1.The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers
Ji-Ae LEE ; Hye Eun PARK ; Hye-Yeong JIN ; Lingyan JIN ; Seung Yeon YOO ; Nam-Yun CHO ; Jeong Mo BAE ; Jung Ho KIM ; Gyeong Hoon KANG
Journal of Pathology and Translational Medicine 2025;59(1):50-59
Background:
Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC.
Methods:
Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method.
Results:
CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]).
Conclusions
Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.
2.Effect of Wearing Phospholipid-releasing Contact Lenses on Dry Eyes in Rabbits
Hyeon Jung KIM ; Sehie PARK ; Yun Kyoung RYU ; Jin Sun HWANG ; Sun Hee OH ; Jae Hwi LEE ; Gui Bae KIM ; Young Joo SHIN
Journal of the Korean Ophthalmological Society 2025;66(4):181-190
Purpose:
To investigate whether a new phospholipid-releasing soft contact lens can improve symptoms of dry eyes.
Methods:
The study used 2.5-3.0 kg New Zealand rabbits including both normal non-dry eye rabbits and dry eye rabbits, the latter having undergone electrocauterization of the meibomian glands to block the gland orifices. Each rabbit wore a control contact lens on one eye and a phospholipid-releasing contact lens on the other eye daily. Phospholipid-releasing and control contact lenses were provided by NEOVISION Co., Ltd. The parameters assessed included tear film break-up time, tear osmolarity, ocular surface staining, and central corneal thickness. After the experiment, the rabbits were euthanized and their conjunctival tissue was stained with Periodic Acid Schiff (PAS) to observe conjunctival goblet cells.
Results:
In both dry eye and normal non-dry eye rabbits, tear film break-up time was longer and tear osmolarity was lower when using the phospholipid-releasing contact lens compared to the control contact lens. The ocular surface remained unstained in normal non-dry eye rabbits while staining was observed in dry eye rabbits. There was no significant difference in central corneal thickness between the control and phospholipid-releasing contact lenses in either group. PAS staining showed no difference in conjunctival goblet cell density between the two lens types in normal non-dry eye rabbits. However, in dry eye rabbits, the conjunctival goblet cell density tended to be slightly higher with the phospholipid-releasing contact lens compared to the control lens.
Conclusions
Phospholipid-releasing contact lenses may help reduce dry eye symptoms and minimize contact lens-related complications by stabilizing the tear film and lowering tear osmolarity.
3.Effect of regional COVID-19 outbreak to emergency department response on acute myocardial infarction: a multicenter retrospective study
Young Wook KIM ; Sungbae MOON ; Hyun Wook RYOO ; Jae Yun AHN ; Jung Bae PARK ; Dong Eun LEE ; Sang Hun LEE ; Sangchan JIN ; You Ho MUN ; Jung Ho KIM ; Tae Chang JANG
Journal of the Korean Society of Emergency Medicine 2025;36(2):72-82
Objective:
The Daegu region experienced the first wave of the pandemic at the beginning of the coronavirus disease 2019 (COVID-19) outbreak in Korea. Other non-COVID-19-related treatments during a community outbreak, such as cardiovascular diseases, were expected to impact emergency departments. In acute myocardial infarctions, time is an important factor affecting the patient outcome. This study examined how community COVID-19 outbreak affected STsegment elevated myocardial infarction (STEMI) care in emergency departments.
Methods:
A retrospective analysis was performed on patients visiting five emergency departments in the Daegu area who were diagnosed with STEMI from February 18 to April 17 each year from 2018 to 2020. The demographic characteristics, prehospital variables, in-hospital time variables, and treatment results were collected. The cases were divided into the pre-COVID period and the COVID period for comparison.
Results:
The study included 254 patients (194 pre-COVID, 60 during COVID). The symptom-to-door time did not differ. Although the door-to-first doctor time was shortened (4 min vs. 2 min, P=0.01), the rate of coronary angiogram along with the door-to-angiogram time and the door-to-balloon time did not change. The length of stay in the emergency department was delayed during COVID-19 (median, 136 min vs. 404 min; P<0.01). The in-hospital length of stay and mortality were similar in both groups.
Conclusion
The time to treat STEMI was not delayed significantly during the first wave of the COVID-19 outbreak in the Daegu area compared with the pre-pandemic period. Mortality did not change. The length of stay was elongated significantly in the emergency department but not in the hospital.
4.Tanshinone, a Natural NADPH Oxidase Inhibitor, Mitigates Testosterone-Induced Hair Loss
Yeo Kyu HUR ; Jin Yeong CHAE ; Min Hye CHOI ; Kkotnara PARK ; Da-Woon BAE ; Soo-Bong PARK ; Sun-Shin CHA ; Hye Eun LEE ; In Hye LEE ; Yun Soo BAE
Biomolecules & Therapeutics 2025;33(1):210-220
Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H 2O 2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.
