BACKGROUND:Sequential bilateral sudden sensorineural hearing loss (Se-BSSHL) may occur after an initial unilateral episode, but the risk factors for contralateral ear involvement remain unclear. This research aims to identify risk factors associated with the occurrence of contralateral ear in patients suffering from sudden sensorineural hearing loss (SSHL). By leveraging machine learning algorithms, the study uses patients' demographic and clinical data to develop a predictive model. METHODS:We conducted an analysis on clinical data from 939 patients admitted to the Ear Department of the Chinese PLA General Hospital from 2008 to 2022, categorizing them into unilateral sudden sensorineural hearing loss (USSHL) and sequential bilateral sudden sensorineural hearing loss (Se-BSSHL) groups. Stratified sampling was executed to maintain a proportional representation of unilateral versus bilateral cases, leading to the creation of seven internal and three external datasets. Variable selection was performed using a decision tree-based recursive feature elimination method. We applied five-fold cross-validation on the internal datasets and conducted model testing on the external datasets. Four machine learning algorithms-random forest, extreme gradient boosting, logistic regression, and support vector machine-were used to build the predictive model and conduct external validation. Model efficacy was primarily appraised using the area under the receiver operating characteristic curve (AUC-ROC), calibration curves, decision curve analysis (DCA), and additional performance metrics including accuracy, precision, recall, and F1-score on the test set. The influence of the variables was illustrated through Shapley value plots. Statistical methods such as the t-test, analysis of variance, and chi-squared test were used. RESULTS:We observed a 12.57% (118/939) incidence rate of contralateral ear complications in USSHL patients with otherwise normal hearing. The predictive model incorporated 19 variables, among them, age, hearing loss degree, and sex are the three most significant features influencing the occurrence in the healthy ear of the USSHL group. An increase in age and a more severe degree of hearing loss are risk factors for the occurrence of the disease, and females have a higher risk of disease occurrence. Other high-risk test indicators for disease occurrence can be summarized and categorized into two types of risk factors: lipoprotein dysfunction (total cholesterol, high-density lipoprotein cholesterol, apolipoprotein A1) and inflammation (eosinophils, lymphocyte count, neutrophil count). The AUC of the model on the external test reached 0.77, with an accuracy of 88%, a precision of 84%, a recall of 88%, and an F1 value of 0.85 using the default classification threshold of 0.5, demonstrating robust predictive capabilities. CONCLUSION:This investigation elucidates the risk factors for contralateral ear disease in USSHL patients and establishes a robust predictive model for such occurrence, which offers substantial reference value for managing and preventing complications in USSHL patients.

OBJECTIVE:To identify prognostic factors for unilateral idiopathic sudden sensorineural hearing loss (SSNHL) in pediatric and adult patients, and to compare therapeutic efficacy between these age groups: METHODS: This retrospective cohort study included 1947 hospitalized patients (219 pediatric, 1728 adult) with unilateral idiopathic SSNHL from January 2008 to December 2022. All patients received inpatient therapy following the Chinese Guidelines for SSNHL, with pediatric dosing adjusted for age and weight. To compare therapeutic outcomes, multivariable logistic regression, full propensity score matching (PSM), restricted cubic spline (RCS), and machine learning algorithms were employed. RESULTS:Baseline median ages were 13 (IQR, 10-15) years for pediatric and 43 (IQR, 33-50) years for adult patients. Shared independent prognostic factors in both groups included audiogram configuration, degree of hearing loss, and treatment-onset time. Furthermore, after matching, pediatric and adult patients had comparable complete recovery (18.7% vs. 16.4%) and overall efficacy rates (52.5% vs. 54.1%). The therapeutic window was identified as 14 days for children and 15 days for adults. Consistent with this, treatment-onset time emerged as the most influential feature in predictive models, with pediatric outcomes achieving an area under the curve (AUC) of 0.849 and adult outcomes an AUC of 0.901. CONCLUSIONS:Pediatric and adult patients with unilateral idiopathic SSNHL share major prognostic factors. Therapeutic efficacy is comparable between groups when appropriate treatment is provided. Early intervention, ideally within 2 weeks of symptom onset, is critical to maximize auditory recovery. LEVEL OF EVIDENCE: 3:

