1.Ershen Zhenwu Decoction Treats Chronic Heart Failure by Regulating miR-423-5p/Smad7/TGF-β1/Smads Axis and Myocardial Fibrosis Indicators
Lan GE ; Zhenpeng ZHU ; Xinyue WANG ; Dan CHENG ; Yulong LIU ; Maomao ZHANG ; Xiaoyu CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):157-165
ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure (CHF) due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β1 (TGF-β1)/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF) were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets, sacubitril-valsartan sodium tablets, metoprolol succinate, and spironolactone, and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance, New York Heart Association (NYHA) heart function grade, Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, N-terminal pro-B-type natriuretic peptide (NT-proBNP), angiotensin Ⅱ (Ang Ⅱ), left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs), interventricular septum thickness at diastole (IVSd), left ventricular end-diastolic posterior wall thickness (LVPWd), left ventricular shortening fraction (FS), miR-423-5p, Smad7, Smad2, Smad3, Smad4, TGF-β1, Ang Ⅱ, type Ⅰ collagen (Col Ⅰ), type Ⅲ collagen (Col Ⅲ), mRNA levels of fibronectin (Fn) and α-smooth muscle actin (α-SMA) in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment, both groups showed declined levels of NT-proBNP, Ang Ⅱ, miR-423-5p, Smad2, Smad3, Smad4, TGF-β1, Col Ⅰ, Col Ⅲ, and mRNA levels of Fn and α-SMA (P0.05), and the levels of the indicators above were lower in the observation group than in the control group (P0.05). After treatment, the Smad7 level increased obviously in both groups (P0.05) and was higher in the observation group than in the control group (P0.05). After treatment, both groups showed decreased MLHFQ scores and increased 6-min walking distance (P0.05), and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group (P0.05). After treatment, the control group showed increased LVEF and FS (P0.05) and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS (P0.05). Moreover, the observation group had lower LVIDd and LVIDs (P0.05) and higher LVEF and FS (P0.05) than the control group. The total response rate of cardiac function in the observation group was 90.38% (47/52), which was higher than that (70.59%, 36/51) in the control group (P0.05). No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function, exercise tolerance, and quality of life, regulate neuroendocrine factors, and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF (syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β1/Smads axis, inhibiting α-SMA and Fn expression, and alleviating myocardial fibrosis. It is worthy of further study.
2.Ershen Zhenwu Decoction Treats Chronic Heart Failure by Regulating miR-423-5p/Smad7/TGF-β1/Smads Axis and Myocardial Fibrosis Indicators
Lan GE ; Zhenpeng ZHU ; Xinyue WANG ; Dan CHENG ; Yulong LIU ; Maomao ZHANG ; Xiaoyu CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):157-165
ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure (CHF) due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β1 (TGF-β1)/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF) were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets, sacubitril-valsartan sodium tablets, metoprolol succinate, and spironolactone, and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance, New York Heart Association (NYHA) heart function grade, Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, N-terminal pro-B-type natriuretic peptide (NT-proBNP), angiotensin Ⅱ (Ang Ⅱ), left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs), interventricular septum thickness at diastole (IVSd), left ventricular end-diastolic posterior wall thickness (LVPWd), left ventricular shortening fraction (FS), miR-423-5p, Smad7, Smad2, Smad3, Smad4, TGF-β1, Ang Ⅱ, type Ⅰ collagen (Col Ⅰ), type Ⅲ collagen (Col Ⅲ), mRNA levels of fibronectin (Fn) and α-smooth muscle actin (α-SMA) in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment, both groups showed declined levels of NT-proBNP, Ang Ⅱ, miR-423-5p, Smad2, Smad3, Smad4, TGF-β1, Col Ⅰ, Col Ⅲ, and mRNA levels of Fn and α-SMA (P0.05), and the levels of the indicators above were lower in the observation group than in the control group (P0.05). After treatment, the Smad7 level increased obviously in both groups (P0.05) and was higher in the observation group than in the control group (P0.05). After treatment, both groups showed decreased MLHFQ scores and increased 6-min walking distance (P0.05), and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group (P0.05). After treatment, the control group showed increased LVEF and FS (P0.05) and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS (P0.05). Moreover, the observation group had lower LVIDd and LVIDs (P0.05) and higher LVEF and FS (P0.05) than the control group. The total response rate of cardiac function in the observation group was 90.38% (47/52), which was higher than that (70.59%, 36/51) in the control group (P0.05). No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function, exercise tolerance, and quality of life, regulate neuroendocrine factors, and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF (syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β1/Smads axis, inhibiting α-SMA and Fn expression, and alleviating myocardial fibrosis. It is worthy of further study.
