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Uric acid (UA) is the main metabolite of the human body. Although UA is only a product of metabolism, it is important biological regulator. Epidermal growth factor (EGF) has important biological functions. However, so far, the effect of UA on EGF's activity has not been revealed. For this, in the current study, we systematically studied the effect of OA on the biological activity of EGF. Human Umbilical Vein Endothelial Cells (HUVECs) were used as an

People are paying greater attention to their personal health as society develops and progresses, and rheumatic immunological disorders have become a serious concern that affects human health. As a result, research on a stable, trustworthy, and effective auxiliary diagnostic method for rheumatic immune disorders is critical. Machine learning overcomes the inefficiencies and volatility of human data processing, ushering in a revolution in artificial intelligence research. With the use of big data, machine learning-based application research on rheumatic immunological disorders has already demonstrated detection abilities that are on par with or better than those of medical professionals. Artificial intelligence systems are now being applied in the field of rheumatic immune disorders, with an emphasis on the identification of patient joint images. This article focuses on the use of machine learning algorithms in the diagnosis of rheumatic illnesses, as well as the practical implications of disease-assisted diagnosis systems and intelligent medical diagnosis. This article focuses on three common machine learning algorithms for research and debate: logistic regression, support vector machines, and adaptive boosting techniques. The three algorithms are used to build diagnostic models based on rheumatic illness data, and the performance of each model is assessed. According to a thorough analysis of the assessment data, the diagnostic model based on the limit gradient boosting method has the best resilience. This article presents machine learning's use and advancement in rheumatic immunological disorders, as well as new ideas for investigating more appropriate and efficient diagnostic and treatment techniques.

Rheumatoid arthritis (RA), a chronic inflammatory synovitis systemic disease, can lead to joint deformities, loss of function and even death. The pathogenesis of RA may be related to genetics, infection and/or sex hormones; however, detailed accounts of the molecular mechanisms underlying its pathogenesis are lacking. In the present study, the synovial tissues of patients with RA and healthy individuals were analyzed to identify the pathogenic signaling pathways and key candidate genes involved in RA. Gene Ontology (GO), pathway enrichment and protein-protein interaction analysis were further used to identify the differentially expressed genes (DEGs) and their potential roles in RA. Molecular docking was used to screen the potential candidate drugs for management of RA. Small interfering RNA was used for knockdown of the CD2 protein. A Cell Counting Kit-8 assay was used to detect the proliferation of cells. Changes in the levels of inflammatory cytokines were detected using ELISA. A total of 279 DEGs were identified in RA; amongst these genes, 166 and 113 were upregulated and downregulated, respectively. GO analysis revealed that the upregulated DEGs were primarily enriched in the activation of the immune and adaptive immune responses, as well as the inflammatory response. The T-cell surface antigen CD2 (CD2) was identified as the most important hub gene by selecting the most important module from the protein-protein interaction network. Knockout of CD2 reduced the damaging effects of TNF-α on synovial cells. Through in situ screening using computer-aided drug design, the triptolide derivative (5R)-5-hydroxytriptolide (LLDT-8) was determined to have the highest docking score based on the CD2 protein structure. Cell experiments showed that LLDT-8 could inhibit the expression of CD2. Cell proliferation and inflammatory cytokine assays confirmed that CD2 was the direct target of LLDT-8. Together, the results of the present study determined factors involved in the pathogenesis of RA and the important role of CD2 in this process by analyzing the DEGs in the RA process. LLDT-8 inhibited CD2 and may thus be used to treat RA. These candidate genes and signaling pathways may serve as potential targets for the clinical treatment of RA.

