1.Male preference for TERT alterations and HBV integration in young-age HBV-related HCC: implications for sex disparity
Jin Seoub KIM ; Hye Seon KIM ; Kwon Yong TAK ; Ji Won HAN ; Heechul NAM ; Pil Soo SUNG ; Sung Won LEE ; Jung Hyun KWON ; Si Hyun BAE ; Jong Young CHOI ; Seung Kew YOON ; Jeong Won JANG
Clinical and Molecular Hepatology 2025;31(2):509-524
Background/Aims:
Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC.
Methods:
We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data.
Results:
Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data.
Conclusions
Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.
2.Male preference for TERT alterations and HBV integration in young-age HBV-related HCC: implications for sex disparity
Jin Seoub KIM ; Hye Seon KIM ; Kwon Yong TAK ; Ji Won HAN ; Heechul NAM ; Pil Soo SUNG ; Sung Won LEE ; Jung Hyun KWON ; Si Hyun BAE ; Jong Young CHOI ; Seung Kew YOON ; Jeong Won JANG
Clinical and Molecular Hepatology 2025;31(2):509-524
Background/Aims:
Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC.
Methods:
We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data.
Results:
Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data.
Conclusions
Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.
3.Male preference for TERT alterations and HBV integration in young-age HBV-related HCC: implications for sex disparity
Jin Seoub KIM ; Hye Seon KIM ; Kwon Yong TAK ; Ji Won HAN ; Heechul NAM ; Pil Soo SUNG ; Sung Won LEE ; Jung Hyun KWON ; Si Hyun BAE ; Jong Young CHOI ; Seung Kew YOON ; Jeong Won JANG
Clinical and Molecular Hepatology 2025;31(2):509-524
Background/Aims:
Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC.
Methods:
We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data.
Results:
Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data.
Conclusions
Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.
4.Neuroblastoma: A 2020 Survey Conducted by the Korean Association of Pediatric Surgeons
Hee-Beom YANG ; Soo Min AHN ; Min Jeng CHO ; Yong-Hoon CHO ; Soo Jin Na CHOI ; Yoon Mi CHOI ; Jae Hee CHUNG ; Seok Joo HAN ; In Geol HO ; Jeong HONG ; Kyong IHN ; Yeon Jun JEONG ; Eunyoung JUNG ; Dae Youn KIM ; Hae-Young KIM ; Ki Hoon KIM ; Seong Chul KIM ; Soo-Hong KIM ; Eun-Jung KOO ; Hyun Hee KWON ; Yong Jae KWON ; Nam-Hyuk LEE ; Ju Yeon LEE ; Sanghoon LEE ; Jung-Man NAMGOONG ; Chaeyoun OH ; Jung-Tak OH ; Jin Young PARK ; Junbeom PARK ; Jeong-Meen SEO ; Jae Ho SHIN ; Hyun Beak SHIN ; Joohyun SIM ; Jiyoung SUL ; Joon Kee YOUN ; Hyun-Young KIM
Advances in Pediatric Surgery 2025;31(2):66-76
Purpose:
To report a nationwide survey on neuroblastoma conducted by the Korean Association of Pediatric Surgeons (KAPS) in 2020.
Methods:
The clinical data of pediatric patients diagnosed with and treated for neuroblastoma from 2005 to 2019 in 19 hospitals of KAPS members were collected. Survival and prognostic factor analyses were performed using the log rank test and Cox proportional hazard analysis. A p-value <0.05 was considered significant.
Results:
A total of 669 patients with neuroblastoma were registered for the study. The results were presented and discussed at the 36th annual meeting of the KAPS, which was held in Seoul on August 21, 2020.
Conclusion
This study provides information on patient demographics, prognostic outcomes, and comprehensive treatment outcomes for neuroblastoma. The study is expected to be an important reference for improving pediatric surgeons’ understanding and treatment of neuroblastoma.
