Cochlear nerve (CN) atrophy is a prognostic marker for cochlear implantation outcomes in acquired sensorineural hearing loss (ASNHL). However, conventional MRI confines assessment to the nerve trunk. This 5-T MRI study aimed to assess the feasibility of visualizing the cochlear aperture segment and investigate its potential atrophy. Consecutive ASNHL patients and healthy controls (HCs) who underwent 5-T MRI were prospectively enrolled. Visualization of the cochlear aperture segment was scored. The CN sizes at the cochlear aperture and the internal acoustic meatus segments were measured and compared between groups. Factors associated with cochlear aperture segment size were explored using within-subject correlation analyses. Inter- and intra-observer agreements were assessed. This study included 71 ASNHL patients and 50 matched HCs, wherein 121 affected ears in 66 patients and 98 control ears were measured. The cochlear aperture segment showed a good agreement of visualization and measurement. Affected ears had a lower visualization score of the cochlear aperture segment and smaller absolute CN sizes than controls. After facial nerve normalizing, affected ears had the lower CN size at the cochlear aperture segment but not at the internal acoustic meatus segment. The ratio of the cochlear aperture segment size to the internal acoustic meatus segment size was significantly lower in affected ears than in controls (0.66 ± 0.20 vs. 0.75 ± 0.35; p = 0.045). Interaural differences in hearing loss duration and pure-tone audiometry correlated with interaural differences in the cochlear aperture segment sizes (Rho = −0.247 to −0.356, p < 0.05). The cochlear aperture segment of CN can be reliably visualized and measured at 5-T MRI. CN atrophy is confirmed in ASNHL ears, notably at the cochlear aperture segment. Cochlear aperture segment size was associated with hearing loss duration and severity. Questions The secondary cochlear nerve atrophy was reported in acquired sensorineural hearing loss (SNHL) patients, but the cochlear nerve at the cochlear aperture segment has not been evaluated. Findings The cochlear aperture segment of the cochlear nerve shows atrophy in acquired SNHL patients using 5-T MRI. Its size is associated with duration and hearing loss severity. Clinical relevance 5-T MRI holds promise as the workhorse modality for imaging the cochlear nerve for SNHL patients. Cochlear aperture segment atrophy is noted in acquired SNHL ears. The comprehensive assessment of the cochlear nerve offers pathophysiological insights into the secondary nerve atrophy.

Background:The trans-stenotic pressure gradient (TPG) is a critical pathophysiological factor in symptomatic transverse sinus stenosis (TSS) and serves as a principal hemodynamic indicator for determining the necessity of stent placement. However, the gold standard of TPG measurement requires venous manometry guided by digital subtraction angiography, which is an invasive procedure associated with significant technical complexity, substantial cost, and procedural risks. In recent years, there has been growing interest in noninvasive image-based TPG estimation methodologies. However, a comprehensive multivariate analysis incorporating clinical parameters, laboratory biomarkers, and imaging indicators remains conspicuously absent in recent research. The purpose of this study was to investigate the clinical, laboratory, and imaging parameters that exhibit correlations with the TPG in TSS. Methods:Inpatients diagnosed with idiopathic intracranial hypertension or venous pulsatile tinnitus who underwent computed tomography venography (CTV) between September 2016 and October 2023 were retrospectively reviewed. Those with confirmed TSS and who subsequently underwent venous manometry were included. The comparison of parameters between genders was performed through the use of independent samples t-tests for continuous data and chi-squared tests for categorical data. We analyzed the correlation of the TPG with clinical characteristics (pulsatile tinnitus side, gender, age, and body mass index), laboratory results (blood glucose, blood lipid, routine blood examination, laboratory thyroid function test, coagulation test, and serum sex hormone levels), and CTV signs (the degree, length, and type of TSS; outflow laterality of the transverse sinus; and confluence point of the Labbé vein). Independent variables were determined, and a multivariate linear regression model was applied to assess their influences on TPG. Results:The study cohort comprised 95 participants (11 males and 84 females) with a median age of 38 years (interquartile range, 31-49 years). Body mass index (BMI) (P=0.004), hemoglobin (P=0.018), testosterone (P=0.004), and prolactin (P<0.001) were significantly different between genders, while the other parameters were not. The TPG was significantly correlated with age (R=-0.36; P<0.001), the degree of TSS (R=0.53; P<0.001), length of TSS (R=0.36; P<0.001), intrinsic stenosis (R=-0.21; P=0.038), an upstream location of the Labbé vein (R=-0.28; P=0.006), levels of free tetraiodothyronine (R=0.30; P=0.004), triiodothyronine (R=-0.27; P=0.008), D-dimer (R=-0.22; P=0.035), follicle-stimulating hormone (R=-0.28; P=0.006), luteinizing hormone (R=-0.29; P=0.004), and prolactin (R=0.25; P=0.016). After multicollinearity testing and variable adjustment, the degree of TSS, age, and triiodothyronine level were included in the final regression model, resulting in the following equation: y TPG = 7.42 + 11.04x degree of TSS - 0.12x age - 0.03x triiodothyronine (R=0.67; P<0.001). Conclusions:The degree of TSS, patient age, and triiodothyronine level are independently correlated with TPG in patients with symptomatic TSS.

