Objective To explore the metabolic phenotype of the adult offspring rats with maternal severe hyperglycemia during pregnancy and overfeeding in early life. Methods The adult Wistar rats were administered intraperitoneally with 20% Streptozotocin (STZ, 50 mg/kg) on day 5 of pregnancy to induce severely gestational diabetes mellitus (SDM) model (blood glucose ≥20 mmol/L). Early postnatal overfeeding models were established through reduction of the number of newborn rats fed by one mother rat. Offsprings were divided into 3 groups according to maternal blood glucose level during the pregnancy and feeding patterns during the lactation period (1) control pups (CP) :maternal euglycemia was achieved during pregnancy and eight pups fed by one mother rat; (2)SDM-normal feeding group: SDM mothers and 8 pups fed by one mother rat;(3)SDM-overfeeding group:SDM mother and 4 pups fed by one mother rat. All pups were fed by standard laboratory chow adlibitum after weaning at 3 weeks of age. The body weight of all pups were measured weekly after weaning. At the age of 26 weeks, the systolic blood pressure (SBP), diastolic blood pressure (DBP) ,heart rate (HR) and metabolic markers, including fasting plasma glucose (FPG), fasting insulin (FINS), total triglyceride (TG), total cholesterol (TC), low density lipoprotein-cholestrol (LDL-C)and high density lipoprotein-cholestrol (HDL-C) were measured in all 3 groups. ANOVA and LSD test were applied in statistical analysis. Results The average plasma glucose level was significantly higher in the SDM mothers than in the controls [(28.34±5.14) mmol/L va (6.25±1.41) mmol/L,P＜0.05]. After weaning at 3 weeks, the weight of SDM-overfeeding group and SDM-normal feeding group was lighter than that of CP group [(43.63±4.83) g, (31.45±10.21) g vs (55.75±8.41) g,P＜0. 05], meanwhile, that of the SDM-overfeeding group were heavier than that of the SDM-normal feeding group (P＜0. 05). Pups in SDM-overfeeding group exhibited catch-up growth during the lactation period, and those in SDM-normal group showed catch-up growth at both lactation period and childhood. At 26 weeks of age, the systolic blood pressure and TG level of pups in SDM-normal feeding and overfeeding group were (153.31 ± 13.91) mm Hg and (147.21 ± 12.29) mm Hg, and (0. 73±0. 22) mmol/L and (0. 71±0.49) mmol/L, respectively, which were higher than those of the CP group [( 132.21 ± 11.26) mm Hg, and (0. 37 ± 0. 08) mmol/L, P＜0.05], but no significant difference was found between the two SDM groups (P＞0.05). There was no difference in FPG levels among the three groups, but the FINS level and HOMA-IR in the SDM-overfeeding group were higher than in the SDM normal feeding and CP group [( 12. 552 ± 3.260) mU/L vs (9.067 ± 1.782) mU/L and (8.590± 0.806) mU/L, 2.400± 0.624 vs 1.797 ± 0.508 and 1.729 ± 0.246; P＜0.05].Conclusions Fetal exposure to maternal severe hyperglycemia during pregnancy may lead to low birth weight infant who will exhibit postnatal catch-up growth. This may lead to the increased risk of metabolic syndrome in the offspings when they grow up, and this process would be accelerated by early overfeeding.

