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

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

Objective: To analyze the surgical efficacy of patients with mixed hearing loss and otosclerosis with different air bone gap (ABG) before surgery, and to provide reference for the prognosis evaluation of otosclerosis surgery. Methods: The clinical data of 108 cases(116 ears) of otosclerosis who had undergone stapes fenestration technique artificial stapes implantation in Xiangya Hospital of Central South University from November 2013 to May 2020 and had mixed hearing loss before surgery were collected, including 71 women(76 ears)and 37 men (40 ears), with an average age of 38.5 years. According to preoperative pure tone audiometry ABG, they were divided into three groups: group S, 15 dB≤ABG<31 dB, a total of 39 ears; group M, 31 dB≤ABG<46 dB, a total of 58 ears; and group L, ABG≥46 dB, 19 ears in total. The hearing outcomes of three groups of patients at 6-12 months after surgery were compared and analyzed using SPSS 24.0 statistical software. Results: A total of 3 patients (group S: 2 cases; group L: 1 case) experienced severe sensorineural hearing loss after surgery and were not included in the statistical analysis. After surgery, the pure tone hearing threshold of patients with otosclerosis in each group was significantly improved compared to before surgery, with an average air conduction threshold improvement of(21.6±13.4) dB. The difference between before and after surgery was statistically significant(t=17.13, P<0.01). The average bone conduction threshold improved by(3.7±7.6) dB, and the difference was statistically significant before and after surgery(t=5.20, P<0.01). The postoperative ABG was(18.3±9.3) dB, which was significantly reduced compared to preoperative(36.2±8.6)dB. Among the three groups of patients, the L group had the highest improvement in air conduction threshold[(29.9±10.8)dB], while the S group had the lowest improvement[(15.7±11.4)dB]. There was no statistically significant difference in post operative pure tone hearing thresholds between the three groups(P>0.05). The postoperative ABG in group S was the smallest[(16.5±9.0)dB], while in group L, the postoperative ABG was the largest[(20.5±10.0)dB]. Compared with group S, group M and group L still had a large residual ABG at 2 000 Hz after surgery. The bone conduction threshold of both S and M groups improved to some extent after surgery compared to before (P<0.01). Conclusions: Surgery can benefit patients with mixed hearing loss and otosclerosis with different preoperative ABG. Patients with small preoperative ABG have better surgical results and ideal ABG closure at all frequencies after surgery. Patients with large preoperative ABG can significantly increase the gas conduction threshold during surgery, but certain frequencies of ABG may still be left behind after surgery. The improvement effect of surgery on bone conduction threshold is not significant. Patients should be informed of treatment methods such as hearing aids based on their actual situation for selection.
Male ; Humans ; Female ; Adult ; Bone Conduction ; Otosclerosis/surgery* ; Hearing Loss, Mixed Conductive-Sensorineural/surgery* ; Stapes Surgery/methods* ; Treatment Outcome ; Auditory Threshold ; Hearing ; Audiometry, Pure-Tone ; Deafness ; Retrospective Studies

The qualitative, quantitative, and localization analysis of hearing loss is one of the important contents of forensic clinical research and identification. Pure-tone audiometry is the "gold standard" for hearing loss assessment, but it is affected by the subjective cooperation of the assessed person. Due to the complexity of the auditory pathway and the diversity of hearing loss, the assessment of hearing loss requires the combination of various subjective and objective audiometric techniques, along with comprehensive evaluation based on the case situation, clinical symptoms, and other examinations to ensure the scientificity, accuracy and reliability of forensic hearing impairment assessment. Objective audiometry includes acoustic impedance, otoacoustic emission, and various auditory evoked potentials. The frequency-specific auditory brainstem response (ABR), 40 Hz auditory event related potential, and auditory steady-state response are commonly used for objective hearing threshold assessment. The combined application of acoustic impedance, otoacoustic emission and ABR can be used to locate hearing loss and determine whether it is located in the middle ear, cochlea, or posterior cochlea. This article reviews the application value of objective audiometry techniques in hearing threshold assessment and hearing loss localization, aiming to provide reference for forensic identification of hearing loss.
Humans ; Reproducibility of Results ; Auditory Threshold/physiology* ; Evoked Potentials, Auditory, Brain Stem/physiology* ; Hearing Loss/diagnosis* ; Audiometry, Pure-Tone/methods* ; Clinical Medicine

