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hearing loss and tinnitus associated with COVID-19 vaccines:An analysis from the national pharmacovigilance database in Malaysia

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Asian Pacific Journal of Tropical Medicine 2023年第7期16卷 289-295,I0002-I0004页

作者： Sing Chet Lee Wee Kee Wo Hee Sheong Yeoh Sim Mei Choo Azuana Ramli National Pharmaceutical Regulatory Agency(NPRA) Ministry of HealthMalaysia

Objective:To compare the reporting pattern of hearing loss and tinnitus across different vaccines brands used in Malaysia(BNT162b2,CoronaVac,ChAdOx1,Ad5.CoV2-S and BBIBP-CorV).Methods:This retrospective study included all reports of hearing loss and tinnitus occurring after COVID-19 vaccination that were received in the national pharmacovigilance database,QUEST,from February 24,2021 through July 31,2022.Reports given causality consistent or indeterminate were included.Results:There were 21 cases of hearing loss,with overall reporting rate of 0.29 cases per million doses.The rate was similar across BNT162b2,CoronaVac and ChAdOx1.For tinnitus,35 cases were reported,with the overall reporting rate of 0.49 cases per million doses,and the highest rate was reported for ChAdOx1.For both events,most cases aged 30 to 49 years.No gender disparity was observed.Both events were mainly reported to have occurred after the primary doses,with a median time-to-onset of two days.There were no statistically significant differences in the reporting patterns for both events across BNT162b2,CoronaVac and ChAdOx1 by age group,gender,race,and dose number.Conclusions:Despite the low reporting rates and insufficient evidence to confirm its relationship,hearing loss and tinnitus following vaccinations should not be ignored due to its disabling potential and impact on one’s quality of life.Continual reporting is encouraged for better signal characterization in the future.

关键词： COVID-19 vaccines hearing loss Tinnitus Adverse events following immunization

Inhibition of histone methyltransferase PRMT5 attenuates cisplatininduced hearing loss through the PI3K/Akt-mediated mitochondrial apoptotic pathway

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Journal of Pharmaceutical Analysis 2023年第6期13卷 590-602页

作者： Zhiwei Zheng Benyu Nan Chang Liu Dongmei Tang Wen Li Liping Zhao Guohui Nie Yingzi He ENT Institute and Department of Otorhinolaryngology Eye&ENT HospitalState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceNHC Key Laboratory of Hearing Medicine(Fudan University)Fudan UniversityShanghai200031China Department of Otorhinolaryngology-Head and Neck Surgery The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical UniversityWenzhou325000ZhejiangChina Department of Otolaryngology-Head and Neck Surgery The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou510630China Department of Otolaryngology Shenzhen Institute of Translational MedicineShenzhen Second People's HospitalThe First Affiliated Hospital of Shenzhen UniversityShenzhen518035GuangdongChina

This study aimed to evaluate the therapeutic potential of inhibiting protein arginine methyltransferase 5(PRMT5)in cisplatin-induced hearing loss.The effects of PRMT5 inhibition on cisplatin-induced auditory injury were determined using immunohistochemistry,apoptosis assays,and auditory brainstem response.The mechanism of PRMT5 inhibition on hair cell survival was assessed using RNA-seq and Cleavage Under Targets and Tagment-quantitative polymerase chain reaction(CUT&Tag-qPCR)analyses in the HEI-OC1 cell line.Pharmacological inhibition of PRMT5 significantly alleviated cisplatin-induced damage to hair cells and spiral ganglion neurons in the cochlea and decreased apoptosis by protecting mitochondrial function and preventing the accumulation of reactive oxygen species.CUT&Tag-qPCR analysis demonstrated that inhibition of PRMT5 in HEI-OC1 cells reduced the accumulation of H4R3me2s/H3R8me2s marks at the promoter region of the Pik3ca gene,thus activating the expression of Pik3ca.These findings suggest that PRMT5 inhibitors have strong potential as agents against cisplatininduced ototoxicity and can lay the foundation for further research on treatment strategies of hearing loss.

