1.Shank3 Overexpression Leads to Cardiac Dysfunction in Mice by Disrupting Calcium Homeostasis in Cardiomyocytes
Tae Hee KO ; Yoonhee KIM ; Chunmei JIN ; Byeongil YU ; Minju LEE ; Phuong Kim LUONG ; Tran Nguyet TRINH ; Yeji YANG ; Hyojin KANG ; Yinhua ZHANG ; Ruiying MA ; Kwangmin YOO ; Jungmin CHOI ; Jin Young KIM ; Sun-Hee WOO ; Kihoon HAN ; Jong-Il CHOI
Korean Circulation Journal 2025;55(2):100-117
Background and Objectives:
SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms.
Methods:
Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes.
Results:
The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes.
Conclusions
This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.
2.Sex Differences in Procedural Characteristics and Clinical Outcomes Among Patients Undergoing Bifurcation PCI
Hyun Jin AHN ; Francesco BRUNO ; Jeehoon KANG ; Doyeon HWANG ; Han-Mo YANG ; Jung-Kyu HAN ; Leonardo De LUCA ; Ovidio de FILIPPO ; Alessio MATTESINI ; Kyung Woo PARK ; Alessandra TRUFFA ; Wojciech WANHA ; Young Bin SONG ; Sebastiano GILI ; Woo Jung CHUN ; Gerard HELFT ; Seung-Ho HUR ; Bernardo CORTESE ; Seung Hwan HAN ; Javier ESCANED ; Alaide CHIEFFO ; Ki Hong CHOI ; Guglielmo GALLONE ; Joon-Hyung DOH ; Gaetano De FERRARI ; Soon-Jun HONG ; Giorgio QUADRI ; Chang-Wook NAM ; Hyeon-Cheol GWON ; Hyo-Soo KIM ; Fabrizio D’ASCENZO ; Bon-Kwon KOO
Korean Circulation Journal 2025;55(1):5-16
Background and Objectives:
The risk profiles, procedural characteristics, and clinical outcomes for women undergoing bifurcation percutaneous coronary intervention (PCI) are not well defined compared to those in men.
Methods:
COronary BIfurcation Stenting III (COBIS III) is a multicenter, real-world registry of 2,648 patients with bifurcation lesions treated with second-generation drug-eluting stents.We compared the angiographic and procedural characteristics and clinical outcomes based on sex. The primary outcome was 5-year target lesion failure (TLF), a composite of cardiac death, myocardial infarction, and target lesion revascularization.
Results:
Women (n=635, 24%) were older, had hypertension and diabetes more often, and had smaller main vessel and side branch reference diameters than men. The pre- and post-PCI angiographic percentage diameter stenoses of the main vessel and side branch were comparable between women and men. There were no differences in procedural characteristics between the sexes. Women and men had a similar risk of TLF (6.3% vs. 7.1%, p=0.63) as well as its individual components and sex was not an independent predictor of TLF. This finding was consistent in the left main and 2 stenting subgroups.
Conclusions
In patients undergoing bifurcation PCI, sex was not an independent predictor of adverse outcome.
3.The Effects of Nicotine on Re-endothelialization, Inflammation, and Neoatherosclerosis After Drug-Eluting Stent Implantation in a Porcine Model
Seok OH ; Ju Han KIM ; Saleem AHMAD ; Yu Jeong JIN ; Mi Hyang NA ; Munki KIM ; Jeong Ha KIM ; Dae Sung PARK ; Dae Young HYUN ; Kyung Hoon CHO ; Min Chul KIM ; Doo Sun SIM ; Young Joon HONG ; Seung-won LEE ; Youngkeun AHN ; Myung Ho JEONG
Korean Circulation Journal 2025;55(1):50-64
Background and Objectives:
Cigarette smoking is a major risk factor for atherosclerosis.Nicotine, a crucial constituent of tobacco, contributes to atherosclerosis development and progression. However, evidence of the association between nicotine and neointima formation is limited. We aimed to evaluate whether nicotine enhances neointimal hyperplasia in the native epicardial coronary arteries of pigs after percutaneous coronary intervention (PCI) with drug-eluting stents (DES).
Methods:
After coronary angiography (CAG) and quantitative coronary angiography (QCA), we implanted 20 DES into 20 pigs allocated to 2 groups: no-nicotine (n=10) and nicotine (n=10) groups. Post-PCI CAG and QCA were performed immediately. Follow-up CAG, QCA, optical coherence tomography (OCT), and histopathological analyses were performed 2 months post-PCI.
