1.Rosuvastatin activates autophagy via inhibition of the Akt/mTOR axis in vascular smooth muscle cells
Seongpyo LEE ; Do-Hyung LEE ; Jin-Pyo LEE ; Joo-Hui HAN
The Korean Journal of Physiology and Pharmacology 2025;29(1):117-126
The proliferation and migration of vascular smooth muscle cells (VSMCs) are key contributors to the development of atherosclerosis and restenosis. We investigated the impact of rosuvastatin (RSV) on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of VSMCs, with a focus on the Akt/mTORautophagy signaling pathways. The cytotoxicity of RSV was assessed using MTT and annexin V staining, while the proliferation and migration capabilities of PDGF-BBinduced VSMCs were evaluated using MTT and cell migration assays. Confocal microscopy was employed to examine autophagic cell images, and protein expressions were analyzed via Western blotting. Our key findings revealed that RSV inhibited PDGF-BB-induced proliferation and migration of VSMCs, significantly reducing the expression of proliferating cell nuclear antigen and matrix metalloproteinase-2, which are crucial for these processes. RSV also enhanced autophagy in PDGF-BBstimulated cells by inducing the maturation of microtubule-associated protein light chain 3 and increasing the expression of Beclin-1, autophagy related (Atg)3, Atg5, and Atg7. The regulatory effects of RSV on PDGF-BB-induced autophagy, proliferation, and migration were associated with the suppression of the Akt/mTOR signaling pathway. These findings suggest that RSV may have potential therapeutic benefits in preventing and treating vascular diseases by targeting the Akt/mTOR pathway and inducing autophagy.
2.Glutathione’s Role in Liver Metabolism and Hangover Symptom Relief: Dysregulation of Protein S-Glutathionylation and Antioxidant Enzymes
Hwa-Young LEE ; Geum-Hwa LEE ; Do-Sung KIM ; Young Jae LIM ; Boram CHO ; Hojung JUNG ; Hyun-shik CHOI ; Soonok SA ; Wookyung CHUNG ; Hyewon LEE ; Myoung Ja CHUNG ; Junghyun KIM ; Han-Jung CHAE
Biomolecules & Therapeutics 2025;33(1):117-128
Hangovers from alcohol consumption cause symptoms like headaches, nausea, and fatigue, disrupting daily activities and overall well-being. Over time, they can also lead to inflammation and oxidative stress. Effective hangover relief alleviates symptoms, prevents dehydration, and replenishes energy needed for daily tasks. Natural foods considered high in antioxidants and antiinflammatory properties may aid in the hepatic breakdown of alcohol. The study aims to investigate the impact of glutathione or its enriched yeast extract, which is recognized for its antioxidant characteristics, on alcohol metabolism and alleviating hangovers in a rat model exposed to binge drinking. In this study, glutathione and its enriched yeast extract controlled hangover behaviour patterns, including locomotor activity. Additionally, it enhanced the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) following ethanol ingestion (3 g/kg). Further, the incorporation of glutathione led to an increase in the expression of antioxidant enzymes, such as SOD and catalase, by activating the nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway.This activation reduced the excessive production of reactive oxygen species (ROS) and malondialdehyde. Next, glutathione modulated the activity of cytochrome P450 2E1 (CYP2E1) and the protein expressions of Bax and Bcl2. Besides, in vitro and in vivo investigations with glutathione demonstrated a regulating effect on the pan-s-glutathionylation and its associated protein expression, glutaredoxin 1 (Grx1), glutathione-S-transferase Pi (GST-π), and glutathione reductase (GR). Together, these findings suggest that glutathione or its enriched yeast extract as a beneficial dietary supplement for alleviating hangover symptoms by enhancing alcohol metabolism and its associated Nrf2/Keap1 signalings.