关键词： Protein arginine methyltransferase 5 (PRMT5) LLY-283 Cisplatin hearing loss Hair cell Spiral ganglion neuron

Astaxanthine attenuates cisplatin ototoxicity in vitro and protects against cisplatin-induced hearing loss in vivo

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Acta Pharmaceutica Sinica B 2022年第1期12卷 167-181页

作者： Benyu Nan Zirui Zhao Kanglun Jiang Xi Gu Huawei Li Xinsheng Huang Department of Otorhinolaryngology-Head and Neck Surgery Zhongshan HospitalFudan UniversityShanghai 200030China Department of Otorhinolaryngology-Head and Neck Surgery Wenzhou Medical UniversityAffiliated Hospital 2Wenzhou 325000China Department of Otolaryngology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 200437China Department of Otolaryngology the First Affiliated Hospital of Fujian Medical UniversityFuzhou 350005China ENT Institute and Department of Otorhinolaryngology Eye&ENT HospitalState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceFudan UniversityShanghai 200031China Institutes of Biomedical Sciences Fudan UniversityShanghai 200031China NHC Key Laboratory of hearing Medicine(Fudan University) Shanghai 200031China The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science Fudan UniversityShanghai 200031China

Astaxanthine(AST) has important biological activities including antioxidant and antiinflammatory effects that could alleviate neurological and heart diseases, but its role in the prevention of cisplatin-induced hearing loss(CIHL) is not yet well understood. In our study, a steady interaction between AST and the E3 ligase adapter Kelch-like ECH-associated protein 1, a predominant repressor of nuclear factor erythroid 2-related factor 2(NRF2), was performed and tested via computer molecular docking and dynamics. AST protected against cisplatin-induced ototoxicity via NRF2 mediated pathwayusing quantitative PCR and Western blotting. The levels of reactive oxygen species(ROS) and mitochondrial membrane potential revealed that AST reduced ROS overexpression and mitochondrial dysfunction.Moreover, AST exerted anti-apoptosis effects in mouse cochlear explants using immunofluorescence staining and HEI-OC1 cell lines using quantitative PCR and Western blotting. Finally, AST combined with poloxamer was injected into the middle ear through the tympanum, and the protection against CIHL was evaluated using the acoustic brain stem test and immunofluorescent staining in adult mice. Our results suggest that AST reduced ROS overexpression, mitochondrial dysfunction, and apoptosis via NRF2-mediated pathway in cisplatin-exposed HEI-OC1 cell lines and mouse cochlear explants, finally promoting cell survival. Our study demonstrates that AST is a candidate therapeutic agent for CIHL.

关键词： Astaxanthine Cisplatin hearing loss Mitochondrial Ototoxicity Reactive oxygen species Apoptosis

Effect of minocycline and its nano-formulation on central auditory system in blast-induced hearing loss rat model

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Journal of Otology 2023年第1期18卷 38-48页

作者： Venkatesan Perumal Arun Reddy Ravula Ningning Shao Namas Chandra Center for Injury Biomechanics Materialsand MedicineDepartment of Biomedical EngineeringNew Jersey Institute of TechnologyNewarkNJ07102USA

Blast injuries are common among the military service members and veterans.One of the devastating effects of blast wave induced TBI is either temporary or permanent hearing loss.Treating hearing loss using minocycline is restricted by optimal drug concentration,route of administration,and its half-life.Therefore,therapeutic approach using novel therapeutic delivery method is in great need.Among the different delivery methods,nanotechnology-based drug delivery is desirable,which can achieve longer systemic circulation,pass through some biological barriers and specifically targets desired sites.The current study aimed to examine therapeutic effect of minocycline and its nanoparticle formulation in moderate blast induced hearing loss rat model through central auditory system.The I.v.administered nanoparticle at reduced dose and frequency than regularly administered toxic dose.After moderate blast exposure,rats had hearing impairment as determined by ABR at 7-and 30-days post exposure.In chronic condition,free minocycline also showed the significant reduction in ABR threshold.In central auditory system,it is found in this study that minocycline nanoparticles ameliorate excitation in inferior colliculus;and astrocytes and microglia activation after the blast exposure is reduced by minocycline nanoparticles administration.The study demonstrated that in moderate blast induced hearing loss,minocycline and its nanoparticle formulation exhibited the optimal therapeutic effect on the recovery of the ABR impairment and a protective effect through central auditory system.In conclusion,targeted and non-targeted nanoparticle formulation have therapeutic effect on blast induced hearing loss.