5.Stress Accelerates Depressive-Like Behavior through Increase of SPNS2 Expression in Tg2576 Mice
Seung Sik YOO ; Yuri KIM ; Dong Won LEE ; Hyeon Joo HAM ; Jung Ho PARK ; In Jun YEO ; Ju Young CHANG ; Jaesuk YUN ; Dong Ju SON ; Sang-Bae HAN ; Jin Tae HONG
Biomolecules & Therapeutics 2025;33(3):417-428
To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation.
6.The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers
Ji-Ae LEE ; Hye Eun PARK ; Hye-Yeong JIN ; Lingyan JIN ; Seung Yeon YOO ; Nam-Yun CHO ; Jeong Mo BAE ; Jung Ho KIM ; Gyeong Hoon KANG
Journal of Pathology and Translational Medicine 2025;59(1):50-59
Background:
Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC.
Methods:
Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method.
Results:
CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]).
Conclusions
Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.
7.Amyloid-Related Imaging Abnormalities in Anti-Amyloid Monoclonal Antibody Therapy for Alzheimer’s Disease:Expert Recommendation for Standard MRI Protocol
Jimin KIM ; Eunhee KIM ; Mina PARK ; Yun Jung BAE ; Chong Hyun SUH ; Sung-Hye YOU ; Younghee YIM ; Ho-Joon LEE ; Jin Wook CHOI ; Se Won OH ; Won-Jin MOON ;
Journal of the Korean Society of Radiology 2025;86(1):34-44
The introduction of anti-amyloid therapies for Alzheimer’s disease (AD), such as lecanemab (Lequembi®), which was recently approved in Korea, necessitates careful monitoring for amyloid-related imaging abnormalities (ARIA) using brain MRI. To optimize ARIA monitoring in Korean clinical settings, the Korean Society of Neuroradiology (KSNR) and the Age and Neurodegeneration Imaging (ANDI) Study Group proposed MRI protocol recommendations on essential MR sequences, MRI acquisition parameters, timing and condition of MRI examinations, and essential details to provide a scientific basis for maximizing the safety and efficacy of AD treatment. A customized, standardized MRI protocol focusing on Korea’s healthcare environment can improve ARIA management and ensure patient safety through early detection of potential anti-amyloid therapy side effects, thereby enhancing treatment quality.
8.First report of iron-overload myopathy due to secondary hemochromatosis in a dog
Jae-Hyuk YIM ; Tae-Un KIM ; Woo Jun KIM ; Seulgi BAE ; Sungho YUN ; Su-Min BAEK ; Jin-Kyu PARK
Journal of Veterinary Science 2025;26(1):e3-
and Relevance: Severe necrosis and mild fibrosis were observed in the liver and forelimb skeletal muscles. Based on histological analysis, we diagnosed iron overload myopathy by secondary hemochromatosis. Secondary hemochromatosis with severe muscle atrophy and myositis is very rare, and this is the first report of iron-overload myopathy in a dog.
9.The Effect of Postnatal Systemic Corticosteroid on Neurodevelopmental Outcome in Very Low Birth Weight Preterm Infants
Joo Yun YANG ; Young Min YOUN ; Jung In KANG ; Ye Jin HAN ; Do Kyung LEE ; Hyun Kyung BAE ; So-Yeon SHIM
Neonatal Medicine 2025;32(1):10-20
Purpose:
This study aimed to investigate the effects of postnatal systemic corticosteroids on neurodevelopment in very low birth weight (VLBW) preterm infants.
Methods:
This was a population-based study of the Korean Neonatal Network of VLBW infant born at 23+0 and 31+6 weeks of gestation between 2013 and 2020. VLBW preterm infants assessed using the Bayley Scales of Infant and Toddler Development, third edition (BSID-III) at 18–24 months of corrected age and 3 years of age were enrolled. The primary outcomes were BSID-III scores and neurodevelopmental delays, with scores of <85. Socioeconomic status and clinical variables were adjusted for using multivariate regression analyses.
Results:
In total, 517 infants were enrolled in this study. Among the 216 (41.8%) infants who received postnatal systemic corticosteroids, the rate of cognitive delay was significantly higher at 18–24 months of corrected age than at 3 years of age. The rates of language and motor delays were significantly higher both at 18–24 months of corrected age and at 3 years of age. When multivariate logistic regression was performed, postnatal systemic corticosteroid use was significantly associated with cognitive delay at 18–24 months of corrected age, but not at 3 years of age. There was no significant association between postnatal systemic corticosteroid use and language or motor delay at 18-24 months of corrected age or at 3 years of age after multivariate logistic regression.
Conclusion
Postnatal systemic corticosteroid use in VLBW preterm infants increased the risk of cognitive delay at 18–24 months of corrected age, but not at 3 years.
10.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.

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