Abstract:Meniere's disease(MD)is an inner ear disorder with a complex etiology and high disease heterogeneity.Recent studies suggest that immune system dysfunction may play a critical role in its pathogenesis and progression.This review summarizes the immune mechanisms underlying MD,with a focus on its comorbid autoimmune diseases,and provides a comprehensive overview of the latest findings in immune cells,cytokines,and proteomic studies.Dysregulated innate and adaptive immune responses,along with abnormal expression of related immune mediators,contribute to the disruption of the inner ear immune microenvironment.In addition,proteomic analyses have identified a series of MD-related biomarkers,which may facilitate disease diagnosis,staging and the development of personalized therapeutic strategies.In conclusion,the immunological basis of MD is gradually being elucidated,suggesting that it may represent a subtype of autoimmune-related disorders.Targeted interventions aimed at immune pathways may provide more precise therapeutic approaches for MD patients in the future.

Abstract:Objective To report rates of energy absorbance(EA)in wideband tympanometry in normal adults and influencing factors.Methods A total of 148 normal hearing individuals(296 ears)undergoing hearing screening at Nanjing Drum Tower Hospital affiliated with Nanjing University from 2020 to 2021 were recruited(mean age=34.34±10.77 years).Tympanometry at 226 Hz showed type A tympanograms in all subjects.Wideband tympanometry covering 122 frequencies from 226 to 8000 Hz were performed to acquire peak pressure frequency-absorbance curves and average tympanograms for comparisons between age,gender and external auditory canal volume.Results(1)The peak pressure frequency-absorbance curve and average tympanogram pattern were similar across the subjects,with the peak pressure frequency-absorbance curve rose from 226 Hz to the first peak at 2519.84 Hz with an EA of 0.811,stable from 2529.84 to 2593.68 Hz and then declining from 2593.68 to 6727.17 Hz ending with an EA of 0.314,followed by an upward trend from there to 8000 Hz.The average peak was similar to the typical tympanogram at 226 Hz,with a peak pressure of-3.7±11.86 daPa and an EA of 0.50±0.12.(2)EA in wideband tympanometry was mainly influenced by gender and external auditory canal volume as two independent factors(P>0.05),with gender showing an impact on peak pressure EA in the 226～1000 Hz,2 kHz,3～5 kHz and 6.5～8 kHz frequency ranges(P<0.05),and external auditory canal volume in the 226～1000 Hz,1.7～2.1 kHz,2.5～6 kHz and 7～8 kHz frequency ranges(P<0.05).On average tympanogram,effects of gender were visible in the+150 to-13 daPa and-81 to-300 daPa pressure ranges(P<0.05),while effects of external auditory canal volume were seen at every sampling point(P<0.001).Conclusions Among young and middle-aged adults with normal middle ears,gender and external auditory canal volume are the main factors influencing acoustic mechanical characteristics in wideband tympanometry independent of each other.The influence of these two factors should be considered when establishing normative values to improve the accuracy and sensitivity of middle ear disease diagnosis.

Abstract:Objective To report clinical characteristics and therapeutic outcomes of manual repositioning in 10 children with benign paroxysmal positional vertigo(BPPV).Methods Clinical data of 10 pediatric patients with BPPV treated in our department from January 2020 to June 2023 were retrospective analyzed,There were 7 males and 3 females,aged from 4 to 14 years.Fill in the questionnaire after further clinical diagnosis according to the patient's medical history and symptoms,and relieve the dizziness symptoms of the children through interesting vestibular rehabilitation training such as ball tossing game and balance board game,focusing on clinical characteristics and therapeutic effects of manual repositioning with follow-up.Results Nine children were diagnosed with BPPV by position test(including roll test and Dix Hallpike test),and one case was suspected of BPPV.The specific diagnosis distribution was:left posterior semicircular canal BPPV in 3 cases,right posterior semicircular canal BPPV in 2 cases,left horizontal semicircular canal BPPV in 3 cases,right horizontal semicircular canal BPPV in 1 case,suspected right horizontal semicircular canal BPPV in 1 case.Treatment effect:all children received manual reduction treatment and interesting vestibular function rehabilitation training,and the total cure rate reached 100%.Conclusions The diagnosis of pediatric BPPV mainly relies on typical vertigo history and positional tests.Manual repositioning is effective and safe,making it the preferred treatment for pediatric BPPV.

