Aim To study effects of intraduodenal administration of S-doxazosin, R-doxazosin and rac-doxazosin on the carotid blood pressure and urinary bladder function in anesthetized rats. Methods The various parameters of carotid blood pressure, heart rate, vesical micturition pressure, intercontraction interval in anesthetized rats were recorded with an ADInstruments PowerLab/8s data recording and analysis system, and the vesical micturition volume was measured simultaneously. Results S-Doxazosin, R-doxazosin and rac-doxazosin administered intraduodenally decreased the systolic blood pressure, diastolic blood pressure and mean arterial blood pressure significantly in anesthetized rats in a dose-dependent manner. The inhibition of mean arterial pressure by S-doxazosin, R-doxazosin and rac-doxazosin at 1.0 mg?kg-1 was 23.5%?4.6%, 38.5%?8.9% and 42.6%?7.5%, respectively. The ED30 values of decreasing mean arterial blood pressure by S-doxazosin, R-doxazosin and rac-doxazosin were (2.0?0.8),(0.6?0.7) and (0.6?0.5) mg?kg-1,respectively. S-Doxazosin had a weaker inhibitory effect on the carotid blood pressure compared with R-doxazosin and rac-doxazosin, but no significantly different effect was observed between R-doxazosin and rac-doxazosin on the carotid blood pressure. rac-Doxazosin produced a significant inhibition on the heart rate at the dosage from 0.1 mg?kg-1 to 3.0 mg?kg-1 in a dose-dependent manner, but S-doxazosin and R-doxazosin reduced the heart rate only at 3.0 mg?kg-1. S-Doxazosin, R-doxazosin and rac-doxazosin administered intraduodenally decreased the vesical micturition pressure dose-dependently in anesthetized rats. The maximal inhibition of vesical micturition pressure by S-doxazosin, R-doxazosin and rac-doxazosin was 13.4%?5.7%, 14.5%?11.0% and 10.9%?7.6%, and their inhibitory potency on the vesical micturition pressure was not significantly different each other. R-Doxazosin, however, decreased the intercontraction interval and vesical micturition volume significantly compared with S-doxazosin, but S-doxazosin and rac-doxazosin did not significantly affect the intercontraction interval and vesical micturition volume. Conclusion In comparison with R-doxazosin and rac-doxazosin, S-doxazosin administered intraduodenally remains the beneficial action on vesical micturition pressure and relieves the adverse effects on blood pressure, heart rate and intercontraction interval in anesthetized rats.

Objective To evaluate the capability of strain rate imaging(SRI)for monitoring regional systolic deformation and synchronicity of left ventricle after coronary artery bypass graft(CABG)and for evaluating effect of surgery and predicting restenosis.Methods The values of systolic strain rate(SRsys),systolic strain(Ssys)and post systolic strain index(PSI)in 5 segments supplied by left anterior descending coronary artery were measured in study group(60 patients with coronary artery disease)at 1 day before and 10 days,1 month,3 months and 6 months after CABG.Forty healthy participants served as a baseline control group.The regional myocardial function before and after CABG was compared and analyzed.Results The peak values of SRsys and Ssys decreased before CABG in study group.In 52 of the 60 patients,SRsys and Ssys in the graft segments increased gradually and showed statistical significance in most studied segments at 3 and 6 months after surgery.In the above 52 patients,value of PSI increased before CABG and reduced significantly in all analyzed segments at 6 months after surgery.The restenosis of graft artery was suspected in 8 patients by SRI and the positive predictive value was 75%.The diagnosis sensitivity of SRI parameter method was higher than that of 2-dimensional echocardiography and the sensitivity of Ssys was higher than that of SRsys.Conclusions SRI can be used to quantitatively assess the regionsl systolic deformation and synchronicity and monitor the improvement of myocardial function after CABG and determine the effect of surgery and predict restenosis of graft artery.

