The Protective Role of Magnoliae Flos in Preventing Ovotoxicity and Managing Ovarian Function: An In Vitro and In Vivo Study.

Magnoliae Flos (MF) is a medicinal herb widely employed in traditional medicine for relieving sinusitis, allergic rhinitis, headaches, and toothaches. Here, we investigated the potential preventive effects of MF extract (MFE) against 4-vinylcyclohexene diepoxide (VCD)-induced ovotoxicity in ovarian cells and a mouse model of premature ovarian insufficiency (POI). The cytoprotective effects of MFE were assessed using CHO-K1 or COV434 cells. In vivo, B6C3F1 female mice were intraperitoneally injected with VCD for two weeks to induce POI, while MFE was orally administered for four weeks, beginning one week before VCD administration. VCD led to a significant decline in the viabilities of CHO-K1 and COV434 cells and triggered excessive reactive oxygen species (ROS) production and apoptosis specifically in CHO-K1 cells. However, pretreatment with MFE effectively prevented VCD-induced cell death and ROS generation, while also activating the Akt signaling pathway. In vivo, MFE increased relative ovary weights, follicle numbers, and serum estradiol and anti-Müllerian hormone levels versus controls under conditions of ovary failure. Collectively, our results demonstrate that MFE has a preventive effect on VCD-induced ovotoxicity through Akt activation. These results suggest that MFE may have the potential to prevent and manage conditions such as POI and diminished ovarian reserve.

Enhancer of zeste homolog 2 (EZH2)-dependent sirtuin-3 determines sensitivity to glucose starvation in radioresistant head and neck cancer cells.

Sirtuin 3 (SIRT3) regulates mitochondrial function as a mitochondrial deacetylase during oxidative stress. However, the specific regulatory mechanism and function of SIRT3 in radioresistant cancer cells are unclear. In this study, we aim to investigate how SIRT3 determines the susceptibility to glucose deprivation and its regulation in p53-based radioresistant head and neck cancer cells. We observed mitochondrial function using two established isogenic radioresistant subclones (HN3R-A [p53 null] and HN3R-B [p53 R282W]) with intratumoral p53 heterogeneity. Cell counting analysis was performed to evaluate cell proliferation and cell death. The correlation between the regulation of SIRT3 and enhancer of zeste homolog 2 (EZH2) was confirmed by immunoblotting and chromatin immunoprecipitation assay. p53-deficient radioresistant cells (HN3R-A) expression reduced SIRT3 levels and increased sensitivity to glucose deprivation due to mitochondrial dysfunction compared to other cells. In these cells, activation of SIRT3 significantly prevented glucose deprivation-induced cell death, whereas the loss of SIRT3 increased the susceptibility to glucose deficiency. We discovered that radiation-induced EZH2 directly binds to the SIRT3 promoter and represses the expression. Conversely, inhibiting EZH2 increased the expression of SIRT3 through epigenetic changes. Our findings indicate that p53-deficient radioresistant cells with enhanced EZH2 exhibit increased sensitivity to glucose deprivation due to SIRT3 suppression. The regulation of SIRT3 by EZH2 plays a critical role in determining the cell response to glucose deficiency in radioresistant cancer cells. Therefore, EZH2-dependent SIRT3 could be used as a predictive biomarker to select treatment options for patients with radiation-resistance.

Therapeutic effects of clonazepam in patients with burning mouth syndrome and various symptoms or psychological conditions.

