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.

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.

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.

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.

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.

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.

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.

Chlorpheniramine attenuates histamine-mediated aquaporin 5 downregulation in human nasal epithelial cells via suppression of NF-κB activation.

Background: Aquaporin 5 (AQP5) is most likely the primary water channel in the human nasal mucosa and acts as a key tight junction protein. The signaling cascades responsible for AQP5 regulation are still works in progress. Objective: This study sought to determine the effects of histamine and chlorpheniramine on AQP5 expression in human nasal epithelial cells (HNEpC) and to detect the signaling cascades responsible for these effects. Methods: HNEpC were cultured with four concentrations of histamine or chlorpheniramine in vitro. The sub-cellular distribution of AQP5 was explored using immunocytochemistry. The pharmacologic effects of histamine and chlorpheniramine on the expression of the phosphorylation of cyclic adenosine monophosphate-responsive element binding protein (p-CREB), the AQP5 and the NF-κB protein were examined using Western blotting. Results: AQP5 was found to be located in cell membrane and cytoplasm and present in every group without significant difference. Histamine inhibits the expression of AQP5 and p-CREB in HNEpC, while chlorpheniramine dose-dependently increases these protein levels with statistical significance. HNEpC treated with histamine and chlorpheniramine in turn showed the same trends as those intervened separately with these two drugs. Moreover, chlorpheniramine had the ability to reverse the inhibitory effect of histamine. Western blotting analysis revealed that after incubation with 10-4 M histamine, NF-κB protein was significantly heightened by 165% compared with the untreated control group. Again, such increase can be significantly reversed after chlorpheniramine treatment. Conclusions: The current study demonstrated that histamine inhibits CREB phosphorylation in HNEpC, which results in decreased AQP5 expression via activation of NF-κB pathway. Chlorpheniramine attenuates the inhibitory effect of histamine in p-CREB/AQP5 expression via suppression of NF-κB signal cascades. This observation could provide additional insight into the anti-inflammatory effects of H1-antihistamines that contribute to maintain airway surface liquid and mucosal defense.

The association of superior attachment of uncinate process with pneumatization of middle turbinate: a computed tomographic analysis.

The frontal sinus outflow pathway is complex and can be influenced by the configuration of the uncinate process (UP). The UP can attach superior to the lamina papyracea, skull base, and middle turbinate. The factors associated with superior attachment remain unclear. This study analyzed the relationships between different types of superior UP attachment and characteristics of the surrounding structures including the agger nasi cell, skull base, and middle turbinate. This retrospective study utilized computed tomography images of 836 sides with identifiable sinus structure from 434 Taiwanese patients. Types of superior UP attachment, height of the ethmoid cribriform plate, prevalence of agger nasi cell, and degree of pneumatization of the middle turbinate were analyzed. In the current study, neither the presence of an agger nasi cell nor height of the cribriform plate had significant relationship with superior UP attachment type. However, UP attachment type was statistically significantly associated with pneumatized middle turbinate (PMT) type (p < 0.01). The PMT group had a higher incidence of UP attachment to the middle turbinate (38%) than the non-PMT group (18%). In the extensive PMT group, the incidence of UP attachment to the middle turbinate was high to 49%. In conclusion, superior UP attachment to the middle turbinate was associated with pneumatization of the middle turbinate. The UP has a greater tendency to attach to the middle turbinate in cases with more PMT.

Effect of budesonide and azelastine on histamine signaling regulation in human nasal epithelial cells.

