1.Mechanistic Study on Tougu Xiaotong Capsules in Regulating PANoptosis to Delay Degeneration of Chondrocytes in Knee Osteoarthritis
Jinxia YE ; Yixin LIN ; Xiaoqing LEI ; Yanfeng HUANG ; Changlong FU ; Desen LI ; Wenyi WANG ; Lan WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):149-161
ObjectiveTo investigate the effect of Tougu Xiaotong capsules (TGXTC) on the regulation of chondrocyte PANoptosis, delay of chondrocyte degeneration, and improvement of the symptoms in knee osteoarthritis (KOA). MethodsIn vivo experiments: 50 male C57BL/6 mice were randomly assigned into five groups (n=10 per group): sham operation group, model group, low-dose TGXTC group (7.2 g·kg-1), high-dose TGXTC group (14.4 g·kg-1), and diclofenac sodium group (0.05 g·kg-1). Except for the sham group, KOA models were established in all other groups using the modified Hulth method. Following successful model induction, the TGXTC groups received daily oral gavage of 7.2 or 14.4 g·kg-1 for 6 weeks, while the diclofenac sodium group received 0.05 g·kg-1 solution daily over the same duration. Model evaluation was performed using Lequesne MG score; micro-computed tomography (micro-CT) was used to scan the knee, hematoxylin-eosin (HE) staining and safranin O-fast green staining were used to observe the morphology of cartilage, transmission electron microscopy (TEM) was used to determine ultrastructural changes of PANoptosis. Multiple immunofluorescence (IF) co-localization assays was performed to detect the co-localization of cleaved Caspase-3, receptor-interacting protein 3 (RlPK3), and the N-terminal domain of gasdermin D (GSDMD-N) in cartilage tissue, while western blot was employed to detect the expression levels of cleaved Caspase-3, RIPK3, and GSDMD-N. In vitro experiments: The knee cartilages of 4-week-old SD rats were isolated, and a chondrocyte in vitro culture system was established through mechanical digestion with 0.2% type Ⅱ collagenase. Second-generation chondrocytes were divided into three groups: the control group, the model group (pretreated with 10 mg·L-1 lipopolysaccharide (LPS) for 24 h followed by treatment with 1 μmol·L-1 nigericin for 4 h), and the TGXTC treatment group (pretreated with 10 mg·L-1 LPS for 24 h, followed by exposure to 1 μmol·L-1 nigericin for 4 h and subsequently treated with 100 mg·L-1 TGXTC for an additional 24 h). The levels of reactive oxygen species (ROS), apoptosis, necroptosis, and pyroptosis of chondrocytes were evaluated via fluorescence microscopy following staining with ROS detection, AO/EB and YO-PRO-1/PI staining kits. Transmission electron microscopy was utilized to investigate the ultrastructural changes associated with PANoptosis in cartilage tissue of KOA mice. Inflammatory cytokine levels (IL-1β and IL-18) were measured using ELISA. Western blot was conducted to assess protein expressions related to PANoptosis, including cleaved Caspase-3, cleaved Caspase-8, RIPK3, ZBP1, GSDMD-N, and NLRP3. ResultsCompared with the sham group, the Lequesne MG scores were significantly up-regulated(P<0.01) in the model group, and the pathological changes of cartilage were significantly, with joint spaces narrower, osteophyte formation increased, secere abrasion of cartilage surface. Ultrastructural analysis revealed pronounced chondrocyte apoptosis, necroptosis, and pyroptosis, along with markedly elevated expression of cleaved Caspase-3, RlPK3, and GSDMD-N in cartilage tissue (P<0.01). In addition, The mean fluorescence intensities of ROS, orange-red fluorescence in AO/EB staining, green fluorescence and red fluorescence in YO-PRO-1/PI staining were increased of chondrocyte in the model group (P<0.01) . The levels of inflammatory factors IL-1β and IL-18 in the supernatant were increased (P<0.01). The expression of PANoptosis related proteins (cleaved Caspase-3, cleaved Caspase-8, RIPK3, ZBP1, GSDMD-N, and NLRP3) were also significantly upregulated(P<0.05). Compared to the model group, the TGXTC group demonstrated a significant improvement in various parameters of mice. These included a reduction in the Lequesne MG score, an increase in joint space, a decrease in osteophyte formation, diminished cartilage damage, reduced release of ROS, and alleviation of apoptotic, necroptotic, and pyroptotic processes in chondrocytes. Additionally, mitochondrial swelling and endoplasmic reticulum dilation were also mitigated. The levels of ROS as well as IL-1β and IL-18 were significantly decreased (P<0.05). Furthermore, the expression levels of proteins associated with PANoptosis in cartilage tissue showed marked reductions (P<0.05). Similar results were observed in chondrocytes: cleaved Caspase-3, cleaved Caspase-8, RIPK3, ZBP1, GSDMD-N, and NLRP3 exhibited significant decreases as well (P<0.05). ConclusionTGXTC may mitigate chondrocytes degeneration and alleviate KOA symptoms by reducing oxidative stress and suppressing the activation of PANoptosis pathways.