BACKGROUND AND PURPOSE:Isolated congenital middle ear malformation (CMEM) contributes significantly to congenital hearing loss and growth problems. This study aims to compare 0.1-mm isotropic ultra-high-resolution CT (U-HRCT) and conventional high-resolution CT (HRCT) for assessing isolated CMEM, using surgical exploration as the standard. MATERIALS AND METHODS:This single-center retrospective study included patients with surgically confirmed isolated CMEM who underwent U-HRCT or HRCT from January 2015 to April 2025. Middle ear abnormalities were identified based on operative outcomes and 4 subtypes were classified via the Teunissen standard. Two neuroradiologists blinded to surgical outcomes reviewed CT images for 10 subtle structural abnormalities and specific subtypes. The comparison of U-HRCT and HRCT in terms of interobserver and intraobserver agreement and detection of structural abnormalities and subtypes of CMEM were analyzed. RESULTS:The U-HRCT and HRCT groups included 61 patients (69 ears) and 37 patients (44 ears), respectively. U-HRCT exhibited significantly higher interobserver and intraobserver agreement and stronger concordance with surgical findings for all 10 abnormalities compared with HRCT. It also showed superior diagnostic sensitivity for CMEM (100.0% versus 90.9%; P = .013) and outperformed HRCT in differentiating clinical subtypes (0.774 versus 0.352; P<.001). U-HRCT achieved accuracies exceeding 0.85 in identifying all abnormalities and outperformed HRCT in detecting specific abnormalities including abnormal long process of the incus, lenticular process, abnormal stapes superstructure, stapes footplate fixation, and oval window atresia (P < .05). CONCLUSIONS:Isotropic 0.1-mm U-HRCT significantly outperforms conventional HRCT in diagnosing CMEM, differencing subtypes, and detecting subtle abnormalities, supporting its clinical superiority for precise preoperative evaluation.

