Nerve growth factor (NGF) is a neurotrophic factor usually involved in the survival, differentiation, and growth of sensory neurons and nociceptive function. Yet, it has been suggested to play a role in the pathogenesis of osteoarthritis (OA). Previous studies suggested a possible relationship between NGF and OA; however, the underlying mechanisms remain unknown. Therefore, we investigated the impact of NGF in chondrogenesis using human induced pluripotent stem cells (hiPSCs)-derived chondrogenic pellets. To investigate how NGF affects the cartilage tissue, hiPSC-derived chondrogenic pellets were treated with NGF on day 3 of differentiation, expression of chondrogenic, hypertrophic, and fibrotic markers was confirmed. Also, inflammatory cytokine arrays were performed using the culture medium of the NGF treated chondrogenic pellets. As a result, NGF treatment decreased the expression of pro-chondrogenic markers by approximately 2∼4 times, and hypertrophic (pro-osteogenic) markers and fibrotic markers were increased by approximately 3-fold or more in the NGF-treated cartilaginous pellets. In addition, angiogenesis was upregulated by approximately 4-fold or more, bone formation by more than 2-fold, and matrix metalloproteinase induction by more than 2-fold. These inflammatory cytokine array were using the NGF-treated chondrogenic pellet cultured medium.Furthermore, it was confirmed by Western blot to be related to the induction of the glycogen synthase kinase-3 beta (GSK3β) pathway by NGF. In Conclusions, these findings provide valuable insights into the multifaceted role of NGF in cartilage hypertrophy and fibrosis, which might play a critical role in OA progression.

Nerve growth factor (NGF) is a neurotrophic factor usually involved in the survival, differentiation, and growth of sensory neurons and nociceptive function. Yet, it has been suggested to play a role in the pathogenesis of osteoarthritis (OA). Previous studies suggested a possible relationship between NGF and OA; however, the underlying mechanisms remain unknown. Therefore, we investigated the impact of NGF in chondrogenesis using human induced pluripotent stem cells (hiPSCs)-derived chondrogenic pellets. To investigate how NGF affects the cartilage tissue, hiPSC-derived chondrogenic pellets were treated with NGF on day 3 of differentiation, expression of chondrogenic, hypertrophic, and fibrotic markers was confirmed. Also, inflammatory cytokine arrays were performed using the culture medium of the NGF treated chondrogenic pellets. As a result, NGF treatment decreased the expression of pro-chondrogenic markers by approximately 2∼4 times, and hypertrophic (pro-osteogenic) markers and fibrotic markers were increased by approximately 3-fold or more in the NGF-treated cartilaginous pellets. In addition, angiogenesis was upregulated by approximately 4-fold or more, bone formation by more than 2-fold, and matrix metalloproteinase induction by more than 2-fold. These inflammatory cytokine array were using the NGF-treated chondrogenic pellet cultured medium.Furthermore, it was confirmed by Western blot to be related to the induction of the glycogen synthase kinase-3 beta (GSK3β) pathway by NGF. In Conclusions, these findings provide valuable insights into the multifaceted role of NGF in cartilage hypertrophy and fibrosis, which might play a critical role in OA progression.

Nerve growth factor (NGF) is a neurotrophic factor usually involved in the survival, differentiation, and growth of sensory neurons and nociceptive function. Yet, it has been suggested to play a role in the pathogenesis of osteoarthritis (OA). Previous studies suggested a possible relationship between NGF and OA; however, the underlying mechanisms remain unknown. Therefore, we investigated the impact of NGF in chondrogenesis using human induced pluripotent stem cells (hiPSCs)-derived chondrogenic pellets. To investigate how NGF affects the cartilage tissue, hiPSC-derived chondrogenic pellets were treated with NGF on day 3 of differentiation, expression of chondrogenic, hypertrophic, and fibrotic markers was confirmed. Also, inflammatory cytokine arrays were performed using the culture medium of the NGF treated chondrogenic pellets. As a result, NGF treatment decreased the expression of pro-chondrogenic markers by approximately 2∼4 times, and hypertrophic (pro-osteogenic) markers and fibrotic markers were increased by approximately 3-fold or more in the NGF-treated cartilaginous pellets. In addition, angiogenesis was upregulated by approximately 4-fold or more, bone formation by more than 2-fold, and matrix metalloproteinase induction by more than 2-fold. These inflammatory cytokine array were using the NGF-treated chondrogenic pellet cultured medium.Furthermore, it was confirmed by Western blot to be related to the induction of the glycogen synthase kinase-3 beta (GSK3β) pathway by NGF. In Conclusions, these findings provide valuable insights into the multifaceted role of NGF in cartilage hypertrophy and fibrosis, which might play a critical role in OA progression.

