Objective To explore the relationship between activation-induced cytidine deaminase (AID) expression and melanoma invasion, metastasis and prognosis, and to evaluate the clinical significance of AID. Methods An immunohistochemical study was conducted to detect the expression of AID in paraffin-embedded tissue sections from 80 cases of melanoma and 23 cases of pigmented nevus. The relationship between the expression of AID and clinicopathological and biological features of melanoma was analyzed. Results The expression rate of AID was significantly higher in melanoma than in pigmented nevus tissue specimens(53.75%(43/80)vs. 13.04%(3/23), P<0.05). AID expression was closely correlated with lymphatic metastasis, Clark grade, depth of invasion and prognosis of melanoma (all P<0.05), but was of no significant difference among patients of different age, gender or nationalities(all P > 0.05). Of 19 melanoma specimens with BRAF mutations, 17 expressed AID, including all the 15 melanoma specimens with the BRAFV600E mutation. Conclusions AID may induce BRAF mutations in melanoma, participate in melanoma invasion and metastasis, and be correlated with melanoma prognosis.

Objective To investigate the expression of granulocyte macrophage-colony stimulating factor(GM-CSF)in skin lesions and sera of patients with pustular psoriasis and psoriasis vulgaris.Methods Tissue specimens were obtained from the lesions of 15 patients with pustular psoriasis,15 patients with psoriasis vulgaris and 15 normal human controls.Immunohistochemistry and dual antibody sandwich enzyme-linked immunosorbent assay(ELISA)were carried out to detect the levels of GM-CSF in the tissue and serum specimens from the patients and normal human controls,respectively.Results Significantly higher levels of GM-CSF were observed in the tissue and serum specimens from patients with pustular psoriasis and psoriasis vulgaris compared with the normal controls(all P ＜ 0.01),as well as in those from the patients with pustular psoriasis compared with the patients with psoriasis vulgaris(both P ＜ 0.01).Conclusion GM-CSF may be involved in the pathogenesis of psoriasis.

Objective To investigate the clinical role of central venous pressure(CVP) to evaluate fluid responsiveness in septic shock patients. Methods 66 septic shock patients were studied, every patient was administered a volume challenge, before and after it, CVP, intrathoracic blood volume index (ITBVI),global end-diastolic volume index(GEDVI), cardiac index(CI), stroke volume index(SVI) were measured by PiCCO method. All the obtained values were analyzed by statistics method. Results Initial CVP in responders is significantly different from that in nonresponders; △ITBVI, △GEDVI, △CI, △SVI, △HR (△:changes) before and after volume challenge in responders were significantly different from those in nonresponders; the significance of △ITBVI, AGEDVI to predict volume responsiveness was strong indicated by high values of areas under the receiver operating characteristic curves (0.674 and 0.700, respectively).If patients were regrouped by CVP≤11 mm Hg(1 mm Hg=0.133 kPa) and CVP > 11 mm Hg, initial ITBVI and GEDVI in responders were not significantly different from that in nonresponders; △ITBVI,△GEDVI, △CI, △SVI before and after volume challenge in responders were significantly different from those in nom'esponders. Conclusion In septic shock patients, CVP play a guidance role to predict and evaluate volume responsiveness and when CVP was > 11 nun Hg, a positive response will be less likely. Initial volumetric parameters(intrathoracic blood volume and global end-diastolic volume) play a questionable role in predicting and evaluating volume responsiveness, changes before and after volume challenge maybe helpful.

