Adolescent ; Child ; Child, Preschool ; Core Binding Factor Alpha 3 Subunit ; genetics ; metabolism ; DNA Methylation ; Female ; Humans ; Infant ; Lymphoma ; genetics ; metabolism ; Male ; Promoter Regions, Genetic

Objective To explore the effects of peripheral stem cell transplantation on extremely severe bone marrow form of acute radiation sickness.Methods One patient was radiated aecidently with the radiation dosage of 9～15 Gy and diagnosed as extremely severe bone marrow form of acute radiation sickness.Pretreatment was performed at 4th day after the accident and 3 days later,HLA- matched allogeneic stem cell transplantation on the patient was performed.Graft versus host disease (GVHD) was prevented with cyclosporin A (CsA) and mycophenolate mofetil (MMF).Results The haematopoiesis was recovered at 9th day after transplantation.At 11th day after transplantation, WBCs were increased to 14.74?10~9/L and returned to the normal levels subsequently,number of platelets risen to 51?10~9/L and hemaglobin was over 80 g/L.TRS-PCR and blood type dynamic detection testified that the donor's cells were stably implanted,the chromosome aberration and micro- nuclei disappeared after transplantation,and the patient's blood type changed into the donor's at 27th day after transplantation.But the radiation injury were still getting worse complicated with multiple infections,At 68th day after transplantation (75 days after the accident),the patient was died of mul- tiple organs failure.Conclusion Extremely severe bone marrow form of ARS can achieve hematopoie- sis recovery by allogeneic stem cell transplantation,but only hematopoiesis recovery can not cure the immunodefficiency and the radiation injury of the whole body.

Objective To investigate the characteristics of the cognitive impairment about attentional network among amphetamine-induced psychiatric disorders. Methods Amphetamine-induced psychiatric disorders ( n = 100) and normal controls ( n = 100) were assessed with Attentional Network Test(ANT) in the first week and the fourth week. Results Compared with the control group, the first ANT's response time was significantly increased, and the correct rate, orienting and executive control network were significantly reduced in Amphetamineinduced psychiatric disorders( eg:response time ( 867. 37 ± 272.24 ) ms vs ( 668.56 ± 136. 20 ) ms, correct rate (0.88 ±0.06 ) ms vs (0.88 ±0.06) ms ,orienting( - 217.86 ± 198.00 ) ms vs ( -59.67 ± 85.07 ) ms and executive control network ( 184.74 ± 66.61 ) ms vs ( 74.71 ± 50.77 ) ms, P ＜ 0.01 ), but the alerting network was higher ( ( 151.17 ± 198.27 ) ms vs (50.60 ± 67.47 ) ms). In the second ANT results, there was no significant difference between two groups. Compared with the first ANT results of amphetamine-induced psychiatric disorders, the second ANT had shorten response time ,that the correct rate, orienting and executive control network were significantly increased(P ＜ 0.01 ). Conclusion These results suggest that amphetamine-induced psychiatric disorders have impairment in cognitive function, but these impairment can be recovered within one month.

OBJECTIVETo investigate the methylation status of zonula occludens-1 (ZO-1) gene promoter and its clinical significance in children with stage IV non-Hodgkin lymphoma (NHL) and to provide a basis for further etiological study and early diagnosis of this disease.

METHODSFifty-five children with a confirmed diagnosis of stage IV NHL (40 cases of T-NHL and 15 cases of B-NHL) were selected as the case group, and 20 children with diseases other than hematologic malignancies were selected as the control group. Bone marrow samples were collected from these subjects. Methylation-specific PCR (MS-PCR) was applied to evaluate the methylation status of ZO-1 gene promoter, and the integrated optical density (IOD) was determined. RT-PCR was used to measure the mRNA expression of ZO-1.

