Objective To explore the expression of thioredoxin reductase (TrxR) mRNA and protein,as well as the relationship between TrxR and myeloid leukemia.Methods Bone marrow samples from 20 acute myeloid leukemia (AML),20 chronic myeloid leukemia (CML),and 20 healthy persons as normal control group were collected.The human non small cell lung cancer A549 cells were selected as the positive control group.The expression of TrxR mRNA was detected by real-time quantitative polymerase chain reaction.The expression of TrxR protein level was detected by Western blot.Results The relative quantitation expressions of TrxR mRNA were 6.751 (13.459),4.321 (11.389),18.477 (2.089),1.045 (0.467) in AML,CML,positive control and normal control group,were 17.814±3.979 and 4.860±1.550 in the primary diagnosed/relapse group and complete remission (CR) group of AML patients,and were 19.552 (5.758) and 3.459 (2.047) in the primary diagnosed and treatment group of CML patients.The expression levels of TrxR mRNA in AML,CML and positive control group were significantly higher than that in normal control group (H =43.978,P ＜ 0.001).For AML patients,the expression levels of TrxR mRNA in the primary diagnosed/relapse group,CR,positive control group were significantly higher than that in normal control group (F=246.793,P ＜ 0.001),and the difference between the primary diagnosed/relapse group and positive control group was no significant (P ＞ 0.05).The expression of TrxR mRNA were higher in the primary diagnosed/relapse group than that in CR group,and that in CR group than that in normal control group (both P ＜ 0.05).For CML patients,the expression levels of TrxR mRNA in the primary diagnosed,treatment,positive control group were significantly higher than that in normal controls (H =38.222,P ＜ 0.001),the difference between that in the primary diagnosed and that in positive control group was no significant difference (P ＞ 0.05),but the expression of TrxR were significantly higher in the primary diagnosed group than that in treatment group,and that in treatment group than that in normal controls (both P ＜ 0.05).The expression of TrxR mRNA in the primary diagnosed/relapse group of AML and the primary diagnosed group of CML showed no significant difference (P ＞ 0.05).The positive levels of TrxR protein were 0.679,0.606,0.877 and 0.095 in AML,CML,positive control and normal control group.TrxR protein was highly expressed in myeloid leukemia patients.Conclusion The expression levels of TrxR mRNA and protein are increased in myeloid leukemia.The low expression of TrxR in normal hematopoietic stem cells is highly expressed in myeloid leukemia,and is downgraded after treatment,which may be used as one of the parameters to diagnosis,effect and prognosis of myeloid leukemia.

ObjectiveTo induce monocyte-derived dendritic cells(MoDC)from acute myeloid leukemia (AML) and healthy persons by rhCD40L in normal human AB serum system in vitro and to identify the morphology and phenotype of MoDC. MethodsPeripheral blood mononuclear cells(PBMNC)of AML and healthy persons were cultured in RPMI 1640 media including human AB serum, GM-CSF, rhIL-4 and rhCD40L, respectively. MoDC were identified by morphological features, surface antigen expression and the ability to stimulate T cells. ResultsAfter cultured for 7 days, MoDC displayed typical morphology with elongated dendritic process,and upregulation of the costimulatory molecules CD40,CD80,CD86 and CD83.The morphology and expression of costimulatory molecules were not significantly different between AML and healthy persons (P＞0.05),but were significantly different between rhCD40L group and without rhCD40L group (P＜0.05). MoDC had the ability to activate T cells, and there were no statistical differences between AML and healthy persons(P ＞0.05), but were significant differences between rhCD40L group and without rhCD40L group (P＜0.05). MoDC started to secrete IL-12 on day 5, and there was no statistical differences between AML and healthy persons(P＞0.05),and had differences between rhCD40L group and without rhCD40L group (P＜0.05).ConclusionMoDC can be cultured from the peripheral blood of AML and healthy persons.There were no significant differences in morphology and phenotype.Monocyted-derived DC can be used as an alternative to generate leukemia-specific cytotoxic T cells,especially in the presence of rhCD40L.

Objective To investigate the expression of nuclear factor erythroid-2 related factor 2 (Nrf2) gene in chronic myeloid leukemia (CML) and explore its relationship with clinical characteristics and thioredoxin reductase (TrxR).Methods The expressions of Nrf2 and TrxR genes in bone marrow cells and K562 cells were analyzed in 30 bone marrow preparations of CML patients in different phases,including 20 in chronic phase,3 in accelerated phase,7 in blastic phase by real-time quantitative polymerase chain reaction.Ten health subjects were served as normal controls.Results The relative quantitation expression of Nrf2 and TrxR mRNA were 5.601±1.069 and 9.017±2.398 in chronic phase,1.698±0.349 and 5.590±1.015 in accelerated phase,1.252±0.807 and 5.050±1.469 in blastic phase,1.377± 0.344 and 1.867±0.977 in normal controls.The expressions of both Nrf2 and TrxR mRNA in CML had significant differences from those of the normal controls (x2 =14.680,P =0.002,x2 =8.271,P =0.041).The expression of Nrf2 mRNA in accelerated phase,blastic phase group showed no significant difference (Z =0.011,P =0.496),but lower than that in chronic phase group (Z =2.155,P =0.016,Z =2.534,P =0.006).The difference between the first visit and post-treated group was significant (Z =2.015,P =0.022).The expression in K562 cells and normal controls had significant difference (Z =1.898,P =0.029).In CML patients,the expression of Nrf2 was positively correlated with that of TrxR (r =0.738,P =0.037).Conclusion The expression of Nrf2 gene is higher in the first visit group of CML than that in the other groups,and is decreased after therapy,which may be the molecular marker predicting the progress of CML.Nrf2 mRNA expression level is correlated with TrxR.