Noise-induced hearing loss (NIHL) is the second most prevalent occupational disease in China. Due to its insidious onset, patients are often diagnosed at an irreversible stage, yet high-quality prospective cohorts addressing this critical issue remain limited. We established a multicenter prospective cohort-the Study of Health Effects from Noise Generated in China (SHENG)-with the primary objectives of systematically characterizing the epidemiological features, identifying environmental and genetic risk factors, elucidating molecular mechanisms, and investigating systemic health effects of NIHL, ultimately providing a scientific foundation for evidence-based prevention and control strategies. The baseline survey of SHENG was completed in 2023, covering eight enterprises across seven provinces and enrolling 4,660 young male workers (mean age 23.5 years). Based on high-frequency pure-tone average (3-8 kHz), 27.4% of participants were classified as having hearing loss, though most of them did not report subjective hearing difficulties. Compared with the normal hearing group, the hearing loss group had significantly more noise exposure events, higher exposure rates to occupational co-hazards such as dust and vibration, and poorer hearing protection practices. SHENG is planned to conduct follow-up assessments every 1-2 years. Through longitudinal follow-up and multidimensional data integration, this cohort will establish an "environmental-clinical-genetic" risk assessment model, elucidate the dynamic progression of NIHL and its associations with systemic diseases, and provide key evidence for refining occupational noise exposure standards and developing precision prevention strategies tailored to susceptible populations.

Objective:To analyze the magnetic resonance hydrography results of the inner ear in patients with total deafness-type sudden sensorineural hearing loss , and to explore the incidence and correlation with therapeutic efficacy in patients with internal auditory canal vascular loops. Methods:Audiological and imaging data were collected from 517 patients with sudden sensorineural hearing loss who were hospitalized in our hospital. All patients underwent T2WI rapid imaging sequence MRI examination, and the vascular loops of the patients were graded according to the Chavda grading method. The impact of different grades of vascular loops on the clinical characteristics and prognosis of the patients was analyzed. Statistical methods such as chi-square test and non parametric rank sum test to analyze the impact of internal auditory canal vascular loops on the clinical characteristics and hearing prognosis of patients with sudden total deafness. Results:From May 2009 to June 2024, a total of 517 hospitalized patients with sudden deafness were analyzed. It was found that: ①110 patients had abnormal hydrography in the internal auditory canal, including 32 patients with mastoiditis, 30 patients with sinus, ethmoid sinus, and maxillary sinus abnormalities, 15 patients with semicircular canal abnormalities, 7 patients with high jugular bulb, and 18 patients with fine or poorly displayed internal auditory canal nerves; ②276 patients with sudden sensorineural hearing loss accompanied by vascular loops, including 156 ears on the affected side and 158 ears on the healthy side with Chavda classification of grade Ⅰ; 104 ears on the affected side and 83 ears on the healthy side with type Ⅱvascular loops; There were 16 ears on the affected side of type Ⅲ and 14 ears on the healthy side. There was no significant difference in the distribution of vascular loops between the patient and the affected side（P>0.05）; ③The frequency of vascular loops in female patients is higher than that in males（P<0.05）, but no significant differences were found in the degree of hearing loss and hearing outcomes at different frequencies among patients with different grades of vascular loops（P>0.05）. ④The incidence of tinnitus in patients with vascular loop grades Ⅰ-Ⅲ was 92.9%, 83.7%, and 100.0%, respectively. There was a statistically significant difference in the incidence of tinnitus among patients with different grades of vascular loops（P<0.05）. Conclusion:For patients with sudden total deafness, more attention should be paid to their inner ear magnetic resonance imaging results. The vascular loop of the internal auditory canal is a possible cause of tinnitus in some patients with sudden total deafness.

