{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T15:47:03Z","timestamp":1759333623623},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Gastroenterol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Although salt plays an important role in maintaining the normal physiological metabolism of the human body, many abnormalities in the liver caused by a high-salt diet, especially with normal pathological results, are not well characterized.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Eight-week-old female C57BL\/6 mice were randomly divided into a normal group and a high salt group. These groups were then fed with normal or sodium-rich chow (containing 6% NaCl) for 6\u00a0weeks. Liver injury was evaluated, and the influences of a high-salt diet on the liver were analyzed by transcriptome sequencing at the end of week 6.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We found that although no liver parenchymal injury could be found after high-salt feeding, many metabolic abnormalities had formed based on transcriptome sequencing results. GO and KEGG enrichment analyses of differentially expressed genes revealed that at least 15 enzymatic activities and the metabolism of multiple substances were affected by a high-salt diet. Moreover, a variety of signaling and metabolic pathways, as well as numerous biological functions, were involved in liver dysfunction due to a high-salt diet. This included some known pathways and many novel ones, such as retinol metabolism, linoleic acid metabolism, steroid hormone biosynthesis, and signaling pathways.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>A high-salt diet can induce serious abnormal liver metabolic activities in mice at the transcriptional level, although substantial physical damage may not yet be visible. This study, to our knowledge, was the first to reveal the impact of a high-salt diet on the liver at the omics level, and provides theoretical support for potential clinical risk evaluation, pathogenic mechanisms, and drug design for combating liver dysfunction. This study also provides a serious candidate direction for further research on the physiological impacts of high-salt diets.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12876-021-01912-4","type":"journal-article","created":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T08:02:46Z","timestamp":1630137766000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Transcriptome sequencing reveals high-salt diet-induced abnormal liver metabolic pathways in mice"],"prefix":"10.1186","volume":"21","author":[{"given":"Yanping","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yufei","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiufei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,8,28]]},"reference":[{"issue":"3","key":"1912_CR1","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1093\/ije\/dyp139","volume":"38","author":"IJ Brown","year":"2009","unstructured":"Brown IJ, Tzoulaki I, Candeias V, Elliott P. Salt intakes around the world: implications for public health. Int J Epidemiol. 2009;38(3):791\u2013813.","journal-title":"Int J Epidemiol"},{"issue":"1","key":"1912_CR2","doi-asserted-by":"publisher","first-page":"e010737","DOI":"10.1161\/JAHA.118.010737","volume":"8","author":"J Zhang","year":"2019","unstructured":"Zhang J, Guo X, Lu Z, Tang J, Li Y, Xu A, Liu S. Cardiovascular diseases deaths attributable to high sodium intake in Shandong Province, China. J Am Heart Assoc. 2019;8(1):e010737.","journal-title":"J Am Heart Assoc"},{"issue":"7","key":"1912_CR3","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1056\/NEJMoa0907355","volume":"362","author":"K Bibbins-Domingo","year":"2010","unstructured":"Bibbins-Domingo K, Chertow GM, Coxson PG, Moran A, Lightwood JM, Pletcher MJ, Goldman L. Projected effect of dietary salt reductions on future cardiovascular disease. N Engl J Med. 2010;362(7):590\u20139.","journal-title":"N Engl J Med"},{"issue":"6","key":"1912_CR4","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1161\/STROKEAHA.117.020277","volume":"49","author":"Y Li","year":"2018","unstructured":"Li Y, Huang Z, Jin C, Xing A, Liu Y, Huangfu C, Lichtenstein AH, Tucker KL, Wu S, Gao X. Longitudinal change of perceived salt intake and stroke risk in a Chinese population. Stroke. 