Purpose: Allergic rhinitis (AR) is a pervasive global health problem, imposing a major economic burden and causing disability worldwide. Tongqiao-Biyan granule (TBG) has gained popularity in China for the treatment of AR. This study aimed to elucidate the molecular mechanism underlying TBG's efficacy in treating AR.

Methods: The Traditional Chinese Medicine pharmacological database was utilized to identify the main ingredients in TBG and their corresponding target genes. ARrelated target genes were identified using the GeneCards, OMIM, and DrugBank databases. The Gene Ontology (GO) network, Kyoto Encyclopedia of Genes and Genomes (KEGG), and target protein-protein interaction (PPI) network were employed to analyze the molecular mechanisms. The top five hub genes were selected for molecular docking with the top five ranked compounds to confirm their interaction in TBG when used in the treatment of AR.

Results: A total of 7 active ingredients from TBG, 784 predicted targets of TBG, and 945 AR targets were obtained. Analysis via the GO and KEGG databases revealed that TBG can act on AR by modulating inflammatory responses and promoting cell migration. PPI network analysis and molecular docking results suggested that phellopterin, quercetin, luteolin, denudatin B, and cleomiscosin A in TBG may alleviate the AR symptoms by interacting with key proteins such as TNF, AKT1, STAT3, VEGFA, and EGFR.

Conclusions: TBG modulates numerous targets across diverse signaling pathways in the AR therapy. Our results furnish a theoretical foundation for further exploring TBG's pharmacological mechanism in AR treatment.

Yes-associated protein (YAP), a pivotal protein of the Hippo signaling pathway, plays a crucial role in regulating cell proliferation and differentiation. Emerging evidence highlights its significance in respiratory inflammatory disorders, including chronic rhinosinusitis, allergic rhinitis. This review delves into the impact of YAP on individuals affected by these ailments, with a specific focus on the role it plays in nasal mucosal epithelial cells. We further explore the interplay between YAP and the inflammatory mediators, outlining the pathological mechanisms through which it contributes to tissue restructuring in these contexts. Despite advancements, gaps persist in understanding YAP's broader role in clinical applications. Future research directions are proposed in this article to bridge these knowledge gaps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by dysbiosis of nasal microbiota and dysregulation of the immune system. Macrophages are essential for protecting against infections, but their roles and mechanisms in CRSwNP are not fully understood. To date, we gradually recognize the heterogeneity of macrophages, and new subsets of macrophages have been identified at transcriptional level due to the development of single cell RNA-sequencing. In this review, we summarize the generation, polarization, phenotype identification, and function of macrophages in CRSwNP, providing a comprehensive understanding of macrophages in CRSwNP. Additionally, we also explore how macrophages interact with other cells, including epithelial cells, immune cells, and neurons, which can worsen inflammation. A better understanding of the role of macrophages could improve their ability to clear bacteria and reduce chronic inflammation in CRSwNP, which might be clinically beneficial for CRSwNP patients.

Purpose: This study aims to optimize experimental conditions to obtain a larger quantity of eosinophils from the type 2 inflammation mouse model, which will serve as a basis for further investigation into the role and mechanisms of eosinophils in type 2 inflammation.

Methods: We used a mouse model of type 2 inflammation and isolated potential eosinophil-resident tissues (bone marrow, spleen, and nasal mucosa) for flow cytometry analysis. By combining forward scatter, side scatter, and the cell population identified as CD45⁺ (protein tyrosine phosphatase receptor type C) CD11b⁺ (integrin alpha-M) Ly6G⁻ (lymphocyte antigen 6 family member G) Siglec-F⁺ (sialic acid-binding immunoglobulin-like lectin F), we characterized eosinophils.

Results: The results showed that the number and proportion of eosinophils in bone marrow were numerically higher compared to the spleen and nasal mucosa. Further exploration of conditions may provide guarantees for the later development of mechanism research.

Conclusion: These findings provide clues for further optimizing experimental conditions to obtain sufficient eosinophils from bone marrow for mechanistic studies. They also offer a potential framework for exploring phenotypic heterogeneity and functional studies of eosinophils in various tissues.