Objective:Age-related hearing loss（ARHL） is one of the most common sensory degenerative disorders in the elderly, characterized by high prevalence, insidious onset, and progressive deterioration. Recent studies indicate that ARHL not only impairs communication and quality of life in older adults, but is also significantly associated with the development of cognitive impairment and Alzheimer's disease. However, its underlying pathogenesis remains incompletely understood, and the relationship between clinical phenotypes of ARHL and cognitive decline has yet to be clearly defined. ARHL occupies a pivotal position in geriatric health management and in the prevention of neurodegenerative diseases, yet it has not been systematically conceptualized or mechanistically examined. In this review, we summarize the current research progress on ARHL and cognitive impairment, analyze possible mechanisms linking the two conditions, evaluate the potential cognitive protective effects of hearing interventions, and propose priority directions for future research and clinical practice. With advances in multidisciplinary collaboration and technological innovation, the prevention and treatment of ARHL are expected to enter a new era of greater precision and efficiency, offering novel opportunities to reduce the risk of cognitive impairment and improve overall health in older populations.

Objective:To further classify refractory low-frequency sudden sensorineural hearing loss（SSNHL） and investigate the clinical characteristics and prognostic differences among various subtypes. Methods:A retrospective analysis was conducted on 208 patients with refractory low-frequency SSNHL who were hospitalized in Department of Audiology and Vestibular Medicine, Senior Department of Otolaryngology Head and Neck Surgery, Sixth Medical Center of the PLA General Hospital after failing conventional outpatient treatment. Based on clinical manifestations, patients were classified into four subtypes: migraine-associated type, hypotension or low intracranial pressure type, endolymphatic hydrops type, and other types. The clinical characteristics and prognostic outcomes were compared among the groups. Results:Significant differences were observed among the four groups in terms of sex distribution, affected ear side, accompanying symptoms（tinnitus, aural fullness, vertigo, or dizziness）, and progression to Meniere's disease（all P<0.05）. Pairwise comparisons revealed that the proportion of females in the migraine-associated group was significantly higher than that in the endolymphatic hydrops and other groups（all P<0.05）. The left ear was more frequently affected in the endolymphatic hydrops group than in the hypotension or low intracranial pressure group（P=0.027）. Tinnitus was significantly more common in the endolymphatic hydrops and other groups than in the hypotension or low intracranial pressure group（all P<0.05）. The migraine-associated group exhibited significantly higher rates of aural fullness, vertigo or dizziness, and progression to Meniere's disease compared to the other group （all P<0.05）. Regarding prognosis, the cure rates in the migraine-associated and hypotension or low intracranial pressure groups were 61.9% and 57.8%, respectively, significantly higher than those in the endolymphatic hydrops（11.8%） and other groups（27.0%）（all P<0.05）. The recurrence rate in the migraine-associated group was 52.4%, significantly higher than that in the other group（21.4%）（P<0.05）. The migraine-associated group demonstrated a significantly higher incidence of high-frequency hearing loss compared to the other groups（all P<0.05）. Long-term follow-up revealed that this subtype was associated with more frequent hearing fluctuations, while hydrops and circulatory types retained potential for hearing recovery. Conclusion:Significant differences in clinical characteristics and prognosis exist among subtypes of refractory low-frequency SSNHL.The migraine-associated subtype is prone to fluctuating or recurrent hearing loss and has a higher risk of high-frequency hearing impairment. The hypotension or low intracranial pressure subtype has a relatively favorable prognosis, with a lower incidence of cochlear symptoms such as tinnitus and aural fullness. The endolymphatic hydrops subtype is associated with a poorer prognosis, although hearing may improve during long-term follow-up.

