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Inhibition of the NLRP3 inflammasome attenuates spiral ganglion neuron degeneration in aminoglycoside-induced hearing loss

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Neural Regeneration Research 2025年第10期20卷 3025-3039页

作者： Jia Fang Zhuangzhuang Li Pengjun Wang Xiaoxu Zhang Song Mao Yini Li Dongzhen Yu Xiaoyan Li Yazhi Xing Haibo Shi Shankai Yin department of Otolaryngology head and neck surgery Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineOtolaryngology Institute of Shanghai Jiao Tong UniversityShanghai Key Laboratory of Sleep Disordered BreathingShanghaiChina department of otorhinolaryngology-head and neck surgery Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial ***,their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct *** addition,the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon *** investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides,we used a C57BL/6J mouse model treated with *** found that the mice exhibited auditory deficits following the acute loss of outer hair *** ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over *** profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response,particularly those related to the NLRP3 *** of the canonical pyroptotic pathway in spiral ganglion neurons was observed,accompanied by infiltration of macrophages and the release of proinflammatory *** intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury *** findings suggest that NLRP3 inflammasome-mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron *** of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.

关键词： degeneration hearing loss macrophages Mcc950 neuroinflammation NLRP3 inflammasome ototoxicity pyroptosis sensorineural hearing loss spiral ganglion neuron

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Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss

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Neural Regeneration Research 2025年第5期20卷 1483-1494页

作者： Xihang Chen Zhifeng Chen Menghua Li Weiwei Guo Shuolong Yuan Liangwei Xu Chang Lin Xi Shi Wei Chen Shiming Yang Senior department of Otolaryngology head and neck surgery Chinese PLA General HospitalChinese PLA Medical SchoolBeijingChina State Key Laboratory of Hearing and Balance Science BeijingChina National Clinical Research Center for Otolaryngologic Diseases BeijingChina Key Laboratory of Hearing Science Ministry of EducationBeijingChina Beijing Key Laboratory of Hearing Impairment Prevention and Treatment BeijingChina department of otorhinolaryngology head and neck surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina department of Otolaryngology head and neck surgery The 940th Hospital of Joint Logistics Support Force of Chinese PLALanzhouGansu ProvinceChina Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikouHainan ProvinceChina academician Workstation of Hainan University School of Pharmaceutical SciencesYazhou BaySanyaHainan ProvinceChina

Noise-induced hearing loss is the primary non-genetic factor contributing to auditory ***,there are currently no effective pharmacological interventions for patients with noise-induced hearing ***,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory *** established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 *** found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with *** noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with *** findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell ***,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy *** treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)*** conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing *** findings suggest that inhibiting lysine-specific demethylase 1 is a

关键词： 4-hydroxynonenal apoptosis autophagy cleaved caspase-3 inflammation NOD-like receptor family pyrin domain-containing 3(NLRP3) noise-induced hearing loss oxidative stress Sestrin2 tranylcypromine

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Adipose-derived mesenchymal stem cells accelerate nerve regeneration and functional recovery in a rat model of recurrent laryngeal nerve injury

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Neural Regeneration Research 2017年第9期12卷 1544-1550页

作者： Yun Li Wen Xu Li-yu Cheng department of otorhinolaryngology-head neck surgery Beijing Tong Ren Hospital Capital Medical University Key Laboratory of otorhinolaryngology-head neck surgery Ministry of Education

Medialization thyroplasty or injection laryngoplasty for unilateral vocal fold paralysis cannot restore mobility of the vocal fold. Recent studies have shown that transplantation of mesenchymal stem cells is effective in the repair of nerve injuries. This study investigated wheth- er adipose-derived stem celt transplantation could repair recurrent laryngeal nerve injury. Rat models of recurrent laryngeal nerve injury were established by crushing with micro forceps. Adipose-derived mesenchymal stem cells （ADSCs; 8 ×105） or differentiated Schwann-like adipose-derived mesenchymal stem cells （dADSCs; 8×105） or extracellular matrix were injected at the site of injury. At 2, 4 and 6 weeks post-surgery, a higher density of myelinated nerve fiber, thicker myelin sheath, improved vocal fold movement, better recovery of nerve conduction capacity and reduced thyroarytenoid muscle atrophy were found in ADSCs and dADSCs groups compared with the extracellu- lar matrix group. The effects were more pronounced in the ADSCs group than in the dADSCs group. These experimental results indicated that ADSCs transplantation could be an early interventional strategy to promote regeneration after recurrent laryngeal nerve injury.

