Convolutional neural network-based vocal cord tumor classification technique for home-based self-prescreening purpose.

BACKGROUND: In this study, we proposed a deep learning technique that can simultaneously detect suspicious positions of benign vocal cord tumors in laparoscopic images and classify the types of tumors into cysts, granulomas, leukoplakia, nodules and polyps. This technique is useful for simplified home-based self-prescreening purposes to detect the generation of tumors around the vocal cord early in the benign stage. RESULTS: We implemented four convolutional neural network (CNN) models (two Mask R-CNNs, Yolo V4, and a single-shot detector) that were trained, validated and tested using 2183 laryngoscopic images. The experimental results demonstrated that among the four applied models, Yolo V4 showed the highest F1-score for all tumor types (0.7664, cyst; 0.9875, granuloma; 0.8214, leukoplakia; 0.8119, nodule; and 0.8271, polyp). The model with the lowest false-negative rate was different for each tumor type (Yolo V4 for cysts/granulomas and Mask R-CNN for leukoplakia/nodules/polyps). In addition, the embedded-operated Yolo V4 model showed an approximately equivalent F1-score (0.8529) to that of the computer-operated Yolo-4 model (0.8683). CONCLUSIONS: Based on these results, we conclude that the proposed deep-learning-based home screening techniques have the potential to aid in the early detection of tumors around the vocal cord and can improve the long-term survival of patients with vocal cord tumors.

Melatonin and verteporfin synergistically suppress the growth and stemness of head and neck squamous cell carcinoma through the regulation of mitochondrial dynamics.

The prevalence of head and neck squamous cell carcinoma (HNSCC) has continued to rise for decades. However, drug resistance to chemotherapeutics and relapse, mediated by cancer stem cells (CSCs), remains a significant impediment in clinical oncology to achieve successful treatment. Therefore, we focused on analyzing CSCs in HNSCC and demonstrated the effect of melatonin (Mel) and verteporfin (VP) on SCC-25 cells. HNSCC CSCs were enriched in the reactive oxygen species-low state and in sphere-forming cultures. Combination treatment with Mel and VP decreased HNSCC viability and increased apoptosis without causing significant damage to normal cells. Sphere-forming ability and stem cell population were reduced by co-treatment with Mel and VP, while mitochondrial ROS level was increased by the treatment. Furthermore, the expression of mitophagy markers, parkin and PINK1, was significantly decreased in the co-treated cells. Mel and VP induced mitochondrial depolarization and inhibited mitochondrial function. Parkin/TOM20 was localized near the nucleus and formed clusters of mitochondria in the cells after treatment. Moreover, Mel and VP downregulated the expression of markers involved in epithelial-mesenchymal transition and metastasis. The migration capacity of cells was significantly decreased by co-treatment with Mel and VP, accompanied by the down-regulation of MMP-2 and MMP-9 expression. Taken together, these results indicate that co-treatment with Mel and VP induces mitochondrial dysfunction, resulting in the apoptosis of CSCs. Mel and VP could thus be further investigated as potential therapies for HNSCC through their action on CSCs.

ACE2 and TMPRSS2 immunolocalization and oral manifestations of COVID-19.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into the host cells depends on the expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). We investigated the distribution of ACE2- and TMPRSS2-expressing cells in various oral tissues to identify the underlying mechanism of oral manifestations in patients with coronavirus disease 2019. SUBJECTS: We analyzed the expression patterns of ACE2 and TMPRSS2 in the oral mucosa (tongue, palate, and buccal mucosa), trigeminal ganglion, vessels, and salivary glands of 9 Sprague-Dawley rats using immunohistochemistry and immunofluorescence. RESULTS: ACE2 and TMPRSS2 were strongly expressed in the intermediate layer of the squamous epithelia of tongue papillae and buccal mucosa. ACE2- and TMPRSS2-positive cells were observed in the taste buds of the tongue. Additionally, ACE2 and TMPRSS2 were co-expressed in the ductal epithelium and acinar cells of salivary glands. Furthermore, both ACE2 and TMPRSS2 were stained in the neuronal cell body of trigeminal ganglia, but not in Schwann cells. Moreover, ACE2 and TMPRSS2 were expressed in capillaries, but not in venules/arterioles. CONCLUSIONS: SARS-CoV-2 can spread the suprabasal area of squamous epithelia of the oral mucosa, invades taste bud, trigeminal nerve, parotid gland, and microvessel, resulting in oral manifestations.

