Background: Head and neck squamous cell carcinoma (HNSCC) is a common malignancy with high morbidity and mortality. Despite advances in immunotherapy, including the advent of immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1), only a subset of patients achieves significant benefit. This study aimed to evaluate the prognostic significance of Dickkopf-related protein 1 (DKK1), a potential modulator of the tumor immune microenvironment (TME), and to assess the therapeutic impact of combining DKK1 inhibition with ICIs. Methods: Data from The Cancer Genome Atlas (TCGA) and a clinical cohort of 62 patients with HNSCC from Shanghai General Hospital were used to analyze DKK1 expression and its association with prognosis and immune cell infiltration. Tumor immune organoids were constructed by co-culturing tumor and immune cells from patient samples to mimic the TME and evaluate the effects of anti-DKK1 therapy. A preclinical mouse model using the MOC2 (mouse oral carcinoma 2) cell line was also used to test the therapeutic efficacy of combined anti-DKK1 and anti-PD1 treatment. Immune cell composition was analyzed using immunohistochemistry, immunofluorescence, and flow cytometry. Results: High DKK1 expression was found to correlate with poor patient prognosis and an immunosuppressive TME, characterized by reduced CD8+ T cell infiltration and increased myeloid-derived suppressor cells (MDSCs). In tumor immune organoids, anti-DKK1 treatment reduced organoid growth. In vivo, combined anti-DKK1 and anti-PD1 treatment led to significantly greater tumor growth inhibition compared to monotherapies, increased CD8+ T cell activity, and decreased MDSC levels, thereby creating an immune-stimulatory environment. Conclusions: DKK1 drives immune suppression in HNSCC and represents a promising therapeutic target. Tumor immune organoids offer a robust platform for studying tumor-immune interactions and evaluating combination immunotherapies. Combining anti-DKK1 and anti-PD1 treatment approaches has the potential to enhance antitumor immunity and improve outcomes in patients with HNSCC.

Rationale: Obstructive sleep apnea (OSA) is associated with cognitive impairment. The effects of continuous positive airway pressure (CPAP) on neuroimaging biomarkers and cognitive performance among middle-aged patients with OSA and normal cognition remain unclear. Objectives: To investigate the effects of CPAP therapy over 12 months on neuroimaging biomarkers and cognitive performance. Methods: In this multicenter, randomized clinical trial, we randomly assigned 148 participants with normal cognition and an apnea-hypopnea index ⩾15/h into two groups: patients receiving CPAP with best supportive care (BSC); and patients receiving BSC alone. The primary endpoint was Montreal Cognitive Assessment (MoCA) score at 6 months after enrollment. The secondary endpoints were intranetwork functional connectivity (FC) of default mode network (DMN) and cortical thickness assessed by functional and structural magnetic resonance imaging, other neuroimaging biomarkers, and neurobehavioral tests. Measurements and Main Results: Between 2017 and 2021, 148 patients were recruited from five hospitals. Linear mixed models showed that there was no significant difference in MoCA scores at 6 months between the CPAP and BSC groups (difference, -0.04; 95% confidence interval [CI], -0.72 to 0.65; P = 0.91). However, there were significant differences in the FC of DMN (difference, -13.73; 95% CI, -23.40 to -4.06; P = 0.01) and cortical thickness (difference, -0.06 mm; 95% CI, -0.10 to -0.01 mm; P = 0.02) between CPAP and BSC groups at 6 months after treatment. No serious adverse events occurred. Conclusions: CPAP improved cortical thickness and FC of DMN, suggesting that patients with OSA may recover from brain atrophic processes after CPAP treatment. However, no improvement in MoCA was found. Clinical trial registered with www.clinicaltrials.gov (NCT02886156).