2018;49(6):1332\u20139.","journal-title":"Stroke"},{"issue":"2","key":"1912_CR5","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1007\/s00125-003-1303-5","volume":"47","author":"M Vedovato","year":"2004","unstructured":"Vedovato M, Lepore G, Coracina A, Dodesini AR, Jori E, Tiengo A, Del Prato S, Trevisan R. Effect of sodium intake on blood pressure and albuminuria in Type 2 diabetic patients: the role of insulin resistance. Diabetologia. 2004;47(2):300\u20133.","journal-title":"Diabetologia"},{"issue":"7","key":"1912_CR6","doi-asserted-by":"publisher","first-page":"e69689","DOI":"10.1371\/journal.pone.0069689","volume":"8","author":"SC Larsen","year":"2013","unstructured":"Larsen SC, Angquist L, Sorensen TI, Heitmann BL. 24h urinary sodium excretion and subsequent change in weight, waist circumference and body composition. PLoS ONE. 2013;8(7):e69689.","journal-title":"PLoS ONE"},{"issue":"3","key":"1912_CR7","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1017\/S1368980011002138","volume":"15","author":"L Libuda","year":"2012","unstructured":"Libuda L, Kersting M, Alexy U. Consumption of dietary salt measured by urinary sodium excretion and its association with body weight status in healthy children and adolescents. Public Health Nutr. 2012;15(3):433\u201341.","journal-title":"Public Health Nutr"},{"issue":"7","key":"1912_CR8","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/j.metabol.2015.03.010","volume":"64","author":"JH Huh","year":"2015","unstructured":"Huh JH, Lim JS, Lee MY, Chung CH, Shin JY. Gender-specific association between urinary sodium excretion and body composition: analysis of the 2008\u20132010 Korean National Health and Nutrition Examination Surveys. Metab Clin Exp. 2015;64(7):837\u201344.","journal-title":"Metab Clin Exp"},{"issue":"536","key":"1912_CR9","doi-asserted-by":"publisher","first-page":"eaay3850","DOI":"10.1126\/scitranslmed.aay3850","volume":"12","author":"K Jobin","year":"2020","unstructured":"Jobin K, Stumpf NE, Schwab S, Eichler M, Neubert P, Rauh M, Adamowski M, Babyak O, Hinze D, Sivalingam S, et al. A high-salt diet compromises antibacterial neutrophil responses through hormonal perturbation. Sci Transl Med. 2020;12(536):eaay3850.","journal-title":"Sci Transl Med"},{"issue":"5","key":"1912_CR10","doi-asserted-by":"publisher","first-page":"1793","DOI":"10.1093\/ndt\/gfr600","volume":"27","author":"S Bernardi","year":"2012","unstructured":"Bernardi S, Toffoli B, Zennaro C, Tikellis C, Monticone S, Losurdo P, Bellini G, Thomas MC, Fallo F, Veglio F, et al. High-salt diet increases glomerular ACE\/ACE2 ratio leading to oxidative stress and kidney damage. Nephrol Dial Transplant. 2012;27(5):1793\u2013800.","journal-title":"Nephrol Dial Transplant"},{"issue":"11","key":"1912_CR11","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1038\/hr.2017.31","volume":"40","author":"H Takahashi","year":"2017","unstructured":"Takahashi H, Nakagawa S, Wu Y, Kawabata Y, Numabe A, Yanagi Y, Tamaki Y, Uehara Y, Araie M. A high-salt diet enhances leukocyte adhesion in association with kidney injury in young Dahl salt-sensitive rats. Hypertens Res. 2017;40(11):912\u201320.","journal-title":"Hypertens Res"},{"issue":"1","key":"1912_CR12","doi-asserted-by":"publisher","first-page":"F33","DOI":"10.1152\/ajprenal.00040.2014","volume":"307","author":"RC Fellner","year":"2014","unstructured":"Fellner RC, Cook AK, O\u2019Connor PM, Zhang S, Pollock DM, Inscho EW. High-salt diet blunts renal autoregulation by a reactive oxygen species-dependent mechanism. Am J Physiol Renal Physiol. 2014;307(1):F33-40.","journal-title":"Am J Physiol Renal Physiol"},{"issue":"41","key":"1912_CR13","doi-asserted-by":"publisher","first-page":"16281","DOI":"10.1073\/pnas.0707791104","volume":"104","author":"H Oberleithner","year":"2007","unstructured":"Oberleithner H, Riethmuller C, Schillers H, MacGregor GA, de Wardener HE, Hausberg M. Plasma sodium stiffens vascular endothelium and reduces nitric oxide release. Proc Natl Acad Sci USA. 2007;104(41):16281\u20136.