Objective To observe the effect of treadmill training on metabotropic glutamate receptor of a middle cerebral artery occlusion model in rat and its underlying mechanisms. Methods Sprague-Dawley male rats of 2 or 3 months old were randomly divided into 3 groups: a sham operation group, an iscbemia-reperfnsion group and a treadmill training group (subject to 2 weeks of training after the ischemia-reperfusion). All the animals were sacri-ficed after 2 weeks of training and their brains were sampled for measurement of the expression level of the striatum mGluR Ⅰ-mRNA, using RT-PCR technique. Results The striatum mRNA of mGluR1 and mGluR5 was signifi-cantly elevated in the ischemia-reperfusion group(P<0.01), but treadmill training significantly suppressed the ele-vation of the expression of mRNA of mGluR1 and mGluR5 (P<0.01). Conclusions Treadmill training can signif-icantly downregulate mGluR Ⅰ-mRNA expression. This might be one of the important mechanisms for inhibition of the excitatory glutamate production.

Objective To observe the protective effect and mechanism of 2,3,5,4 '-tetrahydroxystilbene-2-O-beta-D-glucoside ( THSG) on atherosclerosis in ApoE konck-out mice. Methods A total of 24 ApoE knock-out mice were randomly divided into normal control group (n=8), model control group (HFD, high-fat diet, n=8) and treated group (THSG, 20 mg· kg-1, i. g. , n=8). The atherosclerosic plaque of aorta wall and aorta root were measured by oil red O staining;The expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in human umbilical vein endothelial cells (HUVEC) through C-reaction protein ( CRP) was studied by Western blotting. Results The atherosclerosis plaque in normal control group was not observed. The lipid accumulation decreased in the aorta and the plaque areas in the aortic sinus in THSG treated-group compared with model control group. Moreover, THSG down-regulated CRP-induced LOX-1 expression in HUVEC. Conclusion The atheroscletosis plaque in ApoE knock-out mice was decreased by THSG. The mechanism might be related to the inhibition of the expression of LOX-1 protein.

The microfluidic channels integrated with microring resonator were designed. The salt coalescence on chip surface caused by liquid volatilization in open environment was avoided and only 30 μL of reaction solution was consumed. These channels significantly reduced the experiment cost. The design, fabrication and characterization of a highly sensitive and label-free silicon-on-insulator (SOI) microring optical resonator integrated with the microfluidic channels were demonstrated. The radius of the microring was 5 μm and the straight waveguide with a width of 450 nm was employed in the microring resonator. The microring resonator device had many advantages such as high sensitivity, label-free and real-time detection. Using different concentrations of ethanol solution with known refractive indices, the refractive index detection sensitivity was 76.09 nm/RIU and the volume refractive index detection limit was 5.25×10Symbolm_4 RIU. We also demonstrated the label-free quantitative specific detections of human immunoglobulin G (IgG) solutions using an antibody-modified microring resonator by measuring the resonance wavelength shift resulting from refraction index changes causing by the immobilization of antibodies and specific recognition between antibodies and antigens, respectively. The results showed that the microring optical resonator could real-time monitor the reaction between biological molecules, the resonator could be used in the quantitative detection and biological sensing.

Objective To investigate the association between single nucleotide polymorphisms (SNPs) of ATP-binding cassette B1 (ABCB1),ATP-binding cassette C2 (ABCC2) and solute carrier organic anion transporter 1B1 (SLCO1 B1) genes with high dose methotrexate (HDMTX)-induced toxicity in children with acute lymphoblastic leukemia (ALL).Methods This study was designed as a casecontrol.From September of 2005 to December of 2011,the blood samples were randomly collected from 142ALL patients from Nanjing Children's Hospital,Enzyme-multiplied immunoassay technique (EMIT) was used to measure the plasma concentration of MTX,Seven SNPs in ABCB1 (rs1045642,rs2032582,rs1128503),ABCC2 (rs717620,rs2273697) and SLCO1 B1 (rs4149081,rs11045879) genes were detected by polymerase chain reaction-ligase detection reaction (PCR-LDR).Results A significantly increased risk of MTX-induced toxicity was observed in patients with MTX elimination delay (OR ＝ 2.828,95％ CI:1.217-6.571,P ＜ 0.05).Two SNPs in SLCO1B1,rs4149081 and rs11045879 were linkage disequilibrium (LD) with each other (R2 =0.979,P ＜ 0.05).Multivariate analysis revealed that individuals with SLCO1B1 rs4149081 AA genotype or SLCO1B1 rs11045879 CC genotype showed increased incidence of MTX elimination delay (OR =4.41,95％ CI:1.537-12.654,P =0.042),and the two genotypes were also associated with significantly increased risk of MTX-induced toxicity (OR =4.118,95％ CI:1.135-14.944,P =0.022).No association of MTX elimination delay or MTX-induced toxicity with the other SNPs analyzed was found.Conclusions SLCO1B1 rs4149081 AA or SLCO1B1 rs11045879 CC genotypes might be a risk factor for the susceptibility to MTX-induced toxicity in children with ALL.