Objective:To investigate the differences in dosimetric impacts of the systematic errors induced by the leaf positions of a multi-leaf collimator (MLC) on the volumetric modulated arc therapy (VMAT) for patients with different T stages of nasopharyngeal carcinoma (NPC).Methods:A total of 44 patients with T 1-4N 1M 0 NPC were selected to design the VMAT plans using the Pinnacle planning system as the initial plans. The prescribed doses to the primary gross tumor volume (PGTV) were 68-70 Gy in 33 fractions for patients with T 1 and T 2 stage NPC and 71 Gy in 33 fractions for patients with T 3 and T 4 stage NPC. The prescribed doses to other target volumes were identical. In the initial plan files, a systematic error ranging from ±0.2 to ±1 mm was introduced to the position of each MLC leaf, leading to an increase or decrease in the subfield area. Then, potential error plans at the positions of MLC leaves during VMAT treatment were simulated. Dose evaluation indices involved target volumes and organs at risk (OARs). The indices related to target volumes consisted of the D98% of PGTV and PGTVnd, while those concerning OARs included the D0.1 cm 3 of the brainstem, spinal cord, and optic chiasm. Results:After the systematic errors induced by the positions of MLC leaves were introduced, the sensitivity range of each dose index range was (3.87%-9.87%)/mm ( R2 = 0.932-0.998, P < 0.01). Specifically, patients with stage T 4 NPC displayed higher sensitivity to the D98% of PGTV than those with stage T 1, T 2 and T 3 NPC ( Z = -3.12, -2.86, -2.59, P < 0.05), patients with stage T 3 NPC exhibited lower sensitivity to the D0.1 cm 3 of optic chiasm than those with stage T 1 and T 2 NPC ( Z = -2.92, -2.72, P < 0.05), and patients with stage T 4 NPC manifested lower sensitivity to the D0.1 cm 3 of chiasma than those with stage T 1 and T 2 NPC ( Z = -3.51, -3.25, P < 0.05). The relationship between the sensitivity of MU/Gy and PGTV D98% was y=-3.020+ 0.025 x ( r = 0.80, P < 0.05). Conclusion:The MU/Gy in the plans increased with the T stage of NPC, and the D98% of PGTV was more significantly affected by the systematic errors induced by the positions of MLC leaves. After the systematic errors induced by the positions of MLC leaves were introduced into the VMAT plans, doses to patients with T 4 stage NPC changed more significantly than those to patients with other T stages of NPC. Therefore, stricter quality control of leaf positions is required for patients with T 4 stage NPC, and it is recommended that the systematic errors should be less than 0.42 mm.

Objective: To investigate the inhibitory effect of AKR1B10 inhibitor combined with sorafenib on hepatocellular carcinoma (HCC) xenograft growth. Methods: HepG2 xenograft model was established in nude mice. The mice were then randomly divided into four groups: control group, epalrestat monotherapy group, sorafenib monotherapy group and combination treatment group. Tumor volume, tumor weight, T/C ratio and the change in body weight of nude mice in each group were compared to evaluate the curative effect. Immunohistochemistry staining was used to detect the expression of Ki-67 in tumor tissues to evaluate the proliferation status of tumor cells. One-way analysis of variance was used to compare the differences between the groups. Student’s t-test was used to test means of two groups and chi-square test was used for multiple samples. Results: The differences of the grafted tumor volume before and after treatment between the control group, epalrestat group, sorafenib group and combined therapy group was 238.940 ± 39.813, 124.991 ± 84.670, -26.111 ± 11.518, and -54.072 ± 17.673(mm³), respectively, (F = 37.048, P < 0.001). The tumor mass were 0.273 ± 0.140, 0.158 ± 0.078, 0.079 ± 0.054, 0.045 ± 0.024 (g), (F = 16.594, P < 0.001); T/C ratio were 100%, 57.9%, 28.9%, 16.5%, and Ki-67 positive rate were 23.295 ± 6.218, 13.503 ± 3.392, 7.325 ± 2.257, 4.664 ± 1.189 (%), (χ² = 822.203, P < 0.001) . The tumor volume (t = -3.579, P = 0.002) and Ki-67 positive rate (t = -10.003, P < 0.001) in epalrestat monotherapy group were significantly lower than control group. The tumor volume (t = 2.056, P = 0.025), tumor mass (t = 2.101, P = 0.043), and Ki-67 positive rate (t = -2.850, P = 0.005) in combination treatment group were significantly lower than sorafenib monotherapy group. Compared with the control group, the body weight of nude mice in the treatment group decreased to a certain extent, but there was no statistically significant difference between epalrestat monotherapy group and control group (t = -1.599, P = 0.262), and combined therapy and sorafenib monotherapy group (t = -0.051, P = 0.96). Conclusion AKR1B10 inhibitor enhanced the inhibitory effect of sorafenib on hepatocellular carcinoma xenograft.

Aging and age-related ailments have emerged as critical challenges and great burdens within the global contemporary society.Addressing these concerns is an imperative task,with the aims of postponing the aging process and finding effective treatments for age-related degenerative diseases.Recent investigations have highlighted the significant roles of nicotinamide adenine dinucleotide(NAD+)in the realm of anti-aging.It has been empirically evidenced that supplementation with nicotinamide mononucleotide(NMN)can elevate NAD+levels in the body,thereby ameliorating certain age-related degenerative diseases.The principal anti-aging mechanisms of NMN essentially lie in its impact on cellular energy metabolism,inhibition of cell apoptosis,modulation of immune function,and preservation of genomic stability,which collectively contribute to the deferral of the aging process.This paper critically reviews and evaluates existing research on the anti-aging mechanisms of NMN,elucidates the inherent limitations of current research,and proposes novel avenues for anti-aging investigations.