Ojective To investigate the relationship between the serum adiponectin concentration and insulin resistance in patients with obesity and diabetic patients. Methods Fasting serum adiponectin concentration was measured by RIA in 19 normal subjects, 23 obese subjects, 31 diabetic patients without obesity and 26 diabetic patients with obesity. Results There was no significant difference in serum adiponectin concentration between nomal and obese subjects, and between type 2 diabetics without obesity and type 2 diabetics with obesity . The serum adiponectin concentrations was significantly higher in type 2 diabetics without or with obesity than that in nomal and obese subjects. There was significant difference in serum adiponectin concentration between female and male subjects. Body mass index (BMI), waist circumference(WC), waist-hip ratio (WHR), body fat percentage (BF%), fasting plasma glucose (FPG), insulin sensitivity index (ISI), triglyceride (TG) and high density lipoprotein-C (HDL-C) were significantly correlated with serum adiponectin concentration. A stepwise mulitiple linear regression analysis showed that HDL-C, FPG, WC, BF% entered the regression equation. Conclusion Serum adiponection level was associated with sex, obesity, type 2 diabetes mellitus and insulin resistance.

Objective To determine the minimal local analgesic dose (MLAD) of hypobaric levobupivacaine in elderly patients undergoing spinal anesthesia during lower limb surgery. Methods A total of 25 patients underwent spinal anesthesia with hypobaric levobupivacaine during lower limb surgery. The initial dose of levobupivaeaine was 7.50 mg for the first patient. The dose for next patient was added by 0.25 mg if the level of sensory block was lower than that of T10, conversely the dose was subtracted by 0.25 mg. The MLAD of hypobaric levobupivacaine was calculated with up-and-down sequential experiment according to Dixon-Messay method. Results The MLAD of hypobaric levobupivacaine were 6.67 mg (95% confidence interval: 6.34-7.25). The anesthesia effects of all patients were good. The degree of motor blockade of the healthy leg was less than another leg.The intraoperative and postoperative complications rates associated with spinal anesthesia were low.Conclusions The MLAD of hypobaric levobupivacaine is 6.67 mg in elderly patients undergoing spinal anesthesia during unilateral lower limb surgery.

Objective To explore the function of the baseline model for end-stage liver disease (MELD) scores,MELD-Na scores and iMELD scores in short-term prognosis in the initial treatment of hepatitis B virus (HBV) related acute-on-chronic liver failure (ACLF) patients.Methods 232 HBV-related ACLF patients who received initial treatment in 302 Military Hospital of China from January 2011 to January 2013 were enrolled in this prospective clinical follow-up.The relationship between the baseline MELD scores,MELD-Na scores,iMELD scores and clinical outcomes were analyzed,and the value of these three models for short term prognosis was assessed.Results Finally the 12-week clinical follow-up was completed in 191 patients,with the completion rate of 82.33％.Eighty-five patients died,with the fatality rate of 44.50％.Compared with the survival group,in non-survival group,the baseline of MELD scores (26.65 ± 7.75 vs.21.19 ± 5.42,t=-5.720,P=0.000),MELD-Na scores (29.16 ± 11.35 vs.21.72 ± 6.33,t=-5.729,P=0.000),iMELD scores (47.19 ± 10.96 vs.38.02 ±7.01,t=-7.011,P=0.000),total bilirubin [TBil (μmol/L):374.3 ± 150.1 vs.305.5 ± 147.1,t=-3.182,P=0.002],creatinine [Cr (μmol/L):110.7 ±90.1 vs.71.1 ± 35.1,t=-4.157,P=0.000] and international normalized ratio (INR:2.3 ± 0.9 vs.2.0 ± 0.6,t=-2.754,P=0.006) were significantly increased,but the baseline of serum Na+ (mmol/L:132.8 ± 6.1 vs.136.7 ± 5.1,t=4.861,P=0.000) was significantly lowered.It was shown by Spearman correlation analysis thai the baseline MELD scores,MELD-Na scores and iMELD scores all had positive correlation with the short-term prognosis of patients (r value was 0.398,0.404,and 0.470,respectively,all P=0.000),the baseline of serum Na+ had a negative correlation with the short-term prognosis of patients (r=-0.365,P=0.000).It was shown by receiver operating characteristic curve (ROC curve) that the cut-off scores of the baseline of MELD scores,MELD-Na scores and iMELD scores were 25.07,25.43 and 43.11 respectively,and the area under ROC curve (AUC) of the baseline of MELD scores,MELD-Na scores and iMELD scores were 0.731,0.735 and 0.773,respectively.The sensitivity of the three models was 55.3％,57.7％,63.5％,and the specificity was 84.9％,84.0％,84.9％ respectively.The value of the three models had no difference in short-term prognostic prediction.According to the respective cut-off score,the three prediction models were divided into four groups,and all of them had differences in fatality rate on the whole (x2 for MELD scores was 34.740,P=0.000; x2 for MELD-Na scores was 36.861,P=0.000; x2 for iMELD scores was 50.127,P=0.000).The mortality was elevated gradually as the equation scores increased.Conclusion The baseline of MELD scores,MELD-Na scores and iMELD scores can predict well the short-term prognosis of the initial treatment in HBV-related ACLF patients,and have relatively good clinical value for guiding therapy.

