1.Chidamide triggers pyroptosis in T-cell lymphoblastic lymphoma/leukemia via the FOXO1/GSDME axis.
Xinlei LI ; Bangdong LIU ; Dezhi HUANG ; Naya MA ; Jing XIA ; Xianlan ZHAO ; Yishuo DUAN ; Fu LI ; Shijia LIN ; Shuhan TANG ; Qiong LI ; Jun RAO ; Xi ZHANG
Chinese Medical Journal 2025;138(10):1213-1224
BACKGROUND:
T-cell lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is an aggressive form of hematological malignancy associated with poor prognosis in adult patients. Histone deacetylases (HDACs) are aberrantly expressed in T-LBL/ALL and are considered potential therapeutic targets. Here, we investigated the antitumor effect of a novel HDAC inhibitor, chidamide, on T-LBL/ALL.
METHODS:
HDAC1, HDAC2 and HDAC3 levels in T-LBL/ALL cell lines and patient samples were compared with those in normal controls. Flow cytometry, transmission electron microscopy, and lactate dehydrogenase release assays were conducted in Jurkat and MOLT-4 cells to assess apoptosis and pyroptosis. A specific forkhead box O1 (FOXO1) inhibitor was used to rescue pyroptosis and upregulated gasdermin E (GSDME) expression caused by chidamide treatment. The role of the FOXO1 transcription factor was evaluated by dual-luciferase reporter and chromatin immunoprecipitation assays. The efficacy of chidamide in vivo was evaluated in a xenograft mouse.
RESULTS:
The expression of HDAC1, HDAC2 and HDAC3 was significantly upregulated in T-LBL/ALL. Cell viability was obviously inhibited after chidamide treatment. Pyroptosis, characterized by cell swelling, pore formation on the plasma membrane and lactate dehydrogenase leakage, was identified as a new mechanism of chidamide treatment. Chidamide triggered pyroptosis through caspase 3 activation and GSDME transcriptional upregulation. Chromatin immunoprecipitation assays confirmed that chidamide led to the increased transcription of GSDME through a more relaxed chromatin structure at the promoter and the upregulation of FOXO1 expression. Moreover, we identified the therapeutic effect of chidamide in vivo .
CONCLUSIONS
This study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.
Humans
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Pyroptosis/drug effects*
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Forkhead Box Protein O1/genetics*
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Aminopyridines/pharmacology*
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Animals
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Mice
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Benzamides/pharmacology*
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Cell Line, Tumor
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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*
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Phosphate-Binding Proteins/metabolism*
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Histone Deacetylase Inhibitors/pharmacology*
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Jurkat Cells
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Histone Deacetylases/metabolism*
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Apoptosis/drug effects*
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Gasdermins
2.Root rot and control of Panax quinquefolium: a review.
Rao-Jing LI ; Jia-le LIU ; Jian ZHANG ; Juan CHEN
China Journal of Chinese Materia Medica 2025;50(9):2317-2323
Panax quinquefolium, also known as American ginseng, is a perennial herb in the Araliaceae family. It has the effects of replenishing Qi and nourishing Yin, clearing heat and generating saliva. Additionally, it has protective effects on the nerves, improves myocardial ischemia and hypoxia, regulates metabolism, enhances the body's immunity, and is known as "green gold". However, with the development of the industry and the expansion of planting scales, P. quinquefolium faces serious disease issues that are difficult to prevent and control. Among these, root rot, often referred to as "plant cancer", is one of the most destructive plant diseases affecting the yield and quality of P. quinquefolium. P. quinquefolium root rot is caused by the fungi Fusarium(genus) and Ilyonectria(genus), which severely affect the root system and limit the production and quality of P. quinquefolium, thus restricting the development of the P. quinquefolium industry. In recent years, research on P. quinquefolium root rot has attracted significant attention and made some progress. However, the mechanisms of interaction between the root rot pathogens and the host plant remain unclear. This paper reviews the research progress on the pathogens, infection cycle, disease prevalence, pathogenesis, and biological control of P. quinquefolium root rot to provide prospects for future research, aiming to provide references for the in-depth study and effective control of root rot, and to promote the green and healthy development of the P. quinquefolium industry.
