Correlation of coagulation states with prognosis of sudden deafness.

Prognosis of sudden deafness remains a challenge in clinics because of inhomogeneity of the disease. Here we report our retrospective study aimed to explore the value of coagulative markers including activated partial thromboplastin time (APTT), prothrombin time (PT), plasma fibrinogen (FIB), and plasma D-dimer in the prognosis of patients. The study included a total of 160 patients, of whom 92 had valid responses, 68 had invalid responses, and 68 had ineffective responses. APTT, PT, and the levels of FIB and D-dimer in serum were compared between the two groups, and their prognostic values were determined in terms of area under the curve (AUC) in receiver operating curve (ROC) analysis, sensitivity, and specificity. The correlations of APTT, PT, and FIB to degree of hearing loss were also assessed. Serum APTT and PT, FIB, and D-dimer levels were lower in patients with sudden deafness who responded poorly to treatments. ROC analysis showed that APTT, PT, FIB, and D-dimer had high AUC, sensitivity, and specificity for nonresponders, particularly when used in combination (AUC = 0.91, sensitivity = 86.76%, and specificity = 82.61%). Patients with a higher degree of hearing loss (>91 dB) also demonstrated significantly lower values of APTT and PT and higher levels of serum FIB and D-dimer than those with a lower degree of hearing loss. Our study demonstrated that APTT, PT, and serum levels of FIB and D-dimer could serve as strong predictors of sudden deafness, potentiating the use of these tests to identify patients who respond poorly to treatments.NEW & NOTEWORTHY Our retrospective study indicated that lower serum APTT and PT levels and higher fibrinogen (FIB) and D-dimer levels are characteristics associated with poor treatment responses among patients with sudden deafness. A combination of these levels had a high accuracy in identifying the nonresponders. APTT, PT, and serum levels of FIB and D-dimer could serve as strong predictors of sudden deafness, potentiating the use of these tests to identify patients who respond poorly to treatments.

Anti-CD47 antibody synergizes with cisplatin against laryngeal cancer by enhancing phagocytic ability of macrophages.

Cisplatin is mainly used in late-stage or recurrent laryngeal cancer patients. However, the effect of the chemotherapy is limited due to cisplatin resistance. Therefore, we explored the synergized role of immunosuppressive mediator with cisplatin in laryngeal cancer. Cancer cells isolated from tissues of patients with laryngeal cancer were treated with cisplatin to screen the potential immunosuppressive mediator, whose synergized effects with cisplatin were explored both in vivo and in vitro. CD47 was selected for its high expression in cisplatin-treated laryngeal cancer cells. Blocking CD47 expression using its neutralizing antibody (aCD47) synergized with cisplatin to increase macrophage phagocytosis in a co-culture system of human epithelial type 2 (Hep-2) cancer cells with tumor-associated macrophages (TAMs). Moreover, aCD47 together with cisplatin prevented tumor growth by inhibiting proliferation of cancer cells and the secretion of proinflammatory cytokines, as well as by inducing the apoptosis of cancer cells and phagocytosis of TAMs in a Hep-2-implanted mouse tumor model. aCD47 synergized with cisplatin against laryngeal cancer by enhancing the phagocytic ability of TAMs, and the combined therapy of cisplatin and aCD47 might serve as a novel therapeutic strategy against laryngeal cancer.

Voice treatment of school-aged children with vocal nodules with ABCLOVE rehabilitation.

BACKGROUND: This study was to explore the effectiveness of the ABCLOVE exercise on school-aged children with vocal nodules after the treatment of budesonide. METHODS: Eighty-six school-aged children with vocal nodules were divided into control and ABCLOVE therapy groups. Subjective voice assessment and dysphonia severity index (DSI) assessment were performed before and after the 3-month of therapy. RESULTS: A significant improvement was observed in the ABCLOVE therapy group as compared with the control group (p = 0.035). ABCLOVE therapy significantly reduced the hoarseness and roughness scores in school-aged children with vocal nodules. Additionally, a significant reduction in functional score, physical score, emotional score, and total pVHI score was observed in the ABCLOVE therapy group. Moreover, acoustic parameters including jitter (%) and shimmer (%) were significantly reduced, whereas MPT and DSI were increased in school-aged children with vocal nodules who received 3 months of ABCLOVE treatment. CONCLUSION: ABCLOVE therapy displayed effectiveness on school-aged children with vocal nodules after the treatment of budesonide.