3.Satisfactory Clinical Outcomes of Revision Anterior Cruciate Ligament Reconstruction Using Quadriceps Tendon-Patellar Bone Allograft
Do Weon LEE ; Sanguk LEE ; Du Hyun RO ; Hyuk-Soo HAN
Clinics in Orthopedic Surgery 2025;17(1):91-99
Background:
Allografts are preferred in certain cases of revision anterior cruciate ligament reconstructions to avoid additional graft harvesting and to fill in enlarged tunnels. The clinical outcomes of quadriceps tendon-patellar bone allograft in revision anterior cruciate ligament reconstruction are not well-known. This study was performed to evaluate the clinical outcomes of revision anterior cruciate ligament reconstructions using quadriceps tendon-patellar bone allografts.
Methods:
Patients who underwent revision anterior cruciate ligament reconstructions with quadriceps tendon-patellar bone allografts with a minimum follow-up of 2 years were retrospectively reviewed. Their mean follow-up length was 33.5 ± 19.5 months.Outcomes including clinical scores (Lysholm, International Knee Documentation Committee [IKDC], Tegner scale, and Knee injury and Osteoarthritis Outcome Score [KOOS]), knee stability (physical examinations and knee arthrometer), return to sports, and any associated complications were assessed. Degrees of graft synovialization were also evaluated using arthroscopy.
Results:
A total of 38 patients were reviewed and their age at the time of surgery and follow-up length were 37.2 ± 12.5 years (range, 17–66 years) and 2.8 ± 1.6 years, respectively. All clinical scores including KOOS, IKDC, Lysholm, and Tegner scale significantly improved at 2 years after surgery and 92.1% of the patients returned to sports. The mean preoperative side-to-side difference in knee arthrometer decreased from 4.5 ± 2.3 mm before surgery to 2.6 ± 1.5 mm after surgery (p < 0.001). Graft synovialization was observed in 13 of 16 patients (81.3%) who underwent second-look arthroscopy. Complication rate was 10.5% (n = 4). All complications were graft re-rupture and occurred at an average of 18 months after revision surgery.
Conclusions
Quadriceps tendon-patellar bone allograft showed satisfactory clinical outcomes in revision anterior cruciate ligament reconstruction and thus could be a good alternative when autograft harvesting is not optimal.
4.Connection between Impaired Fasting Glucose or Type 2 Diabetes Mellitus and Sepsis: A 10-Year Observational Data from the National Health Screening Cohort
Eun Hwa LEE ; Kyoung Hwa LEE ; Kyu-na LEE ; Yebin PARK ; Kyung Do HAN ; Sang Hoon HAN
Diabetes & Metabolism Journal 2025;49(3):485-497
Background:
The mortality of sepsis without direct drugs is high. The association between prediabetes, based on a single fasting glucose (FG), or long-term type 2 diabetes mellitus (T2DM) and sepsis remains unclear.
Methods:
Of the adults aged ≥20 years who were included in the National Health Screening Program (NHSP) in 2009, 40% were randomly sampled. After excluding patients with type 1 diabetes mellitus, with missing information, and who were diagnosed with sepsis during the wash-out (between 2001 and the NHSP) or 1-year lag period, a cohort comprised of 3,863,323 examinees. Body mass index (BMI) measurements, FG tests, and self-reported questionnaires on health-related behaviors were conducted. Individual information was followed up until 2020 and censored upon the first occurrence of sepsis or death. The incidence of sepsis was compared using a multivariable regression adjusted for age, sex, income, BMI, smoking, drinking, physical activity levels, and chronic diseases.
Results:
The cohort was divided into those with normal FG (n=2,675,476), impaired fasting glucose (IFG) (n=890,402, 23.0%), T2DM <5 years (n=212,391, 5.5%), or T2DM for ≥5 years (n=85,054, 2.2%). The groups with IFG (adjusted hazard ratio [aHR], 1.03; 95% confidence interval [CI], 1.01 to 1.05), T2DM <5 years (aHR, 1.43; 95% CI, 1.40 to 1.47), and T2DM for ≥5 years (aHR, 1.82; 95% CI, 1.77 to 1.87) exhibited significantly higher incidence of sepsis (P<0.001), with the greatest risk in patients with T2DM aged <40 years (aHR, 1.96; 95% CI, 1.71 to 2.25).
Conclusion
Patients with long-standing and young-onset T2DM show a substantially high risk of sepsis, emphasizing the need for infection prevention and vaccination.
