BackgroundHereditary hearing loss demonstrates significant genetic heterogeneity, involving diverse genes and variation types. Autosomal dominant forms present particular challenges in variant interpretation due to variable expressivity.ObjectivesThis study aimed to clinically and molecularly characterize a multi-generational family with autosomal dominant hereditary hearing loss, and to functionally validate the pathogenicity of an identified novel variant.MethodsComprehensive clinical evaluations included audiometric testing and medical history review. Genetic analysis employed whole-exome sequencing followed by Sanger validation. Functional characterization involved minigene splicing assays and transcript analysis to assess the impact on splicing mechanisms.ResultsAffected individuals exhibited post-lingual, bilateral, symmetric, progressive sensorineural hearing loss, initially affecting high frequencies. We identified a novel GSDME mutation (NM_001127453.2:c.1123G>T; p.Glu375Ter) that disrupts an exon splicing enhancer, causing exon 8 skipping and frameshift alterations. Functional assays confirmed reduced enhancer activity and aberrant splicing. Literature review of 20 reported mutations revealed substantial phenotypic variability and highlighted limitations of splice prediction algorithms.ConclusionsOur findings expand the GSDME mutation spectrum and provide functional evidence supporting a pathogenic role for non-sense variants through splicing disruption mechanisms. This study reinforces the potential gain-of-function hypothesis for GSDME-associated hearing loss and emphasizes the necessity of functional validation for accurate variant interpretation.

The stria vascularis is a key structure in the inner ear responsible for generating and maintaining the endocochlear potential (EP), and its dysfunction is closely associated with various forms of hearing loss. The stria vascularis is composed of marginal cells, intermediate cells, and basal cells, among which marginal cells play a central role in the generation and maintenance of the EP. Therefore, establishing an in vitro primary culture model of marginal cells is essential for investigating the biological characteristics of the stria vascularis and its involvement in hearing loss-related disorders. In this study, we successfully isolated and cultured primary marginal cells from the stria vascularis of neonatal mice. Strial tissues were obtained by microdissection, digested with type II collagenase, and purified by differential plating to remove most fibroblasts, with cultured cells reaching over 80% confluence by day 7. Immunofluorescence staining demonstrated stable expression of cytokeratin 18 (CK18) and potassium voltage-gated channel subfamily Q member 1 (KCNQ1), confirming successful isolation, high purity, and preserved physiological function of marginal cells. Based on this model, in vitro oxidative stress and cellular senescence models were established using hydrogen peroxide (H2O2) and D-galactose, respectively. Treated cells exhibited significantly increased intracellular reactive oxygen species (ROS) levels and senescence-associated β-galactosidase (SA-β-gal) positivity, indicating high sensitivity of primary marginal cells to oxidative stress and senescence-inducing stimuli. Collectively, this study establishes a stable and reproducible system for the culture and modeling of mouse primary marginal cells, providing a reliable in vitro platform for investigating stria vascularis dysfunction and related mechanisms.

Hereditary carotid body tumor (HCBT) is a rare neuroendocrine tumor mainly caused by germline mutations of the SDHx gene. Its multifocality, familial aggregation, and potential malignant risk pose unique challenges to diagnosis and treatment. This review systematically expounds the molecular mechanism of HCBT, pointing out that SDHx mutations drive tumorigenesis through the “pseudo-hypoxia” pathway and are regulated by epigenetic and somatic mutations. In terms of diagnosis, we emphasize the crucial role of 68Ga-DOTATATE PET/CT and SDHB immunohistochemistry and advocate for multigene panel sequencing for patients with high-risk characteristics (such as early-onset, multifocal, family history or malignant signs) to clarify the genetic background. On the basis of existing evidence, we recommend conducting baseline biochemical tests for all newly diagnosed patients and actively suggest genetic screening for high-risk individuals such as those who are young, have multifocal tumors, or have a family history. In terms of treatment, surgery is the main treatment method for HCBT. Nevertheless, individualized strategies still need to be formulated based on tumor classification and patient’s overall condition and genetic background. Comprehensive management measures such as targeted therapy, radionuclide therapy, and standardized family management are crucial for improving the prognosis of patients.

