Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, cartilage degradation, and bone erosion. The diseases also involves pathological changes in the surrounding fascial tissues that lead to persistent pain. Current clinical treatments rely primarily on non-steroidal anti-inflammatory drugs and analgesics, which often have limited efficacy and potential side effects. Manual acupuncture (MA), a traditional therapeutic modality, has shown promising effects in alleviating RA-related symptoms. However, the underlying mechanisms remain largely unclear. Fibroblasts, which are known for their mechanosensitivity and immunomodulatory functions, may play a crucial role in mediating the therapeutic effects of acupuncture. In this study, we demonstrated that MA significantly ameliorated pathological changes in joint-associated fascia in a murine model of adjuvant-induced arthritis with minimal impact on bone and cartilage morphology. Post-acupuncture analysis revealed the upregulation of extracellular matrix (ECM)-related genes and proteins, such as fibromodulin, collagen I, and hyaluronan synthase 2, along with increased expression of mechanosensitive molecules, including Piezo1, Ras homolog family member A (RhoA), and Yes-associated protein 1 (YAP1). Moreover, local changes were observed in the expression of fibroblast-associated markers including Fibroblast Growth Factor 2 (FGF-2), Fibroblast Growth Factor 7 (FGF-7), Fibroblast-Specific Protein 1 (FSP-1), Cannabinoid Receptor 2 (CB2), and Proliferating Cell Nuclear Antigen (PCNA). Notably, selective ablation of fibroblasts in the acupoint area via recombinant adeno-associated virus -mediated apoptosis significantly attenuated the analgesic effect of acupuncture, accompanied by reduced collagen fiber deposition, decreased mast cell degranulation, and downregulation of ECM components and regulatory molecules, such as Hyaluronan Binding Protein 2 (HABP2) and CB2. In conclusion, the study findings suggest that acupuncture alleviates RA-induced pathological and pain responses by activating fibroblasts in the fascial tissue. This mechanotransduction process likely involves the downstream modulation of cannabinoid receptors and ECM-related proteins, including hyaluronic acid and collagen.

The neuro-endocrine-immune (NEI) network is a key regulatory network that maintains organismal homeostasis and participates in stress responses. Its function depends on the dynamic coupling among the nervous, endocrine, and immune systems. Astrocytes, as abundant and functionally diverse glial cells in the central nervous system, are increasingly recognized as important participants in the NEI network. Growing evidence indicates that astrocytes do not merely provide structural support in the traditional sense, but also exhibit marked regional heterogeneity and functional diversity. Through broad sensing of neural, endocrine, and immune signals, gliotransmitter release, metabolic regulation, extracellular vesicle-mediated communication, and interactions with neurons, glial cells, the glymphatic system, and endocrine axes, astrocytes actively participate in the integration of neural activity, the regulation of endocrine homeostasis, and immune responses. Under physiological conditions, astrocytes contribute to the dynamic balance of the NEI network by integrating multisource signals derived from neurons, endocrine factors, and immune molecules. Under pathological conditions, such as inflammation, ischemia, and neurodegenerative diseases, the phenotype and function of astrocytes undergo substantial remodeling, thereby contributing to NEI network dysregulation and disease progression. In this structured narrative review, literature published between 2016 and 2026 was retrieved from the PubMed and Web of Science databases using “astrocytes,” “nervous,” “endocrine,” and “immune” as search terms. It summarizes the structural and functional basis of astrocytes and the mechanisms by which they regulate the NEI network, with the aim of systematically elucidating the physiological and pathological significance of astrocytes in NEI network integration and providing a theoretical basis for mechanistic studies and targeted intervention strategies for related diseases.

The study of patient‒clinician relationships is a vital branch of interpersonal interaction research. Acupuncture attaches great importance to positive patient‒clinician interactions; thus, it serves as a typical example of patient‒clinician interaction research. Based on electroencephalography (EEG) hyperscanning, this study explored inter-brain similarity based on spatial correlations between two brains as well as inter-brain connectivity of different regions through different frequency bands. Regarding inter-brain similarity, both acupuncture and sham acupuncture significantly decreased spatial correlation during certain sessions during acupuncture. Regarding inter-brain connectivity, acupuncture enhanced not only the connectivity of the beta frequency band in the right temporoparietal regions but also the connectivity of the fast-ripple frequency band in the right and left temporoparietal regions. These results suggest that inter-brain similarity should be emphasized in patient–clinician relationship research. Moreover, high-frequency oscillations (HFOs) potentially play an important role in inter-brain connectivity in addition to the classical EEG low-frequency bands. ### Competing Interest Statement The authors have declared no competing interest. Scientific and Technological Innovation Project of the China Academy of Chinese Medical Sciences, , Fundamental Research Funds for the Central Public Welfare Research Institutes, ,

