Proton pump inhibitors in clinical use is increasingly common and the drug-induced disease caused by them has an upward trend.Through the retrospective analysis of the retrieved literature,this article provides a reference for the rational use of proton pump inhibitors and reduces the occurrence of related drug-induced diseases.

2000 fold). In bystander effect experiment, the death rate of mixed cells was still over 50% even when they contained only 20% TK+ target cells. Fourteen days after nude mice bearing tumors were treated i.p. with GCV, the mean weight and volume of transfected tumors were less than those of untransfected tumors (P

Objective To describe the echocardiographic and clinical findings of patients with accessory mitral valve(AMV).Methods Four adult patients were diagnosed to have AMV by Doppler echocardiography.Results All the four patients had cardiac murmur but 2 were asymptomatic.Echocardiogram showed that two cases had isolated AMV with significant left ventricular outflow tract (LVOT)obstruction.Another patient was complicated by idiopathic hypertrophic subaortic stenosis and his systolic pressure gradient across the LVOT reduced to normal after taking negative inotropic drugs.The fourth patient was associated with complex congenital cardiac anomalies but without LVOT obstruction.Conclusions AMV may not be very rare as previously reported.An echocardiographic examination Can detect AMV and difierentiate it from other causes of LVOT obstruction.

Objective To study the antagonism of glutathione(GSH) and taurine on acute oxidative damage caused by mercury(Hg). Methods 32 Wistar rats were randomly divided into four groups. The rats of control group were given 0.9% saline by subcutaneous injections. The rats in mercuric chloride (HgCl2) group were subcutaneously injected with 2.5 mg/kg HgCl2. Rats of the other two groups were pretreated with 3 mmol/kg GSH and 4 mmol/kg taurine, respectively and two hours later injected subcutaneously with 2.5 mg/kg HgCl2. Urine creatine and mercury contents were determined; mercury level, contents of GSH, MDA and GSH-Px in liver and kidney were evaluated. Results Compared with the control, urine mercury level, level of mercury in liver and in the renal cortex, contents of GSH, MDA and GSH-Px in kidney in the group treated with 2.5 mg/kg HgCl2 were significantly increased. In the rats pretreated with GSH and taurine, contents of MDA in kidney were significantly decreased compared with those treated with mercury only. The levels of GSH-Px in kidney in the group pretreated with GSH and taurine were significantly higher than that not only in the mercury group but also in the control. Compared with the mercury group, levels of mercury in urine and liver in GSH pretreated group were distinctly reduced. Conclusion Pretreated with GSH and taurine have certain protection for the acute oxidative damage caused by mercury.

As the major pathway mediating specific protein degradation in eukaryotes, ubiquitin-proteasome system (UPS) is involved in various physiological and pathological processes such as cell cycle regulation, immune response, signal transduction and DNA-repair. Deubiquitinases (DUB) maintain the balance of UPS and related physiological processes via reversibly removing ubiquitin from the covalently modified protein substrates, which have been implicated in various disease processes in case of their imbalance expression. Because DUB plays critical regulating roles in the UPS pathway, they may be also the ideal drug targets for severe and intractable human diseases, such as cancer and neurodegenerative disease. With the rapid development of proteomic technology, systematical investigation of specific substrates and interacting proteins of varied DUB via mass spectrometry approach may shed light on these DUB's biological function and regulating roles in the physiological and pathogenic states. In this review, we briefly introduce the characteristics of DUB and summarize the recent application and progresses of proteomics in DUB research.
Humans ; Mass Spectrometry ; Proteasome Endopeptidase Complex ; metabolism ; Proteomics ; Signal Transduction ; Ubiquitin ; metabolism ; Ubiquitin-Specific Proteases ; metabolism

