Abstract:Objective To report genetic mutation characteristics in children with hearing loss and provide a basis for preventing genetic hearing loss in Hainan region by we analyzing the carrier status of deafness-causing genes in 300 children with hearing loss in Hainan province,China.Methods Used high-throughput sequencing to detect 9 common hearing loss genes(COCH,GJB2,GJB3,GJB6,KCNQ4,POU3F4,MT-RNR1,SLC26A4 and TMIE)in children with hearing loss in Hainan region,from January to December 2023 aged 0～18 years,and analyzed their carrier status in these children.Results Among the 300 children,154 children(51.3%)were found to carry hearing loss genes,of whom,96(32.0%).had a definite genetic diagnosis(including homozygous,compound heterozygous and hemizygous mutations),and were heterozygous mutations in 58 cases(19.3%).Detected variants involved three genes,namely GJB2,SLC26A4 and POU3F4,respectively,with the GJB2 gene showing the highest total mutation rate at 45.0%and the main mutation form as c.109G>A.The main mutation form of SLC26A4 gene was c.919-2A>G.Two variants of the POU3F4 gene,i.e.c.530C>A hemizygous mutation and c.406C>T hemizygous mutation compound c.109G>A heterozygous mutation were detected.Conclusions The GJB2,SLC26A4 and POU3F4 genes are the most common pathogenic genes for genetic hearing loss in children in Hainan Province.The GJB2 c.109G>A mutation is a hotspot,and the carrier rate of POU3F4 mutations is relatively high in the Hainan population.Targeted genetic screening in newborns or during pregnancy may help reduce the incidence of deafness.

Abstract:Objective The aim of this study was to develop a method for cochlear scanning electron microscope(SEM)samples preparation without the use of highly toxic osmium tetroxide(OsO4)that imposes strict operational restrictions and safety risks.Methods The cochlea of normal hearing guinea pigs was fixed by 2.5%glutaraldehyde perfusion for 24 hours instead of the traditional OsO4 fixation.After decalcification with 10%EDTA for 3 days and microdissection to expose the basilar membrane,dehydration was completed by gradient ethanol and carbon dioxide critical point drying.Finally,by optimizing the multi-angle ion sputtering coating,a uniform 5-10nm conductive gold film was formed on the sample surface.Results There was no"osmium black"or structural deformation caused by OsO4 in the cochlea.The overall shape of the cochlea and the distribution of hair cells in each turn were clearly displayed at low power.The cilia bundles of inner and outer hair cells were arranged neatly and the microvilli of cuticular plate were visible at medium power.Conclusions The proposed method successfully overcame the defects in electrical conductivity and contrast ratio caused by OsO4 deficiency,with imaging resolutions comparable to that of conventional preparation with OsO4,especially clearly visible for sub-micron details of cilia(lateral links).By glutaraldehyde fixation combined with precise control of the sputtering process,this technology completely eliminates the safety and compliance barriers related to highly toxic reagents,significantly reduces experimental complexity and cost,and provides a safe,efficient and high-quality solution for the study of inner ear ultrastructure morphology that is generally suitable for most laboratories.

Abstract:Masseter vestibular evoked myogenic potentials(mVEMPs),as responses involving the auditory-masseter and vestibular-masseter reflex pathways,can be used as a complementary test to assess function of the vestibular trigeminal nerve pathway to help diagnose brain stem damage in REM sleep behavior disorders,multiple sclerosis,amyotrophic lateral sclerosis and Parkinson's disease.as a supplement to clinical and radiographic examinations,mVEMP has certain clinical values and can facilitate research.This article reviews its neural mechanisms and potential clinical applications.

Abstract:Perrault syndrome is a rare autosomal recessive disorder characterized by sensorineural hearing loss and ovarian dysfunction.Studies have shown that mutations in eight genes,including HARS2,CLPP,ERAL1,GGPS1,HSD17B4,LARS2,RMND1 and TWNK,are associated with this syndrome.In this review,we systematically review the structure,mutation types and pathogenic mechanisms of the HARS2 gene,and focus on the effects of mutations on protein stability,aminoacylation activity and mitochondrial function,in order to provide a theoretical basis for early diagnosis and targeted therapies of this syndrome.

Abstract:Lassa fever is an acute animal borne hemorrhagic fever caused by Lassa virus,and about one-third of survivors will experience sensorineural hearing loss.This article systematically reviews the research on Lassa virus and its mediated hearing loss,and elucidates that the mechanism of hearing loss may be related to immune response mediated loss of inner ear nerve cells.Further research is needed in the future to investigate the pathogenesis of Lassa virus mediated hearing loss,laying a foundation for the development of effective auditory rehabilitation strategies.

