1.Toxicity and efficacy study of a combination of two retinoic acids in an ApoE knockout mouse model of atherosclerosis
Da Som JEONG ; Ji-Young LEE ; Hyo-Jeong HAN ; Soo Min KO ; Dong Hyun LEE ; Yerin LEE ; Young-Sik PARK ; Byong-Cheol SHIN ; Woo-Chan SON
The Korean Journal of Physiology and Pharmacology 2025;29(2):179-189
Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE -/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE –/–mice. This study highlights PA9RA's potential as a promising therapeutic agent for atherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.
2.Higher Physical Activity is Associated with Reduced Lower Urinary Tract Symptoms in Korean Men
Seo Eun HWANG ; Jae Moon YUN ; Su Hwan CHO ; Kyungha MIN ; Ji Young KIM ; Hyuktae KWON ; Jin Ho PARK
The World Journal of Men's Health 2025;43(1):166-173
Purpose:
Identifying and managing risk factors for lower urinary tract symptoms (LUTS) is crucial because it impacts the quality of life of elderly individuals. Lifestyle factors, including physical activity (PA), and their relationship with LUTS have not been well studied. This objective of this study was to investigate the association between PA and LUTS.
Materials and Methods:
A total of 7,296 men were included in this cross-sectional study. PA was quantified in metabolic equivalent (MET)-hours per week, and LUTS severity was assessed using the international prostate symptom score. Logistic regression was used to analyze the association between PA and LUTS, including voiding and storage symptoms.
Results:
The average age of the participants was 57.8 years, and the prevalence of LUTS was 41.3%. After adjusting for potential confounders, PA was inversely associated with the prevalence and severity of moderate-to-severe LUTS, showing a dose-response pattern (all p for trend <0.01). Compared to the minimal activity group, which engaged in <5 MET-hours per week of PA, the odds ratios for moderate to severe LUTS were 0.83 (95% confidence interval [CI]: 0.72–0.97) for men engaging in 15–30 MET-hours per week, 0.82 (95% CI: 0.71–0.95) for 30–60 MET-hours per week, and 0.72 (95% CI: 0.62–0.84) for ≥60 MET-hours per week. The possible protective effect of PA was still observed in the additional analysis for voiding and storage symptoms showing the same dose-response pattern (all p for trend <0.01).
Conclusions
A higher PA level was associated with a lower prevalence and severity of total, voiding, and storage LUTS in a dose-dependent manner in Korean men.
3.The Application of L-Serine-Incorporated Gelatin Sponge into the Calvarial Defect of the Ovariectomized Rats
Yoon-Jo LEE ; Ji-Hyeon OH ; Suyeon PARK ; Jongho CHOI ; Min-Ho HONG ; HaeYong KWEON ; Weon-Sik CHAE ; Xiangguo CHE ; Je-Yong CHOI ; Seong-Gon KIM
Tissue Engineering and Regenerative Medicine 2025;22(1):91-104
BACKGROUND:
Osteoporosis, characterized by decreased bone mineral density due to an imbalance between osteoblast and osteoclast activity, poses significant challenges in bone healing, particularly in postmenopausal women. Current treatments, such as bisphosphonates, are effective but associated with adverse effects like medication-related osteonecrosis of the jaw, necessitating safer alternatives.
METHODS:
This study investigated the use of L-serine-incorporated gelatin sponges for bone regeneration in calvarial defects in an ovariectomized rat model of osteoporosis. Thirty rats were divided into three groups: a control group, a group treated with a gelatin sponge containing an amino acid mixture, and a group treated with a gelatin sponge containing L-serine. Bone regeneration was assessed using micro-computed tomography (micro-CT) and histological analyses.
RESULTS:
The L-serine group showed a significant increase in bone volume (BV) and bone area compared to the control and amino acid groups. The bone volume to total volume (BV/TV) ratio was also significantly higher in the L-serine group.Immunohistochemical analysis demonstrated that L-serine treatment suppressed the expression of cathepsin K, a marker of osteoclast activity, while increasing serine racemase activity.
CONCLUSION
These findings suggest that L-serine-incorporated gelatin sponges not only enhance bone formation but also inhibit osteoclast-mediated bone resorption, providing a promising and safer alternative to current therapies for osteoporosis-related bone defects. Further research is needed to explore its clinical applications in human patients.
