Background: Transthyretin amyloidosis, a protein-misfolding disorder characterized by systemic amyloid deposition, can be classified as wild-type transthyretin amyloidosis (ATTRwt) or hereditary transthyretin amyloidosis (ATTRv), depending on the presence of transthyretin (TTR) gene variants. We examined the genetic distribution of TTR variants in Korean patients diagnosed with ATTRv. Methods: We retrospectively reviewed 801 participants who underwent TTR analysis at Samsung Medical Center from 2012 to 2024. The participants were categorized into two groups: in-house probands or relatives, and externally referred probands or relatives. Results: Pathogenic or likely pathogenic TTR variants were detected in 36 of 165 in-house probands (21.8%), among which D38A was the most frequent variant (50.0%; 18/36), followed by M13dup and E89K (8.3% each). Among referred probands, D38A was predominant (54.5%; 12/22), followed by M13dup (22.7%; 5/22). Cardiac amyloid involvement was the most common manifestation, observed in 97.2% (35/36) of in-house probands with ATTRv, followed by peripheral nervous system (PNS; 94.4%) and autonomic nervous system (ANS; 88.9%) involvement. In contrast, ANS involvement was most prevalent among in-house relatives who underwent organ evaluation (61.5%; 24/39), followed by cardiac (52.1%; 25/48) and PNS (48.7%; 19/39) involvement. Five of the eight in-house relatives harboring M13dup (62.5%) showed organ involvement, primarily in the ANS, supporting the pathogenicity of this variant. Conclusions This study provides the largest single-institution dataset of Korean patients with ATTRv, incorporating systematic organ assessments. The predominance of the unique TTR variants D38A and M13dup delineates a distinct genetic landscape that may facilitate accurate and timely diagnosis of ATTRv in the Korean population.

A medial closing wedge supramalleolar osteotomy, along with corrections for pes plano-valgus, including medial displacement calcaneal osteotomy, and deltoid ligament repair or reconstruction, is most commonly considered for the joint-preserving surgery of valgus ankle arthritis. In cases of ‘opposing coronal plane deformities,’ however, where the tibial plafond is varus-aligned to the long axis of the tibia and the ground, while the talus is conversely valgus-aligned, medial closing wedge supramalleolar osteotomy may paradoxically risk exacerbating the valgus ankle arthritis. This paper reports the radiological and clinical outcomes of an otherwise healthy, physically active 55-year-old male patient with valgus ankle arthritis and opposing coronal-plane deformities, along with a literature review. The patient underwent joint-preserving surgery consisting of lateral closing wedge supramalleolar osteotomy, fibular osteotomy, medial displacement calcaneal osteotomy, and deltoid ligament augmentation with suture tape. This paper discusses the critical considerations and surgical precautions necessary when deciding on joint-preserving procedures for valgus ankle arthritis.

In forensic medicine, age estimation commonly involves assessing age-related changes in teeth and skeletal structures. Vertebral morphological alterations, such as osteophyte formation, serve as age indicators. Recent studies using deep-learning techniques, such as neural networks, for age estimation from radiographic images have been conducted, reporting significantly higher accuracy than previous studies. This study aimed to estimate age using neural network-based deep-learning techniques applied to computed tomography (CT) cross-sectional images of the spine and evaluate its feasibility. Postmortem CT scans of 214 cadavers with varying decomposition levels were used. Coronal and sagittal cross-sectional images penetrating the center of each vertebral body were extracted for the 11th and 12th thoracic vertebrae and the first to fifth lumbar vertebrae. Using these images, along with the chronological ages of deceased individuals, an age estimation model was developed through regression analysis in PyTorch, employing a convolutional neural networks architecture with five-fold cross-validation. The model achieved a mean absolute error of 5.385 years, root mean squared error of 7.029 years, and coefficient of determination of 0.793. Although the sample size was relatively small, the results suggested the potential applicability of vertebral imagingbased age estimation in the Korean population. Further research using a larger dataset may improve the accuracy and reliability of the model.

Objective: To evaluate the prognostic impact of radiologic and pathologic features in patients with interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF), and to identify the factors associated with the development of progressive pulmonary fibrosis (PPF) and survival. Materials and Methods: This study retrospectively enrolled 75 patients diagnosed with ILD other than IPF who underwent surgical lung biopsy between January 2004 and December 2020. Three chest radiologists independently reviewed the CT features and extent of fibrosis on preoperative and follow-up CT scans. Two pathologists reviewed the histopathological features, including the presence of interstitial pneumonia. The time to PPF and overall survival were estimated using the Kaplan-Meier method. The associations of CT and pathological features with PPF and all-cause mortality were examined using standard Cox regression and time-dependent Cox models, respectively. Results: A total of 75 non-IPF ILD patients (mean age ± standard deviations 56.4 ± 13.2 years; range, 40–88 years) were enrolled. The median follow-up duration was 75.3 months (range, 7.8–189.8 months). Traction bronchiectasis on CT (adjusted hazard ratio [HR], 6.40; P = 0.003) and body mass index (adjusted HR per 1-kg/m2 increase, 0.82; P = 0.002) were found to be significantly associated with PPF in multivariable analysis. Radiological progression (adjusted HR, 18.44;P < 0.001), symptomatic progression (adjusted HR, 4.19; P = 0.011), and age (adjusted HR for 1-year increase, 1.12; P < 0.001) were significantly associated with death. Conclusion Traction bronchiectasis on CT was a significant predictor of PPF, while radiologic and symptomatic progression and older age were associated with poorer survival in patients with ILD other than IPF. These findings indicate that careful radiological evaluation and symptom monitoring may help to predict disease progression and outcomes in patients with nonIPF ILD.

