Uric acid (UA) is the final oxidation product of purine metabolism. Hyperuricemia has been previously reported to contribute to vascular endothelial dysfunction and the development of cardiovascular diseases, metabolic syndrome and chronic kidney diseases. In addition, it has been reported that fibroblast growth factor 21 (FGF21) can exert regulatory effects on UA-induced lipid accumulation. Therefore, the present study aimed to investigate the possible role of FGF21 in HUVEC cell injury induced by UA. The study used UA to induce HUVEC cell injury, inhibited sirtuin 1 (Sirt1) expression using EX527 and overexpressed FGF21 by transfection. Subsequently, reverse transcription-quantitative PCR was performed to measure the mRNA expression levels of FGF21, Sirt1 and inflammatory cytokines TNF-α, IL-1β and IL-6, whereas western blotting was performed to measure their corresponding protein expression levels including FGF21, Sirt1, NLR family pyrin domain containing 3, pro-caspase1, apoptosis-associated speck-like protein containing a CARD, activating transcription factor 4, C/EBP homologous protein and eukaryotic initiation factor 2. Furthermore, dichloro-dihydro-fluorescein diacetate staining was performed to measure intracellular reactive oxygen species (ROS) generation in HUVECs. The levels of ROS and nitric oxide were also quantified using commercial assay kits. The results demonstrated that overexpression of FGF21 significantly inhibited UA treatment-induced endoplasmic reticulum (ER) stress, inflammation and oxidative stress in HUVECs. Furthermore, overexpression of FGF21 significantly activated Sirt1. The sirt1 inhibitor, EX527, significantly abrogated the suppressive effects of FGF21 overexpression on ER stress, inflammation and oxidative stress in UA-stimulated HUVECs. To conclude, results of the present study suggested that FGF21 may attenuate UA-induced ER stress, inflammation and vascular endothelial cell dysfunction by activating Sirt1. Therefore, FGF21 may be a potential effective target for the future treatment of vascular endothelial cell dysfunction.

Leflunomide (LEF) is a conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for the treatment of rheumatoid arthritis. However, there are few reports on the comparison of efficacy between LEF alone and combined with other csDMARDs. Here, the efficacy and safety of LEF monotherapy (88) and combination (361) therapy groups were evaluated. After 3 months, there were no significant differences in 28-joint disease activity score (DAS28), health assessment questionnaire (HAQ), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) between the monotherapy and combination groups (all P > 0.05). According to the European League Against Rheumatism (EULAR) response criteria, it was found that the DAS28 response rates were similar in the two groups (P > 0.05). Besides, the two groups presented similar safety profiles. Subgroup analysis found that there was no difference in efficacy among the three combined therapies (LEF + methotrexate (MTX), LEF + hydroxychloroquine (HCQ), and LEF + MTX + HCQ) and LEF monotherapy. Furthermore, when the dose of LEF was less than 40 mg/day, no significant difference in efficacy was observed between low and high doses. Overall, these results indicated that low dose LEF monotherapy was not inferior to the combination therapy. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovitis, and its primary clinical manifestations is symmetric arthritis affecting multiple joints. Inflammation and joint erosion cause physical function disorder, which severely reduces the quality of life. The global prevalence of RA is 0.5-1% 1,2 , the incidence of RA among females is 2 to 3 times than of males, and the incidence in females shows an increasing trend 3,4. Although multiple studies have reported that the occurrence of RA is related to environmental, hormonal and genetic factors 5-7 , the specific pathogenesis of RA remains unclear, which is difficult to achieve radical cure. The main goal of treating RA at present is to control and alleviate the disease. Currently, drugs for treating RA mainly include conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), targeted synthetic DMARDs (tsDMARDs), biological DMARDs (bDMARDs), biosimilar DMARDs (bsDMARDs), and glucocorticoids (GCs) 8. Economical and effective csDMARDs are the first treatment strategy recommended by the European League Against Rheumatism (EULAR) 8 , including leflunomide (LEF), methotrexate (MTX), hydroxychloroquine (HCQ), sulfasalazine (SSZ), cyclosporine, azathioprine and gold salts. Among them, LEF was approved by the Food and Drug Administration for the treatment of RA in 1998 and plays a role in controlling and relieving the condition of the disease through acting on dihydroorotate

A hybrid method for synthesizing antenna's three di mensional (3�) pattern is proposed to obtain the low sidelobe feature of truncated cone conformal phased arrays. In this method, the elements of truncated cone conformal phased arrays are pro jected to the tangent plane in one generatrix of the truncated cone. Then two dimensional (20) Chebyshev amplitude distribution optimization is respectively used in two mutual vertical directions of the tangent plane. According to the location of the elements, the excitation current amplitude distribution of each element on the conformal structure is derived reversely, then the excitation cur rent amplitude is further optimized by using the genetic algorithm (GA). A truncated cone problem with 8 x 8 elements on it, and a 3D pattern desired side lobe level (SLL) up to 35 dB, is studied. By using the hybrid method, the optimal goal is accomplished with acceptable CPU time, which indicates that this hybrid method for the low side lobe synthesis is feasible.

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