Abstract:Objective To demonstrate suppression of can noise-induced cochlear inflammation by TLR4 blocker in protecting hearing function.Methods SD rats were randomly divided into a normal control group,a noise exposure group,a noise explore with intratympanic TAK242(a TLR4 inhibitor)injection group,and a noise explore with intratympanic DMSO injection group.Auditory brainstem response(ABR)data were collected on the 3rd and 14th days post noise exposure.On the 3rd day post noise exposure,the cochlea was harvested to measure TLR4,myeloid differentiation factor 88(MyD88),IL-1β and TNF-αby western blot and immunohistochemistry,and to measure NF-κB p65 activity with immunofluorescence staining.TUNEL assay was used to display apoptotic cells.Results After noise explore,the expression of TLR4,MyD88,NF-κB and TNF-α was significantly elevated in the spiral ligament,spiral ganglion neuron and Deiters'cells.In stria vascularis,the expression of TLR4,NF-κB and TNF-α was consistently increased,while MyD88 showed no significant change.TAK242 treated rats showed significantly lower expression of MyD88,IL-1βand TNF-α,lower activity of NF-κB,and fewer apoptotic cells in spiral limbus,compared to untreated rats,as well as better ABR responses.Conclusions TLR4 inhibitors can suppress noise induced inflammation in the spiral ligament,stria vascularis,spiral ganglion and organ of Corti,thus protecting hearing function.

Abstract:This article summarizes the efficacy of application of the UpToDate database combined with digital video otoscopy in otology clinical teaching,aiming to address the issues of limited resources and monotonous methods in traditional teaching models.By detailing the characteristics and functions of the UpToDate database and digital video otoscopy,the theoretical basis for their combined use is elaborated.In addition,practical teaching cases are used to demonstrate their advantages in teaching scheme design,process implementation,and teaching effectiveness.This integrated application approach has the potential to enrich educational resources,and improve the intuitiveness and interactivity of teaching.It also assists students in developing self-directed learning abilities and clinical reasoning skills,thereby providing novel perspectives and methodologies for clinical training in otology.

Abstract:Objective To establish an in vitro model to study the interaction between induced M1-type macrophages and auditory nerve myelin Schwann cells.Methods Cochlear tissues from 7-day-old C57BL/6J mice were selected,and nerve fragments were digested to produce a mixed culture of Schwann cells and fibroblasts.Purified Schwann cells were obtained using differential adhesion and cytosine arabinoside treatment.Mouse bone marrow monocytes were polarized into M1 macrophages using macrophage colony-stimulating factor and lipopolysaccharide.The purified Schwann cells were then co-cultured with the induced M1 macrophages at a 1:1 cell ratio.Analysis was performed using immunofluorescence staining,cell counting,and enzyme-linked immunosorbent assay.Results The results showed a significant decrease in the number of Schwann cells on the third day after co-culture compared to the first day(P<0.001).There was a statistically significant difference in the secretion levels of brain-derived neurotrophic factor in the supernatant between the pure Schwann cell culture group and the co-culture group(P<0.001).Conclusions This study successfully established,a co-culture model of auditory nerve myelin Schwann cells and macrophages.This method holds significant value for in-depth research on the mechanism of macrophage influence on auditory nerve myelin Schwann cells and provides a foundation for understanding the immune response in the inner ear.