Objective To study the relationship of Helicobacter pylori(Hp)infection degree with serum pepsinogen(PG)and the tumor markers related with gastric cancer .Methods Totally 342 cases of health physical check‐up in our hospital from January to June 2015 were selected .13 C‐UBT was performed to evaluate the Hp infection and infection severitys .The level of serum PG was detected by ELSIA and the levels of tumor markers were detected by luminescence immunoassay .Then the results were statistically analyzed with the SPSS statistical software .Results The positive rate of Hp in 342 research subjects was 49 .42% ,and there was no difference between the male and the female groups(P>0 .05) .The level of serum pepsinogen Ⅰ (PGⅠ )and pepsinogen Ⅱ (PGⅡ)in the Hp(+ + )and Hp(+ + + )groups was significantly higher than that in the Hp negative group ,while the PGⅠ /PGⅡ lev‐el was significantly lower than that in the negative group (P<0 .05) .The level of carbohydrate antigen 724(CA724)and carcino‐em‐bryonic antigen(CEA)had the statistical difference between the Hp(+ + + ) group and the Hp negative group(P= 0 .040 ,P=0 .010) .The Pearson correlation analysis displayed that Hp infection was related with PG Ⅰ ,PGⅡ ,PGⅠ /PGⅡ ,CA724 and CEA . There was a positive correlation between PG Ⅱ and CA50)(r=0 .116 ,P=0 .032);there was a negative correlation between PG Ⅰ /PGⅡ and CA50(r= -0 .193 ,P=0 .000) .Conclusion The combined detection of Hp ,PG and tumor markers could be used as one of methods for screening benign and malignant gastric diseases in the healthy physical check‐up population ,which has an important value for the prevention and intervention of related disease occurrence and development .

Objective To investigate the expression and the early diagnostic significance of heat shock protein 70 in acute allograft rejection of liver-transplamed rats. Methods The model of rat orthotopic liver transplantation was made by using a modified "two-cuff technique". The rats were randomly divided into 3 groups. For each group, donors and receptors all included 15 rats respectively. The control group: Wistar to Wistar liver transplantation; The untreated group: SD to Wistar liver transplantation, not receiving any immunosuppressant after liver transplantation; The treatment group: SD to Wistar liver transplantation, receiving intramuscular injection of tacrolimus (FKS06, 2mg kg-1. day-1) after operation. Five rats were executed randomly in every group on the post-transplantation day 3, 5 and 7 and the graft samples were obtained for optical microscopic observation. The expression of HSPT0 in grafts was detected by using immunohistochemical method and RT-PCR. The correlation between acute rejection following liver transplantation and the expression of HSP70 in grafted liver was studied. Results There was no acute rejection examined in the control group. The untreated group showed typical allograft rejection and the rejection activity index (RIA) went up gradually after the operation (P<0.01). The treatment group showed no rejection or borderline allograft rejection. The level of HSP70 was increased transiently after operation, then reduced in the control group (P<0.05). The level of HSP70 in the untreated group was higher than in the control groupand gradually increased with the prolongation of time after transplantation (P<0.01). A significant correlation was found between HSP70 and pathological score in the untreated group (P<0.01). The treatment group showed low levels of HSP70 of all the time. Conclusions The expression of HSP70 in grafts is closely related to the occurrence and development of the acute rejection and can be useful for early diagnosis of acute allograft rejection following liver transplantation.

Objective To develop a rapid donor liver harvesting method in orthotopic liver transplantation in rats,and to study the stability and the success rate of the model.Methods A total of 200 healthy adult male SD rats were randomly divided into two groups: the experimental group(rapid donor liver harvesting transplant group),and the control group(conventional liver transplant group).The operation time,cold(ischemic) time and warm ischemic time of the donor liver, recipient post-transplation liver function and the success rate of the operation between the 2 grous were cpmpared.Results In the control group,the(operation) time of donor harvesting was(33.8?4.2) min,warm ischemic time and cold ischemic time of donor liver was(3.5?1.2) min and(62.0?4.2) min,with a 80% rate of success.The new method reduced the time for donor surgery to(13.1?2.2)min,and reduced the warm ischemic time and cold(ischemic) time of donor liver to 0 min and(38.0?3.1)min respectively,and with a 94% rate of success(all P