Background Mitochondrial dysfunction is considered one of the molecular mechanisms underlying age-related hearing loss (ARHL). While some studies have suggested that surtuin 1 (SIRT1) may improve mitochondrial function, delaying the onset of ARHL; other research has indicated that SIRT1 can exacerbate hair cell damage, leading to further hearing loss. We aimed to investigate the role of SIRT1 in ARHL and its associated molecular mechanisms. Methods Eight-week-old male C57BL/6J mice were randomly divided into three groups: control, D-galactose (D-gal), and D-gal+SIRT1. Auditory brainstem response (ABR) was tested to evaluate hearing function. Immunofluorescence (IF) staining was used to assess the number of ribbon synapses. The enzymatic chemistry was applied for measuring reactive oxygen species (ROS) production, and mitochondrial DNA (mtDNA) damage was assessed with RT-PCR. Additionally, western blot (WB) was used to detect SIRT1 protein levels. Results Compared with the control group, the D-gal group exhibited elevated ABR thresholds and decreased ABR I wave amplitude, as well as prolonged latency. The results also revealed a decrease in the number of ribbon synapses and increased ROS levels in the D-gal group, as well as decreased SIRT1 protein. SIRT1 overexpression mitigated hearing loss in D-gal-induced accelerated aging mice, with increased ABR I wave amplitude and shorter latency. WB analysis revealed that SIRT1 overexpression reduced total protein acetylation levels. Furthermore, SIRT1 overexpression decreased ROS production, mitigated mtDNA damage and significantly increased the number of synapses. Conclusions These findings demonstrate that SIRT1 overexpression suppresses oxidative stress in ARHL, thereby mitigating damage to inner hair cell ribbons and delaying the hearing deterioration in ARHL.

Currently, the accepted mechanism of noise-induced hidden hearing loss (NIHHL) is cochlear synaptopathy which disrupts afferent synapses of the cochlear inner hair cells; however, the molecular basis underlying the cochlear synaptopathy remains unclear. In this study, adult mice were subjected to single or twice moderate noise exposure (the 1st , and 2nd NE, respectively) . The results showed that mice after the 1st NE exhibited a temporary threshold shift (TTS) that recovered within two weeks, while immunofluorescence staining revealed loss of ribbon synapses. After 2nd NE, by contrast, permanent threshold shifts were observed, with more severe loss of ribbon synapses. Furthermore, we found that ERK1/2 was phosphorylated (p-ERK1/2) in the cochlea following both the 1st and 2nd NE, and the peak of p-ERK1/2 emerged earlier after the 2nd NE. Administration of the ERK1/2 inhibitor SCH772984 significantly restored hearing compared with controls. Taken together, our findings demonstrate that noise exposure activates ERK1/2 phosphorylation in the cochlea, leading to hearing loss, and indicate that activation of the ERK1/2 pathway may represent a cellular mechanism underlying NIHHL.

Objective:To evaluate the efficacy of triple semicircular canal occlusion （TSCO） in controlling vertigo, its impact on hearing function, and its safety profile in patients with intractable delayed endolymphatic hydrops （DEH）. Methods:A retrospective analysis was conducted on 16 patients with intractable DEH who underwent TSCO at Beijing Friendship Hospital, Capital Medical University, between June 2020 and June 2025. Vertigo control rate, Dizziness Handicap Inventory （DHI） score, pure-tone average （PTA） threshold, and procedure-related complications were assessed preoperatively and at a minimum follow-up of 6 months postoperatively. Results:The postoperative vertigo control was achieved in all patients, with Class A （complete control） achieved in 81.25% （13/16） of patients and Class B （substantial control） in 18.75% （3/16）. The median postoperative DHI total score decreased significantly from 61.63 to 35.81 postoperatively （P<0.001）. Mean PTA increased from（76.46±12.04）dB preoperatively to（90.51±13.44）dB postoperatively, representing a mean deterioration of 14.05 dB. Preoperatively, 13 patients had an average hearing threshold ≤90 dB, while 3 patients had thresholds >90 dB. Postoperatively, 76.9% （10/13） of patients retained usable hearing （≤90 dB HL）, and no cases exhibited significant hearing loss （>30 dB）. All patients experienced transient dizziness or vertigo following surgery but became ambulatory with or without assistance within 1 to 4 days. No severe complications, such as cerebrospinal fluid leakage, facial paralysis, or infection, were observed. Conclusion:Triple semicircular canal occlusion is an effective and safe function-preserving surgical intervention for intractable DEH. It offers reliable vertigo control and significant improvement in quality of life, with an acceptable risk of hearing deterioration.

