Search Results (86)

Background/Objectives: Chronic non-specific low back pain is a leading cause of disability. Although therapeutic exercise and manual therapy are commonly recommended, their relative effects are often interpreted using broad therapeutic categories. This network meta-analysis aimed to compare the relative effectiveness of specific therapeutic exercise and manual therapy techniques on post-treatment self-reported disability in adults with chronic non-specific low back pain. Methods: A systematic review and frequentist random-effects network meta-analysis were conducted according to Cochrane recommendations and PRISMA-NMA guidance. The protocol was registered in PROSPERO (CRD42022331411). Randomized controlled trials including adults aged 18–65 years with chronic non-specific low back pain were searched in CENTRAL, PubMed, PEDro, Google Scholar, and SciELO up to 31 March 2026. Disability was assessed using the Roland–Morris Disability Questionnaire or Oswestry Disability Index. Effects were synthesized as standardized mean differences. Risk of bias was assessed with RoB 2, and confidence in network estimates was evaluated using CINeMA. Results: Forty-five studies were included. Compared with control/placebo, the largest favorable estimates were observed for equipment-based Pilates, stabilization with motor control, stabilization exercise, soft tissue manipulation, and Pilates Mat. Equipment-based Pilates showed the largest favorable estimate with moderate-confidence evidence, and soft tissue manipulation also showed moderate-confidence evidence. However, heterogeneity was substantial, and confidence in most favorable exercise estimates was low. Conclusions: Specific exercise and manual therapy techniques may reduce post-treatment disability in adults with chronic non-specific low back pain. Equipment-based Pilates and soft tissue manipulation showed favorable signals supported by moderate-confidence evidence. However, the findings do not support a definitive hierarchy of efficacy or categorical superiority of therapeutic exercise over manual therapy. Full article

Background/Objectives: Insomnia is one of the most prevalent and persistent symptoms among patients with breast cancer, yet it remains under-recognized and undertreated in routine clinical practice. Beyond its impact on sleep quality, insomnia is increasingly understood as a multidimensional condition involving neurobiological, psychological, and behavioral mechanisms, closely intertwined with cancer-related stress and psychiatric comorbidities. This narrative review aims to provide a comprehensive and integrative overview of insomnia in breast cancer, focusing on its epidemiology, pathophysiological underpinnings, neuropsychiatric correlates, and clinical implications, while highlighting gaps in current research and management. Methods: A narrative review of the literature was conducted, including studies published in major medical databases (PubMed, Scopus, and Web of Science) up to 2025. Relevant articles addressing insomnia, sleep disturbances, psychiatric symptoms, and neurobiological mechanisms in breast cancer populations were selected and synthesized. Results: Insomnia affects a substantial proportion of breast cancer patients across the disease trajectory, from diagnosis to survivorship. Its etiology is multifactorial, involving dysregulation of the hypothalamic–pituitary–adrenal axis, inflammatory processes, and circadian rhythm, as well as treatment-related factors such as chemotherapy, endocrine therapy, and menopausal symptoms. Insomnia frequently co-occurs with depression, anxiety, fatigue, and pain, forming symptom clusters that significantly impair quality of life and may influence clinical outcomes. Emerging evidence supports a bidirectional relationship between insomnia and psychiatric vulnerability, suggesting a shared neurobiological substrate within the brain–body stress axis. Conclusions: Insomnia in breast cancer should be conceptualized as a neuropsychiatric condition embedded within a broader stress-related symptom network rather than as an isolated sleep disturbance. Improved screening, interdisciplinary management, and the integration of evidence-based interventions such as cognitive behavioral therapy for insomnia are essential. Research should focus on personalized and mechanistically informed approaches to better address this highly prevalent yet insufficiently managed condition. Full article

