Betulinic acid (3-beta-hydroxy-lup20[29]-en-28-oic acid) has attracted significant attention due to its diverse biological and pharmacological activities, including anti-inflammatory, antimicrobial, antiviral, antidiabetic, antimalarial, anti-human immunodeficiency virus, and antitumor effects. However, its effectiveness against oral cancer remains unknown. This study aimed to evaluate the effect of betulinic acid on the induction of apoptosis in FaDu human pharyngeal carcinoma cells by performing 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, LIVE/DEAD stain, 4',6-diamidino-2-phenylindole (DAPI) stain and western blot. In the MTT assay, LIVE/DEAD stain, and DAPI stain analyses, betulinic acid increased FaDu cell apoptosis in a concentration-dependent manner. Apoptosis induced by betulinic acid in FaDu cells was mediated by the expression of Fas and the activation of caspase-8, caspase-3, and poly (ADP-ribose) polymerase. Western blotting revealed that B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra large were downregulated, while Bcl-2-associated death promoter and Bcl-2-associated X protein were upregulated by betulinic acid in FaDu cells. These findings indicate that betulinic acid inhibits cell proliferation in FaDu human pharyngeal carcinoma cells and induces apoptosis through both apoptotic receptor-mediated exogenous apoptosis and mitochondrialmediated endogenous apoptosis pathways.

Purpose: As introduced, multimodal pain management bundle for ileostomy reversal may be considered to reduce postoperative pain and hospital stay. The aim of this study was to evaluate clinical efficacy of perioperative multimodal pain bundle for ileostomy. Methods: Medical records of patients who underwent ileostomy reversal after rectal cancer surgery from April 2017 to March 2020 were analyzed. Sixty-seven patients received multimodal pain bundle protocol with ileostomy reversal (group A) and 41 patients underwent closure of ileostomy with conventional pain management (group B). Results: Baseline characteristics, including age, sex, body mass index, American Society of Anesthesiologists classification, diabetes mellitus, and smoking history, were not significantly different between the groups. The pain score on postoperative day 1 was significant lower in group A (visual analog scale, 2.6 ± 1.3 vs. 3.2 ± 1.2; P = 0.013). Overall consumption of opioid in group A was significant less than group B (9.7 ± 9.5 vs. 21.2 ± 8.8, P < 0.001). Hospital stay was significantly shorter in group A (2.3 ± 1.5 days vs. 4.1 ± 1.5 days, P < 0.001). There were no significant differences between the groups in postoperative complication rate. Conclusion Multimodal pain protocol for ileostomy reversal could reduce postoperative pain, usage of opioid and hospital stay compared to conventional pain management.

Background: The benefits of transradial access (TRA) over transfemoral access (TFA) for bifurcation percutaneous coronary intervention (PCI) are uncertain because of the limited availability of device selection. This study aimed to compare the procedural differences and the in-hospital and long-term outcomes of TRA and TFA for bifurcation PCI using secondgeneration drug-eluting stents (DESs). Methods: Based on data from the Coronary Bifurcation Stenting Registry III, a retrospective registry of 2,648 patients undergoing bifurcation PCI with second-generation DES from 21 centers in South Korea, patients were categorized into the TRA group (n = 1,507) or the TFA group (n = 1,141). After propensity score matching (PSM), procedural differences, in-hospital outcomes, and device-oriented composite outcomes (DOCOs; a composite of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization) were compared between the two groups (772 matched patients each group). Results: Despite well-balanced baseline clinical and lesion characteristics after PSM, the use of the two-stent strategy (14.2% vs. 23.7%, P = 0.001) and the incidence of in-hospital adverse outcomes, primarily driven by access site complications (2.2% vs. 4.4%, P = 0.015), were significantly lower in the TRA group than in the TFA group. At the 5-year follow-up, the incidence of DOCOs was similar between the groups (6.3% vs. 7.1%, P = 0.639). Conclusion The findings suggested that TRA may be safer than TFA for bifurcation PCI using second-generation DESs. Despite differences in treatment strategy, TRA was associated with similar long-term clinical outcomes as those of TFA. Therefore, TRA might be the preferred access for bifurcation PCI using second-generation DES.

Subclinical hypothyroidism (SCH), characterized by elevated serum thyroid-stimulating hormone (TSH) levels and normal free thyroxine levels, usually presents without symptoms, and is often discovered incidentally during routine blood test. The Task Force of the Korean Thyroid Association Committee of Clinical Practice Guidelines has established a guideline to evaluate and manage SCH; the guideline emphasizes the implementation of diagnostic criteria based on the TSH reference range for Koreans and focuses on the proven health benefits of levothyroxine (LT4) treatment. Based on the Korea National Health and Nutrition Examination Survey (2013-2015), serum TSH level of 6.8 mIU/L is considered the reference value for SCH. SCH can be categorized as mild (TSH 6.8-10.0 mIU/L) or severe (TSH ＞10.0 mIU/L), and patients are classified as adults (age ＜70 years) or elderly patients (age ≥70years) depending on the health effects of LT4 treatment. An initial increase in serum TSH levels should be reassessed with a subsequent measurement, along with the thyroid peroxidase antibody test, preferably 2-3 months after the initial evaluation. Usually, LT4 treatment is not recommended for mild SCH in adults; however, treatment is necessary for severe SCH in patients with underlying coronary artery disease or heart failure and can be considered for coexisting dyslipidemia. LT4 treatment is not recommended for mild or even severe SCH in elderly patients, in general. Patients with SCH who receive LT4 treatment, the LT4 dosage should be personalized, and serum TSH levels should be monitored to ensure optimal LT4 dosage (dosage that is neither excessive nor insufficient). Patients with SCH who do not receive LT4 treatment require periodic follow-up at appropriate testing intervals determined by disease severity. The guideline also provides several educational points applicable in clinical settings.

