Objective:To explore the trend of hearing changes in infants with GJB2 gene p.V37I mutation at different months. Methods:The subjects were 54 children（108 ears） with p.V37I homozygous or compound heterozygous mutation in GJB2 gene. All the subjects underwent auditory brainstem response, auditory steady-state response, acoustic immittance and other audiological tests. Children were divided into three groups according to their age, 26 cases in group A were ≤3 months old, 17 cases in group B were>3~≤6 months old, and 11 cases in group C were>6 months old. Statistical analysis was performed on the three groups of ABR response threshold, hearing degree, the ASSR average response threshold of four frequencies and the ASSR response thresholds for each frequency of 500, 1 000, 2 000 and 4 000 Hz. Results:Among the 54 cases, 35 were male and 19 were female, with an age rang of 2-27 months and a median age of 4 months. The ABR response threshold of the three groups were ranked from low to high as group A, group B and group C, and the difference was statistically significant（P<0.05）. The ABR response thresholds of the three groups were ranked from low to high as group A, group B, and group C. The comparison between groups showed that the ABR response thresholds of group C was higher than that of group A（P=0.006）. The proportion of confirmed hearing loss in the three groups was 34.61%, 50.00% and 63.64%, respectively, and the difference of hearing level among the three groups was statistically significant（P<0.05）. The comparison between groups showed that the difference between group A and group C was statistically significant（P=0.012）, normal hearing accounted for the highest proportion in group A（65.39%）, while mild hearing loss accounted for the highest proportion in group C（45.46%）. The ASSR average response thresholds of the four frequencies in the three groups were ranked from low to high as group A, group B and group C, and the difference is statistically significant（P<0.05）. The comparison between groups showed that response ASSR thresholds of group C was higher than that of group A（P=0.002）. Response thresholds of ASSR in each frequency in the three groups were all ranked from low to high as in group A, group B and group C, and the differences were statistically significant（P<0.05）. Compared with each other between groups, response ASSR thresholds of group C was higher than those of group A（P=0.003） and group B（P=0.015） at 500 Hz, while response ASSR thresholds of group C was higher than group A at 1 000 Hz（P=0.010） and 2 000 Hz（P<0.001）, and there was no statistical difference at 4 000 Hz. Conclusion:The incidence of hearing loss in GJB2 gene p.V37I mutation increased with age, and the degree of hearing loss increased, the hearing progression was mainly 500, 1 000 and 2 000 Hz suggesting regular follow-up and alert to hearing changes.
Humans ; Connexin 26 ; Male ; Female ; Infant ; Child, Preschool ; Mutation ; Evoked Potentials, Auditory, Brain Stem ; Connexins/genetics* ; Auditory Threshold ; Hearing/genetics* ; Hearing Loss/genetics*

Objective:This study aims to investigate the mechanism and potential effects of two exposures to 100 dB sound pressure level（SPL） broadband white noise, with a 14-days interval, on the myelin sheath of the cochlear auditory nerve in mice. The research provides experimental evidence for understanding the pathophysiological processes of noise-induced hearing loss and hidden hearing loss. Methods:Fifteen 6-week-old male C57BL/6J mice with normal hearing thresholds were randomly divided into three groups: a control group（no noise exposure）, a single noise exposure group, and a double noise exposure group. The single noise exposure group was exposed to 100 dB SPL white noise for 2 hours, and ABR thresholds were measured 1 day（P1） and 14 days（P14） after the exposure. The double noise exposure group was exposed to the same conditions of 100 dB SPL white noise for 2 hours, followed by a second identical exposure 14 days later. ABR thresholds were measured 1 day（P15） and 14 days（P28） after the second exposure. The cochleae of all three groups were then collected for immunofluorescence observation of the basilar membrane and transmission electron microscopy to observe changes in the structure of the auditory nerve myelin sheath. Results:In the single noise exposure group, ABR thresholds at all frequencies were significantly elevated compared to the control group at P1. There were no significant changes in ABR thresholds at any frequency at P14. In the double noise exposure group, ABR thresholds at all frequencies were significantly elevated compared to the control group at P15 and P28（P<0.001）. After the first noise exposure, immunofluorescence observation revealed no significant weakening of the auditory nerve myelin sheath signal; transmission electron microscopy showed no significant changes in myelin sheath morphology. However, after the second noise exposure, immunofluorescence observation revealed a weakening of the myelin sheath signal, and transmission electron microscopy showed thinning of the myelin sheath, disruption of the lamellar structure, and separation from the axon, indicating demyelination. Conclusion:Two exposures to 100 dB SPL broadband white noise can lead to damage to the auditory nerve myelin sheath in mice, whereas a single exposure does not cause significant changes.
Animals ; Male ; Myelin Sheath/pathology* ; Mice ; Cochlear Nerve/pathology* ; Mice, Inbred C57BL ; Noise/adverse effects* ; Hearing Loss, Noise-Induced/physiopathology* ; Cochlea ; Evoked Potentials, Auditory, Brain Stem

