Relationship between TET2 Gene SNP rs3733609 C/T and JAK2V617F Allele Burden in Patients with Myeloproliferative Neoplasms / 中国实验血液学杂志

OBJECTIVE@#To investigate the relationship between the polymorphism of TET2 gene SNP rs3733609 and JAK2V617F allele burden in patients with myeloproliferative neoplasms (MPN).@*METHODS@#The exon 9 of TET2 gene was amplified by RT-PCR, and the nucleotide sequence of SNP rs3733609 site was analyzed by gene sequencing. The MGB Taqman probe PCR method was used to detect the JAK2V617F allele burden. The correlation of TET2 gene SNP rs3733609 C/T with the JAK2V617F allele burden and clinical parameters was analyzed.@*RESULTS@#TET2 gene rs3733609 C/T heterozygosity (normal T/T) could be detected in 19 cases of 85 cases of JAK2V617F positive MPN (22.4%) patients, while the TET2 gene rs3733609 C/T heterozygosity could be detected only in 9 of the 106 healthy volunteers, and the incidence was only 8.5% (9/106). Compared with the negative group (TET2 rs3733609 T/T), there was no significant difference in the median age, hemoglobin level and platelet count in the patients with TET2 gene SNP rs3733609 (CT/TC) positive, but the WBC count of peripheral blood and JAK2V617F allele burden significantly increased. In JAK2V617F high allele burden group, TET2 gene SNP rs3733609 was positive in 7 cases (36.8%, 7/19), the ratio was higher than that in the low allele burden group(18.2%, 12/66).@*CONCLUSION@#TET2 SNP rs3733609 C/T may be a new susceptible allelee, which affects the clinical characteristics and clonal evolution of MPN patients.

Expression of Aurora Family Genes in Acute Leukemia and Its Clinical Significance / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the mRNA expression of Aurora-A,B,C(AUR-A,B,C) in acute leukemia(AL) and their correlations with the clinical indications.</p><p><b>METHODS</b>The mRNA expression levels of AUR-A,B,C in 73 cases of newly diagnosed AL (untreated group), 20 cases of AL with remission (remission group) and 14 healthy volunteers as control (healthy group) were detected by QRT-PCR, and the difference of expression levels in difference groups, their correlations with clinical indicators and the correlation between the AUR-A,B,C mRNA expression levels themselves were analyzed.</p><p><b>RESULTS</b>The mRNA expression levels of AUR-A,B,C in untreated group were all higher than those in healthy group and remission group(P<0.01), but there was not significant difference between healthy group and remission group(P>0.05); the mRNA expressions of AUR-A,B,C in acute lymphoblastic leukemia(ALL) group were all significantly higher than that in AML group(P<0.01). The mRNA expression of AUR-A,B,C in high risk group was higher than that in low risk group(P<0.05), but there was no difference in mRNA expression of AUR-A,B,C between high risk group and middle risk group as well as between middle risk group and low risk group(P>0.05). The mRNA expression of AUR-A, B, C in CD34, CD71 and CD56 negative group was not statistically different from that in CD34,CD71 and CD56 positive group(P>0.05). In 73 cases of newly diagnosed AL, the mRNA expression levels of AUR-A, B significantly were positively correlated with lactate dehydrogenase(LDH) level and risk stratification (r=0.279, P=0.017; r=0.314, P=0.007 and r=0.277, P=0.018; r=0.349, P=0.002), while the mRNA expression levels of AUR-A, B were not significantly correlated with age, WBC count, blast ratio in bone marrow at initial diagnosis and remission or no-remission after 1 cours of chemotherapy; the mRNA expression level of AUR-C was significantly positively correlated with WBC count (r=0.263, P=0.025), and LDH level (r=0.348, P=0.003) at initial diagnosis and risk stratificantion(r=0.376, P=0.001), and negatively correlated with age (r=-0.241, P=0.040), and was not significantly correlated with blast ratio in bone marrow at initial diagnosis and remission or noremission after 1 course of chemotherapy. There were significant positive correlations in the mRNA expression between AUR-A and B (r=0.444, P=0.000), AUR-B and C (r=0.763, P=0.000) as well as AUR-A and C (r=0.616, P=0.000).</p><p><b>CONCLUSION</b>Aur-A, B, C mRNA were highly expressed in patients with newly diagnosed AL, moreover the mRNA expression levels of Aur-A,B,C were positively correlated with each other, the high expression of Aur-A, B, C are associated with leukemia types, risk stratification, WBC count and LDH level at initial diagnosis, so they all maybe used as the prognostic markers and potential therapeutic targets.</p>

