{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:59:11Z","timestamp":1790351951139,"version":"4.1.0"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["2017YFC1700200"],"award-info":[{"award-number":["2017YFC1700200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973706"],"award-info":[{"award-number":["81973706"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Chin Med"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Traditional Chinese Medicine (TCM) is distinguished by Syndrome differentiation, which prescribes various formulae for different Syndromes of same disease. This study aims to investigate the underlying mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using a strategy which integrated proteomics, metabolomics study for clinic samples and network pharmacology for six classic TCM formulae, we systemically explored the biological basis of TCM Syndrome differentiation for two typical Syndromes of CHD: Cold Congealing and Qi Stagnation (CCQS), and Qi Stagnation and Blood Stasis (QSBS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our study revealed that CHD patients with CCQS Syndrome were characterized with alteration in pantothenate and CoA biosynthesis, while more extensively altered pathways including D-glutamine and D-glutamate metabolism; alanine, aspartate and glutamate metabolism, and glyoxylate and dicarboxylate metabolism, were present in QSBS patients. Furthermore, our results suggested that the down-expressed PON1 and ADIPOQ might be potential biomarkers for CCQS Syndrome, while the down-expressed APOE and APOA1 for QSBS Syndrome in CHD patients. In addition, network pharmacology and integrated analysis indicated possible comorbidity differences between the two Syndromes, that is, CCQS or QSBS Syndrome was strongly linked to diabetes or ischemic stroke, respectively, which is consistent with the complication disparity between the enrolled patients with two different Syndromes. These results confirmed our assumption that the molecules and biological processes regulated by the Syndrome-specific formulae could be associated with dysfunctional objects caused by the Syndrome of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study provided evidence-based strategy for exploring the biological basis of Syndrome differentiation in TCM, which sheds light on the translation of TCM theory in the practice of precision medicine.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13020-021-00521-3","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T18:02:42Z","timestamp":1635271362000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Exploring biological basis of Syndrome differentiation in coronary heart disease patients with two distinct Syndromes by integrated multi-omics and network pharmacology strategy"],"prefix":"10.1186","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7548-1588","authenticated-orcid":false,"given":"Gaosong","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nixue","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningning","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingfang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieqiong","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengfei","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxu","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houkai","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,26]]},"reference":[{"key":"521_CR1","doi-asserted-by":"crossref","first-page":"484201","DOI":"10.1155\/2014\/484201","volume":"2014","author":"SB Su","year":"2014","unstructured":"Su SB, Jia W, Lu A, Li S. Evidence-based zheng: a traditional chinese medicine syndrome 2013. Evid Based Complement Alternat Med. 2014;2014:484201.","journal-title":"Evid Based Complement Alternat Med."