1.Identification of signature gene set as highly accurate determination of metabolic dysfunction-associated steatotic liver disease progression
Sumin OH ; Yang-Hyun BAEK ; Sungju JUNG ; Sumin YOON ; Byeonggeun KANG ; Su-hyang HAN ; Gaeul PARK ; Je Yeong KO ; Sang-Young HAN ; Jin-Sook JEONG ; Jin-Han CHO ; Young-Hoon ROH ; Sung-Wook LEE ; Gi-Bok CHOI ; Yong Sun LEE ; Won KIM ; Rho Hyun SEONG ; Jong Hoon PARK ; Yeon-Su LEE ; Kyung Hyun YOO
Clinical and Molecular Hepatology 2024;30(2):247-262
Background/Aims:
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression.
Methods:
Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD.
Results:
After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort.
Conclusions
We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.
2.Hashimoto Thyroiditis and Mortality in Patients with Differentiated Thyroid Cancer: The National Epidemiologic Survey of Thyroid Cancer in Korea and Meta-Analysis
Injung YANG ; Jae Myung YU ; Hye Soo CHUNG ; Yoon Jung KIM ; Yong Kyun ROH ; Min Kyu CHOI ; Sung-ho PARK ; Young Joo PARK ; Shinje MOON
Endocrinology and Metabolism 2024;39(1):140-151
Background:
Many studies have shown that Hashimoto’s thyroiditis (HT) acts as a protective factor in differentiated thyroid cancer (DTC), but little is known about its effects on mortality. Therefore, this study was performed to reveal the prognosis of HT on mortality in patients with DTC.
Methods:
This study included two types of research results: retrospective cohort study using the National Epidemiologic Survey of Thyroid cancer (NEST) in Korea and meta-analysis study with the NEST data and eight selected studies.
Results:
Of the 4,398 patients with DTC in NEST, 341 patients (7.8%) died during the median follow-up period of 15 years (interquartile range, 12.3 to 15.6). Of these, 91 deaths (2.1%) were related to DTC. HT was associated with a smaller tumor size and less aggressive DTC. In Cox regression analysis after adjusting for age and sex, patients with HT showed a significantly lower risk of all-cause death (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52 to 0.96) and DTC-related death (HR, 0.33; 95% CI, 0.14 to 0.77). The analysis with inverse probability of treatment weight data adjusted for age, sex, and year of thyroid cancer registration showed similar association. The meta-analysis showed that patients with HT showed a lower risk of all-cause mortality (risk ratio [RR], 0.24; 95% CI, 0.13 to 0.47) and thyroid cancer-related mortality (RR, 0.23; 95% CI, 0.13 to 0.40) in comparison with patients without HT.
Conclusion
This study showed that DTC co-presenting with HT is associated with a low risk of advanced DTC and presents a low risk for all-cause and DTC-related death.
3.Association of Geriatric Depressive Symptoms and Government-Initiated Senior Employment Program: A Population-Based Study
Soyeon PARK ; Yeojin KIM ; Sunwoo YOON ; You Jin NAM ; Sunhwa HONG ; Yong Hyuk CHO ; Sang Joon SON ; Chang Hyung HONG ; Jai Sung NOH ; Hyun Woong ROH
Psychiatry Investigation 2024;21(3):284-293
Objective:
The impact of the government-initiated senior employment program (GSEP) on geriatric depressive symptoms is underexplored. Unearthing this connection could facilitate the planning of future senior employment programs and geriatric depression interventions. In the present study, we aimed to elucidate the possible association between geriatric depressive symptoms and GSEP in older adults.
Methods:
This study employed data from 9,287 participants aged 65 or older, obtained from the 2020 Living Profiles of Older People Survey. We measured depressive symptoms using the Korean version of the 15-item Geriatric Depression Scale. The principal exposure of interest was employment status and GSEP involvement. Data analysis involved multiple linear regression.
Results:
Employment, independent of income level, showed association with decreased depressive symptoms compared to unemployment (p<0.001). After adjustments for confounding variables, participation in GSEP jobs showed more significant reduction in depressive symptoms than non-GSEP jobs (β=-0.968, 95% confidence interval [CI]=-1.197 to -0.739, p<0.001 for GSEP jobs, β=-0.541, 95% CI=-0.681 to -0.401, p<0.001 for non-GSEP jobs). Notably, the lower income tertile in GSEP jobs showed a substantial reduction in depressive symptoms compared to all income tertiles in non-GSEP jobs.
