ABSTRACT Objective Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a debilitating condition characterized by persistent fatigue, impaired functioning, and substantial societal burden. Although cognitive behavioral therapy (CBT) is commonly used for CFS/ME, the effective components and delivery formats remain unclear. Methods We systematically searched MEDLINE, Embase, PsyclNFO, Web of Science, the Cochrane Library, and major English and Chinese databases from inception to January 15, 2025, without language restrictions. Ultimately, a frequentist network meta‐analysis (NMA) and component network meta‐analysis (cNMA) of 16 randomized controlled trials were conducted to assess the associations between CBT components, delivery formats, and patient‐important outcomes. Results At the treatment level, guided self‐help CBT (mean difference [MD], −6.89; 95% CI, −9.56 to −4.22; moderate certainty) and individual CBT (MD, −4.81; 95% CI, −6.98 to −2.65; moderate certainty) probably reduced fatigue when measured immediately after treatment. At the component level, goal setting (incremental mean difference [iMD], −8.83; 95% CI, −16.92 to −0.74), third‐wave components (iMD, −6.02; 95% CI, −11.33 to −0.72), and cognitive restructuring (iMD, −4.41; 95% CI, −8.83 to 0.01) were associated with reduced fatigue when measured immediately after treatment. Psychoeducation was potentially counterproductive (iMD, 5.23; 95% CI, 0.64 to 9.82). At the end of follow‐up, cognitive restructuring was associated with reduced fatigue and depression, and improved physical function; goal setting was also associated with improved physical function. The combination of goal setting, third‐wave components, and cognitive restructuring delivered via guided self‐help may be an efficacious component‐based intervention relative to the nonspecific treatment component (iMD, −16.33; 95% CI, −26.68 to −5.99). Conclusions The effective CBT combination probably involves goal setting, third‐wave components, and cognitive restructuring delivered via guided self‐help, while psychoeducation may be detrimental. Future studies should prospectively examine core CBT components and their interactions, as well as incorporate measures of dose and intensity to guide more personalized and scalable interventions. Trial Registration CRD420251018083

Background:While meta-analyses of randomised controlled trials have demonstrated the therapeutic effects of physical activity (PA) on insomnia, the real-world associations between different levels and domains of PA and insomnia symptoms remain unclear. We aimed to examine these associations in the general population. Methods:We conducted a systematic review and meta-analysis of observational studies. We searched PubMed, MEDLINE, EMBASE, APA PsycINFO, CINAHL, and the Cochrane Library up to 5 August 2024, including studies that examined the association between PA and insomnia symptoms in the general population. We calculated pooled effect sizes using a random-effects model and performed subgroup analyses by PA intensity and domain. We assessed publication bias using funnel plots. Results:We included 27 risk estimates. Compared with low PA, high PA was not significantly associated with insomnia risk (odds ratio (OR) = 0.96; 95% confidence interval (CI) = 0.85-1.09). Moderate PA was associated with a 7% lower risk of insomnia (OR = 0.93; 95% CI = 0.87-1.00). Subgroup analyses showed significant variation across activity domains, with occupational PA associated with a 21% higher risk of insomnia (OR = 1.21; 95% CI = 1.02-1.43). There was no evidence of publication bias. Conclusions:Moderate levels of PA are associated with a modest reduction in insomnia risk, whereas occupational PA may increase the risk. These findings highlight the importance of considering both the intensity and domain of PA in relation to sleep health. Registration:PROSPERO: CRD42023417826.

