1.Mechanism of Ruyan Neixiao Cream in Promoting Ferroptosis in Breast Precancerous Lesion Cells by Regulating Nrf2/SLC7A11/GPX4 Signaling Pathway
Haotian ZHANG ; Yebei QIU ; Ran SU ; Xianxin YAN ; Min MA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):98-107
ObjectiveTo explore the mechanism by which Ruyan Neixiao cream (RUC) induces ferroptosis in breast precancerous lesion (BPL) cells, and to enrich the theoretical foundation for its use in the treatment of BPL. MethodsThe inhibition of cell proliferation by 1%, 2%, and 4% concentrations of Ruyanneixiao Cream transdermal solution (RUT) was assessed using cell counting kit-8 (CCK-8) and a colony formation assay. Reactive oxygen species (ROS) were measured using the DCFH-DA probe, and the levels of ferrous ions (Fe2+), glutathione (GSH), and malondialdehyde (MDA) were determined using appropriate kits. Lipid peroxidation was detected with the C11-BODIPY581/591 fluorescent probe. The expression of nuclear factor E2-related factor 2 (Nrf2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) proteins was analyzed by Western blot. The BPL rat model was constructed using 2,2′-bis(hydroxymethyl)butyric acid (DMBA) combined with estrogen and progesterone, and the rats were treated with RUC for external application. After the 12th cycle, the rats were euthanized, and histopathological changes in breast tissue were observed by hematoxylin-eosin (HE) staining. Fe2+ and MDA levels in breast tissue were measured using corresponding kits. The expression of Nrf2, SLC7A11, and GPX4 proteins in BPL rat breast tissue was detected by immunohistochemistry (IHC) and Western blot. ResultsCompared with the matrix group, the cell viability of MCF-10AT cells in the 1%, 2%, and 4% RUT groups was significantly reduced (P<0.05) in a concentration-dependent manner, with the 24-hour half inhibitory concentration (IC50) being 2.23%. Compared with the 4% RUT group, cell viability in the RUT + Fer-1 group was significantly increased (P<0.05). Compared with the matrix group, the colony formation rates of MCF-10AT cells in the 1%, 2%, and 4% RUT groups were significantly decreased (P<0.05). Compared with the 4% RUT group, the cell colony formation rate of the RUT + Fer-1 group was significantly increased (P<0.05). Compared with the matrix group, the levels of ROS and Fe2+ in the 1%, 2%, and 4% RUT groups were significantly increased (P<0.05), while GSH levels were significantly decreased (P<0.05), and MDA and lipid peroxidation levels were significantly increased (P<0.05). Compared with the 4% RUT group, ROS and Fe2+ levels in the RUT + Fer-1 group were significantly reduced (P<0.05), while GSH levels were significantly increased (P<0.05), and MDA and lipid peroxidation levels were significantly reduced (P<0.05). Compared with the matrix group, the protein expression levels of Nrf2, SLC7A11, and GPX4 in the 1%, 2%, and 4% RUT groups were significantly decreased (P<0.05). Compared with the 4% RUT group, the protein expression levels of Nrf2, SLC7A11, and GPX4 in the RUT + Fer-1 group were significantly increased (P<0.05). In the in vivo experiment, compared with the matrix group, the breast tissue histopathological status of the BPL rats in the RUC group was effectively improved, with less dilatation of the mammary ducts and more orderly duct arrangement. No pathological morphology indicative of invasive cancer was observed. Compared with the matrix group, Fe2+ and MDA levels in the mammary tissue of the RUC group were significantly increased (P<0.05). Compared with the matrix group, the protein expression levels of Nrf2, SLC7A11, and GPX4 in the mammary tissue of the RUC group were significantly reduced (P<0.05). ConclusionRUC may induce ferroptosis in BPL cells by inhibiting the Nrf2/SLC7A11/GPX4 signaling pathway, increasing Fe2+ accumulation, and promoting lipid peroxidation.
