Interaction effects of significant risk factors on low bone mineral density in ankylosing spondylitis.

Background: To analyze individually and interactively critical risk factors, which are closely related to low bone mineral density (BMD) in patient with ankylosing spondylitis (AS). Methods: A total of 249 AS patients who visited China-Japan Friendship Hospital were included in this training set. Patients with questionnaire data, blood samples, X-rays, and BMD were collected. Logistic regression analysis was employed to identify key risk factors for low BMD in different sites, and predictive accuracy was improved by incorporating the selected significant risk factors into the baseline model, which was then validated using a validation set. The interaction between risk factors was analyzed, and predictive nomograms for low BMD in different sites were established. Results: There were 113 patients with normal BMD, and 136 patients with low BMD. AS patients with hip involvement are more likely to have low BMD in the total hip, whereas those without hip involvement are more prone to low BMD in the lumbar spine. Chest expansion, mSASSS, radiographic average grade of the sacroiliac joint, and hip involvement were significantly associated with low BMD of the femoral neck and total hip. Syndesmophytes, hip involvement and higher radiographic average grade of the sacroiliac joint increases the risk of low BMD of the femoral neck and total hip in an additive manner. Finally, a prediction model was constructed to predict the risk of low BMD in total hip and femoral neck. Conclusions: This study identified hip involvement was strongly associated with low BMD of the total hip in AS patients. Furthermore, the risk of low BMD of the femoral neck and total hip was found to increase in an additive manner with the presence of syndesmophytes, hip involvement, and severe sacroiliitis. This finding may help rheumatologists to identify AS patients who are at a high risk of developing low BMD and prompt early intervention to prevent fractures.

Eosinophilic fasciitis difficult to differentiate from scleroderma: A case report.

BACKGROUND: Eosinophilic fasciitis (EF) is a rare connective tissue disease that can cause swelling and sclerosis of the extremities, and special attention is needed to differentiate EF from systemic sclerosis. Misdiagnosis or omission markedly delays treatment of EF, and severe skin sclerosis in advanced stages can cause joint contracture and tendon retraction, worsening the patient's prognosis and quality of life. CASE SUMMARY: We report a case of EF in a young woman diagnosed by tissue biopsy, confirming the difficulty of differential diagnosis with scleroderma. CONCLUSION: Focusing on skin manifestations, completing tissue biopsy and radiography can help diagnose EF effectively. Clinicians should enhance their understanding of the differences between EF and scleroderma, and early diagnosis and standardized treatment can improve the prognosis of patients with EF.

Role and mechanism of fibroblast-activated protein-α expression on the surface of fibroblast-like synoviocytes in rheumatoid arthritis.

Fibroblast-activated protein-α (FAP) is a type II integrated serine protease expressed by activated fibroblasts during fibrosis or inflammation. Fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) synovial sites abundantly and stably overexpress FAP and play important roles in regulating the cellular immune, inflammatory, invasion, migration, proliferation, and angiogenesis responses in the synovial region. Overexpression of FAP is regulated by the initial inflammatory microenvironment of the disease and epigenetic signaling, which promotes RA development by regulating FLSs or affecting the signaling cross-linking FLSs with other cells at the local synovium and inflammatory stimulation. At present, several treatment options targeting FAP are in the process of development. This review discusses the basic features of FAP expressed on the surface of FLSs and its role in RA pathophysiology and advances in targeted therapies.

Epimedii Herba: An ancient Chinese herbal medicine in the prevention and treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, progressive inflammatory and systemic autoimmune disease resulting in severe joint destruction, lifelong suffering and considerable disability. Diverse prescriptions of traditional Chinese medicine (TCM) containing Epimedii Herba (EH) achieve greatly curative effects against RA. The present review aims to systemically summarize the therapeutic effect, pharmacological mechanism, bioavailability and safety assessment of EH to provide a novel insight for subsequent studies. The search terms included were "Epimedii Herba", "yinyanghuo", "arthritis, rheumatoid" and "Rheumatoid Arthritis", and relevant literatures were collected on the database such as Google Scholar, Pubmed, Web of Science and CNKI. In this review, 15 compounds from EH for the treatment of RA were summarized from the aspects of anti-inflammatory, immunoregulatory, cartilage and bone protective, antiangiogenic and antioxidant activities. Although EH has been frequently used to treat RA in clinical practice, studies on mechanisms of these activities are still scarce. Various compounds of EH have the multifunctional traits in the treatment of RA, so EH may be a great complementary medicine option and it is necessary to pay more attention to further research and development.

Does education finance reduce the inequality of educational results? The mediation effect of shadow education.

