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.

Extracerebral choroid plexus papilloma in the pharynx with airway obstruction in a newborn: a case report.

BACKGROUND: Choroid plexus papillomas (CPPs) are rare, usually benign, neoplasms originating in the central nervous system. In this study, we present the first case of a giant airway-obstructing CPP in the pharynx of a newborn. CASE PRESENTATION: A cystic mass located in the pharynx was noted in a fetus at the 29th week of gestation. Elective cesarean section was performed at the 38th week of gestation with successful intubation and ex utero intrapartum treatment. On computed tomography, there was a huge airway-obstructing cystic mass in the choana and pharynx. Elective surgery with total excision was performed, and histological examination confirmed the diagnosis of CPP. CONCLUSION: We report the first case of an extracerebral airway-obstructing CPP in the pharynx of a newborn. Radiologic examinations are not enough for the diagnosis of CPPs, and complete excision of the tumor with histological confirmation is indispensable for accurate diagnosis and treatment.

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.

Ultra-Low-Dose Neck CT With Low-Dose Contrast Material for Preoperative Staging of Thyroid Cancer: Image Quality and Diagnostic Performance.

OBJECTIVE: Although CT has been used as a complementary diagnostic method for the preoperative diagnosis of thyroid cancer, it has the shortcomings of substantial radiation exposure and the use of contrast material (CM). The purpose of this article is to evaluate the image quality and diagnostic performance of 70-kVp thyroid CT with low volumes of CM versus conventional 120-kVp thyroid CT protocol. MATERIALS AND METHODS: Eighty patients referred for preoperative thyroid CT were randomly divided into two groups (group A: 40 patients, 70 kVp, 60 mL of CM; group B: 40 patients, 120 kVp, 100 mL of CM). Quantitative and qualitative image quality and radiation doses for the two groups were compared using the Mann-Whitney U and chi-square tests. Degrees of agreement between preoperative CT staging and pathologic results were evaluated and compared using the Wald statistic. RESULTS: Calculated signal-to-noise ratios of different anatomic structures, calculated contrast-to-noise ratios, overall image quality, subjective noise, and streak artifacts were not significantly different between the two groups (all p > 0.05), and neither were the accuracies of preoperative CT staging (all p > 0.05). The estimated effective doses were significantly lower in group A (mean [± SD], 0.52 ± 0.14 mSv in group A and 2.28 ± 0.29 mSv in group B; p < 0.001). CONCLUSION: Ultra-low-dose 70-kVp CT with a low volume of CM provides sufficient image quality for preoperative staging of thyroid cancer and substantially reduces the radiation dose compared with standard 120-kVp CT.

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.

Isolation and Localization of Mesenchymal Stem Cells in Human Palatine Tonsil by W5C5 (SUSD2).

BACKGROUND/AIMS: Although tonsil-mesenchymal stem cells (T-MSCs) have been studied as a new autologous or homologous source of MSCs, research on specific markers of MSCs and localization for purified T-MSC isolation has not yet been reported. This study investigates the expression of W5C5 (SUSD2) in tonsil stromal cells and the colony-forming ability and differentiation potential of W5C5+ cells to determine the usefulness of W5C5+ MSCs as a marker that can be used for the purification of T-MSCs. In addition, the location of W5C5+ cells expressed in the tonsil tissues is examined. METHODS: T-MSCs were isolated from the tonsillar tissues of 12 patients undergoing tonsillectomy. The colony-forming ability, surface markers, proliferation potential, and differentiation capacities of purified W5C5+ MSCs, W5C5- MSCs, and unselected T-MSCs were evaluated. The location of the W5C5+ cells in the tonsillar tissues was also investigated by immunohistochemistry. RESULTS: W5C5 was expressed in 2.5±0.4% of fresh human tonsil stromal cells. W5C5+ cells formed many colonies, but W5C5- cells did not form any colonies. The colony-forming number of W5C5+ cells (74.4 ± 9.8) was significantly higher than that of unselected tonsil stromal cells (23.6 ± 3.7). However, the differences in proliferation potential, surface marker expression, and differentiation potential between W5C5+ T-MSCs and unselected T-MSCs were not significant. W5C5+ cells were identified in the perivascular area around the blood vessels. CONCLUSION: W5C5+ T-MSCs possessed typical MSC properties with high colony-forming efficiency, and niches of W5C5+ T-MSCs were located in the perivascular area of tonsil tissues. These findings suggest that W5C5 is a useful single marker for the isolation of purified T-MSCs.

Effects of donor age, long-term passage culture, and cryopreservation on tonsil-derived mesenchymal stem cells.