Temperature-sensitive auditory neuropathy (TSAN) is a rare disease and a distinctive subtype of auditory neuropathy, characterized by fluctuating hearing thresholds and speech recognition influenced by body or environmental temperature. It is most associated with biallelic variants in the OTOF gene. Despite growing genetic insights, its long-term natural history remains poorly characterized, and the functional consequences of specific OTOF variants are incompletely understood. This retrospective case series included 5 Han Chinese patients with TSAN carrying OTOF variants. Comprehensive audiological evaluations, including auditory brainstem response (ABR), otoacoustic emissions (OAE), cochlear microphonics (CM), pure-tone audiometry, and speech recognition assessment, were performed. Genetic analyses included whole-exome sequencing, Sanger validation, in silico pathogenicity prediction, and structural modeling. Long-term clinical follow-up ranged from 5 to 21 years. All patients initially presented with mild-to-moderate fluctuating hearing loss, absent ABR, and preserved OAE and/or CM, consistent with AN. Genetic analysis identified 7 rare OTOF variants, including 2 frameshift variants (p. Gln994Valfs*7 and p. Leu795Serfs*5), 1 nonsense variant (p. Arg1134Ter), and 4 missense variants (p. Arg1607Trp, p. Gly541Ser, p. Trp536Cys, and p. Ala1667Asp). Most variants affected evolutionarily conserved residues and were predicted to be deleterious, while structural modeling suggested that the missense variants may alter local protein conformation and stability. Long-term follow-up revealed marked inter-individual variability in auditory outcomes. Several patients achieved near-normal auditory performance without intervention, with Categories of Auditory Performance scores of 7 and Speech Intelligibility Rating scores of 5, whereas others showed persistent speech perception deficits despite only moderate hearing thresholds. Cochlear implantation improved auditory performance in selected patients. OTOF-related TSAN demonstrated substantial clinical heterogeneity but generally favorable long-term functional outcomes in this cohort. These findings contribute to the characterization of the OTOF mutational landscape in TSAN, highlight the importance of long-term monitoring in this rare disease, and support individualized management strategies guided by both genotype and functional auditory performance.

Objective:To examine the association between pure-tone thresholds at different frequencies and cognitive performance among adults aged 60-69 years using data from the NHANES. Methods:This cross-sectional study included NHANES participants aged 60-69 years who completed standardized pure-tone audiometry and the digit symbol substitution test（DSST）. Low-frequency, speech-frequency, and high-frequency PTAs were calculated. Weighted multivariable linear regression models were applied with progressive adjustment for sociodemographic factors, education, smoking status, obesity, and cardiovascular disease risk. Subgroup and interaction analyses were also performed. Results:A total of 1 232 participants were included, of whom 486（39.4%） comprised the hearing loss group. The median DSST score in the hearing loss group was significantly lower than that in the normal hearing group（54 vs 62, P<0.001）. In the unadjusted model, elevated pure-tone average（PTA） thresholds across all tested frequencies were significantly associated with lower DSST scores（P<0.001）. After multivariate adjustment, elevated PTA thresholds at low frequencies, speech frequencies, and high frequencies remained independently associated with lower DSST scores, with the strongest association observed for speech-frequency PTA. Subgroup analysis revealed a significant interaction between race and the association of PTA with DSST score（P for interaction=0.047）. Conclusion:Among adults aged 60-69 years, elevated pure-tone thresholds across frequency bands are independently associated with poorer cognitive performance, particularly at speech frequencies. Sociodemographic factors and cardiovascular disease risk factors may partially explain the observed associations.

Objective To explore the comorbidity patterns between hearing loss and symptomatic dizziness (HL-SD) in middle-aged and older adults.Methods This cross-sectional study used data from the 1999 to 2004 National Health and Nutrition Examination Survey (NHANES). After excluding incomplete data, 2961 participants aged 40-69 were analyzed. Logistic regression models, restricted cubic splines (RCS), and subgroup analyses assessed the association between hearing thresholds and dizziness. Univariate and multivariate logistic models and LASSO regression identified risk factors related to HL-SD. Propensity score matching (PSM) evaluated the correlation between hearing loss and dizziness treatment efficacy.Results Among participants, 28.67% had hearing loss, and 22.99% reported dizziness, with 8.00% experiencing both. Increased hearing thresholds were significantly associated with a higher risk of dizziness, with each 1 dB increase in speech-frequency PTA increasing dizziness risk by 1.6%. Various factors, including gender, income, arthritis, and diabetes, were linked to the comorbidity of HL-SD. However, hearing loss did not significantly affect dizziness treatment outcomes.Conclusions Hearing loss is significantly associated with an increased risk of symptomatic dizziness in middle-aged and older adults, influenced by various factors. However, it does not appear to affect dizziness treatment efficacy.

