{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T11:30:49Z","timestamp":1772191849810,"version":"3.50.1"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T00:00:00Z","timestamp":1769817600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":27,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Mammary Gland Biol Neoplasia"],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Studies in breast cancer have demonstrated that apatinib exhibits both antiangiogenic and antitumor effects, while PD-L1 inhibitors have similarly shown meaningful clinical benefit. Building upon these observations, this study evaluated the potential synergistic antitumor effects of combining apatinib with a PD-L1 inhibitor and examined the mechanistic basis for their interaction in breast cancer. Notably, we found that this regimen could significantly suppress the proliferation, migration, and invasion of MCF-7 and MDA-MB-231 cells, and promote cell apoptosis. In addition, the levels of p-ERK, NF-\u03baB, and Slug were markedly reduced in vitro. Collectively, these findings support the potential clinical utility of combining apatinib and PD-L1 inhibition, as evidenced by consistent in vitro and in vivo synergy.<\/jats:p>","DOI":"10.1007\/s10911-026-09600-3","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T14:04:13Z","timestamp":1769868253000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synergistic Anticancer Effects of Apatinib and PD-L1 Inhibition in Breast Cancer"],"prefix":"10.1007","volume":"31","author":[{"given":"Danyang","family":"Han","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juanjuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cairu","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,31]]},"reference":[{"key":"9600_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-3-642-59953-8_1","volume":"237","author":"N Ferrara","year":"1999","unstructured":"Ferrara N. Vascular endothelial growth factor: molecular and biological aspects [J]. Curr Top Microbiol Immunol. 1999;237:1\u201330. https:\/\/doi.org\/10.1007\/978-3-642-59953-8_1.","journal-title":"Curr Top Microbiol Immunol"},{"issue":"1","key":"9600_CR2","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1186\/s12876-018-0870-3","volume":"18","author":"M Huang","year":"2018","unstructured":"Huang M, Huang B, Li G, Zeng S. Apatinib affect VEGF-mediated cell proliferation, migration, invasion via blocking VEGFR2\/RAF\/MEK\/ERK and PI3K\/AKT pathways in cholangiocarcinoma cells. BMC Gastroenterol. 2018;18(1):169. https:\/\/doi.org\/10.1186\/s12876-018-0870-3.","journal-title":"BMC Gastroenterol"},{"issue":"1","key":"9600_CR3","doi-asserted-by":"publisher","first-page":"e13924","DOI":"10.1097\/MD.0000000000013924","volume":"98","author":"YP Wu","year":"2019","unstructured":"Wu YP, Wu JJ, Tian SM, Jin T, Li C, Xie K. Apatinib with EGFR-TKIs in advanced wild gene-type NSCLC: A case report. Med (Baltim). 2019;98(1):e13924. https:\/\/doi.org\/10.1097\/MD.0000000000013924.","journal-title":"Med (Baltim)"},{"issue":"1","key":"9600_CR4","doi-asserted-by":"publisher","first-page":"e13491","DOI":"10.1097\/MD.0000000000013491","volume":"98","author":"J Jin","year":"2019","unstructured":"Jin J, Du J, Wu Y. Apatinib monotherapy for advanced VEGFR-2-negative nasopharyngeal carcinoma: A case report. Med (Baltim). 2019;98(1):e13491. https:\/\/doi.org\/10.1097\/MD.0000000000013491.","journal-title":"Med (Baltim)"},{"issue":"2","key":"9600_CR5","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/j.bbrc.2018.12.120","volume":"509","author":"Z Liu","year":"2019","unstructured":"Liu Z, Wang C, Wu G, Cheng J. MRI analysis of hydrogel-loaded apatinib for local therapy of hepatocellular carcinoma model in nude mice. Biochem Biophys Res Commun. 