ABSTRACT
Fibrosis is one of the key factors that lead to the immune exclusion of solid tumors. Although degradation of fiber is a promising strategy, its application was still bottlenecked by the side effects of causing metastasis, resulting in the failure of immunotherapy. Here, we developed an antimetastatic polymer (HPA) for the delivery of chemo-drug and antifibrotic siPAI-1 to form the nano-permeator. Nano-permeator shrank after protonation and deeply penetrated into the tumor core to down-regulate the expression of PAI-1 for antifibrosis, and further promoted the sustained infiltration and activation of T cells for killing tumor cells. Moreover, metastasis after fiber elimination was prevented by multivalent CXCR4 antagonistic HPA to reduce the attraction of CXCL12 secreted by distant organs. The administration of stroma-alleviated immunotherapy increased the infiltration of CD8+ T cells to 52.5% in tumor tissues, inhibiting nearly 90% metastasis by HPA in distant organs. The nano-permeator reveals the mechanism and correlation between antifibrosis and antimetastasis and was believed to be the optimizing immunotherapy for solid fibrotic tumors.
ABSTRACT
Objective To investigate the prevalence rate of metabolic syndrome (MS) and its related diseases in Bengbu community residents. Methods 3246 residents aged from 25 to 74 years were chosen through cluster random sampling method, including 1459 males and 1787 females. MS and its related diseases were examined. Results (1) The prevalence rate and standardized rate of MS was 20. 5% and 16.0%, respectively, which reached higher level all over China. The prevalence rate of male and female was 22. 9% and 18. 6%, respectively. The highest prevalence rate occurred in presenium patients. (2)The prevalences of various metabolic diseases were increased with aging except for overweigh/obesity and MS (P<0.01). The prevalence of various metabolic diseases was 1 times higher in elderly patients than that in young patients, and the prevalence rate of MS in male and female increased to 2.8 times and 2.7 times, respectively. The prevalence rate of type 2 diabetes mellitus increased biggest, male to 7.9 times and female to 12.8 times compared with the original level. (3) The multiple components clustering rate of MS was high, only 33.8% of individuals had no metabolic disorder. Conclusions The prevalence rates of MS and its related diseases are high in Bengbu community residents. It is necessary to take comprehensive measures to prevent and control MS in community.