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

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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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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Vestibular function of pediatric patients with sudden sensorineural hearing loss:based on vertigo symptom and vestibular function testing

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World Journal of pediatrics 2021年第6期17卷 637-642页

作者： Yan-Hong Li Bing Liu Yang Yang Min Chen Wei Liu Jian-Bo Shao Xiao Zhang Jie Zhang Xin Ni Department of Otorhinolaryngology head and neck surgery Beijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijingChina beijing key laboratory for pediatric diseases of otolaryngology head and neck surgery Beijing Pediatric Research InstituteBeijingChina

Background This study aimed to evaluate the relationship between vestibular and auditory functions in pediatric patients with sudden sensorineural hearing loss(SSHL).Methods A total of 30 pediatric patients experiencing unilateral SSHL between 5.9 and 13.0 years of age were enrolled in this *** tone audiometry was evaluated prior to treatment initiation and again after one month of *** to treatment initiation,vertigo symptoms were noted;then several vestibular function tests were conducted including caloric testing,ocular vestibular evoked myogenic potentials(o-VEMPs)and cervical vestibular evoked myogenic potentials(c-VEMPs).Associations between pre and post-treatment vestibular function and hearing threshold levels were *** Initial hearing thresholds of children with vertigo were higher than thresholds of children without vertigo(92 dB vs 79 dB,F=0.033),while initial hearing thresholds of children with abnormal caloric test findings were higher than thresholds of children with normal caloric test findings(93 dB vs 67 dB.P=0.014).Cutoff values of hearing thresholds for those with vertigo symptoms and abnormal vestibular test results were 86.000-and 89.583-dB *** prognosis,children with vertigo exhibited lower recovery rates than children without vertigo(33%vs 75%,P=0.025);recovery rates of children with abnormal caloric test results were lower than the overall recovery rate(25%vs 73%,respectively,P=0.039).Conclusion Assessments of vertigo symptoms and vestibular function are useful tools in predicting pediatric SwSHL patient disease severity and prognosis.

关键词： Prognosis sudden sensorineural hearing loss Vertigo Vestibular function tests

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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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Detection of FOXO1 break-apart status by fluorescence in situ hybridization in atypical alveolar rhabdomyosarcoma

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Science China(Life Sciences) 2017年第7期60卷 721-728页

作者： Libing Fu Yaqiong Jin Chao Jia Jie Zhang Jun Tai Hongbin Li Feng Chen Jin Shi Yongli Guo Xin Ni Lejian He Department of Pathology Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing 100045 China beijing key laboratory for pediatric diseases of otolaryngology Head and Neck Surgery MOE Key Laboratory of Major Diseases in Children Beijing Pediatric Research Institute Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing 100045 China Biobank for Clinical Data and Samples in pediatric Beijing Pediatric Research Institute Beijing Children's Hospital Capital Medical University National Center for Children's Health Belting 100045 China Department of otolaryngology Head and Neck Surgery Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing 100045 China

The morphologies of alveolar rhabdomyosarcoma(ARMS) are various. Some cases entirely lack an alveolar pattern and instead display a histological pattern that overlaps with embryonal rhabdomyosarcoma(ERMS). The method of pathological diagnosis of ARMS and ERMS has been updated in the 4th edition of the World Health Organization's guidelines for classification of skeletal muscle tumors. Under the new guidelines, there is still no molecular test to distinguish between these two subtypes of rhabdomyosarcoma(RMS). In the present study, we applied fluorescent in situ hybridization(FISH) and found that the Forkhead box O1(FOXO1) gene broke apart, amplified, and displayed an aneuploid signal that was related to the RMS pathological *** from the fact that FOXO1 break-apart and its amplification were correlated with atypical ARMS, aneuploidies were usually found in atypical ERMS. In conclusion, our results detail a potential biomarker to improve the accuracy of pathological diagnosis by discriminating between atypical ARMS and atypical ERMS.

关键词： atypical alveolar rhabdomyosarcoma FOXO1 fluorescence in situ hybridization

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A Five-year Surveillance of Carbapenemase-producing Klebsiella pneumoniae in a pediatric Hospital in China Reveals Increased Predominance of NDM-1

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Biomedical and Environmental Sciences 2017年第8期30卷 562-569页

作者： DONG Fang LU Jie WANG Yan SHI Jin ZHEN Jing Hui CHU Ping ZHEN Yang HAN Shu Jing GUO Yong Li SONG Wen Qi Department of laboratory Medicine Beo'ing Children's Hospital Capital Medical University Beijing 100045 China key laboratory of Major diseases in Children Ministry of Education Beijing Pediatric Research Institute Beijing Children's' Hospital Capital Medical University Beijing 100045 China beijing key laboratory for pediatric diseases of otolaryngology Head and Neck Surgery Biobank for Clinical Data and Samples' in Pediatric Beijing Pediatric Research Institute Beijing Children's Hospital Capital Medical University Beijing 100045 China

Objective To characterize carbapenem （CPM）-non-susceptible Klebsiella pneumoniae （K. pneumoniae） and carbape-nemase produced by these strains isolated from beijing Children＇s Hospital based on a five-year surveillance. Methods The Minimal Inhibition Concentration values for 15 antibiotics were assessed using the Phonixl00 compact system. PCR amplification and DNA sequencing were used to detect genes encoding carbapenemases. WHONET 5.6 was finally used for resistance analysis. Results In total, 179 strains of CPM-non-susceptible K. pneumoniae were isolated from January, 2010 to December, 2014. The rates of non-susceptible to imipenem and meropenem were 95.0% and 95.6%, respectively. In the 179 strains, 95 （53.1%） strains carried the blalMP gene, and IMP-4 and IMP-8 were detected in 92 （96.8%） and 3 （3.2%） IMP-producing isolates, respectively. 65 （36.3%） strains carried the blaNDM_1 gene. 6 （3.4%） strains carried the blaKpc gene, and KPC-2 were detected in 6 KPC-producing isolates. In addition, New Delhi-Metallo-1 （NDM-1） producing isolates increased from 7.1% to 63.0% in five years and IMP-4 producing isolates decreased from 75.0% to 28.3%. Conclusion High frequencies of multiple resistances to antibiotics were observed in the CPM-non-susceptible K. pneumoniae strains isolated from beijing Children＇s Hospital. The production of IMP-4 and NDM-1 metallo-13-1actamases appears to be an important mechanism for CPM-non- susceptible in K. pneumoniae.

