1.GSTP1-mediated inhibition of ACSL4-dependent ferroptosis via JNK pathway in DOX-induced cardiomyopathy.
Mingbo WU ; Ye ZHAO ; Dong LI ; Xueli HU ; Jiaojiao ZHOU ; Siyi CHEN ; Xin YANG ; Zegang LI ; Xiaomiao RUAN ; Jingwen YANG ; Wenwu LING
Chinese Medical Journal 2025;138(19):2498-2510
BACKGROUND:
Doxorubicin hydrochloride (DOX) is extensively used in the treatment of various tumors. However, its clinical application is limited due to dose-dependent cardiotoxicity. Currently, few effective strategies exist to mitigate or eliminate DOX-induced cardiomyopathy (DIC). Although ferroptosis is implicated in DIC and its inhibition partially alleviates the condition, the direct targets of DOX in the progression of cardiotoxicity remain unclear. This study aimed to discover the direct targets of DOX in ferroptosis-mediated DIC.
METHODS:
A DOX pulldown assay was performed to identify proteins specifically binding to DOX in murine hearts, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify candidate proteins. A cardiac injury mouse model was established by DOX treatment. Based on this, multiple ferroptosis biomarkers were detected by flow cytometry, quantitative real-time polymerase chain reaction, western blotting, immunochemistry, etc. Besides, specific activator and inhibitor of signaling pathways were applied to illuminate molecular mechanisms.
RESULTS:
Glutathione S-transferase P1 (GSTP1) was identified as a DOX target. GSTP1 activity was inhibited in DOX-treated cardiomyocytes, while its overexpression significantly alleviated DIC. Moreover, GSTP1 overexpression inhibited acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. Mechanistically, GSTP1 overexpression suppressed c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing reactive oxygen species (ROS) production and inhibiting ferroptosis in DIC.
CONCLUSIONS
This study identifies the DOX/GSTP1/JNK axis as a critical pathway mediating ACSL4-dependent ferroptosis in DIC. GSTP1 is highlighted as a potential key mediator of ferroptosis and a promising therapeutic target for DIC.
2.Effect of Qingchi Powder Retention Enema on Intestinal Flora and TLR4/NLRP3 Signaling Pathway in Peripheral Blood Mononuclear Cell of Children with Ulcerative Colitis
Xian DU ; Xueli XIN ; Shanshan ZHU
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(5):1119-1125
Objective To investigate the effect of Qingchi Powder(composed of calamina,Halloysitum Rubrum,Phellodendri Chinensis Cortex,Sophorae Flavescentis Radix,Catechu,Indigo Naturalis,Rhizoma Bletillae,and Notoginseng Radix et Rhizoma powder)retention enema on intestinal flora and Toll-like receptor 4(TLR4)/NOD-like receptor thermoprotein domain-related protein 3(NLRP3)signaling pathway in peripheral blood mononuclear cell(PBMC)of children with ulcerative colitis(UC).Methods A total of 100 children with UC were randomly divided into control group and study group,with 50 cases in each group.The control group was treated with oral administration of Mesalazin Enteric-Coated Tablets,and the study group was treated with Qingchi Powder retention enema on the basis of treatment for the control group.The treatment for the two groups lasted for 8 consecutive weeks.Before and after treatment,the distribution of intestinal flora and the relative mRNA expression levels of TLR4 and NLRP3 in PBMC,serum contents of TLR4 and NLRP3 protein,and serum levels of inflammatory factors such as tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β)and interleukin 6(IL-6)in the two groups were observed.After treatment,the clinical efficacy of the two groups was evaluated,and Spearman test was used to analyze the correlation of total effective rate with the relative mRNA expression levels of TLR4 and NLRP3 in PBMC and serum contents of TLR4 and NLRP3 protein.Results(1)After 8 weeks of treatment,the total effective rate of the study group was 94.00%(47/50),and that of the control group was 70.00%(35/50).The intergroup comparison(tested by chi-square test)showed that the efficacy of the study group was significantly superior to that of the control group(P<0.01).(2)After treatment,the number of Enterococcus and Enterobacteriaceae in the two groups was significantly lowered(P<0.05),and the number of Bifidobacterium and Lactobacillus was significantly increased compared with that before treatment(P<0.05).After treatment,the number of Enterococcus and Enterobacteriaceae in the study group was significantly lower(P<0.05)and the number of Bifidobacterium and Lactobacillus was significantly higher than that in the control group(P<0.05).