},{"key":"521_CR2","first-page":"246538","volume":"2012","author":"SB Su","year":"2012","unstructured":"Su SB, Lu A, Li S, Jia W. Evidence-based zheng: a traditional chinese medicine syndrome. Evid Based Complement Alternat Med. 2012;2012:246538.","journal-title":"Evid Based Complement Alternat Med."},{"issue":"8","key":"521_CR3","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1007\/s11655-012-1172-1","volume":"18","author":"ZZ Wang","year":"2012","unstructured":"Wang ZZ, Fang YF, Wang Y, Mu FX, Chen J, Zou QH, et al. Logistic regression analysis of damp-heat and cold-damp impeding syndrome of rheumatoid arthritis: a perspective in Chinese medicine. Chin J Integr Med. 2012;18(8):575\u201381.","journal-title":"Chin J Integr Med"},{"issue":"1","key":"521_CR4","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1049\/iet-syb:20060032","volume":"1","author":"S Li","year":"2007","unstructured":"Li S, Zhang ZQ, Wu LJ, Zhang XG, Li YD, Wang YY. Understanding Zheng in traditional Chinese medicine in the context of neuro-endocrine-immune network. IET Syst Biol. 2007;1(1):51\u201360.","journal-title":"IET Syst Biol"},{"key":"521_CR5","doi-asserted-by":"publisher","first-page":"105034","DOI":"10.1016\/j.phrs.2020.105034","volume":"159","author":"J Yang","year":"2020","unstructured":"Yang J, Tian S, Zhao J, Zhang W. Exploring the mechanism of TCM formulae in the treatment of different types of coronary heart disease by network pharmacology and machining learning. Pharmacol Res. 2020;159:105034.","journal-title":"Pharmacol Res."},{"issue":"12","key":"521_CR6","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1016\/j.jacc.2016.06.044","volume":"68","author":"Y Fan","year":"2016","unstructured":"Fan Y, Li Y, Chen Y, Zhao YJ, Liu LW, Li J, et al. Comprehensive metabolomic characterization of coronary artery diseases. J Am Coll Cardiol. 2016;68(12):1281\u201393.","journal-title":"J Am Coll Cardiol"},{"key":"521_CR7","first-page":"714517","volume":"2012","author":"Y Ren","year":"2012","unstructured":"Ren Y, Zhang M, Chen K, You S, Li J, Guo L, et al. Clinical and epidemiological investigation of tcm syndromes of patients with coronary heart disease in China. Evid Based Complement Alternat Med. 2012;2012:714517.","journal-title":"Evid Based Complement Alternat Med."},{"issue":"1","key":"521_CR8","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s40484-019-0167-8","volume":"7","author":"J Zhao","year":"2019","unstructured":"Zhao J, Yang J, Tian S, Zhang W. A survey of web resources and tools for the study of TCM network pharmacology. Quant Biol. 2019;7(1):17\u201329.","journal-title":"Quant Biol"},{"key":"521_CR9","doi-asserted-by":"publisher","first-page":"153315","DOI":"10.1016\/j.phymed.2020.153315","volume":"85","author":"J Zhao","year":"2021","unstructured":"Zhao J, Tian S, Lu D, Yang J, Zeng H, Zhang F, et al. Systems pharmacological study illustrates the immune regulation, anti-infection, anti-inflammation, and multi-organ protection mechanism of qing-fei-pai-du decoction in the treatment of covid-19. Phytomedicine. 2021;85:153315\u201315.","journal-title":"Phytomedicine"},{"key":"521_CR10","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.phrs.2018.07.020","volume":"135","author":"W Xu","year":"2018","unstructured":"Xu W, Zhang Y, Yu Y, Li B, Liu J, Wang P, et al. Dose-dependent target diversion of Danhong injection on the Glu-GLT-1\/Gly-GlyRalpha dynamic balance module of cerebral ischemia. Pharmacol Res. 2018;135:80\u20138.","journal-title":"Pharmacol Res"},{"issue":"2","key":"521_CR11","doi-asserted-by":"publisher","first-page":"110","DOI":"10.3724\/SP.J.1009.2013.00110","volume":"11","author":"S Li","year":"2013","unstructured":"Li S, Zhang B. Traditional chinese medicine network pharmacology: theory, methodology and application. Chin J Nat Med. 2013;11(2):110\u201320.","journal-title":"Chin J Nat Med"},{"key":"521_CR12","doi-asserted-by":"publisher","first-page":"104759","DOI":"10.1016\/j.phrs.2020.104759","volume":"156","author":"Z Ding","year":"2020","unstructured":"Ding Z, Zhong R, Yang Y, Xia T, Wang W, Wang Y, et al. Systems pharmacology reveals the mechanism of activity of ge-gen-qin-lian decoction against lps-induced acute lung injury: a novel strategy for exploring active components and effective mechanism of tcm formulae. Pharmacol Res. 2020;156:104759.","journal-title":"Pharmacol Res."