{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T03:06:07Z","timestamp":1779937567671,"version":"3.53.1"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:00:00Z","timestamp":1775865600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":47,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100017695","name":"Health Commission of Hunan Province","doi-asserted-by":"crossref","award":["20255960"],"award-info":[{"award-number":["20255960"]}],"id":[{"id":"10.13039\/100017695","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004761","name":"Provincial Natural Science Foundation of Hunan","doi-asserted-by":"crossref","award":["2025JJ50518"],"award-info":[{"award-number":["2025JJ50518"]}],"id":[{"id":"10.13039\/501100004761","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Women's Health"],"DOI":"10.1186\/s12905-026-04409-y","type":"journal-article","created":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T03:25:03Z","timestamp":1775877903000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unraveling the fibrotic microenvironment in intrauterine adhesions through integrated metabolomics and proteomics"],"prefix":"10.1186","volume":"26","author":[{"given":"Shuhan","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingping","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enuo","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dabao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiqian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,11]]},"reference":[{"issue":"1","key":"4409_CR1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s00281-024-01030-9","volume":"47","author":"G Zhao","year":"2024","unstructured":"Zhao G, Hu Y. Mechanistic insights into intrauterine adhesions. Semin Immunopathol. 2024;47(1):3.","journal-title":"Semin Immunopathol"},{"key":"4409_CR2","doi-asserted-by":"crossref","unstructured":"Lee W-L, Liu C-H, Cheng M et al. Focus on the primary prevention of intrauterine adhesions: current concept and vision. Int J Mol Sci, 2021, 22(10).","DOI":"10.3390\/ijms22105175"},{"issue":"3","key":"4409_CR3","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/j.tjog.2024.02.004","volume":"63","author":"P-H Wang","year":"2024","unstructured":"Wang P-H, Yang S-T, Chang W-H, et al. Intrauterine adhesion. Taiwan J Obstet Gynecol. 2024;63(3):312\u20139.","journal-title":"Taiwan J Obstet Gynecol"},{"key":"4409_CR4","doi-asserted-by":"crossref","unstructured":"Zhu H, Li T, Xu P et al. Effect of autologous bone marrow stem cells-scaffold transplantation on the ongoing pregnancy rate in intrauterine adhesion women: a randomized, controlled trial. Sci China Life Sci, 2023.","DOI":"10.1007\/s11427-023-2403-7"},{"issue":"1","key":"4409_CR5","first-page":"70","volume":"36","author":"AB Hooker","year":"2021","unstructured":"Hooker AB, de Leeuw RA, Twisk JWR, et al. Reproductive performance of women with and without intrauterine adhesions following recurrent dilatation and curettage for miscarriage: long-term follow-up of a randomized controlled trial. Hum Reprod. 2021;36(1):70\u201381.","journal-title":"Hum Reprod"},{"issue":"1","key":"4409_CR6","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s40824-021-00242-6","volume":"25","author":"J Ma","year":"2021","unstructured":"Ma J, Zhan H, Li W, et al. Recent trends in therapeutic strategies for repairing endometrial tissue in intrauterine adhesion. Biomater Res. 2021;25(1):40.","journal-title":"Biomater Res"},{"issue":"3","key":"4409_CR7","doi-asserted-by":"publisher","first-page":"202","DOI":"10.4103\/gmit.gmit_120_23","volume":"13","author":"X Liu","year":"2024","unstructured":"Liu X, Zhang X, Hua K. Hysteroscopic surgery for intrauterine scar adhesions after laparoscopic metroplasty in a patient with a unicornuate uterus and a functional noncommunicating rudimentary horn. Gynecol Minim Invasive Ther. 2024;13(3):202\u20133.","journal-title":"Gynecol Minim Invasive Ther"},{"issue":"2","key":"4409_CR8","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1016\/j.fertnstert.2024.03.016","volume":"122","author":"J Zhang","year":"2024","unstructured":"Zhang J, Shi C, Sun J, et al. Analysis of factors affecting the prognosis of patients with intrauterine adhesions after transcervical resection of adhesions. Fertil Steril. 