In recent years, the rapid development of digital intelligence has provided a new path for rare disease data sharing and injected new power into the progress of research of rare diseases. This research is aimed at summarizing and consolidating relevant literatures on data sharing driven by digital intelligence (DI) in China and abroad, and constructing a local theoretical framework of DI-driven data sharing for rare diseases based on the status of rare diseases in China. Searching PubMed, EMbase, Cochrane, CNKI, Wanfang, and VIP database, we obtain a total of 214 representative literatures. Through literature review, we find that DI technologies have played important roles in different aspects of rare disease data sharing. China, the United States, and Europe have formed their own DI-driven data sharing systems for rare disease. From the theory of " Information Commons", we analyze the gap between China′s current situation and the goal of a " Rare Disease Data Commons". Based on the analysis, we put forward the idea of framework of " DI-STARS". China should develop the Data Sharing system making DI as the core of the system. Meanwhile, China should strengthen the data standardization system, create an innovation-encouraging environment, and build a bridge between different platforms. Using the DI-STARS theory, China will be able to build the " Rare Disease Data Commons" so that the diagnosis and treatment of rare diseases will be enhanced in China to meet the patients′ needs.

Dendrobium officinale(DO) is a traditional Chinese medicinal and edible plant, while it is critically endangered worldwide. This article, primarily based on the original research findings of the author's team and available articles, provides a comprehensive overview of the factors contributing to the endangerment of DO and the key technologies for the conservation, efficient cultivation, and value-added utilization of this plant. The scarcity of wild populations, low seed-setting rates, lack of endosperm in seeds, and the need for symbiosis with endophytic fungi for seed germination under natural conditions are identified as the primary causes for the rarity and endangerment of DO. Artificial seed production and tissue culture are highlighted as key technologies for alleviating the endangered status. The physiological and ecological mechanisms underlying the adaptation of DO to epiphytic growth are explored, and it is proposed that breaking the coupling of high temperature and high humidity is essential for preventing southern blight, a devastating affliction of DO. The roles of endophytic fungi in promoting the growth, improving the quality, and enhancing the stress resistance of DO are discussed. Furthermore, the integration of variety breeding, environment selection, and co-culture with endophytic fungi is emphasized as a crucial approach for efficient cultivation. The value-added applications of DO in pharmaceuticals, health foods, food products, and daily chemicals-particularly in the food and daily chemical industries-are presented as key drivers for a 10-billion-RMB-level industry. This systematic review offers valuable insights for the further development, utilization, and industrialization of DO resources, as well as for the broader application of conservation strategies for other rare and endangered plant species.
Dendrobium/microbiology* ; Endangered Species ; Seeds/microbiology* ; Fungi/physiology*

The primary cilium is a microtubule-based organelle that projects from the cell surface. It is present in cells from single-celled eukaryotes to vertebrates, including humans. Recent studies have found that primary cilia are also widely distributed in multiple organs and tissues of the reproductive system, where they influence reproductive function by directly participating in or indirectly regulating related signaling pathways, thereby affecting fertility. Primary cilia participate in the regulation of oocyte meiosis and development. They also influence sperm maturation by regulating the homeostatic microenvironment required for spermiogenesis. By mediating Hedgehog (Hh) and Wnt signaling pathways, primary cilia regulate endometrial receptivity and decidual response, thereby influencing the embryo implantation rate. Furthermore, primary cilia control the migration, invasion, differentiation, and vascular remodeling of human chorionic villi mesenchymal stromal cells and trophoblasts. Structural or functional impairment of primary cilia may disrupt placental vascular remodeling, leading to placental hypoplasia, potentially through the downregulation of downstream target genes of the Hh signaling pathway. Moreover, primary cilia may be involved in ovarian aging, ovulation, and endocrine function. This article reviews the research progress on the relationship between primary cilia and fertility, explores the potential mechanisms underlying roles of primary cilia in gamete development, endometrial receptivity, decidualization, placental development, and ovarian reproductive endocrine function, and aims to provide new insights for fertility preservation and the prevention and treatment of human reproductive disorders.

Osteosarcoma (OS), chondrosarcoma (CS), and Ewing sarcoma (ES) represent primary malignant bone tumors and pose significant challenges in oncology research and clinical management. Conventional research methods, such as two-dimensional (2D) cultured tumor cells and animal models, have limitations in recapitulating the complex tumor microenvironment (TME) and often fail to translate into effective clinical treatments. The advancement of three-dimensional (3D) culture technology has revolutionized the field by enabling the development of in vitro constructed bone tumor models that closely mimic the in vivo TME. These models provide powerful tools for investigating tumor biology, assessing therapeutic responses, and advancing personalized medicine. This comprehensive review summarizes the recent advancements in research on 3D tumor models constructed in vitro for OS, CS, and ES. We discuss the various techniques employed in model construction, their applications, and the challenges and future directions in this field. The integration of advanced technologies and the incorporation of additional cell types hold promise for the development of more sophisticated and physiologically relevant models. As research in this field continues to evolve, we anticipate that these models will play an increasingly crucial role in unraveling the complexities of malignant bone tumors and accelerating the development of novel therapeutic strategies.
Bone Neoplasms/pathology* ; Humans ; Osteosarcoma/pathology* ; Tumor Microenvironment ; Sarcoma, Ewing/pathology* ; Chondrosarcoma/pathology* ; Animals ; Cell Culture Techniques/methods* ; Cell Culture Techniques, Three Dimensional/methods* ; Cell Line, Tumor

