Dongzhen Yu

Background: Cisplatin is an effective chemotherapeutic agent, but its clinical use is limited by dose-dependent ototoxicity that leads to irreversible sensorineural hearing loss. Accumulating evidence implicates impaired autophagy–lysosomal homeostasis in cisplatin-induced ototoxicity. Transcription factor EB (TFEB), a master regulator of autophagy and lysosomal biogenesis, represents a promising therapeutic target. Clotrimazole, an FDA-approved antifungal drug with emerging cytoprotective properties, has not been investigated for its potential to mitigate cisplatin-induced ototoxicity. Methods: We evaluated the protective effects of clotrimazole using House Ear Institute-Organ of Corti 1 cells, cochlear explants, and an adult C57BL/6J mouse model of transtympanic cisplatin ototoxicity. Apoptosis, reactive oxygen species (ROS), and autophagy flux were assessed using biochemical assays and imaging. RNA-sequencing was performed to identify transcriptional pathways regulated by clotrimazole. TFEB dependence was verified using small interfering RNA knockdown and pharmacological inhibition of AMP-activated protein kinase (AMPK). Cochlear function was assessed using auditory brainstem responses (ABRs), and hair-cell and synapse survival were quantified by immunofluorescence. Results: Clotrimazole significantly reduced cisplatin-induced apoptosis, ROS generation, and calcium overload. Transcriptomic profiling and functional assays revealed robust activation of autophagy. Clotrimazole promoted AMPK activation, suppressed mTORC1 signaling, and enhanced TFEB nuclear translocation. TFEB or AMPK inhibition abrogated these protective effects. In vivo , intratympanic clotrimazole preserved hair cell survival, maintained ribbon synapses, and significantly reduced ABR threshold shifts. Conclusions: Clotrimazole protects against cisplatin-induced ototoxicity by activating the AMPK–mTOR–TFEB axis and restoring autophagy lysosomal homeostasis. These findings support TFEB-targeted autophagy activation as a promising therapeutic strategy for preventing cisplatin-induced hearing loss. Antioxid. Redox Signal. 44, 928–950.

Background: Current unidimensional cancer evaluation systems limit precise cancer control. This study establishes a novel burden–quality framework that integrates disease burden and quality-of-care index (QCI) to better assess cancer management effectiveness globally. Methods: The QCI was derived by principal component analysis of six standardized indicators using the Global Burden of Disease data (1990–2021). A four-quadrant framework integrated QCI with disease burden to classify 34 cancers across 204 countries/regions. The sociodemographic index (SDI) and gender disparity ratios (GDR) were used to assess inequalities. Results: Substantial heterogeneity exists in the burden and QCI across 34 cancers. Highly fatal cancers such as TBL cancers (tracheal, bronchus, and lung cancers) and pancreatic cancers are persistently trapped in a “high burden-low quality” dilemma. In contrast, high-burden breast cancer and low-burden thyroid cancer demonstrate superior QCI, though the latter may carry overtreatment risks. Socioeconomic factors have a profound influence on intervention equity, with SDI exhibiting a strong positive correlation with QCI ( r = 0.90, P < 0.001) but a significant negative correlation with GDR ( r = −0.71, P < 0.001). Notably, the trend of QCI improvement and overall reduction in cancer burden is asynchronous: high-survival cancers and high-SDI regions showed slow QCI gains, middle-SDI regions exhibited substantial increases, while low-SDI areas remained persistently disadvantaged. Demographic disparities further exacerbated these inequities – older populations bore a disproportionate disease burden yet achieved the fastest QCI improvements, whereas adolescent groups maintained high baseline quality but stagnated in progress. Additionally, gender disparities were pervasive, with females receiving better-quality care for most cancers and across most regions. Conclusion: This multidimensional burden–quality framework shifts cancer evaluation from singular evaluation to precision intervention. It emphasizes: (1) optimizing resources for high-burden–low-quality cancers, (2) avoiding overtreatment in low-burden cancers, and (3) reducing inequities linked to socioeconomic disparities and vulnerable groups (especially elderly and male patients). This research provides a foundation for precise and equitable global cancer control.

Objectives. Temporal bone squamous cell carcinoma (TBSCC) is the most common subtype of temporal bone malignancy. However, its low incidence, high misdiagnosis rate, and the difficulty of conducting large-scale studies and clinical trials have limited researchers’ understanding of its occurrence and progression, and diagnostic and therapeutic biomarkers remain lacking. Addressing these gaps requires a clearer understanding of TBSCC tumor heterogeneity and microenvironment. This study aimed to characterize the tumor heterogeneity and microenvironment of TBSCC.Methods. Single-cell RNA sequencing (scRNA-seq) is an effective approach for interrogating tumor heterogeneity. Here, we report scRNA-seq data for TBSCC. We collected and sequenced 113,344 cells from nine samples (five cancer tissues and four histologically verified adjacent normal temporal bone tissues) obtained from six patients with TBSCC.Results. The proportion of S-phase cancer cells was higher in samples with tumor invasion, and the pseudotime trajectory of cancer cells closely corresponded with the TBSCC differentiation level. We also detected higher communication intensity between certain immune cell pairs in cancer tissues than in histologically verified adjacent normal temporal bone tissues. In addition, we identified several cancer-related genes as potential diagnostic markers of TBSCC.Conclusion. This study is the first to characterize the complex heterogeneity and tumor microenvironment of TBSCC using scRNA-seq, providing new avenues for diagnosing, classifying, and treating this rare carcinoma.

