Beijing Tongren Hospital

SLC26A4 is a major causative gene for hereditary hearing loss, its mutation spectrum shows pronounced population specificity. In Chinese populations, patients predominantly carry biallelic mutations, and compound heterozygous genotypes are prevalent, which results in a wide spectrum of auditory phenotypes. However, how different alleles interact within these contexts to shape phenotypic variability remains poorly understood. We employed cellular and mouse models to explore the allele-specific mechanisms associated with two novel mutations, a frameshift mutation and a missense mutation, in compound heterozygous that share the same splice-site pathogenic allele. In vitro, wild-type (WT) and mutant (c.574delC, c.1211C>A) SLC26A4 constructs were expressed in HeLa cells to assess pendrin localization. Both mutations reduced membrane enrichment and increased intracellular retention. In vivo, compound heterozygous knock-in mouse models (Slc26a4c.574delC/c.919-2A>G and Slc26a4c.1211C>A/c.919-2A>G) were generated using CRISPR/Cas9. The auditory function and cochlear pathology were investigated. Both compound mutants exhibited elevated ABR thresholds, with more severe hearing loss in Slc26a4c.574delC/c.919-2A>G mice. Correspondingly, these mice showed marked hair cell disruption, stereociliary loss, and cochlear structural abnormalities, whereas the Slc26a4c.1211C>A/c.919-2A>G mice displayed milder changes. Transcriptomic profiling examined by bulk RNA-sequencing revealed broader differential expression in Slc26a4c.574delC/c.919-2A>G mice, enriched in structural and developmental pathways, while the missense model showed predominantly immune-related signatures. Our findings demonstrate that allele-specific functional divergence in compound heterozygous SLC26A4 mutations leads to distinct auditory dysfunction, cochlear pathology, and transcriptional programs. These findings provide mechanistic insight into the phenotypic heterogeneity of hearing loss and may indicate future allele-specific interventions or therapeutic strategies.

Mutation in USH2A gene cause autosomal recessive retinitis pigmentosa (RP) and Usher syndrome type II (USH2), constituting over 50% of USH2 and approximately 7% of RP. Here, we report the establishment of a human induced pluripotent stem cell (iPSC) line, BTHBIOi002-A, derived from the peripheral blood mononuclear cells (PBMCs) of a USH2 patient with compound heterozygous mutation in USH2A (c.[2512C>T]; [2802T>G]), using the non-integrating episomal plasmids delivered by electroporation with OCT4, SOX2, NANOG, LIN28, c-Myc, and KLF4. The established iPSC line was validated for the karyotype stability, pluripotency markers, and the ability to differentiate into all three germ layers.

Background: Chronic rhinitis, including allergic rhinitis (AR) and nonallergic rhinitis (NAR), is frequently influenced by environmental factors such as temperature. This study aimed to investigate the characteristics of temperature-sensitive rhinitis patients and to explore the effects of temperature on nasal symptoms. Methods: A cross-sectional study was conducted from February 2023 to February 2024 at Beijing Tongren Hospital, enrolling 5,595 adult outpatients with chronic rhinitis. Patients were diagnosed with AR or NAR, with AR further classified into seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR). Standardized questionnaires and serum-specific immunoglobulin E testing were performed. Nasal symptoms (congestion, itching, sneezing, and rhinorrhea) were assessed using a visual analogue scale. A generalized linear model with cubic spline functions was used to examine nonlinear associations between ambient temperature and nasal symptoms, adjusting for potential confounders. Associations between temperature sensitivity, symptom severity, and environmental exposures were analyzed. Results: A total of 83.6% of patients with AR and 84.5% of those with NAR reported temperature sensitivity. Patients sensitive to temperature changes had significantly higher nasal symptom scores than those insensitive to temperature changes ( P < 0.001). The proportion of temperature-sensitive individuals increased with the severity of chronic rhinitis symptoms. In SAR, symptoms exhibited an inverted U -shaped relationship with temperature, peaking around 20°C, which corresponded to the pollen peak. In PAR, low-temperature environments (<20°C) aggravated nasal congestion and were the main factor affecting quality of life. Conclusions: Temperature-sensitive rhinitis patients experience more severe nasal symptoms. Low-temperature environments have the greatest impact on patients with PAR, particularly exacerbating symptoms of nasal congestion. Temperature indirectly affects the nasal symptoms in SAR patients by influencing pollen exposure.

