Feasibility of facial nerve monitoring using adhesive surface electrodes during parotidectomy: a comparative study with needle electrodes.

PURPOSE: Electrophysiological monitoring of the facial nerve during parotidectomy has been reported as an adjunctive method to prevent facial nerve injury. Classically, a needle electrode is used to obtain electromyographic (EMG) signals from facial muscles during facial nerve monitoring (FNM) of parotid surgery, likewise adhesive surface electrodes. This study aimed to investigate the feasibility of performing FNM with surface electrodes during parotid surgery and to compare EMG values with needle electrodes. METHODS: Thirty patients who underwent parotidectomy under FNM using adhesive surface and needle electrodes were included. Two pairs of adhesive surface electrodes and needle electrodes were used for FNM during parotid surgery. Mean amplitudes were collected after electrical facial nerve stimulation at 1 mA after specimen removal. RESULTS: The mean amplitude of the adhesive surface electrodes was 226.50 ± 118.44 µV (orbicularis oculi muscle) and 469.6 ± 306.06 µV (orbicularis oris muscle), respectively. The mean amplitude of the needle electrodes was 449.85 ± 248.10 µV (orbicularis oculi muscle) and 654.66 ± 395.71 µV (orbicularis oris muscle), respectively. The mean amplitude of the orbicularis oris muscle was significantly greater than that of the orbicularis oculi. The amplitude values measured in the orbicularis oculi muscle showed significant differences between the needle and skin electrodes. CONCLUSIONS: Facial nerve monitoring (FNM) using adhesive surface electrodes is feasible in parotid surgery. Although the mean amplitude value of the surface electrode was relatively lower than that of the needle electrode, the surface electrode is considered a feasible and safe EMG recording device for FNM in parotid surgery.

sEVs from tonsil-derived mesenchymal stromal cells alleviate activation of hepatic stellate cells and liver fibrosis through miR-486-5p.

Mesenchymal stromal cells (MSCs) are considered as a promising therapeutic tool for liver fibrosis, a main feature of chronic liver disease. Because small extracellular vesicles (sEVs) harboring a variety of proteins and RNAs are known to have similar functions with their derived cells, MSC-derived sEVs carry out the regenerative capacities of MSCs. Human tonsil-derived MSCs (T-MSCs) are reported as a novel source of MSCs, but their effects on liver fibrosis remain unclear. In the present study, we investigated the effects of T-MSC-derived sEVs on liver fibrosis. The expression of profibrotic genes decreased in human primary hepatic stellate cells (pHSCs) co-cultured with T-MSCs. Treatment of T-MSC-sEVs inactivated human and mouse pHSCs. Administration of T-MSC-sEVs ameliorated hepatic injuries and fibrosis in chronically damaged liver induced by carbon tetrachloride (CCl4). miR-486-5p highly enriched in T-MSC-sEVs targeting the hedgehog receptor, smoothened (Smo), was upregulated, whereas Smo and Gli2, the hedgehog target gene, were downregulated in pHSCs and liver tissues treated with T-MSC-sEVs or miR-486-5p mimic, indicating that sEV-miR-486 inactivates HSCs by suppressing hedgehog signaling. Our results showed that T-MSCs attenuate HSC activation and liver fibrosis by delivering sEVs, and miR-486 in the sEVs inactivates hedgehog signaling, suggesting that T-MSCs and their sEVs are novel anti-fibrotic therapeutics for treating chronic liver disease.

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.

Effect of Echinochrome A on Submandibular Gland Dysfunction in Ovariectomized Rats.