Abstract:Objective To report protective effects of diselenide cross-linked nano-loaded astaxanthin(AST@dSe-AFT)against cisplatin-induced inner ear hair cell injury.Methods HEI-OC1 hair cells were treated with cisplatin,cisplatin+AST@dSe-AFT or cisplatin+AST.To assess protective effects on hair cells by AST@dSe-AFT,the cell counting kit-8 was used for cell viability,DCFH-DA for reactive oxygen species and Rhodamine123,Mito Tracker Red CMXRos for mitochondrial membrane potentials and immunofluorescence,Western Blot and qPCR for expression of autophagy related proteins.C57BL/6 mice were randomly selected to receive cisplatin,cisplatin+AST or cisplatin+AST@dSe-AFT.Hearing was evaluated by auditory brainstem responses(ABRs)and cochlear basement membrane hair cells by immunofluorescence staining for protection by AST@dSe-AFT against hair cell damage by cisplatin.Results In vitro experiments,treatment with AST@dSe-AFT led to reduced accumulation of reactive oxygen species in cells,with increased mitochondrial membrane potentials and decreased expression of autophagy related proteins and genes induced by cisplatin.In vivo AST@dSe-AFT treatment yielded alleviated cochlear hair cell damage and hearing loss caused by cisplatin.Conclusion Both in vitro and in vivo results confirm that AST@dSe-AFT can effectively protect against cisplatin-induced ototoxicity.

Abstract:Objective To investigate the correlation between LINC01224,miR-193a-5p,and ELMOD3 c.512A>G mutations and sensorineural hearing loss(SNHL),as well as the significance of their clinical screening by analyzing their expression profiles in peripheral blood in patients with SNHL.Methods Potential miRNAs regulating ELMOD3 were predicted using TargetScan,RNAInter and miRDB databases,followed by Venn diagram intersection analysis.The starBase database was employed to predict lncRNA/miRNA-ELMOD3 regulatory networks.Dual-luciferase reporter assays were conducted to validate targeting interactions among predicted lncRNAs,miRNAs,and ELMOD3.A cohort of 24 patients with SNHL diagnosed at the Department of Otolaryngology-Head and Neck Surgery,Eighth Affiliated Hospital of Sun Yat-Sen University from January 2023 to January 2024 and 12 normal-hearing volunteers were enrolled.SYBR Green-based RT-qPCR was performed to quantify LINC01224 and miR-193a-5p expression in peripheral blood,while Sanger sequencing screened for the ELMOD3 c.512A>G mutation.Relative expression levels were calculated using the 2-ΔΔCt method,followed by statistical analysis.Results Integrated database analysis identified 31 high-confidence miRNAs targeting ELMOD3.LINC01224 and miR-193a-5p were selected as core molecules based on starBase predictions and prior evidence.Dual-luciferase assays confirmed direct targeting between LINC01224/ELMOD3 and miR-193a-5p.LINC01224 expression was significantly upregulated in the SNHL group compared to controls(P<0.0001),whereas miR-193a-5p was downregulated(P<0.0001).The ELMOD3 c.512A>G mutation was undetected in both groups.Conclusion Bioinformatic predictions suggest LINC01224 and miR-193a-5p as upstream regulators of ELMOD3.The significant differential expression of LINC01224(↑)and miR-193a-5p(↓)in SNHL patients highlights their potential association with disease pathogenesis and warrants further investigation as diagnostic serum biomarkers.The absence of ELMOD3 c.512A>G mutations in this cohort necessitates expanded sample sizes and whole-exon sequencing of ELMOD3 to identify novel pathogenic variants and validate its role as a hotspot gene/locus in SNHL.

Abstract:Functional near-infrared spectroscopy(fNIRS),as a non-invasive,safe and portable neuroimaging technique,plays a pivotal role in investigating cerebral cortex activity in cochlear implant(CI)patients.This article systematically summarizes the advantages and limitations of fNIRS technology along with its extensive applications across various disciplines,particularly emphasizing its utilization in cross-modal reorganization studies of auditory cortex in CI patients.Furthermore,the summary comprehensively examines current research progress regarding fNIRS applications in evaluating linguistic cognitive abilities,elucidating speech development mechanisms,and predicting postoperative rehabilitation outcomes in CI patients.

