BACKGROUND: Sudden sensorineural hearing loss (SSNHL) is an otological emergency with incompletely understood pathophysiology. Evidence suggests microcirculatory dysfunction and oxidative stress contribute to cochlear injury; however, their interrelationship remains insufficiently characterized. MATERIAL AND METHODS: This prospective case-control study enrolled 100 patients with SSNHL and 100 age- and sex-matched healthy controls. Perfusion-related surrogate parameters, including cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT), were assessed using dynamic contrast-enhanced magnetic resonance perfusion imaging. Peripheral microcirculation was evaluated by laser Doppler flowmetry. Systemic oxidative stress markers malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were quantified in serum. Experimental validation was performed using a rat ischemia-reperfusion model to assess cochlear oxidative stress, apoptosis, and auditory brainstem response thresholds. RESULTS: Compared with controls, SSNHL patients exhibited reduced CBF and CBV, prolonged MTT, and lower peripheral microcirculatory perfusion (all P<0.05). Oxidative stress was increased in SSNHL, reflected by elevated serum MDA levels and reduced SOD and GSH-Px activities. Animal model showed ischemia-reperfusion induced parallel alterations, including increased cochlear oxidative stress, reduced antioxidant enzyme activity, increased apoptotic cell burden, and elevated auditory brainstem response thresholds. Perfusion-related parameters correlated with oxidative stress markers. Multivariable regression analysis demonstrated independent associations between perfusion profiles, oxidative imbalance, and hearing thresholds. CONCLUSIONS: SSNHL is associated with unfavorable perfusion-related surrogate parameters and heightened oxidative stress accompanied by reduced antioxidant defenses. Clinical and experimental findings suggest microcirculatory dysfunction and oxidative imbalance are interrelated features of SSNHL-associated cochlear injury. Causal inference cannot be established, and further mechanistic studies are warranted.

OBJECTIVE:The objective of this study is to search for hydroxysafflor yellow A (HSYA) and Idiopathic sudden sensorineural hearing loss (ISSNHL)-related target genes and to study the treatment effects of HSYA on lipopolysaccharide (LPS)-induced endothelial cell injury. METHODS:We used network pharmacology to screen molecules related to HSYA and ISSNHL, then analyzed these molecules and their enriched biological processes and signaling pathways via Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). We selected inflammation-related hub genes for molecular docking determination by protein-protein interaction (PPI) analysis, and further verified them with in vitro experiments. RESULTS:Thirty-four HSYA-ISSNHL-related differential genes were obtained using drug-disease differential gene screening using online tools. Three key proteins, NF-κB, CASP3, and MAPK1, were selected according to Degree > 20. Among them, NF-κB is closely related to inflammation and ISSNHL. In in vitro experiments, HSYA reduced inflammatory (IL-6, TNF- α) and oxidative stress (ROS, SOD and MDA) indicators after LPS intervention, and the expression of NF-κB-related signaling pathway genes. CONCLUSION:HSYA may reduce inflammation and oxidative stress by inhibiting the expression of the TLR4 / NF-κB-related signaling pathway, therefore protecting endothelial cells, which might be a potential mechanism of HSYA in ISSNHL treatment.

Objective:To assess the clinical effectiveness of postauricular injection of methylprednisolone in the treatment of individuals with sudden deafness (SD) and to identify influencing factors. Methodology:In this retrospective study, we included clinical data of 106 eligible patients with SD who were hospitalized in the Department of Otorhinolaryngology of Nanjing Integrated Traditional Chinese and Western Medicine Hospital from October 2023 to October 2024. According to the different routes of administration of methylprednisolone, patients were divided into an observation (OBP) (n=54) and a control (CGP) (n=52) group. The CGP group received routine treatment of intravenous methylprednisolone combined with conventional medication and the OBP group received retroauricular injection of methylprednisolone in addition to the routine treatment. Results:Patients in the OBP group reported a considerably better overall efficacy (87.0% vs. 67.3%) and tinnitus (74.1% vs. 60.7%) than the CGP group. The vertigo disappearance time (5.19±1.29 d vs 5.35±1.06 d) and ear fullness sensation halo disappearance time (5.73±1.21 d vs 6.16±1.27 d) in the OBP group were considerably shorter than in the CGP group (P<0.05). Levels of Homocysteine (HCY), High Shear Blood Viscosity (HBV), Low Shear Blood Viscosity (LBV), Plasma Viscosity (PV) and Hematocrit (HCT) in both groups decreased significantly after therapy and were substantially lower in the OBP group compared to the CGP group (p < 0.05). Conclusion:Compared to conventional treatment, postauricular injection of methylprednisolone can enhance the treatment efficacy of SD and is associated with improvement in accompanying symptoms. Postauricular injection of methylprednisolone can more effectively reduce HCY, HBV, LBV, PV and HCT levels in SD patients.