Automated laryngeal mass detection algorithm for home-based self-screening test based on convolutional neural network.

BACKGROUND: Early detection of laryngeal masses without periodic visits to hospitals is essential for improving the possibility of full recovery and the long-term survival ratio after prompt treatment, as well as reducing the risk of clinical infection. RESULTS: We first propose a convolutional neural network model for automated laryngeal mass detection based on diagnostic images captured at hospitals. Thereafter, we propose a pilot system, composed of an embedded controller, a camera module, and an LCD display, that can be utilized for a home-based self-screening test. In terms of evaluating the model's performance, the experimental results indicated a final validation loss of 0.9152 and a F1-score of 0.8371 before post-processing. Additionally, the F1-score of the original computer algorithm with respect to 100 randomly selected color-printed test images was 0.8534 after post-processing while that of the embedded pilot system was 0.7672. CONCLUSIONS: The proposed technique is expected to increase the ratio of early detection of laryngeal masses without the risk of clinical infection spread, which could help improve convenience and ensure safety of individuals, patients, and medical staff.

Risk factors affecting the treatment outcome of pediatric foreign body aspiration: significance of time factors.

PURPOSE: The aim of this study was to identify the factors affecting the prognosis of children with foreign body aspiration (FBA) after undergoing rigid bronchoscopy. METHODS: This was a case series with a chart review of 49 children under 3 years of age who underwent rigid bronchoscopy for suspected FBA at a single tertiary institution. RESULTS: The time from symptom onset to hospitalization positively correlated with the total hospitalization time (p < 0.001), postoperative hospitalization time (p = 0.006), and operation time (p = 0.013). The time from symptom onset to operation positively correlated with the total hospitalization time (p < 0.001) and operation time (p = 0.046). The time from hospitalization to operation and the operation time positively correlated with the total hospitalization time (p = 0.026, 0.044) and postoperative hospitalization time (p = 0.049, 0.003). The time from symptom onset to hospitalization positively correlated with the incidence of pneumonia (p = 0.028). CONCLUSION: Rapid hospitalization after symptom onset, rapid surgery after symptom onset, and rapid surgery after hospitalization improve the prognosis of patients with FBA. Further, a short operation time also plays a role in improving patient prognosis.

Efficacy of hemithyroidectomy in papillary thyroid carcinoma with minimal extrathyroidal extension.

PURPOSE: This study aimed to compare the oncologic outcomes of hemithyroidectomy with total thyroidectomy in clinically node-negative (cN0) papillary thyroid carcinoma (PTC) with minimal extrathyroidal extension (ETE). METHODS: Among 1826 PTC patients who underwent thyroidectomy from Jan 2001 to Dec 2014, there were 255 with unilateral cN0 PTC with minimal ETE and of equal to or less than 2 cm in size; these 255 patients were included in this study. We excluded patients who had tumor size > 2 cm, bilateral tumors, clinically positive nodes, maximal or no ETE, gross invasion of sternothyroid muscle, recurrent cancers or distant metastases. Total thyroidectomy was performed in 173 of the 255 patients, and hemithyroidectomy in 82 of them. A propensity score-matched analysis was carried out to reduce selection bias, with the following covariates: sex, age, tumor size, multiplicity and central neck dissection. RESULTS: In the baseline data of the 255 patients, female, age and tumor size were significantly higher in the total thyroidectomy group as was Stage III, whereas T and N classification did not differ in the two groups. Propensity score matching generated two matched groups of 66 patients each, in which the significant differences between the two groups seen in the baseline analysis disappeared. In the matched samples, recurrence rate (3.0% vs. 1.5%, p = 1.0) and recurrence-free survival curves did not differ between total thyroidectomy and hemithyroidectomy. CONCLUSIONS: Hemithyroidectomy can be recommended for cN0 PTC 1 cm or less with minimal ETE. Also it can be considered for cN0 PTC 11-20 mm with minimal ETE.

Development of a Novel Detachable Magnetic Nerve Stimulator for Intraoperative Neuromonitoring.

