BACKGROUND: Hemolysis is an important problem in the design and development of artificial heart pumps. Hemolysis is associated with the shear force of blood cells in the pump and the movement time in the pump. OBJECTIVE: To analyze the relationship between the operating parameters of blood pump (flow rate of blood pump), the structure of blood pump (outlet width of blade) and the shear stress of blood cells in artificial heart pump. METHODS: The basic structure of the centrifugal blood pump was designed according to the velocity coefficient method. The three-dimensional model of the blood pump, mesh division and flow field simulation were established by using CFturbo, ANSYS ICEM and FLUENT software respectively to study the best mesh division method. The results of the numerical simulation corrected the diameter of the impeller outlet to finally obtain an artificial heart pump meeting the needs of the human heart. In order to reduce the shear stress and movement time of blood cells in the heart pump, the optimal design and analysis of the impeller inlet flow rate Q (2, 3, 4, 5, 6, 7 L/min) and the operating parameter blade outlet width b2 (2.0, 2.1, 2.2, 2.3, 2.4, 2.5 mm) of the centrifugal artificial heart pump were designed to reduce the probability of hemolysis. RESULTS AND CONCLUSION: (1) As the flow rate increased, the shear stress of the blood cells in the blood pump gradually increased, and the movement time gradually decreased. As the flow rate increased, the standard hemolysis value in the blood pump gradually decreased, and the damage to the blood cells in the blood pump alleviated. When the flow rate was 7 L/min, the standard hemolysis value in the blood pump was the lowest. (2) With the increase of blade outlet width, the shear stress of the blood in the pump decreased, and the movement time of the blood in the pump increased. When the blade outlet width was 2.0-2.5 mm, the hemolysis value in the blood pump decreased with the increase of the blade outlet width. When the blade outlet width was about 2.5 mm, the hemolysis value in the blood pump was the lowest.

Objective To investigate the role of sodium-glucose cotransporter 1(SGLT1)inhibitor mizagliflozin(MIZA)in autosomal dominant polycystic kidney disease(ADPKD).Methods Western blotting,quantitative polymerase chain reaction(qPCR),and immunofluorescence staining were used to determine the expression and distribution of SGLT1 in kidney tissues of PKD1-/-and PKD1+/+mice,human renal cancer adjacent tissue and ADPKD tissue.Renal cyst lining epithelial cells OX161 and renal tubular epithelial cells UCL93 were treated with MIZA,incubated at 37℃for 24,48,and 72 h,and then were subjected to methyl thiazolyl tetrazolium and colony formation assay to observe cell proliferation.The qPCR method was used to determine the mRNA levels of collagen 1α1,collagen 3α1,and fibronectin 1 in OX161 cells treated with 100 μmol/L MIZA for 48 h.The Madin-Darby canine kidney(MDCK)cell 3D cyst formation assay verified the effect of MIZA on cyst formation.The mRNA-seq technology was used to detect differentially expressed genes between UCL93 cells and OX161 cells,and between OX161 cells and OX161 cells treated with 100 μmol/L MIZA for 48 h,and then the differentially expressed genes were analyzed with Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Results The expression level of SGLT1 was significantly increased in the tissues of ADPKD patients and PKD1-/-mice compared to those in normal kidney tissues(P＜0.05,P＜0.01).Immunofluorescence staining revealed that SGLT1 was mainly expressed in the cystic lining epithelial cells.Additionally,MIZA inhibited the proliferation and fibrosis of polycystic kidney cells in a concentration-and time-dependent manner,and also inhibited cyst formation in 3D formation assay in vitro.The mRNA-seq analysis and KEGG enrichment analysis showed that differentially expressed genes between OX161 cells and OX161 cells cultured in 100 μmol/L MIZA for 48 h were mainly enriched in the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt)and mitogen-activated protein kinase(MAPK)signaling pathways,which were the same as those between OX161 cells and UCL93 cells.Conclusion The SGLT1 inhibitor MIZA may inhibit the proliferation and fibrosis of polycystic kidney cells through signaling pathways such as PI3K-Akt and MAPK,delaying the growth of polycystic kidney,and it is a potential therapeutic target for ADPKD.