BACKGROUND:Hypopharyngeal squamous cell carcinoma (HPSCC) is a lethal malignancy with limited treatment options and poor survival rates. Recent studies have revealed that mutations in the histone acetyltransferases EP300 and CREBBP drive tumor progression by disrupting the chromatin structure and impairing antitumor immunity. However, no targeted therapies are currently available to treat these epigenetic defects. Natural compounds with epigenetic regulatory potential offer a promising therapeutic avenue but remain largely unexplored in HPSCC. METHODS:Whole-exome and transcriptomic sequencing (WES) were conducted on HPSCC tissues to identify driver mutations and downstream transcriptional alterations. Histone acetylation profiles were analyzed by mass spectrometry and confirmed by western blotting. The effects of EP300/CREBBP mutations on H3K27ac enrichment at the PPARγ promoter were validated by ChIP-qPCR. Candidate targets, including PPARγ and ANGPT4, were identified through bioinformatics screening and verified by qRT-PCR and immunoblotting. Stable HPSCC cell lines carrying EP300 or CREBBP mutations were established via lentiviral transduction. Cell proliferation, apoptosis, and invasion were examined using Cell Counting Kit-8, TUNEL staining, and Transwell assays. The transcriptional regulation of ANGPT4 by PPARγ was evaluated using a dual-luciferase reporter assay. CD4⁺ T-cell subsets were analyzed by spectral flow cytometry. A xenograft model was established with FaDu cells in nude mice, and daidzein was administered intraperitoneally. Tumor growth, Ki-67 immunohistochemistry, and ELISA-based cytokine detection were used to assess therapeutic efficacy. RESULTS:Mutations in EP300 and CREBBP caused a marked loss of H3K27 acetylation and suppression of PPARγ, which in turn activated the ANGPT4/Tie2 oncogenic pathway and reshaped the immune microenvironment toward a regulatory T-cell-dominant profile. Treatment with daidzein effectively restored histone acetylation and PPARγ expression, leading to the inhibition of ANGPT4/Tie2 signaling and reversal of tumor-promoting phenotypes. In cultured HPSCC cells, daidzein reduced proliferation and invasion while inducing pronounced apoptotic changes. Dual-luciferase assays confirmed that PPARγ directly transactivated the ANGPT4 promoter, providing mechanistic evidence for its regulatory role. In animal models, intraperitoneal administration of daidzein (20-40 mg/kg) markedly delayed tumor growth, lowered Ki-67 expression, and reduced serum levels of immunosuppressive cytokines such as TGF-β and IL-35. Collectively, these findings indicate that daidzein acts as a dual activator of EP300 and PPARγ, re-establishing epigenetic balance and restoring antitumor immunity in EP300/CREBBP-deficient HPSCC. CONCLUSIONS:Through an integrated multi-omics strategy combining whole-exome sequencing, transcriptome profiling, and histone modification analysis in a Chinese HPSCC cohort, we identified recurrent loss-of-function mutations in EP300/CREBBP. These mutations reduced H3K27 acetylation and downregulated PPARγ, thereby activating the ANGPT4/Tie2 oncogenic signaling axis. Functional assays confirmed enhanced proliferation, invasion, and immune evasion, characterized by a regulatory T cell-dominant immune phenotype. Treatment with daidzein restored PPARγ expression, suppressed ANGPT4/Tie2 signaling, and reversed these malignant features, both in vitro and in vivo. Compared with previous studies, our work not only elucidates the functional consequences of EP300/CREBBP mutations in HPSCC but also proposes a novel therapeutic strategy targeting this axis. Importantly, we reveal a previously unrecognized EP300/CREBBP-PPARγ-ANGPT4/Tie2 axis and identify daidzein as a dual agonist of EP300 and PPARγ, providing mechanistic insights and translational potential for HPSCC therapy.

