Fascia is increasingly recognized as a dynamic functional system. It can actively sense, transmit, and regulate mechanical, sensory, and metabolic signals. Why does fascia play such a critical role in chronic pain and movement disorders? Researchers are now rethinking the pathophysiological mechanisms underlying this role. Previous systematic reviews have typically focused primarily on specific mechanisms or interventions. In contrast, this study takes a holistic view of fascial function. It integrates multiple physiological functions of the fascia: mechanical integration, sensory modulation, cellular and matrix remodeling, as well as metabolic and immune regulation. From the perspective of functional imbalance, we further explore the pathological mechanisms associated with the fascia. Building on this, we then focus on how to assess fascial function from multiple dimensions and on specific targeted interventions. For assessment, we have systematically compiled a set of multi-stage quantitative techniques. These include clinical palpation, ultrasound, and elastography, tissue mechanics testing, microdialysis, omics approaches, electrophysiological testing, and digital modeling. For interventions, we have listed a range of modulating approaches, such as manual therapy, exercise rehabilitation, dry needling and acupuncture, fascial injections, targeted drugs, and biotechnological materials derived from tissue engineering. This review summarizes a clinical decision-making framework guided by the assessment of fascial functional status. It emphasizes a systematic approach and links quantitative diagnosis with precise interventions. Additionally, it provides a literature synthesis for understanding fascial mechanisms and related disorders and offers a reference foundation for the field's transition from empirical treatment to measurable, reproducible, and individualized practice.

Neuroinflammation is a key immunological driver of spinal sensitization and the transition from acute to chronic pain. Although mechanical interventions can reduce pain, the immuno-inflammatory mechanisms linking mechanical cues to resolution of spinal neuroinflammation remain poorly integrated and inconsistently defined. A major gap is the lack of a mechanobiological framework that connects mechanotransduction with glial activation, cytokine/chemokine signaling, and neuroimmune synaptic plasticity, and translates these mechanisms into measurable biomarkers and reproducible protocols. Here, we synthesize preclinical and clinical evidence showing how mechanical stimuli may modulate neuroinflammation-driven sensitization. We summarize mechanotransduction pathways that shape microglial and astrocytic reactivity, inflammatory signaling, and downstream remodeling of ion channels, receptors, and synaptic circuits. We also discuss how mechanical interventions may shift the spinal inflammatory microenvironment by improving perfusion and metabolic homeostasis. Finally, we outline candidate biomarker panels and highlight key limitations, including heterogeneity in dosing, outcomes, and translational models. Overall, mechanical forces may act as immunomodulatory cues that reprogram neuroinflammation and weaken spinal sensitization, supporting a mechanistic basis for non-pharmacological analgesia. Future progress requires standardized mechanical dosing, mechanism-informed biomarkers, and rigorous translational pipelines to enable quantifiable, personalized mechanotherapy for chronic pain.

Between 50% and 80% of children diagnosed with Autism Spectrum Disorder (ASD) are estimated to experience sleep disturbances, highlighting the importance of exploring the role of the circadian clock in ASD development. Previous studies have identified a potential link between Bmal1 deficiency and ASD in mouse models. In this study, we first characterise the expression patterns of circadian proteins. Subsequent behavioural tests and western blot analyses revealed that mice exposed to valproic acid (VPA) displayed autistic-like behaviours, along with altered circadian protein expression and disruption in Wnt signalling protein levels. Further studies showed that Bmal1 knockout exacerbates these behavioural changes and further impaired Wnt signalling and downstream protein expression in VPA-exposed mice. Notably, treatment with the circadian biomarker melatonin reversed Wnt downregulation and improved the behaviour deficit in VPA-exposed mice. The therapeutic effect of melatonin appears to be mediated by its regulation of the Wnt/β-catenin signalling pathway, which is linked to Bmal1-mediated circadian dysfunction. Together, our findings provide experimental evidence supporting the role of circadian dysregulation in ASD pathogenesis, highlight the therapeutic potential of melatonin in VPA-exposed mice, and suggest that Bmal1 may act as a co-activator in the Wnt-β-catenin signalling pathway.