Glucocorticoids (GCs) are commonly used to treat sudden sensorineural hearing loss (SSNHL), although some patients are resistant to this therapeutic approach. Clinical studies have demonstrated the efficacy oftanshinone IIA (TA) in combination with GC for managing various human ailments. However, it remains unclear whether TA can mitigate GC resistance in SSNHL. Our aim is to elucidate the role of NRF2-induced transcriptional regulation of HDAC2 in influencing GC resistance and investigate the involvement of TA-related molecular pathways in GC resistance. Here, HEI-OC1 cells are treated with lipopolysaccharide (LPS) to establish an in vitro model for SSNHL. The cells are subsequently treated with dexamethasone (DXE) or DXE + TA. RT-qPCR and western blot analysis are used to measure the mRNA and protein levels of Forkhead box P3 (FOXP3), nuclear factor erythroid 2-related factor 2 (NRF2), and histone deacetylase 2 (HDAC2). Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays are carried out to assess cell proliferation. Flow cytometry analysis is performed to evaluate apoptosis. Mechanistic studies involve chromatin immunoprecipitation (ChIP), luciferase reporter, and DNA pull-down assays. Our results show that treatment with TA + DEX significantly increases proliferation and suppresses apoptosis in LPS-treated HEI-treated OC1 cells. TA upregulates HDAC2 expression by activating NRF2-mediated transcription of HDAC2, with the NRF2-HDAC2 binding site located at bases 419-429 (ATGACACTCCA) in the promoter sequence of HDAC2. Furthermore, TA upregulates FOXP3 expression to activate NRF2 transcription, with the predicted FOXP3-binding site located at bases 864-870 (GCAAACA) in the promoter sequence of NRF2. In summary, these findings suggest that TA enhances the therapeutic effects of GC on the proliferation and apoptosis of HEI OC1 cells by increasing FOXP3/Nrf2 expression. These results indicate that TA may be promising for ameliorating GC resistance in patients with SSNHL.

Objective:This study aimed to evaluate the therapeutic effect of intratympanic injection of ganglioside in patients with refractory sudden deafness. Methods:A total of 120 patients with sudden deafness, aged 18-65 years, whose onset was within 11-42 days, failed to respond to conventional treatment, and had an average hearing threshold（500-4 000 Hz）>60 dB were selected. They were prospectively and randomly divided into a control group of 61 cases and an experimental group of 59 cases. The control group was treated according to the recommended protocol of the Chinese Medical Association（postauricular injection of methylprednisolone）, while the experimental group was treated with intratympanic injection of monosialotetrahexosylganglioside sodium+postauricular injection of methylprednisolone. Both groups were simultaneously administered oral ginkgo biloba extract and citicoline tablets. Hearing was re-examined two weeks after the completion of treatment, and the therapeutic effects of the two different treatment methods were compared and analyzed. Results:The effective rate was 29.51% in the control group and 54.24% in the experimental group（P<0.01）. The average hearing threshold improved by 11.57 dB HL in the control group and 22.50 dB HL in the experimental group（P<0.05）. Conclusion:The combination of postauricular injection of methylprednisolone and intratympanic injection of ganglioside is more effective than postauricular injection of methylprednisolone alone in the treatment of refractory sudden deafness. The earlier the treatment, the better the therapeutic effect.

