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Published Research PapersFiltered: Year 2026 • Vol 1902 • 30

Showing 18 of 200 peer-reviewed papers with full Graphical Abstracts.

Original ResearchVol 1902, Issue 30 • pp. 100-112DOI: 10.12307/2026.21438• Jan 15, 2026

Osteoarthritis characteristic genes and prediction of targeted food-medicine homology traditional Chinese medicine: bioinformatics analysis and kinetic simulation

Authors: LI Zhengpeng, SHAO Weigang, ZENG Hao, XIANG Kelin, ZHANG Botao, ZOU Shunyi, CHEN Sheng, QI Wen

BACKGROUND: Early diagnosis and treatment of osteoarthritis remain a significant challenge due to the lack of highly specific biomarkers. OBJECTIVE: To screen characteristic genes of osteoarthritis, predict potential food-medicine homology traditional Chinese medicine and their core components, and validate their therapeutic potential through molecular docking and molecular dynamics simulations. METHODS: This study is based on three datasets (GSE55235, GSE169077, and GSE55457) from the GEO database, including a total of 25 normal samples and 26 osteoarthritis samples. It combines genes extracted from the eQTL database as exposure factors, and osteoarthritis data from the IEU openGWAS database (407,746 samples) as outcome factors. Core biomarkers were identified using least absolute shrinkage and selection operator regression, random forest, and support vector machine algorithms. CIBERSORT was used to evaluate immune infiltration characteristics and single-gene gene set enrichment analysis was performed. Potential traditional Chinese medicines were predicted using Coremine Medical and HERB databases, and food-medicine homology traditional Chinese medicines and their core components were screened, followed by molecular docking and molecular dynamics simulations. RESULTS AND CONCLUSION: ① Two genes, glucose transporter 3 (GLUT3) and atypical chemokine receptor 1 (ACKR1), were identified as characteristic genes of osteoarthritis, showing good diagnostic efficacy (AUC > 0.8) and involvement in metabolic regulation, cell signal transduction, and inflammatory responses, closely related to glucose metabolism, immune regulation, and inflammatory signaling pathways. ② Seven food-medicine homology traditional Chinese medicines were screened, including Cornus officinalis, Perilla frutescens, Ganoderma lucidum, Gastrodia elata, bitter almond, clove, and Rehmannia glutinosa, with core components β-sitosterol and stigmasterol. Molecular docking and dynamics simulations showed that stigmasterol had the best affinity with GLUT3 and the complex exhibited high stability. ③ This study systematically reveals the key roles of GLUT3 and ACKR1 in the pathogenesis of osteoarthritis, preliminarily validates the possibility of food-medicine homology traditional Chinese medicines intervening in the pathological process of osteoarthritis through multi-target and multi-pathway mechanisms, providing new molecular evidence for early diagnosis and targeted therapy, as well as theoretical support for prevention and treatment strategies. This research, from the perspective of traditional Chinese medicine and modern molecular biology, can provide a reference for the clinical application of traditional Chinese medicine in osteoarthritis.

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Osteoarthritis characteristic genes and prediction of targeted food-medicine homology traditional Chinese medicine: bioinformatics analysis and kinetic simulation

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Original ResearchVol 1902, Issue 30 • pp. 100-112DOI: 10.12307/2026.21434• Jan 15, 2026

Potential targets and drug prediction for gout: identification of druggable genes

Authors: Tian Xuanhe, Tong Siyu, Teng Fei, Zhong Shuai, Zhao Xiaohu, Zhang Yuya, Liu Yuan, Jiang Ping

BACKGROUND: Existing pharmacological treatments for gout are frequently limited by substantial side effects, underscoring the urgent need to discover novel therapeutic targets and develop more targeted drugs. OBJECTIVE: To identify genetic targets for gout, and to predict promising therapeutic compounds as well as traditional Chinese medicines by integrating druggable gene datasets with Mendelian randomization and colocalization analysis approaches. This work will lay a foundation for in-depth exploration of the pathogenesis of gout in the Chinese population, and provide insights for the clinical management and development of new targeted drugs. METHODS: Gout-related datasets were obtained from the Finnish database FinnGen R11. Blood expression quantitative trait loci data were obtained from the GWAS catalog website developed by the MRC Integrative Epidemiology Unit at the University of Bristol. Mendelian randomization analysis was performed to identify potential targets; colocalization analysis was used to identify key susceptibility genes for gout. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were used to explore gene functions, and protein-protein interaction networks were used to screen closely interacting targets. The Drug-Gene Interaction Database developed by Washington University School of Medicine in St. Louis was used to predict compounds with potential therapeutic effects. Molecular docking was used to predict the binding degree of compounds to core targets. The Coremine Medical database founded by PubGene was used to predict traditional Chinese medicines related to core genes. All databases used are public resources. A gout cell model was established using monosodium urate crystal-induced RAW264.7 cells to preliminarily verify the expression of key genes and the intervention effect of compounds. CCK-8 assay and cell invasion assay were used to screen safe doses and optimal administration concentrations. ELISA was used to measure inflammatory factor levels, and real-time fluorescence quantitative reverse transcription PCR was used to detect mRNA expression of key targets and pathways. RESULTS AND CONCLUSION: (1) Mendelian randomization analysis identified 40 potential gene targets significantly associated with gout; colocalization analysis identified Jun proto-oncogene as a key susceptibility gene for gout; protein-protein interaction network showed that Jun proto-oncogene, mitogen-activated protein kinase 3, and 3-hydroxy-3-methylglutaryl-CoA reductase had close interactions. (2) Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results showed that potential targets mainly regulate mitogen-activated protein kinase, tumor necrosis factor, ErbB, interleukin-17, hypoxia-inducible factor 1, Toll-like receptor and other signaling pathways, and intervene in positive regulation of extracellular signal-regulated kinase 1/2 cascade, glutathione metabolism, ubiquitin protein regulation and other processes. (3) Based on potential targets, 372 compounds with potential intervention effects were predicted, including capsaicin, 5,6-benzoflavone, L-glutamic acid, quercetin, honokiol, kaempferol, cinnamaldehyde, and andrographolide. (4) Molecular docking showed that capsaicin and 5,6-benzoflavone had high binding affinity with core targets such as Jun proto-oncogene. (5) 79 potential targeted traditional Chinese medicines were predicted, including Atractylodes, Magnolia officinalis, Smilax glabra, Alisma orientale, and Salvia miltiorrhiza, with efficacy mainly concentrated in clearing heat and detoxifying, promoting blood circulation and removing blood stasis, and resolving phlegm and dampness. (6) In cell experiments, CCK-8 and cell invasion assay results showed that the optimal safe dose of capsaicin was 50 μmol/L. In the model group, the expression of key gene Jun proto-oncogene was significantly upregulated, and capsaicin could significantly downregulate the mRNA expression of Jun proto-oncogene and mitogen-activated protein kinase pathway-related genes such as c-Jun N-terminal kinase, extracellular signal-regulated kinase 1/2, and p38, and reduce the levels of interleukin-6, interleukin-1β, and tumor necrosis factor α in cell supernatant. (7) Data mining results suggest that compounds such as capsaicin and 5,6-benzoflavone and traditional Chinese medicines such as Atractylodes and Smilax glabra may exert therapeutic effects on gout by intervening in targets such as Jun proto-oncogene and mitogen-activated protein kinase 3, regulating tumor necrosis factor, Th-17, hypoxia-inducible factor 1 and other pathways, and mitogen-activated protein kinase cascade, protein ubiquitination, and glutathione metabolism. Among them, the key susceptibility gene JUN can serve as a potential diagnostic marker for gout. Treatment methods mainly focusing on clearing heat and detoxifying combined with promoting blood circulation and removing blood stasis can be key to gout treatment. (8) Cell experiments preliminarily verified the expression of JUN gene and mitogen-activated protein kinase pathway in gout cell model and the intervention effect of capsaicin, providing a basis and foundation for the next step of gout diagnosis and treatment targets and new drug development.

