1.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.
2.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.
3.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.
4.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.
5.Learning curve for single-port robot-assisted colectomy
Moon Suk CHOI ; Seong Hyeon YUN ; Sung Chul LEE ; Jung Kyong SHIN ; Yoon Ah PARK ; Jungwook HUH ; Yong Beom CHO ; Hee Cheol KIM ; Woo Yong LEE
Annals of Coloproctology 2024;40(1):44-51
Purpose:
Since the introduction of robotic surgery, robots for colorectal cancer have replaced laparoscopic surgery, and a single-port robot (SPR) platform has been launched and is being used to treat patients. We analyzed the learning curve and initial complications of using an SPR platform in colorectal cancer surgery.
Methods:
We reviewed 39 patients who underwent SPR colectomy from April to October 2019. All surgeries were performed by the same surgeon using an SPR device. A learning curve was generated using the cumulative sum methodology to assess changes in total operation time, docking time, and surgeon console time. We grouped the patients into 3 groups according to the time period: the first 11 were phase 1, the next 11 were phase 2, and the last 17 were phase 3.
Results:
The mean age of the patients was 61.28±13.03 years, and they had a mean body mass index of 23.79±2.86 kg/m2. Among the patients, 23 (59.0%) were male, and 16 (41.0%) were female. The average operation time was 186.59±51.30 minutes, the average surgeon console time was 95.49±35.33 minutes, and the average docking time (time from skin incision to robot docking) was 14.87±10.38 minutes. The surgeon console time differed significantly among the different phases (P<0.001). Complications occurred in 8 patients: 2 ileus, 2 postoperation hemoglobin changes, 3 urinary retentions, and 1 complicated fluid collection.
Conclusion
In our experience, the learning curve for SPR colectomy was achieved after the 18th case.
6.Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE)
Nam Hoon KIM ; Juneyoung LEE ; Suk CHON ; Jae Myung YU ; In-Kyung JEONG ; Soo LIM ; Won Jun KIM ; Keeho SONG ; Ho Chan CHO ; Hea Min YU ; Kyoung-Ah KIM ; Sang Soo KIM ; Soon Hee LEE ; Chong Hwa KIM ; Soo Heon KWAK ; Yong‐ho LEE ; Choon Hee CHUNG ; Sihoon LEE ; Heung Yong JIN ; Jae Hyuk LEE ; Gwanpyo KOH ; Sang-Yong KIM ; Jaetaek KIM ; Ju Hee LEE ; Tae Nyun KIM ; Hyun Jeong JEON ; Ji Hyun LEE ; Jae-Han JEON ; Hye Jin YOO ; Hee Kyung KIM ; Hyeong-Kyu PARK ; Il Seong NAM-GOONG ; Seongbin HONG ; Chul Woo AHN ; Ji Hee YU ; Jong Heon PARK ; Keun-Gyu PARK ; Chan Ho PARK ; Kyong Hye JOUNG ; Ohk-Hyun RYU ; Keun Yong PARK ; Eun-Gyoung HONG ; Bong-Soo CHA ; Kyu Chang WON ; Yoon-Sok CHUNG ; Sin Gon KIM
Endocrinology and Metabolism 2024;39(5):722-731
Background:
Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined.
Methods:
This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months.
Conclusion
This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.