Abstract:Objective To report changes in inner ear MRI before and after virtual reality vestibular rehabilitation therapy in patients with sudden deafness with vertigo,as well as factors that can influence treatment outcomes.Methods Patients with sudden deafness accompanied by dizziness admitted to our hospital from April 2022 to August 2024(n=111)were divided into a control group(routine therapies,n=59)and a study group(virtual reality therapies,n=52)based on the vestibular rehabilitation therapy modality they chose,with 41 patients in each propensity score matching(PSM)group.Hospital Anxiety and Depression Scale(HADS)and Dizziness Handicap Inventory(DHI)scores,and the cochlea/medulla oblongata(CM)ratio on inner ear MRI were compared between the two groups and before and after treatment using ANOVA.Factors influencing treatment efficacy were analyzed using generalized estimation equations.Results After 7 and 14 days of treatment,all HADS scores were lower than before treatment in both groups(P<0.05).Therapy modality and time after treatment were main influencing factors on DHI-F,DHI-E,DHI-P and total DHI scores,and on the CM ratio(P<0.05).After 14 days of treatment,all DHI scores and the CM ratio in the study group were also lower compared with the control group(P<0.05).The CM ratio was correlated to DHI-F,DHI-E,DHI-P and total DHI scores(P<0.05).Age,disease course,CM ratio,severity of hearing loss and hearing loss pattern affected clinical outcomes in these patients(P<0.05).For predicting treatment outcomes,the ROC curve showed the highest Yodene index at 0.610 when the CM ratio was 2.20,with corresponding sensitivity and specificity at 0.806 and 0.804,respectively,and an area under the ROC curve of 0.848,indicating certain values of the CM ratio in predicting treatment efficacy for sudden deafness with vertigo.Conclusions Compared with conventional rehabilitation therapies,vestibular rehabilitation assisted by virtual reality can significantly improve vertigo symptom outcomes with better treatment efficacy in patients with sudden deafness and vertigo.It can significantly reduce the CM ratio,probably by improving function of the blood-labyrinth barrier,which can be used to predict clinical outcomes.

Abstract:Objective To identify consistent abnormal brain activity regions in tinnitus patients by resting state functional magnetic resonance imaging(rs-fMRI),and to elucidate neural mechanisms of brain injury and functional remodeling.Methods The literature on local consistency regional honogeneity(ReHo)and low-frequency amplitude(ALFF),fractional low-frequency amplitude(fALFF)indexes used to assess brain function changes in tinnitus patients published up to January 3,2024,was searched.After screening with the inclusion and exclusion criteria,the activation likelihood estimation method was used to extract information on the brain regions with abnormal spontaneous neural activity in tinnitus patients in selected studies.Results A total of 29 studies from 22 reports(746 cases of tinnitus and 653 cases of control)were included.Meta-analysis of ReHo,ALFF and fALFF data showed increased activity in the right middle temporal gyrus(MTG.R)in tinnitus patients compared with healthy controls,and no brain regions of decreased activities.Analysis of ReHo data element alone revealed increased activity in the left middle occipital gyrus(MOG.L)and left posterior cingulate(PCC.L),and decreased activities in the dorsolateral right superior frontal gyrus(SFGdor.R),left cerebellar anterior lobe(CAL.L).ALFF/fALFF data element analysis alone revealed no brain regions showing increased or decreased activities when compared to healthy controls.Conclusions ALE-Meta analysis confirms abnormal spontaneous activities involving multiple brain regions in patients with tinnitus,which may be helpful to understanding the neuropathological basis of functional brain injury and remodeling in tinnitus.

