Purpose:To explore the effects of stem cell factor(SCF) in combination with erythropoietin (EPO) on erythropoiesis in patients with anemia associated with non-Hodgkin's lymphoma (NHL). Methods:Bone marrow (BM) mononuclear cells (MNC) from NHL patients and normal simples were cultured for 7 consecutives days in the presence or absence of SCF, EPO, and SCF+EPO in liquid medium. Erythropoiesis was analyzed by calculating the fraction of recovered erythroid cells and by flow cytometry. Results:Cultures stimulated with SCF+EPO contained a marked increased fractions of recovered erythroid cells compared to cells cultured in EPO alone in NHL simples (P

Aim To study the role of TNF-α/NF-κB signaling in matrix metalloproteinase ( MMP)-9 expres-sion induced by lipopolysaccharide ( LPS ) in airway epithelial cells, and to investigate the effects of lenti-virus mediated RNAi targeting a disintegrin and metal-loproteinase 17 ( ADAM17 ) gene on MMP-9 expression induced by LPS. Methods The ADAM17 siRNA ex-pression vector was constructed, and packaged to re-combinant lentivirus in 293T cells. The HBE4-E6/E7 cells were pretreated for 30 min by NF-κB inhibitor ( PDTC) and a recombinant human TNFR p75-Fc fu-sion protein ( Etanercept) , or infected by the recombi-nant lentivirus for 72 h, and then stimulated for 24 h by LPS or TNF-α. The release of TNF-α was detected by ELISA. The mRNA and protein levels of MMP-9 were analyzed respectively by RT-PCR and Western blot. NF-κB activity was detected by electrophoretic mobility shift assay. Results LPS and TNF-α signifi-cantly increased MMP-9 mRNA and protein expressions and the activation of NF-κB in HBE4-E6/E7 cells ( P<0. 05 ) . Etanercept and PDTC significantly inhibited MMP-9 expression and the activation of NF-κB induced by LPS ( P<0. 05 ) . Lentivirus mediated RNAi targe-ting ADAM17 significantly decreased TNF-α produc-tion, inhibited MMP-9 mRNA and protein expressions and the activation of NF-κB induced by LPS in HBE4-E6/E7 cells ( P <0. 05 ) . Lentivirus mediated RNAi targeting ADAM17 did not inhibit MMP-9 mRNA and protein expressions and the activation of NF-κB in-duced by TNF-α ( P>0. 05 ) . And PDTC significantly inhibited MMP-9 mRNA and protein expressions and the activation of NF-κB induced by TNF-α ( P <0. 05 ) . Conclusions TNF-α/NF-κB signaling partic-ipates in the regulation of MMP-9 expression induced by LPS in airway epithelial cells, and lentivirus-media-ted RNAi targeting ADAM17 plays an important role in that signaling pathway upstream by regulating TNF-αrelease.

Objective To explore the expression and significance of p53 and p21_(WAF1)proteins in hep- atocellular carcinoma(HCC).Methods Immunohistochemical(S-P)method was used to detect the expression of p53 and p21~(WAF1)proteins in the 41 patients with HCC and 30 cases of paracancerous tissues.Results The positive rates of p53 and p21~(WAF1)proteins were 43.9 % and 75.6 % respectively.The expression of the proteins was significantly higher in tumor than that in corresponding paracancerous tissue(P0.05). p53 ex- pression showed significant difference in different pathologic grades and cases with or without intrahepatic metastasis and thrombus in the portal veins(P

Objective To explore the differences in clinical and laboratory parameters between elderly and non-elderly patients with acute lymphoblastic leukemia (ALL).Poor prognostic factors in elderly patients were explored to guide the individualized treatment.Methods Two hundred and seventy-nine ALL patients were divided into two groups:elderly group with their age more than 60 years (60-79 years) and nonelderly group with their age less than 60 years (14-59 years).The differences in clinical and laboratory parameters,abnormal molecular genetics on related genes,including IKZF1,PAX5,NOTCH1,PHF6,SH2B3,LEF1,and JAK1,as well as the correlations with treatment response and clinical outcome were compared between the two groups.Results Males accounted for a smaller part in elderly group [42.9 ％ (21/49) vs.61.7 ％ (142/230),P =0.015].The percentage of B cell lineage ALL (B-ALL),Philadelphia chromosome positive (Ph+) and CD33 positive rate were higher in elderly group compared with those in non-elderly group [87.8 ％ (43/49) vs.70.4 ％ (162/230),P=0.009;47.8 ％ (22/49) vs.27.4 ％ (58/230),P=0.007;56.8 ％ (21/49) vs.39.0 ％ (64/230),P =0.049,respectively].While both lymphodenopathy and total complete remission (CR) rate gained the upper hand in non-elderly group [38.9 ％ (81/230) vs.20.0 ％ (9/49),P=0.016;91.3 ％ (178/195) vs.68.3 ％ (28/41),P＜ 0.001,respectively].Moreover,elderly group had lower 3-month,6-month,12-month and 24-month overall survival (OS) rates (64.6 ％ vs.84.4 ％,P=0.001;50.0 ％ vs.73.8 ％,P=0.001;29.2 ％ vs.52.4 ％,P=0.003;6.2 ％ vs.26.2 ％,P=0.003,respectively) than those of non-elderly group.No significant differences in mutation rates of PAX5,NOTCH1,PHF6,SH2B3,LEF1 and JAK1 were found (all P ＞ 0.05).Conclusions Compared with non-elderly ALL patients,elderly ones harbor their intrinsic characteristics which might give rise to inferior outcomes.As a consequence,more attention should be poured into treating this particular group of ALL patients to improve their prognosis.

