1.Standardization of clinical application of mass spectrometry method for measurement of vitamin D in capillary blood of children: a multicenter study.
Luan Luan LI ; Xiao Nan LI ; Fei Yong JIA ; Mei Zhu CHI ; Zhi Hong WEN ; Fan YANG ; Yu Ning LI ; Li Jun HA ; Ying YANG ; Xiao Ling LONG ; Shuan Feng FANG ; Lu XIE ; Hui Feng ZHANG ; Xiaodan YU
Chinese Journal of Pediatrics 2022;60(12):1282-1287
		                        		
		                        			
		                        			Objective: To establish the norms and clinical application standards of mass spectrometry method to measure vitamin D in capillary blood. Methods: Following the "Province-City-Hospital" sampling procedure, a cross-sectional sample of 1 655 healthy children under 7 years of age were recruited from 12 provinces, autonomous regions, or municipalities in China from November 2020 to December 2021. Both venous and capillary blood samples from the same individual were collected, for which serum 25(OH)D levels were measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method. Pearson correlation analysis and linear regression analysis were used to detect the correlation and determine a correction algorithm. The agreement was analyzed using Bland-Altman plot and Kappa statistic. The sensitivity and specificity were evaluated using receiver operating characteristic (ROC) curve method. Results: Venous and capillary 25(OH)D levels of 1 655 healthy children under 7 years of age were 74.25 (59.50, 92.00) and 68.75 (54.44, 86.25) nmol/L, respectively, showed a significant difference(Z=22.14, P<0.001) as well as a highly significant correlation between venous and capillary 25(OH)D levels(r=0.95, P<0.001). Linear regression analysis was then performed to determine the correction algorithm: lg(corrected capillary 25(OH)D)=0.13+0.95×lg(capillary 25(OH)D)(R2=0.90,P<0.001). The deviation between venous and corrected capillary 25(OH)D levels was (0.50±17.50) nmol/L, a difference value that did not reach statistical significance (P>0.05). The cut-off values of capillary blood 25(OH)D values 30.00, 50.00, 75.00 nmol/L corresponding to venous blood 25(OH)D values were 26.59, 45.56, and 69.84 nmol/L, respectively. Good consistency was observed between venous and corrected capillary 25(OH)D levels in clinical diagnosis (Kappa value 0.68-0.81). Corrected capillary 25(OH)D showed a high clinically predictive value (area under curve 0.97-0.99,sensitivity 0.72-0.92,specificity 0.89-0.99). Conclusion: The standardized capillary HPLC-MS/MS method can be used to detect 25(OH)D levels in children clinically.
		                        		
		                        		
		                        		
		                        			Child
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Vitamin D
		                        			;
		                        		
		                        			Cross-Sectional Studies
		                        			;
		                        		
		                        			Tandem Mass Spectrometry
		                        			;
		                        		
		                        			Vitamins
		                        			;
		                        		
		                        			Reference Standards
		                        			
		                        		
		                        	
2.Analysis of vitamin D status among children under 7 years of age in some regions of China.
Luan Luan LI ; Xiao Nan LI ; Fei Yong JIA ; Mei Zhu CHI ; Zhi Hong WEN ; Fan YANG ; Yu Ning LI ; Li Jun HA ; Ying YANG ; Xiao Ling LONG ; Shuan Feng FANG ; Hui Feng ZHANG ; Xiao Dan YU
Chinese Journal of Pediatrics 2022;60(5):413-420
		                        		