Correlation of acoustic voice analysis and Voice Handicap Index in patients with postoperative unilateral vocal cord paralysis after thyroid surgery.

Unilateral vocal cord paralysis is frequently observed in patients who undergo thyroid surgery. This study explored the correlation between acoustic voice analysis (objective measure) and Voice Handicap Index (VHI, a self-assessment tool). One hundred and forty patients who had thyroid surgery with or without postoperative unilateral vocal cord paralysis (PVCP and NPVCP) were included. The patients were evaluated by the VHI and Dysphonia Severity Index (DSI) tools. VHI scores were significantly higher in PVCP patients than in NPVCP patients. Jitter (%) and shimmer (%) were significantly increased, whereas DSI was significantly decreased in PVCP patients. Receiver operating characteristics curve revealed that VHI scores were associated with the diagnosis of PVCP, of which VHI total score yielded an area under the curve (AUC) of 0.81. Among acoustic parameters, DSI was highly associated to PVCP (AUC=0.82, 95%CI=0.75 to 0.89). Moreover, we found a correlation between VHI scores and voice acoustic parameters. Among them, DSI had a moderate correlation with functional and VHI scores, as suggested by an R value of 0.41 and 0.49, respectively. VHI scores and acoustic parameters were associated with the diagnosis of PVCP.

lncRNA FLJ20021 regulates CDK1-mediated PANoptosis in a ZBP1-dependent manner to increase the sensitivity of laryngeal cancer-resistant cells to cisplatin.

In this study, we investigated the role of the newly discovered lncRNA FLJ20021 in laryngeal cancer (LC) and its resistance to cisplatin treatment. We initially observed elevated lncRNA FLJ20021 levels in cisplatin-resistant LC cells (Hep-2/R). To explore its function, we transfected lncRNA FLJ20021 and cyclin-dependent kinase 1 (CDK1) into Hep-2/R cells, assessing their impact on cisplatin sensitivity and PANoptosis. Silencing lncRNA FLJ20021 effectively reduced cisplatin resistance and induced PANoptosis in Hep-2/R cells. Mechanistically, lncRNA FLJ20021 primarily localized in the nucleus and interacted with CDK1 mRNA, thereby enhancing its transcriptional stability. CDK1, in turn, promoted panapoptosis in a ZBP1-dependent manner, which helped overcome cisplatin resistance in Hep-2/R cells. This study suggests that targeting lncRNA FLJ20021 can be a promising approach to combat cisplatin resistance in laryngeal cancer by regulating CDK1 and promoting PANoptosis via the ZBP1 pathway. These findings open up possibilities for lncRNA-based therapies in the context of laryngeal cancer.

Oxaliplatin Induces Immunogenic Cell Death in Human and Murine Laryngeal Cancer.

Background: Cisplatin resistance is observed in patients with laryngeal cancer. The present study was designed to explore the efficacy of oxaliplatin on laryngeal cancer and elucidate the underlying mechanisms. Methods: Cell viability was determined by using MTT assays. Cell apoptosis was determined by using annexin V and propidium iodide (PI) staining. Flow cytometry and immunofluorescence were applied to determine the levels of calreticulin (CALR) and DiD (1,1-dioctadecyl-3,3,3,3-tetramethylindodicarbocyanine). Flow cytometry was applied to analyze the levels of CD83, CD86, IFN-γ-producing CD8+ T cells, and CD4+CD25+FoxP3+ Tregs. The levels of adenosine triphosphate (ATP) were determined by using a chemiluminescent ATP kit and cytokines were determined by using specific enzyme-linked immunosorbent assays (ELISAs). The levels of HMGB1 were determined by using Western blot and ELISA, respectively. The xenograft animal model was constructed to evaluate the antitumor effects of oxaliplatin. Results: Oxaliplatin inhibited cell growth, promoted cell apoptosis, and induced the levels of CALR, ATP, and high mobility group box protein 1 (HMGB1) in Hep-2 cells. Oxaliplatin-treated Hep-2 cells increased the intensity of DiD and the levels of CD83 and CD86 in dendritic cells (DCs), as well as induced the supernatant IL-6 and TNF-α. Oxaliplatin-treated primary laryngeal cancer cell-pulsed DCs increased the IFN-γ-producing CD8+ T cells and suppressed CD4+CD25+FoxP3+ Tregs. In vivo data showed that oxaliplatin suppressed tumor growth and increased the populations of CD86+CD80+ and CD8+CD45+ cells in the tumor tissues. Conclusion: Treatment with oxaliplatin inhibited laryngeal cancer cells by inducing immunogenic cell death.