Dynamic changes in PD-1, TLR3, and TLR4 surface expression on peripheral blood mononuclear cells in chronic hepatitis C patients undergoing peg-IFNalpha-2a plus ribavirin combination therapy / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the dynamic changes in expression of programmed death (PD)-1, Toll-like receptor (TLR)3, and TLR4 on the surface of peripheral blood mononuclear cells (PBMCs) in patients with chronic hepatitis C (CHC) that occur in response to pegylated-interferon alpha-2a (peg-IFNalpha-2a) plus ribavirin (RBV) combination therapy, and to analyze the relation to achievement of sustained virological response (SVR). METHODS Twenty-three CHC patients and 10 healthy controls were enrolled in the study. All CHC patients underwent 48 weeks of combination therapy with peg-IFNalpha-2a (180 microg, subcutaneous injection, once weekly) plus RBV (15 microg/kg, oral, once daily). Total PBMCs were isolated from both groups (CHC patients at treatment week 0, 12, 24, and 48 and post-treatment week 24; controls at enrollment) and subjected to flow cytometric analysis of PD-1, TLR3, and TLR4 surface expression. In addition, serum levels of alanine aminotransferase (ALT) and hepatitis C virus (HCV) RNA levels were analyzed by enzymatic assay and the AmpliPrep/COBAS (Roche) nucleic acid amplification test, respectively. SVR was defined as undetectable levels of HCV RNA at post-treatment week 24. Intergroup differences were assessed by one-way ANOVA.</p><p><b>RESULTS</b>The expression ratios of PD-1, TLR4 and PD-1: TLR4 on PBMCs were significantly higher in CHC patients before therapy than in the healthy controls (45.20 +/- 7.12% vs. 16.82 +/- 4.13%, 58.45 +/- 15.13% vs. 21.09 +/- 2.89%, and 35.54 +/- 7.69% vs. 14.12 +/- 2.89%; all P < 0.05). In contrast, the expression ratios of TLR3 and PD-1:TLR3 were slightly, but not significantly, higher in CHC patients before therapy than in the healthy controls (P > 0.05). During the course of peg-IFNalpha-2a plus RBV combination therapy, the expression ratios of PD-1 and TLR4 on PBMCs showed a decreasing trend, while TLR3 expression showed an increasing trend. Furthermore, CHB patients who achieved SVR at post-treatment week 24 had a significantly different expression ratio of PD-1 and TLR3 than those who did not achieve SVR (P < 0.05).</p><p><b>CONCLUSION</b>Surface expression of PD-1, TLR4, and PD-1:TLR4 is up-regulated in the total PBMCs of CHC patients. Peg-IFNalpha-2a plus RBV treatment-induced suppression of HCV replication results in a significant reduction in PD-1 and TLR4 expression on the surface of PBMCs, but a remarkably elevated level of TLR3 expression. The dynamic change in PD-1 and TLR3 expression on PBMCs that occurs during antiviral therapy may be related to achievement of SVR.</p>