2024;122(2):365\u201372.","journal-title":"Fertil Steril"},{"issue":"1","key":"4409_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/03630242.2022.2144984","volume":"63","author":"J Zhao","year":"2022","unstructured":"Zhao J, Zhang L, Liang J, et al. The effect of the combined use of an intrauterine device and a Foley balloon in the prevention of adhesion following hysteroscopic adhesiolysis. Women Health. 2022;63(1):1\u20137.","journal-title":"Women Health"},{"issue":"1","key":"4409_CR10","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1186\/s12905-022-01940-6","volume":"22","author":"Y Sun","year":"2022","unstructured":"Sun Y, Chen X, Qian Z, et al. Estradiol and intrauterine device treatment for moderate and severe intrauterine adhesions after transcervical resection. BMC Womens Health. 2022;22(1):357.","journal-title":"BMC Womens Health"},{"key":"4409_CR11","doi-asserted-by":"crossref","unstructured":"Luo Y, Sun Y, Huang B et al. Effects and safety of hyaluronic acid gel on intrauterine adhesion and fertility after intrauterine surgery: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials. Am J Obstet Gynecol, 2024, 231(1).","DOI":"10.1016\/j.ajog.2023.12.039"},{"issue":"23","key":"4409_CR12","doi-asserted-by":"publisher","first-page":"11002","DOI":"10.1111\/jcmm.17023","volume":"25","author":"J Yu","year":"2021","unstructured":"Yu J, Zhang W, Huang J, et al. Management of intrauterine adhesions using human amniotic mesenchymal stromal cells to promote endometrial regeneration and repair through Notch signalling. J Cell Mol Med. 2021;25(23):11002\u201315.","journal-title":"J Cell Mol Med"},{"issue":"1","key":"4409_CR13","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1186\/s40001-022-00767-z","volume":"27","author":"C Cao","year":"2022","unstructured":"Cao C, Zhou Q, Hu Z, et al. A retrospective study of estrogen in the pretreatment for medical management of early pregnancy loss and the inference from intrauterine adhesion. Eur J Med Res. 2022;27(1):129.","journal-title":"Eur J Med Res"},{"issue":"1","key":"4409_CR14","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1186\/s13287-021-02620-2","volume":"12","author":"Y-T Song","year":"2021","unstructured":"Song Y-T, Liu P-C, Tan J, et al. Stem cell-based therapy for ameliorating intrauterine adhesion and endometrium injury. Stem Cell Res Ther. 2021;12(1):556.","journal-title":"Stem Cell Res Ther"},{"issue":"7","key":"4409_CR15","first-page":"521","volume":"31","author":"L Liu","year":"2022","unstructured":"Liu L, Yan S, Qiu T, et al. Study on the endometrial metabolomics of intrauterine adhesions. Progress Obstet Gynecol. 2022;31(7):521\u20135.","journal-title":"Progress Obstet Gynecol"},{"key":"4409_CR16","doi-asserted-by":"publisher","first-page":"114532","DOI":"10.1016\/j.jpba.2021.114532","volume":"209","author":"L Li","year":"2022","unstructured":"Li L, Deng J, Lin L-M, et al. Metabolomics and pharmacodynamic analysis reveal the therapeutic role of Prunella vulgaris oil on intrauterine adhesion rats. J Pharm Biomed Anal. 2022;209:114532.","journal-title":"J Pharm Biomed Anal"},{"key":"4409_CR17","doi-asserted-by":"crossref","unstructured":"Rozanova S, Barkovits K, Nikolov M et al. Quantitative Mass Spectrometry-Based Proteomics: An Overview. Methods Mol Biol. 2021;2228.","DOI":"10.1007\/978-1-0716-1024-4_8"},{"issue":"7","key":"4409_CR18","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1016\/j.cmet.2024.05.003","volume":"36","author":"P Horn","year":"2024","unstructured":"Horn P, Tacke F. Metabolic reprogramming in liver fibrosis. Cell Metab. 