At present, a number of studies have shown that acupuncture at Zusanli (ST 36) can relieve pain, but the changes of local microenvironment in the acupoint area after acupuncture have not been elucidated. As a temperature and pain receptor, TRPV1 plays an important role in pain perception and inflammation regulation. In this study, RT-PCR technique was used to screen the types of mechanically sensitive ion channels in the local response to acupuncture in the acupoint area, and western bolt technique was used to verify in gene knockout and antagonist injection mice. Immunofluorescence double labeling technique was used to further determine the key cell types of TRPV1-mediated acupuncture analgesia. Finally, through the combined analysis of proteomics and phosphorylated proteomics, the local signaling pathways of acupoints that can be activated by acupuncture were analyzed. This study systematically explored the analgesic effect of acupuncture on inflammatory pain in mice and its mechanism. The study found that acupuncture can significantly improve the thermal pain threshold and mechanical pain threshold in mice, showing a significant analgesic effect. Further analysis revealed that this analgesic effect was closely related to the up-regulation of local TRPV1 expression at ST36, and its deletion or functional inhibition would significantly weaken the analgesic effect of acupuncture. In addition, we also found that acupuncture in the deep muscle layer can more effectively promote the expression and activity of TRPV1 than in the superficial fascia layer, and muscle cells are the key cell types of TRPV1-mediated acupuncture analgesia. Finally, through the combined analysis of multi-omics, it was clear that acupuncture could activate the local signal pathway TRPV1/CaMKII/AMPK/PGC1α to exert analgesic effect. In conclusion, this study not only confirmed the analgesic effect of acupuncture on inflammatory pain in mice, but also revealed the core role of TRPV1 in the mechanism of acupuncture analgesia, especially the important contribution of TRPV1 expression and activity in the muscle layer of ST36 acupoint to the analgesic effect of acupuncture, which provided a new scientific basis and potential therapeutic target for acupuncture treatment of inflammatory pain.

Clinical studies have revealed a significant correlation between pain and neurodegenerative diseases, particularly Alzheimer's disease (AD). However, due to cognitive and speech impairments, AD patients, especially those in moderate to severe stages, are often overlooked in pain management. The challenges in obtaining pain-related information from this population exacerbate the issue. Although recent clinical research has increasingly recognized the comorbidity of AD and pain, the pathological alterations and interactive mechanisms underlying this relationship remain inadequately explored. This review provides a comprehensive analysis of the clinical features and pathological mechanisms of AD with and without pain comorbidity. It examines underlying processes, including neuroinflammation, peripheral-central immune interactions, and neurotransmitter dynamics. Furthermore, it highlights current pain assessment and management strategies in AD patients. By offering a theoretical framework, this review aims to support the development of effective pain management approaches and serve as a reference for clinical interventions targeting AD-associated pain. HIGHLIGHTS: The comorbidity between AD and CP encompasses multiple interrelated biological pathways, such as neurodegeneration and inflammatory responses. The damage to neurons and synapses in AD patients influences the brain regions responsible for processing pain, thereby reducing the pain response. Neuroinflammation plays a vital role in the development of both AD and CP. Enhanced inflammatory responses have an impact on the CNS and promote sensitization. Common neurotransmitter alterations exist in the comorbidity of AD and CP, influencing cognition, emotion, and pain perception.

