No abstract

The prevalence of MCs in patients with DLS was significantly higher than that of patients without DLS. Most of them were type 2 and usually located on the concave side of apex vertebrae. MCs were significantly associated with intervertebral disc degeneration and lumbar scoliosis.

To investigate the expression and biological significance of Leptin, Leptin receptor, Vascular Endothelial Growth Factor (VEGF), and CD34 protein in colorectal carcinoma tissues. The expression of Leptin, Leptin receptor, VEGF, and CD34 was detected in 68 cases of colorectal carcinoma tissues, paired para-carcinoma tissues and normal colorectal tissues by Immunohistochemical SP Method. The results and related clinicopathological data were analyzed. The positive rate of Leptin, Leptin receptor, and VEGF was significantly higher in colorectal carcinoma tissues than that in paired para-carcinoma tissues and normal colorectal tissues. The expression of Leptin, Leptin receptor, and VEGF was correlated with grade of tumor differentiation, depth of bowel wall invasion, lymph node metastasis, Dukes stage, distant metastasis, and lympho/vascular tumor embolization. Microvessel density (MVD) value in colorectal carcinoma was significantly higher than that in para-carcinoma tissues and normal colorectal tissues, and the density in para-carcinoma tissues was higher than that in normal colorectal tissues. The expression of Leptin, Leptin receptor, VEGF, and MVD value in colorectal carcinoma was positively correlated. In conclusion, microvessel density value is an important index of the growth, invasion, and metastasis of colorectal carcinoma. The binding of Leptin and Leptin receptor promotes the proliferation of colorectal carcinoma cells. The synergy between Leptin and VEGF accelerates the angiogenesis in colorectal carcinoma and accelerates the invasion and metastasis of the tumor cells.

No abstract

BackgroundSi-Miao-San (SMS) is a well-known traditional Chinese medicine. This study aims to evaluate the anti-inflammatory effects of SMS on gouty arthritis and its potential mechanism of action.MethodsThe effects and mechanism of SMS were evaluated in monosodium urate (MSU)-treated mice or macrophages. The expression of cytokines and PI3K/Akt was analyzed using real-time PCR and Western blotting analyses. Macrophage polarization was assessed with immunofluorescence assays, real-time PCR, and Western blotting. Mass spectrometry was used to screen the active ingredients of SMS.ResultsPretreatment with SMS ameliorated MSU-induced acute gouty arthritis in mice with increased PI3K/Akt activation and M2 macrophage polarization in the joint tissues. In vitro, SMS treatment significantly inhibited MSU-triggered inflammatory response, increased p-Akt and Arg-1 expression in macrophages, and promoted M2 macrophage polarization. These effects of SMS were inhibited when PI3K/Akt activation was blocked by LY294002 in the macrophages. Moreover, SMS significantly reduced serum uric acid levels in the hyperuricemia mice. Using mass spectrometry, the plant hormones ecdysone and estrone were detected as the potentially effective ingredients of SMS.ConclusionSMS ameliorated MSU-induced gouty arthritis and inhibited hyperuricemia. The anti-inflammatory mechanism of SMS may exert anti-inflammatory effects by promoting M2 polarization via PI3K/Akt signaling. Ecdysone and estrone might be the potentially effective ingredients of SMS. This research may provide evidence for the application of SMS in the treatment of gout.

