Targeting of FSP1 regulates iron homeostasis in drug-tolerant persister head and neck cancer cells via lipid-metabolism-driven ferroptosis.

BACKGROUND: Research has demonstrated that some tumor cells can transform into drug-tolerant persisters (DTPs), which serve as a reservoir for the recurrence of the disease. The persister state in cancer cells arises due to temporary molecular reprogramming, and exploring the genetic composition and microenvironment during the development of head and neck squamous cell carcinoma (HNSCC) can enhance our comprehension of the types of cell death that HNSCC, thus identifying potential targets for innovative therapies. This project investigated lipid-metabolism-driven ferroptosis and its role in drug resistance and DTP generation in HNSCC. METHODS: High levels of FSP1 were discovered in the tissues of patients who experienced relapse after cisplatin treatment. RNA sequencing indicated that a series of genes related to lipid metabolism were also highly expressed in tissues from these patients. Consistent results were obtained in primary DTP cells isolated from patients who experienced relapse. The Cancer Genome Atlas database confirmed this finding. This revealed that the activation of drug resistance in cancer cells is influenced by FSP1, intracellular iron homeostasis, and lipid metabolism. The regulatory roles of ferroptosis suppressor protein 1 (FSP1) in HNSCC metabolic regulation were investigated. RESULTS: We generated human oral squamous cell carcinoma DTP cells (HNSCC cell line) to cisplatin and observed higher expression of FSP1 and lipid-metabolism-related targets in vitro. The shFSP1 blockade attenuated HNSCC-DTP cell stemness and downregulated tumor invasion and the metastatic rate. We found that cisplatin induced FSP1/ACSL4 axis expression in HNSC-DTPC cells. Finally, we evaluated the HNSCC CSC-inhibitory functions of iFSP1 (a metabolic drug and ferroptosis inducer) used for neo-adjuvant chemotherapy; this was achieved by inducing ferroptosis in a patient-derived xenograft mouse model. CONCLUSIONS: The present findings elucidate the link between iron homeostasis, ferroptosis, and cancer metabolism in HNSCC-DTP generation and acquisition of chemoresistance. The findings may serve as a suitable model for cancer treatment testing and prediction of precision treatment outcomes. In conclusion, this study provides clinically oriented platforms for evaluating metabolism-modulating drugs (FSP1 inhibitors) and new drug candidates of drug resistance and ferroptotic biomarkers.

PAICS/DYRK3 Multienzyme Interactions as Coregulators of Purinosome Formation and Metabolism on Radioresistance in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a prevalent type of oral cancer. While therapeutic innovations have made strides, radioresistance persists as a significant hindrance in OSCC treatment. Despite identifying numerous targets that could potentially suppress the oncogenic attributes of OSCC, the exploration of oncogenic protein kinases for cancer therapy remains limited. Consequently, the functions of many kinase proteins in OSCC continue to be largely undetermined. In this research, we aim to disclose protein kinases that target OSCC and elaborate their roles and molecular mechanisms. Through the examination of the kinome library of radiotherapy-resistant/sensitive OSCC cell lines (HN12 and SAS), we identified a key gene, the tyrosine phosphorylation-regulated kinase 3 (DYRK3), a member of the DYRK family. We developed an in vitro cell model, composed of radiation-resistant OSCC, to scrutinize the clinical implications and contributions of DYRK3 and phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthase (PAICS) signaling in OSCC. This investigation involves bioinformatics and human tissue arrays. We seek to comprehend the role of DYRK3 and PAICS signaling in the development of OSCC and its resistance to radiotherapy. Various in vitro assays are utilized to reveal the essential molecular mechanism behind radiotherapy resistance in connection with the DYRK3 and PAICS interaction. In our study, we quantified the concentrations of DYRK3 and PAICS proteins and tracked the expression levels of key pluripotency markers, particularly PPAT. Furthermore, we extended our investigation to include an analysis of Glut-1, a gene recognized for its linkage to radioresistance in oral squamous cell carcinoma (OSCC). Furthermore, we conducted an in vivo study to affirm the impact of DYRK3 and PAICS on tumor growth and radiotherapy resistance, focusing particularly on the role of DYRK3 in the radiotherapy resistance pathway. This focus leads us to identify new therapeutic agents that can combat radiotherapy resistance by inhibiting DYRK3 (GSK-626616). Our in vitro models showed that inhibiting PAICS disrupts purinosome formation and influences the survival rate of radiation-resistant OSCC cell lines. These outcomes underscore the pivotal role of the DYRK3/PAICS axis in directing OSCC radiotherapy resistance pathways and, as a result, influencing OSCC progression or therapy resistance. Our findings also reveal a significant correlation between DYRK3 expression and the PAICS enzyme in OSCC radiotherapy resistance.

