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panax notoginseng saponins prevent colitis-associated colorectal cancer via inhibition IDO1 mediated immune regulation

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Chinese Journal of Natural Medicines 2022年第4期20卷 258-269页

作者： LI Xue-Ming YUAN Ding-Yi LIU Ya-Hui ZHU Lei QIN Hong-Kun YANG Yu-Bing LI Yan YAN Fang WANG Ya-Jing Department of physiology School of Basic Medicine and Clinical PharmacyChina Pharmaceutical UniversityNanjing 210009China Department of Pharmaceutical Analysis School of pharmacologyChina Pharmaceutical UniversityNanjing 210009China Department of Chronic Communicable Disease Jiangsu Provincial Center for Disease Prevention and ControlNanjing 210009China

Colorectal cancer(CRC)is the third most lethal cancer and leading cause of cancer mortality worldwide.A key driver of CRC development is colon inflammatory responses especially in patients with inflammatory bowl disease(IBD).It has been proved that panax notoginseng saponins(PNS)have anti-inflammatory,anti-oxidant and anti-tumor *** chemopreventive and immunomodulatory functions of PNS on colitis-associated colorectal cancer(CAC)have not been *** present study was designed to study the potential protective effects of PNS on AOM/DSS-induced CAC mice to explore the possible mechanism of PNS against *** study showed that PNS significantly alleviated colitis severity and prevented the occurrence of *** assays revealed that PNS relieved immunosuppression of Treg cells in the CAC microenvironment by inhibiting the expression of IDO 1 mediated directly by signal transducer and activator of transcription 1(STAT1)rather than phosphorylated ***,Rhl,one of the PNS metabolites,exhibited the best inhibitory effect on IDO1 enzyme *** study showed that PNS exerted significant chemopreventive function and immunomodulatory properties on *** could reduce macrophages accumulation and Treg cells differentiation to reshape the immune microenvironment of *** findings provided a promising approach for CAC intervention.

关键词： panax notoginseng saponins Colitis-associated colorectal cancer Chemoprevention Treg cells IDO1

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panax notoginseng saponins Inhibits Ventricular Remodeling after Myocardial Infarction in Rats Through Regulating ATF3/MAP2K3/p38 MAPK and NFκB Pathway

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Chinese Journal of Integrative Medicine 2020年第12期26卷 897-904页

作者： MA Ru-feng CHEN Guang LI Hong-zheng ZHANG Yun LIU Yong-mei HE Hao-qiang LIU Chen-yue XIE Zi-cong ZHANG Zhen-peng WANG Jie Graduate School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing(100029)China Department of Cardiology Guang’anmen HospitalChina Academy of Chinese Medical SciencesBeijing(100053)China

Objective:To explore whether panax notoginseng saponins(PNS)exhibits heart protective effect in myocardial infarction(MI)rats and to identify the potential signaling pathways ***:MI rats induced by ligating the left anterior descending(LAD)coronary artery were assigned to sham coronary artery ligation or coronary artery *** 36 Sprague-Dawley rats were randomly divided into sham group(distilled water,n=9),MI group(distilled water,n=9),PNS group(PNS,40 mg/kg daily,n=9)and fosinopril group(FIP,1.2 mg/kg daily,n=9)according to a random number *** left ventricular morphology and function were conducted by *** alterations were evaluated by the stainings of HE and *** serum levels of C reactive protein(CRP),tumor necrosis factorα(TNF-α),growth differentiation factor-15(GDF-15)and the ratio of metalloproteinase-9(MMP-9)and tissue inhibitor of MMP-9(TIMP-1)were determined by *** levels of activating transcription factor 3(ATF3),mitogen-activated protein kinase kinase 3(MAP2 K3),p38 mitogen-activated protein kinase(p38 MAPK),phosphorylation of p38 MAPK(p-p38 MAPK),transforming growth factor-β(TGF-β1),collagenⅠ,nuclear factor kappa B p65(NFκB p65),phosphorylation of NFκB p65(p-NFκB p65),and phosphorylation of inhibitory kappa Bα(p-IκBα)in hearts were measured by Western blot and immunohistochemical staining,***:PNS improved cardiac function and fibrosis in MI rats(P<0.05).The serum levels of CRP,TNF-α,GDF-15 and the ratio of MMP9/TIMP1 were reversed by PNS in MI *** expressions of TGF-β1,collagenⅠ,MAP2 K3,p38 MAPK,p-p38 MAPK,NFκB p65,p-NFκB p65,and p-IκBαwere down-regulated,while ATF3 increased with the treatment of PNS(P<0.05).Conclusions:PNS may improve cardiac function and fibrosis in MI rats via regulating ATF3/MAP2 K3/p38 MAPK and NFκB signaling *** results suggest the potential of PNS in preventing the development of ventricular remodeling in MI rats.

