{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T21:42:30Z","timestamp":1793396550889,"version":"4.5.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T00:00:00Z","timestamp":1611619200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T00:00:00Z","timestamp":1611619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Endocr Disord"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The present study aimed to evaluate the effect of artesunate (ART) on the reduction of cardiovascular complications in a type 1 diabetes model and to investigate the associated mechanism based on the receptor for advanced glycation end-product (RAGE)\/NF-\u03baB signaling pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 40 male Sprague-Dawley rats were randomly divided into five groups: The healthy, diabetic, 50\u2009mg\/kg ART (ig) treatment diabetic, 100\u2009mg\/kg ART (ig) treatment diabetic, and 6\u2009U\/kg insulin (iH) treatment diabetic groups. The treatment lasted 4\u2009weeks after the diabetic model was established via intraperitoneal injection of streptozotocin. Blood samples were collected, and cardiovascular tissues were harvested and processed to measure various parameters after the animals were sacrificed. The myocardium and aortic arch tissues were evaluated using hematoxylin-eosin and Masson staining. Expression levels of RAGE, NF-\u03baB, matrix metalloproteinase MMP9, MMP1 and CD68 in the myocardium and aortic arch tissues were detected using immunohistochemistry, and mRNA expression was determined using reverse transcription-quantitative PCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results of the present study demonstrated that ART treatment may restrain diabetes-induced cardiovascular complications by maintaining heart and body weight while reducing blood glucose, as well as regulating blood lipid indicators to normal level (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). The expression levels of NF-\u03baB, CD68, MMP1, MMP9 and RAGE were decreased in the ART-treated diabetic rats (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>ART treatment may have a protective role against diabetes-associated cardiovascular complications in diabetic rats by inhibiting the expression of proteins in the RAGE\/NF-\u03baB signaling pathway and downstream inflammatory factors. High concentrations of ART had a hypoglycemic effect, while a low concentration of ART prevented cardiovascular complications.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12902-021-00682-0","type":"journal-article","created":{"date-parts":[[2021,1,26]],"date-time":"2021-01-26T11:03:33Z","timestamp":1611659013000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Role of Artesunate on cardiovascular complications in rats with type 1 diabetes mellitus"],"prefix":"10.1186","volume":"21","author":[{"given":"Yi","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8900-9057","authenticated-orcid":false,"given":"Xiaolin","family":"Nong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaquan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingge","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiying","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,26]]},"reference":[{"issue":"1","key":"682_CR1","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/s40200-019-00403-4","volume":"18","author":"C Choubaya","year":"2019","unstructured":"Choubaya C, Chahine R, Zalloua P, Salameh Z. Periodontitis and diabetes interrelationships in rats: biochemical and histopathological variables. J Diabetes Metab Disord. 2019;18(1):163\u201372.","journal-title":"J Diabetes Metab Disord"},{"issue":"1","key":"682_CR2","doi-asserted-by":"publisher","first-page":"329","DOI":"10.2337\/diacare.16.1.329","volume":"16","author":"H Loe","year":"1993","unstructured":"Loe H. Periodontal disease. The sixth complication of diabetes mellitus. Diabetes Care. 1993;16(1):329\u201334.","journal-title":"Diabetes Care"},{"issue":"4","key":"682_CR3","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1016\/S0002-9440(10)63909-0","volume":"162","author":"TM Wendt","year":"2003","unstructured":"Wendt TM, Tanji N, Guo J, Kislinger TR, Qu W, Lu Y, et al. RAGE drives the development of glomerulosclerosis and implicates podocyte activation in the pathogenesis of diabetic nephropathy. Am J Pathol. 