The high and continuing soaring incidence of diabetes may become a huge obstacle to China's development. The antidiabetic drug development is one way to solve the problem. Animal model is a powerful tool for drug development. This paper compares and analyzes the three kinds of animal models for antidiabetic drug development in replicating principle, methods and characteristic, then summarized the application in the research of traditional Chinese medicine. At the same time, the analysis of the market, application and clinical advantages of hypoglycemic medicine from traditional Chinese medicine, is given in this paper, based on the literature analysis. From the point of the clinic advantage embodiment and new drug development, this paper will provide advisory and assistance support for the anti-diabetic fighting with traditional Chinese medicine.
Animals ; China ; Diabetes Mellitus ; drug therapy ; Disease Models, Animal ; Drug Discovery ; Humans ; Hypoglycemic Agents ; Medicine, Chinese Traditional

Purpose To study the effect of overexpressing either wild type or a familial Alzheimer disease mutant presenilin 1 (mPS1) on tau phosphorylation in neuroblastoma NG-108 cells. Methods Three different plasmids transfected NG-108 cells respectively. Immunostaining and confocal microscopic technique were used to study the distribution of presenilin 1 and phosphorylated tau. Immunoblot test was applied to investigate the change of tau phosphorylation. Results Immunostaining showed that in brain of sporadic Alzheimer disease, PS1 mainly distributed in neuron and partially colocalized with the phosphorylated tau. Immunoblot tests showed that the cells transected either wild type PS1 or mPS1 contained more phorphorylated tau than the control cells. However, MTT test showed no significant difference between mock transfected cells and the wPS1 or mPS1 transfected cells. In addition, after transfection of the constructed PS1-EGFP vector, overexpressed EGFP-PS1 was located at cell surface membrane and subcellular organelles at earlier time at 12 hr, then EGFP-PS1 diffused in cytosol. Immunocytochemical observations demonstrated that some of the PS1-EGFP transfected cells contained more phosphorylated tau protein, which formed aggresome with PS-1-EGFP. When treated with phosphotase inhibitor okadaic acid, in the PS1-EGFP transfected cells accumulated more phosphorylated tau than the un-transfected cells. Conclusions Wild type PS1 is possibly involved in tauopathy in sporadic Alzheimer's disease.

Objective To investigate the feasibility and clinical value of double-balloon endoscopy in subjects of failed conventional colonoseopy and gastro-intestinal tract modified surgery.Methods Doubleballoon endoscopy was performed in thirty-two subjects of failed conventional colonoscopy,three and nine patients of previous subtotal gastrectomy with BillrothⅡand gastro-intestinal modified surgery for various clinical manifestations.Suceessful intubation rates of terminal ileum or cecum in colonoscopic failure patients,afferent and efferent loop intubation in patients of BillrothⅡand alimentary tract modified surgery,were recorded and diagnostic yields in these patients were also observed.Results The endoscopy was successfully intubated into terminal ileum or cecum in 29 subjects,the intubated rate was 90.6%,the endoscopic diagnosis was obtained in 7 subjects,and endoscopic treatment was performed in 3 subjects.The endoscopy was successfully inserted in terminus of afferent loop and 150-180 cm of efferent below the anastomosis in all 3 patients of Billroth type Ⅱ gastrectomy,and the diagnosis was all clarified.And endoscopic retrograde cholangiopancreatography was performed in one patient.Five of nine patients with previous alimentary tract modified surgery had lesions detected after endoscopic procedure,and double-balloon endoscopy could have a thorough visualization on operated area and suspected region as needed.Abdominal pain and melaena were observed in 8 and 3 subjects respectively.Transient urine amylase elevation was found in one patient.The symptoms were alleviated and amylase was returned to normal after treatment.Conclusions Double-balloon endoscopy was a safe and feasible remediai endoscopic procedure with high diagnostic yields and endotherapeutic interventional capability,in patients of failed conventional colonoscopy and previous BillrothⅡgastrectomy and alimentary modified surgery.