Results:
Despite intergroup similarities in the baseline QCA findings, OCT analysis showed that the nicotine group had a smaller mean stent and lumen areas, a larger mean neointimal area, greater percent area stenosis, and higher peri-strut fibrin and inflammation scores than the no-nicotine group. In immunofluorescence analysis, the nicotine group displayed higher expression of CD68 and α-smooth muscle actin but lower CD31 expression than the no-nicotine group.
Conclusions
Nicotine inhibited re-endothelialization and promoted inflammation and NIH after PCI with DES in a porcine model.
4.Resident shortages and their impact on surgical care, defensive medicine, and patient management: a retrospective study in South Korea
Jeong Hee HAN ; Byoung Chul LEE ; Jung Bum CHOI ; Hong Jae JO ; Jae Kyun PARK ; Hyae Jin KIM ; Eun Ji PARK ; Young Hoon JUNG ; Chang In CHOI
Korean Journal of Clinical Oncology 2025;21(1):32-39
Purpose:
This study aimed to evaluate the impact of declining surgical residency program enrollment on patient care and outcomes in colorectal cancer surgeries.
Methods:
This retrospective observational study included 676 patients (410 males; median age: 69 years) who underwent colorectal cancer surgery at Pusan National University Hospital between January 2018 and June 2024. Patients were divided into Group A (before December 31, 2023; with residents) and Group B (after January 1, 2024; without residents). All surgeries were performed by a single attending surgeon.
Results:
Preoperative variables were comparable between groups. Group A had more emergency and open surgeries, and a higher proportion of advanced-stage cancers. Overall complication rates were similar, but Group B had a longer hospital stay (9.72 days vs. 11.95 days). Specific complications such as anastomotic leakage and surgical site infections differed significantly. The overall number of surgical procedures declined markedly in 2024 compared to 2018 (77.1% vs. 49.9%).
Conclusion
The absence of residents did not increase overall complication rates but was associated with longer hospital stays and shifts in clinical practice. Greater reliance on attending surgeons contributed to more defensive decision-making and conservative patient management. Addressing these issues requires systemic reforms, including multidisciplinary collaboration and legal protections to improve surgical care.
5.Association between Breakfast Consumption Frequency and Chronic Inflammation in Korean Adult Males: Korea National Health and Nutrition Examination Survey 2016–2018
Eun Ji HAN ; Eun Ju PARK ; Sae Rom LEE ; Sang Yeoup LEE ; Young Hye CHO ; Young In LEE ; Jung In CHOI ; Ryuk Jun KWON ; Soo Min SON ; Yun Jin KIM ; Jeong Gyu LEE ; Yu Hyeon YI ; Young Jin TAK ; Seung Hun LEE ; Gyu Lee KIM ; Young Jin RA
Korean Journal of Family Medicine 2025;46(2):92-97
Background:
Skipping breakfast is associated with an increased risk of chronic inflammatory diseases. This study aimed to examine the association between breakfast-eating habits and inflammation, using high-sensitivity C-reactive protein (hs-CRP) as a marker.
Methods:
A total of 4,000 Korean adult males with no history of myocardial infarction, angina, stroke, diabetes, rheumatoid arthritis, cancer, or current smoking were included. Data from the 2016–2018 Korea National Health and Nutrition Examination Survey were used for analysis. The frequency of breakfast consumption was assessed through a questionnaire item in the dietary survey section asking participants about their weekly breakfast consumption routines over the past year. Participants were categorized into two groups, namely “0–2 breakfasts per week” and “3–7 breakfasts per week”; hs-CRP concentrations were measured through blood tests.
Results:
Comparing between the “infrequent breakfast consumption (0–2 breakfasts per week)” and “frequent breakfast consumption (3–7 breakfasts per week)” groups, the mean hs-CRP was found to be significantly higher in the “infrequent breakfast consumption” group, even after adjusting for age, body mass index, physical activity, alcohol consumption, systolic blood pressure, blood pressure medication, fasting blood glucose, and triglycerides (mean hs-CRP: frequent breakfast consumption, 1.36±0.09 mg/L; infrequent breakfast consumption, 1.17±0.05 mg/L; P-value=0.036).
Conclusion
Less frequent breakfast consumption was associated with elevated hs-CRP levels. Further large-scale studies incorporating adjusted measures of daily eating patterns as well as food quality and quantity are required for a deeper understanding of the role of breakfast in the primary prevention of chronic inflammatory diseases.