5.Predicting Mortality and Cirrhosis-Related Complications with MELD3.0: A Multicenter Cohort Analysis
Jihye LIM ; Ji Hoon KIM ; Ahlim LEE ; Ji Won HAN ; Soon Kyu LEE ; Hyun YANG ; Heechul NAM ; Hae Lim LEE ; Do Seon SONG ; Sung Won LEE ; Hee Yeon KIM ; Jung Hyun KWON ; Chang Wook KIM ; U Im CHANG ; Soon Woo NAM ; Seok-Hwan KIM ; Pil Soo SUNG ; Jeong Won JANG ; Si Hyun BAE ; Jong Young CHOI ; Seung Kew YOON ; Myeong Jun SONG
Gut and Liver 2025;19(3):427-437
Background/Aims:
This study aimed to evaluate the performance of the Model for End-Stage Liver Disease (MELD) 3.0 for predicting mortality and liver-related complications compared with the Child-Pugh classification, albumin-bilirubin (ALBI) grade, the MELD, and the MELD sodium (MELDNa) score.
Methods:
We evaluated a multicenter retrospective cohort of incorporated patients with cirrhosis between 2013 and 2019. We conducted comparisons of the area under the receiver operating characteristic curve (AUROC) of the MELD3.0 and other models for predicting 3-month mortality. Additionally, we assessed the risk of cirrhosis-related complications according to the MELD3.0 score.
Results:
A total of 3,314 patients were included. The mean age was 55.9±11.3 years, and 70.2% of the patients were male. Within the initial 3 months, 220 patients (6.6%) died, and the MELD3.0had the best predictive performance among the tested models, with an AUROC of 0.851, outperforming the Child-Pugh classification, ALBI grade, MELD, and MELDNa. A high MELD3.0score was associated with an increased risk of mortality. Compared with that of the group with a MELD3.0 score <10 points, the adjusted hazard ratio of the group with a score of 10–20 pointswas 2.176, and that for the group with a score of ≥20 points was 4.892. Each 1-point increase inthe MELD3.0 score increased the risk of cirrhosis-related complications by 1.033-fold. The risk of hepatorenal syndrome showed the highest increase, with an adjusted hazard ratio of 1.149, followed by hepatic encephalopathy and ascites.
Conclusions
The MELD3.0 demonstrated robust prognostic performance in predicting mortality in patients with cirrhosis. Moreover, the MELD3.0 score was linked to cirrhosis-related complications, particularly those involving kidney function, such as hepatorenal syndrome and ascites.
6.A nationwide survey on the curriculum and educational resources related to the Clinical Skills Test of the Korean Medical Licensing Examination: a cross-sectional descriptive study
Eun-Kyung CHUNG ; Seok Hoon KANG ; Do-Hoon KIM ; MinJeong KIM ; Ji-Hyun SEO ; Keunmi LEE ; Eui-Ryoung HAN
Journal of Educational Evaluation for Health Professions 2025;22(1):11-
Purpose:
The revised Clinical Skills Test (CST) of the Korean Medical Licensing Exam aims to provide a better assessment of physicians’ clinical competence and ability to interact with patients. This study examined the impact of the revised CST on medical education curricula and resources nationwide, while also identifying areas for improvement within the revised CST.
Methods:
This study surveyed faculty responsible for clinical clerkships at 40 medical schools throughout Korea to evaluate the status and changes in clinical skills education, assessment, and resources related to the CST. The researchers distributed the survey via email through regional consortia between December 7, 2023 and January 19, 2024.
Results:
Nearly all schools implemented preliminary student–patient encounters during core clinical rotations. Schools primarily conducted clinical skills assessments in the third and fourth years, with a simplified form introduced in the first and second years. Remedial education was conducted through various methods, including one-on-one feedback from faculty after the assessment. All schools established clinical skills centers and made ongoing improvements. Faculty members did not perceive the CST revisions as significantly altering clinical clerkship or skills assessments. They suggested several improvements, including assessing patient records to improve accuracy and increasing the objectivity of standardized patient assessments to ensure fairness.