关键词： panax notoginseng saponins myocardial infarction ventricular remodeling inflammation

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panax notoginseng saponins prevent colitis-associated colorectal cancer development: the role of gut microbiota

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Chinese Journal of Natural Medicines 2020年第7期18卷 500-507页

作者： CHEN Ling CHEN Man-Yun SHAO Li ZHANG Wei RAO Tai ZHOU Hong-Hao HUANG Wei-Hua Department of General Surgery Xiangya HospitalCentral South UniversityChangsha 410008China Department of Clinical Pharmacology Xiangya HospitalCentral South UniversityChangsha 410008China Institute of Clinical Pharmacology Hunan Key Laboratory of PharmacogeneticsCentral South UniversityChangsha 410078China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410008China Department of Pharmacognosy School of PharmacyHunan University of Chinese MedicineChangsha 410128China

Gut microbiota dysbiosis is a risk factor for colorectal cancer(CRC) in inflammatory bowel disease(IBD).In this study, the effects of panax notoginseng saponins(PNS) on colitis-associated CRC progression were evaluated on an azoxymethane(AOM)/dextran sulfate sodium(DSS) mouse *** vivo, PNS significantly relieved AOM/DSS-induced colon tumorigenesis and development by reducing the disease activity index(DAI) scores and colon tumor *** 16S rRNA data of fecal samples showed that the microbiome community was obviously destructed, while PNS could recover the richness and diversity of gut ***, PNS could increase the abundance of Akkermansia *** was significantly decreased in model group and negatively correlated with the progression of ***, ginsenoside compound K(GC-K) was evaluated on the effects of human CRC cells,which was the main bio-transformed metabolite of PNS by gut *** data showed that PNS played important role in the prevention of the progression of CRC, due to their regulation on the microbiome balance and microbial bio-converted product with antiCRC activity.

关键词： panax notoginseng saponins Gut microbiota Colorectal cancer Ginsenosides 16S rRNA gene sequencing

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panax notoginseng saponins preconditioning protects rat liver grafts from ischemia/reper- fusion injury via an antiapoptotic pathway

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Hepatobiliary & Pancreatic Diseases International 2005年第2期4卷 207-212页

作者： Yi Zhang, Qi-Fa Ye, Li Lu, Xian-Lin Xu, Ying-Zi Ming and Jian-Sheng Xiao Wuhan, China Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China Xiangya Transplantation Medical Academy, Third Xiangya Hospital, Xiangya Medi- cal College, Central South University, Changsha 410013, China Institute of Organ Transplantation Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China.