关键词： nerve regeneration mesenchymal stem cell transplantation adipose-derived mesenchymal stem cells recurrent laryngeal nerve larynx nerve injury functional recovery vocal fold cell differentiation neural regeneration

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Epidemiological Features of Allergic Rhinitis in Four Major Cities in Western China

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2011年第4期31卷 433-440页

作者：申迹柯霞洪苏玲曾庆梁传余李同英唐安洲 department of otorhinolaryngology-head and neck surgery The People's Hospital of Changshou department of otorhinolaryngology-head and neck surgery The First Affiliated Hospital of Chongqing Medical University department of Epidemiology and Hygienic Statistics Chongqing Medical University department of otorhinolaryngology-head and neck surgery West China Hospital of Sichuan University department of otorhinolaryngology-head and neck surgery The First Affiliated Hospital of Xinjiang Medical University department of otorhinolaryngology-head and neck surgery The First Affiliated Hospital of Guangxi Medical University

Allergic rhinitis（AR）,with an increasing uptrend of the prevalence in many developed and developing countries,is a global health problem that affects people of all ages and ethnic ***,data on the prevalence of self-reported AR in western China are *** study investigated the epidemiological features of self-reported AR in western *** the cross-sectional,population-based study,a validated questionnaire survey on self-reported AR was carried out in 4 major cities in western China by multistage,stratified and cluster sampling,from January to December *** total prevalence rate was 34.3%,with 32.3%（Chongqing）,34.3%（Chengdu）,37.9%（Urumqi）,30.3%（Nanning）,*** prevalence presented to increase with age before 30 years old while decrease with age after 30 years old,and the highest prevalence was in 19-30 years group in Chongqing,Chengdu and Nanning which significantly showed ＂persistent and moderate-severe＂ type（P0.0001）;In Urumqi,there wasn＇t a significant increasing or decreasing trend of prevalence rate with age but with an ＂intermittent and mild＂predominance（P0.0001）.There were no distinct sexual differences in prevalence rates in the 4 *** morbidity was positively related to monthly average temperature and sunshine（r=0.76645,P=0.0036;r=0.67303,P=0.0165）,but negatively associated with relative humidity（r=-0.64391,P=0.0238） in ***,the monthly morbidity was negatively associate with average temperature,sunshine and precipitation in Nanning（r=-0.81997,P=0.0011;r=-0.60787,P=0.0360;r=-0.59443,P=0.0415）.Self-reported AR is becoming common in western China with a rapid development in recent years,affecting about three persons out of *** climatic factors may have an indirect impact on the prevalence rate through the effects on the local allergens.

关键词： western China epidemiology intermittent allergic rhinitis persistent allergic rhinitis self-reported allergic rhinitis

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Factors contributing to lymph node occult metastasis in supraglottic laryngeal carcinoma cT2-T4 N0M0 and metastasis predictive equation

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Chinese Journal of Cancer Research 2014年第6期26卷 685-691页

作者： Hongzhi Ma Meng Lian Ling Feng Pingdong Li Lizhen Hou Xiaohong Chen Zhigang Huang Jugao Fang department of Otolaryngology-head and neck surgery Beijing Tongren Hospital Capital Medical University Key Laboratory of otorhinolaryngology head and neck surgery Ministry of Education Beijing Institute of Otorhinolaryngology Beijing Key Laboratory of head and neck Molecular Diagnostic Pathology

Objective： To investigate factors that contribute to lymph node metastasis（LNM） from clinical cT2-T4 N0M0（cN0） supraglottic laryngeal carcinoma（SLC）, and to predict the risk of occult metastasis before ***： A total of 121 patients who received surgery were retrospectively analyzed. Relevant factors regarding cervical LNM were analyzed. Multivariate analyses were conducted to predict the region where the metastasis occurred and prognosis. Results： The overall metastatic rate of c N0 SLC was 28.1%. Metastatic rates were 15.4%, 32.5% and 35.7% for T2, T3 and T4, respectively. Metastatic rates for SLC levels II, III and IV were 19.6%, 17.2% and 3.6%, respectively. A regression equation was formulated to predict the probability of metastasis in cN0 SLC as follows： Pn=e（–3.874＋0.749T3＋1.154T4＋1.935P1＋1.750P2）/[1＋e（–3.874＋0.749T3＋1.154T4＋1.935P1＋1.750P2）]. Approximately 0.2% of patients experienced LNM with no recurrence of laryngeal cancer. Comparison of the intergroup survival curves between patients with and without LNM indicated a statistically significant difference（P=0.029）.Conclusions： Cervical lymph node metastatic rates tended to increase in tandem with T stage in patients with LNM in cN0 SLC, and neck dissection is advised for these patients. Moreover, cervical LNM in cN0 SLC showed a sequential pattern and may be predicted.

