BackgroundSynovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare autoinflammatory disorder characterized by osteoarticular and cutaneous manifestations. While tumor necrosis factor-alpha (TNF-α) inhibitors such as adalimumab are increasingly used for refractory cases, some patients exhibit inadequate response. Janus kinase (JAK) inhibitors have emerged as a potential alternative, but data on the selective JAK1 inhibitor upadacitinib in SAPHO syndrome are lacking.Case summaryAn 18-year-old male presented with a 7-year history of recurrent facial acne since 2016. Whole-body bone scintigraphy revealed focally increased radiotracer uptake in the right clavicle, consistent with SAPHO syndrome. Initial treatment of acne with adapalene gel combined with oral minocycline failed to improve skin symptoms, leading to the decision to ultimately pursue biologic therapy. After four months of adalimumab therapy, the patient initially showed improvement in chest pain and dermatitis but subsequently experienced paradoxical worsening of facial acne accompanied by erythema and pruritus. No improvement was observed after an additional four weeks of continued adalimumab treatment. Following a transition to upadacitinib, facial lesions improved within 4 weeks and achieved marked resolution by 8 weeks.ConclusionThis report of upadacitinib in SAPHO syndrome demonstrates its rapid and substantial efficacy in a patient refractory to adalimumab. Upadacitinib may represent a promising treatment option for difficult-to-treat SAPHO syndrome, particularly in cases with inadequate response to TNF-α inhibition.

Objective This study aimed to explore the main pharmacological components and mechanisms of action of Tripterygium wilfordii Hook.f.in the treatment of synovitis,acne,pustulosis,hyperostosis,osteitis(SAPHO)syndrome through network pharmacology and molecular docking technology. Methods The active ingredients and gene targets of Tripterygium wilfordii Hook.f.were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the disease targets of SAPHO syndrome were obtained from the Gene Cards database.Venny plots were drawn,and the intersecting genes were selected as potential therapeutic targets;Cytoscape 3.9.0 software was used to create target maps;string construction of PPI protein network was performed;Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed using the Database for Annotation,Visualization,and Integrated Discovery(DAVID)to predict the targets and pathways of active ingredients from Tripterygium wilfordii for treating SAPHO syndrome;and Autodock4.2.6 software was used for molecular docking validation and display of active ingredients and targets. Results Six active ingredients from Tripterygium wilfordii Hook.f.were screened,corresponding to 136 targets,73 disease targets related to SAPHO syndrome,and 4 intersecting gene targets,namely VEGFA,TNF,TP53,and CXCL8.The pathways involved mainly included the PI3K/AKTsignaling pathway and the mitogen-activated protein kinase(MAPK)signaling pathway.Among them,molecular docking showed that the active ingredients of Tripterygium wilfordii Hook.f.B2 and Cinnamomum comptothecin from Sophora alopecuroides have good binding activity with the core target of SAPHO syndrome. Conclusion The system explains the complex relationship between"drug-target-pathway-disease"in the treatment of SAPHO syndrome with Tripterygium wilfordii Hook.f.,providing a theoretical basis for the use of Tripterygium wilfordii Hook.f.in the treatment of SAPHO syndrome.

SAPHO syndrome is a rare autoinflammatory disorder with osteoarticular and cutaneous involvement. Paradoxical skin lesions have been reported during treatment with tumor necrosis factor-α (TNF-α) inhibitors. We describe a 42-year-old man with a 6-year history of SAPHO syndrome presenting with chronic sternoclavicular and lumbosacral pain and sterile pustules on the lower extremities. Conventional therapy with etoricoxib and methotrexate improved musculoskeletal symptoms but failed to resolve skin lesions, while adalimumab treatment led to progressive worsening of cutaneous manifestations. Following a switch to upadacitinib (15 mg once daily), rapid improvement of skin lesions and sustained control of musculoskeletal symptoms were achieved without adverse events. This case suggests that Janus kinase inhibition may represent a therapeutic option for TNF-α inhibitor–induced paradoxical skin lesions in SAPHO syndrome.

