OBJECTIVES: Osteoarthritis (OA) and sarcopenia are significant health concerns in the elderly, substantially impacting their daily activities and quality of life. However, the relationship between them remains poorly understood. This study aims to uncover common biomarkers and pathways associated with both OA and sarcopenia. METHODS: Gene expression profiles related to OA and sarcopenia were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between disease and control groups were identified using R software. Common DEGs were extracted via Venn diagram analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to identify biological processes and pathways associated with shared DEGs. Protein-protein interaction (PPI) networks were constructed, and candidate hub genes were ranked using the maximal clique centrality (MCC) algorithm. Further validation of hub gene expression was performed using 2 independent datasets. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of key genes for OA and sarcopenia. Mouse models of OA and sarcopenia were established. Hematoxylin-eosin and Safranin O/Fast Green staining were used to validate the OA model. The sarcopenia model was validated via rotarod testing and quadriceps muscle mass measurement. Real-time reverse transcription PCR (real-time RT-PCR) was employed to assess the mRNA expression levels of candidate key genes in both models. Gene set enrichment analysis (GSEA) was conducted to identify pathways associated with the selected shared key genes in both diseases. RESULTS: A total of 89 common DEGs were identified in the gene expression profiles of OA and sarcopenia, including 76 upregulated and 13 downregulated genes. These 89 DEGs were significantly enriched in protein digestion and absorption, the PI3K-Akt signaling pathway, and extracellular matrix-receptor interaction. PPI network analysis and MCC algorithm analysis of the 89 common DEGs identified the top 17 candidate hub genes. Based on the differential expression analysis of these 17 candidate hub genes in the validation datasets, AEBP1 and COL8A2 were ultimately selected as the common key genes for both diseases, both of which showed a significant upregulation trend in the disease groups (all P<0.05). The value of area under the curve (AUC) for AEBP1 and COL8A2 in the OA and sarcopenia datasets were all greater than 0.7, indicating that both genes have potential value in predicting OA and sarcopenia. Real-time RT-PCR results showed that the mRNA expression levels of AEBP1 and COL8A2 were significantly upregulated in the disease groups (all P<0.05), consistent with the results observed in the bioinformatics analysis. GSEA revealed that AEBP1 and COL8A2 were closely related to extracellular matrix-receptor interaction, ribosome, and oxidative phosphorylation in OA and sarcopenia. CONCLUSIONS AEBP1 and COL8A2 have the potential to serve as common biomarkers for OA and sarcopenia. The extracellular matrix-receptor interaction pathway may represent a potential target for the prevention and treatment of both OA and sarcopenia.
Sarcopenia/genetics* ; Osteoarthritis/genetics* ; Computational Biology/methods* ; Humans ; Protein Interaction Maps/genetics* ; Animals ; Mice ; Gene Expression Profiling ; Gene Ontology ; Transcriptome ; Male ; Signal Transduction/genetics* ; Gene Regulatory Networks

OBJECTIVES: Osteoarthritis (OA) is one of the most common chronic degenerative diseases, with chondrocyte apoptosis and extracellular matrix (ECM) degradation as the major pathological changes. The mechanical stimulation can attenuate chondrocyte apoptosis and promote ECM synthesis, but the underlying molecular mechanisms remain unclear. This study aims to investigate the role of primary cilia (PC) in mediating the effects of mechanical stimulation on OA progression. METHODS: In vivo, conditional knockout mice lacking intraflagellar transport 88 (IFT88^flox/flox IFT88 knockout; i.e., primary cilia-deficient mice) were generated, with wild-type mice as controls. OA models were established via anterior cruciate ligament transection combined with destabilization of the medial meniscus, followed by treadmill exercise intervention. OA progression was evaluated by hematoxylin-eosin staining, safranin O-fast green staining, and immunohistochemistry; apoptosis was assessed by TUNEL staining; and limb function by rotarod testing. In vitro, primary articular chondrocytes were isolated from mice and transfected with lentiviral vectors to suppress IFT88 expression, thereby constructing a primary cilia-deficient cell model. Interleukin-1β (IL-1β) was used to induce an inflammatory environment, while cyclic tensile strain (CTS) was applied via a cell stretcher to mimic mechanical loading on chondrocytes. Immunofluorescence and Western blotting were used to detect the protein expression levels of type II collagen α1 chain (COL2A1), primary cilia, IFT88, and caspase-12; reverse transcription polymerase chain reaction was performed to assess COL2A1 mRNA levels; and flow cytometry was used to evaluate apoptosis. RESULTS: In vivo, treadmill exercise significantly reduced Osteoarthritis Research Society International (OARSI) scores and apoptotic cell rates, and improved balance ability in wild-type OA mice, whereas IFT88-deficient OA mice showed no significant improvement. In vitro, CTS inhibited IL-1β-induced ECM degradation and apoptosis in primary chondrocytes; however, this protective effect was abolished in cells with suppressed primary cilia expression. CONCLUSIONS Mechanical stimulation delays OA progression by mediating signal transduction through primary cilia, thereby inhibiting cartilage degeneration and chondrocyte apoptosis.
Animals ; Chondrocytes/cytology* ; Apoptosis/physiology* ; Mice ; Cilia/metabolism* ; Osteoarthritis/pathology* ; Extracellular Matrix/metabolism* ; Mice, Knockout ; Disease Progression ; Interleukin-1beta ; Male ; Cells, Cultured

