Transcriptome profiling of microRNAs reveals potential mechanisms of manual therapy alleviating neuropathic pain through microRNA-547-3p-mediated Map4k4/NF-κb signaling pathway.

BACKGROUND: Local neuroinflammation secondary to spinal nerve compression in lumbar disk herniation (LDH) is a key driver contributing to neuropathic pain. Manual therapy (MT), a widely used nonsurgical therapy, can relieve LDH-mediated pain by reducing inflammation. MT has attracted extensive attention; however, its mechanism remains poorly understood. MicroRNAs (miRNAs) are important regulators of pain signaling transduction, but are rarely reported in the chronic compression of dorsal root ganglia (CCD) model, and further investigation is needed to decipher whether they mediate anti-inflammatory and analgesic effects of MT. METHODS: We used a combination of in vivo behavioral and molecular techniques to study MT intervention mechanisms. Neuropathic pain was induced in a CCD rat model and MT intervention was performed according to standard procedures. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory cytokine levels in dorsal root ganglia (DRG). Small RNA sequencing, immunofluorescence, Western blot, and qRT-PCR were performed to screen miRNAs and their target genes and determine core factors in the pathway possibly regulated by miRNA-mediated target gene in DRG of MT-treated CCD rats. RESULTS: Compared with naive rats, small RNA sequencing detected 22 differentially expressed miRNAs in DRG of CCD rats, and compared with CCD rats, MT-treated rats presented 19 differentially expressed miRNAs, which were functionally associated with nerve injury and inflammation. Among these, miR-547-3p was screened as a key miRNA mediating neuroinflammation and participating in neuropathic pain. We confirmed in vitro that its function is achieved by directly regulating its target gene Map4k4. Intrathecal injection of miR-547-3p agomir or MT intervention significantly reduced Map4k4 expression and the expression and phosphorylation of IκBα and p65 in the NF-κB pathway, thus reducing the inflammatory cytokine levels and exerting an analgesic effect, whereas intrathecal injection of miR-547-3p antagomir led to opposite effects. CONCLUSIONS: In rats, CCD-induced neuropathic pain leads to variation in miRNA expression in DRG, and MT can intervene the transcription and translation of inflammation-related genes through miRNAs to improve neuroinflammation and alleviate neuropathic pain. MiR-547-3p may be a key target of MT for anti-inflammatory and analgesia effects, which is achieved by mediating the Map4k4/NF-κB pathway to regulate downstream inflammatory cytokines.

[Complex mechanisms of chronic pain in knee osteoarthritis identified by neuroimaging technology].

Chronic pain of knee osteoarthritis (KOA) greatly affects the quality of life and functional activities of patients. It is important to clarify the underlying mechanisms of KOA pain and the analgesic effect of different therapies. Neuroimaging technology has been widely used in the basic and clinical research of pain. In the recent years, neuroimaging technology has played an important role in the basic and clinical research of KOA pain. Increasing evidence demonstrates that chronic pain in KOA includes both nociceptive and neuropathic pain. The neuropathic mechanism involved in KOA pain is complex, which may be caused by peripheral or central sensitization. In this paper, we review the regional changes of brain pathophysiology caused by KOA pain based on magnetic resonance imaging (MRI), electroencephalogram (EEG), magnetoencephalogram (MEG), near-infrared spectroscopy (NIRS) and other neuroimaging techniques. We also discuss the central analgesic mechanism of different KOA therapies, with a focus on the latest achievements in the evaluation and prediction of pain. We hope to provide new thoughts for the treatment of KOA pain, especially in the early and middle stages of KOA.

Joint Angles and Joint Moments of the Lower Limbs in Four Typical Tai Chi Movements: Consideration for Management of Knee Osteoarthritis.

This study examined the biomechanics of the lower limbs during four typical Tai Chi (TC) movements: wave hand in cloud, leaning fly side, repulse monkey, and brush knee and twist step, in order to provide biomechanical evidence-based recommendations for patients with knee osteoarthritis (OA) practicing TC. Joint angles and joint moments of the hip, knee, and ankle in frontal and sagittal plane as well as ground reaction forces were examined while performing TC and regular walking in an experienced 38 years old TC master. The results showed that relative to walking, the four TC movements are characterized by a wide motion range of lower limbs, slow increase in joint loading, and strong muscle activity during performance. Therefore, these TC movements could be suitable for patients with knee OA to practice for improving the muscle strength of their lower limbs and functional ability.

The effects of shoes and insoles for low back pain: a systematic review and meta-analysis of randomized controlled trials.