Panax/microbiology*
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Plant Diseases/prevention & control*
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Plant Roots/microbiology*
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Fusarium/pathogenicity*
4.Correlation of serum metabolites and clinical features in patients with peripheral T-cell lymphoma
Yishuo DUAN ; Jun RAO ; Jing XIA ; Naya MA ; Shijia LIN ; Fu LI ; Shuhan TANG ; Sha ZHOU ; Yunjing ZENG ; Xinlei LI ; Dezhi HUANG ; Qiong LI ; Bangdong LIU ; Xianlan ZHAO ; Jin WEI ; Xi ZHANG
Journal of Army Medical University 2024;46(4):352-358
Objective To explore the changes in serum energy metabolites in patients with peripheral T-cell lymphoma,and investigate serum biomarkers for monitoring peripheral T-cell lymphoma from the perspective of energy metabolism.Methods Multiple/selected reaction monitoring(MRM/SRM)was used to detect the energy-related metabolites in the sera of 16 patients with newly diagnosed peripheral T-cell lymphoma admitted in the Hematology Medical Center of the Second Affiliated Hospital of Army Medical University from November 2020 to December 2021,as well as 10 recruited healthy volunteers.The corresponding clinical data including medical history,laboratory results and image data were collected and retrospectively analyzed.Results Significant differences were seen in the contents and expression profiles of serum energy metabolism-related products between the patients and the healthy volunteers.The patients had significantly reduced serum contents of cyclic AMP,succinate,citrate and cis-aconitate(P<0.05),and elevated D-glucose 6-phosphate content(P<0.05).The serum contents of citrate and succinate were negatively correlated with the risk stratification(low-,moderate-and high-risk)and clinical stage of the disease(P<0.05).Meanwhile,there was a negative correlation between the contents of L-malic acid and citrate and the mid-term efficacy evaluation results,such as complete/partial response(CR/PR)or stable disease(SD)(P<0.05).For patients with extranodal NK/T cell lymphoma(n=10),there were also significant reductions in the contents of cyclic AMP,succinate,citrate,isocitrate and cis-aconitate in the sera of patients compared with healthy volunteers(P<0.05),and the contents of citrate and succinate were negatively correlated with the clinical stage(P<0.05)and were rather correlated with mid-term efficacy evaluation results(CR/PR or SD)(P<0.05).For patients with angioimmunoblastic T-cell lymphoma(n=6),the serum contents of cyclic AMP,citrate and succinate were significantly lower,while the content of D-glucose 6-phosphate was higher when compared with the healthy volunteers(P<0.05),and the content of succinate was negatively correlated with both clinical stage and risk grade of the patients(P<0.05).Conclusion There are 5 serum differential metabolites identified between patients with peripheral T-cell lymphoma and healthy controls,and succinate and citrate are expected to be serum biomarkers of peripheral T-cell lymphoma.
5.Expert consensus on the bi-directional screening for Mycobacterium tuberculosis and human immunodeficiency virus
Xin SHEN ; Yinzhong SHEN ; Eryong LIU ; Dingyong SUN ; Dongmin LI ; Yun HE ; Jinge HE ; Lin XU ; Bin CHEN ; Chengliang CHAI ; Lianguo RUAN ; Yong GAO ; Aihua DENG ; Zhen NING ; Jing CHEN ; Xiaofeng LIU ; Kaikan GU ; Lixin RAO
Shanghai Journal of Preventive Medicine 2024;36(4):327-336
Tuberculosis (TB) and human immunodeficiency virus infection / acquired immune deficiency syndrome (HIV/AIDS) are both serious global public health threats. Early detection of infected persons and/or patients through TB/HIV bi-directional screening is crucial for prevention and control strategy in China and globally. In recent years, with the promotion and application of new TB and HIV detection technologies worldwide, TB/HIV bi-directional screening technologies and strategies have made remarkable changes. This expert consensus introduces the significance and challenges of TB/HIV bi-directional screening, summarizes important progress of research and applications, and makes recommendations on screening measures and procedures to further strengthen TB/HIV bi-directional screening in China.
6.Study on the protective effect of soybean phospholipid powder on nerve injury
Mengli ZHOU ; Xianyue RAO ; Jing FANG ; Hao WANG
Acta Universitatis Medicinalis Anhui 2024;59(5):797-802
Objective To investigate the protective effects and mechanisms of soybean phospholipid powder on nerve cells in vitro and rats neural tissues.Methods In the cell experiments, the cytotoxicity of soybean phospho-lipid powder with different concentrations on mouse microglia cells (BV2) and rat adrenal pheochromocytoma (PC12) cells was observed by cell counting kit-8(CCK-8) assay.The effect of soybean phospholipid powder on the NO level of BV2 cells was analyzed by NO determination experiment, and the synaptic growth of PC12 cells was observed under the microscope.In the animal experiment, the cognitive dysfunction of rat was simulated by scopol-amine rat model.Then the learning and memory abilities of rat were tested by Morris water maze experiment;hipp-ocampal tissue morphology and nerve cell density of scopolamine model mice were observed by hematoxylin-eosin staining (HE) staining.Results Soybean phospholipid powder had no obvious cytotoxicity on BV2 cells and PC12 cells within the concentration of 1000μg/ml.Compared with the control group, the NO secretion of BV2 cells pre-treated with soybean phospholipid powder significantly decreased (P<0.01) , and the neuronal synapse growth of PC12 cells significantly increased (P <0.01) .In comparison to the model group, soybean phospholipid powder significantly improved the learning and memory ability of scopolamine model rats (P<0.05) , reduced the neuronal damage in dentate gyrus (DG), cornu ammonis3 (CA3), cornu ammonis1 (CA1) areas of hippocampus, and in-creased the density of nerve cells (P<0.001).Conclusion Soybean phospholipid powder can play a neuropro-tective role by reducing neuroinflammation and promoting neuronal synapse growth at the cellular level, and im-prove the learning and memory ability of rats with cognitive impairment, reduce hippocampal tissue damage.
