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The positive feedback loop of activated regulatory T cells (aTregs) and M2 macrophages (M2) play a vital role in promoting the tumor immunosuppressive microenvironment of head and neck squamous cell carcinoma (HNSCC). However, the key factors regulating the positive feedback loop remain unclear. Herein, we investigated the effect of PD-L1 carried on exosomes derived from tumor cells (TEXs) on the aTreg-M2 positive feedback loop, as well as their role in mediating immunosuppression. In our study, TEXs with or without PD-L1 (TEX-PD-L1 or TEX-PD-L1 KO ) were treated with CD4 + CD25 - T cells and M0 macrophages, and the effect on the differentiation of aTregs, M2 and the aTreg-M2 positive feedback loop was assessed. TEXs carried more PD-L1 than tumor cells and not only promoted the differentiation of aTregs and M2, but also, most importantly, enhanced the positive feedback loop of aTreg-M2, which inhibited the proliferation of CD4 + CD25 - T cells and in turn led to tumor immune escape. Moreover, in vivo study showed that TEX-PD-L1 KO could inhibit tumor growth and significantly improve the antitumor efficacy in both the peripheral and tumor microenvironments. Collectively this study revealed the role and mechanism of TEX-PD-L1 in negative immune regulation, and targeting TEX-PD-L1 may be a new idea and strategy for immunotherapy of HNSCC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: This article aims to propose a new surgical method for the treatment of pyriform fistula, especially for the complex pyriform fistula., Methods: A total of 36 patients with pyriform fistula underwent the procedure between August 2017 to October 2020. Surgery was performed by the senior authors using the same technique at the same clinical center for all patients. The median follow-up time was 33 months. Meantime, we collected information on patients with pyriform fistula using traditional surgical methods in our hospital from April 2015 to November 2018 for comparison., Results: The surgery was successfully completed in 36 patients. In all, 32 patients had a history of multiple incisions and drainage, 16 patients had a history of surgical resections, and two patients had a history of cauterization of the internal fistula. Compared with traditional surgical methods, our new surgical method greatly shortens the length of the surgical incision (4.3 vs. 5.5, p  < 0.0001), reduces the operation time (8.1 vs. 27.1, p < 0.0001), and reduces the blood loss (103.2 vs. 196.8, p  < 0.0001). None of the 36 patients in this study had complications such as pharyngeal fistula, recurrent laryngeal nerve paralysis, or hypothyroidism. The mean follow-up duration after the excision of the lesion was 34.1 months. To date, no patients have relapsed., Conclusion: Our experience showed that this surgical technique could be used to completely remove the fistula, and it was easier to perform than the conventional strategies. These treatment options result in less trauma and reliable results, especially for complex pyriform fistulas., Level of Evidence: IV., Competing Interests: All authors declare that there is no conflict of interest associated with this study., (© 2022 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Purpose: Basaloid squamous cell carcinoma (BSCC) is a rare aggressive variant of squamous cell carcinoma (SCC) with a poor prognosis. No large series of exclusively hypopharyngeal BSCC patients have been previously reported. Therefore, this retrospective population-based study aims to explain the patient demographics, clinicopathologic characteristics, incidence, and survival outcomes of hypopharyngeal BSCC and how it relates to conventional-type SCC., Methods: The National Cancer Institute's Surveillance, Epidemiology, and End Results database registry was queried for patients diagnosed with hypopharyngeal BSCC and conventional-type SCC between 2001 and 2016., Results: The incidence of hypopharyngeal BSCC from 2001 to 2016 was 0.0161 per 100,000 individuals. The BSCC group comprised 213 patients, and the SCC group 7958 patients. The majority of BSCCs were considered high grade (Grade III/IV, 89.58%). Most BSCC patients were diagnosed at an advanced stage (American Joint Committee on Cancer [AJCC] stage IV, 65.38%). The 1-, 5-, and 10-year disease-specific survival (DSS) rates for hypopharyngeal BSCC were 84.10%, 57.40%, and 46.20%, respectively. Multivariate analysis, after adjustment for sex, age, race, tumor location, grade, and AJCC stage, showed that patients with BSCC had significantly better DSS than those with conventional-type SCC. Surgery with radiation contributed to a favorable DSS for BSCC patients in comparison with other treatments., Conclusion: This analysis of the largest hypopharyngeal BSCC series indicates a better prognosis for this pathologic type compared with conventional-type hypopharyngeal SCC. Multimodality treatment with surgery and radiation may result in a favorable prognosis for hypopharyngeal BSCC patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The complex contaminants in reclaimed water sources and delayed feedback of microbial detection have brought tremendous challenges to disinfection process control. The identification of sensitive and online surrogates for indicating microbial inactivation efficacy is vital to evaluate and optimize the disinfection technologies and processes. This study analyzes the inactivation of microbial indicators during ozone disinfection at a pilot-scale study over 5 months. It is identified that total fluorescence (TF) intensity, ultraviolet absorbance at 254 nm (UV 254 ) and intracellular adenosine triphosphate (cATP) concentration can act as surrogates in predicting microbial inactivation by ozone. Particularly, the empirical linear correlations for log removal values (LRV) of TF, UV 254 and cATP concentration are developed for the inactivation of four widely applied microbial indicators, namely the total coliforms, fecal coliforms, Escherichia coli (E. coli) and heterotrophic plate count (HPC) (R 2 = 0.86-0.96). Validation analyses are further conducted to verify the robustness and effectiveness of empirical models. Notably, TF is considered as the most efficient surrogate due to its high sensitivity, accuracy and reliability, whereas cATP concentration is an efficient supplement to directly reflect total microbial counts. The study is important to provide a rapid and reliable approach for ozone disinfection efficiency evaluation and prediction., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Chirp auditory steady-state response (ASSR) can be used to assess frequency-specific hearing thresholds. However, its reliability has not been confirmed yet. The purpose of this proposed study is to analyze the agreement of thresholds measured by chirp-ASSR and pure tone audiometry (PTA) to investigate the value of chirp-ASSR in hearing threshold evaluation., Methods: Participants with normal hearing (age: 18-66, 108 ears) and patients with sensorineural hearing loss (age: 22-82, 75 ears) were tested using PTA and chirp-ASSR at 0.5, 1, 2, and 4 kHz, respectively. Intraclass correlation coefficient (ICC) and Bland-Altman plot were introduced to analyze the agreement between the 2 methods., Results: One-hundred eight participants underwent both chirp-ASSR and PTA to estimate their thresholds. The ICCs yielded by these 2 methods are 0.757, 0.893, 0.883, and 0.921 (p < 0.001) at 0.5, 1, 2, and 4 kHz carrier frequency, respectively. However, there is a significant difference between the 2 methods at 2 kHz: the mean value of the ASSR thresholds is 5.27 dB HL higher than the value of PTA thresholds. Additionally, the 95% limits of agreement range from -27.48 to 26.66 dB HL at 0.5 kHz, from -18.19 to 17.87 dB HL at 1 kHz, from -12.01 to 22.55 dB HL at 2 kHz, and from -21.29 to 19.17 dB HL at 4 kHz, which are large enough to affect clinical decision-making., Conclusion: In this study, we have confirmed good to excellent correlation between chirp-ASSR and PTA in threshold estimation for adults with and without hearing loss. The degree of correlations is higher for participants with hearing loss and for measurements at high frequencies. However, significant systematic difference and large limits of agreement between the 2 methods have been found. These findings show that chirp-ASSR can be treated as a supplementary method to PTA when evaluating the hearing level, but the 2 methods are not interchangeable due to their systematic difference and large limits of agreement., (© 2021 S. Karger AG, Basel.)