A structural equation model for the WHO health survey data / 中华预防医学杂志

<p><b>OBJECTIVE</b>Based on the 2002 WHO health survey data, to explore the latent relationship among self-reported health level, the actual level of health, the social demographic characteristics and the risk factors, and to analyze the influence of the various surveillance indicators on self-reported health and the degree that the self-reported health explained the actual level of health.</p><p><b>METHODS</b>Field tests for various components of the World health survey were conducted in nine countries during 2002, including India, Brazil, Burkina, Hungary, Nepal, Russia, Spain, Tunisia, and Vietnam (29 971). The survey questionnaire included a self-assessment component and anchoring vignette component. The self-assessment component data was adjusted and eliminated the affect of "cut-point bias" by using the anchoring vignette component data, and then was used to build the structural equation model on the relationship among self-reported health level, actual health level, social demographic characteristics and the risk factors.</p><p><b>RESULTS</b>In the final structural equation model, "the actual level of health" = 0.80 × "the self-reported health level" + (-0.04) × "the social demographic characteristics" + (-0.08) × "the risk factors" (R(2) = 0.66), and "the self-reported health level" = (-0.70) × "the social demographic characteristics" + 0.10 × "the risk factors" (R(2) = 0.55). The standardized total effect of self-reported health to the actual level of health was 0.80, and that of the social demographic characteristics to the self-reported health and the actual level of health were -0.70 and -0.60, respectively. And the 16 items of self-reported health consisted of 8 dimensions; and sorted by the power of impact to the actual health level, they were mobility, pain and discomfort, sleep, cognition, feelings, self-care ability, visual capacity and interpersonal activities.</p><p><b>CONCLUSION</b>There were significant linear correlation relationship between the actual level of health and the self-reported health, as well as between the self-reported health and the social demographic characteristics. And the self-reported 16 items used by the 2002 WHO health survey played an important role in the health evaluation of population.</p>

Synthesis of 5-aryl-4-cyano-1H-1, 2, 3-triazoles and biological evaluation of their inhibitory action on tyrosine kinase / 药学学报

5-Aryl-4-cyano-1H-1, 2, 3-triazoles bearing a variety of substituting groups on 5-phenyl were synthesized. Their structures were established by MS, IR and 1H NMR spectra. The crystal structures of compounds 3f and 3m were determined by X-ray diffraction analysis. The active H of the triazole was on 1-N from the crystal structures. The compounds, designed as HER2 tyrosine kinase inhibitors, were screened for bioactivity of growth-inhibition of breast cancer MDA-MB-453 cells. The lowest IC50 value of inhibiting HER2 tyrosine kinase phosphorylation in breast cancer cells is 6.6 micromol x L(-1). The inhibiting-growth of breast cancer cells was enhanced from electron-drawing groups joining 5-phenyl on the triazole.

Isolation, incubation and differentiation of pancreatic islet-derived progenitor cells from newborn SD rats / 中国应用生理学杂志

<p><b>AIM</b>To isolate, culture pancreatic progenitor cells derived from islets of newborn rats, and to observe the effect of GLP-1 (7-36) NH2 on islet progenitor differentiation.</p><p><b>METHODS</b>Islets were isolated purified, islet progenitor cells were isolated and proliferated in the modified RPMI-1640 medium supplemented with 20 microg/L bFGF and 20 microg/L EGF, then were differentiated with 20 nmol/L GLP-1 (7-36) NH2. The properties of islet progenitor cells were identified primarily by hybridization in situ, immunocytochemistry, dithizone (DTZ)-staining, and radioimmunoassay before and after differentiation.</p><p><b>RESULTS</b>Islet progenitor cells did not express PDX-1, insulin and somatostatin, but nestin. After differentiation, a portion of cells expressing PDX-1, insulin mRNA, insulin, somatostatin, and nestin, islet-like cell clusters (ICCs) were formed, DTZ-stained cells were in peripheral region of it. Insulin release was markedly greater in media harvested after differentiation of 3 weeks.</p><p><b>CONCLUSION</b>A kind of progenitor cells exists in pancreatic islet of newborn SD rats, could be expanded continuously. GLP-1 (7-36) NH2 could differentiate pancreatic islet-derived progenitor cells to form ICCs capable of insulin secretion.</p>