1.Network meta-analysis and validation study of expanded liver transplantation criteria for hepatocellular carcinoma: Significant role of alpha-fetoprotein
Dongman YU ; Yeongseok HWANG ; Jin-Sung JU ; Subin HEO ; Seon-Ok KIM ; Sang Hyun CHOI ; Gi-Won SONG ; Jihyun AN ; Ju Hyun SHIM
Clinical and Molecular Hepatology 2026;32(2):751-771
Background/Aims:
Various expanded criteria (EC) for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) have been proposed to avoid the narrow nature of the Milan criteria (MC). To investigate which EC predicts more favorable outcomes in terms of overall survival (OS) and recurrence-free survival (RFS), we conducted a network meta-analysis (NMA).
Methods:
A database search was conducted on PubMed, Embase, and the Cochrane Library, to identify studies comparing OS and RFS between patients within the MC and those exceeding the MC but within the EC. Hazard ratios (HRs) were pooled using a random-effects NMA and validated in an in-house cohort of 1,008 LT recipients.
Results:
Among 22,466 articles identified, 35 studies with 45 pairwise comparisons were included in the NMA along with 8 different EC. The University of California San Francisco (HR, 1.43; 95% CI, 1.19–1.71), Up-to-Seven (HR, 1.50; 95% CI, 1.15–1.97), and Hangzhou criteria (HR, 1.69; 95% CI, 1.11–2.57) showed inferior OS to the MC. The MC ranked highest for both OS and RFS, followed by Metroticket 2.0 for OS and the Asan criteria for RFS. In the validation cohort, both Metroticket 2.0 and AFP model yielded more favorable HCC-specific mortality than other EC.
Conclusions
Several EC, of which those of Metroticket 2.0 were the best, yielded comparable outcomes to the MC. AFP-based EC such as Metroticket 2.0 and AFP model appeared to be useful in both the NMA and the validation cohort, suggesting a potential role in identifying selected low-risk patients beyond the MC.
2.Incidence rate and risk factors for interstitial nephritis in patients with ankylosing spondylitis: a nationwide population-based study
Subin HWANG ; Ye-Jee KIM ; Soo Min AHN ; Bon San KOO
Journal of Rheumatic Diseases 2026;33(2):102-110
Objective:
In this study, we aimed to investigate the incidence and risk factors for interstitial nephritis in patients with ankylosing spondylitis (AS).
Methods:
We retrospectively analyzed the claims records of patients diagnosed with AS in Korea’s Health Insurance Review and Assessment Service Database between 2016 and 2019. The Assessment of Spondyloarthritis International Society nonsteroidal anti-inflammatory drugs (NSAIDs) intake score was used to calculate the NSAID dosage over 1 year after AS diagnosis. The incidence rate of interstitial kidney disease was calculated as the number of events per 1,000 person-years. The risks associated with sex, age, Charlson Comorbidity Index, comorbidities, and concomitant medications were assessed using the Cox proportional hazards model, with results presented as hazard ratios (HRs) and 95% confidence intervals (CIs).
Results:
In total, 11,749 patients with AS were included in this study. Of these, 79 patients had interstitial nephritis, with an incidence rate of 2.50 per 1,000 person-years. In multivariable analysis, female sex (HR, 2.44; 95% CI, 1.56~3.83), hypertension (HR, 2.08; 95% CI, 1.15~3.76), and renal failure (HR, 3.70; 95% CI, 1.30~10.55) showed significant associations. However, NSAID use in the first year after AS diagnosis was not associated with interstitial nephritis occurrence.
Conclusion
The incidence of interstitial nephritis in patients with AS was 2.50 per 1,000 person-years, with female sex and comorbidities identified as significant risk factors. However, NSAID use during the first year after AS diagnosis was not associated with interstitial nephritis development.
3.Synergistic Exacerbation of Allergic Inflammation by Combined Exposure to Air-Pollutants in a Murine Model of Allergic Rhinitis
Joo-Hoo PARK ; Jee Won MOON ; Yeong-In JO ; Hwa Eun YANG ; Subin CHO ; Hyeongguk SON ; Hyun-Woo YANG ; Dae Jin SONG ; Il-Ho PARK
Clinical and Experimental Otorhinolaryngology 2026;19(1):86-96
Objectives:
Allergic rhinitis (AR) is a chronic inflammation of the nasal mucosa triggered by environmental allergens. Although its pathophysiology has been extensively investigated, the influence of environmental aggravating factors—particularly combined pollutant exposure—remains insufficiently characterized. This study aimed to assess the impact of coexposure to PM2.5, formaldehyde, and Zn on allergic inflammation in a murine AR model and to delineate the associated immunological and histopathological responses.