6.Shank3 Overexpression Leads to Cardiac Dysfunction in Mice by Disrupting Calcium Homeostasis in Cardiomyocytes
Tae Hee KO ; Yoonhee KIM ; Chunmei JIN ; Byeongil YU ; Minju LEE ; Phuong Kim LUONG ; Tran Nguyet TRINH ; Yeji YANG ; Hyojin KANG ; Yinhua ZHANG ; Ruiying MA ; Kwangmin YOO ; Jungmin CHOI ; Jin Young KIM ; Sun-Hee WOO ; Kihoon HAN ; Jong-Il CHOI
Korean Circulation Journal 2025;55(2):100-117
Background and Objectives:
SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms.
Methods:
Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes.
Results:
The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes.
Conclusions
This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.
7.Sex Differences in Procedural Characteristics and Clinical Outcomes Among Patients Undergoing Bifurcation PCI
Hyun Jin AHN ; Francesco BRUNO ; Jeehoon KANG ; Doyeon HWANG ; Han-Mo YANG ; Jung-Kyu HAN ; Leonardo De LUCA ; Ovidio de FILIPPO ; Alessio MATTESINI ; Kyung Woo PARK ; Alessandra TRUFFA ; Wojciech WANHA ; Young Bin SONG ; Sebastiano GILI ; Woo Jung CHUN ; Gerard HELFT ; Seung-Ho HUR ; Bernardo CORTESE ; Seung Hwan HAN ; Javier ESCANED ; Alaide CHIEFFO ; Ki Hong CHOI ; Guglielmo GALLONE ; Joon-Hyung DOH ; Gaetano De FERRARI ; Soon-Jun HONG ; Giorgio QUADRI ; Chang-Wook NAM ; Hyeon-Cheol GWON ; Hyo-Soo KIM ; Fabrizio D’ASCENZO ; Bon-Kwon KOO
Korean Circulation Journal 2025;55(1):5-16
Background and Objectives:
The risk profiles, procedural characteristics, and clinical outcomes for women undergoing bifurcation percutaneous coronary intervention (PCI) are not well defined compared to those in men.
Methods:
COronary BIfurcation Stenting III (COBIS III) is a multicenter, real-world registry of 2,648 patients with bifurcation lesions treated with second-generation drug-eluting stents.We compared the angiographic and procedural characteristics and clinical outcomes based on sex. The primary outcome was 5-year target lesion failure (TLF), a composite of cardiac death, myocardial infarction, and target lesion revascularization.
Results:
Women (n=635, 24%) were older, had hypertension and diabetes more often, and had smaller main vessel and side branch reference diameters than men. The pre- and post-PCI angiographic percentage diameter stenoses of the main vessel and side branch were comparable between women and men. There were no differences in procedural characteristics between the sexes. Women and men had a similar risk of TLF (6.3% vs. 7.1%, p=0.63) as well as its individual components and sex was not an independent predictor of TLF. This finding was consistent in the left main and 2 stenting subgroups.
Conclusions
In patients undergoing bifurcation PCI, sex was not an independent predictor of adverse outcome.
8.The Effects of Nicotine on Re-endothelialization, Inflammation, and Neoatherosclerosis After Drug-Eluting Stent Implantation in a Porcine Model
Seok OH ; Ju Han KIM ; Saleem AHMAD ; Yu Jeong JIN ; Mi Hyang NA ; Munki KIM ; Jeong Ha KIM ; Dae Sung PARK ; Dae Young HYUN ; Kyung Hoon CHO ; Min Chul KIM ; Doo Sun SIM ; Young Joon HONG ; Seung-won LEE ; Youngkeun AHN ; Myung Ho JEONG
Korean Circulation Journal 2025;55(1):50-64
Background and Objectives:
Cigarette smoking is a major risk factor for atherosclerosis.Nicotine, a crucial constituent of tobacco, contributes to atherosclerosis development and progression. However, evidence of the association between nicotine and neointima formation is limited. We aimed to evaluate whether nicotine enhances neointimal hyperplasia in the native epicardial coronary arteries of pigs after percutaneous coronary intervention (PCI) with drug-eluting stents (DES).
Methods:
After coronary angiography (CAG) and quantitative coronary angiography (QCA), we implanted 20 DES into 20 pigs allocated to 2 groups: no-nicotine (n=10) and nicotine (n=10) groups. Post-PCI CAG and QCA were performed immediately. Follow-up CAG, QCA, optical coherence tomography (OCT), and histopathological analyses were performed 2 months post-PCI.
