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Development of Chinese herbal medicine for sensorineural hearing loss

Acta Pharmaceutica Sinica B 2024年第2期14卷 455-467页

作者： Yunhao Wu Jingwen Zhang Qiuping Liu Zhuang Miao Renjie Chai Wenyong Chen State Key Laboratory of Bioelectronics Department of Otolaryngology Head and Neck SurgeryZhongda HospitalSchool of Life Sciences and TechnologyAdvanced Institute for Life and HealthJiangsu Province HighTech Key Laboratory for Bio-Medical ResearchSoutheast UniversityNanjing 210096China Department of Otolaryngology-Head and Neck the Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120China Department of Otolaryngology-Head and Neck Surgery Affiliated Hospital of Jiangnan UniversityWuxi 214000China Department of Otolaryngology Head and Neck Surgery Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610000China Co-Innovation Center of Neuroregeneration Nantong UniversityNantong 226001China Institute for Stem Cell and Regeneration Chinese Academy of ScienceBeijing 100085China Beijing Key Laboratory of Neural Regeneration and Repair Capital Medical UniversityBeijing 100069China

According to the World Health Organization’s world report on hearing,nearly 2.5 billion people worldwide will suffer from hearing loss by 2050,which may contribute to a severe impact on individual life quality and national economies.sensorineural hearing loss(SNHL)occurs commonly as a result of noise exposure,aging,and ototoxic drugs,and is pathologically characterized by the impairment of mechanosensory hair cells of the inner ear,which is mainly triggered by reactive oxygen species accumulation,inflammation,and mitochondrial dysfunction.Though recent advances have been made in understanding the ability of cochlear repair and regeneration,there are still no effective therapeutic drugs for SNHL.Chinese herbal medicine which is widely distributed and easily accessible in China has demonstrated a unique curative effect against SNHL with higher safety and lower cost compared with Western medicine.Herein we present trends in research for Chinese herbal medicine for the treatment of SNHL,and elucidate their molecular mechanisms of action,to pave the way for further research and development of novel effective drugs in this field.

关键词： sensorineural hearing loss Chinese herbal medicine Molecular mechanism Active ingredients Prescriptions Ototoxic drugs Noise Hair cells

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Intratympanic injection of hydrogel nanodrug for the prevention and treatment of sensorineural hearing loss

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中华耳科学杂志:英文版 2023年第4期18卷 235-239页

作者： Tianying Zhai Pingping Ai Zhaohui Tang Chaoliang He Xuesi Chen Shiming Yang Nan Wu Senior Department of Otolaryngology-Head&Neck Surgery PLA General HospitalBeijingChina National Clinical Research Center for Otolaryngologic Disease BeijingChina State Key Lab of hearing Science Ministry of EducationBeijingChina Beijing Key Lab of hearing Impairment Prevention&Treatment BeijingChina Zhejiang Chinese Medical University HangzhouChina Changchun Institute of Applied Chemistry Chinese Academy of SciencesChangchunChina

Safe and efficient drug delivery to the inner ear has always been the focus of prevention and treatment of sensorineural deafness.The rapid development of nanodrug delivery systems based on hydrogel has provided a new opportunity.Among them,thermo-sensitive hydrogels promote the development of new dosage form for intratympanic injection.This smart biomaterial could transform to semisolid phase when the temperature increased.Thermo-sensitive hydrogel nanodrug delivery system is expected to achieve safe,efficient,and sustained inner ear drug administration.This article introduces the key techniques and the latest progress in this field.

关键词： Thermo-sensitive hydrogel Nanodrug sensorineural hearing loss Intratympanic injection

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Type 2 reaction associated sensorineural hearing loss in a drug resistant lepromatous leprosy patient: A case report

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Asian Pacific Journal of Tropical Medicine 2023年第9期16卷 425-427,I0001页

作者： Harpreet Singh Pawar Itu Singh Harish Kumar Sagar ICMR-National JALMA Institute for Leprosy&Other Mycobacterial Diseases AgraIndia Stanley Browne Research Laboratory the Leprosy Mission(TLM)Community HospitalNew DelhiIndia