Abstract:Objective To report outcomes of endoscopic tympanoplasty with intraoperative steroids infusion in patients with chronic simple suppurative otitis media,including air-and bone-conduction thresholds,expression of inflammatory factors,pain,tinnitus,anxiety and depression.Methods Forty-five patients with chronic simple suppurative otitis media admitted to the First Affiliated Hospital of Bengbu Medical University from January 2023 to May 2024 were assigned to receive endoscopic tympanoplasty with built-in otocanal cartilage type I only(control group),with intraoperative dexamethasone infusion(dexamethasone group),or with budesonide infusion(budesonide group).Pre-and postoperative data including air-and bone-conduction thresholds,neutrophil-to-lymphocyte ratio,C-reactive protein,visual analogue scale,tinnitus handicap inventory-Chinese version,self-rating anxiety scale,and self-rating depression scale were collected.Statistical analysis was performed using the SPSS 27.0 software.Results All patients showed improvements in all indexes at 1 month,while patients receiving intraoperative dexamethasone or budesonide infusion outperformed the control group by several indexes(P<0.05)although not between themselves as measured by C-reactive protein,visual analogue score,tinnitus handicap inventory-Chinese version and self-rating depression scale scores(P>0.05).The budesonide group demonstrated better outcomes compared to the dexamethasone group(P<0.05),except for the air-conduction and bone-conduction thresholds,where no significant difference was found(P>0.05).The differences were no longer significant at 3 months(P>0.05).Conclusions Endoscopic tympanoplasty combined with intraoperative steroids infusion(particularly budesonide)can provided short-term outcome superiority in hearing improvement and control of inflammation,pain,tinnitus,anxiety and depression in patients with chronic simple suppurative otitis media compared to without.These findings may help plan clinical treatment strategies.

Abstract:Objective To investigate the value of combined audiological testing in diagnostic and prognostic evaluation in sudden deafness(SD).Methods A total of 298 patients(135 females and 163 males,average age=53.3±3.5 years)initially diagnosed with SD at Lianyungang Municipal Dongfang Hospital from January 2022 to March 2024 were underwent combined audiological testing including tympanometry,pure tone audiometry,otoacoustic emissions,and auditory brainstem responses.Patients suspected of retrocochlear lesions were referred for imaging evaluation.Results Tympanometry showed type A tympanograms in all 298 patients.Pure tone audiometry revealed sensorineural hearing loss.Otoacoustic emissions were abnormal in 283 cases.Auditory brainstem responses showed prolonged latencies of waves Ⅰ,Ⅲ and Ⅴ in 16 cases,with the Ⅰ-Ⅴ interpeak interval prolonged in 7 cases and the Ⅲ-Ⅴ interpeak interval prolonged in 9 cases.Magnetic resonance imaging revealed acoustic neuroma in 9 cases,large intracranial hemangioma in 2 cases,intracranial metastatic tumor in 2 cases,and cerebral focal infarction in 3 cases.The rate of complete hearing recovery was 72.9％(121/166)for low-frequency descending hearing loss SD and 57.9％for flat descending hearing loss.Hearing improvement was seen in 40.8％of the cases with high-frequency descending hearing loss.Inefficiency is 42.3％.Hearing was not significantly improved postoperative in the 9 patients with acoustic neuroma.Of the 2 patients with intracranial hemangioma,hearing improved in 1 case after surgery.Treatment was ineffective in terms of hearing in the 2 patients with intracranial metastatic tumors.Conclusions This study demonstrates that combined audiological testing is of great value in the diagnosis and treatment of SD,with a complimentary effect in identifying,locating and quantifying etiologies of hearing loss,as well as in differential diagnosis,thereby improving diagnostic accuracy and reliability,reducing misdiagnosis and missed diagnosis,and aiding in predicting disease outcomes and guiding personalized treatment.

Abstract:Objective With the development of the society,medicine and technology and prolongation of life expectancy,the problems associated with aging have become increasingly prominent.Hearing loss has emerged as a social issue that can seriously affects the quality of life in the elderly.Presbycusis,also known as age-related hearing loss,results from the combined action of multiple factors.To gain insights on pathogenesis and intervention measures of presbycusis,this article reviews related research from the following aspects:relevant mechanisms of aging,pathogenesis of presbycusis,and its treatment of presbycusis,by summarizing recent research findings.