IntroductionNon-pharmacological therapies in traditional Chinese medicine (TCM) play an important role in the management of nonspecific chronic neck pain (NCNP). Tuina therapy and Baduanjin exercise, representing passive and active modalities, respectively, have shown benefits in reducing pain, improving cervical mobility, and enhancing quality of life. However, the therapeutic efficacy of Tuina combined with Baduanjin (TCB) approach for NCNP remains insufficiently elucidated. This study aims to determine whether TCB provides superior effects in pain relief and functional outcomes compared with Baduanjin exercise alone.Methods and analysisA total of 110 NCNP patients aged 18 to 50 years will be recruited. Participants will be randomly assigned in a 1:1 ratio to either the TCB group or Baduanjin group. Each group will undergo a total of 16 sessions of therapy over 8 weeks, with two sessions per week. Outcomes will be assessed at week 8, 20, and 32 post-randomization. The primary outcome is the pain intensity at week 8, assessed by the visual analogue scale scores (VAS). Secondary outcomes include functional disability (evaluated with the Neck Disability Index), quality of life (assessed using the 12-item Short Form Survey questionnaire), emotional distress (measured by the Hospital Anxiety and Depression Scale), sleep quality (evaluated with the Pittsburgh Sleep Quality Index), work efficiency (assessed using the Work Productivity and Activity Impairment Questionnaire-Specific Health Problem), and safety. The statistical analyses will follow the two-way repeated measures analysis of variance to compare clinical data between groups across different time points.Ethics and disseminationThe study protocol has received approval from the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine (2023-143). All study participants will be required to provide written informed consent. The findings of the study will be submitted to a peer-reviewed journal for publication and presented at scientific conferences. Additionally, the participants will receive copies of the results upon requests.Clinical Trial Registration: https://www.chictr.org.cn/, identifier (ChiCTR2300073680).

OBJECTIVE:This study aimed to investigate the differences in brain network connectivity between short-term and long-term chronic low back pain (CLBP) patients. METHODS:This retrospective study included 25 CLBP patients who underwent 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance (18F-FDG-PET/MR) imaging between January 2017 and December 2019. This imaging modality, which integrates functional and metabolic data, was used to assess both neural activity and metabolic alterations associated with CLBP. The connectivity between 14 large-scale brain networks (including pain processing, emotional regulation, and cognitive control networks) was analyzed, with pairwise correlations calculated for each participant. Significant differences between short-term and long-term CLBP patients were assessed using permutation testing with false discovery rate (FDR) correction. RESULTS:Metabolic connectivity analysis revealed significant differences between short-term and long-term CLBP patients, particularly in the connectivity between the left executive control network (LECN) and visual networks, salience and posterior salience networks (SN/pSN), and posterior salience and ventral default mode network (vDMN) (FDR corrected, p < 0.05). Additionally, a positive correlation was found between disease duration and connectivity in the salience, posterior salience, and vDMN networks, with longer disease duration associated with stronger connectivity. CONCLUSION:This study demonstrates that chronicity in CLBP is associated with altered brain network connectivity, particularly in networks related to emotional processing and pain perception. These findings highlight the neuroplastic changes that may occur with prolonged pain, providing insights into the underlying mechanisms of CLBP and potential targets for therapeutic intervention.

To determine how traditional Chinese manual therapy (Tuina) alleviates neuropathic pain (NPP) via central neuroplasticity. NPP was induced by chronic compression of the dorsal root ganglion (CCD) in male rats. From post-operative day 4 to day 28, Tuina (5 N, 2 Hz, 10 min/day) was applied at Weizhong acupoint (BL40). Behavioural tests (mechanical withdrawal threshold, MWT; paw withdrawal thermal latency, PWL) were performed on 2 and 1 day before CCD surgery and post-operative day 3, 7, 14, 21 and 28. Resting-state functional MRI was performed before CCD surgery and on postoperative days 7 and 28. CCD surgery induced persistent mechanical and thermal allodynia. Tuina reversed these deficits from day 14 onward. Compared with Sham group, the CCD group exhibited elevated regional homogeneity (ReHo) in the hippocampus, amygdala, brainstem and cerebellum. Tuina further increased ReHo in the amygdala, hippocampus, corpus callosum and temporal lobe between days 7 and 28. ReHo values in pain-related regions negatively correlated with MWT and PWL. Tuina may gradually relieve neuropathic pain by reshaping limbic and sensory-motor networks, offering a neuroplasticity-based rationale for its clinical use.

