DOTA and its derivatives are most widely uscd novel bifunctional chelators.They have not only mature synthesis route,but also good coordination and chelating ability.Therefore,DOTA metal complexes of DOTA-peptide conjugates are increasingly used as MRI contrast agents,radionuclide targeted imaging agents and therapeutic radiopharmaceuticals in the biomedical field.This review covers the bifunctional derivatives of DOTA,the synthesis of DOTA-peptide conjugates,and the applications of DOTA-peptide conjugate metal complexes.

AIM: To determine the role of LOX-1/PPAR pathway in regulating expression of adhesion molecules elicited by oxidizing low density lipoprotein(Ox-LDL) through Lectin-like oxidized low-density lipoprotein receptor-1(LOX-1) in human umbilical vein endothelial cells(HUVECs).METHODS: HUVECs were incubated with Ox-LDL,poly(I),carrageenan or 15-deoxy-△12,14-prostaglanding J2(15d-PGJ2).PPAR mRNA and protein were examined by real time RT-PCR and Western blotting.ICAM-1 and E-selectin were detected by RT-PCR and Western blotting respectively.RESULTS: Ox-LDL increased PPAR expression in HUVECs,which was inhibited by pretreatment of HUVECs with LOX-1 blockers.Preincubation of HUVECs with 15d-PGJ2 attenuated the expression of intercellular adhesion molecule-1(ICAM-1) and E-selectin in response to Ox-LDL.Upregulation of ICAM-1 and E-selectin mediated by Ox-LDL were suppressed more significantly by the combination of 15d-PGJ2 and polyinosonic acid as compared to either 15d-PGJ2 or polyinosonic acid alone.CONCLUSION: The results indicate that Ox-LDL exerts a biphasic effects on inflammatory response.It evokes harmful effects by inflammatory injury on one side and protective effects by triggering the LOX-1/ PPAR signaling pathway on the other hand.

Objective To observe the effects of malt extract on prolactin expression and morphology of mammary tissue in hyperprolactinemia rats. Methods Metoclopramide hydrochloride was injected subcutaneously to establish hyperprolactinemia model. Sixty rats were divided into normal control group, model control group, bromocriptine group, high-dose, middle-dose and low-dose malt extract groups. Except normal control group, hyperprolactinemia model was established in the other groups. Bromocriptine (0. 389 mg·kg-1 ·d-1 ) was given to bromocriptine group. Malt extract (7. 98, 15. 96 and 31. 92 g·kg-1 ·d-1 ) was administered in low-dose, middle-dose and high-dose malt extract groups. Equal volume of purified water was given to normal control group and model control group. After 30 days of administration, PRL positive cell number of rat hypophysis was counted. RT-PCR was used to measure hypophysis PRL mRNA expression, and morphology of mammary tissues was observed by immunohistochemical method. Results PRL positive cell number was (2. 4±0. 3), (21. 7±0. 8), (3. 8± 0. 5), (4. 5±0. 4), (6. 7±0. 5) and (15. 8±1. 2) in normal control group, model control group, bromocriptine group, high-dose, middle-dose and low-dose malt extract groups. PRL mRNA expression level was (0. 31±0. 02), (1. 58±0. 06), (0. 45± 0. 04), (0. 49±0. 03), (0. 61±0. 04), and (0. 95±0. 09), respectively. As compared with normal control group, hypophysis PRL positive cell number and PRL mRNA expression level of high-dose and middle-dose malt extract group were increased significantly (P<0. 01), and hyperplasia of mammary glands appeared. As compared with model control group, hypophysis PRL positive cell number and PRL mRNA expression level of high-dose and middle-dose malt extract group was decreased significantly (P<0. 01), and hyperplasia of mammary glands was alleviated obviously. Conclusion Malt extract can effectively treat hyperprolactinemia and inhibit hyperplasia of mammary glands through significantly decreasing the expression of hypophysis prolactin in hyperprolactinemia rats.

Objective To investigate the intervention of trans-theoretical model on the risk factors in the patients with prediabetes.Methods One hundred and twenty-two patients with pre-diabetes in a tertiary hospital of Zhengzhou City were selected and randomly assigned to control group and intervention group.The control group received the routine diabetic health education,while in addition to the routine health education,the intervention group was assisted by TTM interventional measures.The blood glucose,body mass index(BMI) and negative emotion were compared between the two groups.Results The blood glucose and BMI after intervention in the two groups were decreased,moreover the decrease level of fasting blood glucose and BMI in the intervention group was higher than that in the control group,and the difference was statistically significant(t=4.963、2.061,P＜0.05).The anxiety and depression emotion scores after intervention in the intervention group were [(3.47 ±1.07) and (0.30 ± 0.46)],before intervention were (7.74 ± 4.00) and(7.25 ± 4.50),The difference was statistically significant(P＜0.05),Moreover the anxiety and depression emotion scores after intervention in the intervention group were lower tghan those in the control group with statistical difference(t=3.300、2.054,P＜0.05).Conclusion The intervention measures based on TTM has significant advantage for controlling the risk factors of pre-diabetes and preventing diabetes than the conventional health education.