BACKGROUND: Recurrent laryngeal nerve (RLN) palsy is a serious complication of thyroid surgery. During intraoperative neuromonitoring (IONM) of the RLN in thyroid surgery, repeated shifting between surgical instruments and the nerve stimulator is cumbersome and time-consuming. Therefore, we developed a simple detachable magnetic nerve stimulator that may be connected to all metallic surgical instruments. This study aimed to investigate the feasibility and efficacy of this detachable magnetic nerve stimulator for IONM in a porcine model and humans. METHODS: Eight RLNs in four pigs and thirteen in nine patients that underwent thyroidectomy were examined. We developed a detachable nerve stimulator that combined surgical instruments with the nerve-stimulating probe. We evaluated the electromyography (EMG) amplitudes of the RLNs in pigs and patients using conventional nerve probes and surgical instruments with the novel detachable magnetic nerve stimulator attached. RESULTS: The EMG amplitudes of the eight RLNs in pigs and thirteen in patients were analyzed. The detachable magnetic nerve stimulator was feasible and safe. There was no significant difference in the EMG amplitude between instruments (P = 0.423 in animals, P = 0.446 in humans). CONCLUSIONS: The application of stimulating dissection using a detachable magnetic nerve stimulator during thyroidectomy with IONM is simple, convenient, and effective. It provides surgeons with real-time feedback of the EMG response during intermittent IONM. We propose that this novel device could be an essential guide for most surgeons, especially for less experienced head and neck surgeons.

Long-term functional voice outcomes after thyroidectomy, and effect of endotracheal intubation on voice.

PURPOSE: The aim of this study was to evaluate long-term functional voice outcomes after thyroidectomy, and the effect of endotracheal intubation on post-operative voice impairment. METHODS: We prospectively analyzed the voice outcomes of 155 serial thyroidectomy patients for up to 2 years. The control group consisted of 69 patients who underwent parotidectomy. Patients with post-operative recurrent laryngeal nerve palsy or palsy of the external branch of the superior laryngeal nerve were excluded. Self-assessment voice symptom scores (VSS) by questionnaire, and objective acoustic parameters and maximum phonation times, were evaluated pre-operatively and 1 day, 3 days, 1 week, 1 month, 3, 6, 12, 18, and 24 months after surgery. RESULTS: VSS increased from day 1 after surgery in both groups, and returned to pre-operative levels by 24 months in the thyroidectomy group and after 1 week post-operatively in the parotidectomy (control) group. The post-operative VSS of the thyroidectomy group was significantly higher than that of the control group up to 12 months post-operatively. Highest frequency decreased immediately after surgery in the thyroidectomy group, and recovered to pre-operative levels by 12 and 18 months in females and males, respectively, whereas it recovered to pre-operative levels after the first week in the control group. CONCLUSION: Impairment of voice function may persist for more than 18 months after thyroidectomy even in patients without RLN palsy. Endotracheal intubation can affect voice outcomes adversely for 1 week post-operatively.

Oncologic outcomes of robotic thyroidectomy: 5-year experience with propensity score matching.

BACKGROUND: The oncologic outcome of robotic thyroidectomy is not yet well established. The aim of this study was to evaluate the recurrence rate after robotic thyroidectomy in comparison with conventional thyroidectomy for papillary thyroid carcinoma (PTC). METHODS: We analyzed 896 patients with PTC who either underwent robotic (212 patients using a gasless unilateral axillary or an axillo-breast approach) or conventional cervical thyroidectomy (684 patients) with/without central neck dissection between October 2008 and February 2014. We excluded patients who underwent concomitant lateral neck dissection or completion thyroidectomy, and cases with T4 tumor, tumor lager than 4 cm, other types of thyroid cancer, recurrent cancer, and distant metastasis. A propensity score matching analysis was done with ten covariates including age, gender, body mass index, tumor size, multifocality, bilaterality, extrathyroidal extension, type of thyroidectomy, extent of central neck dissection, and RAI ablation to reduce selection bias. RESULTS: In baseline data, the male ratio and the mean age were lower in the robotic group. Stage, multifocality, and bilaterality were higher in the conventional group. The rate of total thyroidectomy was higher in the conventional group. The two matched groups of each 185 patients were produced and well balanced by propensity score matching. In the comparison of propensity score matched groups, operative time was longer in the robotic group (P < 0.001), and postoperative complications did not differ between the two groups, except for transient hypoparathyroidism and formation of seroma. The recurrence rate did not differ between the two groups after a mean follow-up of 43.6 months (0.5 and 1.1 % in the robotic and conventional groups, respectively, P = 0.375). CONCLUSION: The oncologic outcome of robotic thyroidectomy in 5-year experience is comparable to that of conventional thyroidectomy in selected patients with PTC.