2024;36(7):1439\u201355.","journal-title":"Cell Metab"},{"issue":"1","key":"4409_CR19","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1038\/s41590-022-01365-1","volume":"24","author":"K Tang","year":"2023","unstructured":"Tang K, Zhang H, Deng J, et al. Ammonia detoxification promotes CD8\u2009+\u2009T cell memory development by urea and citrulline cycles. Nat Immunol. 2023;24(1):162\u201373.","journal-title":"Nat Immunol"},{"issue":"2","key":"4409_CR20","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/s00726-021-03097-2","volume":"54","author":"MA Elmetwally","year":"2021","unstructured":"Elmetwally MA, Li X, Johnson GA, et al. Dietary supplementation with L-arginine between days 14 and 25 of gestation enhances NO and polyamine syntheses and the expression of angiogenic proteins in porcine placentae. Amino Acids. 2021;54(2):193\u2013204.","journal-title":"Amino Acids"},{"issue":"1","key":"4409_CR21","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1186\/s13287-021-02499-z","volume":"12","author":"Y Zhang","year":"2021","unstructured":"Zhang Y, Shi L, Lin X, et al. Unresponsive thin endometrium caused by Asherman syndrome treated with umbilical cord mesenchymal stem cells on collagen scaffolds: a pilot study. Stem Cell Res Ther. 2021;12(1):420.","journal-title":"Stem Cell Res Ther"},{"key":"4409_CR22","doi-asserted-by":"crossref","unstructured":"Varghese N, Werner S, Grimm A et al. Dietary Mitophagy Enhancer: A Strategy for Healthy Brain Aging? Antioxid (Basel). 2020;9(10).","DOI":"10.3390\/antiox9100932"},{"issue":"4","key":"4409_CR23","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1016\/j.ymthe.2021.01.028","volume":"29","author":"J-M Li","year":"2021","unstructured":"Li J-M, Yang DC, Oldham J, et al. Therapeutic targeting of argininosuccinate synthase 1 (ASS1)-deficient pulmonary fibrosis. Mol Ther. 2021;29(4):1487\u2013500.","journal-title":"Mol Ther"},{"issue":"1","key":"4409_CR24","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s12951-021-01122-w","volume":"20","author":"M Wang","year":"2022","unstructured":"Wang M, Zeng F, Ning F, et al. Ceria nanoparticles ameliorate renal fibrosis by modulating the balance between oxidative phosphorylation and aerobic glycolysis. J Nanobiotechnol. 2022;20(1):3.","journal-title":"J Nanobiotechnol"},{"issue":"1","key":"4409_CR25","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1038\/s41392-022-01097-6","volume":"7","author":"H Zeng","year":"2022","unstructured":"Zeng H, Pan T, Zhan M, et al. Suppression of PFKFB3-driven glycolysis restrains endothelial-to-mesenchymal transition and fibrotic response. Signal Transduct Target Ther. 2022;7(1):303.","journal-title":"Signal Transduct Target Ther"},{"issue":"2","key":"4409_CR26","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1002\/jbm.a.37604","volume":"112","author":"S Song","year":"2024","unstructured":"Song S, Wu S, Meiduo D, et al. Nano-biomaterial Fibrinogen\/P(LLA-CL) for prevention of intrauterine adhesion and restoration of fertility. J Biomed Mater Res A. 2024;112(2):167\u201379.","journal-title":"J Biomed Mater Res A"},{"key":"4409_CR27","doi-asserted-by":"crossref","unstructured":"Yang W, Pan L, Cheng Y et al. Nintedanib alleviates pulmonary fibrosis in vitro and in vivo by inhibiting the FAK\/ERK\/S100A4 signalling pathway. Int Immunopharmacol. 