Background: Multimodal rehabilitation represents standard practice in musculoskeletal care, where exercise therapy is routinely combined with manual therapy, electrotherapy, education, and cognitive–behavioral strategies. However, research has largely evaluated these modalities in isolation, and no bibliometric synthesis has characterized multimodal rehabilitation despite its predominance in routine practice. Objective: To characterize global research activity, thematic clusters, and diagnostic patterns underpinning multimodal musculoskeletal rehabilitation and to examine their alignment with contemporary rehabilitation guidelines and practice models. Methods: A bibliometric and altmetric analysis was performed using Web of Science Core Collection (1989–2026). Studies indexed under exercise therapy, manual therapy, electrotherapy, education, and cognitive–behavioral approaches were included. Network analyses (co-occurrence, co-authorship, thematic evolution, and bibliographic coupling) were conducted using Bibliometrix and VOSviewer. Diagnostic subgroups included osteoarthritis, low back pain, chronic musculoskeletal pain, tendinopathy, and shoulder disorders. Results: A total of 409 publications were identified. Five multimodal combinations were recurrent: exercise + education, exercise + cognitive–behavioral therapy, exercise + manual therapy, exercise + electrotherapy, and mixed multimodal programs. Diagnostic subgrouping showed distinct patterns, with osteoarthritis and low back pain clustering around exercise + education, chronic musculoskeletal pain around exercise + CBT/self-management, and tendinopathy/shoulder disorders around exercise + manual therapy. Temporal analyses demonstrated a shift from unimodal electrophysical agents toward guideline-aligned biopsychosocial models. Altmetric signals suggested relevant dissemination and policy attention. Conclusions: Multimodal musculoskeletal rehabilitation is research-intensive, diagnosis-specific, and aligned with guideline recommendations prioritizing exercise, education, self-management, and behavioral strategies. These findings support multimodal rehabilitation as a maturing evidence-based practice model with implications for pragmatic trials, guideline implementation, and clinical service delivery. Beyond research implications, these patterns are relevant for musculoskeletal care pathways, training of rehabilitation professionals and health system planning. Full article

Background: Migraine is a highly prevalent neurological disorder associated with substantial disability and socioeconomic burden. Although pharmacological therapies remain the mainstay of treatment, their effectiveness may be limited by incomplete response and adverse effects. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a non-invasive neuromodulatory technique that may modulate cortical excitability and pain-processing networks involved in migraine pathophysiology. This systematic review aimed to evaluate the current evidence regarding the efficacy and safety of rTMS compared with sham stimulation in individuals with migraine. Methods: A systematic search was conducted in PubMed (MEDLINE), PsycNet, and Ovid (including MEDLINE and Embase) from database inception to December 2025 in accordance with PRISMA 2020 guidelines. Studies investigating rTMS in adults with migraine and including a sham comparator were eligible for inclusion. Data regarding study design, participant characteristics, rTMS parameters, outcomes, and adverse events were extracted using a predefined template. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Results: Seven studies comprising a total of 301 participants were included. Most trials evaluated high-frequency rTMS targeting the dorsolateral prefrontal cortex. Across studies, rTMS was generally associated with reductions in migraine frequency and severity compared with sham stimulation, although results varied depending on stimulation parameters and study design. Treatment was consistently well tolerated, with only mild and transient adverse effects reported. However, considerable heterogeneity was observed in diagnostic criteria, stimulation protocols, outcome measures, and follow-up duration. Conclusions: Preliminary evidence suggests that rTMS may represent a promising and well-tolerated neuromodulatory approach for migraine management. Nevertheless, methodological variability, limited sample sizes, and concerns regarding risk of bias restrict definitive conclusions. Larger randomized controlled trials with standardized protocols and longer follow-up periods are needed to clarify the clinical role of rTMS in migraine treatment. Full article