Objective To study the effect of injured podocytes on glomerular maturation and its underlying mechanism in neonatal mice.Methods Single i.p.injection with puromycin aminonucleoside (PA,0.1 mg/g BW) was given to ICR neonatal mice at day 1 after birth (1 dpp). Littermates injected with normal saline (NS) were used as control.Animals were examined for urine protein,blood pressure,kidney weight/body weight (KW/BW),renal histology at 2,4,8,12, 30,60 and 90 dpp (n=6～9 for each group).Immunohistochemistry and quantitative RT-PCR were performed to examine the expression of WT-1,CD31,VEGF,Flk-1,Ang-1,Ang-2,Tie-1 and Tie-2.Results Mice with PA injection had lower kidney weight and body weight at all time points as well as lower KW/BW at 4,8,12 dpp when compared with NS controls.Electron microscopy revealed nearly complete foot process effacement and segmental microvillous transformation as early as 1 day after PA injection.PA-injected kidneys showed fewer capillary loops and decreased maturation index as well as less CD31-positive endothelium in cortical glomeruli at 12 dpp. Glomerular mesangial injury and developing glomerulosclerosis along with proteinuria were noted in PA-injected kidneys starting from 30 dpp.Significantly increased systolic blood pressure was detected at 60 dpp in PA mice.Compared with NS injection,PA injection significantly induced decreased mRNA expression of Flk-1 and Tie-2 as well as increased expression of Ang-1,without obvious changes of VEGF at 2 dpp.Conclusions Podocytes in neonatal kidney of ICR mice are susceptible to PA. Such podocyte injury can alter the expression of VEGF and angiopoietin system in glomeruli,leading to abnormal development of glomerular capillaries,and subsequent proteinuria,hypertension and glomerulosclerosis.

Long noncoding RNAs (lncRNAs) have recently been discovered and are increasingly recognized as vital components of modern molecular biology.Accumulating evidence shows that lncRNAs have emerged as important mediators in diverse biological processes such as cell differentiation,pluripotency,and tumorigenesis,while the function of lncRNAs in the field of normal and malignant hematopoiesis remains to be further elucidated.Here,we widely reviewed recent advances and summarize the characteristics and basic mechanisms of lncRNAs and keep abreast of developments of lncRNAs within the field of normal and malignant hematopoiesis.Based on gene regulatory networks at different levels of lncRNAs participation,lncRNAs have been shown to regulate gene expression from epigenetics,transcription and post transcription.The expression of lncRNAs is highly cell-specific and critical for the development and activation of hematopoiesis.Moreover,we also summarized the role of lncRNAs involved in hematological malignancies in recent years.LncRNAs have been found to play an emerging role in normal and malignant hematopoiesis,which may provide novel ideas for the diagnosis and therapeutic targets of hematological diseases in the foreseeable future.

