Objective To study the relationship between IP 3 and detrusor cell contraction mediated by M 3R. Methods [3H]-IP contents of human cultured detrusor cells were detected after stimulated by carbachol,atropine,methoctramine and 4-DAMP respectively. Results [3H]-IP contents increased with carbachol concentration.On the different concentrations (10 -9、10 -8、10 -7、10 -6、10 -5、10 -4 mmol/L )of 4-DAMP,[3H]-IP contents were 3 926.57?273.29、2 780.52?211.09、2436.84?153.62、1 973.22?164.71、1 372.38?141.35 and 1 107.98?920.45 cpm respectively.On the some concertrations of Atropine,[3H]-IP contents were 3 602.69?280.17,2 891.31?207.45,1 983.97?145.74,1 269.57? 105.31,1 106.37?75.23,927.50?77.36/min,respectively.On the same concentrations of methoctramine, the [3H]-IP contents was 4 462.74?360.69、3 938.61?327.13、3 315.45?270.36、3 063.19? 246.79、2927.37?226.45 and 2 836.55?241.63 cpm.This donoted that 4-DAMP and atropine signficantly inhibited the effect of carbachol on PI decomposition(P0.05). Conclusions M 3R is much related to IP 3.

Objective To study the relationship between mutation of rpsL drug-resistant gene in L-forms of Mycobacterium tuberculosis and drug-resistance to streptomycin in pneumoconiosis patients.Methods A total of 52 clinical isolated strains of Mycobacterium tuberculosis L-forms were collected from 97 pneumoconiosis patients.The mutation of rpsL gene was detected by PCR-SSCP,and the drug-resistance to streptomycin was performed by routine antimicrobial susceptibility test(AST).Results The results of drug susceptibility test showed that 26 in the 52 clinical isolated strains were drug-resistant to streptomycin.The streptomycin-resistant rate was 50.00%(26/52).The gene mutation rate of rpsL detected by PCR-SSCP was 40.38%(21/52).The coincidence rate of two experimental results was 80.77%(21/26).Conclusion High detectable rate of streptomycin-resistant strains in Mycobacterium tuberculosis L-forms was found by PCR-SSCP.The application of PCR-SSCP may possess important value for guiding clinical medication of pneumoconiosis patients complicated with tuberculosis among coal workers

To study the relationship between the density of muscarinic receptor (MR) subtype and the occurrence of bladder instability. The rat model of unstable bladder was established, and the density of MR subtype was determined in normal and unstable bladders. The results showed that there were only m 2 RNA and m 3 RNA present in the detrusor of normal and unstable bladders, and m 1, m 2 or m 3 mRNA subtypes were not detected. In the normal bladder, the amount of m 2 RNA (1 67?0 42) was obviously greater than m 3 RNA (0 64?0 19), and the ratio of them was 2 59∶1. In the unstable bladder, the density of both m 2 and m 3 increased to (2 03?0 65) and (1 53?0 46) respectively, and the increase of m 3 was more significant ( P

Objective To study the relationship between muscarinic receptor(MR) subtype density changes and the producing of unstable bladder Methods The rat model of unstable bladder was established and the MR subtype density of control and unstable bladders were defermined by RT-PCR Results There were only m 2RNA and m 3RNA in the detrusor of control and unstable bladders, but no m 1, m 2 and m 3 mRNA, the amount of m 2RNA(1 67?0 42)was larger obviously than m 3RNA(0 64?0 19),the ratio was 2 59∶1 in control group, and the density of both m 2 and m 3 in unstable bladder increased to (2 03?0 65) and(1 53?0 46)respectively, and the increase of m 3 was more significant ( P

Objective: To optimize the infiltration process of Pericarpium Citri Reticulatae (PCR) in Huoxiang Zhengqi Liquid (HZL). Methods: Using the dissolution content of hesperidin as indicator, the infiltration process parameters for PCR such as soaking time, fineness of grind, degree of compaction, infiltration rate, and medicinal infiltration or not were studied, and considering the actual production efficiency, the optimal process conditions were determined. Results: The optimal infiltration process conditions were as follows: PCR was loaded into the extraction tank without soaking (there was no difference between 24 and 48 h of soaking time), spread evenly and compacted properly; The crude medicine fineness was about 0.5 cm × 0.5 cm; The infiltration solvent was 60% ethanol; The infiltration solvent was added to the extraction tank of crude medicines, the volume of solvent can not be too much, just inundating crude medicines; Adding solvent speed and infiltration speed were basically identical; The primary infiltration speed was 1 mL/(min·kg) and the continued infiltration speed was 2 mL/(min·kg). Conclusion: The optimal PCR infiltration process conditions of HZL are determined by evaluating the dissolution content of hesperidin.

