Study protocol for a randomized controlled trial: evaluating the effect of isokinetic eccentric training of the hamstring on knee function and walking function after total knee arthroplasty.

Introduction: Total knee arthroplasty (TKA) is a widely-used treatment for end-stage knee osteoarthritis. However, it is common for patients to experience issues with knee joint function and abnormal gait following the surgery. Previous studies have primarily focused on concentric contraction of the quadriceps during TKA, neglecting the potential benefits of eccentric isokinetic training for the hamstrings. This protocol outlines a randomized, single-blind, controlled trial aimed at assessing the impact of eccentric isokinetic training for the hamstring muscles on pain, function, and gait in patients after TKA. Methods and analysis: Fifty participants between the ages of 50 and 80 with knee osteoarthritis undergo unilateral total knee arthroplasty (TKA) for the first time. They will be transferred to the rehabilitation department 10-14 days after the operation. The participants are randomly divided into two groups, with 25 participants in each group: the control group and the Hamstring training group. The Control group will receive routine rehabilitation treatment, while the Hamstring training group will receive a combination of routine rehabilitation treatment and isokinetic eccentric training of the hamstring. The intervention will last four consecutive weeks. Both groups will be assessed at three different times: before the intervention, after 4 weeks of intervention, and 4 weeks after the interventions (follow-up). The primary outcome will be functional capacity (TUGT) and Hospital for Special knee Score (HSS). Secondary outcomes will be knee-related health status (isokinetic knee position perception, Peak torque of hamstring strength), pain intensity (Visual analog scale, VAS) and 3D gait analysis. Discussion: The study aims to provide relevant evidence on the effectiveness of eccentric hamstring muscle contraction training in improving knee joint function and walking function after TKA. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=195544, Identifier ChiCTR2300073497.

Role of long Intergenic Nonprotein-Coding RNA 00511 in Nod-Like Receptor Protein Pyrin Domain 3-Induced Chondrocyte Pyroptosis via the MicroRNA-9-5p/FUT1 Axis.

This study aimed to determine the function of LINC00511 in NLRP3 inflammasome-mediated chondrocyte pyroptosis via the regulation of miR-9-5p and FUT 1. Chondrocyte inflammatory injury was induced by treating chondrocytes with LPS. Afterwards, the levels of IL-1ß and IL-18, the expression of NLRP3, ASC, Caspase-1, and GSDMD, cell viability, and LDH activity in chondrocytes were assessed. LINC00511 expression in LPS-treated chondrocytes was detected, and LINC00511 was subsequently silenced to analyse its role in chondrocyte pyroptosis. The subcellular localization of LINC00511 was predicted and verified. Furthermore, the binding relationships between LINC00511 and miR-9-5p and between miR-9-5p and FUT1 were validated. LINC00511 regulated NLRP3 inflammasome-mediated chondrocyte pyroptosis through the miR-9-5p/FUT1 axis. LPStreated ATDC5 cells exhibited elevated levels of inflammatory injury; increased levels of NLRP3, ASC, Caspase-1, and GSDMD; reduced cell viability; increased LDH activity; and increased LINC00511 expression, while LINC00511 silencing inhibited the NLRP3 inflammasome to restrict LPS-induced chondrocyte pyroptosis. Next, LINC00511 sponged miR-9-5p, which targeted FUT1. Silencing LINC00511 suppressed FUT1 by upregulating miR-9-5p. Additionally, downregulation of miR-9-5p or overexpression of FUT1 neutralized the suppressive effect of LINC00511 knockdown on LPSinduced chondrocyte pyroptosis. Silencing LINC00511 inhibited the NLRP3 inflammasome to quench Caspase-1-dependent chondrocyte pyroptosis in OA by promoting miR-9-5p and downregulating FUT1.

Diaphragmatic breathing combined with abdominal drawing-in maneuver for walking function in post-stroke patients: a randomized controlled study protocol.