Long-Term Voice Outcomes After Robotic Thyroidectomy.

BACKGROUND: The purpose of this study was to evaluate the long-term voice function after robotic thyroidectomy in comparison with conventional transcervical thyroidectomy. METHODS: We prospectively evaluated the voice functions of 54 patients with thyroid nodules who underwent robotic thyroidectomy by a gasless unilateral axillary or axillo-breast approach and of 70 patients who underwent conventional thyroidectomy. Subjective voice symptom score (VSS) was evaluated in questionnaires before thyroidectomy and then at 3, 6, 12, and 24 months after surgery. Objective acoustic parameters analyzed during the same period included fundamental frequency, jitter, shimmer, noise-to-harmonic ratio, highest frequency, frequency and intensity range, and maximal phonation time. RESULTS: At 3 months after surgery, VSS was better in the robotic group than in the conventional group. At 2 years after surgery, VSS had recovered to the pre-operative level in the robotic group, whereas it remained significantly worse at 2 years in the conventional group. The phonatory frequency range and highest frequency were significantly wider and higher, respectively, in the robotic group than the conventional group at 6, 12, and 24 months postoperatively.Within the robotic group, the frequency range and highest frequency recovered to pre-operative levels by 6 months, whereas in the conventional group they remained below the pre-operative levels at 2 years post-operatively. There were no differences in other acoustic parameters between the two groups of patients at any period. CONCLUSION: Up to 2 years post-operatively, robotic thyroidectomy has advantages in terms of recovery of voice symptoms and acoustic parameters over conventional thyroidectomy.

Use of oxygen reserve index during bronchoscopic balloon dilation for subglottic stenosis in a patient with left ventricular assist device implantation -a case report.

BACKGROUND: Monitoring the oxygenation status is crucial during general anesthesia to ensure patient safety. Although noninvasive pulse oximetry is commonly used to monitor percutaneous oxygen saturation (SpO2), it may not accurately reflect changes in oxygen partial pressure when the latter is excessively high or low. The oxygen reserve index (ORi) provides real-time information about the oxygen reserve status. CASE: We present a case of successful management of subglottic stenosis using balloon bronchoscopy in an infant with a left ventricular assist device implantation under ORi monitoring to predict hypoxemia during the surgical procedure. CONCLUSIONS: Utilizing ORi monitoring during anesthesia for procedures involving apnea in critically ill infants can help predict impending desaturation before a drop in SpO2 occurs, allowing anesthesiologists to effectively anticipate and manage the apnea period. Continuous ORi monitoring offers valuable insights during surgical procedures, especially in infants with compromised respiratory and cardiovascular functions.

Normative electromyography data and influencing factors in intraoperative neuromonitoring using adhesive skin electrodes during thyroid surgery.

Background: Skin electrodes have been reported to be a useful alternative recording method for intraoperative neuromonitoring (IONM) and show typical electromyography (EMG) waveforms while overcoming the shortcomings of the EMG endotracheal tube. However, the skin electrodes showed relatively lower evoked amplitudes than other recording methods. In this study, we analyzed normative EMG data using skin electrodes and factors that affect the evoked amplitude of thyroid IONM. Methods: In total, 167 patients [242 nerves at risk (NAR)] who underwent thyroidectomy under IONM with adhesive skin electrodes were analyzed. A pair of skin electrodes was attached to the lateral border of the lamina of the thyroid cartilage. Evoked EMG data, including mean amplitude and latency, obtained after stimulation of the recurrent laryngeal nerve (RLN) and vagus nerve (VN), were collected and analyzed. Results: The mean amplitudes of RLN and VN recorded via skin electrodes were 255.48±96.53 and 236.15±69.72 µV, respectively. The mean latency of the right and left RLN was 3.22±0.03 and 3.49±0.08 mS, respectively. The mean latency of the right and left VN was 5.37±0.80 and 7.57±0.10 mS, respectively. The mean amplitude was significantly lower in the obesity, male, and total thyroidectomy (TT) groups. As body mass index (BMI) and age increased, the amplitude of EMG tended to decrease significantly. Conclusions: The evoked amplitude recorded with the skin electrodes was relatively low. A larger surgical extent, obesity, male sex, and age >55 years showed significantly lower evoked amplitudes.