BackgroundChronic low back pain (CLBP) is often accompanied by anxiety and depression, which hinders clinical treatment. Therefore, this study conducts a Bayesian network meta-analysis to compare the effectiveness of different non-drug interventions in relieving pain and related emotional symptoms in CLBP patients.MethodsThis review was prospectively registered in PROSPERO (CRD420251066414). As of June 2025, PubMed, Embase, Cochrane Library, Web of Science, CINAHL, Scopus, CNKI, and Wanfang databases have been searched to collect randomized controlled trials concerning non-pharmacological interventions for CLBP. The main outcomes are pain, anxiety, and depression. The scoring directions of all outcome scales were consistent. To account for differences in measurement tools, effect sizes are expressed as standardized mean differences (SMD), estimated using a Bayesian random-effects model based on change scores, and reported with 95% credible intervals (CrIs), adjusted using Hedges' g. Comprehensive sensitivity analysis, subgroup analysis, and regression analysis were carried out to explore the source of heterogeneity and the factors affecting the treatment results.ResultsTwenty-four trials were ultimately included (n = 1828), involving 9 non-pharmacological interventions. The analysis of the results shows that mind-body exercises (MBE) demonstrated favorable effects for pain relief [SMD: −1.55, 95% CrI (−2.50, −0.59)] and depression and anxiety reduction [SMD: −1.14, 95% CrI (−1.74, −0.54), SMD: −1.38, 95% CrI (−1.95, −0.81)]. Structured exercise (SE) was also associated with relief in pain [SMD: −1.02, 95% CrI (−1.94, −0.09)], depression, and anxiety [SMD: −0.77, 95% CrI (−1.35, −0.19), SMD: −0.69, 95% CrI (−1.25, −0.14)]. Integrated rehabilitation therapy (IR) showed a potential benefit for improving depression [SMD: −0.74, 95% CrI (−1.28, −0.18)]. Considerable heterogeneity was observed across all outcome measures (pain: 86.24%; depression: 70.64%; anxiety: 66.08%). Additional subgroup interaction analyses did not identify any factors influencing treatment outcomes. Meta-regression suggested that the number of interventions may influence pain, whilst the type of intervention may influence anxiety.ConclusionMBE and SE may help alleviate pain, anxiety, and depression among CLBP individuals, whilst IR may have a modest beneficial impact on depression. Given the high heterogeneity across different outcome measures, these conclusions should be evaluated with caution, and further high-quality research is required to substantiate them.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251066414, PROSPERO, CRD420251066414.

BackgroundThis study investigated whether manual therapy applied to tendon organs ameliorated neuromuscular dysfunction in rats with spasticity induced by upper motor neuron injury associated with spastic cerebral palsy, and analyzed the potential involvement of the C-fiber-mediated CaMKII signaling pathway.MethodsMale rats were used to establish palsy models and divided into groups: Control, Model, Manual Therapy (MT), Capsaicin Treatment, Sham, CaMKII Inhibitor, and DMSO Solvent groups. Except for Control, all underwent pyramidal-tract destruction. After modeling, the MT group received manual therapy on the left-lower leg tendon organs. The Capsaicin group underwent sciatic nerve capsaicin treatment for C-fiber block on days 2 and 7; the Sham group had sciatic nerve exposure only. Both received daily manual therapy intervention for 14 days. The CaMKII Inhibitor and DMSO Solvent groups received intrathecal injections every 2 days (7 times total) without manual intervention. Spasticity-related behavioral indices, molecular expression, and neurotransmitter levels were assessed.ResultsManual therapy reduced the neurological deficit scores and muscle spasticity scores of model rats, improved the pathological morphology of the pyramidal tract and skeletal muscle, and regulated the expression of key molecules and neurotransmitters in the spinal cord and hippocampus. The therapeutic effects of manual therapy were significantly attenuated after C-fiber blockage, and although CaMKII inhibition could partially mimic the neuromodulatory effects of manual therapy, its efficacy in alleviating spasticity was inferior to that of manual-therapy intervention.ConclusionManual therapy appears to regulate CaMKII signaling via C-fiber afferent pathways to ameliorate neuromuscular dysfunction in a rat model of spasticity induced by pyramidal-tract lesion, thereby providing experimental evidence for the clinical application of optimized manual therapy parameters in the management of spasticity in patients with cerebral palsy.