2003;162(4):1123\u201337.","journal-title":"Am J Pathol"},{"issue":"2","key":"682_CR4","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1021\/pr800858h","volume":"8","author":"Q Zhang","year":"2009","unstructured":"Zhang Q, Ames JM, Smith RD, Baynes JW, Metz TO. A perspective on the Maillard reaction and the analysis of protein glycation by mass spectrometry: probing the pathogenesis of chronic disease. J Proteome Res. 2009;8(2):754\u201369.","journal-title":"J Proteome Res"},{"issue":"6","key":"682_CR5","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1016\/j.yjmcc.2011.08.001","volume":"51","author":"M Lenski","year":"2011","unstructured":"Lenski M, Kazakov A, Marx N, Bohm M, Laufs U. Effects of DPP-4 inhibition on cardiac metabolism and function in mice. J Mol Cell Cardiol. 2011;51(6):906\u201318.","journal-title":"J Mol Cell Cardiol"},{"issue":"11","key":"682_CR6","doi-asserted-by":"publisher","first-page":"2185","DOI":"10.1016\/j.cellsig.2013.06.013","volume":"25","author":"J Xie","year":"2013","unstructured":"Xie J, Mendez JD, Mendez-Valenzuela V, Aguilar-Hernandez MM. Cellular signalling of the receptor for advanced glycation end products (RAGE). Cell Signal. 2013;25(11):2185\u201397.","journal-title":"Cell Signal"},{"issue":"3","key":"682_CR7","doi-asserted-by":"publisher","first-page":"292","DOI":"10.4103\/0972-124X.115642","volume":"17","author":"HS Grover","year":"2013","unstructured":"Grover HS, Luthra S. Molecular mechanisms involved in the bidirectional relationship between diabetes mellitus and periodontal disease. J Indian Soc Periodontol. 2013;17(3):292\u2013301.","journal-title":"J Indian Soc Periodontol"},{"issue":"2","key":"682_CR8","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/ijos.2015.2","volume":"7","author":"YY Wu","year":"2015","unstructured":"Wu YY, Xiao E, Graves DT. Diabetes mellitus related bone metabolism and periodontal disease. Int J Oral Sci. 2015;7(2):63\u201372.","journal-title":"Int J Oral Sci"},{"issue":"1","key":"682_CR9","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s11882-011-0236-1","volume":"12","author":"M Frieri","year":"2012","unstructured":"Frieri M. Accelerated atherosclerosis in systemic lupus erythematosus: role of proinflammatory cytokines and therapeutic approaches. Curr Allergy Asthma Rep. 2012;12(1):25\u201332.","journal-title":"Curr Allergy Asthma Rep"},{"issue":"Suppl 1","key":"682_CR10","doi-asserted-by":"publisher","first-page":"S43","DOI":"10.1160\/THS10-11-0739","volume":"105","author":"K Hess","year":"2011","unstructured":"Hess K, Grant PJ. Inflammation and thrombosis in diabetes. Thromb Haemost. 2011;105(Suppl 1):S43\u201354.","journal-title":"Thromb Haemost"},{"issue":"2","key":"682_CR11","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.pharmthera.2012.08.002","volume":"136","author":"M Kaplan","year":"2012","unstructured":"Kaplan M, Aviram M, Hayek T. Oxidative stress and macrophage foam cell formation during diabetes mellitus-induced atherogenesis: role of insulin therapy. Pharmacol Ther. 2012;136(2):175\u201385.","journal-title":"Pharmacol Ther"},{"issue":"2","key":"682_CR12","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1093\/cvr\/cvu115","volume":"103","author":"S Martinez-Hervas","year":"2014","unstructured":"Martinez-Hervas S, Vinue A, Nunez L, Andres-Blasco I, Piqueras L, Real JT, et al. Insulin resistance aggravates atherosclerosis by reducing vascular smooth muscle cell survival and increasing CX3CL1\/CX3CR1 axis. Cardiovasc Res. 2014;103(2):324\u201336.","journal-title":"Cardiovasc Res"},{"key":"682_CR13","doi-asserted-by":"publisher","first-page":"917631","DOI":"10.1155\/2014\/917631","volume":"2014","author":"A Monea","year":"2014","unstructured":"Monea A, Mezei T, Popsor S, Monea M. Oxidative stress: a link between diabetes mellitus and periodontal disease. Int J Endocrinol. 