BACKGROUND: Patients with stroke frequently experience walking dysfunction. Core training can help improve balance and walking function in patients with stroke. However, core training movements in clinical practice are numerous and differently targeted. Therefore, this study will investigate the improvement of walking function in patients with combined diaphragmatic breathing maneuver (DBM) and draw-in breathing technique (ADIM) training. METHODS: This single-blind, randomized controlled preliminary will analyze the viability of DBM combined ADIM training versus routine rehabilitation therapy in patients with stroke with early to mid-stroke. Patients will be randomly assigned to either the DBM and ADIM training or the routine rehabilitation training. We will recruit 42 stroke inpatients from the Second Rehabilitation Hospital of Shanghai who meet the trial criteria and measure the balance and walking functions and improvement of that after 4 weeks of intervention. The primary outcome is the 10 m maximum walking test (10MWT). The secondary outcomes indices include the limits of stability test (LOS), Berg balance scale test (BBS), Functional Ambulation Categories test (FAC), Timed Up and Go test (TUG), trunk impairment scale test (TIS), ultrasound indicators of the diaphragm and transversus abdominis (UI), rhythmic weight shift test (RWS), walk across test (WA), Fugl-Meyer assessment of lower extremity (FMA-LE), and Barthel index of ADL test. DISCUSSION: The primary objective of this project was to investigate the effects of DBM combined with ADIM on balance capacity and walking function for patients with early to mid-stroke. The outcomes of this study will hold significant implications for future clinical applications in rehabilitation. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ID: ChiCTR2100054897. Registered on 28 December 2021.

Effect of music-based movement therapy on the freezing of gait in patients with Parkinson's disease: A randomized controlled trial.

Background: Progression of freezing of gait (FOG), a common pathological gait in Parkinson's disease (PD), has been shown to be an important risk factor for falls, loss of independent living ability, and reduced quality of life. However, previous evidence indicated poor efficacy of medicine and surgery in treating FOG in patients with PD. Music-based movement therapy (MMT), which entails listening to music while exercising, has been proposed as a treatment to improve patients' motor function, emotions, and physiological activity. In recent years, MMT has been widely used to treat movement disorders in neurological diseases with promising results. Results from our earlier pilot study revealed that MMT could relieve FOG and improve the quality of life for patients with PD. Objective: To explore the effect of MMT on FOG in patients with PD. Materials and methods: This was a prospective, evaluator-blinded, randomized controlled study. A total of 81 participants were randomly divided into music-based movement therapy group (MMT, n = 27), exercise therapy group (ET, n = 27), and control group (n = 27). Participants in the MMT group were treated with MMT five times (1 h at a time) every week for 4 weeks. Subjects in the ET group were intervened in the same way as the MMT group, but without music. Routine rehabilitation treatment was performed on participants in all groups. The primary outcome was the change of FOG in patients with PD. Secondary evaluation indicators included FOG-Questionnaire (FOG-Q) and the comprehensive motor function. Results: After 4 weeks of intervention, the double support time, the cadence, the max flexion of knee in stance, the max hip extension, the flexion moment of knee in stance, the comprehensive motor function (UPDRS Part III gait-related items total score, arising from chair, freezing of gait, postural stability, posture, MDS-UPDRS Part II gait-related items total score, getting out of bed/a car/deep chair, walking and balance, freezing), and the FOG-Q in the MMT group were lower than that in the control group and ET group (p < 0.05). The gait velocity, the max ankle dorsiflexion in stance, ankle range of motion (ROM) during push-off, ankle ROM over gait cycle, the knee ROM over gait cycle, and the max extensor moment in stance (ankle, knee) in the MMT group were higher than that in the control group and ET group (p < 0.05). However, no significant difference was reported between the control group and ET group (p > 0.05). The stride length and hip ROM over gait cycle in the MMT group were higher than that in the control group (p < 0.05), and the max knee extension in stance in the MMT group was lower than that in the control group (p < 0.05). Nevertheless, there was no significant difference between the ET group and MMT group (p > 0.05) or control group (p > 0.05). Conclusion: MMT improved gait disorders in PD patients with FOG, thereby improving their comprehensive motor function.

