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 probe the most effective method for the diagnosis of early renal pelvic cancer. Methods Ultrasound, introvenus urogram (IVU), retrograde pyelography, CT, magnetic resonance urography and transurethral ureteropeyloscopy were performed, and the accuracy rate was evaluated. Results The accuracy rate of IVU, retrograde pyelography, CT, transurethral ureteropeyloscopy, MRU and ultrasound were 89%, 94%, 80%, 50%, 40% and 22% respectively. Conclusions IVU and retrograde pyelography are the common and necessary diagnostic methods for early renal pelvic cancer. Transurethral ureteropeyloscopy is an invasive method and used as a final method when other methods fail to identify the disease.

AIM: To investigate the inhibitory effect of L-carnitine on high glucose-induced apoptosis of human aortic endothelial cells (HAECs) and the molecular mechanisms.METHODS: The apoptosis of HAECs was induced by high-glucose incubation.HAECs were treated with L-carnitine at different concentrations (50, 100 and 200 μmol/L).The cell viability was measured by MTT assay.The cell apoptosis was assessed by Hoechst 33258 staining and flow cytometry.Colorimetric method was employed to detect the caspase-3 activity in the HAECs.The protein expression and phosphorylation levels were determined by Western blot.RESULTS: High-glucose incubation dramatically decreased the cell viability and induced apoptosis.The protein kinase R-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme-1 (IRE1) and activating transcription factor 6 (ATF6) signaling pathways of endoplasmic reticulum stress were activated to induce cell apoptosis via down-stream caspase-4/3 cascade.However, L-carnitine treatment significantly attenuated the cell apoptosis and increased the cell viability in a concentration-dependent manner.L-carnitine also significantly suppressed endoplasmic reticulum stress and ATF6 signaling in high glucose-incubated HAECs without attenuating PERK and IRE1 signaling.The expression of site-1 protease (S1P) and site-2 protease (S2P) was inhibited by L-carnitine treatment, thus decreasing pro-apoptotic factor ATF6 p50 produced by ATF6 cleavage.CONCLUSION: L-carnitine inhibits high glucose-induced apoptosis of HAECs by inhibiting ATF6 signaling.

Objective To identify predictors of prescription initiation and persistence of warfarin in non-valvular atrial fibrillation ( NVAF ) patients with high risk of stroke ( CHA2 DS2-VASc≥2 ) . Methods NVAF patients consulted in our hospital from Aug , 2011 to Apr, 2015 were enrolled.Patients who underwent radiofrequency catheter ablation were excluded . Patients were divided into two groups (warfarin group and non-warfarin group).Logistic regression was used to estimate the predictors of initiation warfarin prescription.Kaplan-Meier survival and Cox proportional hazards model was performed to determine rate of warfarin persistence and its associated factors .Results A total of 622 AF patients were enrolled and 490 patients with CHA2DS2-VASc≥2.Ten patients lost follow up and 480 patients were followed up with a mean follow-up period of ( 40.0 ±11.55 ) months.Of which 245 NVAF patients ( 51%) had a warfarin prescription.Patients with ischemic stroke ( OR 2.447 , 95%CI 1.435-4.171 , P=0.001 ) , heart failure ( OR 2.009 , 95%CI 1.084-3.724 , P=0.027 ) and persistent AF ( OR 2.231 , 95%CI 1.448-3.437 , P=0.0001 ) had a higher likelihood of warfarin prescription .Anemia ( OR 0.479 , 95%CI 0.238-0.964 , P=0.039), concommitant Traditional Chinese Medicine (TCM) use (OR 0.638, 95%CI 0.456-0.891, P=0.008 ) and longer distance to hospital ( OR 0.759 , 95%CI 0.610-0.945 , P=0.014 ) decreased the likelihood of warfarin prescription . One hundred and seventy-six ( 71.8%) warfarin users continued persistent therapy and the overall proportion of warfarin persistence was 78.3% for one year , 71.0% for 3 years.Seventy-six existing warfarin users continued the warfarin therapy (80%, 76/95),one hundred new users showed persistence to therapy ( 66.7%, 100/150 ) .Warfarin use before enrollment significantly increased warfarin persistence than new prescription ( P =0.008 ) .Variables associated with higher discontinuation were new prescription ( HR 1.786 , 95% CI 1.029-3.100 , P=0.039 ) , TCM use ( HR 1.687 , 95%CI 1.201-2.37 , P=0.003 ) and longer distance to hospital ( HR 1.446 , 95% CI 1.121-1.865, P=0.005).Conclusions In anticoagulation clinic, concommitant TCM use, distance to hospital and other factors were associated with warfarin initiation prescription and persistence .Identifying factors associated with warfarin treatment could help in developing adherence of patients .