Efficacy of levocetirizine in isolated rat tracheal smooth muscle.

Histamine receptor-1 (H1) antagonists like levocetirizine are frequently used nowadays to treat rhinitis patients who experience rhinorrhea and sneezing. The trachea may be affected by the H1 antagonist when it is used to treat nasal symptoms, either orally or through inhalation. The purpose of this study was to ascertain in vitro effects of levocetirizine on isolated tracheal smooth muscle. As a parasympathetic mimetic, methacholine (10-6 M) causes contractions in tracheal smooth muscle, which is how we tested effectiveness of levocetirizine on isolated rat tracheal smooth muscle. We also tested the drug's impact on electrically induced tracheal smooth muscle contractions. The impact of menthol (either before or after) on the contraction brought on by 10-6 M methacholine was also investigated. According to the results, the addition of levocetirizine at concentrations of 10-5 M or more caused a slight relaxation in response to methacholine's 10-6 M contraction. Levocetirizine could prevent spike contraction brought on by electrical field stimulation (EFS). As the concentration rose, it alone had a neglect effect on the trachea's basal tension. Before menthol was applied, levocetirizine might have also inhibited the function of the cold receptor. According to this study, levocetirizine might potentially impede the parasympathetic function of the trachea. If levocetirizine was used prior to menthol addition, it also reduced the function of cold receptors.

Validation of Fespixon in Postoperative Scar Cosmesis Using Quantitative Digital Photography Analysis.

BACKGROUND: Unsightly scarring after surgery remains a dilemma. One of the challenges is the lack of objective scar assessment tools. OBJECTIVES: This study aimed to evaluate the efficacy of a novel medicine, Fespixon, for prevention and/or alleviation of post-skin incision scarring. A second aim was to demonstrate the practicality of our digital image analysis system to see if this could serve as a sensitive tool to assess scar improvement. METHODS: A prospective, placebo-controlled trial involving patients with postoperative transverse scars was conducted. Each patient received a topical formulation of Fespixon on the left part of the scar and placebo cream on the right. In addition to recording the subjective modified Vancouver Scar Scale and visual analog scale scores, we utilized digital photography for monthly scar analysis, with CIELAB and hue serving as the colorimetric information, and with contrast, correlation, homogeneity, and entropy providing texture information. RESULTS: Forty-six participants (mean age, 52 years) were enrolled in the trial. All the parameters of subjective assessment showed superior results for the Fespixon-treated side, with significant differences in pigmentation, vascularity, pliability, height, itchiness, and patient satisfaction (P = .043, .013, .026, .002, .039, .012, respectively). The trends in color and texture showed increased relative difference ratios, with significant differences in most of the eigenvalues towards the Fespixon-treated side, including CIELAB-L* (P = .000), hue-R,G,B (red, blue, green) values (P = .034, .001, .011), contrast (P = .000), homogeneity (P = .000), correlation (P = .011), and entropy (P = .000). CONCLUSIONS: We validated the efficacy of Fespixon for postoperative scar healing based not only on subjective assessments but also on objective quantitative analyses. The results also indicated that our digital photography quantitative analysis system is an ideal tool for quantification of scar appearance.

In Vivo Automatic and Quantitative Measurement of Adult Human Larynx and Vocal Fold Images.

INTRODUCTION: Qualitative laryngoscopy belongs to a diagnostic routine. Nevertheless, quantitative morphometric measurements of laryngeal structures remain challenging. This study aimed to introduce a special laser projection device that can facilitate computer-assisted digitalized analysis and provide important quantitative information for diagnostics and treatment planning. MATERIALS AND METHODS: The laryngeal images were captured with our device, which contained two parallel laser beams in order to provide the scaling reference. The maximum length of the vocal fold during respiration and vibration (phonation), vocal width at midpoint, total fold area, maximum cross-sectional area of the glottic space, and maximum vocal fold angle were determined and calculated. These parameters were analyzed and compared on the basis of age, sex, body height, body weight and body mass index. RESULTS: A total of 87 subjects were enrolled in this study, comprising 39 males and 48 females. The age range for all subjects was 21 to 80 years old. The maximum value of the glottic area and vocal angle showed no significant gender difference. Both the respiration and vibration vocal fold length was significantly longer in males than in females. The vocal width revealed no gender difference, but the fold area during both respiration and phonation was significantly larger in men than in women. As for the respiration-to-vibration ratio of the vocal length, there was a trend, but without statistical significance (P = 0.06), toward a higher length compression ratio in men than in women. Meanwhile, age was found to have a strong relationship with vocal width during phonation. The width of vibration vocal fold decreased with aging significantly. CONCLUSION: Our innovative module can provide reference parameters, which makes it possible to directly estimate the objective absolute values of relevant laryngeal structures. Our non-invasive approach can be used during routine laryngoscopy and the findings easily documented. In future, we can extend its clinical application to measure subtle laryngeal or hypopharyngeal changes, which are difficult to objectively quantify.

