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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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Diabetic peripheral neuropathy and neuromodulation techniques:a systematic review of progress and prospects

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Neural Regeneration Research 2025年第8期20卷 2218-2230页

作者： Rahul Mittal Keelin McKenna Grant Keith Evan McKenna Joana R.N.Lemos Jeenu Mittal Khemraj Hirani Diabetes Research Institute University of Miami Miller School of MedicineMiamiFLUSA department of otolaryngology University of Miami Miller School of MedicineMiamiFLUSA Herbert Wertheim College of Medicine Florida International UniversityMiamiFLUSA School of Medicine and Public Health University of WisconsinMadisonWIUSA

Neuromodulation for diabetic peripheral neuropathy represents a significant area of interest in the management of chronic pain associated with this *** peripheral neuropathy,a common complication of diabetes,is characterized by nerve damage due to high blood sugar levels that lead to symptoms,such as pain,tingling,and numbness,primarily in the hands and *** aim of this systematic review was to evaluate the efficacy of neuromodulatory techniques as potential therapeutic interventions for patients with diabetic peripheral neuropathy,while also examining recent developments in this *** investigation encompassed an array of neuromodulation methods,including frequency rhythmic electrical modulated systems,dorsal root ganglion stimulation,and spinal cord *** systematic review suggests that neuromodulatory techniques may be useful in the treatment of diabetic peripheral *** the advantages of these treatments will enable physicians and other healthcare providers to offer additional options for patients with symptoms refractory to standard pharmacologic *** these efforts,we may improve quality of life and increase functional capacity in patients suffering from complications related to diabetic neuropathy.

关键词： diabetes mellitus diabetic peripheral neuropathy neuromodulation neurostimulation therapy non-pharmacological treatment pain management

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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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Herpes simplex virus 2-induced aseptic meningitis presenting with sudden deafness:A case report

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World Journal of Clinical Cases 2025年第8期13卷 22-25页

作者： Yuan-Cheng Liu Shih-Hsuan Hsiao Peir-Rong Chen department of otolaryngology Hualien Tzu Chi HospitalHualien 970TaiwanChina department of otolaryngology Hualien Tzu Chi Hospitaland Department of OtolaryngologyHead and Neck SurgerySchool of MedicineTzu Chi UniversityHualien 970TaiwanChina

BACKGROUND Aseptic meningitis is defined as meningeal inflammation caused by various etio-logies with negative cerebrospinal fluid(CSF)bacterial *** most common etiologies are viruses[enteroviruses,arboviruses,and herpes simplex virus type 2(HSV-2)].Aseptic meningitis can have various presentations,including sensori-neural *** sensorineural deafness from mumps meningoencephalitis has been reported,cases of HSV-2-induced hearing loss are ***,we re-port a case of HSV-2-induced meningitis that presented with sudden *** SUMMARY A 68-year-old man experienced a profound sudden onset of left-sided hearing loss for one ***-tone audiograms demonstrated sudden left-sided sensorineural hearing loss(thresholds 80-90 dB).After treatment with high-dose steroids for 1 week,he experienced an acute consciousness change with left *** laboratory data showed no significant *** computed tomography without contrast and magnetic resonance imaging revealed no intracranial hemo-rrhage or obvious brain *** CSF analysis and the Multiplex PCR panels showed HSV-2 ***,under the diagnosis of herpes meningoenceph-alitis,acyclovir was prescribed and his symptoms gradually *** This case report further demonstrates that a viral infection could be a cause of sudden sensorineural hearing loss.

关键词： Aseptic meningitis Type 2 herpes simplex Sudden sensorineural hearing loss Immunocompromised Cerebrospinal fluid Case report

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Notch pathway inhibitor DAPT enhances Atoh1 activity to generate new hair cells in situ in rat cochleae

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Neural Regeneration Research 2017年第12期12卷 2092-2099页

作者： Wen-wei Luo Zhao Han Dong-dong Ren Xin-wei Wang Fang-lu Chi Juan-mei Yang department of otolaryngology Eye & ENT Hospital of Fudan University Research Institute of otolaryngology Fudan University

Atoh1 overexpression in cochlear epithelium induces new hair cell formation. Use of adenovirus-mediated Atoh1 overexpression has mainly focused on the rat lesser epithelial ridge and induces ectopic hair cell regeneration. The sensory region of rat cochlea is difficult to transfect, thus new hair cells are rarely produced in situ in rat cochlear explants. After culturing rat cochleae in medium containing 10% fetal bovine serum, adenovirus successfully infected the sensory region as the width of the supporting cell area was significantly increased. Adenovirus encoding Atoh1 infected the sensory region and induced hair cell formation in situ. Combined application of the Notch inhibitor DAPT and Atoh1 increased the Atoh1 expression level and decreased hes1 and hes5 levels, further promoting hair cell generation. Our results demonstrate that DAPT enhances Atoh1 activity to promote hair cell regeneration in rat cochlear sensory epithelium in vitro.