Abstract:Objective To report the results of neonatal concurrent hearing and genetic screening conducted at Zigong Maternity and Child Health Care Hospital,including the rate of deafness genes carriers and hearing status of individuals with gene mutations,to provide a scientific basis for optimizing local strategies for the prevention and control of deafness.Methods Between May 2022 and July 2024,routine hearing screenings were conducted on 2,315 newborns,together with screening for mutations at 23 sites of the GJB2,GJB3,SLC26A4 and mitochondrial 12S rRNA genes.For newborns who failed the hearing screening,audiological diagnoses were completed within three months after birth.Results 557 newborns(24.1%)tested positive for pathogenic mutations,with GJB2 c.109 G>A(10.4%)showing the highest frequency among all genotypes,followed by GJB2 c.235 delC(1.1%)and SLC26A4 c.919-2A>G(0.6%).While 2,263(97.9%)passed both hearing and genetic screenings,30(1.3%)failed genetic screening,8(0.4%)failed hearing screening,and 11(0.5%)failed both.The 11 newborns failing both screenings all carried mutations in the GJB2 gene,with 10(90.9%)carrying the c.109G>A mutation.Audiological diagnosis confirmed,hearing loss in 4 newborns who failed the genetic screening,including 3 with homozygous c.109G>A mutation and 1 with compound heterozygous c.109G>A/c.235 del C mutation.Conclusions GJB2 c.109G>A is the most common deafness-associated mutation in Zigong.Carriers of homozygous or compound heterozygous mutations require long-term hearing follow-ups for early detection and intervention.

Abstract:Objective To investigate the expression regulation mechanism of pyroptosis-related proteins in an oxidative stress model of H2O2 induced HEI-OC1 cells,and the effects and mechanisms of disulfiram on pyroptosis-related signaling pathways.Methods HEI-OC1 cells were treated with H2O2 disulfiram or H2O2 combined with disulfiram,and cell viability was detected by cell counting kit-8.ROS generation in cells was detected using flow cytometry and immunofluorescence techniques.The expression of key proteins NLRP3,caspase-1,and N-GSDMD pyroptosis was detected by immunofluorescence.and mRNA expression levels of pyroptosis-related genes NLRP3,caspase-1,GSDMD,IL-1β,and IL-18 by RT-qPCR.Morphological changes of cells were examined by scanning electron microscopy.Levels of inflammatory factors IL-1β and IL-18 in cell culture supernatant were detected by ELISA.Results HEI-OC1 cells inhibitory concentration(IC50)after 4 h of H2O2 exposure was 829.5 μmol/L,and cell viability was observed at 5 μmol/L disulfiram,so 5 μmol/L disulfiram+800 μmol/L H2O2,ROS were significantly increased after treatment with H2O2(P<0.001),together with NLRP3 caspase-1,N-GSDMD protein expression(P<0.0001)and elevated levels of factors IL-1β,IL-18 in the cell culture supernatant(P<0.001),as well as mRNA expression levels of LRP3,caspase-1,GSDMD,IL-1β and IL-18(P<0.001).Scanning electron microscopy showed swollen cells with holes and a large number of vesicular protuberances.When treated with H2O2 combined with disulfiram,ROS generation was significantly lower(P<0.01),with significantly less expression of pyroptosis-related proteins(P<0.05),less mRNA expression of NLRP3,caspase-1,GSDMD,IL-1β,IL-18 were decreased(P<0.05),and less elevation of inflammatory factors IL-1β,IL-18 in the culture supernatant(P<0.01),with scanning electron microscopy showing less holes cells and less vesicular protuberances on cell membrane.Conclusions H2O2 can induce oxidative stress response and trigger cell pyroptosis in HEI-OC1 cells,and disulfiram can reduce H2O2-induced HEI-OC1 cell injury by inhibiting the generation of ROS and activation of NLRP3 inflammasome pathway.