2.Mechanism of Ruyan Neixiao Cream in Promoting Ferroptosis in Breast Precancerous Lesion Cells by Regulating Nrf2/SLC7A11/GPX4 Signaling Pathway
Haotian ZHANG ; Yebei QIU ; Ran SU ; Xianxin YAN ; Min MA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):98-107
ObjectiveTo explore the mechanism by which Ruyan Neixiao cream (RUC) induces ferroptosis in breast precancerous lesion (BPL) cells, and to enrich the theoretical foundation for its use in the treatment of BPL. MethodsThe inhibition of cell proliferation by 1%, 2%, and 4% concentrations of Ruyanneixiao Cream transdermal solution (RUT) was assessed using cell counting kit-8 (CCK-8) and a colony formation assay. Reactive oxygen species (ROS) were measured using the DCFH-DA probe, and the levels of ferrous ions (Fe2+), glutathione (GSH), and malondialdehyde (MDA) were determined using appropriate kits. Lipid peroxidation was detected with the C11-BODIPY581/591 fluorescent probe. The expression of nuclear factor E2-related factor 2 (Nrf2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) proteins was analyzed by Western blot. The BPL rat model was constructed using 2,2′-bis(hydroxymethyl)butyric acid (DMBA) combined with estrogen and progesterone, and the rats were treated with RUC for external application. After the 12th cycle, the rats were euthanized, and histopathological changes in breast tissue were observed by hematoxylin-eosin (HE) staining. Fe2+ and MDA levels in breast tissue were measured using corresponding kits. The expression of Nrf2, SLC7A11, and GPX4 proteins in BPL rat breast tissue was detected by immunohistochemistry (IHC) and Western blot. ResultsCompared with the matrix group, the cell viability of MCF-10AT cells in the 1%, 2%, and 4% RUT groups was significantly reduced (P<0.05) in a concentration-dependent manner, with the 24-hour half inhibitory concentration (IC50) being 2.23%. Compared with the 4% RUT group, cell viability in the RUT + Fer-1 group was significantly increased (P<0.05). Compared with the matrix group, the colony formation rates of MCF-10AT cells in the 1%, 2%, and 4% RUT groups were significantly decreased (P<0.05). Compared with the 4% RUT group, the cell colony formation rate of the RUT + Fer-1 group was significantly increased (P<0.05). Compared with the matrix group, the levels of ROS and Fe2+ in the 1%, 2%, and 4% RUT groups were significantly increased (P<0.05), while GSH levels were significantly decreased (P<0.05), and MDA and lipid peroxidation levels were significantly increased (P<0.05). Compared with the 4% RUT group, ROS and Fe2+ levels in the RUT + Fer-1 group were significantly reduced (P<0.05), while GSH levels were significantly increased (P<0.05), and MDA and lipid peroxidation levels were significantly reduced (P<0.05). Compared with the matrix group, the protein expression levels of Nrf2, SLC7A11, and GPX4 in the 1%, 2%, and 4% RUT groups were significantly decreased (P<0.05). Compared with the 4% RUT group, the protein expression levels of Nrf2, SLC7A11, and GPX4 in the RUT + Fer-1 group were significantly increased (P<0.05). In the in vivo experiment, compared with the matrix group, the breast tissue histopathological status of the BPL rats in the RUC group was effectively improved, with less dilatation of the mammary ducts and more orderly duct arrangement. No pathological morphology indicative of invasive cancer was observed. Compared with the matrix group, Fe2+ and MDA levels in the mammary tissue of the RUC group were significantly increased (P<0.05). Compared with the matrix group, the protein expression levels of Nrf2, SLC7A11, and GPX4 in the mammary tissue of the RUC group were significantly reduced (P<0.05). ConclusionRUC may induce ferroptosis in BPL cells by inhibiting the Nrf2/SLC7A11/GPX4 signaling pathway, increasing Fe2+ accumulation, and promoting lipid peroxidation.