Objective To investigate the tracing value of drug-loaded nano-active carbon for lymphatic visualization and its potential application in the lymphadenectomy of gastric cancer. Methods Sixty-three patients with advanced gastric carcinoma were randomized into 2 groups:control group and tracing group. For the tracing group, 5-Fu-loaded nano-active carbon (NP-5-FU) suspension was intratumorally administered by preoperative gastroscope-guided or intra-operative injection. No tracing reagents was given in the control group. The numbers of removed lymph nodes and metastasis-involved lymph nodes as well as the lymph node staining were recorded and compared between the two groups. The adverse effects was monitored. Results The resected lymph nodes in the tracing group were much more than that of control group (43.73 ± 9. 25 vs. 25. 36 ± 4. 73, t = 3.82,P ＜ 0. 05). For the N1, N2 and N3 lymph nodes, 27. 17 ± 5. 82,13.73 ± 4. 61 and 2. 83 ± 0. 15 per case of the tracing group were desected, while they were 14. 45 ± 2. 75,8. 27 ± 1.89, and 2. 64 ± 0. 11 per case in the control group,respectively (P ＜ 0. 05 ). 26. 2% (211/842) of the lymph nodes in the tracing group showed black intensity,higher than that of unstain lymph nodes (4. 5% ,21/470,χ2 =95. 108,P ＜0. 05) and that in control group (16.9%, 142/837)( χ2 =7.485 ,P ＜ 0.05, ). No local and systemic adverse reactions were observed for the local injection of nano-active carbon. No extension of operating time and increased complications occurred. Conclusion Local injection of nano-active carbon which was loaded with 5-FU around the tumor is a very useful measure to trace the lymph nodes and facilitate the lymphedetectomy and chemotherapy.

Objective To investigate the effect of allicin on the development of atherosclerosis in apoE-/-mice and explore its underlying mechanism from the perspective of protein S-nitrosylation.Methods Thirty male apoE-/- mice were randomly divided into 3 groups:control group (saline,ig),low-dose group (allicin,9 mg/kg·d, ig)and high-dose group (allicin,18 mg/kg·d,ig).They were fed with high cholesterol diet for 12 weeks.The levels of plasma lipids,oxidized-LDL (ox-LDL),malondialdehyde,tumor necrosis factor-alpha and nitric oxide (NO)were measured.The atherosclerotic lesions in aortic root were evaluated after hematoxylin and eosin staining and elastica van Gieson and immunohistochemical staining,respectively.Furthermore,in vitro experiments were performed using human umbilical vein endothelial cells (HUVECs).The HUVECs were treated with allicin (10μmol/L or 20 μmol/L)for 24 hours in the presence of ox-LDL (50 μg/mL).The level of NO in supernatant was measured by a nitrate/nitrite assay. The protein S-nitrosylation of the HUVECs was detected through immunofluorescence.Results The histological analysis revealed that allicin treatment not only significantly decreased the areas of the atherosclerotic lesion (all P <0.05)but also suppressed the macrophage accumulation and smooth muscle cell proliferation in the lesion.There was no significant difference in the levels of plasma lipids between control and treated groups.However,allicin exerted obvious anti-oxidative and anti-inflammatory effects. Interestingly,the allicin treatment led to marked increase of the plasma NO level (P <0.05)and aortic protein S-nitrosylation.The experiments in vitro further proved that the allicin up-regulated the levels of NO and protein S-nitrosylation in HUVECs treated with ox-LDL (P < 0.01 ).Conclusion Allicin can inhibit the development of atherosclerosis.The mechanism is associated with the up-regulation of protein S-nitrosylation in endothelial cells, which plays an important role in anti-oxidization and anti-inflammation.

AIM: To explore the effect of anthocyanin on cholesterol efflux and elucidate its possible molecular mechanism. METHODS: Mouse Peritoneal macrophages were loaded with 50 mg/L AcLDL to induce macrophage-derived foam cells. Cholesterol efflux from macrophage-derived foam cells induced by anthocyanin was determined by enzymatic methods. PPAR-? mRNA and protein expression in macrophage-derived foam cells was assayed by quantitative PCR and western blotting. RESULTS: Anthocyanins had the capacity of promoting cholesterol efflux from mouse peritoneal macrophage-derived foam cells and increased PPAR-? mRNA and protein expression. CONCLUSION: Anthocyain-induced cholesterol efflux may be related to its enhancing PPAR-? mRNA and protein expression.

Objective To investigate the possible role of high mobility group box 1 protein (HMGB1) and its advanced gly‐cation end products receptor (RAGE) in the pathogenesis of systemic lupus erythematosus (SLE) .Methods The enzyme‐linked immunosorbent assay (ELISA) was used to determine the level of plasma HMGB1 in 52 cases of SLE (SLE group) and 40 healthy females undergoing physical examination (HC group) ,at the same time real time quantitative polymerase chain reaction (RT‐qPCR) was employed to detect the expression of HMGB1 and RAGE mRNA in peripheral blood mononuclear cells (PBMCs) .The correlation between plasma HMGB1 ,PBMCs HMGB1 and RAGE mRNA levels with clinical indicators was analyzed .Results The levels of plasma HMGB1 ,PBMCs HMGB1 mRNA in the SLE group were significantly higher than those in the HC group ,the differences were statistically significant (P< 0 .05) ,while the level of PBMCs RAGE mRNA had no statistical difference (P>0 .05);the Spearman correlation analysis showed that the level of plasma HMGB1 was positively correlated with antinuclear anti‐bodies titers and SLEDAI score in the SLE patients (P<0 .01) ,while had no obvious correlation with the other clinical and labora‐tory indicators(P>0 .05);the HMGB1 mRNA expression level was positively correlated with the RAGE mRNA expression level and SLEDAI scores(P<0 .01 ,P<0 .05) ,and had no obvious correlation with other clinical and laboratory indicators (P>0 .05) . Conclusion The abnormal expression of plasma HMGB1 and PBMCs HMGB1 mRNA in SLE patients prompts that which might be involved in the occurrence and development of SLE ,might participate in the immune and inflammatory regulation of SLE .