Proteio degradation via ubiquitin-proteasome system(UPS) is carried out with a wide variety of signallingpathways,from cell cycle and transcription to development.The mass spectrometry-based proteomics techniques are powerful tools in the research of UPS.The recent advance in the study of UPS by proteomics techniques is briefly reviewed.

Objective: To observe the clinical efficacy and safety of the combination therapy of sitagliptin and irbesartan in the treatment of early diabetic nephropathy.Methods: Totally 49 cases of initial diagnosed diabetic nephropathy were randomly divided into the observation group (25 cases) and the control group (24 cases).On the basis of diabetic diet, health education and regular hypoglycemic drugs, the control group was treated with irbesartan tablets, 150 mg, po , qd, and on the basis of the control group, the observation group was treated with sitagliptin tablets 100mg, po , qd.All the patients were treated for 3 months.The fasting blood glucose (FBG), postprandial blood glucose (PBG), glycosylated hemoglobin (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), urinary microalbumin (mAlb) and body massindex(BMI) were compared between the groups before and after the treatment.Results: After the treatment, FBG, PBG, HbA1c, SBP, DBP and mAlb in the observation group were significantly lower than those before the treatment (P＜0.05).Hypoglycemia occntrredin in one patient in the observation group.There were no significant changes in FBG, PBG and HbA1c in the control group (P＞0.05), and SBP, DBP and mAlb decreased significantly (P＜0.05).After the treatment, the decrease of FBG, PBG, HbA1c and mAlb in the observation group was more significant than that in the control group, and the difference was statistically significant (P＜0.05).The decrease of blood pressure between the groups was not statistically significant (P＞0.05).Hypoglycemia occnrredin in one patient in the observation group.There was no significant difference in BMI between the groups and before and after the treatment (P＞0.05).There was no significant difference in the incidence of hypoglycemia between the groups after the treatment (P＞0.05).Conclusion: The combination of sitagliptin and irbesartan in the treatment of early diabetic nephropathy can effectively decrease blood glucose, reduce mAlb excretion and delay the progression of nephropathy.

Objective To study the anti-depressive mechanisms of acupuncture by investigating the effects of acupuncture on depressive behaviors and amino-neurotransmitter in hippocampus in rats treated with chronic mild unpredicted stresses.Methods Thirty adult SD rats were randomly divided into a normal group,a depressive model group and an acupuncture group,with 10 rats in each group.Separated feeding,long-term unpredictable and middle stimulation stress were used for development of depression rat model.At the same time,the third group was treated by acupuncture.Autonomic behavior was measured with Open Field test and concentration of amino-neurotransmitter in hippocampus was measured by high performance liquid chromatography coupled with fluorescence detection.Results Compared with the normal group,autonomic activity of the rats and the concentration of GABA were significantly reduced in the model group,while the concentration of Glu was significantly increased(P0.05).Conclusion Acupuncture could reverse the depressive behaviors of rats caused by middle stimulation stress,and its anti-depressive mechanisms is related to the function of regulating the concentration of amino-neurotransmitter in hippocampus.

A method was developed for purification of 20S proteasome (20S core particle, CP) by combining differential centrifugations with nondenaturing polyacrylamide gel electrophoresis (native-PAGE), irrespective of species origins of CPs. CP purified from human erythrocytes was subjected to proteomic analysis by two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), revealing 33 spots of subunit isoforms with different molecular weights and isoelectric points, more than 14 constituent subunits. Furthermore, other four CPs were purified from yeast, mouse liver, two pancreatic cancer cell lines SW1990 and PANC-1 using this method mentioned above, and subjected to proteasome heterogeneity analysis by native/SDS-PAGE (native/sodium dodecyl sulphate polyacrylamide gel electrophoresis), together with CP from erythrocytes. The method described acts as a rapid and effective tool for CP isolations, and the results obtained may be served as a footstone for the investigations of species-dependent proteasome heterogeneity.

Meisoindigo is an indigo natural derivative commonly used in anti-cancer therapy. In the clinical application, it was also found to have good therapeutic effect on psoriasis. In order to further understand its mechanism of action, human normal keratinocyte cell line HaCaT and RAW 264.7 were used to identify if meisoindigo could affect the inflammatory factors such as NO and other important cytokines which were highly involved in psoriasis. Our results indicated that meisoindigo decreased the production of NO in LPS-stimulated RAW 264.7 cells and reduced the expression of cytokines in LPS-stimulated HaCaT cells. And TLR4-TAK-NF-kappaB was a possible pathway mainly involved in the attenuation of iNOS and pro-inflammatory cytokine production by meisoindigo, which may take part in the therapeutic effect of meisoindigo on psoriasis.