Background: Cochlear implant (CI) users require long-term auditory-speech rehabilitation to achieve optimal outcomes, yet access to continuous and structured rehabilitation remains limited. Mobile health technologies offer a potential approach to improve the accessibility and continuity of rehabilitation services. Objective: This study aims to develop a WeChat-based auditory-speech rehabilitation system for Mandarin-speaking CI users and to conduct a preliminary validation of its usability and measurement consistency. Methods: Guided by a goal-oriented digital design framework, a WeChat-based system was developed to assess six domains of auditory and speech rehabilitation. A total of 20 Mandarin-speaking CI users were recruited from Shanghai Sixth People’s Hospital. Usability and app quality were assessed using the System Usability Scale (SUS) and User Version of the Mobile App Rating Scale (uMARS), respectively. Measurement consistency was evaluated using the intraclass correlation coefficient (ICC), weighted Cohen’s kappa (κ), and Bland-Altman analyses. Results: 20 Mandarin-speaking CI users completed the study. Usability assessment demonstrated favorable ratings (SUS = 71.50, SD = 13.58; uMARS = 4.19, SD = 0.50). The system-generated Categories of Auditory Performance classification showed excellent agreement with the rater (weighted κ = 0.97, 95% CI: 0.93-1.00). Articulation intelligibility scores demonstrated high consistency with rater assessments (system vs. rater 1: ICC = 0.97; system vs. rater 2: ICC = 0.94), with minimal bias observed in Bland-Altman analysis. Conclusion: This WeChat Mini Program provides preliminary support for the feasibility of a digital auditory-speech rehabilitation approach for Mandarin-speaking CI users. Further studies are needed to validate its broader applicability and effectiveness in out-of-hospital rehabilitation.

Background This study develops a Quality of Care Index (QCI) to evaluate global disparities in care quality for five head and neck cancer (HNC) subtypes—thyroid, larynx, lip and oral cavity, nasopharynx, and other pharynx cancers—from 1990 to 2021, addressing the issue of existing indicators not fully reflecting cancer quality. Methods We developed a QCI for five HNC subtypes using data from the Global Burden of Disease Study 1990–2021. The QCI was constructed through principal component analysis of six epidemiological indicators. Trends in age-standardized DALY rates (ASDR) and QCI were assessed globally, regionally, nationally and by Socio-demographic Index (SDI). Results From 1990 to 2021, ASDR declined markedly for larynx and nasopharynx cancers, whereas thyroid, lip and oral cancer, and other pharynx cancers decreased only in high-SDI regions, remaining stable or rising in low- and middle-SDI regions. QCI improved for all subtypes. High-SDI regions consistently exhibited a ‘high-quality, low-burden’ pattern, with the highest absolute QCI values but limited relative gains; low-SDI regions, in contrast, faced “high burden and low quality” and, despite lower absolute QCI, showed the largest improvements over time. Subtype-specific patterns were evident: nasopharynx cancer achieved the greatest QCI gains, larynx cancer showed consistent ASDR decline and QCI improvement across all SDI levels, and thyroid cancer improved in QCI despite ASDR increases in low- to middle- SDI regions. Lip and oral cancer, and other pharynx cancers exhibited persistent high burden in lower SDI regions, with modest QCI gains. Conclusions Global HNC care quality has improved, but reductions in disease burden and gains in QCI were not fully aligned. Substantial inequalities persist across cancer subtypes and SDI regions. Strengthening care infrastructure and optimizing HNC management in resource-limited settings are needed to reduce disparities.

Vestibular schwannoma (VS) is a benign tumor that can result in significant neurological and otological complications. The mechanisms underlying its development and spatial heterogeneity remain poorly understood. In this study, we analyzed single-cell RNA sequencing (scRNA-seq) data from three previously published vestibular schwannomas (VS1-3), along with spatial transcriptomics data from two additional specimens (VS_S1-2). Our results identified a VEGFA-enriched Schwann cell (SC) subtype in scRNA-seq data, which was validated by spatial transcriptomics. This subtype also exhibited a significant positive correlation with NOV ^hi SCs expression. These cells were centrally localized within tumor tissue. Furthermore, spatial analysis provided new insights into SC-stromal cell interactions, and we constructed a preliminary cellular atlas of VS tissues, enhancing our understanding of tumor growth dynamics.

Background Hearing loss in children has become a pressing public health issue, with otitis media (OM) being a leading cause. This study aims to comprehensively assess the prevalence and burden of OM-induced hearing loss in children. Methods Data from the Global Burden of Disease (GBD) database were used. We evaluated the Age-standardized Prevalence Rates (ASPR), Age-standardized Years Lived with Disability rates (ASYR), and Estimated Annual Percentage Changes (EAPC) over the past 32 years. The analysis included stratification, correlation analysis, and projections. Results From 1990 to 2021, the global prevalence of OM-induced hearing loss in children under 15 years increased from 31.18 million cases to 34.71 million cases, representing an 11.32% increase. The ASPR slightly decreased from 1793.38 to 1725.39 per 100,000 children, with an EAPC of -0.13. Boys had a higher prevalence and burden compared to girls, and the highest ASPR and ASYR were observed in children aged 5–9 years. Regions with higher Socio-Demographic Index (SDI) showed significant reductions in both prevalence and burden, while low-middle SDI regions bore a heavier burden, with ASPR 1.81 times higher and cases number 6.08 times higher than high SDI regions. Additionally, East Asia showed the largest decrease, while South Asia had the highest ASPR. Conclusion Although the global burden of OM-induced hearing loss has improved, South Asia and low-middle SDI regions continue to face a significant burden, with insufficient healthcare resources likely being a major issue. Additionally, continuing to advance pneumococcal vaccination and other preventive measures is equally crucial for alleviating this burden.