1.Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways.
Ying HUANG ; Chen-Ling CHU ; Wen-Hui QIU ; Jia-Yi CHEN ; Lu-Xi CAO ; Shui-Yu JI ; Bin ZHU ; Guo-Kun WANG ; Quan-Quan SHEN
Journal of Integrative Medicine 2025;23(6):694-705
OBJECTIVE:
Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF.
METHODS:
The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial-mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations.
RESULTS:
Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2'-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells.
CONCLUSION
AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF. Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694-705.
Epithelial-Mesenchymal Transition/drug effects*
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Animals
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Saponins/pharmacology*
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Triterpenes/pharmacology*
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Mice
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Peritoneal Fibrosis/pathology*
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Proto-Oncogene Proteins c-akt/metabolism*
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ErbB Receptors/metabolism*
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Phosphatidylinositol 3-Kinases/metabolism*
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Signal Transduction/drug effects*
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Male
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Humans
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Molecular Docking Simulation
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Cell Line
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Mice, Inbred C57BL
2.Efficacy and safety of a facilitated percutaneous coronary intervention with half-dose recombinant staphylokinase in ST-segment elevation myocardial infarction
Tian-yu WU ; Wen-hao ZHANG ; Peng-sheng CHEN ; Chen LI ; Tian WU ; Zhan LÜ ; Tong WANG ; Kun LIU ; Zhi-wen TAO ; Xiao-xuan GONG ; Liang YUAN ; Yong LI ; Bo CHEN ; Xin CHEN ; Zeng-guang CHEN ; Nai-quan YANG ; Yuan-yuan SANG ; Xiao-yan WANG ; Bai-hong LI ; Li ZHU ; Guo-yu WANG ; Xin ZHAO ; Chuan LU ; Jun JIANG ; Rui-na HAO ; Chun-jian LI
Chinese Journal of Interventional Cardiology 2025;33(8):431-438
Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P<0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P>0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.
3.Efficacy and safety of a facilitated percutaneous coronary intervention with half-dose recombinant staphylokinase in ST-segment elevation myocardial infarction
Tian-yu WU ; Wen-hao ZHANG ; Peng-sheng CHEN ; Chen LI ; Tian WU ; Zhan LÜ ; Tong WANG ; Kun LIU ; Zhi-wen TAO ; Xiao-xuan GONG ; Liang YUAN ; Yong LI ; Bo CHEN ; Xin CHEN ; Zeng-guang CHEN ; Nai-quan YANG ; Yuan-yuan SANG ; Xiao-yan WANG ; Bai-hong LI ; Li ZHU ; Guo-yu WANG ; Xin ZHAO ; Chuan LU ; Jun JIANG ; Rui-na HAO ; Chun-jian LI
Chinese Journal of Interventional Cardiology 2025;33(8):431-438
Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P<0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P>0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.