[Objective]To explore the alleviating effect of Yunpi Yishen Tongdu Decoction on spinal lesion and immune inflammation of ankylosing spondylitis(AS)model mice,and to provide a scientific basis for its clinical application.[Methods]A total of 42 female BALB/c mice were randomly divided into blank group,model group,western medicine group,low,medium and high dose Yunpi Yishen Tongdu Decoction groups.Except for blank group,the remaining 5 groups were injected with proteoglycans in the abdominal cavity to construct AS model.After modeling,the mice in blank group and model group were given 0.9％sodium chloride solution,the mice in western medicine group were given 3.57 mg·mL-1 celecoxib solution,and the mice in the low,medium,and high dose Yunpi Yishen Tongdu Decoction were given 0.9,1.8 and 3.6 mg·mL-1 of Yunpi Yishen Tongdu Decoction for 4 weeks,respectively.After gavage,the behavioral changes,serum inflammation cytokines,spinal lesions,and expression of receptor activator of nuclear factor-κB ligand(RANKL),receptor activator of nuclear factor-κB(RANK),and osteoclastogenesis inhibitory factor(OPG)in the spine were measured.[Results]Compared with blank group,model group had significantly increased total time in tail immobility,serum interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)level,spinal pathological score,RANKL and RANK expression(P＜0.01,P＜0.05),while the vertebral bone mineral density and OPG expression of the spine were significantly decreased(P＜0.01).After treatment with the Yunpi Yishen Tongdu Decoction,the latency time in tail immobility in AS mice was significantly reduced,along with decreased serum levels of IL-6 and TNF-α and a notable reduction in spinal pathological scores(P＜0.01,P＜0.05).Additionally,the treatment downregulated RANKL and RANK expression,upregulated OPG expression(P＜0.01,P＜0.05).[Conclusion]Yunpi Yishen Tongdu Decoction alleviates the bone destruction of AS by affecting the RANKL/RANK/OPG pathway.

OBJECTIVE: Pneumoconiosis, a lung disease caused by irreversible fibrosis, represents a significant public health burden. This study investigates the causal relationships between gut microbiota, gene methylation, gene expression, protein levels, and pneumoconiosis using a multi-omics approach and Mendelian randomization (MR). METHODS: We analyzed gut microbiota data from MiBioGen and Esteban et al. to assess their potential causal effects on pneumoconiosis subtypes (asbestosis, silicosis, and inorganic pneumoconiosis) using conventional and summary-data-based MR (SMR). Gene methylation and expression data from Genotype-Tissue Expression and eQTLGen, along with protein level data from deCODE and UK Biobank Pharma Proteomics Project, were examined in relation to pneumoconiosis data from FinnGen. To validate our findings, we assessed self-measured gut flora from a pneumoconiosis cohort and performed fine mapping, drug prediction, molecular docking, and Phenome-Wide Association Studies to explore relevant phenotypes of key genes. RESULTS: Three core gut microorganisms were identified: Romboutsia ( OR = 0.249) as a protective factor against silicosis, Pasteurellaceae ( OR = 3.207) and Haemophilus parainfluenzae ( OR = 2.343) as risk factors for inorganic pneumoconiosis. Additionally, mapping and quantitative trait loci analyses revealed that the genes VIM, STX8, and MIF were significantly associated with pneumoconiosis risk. CONCLUSIONS This multi-omics study highlights the associations between gut microbiota and key genes ( VIM, STX8, MIF) with pneumoconiosis, offering insights into potential therapeutic targets and personalized treatment strategies.
Humans ; Male ; East Asian People/genetics* ; Europe ; Gastrointestinal Microbiome ; Lung ; Macrophage Migration-Inhibitory Factors/metabolism* ; Mendelian Randomization Analysis ; Multiomics ; Pneumoconiosis/microbiology* ; Intramolecular Oxidoreductases

Approximately 70% epilepsy may be associated with genetic etiology. To date, more than 2 900 genes related to epilepsy have been reported, and genotype-phenotype association in epilepsy has received increasing attention. Explaining how mutations in the same gene can lead to different diseases or phenotypes remains challenging. Sub-molecular mechanisms, including functional structural domains, amino acid substitutions, isoforms, and monoallelic/biallelic mutations, provide new perspectives for deciphering genotype-phenotype association in epilepsy. This review summarizes the role of sub-molecular mechanisms in genotype-phenotype association in epilepsy, to provide new strategies for clinical diagnosis and precise treatment of epilepsy.