2019;509(2):529\u201334. https:\/\/doi.org\/10.1016\/j.bbrc.2018.12.120.","journal-title":"Biochem Biophys Res Commun"},{"key":"9600_CR6","doi-asserted-by":"publisher","unstructured":"Zou W, Chen L. Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol. 2008;8(6):467\u201377. https:\/\/doi.org\/10.1038\/nri2326.","DOI":"10.1038\/nri2326"},{"issue":"1","key":"9600_CR7","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1186\/s13045-017-0541-9","volume":"10","author":"B Liu","year":"2017","unstructured":"Liu B, Song Y, Liu D. Recent development in clinical applications of PD-1 and PD-L1 antibodies for cancer immunotherapy. J Hematol Oncol. 2017;10(1):174. https:\/\/doi.org\/10.1186\/s13045-017-0541-9.","journal-title":"J Hematol Oncol"},{"issue":"2","key":"9600_CR8","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.clcc.2023.03.001","volume":"22","author":"H Dedecker","year":"2023","unstructured":"Dedecker H, Teuwen LA, Vandamme T, Domen A, Prenen H. The role of immunotherapy in esophageal and gastric cancer. Clin Colorectal Cancer. 2023;22(2):175\u201382. https:\/\/doi.org\/10.1016\/j.clcc.2023.03.001.","journal-title":"Clin Colorectal Cancer"},{"key":"9600_CR9","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-017-0093-8","author":"LP Diggs","year":"2017","unstructured":"Diggs LP, Hsueh EC. Utility of PD-L1 immunohistochemistry assays for predicting PD-1\/PD-L1 inhibitor response. Biomark Res. 2017. https:\/\/doi.org\/10.1186\/s40364-017-0093-8. 5,12.","journal-title":"Biomark Res"},{"issue":"26","key":"9600_CR10","doi-asserted-by":"publisher","first-page":"2443","DOI":"10.1056\/NEJMoa1200690","volume":"366","author":"SL Topalian","year":"2012","unstructured":"Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, Mcdermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, Mcmiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, Mcdonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443\u201354. https:\/\/doi.org\/10.1056\/NEJMoa1200690.","journal-title":"N Engl J Med"},{"issue":"2","key":"9600_CR11","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1056\/NEJMoa1305133","volume":"369","author":"O Hamid","year":"2013","unstructured":"Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS, Dronca R, Gangadhar TC, Patnaik A, Zarour H, Joshua AM, Gergich K, Elassaiss-Schaap J, Algazi A, Mateus C, Boasberg P, Tumeh PC, Chmielowski B, Ebbinghaus SW, Li XN, Kang SP, Ribas A. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013;369(2):134\u201344. https:\/\/doi.org\/10.1056\/NEJMoa1305133.","journal-title":"N Engl J Med"},{"issue":"8","key":"9600_CR12","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1056\/NEJMoa1003466","volume":"363","author":"FS Hodi","year":"2010","unstructured":"Hodi FS, O\u2019day SJ, Mcdermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, Van Den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebb\u00e9 C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711\u201323. https:\/\/doi.org\/10.1056\/NEJMoa1003466.","journal-title":"N Engl J Med"},{"key":"9600_CR13","doi-asserted-by":"publisher","first-page":"1487526","DOI":"10.3389\/fmmed.2024.1487526","volume":"4","author":"C Schoenherr","year":"2025","unstructured":"Schoenherr C, Pietzsch S, Barca C, M\u00fcller FE, Bahr FS, Kasten M, Zeug A, Erschow S, Falk CS, Ponimaskin E, Thackeray JT, Hilfiker-Kleiner D, Ricke-Hoch M. Immune-checkpoint-inhibitor therapy directed against PD-L1 is tolerated in the heart without manifestation of cardiac inflammation in a preclinical reversible melanoma mouse model. Front Mol Med. 2025;4:1487526. https:\/\/doi.org\/10.3389\/fmmed.2024.1487526.","journal-title":"Front Mol Med"},{"issue":"6","key":"9600_CR14","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1634\/theoncologist.2014-0002","volume":"19","author":"M Bonotto","year":"2014","unstructured":"Bonotto M, Gerratana L, Poletto E, Driol P, Giangreco M, Russo S, Minisini AM, Andreetta C, Mansutti M, Pisa FE, Fasola G, Puglisi F. Measures of outcome in metastatic breast cancer: insights from a real-world scenario. Oncologist. 