Objective To evaluate the effectiveness of Tuina in relieving the pain, negative emotions, and disability of patients with knee osteoarthritis (KOA). Design Single-centre, parallel, randomized controlled trial. Setting Shanghai Guanghua Integrated Chinese and Western Medicine Hospital, Shanghai, China. Subjects Adult patients with KOA who were able to speak Chinese and self-report symptoms were eligible. Methods A total of 104 patients were randomly allocated to receive the 6-week treatment of Tuina (Tuina group) or celecoxib (celecoxib group). Data on pain, negative emotions, and disability were collected at baseline, at week 2, 4 and 6, and follow-up (one month after the last treatment). The primary outcomes were the pressure pain thresholds. The secondary outcomes were: (1) numerical rating scale at rest and with movement; (2) Hamilton Anxiety Scale; (3) Hamilton Depression Scale; (4) Western Ontario and McMaster Universities Osteoarthritis Index; and (5) clinical effective rate. The adverse events of the trial were evaluated. Results In total, 99 patients completed the follow-up. Generalized linear mixed models were constructed to analyse the between-group differences. Statistically significant differences were found in the interaction effects (p < 0.05). In evaluating the group effect, statistical differences were found at week 6 and follow-up (p < 0.05). Further, all variables showed a time effect (p < 0.05). A statistical difference in the clinical effective rate was found between the Tuina and celecoxib groups (p < 0.05). Conclusions Tuina produced superior effects for pain, negative emotions, and disability over time, as compared to celecoxib in patients with KOA.

Introduction: Knee osteoarthritis (KOA) is characterized by a degenerative change of knee cartilage and secondary bone hyperplasia, resulting in pain, stiffness, and abnormal walking gait. Long-term chronic pain causes considerable cortical plasticity alternations in patients. However, the brain structural and functional alterations associated with the pathological changes in knee joints of end-stage KOA patients remain unclear. This study aimed to analyze the structural and functional connectivity alterations in end-stage KOA to comprehensively understand the main brain-associated mechanisms underlying its development and progression. Methods: In this study, 37 patients with KOA and 37 demographically matched healthy controls (HCs) were enrolled. Alternations in gray matter (GM) volume in patients with KOA were determined using voxel-based morphometry. The region with the largest GM volume alteration was selected as the region of interest to calculate the voxel-wise resting-state functional connectivity (rs-FC) in the two groups. Pearson's correlation coefficient was used to analyze the correlation between clinical measures and GM volume alternations in patients with KOA. Results: Compared with HCs, patients with KOAs exhibited significantly decreased GM volumes in the left middle temporal gyrus (left-MTG) and the left inferior temporal gyrus. Results of the voxel-wise rs-FC analysis revealed that compared with HCs, patients with KOA had decreased left-MTG rs-FC to the right dorsolateral superior frontal gyrus, left middle frontal gyrus, and left medial superior frontal gyrus. GM volume in the left-MTG was negatively correlated with the Western Ontario and McMaster Universities Arthritis Index in patients with KOA (r = −0.393, p = .016). Conclusion: Structural remodeling and functional connectivity alterations may be one of the central brain mechanisms associated with end-stage KOA.

Introduction:We aimed to evaluate the efficacy of electroacupuncture in relieving acute pain after total knee arthroplasty (TKA) and related mechanism. Methods: In this randomized, single-blind, and sham-acupuncture controlled study. Forty patients with postoperative acute pain were recruited and randomly divided electroacupuncture group (n = 20) and sham-acupuncture group (n = 20) from November 2020 to October 2021. All patients received electroacupuncture or shamacupuncture for 5 days after TKA. Their brain regions were scanned with resting-state functional magnetic resonance imaging before and after intervention. Pain was scaled. Another 40 matched healthy controls underwent scanning once. The amplitude of low-frequency fluctuation (ALFF) values was compared. Pearson's correlation analysis was utilized to explore the correlation of ALFF with clinical variables in patients after intervention. Results: Compared with the HCs, patients with acute pain following TKA had significantly decreased ALFF value in right middle frontal gyrus, right supplementary motor area, bilateral precuneus, right calcarine fissure and surrounding cortex, and left triangular part of inferior frontal gyrus (false discovery rate corrected p < .05). Patients had higher ALFF value in bilateral precuneus, right cuneus, right angular gyrus, bilateral middle occipital gyrus, and left middle temporal gyrus after electroacupuncture Bingxin Kang, Chi Zhao, and Jie Ma contributed equally.

ObjectivesFibroblast‐like synoviocytes (FLS) contribute to inflammation and joint damage in rheumatoid arthritis (RA). However, the regulatory mechanisms of FLS in relapse and remission RA remain unknown. Identifying FLS heterogeneity and their underlying pathogenic roles may lead to discovering novel disease‐modifying antirheumatic drugs.MethodsCombining single‐cell RNA‐sequencing (scRNA‐seq) and spatial transcriptomics, we sequenced six matched synovial tissue samples from three relapse RA patients and three patients in remission. We analyzed the differences in the transcriptomes of the FLS subsets between the relapse and remitted phases. We validated several key signaling pathways using qPCR and multiplex immunohistochemistry (HC). We further targeted the critical signals in vitro and in vivo using collage‐induced arthritis (CIA) model in rats.ResultsLining and sublining FLS subsets were identified using scRNA‐seq. Differential analyses indicated that the fibroblast growth factor (FGF) pathway was highly activated in the lining FLS from relapse RA patients where mIHC confirmed the increased expression of FGF10. While the type I interferon pathway was also activated in the lining FLS, in vitro stimulation experiment suggested that it was independent of the FGF10 pathway. FGF10 knockdown by siRNA in FLS significantly reduced the expression of RANKL. Moreover, recombinant FGF10 protein enhanced bone erosion in the primary human‐derived pannus cell culture, whereas the FGFR1 inhibitor attenuated this process. Finally, administering an FGFR1 inhibitor displayed a therapeutic effect in a CIA rat model.ConclusionThe FGF pathway is a critical signaling pathway in relapse RA. Targeted tissue‐specific inhibition of FGF10/FGFR1 may provide new opportunities to treat patients with relapse RA.