Similarities and differences between rat and mouse chondrocyte gene expression induced by IL-1ß.

BACKGROUND: Osteoarthritis (OA) is the most prevalent degenerative joint disease. In vitro experiments are an intuitive method used to investigate its early pathogenesis. Chondrocyte inflammation models in rats and mice are often used as in vitro models of OA. However, similarities and differences between them in the early stages of inflammation have not been reported. OBJECTIVE: This paper seeks to compare the chondrocyte phenotype of rats and mice in the early inflammatory state and identify chondrocytes suitable for the study of early OA. METHODS: Under similar conditions, chondrocytes from rats and mice were stimulated using the same IL-1ß concentration for a short period of time. The phenotypic changes of chondrocytes were observed under a microscope. The treated chondrocytes were subjected to RNA-seq to identify similarities and differences in gene expression. Chondrocytes were labelled with EdU for proliferation analysis. Cell proliferation-associated proteins, including minichromosome maintenance 2 (MCM2), minichromosome maintenance 5 (MCM5), Lamin B1, proliferating cell nuclear antigen (PCNA), and Cyclin D1, were analysed by immunocytochemical staining, cell immunofluorescence, and Western blots to verify the RNA-seq results. RESULTS: RNA-seq revealed that the expression patterns of cytokines, chemokines, matrix metalloproteinases, and collagen were similar between the rat and mouse chondrocyte inflammation models. Nonetheless, the expression of proliferation-related genes showed the opposite pattern. The RNA-seq results were further verified by subsequent experiments. The expression levels of MCM2, MCM5, Lamin B1, PCNA, and Cyclin D1 were significantly upregulated in rat chondrocytes (P < 0.05) and mouse chondrocytes (P < 0.05). CONCLUSIONS: Based on the findings, the rat chondrocyte inflammation model may help in the study of the early pathological mechanism of OA.

Immediate Effect of Dry Needling at Myofascial Trigger Point on Hand Spasticity in Chronic Post-stroke Patients: A Multicenter Randomized Controlled Trial.

Background: Hand spasticity after stroke influences the rehabilitation of hand function. Immediate and effective relief of spasticity potentially creates conditions for later rehabilitation training, which has far-reaching significance in the smooth transition of patients to the recovery period. Objective: To evaluate the immediate effect of dry needling (DN) at myofascial trigger point on hand spasticity in stroke patients. Methods: This was a prospective, evaluator blind, multicenter, randomized controlled study. A total of 210 participants were randomly divided into DN group (DN, N = 70), sham dry needling group (SDN, N = 70), and control group (N = 70). Participants in the DN group were treated with DN at myofascial trigger point five times (30 min each time) every week for 4 weeks. Subjects in the SDN group were manipulated the same way as in the DN group, except that the acupuncture site was located in the area adjacent to the myofascial trigger point, which constituted a SDN. Routine rehabilitation treatment was performed for participants in the two groups and in the control group. The primary evaluation index was the immediate effect of hand spasticity relief. Secondary evaluation indicators included the cumulative effect of hand spasticity relief from baseline to week 4, and the changes in flexion angles of the wrist, thumb, and fingers 2-5 in the rest position before, immediately after, and 4 weeks after intervention. Results: The immediate effective rate of spasticity relief (thumb, fingers 2-5, and wrist) of patients with different degrees of spasticity in the DN group was higher than that in the control and SDN groups (thumb, χ2 = 55.833, P < 0.001; fingers 2-5, χ2 = 68.096, P < 0.001; wrist, χ2 = 49.180, P < 0.001) (P < 0.05). The effective rate of spasticity relief from baseline to 4 weeks in the DN group exceeded that in the control group and SDN groups (thumb, χ2 = 8.806, P = 0.012; fingers 2-5, χ2 = 8.087, P = 0.018; and wrist, χ2 = 8.653, P = 0.013) (P < 0.05). No difference in immediate and cumulative effect was found between the control group and SDN group. The change of joints flexion angles in resting position before and after each treatment in the DN group was higher than that in the control and SDN groups (P < 0.05), but it was not significantly different between the control group and SDN group. At 4 weeks, although the change in the DN group was higher than that in the control group and SDN group, this difference was not statistically significant (P > 0.05). Conclusion: Dry needling can relieve varying degrees of hand spasticity instantly in post-stroke. Trial Registration: www.chictr.org.cn, ChiCTR1900022379.

