1.Changes of Renal Function in Elderly Patients with Heart Failure but Normal Ejection Fraction and Its Clinical Significance
Wenmin WEN ; Guang SUN ; Xiaoyi ZHANG ; Jie LIN
Journal of China Medical University 2015;(7):618-621
Objective To observe the changes of renal function in elderly patients with heart failure but normal ejection fraction,and explore its clinical significance. Methods A total of 145 cases diagnosed as coronary artery disease from Department of Geriatric Cardiology in The First Affili?ated Hospital of China Medical University were enrolled in the study. All of the cases were divided into HFPEF group(65 cases)and non HFPEF group(80 cases). All patients underwent cardiac ultrasound,BNP and renal function examination,and the glomerular filtration rate(GFR)was cal?culated. Results The average age of patients in HFPEF group was significantly higher than non HFPEF group(P<0.001),and the incidence of hypertension,diabetes,coronary heart disease,atrial fibrillation,or concomitant incidence of two or more kinds of these disease in HFPEF group was significantly higher than non HFPEF group(P1=0.046,P2<0.001,P3=0.002,P4=0.021,P5<0.001);the GFR of two groups of patients were lower than normal level,but the GFR of HFPEF group was significantly lower than non HFPEF group(P=0.046);E/Em was significantly higher (P<0.001),Em was significantly lower(P=0.002),left atrial diameter was significantly higher(P<0.001),LVEF was significantly lower(P=0.012),BNP values were significantly higher(P=0.001)in HFPEF group than in the non?HFPEF group;There were significant linear correlation between GFR and E/Em(r=-0.428,P=0.001),GFR and the BNP(r=-0.435,P=0.001),E/Em and BNP(r=0.392,P=0.002)in HFPEF group. Conclusion Elderly patients with heart failure but normal ejection fraction were older,and more of them were complicated with hyperten?sion,diabetes,coronary heart disease,atrial fibrillation,or concurrency of these diseases. Glomerular filtration rate was significantly decreased in el?derly patients with HFPEF,which has a significant correlation with diastolic function parameters.
2.Regulation of MMP-2 and TIMP-3 expression by uPA signal transduction system in human bone giant cell tumor
Ruobing XU ; Jianming WEN ; Meng ZHANG ; Changhai L ; Gang XIAO ; Wenmin ZHANG ; Huizhen LIANG
Chinese Journal of Pathophysiology 2000;0(11):-
AIM: To study effects of urokinase-type plasminogen activator (uPA) signal transduction on expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) in giant cell tumor of bone (GCT). METHODS: Expression of uPAR, MMP-2 and TIMP-3 in GCT tissue was detected by immunohistochemistry. Phosphorylation level of mitogen-activated protein kinase (p44) in uPA/uPAR signal pathway in cultured GCT cells was detected by immunoprecipitation. The expression of MMP-2 and TIMP-3 in cultured cells after treatment with uPA-ATF or anti-uPAR antibody was also detected by Western blotting. RESULTS: 1) Urokinase-type plasminogen activator receptor (uPAR) was positive on the cell membrane and in cytoplasm of some mononuclear stromal cells (MSCs) and multinucleated giant cells (MGCs); 2) MMP-2 was positive in the cytoplasm and on the cell membrane of almost all of MSCs and some of MGCs. The polar distribution of MMP-2 in the cytoplasm of MGCs was especially obvious; 3) The expression of TIMP-3 of some MSCs and MGCs in GCT was much lower than MMP-2. The positive signal also showed a prominent polarity; 4) After treatment with uPA-ATF, the phosphorylation level of p44 in GCT cultured cells was much higher than the control. Addition of anti-uPAR antibody in the cells remarkably down-regulated the phosphorylation level of p44 as compared with the control group, suggesting that uPA-ATF participates cell signal transduction and this reaction can be inhibited by anti-uPAR antibody; 5) uPA-ATF cell signal pathway up-regulated expression of MMP-2 and TIMP-3, while anti-uPAR antibody down-regulated the expression of MMP-2 and TIMP-3. CONCLUSION: These results demonstrate for the first time that uPA-ATF directly regulates the expression of MMP-2 and TIMP-3 by signal transduction pathway, and the over-expression of MMP-2 and TIMP-3 may play an important role in local osteolysis of GCT. [
3.Role of p38MAPK signaling pathways in the apoptosis of C2C12 myoblast cells subjected to cyclical stretch
Zhen TIAN ; Zhuli YANG ; Wenmin JIA ; Xiao YUAN ; Jing QIU ; Yu DA ; Yanxiao DU ; Jiangbo YU ; Yue ZHANG ; Wen LIU
Chinese Journal of Tissue Engineering Research 2011;15(15):2751-2754
BACKGROUND: Because of complicated physiological environment and difficulty to control experimental conditions, it is difficult to get satisfactory results from in vivo studies of cell mechanics.OBJECTIVE: To study the action and mechanism of p38MAPK signaling pathways on myoblast apoptosis based on successful construction of in vitro mechanical stimulation models.METHODS: The C2C12 cells cultured in vitro were divided into control group and SB203580 treatment group. Cyclic tensile stress was applied on the C2C12 myoblast cells for 0, 6, 12 and 24 hours in each group. The Flexcell Strain Unit-5000T was used to expose C2C12 myoblast cell to an equiaxial cyclic of 15% magnitude and a frequency of 10 cycles/min, each cycle including the 3 s stretch and 3 s relaxation. Hoechst 33258 fluorescent staining and optical microscope were used to detect cell apoptosis. RT-PCR, flow cytometric analysis were used to observe the apoptosis of C2C12 myoblast cells and Western blotting were used to detect the activity of p38MAPK and p-p38MAPK. RESULTS AND CONCLUSION: The optical microscope tested the change in the morphology. Hoechst 33258 staining showed that after treatment with cyclic stress, the cell took the typical appearance of apoptosis with chromatin condensation and apoptotic bodies. RT-PCR and flow cytometry showed that with the extension of time the rate of the apoptosis of C2C12 myoblast cell increased. And cells imposed SB203580 before imposing cyclical tensile stress, the results showed that the apoptosis was markedly affected, and the p-p38MAPK expression declined apparently. These findings demonstrate that p38MAPK signaling pathways in stress mediated into C2C12 myoblast cell apoptosis plays an important role.