Public education finance in China plays an important role in education equality. This study investigated two mediation effects with a generalized structural equation model that comprised the mediation effect of shadow education at the school, family, and individual levels and the moderating role of education finance. There was a strong association among heterogeneity factors, shadow education, and educational results, with shadow education playing a mediating role in math and English courses. Individual heterogeneity differences had a negative impact on equality in educational results through access to additional shadow education opportunities, while heterogeneous factors were mediated through shadow education, causing financial moderation effects, in turn affecting inequality in educational results. Finally, the moderation degree and direction of education finance varied significantly, with a greater moderation effect on household-level factors that lead to unequal educational results. Targeted efforts are required to regulate shadow education, which is key to the development of the education system.

Leukemia inhibitory factor is dysregulated in ankylosing spondylitis and contributes to bone formation.

AIM: Ankylosing spondylitis (AS) is a chronic inflammatory disease. However, the key inflammatory cytokines disrupted in this disease are not well defined. In this study, we performed protein array and multiple protein quantification to investigate the differentially expressed cytokines in plasma between AS patients and healthy subjects. METHOD: In the discovery cohort, 5 AS patients who never underwent biologic therapy and 5 gender- and age-matched healthy subjects were enrolled in the protein array analysis. Another 40 AS patients and 20 healthy participants were recruited in the validation stage. In addition, the messenger RNA and protein levels of osteogenesis-related genes were quantified in hFOB1.19 cells in an in vitro osteoblast model. RESULTS: Of the 318 cytokines found to be differentially expressed by protein array, leukemia inhibitor factor (LIF) was significantly increased in AS patients as compared to controls. The "signaling by interleukins" pathway was the most enriched pathway in AS patients, and "signaling by interleukins"-related cytokines, including LIF, interleukin (IL)-6, IL-23, and IL-31, were significantly differentially expressed in the validation stage. Additionally, we correlated the expression of LIF with C-reactive protein (CRP) and inflammation of magnetic resonance imaging lesions in the spine (MRI-SPINE) in AS patients. We further analyzed the effects of LIF in hFOB cells and found that LIF promoted the growth factor receptor-bound protein 2 / phospho-extracellular signal-regulated kinase / runt-related transcription factor 2 / alkaline phosphatase pathway at the protein level and activated several osteogenesis-related genes (RUNX2 and BGLAP). CONCLUSION: LIF was increased in the plasma of AS patients as compared with healthy subjects and significantly correlated with inflammation indices (CRP and MRI-SPINE) in AS patients. Thus, LIF may play a critical role in the pathogenesis of AS via promoting osteogenic differentiation.

Prediction of Rhizoma Drynariae Targets in the Treatment of Osteoarthritis Based on Network Pharmacology and Experimental Verification.

Rhizoma Drynariae has been widely used for the treatment of osteoarthritis (OA), but its potential targets and molecular mechanisms remain to be further explored. Targets of Rhizoma Drynariae and OA were predicted by relevant databases, and a protein-protein interaction (PPI) network was constructed to identify key targets. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to obtain related pathways and then select significant pathways associated with OA. The OA chondrocyte model was established by inflammatory factor-induced SW1353 chondrocytes, and molecular docking was conducted to verify the above theoretical prediction. The results showed that a total of 86 Rhizoma Drynariae-OA interaction targets were identified, among which IL-6 and AKT1 were the key targets in the PPI network. Luteolin was the most critical component of Rhizoma Drynariae. KEGG results indicated that the effects of Rhizoma Drynariae on OA are associated with the PI3K/AKT, TNF, IL-17, apoptosis, and HIF-1 signaling pathway. The PI3K/AKT pathway can activate the downstream NF-κB pathway and further regulate the transcription and expression of downstream IL-6, IL-17, HIF-1α, Bax, and TNF, suggesting that the PI3K/AKT/NF-κB pathway is the critical pathway in the treatment of OA with Rhizoma Drynariae. Active components of Rhizoma Drynariae and key proteins of the PI3K/AKT/NF-κB signaling pathway were subjected to molecular docking, whose results showed that luteolin and IKK-α played a critical role. In vitro experiments indicated that both aqueous extracts of Rhizoma Drynariae (AERD) and luteolin inhibited the expression of IL-6 and HIF-1α and suppressed the activation of PI3K/AKT/NF-κB, IL-17, and TNF pathways. The measurement of mitochondrial membrane potential (Δψm) indicated that AERD and luteolin can decrease the LPS-induced early apoptotic cells. Luteolin had a more prominent inhibitory effect than AERD in the abovementioned in vitro experiments. In conclusion, the therapeutic mechanism of Rhizoma Drynariae against OA may be closely related to the inhibition of the PI3K/AKT/NF-κB pathway and downstream pathways, and luteolin plays a vital role in the treatment.

The geometric attention-aware network for lane detection in complex road scenes.