2014;2014:917631.","journal-title":"Int J Endocrinol"},{"issue":"1","key":"682_CR14","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1007\/s11892-004-0008-6","volume":"4","author":"M Peppa","year":"2004","unstructured":"Peppa M, Uribarri J, Vlassara H. The role of advanced glycation end products in the development of atherosclerosis. Curr Diab Rep. 2004;4(1):31\u20136.","journal-title":"Curr Diab Rep"},{"issue":"5","key":"682_CR15","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1161\/CIRCRESAHA.109.212217","volume":"106","author":"SF Yan","year":"2010","unstructured":"Yan SF, Ramasamy R, Schmidt AM. The RAGE axis: a fundamental mechanism signaling danger to the vulnerable vasculature. Circ Res. 2010;106(5):842\u201353.","journal-title":"Circ Res"},{"key":"682_CR16","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1146\/annurev-med-041316-085215","volume":"69","author":"BI Hudson","year":"2018","unstructured":"Hudson BI, Lippman ME. Targeting RAGE signaling in inflammatory disease. Annu Rev Med. 2018;69:349\u201364.","journal-title":"Annu Rev Med"},{"issue":"1","key":"682_CR17","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1189\/jlb.0904498","volume":"78","author":"Y Lu","year":"2005","unstructured":"Lu Y, Wahl LM. Production of matrix metalloproteinase-9 by activated human monocytes involves a phosphatidylinositol-3 kinase\/Akt\/IKKalpha\/NF-kappaB pathway. J Leukoc Biol. 2005;78(1):259\u201365.","journal-title":"J Leukoc Biol"},{"issue":"14","key":"682_CR18","doi-asserted-by":"publisher","first-page":"2395","DOI":"10.2174\/13816128113199990475","volume":"20","author":"K Fukami","year":"2014","unstructured":"Fukami K, Yamagishi S, Okuda S. Role of AGEs-RAGE system in cardiovascular disease. Curr Pharm Des. 2014;20(14):2395\u2013402.","journal-title":"Curr Pharm Des"},{"key":"682_CR19","doi-asserted-by":"publisher","first-page":"6809703","DOI":"10.1155\/2016\/6809703","volume":"2016","author":"AM Kay","year":"2016","unstructured":"Kay AM, Simpson CL, Stewart JA Jr. The role of AGE\/RAGE signaling in diabetes-mediated vascular calcification. J Diabetes Res. 2016;2016:6809703.","journal-title":"J Diabetes Res"},{"key":"682_CR20","doi-asserted-by":"crossref","unstructured":"Borriello M, Iannuzzi C, Sirangelo I. Pinocembrin Protects from AGE-Induced Cytotoxicity and Inhibits Non-Enzymatic Glycation in Human Insulin. Cell. 2019;8(5):385.","DOI":"10.3390\/cells8050385"},{"issue":"46","key":"682_CR21","doi-asserted-by":"publisher","first-page":"3423","DOI":"10.1093\/eurheartj\/ehx510","volume":"38","author":"G LaRocca","year":"2017","unstructured":"LaRocca G, Aspelund T, Greve AM, Eiriksdottir G, Acharya T, Thorgeirsson G, et al. Fibrosis as measured by the biomarker, tissue inhibitor metalloproteinase-1, predicts mortality in age gene environment susceptibility-Reykjavik (AGES-Reykjavik) study. Eur Heart J. 2017;38(46):3423\u201330.","journal-title":"Eur Heart J"},{"key":"682_CR22","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.carpath.2017.05.003","volume":"29","author":"FS Silva","year":"2017","unstructured":"Silva FS, Bortolin RH, Araujo DN, Marques DES, Lima J, Rezende AA, et al. Exercise training ameliorates matrix metalloproteinases 2 and 9 messenger RNA expression and mitigates adverse left ventricular remodeling in streptozotocin-induced diabetic rats. Cardiovasc Pathol. 