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.

Objective To explore the effects of aqueous extracts of Codonopsis Radix onD-galactose induced aging model mice; To discuss the anti-aging molecular mechanism of Codonopsis Radix.Methods Subcutaneous injection ofD-galactose solution was used to establish aging models. 100 Kunming mice were divided into normal control group, model group and low-, medium-, high-dose of Codonopsis Radix interventional groups randomly, 20 mice in each group. Low-, medium-, high-dose of Codonopsis Radix interventional groups were given relevant dosage for gavage, while normal control group and model group were given the same volume of NS by gavage for 42 d. After treatment for 42 days, the BUN and CREA in mouse serum were examined; the AffymetrixmiRNA 4.0 microarray was employed to identify the differentially expressed microRNA (miRNA) related with these processes; the bioinformatic tools were also used to further analyze the cluster of miRNA microarrys and the pathways which the target genes of miRNA were involved in.Results Compared with normal control group, the levels of BUN and CREA in mouse serum increased in model group (P<0.05); compared with model group, the levels of BUN and CREA in Low-, medium-, high-dose of Codonopsis Radix interventional groups decreased, in which high-dose of Codonopsis Radix could most significantly inhibit the level of BUN (P<0.05); the cluster analysis showed the miRNA expression profilings of high dose of Codonopsis Radix interventional group and normal control group were brought together, while the profiling of model group was clearly divided with the other groups. In model group vers normal control group, 36 differentiated expressed miRNA showed, which predicated in 10 main biological functions. In high-dose of Codonopsis Radix interventional group vers model group, 34 differentiated expressed miRNAs in high-dose of Codonopsis Radix interventional group showed, and the analytical results of biological functions of target genes were the same as those of model group vers normal control group.Conclusion In the anti-aging process, Codonopsis Radix can not only influence the miRNA expression profiling, but also influence its functional environment.

Protein tyrosine phosphatase (PTP) 1B is a potential target for the treatment of diabetes and obesity. Phosphotyrosine (pTyr) is the substrate for PTP1B dephosphorylation. Malonic acid moiety was used herein as a mimic of the phosphate group in pTyr, and novel malonic acid derivatives 1-7 were designed, synthesized and evaluated as PTP1B inhibitors. Results from enzymatic assays indicated that compounds 3 and 4 exhibited potent inhibition against human recombinant PTP1B with IC50 values of 7.66 and 1.88 micromol x L(-1), respectively.

Objective To explore contrast-enhanced ultrasonography (CEUS) in diagnosis renal injuries complicated with active bleeding of different velocity,and analysis the related factors of renal traumatic degree.Methods Thirty-four Ⅰ - Ⅴ grade lesions of renal injury were made in 4 dogs and 6 New Zealand rabbits.Two and three dimensional CEUS were used to observe traumatic extension,and traumatic position,involving in vascular as well.Then the injury condition was classified and assessed synthetically.Results The range of lesions observed by using 2D and 3D ultrasound had consistency with those of the pathologic sample (length-diameter:F =0.4724,P =0.6252; transverse diameter:F =1.6174,P =0.20490),3D-CEUS can display the vascular that involved by renal injury.In the same traumatic extension condition,the time of animal becoming shocked and injury severity was related to not only traumatic extension but also different velocity of active bleeding and involving in vascular.Conclusions Contrastenhanced ultrasound can objectively reflect renal injury severity,and more information can be provided to clinical for management.

Objective To quickly evaluate the traumatic degree of abdominal solid-organs using contrast-enhanced ultrasonography (CEUS) and analysis on related factors with clinical treatment.Methods 52 patients with abdominal traumatic were observed by CEUS,and the traumatic degree was judged according to American Association for the Surgery of Trauma (AAST).The change of peritoneal fluid was observed with ultrasonography,and active bleeding and involve adjacent vessels their branches were observed with CEUS.In this way,a method of quickly evaluate the traumatic degree was established,and the correlation between indifferent grade trauma and appropriate interventions that include surgical and conservative treatment was studied.Results 52 patients with 71 lesions,compound injuries accounted for 82.7％ (43/52).Among them,37 lesions were Ⅰ-Ⅲ grade trauma,34 lesions were severe trauma of Ⅳ-Ⅴ grade.The lesions complicated with active bleeding were 76.1％ (54/71).The amount of peritoneal fluid was increased significantly within 30 min (P ＜0.05) in traumatic lesions with rapid bleeding.Among of 50lesions associated with active bleeding,the surgical treatment was 24.0％ (12/50),the conservative treatment was 76.0％ (38/50).Among of trauma lesions involving the two following vessels,Ⅰ-Ⅲ grade was 97.3％ (36/37),Ⅳ-Ⅴ grade was 61.8％ (21/34).Trauma involvement above level 2 focal blood vessels,surgical treatment accounted for 23.1％ (12/52),conservative treatment accounted for 44.2％(23/52).Conclusions The severity of the trauma can not be a comprehensive response by AAST,becauce it is not only related to the scope of the traumatic lesions,vascular level,also involved with the trauma associated with active bleeding,bleeding speed and amount of peritoneal effusion and other factors.

