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To provide evidence on the effects of vitamin D supplementation on knee osteoarthritis (KOA) and new targets for clinical prevention and treatment of KOA. The PubMed, Embase, Web of science, Wanfang, CNKI and SinoMed databases were retrieved to investigate the effects of vitamin D supplementation on patients with KOA. The search time was from databases establishment to 15 November 2020. RevMan5.3 software was used for meta-analysis. The results were expressed as standardized mean difference (SMD) with 95% confidence interval (CI) or weighted mean difference (WMD) with 95% confidence interval (CI). A total of 1599 patients with osteoarthritis of the knee were included in the study, which involved six articles. The results of the meta-analysis showed that vitamin D supplementation is statistically significant for WOMAC score (SMD = -0.67, 95% CI -1.23 to -0.12) in patients with KOA, including WOMAC pain score (SMD = -0.32, 95% CI -0.63 to -0.02), function score (SMD = -0.34, 95% CI -0.60 to -0.08) and stiffness score (SMD = -0.13, 95% CI -0.26 to -0.01). In subgroup analysis, vitamin D supplementation less than 2000IU was statistically significant for the reduction of stiffness score (SMD = -0.22, 95% CI -0.40 to -0.04). Vitamin D supplements can reduce synovial fluid volume progression in patients with KOA (SMD = -0.20, 95% CI -0.39 to -0.02). There was no statistical significance in improving tibia cartilage volume (SMD = 0.12, 95% CI -0.05 to 0.29), joint space width (SMD = -0.10, 95% CI -0.26 to 0.05) and bone marrow lesions (SMD = 0.03, 95% CI -0.26 to 0.31). Vitamin D supplements can improve WOMAC pain and function in patients with KOA. But there is a lack of strong evidence that vitamin D supplementation can prevent structural progression in patients with KOA.Vitamin D supplements can improve WOMAC pain and function in patients with KOA. But there is a lack of strong evidence that vitamin D supplementation can prevent structural progression in patients with KOA. The successful treatment of Graves' ophthalmopathy (GO) remains a challenge, while the efficacy of rituximab (RTX) is at present controversial. The aim of this meta-analysis was to investigate the potential impact of intravenous RTX therapy in patients with GO. We performed a search in the PubMed, Embase, and Web of Science databases for relevant studies published before July 2020. https://www.selleckchem.com/products/itd-1.html The primary outcome was the change of clinical activity score (CAS), and secondary outcomes were the change of proptosis and TSH receptor antibodies (TRAb). A meta-analysis was conducted to calculate the standard mean difference (SMD) for these outcomes by using fixed- or random-effect models. Analysis of outcomes in 152 patients collected from 12 published articles was conducted. Compared to baseline value, CAS was significantly decreased at 1, 6, 12, and >12 months after RTX treatment. For proptosis, the results revealed no significant decrease at 1-3, 6, and ≥12 months. Moreover, the pooled analysis employed in this meta-analysis showed no significant difference of TRAb at 1 month, but significant declines were observed at 6 and ≥12 months. Our results strongly suggest that intravenous RTX treatment has an acute and long-lasting beneficial effect on decreasing both CAS and TRAb. The study also indicates that the effect of RTX on proptosis is limited. There is evidently a need to investigate the mechanism behind RTX ineffectiveness on proptosis and explore other therapeutic regimens for the reduction of proptosis.Our results strongly suggest that intravenous RTX treatment has an acute and long-lasting beneficial effect on decreasing both CAS and TRAb. The study also indicates that the effect of RTX on proptosis is limited. There is evidently a need to investigate the mechanism behind RTX ineffectiveness on proptosis and explore other therapeutic regimens for the reduction of proptosis.Extracellular cold-inducible RNA-binding protein (eCIRP) stimulates microglial inflammation causing neuronal damage during ischemic stroke and is a critical mediator of alcohol-induced cognitive impairment. However, the precise role of eCIRP in mediating neuroinflammation remains unknown. In this study, we report that eCIRP activates neurotoxic cyclin-dependent kinase-5 (Cdk5)/p25 through the induction of IL-6Rα/STAT3 pathway in neurons. Amyloid β (Aβ)-mediated neuronal stress, which is associated with Alzheimer's disease, increased the levels of eCIRP released from BV2 microglial cells. The released eCIRP levels from BV2 cells increased 3.2-fold upon stimulation with conditioned medium from Neuro-2a (N2a) cells containing Aβ compared to control N2a supernatant in a time-dependent manner. Stimulation of N2a cells and primary neurons with eCIRP upregulated the neuronal Cdk5 activator p25 expression in a dose- and time-dependent manner. eCIRP directly induced neuronal STAT3 phosphorylation and p25 increase via its novel receptor IL-6Rα. Next, we showed using surface plasmon resonance that eCIRP-derived peptide C23 inhibited the binding of eCIRP to IL-6Rα at 25 μM, with a 40-fold increase in equilibrium dissociation constant (Kd) value (from 8.08 × 10-8 M to 3.43 × 10-6 M), and completely abrogated the binding at 50 μM. Finally, C23 reversed the eCIRP-induced increase in neuronal STAT3 phosphorylation and p25 levels. In conclusion, the current study demonstrates that the upregulation of neuronal IL-6Rα/STAT3/Cdk5 pathway is a key mechanism of eCIRP's role in neuroinflammation and that C23 as a potent inhibitor of this pathway has translational potential in neurodegenerative pathologies controlled by eCIRP.Accurate estimate of riverine material fluxes in dissolved and suspended particulate forms is a fundamental issue in monitoring water environments of large basins. Here we collected sub-daily observations of dissolved pollutants (NO3--N, NH4+-N, and DOC) and daily data of suspended sediment (SS) at eight gauging stations with controlling areas varied from 694,700 to 1,705,400 km2 located in the Yangtze River basin of China, and selected optimal estimates for both dissolved and suspended particulate material fluxes from five time-averaging methods and two regression methods. The results showed that time-averaging methods generally performed better in estimating dissolved pollutants, while regression methods were more applicable for suspended particulate materials. Compared with the selected optimal methods, the conventional method generally overestimated material fluxes by 0.09-49.75% in most cases. Longer sampling interval and smaller controlling area often led to larger uncertainty in estimation and critical values of sampling interval and controlling area were generally found to be 10-20 days and 1.