Objective To study the receptors for the axon guidance factor Netrin-4 and whether the known Netrin-1 receptors, DCC and UNC5H1, are coreceptors for Netrin-4. Methods The receptor for Netrin-4 was detected by affinitycytochemistry and in situ staining with the alkaline phosphatase (AP) tagged Netrin-4 fusion protein. The dynamic character of the binding between Netrin-4 and its receptor was evaluated through ligand-receptor binding assay and competitive binding assay. Results In situ staining of AP4-Netrin-4 protein bound to COS7 cells transiently transfected with eukaryotic expression coding DCC and UNC5H1 showed that the Netrin-4 could bind to the transfected cells. Competitive binding assays showed that Netrin-1 could compete with Netrin-4 for the same receptors. Conclusion DCC and UNC5H1 are coreceptors for Netrin-4. However, because the binding affinity of Netrin-4 with its receptor was lower than that of Netrin-1,it could be inferred that there should exist unique receptor(s) for Netrin-4 other than DCC and UNC5H1.

Adult ; Enzyme-Linked Immunosorbent Assay ; Female ; HSP70 Heat-Shock Proteins ; blood ; Humans ; Lead ; toxicity ; Male ; Occupational Exposure

This study aimed to observe changes in the hydrogen sulfide (H2S) system in the blood and liver tissue of rats with hepatic cirrhosis at different stages by studying the effect of H2S on the course of hyperdynamic circulation in rats with hepatic cirrhosis.H2S concentration in the blood from the portal vein and inferior vena cava of hepatic cirrhosis rat model induced with carbon tetrachloride was detected on the 15th,30th,and 52nd day.The expression of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) protein,and CBS and CSE mRNA in the liver was detected by immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR),respectively.The results indicated that H2S concentration in the blood from the portal vein and inferior vena cava of rats with hepatic cirrhosis was significantly lower than that in the control group.H2S was gradually decreased with the development of the disease and significantly lower in the blood from portal vein than in the blood of inferior vena cava at the mid-stage and the late stage groups.The expression levels of CBS and CSE protein,and CBS and CSE mRNA in the livers with hepatic cirrhosis at different stages were all higher than those in the control group,and the expression gradually increased with the development of the disease.The expression of CBS was lower than CSE in the same stages.The results indicated that the CSE mRNA was expressed predominantly in the cirrhosis groups as compared with CBS rnRNA.Among experimental rats,the H2S system has an important effect on the occurrence and development of hyperdynamic circulation in rats with hepatic cirrhosis.This finding adds to the literature by demonstrating that H2S protects vascular remodelling in the liver,and that CSE is indispensable in this process.

OBJECTIVETo investigate the spontaneous YMDD mutation rate.

METHODSSerum samples collected from 196 untreated chronic HBV patients were detected by primer-specific real-time PCR.

RESULTSAmong 196 patients, spontaneous YMDD variants were detected in 21 subjects (20 YVDD mutants and 1 YIDD mutant). YMDD variants account for more than 50%, 25% to 50%, 9% to 25% of total virus load in 1, 5 and 15 patients, respectively. Gender, age, HBeAg status, serum viral load, the state of disease and duration of infection were not associated with spontaneous YMDD mutation. Genotype B had higher spontaneous YMDD rate than genotype C (20.00% vs 7.38%, x(2) = 6.28, P < 0.05).

CONCLUSIONSpontaneous YMDD variants exist in chronic hepatitis B patients, Genotype B is associated with higher spontaneous YMDD rate.

Adolescent ; Adult ; Aged ; DNA Primers ; DNA, Viral ; analysis ; blood ; genetics ; Female ; Genotype ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; virology ; Humans ; Male ; Middle Aged ; Mutation ; Polymerase Chain Reaction ; methods ; Sensitivity and Specificity ; Viral Load ; Young Adult