Both glucocorticoids and H1-antihistamines are widely used on patients with airway diseases. However, their direct effects on airway epithelial cells are not fully explored. Therefore, we use the primary culture of human nasal epithelial cells (HNEpC) to delineate in vitro mucosal responses to above two drugs. HNEpC cells were cultured with/without budesonide and azelastine. The growth rate at each group was recorded and measured as population double time (PDT). The histamine1-receptor (H1R), muscarinic1-receptor (M1R) and M3R were measured using immunocytochemistry and western blotting after 7-days treatment. Then, we used histamine and methacholine to stimulate the mucus secretion from HNEpC and observed the MUC5AC expression in culture supernatants. Concentration-dependent treatment-induced inhibition of HNEpC growth rate was observed. Cells incubated with azelastine proliferated significantly slower than that with budesonide and the combined use of those drugs led to significant PDT prolong. The immunocytochemistry showed the H1R, M1R and M3R were obviously located in the cell membrane without apparent difference after treatment. However, western blotting showed that budesonide can significantly up-regulate the H1R, M1R and M3R level while azelastine had opposite effects. Histamine and methacholine stimulated MUC5AC secretion was greater in cells treated with budesonide but was lesser in those treated with azelastine, as compared to controls. Our data suggest that both budesonide and azelastine can significantly inhibit HNEpC proliferation, and therefore, be helpful in against airway remodeling. Long-term use of budesonide might amplify histamine signaling and result in airway hyperreactivity to stimulants by enhancing H1R, M1R and M3R expression while azelastine can oppose this effect. Therefore, combined use of those two drugs in patients with chronic inflammatory airway diseases may be an ideal option.

Menthol inhibiting parasympathetic function of tracheal smooth muscle.

Menthol is used as a constituent of food and drink, tobacco and cosmetics nowadays. This cold receptor agonist has been used as a nasal inhalation solution in the daily life. The effect of menthol on nasal mucosa in vivo is well known; however, the effect of the drug on tracheal smooth muscle has been rarely explored. Therefore, during administration of the drug for nasal symptoms, it might also affect the trachea via oral intake or inhalation. We used our preparation to test the effectiveness of menthol on isolated rat tracheal smooth muscle. A 5 mm long portion of rat trachea was submersed in 30 ml Krebs solution in a muscle bath at 37ºC. Changes in tracheal contractility in response to the application of a parasympathetic mimetic agent were measured using a transducer connected to a Pentium III computer equipped with polygraph software. The following assessments of menthol were performed: (1) effect on tracheal smooth muscle resting tension; (2) effect on contraction caused by 10-6 M methacholine as a parasympathetic mimetic; (3) effect of the drug on electrically induced tracheal smooth muscle contractions. Results indicated that addition of a parasympathetic mimetic to the incubation medium caused the trachea to contract in a dose-dependent manner. Addition of menthol at doses of 10-5 M or above elicited a relaxation response to 10-6 M methacholine-induced contraction. Menthol could also inhibit electrical field stimulation (EFS) induced spike contraction. However, it alone had a minimal effect on the basal tension of trachea as the concentration increased. We concluded that the degree of drug-induced tracheal contraction or relaxation was dose-dependent. In addition, this study indicated that high concentrations of menthol might actually inhibit parasympathetic function of the trachea.

Steroids and antihistamines synergize to inhibit rat's airway smooth muscle contractility.

Both glucocorticoids and H1-antihistamines were widely used on patients with allergic rhinitis (AR) and obstructive airway diseases. However, their direct effects on airway smooth muscle were not fully explored. In this study, we tested the effectiveness of prednisolone (Kidsolone) and levocetirizine (Xyzal) on isolated rat trachea submersed in Kreb's solution in a muscle bath. Changes in tracheal contractility in response to the application of parasympathetic mimetic agents were measured. The following assessments of the drug were performed: (1) effect on tracheal smooth muscle resting tension; (2) effect on contraction caused by 10(-6) M methacholine; (3) effect of the drug on electrical field stimulation (EFS) induced tracheal smooth muscle contractions. The result revealed sole use of Kidsolone or Xyzal elicited no significant effect or only a little relaxation response on tracheal tension after methacholine treatment. The tension was 90.5 ± 7.5 and 99.5 ± 0.8 % at 10(-4) M for Xyzal and 10(-5) M for Kidsolone, respectively. However, a dramatically spasmolytic effect was observed after co-administration of Kidsolone and Xyzal and the tension dropped to 67.5 ± 13.6 %, with statistical significance (p < 0.05). As for EFS-induced contractions, Kidsolone had no direct effect but Xyzal could inhibit it, with increasing basal tension. In conclusion, using glucocorticoids alone had no spasmolytic effect but they can be synergized with antihistamines to dramatically relax the trachea smooth muscle within minutes. Therefore, for AR patients with acute asthma attack, combined use of those two drugs is recommended.