Successful cloning through somatic cell nuclear transfer (SCNT) faces significant challenges due to epigenetic obstacles. Recent studies have highlighted the roles of H3K4me3 and H3K27me3 as potential contributors to these obstacles. However, the underlying mechanisms remain largely unclear. In this study, we generated genome-wide maps of H3K4me3 and H3K27me3 in mouse pre-implantation NT embryos. Our analysis revealed that aberrantly over-represented broad H3K4me3 domain and H3K27me3 signal lead to increased bivalent marks at gene promoters in NT embryos compared with naturally fertilized (NF) embryos at the 2-cell stage, which may link to relatively low levels of H3K36me3 in NT 2-cell embryos. Notably, the overexpression of Setd2, a H3K36me3 methyltransferase, successfully restored multiple epigenetic marks, including H3K36me3, H3K4me3, and H3K27me3. In addition, it reinstated the expression levels of ZGA-related genes by reestablishing H3K36me3 at gene body regions, which excluded H3K27me3 from bivalent promoters, ultimately improving cloning efficiency. These findings highlight the excessive bivalent state at gene promoters as a potent barrier and emphasize the removal of these barriers as a promising approach for achieving higher cloning efficiency.
Animals ; Mice ; Histone-Lysine N-Methyltransferase/biosynthesis* ; Histones/genetics* ; Nuclear Transfer Techniques ; Female ; Gene Expression Regulation, Developmental ; Promoter Regions, Genetic ; Epigenesis, Genetic ; Embryo, Mammalian/metabolism*

To summarize Professor WANG Xixing's clinical experience in treating advanced breast cancer with anxiety and depression from the perspective of shaoyang pivot. It is believed that the core pathogenesis of advanced breast cancer with anxiety and depression lies in the dysfunction of shaoyang pivot （referring to the imbalanced regulatory function of the shaoyang meridian system that governs the transportation and transformation of qi， blood， and body fluids）. This dysfunction can lead to abnormal circulation of qi， blood， and body fluids， as well as the intermingling of phlegm and blood stasis， which further promotes the spread and diffusion of cancer toxin. Meanwhile， it disturbs mental activity， resulting in a condition characterized by stagnation of cancer toxin and concurrent disorders of both the physical body and the spirit. Based on this pathogenesis， the basic therapeutic principles of harmonizing shaoyang， regulating the pivot to calm the spirit， and dissipating masses and resolving toxins are proposed. Clinically， the disease is classified into three syndromes for differentiation and treatment. For shaoyang pivot dysfunction syndrome， treatment should use self-prescribed Chaiqin Hengshu Ningxin Decoction （柴芩衡枢宁神汤）； for sanjiao pivot dysfunction syndrome， treatment should prescribe Chaigui Tongshu Dashen Decoction （柴归通枢达神饮）； for gallbladder function disorder syndrome， treatment should apply Wendan Qishu Shoushen Decoction （温胆启枢守神汤）. Throughout the treatment process， the concept of "simultaneous treatment of cancer and depression" is implemented to smooth the shaoyang pivot， block the vicious cycle where cancer toxin and emotional abnormalities mutually reinforce each other.

Objective:On the basis of summarizing the previous studies on the access and pricing strategies of multi-indication drugs,based on the actual situation in China,it develops the access and pricing strategies of multi-indication drugs applicable to the adjustment mechanism of China's health insurance catalog and carry out feasibility analysis,with a view to providing methodological support for the national health insurance department in the adjustment of the health insurance catalog in the future.Methods:First,through literature review and expert survey,it sorts out the medical insurance access and pricing strategies for multi-indication drugs that may be applicable in China.Secondly,a feasibility evaluation framework for National Drug Insurance List(NRDL)access and pricing strategies for multi-indication drugs is constructed through literature review,and various stakeholders in the NRDL process are invited to conduct feasibility scores based on the questionnaire.In addition,9 pathways are identified through expert research,and various stakeholders in NRDL process are invited to conduct path analysis based on questionnaires.Finally,relevant recommendations are formed based on the research results.Results:According to the results of the feasibility evaluation the direct access is less feasi-ble,while negotiated access and simplified negotiated access are comparable;pricing by weighted average was less feasible,pricing by primary indication and pricing by minimum value are comparable.The results of the pathway analysis show that differences in health insurance access and pricing strategies for selecting drugs with multiple indications under different pathways.Conclusion:It is needed to refine the medical insurance access and price calculation methods for drugs with multiple indications;improve the database construction to support refined calculation of medical insurance;and actively explore the innovative payment methods for medical insurance with multiple indications.