4.Clinical Significance of Various Pathogens Identified in Patients Experiencing Acute Exacerbations of COPD: A Multi-center Study in South Korea
Hyun Woo JI ; Soojoung YU ; Yun Su SIM ; Hyewon SEO ; Jeong-Woong PARK ; Kyung Hoon MIN ; Deog Kyeom KIM ; Hyun Woo LEE ; Chin Kook RHEE ; Yong Bum PARK ; Kyeong-Cheol SHIN ; Kwang Ha YOO ; Ji Ye JUNG
Tuberculosis and Respiratory Diseases 2025;88(2):292-302
Background:
Respiratory infections play a major role in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study assessed the prevalence of bacterial and viral pathogens and their clinical impact on patients with AECOPD.
Methods:
This retrospective study included 1,186 patients diagnosed with AECOPD at 28 hospitals in South Korea between 2015 and 2018. We evaluated the identification rates of pathogens, basic patient characteristics, clinical features, and the factors associated with infections by potentially drug-resistant (PDR) pathogens using various microbiological tests.
Results:
Bacteria, viruses, and both were detected in 262 (22.1%), 265 (22.5%), and 129 (10.9%) of patients, respectively. The most common pathogens included Pseudomonas aeruginosa (17.8%), Mycoplasma pneumoniae (11.2%), Streptococcus pneumoniae (9.0%), influenza A virus (19.0%), rhinovirus (15.8%), and respiratory syncytial virus (6.4%). Notably, a history of pulmonary tuberculosis (odds ratio [OR], 1.66; p=0.046), bronchiectasis (OR, 1.99; p=0.032), and the use of a triple inhaler regimen within the past 6 months (OR, 2.04; p=0.005) were identified as significant factors associated with infection by PDR pathogens. Moreover, patients infected with PDR pathogens exhibited extended hospital stays (15.9 days vs. 12.4 days, p=0.018) and higher intensive care unit admission rates (15.9% vs. 9.5%, p=0.030).
Conclusion
This study demonstrates that a variety of pathogens are involved in episodes of AECOPD. Nevertheless, additional research is required to confirm their role in the onset and progression of AECOPD.
5.Development and Application of New Risk-Adjustment Models to Improve the Current Model for Hospital Standardized Mortality Ratio in South Korea
Hyeki PARK ; Ji-Sook CHOI ; Min Sun SHIN ; Soomin KIM ; Hyekyoung KIM ; Nahyeong IM ; Soon Joo PARK ; Donggyo SHIN ; Youngmi SONG ; Yunjung CHO ; Hyunmi JOO ; Hyeryeon HONG ; Yong-Hwa HWANG ; Choon-Seon PARK
Yonsei Medical Journal 2025;66(3):179-186
Purpose:
This study assessed the validity of the hospital standardized mortality ratio (HSMR) risk-adjusted model by comparing models that include clinical information and the current model based on administrative information in South Korea.
Materials and Methods:
The data of 53976 inpatients were analyzed. The current HSMR risk-adjusted model (Model 1) adjusts for sex, age, health coverage, emergency hospitalization status, main diagnosis, surgery status, and Charlson Comorbidity Index (CCI) using administrative data. As candidate variables, among clinical information, the American Society of Anesthesiologists score, Acute Physiology and Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) 3, present on admission CCI, and cancer stage were collected. Surgery status, intensive care in the intensive care unit, and CCI were selected as proxy variables among administrative data. In-hospital death was defined as the dependent variable, and a logistic regression analysis was performed. The statistical performance of each model was compared using C-index values.
Results:
There was a strong correlation between variables in the administrative data and those in the medical records. The C-index of the existing model (Model 1) was 0.785; Model 2, which included all clinical data, had a higher C-index of 0.857. In Model 4, in which APACHE II and SAPS 3 were replaced with variables recorded in the administrative data from Model 2, the C-index further increased to 0.863.
Conclusion
The HSMR assessment model improved when clinical data were adjusted. Simultaneously, the validity of the evaluation method could be secured even if some of the clinical information was replaced with the information in the administrative data.
6.Arthroscopic scaphocapitate fusion with lunate preservation without autologous bone grafts for Lichtman stage III Kienböck disease: a retrospective observational study
Archives of hand and microsurgery 2025;30(1):43-50
Purpose:
This study aimed to evaluate the outcomes of arthroscopic scaphocapitate fusion with lunate preservation, without autologous bone grafts, in stage III Kienböck disease, which causes significant wrist dysfunction due to lunate necrosis.