OBJECTIVE To evaluate the genotoxicity of naproxen (NPX) impurities acetylnerolin (Ace). METHODS The genotoxicity of Ace was predicted by ADMET, Derek and Sarah with the quanti?tative structure-activity relationship (QSAR). The chromosomal aberration and bacterial reverse-muta?tion (Ames) tests were performed to verify the above results. In chromosomal aberration tests, CHL cells were incubated with Ace 10, 20 and 40 mg · L-1 for 4 h in the presence or absence of metabolic activation system solution (S9 mix). Methyl methane sulfonate (MMS) 20 mL · L-1 without S9 mix and cyclophosphamide (CP) 12 mg · L-1 with S9 mix served as positive control. The number of chromo?somes in each aberrant metaphase (including fissure, exchange, ring, break and polyploid) was counted and recorded, when the distortion rate less than 5％was considered negative and more than 10％was considered positive. In Ames test, the potential mutagenicity was evaluated using five strains of S. typhimurium ( TA97,TA98,TA100,TA102 and TA1535). They were treated with Ace 5, 25, 125 and 625μg per plate with or without S9 mix and incubated for 48-72 h. When without S9 mix, Dexon 50μg per plate served as positive control for TA97 and TA98, MMS 2.0μL per plate served as positive control for TA100 and TA102, and sodium azide 1.5μg per plate served as positive control for TA1535. When with S9 mix, 2-AF 100 μg per plate served as positive control for TA97, TA98 and TA100, 1, 8-dihydroxyanthraquinone (100μg per plate) served as positive control for TA102 and CP 50μg per plate served as positive control for TA1525. When the number of colonies was at least two-fold that of the negative control, the compound was considered mutagenic. RESULTS Although the Derek and Sarah software predicted that the NPX impurities were not genotoxic, ADMET data showed that Ace could induce chromosomal aberrations. The distortion rate of Ace 40 mg · L-1 was greater than 5％, but less than 10％. The distortion rate of Ace was less than 5％when<20 mg·L-1. Consistent with the results of ADMET, Ace might induce chromosomal aberrations. Ames test results showed that Ace did not signifi?cantly increase the number of bacteria (5-625μg per plate) compared with the negative control. Contrary to the ADMET results, Ace had no mutagenicity. CONCLUSION Ace has potential chromosomal muta?genicity. For life-long usage of NPX, the content of Ace should be reduced from 0.15％of conventional impurities to 0.015％.

BACKGROUNDAtrial fibrillation (AF) is the most common supraventricular arrhythmia in clinical practice. Chronic atrial fibrillation (CAF) is associated with ionic remodeling. However, little is known about the activity of ATP-sensitive potassium current (IK, ATP) during CAF. So we studied the changes of IK, ATP density and allosteric modulation of ATP-sensitivity by intracellular pH during CAF.