High level noise can damage cochlear hair cells, auditory nerve and synaptic connections between cochlear hair cells and auditory nerve, resulting in noise-induced hearing loss (NIHL). Recent studies have shown that animal cochleae have circadian rhythm, which makes them different in sensitivity to noise throughout the day. Cochlear circadian rhythm has a certain relationship with brain-derived neurotrophic factor and glucocorticoids, which affects the degree of hearing loss after exposure to noise. In this review, we summarize the research progress of the regulation of cochlear sensitivity to noise by circadian rhythm and prospect the future research direction.
Animals ; Auditory Threshold ; Circadian Rhythm ; Cochlea ; Evoked Potentials, Auditory, Brain Stem/physiology* ; Hair Cells, Auditory ; Hearing Loss, Noise-Induced ; Noise/adverse effects*

Objective: To study the protective effects of metformin on noise-induced hearing loss (NIHL) and its differential protein omics expression profile. Methods: In January 2021, 39 male Wistar rats were randomly divided into control group, noise exposure group and metformin+noise exposure group, with 13 rats in each group. Rats in the noise exposure group and metformin+noise exposure group were continuously exposed to octave noise with sound pressure level of 120 dB (A) and center frequency of 8 kHz for 4 h. Rats in the metformin+noise exposure group were treated with 200 mg/kg/d metformin 3 d before noise exposure for a total of 7 d. Auditory brainstem response (ABR) was used to test the changes of hearing thresholds before noise exposure and 1, 4, 7 d after noise exposure in the right ear of rats in each group. Tandem mass tag (TMT) quantitative proteomics was used to identify and analyze the differentially expressed protein in the inner ear of rats in each group, and it was verified by immunofluorescence staining with frozen sections. Results: The click-ABR thresholds of right ear in the noise exposure group and metformin+noise exposure group were significantly higher than those in the control group 1, 4, 7 d after noise exposure (P<0.05) . The click-ABR threshold of right ear in the metformin+noise exposure group were significantly lower than that in the noise exposure group (P<0.05) . Compared with the noise exposure group, 1035 up-regulated proteins and 1145 down-regulated proteins were differentially expressed in the metformin+noise exposure group. GO enrichment analysis showed that the significantly differentially expressed proteins were mainly involved in binding, molecular function regulation, signal transduction, and other functions. Enrichment analysis of KEGG pathway revealed that the pathways for significant enrichment of differentially expressed proteins included phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway, focal adhesion, diabetic cardiomyopathy, mitogen, and mitogen-activated protein kinase (MAPK) signaling pathway. Immunofluorescence experiments showed that compared with the noise exposure group, the fluorescence intensity of insulin-like growth factor 1 receptor (IGF1R) in the metformin+noise exposure group was increased, and the fluorescence intensity of eukaryotic translation initiation factor 4E binding protein 1 (eIF4EBP1) was decreased. Conclusion: Noise exposure can lead to an increase in rat hearing threshold, and metformin can improve noise-induced hearing threshold abnormalities through multiple pathways and biological processes.
Animals ; Auditory Threshold/physiology* ; Cochlea ; Ear, Inner ; Evoked Potentials, Auditory, Brain Stem/physiology* ; Hearing Loss, Noise-Induced/prevention & control* ; Male ; Metformin/pharmacology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Rats ; Rats, Wistar

Non-steady state noise has become the main type of workplace noise. Compared with steady state noise, non-steady state noise may cause more serious hearing loss. This paper reviews the new situation of occupational hearing loss caused by non-steady state noise exposure, the overview of international noise exposure assessment standards and new challenges, and the new evidence of non-steady state noise induced hearing loss, so as to provide the basis for the future research of non-steady state noise induced hearing loss.
Auditory Threshold ; Hearing Loss, Noise-Induced ; Humans ; Noise ; Noise, Occupational/adverse effects* ; Occupational Diseases/epidemiology*