7.Study on the mechanism of electroacupuncture stimulation to activate the acupoint effect and promote skeletal muscle repair
Yuting HUANG ; Jun LIAO ; Tianyu RAO ; Kezhi LIU ; Jia LIN ; Yuye LIN ; Chufan ZENG ; Guojun ZHANG ; Xia ZHANG ; Xiubing TONG ; Jingyu ZHANG ; Yu KAN ; Yanping FANG ; Xianghong JING ; Xuan WANG
Journal of Beijing University of Traditional Chinese Medicine 2024;47(8):1160-1170
Objective To investigate the mechanism of inducing macrophage polarization induced by acupoint effect of electroacupuncture to promote the repair of acute skeletal muscle injury.Methods 45 SD rats were randomly divided into blank group,model group,electroacupuncture group(EA group),sodium chrominate group (DSCG group) and electroacupuncture+sodium chrominate group (hereinafter referred to as EA+DSCG group),with 9 rats in each group. The rats in the EA group and the EA+DSCG group were subjected to EA intervention at the right "Chengshan" (BL57) and "Yanglingquan"(GB34),with a frequency of 2 Hz/100 Hz. The gait changes of rats were recorded by animal gait analyzer. The morphological changes of the right gastrocnemius were observed by HE staining. The changes of mast cell aggregation and degranulation in local skin muscles of "chengshan" point were observed by toluidine blue staining. The expressions of Pax7,MyoD and skin mast cells and 5-HT in the right gastrocnemius were detected by immunofluorescence method. The positive expressions of CD68 and CD206 in right gastrocnemius macrophage was observed by immunohistochemical staining.Results Compared with blank group,the wiggle time of the right hind leg in model group and DSCG group increased,stride length decreased,HE staining showed inflammatory cell infiltration,myocyte enlargement,degeneration and necrosis. The degranulation rate of local skin mast cells in "Chengshan" (BL57) area increased,and the expressions of mast cell tryptase,5-HT,Pax7,MyoD,CD68 and CD206 increased (P<0.05). Compared with model group,the wiggle time of the right hind leg in EA group and EA+DSCG group decreased,stride length increased,HE staining showed that inflammatory cell infiltration was reduced,muscle cells were uniform in size and arranged neatly. Mast cell degranulation rate increased significantly in EA group,and the expressions of mast cell tryptase,5-HT,Pax7,MyoD and CD206 increased (P<0.05),while CD68 expression decreased (P<0.05). Compared with EA+DSCG group,the degranulation rate of mast cells and the expressions of mast cell tryptase,5-HT,Pax7,MyoD and CD206 increased (P<0.05),while CD68 expression decreased in EA group (P<0.05). Conclusion EA "Chengshan" (BL57) and "Yanglingquan" (GB34) can stimulate acupuncture points to locally induce mast cell degranulation,promote the polarization of macrophages,and then activate muscle satellite cells to play the regulatory process of repairing skeletal muscle injury.
8.Application of GLIM criteria for malnutrition diagnosis in 5 236 elderly inpatients
Jingsi SONG ; Chunyan DU ; Shi QIU ; Junchi YE ; Na YU ; Zhiyong RAO ; Xiaofan JING
Chinese Journal of Clinical Nutrition 2024;32(3):150-155
Objective:To analyze the nutritional status of elderly inpatients using Global Leadership Initiative on Malnutrition (GLIM) criteria.Methods:A total of 5 236 elderly patients (aged 65 years or older) who were hospitalized at the West China Hospital, Sichuan University from March 2021 to March 2022 were included. The nutritional status was analyzed using the GLIM diagnostic criteria for malnutrition.Results:The rate of patients at nutritional risk was 30.29%, and the incidence of malnutrition as per GLIM criteria was 15.64%. The levels of hemoglobin, albumin, triglycerides, and cholesterol, and body mass index of the malnutrition group were lower compared with the non-malnutrition group, and the differences were statistically significant ( P<0.05). The non-malnutrition group had significantly shorter hospital stay and lower hospitalization costs compared with the malnutrition group ( P<0.001). Conclusions:The GLIM criteria is suitable for evaluating the nutritional status in elderly inpatients. The incidence of malnutrition in elderly inpatients is relatively high, which deserves attention in clinical management.