关键词： Minocycline Nanoparticle hearing loss Blast injury and targeted drug delivery

The portrayal of hearing loss information in online Mandarin videos

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Journal of Otology 2023年第3期18卷 152-159页

作者： Chandan H.Suresh Kiara Leng Nilesh J.Washnik Satyabrata Parida Department of Communication Disorders California State UniversityLos AngelesUSA Department of Communication Sciences and Disorders Ohio UniversityAthensOHUSA Department of Neurobiology University of PittsburghPittsburghPA15261USA

Background/purpose:With increasing accessibility to the Internet,patients frequently use the Internet for hearing healthcare information.No study has examined the information about hearing loss available in the Mandarin language on online video-sharing platforms.The study’s primary purpose is to investigate the content,source,understandability,and actionability of hearing loss information in the Mandarin language’s one hundred most popular online videos.Method:In this project,publicly accessible online videos were analyzed.One hundred of the most popular Mandarin-language videos about hearing loss were identified(51 videos on YouTube and 49 on the Bilibili video-sharing platform).They were manually coded for different popularity metrics,sources,and content.Each video was also rated using the Patient Education Materials Assessment Tool for Audiovisual Materials(PEMAT-AV)to measure the understandability and actionability scores.Results:The video sources were classified as either media(n=36),professional(n=39),or consumer(n=25).The videos covered various topics,including symptoms,consequences,and treatment of hearing loss.Overall,videos attained adequate understandability scores(mean=73.6%)but low(mean=43.4%)actionability scores.Conclusions:While existing online content related to hearing loss is quite diverse and largely understandable,those videos provide limited actionable information.hearing healthcare professionals,media,and content creators can help patients better understand their conditions and make educated hearing healthcare decisions by focusing on the actionability information in their online videos.

关键词： hearing loss YouTube BiliBili Internet health information Social media

Yellow responsive material based modification to reduce earphone induced Infection and hearing loss

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Nano Research 2022年第7期15卷 6297-6305页

作者： Haoxin Cheng Hongmei Liu Zhiqiang Liu Ziying Xu Xiaorong Liu Shuang Jia Chaonan He Shichen Liu Jiao Zhang Xiaolei Wang College of Chemistry Nanchang UniversityNanchang 330088China The National Engineering Research Center for Bioengineering Drugs and the Technologies Institute of Translational MedicineNanchang UniversityNanchang 330088China The First Clinical Medical School Nanchang UniversityNanchang 330088China The Stomatological School Nanchang UniversityNanchang 330088China The Department of Vascular Surgery the Second Affiliated Hospital of Nanchang UniversityNanchang UniversityNanchang 330006China

Today,earphones have almost been owned by everyone.However,wearing earphones for a long time can cause two serious problems:(1)irreversible damage to hearing;(2)rapid proliferation of bacteria in the ear canal.Herein,an earphone modification strategy is developed for the first time,to reduce hearing loss and inhibit bacteria simultaneously.This earphone is equipped with a high purity yellow light(YL)light-emitting diode chip developed by our university.Then,the surface of the earphone is loaded with porous zinc oxide and silver nanoparticle composite material(ZnO-Ag)that can respond to the YL.Under the excitation of YL,the porous ZnO-Ag can release reactive oxygen species with strong antibacterial activity.More importantly,we discover that YL can reduce the expression of matrix metalloproteinase-3,the secretion of inflammatory factors,and apoptosis in the cochlea,thereby effectively reduce hearing loss.

关键词： ZnO yellow light antibacterial activity hearing loss earphone

Ionically Imprinting-Based Copper(Ⅱ)Label-Free Detection for Preventing hearing loss

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Engineering 2024年第2期33卷 276-282页

作者： Huan Wang Hui Zhang Xiaoli Zhang Hong Chen Ling Lu Renjie Chai The Eighth Affiliated Hospital Sun Yat-Sen UniversityShenzhen 518033China State Key Laboratory of Digital Medical Engineering Department of Otolaryngology Head and Neck SurgeryZhongda Hospital&Advanced Institute for Life and HealthSoutheast UniversityNanjing 210096China Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging Department of Biomedical EngineeringShenzhen UniversityShenzhen 518060China Department of Otolaryngology Head and Neck Surgery Jiangsu Provincial Key Medical DisciplineNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China Co-Innovation Center of Neuroregeneration Nantong UniversityNantong 226001China Department of Otolaryngology Head and Neck Surgery Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610072China Institute for Stem Cell and Regeneration Chinese Academy of ScienceBeijing 100101China Beijing Key Laboratory of Neural Regeneration and Repair Capital Medical UniversityBeijing 100069China