关键词： nerve regeneration Atoh 1 DAPT. transdifferentiation gamma secretase inhibitor cochlea sensory epithelium fetal bovine serum hair cell supporting cell hair cell regeneration neural regeneration

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Effect of Zhu-yuan decoction in patients with chronic rhinosinusitis after functional endoscopic sinus surgery

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Journal of Traditional Chinese Medicine 2018年第1期38卷 83-88页

作者： Li Jing Zheng Chunquan Lin Hai Yang Chen Gu Siyuan Wang Yi Duan Honggang department of otolaryngology Hangzhou First People's Hospital Nanjing Medical University department of otolaryngology Eye & ENT Hospital of Fudan University department of otolaryngology the Second Affiliated Hospital of Zhejiang University School of Medicine

OBJECTIVE: To investigate the effectiveness and safety of Zhu-yuan decoction(ZYD) in patients after functional endoscopic sinus surgery(FESS).METHODS: A total of 85 patients were randomized into two groups: 44 were treated with intranasal corticosteroids(INC), and 41 were given Chinese herbal medicine(CHM). Patients with chronic rhinosinusitis(CRS) who underwent FESS were prospectively enrolled in the study. Before surgery, they were evaluated by visual analog scale(VAS), nasal endoscopy, computed tomography(CT), and routine blood test. After surgery, they were randomized to take ZYD or INC for 12 weeks and revaluated by VAS; nasal endoscopy at 4, 8, and 12 weeks;and CT at 12 weeks after ***: In the both groups, VAS and endoscopyscores decreased significantly at 4, 8, and 12 weeks,and CT scores after treatment declined at 12 weeks compared with baseline scores. No significant differences were observed with regard to postoperative VAS, endoscopy, or CT scores between ***, combined with surgery, can reduce VAS, nasal endoscopy, and CT scores and has the same efficacy and safety profile as INC in post-FESS *** fatalities or major adverse events occurred in either ***: Our findings suggest that ZYD has similar effects and safety profiles in patients after FESS compared with INC.

关键词： Chinese herbal medicine Adrenal cortex hormones Chronic rhinosinusitis Functional endoscopic sinus surgery Zhu-yuan decoction

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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： malignant tumor bone tumors

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Prospective study of the prevalence and co-morbidities of obstructive sleep apnea in active-duty army personnel in the three southernmost provinces of Thailand using questionnaire screening

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Military Medical Research 2019年第2期6卷 135-142页

作者： Anisong Pilakasiri Prasit Mahakit department of otolaryngology Phramongkutklao Hospital and College of Medicine

Background: It is crucial for the army to know the prevalence of obstructive sleep apnea(OSA) syndrome in activeduty army personnel. Little information has been reported on the prevalence of OSA and clinical features in activeduty army personnel. This study was aimed to estimate the prevalence of snoring and risk of developing OSA in activeduty army personnel in Thailand and to identify the co-morbidities of OSA. In total, 1107 participants who were aged20–60 years and were deployed to the three southernmost provinces of Thailand were enrolled. All the participants completed the Phramongkutklao(PMK) Hospital OSA Questionnaire that was modified and validated from the Berlin Questionnaire and underwent physical examination. The participants were 1107 active-duty army personnel in the three southernmost provinces of Thailand, both males and females, aged 20–60 ***: The PMK OSA Questionnaire was used to assess the risk of OSA together with interviewing for snoring,fatigue, falling asleep and day-time sleepiness. Physical examination of the neck, chest and hip circumference,and height was performed. Information concerning physical training, co-morbid diseases, smoking and alcoholic consumption was ***: The prevalence of snoring was 58.5, and 4.8% met the PMK OSA Questionnaire criteria, thus indicating a high risk of OSA. The information obtained indicated that laryngopharyngeal reflux(LPR), current smoking and alcoholic consumption were significantly higher in the high-risk OSA ***: Early detection and treatment of OSA in active-duty army personnel are imperative. Physical examination and polysomnography can be used to reveal the high-risk group. High body mess index(BMI), laryngopharyngeal reflux, current smoking and alcoholic consumption are modifiable factors for OSA and are avoidable. A policy to decrease the BMI and risk of LPR, as well as to stop smoking and alcoholic consumption, should be applied.

关键词： Active-duty army personnel Laryngopharyngeal reflux Prevalence Questionnaire Snoring Obstructive sleep apnea

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To understand the brain – the 2016 annual meeting of society for neurosciences:a conference report

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Neural Regeneration Research 2016年第12期11卷 1912-1913页

作者： Yike Li department of otolaryngology Vanderbilt University

Overview：Over 30,000 neuroscientists participated in the 46^th annual meeting of the Society for Neurosciences（Sf N 2016）,which was held in San Diego,California from November 12th to 16^*** than 15,000 research pro... 详细信息

关键词： the 2016 annual meeting of society for neurosciences To understand the brain

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