Thyroid cancer remains difficult to treat due to poor prognosis and drug resistance. Germacrone, a sesquiterpenoid from Curcuma longa, exhibits antitumor activity by modulating the PI3K/AKT-FOXO3 pathway. Here, we developed a responsive drug delivery system (1-CS-2-POSS@Germacrone) by modifying carboxymethyl chitosan (CMCS) with conjugated units (compound 1) and Jasminum sambac extract (compound 2), and stabilizing it with polyhedral oligomeric silsesquioxane (POSS). This design enhanced structural integrity, drug-loading efficiency, and electron conductivity for light-triggered release. FTIR and PXRD confirmed successful Germacrone loading via chemical and physical interactions. The bandgap narrowed from 2.43 eV to 2.26 eV, and the valence band shifted to 2.71 eV, indicating improved redox potential. EIS and photocurrent tests showed superior charge transport. Under 420 nm light, 9.1 μmol of Germacrone was released in 60 min with high reproducibility and an AQY of 4.12 %. Release was O2-dependent, decreasing sharply under N2. EPR and RRDE revealed a dominant 2e- ORR pathway with >90 % H2O2 selectivity, facilitating ROS-driven release. In vitro, the system inhibited BCPAP thyroid cancer cell proliferation and upregulated FOXO3, offering a promising strategy for precision therapy.

Background:Multifocal carcinoma is commonly reported in thyroid cancer. However, its impact on cancer survival is unclear. This study aims to evaluate whether multifocal disease is associated with better thyroid cancer outcomes in different ethnicities. Methods:Cancer registration data in the US from 2000 to 2016 were obtained via the Surveillance, Epidemiology, and End Results (SEER) 18 Registries database. Patients diagnosed with thyroid carcinoma and without other malignancies were enrolled. Univariable and multivariable Cox regressions were applied to evaluate the association of multifocal disease with cancer-specific survival (CSS) and overall survival (OS). Multivariable analyses were performed after adjusting for age, gender, stage, and treatment. Results:A total of 82,217, 8,551, 13,445, and 19,558 non-Hispanic White (NHW), non-Hispanic African American (AA), non-Hispanic Asian or Pacific Islander (AP), and Hispanic White (HW) patients were enrolled in this study, respectively. Univariable analysis suggested that multifocal carcinoma would have significant better CSS [hazard ratio (HR) =0.89, 95% confidence interval (CI): 0.77-1.02, P=0.09; adjusted HR =0.67, 95% CI: 0.53-0.85, P<0.001] and OS (HR =0.83, 95% CI: 0.77-0.90, P<0.001; adjusted HR =0.76, 95% CI: 0.65-0.87, P<0.001) than solitary disease in NHW. Conclusions:Multifocal thyroid carcinoma is associated with better CSS and OS than solitary cancer in NHW patients.

Abstract Background Cellular senescence refers to cells entering a relatively stable state of cell cycle arrest, which is a barrier that tumor cells must cross to achieve immortalization and plays an extremely important role in preventing the occurrence and development of tumors. In recent years, numerous studies have shown that inducing tumor cells to enter a senescent state has become a feasible tumor control strategy. At present, cellular senescence has become a research hotspot in tumor prevention and treatment, as well as in cell biology. However, the expression and prognostic values of cellular senescence genes in head and neck squamous cell carcinoma (HNSC) remain unclear. Material/Methods We analyzed the expression patterns and prognostic values of cellular senescence genes in HNSC from TCGA and GEO. The TCGA-HNSC data were used as the training group and were divided into high- and low-risk groups, and the GEO database was used as the test group. Analyses included survival analysis, ROC curve analysis, risk curve analysis, independent prognostic analysis and model validation for clinical grouping. We used the HPA database for protein-level validation of the genes. Results We identified 5 cellular senescence genes associated with HNSC, namely, BTG3, EHF, EZH2, TACC3 and TXN. These cellular senescence genes were analyzed in the training and test groups and were found to be significantly associated with the prognosis of HNSC patients. Conclusions The tumor immune microenvironment of HNSC appears to have correlations with certain cellular senescence-related features. Genes associated with cellular senescence, such as BTG3, EHF, EZH2, TACC3, and TXN, show promise as potential diagnostic and prognostic biomarkers for HNSC.