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Potential targets and drug prediction for gout: identification of druggable genes

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Original ResearchVol 1902, Issue 30 • pp. 100-112DOI: 10.12307/2026.21441• Jan 15, 2026

Bibliometric analysis of exercise therapy interventions for adolescent idiopathic scoliosis

Authors: Sun Kui, Huang Hailun, Wei Yatao, Liu Yongai, Gao Heng

BACKGROUND: Adolescent idiopathic scoliosis is one of the most common spinal deformities in adolescents. As an important non-surgical treatment, exercise therapy for adolescent idiopathic scoliosis is widely used in clinical practice, yet there is a lack of systematic analysis of research trends and developments in this field. OBJECTIVE: To analyze the research hotspots, developmental dynamics, and international collaboration patterns in exercise therapy for improving adolescent idiopathic scoliosis from 1999 to 2024 using bibliometric methods, and to provide references for future research directions. METHODS: Based on the Web of Science Core Collection database, relevant literature published between January 1999 and September 2024 was retrieved, and 188 studies were ultimately included. Visualization analysis of countries/regions, institutions, authors, journals, keywords, and co-cited references was conducted using VOSviewer and CiteSpace software. RESULTS AND CONCLUSION: The number of publications in the field of exercise therapy for adolescent idiopathic scoliosis has undergone three stages, with sustained growth in recent years. China and the United States lead in publication output, while the United States has the highest average citations per paper, and Italy serves as a central hub for international collaboration. Schroth training, individualized treatment plans, and quality of life assessment are current research hotspots. Keyword evolution indicates a shift towards precise assessment and personalized intervention. Through visualization, this study identifies core author groups, high-impact journals, and key references in the field, revealing a clear path from general conservative treatment to specific, technology-integrated approaches, providing a systematic reference for scholars to quickly grasp the field's landscape and plan research directions.

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Bibliometric analysis of exercise therapy interventions for adolescent idiopathic scoliosis

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Original ResearchVol 1902, Issue 30 • pp. 100-112DOI: 10.12307/2026.21437• Jan 15, 2026

Causal relationship between plasma metabolites and osteonecrosis: a large sample analysis based on genome-wide association study database and FinnGen database

Authors: Wei Qiuyu, Yu Shaoyong, Zhou Zheyi, Wu Gang

BACKGROUND: Osteonecrosis is a disabling and refractory disease with a high prevalence rate in China, necessitating the exploration of potential biomarkers for early prevention, diagnosis, and treatment. Metabolomic studies have demonstrated correlations between human metabolites and osteonecrosis; however, the causal relationship between plasma metabolites and osteonecrosis remains unclear. OBJECTIVE: To investigate the causal association between 1,400 plasma metabolites and osteonecrosis using Mendelian randomization and provide supporting evidence. METHODS: Public data on 1,400 plasma metabolites (exposure factors) and osteonecrosis (outcome factor) were collected. The plasma metabolite data were derived from a genome-wide association study (GWAS) on blood metabolites published in Nature Genetics in January 2023, which included 1,091 blood metabolites and 309 metabolite ratios from 8,299 individuals in the Canadian Longitudinal Study on Aging (CLSA) cohort. The single-nucleotide polymorphism data for osteonecrosis were obtained from the FinnGen public database R12 dataset, comprising 475,307 samples, including 2,043 osteonecrosis cases and 473,264 controls, all of European ancestry. Mendelian randomization analyses (inverse variance weighting, MR-Egger, weighted median, simple mode, and weighted mode) were performed using Rstudio software, followed by heterogeneity tests, pleiotropy tests, and Steiger directionality tests to ensure robustness and reliability. RESULTS AND CONCLUSION: Three plasma metabolites showed significant causal associations with osteonecrosis (P < 0.05): adenosine monophosphate to valine ratio (OR=1.303, 95%CI=1.110-1.531, P=0.001, PFDR=0.07), oxidized cysteinylglycine level (OR=0.888, 95%CI=0.791-0.998, P=0.046, PFDR=0.05), and 3β,17β-androstenediol disulfate level (OR=1.121, 95%CI=1.020-1.231, P=0.018, PFDR=0.06). The adenosine monophosphate to valine ratio and 3β,17β-androstenediol disulfate level were risk factors for osteonecrosis, while oxidized cysteinylglycine level was a protective factor. These findings suggest causal relationships between three plasma metabolites and osteonecrosis, potentially serving as biomarkers for early diagnosis and targets for intervention. Although based on European population data, this study provides valuable reference for osteonecrosis research in China, and future domestic researchers may achieve early diagnosis and precise treatment by detecting and regulating metabolite levels.

