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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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Acquired sensorineural hearing loss,oxidative stress,and microRNAs

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Neural Regeneration Research 2025年第9期20卷 2513-2519页

作者： Desmond A.Nunez Ru C.Guo Division of Otolaryngology–head&neck Surgery Department of SurgeryFaculty of MedicineThe University of British ColumbiaVancouverBCCanada Division of Otolaryngology–head&neck Surgery Gordon&Leslie Diamond Health Care CentreVancouver General HospitalVancouverBCCanada Faculty of Medicine–The University of British Columbia VancouverBCCanada

Hearing loss is the third leading cause of human ***-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health ***-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing *** etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental *** stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing *** non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic *** hair cell death is a central histopathological finding in sensorineural hearing *** these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing *** EMBASE,Ovid MEDLINE,Web of Science Core Collection,and *** databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical *** red clinical trials known to the senior author we re also assessed.A total of 222studies were thus *** excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text *** resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative *** miR-34a and miR-29b levels increase with age in *** miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P GC-1α),SIRT

关键词： hearing loss hypoxia microRNAs oxidative stress sensorineural

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Death caused by head and neck Osteosarcoma:A Retrospective Study from a Single institute

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肿瘤预防与治疗 2018年第6期31卷 386-394页

作者： Chen Xiaofang Chen Yiming Bian Xiaohe 季彤 Department of Otolaryngology Second Affiliated Hospital of Fujian Medical University Department of Oral and Maxillofacial-head and neck Oncology Ninth People's HospitalSchool of MedicineShanghai Key Laboratory of Stomatology & Shanghai Research Institute of StomatologyNational Clinical Research Center of StomatologyShanghai Jiao Tong University 上海交通大学医学院附属第九人民医院

Objective: To investigate factors that benefit patients with head and neck osteosarcoma( HNOS) before death. Methods: Patients admitted in our department from 2007 to 2015 who died during follow-up after surgery for HNOS were selected. Information concerning demographics,disease,treatment and follow-up were collected and analyzed. Results: A total of 77 patients died at a median age of 42 years old,of whom 33 were male and 44 female. Thirty-nine tumors were identified in the maxilla and skull base region while 38 in the mandible. Positive surgical margins were observed in 7 cases. Twenty patients received adjuvant chemotherapy,and 36 received postoperative radiotherapy. Local recurrence,as an initial cause of death,occurred in 25 cases,whilst metastasis occurred in the rest. Conclusion: Patients with HNOS benefit from negative surgical margins and adjuvant chemotherapy before death. Patients above 30 years old have longer disease-free survival,and patients with tumors of low pathological grade have longer overall survival. Tumor size and postoperative radiotherapy are negative prognostic factors. Frequent follow-up should be conducted for at least 48 postoperative months.

关键词： head and neck osteosarcoma Cancer specific death Local recurrence Metastases

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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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Primary chordoma of the nose

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Chinese Medical Journal 2003年第1期116卷 154-156页

作者：牟忠林刘兆华 Department of Otolaryngology-head and neck Surgery

Chordoma as a rare malignant tumor arising from remnants of the notochord, accounts for 4% of malignant bone tumors. It occurs twice as frequently in men compared with women and is uncommon in individuals less than 40 years of age.1-3 Topographic distribution is spheno-occipital (35% to 44%), vertebral (15%), and sacrococcygeal (42% to 50%).4 Unusual locations include the mandible and the maxilla, and lesions in these locations have been called ectopic or dental chordomas. Some chordomas with nasal and paranasal presentations have been reported, but primary chordoma of the nose occurs rarely. To our knowlege only two cases have been reported so far according to the literature.4,5 In this paper, we present primary chordoma of the nose, its characteristics and our experiences with it.

关键词： Aged Chordoma Humans Immunohistochemistry Male Nose Neoplasms

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Clinical applications of free medial tibial flap with posterior tibial artery for head and neck reconstruction after tumor resection

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Chinese Journal of Cancer Research 2017年第3期29卷 231-236页

作者： Qi Zhong Jugao Fang Zhigang Huang Xiaohong Chen Lizhen Hou Yang Zhang Pingdong Li Hongzhi Ma Hongbo Xu Department of Otolaryngology head and neck Surgery Beijing Tongren Hospital Capital Medical University Beijing institute of Otolaryngology Key Laboratory of Otolaryngology head and neck Surgery (Capital Medical University) Ministry of Education

Tumor resection causes damage in the head and neck which creates problems in swallowing, chewing, articulation, and vision, all of which seriously affect patients' quality of life. In this work, we evaluated the application of a free medial tibial flap in reconstruction of head and neck defects after tumor resection. We discussed the anatomy, surgical technique, and the advantages and disadvantages of the flap. We found several benefits for the flap, such as, it is especially effective for the defects that require thin-layer epithelium to cover or the separated soft tissue defect; a two-team approach can be used because the donor site is far away from the head and neck; and the flap is easy to integrate because of the subcutaneous fat layer of the free medial tibial flap is thin and the flap is soft. Thus, the medial tibial flap could replace the forearm flap for certain applications.