Head and neck cancer is the main cause of cancer death worldwide, with squamous cell carcinoma (HNSCC) being the second most frequent subtype. HNSCC poses significant health threats due to its high incidence and poor prognosis, underscoring the urgent need for advanced research. Histone modifications play a crucial role in the regulation of gene expression and influencing various biological processes. In the context of HNSCC, aberrant histone modifications are increasingly recognized as critical contributors to its development and pathologic progression. This review demonstrates the molecular mechanisms, by which histone modifications such as acetylation, methylation, phosphorylation, and ubiquitination, impact the pathogenesis of HNSCC. The dysregulation of histone-modifying enzymes, including histone acetyltransferases (HATs), histone deacetylases (HDACs), and histone methyltransferases (HMTs), is discussed for its role in altering chromatin structure and gene expression in HNSCC. Moreover, we will explore the potential of targeting histone modifications as a therapeutic strategy, highlighting current preclinical and clinical studies that investigate histone deacetylase inhibitors (HDIs) and other epigenetic drugs, referring to the completed and ongoing clinical trials on those medications.

The mucosal epithelium of the head and neck region (including the oral cavity, nasal cavity, pharynx, nasopharynx, and larynx) is the primary site exposed to tobacco smoke, and its presence of nicotinic acetylcholine receptors (nAChRs) has been observed in the mucosal epithelial cells of this area. It remains unclear whether HNSC cells can migrate and invade through nAChR signaling. A model of HNSC cells exposed to nicotine is established. Cell proliferation following nicotine exposure is assessed using the CCK-8 assay, while migration and invasion are evaluated through wound healing and Transwell assays. The effects of CHRNA5 knockdown and overexpression are also investigated. Immunofluorescence staining is used to analyze CHRNA5 expression and localization, and clonogenic assays are performed to measure colony proliferation after CHRNA5 knockdown and overexpression. The interaction between CHRNA5 and CES1 is examined using molecular docking, co-immunoprecipitation, and immunofluorescence. Differentially expressed genes are subjected to pathway enrichment analysis, and MEK/ERK protein expression and phosphorylation are validated via western blot. Tumor formation assays are performed in nude mice using sh-CHRNA5 Cal27 cells, followed by western blot and immunohistochemical staining. Additionally, laryngeal and hypopharyngeal cancer tissues are analyzed through immunohistochemistry. Nicotine significantly enhanced the proliferation, migration, and invasion capabilities of head and neck tumor cells, including Cal27, Fadu, HN6, and Tu686 cells, through the expression of CHRNA5. Knockdown of CHRNA5 can reduce cell migration, invasion, and proliferation, whereas nicotine exposure can reverse this trend. Additionally, the mRNA and protein expression of CES1 decreases with the knockdown of CHRNA5, indicating a regulatory relationship between the two. Transcriptomics revealed that the knockdown of CHRNA5 is associated with the MEK/ERK signaling pathway. Further cellular- and tissue-level evidence confirmed that the levels of p-MEK/MEK, p-ERK/ERK, and CES1 decreased following knockdown of CHRNA5, a trend that nicotine can reverse. Nicotine promotes the proliferation, migration, and invasion of HNSC by upregulating CHRNA5 expression. Knockdown of CHRNA5 reduces these effects, which can be reversed by nicotine. Nicotine exposure activates CHRNA5, regulating CES1 expression via the MEK/ERK pathway, contributing to the recurrence and metastasis of head and neck squamous carcinoma.

OBJECTIVE:Auricular pseudocysts are rare, painless, benign intracartilaginous cysts of the auricle that are not lined by epithelium and have no known aetiology.METHOD:This was a prospective study conducted in an ENT department from January 2020 to June 2022. In 21 patients, complete aspiration of the pseudocyst with enhanced negative drainage was performed. They were followed for a minimum of six months.RESULTS:All patients completely responded to the negative drainage treatment. No cases of recurrence or obvious deformities were observed.CONCLUSION:Aspiration with intensified negative drainage was associated with a positive response in patients with auricular pseudocysts. Complete resolution of the swelling can be achieved without any serious complications. Thus, it appears to be a simple and effective method for managing the condition.