The Wikstroemia genus is highly regarded in traditional Asian medicine for its diverse therapeutic applications, including the treatment of inflammatory and infectious conditions. Among its members,Wikstroemia trichotoma (Thunb.) Makino remains a promising medicinal resource which is yet to be chemicallycharacterized. To ensure the chemical consistency of W. trichotoma, we developed and validated the first HPLC method for the simultaneous quantification of three major marker compounds: chlorogenic acid (1), miconioside B (2), and matteucinol 7-O-apiofuranosyl(1→6)-glucopyranoside (3). Chromatographic separation was achieved on a C18 column using a gradient elution system of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Detection was optimized using a photodiode array (PDA) detector at 280 and 325 nm, based on the absorption maxima of the markers. The method was validated in accordance with the International Council for Harmonisation (ICH) and the Ministry of Food and Drug Safety (MFDS) guidelines. The results demonstrated high linearity (r2 > 0.999), with limits of detection and quantitation ranging from 4.28–6.42 and 12.97–19.47 μg/ mL, respectively. Intra- and inter-day precision (% RSD ≤ 1.83%) and accuracy (recoveries of 92.5–101.7%) were within acceptable limits. Quantitative analysis revealed the contents of 1, 2, and 3 in the W. trichotoma extract to be 19.9, 139.8, and 264.9 mg/g, respectively. This study provides a reliable analytical framework for the standardization, quality control, and future pharmacological evaluation of W. trichotoma.

Purpose: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, necessitating the identification of novel therapeutic targets. The E3 ubiquitin ligase WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) has been implicated in various cancers, yet its specific role and underlying molecular mechanisms in CRC are poorly understood. This study aimed to investigate the functional role of WWP2 in CRC progression and to elucidate its regulatory mechanisms. Methods: WWP2 expression was evaluated in CRC patient tissues and cell lines using immunohistochemistry, quantitative real-time polymerase chain reaction, and western blotting. The biological functions of WWP2 were assessed using in vitro assays for cell proliferation, migration, and invasion following adenovirus-mediated overexpression. The molecular mechanism was investigated by analyzing the protein expression levels of p53 and its downstream target, p21, via western blot. An in vivo xenograft mouse model was used to confirm the oncogenic role of WWP2. Results: WWP2 expression was significantly upregulated in CRC tissues. Overexpression of WWP2 promoted CRC cell proliferation, migration, and invasion. Mechanistically, increased WWP2 expression led to a marked reduction in the protein levels of the tumor suppressor p53. Consequently, the expression of the p53 downstream target, the cell cycle inhibitor p21, was also suppressed. In the xenograft model, WWP2 overexpression significantly enhanced tumor growth. Conclusion Our findings demonstrate that WWP2 functions as an oncogene in CRC. It promotes cancer progression by destabilizing the tumor suppressor p53 and downregulating p21. This study highlights the WWP2-p53-p21 axis as a potential novel therapeutic target for CRC.

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Purpose: The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2023, with international comparisons. Materials and Methods: Cancer incidence, survival, and prevalence rates were calculated using the Korea National Cancer Incidence Database (1999-2023), with survival follow-up until December 31, 2024. Mortality data were obtained from the Ministry of Data and Statistics, while international comparisons were based on GLOBOCAN data. Results: In 2023, 288,613 newly diagnosed cancer cases (age-standardized rate [ASR], 288.6 per 100,000) and 85,271 deaths from cancer (ASR, 64.3 per 100,000) were reported. Among the incident cases, 145,452 (50.4%) were aged 65 years or older. Prostate cancer became the most common cancer among men for the first time. The proportion of localized-stage cancers increased from 45.6% in 2005 to 51.8% in 2023. Korea had the lowest cancer mortality among countries with similar incidence rates and the lowest mortality-to-incidence ratios for stomach, colorectal, and breast cancer. The 5-year relative survival rate (2019-2023) was 73.7% overall and 92.7% for localized-stage cancers. Over 2.73 million prevalent cases were identified in 2023, representing 5.3% of the Korean population. Conclusion These findings indicate that Korea’s cancer control efforts have contributed to early detection and improved survival outcomes. As Korea enters a super-aged society in 2025, cancer burden will continue to increase, requiring sustained and adaptive cancer control strategies.

Purpose: Chronic myeloid leukemia (CML) in children, adolescents, and young adults is rare and differs from older adults. This study evaluated the outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in young Korean CML patients during the tyrosine kinase inhibitor (TKI) era. Materials and Methods: A retrospective analysis of 35 CML patients aged < 40 years who underwent allogeneic HSCT from 2009 to 2019 was conducted using Korean Blood and Marrow Transplantation Registry data. Patients were grouped by age < 20 years at HSCT (group 1, n=15) and 20-40 years at HSCT (group 2, n=20). Survival outcomes including overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) were analyzed using the Kaplan-Meier method. Results: The median time between diagnosis and HSCT was 8.9 months. All the patients achieved engraftment but platelet recovery was significantly slower in group 1 (p=0.034). Acute and chronic graft-versus-host disease occurred in 54.3% and 34.3%, respectively. Five-year OS, RFS, and EFS rates of total patients were 66.8%, 50.8%, and 47.6%, with better OS was observed in group 1 by multivariable analysis (p=0.048). Disease status at HSCT was a significant predictor of OS (p=0.028), RFS (p=0.003), and EFS (p=0.004). Disease progression occurred in 13 out of 35 patients (37.1%); treatment-related mortality accounted for 63.6% of deaths (7 out of 11). Conclusion When performed at a younger age, allogeneic HSCT result in superior outcome in CML. Achieving remission before HSCT is critical for improved outcomes, highlighting the importance of pretransplant remission via optimal TKI strategies and minimal residual disease monitoring.