5.A Comparative Study of Three National Surveys on Biliary Atresia by the Korean Association of Pediatric Surgeons
Yeon Jun JEONG ; Dayoung KO ; Hyunhee KWON ; Ki Hoon KIM ; Dae Yeon KIM ; Soo-Hong KIM ; Wontae KIM ; Hae-Young KIM ; Hyun Young KIM ; Seong Chul KIM ; Younghyun NA ; Jung-Man NAMGOONG ; So Hyun NAM ; Junbeom PARK ; Jinyoung PARK ; Tae-Jun PARK ; Jeong-Meen SEO ; Ji-Young SUL ; Joonhyuk SON ; Hyun Beak SHIN ; Joohyun SIM ; Soo Min AHN ; Hee Beom YANG ; Jung-Tak OH ; Chaeyoun OH ; Joong Kee YOUN ; Sanghoon LEE ; Ju Yeon LEE ; Kyong IHN ; Hye Kyung CHANG ; Eunyoung JUNG ; Jae Hee CHUNG ; Yu Jeong CHO ; Yun Mee CHOE ; Soo Jin Na CHOI ; Seok Joo HAN ; In Geol HO ; Ji-Won HAN
Advances in Pediatric Surgery 2025;31(2):47-58
Purpose:
Biliary atresia (BA) is a rare but progressive cholangiopathy and the leading cause of pediatric liver transplantation worldwide. The Korean Association of Pediatric Surgeons (KAPS) has conducted three national surveys (2001, 2011, and 2023) to assess long-term trends in the diagnosis, treatment, and outcomes of BA. This study provides a comparative analysis of the 2nd and 3rd national surveys, with reference to selected findings from the 1st survey.
Methods:
This study included 453 patients from the 3rd national survey (2011–2021) and 435 patients from the 2nd survey (2001–2010), all of whom underwent Kasai portoenterostomy. Data were collected via electronic case report forms from pediatric surgical centers nationwide. Comparisons were made regarding demographics, clinical features, diagnostic patterns, operative details, follow-up outcomes, and survival. Kaplan–Meier analysis was used to evaluate long-term survival.
Results:
The mean number of BA patients per year remained stable between surveys (43.5 in the 2nd, 41.18 in the 3rd), though centralization of care increased, with 61.5% of cases managed by two major institutions in the 3rd survey. The median age at surgery decreased, and the use of preoperative imaging (especially magnetic resonance cholangiopancreatography) increased. The 10-year native liver survival rate declined from 59.8% to 53.7%, while overall 10-year survival improved slightly (92.9% to 93.2%). Postoperative complications, such as cholangitis and liver failure, persisted but were better categorized. The 3rd survey also reported improved mortality (4.9%) and reduced follow-up loss (11.5%) compared to the 2nd survey.
Conclusion
While overall survival after Kasai operation has remained high and even improved, native liver survival has slightly declined. The findings reflect earlier diagnosis, more consistent diagnostic imaging, and increasing centralization of care. These trends underscore the importance of long-term nationwide data collection in guiding future strategies for BA management in Korea.
6.Pyogenic granuloma of the hard palate leading to alveolar cleft: a case report
Woo Jin SONG ; Hyun Beom CHOI ; Min Sung TAK
Archives of Craniofacial Surgery 2024;25(3):150-154
This case report describes a rare occurrence of pyogenic granuloma (PG) in the hard palate deviating from its typical gingival location that led to the formation of an alveolar cleft. The aggressive growth pattern of the lesion, with atypical progression from a pedunculated nodule to an alveolar cleft, raised concern. The diagnosis was based on magnetic resonance imaging and computed tomography findings, which revealed a tadpole-shaped lesion originating from the midline hard palate. The differential diagnosis included a minor salivary gland tumor. Surgical excision was performed under general anesthesia and resulted in a mucosal defect without nasolabial fistula formation or bone exposure. The palatal defect was packed with oxidized regenerated cellulose and closed with Vicryl Rapide sutures, both of which contributed to the patient’s successful outcomes. Our comprehensive approach, extending across the stages of surgical planning, execution, and postoperative care, demonstrated the advantages of a multidisciplinary strategy for the accurate diagnosis and effective treatment of palatal PGs. This report makes a meaningful contribution to the existing literature on common oral lesions by emphasizing the importance of a broad differential diagnosis and a systematic approach to oral pathologies. It also raises clinical awareness of PGs with atypical presentations and the diagnostic challenge that they pose.