BackgroundExcessive osteoclast fusion and activation are central drivers of bone erosion in inflammatory osteopathies, which are closely linked to immune dysregulation. Wilforine, a natural compound, exhibits immunomodulatory and therapeutic potential, yet its precise mechanism of action—particularly its influence on the osteoclast membrane microenvironment and associated immune signaling—remains incompletely understood.MethodsWe employed a multi-level strategy combining in vivo and in vitro functional validation with systematic multi-omics analysis. The in vivo efficacy of Wilforine was assessed in a Pstpip2cmo mouse model via Micro−CT and histopathology. In vitro studies utilized osteoclast culture, TRAP staining, scanning electron microscopy, and immunofluorescence to evaluate cell fusion and protein localization. Preliminary target prediction was conducted using network pharmacology. The core mechanism was elucidated through integrated proteomics and transcriptomics, followed by targeted functional validation including β−cyclodextrin−mediated lipid raft disruption and immune−related pathway analysis.ResultsWilforine significantly alleviated bone erosion, marrow edema, and inflammatory infiltration in vivo, and potently inhibited osteoclast multinucleation in vitro. Multi-omics profiling revealed that Wilforine broadly reversed disease-associated dysregulation, specifically upregulating cholesterol metabolism and glycosphingolipid biosynthesis pathways while modulating key immune-inflammatory networks such as NF−κB. This systemic remodeling of the lipid metabolic landscape was functionally linked to the disruption of membrane lipid raft integrity—critical platforms for immune receptor signaling. Consequently, the raft-dependent localization and function of key fusion proteins (CD9, DC−STAMP) were impaired. Mechanistically, Wilforine exerted these effects by suppressing the JAK−STAT signaling pathway, a central regulator of immune and inflammatory responses, leading to the downregulation of the essential lipid raft scaffold protein Stomatin.ConclusionThis study defines a novel immunometabolic mechanism wherein Wilforine inhibits osteoclast fusion and bone resorption by reprogramming cellular lipid metabolism and disrupting the “JAK−STAT – Stomatin – Lipid Raft” functional axis. It highlights lipid rafts as a viable immunomodulatory microenvironment in bone disorders and provides a strong multi−omics−supported rationale for developing Wilforine as a bone−targeted immunotherapeutic agent.

Electrical stimulation therapies have become pivotal interventions for managing refractory movement disorders. However, the rapidly expanding and fragmented body of literature necessitates a macroscopic evaluation to identify global collaborative networks and emerging scientific frontiers. Consequently, this study conducted a comprehensive visualization analysis of research trends and hotspots in this domain to delineate the evolutionary trajectory and guide future therapeutic developments. Publications from 2016 to 2025 were retrieved from the Web of Science Core Collection and PubMed using keywords such as movement disorders, deep brain stimulation, and neuromodulation. Selection criteria mandated English-language clinical articles and reviews investigating electrical stimulation, while excluding purely pharmacological studies. Bibliometric mapping was performed utilizing CiteSpace VOSviewer, the bibliometrix R package, and Microsoft Excel. A total of 2,944 publications were retrieved from 553 journals by 13,489 authors from 489 countries/regions across six continents. The United States contributed the highest volume, followed by Germany and China. The University of Toronto emerged as the most prolific and collaborative institution ahead of Harvard Medical School and the University of Florida. The journal Movement Disorders ranked first in both publication productivity and co-citation frequency. Furthermore, Lozano AM and Fasano A were identified as the most productive authors, while Deuschl G and Benabid AL represented the foundational co-cited authorities. Thematic analysis indicates that research focuses primarily on deep-brain stimulation targeting the subthalamic nucleus for Parkinson’s disease. Crucially, emerging keywords, including plasticity, substantia nigra balance, and dynamics, demonstrate a definitive scientific shift. This transition moves away from static symptom management toward investigating complex neural circuit mechanisms and optimizing adaptive closed-loop neuromodulation to address refractory symptoms. This analysis highlights a major shift in electrical stimulation research from open-loop validation toward individualized connectomics and mechanism-based neurorehabilitation. Despite robust growth in publications, structural isolation persists in emerging high-productivity regions, necessitating multinational collaboration for future trials. Ultimately, harnessing targeted neuroplasticity and adaptive technologies will drive sustained functional neurorestoration and improve long-term patient outcomes.

