Objective To evaluate the therapeutic effects of poly(N-isopropylacrylamide)adriamycin magnetic nanoparticles(ADM-PNIPAM-Fe_3O_4)on liver VX2 tumor in rabbits via transcatheter arterial chemoembolization.Methods VX2 tumor pieces were successfully implanted into liver lobes of rabbits with liver tumors formation.All the animals were randomly divided into 4 groups of 8 each.Group A(control group)injected with 10 ml physiologic saline,Group B(ADM group)treated with free adriamycin (1 mg/kg)via arterial infusion,Group C(ADM-PNIPAM group)ADM-PNIPAM(1.5 mg/kg)was infused through arterial route,Group D(ADM-PNIPAM-Fe_3O_4+M group)ADM-PNIPAM-Fe_3O_4(2 mg/kg)was infused through arterial route;all were in individual doses,respectively;meanwhile an persistant magnet with intensity of 0.4 T was stabilized at the tumor region.Spiral CT scans were performed to measure size of liver tumors and evaluate lung metastasis at 1 day before operation and 14 days after operation.All experimental animals were sacrficed on the 15th days after operation and followed by pathologic and histologic examination of the tumor and lung specimens including changes befor and after the operation with correlative comparisons.Results There were no significant difference in volumes of tumors among 4 groups at 1 day before operation.The average tumor volume in the group A was(23.87?7.02)cm~3 at 14 days after operation;(7.70?1.53)cm3 in group B;(4.29?0.25)cm~3 in group C;(2.05?0.18)cm~3 in group D. The average tumor volumes in the group B,group C and group D were significantly smaller than that in the control group A at same time after operation and there was significant difference among the three experimental groups.According to the order of tumor sizes from small to large was as follows:group D＜group C＜group B＜group A.It showed that the average size of group D(ADM-PNIPAM-Fe_3O_4+M group) was the smallest among the 4 groups.Lung metastatic rates were 100%,66.7%,37.5% and 12.5% in group A,group B,group C and group D at 14 days after operation,respectively.Lung metastatic rates of group D was lower than that of group A,but there were no significant differences among group A,B and C.But pathological examination showed that there were lesser number of lung metastatic tumors in group B and C than that of group A .The intratumoral necrotic degrees showed as group D＞group C＞group B＞group A. Conclusions ADM-PNIPAM-Fe_3O_4 treatment for liver tumor via vascular interventional method combined with magnetic field localized in the lesion possesses significant inhibitory effect on tumor growth of liver VX2 tumor in rabbits.ADM-PNIPAM-Fe_3O_4 is thus initially confirmed as a kind of effective praeputium in interventional chemoembolization.

Objective:To investigate the correlation between Piwi-interacting RNA (piRNA) and diabetic nephropathy (DN).Methods:The differential expression profiles of piRNAs in renal tissues of patients with DN (experimental group) and renal tissues adjacent to tumors of patients with renal tumors (control group) were detected by high-throughput sequencing. The biological function of differentially expressed piRNAs was described by gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis. Real-time fluorescence quantitative PCR was used to detect the serum expression level of target piRNAs in patients with DN. Spearman correlation analysis was used to analyze the correlation between serum target piRNAs and clinical indexes of patients with DN.Results:The results of high throughput sequencing showed that there were 127 differentially expressed piRNAs between DN group and control group, with screening condition of |log 2(fold changes)|≥2 and P<0.05. Among them, there were 99 up-regulated piRNAs and 28 down-regulated piRNAs. The top 5 up-regulated piRNAs were piRNA-hsa-161686, piRNA-hsa-349255, piRNA-hsa-355720, piRNA-hsa-151229 and piRNA-hsa-154959, respectively. The top 5 down-regulated piRNAs were piRNA-hsa-1929960, piRNA-hsa-174194, piRNA-hsa- 148658, piRNA-hsa-172594 and piRNA-hsa-172421, respectively. The PCR verification results of 3 up-regulated genes and 3 down-regulated genes with low P values and high expression levels showed that serum expression level of piRNA-hsa-77976 was significantly down-regulated in patients with DN ( P=0.028), which was consistent with that of sequencing, while the expression levels of other genes were inconsistent with the sequencing results or had no statistical significance. Bioinformatics analysis results predicted that significantly differentially expressed piRNAs might participate in the regulation of DN through Rap1, Ras, PI3K-Akt and axon guiding pathways. The results of correlation analysis showed that the expression level of piRNA-hsa-77976 was negatively correlated with blood urea nitrogen ( r=-0.584, P=0.028), serum creatinine ( r=-0.637, P=0.014), cystatin C ( r=-0.738, P=0.003) and β2 microglobulin ( r=-0.822, P<0.001), and positively correlated with estimated glomerular filtration rate ( r=0.661, P=0.010). Conclusion:The differential expression of piRNA is closely related to DN, and may be used as a new biomarker for the diagnosis and prognosis of DN.