1.Activatable PROTAC nanoassembly for photodynamic PTP1B proteolysis enhances glioblastoma immunotherapy.
Yeongji JANG ; Jiwoong CHOI ; Byeongmin PARK ; Jung Yeon PARK ; Jae-Hyeon LEE ; Jagyeong GOO ; Dongwon SHIN ; Sun Hwa KIM ; Yongju KIM ; Hyun Kyu SONG ; Jooho PARK ; Kwangmeyung KIM ; Yoosoo YANG ; Man Kyu SHIM
Acta Pharmaceutica Sinica B 2025;15(9):4886-4899
In light of the burgeoning successes of cancer immunotherapy, glioblastoma (GBM) remains refractory due to an immunosuppressive microenvironment originating from its molecular heterogeneity. Thus, identifying promising therapeutic targets for treating GBM and discovering methodologies to effectively regulate them is still a tremendous challenge. Here we describe photodynamic protein tyrosine phosphatase 1B (PTP1B) proteolysis mediated by a proteolysis-targeting chimera (PROTAC) nanoassembly. The PTP1B-targeting PROTAC is conjugated with a photosensitizer via a cathepsin B (Cat B)-cleavable peptide, which spontaneously forms nanoassemblies due to intermolecular π-π stacking interactions. In GBM models, PROTAC nanoassemblies significantly accumulate in the tumor region across the disrupted blood-brain barrier (BBB), triggering a burst release of the photosensitizer and active PROTAC by Cat B-mediated enzymatic cleavage. Upon laser irradiation, photodynamic therapy (PDT) synergizes with PROTAC-mediated PTP1B proteolysis to induce potent immunogenic cell death (ICD) in tumor cells. Subsequently, persistent PTP1B degradation by nanoassemblies in Cat B-overexpressed intratumoral T cells downregulates exhaustion markers, reinvigorating their functionality. These sequential processes of photodynamic PTP1B proteolysis ultimately augment T cell-mediated antitumor immunity as well as protective immunity, completely eradicating the primary GBM and preventing its recurrence. Overall, our findings underscore the therapeutic potential of combining PDT with PROTAC activity for GBM immunotherapy.
3.Development of automatic organ segmentation based on positron-emission tomography analysis system using Swin UNETR in breast cancer patients in Korea
Dong Hyeok CHOI ; Joonil HWANG ; Hai-Jeon YOON ; So Hyun AHN
The Ewha Medical Journal 2025;48(2):e30-
Purpose:
The standardized uptake value (SUV) is a key quantitative index in nuclear medicine imaging; however, variations in region‐of‐interest (ROI) determination exist across institutions. This study aims to standardize SUV evaluation by introducing a deep learning‐based quantitative analysis method that enhances diagnostic and prognostic accuracy.
Methods:
We used the Swin UNETR model to automatically segment key organs (breast, liver, spleen, and bone marrow) critical for breast cancer prognosis. Tumor segmentation was performed iteratively based on predefined SUV thresholds, and prognostic information was extracted from the liver, spleen, and bone marrow (reticuloendothelial system). The artificial intelligence training process employed 3 datasets: a test dataset (40 patients), a validation dataset (10 patients), and an independent test dataset (10 patients). To validate our approach, we compared the SUV values obtained using our method with those produced by commercial software.
Results:
In a dataset of 10 patients, our method achieved an auto‐segmentation accuracy of 0.9311 for all target organs. Comparison of maximum SUV and mean SUV values from our automated segmentation with those from traditional single‐ROI methods revealed differences of 0.19 and 0.16, respectively, demonstrating improved reliability and accuracy in whole‐organ SUV analysis.
Conclusion
This study successfully standardized SUV calculation in nuclear medicine imaging through deep learning‐based automated organ segmentation and SUV analysis, significantly enhancing accuracy in predicting breast cancer prognosis.