Objective:X-linked non-syndromic hearing loss is an extremely rare type of hearing impairment. This study conducted a phenotypic and genetic analysis of a family with X-linked dominant inheritance to explore the causes of hearing loss. Methods:Clinical data were collected from a patient with non-syndromic hearing loss who visited the Otorhinolaryngology Department of the First Affiliated Hospital of Zhengzhou University in June 2023. Phenotypic and genetic analyses were performed on family members, including audiometric tests, whole-exome sequencing, and PCR-Sanger sequencing verification. Audiological assessments comprised pure-tone audiometry, impedance audiometry, auditory brainstem response, and otoacoustic emission tests. Results:The affected individuals in this pedigree have X-linked dominant non-syndromic deafness caused by mutations in the SMPX gene. The proband, along with their mother and maternal grandmother, exhibit varying degrees of sensorineural hearing loss. Whole-exome sequencing revealed a novel pathogenic variant, NM_014332.3: c. 133-2A>C, in the SMPX gene in the proband. Sanger sequencing confirmed that the proband, proband's mother, and grandmother all carried this pathogenic variant. Conclusion:This study reports a novel pathogenic variant in the SMPX gene, providing additional medical evidence for the diagnosis and treatment of X-linked dominant inherited non-syndromic hearing loss. It enriches the mutation spectrum of the SMPX gene.
Humans ; Pedigree ; Mutation ; Phenotype ; Male ; Hearing Loss, Sensorineural/genetics* ; Exome Sequencing ; Female ; Adult ; Hearing Loss/genetics* ; Evoked Potentials, Auditory, Brain Stem ; Muscle Proteins

Objective:To investigate the impact of Waardenburg syndrome（WS） -associated Sox10 p.S100Rfs*9 mutation on inner ear function and its mechanism in noise-induced hearing impairment. Methods:A mice model carrying the Sox10 p.S100Rfs*9 mutation was established using CRISPR-Cas9 gene editing technology. Auditory phenotypes were assessed under baseline conditions and after noise exposure（96 dB SPL, 2 hours）. Auditory brainstem response（ABR） tests were performed to evaluate hearing function, combined with immunofluorescence staining of cochlear basilar membrane whole-mounts to observe hair cells and ribbon synapses. Transcriptome sequencing was conducted to analyze molecular mechanisms. Results:Sox10 p.S100Rfs*9 heterozygous mice exhibited normal hearing thresholds with characteristic ventral pigmentation abnormalities under baseline conditions. Following noise exposure, mutant mice showed significantly higher ABR thresholds at 24 000 Hz compared to wild-type controls（[60.00±6.12]vs[48.13±4.28]dB SPL, P<0.000 1）, and a significant reduction in ribbon synapses（CtBP2-positive puncta） in the basal turn（[55.0±2.3]vs[64.8±3.3]per inner hair cell, P=0.006 6）, while hair cell morphology and number remained intact. Transcriptome analysis revealed altered expression of genes involved in immune regulation, membrane structures, ion channels, and neuroactive ligand-receptor interactions. Conclusion:The Sox10 p.S100Rfs*9 mutation does not alter baseline hearing function but significantly increases inner ear susceptibility to noise damage, primarily manifested as enhanced ribbon synapse vulnerability, especially in high-frequency regions. This gene-environment interaction reveals that Sox10 haploinsufficiency may compromise noise tolerance by affecting synaptic stability and inner ear protective mechanisms. These findings provide new perspectives on the phenotypic heterogeneity in WS patients and theoretical basis for individualized noise protection strategies for patients carrying SOX10 mutations.
Animals ; SOXE Transcription Factors/genetics* ; Waardenburg Syndrome/physiopathology* ; Mice ; Hearing Loss, Noise-Induced/genetics* ; Evoked Potentials, Auditory, Brain Stem ; Mutation ; Noise ; Disease Models, Animal ; Ear, Inner/physiopathology*

Noise-induced hearing loss is a worldwide public health issue that is characterized by temporary or permanent changes in hearing sensitivity. This condition is closely linked to inflammatory responses, and interventions targeting the inflammatory gene tumor necrosis factor-alpha (TNFα) are known to mitigate cochlear noise damage. TNFα-induced proteins (TNFAIPs) are a family of translucent acidic proteins, and TNFAIP6 has a notable association with inflammatory responses. To date, there have been few reports on TNFAIP6 levels in the inner ear. To elucidate the precise mechanism, we generated transgenic mouse models with conditional knockout of Tnfaip6 (Tnfaip6 cKO). Evaluation of hair cell morphology and function revealed no significant differences in hair cell numbers or ribbon synapses between Tnfaip6 cKO and wild-type mice. Moreover, there were no notable variations in hair cell numbers or hearing function in noisy environments. Our results indicate that Tnfaip6 does not have a substantial impact on the auditory system.
Animals ; Mice, Knockout ; Hair Cells, Auditory, Inner/pathology* ; Mice ; Mice, Transgenic ; Hearing Loss, Noise-Induced ; Evoked Potentials, Auditory, Brain Stem/physiology*