Objective To evaluate the changes of ventricular synchrony in patients with acute myocardial infarction(AMI)before and after percutaneous coronary intervention(PCI)by speckle tracking imaging(STI).Methods Thirty patients with AMI were examined by traditional echocardiography and STI before and 5 d,1 month after PCI.Myocardial imaging of left ventricular apical long views and parasternal left ventricular short axis views were recorded and stored.The time to peak longitudinal systolic and diastolic strain rate(TS-SRL,TE-SRL)and to peak radial systolic and diastolic strain rate(TS-SRR,TESRR)were measured respectively.The differences of the maximum and minimum systolic and early diastolic peak time(TSL-diff,TER-diff)and the standard deviation(TSL-SD,TER-SD)in 18 longitudinal segments were calculated.And the differences and standard deviation of TS-SRR and TE-SRR(TSR-diff,TSR-SD,TER-diff,TER-SD)were calculated also.These parameters were compared before and after PCI.Results Compared with before and 5 d after PCI,the values of TSL-diff,TSL-SD,TEL-diff and TEL-SD in 1 month after PCI were decreased significantly(P＜0.01).TSR-diff,TSR-SD,TER-diff and TER-SD were decreased also and the differences had statistical significance(P＜0.01).The cardiac synchronized index and LVEF values showed good negative correlation.Conclusions The systolic and diastolic synchrony of left ventricle in AMI patients was abnormal.STI can evaluate left ventricular synchronized function and the changes before and after PCI to assess the effect of PCI.

Objective To investigate the percentage,mature classification and Immune killing function of Vγ9Vδ2T cell in peripheral blood of HCC patients.Methods Peripheral blood mononuclear cells (PBMCs) were isolated from HCC patients (n =25) and healthy donors (n =20) by discontinuous density gradient centrifugation.Proportion,mature and differentiate subtypes and IFN-γ and CD107a expressing of the delta 2 T cells were detect by using flow cytometry,δ2Tcell were selectively cultured with zoledronate and human IL-2.After 12-14 days cells were collected and tested for the second time.Results While the percentage of Vγ9Vδ2Tcell of total T cell in peripheral blood of HCC patients is lower than healthy people before culture (t =4.505,P ＜ 0.001),after augmentation in vitro the proportion increased significantly (t =8.782,P ＜ 0.001),to a level similar to healthy group (t =1.644,P =0.109).There was no statistically significant difference when differentiation subtypes of patient's Vγ9Vδ2Tcell were compared with healthy group before culturing (all P ＞ 0.05),after culture the proportion of Tn,Tcm and Temra decreased [t(Tn) =2.081,t(Tcm) =2.478,t(Temra) =2.953,all P ＜ 0.05],and the proportion of Tem,Tem+ Temra increased [t(Tem) =12.6,t (Tem + Temra) =9.843,all P ＜ 0.001].Cell culture did not alter the proportion of IFN-γ and CD107a secreting Vγ9Vδ2T cells in the peripheral blood in both HCC patients and healthy people (all P ＞ 0.05).Conclusions While the percentage of Vγ9Vδ2T cell of HCC patients in peripheral blood was lower than healthy people,its matured subtypes are similar to those of healthy people,and functions of expressing IFN-γ and CD107a are not different with healthy people.Applying ZOL + IL-2 can amplifyVγ9Vδ2T cells of patients with HCC.

Objective To evaluate left ventricular myocardial function of rabbit after ischemiareperfusion using speckle tracking imaging (STI),and to explore the myocardial protect effects of ischemia postconditioning (I-PostC) on reperfusion injury.Methods 24 Japanese rabbits were divided into ischemiareperfusion group (group Ⅰ) and I-PostC group (group Ⅱ) randomly.The characteristic changes of left ventricular global and regional myocardial strain and twist function of two groups were evaluated quantitatively by STI and compared with pathological results.Results ① Global longitudinal systolic strain rate(GLSrsys),global longitudinal systolic strain (GLSsys) and global longitudinal peak strain(GLSp) decreased in both groups,longitudinal systolic strain rate(SrLsys),longitudinal systolic strain(SLsys) and longitudinal peak strain(SLp) in the lateral wall of left ventricle decreased significantly and negative peak of SrLivr and PSI increased after the left ventricular branch of coronary artery was occluded;The values of Ptw and untwR of left ventricle were smaller.② After the artery was released,GLSp recovered in group Ⅱ,which was not seen in group Ⅰ.The values of SrLsys,SLsys and SLp increased significantly and negative peak of SrLivr and PSI decreased in group Ⅱ.However,only Slsys and SLp rebounded in group Ⅰ.Between the 2 groups,SrLsys andSLp in group Ⅱ were higher than that of group Ⅰ (P＜0.05 or 0.01),and SrLivr was lower compared with group Ⅰ (P ＜0.05).In group Ⅱ,Ptw and untwR changed back to a normal range (P ＜0.05 or 0.01),and no index has changed in group Ⅰ ;Between the 2 groups,Ptw and untwR in group Ⅱ were higher than that of group Ⅰ (P ＜0.05).③ The sensitivity and specificity of GLSrsys,GLSsys,SrLsys,SLsys and Ptw to detect rabbit myocardial infarction were 81.3 ％ and 75.0 ％,62.5 ％ and 81.2％,87.5％ and 87.5％,93.8％ and 75.0％,81.3％ and 68.7％ respectively.Conclusions STI may provide a promising approach to evaluate the global and regional myocardial function.It also can observe the protect effects of I-PostC on myocardial reperfusion injury accurately.