Uveitis, an intraocular inflammatory condition, can lead to significant visual impairment and is often associated with abnormal immune system activation. While vaccination stands as a pivotal defense against numerous infectious diseases, its safety and effectiveness in individuals with uveitis have come under heightened scrutiny. This concern arises from the potential impact of both the disease itself and immunosuppressive treatments on immune function. Several studies have drawn connections between various vaccines and the onset of uveitis, particularly hepatitis B, human papillomavirus, and influenza vaccines. Furthermore, though exceedingly rare, instances of intraocular inflammatory following COVID-19 vaccination have been documented, adding another layer of complexity. This review delves into the intricate relationship between vaccination and uveitis, assesses the vaccination risks for those afflicted, and explores the underlying mechanisms behind vaccine-induced uveitis. Finally, it offers recommendations for vaccination in uveitis patients and emphasizes the imperative for further investigation to unravel the complex dynamics between vaccines and uveitis, ultimately informing clinical practice.

Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder with variable manifestations, including recurrent epistaxis, telangiectasias, arteriovenous malformations, and family history. It is caused by heterozygous null alleles of ENG, ACVRL1, SMAD4, or BMP9, with delayed clinical diagnosis. Genetic testing is crucial for early diagnosis.

Objective: To analyze the variant distribution of HHT-related genes, expand variant databases for Chinese patients, and explore phenotype-genotype associations.

Methods: Thirty-two individuals from 20 unrelated families were recruited. Coding regions of ENG, ACVRL1, SMAD4, and BMP9 were sequenced. Variants were identified by sequence alignment. Epistaxis severity was evaluated using the epistaxis severity score (ESS), and the ESS differences between groups were analyzed using the Mann–Whitney test.

Results: Seventeen unique variants were identified in 17 unrelated HHT families (17/20, 85%), including 5 novel variants (3 in ENG and 2 in ACVRL1). Eleven ACVRL1 variants were identified in 12 families (12/17, 70.6%). Six variants of ENG were detected in 5 families (5/17, 29.4%), and one patient had two variants. ACVRL1 variants were 2.4 times more prevalent than ENG variants, with 41.7% of ACVRL1 variants in exon 10. A recurrent variant, c.1435C>T, was identified in two families. Epistaxis severity increased with age.

Conclusions: ACVRL1 variants were more common than ENG variants in Chinese HHT families, with exon 10 identified as a potential hotspot. These findings enhance understanding of HHT genetics and guide targeted genetic testing in China.

Background: Cataract, the leading cause of blindness worldwide, can significantly impair visual function.

Purpose: This study investigated the association between cataract-related falls among the elderly population in the Central region of Ghana.

Methods: The prospective cohort study among cataract patients aged 65 years and older, using purposive sampling to select facilities and consecutive sampling to recruit participants.

Results: The study achieved a 40% successful follow-up rate at 3 months post-surgery. Among the 500 older adult patients, 131 (26.2%) reported falls before undergoing cataract surgery. Of the 200 patients who had 24.0% falls pre-operatively, the prevalence of falls 3 months after surgical intervention was 16%. Demographics were not significantly associated with the risk of falling before cataract surgery (p > 0.05). However, participants with chronic conditions were 2.18 times more likely to fall than those without chronic conditions. Patients with hypertension (2.23 times) and diabetes (2.49 times) had higher risk of fall compared to those without these conditions. Additionally, patients with retinal conditions (2.86 times), and those with balance problems (1.86 times) were more prone to falling before surgical intervention than their counterparts without.

Conclusion: The study highlights the significant impact of cataract surgery in reducing fall prevalence among older adults.