Conclusion
The lower-income GSEP group experienced lower depressive symptoms and life dissatisfaction compared to non-GSEP groups regardless of income. These findings may provide essential insights for the implementation of government policies and community-based interventions.
4.Case report of unusual complication following thread lifting: an obstructive stone in the parotid duct
Yoon Kyu CHUNG ; Min-Seok KIM ; Jin Yong SHIN ; Nae-Ho LEE ; Ho Sung PARK ; Si-Gyun ROH
Archives of Aesthetic Plastic Surgery 2023;29(3):170-173
Advances in plastic surgery have included a shift toward less invasive procedures. To improve outcomes and avoid incisional surgery, numerous noninvasive face-lifting techniques have been studied. This includes thread-lifting, a technique that promises to correct facial aging with limited scarring, rapid recovery, and minimal complications. As the population ages, an increasing number of ordinary people in South Korea are undergoing thread lifting procedures for the purpose of rejuvenation. The procedure involves insertion of a thread under the skin into the subcutaneous tissue, using a long needle as a guide. Dents or barbs prevent the thread from slipping and provide uniform aggregation of soft tissue to create a new volume contour when the thread is lifted. This procedure has gained worldwide popularity and is frequently performed. However, some minor complications have been reported. In this paper, we report an unusual complication: an obstructive stone in the parotid (Stensen) duct after a thread-lifting procedure using nonabsorbable anchoring threads.
5.A Randomized Phase III Study of Patients With Advanced Gastric Adenocarcinoma Without Progression After Six Cycles of XELOX (Capecitabine Plus Oxaliplatin) Followed by Capecitabine Maintenance or Clinical Observation
Guk Jin LEE ; Hyunho KIM ; Sung Shim CHO ; Hyung Soon PARK ; Ho Jung AN ; In Sook WOO ; Jae Ho BYUN ; Ji Hyung HONG ; Yoon Ho KO ; Der Sheng SUN ; Hye Sung WON ; Jong Youl JIN ; Ji Chan PARK ; In-Ho KIM ; Sang Young ROH ; Byoung Yong SHIM
Journal of Gastric Cancer 2023;23(2):315-327
Purpose:
Oxaliplatin, a component of the capecitabine plus oxaliplatin (XELOX) regimen, has a more favorable toxicity profile than cisplatin in patients with advanced gastric cancer (GC). However, oxaliplatin can induce sensory neuropathy and cumulative, dose-related toxicities. Thus, the capecitabine maintenance regimen may achieve the maximum treatment effect while reducing the cumulative neurotoxicity of oxaliplatin. This study aimed to compare the survival of patients with advanced GC between capecitabine maintenance and observation after 1st line XELOX chemotherapy.
Materials and Methods:
Sixty-three patients treated with six cycles of XELOX for advanced GC in six hospitals of the Catholic University of Korea were randomized 1:1 to receive capecitabine maintenance or observation. The primary endpoint was progression-free survival (PFS), analyzed using a two-sided log-rank test stratified at a 5% significance level.
Results:
Between 2015 and 2020, 32 and 31 patients were randomized into the maintenance and observation groups, respectively. After randomization, the median number of capecitabine maintenance cycles was 6. The PFS was significantly higher in the maintenance group than the observation group (6.3 vs. 4.1 months, P=0.010). Overall survival was not significantly different between the 2 groups (18.2 vs. 16.5 months, P=0.624). Toxicities, such as hand-foot syndrome, were reported in some maintenance group patients. Maintenance treatment was a significant factor associated with PFS in multivariate analysis (hazard ratio, 0.472; 95% confidence interval, 0.250–0.890; P=0.020).
Conclusions
After 6 cycles of XELOX chemotherapy, capecitabine maintenance significantly prolonged PFS compared with observation, and toxicity was manageable. Maintenance treatment was a significant prognostic factor associated with PFS.