OBJECTIVES: Human mesenchymal stem cells (MSCs) are efficacious in various cellular therapeutic applications and have been isolated from several tissues. Recent studies have reported that human tonsil tissue contains a new source of progenitor cells, potentially applicable for cell-based therapies. Information about the effects of donor age, long-term passage and cryopreservation are essential for clinical applications and cell-based therapies. Therefore, the authors investigated how the morphology, cell-surface markers, proliferation potential and differentiation capacity of tonsil-derived MSCs (T-MSCs) were affected by donor age, long-term passage, and cryopreservation. MATERIALS AND METHODS: T-MSCs were isolated from tonsillar tissue of 20 patients undergoing tonsillectomy. Authors evaluated the effects of donor-age, long-term passage, and cryopreservation on the morphology, surface markers, proliferation potential and differentiation capacities of T-MSCs. RESULTS: T-MSCs exhibited a fibroblast-like, spindle-shaped appearance. There were no significant morphological differences according to donor age, long-term passage or cryopreservation. T-MSCs isolated from donors of various ages were positive for markers CD90, CD44, and CD73, but negative for CD45, CD31, and HLA-DR. There were no significant differences in the expression of positive and negative surface markers as a function of donor age, long-term passage and cryopreservation. T-MSCs from different donor age groups showed similar proliferation potentials after passage 2. After long-term passage and cryopreservation, there were no significant morphological differences. Cryopreservation did not affect the proliferation potential of T-MSCs, but there was a significant decrease in the proliferation potential in long-term passage T-MSCs (passage 15). The effect of donor age, long-term passage and cryopreservation on the in vitro adipogenic, osteogenic, and chondrogenic differentiation potential of T-MSCs was not significant. CONCLUSION: The effect of donor age, long-term passage culture, and cryopreservation on T-MSC properties are negligible, except for the proliferation capacity of long-term cultured T-MSCs. Therefore, T-MSCs are considered to be promising MSCs that can be used as future alternative sources for autologous or allogenic MSCs.

Ultrasonographic findings relating to lymph node metastasis in single micropapillary thyroid cancer.

BACKGROUND: In thyroid cancer, preoperative ultrasonography (US) is performed to detect the primary tumor and lymph node metastasis (LNM), which are related to prognosis. This study examined the relationships between specific US findings and LNM in micropapillary thyroid cancer (MPTC). METHODS: Data on 220 patients with solitary MPTC who underwent total thyroidectomy and neck dissection between 2008 and 2009 were evaluated retrospectively. We classified the US findings according to the nature, shape, echogenicity, extent, margin, and calcification of the primary tumor and evaluated the correlations between these findings and those of LNM. RESULTS: Hypoechogenicity (odds ratio = 2.331, P = 0.025) and marked hypoechogenicity (OR = 4.032, P = 0.016) of MPTC were risk factors for central LNM. All of the patients with lateral cervical LNM showed hypoechogenicity or marked hypoechogenicity. Hypoechogenicity (odds ratio = 5.349, P = 0.047) and other types of calcification (odds ratio = 2.495, P = 0.010) were significant risk factors for lateral cervical LNM. CONCLUSIONS: Specific sonographic findings (hypoechogenicity or marked hypoechogenicity, and calcification) suggest LNM.

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.

Evaluation of Vertical Level Differences Between Left and Right Vocal Folds Using Artificial Intelligence System in Excised Canine Larynx.

OBJECTIVES: This study aimed to establish an artificial intelligence (AI) system to classify vertical level differences between vocal folds during vocalization and to evaluate the accuracy of the classification. METHODS: We designed models with different depths between the right and left vocal folds using an excised canine larynx. Video files for the data set were obtained using a high-speed camera system and a color complementary metal oxide semiconductor camera with global shutter. The data sets were divided into training, validation, and testing. We used 20,000 images for building the model and 8000 images for testing. To perform deep learning multiclass classification and to estimate the vertical level difference, we introduced DenseNet121-ConvLSTM. RESULTS: The model was trained several times using different numbers of epochs. We achieved the most optimal results at 100 epochs, and the batch size used during training was 16. The proposed DenseNet121-ConvLSTM model achieved classification accuracies of 99.5% and 88.0% for training and testing, respectively. After verification using an external data set, the overall accuracy, precision, recall, and f1-score were 90.8%, 91.6%, 90.9%, and 91.2%, respectively. CONCLUSIONS: The newly developed AI system may be an easy and accurate method for classifying superior and inferior vertical level differences between vocal folds. Thus, this AI system can be applied and may help in the assessment of vertical level differences in patients with unilateral vocal fold paralysis.

Isolation of mesenchymal stromal cells (MSCs) from human adenoid tissue.