Conclusion
During the CST, students’ involvement in patient encounters and clinical skills education increased, improving the assessment and feedback processes for clinical skills within the curriculum. To enhance students’ clinical competencies and readiness, strengthening the validity and reliability of the CST is essential.
7.Prospective Multicenter Observational Study on Postoperative Quality of Life According to Type of Gastrectomy for Gastric Cancer
Sung Eun OH ; Yun-Suhk SUH ; Ji Yeong AN ; Keun Won RYU ; In CHO ; Sung Geun KIM ; Ji-Ho PARK ; Hoon HUR ; Hyung-Ho KIM ; Sang-Hoon AHN ; Sun-Hwi HWANG ; Hong Man YOON ; Ki Bum PARK ; Hyoung-Il KIM ; In Gyu KWON ; Han-Kwang YANG ; Byoung-Jo SUH ; Sang-Ho JEONG ; Tae-Han KIM ; Oh Kyoung KWON ; Hye Seong AHN ; Ji Yeon PARK ; Ki Young YOON ; Myoung Won SON ; Seong-Ho KONG ; Young-Gil SON ; Geum Jong SONG ; Jong Hyuk YUN ; Jung-Min BAE ; Do Joong PARK ; Sol LEE ; Jun-Young YANG ; Kyung Won SEO ; You-Jin JANG ; So Hyun KANG ; Bang Wool EOM ; Joongyub LEE ; Hyuk-Joon LEE ;
Journal of Gastric Cancer 2025;25(2):382-399
Purpose:
This study evaluated the postoperative quality of life (QoL) after various types of gastrectomy for gastric cancer.
Materials and Methods:
A multicenter prospective observational study was conducted in Korea using the Korean Quality of Life in Stomach Cancer Patients Study (KOQUSS)-40, a new QoL assessment tool focusing on postgastrectomy syndrome. Overall, 496 patients with gastric cancer were enrolled, and QoL was assessed at 5 time points: preoperatively and at 1, 3, 6, and 12 months after surgery.
Results:
Distal gastrectomy (DG) and pylorus-preserving gastrectomy (PPG) showed significantly better outcomes than total gastrectomy (TG) and proximal gastrectomy (PG) with regard to total score, indigestion, and dysphagia. DG, PPG, and TG also showed significantly better outcomes than PG in terms of dumping syndrome and worry about cancer. Postoperative QoL did not differ significantly according to anastomosis type in DG, except for Billroth I anastomosis, which achieved better bowel habit change scores than the others. No domains differed significantly when comparing double tract reconstruction and esophagogastrostomy after PG. The total QoL score correlated significantly with postoperative body weight loss (more than 10%) and extent of resection (P<0.05 for both).Reflux as assessed by KOQUSS-40 did not correlate significantly with reflux observed on gastroscopy 1 year postoperatively (P=0.064).
Conclusions
Our prospective observation using KOQUSS-40 revealed that DG and PPG lead to better QoL than TG and PG. Further study is needed to compare postoperative QoL according to anastomosis type in DG and PG.
8.Is Braun Jejunojejunostomy Necessary? Comparison Between Billroth-II Alone and Billroth-II With Braun Anastomosis After Distal Gastrectomy
Jane Chungyoon KIM ; Min Jung LEE ; Hyuk-Joon LEE ; Kyoyoung PARK ; Min Kyu KANG ; Sa-Hong KIM ; Chun ZHUANG ; Abdullah ALMAYOUF ; Ma. Jeanesse C. BERNARDO ; Jeesun KIM ; Yo-Seok CHO ; Seong-Ho KONG ; Soo-Jeong CHO ; Do Joong PARK ; Han-Kwang YANG
Journal of Gastric Cancer 2025;25(2):318-329
Purpose:
The optimal reconstruction method following distal gastrectomy has not been elucidated. Since Billroth-II (B-II) reconstruction is commonly associated with increased bile reflux, Braun jejunojejunostomy has been proposed to reduce this complication.