3.Effect of Folic Acid-modified Crebanine Polyethylene Glycol-polylactic Acid Hydroxyacetic Acid Copolymer Nanoparticles Combined with Ultrasonic Irradiation on Subcutaneous Tumor Growth of Liver Cancer in Mice
Rui PAN ; Junze TANG ; Hailiang ZHANG ; Kun YU ; Xiaoyu ZHAO ; Xin CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):217-225
ObjectiveTo investigate the effect of folic acid-modified crebanine polyethylene glycol-polylactic acid hydroxyacetic acid copolymer(PEG-PLGA) nanoparticles(FA-Cre@PEG-PLGA NPs, hereinafter referred to as NPs) combined with ultrasonic irradiation on subcutaneous tumor of liver cancer in Kunming(KM) mice. MethodsEighty-four healthy male KM mice were utilized to establish a subcutaneous tumor model of mouse hepatocellular carcinoma with H22 cells, then mice were randomly divided into model group, placebo group, hydroxycamptothecin group(8 mg∙kg-1), low, medium and high dose crebanine raw material groups(2, 2.5, 3 mg∙kg-1, hereinafter referred to as the low, medium and high dose crebanine groups, respectively), low, medium and high dose NPs groups(2, 2.5, 3 mg∙kg-1), and low, medium and high dose NPs combined with ultrasonic irradiation groups(2, 2.5, 3 mg∙kg-1, hereinafter referred to as the low, medium and high dose combination groups, respectively). The corresponding doses of drugs were administered via tail vein injection, the model group received no treatment, while the placebo group was injected with an equivalent amount of normal saline. Dosing was conducted for a total of 10 times on alternate days. The body mass of the mice was monitored, and parameters such as body mass change rate, thymus index, spleen index, tumor volume, tumor weight, relative tumor growth rate(T/C), and tumor inhibition rate(TGI) were calculated. Pathological changes in liver and kidney tissues as well as the tumor were observed by hematoxylin-eosin(HE) staining. Additionally, the levels of aspartate aminotransferase(AST), alanine aminotransferase(ALT), blood urea nitrogen(BUN) and creatinine(CREA) in serum of mice were detected by biochemical method. Furthermore, the effect of ultrasound on the distribution of NPs in subcutaneous tumors of mouse hepatocellular carcinoma was observed by in vivo imaging technique. ResultsAmong different treatment methods, the combination of NPs and ultrasound irradiation had the best therapeutic effect. Compared with the model group, the body mass growth rates of mice in the medium and high combination groups decreased, while the thymus index and spleen index increased, but there was no statistically significant difference in serum AST, ALT, BUN and CREA levels, indicating that NPs combined with ultrasound irradiation had little effect on the normal physiological state of the body, oth groups had TGI>40% and T/C<60%, indicating a clear anti-tumor effect. Pathological analysis showed that compared with the NPs groups, the combination groups exhibited varying degrees of necrosis in tumor cells, accompanied by less damage to the liver and kidneys. In vivo imaging of small animals showed that compared with the high dose NPs group, the high dose combination group had stronger tumor targeting ability(P<0.01). ConclusionNPs combined with ultrasonic irradiation can not only effectively targeted the drug to the tumor site, inhibit the subcutaneous tumor growth of mouse liver cancer, but also decrease damage to liver and kidney tissues.
4.Prospective study of association between dietary macronutrients and lung function in school aged children
LI Lu, CHEN Mengxue, LI Ruirui, LIU Xueting, WANG Xiaoyu, XU Yujie, XIONG Jingyuan, CHENG Guo
Chinese Journal of School Health 2025;46(2):200-204
Objective:
To explore the longitudinal associations between dietary macronutrients and lung function in schoolaged children, so as to provide the nutritional research evidence for promoting children s lung health.
Methods:
In November 2021, two primary schools located in Chengdu, Sichuan Province were selected from the Southwest China Childhood Nutrition and Growth (SCCNG) cohort by a stratified cluster random sampling method, enrolling a total of 1 112 school aged children aged 8 to 13 years. At baseline, the dietary and sociodemographic characteristics of the children were assessed. One year later, the forced vital capacity (FVC) of the children was measured and converted into Z scores (FVC- Z ), while the vital capacity index (VCI) was also calculated. Generalized linear regression analysis was employed to examine the associations between dietary macronutrients and lung function, considering interactions with gender and age, followed by stratified analysis.
