2025-09-15 2025, Volume 2 Issue 3

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  • REVIEW ARTICLE
    Lianqi Wan , Luo Zhang , Yingshi Piao , Yuan Zhang
    2025, 2(3): 151-163. https://doi.org/10.1002/eer3.70018

    IgG4-related chronic rhinosinusitis (IgG4-related CRS) is gaining recognition among various specialized physicians. As a systemic disease involving multiple organs, IgG4-related CRS is still not widely recognized as an independent clinical entity. Given the complexity of diagnosing autoimmune-related multisystem diseases, early recognition and diagnosis of IgG4-related CRS have become more challenging. Despite being an independent clinical entity, IgG4-related CRS is still mainly understood only by otolaryngologists but not other specialists. Here we reviewed studies related to the gradual recognition, the diagnostic controversies and challenges, treatment progress, pathogenesis, and current knowledge of IgG4-related CRS.

  • REVIEW ARTICLE
    Xintong Li , Jingjing Guo , Jing Song , Ming Wang
    2025, 2(3): 164-172. https://doi.org/10.1002/eer3.70023

    Epithelial cell-derived thymic stromal lymphopoietin (TSLP) plays a crucial role in mediating type 2 immune responses, which is one of the key underlying patho-physiological mechanisms of allergic rhinitis (AR) and most presentations of chronic rhinosinusitis with nasal polyps (CRSwNP). Researches show that inhibiting TSLP signaling has significant therapeutic potential in alleviating type 2 inflammation. Biologics targeting TSLP have been developed and introduced into clinical practice, yielding promising therapeutic outcomes, especially in asthma. Several anti-TSLP antibodies are undergoing clinical trials to investigate the efficacy and safety in treating CRSwNP and AR. This review aims to delve into the latest progress regarding the functional role of TSLP, the clinical outcomes associated with antiTSLP therapies, and the therapeutic potential of anti-TSLP antibodies in treating nasal type 2 inflammation.

  • RESEARCH ARTICLE
    Hongqiang Chen , Zhe Zhang , Xueting Yang , Chao Li
    2025, 2(3): 173-184. https://doi.org/10.1002/eer3.70014

    Background: Nasopharyngeal carcinoma (NPC) is a prevalent malignant tumor of the head and neck, characterized by a complex pathogenesis. Most newly diagnosed NPC patients are locally advanced, and 20%–30% of advanced NPC patients have poor immunotherapy results.

    Purpose: This study aimed to identify key genes associated with immunity and programmed cell death (PCD) in NPC, thereby providing new targets and strategies for precision treatment.

    Results: In this study, functional annotation and pathway enrichment analysis of differentially expressed genes (DEGs) of GSE12452 and GSE61218 was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Moreover, the search tool for the retrieval of interaction gene/proteins database was constructed to establish a protein-protein interaction (PPI) network to screen key genes. From GSE12452 and GSE61218, 700 and 619 DEGs were obtained, respectively, and 346 common differential expressed genes (co-DEGs) were screened. Furthermore, 24 immune-related common differential expressed genes (IDEGs) were screened by the interaction of co-DEGs with immune-related DEGs. The major GO functions enriched for IDEGs were chemokine activity and receptor binding, and KEGG pathways were enriched for cytokine-cytokine receptor interactions, IL-17 signaling pathway, chemokine signaling pathway, and so on. PPI analysis identified seven hub genes, including interferon-gamma (IFNG), CXCL11, CCL8, IL33, Prostaglandin-endoperoxide synthase 2 (PTGS2), CXCL3, and CXCL14. Remarkably, IFNG and PTGS2 may be the key targets for PCD regulation of NPC immunity.

    Conclusion: Our results suggest that IFNG and PTGS2 are expected to be new markers and targets for the diagnosis and treatment of NPC, which opens a new way to further improve the prognosis of NPC patients.

  • RESEARCH ARTICLE
    Qian Wan , Ruotong Wang , Yaqin Wu , Dongzhen Yu , Haibo Shi , Jingjing Wang , Pengjun Wang , Zhengnong Chen
    2025, 2(3): 185-193. https://doi.org/10.1002/eer3.70019

    Background: Vestibular schwannomas (VS) are the most common tumors in the cerebellopontine angle, which can lead to hearing loss, particularly following tumor resection. For patients with bilateral VS associated with neurofibromatosis type 2 (NF2), hearing loss significantly undermines their quality of life.

    Objective: This study aims to evaluate the outcomes of ipsilateral cochlear implantation (CI) in patients with VS.