Improvement of freezing of gait in patients with Parkinson's disease by music exercise therapy: a study protocol for a randomized controlled trial.

BACKGROUND: Progression of freezing of gait, a common pathological gait in Parkinson's disease, is an important risk factor for diagnosing the disease and has been shown to predispose patients to easy falls, loss of independent living ability, and reduced quality of life. Treating Parkinson's disease with freezing of gait is very difficult, while the use of medicine and operation has been ineffective. Music exercise therapy, which entails listening to music as you exercise, has been proposed as a treatment technology that can change patients' behavior, emotions, and physiological activity. In recent years, music exercise therapy has been widely used in treatment of motor disorders and neurological diseases and achieved remarkable results. Results from our earlier pilot study revealed that music exercise therapy can improve the freezing of gait of Parkinson's patients and improve their quality of life. Therefore, we aim to validate clinical efficacy of this therapy on freezing of gait of Parkinson's patients using a larger sample size. METHODS/DESIGN: This three-arm randomized controlled trial will evaluate clinical efficacy of music exercise therapy in improving the freezing of gait in Parkinson's patients. We will recruit a total of 81 inpatients with Parkinson's disease, who meet the trial criteria. The patients will randomly receive music exercise with and without music as well as routine rehabilitation therapies, followed by analysis of changes in their gait and limb motor function after 4 weeks of intervention. We will first use a three-dimensional gait analysis system to evaluate changes in patients' gait, followed by assessment of their limb function, activity of daily living and fall risk. DISCUSSION: The findings of this trial are expected to affirm the clinical application of this therapy for future management of the disease. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900026063 . Registered on September 20, 2019.

MEK1/2 Inhibitor (GDC0623) Promotes Osteogenic Differentiation of Primary Osteoblasts Inhibited by IL-1ß through the MEK-Erk1/2 and Jak/Stat3 Pathways.

OBJECTIVE: We evaluated the effects and mechanisms of GDC0623 on osteogenic differentiation of osteoblasts induced by IL-1ß. Methodology. Osteoblasts were treated with 20 ng/ml IL-1ß and 0.1 µM GDC0623. Cell proliferation levels were evaluated by the cell counting kit 8 (CCK8), EdU assay, and western blotting [proliferating cell nuclear antigen (PCNA) and Cyclin D1]. Osteoblasts were cultured in an osteogenic induction medium for 1-3 weeks after which their differentiations were assessed by alkaline phosphatase (ALP) staining, Alizarin Red staining, calcium concentration, immunocytochemistry staining, real-time quantitative PCR (RT-qPCR), and immunofluorescence staining. The osteogenesis-associated mechanisms were further evaluated by western blotting using appropriate antibodies. RESULTS: Relative to the control group, IL-1ß induced the rapid proliferation of osteoblasts and suppressed their osteogenic differentiations by upregulating the activities of MEK-Erk1/2 as well as Jak-Stat3 pathways and by elevating MMP13 and MMP9 levels. However, blocking of the MEK-Erk1/2 signaling pathway by GDC0623 treatment reversed these effects. CONCLUSION: Inhibition of Jak-Stat3 pathway by C188-9 downregulated the expression levels of MMP9 and MMP13, activated MEK-Erk1/2 pathway, and inhibited osteogenic differentiation.