Objective To investigate the influence of electrocardiogram(ECG)-controlled dose modulation on exposure dosage and image quality of cardiac CT imaging in a cardiac phantom with simulated fluctuant heart rate.Methods The basal heart rate of the cardiac pulsating phantom was set as 60 bpm.the experimental situations were divided as 6 groups according to different heart rates.The cardiac imaging was performed on the cardiac phantom when the ECG-controlled dose modulation was firstly turned off.The exposure dosage of each scan sequence was documented.The standard deviation of the CT values of the phantom was measured on the central slice after coronal reformation of the raw data.The quality of 2D and 3D images were scored.Thell cardiac imaging was performed when ECG modulation was on and set as four groups according to different modulation parameters.All the data were documented as before.The results from the five groups with and without ECG modulation current were analyzed bv F test and comparative rank sum test using the statistical software SPSS 10.0.Results Statistical analysis showed no significant difference(P＞0.05)between the SNR of images(SD value was 27.78 and 26.30)from the groups that full mA output at wide reconstruction phase(69%～99%)when the heart rate was fluctuant(≥7.5 bpm).There was also no significant difference(P＞0.05)between the quality of the 2D and 3D images.But there was a significant difference(P＜0.01)between the SNR of images(SD value was 26.78 and 29.90)that full mA was only used at 85%reconstruction phase when the heart rate Was fluctuant(≥7.5 bpm).The exposure dosage was remarkably reduced when the ECG modulated current was on than when it Was off under fluctuant heart rate.Furthermore.there were significant difierence(P＜0.01)among the difierent ECG modulated current parameter groups.The exposure dosage can be reduced by 44.7%under the situation that the heart rate was fluctuant.Whell the fluctuation of the heart rate was≤12.5 bpm,there wag no obvious relationship between the fluctuation of the heart rate and the exposure dosage (the variation was from 0.1 to 1.1 mSv),but if the heart rate fluctuation was＞12.5 bpm,the exposure dosage would increase obviously (from 0.6 to 1.7 mSv).Conclusion For cardiac imaging with 16-slice row CT,the application of ECG modulated current can effectively reduce the exposure dosage without compromising the image quality even if heart rate was fluctuant.

Objectlve To research and analyze the hemod)rnamic status of refractory septic shock associated cardiac dysfunction.Methods 70 refractory septic shock patients were studied.In the duration of pulmonary artery catheter(PAC)-directed hemodynamic optimization,the patients were divided into a cardiac dysfunction group and a control group.Hemodynamic parameters,arterial blood lactate concentration and APACHE II scores were obtained instantly after the placement of a PAC,then lactate clearance in 24 hours was surveyed and calculated.Subsequently the two groups of patients were regrouped by nonsurvivor and survivors respectively.All the obtained values were analyzed with statistic methods.Results 37% of the refractory septic shock patients was complicated with cardiac dysfunction.The age of the patients complicated with cardiac dysfunction was significantly higher than that of the patients of the control group.Central venous pressure(CVP),pulmonary artery obstruction pressure(PAOP),pulmonary artery pressure (PAP),systemic vascular resistance index(SVRI),pulmonary vascular resistance index(PVRI)and oxygen extraction ratio(O2ext)in the cardiac dysfunction group were significantly different from those in the control group.Cardiac output(CO),cardiac index(CI),oxygen delivery index(DO2I)and mixed venous oxygensaturation(S-v O2)were significantly lower than those of the patients in the control group.S -v O2 had a strong correlation witIl CI.If the patients were regrouped by nonsurvivors and survivors.in the patients complicated with cardiac dysfunction APACHE II scores were significantly higher in the nonsurvivors than survivors:the lactate clearance in 24 hours(median-25%)of the nonsurvivors was significantly lower than that of nonresponders(median 22%),P＜0.05.Conclusion (1)In refractory septic shock patients,cardiac dysfunction maybe the main reason leading to bad outcome.(2)Higher CVP and PAOP and lower S -v O2 indicate the onset of cardiac dysfunction.(3)The patients with significantly high initial arterial blood lactate level and the low lactate clearance in 24 hours had bad outcome.

Objective To explore whether emotion regulation mediates the relationship between occupational stress and job burnout in a large sample of nurses, in order to provide a targeted intervention. Methods Chinese Nurses Stressor Scale, Maslach Burnout Inventory-Human Services Survey, Emotion Regulation Questionnaire and Ruminative Responses Scale were used to investigate 602 nurses working in three tertiary hospitals in Jinan. SPSS 16.0 and AMOS 17.0 software were used to analyze the data. Results Job burnout were positively correlated with stressors, expression suppression and rumination (r=0.112–0.576, P<0.01), and negatively correlated with cognitive reappraisal (r=-0.277, P<0.01). Stressors were positively correlated with expression suppression and rumination (r = 0.140–0.403, P <0.01), and negatively correlated with cognitive reappraisal (r =-0.110, P < 0.01). Occupational stress could make a positive role on job burnout directly. Moreover, in the indirect approach, occupational stress could make a positive role on job burnout through the mediating role of cognitive reappraisal and ruminative, but not expression suppression. Conclusions Cognitive reappraisal and ruminative partially mediated the relationship between occupational stress and job burnout.