7.Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Overview and Summary 2024
Young Joo PARK ; Eun Kyung LEE ; Young Shin SONG ; Bon Seok KOO ; Hyungju KWON ; Keunyoung KIM ; Mijin KIM ; Bo Hyun KIM ; Won Gu KIM ; Won Bae KIM ; Won Woong KIM ; Jung-Han KIM ; Hee Kyung KIM ; Hee Young NA ; Shin Je MOON ; Jung-Eun MOON ; Sohyun PARK ; Jun-Ook PARK ; Ji-In BANG ; Kyorim BACK ; Youngduk SEO ; Dong Yeob SHIN ; Su-Jin SHIN ; Hwa Young AHN ; So Won OH ; Seung Hoon WOO ; Ho-Ryun WON ; Chang Hwan RYU ; Jee Hee YOON ; Ka Hee YI ; Min Kyoung LEE ; Sang-Woo LEE ; Seung Eun LEE ; Sihoon LEE ; Young Ah LEE ; Joon-Hyop LEE ; Ji Ye LEE ; Jieun LEE ; Cho Rok LEE ; Dong-Jun LIM ; Jae-Yol LIM ; Yun Kyung JEON ; Kyong Yeun JUNG ; Ari CHONG ; Yun Jae CHUNG ; Chan Kwon JUNG ; Kwanhoon JO ; Yoon Young CHO ; A Ram HONG ; Chae Moon HONG ; Ho-Cheol KANG ; Sun Wook KIM ; Woong Youn CHUNG ; Do Joon PARK ; Dong Gyu NA ;
International Journal of Thyroidology 2024;17(1):1-20
Differentiated thyroid cancer demonstrates a wide range of clinical presentations, from very indolent cases to those with an aggressive prognosis. Therefore, diagnosing and treating each cancer appropriately based on its risk status is important. The Korean Thyroid Association (KTA) has provided and amended the clinical guidelines for thyroid cancer management since 2007. The main changes in this revised 2024 guideline include 1) individualization of surgical extent according to pathological tests and clinical findings, 2) application of active surveillance in low-risk papillary thyroid microcarcinoma, 3) indications for minimally invasive surgery, 4) adoption of World Health Organization pathological diagnostic criteria and definition of terminology in Korean, 5) update on literature evidence of recurrence risk for initial risk stratification, 6) addition of the role of molecular testing, 7) addition of definition of initial risk stratification and targeting thyroid stimulating hormone (TSH) concentrations according to ongoing risk stratification (ORS), 8) addition of treatment of perioperative hypoparathyroidism, 9) update on systemic chemotherapy, and 10) addition of treatment for pediatric patients with thyroid cancer.
8.A Causality Assessment Framework for COVID-19 Vaccines and Adverse Events at the COVID-19 Vaccine Safety Research Center
Seyoung KIM ; Jeong Ah KIM ; Hyesook PARK ; Sohee PARK ; Sanghoon OH ; Seung Eun JUNG ; Hyoung-Shik SHIN ; Jong Koo LEE ; Hee Chul HAN ; Jun Hee WOO ; Byung-Joo PARK ; Nam-Kyong CHOI ; Dong-Hyun KIM
Journal of Korean Medical Science 2024;39(26):e220-
During the coronavirus disease 2019 (COVID-19) pandemic, conclusively evaluating possible associations between COVID-19 vaccines and potential adverse events was of critical importance. The National Academy of Medicine of Korea established the COVID-19 Vaccine Safety Research Center (CoVaSC) with support from the Korea Disease Control and Prevention Agency to investigate the scientific relationship between COVID-19 vaccines and suspected adverse events. Although determining whether the COVID-19 vaccine was responsible for any suspected adverse event necessitated a systematic approach, traditional causal inference theories, such as Hill's criteria, encountered certain limitations and criticisms. To facilitate a systematic and evidence-based evaluation, the United States Institute of Medicine, at the request of the Centers for Disease Control and Prevention, offered a detailed causality assessment framework in 2012, which was updated in the recent report by the National Academies of Sciences, Engineering, and Medicine (NASEM) in 2024.This framework, based on a weight-of-evidence approach, allows the independent evaluation of both epidemiological and mechanistic evidence, culminating in a comprehensive conclusion about causality. Epidemiological evidence derived from population studies is categorized into four levels—high, moderate, limited, or insufficient—while mechanistic evidence, primarily from biological and clinical studies in animals and individuals, is classified as strong, intermediate, weak, or lacking. The committee then synthesizes these two types of evidence to draw a conclusion about the causal relationship, which can be described as “convincingly supports” (“evidence established” in the 2024 NASEM report), “favors acceptance,” “favors rejection,” or “inadequate to accept or reject.” The CoVaSC has established an independent committee to conduct causality assessments using the weightof-evidence framework, specifically for evaluating the causality of adverse events associated with COVID-19 vaccines. The aim of this study is to provide an overview of the weight-ofevidence framework and to detail the considerations involved in its practical application in the CoVaSC.
9.Reported Adverse Events and Associated Factors in Korean Coronavirus Disease 2019 Vaccinations
Hyunjin PARK ; Eunsun LIM ; Seunghee JUN ; Hyelim LEE ; Hye Ah LEE ; Hyesook PARK ; Nam-Kyong CHOI ; Bomi PARK
Journal of Korean Medical Science 2024;39(42):e274-
Background:
Despite their effectiveness, coronavirus disease 2019 (COVID-19) vaccines have been associated with adverse effects, underscoring the importance of continuous surveillance to ensure vaccine safety and effective management of public health. Herein, the characteristics and risk factors of vaccine-related adverse events (AEs) were identified to gain an in-depth understanding of vaccine safety by investigating the impact of the vaccination dose on changes in post-vaccination AEs.
