Zeolitic imidazole framework-8 loaded gelatin methacryloyl microneedles: A transdural and controlled-release drug delivery system attenuates neuroinflammation after spinal cord injury.

Spinal cord injury (SCI) is a matter of significant clinical concern, often treated through early surgical decompression along with methylprednisolone sodium succinate (MPSS). However, the side effects and the unsatisfactory focal concentration of MPSS have limited its further applications. To address this limitation, herein, a versatile drug delivery system of zeolitic imidazole framework-8 (ZIF-8) and gelatin methacryloyl microneedles (GelMA MNs) was developed for stable, transdural, and controlled sustained release of drugs in SCI. The microneedles were used to create tiny pores in the dura mater, allowing for the direct administration of drugs into the spinal cord. ZIF-8 provided a secondary extended release once they were separated from the microneedles. To attenuate the neuroinflammation, MPSS was selected. Such a combination of ZIF-8 and GelMA MNs was able to prolong the release period of MPSS to five days. The system showed transdural capacity, reduction of M1 polarization, and decrease in NLRP3-positive inflammasome and proinflammatory cytokines. In vivo studies indicated that this novel drug delivery strategy could constrict the inflammatory microenvironment, reduce glial scar formation, and promote neural regeneration. Thus, this versatile drug delivery system provides an up-and-coming alternative for stable, transdural, and controlled sustained release of drugs to those suffering from SCI.

Prediction of knee joint pain in Tai Chi practitioners: a cross-sectional machine learning approach.

OBJECTIVE: To build a supervised machine learning-based classifier, which can accurately predict whether Tai Chi practitioners may experience knee pain after years of exercise. DESIGN: A prospective approach was used. Data were collected using face-to-face through a self-designed questionnaire. SETTING: Single centre in Shanghai, China. PARTICIPANTS: A total of 1750 Tai Chi practitioners with a course of Tai Chi exercise over 5 years were randomly selected. MEASURES: All participants were measured by a questionnaire survey including personal information, Tai Chi exercise pattern and Irrgang Knee Outcome Survey Activities of Daily Living Scale. The validity of the questionnaire was analysed by logical analysis and test, and the reliability of this questionnaire was mainly tested by a re-test method. Dataset 1 was established by whether the participant had knee pain, and dataset 2 by whether the participant's knee pain affected daily living function. Then both datasets were randomly assigned to a training and validating dataset and a test dataset in a ratio of 7:3. Six machine learning algorithms were selected and trained by our dataset. The area under the receiver operating characteristic curve was used to evaluate the performance of the trained models, which determined the best prediction model. RESULTS: A total of 1703 practitioners completed the questionnaire and 47 were eliminated for lack of information. The total reliability of the scale is 0.94 and the KMO (Kaiser-Meyer-Olkin measure of sampling adequacy) value of the scale validity was 0.949 (>0.7). The CatBoost algorithm-based machine-learning model achieved the best predictive performance in distinguishing practitioners with different degrees of knee pain after Tai Chi practice. 'Having knee pain before Tai Chi practice', 'knee joint warm-up' and 'duration of each exercise' are the top three factors associated with pain after Tai Chi exercise in the model. 'Having knee pain before Tai Chi practice', 'Having Instructor' and 'Duration of each exercise' were most relevant to whether pain interfered with daily life in the model. CONCLUSION: CatBoost-based machine learning classifier accurately predicts knee pain symptoms after practicing Tai Chi. This study provides an essential reference for practicing Tai Chi scientifically to avoid knee pain.

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.

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.

Efficacy of Liu-zi-jue in Patients with 2019 Novel Coronavirus Pneumonia (COVID-19): structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: Efficacy of conventional treatment plus the complementary therapy Liu-zi-jue (a mind-body exercise) to treat patients with mild COVID-19. TRIAL DESIGN: The study is a single-center 2 arm, randomized controlled trial with parallel-group design.

Efficacy of Tuina in patients with chronic low back pain: study protocol for a randomized controlled trial.