Microplastics (MPs) are ubiquitous environmental pollutants, yet their neurotoxic effects on the auditory system remain poorly understood. This study develops an integrated multi-level analytical framework combining auditory neurophysiology, behavioral assessment, tissue biochemistry, transcriptomics, and proteomics to investigate polystyrene (PS)-MPs-induced auditory neurotoxicity in rats. PS-MPs infiltrate the auditory system and significantly impair auditory processing, with central dysfunction emerging earlier and more prominently than peripheral alterations. Multi-omics analyses reveal coordinated suppression of glutamatergic synapse and Wnt signaling pathways in the cochlear nucleus. Mechanistically, PS-MPs perturb the crosstalk between glutamatergic synaptic and Wnt signaling, promoting AMPA receptor (AMPAR) internalization and potentially affecting synaptic plasticity-related processes and neuronal responsiveness. In parallel, PS-MPs trigger oxidative stress, apoptosis, and glial activation, reflecting pronounced neuroinflammatory and redox imbalance. In primary cochlear nucleus neurons (PCNNs), these mechanisms were further validated in vitro, where activation of Wnt signaling by Wnt3a significantly alleviated oxidative injury and reduced AMPAR internalization. Collectively, these findings provide comprehensive preclinical evidence for the neurotoxic potential of MPs and reveal a previously unrecognized PS-MPs-induced auditory neurotoxicity, although further studies are needed for human relevance. Results from the rat model further implicate Wnt-mediated signaling as a potential modulatory pathway underlying MPs-induced synaptic molecular alterations and redox dysfunction.

Background Basophils are key targets in allergic diseases. Omalizumab blocks IgE binding to FcεRI on basophils, reducing allergic responses. The basophil activation test aids allergy diagnosis, but their role in allergic rhinitis (AR) remains unclear. We assessed omalizumab's impact on basophil reactivity and its clinical associations in moderate-to-severe AR. Objective This study aimed to determine the predictive value of CD203c and CD63 as basophil activation markers for clinical response to omalizumab in patients with moderate-to-severe allergic rhinitis. Methods We collected and analyzed clinical symptoms and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores of 27 patients with moderate-to-severe AR who were treated with omalizumab for more than 12 weeks. Patients were divided into a non-basopenic group (OMA-AR/NB) and a basopenic group (OMA-AR/B) based on peripheral blood basophil counts (basopenic: <8000 cells/mL). FcεRI, CD63, and CD203c expression on blood basophils induced by stimulant were measured at baseline and at 12 weeks after omalizumab treatment using flow cytometry. Results The RQLQ score in OMA-AR/NB decreased from 33.0 ± 11.0 at baseline to 5.2 ± 4.2 at 12 weeks, while in OMA-AR/B, the score decreased from 33.8 ± 7.6 at baseline to 19.4 ± 5.9 at 12 weeks. Additionally, the basophil activation assay yielded the best classification accuracy (73.97% sensitivity, 88.89% specificity, cut-off value: 8.0%) for %CD203c+ in patients with AR. Conclusion During omalizumab treatment in patients with AR, CD203c was a more suitable marker for the basophil activation test (BAT). Furthermore, %CD203c+ > 8.0%, combined with a normal basophil count at baseline, could be used to predict the therapeutic effect of omalizumab.

Background Stem cell therapy offers promise for the neurodegenerative diseases and has been explored for sensorineural hearing loss (SNHL). However, effective cell delivery strategies remain a critical challenge for SNHL treatment.Methods To address this need, we established an ouabain-induced SGN injured hearing loss model in rat and evaluated a novel transplantation strategy targeting the cochlear nerve surface via posterior occipital approach, designed to minimize cochlear structural damage and facilitate targeted cell delivery to Rosenthal's canal (RC). The temporal changes in glial cell densities within RC revealed a progressively deteriorating neural microenvironment, supporting early-stage intervention. Accordingly, hair follicle-derived neural crest stem cell (HFNCSC) transplantation was performed 3 or 4 days after modeling via two approaches: cochlear nerve surface transplantation (CNT) and round window transplantation (RWT).Results CNT resulted in significant improvements in auditory function, as evidenced by reduced auditory brainstem response (ABR) thresholds, shortened wave I latencies, and preserved wave I amplitudes post-transplantation. Transplanted cells were distributed along the nerve trunk and within RC. In contrast, RWT failed to improve auditory function and caused cochlear structural damage, with widespread cell dispersion in cochlear fluids. Notably, the CNT group exhibited significantly higher densities of TUJ1-positive neuron-like cells and glial cells in the RC, accompanied by enhanced myelin basic protein expression suggestive of remyelination. No such improvements were observed in the RWT group.Conclusions These findings suggest that cochlear nerve surface transplantation enhances stem cell survival and auditory function recovery, and represents a promising delivery approach for stem cell-based therapy of SGN-related hearing loss.