Objective The purpose of this study was to investigate the differences of cognitive impairment and neuropsychiatric behavior disturbances between Alzheimer's disease (AD) and frontotemporal dementia (FTD) patients,as well as their relationships with dementia severity.Methods A total of 38 FTD patients and 46 AD patients were recruited in this study.The Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) were used to evaluate the degree of cognitive impairments.The Neuropsychiatric Inventory Brief Questionnaire Form (NPI) and Frontal Behavioral Inventory (FBI) were used to measure behavioral disturbances.The 21-items Hamilton Depression Rating Scale (HAMD-21) was used to evaluate the mental or emotional state of patients.Clinical dementia rating scale (CDR) was used to divide the dementia severity.Results FTD patients were younger ((70.13 ± 8.36) years vs (66.46 ± 7.04) years,t =2.124,P =0.037),earlier at age of onset ((68.58 ± 8.51) years vs (64.43 ± 6.82) years,t =2.396,P =0.019),with lower MoCA scores (12.50 (8.00,16.25) vs 17.00(10.75,21.00),Z=-2.428,P=0.015),higher NPI (15.00(7.00,25.50)vs 9.50(4.00,17.75),Z=-2.251,P=0.024),FBI (21.00(13.00,27.00)vs 16.00(10.75,23.00),Z=-2.159,P=0.031),FBI-A (13.00 (8.00,16.00)vs 9.00(6.00,12.00) Z=-2.159,P=0.041),FBI-B (9.00(7.00,14.00) vs 7.00(3.00,11.00),Z=-2.051,P=0.040) and HAMD-21 scores (7.00(2.75,14.00) vs 5.00 (3.00,8.00),Z =-2.061,P =0.039).A detail analysis of different cognitive domains showed the executive functions (Z =-2.140,P =0.032),language (Z =-3.357,P =0.001),abstraction (Z =-2.498,P =0.012) and delayed recall (Z =-4.317,P =0.000) of the MoCA scale were lower in FTD patients than that in AD patients,while AD patients had lower scores in memory (Z =-1.999,P =0.046) and orientation (Z =-2.941,P =0.003) of the MMSE scale.Within the subscale scores of the NPI,the agitation (Z =-3.255,P =0.001),disinhibition (Z =-3.093,P =0.002) and irritability (Z =-2.214,P =0.027) scores were higher in FTD patients than in AD patients.The total scores of NPI (r=0.279,P=0.010),FBI (r =0.353,P=0.001),FBI-A (r=0.386,P=0.000) and FBI-B (r =0.273,P =0.012) were positively correlated with the CDR scores,whereas MoCA scores were negatively correlated with the CDR scores (r =-0.760,P =0.000).The subscale scores on MoCA and NPI areas changed corresponding with dementia severity in both groups.Conclusions The cognitive function,behavioral and psychological symptoms between FTD and AD patients are different.FTD patients have poorer executive function,language,abstraction and delayed recall ability,whereas AD patients perform worse in memory and orientation.With the progression of the disease,FTD patients gradually emerged disorientation,while the cognitive impairment in AD patients almost affected all the areas.FTD patients are more likely to have agitation,disinhibition and irritability behavior,and AD patients are more likely to have depression in the late stage.Dynamic evaluation of the cognitive function,behavioral and psychological symptoms in clinical practice can help to distinguish FTD and AD.

Objective:To analyze the chemical constituents in Radix astragali by high-performance-liquid chromatography-time of flight mass spectrometry(HPLC-TOF/MS). Methods:An Agilent poroshell 120 SB-C18 column(100 mm × 3 mm,2. 7 μm)was adopt-ed. The mobile phase was composed of acetonitrile-0. 1% formic acid with nonlinear gradient elution. The flow rate was 0. 4 ml· min-1 . The UV detection wavelength was set at 254nm, the column temperature was 25℃ and the injection volume was 10μl. Electron spray ionization and positive mode was adopted, the flow and temperature of the carrier gas( N2 ) was 10 L·min-1 and 350℃, respec-tively. The capillary voltage was 4 kV, the bombardment voltage was 165 V, the spectra were recorded within the range of m/z 100~1 100. Results:A total of 24 chemical constituents were identified from Radix astragali by HPLC-TOF/MS simultaneously. Conclu-sion:An efficient and fast HPLC-TOF/MS approach has been established for studying the chemical constituents in Radix astragali, which lays the foundation for the study on pharmacodynamic material basis and quality control of Radix astragali.