Abstract:Objective To report cognitive function levels of patients with presbycusis and otitis media after surgical treatment as compared to those with presbycusis only,as well as factors affecting cognitive function improvement.Methods From September 2020 to March 2024,patients with presbycusis and otitis media(n=70)and patients with presbycusis only(n=70)pure underwent pure tone audiometry(PTA)and completed the Montreal Cognitive Assessment(MoCA)survey at Beijing Tsinghua Changgung Hospital,The differences between the two groups was analyzed using independent sample rank sum test.Tympanoplasty was performed on patients with otitis media.PTA,maximum speech discrimination scores(SDSmax),Tinnitus Disability Inventory(THI)scores,frequency of ear discharge and MoCA scores were completed before and 3 and 6 months after surgery.Independent/Paired sample rank sum test was used to compare preoperative and postoperative data in both groups.Spearman rank correlation test and multiple factor linear regression were used to identify factors influencing cognitive function improvement.Results The total MoCA score is lower in patients with presbycusis and otitis media[23.5(21,25)]than in those with presbycusis only[26(24,27)](P<0.05).In patients with presbycusis and otitis media,the total MoCA scores at 3 months[24(22,26)]and 6 months[25(23,27)]after tympanoplasty surgery were higher than before surgery[23.5(21,25)](P<0.05).An increase in the MoCA score at 3 and 6 months after surgery was associated with improvement in hearing and frequency of ear discharge(P<0.05).Conclusions Patients with presbycusis and otitis media may have more significant cognitive decline.Tympanoplasty may improve cognitive function in these patients by reducing or eliminating conductive hearing loss and ear discharge.

Abstract:Objective To report clinical outcomes of advanced external auditory canal adenoid cystic carcinoma(ACC),including causes of recurrence and management strategies.Methods Clinical data of 10 patients(4 males and 6 females)with ACC of the external auditory canal diagnosed at the General Hospital of the Chinese People's Liberation Army from January 2021 to December 2023 were retrospectively analyzed,including clinical manifestations,imaging characteristics,surgical strategies employed,postoperative follow-ups and outcomes.Results Disease duration ranged from 3 to 23 years.Initial clinical symptoms included earache(9 cases),external auditory canal mass(3 cases),hearing loss(3 cases)and otorrhea(2 cases).All cases had received local tumor resection at other hospitals.Based on the Pittsburgh classification,the lesion was T3 in 1 patient and T4 in 9.Four patients exhibited distant metastases,all in lungs.Six patients underwent subtotal or total temporal bone resection and subsequent radiotherapy and chemotherapy at local hospitals.The mean follow-up duration was(34.7±12.7)months,and the shortest recurrence time was 3 months.Nine patients survived with tumors,while 1 patient was tumor-free.Conclusions Local resection of external auditory canal tumor resulted in less favorable postoperative tumor control,with short-term local recurrence and poor prognosis.Both domestic and international guidelines for treating external auditory canal cancer state that the initial surgery is critical,emphasizing on complete or expanded tumor resection followed by radiotherapy and chemotherapy,supplemented when necessary with targeted therapy or immunotherapy to improve outcomes.

Abstract:Objective Previous studies have indicated that gastroesophageal reflux disease(GERD)is associated with hearing loss(HL)and tinnitus.This study aims to investigate the causal relationship between GERD and major types of HL,including idiopathic sudden sensorineural HL,sensorineural HL,mixed HL,conductive HL,and tinnitus,using a two-sample Mendelian randomization(MR)approach.Methods Single nucleotide polymorphisms(SNPs)strongly associated with GERD were used as instrumental variables.The SNP datasets for GERD,HL and tinnitus and non-tinnitus were downloaded from the European Bioinformatics Institute,the FinnGen database,and the UK Biobank,respectively.The inverse variance weighted(IVW)method,along with three other commonly used MR models,was employed for analysis.Sensitivity analyses were performed using Cochran's Q test,MR-Egger intercept test,leave-one-out analysis,funnel plot and Mendelian randomization pleiotropy residual sum and outlier(MR-PRESSO)tests.Results IVW analysis indicated that GERD increases the risk of idiopathic sudden sensorineural HL(OR:1.365,95%CI:1.079～1.726,P=0.009)and decreases the risk of non-tinnitus(OR:0.950,95%CI:0.927～0.974,P<0.001).Sensitivity analysis showed no heterogeneity,horizontal pleiotropy,or outliers among the SNPs included in the MR analysis.Conclusions GERD significantly increases the risk of idiopathic sudden sensorineural HL and tinnitus.This study provides a theoretical basis for the diagnosis and treatment of hearing loss and tinnitus.