Background: Patients with moderate-to-severe allergic rhinitis (AR) often experience a heavy clinical burden and require more medications to alleviate nasal symptoms. The aim of this study was to evaluate the efficacy and safety of GSP301, a fixed-dose combination nasal spray containing olopatadine hydrochloride and mometasone furoate, in patients with seasonal AR (SAR). Methods: In this multicenter, randomized, double-blind, parallel-group study, moderate-to-severe SAR patients were assigned at a 1:1:1 ratio to receive intranasal GSP301, olopatadine hydrochloride (OLO), or mometasone furoate (MF) for 14 days. The primary endpoint was the change from baseline in the average A.M. and P.M. 12-hour reflective total nasal symptom score (rTNSS). Secondary endpoints included changes in the instantaneous TNSS (iTNSS), individual nasal symptoms, reflective total ocular symptom score (rTOSS), instantaneous total ocular symptom score (iTOSS), individual ocular symptoms, and rhinoconjunctivitis quality-of-life questionnaire (RQLQ). Exploratory endpoints and adverse events were also analyzed. Results: Among the 534 subjects, the GSP301 group demonstrated statistically significant improvements in the average rTNSS compared with the OLO group [posterior least square mean difference (LSMD) =-0.56; P < 0.0001] and the MF group (posterior LSMD =-0.43; P < 0.0001). Consistent benefits were observed across secondary endpoints, including iTNSS, rTOSS, RQLQ, and individual nasal and ocular symptoms (all P < 0.05). Additionally, GSP301 reduced the levels of interleukin (IL)-5 and eosinophilic cationic protein (ECP) in nasal secretions. Treatment-emergent adverse events (TEAEs) occurred in 11.2%, 13.5%, and 11.3% of patients in the GSP301, OLO, and MF groups, respectively. Conclusion: Compared with OLO and MF, GSP301 demonstrated superior efficacy, safety, and potential advantages in alleviating local inflammation in patients with moderate-to-severe SAR.

OBJECTIVES:To assess the demographic and clinical characteristics, treatment and health outcome, and economic burden of juvenile-onset recurrent respiratory papillomatosis (JoRRP) in China. METHODS:We identified twelve hospitals mainly responsible for JoRRP management across China to enroll patients presenting for JoRRP between Jan 1, 2011, and Dec 31, 2021. Data were primarily extracted from medical records, and missing values were additionally collected through telephone or outpatient interviews by two researchers independently. We used counts (proportions) and median values (interquartile range, IQR) to describe data. We applied the Lorenz curve and the concentration index (C-index) to indicate the wealth-related and education-related inequalities in JoRRP. RESULTS:Of the 361 enrolled JoRRP patients, the median age at first diagnosis was 2.7 years (IQR: 1.5-5.0). During the 7.2-year median follow-up, we observed that 314 (87.0%) patients experienced relapse and 125 (38.0%) patients underwent an aggressive clinical course. The median value for the estimated total economic costs per patient was 8717.5$ (IQR: 4700.6$-15359.1$) and the occurrence of catastrophic health expenditure was concentrated in families with low incomes and less-educated parents. CONCLUSION:Chinese JoRRP patients experienced significant disease burden characterized by severe clinical symptoms and substantial economic costs. Strategic healthcare plans for JoRRP are needed for disease mitigation in China.