Chronic fatigue syndrome (CFS) is an often overlooked and debilitating multisystem disorder. Furthermore, the risk factors and pathophysiology of this disease remain unknown. This study aimed to assess risk factors for CFS by investigating the relationships between fatigue, sleep quality, and gastrointestinal symptoms in CFS patients, and to explore the possible pathophysiology of CFS. This is a prospective study conducted at the Health Check-up Center of Shanghai Shuguang Hospital. A total of 1,821 participants were included, with 956 in the case group and 865 in the control group. We performed a multidimensional assessment by evaluating various clinical symptoms, including multidimensional fatigue, insomnia, and gastrointestinal discomfort. Multivariable logistic regression was used to assess risk factors for CFS, including general biological, lifestyle, psychological, and social factors. An MFI-20 assessment revealed that the CFS group reported all aspects of fatigue twice as severe as those of the HC group, including more severe general fatigue [13.12 (12.95–13.30) vs 8.76 (8.55–8.96)], physical fatigue [12.91 (12.70–13.13) vs 7.94 (7.73–8.14)], reduced activity [12.88 (12.65–13.11) vs 7.71 (7.51–7.91)], reduced motivation [12.75 (12.52–12.97) vs 7.86 (7.65–8.07)], and mental fatigue [12.78 (12.56–13.00) vs 7.82 (7.62–8.02)] (p-values all <0.001). Compared with the HC group, the CFS group, CFS with insomnia group, and CFS with insomnia and gastrointestinal discomfort group showed increased scores in the MFI-20, PSQI, and GSRS. Participants who were male (adjusted OR [aOR]=1.579; 95

中医传统手法临床应用源远流长,是中医外治法体系中兼具理论内涵、技术特点与临床价值的闭环系统.《黄帝内经》即有按摩、按跷、按抚等手法记载,以及"按之则热气至,热气至则痛止""按之快然"等诸多手法作用论述,清晰界定了运用手法临床干预的"外治内应"作用属性.

This study aimed to evaluate the clinical efficacy and safety of Compound Ciwujia Granules in patients with chronic fatigue syndrome with syndrome of deficiency of both heart and spleen. It adopted a multicenter, double-blind, double-dummy, randomized controlled trial design and represented a pre-specified subgroup analysis regarding syndrome of deficiency of both heart and spleen from a registered clinical trial. A total of 224 patients with chronic fatigue syndrome with syndrome of deficiency of both heart and spleen were randomized, among whom 222 were included in the full analysis set(FAS). Patients were assigned in a 1∶1 ratio to the treatment group(Compound Ciwujia Granules + Guipi Granules placebo, 111 cases) and the control group(Guipi Granules + Compound Ciwujia Granules placebo, 111 cases), and the course of treatment lasted for 6 weeks. The primary outcome was the improvement rate measured in the Chalder Fatigue Questionnaire-11(CFQ-11) after 6 weeks of treatment. The secondary outcomes included the improvement rate after 3 weeks of treatment, changes in CFQ-11 scores from baseline, changes in CFQ-11 physical and mental fatigue scores from baseline, and changes in TCM syndrome(deficiency of both heart and spleen) scores from baseline after 3 and 6 weeks of treatment. Safety was assessed by recording adverse events. The results showed that 222 patients were included in the FAS, 203 in the per-protocol set(PPS), and 224 in the safety set(SS). In terms of primary outcome, FAS analysis showed that after 6 weeks of treatment, the improvement rate in CFQ-11 scores in experimental group was 73.99%(95%CI[69.10%, 78.87%]), compared to 52.87%(95%CI[47.99%, 57.76%]) in control group, with a between-group difference of 21.11%(95%CI[14.19%, 28.04%], P&lt;0.000 1). PPS analysis was consistent with FAS(difference of 20.54%, P&lt;0.000 1). After treatment for 6 weeks, the decrease in CFQ-11 scores was-13.81 in treatment group, significantly greater than-9.87 in control group(difference of-3.95, 95%CI[-5.23,-2.66], P&lt;0.000 1). Both physical fatigue and mental fatigue domain scores also favored the treatment group after 6 weeks of treatment(P&lt;0.000 1). The reduction in TCM syndrome scores after treatment for 6 weeks was also significantly greater in the treatment group than in the control group(FAS difference of-1.30, P=0.001 4; PPS difference of-1.14, P=0.005 3). No serious adverse events occurred in either group. In conclusion, Compound Ciwujia Granules significantly improved clinical symptoms in patients with chronic fatigue syndrome with syndrome of deficiency of both heart and spleen, demonstrating definite efficacy and good safety.