TGFß2-Driven Ferritin Degradation and Subsequent Ferroptosis Underlie Salivary Gland Dysfunction in Postmenopausal Conditions.

Despite the high incidence of dry mouth in postmenopausal women, its underlying mechanisms and therapeutic interventions remain underexplored. Using ovariectomized (OVX) mouse models, here this study identifies ferroptosis, an iron-dependent regulated cell death, as a central mechanism driving postmenopausal salivary gland (SG) dysfunction. In the OVX-SGs, TGFß signaling pathway is enhanced with the aberrant TGFß2 expression in SG mesenchymal cells. Intriguingly, TGFß2 treatment reduces iron-storing ferritin levels, leading to lipid peroxidation and ferroptotic death in SG epithelial organoids (SGOs). Mechanistically, TGFß2 promotes the autophagy-mediated ferritin degradation, so-called ferritinophagy. A notable overexpression of the type III TGFß receptor (TßRIII) is found in the OVX-SGs and TGFß2-treated SGOs, while the silencing of TßRIII mitigates the ferroptosis-mediated deleterious effects of TGFß2 on SGOs. Finally, administration of ferroptosis inhibitor, Liproxstatin-1 (Lip-1), improves saliva secretion in OVX mice. Present findings collectively suggest a link between TGFß signaling, ferroptosis, and SG injury, offering new therapeutic avenues for postmenopausal xerostomia.

Discovering Potential Anti-Oral Squamous Cell Carcinoma Mechanisms from Kochiae Fructus Using Network-Based Pharmacology Analysis and Experimental Validation.

The natural product Kochiae Fructus (KF) is the ripe fruit of Kochia scoparia (L.) Schrad and is renowned for its anti-inflammatory, anticancer, anti-fungal, and anti-pruritic effects. This study examined the anticancer effect of components of KF to assess its potential as an adjuvant for cancer treatment. Network-based pharmacological and docking analyses of KF found associations with oral squamous cell carcinoma. The molecular docking of oleanolic acid (OA) with LC3 and SQSTM1 had high binding scores, and hydrogen binding with amino acids of the receptors suggests that OA is involved in autophagy, rather than the apoptosis pathway. For experimental validation, we exposed SCC-15 squamous carcinoma cells derived from a human tongue lesion to KF extract (KFE), OA, and cisplatin. The KFE caused SCC-15 cell death, and induced an accumulation of the autophagy marker proteins LC3 and p62/SQSTM1. The novelty of this study lies in the discovery that the change in autophagy protein levels can be related to the regulatory death of SCC-15 cells. These findings suggest that KF is a promising candidate for future studies to provide insight into the role of autophagy in cancer cells and advance our understanding of cancer prevention and treatment.

Evaluation of Voice and Vocal Fold Vibration after Thyroidectomy Using Two-Dimensional Scanning Digital Kymography and High-Speed Videolaryngoscopy.