To observe the effect of pressing manipulation on pain sensitization of spinal cord dorsal horn (SCDH) in rats with myofascial trigger points. Thirty-two male Sprague-Dawley rats were divided into a blank group (n=10) and a group for modeling (n=22) using the random number table method. Rats in the group for modeling were subjected to blunt blow plus centrifugal motion, and 20 rats successfully modeled were randomly divided into a model group and a pressing manipulation group, with 10 rats in each group. Rats in the blank group and the model group were reared routinely. Rats in the pressing manipulation group were subjected to pressing manipulation for 7.5 min continuously at 10 times/min, once every other day for a total of 7 times. After the values of pressure pain threshold (PPT) and soft tissue tension (STT) D0.2 were measured in each group, the histomorphological changes at trigger points were observed. The expression levels of vesicular glutamate transporter 1 (VGluT1), M1 microglia marker (CD86), and M2 microglia marker (CD206) in lumbar enlargement’s SCDH were detected by immunohistochemistry. Western blotting was used to observe the expression levels of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), N-methyl-D-aspartic acid receptor 2B (NR2B), phosphorylated nuclear factor-kappa B p65 subunit (p-p65), interleukin (IL)-6, and tumor necrosis factor (TNF)-α. Compared with the blank group, the values of PPT and STT D0.2 were significantly decreased (P<0.05), and the morphological structure of muscle cells was changed with different sizes; the nucleus moved inward, inflammatory cells infiltrated between cells, and fibroblasts were increased in the model group. Compared with the model group, the values of PPT and STT D0.2 were significantly higher (P<0.05), the morphological structure of muscle cells showed improvement, and the phenomena of nuclear migration, inflammatory cell infiltration, and fibroblast proliferation were all reduced in the pressing manipulation group. Compared with the blank group, the expression levels of VGluTl, CD86, p-ERK1/2, NR2B, IL-6, TNF-α, and p-p65 were significantly increased (P<0.05), and the expression level of CD206 was decreased (P<0.05) in the lumbar enlargement’s SCDH in the model group. Following pressing manipulation intervention, the expression levels of the aforementioned proteins were significantly reduced (P<0.05), while the expression level of CD206 was elevated (P<0.05) in the lumbar enlargement’s SCDH in the pressing manipulation group. The pressing manipulation in Tuina (Chinese therapeutic massage) may promote microglial polarization from M1 to M2 in lumbar enlargement’s SCDH in trigger point rats, reduce the release of inflammatory factors, and inhibit the activity of glutamate neurons and their synapses, thereby inhibiting pain sensitization and relieving pain.

Objective To investigate whether Tuina alleviates fibrotic symptoms in myofascial trigger points (MTrPs) by regulating transforming growth factor (TGF)-β1/Smad3 signaling pathway, thereby deactivating these points. Methods This study comprised two experimental phases. In phase 1, 27 specific pathogen-free (SPF) grade female Sprague-Dawley (SD) rats were randomized into three groups: control 1, model 1, and Tuina 1 groups. Model 1 and Tuina 1 groups underwent an 8-week MTrPs modeling protocol involving blunt impact and eccentric exercise. After successful modeling, rats in Tuina 1 group received manual pressing on nodules or cord-like taut bands on the medial aspect of the left hindlimb. Pain sensitivity and tissue stiffness were evaluated via pressure pain threshold (PPT) and soft tissue tension (STT). Muscle histopathology and fibrosis were observed using hematoxylin and eosin (HE) and Masson staining. Inflammatory factors in muscle were measured by enzyme-linked immunosorbent assay (ELISA), while immunofluorescence (IF) and Western blot (WB) were used to detect the expression levels of α-smooth muscle actin (α-SMA), collagen Ⅲ, and TGF-β1. In phase 2, 45 SPF female SD rats were randomized into five groups: control 2, model 2, Tuina 2, TGF-β1 inhibitor (TI), and Tuina + TGF-β1 agonist (Tuina + TA) groups. All groups except control 2 underwent standardized MTrPs modeling. Rats in Tuina 2 group received consistent pressing manipulation. TI group received intraperitoneal injections of oxymatrine, while Tuina + TA group received intraperitoneal injections of SRI-011381 hydrochloride followed by the same pressing protocol as Tuina 2 group. WB was used to detect the expression of collagen I, collagen III, TGF-β1, and phosphorylated-Smad3 (p-Smad3)/Smad3. Results In phase 1, Tuina significantly improved PPT and STT in MTrPs of rats (P < 0.01), reversed pathological damages including disorganized muscle fiber arrangement, abnormal myocyte morphology, and exacerbated fibrosis. In addition, in MTrPs of rats in model 1 group, expression levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and fibrosis markers (α-SMA, collagen I, and collagen III) were upregulated, and all exhibited a significant downward trend after Tuina intervention (P < 0.05 or P < 0.01). This indicates that the therapeutic effects of Tuina are directly associated with reduced local inflammation and fibrosis in MTrPs. In phase 2, compared with model 2 group, rats in TI and Tuina 2 groups had decreased expression levels of TGF-β1 and p-Smad3/Smad3 in MTrPs, alongside reduced levels of inflammatory factors (IL-1β, IL-6, NF-κB, and TNF-α) and fibrosis markers (α-SMA, collagen I, and collagen III) (P < 0.05 or P < 0.01). When co-administered with TGF-β1 agonist, the therapeutic effects of Tuina were significantly attenuated, with rebounded TGF-β1 expression and p-Smad3/Smad3 in local MTrPs, and fibrosis and inflammatory responses were re-exacerbated (P < 0.05 or P < 0.01). Conclusion Tuina can effectively reduce inflammatory responses and fibrosis in MTrPs tissue, and its mechanism is closely related to the inhibition of the TGF-β1/Smad3 signaling pathway, which plays a critical role in Tuina-mediated regulation of MTrPs fibrosis.