Background:Chronic neck pain (CNP) is a complex condition shaped by both peripheral tissue dysfunction and central nociplastic changes, including dysregulated endogenous pain modulation. Manual therapy (MT) is a guideline-endorsed intervention, but its mechanism of action remains debated. Moving beyond purely biomechanical accounts, we propose, as a working hypothesis rather than an established finding, that MT's clinical effects may be substantially mediated by neurophysiological modulation, particularly recruitment of descending inhibitory pathways. Mechanism:We synthesize contemporary evidence to propose that the "therapeutic soreness" some patients report during MT may indicate an afferent stimulus intensity sufficient to engage deep somatic Aδ and C-fiber input to the descending pain-modulatory system, centered on the Periaqueductal Gray (PAG)-Rostral Ventromedial Medulla (RVM) loop. We also review animal pharmacology implicating Locus Coeruleus (LC) noradrenergic and endocannabinoid signaling in shifting RVM output toward antinociceptive OFF-cell dominance; whether this specific chain operates during manual therapy in humans has not been directly tested. Perspective:We propose a conceptual, non-linear triphasic (Zone 1-2-3) dose-response framework as a hypothesis-generating tool, not a validated protocol. Subthreshold loading (Zone 1) is proposed to produce local tissue effects without engaging robust central modulation. An intermediate intensity (Zone 2), clinically associated with tolerable "therapeutic soreness", is hypothesized to engage descending inhibition through mechanisms that resemble, but are not equivalent to, Conditioned Pain Modulation (CPM-like effects). Loading beyond this window (Zone 3) is proposed to shift the balance toward central facilitation, potentially reinforcing rather than resolving the pain-tension cycle. Conclusion:This framework offers a testable, neurobiologically motivated rationale for individualizing MT dosing, particularly in sensitized phenotypes where the therapeutic window may be narrowed. It requires empirical validation, including objective sensorimotor and neuroimmune biomarkers, before it can inform clinical decision-making.

Adolescent idiopathic scoliosis (AIS) involves systemic bone-metabolic dysregulation and paraspinal microenvironment remodeling, but whether nutrition-related micronutrient-associated molecular programs overlap with these alterations remains unclear. Vitamin E (VE), comprising lipid-soluble tocopherols and tocotrienols, is linked to membrane protection, lipid peroxidation control, inflammatory mediator regulation, and endothelial responses. This study examined whether VE-related molecular signatures converge on AIS-associated redox, lipid-inflammatory, vascular, and multicellular remodeling programs. Peripheral blood miRNA data (GSE235203) and bone marrow transcriptomic data (GSE110359) were integrated using HERB-based compound mapping, VE-AIS shared-target enrichment, feature prioritization, intradisease GSEA, single-cell localization, CellChat analysis, and NHANES contextualization. HERB mapping generated a VE/tocopherol-related prioritization signal, not direct evidence of VE involvement in AIS. Forty-two shared VE-AIS targets were enriched mainly in oxidative stress, glutathione/peroxidase activity, and glutathione metabolism, with additional lipid-inflammatory and vascular signals. Five prioritized genes (SOD1, GCLC, PTGS1, PTGS2, and KDR) defined redox-buffering, lipid-inflammatory, and vascular-response axes. Single-cell and CellChat analyses localized these signatures mainly to endothelial, dendritic/APC-like, MSC-like, and stromal/osteogenic populations, suggesting a predicted concave-side enrichment of inflammatory-endothelial-stromal communication. Structural analyses supported the computational plausibility of α-tocopherol compatibility with selected proteins, particularly PTGS2. No AIS cohort with measured VE exposure or status was analyzed. NHANES provided external clinical nutrition context rather than AIS-specific validation. Overall, VE-related signatures overlapped with redox, lipid-inflammatory, vascular-response, and multicellular remodeling programs in AIS. These findings generate testable molecular hypotheses but do not show that VE intake, tocopherol status, or supplementation modifies AIS risk, severity, or progression.

