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.

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

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

Objective To investigate the current status and influencing factors of falls self-efficacy among the stroke elderly patients.Methods Totally 170 elderly stroke patients were investigated using the Modified Falls Efficacy Scale (MFES),and they were tested with Berg Balance Scale (BBS) and Time Up and Go Test (TUGT).Results The average score of falls self-efficacy was 108.There were 50.6％ elderly stroke patients assigned to the group with low falls self-efficacy.Multiple Logistic regression analysis indicated that impairments of balance and mobility,severe stroke-related disability were the independent influencing factors associated with FOF,which could explain 52.0％ of variations.Conclusions Low falls self-efficacy among the stroke elderly patients is a common complaint,nurses and physicians should focus on this problem,interventions combining exercise and education of accidental falls should be taken to improve falls self-efficacy of elderly stroke patients,and prevent falls finally.

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.

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.

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