Gene Mutation and Overexpression of Newly Diagnosed Multiple Myeloma Patients / 中国实验血液学杂志

OBJECTIVE@#To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients.@*METHODS@#Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH).@*RESULTS@#Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression.@*CONCLUSION@#There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.

Effect of CDK1 Interferes with the Regulation of PLK1, Aurora B and TRF1 on the Proliferation of Leukemia Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of CDK1 interference regulation of PLK1, Aurora B and TRF1 on the proliferation of leukemia cells.@*METHODS@#The human myelogenous leukemia cell line HL-60 was selected as the research object, and the effect of TRF1 expression and its changes on cell proliferation and cycle was investigated by regulating intracellular CDK1 expression. The objects were divided into 5 groups, including control group, shRNA-NC group, CDK1-shRNA group, pcDNA group and pcDNA-CDK1 group. RT-PCR was used to detect the CDK1 expression of cells in each group; colony formation was used to detect the proliferation of the cells. Western blot was used to detect the expression of CDK1, PLK1, Aurora B, TRF1, and cyclin p53, p27, cyclinA.@*RESULTS@#The phosphorylation level of PLK1, Aurora B and the expression of TRF1 in the CDK1-shRNA group were significantly down-regulated as compared with those in the control group (P<0.05). Compared with the control group, the cells in CDK1-shRNA group showed lower clone formation rate, the increasing of cycle-associated proteins p53 and p27 and the decreasing of cyclinA expression (P<0.05). It was shown that interfered CDK1 expression could inhibit the proliferation of HL-60 cells and prolong the time that they enter mitosis, thereby extending the cell cycle. Compared with the control group, the overexpressed CDK1 in the pcDNA-CDK1 group made the phosphorylation level of PLK1, Aurora B, and TRF1 expression increase significantly (P<0.05), also the colony formation rate (P<0.05). The cycle-related proteins p53 and p27 was down-regulated, while cyclinA expression was up-regulate significantly (P<0.05). The results indicted that overexpressed CDK1 could stimulate adverse reactions, thereby promoting the proliferation of HL-60 cells and shortening the cell cycle.@*CONCLUSION@#Knocking out CDK1 can inhibit the phosphorylation of PLK1 and Aurora B and negatively regulate TRF1, thereby inhibiting the proliferation of leukemia cells.

Adiponectin Receptor Agonist AdipoRon Inhibits the Proliferation of Myeloma Cells via the AMPK/Autophagy Pathway / 中国实验血液学杂志

OBJECTIVE@#To investigate the inhibitory effect of adiponectin receptor agonist AdipoRon on proliferation of myeloma cell lines and its possible mechanism.@*METHODS@#The myeloma cell lines Sp2/0-Ag14 and MPC-11 were treated with different concentration of AdipoRon. The cell proliferation was detected by CCK-8. Western blot was used to determine the protein level of the signaling pathway. RT-PCR was used to quantify the mRNA copy number of adiponectin receptor AdipoR1 and AdipoR2 in the bone marrow cells from 21 patients with multiple myeloma (MM). Twenty-three normal bone marrow samples were served as control.@*RESULTS@#AdipoRon significantly inhibited the proliferation of MM cell lines Sp2/0-Ag14 and MPC-11 in a concentration-dependent and time-dependent manner. Western blot showed that AdipoRon induced an increase of the expression levels of apoptosis-related proteins cleaved caspase-3 and cleaved PARP. AdipoRon upregulated p-AMPK and its downstream p-ACC in MPC-11. In addition, AdipoRon upregulated LC3-II/LC3-I level and down-regulated the protein level of p62. The expression level of AdipoR1 in MM cells was significantly higher than that in normal controls, and the expression level of AdipoR2 in MM cells was significantly lower than that in normal controls.@*CONCLUSION@#Adiponectin receptors are expressed differentially between MM patients and normal subjects. AdipoRon, an adiponectin receptor agonist, can inhibit myeloma cell proliferation and induce apoptosis, and AMPK/autophagy pathway may be one of its mechanisms.

