Primary squamous cell carcinoma of thyroid gland: 11 case reports and a population-based study.

BACKGROUND: Primary squamous cell carcinoma of thyroid gland (PSCCT) is a highly aggressive malignant tumor associated with a poor prognosis. Due to the rare case, there is a knowledge gap on the features of PSCCT. There is limited understanding of the treatment and molecular biology of this tumor. More genomic work and relevant perspective work need to be done. METHODS: We retrospectively reviewed the medical information of patients with PSCCT diagnosed from December 2009 to December 2020 at The First Affiliated Hospital of Guangxi Medical University. In addition, we conducted an electronic search of the paper in CNKI, Wanfang, VIP, PubMed, Embase, Web of Science, and ProQuest databases by recently updated articles. Survival analysis was conducted using the Kaplan-Meier method. RESULTS: There were only 11 patients met the study's inclusion criteria in our institution. The patients ranged in age from 25 to 68 years old and female preponderance (M:F = 1:1.7). The median survival time was 6 months, and 1-year survival rate was 33.3%. Fifty-three patients' individual data from 45 articles were selected for analysis. The median age at diagnosis was 63 years and female preponderance (M:F = 1:2.5). The commonest complaint was the anterior neck mass (77.3%), followed by hoarseness (32.1%). The median survival time was 9 months, and the overall 1-, 2-, and 5-year survival rate was 39.8%, 33.7%, and 26.9%, respectively. The log-rank method shows that age, tumor size, lymph node status, M stage, surgical range, and tracheal status were the relevant factors affecting the prognosis. In contrast, gender, treatment modality, and resection margin were not prognostic factors. On multivariable analysis, age and M stage were associated with overall survival. CONCLUSION: The median overall survival was 6-9 months of PSCCT. Age and M stage are predictors of PSSCT.

Acylglycerol kinase promotes paclitaxel resistance in nasopharyngeal carcinoma cells by regulating FOXM1 via the JAK2/STAT3 pathway.

OBJECTIVE: Drug resistance is an important factor that impedes the treatment of nasopharyngeal cancer (NPC). Acylglycerol kinase (AGK) has been found to be overexpressed in NPC and correlates with poor prognosis. Our objective was to demonstrate the effect of AGK on paclitaxel resistance in NPC and determine the underlying mechanisms. METHODS: MTT assay was employed to determine the IC50 of paclitaxel in NPC cells after different treatments. Flow cytometry assays were employed to evaluate cell apoptosis. RT-qPCR and Western blot assays were used to detect alterations in mRNA and protein expression, respectively. Luciferase assays and chromatin immunoprecipitation (ChIP) assays were used to determine the relationship between and the regulatory effect of STAT3 on the promoter of FOXM1. RESULTS: AGK was elevated in paclitaxel-resistant NPC cells, and knockdown of AGK suppressed the resistance of CNE1-TR and CNE2-TR cells to paclitaxel. Moreover, upregulation of FOXM1 rescued the effects of AGK knockdown. Furthermore, the JAK2/STAT3 signalling pathway was overactivated in CNE1-TR and CNE2-TR cells, and knockdown of AGK suppressed JAK2/STAT3 signalling. STAT3 was verified to bind to and activate the promoter region of FOXM1. An in vivo tumour xenograft assay also verified that AGK knockdown inhibited tumour growth and mitigated paclitaxel resistance by regulating the JAK2/STAT3/FOXM1 axis. CONCLUSION: AGK levels were increased in paclitaxel-resistant NPC cells. AGK activates JAK2/STAT3 signalling, thus promoting FOXM1 transcription and eventually enhancing the drug resistance of NPC cells.

Salicylate Induced GABAAR Internalization by Dopamine D1-Like Receptors Involving Protein Kinase C (PKC) in Spiral Ganglion Neurons.