},{"key":"521_CR13","doi-asserted-by":"publisher","first-page":"104365","DOI":"10.1016\/j.phrs.2019.104365","volume":"147","author":"J Zhao","year":"2019","unstructured":"Zhao J, Lv C, Wu Q, Zeng H, Guo X, Yang J, et al. Computational systems pharmacology reveals an antiplatelet and neuroprotective mechanism of deng-zhan-xi-xin injection in the treatment of ischemic stroke. Pharmacol Res. 2019;147:104365.","journal-title":"Pharmacol Res."},{"key":"521_CR14","unstructured":"Branch of Cardiovascular Disease, the Chinese Society of Traditional Chinese Medicine. Expert consensus for Chinese medicine diagnosis and treatment of stable angina pectoris of coronary heart disease. J Tradit Chin Med. 2018, 59 (5): 447\u2013450."},{"key":"521_CR15","unstructured":"SPCot P. Pharmacopoeia of the people\u2019s republic of china. Beijing: People\u2019s Medical Publishing House, 2005."},{"issue":"D1","key":"521_CR16","doi-asserted-by":"publisher","first-page":"D976","DOI":"10.1093\/nar\/gky987","volume":"47","author":"HY Xu","year":"2019","unstructured":"Xu HY, Zhang YQ, Liu ZM, Chen T, Lv CY, Tang SH, et al. Etcm: an encyclopaedia of traditional Chinese medicine. Nucleic Acids Res. 2019;47(D1):D976\u201382.","journal-title":"Nucleic Acids Res"},{"key":"521_CR17","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1758-2946-6-13","volume":"6","author":"J Ru","year":"2014","unstructured":"Ru J, Li P, Wang J, Zhou W, Li B, Huang C, et al. Tcmsp: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform. 2014;6:13.","journal-title":"J Cheminform"},{"issue":"D1","key":"521_CR18","doi-asserted-by":"publisher","first-page":"D1197","DOI":"10.1093\/nar\/gkaa1063","volume":"49","author":"S Fang","year":"2021","unstructured":"Fang S, Dong L, Liu L, Guo J, Zhao L, Zhang J, et al. Herb: a high-throughput experiment- and reference-guided database of traditional Chinese medicine. Nucleic Acids Res. 2021;49(D1):D1197\u2013206.","journal-title":"Nucleic Acids Res"},{"issue":"D1","key":"521_CR19","doi-asserted-by":"publisher","first-page":"D833","DOI":"10.1093\/nar\/gkw943","volume":"45","author":"J Pi\u00f1ero","year":"2017","unstructured":"Pi\u00f1ero J, Bravo \u00c0, Queralt-Rosinach N, Guti\u00e9rrez-Sacrist\u00e1n A, Deu-Pons J, Centeno E, et al. Disgenet: a comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res. 2017;45(D1):D833\u20139.","journal-title":"Nucleic Acids Res"},{"issue":"11","key":"521_CR20","doi-asserted-by":"publisher","first-page":"D1074","DOI":"10.1093\/nar\/gkx1037","volume":"46","author":"DS Wishart","year":"2018","unstructured":"Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, et al. Drugbank 5.0: a major update to the drugbank database for 2018. Nucleic Acids Res. 2018;46(11):D1074\u201382.","journal-title":"Nucleic Acids Res."},{"issue":"W1","key":"521_CR21","doi-asserted-by":"publisher","first-page":"W60","DOI":"10.1093\/nar\/gky311","volume":"46","author":"M Franz","year":"2018","unstructured":"Franz M, Rodriguez H, Lopes C, Zuberi K, Montojo J, Bader GD, et al. Genemania update 2018. Nucleic Acids Res. 2018;46(W1):W60\u20134.","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"521_CR22","doi-asserted-by":"publisher","first-page":"e86","DOI":"10.1002\/cpbi.86","volume":"68","author":"J Chong","year":"2019","unstructured":"Chong J, Wishart DS, Xia J. Using metaboanalyst 4.0 for comprehensive and integrative metabolomics data analysis. Curr Protoc Bioinform. 