1.The actual duration of spinal cord stimulator use in patients with complex regional pain syndrome:a Korean nationwide cohort study
In-Ae SONG ; Joon Hee LEE ; Woong Ki HAN ; Francis Sahngun NAHM
The Korean Journal of Pain 2025;38(1):51-57
Background:
Spinal cord stimulators (SCSs) are used to reduce pain and improve quality of life in patients with complex regional pain syndrome (CRPS). However, many patients opt for device removal after SCS implantation due to diminished effect or complications. There is limited research on the actual duration of SCS use in CRPS patients, and no nationwide population-based studies exist. This study aimed to estimate the real-world duration of SCS use in CRPS patients and examine the influencing factors on the duration of SCS use by analyzing the National Healthcare Insurance Database.
Methods:
Adult patients (age ≥ 18) with CRPS who underwent permanent SCS implantation between 2014 and2021 were included. The authors analyzed the median duration of SCS implantation and evaluated the impacts of age, sex, hospital type, and insurance type.
Results:
Of 408 potential patients, 373 patients were included. The median duration of SCS use was 4.4 (95%confidence interval [CI]: 4.0–4.8) years. Male patients retained SCSs longer than female patients (4.7 vs. 4.0 years, P = 0.014), and veterans’ healthcare beneficiaries showed the longest duration of SCS use (median 6.9 [95% CI: 4.6–7.8] years). Age and hospital type did not affect the duration of SCS use (P = 0.381 and P = 0.122, respectively).
Conclusions
The median SCS use duration in CRPS patients was 4.4 years. Considering the high cost and invasiveness of SCS, patients should be informed about the expected duration of SCS use, alongside potential risks and benefits.
2.Fine particulate matter induces osteoclast-mediated bone loss in mice
Hye Young MUN ; Septika PRISMASARI ; Jeong Hee HONG ; Hana LEE ; Doyong KIM ; Han Sung KIM ; Dong Min SHIN ; Jung Yun KANG
The Korean Journal of Physiology and Pharmacology 2025;29(1):9-19
Fine particulate matter (FPM) is a major component of air pollution and has emerged as a significant global health concern owing to its adverse health effects. Previous studies have investigated the correlation between bone health and FPM through cohort or review studies. However, the effects of FPM exposure on bone health are poorly understood. This study aimed to investigate the effects of FPM on bone health and elucidate these effects in vitro and in vivo using mice. Micro-CT analysis in vivo revealed FPM exposure decreased bone mineral density, trabecular bone volume/total volume ratio, and trabecular number in the femurs of mice, while increasing trabecular separation. Histological analysis showed that the FPM-treated group had a reduced trabecular area and an increased number of osteoclasts in the bone tissue. Moreover, in vitro studies revealed that low concentrations of FPM significantly enhanced osteoclast differentiation. These findings further support the notion that short-term FPM exposure negatively impacts bone health, providing a foundation for further research on this topic.
3.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.
4.Toxicity and efficacy study of a combination of two retinoic acids in an ApoE knockout mouse model of atherosclerosis
Da Som JEONG ; Ji-Young LEE ; Hyo-Jeong HAN ; Soo Min KO ; Dong Hyun LEE ; Yerin LEE ; Young-Sik PARK ; Byong-Cheol SHIN ; Woo-Chan SON
The Korean Journal of Physiology and Pharmacology 2025;29(2):179-189
Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE -/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE –/–mice. This study highlights PA9RA's potential as a promising therapeutic agent for atherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.
5.Efficacy of Bone Regeneration Cell Therapy Using Mesenchymal Stem Cells Originating from Embryonic Stem Cells in Animal Models; Bone Defects and Osteomyelitis
Jin-Ho PARK ; Han-Sol BAE ; Ingeun KIM ; Jiwoon JUNG ; Yoonho ROH ; Dongbin LEE ; Tae Sung HWANG ; Hee-Chun LEE ; June-Ho BYUN
Tissue Engineering and Regenerative Medicine 2025;22(1):145-157
BACKGROUND:
Bone defects are commonly encountered due to accidents, diseases, or aging, and the demand for effective bone regeneration, particularly for dental implants, is increasing in our aging society. Mesenchymal stem cells (MSCs) are promising candidates for regenerative therapies; however, obtaining sufficient quantities of these cells for clinical applications remains challenging. DW-MSCs, derived from embryonic stem cells and developed by Daewoong Pharmaceutical, exhibit a robust proliferative capacity even after extensive culture.
METHODS:
This study explores the therapeutic potential of DW-MSCs in various animal models of bone defects. DWMSCs were expanded for over 13 passages for in vivo use in rat and canine models of bone defects and osteomyelitis. The research focused on the in vivo osteogenic differentiation of DW-MSCs, the establishment of a fibrin-based system for bone regeneration, the assessment of bone repair following treatment in animal models, and comparisons with commercially available bone grafts.
RESULTS:
Results showed that DW-MSCs exhibited superior osteogenic differentiation compared to other materials, and the fibrinization process not only preserved but enhanced their proliferation and differentiation capabilities through a 3D culture effect. In both bone defect models, DW-MSCs facilitated significant bone regeneration, reduced inflammatory responses in osteomyelitis, and achieved effective bone healing. The therapeutic outcomes of DW-MSCs were comparable to those of commercial bone grafts but demonstrated qualitatively superior bone tissue restructuring.
