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 To investigate the protective effect of dapagliflozin on kidney and the expression of AMP-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)signaling pathway in diabetic nephropathy(DN)rats.Methods A total of 40 SPF Wistar male rats were randomly divided into normal group,model group,low-dose group and high-dose group,with 10 rats in each group.After the DN model was successfully prepared,the rats in normal group were given normal diet + normal saline by gavage,the rats in model group was given high sugar and high fat feed + normal saline by gavage,the rats in low-dose group was given high sugar and high fat feed+1mg/(kg·d)of dapagliflozin by gavage,the rats in high-dose group was given high sugar and high fat feed+10mg/(kg·d)of dapagliflozin by gavage.Rats in each group were continuously gavaged for 12 weeks.Renal function indexes,renal pathological changes,p-AMPK and p-mTOR protein expression,collagen type Ⅰ(COL Ⅰ),collagen type Ⅳ(COL Ⅳ)and fibronectin(FN)of all groups were compared.Results Blood urea nitrogen(BUN),serum creatinine(SCr),24h urinary protein quantity,p-mTOR protein expression,COL Ⅰ,COL Ⅳ and FN levels of rats in model group,low-dose group and high-dose group were significantly higher than those in normal group,and p-AMPK protein expression was significantly lower than that of normal group(P<0.05).BUN,SCr,24h urinary protein quantity,p-mTOR protein expression,COL Ⅰ,COL Ⅳ and FN levels of rats in low-dose group and high-dose group were significantly lower than those in model group,while p-AMPK protein expression was significantly higher than that in model group(P<0.05).BUN,SCr,24h urinary protein quantity,p-mTOR protein expression,COL Ⅰ,COL Ⅳ and FN levels in high-dose group were significantly lower than those in low-dose group,and p-AMPK protein expression was significantly higher than that in low-dose group(P<0.05).Conclusion Dapagliflozin has a good kidney protection effect on DN rats,and its mechanism may be related to the regulation of AMPK/mTOR signaling pathway.

Objective: To explore the effects of different concentrations of glucose solution on the survival of Aedes albopictus and Culex pipiens pallens larvae, the attraction to mosquitoes and egg-laying behaviors, so as to provide the reference for developing mosquito control technology based on sugar bait. Methods: White porcelain bowls were filled with 100 mL of 3%, 5%, 8%, 10% and 15% glucose solutions. Ten of fourth instar larvae of Aedes albopictus or Culex pipiens pallens were added to each bowl, and the survival of larvae was recorded after 2, 4, 6, 24, 48 and 72 hours. Egg-laying cups containing 5%, 8% and 15% glucose solution were put in mosquito cages containing fully blooded female mosquitoes of Aedes albopictus and Culex pipiens pallens (50 mosquitoes each), and the total number of eggs laid in 72 hours was observed. The analogous site room was filled with fully blooded and starved female mosquitoes of Aedes albopictus and Culex pipiens pallens (100 mosquitoes each), and simple mosquito control buckets containing 5% and 8% glucose solution and black sticky insect plates. The number of mosquitoes and eggs was observed after 6 days. All the above experiments were repeated 3 times using dechlorinated water as the control. Results: The 72 hour corrected mortality rates of Aedes albopictus and Culex pipiens pallens larvae gradually increased with the increase of glucose concentration. The glucose solution with 5% and higher concentrations was not suitable for mosquito larvae to survive. The attraction of egg-laying behaviors to Aedes albopictus and Culex pipiens pallens gradually decreased with the increase of glucose concentration. The effects were similar between 5% and 8% glucose solution, with the averages of 686.67 and 682.33 eggs for Aedes albopictus, and 3.00 and 2.33 egg rafts for Culex pipiens pallens. In analogous site room, there were 93.33, 105.00 and 130.33 adult mosquitoes captured on average in the control group, 5% and 8% glucose solution groups, respectively, with 8% glucose solution group more attractive to adult mosquitoes than the control group (F=3.283, P=0.030); there were 70.33, 55.33 and 63.00 Aedes albopictus eggs (eggs counts+larvae counts) on average, respectively, with statistically significant differences among the three groups (H=6.761, P=0.034). Conclusion Glucose solution with concentration of 5% or higher can effectively inhibit the survival of Aedes albopictus and Culex pipiens pallens larvae, and attractive to adult mosquitoes and egg-laying behavoirs.

Background Exposure to per- and polyfluoroalkyl substances (PFAS) is associated with various cancers, and recent studies suggest it may also increase the risk of retinoblastoma (RB) in newborns. However, the pathogenic mechanisms remain unclear. Objective By constructing an adverse outcome pathway (AOP) framework based on public databases to elucidate the potential mechanisms linking PFAS and RB. Methods Chemical-gene interactions and disease-gene interactions from the Comparative Toxicogenomics Database were retracted to identify key toxicological disruption pathways using Kyoto Encyclopedia of Genes and Genomes (KEGG) and a priori knowledge. The Pathview package in R was employed to predict molecular initiating events, key events, and their associated phenotypes, for further understanding the relevant gene-molecule interaction toxicity pathway network. Molecular docking techniques were utilized to validate the affinity of PFAS for these molecular initiating events. An AOP framework focused on toxicological pathways was developed using classical AOP methodologies. Results The PI3K-AKT/MAPK signaling pathway was identified as a potential toxicological pathway involved in PFAS-related RB development, based on KEGG and a priori knowledge. The activation of receptor tyrosine kinases (RTKs) served as the molecular initiating event, leading to the activation of key oncogenes such as RAS and AKT, as well as nuclear factor kappa-light chainenhancer of activated B cells (NF-κB), along with the inhibition of the tumor suppressor gene P53. In this study, 14 types of PFAS demonstrated good binding affinity with most RTKs, with chlorinated polyfluorinated ether sulfonates (Cl-PFESAs) showing particularly favorable predicted binding. Oncogenes, including the c-kit-encoded tyrosine kinase receptor for stem cell factor, epidermal growth factor receptor, and neurotrophic tyrosine kinase receptor 1, were identified as the receptors with the best predicted binding affinity. Conclusion The PI3K-AKT/MAPK signaling pathway may serve as a potential toxicological mechanism linking PFAS to an increased risk of RB.

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.