Abstract:Objective To compare clinical practicability between the Tinnitus Evaluation Questionnaire(TEQ)and the Chinese version of the Tinnitus Handicap Inventory(THI-C).Methods Patients with tinnitus as the primary complaint(n=283)seen at the Department of Otorhinolaryngology,Head and Neck Surgery of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine(GZUTCM)from January to December 2023 were assessed of the severity of their tinnitus using the THI-C and TEQ their initial visit,both by the patients themselves and by medical staff.The assessment was repeated at each follow-up visit,and the time spent on the assessment was recorded.The operability was assessed by the rate of completion in both self-and medical assessments as well as the assessment time,and the reliability was examined by the consistency between self-and medical assessments.The effect size(ES)and minimal clinically important difference(MCID)were calculated to determine their feasibility in outcomes evaluation.Results The rate of THI-C self-assessment completion was 42.76%at the first visit(92.23%for medical evaluation),and 40.83%～53.97%at the second to sixth visits.The rate of TEQ self-evaluation completion was 97.88%at the initial visit,(100%for medical assessment at the first visit and each follow-up visit).The time needed for THI-C self-evaluation(3.90±2.44 min)was significantly lower than medical evaluation(8.09±1.77 min)(P<0.001),while that for TEQ self-evaluation(1.84±1.09 min)was slightly higher than medical evaluation(1.31±0.49 min)(P<0.001).The score of THI-C self-evaluation(47.95±26.14)was significantly higher than medical evaluation(39.21±21.45)(P<0.001),and the difference was less than 8 points in only 46 cases(16.25%).The TEQ self-score(12.69±3.53)was also slightly higher than medical evaluation(12.14±3.08)(P<0.001),with the difference being less than 2 points in 173 cases(61.13%).The ES was 0.159 and 0.854 for patients showing improvement or significant improvement as measured by the THI-C,respectively,and 0.197,1.005 and 1.883 for patients showing no change,improvement or significant improvement as measured by the TEQ,respectively.The MCID was 19 by subjective calibration and 13 by 1/2 standard deviation when calculated using the THI-C,and 2 by both methods when using the TEQ,respectively.Conclusion THI-C is less practical in clinical evaluation as routine self-evaluation,whereas TEQ is feasible and reliable in routine medical evaluation,and can be used for outcomes evaluation.

Abstract:Objective To report effects of chitosan-Prussian blue nanomases(CS-PB)on oxidative stress injury of HEI-OC1 cells induced by H2O2 and related molecular mechanisms.Methods HEI-OC1 cells were cultured and oxidative stress injury established by treatment with H2O2 of various concentration gradients and measurement of intracellular cell counting kit-8 activity.Based on the treatment,these cells were divided into the control,H2O2 treatment,H2O2+CS-PB and H2O2+N-Acetylcysteine groups.Intracellular ROS content was detected by DCFH-DA fluorescence probe technology;intracellular expression levels of Bcl-XL,Bax,TNF-α and IL-1β proteins by Western blot;and content of 4-HNE by immunofluorescence staining and confocal laser microscopy.Results Compared with the control,cell viability and Bcl-XL protein expression in H2O2 treatment cells were decreased(P<0.0001),with increased intracellular reactive oxygen species,4-HNE,TNF-α,IL1β and Bax expression(P<0.0001).Compared with the H2O2 treatment only group,cell viability and Bcl-XL protein expression in H2O2+CS-PB and H2O2+NAC groups were higher(P<0.05),with lower intracellular ROS,4-HNE,TNF-α,IL-1β and Bax expression(P<0.01).Conclusion CS-PB can alleviate cell damage and apoptosis caused by hydrogen peroxide induced oxidative stress in HEI-OC1 cells.

Abstract:Objective The purpose of this study was to determine the benefits of binaural-bimodal fitting combining a cochlear implant and a contralateral hearing aid in patients with unilateral cochlear implant.Methods Unilaterally cochlear implanted patients with binaural-bimodal fitting(n=54)received pure tone tests in sound field in three modes:CI only,HA only and BIM combining the cochlear implant and a contralateral hearing aid.Speech recognition tests included monosyllabic words,disyllabic words,short sentence recognition rate in quiet and speech recognition in noise.Results There was a significant difference in pure tone average(PTA)between CI mode and BIM mode(P=0.006).Recognition of monosyllabic words,disyllabic words and short sentence in quiet was better in BIM mode than in CI only mode(P<0.01),with less loss of signal-to-noise ratio(P<0.01).Conclusion Binaural-bimodal fitting has certain advantages in auditory and speech recognition ability in patients with unilateral cochlear implant.