2014;19(6):608\u201315. https:\/\/doi.org\/10.1634\/theoncologist.2014-0002.","journal-title":"Oncologist"},{"issue":"8","key":"9600_CR15","doi-asserted-by":"publisher","first-page":"e3015","DOI":"10.1038\/cddis.2017.422","volume":"8","author":"K Liu","year":"2017","unstructured":"Liu K, Ren T, Huang Y, Sun K, Bao X, Wang S, Zheng B, Guo W. Apatinib promotes autophagy and apoptosis through VEGFR2\/STAT3\/BCL-2 signaling in osteosarcoma. Cell Death Dis. 2017;8(8):e3015. https:\/\/doi.org\/10.1038\/cddis.2017.422.","journal-title":"Cell Death Dis"},{"issue":"3","key":"9600_CR16","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1158\/1078-0432.CCR-16-3001","volume":"24","author":"LA Emens","year":"2018","unstructured":"Emens LA. Breast cancer immunotherapy: facts and hopes. Clin Cancer Res. 2018;24(3):511\u201320. https:\/\/doi.org\/10.1158\/1078-0432.CCR-16-3001.","journal-title":"Clin Cancer Res"},{"key":"9600_CR17","doi-asserted-by":"publisher","unstructured":"Yu X, Fan H, Jiang X, Zheng W, Yang Y, Jin M, Ma X, Jiang W. Apatinib induces apoptosis and autophagy via the PI3K\/AKT\/mTOR and MAPK\/ERK signaling pathways in neuroblastoma. Oncol Lett. 2020;20(4):52. https:\/\/doi.org\/10.3892\/ol.2020.11913.","DOI":"10.3892\/ol.2020.11913"},{"issue":"5 Pt A","key":"9600_CR18","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1016\/j.bbadis.2018.03.002","volume":"1864","author":"XY Qiu","year":"2018","unstructured":"Qiu XY, Hu DX, Chen WQ, Chen RQ, Qian SR, Li CY, Li YJ, Xiong XX, Liu D, Pan F, Yu SB, Chen XQ. PD-L1 confers glioblastoma multiforme malignancy via Ras binding and Ras\/Erk\/EMT activation. Biochim Biophys Acta Mol Basis Dis. 2018;1864(5 Pt A):1754\u201369. https:\/\/doi.org\/10.1016\/j.bbadis.2018.03.002.","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"9600_CR19","doi-asserted-by":"publisher","unstructured":"Zhao W, Ma N, Wang S, Mo Y, Zhang Z, Huang G, Midorikawa K, Hiraku Y, Oikawa S, Murata M, Takeuchi K. RERG suppresses cell proliferation, migration and angiogenesis through ERK\/NF-\u03baB signaling pathway in nasopharyngeal carcinoma. J Exp Clin Cancer Res. 2017;36(1):88. https:\/\/doi.org\/10.1186\/s13046-017-0554-9.","DOI":"10.1186\/s13046-017-0554-9"},{"issue":"1","key":"9600_CR20","doi-asserted-by":"publisher","first-page":"e0169622","DOI":"10.1371\/journal.pone.0169622","volume":"12","author":"BR Pires","year":"2017","unstructured":"Pires BR, Mencalha AL, Ferreira GM, De Souza WF, Morgado-D\u00edaz JA, Maia AM, Corr\u00eaa S, Abdelhay ES. NF-kappaB is involved in the regulation of EMT genes in breast cancer cells. PLoS ONE. 2017;12(1):e0169622. https:\/\/doi.org\/10.1371\/journal.pone.0169622.","journal-title":"PLoS ONE"},{"issue":"4","key":"9600_CR21","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1158\/2326-6066.CIR-17-0640","volume":"7","author":"S Zhao","year":"2019","unstructured":"Zhao S, Ren S, Jiang T, Zhu B, Li X, Zhao C, Jia Y, Shi J, Zhang L, Liu X, Qiao M, Chen X, Su C, Yu H, Zhou C, Zhang J, Camidge DR, Hirsch FR. Low-Dose apatinib optimizes tumor microenvironment and potentiates antitumor effect of PD-1\/PD-L1 