Objective:To evaluate the clinical characters of patients treated with percutaneous coronary intervention based on different age groups d.To provide the evidence for improving primary prevention and secondary prevention of coronary heart disease.Methods:A total of 1 428 CAD patients were enrolled in this study.Blood pressure,blood lipids,blood sugar,smoking and other risk factors of different age groups were compared.And,their drug therapy in hospital were analyzed and compared.Results:1.The proportion of patients less than 60 years old is 47.7%.There were less female patients in young and middle-age groups.2.The proportion of patients with dyslipidemia and diabetes in each age group were low.While,the proportion of patients with hypertension were high.3.There were high proportion of hypertension and diabetes in early-old age and middle old age groups.In the young and middle age groups,the high proportion is on smoking and alcohol taking.4.The control level of blood pressure,blood glucose,CHO were not good.Conclusion:young and middle age patients ranged about 50% of in-hospital patients who received PCI.And the blood pressure,blood glucose,serum cholesterol of most patients were normal.So,in addition to traditional risk factors,the future study should research other risk factors for cardiovascular disease.
The present study aimed to investigate the effect and possible mechanism of recombinant human thrombopoietin (rhTPO) on mouse 32D cells (a mouse myeloid progenitor cell line) treated with serum from patients with aplastic anemia and to elucidate the potential mechanism of rhTPO in the treatment of aplastic anemia. After treatment with aplastic anemia serum, the apoptotic rate of 32D cells was increased and the proliferation of 32D cells was significantly inhibited. rhTPO reduced the apoptotic rate and promoted the proliferation of 32D cells, while rhTPO failed to restore the cell proliferation of 32D cells from aplastic anemia serum group to the normal level as compared to that from the normal serum group. The phosphorylation level of STAT3 protein was higher, and the phosphorylation level of STAT5 protein was lower in 32D cells from aplastic anemia serum group than that in normal serum group. After rhTPO treatment, the phosphorylation level of STAT3 protein in aplastic anemia serum group was decreased and the phosphorylation level of STAT5 protein was increased. The expression levels of Survivin and Bcl-2 were significantly decreased in 32D cells from aplastic anemia serum group, which were significantly increased after rhTPO treatment. The expression level of Bax protein in 32D cells from the normal serum group after rhTPO treatment was significantly decreased; while the mRNA expression level of Bax was not affected by rhTPO. The expression levels of Bax mRNA and protein were significantly up-regulated in 32D cells from aplastic anemia serum group, which was significantly decreased by rhTPO treatment. In conclusion, our results indicated that aplastic anemia serum impaired proliferative potential and enhanced apoptosis of 32D cells. Further mechanistic studies revealed that rhTPO promoted cell proliferation and attenuated apoptosis of aplastic anemia serum-treated 32D cells via activating STAT3/STAT5 signaling pathway and modulating apoptosis-related mediators.
This study was aimed to investigate the quantity and subtypes of dendritic cells (DC) in patients with immune related pancytopenia (IRP) and to explore the role of DC in pathogenesis of IRP. The quantity of plasmacytoid dendritic cells (pDC, Lin(-)HLA-DR(+) CD123(+) cells) and myeloid dendritic cells (mDC, Lin(-)HLA-DR(+) CD11c(+)cells) in peripheral blood of 65 patients with IRP (37 new diagnosed and 28 remitted) and 17 healthy controls were analyzed by flow cytometry. The results indicated that the ratio of pDC in peripheral blood mononuclear cells (PBMNC) was (0.91 ± 064)% in new diagnosed group, which was significantly higher than that in remission group (0.39 ± 0.11)% and control group (0.29 ± 0.13)% (P < 0.01), while this ratio of pDC in remission group was higher than that in control group (P < 0.05). The ratio of mDC in PBMNC was (0.21 ± 0.20)% in new diagnosed group and (0.34 ± 0.21)% in remission group respectively, there was no statistical difference as compared with control group (0.29 ± 0.09)% (P > 0.05). The ratio of pDC to mDC in new diagnosed group was 6.75 ± 7.11, which was significantly higher than that in remission group (1.55 ± 0.93) and control group (1.07 ± 0.43, P < 0.01), there was no statistical difference between the ratio of remission group and control group (P > 0.05). The ratio of pDC in PBMNC of IRP group negatively correlated to ratio of Th1/Th2 (r = -0.347, P < 0.05), and positively correlated to the ratio of auto-antibody on membrane of BMMNC (r = 0.606, P < 0.05) and to the quantity of CD5(+)B cells (r = 0.709, P < 0.05), while it negatively correlated to the levels of hemoglobin (r = -0.381, P < 0.01) and platelets (r = -0.343, P < 0.01). The ratio of mDC in PBMNC positively correlated to the ratio of Th1/Th2 (r = 0.595, P < 0.05) and the level of hemoglobin (r = 0.292, P < 0.05). The ratio of pDC/mDC negatively correlated to ratio of Th1/Th2 (r = -0.395, P < 0.05), it positively correlated to the level of antibody on membrane of BMMNC (r = 0.421, P < 0.05) and the quantity of CD5(+)B cells (r = 0.423, P < 0.05), while it negatively correlated to the levels of hemoglobin (r = -0.304, P < 0.05) and platelets (r = -0.287, P < 0.05). It is concluded that the quantity of pDC in peripheral blood of IRP patients increases, which may be related to the immunopathogenesis of IRP.