Gene Mutation in Acute Lymphoblastic Leukemia by DNA Sequencing / 中国实验血液学杂志

OBJECTIVE@#To analyze the characteristics of gene mutation in adult ALL and its clinical significance.@*METHODS@#Clinical data of 134 primary adult ALL patients and DNA sequencing results of 16 kinds of gene mutation were collected. The characteristic of gene mutation and clinical significances were statistically analyzed.@*RESULTS@#In 31 cases of 134 ALL cases (23.13%) the gene mutations were detected as follows: 19 cases of 114 B-ALL cases (16.67%), 11 cases of 19 T-ALL cases (57.89%) and 1 case of T/B-ALL. The incidence of T-ALL gene mutation was significantly higher than that of B-ALL (χ@*CONCLUSION@#There may be multiple gene mutations in adult ALL patients. IL7R and NOTCH1 are the most common gene mutations and NOTCH1 mutation may indicate poor prognosis. Detection of gene mutations is helpful to understand the pathogenesis of ALL and evaluate the prognosis of adult ALL patients.

Application of Serum Aminoterminal Pro-brain Natriuretic Peptide and Interleukin-6 Levels in Early Diagnosis and Severity Assessment of Preterm Infants with Respiratory Distress Syndrome / 中国医学科学院学报

Objective To evaluate the value of serum aminoterminal pro-brain natriuretic peptide (NT-proBNP) and interleukin(IL)-6 levels in diagnosis and severity assessment of the preterm infants with respiratory distress syndrome(RDS).Methods Totally 150 preterm infants with RDS who were hospitalized in our center from August 2016 to March 2018 were enrolled in this study as the RDS group. These infants were further divided into grades 1,2,3,and 4 according to chest radiography. In addition,158 preterm infants without RDS hospitalized in our center during the same period were included as the controls (control group). Serum NT-proBNP and IL-6 levels were measured by ELISA on days 1,3,and 7 after birth,and their pulmonary arterial pressure (PAP) was monitored as well.Results Serum NT-proBNP and IL-6 levels in RDS group were significantly higher than those in control group on day 1 (t=-91.04,P=0.000;t=-11.03,P=0.000),day 3 (t=-89.10,P=0.000;t=-9.909,P=0.000),and day 7 (t=-87.91,P=0.000;t=-8.548,P=0.000). There were significant differences in NT-proBNP levels among grades 1,2,3,and 4 on day 1 (F=50.89,P=0.000),day 3 (F=49.16,P=0.000),and day 7 (F=45.45,P=0.000),showing an increasing trend. Serum IL-6 levels showed no significant difference among grades 1,2,3,and 4 on day 1 (F=0.89,P=0.448),day 3 (F=0.76,P=0.518),and day 7 (F=0.85,P=0.469). The PAP of the RDS group on days 1,3,and 7 was (49.3±3.7),(40.1±5.4),and (39.0±2.6)mmHg (1 mmHg=0.133 kPa),which were significantly higher than those of the control group (35.0±2.7)mmHg (t=-90.01,P=0.000),(30.0±3.1)mmHg (t=-81.90,P=0.000),(26.0±3.0)mmHg (t=-88.89,P=0.000). Thus,there was a positive correlation between NT-proBNP and IL-6 levels (r=0.876,P=0.000) and a positive correlation between NT-proBNP and PAP (r=0.916,P=0.000) in preterm infants with RDS.Conclusion Monitoring serum NT-proBN contributes to early diagnosis and disease severity assessment in preterm infants with RDS.