Neuropathic pain represents a complex, prolonged pain state arising from lesions within the somatosensory nervous system. Despite significant advances in elucidating its pathophysiology, current therapeutic approaches remain largely symptomatic and frequently inadequate. MicroRNAs, a class of small non-coding RNAs that regulate gene expression post-transcriptionally, have recently emerged as critical modulators of neuronal excitability, neuroinflammation, and synaptic plasticity, which are crucial processes in the development and maintenance of neuropathic pain. This review summarizes the current evidence linking specific miRNAs to the onset and maintenance of neuropathic pain, with an emphasis on their roles in peripheral and central sensitization. The potential of miRNA-based biomarkers for diagnosis and prognostic evaluation is also highlighted. A thorough understanding of the complex miRNA regulatory networks underlying neuropathic pain could facilitate the development of novel, mechanism-based therapies and ultimately improve clinical outcomes. Full article

Articular cartilage is a highly specialized connective tissue essential for joint function, providing load-bearing capacity, shock absorption, and near-frictionless motion. Due to its avascular nature, articular cartilage has a limited intrinsic healing capacity, and focal injuries often progress to degenerative joint diseases such as osteoarthritis, leading to chronic pain and functional impairment. This review examines current and emerging scientific, clinical, and technological strategies for articular cartilage repair and regeneration, with particular emphasis on their translational relevance. This narrative review integrates data from peer-reviewed literature, clinical trial registries, and patent databases. Preclinical and clinical approaches are discussed, including orthobiologics, cell-based therapies, advanced biomaterials, and three-dimensional tissue-engineered scaffolds. Bibliometric and keyword network analyses are used to identify dominant research themes, technological trends, and emerging innovations. The findings reveal a clear paradigm shift from conventional surgical interventions, often associated with fibrocartilage formation and suboptimal biomechanical performance, to multifactorial regenerative strategies combining cells, bioactive signals, and biomimetic scaffolds designed to recapitulate the native extracellular matrix. This convergence of regenerative medicine, tissue engineering, and biomaterials science is reflected in growing clinical translation efforts and intellectual property activity. Overall, although articular cartilage repair remains a significant clinical challenge, integrated regenerative approaches show great potential for achieving durable and functional cartilage regeneration. Full article

Ankylosing spondylitis (AS) exhibits marked clinical heterogeneity that is poorly captured by conventional disease-centric analyses, hindering the development of personalized therapies. We propose a symptom-centered network pharmacology framework that directly links individual clinical symptoms to their underlying molecular mechanisms and therapeutic targets. AS- and symptom-associated genes were collected from GeneCards and prioritized using centrality analysis within protein–protein interaction networks. Symptom relevance was validated using patient-derived transcriptomic datasets. Network proximity between symptom modules and FDA-approved drug targets was assessed. A refined gene set, integrating TNF-associated neighbors and highly central nodes, was subjected to pathway enrichment analysis. Disease-centric analysis yielded a restricted 18-gene core enriched mainly in broad immune pathways. In contrast, the symptom-centered network identified 145 genes associated with specific symptoms such as inflammatory back pain and morning stiffness. Key genes, including PTEN, TLR4, JAK2, NRAS, and NR3C1, were significantly upregulated in AS patients. TNF showed local connectivity but limited global proximity, while IL17A- and JAK inhibitor-related targets were absent. A refined 24-gene module revealed enrichment in interleukin- and cytokine-mediated signaling pathways. Symptom-centered network analysis more effectively captures molecular heterogeneity in AS, providing a robust framework for symptom-specific target discovery and personalized therapeutic strategies. Full article

