Mammalian target of rapamycin(mTOR)locates at the downstream of phosphatidylinositol 3 kinase(PI3K)-protein kinase B(Akt)cell signal transduction pathway. Studies find that the abnormal activa-tion of this pathway is correlated with the endocrine and drug resistance of anti human epidermal growth factor receptor-2(HER-2)target therapy in breast cancer. The combination with mTOR inhibitors based on the past traditional drugs can block the pathway and reflect a favourable application prospect in preventing the develop-ment of resistance and restoring the initial sensitivity on tumor cells. mTOR inhibitors are expected to be the new hope for the treatment of breast cancer.

Objective: To investigate the impact for family history of hypertension on masked hypertension (MH) morbidity with relevant cardiac damage. Methods: Our research included in 3 groups: MH group, n=250 consecutive patients treated in our hospital from 2010-01 to 2015-04, Hypertension group, n=250 and Control group, n=250 subjects with normal blood pressure. The family history of hypertension, general clinical information, routine biochemical indexes and the findings of echocardiography were studied and compared among different groups. Results: ① There were 70 (28%) patients with family history of hypertension in MH group, 87 (34.8%) in Hypertension group and 26 (10.4%) in Control group. The ratio of family history of hypertension in MH group was higher than Control group, P<0.001, while it was similar between MH group and Hypertension group, P>0.05. Logistic regression analysis presented that family history of hypertension and body mass index were positively related to the morbidities of MH (r=1.468, r=0.173) and hypertension (r=1.195, r=0.086). ② Compared with Control group, MH group had increased left ventricular mass index (85.64 ± 17.7) g/m2 vs (80.50 ± 15.53) g/m2 and the maximum blood flow velocity of aortic valve (115.74 ± 16.54) cm/s vs (112.40±14.21) cm/s, all P<0.05. In MH group, compared with those without family history of hypertension, the patients with family history had the higher left ventricular mass index (89.22 ± 19.08) g/m2 vs (84.25 ± 16.99) g/m2 and the maximum blood flow velocity of aortic valve (119.19 ± 14.97) g/m2 vs (114.39 ± 16.96) g/m2, all P<0.05. Conclusion: The subjects with family history of hypertension had the higher risk of MH morbidity with more severe cardiac damage.

We tried to construct and identify the recombinant replication-deficient adenovirus vector coding for human tissue factor pathway inhibitor 2 (hTFPI-2) gene by AdMax system in HEK293 cells. Firstly, we obtained hTFPI-2 gene from the recombinant plasmid pIRES2-EGFP-TFPI-2 by PCR using primers with restriction endonuclease site of EcoRI or SacI. After digesting the hTFPI-2 gene and plasmid PDC316-IRES-EGFP shuttle vector, we ligated them with T4 ligase and formed the recombinant shuttle vector PDC316-IRES-EGFP-hTFPI-2. It was confirmed that the ligation product was inserted the gene of hTFPI-2 correctly by sequencing. Then we took cotransfection of HEK293 cells with the recombinant shuttle vector and genomic plasmid pBHGloxdeltaE1,3Cre by liposome lipofectamine2000, and finished the package of recombinant adenovirus Ad-hTFPI-2. The results of the PCR test and restriction endonuclease digestion confirmed the successful construction of the recombinants Ad-hTFPI-2. Furthermore, we measured the titre of Ad-hTFPI-2 with the aid of green fluorescence protein expression after multiplication and purification. The titre was 0.931 x 10(12) pfu/ml. Finally, we infected U937 monocytes by purified Ad-hTFPI-2, and determined the infection efficiency and the TFPI-2's level and activity. The efficiency of Ad-hTFPI-2 infection in U937 cells was 89.33%. After infected by Ad-hTFPI-2, the TFPI-2's level in supernatant increased about 7 fold. Also the TFPI-2 in supernatant had activities of inhibiting trypsin and plasmin. The recombinant adenovirus with the hTFPI-2 gene was constructed successfully. It will be helpful for the further investigation of its potentiality to be applied in antiatherosclerosis.
Adenoviridae ; genetics ; metabolism ; Defective Viruses ; genetics ; metabolism ; Genetic Vectors ; genetics ; Glycoproteins ; biosynthesis ; genetics ; Humans ; Monocytes ; metabolism ; Recombinant Proteins ; biosynthesis ; genetics ; Transfection ; U937 Cells