The aim of this review was to examine the effects of shoes and insoles on low back pain (LBP). Seven electronic databases were searched from their inception to May 2020. The methodological quality of the 14 included studies was assessed by PEDro scale. Quality of evidence was assessed using GRADE. Moderate evidence on the disability questionnaire score (SMD, 0.52; 95% CI, 0.28 to 0.77; P < 0.001) and pain score (SMD, 0.61; 95% CI, 0.36 to 0.85; P < 0.001) of the custom-made orthotics for chronic LBP compared with no orthotics/insoles intervention was found. Meta-analysis results also showed moderate evidence on the disability questionnaire score (SMD, 0.44; 95% CI, 0.05 to 0.82; P =0.03) in patients who wore unstable shoes compared with regular shoes. Pain and life quality scores showed low-quality evidence of unstable shoes for chronic LBP. Custom-made orthotics and unstable shoes can be recommended to patients as a management option of chronic LBP.

[Effect of Chinese massage (Tui Na) on isokinetic muscle strength in patients with knee osteoarthritis].

OBJECTIVE: Chinese massage (Tui Na) is one of the most popular Traditional Chinese Medicine remedies for knee osteoarthritis (OA). Several studies have subjectively evaluated the effect of Chinese massage on knee OA through self-assessment questionnaires; however, very few studies have objectively assessed the effect by measuring knee muscle strength. The purpose of this study was to assess the efficacy of Chinese massage in improving knee extensor and flexor muscle strength in patients with knee OA. METHODS: Thirty patients with knee OA received Chinese massage therapy three times per week for 2 weeks. Patients completed pre- and post-treatment Visual Analogue Scale (VAS) pain questionnaires, and pre- and post-treatment knee muscle strength was evaluated using the Biodex Multi-Joint System 3. Isokinetic muscle strength measurements were performed at 60 degrees/s and 180 degrees/s. The peak torque (PT), peak torque/body weight(PT/BW), total work (TW), average power (AP), hamstring/quadriceps (H/Q), and range of motion (ROM) values were recorded separately for flexors and extensors. RESULTS: Chinese massage therapy significantly improved knee pain as assessed by the VAS in patients with knee OA (P < 0.05). Post-treatment values were significantly greater than pre-treatment values in the extensor muscles for PT (right P = 0.013, left P = 0.001), PT/BW (right P = 0.008, left P = 0.001) and TW (right P = 0.036, left P = 0.004) at 60 degrees/s. The AP increased significantly after treatment in the flexor muscles in the right knee (P = 0.009) and the extensor muscles in the left knee (P = 0.001). There were no significant differences in pre- and post-treatment ROM and H/Q at 60 degrees/s and 180 degrees/s. CONCLUSION: Chinese massage therapy decreased pain and may improve extensor muscle strength in patients with knee OA, but does not appear to improve ROM.

The effects of manual therapy in pain and safety of patients with knee osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Manual therapy (MT) is frequently used in combination with management of osteoarthritis of the knee, but there is no consensus on the exact efficacy of this treatment strategy. The purpose of this systematic review and meta-analysis was to evaluate the pain relief and safety of MT for treatment of knee osteoarthritis (KOA). METHODS: Randomized controlled trials evaluating MT in patients with KOA in major English and Chinese journals were searched in the following databases: Wanfang, China Science and Technology Journal Database (VIP database), China National Knowledge Infrastructure (CNKI), PubMed, Embase, Web of Science, and the Cochrane Library databases through June 2023. The methodological quality and quality of evidence of the included studies were assessed using Cochrane's risk-of-bias 2 (ROB 2) tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. Data analysis was performed using Stata version 15.0 software. After use of Galbraith plots to exclude studies that could lead to heterogeneity, random effects models were used to analyze the remaining data and test the consistency of the findings. We used meta-regression to assess the effect of treatment period, patient age, and sex ratio on outcomes. Funnel plots and Egger's test were used to evaluate publication bias. Sensitivity analyses were used to determine the reliability of the results. RESULTS: A total of 25 studies, with 2376 participants, were included in this review. The overall methodological quality of the included studies was limited. Our findings suggest that MT has a positive impact on pain relief outcomes in KOA patients. The meta-analysis showed that MT was superior to usual care (SMD = 2.04, 95% CI 0.94, 3.14, I 2 = 96.3%; low evidence quality) and exercise (SMD = 1.56, 95% CI 0.41, 2.71, I 2 = 96.3%; low evidence quality) for reducing pain. In terms of improvement in visual analogue scale (VAS) scores, MT treatment beyond 4 weeks (SMD = 1.56, 95% CI 0.41, 2.71, I 2 = 96.3%) may be superior to treatments less than or equal to 4 weeks (SMD = 1.24, 95% CI 0.56, 1.95, I 2 = 94.7%). No serious adverse events associated with MT were reported. CONCLUSIONS: MT may be effective at reducing pain in patients with KOA and may be more effective after a 4-week treatment period. Compared with usual care and exercise therapy, MT may be superior at reducing KOA pain in the short term (9 weeks), but its long-term efficacy requires careful consideration of evidence-based outcomes. MT appears to be safe for KOA patients, though clinicians should inform patients of the potential risk of MT-related adverse events.

