ABSTRACT
The lung is one of the most common sites for cancer metastasis. Collagens in the lung provide a permissive microenvironment that supports the colonization and outgrowth of disseminated tumor cells. Therefore, down-regulating the production of collagens may contribute to the inhibition of lung metastasis. It has been suggested that miR-29 exhibits effective anti-fibrotic activity by negatively regulating the expression of collagens. Indeed, our clinical lung tumor data shows that miR-29a-3p expression negatively correlates with collagen I expression in lung tumors and positively correlates with patients' outcomes. However, suitable carriers need to be selected to deliver this therapeutic miRNA to the lungs. In this study, we found that the chemotherapy drug cisplatin facilitated miR-29a-3p accumulation in the exosomes of lung tumor cells, and this type of exosomes exhibited a specific lung-targeting effect and promising collagen down-regulation. To scale up the preparation and simplify the delivery system, we designed a lung-targeting liposomal nanovesicle (by adjusting the molar ratio of DOTAP/cholesterol-miRNAs to 4:1) to carry miR-29a-3p and mimic the exosomes. This liposomal nanovesicle delivery system significantly down-regulated collagen I secretion by lung fibroblasts in vivo, thus alleviating the establishment of a pro-metastatic environment for circulating lung tumor cells.
ABSTRACT
OBJECTIVE:To explore risk factors for the death in HIV/AIDS patients suffering from myelosuppression during highly active antiretroviral therapy(HAART)treatment. METHODS:The historical cohort study method was used to choose 735 in-patients from Nanning Forth People's Hospital during Jan. 2011 to Jul. 2015. Univariate and multivariate Logistic regression analy-sis were used to show the risk factors for the death. RESULTS:Of 735 cases,there were 648 survival cases and 87 dead cases, with mortality of 11.8%. Univariate Logistic analysis showed that:male,elder,higher total bilirubin,lower creatinine clearance, lower CD4+T cell count in baseline,combined more opportunistic infection,combined more myelosuppressive drugs,thrombocyto-penia,lower hemoglobin were the risk factors for the death of HIV patients with myelosuppression in HARRT treatment,while route of HIV infection,HAART treatment A including Zidovudine,weight were the protective factors. Multivariate Logistic regres-sion analysis showed male,elder,higher total bilirubin,lower creatinine clearance,lower CD4+ T cell count in baseline,com-bined more opportunistic infection,combined more myelosuppressive drugs,thrombocytopenia,lower hemoglobin were the risk factors for the death of HIV patients with myelosuppression in HARRT treatment too. CONCLUSIONS:Pertinence treatment and control methods for HIV/AIDS with myelosuppression in HARRT treatment should be taken to reduce the mortality in the future.