Objective:Hearing loss is one of the most common sensory impairments among older adults, significantly impacting their quality of life. The Report on Hearing Health in China （2025） systematically reviews the current status, challenges, and strategies regarding hearing health in elderly population in China. This article distills the report's core viewpoints and practical implications. The prevalence of hearing loss among individuals aged 60 and above reaches 11.04%, affecting over 20 million people, and is closely associated with cognitive decline, social isolation, and various chronic diseases. The etiology of age-related hearing loss is complex, involving genetic factors, chronic conditions such as diabetes and hypertension, and environmental influences. While intervention and rehabilitation systems are gradually being established, they remain inadequate because of low hearing aid adoption rates, limited use of cochlear implants, and lagging auditory rehabilitation services. Although relevant policies and standards have been introduced and insurance coverage is expanding, there is still a need to strengthen system construction, professional training, and technological research and development. The report calls for establishing a full-chain service model covering "screening, diagnosis, intervention, and rehabilitation" to promote societal-wide engagement in improving hearing health for the elderly.

The limited regenerative capacity of vestibular hair cells (HCs) in mammals is one of the causes of permanent balance disorders. The transcription factor Atoh1 has been identified as a potential candidate for inducing HC regeneration. However, regulation of Atoh1 alone has proven insufficient to achieve functional recovery of the mammalian vestibule. Elucidating the mechanisms underlying Atoh1-induced regeneration may therefore inform strategies to enhance its therapeutic efficacy. Endogenous Sox2 is required for Atoh1-associated HC formation during embryonic development, yet its role in Atoh1 overexpression-induced HC formation after birth remains unclear. In this study, we conditionally knocked down Sox2 while overexpressing Atoh1 in the utricle of neonatal mice or in diphtheria-toxin-injured adult mice. Atoh1 overexpression stimulated supporting cell proliferation and new HC formation in neonates; however, concomitant Sox2 knockdown attenuated the effects. In the diphtheria-toxin-injured adult utricle, Sox2 downregulation similarly weakened Atoh1-induced HC regeneration. These findings demonstrate that endogenous Sox2 expression is essential for Atoh1-induced HC addition and regeneration in the mouse utricle.

BACKGROUND AND PURPOSE:Inner ear is characterized by fine and intricate anatomy. Due to magnetic inhomogeneity, inner ear imaging has not benefited much from ultra-high field-strength MRI. 5-T may provide an alternative for inner ear imaging. This study aimed to compare image quality and visibility of specific structures between 5-T and 3-T MRI. MATERIALS AND METHODS:Consecutive healthy volunteers who underwent heavily T2-weighted imaging at 3-T and 5-T within one week were prospectively enrolled between September and October 2025. Image quality was rated using Likert scale for overall image, specific inner ear and nerve apparatus. Signal-to-noise ratio, contrast-to-noise ratio and image sharpness were quantitated. Wilcoxon signed-rank tests or paired t tests were used for inter-field comparison. Inter-observer and inter-field agreements were assessed. RESULTS:A total of 22 participants (median age: 40.50[30.00-49.00] years; 10 females; 44 ears) were included. There was no significant difference of overall image quality between 5-T and 3-T across three readers (average median scores: both 4.67; P> 0.999). Compared with 3-T, 5-T demonstrated a superior visibility for posterior ampullary nerve, superior vestibular nerve, cochlear nerve and cochlear aperture segment of cochlear nerve, as well as foramen singular and osseous spiral lamina. The visibility score of inferior vestibular nerve was marginally higher at 5-T than that at 3-T for readers (P=0.054-0.094). No differences of visualizing evaluated membranous labyrinth structures between two field strengths were observed. Signal-to-noise ratio, contrast-to-noise ratio and image sharpness were higher at 5-T than at 3-T. CONCLUSIONS:Compared with 3-T, three-dimensional heavily T2-weighted sequence at 5-T improved the detectability of nerves significantly, particularly segments coursing through bony ducts, as well as the foramen singular and osseous spiral lamina.