Results:
After adjusting for confounding factors, the analysis results of the generalized linear regression model showed that the carbohydrate energy ratio was negatively correlated with FVC- Z ( β =-0.02) and VCI ( β =-0.16), while the fat energy ratio showed a positive correlation with FVC- Z ( β =0.03) and VCI ( β =0.23) ( P <0.05). The protein energy ratio was positively correlated with FVC- Z ( β =0.09) and VCI ( β =0.60) specifically in girls ( P <0.05). Additionally, there was an interaction effect of age on the associations between macronutrients and lung function ( P <0.01); in children aged 8-9 and 10-11, the carbohydrate energy supply ratio was negatively correlated with FVC- Z ( β =-0.04, -0.03) and VCI ( β =-0.29, -0.21), and fat energy supply ratio was positively correlated with FVC- Z ( β =0.07, 0.05) and VCI ( β =0.46, 0.32) ( P <0.05).
Conclusions
There are age and sex differences in the association of dietary macronutrients with lung function, with a low carbohydrate, high fat diet promoting lung function in children. Additionally, protein intake appears to have a positive influence on the lung function of girls. The early school age period may represent a critical window for dietary interventions aimed at promoting lung health.
5.Targeting effect and anti-tumor mechanism of folic acid-modified crebanine nanoparticles combined with ultra-sound irradiation on M109 cells in vitro and in vivo
Hailiang ZHANG ; Xiaoyu ZHAO ; Jiahua MEI ; Rui PAN ; Junze TANG ; Kun YU ; Rui XUE ; Xiaofei LI ; Xin CHENG
China Pharmacy 2025;36(14):1730-1736
OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles (FA-Cre@PEG- PLGA NPs, hereinafter referred to as “NPs”) combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration, and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells, and the best ultrasound time was selected. Using human lung cancer A549 cells as a control, the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration, invasion, apoptosis, cell cycle and reactive oxygen species (ROS) levels of M109 cells were detected by cell scratch test, Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration; the changes of mitochondrial membrane potential (MMP) were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed, and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells, and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells, and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells, the uptake rate of NPs in M109 cells was significantly higher (P<0.01), and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group, the apoptosis rate of M109 cells and ROS level were increased significantly (P<0.01), while the MMP decreased significantly (P<0.01) in the different concentration (100, 200, 300 μg/mL) groups of M109 cells. Compared with the mice in non-ultrasound group, the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced (P<0.05 or P<0.01). CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo, the anti-tumor mechanism includes inhibiting cell migration and invasion, blocking cell cycle, and inducing apoptosis.
6.Rules of moxibustion for low back pain by ZHOU Meisheng based on data mining and knowledge graph technology.
Chi WANG ; Caifeng ZHU ; Jiayu ZHANG ; Bingyuan ZHOU ; Xiaoyu CHEN ; Le CHENG ; Miaomiao XIE ; Xuechun DING
Chinese Acupuncture & Moxibustion 2025;45(6):823-833
OBJECTIVE:
To analyze the rules of moxibustion for low back pain by ZHOU Meisheng by using data mining and knowledge graph technology.
METHODS:
Taking the medical cases of moxibustion for low back pain from ZHOU Meisheng's legacy manuscripts and existing works as the research objects, information on disease types, symptoms, tongue manifestations, pulse conditions, syndrome patterns, moxibustion methods and acupoints were collected. Frequency statistics and community analysis were conducted by the ancient and modern medical record cloud platform V 2.3.7, cluster analysis of high-frequency acupoints was performed by SPSS26.0, association rule analysis of high-frequency acupoints was performed by SPSS Modeler 18.0, and the generated linked data were imported into Cytoscape 3.9.1 for complex network analysis. Knowledge graph of moxibustion for low back pain by ZHOU Meisheng was constructed based on the results of data mining. The data storage and display of knowledge graph were realized through the Neo4j 3.5.25 graph database, and the Cypher query language was used for knowledge graph retrieval and discovery.
RESULTS:
A total of 219 medical cases were collected, involving 14 disease types, 85 related clinical symptoms, 5 related TCM syndrome types, and 6 moxibustion methods. The acupoints were mostly attributed to the governor vessel, the bladder meridian of foot-taiyang, non-meridian and non-acupoint areas. The core prescription of acupoints derived from complex network analysis included tender points, Shenshu (BL23), Jinsuo (GV8), Yinjiao (CV7), Yaoyangguan (GV3), Yanglingquan (GB34), which were largely coincides with high-frequency acupoints. Cluster analysis obtained 4 cluster combinations. Community analysis yielded 6 communities, each corresponding to different acupoints.The constructed knowledge graph contained 187 nodes and 696 relationships, by retrieving clinical elements related to low back pain, the disease-moxibustion association graph, disease-acupoint association graph, accompanying symptom-acupoint association graph and syndrome type-matching point association graph were obtained.