2.Mechanistic Study on Tougu Xiaotong Capsules in Regulating PANoptosis to Delay Degeneration of Chondrocytes in Knee Osteoarthritis
Jinxia YE ; Yixin LIN ; Xiaoqing LEI ; Yanfeng HUANG ; Changlong FU ; Desen LI ; Wenyi WANG ; Lan WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):149-161
ObjectiveTo investigate the effect of Tougu Xiaotong capsules (TGXTC) on the regulation of chondrocyte PANoptosis, delay of chondrocyte degeneration, and improvement of the symptoms in knee osteoarthritis (KOA). MethodsIn vivo experiments: 50 male C57BL/6 mice were randomly assigned into five groups (n=10 per group): sham operation group, model group, low-dose TGXTC group (7.2 g·kg-1), high-dose TGXTC group (14.4 g·kg-1), and diclofenac sodium group (0.05 g·kg-1). Except for the sham group, KOA models were established in all other groups using the modified Hulth method. Following successful model induction, the TGXTC groups received daily oral gavage of 7.2 or 14.4 g·kg-1 for 6 weeks, while the diclofenac sodium group received 0.05 g·kg-1 solution daily over the same duration. Model evaluation was performed using Lequesne MG score; micro-computed tomography (micro-CT) was used to scan the knee, hematoxylin-eosin (HE) staining and safranin O-fast green staining were used to observe the morphology of cartilage, transmission electron microscopy (TEM) was used to determine ultrastructural changes of PANoptosis. Multiple immunofluorescence (IF) co-localization assays was performed to detect the co-localization of cleaved Caspase-3, receptor-interacting protein 3 (RlPK3), and the N-terminal domain of gasdermin D (GSDMD-N) in cartilage tissue, while western blot was employed to detect the expression levels of cleaved Caspase-3, RIPK3, and GSDMD-N. In vitro experiments: The knee cartilages of 4-week-old SD rats were isolated, and a chondrocyte in vitro culture system was established through mechanical digestion with 0.2% type Ⅱ collagenase. Second-generation chondrocytes were divided into three groups: the control group, the model group (pretreated with 10 mg·L-1 lipopolysaccharide (LPS) for 24 h followed by treatment with 1 μmol·L-1 nigericin for 4 h), and the TGXTC treatment group (pretreated with 10 mg·L-1 LPS for 24 h, followed by exposure to 1 μmol·L-1 nigericin for 4 h and subsequently treated with 100 mg·L-1 TGXTC for an additional 24 h). The levels of reactive oxygen species (ROS), apoptosis, necroptosis, and pyroptosis of chondrocytes were evaluated via fluorescence microscopy following staining with ROS detection, AO/EB and YO-PRO-1/PI staining kits. Transmission electron microscopy was utilized to investigate the ultrastructural changes associated with PANoptosis in cartilage tissue of KOA mice. Inflammatory cytokine levels (IL-1β and IL-18) were measured using ELISA. Western blot was conducted to assess protein expressions related to PANoptosis, including cleaved Caspase-3, cleaved Caspase-8, RIPK3, ZBP1, GSDMD-N, and NLRP3. ResultsCompared with the sham group, the Lequesne MG scores were significantly up-regulated(P<0.01) in the model group, and the pathological changes of cartilage were significantly, with joint spaces narrower, osteophyte formation increased, secere abrasion of cartilage surface. Ultrastructural analysis revealed pronounced chondrocyte apoptosis, necroptosis, and pyroptosis, along with markedly elevated expression of cleaved Caspase-3, RlPK3, and GSDMD-N in cartilage