1.p66shc deficiency attenuates high glucose-induced autophagy dysfunction in Schwann cells
Su-Jeong CHOI ; Giang-Huong VU ; Harsha NAGAR ; Seonhee KIM ; Ikjun LEE ; Shuyu PIAO ; Byeong Hwa JEON ; Kaikobad IRANI ; Sang-Ha OH ; Cuk-Seong KIM
The Korean Journal of Physiology and Pharmacology 2025;29(1):57-66
Schwann cells are the most abundant cells in the peripheral nervous system, maintaining the development, function and regeneration of peripheral nerves. Defects in these Schwann cells injury response potentially contribute to the pathogenesis of diabetic peripheral neuropathy (DPN), a common complication of diabetes mellitus. The protein p66shc is essential in regulating oxidative stress responses, autophagy induction and cell survival, and is also vital in the development of DPN. In this study, we hypothesized that p66shc mediates high glucose-induced oxidative stress and autophagic dysfunction. In Schwann cells treated with high glucose; p66shc expression, levels of reactive oxygen species, autophagy impairment, and early apoptosis were elevated. Inhibition of p66shc gene expression by siRNA reversed high glucose-induced oxidative stress, autophagy impairment, and early apoptosis. We also demonstrated that the levels of p66shc was increased, while autophagy-related proteins p62 and LC3 (LC3-II/I) were suppressed in the sciatic nerve of streptozotocin-induced diabetes mice. P66shc-deficient mice exhibited the improvement in autophagy impairment after diabetes onset. Our findings suggest that the p66 plays a crucial role in Schwann cell dysfunction, identifying its potential as a therapeutic target.
2.The Korean Organ Transplant Registry (KOTRY): Third Official Adult Heart Transplant Report
Hyo-In CHOI ; Sang Eun LEE ; Junho HYUN ; Darae KIM ; Dong-Ju CHOI ; Eun-Seok JEON ; Hae-Young LEE ; Hyun-Jai CHO ; Hyungseop KIM ; In-Cheol KIM ; Jaewon OH ; Minjae YOON ; Jin Joo PARK ; Jin-Oh CHOI ; Min Ho JU ; Seok-Min KANG ; Soo Yong LEE ; Sung-Ho JUNG ; Jae-Joong KIM
Korean Circulation Journal 2025;55(2):79-96
Background and Objectives:
The Korean Organ Transplant Registry (KOTRY) provided data for this third official report on adult heart transplantation (HT), including information from 709 recipients.
Methods:
Data from HTs performed at seven major centers in Korea between March 2014 and December 2020 were analyzed, focusing on immunosuppression, acute rejection, cardiac allograft vasculopathy (CAV), post-transplant survival, and mechanical circulatory support (MCS) usage.
Results:
The median ages of the recipients and donors were 56.0 and 43.0 years, respectively.Cardiomyopathy and ischemic heart disease were the most common preceding conditions for HT. A significant portion of patients underwent HT at waiting list status 1 and 0. In the multivariate analysis, a predicted heart mass mismatch was associated with a higher risk of 1-year mortality. Patients over 70 years old had a significantly increased risk of 6-year mortality. The risk of CAV was higher for male donors and donors older than 45 years. Acute rejection was more likely in patients with panel reactive antibody levels above 80%, while statin use was associated with a reduced risk. The employment of left ventricular assist device as a bridge to transplantation increased from 2.17% to 22.4%. Pre-transplant extra-corporeal membrane oxygenation was associated with worse post-transplant survival.
Conclusions
In this third KOTRY report, we analyzed changes in the characteristics of adult HT recipients and donors and their impact on post-transplant outcomes. The most notable discovery was the increased use of MCS before HT and their impact on post-transplant outcomes.
3.Multivariable Analysis in Recovery of Mandibular Nerve Disturbance
Ji Yun LEE ; Yoon Joo CHOI ; Kug Jin JEON ; Sang-Sun HAN ; Chena LEE
Journal of Korean Dental Science 2025;18(1):30-38
Objective:
This study aimed to identify factors associated with the recovery of mandibular nerve disturbance and to predict the possibility of recovery tailored to individual patients.
Materials and Methods:
Patients who visited the dental hospital with symptoms of mandibular nerve disturbance from April 2015 to September 2020 were studied. Patients were divided into two groups based on treatment outcomes: recovered or non-recovered. Variables related to recovery included age, sex, onset event of the nerve disturbance, affected area, imaging findings, and treatment methods. The correlation between recovery and these variables was analyzed using the Chi-square test and Fisher’s exact test.