The 5-year survival rate of laryngeal cancer continues to decline, and the laryngeal particularity of the anatomy adversely affects the patient's quality of life. Emerging evidence suggests that long noncoding RNAs (lncRNAs) are closely correlated to key steps in the malignant progression of cancer cells. In this study, we report the role of lncRNA SBF2-AS1/miR-302b-3p/TGFBR2 interactions in the metastasis of laryngeal squamous cell carcinoma (LSCC). We verified that SBF2-AS1 was significantly downregulated in LSCC tissues and cell lines using qRT-PCR analysis. Its low expression was correlated to lymph node metastasis and an advanced clinical stage. More importantly, LSCC patients with low expression of SBF2-AS1 tended to have a poor prognosis. Based on this, we performed gain-of-function and loss-of-function experiments in LSCC cell lines. The results confirmed that knocking down SBF2-AS1 can promote the metastasis of LSCC cells and enhance epithelial-mesenchymal transition phenotype, while the upregulation of SBF2-AS1 expression resulted in the opposite. Our in vivo model verified that SBF2-AS1 overexpression could inhibit LSCC cell metastasis. Subsequent mechanistic studies revealed that SBF2-AS1 acted as a competing endogenous RNA that upregulated the expression of TGFBR2 by endogenous sponging for miR-302b-3p in LSCC cell lines. Moreover, miR-302b-3p overexpression reversed the inhibitory effects on LSCC metastasis induced by upregulation of SBF2-AS1 expression, and inhibition of TGFBR2 expression reversed the effect of SBF2-AS1 on metastasis. Our study proposes SBF2-AS1 as a biomarker to predict the prognosis of LSCC patients and a novel potential therapeutic target., (© 2021 Wiley Periodicals LLC.)

