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

Rehabilitation treatment after cerebral infarction establishes on the basis of plastic changes in the central nervous system,which can compensate the functions lost in the affected brain regions.Neurorehabilitation training realizes neurological function recovery partly by enhancing cortical reorganization.Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive approach that can effectively improve the cortical excitability,This article reviews the application of rTMS in the clinical studies of motor function recovery in patients with hemiplegia after cerebral infarction.

Owing to the profound impact of spinal cord injury, extensive studies have been carried out aimed at facilitating axonal regeneration following injury. Tissue engineering, as an emerging and rapidly growing field, has received extensive attention for nervous system axonal guidance. Numerous engineered substrates including biomaterial scaffolds, cells, biomolecules, have showed potential of supporting axonal regeneration and functional recovery. This article reviews current progresses on biomaterial scaffolds, cells, biomolecules for nerve repair, as well as therapeutic approaches that are being explored for spinal cord repairing.

Thin basement membrane nephropathy(TBMN) is one of the most common disorders of the kidney,affecting at least 1% of the population.It seems to be a disease of the adult glomerular basement membrane(GBM) type Ⅳ collagen trimer ?3∶?4∶?5.Genetic evidence indicates that autosomal TBMN is caused by heterozygous mutations in either COL4A3 or COL4A4, whereas homozygous or combined heterozygous mutations in the same genes lead to autosomal recessive Alport syndrome.The author summarized the epidemiology,clinical features,renal biopsy,genetics,pathogenesis,diagnosis and therapy of TBMN.

Objective To establish the quality standard of Xiao'er resuqing gantules.Methods Rhei Radix et Rhizoma,Bupleuri Radix,Forsythiae Fructus,Puerariae Lobatae Radix in the granules were qualitatively identified by the method of thin layer chromatography (TLC).The content of baicalin was analyzed by the method of high performance liquid chromatography (HPLC).Results There were good specificities of the TLC method to identify Rhei Radix et Rhizoma,Bupleuri Radix,Forsythiae Fructus,Puerariae Lobatae Radix.The linear range of baicalin was 0.116 2-1.743 0 μg (r =1.000 0).The average of recovery and RSD were 100.61％,0.79％ (n =6),respectively.Conclusion The method established in this study is simple,accurate,reliable and suitable to be applied to quality control for the preparation of Xiao' er resuqing granules.

Anemia, Aplastic ; therapy ; Humans ; Immunosuppression ; Retrospective Studies

ObjectiveTo investigate the clinical phenotypes of familial hypercholesterolemia (FH) caused by exon 13 A606T mutation in low deusity lipoprotein receptor.MethodsClinical data of the suffered family were collected and analyzed,as well as measurement of perivascular intima-medial thickness and follow-mediated-dilation function by ultrasonography.ResultsThere were totally 11 sufferers including 4 males and 9 females,aged 8-90 years,with 2 homozygotes and 9 heterozygotes.Among them, one homozygote showed angina pectoris and hematuria,both homozygotes had skin xanthomata.TC,TG,LDL-C and HDL-C were(7.39 ± 1.30) mmol/L,(0.93 ± 0.36) mmol/L,( 11.76 ± 1.10) mmol/L and ( 1.22 ±0.17) mmol/L,respectively.The left/right sided intima-medial thickness of the common,internal,external and bulb carotid artery were ( 1.15 ±0.45) mm/( 1.30 ±0.60) mm,(0.82 ±0.30) mm/( 1.00 -0.66)mm,(0.77 ±0.28) mm/(0.78 ±0.30) mm and ( 1.40 ±0.59) mm/( 1.46 ±0.71 ) mm respectively.The brachial artery flow mediated dilation rate was (4.85 ±4.80)％.Echocardiography revealed 2 patients with cardiac valvular disease and 3 with atrium septum aneurysm. ConclusionFH patients show a variety of phenotypes incuding extraordinary hypercholesterolemia,subcutaneous xanthomata and premature coronary heart disease.

Objective:To study the fingerprint of Radix Salviae Miltiorrhizae of Xiangdan Injection. Methods : HPLC with UV detector was used to analyze the patterns of the Radix Salviae Miltiorrhizae of Xiangdan Injection. Protocatechuic aldehyde was used as internal standard substance. Results : The fingerprint of Radix Salviae Miltiorrhizae of Xiangdan Injection was set up and the fingerprint of them showed an excellent correlation. Conclusion : The study is helpful for the quality control of Xiangdan Injection.

Esophageal and Gastric Varices ; complications ; prevention & control ; surgery ; Gastrointestinal Hemorrhage ; complications ; prevention & control ; surgery ; Humans

Adult ; Antibodies, Monoclonal, Murine-Derived ; administration & dosage ; therapeutic use ; Female ; Hemophilia A ; drug therapy ; Humans ; Rituximab