Background: Allergic rhinitis (AR) is a multifactorial disease triggered by interactions between genes and the environment. Clinical evidence has shown that trans-resveratrol, a widely used drug, significantly ameliorates AR pathology. However, the precise mechanisms underlying this effect remain unclear. Purpose: This study aimed to elucidate the pharmacological mechanisms of action of trans-resveratrol in patients with AR who exhibit hypoxic symptoms. This will be achieved through microRNA sequencing and signaling pathway screening combined with basic experiments to determine the effects of Trans-resveratrol intervention in this patient population. Methods: Network pharmacology was used to determine the therapeutic value of trans-resveratrol in AR. The micro-RNA miR-204-3p was pinpointed by sequencing. Quantitative reverse transcription polymerase chain reaction was used to quantify the expression levels. Haematoxylin and eosin, alcian blue-periodic acid-Schiff, and Masson's trichrome staining were used to assess the effects of hypoxia on nasal mucosa immunohistochemistry and immunofluorescence-localised target proteins. Egl nine homolog 3 (EGLN3) was screened using bioinformatics software. Protein expression was detected by western blotting. Cell growth and death were gauged via Cell Counting Kit-8 and terminal deoxynucleotidyl transferase dUTP nick end labelling staining, respectively. Cell migration was observed using a transwell assay. Enzyme-linked immunosorbent assay was used to measure interleukin (IL)33 levels in the cell supernatants. Flow cytometry was used to verify cell cycle and antigen levels. Electron microscopy was used to visualise the status of the nasal mucosa prior to in vivo expression analysis. Results: Patients with hypoxic AR demonstrated more pronounced nasal mucosal remodelling than that in patients with common AR. Sequencing results indicated that these patients had a reduced expression of miR-2043p. Through a combination utilizing of bioinformatics analysis and experimental validation, EGLN3 has been identified as a direct target of HIF-1 alpha. The low expression level of miR-204-3p represses EGLN3, resulting in the accumulation of HIF-1 alpha and the activation of the IL33/ST2 signaling pathway. These stimulate the proliferation, survival, and migration of HNEpCs, ultimately contributing to mucosa remodeling and AR progression. Transresveratrol notably downregulated the levels of HIF-1 alpha and IL33/ST2, while simultaneously increasing the expression of EGLN3. Conclusions: Downregulation of miR-204-3p initiated a vicious cycle of hypoxic AR via EGLN3/HIF-1 alpha/IL33/ST2. Trans-resveratrol reversed the pathological process of nasal mucosa remodeling of hypoxic AR by exhibiting antiinflammatory and anti-angiogenic functions via the above signaling pathway. Our study uncovers the underlying mechanism by which hypoxia drives the progression of AR. It presents innovative strategies for addressing inflammatory and hypoxia-related diseases, bridging traditional and modern medicine, and highlighting the potential of natural compounds in clinical practice.

Immunotherapy combined with chemotherapy regimen has been shown to be effective in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, due to the small number of patients, its efficacy remains controversial in Asian populations, particularly in mainland China. Here a randomized, double-blind phase 3 trial evaluated the efficacy and safety of finotonlimab (SCT-I10A), a programmed cell death 1 (PD-1) monoclonal antibody, combined with cisplatin plus 5-fluorouracil (C5F) for the first-line treatment of R/M HNSCC. Eligible patients (n = 370) were randomly 2:1 assigned to receive finotonlimab plus C5F (n = 247) or placebo plus C5F (n = 123). The primary endpoint was overall survival (OS). In the finotonlimab plus C5F group, OS was 14.1 months (95% confidence interval (CI) 11.1-16.4), compared with 10.5 months (95% CI 8.1-11.8) in the placebo plus C5F group. The hazard ratio was 0.73 (95% CI 0.57-0.95, P = 0.0165), meeting the predefined superiority criteria for the primary endpoint. Finotonlimab plus C5F showed significant OS superiority compared with C5F alone and acceptable safety profile with R/M HNSCC, supporting its use as a first-line treatment option for R/M HNSCC. These results validate the efficacy and safety of the combination of finotonlimab and C5F in Asian patients with R/M HNSCC. ClinicalTrials.gov identifier: NCT04146402. In this phase 3 trial, first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma with anti-PD-1 finotonlimab plus cisplatin plus 5-fluorouracil (C5F) prolonged overall survival compared with placebo plus C5F.