BACKGROUND Sodium salicylate (SS) induces excitotoxicity of spiral ganglion neurons (SGNs) by inhibiting the response of γ-aminobutyric acid type A receptors (GABAARs). Our previous studies have shown that SS can increase the internalization of GABAARs on SGNs, which involves dopamine D1-like receptors (D1Rs) and related signaling pathways. In this study, we aimed to explore the role of D1Rs and their downstream molecule protein kinase C (PKC) in the process of SS inhibiting GABAARs. MATERIAL AND METHODS The expression of D1Rs and GABARγ2 on rat cochlear SGNs cultured in vitro was tested by immunofluorescence. Then, the SGNs were exposed to SS, D1R agonist (SKF38393), D1R antagonist (SCH23390), clathrin/dynamin-mediated endocytosis inhibitor (dynasore), and PKC inhibitor (Bisindolylmaleimide I). Western blotting and whole-cell patch clamp technique were used to assess the changes of surface and total protein of GABARγ2 and GABA-activated currents. RESULTS Immunofluorescence showed that D1 receptors (DRD1) were expressed on SGNs. Data from western blotting showed that SS promoted the internalization of cell surface GABAARs, and activating D1Rs had the same result. Inhibiting D1Rs and PKC decreased the internalization of GABAARs. Meanwhile, the phosphorylation level of GABAARγ2 S327 affected by PKC was positively correlated with the degree of internalization of GABAARs. Moreover, whole-cell patch clamp recording showed that inhibition of D1Rs or co-inhibition of D1Rs and PKC attenuated the inhibitory effect of SS on GABA-activated currents. CONCLUSIONS D1Rs mediate the GABAAR internalization induced by SS via a PKC-dependent manner and participate in the excitotoxic process of SGNs.

Neurotoxicity of sodium salicylate to the spiral ganglion neurons: GABAA receptor regulates NMDA receptor by Fyn-dependent phosphorylation.

The purpose of this study was to observe the regulatory effects of GABAA (γ-aminobutyric acid A) receptor on the N-methyl-D-aspartate (NMDA) receptor during excitotoxicity in spiral ganglion neurons in the rat cochlea induced by sodium salicylate (SS). Western blot illustrated SS decreased the expression of NMDA receptor 2B subunit (NR2B) surface protein through affecting GABAA receptor, but the total protein content did not significantly change. Y1472 and S1480 are important phosphorylation sites in NR2B, SS downregulated the Fyn-dependent phosphorylation of Y1472 in a manner not related to the CK2 (Casein Kinase 2) dependent phosphorylation of S1480, thus regulating the surface distribution and internalization of NMDA receptor through GABAA receptor. These results suggest that the modified pattern of dynamic balance between excitation and inhibition by coactivation of the GABAA receptor can attenuate the excitatory NMDA receptor under the action of SS, via inhibiting the Fyn-dependent phosphorylation of Y1472.

[A study on toxic effects of sodium salicylate on rat cochlear spiral ganglion neurons: dopamine receptors mediate expressions of NMDA and GABAA receptors].

The aim of the present study was to observe whether dopamine receptor (DR) was involved in the effects of sodium salicylate (SS) on the expressions of N-methyl-D-aspartic acid (NMDA) and γ-aminobutyric acid (GABA) receptors in rat cochlear spiral ganglion neurons (SGNs). Forty-eight hours after primary culture of rat SGNs, immunofluorescence technique was applied to detect expressions of DR1 and DR2, the two subtypes of dopamine receptors. Western blot was performed to assess NMDA receptor NR1 subunit and GABAA receptor subunit α2 (GABRα2) protein expressions in the SGNs after the treatments of SS alone or in combination with DR antagonists. The results demonstrated that: (1) The DR1 and DR2 were expressed in the bodies and axons of the SGN; (2) After the treatment with SS, the surface protein expressions of GABRα2 and NR1 were decreased by 44.69% and 21.57%, respectively, while the total protein expressions showed no significant changes; (3) Neither SS + SCH23390 (DR1 antagonist) group nor SS + Eticlopride (DR2 antagonist) group showed significant differences in GABRα2 and NR1 surface protein expressions compared with the control group. These results suggest that SS regulates the surface GABAA and NMDA receptors trafficking on SGN, and the mechanism may involve DR mediation.

Src family tyrosine kinase inhibitors suppress Nav1.1 expression in cultured rat spiral ganglion neurons.