4.Compression Properties of Fat Layer under Impact Loading
Ronghua LIU ; Yaoke WEN ; Wenmin YAN ; Zhenyu BAO ; Fangdong DONG ; Junyu ZHOU
Journal of Medical Biomechanics 2022;37(2):E238-E243
Objective To study dynamic compression performance of adipose tissues, so as to further reveal the damage mechanism, and provide references for medical treatment.Methods Based on the improved split Hopkinson pressure bar (SHPB) experimental device, the adipose tissue dynamic compression experiment was conducted. The stress-strain curves of adipose tissues at different strain rates were obtained. Then the numerical model of SHPB was established, and the experimental process was simulated and analyzed. The numerical simulation for penetration process of 32 mm diameter rubber non-lethal projectile into the simulated target in human abdomen was carried out.Results Adipose tissues had a noticeable strain rate effect. The stress-strain curves at two high strain rates were approximately straight lines. The slope was similar, and the elastic modulus was 3.25 MPa, which was about 6 times of that under a quasi-static state. The simulation curves of fat SHPB were consistent with the experimental curves, which verified correctness of the constitutive model. In the process of non-lethal projectile penetrating human abdomen, an annular convex area similar to water wave appeared on skin surface, and the fat layer absorbed about 67% of the impact kinetic energy.Conclusions The experimental data of adipose tissues are very accurate. Numerical simulation can reproduce the penetration process well, and provide references for studying the damaging effect of non-lethal weapons on human body.
5.Interaction Between Bruceoside B and Intestinal Flora and Its Inhibitory Effect on Human Lung Cancer A549 Cells
Lingyu SHI ; Wenmin WANG ; Yulin FENG ; Shilin YANG ; Yang WAN ; Daofeng CHEN ; Quan WEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):160-166
ObjectiveTo explore the interaction between bruceoside B and gut microbiota and the inhibitory activity of its metabolites on human lung cancer A549 cells, and to explore the value of bruceoside B in the treatment of non-small cell lung cancer(NSCLC). MethodBruceoside B was co-incubated with the human gut microbiota under anoxic conditions in vitro, and ultra high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to analyze the metabolic transformation products. Cell counting kit-8(CCK-8) assay was performed to determine the effects of bruceoside B and its metabolites on the proliferation of human lung cancer A549 cells and the half inhibitory concentration(IC50) was calculated. Five healthy male rats were gavaged with bruceoside B(2 mg·kg-1) for 7 days after adaptive feeding. The feces of rats were collected before and after administration. 16S rRNA sequencing was used to assess gut microbiota. ResultBruceoside B was mainly metabolized to brusatol by human gut microbiota, the IC50 of bruceoside B and the conversion product to A549 cells were 1 755.50, 19.57 μmol·L-1, respectively, and the conversion product had a better activity at inhibiting A549 cells proliferation than bruceoside B. Additionally, The results of intestinal flora analysis showed no significant differences in α diversity and β diversity of gut microbiota after administration. In terms of species abundance, at the phylum level, bruceoside B decreased the relative abundance of Actinobacteriota and Proteobacteria, increased the relative abundance of Firmicutes, Patescibacteria and Cyanobacteria. At the genus level, bruceoside B decreased the relative abundance of Staphylococcus, Aerococcus and Psychrobacter, increased the relative abundance of Romboutsia, Lactobacillus, Clostridium sensu stricto 1, Norank-f-norank-o-Clostridia-UCG-014, Turicibacter, Allobaculum and Candidatus Saccharimonas. The results of functional prediction showed that the gut microbiota functional compositions were relatively stable. ConclusionBruceoside B can be deglycosylated by intestinal flora and converted into brusatol, with a significant increase in antitumor activity. The administration of bruceoside B will not cause significant changes in the structure and function of the intestinal flora, resulting in intestinal microecological balance disorders, and the administration appears to be beneficial to the intestinal flora of NSCLC patients.