METHODSMyocardium samples were obtained from the right auricular appendage of patients with rheumatic heart disease complicated with valvular disease in sinus rhythm (SR) or CAF. There were 14 patients in SR group and 9 patients in CAF group. Single atrial cells were isolated using an enzyme dispersion technique. IK, ATP was recorded using the whole-cell and inside-out configuration of voltage-clamp techniques. In whole-cell model, myocytes of SR and CAF groups were perfused with simulated ischemic solution to elicit IK, ATP. In inside-out configuration, the internal patch membranes were exposed to different ATP concentrations in pH 7.4 and 6.8.

RESULTSUnder simulated ischemia, IK, ATP current density of CAF group was significantly higher than in SR group [(83.5 +/- 10.8) vs. (58.7 +/- 8.4) pA/pF, P < 0.01]. IK, ATP of the two groups showed ATP concentration-dependent inhibition. The ATP concentration for 50% current inhibition (IC50) for the SR group was significantly different in pH 7.4 and pH 6.8 (24 vs. 74 micromol/L, P < 0.01). The IC50 did not change significantly in CAF group when the pH decreased from 7.4 to 6.8.

CONCLUSIONSDuring CAF, IK, ATP current density was increased and its allosteric modulation of ATP-sensitivity by intracellular pH was diminished.

Adenosine Triphosphate ; pharmacology ; Adult ; Allosteric Regulation ; Atrial Fibrillation ; metabolism ; Chronic Disease ; Dose-Response Relationship, Drug ; Female ; Humans ; Hydrogen-Ion Concentration ; Male ; Middle Aged ; Potassium Channels ; physiology

Combined hepatocellular-cholangiocarcinoma (CHC) is a mixed tumor containing elements of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC).Its remarkable histological heterogeneity has been linked to putative hepatic progenitor cell (HPC) origin.However,detailed histological or phenotypic description is rarely documented.In the present study,we reassessed 68 cases previously diagnosed as hepatitis B-related CHCs by immunohistochemistry and double-fluorescence immunostaining,focusing on HPC associated phenotypic observation of intermediate area of the tumor.It was found that tumor cells showed remarkable heterogeneity in intermediate area.Tumor cells with intermediate morphology between hepatocytes and cholangiocytes were oval-shaped and small with scant cytoplasm and hyperchromatic nuclei,arranging in solid nests mostly.By Keratin 7 (K7) staining,it appeared that the nests of tumor cells represented a maturation process from the undifferentiated small cells to mature hepatocytes through the "transitional" cells.Then,these small cells were further confirmed with intermediate phenotype as HPC by exploring immature hepatocellular marker and HPC/biliary markers co-localization.In conclusion,the HPC associated trait in CHC can be interpreted by HPC origin or gain of"stemness" by dedifferentiation.It is still too soon to give a final word that it is innate or acquired signature of HPC associated trait in CHC.

Objective:To preliminarily verify the cross talk between tissue factor/active coagulation factor Ⅶ (TF/FⅦa) and epidermal growth factor receptor (EGFR) pathways in human colon cancer cells in culture.Methods:FⅦa was treated to HT-29 (KRAS-wild type) and LoVo (KRAS-mutant) colon cancer cells to activate TF/F Ⅶa pathway,qRT-PCR and Western blot were used to detect the expressions of amphiregulin (AREG) and epiregulin (EREG),ligands of EGFR on mRNA and protein levels,respectively.After knocking down expression of TF by TF-targeted siRNA transfection,FⅦa was treated and mRNA expressions of AREG and EREG were detected to see whether the FⅦa-induced effects were dependent on TF.Expressions of mRNA of TF and FⅦwere detected by qRT-PCR following the activation of EGFR pathway by treatment with epidermal growth factor (EGF) to HT-29 and LoVo cells.Results:After TF/FⅦa pathway was activated,for HT-29 cells,expressions of AREG (on mRNA level) and EREG (both on mRNA and protein level) were significantly down-regulated versus those of control group,gene expressions of AREG and EREG were 0.55 ± 0.09 vs.0.99 ± 0.09,0.67 ± 0.10 vs.1.02 ± 0.02,protein expressions of EREG were 0.54 ± 0.09 vs.1.04 ± 0.13,all P ＜ 0.05.For LoVo cells,expressions of AREG (both on mRNA and protein level) and EREG (on protein level) were significantly up-regulated versus those of control group,gene expression of AREG were 1.87 ± 0.39 vs.0.93 ± 0.23,protein expressions of AREG and EREG were 3.09 ±0.73 vs.1.11 ±0.21,1.53 ±0.19 vs.0.97 ± 0.23,all P ＜0.05.The regulating effect of AREG and EREG mRNA expression by FⅦa in HT-29 and LoVo cells could both be partly blocked by knocking down TF expression.For HT-29 cells,activation of EGFR pathway induced no significant TF mRNA expression,F Ⅶ mRNA expression was not detected.However,for LoVo cells,activation of EGFR pathway induced significantly higher mRNA expressions of both TF and FⅦ,expressions were 1.53 ± 0.23 vs.1.00 ± 0.23,53.20 ± 6.08 vs.1.00 ± 0.15,all P ＜0.05.Conclusion:In colon cancer cell LoVo,when activated,TF/FⅦa pathway and EGFR pathway could interact through upregulating the other pathway's effectors,and mutant KRAS might play a critical role in the two pathways'cross talk.