Background Pediatric eye diseases, especially myopia and other refractive errors as well as binocular vision disorders, have evolved into a pressing global public health concern. Effective caregiver-targeted eye health education is crucial for the early prevention and long-term management of these conditions. However, conventional educational approaches often struggle to deliver actionable and accessible guidance. Emerging artificial intelligence (AI) technologies, particularly large language models (LLMs), present novel opportunities to address this gap. Methods A mixed-methods design was conducted in this study. On one hand, a bibliometric analysis was conducted on publications related to pediatric eye health education from 2015 to 2025, using the Web of Science Core Collection and PubMed databases, with visualization implemented via Bibliometrix and CiteSpace software. On the other hand, a cross-sectional online questionnaire survey was administered to guardians of children aged 1–6 years to systematically assess their key concerns about pediatric eye diseases, knowledge levels, information sources, and preferences for educational formats. Results A total of 111 publications were included in the bibliometric analysis, which revealed a significant surge in research output after 2020. Traditional themes such as vision screening and patient education remained central, while AI- and LLM-related topics have emerged as recent research hotspots. China and the United States led in terms of publication volume, whereas several countries with lower output demonstrated higher average citation impact. Among 328 valid survey responses, guardians showed high concern for myopia, astigmatism, and strabismus but lacked sufficient practical knowledge regarding preventive pharmacological strategies and correct eye drop administration. Additionally, child-friendly, visualized, interactive, and online educational formats were strongly preferred. Conclusion By integrating bibliometric trends with the actual needs of caregivers, this study demonstrates that the growing role of AI and LLMs in pediatric eye health education reflects both technological advancement and unmet demands for personalized, actionable educational content. These findings provide an evidence-based foundation for the development of AI-driven pediatric eye health education tools, emphasizing the necessity of clinical oversight, ethical governance, and equitable access in future practice.

ABSTRACT Purpose To explore the ability of conjunctival microvasculature in differentiating ocular surface inflammation (OSI) in mild dry eye (DE), and to guide adjunctive anti-inflammatory treatment in mild DE. Methods 83 mild DE patients and 26 healthy controls were enrolled in a cross-sectional study. Mild DE patients were classified into those with OSI and those without based on Z-score level of tear cytokines. Differences in microvasculature and clinical manifestations were analyzed, alongside correlations with tear cytokines. A logistic regression model was developed for detecting OSI based on microvascular parameters. A secondary analysis of a RCT involved 35 mild DE patients with OSI to compare microvascular and clinical outcomes between treatment groups (adjunctive 0.05% Cyclosporine A vs. artificial tears alone). Results Elevated blood flow velocity (BFV: 0.37 ± 0.04 mm/s) and wall shear rate (WSR: 170.98 ± 26.96 s−1) were found in mild DE with OSI than those without (BFV: 0.32 ± 0.03 mm/s, WSR: 145.90 ± 18.46 s−1, p < 0.01), while no significant differences were found in clinical manifestations. BFV and WSR were correlated with IL-6 (rBFV = 0.43, rWSR = 0.39, p < 0.05). The AUC - ROC for the mild DE-related OSI detection model based on BFV and WSR was 0.858. In mild DE with OSI treated with 0.05% Cyclosporine A, BFV, WSR, IL-6, clinical manifestations improved significantly at 12 weeks (p < 0.05). Conclusions Elevated BFV and WSR can facilitate early detection of mild DE-related OSI before changes in symptoms and signs, allowing timely anti-inflammatory intervention.