2022;113(Pt A):09409.","DOI":"10.1016\/j.intimp.2022.109409"},{"key":"4409_CR28","doi-asserted-by":"crossref","unstructured":"Chen W-C, Yu W-K, Su V, Y-F et al. NLRP3 Inflammasome Activates Endothelial-to-Mesenchymal Transition via Focal Adhesion Kinase Pathway in Bleomycin-Induced Pulmonary Fibrosis. Int J Mol Sci. 2023;24(21).","DOI":"10.3390\/ijms242115813"},{"issue":"8","key":"4409_CR29","doi-asserted-by":"publisher","first-page":"2394","DOI":"10.7150\/ijbs.77649","volume":"19","author":"Y Huang","year":"2023","unstructured":"Huang Y, Zhao H, Zhang Y, et al. Enhancement of Zyxin Promotes Skin Fibrosis by Regulating FAK\/PI3K\/AKT and TGF-\u03b2 Signaling Pathways via Integrins. Int J Biol Sci. 2023;19(8):2394\u2013408.","journal-title":"Int J Biol Sci"},{"issue":"7","key":"4409_CR30","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1007\/s43032-019-00044-1","volume":"27","author":"T Nagai","year":"2020","unstructured":"Nagai T, Ishida C, Nakamura T, et al. Focal Adhesion Kinase-Mediated Sequences, Including Cell Adhesion, Inflammatory Response, and Fibrosis, as a Therapeutic Target in Endometriosis. Reprod Sci. 2020;27(7):1400\u201310.","journal-title":"Reprod Sci"},{"issue":"5","key":"4409_CR31","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1002\/jor.25762","volume":"42","author":"HN Chang","year":"2024","unstructured":"Chang HN, Chen CK, Yu TY, et al. Lidocaine inhibits migration of tenocytes by downregulating focal adhesion kinase and paxillin phosphorylation. J Orthop Res. 2024;42(5):985\u201392.","journal-title":"J Orthop Res"},{"key":"4409_CR32","doi-asserted-by":"publisher","first-page":"110437","DOI":"10.1016\/j.cellsig.2022.110437","volume":"99","author":"K Kitsugi","year":"2022","unstructured":"Kitsugi K, Noritake H, Matsumoto M, et al. Arg-Gly-Asp-binding integrins activate hepatic stellate cells via the hippo signaling pathway. Cell Signal. 2022;99:110437.","journal-title":"Cell Signal"},{"issue":"6","key":"4409_CR33","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1038\/s41374-020-0404-9","volume":"100","author":"X Hu","year":"2020","unstructured":"Hu X, Xu Q, Wan H, et al. PI3K-Akt-mTOR\/PFKFB3 pathway mediated lung fibroblast aerobic glycolysis and collagen synthesis in lipopolysaccharide-induced pulmonary fibrosis. Lab Invest. 2020;100(6):801\u201311.","journal-title":"Lab Invest"},{"key":"4409_CR34","doi-asserted-by":"crossref","unstructured":"Guo Z, Wang Y, Wen X et al. \u03b2-Klotho Promotes the Development of Intrauterine Adhesions via the PI3K\/AKT Signaling Pathway. Int J Mol Sci. 2022;23(19).","DOI":"10.3390\/ijms231911294"},{"key":"4409_CR35","doi-asserted-by":"publisher","first-page":"5643","DOI":"10.2147\/IJN.S137237","volume":"12","author":"S-S Zhang","year":"2017","unstructured":"Zhang S-S, Xia W-T, Xu J, et al. Three-dimensional structure micelles of heparin-poloxamer improve the therapeutic effect of 17\u03b2-estradiol on endometrial regeneration for intrauterine adhesions in a rat model. Int J Nanomed. 2017;12:5643\u201357.","journal-title":"Int J Nanomed"},{"issue":"2","key":"4409_CR36","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1093\/humrep\/dey344","volume":"34","author":"Z Zhu","year":"2019","unstructured":"Zhu Z, Zhang Y, Zhang Y, et al. Exosomes derived from human umbilical cord mesenchymal stem cells accelerate growth of VK2 vaginal epithelial cells through MicroRNAs in vitro. Hum Reprod. 2019;34(2):248\u201360.","journal-title":"Hum Reprod"}],"container-title":["BMC Women's Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12905-026-04409-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12905-026-04409-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12905-026-04409-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T02:55:29Z","timestamp":1779936929000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12905-026-04409-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,11]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4409"],"URL":"https:\/\/doi.org\/10.1186\/s12905-026-04409-y","relation":{},"ISSN":["1472-6874"],"issn-type":[{"value":"1472-6874","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,11]]},"assertion":[{"value":"27 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 April 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 performed in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the Third Xiangya Hospital (Approval No. Kua 24558). All participants gave informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"271"}}