CONCLUSION
When treating low back pain with moxibustion, ZHOU Meisheng adopts the principle of promoting circulation, distinguishing diseases to determine the treatment, selecting acupoints according to the diseases, and matching points according to the symptoms.And taking tender points, Shenshu (BL23), Jinsuo (GV8), Yinjiao (CV7), Yaoyangguan (GV3), Yanglingquan (GB34) as core acupoints, combined with tenderness point selection, acupoint selection based on meridian and zangfu syndrome differentiation, "sunshine area" acupoint selection, yin-yang acupoint matching. Additionally, he skillfully employs special points, such as Zhongzhu (KI15) and ear tips, pays attention to the reform of moxibustion tools, and innovates the moxibustion techniques, using distinctive moxibustion tools and methods to treat low back pain.
Moxibustion/methods*
;
Humans
;
Data Mining
;
Low Back Pain/history*
;
Acupuncture Points
;
History, Ancient
;
Female
;
China
;
Male
;
Adult
;
Middle Aged
7.Therapeutic role of miR-26a on cardiorenal injury in a mice model of angiotensin-II induced chronic kidney disease through inhibition of LIMS1/ILK pathway.
Weijie NI ; Yajie ZHAO ; Jinxin SHEN ; Qing YIN ; Yao WANG ; Zuolin LI ; Taotao TANG ; Yi WEN ; Yilin ZHANG ; Wei JIANG ; Liangyunzi JIANG ; Jinxuan WEI ; Weihua GAN ; Aiqing ZHANG ; Xiaoyu ZHOU ; Bin WANG ; Bi-Cheng LIU
Chinese Medical Journal 2025;138(2):193-204
BACKGROUND:
Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD.
METHODS:
We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data.
RESULTS:
Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes.
CONCLUSIONS
Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals
;
MicroRNAs/metabolism*
;
Angiotensin II/toxicity*
;
Mice
;
Renal Insufficiency, Chronic/chemically induced*
;
Mice, Knockout
;
Disease Models, Animal
;
Male
;
Signal Transduction/genetics*
;
LIM Domain Proteins/genetics*
;
Mice, Inbred C57BL
;
Cell Line
;
Humans
8.Efficacy and safety of avatrombopag in the treatment of thrombocytopenia after umbilical cord blood transplantation.
Aijie HUANG ; Guangyu SUN ; Baolin TANG ; Yongsheng HAN ; Xiang WAN ; Wen YAO ; Kaidi SONG ; Yaxin CHENG ; Weiwei WU ; Meijuan TU ; Yue WU ; Tianzhong PAN ; Xiaoyu ZHU
Chinese Medical Journal 2025;138(9):1072-1083
BACKGROUND:
Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
METHODS:
We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation.
RESULTS:
Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z = 2.095, P = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P = 0.003).
CONCLUSION
Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans
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Female
;
Male
;
Thrombocytopenia/etiology*
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Adult
;
Retrospective Studies
;
Cord Blood Stem Cell Transplantation/adverse effects*
;
Middle Aged
;
Adolescent
;
Young Adult
;
Thiazoles/adverse effects*
;
Platelet Count
;
Receptors, Thrombopoietin/agonists*
;
Child
;
Thiophenes
9.Itaconate derivative 4-OI inhibits M1 macrophage polarization and restores its impaired function in immune thrombocytopenia through metabolic reprogramming.
Qiang LIU ; Anli LIU ; Shaoqiu LENG ; Xiaoyu ZHANG ; Xiaolin WANG ; Zhang CHENG ; Shuwen WANG ; Jun PENG ; Qi FENG
Chinese Medical Journal 2025;138(16):2006-2015
BACKGROUND:
Macrophage polarization anomalies and dysfunction play a crucial role in the pathogenesis of immune thrombocytopenia (ITP). Itaconate is a Krebs cycle-derived immunometabolite synthesized by myeloid cells to modulate cellular metabolism and inflammatory responses. This study aimed to evaluate the immunoregulatory effects of an itaconate derivative on macrophages in patients with ITP.