(3)After treatment,the mRNA relative expression levels of TLR4 and NLRP3 in PBMC of the two groups were significantly decreased compared with those before treatment(P<0.05),and the levels in the study group were significantly lower than those in the control group(P<0.05).(4)After treatment,the serum TLR4 and NLRP3 protein levels in the two groups were significantly decreased compared with those before treatment(P<0.05),and the levels in the study group were significantly lower than those in the control group(P<0.05).(5)After treatment,the levels of serum inflammatory factors of TNF-α,IL-1β and IL-6 in the two groups significantly decreased compared with those before treatment(P<0.05),and the levels in the study group were significantly lower than those in the control group(P<0.05).(6)Spearman correlation analysis showed that the mRNA relative expression levels of TLR4 and NLRP3 in PBMC and serum TLR4 and NLRP3 protein levels in children with UC were significantly negatively correlated with the total effective rate of curative effect(P<0.001).Conclusion Qingchi Powder retention enema can down-regulate the expression levles of key signaling molecules of TLR4/NLRP3 pathway in PBMC of children with UC,regulate the intestinal flora of children,and improve the inflammatory response.It has significant curative effect and is worthy of expanding its application in clinic.
3.Research on policy framework, standards system and application of disability data
Yaru YANG ; Zhuoying QIU ; Zhongyan WANG ; Di CHEN ; Jian YANG ; Qi JING ; Na AN ; Tiantian WAN ; Xiaojia XIN ; Xiaoqin LIU ; Yuanjun DONG ; Xiangxia REN ; Ye LIU ; Yifan TIAN ; Xueli LÜ
Chinese Journal of Rehabilitation Theory and Practice 2024;30(12):1365-1375
ObjectiveTo systematically analyze international disability data policies and standards, as well as the application of disability data in policymaking, service optimization and inclusive social development, and to clarify the importance of international disability data policies, standard systems and disability data application for the development of disability-related services. MethodsThrough the analysis of policy content and research on the data standard system, this study explored the disability data policy framework, standard system and technical path of data interoperability and integration of international organizations including the United Nations (United Nations Statistics Division and United Nations Children's Fund), World Health Orgnization, United Nations Educational Scientific and Cultural Organization, and International Labour Organization. ResultsInternational organizations established disability data policy frameworks based on their respective mandates, involving data and service development, data standards, data governance, and data application. The international community established a disability data standard system for disability data collection, coding, exchange, interoperability, statistical analysis, data fusion and application. Building a standardized disability data standard system based on the framework of international health classification standards such as International Classification of Functioning, Disability and Health, and International Classification of Diseases, Eleventh Revision would ensure the consistency of cross-national disability data policies, and the interoperability and comparability of disability data, promoting the development of data-driven disability-related services, accurately identifying the service needs of people with disabilities, and optimizing service provision, thereby improving the quality of life and social participation of people with disabilities. ConclusionThe construction and implementation of international disability data policies and data standards have promoted the standardization and interoperability of disability data. With the application of big data, artificial intelligence and blockchain technologies in disability data, international cooperation and cross-industry data fusion in the field of disability data have been promoted, further promoting the development of data-driven disability services, ensuring equal opportunities for people with disabilities to enjoy service resources, and improving the coverage and quality of disability services.