Neuroinflammation and immune system dysregulation are critical contributors to the pathogenesis of Parkinson’s disease (PD). Although emerging inflammatory biomarkers, such as the hemoglobin-to-red blood cell distribution width ratio (HRR) and systemic inflammation response index (SIRI), may be significantly relevant, their relationship with PD has not been thoroughly explored. This study aimed to investigate the association between HRR and PD risk in middle-aged and older adults and evaluate the potential mediating role of SIRI in this association. A cross-sectional study was performed using data from 24,019 participants in the National Health and Nutrition Examination Survey (NHANES) 2005–2018. To investigate the relationship between HRR and PD prevalence, multivariable logistic regression models, restricted cubic spline (RCS) analyses, and subgroup analyses were employed. Additionally, a mediational analysis was performed to evaluate the potential mediating effect of the SIRI on this association. In a cohort of 24,019 participants, 347 individuals (1.4%) were diagnosed with PD. Multivariable-adjusted logistic regression demonstrated that each one-unit increase in HRR was associated with an 88% reduction in the odds of PD (odds ratio [OR] = 0.12, 95% confidence interval: 0.05-0.30). Conversely, each one-unit increase in the SIRI corresponded to a 15% increase in the odds of PD (OR = 1.15, 95% confidence interval: 1.03-1.28). RCS analysis revealed a crucial inverse linear association between HRR and PD. Subgroup analyses confirmed the robustness of the inverse association between HRR and PD. Additionally, analysis of the mediational effects revealed that the SIRI mediated 4.85% of the association between HRR and PD (p < 0.05). These findings demonstrate a crucial inverse correlation between reduced HRR and higher PD prevalence, with SIRI acting as a partial mediator. The results revealed a potential correlation among HRR, SIRI, and PD, suggesting that monitoring and managing HRR and SIRI levels may constitute a potential approach for mitigating PD prevalence.

Mechanical forces are crucial in regulating fibroblast behavior, yet the underlying mechanisms remain unclear. This study aims to elucidate the role of the Piezo1 ion channel in fibroblast responses to mechanical stimulation. A mechanical stimulation culture platform was developed using a polydimethylsiloxane (PDMS)-based stretchable membrane and the Cell Tank uniaxial cell stretching system. Fibroblasts subjected to uniaxial cyclic stretching were analyzed using proteomic profiling, Western blotting, and confocal laser scanning microscopy to assess cytoskeletal changes and activation markers. Immunofluorescence staining was performed to evaluate the expression of Piezo1, YAP1, and Ki67 proteins. Cell viability and migration capacity were assessed using Calcein-AM/PI double staining and a migration assay. Mechanical stretch-induced fibroblast activation is characterized by morphological changes, increased proliferation, and enhanced migration. The cytoskeletal reorganization was observed, with elevated F-actin expression. Modulating Piezo1 activity altered fibroblast activation, indicating its essential role in mechanotransduction. These findings demonstrate that mechanical stretch upregulates Piezo1 expression, promoting fibroblast activation through the YAP pathway. This study provides new insights into the mechanotransduction mechanisms in fibroblasts and highlights the critical role of Piezo1 in mediating responses to mechanical stimuli, which may have implications for understanding tissue remodeling and fibrosis.

Depression, a highly prevalent mental disorder worldwide, arises from multifaceted interactions involving neurotransmitter imbalances, inflammatory responses, and gut–brain axis dysregulation. Emerging evidence highlights the pivotal role of bile acids (BAs) and their receptors, including farnesoid X receptor (FXR), Takeda G protein-coupled receptor 5 (TGR5), and liver X receptors (LXRs) in depression pathogenesis through modulation of neuroinflammation, gut microbiota homeostasis, and neural plasticity. Clinical investigations demonstrated altered BA profiles in depressed patients, characterized by decreased primary BAs (e.g., chenodeoxycholic acid (CDCA)) and elevated secondary BAs (e.g., lithocholic acid (LCA)), correlating with symptom severity. Preclinical studies revealed that BAs ameliorate depressive-like behaviors via dual mechanisms: direct CNS receptor activation and indirect gut–brain signaling, regulating neuroinflammation, oxidative stress, and BDNF/CREB pathways. However, clinical translation faces challenges including species-specific BA metabolism, receptor signaling complexity, and pharmacological barriers (e.g., limited blood–brain barrier permeability). While FXR/TGR5 agonists exhibit neuroprotective and anti-inflammatory potential, their adverse effects (pruritus, dyslipidemia) require thorough safety evaluation. Future research should integrate multiomics approaches and interdisciplinary strategies to develop personalized BA-targeted therapies, advancing novel treatment paradigms for depression.