BACKGROUND: Ischemia/reperfusion (I/R) injury is a major cause of primary graft dysfunction and renders an al- lograft more immunogenic in orthotopic liver transplanta- tion (OLT). panax notoginseng saponins (PNS) has been re- ported to exert protective effects against I/R injury to vari- ous organs. The objective of this study is to investigate whether PNS preconditioning protects rat liver grafts from I/R injury via an antiapoptotic pathway. METHODS: Male Sprague-Dawley rats were used as donors and recipients of orthotopic liver transplantation ( OLT) and were divided into PNS preconditioning group (group P) and normal saline control group (group N) randomly according to whether PNS (50 mg/kg) was injected intra- venously 1 hour before liver grafts harvesting, and sham group (group S). The animals were separately killed 2, 6 and 24 hours after reperfusion. Plasma samples were collect- ed for test of alanine amino-transferase (ALT) and aspartate aminotransferase (AST). Liver tissues were collected to de- tect histological changes, apoptosis and the expression of TNF-α, Bcl-2 and Caspase-3 mRNA. RESULTS: The serum levels of ALT and AST and the apop- tosis index (AI) of liver tissue in group P were lower than in group N significantly 2, 6 and 24 hours after reperfusion. Compared with group N, the expression of TNF-a and Caspase-3 mRNA was reduced significantly in group P 2 and 6 hours after reperfusion and the expression of Bcl-2 mRNA was enhanced significantly in group P 6 and 24 hours after reperfusion. CONCLUSIONS: PNS preconditioning protects liver grafts from I/R injury effectively in rat OLT via an antiapoptotic pathway. The antiapoptotic mechanisms of PNS may in- clude inhibiting the expression of TNF-a and Caspase-3 and enhancing the expression of Bcl-2.

关键词： panax notoginseng saponins liver transplantation ischemia/reperfusion injury apoptosis

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panax notoginseng saponins Increases the Blood Concentration of Nifedipine by Inhibiting CYP3A4 Enzyme through PXR-and CAR-Mediated Pathway

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World Journal of Traditional Chinese Medicine 2021年第3期7卷 332-338页

作者： Qiu-Hong Li Jiao Zhao Ai-Xia Ju Yong Hu Qing-Song Qie Hong-Bin Xiao Guang Xu Xi-Jun Wang Clinical Pharmacy Laboratory Department of PharmaceuticsSchool of PharmacyHeilongjiang University of Chinese MedicineHarbinChina 9601 Medical Center Drive RockvilleMDUSA

Objective:To explore the mechanism underlying the effect of panax notoginseng saponins(PNS)on the pharmacokinetics of nifedipine(NF)in *** and Methods:Twenty-four rats were randomly divided into blank(BL)group,PNS group,NF group,and PNS+NF group,with six rats in each *** analysis and t-test were carried out to determine the difference between the pharmacokinetic parameters of NF in different ***3 A4 enzyme activity was calculated using the probe drug *** mRNA and protein contents of CYP3 A4,nuclear receptor CAR,and PXR in rat liver were quantitatively analyzed by qRT-PCR and Western ***:After the rats were treated with the combination of PNS and NF,the plasma concentration,half-life,peak time,and area under the concentration-time curve of NF increased,whereas the clearance rate *** inhibitory effect on CYP3 A4 enzyme activity was in the following order:PNS+NF group(strongest)>PNS group>NF group,and BL group(weakest).Similar changes were observed for the inhibitory effect on CYP3 A4,CAR,and PXR mRNA and protein content,and the order was as follows:PNS+NF group(weakest)

关键词： CAR CYP3A4 nifedipine panax notoginseng saponins pharmacokinetics PXR

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panax notoginseng saponins Inhibits Atherosclerotic Plaque Angiogenesis by Down-Regulating Vascular Endothelial Growth Factor and Nicotinamide Adenine Dinucleotide Phosphate Oxidase Subunit 4 Expression

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Chinese Journal of Integrative Medicine 2015年第4期21卷 259-265页

作者：乔云张鹏举鹿晓婷孙巍巍刘桂林任敏闫磊张继东 Department of Traditional Chinese Medicine Qilu HospitalShandong University Institution of Biochemistry and Molecular Biology Medical School of Shandong University Laboratory of Cardiovascular Remodeling and Function Research Qilu HospitalShandong University Basic Medical College of Shandong University of Traditional Chinese Medicine Second Hospital Shandong University of Traditional Chinese Medicine