Objectives:To investigate the expression of hypoxia-inducible factor-1α (HIF-1α) in patients with refractory sudden sensorineural hearing loss (SSNHL). Material and methods:Thirty patients with refractory SSNHL were treated with intratympanic methylprednisolone perfusion (IMP) for 10 days. Expression of HIF-1α and histone deacetylase 2 (HDAC2) was evaluated in peripheral blood mononuclear cells (PBMCs) and in vitro. Results:Significant hearing improvement (≥ 15 dB) was observed in 16 patients [IMP glucocorticoid sensitive (GCS) group], while 14 patients had no therapeautic hearing recovery [IMP GC resistance (GCR) group]. The expression of HDAC2 decreased and HIF-1a increased in all refractory SSNHL patients before IMP. The expression of HDAC2 and HIF-1α after IMP was significantly changed in the GCS group, but not in the GCR group. The same expression profile was also observed in House Ear Institute-organ of Corti-1 (HEI-OC1) cells exposed to oxidative stress (OS). The results of gene manipulation experiments indicate that HIF-1α up-regulation significantly reduced HDAC2 expression in HEI-OC1 cells, especially under conditions of OS. Conclusions:This study suggests that HIF-1α activation inhibits HDAC2 expression, causing glucocorticoid resistance in refractory SSNHL. HIF-1α might serve as a potential biomarker to predict prognosis of refractory SSNHL.

Glucocorticoids（GC） are widely used in the clinical treatment of autoimmune inner ear diseases, sudden sensorineural hearing loss, Meniere's disease, sinusitis and other otolaryngology diseases. However, GC resistance remains a major factor contributing to the poor efficacy of clinical treatments. The mechanism of GC resistance is still unclear. This paper reviews the related mechanisms of GC resistance from the perspectives of GC receptor factors and non-GC receptor factors. Additionally, it summarizes the latest research progress on GC resistance in otolaryngological diseases, with the aim of identifying effective clinical alternative treatment options for reversing GC resistance in the future.

目的 探讨甲磺酸倍他司汀对良性阵发性位置性眩晕(BPPV)位置试验眼震的影响.方法 2022年1～6月就诊的头晕患者并且予BPPV位置试验检查,其中61例检查前24 h内仅口服过甲磺酸倍他司汀治疗,199例检查前24 h内口服其他药物或者多种药物联合治疗.观察其停药前、后BPPV位置试验眼震变化情况:检查前24 h内有用药史者,先予第1次BPPV位置试验,记录眼震情况;若第1次位置试验为阴性,嘱其停药24 h后再予第2次BPPV位置试验,记录眼震情况;若第1次位置试验为阳性,予手法复位治疗,1 h后复查,若复位效果欠佳,嘱其停药24 h后再予第2次BPPV位置试验,记录眼震情况.位置试验眼震均通过视频眼罩观察.结果 检查前24 h内仅口服过甲磺酸倍他司汀的患者中,第1次BPPV位置试验眼震阳性者占16.39%(10/61),停药24 h后第2次BPPV位置试验眼震阳性者占49.02%(25/51),停药前、后BPPV位置试验眼震阳性率有显著统计学差异(χ2=8.89,P=0.003).第1次位置试验眼震阳性者中,有5例(50%)在停药24 h后第2次位置试验中眼震强弱程度发生变化,导致定位患侧半规管发生变化:2例左水平半规管BPPV修正为右水平半规管BPPV;1例左水平半规管嵴帽型BPPV修正为右水平半规管嵴帽型BPPV;2例水平半规管嵴帽型BPPV,从第1次位置试验无法根据眼震强弱程度辨别患侧,到第2次位置试验可以根据眼震强弱程度明确患侧.结论 甲磺酸倍他司汀对BPPV位置试验的精确性有一定影响,主要表现为抑制患者发病时原有的眼震,建议停药24 h后再做位置试验,有助于BPPV精准诊疗.