Acupuncture of fascia points to relieve hand spasm after stroke: a study protocol for a multicenter randomized controlled trial.

BACKGROUND: The loss of functional ability of patients after stroke is mostly caused by dysfunction of the upper limbs, especially the hands. Hand functional exercise is the premise of alleviating hand dysfunction, and the relief of hand spasm is the basis of timely and effective hand functional exercise. Previous clinical observation have shown that fascial-point needling can effectively alleviate hand spasm immediately after stroke, but further evidence from large-sample studies is needed. The overall objective of this trial is to further evaluate the clinical efficacy of fascial-point acupuncture on hand spasm after stroke. METHODS/DESIGN: This multicenter randomized controlled trial will compare the efficacy of fascial-point acupuncture versus sham acupuncture and routine rehabilitation therapy in stroke patients with hand spasm. Patients will be randomized to undergo either the fascial-point acupuncture, the sham acupuncture or the control (routine rehabilitation therapy). We will recruit 210 stroke inpatients who meet the trial criteria and observe the remission of hand spasm and improvement of limb function after 4 weeks of intervention. The first evaluation indices are the remission of hand spasm and the duration of spasm remission. The second evaluation indices are the hand function of the affected limbs and the activities of daily living. When the accumulative total number of cases included reaches 120, a mid-term analysis will be conducted to determine any evidence that experimental intervention does have an advantage. DISCUSSION: Our aim is to evaluate the efficacy of fascial-point acupuncture in relieving hand spasm after stroke. The results should provide more evidence for the clinical application of this therapy in the future. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ID: ChiCTR1900022379. Registered on 9 April 2019.

Effects of tai chi on physiology, balance and quality of life in patients with type 2 diabetes: A systematic review and meta-analysis.

OBJECTIVE: To systematically synthesize and critically evaluate evidence on the effects of tai chi for patients with type 2 diabetes mellitus. DATA SOURCES: Seven electronic databases (Wan Fang, SinoMed, China National Knowledge Infrastructure, VIP, PubMed, Embase, and Cochrane Library) were systematically searched from their inception to March 2018. STUDY SELECTION: Randomized controlled trials investigating the effects of tai chi on individuals with type 2 diabetes mellitus were eligible. DATA EXTRACTION: Biomedical outcomes (fasting plasma glucose, glycosylated haemoglobin (HbA1c), fasting insulin, insulin resistance, body mass index, total cholesterol, blood pressure) as well as balance and quality of life-related outcomes were extracted independently by 2 reviewers. Stata 12.0 software was used to synthesize data if there was no or moderate heterogeneity across studies. Otherwise, narrative summaries were performed. DATA SYNTHESIS: A total of 23 studies (25 articles) involving 1,235 patients were included in this meta-analysis. Significant changes in tai chi-related effects were observed in lowering fasting plasma glucose (standardized mean difference; SMD -0.67; 95% confidence interval (95% CI) -0.87 to -0.47; p <0.001), HbA1c (mean difference; MD-0.88%; 95% CI -1.45% to -0.31%; p =0.002) and insulin resistance (MD -0.41; 95% CI -0.78 to -0.04; p = 0.029). Beneficial effects of tai chi were also found in decreasing body mass index (MD -0.82 kg/m2; 95% CI -1.28 to -0.37 kg/m2; p < 0.001) and total cholesterol (SMD -0.59; 95% CI -0.90 to -0.27; p < 0.001). In addition, tai chi reduced blood pressure (systolic blood pressure (MD -10.03 mmHg; 95% CI -15.78 to -4.29 mmHg; p = 0.001), diastolic blood pressure (MD -4.85 mmHg; 95% CI -8.23 to -1.47 mmHg; p = 0.005)) and improved quality of life-related outcomes (physical function (MD 7.07; 95% CI 0.79-13.35; p = 0.027), bodily pain (MD 4.30; 95% CI 0.83-7.77; p = 0.015) and social function (MD 13.84; 95% CI 6.22-21.47; p < 0.001)). However, no impact was exerted on fasting insulin (SMD -0.32; 95% CI -0.71 to 0.07; p = 0.110) or balance (MD 2.71 s; 95% CI -3.29 to 8.71 s; p = 0.376). CONCLUSION: Tai chi is effective in controlling biomedical outcomes and improving quality of life-related outcomes in individuals with type 2 diabetes mellitus, although no effects were observed on balance and fasting insulin. Further high-quality research is needed to elucidate the effects of different types of tai chi, the long-term effects of tai chi, the impact on respiratory function, and the association between tai chi and the risk of developing type 2 diabetes mellitus in healthy individuals.

