GLP-1 has a variety of anti-diabetic effects. However, native GLP-1 is not suitable for treatment of diabetes due to its short half-life (t½, 2-5 min). Exendin-4 is a polypeptide isolated from lizard saliva, which can bind to GLP-1 receptor, produce physiological effects similar to GLP-1, t½ up to 2.5 h, therefore, we developed a long-lasting GLP-1 receptor agonists and GLP-1-exendin-4 fusion IgG4 Fc [GLP-1-exendin-4/ IgG4(Fc)]. We constructed the eukaryotic expression vector of human GLP-1-exendin-4/IgG4(Fc)-pOptiVEC- TOPO by gene recombination technique and expressed the fusion protein human GLP-1-IgG4 (Fc) in CHO/DG44 cells. The fusion protein stimulated the INS-1 cells secretion of insulin, GLP-1, exendin-4 and fusion protein in CD1 mice pharmacokinetic experiments, as well as GLP-1, exendin-4 and fusion protein did anti-diabetic effect on streptozotocin induced mice. Results demonstrated that the GLP-1-exendin-4/IgG4(Fc) positive CHO/DG44 clones were chosen and the media from these positive clones. Western blotting showed that one protein band was found to match well with the predicted relative molecular mass of human GLP-1-exendin-4/IgG4(Fc). Insulin RIA showed that GLP-1-exendin-4/IgG4(Fc) dose-dependently stimulated insulin secretion from INS-1 cells. Pharmacokinetic studies in CD1 mice showed that with intraperitoneal injection (ip), the fusion protein peaked at 30 min in circulation and maintained a plateau for 200 h. Natural biological half-life of exendin-4 was (1.39 ± 0.28) h, GLP-1 in vivo t½ 4 min, indicating that fusion protein has long-lasting effects on the modulation of glucose homeostasis. GLP-1-exendin-4/IgG4(Fc) was found to be effective in reducing the incidence of diabetes in multiple-low-dose streptozotocin-induced diabetes in mice, longer duration of the biological activity of the fusion protein. The biological activity was significantly higher than that of GLP-1 and exendin-4. GLP-1-exendin-4/IgG4(Fc) has good anti-diabetic activity. It can be used as a long-acting GLP-1 agonists.
Animals ; CHO Cells ; Cricetinae ; Cricetulus ; Diabetes Mellitus, Experimental ; drug therapy ; Glucagon-Like Peptide 1 ; pharmacology ; Glucagon-Like Peptide-1 Receptor ; agonists ; Half-Life ; Humans ; Hypoglycemic Agents ; pharmacology ; Immunoglobulin G ; pharmacology ; Insulin ; secretion ; Mice ; Peptides ; pharmacology ; Recombinant Fusion Proteins ; pharmacology ; Venoms ; pharmacology

Animals ; Disease Models, Animal ; Ischemic Preconditioning ; methods ; Lung ; blood supply ; Male ; Nitric Oxide Synthase ; metabolism ; Nitroarginine ; pharmacology ; Rabbits ; Reperfusion Injury ; metabolism

Palmer-foot hyperhidrosis is one kind of focal hyperhidrosis, with symptoms of sweating hands or feet. Some people even have sweat dripping off their hands or feet. This article studied the views of TCM on palmer-foot hyperhidrosis, expounded the pathological and physiological relationship between palmer-foot hyperhidrosis and spleen and stomach, and proposed that clinical treatment should be based on the syndrome differentiation and treatment of spleen and stomach, which can achieve certain efficacy.