Small interfering RNA (siRNA) hydrogels constitute an advanced therapeutic paradigm that synergizes the precision of gene silencing with engineered biomaterial carriers to overcome critical delivery barriers, including enzymatic degradation, poor cellular uptake, and systemic toxicity. This comprehensive review systematically examines: Fundamental design principles of stimuli-responsive hydrogels (thermal, reduction-sensitive, pH-triggered, and magnetic systems) enabling spatiotemporal siRNA release; Therapeutic efficacy across diverse pathologies—organ-specific tumor interventions (digestive, reproductive, respiratory systems), regenerative applications (bone/cartilage repair, spinal cord regeneration), and inflammatory diseases (arthritis, dermatitis, ocular/intestinal disorders); Translational challenges in delivery efficiency, long-term biosafety, and clinical scalability. Current research progress indicates that hydrogel-encapsulated siRNA achieves targeted modulation of pathological pathways through microenvironment-adaptive functionality, significantly enhancing local bioavailability while minimizing off-target effects. Despite promising preclinical outcomes, limitations persist in resolving biological barrier penetration, release kinetics-disease progression alignment, and carrier immunogenicity. This review underscores the transformative potential of siRNA hydrogels in redefining precision medicine and delineates critical pathways for bridging laboratory innovation to clinical practice.

Chronic wound healing is a significant challenge in diabetes. Puerarin is an active compound extracted from the traditional Chinese medicine Pueraria lobata. Puerarin has been used in the treatment of diabetes and derives benefits from its antioxidant, anti-inflammatory, antibacterial, and pro-angiogenesis properties, but its efficacy is hampered by poor water solubility and bioavailability. In this study, we designed a polyvinyl alcohol (PVA)–borax–puerarin (BP) hydrogel system that self-assembled via boronic ester bonds. The BP hydrogel exhibited exceptional physical characteristics, including adaptability, injectability, plasticity, self-healing capabilities, and robust compressive strength, as well as good biocompatibility. In the chronic wound diabetic rats model, the BP hydrogel significantly accelerated wound healing, as evidenced by hematoxylin and eosin (HE) staining, as well as Masson and picrosirius red (PSR) staining. RNA–sequencing and multiple immunohistochemistry (mIHC) analyses revealed that the BP hydrogel exerts a therapeutic effect by modulating macrophage polarization, promoting angiogenesis, and regulating collagen remodeling. Our findings suggest that the BP hydrogel represents a promising wound dressing and holds great potential for clinical applications in acute and chronic wound management.

Diabetic wounds significantly impair the life quality of patients and impose substantial economic burdens on both individuals and healthcare systems. Hydrogel dressings, owing to their multifunctional properties, have emerged as a promising strategy for wound management. By integrating gelation capabilities with inherent pharmacological activities, natural products are frequently employed in the development of hydrogel formulations. Herein, we developed a hydrogel with Bletilla striata polysaccharide (BSP), carboxymethyl chitosan (CMCS) and cinnamaldehyde (CA) for the management of diabetic wounds. The hydrogel was fabricated via Schiff base reaction and hydrogen bonding. It exhibited excellent biocompatibility and potent antibacterial activity in vitro. In a diabetic rat full-thickness skin wound model, the hydrogel significantly accelerated wound healing by promoting re-epithelialization, collagen deposition and angiogenesis. These results highlight the therapeutic potential of polysaccharide-based hydrogel for the treatment of diabetic wounds.