The Management in Patients With Bilateral Vocal Fold Immobility: 15 Years' Experience at a Tertiary Centre.

OBJECTIVE: In order to correct the varying vocal fold positions to meet the various clinical requirements in patients with bilateral vocal fold immobility, we present pertinent surgical methods to treat them. MATERIALS AND METHODS: From 2005 to 2020, 115 patients diagnosed with bilateral vocal fold immobility were addressed for ventilation in 89 patients and for phonation in 26 patients. In the ventilation surgery group, all the neurogenic subjects received mere suture lateralization (SL) procedures and the mechanical ones underwent arytenoid release (AR) plus SL procedures if the cricoarytenoid joint fixation (CAJF) could be confirmed before operation. In the phonation group, neurogenic subjects received nonsurgical treatment and the mechanical ones underwent AR plus arytenoid adduction (AA) procedure. The decannulation rate and respiratory comfort rate for each subgroup will be calculated and the phonatory tests were conducted. RESULTS: In the ventilation group, 55% (49/89) of subjects received related surgeries. Mere SL offered 40 successful decannulation or respiratory comfort in 42 neurogenic subjects (95.2%). The single episode rate was high as 95%. An AR plus SL procedure also obtained 100% of decannulation or respiratory comfort with a single episode of surgical procedure if the CAJF could be confirmed preoperatively. In the phonation group, 15% (4/26) of subjects received appropriate surgeries. Single AR plus AA procedures also led to 100% (4/4) of the appropriate candidates serviceable sound. CONCLUSION: SL procedure keeping intact laryngeal mucosa usually offered permanent glottis enlarging effect or decannulation with a single episode of procedure. The use of arytenoid release for CAJF has led to remarkable advances in the ultimate surgical outcomes of both the ventilation and phonation in terms of decreasing revision surgeries. LEVELS OF EVIDENCE: level 4.

Characteristic cerebral perfusion pattern in neuronal intranuclear inclusion disease.

Background: Neuronal intranuclear inclusion disease (NIID), which pathogenesis remains largely unclear, is a neurodegenerative disease caused by GGC repeat expansion in NOTCH2NLC gene. As case studies have reported dynamic cortical perfusion changes in NIID, this study aimed to explore the cerebral perfusion pattern in NIID patients. Materials and methods: A total of 38 NIID patients and 34 healthy controls (HCs) were recruited, and 2 NIID patients who had had episodic symptoms within 2 months were excluded. Data on demographic characteristics and clinical features were collected. All participants underwent three-dimensional pseudo-continuous arterial spin labeling perfusion magnetic resonance imaging (MRI) scanning. Voxel-based comparisons of cerebral blood flow (CBF) were conducted. Results: NIID patients showed decreased perfusion in the cortex but increased perfusion in the deep brain regions compared with HCs. The regions with significant hypoperfusion were distributed in the bilateral frontal, temporal, parietal, and occipital gyri, with the left frontal gyrus being the most prominent. The regions with significant hyperperfusion included the bilateral basal ganglia, midbrain, pons, para-hippocampal, and parts of the bilateral cerebellum, fusiform, lingual, rectus, orbital, and cingulum anterior gyri, which were adjacent to the midline (all FDR-corrected p <0.05). When comparing the mean CBF value of the whole brain, no significant differences were observed between NIID patients and HCs (28.81 ± 10.1 vs. 27.99 ± 5.68 ml/100 g*min, p = 0.666). Voxel-based analysis showed no significant difference in cerebral perfusion between NIID patients with and without episodic symptoms. The perfusion within the bilateral middle frontal and anterior cingulate gyri showed positive correlations with MMSE and MoCA scores using age, sex, and education as covariates (p <0.005 uncorrected). Conclusion: NIID patients exhibited characteristic cortical hypoperfusion and deep brain hyperperfusion. The perfusion in the bilateral frontal lobe and cingulate gyrus was correlated with the severity of cognitive dysfunction. Cerebral perfusion change may be involved in NIID pathophysiology and serve as a potential indicator for monitoring NIID severity and progression.