Burning mouth syndrome (BMS) is frequently accompanied by dysgeusia and xerostomia. Clonazepam has been widely prescribed and is effective, but it is unclear whether clonazepam also affects the symptoms that accompany BMS, or whether such symptoms affect treatment outcomes. Here, we investigated the therapeutic outcomes in BMS patients with various symptoms or comorbidities. We retrospectively reviewed 41 patients diagnosed with BMS between June 2010 and June 2021 at a single institution. Patients were instructed to take clonazepam for 6 weeks. Before the first dose, burning pain intensity was measured using a visual analog scale (VAS); the unstimulated salivary flow rate (USFR), psychologic characteristics, site(s) of pain, and any taste disturbance were evaluated. Burning pain intensity was measured again after 6 weeks. Thirty-one of the 41 patents (75.7%) exhibited a depressed mood, whereas more than 67.8% of the patients exhibited anxiety. Subjective xerostomia was reported by ten patients (24.3%). The mean salivary flow rate was 0.69 mL/min and hyposalivation (an unstimulated salivary flow rate ≤ 0.5 mL/min) was apparent in ten patients (24.3%). Dysgeusia was present in 20 patients (48.7%); a bitter taste (n = 15, 75%) was reported by the largest proportion of patients. Patients who reported a bitter taste responded best in terms of burning pain reduction after 6 weeks (n = 4, 26.6%). Overall, 32 patients (78%) reported decreased oral burning pain after clonazepam (mean VAS score changed from 6.56 to 5.34) use. Patients who reported taste disturbances exhibited a significantly greater decrease in burning pain, compared with other patients (mean VAS score changed from 6.41 to 4.58) (p = 0.02). Clonazepam significantly improved burning pain in BMS patients who had taste disturbances.

Risk factors for sialocele after parotidectomy: Does tumor size really matter?

OBJECTIVE: Sialocele that develops after parotid surgery often prolongs the treatment period and stresses both the surgeon and patient. The extent of surgery and tumor size are known to be associated with sialocele occurrence. We investigated the incidence of post-parotidectomy sialocele and the associated risk factors, with a focus on tumor size. METHODS: We retrospectively reviewed the medical records of 172 patients who underwent parotidectomy between January 2013 and May 2020 at Haeundae Paik Hospital, Inje University of Korea. We stratified patients into those with and without sialocele (fluid collection in the operative bed). We compared clinical data, patient demographics, and surgical details; we identified risk factors for sialocele development after parotid surgery. RESULTS: Seventeen patients were diagnosed with post-parotidectomy sialocele (9.88%; 17/172). Univariate logistic regression revealed that the male sex, deep lobe tumor location, and large tumor size were significantly associated with postoperative sialocele (p = 0.015, 0.009, and 0.016, respectively). We subjected these parameters to multivariate analyses; the odds ratios were 3.70, 3.58, and 2.34, respectively. Receiver operating characteristic curve analyses showed that a tumor size > 2.50 cm was the optimal cutoff in terms of predicting post-parotidectomy sialocele. CONCLUSION: Male sex, a tumor in the deep lobe, and large tumor size were strongly associated with increased risk for sialocele after parotidectomy. Tumor size > 2.50 cm serves as the cutoff identifying patients likely to experience sialocele after parotid surgery.

Mesenchymal Stem Cell-Mediated Deep Tumor Delivery of Gold Nanorod for Photothermal Therapy.

Gold nanoparticles (AuNPs) with various sizes and morphologies have been extensively investigated for effective photothermal therapy (PTT) against multiple cancer types. However, a highly dynamic and complex tumor microenvironment (TME) considerably reduces the efficacy of PTT by limiting deep tumor penetration of AuNPs. Herein, we propose a mesenchymal stem cell (MSC)-mediated deep tumor delivery of gold nanorod (AuNR) for a potent PTT. First, MSCs are treated with tetraacylated N-azidomannosamine (Ac4ManNAz) to introduce modifiable azide (N3) groups on the cell surface via metabolic glycoengineering. Then, AuNRs modified with bio-orthogonal click molecules of bicyclo[6.1.0]nonyne (AuNR@BCN) are chemically conjugated to the N3 groups on the MSC surface by copper-free click chemistry reaction, resulting in AuNR@MSCs. In cultured MSCs, the appropriate condition to incorporate the AuNR into the MSCs is optimized; in addition, the photothermal efficiency of AuNR-MSCs under light irradiation are assessed, showing efficient heat generation in vitro. In colon tumor-bearing mice, intravenously injected AuNR@MSCs efficiently accumulate within the tumor tissues by allowing deep tissue penetration owing to the tumor homing effect by natural tumor tropism of AuNR@MSCs. Upon localized light irradiation, the AuNR@MSCs significantly inhibit colon tumor growth by the enhanced photothermal effect compared to conventional AuNRs. Collectively, this study shows a promising approach of MSCs-mediated deep tumor delivery of AuNR for effective PTT.

Tumor-Specific Monomethyl Auristatin E (MMAE) Prodrug Nanoparticles for Safe and Effective Chemotherapy.