3.Analyzing the occupational health literacy level and its influencing factors among workers in non-metallic mineral product industry in Yunfu City
Xiaoyue CHEN ; Xiaotang SU ; Jiabin CHEN ; Min YANG ; Huiqing CHEN ; Xiaoyi LI ; Jichao CHEN
China Occupational Medicine 2025;52(1):94-98
Objective To analyze the occupational health literacy (OHL) level and its influencing factors of workers in non-metallic mineral product industry in Yunfu City. Methods A total of 947 frontline workers from 24 non-metallic mineral products enterprises in Yunfu City were selected as the research subjects using the stratified random sampling method. The OHL level of the workers were assessed using the Occupational Health Literacy Questionnaire of National Key Populations. Results The overall OHL level of the research subjects was 58.3% (552/947). The OHL levels across four dimensions, from highest to lowest, were basic knowledge of occupational health protection (94.7%), healthy work practices and behaviors (81.8%), legal knowledge of occupational health (65.5%), and basic skills of occupational health protection (25.9%). The results of binary logistic regression analysis showed that workers with 2.0-<10.0 years and ≥10 years of work experience had higher OHL levels than those with <2.0 years of work experience (all P<0.01). Workers with a high school education or above had higher OHL levels than those with a junior high school education or below (all P<0.01). Workers in large- and medium-sized enterprises had higher OHL levels than those in small and micro-sized enterprises (both P<0.01). Conclusion The OHL levels of workers in Yunfu City's non-metallic mineral products industry can be further improved, particularly the occupational health protection skills and related legal knowledge. Workers with short seniority, low educational level, and in small and micro enterprises should be the key groups for improving OHL levels.
4.Observer-Blind Randomized Control Trial for the Effectiveness of Intensive Case Management in Seoul: Clinical and Quality-of-Life Outcomes for Severe Mental Illness
Hye-Young MIN ; Seung-Hee AHN ; Jeung Suk LIM ; Hwa Yeon SEO ; Sung Joon CHO ; Seung Yeon LEE ; Dohhee KIM ; Kihoon YOU ; Hyun Seo CHOI ; Su-Jin YANG ; Jee Eun PARK ; Bong Jin HAHM ; Hae Woo LEE ; Jee Hoon SOHN
Psychiatry Investigation 2025;22(5):513-521
Objective:
In South Korea, there is a significant gap in systematic, evidence-based research on intensive case management (ICM) for individuals with severe mental illness (SMI). This study aims to evaluate the effectiveness of ICM through a randomized controlled trial (RCT) comparing ICM with standard case management (non-ICM).
Methods:
An RCT was conducted to assess the effectiveness of Seoul-intensive case management (S-ICM) vs. non-ICM in individuals with SMI in Seoul. A total of 78 participants were randomly assigned to either the S-ICM group (n=41) or the control group (n=37). Various clinical assessments, including the Brief Psychiatric Rating Scale (BPRS), Montgomery–Åsberg Depression Rating Scale, Health of the Nation Outcome Scale, and Clinical Global Impression-Improvement (CGI-I), along with quality-of-life measures such as the WHO Disability Assessment Schedule, WHO Quality of Life scale, and Multidimensional Scale of Perceived Social Support (MSPSS) were evaluated over a 3-month period. Statistical analyses, including analysis of covariance and logistic regression, were used to determine the effectiveness of S-ICM.
Results:
The S-ICM group had significantly lower odds of self-harm or suicidal attempts compared to the control group (adjusted odds ratio [aOR]=0.30, 95% confidence interval [CI]: 0.21–1.38). Psychiatric symptoms measured by the BPRS and perceived social support measured by the MSPSS significantly improved in the S-ICM group. The S-ICM group also had significantly higher odds of CGI-I compared to the control group (aOR=8.20, 95% CI: 2.66–25.32).
Conclusion
This study provides inaugural evidence on the effectiveness of S-ICM services, supporting their standardization and potential nationwide expansion.
6.Characteristics and outcomes of portal vein thrombosis in patients with inflammatory bowel disease in Korea
Ki Jin KIM ; Su-Bin SONG ; Jung-Bin PARK ; June Hwa BAE ; Ji Eun BAEK ; Ga Hee KIM ; Min-Jun KIM ; Seung Wook HONG ; Sung Wook HWANG ; Dong-Hoon YANG ; Byong Duk YE ; Jeong-Sik BYEON ; Seung-Jae MYUNG ; Suk-Kyun YANG ; Chang Sik YU ; Yong-Sik YOON ; Jong-Lyul LEE ; Min Hyun KIM ; Ho-Su LEE ; Sang Hyoung PARK
The Korean Journal of Internal Medicine 2025;40(2):243-250
Background/Aims:
Portal vein thrombosis (PVT) frequently occurs in patients with inflammatory bowel disease (IBD), particularly when influenced by factors such as abdominal infections, IBD flare-ups, or surgical procedures. The implications of PVT range from immediate issues such as intestinal ischemia to long-term concerns including portal hypertension and its complications. However, there is a notable gap in comprehensive studies on PVT in IBD, especially with the increasing incidence of IBD in Asia. This research aimed to evaluate the clinical features and outcomes of PVT in patients with IBD at a leading hospital in South Korea.