Effects of sumatriptan nasal spray (Imigran) on isolated rat's tracheal smooth muscle.

Sumatriptan (Imigran) is a potent and highly selective 5-HT1 receptor agonist often used in treating acute migraine. Intranasal sumatriptan is well absorbed and is generally effective in relieving headache. However, the effects of Imigran given intratracheally have rarely been well explored. We aimed to verify the effect of Imigran, which acts on the tracheal smooth muscle directly in vitro. We examined the effectiveness of Imigran on isolated rat tracheal smooth muscle by testing: (1) effect on tracheal smooth muscle resting tension; (2) effect on contraction caused by 10(-6) M methacholine as a parasympathetic mimetic; (3) effect of the drugs on electrically induced tracheal smooth muscle contractions. The results indicated that the addition of methacholine to the incubation medium caused the trachea to contract in a dose-dependent manner. The addition of Imigran at doses of 10(-5) M or above elicited a significant relaxation response to 10(-6) M methacholine-induced contraction. Imigran could inhibit electrical field stimulation-induced spike contraction. It also had a minimal effect on the basal tension of trachea as the concentration increased. The study indicated high concentrations of Imigran could cause bronchodilation to reduce asthma attacks not only by blocking parasympathetic tone, but also by directly antagonizing the effect of cholinergic receptors.

Management of different kinds of head and neck defects with the submental flap for reconstruction.

Head and neck surgeries often accompany with moderate-sized defects that require time-consuming reconstructions by free flaps. The submental flap is a versatile and time-effective option for reconstruction of orofacial defects providing acceptable cosmetic and functional results without requiring microsurgical techniques. A retrospective case series study of patients who underwent reconstruction with the submental flap between 2009 and 2013 was conducted. There were 36 patients (33 men and 3 women), with a mean age of 56.4 years, enrolled in this study. The primary lesion sites included oral cavity (24 patients), pharynx (8 patients), larynx (2 patients), neck (1 patient) as well as maxillary sinus (1 patient). All flaps were harvested as the myocutaneous flaps. All donor sites were closed primarily without the need of additional surgery. No complete loss of the flap was encountered and two cases developed marginal necrosis of the flap. The submental flap had a reliable pedicle and had minimal donor-site morbidity. It is an excellent flap option for patients with small- to medium-sized defects in head and neck region.

A rapid and accurate technique for the identification of the recurrent laryngeal nerve.

OBJECTIVE: We studied the anatomic relationship between the recurrent laryngeal nerve (RLN) and the third tracheal ring, which was very important for rapid identification of RLN in our hands. METHODS: This study was initially performed using 8 fresh cadavers (4 female and 4 male). The transverse nerve location from the third trachea and the depth from its anterior surface were measured. We further observed the topography of RLN in relation to the trachea in 60 patients, between November 2008 and January 2011, at the Tri-Service General Hospital and Buddhist Tzu Chi General Hospital, Taipei Branch, Taiwan, with 46 lobo-isthmectomies and 14 total thyroidectomies. The time spent in identifying the RLN was also recorded. RESULTS: Among cadaver groups, the transverse distance (width) and the vertical distance (depth) averaged 3.3 and 17.6 mm, respectively. Among the clinical cases, the width and depth averaged 4.4 and 14.6 mm, respectively. The depth measured in males was significantly deeper than that in females (22.3 vs 13.2 mm) (P < .05). The time spent in identifying the RLN after starting dissection in the RLN triangle was not statistically significantly different between the cadaver group and the clinical group (10.6 ± 5.7 seconds and 15.5 ± 17.7 seconds, respectively; P > .05). The median time was 9 and 10 seconds, respectively. There was no statistically significant side-to-side difference in terms of the time spent in searching for the RLN. CONCLUSION: Using the third ring as guidance, our inferior-superior technique offers an extra benefit in identifying the RLN safely and quickly, as compared to the conventional inferior approach.

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.

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.

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.

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.