Our ability to localize low-frequency sounds relies on interaural time differences (ITD), a sensitivity that is fundamental to our ability to pinpoint sound sources in azimuth and segregate competing sound sources across a wide range of situations. However, the neural representation of ITD has not been well characterized. This study aimed to elucidate distinctions in evoked cortical potentials and global functional connectivity during the unattended processing of sound localization on the horizontal plane, by recording and analyzing the auditory mismatch negativity (MMN) in adults, employing a deviant-standard oddball paradigm. A centrally-positioned sound source at the midline of the horizontal plane (ITD = 0 μs) served as the standard stimulus, while lateralized sounds with varying ITDs constituted the deviants. Results of MMN characteristics and the distribution of theta band power revealed a contralateral regulation mechanism of sound localization. To delve deeper into functional connectivity dynamics among different deviant stimulus groups, we computed the phase lag index within the theta band. Augmented functional connectivity was found between frontal electrode pairs when sound stimuli were directed towards the central compared to peripheral locations. In addition, assessments of global efficiency demonstrated that the peripheral sound stimuli revealed a higher global efficiency for peripheral sound stimuli. These observations suggest that smaller deviation from the center angle engages enhanced top-down attentional modulation to salient features. In summary, our results reinforced the contralateral regulatory mechanism governing sound source localization and illuminated the unique characteristics of theta band neural responses.

Background: GJB2 gene variants are the most important cause of sensorineural hearing loss. A large number of clinical studies have focused on coding region variants, and a significant proportion of patients with single coding region variants have unexplained clinical phenotypes. Current animal models consist mainly of conditional knockout mice and a small number of the mouse models with point variants.

Objective: To investigate the underlying deafness-inducing mechanisms in the mouse models with a point variant and compound heterozygous variants in noncoding region of the Gjb2 gene.

Method: The CRISPR-Cas9 technology was utilized to develop the mouse models carrying Gjb2 c.IVS1+1G>A variant. The Gjb2^IVS1+1G>A/WT mice were crossed with Cx26 conditional knockout mice (Gjb2^loxP/loxP; Rosa26^CreER) to obtain the Gjb2^{IVS1+1G>A/−} mice. Genotyping and Sanger sequencing were used to identify the mouse models. The change in hearing thresholds was detected by auditory brainstem response (ABR). Hair cells and spiral ganglion neurons (SGNs) were quantitatively estimated by using whole-mount cochlear preparations. Immunofluorescence staining was performed to observe the morphology of Cx26 gap junction plaques (GJPs) among cochlear supporting cells and monitor the accumulation of reactive oxygen species (ROS). A glucose analog was injected to assess the glucoseuptake capacity of outer hair cells.

Result: During the observation period, Gjb2^{IVS1+1G>A/−} mice showed late-onset hearing loss. At postnatal day 20 (P20), the Gjb2^{IVS1+1G>A/−} mice did not show significant loss of hair cells and SGNs. The Cx26 GJPs showed fragmentation. The ability of the outer hair cells to uptake glucose decreased, and the accumulation of ROS in the cochlea increased.

Conclusion: We speculated that fragmented GJPs leading to impaired materials supply and oxidative stress accumulation may contribute to hearing loss. Our study confirmed the pathogenicity of c.IVS1+1G>A variant and laid the foundation for explaining the clinical phenotype of patients.

Purpose: To explore the optimal surgical excision treatment for external auditory canal (EAC) cholesteatoma involving the posterior wall and partial mastoid process.

Methods: This study included 115 inpatients (152 ears) diagnosed with EAC cholesteatoma involving posterior wall and partial mastoid from April 2022 to April 2024. Each patient underwent a canal-wall-up mastoidectomy, canaloplasty, and tympanoplasty. Preoperative clinical symptoms and hearing were compared with postoperative outcomes during follow-ups.

Results: All patients achieved a dry-ear status and remained relapse-free over the 0.5-2 years' follow-ups. The most salient improvements were observed in hearing loss, oltagia, and aural fullness after the surgical intervention.

Conclusion: For EAC cholesteatoma with the posterior canal wall and partial mastoid invasion, canal-wall-up mastoidectomy with reconstruction of the posterior canal wall is preferable, provided there are no severely extensive cholesteatomas present in the mastoid.