TRPM7 via calcineurin/NFAT pathway mediates metastasis and chemotherapeutic resistance in head and neck squamous cell carcinoma.

The exact mechanisms of Head and neck squamous carcinoma (HNSCC) chemoresistance and metastatic transformation remain unclear. In recent decades, members of the transient receptor potential (TRP) channel family have been proposed as potential biomarkers and/or drug targets in cancer treatment. First, in a TCGA cohort of HNSCC, TRPM7 is highly expressed in cancer tissues, especially the expression in invasive cancer tissues is statistically significant (p>0.001). In GEO and TCGA cohort, patients with high expression of TRPM7 and NFATC2 have poor overall survival rates. The expression of TRPM7 and NFATC2 showed a positive correlation. Compared to human normal oral keratinocytes (hNOK), TRPM7 is overexpressed in FaDU, SAS, and TW2.6 cell lines. Similarly, patients with HNSCC exhibited higher TRPM7 expression than non-HNSCC subjects, and this high TRPM7 expression was associated with worse 5-year overall survival. Furthermore, TRPM7 inversely correlated with E-cadherin, but positively correlated with Vimentin, NANOG, and BMI-1 mRNA levels. Consistent with this, we demonstrated the overexpression of TRPM7 in cisplatin-resistant subjects, compared to the cisplatin-sensitive counterparts. Moreover, shRNA-mediated silencing of TRPM7 significantly suppressed the migration, invasion, colony formation, and tumorsphere formation of SAS cells, with associated downregulation of Snail, c-Myc, cyclin D1, SOX2, OCT4, and NANOG proteins expression. Finally, compared with the untreated wild-type SAS cells or cisplatin-treated cells, shTRPM7 alone or in combination with cisplatin significantly inhibited tumorsphere and colony formation. These findings serving as the basis for development of novel therapeutic strategies against metastasis and chemoresistance, while providing new insights into TRPM7 biology and activity in HNSCC.

Quantitative Measurement of Adult Human Larynx post General Anesthesia with Intubation.

Introduction: Post-anaesthetic sore throat (PAST) is a well-recognized consequence of tracheal intubation; however, quantitative morphometric measurements remain challenging. This study aimed to introduce a special laser projection device that can facilitate computer-assisted, digitalized analysis and provide important information on laryngeal mucosa change, pre and post-surgery under general anesthesia with intubation. Materials and methods: The laryngeal images were captured and divided into the control group and the intubation group. Image processing techniques were used to quantify the post-extubation laryngeal variation, with its distinct color space and texture features. Meanwhile, the maximum length of the vocal fold, vocal width at the midpoint, and maximum cross-sectional area of the glottic space were determined and calculated. These parameters were analyzed and compared pre and post-surgery. Results: A total of 69 subjects were enrolled in this study, comprising 32 subjects in the healthy group and 37 subjects in the intubation group. The color space and texture analysis with contrast and correlation profiles all shows trend toward higher measures in the intubation group than in the healthy group, with statistical significance and outstanding discrimination ability, especially in the interarytenoid region. The incidence of PAST was approximately 46% (17 patients). The gender difference, type of surgery, and the fixation position of the tube were not significantly related to the PAST occurrence. All the eigenvalues showed significant differences pre and post-surgery in the interarytenoid region and a significant trend toward red and increased contrast texture profiles was revealed. Furthermore, the glottic area showed a significant decrease of 25.29%, while the vocal width showed a significant increase post extubation. Conclusion: Our equipment and processing can measure subtle laryngeal changes that would allow a clinician to diagnose postoperative laryngeal inflammation in a simpler and less invasive way. The trend toward red, the increased contrast texture and vocal width, and the reduced glottic space were all compatible with post-intubation inflammatory response, especially in the interarytenoid region. This is important to know so that one can take appropriate steps to alleviate PAST in the future.

Quantitative Measurement of Throat and Larynx After Endotracheal Intubation for Palatoplasty.