Objective To investigate the value of magnetic resonance imaging (MRI)-based intravenous thrombolysis in patients with wake-up ischemic strokes (WUIS).Methods Patients presenting within 12 hours of acute stroke symptom onset and those with WUIS confirmed by CT,excluding intracranial hemorrhage,were encouraged to perform an emergent brain MRI scan to confirm the diagnosis of hyperacute ischemic stroke (hyper-intense in DWI without hyper-intense change in T2WI or fluid attenuated inversion recovery (FLAIR)).These patients then received intravenous thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA).All patients were divided into either stroke presenting within 12 hours or WUIS.The clinical outcomes were assessed by the modified Rankin scale (mRS) and the Barthal index (BI) at baseline and at 90 days after the thrombolysis therapy.Results Two hundred and sixty-one patients (261/563,56.4％) had confirmed diagnosis of hyperacute ischemic stroke (WUIS,n =73,73/121 =60.3％ vs within 12 hours,n =188,188/342 =55.0％).Altogether,192 patients (139 in within 12 hours group,and 53 in WUIS group) received intravenous thrombolytic therapy with rt-PA.No significant differences were found between the 2 groups at the baseline characteristics and at 90 days outcomes after the thrombolysis therapy(x2 =1.296 and 1.473,P =0.538 and 0.489,respectively).Also no significant differences were found in the incidence rate of secondary hemorrhage (including both of asymptomatic and symptomatic) and mortality rate between the 2 groups.Conclusion MRI-based intravenous thrombolysis is safe and effective in the treatment of patients with hyperacute WUIS.

Enterovirus 71 (EV71) is a common cause of Hand, foot, and mouth disease (HFMD) and may also cause severe neurological diseases, such as encephalitis and poliomyelitis-like paralysis. To examine the genetic diversity of EV71, we determined and analyzed the complete VP1 sequences (891 nucleotides) from nine EV71 strains isolated in Fuyang, China. We found that nine EV71 strains isolated were over 98% homologous at the nucleotide level and 93%-100% homologous to members of the C4 subgenogroup. At the amino acid level, these Fuyang strains were 99% -100% homologous to one another, 97%-100% homologous to members of the C4 subgenogroup, and the histidine(H) at amino acid position 22 was conserved among the Fuyang strains. The results indicate that Fuyang isolates belong to genotype C4, and an H at position 22 appears to be a marker for the Fuyang strains.

Objective · To investigate the status of depression and anxiety in patients with recurrent spontaneous abortion (RSA) and the possible influence factors and to provide theoretical support for further psychological intervention. Methods · RSA patients and women with no history of RSA were invited to complete a questionnaire, including basic information, Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS). All data were analyzed by SPSS. Results · Of all 1064 cases included in this study, 725 were RSA cases, 217 cases with one spontaneous abortion and 122 in control group with no history of spontaneous abortion. Our results showed that both RSA patients and patients with one spontaneous abortion have significantly higher SDS and SAS scores than control group. Furthermore, non-pregnant RSA patients with lower education level, lower household income and 3-5 years of marriage have significantly higher levels of depression and anxiety. Patients with multiple miscarriages (≥4), history of induced abortion and no live birth, score significantly higher in SDS. Conclusion · Whether pregnant or not, RSA patients are much easier to become depressive and anxious, which may be associated with education level, household income, length of marriage, numbers of pregnancy losses and previous live birth. Women with one spontaneous abortion also show a significant higher tendency of depression and anxiety. These patients should be given proper psychological intervention if necessary.

Gallstone ileus is a rare and potentially serious complication of cholelithiasis.Its clinical symptoms are nonspecific.From March 2005 to September 2012,19 patients with gallstone ileus confirmed by surgery or endoscopy were admitted to the Pudong New Area People's Hospital.The accuracies of X-ray,uhrasonography,CT and magnetic resonance imaging (MRI) were 0/10,0/5,19/19 and 9/9,respectively.CT examination might be the first choice for diagnosing gallstone ileus ; the classical computed tomography (CT) presentation of gallstone ileus was the Rigler triad,including pneumobilia,ectopic stone and mechanical ileus; MRI examination was superior to CT examination in exposing the fistula,and can provide abundant information,which is important for designing the surgical procedures and judging the prognosis; X-ray and ultrasonography are beneficial in screening the diseases.

The recombinant adenovirus Toll like receptor 4 (TLR4) shRNA vector (pGSadeno-TLR4) was constructed and transfected into human aortic vascular smooth muscle cells (HA-VSMC).After HA-VSMC were treated with palmitate or different signaling pathway inhibitors,the mRNA and protein levels of interleukin-6 (IL-6)and NF-κB activity were tested with real-time PCR and ELISA,respectively.The results showed that palmitate increased mRNA and protein levels of IL-6 in HA-VSMC in a dose-dependent manner.The expression of IL-6 mRNA reached peak after treatment with 400 μmol/L of palmitate for 6 h,being 10.43 fold of control (P＜0.01).Treatment with 400 pmol/L of palmitate for 24 h maximally upregulated the protein level of IL-6,which was 2.18 fold of control (P＜0.01).NF-κB inhibitor parthenolide markedly inhibited palmitate-stimulated increased in IL-6 mRNA level by 65％ and protein level by 59％ (both P＜0.01).Protein kinase C (PKC) inhibitor chlerythrine suppressed palmitateinduced IL-6 mRNA expression by 24％ and IL-6 protein level by 28％.By contrast,extracellular signal-regulated protein kinase inhibitor PD98059 and phosphatidylinositol 3-kinase inhibitor wortmannin had no effect on the induction of IL-6 by palmitate.Blockade of TLR4 with pGSadeno-TLR4 significantly suppressed palmitate-induced IL-6 mRNA expression by 72％ and IL-6 protein expression by 75％ (both P＜0.01),along with decrease of NF-κB p65 activity decreased by 62％.These results suggest that TLR4/NF-κB and PKC pathways mediate palmitate-induced IL-6 expression in HA-VSMC.