Objective To design a VDT operation related upper extremities fatigue detection system using keying duration (KD)as an indicator of fatigue and to execute experimental verification.Methods The system included the software part able to calculate,compare and analyze KD and hardware part able to support normal VDT operations.Subjects finished typing task under controlled condition while the system was running. The flexor digitorum superficialis (FDS), extensor digitorum communis(EDC),extensor carpi radialis(ECR),extensor carpi ulnaris(ECU)muscle fatigue were retrieved by sEMG method and standardized questionnaire. Results As the number of keystrokes increased, KD shortened by 1.3%, FDS MVC% dropped by 22.9%,and EDC MVC% decreased by 47.9%.The perceived level of typing fatigue also increased.Conclusion Results revealed KD's change with fatigue,showing the possibility of using KD as an indicator of fatigue and validating the feasibility and effectiveness of the system design.

Objective To investigate the expression of matrix metalloproteinase 7(MMP-7) mRNA in LOVO cells of colon cancer induced by TF/F Ⅶ a and its signal pathway.Methods We transfected LOVO cells stably with RNAi plasmid targeting to tissue factor to get TFRNAi LOVO cells and detected efficiency of interference in TFRNAi LOVO cells based on Western blot analysis;Expression of MMP-7 was evaluated in LOVO cells treated with 100 nmol/L FⅦa in 0 h、4 h、8 h、12 h、24 h based on RT-PCR and Northern blot.Expression of MMP-7mRNA was determined in quiescent LOVO cells treated with different doses of FⅦa(0 nmol/L、10nmol/L、50 nmol/L、100 nmol/L、200 nmol/L)for 8 h based on Northern blot.Quiescent LOVO cells were treated for 0 h、4 h、8 h、12 h、16 h、24 h with 100 nmol/L FⅦa to evaluate the expression of p-P38;The expression level of MMP-7mRNA induced by 100 nmol/L FⅦa for 8 h in LOVO cells blocked by 10retool SB203580 0.5 h previously and in TFRNAi LOVO cells were measured by Northern blot.Results Northern blot analysis revealed that FⅦa markedly increased the expression of MMP-7mRNA in a time-and dose-dependent manner.Western blot analysis confirmed that FⅦa stimulates p-P38 in a time-dependent manner.SB203580 block 59.2% expression of MMP-7mRNA in LOVO cells induced by TF/FⅦa.In TFRNAi LOVO cells,the expression of MMP-7mRNA induced by TF/FⅦa was 48% less than that in normal LOVO cells.Conclusions TF/FⅦa Complex induces the expression of MMP-7mRNA in LOVO cells in vitro,possibly through P38 pathway.

Acute Kidney Injury ; physiopathology ; Adolescent ; Cardiomyopathies ; pathology ; Crush Syndrome ; physiopathology ; Earthquakes ; Humans ; Male