Objective: We aimed to quantitatively evaluate the degree of endolymphatic hydrops and its correlation with the clinical features of Meniere's disease., Methods: We retrospectively collected data from patients with Meniere's disease who underwent gadolinium-enhanced magnetic resonance imaging (MRI) at our department from January 2018 to December 2019. Mimics software was used to perform three-dimensional modelling of the labyrinth, and volume information was obtained to calculate the endolymphatic hydrops index (EHI). A correlation analysis was conducted with data from pure tone audiometry, electrocochleography (EchoG), vestibular myogenic-evoked potential (VEMP) testing, caloric testing and video head impulse testing (vHIT). A two-dimensional method was also employed to calculate the hydrops ratio (HR) of cochlea and vestibule. The test-retest reliability of EHI/HR from different operators was evaluated., Results: A total of 23 affected ears were examined, and the EHI was significantly correlated with Meniere's disease stage, low-frequency hearing threshold, EchoG summating potential/action potential ratio (-SP/AP) and VEMP binaural asymmetry ratio, but no significant correlation was observed between EHI and the caloric test or vHIT. The Intraclass correlation coefficient (ICC) of EHI data calculated by two otologists was 0.946 (p < .001). And the ICC of cochlea and vestibule HR were 0.844 and 0.832 (p < .001)., Conclusion: Mimics software can be used to quantitatively evaluate the degree of endolymphatic hydrops and have shown higher test-retest reliability than traditional two-dimensional evaluation method. Endolymphatic hydrops correlates with clinical data, such as Meniere's disease stage, low-frequency hearing threshold, EchoG and VEMP asymmetry ratio., (© 2021 John Wiley & Sons Ltd.)

Regulatory T cells (Tregs) are immunosuppressive cells involved in antitumor immunity. However, the regulation of Treg generation by inflammation in the tumor microenvironment has not been carefully investigated. Here, we demonstrated that IL-21-polarized inflammation was enriched in the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC) and that IL-21 could promote PD-L1-induced Treg generation in a PD-1-dependent manner. Moreover, generated Tregs showed a greater ability to suppress the proliferation of tumor-associated antigen (TAA)-specific T cells than naturally occurring Tregs. Importantly, an anti-PD-1 antibody could inhibit only Treg expansion induced by clinical tumor explants with high expression of IL-21/PD-L1. In addition, neutralizing IL-21 could enhance the anti-PD-1 antibody-mediated inhibitory effect on Treg expansion. Furthermore, simultaneous high expression of IL-21 and PD-L1 was associated with more Treg infiltrates and predicted reduced overall and disease-free survival in patients with HNSCC. These findings indicate that IL-21 in the tumor microenvironment may promote PD-L1-induced, Treg-mediated immune escape in a PD-1-dependent manner and that an IL-21 neutralization strategy may enhance PD-1 blockade-based antitumor immunotherapy by targeting Treg-mediated immune evasion in patients with high expression of IL-21 and PD-L1., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhao, Zhang, Lei, Wei, Ma, Wen, Wei, Fan, Xu, Chen, Lyu, Lin, Wen and Sun.)

Head and neck squamous cell carcinoma (HNSCC), the most frequent subtype of head and neck cancer, continues to have a poor prognosis with no improvement. The TNM stage is not satisfactory for individualized prognostic assessment and it does not predict response to therapy. In the present study, we downloaded the gene expression profiles from TCGA database to establish a training set and GEO database for a validation set. In the training set, we developed an 10 immune-related genes signature which had superior predictive value compared with TNM stage. A nomogram including clinical characteristics was also constructed for accurate prediction. Furthermore, it was determined that our prognostic signature might act as an independent factor for predicting the survival of HNSCC patients. As for the immune microenvironment, our results showed higher immune checkpoint expression (CLTA-4 and PD-1) in low-risk group which might reflect a positive immunotherapy response. Thus, our signature not only provided a promising biomarker for survival prediction, but might be evaluated as an indicator for personalized immunotherapy in patients with HNSCC.

Background: The survival benefit of clinically negative cervical lymph nodes (cN0) in patients with T1-2 supraglottic cancer (SC) remains unclear. This study aimed to comprehensively evaluate the prognostic value of lymph node dissection (LND) in patients with T1-2, cN0 SC., Methods: We included 1036 confirmed T1-2, cN0 SC patients with clinicopathological characteristics between 2004 and 2015, based on the Surveillance, Epidemiology, and End Results program (SEER) database. The association between LND and overall survival (OS) was investigated by the Kaplan-Meier method., Results: Before propensity score matching (PSM), patients selected for LND had better OS, compared to patients did not receive LND (5-year OS: 62.6% vs 51.2%, respectively; p = 0.011). After PSM, the LND group also present significant improvement in prognosis (5-year OS: 64.3% vs 51.7%, respectively; p < 0.01)., Conclusions: LND was significantly associated with a more favorable prognosis compared with non-LND in patients with T1-2, cN0 SC., (© 2020 Wiley Periodicals LLC.)