4.Environmental disease monitoring by regional Environmental Health Centers in Korea: a narrative review
Myung-Sook PARK ; Hwan-Cheol KIM ; Woo Jin KIM ; Yun-Chul HONG ; Won-Jun CHOI ; Seock-Yeon HWANG ; Jiho LEE ; Young-Seoub HONG ; Yong-Dae KIM ; Seong-Chul HONG ; Joo Hyun SUNG ; Inchul JEONG ; Kwan LEE ; Won-Ju PARK ; Hyun-Joo BAE ; Seong-Yong YOON ; Cheolmin LEE ; Kyoung Sook JEONG ; Sanghyuk BAE ; Jinhee CHOI ; Ho-Hyun KIM
The Ewha Medical Journal 2025;48(1):e3-
This study explores the development, roles, and key initiatives of the Regional Environmental Health Centers in Korea, detailing their evolution through four distinct phases and their impact on environmental health policy and local governance. It chronicles the establishment and transformation of these centers from their inception in May 2007, through four developmental stages. Originally named Environmental Disease Research Centers, they were subsequently renamed Environmental Health Centers following legislative changes. The analysis includes the expansion in the number of centers, the transfer of responsibilities to local governments, and the launch of significant projects such as the Korean Children’s Environmental Health Study (Ko-CHENS ). During the initial phase (May 2007–February 2009), the 10 centers concentrated on research-driven activities, shifting from a media-centered to a receptor-centered approach. In the second phase, prompted by the enactment of the Environmental Health Act, six additional centers were established, broadening their scope to address national environmental health issues. The third phase introduced Ko-CHENS, a 20-year national cohort project designed to influence environmental health policy by integrating research findings into policy frameworks. The fourth phase marked a decentralization of authority, empowering local governments and redefining the centers' roles to focus on regional environmental health challenges. The Regional Environmental Health Centers have significantly evolved and now play a crucial role in addressing local environmental health issues and supporting local government policies. Their capacity to adapt and respond to region-specific challenges is essential for the effective implementation of environmental health policies, reflecting geographical, socioeconomic, and demographic differences.
5.Prevalence and factors influencing postpartum depression and its culture-specific cutoffs for women in Asia: a scoping review
Bora MOON ; Hyun Kyoung KIM ; Ju-Hee NHO ; Hyunkyung CHOI ; ChaeWeon CHUNG ; Sook Jung KANG ; Ju Hee KIM ; Ju-Young LEE ; Sihyun PARK ; Gisoo SHIN ; Ju-Eun SONG ; Min Hee LEE ; Sue KIM
The Ewha Medical Journal 2025;48(1):e15-
The prevalence of postpartum depression (PPD) in Asia is reported to range from 13.53% to 22.31%. However, there remains a gap in the identification of PPD, particularly regarding cultural cutoff points. Therefore, the purpose of this scoping review was to determine the prevalence and associated factors of PPD in Eastern, South-eastern, Western, and Southern Asian countries and analyze the cutoff points of the Edinburgh Postnatal Depression Scale (EPDS) used across these countries. Following Arksey and O'Malley’s five-step scoping review framework, the population was defined as mothers, the concept as the EPDS, and the context as the Asian region. A literature search was conducted using PubMed, Embase, CINAHL, PsycINFO, and Web of Science. The data analysis focused on demographic characteristics, EPDS cutoffs and features, PPD prevalence, and its associated factors. Nineteen studies were selected. Most countries used translated versions of the EPDS with demonstrated reliability and validity. The cutoff scores varied, with most using scores of 10 or higher. The prevalence of PPD ranged from 5.1% to 78.7%. Key associated factors for PPD included cultural factors such as relationships with in-laws and preferences for the newborn’s sex. To improve the accuracy of PPD screening in Asia, the EPDS should be used consistently, and appropriate cutoff criteria must be established. In addition, prevention strategies and programs that reflect the cultural characteristics and social context of Asia need to be developed for the early detection and prevention of PPD.