4.Analysis of temporal trends of the incidence rate of tuberculosis in Shaanxi Province
Hengliang LYU ; Hongwei ZHANG ; Hui CHEN ; Xihao LIU ; Xueli ZHANG ; Xin ZHANG ; Junzhu BAI ; Shumeng YOU ; Yuanyong XU ; Wenyi ZHANG
Chinese Journal of Preventive Medicine 2024;58(11):1659-1664
Objective:To analyze the temporal trends of the incidence rate of tuberculosis (TB) in Shaanxi Province and provide a reference for WHO to control the prevalence of TB effectively.Methods:Joinpoint regression was used to analyze the trend of the incidence rate of TB in Shaanxi Province from 2004 to 2022, and the seasonal autoregressive moving average model was used to forecast the incidence rate of TB in Shaanxi Province to 2030.Results:The incidence rate of TB in Shaanxi Province decreased from 90.896/100 000 in 2004 to 35.364/100 000 in 2022, showing a general downward trend (AAPC=-7.72%, P<0.001). From 2014 to 2019, the reduction trend slowed down (APC=-0.69%, P=0.814), of which the largest decline occurred from 2019 to 2022 (APC=-13.26%, P=0.010). The predicted incidence rate of TB in Shaanxi Province from 2020 to 2022 was higher than the reported incidence rate, with the expected incidence rate of 51.342/100 000 in 2022 and 43.468/100 000 in 2030. Conclusion:The incidence rate of TB in Shaanxi Province shows a downward trend from 2004 to 2022, but the decline has shrunk in recent years. It is predicted that the downward trend will continue to slow down by 2030.
5.Analysis of temporal trends of the incidence rate of tuberculosis in Shaanxi Province
Hengliang LYU ; Hongwei ZHANG ; Hui CHEN ; Xihao LIU ; Xueli ZHANG ; Xin ZHANG ; Junzhu BAI ; Shumeng YOU ; Yuanyong XU ; Wenyi ZHANG
Chinese Journal of Preventive Medicine 2024;58(11):1659-1664
Objective:To analyze the temporal trends of the incidence rate of tuberculosis (TB) in Shaanxi Province and provide a reference for WHO to control the prevalence of TB effectively.Methods:Joinpoint regression was used to analyze the trend of the incidence rate of TB in Shaanxi Province from 2004 to 2022, and the seasonal autoregressive moving average model was used to forecast the incidence rate of TB in Shaanxi Province to 2030.Results:The incidence rate of TB in Shaanxi Province decreased from 90.896/100 000 in 2004 to 35.364/100 000 in 2022, showing a general downward trend (AAPC=-7.72%, P<0.001). From 2014 to 2019, the reduction trend slowed down (APC=-0.69%, P=0.814), of which the largest decline occurred from 2019 to 2022 (APC=-13.26%, P=0.010). The predicted incidence rate of TB in Shaanxi Province from 2020 to 2022 was higher than the reported incidence rate, with the expected incidence rate of 51.342/100 000 in 2022 and 43.468/100 000 in 2030. Conclusion:The incidence rate of TB in Shaanxi Province shows a downward trend from 2004 to 2022, but the decline has shrunk in recent years. It is predicted that the downward trend will continue to slow down by 2030.
6.Prokaryotic expression and biological activities of the hemolysin BL subunit of a pathogenic Bacillus cereus of cattle origin.
Yunjiao CHEN ; Yunjiang HE ; Qinglei MENG ; Zhilin LIU ; Xin ZHANG ; Zelin JIA ; Jiayu CUI ; Xueli WANG
Chinese Journal of Biotechnology 2023;39(12):4939-4949
Bacillus cereus belongs to Gram-positive bacteria, which is widely distributed in nature and shows certain pathogenicity. Different B. cereus strains carry different subsets of virulence factors, which directly determine the difference in their pathogenicity. It is therefore important to study the distribution of virulence factors and the biological activity of specific toxins for precise prevention and control of B. cereus infection. In this study, the hemolysin BL triayl was expressed, purified, and characterized. The results showed that the bovine pathogenic B. cereus hemolysin BL could be expressed and purified in the prokaryotic expression system, and the bovine pathogenic B. cereus hemolysin BL showed hemolysis, cytotoxicity, good immunogenicity and certain immune protection in mice. In this study, the recombinant expression of hemolysin BL triayl was achieved, and the biological activity of hemolysin BL of bovine pathogenic ceroid spore was investigated. This study may facilitate further investigating the pathogenic mechanism of B. cereus hemolysin BL and developing a detection method for bovine pathogenic B. cereus disease.