Objective To investigate the metabolism characteristics and the potetial biomarker candidates of osteonecro?sis of the femoral head (ONFH) using metabolomic technology. Methods The femoral head specimens from 23 ONFH patients (25 necrotic femoral heads) and 18 normal femoral heads from femoral neck fracture patients were collected for histopathological examination to confirm the diagnosis of all samples. All the metabolites of bone trabecula were extracted for ultra-high perfor?mance liquid chromatography-MS/MS analyzed. The measured variables was pretreat, and PCA (principal component analysis), PLS?DA (partial least squares?discriminant analysis) and OPLS?DA (orthogonal?partial least squares?discriminant analysis) models were employed to confirm the difference between these two groups after UPLC?MS/MS (ultra?high performance liquid chromatogra?phy?mass spectrometry/mass spectrometry) analysis. At last, the differential variables were screened out by PLS?DA and variate analysis (Kruskal?Wallis H test). The changed metabolites were confirmed by MS and MS/MS aligned in HMDB (human metabolo?mic database) and Massbank. The changed metabolites with the most obviously changed peak abundance, D?arginine, L?proline and L?glutamine, were picked out as the potential diagnostic biomarkers. After binary logistic regression analysis, the combined biomarkers candidates were further analyzed by receiver operating characteristic (ROC) curve to evaluate the significance of the combined biomarkers. Results Significant distinction of metabolites expression mode can be seen in PCA, PLS?DA and OPLS?DA models scoring plots between ONFH and control groups. Twelve changed metabolites in ONFH bone trabeculas were con?firmed by multi?variate statistical analysis and variate statistical analysis. Compared with the femoral neck fracture patients, the in?creased metabolites included D?arginine, L?proline, L?glutamine, creatine, uracil, uridine, LysoPC(20∶4(5Z, 8Z, 11Z, 14Z)), Ly?soPC(16∶0), PC(20∶1(11Z)/18∶3(6Z, 9Z, 12Z)) and PE(P?16∶0e/0∶0). The decreased metabolites were reticulataxanthin and β?cryptoxanthin. According to the change fold of peak abundance and variable weight projection in PLS?DA, the most obviously dif? ferential metabolites were picked out as the biomarker candidates of ONFH. The potential biomarkers candidates were identified as D?arginine, L?proline and L?glutamine. The area under the curve of D?arginine, L?proline and L?glutamine ROC were 0.873, 0.712 and 0.862. The area under the curve of ROC was 0.946 after combining D?arginine, L?proline, L?glutamine using binary lo?gistic regression analysis. Conclusion PCA, PLS?DA and OPLS?DA models were used to find out the differential variables in the metabolites of bone trabeculas in ONFH and femoral neck fracture patients. Twelve metabolites were identified by MS/MS, and 3 obviously changed metabolites, D?arginine, L?proline, L?glutamine, were indicated as biomarker candidates. These 3 obviously changed metabolites showed a good diagnostic significance.

AIM: To find one kind of peptide that will conjugate with ouabain and inhibit its biological function, and provide a new treatment strategy for primary hypertension. METHODS: In this study, ouabain was used as a target to screen ouabain conjugated peptide (OCP) from Ph. D. -7 phage display peptide library. After 3 rounds of bio-panning, the products were identified by ELISA and DNA electrophoresis analysis and sequencing. Peptide was synthesized and analyzed the activity by radioligand binding assay. The inhibitory ratio of cell proliferation was measured by MTT and the cell morphology changing was measured by Hoechst 33342/PI staining. The expression of Na~+-K~+-ATPase α1-subunit and β1-subunit were detected by RT-PCR and immunocytochemistry. The levels of the free intracellular Na~+ in EAhy926 cells were measured by laser confocal microscope. RESULTS: The ouabain conjugated peptide was found out, and it was occupied in 0.64(9/14). The analysis of protein showed that the obtained peptides had no homology with Na~+-K~+-ATPase. The amino acid sequence of synthesized peptide was Arg-Cys-Met-Thr-Ser-Arg-Ser. There was binding activity between OCP and ~3H-ouabain. The MTT assay showed that OCP could reverse the inhibition action of ouabain on vascular endothelial EAhy926 cells in a dose and time-dependent manner. The number of apoptotic cells had significantly decreased detected by Hoechst 33342/PI staining. The results of RT-PCR and immunocytochemistry showed that OCP could inhibit the up-regulated expression of Na~+-K~+-ATPase α1-subunit and down-regulated expression of Na~+-K~+-ATPase β1-subunit induced by ouabain in EAhy926 cells. CONCLUSION: The OCP could reverse the growth inhibition and death induction of ouabain in EAhy926 cells, which would provide the basis for studying the interaction between ouabain and Na~+-K~+-ATPase and explore novel anti-ouabain agents.