		                        			
		                        			Objective: To explore current vitamin D status and influential factors of vitamin D deficiency and insufficiency among children under 7 years of age in 11 provinces, autonomous regions or municipalities of China. Methods: According to the "province-city-hospital" sampling technical route, a total of 1 531 healthy children under 7 years of age were sampled from 11 provinces, autonomous regions or municipalities in China by the cluster random sampling method from November 2020 to November 2021. The demographic information, family conditions, behavior and living habits and feeding behaviors were collected using unified questionnaire. Serum 25-hydroxyvitamin D(25(OH)D) levels were measured by liquid chromatography-tandem mass spectrometry. Serum 25(OH)D<30 nmol/L was considered deficient and 30-50 nmol/L was considered insufficient. With 25(OH)D≤50 nmol/L as the dependent variable, multivariate Logistic regression was applied to analyze the association between vitamin D deficiency and insufficiency and potential influential factors. Results: The prevalence of vitamin D deficiency and insufficiency among children under 7 years of age in 11 provinces, autonomous regions or municipalities of China was 14.0% (215/1 531), 3.8% (25/664) and 21.9% (190/867) in 0-<3 and 3-<7 of age years, respectively. Compared to children aged 0-<3 years, children aged 3-<7 years had a 2.6-fold increased risk of vitamin D deficiency and insufficiency (OR=3.60, 95%CI 1.93-6.72, P<0.001). Frequent sunlight exposure (OR=0.46, 95%CI 0.29-0.73, P=0.001), vitamin D supplementation (sometimes, OR=0.33, 95%CI 0.21-0.51, P<0.001; daily, OR=0.20, 95%CI 0.11-0.36, P<0.001) and infant formula intake(4-7 times per weeks, OR=0.43, 95%CI 0.28-0.68, P<0.001) were protective factors for vitamin D deficiency and insufficiency. Conclusion: Vitamin D deficiency and insufficiency are common among children under 7 years of age in 11 provinces, autonomous regions or municipalities of China, which is affected by age, sunlight exposure, vitamin D supplementation and infant formula intake.
		                        		
		                        		
		                        		
		                        			Child
		                        			;
		                        		
		                        			China/epidemiology*
		                        			;
		                        		
		                        			Cross-Sectional Studies
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Infant
		                        			;
		                        		
		                        			Vitamin D
		                        			;
		                        		
		                        			Vitamin D Deficiency/epidemiology*
		                        			;
		                        		
		                        			Vitamins
		                        			
		                        		
		                        	
3. Individualized treatment of intraventricular hemorrhage guided by modified Graeb criteria score and Glasgow coma scale
Fei LONG ; Kunming QIN ; Shengchao LIAO ; Jingzhan WU ; Chunhai TANG ; Tao LIU
Chinese Critical Care Medicine 2019;31(11):1373-1377
		                        		
		                        			 Objective:
		                        			To investigate the clinical effect of modified Graeb criteria score and Glasgow coma score (GCS) in individualized treatment of intraventricular hemorrhage.
		                        		
		                        			Methods:
		                        			113 patients with intraventricular hemorrhage admitted to the department of neurosurgery of Second Affiliated Hospital of Guangxi Medical University from June 2014 to February 2018 were enrolled, and they were divided into 13-15, 9-12, and 3-8 groups according to GCS score at admission, and modified Graeb criteria score was classified as grade Ⅰ, Ⅱ and Ⅲ at the same time. In GCS 9-12 and 3-8 groups, patients with modified Graeb criteria score grade Ⅲ were treated with bilateral extra ventricular drainage, patients with modified Graeb criteria score grade Ⅱ were treated with bilateral extra ventricular drainage or lumbar cistern drainage (GCS 9-12 group was more prior to lumbar cistern drainage, 3-8 group was given priority to extra ventricular drainage), and patients with modified Graeb criteria score grade Ⅰ were treated conservatively. In GCS 13-15 group, bilateral extra ventricular cerebral drainage or lumbar cistern drainage was performed if the modified Graeb criteria score grade was Ⅲ, lumbar cistern drainage or conservative treatment was performed if the modified Graeb criteria score grade was Ⅱ, and conservative treatment was performed if the modified Graeb criteria score grade was Ⅰ. The changes in GCS score at 1 month after individualized treatment and the favourable prognosis rate at 6 months after treatment were observed [favourable prognosis was defined as Glasgow outcome score (GOS) Ⅳ-Ⅴ] as well as the basic clearance time of intraventricular hematomas, and the occurrence of complications such as intracranial infection, pulmonary infection and hydrocephalus were recorded.
		                        		
