1.Association of Obesity Status Trajectories with Changes in Prediabetes Glycemic Status
Salma NABILA ; Ji-Eun KIM ; JooYong PARK ; Hyojin KIM ; Seokyung HAHN ; Aesun SHIN ; Daehee KANG ; Ji-Yeob CHOI
Journal of Cancer Prevention 2026;31(1):28-37
This study aimed to determine the association between trajectories of obesity status and prediabetes reversion to normoglycemia or progression to diabetes. The study included 14,452 participants from the National Health Insurance Service-National Health Screening (NHIS-HEALS) cohort who continuously had prediabetes glycemic status during the index period (2002-2008), definedby their fasting plasma glucose. The exposure of the study was the trajectories of obesity (defined by body mass index ≥ 25 kg/m 2 ) generated using latent class growth analysis. The outcomes were reversion to normoglycemia or progression to diabetes, whichever occurred first during the follow-up period (2009-2016). The association between trajectories and changes in prediabetes status were examined using cause-specific hazard regression by obtaining the hazard ratio (HR) with a 95% CI. We identified three distinct trajectories which were “Stable obese”, “Stable non-obese” and “Obese to non-obese”. After a median follow-up of 2years, 51.99% of participants had their glycemic status back to normoglycemia and 32.17% developed diabetes. Compared with participants in the “Stable obese” group, those in “Stable non-obese” and “Obese to non-obese” groups were more likely to have reversion to normoglycemia (HR with a 95% CI = 1.30 [1.23-1.37] and 1.15 [1.07-1.24], respectively) and lower risk of developingdiabetes (0.78 [0.73-0.84] and 0.90 [0.82-0.98], respectively). The findings suggest that maintaining or achieving a non-obese sta-tus is linked to higher reversion to normoglycemia as well as lower risks of developing diabetes.
2.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.
3.Association between preoperative oxygen reserve index and postoperative pulmonary complications: a prospective observational study
Sangho LEE ; Halin HONG ; Hyojin CHO ; Sang-Wook LEE ; Ann Hee YOU ; Hee Yong KANG ; Sung Wook PARK ; Mi Kyeong KIM ; Jeong-Hyun CHOI
Korean Journal of Anesthesiology 2025;78(3):224-235
Background:
The oxygen reserve index (ORi) noninvasively measures oxygen levels within the mild hyperoxia range. To evaluate whether a degree of increase in the ORi during preoxygenation for general anesthesia is associated with the occurrence of postoperative pulmonary complications (PPCs).
Methods:
We enrolled 154 patients who underwent preoperative pulmonary function tests and were scheduled for elective surgery under general anesthesia. We aimed to measure the increase in ORi during preoxygenation before general anesthesia and analyze its association with PPCs.
Results:
PPCs occurred in 76 (49%) participants. Multivariate logistic regression analysis revealed that the three-minute preoxygenation ORi was significantly associated with PPCs (Odds ratio [OR]: 0.02, 95% CI [0.00–0.16], P < 0.001). The areas under the curve (AUC [95% CI]) in the receiver operating characteristic curve analysis for the three-minute preoxygenation ORi for PPCs were 0.64 (0.55–0.73). After a subgroup analysis, multivariate logistic regression showed that the three-minute preoxygenation ORi was significantly associated with PPCs among patients who underwent thoracic surgery (OR: 0.01, 95% CI [0.00–0.19], P = 0.006). The AUC of the three-minute preoxygenation ORi for PPCs was 0.72 (0.57–0.86) in patients who underwent thoracic surgery.
Conclusions
A low ORi measured after 3 min of preoxygenation for general anesthesia was associated with an increased risk of PPCs, including those undergoing thoracic surgery. This study demonstrated the potential of ORi, measured after oxygen administration, as a tool for evaluating lung function that complements traditional lung function tests and scoring systems.
4.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.