tissue (P<0.01). In addition, The mean fluorescence intensities of ROS, orange-red fluorescence in AO/EB staining, green fluorescence and red fluorescence in YO-PRO-1/PI staining were increased of chondrocyte in the model group (P<0.01) . The levels of inflammatory factors IL-1β and IL-18 in the supernatant were increased (P<0.01). The expression of PANoptosis related proteins (cleaved Caspase-3, cleaved Caspase-8, RIPK3, ZBP1, GSDMD-N, and NLRP3) were also significantly upregulated(P<0.05). Compared to the model group, the TGXTC group demonstrated a significant improvement in various parameters of mice. These included a reduction in the Lequesne MG score, an increase in joint space, a decrease in osteophyte formation, diminished cartilage damage, reduced release of ROS, and alleviation of apoptotic, necroptotic, and pyroptotic processes in chondrocytes. Additionally, mitochondrial swelling and endoplasmic reticulum dilation were also mitigated. The levels of ROS as well as IL-1β and IL-18 were significantly decreased (P<0.05). Furthermore, the expression levels of proteins associated with PANoptosis in cartilage tissue showed marked reductions (P<0.05). Similar results were observed in chondrocytes: cleaved Caspase-3, cleaved Caspase-8, RIPK3, ZBP1, GSDMD-N, and NLRP3 exhibited significant decreases as well (P<0.05). ConclusionTGXTC may mitigate chondrocytes degeneration and alleviate KOA symptoms by reducing oxidative stress and suppressing the activation of PANoptosis pathways.
3.Current Status,Challenges,and Strategies of Basic Research on the Brain-Gut Interaction Theory for Spleen and Stomach Diseases in Traditional Chinese Medicine
Ting CHEN ; Jinxia ZHU ; Xiaohua HOU ; Xiaoli ZHANG ; Lifei ZHENG ; Lei ZHANG ; Xinxin WANG ; Xuan LI ; Xudong TANG
Journal of Traditional Chinese Medicine 2026;67(5):517-522
The brain-gut interaction theory is a multidimensional integrative concept based on the brain-gut axis, involving neural, endocrine, and immune regulatory networks as well as the gut microbiota. Zang-fu organs (脏腑) theory in traditional Chinese medicine (TCM) shows a high degree of consistency with the brain-gut interaction theory, and the core functions such as the spleen and stomach governing the ascending of the clear and descending of the turbid, the liver governing the free flow of qi, and the heart governing mental and emotional activities are closely associated with the multi-level regulatory mechanisms of the brain-gut axis. TCM therapy can modulate brain-gut interactions through multiple pathways in the treatment of spleen and stomach diseases, including the regulation of gastrointestinal hormone secretion, neurotransmitter levels, the hypothalamic-pituitary-adrenal (HPA) axis, immune homeostasis and inflammatory responses, as well as the gut microecology. However, current basic research on the brain-gut interaction theory in TCM for spleen and stomach diseases still faces several challenges, such as difficulties in integrating TCM spleen-stomach theory with modern pathophysiology, lack of innovation in research concepts, and limitations in research methodologies. It is therefore proposed that multidisciplinary collaboration, multi-omics technologies, and targeted research approaches should be adopted to provide more comprehensive methods for basic research on TCM spleen and stomach diseases, thereby promoting the in-depth development of brain-gut interaction theory.