6.Antenatal Magnesium Sulfate Is Not Associated With Improved Long-Term Neurodevelopment and Growth in Very Low Birth Weight Infants
Ga Won JEON ; So Yoon AHN ; Su Min KIM ; Misun YANG ; Se In SUNG ; Ji-Hee SUNG ; Soo-young OH ; Cheong-Rae ROH ; Suk-Joo CHOI ; Yun Sil CHANG
Journal of Korean Medical Science 2023;38(44):e350-
Background:
Though antenatal magnesium sulfate (MgSO4 ) is widely used for fetal neuroprotection, suspicions about the long-term neuroprotection of antenatal MgSO4 have been raised.
Methods:
We investigated short- and long-term outcomes of antenatal MgSO4 use for 468 infants weighing < 1,500 g with a gestational age of 24–31 weeks.
Results:
Short-term morbidities and the risk of developmental delay, hearing loss, and cerebral palsy at a corrected age of 18–24 months and 3 years of age did not decrease in the MgSO4 group (infants who were exposed to MgSO4 for any purpose) or neuroprotection group (infants who were exposed to MgSO4 for fetal neuroprotection) compared with the control group (infants who were not exposed to MgSO4 ). The z-scores of weight, height, and head circumference did not increase in the MgSO4 group or neuroprotection group compared with the control group.
Conclusion
Antenatal MgSO4 including MgSO4 for neuroprotection did not have beneficial effects on long-term neurodevelopmental and growth outcomes.
7.Isolation and characterization of cancer-associated fibroblasts in the tumor microenvironment of hepatocellular carcinoma
Kyoungdo MUN ; Jiwon HAN ; Pureun ROH ; Jonggeun PARK ; Gahee KIM ; Wonhee HUR ; Jeongwon JANG ; Jongyoung CHOI ; Seungkew YOON ; Youngkyoung YOU ; Hojoong CHOI ; Pilsoo SUNG
Journal of Liver Cancer 2023;23(2):341-349
Background:
/Aim: Cancer-associated fibroblasts (CAFs) play an immunosuppressive role in the tumor microenvironment (TME) of human cancers; however, their characteristics and role in hepatocellular carcinoma (HCC) remain to be elucidated.
Methods:
Nine tumor and surrounding liver tissue samples from patients with HCC who underwent surgery were used to isolate patient-derived CAFs. Cell morphology was observed using an optical microscope after culture, and cell phenotypes were evaluated using flow cytometry and immunoblotting. Cytokines secreted by CAFs into culture medium were quantified using a multiplex cytokine assay.
Results:
CAFs were abundant in the TME of HCC and were adjacent to immune cells. After culture, the CAFs and non-tumor fibroblasts exhibited spindle shapes. We observed a robust expression of alpha-smooth muscle actin and fibroblast activation protein in CAFs, whereas alpha-fetoprotein, epithelial cell adhesion molecule, platelet/endothelial cell adhesion molecule-1, and E-cadherin were not expressed in CAFs. Furthermore, CAFs showed high secretion of various cytokines, namely C-X-C motif chemokine ligand 12, interleukin (IL)-6, IL-8, and C-C motif chemokine ligand 2.
Conclusions
CAFs are abundant in the TME of HCC and play a crucial role in tumor progression. These fibroblasts secrete cytokines that promote tumor growth and metastasis.
8.The role of postoperative neutrophil-to-lymphocyte ratio as a predictor of postoperative major complications following total gastrectomy for gastric cancer
Jae Seung KWAK ; Sung Gon KIM ; Sang Eok LEE ; Won Jun CHOI ; Dae Sung YOON ; In Seok CHOI ; Ju Ik MOON ; Nak Song SUNG ; Seong Uk KWON ; In Eui BAE ; Seung Jae LEE ; Seung Jae ROH
Annals of Surgical Treatment and Research 2022;103(3):153-159
Purpose:
This study was performed to investigate the role of the perioperative neutrophil-to-lymphocyte ratio (NLR) as an early predictor of major postoperative complications after total gastrectomy for gastric cancer.