Objective： To investigate the mechanism of panax notoginseng saponins （PNS）, an effective component extracted from panax notoginseng, on atherosclerotic plaque angiogenesis in atherosclerosis-prone apolipoprotein E-knockout （ApoE-KO） mice fed with high-fat, high-cholesterol diet. Methods： Twenty ApoE-KO mice were divided into two groups, the model group and the PNS group. Ten normal C57BL/6J mice were used as a control group. PNS （60 mg/kg） was orally administered daily for 12 weeks in the PNS group, The ratio of plaque area to vessel area was examined by histological staining. The tissue sample of aortic root was used to detect the CD34 and vascular endothelial growth factor （VEGF） expression areas by immunohistochemistry. The expression of VEGF and nicotinamide adenine dinucleotide phosphate oxidase subunit 4 （NOX4） were measured by reverse transcription polymerase chain reaction and Westem blotting respectively. Results： After treatment with PNS, the plaque areas were decreased （P〈0.05）. CD34 expressing areas and VEGF expression areas in plaques were significantly decreased （P〈0.05）. Meanwhile, VEGF and NOX4 mRNA expression were decreased after treatment with PNS, VEGF and NOX4 protein expression were also decreased by about 72% and 63%, respectively （P〈0.01）. Conclusion： PNS, which decreases VEGF and NOX4 expression, could alleviate plaque angiogenesis and attenuate atherosclerosis.

关键词： panax notoginseng saponins atherosclerosis plaque angiogenesis vascular endothelial growth factor nicotinamide adenine dinucleotide phosphate oxidase subunit 4

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Targeted trace ingredients coupled with chemometric analysis for consistency evaluation of panax notoginseng saponins injectable formulations

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Chinese Journal of Natural Medicines 2023年第8期21卷 631-640页

作者： ZHANG Jingxian ZHANG Zijia WANG Zhaojun ZHANG Tengqian ZHOU Yang CHEN Ming HUANG Zhanwen HE Qingqing LONG Huali HOU Jinjun WU Wanying GUO Dean National Engineering Research Center of TCM Standardization Technology Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China NMPA Key Laboratory for Quality Control of Traditional Chinese Medicine Shanghai Institute for Food and Drug ControlShanghai 201203China Guangxi Key Laboratory of Comprehensive Utilization Technology of Pseudo-Ginseng Guangxi Zhongheng Innovative Pharmaceutical Research Co.Ltd.Guangxi 530032China School of Pharmacy University of Chinese Academy of SciencesBeijing 100049China

Evaluating the consistency of herb injectable formulations could improve their product quality and clinical safety,particularly concerning the composition and content levels of trace *** notoginseng saponins Injection(PNSI),widely used in China for treating acute cardiovascular diseases,contains low-abundance(10%-25%)and trace saponins in addition to its five main constituents(notoginsenoside R1,ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1,and ginsenoside Rd).This study aimed to establish a robust analytical method and assess the variability in trace saponin levels within PNSI from different vendors and formulation *** achieve this,a liquid chromatography-triple quadrupole mass spectrometry(LC-MS/MS)method employing multiple ions monitoring(MIM)was developed.A“post-column valve switching”strategy was implemented to eliminate highly abundant peaks(NR_(1),Rg_(1),and Re)at 26 min.A total of 51 saponins in PNSI were quantified or relatively quantified using 18 saponin standards,with digoxin as the internal *** study evaluated 119 batches of PNSI from seven vendors,revealing significant variability in trace saponin levels among different vendors and formulation *** findings highlight the importance of consistent content in low-abundance and trace saponins to ensure product control and clinical *** of these ingredients is crucial for maintaining the quality and effectiveness of PNSI in treating acute cardiovascular diseases.