4.Isoflavones from Sojae Semen Praeparatum Regulate Lipid Metabolism in Atherosclerotic Mice Through PPARγ/LXRα/ABCA1 Signaling Pathway
Jing-xin MA ; Jin-zhou GUO ; Hai-ning CHEN ; Ke XIE ; De-sen QUAN ; Jing-yan DU ; Lin-xiao LIU ; Qi YU ; Wei-yi TIAN ; Kun CAI
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(11):110-118
ObjectiveTo study the effect of isoflavones from Sojae Semen Praeparatum (ISSP) on lipid metabolism in atherosclerotic mice, and decipher the underlying mechanism via the peroxisome proliferator-activated receptor gamma/liver X receptor alpha/ATP-binding cassette transporter A1 (PPARγ/LXRα/ABCA1) signaling pathway. MethodFifty ApoE-/- mice were randomly assigned into the model group, western medicine (atorvastatin calcium, 3.03 mg·kg-1) group, and low-, medium-, and high-dose ISSP (2.5, 5, 10 mg·kg-1, respectively) groups, with 10 rats in each group. Atherosclerosis model mice were established by bilateral ovariectomy and feeding high-fat diet. Another 10 ApoE-/- mice receiving ovariectomy and high-fat diet were taken as the sham group. Some mice died of postoperative infection, and finally 6 mice were included in each group. One week after operation, each group was administrated with corresponding drugs or equivalent amount of normal saline. After 12 weeks, the levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and non-esterified fatty acids (NEFAs) in serum and liver tissue were measured. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum were detected by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining and oil red O staining were used for observation of aortic plaque formation and liver lipid deposition. The mRNA and protein levels of PPARγ, LXRα, ABCA1, and ATP-binding cassette transporter G1 (ABCG1) in liver were determined by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot. ResultCompared with the sham group, the modeling of atherosclerosis increased the aortic plaque area (P<0.01), elevated the serum TC, TG, LDL-C, TNF-α, and IL-6 levels (P<0.01), decreased the level of HDL-C (P<0.01), increased the liver index (P<0.05) and the levels of TC, TG, and NEFAs in liver (P<0.01), and caused obvious hepatic fat vacuoles and lipid deposition. In addition, the modeling down-regulated the mRNA levels of PPARγ, LXRα, ABCA1 in liver (P<0.05, P<0.01),and regulated the mRNA and protein levels of ABCG1(P<0.05, P<0.01). Compared with the model group, atorvastatin calcium and middle-, high-dose ISSP reduced the serum TC, TG, LDL-C, TNF-α, and IL-6 levels (P<0.01), decreased the liver index (P<0.01), alleviated the liver fat vacuoles and lipid deposition, and increased the levels of TC, TG, and NEFAs in the liver (P<0.05, P<0.01). Furthermore, they up-regulated the mRNA and protein levels of PPARγ, LXRα, ABCA1, and ABCG1 in the liver (P<0.05, P<0.01). ConclusionISSP may regulate lipid metabolism through PPARγ/LXRα/ABCA1 signaling pathway to down-regulate the expression of inflammatory cytokines in serum and alleviate liver lipid deposition, thereby suppressing the formation of atherosclerotic plaque.
5. Expression and clinical significance of phosphoglycerate kinase 1 in hepatocellular carcinoma based on bioinformatics methods
Cheng-Jian GUAN ; Hua-Jing YU ; Xiao-Dong ZHANG ; Quan RAO ; Wei-Tao ZHANG ; Kun LIU ; Hong-Wei WU ; Dong WANG ; Zhong-Tao ZHANG ; Wei GUO
Acta Anatomica Sinica 2022;53(6):744-753
Objective To investigate the role of phosphoglycerate kinase 1 (PGK1) in tumorigenesis and its potential post-translational modification sites were investigated by bioinformatics method and molecular biology experimental techniques, in order to provide evidence for PGK1 as a hepatocellular carcinoma ( HCC) diagnostic biomarker and therapeutic target. Methods From pan-cancer's point of view, 10 967 samples were obtained from the cancer genome database TCGAs, and the expression of PGK1 in different tumors was explored by using cBioPortal and UALCAN analysis tools; Focusing on HCC, the expression differences of PGK1 in hepatocellular carcinoma tumor tissues and normal tissues were further analyzed by using GEO database analysis, Real-time PCR, Western blotting and cell invasion assay;The String database was used to analyze the protein-protein interaction network and gene set enrichment analysis; The CSS-Palm database and bioinformatics method were used to predict protein post-translational modification sites on PGK1. Results The PGK1 gene was abnormally amplified and overexpressed in various solid tumors, including hepatocellular carcinoma, and overexpression of PGK1 was correlated with a poor prognosis in hepatocellular carcinoma. Multiple novel posttranslational modifications were existed on PGK1. Conclusion PGK1 is closely related to the occurrence and development of various cancers including HCC and glycolytic metabolism abnormalities. Epigenetic modifications can regulate PGK1 and affect its cellular function in HCC.