RESULTSMS-PCR showed that the methylated bands of ZO-1 gene promoter were found in 39 (70.9%) of 55 patients in the case group before treatment, while no ZO-1 gene promoter methylation was detected in the control group. With close tracking of 47 cases in the study group, consisting of 32 cases of T-NHL and 15 cases of B-NHL, the rates of ZO-1 gene promoter methylation prior to treatment were 72% and 67%, respectively, (P>0.572). The cases of T-NHL and B-NHL showed no significant changes in methylation rate in the early and middle phases of chemotherapy (P>0.05), but they showed significant changes in methylation rate in the late phase of chemotherapy (P<0.05). RT-PCR showed that the NHL cases carrying methylated ZO-1 gene had no mRNA expression of ZO-1, while all children in the control group had mRNA expression of ZO-1. There was no linear relationship between the total number of peripheral blood leukocytes and ZO-1 gene IOD (r=0.093, P=0.575); a positive correlation was found between the number of malignant cells in bone marrow and ZO-1 gene IOD (r=0.669, P<0.001).

CONCLUSIONSZO-1 gene shows a hypermethylation status in children with NHL, and the methylation level is positively correlated with the number of malignant cells in bone marrow. ZO-1 may be used as a novel molecular marker in early diagnosis, outcome assessment, prognostic evaluation, and detection of minimal residual disease.

Adolescent ; Child ; Child, Preschool ; DNA Methylation ; Female ; Humans ; Infant ; Lymphoma, Non-Hodgkin ; genetics ; Male ; Promoter Regions, Genetic ; Zonula Occludens-1 Protein ; genetics

Effects of lysophosphatidic acid (LPA), an extracellular phospholipid signal, on the proliferation of rat embryonic neural stem cells (NSCs) and their differentiation into microtubule-associated protein 2 (MAP2)-positive and choline acetyltransferase (ChAT)-positive, i.e. cholinergic-committed neurons, were observed in vitro by [(3)H]-thymidine incorporation, immunocytochemistry, Western blot and other techniques. The results showed that: (1) Lower concentrations of LPA (0.01~1.0 mumol/L) dose-dependently enhanced the uptake of [(3)H]-thymidine by NSCs cultured in specific serum-free medium, indicating a significant promotive action of LPA on the proliferation of NSCs. (2) After fetal bovine serum which induces and commences the differentiation of NSCs, was used in the medium, the lower concentrations of LPA increased the percentages of both MAP2- and ChAT-immunoreactive neurons, with a peak at 0.1 mumol/L LPA in two cases. (3) The promotive effects of LPA on the differentiation of MAP2- and ChAT-positive neurons were also supported by the up-regulation of the expressions of both MAP2 and ChAT proteins detected by Western blot. (4) At the early phase of differentiation of NSCs, the cell migration and neurite extension were enhanced significantly by lower dosages of LPA under phase-contrast microscope. These results suggest that LPA within certain lower range of concentrations promotes the proliferation of NSCs and their differentiation into unspecific MAP2-positive and specific cholinergic-committed neurons, and also strengthens the migration and neurite extension of the newly-generated neuronal (and also glial as reported elsewhere) progenitors.
Animals ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Cholinergic Neurons ; cytology ; Embryonic Stem Cells ; drug effects ; Lysophospholipids ; pharmacology ; Neural Stem Cells ; drug effects ; Rats

To study the effect of lysophosphatidic acid (LPA) on the differentiation of embryonic neural stem cells (NSCs) into neuroglial cells in rats in vitro, both oligodendrocytes and astrocytes were detected by their marker proteins galactocerebroside (Gal-C) and glial fibrillary acidic protein (GFAP), respectively, using double-labeling immunocytochemistry. RT-PCR assay was also used for analyzing the expression of LPA receptors in NSCs. Our results showed that: (1) LPA at different concentrations (0.01-3.0 mumol/L) was added to culture medium and cell counting was carried out on the 7th day in all groups. Exposure to LPA led to a dose-dependent increase of oligodendrocytes with the response peaked at 1.0 mumol/L, with an increased percentage of 32.6% (P<0.01) of total cells as compared to that of 8.5% in the vehicle group. (2) LPA showed no effect on the differentiation of NSCs into astrocytes. (3) RT-PCR assay showed that LPA(1) and LPA(3) receptors were strongly expressed while LPA(2) receptor expressed weakly in NSCs. These results suggest that LPA at low concentration might act as an extracellular signal through the receptors in NSCs, mainly LPA(1) and LPA(3) receptors, to promote the differentiation of NSCs into oligodendrocytes, while it exhibits little, if any, conceivable effect on the differentiation of NSCs into astrocytes.
Animals ; Cell Differentiation ; drug effects ; Cells, Cultured ; Lysophospholipids ; pharmacology ; Neural Stem Cells ; cytology ; drug effects ; Neuroglia ; cytology ; Rats ; Receptors, Lysophosphatidic Acid ; metabolism