Lane detection in complex road scenes is still a challenging task due to poor lighting conditions, interference of irrelevant road markings or signs, etc. To solve the problem of lane detection in the various complex road scenes, we proposed a geometric attention-aware network (GAAN) for lane detection. The proposed GAAN adopted a multi-task branch architecture, and used the attention information propagation (AIP) module to perform communication between branches, then the geometric attention-aware (GAA) module was used to complete feature fusion. In order to verify the lane detection effect of the proposed model in this paper, the experiments were conducted on the CULane dataset, TuSimple dataset, and BDD100K dataset. The experimental results show that our method performs well compared with the current excellent lane line detection networks.

Total Flavonoids of Rhizoma Drynariae Restore the MMP/TIMP Balance in Models of Osteoarthritis by Inhibiting the Activation of the NF-κB and PI3K/AKT Pathways.

Total flavonoids of Rhizoma Drynariae (TFRD) have been shown to have beneficial effects on osteoarthritis (OA) clinically, but the mechanisms have not been elucidated. In this study, we investigated the effect of TFRD on articular cartilage in an OA rat model established by the Hulth method and in SW1353 chondrocytes induced by the proinflammatory factor interleukin-1ß (IL-1ß). The results showed that TFRD could alleviate the pathological changes in knee cartilage in OA model rats. In vivo, the qPCR analysis indicated that the mRNA levels of matrix metalloproteinases, MMP-1, MMP-3, and MMP-13, were decreased, while tissue inhibitor of matrix metalloproteinases- (TIMP-) 4 was increased in cartilage, and these changes could be partially prevented by TFRD. In vitro experiments showed that IL-1ß could significantly increase the expression of MMP-1, MMP-3, and MMP-13 and decrease the expression of TIMP-4 in SW1353 cells at the mRNA and protein levels. TFRD could increase the expression of MMP-3 and MMP-13 and decrease the expression of TIMP-4. Transfection of siRNA and addition of pathway inhibitors were used to clarify that inhibition of NF-κB and PI3K/AKT pathway decreased MMP-1, MMP-3, and MMP-13 and increased TIMP-4 expression. We also found that in IL-1ß-induced SW1353 cells, TFRD pretreatment had a modest inhibitory effect on p-AKT (Ser473) and reversed the increase of nuclear factor kappa-B (NF-κB) p65 in nuclear fraction and the decrease of inhibitor of NF-κB(IκB)-α in the cytosolic fraction. Further immunofluorescence confirmed that TFRD can inhibit IL-1ß-induced NF-κB p65 translocation to the nucleus to some extent. In conclusion, TFRD showed chondroprotective effects by restoring the MMP/TIMP balance in OA models by suppressing the activation of the NF-κB and PI3K/AKT pathways.

Spectrum decomposition in Gaussian scale space for uneven illumination image binarization.

Although most images in industrial applications have fewer targets and simple image backgrounds, binarization is still a challenging task, and the corresponding results are usually unsatisfactory because of uneven illumination interference. In order to efficiently threshold images with nonuniform illumination, this paper proposes an efficient global binarization algorithm that estimates the inhomogeneous background surface of the original image constructed from the first k leading principal components in the Gaussian scale space (GSS). Then, we use the difference operator to extract the distinct foreground of the original image in which the interference of uneven illumination is effectively eliminated. Finally, the image can be effortlessly binarized by an existing global thresholding algorithm such as the Otsu method. In order to qualitatively and quantitatively verify the segmentation performance of the presented scheme, experiments were performed on a dataset collected from a nonuniform illumination environment. Compared with classical binarization methods, in some metrics, the experimental results demonstrate the effectiveness of the introduced algorithm in providing promising binarization outcomes and low computational costs.

"Wang-Bi tablet, a patented Chinese medicine, maintains the balance of Th1/Th2 in mice with collagen-induced arthritis".

OBJECTIVE: To investigate the pharmacological mechanism of Wang-Bi tablets (WBTs), a Chinese patented medicine, in rheumatoid arthritis (RA) using mice with collagen-induced arthritis (CIA). METHODS: A mouse model of CIA was induced using bovine type Ⅱ collagen. WBT treatment was administered and efficacy was evaluated. The levels of interferon-γ (IFN-γ), interleukin-2 (IL-2), and interleukin-4 (IL-4) were examined using an enzyme-linked immunosorbent assay, and the proportions of Th1 and Th2 were detected using flow cytometry. T-bet and GATA-binding protein 3 (GATA3) expression were demonstrated using Western blot analysis. RESULTS: Paw swelling and the arthritis index decreased significantly following WBT treatment. Histopathological analysis revealed markedly alleviated damage to synovium tissue in the WBT and methotrexate treatment groups. WBT regulated the production of IFN-γ, IL-2, and IL-4 and modulated Th1 and Th2 cell populations, which might have been induced by the attenuation of Th1 and Th2 cell differentiation through a decrease in the expression of T-bet and an increase in the expression of GATA3 in the synovial tissue in CIA mice. CONCLUSION: These results indicate that WBT may produce a therapeutic effect on CIA through maintaining the balance of Th1/Th2 cells, which could result in a decrease in the autoinflammatory disorder observed in RA.