OBJECTIVES:To assess the demographic and clinical characteristics of Chinese adult-onset recurrent respiratory papillomatosis (AoRRP) and analyze the influence of age at diagnosis on recurrence. METHODS:Histologically confirmed AoRRP cases from 10 tertiary hospitals across China's 7 regions from 2011 to 2021 were analyzed. Demographic and clinical characteristics were summarized, recurrence probabilities (1-, 3-, 5-, and 7-year) were estimated by the Turnbull method, and early-course recurrence trajectories were identified using growth-mixture modelling (GMM). Associations between diagnostic age and recurrence were assessed using a generalized log-rank test, multivariable zero-inflated negative binomial regression, gamma regression, and multivariable logistic regression. RESULTS:Chinese AoRRP was diagnosed at a median age of 38 years, with peaks at 29 and 53 years; males accounted for 81.54% of cases. Hoarseness was the leading presenting symptom (85.54%). The median follow-up was 8.79 years (IQR = 5.50-11.23). Severe outcomes were observed, including aggressive AoRRP (9.85%), malignant transformation (2.46%), and mortality (0.62%). Overall, 65.85% of patients had at least one recurrence, and the recurrence density was 224.17 per 1,000 person-years. Of the four early-course recurrence trajectories identified by GMM, the persistent (18.75%) and early-burst (12.81%) types displayed frequent recurrences shortly after diagnosis. In multivariable analysis, each additional diagnostic year reduced the total number of recurrences (IRR = 0.97, 95% CI = 0.95-0.98) and made the early-course trajectory less severe (Persistent: OR = 0.89, 95% CI = 0.85-0.93; Early-Burst: OR = 0.91, 95% CI = 0.87-0.96). CONCLUSIONS:Chinese AoRRP patients showed a bimodal age at diagnosis. Recurrence exhibited marked heterogeneity, with the number and pattern of relapses varying widely among patients. Overall, a younger age at diagnosis was consistently linked to a substantially heavier recurrence burden.

Diabetic foot ulcers (DFUs) are a severe complication of diabetes, characterized by impaired wound healing, chronic inflammation, and tissue degradation. N6-methyladenosine (m6A), has emerged as a critical regulator in gene expression and cellular function in wound healing. This study aimed to systematically investigate the role of methylation-related genes (MRGs) in DFU pathogenesis, focusing on their diagnostic and therapeutic potential through integrative multi-omics analysis and experimental validation. Publicly available bulk RNA-seq, microarray, and single-cell RNA sequencing (scRNA-seq) datasets were analyzed to identify differentially expressed MRGs (DE-MRGs). Machine learning algorithms (LASSO, GBM, SVM-RFE, Random Forest) were used to screen key biomarkers. Immune infiltration and pathway enrichment analyses characterized inflammatory signatures, while scRNA-seq mapped MRG dynamics across cell types. Functional assays validated the role of METTL16 in high glucose-treated human skin fibroblasts (HSFs), assessing collagen synthesis, oxidative stress, and cellular migration. Thirteen DE-MRGs were identified in DFU tissues, with METTL16, NSUN3, and IGF2BP2 prioritized as diagnostic biomarkers. Immune profiling revealed M1 macrophage enrichment and dysregulated IL-17/MAPK pathways. Single-cell analysis highlighted METTL16's dynamic role in fibroblast activation and intercellular communication. Cell-based experiments confirmed the protective effects of METTL16 in HSFs, including enhanced migration, restored collagen synthesis, and reduced oxidative stress under hyperglycemic conditions. This study systematically identifies MRGs as critical regulators in DFU pathogenesis, with METTL16 emerging as a promising diagnostic biomarker and therapeutic target. The findings provide novel insights into the molecular mechanisms underlying DFU progression and offer potential avenues for improved diagnostic tools and therapeutic strategies.

Objective:To explore strategies for preserving facial nerve function during surgeries for rare tumors of the internal auditory canal. Methods:A total of 235 cases of internal auditory canal tumors treated between 2010 and 2023 were included, encompassing vestibular schwannomas, cavernous hemangiomas, meningiomas, and other rare tumors. Various data, including clinical presentations, imaging classifications, and treatment processes, were meticulously analyzed to delineate the characteristics of rare tumors and assess pre-and postoperative facial nerve function. Results:Among all internal auditory canal tumors, vestibular schwannomas accounted for 91.9%. In rare tumors, facial nerve schwannomas constituted 5.3%, cavernous hemangiomas 26.3%, meningiomas 15.8%, and arterial aneurysms 10.5%. Significantly, patients with cavernous hemangiomas displayed pronounced invasion of the facial nerve by the tumor, in contrast to other tumor types where clear boundaries with the facial nerve were maintained. During surgery, individualized approaches and strategies for facial nerve protection were implemented for different tumor types, involving intraoperative dissection, tumor excision, and facial nerve reconstruction. Conclusion:Preservation of the facial nerve is crucial in the surgical management of rare tumors of the internal auditory canal. Accurate preoperative diagnosis, appropriate timing of surgery, selective surgical approaches, and meticulous intraoperative techniques can maximize the protection of facial nerve function. Personalized treatment plans and strategies for facial nerve functional reconstruction are anticipated to enhance surgical success rates, reduce the risk of postoperative facial nerve dysfunction, and ultimately improve the quality of life for patients.

