0.05 compared with group B);ZT and Youjiangtang Tablets had similar effect in promoting the synthesis of hepatic glucose and the release of serum insulin(P

Though all the marketed drugs of dipeptidyl peptidase IV inhibitors are structurally different, their inherent correlation is worthy of further investigation. Herein we rapidly discovered a novel DPP-IV inhibitor 8g (IC50 = 4.9 nmol.L-1) which exhibits as good activity and selectivity as the market drugs through scaffold hopping and drug splicing strategies based on alogliptin and linagliptin. This study demonstrated that the employment of classic medicinal chemistry strategy to the marketed drugs with specific target is an efficient approach to discover novel bioactive molecules.

Objective To investigate the biodistribution and gamma imaging of 99Tcm-arginine-glutamate-threonine (RET) in nude mice bearing lung cancer xenografts and to explore its feasibility for human lung cancer imaging.Methods RET was labeled directly with 99Tcm.The binding efficiency of 99Tcm-RET with human NSCLC H1299 cells was measured.99Tcm-RET was injected via the tail vein in nude mice bearing H1299 xenografts.The mice(n=32) were sacrificed at different time points:15 min,30 min,1 h,2 h,4 h,8 h,24 h,and 48 h.Organs of interest were excised,weighted and counted by a gamma counter.The organ uptake was calculated as ％ID/g.The gamma imaging was performed on 3 mice at 0.5,1,2,4,4.5,5,6 h after intravenous injection of 4.81 MBq 99Tcm-RET.Results The radiolabeling yield of 99Tcm-RET was (93.15±2.02)％,and the binding efficiency of 99Tcm-RET with H1299 cells was (3.56±0.37)％.At 4 h after injection,the uptake of tumor,liver and spleen was (4.96±1.05) ％ID/g,(15.89±1.84) ％ID/g and (10.83±1.66) ％ID/g and the T/NT was 5.70±0.21 for the heart and 12.40±0.11 for the blood.The tumor in nude mice could be best visualized at 4.5-6.0 h.Conclusion 99Tcm-RET might have potential to serve as a lung cancer imaging agent.

Serum levels of CXC chemokine ligand 10 (CXCL10) and chemokine receptor 3 (CXCR3) were determined in 50 patients with type 1 diabetes mellitus (T1 DM) and 30 normal control subjects by ELISA method.The results showed that serum levels of CXCL10 and CXCR3 in T1DM patients were significantly higher than those in normal subjects [(258.17 ± 39.12 vs 96.47 ± 26.91) ng/L,(851.87 ± 70.04 vs 441.82 ± 72.24) pg/ml,both P＜0.05].Serum level of CXCL10 in patients dropped sequentially with durations of diabetes ＜6 weeks,≥6 weeks or ＜3 years,and ≥ 3 years,being statistically significant between groups (P＜0.05).These results suggest that serum levels of CXC10 and CXCR3 may reflect the immune activity in T1DM.