Objective:To evaluate the therapeutic effects of manual therapy (MT) on pain, walking function, proprioception, and lower-limb muscle strength in geriatric patients with knee osteoarthritis (KOA), and to explore potential biomechanical mechanisms. Methods:In this prospective non-randomized controlled trial, 25 geriatric participants with unilateral mild-to-moderate KOA (intervention group) and 25 matched healthy controls were enrolled. The intervention group underwent a 4-week MT, while the control group received no intervention. The primary outcome was change in Western Ontario and McMaster Universities osteoarthritis index (WOMAC) pain subscale score. Secondary outcomes included 6-minute walk test (6-MWT) distance, proprioceptive force sense (PFS), and maximal isometric lower-limb strength. Causal mediation analysis was employed to investigate mechanistic pathways linking pain modulation to functional recovery. Results:Following MT intervention, the intervention group demonstrated significant reductions in WOMAC pain scores (13.04 ± 4.39 vs. 5.36 ± 2.40; P < 0.001), increased 6-MWT distance [320.44 m [95% CI: 283.68-357.20] vs. 612.28 m [95% CI: 594.42-630.14]; P < 0.001], and diminished inter limb asymmetry in PFS (54.52 ± 19.35 N vs. 15.92 ± 11.00 N; P < 0.05). Mediation analysis revealed that restoration of proprioceptive sensitivity accounted for 69.59% of the total effect through which pain reduction enhanced ambulatory capacity. Muscle strength profiling further indicated that functional improvement was potentially mediated by neuromuscular rebalancing of bilateral agonist-antagonist coordination. Conclusion:MT delivers significant short-term clinical benefits for elderly patients with unilateral mild-to-moderate KOA (Kellgren-Lawrence grades 0-2), including effective pain relief and improved walking ability, potentially through restoring proprioceptive sensitivity and modulating intermuscular balance.

BACKGROUND:Chronic nonspecific low back pain (CNLBP) is a major global driver of disability, with increasing attention toward individualized, evidence-based, and function-oriented interventions. To delineate the global CNLBP research landscape, we conducted a bibliometric and visualization analysis covering the period from 1996 to 2025. METHODS:Publications were retrieved from the Web of Science Core Collection, and VOSviewer, CiteSpace, and the R package bibliometrix were used to examine publication growth, author output, contributions by countries and institutions, journal influence, keyword co-occurrence patterns, and citation burst signals. RESULTS:A total of 937 peer-reviewed articles were identified, authored by 4,336 individuals across 288 journals and 65 countries. The largest share of publications was contributed by the United States, while Australia demonstrated strong international collaboration and citation impact. Institutions such as Vrije Universiteit Amsterdam, University of Southern Denmark, and University of Sydney played leading roles in CNLBP research output. Influential authors included Peter O'Sullivan and Kieran O'Sullivan, noted for contributions to psychosocial modeling and individualized rehabilitation. Keyword co-occurrence analysis identified four thematic clusters: (1) disease definition and epidemiology; (2) evidence-based management and health systems; (3) neuromechanical rehabilitation strategies; and (4) psychosocial dimensions and patient-centered outcomes. Burst keyword analysis revealed recent focus on "motor control" (2021-2024), "Tampa scale" (2023-2025), and "quality of life" (2023-2025), reflecting the shift toward precision rehabilitation and multidimensional assessment. CONCLUSIONS:A comprehensive overview of the evolving CNLBP research landscape was provided through this bibliometric analysis. Findings underscore the transition from diagnostic exploration to integrated clinical interventions, with growing emphasis on function, psychological well-being, and personalized care pathways.