Objective To approach potential abnormalities of neuro-chemical compounds in cerebrum of obsessive-compulsive disorder and to analyze the relationship among the abnormalities with duration of illness and symptom severity. Methods 19 patients with obsessive-compulsive disorder and 22 comparison subjects were scanned by 1H magnetic resonance spectroscopy to exam bilateral prefrontal lobe, temporal lobe, parietal lobe, occipital lobe, anterior cingutate and caudate nucleus, hippocampus as well as splenium and genu of corpus callosum,thalamus. The ratios of N-acetylaspartate (NAA) and choline (Cho) to creatine (Cr) were respectively recorded.The severities of obsessive-compulsive symptoms were assessed by Yale-Brown Obsessive-Compulsive Scale. Results ( 1 ) The ratios of NAA/Cr in right caudate nucleus and left hippocampus were higher than those in normal controls (1.23 ±0.37 vs 1.0 ±0.33, t=2.14, P=0.039;1.34 ±0.25 vs 1. 10 ±0.45, t=2.41, P=0.021 ), but NAA/Cr ratios in genu of corpus callosum were lower(0. 97 ±0.30 vs 1.19 ± 0. 26, t = -2.47, P= 0.018 ).(2) The Cho/Cr ratios in right caudate nucleus and left temporal lobe were higher than those in control groups (1.09±0.51 vs0. 67±0.21,t=3.32, P=0.003;2.58±0.62vs0.84±0.17, t=2.21,P=0.03). (3) The duration of illness was negatively correlated with the Cho/Cr ratios of right prefrontal lobe ( r = - 0. 507, P =0. 027 ). (4) The NAA/Cr ratios of genu of corpus callosum as well as the Cho/Cr ratios of left temporal lobe were negatively correlated with YBOCS score ( r 1 = - 0.457, P = 0.049; r 2 = - 0. 585, P = 0.009 ). Conclusion Neuronal functions increase in right caudate nucleus and left hippocampus which are opposite in genu of corpus callosum. These abnormalities may play an important role in pathogenesis of OCD.

Objective To explore the impulsivity and aggressivity,and its treatment outcomes of the inpatients with intemet addiction disorder (IAD) by intergration interview. Methods Barratt Impulsiveness Scale ( BIS), Buss Aggressive Scale (BAS) were used to assess the impulsiveness and aggressivity in 58 IAD patients, at the first week and after the point of intergration interview 3 months,54 normal subjects in the control group were conducted by BIS and BAS only when they were recruited. Results ①The intemet addiction group had significantly higher scores on the BIS and BAS total scores than the control group at the first week ( BIS score 99.3 ±15. 1vs 75.0 ± 15.4, t=8.47, P＜0. 01; BAS score 78.3 ±24.4 vs 54.8 ± 17.7, t=5.87 , P＜0. 01 ). IAD group had lower scores on the total scores of BIS-Ⅱ and BAS after intergration interview than before, but the subscales and total scores were higher than those in the control group ( BIS score 86.3 ± 16.6 vs 75.0 ± 15.4, t =4.98, P ＜ 0.01 ;BAS score 66.2 ± 22.6 vs 54.8 ± 17.7, t = 3.65, P ＜ 0. 01 ). ②Total score of SCL-90 in IAD group were significantly correlated with the BAS total score ( r=0. 376, P＜0. 01 ) ,and the decreased SCL-90 total score was also related with the decreased BAS score ( r= 0.508, P＜ 0. 01 ). Conclusion This study suggests that IAD group exhibit more impulsivity and aggressivity than those in the control group. After interview, their impulsivity and aggressivity are significantly decreased, but are still higher than those in the normal control group.