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Causal relationship between plasma metabolites and osteonecrosis: a large sample analysis based on genome-wide association study database and FinnGen database

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Original ResearchVol 1902, Issue 30 • pp. 100-112DOI: 10.12307/2026.21442• Jan 15, 2026

Bibliometric analysis of research hotspots on mitochondria and spinal cord injury treatment

Authors: Wang Lei, Hu Baoyang, Fang Fang

BACKGROUND: Mitochondria are vital for axonal regeneration and apoptosis following spinal cord injury, making them an essential area of therapeutic research for this condition. OBJECTIVE: To summarize literature on mitochondria and spinal cord injury treatment, using bibliometric methods to elucidate the current research landscape, global trends, and comprehensive academic understanding in this field. METHODS: We retrieved relevant literature published between 1990 and 2024 from the Web of Science Core Collection database on topics related to mitochondria and the treatment of spinal cord injury. Visual analysis was conducted using CiteSpace 5.8 and VOS Viewer 1.6.18 software to draw knowledge maps and examine metrics such as publications, centrality, and H-index. Keyword analysis, co-cited journal analysis, co-cited document analysis, highly co-cited document analysis, and publication burst analysis were conducted to identify research hotspots and directions within the field. RESULTS AND CONCLUSION: A total of 558 publications were included in this bibliometric analysis, involving 48 countries, 3,036 authors, 713 institutions, and 252 journals. The number of publications in the field of mitochondria and spinal cord injury treatment has shown an increasing trend year by year. The United States and China have performed prominently in this field, ranking among the top globally in terms of publication output, citation frequency, core authors, and research institutions. Currently, research hotspots in this field focus on apoptosis and oxidative stress. Future research directions may center on molecular mechanisms, inflammatory responses, and neural repair. The field of mitochondria and spinal cord injury treatment holds great promise, with steady improvement in overall research level in recent years, but still faces challenges such as limited high-quality literature and significant regional disparities in research progress, which require further efforts by researchers.

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Bibliometric analysis of research hotspots on mitochondria and spinal cord injury treatment

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Original ResearchVol 1902, Issue 30 • pp. 100-112DOI: 10.12307/2026.21435• Jan 15, 2026

Zinc finger DHHC-type containing 2 emerges as a novel therapeutic target in osteoarthritis pathogenesis: genome-wide data analysis in European populations

Authors: Wei Bingqi, Zhang Xinyue, Ren Xingyue, Sun Jiahui, Chen Liu, Li Yijing, Qi Yifan, Wang Shangzeng

BACKGROUND: Studies have suggested that palmitoylation-mediated regulation offers distinct advantages in osteoarthritis. Therefore, it is essential to utilize whole-genome data to explore novel key drug-targetable tissue-constructing hubs of palmitoylation regulation in osteoarthritis from a genetic perspective. OBJECTIVE: To explore novel key drug targets involved in palmitoylation-mediated regulation of osteoarthritis pathogenesis through Mendelian randomization analysis, thereby providing valuable insights for developing targeted therapeutic strategies against osteoarthritis. METHODS: We identified 31 palmitylation-related genes from three independent studies and cross-referenced them with 15 695 druggable genes from the eQTLGen Consortium database (which is publicly available and aims to better understand diseases at the plasma proteome gene level, containing multiple druggable gene targets). This yielded 22 potential palmitoylation drug targets. Using drug-target Mendelian randomization, sensitivity analysis, and colocalization analysis, we identified novel drug targets for palmitoylation-regulated osteoarthritis (from GWAS Catalog database, established by the National Human Genome Research Institute, summarizing data from published genome-wide association studies). GeneMANIA and STRING interaction network analyses were performed to explore potential interacting proteins of the novel drug target. After further validation with osteoarthritis validation genes (also from GWAS Catalog), we determined the interacting proteins of the novel drug target. RESULTS AND CONCLUSION: (1) After matching 31 palmitoylation genes, 22 potential palmitoylation drug targets were obtained. Through Mendelian randomization, sensitivity analysis, and colocalization analysis, zinc finger DHHC-type containing 2 (ZDHHC2) was identified as a novel drug target for palmitoylation-regulated osteoarthritis. GeneMANIA and STRING analyses revealed 7 potential interacting proteins, and validation with osteoarthritis genes suggested a strong interaction between ZDHHC3 and ZDHHC2. These results indicate that ZDHHC2 is a novel key drug target in palmitoylation-regulated osteoarthritis pathogenesis, and ZDHHC3, as an interacting protein, may exert synergistic effects, facilitating future construction of efficient and safe drug prevention and treatment chains for osteoarthritis patients through palmitoylation regulation. (2) The use of international databases and European populations provides important reference for Chinese biomedical and clinical research, offering clues for osteoarthritis research in the Chinese population from a genetic perspective. This approach can also be used to screen drug gene targets in Chinese populations, target palmitoylation regulation, and promote personalized and precise medication for osteoarthritis prevention and treatment.