Objective To investigate the role of transcriptional-coactivator with PDZ-binding motif( TAZ) in genistein-induced osteoblastogenic differentiation of mouse bone marrow-derived mesenchymal stem cells ( BMSCs) .Methods Mouse BMSCs were cultured in phenol red-freeα-MEM containing osteogenic supplements for inducing osteogenic differentiation.BMSCs were transfected with siRNA-TAZ and treated with genistein.The temporal sequence of osteoblastic differentiation in BMSCs cultures was assayed by measuring alkaline phosphatase activity (ALP) and calcium deposition.The mRNA expression of bone sialoprotein ( BSP) and osteocalcin ( OC) were detected by reverse transcription-polymerase chain reaction(RT-PCR).The binding interaction between TAZ and cbfa1 was identified by co-immunoprecipitation.Results TAZ expression was detected during the induction of osteogenic differentiation, the ALP activity and calcium deposition were significantly decreased in BMSCs which were transfected with siRNA-TAZ.Genistein(0.01-1 μmol/L) exhibited a dose-dependent effect on TAZ expression in mouse BMSCs cultures.Treatment with genistein ( 1 μmol/L ) resulted in increased ALP avtivity and calcium deposition of BMSC cultures as function of time.Genistein(1μmol/L) also promoted the nuclear localization of TAZ and augmented the interaction between TAZ and cbfa1, and by which upregulated cbfa1-mediated gene expression such as BSP and OC.However, the ALP avtivity and calcium deposition, as well as the expression of BSP and OC were not promoted by genistein in BMSCs transfected with siRNA-TAZ.Conclusion These data suggest that the TAZ plays an important role in genistein-induced osteoblastic differentiation of mouse BMSCs cultures.

Objective To investigate the influences of the functional polymorphisms of cytochrome P450 isozymes 2A6 (CYP2A6),2B6 (CYP2B6),2C9 (CYP2C9),and 2C19 (CYP2C19) on plasma concentration of sodium valproate.Methods A total of 131 Chinese children with epilepsy receiving sodium valproate after a period of more than 5 half-time were recruited.The genotypes of CYP2A6 were detected by multiplex polymerase chain reaction (PCR),and the genotypes of CYP2B6,CYP2C9,and CYP2C19 were detected by PCR-ligase detection reaction.Enzyme-multiplied immunoassay technique was used to measure the plasma concentration of sodium valproate.The association between the polymorphisms and the plasma concentration of sodium valproate were analyzed by one-way ANOVA or Student' s t-test.Results Patients were divided into 4 groups according to the genotyping results of CYP2C9 and CYP2C19 (G1:extensive metabolizers in both CYP2C9 and CYP2C19; G2:CYP2C19 intermediate metabolizers; G3:CYP2C19 poor metabolizers; G4:CYP2C9 poor metabolizers),the mean normalized steady-state sodium valproate concentrations were significantly higher in G3 (3.70 ± 0.95) and G4 (4.35 ± 1.48) patients when compared to those in G 1 (2.57 ± 1.30,t =3.056,4.490,both P ＜ 0.01) and G2 (2.76 ± 1.19,t =2.827,4.462,both P ＜ 0.01) patients.The daily doses (mg/d) of sodium valproate received by G3 (19.46 ± 5.20) and G4 (19.30 ±7.67) patients were significantly lower than that of G1 patients(24.10 ±6.97,t =2.359,2.297,both P ＜ 0.05).There were no differences in daily doses or normalized steady-state concentrations of sodium valproate among the CYP2A6* 4 or CYP2B6* 6 genotypic groups.Conclusions The CYP2C9 and CYP2C19 polymorphisms have dramatic effects on the plasma concentration of sodium valproate.The daily doses of sodium valproate in G3 and G4 patients should be lower than usual.

ObjectiveTo study the synergistic effect of p38MAPK and ERK1/2 in bone marrow mesenchymal stem cells (BMSCs), and to explore their influence on osteogenic differentiation in BMSCs cultures. MethodsMouse BMSCs were cultured in phenol red-free α-MEM containing osteogenic supplements (OS) for inducing osteogenic differentiation. The temporal sequence of osteogenic differentiation in BMSCs cultures was assayed by measuring alkaline phosphatase activity (ALP) and calcium deposition gene expression. The activation of p38MAPK and ERK1/2 was detected by western blotting using phospho-specific MAP kinase antibody. BMSCs were treated with the inhibitor of p38MAPK pathway(SB203580) or ERK1/2 pathway (PD98059), and osteogenic differentiation was measured. BMSCs were treated with SB203580 or sodium arsenite(ARS), a strong activator of p38MAPK, and the phosphorylation of ERK 1/2 was measured. BMSCs were treated with PP2A inhibitor, Okadaic acid(OA), the phosphorylation of ERK1/2 and osteogenic differentiation were measured. lmmunoprecipitation was used to test the binding interaction between PP2A and ERK1/2, and the effect of SB203580 on the interaction. ResultsTreatment of BMSCs with osteogenic supplements resulted in activation of p38MAPK and ERK1/2 that coincided with osteogenic differentiation. Inhibition of p38MAPK activation by SB203580, blocked the osteogenic differentiation, whereas inhibition of ERK1/2 activation by PD98059, enhanced the osteogenic differentiation in a dose-dependent manner.SB203580 treatment resulted in increased ERK1/2 phosphorylation. By contrast, ARS treatment resulted in decreased ERK1/2 phosphorylation. Inhibition of PP2A by OA resulted in increased ERK1/2 phosphorylation. OS-induced osteogenic differentiation was also attenuated by PP2A inhibition. Immunoprecipitation confirmed the association of PP2A with ERK1/2 in BMSCs cultures, which was decreased by SB203580 treatment. ConclusionThe present study demonstrates a synergistic effect between p38MAPK and ERK1/2 signaling pathways via PP2A in BMSCs cultures, which may regulate the osteogenic differentiation of BMSCs.