Objective To investigate the effects of pioglitazone on glucose metabolism,circulating resistin and adiponectin concentrations,and tissue resistin levels in rats with insulin resistance induced by free fatty acid (FFA).Methods A hyperinsulinaemic-euglycaemic clamp and[3-~3H]-glucose tracing technique were used in awake rats.Insulin-mediated peripheral and hepatic glucose metabolism,plasma resistin and adipenectin levels, resistin levels in tissues were assessed by hyperinsulinaemic-euglycaemic clamp with elevation of FFA by lipid infusion over 4 h in rats pretreated with or without pioglitazone.Results During steady-state of clamp,there was a significant increase in plasma FFA in lipid-infused group(L group)and pioglitazone-pretreated lipid-infused group(P/L group)compared to control rats(P＜0.01).The glucose infusion rate(GIR)in P/L group was significantly reduced as compared with controls[(20.6?0.9 vs 33.6?1.5)mg?kg~(-1)?min~(-1),P＜0.01], whereas the GIR was lower in L group than in P/L group[(12.6?0.8 vs 20.6?0.9)mg?kg~(-1)?min~(-1),P＜0.01].As compared with baseline,the hepatic glucose production(HGP)was significantly suppressed by 85% [(18.3?2.1 vs 2.7+2.4)mg?kg~(-1)?min~(-1) and (17.5?2.6 vs 2.6?1.0)mg?kg~(-1)?min~(-1),both P＜0.01]during the hyperinsulinaemic clamp in control and P/L groups.The suppressive effect of insulin on HGP was significantly blunted in L group[(17.3?2.1 vs 15.8?1.5]mg?kg~(-1)?min~(-1)].The rate of glucose disappearance(G_(Rd))was reduced in L group and P/L group compared with controls(P＜0.01).Baseline plasma resistin level was lower in P/L group than that in the controls[(7.8?1.3 vs 29.1?3.1)?g/L,P＜0.01].After lipid infusion,plasma resistin levels significantly increased in P/L group,but remained lower than that of L group [(18.1?3.8 vs 47.0?2.2)?g/L,P＜0.01].Baseline adiponectin level was higher in P/L group than those in the controls and L groups[(3.9?0.2 vs 2.8?0.1 and 2.6?0.2)mg/L,P＜0.01].After clamp,plasma adiponectin levels were decreased in L group and L/P group compared with baseline(both P＜0.05).In addition, the resistin level in the liver of P/L group decreased compared with the controls and L groups(both P＜0.05), whereas significantly increased in the muscle of L group.Conclusion Lipid infusion induces an acute insulin- resistance in vivo.Pioglitazone pretreatment partly prevents FFA-induced insulin resistance possibly by changing resistin and adiponectin levels.

The purpose of the present study is to explore the protective effects of sodium butyrate (SB) pretreatment on concanavalin A (Con A)-induced acute liver injury in mice. The model animals were first administered intraperitoneally with SB. Half an hour later, acute liver injury mouse model was established by caudal vein injection with Con A (15 mg/kg). Then, levels of serous alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using standard clinical method by an automated chemistry analyzer, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured by ELISA, and pathological changes in hepatic tissue were observed by using HE staining and light microscopy. The expression and release of high-mobility group box 1 (HMGB1) were assessed by using reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and ELISA. The results showed that the pretreatment of SB significantly protected Con A-treated mice from liver injury as evidenced by the decrease of serum ALT, AST (P < 0.01) and reduction of hepatic tissues necrosis. SB also decreased levels of serous TNF-α and IFN-γ (P < 0.01). Furthermore, the expression and release of HMGB1 were markedly inhibited by SB pretreatment (P < 0.05 or P < 0.01). These results suggest that the attenuating effect of SB on Con A-induced acute liver injury may be due to its role of reducing the TNF-α and IFN-γ production, and inhibiting HMGB1 expression and release.
Alanine Transaminase ; metabolism ; Animals ; Aspartate Aminotransferases ; metabolism ; Butyric Acid ; pharmacology ; Chemical and Drug Induced Liver Injury ; drug therapy ; Concanavalin A ; adverse effects ; Disease Models, Animal ; HMGB1 Protein ; metabolism ; Interferon-gamma ; metabolism ; Liver ; pathology ; Mice ; Tumor Necrosis Factor-alpha ; metabolism

Objective To understand the present situation of the chronic schistosomiasis patients'knowledge,attitude and practice on schistosomiasis control in Nanchang City. Methods The knowledge,attitude and values on schistosomiasis control of 523 chronic schistosomiasis patients in Nanchang County,Jinxian County and Xinjian District in the Poyang Lake District were investigated with questionnaires. And the accuracy rates of the knowledge,attitude and practice among the patient groups of different counties,genders,age groups,occupations and educational levels were analyzed. Results The accuracy rates of the knowledge,attitude and practice of patients on schistosomiasis control were 95.76%,82.80%,and 81.73% in Nanchang County;91.37%,93.32%,and 76.48%in Jinxian County;88.25%,67.56%,and 49.40%in Xinjian District. In the accuracy rates of knowledge,attitude and practice,the differences among the three counties (districts) were statistically significant (χ2=57.511-301.378,all P<0.05). Conclusions The accuracy rates of chronic schistosomiasis patients'attitude and prac-tice on schistosomiasis control in Nanchang City remain low. Therefore,the intensity of attitude and practice intervention should be strengthened in the Poyang Lake District in order to enhance the self-protection awareness of the patients.

OBJECTIVETo investigate the expression of microRNA-155 and microRNA-146a in the CD19(+) B cells of chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), splenic marginal zone lymphoma (SMZL), and to analyze its clinical significance.

METHODSPeripheral blood (PB) (78 cases) and bone marrow (BM) samples (9 cases) from 53 CLL patients, 13 MCL patients, 19 SMZL patients, and 12 healthy donors were collected. Mononuclear cells were isolated and B cells were purified with a CD19(+) magnetic-bead system. Total RNA was extracted from purified CD19(+) cells and microRNAs expression were measured using the TaqMan microRNA quantitative PCR. The results combined with the clinic data of patients were analysed.