    Method: We assessed six patients with VS, three of whom were diagnosed with NF2. Four patients underwent VS resection combined with simultaneous ipsilateral CI. Two patients received CI without tumor removal. Electrically evoked auditory brainstem response (eABR) testing was employed to assess the functionality of the cochlear nerve during the resection procedure.

    Results: Simultaneous ipsilateral CI following VS resection was performed in four patients who underwent tumor removal, and cochlear nerve function was identified using eABR testing. Two patients without tumor resection also had implantations. The average impedance of the test electrodes was within the normal range and neural telemetry responses were detected in all patients. One patient opted out of using the cochlear due to normal hearing in the contralateral ear and found the implant unbeneficial. The remaining five patients experienced improvements in hearing, albeit to varying degrees.

    Conclusion: Simultaneous ipsilateral CI after VS resection is an effective approach for auditory rehabilitation. For NF2 patients with small, stable tumors, CI without tumor removal can also be considered a viable option. This study highlights the potential of CI in hearing rehabilitation for patients with VS, particularly those with NF2.

  • RESEARCH ARTICLE
    Yu Song , Minghang Yu , Yuan Zhang , Xi Wang , Xiangyi Liu
    2025, 2(3): 194-201. https://doi.org/10.1002/eer3.70020

    Background: Chronic rhinosinusitis (CRS), characterized by persistent inflammation of the nasal and sinus mucosa, exhibits an escalating global prevalence and incidence. Interleukin-8 (IL-8), a key chemokine driving neutrophil recruitment, is implicated in CRS pathogenesis. While non-epigenetic mechanisms of IL8 regulation have been reported, the epigenetic landscape governing IL8 expression in CRS remains unexplored.

    Objective: This study aimed to investigate the epigenetic regulation of IL-8 expression in human nasal epithelial cells (HNEpCs) with a focus on histone modification-mediated mechanisms.

    Methods: Tumor necrosis factor-alpha (TNF-α) was selected as a prototypical pro-inflammatory stimulus through systematic screening. An in vitro model of IL-8 induction was established and validated in TNF-α-treated HNEpCs. Regulatory mechanisms were probed using bioinformatics tools (UCSC Genome Browser, Cistrome DB) and pharmacological inhibitors targeting histone-modifying enzymes. siRNA-mediated enhancer of zeste homolog 2 (EZH2) knockdown to assess its regulatory role in IL-8 expression; Chromatin Immunoprecipitation followed by quantitative PCR (ChIP-qPCR) to determine whether H3K27me3 is directly enriched at the IL8 promoter region under TNF-α stimulation.

    Results: TNF-α stimulation induced time and concentration-dependent upregulation of IL-8 mRNA (p < 0.001) and protein secretion (p < 0.001) in HNEpCs. TNF-α-mediated IL-8 upregulation was abrogated by the addition of methyl-transferase inhibitors EPZ005687, EPZ6438, and BIX01294. SiRNA-mediated EZH2 depletion significantly enhanced both IL-8 mRNA (p < 0.001) and protein levels (p < 0.01). ChIP-qPCR confirmed TNF-α-dependent enrichment of H3K27me3 at the IL8 promoter, supporting EZH2-mediated transcriptional repression.

    Conclusion: EZH2-dependent H3K27 trimethylation is a key epigenetic mechanism controlling IL-8 gene expression in HNEpCs.

  • RESEARCH ARTICLE
    Yan Wang , Xiaoyu Song , Fengxin Yang , Huhuifen He , Kun Zhao , Jingjing Qiu , Limei Cui , Qiang Zhang , Limei Liu , Yan Sun
    2025, 2(3): 202-214. https://doi.org/10.1002/eer3.70021

    Background: To explore the material basis and action mechanism of the chemical component gene of pepper on presbycusis, and to provide a reference for the traditional Chinese medicine treatment of age-related hearing loss (ARHL).

    Methods: The chemical composition and action targets of traditional Chinese medicine flavor of pepper were searched using the Traditional Chinese Medicine System Pharmacological database. Disease targets for ARHL were identified through the GeneCards database. The interaction relationship of the “drug-component-target-pathway” network and potential targets were constructed using Cytoscape software, and the mechanism of action was predicted by enrichment analysis.

    Results: As a result, 6 active components, 36 drug targets and 1100 disease targets of presbycusis were excavated, and 26 drug-disease common targets were obtained, with the key targets including CTNNB1, GSK-3β, GJA1, AKT1, MYC, BCL2. A total of 254 entries were obtained by GO enrichment analysis, which mainly involved neuronal apoptotic process, apoptotic process, and extracellular signalling process. KEGG pathways were enriched to select 72 signal pathways, including P53 signaling pathway, comprehensive cancer pathway, TNF-α signaling pathway, neurodegenerative disease regulatory pathway, cell apoptosis pathway, etc. The molecular docking results showed that the folic acid (FA) family has a good binding ability with GSK-3β.