ABSTRACT Objective To compare the association of vertigo with rates of frequency‐specific hearing recovery in pediatric and adult patients with unilateral idiopathic sudden sensorineural hearing loss (SSNHL). Methods A total of 80 pediatric and 444 adult patients hospitalized with SSNHL were included in this study. Clinical and audiological data were collected, and frequency‐specific hearing recovery percentages before and after treatment were compared between pediatric and adult SSNHL patients with and without vertigo. Results In pediatric SSNHL patients with vertigo, the median recovery rates at 250–500 Hz, 1000–2000 Hz, and 4000–8000 Hz were 62.5%, 28.2%, and 21.1%, respectively, whereas those without vertigo showed higher median recovery rates of 90.3%, 82.1%, and 56.5%. Similarly, adult SSNHL patients with vertigo exhibited median recovery rates of 53.2%, 33.7%, and 24.6% across the same frequency ranges, compared to 88.9%, 76.6%, and 53.3% in adults without vertigo. In both pediatric and adult cohorts, hearing recovery decreased progressively with increasing frequency. Patients with vertigo exhibited consistently lower recovery across all frequency bands compared to those without vertigo. However, no statistically significant differences in frequency‐specific recovery were observed between pediatric and adult SSNHL cohorts. Conclusion The incidence of vertigo increases with the severity of hearing loss in SSNHL ranging from moderately severe to total deafness. Vertigo is a prognostic factor associated with poorer hearing recovery across all frequencies, underscoring its importance as a critical clinical indicator in the management of SSNHL. Level of Evidence 3

Objective:To characterize speech recognition in presbyacusis and its associated neurophysiological and cortical structural features, and to explore structure-function-behavior relationships within the presbyacusis phenotype. Methods:Thirty elderly patients with presbyacusis(HI) and thirty-three healthy young controls(NH) completed a behavioral task involving Putonghua monosyllabic word recognition. Additionally, mismatch negativity (MMN) responses using the oddball paradigm to assess neurophysiological sensitivity, and acquired 3D T1-weighted MRI combined with Freesurfer to quantify cortical thickness (CTh) in six auditory-related regions of interest (ROIs) were recorded. Between-group differences were assessed, and exploratory associations were examined within the HI group; key associations were further evaluated using hierarchical regression adjusting for sex, age, and pure-tone average (PTA). Results:The HI group exhibited significantly poorer speech recognition performance, with prolonged MMN latency and increased amplitude compared to the NH group. CTh was generally thinner (except for the right supratemporal gyrus), with a left-hemisphere bias in the planum polare (PP). Within the HI group, exploratory unadjusted correlations suggested associations of speech recognition rate maximum (SRRmax) with MMN amplitude and right heschl's gyrus (HG) CTh; however, after adjustment for sex, age, and PTA, MMN amplitude and right HG CTh were not significant predictors, and adding these predictors did not improve model fit, whereas PTA remained independently associated with SRRmax. However, no significant associations were found between MMN features and the anatomical characteristics of the ROIs. Conclusions:Presbyacusis is associated with altered speech recognition, neurophysiological responses, and auditory-related cortical structure compared with young controls. Within the HI group, peripheral hearing thresholds accounted for a major proportion of variance in speech recognition, while MMN/MRI associations observed in exploratory analyses were attenuated after covariate adjustment, warranting replication in larger and better age-matched cohorts.

