Detection of RAS gene mutation and its clinical significance in children with acute lymphoblastic leukemia / 中国当代儿科杂志

OBJECTIVES@#To investigate the mutation rate of the RAS gene and its clinical significance in children with acute lymphoblastic leukemia.@*METHODS@#A retrospective analysis was performed on the medical data of 120 children with newly diagnosed acute lymphoblastic leukemia, who were admitted to the Third Affiliated Hospital of Zhengzhou University from January 2015 to January 2020 and underwent next-generation sequencing. The clinical and molecular features were analyzed. The impact of RAS gene mutation on the overall survival rate was evaluated in these children.@*RESULTS@#Among the 120 children, 35 (29.2%) had RAS gene mutation, 30 (25.0%) had KRAS gene mutation, and 5 (4.2%) had both NRAS and KRAS gene mutations. All NRAS mutations and 71% (25/35) of KRAS mutations were located at the 12th and 13th codons. RAS gene mutation was detected in 35 (33.3%) out of 105 children with B-lineage acute lymphoblastic leukemia, but it was not detected in those with acute T lymphocyte leukemia. Of all the children, 11 (9.2%) were lost to follow-up, and among the 109 children followed up, 16 (14.7%) died. The children with RAS gene mutation had a significantly lower 2-year overall survival rate than those without RAS gene mutation (P<0.05). The prognosis of children with RAS gene mutation combined with WT1 overexpression and WBC>50×109/L at diagnosis was worse (P<0.05).@*CONCLUSIONS@#RAS gene mutation is commonly observed in children with B-lineage acute lymphoblastic leukemia and may have an adverse effect on prognosis.

Cyanidin-3-glucoside Inhibits Platelet-Derived Chemokines and Their Receptors on Leukocytes of ApoE-/-mice / 中山大学学报(医学科学版)

[Objective]To investigate the effects of different doses of anthocyanins Cy-3-g on serum lipids,platelet-derived chemokines,including MIF and CXCL12 together with their receptors CXCR4 and CXCR7.[Methods]Male ApoE-/-mice were distributed to 5 groups(n=15 per group),and fed with standard diet,high fat diet(HFD),HFD with 200 mg/kg Cy-3-g(low),HFD with 400 mg/kg Cy-3-g(middle),HFD with 800 mg/kg Cy-3-g(high)respectively for 16 weeks. The changes of body weight and food intake were recorded weekly. At the end of the experiment term,the serum lipids(triglyceride,cholesterol,HDL-C,LDL-C)were detected by kits. Arteries were separated to determine plaque histology by Oil-Red-O stain.MIF,CXCL12 and CCL2 in serum were detected by ELISA kits.The expression of CXCR4 and CXCR7 on the surface of leukocytes were tested via flow cytometry. Tail bleeding time was measured mean-while.[Results]Compared with the HFD group,the levels of serum lipids in medium(400 mg/kg)and high(800 mg/kg)Cy-3-g groups were significantly decreased(P<0.05). The plaque area of carotid artery was decreased in high Cy-3-g group(P<0.05).Cy-3-g at all doses significantly reduced the serum concentrations of CXCL12 and CCL2(P<0.002).Cy-3-g of medium(400 mg/kg)and high(800 mg/kg)dose significantly inhibited the expression of CXCR4 and CXCR7 on leukocyte surface(P<0.05). Cy-3-g does not prolong the tail bleeding time.[Conclusions]Anthocyanin Cy-3-g inhibits chemokine CXCL12,CCL2 in serum,and the expression of CXCR4 and CXCR7 on leukocytes without bleeding risk in ApoE-/-mice.

Effect of adenovirus-mediated TXNIP overexpression on apoptosis and injury of H9C2 cardiomyocytes / 生理学报

Adenovirus transfection technique was used in the current study to show if thioredoxin-interacting protein (TXNIP) overexpression can induce cell apoptosis and injury in H9C2 cardiomyocytes cultured in normal glucose condition. And the mechanisms were then investigated. Briefly, H9C2 cardiomyocytes in logarithmic growth phase were randomly divided into three groups: normal cultured group, empty adenovirus vector group (Ad-eGFP) and TXNIP overexpression group (Ad-TXNIP-eGFP). All cells were cultured in DMEM containing normal concentration of glucose (5 mmol/L) and lipid. 72 h after adenovirus transfection, cells and culture mediums were collected for further assay. The results showed that Ad-eGFP and Ad-TXNIP-eGFP adenovirus transfected H9C2 cells successfully, and the transfection efficiency reached the peak at 72 h. Compared with Ad-eGFP group, Ad-TXNIP-eGFP transfection significantly increased TXNIP mRNA (P < 0.05) and protein expression level (P < 0.01). TXNIP overexpression induced remarkable cell apoptosis and injury as evidenced by increased caspase-3 activity (P < 0.05), apoptotic rate (P < 0.01) and LDH activity (P < 0.01). To further analysis the mechanisms of TXNIP-induced cell apoptosis, we also determined Trx activity, Trx related free radical injury and p38 kinase activation, which are involved in free radical induced apoptosis. The results showed that, compared with those in Ad-eGFP group, Trx activity was significantly decreased (P < 0.01), while malondialdehyde (MDA), 3-nitrotyrosine contents and p38 kinase activity were significantly increased (P < 0.01) in TXNIP overexpression group. These results suggest that TXNIP overexpression alone can induce severe apoptosis and injury in H9C2 cardiomyocytes even they are cultured in normal glucose and lipid concentration conditions. The mechanism involved is that overexpressed TXNIP can bind and inhibit Trx, impairs its antioxidative and antiapoptotic function, and then increases free radical induced injury and p38 kinase dependent apoptosis.