关键词： Larynx lymph nodes neoplasm metastasis prediction

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Otitis media with effusion in children: Pathophysiology, diagnosis, and treatment.A review

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Journal of Otology 2019年第2期14卷 33-39页

作者： Pauline Vanneste Cyril Page department of otorhinolaryngology and head & neck surgery Amiens University Hospital

Otitis media with effusion(OME)is a frequent paediatric *** condition is often asymptomatic,and so can easily be ***,OME can lead to hearing loss that impairs the child's language and behavioural *** diagnosis is essentially clinical,and is based on otoscopy and(in some cases)*** endoscopy is only indicated in cases of unilateral OME or when obstructive adenoid hypertrophy is *** media with effusion is defined as the observation of middle-ear effusion at consultations three months *** must be evaluated(using an age-appropriate audiometry technique)before and after treatment,so as not to miss another underlying cause of deafness(*** deafness).Craniofacial dysmorphism,respiratory allergy and gastro-oesophageal reflux all favour the development of *** a certain number of medications(antibiotics,corticoids,antihistamines,mucokinetic agents,and nasal decongestants)can be used to treat OME,they are not reliably effective and rarely provide long-term *** benchmark treatment for OME is placement of tympanostomy tubes(TTs)and(in some cases)adjunct *** TTs rapidly normalize hearing and effectively prevent the development of cholesteatoma in the middle *** contrast,TTs do not prevent progression towards tympanic atrophy or a retraction *** enhances the effectiveness of *** children with adenoid hypertrophy,adenoidectomy is indicated before the age of 4 but can be performed later when OME is identified by nasal *** must be followed up until OME has disappeared completely,so that any complications are not missed.

关键词： Otitis media with effusion Tympanostomy tube Ventilation tube Grommet Child

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Effect of RNA interference therapy on the mice eosinophils CCR3 gene and granule protein in the murine model of allergic rhinitis

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Asian Pacific Journal of Tropical Medicine 2014年第3期7卷 226-230页

作者： Xin-Hua Zhu Bing Liao Ke Liu Yue-Hui Liu department of otorhinolaryngology head and neck surgery the Second Affiliated Hospital of Nanchang University department of head and neck surgery the Tumor Hospital of Jiangxi Province

Objective:To observe the clinical manifestations of allergic rhinitis mice and the expression changes of the eosinophils CCR3 and the granule protein rnRNA in the bone marrow,peripheral blood and nasal lavage ***:Twenty-four BALB/c mice were randomly divided into the control *** therapy *** therapy group and the CCR3 siRNA therapy group(n=6).Allergic rhinitis model were sensitized and stimulated by ovalbunfin,and CCR3 siKNA therapy group were administered with CCH3 transnasally before *** levels of the eosinophils *** and EPO in bone marrow,peripheral blood and nasal lavage fluid were detected by ***:Compared to the control group and CCR3 *** therapy group,the nasal mucosa of the PBS therapy group and siRNA therapy group developed *** cells hyperplasia,squamous epithelium metaplasia,epithelium necrosis,lamina propria and submucosa gland hyperplasia,vasodilatation,tissue edema,and the characterized eosinophil ***-PCR indicated that the CCR3 rnRNA,*** and EPC)expression in bone marrow,peripheral blood and nasal lavage fluid of the CCR3 siKNA therapy group was lower than the PBS therapy group and *** therapy group(P<0.05).Conclusions:The RNA interference therapy to CCR3 by local administration pernasal can suppress the process of the development,migration and invasion of the allergic rhinitis eosinophil,thus can reduce the effect of eosinophils and then reduce the inflammation effect of the allergic *** may be a new treatment for respiratory tract allergic inflammation.

关键词： Allergic rhinitis Eosinophil CCR3 RNA interfering

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Evaluation of pure-tone audiometric protocols in vestibular schwannoma screening

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Journal of Otology 2021年第3期16卷 138-143页

作者： Matej Vnencak Elina Huttunen Antti A.Aarnisalo Jussi Jero Katja Liukkonen Saku T.Sinkkonen department of otorhinolaryngology-head and neck surgery Turku University HospitalTurkuFinland head and neck Center Otorhinolaryngology-Head and Neck SurgeryHelsinki University HospitalAnd University of HelsinkiHelsinkiFinland

The objective was to evaluate the pure-tone audiogram-based screening protocols in VS *** retrospectively analyzed presenting symptoms,pure tone audiometry and MRI finding from 246 VS patients and 442 controls were collected to test screening protocols(AAO-HNS,AMCLASS-A/B,Charing Cross,Cueva,DOH,Nashville,Oxford,Rule3000,Schlauch,Seattle,Sunderland)for sensitivity and *** were pooled with data from five other studies,and analysis of sensitivity,specificity and positive likelihood ratio(LR+)for each protocol was *** results show that protocols with significantly higher sensitivity(AMCLASS-A/B,Nashville)show also significantly lowest specificity,and tend to have low association(positive likelihood ratio,LR+)to the *** highest LR+was found for protocols AAO-HNS,Rule3000 and *** conclusions,knowing their properties,screening protocols are simple decision-making tools in VS *** use the advantage of the highest sensitivity,protocols AMCLASS-A+B or Nashville can be of *** more reasonable approach,applying the protocols with high LR+(AAO-HNS,Rule3000,Seattle)may reduce the overall number of MRI scans at expense of only few primarily undiagnosed VS.