A prodrug is bioreversible medication that is specifically converted to the active drugs by enzymes overexpressed in the tumor microenvironment, which can considerably reduce the chemotherapy-induced side effects. However, prodrug strategies usually have low antitumor efficacy compared to free drugs by delayed drug release. This is because they need time to be activated by enzymatic cleavage and they also cannot be fully recovered to the active drugs. Therefore, highly potent anticancer drug should be considered to expect a sufficient antitumor efficacy. Herein, we propose tumor-specific monomethyl auristatin E (MMAE) prodrug nanoparticles for safe and effective chemotherapy. The cathepsin B-specific cleavable FRRG peptide and MMAE are chemically conjugated via one-step simple synthetic chemistry. The resulting FRRG-MMAE molecules form stable nanoparticles without any additional carrier materials by hydrophobic interaction-derived aggregations. The FRRG-MMAE nanoparticles efficiently accumulate within the tumor tissues owing to the enhanced permeability and retention (EPR) effect and inhibit the tubulin polymerization by releasing free MMAE in the cathepsin B-overexpressed tumor cells. In contrast, FRRG-MMAE nanoparticles maintain a non-toxic inactive state in the normal tissues owing to innately low cathepsin B expression, thereby reducing MMAE-related severe toxicity. Collectively, this study provides a promising approach for safe and effective chemotherapy via MMAE-based prodrug nanoparticles, which may open new avenues for advanced drug design for translational nanomedicine.

A 61-Year-Old Woman Presenting with Low Back Pain Diagnosed with IgG4-Related Disease Affecting the Thoracoabdominal Aorta and Retroperitoneum.

BACKGROUND Immunoglobulin G4-related disease (IgG4-RD) includes several immune-mediated fibro-inflammatory conditions affecting multiple organs. Increased IgG4 serum levels support the diagnosis of IgG4-RD and characteristic histopathology of fibrous infiltrates or masses containing IgG4-positive plasma cells. We present the case of a 61-year-old woman with low back pain who was diagnosed with IgG4-RD involving the thoracoabdominal aorta and retroperitoneum. CASE REPORT A 61-year-old woman who had persistent low back pain was referred to a university hospital in South Korea. Computed tomography (CT) and 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/CT (F-18-FDG-PET/CT) demonstrated diffuse circumferential infiltrates from the thoracoabdominal aorta, iliac vessels, and retroperitoneum associated with right obstructive uropathy. The serum IgG4 concentration was 418.0 mg/L (reference range: 30-2000). She underwent laparoscopic retroperitoneal biopsy and received a cystoscopic double-J ureteral stent. IgG4-positive plasma cells, lymphoplasmacytic infiltration, and fibrosis were observed on histopathological examination. She was diagnosed with IgG4-RD and treated with glucocorticoids (GCs) for 6 months. She underwent femoral-to-femoral bypass graft surgery for revascularization due to occlusion of the right iliac arteries. She experienced relapse after GC discontinuation, and GC administration was resumed. She had difficulty tapering GC use owing to persistent low back pain, which improved with combined treatment of GC and immunosuppressant. CONCLUSIONS We present a case of IgG4-RD involving the thoracoabdominal aorta and retroperitoneum based on the 2019 classification criteria. The importance of radiological studies of IgG4-RD has increased, and F-18-FDG-PET/CT, which is a functional imaging modality of the whole body, is a valuable evaluation method for diagnosis and clinical outcomes.

Transoral endoscopic thyroidectomy using a self-retaining retractor as an alternative to carbon dioxide gas insufflation: A comparative analysis of 131 cases.

Although transoral endoscopic thyroid surgery affords several advantages, the use of carbon dioxide (CO2) gas to create and maintain the working space may cause complications such as subcutaneous emphysema and a CO2 embolism. We have used a self-retaining retractor as an alternative to CO2 gas insufflation for some time; we here report its feasibility and safety. We reviewed the medical records of 131 patients who underwent transoral endoscopic thyroid lobectomy; we compared the "CO2 group" and the "retractor" group. All thyroid tumors were completely removed with negative surgical margins. No major complication occurred in the retractor group. Two major events occurred in the CO2 group: one case of permanent vocal cord palsy and one CO2 embolism. Significant subcutaneous emphysema of the neck and chest were noted in 17.7% of CO2 group patients, but in no retractor group patient. Wound infection occurred in one patient in each group but improved after appropriate management. The total operation times from incision to suture did not differ significantly between the two groups (p = 0.514). Transoral endoscopic thyroidectomy using a self-retaining retractor as an alternative to CO2 gas insufflation is feasible and safe. The superiority of transoral endoscopic thyroidectomy would be emphasized by avoiding CO2 gas insufflation, thus eliminating the risk of CO2 gas-related complications.