Hidden delta degradation due to fluvial sediment decline and intensified marine storms.

Deltas are threatened by erosion due to climate change and reduced sediment supply, but their response to these changes remains poorly quantified. We investigate the abandoned Yellow River delta that has transitioned from rapid growth to ongoing deterioration due to a river avulsion removing the sediment supply. Integrating bathymetric data, process observations, and sediment transport modeling, we find that while the subaerial delta was stabilized by engineering measures, the subaqueous delta continued to erode due to intensified storms, losing 39% of its mass deposited before the avulsion. Long-term observations show that winter storms initiate scouring of the subaqueous delta, contributing up to 70% of seabed erosion. We then analyze 108 global deltas to assess subaqueous delta erosion risks and identify 17 deltas facing similar situations of sediment decline and storm intensification during the past 40 years. Our findings suggest that subaqueous delta erosion must be integrated into delta sustainability evaluations.

Efficacy and safety of traditional Chinese manual therapy (Tuina) in patients with non-specific chronic low back pain: a study protocol for a randomised controlled trial.

INTRODUCTION: Non-pharmacological interventions play a crucial role in the management of non-specific chronic low back pain (NSCLBP). One prime example is Tuina, a traditional Chinese manual therapy that incorporates pressing, kneading and rubbing techniques to alleviate physical discomfort and enhance overall well-being. It serves as a widely used technique in China and other East Asian countries. However, the effectiveness and safety of Tuina for managing NSCLBP have not been substantiated through rigorous clinical research. We sought to carry out a randomised controlled trial with an open-label design, blinded assessors and parallel arms to assess the effectiveness and safety of Tuina as a treatment for NSCLBP. The trial aims to provide high-quality evidence regarding the efficacy and safety of Tuina in improving outcomes for patients with NSCLBP. METHODS AND ANALYSIS: A total of 150 patients aged 18-60 years with NSCLBP will be recruited. Participants will be randomly assigned to one of the two groups. Both groups will receive standard health education. In addition, the treatment group will receive Tuina therapy, while the control group will participate in core stability exercises. Each group will undergo a total of 18 interventions over 6 weeks, with the interventions administered three times per week. The primary outcome measure is the patient's pain intensity, assessed using the Numerical Rating Scale, at week 6 following randomisation. Secondary outcomes encompass disability (measured by the Roland-Morris Disability Questionnaire), quality of life (assessed using the EuroQoL-5 dimensions questionnaire), adverse emotions (evaluated with the Pain Catastrophizing Scale, Tampa Scale of Kinesiophobia and Depression Anxiety Stress Scale), biomechanical outcomes, socioeconomic indicators (medication use, healthcare utilisation and absenteeism), patient satisfaction, treatment adherence and other relevant factors.The statistical analysis will follow the intention-to-treat principle. Two-way repeated measures analysis of variance will be used to compare the clinical data across different time points within both groups. ETHICS AND DISSEMINATION: The study protocol has received approval from the Ethics Committee of Shuguang Hospital, Shanghai University of Traditional Chinese Medicine (2023-1366-133-01). All study participants will be required to give 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. TRIAL REGISTRATION NUMBER: ChiCTR2300076257.

Effects of a biomechanical-based Tai Chi program on gait and posture in people with Parkinson's disease: study protocol for a randomized controlled trial.