POU4F3 (DFNA15) is an established causative gene for autosomal dominant non-syndromic hearing loss (ADNSHL); however, its mutational spectrum in the Chinese population remains incompletely characterized. This study aimed to expand the mutational spectrum of POU4F3 in the Chinese population, to characterize the clinical phenotypes of affected individuals, to describe the proportion of POU4F3-related families in this referral cohort, and to summarize the global reporting distribution of pathogenic POU4F3 variants in ADNSHL. Among 83 unrelated ADNSHL families evaluated at two tertiary referral centers, nine families harboring POU4F3 variants were identified through whole-exome sequencing and validated by Sanger sequencing with co-segregation analysis. Comprehensive audiological assessments, including pure-tone audiometry, extended high-frequency audiometry, and tinnitus evaluation, were performed on all available family members. Variants were classified according to ACMG/AMP guidelines. Genotype–phenotype correlations were analyzed by integrating data from our cohort with 43 previously published variants. Nine distinct POU4F3 variants were identified, including four novel variants (c.149_152dup, c.687_688delCA, c.704 C > T, and c.709_710delTC) and five previously reported variants (c.371 C > A, c.592 C > A, c.706 C > T, c.952G > A, and EX1-EX2E Del). POU4F3 variants accounted for 10.8

BACKGROUND:The cochlear microphonic (CM) primarily reflects the composite receptor potential of outer hair cells (OHCs), providing an objective assessment of OHC mechanoelectrical transduction (MET) capacity. However, systematic studies on CM in basic research remain scarce, and baseline CM values for CBA/CaJ mice have not yet been established. Moreover, whether CM can functionally differentiate between auditory neuropathy (AN) and noise-induced hearing loss (NIHL) has not been systematically addressed. This study aimed to establish normative CM reference values for CBA/CaJ mice and to explore the utility of CM as an objective electrophysiological tool for assessing OHC function across different pathophysiological conditions. NEW METHOD:CM was recorded from the round window in three mouse models: wild-type (WT) CBA/CaJ mice (1, 2, and 7 months), Aifm1 p.R450Q knock-in AN mice, and NIHL models of permanent threshold shift (PTS) and temporary threshold shift (TTS). Input-output (I/O) nonlinearity and frequency-specific were analyzed. RESULTS:In WT mice, CM amplitude exhibited an approximately linear relationship with stimulus intensity at levels ≤ 90 dB SPL. When the intensity exceeded 90 dB SPL, the amplitude saturated and subsequently declined, demonstrating nonlinear characteristics under high-intensity stimulation. Compared to 1- and 2-month-old WT mice, CM amplitude was reduced at 7 months of age. In AN mouse models, CM waveforms remained generally normal, but amplitude increased at 1 month and declined by 7 months. In noise-exposed mice, CM amplitude significantly decreased in the PTS group, while only a slight reduction was observed in the TTS group. CONCLUSION:This study establishes normative CM values for CBA/CaJ mice and demonstrates that CM profiling provides a functional differentiation between AN and two types of NIHL. These findings support CM as a robust, objective tool for assessing OHC function in murine models and encourage broader implementation of CM testing in both preclinical research and clinical diagnostics.

OBJECTIVES:To explore the correlations between genotype and phenotype, disease progression, and outcomes of interventions in patients with auditory neuropathy (AN) caused by OTOF gene variants. DESIGN:Patients with AN associated with OTOF variants were identified using whole-exome or panel sequencing. Variants were interpreted according to the American College of Medical Genetics and Genomics guidelines. Audiometric tests were conducted, including auditory brainstem response, distortion product otoacoustic emission (DPOAE), behavioral audiometry/pure-tone audiometry, etc. The genetic and audiological characteristics of the patients were analyzed. The disease progression and intervention of the patients were followed up, and phenotype differences were analyzed in combination with genotype. RESULTS:A total of 43 AN patients were identified with OTOF gene variants, including seven novel variants. The pure-tone average was 89.20 ± 17.81 dB HL, with 91.11% having severe hearing loss or greater. The auditory steady-state response and DPOAE results deteriorated with increasing disease duration. Twenty-five patients underwent cochlear implantation, with the Category of Auditory Performance score of 7.00 (5.00, 7.50). Patients with biallelic loss-of-function variants showed a trend toward worse hearing but a higher DPOAE response rate. Similarly, patients with a single allele variant causing protein truncation also had a higher DPOAE extraction rate. CONCLUSIONS:Seven novel mutations of the OTOF gene were identified, which enriched the spectrum of OTOF gene variants. Most of the AN patients with OTOF variants showed severe to profound hearing loss, with the progression of the disease course. The cochlear implantation effects were good, which were related to the intervention age and duration. There is a correlation trend between OTOF variants' genotype and phenotype.