Anti-Inflammatory and Mineralization Effects of Bromelain on Lipopolysaccharide-Induced Inflammation of Human Dental Pulp Cells.

Background and Objectives: Bromelain is a mixture of protease obtained from pineapple fruits or stems. Even though the biological mechanism of action of bromelain has not been completely understood, it is well known that bromelain possesses anticancer, anti-inflammatory and immunomodulatory effects. This study investigated the anti-inflammatory effects of bromelain on lipopolysaccharide (LPS)-induced human dental pulp cells (hDPCs). Materials and Methods: Cell viability after bromelain treatment was measured using WST-1 assay. We exposed hDPCs to 5 µg/mL of LPS with 2.5 or 5 µg/mL of bromelain. We performed reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay to detect interleukin-1ß, interleukin-6, and interleukin-8 levels. Western blots were used to detect intercellular adhesion molecules-1 (ICAM-1) and vascular cell adhesion molecules-1 (VCAM-1) levels. Immunofluorescence staining and Western blots were used to determine bromelain's anti-inflammatory mechanism. We also performed alkaline phosphatase and Alizarin red staining to verify mineralization nodule formation. Results: Bromelain at 2.5, 5, 10, or 20 µg/mL did not affect the viability of hDPCs significantly. LPS increased interleukin-1ß, interleukin-6, interleukin-8, ICAM-1 and VCAM-1 expression in hDPCs. Bromelain significantly decreased interleukin-1ß, interleukin-6, interleukin-8, ICAM-1, and VCAM-1 levels in hDPCs, which were stimulated by LPS. Bromelain treatment significantly reduced p65 phosphorylation in the cytoplasm and the nucleus. It also significantly decreased phosphorylation levels of extracellular signal-related kinases (ERK) and p38 mitogen-activated protein kinases (p38). Bromelain also promoted ALP activity and mineralized nodule formation. Conclusions: Bromelain inhibits the expression of inflammatory cytokines in LPS-stimulated hDPCs. The inhibitory effect of bromelain on inflammatory mediators is related to decreased NF-κB and the MAPK pathway. Therefore, bromelain might have the potential to be used for regenerative endodontics, including vital pulp therapy.

Potassium-Titanyl-Phosphate (KTP) Laser Photocoagulation Combined with Resection Using an Ultrasonic Scalpel for Pharyngolaryngeal Hemangioma via a Transoral Approach: Case Report and Literature Review.

BACKGROUND Hemangiomas are relatively rare, slow-growing, benign neoplasms that can cause necrosis, ulceration, and infection leading to airway obstruction or intractable hemorrhage. Controversy persists regarding the treatment options for these tumors, which include active observation, corticosteroids, sclerotherapy, laser treatment, and surgical resection. CASE REPORT A 61-year-old man presented with a 6-month history of persistent throat clearing and foreign body sensation in the throat. He was receiving medical treatment and psychotherapy for major depressive disorder and anxiety disorder. Laryngoscopy and computed tomography revealed a large, irregular, lobulated mass covered by bluish mucosa in the hypopharynx and larynx on the right without involvement of the true vocal fold or subglottis. Orotracheal intubation was performed under general anesthesia. The hemangioma abutting the epiglottis and arytenoid was dissected by CO2 laser. The hemangioma in the pharyngoepiglottic fold and aryepiglottic fold was resected using an ultrasonic scalpel. The hemangioma in the ventricle, false vocal fold, and paraglottic space was treated by potassium-titanyl-phosphate (KTP) laser photocoagulation. Pathological examination confirmed hemangioma. There has been no recurrence during 18 months of follow-up. CONCLUSIONS The treatment of pharyngolaryngeal hemangiomas is challenging. It is important to select treatment options considering the characteristics of the treatments and the anatomical and functional relationship between the hemangioma and the surrounding structures. Single-session KTP laser photocoagulation combined with surgical resection using an ultrasonic scalpel via a transoral approach according to anatomic site could be an effective treatment for pharyngolaryngeal hemangioma.