Objective To research the expression,methylated regulation and clinical significances of miR-34b in chidren with acute leukemia(AL).Methods The methylation status of miR-34b promoter CpG islands were detected with methylation-specific polymerase chain reaction (MSP) in patients with AL.Then the expression of miR-34b was compared,which was detected by Taqman real-time fluorescence quantitative polymerase chain reaction (qRT-PCR),between the AL patients and normal group,in order to analyze their relationship with the clinical indicators.Resuits In 8 leukemia cell lines (U937,HL-60,MV4-11,M2R,K562,Raji,CCRF,DAMI) showed methylation,the positive rate of the methyl was 100％.Thirty-one acute lymphocytic leukemia(ALL) pediatric patients were newly diagnosed,and 24 cases showed methylation,the methylation positive rate 77.42％ (24/31).Nineteen acute myeloid leukemia(AML) patients were newly diagnosed,and 8 cases showed methylation,the methylation positive rate was 42.11％ (8/19 cases).There was no methylation in the 23 cases of normal children.The relative expression levels of miR-34b in the normal group,the group of leukemia cell lines,the group of ALL pediatric patients with newly diagnosed,the AML group and the group with mixed lineage leukemia gene rearrangement MLL+ were 5.22 ± 1.15,0.03 ± 0.03,1.65 ± 0.69,0.18 ± 0.06,0.64 ± 0.34,respectively.The findings indicated that there were significant differences in the relative expression levels of miR-34b between the normal group and the group of leukemia cell lines,the ALL group,the AML group,and the MLL+ group.The relative expression and methylated level of miR-34b had no statistically difference in gender,age at diagnosis,WBC count,chromosome,fusion gene,MLL gene rearrangement,and the minimal residual disease(LDH) levels in newly diagnosed AML patients(all P ＞ 0.05).And the relative expression and methylated level of miR-34b had no statistically difference in gender,age at diagnosis,WBC count,immunophenotype,chromosome,fusion gene,MLL gene rearrangement,TEL/AML1 gene,risk stratification,the minimal residual disease (MRD) in thirty-three days and the LDH levels in newly diagnosed ALL patients(all P ＞ 0.05).But as for the response to prednisone experiment,there was a significant difference between the sensitive group and the non sensitive group(P ＜ 0.05).Conclusions The expression level of miR-34b in AL was significantly lower and it was regulated by methylation mechanism,which implies that miR-34b may play a role of a tumor suppressor gene in the pathogenesis of leukemia.MiR-34b may affect the early treatment response of ALL patients,and it may be an indicator of risk stratification and poor prognosis in pediatric ALL.

The transition metal cobalt, an essential cofactor for many enzymes in prokaryotes, is taken up by several specific transport systems. The CbiMNQO protein complex belongs to type-1 energy-coupling factor (ECF) transporters and is a widespread group of microbial cobalt transporters. CbiO is the ATPase subunit (A-component) of the cobalt transporting system in the gram-negative thermophilic bacterium Thermoanaerobacter tengcongensis. Here we report the crystal structure of a nucleotide-free CbiO at a resolution of 2.3 Å. CbiO contains an N-terminal canonical nucleotide-binding domain (NBD) and C-terminal helical domain. Structural and biochemical data show that CbiO forms a homodimer mediated by the NBD and the C-terminal domain. Interactions mainly via conserved hydrophobic amino acids between the two C-terminal domains result in formation of a four-helix bundle. Structural comparison with other ECF transporters suggests that non-conserved residues outside the T-component binding groove in the A component likely act as a specificity determinant for T components. Together, our data provide information on understanding of the structural organization and interaction of the CbiMNQO system.
Adenosine Triphosphatases ; chemistry ; Amino Acids ; chemistry ; Biological Transport ; Catalytic Domain ; Cobalt ; chemistry ; Crystallography, X-Ray ; Protein Binding ; Protein Conformation ; Protein Structure, Secondary ; Structure-Activity Relationship ; Thermoanaerobacter ; enzymology

