Allergic rhinitis (AR) is a common immune-related disorder recently associated with gut microbiota (GM), though the underlying mechanisms remain unclear. This study employed Mendelian randomization (MR) to investigate causal relationships between GM and AR, combined with transcriptomic analyses, including both bulk and single-cell RNA sequencing (scRNA-seq), to explore molecular mechanisms at tissue and cellular resolutions. Data for AR and GM were sourced from public databases. MR identified causal microbial taxa, whose associated SNPs were mapped to genes. These were intersected with differentially expressed genes (DEGs) from transcriptomic data to identify candidate genes. Key genes were validated through expression analysis, immune infiltration, functional enrichment, regulatory network prediction, drug screening, and molecular docking. Single-cell RNA sequencing was used to identify key cell types and pseudotime trajectories. MR analysis identified 29 GM taxa causally linked to AR. For instance, family.Porphyromonadaceae.id.943 was protective, while genus.unknowngenus.id.1000006162 was a risk factor. SNP-based gene mapping yielded 246 genes, which overlapped with 1329 DEGs to identify INPP5D and KIF16B as key genes. These were enriched in pathways such as ribosome, peroxisome, and systemic lupus erythematosus. Immune infiltration revealed altered abundances of natural killer T cells and activated CD4 + T cells. Single-cell analysis highlighted Th1 cells as central to AR pathogenesis, with stable expression of INPP5D and KIF16B during Th1 differentiation. This study establishes a causal link between GM and AR and identifies INPP5D and KIF16B as potential key genes, with Th1 cells as a critical immune subset, providing new insights into AR's molecular mechanisms.

This systematic review evaluates the efficacy and benefit of cartilage conduction hearing aids (CC-HAs) and that factors that influence purchasing decisions. The hearing thresholds and functional gain following CC-HA wear were synthesised. A one-way analysis of variance compared the differences in the hearing thresholds and functional gain at individual frequencies and in patients with a variety of pathological changes. The synchronised aided hearing threshold and functional gain at 2.0 kHz were significantly better than at 0.5, 1.0, and 4.0 kHz. There was no significant difference in the synchronised unaided hearing thresholds across individual frequencies between 0.5 and 4.0 kHz. The synchronised functional gain in patients with atresia was significantly greater than in patients with aural atresia or stenosis and middle ear pathologies with normal ear canals. The acceptability of CC-HAs in terms of purchase decision is influenced by the condition of the external auditory meatus and severity of hearing loss, with the highest purchase rate seen in patients with aural atresia or stenosis. CC-HAs’ fitting procedure advantages and cosmetic considerations make these devices a viable and preferred choice for individuals with microtia and aural atresia. Additional research to evaluate the benefits towards emotional well-being is crucial to gain insights into the psychological impact of CC-HA use.

Background: Deafness autosomal dominant 2A (DFNA2A) is related to non‐syndromic genetic hearing impairment. The KCNQ4 (Potassium Voltage‐Gated Channel Subfamily Q Member 4) can lead to DFNA2A. In this study, we report a case of autosomal dominant non‐syndromic hearing loss with six family members as caused by a novel variant in the KCNQ4 gene.Methods: The whole‐exome sequencing (WES) and pure tone audiometry were performed on the proband of the family. Sanger sequencing was conducted on family members to determine if the novel variant in the KCNQ4 gene was present. Evolutionary conservation analysis and computational tertiary structure protein prediction of the wild‐type KCNQ4 protein and its variant were then performed. In addition, voltage‐gated channel activity of the wild‐type KCNQ4 protein and its variant were tested using whole‐cell patch clamp.Results: It was observed that the proband had inherited autosomal dominant, non‐syndromic sensorineural hearing loss as a trait. A novel co‐segregating heterozygous missense variant (c.902C>A, p.Ala301Asp) of the KCNQ4 gene was identified in the proband and other five affected family members. This variant was predicted to cause an alanine‐to‐aspartic acid substitution at position 301 in the KCNQ4 protein. The alanine at position 301 is well conserved across different species. Whole‐cell patch clamp showed that there was a significant difference between the WT protein currents and the mutant protein currents in the voltage‐gated channel activity.Conclusion: In the present study, performing WES in conjunction with Sanger sequencing enhanced the detection of a novel, potentially causative variant (c301 A>G; p.Ala301Asp) in exon 6 of the KCNQ4 gene. Therefore, our findings contributed to the mutation spectrum of the KCNQ4 gene and may be useful in the diagnosis and gene therapy of deafness autosomal dominant 2A.