Introduction: Quantitative morphometric measurements of living human upper airway remain challenging. This study aimed to introduce a special laser projection device that can facilitate computer-assisted, digitalized analysis and provide important information on airway mucosa change, before and after endotracheal intubation for palatoplasty. Materials and Methods: The laryngeal images were captured before and after surgery. Image processing techniques were used to quantize the post-operative laryngeal variation, with its distinct color space and texture features. Meanwhile, the maximum length of the vocal fold, vocal width at the midpoint, maximum cross-sectional area of the glottic space, maximum cross-sectional area of the oropharyngeal inlet (CSAOI) and the depth of the retropalatal space were determined and calculated. These parameters were analyzed and compared before and after surgery. Results: A total of 39 subjects were enrolled in this study. The color space and texture analysis all show trends toward higher measures in post-operative images than in pre-operative images, especially in the interarytenoid region. Furthermore, the glottic area showed a significant decrease of 31.2%, while the vocal width showed a significant increase after intubation. The post-operative retropalatal depth and CSAOI were significantly deeper and larger than the baseline, reaching their peak in the 4th week after the surgery, and then slightly reduced in the 12th week. Conclusion: For the first time we present a series of changes in upper airway after surgery, by using a laser module with quantitative measurement. Our equipment and processing can measure subtle mucosal changes that would allow a clinician to diagnose post-operative airway inflammation in a simpler and less invasive way. Here additional information collected by different imaging modalities would help to solve multiple current unmet needs in post-operative airway inflammation.

Semi-Supervised Deep Learning Semantic Segmentation for 3D Volumetric Computed Tomographic Scoring of Chronic Rhinosinusitis: Clinical Correlations and Comparison with Lund-Mackay Scoring.

BACKGROUND: The traditional Lund-Mackay score (TLMs) is unable to subgrade the volume of inflammatory disease. We aimed to propose an effective modification and calculated the volume-based modified LM score (VMLMs), which should correlate more strongly with clinical symptoms than the TLMs. METHODS: Semi-supervised learning with pseudo-labels used for self-training was adopted to train our convolutional neural networks, with the algorithm including a combination of MobileNet, SENet, and ResNet. A total of 175 CT sets, with 50 participants that would undergo sinus surgery, were recruited. The Sinonasal Outcomes Test-22 (SNOT-22) was used to assess disease-specific symptoms before and after surgery. A 3D-projected view was created and VMLMs were calculated for further comparison. RESULTS: Our methods showed a significant improvement both in sinus classification and segmentation as compared to state-of-the-art networks, with an average Dice coefficient of 91.57%, an MioU of 89.43%, and a pixel accuracy of 99.75%. The sinus volume exhibited sex dimorphism. There was a significant positive correlation between volume and height, but a trend toward a negative correlation between maxillary sinus and age. Subjects who underwent surgery had significantly greater TLMs (14.9 vs. 7.38) and VMLMs (11.65 vs. 4.34) than those who did not. ROC-AUC analyses showed that the VMLMs had excellent discrimination at classifying a high probability of postoperative improvement with SNOT-22 reduction. CONCLUSIONS: Our method is suitable for obtaining detailed information, excellent sinus boundary prediction, and differentiating the target from its surrounding structure. These findings demonstrate the promise of CT-based volumetric analysis of sinus mucosal inflammation.

Quantitative laryngoscopy with computer-aided diagnostic system for laryngeal lesions.

Laryngoscopes are widely used in the clinical diagnosis of laryngeal lesions, but such diagnosis relies heavily on the physician's subjective experience. The purpose of this study was to develop a computer-aided diagnostic system for the detection of laryngeal lesions based on objective criteria. This study used the distinct features of the image contour to find the clearest image in the laryngoscopic video. First to reduce the illumination problem caused by the laryngoscope lens, which could not fix the position of the light source, this study proposed image compensation to provide the image with a consistent brightness range for better performance. Second, we also proposed a method to automatically screen clear images from laryngoscopic film. Third, we used ACM to segment automatically them based on structural features of the pharynx and larynx, using hue and geometric analysis in the vocal cords and other zones. Finally, the support vector machine was used to classify laryngeal lesions based on a decision tree. This study evaluated the performance of the proposed system by assessing the laryngeal images of 284 patients. The accuracy of the detection for vocal cord polyps, cysts, leukoplakia, tumors, and healthy vocal cords were 93.15%, 95.16%, 100%, 96.42%, and 100%, respectively. The cross-validation accuracy for the five classes were 93.1%, 94.95%, 99.4%, 96.01% and 100%, respectively, and the average test accuracy for the laryngeal lesions was 93.33%. Our results showed that it was feasible to take the hue and geometric features of the larynx as signs to identify laryngeal lesions and that they could effectively assist physicians in diagnosing laryngeal lesions.