[Objective]To explore the alleviating effect of Yunpi Yishen Tongdu Decoction on spinal lesion and immune inflammation of ankylosing spondylitis(AS)model mice,and to provide a scientific basis for its clinical application.[Methods]A total of 42 female BALB/c mice were randomly divided into blank group,model group,western medicine group,low,medium and high dose Yunpi Yishen Tongdu Decoction groups.Except for blank group,the remaining 5 groups were injected with proteoglycans in the abdominal cavity to construct AS model.After modeling,the mice in blank group and model group were given 0.9％sodium chloride solution,the mice in western medicine group were given 3.57 mg·mL-1 celecoxib solution,and the mice in the low,medium,and high dose Yunpi Yishen Tongdu Decoction were given 0.9,1.8 and 3.6 mg·mL-1 of Yunpi Yishen Tongdu Decoction for 4 weeks,respectively.After gavage,the behavioral changes,serum inflammation cytokines,spinal lesions,and expression of receptor activator of nuclear factor-κB ligand(RANKL),receptor activator of nuclear factor-κB(RANK),and osteoclastogenesis inhibitory factor(OPG)in the spine were measured.[Results]Compared with blank group,model group had significantly increased total time in tail immobility,serum interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)level,spinal pathological score,RANKL and RANK expression(P＜0.01,P＜0.05),while the vertebral bone mineral density and OPG expression of the spine were significantly decreased(P＜0.01).After treatment with the Yunpi Yishen Tongdu Decoction,the latency time in tail immobility in AS mice was significantly reduced,along with decreased serum levels of IL-6 and TNF-α and a notable reduction in spinal pathological scores(P＜0.01,P＜0.05).Additionally,the treatment downregulated RANKL and RANK expression,upregulated OPG expression(P＜0.01,P＜0.05).[Conclusion]Yunpi Yishen Tongdu Decoction alleviates the bone destruction of AS by affecting the RANKL/RANK/OPG pathway.

Approximately 70% epilepsy may be associated with genetic etiology. To date, more than 2 900 genes related to epilepsy have been reported, and genotype-phenotype association in epilepsy has received increasing attention. Explaining how mutations in the same gene can lead to different diseases or phenotypes remains challenging. Sub-molecular mechanisms, including functional structural domains, amino acid substitutions, isoforms, and monoallelic/biallelic mutations, provide new perspectives for deciphering genotype-phenotype association in epilepsy. This review summarizes the role of sub-molecular mechanisms in genotype-phenotype association in epilepsy, to provide new strategies for clinical diagnosis and precise treatment of epilepsy.

OBJECTIVES: To investigate the expression of cartilage acidic protein 1 (CRTAC1) in gastric cancer (GC) and its effect on biological behaviors and immune cell infiltration of GC. METHODS: Transcriptomic, GO and KEGG analyses were conducted to investigate the association of CRTAC1 expression with prognosis of GC patients and its involvement in cell function and signaling pathways. ESTIMATE algorithm was used to analyze the effect of CRTAC1 expression on the tumor microenvironment and the tumor mutation load. In two GC cell clines (HGC-27 and MKN-74), CCK8, EdU and clone formation assays, flow cytometry, and Hoechst staining were used to examine the effects of CRTAC1 knockdown on cell proliferation, cell cycle changes and apoptosis. Wound healing assay, Transwell assay, and Western blotting were performed to analyze the effect of CRTAC1 knockdown on GC cell migration and the underlying mechanism. RESULTS: Bioinformatics analysis showed significantly higher expression of CRTAC1 in GC tissues than in adjacent tissues (P<0.05). Age and tumor stage were both prognostic risk factors in GC patients with high CRTAC1 expression (P<0.001). Analysis using ESTIMATE algorithm showed that CRTAC1 expression increased immune cell infiltration and decreased tumor mutational load in GC (P<0.001). In HGC-27 and MKN-74 cells, CRTAC1 knockdown significantly inhibited cell proliferation and migration and promoted cell apoptosis. Western blotting demonstrated that CRTAC1 knockdown significantly increased E-cadherin expression and reduced the expression levels of vimentin, p-PI3K, AKT2, p-AKT and p-mTOR in GC cells. CONCLUSIONS High expression of CRTAC1 in GC tissues affects immunotherapeutic efficacy and prognosis of the patients, possibly by promoting epithelial-mesenchymal transition via modulating tumor mutational load, tumor microenvironment, and the PI3K/AKT signaling pathway.
Stomach Neoplasms/metabolism* ; Humans ; Cell Proliferation ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction ; Cell Movement ; Cell Line, Tumor ; Prognosis ; Apoptosis ; Tumor Microenvironment ; Female ; Male ; Epithelial-Mesenchymal Transition/genetics*