2019;68(1):e86.","journal-title":"Curr Protoc Bioinform"},{"issue":"11","key":"521_CR23","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498\u2013504.","journal-title":"Genome Res"},{"issue":"9","key":"521_CR24","doi-asserted-by":"publisher","first-page":"R183","DOI":"10.1186\/gb-2007-8-9-r183","volume":"8","author":"DW Huang","year":"2007","unstructured":"Huang DW, Sherman BT, Tan Q, Collins JR, Alvord WG, Roayaei J, et al. The David gene functional classification tool: a novel biological module-centric algorithm to functionally analyze large gene lists. Genome Biol. 2007;8(9):R183.","journal-title":"Genome Biol"},{"issue":"D1","key":"521_CR25","doi-asserted-by":"publisher","first-page":"D607","DOI":"10.1093\/nar\/gky1131","volume":"47","author":"D Szklarczyk","year":"2019","unstructured":"Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, et al. String v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47(D1):D607\u201313.","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"521_CR26","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","volume":"28","author":"M Kanehisa","year":"2000","unstructured":"Kanehisa M, Goto S. Kegg: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000;28(1):27\u201330.","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"521_CR27","doi-asserted-by":"publisher","first-page":"e8124","DOI":"10.15252\/msb.20178124","volume":"14","author":"R Argelaguet","year":"2018","unstructured":"Argelaguet R, Velten B, Arnol D, Dietrich S, Zenz T, Marioni JC, et al. Multi-omics factor analysis-a framework for unsupervised integration of multi-omics data sets. Mol Syst Biol. 2018;14(6):e8124.","journal-title":"Mol Syst Biol."},{"key":"521_CR28","first-page":"19","volume":"20","author":"M Olivier","year":"2019","unstructured":"Olivier M, Asmis R, Hawkins GA, Howard TD, Cox LA. The need for multi-omics biomarker signatures in precision medicine. Int J Mol Sci. 2019;20:19.","journal-title":"Int J Mol Sci"},{"issue":"Suppl 3","key":"521_CR29","first-page":"43","volume":"94","author":"P Mathes","year":"2005","unstructured":"Mathes P, Thiery J. The role of lipid metabolism in the prevention of coronary heart disease. Z Kardiol. 2005;94(Suppl 3):43\u201355.","journal-title":"Z Kardiol."},{"issue":"6","key":"521_CR30","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1089\/ars.2008.2280","volume":"11","author":"M Hamblin","year":"2009","unstructured":"Hamblin M, Chang L, Fan Y, Zhang J, Chen YE. Ppars and the cardiovascular system. Antioxid Redox Signal. 2009;11(6):1415\u201352.","journal-title":"Antioxid Redox Signal"},{"key":"521_CR31","doi-asserted-by":"publisher","first-page":"513","DOI":"10.3389\/fneur.2019.00513","volume":"10","author":"Z Bagoly","year":"2019","unstructured":"Bagoly Z, Szegedi I, K\u00e1lm\u00e1ndi R, T\u00f3th NK, Csiba L. Markers of coagulation and fibrinolysis predicting the outcome of acute ischemic stroke thrombolysis treatment: a review of the literature. Front Neurol. 2019;10:513.","journal-title":"Front Neurol"},{"issue":"4","key":"521_CR32","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1016\/S0950-351X(05)80083-7","volume":"4","author":"TA Sanders","year":"1990","unstructured":"Sanders TA. Polyunsaturated fatty acids and coronary heart disease. Baillieres Clin Endocrinol Metab. 1990;4(4):877\u201394.","journal-title":"Baillieres Clin Endocrinol Metab"},{"key":"521_CR33","doi-asserted-by":"publisher","first-page":"3","DOI":"10.5041\/RMMJ.10337","volume":"9","author":"C Grajeda-Iglesias","year":"2018","unstructured":"Grajeda-Iglesias C, Aviram M. Specific amino acids affect cardiovascular diseases and atherogenesis via protection against macrophage foam cell formation: review article. Rambam Maimonides Med J. 2018;9:3.","journal-title":"Rambam Maimonides Med J"},{"key":"521_CR34","first-page":"9","volume":"105","author":"G Biesenbach","year":"1989","unstructured":"Biesenbach G. Disorders of lipid metabolism in diabetes mellitus. Wien Med Wochenschr Suppl. 