Objective To investigate the correlation between procalcitonin (PCT) and infarct related artery (IRA) spontaneous recanalization (SR) in patients with ST-segment elevation myocardial infarction (STEMI), and to investigate the value of PCT in predicting SR. Methods A retrospective study was conducted. A total of 263 STEMI patients who received emergency coronary angiography from January 2013 to April 2016 in cardiology department of Gansu Provincial Hospital were retrospectively included. Depending on the thrombolysis in myocardial infarction trial (TIMI) grade, the patients were divided into two groups, SR group (TIMI 2-3 grade) and non-SR group (NSR group, TIMI 0-1 grade). The baseline characteristics, serum PCT, high sensitivity C-reactive protein (hs-CRP) and biochemical makers before primary percutaneous coronary intervention (PCI) were compared. According to the value of PCT, the patients were divided into four quartile groups. SR rate of every groups were compared. Multiple logistic regression analysis was used to determine the independent predictor of SR. Receiver operating characteristic (ROC) curve was plotted to assess the diagnostic value of PCT for SR. Results In 263 STEMI patients, SR occurred in 77 patients and SR rate was 29.3%. There were no statistical differences in gender, age, body mass index (BMI), past medical history and IRA between the two groups, indicating that the baseline characteristics were matched. Compared with NSR group, utilization rate of the statins were significantly higher (35.1% vs. 22.6%, P < 0.05), the value of PCT, hs-CRP, uric acid (UA) in SR group were significantly lower [PCT (μg/L): 0.059±0.036 vs. 0.103±0.048, hs-CRP (mg/L): 3.07±4.13 vs. 5.93±7.80, UA (mmol/L): 321.4±77.4 vs. 354.2±114.1, all P < 0.05]. The quartile value of PCT were < 0.058, 0.058-0.078, 0.079-0.110, > 0.110 μg/L. SR rate were 48.5% (32/66), 29.9% (20/67), 26.9% (18/67) and 11.1% (7/63), respectively. SR rate of Quartile 1 was significantly higher than the other three groups (all P < 0.05). It was shown by multiple logistic regression analysis that PCT [odds ratio (OR) = 0.432, 95% confidence interval (95%CI) = 0.108-0.863, P = 0.016], hs-CRP (OR = 0.708, 95%CI = 0.516-0.905, P = 0.037) were independent predictors for SR. The area under the ROC curve (AUC) of PCT for predicting SR was greater than that of hs-CRP [0.784 (95%CI = 0.721-0.847) vs. 0.686 (95%CI = 0.619-0.753), P < 0.05]. When the cut-off value of PCT was 0.067 μg/L, the sensitivity was 81.6%, and the specificity was 66.7%. Conclusion PCT was independent predictor of SR, which has a power value in predicting IRA recanalization in patients with STEMI.

Aim To investigate the effect of ouabain and cinobufogenin on cell proliferation,apoptosis and cell cycle on HepG2,and explore their molecular mechanism.Methods The anti-proliferative effect on HepG2 cells was determined by MTT assay.The HepG2 cells were stained with Hoechst 33342,and its morphological changes were observed under fluorescence microscope;The cell cycle was measured by flow cytometry.The Cyclin A1,CDK 2,PCNA and p21~(CIP1) expression levels of HepG2 cells treated with ouabain and cinobufogenin were dectected in mRNA and protein by Real time PCR and Western blot.Results Ouabain and cinobufogenin could inhibit cell proliferation on HepG2 cells,and the inhibitory effects were in time and dose dependent manners.The HepG2 cells treated with ouabain and cinobufogenin showed the typical morphological features of apoptosis.Cell cycle analysis showed that the S phase of HepG2 cells treated with ouabain and cinobufogenin increased significantly compared with the control group.Real-time quantitative PCR and Western blot results showed that ouabain and cinobufogenin could down-regulate Cyclin A1,CDK 2,and PCNA expressions(P<0.05)and up-regulate p21~(CIP1) expression(P<0.05).Conclusion Nα~+,K~+-ATPase inhibitor has the anti-proliferative effect on HepG2 cells and induce apoptosis and S phase arrest.These effects might be related with proteins associated with cell cycle closely.