关键词： head and neck free flap posterior tibial artery reconstruction

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Comparison of human nasal epithelial cells grown as explant outgrowth cultures or dissociated tissue cultures in vitro

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Frontiers of Medicine 2013年第4期7卷 486-491页

作者： Jian Jiao Na Meng Hong Wang Luo Zhang Department of Otolaryngology Head and Neck SurgeryBeijing Tongren HospitalCapital Medical UniversityBeijing 100005ChinaKey Laboratory of OtolaryngologyHead and Neck Surgery(Ministry of Education)Beijing Institute of OtolaryngologyBeijing 100005China

The purpose of this study was to compare cell growth characteristics,ciliated cell differentiation,and function of human nasal epithelial cells established as explant outgrowth cultures or dissociated tissue *** nasal mucosa of the uncinate process was obtained by endoscopy and epithelial cell cultures were established by explant outgrowth or dissociated tissue culture *** cell growth characteristics were observed by inverted phase contrast *** cell differentiation was detected byβ-tubulin IV and ZO-1 *** and ATP-stimulated ciliary beat frequency(CBF)was measured using a high-speed digital microscopic imaging *** the explant and dissociated tissue cultures established as monolayers with tight junctions and differentiated cell composition,with both types of cultures comprising ciliated and non-ciliated epithelial *** were also frequently found in explant cultures but rarely seen in dissociated tissue *** both culture systems,the highest ciliated cell density appeared at 7th–10th culture day and declined with time,with the lifespan of ciliated cells ranging from 14 to 21 ***,10%of the cells in explant cultures and 20%of the cells in the dissociated tissue cultures were *** two cultures demonstrated similar ciliary beat frequency values at baseline(7.78±1.99 Hz and 7.91±2.52 Hz,respectively)and reacted equivalently following stimulation with 100μM *** results of this study indicate that both the explant outgrowth and dissociated tissue culture techniques are suitable for growing well-differentiated nasal ciliated and non-ciliated cells,which have growth characteristics and ciliary activity similar to those of nasal epithelial cells in vivo.

关键词： ciliated cells ciliary beat frequency dissociated tissue culture explant culture nasal epithelial cells

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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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Effects of Kampo medicine hangebyakujutsutemmato on persistent postural-perceptual dizziness:A retrospective pilot study

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World Journal of Clinical Cases 2022年第20期10卷 6811-6824页

作者： Toru Miwa Shin-ichi Kanemaru Department of Otolaryngology-head and neck Surgery Osaka Metropolitan UniversityOsaka 5458585Japan Department of Otolaryngology-head and neck Surgery Tazuke Kofukai Medical Research InstituteKitano HospitalOsaka 5308480Japan Department of Otolaryngology-head and neck Surgery Kyoto UniversityKyoto 7507501Japan

BACKGROUND Persistent postural-perceptual dizziness(PPPD)is a functional disorder,typically preceded by acute vestibular *** is characterized by a shift in processing spatial orientation information,to favor visual over vestibular and somatosensory inputs,and a failure of higher cortical *** date,no therapies for PPPD have been *** medicine hangebyakujutsutemmato(HBT)has been reported to alleviate disturbances of *** hypothesized that HBT would be a beneficial treatment for *** To examine the efficacy of HBT for the treatment of *** Patients with PPPD were enrolled and divided into two groups:The HBT group(n=24)and the non-HBT group(n=14).The participants completed questionnaire surveys[Niigata PPPD questionnaire(NPQ),dizziness handicap inventory,hospital anxiety and depression scale(HADS),orthostatic dysregulation questionnaire,pittsburg sleep quality index(PSQI),and motion sickness scores]before and after HBT ***,to identify HBT responders,multivariate regression analysis was performed using the results of the ques-tionnaire surveys and equilibrium tests;including stabilometry,and caloric,vestibular evoked myogenic response,and head-up tilt *** Thirty-eight outpatients were included in this study,of which 14 patients(3 men,11 women;mean age,63.5±15.9 years)received treatment without HBT,and 24(1 man,23 women;mean age,58.2±18.7 years)received combination treatment with *** HBT treatment,NPQ scores decreased significantly(baseline 40.1±10.0 vs 2 mo 24.6±17.7,Phead-up tilt tests(P<0.001),HADS(P=0.003),and PSQI(P=0.01)were associated with HBT responsiveness in PPPD *** HBT may be an effective adjunct therapy fo

关键词： Hangebyakujutsutemmato Kampo medicine Persistent postural-perceptual dizziness Niigata persistent postural-perceptual dizziness questionnaire score Sensory reweighting Treatment responder

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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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