CAPRIN1 Enhances Chemoresistance and Glycolysis in Laryngeal Squamous Cell Carcinoma via Regulation of ZIC5.

Background: Cytoplasmic activation/proliferation-associated protein-1 (CAPRIN1) plays an important role in carcinogenesis, whereas its role in laryngeal squamous cell carcinoma remains unclear. This study was designed to investigate the roles of CAPRIN1 in glycolysis and chemoresistance and its underlying mechanisms in laryngeal squamous cell carcinoma. Methods: Cell viability was evaluated by using CCK-8 and colony formation assays. qRT-PCR, Western blotting, and immunohistochemistry were used to determine the expressions of target genes. Gene knockdown and overexpression cell lines were constructed by performing transfection of siRNAs and plasmids, respectively. Luciferase reporter assay, RNA pull-down, and RNA immunoprecipitation assays were applied to evaluate the RNA-protein interactions. The Kaplan-Meier analysis was performed to evaluate the relationship between gene expression and overall survival rate. Results: An elevation of CAPRIN1 was identified to be associated with chemoresistance and poor prognosis in patients with laryngeal cancer. The increase of CAPRIN1 promoted glycolysis and chemoresistance, whereas the knockdown of CAPRIN1 inhibited glycolysis and chemoresistance in laryngeal cancer cells. The underlying mechanistic investigation revealed that CAPRIN1 promoted glycolysis and chemoresistance of laryngeal cancer cells by the regulation of Zic Family Member 5 (ZIC5). Conclusion: CAPRIN1 promoted laryngeal squamous cell carcinoma glycolysis and chemoresistance by the regulation of ZIC5.

Comprehensive Analysis of LINC01615 in Head and Neck Squamous Cell Carcinoma: A Hub Biomarker Identified by Machine Learning and Experimental Validation.

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers, but in clinical practice, the lack of precise biomarkers often results in an advanced diagnosis. Hence, it is crucial to explore novel biomarkers to improve the clinical outcome of HNSCC patients. Methods: We downloaded RNA-seq data consisting of 502 HNSCC tissues and 44 normal tissues from the TCGA database, and lncRNA genomic sequence information was downloaded from the GENECODE database for annotating lncRNA expression profiles. We used Cox regression analysis to screen prognostic lncRNAs, the threshold as HR >1 and p value <0.05. Subsequently, three survival outcomes (overall survival, progress-free interval, and disease-specific survival)-related lncRNAs overlapped to get the common lncRNAs. The hub biomarker was identified using LASSO and random forest models. Subsequently, we used a variety of statistical methods to validate the prognostic ability of the hub marker. In addition, Spearman correlation analysis between the hub marker expression and genomic heterogeneity was conducted, such as instability (MSI), homologous recombination deficiency (HRD), and tumor mutational burden (TMB). Finally, we used enrichment analysis, ssGSEA, and ESTIMATE algorithms to explore the changes in the underlying immune-related pathway and function. Finally, the MTT assay and transwell assay were performed to determine the effect of LINC01615 silencing on tumor cell proliferation, invasion, and migration. Results: Cox regression analysis revealed 133 lncRNAs with multiple prognostic significance. The machine learning algorithm screened out the hub lncRNA with the highest importance in the RF model: LINC01615. Clinical correlation analysis revealed that the LINC01615 increased with increasing the T stage, N stage, pathology grade, and clinical stage. LINC01615 could be used as a predictor of HNSCC prognosis validating by a variety of statistical methods. Subsequently, when clinical indicators were combined with the LINC01615 expression, the visualization model (nomogram) was more applicable to clinical practice. Finally, immune algorithms indicated that LINC01615 may be involved in the regulation of lymphocyte recruitment and immunological infiltration in HNSCC, and the LINC01615 expression represented genomic heterogeneity in pan-cancer. Functionally, silencing of LINC01615 suppresses cell proliferation, invasion, and migration in HEP-2 and TU212 cells. Conclusion: LINC01615 may play an important role in the prostromal cell enrichment and immunosuppressive state and serve as a prognostic biomarker in HNSCC.