OBJECTIVE: Vocal dysfunction is one of the major factors that affect the health-related quality of life of patients after thyroidectomy. Conventionally, voice changes after thyroidectomy have been evaluated by videostroboscopy and acoustic analysis. Recently, two-dimensional scanning digital kymography (2D DKG) and high-speed videolaryngoscopy (HSV) have been developed and have shown usefulness in accurately evaluating vocal fold vibration. This study aimed to evaluate changes of vocal fold vibration and voice after thyroidectomy using 2D DKG and HSV. MATERIALS AND METHODS: We evaluated the voice and vocal fold movement of 24 female patients who underwent thyroidectomy in a single tertiary hospital from December 2018 to October 2019. We obtained serial 2D DKG and HSV data one day before thyroidectomy, and 1 week and 1 month after surgery. We analyzed the peak glottal area of HSV, amplitude symmetry index, phase symmetry index, and open quotient using the 2D DKG data. The parameters were calculated at three levels of the vocal fold (line 1=anterior, line 2=middle, line 3=posterior). In the same period, we performed a voice analysis evaluating voice frequency, jitter, shimmer, and noise to harmonic ratio. We also assessed maximum phonation time and subjective voice changes with voice handicap index-10 questionnaires. RESULTS: Highest frequency (F-high), frequency range (F-range), and fundamental frequency (F0) decreased at 1 week and 1 month after thyroidectomy compared with preoperative values (P = 0.003, 0.004, <0.001 and P = 0.002, 0.015, 0.001 at 1 week and 1 month, respectively). The open quotient of 2D DKG in lines 1 and 2 increased at 1 week after thyroidectomy (P = 0.011, 0.006) and recovered to preoperative levels at 1 month postoperatively (P = 0.189, 0.153). Other quantitative measures by 2D DKG and HSV did not show significant changes between the preoperative and postoperative periods. In a correlation analysis between vocal parameters from the acoustic analysis and the values obtained from 2D DKG and HSV, significant negative correlations were observed between peak glottal area and three factors (F-high, F-range, and F0) at 1 month after surgery (r = -0.589, -0.529, -0.708; P = 0.002, 0.008, <0.001, respectively). There were positive correlations between phase symmetry indexes in lines 1 and 2 and shimmer at 1 week after thyroidectomy (r = 0.489, 0.425; P = 0.015, 0.038, respectively). Phase symmetry index in line 3 showed a significant negative correlation with maximum phonation time at both 1 week and 1 month after surgery (r = -0.497, -0.439; P = 0.013, 0.032, respectively). However, there was no correlation between total score on the voice handicap index-10 questionnaires and quantitative measurements of vocal fold vibration. CONCLUSION: 2D DKG and HSV may provide important information on vocal fold vibratory patterns after thyroidectomy, and measurements made with them were correlated with maximal phonation time and acoustic parameters such as F-high, F-range, F0, shimmer.

Effect of deferoxamine and ferrostatin-1 on salivary gland dysfunction in ovariectomized rats.

The mechanism underlying xerostomia after menopause has not yet been fully elucidated. This study aimed to investigate the mechanism of xerostomia and the effect of the ferroptosis inhibitors deferoxamine (DFO) and ferrostatin-1 (FER) on salivary gland dysfunction in a postmenopausal animal model. Twenty-four female Sprague-Dawley rats were randomly divided into four groups: a SHAM group (n = 6, sham-operated rats), an OVX group (n = 6, ovariectomized rats), an FER group (n = 6, ovariectomized rats injected intraperitoneally with FER), and a DFO group (n = 6, ovariectomized rats injected intraperitoneally with DFO). GPX4 activity, iron accumulation, lipid peroxidation, inflammation, fibrosis, and salivary gland function were analyzed. Recovery of GPX4 activity and a decrease in iron accumulation and cytosolic MDA + HAE were observed in the DFO group. In addition, collagen I, collagen III, TGF-ß, IL-6, TNF-α, and TGF-ß levels were decreased in the DFO group compared to the OVX group. Recovery of GPX4 activity and the morphology of mitochondria, and reduction of cytosolic MDA + HAE were also observed in the FER group. In addition, decreased expression of inflammatory cytokines and fibrosis markers and increased expression of AQP5 were observed in both the DFO and FER groups. Postmenopausal salivary gland dysfunction is associated with ferroptosis, and DFO and FER may reverse the postmenopausal salivary gland dysfunction after menopause. DFO and FER are hence considered promising treatments for postmenopausal xerostomia.

Tensin Regulates Fundamental Biological Processes by Interacting with Integrins of Tonsil-Derived Mesenchymal Stem Cells.

Human tonsil-derived mesenchymal stem cells (TMSCs) have a superior proliferation rate and differentiation potential compared to adipose-tissue-derived MSCs (AMSCs) or bone-marrow-derived MSCs (BMSCs). TMSCs exhibit a significantly higher expression of the tensin3 gene (TNS3) than AMSCs or BMSCs. TNS is involved in cell adhesion and migration by binding to integrin beta-1 (ITG ß1) in focal adhesion. Here, we investigated the roles of four TNS isoforms, including TNS3 and their relationship with integrin in various biological processes of TMSCs. Suppressing TNS1 and TNS3 significantly decreased the cell count. The knockdown of TNS1 and TNS3 increased the gene and protein expression levels of p16, p19, and p21. TNS1 and TNS3 also have a significant effect on cell migration. Transfecting with siRNA TNS3 significantly reduced Oct4, Nanog, and Sox-2 levels. Conversely, when TNS4 was silenced, Oct4 and Sox-2 levels significantly increase. TNS1 and TNS3 promote osteogenic and adipogenic differentiation, whereas TNS4 inhibits adipogenic differentiation of TMSCs. TNS3 is involved in the control of focal adhesions by regulating integrin. Thus, TNS enables TMSCs to possess a higher proliferative capacity and differentiation potential than other MSCs. Notably, TNS3 plays a vital role in TMSC biology by regulating ITGß1 activity.