BACKGROUND: Parkinson's disease (PD) is associated with changes in gait and posture, which increases the rate of falls and injuries in this population. Tai Chi (TC) training enhances the movement capacity of patients with PD. However, the understanding of the effect of TC training on gait and postural stability in PD is lacking. This study aims to examine the effect of biomechanical-based TC training on dynamic postural stability and its relationship with walking performance. METHODS/DESIGN: A single-blind, randomized control trial of 40 individuals with early-stage PD was conducted (Hoehn and Yahr stages 1 to 3). Patients with PD will be randomly assigned to either the TC or control group. The TC group will participate in a biomechanical-based TC training program that is formed based on the movement analysis of TC and will be practiced thrice a week for 12 weeks. The control group will be required to engage in at least 60 min of regular physical activity (PA) on their own for three times per week for 12 weeks. The primary and secondary outcomes will be assessed at baseline and at 6 and 12 weeks after commencing the study protocol. The primary outcome measures will include dynamic postural stability indicated by the center of mass and center of pressure separation distance and clearance distance of the heel and toe measured during fixed-obstacle crossing. The secondary measures are gait speed, cadence, step length during level surface walking (simple task), and fixed-obstacle crossing (challenging task). The Unified Parkinson's Disease Rating Scale, single leg-stance test with eyes open and closed, and three cognitive scores (Stroop Test, Trail Making Test Part B, and the Wisconsin Card Sorting Test) were also employed. DISCUSSION: This protocol could lead to the development of a biomechanics TC training program for the improvement of gait and postural stability among individuals with PD. The program could enhance the understanding of the effect of TC training on gait and postural stability and could help improve or preserve the postural stability, self-confidence, and active participation in social activities of the participants, thus enhancing their overall quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT04644367. Registered on 25 November 2020.

Efficacy of traditional Chinese exercise for the treatment of pain and disability on knee osteoarthritis patients: a systematic review and meta-analysis of randomized controlled trials.

Objective: To evaluate the efficacy of Traditional Chinese Exercises (TCEs) in treating knee osteoarthritis (KOA). Methods: Four databases without language or publication status restrictions were searched until April 1, 2022. Based on the principle of Population, Intervention, Comparison, Outcomes and Study design, the researchers searched for randomized controlled trials of TCEs in treating KOA. The Western Ontario and McMaster Universities Osteoarthritis (WOMAC) pain was defined as the primary outcome, whereas stiffness and physical function were the secondary outcomes. Subsequently, two researchers conducted the process independently, and the data were analyzed using the RevManV.5.3 software. Results: Overall, 17 randomized trials involving 1174 participants met the inclusion criteria. The synthesized data of TCEs showed a significant improvement in WOMAC pain score [standardized mean difference (SMD) = -0.31; 95% confidence interval (CI): -0.52 to -0.10; p = 0.004], stiffness score (SMD = -0.63; 95% CI: -1.01 to -0.25; p = 0.001) and physical function score (SMD = -0.38; 95% CI: -0.61 to -0.15; p = 0.001) compared with the control group. Sensitivity analyses were performed to determine the combined results' stability, which was unstable after excluding articles with greater heterogeneity. A further subgroup analysis showed that it might be the reason for the heterogeneity of the different traditional exercise intervention methods. Additionally, it showed that the Taijiquan group improved pain (SMD = 0.74; 95% CI: -1.09 to 0.38; p < 0.0001; I2 = 50%), stiffness (SMD = -0.67; 95% CI -1.14 to 0.20; p = 0.005) and physical function score (SMD = -0.35; 95% CI: -0.54 to 0.16; p = 0.0003; I2 = 0%) better than the control group. The Baduanjin group improved stiffness (SMD = -1.30; 95% CI: -2.32 to 0.28; p = 0.01) and physical function (SMD = -0.52; 95% CI: -0.97 to 0.07; p = 0.02) better than the control group. However, the other interventions showed no difference compared with the control group. Conclusion: This systematic review provides partial evidence of the benefits of TCEs for knee pain and dysfunction. However, due to the heterogeneity of exercise, more high-quality clinical studies should be conducted to verify the efficacy. Systematic review registration: https://inplasy.com/inplasy-2022-4-0154/, identifier: International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) [INPLSY202240154].

Resting-state functional magnetic resonance imaging reveals brain remodeling after Tuina therapy in neuropathic pain model.

Tuina, a method of traditional Chinese manual manipulation, is an effective alternative therapy for neuropathic pain (NP), but its analgesic mechanism remains unclear. In this study, we used resting-state functional magnetic resonance imaging (R-fMRI) to explore the analgesic mechanism of Tuina in an NP rat model. After undergoing surgery to induce chronic compression of the dorsal root ganglion (CCD), one group of rats underwent Tuina at the ipsilateral BL40 acupoint once a day for 10 min during the 25 days following surgery while another group did not. Behavioral tests were performed at baseline, on the third day following surgery, and once a week for the next 4 weeks. R-fMRI was performed at baseline and 7 days and 28 days following surgery. Behavioral testing revealed that the Tuina group presented a significant response improvement to mechanical and thermal nociception stimuli compared to the untreated group 2 weeks following CCD surgery. Interestingly, rats submitted to Tuina presented higher measures of spontaneous neuronal activity in basal forebrain region, primary somatosensory cortex barrel field, dentate gyrus, secondary somatosensory cortex, striatum, descending corticofugal pathways, and globus pallidum of the left hemisphere 4 weeks after the CCD surgery compared to rats having undergone CCD only. In addition, on the 28th day, the ALFF signals of the left dentate gyrus, left secondary somatosensory cortex, left striatum, and bilateral primary cingulate cortex were significantly increased while those in the right dentate gyrus and bilateral periaqueductal gray were significantly decreased compared to those on the 7th day. Correlation analysis showed that the ALFF values of the left descending corticofugal pathways and globus pallidum had a positive correlation with mechanical withdrawal threshold and paw withdrawal thermal latency tests. Altogether, these results indicate that NPP induced by CCD surgery affects the plasticity of the cerebral cortex, and that Tuina alleviate pain behavior by promoting cortical remodeling.