The adipokine Retnla deficiency increases responsiveness to cardiac repair through adiponectin-rich bone marrow cells.

Resistin-like alpha (Retnla) is a member of the resistin family and known to modulate fibrosis and inflammation. Here, we investigated the role of Retnla in the cardiac injury model. Myocardial infarction (MI) was induced in wild type (WT), Retnla knockout (KO), and Retnla transgenic (TG) mice. Cardiac function was assessed by echocardiography and was significantly preserved in the KO mice, while worsened in the TG group. Angiogenesis was substantially increased in the KO mice, and cardiomyocyte apoptosis was markedly suppressed in the KO mice. By Retnla treatment, the expression of p21 and the ratio of Bax to Bcl2 were increased in cardiomyocytes, while decreased in cardiac fibroblasts. Interestingly, the numbers of cardiac macrophages and unsorted bone marrow cells (UBCs) were higher in the KO mice than in the WT mice. Besides, phosphorylated histone H3(+) cells were more frequent in bone marrow of KO mice. Moreover, adiponectin in UBCs was notably higher in the KO mice compared with WT mice. In an adoptive transfer study, UBCs were isolated from KO mice to transplant to the WT infarcted heart. Cardiac function was better in the KO-UBCs transplanted group in the WT-UBCs transplanted group. Taken together, proliferative and adiponectin-rich bone marrow niche was associated with substantial cardiac recovery by suppression of cardiac apoptosis and proliferation of cardiac fibroblast.

p53-dependent glutamine usage determines susceptibility to oxidative stress in radioresistant head and neck cancer cells.

The manner in which p53 maintains redox homeostasis and the means by which two key metabolic elements, glucose and glutamine, contribute to p53-dependent redox stability remain unclear. To elucidate the manner in which p53 deals with glucose-deprived, reactive oxygen species (ROS)-prone conditions in this regard, two isogenic cancer subclones (HN3R-A and HN3R-B) bearing distinct p53 mutations as an in vitro model of intratumoral p53 heterogeneity were identified. Following cumulative irradiation, the subclones showed a similar metabolic shift to aerobic glycolysis and increasing NADPH biogenesis for cellular defense against oxidative damage irrespective of p53 status. The radioresistant cancer cells became more sensitive to glycolysis-targeting drugs. However, in glucose-deprived and ROS-prone conditions, HN3R-B, the subclone with the original p53 increased the utilization of glutamine by GLS2, thereby maintaining redox homeostasis and ATP. Conversely, HN3R-A, the p53-deficient radioresistant subclone displayed an impairment in glutamine usage and high susceptibility to metabolic stresses as well as ROS-inducing agents despite the increased ROS scavenging system. Collectively, our findings suggest that p53 governs the alternative utilization of metabolic ingredients, such as glucose and glutamine, in ROS-prone conditions. Thus, p53 status may be an important biomarker for selecting cancer treatment strategies, including metabolic drugs and ROS-inducing agents, for recurrent cancers after radiotherapy.

Can Voice Pitch Be Preserved in Patients after Transoral Endoscopic Thyroidectomy Vestibular Approach?

INTRODUCTION: Transoral endoscopic thyroidectomy vestibular approach (TOETVA) has become increasingly popular. Several reports have emphasized the safety and efficacy of this new approach. However, there is no report on functional voice outcomes, including voice pitch change after TOETVA. METHODS: The functional voice outcomes of patients undergoing TOETVA were compared with those of patients undergoing conventional thyroidectomy. A total of 82 consecutive patients were included in the study: 44 underwent thyroid lobectomy via TOETVA (transoral group) and 38 underwent thyroid lobectomy via the classic cervical approach (open group). Thyroidectomy-related voice questionnaire (TVQ), perceptual voice analysis, fiberoptic laryngoscopic and videolaryngostroboscopic examinations, and acoustic analysis were carried out before and one month after surgery. The changes in these values after surgery and the differences between the transoral and open groups were analyzed. RESULTS: We found no significant postoperative change in voice workups in either group. The mean high pitch decreased (from 367.91 ± 120.98 to 325.80 ± 100.86 Hz, p = 0.069) in the transoral group, but statistical significance was not attained. Clinically significant changes in pitch (postoperative change in speaking fundamental frequency, ΔSFF ≥ 12) after surgery were evident in seven (15.91%) patients in the transoral group and eight (21.05%) patients in the open group without significant difference (p = 0.579). CONCLUSIONS: This is the first study to assess functional voice outcomes (including pitch) after TOETVA compared with conventional open surgery. TOETVA was associated with good voice outcomes without any significant drop in pitch.