Intervertebral disc degeneration (IDD) is a leading cause of low back pain (LBP) and imposes a substantial social and economic burden. Current treatments mainly relieve symptoms but rarely halt or reverse disc degeneration, and key gaps remain in our understanding of its pathophysiology. Accordingly, promoting intervertebral disc regeneration (IVDR) has been proposed as a potential therapeutic aim. Immunometabolism, which refers to the bidirectional interplay between immune responses and cellular metabolism, is increasingly recognized as a key factor affecting the balance of disc homeostasis and degeneration and has become an emerging research focus. In this review, we synthesize evidence supporting a dual and context-specific role of immunometabolism in IDD and IVDR. On the one hand, certain immune cells and anabolic cytokines or growth factors may promote a regenerative microenvironment by supporting disc cell survival and extracellular matrix (ECM) synthesis. On the other hand, pro-inflammatory mediators and metabolic disorders, including oxidative stress, mitochondrial dysfunction, and lipid or amino acid imbalance, drive a catabolic cascade that accelerates ECM breakdown and cellular senescence. We summarize current knowledge regarding key immune cell subsets, cytokine networks, and metabolic pathways implicated in IDD pathogenesis and IVDR, and we discuss how these immunometabolic principles are being leveraged in emerging interventions such as stem cell-based therapies, gene therapy, and advanced biomaterials. By integrating mechanistic insights with translational advances, this review aims to clarify actionable immunometabolic targets and to inform the rational development of regenerative strategies for disc-related diseases. Full article

Introduction: Massage therapy delivers structured mechanosensory input that can influence brain function, yet the central mechanisms and potential for neuroplastic change have not been synthesized across neuroimaging modalities. This mechanistic review integrates evidence from electroencephalography (EEG), functional MRI (fMRI), and functional near-infrared spectroscopy (fNIRS) to map how massage alters human brain activity acutely and over time and to identify signals of longitudinal adaptation. Materials and Methods: We conducted a scoping, mechanistic review informed by PRISMA/PRISMA-ScR principles. PubMed/MEDLINE, Cochrane Library, Google Scholar, and ResearchGate were queried for English-language human trials (January 1990–July 2025) that (1) delivered a practitioner-applied manual massage (e.g., Swedish, Thai, shiatsu, tuina, reflexology, myofascial techniques) and (2) measured brain activity with EEG, fMRI, or fNIRS pre/post or between groups. Non-manual stimulation, structural-only imaging, protocols, and non-English reports were excluded. Two reviewers independently screened and extracted study, intervention, and neuroimaging details; heterogeneity precluded meta-analysis, so results were narratively synthesized by modality and linked to putative mechanisms and longitudinal effects. Results: Forty-seven studies met the criteria: 30 EEG, 12 fMRI, and 5 fNIRS. Results: Regarding EEG, massage commonly increased alpha across single sessions with reductions in beta/gamma, alongside pressure-dependent autonomic shifts; moderate pressure favored a parasympathetic/relaxation profile. Connectivity effects were state- and modality-specific (e.g., reduced inter-occipital alpha coherence after facial massage, preserved or reorganized coupling with hands-on vs. mechanical delivery). Frontal alpha asymmetry frequently shifted leftward (approach/positive affect). Pain cohorts showed decreased cortical entropy and a shift toward slower rhythms, which tracked analgesia. Somatotopy emerged during unilateral treatments (contralateral central beta suppression). Adjuncts (e.g., binaural beats) enhanced anti-fatigue indices. Longitudinally, repeated programs showed attenuation of acute EEG/cortisol responses yet improvements in stress and performance; in one program, BDNF increased across weeks. In preterm infants, twice-daily massage accelerated EEG maturation (higher alpha/beta, lower delta) in a dose-responsive fashion; the EEG background was more continuous. In fMRI studies, in-scanner touch and reflexology engaged the insula, anterior cingulate, striatum, and periaqueductal gray; somatotopic specificity was observed for mapped foot areas. Resting-state studies in chronic pain reported normalization of regional homogeneity and/or connectivity within default-mode and salience/interoceptive networks after multi-session tuina or osteopathic interventions, paralleling symptom improvement; some task-based effects persisted at delayed follow-up. fNIRS studies generally showed increased prefrontal oxygenation during/after massage; in motor-impaired cohorts, acupressure/massage enhanced lateralized sensorimotor activation, consistent with use-dependent plasticity. Some reports paired hemodynamic changes with oxytocin and autonomic markers. Conclusions: Across modalities, massage reliably modulates central activity acutely and shows convergent signals of neuroplastic adaptation with repeated dosing and in developmental windows. Evidence supports (i) rapid induction of relaxed/analgesic states (alpha increases, network rebalancing) and (ii) longer-horizon changes—network normalization in chronic pain, EEG maturation in preterm infants, and neurotrophic up-shifts—consistent with trait-level recalibration of stress, interoception, and pain circuits. These findings justify integrating massage into rehabilitation, pain management, mental health, and neonatal care and motivate larger, standardized, multimodal longitudinal trials to define dose–response relationships, durability, and mechanistic mediators (e.g., connectivity targets, neuropeptides). Full article