Isoorientin inhibits epithelial-to-mesenchymal properties and cancer stem-cell-like features in oral squamous cell carcinoma by blocking Wnt/ß-catenin/STAT3 axis.

Oral squamous cell carcinoma (OSCC) is among the most prevalent cancers of the head and neck. This study revealed that isoorientin attenuates OSCC cell stemness and epithelial-mesenchymal transition potential through the inhibition of JAK/signal transducer and activator of transcription 3 (STAT3) and Wnt/ß-catenin signaling in cell lines. Our findings indicated that isoorientin is a potential inhibitor of ß-catenin/STAT3 in vitro and in vivo. We analyzed possible synergism between isoorientin and cisplatin in OSCC. A sulforhodamine B assay, colony formation assay, tumorsphere-formation assay, and Wnt reporter activity assay were used for determining cell invasion, cell migration, drug cytotoxicity, and cell viability with potential molecular mechanisms in vitro. Isoorientin reduced the expression of p-STAT3, ß-catenin, and p-GSK3 as well as downstream effectors TCF1/TCF7 and LEF1 and significantly reduced ß-catenin colocalization in the nucleus. Isoorientin markedly strengthened the cytotoxic effects of cisplatin against SAS and SCC-25. Therefore, combining isoorientin and cisplatin treatments can potentially improve the anticancer effect of cisplatin. Isoorientin inhibited the tumorigenicity and growth of OSCC through the abrogation of Wnt/ß-catenin/STAT3 signaling in vivo. Thus, isoorientin disrupted the ß-catenin signaling pathway through the inactivation of STAT3 signaling. In conclusion, targeting OSCC-SC-mediated stemness with isoorientin to eradicate OSCC-SCs may be an effective strategy for preventing relapse and metastasis of OSCC and providing long-term survival benefits.

Combined Acupuncture-Hyperbaric Oxygen-Steroids Therapy for Idiopathic Sudden Sensorineural Hearing Loss: A Retrospective Observational Study.

Objectives: Acupuncture, widely used in Chinese society, has been studied as an adjunct treatment of idiopathic sudden sensorineural hearing loss (ISSNHL). The purpose of this study is to investigate the effectiveness of combined acupuncture and hyperbaric oxygen therapy (HBOT) with conventional steroid therapy for ISSNHL. Methods: This retrospective chart review enrolled 154 patients who met the ISSNHL criteria and were categorized into three groups according to the different treatment regimens. Among these patients, 43 underwent steroid therapy only (S) group, 74 received steroid and HBOT (S-H) group, and the remaining 37 were treated with combined acupuncture-HBOT in addition to steroid therapy (S-H-A) group. The outcome was determined by comparing the differences in pure-tone thresholds and absolute hearing gains after treatment calculated at each audiometric octave frequency or grouped frequencies of audiograms. Hearing recoveries classified into three grades: complete, partial, and poor were also analyzed and compared among different treatment groups. Results: All subjects presented with initial severe hearing loss with averaged hearing thresholds >70 dB. The S-H-A group exhibited good hearing improvement outcomes at each audiometric octave frequency and grouped frequencies of audiograms, with greater hearing gain and had more favorable outcomes in hearing recovery grades compared with the S group and the S-H group. Conclusions: The results obtained in this study revealed a preliminary finding of ISSNHL patients benefiting from combined acupuncture, HBOT, and conventional steroid therapy. Acupuncture is a safe and nonpharmacologic treatment option and can be considered as an initial treatment strategy in such a clinical scenario.

Adipose-derived stem cell induced-tissue repair or wound healing is mediated by the concomitant upregulation of miR-21 and miR-29b expression and activation of the AKT signaling pathway.