IntroductionQi-deficiency constitution is a common constitution among college students and has already affected their normal life and study. Baduanjin promotes the circulation of Qi and Blood, and replenishes vital energy, which is of great significance for improving the improving Qi deficiency constitution of college students. This study aims to explore the clinical effects of a 10-week practice of Baduanjin exercise on the sleep quality and emotional state of college students with Qi-deficiency constitution.Methods37 college students with Qi-deficiency constitution and sleep quality problems were randomly divided into 18 cases in the control group and 19 cases in the training group. We compared the Qi-deficiency constitution conversion score, Pittsburgh Sleep Quality Index (PSQI), Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) of the two groups before and after the intervention, and analyzed the correlation between the difference of the Qi-deficiency constitution conversion score and the difference of the total score of the PSQI as well as the clinical effectiveness of the two groups before and after the intervention.ResultsBefore the intervention, the two groups were comparable in terms of Qi-deficiency constitution conversion score, PSQI, SAS and SDS (P > 0.05). After the intervention, there was no significant difference in Qi-deficiency constitution conversion score, PSQI, SAS and SDS in the control group (P > 0.05); the training group's Qi-deficiency constitution conversion score, PSQI, SAS and SDS were lower than that of the group before the intervention (P < 0.05) and lower than that of the control group during the same period (P < 0.05). There was a significant positive correlation between the difference between the Qi-deficiency constitution conversion score and the difference between the total PSQI score before and after the intervention in the training group (P = 0.013). After the intervention, the total effective rate of the training group was higher than the control group (P < 0.001).ConclusionBaduanjin can effectively improve the sleep quality, Qi-deficiency constitution and negative emotions of depression and anxiety in college students with Qi-deficiency constitution, and it is positively correlated with the improvement of Qi-deficiency constitution in terms of the degree of sleep improvement.Clinical Trial Registration: identifier ITMCTR2025000103.

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.

Chronic pain is a multidimensional experience influenced by biological, psychological, and social factors. It frequently culminates in a reciprocal “pain-emotion” vicious cycle involving comorbid anxiety and depression. This study investigated the therapeutic potential of affective tactile stimulation in a rat model of chronic inflammatory pain with anxiety, focusing on the afferent pathways and the regulatory role of the hippocampal CA1 region. Through behavioral assays and optogenetic interventions, we demonstrated that affective tactile stimulation partially ameliorates pain hypersensitivity, exerts a mild modulatory effect on peripheral inflammatory responses, and effectively alleviates anxiety-like behaviors. Mechanistically, affective tactile stimulation appears to integrate sensory information within the tactile cortex to modulate neural activity in the hippocampal CA1, a key regulatory hub. Enhanced CA1 neuronal activity was found to correlate closely with symptom improvement. Furthermore, our results suggest that oscillatory enhancement in the theta and delta bands, alongside functional connectivity remodeling, might play a critical role in these effects. These findings provide a neurobiological foundation for the clinical application of affective tactile stimulation in managing chronic inflammatory pain and associated affective disorders.