Endometriosis is traditionally conceptualized as a pelvic lesion–centered disease; however, mounting evidence indicates it is a chronic, systemic, and multifactorial inflammatory disorder. This review examines the molecular dialog between ectopic endometrial tissue, the immune system, and peripheral organs, highlighting mechanisms that underlie disease chronicity, symptom variability, and therapeutic resistance. Ectopic endometrium exhibits distinct transcriptomic and epigenetic signatures, disrupted hormonal signaling, and a pro-inflammatory microenvironment characterized by inflammatory mediators, prostaglandins, and matrix metalloproteinases. Immune-endometrial crosstalk fosters immune evasion through altered cytokine profiles, extracellular vesicles, immune checkpoint molecules, and immunomodulatory microRNAs, enabling lesion persistence. Beyond the pelvis, systemic low-grade inflammation, circulating cytokines, and microRNAs reflect a molecular spillover that contributes to chronic pain, fatigue, hypothalamic–pituitary–adrenal axis dysregulation, and emerging gut–endometrium interactions. Furthermore, circulating biomarkers—including microRNAs, lncRNAs, extracellular vesicles, and proteomic signatures—offer potential for early diagnosis, patient stratification, and monitoring of therapeutic responses. Conventional hormonal therapies demonstrate limited efficacy, whereas novel molecular targets and delivery systems, including angiogenesis inhibitors, immune modulators, epigenetic regulators, and nanotherapeutics, show promise for precision intervention. A systems medicine framework, integrating multi-omics analyses and network-based approaches, supports reconceptualizing endometriosis as a systemic inflammatory condition with gynecologic manifestations. This perspective emphasizes the need for interdisciplinary collaboration to advance diagnostics, therapeutics, and individualized patient care, ultimately moving beyond a lesion-centered paradigm toward a molecularly informed, holistic understanding of endometriosis. Full article

Background: Chronic nonbacterial prostatitis (CNP), the major subset of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), imposes a substantial global burden yet lacks satisfactory therapies. Maizibizi Wan (MZBZ) has long been used clinically for prostatitis, but its pharmacodynamic substance basis and mechanisms remain unclear. Methods: Ultra-high-performance liquid chromatography–Q-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS) coupled with Global Natural Products Social Molecular Networking (GNPS) molecular networking profiled MZBZ constituents and rat plasma–exposed prototype components and metabolites was used. Based on blood-absorbable components, network pharmacology predicted core targets/pathways; representative interactions were validated by molecular docking. A λ-carrageenan–induced CNBP rat model underwent histopathology (H&E), serum cytokine assays (TNF-α, IL-1β, IL-6/IL-17), immunohistochemistry (COX-2, TNF-α, MMP-9), and Western blotting (P-p65/p65, p-AKT/AKT, COX-2, TGF-β1, BCL2). Results: A total of 188 chemical constituents were identified in MZBZ (79 flavonoids, 38 organic acids, 30 alkaloids, 15 phenylpropanoids, 7 steroids, 4 phenylethanoid glycosides, 15 others). A total of 35 blood-absorbable components (18 prototype components, 17 metabolites) were identified, mainly involving Phase I oxidation and Phase II glucuronidation/sulfation. Network analysis yielded 54 core targets enriched in NF-κB and PI3K/AKT signaling and apoptosis. Docking indicated stable binding of key flavonoids to COX-2, NFKB1, TNF, IL-6, and BCL2. In vivo, MZBZ ameliorated prostatic inflammation, reduced serum TNF-α/IL-1β/IL-6/IL-17 (p < 0.05 or p < 0.01); decreased P-p65/p65, p-AKT/AKT, COX-2, and TGF-β1; and increased BCL2 in prostate tissue. Conclusions: MZBZ exerts anti-CNBP effects via multi-component synergy (prototypes + metabolites) that suppresses inflammatory cytokines, modulates apoptosis, and inhibits NF-κB and PI3K/AKT pathways. These findings provide a mechanistic basis and quality control cues for the rational clinical use of MZBZ. Full article