Results:
A total of 328 patients were included in the study.Among the variables associated with recovery, the onset event of the symptom (P-value=0.02) and imaging findings (P-value=0.04) were statistically significant. Among the significant variables, the highest proportion of patients (77.78%) recovered without symptoms of onset event, while implant surgery showed the lowest recovery rate (34.25%). Regarding imaging findings, the recovery rate was highest in cases of suspected canal damage (58.82%), while no patients recovered from compression of the canal (0.00%).
Conclusion
This study highlights the importance of large-scale data analysis and a thorough evaluation of clinical variables to understand mandibular nerve disturbances. The findings provide a basis for improving treatment strategies and reducing the impact of nerve disturbances on patients’ quality of life.
4.Incidence and Temporal Dynamics of Combined Infections in SARS-CoV-2-Infected Patients With Risk Factors for Severe Complications
Sin Young HAM ; Seungjae LEE ; Min-Kyung KIM ; Jaehyun JEON ; Eunyoung LEE ; Subin KIM ; Jae-Phil CHOI ; Hee-Chang JANG ; Sang-Won PARK
Journal of Korean Medical Science 2025;40(11):e38-
Background:
Coronavirus disease 2019 (COVID-19) is a newly emerged infectious disease that needs further clinical investigation. Characterizing the temporal pattern of combined infections in patients with COVID-19 may help clinicians understand the clinical nature of this disease and provide valuable diagnostic and therapeutic guidelines.
Methods:
We retrospectively analyzed COVID-19 patients isolated in four study hospitals in Korea for one year period from May 2021 to April 2022 when the delta and omicron variants were dominant. The temporal characteristics of combined infections based on specific diagnostic tests were analyzed.
Results:
A total of 16,967 COVID-19 patients were screened, 2,432 (14.3%) of whom underwent diagnostic microbiologic tests according to the clinical decision-making, 195 of whom had positive test results, and 0.55% (94/16,967) of whom were ultimately considered to have clinically meaningful combined infections. The median duration for the diagnosis of combined infections was 15 (interquartile range [IQR], 5–25) days after admission. The proportion of community-acquired coinfections (≤ 2 days after admission) was 11.7% (11/94), which included bacteremia (10/94, 10.63%) and tuberculosis (1/94, 1.06%). Combined infections after 2 days of admission were diagnosed at median 16 (IQR, 9–26) days, and included bacteremia (72.3%), fungemia (19.3%), cytomegalovirus (CMV) diseases (8.4%), Pneumocystis jerovecii pneumonia (PJP, 8.4%) and invasive pulmonary aspergillosis (IPA, 4.8%).
Conclusion
Among COVID-19 patients with risk factors for severe complications, 0.55% had laboratory-confirmed combined infections, which included community and nosocomial pathogens in addition to unusual pathogens such as CMV disease, PJP and IPA.
5.Multivariable Analysis in Recovery of Mandibular Nerve Disturbance
Ji Yun LEE ; Yoon Joo CHOI ; Kug Jin JEON ; Sang-Sun HAN ; Chena LEE
Journal of Korean Dental Science 2025;18(1):30-38
Objective:
This study aimed to identify factors associated with the recovery of mandibular nerve disturbance and to predict the possibility of recovery tailored to individual patients.
Materials and Methods:
Patients who visited the dental hospital with symptoms of mandibular nerve disturbance from April 2015 to September 2020 were studied. Patients were divided into two groups based on treatment outcomes: recovered or non-recovered. Variables related to recovery included age, sex, onset event of the nerve disturbance, affected area, imaging findings, and treatment methods. The correlation between recovery and these variables was analyzed using the Chi-square test and Fisher’s exact test.
Results:
A total of 328 patients were included in the study.Among the variables associated with recovery, the onset event of the symptom (P-value=0.02) and imaging findings (P-value=0.04) were statistically significant. Among the significant variables, the highest proportion of patients (77.78%) recovered without symptoms of onset event, while implant surgery showed the lowest recovery rate (34.25%). Regarding imaging findings, the recovery rate was highest in cases of suspected canal damage (58.82%), while no patients recovered from compression of the canal (0.00%).
Conclusion
This study highlights the importance of large-scale data analysis and a thorough evaluation of clinical variables to understand mandibular nerve disturbances. The findings provide a basis for improving treatment strategies and reducing the impact of nerve disturbances on patients’ quality of life.