Copper is a microelement with important physiological functions in the body.However,the excess copper ion(Cu^(2+))may cause severe health problems,such as hair cell apoptosis and the resultant hearing loss.Therefore,the assay of Cu^(2+)is important.We integrate ionic imprinting technology(IIT)and structurally colored hydrogel beads to prepare chitosan-based ionically imprinted hydrogel beads(IIHBs)as a low-cost and high-specificity platform for Cu^(2+)detection.The IIHBs have a macroporous microstructure,uniform size,vivid structural color,and magnetic responsiveness.When incubated in solution,IIHBs recognize Cu^(2+)and exhibit a reflective peak change,thereby achieving label-free detection.In addition,benefiting from the IIT,the IIHBs display good specificity and selectivity and have an imprinting factor of 19.14 at 100μmol·L^(-1).These features indicated that the developed IIHBs are promising candidates for Cu^(2+)detection,particularly for the prevention of hearing loss.

关键词： Structural color Microfluidics Ionic imprinting Label-free detection hearing loss

Effect of N-acetyl-cysteine treatment on sensorineural hearing loss: a meta-analysis

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2022年第3期8卷 205-212页

作者： Xue Bai Miao Wang Xun Niu Hong Yu Jian-Xin Yue Yu Sun Department of Otorhinolaryngology Union HospitalTongji Medical CollegeHuazhong University of Scienceand TechnologyWuhan430022China

N-acetyl-cysteine (NAC) is an efficacious treatment for sensorineural hearing loss in animal models, such as noise-induced hearing loss (NIHL), however previous research into the effect of NAC on patients with hearing loss produced contradictory results. In this study, we investigated the effect of NAC treatment on sensorineural hearing loss. PubMed, Web of Science and Embase databases were searched in their entirety using the key words: hearing loss, NAC, N-acetylcysteine, and sensorineural hearing loss. Studies which included assessment of hearing loss with pure-tone threshold (PTA) data were selected. Eligible studies regarding the effects of NAC treatment on patients with hearing loss were collected by two independent reviewers. A total of 1197 individuals were included from seven published studies. Two studies reported data for a sudden idiopathic sensorineural hearing loss (SISNHL) group. Three studies reported data for a NIHL group. Other studies reported data for drug-induced hearing loss. The meta-analysis demonstrated that the overall effect of NAC treatment on sensorineural hearing loss was invalid. However, NAC treatment was linked with improved patient outcomes of hearing tests in cases of sudden hearing loss, but did not prevent hearing loss induced by noise or ototoxicity. However, there is a need for better-designed studies with larger samples to further prove the correlation between the effect of NAC and hearing loss.

关键词： hearing loss Meta-analysis N-acetyl-cysteine

Glucose Protects Cochlear Hair Cells Against Oxidative Stress and Attenuates Noise-Induced hearing loss in Mice

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Neuroscience Bulletin 2021年第5期37卷 657-668页

作者： Hao Xiong Lan Lai Yongyi Ye Yiqing Zheng Department of Otolaryngology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Institute of hearing and Speech-Language Science Sun Yat-sen UniversityGuangzhou 510120China

Oxidative stress is the key determinant in the pathogenesis of noise-induced hearing loss(NIHL). Given that cellular defense against oxidative stress is an energyconsuming process, the aim of the present study was to investigate whether increasing energy availability by glucose supplementation protects cochlear hair cells against oxidative stress and attenuates NIHL. Our results revealed that glucose supplementation reduced the noiseinduced formation of reactive oxygen species(ROS) and consequently attenuated noise-induced loss of outer hair cells, inner hair cell synaptic ribbons, and NIHL in CBA/J mice. In cochlear explants, glucose supplementation increased the levels of ATP and NADPH, as well as attenuating H_2O_2-induced ROS production and cytotoxicity. Moreover, pharmacological inhibition of glucose transporter type 1 activity abolished the protective effects of glucose against oxidative stress in HEI-OC1 cells. These findings suggest that energy availability is crucial for oxidative stress resistance and glucose supplementation offers a simple and effective approach for the protection of cochlear hair cells against oxidative stress and NIHL.

关键词： Oxidative stress Glucose Cochlea Hair cell hearing loss