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Zinc finger DHHC-type containing 2 emerges as a novel therapeutic target in osteoarthritis pathogenesis: genome-wide data analysis in European populations

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Original ResearchVol 1902, Issue 30 • pp. 100-112DOI: 10.12307/2026.21436• Jan 15, 2026

Bibliometric and visualization analysis of the mechanism of osteogenic factors and neurotransmitters in the bone-brain axis

Authors: WANG Degang, MEI Junhua, WANG Junli, ZHENG Li, CHEN Guohua

BACKGROUND: In recent years, numerous studies have confirmed a close relationship between the skeletal system and the central nervous system, making the bone-brain axis a research hotspot in interdisciplinary fields; however, no studies have yet conducted a bibliometric and visualization analysis of this field. OBJECTIVE: To comprehensively analyze the research trends, hotspots, and future development directions in the bone-brain axis field utilizing bibliometric methods, providing data support and reference for subsequent studies. METHODS: A systematic literature search was conducted in the Web of Science Core Collection database to collect studies related to bone-brain axis published between 2015 and 2024. Visualization tools such as VOSviewer and CiteSpace were employed to analyze publication trends, collaboration networks, institutional contributions, and keyword co-occurrence patterns. RESULTS AND CONCLUSION: ①A total of 7,461 publications were included, showing a significant upward trend in publication volume over the past decade (2015-2024), indicating that bone-brain axis research has become an academic hotspot with increasing attention. ②The United States and China dominated the field, with the USA publishing 2,397 papers (32.1%) and China 2,307 papers (30.9%). Harvard Medical School and Zhejiang University were the most productive and central institutions. ③Professor Wang Wei was the most prolific author, focusing on the interaction between bone marrow and neuroinflammation. ④The journal Bone published the most papers (over 800), while PLOS ONE had the highest average citations per paper (45), indicating its influence. ⑤Core keywords included 'Bone Marrow', 'Stem Cells', 'Osteoporosis', and 'Neuroinflammation', reflecting fundamental research directions. Emerging frontiers included 'Extracellular Vesicles', 'Alzheimer's Disease', 'Inflammation', and 'Oxidative Stress', highlighting the importance of inflammation and neurodegenerative diseases. ⑥Future research directions include exploring the specific mechanisms of osteogenic factors and neurotransmitters in the bone-brain axis, elucidating the molecular mechanisms of inflammation, oxidative stress, and extracellular vesicles in neurodegenerative diseases and bone metabolic disorders, and promoting the translation of basic research to clinical applications.

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Bibliometric and visualization analysis of the mechanism of osteogenic factors and neurotransmitters in the bone-brain axis

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Original ResearchVol 1902, Issue 30 • pp. 100-112DOI: 10.12307/2026.21440• Jan 15, 2026

Mendelian randomization analysis identifies potential drug targets for spinal osteoarthritis

Authors: Zhao Ruikai, Wang Yu, Guo Xiaohui, Sun Zehua, Wang Xu

BACKGROUND: Spinal osteoarthritis is a common degenerative spinal disease that severely affects quality of life of patients, but its exact molecular mechanism remains unclear. OBJECTIVE: To identify plasma proteins related to spinal osteoarthritis through Mendelian randomization analysis and provide a reference for finding new potential therapeutic targets in this disease field. METHODS: Protein data were obtained from the deCODE Genetics database (A total of 35 559 Icelandic individuals were included, and genetic association information of 4 907 plasma proteins was detected, https://www.decode.com/summarydata/). Spinal osteoarthritis data were obtained from the Osteoarthritis Genetics Consortium (A total of 826 690 samples are available for free download via https://msk.hugeamp.org/downloads.html). All data are open source and comply with ethical requirements. Wald ratio or inverse variance weighting was used to assess the causal relationship between 4 907 plasma proteins and spinal osteoarthritis, with Bonferroni correction applied to the P-values. In addition, Steiger directional test was performed to exclude reverse causality; colocalization analysis to exclude linkage disequilibrium; phenotype scanning to exclude horizontal pleiotropy; and external validation to exclude chance findings. Finally, the online analysis tool Enrichr was used to screen small-molecule compounds targeting causal proteins, and molecular docking was performed for the top-ranked compounds to predict their binding modes and energies, thereby identifying the most stable and possible binding modes. RESULTS AND CONCLUSION: Among 4 907 proteins, 1 878 significant protein quantitative trait loci for 1 553 proteins were screened. After Mendelian randomization analysis, four proteins were identified to have strong causal relationships with spinal osteoarthritis: monocyte CD14, interleukin-12 subunit beta (IL12B), hepatocyte growth factor-like protein (MST1), and Semaphorin-4A (SEMA4A). IL12B was negatively correlated with spinal osteoarthritis, while the others were positively correlated. Drug prediction results showed that tesmilifene targeting CD14, montelukast targeting IL12B, naphthylamine targeting MST1, and colchicine targeting SEMA4A all exhibited good binding abilities in molecular docking, with the lowest binding energies all below -6.0 kJ/mol. Comprehensive analysis indicates that these four plasma proteins may serve as potential biomarkers or drug targets for clinical screening, prevention, and intervention of spinal osteoarthritis, and also provide theoretical basis and reference value for related research in the Chinese population.

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Mendelian randomization analysis identifies potential drug targets for spinal osteoarthritis

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Original ResearchVol 1902, Issue 30 • pp. 100-112DOI: 10.12307/2026.21423• Jan 15, 2026

Signaling pathways related to active ingredients of ginseng in the treatment of musculoskeletal degenerative diseases

Authors: Xia Tiange, Zhou Yi, Li Shaoshuo, Wang Jianwei, Shao Yang

BACKGROUND: Current therapies for musculoskeletal degenerative diseases merely alleviate symptoms with significant adverse effects. As a traditional Chinese medicine, active ingredients of ginseng exhibit protective effects on bone and muscle through multi-target regulation of signaling pathways, and breakthroughs have been made in mechanism research in recent years. OBJECTIVE: To provide a systematical review of the latest molecular mechanisms of active ingredients of ginseng (ginsenosides, polysaccharides, and peptides) in preventing and treating musculoskeletal degenerative diseases via key signaling pathways, providing a basis for targeted drug development. METHODS: A systematic search was performed in multiple databases, including PubMed, Web of Science, Embase, CNKI, Wanfang, and VIP, with the search period from inception to April 2025. Chinese search terms included "musculoskeletal diseases, osteoporosis, osteoarthritis, intervertebral disc herniation, sarcopenia, ginsenosides, ginseng polysaccharides, ginseng peptides, signaling pathways"; English search terms included "musculoskeletal degenerative diseases, osteoporosis, osteoarthritis, intervertebral disc degeneration, sarcopenia, ginsenosides, ginseng polysaccharides, ginseng peptides, signaling pathways". Finally, 75 eligible articles were included. RESULTS AND CONCLUSION: (1) Ginsenosides (e.g., Rg3, Rh4, Rc): target the karyopherin α2-nuclear factor-κB axis to inhibit osteoclast differentiation and reduce bone resorption; activate the sirtuin 1 pathway to enhance mitochondrial biogenesis and delay sarcopenia; regulate Yes-associated protein 1/transcriptional coactivator and p38 mitogen-activated protein kinase to alleviate intervertebral disc degeneration. (2) Polysaccharides: processing techniques affect immunomodulatory activity, inhibiting inflammation via the mitogen-activated protein kinase/nuclear factor-κB pathway. (3) Peptides: activate the NAD+/sirtuin 1/peroxisome proliferator-activated receptor γ coactivator 1α axis to improve mitochondrial function. These findings suggest that ginseng exerts synergistic regulation of bone metabolism balance, inhibition of cartilage degradation, and delay of muscle aging through a "multi-component, multi-target" mechanism, but challenges remain regarding low bioavailability and lack of large-scale clinical trials for translation.