Mechanotherapy, a form of mechanical loading (ML), effectively relieves tactile allodynia-associated neuropathic pain by targeting sensitization points stimulated by PIEZO2, a mechanosensitive ion channel. However, the molecular mechanisms underlying peripheral sensitization and ML-induced analgesia remain unclear. The study aimed to investigate the role of PIEZO2 in neuroinflammatory processes in a rat model of chronic compression injury (CCD) of dorsal root ganglia (DRG). Mechanical allodynia was assessed via paw withdrawal threshold in male Sprague–Dawley rats. ML was applied at intensities of 2.5–5 N, targeting either sensitization or non-sensitization points, with or without intrathecal administration of the PIEZO2 channel blocker D-GsMTx4. Behavioral assays, patch-clamp electrophysiology, western blot, enzyme-linked immunosorbent assay, RNA sequencing, and non-targeted metabolomics of skin, DRG, and spinal dorsal horn (SDH) were performed to evaluate neuronal excitability, inflammatory markers, and omics-level responses. CCD upregulates PIEZO2 expression in all tissues, indicating mechanical hypersensitivity and neuroinflammation. ML alleviates allodynia while suppressing SDH inflammation and MAPK signaling, especially at 5 N. Functionally blocking PIEZO2 attenuates ML-induced analgesia and downregulates rectifier K⁺ currents in DRG neurons. ML and the inhibition of PIEZO2 function exhibit similar lipid metabolism profiles and downregulate PGE₂ and all-trans-5,6-epoxyretinoic acid. PIEZO2 is essential for peripheral sensitization, as well as ML-induced analgesia, anti-inflammatory, and ion-channel-modulating effects, which may inform the development of novel non-pharmacological strategies.

Chronic pain management faces significant limitations due to adverse effects and insufficient long-term relief from existing therapies. Extracellular vesicles (EVs) are lipid bilayer-enclosed particles naturally carrying proteins, nucleic acids, and metabolites. Recently, EVs have emerged as a potential alternative approach. This review examines EVs from mesenchymal stem cells, neural cells, macrophages, and gut microbiota. EV activity is then assessed across the three major pain types defined by the ICD‑11: nociceptive pain, neuropathic pain, and nociplastic pain. We elucidate how source-specific EVs dynamically regulate different kinds of pain through multi-modal mechanisms, including neural signal transduction, neuroimmune axis coordination, structural neural repair, and metabolic network reprogramming. Furthermore, we discuss how these inherent therapeutic properties can be augmented through engineering approaches such as surface modification and cargo encapsulation, which enhance targeting and payload delivery. By integrating mechanistic insights into source‑specific EV functions with emerging engineering strategies, this review may provide a rational framework for developing next‑generation EV‑based analgesics. We conclude that harnessing the innate biological properties of EVs, complemented by strategic engineering, represents a potential non-opioid strategy for precise and effective management of chronic pain.

Objective Osteoarthritis (OA) is a leading cause of global disability, especially in aging populations. Comprehensive analyses of its long-term burden among adults aged ≥40 years are limited. This study aimed to assess global trends in OA burden from 1990 to 2021 to inform public health strategies. Methods This is a retrospective descriptive epidemiological study based on population-level aggregated public data. Using data from the Global Burden of Disease Study 2021, we estimated prevalence, incidence, and disability-adjusted life years (DALYs) for OA in adults aged ≥40 years. Age-standardized rates (ASRs) per 100,000 population were calculated. Joinpoint regression analysis was used to evaluate temporal trends. Analyses were stratified by age, sex, and socio-demographic index (SDI). Results In 2021, the global prevalence of OA among adults aged ≥40 years was 6,967.3 per 100,000, with a significant increase since 1990 (AAPC=0.278). The burden was consistently higher in females, with a prevalence 39% greater than in males. The most rapid increase occurred in the 55–59 age group (AAPC=0.356). High body mass index was a major associated factor, associated with approximately 32.7% of prevalent cases in 2021 (AAPC for attributed DALYs=1.108). While high-income Asia Pacific had the highest prevalence (8,608.6 per 100,000), the fastest growth was observed in Southeast Asia (AAPC=0.545) and low-middle SDI regions. Conclusion The global burden of OA continues to rise, with pronounced disparities by age, sex, and socioeconomic development. Our findings underscore the urgent need for early, targeted prevention strategies focusing on weight management and healthy aging to mitigate the future public health impact of OA.