		                        			Results:
		                        			113 patients with intraventricular hemorrhage were enrolled in the final analysis, including 39 patients in GCS 13-15 group, 27 in 9-12 group, and 47 in 3-8 group; 21 patients with the first grade of modified Graeb criteria score, 42 with the second grade and 50 with the third grade. At 1 month after individualized treatment, the GCS scores in GCS 13-15 and 9-12 groups were significantly higher than those at admission (14.8±0.2 vs. 13.7±0.8, 13.1±1.7 vs. 10.7±1.1, both 
		                        		
		                        	
4.Individualized treatment of intraventricular hemorrhage guided by modified Graeb criteria score and Glasgow coma scale.
Fei LONG ; Kunming QIN ; Shengchao LIAO ; Jingzhan WU ; Chunhai TANG ; Tao LIU
Chinese Critical Care Medicine 2019;31(11):1373-1377
		                        		
		                        			OBJECTIVE:
		                        			To investigate the clinical effect of modified Graeb criteria score and Glasgow coma score (GCS) in individualized treatment of intraventricular hemorrhage.
		                        		
		                        			METHODS:
		                        			113 patients with intraventricular hemorrhage admitted to the department of neurosurgery of Second Affiliated Hospital of Guangxi Medical University from June 2014 to February 2018 were enrolled, and they were divided into 13-15, 9-12, and 3-8 groups according to GCS score at admission, and modified Graeb criteria score was classified as grade I, II and III at the same time. In GCS 9-12 and 3-8 groups, patients with modified Graeb criteria score grade III were treated with bilateral extra ventricular drainage, patients with modified Graeb criteria score grade II were treated with bilateral extra ventricular drainage or lumbar cistern drainage (GCS 9-12 group was more prior to lumbar cistern drainage, 3-8 group was given priority to extra ventricular drainage), and patients with modified Graeb criteria score grade I were treated conservatively. In GCS 13-15 group, bilateral extra ventricular cerebral drainage or lumbar cistern drainage was performed if the modified Graeb criteria score grade was III, lumbar cistern drainage or conservative treatment was performed if the modified Graeb criteria score grade was II, and conservative treatment was performed if the modified Graeb criteria score grade was I. The changes in GCS score at 1 month after individualized treatment and the favourable prognosis rate at 6 months after treatment were observed [favourable prognosis was defined as Glasgow outcome score (GOS) IV-V] as well as the basic clearance time of intraventricular hematomas, and the occurrence of complications such as intracranial infection, pulmonary infection and hydrocephalus were recorded.
		                        		
		                        			RESULTS:
		                        			113 patients with intraventricular hemorrhage were enrolled in the final analysis, including 39 patients in GCS 13-15 group, 27 in 9-12 group, and 47 in 3-8 group; 21 patients with the first grade of modified Graeb criteria score, 42 with the second grade and 50 with the third grade. At 1 month after individualized treatment, the GCS scores in GCS 13-15 and 9-12 groups were significantly higher than those at admission (14.8±0.2 vs. 13.7±0.8, 13.1±1.7 vs. 10.7±1.1, both P < 0.05). When comparing the GCS score of the same patient at admission with that of 1 month after treatment, the GCS scores of the three groups were significantly improved, indicating that the consciousness of patients with different coma levels at admission had been significantly improved after individualized treatment. The basic clearance time of intracerebroventricular hematomas in patients with the second grade of modified Graeb criteria score was (7.0±2.8) days, in patients with the third grade was (6.1±2.0) days. At 6 months after individualized treatment, among 113 patients, GOS score was grade I in 7 patients (6.2%), grade II in 13 patients (11.5%), grade III in 28 patients (24.8%), grade IV in 27 patients (23.9%), and grade V in 38 patients (33.6%), with the favourable prognosis rate of 57.5% (65/113). Among 113 patients, intracranial infection occurred in 5 patients (4.4%), pulmonary infection in 22 patients (19.5%), hydrocephalus in 2 patients (1.8%) and rebleeding in 4 patients (3.5%). In 83 patients with lumbar cistern drainage, 1 patient had post-drainage infection (1.2%), 3 patients had plugging (3.6%), 6 patients had accidental drop of drainage tube (7.2%), and none of them had occipital macroforamen hernia after drainage. Seven of the 113 patients died including 2 patients died of cerebral hernia caused by rebleeding, 5 patients died of severe pneumonia or automatic discharge from hospital.
		                        		
		                        			CONCLUSIONS
		                        			The combination of modified Graeb criteria score and GCS score can individualize treatment for patients with intraventricular hemorrhage and effectively improve the prognosis of patients with intraventricular hemorrhage.
		                        		