Background: The microenvironment of head and neck squamous cell carcinoma (HNSC) is made up of cancer and non-cancerous cells, and their interactions have profound effects on anti-tumor immunity. However, a thorough understanding of the genetic and cellular-level intercellular communication networks involved in tumor progression remains a significant obstacle. Material/Methods: 460 HNSC patients from various cohorts were included. To identify the marker genes, we analyzed single-cell RNA-sequencing (scRNA-seq) data from GEO database. An analysis of immunological infiltrating cell density was carried out using cell-type identification by calculating relative subsets of RNA transcripts (CIBERSORT). The bulk RNA-seq dataset from TCGA database was used to construct signature, and the GSE 65858 were used for validation. And the expression of related proteins were verified using HPA database and western blotting. Results: A three-gene signature (CES1, ELF3 and SERPINE1) was developed for prognostic prediction in the TCGA dataset, which divided patients into high-risk and low-risk categories based on overall survival. The prognostic potential of the signature was confirmed by GSE 65858. The signature protein expression was validated by HPA database and western blotting. Furthermore, the riskScore was identified as a significant prognostic factor in the multivariate analysis, indicating that the signature had high predictive ability. In addition, patients with high-risk scores obtained fewer benefits from immunotherapy. Conclusions: Our study identified a distinctive predictive signature for HNSC patients based on CES1, ELF3, and SERPINE1. The signature may be used as a predictor for immunotherapy and as an indicator of survival in patients with HNSC.

Background: Obstructive sleep apnoea (OSA) is associated with cognitive decline. The potential benefits of continuous positive airway pressure (CPAP) on cognitive performance and brain structure and function in middle-aged OSA and normal cognition remain unclear.Methods: In this 12-month, multicentre randomized clinical trial, we randomly assigned 148 moderate to severe OSA and normal cognition into two groups: patients receiving CPAP with best supportive care (BSC) and patients receiving BSC alone. The primary endpoint was the MoCA score at 6 months after enrollment. The secondary endpoints were cognitive function assessed by MMSE, a neurobehavioral test, and brain structure and function assessments by T1 sMRI and resting-state BOLD fMRI. Both full analysis set and per-protocol analyses were performed. This study is registered with ClinicalTrials.gov, NCT02886156.Findings: Between 2017 and 2021, 148 patients were randomly assigned, of whom 126 (85.1%) completed this trial. Linear mixed models showed that there was no significant difference in MoCA scores between the two groups from baseline to 12 months (P = 0.365). However, T1 sMRI and resting-state BOLD fMRI showed statistically significant increases in the gray and white matter volumes, an increase in cortical complexity, and improvements in the amplitude of low-frequency fluctuation, regional homogeneity, and intranetwork functional connectivity analysis of the default mode network following CPAP treatment. No serious adverse events occurred during the trial.Interpretation: Compared to BSC alone, CPAP plus BSC improved brain structure and function in OSA, but no benefit was observed for cognition. Trial Registration: This study is registered with ClinicalTrials.gov, NCT02886156.Funding: This study was supported by STI2030-Major Projects (2021ZD0201900) from National Key R&D Program of China; a grant (DLY201502) from multi-center clinical research project from school of medicine, Shanghai Jiao Tong University; a grant (18DZ2260200) from Shanghai Municipal Commission of Science and Technology; grants (SHDC2020CR2044B; SHDC2020CR3056B) from three-Year Action Plan of Promoting Clinical Skills and Clinical Innovation in Shanghai Shen Kang Medical Center; a grant (2017-01-07-00-02-E00047) from Innovation Program of Shanghai Municipal Education Commission. Declaration of Interest: No conflict of interest disclosures were reported.Ethical Approval: The human ethics committee of each hospital approved the study protocol, and all patients gave written informed consent.