Src family kinases regulate neuronal voltage-gated Na(+) channels, which generate action potentials. The mechanisms of action, however, remain poorly understood. The aim of the present study was to further elucidate the effects of Src family kinases on Nav1.1 mRNA and protein expression in spiral ganglion neurons. Immunofluorescence staining techniques detected Nav1.1 expression in the spiral ganglion neurons. Additionally, quantitative PCR and western blot techniques were used to analyze Nav1.1 mRNA and protein expression, respectively, in spiral ganglion neurons following exposure to Src family kinase inhibitors PP2 (1 and 10 µM) and SU6656 (0.1 and 1 µM) for different lengths of time (6 and 24 h). In the spiral ganglion neurons, Nav1.1 protein expression was detected in the somas and axons. The Src family kinase inhibitors PP2 and SU6665 significantly decreased Nav1.1 mRNA and protein expression (p < 0.05), respectively, in the spiral ganglion neurons, and changes in expression were not dependent on time or dose (p > 0.05).

[Interactions between dopamine receptor and NMDA/type A γ-aminobutyric acid receptors].

Type A γ-aminobutyric acid receptors (GABAAR) and N-methyl-D-aspartate receptors (NMDAR) are the major inhibitory and excitatory receptors in the central nervous system, respectively. Co-expression of the receptors in the synapse may lead to functional influence between receptors, namely receptor interaction. The interactions between GABAAR and NMDAR can be either positive or negative. However, the mechanisms of interaction between the two receptors remain poorly understood, and potential mechanisms include (1) through a second messenger; (2) by receptors trafficking; (3) by direct interaction; (4) by a third receptor-mediation. Dopamine is the most abundant catecholamine neurotransmitter in the brain, and its receptors, dopamine receptors (DR) can activate multiple signaling pathways. Earlier studies on the interaction between DR and GABAAR/NMDAR have shown some underlying mechanisms, suggesting that DR could mediate the interaction between GABAAR and NMDAR. This paper summarized some recent progresses in the studies of the interaction between DR and NMDAR/GABAAR, providing a further understanding on the interaction between NMDAR and GABAAR mediated by DR.

Increased phosphatidylcholine (16:0/16:0) in the folliculus lymphaticus of Warthin tumor.

Warthin tumor (War-T), the second most common benign salivary gland tumor, consists mainly of neoplastic epithelium and lymphoid stroma. Some proteins and genes thought to be involved in War-T were evaluated by molecular biology and immunology. However, lipids as an important component of many tumor cells have not been well studied in War-T. To elucidate the molecular biology and pathogenesis of War-T, we investigated the visualized distribution of phosphatidylcholines (PCs) by imaging mass spectrometry (IMS). In our IMS analysis of a typical case, 10 signals were significantly different in intensity (p < 0.01) between the War-T and non-tumor (Non-T) regions. Five specific PCs were frequently found in the War-T regions of all of the samples: [PC (16:0/16:0) + K](+) (m/z 772.5), [PC (16:0/20:4) + K](+) (m/z 820.5), [PC (16:0/20:3) + K](+) (m/z 822.5), [PC (18:2/20:4) + K](+) (m/z 844.5), and [PC (18:0/20:5) + K](+) (m/z 846.5). PC (16:0/16:0) was increased specifically in the folliculus lymphaticus of War-T lymphoid stroma, suggesting a different metabolism. Localization of PC (16:0/16:0) might reflect inflammation activity participating in the pathogenesis of War-T. Thus, our IMS analysis revealed the profile of PCs specific to the War-T region. The molecules identified in our study provide important information for further studies of War-T pathogenesis.

HSP90B1 regulates autophagy via PI3K/AKT/mTOR signaling, mediating HNSC biological behaviors.

Background: Autophagy, a crucial cellular mechanism, facilitates the degradation and removal of misfolded proteins and impaired organelles. Recent research has increasingly highlighted the intimate connection between autophagy and heat shock proteins (HSPs) in the context of tumor development. However, the specific role and underlying mechanisms of heat shock protein 90 beta family member 1 (HSP90B1) in modulating autophagy within head and neck squamous cell carcinoma (HNSCC) remain elusive. Methods: Quantitative real-time PCR (qRT-PCR), Western blot (WB), immunohistochemistry (IHC) were used to detect the expression in HNSC cell lines and tissues. The relationship between HSP90B1 and clinicopathologic features was explored based on TCGA (The Cancer Genome Atlas) data and IHC results. The biological functions of HSP90B1 were analyzed through in vitro and in vivo models to evaluate proliferation, migration, invasion, and autophagy. The mechanisms of HSP90B1 were studied using bioinformatics and WB. Results: HSP90B1 was upregulated in HNSC cells and tissues. High HSP90B1 levels were associated with T-stage, M-stage, clinical stage, and poor prognosis in HNSC patients. Functionally, HSP90B1 promotes HNSC cell proliferation, migration, invasion and inhibits apoptosis. We discovered that HSP90B1 obstructs autophagy and advances HNSC progression through the PI3K/Akt/mTOR pathway. Conclusion: Our study demonstrates that HSP90B1 is highly expressed in HNSC. Furthermore, HSP90B1 may regulate autophagy through the PI3K/Akt/mTOR pathway, mediating HNSC cell biological behaviors. These provide new insights into potential biomarkers and targets for HNSC therapy.