6.Extraction and separation, structure analysis and biological activity of polysaccharides from Atractylodis Rhizoma.
Li-Kun CHANG ; Wen-Jin ZHANG ; Ye CAO ; Sheng WANG ; Chuan-Zhi KANG ; Li ZHOU ; Quan YANG ; Liang-Yun ZHOU ; Lan-Ping GUO
China Journal of Chinese Materia Medica 2021;46(9):2133-2141
Atractylodis Rhizoma(AR) is a traditional Chinese medicinal material for food and medicine, with the functions of eli-minating dampness, strengthening the spleen, expelling wind evil and dispersing cold. AR contains a variety of compounds, including sesquiterpenoids, alkynes, triterpenoids, aromatic glycosides, polysaccharides and so on. At present, the researches on AR mainly focus on volatile components, with relatively fewer researches on non-volatile components. Polysaccharide from Atractylodis Rhizoma(ARP) is an important material basis among non-volatile components for the efficacy. Due to its many biological activities such as immunomodulatory activity, anti-tumors, anti-virus and anti-oxidation, ARP has certain research value and potential. The diversity of the polysaccharide structure is the basis for biological functions, but it also increases the difficulty of carbohydrate research. The research on the extraction, separation, purification, structure and activity of ARP is in the preliminary exploration stage, still with many shortcomings. Herein, recent advancements in the extraction, purification, structural characteristics and biological activities of ARP were summarized in this article to provide scientific reference for the in-depth systematic research of ARP and the development of AR resources.
Atractylodes
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Drugs, Chinese Herbal
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Polysaccharides
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Rhizome
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Triterpenes
7.The Advantages and Disadvantages of Computer Simulation in the Teaching of Abdominal Diagnosis
Hua-mei WU ; Yun-juan YANG ; Ying XU ; Guo-bin LIU ; Shu-kun WANG ; Jing-xing YU ; Song-quan HUANG
Journal of Kunming Medical University 2018;39(6):128-131
Objective To compare the effectivenessbetween the use of computer simulationin the teaching of abdomen diagnosis skills and the traditional teaching mode by conducting the real-time assessment and after-school questionnaire survey. Method Weselected 308 undergraduates with 165 (4 classes) majoring in clinical medicine and 143 (4 classes) majoring in medical laboratory in Kunming Medical Universityas the research object. Students were randomly divided into two groups and taught using demonstration method. One group practiced abdominal examination on other students while the other group adopted computer simulation.Both groups were giventests of practical skills and anonymous open-ended questionnaires after class.Results The average score of computer simulation group was higher than the other group. The questionnaire survey showed that computer simulation was suitable for repeatable exercises and easy to review after class (P<0.05).Conclusion In thediagnostic practice of abdominal examination,teaching assisted with computer simulation showing an outstanding performance should be combined and promoted with the traditional teaching.
8.Design and Application of Queuing & Calling System in Complex Environment of Specialized Hospitals
quan Jian HE ; cheng Guo RUAN ; qiang Zheng YE ; kun Mu XIAO ; li Li WANG
Journal of Medical Informatics 2017;38(11):31-33
From the perspective of information technology,the paper designes and implementes the queuing & calling system in the complex environment of specialized hospitals according to actual circumstances and characteristics of out-patient and examination areas,and introduces the architecture,operating process,comparison of effects before and after the optimization,specific application of the system.After launched and used,the system can improve the order in various areas and enhance the satisfaction of both doctors and patients.