关键词： Vestibular schwannoma Asymmetric sensorineural hearing loss Screening protocol

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Inhibitory Effects of 5-Aza-2'-Deoxycytidine and Trichostatin A in Combination with p53-Expressing Adenovirus on Human Laryngocarcinoma Cells

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Chinese Journal of Cancer Research 2012年第3期24卷 232-237页

作者： Ling-yan Jiang Meng Lian Hong Wang Ju-gao Fang Qi Wang Key Laboratory of otorhinolaryngology head and neck surgery(Ministry of Education) Beijing Institute of OtorhinolaryngologyBeijing 100005China department of Otorhmolaryngology head and neck surgery Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China

Objective： To investigate the effects of 5-Aza-2＇-deoxycytidine （5-Aza-Cdr） and trichostatin A （TSA） combined with p53-expressing adenovirus （Ad-p53） on Hep-2 cell line in vivo and in vitro, in order to explore its possibility in biological treatment of laryngocarcinoma. Methods： Effects of 5-Aza-Cdr and TSA in combination with Ad-p53 on Hep-2 cell line in vivo were determined by Cell Counting Kit-8 （CCK-8） assay. The effect of drug combination was calculated by Jin＇s formula. Effects on the cell line in vitro were investigated by establishing the nude mice model. Results： 5-Aza-Cdr and TSA showed inhibitory effects on the proliferation of Hep-2 cells in dose- and time-dependent manner. Ad-p53 can inhibit the growth of Hep-2 cells in vivo and in vitro. However, the combination of epigenetic reagents （5-Aza-Cdr/TSA） and Ad-p53 was less effective than individual use of Ad-p53. 5-Aza-Cdr and Ad-p53 inhibited the growth of transplanted tumors and reduced the volume of tumors, and the tumor volume of Ad-p53 group was significantly smaller than that of the control group （P0.05）. Conclusion： Both epigenetic reagents （5-Aza-Cdr/TSA） and Ad-p53 can suppress cell proliferation on Hep-2 in vivo and in vitro and there may be some antagonistic mechanism between Ad-p53 and epigenetic reagents （5-Aza-Cdr/ TSA）.

关键词： 5-Aza-'-deoxycytidine trichostatin A p-expressing adenovirus Hep-2cell line

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Relapsing polychondritis causing breathlessness: Two case reports

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World Journal of Clinical Cases 2022年第23期10卷 8360-8366页

作者： Song-Yu Zhai Yu-Hao Zhang Ru-Yan Guo Jie-Wen Hao Shu-Xin Wen department of otorhinolaryngology head and neck surgery Xi’an Fourth HospitalXi’an 710004Shaanxi ProvinceChina department of otorhinolaryngology head and neck surgery Shanxi Bethune HospitalTaiyuan 030000Shanxi ProvinceChina department of otorhinolaryngology head and neck surgery The First People's Hospital of NanyangNanyang 473000Henan ProvinceChina department of otorhinolaryngology head and neck surgery The Third Clinical College of Shanxi Medical UniversityTaiyuan 030000Shanxi ProvinceChina

BACKGROUND Relapsing polychondritis is a rare multisystem autoimmune disease that mainly involves systemic cartilage and proteoglycan-rich *** the larynx and trachea are involved,the patient’s condition deteriorates *** relapsing polychondritis becomes more advanced,the airways collapse and treatment is difficult,rendering a poor ***,the diagnosis method,treatment strategy and prognosis of relapsing polychondritis with larynx and trachea involvement need to be elucidated to improve clinicians’awareness of the *** SUMMARY A man and a woman were admitted because of *** polychondritis was diagnosed after a series of accessory *** were both treated with glucocorticoids and immunosuppressants,and underwent tracheotomy as their breathing difficulties could not be relieved by the *** The two cases highlight the importance of the timely diagnosis,full evaluation and initiating individualized treatment of relapsing polychondritis with larynx and trachea ***,bronchoscopy and pathological examination are helpful in diagnosis of this disease.

关键词： Relapsing polychondritis Larynx Trachea Case report

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