The purpose of this work is to investigate how the Rho family of GTPases A (RhoA) mediates the pathogenesis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). The expression of RhoA in the synovial tissues of RA and Healthy people (Control) was detected using immunohistochemistry methods. The expression of RhoA and hypoxia-inducible factor-1α (HIF-1α) is inhibited by small interfering RNAs (siRNAs). The inhibition effect on RA-FLS migration was further investigated. The protein expression level of HIF-1α, RhoA, focal adhesion kinase (FAK), and myosin light chain (MLC) was also analysed using western blotting (WB). DBA1 mice were immunised with the mixture of bovine type II collagen and Freund's adjuvant to establish collagen induced arthritis (CIA) mouse model. Lip-siRhoA is administered through joint injection every two days. Micro-computed tomography (micro-CT) was used to detect mouse ankle joint destruction and evaluate the bone loss of the periarticular side. Destruction of the ankle articular cartilage was tested by histology. Expressions of P-RhoA, P-FAK and P-MLC in the ankle joint was detected by immunohistochemistry assay. The expression level of RhoA in the synovial tissues of RA patients was significantly higher than that in control group. Hypoxia was able to up-regulate the expression of RhoA. Whereas, HIF-1α siRNA (siHIF-1α) could down-regulate the expression of RhoA. Additionally, both of siHIF-1α and RhoA siRNA (siRhoA) delivered by liposome (Lip-siHIF-1α and Lip-siRhoA) were found to suppress FAK and MLC phosphorylation in vitro. In CIA mouse model, Lip-siRhoA was demonstrated to ameliorate the destruction of ankle joint and reduce the severity of ankle joint cartilage damage by micro-CT and histological staining, respectively. Therefore, inhibition of FLS cell migration can protect articular bone from destruction. Furthermore, the expression of P-RhoA, P-FAK and P-MLC was evaluated and found to be down-regulated by Lip-siRhoA in vivo. The results demonstrated that under hypoxic environment, HIF-1α dependent RhoA pathway played an important role on cytoskeleton remodelling and RA-FLS migration. Through down-regulating RhoA expression, it could effectively treat RA in vitro and in vivo. Our study provides new evidence for the potential clinical application of RhoA as a candidate for the treatment of RA.

Objective: This study employed functional near-infrared spectroscopy (fNIRS) to systematically compare the effects of active movement (AM), passive movement (PM), and motor imagery (MI) on sensorimotor cortex excitability across three dimensions: spatial distribution, activation intensity, and temporal dynamics, thereby revealing distinct neural mechanisms underlying different motor therapies. Materials and methods: Sixteen healthy participants performed AM, PM, and MI tasks under therapist guidance using a block design. fNIRS data covered bilateral primary motor cortex (M1), primary somatosensory cortex (S1), supplementary motor area (SMA), dorsolateral prefrontal cortex (DLPFC), and frontopolar area (FPA). Analytical metrics included: (1) Spatial features: mean Δ [HbO] during 0–30s time windows; (2) Activation intensity: generalized linear model (GLM)-fitted Δ[HbO] during 0–30s; (3) Temporal dynamics: slope values during 2–7 s and T-centroid values during 0–60s. Results: Spatially, MI demonstrated the most extensive activation (bilateral DLPFC, SMA, M1, and left FPA; all p < 0.05, FDR-corrected), followed by AM (bilateral DLPFC, M1, and left FPA), while PM showed more limited activation (bilateral DLPFC, left S1, and right FPA). In activation intensity, AM exhibited significantly stronger activation than PM and MI in DLPFC channels 27 and 29 (both p < 0.05, uncorrected). Temporally, AM showed steeper slopes in left DLPFC channel 27 ( F = 10.31, p = 0.034, FDR-corrected), while MI demonstrated faster responses in right S1 and SMA (both p = 0.03, FDR-corrected), with both PM and MI responding faster than AM in left FPA ( p = 0.03, FDR-corrected). Conclusion: These findings reveal therapy-specific neural mechanisms: MI broadly engages motor execution and cognitive control networks through mental simulation, AM predominantly activates motor execution networks with DLPFC dominance, and PM recruits sensory-attentional networks via external facilitation. The multidimensional neuroimaging evidence provides a foundation for personalized rehabilitation protocols.