Abstract:Objective To report a method for detection of cortical auditory evoked potential(CAEP)and characteristics of P1-N1-P2 waveforms in miniature pigs.Methods P1-N1-P2 waveforms were recorded in male miniature pigs with normal hearing(n=4)using tone bursts under anesthesia,including P1-N1-P2 latencies and amplitudes.Results P1-N1-P2 waves were detected in all 4(8-ears)animals(100%).The latency was 45.13±14.07 ms for P1,(96.00±10.72)ms for N1,and(135.13±13.95)ms for P2,while the amplitude was(2.21±1.04)μV for P1-N1,and(1.37±0.37)μV for N1-P2.Conclusion P1-N1-P2 waves reflect the auditory cortex function in miniature pigs and are similar to those in humans.Miniature pigs can be an animal model for studying auditory cortex function.

Abstract:Weighted sound pressure level measures are widely used and play an important role in various fields including biomedicine,environmental monitoring,music production,and acoustic engineering.They involve weighted filtering on environmental noises according to the test objects and the test goals.Weighting can not only simulate the auditory characteristics of human beings but also meet the application requirements in acoustic engineering.It includes A,B,C,D and Z weighting curves,with B and D weightings no longer in use.A weighting is widely used in the measurement of background noise in audiometric rooms.We proposed to apply weighting to the measurement of background noise in the sound-insulated shielding room for animal experiments.In the design of hearing aids,application of weighting can not only improve users'hearing but also protect them from noise interference.Protective headphones can not only block damaging noise but also achieve the purpose of protecting hearing.This article also elaborates on the future trends in the development of weighting,future application of weighting technologies in combination with AI,and interprets the important value of weighting in optimizing sound perception and signal quality.

Abstract:Objective To report gait parameters during walking and their relationship with fear of falling in patients with acute vestibular neuritis.Methods We recruited 30 patients diagnosed with acute vestibular neuritis treated at the Department of Neurology,Xi'an No.3 Hospital Affiliated to Northwestern University,between November 2023 and January 2025 and 30 healthy family members of these patients as the control group.Gait parameters were measured during a 2-minute free walk,a single-task 12-meter walk,and a dual-task 12-meter walk(including serial 100-7 subtraction,naming and word recall).The Falls Efficacy Scale-International(FES-I)was used to assess the patients'fear of falling.We analyzed the correlation between gait characteristics under different walking conditions and fear of falling.Results Compared to the healthy control group,patients exhibited a significant reduction in stride length,gait velocity,and stride length during the 2-minute free walk(P<0.001),decreased Cadence(P=0.002),increased stance phase ratio,and reduced swing phase ratio(P<0.05).Compared to single task walking,patients demonstrated decreased Cadence(F=8.781,P<0.001),reduced gait velocity(F=8.443,P<0.001),decreased ground impact force(F=5.745,P<0.05),and prolonged gait cycle(F=7.681,P<0.001)during dual-task walking.There was a strong negative correlation between gait velocity,stride length,and swing phase ratio and the FES-I score during the 2-minute free walk(r=-0.714,-0.666 and-0.667,respectively,P<0.01),and a strong positive correlation between stance phase ratio and the FES-I score(r=0.658,P<0.01).Conclusion Patients with acute vestibular neuritis exhibit shorter stride lengths,slower walking speeds,and reduced step frequencies,along with an increased stance phase ratio.The impact of dual-tasking varies depending on the type of task,and fear of falling further diminishes walking ability in these patients.

Abstract:Cholesteatoma is a non-neoplastic cystic lesion located in the middle ear that can lead to deafness.It is characterized by abnormal growth of keratinized squamous epithelium,leading to erosion of structures in the middle ear space and adjacent bones.This condition can lead to various serious complications.Currently,cholesteatoma is routinely treated with surgery.However,the high recurrence rate after surgery significantly impacts patients'quality of life.Moreover,the challenges and risks associated with revision surgery are significant.Consequently,preventive strategies for this condition are needed to reduce ear-related morbidity.In this review,we examined the most recent literature to summarize risk factors and prevention strategies for recurrence after surgical treatment of cholesteatoma.The aim is to reduce the recurrence of cholesteatoma in clinical settings and provide evidence to improve the effectiveness of cholesteatoma surgery.

Abstract:With in-depth research on bone conduction mechanisms and technological innovations,application of bone conduction hearing aids and auditory implants has expanded significantly,offering more options for patients with hearing impairments.Studies indicate that mechanisms of sound transmission via bone conduction vary across frequencies.This article reviews five widely accepted hypotheses in bone conduction:intracanal sound pressure,ossicular inertia,cochlear fluid inertia,cochlear compression/expansion,and cerebrospinal fluid pressure transmission.It discusses the impact of bone conduction implants on sound source localization and tinnitus and summarizes the classification and characteristics of bone conduction and middle ear implant devices,aiming to provide basis for selecting suitable auditory implants in the clinic.