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"12","key":"1912_CR14","first-page":"1230","volume":"1802","author":"OV Fedorova","year":"2010","unstructured":"Fedorova OV, Shapiro JI, Bagrov AY. Endogenous cardiotonic steroids and salt-sensitive hypertension. Biochem Biophys Acta. 2010;1802(12):1230\u20136.","journal-title":"Biochem Biophys Acta"},{"issue":"12","key":"1912_CR15","doi-asserted-by":"publisher","first-page":"3138","DOI":"10.1073\/pnas.1713837115","volume":"115","author":"MA Lanaspa","year":"2018","unstructured":"Lanaspa MA, Kuwabara M, Andres-Hernando A, Li N, Cicerchi C, Jensen T, Orlicky DJ, Roncal-Jimenez CA, Ishimoto T, Nakagawa T, et al. High salt intake causes leptin resistance and obesity in mice by stimulating endogenous fructose production and metabolism. Proc Natl Acad Sci USA. 2018;115(12):3138\u201343.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"7","key":"1912_CR16","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.1021\/acs.jafc.5b05897","volume":"64","author":"G Wang","year":"2016","unstructured":"Wang G, Yeung CK, Wong WY, Zhang N, Wei YF, Zhang JL, Yan Y, Wong CY, Tang JJ, Chuai M, et al. Liver fibrosis can be induced by high salt intake through excess reactive oxygen species (ROS) production. J Agric Food Chem. 2016;64(7):1610\u20137.","journal-title":"J Agric Food Chem"},{"issue":"6788","key":"1912_CR17","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1038\/35015701","volume":"405","author":"DJ Lockhart","year":"2000","unstructured":"Lockhart DJ, Winzeler EA. Genomics, gene expression and DNA arrays. Nature. 2000;405(6788):827\u201336.","journal-title":"Nature"},{"issue":"1","key":"1912_CR18","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/nrg2626","volume":"11","author":"ML Metzker","year":"2010","unstructured":"Metzker ML. Sequencing technologies\u2014the next generation. Nat Rev Genet. 2010;11(1):31\u201346.","journal-title":"Nat Rev Genet"},{"issue":"2","key":"1912_CR19","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/nrg2934","volume":"12","author":"F Ozsolak","year":"2011","unstructured":"Ozsolak F, Milos PM. RNA sequencing: advances, challenges and opportunities. Nat Rev Genet. 2011;12(2):87\u201398.","journal-title":"Nat Rev Genet"},{"issue":"5","key":"1912_CR20","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/nrg.2016.10","volume":"17","author":"SA Byron","year":"2016","unstructured":"Byron SA, Van Keuren-Jensen KR, Engelthaler DM, Carpten JD, Craig DW. Translating RNA sequencing into clinical diagnostics: opportunities and challenges. Nat Rev Genet. 2016;17(5):257\u201371.","journal-title":"Nat Rev Genet"},{"issue":"7","key":"1912_CR21","doi-asserted-by":"publisher","first-page":"e40092","DOI":"10.1371\/journal.pone.0040092","volume":"7","author":"D Sinicropi","year":"2012","unstructured":"Sinicropi D, Qu K, Collin F, Crager M, Liu ML, Pelham RJ, Pho M, Dei Rossi A, Jeong J, Scott A, et al. Whole transcriptome RNA-Seq analysis of breast cancer recurrence risk using formalin-fixed paraffin-embedded tumor tissue. PLoS ONE. 2012;7(7):e40092.","journal-title":"PLoS ONE"},{"key":"1912_CR22","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.meegid.2017.02.003","volume":"49","author":"LH Patino","year":"2017","unstructured":"Patino LH, Ramirez JD. RNA-seq in kinetoplastids: a powerful tool for the understanding of the biology and host-pathogen interactions. Infect Genet Evol. 2017;49:273\u201382.","journal-title":"Infect Genet Evol"},{"key":"1912_CR23","doi-asserted-by":"publisher","first-page":"491963","DOI":"10.1155\/2014\/491963","volume":"2014","author":"F Gao","year":"2014","unstructured":"Gao F, Liang Y, Wang X, Lu Z, Li L, Zhu S, Liu D, Yan Z, Zhu Z. TRPV1 activation attenuates high-salt diet-induced cardiac hypertrophy and fibrosis through PPAR-delta upregulation. PPAR Res. 2014;2014:491963.","journal-title":"PPAR Res"},{"issue":"2","key":"1912_CR24","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1515\/jbcpp-2017-0074","volume":"29","author":"E Ozurumba","year":"2018","unstructured":"Ozurumba E, Mathew O, Ranganna K, Choi M, Oyekan A. Regulation of hypoxia inducible factor\/prolyl hydroxylase binding domain proteins 1 by PPARalpha and high salt diet. J Basic Clin Physiol Pharmacol. 