Objective:To explore the construction of a medical Artificial Intelligence(AI)technology assessment system suitable for the national conditions in China.Methods:Summarize the domestic and international traditional health technology assessment system,and analyze the distinctive characteristics and novel risk factors of medical AI technology.Results:The existing evaluation indexes of technical characteristics are most likely to assess AI technology based on the sub-evaluation indexes of reliability,but the evaluation focus of reliability cannot be assessed for algorithms,big data,arithmetic power and the existence of risk factors,and the existing system of health technology assessment needs to be further improved.Conclusion:Traditional health technology assessment system is challenging to apply to the evaluation of medical AI technology.It is recommended to use the traditional health technology assessment framework as a foundational structure,incorporate evaluation indicators related to the characteristics of medical AI technology,and refer to evaluation indicators and methods from relevant fields to adjust and refine the medical AI technology assessment system.

Objective:To explore the construction of a medical Artificial Intelligence(AI)technology assessment system suitable for the national conditions in China.Methods:Summarize the domestic and international traditional health technology assessment system,and analyze the distinctive characteristics and novel risk factors of medical AI technology.Results:The existing evaluation indexes of technical characteristics are most likely to assess AI technology based on the sub-evaluation indexes of reliability,but the evaluation focus of reliability cannot be assessed for algorithms,big data,arithmetic power and the existence of risk factors,and the existing system of health technology assessment needs to be further improved.Conclusion:Traditional health technology assessment system is challenging to apply to the evaluation of medical AI technology.It is recommended to use the traditional health technology assessment framework as a foundational structure,incorporate evaluation indicators related to the characteristics of medical AI technology,and refer to evaluation indicators and methods from relevant fields to adjust and refine the medical AI technology assessment system.

Objective:To explore the construction of a medical Artificial Intelligence(AI)technology assessment system suitable for the national conditions in China.Methods:Summarize the domestic and international traditional health technology assessment system,and analyze the distinctive characteristics and novel risk factors of medical AI technology.Results:The existing evaluation indexes of technical characteristics are most likely to assess AI technology based on the sub-evaluation indexes of reliability,but the evaluation focus of reliability cannot be assessed for algorithms,big data,arithmetic power and the existence of risk factors,and the existing system of health technology assessment needs to be further improved.Conclusion:Traditional health technology assessment system is challenging to apply to the evaluation of medical AI technology.It is recommended to use the traditional health technology assessment framework as a foundational structure,incorporate evaluation indicators related to the characteristics of medical AI technology,and refer to evaluation indicators and methods from relevant fields to adjust and refine the medical AI technology assessment system.

Objective:To explore the construction of a medical Artificial Intelligence(AI)technology assessment system suitable for the national conditions in China.Methods:Summarize the domestic and international traditional health technology assessment system,and analyze the distinctive characteristics and novel risk factors of medical AI technology.Results:The existing evaluation indexes of technical characteristics are most likely to assess AI technology based on the sub-evaluation indexes of reliability,but the evaluation focus of reliability cannot be assessed for algorithms,big data,arithmetic power and the existence of risk factors,and the existing system of health technology assessment needs to be further improved.Conclusion:Traditional health technology assessment system is challenging to apply to the evaluation of medical AI technology.It is recommended to use the traditional health technology assessment framework as a foundational structure,incorporate evaluation indicators related to the characteristics of medical AI technology,and refer to evaluation indicators and methods from relevant fields to adjust and refine the medical AI technology assessment system.

Objective To evaluate the applicability of a modified U-shaped forearm flap for the repair of small-and medium-sized defects in the oral and maxillary areas to provide a reference for clinicians.Methods This study was re-viewed and approved by the Ethics Committee,and informed consent was obtained from the patients.Ten patients with small-and medium-sized defects in the oral and maxillary areas underwent surgical repair using modified U-shaped fore-arm flaps.There were 8 males and 2 females aged 43-72 years.The donor site was apposed primarily after harvesting the modified U-shaped forearm skin flap.The flaps ranged from 6 cm × 4 cm to 8 cm × 5 cm in size.Six months after the operation,hand movements(finger extension,fist clenching,wrist rotation upward and wrist rotation downward),the forearm donor site,hand sensations and the satisfaction score for the postoperative quality of the scar at the donor site were evaluated(0 to 10;0:very unattractive,10:very satisfactory).Results A total of 10 patients with modified U-shaped forearm flaps survived.One patient developed venous crisis 24 hours after surgery and survived after surgical ex-ploration.Delayed healing occurred at the donor site of the forearm in 1 patient,and the wounds at the donor site of the forearm in the other patients all healed in the first stage.One patient presented with dysesthesia in the hand 2 weeks af-ter surgery and recovered within 3 months.Six months after surgery,all patients had no limited hand movement and no paresthesia at the forearm donor site or hand.The patients were basically satisfied with the appearance of the donor site,and the average satisfaction score of the subjective questionnaire was 8.4 points.Conclusion Modified U-shaped fore-arm flaps can directly close forearm donor site wounds,which avoids surgical trauma to the secondary donor site and sig-nificantly reduces related complications.Modified U-shaped forearm flaps provide an alternative to conventional forearm flaps for the repair of small-and medium-sized defects in the oral and maxillary areas.