1989;105:9\u201317.","journal-title":"Wien Med Wochenschr Suppl"},{"issue":"10","key":"521_CR35","doi-asserted-by":"publisher","first-page":"101566","DOI":"10.1016\/j.isci.2020.101566","volume":"23","author":"SR Khan","year":"2020","unstructured":"Khan SR, Manialawy Y, Obersterescu A, Cox BJ, Gunderson EP, Wheeler MB. Diminished sphingolipid metabolism, a hallmark of future type 2 diabetes pathogenesis, is linked to pancreatic \u03b2 cell dysfunction. iScience. 2020;23(10):101566.","journal-title":"iScience."},{"issue":"2","key":"521_CR36","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.arcmed.2019.05.006","volume":"50","author":"Y L\u00f3pez-Hern\u00e1ndez","year":"2019","unstructured":"L\u00f3pez-Hern\u00e1ndez Y, Lara-Ram\u00edrez EE, Salgado-Bustamante M, L\u00f3pez JA, Oropeza-Valdez JJ, Jaime-S\u00e1nchez E, et al. Glycerophospholipid metabolism alterations in patients with type 2 diabetes mellitus and tuberculosis comorbidity. Arch Med Res. 2019;50(2):71\u20138.","journal-title":"Arch Med Res"},{"issue":"4","key":"521_CR37","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1083\/jcb.201810097","volume":"218","author":"YJ Park","year":"2019","unstructured":"Park YJ, Woo M. Pancreatic \u03b2 cells: gatekeepers of type 2 diabetes. J Cell Biol. 2019;218(4):1094\u20135.","journal-title":"J Cell Biol"},{"issue":"4","key":"521_CR38","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1042\/BST20140156","volume":"42","author":"S Jackowski","year":"2014","unstructured":"Jackowski S, Leonardi R. Deregulated coenzyme a, loss of metabolic flexibility and diabetes. Biochem Soc Trans. 2014;42(4):1118\u201322.","journal-title":"Biochem Soc Trans"},{"key":"521_CR39","doi-asserted-by":"publisher","first-page":"51","DOI":"10.3389\/fncel.2020.00051","volume":"14","author":"D Belov Kirdajova","year":"2020","unstructured":"Belov Kirdajova D, Kriska J, Tureckova J, Anderova M. Ischemia-triggered glutamate excitotoxicity from the perspective of glial cells. Fron Cell Neurosci. 2020;14:51.","journal-title":"Fron Cell Neurosci"},{"issue":"4","key":"521_CR40","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1161\/01.ATV.21.4.542","volume":"21","author":"ST Reddy","year":"2001","unstructured":"Reddy ST, Wadleigh DJ, Grijalva V, Ng C, Hama S, Gangopadhyay A, et al. Human paraoxonase-3 is an hdl-associated enzyme with biological activity similar to paraoxonase-1 protein but is not regulated by oxidized lipids. Arterioscler Thromb Vasc Biol. 2001;21(4):542\u20137.","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"1","key":"521_CR41","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.gene.2015.04.088","volume":"567","author":"M Mackness","year":"2015","unstructured":"Mackness M, Mackness B. Human paraoxonase-1 (pon1): Gene structure and expression, promiscuous activities and multiple physiological roles. Gene. 2015;567(1):12\u201321.","journal-title":"Gene"},{"issue":"3","key":"521_CR42","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1161\/01.ATV.0000060462.35946.B3","volume":"23","author":"O Rozenberg","year":"2003","unstructured":"Rozenberg O, Shih DM, Aviram M. Human serum paraoxonase 1 decreases macrophage cholesterol biosynthesis: Possible role for its phospholipase-a2-like activity and lysophosphatidylcholine formation. Arterioscler Thromb Vasc Biol. 2003;23(3):461\u20137.","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"16","key":"521_CR43","doi-asserted-by":"publisher","first-page":"4049","DOI":"10.3390\/ijms20164049","volume":"20","author":"MJ Meneses","year":"2019","unstructured":"Meneses MJ, Silvestre R, Sousa-Lima I, Macedo MP. Paraoxonase-1 as a regulator of glucose and lipid homeostasis: Impact on the onset and progression of metabolic disorders. Int J Mol Sci. 2019;20(16):4049.","journal-title":"Int J Mol Sci"},{"issue":"1","key":"521_CR44","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.atherosclerosis.2013.03.028","volume":"229","author":"M Koren-Gluzer","year":"2013","unstructured":"Koren-Gluzer M, Aviram M, Hayek T. Paraoxonase1 (pon1) reduces insulin resistance in mice fed a high-fat diet, and promotes glut4 overexpression in myocytes, via the irs-1\/akt pathway. Atherosclerosis. 2013;229(1):71\u20138.","journal-title":"Atherosclerosis"},{"issue":"6","key":"521_CR45","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1161\/ATVBAHA.110.216804","volume":"31","author":"M Ding","year":"2011","unstructured":"Ding M, Xie Y, Wagner RJ, Jin Y, Carrao AC, Liu LS, et al. Adiponectin induces vascular smooth muscle cell differentiation via repression of mammalian target of rapamycin complex 1 and foxo4. Arterioscler Thromb Vasc Biol. 2011;31(6):1403\u201310.","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"9","key":"521_CR46","doi-asserted-by":"publisher","first-page":"6153","DOI":"10.1074\/jbc.M109.088708","volume":"285","author":"K Ohashi","year":"2010","unstructured":"Ohashi K, Parker JL, Ouchi N, Higuchi A, Vita JA, Gokce N, et al. Adiponectin promotes macrophage polarization toward an anti-inflammatory phenotype. J Biol Chem. 2010;285(9):6153\u201360.","journal-title":"J Biol Chem"},{"key":"521_CR47","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/1475-2840-10-14","volume":"10","author":"A Kollias","year":"2011","unstructured":"Kollias A, Tsiotra PC, Ikonomidis I, Maratou E, Mitrou P, Kyriazi E, et al. Adiponectin levels and expression of adiponectin receptors in isolated monocytes from overweight patients with coronary artery disease. Cardiovasc Diabetol. 2011;10:14.","journal-title":"Cardiovasc Diabetol"},{"issue":"2","key":"521_CR48","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.cmet.2013.01.001","volume":"17","author":"T Yamauchi","year":"2013","unstructured":"Yamauchi T, Kadowaki T. Adiponectin receptor as a key player in healthy longevity and obesity-related diseases. Cell Metab. 2013;17(2):185\u201396.","journal-title":"Cell Metab"},{"issue":"2","key":"521_CR49","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1001\/jama.2009.976","volume":"302","author":"S Li","year":"2009","unstructured":"Li S, Shin HJ, Ding EL, van Dam RM. Adiponectin levels and risk of type 2 diabetes: A systematic review and meta-analysis. JAMA. 2009;302(2):179\u201388.","journal-title":"JAMA"},{"issue":"1","key":"521_CR50","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1073\/pnas.82.1.203","volume":"82","author":"NA Elshourbagy","year":"1985","unstructured":"Elshourbagy NA, Liao WS, Mahley RW, Taylor JM. Apolipoprotein e mrna is abundant in the brain and adrenals, as well as in the liver, and is present in other peripheral tissues of rats and marmosets. Proc Natl Acad Sci USA. 1985;82(1):203\u20137.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"2","key":"521_CR51","doi-asserted-by":"publisher","first-page":"30","DOI":"10.3390\/jcdd5020030","volume":"5","author":"L Bouchareychas","year":"2018","unstructured":"Bouchareychas L, Raffai RL. Apolipoprotein e and atherosclerosis: from lipoprotein metabolism to microrna control of inflammation. J Cardiovasc Dev Dis. 2018;5(2):30.","journal-title":"J Cardiovasc Dev Dis"},{"issue":"1","key":"521_CR52","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/ng0996-55","volume":"14","author":"M Miyata","year":"1996","unstructured":"Miyata M, Smith JD. Apolipoprotein e allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides. Nat Genet. 