Post-menopausal dry mouth or xerostomia is caused by reduced salivary secretion. This study aimed to investigate the efficacy of echinochrome A (Ech A) in alleviating submandibular gland dysfunctions in ovariectomized rats that mimic menopause. Female rats that were eight-weeks-old were randomly divided into SHAM-6, -12; OVX-6, -12; and ECH-6, -12 groups (consisting of 6- and 12-weeks post-sham-operated, ovariectomized, and Ech A-treated ovariectomized rats, respectively). The ECH groups had lower body weight than OVX but similar food intake and estradiol or estrogen receptor ß expression. However, the ECH groups had lower mRNA expression of sterol-regulatory element binding protein-1c (Srebp-1c), acetyl-CoA carboxylase (Acc), fatty acid synthase (Fasn), cluster of differentiation 36 (Cd36), and lipid vacuole deposition than OVX mice. Moreover, reactive oxygen species (ROS), malondialdehyde (MDA), and iron accumulation were lower in the ECH than in the OVX groups. Fibrosis markers, transforming growth factor ß (Tgf-ßI and Tgf-ßII mRNA) increased in the OVX than SHAM groups but decreased in the ECH groups. Aquaporin (Aqp-1 and Aqp-5 mRNA) and mucin expressions were downregulated in the OVX groups but improved with Ech A. In addition, Ech A prevented post-menopausal salivary gland dysfunction by inhibiting lipogenesis and ferroptosis. These findings suggest Ech A as an effective remedy for treating menopausal dry mouth.

Perfusion-Decellularized Larynx as a Natural 3D Scaffold in a Rabbit Model.

INTRODUCTION: Decellularized larynges could be used as scaffolds to regenerate the larynx. The purpose of this study was to establish a perfusion decellularization protocol to produce a 3-dimensional whole laryngeal extracellular matrix (ECM) scaffold in a rabbit model. METHODS: The larynges of 20 rabbits assigned to the study group were harvested and decellularized using a perfusion decellularization protocol, while the larynges of 10 rabbits in the control group were harvested and untreated. Macroscopic and microscopic morphological analyses, a molecular analysis, a cellular content analysis, and scanning electron microscopy were performed. RESULTS: A histological analysis showed the absence of cellular components, the presence of the ECM, and an intact cartilage structure filled with chondrocytes. The mean total DNA amounts of the native larynx, decellularized larynx, and decellularized cartilage-free larynx were 1,826.40, 434.70, and 41.40 µg/µL, respectively; those for the decellularized larynx and decellularized cartilage-free larynx were significantly lower (p < 0.001 and p < 0.001, respectively). The total amount of DNA in the decellularized sample was significantly lower compared to that in the native sample, at 57.2% in cartilage (p < 0.001), 2.4% in the thyroid gland (p < 0.001), 2.7% in muscle (p < 0.001), 1.6% in vessels (p < 0.001), and 4.8% in the vocal cords (p < 0.001). CONCLUSION: Our perfusion decellularization protocol is feasible and reproducible to produce a 3-dimensional whole laryngeal ECM scaffold in a rabbit.

The Protective Effect of Echinochrome A on Extracellular Matrix of Vocal Folds in Ovariectomized Rats.

Here, we investigated the effects of sex hormones on extracellular matrix (ECM)-related gene expression in the vocal fold lamina propria of ovariectomized (after ovary removal) rats and verified whether echinochrome A (ECH) exerts any therapeutic effects on ECM reconstitution after estrogen deficiency in ovariectomized rats. Sprague-Dawley female rats (9 weeks old) were acclimatized for a week and randomly divided into three groups (n = 15 each group) as follows: group I (sham-operated rats, SHAM), group II (ovariectomized rats, OVX), group III (ovariectomized rats treated with ECH, OVX + ECH). Rats from the OVX + ECH group were intraperitoneally injected with ECH at 10 mg/kg thrice a week after surgery for 6 weeks. And rats were sacrificed 6 weeks after ovariectomy. Estradiol levels decreased in OVX group compared with the SHAM group. ECH treatment had no effect on the levels of estradiol and expression of estrogen receptor ß (ERß). The evaluation of ECM components showed no significant changes in elastin and hyaluronic acid levels between the different groups. Collagen I and III levels were lower in OVX group than in SHAM group but increased in OVX + ECH group. The mRNA levels of matrix metalloproteinase (MMP)-1, -2, -8, and -9 were significantly higher in the OVX group than in the SHAM group, but decreased in the OVX + ECH group. Thus, changes were observed in ECM-related genes in the OVX group upon estradiol deficiency that were ameliorated by ECH administration. Thus, the vocal fold is an estradiol-sensitive target organ and ECH may have protective effects on the ECM of vocal folds in ovariectomized rats.

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.

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.

Spinal canal morphology and clinical outcomes of microsurgical bilateral decompression via a unilateral approach for lumbar spinal canal stenosis.

PURPOSE: Microsurgical bilateral decompression via a unilateral approach for lumbar spinal stenosis is a less invasive technique compared to conventional laminectomy. Although many technical reports have demonstrated acceptable overall surgical outcomes for this approach, no studies have attempted to clarify the clinical outcomes thereof in regard to anatomical variance of the spinal canal. This study was conducted to analyze the clinical outcomes of microsurgical bilateral decompression via a unilateral approach according to spinal canal morphology in degenerative lumbar spinal stenosis. METHODS: Between January 2008 and December 2009, 144 patients with single-level spinal lumbar stenosis underwent microsurgical bilateral decompression via a unilateral approach by a single surgeon. Patients were categorized into three groups according to spinal canal shape: round (n = 42), oval (n = 36), and trefoil (n = 66), and clinical parameters were assessed both before and after surgery with 2-3 years of follow-up. RESULTS: Mean visual analog scale (VAS) and Oswestry disability index (ODI) decreased after surgery, respectively, from 8.1 and 59.8 % to 2.1 and 19.1 % in the round shaped spinal canal group, from 7.2 and 47.1 % to 2.2 and 15.1 % in the oval shaped spinal canal group, and from 6.8 and 53.6 % to 3.6 and 33.3 % in the trefoil shaped spinal canal group. In all groups, VAS and ODI scores significantly improved postoperatively (p < 0.01), although less improved VAS and ODI scores were observed in the trefoil shaped spinal canal group (p < 0.01). The overall patient satisfaction rate was 66.7 %; however, statistically significant lower satisfaction rates were reported in the trefoil shaped spinal canal group (p < 0.01). CONCLUSIONS: Microsurgical bilateral decompression via a unilateral approach may be a good modality for treating round or oval shape spinal canal stenosis, but is not recommended for trefoil-shaped-stenosis. The current authors recommend performing the bilateral decompression technique in cases of trefoil-shaped-spinal canal stenosis.

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.

Development of a multi-modal learning-based lymph node metastasis prediction model for lung cancer.

PURPOSE: This study proposed a three-dimensional (3D) multi-modal learning-based model for the automated prediction and classification of lymph node metastasis in patients with non-small cell lung cancer (NSCLC) using computed tomography (CT) images and clinical information. METHODS: We utilized clinical information and CT image data from 4239 patients with NSCLC across multiple institutions. Four deep learning algorithm-based multi-modal models were constructed and evaluated for lymph node classification. To further enhance classification performance, a soft-voting ensemble technique was applied to integrate the outcomes of multiple multi-modal models. RESULTS: A comparison of the classification performance revealed that the multi-modal model, which integrated CT images and clinical information, outperformed the single-modal models. Among the four multi-modal models, the Xception model demonstrated the highest classification performance, with an area under the curve (AUC) of 0.756 for the internal test dataset and 0.736 for the external validation dataset. The ensemble model (SEResNet50_DenseNet121_Xception) exhibited even better performance, with an AUC of 0.762 for the internal test dataset and 0.751 for the external validation dataset, surpassing the multi-modal model's performance. CONCLUSIONS: Integrating CT images and clinical information improved the performance of the lymph node metastasis prediction models in patients with NSCLC. The proposed 3D multi-modal lymph node prediction model can serve as an auxiliary tool for evaluating lymph node metastasis in patients with non-pretreated NSCLC, aiding in patient screening and treatment planning.

Efficacy of Tegoprazan in Patients with Laryngopharyngeal Reflux Disease: A Preliminary Feasibility Study.