POSTN Regulates Fibroblast Proliferation and Migration in Laryngotracheal Stenosis Through the TGF-ß/RHOA Pathway.

OBJECTIVES: To investigate the role of periostin (POSTN) and the transforming growth factor ß (TGF-ß) pathway in the formation of laryngotracheal stenosis (LTS) scar fibrosis and to explore the specific signaling mechanism of POSTN-regulated TGF-ß pathway in tracheal fibroblasts. METHODS: Bioinformatics analysis was performed on scar data sets from the GEO database to preliminarily analyze the involvement of POSTN and TGF-ß pathways in fibrosis diseases. Expression of POSTN and TGF-ß pathway-related molecules was analyzed in LTS scar tissue at the mRNA and protein levels. The effect of POSTN on the biological behavior of tracheal fibroblasts was studied using plasmid DNA overexpression and siRNA silencing techniques to regulate POSTN expression and observe the activation of TGF-ß1 and the regulation of cell proliferation and migration via the TGF-ß/RHOA pathway. RESULTS: The bioinformatics analysis revealed that POSTN and the TGF-ß pathway are significantly involved in fibrosis diseases. High expression of POSTN and TGF-ß/RHOA pathway-related molecules (TGFß1, RHOA, CTGF, and COL1) was observed in LTS tissue at both mRNA and protein levels. In tracheal fibroblasts, overexpression or silencing of POSTN led to the activation of TGF-ß1 and regulation of cell proliferation and migration through the TGF-ß/RHOA pathway. CONCLUSION: POSTN is a key molecule in scar formation in LTS, and it regulates the TGF-ß/RHOA pathway to mediate the formation of cicatricial LTS by acting on TGF-ß1. This study provides insights into the molecular mechanisms underlying LTS and suggests potential therapeutic targets for the treatment of this condition. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

A nomogram for distinguishing benign and malignant parotid gland tumors using clinical data and preoperative blood markers: development and validation.

PURPOSE: This study aimed to construct and validate a nomogram that incorporated clinical data and preoperative blood markers to differentiate BPGTs from MPGTs more efficiently and at low cost. METHODS: We retrospectively analyzed patients who underwent parotidectomy and histopathological diagnosis at the First Affiliated Hospital of Guangxi Medical University from January 2013 to June 2022. Subjects were randomly divided into training and validation sets with a 7:3 ratio. In the training set, the least absolute shrinkage and selection operator (LASSO) regression analysis was performed to select the most relevant features from 19 variables and built a nomogram using logistic regression. We evaluated the model's performance using receiver-operating characteristic (ROC) curves, calibration curves, clinical decision curve analysis (DCA), and clinical impact curve analysis (CICA). RESULTS: The final sample consisted of 644 patients, of whom 108 (16.77%) had MPGTs. The nomogram included four features: current smoking status, pain/tenderness, peripheral facial paralysis, and lymphocyte-to-monocyte ratio (LMR). The optimal cut-off value for the nomogram was 0.17. The areas under the ROC curves (AUCs) of the nomogram were 0.748 (95% confidence interval [CI] = 0.689-0.807) and 0.754 (95% CI = 0.636-0.872) in the training and validation sets, respectively. The nomogram also showed good calibration, high accuracy, moderate sensitivity, and acceptable specificity in both sets. The DCA and CICA demonstrated that the nomogram had significant net benefits for a wide range of threshold probabilities (0.06-0.88 for the training set; 0.06-0.57 and 0.73-0.95 for the validation set). CONCLUSION: The nomogram based on clinical characteristics and preoperative blood markers was a reliable tool for discriminating BPGTs from MPGTs preoperatively.

Sterol regulatory element binding transcription factor 1 promotes proliferation and migration in head and neck squamous cell carcinoma.