[Effects of tuina manipulation on the three-dimensional space of cervical vertebral segments of cervical spondylosis patients].

OBJECTIVE: To study the mechanisms of tuina manipulation for treating the dislocation of bone in cervical spondylosis (CS) patients by observing the effects of tuina manipulation on the three-dimensional (3D) angles. METHODS: From August to December 2009 20 CS patients were assigned to Group 1 (10 cases, treated with relaxing manipulation) and Group 2 (10 cases, treated with relaxing manipulation and joint regulation). Besides, 10 healthy subjects were recruited as the normal group (treated with relaxing manipulation). Before and after manipulation intervention, all of them were scanned from the base of the skull to the first thoracic vertebra using Philips 64 spiral CT under equal conditions, thus obtaining the volume data. The 0.625 mm thickness was reconstructed using ITK reconstruction software provided by the digital medical laboratory, Software College of Shanghai Jiaotong University. The reconstruction of each cervical skeleton was finished referring to CT data. Changes of the 3D angles were compared among the three groups. RESULTS: The regulation of the 3D C2 vertebra: Results of Group 2 were significantly larger than those of the normal group at X-, Y-, and Z-axis (P < 0.05). Results of Group 2 were significantly larger than those of Group 1 at X- and Z-axis (P < 0.05). But results of Group 1 were significantly larger than those of the normal group at Z-axis (P < 0.05). The regulation of the 3D C3 vertebra: Results of Group 2 were significantly larger than those of the normal group at X- and Y-axis (P < 0.05). Results of Group 2 were significantly larger than those of Group 1 at X-axis (P < 0.05). But results of Group 1 were significantly larger than those of the normal group at X-axis (P < 0.05). The regulation of the 3D C4 vertebra: Results of Group 2 were significantly larger than those of the normal group at X- and Y-axis (P < 0.05). Results of Group 2 were significantly larger than those of Group 1 at X- and Z-axis (P < 0.05). There were no significant difference among the three groups in the 3D spaces of C1, C5, C6, and C7. The larger 3D space was shown in Group 2 than in Group 1 and the normal group. CONCLUSIONS: The relaxing manipulation combined with joint regulation significantly improved the 3D angles of C2, C3, and C4 in CS patients. The mechanism of tuina manipulation for treating the dislocation of bone in CS patients might lie in adjusting the 3D space of the cervical spine, and improving its functions.

Electrochemical behavior of Mg electrode in sodium salt electrolyte system.

A suitable electrolyte is crucial to enhancing the electrochemical performance of magnesium (Mg) batteries. Here, the influence of Na2SiO3 on the electrochemical behavior of AZ31B Mg alloy in the Na2SO4-NaNO3 composite electrolyte was investigated. The results revealed that the activation potential of the AZ31B Mg alloy first represented a negative shift and then a positive shift with the increase in Na2SiO3. The most negative activation potential (-1.51 V) and the lowest polarization (-3.20 V) were found when 6 mM of Na2SiO3 was added; no discharge hysteresis was observed, and the polarization resistance value (R 1) was 3,806 Ω. After 24 h immersion in the composite electrolyte with Na2SiO3, more and wider cracks appeared on the alloy surface, where a thick, dense film was formed, showing excellent discharge performance and corrosion resistance.

Yijinjing Qigong intervention shows strong evidence on clinical effectiveness and electroencephalography signal features for early poststroke depression: A randomized, controlled trial.