Objectives To observe the changes of the detrusor excitability and contractility and to study the mechanism of the unstable bladder. Methods Detrusor strips were obtained from prostectomy patients with benign prostatic hyperplasia. According to the results of urodynamic examination, patients were divided into detrusor instability (DI) and detrusor stability group(DS). Test of mechanical tension and stimulations with electricity and carbachol were performed on the excitability and contractility of the detrusor strips from 8 patients selected from each of the groups in vitro . Results The minimum tension of the detrusor strips when contraction occurred in DI and DS was (0 324?0 132)g and (0 822?0 216)g, respectively. There was significant difference between DI and DS ( P

The oncogenic product of BCR-ABL is an abnormal tyrosine kinase that causes chronic myeloid leukemia (CML). With further research into the pathogenesis of CML, the discovery of compounds that selectively inhibit abnormal BCR-ABL tyrosine kinases is a research focus worthy of attention. The first three generations of BCR-ABL inhibitors are orthosteric inhibitors, which competitively block the binding of ABL protein tyrosine kinase to ATP and prevent it from activating downstream signals. The fourth-generation BCR-ABL inhibitors allosterically inhibit ABL protein tyrosine kinase by binding to the myristoyl pocket, providing greater selectivity and maintaining activity against drug-resistant mutations proteins. Novel drug design strategies such as proteolytic targeting chimera (PROTAC), covalent inhibitors and dual targeting inhibitors also provide new directions for the development of BCR-ABL kinase inhibitors. This paper reviews recent research advances on BCR-ABL kinase inhibitors and discusses drug design strategies for various novel BCR-ABL inhibitors.

ObjectiveTo investigate the feasibility and accuracy of dual energy CT (DECT) in detecting acute myocardial ischemic reperfusion injury in a swine model.Methods Acute myocardial ischemic reperfusion injury model was made by ligaturing the left anterior descending coronary artery (LAD)or the first diagonal artery ( D1 ) of swine heart,the first-pass contrast enhanced DECT was performed.And then pigs were sacrificed,and the hearts were removed,triphenyhetrazolium chloride staining was performed.The CT numbers of non-ischemic and ischemic regions were measured.In the short axis of the left ventricle,the ventricular wall was divided into 17 segments for analysis,segments with myocardial perfusion defect in DECT myocardial iodine maps,DECT ( 140,100 kV,weighted average 120 kV) were determined and compared with histopathology.The sensitivity,specificity and inter-modality agreement of DECT in detecting myocardial injury were calculated.One-way ANOVA test was used to analyze the differences between the CT number and weight of infracted myocardium measured on DECT at 140,100 kV,weighted average 120 kV in ischemic and normal regions.ResultsPartial sparse or defective perfusion in the apical anterior and septal wall were demonstrated in DECT myocardial iodine maps.The CT number of injured myocardium was significantly lower than that of normal myocardium at 140,100 kV,weighted average 120 kV.The sensitivity,specificity of DECT myocardial iodine maps were 85.2％ (23/27),86.2％ (94/109),and Kappa value was 0.62,the sensitivity,specificity at 140 kV were 88.9％ (24/27),92.7％ (101/109),and Kappa value was 0.76,the sensitivity,specificity at 100 kV were 85.2％(23/27),89.0％ (97/109),and Kappa value was 0.67,the sensitivity,specificity at weighted average 120 kV were 88.9％ (24/27),91.7％ ( 100/109),and Kappa value was 0.74.There were no significant differences between the weight of infracted myocardium measured on DECT at 140,100 kV,weighted average 120 kV and histopathological results ( F =0.419,P =0.741 ).ConclusionDECT myocardial iodine maps can detect acute myocardial ischemic reperfusion injury in a swine model and have a good correlation with histopathology.