Background: Worldwide, cancer is a leading cause of morbidity and mortality, with symptoms of pain and emotional distress, associated with the disease and its treatment. Art therapy and art making are promising adjuncts to pharmacotherapy for these symptoms. However, current studies do not support replacing pharmacotherapy with these methods. Research Question: Is there evidence supporting the use of art therapy and/or art making interventions for managing cancer-related pain (primary outcome) and emotional distress (secondary outcome) among adult cancer survivors, during and following active treatment? Methods: We searched six databases, including PubMed, CINAHL, Scopus, ProQuest (library’s version), and Google Scholar, using the search terms “cancer pain” AND “art therapy” OR “art making.” Inclusion criteria included English language, peer-reviewed studies, on adult cancer survivors. The search yielded 1305 results, with 23 meeting the inclusion criteria. Because emotional distress was frequently discussed in the context of cancer-related pain in the included studies, it was added as a secondary outcome. Results: The efficacy of art therapy/art making to manage cancer-related pain and emotional distress was difficult to determine due to the heterogeneity of study designs and interventions. Of the studies reviewed in which pain was a primary outcome, eight found significant pain reductions, three found small or no effects, and three reviews described art making as a non-verbal method of communicating about pain, but did not address changes in pain levels. The terms “art therapy” and “art making” were sometimes used interchangeably. The choice of therapeutic approach was sometimes financially driven, and was also impacted by the availability of certified art therapists. Discussion: Methodological shortcomings of the existing research include small sample sizes, lack of standardized intervention protocols, and inconsistent outcome measures, underscoring the need for more rigorous and generalizable studies. Future research should consider neuroimaging evidence linking aesthetic experiences with activation of the brain’s “reward network” by utilizing fMRI to study brain activity during art therapy and art making interventions. Full article

Background/Objectives: Previous studies have demonstrated an association between migraine headache and temporomandibular joint disorders (TMDs), with a higher prevalence of TMD symptoms in patients with migraine. Methods: In this study, we conducted RNA sequencing to identify differentially expressed genes (DEGs) in the spinal trigeminal nucleus caudalis of mice with migraine-like pain and/or myogenic TMD. Results: We observed 204 upregulated and 274 downregulated genes in the comorbid migraine and TMD group compared to the control group. We identified 15 ferroptosis-related DEGs enriched in the pathways of neurodegeneration, cellular homeostasis, interleukin signaling, and pain response. Gene Ontology analysis highlighted the involvement of neuroinflammatory response and monoamine transmembrane transporter activity, while Gene Set Enrichment analysis showed enrichment in chemokine signaling, cell cycle, and calcium signaling pathways. Immune infiltration analysis identified M0 macrophages, immature dendritic cells, neutrophils, and eosinophils as key responders. Hub genes in the protein–protein interaction network included Gm7536, Rpl17, Rpl22l1, Rpl14, Rps8, Rps29, Rpl35, Gm4889, Gm11808, Rps27rt, Rps12-ps3, Rpl10-ps3, Gm9843, Oas1c, Il1b, and Serpine1, indicating their synergistic roles in such orofacial pain comorbidity. Conclusions: Our results suggest that the comorbid migraine and TMD can regulate gene expressions involving ferroptosis and immune cell responses and the identified DEGs could be targeted to develop novel therapies for this painful comorbidity. Full article