The present study was carried out to investigate the effect of Arctigenin on cell growth and the mechanism of cell death elicited by Arctigenin were examined in FaDu human pharyngeal carcinoma cells. To determine the apoptotic activity of Arctigenin in FaDu human pharyngeal carcinoma cells, cell viability assay, DAPI staining, caspase activation analysis, and immunoblotting were performed. Arctigenin inhibited the growth of cells in a dose-dependent manner and induced nuclear condensation and fragmentation. Arctigenin-treated cells showed caspase-3/7 activation and increased apoptosis versus control cells. FasL, a death ligand associated with extrinsic apoptotic signaling pathways, was up-regulated by Arctigenin treatment. Moreover, caspase-8, a part of the extrinsic apoptotic pathway, was activated by Arctigenin treatments. Expressions of anti-apoptotic factors such as Bcl-2 and Bcl-xL, components of the mitochondria-dependent intrinsic apoptosis pathway, significantly decreased following Arctigenin treatment. The expressions of pro-apoptotic factors such as BAX, BAD and caspase-9, and tumor suppressor -53 increased by Arctigenin treatments. In addition, Arctigenin activated caspase-3 and poly (ADP-ribose) polymerase (PARP) induced cell death. Arctigenin also inhibited the proliferation of FaDu cells by the suppression of p38, NF-κB, and Akt signaling pathways. These results suggest that Arctigenin may inhibit cell proliferation and induce apoptotic cell death in FaDu human pharyngeal carcinoma cells through both the mitochondria-mediated intrinsic pathway and the death receptormediated extrinsic pathway.

Background and Objectives: The aim of this study was to demonstrate the efficacy and safety of treatment with drug-coated balloon (DCB) in a large real-world population. Methods: Patients treated with DCBs were included in a multicenter observational registry that enrolled patients from 18 hospitals in Korea between January 2009 and December 2017. The primary outcome was target lesion failure (TLF) defined as a composite of cardiovascular death, target vessel myocardial infarction, and clinically indicated target lesion revascularization at 12 months. Results: The study included 2,509 patients with 2,666 DCB-treated coronary artery lesions (1,688 [63.3%] with in-stent restenosis [ISR] lesions vs. 978 [36.7%] with de novo lesions).The mean age with standard deviation was 65.7±11.3 years; 65.7% of the patients were men.At 12 months, the primary outcome, TLF, occurred in 179 (6.7%), 151 (8.9%), 28 (2.9%) patients among the total, ISR, and de novo lesion populations, respectively. A history of hypertension, diabetes, acute coronary syndrome, previous coronary artery bypass graft, reduced left ventricular ejection fraction, B2C lesion and ISR lesion were independent predictors of 12 months TLF in the overall study population. Conclusions This large multicenter DCB registry study revealed the favorable clinical outcome of DCB treatment in real-world practice in patient with ISR lesion as well as small de novo coronary lesion.

The aim of the present study was to investigate the physiological role of nicotinamide phosphoribosyltransferase (NAMPT) associated with odontogenic differentiation during tooth development in mice. Mouse dental papilla cell-23 (MDPC-23) cells cultured in differentiation media were stimulated with the specific NAMPT inhibitor, FK866, and Visfatin (NAMPT) for up to 10 days. The cells were evaluated after 0, 4, 7, and 10 days. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The mineralization assay was performed by staining MDPC-23 cells with Alizarin Red S solution. After cultivation, MDPC-23 cells were harvested for quantitative PCR or Western blotting. Analysis of variance was performed using StatView 5.0 software (SAS Institute Inc., Cary, NC, USA). Statistical significance was set at p < 0.05. The expression of NAMPT increased during the differentiation of murine odontoblast-like MDPC-23 cells. Furthermore, the up-regulation of NAMPT promoted odontogenic differentiation and accelerated mineralization through an increase in representative odontoblastic biomarkers, such as dentin sialophosphoprotein, dentin matrix protein-1, and alkaline phosphatase in MDPC-23 cells. However, treatment of the cells with the NAMPT inhibitor, FK866, attenuated odontogenic differentiation, as evidenced by the suppression of odontoblastic biomarkers. These data indicate that NAMPT regulated odontoblastic differentiation through the regulation of odontoblastic biomarkers. The increase in NAMPT expression in odontoblasts was closely related to the formation of the extracellular matrix and dentin via the Runx signaling pathway. Therefore, these data suggest that NAMPT is a critical regulator of odontoblast differentiation during tooth development.