Background Hyperuricemia and gout have become public health concerns; many important guidelines have recommended xanthine oxidase inhibitors (XOIs) as the first-line urate-lowering therapies (ULTs) to treat chronic gout with hyperuricemia. However, whether treating hyperuricemia and gout with ULTs modifies cardiovascular risks remains controversial. The aim of this study was to assess the incident risk of cardiovascular (CV) events (CVE) in hyperuricemia population, assess the cardiovascular benefit-risk of ULTs in hyperuricemia patients with or without gout in diverse cardiovascular risk sub-groups, and specify the safety of different ULTs. Methods We searched PubMed, Embase, the Cochrane Library, Wanfang, Chongqing VIP (CQVIP, en.cqvip.com), and China National Knowledge Infrastructure Database for prospective cohort studies and randomized controlled trials (RCTs) in English and Chinese. Potential medications included XOIs, and uricosurics. RCTs were divided into sub-groups analysis based on blinding status and patients’ history of CV diseases. Risk ratios (RRs) were calculated and were reported with corresponding 95% confidence intervals (CIs) by fixed-effects or random-effects model. Results Seven prospective cohort studies and 17 RCT studies were included. The risks of both major adverse cardiovascular events (MACE) (RR = 1.72, 95% CI 1.28–2.33) and CVE (RR = 1.35, 95% CI 1.12–1.62) were higher in the hyperuricemia population than non-hyperuricemia one. In seven RCT studies where XOIs were compared with no-treatment or placebo, the results of five low CV risk studies showed that XOIs lowered the risks of both MACE (RR = 0.35, 95% CI 0.20–0.62) and CVE (RR = 0.61, 95% CI 0.44–0.85); whereas two high CV risk studies showed that XOIs lowered the risk of CVE (RR = 0.69, 95% CI 0.54–0.88) rather than MACE (RR = 0.62, 95% CI 0.29–1.35). In nine RCT studies where the cardiovascular safety between febuxostat and allopurinol were compared, no statistical difference was found in the risk of MACE or CVE. Conclusions The hyperuricemia population does have a higher incidence of CVE, and the results suggested that XOIs might reduce the incidence of MACE and total CVE. In addition, from the perspective of cardiovascular safety, febuxostat equaled allopurinol in our meta-analysis.

ObjectiveIncreasing evidence suggests that impaired cartilage is a substantial risk factor for the progression from hyperuricaemia to gout. Since the relationship between cartilage matrix protein and gout flares remains unclear, we investigated its role in monosodium urate (MSU) crystallisation and following inflammation.MethodsBriefly, we screened for cartilage matrix in synovial fluid from gouty arthritis patients with cartilage injuries. After identifying a correlation between crystals and matrix molecules, we conducted image analysis and classification of crystal phenotypes according to their morphology. We then evaluated the differences between the cartilage matrix protein-MSU complex and the pure MSU crystal in their interaction with immune cells and identified the related signalling pathway.ResultsType II collagen (CII) was found to be enriched around MSU crystals in synovial fluid after cartilage injury. Imaging analysis revealed that CII regulated the morphology of single crystals and the alignment of crystal bows in the co-crystalline system, leading to greater phagocytosis and oxidative stress in macrophages. Furthermore, CII upregulated MSU-induced chemokine and proinflammatory cytokine expression in macrophages, thereby promoting the recruitment of leucocytes. Mechanistically, CII enhanced MSU-mediated inflammation by activating the integrin β1(ITGB1)-dependent TLR2/4-NF-κB signal pathway.ConclusionOur study demonstrates that the release of CII and protein-crystal adsorption modifies the crystal profile and promotes the early immune response in MSU-mediated inflammation. These findings open up a new path for understanding the relationship between cartilage injuries and the early immune response in gout flares.

Objective. To evaluate monosodium urate (MSU) crystal deposition and related lesions in the joints of patients with gout and hyperuricemia (HUA) using ultrasound. To explore the association between ultrasound findings and clinical features in gout and HUA. Methods. A total of 202 patients with gout and 43 asymptomatic patients with HUA were included. The clinical data and ultrasonic assessment results were collected and statistically analyzed. Results. Deposition of MSU crystals was found in 25.58% (11/43) of patients with asymptomatic HUA and 76.24% (154/202) of patients with gout. Of the 1,082 joints from patients with gout examined, 33.09% (358/1082) displayed MSU crystal deposition. In the joints with MSU crystal deposition, 77.37% (277/358) had a history of attacks. Among the joints of gouty arthritis, double contour sign (DCS), hyperechoic aggregate (HAG), and tophi were found in 32.65% (159/487), 7.80% (38/487), and 24.64% (120/487) of the joints, respectively. DCS and tophi, but not HAG, increasingly appeared with the extension of gout duration. In patients with more than 15 years of gout history, DCS, Tophi, and HAG were found in 48.18%, 40.00%, and 6.36% of US assessed joints, respectively. In patients with gout, synovial lesion and bone erosion were found in 17.74% (192/1082) and 7.58% (82/1082) of joints, respectively. The synovial lesion was related to HAG, while bone erosion was related to tophi and DCS. Nephrolithiasis was detected in 20.30% (41/202) of patients with gout and 4.65% (2/43) of HUA patients, indicating that nephrolithiasis occurred in more patients with gout than in patients with HUA. Conclusion. HAG is an early performance of MSU crystal deposition in joints of gout and HUA. Both DCS and tophi are risk factors for bone erosion. Early urate-lowering therapy (ULT) should be considered in patients with gout, DCS, or tophi.