Controversial roles of interleukin-33 (IL-33) have been reported in melanoma from animal studies. We aimed to investigate the role of IL-33 in human cutaneous melanoma. RNA-seq data of 471 cases of cutaneous melanoma were retrieved from The Cancer Genome Atlas. The tumor microenvironment (TME) was deconstructed by the xCell algorithm using RNA-seq data. We evaluated the prognostic value of IL-33 and the relationship between IL-33 and immune components in TME. We also inferred the potential cellular sources of IL-33. All the analyses were conducted separately in three sub-cohorts, which are based on the biopsy sites of samples: primary melanoma; lymph node (LN) metastases; other metastases, including metastases to skin/soft tissue, or visceral sites. In the two metastasis sub-cohorts, IL-33 is associated with better prognosis and more active immune responses in the tumor. However, IL-33 is not a prognostic factor in the primary melanoma sub-cohort. Furthermore, we found that IL-33 is mainly derived from stromal cells in the metastasis sub-cohorts, and from epithelial cells/keratinocytes in the primary melanoma sub-cohort. These findings provide evidence for the context-specific anti-tumor effects of IL-33 in melanoma. And the distinct effects of IL-33 may be determined by the cellular sources of IL-33.

Background: Standardized training allows more physicians to master otoendoscopic surgery. However, the lecture-based learning (LBL) applied in otoendoscopy teaching may not be conducive to training students in clinical thinking and surgical ability. It is necessary to explore innovative methods for otoendoscopy teaching. This study aimed to determine the effect of a step-by-step (SBS) method combined with case-based learning (CBL) in otoendoscopy teaching., Methods: Fifty-nine physicians who participated in otoendoscopy training were selected as the study subjects and randomly divided into two groups (A and B). Group A underwent training with the SBS & CBL method, while Group B underwent training with the LBL & CBL method. The effects of these two methods for otoendoscopy training were compared by evaluation of professional skills and questionnaires before and after the training., Results: Proficiency in otoendoscopic anatomy and grades for both professional knowledge and otoendoscopic skills were significantly higher in Group A than in Group B(P < 0.05). In terms of learning interest, surgical ability, acting capacity during surgery, reducing surgical complications, and satisfaction with learning experience, all responses from Group A were better than those from Group B(P < 0.05)., Conclusions: The SBS & CBL method may help to improve ability in otoendoscopic surgery and clinical thinking and appears suitable for endoscopy teaching.

Background: The purpose of this study was to develop an effective method of reducing metal artifacts in cochlear implant (CI) electrodes., Methods: The temporal bones of 30 patients (34 ears) after CI were examined with 320-detector row computed tomography, which was evaluated by two senior radiologists using a double-blind method. Noise, artifact index, signal-to-noise ratio, and the subjective image quality score were compared before versus after using single-energy metal artifact reduction (SEMAR). The electrode position, single electrode visibility, and electrode count were evaluated using SEMAR combined with either multi-planar reconstruction (MPR) or maximum intensity projection., Results: The two radiologists' measurements had good consistency. SEMAR significantly reduced the image noise and artifacts index and significantly improved the signal-to-noise ratio and subjective image quality score (P < 0.01). The combination of SEMAR with MPR was conducive to accurate assessment of electrode position and single-electrode visibility. The combination of SEMAR with MIP facilitated accurate and intuitive matching of the assessed electrode count with the number of electrodes implanted during the operation (P = 0.062)., Conclusion: SEMAR significantly reduces metal artifacts generated by CI electrodes and improves the quality of computed tomography images. The combination of SEMAR with MPR and maximum intensity projection is beneficial for evaluating the position and number of CI electrodes.

Background: The purpose of this study was to develop an effective management algorithm for lesions of third or fourth branchial sinuses., Study Design: Case series with chart review., Methods: Data from patients who were identified as having third or fourth branchial pouch sinus lesions in a single institution between January 2014 and December 2018 were retrospectively collected., Results: All 67 patients underwent fistulectomy. First, we classified the patients into five types based on their anatomic features. Then, we considered four optimized surgical methods and adopted the appropriate method with full consideration of the patient's clinical characteristics. The great majority of cases occurred on the left side of the neck (68.7%) and most commonly presented as either a recurrent low-neck abscess or cutaneous discharging fistula with neck infection. Effective preoperative examination included administering contrast agent prior to a computed tomography (CT) scan and in-office laryngoscopy during the quiescent period of inflammation. Ultrasound was also very helpful in determining the presence of thyroiditis. The mean follow-up duration after excision of the lesion was 25.8 months. To date, only 1 (1.5%) recurrence and no obvious complications have been observed., Conclusion: Refining fistula subtypes and adopting corresponding treatment measures can reduce the recurrence rate and improve curative effects. We propose and advocate this treatment algorithm for all third and fourth branchial pouch lesions.