Methods:
Herein, a linked database of COVID-19 vaccination records from the Korea Disease Control and Prevention Agency, AE reports from the COVID-19 Vaccination Management System, and healthcare claims from the National Health Insurance Service, targeting ≥ 5-year-old individuals, was utilized (study duration = February 26, 2021, to January 31, 2023).The frequency and severity of reported post-vaccination AEs were evaluated. Furthermore, we specifically explored AEs in relation to the cumulative dosage of vaccines administered while evaluating associated risk factors.
Results:
During the observation period, 42,804,523 individuals completed the COVID-19 vaccination series, with 365,900 reporting AEs, with headache, muscle pain, and fever being the most frequently reported. Notably, the AE reports were approximately twice as high for women than for men, which was further exacerbated following both doses. Analysis by age group revealed that AE reports were lower among children, adolescents, and older adults than in the middleaged cohort (age = 50–64 years), with higher reports observed for 18–49-year-old individuals.Additionally, a higher risk of reporting was identified among individuals with lower socioeconomic status compared with those of middle socioeconomic status. Excluding dementia, the risk of reporting AEs was high in individuals with underlying diseases compared with those without, for instance, the risk of reporting AEs following two-dose vaccinations was approximately twice as high in individuals with chronic obstructive pulmonary disease and asthma.
Conclusion
These findings indicate that women, younger people, those with a lower socioeconomic status, and those with underlying health conditions reported a higher incidence of AEs following COVID-19 vaccinations. This emphasizes the need for continued monitoring to ensure safe vaccination and address vaccine-related anxiety and fear, especially within the aforementioned groups.
10.Clinical outcomes of neoadjuvant chemoradiotherapy followed by total mesorectal excision in locally advanced rectal cancer with mesorectal fascia involvement
Jeong Ha LEE ; Nalee KIM ; Jeong Il YU ; Gyu Sang YOO ; Hee Chul PARK ; Woo-Yong LEE ; Seong Hyeon YUN ; Hee Cheol KIM ; Yong Beom CHO ; Jung Wook HUH ; Yoon Ah PARK ; Jung Kyong SHIN ; Joon Oh PARK ; Seung Tae KIM ; Young Suk PARK ; Jeeyun LEE ; Won Ki KANG
Radiation Oncology Journal 2024;42(2):130-138
Purpose:
For the treatment of locally advanced rectal cancer (LARC), research on primary lesions with mesorectal fascia (MRF) involvement is lacking. This study analyzed the clinical outcomes and efficacy of dose-escalated neoadjuvant concurrent chemoradiotherapy (NCRT) to patients with LARC involving MRF.
Materials and Methods:
We retrospectively reviewed 301 patients who were diagnosed with LARC involving MRF and underwent NCRT followed by total mesorectal excision (TME). Patients who received radiotherapy (RT) doses of ≤50.4 Gy were defined as the non-boost group, while ≥54.0 Gy as the boost group. Pathological tumor response and survival outcomes, including intrapelvic recurrence-free survival (IPRFS), distant metastases-free survival (DMFS) and overall survival (OS), were analyzed.
Results:
A total of 269 patients (89.4%) achieved a negative pathological circumferential resection margin and 104 (34.6%) had good pathological tumor regression grades. With a median follow-up of 32.4 months, IPRFS, DMFS, and OS rates at 5-years were 88.6%, 78.0%, and 91.2%, respectively. In the subgroup analysis by RT dose, the boost group included more advanced clinical stages of patients. For the non-boost group and boost group, 5-year IPRFS rates were 90.3% and 87.0% (p = 0.242), 5-year DMFS rates were 82.0% and 71.3% (p = 0.105), and 5-year OS rates were 93.0% and 80.6% (p = 0.439), respectively. Treatment related toxicity was comparable between the two groups (p = 0.211).
Conclusion
Although this retrospective study failed to confirm the efficacy of dose-escalated NCRT, favorable IPRFS and pathological complete response was achieved with NCRT followed by TME. Further studies combining patient customized RT dose with systemic therapies are needed.

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