Objective To investigate the expression of nucleotide-binding oligomerization domain protein 2 (NOD2)in serum of patients with hepatocellular carcinoma (HCC),and to analyse the roles of NOD2 in HCC development and its clinical diagnostic value.Methods This study including 66 patients with HCC in the hospi-tal from March 1,2013 to December 31,2014 and 61 healthy controls.Serum NOD2 levels were determined by enzyme-linked immunosorbent assay (ELISA).Analysis of significance was performed with rank sum test using SPSS statistical 16.0 software.Results Serum levels of NOD2 in HCC patients were 171 pg/ml,significantly higher than that of healthy controls(95 pg/ml,Z =-5.00,P =0.00),and the serum NOD2 levels were correla-ted with clinical stage of HCC (H=56.26,P =0.00).Compared with the serum NOD2 levels in stageⅠ,Ⅱpatients (106 pg/ml)and healthy controls (95 pg/ml),the serum NOD2 level in stage Ⅲ and Ⅳ (220 pg/ml) were significantly increased (χ2 =31.24,P =0.00;χ2 =47.23,P =0.00),but the expression of NOD2 in stageⅠandⅡwere nearly equal to that of the healthy controls (χ2 =0.36,P =0.83).The ROC analysis revealed that the best diagnostic cutoff-point of serum NOD2 levels for predicting the Ⅲ and Ⅳ stages of HCC was 148.78 pg/ml,meanwhile corresponding sensitivity was 89.1% and specificity was 77.0%.Additionally,corre-lation analysis demonstrated that there was no significant correlation between NOD2 and alpha-fetal protein (r =0.44,P =0.14).Survival curves obtained that the survival time of HCC patients with NOD2 serum concentrations≥ 200 pg/ml was significantly less than that <200 pg/ml (χ2 =15.32,P <0.05).Conclusion NOD2 is highly expressed in the serum of HCC patients,especially in advanced patients,which is possibly involved in the development of HCC and has the potential to become an effective marker used for HCC diagnosis.

Batifiban, a synthetic cyclic peptide, is a potent platelet glycoprotein GPIIb/IIIa antagonist which may be useful in the treatment and prevention of acute coronary syndromes. The pharmacokinetics and pharmacodymanic (inhibition of platelet aggregation) effects, and tolerability of batifiban were investigated in healthy subjects following single bolus injection with doses of 55, 110, or 220 microg/kg, or multiple doses of an bolus followed intravenous infusion for 24 h (180 microg/kg plus 2.0 microg/min.kg, and 220 microg/kg plus 2.5 microg/min.kg) in this phase I clinical trial. Plasma levels of batifiban and areas under the curve were found to be proportional to doses. Batifiban was rapidly eliminated with a half-life of approximately 2.5 h. Significant differences were noted for plasma levels of batifiban and areas under the curve between males and females. No significant differences in the terminal half-life were found between males and females. Batifiban reversibly inhibited ex vivo platelet aggregation in a dose- and concentration-dependent manner, consistent with its mechanism as a GPIIb/IIIa antagonist. Single and multiple intravenous doses of batifiban were found to be safe and well tolerated in healthy subjects. These results support a bolus injection plus intravenous infusion regimen of batifiban for the treatment and prevention of acute coronary syndromes.
Injections, Intravenous ; Peptides, Cyclic/*pharmacokinetics ; Peptides, Cyclic/*pharmacology ; Platelet Aggregation Inhibitors/adverse effects ; Platelet Aggregation Inhibitors/*pharmacokinetics ; Platelet Aggregation Inhibitors/*pharmacology ; Platelet Glycoprotein GPIIb-IIIa Complex/*antagonists & inhibitors ; Young Adult