CONCLUSION
Our findings suggest that DW-MSCs offer a promising approach for bone regeneration therapies due to their high efficacy and anti-inflammatory properties.
6.Adherence to Pharmacological Management Guidelines for Stable Chronic Obstructive Lung Disease
Sang Min HAN ; Hyo Seon KIM ; Seung Yong PARK ; Heung Bum LEE ; Young Bum PARK ; Chin Kook RHEE ; Youlim KIM ; Seoung Ju PARK
Tuberculosis and Respiratory Diseases 2025;88(2):310-321
Background:
This study evaluated adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and Korean guidelines in the prescription patterns of respiratory specialists for stable chronic obstructive pulmonary disease (COPD) management.
Methods:
Data were collected on medications from 2011 to 2022 using the Korea COPD Subtype Study (KOCOSS) cohort. Patients were divided into two groups: those registered before and after 2019, and we analyzed the percentage of patients meeting the recommended treatment criteria established by each guideline.
Results:
Among 3,477 patients, 85.6% received pharmacological therapy, and 81.6% utilized inhaled medications. Compared to patients enrolled before 2019, there was an increase in inhaler prescriptions among those registered after 2019 (79.7% vs. 86.7%), with dual bronchodilators being the predominant therapy prescribed. Of the patients receiving treatment, 56.9% adhered to the Korean 2018 guideline. Compliance with the GOLD 2019 and GOLD 2023 guidelines was observed in 31.3% and 28.0% of cases, respectively. When analyzing inhaler prescription patterns according to both subgroups and considering the Korean 2018, GOLD 2019, and GOLD 2023 guidelines concurrently, the adherence rates were as follows: (56.6%, 37.8%, 24.0%) and (57.7%, 14.0%, 38.6%).
Conclusion
Adherence rates were higher for the Korean guideline compared to the GOLD recommendations. Furthermore, alignment with both the Korean 2018 and GOLD 2023 guidelines increased among patients enrolled after 2019, compared to those registered earlier. These findings suggest that physicians are modifying their therapeutic strategies to align with both domestic and recent international guidelines.
7.Impact of adding preoperative magnetic resonance imaging to ultrasonography on male breast cancer survival: a matched analysis with female breast cancer
Jeongmin LEE ; Ka Eun KIM ; Myoung Kyoung KIM ; Haejung KIM ; Eun Sook KO ; Eun Young KO ; Boo-Kyung HAN ; Ji Soo CHOI
Ultrasonography 2025;44(1):72-82
Purpose:
The study investigated whether incorporating magnetic resonance imaging (MRI) alongside ultrasonography (US) in the preoperative evaluation is associated with differing survival outcomes between male and female breast cancer patients in a matched analysis. Additionally, clinicopathological prognostic factors were analyzed.
Methods:
Between January 2005 and December 2020, 93 male and 28,191 female patients who underwent breast surgery were screened. Exact matching analysis was conducted for age, pathologic T and N stages, and molecular subtypes. The clinicopathological characteristics and preoperative imaging methods of the matched cohorts were reviewed. Disease-free survival (DFS) and overall survival (OS) were assessed using Kaplan-Meier analysis, and Cox proportional hazards regression analysis was used to identify prognostic factors.
Results:
A total of 328 breast cancer patients (61 men and 267 women) were included in the matched analysis. Male patients had worse DFS (10-year DFS, 70.6% vs. 89.2%; P=0.001) and OS (10-year OS, 64.4% vs. 96.3%; P<0.001) than female patients. The pathologic index cancer size (hazard ratio [HR], 2.013; 95% confidence interval [CI], 1.063 to 3.810; P=0.032) was associated with worse DFS, whereas there were no significant factors associated with OS. Adding MRI to US for preoperative evaluation was not associated with DFS (HR, 1.117; 95% CI, 0.223 to 5.583; P=0.893) or OS (HR, 1.529; 95% CI, 0.300 to 7.781; P=0.609) in male patients.
Conclusion
Adding breast MRI to US in the preoperative evaluation was not associated with survival outcomes in male breast cancer patients, and the pathologic index cancer size was associated with worse DFS.
8.Effect of the Administration of Cautionary Drugs on the Risk of Worsening Myasthenia Gravis:A Retrospective Matched Case-Control Study
Hee Jo HAN ; Seung Woo KIM ; Myeongjee LEE ; Hye Rim KIM ; Yun Ho ROH ; Ha Young SHIN
Yonsei Medical Journal 2025;66(4):218-225
Purpose:
Although some medications trigger the worsening of myasthenia gravis (MG), their clinical influence on patients with MG has not been significantly evaluated. We aimed to investigate whether the risk of clinical worsening of MG increases after administering cautionary drugs in patients with MG.