Background: Sterol-regulatory element-binding protein 1 (SREBP1) is a transcription factor involved in lipid metabolism that is encoded by sterol regulatory element binding transcription factor 1(SREBF1). SREBP1 overexpression is associated with the progression of several human tumors; however, the role of SREBP1 in head and neck squamous cell carcinoma (HNSC) remains unclear. Methods: SREBF1 expression in pan-cancer was analyzed using the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data, and the association between SREBF1 expression and clinical characteristics of HNSC patients was examined using the UALCAN database. Enrichment analysis of SREBF1-related genes was performed using the Cluster Profiler R package. TCGA database was used to investigate the relationship between immune cell infiltration and SREBF1 expression. CCK-8, flow cytometry, and wound healing assays were performed to investigate the effect of SREBF1 knockdown on the proliferation and migration of HNSC cells. Results: SREBF1 was significantly upregulated in several tumor tissues, including HNSC, and SREBF1 overexpression was positively correlated with sample type, cancer stage, tumor grade, and lymph node stage in HNSC patients. Gene enrichment analysis revealed that SREBF1 is associated with DNA replication and homologous recombination. SREBF1 upregulation was positively correlated with the infiltration of cytotoxic cells, B cells, T cells, T helper cells, and NK CD56 bright cells in HNSC. Knockdown of SREBF1 inhibited the proliferation and migration of HNSC cells (Hep2 and TU212) and induced apoptosis by downregulating the expression of steroidogenic acute regulatory protein-related lipid transfer 4 (STARD4). Conclusions: SREBF1 may promote HNSC proliferation, migration and inhibit apoptosis by upregulating STARD4 and affecting the level of immune cell infiltration.

Melatonin Suppresses Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Signaling and Delays the Development of Hearing Loss in the C57BL/6J Presbycusis Mouse Model.

Melatonin supplementation has been shown to delay age-related hearing loss (ARHL) progression. Previously, melatonin was found to inhibit neuronal mitochondrial DNA (mtDNA) release, as well as inhibit cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling, thereby delaying the onset of central nervous system diseases. Therefore, we hypothesized that melatonin may delay the progression of hearing loss in the C57BL/6J presbycusis mouse model by inhibiting cGAS-STING signaling in the auditory pathway. Oral melatonin at 10 mg/kg/d was administered to 3-month-old C57BL/6J mice until 12 months of age. The auditory brainstem response (ABR) threshold was used to assess their hearing ability. By real-time polymerase chain reaction and Western blot analysis, the levels of cytosolic mtDNA, cGAS/STING, and cytokines were examined in the mouse cochlea, inferior colliculus, and auditory cortex. We found that the 12-month-old control mice exhibited significant hearing loss, increased cytosolic mtDNA, increased expression of inflammatory factors TNF-α, IL-6, IFN-ß, Cxcl10, and Ifit3, up-regulated cGAS and STING expression, and enhanced interferon regulatory factor 3 (IRF3) phosphorylation in the C57BL/6J mouse cochlea, inferior colliculus, and auditory cortex. Melatonin treatment significantly improved hearing, decreased cytosolic mtDNA, suppressed the expression of inflammatory cytokines TNF-α, IL-6, IFN-ß, Ifit3, and Cxcl10, down-regulated cGAS and STING expression, and attenuated IRF3 phosphorylation in the C57BL/6J mouse cochlea, inferior colliculus, and auditory cortex. This study suggested that melatonin had a protective effect on auditory function in the C57BL/6J presbycusis mouse model, which may be mediated through reducing mtDNA release, inhibiting the cGAS-STING signaling pathway in the auditory pathway.

Regulation of voltage-gated sodium current by endogenous Src family kinases in cochlear spiral ganglion neurons in culture.