Introduction: The incidence of allergic rhinitis (AR) is increasing year by year, and the pathogenesis is complex, in which diet may play an important role. The role of polyunsaturated fatty acids (PUFAs) in AR is still controversial. Previous studies have looked at the effects of PUFA during pregnancy, childhood, and adolescence. In this study, we aimed to determine the association between dietary intake of PUFA and AR in adults. Methods: We used the NHANES database from 2005 to 2006 to include a total of 4,211 adult subjects. We collected dietary PUFA intake data and information on AR. Logistic regression and restricted cubic spline models were constructed to examine the association between PUFA intake and AR in adults. The t test was used to compare daily PUFA intakes in patients with and without AR. Results: In the fully adjusted model (OR: 1.016; 95% CI: 1.003; 1.028), PUFA intake was positively correlated with allergic symptoms, hay fever, and AR in adults (p < 0.05). In addition, daily PUFA intake was significantly higher in people with allergic symptoms, hay fever, and AR than in people without the disease (p < 0.01). Conclusions: Our results suggest a positive association between dietary PUFA intake and AR in adults to a certain extent. Future studies on dietary PUFA dose will provide new strategies for the prevention and treatment of allergic diseases such as AR related to non-pharmaceutical interventions.

Objectives: Head and neck squamous cell carcinoma (HNSCC) ranks sixth globally, with a 50% five-year survival rate. SAR1A exhibits high expression levels in various tumor types, yet its specific role in HNSCC remains to be clarified. Methods: In vitro assays, such as CCK8, EdU, colony formation, wound-healing, transwell, and Western blotting analyses, as well as in vivo assays, such as tumor xenografts and lung metastasis models, were conducted to evaluate the impacts of SAR1A on HNSCC proliferation, migration, and invasion. Transcriptome sequencing and KEGG enrichment pathway analysis revealed evident alterations in the PI3K/AKT/mTOR(PAM) pathways. LY294002 (a PI3K/AKT inhibitor) was used to investigate the role of the PAM pathway in proliferation, migration, and invasion in HNSCC. Results: Univariate and multivariate Cox regression were conducted to screen SAR1A as a gene prognostic biomarker in HNSCC, and it was validated in the Cancer Genome Atlas (TCGA) database. Functional assays demonstrated that the depletion of SAR1A leads to suppressed proliferation, migration, and invasion of HNSCC cells. This is accompanied by a decrease in the expression of epithelial–mesenchymal transition (EMT)-related markers in HNSCC cell lines. In addition, the diminished capacities of proliferation, migration, and invasion observed in SAR1A knockdown cells were reversed upon the overexpression of SAR1A. Furthermore, RNA-seq and KEGG enrichment analysis demonstrated a significant alteration in the PAM pathway following SAR1A knockdown. LY294002 effectively mitigated the increased proliferation, migration, and invasion induced by SAR1A overexpression. Conclusions: SAR1A facilitates HNSCC proliferation and EMT via the PI3K/AKT/mTOR pathway.

Studies have highlighted oxidative damage in the inner ear as a critical pathological basis for sensorineural hearing loss, especially the presbycusis. Poly(ADP-ribose) polymerase-1 (PARP1) activation responds to oxidative stress-induced DNA damage with pro-repair and pro-death effects resembling two sides of the same coin. PARP1-related cell death, known as parthanatos, whose underlying mechanisms are attractive research hotspots but remain to be clarified. In this study, we observed that aged rats showed stria vascularis degeneration and oxidative damage, and PARP1-dependent cell death was prominent in age-related cochlear disorganization and dysfunction. Based on oxidative stress model of primary cultured stria marginal cells (MCs), we revealed that upregulated PARP1 and PAR (Poly(ADP-ribose)) polymers are responsible for MCs oxidative death with high mitochondrial permeability transition pore (mPTP) opening and mitochondrial membrane potential (MMP) collapse, while inhibition of PARP1 ameliorated the adverse outcomes. Importantly, the PARylation of apoptosis-inducing factor (AIF) is essential for its conformational change and translocation, which subsequently causes DNA break and cell death. Concretely, the interaction of PAR and truncated AIF (tAIF) is the mainstream in the parthanatos pathway. We also found that the effects of AIF cleavage and release were achieved through calpain activity and mPTP opening, both of which could be regulated by PARP1 via mediation of mitochondria Ca2+ concentration. In conclusion, the PAR-Ca2+-tAIF signaling pathway in parthanatos contributes to the oxidative stress damage observed in MCs. Targeting PAR-Ca2+-tAIF might be a potential therapeutic strategy for the early intervention of presbycusis and other oxidative stress-associated sensorineural deafness.