Objective:To analyze the risk factors that affect the prognosis of patients with hypopharyngeal squamous cell carcinoma（HPSCC） and to compare the efficacy of surgical resection followed by adjuvant radiotherapy（SR） with that of neoadjuvant therapy consisting of platinum-based chemotherapy and fluorouracil combined with either cetuximab or nimotuzumab, followed by SR. The study also aimed to evaluate the overall survival（OS） of patients, their postoperative eating function, tracheostomy decannulation rate, and tumor response to the two neoadjuvant chemotherapies. Methods:A retrospective analysis was performed on the medical records of HPSCC patients who received SR or neoadjuvant therapy followed by SR treatment at the Shanghai General Hospital from 2012 to 2019 and had not undergone any prior treatment. The prognostic factors were analyzed, and the survival analysis of patients who underwent SR treatment with two neoadjuvant chemotherapy regimens was performed. Results:A total of 108 patients were included in the study. The results of the univariate analysis showed that gender（P=0.850） had no significant correlation with the survival rate of HPSCC patients who underwent SR. However, age, smoking history, alcohol consumption history, platelet-to-lymphocyte ratio（PLR）, neutrophil-to-lymphocyte ratio（NLR）, T stage, N stage, neoadjuvant therapy with either cetuximab or nimotuzumab combined with platinum-based chemotherapy and fluorouracil, and histological grade were significantly associated with prognosis（P<0.05）. The multivariate analysis revealed that smoking history, histological grade, and neoadjuvant therapy with either cetuximab or nimotuzumab combined with platinum-based chemotherapy and fluorouracil were independent risk factors affecting the prognosis of HPSCC（P<0.05）. Patients who received neoadjuvant therapy had longer OS than those who underwent SR only（P<0.001）. There was no significant difference in tumor response to the two neoadjuvant therapies and in OS（P>0.05）, and there was no significant difference in the rate of oral feeding and tracheostomy decannulation among the three treatment groups（P>0.05）. Conclusion:Univariate analysis showed that age at tumor onset, smoking history, alcohol consumption history, NLR, PLR, T stage, N stage, whether receiving neoadjuvant chemotherapy, and pathological grade were associated with the prognosis of HPSCC patients receiving SR treatment. Multivariate analysis showed that smoking history, pathological grade, and neoadjuvant chemotherapy were independent risk factors affecting the prognosis. Neoadjuvant chemotherapy with cetuximab or nimotuzumab can prolong the OS of patients, providing a certain basis and reference for the treatment of HPSCC.

The oncological and functional role of postoperative radiotherapy (PORT) after open partial laryngeal surgery (OPLS) remains debatable. A systematic review and a meta-analysis of the literature were conducted according to the PRISMA guidelines. Outcomes of patients receiving OPLS with and without PORT for laryngeal cancer were summarized. In the 10 studies that were included in the meta-analysis, no significant difference emerged in terms of pooled overall survival between OPLS patients who did and who did not receive PORT (− 0.3

Background: There is a research gap between genetic predisposition, socioeconomic factors, and their interactions on thyroid tumorigenesis. Methods: Individual and genetic data were obtained from UK Biobank. Logistic regression models were used to evaluate the association between genetic risk, socioeconomic factors, and thyroid cancer (TCa). A stratified analysis was conducted to estimate their joint effects. A two-sample Mendelian randomization (MR) analysis was further used to examine the potential causality. Results: A total of 502,394 participants were included in this study. Three index loci (rs4449583, rs7726159, and rs7725218) of telomerase reverse transcriptase (TERT) were found to be significantly related to incident TCa. Association analyses showed that high genetic risk, low household income, and high education level were independent risk factors, while unemployment and frequent social connection were suggestive risk factors for TCa. Interaction analyses showed that in participants with low genetic risk, low household income was significantly associated with TCa (odds ratio [OR] = 1.56, 95% confidence interval [CI]: 1.00–2.46). In participants with high genetic risk, those with a high education level (OR = 1.32, 95%CI: 1.06–1.65) and frequent social connection (OR = 1.36, 95%CI: 1.02–1.81) had a significantly increased risk of TCa. However, no causal relationship was observed in the MR analysis. Conclusion: Interactions exist between genetic risk, household income, education level, and social connection and thyroid cancer.