Voltage-gated sodium (Na+) and potassium (K+)channels have been found to be regulated by Src family kinases(SFKs).However, how these channels are regulated by SFKs in cochlear spiral ganglion neurons (SGNs) remains unknown.Here, we report that altering the activity of endogenous SFKs modulated voltage-gated Na+, but not K+, currents recorded in embryonic SGNs in culture. Voltage-gated Na+ current was suppressed by inhibition of endogenous SFKs or just Src and potentiated by the activation of these enzymes. Detailed investigations showed that under basal conditions, SFK inhibitor application did not significantly affect the voltage-dependent activation, but shifted the steady-state inactivation curves of Na+ currents and delayed the recovery of Na+ currents from inactivation. Application of Src specific inhibitor, Src40­58,not only shifted the inactivation curve but also delayed the recovery of Na+ currents and moved the voltage-dependent activation curve towards the left. The pre-inhibition of SFKs occluded all the effects induced by Src40­58 application, except the left shift of the activation curve. The activation of SFKs did not change either steady-state inactivation or recovery of Na+ currents, but caused the left shift of the activation curve.SFK inhibitor application effectively prevented all the effects induced by SFK activation, suggesting that both the voltage-dependent activation and steady-state inactivation of Na+ current are subjects of SFK regulation. The different effects induced by activation versus inhibition of SFKs implied that under basal conditions, endogenously active and inactive SFKs might be differentially involved in the regulation of voltage-gated Na+ channels in SGNs.

Age-related Activation of Cyclic GMP-AMP synthase-Stimulator of Interferon Genes Signaling in the Auditory System is Associated with Presbycusis in C57BL/6J Male Mice.

Presbycusis, or age-related hearing loss (ARHL), is primarily associated with sensory or transduction nerve cell degeneration in the peripheral and/or central auditory systems. During aging, the auditory system shows mitochondrial dysfunction and increased inflammatory responses. Mitochondrial dysfunction promotes leakage of mitochondrial DNA (mtDNA) into the cytosol, which activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway to induce type I interferon and inflammatory responses. However, whether this pathway is involved in the occurrence and development of ARHL is unknown. This study aimed to determine whether there are age-related changes in the levels of cytosolic mtDNA and cGAS-STING pathway activation in the auditory pathway and to explore their relationship with ARHL. The results showed that cGAS-positive immunoreactive cells were observed in the cochlea, inferior colliculus, and auditory cortex. Levels of cytosolic mtDNA, cGAS, STING, phosphorylated interferon regulatory factor 3, and cytokines were significantly increased in the cochlea, inferior colliculus, and auditory cortex of 6-, 9-, and 12-month-old mice compared with 3-month-old mice. These findings suggested that cytosolic mtDNA may play an important role in the pathogenesis of ARHL by activating cGAS-STING-mediated type I interferon and inflammatory responses.

lncRNA NR2F2-AS1 inhibits the methylation of miR-494 to regulate oral squamous cell carcinoma cell proliferation.

OBJECTIVE: This study aimed to investigate the role of lncRNA NR2F2-AS1 in oral squamous cell carcinoma cells (OSCC). MATERIALS AND METHODS: The TCGA datasets were used to explore the differential expression of NR2F2-AS1 in OSCC. To further explore the potential interaction between NR2F2-AS1 and miR-494, SCC090 cells were transfected with the NR2F2-AS1 expression vector, NR2F2-AS1 siRNA, and a miR-494 mimic. The effect of NR2F2-AS1 on miR-494 methylation was evaluated by performing methylation-specific PCR (MSP). Cell Counting Kit-8 (CCK-8) assay was used to assess the effects of NR2F2-AS1 silencing and miR-494 and NR2F2-AS1 overexpression on OSCC cell proliferation. RESULTS: NR2F2-AS1 expression was downregulated in OSCC and positively correlated with miR-494 expression. In OSCC cells, NR2F2-AS1 overexpression upregulated miR-494 level, while NR2F2-AS1 silencing decreased miR-494 expression. MSP results showed that NR2F2-AS1 overexpression decreased miR-494 methylation while NR2F2-AS1 silencing increased miR-494 methylation. In addition, NR2F2-AS1 silencing increased OSCC cell proliferation rate while overexpression of miR-494 and NR2F2-AS1 decreased OSCC cell proliferation. Furthermore, miR-494 overexpression attenuated the effects of NR2F2-AS1 silencing on cell proliferation. CONCLUSION: NR2F2-AS1 may inhibit miR-494 methylation to regulate cell proliferation in OSCC. AVAILABILITY OF DATA AND MATERIALS: The analyzed data sets generated during the study are available from the corresponding author upon reasonable request.

Fluid dynamics of the upper airway in pediatric patients with severe laryngomalacia.