In this paper is used the rough set theory to deal with the information contained in electrocardiographic waveforms and to find out the correlation between coronary heart disease (CHD) and the selected indices in electrocardiographic lead I. The principles of attribute reduction are applied, the redundancy of a decision-making table is reduced, and the important characters and diagnostic rules are extracted. The real case analysis shows that clear and concise diagnostic rules can be established by using rough set theory, which can be helpful to the clinical diagnosis of CHD.
Algorithms ; Coronary Disease ; diagnosis ; Decision Making, Computer-Assisted ; Electrocardiography ; methods ; Humans ; Predictive Value of Tests ; Signal Processing, Computer-Assisted

The stable isotope labeling by amino acids in culture (SILAC) based quantitative proteomics serves as a gold standard because of the high accuracy and throughput for protein identifications and quantification. In this study, we discussed the application of SILAC technology in mammal model, and developed quantitative internal standard for comparative proteomics of disease model. The C57BL/6J mice fed by special diet containing the 13C6-Lysine and bred F2 generation. We identified and analyzed total proteins of 9 mice tissues of F2 generation, including brain, lung, heart, stomach, intestine, liver, spleen, kidney, and muscle. Quantitative analysis information could evaluate the mice and different tissues' labeling efficiency. Liver was the most efficient, brain the least, and the labeling efficiency were 96.34%±0.90% and 92.62%±1.98% respectively. The average of the labeling efficiency of F2 generation was 95.80%±0.64%, which met the international standard (≥ 95%) for SILAC quantitative proteomics effective study. SILAC technology was successfully extended to mammalian model system, which will provide powerful tools for the mechanism study of the pathophysiology process with mouse model.
Amino Acids ; chemistry ; Animals ; Diet ; veterinary ; Isotope Labeling ; Lysine ; chemistry ; Mice ; Mice, Inbred C57BL ; Proteins ; chemistry ; Proteomics ; methods

Objective To compare the clinical efficacy of nasal intermittent positive pressure ventilation (NIPPV) and heated humidified high flow nasal cannula (HHHFNC) in the treatment of respiratory distress syndrome (RDS) among low-birth-weight premature infants.Method From May to December 2015,low-birth-weight premature infants with RDS who were born and treated in our hospital were randomly assigned into NIPPV group and HHHFNC group according to their initial ventilation mode.The incidence of initial treatment failure,the usage of pulmonary surfactant (PS),the parameters of respiratory support treatment and the incidence of complications were analyzed.Result A total of 70 cases with grade Ⅰ ～ llⅢ of RDS were included,including 33 males and 37 females.The birth weight ranged from 1 020 to 2 450 g,with a average of (1 845 ± 475) g.NIPPV and HHHFNC group each had 35 cases.No significant differences existed between the two group in the following items:the rate of mechanical intubation within 72 h (5.7％ vs.11.4％),use of PS (0％ vs.8.6％),incidence of severe apnea (11.4％ vs.14.3％),pneumonia (11.4％ vs.14.3％),the duration of invasive mechanical ventilation [76.3 (30.8,150.4) h vs.97.6 (56.2,142.6) h],non-invasive ventilation [65.0 (43.0,119.0) h vs.96.0 (65.0,134.0) h] and the duration of oxygen therapy [154.0 (47.0,340.0) h vs.148.0 (72.0,327.0) h,it was no (P ＞ 0.05).Also,no significant differences in the incidence of bronchopulmonary dysplasia,necrotizing enterocolitis,retinopathy of prematurity,patent ductus arteriosus,intra-ventricular hemorrhage,nose injury,pneumothorax between the two groups.Conclusion As an initial respiratory support for the treatment of low-birth-weight RDS preterm infants,HHHFNC has similar efficacy and safety with NIPPV,and further clinical research is needed.

9-nitro camptothecin (9-NC) loaded amphiphilic copolymer micelles were prepared with solvent evaporation method. The effects of temperature, distilled water volume, stirring rate, and drug input amount on the size and drug content of micelles were further discussed. As a result, well dispersed spherical micelles with drug content of 4.9 percent and 50 -70 nanometers in diameter were achieved with the following preparation conditions: water bath temperature 60 degrees C , distilled water amount 16 ml, stirring rate 6 500 r/min, and drug input amount 1.2 mg. 9-NC release profiles in vitro illustrated that drug release from micelles included initial burst release and following controlled release. The release rate was decreased with the increase of drug content.
Antineoplastic Agents ; administration & dosage ; chemistry ; Camptothecin ; administration & dosage ; analogs & derivatives ; chemistry ; Delayed-Action Preparations ; chemical synthesis ; chemistry ; Drug Carriers ; chemistry ; Drug Compounding ; Humans ; Micelles ; Nanoparticles ; Particle Size ; Polymers ; Solubility