Aim To compare the cytotoxicity of geni-poside (GS)and its metabolite genipin (GP)on hu-man hepatocelluar HepG2 cells and explore the sub-stance and mechanism of hepatotoxicity induced by Fructus Gardeniae.Methods The cytotoxic effect of GS and GP was analyzed by MTT method;the antioxi-dant enzyme activities of manganese superoxide dis-mutase (Mn-SOD),catalase (CAT)and levels of glu-tathione (GSH)were detected by respective kits;the change of intracellular reactive oxygen species (ROS ) was measured by 2′,7′-dichlorofluorescin diacetate (DCFH-DA)staining method;multiparameter cytotox-icity analysis (cell loss,nuclear size and morphologi-cal changes,DNA content,cell membrane permeabili-ty,mitochondrial membrane potential changes,cyto-chrome C release ) were measured simultaneously by high content screening (HCS)assays.Results No cytotoxicity was found in GS (20~1 000 μmol·L-1 ) groups (P>0.05 ),but GP was found to exert obvi-ous cytotoxic effect,and 50μmol·L-1 GP could obvi-ously inhibit HepG2 cell proliferation (P<0.05 ),and the IC50 value was (450.00 ±26.15)μmol·L-1;GS showed no obvious effects on Mn-SOD, CAT, GSH ,ROS (P >0. 0 5 ),GP could significantly decrease the activity of Mn-SOD,CAT and the level of GSH,and obviously increase the content of ROS (P<0.05 or P <0.01 );treatment with 50,500,1 000μmol·L-1 GP resulted in loss of mitochondrial mem-brane potential,cytochrome C release and increased cell permeability (P<0.05 or P<0.01),500,1 000μmol· L-1 GP could also show abvious nuclear con-densation,increased total nuclear intensity and cell loss (P<0.0 1 ).Opposed with GP,GS had no signif-icant effect on the cytotoxic parameters (P>0.05 ). Conclusion GP is the direct substance of hepatotox-icity induced by Fructus Gardeniae,and the mecha-nism might be associated with oxidative stress,mito-chondria injury and apoptosis.

OBJECTIVETo investigate the expression and clinical significance of mismatch repair genes hMLH1 and hMSH2 in sporadic colorectal carcinoma tissues.

METHODSThe expression of hMLH1 and hMSH2 proteins was detected in the 63 sporadic colorectal carcinoma samples by immunohistochemical staining, including tumor tissue, adjacent tissue at 3 cm from the carcinoma, and normal tissue at 10 cm away from the tumor.

RESULTSThe positive rate of hMLH1 protein expression in the 63 normal colorectal tissues, adjacent tissues and sporadic colorectal carcinoma tissues was 95.2%, 85.7% and 81.0%, respectively. The positive rate of hMLH1 protein expression was significantly lower in the tumor than in normal colorectal tissues (P < 0.05). The positive rate of hMSH2 protein in the 63 normal colorectal tissues, adjacent tissues and sporadic colorectal carcinoma tissues were 76.2%, 66.7% and 52.4%, respectively. The positive rate of hMSH2 protein expression was significantly lower in the tumor than in normal colorectal tissues (P < 0.01). The positive rate of hMLH1 protein expression was significantly higher in the tumor tissue of patients aged younger than 60 years (100%) than that in patients ≥ 60 years (75.0%, P < 0.05). The positive rate of hMLH1 protein expression in the tumor tissue accompanied by lymphatic metastasis was 50.0%, significantly lower than that (93.3%) in tumors without lymphatic metastasis (P < 0.05). The positive rate of hMSH2 protein expression in the tumor tissue of patients aged younger than 60 years was 80.0%, significantly higher than that (43.8%) in the cases ≥ 60 years (P < 0.05). The positive rate of hMSH2 protein expression in the tumor tissues with invasion reaching to the intestinal serosa (61.5%) was significantly higher than that (37.5%) in the tumors invading to submucosa or muscular layer (P < 0.05). There was a positive correlation between the expressions of hMLH1 and hMSH2 proteins in the sporadic colorectal carcinomas.

