Objective To evaluate the efficacy and safety of sequential treatment of newly diagnosed de novo acute myeloid leukemia (AML) patients with IA and low-dose HA combined with G-CSF regimens as remission induction therapy.Methods Fifty-seven patients with AML were enrolled,which marrow biopsy was hypocellular or active proliferation on the third day from the end of the first course with IA regimen.32 cases of them received the second course with low-dose HA combined with G-CSF regimen,compared with other 25 cases received the second course with another IA regimen.Clinical manifestations,blood count,blood biochemical parameters and bone marrow smears were measured during the courses.Results In study group,21 of 32 cases reached CR,4 PR,and 11 of 20 cases reached CR,2 PR in control group.Overall remission rate (ORR) was higher in study group than that in control group (78.1％ vs 52.0 ％,P =0.038).Both median duration of agranulocytosis and median time for PLT to reach 50×109/L from the lowest were shorter in study group than those in control group (9.5 d vs 28.0 d,U=32.5,P＜ 0.001; 11 d vs 19 d,U=193.0,P=0.001).Component transfusion,not only RBC but PLT,decreased in study group,compared with control group (8 U vs 16 U,U =206.5,P =0.002; 20 U vs 60 U,U =149,P ＜ 0.001).Median durable time of antibiotic intravenous injection was shorter in study group than that in control group (14 d vs 21 d,U=249.5,P=0.015).Visceral hemorrhage rate reduced in study group,compared with control group (x2 =3.90,P =0.048).Conclusion IA and low-dose HA combined with G-CSF regimens sequential treatment as remission induction therapy for newly diagnosed de novo AML patients is effective and well tolerated.

OBJECTIVEThe relationship between polymorphisms of ALAD and VDR genes and individual susceptibility of lead poisoning was investigated in children highly-exposed to lead.

METHODFour hundred and sixty-nine children were recruited into this study and the blood lead, ZPP, hemoglobin as well as three physical developmental indexes (head circumference, height and weight) were measured. VDR and ALAD gene polymorphisms were analyzed by the methods of PCR-RFLP.

RESULTSThe subjects with ALAD2 allele had higher ZPP level (10.12 micro mol/L vs 12.87 micro mol/L) (P = 0.017). The subjects with B allele has larger head circumference than only with b allele (51.19 cm vs 50.75 cm) (P = 0.028).

CONCLUSIONSIt was suggested that the ALAD gene polymorphism modified the relationship between blood lead and ZPP and the VDR gene variants influenced the skull development in children living under lead-polluted environment. The polymorphism of ALAD and VDR genes might serve as the molecular inherited factors modifying the susceptibility of lead poisoning.

Alleles ; Body Height ; drug effects ; genetics ; Body Weight ; drug effects ; genetics ; Child ; China ; epidemiology ; Environmental Pollution ; adverse effects ; Female ; Gene Frequency ; Genotype ; Humans ; Lead ; adverse effects ; blood ; Lead Poisoning ; epidemiology ; etiology ; genetics ; Male ; Polymorphism, Genetic ; Porphobilinogen Synthase ; genetics ; Receptors, Calcitriol ; genetics

Objective To preliminarily investigate the anti-tumor effects of phytosphingosine(PHS)and the involvement of inducing apoptosis of leukemia cells.Methods Cellular model of leukemia was established in leukemia cell lines K562 and SUP-B15.CCK-8 assay and EdU assay were used to measure the viability and DNA synthesis of K562 and SUP-B15 cells.RNA-seq was carried out to verify the differentially expressed genes(DEGs)after PHS treatment.Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were applied to analyze the involved functions and signaling pathways.Comparative Toxicogenomics Database(CTD)and Discovery Studio software were employed to predict the underlying targets of PHS and molecular docking.Cell apoptosis was detected by flow cytometry,mitochondrial membrane potential was evaluated by JC-1 probe,and protein expression of key molecules was validated by Western blotting.Results PHS inhibited the proliferation of K562 and SUP-B15 cells in a time-and dose-dependent manner.The half-maximal inhibitory concentration(IC50)of K562 cells was 17.67 and 12.52 pmol/L for 24 and 48 h,respectively,and the IC50 value of SUP-B15 cells was 17.58 and 14.86 μmol/L for 24 and 48 h,respectively.PHS treatment at a dose of 20 μmol/L for 48 h resulted in significant inhibition of DNA synthesis.GO enrichment analysis of the K562 cells showed that PHS might be involved in positive regulation of apoptotic process,plasma membrane and its integral components,and protein kinase binding and activity.Reverse predictive analysis showed that BCL-2 protein was the most likely target of PHS.PHS significantly increased the apoptotic rate of leukemia cells(P＜0.05)in a dose-dependent manner,reduced the mitochondrial membrane potential,and down-regulated BCL-2 level(P＜0.05)and up-regulated the levels of Cleaved caspase-3 and Cleaved caspase-9(P＜0.05).Conclusion PHS may inhibit the proliferation of leukemia cells by inducing mitochondria-dependent apoptosis,possibly through PHS and BCL-2 interaction.