7.National Survey of Gastroschisis and Omphalocele by Korean Association of Pediatric Surgeons
Yeon Jun JEONG ; Dayoung KO ; Eun-Jung KOO ; Hyunhee KWON ; Dae Yeon KIM ; Soo-Hong KIM ; Wontae KIM ; Hae-Young KIM ; Hyun Young KIM ; Seong Chul KIM ; Younghyun NA ; Jung-Man NAMGOONG ; So Hyun NAM ; Sungjoo PARK ; Junbeom PARK ; Jinyoung PARK ; Tae-Jun PARK ; Jeong-Meen SEO ; Ji-Young SUL ; Joonhyuk SON ; Hyun Beak SHIN ; Joohyun SIM ; Jung-Tak OH ; Chaeyoun OH ; Joong Kee YOUN ; Sanghoon LEE ; Ju Yeon LEE ; Cheolgu LEE ; Kyong IHN ; Eunyoung JUNG ; Jae Hee CHUNG ; Yong-Hoon CHO ; Yun Mee CHOE ; Soo Jin Na CHOI ; Seok Joo HAN ; In Geol HO
Advances in Pediatric Surgery 2024;30(2):39-51
Purpose:
This study provides insights into the prevalence at birth, clinical characteristics, and outcomes of gastroschisis and omphalocele in Korea over the past decade, addressing the lack of localized data despite advanced healthcare capabilities.
Methods:
The study retrospectively analyzed data from 20 pediatric surgical centers in Korea from January 2012 to December 2021, including 269 patients diagnosed with gastroschisis or omphalocele. Data variables included gender, gestational age, birth weight, associated anomalies, type of defect, surgical interventions, and outcomes.
Results:
The study covered 269 patients, with 80 gastroschisis and 189 omphalocele cases. Gastroschisis prevalence at birth remained stable at 2.15 per 100,000 live births, while omphalocele increased to 5.08 per 100,000. Both conditions had similar gender ratios (0.95). Gastroschisis patients had lower birth weights (2,463.90±505.50 g) and smaller head circumferences (31.97±1.86 cm) compared to omphalocele patients (2,757.65±761.24 g, 32.78±2.64 cm). Omphalocele cases had more associated anomalies, especially cardiovascular issues. Prenatal diagnosis rates were high: 93.7% for gastroschisis and 86.4% for omphalocele. About 96.3% of gastroschisis and 84.1% of omphalocele patients were born in their treatment hospitals. Gastroschisis patients underwent surgery sooner (average 3.5 days) and started feeding later (16.5 days) than omphalocele patients (average 56.5 days to surgery, 6.6 days to start feeding). Hospital stays and follow-up durations were similar, averaging around 782.6 days for gastroschisis and 800.3 days for omphalocele patients. Survival rates were 89.7% for gastroschisis and 87.1% for omphalocele.
Conclusion
The study highlights the need for early diagnosis, centralized care, and specialized surgical approaches to optimize outcomes for gastroschisis and omphalocele patients in Korea. Enhanced prenatal screening and surgical protocols are recommended to improve these patients' prognosis.
8.Computational Analysis of miR-140 and miR-135as Potential Targets to Develop Combinatorial Therapeutics for Degenerative Tendinopathy
Vivek Kumar MORYA ; Ho-Won LEE ; Chang-Wook PARK ; Chang-Won PARK ; Jin Tak HYUN ; Kyu-Cheol NOH
Clinics in Orthopedic Surgery 2023;15(3):463-476
Background:
Degenerative tendinopathy, a condition causing movement restriction due to high pain, highly impacts productivity and quality of life. The healing process is a complex phenomenon and involves a series of intra-cellular and inter-cellular processes. Proliferation and differentiation of the tenocyte is a major and essential process to heal degenerative tendinopathy. The recent development in microRNA (miRNA)-mediated reprogramming of the cellular function through specific pathways opened door for the development of new regenerative therapeutics. Based on information about gene expression and regulation of tendon injury and healing, we attempted to evaluate the combinatorial effect of selected miRNAs for better healing of degenerative tendinopathy.