Adult ; Echinococcosis ; Heart Diseases ; parasitology ; Humans ; Male

Objective To explore the applicability of the abbreviated Chinese version of the social problem-solving inventory (C-SPSI) for nursing students in Shanghai. Methods The abbreviated C-SPSI was revised and 603 nursing students in Shanghai were surveyed by it, and the reliability and con-struct validity were evaluated by inter-item consistency analysis, test-retest reliability and principal factor analysis. Results The total CVI was 0.968. The construct validity was confirmed by factor analysis with 64.917% variance explained by four factors. The total Cronbach's α of C-SPSI was 0.897,and the total test-retest reliability coefficient was 0.781. Conclusions The abbreviated C-SPSI is an instrument with good reliability and validity and it can be used in assessing the nursing students' social problem-solving abilities and deficits.

Adenocarcinoma, Follicular ; diagnosis ; pathology ; Adenoma ; diagnosis ; pathology ; Carcinoma, Papillary ; diagnosis ; pathology ; Carcinoma, Papillary, Follicular ; diagnosis ; pathology ; Cell Nucleus ; pathology ; Diagnosis, Differential ; Humans ; Neoplasm Invasiveness ; Thyroid Gland ; pathology ; Thyroid Neoplasms ; diagnosis ; pathology ; Thyroid Nodule ; diagnosis ; Thyroiditis ; diagnosis

Nephrotic syndrome(NS)is the most frequent cause of glomerular disease in children,it can deve-lop many complications,including infection,thrombosis and acute kidney injury,while acute adrenocortical suppression is a complication of some drugs administration. This review focuses on the pathophysiology and management of common complications in patients with NS.

The influence of Chang-Bai Xin kui(长白新圭) on the acid ?-naPhthyl acetate esterase(ANAE) positive lymphocytes was studied by using ANAE as a cytochemical marker.S180 cells ef ascites tumor were inoculated into the mice in experimental and control group. 3 days later, 0.8mg/0.2ml of Chang-Bai Xin Kni was injected peritoneally into the mice in experimental group everyday in 7 days. Eaeh of the two groups has its own self control.The experimental results show that there is no significant differences in total numbar of ANAE positive lymphoctes between the two groups and all self-controls.But after 7 days of injecting the drug, the granular pattern and scattered granular pattern of lymphoctes were increased significantly(P

Objective To evaluate the diagnostic value for ankylosing spondylitis (AS).Methods Ninety-two patients with confirmed diagnosis of AS were allcated to Group A and 70 non-AS cases served as the control(Group B).Human leucocyte antigen B 27(HLA-B 27)was determined by micro-lymphocytoxicity test.Results The sensitivity and specificity of HLA-B 27 in diagnosing AS were 87.0% and 91.4% respectively.In a randomized human group,the morbidity rate of AS was 2.57% for those with HLA-B 27 being positive.In clinic,when the assumed morbidity rate of AS was 50%,the morbidity rate arrived at 91.01% for the cases of HLA-B 27 being positive.Conclusion HLA-B 27 is an important accessory diagnostic index for AS,but it can not be ued as a confirmed diagnostic index for AS.

Objective To compare the analgesia and side-effects of different concentrations of sufentanil combined with 0.125% ropivacaine for postoperative epidural analgesia after general thoracic surgery.Methods Thirty-six ASA Ⅰ-Ⅲ patients (25 males, 11 females) ages 21-64 yrs weighing 42-79 kg undergoing elective general thoracic surgery under general anesthesia were randomly assigned to receive patient-controlled epidural analgesia (PCEA) with 0.125% ropivacaine combined with sufentanil 0.4 (group A, n = 12) , 0.5 (group B, n = 12) or 0.6 ?g?ml-1 (group C, n = 12) . Epidural catheter was placed at T7,8 or T8,9 interspace. The PCEA pump was set up with back ground infusion of 2 ml?h-1 , a3ml bolus dose and a 30-min lock-out period. VAS scores was used to assess analgesia at rest and during movement. The total bolus doses, PCEA button pressing times (effective/actual), vital signs including MAP, HR, respiratory rate, SpO2 and side effects (nausea, vomiting, pruritus and dyspnea) were recorded. Results During the 48 hours after operation the VAS scores in group C were significantly lower than those in group A and B ( P