1996;14(1):55\u201361.","journal-title":"Nat Genet"},{"issue":"27","key":"521_CR53","doi-asserted-by":"publisher","first-page":"25043","DOI":"10.1074\/jbc.M102357200","volume":"276","author":"DK Swertfeger","year":"2001","unstructured":"Swertfeger DK, Hui DY. Apolipoprotein e receptor binding versus heparan sulfate proteoglycan binding in its regulation of smooth muscle cell migration and proliferation. J Biol Chem. 2001;276(27):25043\u20138.","journal-title":"J Biol Chem"},{"issue":"1","key":"521_CR54","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1074\/jbc.272.1.89","volume":"272","author":"DR Riddell","year":"1997","unstructured":"Riddell DR, Graham A, Owen JS. Apolipoprotein e inhibits platelet aggregation through the l-arginine: nitric oxide pathway. Implications for vascular disease. J Biol Chem. 1997;272(1):89\u201395.","journal-title":"J Biol Chem."},{"issue":"10","key":"521_CR55","doi-asserted-by":"publisher","first-page":"6366","DOI":"10.4049\/jimmunol.173.10.6366","volume":"173","author":"DJ Grainger","year":"2004","unstructured":"Grainger DJ, Reckless J, McKilligin E. Apolipoprotein e modulates clearance of apoptotic bodies in vitro and in vivo, resulting in a systemic proinflammatory state in apolipoprotein e-deficient mice. J Immunol. 2004;173(10):6366\u201375.","journal-title":"J Immunol"},{"issue":"10","key":"521_CR56","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1097\/00004647-200110000-00008","volume":"21","author":"K Kitagawa","year":"2001","unstructured":"Kitagawa K, Matsumoto M, Kuwabara K, Ohtsuki T, Hori M. Delayed, but marked, expression of apolipoprotein e is involved in tissue clearance after cerebral infarction. J Cereb Blood Flow Metab. 2001;21(10):1199\u2013207.","journal-title":"J Cereb Blood Flow Metab"},{"issue":"5","key":"521_CR57","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/0009-9120(92)80004-Z","volume":"25","author":"JM Kuyl","year":"1992","unstructured":"Kuyl JM, Mendelsohn D. Observed relationship between ratios HDL-cholesterol\/total cholesterol and apolipoprotein A1\/apolipoprotein B. Clin Biochem. 1992;25(5):313\u20136.","journal-title":"Clin Biochem"},{"issue":"5\u20136","key":"521_CR58","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1159\/000091537","volume":"21","author":"M Bhatia","year":"2006","unstructured":"Bhatia M, Howard SC, Clark TG, Neale R, Qizilbash N, Murphy MF, et al. Apolipoproteins as predictors of ischaemic stroke in patients with a previous transient ischaemic attack. Cerebrovasc Dis. 2006;21(5\u20136):323\u20138.","journal-title":"Cerebrovasc Dis"}],"container-title":["Chinese Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13020-021-00521-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13020-021-00521-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13020-021-00521-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T21:04:29Z","timestamp":1726002269000},"score":1,"resource":{"primary":{"URL":"https:\/\/cmjournal.biomedcentral.com\/articles\/10.1186\/s13020-021-00521-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,26]]},"references-count":58,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["521"],"URL":"https:\/\/doi.org\/10.1186\/s13020-021-00521-3","relation":{},"ISSN":["1749-8546"],"issn-type":[{"value":"1749-8546","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,26]]},"assertion":[{"value":"27 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The protocol and informed consent were reviewed and approved by the Beijing University of Chinese Medicine Clinical Trials and Biomedical Ethics Committee (No. DZMEC-KY-2019\u2013121).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publication"}},{"value":"The authors declare that they have no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"109"}}