2018;29(2):165\u201373.","journal-title":"J Basic Clin Physiol Pharmacol"},{"issue":"1","key":"1912_CR25","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s40168-018-0433-4","volume":"6","author":"PM Miranda","year":"2018","unstructured":"Miranda PM, De Palma G, Serkis V, Lu J, Louis-Auguste MP, McCarville JL, Verdu EF, Collins SM, Bercik P. High salt diet exacerbates colitis in mice by decreasing Lactobacillus levels and butyrate production. Microbiome. 2018;6(1):57.","journal-title":"Microbiome"},{"issue":"1","key":"1912_CR26","first-page":"63","volume":"41","author":"P Fressinaud","year":"1980","unstructured":"Fressinaud P, Rohmer V, Galland F, Marcais J, Bigorne JC, Fressinaud L. Effects of low, normal and high sodium diet on antidiuretic hormone and prolactin (author\u2019s transl). Ann Endocrinol. 1980;41(1):63\u20134.","journal-title":"Ann Endocrinol"},{"issue":"11","key":"1912_CR27","doi-asserted-by":"publisher","first-page":"e0143222","DOI":"10.1371\/journal.pone.0143222","volume":"10","author":"JH Huh","year":"2015","unstructured":"Huh JH, Lee KJ, Lim JS, Lee MY, Park HJ, Kim MY, Kim JW, Chung CH, Shin JY, Kim HS, et al. High dietary sodium intake assessed by estimated 24-h urinary sodium excretion is associated with NAFLD and hepatic fibrosis. PLoS ONE. 2015;10(11):e0143222.","journal-title":"PLoS ONE"},{"issue":"6","key":"1912_CR28","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1111\/jhn.12674","volume":"32","author":"X Shen","year":"2019","unstructured":"Shen X, Jin C, Wu Y, Zhang Y, Wang X, Huang W, Li J, Wu S, Gao X. Prospective study of perceived dietary salt intake and the risk of non-alcoholic fatty liver disease. J Hum Nutr Diet. 2019;32(6):802\u20139.","journal-title":"J Hum Nutr Diet"},{"issue":"4","key":"1912_CR29","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1016\/S0016-5085(98)70599-2","volume":"114","author":"CP Day","year":"1998","unstructured":"Day CP, James OF. Steatohepatitis: a tale of two \u201chits\u201d? Gastroenterology. 1998;114(4):842\u20135.","journal-title":"Gastroenterology"},{"key":"1912_CR30","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.freeradbiomed.2015.12.016","volume":"91","author":"MA Abdelmegeed","year":"2016","unstructured":"Abdelmegeed MA, Choi Y, Ha SK, Song BJ. Cytochrome P450\u20132E1 promotes aging-related hepatic steatosis, apoptosis and fibrosis through increased nitroxidative stress. Free Radical Biol Med. 2016;91:188\u2013202.","journal-title":"Free Radical Biol Med"},{"issue":"3","key":"1912_CR31","doi-asserted-by":"publisher","first-page":"273","DOI":"10.2174\/1389200043335531","volume":"5","author":"JP Villeneuve","year":"2004","unstructured":"Villeneuve JP, Pichette V. Cytochrome P450 and liver diseases. Curr Drug Metab. 2004;5(3):273\u201382.","journal-title":"Curr Drug Metab"},{"issue":"1","key":"1912_CR32","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.taap.2011.08.011","volume":"257","author":"A Abu-Bakar","year":"2011","unstructured":"Abu-Bakar A, Arthur DM, Aganovic S, Ng JC, Lang MA. Inducible bilirubin oxidase: a novel function for the mouse cytochrome P450 2A5. Toxicol Appl Pharmacol. 2011;257(1):14\u201322.","journal-title":"Toxicol Appl Pharmacol"},{"issue":"10","key":"1912_CR33","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1016\/j.clinre.2011.04.015","volume":"35","author":"J Aubert","year":"2011","unstructured":"Aubert J, Begriche K, Knockaert L, Robin MA, Fromenty B. Increased expression of cytochrome P450 2E1 in nonalcoholic fatty liver disease: mechanisms and pathophysiological role. Clin Res Hepatol Gastroenterol. 