BACKGROUND:Endolymphatic hydrops (EH) detected by MRI following intratympanic injection of gadolinium is identified in the contralateral ears to the affected side of some patients with clinically unilateral Ménière's disease (MD). OBJECTIVE:To investigate the prevalence and clinical relevance of endolymphatic hydrops in the contralateral ear of patients with unilateral Meniere's disease. MATERIAL AND METHODS:We analyzed 66 patients with definite unilateral MD. Participants underwent audiological examinations and clinical assessments, including the Tinnitus Handicap Inventory (THI), Dizziness Handicap Inventory (DHI), disease duration, and vertigo characteristics. Besides, bilateral intratympanic gadolinium-enhanced 3D-Real IR magnetic resonance imaging (MRI) was performed. RESULTS:EH was detected in 24.2% of contralateral ears, predominantly presenting as isolated vestibular or cochlear hydrops. Cochlear hydrops in the contralateral ear showed a positive correlation with hearing loss severity (χ²= 3.95, p < 0.05) and disease duration (t = 3.5, p < 0.001). Conversely, vestibular hydrops in the contralateral ear exhibited no significant associations with hearing loss or disease duration (p > 0.05). Furthermore, no correlations were found between contralateral EH and THI, DHI, or vertigo duration. CONCLUSION AND SIGNIFICANCE:Our study confirms that contralateral EH is a prevalent imaging finding in unilateral MD, highlighting the disease's potential for subclinical bilateral involvement.

Following severe injury, most cells in the vestibular sensory epithelium undergo cell death, whereas the surviving epithelial cells initiate a repair program that leads to the formation of a flat epithelium (FE). However, the mechanisms underlying FE formation remain unclear. In this study, we combine in vivo and in vitro approaches to investigate the role of TGF-β signaling in this process. Our findings reveal dynamic changes in the expression of epithelial-mesenchymal transition (EMT) markers during FE formation, and a rapid activation of the TGF-β signaling pathway following injury. In vitro experiments show that exogenous application of TGF-β1 accelerates wound closure, whereas inhibition of TGF-β signaling with SB431542 delays wound healing. Mechanistically, we demonstrate that suppression of TGF-β signaling reduces the number of α-SMA-positive cells and downregulates the expression of mesenchymal markers. Conversely, activation of TGF-β signaling enhances the expression of EMT-associated transcription factors and mesenchymal markers. These results suggest that TGF-β signaling plays a critical role in regulating FE formation following severe damage to the utricular sensory epithelium, likely through the modulation of EMT.

Abstract SIRT3 protects against metabolic stress-induced cellular damage by regulating mitochondrial homeostasis and autophagy-related pathways in various tissues. It has also been implicated in protecting cochlear hair cells and synapses after noise exposure. However, whether protection associated with SIRT3 modulation in noise-induced hearing loss (NIHL) is accompanied by autophagy-related changes remains unclear. Here, we found that AAV-SIRT3 delivery was associated with reduced LC3B level and increased p62 accumulation in the noise-exposed cochlea, suggesting attenuation of noise-associated autophagy-related marker changes. AAV-SIRT3 delivery was also associated with reduced 4-HNE accumulation, partial preservation of mitochondrial membrane potential, and a decreased Ac-SOD2/SOD2 ratio. These findings suggest that AAV-SIRT3-associated protection against NIHL is accompanied by reduced mitochondrial oxidative injury and attenuation of autophagy-related cochlear stress responses.