The Association between Toxoplasma gondii Infection and Risk of Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Several studies have investigated the association between Toxoplasma gondii (T. gondii) infection and risk of Parkinson's disease (PD) with inconsistent results. Clarifying this relation might be useful for better understanding of the risk factors and the relevant mechanisms of PD, thus a meta-analysis was conducted to explore whether exposure to T. gondii is associated with an increased risk of PD. METHODS: We conducted this meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A rigorous literature selection was performed by using the databases of PubMed, Embase, Web of Science, Cochrane Library, and ScienceDirect. Odds ratio (OR) and corresponding 95% confidential interval (CI) were pooled by using fixed-effects models. Sensitivity analysis, publication bias test, and methodological quality assessment of studies were also performed. RESULTS: Seven studies involving 1086 subjects were included in this meta-analysis. Pooled data by using fixed-effects models suggested both latent infection (OR, 1.17; 95% CI, 0.86 to 1.58; P=0.314) and acute infection (OR, 1.13; 95% CI, 0.30 to 4.35; P=0.855) were not associated with PD risk. Stable and robust estimates were confirmed by sensitivity analysis. No publication bias was found by visual inspection of the funnel plot, Begg's, and Egger's test. CONCLUSIONS: This meta-analysis does not support any possible association between T. gondii infection and risk of PD. Researches are still warranted to further explore the underlying mechanisms of T. gondii in the pathogenesis of PD and their causal relationship.

The Association Between Vitamin D Status, Vitamin D Supplementation, Sunlight Exposure, and Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND This literature review and meta-analysis aimed to determine the association between deficiency of vitamin D, or 25-hydroxyvitamin D, and Parkinson's disease, and whether vitamin D from supplements and sunlight improves the symptoms of Parkinson's disease. MATERIAL AND METHODS A literature review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Systematic literature review was performed using databases that included the Web of Science, PubMed, the Cochrane Library, and Embase. The Jadad scale (the Oxford quality scoring system) and the Newcastle-Ottawa scale (NOS) were used to evaluate the quality of the studies. RESULTS Eight studies were included in the meta-analysis. Both 25-hydroxyvitamin D insufficiency (<30 ng/mL) (OR, 1.77; 95% CI, 1.29-2.43; P<0.001) and deficiency (<20 ng/mL) (OR, 2.55; 95% CI, 1.98-3.27; P<0.001) were significantly associated with an increased risk of Parkinson's disease when compared with normal controls Sunlight exposure (³15 min/week) was significantly associated with a reduced risk of Parkinson's disease (OR, 0.02; 95% CI, 0.00-0.10; P<0.001). The use of vitamin D supplements was effective in increasing 25-hydroxyvitamin D levels (SMD, 1.79; 95% CI, 1.40-2.18; P<0.001), but had no significant effect on motor function (MD, -1.82; 95% CI, -5.10-1.45; P=0.275) in patients with Parkinson's disease. CONCLUSIONS Insufficiency and deficiency of 25-hydroxyvitamin D and reduced exposure to sunlight were significantly associated with an increased risk of Parkinson's disease. However, vitamin D supplements resulted in no significant benefits in improving motor function for patients with Parkinson's disease.