In multiple myeloma (MM), bone marrow angiogenesis parallels tumour progression and correlates with disease activity. Recent studies have proved resveratrol possesses antiangiogenic activity in vitro and in vivo. In this study, we examined the effects of resveratrol on myeloma cell dependent angiogenesis and the effects of resveratrol on some important angiogenic factors of RPMI 8226 cells.RPMI 8226 cells were cocultured with human umbilical vein endothelial cells (HUVECs) to evaluate the effects of myeloma cells on angiogenesis. The RPMI 8226 cells were treated with various concentrations of resveratrol (6.25 - 50.00 micromol/L) for different times (12 - 72 hours). Reverse transcriptase polymerase chain reaction (RT-PCR) was used to assay vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), metalloproteinases (MMP)-2 and MMP-9 mRNA. Gelatin zymography was used to analyze MMP-2 and MMP-9 activity. VEGF and bFGF proteins secreted by the cells in the medium were quantified by enzyme linked immunosorbent assay (ELISA).Cell proliferation, migration and differentiation of HUVECs markedly increased by coculture with RPMI 8226 cells. Resveratrol inhibited proliferation, migration and tube formation of HUVECs cocultured with myeloma cells in a dose dependent manner. Treatment of RPMI 8226 cells with resveratrol caused a decrease in MMP-2 and MMP-9 activity. Resveratrol inhibited VEGF and bFGF protein expression in a dose and time dependent manner. Furthermore, decreased levels of VEGF, bFGF, MMP-2 and MMP-9 mRNA from cells treated with various concentrations of resveratrol confirmed its antiangiogenic action at the level of gene expression.Resveratrol inhibits multiple myeloma angiogenesis by regulating expression and secretion of VEGF, bFGF, MMP-2 and MMP-9. Resveratrol may be a potential candidate for the treatment of multiple myeloma.
Multiple myeloma is the second most prevalent type of blood cancer, representing approximately 1% of all cancers and 2% of all cancer deaths. There is therefore a strong need to identify critical targets in multiple myeloma neoplasia and progression. Cancerous inhibitor of PP2A (CIP2A) is a human oncoprotein that regulates cancer cell viability and anchorage-independent growth and induces apoptosis. The present study investigated CIP2A function in the human multiple myeloma cell lines RPMI-8226 and NCI-H929 to determine whether it can serve as a potential therapeutic target. CIP2A was silenced in the cells by transfection of short interfering RNA and cell proliferation and apoptosis were evaluated by a tetrazolium salt-based assay and flow cytometry, respectively. CIP2A knockdown inhibited proliferation and induced apoptosis in RPMI-8226 and NCI-H929 cells and decreased the phosphorylation of phosphoinositide 3-kinase (PI3K) p85, AKT1, and mammalian target of rapamycin (mTOR) without affecting total protein levels. Treatment of CIP2A -depletion cells with insulin-like growth factor 1 decreased the effects of CIP2A inhibition on cell viability and apoptosis. These results indicate that CIP2A modulates myeloma cell proliferation and apoptosis via PI3K/AKT/mTOR signaling and suggest that it can potentially serve as a drug target for the treatment of multiple myeloma.
// Lujun Yang 1, * , Shuangfeng Zhang 1, * , Suraj Konnath George 2 , Rong Teng 1 , Xuefen You 1 , Mengqi Xu 1 , Hong Liu 1 , Xiaoping Sun 3, 4 , Hesham M. Amin 2, 4 , Wenyu Shi 1, 2 1 Department of Hematology, Affiliated Hospital of the University of Nantong, Jiangsu 226001, China 2 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA 3 Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA 4 The University of Texas Graduate School of Biomedical Sciences, Houston, Texas, 77030, USA * These authors have contributed equally to this work Correspondence to: Wenyu Shi, e-mail: shiwenyu@hotmail.com Hesham M. Amin, e-mail: hamin@mdanderson.org Keywords: T-cell lymphoproliferative neoplasms, Notch1, proteasome, γ-secretase inhibitors, bortezomib Received: February 17, 2015 Accepted: March 14, 2015 Published: April 02, 2015 ABSTRACT The T-cell lymphoproliferative neoplasms (T-LPN) are characterized by a poor clinical outcome. Current therapeutics are mostly non-selective and may induce harmful side effects. It has been reported that NOTCH1 activation mutations frequently associate T-LPN. Because anti-Notch1 based therapies such as γ-secretase inhibitors (GSI) are less efficient and induce considerable side effects, we hypothesized that combining low concentrations of GSI and the proteasome inhibitor bortezomib (BTZ) may provide an effective and tolerable approach to treat T-LPN. Hence, we analyzed the in vitro and in vivo effects of GSI-I and BTZ, alone or in combination, against T-LPN. GSI-I and BTZ synergistically decreased cell viability, proliferation, and colony formation, and induced apoptosis in T-LPN cell lines. Furthermore, combining GSI-I and BTZ decreased the viability of primary T-LPN cells from patients. These effects were accompanied by deregulation of Notch1, AKT, ERK, JNK, p38 MAPK, and NF-κB survival pathways. Moreover, combination treatment inhibited T-LPN tumor growth in nude mice. In all experiments, combining low concentrations of GSI-I and BTZ was superior to using a single agent. Our data support that a synergistic antitumor activity exists between GSI-I and BTZ, and provide a rationale for successful utilization of dual Notch1 and proteasome inhibition to treat T-LPN.
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