Abstract:Vestibular evoked myogenic potentials refer to myogenic action potentials recorded in superficial skeletal muscles of the body through specific reflex pathways in response to high-intensity sound,vibration or direct current stimulation of the utricle or saccule.Depending on the recording site,they can be divided into cervical,ocular and masseter vestibular evoked myogenic potentials.The two common clinical vestibular myogenic potentials are the cervical and oculomotor vestibular evoked myogenic potentials,recorded by stimulating the saccule or utricle on the same side of the sternocleidomastoid muscle or on the opposite side of the inferior oblique muscle.Both are widely used in the diagnosis of diseases related to the vestibular pathway.Stimulation includes air-conduction sounds,bone-conduction vibration and direct current stimulation,with the former two most commonly performed.Direct current stimulation is performed using a body surface electrode placed on the mastoid process to transmit electrical signals to the vestibular labyrinth and extracranial nerves.As a safe and reliable method of neuroelectric stimulation,it has been used in the study of pathologies such as vestibular disease and vestibular migraine,as well as vestibular physiology.Direct current stimulation is used to observe its effect on vestibular lesions and to study the function of the vestibular nerve.Direct current stimulation directly stimulating the afferent vestibule nerve is not yet a mature clinical research method.This study reviews the basis and existing academic research on direct current stimulation and vestibular evoked potentials.

Abstract:Objective The purpose of screening 14 153 newborns in Tengzhou city was to understand the distribution and sites of deaf gene mutations in this region and provide a basis for the diagnosis and treatment of hereditary deafness,genetic consultation and maternity guidance.Methods Using high-throughput sequencing methods,100 mutant sites of 18 deafness genes were screened among 14 153 newborns at Tengzhou Maternal and Child Health Hospital(Tengzhou Children's Hospital)from October 2018 to June 2022.Mutant sites and distribution of deaf gene mutations were analyzed.Results Among the 14 153 newborns,gene mutations were detected in 984(6.95％),with 27 carrying two types of mutation genes simultaneously.GJB2 gene mutations were detected in 421(2.97％),SLC26A4 gene mutations in 371(2.62％),GJB3 gene mutations in 72(0.51％),MT-CO1 gene mutations in 75(0.53％),and MT-RNR1 gene mutations in 30(0.21％).Conclusion Deafness genes mutations among newborn in Tengzhou area primarily involve the GJB2,SLC26A4,GJB3,MT-CO1 and MT-RNR1 genes.However,the pathogenity of the MT-CO1 gene m.7444G>A site has been downgraded.so probably not a target site of conventional testing.Neonatal deafness gene screening is of great significance for early diagnosis of hereditary deafness.The pathogenicity of mutations may change overtime,and genetic counseling should be considered both before and after testing.

Abstract:Objective To investigate the association between clinical symptoms and vestibular function at different stages of Ménière's disease(MD).Methods Data from patients with MD(n=187)diagnosed at the Vertigo Specialty Clinic of Yantai Yeda Hospital between June 2020 and October 2022 were retrospectively analyzed.Based on hearing thresholds,MD was classified StageⅠ(n=18),Ⅱ(n=30),Ⅲ(n=97)or Ⅳ(n=42).Clinical data,symptoms and vestibular test results were reviewed and compared.Results Age and affected side showed significant differences for the four disease stages(P<0.05),together with significant differences in subjective hearing loss,photophobia,motion sickness,sleep disturbances,hypertension,hyperglycemia and hyperlipidemia(P<0.05),as well as in vHIT(gain+saccades)and vHIT(saccades)results(P<0.05).Conclusion The rate of abnormal video head impulse test(vHIT)is positively correlated with MD staging,and increases with disease progression.Saccade parameters may serve as important indicators in MD diagnosis.

Abstract:Sudden deafness or sudden sensorineural hearing loss(SSNHL)is a common disease in otolaryngology,which can seriously impacts people's life and health.Its cause and pathogenesis remains unclear,but high plasma homocysteine(hHcy)and low folate levels have been reported to be associated with vascular injury and have recently been regarded as independent risk factors.Animal studies showed that folic acid can improve blood supply to the inner ear in mice with homocysteinemia.However,the pathogenesis and correlation between folic acid and deafness remain poorly understood.Enzymes that play a key role in folic acid metabolism mainly include MTHFR,MTR,MTRR,etc.The interaction between these nutrients related to folic acid metabolism and environmental factors may be related to SSNHL.There have been few studies on the relationship between folate deficiency and hearing loss,and the evidence on vascular etiology in SSNHL-related literature is often contradictory.This article aims to provide a review of the relevant research.