RESULTS(1) The expression of microRNA-155 in CLL (4.49 ± 0.83) was significantly higher than in MCL (3.83 ± 0.45) and SMZL (3.80 ± 0.61) (P < 0.05); (2) The level of microRNA-146a in SMZL (3.81 ± 0.59) was significantly higher than in CLL (2.58 ± 0.90) and MCL (2.27 ± 0.88) (P < 0.01); (3) The level of microRNA-155 was significantly higher in IgVH unmutated patients than in mutated patients in CLL (P = 0.012); (4) The microRNAs expression had no statistical difference between two prognostic groups in CLL.

CONCLUSION(1) The expression of microRNA-155 and microRNA-146a is different in malignant lymphoproliferative disorders (LPD); (2) Deregulation of the microRNAs expression might play a critical role in the pathogenesis and prognosis in the LPD.

B-Lymphocytes ; metabolism ; Case-Control Studies ; Chronic Disease ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; pathology ; Lymphoproliferative Disorders ; genetics ; pathology ; MicroRNAs ; metabolism

BACKGROUNDP-wave dispersion (PWD) is a useful predictor of paroxysmal atrial fibrillation (AF). The effect of cardiac resynchronization therapy (CRT) on PWD and the prognostic implications of the improvement in PWD remain undefined. The aim of the study was to explore the clinical significance of the improvement of PWD after CRT.

METHODSElectrocardiographic studies were performed before and three months after CRT in 81 patients (57 men and 24 women; age (60.5 ± 11.2) years) with standard CRT indication but no history of AF. A significant improvement of PWD (PWD responder) was defined as a relative decrease ≥ 20% from baseline PWD. The primary endpoints were new-onset AF detected by electrocardiogram (ECG) or CRT.

RESULTSAfter (30.6 ± 7.5) months of follow-up, PWD responders (n = 43) had a significantly lower incidence of AF than did PWD nonresponders, 12% vs. 29% (P < 0.001). In Cox proportional hazard analysis, PWD responders was the only predictor of lower risk of new-onset AF (HR 0.33, 95% confidence interval 0.12 - 0.96, P = 0.033).

CONCLUSIONImprovement of P-wave dispersion after CRT was associated with a lower incidence of AF, which may be related to the significant improvement in left ventricular systolic function and the reverse modeling of the left atrium.

Adult ; Aged ; Atrial Fibrillation ; prevention & control ; Cardiac Resynchronization Therapy ; Echocardiography ; Electrocardiography ; Female ; Heart Failure ; physiopathology ; therapy ; Humans ; Male ; Middle Aged

OBJECTIVETo investigate the effects of 11, 12-epoxyeicosatrienoic acid (11, 12-EET) preconditioning and postconditioning on Ca(2+)-handling proteins in myocardial ischemia/reperfusion (IR) injury in rats and reveal the effects and mechanism of 11, 12-EET on cardioprotection. METHODS The IR injury model was built by stopping perfusion for 40 minutes followed by reperfusion for 30 minutes. The isolated Langendorff-perfused rat hearts were divided into 4 groups: control group, IR group, EET preconditioning (Pre-EET) group and EET postconditioning (Post-EET) group. The computer-based electrophysiological recorder system was used to measure the changes of the maximal rate of pressure increased in the contraction phase (+dp/dt(max)), the maximal rate of pressure decreased in the diastole phase (-dp/dt(max)), the left ventricular end diastolic pressure (LVEDP) and the difference of left ventricular pressure (delta LVP). The activity of Ca(2+)-ATPase in sarcoplasmic reticulum was measured with colorimetric method. Reverse transcription-polymerase chain reaction was used to assess the gene expression of C(a2+)-handling protein [sarcoplasic reticulum Ca(2+)-ATPase (SERCA), phospholamban (PLB), ryanodine receptor type 2 (RyR,), and 1, 4, 5-trisphosphate inositol receptor type 2 (IP3 R2) ] mRNAs level.

RESULTSCompared with IR group, the myocardial functions, the value of Ca(2+)-ATPase, and the expressions of IP3 R2 mRNA were significantly increased and the expression of PLB mRNA was significantly decreased in both Pre-EET group and Post-EET group (P < 0.05, P < 0.01). And the expression of SERCA mRNA was significantly increased in Pre-EET group (P < 0. 05). However, no significant differences were detected between Pre-EET and Post-EET groups. Moreover, the expression of RyR2 mRNA was not significantly different among all groups.

CONCLUSIONS11, 12-EET preconditioning and post-conditioning can protect myocardium from IR injury by elevating the activity of Ca(2+)-ATPase in sarcoplasmic reticulum, up-regulating the expression of IP3 R2 mRNA, and down-regulating the expression of PLB mRNA. Moreover, up-regulating the expression of SERCA mRNA maybe one of mechanisms of 11, 12-EET preconditioning on cardio protection against IR injury.

8,11,14-Eicosatrienoic Acid ; analogs & derivatives ; pharmacology ; Animals ; Calcium-Binding Proteins ; drug effects ; metabolism ; Inositol 1,4,5-Trisphosphate Receptors ; drug effects ; metabolism ; Ischemic Preconditioning, Myocardial ; methods ; Myocardial Reperfusion Injury ; metabolism ; prevention & control ; Rats ; Ryanodine Receptor Calcium Release Channel ; metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; drug effects ; metabolism