6.Incidence and Temporal Dynamics of Combined Infections in SARS-CoV-2-Infected Patients With Risk Factors for Severe Complications
Sin Young HAM ; Seungjae LEE ; Min-Kyung KIM ; Jaehyun JEON ; Eunyoung LEE ; Subin KIM ; Jae-Phil CHOI ; Hee-Chang JANG ; Sang-Won PARK
Journal of Korean Medical Science 2025;40(11):e38-
Background:
Coronavirus disease 2019 (COVID-19) is a newly emerged infectious disease that needs further clinical investigation. Characterizing the temporal pattern of combined infections in patients with COVID-19 may help clinicians understand the clinical nature of this disease and provide valuable diagnostic and therapeutic guidelines.
Methods:
We retrospectively analyzed COVID-19 patients isolated in four study hospitals in Korea for one year period from May 2021 to April 2022 when the delta and omicron variants were dominant. The temporal characteristics of combined infections based on specific diagnostic tests were analyzed.
Results:
A total of 16,967 COVID-19 patients were screened, 2,432 (14.3%) of whom underwent diagnostic microbiologic tests according to the clinical decision-making, 195 of whom had positive test results, and 0.55% (94/16,967) of whom were ultimately considered to have clinically meaningful combined infections. The median duration for the diagnosis of combined infections was 15 (interquartile range [IQR], 5–25) days after admission. The proportion of community-acquired coinfections (≤ 2 days after admission) was 11.7% (11/94), which included bacteremia (10/94, 10.63%) and tuberculosis (1/94, 1.06%). Combined infections after 2 days of admission were diagnosed at median 16 (IQR, 9–26) days, and included bacteremia (72.3%), fungemia (19.3%), cytomegalovirus (CMV) diseases (8.4%), Pneumocystis jerovecii pneumonia (PJP, 8.4%) and invasive pulmonary aspergillosis (IPA, 4.8%).
Conclusion
Among COVID-19 patients with risk factors for severe complications, 0.55% had laboratory-confirmed combined infections, which included community and nosocomial pathogens in addition to unusual pathogens such as CMV disease, PJP and IPA.
7.PDK4 expression and tumor aggressiveness in prostate cancer
Eun Hye LEE ; Yun-Sok HA ; Bo Hyun YOON ; Minji JEON ; Dong Jin PARK ; Jiyeon KIM ; Jun-Koo KANG ; Jae-Wook CHUNG ; Bum Soo KIM ; Seock Hwan CHOI ; Hyun Tae KIM ; Tae-Hwan KIM ; Eun Sang YOO ; Tae Gyun KWON
Investigative and Clinical Urology 2025;66(3):227-235
Purpose:
Prostate cancer ranks as the second most common cancer in men globally, representing a significant cause of cancer-related mortality. Metastasis, the spread of cancer cells from the primary site to distant organs, remains a major challenge in managing prostate cancer. Pyruvate dehydrogenase kinase 4 (PDK4) is implicated in the regulation of aerobic glycolysis, emerging as a potential player in various cancers. However, its role in prostate cancer remains unclear. This study aims to analyze PDK4 expression in prostate cancer cells and human samples, and to explore the gene's clinical significance.
Materials and Methods:
PDK4 expression was detected in cell lines and human tissue samples. Migration ability was analyzed using Matrigel-coated invasion chambers. Human samples were obtained from the Kyungpook National University Chilgok Hospital.
Results:
PDK4 expression was elevated in prostate cancer cell lines compared to normal prostate cells, with particularly high levels in DU145 and LnCap cell lines. PDK4 knockdown in these cell lines suppressed their invasion ability, indicating a potential role of PDK4 in prostate cancer metastasis. Furthermore, our results revealed alterations in epithelial-mesenchymal transition markers and downstream signaling molecules following PDK4 suppression, suggesting its involvement in the modulation of invasion-related pathways. Furthermore, PDK4 expression was increased in prostate cancer tissues, especially in castration-resistant prostate cancer, compared to normal prostate tissues, with PSA and PDK4 expression showing a significantly positive correlation.
Conclusions
PDK4 expression in prostate cancer is associated with tumor invasion and castration status. Further validation is needed to demonstrate its effectiveness as a therapeutic target.