Blockade in lung cancer. Cancer Immunol Res. 2019;7(4):630\u201343. https:\/\/doi.org\/10.1158\/2326-6066.CIR-17-0640.","journal-title":"Cancer Immunol Res"},{"issue":"8","key":"9600_CR22","doi-asserted-by":"publisher","first-page":"2209","DOI":"10.1007\/s00432-021-03633-3","volume":"147","author":"Y Zhang","year":"2021","unstructured":"Zhang Y, Wang F, Sun HR, Huang YK, Gao JP, Huang H. Apatinib combined with PD-L1 Blockade synergistically enhances antitumor immune responses and promotes HEV formation in gastric cancer. J Cancer Res Clin Oncol. 2021;147(8):2209\u201322. https:\/\/doi.org\/10.1007\/s00432-021-03633-3.","journal-title":"J Cancer Res Clin Oncol"},{"issue":"5","key":"9600_CR23","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1158\/1078-0432.CCR-20-3136","volume":"27","author":"C Zhou","year":"2021","unstructured":"Zhou C, Wang Y, Zhao J, Chen G, Liu Z, Gu K, Huang M, He J, Chen J, Ma Z, Feng J, Shi J, Yu X, Cheng Y, Yao Y, Chen Y, Guo R, Lin X, Wang Z, Gao G, Wang Q, Li W, Yang X, Wu L, Zhang J, Ren S. Efficacy and biomarker analysis of camrelizumab in combination with apatinib in patients with advanced nonsquamous NSCLC previously treated with chemotherapy. Clin Cancer Res. 2021;27(5):1296\u2013304. https:\/\/doi.org\/10.1158\/1078-0432.CCR-20-3136.","journal-title":"Clin Cancer Res"},{"issue":"385","key":"9600_CR24","doi-asserted-by":"publisher","first-page":"eaak9670","DOI":"10.1126\/scitranslmed.aak9670","volume":"9","author":"M Schmittnaegel","year":"2017","unstructured":"Schmittnaegel M, Rigamonti N, Kadioglu E, Cassar\u00e1 A, Wyser Rmili C, Kiialainen A, Kienast Y, Mueller HJ, Ooi CH, Laoui D, De Palma M. Dual angiopoietin-2 and VEGFA Inhibition elicits antitumor immunity that is enhanced by PD-1 checkpoint Blockade. Sci Transl Med. 2017;9(385):eaak9670. https:\/\/doi.org\/10.1126\/scitranslmed.aak9670.","journal-title":"Sci Transl Med"},{"issue":"385","key":"9600_CR25","doi-asserted-by":"publisher","first-page":"eaak9679","DOI":"10.1126\/scitranslmed.aak9679","volume":"9","author":"E Allen","year":"2017","unstructured":"Allen E, Jabouille A, Rivera LB, Lodewijckx I, Missiaen R, Steri V, Feyen K, Tawney J, Hanahan D, Michael IP, Bergers G. Combined antiangiogenic and anti-PD-L1 therapy stimulates tumor immunity through HEV formation. Sci Transl Med. 2017;9(385):eaak9679. https:\/\/doi.org\/10.1126\/scitranslmed.aak9679.","journal-title":"Sci Transl Med"},{"issue":"9","key":"9600_CR26","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1007\/s00262-020-02576-x","volume":"69","author":"Q Wang","year":"2020","unstructured":"Wang Q, Gao J, Di W, Wu X. Anti-angiogenesis therapy overcomes the innate resistance to PD-1\/PD-L1 Blockade in VEGFA-overexpressed mouse tumor models. Cancer Immunol Immunother. 2020;69(9):1781\u201399. https:\/\/doi.org\/10.1007\/s00262-020-02576-x.","journal-title":"Cancer Immunol Immunother"},{"issue":"7193","key":"9600_CR27","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1038\/nature06868","volume":"453","author":"J Hamzah","year":"2008","unstructured":"Hamzah J, Jugold M, Kiessling F, Rigby P, Manzur M, Marti HH, Rabie T, Kaden S, Gr\u00f6ne HJ, H\u00e4mmerling GJ, Arnold B, Ganss R. Vascular normalization in Rgs5-deficient tumours promotes immune destruction. Nature. 2008;453(7193):410\u20134. https:\/\/doi.org\/10.1038\/nature06868.","journal-title":"Nature"},{"issue":"43","key":"9600_CR28","doi-asserted-by":"publisher","first-page":"17561","DOI":"10.1073\/pnas.1215397109","volume":"109","author":"Y Huang","year":"2012","unstructured":"Huang Y, Yuan J, Righi E, Kamoun WS, Ancukiewicz M, Nezivar J, Santosuosso M, Martin JD, Martin MR, Vianello F, Leblanc P, Munn LL, Huang P, Duda DG, Fukumura D, Jain RK, Poznansky MC. Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy. Proc Natl Acad Sci USA. 2012;109(43):17561\u20136. https:\/\/doi.org\/10.1073\/pnas.1215397109.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"7","key":"9600_CR29","first-page":"4460","volume":"11","author":"H Zhang","year":"2019","unstructured":"Zhang H, Sun J, Ju W, Li B, Lou Y, Zhang G, Liang G, Luo X. Apatinib suppresses breast cancer cells proliferation and invasion via Angiomotin Inhibition. Am J Transl Res. 2019;11(7):4460\u20139.","journal-title":"Am J Transl Res"},{"issue":"3","key":"9600_CR30","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1007\/s10549-017-4537-5","volume":"167","author":"LY Dirix","year":"2018","unstructured":"Dirix LY, Takacs I, Jerusalem G, Nikolinakos P, Arkenau HT, Forero-Torres A, Boccia R, Lippman ME, Somer R, Smakal M, Emens LA, Hrinczenko B, Edenfield W, Gurtler J, Von Heydebreck A, Grote HJ, Chin K, Hamilton EP. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN solid tumor study]. Breast Cancer Res Treat. 2018;167(3):671\u201386. https:\/\/doi.org\/10.1007\/s10549-017-4537-5.","journal-title":"Breast Cancer Res Treat"},{"key":"9600_CR31","doi-asserted-by":"publisher","unstructured":"Heidegger S, Wintges A, Stritzke F, Bek S, Steiger K, Koenig PA, G\u00f6ttert S, Engleitner T, \u00d6llinger R, Nedelko T, Fischer JC, Makarov V, Winter C, Rad R, Van Den Brink MRM, Ruland J, Bassermann F, Chan TA, Haas T, Poeck H. RIG-I activation is critical for responsiveness to checkpoint Blockade. Sci Immunol. 2019;4(39). https:\/\/doi.org\/10.1126\/sciimmunol.aau8943.","DOI":"10.1126\/sciimmunol.aau8943"},{"issue":"17","key":"9600_CR32","doi-asserted-by":"publisher","first-page":"7559","DOI":"10.1128\/MCB.24.17.7559-7566.2004","volume":"24","author":"M Kajita","year":"2004","unstructured":"Kajita M, Mcclinic KN, Wade PA. Aberrant expression of the transcription factors snail and slug alters the response to genotoxic stress. Mol Cell Biol. 2004;24(17):7559\u201366. https:\/\/doi.org\/10.1128\/MCB.24.17.7559-7566.2004.","journal-title":"Mol Cell Biol"},{"key":"9600_CR33","doi-asserted-by":"publisher","first-page":"109167","DOI":"10.1016\/j.intimp.2022.109167","volume":"112","author":"X Luo","year":"2022","unstructured":"Luo X, Zou W, Wei Z, et al. Inducing vascular normalization: A promising strategy for immunotherapy. Int Immunopharmacol. 2022;112:109167. https:\/\/doi.org\/10.1016\/j.intimp.2022.109167.","journal-title":"Int Immunopharmacol"}],"container-title":["Journal of Mammary Gland Biology and Neoplasia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10911-026-09600-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10911-026-09600-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10911-026-09600-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T10:38:23Z","timestamp":1772188703000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10911-026-09600-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,31]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["9600"],"URL":"https:\/\/doi.org\/10.1007\/s10911-026-09600-3","relation":{},"ISSN":["1083-3021","1573-7039"],"issn-type":[{"value":"1083-3021","type":"print"},{"value":"1573-7039","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,31]]},"assertion":[{"value":"2 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Medical Ethics Committee of Luoyang Central Hospital (Approval No.: LWLL-2024-11-05-01), and all procedures were conducted in accordance with the institutional animal guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"6"}}