OBJECTIVE:The primary objective of this study was to investigate the modulation of intestinal flora composition in a murine model of ulcerative colitis (UC) through the application of electroacupuncture. This study also aimed to analyze the role of specific microbial taxa and to identify the key regulatory targets and pathways involved in this modulation. METHODS:A UC model was established in mice through the administration of a 5% dextran sodium sulfate (DSS) solution. Subsequently, UC mice underwent electroacupuncture treatment, with mesalazine serving as a positive control. The electroacupuncture group received treatment at the bilateral "Shangjuxu" acupuncture points, while the mesalazine group was administered mesalazine at a dosage of 0.5 g/kg via gavage. Interventions were conducted from days 5 to 9 of the experimental period. The weight, disease activity index (DAI) scores, and colon lengths of the mice across all groups were compared. Hematoxylin-eosin (HE) staining was utilized to assess the morphological characteristics of colon tissue, thereby validating the efficacy of electroacupuncture in the UC model. Additionally, 16S rDNA high-throughput sequencing was employed to analyze alterations in the intestinal flora present in the feces of the UC model mice. RESULTS:Compared to the model group, the DAI scores of mice in the electroacupuncture group were significantly reduced on days 7 and 9 of the experiment (P < 0.05; P < 0.01). HE staining revealed a marked reduction in morphological disruption and inflammatory infiltration within the colon tissue of the electroacupuncture group relative to both the model and mesalazine groups. Results from linear discriminant analysis effect size and Wilcoxon rank-sum test demonstrated a significant increase in the abundance of genera, such as Roseburia, in the electroacupuncture group. Furthermore, the alpha diversity of the intestinal flora exhibited an increase. Predictions regarding intestinal microbial function indicated that pathways, such as RNA transport and glycerophospholipid metabolism, were significantly diminished in the model group compared to the control group (P < 0.05), while these pathways were significantly enhanced in the electroacupuncture group relative to the model group (P < 0.01). CONCLUSION:Electroacupuncture effectively regulated both the structure and function of intestinal flora in UC mice. The genus Roseburia may serve as a critical therapeutic target for electroacupuncture in the modulation of intestinal flora in UC. Additionally, lipid metabolism and RNA transport may represent key pathways through which electroacupuncture exerts its regulatory effects on intestinal flora.

Ethnopharmacological relevance Celastrol, a bioactive compound from Tripterygium wilfordii Hook.f., is known for its anti-inflammatory and immunomodulatory effects, but its immunotoxicity is underexplored. This study investigates the mechanisms of celastrol-induced immunotoxicity, focusing on the PI3K-Akt signaling pathway, a key regulator of immune function.Materials and methods An integrative approach combining network toxicology, molecular docking, and experimental biology identified molecular targets in celastrol-induced immune dysfunction. Network toxicology mapped key pathways, and molecular docking predicted interactions with immune-related proteins. High-dose celastrol (10 mg/kg) was administered to C57BL/6J mice, followed by a histopathological analysis of the thymus and spleen. RNA-Seq evaluated gene expression in immune pathways, and IHC/mIHC validated PI3K-Akt signaling pathway protein expression.Results Network toxicology identified the PI3K-Akt signaling pathway as a key target of celastrol's immunotoxic effects. High-dose celastrol caused histopathological damage in the thymus and spleen, including lymphocyte depletion and immune cell infiltration. RNA-Seq showed upregulation of critical genes in the PI3K-Akt signaling pathway (Egfr, Pik3c, Akt3), linked to cell proliferation and survival. IHC confirmed increased expression of EGFR, AKT, PIK3, and mTOR, with decreased PTEN. mIHC revealed elevated macrophage activation and inflammation. In contrast, low-dose celastrol suppressed PI3K-Akt signaling by downregulating mTOR, indicating dose-dependent modulation of immune function.Conclusion Our study demonstrates the dose-dependent immunotoxic effects of celastrol, which is toxic in high doses caused by activation of the PI3K-Akt signaling pathway, while low doses offer protection by blocking this signaling pathway. These findings emphasize the importance of dose selection in therapeutic and safety contexts, enhancing understanding of celastrol's biological effects and its clinical potential in immune-related diseases.