Methods:
Female BALB/c mice were sensitized with ovalbumin (OVA) and challenged intranasally to induce AR. On days 21–24, the mice were exposed to PM2.5, formaldehyde, and Zn, either individually or in combination with OVA. Allergic symptoms were evaluated through behavioral observation, while immune responses were assessed by analyzing nasal and bronchoalveolar lavage fluids (NALF and BALF), serum immunoglobulin levels, nasal histopathology, and cytokine profiles.
Results:
Combined exposure to PM2.5, formaldehyde, and Zn significantly intensified allergic inflammation compared with single exposures. Coexposure to PM2.5 and Zn led to synergistic increases in total and OVA-specific immunoglobulin E levels, eosinophilic infiltration, nasal rubbing, sneezing, and Th2/Th17 cytokine levels in NALF and BALF. Histological analysis demonstrated epithelial thickening and goblet cell hyperplasia after combined exposure. Other combinations, including PM2.5 with formaldehyde, also produced additive or modestly amplified inflammatory responses.
Conclusions
Coexposure to PM2.5, formaldehyde, and Zn aggravated allergic inflammation in an OVA-induced murine model, with PM2.5+Zn yielding the strongest synergistic effects. These findings emphasize the role of pollutant–pollutant interactions in allergic airway diseases and highlight the need for further research to clarify long-term health effects and relevance to human disease.
4.Scoping review of research trends in genetic factors related to metabolic syndrome in Koreans: using the data from Korean Genome and Epidemiology Study (KoGES)
Minyeong KIM ; Subin KIM ; Dayeon SHIN
Journal of Nutrition and Health 2025;58(1):131-152
Purpose:
Metabolic syndrome (MetS) is a condition in which multiple risk factors interact in a complex manner. Considerable attention has been directed towards the potential genetic contributions to its diverse mechanisms. Understanding these contributions is essential for reducing MetS and other chronic diseases and developing effective prevention strategies.Therefore, this study analyzed the research trends in academic papers exploring genetic factors related to MetS and its components in Koreans and attempted to identify areas requiring additional research.
Methods:
The scoping review method was used to evaluate studies that utilized the secondary data sets comprising the Korean Genome and Epidemiology Study. Articles published over the past 15 years were identified using the Research Information Sharing Service, Korean Studies Information Service System, DBpia, PubMed, and ScienceDirect databases.
Results:
Forty-seven published articles from 2010 to 2024 were included in the review.Research on the genetic factors linked to MetS has expanded since 2019, indicating significant advances in the field. The research included 18 studies on the polygenic risk score (PRS)/genetic risk score (GRS), 17 studies on single nucleotide polymorphisms (SNPs), six studies on two or more genes, four studies on DNA methylation, and two studies on copy number variations (CNVs). In PRS/GRS research, seven studies focused on the genes related to diseases. In SNP research, four studies examined the FTO gene. Studies on two or more genes included two studies, each on the genes associated with diabetes and high-density lipoprotein cholesterol. For DNA methylation, three studies focused on the TXNIP gene. Finally, in CNV research, one study was conducted on the LEPR gene and one on genes for hypertension.
Conclusion
The relatively low proportion of studies on DNA methylation and CNV presents limitations in understanding their associations with MetS. Expanded research utilizing diverse approaches and genetic variables is needed to overcome these limitations.
5.Incidence and Temporal Dynamics of Combined Infections in SARS-CoV-2-Infected Patients With Risk Factors for Severe Complications
Sin Young HAM ; Seungjae LEE ; Min-Kyung KIM ; Jaehyun JEON ; Eunyoung LEE ; Subin KIM ; Jae-Phil CHOI ; Hee-Chang JANG ; Sang-Won PARK
Journal of Korean Medical Science 2025;40(11):e38-
Background:
Coronavirus disease 2019 (COVID-19) is a newly emerged infectious disease that needs further clinical investigation. Characterizing the temporal pattern of combined infections in patients with COVID-19 may help clinicians understand the clinical nature of this disease and provide valuable diagnostic and therapeutic guidelines.
Methods:
We retrospectively analyzed COVID-19 patients isolated in four study hospitals in Korea for one year period from May 2021 to April 2022 when the delta and omicron variants were dominant. The temporal characteristics of combined infections based on specific diagnostic tests were analyzed.