5.Association between preoperative oxygen reserve index and postoperative pulmonary complications: a prospective observational study
Sangho LEE ; Halin HONG ; Hyojin CHO ; Sang-Wook LEE ; Ann Hee YOU ; Hee Yong KANG ; Sung Wook PARK ; Mi Kyeong KIM ; Jeong-Hyun CHOI
Korean Journal of Anesthesiology 2025;78(3):224-235
Background:
The oxygen reserve index (ORi) noninvasively measures oxygen levels within the mild hyperoxia range. To evaluate whether a degree of increase in the ORi during preoxygenation for general anesthesia is associated with the occurrence of postoperative pulmonary complications (PPCs).
Methods:
We enrolled 154 patients who underwent preoperative pulmonary function tests and were scheduled for elective surgery under general anesthesia. We aimed to measure the increase in ORi during preoxygenation before general anesthesia and analyze its association with PPCs.
Results:
PPCs occurred in 76 (49%) participants. Multivariate logistic regression analysis revealed that the three-minute preoxygenation ORi was significantly associated with PPCs (Odds ratio [OR]: 0.02, 95% CI [0.00–0.16], P < 0.001). The areas under the curve (AUC [95% CI]) in the receiver operating characteristic curve analysis for the three-minute preoxygenation ORi for PPCs were 0.64 (0.55–0.73). After a subgroup analysis, multivariate logistic regression showed that the three-minute preoxygenation ORi was significantly associated with PPCs among patients who underwent thoracic surgery (OR: 0.01, 95% CI [0.00–0.19], P = 0.006). The AUC of the three-minute preoxygenation ORi for PPCs was 0.72 (0.57–0.86) in patients who underwent thoracic surgery.
Conclusions
A low ORi measured after 3 min of preoxygenation for general anesthesia was associated with an increased risk of PPCs, including those undergoing thoracic surgery. This study demonstrated the potential of ORi, measured after oxygen administration, as a tool for evaluating lung function that complements traditional lung function tests and scoring systems.
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.Association between preoperative oxygen reserve index and postoperative pulmonary complications: a prospective observational study
Sangho LEE ; Halin HONG ; Hyojin CHO ; Sang-Wook LEE ; Ann Hee YOU ; Hee Yong KANG ; Sung Wook PARK ; Mi Kyeong KIM ; Jeong-Hyun CHOI
Korean Journal of Anesthesiology 2025;78(3):224-235
Background:
The oxygen reserve index (ORi) noninvasively measures oxygen levels within the mild hyperoxia range. To evaluate whether a degree of increase in the ORi during preoxygenation for general anesthesia is associated with the occurrence of postoperative pulmonary complications (PPCs).
Methods:
We enrolled 154 patients who underwent preoperative pulmonary function tests and were scheduled for elective surgery under general anesthesia. We aimed to measure the increase in ORi during preoxygenation before general anesthesia and analyze its association with PPCs.
Results:
PPCs occurred in 76 (49%) participants. Multivariate logistic regression analysis revealed that the three-minute preoxygenation ORi was significantly associated with PPCs (Odds ratio [OR]: 0.02, 95% CI [0.00–0.16], P < 0.001). The areas under the curve (AUC [95% CI]) in the receiver operating characteristic curve analysis for the three-minute preoxygenation ORi for PPCs were 0.64 (0.55–0.73). After a subgroup analysis, multivariate logistic regression showed that the three-minute preoxygenation ORi was significantly associated with PPCs among patients who underwent thoracic surgery (OR: 0.01, 95% CI [0.00–0.19], P = 0.006). The AUC of the three-minute preoxygenation ORi for PPCs was 0.72 (0.57–0.86) in patients who underwent thoracic surgery.
Conclusions
A low ORi measured after 3 min of preoxygenation for general anesthesia was associated with an increased risk of PPCs, including those undergoing thoracic surgery. This study demonstrated the potential of ORi, measured after oxygen administration, as a tool for evaluating lung function that complements traditional lung function tests and scoring systems.
8.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.