Backgroud Prenatal exposure to valproic acid (VPA) is an important environmental risk factor for autism spectrum disorder (ASD), yet the mechanisms underlying VPA-induced ASD-like phenotypes and male-biased susceptibility remain unclear. Emerging evidence suggests that VPA exposure may induce neuronal ferroptosis and contribute to neurodevelopmental impairment. However, whether VPA-induced neuronal ferroptosis in the brain exhibits developmental-stage- and sex differences remains to be elucidated. Methods Adolescent male and female C57BL/6 mice exposed to VPA at embryonic day 12.5 (E12.5) or postnatal day 14 (PND14) were used to examine developmental-stage- and sex differences effects of VPA exposure. Sociability and anxiety-like behaviors were assessed using the three-chamber social interaction test (3-CT) and open field test (OFT), respectively. Histological alterations in ASD-related brain regions, including the medial prefrontal cortex (mPFC), hippocampus, and striatum, were examined by hematoxylin-eosin (HE) and Nissl staining, while ferroptosis-related changes were evaluated using biochemical assays, immunofluorescence, transmission electron microscopy, and Western blotting. To elucidate the molecular changes associated with ferroptosis and the behavioral and morphological alterations in brain tissue of mice exposed to VPA at various developmental stages, comparisons were conducted between E12.5 and PND14 VPA exposure models. This study aimed to investigate potential differences in exposure windows linked to ASD-like behavioral and neuropathological changes in relation to ferroptosis-related modifications. Results Both male and female adolescent offspring exposed to VPA exhibited social deficits and anxiety-like behaviors, with a more pronounced phenotype in males, particularly in social preference and sociability. Histological analysis revealed neuronal abnormalities in the mPFC, hippocampus, and striatum of VPA-exposed offspring, with the most prominent alterations observed in the male mPFC. Consistently, ferroptosis-related molecular changes were most evident in the mPFC and were accompanied by marked mitochondrial abnormalities and vacuolization. These alterations exhibited a distinct pattern of sex differences, revealing that males are more vulnerable than females. Additionally, in male offspring, both prenatal and early postnatal exposure to VPA resulted in similar behavioral abnormalities and ferroptosis-related changes in the mPFC. Conclusion This study indicates that exposure to VPA may contribute to the development of ASD-like lesions by inducing ferroptosis-related neuronal damage, with male offspring exhibiting greater susceptibility. The mPFC appears to be a critical brain region vulnerable to these effects. Both prenatal and postnatal VPA exposure can elicit comparable levels of ferroptosis-related molecular alterations, suggesting that ferroptosis may serve as a shared pathological mechanism underlying ASD-like neurodevelopmental abnormalities resulting from VPA exposure during various developmental windows.

Introduction:Neck pain is the fourth leading cause of disability worldwide. In China, primary care institutions face considerable challenges in the management of neck pain, primarily due to insufficient allocation of medical resources, resulting in an overreliance on pharmacological interventions in clinical practice. As an evidence-based and standardized non-pharmacological therapy, Tuina (Jingjin) offers distinct advantages in primary care settings, including high safety profiles and strong patient acceptance. However, its application and dissemination in frontline primary healthcare practice remain insufficient. The primary aim of this study will be to identify the barriers and facilitators for implementing Tuina (Jingjin) in primary care settings in China from the perspectives of multiple stakeholders. Methods:This qualitative study will utilize the five core domains of the Consolidated Framework for Implementation Research (CFIR 2.0)-Intervention Characteristics, Outer Setting, Inner Setting, Individual Characteristics, and Process-to inform the development of a semi-structured interview guide and data analysis. Recruitment will target patients with neck pain, traditional Chinese medicine general practitioners, and institutional managers from geographically diverse primary care institutions across China, with the sample size contingent upon achieving information saturation. Discussion:This study will contribute to the understanding of the multi-level factors that influence the implementation of Jingjin Tuina and provide strategies to enhance the adoption of this evidence-based intervention in primary care settings with limited resources.

BACKGROUND:Low back pain (LBP) is one of the most common symptoms prompting patients to seek treatment. Manual therapy is widely used to treat LBP. Nevertheless, there is a scarcity of bibliometric analyses examining the worldwide utilization of manual therapy for the treatment of LBP. METHODS:This research used the Online Bibliometric overview Platform website (https://bibliometric.com), CiteSpace (6.2.R4), and VOSviewer (1.6.19) to provide a comprehensive analysis of the current status and prospective developments in the field. The Web of Science Core Collection (WOSCC) database was searched for publications from August 1, 2013, to August 1, 2023 on manual therapy of low back pain. RESULTS:Among the identified articles, 488 fit the criteria. The number of papers on manual therapy for LBP has progressively risen over in the past 10 years, whereas the average number of citations of these papers has decreased. The leading countries producing publications on this discipline were the USA, Canada, and China. There were 345 authors of the studies, with Christine M. Goertz having the most publications. The University of Southern Denmark was the institution that contributed the most to the field. The Journal of Manipulative and Physiological Therapeutics published many of the research papers in this field. Keyword analysis showed that the relationship between low back pain, spinal manipulation, and management has been present throughout the development of this research area. CONCLUSIONS:Spinal manipulation, management, randomized controlled trials, Physical therapy, care and disability are the current research hotspots in the treatment of LBP with manual therapy. In addition, research on complementary medicine and clinical practice guidelines may become an important trend in the future.

