Protein tyrosine phosphatase (PTP) 1B is a potential target for the treatment of diabetes and obesity. We have previously identified the benzoyl sulfathiazole derivative II as a non-competitive PTP1B inhibitor with in vivo insulin sensitizing effects. Preliminary SAR study on this compound series has been carried out herein, and thirteen new compounds have been designed and synthesized. Among them, compound 10 exhibited potent inhibition against human recombinant PTP1B with the IC50 value of 3.97 micromol x L(-1), and is comparable to that of compound II.
Humans ; Protein Tyrosine Phosphatase, Non-Receptor Type 1 ; antagonists & inhibitors ; Structure-Activity Relationship ; Sulfathiazoles ; chemistry ; pharmacology

ObjectiveTo investigate the effects of heme oxygenase- 1 ( HO- 1 ) on pancreas and liver in severe acute pancreatitis(SAP) rats, and explore its probable mechanism. MethodsA total of 40 male SD rats were randomLy divided into 4 groups: control group(n = 10) ; SAP group(n = 10) ; HO-1 stimulation group (75 μg/kg hemin was injected intraperitoneally at 30 minutes after model establishment, n = 10 ) ; HO-1 inhibition group(20 μg/kg ZnPP was injected intraperitoneally at 30 minutes after model establishment, n = 10). Sodium Cholate (3％) was retrogradedly injected into the pancreatic duct to produce the SAP model. To observe the histopathological changes of pancreas, liver tissues were observed and serum, pancrease and liver tissues concentration of HO-1, IL-10 and TNF-α in different groups were observed 24 h after the SAP model establishment. ResultsCompared with those in SAP model group, the pathological scores were lower in HO-1 stimuLation group[ (7.50 ±0.58) vs (10.50 ±0. 71) ; ( 1.20 ±0.42) vs (1.70 ±0.48) ]( P ＜ 0.05 ), and the serum, pancreas and liver tissues HO- 1 [ (0.97 ± 0.02) ng/mL, (0.78 ± 0.09) ng/mL,(0.73 ±0.05) ng/mL]and IL-10[(101.72 ±2.63) ng/mL, (63.58 +1.02) pg/mL, (169.40 ±3.06) pg/mL ]concentrations were significantly elevated in HO- 1 stimuLation group ( P ＜ 0.05 ), while the serum, pancreas and liver tissues TNF-α [ (22.85 ± 1.74) pg/mL, (26.50 ± 1.3) pg/mL, (35.88 ±0.98 ) pg/mL]concentrations were significantly decreased in HO-1 stimuLation group (P ＜ 0.05 ). Compared with those in SAP model group, the pathological scores were higher in HO-1 inhibition group (P ＜0.05 ), and the serum, pancreas and liver tissues HO-1 and IL-10 concentrations were significantly decreased( P ＜0.05 ), while the serum, pancreas and liver tissues TNF-α concentrations were significantly elevated (P ＜ 0.05 ). CondusionThe results of the study demonstrated that HO- 1 over- expression has protective effects on the pancreas and liver in SAP. UP-regulated IL-10 expression and down-reguLated TNF-α expression might be served as a potential mechanism.

Objective To assess the levels of nucleosomes released from peripheral blood mononu-clear cells(PBMC)of patients with systemic lupus erythematosus(SLE),and their relationship with auto-antibodies as well as disease activity.Methods Levels of both nucleosomes released from PBMC and vari-ous auto-antibodies were detected by ELISA in sera from SLE patients.The disease severity was evaluated using SLEDAI(systemic lupus erythematosus disease activity index)system.Results Levels of nucleosomes released from PBMC were significantly higher in patients with active SLE than those of patients with inactive disease and normal controls(39.39?25.70,13.44?8.82,and11.73?7.87IU/mL,respectively).There was a significant positive correlation between nucleosome levels and SLEDAI scores,serum ds-DNA auto-an-tibody levels,and low C3levels.Conclusion Nucleosomes released from apoptotic PBMC of patients with SLE is closely correlated to disease activity,which implies that nucleosomes may play an important role in the pathogenesis of SLE.

Objective To investigate the role of nucleosome in the pathogenesis of systemic lupus erythematosus (SLE). Methods BALB/c mice were immunized with nucleosome, and then serum dsDNA and ANA autoantibodies were detected by ELISA. Kidney specimens were observed by immunofluorescence and histological examination. Results High titers of IgG dsDNA and ANA autoantibodies in sera of BALB/c mice were observed at the 14th day after immunization with nucleosome. Nephritis and immune complex deposition in renal glomeruli were observed at the 35th day. Conclusion Nucleosome could induce SLE-like disease in BALB/c mice, and may play a critical role in the pathogenesis of SLE.