Background:Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), is a debilitating condition characterized by persistent fatigue and a range of complex accompanying symptoms. While curative treatments remain limited, Tuina (a traditional manual therapy in Chinese medicine) has shown potential in alleviating fatigue in pilot studies. However, high-quality evidence from large-scale, multicenter trials regarding its efficacy and long-term sustainability is lacking. Objective:This trial aims to evaluate the efficacy and safety of Tuina combined with usual care (UC) for CFS compared with UC alone. Methods:This prospective, multicenter, randomized, open-label, assessor-blinded, parallel-group clinical trial will be conducted at 6 hospitals in China. The study consists of 3 phases: a 1-week run-in period, an 8-week treatment period, and a 24-week follow-up period. A total of 230 eligible participants diagnosed with CFS (Centers for Disease Control and Prevention 1994 criteria) will be recruited and randomly allocated (1:1) to receive either Tuina therapy plus UC (intervention group) or UC alone (control group). The intervention group will undergo 24 sessions of a standardized Tuina protocol over 8 weeks (3 sessions/week). Follow-up assessments will be conducted at weeks 4, 8, 20, and 32. The primary outcome is the change in fatigue severity measured by the 11-item Chalder Fatigue Questionnaire from baseline to week 8. Secondary outcomes include clinical response rate, sleep quality, anxiety, depression, quality of life, adverse events, and clinical global impression. Efficacy analysis will be performed using a mixed-effects model for repeated measures in the modified intention-to-treat population. Secondary outcomes will be analyzed as exploratory supportive end points using appropriate parametric or nonparametric tests based on data distribution, with week 8 defined as the main secondary time point and later follow-up visits interpreted as durability contrasts. Missing outcome data will be handled primarily through likelihood-based mixed-model estimation under a missing-at-random assumption, with multiple imputation and per-protocol analyses used as sensitivity analyses. Results:Recruitment for this trial will start in March 2026 and is expected to be completed by March 2027. The results of this study are expected to provide reliable evidence regarding the role of Tuina in the management of CFS. Conclusions:This multicenter randomized controlled trial will evaluate the effectiveness, long-term sustainability, and safety of Tuina therapy plus UC for improving fatigue, sleep, mood, and quality of life in CFS or ME. If proven beneficial, Tuina may serve as a scalable nonpharmacological option to support clinical decision-making and standardized implementation.

BackgroundChronic fatigue syndrome (CFS) is a disabling multisystem disorder characterized by persistent fatigue, post-exertional malaise, unrefreshing sleep, and neurocognitive and gastrointestinal symptoms. Effective non-pharmacological treatments remain limited. Increasing evidence suggests that CFS involves not only peripheral metabolic and gastrointestinal abnormalities but also central nervous system dysfunction. Altered tryptophan metabolism and gut-brain axis dysfunction may contribute to its pathophysiology. Tuina, a manual therapy used in traditional Chinese medicine, has been hypothesized to influence somatosensory, autonomic, stress-related, and gastrointestinal pathways. However, randomized controlled trials evaluating its clinical effects and exploratory gut-brain correlates in CFS remain scarce.MethodsThis multicenter, parallel-group, randomized controlled trial will enroll 166 participants with CFS, who will be allocated in a 1:1 ratio to a Tuina group or a standardized usual care group. The Tuina group will receive treatment twice weekly for 8 weeks, whereas the control group will receive standardized usual care consisting of health education and symptom-oriented management. The primary objective is to evaluate the effectiveness of Tuina on fatigue severity, assessed by the change in Fatigue Scale-14 (FS-14) score from baseline to week 8. Secondary outcomes include quality of life, sleep, pain, anxiety, depression, gastrointestinal symptoms, bowel function, and handgrip strength. Exploratory mechanistic outcomes include plasma tryptophan-pathway metabolites, gut microbiota profiling, resting-state functional magnetic resonance imaging, and magnetic resonance spectroscopy. Assessments will be conducted at baseline, weeks 4 and 8, and at 12 and 24 weeks after completion of treatment.DiscussionThis study is designed to evaluate the clinical effects of Tuina in CFS while exploring a biologically informed gut-brain framework involving tryptophan metabolism, gut microbiota, and brain network alterations. To our knowledge, few randomized trials in CFS have prospectively integrated clinical, metabolomic, microbiome, and multimodal neuroimaging measures within a single protocol. The findings may help clarify whether a non-pharmacological intervention can modulate interconnected peripheral and central pathways relevant to fatigue and related symptoms.Clinical trial registrationhttps://itmctr.ccebtcm.org.cn/mgt/project/view/1990257056896122880, Identifier ITMCTR2025002204.