Survey of Korean head and neck surgeons and endocrinologists for the surgical extent of 1.5 and 2.5 cm papillary thyroid carcinoma.

Background: The surgical extent of 1-4 cm papillary thyroid carcinoma (PTC) is controversial. We aimed to determine the current trend in the extent of thyroidectomy and prophylactic central neck dissection (pCND) for 1.5 and 2.5 cm PTC, which are the most clinically controversial sizes. Methods: The questionnaire was sent to 342 Korean Society of Head and Neck Surgery and 160 one branch of Korean Endocrine Society members from June to July 2021 by e-mail. A questionnaire included extent of thyroidectomy [hemithyroidectomy (Hemi) vs. total thyroidectomy (TT)] and pCND according to the tumor location and degree of extrathyroidal extension (ETE) at 1.5 or 2.5 cm PTC. We compared the proportion of respondents' preference for each scenario. Results: Fifty-seven of 342 surgeons and twenty-seven of 160 endocrinologists responded to the questionnaire. At 1.5 and 2.5 cm PTC without ETE, both groups preferred Hemi, and there was no difference between the groups. When 1.5 or 2.5 cm PTC with anterior minimal ETE was suspected, the preference for Hemi by endocrinologists was significantly lower than that by surgeons (P<0.05). When anterior and posterior gross ETE were suspected, TT was preferred in both groups. When anterior gross ETE was suspected, the preference for Hemi by endocrinologists was significantly lower than that by surgeons (P<0.05). There was no difference between the groups in the posterior gross ETE. Surgeons preferred Hemi and endocrinologists preferred TT for a 1.5 cm PTC located in the isthmus. The pCND showed a similar pattern in both groups according to the size and location of the tumor and the degree of ETE. The proportion of Hemi did not differ between high-experience and low-experience endocrinologists. Also, there was no significant difference in preference for surgical extent between low-volume and high-volume surgeons. Conclusions: TT was frequently preferred in tumors with a large size or gross ETE, and pCND was frequently preferred in cases of suspected gross ETE. This study shows as the extent of thyroid surgery may differ between endocrinologists and surgeons and this could be confusing to patient and affect the patient outcomes. Therefore, multidisciplinary approach considering the extent of surgery for thyroid cancer is recommended.

ACE2 and TMPRSS2 Immunolocalization and COVID-19-Related Thyroid Disorder.

Thyroid dysfunction has been reported to be an extrapulmonary symptom of COVID-19. It is important to identify the tissue subset that expresses angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), which are essential for host infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in order to understand the viral pathogenesis of COVID-19-related thyroid dysfunction. We investigated the expression and distribution of ACE2- and TMPRSS2-expressing cells in the thyroid gland. RT-PCR and Western blotting were performed on human thyroid follicular cells (Nthy-ori3-1) and rat thyroid tissues to detect the expression levels of ACE and TMPRSS2 mRNA and proteins. We also analyzed the expression patterns of ACE2 and TMPRSS2 in 9 Sprague-Dawley rats and 15 human thyroid tissues, including 5 normal, 5 with Hashimoto's thyroiditis, and 5 with Graves' disease, by immunohistochemistry (IHC) and immunofluorescence. Both ACE2 and TMPRSS2 mRNAs and proteins were detected in the thyroid tissue. However, ACE2 and TMPRSS2 proteins were not expressed in thyroid follicular cells. In IHC, ACE2 and TMPRSS2 were not stained in the follicular cells. No cells co-expressed ACE2 and TMPRSS2. ACE2 was expressed in pericytes between follicles, and TMPRSS2 was mainly stained in the colloid inside the follicle. There was no difference in expression between the normal thyroid, Hashimoto's thyroiditis, and Graves' disease. SARS-CoV-2 does not directly invade the thyroid follicular cells. Whether SARS-CoV-2 infection of pericytes can affect COVID-19-related thyroid dysfunction warrants further study.