Objective:This study aims to analyze the threshold changes in distortion product otoacoustic emissions（DPOAE） and auditory brainstem response（ABR） in adult Otof-/- mice before and after gene therapy, evaluating its effectiveness and exploring methods for assessing hearing recovery post-treatment. Methods:At the age of 4 weeks, adult Otof-/- mice received an inner ear injection of a therapeutic agent containing intein-mediated recombination of the OTOF gene, delivered via dual AAV vectors through the round window membrane（RWM）. Immunofluorescence staining assessed the proportion of inner ear hair cells with restored otoferlin expression and the number of synapses.Statistical analysis was performed to compare the DPOAE and ABR thresholds before and after the treatment. Results:AAV-PHP. eB demonstrates high transduction efficiency in inner ear hair cells. The therapeutic regimen corrected hearing loss in adult Otof-/- mice without impacting auditory function in wild-type mice. The changes in DPOAE and ABR thresholds after gene therapy are significantly correlated at 16 kHz. Post-treatment,a slight increase in DPOAE was observeds,followed by a recovery trend at 2 months post-treatment. Conclusion:Gene therapy significantly restored hearing in adult Otof-/- mice, though the surgical delivery may cause transient hearing damage. Precise and gentle surgical techniques are essential to maximize gene therapy's efficacy.
Mice ; Animals ; Otoacoustic Emissions, Spontaneous/physiology* ; Hearing/physiology* ; Ear, Inner ; Hearing Loss/therapy* ; Genetic Therapy ; Auditory Threshold/physiology* ; Evoked Potentials, Auditory, Brain Stem/physiology* ; Membrane Proteins

Objective:To investigate the application value of NB CE-Chirp ASSR in the assessment of hearing threshold in children with hearing impairment. Methods:The hearing test results of 44 children with sensorineural hearing loss（88 ears） diagnosed in Shanghai Children's Hospital from January 2023 to December 2023 were retrospectively studied, including 19 ears in mild hearing loss group, 26 ears in moderate group, 20 ears in severe group and 23 ears in extremely severe group. Correlations between auditory brainstem response（ABR） thresholds, pure tone audiometry（PTA） thresholds and NB CE-Chirp ASSR response thresholds in different hearing loss groups were analyzed. Results:The threshold difference between ABR and NB CE-Chirp ASSR（2 000-4 000 Hz） was between 0.50-4.08 dB in different degrees of hearing loss group. There was a significant correlation between NB CE-Chirp ASSR and ABR response threshold in each group（P<0.001）, and the correlation coefficients of mild, severe and extremely severe groups were all greater than 0.8, showing a strong correlation. The average threshold difference between PTA and NB CE-Chirp ASSR in each group was between 1.88-3.91 dB. The correlation coefficients were all greater than 0.8, showing a strong correlation. The difference between PTA and NB CE-Chirp ASSR response threshold at 500, 1 000, 2 000 and 4 000 Hz in each groupwas between 0.25-3.84 dB. With the increase of frequency, the correlation coefficient between PTA and NB CE-Chirp ASSR response threshold showed an upward trend. The frequency with the highest coefficient was 4 000 Hz, and the r values were all greater than 0.9, followed by 2 000 Hz, and the correlation coefficient was relatively low at 500 Hz. In the extremely severe group, each frequency coefficient was greater than 0.7, showing a strong correlation. Conclusion:NB CE-Chirp ASSR has good frequency specificity and can reliably assess hearing thresholds in hearing-impaired children.
Humans ; Auditory Threshold ; Child ; Retrospective Studies ; Female ; Male ; Audiometry, Pure-Tone/methods* ; Evoked Potentials, Auditory, Brain Stem ; Child, Preschool ; Hearing Loss, Sensorineural/physiopathology* ; Adolescent