AIM:To investigate the effects of MG132,one of the proteasomal peptide aldehydes inhibitors,on lipopolysaccharide(LPS)-induced nuclear transcription factor-kappa B(NF-?B) activation,the production of nitric oxide(NO) and tumor necrosis factor-alpha(TNF-?),as well as the expression of inducible nitric oxide synthase(iNOS) in murine macrophage line RAW264.7.METHODS:Reporter gene assay was used to examine the activity of NF-?B by pNiFty-SEAP/HEK293 cells,which were transfected with the pNiFty reporter plasmid into human embryo kidney cells(HEK293).Fluorescence substrate DAF-2DA was used to testify NO level in Raw264.7 cell line induced by LPS.Furthermore,the secretion of TNF-? was examined by ELISA.Western blotting was used to reveal the expression of iNOS and I?B-?.RESULTS:MG132 significantly decreased the secretion of TNF-? induced by LPS,with the inhibitory rates of 36.7% and 60.4% to 5 ?mol/L and 10 ?mol/L MG132,respectively.The pro-inflammatory mediator NO production was decreased in a dose-dependent manner with the inhibitory rates increasing from 29.5%(2 ?mol/L) to 55.9%(10 ?mol/L).Pretreatment with MG132 reduced the expression of iNOS,but restored the I?B restrain caused by LPS treatment.Observed by a reporter gene assay,TNF-?-induced NF-?B activity was decreased gradually by addition of increasing concentration of MG132(2.5-10 ?mol/L).CONCLUSION:Our results suggest an anti-inflammation effect of MG132 by the suppression of LPS-induced the production of pro-inflammatory mediators including NO and TNF-?,and the expression of iNOS,which probably mediates the blockage of I?B degradation and NF-?B activation.

Objective To explore a method for development of carbon tetrachloride-induced cirrhotic model in rabbit and establish a portal vein delivery system in this model.Methods Male New Zealand white rabbit was subcutaneously injected carbon tetrachloride twice weekly,and the liver pathology and hepatic hydroxyproline content were examined after 12 weeks of injection.Portal vein catheterization was introduced through the terminal branch of mesostenium vein.The injection end of the catheter was embedded subcutaneously in the abdominal wall of the animal.The portal delivery was implemented by percutaneous puncture of the injection cap.Results After 12 weeks' of carbon tetrachloride administration,the rabbit liver developed typical pseudo lobule,and the liver hydroxyproline content increased 3.5 times compared to normal control.The portal vein delivery system could be maintained as long as 12 weeks.Conclusion A successive method to induce rabbit liver cirrhosis is developed,and a simple and economic animal portal vein delivery system is introduced.