Materials and Methods:
This retrospective case-control study was based on the medical records of patients diagnosed with MG between 2007 and 2020. We analyzed the risk of MG worsening in patients exposed to cautionary drugs during the risk period, defined as 6 months from the first exposure to cautionary drugs. The risk of MG worsening in the exposed patients was compared to that in the non-exposed patients, who were individually matched in a 1:1 ratio with exposed cases for sex, age, thymoma, and autoantibodies.
Results:
Of the 2002 patients diagnosed with MG, 552 (27.6%) were exposed to cautionary drugs. Neuromuscular blocking agents (320 patients) and beta blockers (66123 person-days) were the most frequently prescribed medications. After exact matching, 220 exposed and 220 non-exposed patients were enrolled. The incidence rate of clinical worsening during the risk period was significantly higher in the exposed patients than in the non-exposed patients (odds ratio=4.09; 95% confidence interval, 1.88–8.90;p<0.001). Clinical worsening was observed in 31 (14.1%) of the exposed patients and in 8 (3.6%) of the non-exposed patients.
Conclusion
The administration of cautionary drugs increased the risk of clinical worsening in patients with MG. Clinicians should be aware of this risk when cautionary drugs need to be administered.
9.Deep Learning-Based Computer-Aided Diagnosis in Coronary Artery Calcium-Scoring CT for Pulmonary Nodule Detection: A Preliminary Study
Seung Yun LEE ; Ji Weon LEE ; Jung Im JUNG ; Kyunghwa HAN ; Suyon CHANG
Yonsei Medical Journal 2025;66(4):240-248
Purpose:
To evaluate the feasibility and utility of deep learning-based computer-aided diagnosis (DL-CAD) for the detection of pulmonary nodules on coronary artery calcium (CAC)-scoring computed tomography (CT).
Materials and Methods:
This retrospective study included 273 patients (aged 63.9±13.2 years; 129 men) who underwent CACscoring CT. A DL-CAD system based on thin-section images was used for pulmonary nodule detection, and two independent junior readers reviewed the standard CAC-scoring CT scans with and without referencing DL-CAD results. A reference standard was established through the consensus of two experienced radiologists. Sensitivity, positive predictive value, and F1-score were assessed on a per-nodule and per-patient basis. The patients’ medical records were monitored until November 2023.
Results:
A total of 269 nodules were identified in 129 patients. With DL-CAD assistance, the readers’ sensitivity significantly improved (65% vs. 80% for reader 1; 82% vs. 86% for reader 2; all p<0.001), without a notable increase in the number of false-positives per case (0.11 vs. 0.13, p=0.078 for reader 1; 0.11 vs. 0.11, p>0.999 for reader 2). Per-patient analysis also enhanced sensitivity with DL-CAD assistance (73% vs. 84%, p<0.001 for reader 1; 89% vs. 91%, p=0.250 for reader 2). During follow-up, lung cancer was diagnosed in four patients (1.5%). Among them, two had lesions detected on CAC-scoring CT, both of which were successfully identified by DL-CAD.
Conclusion
DL-CAD based on thin-section images can assist less experienced readers in detecting pulmonary nodules on CACscoring CT scans, improving detection sensitivity without significantly increasing false-positives.
10.Vitamin D Attenuates Non-Alcoholic Fatty Liver Disease in High-Fat Diet-Induced Obesity Murine Model
Sook In CHUNG ; Lin LIANG ; Heejae HAN ; Kyung Hee PARK ; Jae-Hyun LEE ; Jung-Won PARK
Yonsei Medical Journal 2025;66(2):75-86
Purpose:
Obesity and metabolic syndrome are acknowledged as key factors contributing to the development of non-alcoholic fatty liver disease (NAFLD). Vitamin D (VitD) is a multifaceted secosteroid hormone known for its anti-fibrotic and anti-inflammatory properties, with its deficiency often linked to obesity. Our study aimed to investigate whether VitD supplementation could mitigate the liver pathology associated with NAFLD.
Materials and Methods:
The NAFLD model was developed by subjecting male C57BL/6 mice to a high-fat diet (HFD) for 14 weeks.These mice were supplemented with VitD through intraperitoneal injection at a dosage of 7 μg/kg, administered three times per week for 7 weeks.
Results:
HFD resulted in VitD deficiency, insulin resistance, and increased liver weight. It elevated serum levels of liver aminotransferases and triglyceride, ultimately leading to steatohepatitis with fibrosis. This model exhibited increased levels of transforming growth factor (TGF)-β1, pro-inflammatory cytokines, HNF4α transcription factors, reactive oxygen species (ROS), renin-angiotensin system activity, and epithelial-mesenchymal transitions (EMT) within the liver. Supplementation with VitD resulted in the recovery of liver weight, improvement in histologic features associated with steatohepatitis, and reduction in alanine aminotransferases and triglyceride levels induced by the HFD. Additionally, it mitigated the HFD-induced over-expressions of TGF-β1 and fibrosis-related genes, along with pro-inflammatory cytokines and ROS. Notably, no adverse effect was found due to VitD supplementation in this model.
Conclusion
VitD ameliorates steatohepatitis within obesity-induced NAFLD through its multifaceted pathways. VitD supplementation emerges as a potentially safe, cost-effective, and direct treatment approach for NAFLD patients dealing with obesity or metabolic dysfunction.

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