chest pain, stomachache, and the scores of signs such as false vocal fold, erythema or congestion, vocal fold edema, posterior commissure hypertrophy and thick endolaryngeal mucus were conspicuously lower after treatment than those before treatment（P<0.05）. Conclusion:After 1 month of PPI treatment, the scores of partial symptoms and signs, and the salivary pepsin concentrations of LPR patients decreased significantly, suggesting that pepsin plays an important role in the pathogenesis of LPR, and pepsin may be closely related to the symptoms and signs such as pharyngeal paraesthesia and vocal fold edema.