Objective To analyze the dietary habits, energy intake and expenditure, anthropometrics, and body composition of the outpatients visiting the weight loss clinic of Beijing Hospital.Methods We pro-spectively enrolled 89 consecutive patients with body mass index ( BMI) ≥24 kg/m2 from November 2014 to August 2015 in the weight loss clinic of Beijing Hospital.There were 35 male and 54 female, with the mean age of (45.8 ±16.4) years.We divided them into two groups:the diabetes group (n=35) and the non-diabetes group (n=54), and compared the dietary habits, energy intake and expenditure, anthropometrics and body composition between the two groups.Results Regardless of diabetes, the overweight and obese patients all ate fast, mostly finishing a meal in about 10 minutes.They preferred Chinese food and meat, and disliked hot food.The frequency of dinning out in the non-diabetes group (3-5 times per week) was higher than that in the diabetes group (1-2 times per week) .Compared with the diabetes group, the non-diabetes group had higher fat-to-energy ratio [(34.9 ±7.6)%vs.(30.8 ±5.9)%], but lower carbohydrate intake [(232.2 ±59.7) g vs.(283.6 ±89.5) g], carbohydrate-to-energy ratio [ (47.9 ±8.3)%vs.(53.4 ±7.1)%], and the ratio of resting metabolic rate to body weight [ (66.9 ±9.6) kJ/(d? kg) vs.(71.1 ±7.9) kJ/(d? kg)] (all P<0.05).There were no statistically significant differences between the two groups in total energy intake, pro-tein intake, high quality protein intake, fat intake, protein-to-energy ratio, and resting metabolic rate (all P>0.05).Anthropometrics showed that the mean BMI of the patients was (32.8 ±4.4) kg/m2, with the maxi-mum being 53.5 kg/m2.The hip circumference [ (117.15 ±9.9) cm vs.(111.1 ±8.2) cm], upper arm circumference [ (36.4 ±3.8) cm vs.(34.0 ±3.3) cm], and triceps skinfold thickness [ (36.1 ±8.9) mm vs.(31.6 ±8.8) mm] were larger in the non-diabetes group than in the diabetes group (all P<0.05), but the mean age was lower in the non-diabetes group [ (41.7 ±16.9) years vs.(52.9 ±13.1) years) (P=0.01).There were no statistically significant differences between the two groups in body weight, BMI, waist circumference, neck circumference, and bilateral hand grip strength (all P>0.05).According to body compo-sition analysis, the body weight [ (94.8 ±18.3) kg vs.(86.9 ±17.2) kg], body fat mass [ (39.7 ± 11.3) kg vs.(33.5 ±8.9) kg], body fat percentage [ (41.7 ±6.5)%vs.(38.5 ±6.7)%], and visceral fat area [ (145.3 ±24.8) cm2 vs.(130.7 ±27.5) cm2 ] were larger in the non-diabetes group than in the di-abetes group ( all P<0.05) .There were no statistically significant differences between the two groups in BMI and skeletal muscle mass (both P>0.05).Conclusion Compared with diabetes patients, overweight and obese non-diabetes patients may be younger, having worse dietary habits, and having larger body fat mass, body fat percentage, and visceral fat area.

ObjectiveTo explore sensitivities and specificities of Nutritional Risk Screening 2002 ( NRS 2002),Subjective Global Assessment (SGA),and Mini Nutritional Assessment (MNA) in the detection of blood prealbumin level.MethodsTotal 126 patients were consecutively enrolled from the oncology departments of three hospitals from November,2010 to March,2011.Nutritional screenings or assessments were performed on the next morning of hospital admission by nutritionists and medical oncologists using NRS 2002,SGA,and MNA.Prealbumin ( ＜ 180 g/L) was used as the reference standard of malnutrition (undernutrition) for assessing the sensitivities/specificities of these tools.ResultsAll 126 patients completed nutritional screening or assessment using the above three tools.The prevalence of malnutrition (undernutrition) determined by NRS 2002,SGA and MNA was 67.0％,46.2％,and 64.8％,respectively.With prealbumin in relation to clinical outcome as the reference standard,the sensitivities ofNRS 2002,SGA,and MNA were 78.2％,58.2％ and 89.1％,and the specificities were 50.0％,72.2％,and 27.8％,respectively.ConclusionsAmong these three tolls,NRS 2002 detects the nutrition risks,whereas SGA and MNA detect malnutrition.Since prealbumin is not an appropriate reference standard,it can not be used for the comparison among the three tools.Nevertheless,NRS 2002 reflects the clinical outcomes,and therefore is suitable for inpatients.