The purpose of this study is to explore the effects of the HA sequence variation on the pathogenicity and antigenicity of avian influenza virus(AIV). Haemagglutinin (HA) genes from, 6 of 25 avian influenza viruses (AIVs) H9N2 strains with different pathogenicity isolated in central China during last 10 years were amplified by reverse transcriptase PCR (RT-PCR), completely sequenced and phylogenetically analyzed. The purpose of this study was to explore the effects of the HA sequence variation on the pathogenicity and antigenicity of AIV. The results showed that all 6 representative H9N2 isolates belong to low pathogenic AIVs, since none of the amino acid sequences at the cleavage site of the HA of the isolates possessed the basic motif required for highly pathogenic viruses (R-X-R/K-R). There were eight potential glycosylation sites in HA of the isolates, except that 3# and 12# had an extra one. The higher pathogenicity of 3# and 12# was probably due to the extra glycosylation site (145aa-147aa) in HA1, which might alter the conformational structure of HA resulting in the mutation or deletion of the binding sites of anti-HA antibody, and has effects on receptor binding sites thus changed the antigenicity of the virus. Our results suggested that attention should be paid to the transmission and natural evolution of H9N2 AIV in order to control AIV H9N2.
Animals ; Chickens ; China ; Computational Biology ; Glycosylation ; Hemagglutinin Glycoproteins, Influenza Virus ; chemistry ; genetics ; immunology ; metabolism ; Influenza A Virus, H9N2 Subtype ; classification ; genetics ; immunology ; isolation & purification ; Phylogeny ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Alignment ; Sequence Analysis, DNA

OBJECTIVETo study relationship between daunorubicin (DNR) pharmacokinetics and efficacy and toxicity in children with acute leukemia.

METHODS(1) The concentration of DNR in plasma of children with acute leukemia was determined by high performance liquid chromatography (HPLC)-fluorescence detection method. Plasma was sampled frequently from the start of the infusion till the end of 24 h. DNR pharmacokinetics was studied by determination of the concentrations. (2) Efficacy and toxicity were monitored in each period after chemotherapy. Laboratory studies included examination of bone marrow, white blood cell count, electrocardiogram, echocardiogram, myocardial enzymogram, the liver and kidney function.

RESULTS(1) DNR was eliminated from plasma in a two-compartment manner. The maximum concentration was seen 1 - 3 h after infusion. Cmax was 63.50 microg/L. Tmax was 1.45 h. The concentration decreased quickly to a low level of about 11.52 microg/L from the end of 2 hours infusion. There was a large inter-individual difference in pharmacokinetic parameters of DNR. The difference of CL was 9-fold, AUC was 8-fold, Cmax was 5-fold. (2) CL of male patients [57.99 L/(h.m(2))] was significantly lower than that of female patients [93.71 L/(h.m(2))] (P < 0.05). Tmax of children older than 6 years was 1.1 h, and that of children younger than 6 years was 1.8 h (P < 0.05); Cmax of children older than 6 years was 90.77 microg/L, younger than 6 years was 57.44 microg/L (P < 0.05).

CONCLUSION(1) There is a large inter-individual difference in pharmacokinetic parameters of DNR in children. It may predict individual variety of efficacy and toxicity. Therapeutic drug monitoring is important. (2) Male patients and children older than 6 years had a higher bioavailability and lower metabolism, toxicity may easily occur in such children, therefore they may need lower dose.

Antibiotics, Antineoplastic ; adverse effects ; pharmacokinetics ; therapeutic use ; Child ; Child, Preschool ; Chromatography, High Pressure Liquid ; Daunorubicin ; adverse effects ; pharmacokinetics ; therapeutic use ; Drug Monitoring ; Female ; Humans ; Infant ; Leukemia ; drug therapy ; metabolism ; Male