Purpose:Acupuncture (ACU) has been demonstrated to alleviate inflammatory pain. Mechanoreceptors are present in acupuncture points. When acupuncture exerts mechanical force, these ion channels open and convert the mechanical signals into biochemical signals. TRPA1 (T ransient receptor potential ankyrin 1) is capable of sensing various physical and chemical stimuli and serves as a sensor for inflammation and pain. This protein is expressed in immune cells and contributes to local defense mechanisms during early tissue damage and inflammation. In this study, we investigated the role of TRPA1 in acupuncture analgesia.Patients and Methods:We injected complete Freund's adjuvant (CFA) into the mouse plantars to establish a hyperalgesia model. Immunohistochemistry and immunofluorescence analyses were performed to determine the effect of acupuncture on the TRPA1 expression in the Zusanli (ST36). We used TRPA1-/- mouse and pharmacological methods to antagonize TRPA1 to observe the effect on acupuncture analgesia. On this basis, collagenase was used to destroy collagen fibers at ST36 to observe the effect on TRPA1.Results:We found that the ACU group vs the CFA group, the number of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 increased significantly. In CFA- inflammatory pain models, the TRPA1-/- ACU vs TRPA1+/+ ACU groups, the paw withdrawal latency (PWL) and paw withdrawal threshold (PWT) downregulated significantly. In the ACU + high-, ACU + medium-, ACU + low-dose HC-030031 vs ACU groups, the PWL and PWT were downregulated, and in carrageenan-induced inflammatory pain models were consistent with these results. We further found the ACU + collagenase vs ACU groups, the numbers of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 were downregulated.Conclusion:These findings together imply that TRPA1 plays a significant role in the analgesic effects produced via acupuncture at the ST36. This provides new evidence for acupuncture treatment of painful diseases.

Depression is a common mental disorder caused by the interaction of social, psychological, and biological factors. Treatments include psychotherapy, pharmacotherapy, and other therapies, but they have limitations. Particularly, the COVID-19 pandemic may have a negative impact on depressed people. Thus, developing more potential treatments for depression has currently been an urgent challenge. A growing number of studies have found that acupressure is effective in relieving the symptoms of depression. Thus, this study aimed to evaluate the efficacy and safety of acupressure in people with depression. English (PubMed, CENTRAL, EMBASE, APA PsycINFO, and CINAHL) and Chinese databases (CBM, CNKI, Wanfang, and VIP), ClinicalTrials.gov and Chinese Clinical Trial Registry were searched for randomized controlled trials (RCTs) on patients diagnosed with depression from study inception until March 31, 2023. Studies that compared acupressure with sham acupressure, conventional treatments (i.e., medication, usual care, etc.), and acupressure as an adjunct to conventional treatment for depression were included. The primary outcome was depression level measured using the Hamilton Depression Scale, Self-Rating Depression Scale, or Geriatric Depression Scale. A total of 19 RCTs involving 1686 participants were included. The pooled results showed that acupressure exhibited a significant beneficial effect on reducing the severity of depression compared with sham acupressure and served as an adjunct to conventional treatment, although the evidence level was moderate. Thus, acupressure may be a potential treatment for depression.

In the past few decades, the use of acupuncture analgesia in clinical practice has increased worldwide. This is due to its various benefits, including natural alleviation of pain without causing various adverse effects associated with non-steroidal anti-inflammatory drugs (NSAID) and opioids. The acupoint represents the initial site of acupuncture stimulation, where diverse types of nerve fibers located at the acupoint hold significant roles in the generation and transmission of acupuncture-related information. In this study, we analyzed the patterns and mechanisms of acupuncture analgesic mediated by acupoint afferent fibers, and found that acupuncture stimulates acupoints which rapidly and directly induces activation of high-density primary afferent fibers under the acupoints, including myelinated A fibers and unmyelinated C fibers. During acupuncture stimulation at the muscle layer, the analgesic effects can be induced by stimulation of A fiber threshold intensity. At the skin layer, the analgesic effects can only be produced by stimulation of C fiber threshold intensity. Electroacupuncture (EA) activates A fibers, while manual acupuncture (MA) activates both A and C fibers. Furthermore, acupuncture alters acupoint microenvironments, which positively modulates afferent fibers, enhancing the transmission of analgesic signals. In addition to local activation and conduction at acupoints, nerve fibers mediate the transmission of acupuncture information to pain centers. In the spinal cord, acupuncture activates neurons by inducing afferent fiber depolarization, modulating pain gating, inhibiting long-term potentiation (LTP) of the spinal dorsal horn and wide dynamic range (WDR) neuronal activities. At higher nerve centers, acupuncture inhibits neuronal activation in pain-related brain regions. In summary, acupuncture inhibits pain signal transmission at peripheral and central systems by activating different patterns of afferent fibers located on various layers of acupoints. This study provides ideas for enhancing the precise application and clinical translation of acupuncture.

