Objective: To analyze the relationship between fatigue and self- efficacy and empowerment in patients with rheumatoid arthritis. Methods: A total of 219 cases of rheumatoid arthritis were investigated by general data questionnaire, Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire, Chinese Version of Patient Perception of Empowerment Scale and Chinese Version of Arthritis Self-efficacy Scale-8. SPSS 20.0 software was used for correlation analysis and AMOS software was used to construct structural equation model to test the mediating effect of self-efficacy between empowerment level and fatigue in patients with rheumatoid arthritis. Results: There was a significant negative correlation between fatigue and empowerment level (r=-0.62, P <0.05), and a significant correlation between fatigue and self-efficacy (r=-0.81, P <0.05). Self-efficacy had a mediating effect on empowerment level and fatigue in patients with rheumatoid arthritis, and the mediating effect accounted for 96.41% of the total effect. Conclusions Self-efficacy has mediating effect between powerment level and fatigue in patients with rheumatoid arthritis.

OBJECTIVE: To explore the genetic basis for a pedigree affected with hereditary multiple osteochondroma (HMO). METHODS: Peripheral blood samples were collected from the proband and members of his pedigree with informed consent. Following extraction of genomic DNA, all coding exons and flanking intronic sequences (-10 bp) of the EXT1 and EXT2 genes were subjected to targeted capture and next generation sequencing (NGS). Suspected variant was verified by Sanger sequencing. RESULTS: A heterozygous nonsense variant (c.1911C>A) was found in exon 10 of the EXT1 gene in the proband and his affected father but not in a healthy sister and normal controls. The variant was classified as a pathogenic based on the guidelines of the American College of Medical Genetics and Genomics (PVS1+PM2+PP1). Bioinformatic analysis predicted that the c.1911C>A variant may be disease-causing via nonsense-mediated mRNA decay and anomalous splicing. CONCLUSION The c.1911C>A variant probably underlay the disease in this pedigree. Discovery of this variant enriched the variant spectrum of HMO.
Codon, Nonsense ; Exons/genetics* ; Exostoses, Multiple Hereditary/genetics* ; Heterozygote ; Humans ; Pedigree

Background/Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become an increasingly important health challenge, with a substantial rise linked to changing lifestyles and global obesity. Ursolic acid, a natural pentacyclic triterpenoid, has been explored for its potential therapeutic effects. Given its multifunctional bioactive properties, this research further revealed the pharmacological mechanisms of ursolic acid on MASLD. Methods: Drug target chips and bioinformatics analysis were combined in this study to explore the potential therapeutic effects of ursolic acid on MASLD. Molecular docking simulations, surface plasmon resonance analyses, pull-down experiments, and co-immunoprecipitation assays were used to verify the direct interactions. Gene knockdown mice were generated, and high-fat diets were used to validate drug efficacy. Furthermore, initial CD4+ T cells were isolated and stimulated to demonstrate our findings. Results: In this study, the multifunctional extracellular matrix phosphorylated glycoprotein secreted phosphoprotein 1 (SPP1) was investigated, highlighting its capability to induce Th17 cell differentiation, amplifying inflammatory cascades, and subsequently promoting the evolution of MASLD. In addition, this study revealed that in addition to the canonical TGF-β/IL-6 cytokine pathway, SPP1 can directly interact with ITGB1 and CD44, orchestrating Th17 cell differentiation via their joint downstream ERK signaling pathway. Remarkably, ursolic acid intervention notably suppressed the protein activity of SPP1, suggesting a promising avenue for ameliorating the immunoinflammatory trajectory in MASLD progression. Conclusions Ursolic acid could improve immune inflammation in MASLD by modulating SPP1-mediated Th17 cell differentiation via the ERK signaling pathway, which is orchestrated jointly by ITGB1 and CD44, emerging as a linchpin in this molecular cascade.

Objective: To observe the effect of Huangjing Zanyu Capsule (HZC) on sperm mitochondrial membrane potential (MMP) in asthenozoospermia patients. METHODS: We assigned 70 asthenozoospermia patients to a treatment group (n = 39) and a control group (n = 31), the former treated with oral HZC at the dose of 4 capsules tid for 3 months while the latter left untreated. We obtained semen parameters from the patients and detected their sperm mitochondrial membrane potentials (MMP) by JC-1 staining and flow cytometry before and after medication, followed by comparison between the two groups. RESULTS: The total effectiveness rate was 71.05% in the treatment group and natural pregnancy was achieved in 3 cases during the medication. A total of 35 patients in the treatment group and 30 controls completed all the laboratory examinations after a 3-month observation. Compared with the controls, the patients treated with HZC exhibited significant improvement after medication in MMP (variation value: ［1.19 ± 10.36］% vs ［20.28 ± 14.21］%, P <0.01), total sperm motility (variation value: ［3.46 ± 8.67］% vs ［20.68 ± 14.12］%, P <0.01), the percentage of progressively motile sperm (variation value: ［2.26 ± 8.29］% vs ［17.58 ± 12.73］%, P <0.01), and the percentage of morphologically normal sperm (variation value: ［0.23 ± 3.48］% vs ［3.37 ± 3.99］%, P <0.01). MMP was significantly correlated with total sperm motility (r = 0.69, P <0.01), progressive sperm motility (r = 0.75, P <0.01) and normal sperm morphology (r = 0.26, P <0.01). CONCLUSIONS Huangjing Zanyu Capsule can enhance sperm mitochondrial membrane potential and sperm mitochondrial function, thus improving total sperm motility, progressive sperm motility and normal sperm morphology. It is safe and effective for the treatment of asthenospermia.
Asthenozoospermia ; drug therapy ; Capsules ; Case-Control Studies ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Female ; Flow Cytometry ; Humans ; Male ; Membrane Potential, Mitochondrial ; drug effects ; physiology ; Pregnancy ; Semen ; drug effects ; Sperm Motility ; drug effects ; Spermatozoa ; drug effects ; ultrastructure ; Staining and Labeling

Aging poses a major risk factor for cardiovascular diseases, the leading cause of death in the aged population. However, the cell type-specific changes underlying cardiac aging are far from being clear. Here, we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age. We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profiles. Via transcription regulatory network analysis, we identified FOXP1, a core transcription factor in organ development, as a key downregulated factor in aged cardiomyocytes, concomitant with the dysregulation of FOXP1 target genes associated with heart function and cardiac diseases. Consistently, the deficiency of FOXP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes. Altogether, our findings depict the cellular and molecular landscape of ventricular aging at the single-cell resolution, and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.
Aged ; Animals ; Humans ; Aging/genetics* ; Forkhead Transcription Factors/metabolism* ; Myocytes, Cardiac/metabolism* ; Primates/metabolism* ; Repressor Proteins/metabolism* ; Transcriptome ; Macaca fascicularis/metabolism*