BACKGROUND: Low back pain is a common reason for medical care and carries a heavy social burden. The efficacy of Tuina or health care education for low back pain has been evaluated in previous systematic reviews. However, there is no evidence to support the superiority of one form of treatment over another. The aim of this study is to compare the efficacy of Tuina with health care education in the management of low back pain. METHODS/DESIGN: This study is a randomized controlled trial with parallel-group design including two groups: a Tuina group and a health care education group. A total of 160 eligible participants will be randomly assigned to the groups in a 1:1 ratio. The interventions of both groups will last for 20 min and be carried out twice each week for a period of 12 weeks. The primary outcome is the Oswestry Disability Index. The secondary outcomes include a visual analogue scale and the 36-item Short Form Health Survey. They will be assessed at baseline, at the end of the intervention every month, and during 6 months and 9 months of follow-up by repeated measures analysis of variance. The significance level is 5%. The safety of Tuina and health care education will be evaluated after each treatment session. This study will focus on the value of Tuina and health care education for low back pain and will highlight any differences in the efficacy of the treatments. DISCUSSION: This study will evaluate the efficacy and safety of Tuina intervention for low back pain, which could provide reliable evidence for clinical decision making for patients with low back pain. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900022656. Registered on 23 April 2019.

Efficacy of tuina in patients with chronic neck pain: study protocol for a randomized controlled trial.

BACKGROUND: Chronic neck pain (CNP) is a common and disabling musculoskeletal disorder in developing and developed countries. Previous studies have shown that tuina and traditional Chinese massage are effective treatments for patients with CNP. However, there is little evidence to support the use of one intervention over the other. The aim of this study is to compare the effects of tuina and traditional Chinese massage in the treatment of pain and disability in patients with CNP. METHODS/DESIGN: This is a multicenter, assessor- and analyst-blinded, randomized controlled trial with two parallel arms: a tuina group and a traditional Chinese massage group. A total of 356 eligible CNP patients will be randomly assigned to the groups in a 1:1 ratio. The intervention in the tuina group includes both structural and relaxation massage, while the traditional Chinese massage group will receive relaxation massage only. The interventions for both groups will last for 15 min and will be carried out three times a week for a period of 4 weeks. The primary outcome will be changes in the Northwick Park Neck Pain Questionnaire. Secondary outcomes will be measured by a visual analogue scale (VAS), the Neck Disability Index (NDI), and the 36-item Short-Form Health Survey (SF-36). The data will be analyzed at the baseline, at the end of the intervention, and during the 3 months of follow-up by repeated measures analysis of variance. The significance level is 5%. The safety of tuina and traditional Chinese massage will be evaluated after each treatment session. The results of this trial will help clarify the value of tuina and traditional Chinese massage as treatments for CNP and will highlight any differences in the efficacy of the treatments. DISCUSSION: The purpose of this trial is to determine whether tuina is more effective than traditional Chinese massage in adults with CNP. This trial will, therefore, contribute to providing a solid foundation for clinical treatment of CNP, as well as future research in massage therapy. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-INR-17013763 . Registered 8 December 2017.

Possible mechanism underlying analgesic effect of Tuina in rats may involve piezo mechanosensitive channels within dorsal root ganglia axon.