Objective: Although Traditional Chinese Yijinjing Qigong Exercise (YJJQE) as mind-body intervention is popularly used among adults to ameliorate depressive symptoms in China, no randomized controlled trials (RCTs) are available to evaluate the effects of YJJQE in patients with poststroke depression (PSD). This study aims to explore the clinical efficacy and the neurological and psychiatric mechanism in brain network functional connectivity underlying electroencephalography (EEG). Materials and methods: A total of 60 patients, diagnosed with mild PSD, were randomly (1:1) assigned to YJJQE group (n = 30) and control group of routine segmental rehabilitation training group (n = 30) for a 60-min exercise session once a day for 3 weeks. All outcome measures were collected at baseline and 3-weeks ending intervention. The primary outcome was the 24-item Hamilton Depression Scale (HAMD-24) score, evaluation at more time points for 1 month of follow-up. The secondary outcomes were EEG data in four frequency domains (δ, θ, α, and ß), global efficiency (GE), local efficiency (LE), GE/LE curve [areas under the curve (AUC)], Phase Lag Index (PLI), (HAMD-24) Score and EEG correlation analysis. Results: All patients showed no significant differences in baseline data. After 3 weeks and 1 month of follow-up, the YJJQE group demonstrated significant decreasing changes compared to the control group on the HAMD-24 scores (p < 0.001). Furthermore, the YJJQE group also showed a significant reduction in θ wave, and an increase in both GE and LE. Compared to the control group, the YJJQE Qigong group showed significantly greater functional connectivity in the δ, θ, and ß frequency bands in the brain network of the degree of phase synchronization (p < 0.001). HAMD-24 Score and EEG correlation analysis negative correlation in the Qigong group θ wave (p < 0.001). Conclusion: Our findings demonstrated that YJJQE is estimated to effectively alleviate the depressed mood of patients with PSD by promoting the efficiency in information transmission of network functional connectivity and its integration ability in different brain regions. Therefore, the YJJQE would be useful as a non-pharmacological treatment to prevent PSD. Clinical trial registration: [http://www.chictr.org.cn/showproj.aspx?proj=55789], identifier [ChiCTR2000035588].

Cerebral mechanism of Tuina analgesia in management of knee osteoarthritis using multimodal MRI: study protocol for a randomised controlled trial.

BACKGROUND: The chronic pain of patients with knee osteoarthritis (KOA) seriously affects their quality of life and leads to heavy social and economic burden. As a nondrug therapy in Traditional Chinese Medicine (TCM), Tuina is generally recognised as safe and effective for reducing the chronic pain of KOA. However, the underlying central mechanisms of Tuina for improving the pain of KOA are not fully understood. METHODS/DESIGN: This study will be a randomised controlled trial with a parallel-group design. A total of 60 eligible participants will be assigned to the Tuina group or healthcare education group (Education group) at 1:1 ratio using stratified randomisation with gender and age as factors. The interventions of both groups will last for 30 min per session and be conducted twice each week for 12 weeks. This study will primarily focus on pain evaluation assessed by detecting the changes in brain grey matter (GM) structure, white matter (WM) structure, and the cerebral functional connectivity (FC) elicited by Tuina treatment, e.g., thalamus, hippocampus, anterior cingulate gyrus, S1, insula, and periaqueductal grey subregions (PAG). The two groups of patients will be evaluated by clinical assessments and multimodal magnetic resonance imaging (MRI) to observe the alterations in the GM, WM, and FC of participants at the baseline and the end of 6 and 12 weeks' treatment and still be evaluated by clinical assessments but not MRI for 48 weeks of follow-up. The visual analogue scale of current pain is the primary outcome. The Short-Form McGill Pain Questionnaire, Western Ontario and McMaster Universities Osteoarthritis Index, 36-Item Short Form Health Survey, Hamilton Depression Scale, and Hamilton Anxiety Scale will be used to evaluate the pain intensity, pain feeling, pain emotion, clinical symptoms, and quality of life, respectively. MRI assessments, clinical data evaluators, data managers, and statisticians will be blinded to the group allocation in the outcome evaluation procedure and data analysis to reduce the risk of bias. The repeated measures analysis of variance (2 groups × 6 time points ANOVA) will be used to analyse numerical variables of the clinical and neuroimaging data obtained in the study. P<0.05 will be the statistical significance level. DISCUSSION: The results of this randomised controlled trial with clinical assessments and multimodal MRI will help reveal the influence of Tuina treatment on the potential morphological changes in cortical and subcortical brain structures, the white matter integrity, and the functional activities and connectivity of brain regions of patients with KOA, which may provide scientific evidence for the clinical application of Tuina in the management of KOA. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000037966 . Registered on Sep. 8, 2020. DISSEMINATION: The results will be published in peer-reviewed journals and disseminated through the study's website, and conferences.

Effect of traditional Chinese manual therapy on alleviating pain and dysfunction of lumbar disc herniation: a randomized controlled pilot study.