Objective: This study aimed to evaluate, through a network meta-analysis, the short- and long-term efficacy of both Western medical therapies and traditional Chinese medical therapy (acupuncture) in improving symptoms of shoulder pain. Methods: A comprehensive computer-based search was conducted in Embase, Cochrane Library, Web of Science, and PubMed databases for randomized controlled trials (RCTs) related to Western and Chinese medical treatments for shoulder pain measured by visual analogue scale (VAS) scores. All researchers independently screened and selected studies, extracted data, and assessed the risk of bias. Studies that met quality standards were analyzed using Stata 16.0 and Review Manager 5.4 software. Results: A total of 269 articles were retrieved, and 15 were ultimately included in the network meta-analysis, covering nine types of Western and Chinese medical therapies. The total sample size was 1114 cases, with 557 in an experimental group and 557 in a control group. In terms of reducing VAS scores at 4 weeks after treatment, sham acupuncture was significantly less effective than acupuncture (MD: 19.39; 95% CI: 0.66–38.12), indicating that acupuncture had a better short-term effect on pain relief at 4 weeks. In terms of reducing VAS scores at 12 weeks after treatment, sodium hyaluronate (hyaluronate) was more effective than physical therapy (PT) in reducing long-term pain (MD: −19.57; 95% CI: −37.23–−1.90); suprascapular nerve block (SSNB) (MD: −9.11; 95% CI: −16.02–−2.20) and arthroscopic capsular release (MD: −16.07; 95% CI: −30.16–−1.97) were also more effective than PT. The top three treatments in terms of clinical efficacy for painful shoulder conditions were hyaluronate, SSNB, and arthroscopic capsular release. Conclusions: For the treatment of shoulder pain, hyaluronate, SSNB, and arthroscopic capsular release showed greater potential long-term efficacy in pain reduction than PT, with hyaluronate showing the best effect. Full article

Objectives: Shengji Yuhong Ointment (SJYHO) is a classic Traditional Chinese Medicine prescription used for refractory wounds, yet its systemic pharmacological mechanisms remain unclear. This study aimed to identify its key active compounds and develop a simplified, effective topical formulation. Methods: We employed an integrated approach, combining network pharmacology and machine learning to screen the key constituents and core targets of SJYHO. The lead compound, glycyrrhizic acid, was formulated into a hydrogel (GA-Gel). Its therapeutic efficacy was evaluated in a full-thickness excisional wound model in Sprague-Dawley rats over 21 days, assessing healing kinetics, histology, and pain behavior. The interaction between glycyrrhizic acid and the identified target PPIA, along with its immunomodulatory effects, was validated through molecular docking, molecular dynamics simulation, and RT-qPCR. Results: Our integrated analysis identified PPIA as the core target and glycyrrhizic acid as a key bioactive component of SJYHO. Animal experiments demonstrated that GA-Gel significantly accelerated wound closure, which was driven by its multi-faceted actions: reducing inflammation, promoting collagen deposition, alleviating pain, and modulating late-stage angiogenesis. Mechanistically, we confirmed that glycyrrhizic acid stably binds to PPIA. Furthermore, GA-Gel treatment mediated wound immune infiltration by specifically regulating CD8⁺ T cells, neutrophils, and memory B cells, an effect that was dependent on PPIA targeting. Conclusions: This study demonstrates that glycyrrhizic acid, formulated as GA-Gel, recapitulates the wound-healing benefits of SJYHO by specifically targeting PPIA and modulating the immune microenvironment. Our findings not only elucidate a key mechanistic pathway but also present GA-Gel as a rationally designed, clinically translatable therapy for acute and chronic wounds. Full article