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Tuina, a traditional manual therapy in Chinese medicine, has been increasingly applied for fatigue-related conditions, yet high-quality clinical evidence remains scarce. This study aimed to evaluate the efficacy and safety of Tuina combined with usual care (UC) in adults with CFS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This assessor-blinded, single-center randomized clinical trial was conducted from April 10, 2024, to January 10, 2025, at Shuguang Hospital, Shanghai University of Traditional Chinese Medicine. A total of 110 participants meeting the 1994 US Centers for Disease Control and Prevention diagnostic criteria for CFS were randomly assigned (1:1) to receive Tuina plus UC or UC alone. The Tuina group received three 20-minute sessions per week for 4\u2009weeks (12 sessions in total) in addition to UC, which included health education, lifestyle guidance, and individualized symptom-targeted treatments but excluded Tuina therapy. The primary outcome was fatigue severity at 4\u2009weeks measured by the 11-item Chalder Fatigue Questionnaire (CFQ-11). Secondary outcomes included anxiety and depression (Hospital Anxiety and Depression Scale), sleep quality (Pittsburgh Sleep Quality Index), and physical functioning and bodily pain (Short Form-36 subscales). Data were analyzed using analysis of covariance with baseline scores as covariates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Baseline characteristics were comparable between groups. At week 4, compared with UC alone, Tuina plus UC led to greater improvement in fatigue (CFQ total score: adjusted mean difference \u22122.90 [95% CI \u22124.69 to \u22121.12];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002; effect size 0.62), and more participants achieved the minimal clinically important difference in CFQ total score (89.1% vs 69.1%;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). Benefits also favoured Tuina for physical fatigue (\u22122.21 [95% CI \u22123.40 to \u22121.02];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001; effect size 0.70), whereas the effect on mental fatigue was smaller (\u22120.79 [95% CI \u22121.52 to \u22120.06];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03; effect size 0.41). Tuina further reduced anxiety (\u22121.79 [95% CI \u22122.92 to \u22120.65];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002) and improved overall sleep quality (PSQI total score: \u22121.62 [95% CI \u22122.60 to \u22120.65];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0013); among PSQI subscales, only sleep duration remained statistically significant after Bonferroni correction. Other secondary outcomes did not differ significantly between groups, and no serious adverse events occurred.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Tuina combined with UC produced clinically meaningful improvements in overall fatigue and significant improvements in physical fatigue compared with UC alone, with additional benefits in anxiety and overall sleep quality, and was safe and well tolerated. These findings suggest that Tuina may be a promising adjunctive therapy for CFS and warrant confirmation in larger multicenter trials with longer-term follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      International Traditional Medicine Clinical Trial Registry, ITMCTR2025000002. Registered 1 January 2025 \u2013 Retrospectively registered,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/itmctr.ccebtcm.org.cn\/mgt\/project\/view\/-5709466987144715200\" ext-link-type=\"uri\">https:\/\/itmctr.ccebtcm.org.cn\/mgt\/project\/view\/-5709466987144715200<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-025-07624-7","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T14:49:54Z","timestamp":1767883794000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tuina therapy for patients with chronic fatigue syndrome: a randomized controlled trial"],"prefix":"10.1186","volume":"24","author":[{"given":"Shoujian","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sitong","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianxiang","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanda","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6854-4202","authenticated-orcid":false,"given":"Lingjun","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"issue":"12","key":"7624_CR1","doi-asserted-by":"publisher","first-page":"953","DOI":"10.7326\/0003-4819-121-12-199412150-00009","volume":"121","author":"K Fukuda","year":"1994","unstructured":"Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. 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