Objective To clarify the role of MafA gene in development of MODY (maturity onset diabetes of the young) by studying insulin production,gene expression,and serum glucose level in heterozygous MafA gene knockout mice.Methods C57BL/6J mice were used as control animals,MafA gene heterozygous mice were analyzed.The distribution curve of blood sugar levels over time and serum insulin of heterozygous mice were determined by using IPGTT.The sensitivity of the mice to insulin was examined by injecting insulin assay.The expression levels of genes of MafA,insulin,pdX1,Beta2,and other genes of heterozygous mice were analyzed by semi-quantitative RT-PCR.Morphological changes in pancreatic tissue and α-and β-cell counts were obtained by using immunofluorescence/histological examination.Results (1) Two weeks after birth,MafA gene heterozygous mice began to show that the blood glucose level was increased,weight was reduced,and the amount of insulin secretion was clearly decreased (P＜0.05 or P＜0.01) while the insulin sensitivity did not change significantly.(2)The islet volume in MafA gene heterozygous mice was increased significantly as compared with the control group.However there were no significant changes in the number of pancreatic cells,distribution patterns,and the ratio of α and β cell.(3) Semi-quantitative RT-PCR detection showed that,compared with the control group,MafA gene level,the amount of insulin and Beta2 gene in MafA gene heterozygous mice were significantly reduced(all P＜0.05),while no changes in the amount of glucagons and level of Pdx1 were found.Conclusions The blood glucose level of MafA gene heterozygous mice was raised early after birth.MafA gene is likely to be a new disease ralated gene of MODY.

Objective To explore the expression of PIWIL1 protein and DICER enzyme in hepa tocellular carcinoma (HCC) and their significance.Methods Immunohistochemical method was used to detect the expression of PIWIL1 and DICER in 47 cases of HCC and the adjacent HCC tissues.Western blot method was used to detect the expression of PIWIL1 and DICER in 31 cases of fresh HCC tissues and their adjacent HCC tissues.The relationship between PIWIL1 and DICER and their relationships were analysed with clinical features.12 cases of normal liver tissues were used as control group.Results The expression of PIWIL1 was high in HCC but low in normal liver tissues (P＜ 0.05).The expression of DICER was high in normal liver tissues but low in HCC (P＜0.05).The expression of PIWIL1 was positively correlated with invasion to adjacent tissues and histological differentiation (P＜0.05).The expression of DICER was negatively correlated with invasion to the adjacent tissues and histological differentiation (P＜0.05).There was a negative correlation between PIWIL1 and DICER (P＜ 0.05).Conclusions High expression of PIWIL1 and low/missing expression of DICER was related to pathological differentiation and invasion of adjacent tissues.

Objective To compare the efficacy and safety of transurethral plasmakinetic resection of prostate (PKRP) and transurethral resection of prostate (TURP) for benign prostatic hyperplasia (BPH). Methods The clinical and follow-up data of 186 patients with BPH were analyzed retrospectively. Two groups of BPH patients (90 patients in PKRP group,96 patients in TURP group) were treated by PKRP and TURP,respectively. The clinical date and therapeutic result were measured and compared for both in-tra-and inter-groups. Results In PKRP group,the operative time,intraoperative bleeding,the rates of damage of prostate surgical membranes,secondary hemorrhage (within 1 month),the rates of postoperative temporary urinary incontinence (within 2 months) were (65.3 ± 12.8)min,(213.6 ± 78.2)ml,5.6%(5/90),2.2% (2/90)and 21.1% (19/90),respectively,while in TURP group,these parameters were (83.6 ± 17.5) min,( 397.4 ± 142.7 )ml,17.7%( 17/96 ),11.5% ( 11/96 )and 36.5% ( 35/96 ),respectively. There were signif-icant differences between the 2 groups (P < 0.05 ). In PKRP group,the international prostate symptom score (IPSS),quality of life(QOL),Qmax and PVR were (4.7 ± 1.3 )scores,(1.1 ± 0.4)scores,( 18.7 ± 5.6)ml/s,(8.9 ± 2.5)ml,respectively,while in TURP group,these parameters were (5.3 ± 1.0)scores,(1.2 ± 0.5) scores,(20.4 ± 4.3 )ml/s,(11.2 ± 3.2)ml,respehively. These parameters were significantly improved after both procedures(P < 0.05),but there was no significant difference in the above parameters between the 2 groups (P > 0.05). Conclusions PKRP and TURP have similar efficacy in the treatment of BPH,but PKRP ap-pears to have an advantage of more safety and easier blood controls with less physical damage and complica-lion than those in TURP. PKRP is a better treatment option for BPH.