Materials and Methods:
We retrospectively analyzed 325 patients with gastric cancer who underwent distal gastrectomy with B-II reconstruction between January 2015 and December 2017, comprising 159 patients without Braun anastomosis and 166 with Braun anastomosis.Outcomes were assessed over three years using annual gastroscopy based on the residual food, gastritis, and bile reflux criteria and the Los Angeles classification for reflux esophagitis.
Results:
In the first postoperative year, the group with Braun anastomosis showed a significant reduction in bile reflux compared to the group without Braun anastomosis (75.9% vs. 86.2%; P=0.019). Moreover, multivariate analysis identified Braun anastomosis as the sole factor associated with this outcome. Additionally, the group with Braun anastomosis had a lower incidence of heartburn (12.0% vs. 20.1%; P=0.047) and reduced use of prokinetics (P<0.001) and acid reducers (P=0.002) compared to the group without Braun anastomosis.However, these benefits diminished in subsequent years, with no significant differences in residual food, gastritis, or reflux esophagitis between the groups. Both groups showed similar body mass index scores and nutritional outcomes over the 3-year follow-up period.
Conclusions
Although Braun anastomosis offers short-term benefits in reducing bile reflux after B-II reconstruction, these effects are not sustainable. The routine use of Braun anastomosis should be reconsidered, though either approach remains a viable option depending on the patient’s circumstances.
9.Long-Term Incidence of Gastrointestinal Bleeding Following Ischemic Stroke
Jun Yup KIM ; Beom Joon KIM ; Jihoon KANG ; Do Yeon KIM ; Moon-Ku HAN ; Seong-Eun KIM ; Heeyoung LEE ; Jong-Moo PARK ; Kyusik KANG ; Soo Joo LEE ; Jae Guk KIM ; Jae-Kwan CHA ; Dae-Hyun KIM ; Tai Hwan PARK ; Kyungbok LEE ; Hong-Kyun PARK ; Yong-Jin CHO ; Keun-Sik HONG ; Kang-Ho CHOI ; Joon-Tae KIM ; Dong-Eog KIM ; Jay Chol CHOI ; Mi-Sun OH ; Kyung-Ho YU ; Byung-Chul LEE ; Kwang-Yeol PARK ; Ji Sung LEE ; Sujung JANG ; Jae Eun CHAE ; Juneyoung LEE ; Min-Surk KYE ; Philip B. GORELICK ; Hee-Joon BAE ;
Journal of Stroke 2025;27(1):102-112
Background:
and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes.
Methods:
We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data.
Results:
Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4.
Conclusion
Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.
10.Comparison of Higher-order Aberrations Outcomes between Sutured Scleral Fixation and Modified Yamane Sutureless Scleral Fixation
Dong Jin HAN ; Myung Jun SEONG ; Jong Min LEE ; Jong Hyun LEE ; Do Hyung LEE ; Min Kyung SONG ; Hun JIn CHOI
Journal of the Korean Ophthalmological Society 2025;66(2):86-93
Purpose:
We investigated the changes in ocular higher-order aberrations (HOAs) between sutured scleral fixation and modified Yamane sutureless scleral fixation.
Methods:
We retrospectively reviewed 20 patients (20 eyes) who underwent sutured scleral fixation and 22 patients (22 eyes) who underwent modified Yamane sutureless scleral fixation. The best corrected visual acuity (BCVA) and HOAs were measured preoperatively, and at 3 months postoperatively, and the two groups were compared.
Results:
BCVA was significantly improved in both sutured scleral fixation and modified Yamane sutureless scleral fixation (p = 0.038, 0.015, respectively). The internal optic HOAs decreased significantly after scleral fixation both in both groups (p = 0.012, 0.033, respectively). Postoperative internal optic HOAs were significantly higher in modified Yamane sutureless scleral fixation group than in sutured scleral fixation group. (p = 0.034) Postoperative third-order aberrations, coma-like aberrations were significantly higher in modified Yamane sutureless scleral fixation group than in sutured scleral fixation group. (p = 0.032, 0.038, respectively)
Conclusions
Sutured scleral fixation showed more effectively decreased internal optics HOAs. IOL tilt and decentrations correlated with internal HOAs and thus should be avoided particularly in modified Yamane sutureless scleral fixation.

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