Objective To explore impact of BMI on the clinical efficacy of treatment of type 2 diabetes mellitus after the laparoscopic gastric bypass. Methods Twenty patients were randomly selected from type 2 diabetes mellitus patients with BMI of 25 ~28 kg/m2 after laparoscopic gastric bypass surgery in our hospital from 2010 to 2013,20 patients from type 2 diabetes mellitus patients with BMI of 28~35 kg/m2 and 20 patients from type 2 diabetes mellitus patients with BMI≥35 kg/m2 . Accordingly,the total of 60 patients were divided into low BMI group,middle BMI group and high BMI group. The difference of the rate of blood glucose control and other indicators between three groups were compared and analyzed. Results The rate of blood glucose control in low BMI group was 75%,middle BMI group was 85%, and high BMI group was 90%. There was no statistical difference of the rate of blood glucose control between three groups at 12 months after laparoscopic gastric bypass surgery. The blood glucose and weight obviously improved in all patients,and fasting insulin and postprandial ser-um insulin decreased at 12 months after laparoscopic gastric bypass surgery. Conclusion All the patient of type 2 diabetes mellitus with dif-ferent BMI in three group can acquire satisfying clinical therapeutic effect after the laparoscopic gastric bypass.

OBJECTIVETo develop a mouse model of acute lung injury induced by cigarette smoke (CS) and to investigate inflammatory changes with the model.

METHODSICR mice exposed to CS for 20-min, 3/d. Bronchoalveolar lavage fluid (BALF) and lung tissue were harvested at d 0, d 1, d 3 and d 7 after CS exposure. Neutrophil count in BAFL, TNF-alpha and MMP-12 levels, the activity of MPO in lung tissue were determined.

RESULTNeutrophil count in BALF, MMP-12 and MPO levels in lung tissue were increased after CS exposure in a time-dependent manner with a peak at d3. TNF-alpha level sharply increased at d1, and remained high level until d7.

CONCLUSIONICR mice are tolerant and sensitive to CS exposure, which may be used as an appropriate animal model for acute lung injury induced by cigarette smoke.

Acute Lung Injury ; chemically induced ; pathology ; Animals ; Bronchoalveolar Lavage Fluid ; cytology ; Disease Models, Animal ; Male ; Matrix Metalloproteinase 12 ; metabolism ; Mice ; Mice, Inbred ICR ; Smoke ; adverse effects ; Tobacco ; adverse effects ; Tumor Necrosis Factor-alpha ; metabolism

Objective To evaluate the feasibility and efficacy of percutaneous nephrolithotomy (PCNL)in treating renal calculi.Methods The data of 118 patients with renal calculi who had underg- one PCNL from July 2002 to August 2004 were retrospectively analyzed.There were 86 men and 32 women. The mean age was 39 years(range,7-68 years).Of the 118 cases,11 had pelvic calculi,16 had calyx cal- culi,35 had pelvocalyceal calculi,54 had staghorn calculi,and 2 had bilateral renal calculi.The mean stone size was 2.5 cm?1.5cm(ranged from 2.0 cm?1.0 cm to 4.5cm?4.0cm).Results Of the 118 ca- ses,112 underwent one-stage PCNL,and 6,two-stage PCNL.The procedure was performed by single tract in 114 cases,and by two tracts in 4 cases.Lithotomy was done by one session in 60 cases,by 2 sessions in 42 cases,and by 3 sessions in 16 cases.The total stone clearance rate was 81.4%.The mean operative time was 120 min,and mean hospital stay was 15 d.No blood transfusion was needed during operation,and only one patient experienced bleeding(about 500 ml)after 4 d postoperatively,and was cured by conservative treat- ment such as blood transfusion and anti-inflammation.No major complications were observed in other pa- tients.Conclusions PCNL has advantages of minimal trauma,less blood loss,fewer complications,and is safe and effective in treating renal calculi,especially for patients who will have the second procedure.

BACKGROUNDThe cross-section of thoracolumbar vertebral body is kidney-shaped with depressed posterior boundary. The anterior wall of the vertebral canal is separated from the posterior wall of the vertebral body on the lateral X-ray image. This study was designed to determine the sagittal distance between the anterior border of the vertebral canal and the posterior border of the vertebral body (DBCV) and to analyze the potential role of DBCV in the estimation of cement leakage during percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP).