Results:
Despite intergroup similarities in the baseline QCA findings, OCT analysis showed that the nicotine group had a smaller mean stent and lumen areas, a larger mean neointimal area, greater percent area stenosis, and higher peri-strut fibrin and inflammation scores than the no-nicotine group. In immunofluorescence analysis, the nicotine group displayed higher expression of CD68 and α-smooth muscle actin but lower CD31 expression than the no-nicotine group.
Conclusions
Nicotine inhibited re-endothelialization and promoted inflammation and NIH after PCI with DES in a porcine model.
9.Resident shortages and their impact on surgical care, defensive medicine, and patient management: a retrospective study in South Korea
Jeong Hee HAN ; Byoung Chul LEE ; Jung Bum CHOI ; Hong Jae JO ; Jae Kyun PARK ; Hyae Jin KIM ; Eun Ji PARK ; Young Hoon JUNG ; Chang In CHOI
Korean Journal of Clinical Oncology 2025;21(1):32-39
Purpose:
This study aimed to evaluate the impact of declining surgical residency program enrollment on patient care and outcomes in colorectal cancer surgeries.
Methods:
This retrospective observational study included 676 patients (410 males; median age: 69 years) who underwent colorectal cancer surgery at Pusan National University Hospital between January 2018 and June 2024. Patients were divided into Group A (before December 31, 2023; with residents) and Group B (after January 1, 2024; without residents). All surgeries were performed by a single attending surgeon.
Results:
Preoperative variables were comparable between groups. Group A had more emergency and open surgeries, and a higher proportion of advanced-stage cancers. Overall complication rates were similar, but Group B had a longer hospital stay (9.72 days vs. 11.95 days). Specific complications such as anastomotic leakage and surgical site infections differed significantly. The overall number of surgical procedures declined markedly in 2024 compared to 2018 (77.1% vs. 49.9%).
Conclusion
The absence of residents did not increase overall complication rates but was associated with longer hospital stays and shifts in clinical practice. Greater reliance on attending surgeons contributed to more defensive decision-making and conservative patient management. Addressing these issues requires systemic reforms, including multidisciplinary collaboration and legal protections to improve surgical care.
10.Association between Breakfast Consumption Frequency and Chronic Inflammation in Korean Adult Males: Korea National Health and Nutrition Examination Survey 2016–2018
Eun Ji HAN ; Eun Ju PARK ; Sae Rom LEE ; Sang Yeoup LEE ; Young Hye CHO ; Young In LEE ; Jung In CHOI ; Ryuk Jun KWON ; Soo Min SON ; Yun Jin KIM ; Jeong Gyu LEE ; Yu Hyeon YI ; Young Jin TAK ; Seung Hun LEE ; Gyu Lee KIM ; Young Jin RA
Korean Journal of Family Medicine 2025;46(2):92-97
Background:
Skipping breakfast is associated with an increased risk of chronic inflammatory diseases. This study aimed to examine the association between breakfast-eating habits and inflammation, using high-sensitivity C-reactive protein (hs-CRP) as a marker.
Methods:
A total of 4,000 Korean adult males with no history of myocardial infarction, angina, stroke, diabetes, rheumatoid arthritis, cancer, or current smoking were included. Data from the 2016–2018 Korea National Health and Nutrition Examination Survey were used for analysis. The frequency of breakfast consumption was assessed through a questionnaire item in the dietary survey section asking participants about their weekly breakfast consumption routines over the past year. Participants were categorized into two groups, namely “0–2 breakfasts per week” and “3–7 breakfasts per week”; hs-CRP concentrations were measured through blood tests.
Results:
Comparing between the “infrequent breakfast consumption (0–2 breakfasts per week)” and “frequent breakfast consumption (3–7 breakfasts per week)” groups, the mean hs-CRP was found to be significantly higher in the “infrequent breakfast consumption” group, even after adjusting for age, body mass index, physical activity, alcohol consumption, systolic blood pressure, blood pressure medication, fasting blood glucose, and triglycerides (mean hs-CRP: frequent breakfast consumption, 1.36±0.09 mg/L; infrequent breakfast consumption, 1.17±0.05 mg/L; P-value=0.036).
Conclusion
Less frequent breakfast consumption was associated with elevated hs-CRP levels. Further large-scale studies incorporating adjusted measures of daily eating patterns as well as food quality and quantity are required for a deeper understanding of the role of breakfast in the primary prevention of chronic inflammatory diseases.

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