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Signaling pathways related to active ingredients of ginseng in the treatment of musculoskeletal degenerative diseases

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Original ResearchVol 1902, Issue 30 • pp. 100-112DOI: 10.12307/2026.21426• Jan 15, 2026

Metabolic dysregulation in osteoarthritis: mechanisms and targeted therapeutic strategies

Authors: GUO Shanshan, MA Ding, DONG Bingchen

BACKGROUND: Osteoarthritis has traditionally been considered as a degenerative joint disorder, with the central role of metabolic dysregulation in its pathogenesis long overlooked. Recent studies reveal a strong association between metabolic syndromes, such as obesity and diabetes, and osteoarthritis progression, yet the molecular mechanisms by which metabolic dysregulation results in joint degeneration remain poorly elucidated. OBJECTIVE: To systematically review advances in the pathological mechanisms of metabolic dysregulation in osteoarthritis, integrating multi-omics evidence to decode the regulatory network of the "metabolism-joint axis," and to provide novel perspectives for the clinical prevention and treatment of metabolic dysregulation in osteoarthritis. METHODS: An online search of the China National Knowledge Infrastructure and Wanfang databases was conducted using the terms "osteoarthritis, metabolic dysregulation, adipokine, glycolysis, mitochondrial dysfunction, metabolomics, MRI" in Chinese to retrieve relevant literature. Additionally, PubMed and Web of Science were searched using the English terms "osteoarthritis, metabolic dysregulation, adipokine, glycolysis, mitochondrial dysfunction, metabolomics, MRI." After screening titles and abstracts, as well as evaluating full texts, 108 articles were finally included for review. RESULTS AND CONCLUSION: Epidemiological studies confirm that metabolic syndrome (obesity, diabetes, dyslipidemia) is positively correlated with osteoarthritis risk; each 1 kg/m2 increase in body mass index raises the risk of knee osteoarthritis by 15%, and involvement of non-weight-bearing joints supports the independent pathogenic role of metabolic factors. Imbalance of the adipokine network drives osteoarthritis progression: obesity leads to abnormal leptin/adiponectin ratio (leptin increased 3.2-fold, adiponectin decreased 40%), which accelerates cartilage degradation by activating matrix metalloproteinase 13 (increased 2.1-fold) and inhibiting tissue inhibitor of metalloproteinase 2. Intracellular metabolic reprogramming is prominent: osteoarthritic chondrocytes exhibit a triad of enhanced glycolysis, mitochondrial dysfunction, and lipid droplet deposition (free fatty acids increased 1.8-fold). A metabolic-inflammatory positive feedback loop: adipose tissue releases interleukin-1β/tumor necrosis factor-α to activate the nuclear factor-κB pathway in joints, which in turn inhibits insulin receptor signaling and exacerbates metabolic disturbance. Clinical translation: serum adiponectin combined with synovial fluid lactate can predict osteoarthritis progression; early use of AMP-activated protein kinase agonists combined with muscle training and nutritional intervention is recommended for patients with metabolic syndrome.

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Metabolic dysregulation in osteoarthritis: mechanisms and targeted therapeutic strategies

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Original ResearchVol 1902, Issue 30 • pp. 100-112DOI: 10.12307/2026.21431• Jan 15, 2026

Meta-analysis of blood flow restriction training to improve knee function and muscle strength in patients after anterior cruciate ligament reconstruction

Authors: Chen Ziang, Li Qinlong, Wu Xue, Zhou Yue

OBJECTIVE: Blood flow restriction training is a low-load training method designed to enhance muscle strength and promote muscle hypertrophy. Its characteristics align well with the rehabilitation needs following anterior cruciate ligament reconstruction. However, its actual efficacy remains unclear. Therefore, this study systematically evaluated the effectiveness of blood flow restriction training on knee joint rehabilitation in patients after anterior cruciate ligament reconstruction and compared the differences in knee rehabilitation outcomes between blood flow restriction training and traditional resistance training. METHODS: By searching EBSCO, Embase, PubMed, The Cochrane Library, Web of Science English databases, CBM, CNKI, VIP, WanFang Data Chinese databases and clinical trial center database (ClinicalTrials.gov), the randomized controlled trials of knee rehabilitation after anterior cruciate ligament reconstruction were collected. The search time was from the establishment of the database to October 31, 2024. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. The meta-analysis was performed using RevMan 5.4 software and Stata 14.0 software. RESULTS: A total of 11 studies involving 317 patients were included. Meta-analysis results showed that blood flow restriction training was superior to traditional resistance training in improving knee muscle strength [SMD=0.75, 95%CI (0.46, 1.04), P < 0.000 01], knee muscle mass [SMD=0.48, 95%CI (0.30, 0.66), P < 0.000 01], and knee function [SMD=2.69, 95%CI (1.32, 4.07), P=0.000 1]. Subgroup analysis showed that when training frequency was ≥3 times per week, knee muscle mass [SMD=0.43, 95%CI (0.23, 0.63), P < 0.000 1] was more improved than traditional resistance training. CONCLUSION: Blood flow restriction training can better improve knee muscle strength, knee muscle mass, and knee function in patients after anterior cruciate ligament reconstruction than traditional resistance training. Moreover, during the rehabilitation period, blood flow restriction training at least three times per week can better increase knee muscle mass.