OBJECTIVE:To evaluate the clinical efficacy of combining interference electrotherapy with rotary traction manipulation in treating cervical spondylotic radiculopathy (CSR), and to assess its impact on cervical function and prognosis. METHODS:A retrospective analysis was conducted on the clinical data from 214 CSR patients who were treated at Yueyang Central Hospital, Hunan University of Chinese Medicine, from April 2021 to October 2023. The observation group (n=110) received combined therapy using interference electrotherapy and rotary traction manipulation, while the control group (n=104) received rotary traction manipulation alone. Before treatment, and at 2 and 4 weeks post-treatment, cervical function was assessed using the Neck Disability Index (NDI), and pain intensity was measured using components of the Simplified McGill Pain Questionnaire (SF-MPQ), including Visual Analog Scale (VAS), Present Pain Intensity (PPI), and Pain Rating Index (PRI). Clinical efficacy was evaluated using the modified Macnab criteria, and treatment safety was assessed. Both groups were followed up for one year to record recurrence rates. Logistic regression was used to identify risk factors for recurrence. RESULTS:Baseline characteristics were similar between groups (P>0.05). After 2 and 4 weeks, the observation group showed significantly greater improvements in NDI, VAS, PRI, and PPI scores compared to the control group (P<0.001). The total effective rate was higher in the observation group (92.7%) than in the control group (80.8%) (P=0.017). However, the recurrence rate was significantly higher in the observation group (7.3%) compared to the control group (20.2%) (P=0.006). Logistic regression identified treatment regimen, patient age, and pillow height as independent risk factors for recurrence (P<0.05). A recurrence risk scoring model based on these factors achieved an AUC of 0.897 (95% CI: 0.844-0.951). CONCLUSION:Combining interference electrotherapy with rotary traction manipulation significantly improves cervical function and alleviates pain in CSR patients, yielding higher overall efficacy. However, this combination is associated with an increased risk of recurrence, influenced by treatment method, patient age, and pillow height.

BACKGROUND:Neck pain is a common global health problem and a leading cause of disability, imposing significant personal and societal burdens. Musculoskeletal manipulations are recommended as the first-line treatment for neck pain in clinical practice guidelines, valued for their non-invasive and cost-effectiveness. OBJECTIVE:To determine the most effective musculoskeletal manipulation for neck pain by integrating both direct and indirect evidence through a network meta-analysis, enabling comparisons among interventions even in the absence of direct head-to-head evidence. DESIGN:Systematic review and network meta-analysis. DATA SOURCES:Web of Science, the Cochrane Library, Embase, PubMed, Clinical Trials Registry, China National Knowledge Infrastructure, VIP Database and Wanfang Data were searched from January 2013 to May 2025. ELIGIBILITY CRITERIA:Randomised controlled trials (RCTs) involving adults (aged ≥18 years) with neck pain receiving musculoskeletal manipulations. DATA EXTRACTION AND SYNTHESIS:Paired reviewers independently extracted data. The primary outcome was pain intensity, assessed using the visual analogue scale or numeric rating scale (with total scores of 10 or 100 points). Secondary outcomes included neck disability measured by the neck disability index (with total scores of 50 or 100 points), cervical range of motion (flexion and extension) measured in degrees using a universal goniometer and adverse events. All included studies were assessed for risk of bias using the RoB 2.0 tool and categorised as 'low', 'some concerns' or 'high'. A frequentist random-effects network meta-analysis was conducted to calculate weighted mean differences with its 95% confidence intervals were calculated. Comparison-adjusted funnel plots were used to assess publication bias when 10 or more studies were included, and the Grading of Recommendations, Assessment, Development and Evaluations approach was applied for the quality of evidence. RESULTS:A total of 101 RCTs involving 7633 participants were included. Overall, 62 (61.3%) had high risk of bias, 18 (17.8%) had some concerns and 21 (20.7%) had low risk of bias. Moderate to very low-certainty evidence showed significant reduction in neck pain intensity compared with no treatment: multimodal treatment (pooled weighted mean difference (WMD): -36.65, 95% CI -61.02 to -12.28), active control (pooled WMD: -36.62, 95% CI -62.67 to -10.57), manual therapy (pooled WMD: -35.85, 95% CI -59.86 to -11.83), soft tissue technique (pooled WMD: -28.72, 95% CI -51.65 to -4.79) and mobilisation (pooled WMD: -20.23, 95% CI -39.87 to -0.06), with multimodal treatment being the most effective intervention (surface under the cumulative ranking curve (SUCRA)=100%). No publication bias was detected for neck pain intensity. Moreover, multimodal treatment was the most effective for reducing neck disability (SUCRA=96.3%), whereas manipulation was the most effective for improving cervical range of flexion (SUCRA=81.3%) and extension (SUCRA=78.2%). CONCLUSION:Multimodal treatment (the combined use of two or more musculoskeletal manipulations) is the most effective intervention for reducing both neck pain intensity and neck disability. Manipulation is the most effective for improving cervical range of motion.