METHODS:
Peripheral blood-derived macrophages from patients with ITP and healthy controls were treated with 4-octyl itaconate (4-OI), a derivative of itaconate that can penetrate the cell membrane. Macrophage polarization, antigen-presenting functions, and phagocytic capability were measured via flow cytometry and enzyme-linked immunosorbent assay (ELISA). Macrophage glycolysis in patients with ITP and the metabolic regulatory effect of 4-OI were detected using a Seahorse XFe96 Analyzer. An active murine model of ITP was used to evaluate the therapeutic effects of 4-OI in vivo .
RESULTS:
4-OI reduced the levels of CD80 and CD86 in M1 macrophages and suppressed the release of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 pro-inflammatory cytokines, suggesting that 4-OI could hinder the polarization of macrophages toward an M1 phenotype. We found that 4-OI pretreated M1 macrophages reduced the proliferation of CD4 + T cells and promoted the differentiation of regulatory T cells. In addition, after 4-OI treatment, the phagocytic capacity of M1 macrophages toward antibody-coated platelets decreased significantly in patients with ITP. In addition, the glycolytic function of M1 macrophages was elevated in individuals with ITP compared to those in healthy controls. 4-OI treatment downregulated glycolysis in M1 macrophages. The glycolysis inhibitor 2-deoxy-d-glucose (2-DG) also inhibited the polarization of M1 macrophages and restored their functions. In vivo , 4-OI treatment significantly increased platelet counts in the active ITP murine model.
CONCLUSIONS
Itaconate derivative 4-OI inhibited M1 macrophage polarization and restored impaired functions through metabolic reprogramming. This study provides a novel therapeutic option for ITP.
Macrophages/metabolism*
;
Humans
;
Animals
;
Succinates/pharmacology*
;
Mice
;
Male
;
Female
;
Adult
;
Middle Aged
;
Flow Cytometry
;
Tumor Necrosis Factor-alpha/metabolism*
;
Enzyme-Linked Immunosorbent Assay
;
Purpura, Thrombocytopenic, Idiopathic/metabolism*
;
Glycolysis/drug effects*
;
Metabolic Reprogramming
10.Incidence, mortality, and burden of Parkinson's disease in China: A time-trend analysis and comparison with the global burden based on Global Burden of Disease Study 2021.
Fan GAO ; Xiaoyu CHENG ; Junyi LIU ; Yinlian HAN ; Chengjie MAO ; Chongke ZHONG ; Chunfeng LIU
Chinese Medical Journal 2025;138(23):3176-3183
BACKGROUND:
Parkinson's disease (PD) is a leading cause of death and disability worldwide, and is associated with a significant Global Burden of Disease (GBD). We analyzed the trends in PD incidence, mortality, and disability-adjusted life year (DALY) burden in China, and compared them with global data.
METHODS:
Estimates and 95% uncertainty intervals (UIs) for incidence, mortality, DALYs, years lived with disability (YLDs), and years of life lost (YLLs) for PD were extracted from the GBD, Injuries, and Risk Factors Study 2021. We describe the epidemiology of PD at global and Chinese levels, analyze trends in incidence and mortality from 1990 to 2021 by joinpoint regression models, and decompose PD burden according to population size, age structure, and epidemiological changes.
RESULTS:
GBD 2021 estimated 508,378 (95% UI: 430,499-592,748) incident cases of PD, 92,035 (95% UI: 75,908-108,133) deaths, and 2,159,514 (95% UI: 1,826,196-2,521,344) DALYs in China, with the higher age-standardized rate (ASR) in incidence, mortality and DALYs than the global levels. The DALY burden of PD in China increased slightly from 1990 to 2021, consistent with the global upward trend. Joinpoint regression analysis indicated that the ASR of incidence in China increased faster than the global average, while the ASR of mortality decreased, with the fastest decline in 2004-2014. Decomposition analysis revealed that men and the middle sociodemographic index (SDI) quintile (32.82%) were responsible for the most significant DALYs, whose changes were primarily driven by population growth and aging.
CONCLUSIONS
The burden of PD showed an overall increasing trend from 1990 to 2021, which was primarily driven by population growth and aging. This study highlights the significant challenges in controlling and managing PD, including the increase in cases and gender differences, which may provide guidance for comprehensive strategies to address the changing profiles of PD in China.
Humans
;
Parkinson Disease/mortality*
;
China/epidemiology*
;
Global Burden of Disease
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Male
;
Incidence
;
Female
;
Disability-Adjusted Life Years
;
Middle Aged
;
Aged
;
Adult
;
Quality-Adjusted Life Years
;
Aged, 80 and over
;
Cost of Illness
;
Adolescent
;
Pattern Analysis, Machine


Result Analysis
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