Results:
A total of 16,967 COVID-19 patients were screened, 2,432 (14.3%) of whom underwent diagnostic microbiologic tests according to the clinical decision-making, 195 of whom had positive test results, and 0.55% (94/16,967) of whom were ultimately considered to have clinically meaningful combined infections. The median duration for the diagnosis of combined infections was 15 (interquartile range [IQR], 5–25) days after admission. The proportion of community-acquired coinfections (≤ 2 days after admission) was 11.7% (11/94), which included bacteremia (10/94, 10.63%) and tuberculosis (1/94, 1.06%). Combined infections after 2 days of admission were diagnosed at median 16 (IQR, 9–26) days, and included bacteremia (72.3%), fungemia (19.3%), cytomegalovirus (CMV) diseases (8.4%), Pneumocystis jerovecii pneumonia (PJP, 8.4%) and invasive pulmonary aspergillosis (IPA, 4.8%).
Conclusion
Among COVID-19 patients with risk factors for severe complications, 0.55% had laboratory-confirmed combined infections, which included community and nosocomial pathogens in addition to unusual pathogens such as CMV disease, PJP and IPA.
6.Atherosclerotic Cardiovascular Disease in Cancer Survivors: Current Evidence, Risk Prediction, Prevention, and Management
Arum CHOI ; Subin KIM ; Seonji KIM ; Iksung CHO ; Min Jae CHA ; Seng Chan YOU
Journal of Lipid and Atherosclerosis 2025;14(1):30-39
While advances in cancer treatment have led to improved survival rates, cancer survivors are at a significant risk of developing atherosclerotic cardiovascular disease (ASCVD).This review examines the risk, diagnosis, and prevention of ASCVD in this population.Cancer survivors, especially those diagnosed with certain types, face a significantly higher risk of developing ASCVD than the general population. We introduce the “triad model” to explain this increased risk of ASCVD among cancer patients. This model includes three interconnected components: common catalysts, cancer influence, and treatment impact.The factors contributing to this model are the shared risk factors between cancer and ASCVD, such as smoking, obesity, and systemic inflammation; the direct effects of cancer on cardiovascular health through chronic systemic inflammation and endothelial damage;and the significant effects of anticancer treatments, including chemotherapy and radiation, which can worsen cardiovascular complications and hasten the progression of ASCVD.Furthermore, cancer survivors are at a higher risk of developing and dying from ASCVD, highlighting the necessity for tailored guidelines and strategies for ASCVD prevention and management in this population. The review explores the utility of diagnostic tools, such as coronary artery calcium scoring, in predicting and managing ASCVD risk. It also emphasizes the importance of prevention strategies that include regular cardiovascular monitoring and lifestyle modifications. Finally, the relationship between cancer survival and cardiovascular health highlights the importance of integrated and comprehensive care approaches.Continued research, the development of prediction models, and specific preventative strategies are essential to improve cancer survivors’ overall health outcomes.
7.Research progress of occult lymph node metastasis in cN0 tongue squamous cell carcinoma
Wang SUBIN ; Wu ZHENG ; Han YAQIAN ; Wang HUI
Chinese Journal of Clinical Oncology 2025;52(4):198-201
Tongue squamous cell carcinoma is the most frequent malignant tumor in the oral cavity.The incidence of occult metastasis in early-stage tongue squamous cell carcinoma ranges from 19.81%to 61.8%.The sensitivity,specificity,and accuracy of currently employed diagnostic techniques vary among different research centers.Cervical lymph nodes in tongue squamous cell carcinoma exhibit certain regu-larities,with metastasis primarily occurring in ipsilateral levels Ⅰ,Ⅱ,and Ⅲ,and occasional occurrence of skip metastasis.Occult metastasis to cervical lymph nodes in tongue squamous cell carcinoma is influenced by various factors.The treatment approach for the neck remains controversial,with options including selective neck dissection,observation,and sentinel lymph node biopsy.This review aims to elaborate on the incidence of occult lymph node metastasis in patients with tongue squamous cell carcinoma,the distribution patterns of metastatic lymph nodes,the value of various diagnostic techniques in detecting occult metastasis,risk factors for occult metastasis,and strategies for neck management.
8.In Vivo Differentiation of Endogenous Bone Marrow-Derived Cells into Insulin-Producing Cells Using Four Soluble Factors
Seung-Ah LEE ; Subin KIM ; Seog-Young KIM ; Jong Yoen PARK ; Hye Seung JUNG ; Sung Soo CHUNG ; Kyong Soo PARK
Diabetes & Metabolism Journal 2025;49(1):150-159
Four soluble factors—putrescine, glucosamine, nicotinamide, and signal transducer and activator of transcription 3 (STAT3) inhibitor BP-1-102—were shown to differentiate bone marrow mononucleated cells (BMNCs) into functional insulin-producing cells (IPCs) in vitro. Transplantation of these IPCs improved hyperglycemia in diabetic mice. However, the role of endogenous BMNC regeneration in this effect was unclear. This study aimed to evaluate the effect of these factors on in vivo BMNC differentiation into IPCs in diabetic mice. Mice were orally administered the factors for 5 days, twice at 2-week intervals, and monitored for 45–55 days. Glucose tolerance, glucose-stimulated insulin secretion, and pancreatic insulin content were measured. Chimeric mice harboring BMNCs from insulin promoter luciferase/green fluorescent protein (GFP) transgenic mice were used to track endogenous BMNC fate. These factors lowered blood glucose levels, improved glucose tolerance, and enhanced insulin secretion. Immunostaining confirmed IPCs in the pancreas, showing the potential of these factors to induce β-cell regeneration and improve diabetes treatment.