Objective To observe whether acupuncture up-regulates chemokine CXC ligand 1(CXCL1)in the brain to play an analgesic role through CXCL1/chemokine CXC receptor 2(CXCR2)signaling in adjuvant induced arthritis(AIA)rats,so as to reveal its neuro-immunological mechanism underlying improvement of AIA.Methods BALB/c mice with relatively stable thermal pain reaction were subjected to planta injection of complete Freund adjuvant(CFA)for establishing AIA model,followed by dividing the AIA mice into simple AF750(fluorochrome)and AF750+CXCL1 groups(n=2 in each group).AF750 labeled CXCL1 recombinant protein was then injected into the mouse's tail vein to induce elevation of CXCL1 level in blood for simulating the effect of acupuncture stimulation which has been demonstrated by our past study.In vivo small animal imaging technology was used to observe the AF750 and AF750+CXCL1-labelled target regions.After thermal pain screening,the Wistar rats with stable pain reaction were subjected to AIA modeling by injecting CFA into the rat's right planta,then were randomized into model and manual acupuncture groups(n=12 in each group).Other 12 rats that received planta injection of saline were used as the control group.Manual acupuncture(uniform reinforcing and reducing manipulations)was applied to bilateral"Zusanli"(ST36)for 4×2 min,with an interval of 5 min between every 2 min,once daily for 7 days.The thermal pain threshold was assessed by detecting the paw withdrawal latency(PWL)using a thermal pain detector.The contents of CXCL1 in the primary somatosensory cortex(S1),medial prefrontal cortex,nucleus accumbens,amygdala,periaqueductal gray and rostroventromedial medulla regions were assayed by using ELISA,and the expression levels of CXCL1,CXCR2 and mu-opioid receptor(MOR)mRNA in the S1 region were detected using real time-quantitative polymerase chain reaction.The immune-fluorescence positive cellular rate of CXCL1 and CXCR2 in S1 region was observed after immunofluorescence stain.The immunofluorescence double-stain of CXCR2 and astrocyte marker glial fibrillary acidic protein(GFAP)or neuron marker NeuN or MOR was used to determine whether there is a co-expression between them.Results In AIA mice,results of in vivo experiments showed no obvious enrichment signal of AF750 or AF750+ CXCL1 in any organ of the body,while in vitro experiments showed that there was a stronger fluorescence signal of CXCL1 recombinant protein in the brain.In rats,compared with the control group,the PWL from day 0 to day 7 was significantly decreased(P<0.01)and the expression of CXCR2 mRNA in the S1 region significantly increased in the model group(P<0.05),while in comparison with the model group,the PWL from day 2 to day 7,CXCL1 content,CXCR2 mRNA expression and CXCR2 content,and MOR mRNA expression in the S1 region were significantly increased in the manual acupuncture group(P<0.05,P<0.01).Immunofluorescence stain showed that CXCR2 co-stained with NeuN and MOR in the S1 region,indicating that CXCR2 exists in neurons and MOR-positive neurons but not in GFAP positive astrocytes.Conclusion Acupuncture can increase the content of CXCL1 in S1 region,up-regulate CXCR2 on neurons in the S1 region and improve MOR expression in S1 region of AIA rats,which may contribute to its effect in alleviating inflammatory pain.

Abstract Introduction: Depression seriously affects the health of people all over the world. At the early stage of depression, subthreshold depression is very important for early prevention and treatment of depression. The hand twelve Jing -well points exercise is traditional Chinese therapy for acupoint stimulation. We designed a parallel randomized clinical trial to observe the intervention effect of hand twelve Jing -well points exercise on subthreshold depression in college students. Methods: This is a randomized, parallel controlled clinical trial. Sixty-two eligible participants will be randomly assigned to the intervention group or the waiting-list control group according to the ratio of 1: 1. The intervention group will be received hand twelve Jing -well points exercise for 16 weeks. The waiting-list control group will not receive the intervention and participants will be taught the hand twelve Jing -well points exercise after the experiment. The main outcomes are Self-rating Depression Scale and Beck Depression Inventory-II, and the secondary outcomes are Pittsburgh Sleep Quality Index, reward processing cognitive behavioral data and functional Near-Infrared Spectroscopy data, which will be detected at baseline, 4 weeks and 16 weeks after the intervention. Discussion: A randomized controlled trial will be conducted to assess the effectiveness of hand twelve Jing -well points exercise on patients with subthreshold depression so as to provide evidence for further promoting subthreshold depression management. Trial registration: Chinese Clinical Trial Registry, Registration number :ChiCTR2100052960;Registered on November 6th, 2021.

