{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T19:36:44Z","timestamp":1792870604346,"version":"4.5.0"},"reference-count":32,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Beijing Northernland Biotechnology Co., Ltd"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"abstract":"<jats:p>\n                    This study was based on the multicenter, double-blind, randomized phase III HOPE CLTI-2 trial. An exploratory\n                    <jats:italic toggle=\"yes\">post hoc<\/jats:italic>\n                    analysis was performed to investigate the association between intramuscular injection site and ulcer healing outcomes in patients with chronic limb-threatening ischemia (CLTI) treated with recombinant human hepatocyte growth factor (rh-HGF), and to explore factors associated with ulcer healing. The analysis included 108 patients with CLTI treated with rh-HGF, comprising 184 ischemic lower-limb ulcers. Patients were classified according to injection site into a single-segment group, with injections limited to the calf muscles, and a multi-segment group, with injections administered to both the thigh and calf muscles. Outcomes included ulcer healing rate, time to ulcer healing, ankle-brachial index (ABI), Rutherford category, Wound, Ischemia, and foot Infection (WIfI) classification, and adverse clinical events. At the study endpoint, the unadjusted ulcer healing rate was significantly higher in the single-segment group than in the multi-segment group (75.0% vs. 57.1%,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.014), and the observed time to ulcer healing was shorter (153.00 [91.00\u2013184.00] days vs. 181.00 [94.00\u2013191.00] days,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.022). No significant between-group differences were observed in changes in ABI (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.290) or in WIfI classification (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.407). However, the distribution of Rutherford categories at study endpoint favored the single-segment group (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.016). In the multivariable logistic regression analysis, baseline ulcer area (odds ratio [OR]: 0.684, 95% confidence interval [CI]: 0.519\u20130.901,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.007) and male sex (OR: 3.924, 95% CI: 1.164\u201313.232,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.028) were independently associated with ulcer healing. Although the unadjusted comparisons favored the single-segment group, injection site was not independently associated with ulcer healing after multivariable adjustment (OR: 1.560, 95% CI: 0.703\u20133.460,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.269). Therefore, these findings should be considered hypothesis-generating. Whether a more anatomically targeted rh-HGF injection strategy under a fixed-dose regimen can improve ulcer healing requires evaluation in prospectively designed studies.\n                  <\/jats:p>","DOI":"10.1177\/10430342261498529","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:52:31Z","timestamp":1792666351000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association Between Intramuscular Injection Site and Ulcer Healing in Patients with Chronic Limb-Threatening Ischemia Treated with Recombinant Human Hepatocyte Growth Factor Naked Plasmid: A\n                    <i>Post Hoc<\/i>\n                    Analysis of the HOPE CLTI-2 Trial"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4176-2565","authenticated-orcid":false,"given":"Peng","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Vascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhuo","family":"Lian","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Rong","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengshi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jincan","family":"Liu","sequence":"additional","affiliation":[{"name":"Research and Development Center, Beijing Northland Biotechnology Company, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxiu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Research and Development Center, Beijing Northland Biotechnology Company, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changwei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Di","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leng","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehae179"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2019.02.016"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(19)30255-4"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2014.03.290"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2007.11.005"},{"issue":"6","key":"e_1_3_3_7_1","first-page":"A141","article-title":"The incidence and health economic burden of ischemic amputation in Minnesota, 2005\u20132008","volume":"8","author":"Peacock JM","year":"2011","unstructured":"6.Peacock JM, , Keo HH, , Duval S, et al. 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