9.Risk of Osteoporotic Fractures among Patients with Thyroid Cancer: A Nationwide Population-Based Cohort Study
Eu Jeong KU ; Won Sang YOO ; Yu Been HWANG ; Subin JANG ; Jooyoung LEE ; Shinje MOON ; Eun Kyung LEE ; Hwa Young AHN
Endocrinology and Metabolism 2025;40(2):225-235
Background:
The associations between thyroid cancer and skeletal outcomes have not been thoroughly investigated. We aimed to investigate the risk of osteoporotic fractures in patients with thyroid cancer compared to that in a matched control group.
Methods:
This retrospective cohort study included 2,514 patients with thyroid cancer and 75,420 matched controls from the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC, 2006–2019). The rates of osteoporotic fractures were analyzed, and associations with the levothyroxine dose were evaluated.
Results:
Patients with thyroid cancer had a significantly lower risk of fracture than did the control group (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.69 to 0.94; P=0.006). Patients diagnosed with thyroid cancer after the age of 50 years (older cancer group) had a significantly lower risk of fracture than did those in the control group (HR, 0.72; 95% CI, 0.6 to 0.85; P<0.001), especially those diagnosed with spinal fractures (HR, 0.66; 95% CI, 0.51 to 0.85; P=0.001). Patients in the older cancer group started osteoporosis treatment earlier than did those in the control group (65.5±7.5 years vs. 67.3±7.6 years, P<0.001). Additionally, a lower dose of levothyroxine was associated with a reduced risk of fractures.
Conclusion
In the clinical setting, the risk of fracture in women diagnosed with thyroid cancer after the age of 50 years was lower than that in the control group, which was caused by more proactive osteoporosis treatment in postmenopausal women with thyroid cancer.
10.Artificial Intelligence Models May Aid in Predicting Lymph Node Metastasis in Patients with T1 Colorectal Cancer
Ji Eun BAEK ; Hahn YI ; Seung Wook HONG ; Subin SONG ; Ji Young LEE ; Sung Wook HWANG ; Sang Hyoung PARK ; Dong-Hoon YANG ; Byong Duk YE ; Seung-Jae MYUNG ; Suk-Kyun YANG ; Namkug KIM ; Jeong-Sik BYEON
Gut and Liver 2025;19(1):69-76
Background/Aims:
Inaccurate prediction of lymph node metastasis (LNM) may lead to unnecessary surgery following endoscopic resection of T1 colorectal cancer (CRC). We aimed to validate the usefulness of artificial intelligence (AI) models for predicting LNM in patients with T1 CRC.
Methods:
We analyzed the clinical data, laboratory results, pathological reports, and endoscopic findings of patients who underwent radical surgery for T1 CRC. We developed AI models to predict LNM using four algorithms: regularized logistic regression classifier (RLRC), random forest classifier (RFC), CatBoost classifier (CBC), and the voting classifier (VC). Four histological factors and four endoscopic findings were included to develop AI models. Areas under the receiver operating characteristics curves (AUROCs) were measured to distinguish AI model performance in accordance with the Japanese Society for Cancer of the Colon and Rectum guidelines.
Results:
Among 1,386 patients with T1 CRC, 173 patients (12.5%) had LNM. The AUROC values of the RLRC, RFC, CBC, and VC models for LNM prediction were significantly higher (0.673, 0.640, 0.679, and 0.677, respectively) than the 0.525 suggested in accordance with the Japanese Society for Cancer of the Colon and Rectum guidelines (vs RLRC, p<0.001; vs RFC, p=0.001; vs CBC, p<0.001; vs VC, p<0.001). The AUROC value was similar between T1 colon versus T1 rectal cancers (0.718 vs 0.615, p=0.700). The AUROC value was also similar between the initial endoscopic resection and initial surgery groups (0.581 vs 0.746, p=0.845).
Conclusions
AI models trained on the basis of endoscopic findings and pathological features performed well in predicting LNM in patients with T1 CRC regardless of tumor location and initial treatment method.

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