		                        		
		                        		
		                        			Cerebral Hemorrhage
		                        			;
		                        		
		                        			China
		                        			;
		                        		
		                        			Glasgow Coma Scale
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hydrocephalus
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Treatment Outcome
		                        			
		                        		
		                        	
5.The long lasting effect of the murine fibroblast growth factor-21 on blood glucose control of diabetic animals.
Jing-Zhuang ZHAO ; Guo-Peng SUN ; Xian-Long YE ; Jin-Nan LI ; Gui-Ping REN ; Wen-Fei WANG ; Ming-Yao LIU ; De-Shan LI
Acta Pharmaceutica Sinica 2013;48(3):352-358
		                        		
		                        			
		                        			Insulin is the most common medicine used for diabetic patients, unfortunately, its effective time is short, even the long-acting insulin cannot obtain a satisfactory effect. Fibroblast growth factor (FGF)-21 is a recently discovered glucose mediator and expected to be a potential anti-diabetic drug that does not rely on insulin. In this study, db/db mice were used as the type 2 diabetic model to examine whether mFGF-21 has the long-term blood lowering effect on the animal model. The results showed that mFGF-21 could stably maintain the blood glucose at normal level for a long-term in a dose-dependent manner. Administration of mFGF-21 once a day with three doses (0.125, 0.25 and 0.5 mg x kg(-1)) could maintain blood glucose of the model animals at normal level for at least 24 h. Administration of mFGF-21 every two days with the same doses could maintain blood glucose of the model animals at normal level for at least 48 h, although it took longer time for blood glucose to reach to normal level depending on doses used (twenty injections for 0.125 mg x kg(-1) and 0.25 mg x kg(-1) doses, ten injections for 0.5 mg x kg(-1) dose). Surprisingly, the blood glucose of the treated model animals still maintained at normal level for 24 h after the experiment terminated. Glycosylated hemoglobin level of the animals treated with mFGF-21, which represented long-term glucose status, decreased significantly compared to the control group and the insulin group. The results suggest that FGF-21 has potential to become a long-acting and potent anti-diabetic drug.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Blood Glucose
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Diabetes Mellitus, Experimental
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Dose-Response Relationship, Drug
		                        			;
		                        		
		                        			Fibroblast Growth Factors
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			pharmacology
		                        			;
		                        		
		                        			Glucose Transporter Type 1
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Glucose Transporter Type 4
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Glycated Hemoglobin A
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Hypoglycemic Agents
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			pharmacology
		                        			;
		                        		
		                        			Liver
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Mice
		                        			
		                        		
		                        	
6.Therapeutic effect of fibroblast growth factor 21 on hypertension induced by insulin resistance.
Sheng-long ZHU ; Gui-ping REN ; Zhen-yu ZHANG ; Wen-fei WANG ; Xian-long YE ; Miao-miao HAN ; Jing-zhuang ZHAO ; Tong-yu XU ; Ming-yao LIU ; De-shan LI
Acta Pharmaceutica Sinica 2013;48(9):1409-1414
		                        		
		                        			
		                        			This study is to evaluate the therapeutic effect of fibroblast growth factor 21 (FGF21) on hypertension induced by insulin resistance in rats and to provide mechanistic insights into its therapeutic effect. Male Sprague-Dawley (SD) rats were fed with high-fructose (10%) water to develop mild hypertensive models within 4 weeks, then randomized into 4 groups: model control, FGF21 0.25, 0.1 and 0.05 micromol x kg(-1) x d(-1) groups. Five age-matched normal SD rats administrated with saline were used as normal controls. The rats in each group were treated once a day for 4 weeks. Body weight was measured weekly, systolic blood pressure (SBP) was measured noninvasively using a tail-cuff method, insulin sensitivity was assessed using oral glucose tolerance test (OGTT) and HOMA-IR assay. At the end of the treatment, blood samples were collected, and blood glucose, serum cholesterol, serum triglyceride and serum insulin were measured. The results showed that blood pressure of the rats treated with different doses of FGF21 returned to normal levels [(122.2 +/- 3.5) mmHg, P < 0.01] after 4-week treatment, whereas, SBP of untreated (model control) rats maintained a high level [(142.5 +/- 4.5) mmHg] throughout the treatment. The observation of blood pressure in 24 h revealed that SBP of FGF21 treated-rats maintained at (130 +/- 4.5) mmHg vs. (143 +/- 5.5) mmHg for model control (P < 0.01). FGF21 treatment groups improved serum lipids obviously, total cholesterol (TC) and triglyceride (TG) levels decreased significantly to normal levels. The serum NO levels of three different doses FGF21 treatment group were significantly higher than that of the model control group [(7.32 +/- 0.11), (7.24 +/- 0.13), (6.94 +/- 0.08) vs. (6.56 +/- 0.19) micromol x L(-1), P < 0.01], and the degree of improvement showed obvious dose-dependent manner, indicating that FGF21 can significant increase serum NO in fructose-induced hypertension rat model and improve endothelial NO release function. The results of OGTT and HOMA-IR showed that insulin resistance state was significantly relieved in a dose-dependent manner. Thus, this study demonstrates that FGF21 significantly ameliorates blood pressure in fructose-induced hypertension model by relieving insulin resistance. This finding provides a theoretical support for clinical application of FGF21 as a novel therapeutics for treatment of essential hypertension.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Antihypertensive Agents
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Blood Glucose
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Blood Pressure
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			Body Weight
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			Cholesterol
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			Dose-Response Relationship, Drug
		                        			;
		                        		
