Objective To study the molecular mechanism of different sensitivities to apoptosis induced by low concentration of As2O3 in PML-RARα negative HL-60 cells and PML-RARα positive NB4 cells. Meth-ods NB4 and HL-60 cells were cultured with As2O3 for 1 to 4 days; cell proliferation were detected by MTT method; the apoptosis was detected by flow cytometry,Bcl-2,Bax and Fas mRNA were determined by RT-PCR. Results The proliferation of NB4 cells was inhibited obviously by As2O3(1.0 μmol/L)with the induction of apoptosis( P <0.05) ,which was accompanied by the down-regulation of Bcl-2 mRNA expression( P <0.05)and the ratio of Bcl-2/Bax(P <0.05), but there was no obvious variation of Bax and Fas expression( P >0.05). Inhibition of proliferation and apoptosis were not obvious in PML-RARα negative HL-60 cells induced by low concentration As2O3 ( P >0.05), and there was no obvious variation of Bcl-2, Bax, Fas mRNA expres-sion or Bcl/Bax ratio( P >0.05). Conclusion The ratio of Bcl-2/Bax is contributed to the different sensitiv-ities of PML-RARα negative HL-60 cells and positive NB4 cells induced by low concentration of As2O3.

Objective:To explore the clinical efficacy of computer-assisted cognitive training in the treatment of cognitive impairment after stroke.Methods:A total of 155 stroke survivors with vascular cognitive impairment were identified at 31 hospitals. They were randomly divided into a control group of 72 and an experimental group of 77 (6 failed to follow up). The control group received 30 minutes of conventional cognition training 5 times a week for 2 weeks, while the experimental group was given computer-assisted cognition training. Before and after the treatment, both groups′ cognition was evaluated using Chinese versions of the Mini Mental State Assessment Scale (MMSE) and the Montreal Cognitive Test (MoCA).Results:After the treatment, the average MMSE and MoCA scores of the observation group [(22.5±3.62) and (19.69±4.43)] and the control group [(21.7±4.30) and (19.10±5.58)] were significantly better than those before the treatment [(19.3±3.08) and (16.79±4.58); (19.7±3.11) and (17.74±5.25)]. The post-treatment difference between the groups′ averages was not significant, but the observation group′s improvements on the immediate memory, delayed memory and calculation portions of the MMSE were significantly greater than those of the control group.Conclusions:Computer-assisted cognition training can improve the overall cognitive functioning of stroke survivors, achieving the same therapeutic effect as conventional cognitive therapy. It is more effective than conventional cognitive therapy in promoting immediate memory, delayed memory and calculation ability.

OBJECTIVETo compare the efficacy and toxicity of the chemotherapeutic regimen containing pirarubicin and mitoxantrone on the treatment of relapsed or refractory acute myeloid leukemia (AML) in adults.

METHODSIn this open prospective multicentre study, we randomly assigned patients with relapsed or refractory AML to receive TAE regimen (pirarubicin+cytarabine+etoposide) versus MAE regimen (mitoxantrone + cytarabine + etoposide). The efficacy and toxicity were compared between the two groups.

RESULTS56 patients entered this clinical trial. The complete remission (CR) rate on TAE arm was 79.0% versus 55.6% on MAE arm with the overall response (OR) rates of 86.8% versus 88.9%, respectively. The CR was higher on TAE arm (P=0.035) but with no significant difference between the two groups regarding the overall response (OR) rate. The regimens were well tolerated in both groups. Hematologic and non-hematologic toxicity were similar except relatively lower the mean dosage of G-CSF, red blood cells and platelets transfusion on TAE arm. No significant differences were seen between the two groups regarding the overall survival and relapse free survival rates.

CONCLUSIONTAE regimen might be an effective salvage therapy in patients with relapsed or refractory AML.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Dactinomycin ; administration & dosage ; Doxorubicin ; administration & dosage ; analogs & derivatives ; Etoposide ; administration & dosage ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Methotrexate ; administration & dosage ; Prospective Studies ; Recurrence ; Remission Induction

Objective:To investigate the role of miRNA-4298/PADI4/p53 signal axis in mediating 4f-induced apoptosis of leukemia cells.Methods:The cell growth density was observed under inverted microscope and the proliferation of leukemia cells was detected by CCK-8 counting assay. The expression of PADI4 and P53 at mRNA level was detected by qRT-PCR. Cell cycle and apoptosis were measured with flow cytometry. The expression of PADI4, P53, Bcl-2, Bax, caspase-3 and caspase-9 at protein level was detected by Western blot. Differential miRNA and mRNA expression profiles was detected by next generation sequencing. Databases such as TargetScan were used to predict the potential upstream and downstream genes of PADI4. A luciferase reporter assay was used to detect the 3′UTR of PADI4 targeted by miRNA-4298. Cell transfection assay was used to detect the effect siRNA, PADI4 vector, miRNA mimics and miRNA inhibitor in interference and rescue.Results:Nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor 4f could inhibit the proliferation of THP-1, K562 and U937 cells, and induce the apoptosis of these leukemia cells. It downregulated the expression of PADI4 mainly through the binding activity of miRNA-4298 to miRNA sponges, which resulted in the proliferation inhibition and apoptosis of leukemia cells. The inhibited proliferation and apoptosis of leukemia cells by 4f were associated with the increase of P53 expression after the decrease of PADI4 expression. The PADI4-dependent upregulation of P53 led to the ratio inversion of downstream Bcl-2/Bax, which activated caspase-3 or caspase-9 to induce the apoptosis of leukemia cells.Conclusions:The apoptosis of leukemia cells induced by Nrf2 inhibitor 4f was mainly associated with the miRNA-4298/PADI4/p53 axis, suggesting that it might be a novel signaling pathway for targeted therapy.

Skin modeling of transdermal drug delivery system refers to experimental models that mimic the structure and function of human skin to explore and evaluate absorption,penetration,and efficacy of medicines in transdermal drug delivery.It provides an alternative to traditional human skin experiments and reduces the use of human skin in medical research,which is convenient,controllable,and cost effective.For skin models of transdermal drug delivery systems,this article introduces commonly used animal skin models,artificial skin models,and recombinant human skin models from the perspective of the transdermal absorption pathway of medicines,and analyzes their advantages,disadvantages,and applications so provide references the research and development of transdermal formulations and topical therapies.