Objective: To investigate the application of cochlear nerve action potential (CNAP) monitoring in the resection of vestibular schwannoma, especially evaluating its significance for hearing preservation. Methods: From April 2018 to December 2021, 54 patients with vestibular schwannoma who underwent resection via retrosigmoid approach were collected in Chinese PLA General Hospital. Before surgery, all patients had effective hearing (AAO-HNS grade C or above). Brainstem auditory evoked potential (BAEP) combined with CNAP monitoring was performed during surgery. The CNAP monitoring was combined with continuous monitoring and cochlear nerve mapping. And patients were divided into hearing preservation group and non-preserved group according to postoperative AAO-HNS grade. SPSS 23.0 software was used to analyze the differences of CNAP and BEAP parameters between the two groups. Results: A total of 54 patients completed intraoperative monitoring and data collection, including 25 males (46.3%) and 29 females (53.7%), aged 27-71 years with an average age of 46.2 years. The maximum tumor diameter were (18.1±5.9) mm (range 10-34 mm). All tumors were totally removed with preserved facial nerve function (House-Brackmann grade I-II). The hearing preservation rate of 54 patients was 51.9% (28/54). During surgery, the V wave extraction rate of BAEP waveform was 85.2% (46/54) before tumor resection, 71.4% (20/28) in the hearing preservation group after tumor resection, and disappeared in the hearing preservation group (0/26). CNAP waveform was elicited in 54 patients during operation. Differences were found in the distribution of CNAP waveforms after tumor resection. The waveforms of the hearing-preserving group were triphasic and biphasic, while those in the non-preserving group were low-level and positive. For hearing preservation group, the amplitude of N1 wave after tumor resection was significantly higher than that before tumor resection[14.45(7.54, 33.85)μV vs 9.13(4.88, 23.35)μV, P=0.022]; However, for the non-preserved group, the amplitude of N1 wave after tumor resection was significantly lower than that before tumor resection [3.07(1.96, 4.60)μV vs 6.55(4.54, 9.71)μV, P=0.007]; After tumor resection, the amplitude was significantly higher than that of the unreserved group [14.45(7.54, 33.85)μV vs 3.07(1.96, 4.60)μV, P<0.001]. Conclusions: BAEP combined with CNAP monitoring is conducive to intraoperative hearing protection, and the application of cochlear nerve mapping can prompt the surgeon to avoid nerve injury. The waveform and N1 amplitude of CNAP after tumor resection have a certain value in predicting postoperative hearing preservation status.
Female ; Male ; Humans ; Middle Aged ; Neuroma, Acoustic/surgery* ; Action Potentials ; Evoked Potentials, Auditory, Brain Stem ; Cochlea ; Cochlear Nerve

Humans ; Auditory Pathways ; Hearing Loss, Sensorineural ; Cochlear Implantation ; Cochlear Implants ; Hearing Loss, Central ; Auditory Threshold ; Evoked Potentials, Auditory, Brain Stem

Objective: To explore the value of electrically evoked auditory brainstem response (EABR) monitoring combined with brainstem auditory evoked potential (BAEP) and compound action potential (CAP) monitoring during vestibular schwannoma resection for the protection of the cochlear nerve. Methods: Clinical data from 12 patients with vestibular schwannomas who had useful hearing prior to surgery were analyzed at the PLA General Hospital from January to December 2021. Among them, there were 7 males and 5 females, ranging in age from 25 to 59 years. Before surgery, patients underwent audiology assessments (including pure tone audiometry, speech recognition rate, etc.), facial nerve function evaluation, and cranial MRI. They then underwent vestibular schwannoma resection via the retrosigmoid approach. EABR, BAEP, and CAP were simultaneously monitored during surgery, and patients' hearing preservation was observed and analyzed after surgery. Results: Prior to surgery, the average PTA threshold of the 12 patients ranged from11 to 49 dBHL, with a SDS of 80% to 100%. Six patients had grade A hearing, and six patients had grade B hearing. All 12 patients had House-Brackman grade I facial nerve function prior to surgery. The MRI indicated tumor diameters between 1.1 and 2.4 cm. Complete removal was achieved in 10/12 patients, while near-total removal was achieved in 2/12 patients. There were no serious complications at the one-month follow-up after surgery. At the three-month follow-up, all 12 patients had House-Brackman grade I or II facial nerve function. Under EABR with CAP and BAEP monitoring, successful preservation of the cochlear nerve was achieved in six of ten patients (2 with grade B hearing, 3 with grade C hearing, and 1 with grade D hearing). Successful preservation of the cochlear nerve was not achieved in another four patients (all with grade D hearing). In two patients, EABR monitoring was unsuccessful due to interference signals; however, Grade C or higher hearing was successfully preserved under BAEP and CAP monitoring. Conclusion: The application of EABR monitoring combined with BAEP and CAP monitoring during vestibular schwannoma resection can help improve postoperative preservation of the cochlear nerve and hearing.
Male ; Female ; Humans ; Adult ; Middle Aged ; Neuroma, Acoustic/complications* ; Hearing/physiology* ; Evoked Potentials, Auditory, Brain Stem/physiology* ; Cochlear Nerve ; Hearing Loss, Sensorineural/etiology* ; Retrospective Studies ; Postoperative Complications/prevention & control*