Methods:
This retrospective analysis reviewed adult patients diagnosed with both IBD and PVT from 1989 to 2021 at a renowned South Korean medical center. The study focused on patient characteristics, specifics of PVT, administered treatments, and outcomes, all confirmed through enhanced CT scans.
Results:
A total of 78 patients met the study’s criteria. Notably, only 20.5% (16/78) were treated with oral anticoagulants; however, a vast majority (96.2%; 75/78) achieved complete radiographic resolution (CRR). When comparing patients receiving anticoagulants to those who did not, a significant preference for anticoagulant use was observed in cases where the main portal vein was affected, as opposed to just the left or right veins (p = 0.006). However, multivariable analysis indicated that neither anticoagulant use nor previous surgeries significantly impacted CRR.
Conclusions
Patients with IBD and PVT generally had favorable outcomes, regardless of anticoagulant use.
7.Potential of histone deacetylase 6 inhibitors in alleviating chemotherapy-induced peripheral neuropathy
Su Jung PARK ; Soung-Min LEE ; Seong Mook KANG ; Hyun-Mo YANG ; Su-Kil SEO ; Ju-Hee LEE
The Korean Journal of Pain 2025;38(2):152-162
Background:
Histone deacetylase 6 (HDAC6), belonging to class IIb of histone deacetylases, regulates theacetylation of the cytoplasmic protein α-tubulin. The overexpression of HDAC6 is linked to the development oftumors, and inhibiting HDAC6 is known to trigger apoptosis in multiple myeloma cells. In addition to its application in cancer treatment, bortezomib, a proteasome inhibitor, is widely used in managing multiple myeloma and has shown effectiveness in patients with both newly diagnosed and relapsed disease. However, the treatment regimen may be delayed or discontinued due to the risk of peripheral neuropathy, a significant non-hematologic side effect.
Methods:
Animal models of peripheral neuropathy induced by various anti-cancer drugs were established, confirming the potential of HDAC6 inhibitors as a treatment for this condition. Six- to eight-week-old male Sprague Dawley rats were utilized to create these models. Mechanical allodynia and electron microscopy served as indicators of peripheral neuropathy. The HDAC6 inhibitor CKD-011 was administered at doses of 5, 10, 20, and 40 mg/kg.
Results:
In an animal model of bortezomib-induced peripheral neuropathy, CKD-011, an HDAC6 inhibitor, effectively ameliorated peripheral neuropathy. Similarly, CKD-011 administration demonstrated recovery from peripheral neuropathy in models induced with oxaliplatin, paclitaxel, and cisplatin.
Conclusions
These findings suggest that HDAC6 inhibitors have the potential to mitigate peripheral neuropathy induced by chemotherapeutic agents.
8.Higher Physical Activity is Associated with Reduced Lower Urinary Tract Symptoms in Korean Men
Seo Eun HWANG ; Jae Moon YUN ; Su Hwan CHO ; Kyungha MIN ; Ji Young KIM ; Hyuktae KWON ; Jin Ho PARK
The World Journal of Men's Health 2025;43(1):166-173
Purpose:
Identifying and managing risk factors for lower urinary tract symptoms (LUTS) is crucial because it impacts the quality of life of elderly individuals. Lifestyle factors, including physical activity (PA), and their relationship with LUTS have not been well studied. This objective of this study was to investigate the association between PA and LUTS.
Materials and Methods:
A total of 7,296 men were included in this cross-sectional study. PA was quantified in metabolic equivalent (MET)-hours per week, and LUTS severity was assessed using the international prostate symptom score. Logistic regression was used to analyze the association between PA and LUTS, including voiding and storage symptoms.