CONCLUSIONThere is a certain loss of expression of hMLH1 and hMSH2 proteins in sporadic colorectal carcinoma, and is correlated with the age of patients, lymphatic metastasis and different depth of cancer invasion. HMLH1 and hMSH2 may be used as a useful laboratory marker in clinical judgement of occurrence and development of sporadic colorectal carcinoma.

Adaptor Proteins, Signal Transducing ; metabolism ; Adenocarcinoma ; metabolism ; pathology ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; metabolism ; Colonic Neoplasms ; metabolism ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; metabolism ; Neoplasm Invasiveness ; Nuclear Proteins ; metabolism ; Rectal Neoplasms ; metabolism ; pathology

Carcinoma, Hepatocellular ; diagnosis ; therapy ; Humans ; Liver Neoplasms ; diagnosis ; therapy ; United States

OBJECTIVETo explore the apoptosis resistance induced by Leptin and its mechanism in breast cancer cells in vitro.

METHODSThe leptin-mediated reduction of docetaxel-induced apoptosis in human breast cancer T47D cells was evaluated by TransAM ELISA, MTT and caspase-9 assay. The leptin-promoted survivin expression was analyzed by Western-blot and RT-PCR. The reversing effect of STAT3 knockdown on leptin-induced survivin upregulation was measured by Western-blot and RT-PCR.

RESULTSLeptin promoted T47D cells proliferation and the inhibitory rate was -63.6%. It reduced docetaxel-induced apoptosis in T47D cells by 31.9%. Leptin at different concentrations promoted survivin protein and mRNA expression in T47D cells. The expression of survivin mRNA was 4.6 fold compared with the T47D cells not treated with leptin(10 nmol/L). The expression of survivin mRNA in T47D cells was 0.55 +/- 0.15 fold after transfected with small interfering RNA (siRNA) of STAT3. The expression of survivin mRNA in STAT3 siRNA group and mock transfected group were 0.56 +/- 0.18 fold and 1.61 +/- 0.22 fold after treated by leptin, respectively. The survivin protein level of T47D mock transfected cells was increased after treated by leptin, but the protein level of T47D transfected with STAT3 siRNA cells were not changed significantly.

CONCLUSIONLeptin/STAT3 signaling is a novel pathway for up-regulation of survivin expression in breast cancer cells.

Apoptosis ; drug effects ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Female ; Humans ; Inhibitor of Apoptosis Proteins ; Leptin ; pharmacology ; Microtubule-Associated Proteins ; genetics ; metabolism ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; STAT3 Transcription Factor ; genetics ; metabolism ; Signal Transduction ; Transfection ; Up-Regulation

BACKGROUND: Because of scaphoid irregular shape and the wrist joint and adjacent bones overlap, so the diagnosis and treatment of scaphoid fracture and treatment became so difficult. Which imaging methods hold highest diagnosis rate, and which kind of surgical approaches with less impact on fracture healing are still under discussion.OBJECTIVE: To review the imaging examinations of scaphoid fracture and the research advance in surgical approaches.METHODS: The first author retrieved CJFD and PubMed databases for the literature addressing the imaging examinations and surgical approaches of scaphoid fracture published from 2005 to 2015 with the keywords of "scaphodl bone, fracture, iconography, surgical approach" in Chinese and English, respectively. The old and repetitive articles were excluded, totally 3021 articles were retrieved. In accordance with inclusion and exclusion criteria, finally 24 eligible articles were included for result analysis.RESULTS AND CONCLUSION: (1) The wrist joint at positions of pronation 60°, supination 45°, oblique and lateral can reveal the scaphoid from different angles on X-ray, which improves the diagnosis rate. At present, CT is the most reliable method, but there is a lack of quantization parameter for evaluating scaphoid fracture, especially for occult fracture. MRI can completely show the structure of scaphoid, even blood supply. Bone scintigraphy possesses a higher diagnosis rate than X-ray and CT examinations. (2) The surgical approaches of scaphoid fracture include volar, dorsal, radiocarpa approaches, but none is ideal. (3) The ideal surgical approach still needs a in-depth study, which can well reveal the scaphoid, achieve good reduction, reduce the damage to the remaining blood supply, confirm the position of scaphoid benifical for internal fixator implantation, and can be minimally invasive and easy to operate.