2011;35(10):630\u20137.","journal-title":"Clin Res Hepatol Gastroenterol"},{"issue":"3","key":"1912_CR34","doi-asserted-by":"publisher","first-page":"414","DOI":"10.3109\/13880209.2014.923002","volume":"53","author":"H Kang","year":"2015","unstructured":"Kang H, Koppula S. Houttuynia cordata alleviates high-fat diet-induced non-alcoholic fatty liver in experimental rats. Pharm Biol. 2015;53(3):414\u201322.","journal-title":"Pharm Biol"},{"key":"1912_CR35","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/j.talanta.2012.12.023","volume":"106","author":"JT Lee","year":"2013","unstructured":"Lee JT, Pao LH, Hsiong CH, Huang PW, Shih TY, Yoa-Pu HuO. Validated liquid chromatography-tandem mass spectrometry method for determination of totally nine probe metabolites of cytochrome P450 enzymes and UDP-glucuronosyltransferases. Talanta. 2013;106:220\u20138.","journal-title":"Talanta"},{"issue":"8","key":"1912_CR36","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1017\/S0007114516003391","volume":"116","author":"Y Choi","year":"2016","unstructured":"Choi Y, Lee JE, Chang Y, Kim MK, Sung E, Shin H, Ryu S. Dietary sodium and potassium intake in relation to non-alcoholic fatty liver disease. Br J Nutr. 2016;116(8):1447\u201356.","journal-title":"Br J Nutr"},{"issue":"11","key":"1912_CR37","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1038\/hr.2011.105","volume":"34","author":"H Takahashi","year":"2011","unstructured":"Takahashi H, Yoshika M, Komiyama Y, Nishimura M. The central mechanism underlying hypertension: a review of the roles of sodium ions, epithelial sodium channels, the renin\u2013angiotensin\u2013aldosterone system, oxidative stress and endogenous digitalis in the brain. Hypertens Res. 2011;34(11):1147\u201360.","journal-title":"Hypertens Res"},{"issue":"4","key":"1912_CR38","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1177\/1535370215611584","volume":"241","author":"WL Zheng","year":"2016","unstructured":"Zheng WL, Wang J, Mu JJ, Liu FQ, Yuan ZY, Wang Y, Wang D, Ren KY, Guo TS, Xiao HY. Effects of salt intake and potassium supplementation on renalase expression in the kidneys of Dahl salt-sensitive rats. Exp Biol Med. 2016;241(4):382\u20136.","journal-title":"Exp Biol Med"},{"issue":"1","key":"1912_CR39","doi-asserted-by":"publisher","first-page":"74","DOI":"10.3892\/ijmm.2015.2394","volume":"37","author":"Y Wu","year":"2016","unstructured":"Wu Y, Zhou J, Wang H, Wu Y, Gao Q, Wang L, Zhao Q, Liu P, Gao S, Wen W, et al. The activation of p38 MAPK limits the abnormal proliferation of vascular smooth muscle cells induced by high sodium concentrations. Int J Mol Med. 2016;37(1):74\u201382.","journal-title":"Int J Mol Med"},{"issue":"4","key":"1912_CR40","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1097\/FJC.0b013e3181f04b1c","volume":"56","author":"JM Williams","year":"2010","unstructured":"Williams JM, Murphy S, Burke M, Roman RJ. 20-hydroxyeicosatetraeonic acid: a new target for the treatment of hypertension. J Cardiovasc Pharmacol. 2010;56(4):336\u201344.","journal-title":"J Cardiovasc Pharmacol"}],"container-title":["BMC Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12876-021-01912-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12876-021-01912-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12876-021-01912-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T20:04:32Z","timestamp":1630181072000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcgastroenterol.biomedcentral.com\/articles\/10.1186\/s12876-021-01912-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,28]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1912"],"URL":"https:\/\/doi.org\/10.1186\/s12876-021-01912-4","relation":{},"ISSN":["1471-230X"],"issn-type":[{"value":"1471-230X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,28]]},"assertion":[{"value":"4 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 August 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":"All of the animal experiments were approved by and performed in accordance with the recommendations of the Academy of Military Medical Sciences Institutional Animal Care and Use Committee (IACUC-DWZX-2020-064). Animals were housed with a constant ambient temperature (23\u2009\u00b1\u20093\u00a0\u00b0C) and humidity (55%\u2009\u00b1\u20095%). Food, bedding, and water were changed every 4\u00a0days. All efforts were made to minimize suffering.","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 for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"335"}}