Results:
The average age of the participants was 57.8 years, and the prevalence of LUTS was 41.3%. After adjusting for potential confounders, PA was inversely associated with the prevalence and severity of moderate-to-severe LUTS, showing a dose-response pattern (all p for trend <0.01). Compared to the minimal activity group, which engaged in <5 MET-hours per week of PA, the odds ratios for moderate to severe LUTS were 0.83 (95% confidence interval [CI]: 0.72–0.97) for men engaging in 15–30 MET-hours per week, 0.82 (95% CI: 0.71–0.95) for 30–60 MET-hours per week, and 0.72 (95% CI: 0.62–0.84) for ≥60 MET-hours per week. The possible protective effect of PA was still observed in the additional analysis for voiding and storage symptoms showing the same dose-response pattern (all p for trend <0.01).
Conclusions
A higher PA level was associated with a lower prevalence and severity of total, voiding, and storage LUTS in a dose-dependent manner in Korean men.
9.Clinical Significance of Various Pathogens Identified in Patients Experiencing Acute Exacerbations of COPD: A Multi-center Study in South Korea
Hyun Woo JI ; Soojoung YU ; Yun Su SIM ; Hyewon SEO ; Jeong-Woong PARK ; Kyung Hoon MIN ; Deog Kyeom KIM ; Hyun Woo LEE ; Chin Kook RHEE ; Yong Bum PARK ; Kyeong-Cheol SHIN ; Kwang Ha YOO ; Ji Ye JUNG
Tuberculosis and Respiratory Diseases 2025;88(2):292-302
Background:
Respiratory infections play a major role in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study assessed the prevalence of bacterial and viral pathogens and their clinical impact on patients with AECOPD.
Methods:
This retrospective study included 1,186 patients diagnosed with AECOPD at 28 hospitals in South Korea between 2015 and 2018. We evaluated the identification rates of pathogens, basic patient characteristics, clinical features, and the factors associated with infections by potentially drug-resistant (PDR) pathogens using various microbiological tests.
Results:
Bacteria, viruses, and both were detected in 262 (22.1%), 265 (22.5%), and 129 (10.9%) of patients, respectively. The most common pathogens included Pseudomonas aeruginosa (17.8%), Mycoplasma pneumoniae (11.2%), Streptococcus pneumoniae (9.0%), influenza A virus (19.0%), rhinovirus (15.8%), and respiratory syncytial virus (6.4%). Notably, a history of pulmonary tuberculosis (odds ratio [OR], 1.66; p=0.046), bronchiectasis (OR, 1.99; p=0.032), and the use of a triple inhaler regimen within the past 6 months (OR, 2.04; p=0.005) were identified as significant factors associated with infection by PDR pathogens. Moreover, patients infected with PDR pathogens exhibited extended hospital stays (15.9 days vs. 12.4 days, p=0.018) and higher intensive care unit admission rates (15.9% vs. 9.5%, p=0.030).
Conclusion
This study demonstrates that a variety of pathogens are involved in episodes of AECOPD. Nevertheless, additional research is required to confirm their role in the onset and progression of AECOPD.
10.Ultrasound evaluation of clinical mimics of deep vein thrombosis: essential insights for radiologists in interpretation
Dongsuk IM ; Lyo Min KWON ; Sun Young PARK ; Min Su PARK ; Won Ju HONG
Ultrasonography 2025;44(3):171-188
Ultrasonography (US) is a sensitive and radiation-free technique for diagnosing deep vein thrombosis (DVT). Therefore, when DVT is clinically suspected but not detected on US, radiologists should consider a range of alternative differential diagnoses. This review article presents the imaging findings of clinical conditions that mimic DVT, which can be distinguished using a multimodal radiologic approach. Additionally, DVT mimics can be categorized into two groups based on whether a flat or normal waveform is observed on Doppler US. This article details the imaging findings and clinical presentations of DVT mimics, organized by these classifications. This information may help radiologists make more accurate diagnoses, enabling patients to receive appropriate treatment in a timely manner.

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