关键词： Klebsiella pneumoniae Carbapenemases Microbial drug resistance

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Nonlinear dynamic response and stability analysis of the stapes reconstruction in human middle ear

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Applied Mathematics and Mechanics(English Edition) 2023年第10期44卷 1739-1760页

作者： Lele WANG Liang WANG Yueting ZHU Zhanli LIU Yongtao SUN Jie WANG Hongge HAN Shuyi XIANG Huibin SHI Qian DING Department of Mechanics Tianjin UniversityTianjin 300350China Tianjin key laboratory of Nonlinear Dynamics and Control Tianjin UniversityTianjin 300350China Department of otolaryngology Head and Neck SurgeryTianjin Children's HospitalTianjin UniversityTianjin 300400China School of Aerospace Engineering Tsinghua UniversityBeijing 100084China Department of otolaryngology head and neck surgery Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China key laboratory of otolaryngology head and neck surgery Ministry of EducationBeijing 100730China beijing Engineering Research Center of Audiological Technology Beijing 100730China

Stapes fracture causes hearing loss and instability in the middle ear hearing system(MEHS). The material used in the stapes reconstruction restores stapes, but the effects of the nonlinear material parameters on the stability of the MEHS are still unknown. To address this challenge, the nonlinear dynamic response and stability of the stapes reconstruction are investigated using a multi-degree-of-freedom mechanical model. The material parameters of the implant are tentatively determined by analyzing the natural frequencies of the undamped system. The dynamical properties of the MEHS are characterized under different external excitations. The approximate solution of the MEHS near the resonant frequency is derived through the multiple-time-scale method(MTSM). The results show that the nonlinear stiffness of the material has little influence on the MEHS in the healthy state, but it causes resonant phenomena between the ossicle and the implant in the pathological state.

关键词： crus fracture of stapes stapes reconstruction dynamic analysis bifurcation analysis multiple-time-scale method(MTSM)

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The Challenge and promise of rare disease diagnosis in China

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Science China(Life Sciences) 2017年第7期60卷 681-685页

作者： Xin Ni Tieliu Shi otolaryngology Head and Neck Surgery Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing 100045 China beijing key laboratory for pediatric diseases of otolaryngology Head and Neck Surgery Beijing Pediatric Research Institute Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing 100045 China The Center for Bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biology the Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai 200241 China

Rare diseases are chronic and serious,featuring early onset at birth or in childhood,rapid deterioration and high mortality rate,which creates a burden on society and public health *** the known rare diseases,80 percent are genetic in origin,and half of those affected worldwide are *** China,the rare disease patients are over 10 million,and70 percent of the patients are children(Song et al.,2012;Liu et al.,2010).

关键词： deterioration childhood burden children featuring promise birth mortality pediatric distinguished

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Correlation between TERT C228T and clinic-pathological features in pediatric papillary thyroid carcinoma

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Science China(Life Sciences) 2019年第12期62卷 1563-1571页

作者： Jiangqiao Geng Yuanhu Liu Yongli Guo Huanmin Wang Jun Tai Yaqiong Jin Jie Zhang Yongbo Yu Shengcai Wang Yingluan Song Xin Ni otolaryngology Children's Hospital of Hebei ProvinceShijiazhuang 050031China otolaryngology Head and Neck SurgeryBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijing 100045China beijing key laboratory for pediatric diseases of otolaryngology Head and Neck SurgeryBeijing Pediatric Research InstituteBeijing Children's HospitalCapital Medical UniversityNational Center for Childrens HealthBeijing 100045China Department of Surgical Oncology Beijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijing 100045China

The aims of the present study were to reveal the prevalence of the TERT C228 T mutation in pediatric papillary thyroid carcinoma(PPTC) and to further investigate the role of the TERT C228 T mutation in PPTC. We also tested another TERT mutation, TERT C250 T, although this was not detected in PPTC patients. In this study, 48 patients with PPTC(41 with classic PPTC) were enrolled. DNA was extracted from PPTC tissues and TERT C228 T mutation analysis was performed. Chi-squared analysis,Fisher’s exact test, and a t-test were applied to test the significance of differences. The TERT C228 T mutation presented in 13(27.1%) of the 48 PPTC patients and 10(24.4%) of the 41 classical PPTC patients. There were significant differences between PPTC patients with the TERT C228 T mutation and those without in terms of modified radical neck dissection, multifocality,capsular invasion, extrathyroidal invasion, and American Joint Committee on Cancer(AJCC) tumor stage(P<0.05). In classical PPTC, there were additional significant differences in other clinic-pathological features, such as AJCC nodal stage(P=0.009)and American Thyroid Association(ATA) PPTC stage(P=0.021) between patients with and without the TERT C228 T *** findings indicate that the TERT C228 T mutation is significantly correlated with certain aggressive clinic-pathological features of PPTC.

关键词： pediatric papillary thyroid cancer TERT C228T mutation clinic-pathological characteristics

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