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Meta-analysis of blood flow restriction training to improve knee function and muscle strength in patients after anterior cruciate ligament reconstruction

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Original ResearchVol 1902, Issue 30 • pp. 100-112DOI: 10.12307/2026.21419• Jan 15, 2026

A new strategy for preventing and treating orthopedic diseases by regulating ferroptosis through signaling pathways

Authors: HE Long, GAO Shuang, CHEN Chao, QIN Guozhong, RAN Qingsen, WANG Zhengchun, YANG Yafeng, REN Hang, QIU Yunkai, YANG Yang, LI Wei

BACKGROUND: Experiments have confirmed that ferroptosis is closely associated with a variety of orthopedic diseases. However, the specific mechanisms by which the regulation of ferroptosis leads to orthopedic diseases remain unclear. Current evidence suggests that signaling pathways may be an important approach for regulating the occurrence of ferroptosis. OBJECTIVE: To summarize the relevant signaling pathways involved in the regulation of ferroptosis in orthopedic diseases (osteoarthritis, spinal cord injury, osteoporosis, intervertebral disc degeneration, rheumatoid arthritis, osteosarcoma, steroid-induced osteonecrosis of the femoral head), to describe the key regulators of the ferroptosis pathway in orthopedic diseases through the modulation of the conduction of signaling pathways, and to conduct an in-depth study on the regulatory mechanisms of ferroptosis in orthopedic diseases and provide a theoretical basis for the prevention and treatment of such diseases. METHODS: Databases including PubMed, Elsevier, Web of Science, and CNKI were searched for relevant literatures on ferroptosis and related orthopedic diseases from the establishment of these databases up to February 2025. The search terms were "ferroptosis, osteoarthritis, osteoporosis, spinal cord injury, intervertebral disc degeneration, osteosarcomas, rheumatoid arthritis, steroid-induced osteonecrosis of the femoral head". A total of 138 articles were included for review. RESULTS AND CONCLUSION: (1) Under the regulation of multiple signaling pathways, the accumulation of intracellular iron ions, reactive oxygen species, and other substances can be induced, causing ferroptosis in osteoblasts, chondrocytes, osteosarcoma cells, etc., leading to changes in the microenvironment, thereby promoting or inhibiting the occurrence of related orthopedic diseases. (2) Studies have confirmed that signaling pathway-regulated ferroptosis is of great significance in the pathogenesis of orthopedic diseases. (3) However, the interaction mechanisms among signaling pathways, ferroptosis, and orthopedic diseases are still in the preliminary stage, and further research is needed to provide more strategies for the treatment of orthopedic diseases.

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A new strategy for preventing and treating orthopedic diseases by regulating ferroptosis through signaling pathways

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Original ResearchVol 1902, Issue 30 • pp. 100-112DOI: 10.12307/2026.21430• Jan 15, 2026

A new perspective on exercise for the prevention and treatment of type 2 diabetes mellitus: pyroptosis

Authors: Zhao Yanan, Cao Liquan, Tan Sijie

BACKGROUND: Pyroptosis, a pro-inflammatory form of programmed cell death, plays a key role in innate immunity. However, its excessive activation can induce the body's inflammatory response and the development of disease, e.g., pancreatic β-cell pyroptosis is closely associated with the pathogenesis of type 2 diabetes mellitus. Recent studies suggest that exercise may suppress β-cell pyroptosis, thereby offering potential benefits for the prevention and management of type 2 diabetes mellitus and its complications. Nevertheless, the precise mechanisms underlying the interplay among β-cell pyroptosis, type 2 diabetes mellitus, and exercise remain unclear. OBJECTIVE: To review a series of pyroptosis pathways and the molecular mechanisms of pancreatic β-cell pyroptosis and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in the pathophysiological process of type 2 diabetes mellitus, and to summarize the effects and potential mechanisms of different exercise modalities in regulating the pyroptosis of pancreatic β-cells and preventing and controlling type 2 diabetes mellitus, thereby providing theoretical and practical guidance for the prevention and control of type 2 diabetes mellitus and for the intervention of exercise. METHODS: A systematic literature search was conducted in CNKI, VIP, WanFang, Google Scholar, Web of Science, and PubMed for relevant literature published from January 2000 to April 2025. High-quality studies on exercise regulation of pyroptosis in the prevention and treatment of type 2 diabetes mellitus were screened. Based on explicit inclusion and exclusion criteria, the quality of the literature was assessed and integrated, and finally 57 articles were analyzed and summarized. RESULTS AND CONCLUSION: ① NLRP3 inflammasome-mediated pyroptosis plays an important role in the development and progression of type 2 diabetes mellitus; ② Various exercise interventions, especially aerobic exercise, can effectively improve pancreatic β-cell damage and enhance insulin sensitivity by inhibiting NLRP3-related pathways and reducing inflammatory responses; ③ Tai Chi, Yijinjing, resistance exercise, and hypoxic exercise also show certain regulatory potential. In summary, exercise intervenes in pyroptosis through multiple pathways, providing theoretical support and practical directions for new targets in the prevention and treatment of type 2 diabetes mellitus.

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A new perspective on exercise for the prevention and treatment of type 2 diabetes mellitus: pyroptosis

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Original ResearchVol 1902, Issue 30 • pp. 100-112DOI: 10.12307/2026.21433• Jan 15, 2026

Outcome measures in randomized controlled trials of vestibular peripheral vertigo: a systematic evaluation of traditional Chinese medicine treatment

Authors: HOU Mingkai, GENG Siyu, QIN Jinghan, SHEN Liya, HUANG Haoxuan, ZHAO Qianao, ZHANG Daopei, ZHANG Huailiang