4.Evidence-based progress and clinical enlightenment of low-dose colchicine in secondary prevention of atherosclerotic cardiovascular disease
Xianghong WANG ; Jinxia ZHANG ; Rui LI ; Ge GUAN ; Xue GONG ; Mengmiao ZHANG ; Bo JI ; Jian LI ; Zhihui JIANG
China Pharmacy 2026;37(19):2608-2614
Residual inflammatory risk (RIR) is a key issue to be urgently addressed in the secondary prevention of atherosclerotic cardiovascular disease (ASCVD). Targeted intervention of RIR has become a novel target for drug development and clinical management. A series of high-quality randomized controlled trials (RCTs), including COLCOT, LoDoCo2 and CLEAR SYNERGY, provided high-level evidence and confirmed that low-dose colchicine (0.5 mg/d) significantly reduced the risk of cardiovascular events in ASCVD patients at stable stage or after the acute phase, while its efficacy varied in different clinical scenarios. International authoritative guidelines from the European Society of Cardiology and the American Heart Association/American College of Cardiology include low-dose colchicine in the recommendations for ASCVD secondary prevention. Two domestic guidelines released in 2024, namely the Guideline for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndrome ( 2024 ) and the Guideline for the Diagnosis and Management of Chronic Coronary Syndrome in China , have also added relevant recommendations. Nevertheless, due to potential racial differences, safety concerns regarding drug-drug interactions, and the relative lack of clinical evidence in China, especially the absence of prospective RCTs using low-dose colchicine for secondary prevention of ASCVD patients, current clinical recommendations still mainly based on international evidence and guidelines, and should not be simply extrapolated.
5.Visualization analysis of macrophage polarization in tissue repair process
Jinxia CHANG ; Yufei LIU ; Shaohui NIU ; Chang WANG ; Jianchun CAO
Chinese Journal of Tissue Engineering Research 2025;29(7):1486-1496
BACKGROUND:During tissue repair and regeneration,macrophages exhibit multiple activities such as promoting inflammation,anti-inflammation,fibrosis,and wound healing at various stages of tissue damage.The heterogeneity and balanced polarization of macrophages are decisive in organ repair. OBJECTIVE:To explore the research hotspots and development trends in the field of macrophage polarization in tissue repair through visualization analysis methods,as well as the research level of global scientific and clinical workers in this field. METHODS:Using bibliometric analysis methods,this study employed Citespace literature visualization analysis software and VOSviewer tools,retrieving related literature from 2013 to 2023 in the Web of Science Core Collection's Science Citation Index Expanded(SCI-Expanded)and Social Sciences Citation Index Expanded(SSCI-Expanded)databases.The analysis results were presented in a dynamic map format,revealing the main trends and focuses of the research. RESULTS AND CONCLUSION:The number of publications in this field had dramatically increased from 2013 to 2023,with a significant rise starting in 2017.Chinese researchers had the highest number of publications,with 642 papers,while American researchers began focusing on this field early on.Professor Elisseeff Hennifer H had made a substantial contribution to the research in this area.Shanghai Jiao Tong University had produced the most publications.In recent years,keywords such as"hyaluronic acid"and"regulation"had been prevalent.Macrophage polarization research in tissue repair primarily concentrates on its multifunctional regulatory mechanisms,interactions with other cell types,and its behavior under specific pathological conditions.The main research areas include the role of macrophages in wound healing,cardiovascular diseases,chronic inflammation,tumor microenvironments,and regenerative medicine.A deeper understanding of the multifunctionality and polarization mechanisms of macrophages can lead to the development of new therapeutic strategies to enhance tissue repair and regeneration,thereby improving patient treatment outcomes.
6.Acute impact of persistent high ambient fine particulate matter exposures on hospital visits for respiratory diseases from 2013 to 2018 in the Beijing-Tianjin-Hebei region and surrounding areas
Yiqi QIU ; Chen CHEN ; Jianan LI ; Yue LIANG ; Changzhen XIANG ; Huiting LING ; Jinxia YANG ; Yu WANG ; Jianlong FANG ; Jiaonan WANG ; Chen MAO ; Xiaoming SHI
Chinese Journal of Epidemiology 2025;46(6):979-985
Objective:To investigate the acute effects of persistent high exposure to atmospheric fine particulate matter (PM 2.5) on residents' outpatient visits for respiratory diseases. Methods:We collected daily outpatient records from 92 hospitals in 13 cities across the Beijing-Tianjin-Hebei region, along with daily PM 2.5, nitrogen dioxide (NO 2), and meteorological data from 2013 to 2018. Five persistent high PM 2.5 exposure scenarios were defined in terms of daily mean PM 2.5 concentrations (>75 μg/m 3 and >150 μg/m 3), duration (≥2 days and ≥3 days), and whether or not there was concurrent exposure to high levels of NO 2 (daily mean NO 2 concentration >50 μg/m 3). A two-stage statistical analysis strategy based on a generalized linear model was applied to conduct a time-series analysis to assess the exposure-response relationship between persistent high PM 2.5 exposure scenarios