The gene therapy achieved by AAV-mediated otoferlin-overexpression is an effective therapeutic strategy for congenital deafness. However, achieving its physiological and endogenous patterns of expression remains challenging. Here, we generate the homologous mutation Otof c.1315 C > T (p.R439*), equivalent to OTOF c.1273 C > T (p.R425*) found in humans with profound deafness, to create a nonsense mutation-induced deaf mouse model. We then deliver the ‘RESTART v3’ system, which is a CRISPR-free RNA base editor for nonsense mutation suppression, into the cochlea of the mice. We achieve physiological otoferlin expression, and the edited premature termination codon is reverse-mutated to the original amino acid. We observe significant hearing restoration and enhancement of the behavioral auditory startle reflex. Thus, our study presents a successful RNA editing strategy to significantly restore hereditary deafness in mice carrying the specific Otof nonsense mutation, which holds great promise for future clinical translation.

PURPOSE:To assess the relationship between the ultra-high-resolution computed tomography (U-HRCT) score of oval window region (OWR) involvement and audiometry in otosclerosis. METHODS:This study enrolled patients with clinically suspected otosclerosis who underwent U-HRCT examination. The analysis included 71 ears from 50 patients (mean age, 38.0 [34.0-49.8] years). The ears were divided into the conductive hearing loss group (group A, 20 ears) and mixed hearing loss group (group B, 51 ears). The CT scores of bone involvement around the oval window (0, none; 1, <25 %; 2, 25 %-50 %; 3, 50 %-75 %; 4, >75 %) and stapes footplate involvement (0, none; 1, <50 %; 2, >50 %) were evaluated and summed to obtain the CT score of OWR involvement. The Mann-Whitney U test was used to compare the difference in the distribution of the CT score of OWR involvement between groups A and B. Spearman's rank correlation analysis was performed to evaluate the association between the CT score of OWR involvement and the mean air conduction (AC), bone conduction (BC) and air-bone gap (ABG). RESULTS:The CT score of OWR involvement in group B was significantly higher than that in group A (p = .014). The correlation coefficients between the CT score of OWR involvement and the mean AC, BC, and ABG threshold were 0.74 (p < .001), 0.52 (p < .001), and 0.48 (p < .001). CONCLUSION:U-HRCT possesses the ability to clearly depict the OWR in otosclerosis. The U-HRCT-derived OWR involvement score of otosclerosis could reflect the type and degree of hearing loss.

OBJECTIVES:To explore the interaction between the M1 macrophages and Schwann cells (SCs) in auditory nerve myelin. METHODS:We conducted co-culture experiments using SCs from the auditory nerve myelin and induced M1 macrophages from 6-week-old C57BL/6 mice. The co-cultured group was set up as an experimental group, while the control groups were assigned as separated cultures of SCs and macrophages alone. The cultured cells were evaluated by cell number and morphology; further, the functions of the cells were detected by the secretion of Brain-Derived Neurotrophic Factor (BDNF) and phagocytic ability. RESULTS:SCs from the auditory nerve were purified and cultured, showing exponential growth. The BDNF secretion value of SCs was 0.444 ± 0.031 ng/ml. M1 polarization of mouse bone marrow macrophages was successfully induced, and the absorbance value of the macrophages phagocytosis was 0.144 ± 0.003. The co-cultured model presented significant shortening of the spindle-shaped bipolar protrusions of SCs, and the SCs number in co-cultured group was reduced by about 50 % compared with the SCs in control group. the secretion of BDNF value in the co-cultured group was reduced to 0.02 ± 0.007 ng/ml (P < 0.001). In addition, the absorbance value of M1 macrophages phagocytosis in the co-cultured group was significantly reduced to 0.104 ± 0.001 (P < 0.001). CONCLUSION:Both M1 macrophages and SCs in auditory nerve myelin were significantly damaged in the co-cultured group.