Chemotherapeutic resistance is one of the most common reasons for poor prognosis of patients with nasopharyngeal carcinoma (NPC). We found that CENPN can promote the growth, proliferation and apoptosis resistance of NPC cells, but its relationship with chemotherapeutic resistance in NPC is unclear. Here we verified that the CENPN expression level in NPC patients was positively correlated with the degree of paclitaxel (PTX) resistance and a poor prognosis through analysis of clinical cases. VAMP8 expression was significantly increased after knockdown of CENPN by transcriptome sequencing. We found in cell experiments that CENPN inhibited macroautophagy/autophagy and VAMP8 expression and significantly increased PTX resistance. Overexpression of CENPN reduced the inhibitory effects of PTX on survival, cell proliferation, cell cycle progression and apoptosis resistance in NPC cells by inhibiting autophagy. In turn, knockdown of CENPN can affect the phenotype of NPC cells by increasing autophagy to achieve PTX sensitization. Sequential knockdown of CENPN and VAMP8 reversed the PTX-sensitizing effect of CENPN knockdown alone. Experiments in nude mice confirmed that knockdown of CENPN can increase VAMP8 expression, enhance autophagy and increase the sensitivity of NPC cells to PTX. Mechanistic studies showed that CENPN inhibited the translocation of p-CREB into the nucleus of NPC cells, resulting in the decreased binding of p-CREB to the VAMP8 promoter, thereby inhibiting the transcription of VAMP8. These results demonstrate that CENPN may be a marker for predicting chemotherapeutic efficacy and a potential target for inducing chemosensitization to agents such as PTX.Abbreviations: 3-MA: 3-methyladenine; ATG5: autophagy related 5; CENPN: centromere protein N; CQ: chloroquine; CREB: cAMP responsive element binding protein; ChIP: chromatin immunoprecipitation assay; IC50: half-maximal inhibitory concentration; LAMP2A: lysosomal associated membrane protein 2A; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; NPC: nasopharyngeal carcinoma; NPG: nasopharyngitis; oeCENPN: overexpressed CENPN; PTX: paclitaxel; RAPA: rapamycin; RNA-seq: transcriptome sequencing; shCENPN: small hairpin RNA expression vector targeting the human CENPN gene; shCENPN-shVAMP8: sequential knockdown targeting the human CENPN gene and VAMP8 gene; shVAMP8: small hairpin RNA expression vector targeting the human VAMP8 gene; TEM: transmission electron microscopy; TIR: tumor inhibitory rate; VAMP8: vesicle associated membrane protein 8.

Ubiquitin-specific protease 5 (USP5), a member of the ubiquitin-specific proteases (USPs) family, functions by specifically removing ubiquitin chains from target proteins for stabilization and degrading unbound polyubiquitin chains to maintain a steady-state monoubiquitin pool. Ubiquitin-specific protease 5 regulates various cellular activities, including DNA double-strand break repair, transmission of neuropathic and inflammatory pain signals, immune response, and tumor cell proliferation. Furthermore, USP5 is involved in the development of multiple tumors such as liver, lung, pancreatic, and breast cancers as well as melanoma. Downstream regulatory mechanisms associated with USP5 are complex and diverse. Ubiquitin-specific protease 5 has been revealed as an emerging target for tumor treatment. This study has introduced some molecules upstream to control the expression of USP5 at the levels of transcription, translation, and post-translation. Furthermore, the study incorporated inhibitors known to be associated with USP5, including partially selective deubiquitinase (DUB) inhibitors such as WP1130, EOAI3402143, vialinin A, and chalcone derivatives. It also included the ubiquitin-activating enzyme E1 inhibitor, PYR-41. These small molecule inhibitors impact the occurrence and development of various tumors. Therefore, this article comprehensively reviews the pivotal role of USP5 in different signaling pathways during tumor progression and resumes the progress made in developing USP5 inhibitors, providing a theoretical foundation for their clinical translation.