Abstract:Objective To report post-traumatic growth in parents of children with congenital deafness who had received cochlear implants,as well as influencing factors.Methods Using the convenience sampling method,211 parents of children with congenital deafness who visited the First Affiliated Hospital of Anhui Medical University and the Second People's Hospital of Anhui Province from April to December 2023 were enrolled as the research subjects,including 24 fathers and 187 mothers,aged 22 to 65 years(average age=34.18±8.34 years).The subjects completed a general questionnaire,the post-traumatic growth scale,psychological resilience scale,social support scale,and coping style scale.Results The average post-traumatic growth score was 63.53±8.06 points.Multiple linear regression analysis showed that educational level,family per capita monthly income,marital status,psychological resilience,social support,and positive coping were influencing factors of post-traumatic growth(P<0.05).Conclusions Parents of children with congenital deafness who undergo cochlear implantation generally show a medium to low level of post-traumatic growth.Medical staff should pay special attention to parents with lower educational levels,poor family economic conditions,and are divorced.Through formulation of targeted intervention measures,improvement of psychological resilience and social support,and change of negative coping styles,their post-traumatic growth level can be improved.

Abstract:Vestibular migraine(VM)is a common clinical disorder characterized by recurrent vertigo attacks.Mechanisms related to abnormal glutamate(Glu)metabolism in astrocytes may trigger VM.Abnormal glutamate metabolism in astrocytes may involve factors including transporters,ion channels,neurotransmitters interactions and abnormal glutamate-glutamine cycle,which can lead to excitotoxicity and neuronal death,activate the thalamus,and cause central sensitization phenomenon,resulting in dysregulation of multimodal information integration and processing at the vestibular-thalamus-cortical level.This article provides a comprehensive exploration of the specific role of abnormal glutamate metabolism in astrocytes in the pathogenesis of VM,aiming to provide new potential targets for the treatment of VM.

Abstract:Objective To investigate the relationship between lipid metabolism markers and hearing difficulty in noise,as well as their roles in early stages of hearing loss.Methods Based on Mendelian randomization(MR)design,and using data from two large-scale genome-wide association study databases,i.e.the UK Biobank and the Global Lipids Genetic Consortium,associations between lipid metabolism indicators,such as high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),triglycerides,and speech recognition difficulties in noise were evaluated.The inverse-variance weighted method was employed as the primary analytical approach,and multivariable MR analysis was conducted to further validate the independent contribution of lipid metabolism markers.Results Two-sample MR analysis revealed a significant protective relationship between HDL-C and hearing difficulty in noise(UK Biobank dataset:OR=0.993,95%CI:0.987～0.999,P=0.014).This association remained robust in multivariable analysis(OR=0.992,95%CI:0.984～1.000,P=0.045).In contrast,other lipid metabolism markers did not demonstrate significant independent causal effects.Furthermore,while the protective effect of HDL-C in the Global Lipids Genetic Consortium dataset exhibited a similar trend,it did not reach statistical significance(OR=0.994,95%CI:0.987～1.000,P=0.054).Multivariable MR results also showed a marginal association(OR=0.992,95%CI:0.983～1.000,P=0.064).Conclusions HDL-C exhibits a protective role against hearing difficulty in noise.Improving HDL-C levels may positively impact hearing health by mechanisms such as suppressing inflammation,exerting antioxidant effects and improving microcirculation.