Methods:
The present study was designed to evaluate the combinatorial effect of two miRNAs (has-miR-140 and has-miR-135) in the healing process of the tendon. Publicly available information/data were retrieved from appropriate platforms such as PubMed.Only molecular data, directly associated with tendinopathies, including genes/proteins and miRNAs, were used in this study. The miRNAs involved in tendinopathy were analyzed by a Bioinformatics tools (e.g., TargetScan, miRDB, and the RNA22v2). Interactive involvement of the miRNAs with key proteins involved in tendinopathy was predicted by the Insilco approach.
Results:
Based on information available in the public domain, tendon healing-associated miRNAs were predicted to explore their therapeutic potentials. Based on computation analysis, focusing on the potential regulatory effect on tendon healing, the miR-135 and miR-140 were selected for this study. These miRNAs were found as key players in tendon healing through Rho-associated coiled-coil containing protein kinase 1 (ROCK1), IGF-1/PI3K/Akt, PIN, and Wnt signaling pathways. It was also predicted that these miRNAs may reprogram the cells to induce proliferation and differentiation activity. Many miRNAs are likely to regulate genes important for the tendinopathy healing process, and the result of this study allows an approach for miRNA-mediated regeneration of the tenocyte for tendon healing. Based on computational analysis, the role of these miRNAs in different pathways was established, and the results provided insights into the combinatorial approach of miRNA-mediated cell reprogramming.
Conclusions
In this study, the association between miRNAs and the disease was evaluated to correlate the tendinopathy genes and the relevant role of different miRNAs in their regulation. Through this study, it was established that the synergistic effect of more than one miRNA on directed reprogramming of the cell could be helpful in the regeneration of damaged tissue. It is anticipated that this study will be helpful for the design of miRNA cocktails for the orchestration of cellular reprogramming events.
9.Efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for hepatitis C in Korea: a Phase 3b study
Jeong HEO ; Yoon Jun KIM ; Sung Wook LEE ; Youn-Jae LEE ; Ki Tae YOON ; Kwan Soo BYUN ; Yong Jin JUNG ; Won Young TAK ; Sook-Hyang JEONG ; Kyung Min KWON ; Vithika SURI ; Peiwen WU ; Byoung Kuk JANG ; Byung Seok LEE ; Ju-Yeon CHO ; Jeong Won JANG ; Soo Hyun YANG ; Seung Woon PAIK ; Hyung Joon KIM ; Jung Hyun KWON ; Neung Hwa PARK ; Ju Hyun KIM ; In Hee KIM ; Sang Hoon AHN ; Young-Suk LIM
The Korean Journal of Internal Medicine 2023;38(4):504-513
Despite the availability of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection in Korea, need remains for pangenotypic regimens that can be used in the presence of hepatic impairment, comorbidities, or prior treatment failure. We investigated the efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for 12 weeks in HCV-infected Korean adults. Methods: This Phase 3b, multicenter, open-label study included 2 cohorts. In Cohort 1, participants with HCV genotype 1 or 2 and who were treatment-naive or treatment-experienced with interferon-based treatments, received sofosbuvir–velpatasvir 400/100 mg/day. In Cohort 2, HCV genotype 1 infected individuals who previously received an NS5A inhibitor-containing regimen ≥ 4 weeks received sofosbuvir–velpatasvir–voxilaprevir 400/100/100 mg/day. Decompensated cirrhosis was an exclusion criterion. The primary endpoint was SVR12, defined as HCV RNA < 15 IU/mL 12 weeks following treatment. Results: Of 53 participants receiving sofosbuvir–velpatasvir, 52 (98.1%) achieved SVR12. The single participant who did not achieve SVR12 experienced an asymptomatic Grade 3 ASL/ALT elevation on day 15 and discontinued treatment. The event resolved without intervention. All 33 participants (100%) treated with sofosbuvir–velpatasvir–voxilaprevir achieved SVR 12. Overall, sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir were safe and well tolerated. Three participants (5.6%) in Cohort 1 and 1 participant (3.0%) in Cohort 2 had serious adverse events, but none were considered treatment-related. No deaths or grade 4 laboratory abnormalities were reported. Conclusions: Treatment with sofosbuvir–velpatasvir or sofosbuvir–velpatasvir–voxilaprevir was safe and resulted in high SVR12 rates in Korean HCV patients.

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