{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:29:17Z","timestamp":1790994557913,"version":"4.1.0"},"reference-count":25,"publisher":"Georg Thieme Verlag KG","issue":"06","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"crossref","award":["82260391"],"award-info":[{"award-number":["82260391"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82372541"],"award-info":[{"award-number":["82372541"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Talent Team Construction Project for Basic and Clinical Research on Lymphedema of Guizhou Province x","award":["Qiankehe Talent CXTD [2025] 051"],"award-info":[{"award-number":["Qiankehe Talent CXTD [2025] 051"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Reconstr Microsurg"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Secondary extremity lymphedema is a chronic and progressive condition caused by obstructed lymphatic drainage, commonly following lymphadenectomy, infection, or trauma. Rodent models are preferred for experimental lymphedema research due to cost-effectiveness and reproducibility. Currently, rat tail models encounter limitations due to transient swelling and their inability to fully replicate the comprehensive pathophysiology of lymphedema, particularly concerning the effects of lymph node removal.<\/jats:p>\n                  <jats:p>We developed a series of rat tail lymphedema models incorporating skin resection, deep lymphatic vessel disruption, and gluteal lymph node (GLN) excision to assess effects on lymphatic architecture, inflammation, and fibrosis. Indocyanine green (ICG) lymphography was used to visualize lymphatic function. Tail volume and circumference were measured weekly, and histological assessments quantified fibrosis and fibroadipose thickening. Bulk RNA sequencing was performed to characterize the inflammatory processes triggered by GLN removal.<\/jats:p>\n                  <jats:p>The combined model (skin removal, deep lymphatic disruption, and GLN excision) resulted in severe and persistent lymphedema marked by progressive swelling and pronounced fibrosis. ICG lymphography confirmed disruption of superficial lymphatic flow with partial recanalization of deep channels. Notably, lymphangiogenesis was observed at the GLN excision site, forming compensatory pathways connecting the tail to the popliteal lymph nodes. Histology revealed extensive collagen deposition and fibroadipose thickening in groups with lymph node removal, with the combined model showing the most pronounced changes. Bulk RNA-sequencing confirmed the removal of GLN involving the inflammatory and fibrosis process in the tail model.<\/jats:p>\n                  <jats:p>This lymphosome-based rat tail model successfully replicates key features of lymphedema, including sustained swelling, lymphatic disruption, inflammation, and fibrosis.<\/jats:p>","DOI":"10.1055\/a-2687-0506","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T23:15:21Z","timestamp":1755818121000},"page":"466-472","source":"Crossref","is-referenced-by-count":3,"title":["A Novel Lymphosome-Based Long-Lasting Rat Tail Model of Lymphedema"],"prefix":"10.1055","volume":"42","author":[{"given":"Junzhe","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilin","family":"Tu","sequence":"additional","affiliation":[{"name":"Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haokun","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyao","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuezhong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shune","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China"},{"name":"The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, Zunyi, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengliang","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China"},{"name":"The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, Zunyi, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"issue":"01","key":"ref1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1146\/annurev-med-060116-022900","article-title":"Lymphedema: Pathogenesis and novel therapies","volume":"69","author":"J H Dayan","year":"2018","journal-title":"Annu Rev Med"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jss.2021.10.021","article-title":"Animal models used in the research of vascularized lymph node transfer: A systematic review","volume":"272","author":"K Stanek","year":"2022","journal-title":"J Surg Res"},{"issue":"01","key":"ref3","doi-asserted-by":"crossref","first-page":"e31088","DOI":"10.1002\/micr.31088","article-title":"Surgical lymphedema models in the mice hindlimb-A systematic review and quality assessment","volume":"44","author":"A Bucan","year":"2024","journal-title":"Microsurgery"},{"issue":"04","key":"ref4","doi-asserted-by":"crossref","first-page":"166","DOI":"10.5625\/lar.2015.31.4.166","article-title":"Comparative analysis of growth characteristics of Sprague Dawley rats obtained from different sources","volume":"31","author":"M Brower","year":"2015","journal-title":"Lab Anim Res"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"S129","DOI":"10.1097\/SAP.0000000000002323","article-title":"Creation of a rat lower limb lymphedema model","volume":"85","author":"A A Harb","year":"2020","journal-title":"Ann Plast Surg"},{"issue":"12","key":"ref6","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1002\/cncr.22684","article-title":"Lymphedema after gynecological cancer treatment: prevalence, correlates, and supportive care needs","volume":"109","author":"V Beesley","year":"2007","journal-title":"Cancer"},{"issue":"06","key":"ref7","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/S1470-2045(13)70076-7","article-title":"Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis","volume":"14","author":"T DiSipio","year":"2013","journal-title":"Lancet Oncol"},{"issue":"09","key":"ref8","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1002\/ar.21446","article-title":"Demonstrating the lymphatic system in rats with microinjection","volume":"294","author":"H Suami","year":"2011","journal-title":"Anat Rec (Hoboken)"},{"issue":"09","key":"ref9","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1038\/s41423-024-01188-0","article-title":"Innate and adaptive immune responses that control lymph-borne viruses in the draining lymph node","volume":"21","author":"C R Melo-Silva","year":"2024","journal-title":"Cell Mol Immunol"},{"key":"ref10","first-page":"15","article-title":"The role of escin as a topical agent for lymphedema treatment in a rat model","author":"H H Jeong","year":"2023","journal-title":"Int J Low Extrem Wounds"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1173169","DOI":"10.3389\/fbioe.2023.1173169","article-title":"Low-intensity pulsed ultrasound reduces lymphedema by regulating macrophage polarization and enhancing microcirculation","volume":"11","author":"Z Liu","year":"2023","journal-title":"Front Bioeng Biotechnol"},{"issue":"06","key":"ref12","doi-asserted-by":"crossref","first-page":"1128e","DOI":"10.1097\/PRS.0000000000011363","article-title":"Metformin eliminates lymphedema in mice by alleviating inflammation and fibrosis: implications for human therapy","volume":"154","author":"M Wei","year":"2024","journal-title":"Plast Reconstr Surg"},{"issue":"05","key":"ref13","doi-asserted-by":"crossref","first-page":"101905","DOI":"10.1016\/j.jvsv.2024.101905","article-title":"Synchronous supraclavicular vascularized lymph node transfer and liposuction for gynecological cancer-related lower extremity lymphedema: A clinical comparative analysis of three different procedures","volume":"12","author":"M Wei","year":"2024","journal-title":"J Vasc Surg Venous Lymphat Disord"},{"issue":"05","key":"ref14","doi-asserted-by":"crossref","first-page":"904e","DOI":"10.1097\/PRS.0000000000010434","article-title":"Lymph node transfer and neolymphangiogenesis: From theory to evidence","volume":"152","author":"M Maruccia","year":"2023","journal-title":"Plast Reconstr Surg"},{"issue":"02","key":"ref15","doi-asserted-by":"crossref","first-page":"104","DOI":"10.3390\/jfb14020104","article-title":"A novel dressing composed of adipose stem cells and decellularized Wharton's jelly facilitated wound healing and relieved lymphedema by enhancing angiogenesis and lymphangiogenesis in a rat model","volume":"14","author":"J H Lu","year":"2023","journal-title":"J Funct Biomater"},{"issue":"01","key":"ref16","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.jss.2013.11.1116","article-title":"Cell transplantation therapy for a rat model of secondary lymphedema","volume":"189","author":"Y Kawai","year":"2014","journal-title":"J Surg Res"},{"issue":"11","key":"ref17","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1161\/CIRCULATIONAHA.105.602953","article-title":"Transfection of human hepatocyte growth factor gene ameliorates secondary lymphedema via promotion of lymphangiogenesis","volume":"114","author":"Y Saito","year":"2006","journal-title":"Circulation"},{"issue":"08","key":"ref18","doi-asserted-by":"crossref","first-page":"e196","DOI":"10.1097\/GOX.0000000000000154","article-title":"Topical bFGF improves secondary lymphedema through lymphangiogenesis in a rat tail model","volume":"2","author":"T Onishi","year":"2014","journal-title":"Plast Reconstr Surg Glob Open"},{"issue":"08","key":"ref19","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1089\/wound.2021.0033","article-title":"Current advancements in animal models of postsurgical lymphedema: A systematic review","volume":"11","author":"J F Hsu","year":"2022","journal-title":"Adv Wound Care (New Rochelle)"},{"issue":"01","key":"ref20","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1089\/lrb.2016.0015","article-title":"Animal models of secondary lymphedema: New approaches in the search for therapeutic options","volume":"15","author":"R Hadrian","year":"2017","journal-title":"Lymphat Res Biol"},{"issue":"04","key":"ref21","doi-asserted-by":"crossref","first-page":"e70009","DOI":"10.1111\/micc.70009","article-title":"Clinical relevance of animal models of lymphatic dysfunction and lymphedema","volume":"32","author":"P S Podder","year":"2025","journal-title":"Microcirculation"},{"issue":"12","key":"ref22","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1161\/CIRCRESAHA.121.318307","article-title":"Advances in lymphedema","volume":"128","author":"S G Rockson","year":"2021","journal-title":"Circ Res"},{"issue":"08","key":"ref23","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.3390\/cancers12082297","article-title":"Lymphatic valves and lymph flow in cancer-related lymphedema","volume":"12","author":"D Iyer","year":"2020","journal-title":"Cancers (Basel)"},{"issue":"01","key":"ref24","doi-asserted-by":"crossref","first-page":"5397","DOI":"10.1038\/s41598-023-32473-z","article-title":"Recellularized lymph node scaffolds with human adipose-derived stem cells enhance lymph node regeneration to improve lymphedema","volume":"13","author":"H J Kang","year":"2023","journal-title":"Sci Rep"},{"issue":"05","key":"ref25","doi-asserted-by":"crossref","first-page":"e31205","DOI":"10.1002\/micr.31205","article-title":"Pedicled SCIP-based vascularized lymph node and lymphatic vessels transfer (VLNT and VLVT) for deep lymphatic system reconstruction and dead space obliteration after medial thigh sarcoma resection: A case report","volume":"44","author":"F Martini","year":"2024","journal-title":"Microsurgery"}],"container-title":["Journal of Reconstructive Microsurgery"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2687-0506.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T22:40:42Z","timestamp":1781649642000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2687-0506"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,21]]},"references-count":25,"journal-issue":{"issue":"06","published-online":{"date-parts":[[2026,6,16]]},"published-print":{"date-parts":[[2026,7]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2687-0506","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0743-684X","1098-8947"],"issn-type":[{"value":"0743-684X","type":"print"},{"value":"1098-8947","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,8,21]]},"published":{"date-parts":[[2025,8,21]]}}}