OBJECTIVES:To investigate the association between the vestibular aqueduct (VA) and endolymphatic hydrops (EH) in patients with Meniere's disease (MD) using three-dimensional real inversion recovery (3D-real IR) sequences. METHODS:This retrospective study included patients diagnosed with unilateral MD who underwent computed tomography (CT) and 3D-real IR sequencing. The VA course was identified on CT, and its visibility was assessed using a 3D-real IR sequence. The presence and severity of the cochlear and vestibular EH were evaluated. VA visualization was classified as Grade 0, whereas nonvisualization was classified as Grade 1. Differences in VA visibility between the affected and unaffected ears were compared, and correlations between VA visibility and EH severity were analyzed. Finally, the diagnostic efficacy of various MD indicators was assessed. RESULTS:A total of 56 patients with unilateral MD were analyzed. The incidence rates of cochlear or vestibular EH were higher in the affected ear group than in the unaffected ear group (p < 0.001). The rates of nonvisualization of the VA in the affected and unaffected ears were 91.1% and 41.1%, respectively, with a statistically significant difference (χ 2 = 31.226, p < 0.001). The VA visualization status was positively correlated with vestibular and cochlear EH (p < 0.001). The area under the curve for diagnosing MD using combined VA nonvisualization and EH was 0.876, which was significantly higher than that obtained using EH alone (Z = 3.414, p = 0.001). CONCLUSION:VA visibility on 3D-real IR sequences may assist in the diagnosis of MD and associated EH. LEVEL OF EVIDENCE: 3:

Background:Single-cell RNA-sequencing (scRNA-seq) has emerged as a powerful tool for cancer research, enabling in-depth characterization of tumor heterogeneity at the single-cell level. Recently, several scRNA-seq copy number variation (scCNV) inference methods have been developed, expanding the application of scRNA-seq to study genetic heterogeneity in cancer using transcriptomic data. However, the fidelity of these methods has not been investigated systematically. Methods:We benchmarked five commonly used scCNV inference methods: HoneyBADGER, CopyKAT, CaSpER, inferCNV, and sciCNV. We evaluated their performance across four different scRNA-seq platforms using data from our previous multicenter study. We evaluated scCNV performance further using scRNA-seq datasets derived from mixed samples consisting of five human lung adenocarcinoma cell lines and also sequenced tissues from a small cell lung cancer patient and used the data to validate our findings with a clinical scRNA-seq dataset. Results:We found that the sensitivity and specificity of the five scCNV inference methods varied, depending on the selection of reference data, sequencing depth, and read length. CopyKAT and CaSpER outperformed other methods overall, while inferCNV, sciCNV, and CopyKAT performed better than other methods in subclone identification. We found that batch effects significantly affected the performance of subclone identification in mixed datasets in most methods we tested. Conclusion:Our benchmarking study revealed the strengths and weaknesses of each of these scCNV inference methods and provided guidance for selecting the optimal CNV inference method using scRNA-seq data.

ABSTRACT Background Hearing loss (HL) significantly impacts quality of life and economic status worldwide. Chronic inflammation is suggested to influence hearing, yet the connection with inflammation‐related indexes in the general population is not well understood. Methods This cross‐sectional study analyzed data from 7231 adults from six cycles (2005–2012 and 2015–2018) of the National Health and Nutrition Examination Survey (NHANES). It examined the correlation between systemic immune‐inflammatory biomarkers (NLR, SII, PLR, and LMR) and auditory threshold shifts/HL using multivariable logistic regression models. Smooth curve fitting visualized the association, and log‐likelihood ratio tests determined the existence of thresholds in biomarker effects, supplemented by subgroup analyses. Results After adjustments, significant associations were found for low‐frequency HL with ln‐transformed NLR (OR = 1.29, 95% CI: 1.06–1.56, p = 0.0116), ln‐SII (OR = 1.31, 95% CI: 1.08–1.59, p = 0.0065), and ln‐LMR (OR = 0.74, 95% CI: 0.60–0.91, p = 0.00043). For high‐frequency HL, similar patterns were observed for ln‐SII (OR = 1.25, 95% CI: 1.05–1.48, p = 0.0105) and ln‐LMR (OR = 0.76, 95% CI: 0.64–0.90, p = 0.007); however, the association with ln‐NLR did not reach statistical significance (OR = 1.18, 95% CI: 1.00–1.40, p = 0.0562). NLR and SII positively correlated with HL, while LMR showed a negative correlation. No significant association was noted with PLR. Dose–response relationships were observed, particularly between LMR and all categorized frequencies of HL and between SII and high‐frequency HL. Subgroup analyses indicated that NLR and SII are risk factors for HL in healthy BMI males, with LMR being more protective in males, the elderly, and diabetics. Conclusions Systemic inflammation‐related indexes, especially SII, are predictive of both high‐ and low‐frequency HL, highlighting the role of inflammatory homeostasis in hearing health. LMR may offer protective effects, particularly in specific subgroups. These findings suggest potential targets for HL treatment by regulating inflammation, warranting further investigation into their clinical application.