Objective Study the effects of early overfeeding in the adult offspring of mother with severely hyperglycaemia in pregnancy to islet development and insulin resistance. Methods Thirty healthy female Wistar rats were mated with 10 male Wistar rats and the morning on which sperm were found in three different visual fields of the vaginal smear was designated pregnancy day 1. The pregnant rats were intraperitoneally administered with Streptozotocin (STZ, 50 mg/L) on 5th day of pregnancy, and blood glucose exceeded 20 mmol/L to induce severely gestational diabetes mellitus (SDM) model. The pregnant Wistar rats were assigned to two experimental groups: SDM (n = 16) and control (n = 8). Litter size reduction in the lactation period induced early postnatal overfeeding model. Offspring were divided into three groups according to the level of blood glucose in pregnancy and feeding patterns in lactation: ( 1 ) control group (CG):euglycemia in pregnancy, eight pups in lactation;(2) severely gestational diabetes mellitusnormal feeding (SDM-N):severely gestational diabetes mellitus, eight pups in lactation; (3) severely gestational diabetes mellitus-overfeeding (SDM-O): severely gestational diabetes mellitus, four pups lactation. At the end of the lactation period, all pups were fed standard laboratory chow adlibitum until the date of the experiments. Offspring body weight was measured weekly after ablactation. Serum insulin was measured by enzyme-linked immunosorbent assay (ELISA) and pancreatic islet morphology was analyzed by immunohistochemistry (IHC) in all three groups at 26 weeks of age. Results (1) Blood glucose of pregnant Wistar rats: SDM (28.3 ±5.1 ) mmol/L was statistically higher than control (6.3 ± 1.4) mmol/L ( P ＜ 0.05 ). (2) Growth rates of body weight in 3 - 7 weeks and 3 - 9 weeks: SDM-N: (4. 6 ± 1.3) % and (6.8±2.5)%, SDM-O:(3.2±0.7)% and(4.6±1.2)%,CG:(2.9 ±0.6)% and(4.1 ±0.8)%.The growth rates of body weight in SDM-N and SDM-O were both significantly higher than those in CG ( P ＜0.05 ). (3) Body weight at 26 weeks: CG: (486 ± 132) g, SDM-N: ( 387 ± 115 ) g, SDM-O: ( 382 ± 122) g.There was no statistical difference among the three groups (P ＞0.05). (4) Fasting plasma glucose ( FPG),fasting insulin (FINS), homeostasis model of insulin resistance (HOMA-IR) and insulin sensitivity index (ISI): at 26 weeks, the SDM-offspring has nomal FPG, but more insulin was needed to keep it normal. The insulin level of SDM-O[ ( 12.6 ± 3.3) mU/L ] was statistically higher than those of SDM-N [ ( 10.9 ± 3.3 )mU/L] and CG [ ( 8.6 ± 0.8 ) mU/L ] ( P ＜ 0.05 ). The ISI of SDM-O ( 0.020 ± 0.006 ) was significantly smaller than its HOMA-IR(2.40 ±0.62,P ＜0.05). (5)The morphological change of pancreatic islet: The islets of CG and SDM-N were round or ellipse and have clear boundary between endocrine and exocrine parts and the β cells distributed equally. However, SDM-O islets were not of uniform size and most of islets were hyperplasia and hypertrophy. (6) Relative β cell area of pancreas, β-cell area and islet size: SDM-O:(1.81 ±0.31)%, (57.1 ±3.2)% and(39 067 ±3308)μm2; SDM-N:(1.34 ±0.43)%,(60.9 ±0.6)% and ( 30 570 ± 4824 ) μm2; CG: ( 1.11 ± 0.26 )%, ( 63.7 ± 2.7 )% and ( 26 443 ± 4431 ) μm2.SDM-O has significantly increasing β-cell mass, hypertrophic islet size and slightly decreasing β-cell percentage compared with other two groups (P ＜ 0.05 ). Conclusions The exposure of severely hyperglycemia in pregnancy induces low weight infant and postnatal catch-up growth leading to the possibility of insulin resislance (IR) in adult and early postnatal overfeeding will accelerate such course. Islet morphology of SDM-N has no significant change, indicating that maternal diabetes mainly affected β-cell function but not islet morphological features. SDM overfeeding results in early impairment of islet morphology and function, indicating that the compensation ability of islets has already been impaired and the risk of further development of impaired glucose tolerance (IGT) and diabetes. In conclusion, the nutritonal environment in early life ( duration of pregnancy and lactation) participate in the metabolic programming in adulthood.

ObjectiveTo investigate the effects of Angelica sinensis on the expression of vascular endothelial growth factor (VEGF) Flt-1, Flk-1 mRNA after the brain ischemia-reperfusion injury in rats.MethodsWistar rats were randomly divided into the group A, group B and normal control group. The group A underwent middle cerebral artery occlusion (MCAO) for 2h by suture, group B underwent MCAO for 2h meanwhile received treatment with Angelica sinensis (5 g/kg). Immunohistochemistry and quantitative reverse transcription and polymerase chain reaction (RT-PCR) technique were used to examine the gene expression of VEGF.ResultsThe result of immunohistry revealed that VEGF in the group A and group B reached its peak at 24 h after reperfusion then declined gradually. The result of RT-PCR manifested that the gene expression of VEGF in the group A increased from 3 h after reperfusion and reached its peak at 6 h; in the group B reached its peak on the 3rd day. The expression of VEGF in the group B was significantly increased than group A at the same time point.ConclusionAngelica sinensis can enhance the expression of Flt-1, Flk-1 after transient interruption of cerebral blood flow in rats.

