Background: Previous clinical trials indicated that duloxetine may be effective in the treatment of osteoarthritis (OA) pain. This meta-analysis is conducted to evaluate short term analgesic effect and safety of duloxetine in the treatment of OA. Methods: Electronic databases were searched in February 2019, including PUBMED, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science. All eligible studies should be randomized controlled trials (RCTs) comparing duloxetine treatment group to placebo about OA pain relief and safety outcomes. Results: Five RCTs with 2059 patients were involved in this systematic review and meta-analysis. Compared to placebo, duloxetine treatment showed significant better result, with higher reduction pain intensity (mean difference [MD] = –0.77, P < .00001), higher rates of both 30% and 50% reduction in pain severity (risk ratio [RR] = 1.42, P < .00001; RR = 1.62, P < .00001), lower mean Patient Global Improvement-Inventory (PGI-I) score (MD = –0.48, P < .00001). The results of the Western Ontario and McMaster Universities (WOMAC) score change from baseline to endpoint also favored duloxetine treatment group in all four categories, including total (MD = –5.43, P < .00001), pain (MD = –1.63, P = .001), physical function (MD = –4.22, P < .00001), and stiffness score (MD = –0.58, P < .00001). There were higher rates of treatment-emergent adverse events (TEAEs) (RR = 1.32, P < .00001) and discontinuation (RR = 1.88, P < .00001) in duloxetine group. However, there was no significant difference in the incidence of severe adverse events (SAEs) between these 2 groups (RR = 0.84, P = .68). Conclusion: Duloxetine was an effective and safe choice to improve pain and functional outcome in OA patients. However, further studies are still needed to find out the optimal dosage for OA and examine its long-term efficacy and safety. Trial registration number: CRD42019128862
Neuropilin-1 (NRP-1) is involved in a range of physiological and pathological processes, including neuronal cell guidance, cardiovascular development, immunity, angiogenesis and the pathogenesis of cancer. Targeting of NRP-1 is considered to be a potential cancer therapy and a number of approaches have been investigated, including the use of small interfering RNA, peptides, soluble NRP antagonists and monoclonal antibodies. The present study used a novel anti-neuropilin-1 monoclonal antibody (anti-NRP-1 mAb) to investigate its potential anti-tumor effects on human gastric cancer cells in vitro and in vivo, as well as its underlying mechanisms of action. Using an MTT assay, it was observed that anti-NRP-1 mAb (<150 µg/ml) had no effects on the viability of gastric cancer cell line BGC-823, while a Boyden chamber assay indicated that treatment with anti-NRP-1 mAb suppressed the migration and invasion of BGC-823 cells. Western blot analysis also demonstrated that phosphorylation of Akt was reduced in BGC-823 cells treated with anti-NRP-1 mAb. Furthermore, anti-NRP-1 mAb suppressed the growth of gastric cancer xenograft tumors and downregulated the expression of vascular endothelial growth factor proteins within tumors in nude mice. These data indicate the potential effects of anti-NRP-1 mAb on malignant tumors and suggest that inhibition of NRP-1 function with anti-NRP-1 mAb may be a novel therapeutic approach in the treatment of cancer.
ObjectivesLow-density lipoprotein cholesterol (LDL-C) plays an essential part in bone metabolism. However, the correlation between LDL-C levels and bone mineral density (BMD) is still controversial. This study aimed to explore the relationship between LDL-C levels and lumbar BMD in young- and middle-aged people.MethodsWe conducted a cross-sectional study comprising 4,441 participants aged 20–59 from the National Health and Nutrition Examination Survey (NHANES). LDL-C levels and lumbar BMD were used as independent and dependent variables, respectively. We evaluated the correlation between LDL-C levels and lumbar BMD through a weighted multivariate linear regression model. We performed a subgroup analysis of the relationship between LDL-C levels and lumbar BMD based on age, gender, and body mass index (BMI).ResultsAfter adjusting for confounding factors, LDL-C levels were negatively correlated with lumbar BMD. In subgroup analyses stratified by gender, this negative association was statistically significant in men and women. In the subgroup analysis stratified by age, a negative connection existed in people aged 30–49 years. In the subgroup analysis divided by BMI, there was an inverse correlation in overweight people (25 ≤ BMI < 30).ConclusionsOur research observed an inverse association between LDL-C levels and lumbar BMD in young- and middle-aged people, especially in people aged 30–49 years and who are overweight. Close monitoring of BMD and early intervention may be required for these people.
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