OBJECTIVE: To investigate the effect of traditional Chinese manual therapy (TCMT) in alleviating pain and dysfunction in patients with lumbar disc herniation (LDH). METHODS: Sixty-six patients with LDH were recruited as the study cohort and randomly assigned to an observation group and a control group. The patients in the observation group underwent TCMT, whereas those in the control group underwent conventional lumbar traction (LT). The observed indexes comprised primary index, which referred to clinical efficacy, and secondary indexes, which include Simplified McGill Pain Questionnaire, Oswestry Disability Index (ODI), range of motion (ROM) of the lumbar spine, difference in muscle tone (MT) and pressure pain threshold (PPT) of the bilateral erector spinae, and serum inflammatory factor levels. RESULTS: The total effective rate was significantly higher in the observation group than in the control group (96.67% vs. 66.67%, P < 0.001). Compared with the control group after treatment, patients in the observation group had significantly lower ODI, pain rating index, visual analog scale and present pain intensity scores (all P < 0.05), and had significantly smaller differences in MT and PPT of the bilateral erector spinae (both P < 0.001), but had remarkably greater ROM of the lumbar spine (P < 0.001). In addition, interleukin (IL)-6, IL-8, and interferon-γ concentrations in the observation group were significantly lower than those in the control group after treatment (all P < 0.05). CONCLUSION: TCMT has positive effects on alleviating pain and improving dysfunction of patients with LDH and helps in reducing serum inflammatory factor levels.

Effectiveness and functional magnetic resonance imaging outcomes of Tuina therapy in patients with post-stroke depression: A randomized controlled trial.

Objective: To investigate the effectiveness and functional magnetic resonance imaging (fMRI) outcomes of Tuina therapy in patients with post-stroke depression (PSD). Methods: This was a single-center, randomized, two-armed, controlled trial. Eighty-four patients with PSD were selected and randomly assigned to a Tuina therapy group or a routine rehabilitation control group. The patients underwent five 20-min treatment sessions per week over a period of 2 weeks. The primary outcome measure was change in Hamilton Depression Rating Scale (HAMD) score over the 2 weeks of intervention, whereas the secondary outcome measures were changes in Fugl-Meyer Assessment (FMA) score, Modified Barthel index (MBI), and Mini Mental State Examination (MMSE) score. Results: The Tuina group showed significantly improved HAMD scores compared to the routine rehabilitation control group (5.85, [2.54, 9.16]). For the secondary outcomes, the Tuina group showed better MMSE scores than the routine rehabilitation group (1.97, [1.19, 2.76]); however, there were no significant differences between the other secondary outcomes of both groups (P > 0.05). After 2 weeks, both groups showed a significant decrease in HAMD score compared to baseline. In addition, the Tuina group showed a significant decrease in MMSE score compared to baseline (2.35, [1.8, 2.9]); however, there were no significant differences in the MBI and FMA scores of the two group after the intervention (P > 0.05). Regarding fMRI results, the zALFF values of the right caudate nucleus, right putamen, right insula, left superior temporal gyrus, right parahippocampal gyrus, right hippocampus, left middle temporal gyrus, left angular gyrus, and left thalamus were higher in the Tuina group. In the Tuina group, the functional connectivity between the hippocampus and thalamus, and the thalamus and caudate nucleus, were significantly different (P <0.01). In addition, the zALFF value of the hippocampus was significantly negatively correlated with HAMD score. No serious adverse events were observed in both groups. Conclusion: Tuina therapy administered 10 times within 2 weeks is safe and can effectively relieve depression and improve cognitive function in patients with PSD. This finding may be closely related to the effect of Tuina therapy on the activation and functional connectivity of the hippocampus. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=55151, identifier ChiCTR200003388.

Manual therapy regulates oxidative stress in aging rat lumbar intervertebral discs through the SIRT1/FOXO1 pathway.

With the increasing burden of a globally aging population, low back pain has become one of the most common musculoskeletal disorders, caused mainly by intervertebral disc (IVD) degeneration. There are currently several clinical methods to alleviate back pain, but there is scarce attention paid as to whether they can improve age-related IVD degeneration. It is therefore difficult to conduct an in-depth evaluation of these methods. A large number of clinical studies have shown that manual therapy (MT), a widely used comprehensive alternative method, has effects on pain, the mechanisms of which require further study. In this study, MT was performed on aging rats for 6 months, and their behaviors were compared with those of a non-intervention group of aging and young rats. After the intervention, all rats were examined by X-ray to observe lumbar spine degeneration, and the IVD tissues were dissected for detection, including pathological staining, immunofluorescence, Western bolt, etc. This study demonstrated the possibility that MT intervention delay the lumbar IVD degeneration in aging rats, specifically improving the motor function and regulating senescence-associated ß-galactosidase, p53, p21, p16, and telomerase activity to retard the senescence of cells in IVDs. Moreover, MT intervention can modify oxidative stress, increase the expression of SIRT1 and FOXO1 in IVDs and decrease ac-FOXO1 expression, suggesting that MT can reduce oxidative stress through the SIRT1/FOXO1 pathway, thereby playing a role in delaying the aging of IVDs. This study shows that drug-free, non-invasive mechanical interventions could be of major significance in improving the physical function of the elderly.