Methods:
This single-center, retrospective study reviewed consecutive patients with gastric cancer who underwent total gastrectomy at a single institution from March 2009 to March 2021. The postoperative complications were graded according to the Clavien-Dindo classification. We analyzed the patient demographics and surgical outcomes according to the grade of postoperative complications in the major complications group (≥grade III) and the no major complications group (
9.Auranofin attenuates hepatic steatosis and fibrosis in nonalcoholic fatty liver disease via NRF2 and NF- κB signaling pathways
Seung Min LEE ; Dong Hee KOH ; Dae Won JUN ; Yoon Jin ROH ; Hyeon Tae KANG ; Ju Hee OH ; Hyun Sung KIM
Clinical and Molecular Hepatology 2022;28(4):827-840
Background/Aims:
We aim to evaluate the effects of auranofin, a known antioxidant, on hepatic steatosis, inflammation, and fibrosis, contributing to non-alcoholic steatohepatitis (NASH) development in vivo and in vitro.
Methods:
Transcriptome analysis of LX-2 cells was that expression patterns of genes changed by auranofin, and their related pathways were estimated. We used the gene set enrichment analysis (GSEA) program to determine the pathway involved in overall genetic change. In vitro, LX-2 and HepG2 cells were treated with transforming growth factor (TGF)-β1 and palmitic acid (PA), respectively, and the antifibrotic and antiadipogenic effect function of auranofin was evaluated.
Results:
Transcriptome analysis revealed that auranofin decreased the expression of 15 genes, including thrombospondin 1, endothelin 1 (ET-1), fibronectin 1, and LOX. The molecular functions of these genes are involved in collagen binding. GSEA of the overall gene expression pattern revealed that many genes increased in the reactive oxygen species pathway and decreased in the inflammatory response. Auranofin decreased nuclear factor kappa B (NF-κB) and IκBα in TGF-β1-induced LX-2 cells, thereby reducing ET-1 and fibrosis. Furthermore, increased pNRF2 in PA-induced HepG2 cells led to increased antioxidant marker expression and decreased lipid accumulation. In the bile duct ligation model mice, auranofin reduced the fibrosis area and increased the survival rate. Auranofin reduced liver fibrosis and lipid accumulation in NASH model mice fed on a Western diet.
Conclusions
Auranofin inhibits lipogenesis and fibrosis formation and is a proposed candidate for NASH treatment.
10.Optimal indication of single-incision laparoscopic cholecystectomy using Konyang Standard Method in benign gallbladder diseases
Seung Jae LEE ; In Seok CHOI ; Ju Ik MOON ; Dae Sung YOON ; Won Jun CHOI ; Sang Eok LEE ; Nak Song SUNG ; Seong Uk KWON ; In Eui BAE ; Seung Jae ROH ; Sung Gon KIM
Journal of Minimally Invasive Surgery 2022;25(3):97-105
Purpose:
The optimal indications for single-incision laparoscopic cholecystectomy (SILC) have not yet been established.
Methods:
This single-center retrospective study included consecutive patients who underwent SILC between April 2010 and June 2020. Dif f icult surger y (DS) (conversion to multiport or open cholecystectomy, adjacent organ injury, operation time of ≥90 minutes, or estimated blood loss of ≥100 mL) and poor postoperative outcome (PPO) (postoperative hospital stay ≥ 7 days or Clavien-Dindo grade ≥ II postoperative complications) were def ined to comprehensively evaluate surgical diff iculty and postoperative outcomes, respectively.
Results:
Of 1,405 patients (mean age, 51.2 years; 802 female [57.1%]), 427 (grade I, n = 358; grade II/III, n = 69) underwent SILC for acute cholecystitis (AC), 34 (2.4%) needed conversion to multiport (n = 33) or open cholecystectomy (n = 1), 7 (0.5%) had adjacent organ injury during surgery, and 49 (3.5%) developed postoperative complications. Of the patients, 89 and 52 had DS and PPO, respectively. In the multivariate analysis, grade I AC, grade II/III AC, and body mass index of ≥30 kg/m 2 were significant predictors of DS.Age of ≥70 years and DS were significant predictors of PPO. In a subgroup analysis of patients with AC, DS (9.5% vs. 27.5%, p < 0.001) and PPO (5.0% vs. 15.9%, p = 0.001) were more frequent in patients with grade II/III AC than in those with grade I AC.
Conclusion
SILC is not recommended in patients with grade II/III AC and should be carefully performed by experienced and well-trained surgeons.

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