{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:23:14Z","timestamp":1787836994383,"version":"build-2784847793"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007937","name":"Peking University","doi-asserted-by":"publisher","award":["BMU2022TSXK001"],"award-info":[{"award-number":["BMU2022TSXK001"]}],"id":[{"id":"10.13039\/501100007937","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microcirculation"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Limb frostbite caused by cold exposure is a prevalent injury in winter. However, effective therapies remain limited, particularly for cold\u2010induced edema. This study evaluated the therapeutic potential of DangGuiSiNi Decoction (DSD), QiShenYiQi Pills (QSYQ), and their combination in a rat model of cold\u2010induced limb injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male Sprague\u2013Dawley rats (180\u2013220\u2009g) were subjected to hind limb frostbite through 5\u2010min dry ice exposure. Animals were administered with DSD, QSYQ, or their combination via oral gavage either 2\u2009h pre\u2010exposure or 5\u2009min post\u2010exposure, followed by daily dosing for 7\u2009days. Hennepin Score, hind limb blood flow, FITC\u2010albumin extravasation, rhodamine 6G\u2010labeled leukocyte adhesion, expression of tight\/adhesion junction proteins and basement membrane components, transient receptor potential (TRP) channel proteins, ATP content, and norepinephrine levels at 2\u2009h, 24\u2009h, and 7\u2009days post\u2010exposure were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The combination of DSD and QSYQ significantly alleviated frostbite\u2010induced edema and gangrene. Compared with control group, cold exposure increased the expression of TRPA1, TRPM8, RhoA, ROCK, p\u2010MLC, adrenergic receptor \u03b12c and norepinephrine content, while decreased the expression of tight and adherent junction proteins claudin\u20105, ZO\u20101, JAM\u20101, basement membrane proteins laminin and collagen\u2010IV, ATP content, and the activity of mitochondrial complex I, II, IV and V. DSD primarily counteracted the cold\u2010sensing and vasoconstrictive pathways by reducing TRPA1\/TRPM8 expression, norepinephrine levels, and RhoA\/ROCK activation, thereby improving blood flow. In contrast, QSYQ enhanced vascular barrier integrity by upregulating junction and basement membrane proteins, and boosted energy supply by increasing ATP content and mitochondrial complex activities. The combination of DSD and QSYQ produced aggregated therapeutic effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>DSD attenuates frostbite by inhibiting temperature\u2010sensing and vasoconstrictive pathways to ameliorate ischemia, whereas QSYQ protects vascular barrier function and mitigates edema by restoring energy metabolism. Their combination exhibits complementary and synergistic effects, supporting its use as a promising adjunctive therapy for cold\u2010induced injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/micc.70081","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T20:56:32Z","timestamp":1787691392000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>DangGuiSiNi<\/scp>\n                    Decoction and\n                    <scp>QiShenYiQi<\/scp>\n                    Pills Ameliorate Hyperpermeability and Edema Induced by Cold Exposure"],"prefix":"10.1111","volume":"33","author":[{"given":"Huan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences Peking University  Beijing China"},{"name":"Tasly Microcirculation Research Center, Peking University Health Science Center  Beijing China"},{"name":"Academy of Integration of Chinese and Western Medicine Peking University Health Science Center  Beijing China"},{"name":"The Key Discipline for Integration of Chinese and Western Basic Medicine (Microcirculation) of the National Administration of Traditional Chinese Medicine  Beijing China"},{"name":"Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan\u2010Kai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences Peking University  Beijing China"},{"name":"Tasly Microcirculation Research Center, Peking University Health Science Center  Beijing China"},{"name":"Academy of Integration of Chinese and Western Medicine Peking University Health Science Center  Beijing China"},{"name":"The Key Discipline for 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Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding\u2010Zhou","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences Peking University  Beijing China"},{"name":"Tasly Microcirculation Research Center, Peking University Health Science Center  Beijing China"},{"name":"Academy of Integration of Chinese and Western Medicine Peking University Health Science Center  Beijing China"},{"name":"The Key Discipline for Integration of Chinese and Western Basic Medicine (Microcirculation) of the National Administration of Traditional Chinese Medicine  Beijing China"},{"name":"Key Laboratory of Stasis and Phlegm, State Administration of Traditional Chinese Medicine of the People's Republic of China  Beijing 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