{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:41:33Z","timestamp":1792784493539,"version":"4.5.0"},"reference-count":19,"publisher":"Elsevier BV","issue":"12","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T00:00:00Z","timestamp":1607040000000},"content-version":"vor","delay-in-days":369,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Beijing Northland Biotech., Co., Ltd., China"}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1016\/j.ymthe.2019.10.017","type":"journal-article","created":{"date-parts":[[2019,11,3]],"date-time":"2019-11-03T03:27:35Z","timestamp":1572751655000},"page":"2158-2165","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":45,"title":["A Randomized, Double-Blind, Placebo-Controlled Phase II Study of Hepatocyte Growth Factor in the Treatment of Critical Limb Ischemia"],"prefix":"10.1016","volume":"27","author":[{"given":"Yongquan","family":"Gu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijun","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changjian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bi","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changwei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongbin","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Shu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuxian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengquan","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"Suppl S","key":"10.1016\/j.ymthe.2019.10.017_bib1","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1016\/j.jvs.2006.12.037","article-title":"Inter-society consensus for the management of peripheral arterial disease (TASC II)","volume":"45","author":"Norgren","year":"2007","journal-title":"J.\u00a0Vasc. Surg."},{"key":"10.1016\/j.ymthe.2019.10.017_bib2","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1185\/03007990802274379","article-title":"Management of peripheral arterial disease patients: comparing the ACC\/AHA and TASC-II guidelines","volume":"24","author":"Mohler","year":"2008","journal-title":"Curr. Med. Res. Opin."},{"key":"10.1016\/j.ymthe.2019.10.017_bib3","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/S0140-6736(13)61249-0","article-title":"Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis","volume":"382","author":"Fowkes","year":"2013","journal-title":"Lancet"},{"key":"10.1016\/j.ymthe.2019.10.017_bib4","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1001\/jamasurg.2016.2018","article-title":"The current state of critical limb ischemia: a systematic review","volume":"151","author":"Farber","year":"2016","journal-title":"JAMA Surg."},{"key":"10.1016\/j.ymthe.2019.10.017_bib5","unstructured":"Note for guidance on clinical investigation of medicinal products for the treatment\u00a0of\u00a0peripheral arterial occlusive disease. European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products (EMEA CPMP), April 25, 2002, CPMP\/EWP\/714\/98. https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/note-guidance-clinical-investigation-medicinal-products-treatment-peripheral-arterial-occlusive_en.pdf."},{"key":"10.1016\/j.ymthe.2019.10.017_bib6","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1097\/01.RVI.0000240426.53079.46","volume":"17","author":"Hirsch","year":"2006","journal-title":"J.\u00a0Vasc. Interv. Radiol."},{"key":"10.1016\/j.ymthe.2019.10.017_bib7","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1002\/jgm.1614","article-title":"A phase I clinical study of naked DNA expressing two isoforms of hepatocyte growth factor to treat patients with critical limb ischemia","volume":"13","author":"Gu","year":"2011","journal-title":"J.\u00a0Gene Med."},{"key":"10.1016\/j.ymthe.2019.10.017_bib8","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1006\/bbrc.1994.1523","article-title":"Hepatocyte growth factor and its variant with a deletion of five amino acids are distinguishable in their biological activity and tertiary structure","volume":"200","author":"Shima","year":"1994","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.ymthe.2019.10.017_bib9","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1038\/gt.2010.101","article-title":"Naked DNA expressing two isoforms of hepatocyte growth factor induces collateral artery augmentation in a rabbit model of limb ischemia","volume":"17","author":"Pyun","year":"2010","journal-title":"Gene Ther."},{"key":"10.1016\/j.ymthe.2019.10.017_bib10","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1002\/jgm.1603","article-title":"Enhanced cardioprotective effects by coexpression\u00a0of two isoforms of hepatocyte growth factor from naked plasmid\u00a0DNA in a rat ischemic heart disease model","volume":"13","author":"Hahn","year":"2011","journal-title":"J.\u00a0Gene Med."},{"key":"10.1016\/j.ymthe.2019.10.017_bib11","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1038\/gt.2011.21","article-title":"Safety of a non-viral plasmid-encoding dual isoforms of hepatocyte growth factor in critical limb ischemia patients: a phase I study","volume":"18","author":"Henry","year":"2011","journal-title":"Gene Ther."},{"key":"10.1016\/j.ymthe.2019.10.017_bib12","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1016\/j.jvs.2010.07.044","article-title":"Safety and efficacy of patient specific intramuscular injection of HGF plasmid gene therapy on limb perfusion and wound healing in patients with ischemic lower extremity ulceration: results of the HGF-0205 trial","volume":"52","author":"Powell","year":"2010","journal-title":"J.\u00a0Vasc. Surg."},{"key":"10.1016\/j.ymthe.2019.10.017_bib13","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1038\/gt.2010.51","article-title":"Randomized, double-blind, placebo-controlled clinical trial of hepatocyte growth factor plasmid for critical limb ischemia","volume":"17","author":"Shigematsu","year":"2010","journal-title":"Gene Ther."},{"key":"10.1016\/j.ymthe.2019.10.017_bib14","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/gt.2015.110","article-title":"Safety and efficacy of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with critical limb ischemia","volume":"23","author":"Kibbe","year":"2016","journal-title":"Gene Ther."},{"key":"10.1016\/j.ymthe.2019.10.017_bib15","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1038\/mt.2008.33","article-title":"Therapeutic angiogenesis with intramuscular NV1FGF improves amputation-free survival in patients with critical limb ischemia","volume":"16","author":"Nikol","year":"2008","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2019.10.017_bib16","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1016\/S0140-6736(11)60394-2","article-title":"Effect of fibroblast growth factor NV1FGF on amputation and death: a randomised placebo-controlled trial of gene therapy in critical limb ischaemia","volume":"377","author":"Belch","year":"2011","journal-title":"Lancet"},{"key":"10.1016\/j.ymthe.2019.10.017_bib17","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1161\/CIRCULATIONAHA.107.727347","article-title":"Results of a double-blind, placebo-controlled study to assess the safety of intramuscular injection of hepatocyte growth factor plasmid to improve limb perfusion in patients with critical limb ischemia","volume":"118","author":"Powell","year":"2008","journal-title":"Circulation"},{"key":"10.1016\/j.ymthe.2019.10.017_bib18","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1161\/01.HYP.0000136394.08900.ed","article-title":"Safety evaluation of clinical gene therapy using hepatocyte growth factor to treat peripheral arterial disease","volume":"44","author":"Morishita","year":"2004","journal-title":"Hypertension"},{"key":"10.1016\/j.ymthe.2019.10.017_bib19","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1586\/14779072.2014.955850","article-title":"Beperminogene perplasmid for the treatment of critical limb ischemia","volume":"12","author":"Suda","year":"2014","journal-title":"Expert Rev. Cardiovasc. Ther."}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001619304939?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001619304939?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T17:55:06Z","timestamp":1761501306000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001619304939"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12]]},"references-count":19,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["S1525001619304939"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2019.10.017","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2019,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A Randomized, Double-Blind, Placebo-Controlled Phase II Study of Hepatocyte Growth Factor in the Treatment of Critical Limb Ischemia","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2019.10.017","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2019.11.001","name":"associatedlink","label":"CrossRef DOI link to the associated document"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019","name":"copyright","label":"Copyright"}]}}