Circular RNA ZNF609 promotes laryngeal squamous cell carcinoma progression by upregulating epidermal growth factor receptor via sponging microRNA-134-5p.

Emerging evidence has revealed that aberrantly expressed circular RNAs (circRNAs) play vital roles in tumorigenesis and progression of diverse human malignancies. CircZNF609 was found to be involved in hepatocellular carcinoma, but the role and underlying mechanism of circZNF609 in laryngeal squamous cell carcinoma (LSCC) remain unclear. This study aimed to explore the molecular mechanism of circZNF609 in LSCC. qRT-qPCR was performed to detect the expression of circZNF609 and microRNA-134-5p (miR-134-5p) in LSCC. Colony formation assay, CCK-8 assay, BrdU incorporation assay, clone formation assay, transwell invasion assay and Western blot analysis were performed to evaluate LSCC cell proliferation, as well as the expression of proliferating cell nuclear antigen (PCNA) and MMP-2. Luciferase reporter assay, target gene prediction and screening were used to validate downstream target genes of circZNF609 and miR-134-5p. EGFR expression was detected by Western blot analysis and RT-qPCR. Nude mice were used to detect tumor changes. CircZNF609 was upregulated in LSCC and associated with poor survival of LSCC patients. Knockdown of circZNF609 inhibited LSCC proliferation, invasion and the expression of PCNA and matrix matalloproteinases-2 (MMP-2). CircZNF609 can regulate miR-134-5p to upregulate epidermal growth factor receptor (EGFR). In addition, knockdown of EGFR or overexpression of miR-134-5p could reverse the tumor-promoting effects of circZNF609 in LSCC. In LSCC tissues, circZNF609 was negatively correlated with miR-134-5p and positively correlated with EGFR. CircZNF609 promotes the progression of LSCC via the miR-134-5p/EGFR axis, which might be the therapeutic target of LSCC.

Correlation of acoustic voice analysis and Voice Handicap Index in patients with postoperative unilateral vocal cord paralysis after thyroid surgery

Unilateral vocal cord paralysis is frequently observed in patients who undergo thyroid surgery. This study explored the correlation between acoustic voice analysis (objective measure) and Voice Handicap Index (VHI, a self-assessment tool). One hundred and forty patients who had thyroid surgery with or without postoperative unilateral vocal cord paralysis (PVCP and NPVCP) were included. The patients were evaluated by the VHI and Dysphonia Severity Index (DSI) tools. VHI scores were significantly higher in PVCP patients than in NPVCP patients. Jitter (%) and shimmer (%) were significantly increased, whereas DSI was significantly decreased in PVCP patients. Receiver operating characteristics curve revealed that VHI scores were associated with the diagnosis of PVCP, of which VHI total score yielded an area under the curve (AUC) of 0.81. Among acoustic parameters, DSI was highly associated to PVCP (AUC=0.82, 95%CI=0.75 to 0.89). Moreover, we found a correlation between VHI scores and voice acoustic parameters. Among them, DSI had a moderate correlation with functional and VHI scores, as suggested by an R value of 0.41 and 0.49, respectively. VHI scores and acoustic parameters were associated with the diagnosis of PVCP.