and residents' outpatient visits for a variety of respiratory diseases, and to estimate excess outpatient visits. Results:During the period, M ( Q1, Q3) PM 2.5 and NO 2 concentrations were 61.2 (42.3, 95.1) μg/m 3 and 40.2 (31.4, 54.4) μg/m 3, respectively, and the daily respiratory disease outpatient visits were 57 (52, 66) cases. When compared with non-permanent high PM 2.5 exposure periods, exposure scenarios with PM 2.5 >75 μg/m 3 and lasting for ≥2 days caused an increased risk of outpatient visits for respiratory diseases by 2.10% (95% CI: 1.44%-2.77%), and resulted in 43 787 (95% CI: 30 025-57 757) excess visits; in this scenario, the concurrent exposure to high levels of NO 2 had a greater acute effect on respiratory disease visits than the absence of exposure to high levels of NO 2 ( P<0.001). The risk of respiratory disease visits increased substantially by 4.41% (95% CI: 3.15%-5.68%) when the daily mean PM 2.5 concentration exceeded 150 μg/m 3 for ≥2 days. Subgroup disease analyses showed that scenarios with daily mean PM 2.5 concentrations exceeding 75 μg/m 3 for ≥3 days caused a significant increase in the risk of lower respiratory tract infections, chronic lower respiratory disease, and asthma visits. Conclusions:Sustained persistent high PM 2.5 exposure increases the risk of outpatient visits for various respiratory diseases; concurrent exposure to high concentrations of NO 2 leads to a greater risk of visiting the clinic, suggesting that the prevention and control of PM 2.5 pollution should be synchronized with the control of mobile source emissions, to synergistically manage the compound pollution of PM 2.5 and NO 2 in the atmosphere.
7.Clinical case analysis: fever thrombus space-occupying lesion in right ventricle
Hui WEI ; Jinxia ZHAO ; Zhonqiang YAO ; Song WU ; Meng WANG ; Xiang ZHU ; Rong MU
Chinese Journal of Rheumatology 2025;29(11):946-950
Objective:To improve the awareness of Beh?et′s disease with ventricular neoplasm.Methods:A case with fever, thrombosis, and right ventricular neoplasm was described. The diagnosis and treatment were analyzed and discussed.Results:A young male with genital ulcers and oral ulcers, ocular, skin, and vascular lesions presenting as large venous thrombus, was diagnosed with Beh?et′s disease. Pathological results of space-occupying lesion in right ventricle revealed inflammation and necrotic substance. Endocarditis was considered. Glucocorticoids and cyclophosphamide was given, together with warfarin. During one-year follow-up, the patient remained stable.Conclusion:It is difficult to distinguish between Beh?et′s disease with cardiac neoplasm and infective endocarditis or cardiac tumor based on clinical manifestations and imaging only. Multidisciplinary management is a valuable approach for the diagnosis and treatment.
8.Analysis on influence of dynamic cycle management mode on management for medical equipment
Manfei XUE ; Qianqian WANG ; Yan WANG ; Jinxia HUANG
China Medical Equipment 2025;22(9):94-97
Objective:To construct dynamic cycle management mode of medical equipment,so as to analyze the influence of that on management effect of medical equipment in the department of neurosurgery,and improve the management effect of neurosurgery equipment.Method:Based on the full-process monitoring,full participation and all-round management of the dynamic cycle management mode,the full life cycle management was implemented on medical instruments and equipment.A total of 1,269 used medical equipment in the department of neurosurgery of the Second Affiliated Hospital of Air Force Medical University from January 2022 to December 2023 were selected.During the period from January 2022 to December 2022,the conventional management mode was adopted to manage these equipment.From January and December 2023,the dynamic cycle management mode was adopted to manage them.The management effects of equipment failure and the incidence of risk events of the two management modes were compared.A self-made satisfaction questionnaire was used to investigate the satisfaction scores of medical staffs,who used the equipment,for maintaining and using the equipment.Results:The time of average internal reporting for repair,the time of external reporting for repair,the time of diagnosing fault,total time of reporting repair and total maintenance time in dynamic cycle management mode were respectively(3.15±1.04)min,(19.34±2.81)min,(22.66±3.73)min,(10.04±1.11)min and(5.38±1.92)d,which were significantly lower than those in conventional management mode(t=15.878,21.553,18.755,20.486,7.636,P<0.05).The incidence of risk events of equipment in dynamic cycle management mode was significantly lower than that in conventional management group(x2=8.635,P<0.05).The satisfaction scores of medical staffs who used equipment in dynamic cycle management mode were significantly higher than those in conventional management mode in the timeliness of reporting repair,the speed of diagnosis and maintenance,the used effect after maintenance for failure of equipment,and the differences were significant(t=7.364,7.381,5.413,P<0.05).Conclusion:The application of dynamic cycle management mode for medical equipment in the management for instrument and equipment of the department of neurosurgery in hospital can improve management effect for equipment,and reduce incidence of risk events of equipment,and enhance the satisfaction of staffs who use equipment.