OBJECTIVES:The study aimed to characterize the features of vestibular schwannoma (VS) patients with sudden hearing loss (SHL) to provide guidance for clinicians. METHODS:We conducted a retrospective study, which included 626 participants with VS. Clinical and audiometric characteristics, imaging features, and postoperative hearing preservation rate were compared and analyzed between the SHL group and non-SHL group. RESULTS:The SHL group consisted of 139 patients (22%), which included 65 males and 74 females (47%/53%). The peak age ranges for the onset of hearing loss were 35-39 years (17%) in the SHL group and 45-49 years (16%) in the non-SHL group. The average ages of medical consultation in the SHL and non-SHL groups were 42 ± 13 years and 45 ± 12 years (P = 0.011). The most common interval from hearing loss onset to consultation was 1 month (29%) in the SHL group, whereas it was 7-12 (18%) months in the non-SHL group. As the Koos grade increased, the proportion of participants with serviceable hearing in the SHL group gradually declined. The residual hearing preservation rate in the SHL group was significantly higher than that in the non-SHL group (84% vs. 63%, P = 0.024). CONCLUSIONS:VS patients with SHL are associated with a younger onset age at, lower Koos grade, high-frequency hearing loss and higher postoperative residual hearing preservation rate, indicating SHL could be one of the important factors for predicting postoperative residual hearing preservation.

王秋菊: 随着人口老龄化进程的加快,老年性听力损失与认知障碍的共病现象逐渐引起临床与科研领域的高度重视.大量研究提示,听力下降不仅影响老年人沟通能力与生活质量,还可能与认知功能减退呈显著相关,甚至在一定程度上加速痴呆的发生与发展.

Purpose It is essential to investigate the audiological profiles of Williams syndrome in a multicultural context. This study aims to examine the characteristics and management of hearing loss in Chinese children with Williams syndrome and provide references for future clinical management. Method Between January 2007 and March 2022, families with at least 1 WS patient was recruited from the Newborn Cohort Study of Hearing Loss. Audiological tests were performed, and then appropriate medical management was offered. Furthermore, an overview of the hearing loss phenotype in Williams syndrome in different locations was reviewed. Results A total of two families with at least 1 Williams syndrome patient were recruited from the Newborn Cohort Study of Hearing Loss (ChiCTR2100049765). We identified moderately severe sensorineural or conductive hearing loss that emerged as early as the infancy period in Williams syndrome subjects in Chinese children. Our results extended the reported onset ages of hearing loss in WS from late childhood or early adulthood to the infancy period. We also found that with early diagnosis, proper management, and regular monitoring, children with Williams syndrome could return to a normal or near-normal school life. Conclusions Our study demonstrated the distinct hearing profile in Chinese children with Williams syndrome for the first time. This cohort of WS subjects extends the reported onset ages of hearing loss in WS from late childhood or early adulthood to the infancy period, indicating the importance of clinicians screening and monitoring the hearing status of individuals with WS as early as possible. These data provide references for otolaryngologists and paediatricians to inform the clinical understanding and management of hearing loss in Williams syndrome.

