Receptor for advanced glycation end products (RAGE) is a receptor of the immunoglobulin super family that plays various important roles under physiological and pathological conditions. Compelling evidence suggests that RAGE acts as both an inflammatory intermediary and a critical inducer of oxidative stress, underlying RAGE-induced Alzheimer-like pathophysiological changes that drive the process of Alzheimer's disease (AD). A critical role of RAGE in AD includes beta-amyloid (Aβ) production and accumulation, the formation of neurofibrillary tangles, failure of synaptic transmission, and neuronal degeneration. The steady-state level of Aβ depends on the balance between production and clearance. RAGE plays an important role in the Aβ clearance. RAGE acts as an important transporter via regulating influx of circulating Aβ into brain, whereas the efflux of brain-derived Aβ into the circulation via BBB is implemented by LRP1. RAGE could be an important contributor to Aβ generation via enhancing the activity of β- and/or γ-secretases and activating inflammatory response and oxidative stress. However, sRAGE-Aβ interactions could inhibit Aβ neurotoxicity and promote Aβ clearance from brain. Meanwhile, RAGE could be a promoting factor for the synaptic dysfunction and neuronal circuit dysfunction which are both the material structure of cognition, and the physiological and pathological basis of cognition. In addition, RAGE could be a trigger for the pathogenesis of Aβ and tau hyper-phosphorylation which both participate in the process of cognitive impairment. Preclinical and clinical studies have supported that RAGE inhibitors could be useful in the treatment of AD. Thus, an effective measure to inhibit RAGE may be a novel drug target in AD.
Background:Published association studies have investigated the correlation between interleukin-8 (IL-8) gene polymorphism –251T>A and susceptibility to Alzheimer's disease (AD); however, the results are conflicting. Thus, we conducted the meta-analysis to reassess the effect of IL-8 gene –251T>A variant on the risk of AD.Methods:Relevant studies regarding this association were electronically searched and identified from the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and the Chinese Biomedicine Database. The odds ratios (ORs) with the corresponding 95% confidence intervals (95% CIs) were pooled to calculate the strength of this association.Results:Nine studies with a total of 1406 cases and 2152 controls were included in the meta-analysis. Overall, a significant association of IL-8 gene –251T>A polymorphism with increased risk of AD was observed in several genetic models (allele, A vs T: OR=1.32, 95%CI=1.16-1.50; homozygous, AA vs TT: OR=1.70, 95%CI=1.21–2.21; heterozygous, TA vs TT: OR=1.37, 95%CI=1.12–1.69; recessive, AA vs TA+TT: OR=1.40, 95%CI=1.12–1.75). Similarly, such association was also revealed both in Asian and European populations in the subgroup analysis by ethnicity.Conclusion:The current study suggested that IL-8 gene polymorphism –251T>A may contribute to the susceptibility to AD.
Introduction Peripherally inserted central catheters (PICC) are a type of deep venipuncture, for which the catheter tip malposition rate is high. Aim To examine the feasibility of preventing catheter tip malposition during PICC placement using an ultrasound-guided finger-pressure method to block the internal jugular vein. Material and methods We conducted a double-blinded randomized controlled trial (RCT) at a tertiary public hospital in Hubei province, China. A total of 600 patients were recruited and randomly allocated to the ultrasound-guided finger compression method (UGFCM) and traditional partial head method (TPHM) group (n = 300/group). Incidence of catheter tip malposition was assessed as the primary outcome of the study. A systematic literature review and meta-analysis was performed. We searched MEDLINE, EMBASE, Cochrane Library, China-National Knowledge Infrastructure, and Chinese Biomedicine Database and performed publication bias and sensitivity analyses on 10 extracted studies. Results There were no significant differences in baseline demographic and clinical characteristics between the two groups (p > 0.05). Overall incidence of catheter tip malposition was significantly lower in the UGFCM and TPHM group (1.67% vs. 10.3%) and particularly the incidence of malposition in the internal jugular vein (1% vs. 9%). In the meta-analysis of 10 eligible studies, with 1263 cases using the UGFCM method while 1261 adopted the TPHM method, the results showed that the incidence of catheter tip malposition was significantly lower in the group using the UGFCM method (OR = 0.17, 95% CI: 0.11–0.27, p < 0.01), which is in line with the results of our RCT study. Conclusions This study may add valuable evidence on adopting the finger-pressure method for blocking neck veins to reduce the incidence of catheter tip malposition, particularly in the internal jugular vein.
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