9.Mechanism of spasmolytic polypeptide-expressing metaplasia in gastric mucosa induced by Helicobacter pylori infection
Hainuo WANG ; Yufan LI ; Yuying WANG ; Qianying SHEN ; Jinxia ZHU ; Lifei ZHENG
Basic & Clinical Medicine 2025;45(1):130-134
Helicobacter pylori(H.pylori)infection triggers gastric mucosal inflammatory responses and spasmolytic polypeptide-expressing metaplasia(SPEM).These pathological conditions can escalate the severity of chronic gas-tritis,gastric ulcers and even cause gastric cancer.SPEM is frequently viewed as an early sign of gastric mucosal injury and the onset of carcinogenesis.A comprehensive analysis of the genesis and molecular regulation of SPEM cells in the context of H.pylori infection further has enlightened the pathogenesis of gastric mucosal diseases and provide new ideas and targets for diagnosing and treatment of H.pylori-related gastric mucosal diseases.This paper reviews a variety of molecular biomarkers associated with SPEM,encompassing TFF2,CD44v9,and AQP5,and delineates their pivotal regulatory functions in H.pylori infection and SPEM.This paper also reviews the origination of SPEM cells and pertinent molecular regulatory mechanisms.
10.Treatment and prognosis analysis of endometrial cancer with positive sentinel lymph node biopsy
Hao WANG ; Liangzi JIANG ; Jinxia ZHOU ; Li YAN
Cancer Research and Clinic 2025;37(5):357-361
Objective:To explore the clinical significance of complementary systematic lymphadenectomy (SLND) for advanced endometrial cancer (EC) with positive sentinel lymph node biopsy (SLNB) results and the risk factors influencing the prognosis of this group of individuals.Methods:A retrospective case-controlled study was conducted. The clinical data of EC patients diagnosed by histopathologic examination between January 2000 and December 2018 in National Cancer Institute the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively analyzed. SLNB-positive EC patients were screened and were classified into the SLNB group and the SLNB+SLND group according to the lymph node surgical approach. χ2 test was used for the comparison of clinicopathological characteristics between the 2 groups, the Kaplan-Meier method was used for plotting the survival curves, and the Cox proportional hazards model was used for univariate and multivariate analyses on the factors influencing patients' overall survival (OS). Results:A total of 222 patients were included, including 86 cases in the SLNB group and 136 cases in the SLNB+SLND group, and there were no statistically significant differences in the comparison of clinicopathologic characteristics between the 2 groups (all P > 0.05). The 1-, 3-year OS rates were 94.0%, 80.5%, respectively in the SLNB group; the 1-, 3-year OS rates were 91.8%, 75.7%, respectively in the SLNB+SLND group, and the difference in the OS was not statistically significant ( χ2 = 0.05, P = 0.818). Multivariate Cox regression analysis showed that age ≥ 71 years ( HR = 2.35, 95% CI: 1.27-4.35, P = 0.007), histologic grade Ⅲ ( HR = 3.80, 95% CI: 1.22-11.83, P = 0.021), and not receiving radiotherapy ( HR = 2.08, 95% CI: 1.17-3.70, P = 0.013) were independent risk factors for OS in SLNB-positive EC patients. Conclusions:Age, histologic grade and radiotherapy are independent influencing factors of OS in advanced EC patients with positive SLNB. The further SLND does not provide an additional survival benefit for patients.

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