Introduction: Nasal alar defects pose significant challenges due to the nose's central role in facial aesthetics and function. Various causes, including skin cancer resection, necessitate effective reconstruction techniques. Despite several available methods, identifying an ideal approach remains elusive.

Methods: This study introduces a single-stage reconstruction technique employing the nasolabial-folded-flap (NFL) with conchal cartilage support. A structured patient questionnaire evaluated functional and aesthetic outcomes, pain, healing and satisfaction. The survey involved six patients who underwent nasal reconstruction using this approach in 12 months.

Results: Patients expressed high satisfaction with functional and aesthetic outcomes. Functional aspects received very satisfactory ratings (mean 1.7), with aesthetically appealing results (mean 2). Reconstructed noses harmonized well with patients' faces (mean 2), with a moderate impact on daily activities (mean 2.7). Mild pain was occasionally reported (median 2.2) and healing was perceived as very successful (median 1.5). Patients were highly satisfied with care and support (median 1) and felt adequately informed (median 1.5). They strongly recommended this reconstruction technique to others (median 1).

Discussion: The NFL with conchal cartilage support proves versatile and cosmetically pleasing in single-stage reconstruction for full-thickness nasal alar defects. Patients demonstrated a strong willingness to recommend this approach to individuals with similar defects, showcasing its potential advantages. Despite limitations, our findings underscore the prospects of this technique in nasal reconstruction.

The nose is a structure of both cosmetic and functional importance. Cutaneous lesions of the nose occasionally represent a diagnostic challenge and involve the expertise of several specialties from dermatology, otolaryngology—head and neck surgery, infectious disease, and pathology, among others. We present a review of salient features of malignant and benign cutaneous nasal lesions which are of importance to physicians treating these complicated pathologies.

Uveitis, characterized by intraocular inflammation, has significant management challenges due to its diverse etiologies and complicated pathophysiology. The current first-line treatments primarily aim to calm inflammation with the underlying causes unaffected, often associated with systemic side effects, limited long-term efficacy, and disease recurrence. Gene therapies, as powerful therapeutic approaches, have been applied to treat various genetic and non-genetic diseases. However, the development of gene therapy for uveitis has been investigated less. This review discusses the possible targets and therapeutic approaches for uveitis gene therapy by analyzing some research examples in exogenous gene expression, RNAi, antisense therapy, and the CRISPR gene editing system. Furthermore, we discuss the limitations of listed gene therapies for uveitis and propose future research directions and potential strategies to overcome current challenges.

Background: Understanding the complex three-dimensional (3D) anatomy of the nasal cavity, paranasal sinuses, and skull base, is difficult but essential for otolaryngology trainees, especially for endoscopic techniques. There is no effective teaching tool at the junior resident or medical student level allowing visualization and manipulation of these structures in 3D.

Objective: To create an interactive 3D app modeling the sinus and skull base for use by junior trainees learning surgical anatomy.

Methods: Using Adobe Photoshop, Cinema 4D, and ZBrush, surgeon and medical illustration teams collaborated to develop a tool combining schematic representation of relevant anatomy with radiologic and endoscopic correlates. This was then incorporated into a web application. Twenty-one junior residents and medical students were recruited to use the app, and pre-and post-app self-assessments and experience surveys were conducted to assess didactic efficacy.

Results: We created an online-compatible fully manipulatable schematic 3D representation of the nasal cavity, paranasal sinuses, and anterior skull base that is capable of anatomic layering. This schematic is presented alongside representative de-identified radiologic images and surgical principles with corresponding highlighted diagrammatic structures to demonstrate clinically relevant radiologic and endoscopic anatomy. There was a statistically significant improvement in anatomical knowledge in all 13 questions assessing didactic efficacy, with 85.7% of participants providing overall positive feedback.

Conclusions: Acknowledging the didactic utility in an early validation study with junior trainees, this sinus anatomy teaching tool offers a low-cost and highly accessible modality capable of demonstrating complex anatomical relationships to trainees learning sinus and endoscopic endonasal skull base surgery.