Rationale:Leprosy,a chronic granulomatous disease often present clinically as erythema nodosum leprosum,a type 2 reaction.The involvement of cochlear part of audiovestibular system is a rarity.Patient concerns:A 26-year-old male patient with lepromatous leprosy developed bilateral sensorineural hearing loss(SNHL)during type 2 reactional episode.Diagnosis:Recurrent erythema nodosum leprosum in rifampicin-resistant lepromatous leprosy.Interventions:Corticosteroids and second-line multidrug therapy.Outcomes:The patient improved significantly and was further referred for management of psychosocial impact due to sensorineural hearing loss.Lessons:The hearing impairment is a rare complication of type 2 reaction.Any patient with suspected cranial nerve involvement should essentially be screened by tuning fork tests for early detection of hearing impairment and offer timely intervention as required.All high bacteriological index cases should be investigated for antimicrobial resistance in high endemic areas.

关键词： Leprosy reactions Erythema nodosum leprosum sensorineural hearing loss Drug resistant leprosy

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Missing perilymph but leaking blood-endolymph and vestibulocochlear nerve barriers in idiopathic sudden sensorineural hearing loss:A case study

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Journal of Otology 2020年第4期15卷 171-173页

作者： Jing Zou Department of Otolaryngology-Head and Neck Surgery Center for Otolaryngology-Head&Neck Surgery of Chinese PLAChanghai HospitalSecond Military Medical UniversityShanghaiChina

Objectives:To evaluate the pathological changes in the blood-perilymph,blood-endolymph,and bloodnerve barriers of a patient with idiopathic sudden sensorineural hearing loss(SSNHL).Methods:Potential ossification or fibrosis in the inner ear was evaluated using temporal bone CT and MRI acquired using the 3-dimensional T2-weighted sampling perfection with application-optimized contrasts using a flip angle evolution sequence.Pathological changes in the barriers were analyzed by MRI obtained 4 h after a single-dose intravenous injection of gadolinium chelate using a medium inversiontime inversion recovery imaging with magnitude reconstruction sequence.Results:The perilymph was absent,while significant enhancements of the vestibulocochlear nerve and the endolymphatic compartments were detected.Conclusion:Significant injuries in the blood-endolymph and blood-vestibulocochlear nerve barriers and disabled perilymph production may contribute to the development of SSNHL with poor response to treatments.

关键词： sensorineural hearing loss MRI Biological barrier Enhancement

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Cochlear stem cell transplantation for hearing recovery in a rat model of sensorineural hearing loss

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Neural Regeneration Research 2010年第11期5卷 833-837页

作者： Hongyan Zheng Haoqing Tai Shuilin Zeng Department of Anatomy Nanjing University of Traditional Chinese Medicine Nanjing 210029 Jiangsu Province China Institute of Neurobiology Southeast University Medical School Nanjing 210009 Jiangsu Province China

BACKGROUND： Transplantation of in vitro, cultured, neural stem cells or bone marrow stem cells into the cochlear wall or oval window has been used to observe survival, proliferation, and differentiation of cochlear stem cells, as well as migration of differentiated hair cells in scala tympani over a short period of time. OBJECTIVE： To investigate the relationship between survival, proliferation, differentiation, and migration of transplanted cochlear stem cells and hearing recovery from sensorineural hearing loss. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of Neurobiology, Southeast University in 2009. MATERIALS： Stem cells were isolated from neonatal rats, followed by primary and passaged cultures. METHODS： A total of 30 adult, male rats with normal hearing were treated with gentamicin sulfate to establish models of sensorineural hearing loss. The model rats were randomly assigned to cochlear stem cell transplantation and control groups, which were respectively injected with a 10μL cochlear stem cell suspension （1 × 10^5μL） and phosphate-buffered saline into the scala tympani. MAIN OUTCOME MEASURES： Rat hearing recovery was detected by brainstem auditory-evoked potential at 1, 9, and 15 months following transplantation. The location of stem cells was detected using nestin immunofluorescence, proliferative capacity was detected using bromodeoxyuridine immunofluorescence, and hair cell differentiation was detected using Myosin VIIA immunofluorescence. RESULTS： Cochlear stem cells migrated from the needle track to the spiral organ along the scala tympani following transplantation, and the hair cell-like cells migrated to the basal membrane and organ of Corti. The threshold of brainstem auditory-evoked potential increased with increasing time （P 〈 0.05）. CONCLUSION： Transplanted cochlear stem cells from the internal ear migrated to the basal membrane and reached the injury site. The cells differentiated into cells with internal ear functions to improve heari