6.Primary Cholangiocarcinoma of the Liver Presenting as a Complicated Hepatic Cyst: A Diagnostic Challenge
Chang Won HA ; Sang Deok SHIN ; Myung Ji GOH ; Byeong Geun SONG ; Wonseok KANG ; Dong Hyun SINN ; Geum-Youn GWAK ; Yong-Han PAIK ; Moon Seok CHOI ; Joon Hyeok LEE
The Korean Journal of Gastroenterology 2025;85(1):83-88
Primary cholangiocarcinoma is a rare bile duct epithelial neoplasm that can present with atypical clinical manifestations, complicating its diagnosis. A 62-year-old male showed symptoms suggestive of a complicated hepatic cyst that was later identified as intrahepatic cholangiocarcinoma. The patient presented with abdominal discomfort without fever. Imaging revealed a large cystic lesion in the liver. Despite the initial treatment for a presumed abscess, a biopsy confirmed cholangiocarcinoma. This case highlights the diagnostic challenge of distinguishing between benign complicated hepatic cysts and malignancies, particularly when typical markers of infection are absent. Early biopsy and vigilant assessments are crucial in such presentations to avoid a delayed diagnosis and initiate appropriate treatment.
7.Miliary Tuberculosis Initially Presenting as an Isolated Hepatic Abscess
Chang Won HA ; Sang Deok SHIN ; Myung Ji GOH ; Byeong Geun SONG ; Wonseok KANG ; Dong Hyun SINN ; Geum-Youn GWAK ; Yong-Han PAIK ; Moon Seok CHOI ; Joon Hyeok LEE
The Korean Journal of Gastroenterology 2025;85(1):78-82
Hepatic tuberculosis, typically associated with miliary tuberculosis, can occasionally present as localized liver lesions. This case report describes a 77-year-old male presenting with persistent abdominal pain and fever, following an endoscopic retrograde cholangiopancreatography for bile duct sludge removal. Subsequent computed tomography revealed focal liver lesions. Despite initial treatment with antibiotics for a suspected inflammatory liver abscess, his condition did not improve. A liver biopsy was performed, revealing caseous granulomas, and the tuberculosis polymerase chain reaction result was positive. The patient was diagnosed with primary hepatic tuberculosis, which later disseminated. Oral anti-tuberculosis therapy was initiated and is currently being closely monitored. This case emphasizes the importance of considering hepatic tuberculosis in the differential diagnosis of liver lesions, particularly in cases involving cholestatic liver function tests, and persistent symptoms unresponsive to conventional antibiotics.
8.Increased risk of dementia in patients with primary Sjogren’s syndrome: a nationwide population-based cohort study
Kyung-Ann LEE ; Hyeji JEON ; Hyun-Sook KIM ; Kyomin CHOI ; Gi Hyeon SEO
The Korean Journal of Internal Medicine 2025;40(2):330-338
Background/Aims:
This nationwide cohort study aimed to evaluate (1) whether primary Sjogren’s syndrome (pSS) can contribute to the development of dementia and (2) whether the use of hydroxychloroquine (HCQ) can decrease the incidence of dementia in patients with pSS using the Health Insurance Review and Assessment database.
Methods:
We established a cohort between 2008 and 2020 of 20,160 patients with pSS without a history of dementia. The control group comprised sex- and age-matched individuals with no history of autoimmune disease or dementia. Cox proportional hazard analyses were performed to identify the association between pSS and dementia development. We also assessed the hazard ratio (HR) of dementia in early users of HCQ (within 180 days of the diagnosis of pSS) compared to non-users, adjusted for age, sex, and comorbidities.
Results:
The incidence of dementia was 0.68 (95% CI 0.64–0.72) cases per 100 person-years in pSS, and it was 0.58 (0.56–0.60) in the controls. The adjusted HR (aHR) of developing dementia was 1.16 (1.09–1.25) times greater in the pSS group than in the controls. The risk of dementia did not increase in HCQ users (aHR 1.07 [0.94–1.21]), but HCQ non-users had a 1.22 (1.12–1.33) higher risk of developing dementia than the matched controls. The use of HCQ lowered the risk of dementia in comparison with non-users in patients with pSS (aHR 0.82 [0.71–0.94]).