8.Post‑transplant cyclophosphamide plus anti‑thymocyte globulin decreased serum IL‑6 levels when compared with post‑transplant cyclophosphamide alone after haploidentical hematopoietic stem cell transplantation
Jeong Suk KOH ; Myung‑Won LEE ; Thi Thuy Duong PHAM ; Bu Yeon HEO ; Suyoung CHOI ; Sang‑Woo LEE ; Wonhyoung SEO ; Sora KANG ; Seul Bi LEE ; Chul Hee KIM ; Hyewon RYU ; Hyuk Soo EUN ; Hyo‑Jin LEE ; Hwan‑Jung YUN ; Deog‑Yeon JO ; Ik‑Chan SONG
Blood Research 2025;60():5-
Background:
Post-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common pro‑ phylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD.Method The clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from Jan‑ uary 2019 to February 2023.
Results:
Forty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II–IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II–IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%; p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%; p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%; p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%; p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038).
Conclusion
Serum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II–IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms of clinical outcomes and complications of HSCT.
9.Radiation-Induced Cavernous Malformation in the Cerebellum:Clinical Features of Two Cases
Hyoung Soo CHOI ; Chae-Yong KIM ; Byung Se CHOI ; Seung Hyuck JEON ; In Ah KIM ; Joo-Young KIM ; Kyu Sang LEE ; Gheeyoung CHOE
Brain Tumor Research and Treatment 2025;13(2):58-64
Radiation-induced cavernous malformations (RICMs) are rare but significant late complications of highdose radiation therapy, particularly in young survivors of brain tumors. This report presents two cases of RICMs following aggressive multimodal treatment, including surgery, chemotherapy, and radiation therapy. Case 1 was a 22-year-old male patient with medulloblastoma treated with craniospinal irradiation, tumor bed boost, and tandem autologous peripheral blood stem cell transplantation. Approximately 8 years after treatment completion, routine follow-up imaging revealed a small focal hemorrhage in the right cerebellum, consistent with an RICM. The lesion was asymptomatic and managed conservatively with regular imaging, showing spontaneous resolution over time, with a significant size reduction noted 9 years post-treatment. Case 2 describes a 32-year-old male with an intracranial germinoma treated with whole-ventricular irradiation. Three years after treatment, the patient developed a symptomatic hemorrhagic RICM near a pre-existing developmental venous anomaly. Surgical resection and Gamma Knife Surgery stabilized the lesion; however, residual symptoms, including tremors and gait disturbances, persisted, affecting the patient’s daily activities. These cases illustrate the diverse clinical courses of RICMs, ranging from spontaneous resolution to the necessity of surgical intervention, and emphasize the importance of long-term surveillance and tailored management strategies for late-onset complications.
10.The Cancer Clinical Library Database (CCLD) from the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) Project
Sangwon LEE ; Yeon Ho CHOI ; Hak Min KIM ; Min Ah HONG ; Phillip PARK ; In Hae KWAK ; Ye Ji KANG ; Kui Son CHOI ; Hyun-Joo KONG ; Hyosung CHA ; Hyun-Jin KIM ; Kwang Sun RYU ; Young Sang JEON ; Hwanhee KIM ; Jip Min JUNG ; Jeong-Soo IM ; Heejung CHAE
Cancer Research and Treatment 2025;57(1):19-27
The common data model (CDM) has found widespread application in healthcare studies, but its utilization in cancer research has been limited. This article describes the development and implementation strategy for Cancer Clinical Library Databases (CCLDs), which are standardized cancer-specific databases established under the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) project by the Korean Ministry of Health and Welfare. Fifteen leading hospitals and fourteen academic associations in Korea are engaged in constructing CCLDs for 10 primary cancer types. For each cancer type-specific CCLD, cancer data experts determine key clinical data items essential for cancer research, standardize these items across cancer types, and create a standardized schema. Comprehensive clinical records covering diagnosis, treatment, and outcomes, with annual updates, are collected for each cancer patient in the target population, and quality control is based on six-sigma standards. To protect patient privacy, CCLDs follow stringent data security guidelines by pseudonymizing personal identification information and operating within a closed analysis environment. Researchers can apply for access to CCLD data through the K-CURE portal, which is subject to Institutional Review Board and Data Review Board approval. The CCLD is considered a pioneering standardized cancer-specific database, significantly representing Korea’s cancer data. It is expected to overcome limitations of previous CDMs and provide a valuable resource for multicenter cancer research in Korea.

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