Treatment efficacy of intracoronary microcatheter agents in the patients with no-reflow phenomenon:a Meta analysis / 中国介入心脏病学杂志

Objective To systematically review the effects of intracoronary microcatheter agents in the treatment of patients with no-refl ow phenomenon. Methods Databases including Medline, EMbase, the Cochrane Library, CBM, CNKI, VIP and WanFang Data were searched electronically f rom inception to April 2017 for randomized controlled trials (RCTs) about intracoronary agents for no-reflow phenomenon. Two reviewers independently screened literatures, extracted data and assessed the risk of bias of the studies included. Meta-analysis was then performed using RevMan 5.3 software. Results A total of 8 RCTs involving 424 patients were included. The results of Meta-analysis showed that the microcatheter group had significantly better TIMI flow grade[RR=0.38,95%CI(0.27,0.52), P<0.000 01],TIMI myocardial perf usion grade[RR=0.35,95%CI(0.23,0.55),P<0.000 01],corrected TIMI f rame count[MD=-9.99,95%CI(-13.22,-6.76)P<0.000 01]and hypotension[RR=0.57,95%CI(0.35, 0.90),P=0.02] than those of the guiding catheter group. There was no statistical difference between the two groups in short period major adverse cardiovascular events and left ventricular ejection fraction.Conclusions Current evidence shows that intracoronary microcatheter agents could improve blood flow in patients with no-reflow phenomenon and has good safety. Due to the limited quantity and quality of the included studies, the above conclusion still needs to be verified by carrying out more high-quality RCTs.

Metformin Induces Apoptosis of Human Multiple Myeloma Cell U266 through the Mitochondrial Apoptotic Pathway / 中国实验血液学杂志

<p><b>OBJECTIVE</b>Metformin (Met) can inhibit the proliferation of tumor cells in vitro, its effects on multiple myeloma and action mechanisms have been not yet understood. The purpose of this study was to investigate the effect and molecular mechanism of metformin on human myeloma cells U266.</p><p><b>METHODS</b>U266 cells were treated with different concentration of Met, the MTT was used to detect cell proliferation, the PI staining was used to detect the cell cycle, and the protein expression of BCL-2 family and the release of cytochrome C were assessed by Western blot.</p><p><b>RESULTS</b>Metformin could inhibit the proliferation of U266 cell in a time- and concentration- dependent manner. The U266 cells were arrested in G/G phase after metformin treatment for 48 h, as compared with non-treated U266 cells. The proteins expression of BCL-2 and BCL-XL was down-regulated and the protein expression of BAX was up-regulated. The released of cytochrome C from mitochondria to cytoplasm was increased, and protein splicing of PARP was also enhanced.</p><p><b>CONCLUSION</b>Metformin can inhibit the cell proliferation and induce U266 cell apoptosis through the mitochondrial apoptotic pathway.</p>

Adjuvant effects of Zhenyuan capsule on chronic heart failure: Meta-analysis / 中国中药杂志

To systematically review the adjuvant effects of Zhenyuan capsule on improving the cardiac function of patients with chronic heart failure. Databases including PubMed, EMbase, the Cochrane Library, CBM, CNKI, VIP and Wanfang Data were searched electronically from inception to October 2016 to collect randomized controlled trials (RCTs) about Zhenyuan capsule for adjuvant treatment of chronic heart failure. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, Meta-analysis was performed by using RevMan 5.3 software. A total of 14 RCTs involving 1 204 patients were included. The results of Meta-analysis showed that the Zhenyuan capsule group had significantly better effectiveness in cardiac function (RR=1.27, 95%CI 1.20 to 1.35, P < 0.000 01), stroke volume (WMD=7.62, 95%CI 6.39 to 8.84,P < 0.000 01), scores of HAMA (WMD=-4.16, 95%CI -5.59 to -2.72, P < 0.000 01), psychological effect of HAMA (RR=1.47, 95%CI 1.15 to 1.89, P=0.002), and traditional Chinese medical syndrome (RR=1.46, 95%CI 1.25 to 1.72, P < 0.000 01) than those of the control group, with statistically significant differences. Current evidence showed that Zhenyuan capsule combined with routine treatment could improve the cardiac function and quality of life of patients with chronic heart failure, and with high safety. Due to the limited quantity and quality of the included studies, the above conclusion still needs to be verified by carrying out more high-quality RCTs.