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The interaction of advanced glycation end-products (AGEs) with their receptor (RAGE) elicits oxidative stress and inflammation, which is involved in the development of breast cancer. However, large-scale population-based evidence exploring genetically modified circulating levels of AGEs-RAGE axis with risk and mortality of breast cancer is scarce. We recruited 1051 pairs of age-matched breast cancers and controls and measured plasma AGEs and sRAGE concentrations by enzyme-linked immunosorbent assay (ELISA). Multivariate logistic regression and Cox proportional hazard model were used to calculate the effects of plasma levels and genetic variants of the AGEs-RAGE axis and their combined effects on breast cancer risk and prognosis, respectively. Furthermore, linear regression was performed to assess the modifications in plasma AGEs/sRAGE levels by genetic predisposition. Higher levels of AGEs and AGEs/sRAGE-ratio were associated with an increased risk of breast cancer, but sRAGE levels were negatively associated with breast cancer risk, especially in women <60 years. We also observed a positive association between AGEs and the bad prognosis of breast cancer. Although we did not observe a significant contribution of genetic variants to breast cancer risk, rs2070600 and rs1800624 in the AGER gene were dose-dependently correlated with sRAGE levels. Further, compared to the haplotype CT at the lowest quartile of AGEs, haplotypes TT and TA were prominently associated with breast cancer risk in the highest quartile of AGEs. This study depicted a significant association between circulating levels of AGEs-RAGE axis and breast cancer risk and mortality and revealed the potential of plasma AGEs, especially coupled with AGER polymorphism as biomarkers of breast cancer.

Albumin-based hydrogels have emerged as promising nanoparticle systems for the effective delivery of hydrophobic anticancer drugs. Anti-cancer drugs often cause some adverse effects, such as toxicity and rapid clearance by mononuclear phagocytic systems. Herein, a new strategy of synthesizing N-hydroxysuccinimide (NHS)-activated linker to form crosslinkable albumin-based hydrogels (CABH) is reported. The CABH favored physiochemical characteristics improvement of doxorubicin (Dox) and drug release. The CABH was constructed depending on the crosslinking reaction between NHS activated glycerol and albumin. The size of CABH was approximately 200 nm examined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). It was found that the particle size and size distribution of the CABH remained stable in neutral PBS for 1 week. Dox loaded CABH would be controllably released in weak acidic environment verified by in vitro release and in vitro cell imaging. The Dox loaded hydrogel results in significant killing in the case of acidic culture medium. Our work provides a crosslinking method to formulate albumin nanoplatform and improve the size, stability, drug loading capacity and controlled release, which throws light on the potential application in drug delivery.

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Background and aims Risk stratification to identify patients with high risk of variceal rebleeding is particularly important in patients with decompensated cirrhosis. In clinical practice, eliminating gastroesphageal varices thoroughly after sequential endoscopic treatment reduces the rebleeding rate, however, no simple method has been build to predict high risk of variceal rebleeding. We conducted this study to explore the value of the number of endoscopic sessions required to eradicate gastroesphageal varices in identifying high risk of rebleeding. Patients and methods Consecutive cirrhotic patients received sequential endoscopic therapy between January 2015 and March 2020 were enrolled. Endoscopic treatment was performed every 1–4 weeks until the eradication of varices. The primary endpoint was variceal rebleeding. Results A total of 146 patients were included of which 60 patients received standard therapy and 86 patients underwent sequential endoscopic treatment alone. The cut-off value of the number of sequential endoscopic sessions is 3.5 times. Variceal rebleeding was significant higher in patients with endoscopic sessions > 3 times versus ≤ 3 times (61.5% vs. 17.5%, p < 0.001). Variceal rebleeding of patients with endoscopic sessions ≤ 3 times was significant lower than patients with > 3 times in group of standard therapy (19.6% vs. 88.9%, p < 0.001) and endoscopic therapy (15.9% vs. 47.1%, p = 0.028) respectively. Conclusion The number of sequential endoscopic sessions required to eradicate the varices is related to the risk of variceal rebleeding in patients with cirrhosis. If three times of endoscopic treatment can not eradicate the varices, a more aggressive treatment such as TIPS should be seriously considered.