Conclusions
Our results suggest that pSS is associated with an increased risk of dementia. HCQ may prevent dementia in patients with pSS.
9.Initial and peak serum levels of Krebs von den Lungen-6 for predicting the prognosis of patients with COVID-19
Geonui KIM ; Hyeonwoo KWON ; Sang Hyun RA ; Euijin CHANG ; Seongman BAE ; Jiwon JUNG ; Min Jae KIM ; Yong Pil CHONG ; Sang-Oh LEE ; Sang-Ho CHOI ; Yang Soo KIM ; Sung-Han KIM
The Korean Journal of Internal Medicine 2025;40(2):321-329
Background/Aims:
Krebs von den Lungen-6 (KL-6) is associated with prognosis in patients with COVID-19. However, there is limited data on the correlation between the prognosis of COVID-19 and varying KL-6 levels at different time points. We investigated the optimal cutoff values of the initial and peak serum KL-6 levels to predict mortality and evaluated their correlation with mortality.
Methods:
This retrospective cohort study collected data on serially collected serum KL-6 levels in patients hospitalized with COVID-19 between October 2020 and January 2022 at a single tertiary hospital in South Korea. The area under the receiver operating characteristic curve and Youden index were used to determine the cutoff points for the initial and peak KL-6 levels that best predicted 30-day mortality. The association between the initial and peak KL-6 values was assessed by univariate and multivariate logistic regression models.
Results:
A total of 349 patients were included in this study. The mean initial and peak KL-6 levels were significantly higher in the non-survivor group than in the survivor group. The initial and peak KL-6 values that best predicted 30-day mortality were 491.85 U/mL and 660.05 U/mL, respectively. An initial KL-6 level greater than 491.85 U/mL and a peak KL-6 level greater than 660.05 U/mL were significantly associated with 30-day mortality.
Conclusions
The initial and peak levels of KL-6 were significantly associated with 30-day mortality in hospitalized patients with COVID-19. These findings suggest that serially monitoring blood KL-6 levels could be a valuable prognostic indicator for COVID-19.
10.Short-term effects of PCSK-9 inhibitors on percutaneous coronary intervention in patients with acute coronary syndrome
Dong Hyun GIM ; In Young CHOI ; Young-Jae KI ; Hyun Kuk KIM ; Sung Soo KIM ; Keun-Ho PARK ; Heesang SONG ; Dong-Hyun CHOI
The Korean Journal of Internal Medicine 2025;40(3):438-448
Background/Aims:
Proprotein-converting enzyme subtilisin-kexin type 9 (PCSK9) inhibitors act more promptly and efficiently than statins and reduce the risk of cardiovascular events in patients with acute coronary syndrome (ACS). This study aimed to assess the short-term effects of perioperative administration of a single-dose PCSK9 inhibitor in patients with ACS.
Methods:
This study included 789 consecutive patients undergoing percutaneous coronary intervention (PCI) for ACS. The primary clinical endpoint was the occurrence of major adverse cardiovascular events (MACEs) within one month, including cardiac death, non-fatal myocardial infarction, unanticipated revascularization, stroke, stent thrombosis, and rehospitalization for ischemic causes or heart failure.
Results:
PCSK9 inhibitors were administered to 201 of 789 patients. MACEs occurred in eight patients (4.0%) in the treated group and 60 patients (10.2%) in the non-treated group for one month (hazard ratio 0.38, 95% confidence interval 0.18 to 0.80, p = 0.010). The benefit of PCSK9 inhibitors in terms of MACEs was greater in the subgroup of patients treated more than 1 hour before PCI than in the subgroup treated less than 1 hour before PCI or treated after PCI and in the non-treated group.
Conclusions
In patients undergoing PCI for ACS, the risk of MACEs was lower in those treated with perioperative single-dose PCSK9 inhibitors than in those in the untreated group. This benefit was especially noticeable in the subgroups treated > 1 hour before PCI than in those treated less than 1 hour before PCI or after PCI, regardless of the clinical presentation of ACS.

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