Methods:
Nine patients with stage III Kienböck disease underwent arthroscopic scaphocapitate fusion with lunate preservation from 2017 to 2022. Bone substitutes were used instead of autologous bone grafts: demineralized bone matrix, allogenic cancellous bone chips, and a bone substitute composed of hydroxyapatite combined with recombinant human bone morphogenetic protein-2. The clinical outcomes assessed were pain visual analogue scale (VAS), grip strength, wrist range of motion (ROM), Patient-Rated Wrist Evaluation (PRWE), and Disabilities of the Arm, Shoulder, and Hand (DASH) scores. Radiological assessments included bone union and modified carpal height ratio (MCHR).
Results:
At a mean follow-up of 22.7 months, all patients achieved bone union, with an average time to union of 8 weeks. Significant improvements were observed in wrist ROM (mean increase from 58.3° to 75.6°, p=0.001), grip strength (29.4% to 71.8% of the contralateral side, p<0.001), DASH scores (43.9 to 17.5, p<0.001), PRWE scores (45.2 to 18.0, p<0.001), and pain VAS (5.7 to 2.9, p<0.001). The mean MCHR decreased slightly from 1.41 to 1.39 (p<0.001).
Conclusion
Arthroscopic scaphocapitate fusion with lunate preservation, without autologous bone grafts, effectively improved pain, function, and anatomical outcomes in stage III Kienböck disease. Further research is needed to validate these findings.
7.The Cancer Clinical Library Database (CCLD) from the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) Project
Sangwon LEE ; Yeon Ho CHOI ; Hak Min KIM ; Min Ah HONG ; Phillip PARK ; In Hae KWAK ; Ye Ji KANG ; Kui Son CHOI ; Hyun-Joo KONG ; Hyosung CHA ; Hyun-Jin KIM ; Kwang Sun RYU ; Young Sang JEON ; Hwanhee KIM ; Jip Min JUNG ; Jeong-Soo IM ; Heejung CHAE
Cancer Research and Treatment 2025;57(1):19-27
The common data model (CDM) has found widespread application in healthcare studies, but its utilization in cancer research has been limited. This article describes the development and implementation strategy for Cancer Clinical Library Databases (CCLDs), which are standardized cancer-specific databases established under the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) project by the Korean Ministry of Health and Welfare. Fifteen leading hospitals and fourteen academic associations in Korea are engaged in constructing CCLDs for 10 primary cancer types. For each cancer type-specific CCLD, cancer data experts determine key clinical data items essential for cancer research, standardize these items across cancer types, and create a standardized schema. Comprehensive clinical records covering diagnosis, treatment, and outcomes, with annual updates, are collected for each cancer patient in the target population, and quality control is based on six-sigma standards. To protect patient privacy, CCLDs follow stringent data security guidelines by pseudonymizing personal identification information and operating within a closed analysis environment. Researchers can apply for access to CCLD data through the K-CURE portal, which is subject to Institutional Review Board and Data Review Board approval. The CCLD is considered a pioneering standardized cancer-specific database, significantly representing Korea’s cancer data. It is expected to overcome limitations of previous CDMs and provide a valuable resource for multicenter cancer research in Korea.
8.Enhancing Identification of High-Risk cN0 Lung Adenocarcinoma Patients Using MRI-Based Radiomic Features
Harim KIM ; Jonghoon KIM ; Soohyun HWANG ; You Jin OH ; Joong Hyun AHN ; Min-Ji KIM ; Tae Hee HONG ; Sung Goo PARK ; Joon Young CHOI ; Hong Kwan KIM ; Jhingook KIM ; Sumin SHIN ; Ho Yun LEE
Cancer Research and Treatment 2025;57(1):57-69
Purpose:
This study aimed to develop a magnetic resonance imaging (MRI)–based radiomics model to predict high-risk pathologic features for lung adenocarcinoma: micropapillary and solid pattern (MPsol), spread through air space, and poorly differentiated patterns.
Materials and Methods:
As a prospective study, we screened clinical N0 lung cancer patients who were surgical candidates and had undergone both 18F-fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET/CT) and chest CT from August 2018 to January 2020. We recruited patients meeting our proposed imaging criteria indicating high-risk, that is, poorer prognosis of lung adenocarcinoma, using CT and FDG PET/CT. If possible, these patients underwent an MRI examination from which we extracted 77 radiomics features from T1-contrast-enhanced and T2-weighted images. Additionally, patient demographics, maximum standardized uptake value on FDG PET/CT, and the mean apparent diffusion coefficient value on diffusion-weighted image, were considered together to build prediction models for high-risk pathologic features.