9.Exploration and optimization of processes for key intermediates of phosphorodiamidate morpholino oligonucleotides
rui Xiao CHEN ; jian Yong GUO ; bin Ya SONG ; na Dong ZHANG ; kun LI XU ; gang Bao WANG ; yuan Yuan DOU ; quan Hong WANG
Military Medical Sciences 2017;41(8):662-666
Objective To explore and optimize the processes for synthesis of key intermediates of phosphorodiamidate morpholino oligonucleotides-7'-hydroxy-N-trityl morpholino nucleoside monomer in order to contribute to the research of phosphorodiamidate morpholino oligonucleotides antisense nucleotides.Methods With N-benzoylcytidine,guanosine and 5-methyluridine as starting materials,the ribose was modified to morpholino and the key chemical groups were protected to obtain 7'-hydroxy-N-trityl morpholino nucleoside monomer.Results Compounds N4-benzoyl-7'-hydroxy-N-trityl morpholinocytidine,N2-benzoyl-7'-hydroxy-N-trityl morpholinoguanosine and 7'-hydroxy-N-trityl morpholinothymidine were synthesized.The synthetic processes were optimized as well.The structures of all the intermediates and title compounds were characterized.Conclusion The synthetic processes of 7'-hydroxy-N-trityl morpholino nucleoside monomers have been optimized,which can be employed to prepare title compounds on a large scale.
10.Current status and urban-rural comparison of clinical agency of detection, management, and health insurance for hypertensive patients in communities of five provinces in China in 2010.
Jian-xin LI ; Xiao-hua LIANG ; Jie CAO ; Kun ZHU ; Ying DENG ; Zheng-yuan ZHOU ; Yi WANG ; Guo-sheng WAN ; Chuan ZHAO ; Quan-cheng MU ; Fang-hong LU ; Dong-feng GU
Chinese Journal of Preventive Medicine 2013;47(4):301-305
OBJECTIVETo investigate the status of the clinical agency of detection, management, and health insurance for hypertensive patients in urban and rural communities of five provinces in China in 2010, in order to provide fundamental data for implementation and evaluation of community health management of hypertensive patients in basic public health service.
METHODSFrom Jiangsu, Shandong, Hebei, Sichuan and Gansu provinces, cities and districts (counties) were selected according to economic development level and 10 survey sites were finally determined. In each survey site, 3-4 communities or townships were selected by cluster sampling methods in 2010. A total of 8326 eligible hypertensive patients (4363 in urban and 3963 in rural) were included. The urban-rural difference of clinical agency and health insurance was compared for hypertensive patients.
RESULTSIn urban areas, 43.74% (1867/4268) hypertensive patients were first diagnosed at hospitals of district level or above, 25.07% (1070/4268) at community health service centers (CHSC), and 20.20% (862/4268) at community health service stations (CHSS), respectively; 30.72% (1274/4147) and 31.11% (1290/4147) patients chose CHSC and CHSS for their follow-up visiting, respectively; 60.23% (3073/5102) antihypertensive medication was obtained from pharmacies. In rural areas, 54.58% (2133/3908) hypertensive patients were first diagnosed at village clinics, 22.36% (874/3908) at township hospitals, and 18.86% (737/3908) at hospitals of county level or above; 70.49% (2695/3823) patients chose village clinics for their follow-up visiting; 46.23% (2116/4577) antihypertensive medication was obtained from village clinics, and 36.29% (1661/4577) from pharmacies. The main reasons for choosing clinical agency for both urban and rural patients were convenience (45.79%, 6276/13 706) and low cost (11.78%, 1614/13 706). The proportions of reimbursements for hospitalization expenses and total medical expenses for hypertensive patients in urban in the past year were 66.67% and 34.78%, respectively, which were much higher than those in rural (35.71% and 9.50%) (Z value was -12.13 and -17.56, P < 0.01).
CONCLUSIONCommunity-based hypertension detection and routine blood pressure measurement during clinical visiting should be further strengthened to improve early diagnosis of hypertension. The development of community-based clinical agency should be able to provide convenient and low cost health service for hypertensive patients to improve treatment, follow-up and control of hypertension.
Adult ; Aged ; China ; Cities ; Community Health Services ; Female ; Humans ; Hypertension ; diagnosis ; therapy ; Insurance, Health ; Male ; Middle Aged ; Public Health ; Rural Health Services ; Urban Health Services

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