Objective:To establish a hearing care network for preschool children in Nanjing, to perform early identification and intervention for delayed hearing loss, and to evaluate the application effect of the hearing care network. Methods:Through the establishment of a hearing care network, hearing screening, diagnosis and follow-up of preschool children were conducted. Distortion product otoacoustic emissions（DPOAE） was adopted for primary hearing screening. Children who failed in the primary screening were re-screened within half a month. DPOAE and acoustic impedance test were used for hearing re-screening. Clinical diagnosis and audiological evaluation were performed for children who failed in the re-screening. Speech assessment, hearing aid intervention, and audio-speech follow-up were conducted for children diagnosed with delayed hearing loss. Results:Among 29 919 preschool children completing the hearing screening from May 2019 to September 2022, 3208 cases（10.7%） failed the primary screening and 1437 cases（47.7%） failed the re-screening. Total 747 children completed the hearing diagnosis, and 70 children were diagnosed with delayed hearing loss, with a detection rate of 0.23%. Among them, 20 cases were accompanied by language development delay, in which 12 cases received hearing aids and 2 cases received cochlear implantation. In addition, speech assessment and audiological follow-up were completed for 53 children. Conclusion:The hearing screening for preschool children is beneficial for early detection of children with delayed hearing loss and language development delay. Besides, the establishment of hearing care network is conducive to early identification and intervention of children with hearing loss.

Background: Despite its widespread therapeutic use and effectiveness, the underlying pharmacologic mechanisms of Wendan decoction (WDD) and how it works to treat sudden deafness (SD) remain unclear. In this study, the pharmacological mechanisms of WDD underlying SD were analyzed using network pharmacology and molecular docking.Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was employed to identify the active compounds and target genes of WDD, and genes associated with SD were screened on five databases. RGUI conducted Gene Ontology (GO) functional and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A compound-target network was established using Cytoscape, and the STRING database created a protein-protein interaction (PPI) network to identify the key compounds and targets. Subsequently, a network of crucial compound-target was generated for further molecular docking analysis. For molecular docking simulations of the macromolecular target proteins and their matching ligand molecules, AutoDock Vina and AutoDockTool were utilized.Results: TCMSP identified 162 active target genes and 36 active compounds for WDD. The active target genes were compared with the 2271 genes associated with SD to identify 70 intersecting active target genes linked to 34 active compounds. The GO functional enrichment and KEGG pathway enrichment analyses were undertaken, and compound-target, and PPI networks were built. The key compounds and protein targets were identified and integrated to form a key compound-target network. Eventually, molecular docking was performed to investigate the interactions of the protein targets with their respective compounds.Conclusion: This study highlights the mechanisms of multi-compounds, targets, and pathways of WDD acting on SD and provides further evidence of crucial compounds and their matching target proteins of WDD acting on SD.

Background: LIMA1 encodes LIM domain and actin binding 1, a cytoskeleton-associated protein whose loss has been linked to migration and invasion behavior of cancer cells. However, the roles of LIMA1 underlying the malignant behavior of tumors in head and neck squamous cell carcinoma (HNSC) are not fully understood. Methods: We conducted a multi-omics study on the role of LIMA1 in HNSC based on The Cancer Genome Atlas data. Subsequent in vitro experiments were performed to validate the results of bioinformatic analysis. We first identified the correlation between LIMA1 and tumor cell functional states according to single-cell sequencing data in HNSC. The potential downstream effects of LIMA1 were explored for gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways through functional enrichment analysis of the gene sets that correlated with LIMA1 in HNSC. The prognostic role of LIMA1 was assessed using the log rank test to compare difference in survival between LIMA1(High) and LIMA1(Low) patients. Univariate Cox regression and multivariate Cox regression were further carried out to identify the prognostic value of LIMA1 in HNSC. Results: LIMA1 was identified as a prognostic biomarker and is associated with epithelial-mesenchymal transition (EMT) progress in HNSC. In vitro silencing of LIMA1 suppressed EMT and related pathways in HNSC. Conclusions: LIMA1 promotes EMT and further leads to tumor invasion and metastasis. Increased expression of LIMA1 indicates poor survival, identifying it as a prognostic biomarker in HNSC.