Tendinopathy is a common musculoskeletal disorder causing significant pain and functional impairment. High-intensity laser therapy (HILT) has increasingly been employed for tendinopathy. However, further research is required to elucidate therapeutic efficacy differences across various subtypes, determine optimal treatment parameters, and assess long-term effects. To evaluate the effectiveness of HILT for tendinopathy. PubMed, Embase, Cochrane Library, China Biology Medicine, Web of Science, CNKI, and SCOPUS databases were searched to include randomised controlled trials comparing HILT with placebo or other treatments up to 20 October 2025. Primary outcome measures included pain intensity and disability, analyzed as MD and SMD with 95% confidence intervals, respectively. Risk of bias was assessed using the Cochrane Tool and Physiotherapy Evidence Database scale. Heterogeneity was assessed with I², and random-effects models were used. 15 studies involving 629 patients were included: lateral epicondylitis (53%), rotator cuff tendinopathy (27%), and others (20%). Studies showed moderate quality (mean PEDro score 6.3), with strong randomisation (100% low risk) but weaknesses in allocation concealment (20% low risk) and blinding. HILT significantly improved pain (MD: -1.15; 95%CI: -1.73 to -0.58) and disability (SMD: -1.00; 95%CI: -1.77 to -0.22, p < 0.05). Pain reduction exceeded the MCID, though the lower confidence interval bound suggests marginal benefit in some. For disability, subgroup analysis by anatomical site revealed greater improvement in shoulder-related conditions (MD: -2.54) than in elbow-related conditions (MD: -0.91). Stress pain showed the most substantial relief (MD: -2.30), and treatment effects increased over time, peaking after 16 weeks. HILT effectively improves pain and disability in tendinopathy, with site-specific and cumulative benefits. Given methodological limitations, future high-quality studies are needed to optimize parameters and confirm long-term benefits.

Parkinson’s disease (PD) is a multifactorial neurodegenerative disease with a high prevalence worldwide, leading to motor and non-motor symptoms. Moreover, PD presents a progressive aggravation alongside time, the middle and late patients in PD requires the use of a variety of anti-Parkinson’s drugs with obvious side effects, which bring serious impact on the quality of life of patients. In recent years, repetitive transcranial magnetic stimulation (rTMS), as a kind of non-invasive neuromodulation therapy, has drawn increasing interest from neurologists, and has been effectively utilized to alleviate both motor and non-motor symptoms of PD. However, the treatment protocols and therapeutic effects of rTMS for PD patients are inconsistent. This meta-analysis aims to systematically evaluate the safety and efficacy of rTMS therapy in patients with PD. We will perform a comprehensive search in the following electronic databases: PubMed/Medline, Web of Science, EMBASE, and Cochrane, without language restrictions, from their inception to September 2024. This review protocol was formulated according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. The Cochrane risk of bias tool is utilized to assess the risk of bias. Finally, the effect size was expressed by a standardized mean difference (SMD) with a 95% confidence interval (CI). A total of 45 randomized controlled trials were included. The results of enrolled studies indicated that both primary and secondary indicators had improved. Subgroup analysis showed that high-frequency rTMS (HF-rTMS) targeting the supplementary motor area (SMD = − 0.56; 95 %CI = [−0.77, −0.36]; p < 0.00001), primary motor cortex (SMD: −1.65; 95 %CI = [−2.35, −0.95]; p < 0.00001), and dorsolateral prefrontal cortex (DLPFC) (SMD: −0.68; 95 %CI = [−1.16, −0.21]; p = 0.005) yielded a significant reduction in motor UPDRS-III scores, compared to the sham group. In addition, HF‐rTMS over left DLPFC or intermittent theta burst stimulation over left DLPFC may benefit cognition. Furtherly, the subgroup analysis of the Beck Depression Inventory scores indicated HF-rTMS over the left DLPFC was a beneficial treatment for depressive symptoms in PD. The meta-analysis showed that rTMS was effective and safe in the treatment of PD, improving motor function (such as a decrease in UPDRS-III total scores, subscores of UPDRS-III, and FOG-Q scores) in patients with PD and leading to improvement in cognitive function and depression (such as an increase in MocA scores and a decrease BDI scores). Although the results of the subgroup analysis provide a valuable reference for the selection of rTMS for clinical application, further larger multicenter, randomized, placebo-controlled studies with a large number of participants are still required to validate these results.