METHODSWe retrospectively recruited 233 patients who had osteoporotic vertebral compression fractures and were treated with PVP or PKP. Computed tomography images of T11-L2 normal vertebrae were measured to obtain DBCV. The distance from cement to the posterior wall of the vertebral body (DCPW) of thoracolumbar vertebrae was measured from C-arm images. The selected vertebrae were divided into two groups according to DCPW, with the fracture levels, fracture grades and leakage rates of the two groups compared. A relative operating characteristic (ROC) curve was applied to determine whether the DCPW difference can be used to estimate the degree of cement leakage. The data were processed by statistical software SPSS version 21.0 using independent sample t-test and Chi-square tests.

RESULTSThe maximum DBCV was 6.40 mm and the average DBCV was 3.74 ± 0.95 mm. DBCV appeared to be longer in males than in females, but the difference was not statistically significant. The average DCPW of type-B leakage vertebrae (2.59 ± 1.20 mm) was shorter than that of other vertebrae (7.83 ± 2.38 mm, P < 0.001). The leakage rate of group DCPW ≤6.40 mm was lower than that of group DCPW >6.40 mm for type-C and type-S, but much higher for type-B. ROC curve revealed that DCPW only has a predictive value for type-B leakage (area under the curve: 0.98, 95% confidence interval: 0.95-0.99, P < 0.001), and when the cut-off value was 4.05 mm, the diagnostic sensitivity and the specificity were 94.87% and 93.02%, respectively.

CONCLUSIONSDepression of the thoracolumbar posterior vertebral body may be informative for the estimation of cement location on C-arm images. To reduce type-B leakage, DCPW should be made longer than DBCV on C-arm images for safety during PVP or PKP.

Aged ; Female ; Fractures, Compression ; surgery ; Humans ; Kyphoplasty ; methods ; Male ; Middle Aged ; Osteoporotic Fractures ; surgery ; Retrospective Studies ; Spinal Fractures ; surgery ; Vertebroplasty ; methods

OBJECTIVETo explore security revaluation of Danhong injection and study correlative influencing factor of ADR/ADE.

METHODThe retrospective nested case-control study was carried out in hospitalized patients of the first affiliated hospital of Henan university of traditional Chinese medicine (TCM). The 8 452 cases of participation Danhong injection adverse reaction scentralized monitoring were defined as the study cohort. Adverse reactions occurred in patients with data as the case group, according to choose control group by methods of group design and individual matching in accordance with the ratio of 1:4 (The case group 52 cases and 208 patients in control group), to estimate the correlative fluencing factor of ADR/ADE.

RESULTThe univariate analysis indicated that factors which OR value of group design reaching significance level were gender, personal allergichistory and medication days (P<0.05), factors of individual matching OR value reaching significance level were just only medication days (P<0.05). Multivariate logistic regression analysis showed that factors screened into equation were gender and personal allergic history.

CONCLUSIONThe correlative in fluencing factor of Danhong injection adverse reactions have more correlation with taking medicine population. We should pay special attention to female and the population which have personal allergic history.

Adolescent ; Adult ; Aged ; Case-Control Studies ; Child ; Child, Preschool ; Clinical Trials as Topic ; Cohort Studies ; Drug Therapy ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Outcome Assessment (Health Care) ; Young Adult

BACKGROUNDEppin (epididymis protease inhibitor) appears to play an important role in primate fertility. However, the function of Eppin and its antibody in men and its relationship with men's infertility are poorly studied. To reveal the significance and possibility of detection of anti-Eppin antibody in clinical infertilty cases, we developed an Escherichia coli expression system for the expression of biologically active human Eppin.

METHODSThe human Eppin gene was cloned into PET-28a( )+ vector after induction with 0.5 mmol/L isopropy-beta-D-thiogalactoside (IPTG) at 26 degrees C for 4 hours, and the expressed fusion protein His6-Eppin was purified by Ni2+ affinity chromatography. Afterwards, six female 8-week-old Balb/c mice were immunized with purified His6-Eppin for three weeks. Their sera were collected and polyclonal antibodies against His6-Eppin were purified, all of which were further verified by Western-blot and immunofluorescence analysis.

RESULTSAbout 18.33 mg His6-Eppin was obtained from 1-L flask culture. The produced polyclonal antibodies against His6-Eppin recognized the Eppin protein both in human epididymis and in HEK293T cells by over-expression of the recombinant human Eppin.

CONCLUSIONThe purified His6-Eppin protein has biological activity, which might be a candidate for clinical diagnosis of infertility and development of male immuno-contraceptive agents.

Animals ; Escherichia coli ; genetics ; Female ; Fluorescent Antibody Technique ; Humans ; Mice ; Mice, Inbred BALB C ; Proteinase Inhibitory Proteins, Secretory ; immunology ; isolation & purification ; Recombinant Fusion Proteins ; immunology ; isolation & purification