Mendelian randomization of stroke risk after total hip and knee replacements.

Objective: Previous epidemiological studies have indicated an increased risk of neurovascular diseases in patients following total hip and knee replacements. However, definitive conclusions regarding the increased risk of stroke post-replacement remain elusive. Therefore, we conducted a two-sample Mendelian randomization study to investigate the causal relationship between total hip and knee replacements and stroke. Methods: We utilized summary data from publicly available genome-wide association studies (GWAS). Data concerning total hip replacements (THR, N = 319,037) and total knee replacements (TKR, N = 252,041) were sourced from the Genetics of Osteoarthritis (GO) Consortium. Stroke-related data were obtained from the International Stroke Genetics Consortium, encompassing any stroke (AS), any ischemic stroke (AIS), large vessel ischemic stroke (LV-IS), cardioembolic ischemic stroke (CE-IS), and small vessel ischemic stroke (SV-IS). Our primary causal inference method was the inverse variance weighted (IVW) approach, supplemented by weighted median and MR-Egger regression as secondary inference methods. We utilized the MR-PRESSO global test for outlier detection, Cochran's Q statistic to assess heterogeneity, and assessed the multiplicity and stability of our findings using p-values from MR-PRESSO and MR-Egger regressions, and the leave-one-out method, respectively. Results: We identified significant genetic associations between THR and both AS (IVW p = 0.0001, OR = 1.08, 95% CI = 1.04-1.12) and AIS (IVW p = 0.0016, OR = 1.07, 95% CI = 1.03-1.12). Significant associations were also observed between TKR and AS (IVW p = 0.0002, OR = 1.08, 95% CI = 1.04-1.12), as well as AIS (IVW p = 0.0005, OR = 1.15, 95% CI = 1.06-1.24). Conclusion: Our findings genetically support an increased risk of stroke following total hip and knee replacements. However, further studies are necessary to elucidate the specific mechanisms underlying stroke episodes post-replacement.

Observation of the therapeutic effect of auricular bean pressing on early knee osteoarthritis pain: A randomized controlled trial.

BACKGROUND: In the treatment of knee osteoarthritis (KOA), there is a need for the long-term use of therapeutic drugs that reduce joint pain and have fewer adverse effects. OBJECTIVE: This study aimed to investigate the therapeutic effect of bean pressing on ear points on early KOA pain. METHODS: One hundred patients with KOA recruited at the Wenzhou Hospital of Traditional Chinese Medicine between February 2019 and May 2022 were divided randomly into a treatment group (n= 50) and control group (n= 50). Patients in the treatment group received regular rehabilitation combined with auricular bean-pressing treatment, while patients in the control group only received conventional rehabilitation treatment. The measurement indicators - knee swelling, tenderness, range of motion sign score, C-reactive protein, and the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) indexes - were recorded before and after treatment. RESULTS: On day 5 following the start of treatment, the visual analog scale (VAS) and WOMAC scores of the treatment group were significantly lower than those of the control group (P< 0.05), and the VAS and WOMAC scores in the treatment group after treatment were significantly lower than those before treatment (P< 0.05). At week 4 after the start of treatment, the dosage of nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment group was significantly lower than that in the control group (P < 0.05). No adverse events were observed during the treatment. CONCLUSIONS: Auricular bean-pressing therapy had an analgesic effect and could also alleviate mild to moderate KOA swelling, joint stiffness, and other symptoms, effectively reducing the demand for NSAIDs and improving both knee function and quality of life. The results suggested that auricular bean-pressing therapy has promising prospects in the treatment of early KOA pain.

Methyl gallate prevents oxidative stress induced apoptosis and ECM degradation in chondrocytes via restoring Sirt3 mediated autophagy and ameliorates osteoarthritis progression.

Osteoarthritis (OA) is a common age-related degenerative disease involving various pathological processes, among which apoptosis in chondrocyte and extracellular matrix (ECM) degradation are the main pathologies. Previous studies have shown that autophagy has a protective effect on apoptosis and ECM degradation in chondrocytes. Methyl gallate (MG) is a natural polyphenol from various medicinal and edible plants. Moreover, several studies have demonstrated that MG exerts multiple pharmacological effects in various diseases, including anti-inflammatory, antioxidant, and anti-apoptosis. Hence, in this study, we investigate the protective effect of MG on the pathological process of OA in cellular and mice OA model to elucidate the underlying molecular mechanism. In vitro, MG treatment inhibits the expression of pro-apoptotic proteins and promotes the expression of anti-apoptotic proteins under TBHP stimulation. Meanwhile, MG treatment promotes the expression of Collagen II and Aggrecan and inhibits the expression of matrix-degrading enzymes thrombospondin motifs 5 (ADAMTS5) and matrix metalloproteinase-13 (MMP13), which lead to ECM degradation. Furthermore, in terms of mechanism, MG treatment enhances autophagy by upregulating SIRT3 expression, and inhibition of autophagy could eliminate the protective effect of MG on chondrocytes in terms of anti-apoptosis and ECM synthesis. The protective effect of MG on OA has also been observed in mice OA model. In brief, our study suggests that MG could be a potential candidate for the treatment of OA.

Anti­inflammatory effects of gambogic acid in murine collagen­induced arthritis through PI3K/Akt signaling pathway.

Garcinia angustifolia is a dry resin secreted by Garcinia cambogia, which has the functions of breaking blood, detoxifying, stopping bleeding and killing insects. It is used for the treatment of cancer and brain edema. Gambogic acid is the primary active ingredient. The present study aimed to investigate the anti­inflammatory and antiproliferative effects of gambogic acid on arthritis and the possible mechanisms. It was demonstrated that gambogic acid decreased arthritic scores in murine collagen­induced arthritic mice. The tumor necrosis factor (TNF)­α, interleukin (IL)­1ß, IL­6 and IL­18 concentrations, and caspase­3 and caspase­9 were significantly inhibited by gambogic acid in arthritic mice. Gambogic acid decreased matrix metalloproteinases (MMP)­2, MMP­9, nuclear factor (NF)­κB and phosphorylated­p38 protein expression, and increased tissue inhibitors of matrix metalloproteases­1 (TIMP­1) protein expression in arthritic mice. Furthermore, the phosphoinositide 3­kinase (PI3K)/AKT serine/threonine kinase (Akt) signaling pathway was induced in arthritic mice treated with gambogic acid. The results suggested that gambogic acid induced anti­inflammatory effects in murine collagen­induced arthritis, through the PI3K/Akt signaling pathway, and offers future potential for application in arthritis patients.