Results:
Among 616 patients, 72 patients met the imaging criteria for high-risk lung cancer and underwent lung MRI. The magnetic resonance (MR)–eligible group showed a higher prevalence of nodal upstaging (29.2% vs. 4.2%, p < 0.001), vascular invasion (6.5% vs. 2.1%, p=0.011), high-grade pathologic features (p < 0.001), worse 4-year disease-free survival (p < 0.001) compared with non-MR-eligible group. The prediction power for MR-based radiomics model predicting high-risk pathologic features was good, with mean area under the receiver operating curve (AUC) value measuring 0.751-0.886 in test sets. Adding clinical variables increased the predictive performance for MPsol and the poorly differentiated pattern using the 2021 grading system (AUC, 0.860 and 0.907, respectively).
Conclusion
Our imaging criteria can effectively screen high-risk lung cancer patients and predict high-risk pathologic features by our MR-based prediction model using radiomics.
9.Clinicopathological differences in the activation pattern of the complement system between pediatric and adult lupus nephritis: a single centered retrospective study in Korea
Min Ji PARK ; Man Hoon HAN ; Mee-seon KIM ; Yong-Jin KIM ; Sang Jin LEE ; Dongsub KIM ; Hee Sun BAEK ; Min Hyun CHO
Childhood Kidney Diseases 2025;29(1):24-31
Purpose:
Lupus nephritis (LN) can be caused by the complement activation. This study aimed to investigate the differences and clinical implications of the activation pattern of the complement system for pediatric and adult LN patients.
Methods:
We retrospectively reviewed the medical records of 40 patients (14 pediatric and 26 adult patients) diagnosed with LN through kidney biopsy.
Results:
The mean ages at diagnosis of pediatric and adult patients were 11.7±2.92 and 37.3±13.5 years, respectively. At the first LN diagnosis, compared with adult patients, pediatric patients had a higher estimated glomerular filtration rate and milder proteinuria; however, there was no statistical significance. The age-adjusted mean serum complement 3 value was significantly lower in the pediatric group (33.0±11.3 mg/dL) than in the adult group (50.8±25.2 mg/dL) (P<0.01). Based on the findings of kidney biopsy, no significant differences were observed in the severity of pathologic classification and the positive rate of complements between adults and children. However, the chronicity index score of adult patients was significantly higher than that of pediatric patients and in the case of complement 4d, despite a similar positive rate, the intensity was significantly stronger for adults (2.35±0.83 vs. 1.54±0.52, (P=0.04).
Conclusions
The activation pattern of the complement system in LN differs clinicopathologically between pediatric and adult patients and these differences might play an important role in the age-dependent prognosis of LN.
10.Exploring methylation signatures for high de novo recurrence risk in hepatocellular carcinoma
Da-Won KIM ; Jin Hyun PARK ; Suk Kyun HONG ; Min-Hyeok JUNG ; Ji-One PYEON ; Jin-Young LEE ; Kyung-Suk SUH ; Nam-Joon YI ; YoungRok CHOI ; Kwang-Woong LEE ; Young-Joon KIM
Clinical and Molecular Hepatology 2025;31(2):563-576
Background/Aims:
Hepatocellular carcinoma (HCC) exhibits high de novo recurrence rates post-resection. Current post-surgery recurrence prediction methods are limited, emphasizing the need for reliable biomarkers to assess recurrence risk. We aimed to develop methylation-based markers for classifying HCC patients and predicting their risk of de novo recurrence post-surgery.
Methods:
In this retrospective cohort study, we analyzed data from HCC patients who underwent surgical resection in Korea, excluding those with recurrence within one year post-surgery. Using the Infinium Methylation EPIC array on 140 samples in the discovery cohort, we classified patients into low- and high-risk groups based on methylation profiles. Distinctive markers were identified through random forest analysis. These markers were validated in the cancer genome atlas (n=217), Validation cohort 1 (n=63) and experimental Validation using a methylation-sensitive high-resolution melting (MS-HRM) assay in Validation cohort 1 and Validation cohort 2 (n=63).
Results:
The low-risk recurrence group (methylation group 1; MG1) showed a methylation average of 0.73 (95% confidence interval [CI] 0.69–0.77) with a 23.5% recurrence rate, while the high-risk group (MG2) had an average of 0.17 (95% CI 0.14–0.20) with a 44.1% recurrence rate (P<0.03). Validation confirmed the applicability of methylation markers across diverse populations, showing high accuracy in predicting the probability of HCC recurrence risk (area under the curve 96.8%). The MS-HRM assay confirmed its effectiveness in predicting de novo recurrence with 95.5% sensitivity, 89.7% specificity, and 92.2% accuracy.
Conclusions
Methylation markers effectively classified HCC patients by de novo recurrence risk, enhancing prediction accuracy and potentially offering personalized management strategies.

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