Background: Vestibular peripheral vertigo is characterized by a wide range of diseases, profound impact, and difficulty in prevention and treatment, posing a significant public health issue globally. Currently, randomized controlled trials (RCTs) of traditional Chinese medicine (TCM) for vestibular peripheral vertigo are complex and diverse, lacking standardized and systematic categorization, which constrains the quality of evidence-based evidence and clinical translation value. Objective: To systematically review RCTs of TCM for vestibular peripheral vertigo, analyze clinical research characteristics and outcome measures, to optimize the development of clinical guideline indicator sets and provide reference for future clinical trial design. Methods: PubMed, Web of Science, The Cochrane Library, EMbase, CNKI, VIP, Wanfang, and China Biology Medicine disc were searched from inception to April 18, 2025, to collect RCTs of TCM for vestibular peripheral vertigo. Two researchers independently conducted literature screening, data extraction, and quality assessment. Qualitative analysis was used to summarize clinical outcome measures and related trial design elements. Results and Conclusion: A total of 166 RCTs involving 14,718 patients were included, with 119 types of outcome measures. Outcome measures were categorized into 7 domains based on functional attributes: symptoms/signs, TCM syndromes, physical and chemical examinations, safety, long-term prognosis, quality of life, and others. Currently, the design of RCTs of TCM for vestibular peripheral vertigo has not formed a unified standard, with lack of standardization in TCM syndrome types and measurement tools, and numerous methodological quality issues. Clinical outcome measures exhibit prominent heterogeneity, imbalance between endpoint and surrogate indicators, unreasonable selection, neglect of economic indicators, and incomplete safety event and long-term prognosis evaluation systems. It is recommended that future researchers improve methodological quality, rationally design outcome measures, and align with the characteristics of TCM clinical trial efficacy evaluation, to promote the standardization of clinical guidelines and core indicator sets for vestibular peripheral vertigo, and provide more scientific and effective evidence-based medicine evidence for precise prevention and treatment.

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Outcome measures in randomized controlled trials of vestibular peripheral vertigo: a systematic evaluation of traditional Chinese medicine treatment

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Original ResearchVol 1902, Issue 30 • pp. 100-112DOI: 10.12307/2026.21429• Jan 15, 2026

Role of non-coding RNAs in Alzheimer’s disease and treatment with traditional Chinese medicine

Authors: WANG Shaona, LI Ruiyang, AN Lanhua, ZHANG Jinsheng

BACKGROUND: The etiology of Alzheimer’s disease is diverse and its pathogenesis remains complex and incompletely understood. In recent years, non-coding RNAs have been demonstrated to play a key role in the regulation of amyloid-β abnormal deposition, tau hyperphosphorylation, neuroinflammation activation, mitochondrial dysfunction, and synaptic damage, offering new perspectives for elucidating mechanisms underlying diseases and development of drugs. Additionally, by regulating non-coding RNA networks, traditional Chinese medicine exhibits the advantages of multi-pathway intervention. OBJECTIVE: To review recent studies on the role of regulatory non-coding RNAs and transfer RNAs in the pathological mechanisms of Alzheimer’s disease, summarize the current status of traditional Chinese medicine monomers, compound formulas, and acupuncture in regulating different non-coding RNAs to exert anti-Alzheimer’s disease effects, and provide theoretical basis and direction reference for future optimization of clinical treatment strategies and development of novel drugs. METHODS: Using Chinese and English search terms including 'non-coding RNA, microRNA, long non-coding RNA, circular RNA, transfer RNA, Alzheimer’s disease, traditional Chinese medicine', relevant literature published from January 2015 to July 2025 was retrieved from CNKI and PubMed databases. According to inclusion and exclusion criteria, 101 articles were finally included for review. RESULTS AND CONCLUSION: (1) The occurrence and development of Alzheimer’s disease originate from a multifactorial interrelated pathological network, mainly including amyloid-β deposition, tau hyperphosphorylation, neuroinflammation activation, mitochondrial dysfunction, oxidative stress, synaptic structural and functional abnormalities, and calcium homeostasis imbalance, which can also interweave and synergistically promote disease progression. (2) Various regulatory non-coding RNAs such as microRNAs, long non-coding RNAs, circular RNAs, and transfer RNAs among housekeeping non-coding RNAs can regulate the above pathological processes at different levels, thereby affecting disease progression. (3) Many active components of traditional Chinese medicine monomers such as berberine, catalpol, Panax notoginseng saponins, ginsenoside Rg1, β-asarone, triptolide, and tanshinone IIA; traditional Chinese medicine compound formulas such as Anshen Dingzhi Formula, Tiaoxin Formula, Bushen Tiansui Formula; and acupuncture and moxibustion can upregulate or downregulate specific non-coding RNAs to intervene in multiple pathological links of Alzheimer’s disease, exert neuroprotective effects, and delay the occurrence and development of the disease.

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Role of non-coding RNAs in Alzheimer’s disease and treatment with traditional Chinese medicine

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Original ResearchVol 1902, Issue 30 • pp. 100-112DOI: 10.12307/2026.21432• Jan 15, 2026

Optimal exercise prescription for chronic low back pain in adults: a network meta-analysis

