Congenital anomaly of the oval window with an abnormal facial nerve course is an uncommon embryological defect, which is related to the underdevelopment of second branchial arch derivatives. Some treatments for improving hearing levels are available; these include hearing aids, vestibulotomy, neo-oval window formation, and stapes surgeries, including incudostapedotomy and malleostapedotomy. However, surgery for congenital anomalies of the oval window has rarely been described, usually in very small series of patients. We describe two cases of congenital anomalies of the oval window with aberrant facial nerve courses. One was a 40-year-old male diagnosed with unilateral congenital oval window atresia; the other was a 10-year-old male diagnosed with bilateral congenital oval window atresia. We also describe the clinical manifestations and treatment outcomes of malleostapedotomy for congenital anomalies of the oval window with aberrant facial nerve courses.
Adult ; Branchial Region ; Child ; Facial Nerve ; Hearing ; Hearing Aids ; Hearing Loss, Conductive ; Humans ; Male ; Stapes Surgery

Although intravesical instillation of Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the most successful cancer immunotherapy for superficial bladder cancer, the serious side effects are frequently arisen by using live mycobacteria. To allow less toxic and more potent immunotherapeutic agents following intravesical BCG treatment for superficial bladder cancer, noninfectious immunotherapeutic drug instead of live BCG would be highly desirable. Recently, immune-enhancing adjuvants are considered an effective vaccine immunotherapy for cancer, providing enhanced antitumor effects and boosted immunity. The BCG-cell wall skeleton (BCG-CWS), the main immune active center of BCG, is a potent candidate as a noninfectious immunotherapeutic drug instead of live BCG against bladder cancer. However, the most limited application for anticancer therapy, it is difficult to formulate a water-soluble BCG-CWS due to the aggregation of BCG-CWS in both aqueous and nonaqueous solvents. To overcome the insolubility and improve the internalization of BCG-CWS into bladder cancer cells, it should be developed the lipid nanoparticulation of BCG-CWS, resulting in improved dispensability, stability, and small size. In addition, powerful technology of delivery systems should be applied to enhance the internalization of BCG-CWS, such as encapsulated into lipid nanoparticles using novel packaging methods. Here, we describe the progress in research on effects of BCG-CWS for cancer immunotherapy, development of lipid-based solvent, and packaging method using nanoparticles with drug delivery system.
Administration, Intravesical ; Bacillus ; Cell Wall Skeleton ; Drug Delivery Systems ; Immunotherapy ; Methods ; Mycobacterium bovis ; Nanoparticles ; Product Packaging ; Skeleton ; Solvents ; Urinary Bladder Neoplasms ; Urinary Bladder

The purpose of this study was to evaluate the color stability of light cured composite resins according to the resin matrices. Three kinds of resin matrices such as Bis-GMA (Venus® Diamond; VD), Silorane (FiltekTM P90; P90), and Ormocer (Admira; Ad) were selected. Each of them were used to prepare 30 specimens. The initial CIE L*a*b* values were measured by means of a Spectrophotometer (NF999, Nippon Denshoku, Japan). For accelerated aging process, the specimens were immersed in a circulating water bath with distilled water at 60℃. Spectrophotometric analyses were made after immersion of 8, 16, 24, 41 days and the color difference (ΔE*) was calculated. The L* value increased compared with initial L* value. VD had the greatest L* value change and Ad had the smallest L* value change (p<0.05). Ad had the greatest a* value change and VD had the smallest a* value change (p<0.05). The b* value of P90 increased steadily in positive value (+)(p<0.05). ΔE* of Ad had the smallest value and that of P90 had the greatest change with time. According to this study, the value of light cured composite resins was increased with water sorption and color of those changed into greenish and yellowish. And according to the evaluation of color stability, Ad with Ormocer as resin matrices had the best color stability with time in oral environment and P90 with Silorane as resin matrices had the lowest color stability with time. And VD had the greatest initial ΔE*.
Aging ; Baths ; Bisphenol A-Glycidyl Methacrylate ; Composite Resins ; Diamond ; Immersion ; Organically Modified Ceramics ; Silorane Resins ; Water

Transarterial chemoembolization (TACE) is reportedly a useful palliative treatment in patients with unresectable or recurred hepatocellular carcinoma. Post-TACE complications are common; however, acute cholecystitis after TACE is rare. We herein report a case of a 73-year-old woman who presented with emphysematous cholecystitis and pneumobilia following TACE. Computed tomography performed for evaluation of her tumor status before TACE incidentally showed gallbladder and common bile duct stones. After TACE, she complained of severe epigastric pain with a positive Murphy's sign. Computed tomography showed emphysematous cholecystitis and pneumobilia. She was successfully treated with emergent biliary stone removal by endoscopic retrograde cholangiopancreatography.
Aged ; Carcinoma, Hepatocellular ; Chemoembolization, Therapeutic ; Cholangiopancreatography, Endoscopic Retrograde ; Cholecystitis, Acute ; Common Bile Duct ; Emphysematous Cholecystitis ; Female ; Gallbladder ; Humans ; Palliative Care