A 19-year-old female presented with a dark erythematous maculopapule measuring 2 cm in diameter on the left lower limb for more than one year.Physical examination revealed an enlarged cherry-like lymph node in the right inguinal region.Histopathology of the lesion revealed that the normal structure of skin disappeared absolutely,and there was a diffuse infiltrate of medium-sized lymphoid tumor cells with unclear nucleoli.Immunohistochemically,the tumor cells strongly expressed CD4,CD56 and CD123,and partially expressed terminal deoxynucleotidyl transferase (TdT).Flow cytometric analysis of bone marrow aspirates showed that abnormal cells amounted to 59.9％,and were positive for CD123st (strong),human leucocyte antigen-DRst (strong),CD56,CD304 (blood dendritic cell antigen-4),CD7,CD11b,CD33,CD36 and chemokine (C-X-C motif) receptor 4,CD13 (dim),CD4 (partial) and CD117 (partial).Transmission electron microscopy of bone marrow cells revealed that there were massive uniformly sized lymphoid cells with thick processes on cell surfaces,a high nucleus/cytoplasm ratio,centrally located round nuclei occasionally with deep gyrus-like notches,clumped marginated heterochromatin and multiple nucleoli.Moreover,a small amount of cytoplasm was observed in the lymphoid cells with the presence of mitochondria and endoplasmic reticulum arranged in concentric circles,which were characteristic of plasma cells.The features of both dendritic cells and plasma cells were found in the tumor cells through transmission electron microscopy.Based on the above findings,a diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN) was made.

Objective To evaluate the response of the lung tumor xenografts in nude mice to antiangiogenic treatment from perspectives of anatomic,vessel function,cellular and molecular level using the multimodality imaging techniques including optical imaging,dynamic contrast enhanced MRI(DCE-MRI)and diffusion weighted imaging(DWI).Methods The green fluorescent protein(GFP)was transplanted labeled using GFP-expressing NCI-H460 cells.After the transfection of GFP,NCI-H460 cells were implanted subcutaneously into nude mice.Ten days after implantion,12 nude mice whose tumor xenografts grew to 0.5-1.0 cm in the maximum diameter were randomly divided into 2 groups,and injected with phosphate-buffered saline and recombinant human endostatin respectively.Then the nude mice in the two groups underwent optical imaging,DCE-MRI and DWI.The volumes,photon counts,the quantitative MR vessel functional parameters including volume transfer constant(Ktrans),rate constant(Kep),volume of extravascular extracellular space(Ve)and maximum area under the enhancement curve(iAUC),and apparent diffusion coefficient(ADC)values of the tumors were recorded.Then tumors were collected and observed using the transmission electron microscopy and pathology examination,including HE staining,microvessel density(MVD)and the expressions of vascular endothelial cell growth factor(VEGF).The Kep and VEGF expressions in experimental group and control group were compared with x2 text,and other values were compared with t test.The Pearson and Spearman test were used for analyzing the correlation of values in the two groups.Results Seven days after inoculation,the fluorescence signals were detected and grew with the growth of the tumors.On the 7 day after starting therapy,the photon counts of experimental group and control group were(2.51 ± 2.43)× 1010(photon/sec)and(5.77 ± 3.25)× 1010(photon/sec),respectively with no significant differences(t =1.964,P ＞0.05).Two sample t test showed that the tumor volumes in experimental group were smaller than those in control group[(365 ± 56)vs(987 ± 265)mm3,t =0.001,P ＜ 0.01].There was a positive correlation(r =0.673,P ＜ 0.05)between the photon counts and the volumes of the tumors.The mean Ktrans,Kep,Ve and iAUC of experimental group were:(0.055 ±0.012)min-1,0.335(0.184—0.894)min-1,0.297 ± 0.041 and 7.334 ± 3.930,and those for control group were:(0.117 ± 0.027)rin-1,0.417(0.324-1.736)min-1,0.326:±:0.062 and 13.280 ± 4.245.There were significant differences of Krans and iAUC(t =5.155,2.518,P ＜ 0.05)between experimental group and control group.And there was a positive correlation(r =0.715,P ＜ 0.0 1)between the values of iAUC and MVD,but not the expressions of VEGF(r =0.484,P ＞ 0.05).The values of ADC in experimental group were higher than that in control group[(791 ± 38)× 10-6 vs(737 ± 43)×10-6 mm2/s],and there were significant differences(t =-2.299,P ＜ 0.05).Two sample t test showed that the MVD in experimental group were lower than that in control group[(11.9 ± 4.8)vs(19.2 ±4.3)item/hpf,t =2.774,P ＜ 0.05].The VEGF expressions in experimental group were lower than that in control group(x2 =4.000,P ＞ 0.05).It was observed that some cells in experimental group had degenerated and apoptotic signs by the electron microscopy.Conclusions Evaluating the response of lung tumor xenografts to antiangiogenic treatment at anatomical,vessel functional,cellular and molecular level using the multimedality imagings is applicable.And it will be in favour of evaluating the therapeutic effect promptly.