9.Visualization analysis of the current status and trend of researches related to cerebral hemorrhage surgery based on CiteSpace and VOSviewer
Junhong ZENG ; Taotao SHEN ; Guofeng WU ; Jing OUYANG ; Jiaqin RAO ; Shasha LUO ; Yizhi ZHANG ; Cui XIONG ; Ying GU
Chinese Journal of Cerebrovascular Diseases 2024;21(7):455-466
Objective To summarize and explore the current state,hotspots,and trends in the field of surgical treatment for intracerebral hemorrhage(ICH)over the past decade through a bibliometric and visualization analysis of relevant literature.Methods Relevant Chinese and English literature on the surgical treatment of ICH,published from January 1,2014 to April 1,2024,was retrieved and screened from CNKI and Web of Science databases.Visualization analysis was conducted using CiteSpace,VOSviewer,and other software to analyze the number of published papers,authors,countries,institutions,etc.Social network analysis diagrams of authors,keyword clustering network analysis diagrams,keyword burst strength,and keyword timeline maps were also utilized.Results(1)A total of 3 456 relevant papers were included,with 2 173 in Chinese and 1 283 in English.From 2014 to 2021,the annual number of Chinese publications on ICH surgery was higher than that of English publications,but the number of Chinese publications began to decline from 2016.The number of English publications showed an overall increasing trend.(2)A total of 6 367 authors were identified from the English literature,with notable collaboration networks led by researchers such as Mocco J,Hanley DF,Ziai WC,You C,and Tang ZP.The Chinese literature included 6 522authors,with prominent collaboration networks led by Wang LK,Cai Q,Ku HB,Zhang S,and Zhu SQ.(3)Analysis of the countries involved in the English literature showed that 31 countries participated in research on ICH surgery,with China leading in the number of publications(505),followed by the United States(330)and Germany(106).The top three countries in centrality were the United States(0.32),China(0.16),and Canada(0.11).The top three institutions in English literature publications were Johns Hopkins University(51 papers),Ohio State University(39 papers),and Harvard University(38 papers).In China,Sichuan University(32 papers),Huazhong University of Science and Technology(30 papers),and Capital Medical University(27 papers)had multiple English publications;Wuhan University People's Hospital(15 papers),Affiliated Hospital of Guizhou Medical University(13 papers),and Affiliated Hospital of Yan'an University(13 papers)had multiple Chinese publications.There was close collaboration among research institutions in the English literature,whereas Chinese researchers often established research teams within their medical units with relatively less collaboration between teams.(4)Research on ICH surgery primarily focused on surgical methods,complications,and comprehensive perioperative treatment.Research hotspots included hypertensive ICH,minimally invasive surgical techniques,and perioperative management and treatment."neuroendoscopy"was the most recent emergent keyword in Chinese literature with high centrality and the strongest burst strength,while"randomized trial"had the highest burst strength in English literature.Research trends included the integration of artificial intelligence with minimally invasive techniques to optimize ICH surgery management and treatment strategies,analysis of risk factors,and evaluation of imaging value.Conclusions Over the past decade,the overall publication volume on the surgical treatment of ICH has been in a stable development phase,with research directions covering surgical techniques,diagnosis and treatment,evaluation,and management.Core research teams led by key authors were the main contributors to the publications.Future research hotspots and trends in ICH surgery may include the optimization of surgical techniques,complication management,large-scale multicenter clinical trials and integration of artificial intelligence with minimally invasive techniques.
10.Research on the impact of supply side policy coordination of medical insurance on cost control under DIP payment method
Kun-He LIN ; Ye-Sheng SHANGGUAN ; Ya-Qi RAO ; Jing PENG ; Yi CHEN ; Yi-Fan YAO ; Ying-Bei XIONG ; Li XIANG
Chinese Journal of Health Policy 2024;17(5):17-24
Objective:This study aims to explore the synergistic effects of DIP and other medical insurance supply-side policies.Method:City A that has piloted DIP reform was set as the treatment group,and City B without reform was set as the control group.A total of 1 120 public medical institution samples from 2019 to 2022 were collected.The total medical expenses during hospitalization and some structural expenses were analyzed using DID method.Result:DIP had a significant inhibitory effect on the medical expenses,and the expenses of checkups and examinations during hospitalization in city A,but had no impact on the drug and the material expenses during hospitalization.Conclusion:DIP played a significant cost control role and effectively controlled the total medical expenses during hospitalization.The synergistic effects of price adjustment of medical services policy and national centralized drug/material procurement policy on cost control were insufficient.DIP synergized with other supply-side policies to promote rational medical cost structure.It is suggested that medical insurance departments should focus on the synergistic effects of medical insurance supply-side policies to jointly improve the efficiency of medical insurance fund utilization.


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