BACKGROUND Atrial remodeling especially in the form of fibrosis is the most important substrate of atrial fibrillation (AF). The aim of this study was to investigate the effects of doxycycline on chronic intermittent hypoxia (CIH)-induced atrial remodeling and the pathophysiological mechanisms underlying such changes. MATERIAL AND METHODS A total of 30 Sprague-Dawley rats were randomized into 3 groups: Control group, CIH group, and CIH with doxycycline treatment group. CIH rats were subjected to CIH 6 h/d for 30 days and treatment rats were administrated doxycycline while they received CIH. After the echocardiography examination, rats were sacrificed at 31 days. The tissues of atria were collected for histological and molecular biological experiments, Masson staining was used to evaluate the extent of atrial fibrosis, microRNA-21, and its downstream target phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K) were assessed. RESULTS Compared to the control group, the CIH rats showed higher atrial interstitial collagen fraction, increased microRNA-21, PI3K levels, and decreased PTEN levels. Doxycycline treatment attenuated CIH-induced atrial fibrosis, reduced microRNA-21 and PI3K, and increased PTEN. CONCLUSIONS CIH induced significant atrial remodeling, which was attenuated by doxycycline in our rat model. These changes may be explained due to alterations in the microRNA-21-related signaling pathways by doxycycline.

To evaluate the safety and efficacy in terms of infarct-related artery (IRA) patency of prourokinase (proUK) injection within 6 h after symptom onset in patients with ST-elevation myocardial infarction (STEMI). A total of 1851 patients with acute myocardial infarction were enrolled to receive thrombolytic therapy with proUK. Qualifying patients were injected with 20 mg proUK intravenously followed by intravenous infusion of 30 mg proUK within 30 min. IRA was evaluated by coronary angiography at 120 min after thrombolysis. The efficacy and safety of proUK thrombolysis were analyzed in all the enrolled patients. Successful clinical reperfusion was observed in 1580 patients (85.4%). The number of leads with ST segment elevation and the amplitude of ST segment elevation were significantly reduced within 24 h after thrombolytic therapy with proUK. Eighty-three patients (4.48%) had died by the end of follow-up (7 days after thrombolysis), and the incidences of post-infarction angina, re-infarction or reocclusion, and emergency revascularization were 15.2, 4.21, and 8.27%, respectively. The most common bleeding complication was subcutaneous or mucosal bleeding and the incidence of intracranial hemorrhage was as lower as 0.32%. The fibrinolysis therapy with proUK is efficient and safe with very low rate of bleeding complications. It provides an alternative treatment options for STEMI patients especially in settings where primary PCI cannot be offered in a timely manner.

Background To investigate associations between WW domain-containing oxidoreductase (WWOX), runt-related transcription factor 2 (RUNX2) and vascular endothelial growth factor alpha (VEGFA) in human osteosarcoma (OS). Methods Copy number aberrations of WWOX, RUNX2and VEGFA genes were detected by microarray comparative genomic hybridization (aCGH) in 10 fresh OS tissue samples. VEGFA gene alterations were also investigated and validated by fluorescence in situ hybridization (FISH) in 54 formalin-fixed and paraffin-embedded (FFPE) OS samples. Protein expression of WWOX, RUNX2 and VEGFA were examined in 54 FFPE OS samples by immunohistochemistry (IHC). Results Analysis of previously published OS aCGH data (GSE9654) and aCGH data from this study (GSE19180) identified significant deletion of WWOX in 30% (6/20) of OS samples, whilst significant increase in both RUNX2 and VEGFA gene copy numbers were detected in 55% (11/20) and 60% (12/20) of OS samples, respectively. FISH demonstrated increased VEGFA gene copy number in 65.9% (31/47) of evaluable samples, in either focal or large fragment forms. Compared with positive expression of WWOX in 38.9% of the OS samples, positive expression of RUNX2 and VEGFA protein was found in 48.1 and 75.9% of samples. Although there was no significant association between gene copy number aberration and protein expression for WWOX and RUNX2, significant positive correlation between increased VEGFA gene copy number and VEGFA protein expression was observed. Although there was no significant reverse association between WWOX and RUNX2 expression, a significantly positive relationship was observed between RUNX2 and VEGFA protein expression. Conclusions Our data show increased RUNX2 and VEGFA gene copy numbers and elevation of their respective proteins in human OS. Positive correlation of RUNX2 and VEGFA suggests that both increased VEGFA gene copy number and RUNX2 overexpression facilitate increased expression of VEGFA.