Objective. To explore the effects of resveratrol (RSV) on hair cell apoptosis caused by sudden sensorineural hearing loss (SSNHL) and its effect on lipopolysaccharide-induced apoptosis of HEI-OC1 cells. Methods. We used the network pharmacology method to screen molecules related to RSV for the treatment of SSNHL and analyzed these molecules and their enriched biological processes and signaling pathways through Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis. We selected hub genes related to apoptosis using protein-protein interaction (PPI) analysis for in vitro and molecular docking verification. Results. Eighty overlapping genes were identified as potential targets for RSV treatment of SSNHL. Further GO analysis showed that the biological processes were mainly related to toxicity, cell proliferation, and lipopolysaccharide reactions. KEGG analysis showed that the AGE-RAGE signaling pathway in diabetic complications, Kaposi's sarcoma-associated herpesvirus infection, FoxO signaling pathway, PI3K-Akt signaling pathway, and other inflammatory signaling pathways were concentrated. AKT1, STAT3, JUN, TNF, TP53, MAPK3, CASP3, and VEGFA were screened as HUB genes using PPI analysis. The apoptosis-related proteins TNF, CASP3, AKT1, and TP53 were selected for in vitro experiments, which showed that mRNA was significantly different before and after RSV intervention, confirming that the corresponding protein receptors could bind well with RSV. Conclusion. RSV mainly affects the prognosis of SSNHL through anti-inflammatory effects and may improve hair cell apoptosis caused by inflammatory factors through multitargeted interventions involving TNF, CASP3, AKT1, and TP53.

We used internal transcribed spacer (ITS) sequencing to identify the fungal community in otomycosis patients and to evaluate the treatment effects of bifonazole. Ten patients who visited the Department of Otolaryngology of Jiangsu Provincial Hospital on Integration of Chinese and Western Medicine from May 2020 to April 2021 were recruited. Otomycosis patients were treated with bifonazole solution once a day for 14 days. Samples collected from the external auditory canal before and after treatment (Pre-treatment, n = 14 ears; Post-treatment, n = 14 ears) were used for microscopic examination, fungal culture, and ITS sequencing. Samples collected from 10 volunteers (Control, n = 20 ears) were used as controls. The symptoms, including ear itching, aural fullness, otalgia, hearing loss, and physical signs were recorded before treatment as well as on the 7th and 14th days after treatment. Aspergillus was identified as a main pathogenic fungus by microscopic examination, fungal culture, and ITS sequencing. At the genus level, Aspergillus was more abundant in the pre-treatment group than the control and post-treatment groups, and Malassezia was more abundant in the control and post-treatment groups than the pre-treatment group. The fungal species richness and diversity reduced significantly in the pre-treatment group compared with the control and post-treatment groups. The effective rate of bifonazole was 64.29% and 100% on the 7th and 14th days after treatment, respectively. In conclusion, the results obtained from morphologic studies and ITS sequencing indicate that Aspergillus is the main pathogenic fungus of otomycosis patients in Nanjing, Jiangsu Province, China. Malassezia is the dominant resident fungi in healthy individuals. ITS sequencing provides comprehensive information about fungal community in otomycosis and is helpful in evaluating the efficacy of antifungal agents.

Objective: A retrospective study was conducted to explore the immune-inflammatory responses in sudden sensorineural hearing Loss (SSNHL) patients with different audiogram shapes. Methods: One hundred and ten inpatients with SSNHL were assigned to 4 subgroups according to the audiogram shape and treated with systemic methylprednisolone. The numbers of white blood cells, neutrophils, lymphocytes, platelets, and monocytes were counted. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and the monocyte-to-lymphocyte ratio (MLR) were calculated and statistically analyzed. Results: Neutrophil-to-lymphocyte ratio, MLR, and systemic immune index (SII) of SSNHL patients were significantly higher than the control group, while PLR was not statistically significant. There were no statistical differences in NLR, PLR, MLR, and SII among the 4 subgroups. Conclusion: Immune-inflammatory response may be a common pathogenesis in all SSNHL patients with different audiogram shapes. The predictive value of these hematologic markers needs further research in the future.