Objective To explore the clinical application value and feasibility of contrast-enhanced ultrasonography (CEUS) in rapid diagnosis for bleeding of hepatocellular carcinoma. Methods From January 2009 to December 2012, 58 patients from the 302nd Hospital of the People′s Liberation Army underwent CEUS and conventional ultrasound, who were suspicioused primary bleeding of liver cancer or secondary bleeding of liver cancer after percutaneous radiofrequency ablation (RFA). The change of effusion volume in front of liver and in abdominal cavity, the perfusion time, range and characteristics of contrast agent, tumor vessel and the characteristic manifestation of active bleeding within the tumor and subcapsular were evaluated. Theχ2 test was used to compare the show rates of lesion boundary and the bleeding point by conventional ultrasound and CEUS. The t test was used to compare the change of effusion in front of liver and in abdominal cavity from 0 min to 30 min after bleeding were diagnosis by CEUS. Results For 58 cases of suspicious rupture and bleeding of liver cancer, 34 cases were conifrmed by clinical and imaging ifndings. The bleeding points were detected by conventional ultrasound in 5 cases. The bleeding points in 30 cases (including 4 cases of rapid bleeding, 7 cases of medium bleeding and 19 cases of slow bleeding) were detected by CEUS. The detection rate of lesion boundary, tumor vessel and bleeding point of CEUS were higher than those of conventional ultrasound, and the differences were statistically significant (χ2=10.350, P=0.001; χ2=4.300, P=0.034;χ2=36.790, P=0.0007). CEUS showed that contrast agent continuously concentrated at the bleeding point of lesions, and different degrees of bleeding were shown as′jet-like′,′linear′or′intermittent′spillover. The volume of effusion in front of the liver and in abdominal cavity at 30 min was more than those at 0 min after bleeding were diagnosis by CEUS, and the differences were statistically significant (the volume of effusion in abdominal cavity:t=-3.467, P=0.026;t=-12.895, P=0.000;t=-3.055, P=0.007;the volume of effusion in front of the liver:t=-8.110, P=0.001;t=-5.642, P=0.002;t=-5.981, P=0.000). Conclusions CEUS can show direct signs of rupture and bleeding of liver cancer, and the degree of bleeding can be evaluated according to the extravasation characteristics of contrast medium and the changes of lfuid volume. Therefore, CEUS can provid an objective basis for rapid diagnosis of ruptured hepatocellular carcinoma in the emergency scene and bedside.

Guillain-Barré syndrome (GBS) defines a kind of Immune-mediated acute inflammatory peripheral neuropathy. Miller-Fisher Syndrome (MFS) is a special variant of GBS, with mostly one-way course and rare clinical recurrence. Only a few recurrent cases have been reported in China. Here we report a case of a young male patient with double vision and progressive aggravation of limb numbness, acute onset, with symptoms of upper respiratory tract infection before onset, accompanied by pupil abnormalities and autonomic nervous dysfunction, who was was admitted to our hospital for similar symptoms 3 years ago and was improved by immunotherapy. The patient had a triad of “ataxia, areflexia and ophthalmoplegia”. Cerebrospinal fluid showed protein-cell separation. Serum anti-Sulfatides antibody IgM, anti-GT1a antibody IgG, anti-GQ1b antibody IgG and anti-GM3 IgM were positive. Recurrent MFS was diagnosed and the symptoms improved after immunotherapy. This case suggests that MFS is clinically heterogeneous, a few patients can present with relapse and generally have a better prognosis with immunotherapy. Pre-existing infection and anti-GQ1b antibody production may be predisposing factors for MFS recurrence.

Objective To explore the diagnostic value of Alzheimer-associated neuronal thread protein(AD7C-NTP)and olfactory function in the differentiation of three types of dementia,and to evaluate their clinical application value.Methods Mini-Mental State Examination (MMSE)and Montreal Cognitive Assessment(MoCA)were applied to evaluate cognitive function of all subjects with Alzheimer disease(AD),frontotemporal dementia (FTLD),or mixed dementia (MD).Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression levels of AD7c-NTP in urine.T&T test method was applied to detect the olfactory function.Spearman rank correlation was used to evaluate the correlation of urine AD7c NTP with MMSE and MoCA scores.Results There was no significant difference in the demographic profile (except age)among three types of dementia of AD,FTLD and MD(F =4.05,P =0.02).Among the three dementia groups,the mean age of the MD group was highest.The statistically significant difference in MMSE scores was found among the three groups(F 3.79,P=0.03),while there was no significant difference inMoCAand NPI scores among the three dementia groups.The levels of the urine AD7c-NTP were different among the three dementia groups,but without statistical significance(H 1.25,P =0.53).Additionally,the FTLD group had the highest urine AD7c NTP level.Spearman rank correlation analysis showed no correlation of AD7c-NTP with MMSE and MoCA(r =0.18,P =0.25;r =0.14,P =0.39,respectively).No differences in olfactory function of the recognition domain(H =3.40,P=0.18)and in the detection domain(H =2.07,P=0.36)were found among three dementia groups of AD,FTLD and MD.Conclusions The level of urine AD7c-NTP is not of clinical significance in differentiating three types of dementia,and it is not correlated with the MMSE and MoCA scores.This study fails to find the clinical value of olfactory function test for distinguishing three types of dementia.