Tegoprazan is a novel, potent, and highly selective potassium-competitive acid blocker that inhibits gastric acid secretion with rapid onset of action and prolonged control of gastric acidity. We performed a preliminary feasibility study to evaluate whether tegoprazan could control symptoms more effectively than a placebo in patients with laryngopharyngeal reflux disease (LPRD). In this double-blind, randomized, placebo-controlled trial, 35 patients with LPRD were randomly assigned to two groups: tegoprazan 50 mg daily and placebo. The primary endpoint was the complete resolution rate of LPRD symptoms after 8 weeks of medication, and the secondary endpoints were the complete resolution rate of LPRD symptoms after 4 weeks of medication and changes in the reflux symptom index (RSI) and reflux finding score (RFS) from baseline at 4 and 8 weeks of medication. There was no difference in the complete symptom resolution rates at 8 weeks between the tegoprazan and placebo groups (29.4% [5/17] vs. 27.8% [5/18], p = 1.000). Moreover, there was no significant difference in the complete symptom resolution rates at 4 weeks between the two groups. Compared with the baseline, both tegoprazan and placebo significantly reduced the total RSI and RFS scores after 4 and 8 weeks of medication; however, tegoprazan was not superior to the placebo. In conclusion, tegoprazan (50 mg daily) administration improved LPRD symptoms and signs. However, tegoprazan did not show superiority over placebo. Considering the potential effectiveness of tegoprazan as an acid-suppressing therapy and the possibility of type II error due to a low number of included patients herein, prospective, large-scale, multi-center studies with a higher dose of tegoprazan for a prolonged duration are required to elucidate the efficacy of tegoprazan in patients with LPRD. (ClinicalTrials.gov: NCT05871398).

Proliferation-Related Features of the Human Mesenchymal Stem Cells Derived from Palatine Tonsils, Adipose Tissues, and Bone Marrow.

BACKGROUND: Mesenchymal stem cells (MSCs) are widely used in regenerative medicine and cell-based transplantations. However, an in-depth comparison of the different MSC origins is lacking. This study aimed to compare the expression of adipose-derived (AMSCs), bone marrow-derived (BMSCs), and tonsil-derived (TMSCs) and evaluate whether TMSCs are good alternatives for AMSCs or BMSCs. METHODS: We analyzed the expression levels of 47,000 transcripts in AMSCs (n = 4), BMSCs (n = 4), and TMSCs (n = 4) using GeneChip. Microarray data were analyzed using the LIMMA package to compare the TMSCs, AMSCs, and BMSCs. Hub genes were analyzed using STRING and Cytoscape. To ascertain the functional roles of AURKA and AURKB, small interfering RNA (siRNA) molecules specifically targeting AURKA and AURKB mRNA were synthesized and employed to induce knockdown of AURKA and AURKB in TMSC and AMSC. We analyzed the expression level of OCT4, SOX-2, and NANOG genes in TMSC and AMSCs by cell culture and real-time PCR. RESULTS: We identified commonly increased 256 and decreased 160 genes in TMSCs from the differentially expressed genes (DEGs) between the TMSCs, AMSCs, and BMSCs. In the DEG-based protein-protein interaction and gene set enrichment analysis, hub genes (AURKA, AURKB, CDC20, and BUB1) highly expressed in TMSCs were enriched for development- and progression-related oocyte meiosis, the cell cycle, and ubiquitin-mediated proteolysis. In vitro analysis demonstrated that cells with downregulated expression of AURKA and AURKB exhibited a significant reduction in proliferation compared to control cells. However, silencing of the genes did not affect the differentiation capacity in TMSCs and AMSCs. CONCLUSION: Our study compared MSCs of different origins to better understand the similarities and differences among these cell types.

Esophageal wound healing by aligned smooth muscle cell-laden nanofibrous patch.