2017;29:37\u201344.","journal-title":"Cardiovasc Pathol"},{"issue":"9","key":"682_CR23","doi-asserted-by":"publisher","first-page":"4366","DOI":"10.1111\/jcmm.13728","volume":"22","author":"RD Macarie","year":"2018","unstructured":"Macarie RD, Vadana M, Ciortan L, Tucureanu MM, Ciobanu A, Vinereanu D, et al. The expression of MMP-1 and MMP-9 is up-regulated by smooth muscle cells after their cross-talk with macrophages in high glucose conditions. J Cell Mol Med. 2018;22(9):4366\u201376.","journal-title":"J Cell Mol Med"},{"issue":"2","key":"682_CR24","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1093\/cvr\/cvy226","volume":"115","author":"V Malek","year":"2019","unstructured":"Malek V, Gaikwad AB. Telmisartan and thiorphan combination treatment attenuates fibrosis and apoptosis in preventing diabetic cardiomyopathy. Cardiovasc Res. 2019;115(2):373\u201384.","journal-title":"Cardiovasc Res"},{"issue":"10","key":"682_CR25","doi-asserted-by":"publisher","first-page":"e0164838","DOI":"10.1371\/journal.pone.0164838","volume":"11","author":"L Zhang","year":"2016","unstructured":"Zhang L, Qian H, Sha M, Luan Z, Lin M, Yuan D, et al. Downregulation of HOTAIR expression mediated anti-metastatic effect of Artesunate on cervical Cancer by inhibiting COX-2 expression. PLoS One. 2016;11(10):e0164838.","journal-title":"PLoS One"},{"key":"682_CR26","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.micpath.2018.03.014","volume":"118","author":"L Lin","year":"2018","unstructured":"Lin L, Mao X, Sun Y, Cui H. Antibacterial mechanism of artemisinin \/ beta-cyclodextrins against methicillin-resistant Staphylococcus aureus (MRSA). Microb Pathog. 2018;118:66\u201373.","journal-title":"Microb Pathog"},{"issue":"8","key":"682_CR27","doi-asserted-by":"publisher","first-page":"e104762","DOI":"10.1371\/journal.pone.0104762","volume":"9","author":"L Hou","year":"2014","unstructured":"Hou L, Block KE, Huang H. Artesunate abolishes germinal center B cells and inhibits autoimmune arthritis. PLoS One. 2014;9(8):e104762.","journal-title":"PLoS One"},{"issue":"1","key":"682_CR28","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13020-019-0228-y","volume":"14","author":"W Wang","year":"2016","unstructured":"Wang W, Liang YS. Artemisinin: a wonder drug from Chinese natural medicines. Chin J Nat Med. 2016;14(1):5\u20136.","journal-title":"Chin J Nat Med"},{"issue":"1","key":"682_CR29","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s40618-015-0328-1","volume":"39","author":"L Yu","year":"2016","unstructured":"Yu L, Chen JF, Shuai X, Xu Y, Ding Y, Zhang J, et al. Artesunate protects pancreatic beta cells against cytokine-induced damage via SIRT1 inhibiting NF-kappaB activation. J Endocrinol Investig. 2016;39(1):83\u201391.","journal-title":"J Endocrinol Investig"},{"issue":"7","key":"682_CR30","doi-asserted-by":"publisher","first-page":"8241","DOI":"10.1096\/fj.201900146R","volume":"33","author":"Z Li","year":"2019","unstructured":"Li Z, Shi X, Liu J, Shao F, Huang G, Zhou Z, et al. Artesunate prevents type 1 diabetes in NOD mice mainly by inducing protective IL-4-producing T cells and regulatory T cells. FASEB J. 2019;33(7):8241\u20138.","journal-title":"FASEB J"},{"issue":"2","key":"682_CR31","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1038\/s41401-019-0289-6","volume":"41","author":"XZ Zeng","year":"2020","unstructured":"Zeng XZ, Zhang YY, Yang Q, Wang S, Zou BH, Tan YH, et al. Artesunate attenuates LPS-induced osteoclastogenesis by suppressing TLR4\/TRAF6 and PLCgamma1-Ca(2+)-NFATc1 signaling pathway. Acta Pharmacol Sin. 2020;41(2):229\u201336.","journal-title":"Acta Pharmacol Sin"},{"issue":"2","key":"682_CR32","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1002\/jcp.27070","volume":"234","author":"G Zuo","year":"2019","unstructured":"Zuo G, Ren X, Qian X, Ye P, Luo J, Gao X, et al. Inhibition of JNK and p38 MAPK-mediated inflammation and apoptosis by ivabradine improves cardiac function in streptozotocin-induced diabetic cardiomyopathy. J Cell Physiol. 2019;234(2):1925\u201336.","journal-title":"J Cell Physiol"},{"key":"682_CR33","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.cbi.2018.07.011","volume":"293","author":"Z Sun","year":"2018","unstructured":"Sun Z, Ma Y, Chen F, Wang S, Chen B, Shi J. Artesunate ameliorates high glucose-induced rat glomerular mesangial cell injury by suppressing the TLR4\/NF-kappaB\/NLRP3 inflammasome pathway. Chem Biol Interact. 