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Subthreshold depression refers to the presence of depressive symptoms but does not meet the clinical diagnostic criteria of depression. As a risk index of depression, the prevention of depression should start from Subthreshold depression. This review summarizes the existing cognitive and brain mechanisms of subthreshold depression, and finds that subthreshold depression has abnormalities in the frontal lobe, parietal lobe, hippocampus, amygdala, cingulate gyrus, fusiform gyrus, striatum, insula and other brain regions compared with normal people, and with the increase of the degree of depression, there will be a higher degree of cognitive impairment. In the future, we can focus on the identification of subthreshold depression and targeted intervention to prevent the occurrence of depression.

Recently, increasing numbers of studies have demonstrated that transient receptor potential ankyrin 1 (TRPA1) can be used as a potential target for the treatment of inflammatory diseases. TRPA1 is expressed in both neuronal and non-neuronal cells and is involved in diverse physiological activities, such as stabilizing of cell membrane potential, maintaining cellular humoral balance, and regulating intercellular signal transduction. TRPA1 is a multi-modal cell membrane receptor that can sense different stimuli, and generate action potential signals after activation via osmotic pressure, temperature, and inflammatory factors. In this study, we introduced the latest research progress on TRPA1 in inflammatory diseases from three different aspects. First, the inflammatory factors released after inflammation interacts with TRPA1 to promote inflammatory response; second, TRPA1 regulates the function of immune cells such as macrophages and T cells, In addition, it has anti-inflammatory and antioxidant effects in some inflammatory diseases. Third, we have summarized the application of antagonists and agonists targeting TRPA1 in the treatment of some inflammatory diseases.

Abstract Alzheimer's disease (AD), which mainly manifested by cognitive decline, affects millions of elderly people around the world. With the global aging continues to accelerate, the incidence of AD is also increasing year by year. The chronic, persistent, and irreversible decline of learning and memory ability of AD brings serious harm and economic burden to families and society. Because of its complex of pathogenesis, there is still a lack of effective treatment for AD. Acupuncture, as one of the complementary and alternative therapies, has provided a promising avenue for the treatment of AD. This study comprehensively reviews literature from the last ten years, showing that acupuncture indeed exerts strong beneficial effects on AD. Acupuncture can regulate the species and structure of the intestinal flora, repair the intestinal barrier and the brain blood barrier, prevent inflammatory cytokines and harmful substances in the intestine from entering the blood and brain to improve the cognitive impairment of AD. In addition to this, acupuncture can treat AD by regulating Aβ deposition (including inhibiting Aβ production and promoting Aβ clearance), inhibiting tau protein phosphorylation, improving the structure and function of neurons and synapses, promoting nerve regeneration, relieving chronic neuroinflammation, regulating energy metabolism and cerebral blood flow of the brain, etc. It is worth noting that the effect of acupuncture on AD is related to the selections of acupoints, the form and frequency of acupuncture, etc. Some special acupuncture methods, such as Sanjiao acupuncture and "olfactory three-needle" therapy, also provide new perspectives for AD. The therapeutic effect and potential mechanism of acupuncture on AD summarized in this study provide scientific and reliable evidence for acupuncture application for AD.

Rheumatoid arthritis (RA) is an autoimmune disease that generally affects the joints. In the face of inflammation-induced cartilage and bone damage, RA treatment remains insufficient. While research evidence indicates that acupuncture can exert anti-inflammatory and analgesic effects, improve the joint function of RA patients, and delay the disease, data on whether it can promote RA repair are lacking. Findings from the present work demonstrated that both the antigen-induced arthritis (AIA) and collagen-induced arthritis (CIA) models can simulate joint swelling of RA. The AIA model was more stable than the CIA model, with a higher incidence of successful arthritis modeling. Moreover, the AIA mice model could simulate the signal molecules and related pathological processes of the autoimmune response in RA, as well as major pathways related to RA and antigen immune response mechanisms. Manual acupuncture (MA) at Zusanli (ST36) significantly improved paw redness and swelling, pain, and inflammatory cell infiltration in the joints in AIA mice. The therapeutic effect of MA on AIA is achieved primarily through the regulation of steroid hormone biosynthesis, cell metabolism, and tissue repair processes. MA at ST36 can increase the gene contents of tissue repair growth factors, including PEG3 , GADD45A , GDF5 , FGF5 , SOX2 , and ATP6V1C2 in the inflammatory side joints of AIA mice, as well as the gene expression of the anti-inflammatory cytokine IL-10 . In conclusion, acupuncture may alleviate RA in the joints via modulating the tissue healing process.