The esophagus exhibits peristalsis via contraction of circularly and longitudinally aligned smooth muscles, and esophageal replacement is required if there is a critical-sized wound. In this study, we proposed to reconstruct esophageal tissues using cell electrospinning (CE), an advanced technique for encapsulating living cells into fibers that allows control of the direction of fiber deposition. After treatment with transforming growth factor-ß, mesenchymal stem cell-derived smooth muscle cells (SMCs) were utilized for cell electrospinning or three-dimensional bioprinting to compare the effects of aligned micropatterns on cell morphology. CE resulted in SMCs with uniaxially arranged and elongated cell morphology with upregulated expression levels of SMC-specific markers, including connexin 43, smooth muscle protein 22 alpha (SM22α), desmin, and smoothelin. When SMC-laden nanofibrous patches were transplanted into a rat esophageal defect model, the SMC patch promoted regeneration of esophageal wounds with an increased number of newly formed blood vessels and enhanced the SMC-specific markers of SM22α and vimentin. Taken together, CE with its advantages, such as guidance of highly elongated, aligned cell morphology and accelerated SMC differentiation, can be an efficient strategy to reconstruct smooth muscle tissues and treat esophageal perforation.

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.

Guideline for the Surgical Management of Locally Invasive Differentiated Thyroid Cancer From the Korean Society of Head and Neck Surgery.

The aim of this study was to develop evidence-based recommendations for determining the surgical extent in patients with locally invasive differentiated thyroid cancer (DTC). Locally invasive DTC with gross extrathyroidal extension invading surrounding anatomical structures may lead to several functional deficits and poor oncological outcomes. At present, the optimal extent of surgery in locally invasive DTC remains a matter of debate, and there are no adequate guidelines. On October 8, 2021, four experts searched the PubMed, Embase, and Cochrane Library databases; the identified papers were reviewed by 39 experts in thyroid and head and neck surgery. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence, and to develop and report recommendations. The strength of a recommendation reflects the confidence of a guideline panel that the desirable effects of an intervention outweigh any undesirable effects, across all patients for whom the recommendation is applicable. After completing the draft guidelines, Delphi questionnaires were completed by members of the Korean Society of Head and Neck Surgery. Twenty-seven evidence-based recommendations were made for several factors, including the preoperative workup; surgical extent of thyroidectomy; surgery for cancer invading the strap muscles, recurrent laryngeal nerve, laryngeal framework, trachea, or esophagus; and surgery for patients with central and lateral cervical lymph node involvement. Evidence-based guidelines were devised to help clinicians make safer and more efficient clinical decisions for the optimal surgical treatment of patients with locally invasive DTC.

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.

Investigation of attachment location of adhesive skin electrodes for intraoperative neuromonitoring in thyroid surgery: Preclinical and clinical studies.

BACKGROUND: Recently, adhesive skin electrodes have been reported to be useful for recording electromyographic signals from intrinsic laryngeal muscles for intraoperative neuromonitoring in thyroid surgery and have shown good results compared to existing recording methods. In this study, we investigated the optimal attachment location of adhesive skin electrodes for intraoperative neuromonitoring in both porcine models and human cases. METHODS: Attachment locations were divided vertically into upper, middle, and lower locations and horizontally into medial and lateral locations to determine the optimal location of placing adhesive skin electrodes preclinically in four porcine models. This study included a total of 78 patients who underwent thyroidectomy under intraoperative neuromonitoring with adhesive skin electrodes. Sixteen patients were monitored using both adhesive skin electrodes and an electromyographic endotracheal tube. Two pairs of skin electrodes were attached to the level of the thyroid cartilage lamina. Evoked electromyographic data, including data on mean amplitude and latency, obtained by stimulating the recurrent laryngeal nerve and vagus nerve, were collected. RESULTS: Lateral attachment of adhesive skin electrodes showed significantly higher evoked amplitudes than medial attachment in both animal models and human patients. In cases where skin electrodes and an electromyographic endotracheal tube were used together, the electromyographic endotracheal tube showed a significantly higher amplitude than skin electrodes, and laterally attached skin electrodes showed a significantly higher amplitude than medially attached skin electrodes. CONCLUSION: Intraoperative neuromonitoring using adhesive skin electrodes was feasible in both animal models and human patients. We suggest that it would be better to attach adhesive skin electrodes to the lateral side of the thyroid cartilage lamina. Lateral attachment closer to the cricoarytenoid joint may be better for measuring muscle movement around the cricoarytenoid joint.