Authors: Zhao Ke, Zhang Ping, Xi Yongping, Zeng Fanzhi, Zhang Liru

OBJECTIVE: Traditional meta-analyses have confirmed that exercise intervention can effectively improve chronic low back pain, but the evidence for which specific exercise method is more effective is still insufficient. Therefore, this article used a network meta-analysis to explore the differences in the effects of different exercise elements on improving chronic low back pain in adults. METHODS: Randomized controlled trials of exercise intervention for nonspecific chronic low back pain were searched in PubMed, Web of Science, Embase, Cochrane, CNKI, WanFang, and VIP databases. The trial group received any type of exercise intervention, while the control group received non-exercise interventions such as drug therapy and physical therapy. The search period was from the database inception to March 1, 2025. Boolean operators (AND/OR) were used to combine keywords for the search. Two reviewers independently completed literature screening, data extraction, and risk of bias assessment. Stata 17.0 software was used for network meta-analysis, and the surface under the cumulative ranking curve (SUCRA) was used to rank the effects of exercise dose variables. RESULTS: A total of 40 randomized controlled trials were included. Network meta-analysis showed that core stability training, mat exercise, traditional Chinese exercises, combined exercise, and other exercises were superior to the control group in improving chronic low back pain [SMD=-0.76, 95%CI(-1.39, -0.13), P < 0.05; SMD=-1.67, 95%CI(-2.48, -0.86), P < 0.05; SMD=-2.09, 95%CI(-3.37, -0.80), P < 0.05; SMD=-1.60, 95%CI(-2.71, -0.49), P < 0.05; SMD=-1.40, 95%CI(-2.40, -0.40), P < 0.05]. Suspension training was less effective than traditional Chinese exercises and mat exercise [SMD=1.50, 95%CI(0.05, 2.95), P < 0.05; SMD=1.09, 95%CI(0.11, 2.06), P < 0.05]. Traditional Chinese exercises were superior to core stability training [SMD=-1.32, 95%CI(-2.64, -0.01), P < 0.05]. Regarding exercise duration, sessions of 15-20 min and 30-40 min were superior to control [SMD=-1.96, 95%CI(-3.55, -0.36), P < 0.05; SMD=-1.44, 95%CI(-2.12, -0.76), P < 0.05]. Regarding frequency, 3 times/week and 6-7 times/week were superior to control [SMD=-1.03, 95%CI(-1.69, -0.37), P < 0.05; SMD=-1.83, 95%CI(-2.75, -0.91), P < 0.05], and 6-7 times/week was superior to 1-2 times/week [SMD=-1.30, 95%CI(-2.61, -0.06), P < 0.05]. Regarding duration of program, 4 weeks, 12-13 weeks, and ≥16 weeks were significantly superior to control [SMD=-0.81, 95%CI(-1.50, -0.12), P < 0.05; SMD=-1.63, 95%CI(-2.82, -0.43), P < 0.05; SMD=-2.14, 95%CI(-3.36, -0.92), P < 0.05], and ≥16 weeks was superior to 6 weeks [SMD=-1.55, 95%CI(-3.03, -0.07), P < 0.05]. SUCRA results showed that traditional Chinese exercises, 15-20 min per session, 6-7 times per week, and ≥16 weeks ranked highest in their respective categories. CONCLUSION: Traditional Chinese exercises (Tai Chi, Qigong, Wuqinxi, Baduanjin), 15-20 min per session, 6-7 times per week, and ≥16 weeks may be the most effective for relieving chronic low back pain in adults. However, due to the limited number of included studies, further research is needed to provide stronger evidence.

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Optimal exercise prescription for chronic low back pain in adults: a network meta-analysis

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Original ResearchVol 1902, Issue 30 • pp. 100-112DOI: 10.12307/2026.21422• Jan 15, 2026

Blood cells and the occurrence and progression of osteoporosis: biomarkers and emerging therapeutic strategies

Authors: Hu Yingnan, Shi Wanwan, Wang Datao

BACKGROUND: Osteoporosis is a systemic bone metabolic disease characterized by deterioration of bone microstructure and increased bone fragility. Blood is not only a medium of bone metabolism, but also a major factor in the regulation of bone metabolism. The traditional theory of "osteogenesis-osteoclast" is difficult to fully explain its complex pathogenesis, but bone immunology reveals the core role of the interaction between the immune system and bone, and the effects of blood cells in osteoporosis have become a research hotspot. OBJECTIVE: To summarize the mechanism of action of blood cells in osteoporosis and evaluate its potential for related biomarkers and emerging therapeutic approaches. METHODS: A systematic literature search was conducted in CNKI, Wanfang, PubMed, and Web of Science databases using Chinese and English search terms including "blood cells, osteoporosis, biomarkers, bone metabolism, neutrophils, macrophages, bone marrow mesenchymal stem cells". A total of 65 articles were included for review. RESULTS AND CONCLUSION: Blood cells influence the occurrence and development of osteoporosis through mechanisms such as inflammation, immune response, and metabolic regulation. Blood cell-based biomarkers can serve as indicators for early screening of osteoporosis and provide effective targets for diagnosis and treatment. With advances in CRISPR-Cas9 gene editing, single-cell technology, and novel monoclonal antibody development, blood cells are expected to play an important role in the treatment of osteoporosis.

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Blood cells and the occurrence and progression of osteoporosis: biomarkers and emerging therapeutic strategies

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Original ResearchVol 1902, Issue 30 • pp. 100-112DOI: 10.12307/2026.21425• Jan 15, 2026

Systematic review of the effect of 3D-printed exoskeleton on hand function rehabilitation in stroke patients

Authors: Tang Ya, Li Long, Huang Du, Huang Zhaolu

OBJECTIVE: To systematically evaluate the clinical efficacy of different types of 3D-printed exoskeletons in hand function rehabilitation for stroke patients based on the International Classification of Functioning, Disability and Health framework. METHODS: A comprehensive search was conducted in PubMed, Cochrane Library, Web of Science, Embase, CNKI, and CBM databases for literature published between January 2015 and December 2024 on 3D-printed exoskeleton interventions for post-stroke hand function rehabilitation. Two researchers independently screened studies, extracted data, and assessed methodological quality following the PRISMA guidelines for systematic reviews. RESULTS: A total of 13 studies involving 62 stroke patients from the United States, China, the Netherlands, Italy, Singapore, and Turkey were finally included. Based on the Brunnstrom stages, exoskeletons were categorized into four types: assistive (Stage I), corrective (Stages II–III), training-oriented (Stages IV–VI), and compensatory (Stages IV–VI). Interventions were delivered via institution-based, home-based, or combined institution-home rehabilitation, with session durations ranging from 15 to 90 minutes, frequencies of 3 to 7 sessions per week, and durations of 5 to 8 weeks. Results showed that assistive exoskeletons improved fine hand use and self-care; corrective exoskeletons improved joint mobility, muscle tone, grip strength, and fine hand use; training-oriented exoskeletons improved joint mobility, upper limb muscle strength, and self-care; compensatory exoskeletons enhanced fine hand use and hand and arm use. CONCLUSION: Based on the ICF framework, evidence indicates that 3D-printed exoskeletons improve hand function, activity, and participation in stroke patients. It is recommended to select matching exoskeleton types according to Brunnstrom stages and develop individualized intervention plans to achieve optimal rehabilitation outcomes.

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Systematic review of the effect of 3D-printed exoskeleton on hand function rehabilitation in stroke patients

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