Background:Tuina and exercise therapy are widely used to treat mechanical neck pain (MNP), but evidence on their combined efficacy remains limited. This study evaluated the effectiveness of Tuina combined with resistance exercise (RE) versus Tuina alone in managing MNP. Methods:We conducted a 4-week, analyst-blinded, randomized controlled trial with 90 participants with MNP. Participants were randomly assigned to receive either Tuina Therapy plus RE (TTRE, n = 45) or Tuina alone (n = 45). Both groups underwent two Tuina sessions per week for 4 weeks (eight sessions in total). In addition, the TTRE group performed RE three times daily for 4 weeks. Each RE consisted of 5 s of static resistance followed by 2 s of relaxation. The number of repetitions per session increased progressively: 5 in week 1, 10 in week 2, 15 in week 3, and 20 in week 4. The primary outcome was the change in pain visual analog scale (VAS) score from baseline to week 4. Secondary outcomes included the Neck Disability Index (NDI) score, peak strength of cervical muscle (PSCM), cervical range of motion (CROM), cervical curvature (Cobb Angle), and adverse events. Results:The mean age of the 90 enrolled patients was 26.4 years [standard deviation (SD), 3.1 and 49 (54.4%) were female]. The mean difference in VAS scores from baseline at week 4 for TTRE group was -4.2 (95% CI, -4.4 to -4.0). At week 4, the difference in VAS score was 0.5(95% CI, 0.30 to 0.77; p < 0.001) between Tuina group and TTRE group. Conclusion:In this study, participants with MNP in the TTRE group showed statistically greater improvements than those in the Tuina group in pain reduction, functional recovery, extension PSCM, and flexion CROM at week 4. TTRE may be considered a valuable option in the management of MNP. Clinical trial registration:We registered the trial with the Chinese Clinical Trial Registry (ChiCTR2300068344; Registration Date: February 15, 2023) at http://www.chictr.org.cn.

INTRODUCTION:The aim of this study was to evaluate the clinical efficacy of traditional Chinese acupoint massage (TCAM) combined with tailored tai chi on pain, disability, and selected quality-of-life domains in patients with lumbar disc herniation (LDH). METHODS:Seventy-two patients with LDH and low back pain (LBP) were randomly assigned to an intervention group (IG, TCAM + tailored tai chi, n = 36) or a control group (CG, TCAM alone, n = 36). Interventions were conducted 3 times per week for 4 weeks. The primary outcome was Oswestry Disability Index (ODI). Secondary outcomes included the visual analog scale (VAS, 0-10 points) and selected domains of the 36-Item Short Form Health Survey (SF-36). Baseline participant and therapist expectation scores were recorded, and sensitivity analyses were performed adjusting for these scores. ANCOVA adjusted for baseline outcome values, age, sex, and disease duration was used for between-group comparisons. Bonferroni correction was applied for SF-36 subscales. RESULTS:The primary outcome ODI decreased significantly more in the IG than in the CG (from 26.58 ± 7.79 to 9.67 ± 3.10 vs. 28.72 ± 9.25 to 15.69 ± 4.26; adjusted mean difference = 3.88, 95% CI: 0.50-7.27, p = 0.026). VAS scores improved on the 0-10 scale from 6.47 ± 1.47 to 2.21 ± 0.96 in the IG and from 6.71 ± 1.32 to 2.92 ± 0.99 in the CG, with an adjusted between-group difference of 0.47 (95% CI: 0.18-1.43, p = 0.012). Among SF-36 subscales, significant between-group differences after Bonferroni correction were observed in physical functioning, bodily pain, vitality, and mental health. Sensitivity analyses adjusting for expectation scores yielded consistent results. The total effective rate was 94.44% in the IG vs. 83.33% in the CG (p = 0.26). CONCLUSION:TCAM combined with tailored tai chi significantly improved functional disability, pain intensity, and selected quality-of-life domains compared with TCAM alone over 4 weeks. Sensitivity analyses suggest that these effects are robust and independent of baseline expectation scores. This multimodal physical therapy may be considered a complementary conservative treatment for patients with LBP due to LDH.