Connective tissue growth factor (CTGF), also known as CCN2, is a key proinflammatory mediator. In the present study, the involvement of the CTGF signaling pathway in human knee osteoarthritis (OA) fibroblast-like synoviocytes (FLSs) was investigated. FLSs were isolated from human OA synovium and incubated with CTGF in the absence or presence of interleukin‑1β (IL‑1β). The expression of relevant genes and proteins was analyzed by qPCR, western blotting and enzyme-linked immunosorbent assay (ELISA). Matrix metalloproteinase (MMP) activity and nuclear factor (NF)-κB activation were also evaluated. CTGF stimulation resulted in the significant production of IL-6, IL-8, C-C motif ligand 2 (CCL2), CCL20, MMP-1 and MMP-3 in FLSs in the presence, but not in the absence, of IL-1β. CTGF also enhanced the levels of phosphorylated extracellular signal-related kinase 1/2 (ERK1/2) and p38. In addition, CTGF at 25 ng/ml, in the presence of IL‑1β, significantly potentiated NF-κB activation. The results indicated that CTGF interacted with IL‑1β in FLSs to promote the inflammatory response in the synovium, leading to the initiation of the inflammatory cascade. These results support the proinflammatory role of CTGF in synovitis and joint destruction in OA.

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<p style='text-indent:20px;'>This paper presents an effective algorithm for globally solving the sum of linear ratios problem (SLRP), which has broad applications in government planning, finance and investment, cluster analysis, game theory and so on. In this paper, by using a new linearization technique, the linear relaxation problem of the equivalent problem is constructed. Next, based on the linear relaxation problem and the branch-and-bound framework, an effective branch-and-bound algorithm for globally solving the problem (SLRP) is proposed. By analyzing the computational complexity of the proposed algorithm, the maximum number of iterations of the algorithm is derived. Numerical experiments are reported to verify the effectiveness and feasibility of the proposed algorithm. Finally, two practical application problems from power transportation and production planning are solved to verify the feasibility of the algorithm.</p>

This paper presents a rectangular branch-and-reduction algorithm for globally solving indefinite quadratic programming problem (IQPP), which has a wide application in engineering design and optimization. In this algorithm, first of all, we convert the IQPP into an equivalent bilinear optimization problem (EBOP). Next, a novel linearizing technique is presented for deriving the linear relaxation programs problem (LRPP) of the EBOP, which can be used to obtain the lower bound of the global optimal value to the EBOP. To obtain a global optimal solution of the EBOP, the main computational task of the proposed algorithm involves the solutions of a sequence of LRPP. Moreover, the global convergent property of the algorithm is proved, and numerical experiments demonstrate the higher computational performance of the algorithm.