关键词： Consistency evaluation panax notoginseng saponins PCA analysis Xueshuantong Xuesaitong

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panax notoginseng saponins influence on transplantation of neural stem cell-derived dopaminergic neurons in a rat model of Parkinson’s disease

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Neural Regeneration Research 2008年第7期3卷 714-718页

作者： Chunlong Ke Baili Chen Chao Yang Heng Zhang Zhengsong Huang Department of Neurosurgery First Hospital of Sun Yat-sen University Guangzhou 510080 Guangdong Province China Department of Gastroenterology First Hospital of Sun Yat-sen University Guangzhou 510080 Guangdong Province China

BACKGROUND： Dopaminergic neurons differentiated from neural stem cells have been successfully used in the treatment of rat models of Parkinson＇s disease; however, the survival rate of transplanted cells has been low. Most cells die by apoptosis as a result of overloaded intracellular calcium and the formation of oxygen free radicals. OBJECTIVE： To observe whether survival of transplanted cells, transplantation efficacy, and dopaminergic differentiation from neural stem cells is altered by panax notoginseng saponins （PNS） in a rat model of Parkinson＇s disease. DESIGN, TIME AND SETTING： Cellular and molecular biology experiments with randomized group design. The experiment was performed at the Animal Experimental Center, First Hospital of Sun Yat-sen University from April to October 2007. MATERIALS： Thirty-two adult, healthy, male Sprague Dawley rats, and four healthy Sprague Dawley rat embryos at gestational days 14-15 were selected. The right ventral mesencephalon was injected with 6-hydroxydopamine to establish a model of Parkinson＇s disease. 6-hydroxydopamine and apomorphine were purchased from Sigma, USA. METHODS： Neural stem cells derived from the mesencephalon of embryonic rats were cultivated and passaged in serum-free culture medium. Lesioned animals were randomly divided into four groups （n = 8）： dopaminergic neuron, dopaminergic neuron ＋ PNS, PNS, and control. The dopaminergic neuron group was injected with 3 μL cell suspension containing dopaminergic neurons differentiated from neural stem cells. The dopaminergic neurons ＋ PNS group received 3 μ L dopaminergic cell suspension combined with PNS （250 mg/L）. The PNS group received 3 μL PNS （250 mg/L）, and the control group received 3 μL DMEM/F12 culture medium. MAIN OUTCOME MEASURES： The rats were transcardially perfused with 4% paraformaldehyde at 60 days post-grafting for immunohistochemistry. The rats were intraperitoneally injected with apomorphine （0.5 mg/kg） to induce rotational behavior. RESU

关键词： panax notoginseng saponins neural stem cells dopaminergic neurons Parkinson's disease

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panax notoginseng saponins Induced Up-Regulation,Phosphorylation and Binding Activity of MEK,ERK,AKT,PI-3K Protein Kinases and GATA Transcription Factors in Hematopoietic Cells

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Chinese Journal of Integrative Medicine 2013年第2期19卷 112-118页

作者：孙馨高瑞兰林筱洁徐卫红陈小红 Department of Oncology Zhejiang Provincial People's Hospital Institution of Hematology Research The First Affiliated HospitalZhejiang Chinese Medical University