Audiology ; Auditory Threshold ; Humans

Objective: To investigate the effect of autoinflation on the prognosis of OME in children. Methods: Total of 325 pediatric patients, age ranged from 3 to 8 years, with OME(486 ears)diagnosed in our department from January 2019 to January 2020 were collected. Among them, 177 were males, 148 were females. Disease course ranged from 25 to 86 days. According to watchful waiting and autoinflation application during follow-up, these children were divided into two groups including 183 cases(271 ears) and 142 cases(215 ears), respectively. The average auditory threshold and tympanogram curve type in two groups were analyzed in the period of 3 months follow-up, and the recovery of OME was evaluated. Results: At the end of 1- and 2- month follow-up, the auditory threshold of patients in autoinflation group was significantly lower than that in watchful waiting group (t=2.139 5 and 2.680 6, P<0.05). However, at the end of 3- month follow-up, there was no significant difference between two groups (t=1.158 5, P>0.05). At the end of 1-, 2- and 3- month follow-up, 89 (33%, 89/271), 200 (74%, 200/271), 220 (81%, 220/271) and 176 (82%, 176/215), 178 (83%, 178/215), 183 (85%, 183/215) ears in watchful waiting group and autoinflation group had a hearing threshold <20 dB HL, respectively, in which ears with auditory threshold<20 dB HL in watchful waiting group were significantly less than those in autoinflation group at the end of 1 and 2 month follow-up (P<0.05), However, ears with auditory threshold<20 dB HL in watchful waiting group were not significantly different from that in the autoflation group at the end of 3- month follow-up (P>0.05). The proportion of ears with type A tympanogram curve was 74%(159/215), 79%(170/215), and 85%(183/215) at the end of 1-, 2- and 3- month follow-up in autoinflation group and 36%(98/271), 71%(192/271) and 76%(206/271) in watchful waiting group, respectively. Proportion of ears with type A tympanogram curve in autoflation group was significantly higher than that in watchful waiting group (P<0.05). Conclusion: Autoinflation can improve the hearing of children with OME in early stage, restore normal middle ear pressure, increase recovery rate, and reduce the choice of surgical treatment of OME.
Auditory Threshold ; Child ; Child, Preschool ; Female ; Hearing ; Humans ; Male ; Middle Ear Ventilation ; Otitis Media with Effusion/diagnosis* ; Prognosis

OBJECTIVES: To explore the relationship between the frequency characteristics and response threshold of auditory steady-state response (ASSR), auditory brainstem response (ABR) and 40 Hz auditory event related potential (40 Hz AERP), and their application values in forensic medicine. METHODS: Thirty volunteers with normal hearing (60 ears) were selected to perform pure tone audiometry (PTA) threshold and ASSR, ABR and 40 Hz AERP response threshold tests in the standard sound insulation shielding room, and the results were statistically analyzed by SPSS 22.0 software. RESULTS: At 0.5 kHz and 1.0 kHz frequencies, the correlation between 40 Hz AERP response threshold and PTA threshold was good, which was better than that of ASSR and ABR response threshold. At 2.0 kHz and 4.0 kHz frequencies, the correlation between ASSR and ABR response thresholds and PTA threshold was good, which was better than that of 40 Hz AERP response threshold. CONCLUSIONS To evaluate the hearing at 0.5 kHz and 1.0 kHz frequencies, it is recommended to use 40 Hz AERP and ASSR to comprehensively assess the PTA threshold of the subjects. To evaluate the hearing at 2.0 kHz and 4.0 kHz frequencies, ABR and ASSR are recommended to assess the PTA threshold of subjects comprehensively. The combination of ASSR, ABR and 40 Hz AERP can improve the accuracy of hearing function evaluation.
Acoustic Stimulation/methods* ; Audiometry, Evoked Response ; Audiometry, Pure-Tone ; Auditory Threshold/physiology* ; Evoked Potentials, Auditory, Brain Stem/physiology* ; Forensic Medicine ; Hearing/physiology* ; Humans