{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:01:43Z","timestamp":1792652503410,"version":"4.5.0"},"reference-count":39,"publisher":"BMJ","issue":"4","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2019,1,28]]},"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Chou-Ling-Dan (CLD) (\n                      <jats:italic>Laggerapterodonta<\/jats:italic>\n                      ) granules are an ethnic herbal medicine from Yunnan province of China. CLD granules have been used for the treatment of inflammatory conditions and feverish diseases in China, including seasonal influenza, but few evidence-based medicine (EBM) clinical studies have been conducted to assess its efficacy and safety in the treatment of influenza. Here, we performed an EBM clinical trial combining Western Chinese medicine and traditional Chinese medicine (TCM) evaluation systems to evaluate the efficacy and safety of CLD granules in the treatment of seasonal influenza.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>The study is designed as a multicentre, randomised, double-blinded, double-simulation, oseltamivir-controlled and placebo-controlled, parallel-design clinical trial. Eligible subjects (n=318) will be allocated after satisfying the criteria (Western medicine). Subjects will be randomised to receive CLD granules, oseltamivir, or a placebo for 5 days of treatment and with follow-up after treatment to record symptoms and signs and to collect pharyngeal\/throat swabs and serum samples for detecting the virus and antibodies. At the same time, the syndrome differentiation criteria of TCM, such as tongue body, furred tongue and type of pulse, will be recorded as determined by doctors of both Western and Chinese medicine. Participants will be instructed to comply with the protocol and to keep a daily record of symptoms. The primary and secondary outcomes and safety indicators will be used to evaluate the efficacy and safety of CLD granules in the treatment of seasonal influenza based on both Western Chinese medicine and TCM evaluation systems.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The CLD granules clinical trial will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice and has been approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University. All participants must provide written informed consent. The results obtained will be disseminated at international medical conferences and in peer-reviewed publications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>NCT02662426; Pre-results.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2018-024800","type":"journal-article","created":{"date-parts":[[2019,4,3]],"date-time":"2019-04-03T07:30:09Z","timestamp":1554276609000},"page":"e024800","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Efficacy and safety of Chou-Ling-Dan granules in the treatment of seasonal influenza via combining Western and traditional Chinese medicine: protocol for a multicentre, randomised controlled clinical trial"],"prefix":"10.1136","volume":"9","author":[{"given":"Jiayang","family":"He","sequence":"first","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China"},{"name":"Tropical Medicine Institute, Guangzhou University of Chinese Medicine, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengtu","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyi","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenda","family":"Guan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxia","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi feng","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhua","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China"},{"name":"State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou Medical University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2019,4,2]]},"reference":[{"key":"2025121514593550000_9.4.e024800.1","doi-asserted-by":"crossref","first-page":"735","DOI":"10.3934\/mbe.2017041","article-title":"\"Effect of the epidemiological heterogeneity on the outbreak outcomes.\"","volume":"14.3","author":"Macacu","year":"2017","journal-title":"Mathematical Biosciences & Engineering"},{"key":"2025121514593550000_9.4.e024800.2","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.ccm.2016.11.005","article-title":"\"Pandemic and Avian Influenza A Viruses in Humans: Epidemiology, Virology, Clinical Characteristics, and Treatment Strategy.\"","volume":"38.1","author":"Li","year":"2017","journal-title":"Clinics in Chest Medicine"},{"key":"2025121514593550000_9.4.e024800.3","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1111\/tbed.12327","article-title":"A Systematic Review of the Comparative Epidemiology of Avian and Human Influenza A H5N1 and H7N9 - 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Beijing: China Medical Science Press, 2015."},{"key":"2025121514593550000_9.4.e024800.38","first-page":"63","article-title":"Therapeutic effect of Choulingdan mixture in the treatment of acute tonsillitis in children","volume":"29.12","author":"Wang","year":"2013","journal-title":"Hunan J Tradit Chin Med"},{"key":"2025121514593550000_9.4.e024800.39","doi-asserted-by":"publisher","DOI":"10.1097\/00006454-200102000-00002"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2018-024800","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T22:59:46Z","timestamp":1765839586000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2018-024800"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4]]},"references-count":39,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,4,2]]},"published-print":{"date-parts":[[2019,4]]}},"alternative-id":["10.1136\/bmjopen-2018-024800"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2018-024800","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4]]}}}