A Case of Extranodal Rosai-Dorfman Disease Presenting as an Isolated Mass on the Base of the Tongue in a 57-Year-old Woman.

BACKGROUND Rosai-Dorfman disease (RDD), is a rare, benign, proliferative, histiocytic disorder characterized by persistent massive lymphadenopathy, which mimics malignant tumors. Diagnosis of extranodal RDD without lymphadenopathy is difficult due to its unusual clinical manifestation and lack of typical histopathologic features. Hence, it requires both a high degree of clinical suspicion and careful histopathologic examination. CASE REPORT A 57-year-old woman presented with an isolated mass on the base of the tongue (BOT) without lymphadenopathy. Laryngoscopic examination revealed a mass on the midline of the BOT. The patient underwent complete surgical excision via suspension laryngoscopy with a CO2 laser. Based on the histopathologic features, including numerous histiocytic infiltrations with emperipolesis and cytoplasmic expression of S100 and CD68 in histiocytes, the diagnosis was confirmed as extranodal RDD. No further treatment was required, and follow-up evaluation revealed no evidence of recurrence. CONCLUSIONS Because no ideal therapeutic approach is available for RDD, treatment should be tailored to the clinical manifestations. To prevent airway obstruction and recurrence, surgery is considered an appropriate option in cases of localized RDD arising on the upper respiratory tract. We report an extremely rare case of extranodal RDD without lymphadenopathy in the BOT, and provide a detailed discussion of its clinical and histopathologic features and treatment with a brief review of the relevant literature.

Coxsackievirus A6-induced Hand-Foot-and-Mouth Disease Mimicking Stevens-Johnson Syndrome in an Immunocompetent Adult.

Hand-foot-and-mouth disease, a highly contagious viral infection, occurs more common in children than in adults. However, there was a recent outbreak of Coxsackievirus A6-induced infection with an atypical presentation among the adult population. Stevens-Johnson syndrome is a severe mucocutaneous disease characterized by extensive necrosis and detachment of the epidermis, and this condition is commonly caused by medications. Herein, we describe a 30-year-old male patient taking allopurinol for the management of gout. The patient presented with numerous erythematous papules, vesicles, and patches with mucosal eruptions on the whole body, oral mucositis, and fever, and he was finally diagnosed with hand-foot-and-mouth disease.

Fluorodeoxyglucose positron emission tomography/computed tomography identifying pericardial metastasis from early-stage p16-positive oropharyngeal cancer.

Pericardial metastasis from HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) without local recurrence is extremely rare. We report about a 69-year-old man exhibiting pericardial metastasis on positron emission tomography/computed tomography (PET/CT). There are currently no reports on the use of PET/CT in patients with pericardial metastasis from p16-positive OPSCCs.

Unusual iodine-131 postablation whole-body scintigraphy patterns in patients after robot-assisted/endoscopic thyroidectomy: Case series.

Robot-assisted/endoscopic thyroidectomy causes irritation due to instruments or implantation of thyroid tissue on the anterior chest wall and lower neck. We present three patients who exhibited unexpected focal lesions on postablation Iodine-131 single-photon emission computed tomography/computed tomography without biochemical and structural diseases. Meticulous surgical techniques are important to prevent complications.

Effect of parathyroid hormone-related protein on odontogenic differentiation in human dental pulp cells.