BACKGROUND/AIMS: Exhaled nitric oxide (NO) has been extensively investigated as a marker of airway inflammation in asthma, and fractional exhaled nitric oxide (FeNO) is recognized as a useful tool for its evaluation. The aim of this study was to investigate the relationships between FeNO levels and bronchodilator response (BDR), and between FeNO and mannitol-induced airway hyperresponsiveness (AHR), in patients with suspected asthma. METHODS: Clinical variables were collected from patients aged ≥ 13 years with suspected bronchial asthma and measured levels of FeNO. These levels were compared with patient values for forced expiratory volume in the first second (FEV1) and forced expiratory flow at 25 and 75% of the pulmonary volume (FEF(25-75%)) in bronchodilator response tests under control conditions, and during bronchial provocation with mannitol. Correlations and receiver operating characteristic (ROC) curves between FeNO levels and each test were assessed. RESULTS: A total of 259 patients were included in the analysis. The mean ages of the two test groups were 41.1 and 47.8 years, respectively. FeNO levels were strongly correlated with bronchodilator response (%) and with the mannitol dose producing a 15% fall in FEV1 (PD15). On the other hand, FeNO levels were only weakly correlated with FEF(25-75%). The optimal cut-off values for FeNO to predict a positive BDR and AHR were 38.5 and 29.5 parts per billion, respectively. CONCLUSIONS: This study suggests that FEV1 and FEF(25-75%) airway responses correlate with FeNO levels in patients with suspected bronchial asthma. FeNO levels may help to predict positive responses to BDR and AHR.
Asthma* ; Forced Expiratory Volume ; Hand ; Humans ; Inflammation ; Mannitol ; Nitric Oxide* ; ROC Curve

Background and Objectives: Vitamin D modulates immunity, including that of allergic diseases, and plays its roles through contact with vitamin D receptors (VDR). Recent studies have shown that patients with allergic rhinitis have low systemic serum vitamin D level. However, the expression of VDR in local tissue such as human nasal mucosa has not been investigated. Our study demonstrated that, in nasal mucosa of normal controls and patients with allergic rhinitis. Materials and Methods: Nasal mucosa were harvested from twenty-five patients who had normal nasal mucosa and twenty-five patients with allergic rhinitis. After the total RNA isolation, we performed reverse transcriptase-polymerase chain reaction, immunohistochemical staining and western blot analysis. Results: VDR were expressed in submucosal glands and the superficial layer of epithelial cell, and that inflammatory cells are expressed more highly in the nasal mucosa of patients with allergic rhinitis compared to those without. In the mucosa of patients with allergic rhinitis, VDR expression level was upregulated compared to that in normal nasal mucosa. Conclusion This findings suggest that VDR plays a role in the pathogenesis of allergic rhinitis. Additional research is needed to determine the mechanism and consequences of VDR upregulation.

BACKGROUND: Stem cell engineering is appealing consideration for regenerating damaged endothelial cells (ECs) because stem cells can differentiate into EC-like cells. In this study, we demonstrate that tonsil-derived mesenchymal stem cells (TMSCs) can differentiate into EC-like cells under optimal physiochemical microenvironments.METHODS: TMSCs were preconditioned with Dulbecco's Modified Eagle Medium (DMEM) or EC growth medium (EGM) for 4 days and then replating them on Matrigel to observe the formation of a capillary-like network under light microscope. Microarray, quantitative real time polymerase chain reaction, Western blotting and immunofluorescence analyses were used to evaluate the expression of gene and protein of EC-related markers.RESULTS: Preconditioning TMSCs in EGM for 4 days and then replating them on Matrigel induced the formation of a capillary-like network in 3 h, but TMSCs preconditioned with DMEM did not form such a network. Genome analyses confirmed that EGM preconditioning significantly affected the expression of genes related to angiogenesis, blood vessel morphogenesis and development, and vascular development. Western blot analyses revealed that EGM preconditioning with gelatin coating induced the expression of endothelial nitric oxide synthase (eNOS), a mature EC-specific marker, as well as phosphorylated Akt at serine 473, a signaling molecule related to eNOS activation. Gelatin-coating during EGM preconditioning further enhanced the stability of the capillary-like network, and also resulted in the network more closely resembled to those observed in human umbilical vein endothelial cells.CONCLUSION: This study suggests that under specific conditions, i.e., EGM preconditioning with gelatin coating for 4 days followed by Matrigel, TMSCs could be a source of generating endothelial cells for treating vascular dysfunction.
Blood Vessels ; Blotting, Western ; Eagles ; Endothelial Cells ; Fluorescent Antibody Technique ; Gelatin ; Genome ; Human Umbilical Vein Endothelial Cells ; Mesenchymal Stromal Cells ; Morphogenesis ; Nitric Oxide Synthase Type III ; Palatine Tonsil ; Real-Time Polymerase Chain Reaction ; Serine ; Stem Cells