Cattle
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Animals
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Mice
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Bacterial Proteins/metabolism*
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Bacillus cereus/metabolism*
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Hemolysin Proteins/metabolism*
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Virulence Factors/metabolism*
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Enterotoxins/metabolism*
7.Application of artificial intelligence combined with multi-slice spiral CT scanning in the screening of pulmonary nodules in health examination population in government departments
Changjun PEI ; Xueli SUN ; Xin WANG ; Wei HUANG ; Mei LI ; Zhimei SHEN
Journal of Clinical Medicine in Practice 2023;27(24):89-92
Objective To explore the application value of artificial intelligence(AI)combined with multi-slice spiral CT in screening pulmonary nodules in health examination population in govern-ment departments.Methods A retrospective analysis was conducted on the chest CT screening data of health examination population in government departments who had at least diameter of one nodule ≥3 mm.All data were analyzed using AI technology combined with manual film reading.The detection rate of pulmonary nodules was recorded.Based on the risk values predicted by AI technology,the nod-ules were divided into different risk groups,and the basic characteristics of the nodules were analyzed and compared.Results The detection rate of pulmonary nodules was 60.4%.High-risk patients were more likely to present as pure ground glass nodules or mixed ground glass nodules.The average age of individuals with pulmonary nodules was higher than those without(P<0.05).There were sig-nificant differences in the basic characteristics of pulmonary nodules,including nature,morphology,internal signs,and external signs among different risk groups(P<0.05).Conclusion Multi-slice spiral CT examination of the chest scan is helpful for screening pulmonary nodules in large-scale physi-cal examination populations.The combination of AI technology and manual film reading can improve the accuracy of pulmonary nodule screening.
8.Application of artificial intelligence combined with multi-slice spiral CT scanning in the screening of pulmonary nodules in health examination population in government departments
Changjun PEI ; Xueli SUN ; Xin WANG ; Wei HUANG ; Mei LI ; Zhimei SHEN
Journal of Clinical Medicine in Practice 2023;27(24):89-92
Objective To explore the application value of artificial intelligence(AI)combined with multi-slice spiral CT in screening pulmonary nodules in health examination population in govern-ment departments.Methods A retrospective analysis was conducted on the chest CT screening data of health examination population in government departments who had at least diameter of one nodule ≥3 mm.All data were analyzed using AI technology combined with manual film reading.The detection rate of pulmonary nodules was recorded.Based on the risk values predicted by AI technology,the nod-ules were divided into different risk groups,and the basic characteristics of the nodules were analyzed and compared.Results The detection rate of pulmonary nodules was 60.4%.High-risk patients were more likely to present as pure ground glass nodules or mixed ground glass nodules.The average age of individuals with pulmonary nodules was higher than those without(P<0.05).There were sig-nificant differences in the basic characteristics of pulmonary nodules,including nature,morphology,internal signs,and external signs among different risk groups(P<0.05).Conclusion Multi-slice spiral CT examination of the chest scan is helpful for screening pulmonary nodules in large-scale physi-cal examination populations.The combination of AI technology and manual film reading can improve the accuracy of pulmonary nodule screening.
9.Effect and Mechanism of Wumeiwan Against Lewis Lung Cancer in Mice with Syndrome of Cold and Heat in Complexity Based on HGF/C-Met Signaling Pathway
Yunfeng YU ; Xueli SHANGGUAN ; Xin LI
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(21):32-41