		                        			Fibroblast Growth Factors
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Fructose
		                        			;
		                        		
		                        			Glucose Tolerance Test
		                        			;
		                        		
		                        			Hypertension
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			chemically induced
		                        			;
		                        		
		                        			drug therapy
		                        			;
		                        		
		                        			Insulin Resistance
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Nitric Oxide
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			Rats
		                        			;
		                        		
		                        			Rats, Sprague-Dawley
		                        			;
		                        		
		                        			Triglycerides
		                        			;
		                        		
		                        			blood
		                        			
		                        		
		                        	
7.Clinical outcomes of "All-on-4" immediate-function report of 10 cases
Hai-Peng SUN ; Xiu-Mei ZHUANG ; Hai-Bin SHAO ; Zhan-Peng LIAO ; Fei-Long DENG
Chinese Journal of Stomatology 2013;48(z1):40-44
		                        		
		                        			
		                        			Objective To retrospectively evaluate the clinical and radiographic outcomes of immediately loaded full-arch fixed prostheses with All-on-4 concept after 1 year and 3 years of function.Methods A total of 40 dental implants were placed in ten edentulous patients(3 in maxilla,7 in mandible).Follow-up examinations were performed at 6 months,12 months,and thereafter every 12 months.Radiographic assessment of the marginal bone level was performed after 1 and 3 years in function.The marginal bone resorption was compared between tilted and axial implants.Results The success rate of implants was 100% (40/40) and 97% (37/38) after 1 and 3 years,respectively.The success rate of prostheses were both 100%.37 after 1 and 3 years.The marginal bone resorption was,on average,(0.96 ±0.25) and (1.48 ± 0.20) mm after 1 and 3 years,respectively.The difference of marginal bone resorption between tilted implants and axial implants was not statistically significant (P > 0.05) after 1 year or after 3 years.Implants presented heahhy peri-implant soft tissue conditions.Conclusions The clinical outcome of edentulous immediate rehabilitation supported by 4 implants was satisfactory after 1 and 3 years in function.
		                        		
		                        		
		                        		
