Background: Patients with neuropathic pain (NP), caused by injury or disease of the somatosensory nervous system, usually suffer from severe pain. Our previous studies revealed that electroacupuncture (EA) stimulation could effectively improve NP. However, the underlying mechanisms of EA have not been fully clarified. This study aimed to investigate the specific mechanisms of EA in alleviating NP, focusing on the pyroptosis. Materials and Methods: Chronic Constriction Injury (CCI) model was established on the male Sprague-Dawley rats. CCI rats were treated with EA at acupoints GV20 and ST36 or/with the NOD-like receptor protein 3 (NLRP3) antagonist MCC950. EA treatment was administered for successive 14 days 7 days after the CCI surgery. The mechanical withdrawal threshold (MWT) and paw withdrawal latency (PWL) were performed during the experiment. At the end of the experiment, spinal cord segments and serum of rats were collected, ELISA detected the expression of inflammatory factors, immunofluorescence detected the microglia and neuron cells with pyroptosis biomarkers, and Western blot detected the NLRP3 pathway. Results: EA treatment significantly alleviated pain hypersensitivity by increasing the MWT and PWL. Moreover, EA reduced levels of pro-inflammatory cytokines IL-1β and TNF-α in the spinal tissue. Mechanistically, the pyroptosis-related proteins, including NLRP3, N-GSDMD, Cleaved Caspase-1, IL-18 as well as IL-1β were downregulated by EA, indicating that EA attenuated the pyroptosis phenotype in NP rats. In particular, EA reduced the co-expression of NLRP3, Caspase-1 and N-GSDMD in microglia rather than in neuronal or astrocytic cells within the spinal cord of CCI rats. Pharmacological inhibition of NLRP3 inflammasome by MCC950 alleviates CCI-induced pain hypersensitivity while blocking EA’s effect on anti-pyroptosis in CCI rats. Conclusion: These findings demonstrate the EA ameliorates the neuroinflammation and pyroptosis to relieve chronic NP by suppressing NLRP3 inflammasome activation in microglia. EA may serve as a viable treatment therapy for chronic NP.

Study Design.: A retrospective, cross-sectional cohort study. Objective.: This study aimed to investigate the association between paraspinal muscle parameters and single-segment degenerative lumbar spondylolisthesis (DLS). Summary of Background Data.: The relationship between lumbar paraspinal muscle morphology and single-segment DLS remains unclear. Methods.: A retrospective review was conducted on 115 patients with L4/5 single-segment DLS and 105 subjects without DLS. Two independent investigators assessed the relative cross-sectional area and fat infiltration rate of the multifidus, erector spinae, and psoas major at L3/4, L4/5, and L5/S1 levels, comparing these measurements between the 2 groups. In addition, binary logistic regression analysis was performed with DLS as the dependent variable to analyze the relative cross-sectional area and fat infiltration rate of different paraspinal muscles. Within the DLS group, the correlation between paraspinal muscle characteristics and the anteroposterior diameter of the spinal canal was examined. Results.: The fat infiltration rate of multifidus, erector spinae, and psoas major was higher in the DLS group than in the control group, whereas the relative cross-sectional area of multifidus and psoas major was lower in the DLS group. Binary logistic regression analysis revealed a significant correlation between the fat infiltration rate of multifidus and psoas major and DLS. The relative cross-sectional area of multifidus and erector spinae was significantly smaller below the affected segment in the DLS group compared with the control group. A significant positive correlation was observed between the relative cross-sectional area of multifidus and erector spinae and the anteroposterior diameter of the spinal canal. Conclusion.: There is a close association between paraspinal muscle degeneration and single-segment DLS, with an increased relative cross-sectional area of the multifidus and psoas major possibly being risk factors for single-segment DLS. The restoration or enhancement of paraspinal muscle function could potentially serve as a pivotal target for the prevention and treatment of single-segment DLS. Level of Evidence.: Level III.

To critically evaluate the effects of manual therapy (MT) on pain and functional improvement in patients with rotator cuff injury (RCI), a systematic review of all randomized controlled trials (RCTs) on MT for RCI was conducted in the following databases: PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science, Physiotherapy Evidence Database, Chinese National Knowledge Infrastructure, Wan‑fang Data, Chinese Scientific Journal Database, and Chinese Biomedical Literature database from inception to March 28, 2023. A total of 1,110 participants from 24 eligible RCTs were included in the analysis. Compared with placebo, MT could not effectively relieve pain [standardized mean difference (SMD)=‑0.25; 95% CI: ‑0.51 to 0.01; P=0.06], although its impact on functional improvement appears limited (SMD=0.20; 95% CI: ‑0.09 to 0.49; P=0.18). Combining MT with exercise had significant advantages over exercise alone, as combined therapy contributed to both pain reduction (SMD=0.36; 95% CI: 0.08 to 0.64; P=0.01) and functional enhancement (SMD=0.32; 95% CI: 0.11 to 0.52; P=0.002). Furthermore, MT combined with multimodal physiotherapy showed additional benefits in pain reduction (mean difference=1.57; 95% CI: 0.18 to 2.96; P=0.03) and functional improvement (SMD=0.77; 95% CI: 0.43 to 1.12; P<0.0001) compared with multimodal physiotherapy alone. These findings highlight the superior pain alleviation and functional improvement provided by MT when combined with exercise or physiotherapy. Consequently, MT has emerged as a pivotal component of therapeutic intervention for RCI.