To study the clinical, imaging, and computed tomography (CT)—guided biopsy pathology of patients with infectious sacroiliitis (ISI). We retrospectively analysed 135 patients diagnosed with ISI between 2008 and 2020, comprehensively evaluating clinical characteristics, laboratory test outcomes, pathological examination results, and magnetic resonance images (MRI). Among the 135 patients with ISI, 90 (66.7

Background: With the continuous development of Terahertz technology and its high sensitivity to water, Terahertz technology has been widely applied in various research areas within the field of biomedicine, such as research onskin wounds and burns, demonstrating numerous advantages and potential. Objective: The aim of this study is to summarize and conclude the current research status of Terahertz radiation in skin wounds, burns, and melanoma. Additionally, it seeks toreveal the development status of Terahertz in skin wound models and analyze the short comings of Terahertz in detecting such models at the present stage. Methods: We retrieved relevant literature published from the inception of the Web of Science and CNKI databases up to 2024. The search terms included "THz," "Terahertz," "skin," "wound," "burn," and "melanoma." High-quality articles were included after rigorous screening. Results and Conclusions: This review explores the progress of terahertz radiation technology in the treatment and diagnosis of skin wounds and other related diseases. The results of its interaction with skin tissues provide valuable insights for future research. Terahertz radiation imaging has proven to be effective in assessing burn severity, capturing changes in edema, measuring exudates in dressings, assisting in burn grading and detection, and quantifying wound changes over time. Terahertz technology offers significant advantages in trauma assessment, which has accelerated its development and adoption in this field. (4) However, fs-THz radiation has been found to have the potential drawback of affecting wound healing. This finding necessitates careful consideration before application, and further research is warranted to explore its role in burn assessment and other medical applications.

Objective: Bone defects present a significant clinical challenge, often requiring surgical intervention due to delayed healing. Terahertz (THz) radiation, a noninvasive physical energy-based therapy, has shown potential in promoting bone regeneration through biomolecular interactions. This study aims to evaluate the therapeutic efficacy of THz irradiation in enhancing bone repair using a pre-clinical rat tibial fracture defect model. Methods: A standardized tibial bone defect model was created in rats, with daily THz irradiation (0.1 THz, 20 min/session) administered continuously for 28 days. Micro-computed tomography (CT) evaluations were performed weekly throughout the study period, while histological assessments (hematoxylin and eosin [HE] and Masson staining), vascular endothelial growth factor (VEGF) immunohistochemistry, and serum biomarker analyses were exclusively conducted at the 28-days endpoint. Micro-CT imaging, histopathological staining, and tyramide signal amplification analyses were conducted to assess bone volume fraction, collagen deposition, and angiogenesis. Blood biochemical markers were also evaluated to determine systemic metabolic effects. Results: By week 4, the THz-treated group demonstrated a higher new bone formation compared with control group. Micro-CT analysis revealed significantly improved cortical continuity and bone volume fraction at weeks 3 and 4 (p < 0.05). HE and Masson staining showed enhanced collagen alignment and trabecular organization. The IF test indicated increased VEGFA expression in local new bone (p < 0.01), suggesting augmented angiogenesis. No significant changes were observed in serum biochemistry markers, indicating localized rather than systemic effects. Conclusions: THz radiation effectively accelerates bone defect healing by enhancing osteoblast activity and vascularization without systemic metabolic alterations. These findings highlight the potential of THz therapy as a novel, noninvasive approach for bone regeneration, warranting further research for clinical translation.