Background: To analyze the clinical efficacy of intratympanic steroid perfusion (ISP) and postauricular steroid injection (PSI) for refractory severe and profound sudden sensorineural hearing loss (SSNHL). Methods: SSNHL patients who failed a conventional treatment with severe to profound hearing loss [pure tone average (PTA, 0.25-8 kHz) > 60 dB] were treated with ISP or PSI plus antioxidant and neurotrophin for 10 consecutive days. Antioxidant and neurotrophin were administrated either intravenously and/or orally. All patients were assigned into the ISP group or the PSI group and followed up for more than three months. The changes in PTA, effective rate and side effects were analyzed in the two groups. Results: Similar hearing improvements and effective rates were observed in the two groups. However, a slightly better efficacy was observed in the PSI group compared to the ISP group. Patients with shorter intervals from onset to treatment had significantly more hearing improvements. The route of antioxidant and neurotrophin administration had no impact on treatment effects. Conclusion: Both ISP and PSI could be used as salvage treatments for refractory SSNHL. These salvage treatments should be started as soon as possible once SSNHL patients fail a conventional treatment.

目的 探讨叙事护理对难治性突发性耳聋患者焦虑抑郁的影响及对改善护患关系的意义.方法 选取2018年1月至2019年6月入院的78例难治性突发性耳聋患者,采取随机数字表法分为对照组39例和研究组39例.对照组按突发性耳聋护理常规干预,研究组在对照组的基础上给予叙事护理干预,入院第1天和出院前1d分别进行叙事护理干预1次,期间每5天干预1次.在患者入院第1天和出院前1d采用焦虑自评量表(SAS)和抑郁自评量表(SDS)进行评价.出院时对两组患者进行护理满意度调查.结果 出院前1d两组SAS和SDS评分均较入院第1天显著降低(P＜0.01),且研究组SAS评分(49.50±2.56 vs 54.50±2.55,t=5.346,P＜0.01)和SDS评分(48.70±1.98vs54.00±1.81,t=12.338,P＜0.01)显著低于对照组.出院时调查,研究组患者护理满意度较对照组有所增高,但差异无统计学意义(92.31％ vs 76.92％,x2=3.545,P＞0.05).结论 叙事护理干预可明显改善难治突发性耳聋患者的焦虑抑郁情绪;一定程度改善患者的护理满意度,能否获得有统计学意义的提高,有待扩大样本量继续观察.

We previously reported that dysregulation of histone deacetylase 2 (Hdac2) was associated with the prognosis of sudden sensorineural hearing loss. However, the underlying molecular mechanisms are poorly understood. In the present study, we developed an acute hearing loss animal model in guinea pigs by infusing lipopolysaccharides (LPS) into the cochlea and measured the expression of Hdac2 in the sensory epithelium. We observed that the level of Hdac2 was significantly decreased in the LPS-infused cochleae. The levels of apoptosis-inhibition genes Bcl-2 and Bcl-xl were also decreased in the cochlea and correlated positively with the levels of Hdac2. Caspase3 or TUNEL-positive spiral ganglion neurons, hair cells, and supporting cells were observed in the LPS-infused cochleae. These in vivo observations were recapitulated in cell culture experiments. Based on bioinformatics analysis, we found miR-204-5p was engaged in the regulation of Hdac2 on Bcl-2. Molecular mechanism experiments displayed that miR-204-5p could be regulated by Hdac2 through interacting with transcription factor Sp1. Taken together, these results indicated that the Hdac2/Sp1/miR-204-5p/Bcl-2 regulatory axis mediated apoptosis in the cochlea, providing potential insights into the progression of acute hearing loss. To our knowledge, the study describes a miRNA-related mechanism for Hdac2-mediated regulation in the cochlea for the first time.