BACKGROUND: Adipose-derived stem cells (ADSCs), a subpopulation of mesenchymal stem cells, are characterized by their potential to differentiate into multiple cell lineages. Due to their abundance and relative ease of procurement, ADSCs are widely used for tissue repair and regeneration. However, the molecular mechanisms of the therapeutic effect of ADSCs remain unknown. METHODS: MicroRNAs have emerged as important signaling molecules in skin wound healing, and their roles in ADSC-based therapies must be addressed. Here, we investigated the potential of ADSCs in improving cutaneous wound healing in vitro and in vivo. RESULTS: We simulated the microenvironment of the wound site by coculturing human dermal fibroblasts (HDFs) with ADSCs. We found that cocultured HDFs expressed significantly higher levels of miR-29b and miR-21 and had higher proliferation and migration rates than ADSCs cultured without HDFs. Moreover, increased expression of Collagen Type I Alpha 1 Chain (COL1A1), Collagen Type III Alpha 1 Chain (COL3A1), alpha-smooth muscle actin (α-SMA), vascular endothelial growth factor (VEGF), and Phosphoinositide 3-kinase (PI3K), p-Akt and decreased expression of Phosphatase and tensin homolog (PTEN) and matrix metalloproteinase (MMP)-1 was detected, suggesting extracellular remodeling and fibroblast activation and proliferation. We validated the in vitro results by using a rodent skin excisional wound model and implanted ADSC sheets in the wound. Compared with the controls, wounds implanted with ADSC sheets had significantly higher rates of wound-closure; increased expression of α-SMA, VEGF, PI3k, PTEN, COL1A1, and COL3A1; decreased expression of PTEN and MMP1; and upregulated levels of miR-29b and miR-21 in the skin. CONCLUSION: In summary, we evidenced that ADSCs facilitate the increase in miR-29b and miR-21 levels and promote the activation and proliferation of dermal fibroblasts and extracellular matrix (ECM) remodeling, with the associated release of VEGF. Thus, the ADSC-mediated increase in microRNAs is essential in tissue repair and has a therapeutic potential in cutaneous wound healing.

Inhibition of Bruton's tyrosine kinase as a therapeutic strategy for chemoresistant oral squamous cell carcinoma and potential suppression of cancer stemness.

Locally advanced oral squamous cell carcinoma (OSCC) requires multimodal therapy, including surgery and concurrent chemoradiotherapy (CCRT). CCRT-resistant and recurrent cancer has a poor prognosis. We investigated the effects of Bruton's tyrosine kinase (BTK) on CCRT-resistant OSCC tissues. The effect of ibrutinib, a first-in-class BTK inhibitor, was tested on stem cell-like OSCC tumorspheres. A tissue array was constructed using tissue samples from 70 patients with OSCC. Human OSCC cell lines, SAS, TW2.6 and HSC-3, were examined. Wound healing, Matrigel invasion, and tumorsphere formation assays, as well as immunofluorescence analysis and flow cytometry, were used to investigate the effects of BTK knockdown (shBTK), ibrutinib, cisplatin, and ibrutinib/cisplatin combination on OSCC cells. We demonstrated that BTK was aberrantly highly expressed in the clinical CCRT-resistant OSCC tissue array, which resulted in poor overall survival in our local Tri-Service General Hospital and freely accessible TCGA OSCC cohorts. shBTK significantly downregulated the stemness markers Nanog, CD133, T cell immunoglobulin-3 (TIM-3), and Krüppel-like factor 4 (KLF4) in SAS tumorspheres and attenuated OSCC cell migration and colony formation. Ibrutinib reduced the number of aldehyde dehydrogenase (ALDH)-rich OSCC cells and reduced tumorsphere formation, migration, and invasion in a dose-dependent manner. Compared with ibrutinib or cisplatin monotherapy, the ibrutinib/cisplatin combination significantly reduced the formation of ALDH + OSCC tumorspheres and enhanced apoptosis. These results demonstrate that ibrutinib effectively inhibits the CSCs-like phenotype of OSCC cells through dysregulation of BTK/CD133 signaling. The ibrutinib/cisplatin combination may be considered for future clinical use.

Quantitative Morphometric Measurements of the Oropharynx in Obstructive Sleep Apnea Syndrome Using a Laser Depth Measurement Module.

INTRODUCTION: Current diagnostic routines in obstructive sleep apnea syndrome (OSAS), including drug-induced sleep endoscopy (DISE), provide qualitative data. Quantitative morphometric measurements of oropharyngeal structures remain challenging. This study aims to introduce a special linear laser projection device that can facilitate computer-assisted digitalized analysis and provide important quantitative information for OSAS prediction. MATERIALS AND METHODS: We used a single-wavelength green three-linear laser to provide the scaling reference, with one at an angle of 8.5 degrees with the other two which were parallel. The oropharyngeal images were divided into two groups: the non-OSAS and OSAS group, after polysomnography. A minimum of three evaluations were carried out to determine the maximum cross-sectional area of the oropharyngeal inlet (CSAOI) and the retropalatal depth. RESULTS: A total of 132 subjects were enrolled in this study, with 76 subjects in the non-OSAS group and 56 cases in the OSAS group. In the non-OSAS group, the CSAOI was significantly larger in males than in females. There was a trend toward deeper retropalatal region in men than in women (14.25 vs 11.76 mm). Correlation analysis revealed that retropalatal depth is significantly related to body height and the CSAOI. The body weight and BMI of patients with OSAS were significantly higher than those of participants without OSAS. The retropalatal depth and CSAOI were significantly decreased in OSAS patients as compared to those without OSAS. Our new parameter, the oropharyngeal index, showed the most outstanding discrimination by ROC analysis to predict OSAS. CONCLUSION: Our innovative module can provide reference parameters, which make it possible to directly estimate the objective absolute values of relevant oropharyngeal structures. Our non-invasive approach can be used for outpatient screening, since it allows the identification of potential OSAS patients who should be referred for polysomnography, as many patients do not require DISE early in their evaluation.