BACKGROUND: Parathyroid hormone-related protein (PTHrP) plays an important role in many physiological processes, including bone regeneration. The function of PTHrP is similar to PTH. It promotes osteogenic differentiation in MC3T3-E1 cells. The aim of this study was to investigate whether PTHrP might have odontogenic differentiation ability in human dental pulp cells (hDPCs). METHODS: The viability of hDPCs after stimulation with PTHrP was measured. Real-time polymerase chain reaction and Western blot analysis were performed to evaluate the expression levels of odontogenic markers and activation of protein kinase B (PKB/AKT), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK). To evaluate mineralized nodule formation, alkaline phosphatase (ALP) staining and alizarin red S staining were performed. RESULTS: PTHrP promoted odontogenic differentiation as evidenced by the formation of mineralized nodules, the induction of ALP activity, and the upregulation of odontogenic markers (dentin sialophosphoprotein and dentin matrix protein-1). The phosphorylation of AKT, ERK, JNK, and p38 was increased by PTHrP. However, an AKT inhibitor (LY294002), an ERK inhibitor (U0126), a JNK inhibitor (SP600125), and a p38 inhibitor (SB203580) inhibited the increase of mineralization induced by PTHrP. CONCLUSION: The present study revealed that PTHrP could promote odontogenic differentiation and mineralization through activating the AKT, ERK, JNK, and p38 signaling pathways. These results provide novel insights into the odontogenic action of PTHrP.

Transoral endoscopic thyroid surgery using robotic scope holder: Our initial experiences.

BACKGROUND: : Transoral thyroid surgery represented by the da Vinci system is attracted attention and performed by several institutions. However, the current available da Vinci system still has some limitations to be improved for transoral thyroid surgery including high cost of equipment and expendables, larger diameter scope and instruments and no tactile sensation. It triggered us interest in more easily available robotic scope holder. Soloassist II (AktorMed GmbH, Barbing, Germany) is an active endoscope holder system which is controlled by a joystick. It has total six joints: three joints which are controlled by computer, one is controlled by manual and two act as a gimbal joint following the movement of the main body. MATERIALS AND METHODS: We tried transoral endoscopic thyroidectomy using Soloassist II (AktorMed GmbH, Barbing, Germany) in December 2017 in our hospital. RESULTS: We successfully performed four thyroid lobectomies in four patients with Soloassist II. We refined and described surgical procedures in each step using video clips. It provided an excellent vibration-free stable surgical view which enabled fatigue-free work, without shaking or tilting the horizon. The surgeon could perform transoral endoscopic thyroid surgery with only one assistant surgeon. Docking and preparation time for Soloassist was within 10 min in all four patients. The setup and dismantling could be performed parallel to the usual workflow. No complication was reported by any patient. CONCLUSIONS: : The robotic scope holder (Soloassist II) seems to be safe and feasible equipment for performing transoral endoscopic thyroid surgery. Several possible advantages could be expected with this robotic scope holder.

Myeloid Sarcoma That Infiltrated a Preexisting Sebaceous Lymphadenoma in the Parotid Gland: Diagnostic Challenges and Literature Review.

Myeloid sarcoma (MS) is a rarely encountered extramedullary localized tumor that is composed of immature myeloid cells. We reported an extremely rare case of MS with concurrent bone marrow (BM) involvement that invaded into a preexisting sebaceous lymphadenoma in the parotid gland and neck lymph nodes. Prompted by this case, we also present a literature review of MS invasion into salivary glands. A 62-year-old man was initially diagnosed with carcinoma that arose in a sebaceous lymphadenoma in the parotid gland, through a total parotidectomy with neck dissection. After an extensive histopathological review that included immunohistochemistry, a pathologic diagnosis of MS with infiltration into the sebaceous lymphadenoma with concurrent BM involvement was confirmed. MS is difficult to diagnose accurately; herein, we analyzed the clinical presentations and effectiveness of the various diagnostic methods with a review of the literature. There are 17 cases, including our case, reported in 13 studies. Of the cases in which the salivary glands were affected, 10 involved the parotid gland, six involved the submandibular gland, and one involved both. Isolated invasion of the salivary gland was found in one case of parotid gland invasion and three cases of submandibular gland invasion. In 13 cases, the salivary glands were affected by various other lesions. Although there were no incidences of isolated MS, six patients were diagnosed with secondary MS and eight patients with MS with BM involvement, including this case. The diagnosis of MS is difficult given its rarity, and a high index of suspicion and integrated radiologic and careful histopathologic evaluation are required. Most cases of MS infiltrating the salivary gland might be indicated by the possibility of BM involvement. MS with BM involvement predicts poor prognosis and the need for intensive systemic treatment.