Effect of traditional Chinese exercise combined with massage on pain and disability in patients with lumbar disc herniation: A multi-center, randomized, controlled, assessor-blinded clinical trial.

Background: Herniation of the nucleus pulposus caused by disc degeneration and other reasons can cause low back pain and disability. In China, traditional Chinese exercises (TCEs) and traditional Chinese massage (TCM) are widely used to improve symptoms of pain and disability in patients with lumbar disc herniation (LDH). The safety and efficacy of combination therapy have not been studied. Objectives: To assess the effect of traditional Chinese exercise combined with massage vs. traditional Chinese massage alone on pain, disability, lumbar mobility and gait performance in patients with LDH. Methods: Multi-center, randomized clinical trial conducted at 4 hospitals in China and enrolling 272 patients with LDH. Participants were randomly assigned to TCEs plus TCM group or TCM alone group. The combined therapy group received 18 Tai Chi training sessions (30-min sessions 3 times a week) and regular TCM treatments over 6 weeks. The control group received TCM therapy alone and was instructed to maintain their usual daily physical activity. Outcome variables measured included Visual Analog Scale (VAS), Short Form of McGill Pain Questionnaire (SF-MPQ), Oswestry Disability Index (ODI), lumbar spine range of motion (ROM) and gait performance. Results: Among the 272 randomized participants, 259 completed the study. The mean VAS score was 51.77 mm at baseline in the TCEs plus TCM group, and 50.93 mm for the TCM alone group. The reduction in the VAS score at week 6 was greater in the TC group than in the TCM group with a mean difference of 4.05 (95% CI, 2.15-5.95; P < 0.001), and the ODI score with between-group differences of 3.57 points (95% CI, 2.84-4.30 points; P < 0.001). Similar significantly different results were observed in SF-MPQ, walking speed, cadence, and lumbar ROM. No serious adverse events were reported throughout the study period. Conclusion: Compared with TCM alone, TCEs combined with TCM treatment performed better in reducing pain and improving disability. The combination therapy could be considered a valuable treatment option for LDH patients, with potential therapeutic utility for middle-aged and elderly patients with LDH.

The Effectiveness of Traditional Chinese Yijinjing Qigong Exercise for the Patients With Knee Osteoarthritis on the Pain, Dysfunction, and Mood Disorder: A Pilot Randomized Controlled Trial.

Background: Although traditional Chinese Yijinjing Qigong Exercise (YJJQE) is popularly used in China, to alleviate symptoms of people with knee osteoarthritis (KOA), no randomized controlled trials (RCTs) are available to evaluate the effects of YJJQE in patients with KOA. The purpose of this trial is to assess the clinical efficacy of YJJQE for patients with KOA. Methods: A total of 50 participants clinically diagnosed with KOA are randomly (1:1) assigned to the YJJQE group (n = 25) and to the stretching training exercise (STE) group (n = 25), for a 40-min exercise session twice a week for 12 weeks. All outcome measures are collected at baseline and at 12-week ending intervention, which includes the primary outcomes of Western Ontario and McMaster Universities Osteoarthritis Index Scale (WOMAC), the secondary outcomes of visual analog scale (VAS), mental component summary (MCS), physical component summary (PCS), Beck depression inventory (BDI), perceived stress scale (PSS), Berg balance scale (BBS), and the Gait functional mobility data. Results: The YJJQE group did not have any significant changes compared to the control group on the WOMAC score after the 12-week intervention (P > 0.05), though the YJJQE group demonstrated better performance in MCS, BDI, and PSS (P = 0.002, P = 0.001, and P = 0.026, respectively) than the control group. No serious adverse events occurred in either group, and only mild muscle soreness was reported during both exercise treatments. Conclusion: Because no difference between both groups was shown, with regards to the primary outcome measurement (WOMAC), it can hardly explain that the YJJQE had an advantageous effect on patients experiencing the pain and dysfunction of knee osteoarthritis. However, compared to the control group, YJJQE appeared to be associated with improvements in psychological well-being including reduced stress, anxiety, depression, and mood disturbance to manage KOA. Further trials with larger sample sizes and follow-up studies will be required. Clinical Trial Registration: https://www.chictr.org.cn/edit.aspx?pid=60357&htm=4, ChiCTR2000037256.