Objectives: The aim of this study was to investigate the causal relationships between sleep-associated traits and hearing difficulties in noise (HDinN) by Mendelian randomization (MR) analysis. Design: Single nucleotide polymorphisms associated with chronotype, insomnia, sleep duration, daytime dozing or sleeping, and ease of getting up in the morning were extracted from European population genome-wide association study pooled data for bidirectional MR analysis. The MR-Egger regression, the inverse variance weighted technique, and the weighted median method were used for data analysis. The study was then expanded to include South Asian, East Asian, African, and Greater Middle Eastern populations. Results: MR analysis indicated that in European populations, ease of getting up in the morning is a protective factor for HDinN (odds ratio [OR] = 0.932, p = 4.22 × 10−5, p FDR = 5.62 × 10−4), while shorter sleep duration was a risk factor (undersleepers: OR = 1.164, p = 0.002, p FDR = 0.014). In addition, there was an indicative causal association between daytime dozing and HDinN (OR = 1.089, p = 0.046, p FDR = 0.123). The conclusions were consistent in African populations (ease of getting up: OR = 0.696, p = 0.012, p FDR = 0.041, sleep duration: OR = 0.677, p = 0.032 p FDR = 0.091, daytime dozing: OR = 1.164, p = 0.002, p FDR = 0.014). In the reverse direction, there was a significant causal association between HDinN and both chronotype (OR = 1.413, p = 0.011, p FDR = 0.042) and ease of getting up in the morning (OR = 0.668, p = 1.75 × 10−5, p FDR = 3.49 × 10−4) in European populations, with similar conclusions respectively reached in East Asian (OR = 1.085, p = 0.010, p FDR = 0.045) and African populations (OR = 0.936, p = 0.002, p FDR = 0.012). Furthermore, although not observed in European populations, exploratory studies in non-European populations suggested a potential association between insomnia and HDinN (East Asian: OR = 1.920, p = 0.011, p FDR = 0.043, African: OR = 2.080, p = 0.004, p FDR = 0.019, South Asian: OR = 1.981, p = 1.59 × 10−4, P FDR = 0.002, Greater Middle Eastern: OR = 2.394, p = 0.002, p FDR = 0.012), and vice versa (Greater Middle Eastern: OR = 1.056, p = 0.014, p FDR = 0.044). Conclusions: This study identified a potential bidirectional causal relationship between sleep-associated traits and HDinN. However, the underlying mechanisms of the causal relationships reported here have yet to be elucidated.

De novo mutations (DNMs) are significant genetic factors contributing to sporadic hearing loss (HL) and complex HL syndromes. To analyze the genetic counseling characteristics and interpretation of pathogenic DNMs for sporadic HL, we retrospectively analyze the clinical information of probands and their parents from 410 sporadic HL core pedigrees enrolled in the "Chinese Deafness Genome Project (CDGP)" between October 2015 and October 2023. We apply family trio-based genome sequencing (targeted gene capture and high throughput sequencing, mitochondrial genome sequencing, and copy number variants analysis) and validate the samples of their unaffected-parents. Homologous allele sequencing is used to identity by descent (IBD) in the DNM family trios. The results reveal that 7.3% (30 cases) of the probands in these sporadic hearing loss core pedigrees carry 17 types of autosomal dominant gene de novo single nucleotide variants (SNVs), insertions/deletions (Indels), and one type of de novo copy number variation, encompassing all types of DNM. Among them, WFS1 c.2051C>T, ATP1A3 c.2452G>A, and ACTG1 c.94C>T are common DNM in sporadic HL. The genotype C>T transversion exhibit a high number (34.6%). Clinical feature analyses also show that 56.7% (17/30) of the probands have non-syndromic HL, but more than half of them (52.9%, 9/17) carry pathogenic genotypes clearly associated with "syndromic HL", possibly exhibiting temporary "mimic" non-syndromic HL phenotypic characteristics. The average parental ages at childbirth for the 30 probands are 29.4 years for fathers and 28.3 years for mothers, with 13.3% of fathers or mothers aged ≥35 years. Additionally, among the family structure of the proband of genetic counseling, 63.3% are single-child families with a clear desire for another child, and 16.7% of the probands' parents seek prenatal genetic counseling for conceiving a "second child". During genetic counseling, it is essential to test the "family proband-parents' trios" core pedigree as a unit to analyze the genetic contribution of DNMs to HL. Furthermore, there is a certain correlation between the occurrence of DNMs and increasing parental age at childbirth. Therefore, for families with a history of DNM-associated sporadic HL, it is necessary to collect clinical information such as the parental age at childbirth and obstetric history of hearing-healthy parents. For these families planning another child, it is recommended to undergo prenatal diagnosis for the identified DNM pathogenic variations after conception and pay attention to the pregnancy outcome.