Objective： To investigate the effects of panax notoginseng saponins （PNS） on expression, regulation and phosphorylation of multiple protein kinases in mitogen activated protein kinase （MAPK） intracellular signal pathway and GATA transcription factors in hematopoietic cells, so as to explore its mechanism of proliferation and differentiation activity on hematopoiesis. Methods： The human granulocytic HL-60, erythrocytic K562, megakaryocytic CHRF-288 and Meg-01 cell lines were treated by PNS, the positive control of K562, CHRF-288 ceils treated by recombination human erythropoietin （Epo） and thrombopoietin （Tpo） respectively. The total cell lysate and nuclei protein were extracted after being treated by PNS, subsequently, analyzed by both Western blot and immune-precipitation. Meanwhile, the nuclei extract was performed for electrophoretic mobility shift assay （EMSA） by using 32p radio labeled double-stranded GATA consensus oligonucleotide. Results： The expression levels of kinase MEK-1, MEK-2, ERK-1, ERK-2, AKT-1, AKT-2 and PI- 3K were increased by PNS treatment to different extent in four cell lines, depending on cellular heterogeneity and sensitivity to PNS, also phosphorylation of MEK-1, ERK-1 was differentially promoted by PNS respectively （P〈0.05, 0.01, 0.001）. The expression levels of transcription factors GATA-1 and GATA-2 were increased, moreover, their DNA binding activities were raised dramatically in PNS treated K562, CHRF-288 and Meg-01 cells compared with the controls respectively （P〈0.05, 0.01, 0.001）. The positive control of K562, CHRF-288 cells treated by Epo or Tpo respectively also displayed up-regulation of protein kinases and GATA transcription factors respectively （P〈0.05, 0.01, 0.001）. Conclusion： The results indicated that intracellular signal pathway initiated by PNS was involved in MAPK pathway and transcription factors of GATA family in hematopoietic cells. PNS displayed the role to promote proliferation and differentiation, by means of incre

关键词： panax notoginseng saponins hematopoietic cells protein kinase phosphorylation transcription factor

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Prevention of Deep Vein Thrombosis by panax notoginseng saponins Combined with Low-Molecular-Weight Heparin in Surgical Patients

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Chinese Journal of Integrative Medicine 2022年第9期28卷 771-778页

作者： WANG Chun-mei GUO Xiang-feng LIU Li-min HUANG Ying MENG Liang SONG Li-po WU Ying-feng NING Ya-chan Kathleen H.Reilly WANG Hai-bo Department of Vascular Surgery Xuanwu HospitalCapital Medical UniversityBeijing100053China Children’s Hospital Capital Institute of Pediatrics Beijing100020China Department of Orthopaedics Xuanwu HospitalCapital Medical UniversityBeijing100053China Centers for Disease Control and Prevention New York CityNY12237USA Peking University Clinical Research Institute Peking University First HospitalBeijing100191China

Objective:To evaluate the efficacy of deep vein thrombosis(DVT)prevention among realworld surgical inpatients who received panax notoginseng saponins(PNS)combined with low-molecularweight heparin(LMWH).Methods:A prospective cohort study was conducted among surgical patients between January 2016 and November 2018 in Xuanwu Hospital,Capital Medical University,Beijing,*** received LMWH alone or PNS combined with LMWH for preventing *** primary outcome was incidence of lower extremity DVT,which was screened once a *** in the LMWH group were given LMWH(enoxaparin)via hypodermic injection,4000-8000 AxalU once *** in the exposure group received PNS(Xuesaitong oral tablets,100 mg,3 times daily)combined with LMWH given the same as LMWH ***:Of the 325 patients screened for the study,281 participants were included in the final *** cohort was divided into PNS+LMWH group and LMWH group with 134 and 147 participants,*** was a significant difference of DVT incidence between two groups(P=0.01),with 21(15.7%)incident DVT in the PNS+LMWH group,and 41(27.9%)incident DVT in the LMWH *** with participants without DVT,the participants diagnosed with DVT were older and had higher D-dimer *** multivariate logistic regression moclel showed a significant lower risk of incident DVT among participants in the PNS+LMWH group compared with the LMWH group(odds ratio 0.46,95%confidence interval,0.25-0.86).There were no significant differences in thromboelaslography values(including R,K,Angle,and MA)and differences in severe bleeding between two *** symptomatic pulmonary embolism occurred during the ***:Combined application of PNS and LMWH can effectively reduce the incidence of DVT among surgical inpatients compared with LMWH monotherapy,without increased risk of bleeding.

关键词： panax notoginseng saponins deep vein thrombosis low-molecular-weight heparin thromboelastography risk factor

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