Objective:To investigate the expression and clinical application value of exosomal circRPS6 in serum of colorectal cancer (CRC) patients.Methods:Peripheral serum samples were collected from 115 CRC patients admitted to Henan Provincial People′s Hospital from January 2019 to December 2020. There were 68 males and 47 females, aged (63.0±9.5) years. Meanwhile, one hundred and twenty healthy subjects from the same period wereenrolled, with 70 males and 50 females, aged (61.0±10.7) years. In addition, sixty pairs of tumor and adjacent tissue specimens from CRC patients undergoing surgical treatment were collected. The circRPS6 expression in serum exosome and tissue of CRC patients were detected via real-time fluorescence quantitative PCR (RT-qPCR), and its relationship with clinicopathological features and prognosis of CRC patients were also investigated. The levels of CEA and CA19-9 in serum were detected by electrochemiluminescence assay. The ROC curve and AUC were used to estimate the diagnostic capacity. Univariate and multivariate regression analysis was performed using Cox proportional hazard analysis.Results:The expression level of circRPS6 in CRC tissue was significantly higher than that in adjacent tissue( Z=5.38, P<0.001). Compared with healthy control, the expression of serum exosomal circRPS6 was significantly upregulated in the CRC group( t=14.52, P<0.001). ROC curve analysis results showed that the AUC of exosomal circRPS6 was 0.882, which had a higher diagnostic efficacy in CRC patients than CEA and CA19-9 detection. There was a positive correlation between the expression level of exosomal circRPS6 with TNM stage and lymph node metastasis and distant metastasis( P<0.05). Kaplan-Meier survival analysis revealed that CRC patients with low exosomal circRPS6 levels had a much longer average survival time compared with those in high group. Moreover,multivariate analysis results indicated that exosomal circRPS6 was an independent prognostic factor in colorectal cancer. Conclusion:Exosomal circRPS6 is highly expressed in the serum of CRC patients and correlated with malignant progression and poor prognosis, which is expected to be a potential marker for the diagnosis and prognosis evaluation of CRC patients.

Gene therapy represents a promising treatment for the Alzheimer׳s disease (AD). However, gene delivery specific to brain lesions through systemic administration remains big challenge. In our previous work, we have developed an siRNA nanocomplex able to be specifically delivered to the amyloid plaques through surface modification with both CGN peptide for the blood-brain barrier (BBB) penetration and QSH peptide for -amyloid binding. But, whether the as-designed nanocomplex could indeed improve the gene accumulation in the impaired neuron cells and ameliorate AD-associated symptoms remains further study. Herein, we prepared the nanocomplexes with an siRNA against -site amyloid precursor protein-cleaving enzyme 1 (BACE1), the rate-limiting enzyme of A production, as the therapeutic siRNA of AD. The nanocomplexes exhibited high distribution in the A deposits-enriched hippocampus, especially in the neurons near the amyloid plaques after intravenous administration. In APP/PS1 transgenic mice, the nanocomplexes down-regulated BACE1 in both mRNA and protein levels, as well as A and amyloid plaques to the level of wild-type mice. Moreover, the nanocomplexes significantly increased the level of synaptophysin and rescued memory loss of the AD transgenic mice without hematological or histological toxicity. Taken together, this work presented direct evidences that the design of precise gene delivery to the AD lesions markedly improves the therapeutic outcome.