Objective:To summarize the clinical characteristics and surgical outcomes of endolymphatic sac tumor(ELST),and improve the experience of diagnosis and treatment of this disease.Methods:A retrospective a-nalysis was conducted on the clinical data of patients with ELST who underwent surgical treatment by the Depart-ment of Otolaryngology Head and Neck Surgery,Beijing Friendship Hospital,Capital Medical University from January 2015 to December 2024.The clinical and image features,perioperative management,surgical methods and follow-up results of the disease were summarized.Results:Of the 6 cases,4 were male and 2 were female.The primary clinical characteristics were hearing loss(6 cases),tinnitus(5 cases),dizziness(2 cases),facial paralys-is(1 case),and headache(1 case).CT and MRI of temporal bone were performed in all cases.The manifestation of CT was a space occupying lesion centered on the region of endolymphatic sac,accompanied by bone destruction and intertumoral calcification.MRI showed tumor center isosignal and peripheral hypersignal in T1 and T2 se-quences in 3 cases,and mixed hypersignal in T1 and T2 sequences in 3 cases.Enhancement was observed in all ca-ses on the enhanced scan.5 cases underwent DSA examination and showed the tumors were supplied by the occipi-tal artery(2 cases),posterior auricular artery(4 cases),and the bunch of internal carotid artery(1 case).Emboli-zation of the feeding artery was performed in 3 patients.Five patients underwent tumor resection.Translabyrin-thine approach were performed in 4 cases,and middle cranial fossa approach was performed in 1 case.All cases followed up for 24 to 70 months with no distant metastases or death.Two patients experienced twice recurrences and were treated with surgical operation.The tumors were found to be closely related to the internal auditory canal or dura during the surgery.Conclusion:The clinical manifestations of ELST are not typical,and hearing loss is the most common clinical symptom.CT and MRI exhibit typical imaging characteristics.ELST has a risk of re-currence,and the tumor should be carefully managed when invade to the internal auditory canal and dura to reduce postoperative recurrence.

Congenital hearing loss is a major type of sensorineural deafness. Recently, Dmxl2 has been identified as a new gene associated with familial deafness. However, its role in auditory development remains unclear. This study investigated the expression and localization of DmX-like protein 2 (DMXL2), encoded by Dmxl2, in the mouse cochlea at various postnatal stages. DMXL2 was predominantly expressed in inner and outer hair cells, with the highest levels at postnatal day 7, followed by a rapid decline, nearly disappearing by day 14. To elucidate Dmxl2's function, we administered short hairpin RNA (shRNA) targeting Dmxl2 to the cochlea within 24 h post-birth, effectively knocking down its expression in the mouse inner ear. This resulted in profound hearing loss in treated mice, accompanied by disruption of development of cochlear ribbon synapses and spiral ganglion cells (SGCs). In conclusion, our study demonstrates the critical role of Dmxl2 in hearing development, suggesting it as a potential molecular target for future gene therapy in hearing loss treatment.