		                        	
8.Construction of recombinant lentiviral vectors containing Rheb gene and its mutant Rheb'D60K gene and their expression in human liver cancer cells.
Ke-He CHEN ; Bo LIANG ; Zhen-Hong ZOU ; Ze-Long HAN ; Jin-Fei PAN ; An-Ling LIU
Journal of Southern Medical University 2012;32(3):341-344
OBJECTIVETo construct recombinant lentiviral vectors carrying Rheb gene and its mutant Rheb'D60K gene, and examine their expression in human liver cancer cells.
METHODSRheb gene was amplified by PCR to construct the recombinant plasmid LV31-Rheb-WT and LV31-Rheb-D60K. HEK-293 FT cells were contransfected with the recombinant lentiviral vector together with a lentiviral package plasmid to produce the lentiviral particles. The expression of PS6 protein was detected in the lentivirus-infected MCF-7 cells. The apoptosis of SK-HEP-1 cells transfected with LV31-Rheb-WT or LV31-Rheb-D60K was observed.
RESULTSThe recombinant LV31-Rheb-WT and LV31-Rheb-D60K vectors were confirmed by PCR and DNA sequencing. Western blotting showed that PS6 protein expression was increased in LV31-Rheb-WT-transfected cells while decreased in LV31-Rheb-D60K-transfected cells. LV31-Rheb-D60K-transfected SK-HEP-1 cells showed more obvious apoptosis after starvation than LV31-Rheb-WT-transfected cells.
CONCLUSIONLentiviral vectors carrying Rheb gene and its mutant has been successfully constructed, which can be useful in further investigation of the role of Rheb gene in cancer cells.
Apoptosis ; genetics ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Genetic Vectors ; genetics ; HEK293 Cells ; Humans ; Lentivirus ; genetics ; metabolism ; Liver Neoplasms ; metabolism ; pathology ; MCF-7 Cells ; Monomeric GTP-Binding Proteins ; biosynthesis ; genetics ; Mutant Proteins ; genetics ; Neuropeptides ; biosynthesis ; genetics ; Ras Homolog Enriched in Brain Protein ; Recombinant Proteins ; biosynthesis ; genetics ; Transfection
9.Papillae alterations around single-implant restorations in the anterior maxillae: thick versus thin mucosa.
Mi-Si SI ; Long-Fei ZHUANG ; Xin HUANG ; Ying-Xin GU ; Chung-Hao CHOU ; Hong-Chang LAI
International Journal of Oral Science 2012;4(2):94-100
		                        		
		                        			
		                        			To evaluate the papilla alterations around single-implant restorations in the anterior maxillae after crown attachment and to study the influence of soft tissue thickness on the papilla fill alteration. According to the inclusion criteria, 32 patients subjected to implant-supported single-tooth restorations in anterior maxillae were included. The patients were assigned to two groups according to the mucosal thickness: (i) group 1, 1.5 mm s mucosal thickness 3 mm; and (ii) group 2, 3 mm
10.Optimization and characterization of a novel FGF21 mutant.
Xian-Long YE ; Hua-Shan GAO ; Wen-Fei WANG ; Gui-Ping REN ; Ming-Yao LIU ; Kun HE ; Ya-Kun ZHANG ; Jing-Zhuang ZHAO ; Dan YU ; De-Shan LI
Acta Pharmaceutica Sinica 2012;47(7):897-903
		                        		
		                        			
		                        			Fibroblast growth factor 21 (FGF21) is a member of FGF family. It has been demonstrated that FGF21 is an independent, safe and effective regulator of blood glucose levels in vivo. In order to improve the activity of FGF21, we exchanged the beta10-beta12 domain of the human FGF21 with that of the mouse FGF21 to construct a novel FGF21 gene (named hmFGF21), and then subcloned hmFGF21 gene into the SUMO expression vector to create pSUMO-hmFGF21 and transformed it into E. coli Rosetta for expression of the fusion protein SUMO-hmFGF21. Both in vitro and in vivo glucose regulation activity of hmFGF21 was evaluated. The SDS-PAGE result showed that compared with wild-type hFGF21, the soluble expression of hmFGF21 increased about 2-fold. HmFGF21 was more potent in stimulation of glucose uptake in HepG2 cells in vitro. The results of anti-diabetic effect on db/db mice demonstrated that hmFGF21 had better efficacy on controlling the blood glucose of the db/db diabetic animals than wild-type hFGF21. These results suggest that the biological properties of FGF21 are significantly improved by optimization.
		                        		
		                        		
		                        		
		                        			Amino Acid Sequence
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Blood Glucose
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Cysteine Endopeptidases
		                        			;
		                        		
		                        			Diabetes Mellitus, Experimental
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			Endopeptidases
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Escherichia coli
		                        			;
		                        		
		                        			Fibroblast Growth Factors
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			pharmacology
		                        			;
		                        		
		                        			Genetic Vectors
		                        			;
		                        		
		                        			Glucose
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Hep G2 Cells
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hypoglycemic Agents
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			pharmacology
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Mutation
		                        			;
		                        		
		                        			Plasmids
		                        			;
		                        		
		                        			Recombinant Fusion Proteins
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			pharmacology
		                        			;
		                        		
		                        			Transformation, Genetic
		                        			
		                        		
		                        	
            
Result Analysis
Print
Save
E-mail