Jing Chen,1–4 Wu Li,1,4 Jiangshan Li1,4 1School of Acupuncture, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China; 2College of Medical Imaging Laboratory and Rehabilitation, Xiangnan University, Chenzhou, Hunan, People’s Republic of China; 3Department of Rehabilitation Medicine, The Affiliated Hospital of Xiangnan University, Chenzhou, Hunan, People’s Republic of China; 4Department of Acupuncture, Tuina and Rehabilitation, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Jiangshan Li; Wu Li, School of Acupuncture, Tuina and Rehabilitation, Hunan University of Chinese Medicine, No. 300, Xueshi Road, Yuelu District, Changsha, Hunan Province, 410208, People’s Republic of China, Tel +86 13707315642; +86 13574851647, Fax +8673188458187, Email 292463008@qq.com; 272434694@qq.com

Synaptic abnormalities are hallmark pathological features of autism spectrum disorders (ASD), contributing to the behavioral impairments frequently observed in these neurodevelopmental conditions. Microglia, as the brain’s primary immune cells, are essential for synaptic refinement during adolescent development. Disrupted microglia-dependent synapse remodeling has been implicated in pathophysiology of ASDs, however, the underlying mechanisms remain incompletely elucidated. In this context, repetitive unidirectional spinal tactile stimulation (RSTS) has emerged as a promising non-invasive therapeutic strategy. This study aims to explore whether and how RSTS enhances microglia-dependent synapse remodeling in the medial prefrontal cortex (mPFC) during adolescent development in ASD mice, with a specific focus on the role of Brain and Muscle ARNT-Like 1 (Arntl1), a core circadian protein crucial for regulating this process. ASD mice underwent RSTS treatment during adolescent brain for 21 days, administered twice daily for 10 min per session. Behavioral changes were evaluated using the three-chamber social interaction and open field tests. Synapse number and morphology were assessed through Golgi staining. Microglia-dependent synapse remodeling ability was analyzed using immunofluorescence and Western blot. Furthermore, the molecular mechanism was investigated using single-nucleus RNA sequencing (snRNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq). Finally, the role of Bmal1 was validated, confirming its involvement in the enhancement of RSTS during adolescent brain in ASD. RSTS was found to alleviate autistic-like behaviors in adolescent ASD mice. Results from snRNA-seq and ChIP-seq indicated that the therapeutic effects of RSTS may be mediated through microglial Bmal1 and its role in the transcriptional regulation of microglia-dependent synapse remodeling. Furthermore, in vivo experiments confirmed that RSTS enhances microglia-dependent synapse remodeling in mPFC of adolescent ASD mice via Bmal1. These findings suggested that Bmal1 serves as a critical target of RSTS in facilitating microglia-dependent synapse remodeling during the adolescent brain developmental period in ASD mice. Our findings suggest that the therapeutic effects of RSTS are potentially mediated through the modulation of microglial Bmal1-dependent synapse remodeling and the regulation of synaptic proteins and the complement system. These results provide novel empirical evidence for RSTS in restoring synaptic balance and offer valuable insights into its potential as an intervention for ASD. A diagram of the proposed mechanism by which RSTS promotes microglia-dependent synapse remodeling during adolescent brain development in ASD through Bmal1. ① ASD mice exhibit an excess of immature synapses; ②RSTS is applied as a therapeutic intervention; ③RSTS increases the expression of Bmal1 enhances its transcriptional regulatory activity in ASD mice brain; ④RSTS upregulates the expression of CD68, CR3, C1q, and C3b in ASD mice microglia; ⑤Bmal1 promotes expression of Wnt/β-catenin downstream targets (e.g., CyclinD1, C-Myc, Prox1) and interacts with TCF4 to modulate transcription;⑥RSTS lowers the expression of synaptic markers (e.g., PSD95, Syn1), reduces total synapse number, and decreases the proportion of immature synapses, indicating synaptic normalization in VPA-exposed mice.

Chronic pain frequently coexists with adverse emotions, including anxiety and depression, significantly affecting patients' physical and psychological health as well as their quality of life. Changes in hippocampal synaptic architecture, neuronal injury, and diminished neurogenesis significantly contribute to pain-related emotions. Microglia in the hippocampus are implicated in these pathologies. Stimulation or injury leads to microglial activation, which causes pain; prolonged pain causes microglia to continuously release pro-inflammatory factors that induce astrocyte activation, which mediates the apoptosis of hippocampal neurons and abnormal neurogenesis. Concurrently, microglia exhibit aberrant phagocytosis and augmented pruning of hippocampal dendritic spines, which disrupts synaptic plasticity and influences hippocampal long-term potentiation, hence contributing to the emergence of negative emotions. Inflammatory responses in the brain are a prevalent pathological foundation for mood disorders and pain, and the activation or inhibition of microglia M1 polarization can influence pain-related emotions. This review elucidates the significance of hippocampal microglia activation, and their interactions with neurons in the hippocampus and astrocytes, in pain-related emotions.