Laryngopharyngeal reflux image quantization and analysis of its severity.

Laryngopharyngeal reflux (LPR) is a prevalent disease affecting a high proportion of patients seeking laryngology consultation. Diagnosis is made subjectively based on history, symptoms, and endoscopic assessment. The results depend on the examiner's interpretation of endoscopic images. There are still no consistent objective diagnostic methods. The aim of this study is to use image processing techniques to quantize the laryngeal variation caused by LPR, to judge and analyze its severity. This study proposed methods of screening sharp images automatically from laryngeal endoscopic images and using throat eigen structure for automatic region segmentation. The proposed image compensation improved the illumination problems from the use of laryngoscope lens. Fisher linear discriminant was used to find out features and classification performance while support vector machine was used as the classifier for judging LPR. Evaluation results were 97.16% accuracy, 98.11% sensitivity, and 3.77% false positive rate. To evaluate the severity, quantized data of the laryngeal variation was used. LPR images were combined with reflux symptom index score chart, and severity was graded using a neural network. The results indicated 96.08% accuracy. The experiment indicated that laryngeal variation induced by LPR could be quantized by using image processing techniques to assist in diagnosing and treating LPR.

Pharyngeal reconstruction using a U-shaped pectoralis major myocutaneous flap: an effective technique that should not be forgotten.

INTRODUCTION: Although free tissue transfer is thought the best option for head and neck reconstruction, the pectoralis major myocutaneous flap (PMMCF) remains an important alternative method. The aim of this study was to assess the use of the PMMCF with the prevertebral fascia to close a pharyngeal defect. MATERIALS AND METHODS: This was a retrospective study of 30 patients who underwent circumferential pharyngeal defect reconstruction with a U-shaped PMMCF from 2009 to 2018. The flap was primarily used to reconstruct defects after tumor extirpation. RESULTS: One patient (3.3%) died of an acute myocardial infarction within 24 h of the operation. Six cases (20.0%) developed a pharyngocutaneous fistula; one of them required debridement, while the others spontaneously healed with conservative treatment. Seven cases (23.3%) developed tracheal stomal stenosis. Twenty-four (80.0%) of these cases could eat a regular diet, while the other five cases needed tube feeding. CONCLUSION: In patients with late-stage laryngopharyngeal cancer, reconstructing circumferential pharyngeal defects with the U-shaped PMMCF is an expedient alternative to free tissue transfer.

Risk of ocular complications following radiation therapy in patients with nasopharyngeal carcinoma.

OBJECTIVE: To examine the risk of ocular complications following radiotherapy in patients with nasopharyngeal carcinoma (NPC). METHODS: We adopted 1:1 propensity score matching and identified an NPC cohort (n = 736) and a comparison cohort (n = 736) that comprised non-NPC head and neck cancer patients who received radiotherapy in the National Health Insurance Research Database from 1997 to 2010. The follow-up period was terminated upon developing ocular complications (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]360-379) or on December 31, 2010. RESULTS: After adjusting for the confounding factors of the study, the NPC cohort had a higher adjusted hazard ratio (HR) for developing ocular complications than the comparison cohort (adjusted HR = 2.786, 95% confidence interval [CI] = 1.805-4.112, P < 0.001). The NPC cohort was associated with a significantly higher risk of developing ocular complications compared with the comparison cohort within 12 and after 24 months of follow-up (P < 0.05). The most common associated ocular complications were optic nerve disorder and retinopathy. CONCLUSIONS: Patients with NPC might be at higher risk of developing ocular complications after radiotherapy than non-NPC head and neck cancer patients in Taiwan. Either further investigation or routine assessments by ophthalmological physician is recommended. LEVEL OF EVIDENCE: NA Laryngoscope, 130:1270-1277, 2020.