Laryngomalacia is the top cause of pediatric laryngeal wheeze. We used computational fluid dynamics to study the inspiratory airflow dynamics in severe pediatric laryngomalacia. Computed tomography was performed on the upper airways of two infants, one with severe laryngomalacia and one with normal airway, and 3D models were reconstructed. ANSYS CFD-POST software was used to simulate airflow in these models to compare the volumetric flow rate, flow velocity, pressure, wall shear, and vortex. The volume flow rate in the laryngomalacia model was significantly reduced compared with the control model. Under inspiratory pressures, the peak flow velocity, pressure, and shear force in the control model appeared at the soft palate stenosis, while that in the laryngomalacia model appeared at the supraglottis stenosis. In both models, the maximum flow velocity and shear force increased with decreasing inspiratory pressure, while the minimum pressure decreased with decreasing inspiratory pressure. In the control model, the airflow vortex appeared anteriorly below the posterior section of the soft palate. In the laryngomalacia model, the vortex appeared anteriorly below the posterior section of the soft palate and anteriorly below the vocal folds. Our methodology provides a new mechanistic understanding of pediatric laryngomalacia.

Modifying quinolone antibiotics yields new anxiolytics.

Patients taking fluoroquinolone antibiotics such as norfloxacin exhibit a low incidence of convulsions and anxiety. These side effects probably result from antagonism of the neurotransmitter gamma-aminobutyric acid (GABA) at the brain GABA(A) receptor complex (GRC). Modification of norfloxacin yields molecules such as compound 4 that potentiate GABA action with alpha(2) subunit selectivity. Compound 4 is anxiolytic but does not cause sedation, and may represent a new class of ligands that have anxiolytic activity without sedative liability.

MicroRNA-424-5p inhibits the proliferation, migration, and invasion of nasopharyngeal carcinoma cells by decreasing AKT3 expression.

This study examined the expression and potential mechanism of microRNA (miRNA)-424-5p in nasopharyngeal carcinoma (NPC). NPC tissues were collected from 40 patients who were enrolled in the study, and skin samples were collected from 26 healthy subjects during plastic surgery as controls. We performed various in vitro assays using miR-424-5p to examine its function in primary NPC-1 cells. Bioinformatics was employed to analyze potential target genes and signaling pathways of miR-424-5p. We found that miR-424-5p expression in NPC tissues is downregulated and negatively correlated with lymph node metastasis and clinical staging. Expression of miR-424-5p in NPC cells was also downregulated, and transfection with miR-424-5p mimics inhibited proliferation, migration, and invasion of NPC-1 cells. Bioinformatics identified the AKT3 gene as a potential target of miR-424-5p and dual luciferase assays confirmed this finding. Upregulation of AKT3 expression rescued the inhibitory effect of miR-424-5p on the proliferation, migration, and invasion. Our results suggest that miR-424-5p inhibited the proliferation, migration, and invasion of NPC cells by decreasing AKT3 expression.

[Analysis of the effect of linear stapler closure pharyngeal after total laryngectomy].

Objective:To compare the effect of closure of pharyngeal cavity with linear stapler and manual suture in total laryngectomy. Method:A retrospective study was conducted on 32 patients who underwent total laryngectomy with linear stapler to close the pharyngeal from December 2014 to March 2019. Among them, 25 patients used closed technique and 7 patients used open technique. At the same time, 23 patients who underwent total laryngectomy with manual suture the pharyngeal by the same operator from January 2010 to December 2014 were collected. The clinical parameters of the two groups were compared and analyzed. Result:Compared with the control group, the closed technical group had no significant difference in terms of gender, diabetes mellitus, second surgery, T stage, and surgical method（P> 0.05）. While the age （63.60 ± 9.46） years and （54.35 ± 11.13） years , operation time （239.67 ± 88.43） min and （474.35 ± 140.16） min , oral feeding time （12.84 ± 3.65） min and （17.3 ± 9.71）min , hospitalization days after operation （ 15.48 ± 3.78） d and （20.22 ± 10.14） d, incidence of Pharygocutaneous fistula 4.0% （1/25） and 26.1% （6/23）, had significant statistical differences （P <0.05） Between two groups; Compared with the control group, the opener group had no statistically significant difference in gender, T stage, oral feeding time, hospitalization days after operation，surgical method and incidence of Pharygocutaneous fistula （P> 0.05），while there was a statistically significant difference in diabetes mellitus, second surgery, and operation time （P<0.05）. Conclusion:The linear stapler closed closure technique can reduce the incidence of Pharygocutaneous fistula, shorten the operation time and oral feeding time, and reduce the length of hospital stay.