N4-acetylcytidine (ac4C) is a post-transcriptional RNA modification that regulates in various important biological processes. However, its role in human cancer, especially lymph node metastasis, remains largely unknown. Here, we demonstrated N-Acetyltransferase 10 (NAT10), as the only known “writer” of ac4C mRNA modification, was highly expressed in head and neck squamous cell carcinoma (HNSCC) patients with lymph node metastasis. High NAT10 levels in the lymph nodes of patients with HNSCC patients are a predictor of poor overall survival. Moreover, we found that high expression of NAT10 was positively upregulated by Nuclear Respiratory Factor 1 (NRF1) transcription factor. Gain- and loss-of-function experiments displayed that NAT10 promoted cell metastasis in mice. Mechanistically, NAT10 induced ac4C modification of Glycosylated Lysosomal Membrane Protein (GLMP) and stabilized its mRNA, which triggered the activation of the MAPK/ERK signaling pathway. Finally, the NAT10-specific inhibitor, remodelin, could inhibit HNSCC tumorigenesis in a 4-Nitroquinoline 1-oxide (4NQO)-induced murine tumor model and remodel the tumor microenvironment, including angiogenesis, CD8+ T cells and Treg recruitment. These results demonstrate that NAT10 promotes lymph node metastasis in HNSCC via ac4C-dependent stabilization of the GLMP transcript, providing a potential epitranscriptomic-targeted therapeutic strategy for HNSCC.

急性声损伤,又称爆震性聋,是由短暂而强烈的爆炸所引起的听力损伤,可以导致显性/隐性听力损失,常伴发耳鸣和/或听觉过敏等听觉感知障碍,进而引发焦虑,严重影响患者生活质量.听觉感知障碍发病机制复杂,可能与听力损伤、炎症、遗传等多方面因素有关.临床上常以掩蔽法或噪声脱敏法治疗,但患者很少痊愈.现就急性声损伤致耳鸣、听觉过敏的发病机制做简要综述,以期为临床治疗提供思路.

Human CUB and Sushi multiple domains (CSMD1) is considered a crucial role in cancer progression, but the specific function in esophageal squamous cell carcinoma (ESCC) is not clear. Understanding the role of CSMD1 in ESCC progression may lead to a novel strategy for ESCC treatment. Here, we found that both CSMD1 mRNA and protein levels were downregulated in ESCC tissues. Reduced CSMD1 expression was correlated with a poor prognosis in ESCC patients. CSMD1 expression inhibited proliferation, migration and invasion in ESCC cell lines in vitro. CSMD1 deficiency in established xenografted tumors increases tumor size and weight. We further found that CSMD1-overexpression cells are more sensitive to chemotherapy. Moreover, we addressed the role of CSMD1 in the CD8+ T cell immune response. An in vitro killing assay showed that the cytotoxicity of CD8+ T cells was inhibited in CSMD1-overexpression tumor cells. In vivo, in CSMD1 deficiency tumor-bearing mice activation and expansion of CD8+ T cells were increased. Further investigation showed that CSMD1 expression on tumor cells was positively correlated with CD8+ T cells infiltration and cytokines secretion. These findings highlight that CSMD1 is a tumor suppressor gene in ESCC patients and a positive regulator of CD8+ T cells expansion and activation, and could increase cytokines secretion, indicating that tumor cell-associated CSMD1 might be a target for ESCC.

Objective:To test the feasibility of a rigid curved video laryngoscope in laryngeal microsurgery of patients with difficult laryngeal exposure. Methods:Thirteen patients with difficult laryngeal exposure underwent microlayngeal surgery using a new-design rigid curved video laryngoscope. The clinical data were collected and analyzed. Results:In all of the 13 patients with difficult laryngeal exposure,the fully exposure rate of glottis was 100% using a new-design rigid curved laryngoscope.But only 7 precise surgeries using our rigid curved instruments were completed successfully. Conclusion:Rigid curved laryngoscope is a useful tool to in treating patients with difficult laryngeal exposure in microlaryngeal surgery. Satisfactory glottis exposure, magnified surgical field and precise maneuver of the lesions could be achieved. But manipulation of this tool is challenging, which warrants further investigation．.