Objective To examine the association of arteriovenous fistula (AVF) blood flow (Qa) dynamics with inflammation state and its effect on cardiovascular diseases (CVD) in maintenance hemodialysis (MHD) patients.Methods Thirty MHD patients with AVF and twelve healthy people were enrolled in the study.Qa and cardiac output (CO) were measured by Transonic Hemodialysis Monitor HD 02.In MHD patients,pre-dialysis blood samples were taken before Qa monitoring.High-sensitivity C-reactive protein (hsCRP) was measured by immunoturbidimetry (Kyoma,Japan).Inflammatory factors IL-2,IL-6,IL-10,TNF were measured by Cytometric Bead Array (BDTM).Cardiovascular diseases morbidity was monitored prospectively within nineteen months follow-up period.Results There were no significant differences in age and sex between MHD patients and healthy people.The serum IL-6,IL-10,TNF and hsCRP were significantly higher in MHD patients than those in healthy controls [2.38 (1.86-4.69) vs 1.14 (0.27-1.18) ng/L,P＜0.01; 1.47 (1.19-2.10) vs 1.04 (0.00-1.23) ng/L,P＜0.01; 1.33 (1.05-1.56) vs 0.54 (0.00-1.24) ng/L,P＜0.05; 4.90 (1.58-7.45) vs 1.50 (0.63-1.90) mg/L,P=0.01].During the follow-up period,6 patients (20.0％) developed at least one episode of cardiovascular event.Qa,serum IL-6 and hsCRP levels were significantly higher in patients with CVD as compared to those without CVD [(1120±192) vs (893±189) ml/min,P＜0.05; 4.86 (2.96-7.85) vs 2.20 (1.80-3.10) ng/L,P＜ 0.01;11.75 (3.83-31.53) vs 4.45 (1.05-6.68) mg/L,P＜0.05].Binary Logistic regression analysis demonstrated that serum IL-6 was an independent and stronger risk factor for CVD morbidity [HR=1.943,95％CI (1.110-3.402),P=0.02].Spearman rank correlation analysis and liner regression analysis showed that Qa was positively correlated with serum IL-6 (β=0.492,P＜0.01).Path analysis suggested that Qa contributed to CVD mortality via the increase of serum IL-6.Conclusions AVF blood flow monitoring is important for MHD patients.IL-6 is an independent risk factor of CVD in MHD patients.AVF blood flow increases cardiovascular diseases morbidity in MHD patients via its promotion of IL-6 production.

Objective To analyze the changes in peripheral blood monocyte subpopulations in patients with primary, secondary and latent syphilis. Methods Flow cytometry was used to detect CD14highCD16- and CD14+CD16+ monocyte subpopulations in peripheral blood from 58 patients with untreated syphilis, including 36 cases of latent syphilis,8 cases of primary syphilis and 14 cases of secondary syphilis, as well as from 65 normal human controls. Restflts Compared with the normal controls, the proportion of CD14+CD16+ monocytes among total monocytes was significantly elevated (12.0% ± 5.0% vs 6.0% ± 3.3%, t = 7.25, P < 0.01), while that of CD14highCD16- monocytes was down-regulated (88.0% ± 5.1% vs 94.0% ± 3.5%, t = -7.20, P < 0.01). No statistical difference was observed in the proportion of CD14+CD16+ or CD14hhighCD16- monocytes among the patients with primary syphilis, secondary syphilis and those with latent syphilis (all P > 0.05). Conclusions The changes in peripheral blood monocyte subpopulation in patients with untreated syphilis may be associated with the permanent infection of Treponema pallidum, but have no obvious correlation with clinical stage of syphilis.

Acute lymphoblastic leukemia (ALL) with intra-chromosomal amplification of chromosome 21(iAMP21) accounts for approximately 2% of children′s B-cell precursor ALL(BCP-ALL). iAMP21 is a complex genetic abnormality that is highly heterogeneous among patients.The mechanism of iAMP21 may be related to breakage-fusion-bridge (BFB) cycle, rob(15; 21)c and r(21)c.Patients with iAMP21-ALL are older and asso-ciated with lower white blood cell and platelet counts and poor prognosis and increasing the intensity of chemotherapy can improve the prognosis of patients.The advances of genetic abnormalities, formation mechanisms, clinical features, prognosis and treatment of iAMP21-ALL was reviewed in this article.