Introduction: A significant number of sensorineural hearing loss (SSNHL) patients had no noticeable hearing improvement after glucocorticoid (GC) treatment. In the present study, we examined expression of the nuclear factor erythroid 2-related factor 2 (NRF2) and histone deacetylase 2 (HDAC2) in peripheral blood mononuclear cells (PBMCs) of refractory SSNHL patients to study the role of NRF2-HDAC2 pathway in GC insensitivity hearing improvement after GC treatment, which is usually referred to as refractory SSNHL or GC insensitivity. Materials and Methods: Forty-four refractory SSNHL patients were treated by intratympanic GC infusion. Hearing was tested in all patients before and after treatment by pure tone hearing test. NRF2/HDAC2 mRNA and protein levels were examined in PBMCs of refractory SSNHL patients before and after treatment. PBMCs from healthy volunteers were used as normal controls. Results: According to the hearing improvement after treatment, patients were assigned into 2 groups: the intratympanic GC sensitive (IGCS) group (hearing recovery ≥15 dB HL) and the intratympanic GC insensitive (IGCI) group (hearing recovery <15 dB HL). Before treatment, the NRF2 mRNA level was lower in all patients than the normal control group. After treatment, NRF2 and HDAC2 mRNA and protein levels were increased in the IGCS group, while no significant change was observed in the IGCI group. Conclusion: Low response of NRF2/HDAC2 proteins is associated with GC insensitivity in SSNHL. We speculate that the NRF2-HDAC2 pathway affects GC sensitivity in SSNHL patients.

This study aimed to explore gene expression profiles that drive malignancy from low- to high-grade head and neck carcinomas (HNC), as well as to analyze their correlations with survival. Gene expressions and clinical data of HNC were downloaded from the Gene Expression Omnibus (GEO) repository. The significantly differential genes (SDGs) between low- and high-grade HNC were screened. Cox regressions were performed to identify prognostic SDGs of progression-free survival (PFS) and disease-specific survival (DSS). The genes were experimentally validated by RT-PCR in clinical tissue specimens. Thirty-five SDGs were identified in 47 low-grade and 30 high-grade HNC samples. Cox regression analyses showed that CXCL14, SLC44A1, and UBD were significantly associated with DSS, and PPP2R2C and SLC44A1 were associated with PFS. Patients were grouped into high-risk or low-risk groups for prognosis based on gene signatures. High-risk patients had significantly shorter DSS and PFS than low-risk patients (P=0.033 and P=0.010, respectively). Multivariate Cox regression showed HPV (P=0.033), lymph node status (P=0.032), and residual status (P<0.044) were independent risk factors for PFS. ROC curves showed the risk score had better efficacy to predict survival both for DSS and PFS (AUC=0.858 and AUC=0.901, respectively). The results showed CXCL14 and SLC44A1 were significantly overexpressed in the low-grade HNC tissues and the UBD were overexpressed in the high-grade HNC tissues. Our results suggested that SDGs had different expression profiles between the low-grade and high-grade HNC, and these genes may serve as prognostic biomarkers to predict survival.

Background - To analyze mechanisms of action of glucocorticoid treatment for endoplasmic reticulum stress (ERS) in sensorineural hearing loss (SNHL), we aimed to evaluate the expression and activation status of the protein kinase RNA-like ER kinase (PERK)-C/EBP homologous protein (CHOP) pathway, which is the major pathway in the ERS. Methods - In the present study, we established an in vitro ERS model using tunicamycin-treated hair-cell-like HEIOC1 cells. The effect of dexamethasone on proliferation inhibition, apoptosis, and ATF4-CHOP pathway in HEIOC1 cells was examined by CCK-8 assay, flow cytometry, western blotting, and reverse transcription PCR, respectively. Results - In HEI-OC1 cells, dexamethasone was shown to significantly reduce the tunicamycin-induced expression of ATF4 and CHOP in the context of sustained viability and proliferation, a therapeutic effect that was reversible by co-treatment with a glucocorticoid antagonist. Conclusion - Dexamethasone can protect hair-cell-like HEI-OC1 cells from ERS damage, which may be one of the mechanisms of action for GCs in SNHL treatment.