BACKGROUND: Mesenchymal stromal cells (MSCs) are multipotent progenitor cells that originally derived from bone marrow. Clinical use of bone marrow-derived MSC is difficult due to morbidity and low MSC abundance and isolation efficiency. Recently, MSCs have been isolated from various adult tissues. Here we report the isolation of adenoid tissue-derived MSCs (A-MSCs) and their characteristics. METHODS: We compared the surface markers, morphologies, and differentiation and proliferation capacities of previously established tonsil-derived MSCs (T-MSCs) and bone marrow-derived MSCs (BM-MSCs) with cells isolated from adenoid tissue. The immunophenotype of A-MSCs was investigated upon interferon (IFN)-γ stimulation. RESULTS: A-MSCs, T-MSCs, and BM-MSCs showed negative CD45, CD31 HLA-DR, CD34, CD14, CD19 and positive CD 90, CD44, CD73, CD105 expression. A-MSCs were fibroblast-like, spindle-shaped non-adherent cells, similar to T-MSCs and BM-MSCs. Adipogenesis was observed in A-MSCs by the formation of lipid droplets after Oil Red O staining. Osteogenesis was observed by the formation of the matrix mineralization in Alizarin Red staining. Chondrogenesis was observed by the accumulation of sulfated glycosaminoglycan-rich matrix in collagen type II staining. These data were similar to those of T-MSCs and BM-MSCs. Expression of marker genes (i.e., adipogenesis; lipoprotein lipase, proliferator-activator receptor-gamma, osteogenesis; osteocalcin, alkaline phasphatase, chondrogenesis; aggrecan, collagen type II α1) in A-MSCs were not different from those in T-MSCs and BM-MSCs. CONCLUSIONS: A-MSCs possess the characteristics of MSCs in terms of morphology, multipotent differentiation capacity, cell surface markers, and immunogeneity. Therefore, A-MSCs fulfill the definition of MSCs and represent an alternate source of MSCs.

Nodal status of central lymph nodes as a negative prognostic factor for papillary thyroid carcinoma.

BACKGROUND: The status of metastatic lymph nodes, including the size and extracapsular spread (ECS), in papillary thyroid cancer (PTC) has not been well established. This study evaluated the correlation between the specific status of central lymph node metastases (CLNM) and negative prognostic factors. METHODS: We reviewed 243 patients who underwent total thyroidectomy and neck dissection. The CLNM slides were reviewed and the relationship between the CLNM status and risk factors was analyzed. RESULTS: CLNM were found in 111 patients. ECS (+) was related to a large tumor, high number of CLNM, and large node (P < 0.05). Tumor size and number of CLNM were related to the ECS rate (OR = 3.861 and 2.491, respectively; P < 0.01) in a multivariate analysis. Large nodes (≥ 6 mm) were related to large tumor size, extrathyroidal extension, number of CLNM, and lateral cervical lymph node metastasis (LNM). Tumor size and LNM (OR = 4.519 and 7.811, respectively; P < 0.05) were related to large nodes in a multivariate analysis. CONCLUSIONS: ECS was related to node size, tumor size, and number of CLNM. Node size was related to tumor size and LNM. Thus, specific nodal status is a possible prognostic factor for PTC.

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.

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.

Posttraumatic synostosis between the thyroid cartilage and the cervical spine causing dysphagia.

A 64-year-old man, 7 years after cervical trauma, presented with severe dysphagia of 3-month duration. Computed tomography showed an unusual synostosis between the thyroid cartilage and the cervical spine at C5-6-7 on the right side. A barium swallow study revealed no laryngeal elevation during swallowing. Surgical resection of the bony fusion was performed, and the patient's dysphagia immediately improved without any complications. We report a case of delayed synostosis between the thyroid cartilage and the cervical spine causing severe dysphagia 7 years after cervical trauma. Surgical resection of the bony fusion resulted in immediate improvement of the dysphagia.

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.

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.

Tonsil mesenchymal stem cells-derived extracellular vesicles prevent submandibular gland dysfunction in ovariectomized rats.

Dry mouth that occurs after menopause significantly reduces the quality of life of the elderly. The extracellular vesicles derived from mesenchymal stem cells are being studied for application in various pathological conditions in the field of tissue regenerative medicine. This study is to investigate the therapeutic effect on salivary gland dysfunction occurring after ovariectomy using tonsil mesenchymal stem cells (T-MSCs)-derived extracellular vesicles. The rats were divided into the following groups: sham-operated rats (SHAM), rats that underwent ovariectomy (OVX), and rats that underwent OVX surgery and were simultaneously injected with T-MSC-derived extracellular vesicles (OVX+EV). The rats were sacrificed 6 weeks after ovariectomy. Estradiol levels decreased in the OVX group compared with those in the SHAM group. Extracellular vesicles had no effect on estradiol levels or estrogen receptor ß expression. The evaluation of pro-inflammatory cytokines, TNF-α and IL-6, increased in the OVX group and decreased in the OVX+EV group. The expressions of collagen I and TGFßI increased in the OVX group but decreased in the OVX+EV group. Moreover, to examine submandibular gland function, AQP5 and α-amylase expressions were downregulated in the OVX group, but improved upon exosome injection. In conclusion, T-MSC-derived extracellular vesicles are useful for the prevented submandibular gland dysfunction that occurs after menopause.

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.