2018;293:11\u20139.","journal-title":"Chem Biol Interact"},{"key":"682_CR34","doi-asserted-by":"crossref","unstructured":"Sun X, Yan P, Zou C, Wong YK, Shu Y, Lee YM, et al. Targeting autophagy enhances the anticancer effect of artemisinin and its derivatives. Med Res Rev. 2019;39(6):2172\u201393.","DOI":"10.1002\/med.21580"},{"key":"682_CR35","doi-asserted-by":"crossref","unstructured":"Nong X, Rajbanshi G, Chen L, Li J, Li Z, Liu T, et al. Effect of artesunate and relation with TGF-beta1 and SMAD3 signaling on experimental hypertrophic scar model in rabbit ear. Arch Dermatol Res. 2019;311(10):761\u201372.","DOI":"10.1007\/s00403-019-01960-7"},{"key":"682_CR36","doi-asserted-by":"publisher","first-page":"152968","DOI":"10.1016\/j.phymed.2019.152968","volume":"63","author":"T Su","year":"2019","unstructured":"Su T, Li F, Guan J, Liu L, Huang P, Wang Y, et al. Artemisinin and its derivatives prevent helicobacter pylori-induced gastric carcinogenesis via inhibition of NF-kappaB signaling. Phytomedicine. 2019;63:152968.","journal-title":"Phytomedicine."},{"issue":"Suppl C","key":"682_CR37","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1093\/eurheartj\/16.suppl_C.45","volume":"16","author":"CG Brilla","year":"1995","unstructured":"Brilla CG, Maisch B, Zhou G, Weber KT. Hormonal regulation of cardiac fibroblast function. Eur Heart J. 1995;16(Suppl C):45\u201350.","journal-title":"Eur Heart J"},{"issue":"4","key":"682_CR38","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1016\/j.yjmcc.2010.01.006","volume":"48","author":"M Wang","year":"2010","unstructured":"Wang M, Zhang J, Walker SJ, Dworakowski R, Lakatta EG, Shah AM. Involvement of NADPH oxidase in age-associated cardiac remodeling. J Mol Cell Cardiol. 2010;48(4):765\u201372.","journal-title":"J Mol Cell Cardiol"},{"issue":"8","key":"682_CR39","doi-asserted-by":"publisher","first-page":"e104255","DOI":"10.1371\/journal.pone.0104255","volume":"9","author":"C Li","year":"2014","unstructured":"Li C, Wang Y, Qiu Q, Shi T, Wu Y, Han J, et al. Qishenyiqi protects ligation-induced left ventricular remodeling by attenuating inflammation and fibrosis via STAT3 and NF-kappaB signaling pathway. PLoS One. 2014;9(8):e104255.","journal-title":"PLoS One"},{"issue":"2","key":"682_CR40","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.trstmh.2006.04.010","volume":"101","author":"Q Li","year":"2007","unstructured":"Li Q, Xie LH, Johnson TO, Si Y, Haeberle AS, Weina PJ. Toxicity evaluation of artesunate and artelinate in Plasmodium berghei-infected and uninfected rats. Trans R Soc Trop Med Hyg. 2007;101(2):104\u201312.","journal-title":"Trans R Soc Trop Med Hyg"}],"container-title":["BMC Endocrine Disorders"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12902-021-00682-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12902-021-00682-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12902-021-00682-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T05:38:38Z","timestamp":1697693918000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcendocrdisord.biomedcentral.com\/articles\/10.1186\/s12902-021-00682-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,26]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["682"],"URL":"https:\/\/doi.org\/10.1186\/s12902-021-00682-0","relation":{},"ISSN":["1472-6823"],"issn-type":[{"value":"1472-6823","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,26]]},"assertion":[{"value":"26 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 January 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The Animal Care and Welfare Committee for Scientific Research at Guangxi Medical University (Nanning, China) approved the experiments, which were performed in accordance with the guidelines of the National Institutes of Health (No.201802018).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare that there is no conflict of interest regarding the publication of this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"19"}}