ObjectiveTo investigate the effect and mechanism of Wumeiwan against Lewis lung cancer in mice with syndrome of cold and heat in complexity based on hepatocyte growth factor/mesenchymal-epithelial transition factor (HGF/C-Met) signaling pathway. MethodTwenty healthy male mice were classified into blank group, model group (equivalent volume of distilled water, ig), cisplatin group (4.0 mg·kg-1 cisplatin, ip), and Wumeiwan group (12.5 mL·kg-1 Wumeiwan, ig), with 5 in each group. Lewis lung cancer with the syndrome of cold and heat in complexity was induced in mice except the blank group by gavage of propylthiouracil, Zhimu Shigaotang, and Fanxieye, ice-water swimming, and subcutaneous injection of dry yeast suspension and Lewis cell suspension under the right armpit. After modeling, administration began and lasted 6 weeks. After the experiment, the tumor weight, tumor volume, tumor inhibition rate, and lung cancer metastasis-inhibiting proportion were measured and calculated. The pathological morphology of lung tissue was observed based on hematoxylin and eosin (HE) staining. The growth state of tumor tissue was analyzed by immunohistochemistry. The mRNA expression of HGF and C-Met was detected by Real-time polymerase chain reaction (PCR), and the protein expressions of HGF, C-Met, survivin, and X-linked inhibitor of apoptosis protein (XIAP) by Western blot. ResultCompared with the blank group, the model group showed high mRNA expression of HGF and C-Met and protein expression of HGF, C-Met, surviving, and XIAP (P<0.01). Compared with the model group, Wumeiwan group displayed low proportion of positive cells, positive cell density, positive score (P<0.05), histochemical score, tumor weight, tumor volume (P<0.01), mRNA expression of HGF and C-Met (P<0.01), and protein expression of HGF, C-Met, surviving, and XIAP (P<0.01). Compared with the model group, the cisplatin group displayed decrease in the proportion of positive cells, density of positive cells (P<0.05), positive score, tumor weight, tumor volume (P<0.01), mRNA expression of HGF and C-Met (P<0.01), and protein expression of HGF, C-Met, surviving, and XIAP (P<0.01), and insignificant variation in the histochemical score. Wumeiwan group had high mRNA expression of HGF (P<0.01), and insignificant variation in the proportion of positive cells, positive cell density, histochemical score, positive score, tumor weight, tumor volume, mRNA expression of C-Met, and protein expression of HGF, C-Met, surviving, and XIAP. ConclusionWumeiwan can slow down the progression of Lewis lung cancer in mice with syndrome of cold and heat I complexicity by inhibiting HGF/C-Met signaling pathway.
10.Levosimendan combined with Shengmai injection for the treatment of pump failure in 55 patients with acute myocardial infarction
Guixia LUAN ; Xueli ZHAO ; Xin ZHENG
Chinese Journal of Primary Medicine and Pharmacy 2022;29(1):23-27
Objective:To investigate the effects of levosimendan combined with Shengmai injection on pump failure in patients with acute myocardial infarction and its effects on tissue perfusion and oxygen metabolism. Methods:A total of 110 patients with acute myocardial infarction and pump failure who received treatment in Jiaozhou People's Hospital (South Branch) from July 2019 to December 2020 were included in this study. They were randomly assigned to receive either routine treatments including electrocardiography monitoring, oxygen saturation monitoring, oxygen therapy, dual antiplatelet therapy, statins, vasoactive drugs, and nitrates (control group, n = 55) or levosimendan combined with Shengmai injection based on routine treatments (observation group, n = 55) for 10 successive days. Curative efficacy, cardiac function, tissue perfusion, and oxygen metabolism capacity were compared between the control and observation groups. The 1-month mortality rate was compared between the two groups. Results:Total effective rate was significantly higher in the observation group than in the control group [58.18% (32/55) vs. 38.18% (21/55), χ2 = 4.41, P < 0.05]. After treatment, left ventricular end-diastolic diameter, left ventricular ejection fraction, and stroke volume were superior in the observation group to in the control group ( t = 2.12, –5.85, –7.33, all P < 0.05). Oxygen partial pressure, oxygenation index, central venous oxygen saturation, lactate, lactate clearance rate, and urine volume in the observation group were (103.53 ± 9.85) mmHg, (247.69 ± 18.95) mmHg, (77.56 ± 3.59)%, (3.02 ± 0.45) mmol/L, (42.89 ± 5.22)%, (40.88 ± 1.64) mL/hour, respectively, and they were (95.47 ± 11.98) mmHg, (194.69 ± 16.52) mmHg, (70.88 ± 2.13)%, (3.58 ± 0.51) mmol/L, (36.89 ± 5.14)%, and (36.55 ± 2.23) mL/hour, respectively in the observation group. There were significant differences in these indices between the control and observation groups ( t = –3.85, –15.64, –11.87, 3.11, –6.07, –11.27, all P < 0.001). At 1 month of follow-up, mortality rate was significantly lower in the observation group than in the control group [3.64% (2/55) vs. 16.36% (9/55), χ2 = 4.95, P < 0.05]. Conclusion:Levosimendan combined with Shengmai injection is a highly effective treatment for pump failure in acute myocardial infarction. It can improve cardiac function and tissue perfusion, increase oxygen metabolism capacity, and decrease mortality.

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