Background. Long noncoding RNAs (lncRNAs) often facilitate cellular communication via exosomes. However, their specific roles in head and neck squamous cell carcinoma (HNSCC) are not well understood. Methods. We extracted data on exosome-related lncRNAs from exoRBase and collected transcriptional profiles and clinical details for HNSCC from the TCGA database. Data preprocessing and analyses incorporated Tumor Mutation Burden and Microsatellite Instability from Researcher’s Home and drug sensitivity information from Genomics of Drug Sensitivity in Cancer database. We developed a prognostic model using Cox regression and LASSO regression analysis, with subsequent multivariate analysis to identify significant prognostic indicators. We also constructed a nomogram to evaluate the model’s clinical relevance, performed Gene Set Enrichment Analysis (GSEA), and analyzed the immune microenvironment and therapy sensitivity using CIBERSORT and TIDE algorithms. Supporting in vitro experiments and statistical analyses were conducted. Results. Our comprehensive investigation revealed 17 exosome-associated lncRNAs critical for patient survival in HNSCC. This enabled the development of a prognostic model that effectively stratifies patients into high-risk and low-risk categories. These lncRNAs correlate with patient demographics and clinical characteristics such as age, gender, and tumor stage. GSEA highlighted significant gene expression differences between the risk groups, particularly in pathways related to muscle formation, cellular transition, and immune response. The analysis of the immune microenvironment showed distinct immune cell infiltration patterns in high-risk patients, indicative of compromised immune defenses. In addition, we explored the expression of critical immune checkpoints and their impact on immunotherapy efficacy, demonstrating that risk scores may predict treatment responses. Notably, LINC01564 was overexpressed in HNSCC, associated with poorer prognosis, enhanced xenobiotic metabolism, and altered immune cell infiltration. Experimental validation confirmed LINC01564’s role in promoting tumor cell proliferation, invasion, and migration, highlighting its therapeutic potential. Conclusions. Our study highlights the importance of exosome-associated lncRNAs in HNSCC, identifying 17 critical lncRNAs as vital prognostic markers. The upregulation of LINC01564, associated with poor outcomes and increased tumor aggressiveness, underscores its potential as a therapeutic target.

Objective:To introduce the surgical experience of carotid body tumor（CBT） resection with preservation of internal carotid artery. Methods:The clinical data of 109 patients with CBT were retrospectively analyzed. The key points of surgical techniques were summarized, the imaging and pathological results were comprehensively analyzed, and the postoperative complications were observed. Results:Of the 109 patients, 28 were Shamblin Ⅰ, 46 were Shamblin Ⅱ, and 35 were Shamblin Ⅲ. Synaptophysin（SYN） and soluble protein-100（S-100） were positive in all cases. There was a positive correlation between the average expression area percentage of S-100 and SYN in pathological tissue of 17 patients（r=0.48）, and the difference was statistically significant（P<0.05）. The average operation time was（148.4±46.2） minutes, the average intraoperative blood loss was（64.7±22.8） mL, and the average hospital stay was（15.2±2.6） days. Three patients underwent tumor resection combined with external carotid artery ligation, 1 patient underwent tumor resection combined with internal carotid artery ligation, and the remaining patients underwent tumor resection alone. The overall rate of intraoperative vascular ligation was 3.7% and the rate of nerve injury was 6.4%. According to preoperative CTA, intraoperative situation and postoperative pathological results, a new classification of CBT was proposed, which could intuitively reflect the gap between the tumor and the carotid artery and the nature of the tumor. Conclusion:Surgical resection of CBT is recommended after diagnosis. The potential gap between the tumor and the blood vessels was found under the microscope. Low energy bipolar electrocoagulation was used to coagulate and cut off the fibrous connective tissue between the tumor and gradually separated along the adventitia of the artery. The carotid artery could be preserved in most cases while the tumor was completely removed, and the amount of intraoperative bleeding and the incidence of complications were reduced. It is particularly important to identify the difficult cases before operation.