关键词： cochlear stem cells transplantation hearing recovery sensorineural hearing loss neural regeneration rats

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Improvement in word recognition following treatment failure for sudden sensorineural hearing loss

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2016年第3期2卷 -页

作者： Taha A. Jan Elliott D. Kozin Vivek V. Kanumuri Rosh K. Sethi David H. Jung Department of 0tolaryngology Massachusetts Eye and Ear Infirmary Harvard Medical School Boston MA 02114 USA

UNASSIGNED:Patients with sudden sensorineural hearing loss (SSNHL) may have word recognition scores (WRS) that correlate with pure tone average (PTA). We hypothesize that there is a subset of patients with SSNHL who have improved WRS despite stable PTA.;UNASSIGNED:Retrospective case review at a tertiary otolaryngology practice.;UNASSIGNED:We identified 13 of 113 patients with SSNHL whose WRS increased despite overall stable pure tone averages. There was an observed average improvement in WRS by 23.8 points in this patient cohort at follow-up, with mean initial PTA in the affected ear at 48.7 dB.;UNASSIGNED:We identify a novel cohort of SSNHL patients that have failed treatment as measured by PTA, but who have increased WRS over time. These data have implications for patient counseling and lend insight into the pathophysiology of SSNHL.

关键词： Pure tone average sensorineural hearing loss Sudden sensorineural hearing loss Word recognition score

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Severe dengue associated with aseptic meningitis, acute kidney injury, and sudden sensorineural hearing loss: A case report

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Asian Pacific Journal of Tropical Medicine 2021年第4期14卷 187-190页

作者： Renan GM Diniz Elaine C dos Santos Gabriel CL Chagas Elizabeth F Daher Department of Internal Medicine Faculty of MedicineFederal University of CearaCearaBrazil Department of Intensive Care Unit Fortaleza General HospitalFortalezaCearaBrazil Post-Graduation Program in Medical Sciences Department of Internal MedicineFederal University of CearaFortalezaCearaBrazil

Rationale:Dengue is the most important human arboviral disease.Neurological manifestations occur rarely in dengue.To the best of our knowledge,there is only one reported case of dengue-associated sudden sensorineural hearing loss(SSNHL)in Brazil untill now.Patient concerns:A 42-year-old man was presented to the emergency department with unconsciousness and generalized tonicclonic seizures.Diagnosis:Dengue-associated aseptic meningitis,acute kidney injury,and SSNHL.Interventions:The patient was treated with anticonvulsants and thiamine and underwent mechanical ventilation.He received combined ceftriaxone and acyclovir,which were later switched to meropenem,acyclovir and ampicillin empirically until culture results became available.He also required hemodialysis and plasmapheresis sessions and fresh frozen plasma and buffy coat transfusions until definitive diagnosis.Outcomes:The patient was discharged after improvement of his general condition and of his blood test results,but hearing loss remained.A six-month follow-up visit showed persistent deafness.Lessons:Dengue should be included in the differential diagnosis of patients from dengue-endemic areas presenting an acute febrile disease with neurological manifestations.To the best of our knowledge,this is the second reported case of dengueassociated SSNHL,suggesting an association between dengue and development of SSNHL.