PURPOSE: Little is known about the clinical value of peripheral blood immune profiling. Here, we aimed to identify colorectal cancer (CRC)-related peripheral blood immune cells and develop liquid biopsy-based immune profiling models for CRC diagnosis. METHODS: Peripheral blood from 131 preoperative patients with CRC and 174 healthy controls was analyzed by flow cytometry and automated hematology. CRC-related immune factors were identified by comparing the mean values of immune cell percentages and counts. Subsequently, CRC diagnostic algorithms were constructed using binary logistic regression. RESULTS: Significant differences were observed in percentages and counts of white blood cells, lymphocytes, neutrophils, regulatory T cells, and myeloid-derived suppressor cells (MDSCs) of patients and controls. The neutrophil/lymphocyte and Th1/Th2 ratios were also significantly different. Likewise, the percentages and counts of peripheral blood programed death 1, cytotoxic T lymphocyte antigen 4, B-and T-lymphocyte attenuator, and lymphocyte activation gene-3 were higher in patients with CRC. The binary logistic regression model included 12 variables, age, CD3+%, NK%, CD4+CD279+%, CD4+CD25+%, CD4+CD152+%, CD3+CD366+%, CD3+CD272+%, CD3+CD223+%, CD158b−CD314+CD3−CD56+%, Th2%, and MDSCs cells/µL, for the prediction of cancer. Results of retrospective and prospective evaluation of the area under the curve, sensitivity, and specificity were 0.980 and 0.940, 91.53% and 85.80%, and 93.50% and 86.20%, respectively. CONCLUSION: Peripheral blood immune profiling may be valuable in evaluating the immunity of CRC patients. Our liquid biopsy-based immune diagnostic method and its algorithms may serve as a novel tool for CRC diagnosis. Future largescale studies are needed for better characterization of its diagnostic value and potential for clinical application.
Blood Cells ; Colorectal Neoplasms* ; CTLA-4 Antigen ; Diagnosis ; Early Detection of Cancer ; Flow Cytometry ; Hematology ; Humans ; Immunologic Factors ; Leukocytes ; Logistic Models ; Lymphocyte Activation ; Lymphocytes ; Methods ; Neutrophils ; Prospective Studies ; Retrospective Studies ; Sensitivity and Specificity ; T-Lymphocytes ; T-Lymphocytes, Regulatory

BACKGROUND: Beating cardiomyocyte regeneration therapies have revealed as alternative therapeutics for heart transplantation. Nonetheless, the importance of nitric oxide (NO) in cardiomyocyte regeneration has been widely suggested, little has been reported concerning endogenous NO during cardiomyocyte differentiation. METHODS: Here, we used P19CL6 cells and a Myocardiac infarction (MI) model to confirm NO-induced protein modification and its role in cardiac beating. Two tyrosine (Tyr) residues of b2-tubulin (Y106 and Y340) underwent nitrosylation (Tyr-NO) by endogenously generated NO during cardiomyocyte differentiation from pre-cardiomyocyte-like P19CL6 cells. RESULTS: Tyr-NO-b2-tubulin mediated the interaction with Stathmin, which promotes microtubule disassembly, and was prominently observed in spontaneously beating cell clusters and mouse embryonic heart (E11.5d). In myocardial infarction mice, Tyr-NO-b2-tubulin in transplanted cells was closely related with cardiac troponin-T expression with their functional recovery, reduced infarct size and thickened left ventricular wall. CONCLUSION This is the first discovery of a new target molecule of NO, b2-tubulin, that can promote normal cardiac beating and cardiomyocyte regeneration. Taken together, we suggest therapeutic potential of Tyr-NO-b2-tubulin, for ischemic cardiomyocyte, which can reduce unexpected side effect of stem cell transplantation, arrhythmogenesis.

Background: Remdesivir is widely used for the treatment of coronavirus disease 2019 (COVID-19), but controversies regarding its efficacy still remain. Methods: A retrospective cohort study was conducted to evaluate the effect of remdesivir on clinical and virologic outcomes of severe COVID-19 patients from June to July 2020. Primary clinical endpoints included clinical recovery, additional mechanical ventilator (MV) support, and duration of oxygen or MV support. Viral load reduction by hospital day (HD) 15 was evaluated by calculating changes in cycle threshold (Ct) values. Results: A total of 86 severe COVID-19 patients were evaluated including 48 remdesivirtreated patients. Baseline characteristics were not significantly different between the two groups. Remdesivir was administered an average of 7.42 days from symptom onset. The proportions of clinical recovery of the remdesivir and supportive care group at HD 14 (56.3% and 39.5%) and HD 28 (87.5% and 78.9%) were not statistically different. The proportion of patients requiring MV support by HD 28 was significantly lower in the remdesivir group than in the supportive care group (22.9% vs. 44.7%, P = 0.032), and MV duration was significantly shorter in the remdesivir group (average, 1.97 vs. 5.37 days; P = 0.017). Analysis of upper respiratory tract specimens demonstrated that increases of Ct value from HD 1–5 to 11–15 were significantly greater in the remdesivir group than the supportive care group (average, 10.19 vs. 5.36; P = 0.007), and the slope of the Ct value increase was also significantly steeper in the remdesivir group (average, 5.10 vs. 2.68; P = 0.007). Conclusion The remdesivir group showed clinical and virologic benefit in terms of MV requirement and viral load reduction, supporting remdesivir treatment for severe COVID-19.