    Conclusions: In conclusion, capsicum may exert a suppressive effect on the occurrence and progression of ARHL through multiple pathways. Its main component, FA, demonstrates a strong binding affinity with GSK-3β, suggesting that it could serve as a potential therapeutic target for presbycusis.

  • RESEARCH ARTICLE
    Abdallah Jonas , Denis Katundu , Johnson Shayo , Petro Nsalu , Ezekiel Karuga , Kajiru Kilonzo , Peter Shija
    2025, 2(3): 215-220. https://doi.org/10.1002/eer3.70022

    Background: Hearing loss, affecting 20% of the global population, disproportionately impacts low- and middle-income countries, including Africa. Sensorineural hearing loss (SNHL) is prevalent among hemodialysis patients. In Tanzania, the growing number of hemodialysis patients highlights the need for hearing assessments. Previous studies may have underestimated hearing loss prevalence by excluding key comorbidities like diabetes and hypertension.

    Aim: To determine the prevalence, severity, and associated factors of hearing loss among patients undergoing hemodialysis at Kilimanjaro Christian Medical Center (KCMC).

    Methods: This analytical hospital-based cross-sectional study was conducted at KCMC using a convenient sampling technique. Demographic and clinical data, including histories of renal disease, diabetes, hypertension, HIV, autoimmune diseases, and medication use, were collected via a structured questionnaire. Basic audiological assessments were performed using a pure-tone audiometer. Data were analyzed using univariate and multivariate logistic regression with IBM SPSS Statistics (version 25).

    Results: Bilateral SNHL was observed in 38.2% of patients, with 57.2% experiencing mild hearing loss, 35.7% moderate hearing loss, and 7.1% moderately severe hearing loss. Factors associated with hearing loss included advanced age (>60 years), longer duration on hemodialysis, hypertension, and diabetes mellitus.

    Conclusion: Mild bilateral SNHL was prevalent among hemodialysis patients. Key factors contributing to hearing loss were older age, prolonged hemodialysis, diabetes, and hypertension. Implementing a protocol for regular hearing assessments in this population is essential.

  • RESEARCH ARTICLE
    Fa Zhang , Yan Li , Xiwei Zhang , Zhaoyang Wang , Boshizhang Peng , Mengxiao Wu , Shaoyan Liu , Dangui Yan , Zongmin Zhang , Changming An
    2025, 2(3): 221-230. https://doi.org/10.1002/eer3.70024

    Background: Postoperative drainage management and hypocalcemia monitoring are critical factors influencing enhanced recovery after surgery (ERAS) following thyroidectomy. This study aimed to evaluate the effects of different drainage pressures on postoperative drainage volume and hospitalization duration, and to explore the predictive value of parathyroid hormone (PTH) levels for hypocalcemia. The goal was to develop a multidimensional ERAS strategy for thyroid cancer patients.

    Methods: This prospective randomized controlled trial enrolled 211 patients undergoing thyroidectomy. Participants were randomly allocated into three groups based on drainage pressure. Postoperative drainage volume, hospitalization duration, and complications were recorded. For patients undergoing total thyroidectomy, PTH and serum calcium levels were measured postoperatively. The optimal PTH cut-off value was determined using receiver operating characteristic curve analysis.

    Results: The low-pressure group exhibited significantly reduced postoperative drainage volume on day 1 (6.54 ± 9.53 mL) compared to the medium- and highpressure groups (34.07 ± 19.05 mL and 32.41 ± 20.72 mL). Drainage removal time (1.06 ± 0.23 days) and hospitalization duration (1.26 ± 0.47 days) were also shorter in the low-pressure group. A postoperative 2-h PTH level ≤ 6.985 pg/mL effectively predicted hypocalcemia (sensitivity 79.4%, specificity 91.0%). The combined ERAS protocol further reduced hospitalization duration and significantly lowered postoperative Visual Analog Scale scores (0.85 ± 0.75) without increasing complication rates.

    Conclusion: Low-pressure drainage reduces postoperative drainage volume and accelerates recovery in thyroid cancer patients. A 2-h postoperative PTH level ≤ 6.985 pg/mL serves as a reliable predictor for hypocalcemia. The combined strategy of optimized drainage pressure and PTH monitoring provides a safe and effective ERAS pathway for thyroid surgery.

  • CASE REPORT
    Grant Gochman , Danae Alexandrou , Amy Pittman
    2025, 2(3): 231-233. https://doi.org/10.1002/eer3.70025