关键词： Dengue Aseptic meningitis Acute kidney injury sensorineural hearing loss Deafness

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Involvement of NLRP3-inflammasome pathway in noise-induced hearing loss

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Neural Regeneration Research 2022年第12期17卷 2750-2754页

作者： Na Sai Yuan-Yuan Yang Long Ma Da Liu Qing-Qing Jiang Wei-Wei Guo Wei-Ju Han College of Otolaryngology Head and Neck Surgery Chinese PLA General HospitalBeijingChina National Clinical Research Center for Otolaryngologic Diseases BeijingChina Key Laboratory of hearing Science Ministry of EducationBeijingChina Beijing Key Laboratory of hearing Impairment for Prevention and Treatment BeijingChina Department of Otolaryngology Head and Neck Surgery Peking University Shenzhen HospitalShenzhenGuangdong ProvinceChina PLA Rocket Force Characteristic Medical Center Department of Stomatology China

The inflammasome is a multiprotein oligomer in the cell cytoplasm and is part of the innate immune system.It plays a crucial role in the pathological process of noise-induced hearing loss(NIHL).However,the mechanisms of NLR family pyrin domain containing 3(NLRP3)inflammasome activation in NIHL have not been clearly demonstrated.In this study,miniature pigs were exposed to white noise at 120 dB(A)and auditory brainstem response measurements were used to measure their hearing function.Immunofluorescence staining,confocal laser scanning microscopy,western blot assay,and quantitative reverse transcription-polymerase chain reaction were used to analyze inflammasome-related protein distribution and expression.NLRP3,interleukin-1β,interleukin-18,and cleaved-caspase-1 were highly expressed in the cochlea after 120 dB(A)white noise exposure.Our findings suggest that NLRP3-inflammasomes in the cochlea may be activated after acoustic trauma,which may be an important mechanism of noise-induced hearing loss.

关键词： acoustic injury inflammasome interleukin-1β miniature pig NLR family pyrin domain containing 3(NLRP3) noise-induced hearing loss sensorineural hearing loss

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Relationship between the external aperture and hearing loss in large vestibular aqueduct syndrome

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Chinese Medical Journal 2006年第3期119卷 211-216页

作者： ZHANG Su-zhen YANG Wei-yan WU Zi-ming Department of Otorhinolaryngology Head and Neck SurgeryGeneral Hospital of Chinese PLA Beijing 100853 China

Backgroud Large vestibular aqueduct syndrome （LVAS） is a major cause of hearing loss in childhood. This study aimed at measuring external aperture of enlargement of the vestibular aqueduct （EVA） and analyzing relationship between the size of external aperture and hearing loss. Methods Diagnostic criteria of LVAS were based on hearing loss and CT images. CT images of temporal bone of 100 LVAS patients were collected and 60 control subjects were reviewed retrospectively in the past 10 years. A battery of audiometric and vestibular function tests were performed. The width of the vestibular aqueduct （VA） was measured on axial CT images of the temporal bone. Results One hundred patients （65 men, 35 women） were diagnosed as having the isolated EVA. hearing loss mostly occurred in early childhood. The diagnosis age of LVAS was 7.7 years on average. The causes of hearing loss could not be confirmed by initial consult. Typically, audiometric curve is the high-frequency down-sloping configuration. 92% of the cases had severe or profound sonsorineural hearing loss （SNHL）. The mean size of the external aperture was （7.5±1.2） mm in present LVAS. Statistical analysis showed that the degree of hearing loss is unrelated to the width of VA. Conclusions LVAS is a distinct clinical entity characterized by fluctuating, progressive SNHL. The degree of hearing loss is unrelated to the size of external aperture of VA. The protective management and hearing aid have become the main therapies. The cochlear implantation might be performed if the hearing loss affected learning at school.

关键词： large vestibular aqueduct syndrome external aperture endolymphetic sac sensorineural hearing loss

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Intracochlear schwannoma: Imaging diagnosis

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Journal of Otology 2023年第2期18卷 101-103页

作者： Safaa Choayb Yahya El Harras Meriem Fikri Najoua Ech-Cherif El Kettani Mohamed Jiddane Firdaous Touarsa Neuroradiology Department Ibn Sina University Hospital CenterRabatMorocco

Intralabyrinthine schwannomas(ILS)are rare benign tumors,often responsible for hearing loss.MRI is important in establishing the diagnosis.We present the example of a 48-year-old lady who reported a 3-years history of right-sided sensorineural deafness.MRI demonstrated a loss of the normal hypersignal of the second turn of the right cochlea compatible with intracochlear schwannoma.

关键词： Intracochlear schwannoma Intralabyrinthine schwannoma sensorineural hearing loss

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