Numerous traditional Herbal medicine (THM) formulas have demonstrated their effectiveness during long-term clinical practices worldwide, offering a rich repository for the discovery of new drug and functional biomaterials. Consequently, the development of therapeutic supramolecular hydrogels based on plant-derived bioactive molecules has garnered significant attention in the field of new drug development. In this study, we developed a well-defined orally supramolecular drug derived from the classic Ma-Xing-Shi-Gan decoction (MXSGD) which has been widely used in China for the treatment of COVID-19 symptoms and acute infectious diseases. The four representative chemical components of MXSGD-pseudoephedrine, amygdalin, glycyrrhizic acid, and Ca2+-co-assembled into quaternary carrier-free supramolecular structure (Quad hydrogel) through non-covalent interactions. This Quad hydrogel exhibited well thermal reversibility, injectable performance, mechanical strength, sustained release, intestinal retention, enhanced drug absorption, and biocompatibility by oral administration. Moreover, Quad hydrogel significantly inhibited the activation of lipopolysaccharides (LPS)-induced MAPK and NF-κB signaling pathway, thereby synergistically relieving fever in rats more effectively than the original MXSG decoction, equivalent pseudoephedrine (PSE) monomer and the physical mixture four components (Quad mix). In summary, this study provides a novel strategy for developing new supramolecular drug based on classic THM formulas, as well as integrating THM with modern technologies.

Background: Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition with limited treatment efficacy. Alternating current electroacupuncture (AC-EA) represents a novel neuromodulatory approach, though its mechanisms-particularly its influence on the gut-brain axis-remain underexplored. Methods: We investigated the neurobehavioral and microbiological effects of AC-EA in a rat model of PTSD induced by single prolonged stress. Animals received AC-EA at Baihui (GV20) and Mingmen (GV4) acupoints with varying parameters (0.5 mA/20 Hz, 1 mA/20 Hz, and 1 mA/2 Hz). Behavioral tests (open field test, elevated plus maze), histopathological assessments, immunofluorescence for TLR4, and 16S rRNA sequencing of gut microbiota were performed. Results: AC-EA at 1 mA/2 Hz significantly improved exploratory behavior and reduced anxiety-like responses (p < 0.05). This regimen also restored neuronal integrity in the hippocampus and cortex and reversed PTSD-induced gut dysbiosis, enriching beneficial genera such as Ligilactobacillus. Furthermore, AC-EA downregulated hepatic TLR4 expression, indicating suppression of neuroinflammatory signaling. Conclusions: Our findings demonstrate that AC-EA exerts neuromodulatory and microbiota-rebalancing effects via the gut-brain axis, highlighting its potential as a non-invasive therapeutic strategy for PTSD and related brain health disorders.

Cardiovascular diseases (such as myocardial infarction and arrhythmia) induce cardiomyocyte death and disrupt the electrophysiological microenvironment. Traditional insulating repair materials lack conductivity and fail to reconstruct electrical conduction networks, potentially triggering secondary arrhythmias. Bioelectric stimulation materials (BSMs), which integrate conductive components to confer electrical activity upon biomaterials, have emerged as a promising strategy in cardiovascular regenerative medicine. This article systematically reviews the design and application of BSMs within the cardiovascular system, focusing on conductive polymers and nanomaterial composites for constructing electroactive functional systems. Key applications include: cardiac tissue repair and regeneration, myocardial infarction therapy, enhanced electrical signal transmission, development of bioelectronic devices, and in vitro cellular modulation. By integrating cross-scale material design with multidimensional application scenarios, this study offers insights for overcoming the limitations of traditional materials and advancing cardiovascular regenerative medicine toward electroactive precision repair.

