Objective: We conducted the updated systematic review and meta-analysis of the best available quantitative and qualitative evidence to evaluate the effects and safety of duloxetine for the treatment of knee osteoarthritis (OA) pain. Methods: A comprehensive literature search used 3 English and 4 Chinese biomedical databases from inception through July 10, 2020. We included randomized controlled trials of duloxetine with intervention duration of 2 weeks or longer for knee OA. The primary outcome was pain intensity measured by Brief Pain Inventory and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. Secondary outcome measurements included 36-Item Short Form Health Survey, Patient’s Global Impression of Improvement, Clinical Global Impressions of Severity, and adverse events (AEs). The quality of all included studies was evaluated using the Cochrane risk-of-bias criteria. The review was registered in the PROSPERO (CRD 42020194072). Results: Six studies totaling 2059 patients met the eligibility criteria. Duloxetine had significant reductions in Brief Pain Inventory 24 hours average pain (mean difference [MD]=−0.74; 95% confidence interval [CI], −0.92 to −0.57; P <0.00001; I 2 =13%; 5 trials; 1695 patients); patient general activity (MD=−0.76; 95% CI, −0.96 to −0.56; P <0.00001; I 2 =0%; 5 trials; 1694 patients) WOMAC physical function subscale (MD=−4.22; 95% CI, −5.14 to −3.30; P <0.00001; I 2 =26%; 5 trials; 1986 patients); Patient’s Global Impression of Improvement (MD=−0.48; 95% CI, −0.58 to −0.37; P <0.00001; I 2 =29%; 5 trials; 1741 patients); and Clinical Global Impressions of Severity (MD=−0.34; 95% CI, −0.44 to −0.24; P <0.00001; I 2 =0%; 4 trials; 1178 patients) compared with placebo control. However, no difference on WOMAC pain subscale (standard mean difference=−1.68; 95% CI, −3.45 to 0.08; P =0.06; I 2 =100%; 3 trials; 1104 patients) and in serious AEs (risk ratio=0.92; 95% CI, 0.40-2.11; P =0.84; I 2 =0%; 5 trials; 1762 patients) between duloxetine and placebo. Furthermore, duloxetine failed to show superior effects for improving the life quality and demonstrated more treatment-emergent AEs. Conclusion: Duloxetine may be an effective treatment option for knee OA patients but further rigorously designed and well-controlled randomized trials are warranted.

Aim of the study: A discussion of the effect of Shi-style steaming and bathing decoction on synovial fibrosis and vascular hyperplasia. Materials and methods An anterior cruciate ligament transection (ACLT method) was used to replicate the knee osteoarthritis (KOA) model. After 4 weeks, and synovial tissues were taken for hematoxylin-eosin staining (HE) and Krenn score to verify whether the KOA model was successfully established. After the 4-week successful modeling, each group used different interventions for 4 weeks, while the sham-operated and KOA model groups were not intervened. At the end of the intervention, HE staining and Masson staining were used and Krenn scores and positive fiber areas were calculated.Femoral artery blood flows in the right lower limb was detected with a color Doppler ultrasound machine. The protein expression level of VEGFA was determined by enzyme-linked immunosorbent assay and immunohistochemical assay, and the quantitatively analyze the mRNA of VEGFA using Real-time PCR . Results The animals in Shi-style steaming and bathing decoction herbal bath treatment group generally performed well. HE staining, Krenn score and Masson staining indicated that Shi-style steaming and bathing decoction herbal baths reduced the number of synovial inflammatory cells, attenuated synovial fibrosis, decreased blood flow velocity, alleviated vascular resistance, and decreased the protein expression level of VEGFA in vivo and the mRNA expression level. Conclusions In the rabbit KOA model, Shi-style steaming and bathing decoction herbal bath at 40°C can alleviate synovial inflammation, fibrosis and revascularization, and improve local blood circulation of the knee joint. Therefore, it is feasible for the treatment of knee osteoarthritis.