Purpose:To evaluate whether Jingjin therapy, a distal manual intervention, could accelerate extension dysfunction for non-specific chronic neck pain (NCNP). Patients and Methods:In this single-centre, two-arm randomised controlled trial, we enrolled Chinese patients aged 20-60 years with active neck extension disorder, regardless of prior exposure to manual therapy. We randomly assigned 160 patients to one of the following two arms: Jingjin therapy or general manual therapy. Both groups underwent six treatment sessions: the first three sessions were administered daily, and the last three sessions were administered every other day. The primary outcome was the between-group difference in the angle of active neck extension after the sixth treatment and 1 week after treatment. A repeated-measures linear mixed-effects model was used to assess between-group differences in outcome indices, with group allocation and treatment time points treated as fixed effects and participants as random effects. Results:The change in the angle of active neck extension from baseline to the sixth treatment session was significant for Jingjin therapy (mean: 29.75° to 51.97°) and general manual therapy (mean: 28.18° to 52.49°). Further, the between-group difference was minimal (mean -0.26°, 95% confidence interval, -2.62°, 2.09°) and not statistically significant (P = 0.828). Conclusion:Jingjin therapy for 9 days significantly improved neck extension function in patients with NCNP, with no significant difference compared to general manual therapy. Clinical Trial Registry Id:ChiCTR2300068892.

Background Synaptic abnormalities are hallmark pathological features of autism spectrum disorders (ASD), contributing to the behavioral impairments frequently observed in these neurodevelopmental conditions. Microglia, as the brain’s primary immune cells, are essential for synaptic refinement during adolescent development. Disrupted microglial-mediated synaptic pruning has been implicated in pathophysiology of ASDs, however, the underlying mechanisms remain incompletely elucidated. In this context, repetitive unidirectional spinal tactile stimulation (RSTS) has emerged as a promising non-invasive therapeutic strategy. By delivering gentle, unidirectional tactile stimulation to the skin surface over spinal region, RSTS has been shown to modulate microglial function and effectively restore synaptic balance. Objective This study aims to explore how RSTS enhances microglial synaptic pruning in the medial prefrontal cortex (mPFC) during adolescent development in ASD mice, with a specific focus on the role of Brain and Muscle ARNT-Like 1 ( Arntl1 ), a core circadian protein crucial for regulating this process. Methods ASD mice underwent RSTS treatment during adolescent brain development for 21 days, administered twice daily for 10 minutes per session. Behavioral changes were evaluated using the three-chamber social interaction and open field tests. Synapse number and morphology were assessed through Golgi staining. To determine the therapeutic effects of RSTS during adolescent brain development, microglial synaptic pruning and synaptic protein expression were analyzed using immunofluorescence staining and Western blot. Furthermore, the molecular mechanism underlying the synapse pruning implications of RSTS in ASD during adolescent were comprehensively investigated using single-nucleus RNA sequencing (snRNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq). Finally, the role of Bmal1 was validated in Bmal1 knockout mice, confirming its involvement in the enhancement of microglial synaptic pruning by RSTS during adolescent brain development in ASD. Results RSTS was found to alleviate autistic-like behaviors in adolescent ASD mice during brain development. Results from snRNA-seq and ChIP-seq analyses indicated that the therapeutic effects of RSTS may be mediated through microglial Bmal1 and its role in the transcriptional regulation of microglial synaptic pruning. Furthermore, in vivo experiments confirmed that RSTS enhances microglial synaptic pruning in mPFC of adolescent ASD mice via Bmal1. These findings suggested that Bmal1 serves as a critical target of RSTS in facilitating microglial pruning during the adolescent brain developmental period in ASD mice. Conclusion This study represents the first comprehensive investigation into the underlying mechanisms of RSTS in treating ASD, utilizing single-cell sequencing, gene-knockout mice, and complementary molecular analyses. Our findings suggest that the therapeutic effects of RSTS are potentially mediated through the modulation of Bmal1 -dependent microglial synaptic pruning and the regulation of key synaptic proteins and the complement system. These results provide novel empirical evidence for the role of RSTS in restoring synaptic balance and offer valuable insights into its potential as an intervention for ASD, further elucidating the regulatory pathways through which Bmal1 contributes to neurodevelopmental disorders.