Objective To observe the influencing of Yiqi Huayu Jiedu Prescription on the growth of HepG2 nude mice transplantation tumor and the expression of related factors of vascular mimicry. Methods Models of transplanted tumors, which were made by HepG2 cells in nude mice, were randomly divided into 7 groups, Yiqi Huayu Jiedu Prescription group, Astragali Radix group, Curcumae Rhizoma group, Paridis Rhizoma group, Gecko group, cis-platinum group, and model group. Except for the model group, the rest groups were given relevant medicine for intervention. 21 days later. HIF-1α, MMP-2, MMP-9, and E-cad were detected by immunohistochemistry, and Twist1 and Bcl-2 were detected by fluorescence quantitative PCR. Results Compared with the model group, tumor volume in the rest groups decreased (P<0.05), and the effect in the Yiqi Huayu Jiedu Prescription group was more obvious than the Astragali Radix group, Paridis Rhizoma group and Gecko group (P<0.05);The expression of vasculogenic mimicry structure was rare in each group, and the model group and cis-platinum group were the most obvious;Except for the Astragali Radix group, the expressions of HIF-1α, MMP-2, and MMP-9 showed statistical significance compared with model group (P<0.05);The expression of E-cad in the Yiqi Huayu Jiedu Prescription group and Astragali Radix group showed statistical significance (P<0.05);The expression of Bcl-2 in the Yiqi Huayu Jiedu prescription group, Paridis Rhizoma group, and Gecko group decreased significantly compared with the model group (P<0.05);The expression of Bcl-2 in the Yiqi Huayu Jiedu prescription group was much better than the other groups (P<0.05);The expression of Twist1 showed statistical significance in the Yiqi Huayu Jiedu Prescription group, Curcumae Rhizoma group, Paridis Rhizoma group, and cis-platinum group (P<0.05). Conclusion Yiqi Huayu Jiedu Prescription can reduce expression of HIF-1α, Twist1, Bcl-2, MMP-2, and MMP-9, and increase expression of E-cad, thereby inhibiting the formation of vascular mimicry.

OBJECTIVE:To study the preventive effect and mechanism of Wei medicine Kunlun snow chrysanthemum polysac-charides(KSCP)on carbon tetrachloride(CCl4)-induced acute liver injury in mice. METHODS:96 mice were randomly divided in-to normal group(normal saline),model group(normal saline),Biphenyl diester dropping pill(positive control,1.5 mg/10 g)and KSCP low-dose,medium-dose,high-dose groups (0.3,0.6,1.2 mg/10 g),16 in each group,with intragastric administration, once a day,for 10 d. Except for normal group,mice in other groups were intraperitoneally injected 1%CCl4 rapeseed oil solution to induce liver injury. After 24 h of modeling,the levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),tu-mor necrosis factor α(TNF-α),interleukin 1(IL-1)in serum,levels of malondialdehyde(MDA),superoxide dismutase(SOD) in liver tissue were detected;the liver,spleen indexes were calculated. Pathological changes of liver tissue were observed,patho-logical scoring was conducted. The protein expressions of apoptosis-related genes Caspase-3,Bcl-2,Bax in liver tissue were detect-ed. RESULTS:Compared with normal group,levels of ALT,AST,TNF-α,IL-1 in serum,MDA level in liver tissue and liver, spleen indexes in model group were obviously increased(P<0.01);SOD level in liver tissue was decreased(P<0.01);pathologi-cal changes in hepatocellular necrosis,degeneration and inflammatory cell infiltration,and pathological score in model group was obviously increased(P<0.01);caspase-3 protein expression and Bcl-2/Bax ratio in liver tissue in model group were obviously de-creased (P<0.01). Compared with model group,above-mentioned indexes in each administration group were obviously improved (P<0.05 or P<0.01). CONCLUSIONS:KSCP has certain preventive effect on CCl4-induced acute liver injury in mice,and its mechanism may be associated with anti-oxidation,anti-inflammation and regulation of apoptosis-related protein expressions.

Objective To evaluate the consistence in the detection of antibodies against HIV-1 between a new rapid test using oral mucosal transudate (OMT) samples and ELISA using serum samples. Methods Two-hundred patients who were positive for anti-HIV-1 antibodies by serum ELISA and confirmed by Western blot to be infected with HIV, and 600 healthy human controls negative for anti-HIV-1 antibodies by serum ELISA, were eligible for this study. OMT samples were collected from these subjects and subjected to a rapid test for anti-HIV-1 antibodies. The factors influencing the performance of the rapid test were analyzed. Results Of the 200 OMT specimens from HIV-infected patients, 198 showed positive reaction, 2 showed negative reaction. Among the 198 positive reactions, 192 (96%) were "clear" and easy to make decisions, 4 (2%) were "faint", 2(1%) were "very faint" and required professionals to make decisions. The rapid test was negative in all the 600 OMT specimens from the control group. Conclusions The consistence in the detection of anti-HIV-1 antibodies between the OMT rapid test and serum ELISA was 99% in HIV-positive specimens, 100% in HIV-negative specimens, and 99.75% in all the specimens.