To investigate the effect of flavonoids from Sophora flavescens in aging mice induced by D-galactose and its mechanism. Totally 60 mice were randomly divided into six groups: the control group, the model group, the piracetam group (positive control group) and flavonoids from S. flavescens low, medium and high doses groups. Except for the control group, all of the rest groups were subcutaneously injected with D-galactose (160 mg x kg(-1)) for successively 30 days to establish the sub-acute senescent model. Meanwhile, flavonoids from S. flavescens low, medium and high doses groups were respectively administered with 150, 300 and 600 mg xkg-('1)of flavonoids from S. flavescens for 30 days. The learning and memory abilities of mice were determined by avoiding darkness ex-eriment and jumping stair experiment. The contents of malondialdehyde (MDA) tumor necrosis factor-aα NF-aα the activities of superoxide dismutase (SOD) monoamine oxidase-B (MAO-B) Na'(+)K'(+)-ATPase and Ca2(+ )-ATPase in the brain of mice were deter-ined respectively after the behavioral experiments. The activity of lactic dehydrogenase ( DH) in blood serum was also determined and analyzed by microscope after HE staining to observe the changes in hippocampal organizational structure. Compared with the model group, flavonoids from S. favescens medium and high doses groups showed significantly increases in the latency of avoiding darkness and jumping stair experiments; flavonoids from S. fllvescens low, medium and high doses groups and the piracetam group showed de-reases in the numbers of errors in avoiding darkness experiment; the flavonoids from S. flavescens high dose group and the piracetam group showed reduction- n the number of errors in jumping stair experiment (P <0 . 5 or P <0 . 1). Flavonoids from S. flavescens me-ium and high doses groups and the piracetam group showed improvements in the activities of SOD, Na'(+)K'(+)ATPase in the brain of mice and declines in the contents of MDA and TNF-aα the activity of MAO-B in the brain of mice, the activity of LDH in blood serum (P <0 . 5 or P <0 . 1). Flavonoids from S. flavescens low, medium and high doses groups and the piracetam group also showed im-rovement in the activity of Ca2(+ )ATPase, with statistical difference from the model group (P <0 . 5 or P <0 . 1). The pathological result showed decreases in the number of cells of hippocampal dentate gyrus area, sparse cell arrangement, incomplete cellular mor-hology, scarce cytoplasm, blurred boundary between nucleus and cytoplasm, nuclei anachromasis, irregular pyknosis and unconspicu-us nucleoli in the model group. Compared with the model group, flavonoids from S. flavescens low, medium and high doses groups and the piracetam group showed improvements in hippocampal organization tissues. Flavonoids from S. favescens can improve the learning and memory ability of senescent mice induced by D-galactose. Its mechanism may be correlated with the enhancement of anti-oxidative actions by lowering TNF-aαcontent, which results in the stability of cell membrane and the reduction in MAO-B activity.
Aging ; drug effects ; metabolism ; psychology ; Animals ; Brain ; drug effects ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Flavonoids ; administration & dosage ; Galactose ; adverse effects ; Hippocampus ; drug effects ; metabolism ; Humans ; Learning ; drug effects ; Male ; Malondialdehyde ; metabolism ; Mice ; Sophora ; chemistry ; Superoxide Dismutase ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

To optimize indices of molecular identification for authentication of Ginseng Radix et Rhizoma and Panacis Quinquefolii Radix, four indices, including sequence similarity, specific positions, genetic distance and phylogenetic tree, were compared based on trnL-trnF sequences. Total DNA was extracted from Ginseng Radix et Rhizoma and Panacis Quinquefolii Radix, and trL-trnF sequences were amplified and sequenced. Sequence similarity was calculated by BLAST analysis. Specific positions were compared by DNAman software. Genetic distance and phylogenetic tree were analyzed by Mega software. The results showed that the inter-specific and intra-specific similarity of P. ginseng and P. quinquefolius respectively was 100% and 99. 6%. There were four specific positions at G153A, T463A, C732G and T818C. The inter-specific genetic distance (0) of trL-trnF sequences was lower than intra-specific genetic distance (0. 004). P. ginseng can be distinguished from P. quinquefolius based on the phylogenetic tree. It is concluded that Ginseng Radix et Rhizoma and Panacis Quinquefolii Radix can be authenticated by identification indices of sequence similarity, specific positions, genetic distance and phylogenetic tree. Index of specific positions based on trnL-trnF sequences is the most efficient index to authenticate Ginseng Radix et Rhizoma and Panacis Quinquefolii Radix.
Chloroplasts ; genetics ; DNA Barcoding, Taxonomic ; methods ; Panax ; classification ; genetics ; Phylogeny ; Plant Proteins ; genetics ; Rhizome ; classification ; genetics

Aged ; Female ; Heart Atria ; pathology ; Humans ; Middle Aged

The aim of this study was to investigate the population pharmacokinetic characteristics of high-dose methotrexate (HDMTX) administered in children with acute lymphoblastic leukemia (ALL) for individualizing methotrexate dose regimen with routine plasma concentration data. The data of 329 children with acute lymphoblastic leukemia administering HDMTX in hospital were collected from 2003 to 2006. Population pharmacokinetics model, parameters, inter-and intra-individual variation were estimated by nonlinear mixed effect modes (NONMEM) software. The effects of the covariates including sex, age, body weight, alkalization and hydration volumes as well as biochemical parameters on the clearance and apparent volume of distribution of methotrexate were explored and the final model was established. The results showed that according to one compartment open pharmacokinetic model with first-order absorption and first-order elimination used in the modeling procedure, the factor that significantly influenced the clearance and apparent volume of distribution of methotrexate was weight (p<0.05). The final model in this study was: CL=7.0 x [1 + 0.0218 x (WT-31.1)] x EXP (eta(CL)) (L/h); V=32.8 x [1 + 0.0288 x (WT-31.1)] x EXP (eta(V)) (L), where 31.1 (kg) was the average body weight of the population. The inter individual variation (CV) of CL and V were 19.4% and 31.0% respectively. It is concluded that the population pharmacokinetic model of HDMTX in children with ALL is established. The obtained final model and population pharmacokinetics parameters of methotrexate may be useful for individualization treatment.
Antimetabolites, Antineoplastic ; adverse effects ; pharmacokinetics ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Dose-Response Relationship, Drug ; Female ; Humans ; Male ; Methotrexate ; administration & dosage ; pharmacokinetics ; Models, Biological ; Nonlinear Dynamics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; metabolism