Aim To explore the relationship between Mre11/Rad50/Nbs1 ( MRN ) complex focus formation and DNA double-strand breaks( DSBs) caused by cinob-ufagin in human hepatocellular carcinoma HepG2 cells. Methods The Na+,K+-ATPaseα1 subunit expression level in liver cancer tissues was detected by immunohis-tochemistry. After HepG2 cells were treated with 5μmol·L-1 cinobufagin for 6, 12 and 24 h, the drug-in-duced DSBs were assessed by single cell gel electro-phroesis ( SCGE ) , the gene transcription and protein levels of Mrel1, Nbs1, Rad50 and p53 were evaluated by Real time-PCR and Western blot. The cell cycle in parallel was analyzed by flow cytometry. Results The Na+, K+-ATPase α1 subunit expression level in liver cancer tissues was significantly increased compared with the tissue adjacent to carcinoma ( P <0. 05 ) . The 5μmol · L-1 cinobufagin could induce the DSBs in a time-dependent manner (P <0. 05), and it could up-regulate the gene expression levels of Mre11, Nbs1, Rad50 and p53 in HepG2 cells ( P<0. 05 ) . The pro-portions of HepG2 cells in S phase were ( 21. 32 ± 4. 21) % in the control group, and (33. 25 ± 5. 72) %, (56. 72 ± 6. 29) % and (67. 32 ± 9. 42) % in HepG2 cells treated with 5 μmol · L-1 cinobufagin for 6, 12 and 24 h, respectively. The proportions of cells in S phase in cinobufagin groups were significantly increased compared with the control group ( P<0. 05 ) . Conclu-sion Cinobufagin could induce the cell cycle arrest in liver cancer HepG2 cells by activation of Mre11/Rad50/Nbs1 Complex.

Objective To investigate the relationship between expression of nuclear factor kappa B p65 ( NF-κB p65) and hippocampal neuronal apoptosis in acute necrotizing pancreatitis (ANP) rats with brain injury. Methods Sixty-four SD rats were randomized into normal saline group (NS) and ANP group. The ANP rat model was induced by retrograde injection of 4% sodium taurocholate into the pancreaticobiliary duct of SD rats. Nissle stain was used to detect the brain injury. Neuronal apoptosis was determined by TUNEL.NF-κB p65 expression was detected by immunohistochemistry and RT-PCR. Results Hippocampal neuron was absent, karyopyknosis, unclear nucleolus and decreased Nissl bodies were found, the injuries was aggravated with time. The apoptosis index at the 3, 6 and 12 h in ANP group was 10.63 ±0.24, 21.02±0.25, 17.12±0.36, respectively, while they were 0.33±0.19,0.71±0.67, 0.45 ± 0. 33 in NS group, and the difference was statistically significant ( P ＜ 0. 01 ). The expressions of NF-κB p65 mRNA were 0. 63 ± 0.05,1.05 ±0.06,0.92 ±0.05, which were significantly higher than those in the NS group (0.11 ±0.01,0.12±0.01,0.08±0.01,P＜0.05).The chatge of expression of NF±κB p65 protein was consistent with that of NF-κB p65 mRNA. Conclusions The brain injury of ANP rats was highly correlated with neuronal apoptosis at the early and middle phase of ANP, and its mechanism may be related with NF-κB p65 activation.

Objective To assess the radial systolic function of left ventricle(LV) in patients with dilated cardiomyopathy(DCM) by velocity vector imaging(VVI).Methods Sixteen patients with DCM and twenty control subjects were detected by VVI.VVI data were collected from the six basal segments and six mid segments in parastenal LV short axis views.The radial systolic velocity(V) ,strain(ε) ,strain rate(SR),the time to peak systolic velocity(PTV) and the time to maximum strain(PTε) were measured with special software.The differene of the earliest and the latest time to peak velocity(T-max) and the standard deviation of time to peak velocity(T-SD) of 12 segments were calculated.Results Compared to the controlled group,patients with DCM had significantly lower radial V,ε and SR (P ＜0.01) in all the 12 segments,significantly longer PTV and PTε (P ＜ 0.05) in most segments, and significantly larger T-max and T-SD (P ＜0.05).Conclusions VVI is useful to assess the abnormalities in LV radial movement in patients with DCM and could provide more information about regional cardiac function.