9.Association between preoperative oxygen reserve index and postoperative pulmonary complications: a prospective observational study
Sangho LEE ; Halin HONG ; Hyojin CHO ; Sang-Wook LEE ; Ann Hee YOU ; Hee Yong KANG ; Sung Wook PARK ; Mi Kyeong KIM ; Jeong-Hyun CHOI
Korean Journal of Anesthesiology 2025;78(3):224-235
Background:
The oxygen reserve index (ORi) noninvasively measures oxygen levels within the mild hyperoxia range. To evaluate whether a degree of increase in the ORi during preoxygenation for general anesthesia is associated with the occurrence of postoperative pulmonary complications (PPCs).
Methods:
We enrolled 154 patients who underwent preoperative pulmonary function tests and were scheduled for elective surgery under general anesthesia. We aimed to measure the increase in ORi during preoxygenation before general anesthesia and analyze its association with PPCs.
Results:
PPCs occurred in 76 (49%) participants. Multivariate logistic regression analysis revealed that the three-minute preoxygenation ORi was significantly associated with PPCs (Odds ratio [OR]: 0.02, 95% CI [0.00–0.16], P < 0.001). The areas under the curve (AUC [95% CI]) in the receiver operating characteristic curve analysis for the three-minute preoxygenation ORi for PPCs were 0.64 (0.55–0.73). After a subgroup analysis, multivariate logistic regression showed that the three-minute preoxygenation ORi was significantly associated with PPCs among patients who underwent thoracic surgery (OR: 0.01, 95% CI [0.00–0.19], P = 0.006). The AUC of the three-minute preoxygenation ORi for PPCs was 0.72 (0.57–0.86) in patients who underwent thoracic surgery.
Conclusions
A low ORi measured after 3 min of preoxygenation for general anesthesia was associated with an increased risk of PPCs, including those undergoing thoracic surgery. This study demonstrated the potential of ORi, measured after oxygen administration, as a tool for evaluating lung function that complements traditional lung function tests and scoring systems.
10.Functional Annotation and Gene Set Analysis of Gastric Cancer Risk Loci in a Korean Population
Hyojin PYUN ; Madhawa GUNATHILAKE ; Jeonghee LEE ; Il Ju CHOI ; Young-Il KIM ; Joohon SUNG ; Jeongseon KIM
Cancer Research and Treatment 2024;56(1):191-198
Purpose:
We aimed to identify the associated single nucleotide polymorphisms (SNPs) with gastric cancer (GC) risk by genome-wide association study (GWAS) and to explore the pathway enrichment of implicated genes and gene-sets with expression patterns.
Materials and Methods:
The study population was comprised of 1,253 GC cases and 4,827 controls from National Cancer Center and an urban community of the Korean Genome Epidemiology Study and their genotyping was performed. SNPs were annotated, and mapped to genes to prioritize by three mapping approaches by functional mapping and annotation (FUMA). The gene-based analysis and gene-set analysis were conducted with full GWAS summary data using MAGMA. Gene-set pathway enrichment test with those prioritized genes were performed.
Results:
In GWAS, rs2303771, a nonsynonymous variant of KLHDC4 gene was top SNP associated significantly with GC (odds ratio, 2.59; p=1.32×10–83). In post-GWAS, 71 genes were prioritized. In gene-based GWAS, seven genes were under significant p < 3.80×10–6 (0.05/13,114); DEFB108B had the lowest p=5.94×10–15, followed by FAM86C1 (p=1.74×10–14), PSCA (p=1.81×10–14), and KLHDC4 (p=5.00×10–10). In gene prioritizing, KLDHC4 was the only gene mapped with all three gene-mapping approaches. In pathway enrichment test with prioritized genes, FOLR2, PSCA, LY6K, LYPD2, and LY6E showed strong enrichment related to cellular component of membrane; a post-translation modification by synthesis of glycosylphosphatidylinositol (GPI)-anchored proteins pathway.
Conclusion
While 37 SNPs were significantly associated with the risk of GC, genes involved in signaling pathways related to purine metabolism and GPI-anchored protein in cell membrane are pinpointed to be playing important role in GC.

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