Background: The dorsolateral prefrontal cortex (DLPFC) plays a crucial role in cognitive-motor integration through its top-down regulation of the primary motor cortex (M1). However, the functional lateralization of the left and right DLPFC and the differences between intra-hemispheric and inter-hemispheric regulation of M1, particularly in populations with brain injury, remain controversial and insufficiently studied. Objective: This study aimed to systematically achieve the following four objectives using a dual-site paired-pulse transcranial magnetic stimulation (TMS) technique: (1) to evaluate the integrated regulatory effects of bilateral DLPFC on M1; (2) to compare the differences in regulatory effects between ipsilateral and contralateral DLPFC; (3) to analyze the impact of functional lateralization of the left and right DLPFC on their regulation of M1; (4) to investigate the effects of brain injury on the DLPFC-M1 regulatory pathway by comparing healthy participants and stroke patients. Methods: A total of 30 right-handed participants were enrolled, including 20 stroke patients in the recovery phase (divided into left and right lesion groups) and 10 healthy volunteers. These three participant groups were tested under conditions that varied the targeted motor cortex (M1) side, yielding four key experimental conditions for analysis. Accordingly, a paired-pulse TMS paradigm was employed. Following a conditioning stimulus (CS) applied to the left or right DLPFC, a test stimulus (TS) was delivered to the ipsilateral or contralateral M1 after an inter-stimulus interval of 20 ms. The amplitude of the motor evoked potential (MEP) was recorded. Results: In experiments targeting the left M1, both the healthy group (Experiment 1) and the patient group (Experiment 3) exhibited significant regulatory effects ( χ ² = 12.2, p = 0.002; χ ² = 9.6, p = 0.008). Post-hoc analysis revealed that, compared to baseline, both ipsilateral DLPFC ( p = 0.011; p = 0.022) and contralateral DLPFC ( p = 0.005; p = 0.022) significantly enhanced M1 excitability, with no significant difference between the two ( p = 1.000). However, in experiments targeting the right M1 across all groups (Experiments 2 and 4), no significant regulatory effect of DLPFC was observed ( χ ² = 0.2, p = 0.905). Conclusion: This study confirms that, at rest, the bilateral DLPFC exerts a stable and non-specific facilitatory regulation on the left M1. This effect persists in the affected M1 of stroke patients, suggesting plasticity in the relevant pathways after injury. The negative findings for the right M1 reveal a lateralization characteristic in DLPFC-M1 regulation. These results provide an important basis for elucidating the physiological mechanisms of cognitive-motor circuits and for developing targeted neurorehabilitation strategies.

Background: Effectively decoding electroencephalogram (EEG) pattern for specific mental tasks is a crucial topic in the development of brain-computer interface (BCI). Extracting common spatial pattern (CSP) features from motor imagery EEG signals is often highly dependent on the selection of frequency band and time interval. Therefore, optimizing frequency band and time interval would contribute to effective feature extraction and accurate EEG decoding.Objective: This study proposes an approach based on an improved novel global harmony search (INGHS) to optimize frequency-time parameters for effective CSP feature extraction.Methods: The INGHS algorithm is applied to find the optimal frequency band and temporal interval. The linear discriminant analysis and support vector machine are used for EEG pattern decoding. Extensive experimental studies are conducted on three EEG datasets to assess the effectiveness of our proposed method.Results: The average test accuracy obtained by the time-frequency parameters selected by the proposed INGHS method is slightly better than artificial bee colony (ABC) and particle swarm optimization (PSO) algorithms. Furthermore, the INGHS algorithm is superior to PSO and ABC in running time.Conclusion: These superior experimental results demonstrate that the optimal frequency band and time interval selected by the INGHS algorithm could significantly improve the decoding accuracy compared with the traditional CSP method. This method has a potential to improve the performance of MI-based BCI systems.