Background: Anxiety disorders are the most prevalent class of lifetime disorders in China, and generalized anxiety disorder (GAD) is one of the most common but frequently overlooked anxiety disorders. Conventional pharmacological treatments for GAD have varying degrees of side effects, dependency, and/or withdrawal syndromes. Traditional Chinese medicine (TCM) is considered a valuable therapeutic option for anxiety disorders and a potentially effective technique to reduce the side effects associated with antipsychotic drugs. This trial aimed to evaluate the clinical efficacy and safety of Antianxiety Granule, a granular Chinese medicine compound, for treatment of GAD. Methods/design: The current work is a multicentre, randomized, double-blind, placebo-controlled, parallel-group clinical trial with a 6-week treatment schedule. The study consists of three periods: a 1–7-day screening period, a 6-week primary treatment period, and a 1-week follow-up period. Follow-up assessments will be conducted 1 week after the last visit with a face-to-face interview or by telephone. The clinical efficacy of Antianxiety Granule for the treatment of GAD will be evaluated by examining the change in the Hamilton anxiety scale (HAMA) score, state-trait anxiety inventory (STAI) score, and TCM symptom scale in patients with GAD who receive daily TCM treatment. Moreover, an intention-to-treat (ITT) analysis will also be used in this randomized controlled trial (RCT). Discussion: Our study is a multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the safety and efficacy of Antianxiety Granule for the treatment of GAD. The results of this trial will provide valuable clinical evidence for the treatment of GAD. Trial registration: Chinese Clinical Trial Registry, ChiCTR1800016039. Registered on 8 May 2018.

Background: Rotator cuff-related shoulder pain (RCRSP) is the most common cause of shoulder disorders. In China, manipulation has been used extensively for the treatment of patients with RCRSP. However, high-quality clinical evidence to support the therapeutic effect of manipulation is still limited. Methods: A multicenter, participant-, outcome assessor-, and data analyst-blinded, randomized, placebo-controlled trial will be conducted. A total of 280 participants with RCRSP will be recruited from three hospitals and randomly assigned to a five-step shoulder manipulation (FSM) group or a sham manipulation (SM) group. Each group will receive four weekly treatment sessions, with all participants performing exercises at home for 12 weeks. Assessments, namely the Constant–Murley score, visual analog scale, range of motion, and 36-Item Short Form Survey, will be made at baseline, 4, 12, 18, and 24 weeks. Adverse events during the study will also be recorded. Discussion: This is a pragmatic clinical trial to evaluate the efficacy and safety of FSM in patients with RCRSP. The findings of this study will provide worthy clinical evidence for manual therapy for RCRSP. Trial registration: China Registered Clinical Trial Registration Center ChiCTR2000037577. Registered on 29 August 2020.

Background: Osteoarthritis (OA) is a common degenerative joint disorder and there are currently no effective therapies to impede its destructive progression. Astragaloside IV (AS-IV), a natural compound, exhibits promising chondroprotective effects, yet its specific molecular mechanisms remain poorly clarified. Thus, this study employed transcriptomic profiling combined with bioinformatics analysis to identify OA-related characteristic genes, and further conducted experiments to verify the potential therapeutic mechanism of AS-IV. Methods: Analysis of the GSE114007 dataset was performed using False Discovery Rate (FDR)-adjusted p-values and quantile normalization to mitigate batch effects. Weighted gene co-expression network analysis (WGCNA) was utilized to identify key modules. Nine OA-related feature genes were identified and validated in two external datasets (GSE129147 and GSE51588) using LASSO with 10-fold cross-validation and a random forest algorithm to minimize the risk of optimistic bias. Furthermore, gene set enrichment analysis (GSEA) was conducted. The underlying mechanisms were validated through molecular docking, cellular thermal shift assay (CETSA), as well as in vitro experiments using ATDC-5 cells and in vivo assays with OA mice. Results: We identified 1548 differentially expressed genes (DEGs) primarily enriched in the extracellular matrix, with PI3K-Akt signaling closely related to OA. The MEBlack module was strongly associated with OA (cor = −0.79, p<0.0001). GSEA showed the feature genes were associated with the adipocytokine signaling pathway and glycosaminoglycan biosynthesis. Furthermore, molecular docking and CETSA indicated that ETS2 served as a potential interacting target of AS-IV. In the destabilization of the medial meniscus (DMM)-induced OA mice, the results of Safranin O/Fast Green staining confirmed that AS-IV alleviated cartilage loss and lowered OARSI scores. Mechanistically, AS-IV slowed OA progression by upregulating Col2a1 expression, suppressing MMP13 levels, and reducing inflammatory markers such as IL-1β and TNF-α. Importantly, AS-IV enhanced ETS2 expression in osteoarthritic chondrocytes. Consistently, in vitro functional assays revealed that knockdown of ETS2 in chondrogenic ATDC-5 cells partially reversed both the chondroprotective and anti-inflammatory effects of AS-IV, verifying the essential role of ETS2 in mediating the therapeutic effects of AS-IV against OA. Conclusion: Collectively, these findings point to the vital function of ETS2 in OA pathogenesis and demonstrate that AS-IV attenuates cartilage degradation and inflammatory responses by upregulating ETS2, thereby retarding OA development.