OBJECTIVE: To demonstrate the analgesic effect of Tuina mainly from mechanically sensitive ion channels in peripheral myelinated nerve fibers. METHODS: A total of 40 healthy and pathogen-free adult male Sprague-Dawley rats were used in the study [weight: (220.0 ¡À 1.4) g, Shanghai Slac Laboratory Animal Co., Ltd., Shanghai, China; license No. Shanghai ICP 05033115]. The rats were housed in cages with free access to water and food in a temperature-controlled room [(22 ¡À 1) ¡æ and 12-h/12-h light-dark cycle. Thirty-two rats were randomly divided into five groups: naive, sham, chronic compression of dorsal root ganglion (CCD), Tuina (7 d) and Tuina (21 d). CCD rat model was established via unilateral DRG compression by ""L"" liked steel bar. Chinese Tuina treatment was accepted once per day. Behavior monitoring of paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were tested. The expression of Piezo1 and Piezo2 in myelinated nerve fiber were analyzed by immunohistochemistry and Western-blotting. RESULTS: There was a high expression of Piezo2 and a low expression of Piezo1 in the naive and CCD groups. In contrast, the expression of Piezo2 was down regulated and Piezo1 was increased after a period of Tuina. There was significant difference (P¡Ü0.05) between the groups. CONCLUSION: Our findings suggest that Tuina therapy can increase the expression of Piezo2 and decrease the expression of Piezo1 in the test rats. The different changes in the expressions of Piezo1 and Piezo2 may play an important role in alleviating CCD-induced allodynia and hyperalgesia.

[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.

[Effects of early application of Tuina treatment on quadriceps surface myoelectricity in patients after total knee arthroplasty: a randomized controlled trial].

BACKGROUND: Total knee replacement surgery is commonly used in end-stage diseases of the knee. It is important for improving surgical efficacy and patient satisfaction by promoting early rehabilitation of patients and improving knee function. OBJECTIVE: To observe the effects of early application of Tuina treatment on quadriceps surface electromyography (EMG) in patients with rheumatoid arthritis having undergone total knee arthroplasty. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: The study was performed at the Orthopedic Department of Huashan Hospital, Fudan University, and the Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine from June 2010 to September 2011. A total of 66 patients with rheumatoid arthritis who had undergone total knee replacement surgery were randomly divided into control group and observation group, 33 cases in each. The patients in the control group were administered with continuous passive training (CPM), and the patients in the observation group were treated with CPM combined with Tuina, from prior surgery to four weeks post-surgery. MAIN OUTCOME MEASURES: The knee function was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire at baseline and 4 weeks after the surgery. Quadriceps surface EMG was also detected at the same time points. RESULTS: After 4 weeks of Tuina and comprehensive rehabilitation intervention, the WOMAC questionnaire score of the observation group was decreased compared with the control group (P<0.01); median frequency and integrated electromyography of the rectus femoris and vastus medialis muscles, which were recorded by EMG, in the observation group were higher than those in the control group (P<0.01). CONCLUSION: Tuina can improve the recovery of patients who have undergone total knee replacement by increasing quadriceps EMG.

[A review of evaluation scales for therapeutic effect of cervical spondylotic radiculopathy].

Various kinds of therapies have been clinically applied to treat cervical spondylotic radiculopathy (CSR). However, the evaluation standards of therapeutic effect in different medical institutions are quite different from each other at present, thus bringing about many difficulties in the therapeutic effect evaluation of CSR treatment. Although many CSR-related scales have been developed, none of them could completely represent or reflect the exact curative actualities of CSR in China. Therefore, it is quite essential to establish a comprehensive evaluation scale for the therapeutic effect of CSR. And such evaluation system, in which the estimation of quality of life should be included, will become the developmental direction of CSR research in future.

[Capillary blood flow with dynamical change of tissue pressure caused by exterior force].

A hemodynamic model of capillary and tissue, in which tissue pressure changed with swing manipulation of Traditional Chinese Medical Massage (TCMM), is presented in this paper to explain the hemodynamic mechanism of swing manipulation. Blood flowed in capillary with low Reynolds number. Plasma exuded through capillary according to the Starling's Law. Tissue pressure changed linearly with the massage force measured. Blood apparent viscosity, plasma protein concentration and red cell's hematocrit were taken into account. Capillary flow rate, blood apparent viscosity, filtration rate and filtration fraction with dynamical change of tissue pressure were calculated numerically, and were compared with those in static tissue pressure condition. Results showed that, dynamical change of tissue pressure led to the increase of capillary flow rate and the decrease of blood apparent viscosity, which qualitatively explained the hemodynamic mechanism of "promoting blood circulation and removing blood stasis" in swing manipulation of TCMM.