Background: This study aimed to generate a Z score calculation model for coronary artery diameter of normal children and adolescents to be adopted as the standard calculation method with consensus in clinical practice. Methods: This study was a retrospective, multicenter study that collected data from multiple institutions across South Korea. Data were analyzed to determine the model that best fit the relationship between the diameter of coronary arteries and independent demographic parameters. Linear, power, logarithmic, exponential, and square root polynomial models were tested for best fit. Results: Data of 2,030 subjects were collected from 16 institutions. Separate calculation models for each sex were developed because the impact of demographic variables on the diameter of coronary arteries differs according to sex. The final model was the polynomial formula with an exponential relationship between the diameter of coronary arteries and body surface area using the DuBois formula. Conclusion A new coronary artery diameter Z score model was developed and is anticipated to be applicable in clinical practice. The new model will help establish a consensus-based Z score model.

Background and Objectives: Ultimaster™, a third-generation sirolimus-eluting stent using biodegradable polymer, has been introduced to overcome long term adverse vascular events, such as restenosis or stent thrombosis. In the present study, we aimed to evaluate the 12-month clinical outcomes of Ultimaster™ stents in Korean patients with coronary artery disease. Methods: This study is a multicenter, prospective, observational registry across 12 hospitals. To reflect real-world clinical evidence, non-selective subtypes of patients and lesions were included in this study. The study end point was target lesion failure (TLF) (the composite of cardiac death, target vessel myocardial infarction [MI], and target lesion revascularization [TLR]) at 12-month clinical follow up. Results: A total of 576 patients were enrolled between November 2016 and May 2021. Most of the patients were male (76.5%), with a mean age of 66.0±11.2 years. Among the included patients, 40.1% had diabetes mellitus (DM) and 67.9% had acute coronary syndrome (ACS).At 12 months, the incidence of TLF was 4.1%. The incidence of cardiac death was 1.5%, MI was 1.0%, TLR was 2.7%, and stent thrombosis was 0.6%. In subgroup analysis based on the presence of ACS, DM, hypertension, dyslipidemia, or bifurcation, there were no major differences in the incidence of the primary endpoint. Conclusions The present registry shows that Ultimaster™ stent is safe and effective for routine real-world clinical practice in non-selective Korean patients, having a low rate of adverse events at least up to 12 months.

Objectives: Alcohol is metabolized to acetaldehyde by alcohol dehydrogenase enzyme in the liver and then acetaldehyde is metabolized to acetone by aldehyde dehydrogenase (ALDH) in the liver. There are two main ALDH enzymes which metabolize the acetaldehyde produced during ethanol oxidation. In particular, in the presence of the ALDH2 1*2 allele, the activity of the ALDH 2 enzyme is lowered. As a result, acetaldehyde metabolism is slowed down and acetaldehyde accumulates in the body compared to the ALDH2 1*1 allele. There are many studies that have investigated the blood acetaldehyde concentration according to the ALDH2 genotype, but there are few studies to compare this with age. So we investigated the blood acetaldehyde concentration according to ALDH2 genotype, age and gender. Methods: According to the ALDH2 genotype, we divided the group by gender and age. We divided the age group in to three groups which ranged from 20 to 34 years old, from 35 to 49 years old, and lastly from 50 to 64 years old. And then we collected blood samples after 15 min, 30 min, 1 hr, 2 hr, 3 hr, 4 hr, 5 hr and 15 hr of after drinking to measure the blood acetaldehyde concentration. Results: In ALDH2 1*2 allele group, there are significant differences of the blood acetaldehyde concentration between the age groups. In ALDH2 1*2 allele and male group, there are significant differences of the blood acetaldehyde concentration between the age groups. Conclusions There are significant differences of the blood acetaldehyde concentration between the age groups according to ALDH2 genotype. Also, there are significant differences of the blood acetaldehyde concentration between the age groups with male gender and ALDH2 1*2 allele. Studies about other factors that may influence the blood acetaldehyde concentration are needed.

Background: Exercise capacity is known to be an independent predictor of cardiovascular events and mortality. However, most previous studies were based on Western populations.Further study is warranted for Asian patients according to ethnic or national standards. We aimed to compare prognostic values of Korean and Western nomograms for exercise capacity in Korean patients with cardiovascular disease (CVD). Methods: In this retrospective cohort study, we enrolled 1,178 patients (62 ± 11 years;78% male) between June 2015 and May 2020, who were referred for cardiopulmonary exercise testing in our cardiac rehabilitation program. The median follow-up period was 1.6 years. Exercise capacity was measured in metabolic equivalents by direct gas exchange method during the treadmill test. The nomogram for exercise capacity from healthy Korean individuals and a previous landmark Western study was used to determine the percentage of predicted exercise capacity. The primary endpoint was the composite of major adverse cardiovascular events (MACE; all-cause death, myocardial infarction, repeat revascularization, stroke and hospitalization for heart failure). Results: A multivariate analysis showed that the risk of primary endpoint was more than double (hazard ratio [HR], 2.20; 95% confidence interval [CI], 1.10–4.40) in the patients with lower exercise capacity (< 85% of predicted) by Korean nomogram. The lower exercise capacity was one of the strong independent predictors along with left ventricular ejection fraction, age, and level of hemoglobin. However, the lower exercise capacity by Western nomogram could not predict the primary endpoint (HR, 1.33; 95% CI, 0.85–2.10). Conclusion Korean patients with CVD with lower exercise capacity have higher risk of MACE.Considering inter-ethnic differences in cardiorespiratory fitness, the Korean nomogram provides more suitable reference values than the Western nomogram to determine lower exercise capacity and predict cardiovascular events in Korean patients with CVD.

