{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T04:18:05Z","timestamp":1777695485990,"version":"3.51.4"},"reference-count":54,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100007279","name":"Shanghai Municipal Health Bureau","doi-asserted-by":"publisher","award":["20214Y0177"],"award-info":[{"award-number":["20214Y0177"]}],"id":[{"id":"10.13039\/501100007279","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82104948"],"award-info":[{"award-number":["82104948"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82205213"],"award-info":[{"award-number":["82205213"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Integr Cancer Ther"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Lung cancer remains the leading cause of cancer-related morbidity and mortality all over the world, with high rates of locoregional recurrence and distant metastasis even after curative-intent surgical resection. The mechanisms of the tumor microenvironment\u2019s role in supporting metastasis through the formation of pre-metastatic niches are crucial areas of investigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Lung metastasis models were established by injecting Lewis lung cancer cells (LLCs) into the tail vein of 20 specific pathogen free (SPF)\u2014grade male C57BL\/6 mice. The mice were divided into 4 groups: control (physiological saline), GuBenPeiYuan (GBPY) medium-dose (25\u2009g\/kg), GBPY high-dose (50\u2009g\/kg), all administered by gavage, and gemcitabine (50\u2009mg\/kg, administered by intraperitoneal injection on days 1, 4, 7, 10, and 13), the total treatment duration was 14\u2009days. Qualitative and quantitative analyses of GBPY were performed using Ultra-Performance Liquid Chromatography (UPLC). Metastasis was observed using hematoxylin and eosin (H&amp;E) staining, and the expression of immune cells was assessed by flow cytometry and immunofluorescence staining. Mechanistic insights were gained through Western blot.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The high-dose GBPY and gemcitabine groups showed significantly fewer lung metastatic tumors (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.002;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&lt;\u2009.001), while no significant difference was observed between the medium-dose group and control group (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.438). Flow cytometry results indicated that high-dose GBPY significantly downregulated Myeloid-Derived Suppressor Cells (MDSCs) and G-MDSCs (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.002 and\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.001, respectively), upregulated dendritic cells (DCs;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.021), increased M1 macrophages (F4\/80\n                      <jats:sup>+<\/jats:sup>\n                      \/iNOS\n                      <jats:sup>+<\/jats:sup>\n                      ;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.001) and decreased M2 macrophages (CD206\n                      <jats:sup>+<\/jats:sup>\n                      F4\/80\n                      <jats:sup>+<\/jats:sup>\n                      ) (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&lt;\u2009.001). Furthermore, Western blot results showed that the high-dose GBPY group significantly inhibited the expression of p-JAK2, p-STAT3 (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.013,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u2009.001 respectively).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The GBPY Formula may reduce lung cancer metastasis and recurrence by inhibiting the JAK2\/STAT3 pathway, downregulating the presence of MDSCs, upregulating the proportion of DCs, and promoting the polarization of M2 macrophages to M1 macrophages. These changes enhance the anti-tumor immune response, contributing to the reduction of lung cancer metastasis and recurrence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15347354251324650","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T02:28:30Z","timestamp":1750818510000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["GuBenPeiYuan Formula Inhibits Lung Cancer Metastasis by Suppressing Myeloid-Derived Suppressor Cells and Related Immune Cells"],"prefix":"10.1177","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1361-4998","authenticated-orcid":false,"given":"Yizhao","family":"Du","sequence":"first","affiliation":[{"name":"Yueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Xu","sequence":"additional","affiliation":[{"name":"Yueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hailun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Yueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingwen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Yueyang Hospital of Integrated Traditional Chinese Medicine and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 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