{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T10:43:21Z","timestamp":1782816201657,"version":"3.54.5"},"reference-count":34,"publisher":"Walter de Gruyter GmbH","issue":"6","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_jtim-2025-0043_s_013\">\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>Non-erosive reflux disease (NERD), a common gastrointestinal disorder, often responds poorly to acid suppressants. This study evaluated the efficacy and safety of Huoxue Tongjiang Decoction (HTD), a patented traditional Chinese medicine (TCM), for NERD with Qi stagnation-blood stasis syndrome, integrating network pharmacology and clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jtim-2025-0043_s_014\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Network pharmacology identified HTD's active components and targets using TCMSP and GeneCards databases. A \"drug-component-target\" network was constructed, followed by protein interaction analysis, Gene body analysis (GO), and KEGG pathway enrichment via DAVID. A randomized, double-blind, placebo-controlled trial enrolled 64 NERD patients with Qi stagnation-blood stasis syndrome, randomized to HTD (\n                      <jats:italic>n<\/jats:italic>\n                      = 32) or placebo (\n                      <jats:italic>n<\/jats:italic>\n                      = 32) for 4 weeks, with 2-week follow-up. Outcomes included reflux\/heartburn severity (Visual Analog Scale [VAS], gastroesophageal reflux disease questionnaire [GERD-Q]), TCM syndrome scores, SF-36 quality-of-life, HAD scores, and recurrence rates.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jtim-2025-0043_s_015\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Network analysis revealed 20 core HTD components (\n                      <jats:italic>e.g<\/jats:italic>\n                      ., quercetin, luteolin, baicalin) and 11 key targets (TNF, IL6, TP53), primarily modulating HIF-1 and TNF signaling pathways. Clinically, 30 HTD and 31 placebo patients completed the study. After 2\/4 weeks and follow-up, HTD showed significantly higher overall symptom remission (43.3%, 73.3%, 73.3%)\n                      <jats:italic>versus<\/jats:italic>\n                      placebo (16.1% at all timepoints;\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05). Reflux response rates for HTD were 30.0%, 66.7%, 66.7%\n                      <jats:italic>vs<\/jats:italic>\n                      . 12.9% (placebo;\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.0001). Heartburn response rates in HTD were 43.3%, 63.3%, 76.7%\n                      <jats:italic>vs<\/jats:italic>\n                      . 16.1% (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05). VAS reflux scores decreased from 3.75 \u00b1 1.599 to 1.98 \u00b1 1.292 (HTD)\n                      <jats:italic>vs<\/jats:italic>\n                      . minimal changes in placebo; heartburn scores improved similarly (3.33 \u00b1 1.724 to 1.81 \u00b1 1.471;\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05 post-2 weeks). GERD-Q scores were lower in HTD (7.9 \u00b1 2.29, 6.2 \u00b1 2.07, 6.8 \u00b1 2.40) . placebo (9.4 \u00b1 2.83, 8.9 \u00b1 2.55, 8.9 \u00b1 2.59;\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05). TCM syndrome improvement rates in HTD were 56.7%, 86.7%, 76.7%\n                      <jats:italic>vs<\/jats:italic>\n                      . 16.1%, 25.8%, 41.9% (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05). SF-36 physical pain, energy, and mental health scores improved in HTD (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05). Recurrence rates were 27.3% (HTD)\n                      <jats:italic>vs<\/jats:italic>\n                      . 40.0% (placebo;\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05). No adverse events occurred.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jtim-2025-0043_s_016\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HTD significantly alleviates reflux, heartburn, and retrosternal pain in NERD, improves quality of life, reduces recurrence, and demonstrates duration-dependent efficacy. Its anti-inflammatory mechanisms may involve TNF and HIF-1 pathways, with no safety concerns observed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/jtim-2025-0043","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T06:59:17Z","timestamp":1760597957000},"page":"582-598","source":"Crossref","is-referenced-by-count":2,"title":["Integrated network pharmacology and clinical study to reveal the efficacy and tolerability of Huoxue Tongjiang decoction for the treatment of non-erosive reflux disease-related symptoms"],"prefix":"10.1515","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1683-9356","authenticated-orcid":false,"given":"Yanping","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Tianjin Integrated Traditional Chinese and Western Medicine Hospital, Tianjin Nankai Hospital; Tianjin University , Tianjin , China"},{"name":"Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Integrated Traditional Chinese and Western Medicine Hospital, Tianjin Nankai Hospital; Tianjin University , Tianjin , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peicai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tianjin Integrated Traditional Chinese and Western Medicine Hospital, Tianjin Nankai Hospital; Tianjin University , Tianjin , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxia","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tianjin Integrated Traditional Chinese and Western Medicine Hospital, Tianjin Nankai Hospital; Tianjin University , Tianjin , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tianjin Integrated Traditional Chinese and Western Medicine Hospital, Tianjin Nankai Hospital; Tianjin University , Tianjin , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiannan","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tianjin Integrated Traditional Chinese and Western Medicine Hospital, Tianjin Nankai Hospital; Tianjin University , Tianjin , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Integrated Traditional Chinese and Western Medicine Hospital, Tianjin Nankai Hospital; Tianjin University , Tianjin , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"2025122216030780426_j_jtim-2025-0043_ref_001","unstructured":"Zhang BH, Zhou BD, Tang XD. 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