Journal Article Accepted manuscript The Silent Stone Armor Beneath the Golden Bell: A Severe Case of Calcinosis Cutis in Dermatomyositis Get access Chen Li, Chen Li Department of Rheumatology and Immunology, Peking University International Hospital, Beijing, ChinaDepartment of Rheumatology, Fangshan Hospital, Beijing University of Chinese Medicine, Beijing, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Shao-hui Geng, Shao-hui Geng School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Shu-han Yang, Shu-han Yang School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Hong-xu Liu, Hong-xu Liu School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Fu-wen Deng, Fu-wen Deng School of nursing, Beijing University of Chinese Medicine, Beijing, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Sheng-guang Li Sheng-guang Li Department of Rheumatology and Immunology, Peking University International Hospital, Beijing, China Corresponding author: Sheng-guang Li, Department of Rheumatology and Immunology, Peking University International Hospital, Beijing, China; E-mail: [email protected] Search for other works by this author on: Oxford Academic PubMed Google Scholar Rheumatology, keaf012, https://doi.org/10.1093/rheumatology/keaf012 Published: 07 January 2025 Article history Received: 02 October 2024 Revision received: 09 December 2024 Accepted: 20 December 2024 Published: 07 January 2025

BACKGROUND:Bone fracture is a partial or complete break in the continuity of a bone, which poses a significant healthcare burden. It is important to discover a novel method to stimulate and speed-up the healing of bone fractures. AIM:This study aimed to investigate the effects and mechanisms of alternating current (AC) in promoting bone fracture healing. METHODS:A rabbit bone fracture model was used. X-ray and Micro-CT evaluated fracture healing, while HE staining and immunohistochemistry assessed morphological changes. In vitro, pre-osteoblastic cells were tested with alizarin red S staining and alkaline phosphatase (ALP) activity. RNA-seq analysis explored potential mechanisms. RESULTS:X-ray evaluation showed that alternating current stimulation (ACS) promoted bone formation and shaping by day 14 post-treatment. Micro-CT results revealed significant new bone formation as early as day 3 and day 7 (p < 0.05). HE staining indicated more trabecular bone formation in the ACS group compared to the model group at days 7 and 14. Immunohistochemistry showed higher expression of BMP-2 and VEGF in the ACS group by day 7. In vitro, ACS enhanced osteogenic differentiation, increasing calcified nodule formation and ALP activity. Gene expression analysis demonstrated significant changes in key osteogenic genes, confirmed by multiple immunohistochemical staining. CONCLUSIONS:ACS may be a novel method for treating bone fractures more rapidly, significantly relieving the patient's burden, particularly in the early stages of bone healing.

BACKGROUND:SAPHO syndrome is recognized as a rare entity with damage to skin and bones due to inflammation. Currently, the treatment for SAPHO syndrome is still a challenge in clinical practice. In this study, an integrated transcriptomics and network pharmacology approach was applied to explore the therapeutic effect and mechanism of Wang-Bi tablet (WBT) on SAPHO syndrome.METHODS:The main components of WBT and their targets, as well as the targets of SAPHO syndrome, were collected from databases. Network visualization was performed using Cytoscape software. The GO and KEGG enrichment analysis was executed by David dataset. Then, the molecular mechanism of WBT improving SAPHO syndrome was validated by transcriptomics of peripheral blood neutrophils in SAPHO syndrome. Finally, the above results were validated by molecular docking.RESULTS:The Network Pharmacology results showed there are 152 core targets for WBT treatment on SAPHO syndrome. RNA-seq data showed 442 differentially expressed genes (DEGs) in peripheral blood neutrophils of SAPHO patients. Intriguingly, NIK/NF-kappaB-, MyD88-dependent toll-like receptor-, and MAPK pathway were included in the enrichment results of network pharmacology and RNA-seq. Moreover, we verified that the core components of WBT have good affinity with the core targets of NIK/NF-kappaB-, MyD88-dependent toll-like receptor-, and MAPK pathway by molecular docking.CONCLUSIONS:This study illustrated that the possible mechanisms of WBT against SAPHO syndrome may be related to NIK/NF-kappaB-, MyD88-dependent toll-like receptor-, and MAPK pathway, and further experiments are needed to prove these predictions.