Objectives: The effectiveness of drugs currently used in medication, which is important in the treatment of alcohol use disorders, is limited. Recently, ondansetron which acts as 5-HT3 receptor antagonist, has been studied and proved possibility as new medication for alcohol use disorder. Meanwhile, there are studies supporting that 5-HT1A receptors are related to addictive behavior. Considering those studies, we expect that vortioxetine, which acts as both 5-HT3 receptor antagonist and 5-HT1A receptor agonist, may be effective in treatment of alcohol use disorder. The purpose of this study is to examine the effect of vortioxetine on alcohol intake of C57BL/6 mice. Methods: In this study C57BL/6 mice were randomly assigned to normal saline group, vortioxetine 10 mg/kg group and vortioxetine 1 mg/kg group. To study effect of vortioxetine on alcohol, water, food intake and body weight of mice, we administered each medication for 14 days. Results: The overall alcohol intake was different between the three groups (PGroup=0.021), and alcohol intake in vortioxetine 10 mg/kg group was significantly lower than one in placebo group. Change across time points (PTime<0.001) and the interaction between group and time (PGroup×Time =0.016) were also significant. However, there were no significant differences between the three groups in water, food intake and body weight. Conclusions These results indicated that administration of high dose vortioxetine reduced alcohol intake of mice.Therefore, it is necessary to conduct clinical studies to examine the effectiveness of vortioxetine as a new treatment for alcohol use disorder.

Langerhans cell histiocytosis (LCH) is reported less frequently in adults than in children. The most common site of involvement in adults is the bone, accounting for 30-50% of cases. The gastrointestinal tract is very rare, accounting for approximately 2%. We present a case of Langerhans cell histiocytosis that simultaneously invaded multiple organs, including the stomach and colon, in an adult. A 37-year-old woman with no underlying disease complained of chest discomfort and a palpable right submandibular mass. A right Level II neck mass and mediastinal LN enlargement were confirmed on the pharynx and chest CT scan. Multiple subepithelial masses with central ulceration and erosion were observed in the corpus and fundus on the esophagogastroduodenoscopy and in the right colon on the colonoscopy. The histopathology findings were the same in each tissue biopsied from the stomach, colon, and right neck lymph nodes. Langerhans cells with classical reniform nuclei and prominent eosinophils invaded the normal glands, and S100 and CD1a were positive in the immunohistochemical stain. Gastrointestinal involvement of LCH in adults is rare, asymptomatic,and can involve multiple digestive organs simultaneously, so upper endoscopy and colonoscopy should be considered for a diagnosis.

Purpose: Alpha-fetoprotein (AFP) is a prognostic marker for hepatocellular carcinoma (HCC). We investigated the prognostic value of AFP levels in patients who achieved complete response (CR) to transarterial chemoembolization (TACE) for HCC. Materials and Methods: Between 2005 and 2018, 890 patients with HCC who achieved a CR to TACE were recruited. An AFP responder was defined as a patient who showed elevated levels of AFP (>10 ng/mL) during TACE, but showed normalization or a >50% reduction in AFP levels after achieving a CR. Results: Among the recruited patients, 569 (63.9%) with naïve HCC and 321 (36.1%) with recurrent HCC after complete resection were treated. Before TACE, 305 (34.3%) patients had multiple tumors, 219 (24.6%) had a maximal tumor size >3 cm, and 22 (2.5%) had portal vein tumor thrombosis. The median AFP level after achieving a CR was 6.36 ng/mL. After a CR, 473 (53.1%) patients experienced recurrence, and 417 (46.9%) died [median progression-free survival (PFS) and overall survival (OS) of 16.3 and 62.8 months, respectively]. High AFP levels at CR (>20 ng/mL) were independently associated with a shorter PFS [hazard ratio (HR)=1.403] and OS (HR=1.284), together with tumor multiplicity at TACE (HR=1.518 and 1.666, respectively). AFP non-responders at CR (76.2%, n=359 of 471) showed a shorter PFS (median 10.5 months vs. 15.5 months, HR=1.375) and OS (median 41.4 months vs. 61.8 months, HR=1.424) than AFP responders (all p=0.001). Conclusion High AFP levels and AFP non-responders were independently associated with poor outcomes after TACE. AFP holds clinical implications for detailed risk stratification upon achieving a CR after TACE.