AIM: The present study was undertaken to investigate the effect of angiotensin II (AngⅡ) on expression of MMP-9 in THP-1 macrophages. METHODS: Macrophages converted from THP-1 monocytes by incubating with PMA (0.1 μmol/L) for 48 h were divided into PMA group; PMA+AngⅡ group (10-7mol/L, 1 h); PMA+AngⅡ+PDTC group (10 μmol/L, 30 min) and PDTC group. Western blotting was used to detect the MMP-9 and phosphorylation of NF-κB p65, and the expression of MMP-9 mRNA in THP-1 macrophages was measured by RT-PCR.RESULTS: Compared to control group, the expression of MMP-9 (1.06±0.11, P<0.05) and phosphorylation of NF-κB p65 (1.02±0.10, P<0.05) in THP-1 macrophages were expressed when treated with AngⅡ (10-7mol/L); and the expression of MMP-9 mRNA were upregulated (1.22±0.08, P<0.05). However, NF-κB inhibitor PDTC reduced the NF-κB p65 (0.99±0.12, P<0.01) and MMP-9 (1.04±0.14, P<0.01) expressions and decreased the expression of MMP-9 mRNA (0.90±0.06,P<0.01). CONCLUSION: NF-κB signaling pathway contributes to the expression of MMP-9 in THP-1 macrophage induced by AngⅡ.

Objective To investigate the relationship between cognitive impairment and the other clinical features of subcortical damage in patients with magnetic resonance imaging(MRI)-defined subcortical ischemic vascular disease(SIVD).Methods The cohort for this study included 110 SIVD patients who were divided into 3 groups according to cognitive status:patients with noncognition impairment(SIVD-NCI group,n=34),patients with mild cognitive impairment(SIVD-MCI group,n =47) and patients with vascular dementia (SIVD-VaD group,n =29).The cognitive functions were evaluated by the mini-mental state examination (MMSE) and Montreal cognitive assessment(MoCA),the Cambridge cognitive examination-Chinese version(CAMCOG-C),activity of daily living scale(ADL) and clock drawing task(CDT),etc.Depression symptoms were assessed by the geriatric depression scale (GDS),while the other clinical features of subcortical damage were assessed by the timedGet-Up and Go test,etc.Results There were statistically significant differences in the MMSE,MoCA,CAMCOG-C,CDT and ADL scores among the three groups(H=85.36,F=50.32,55.03,H=27.39,40.87,respectively,all P＜0.05).Gait disturbance,urinary disorder,pseudobulbar palsy,depression and falls were statistically significantly different among the threegroups(x2=21.69,21.41,25.51,6.91,21.87,all P＜0.05).In addition,gait disturbance was increasingly aggravated with the severity of cognitive impairment.In SIVD-MCI group,urinary disorder,pseudobulbar palsy and falls were significantly increased as compared with SIVD-NCI group (x2 =15.57,16.31,8.92,both P＜0.017).Depression was statistically significant different between SIVD-NCIandSIVD-VaD group(x2 =6.90,P＜0.017).Among the three groups,there was no significant difference in the feature of emotional incontinence.Conclusions With the decline in cognitive function,the patients with SIVD can present with different clinical features of subcortical damage.Gait disturbance is gradually aggravated with the decline in cognitive function.Urinary disorder,pseudobulbar palsy,and falls can reflect the cognitive impairment from normal to mild on the other hand.Depression can be used as one of the signs that show cognitive impairment reached to dementia.

ObjectiveTo explore the changes of the levels of cytokines in patients with first-episode depression and the effect on the levels of cytokines after the treatment with duloxetine.MethodsThe serum levels of interleukin 1 ( IL-1 ),interleukin 6 ( IL-6 ),tumor necrosis factor-alpha ( TNF-αt ),interleukin4 ( IL-4 ),interleukin10(IL-10) were measured in 38 patients with depression before and after duloxetine treatment by enzyme linked immunosorbent assay(ELISA).HAMD score were assessed at pre- treatment and post-treatment to assess curative effect.The control group was 30 healthy individuals.All data were statisticaly analyzed by SPSS.ResultsBefore treatment,the HAMD score and the levels of serum IL-6,TNF-α,IL-1 in first-episode depressant patients were remarkablely higher than those in the control group( IL-6:( 10.66 ± 3.12 ) pg/ml vs (2.72 ± 0.91 ) pg/ml ;TNF-α:(77.49 ±3.12) pg/ml vs (37.48 ±5.87) pg/ml; IL-1:(39.09 ± 3.77 ) pg/ml vs ( 10.31 ± 1.05 ) pg/ml ),the levels of serum IL-4 and IL-10 in first-episode depressant patients were remarkablely lower than those in the control group(P＜0.05,P＜0.01 ).The HAMD score and the levels of serum IL-6,TNF-α,IL-1 in post-treatment were remarkablely lower than pre-treatment (P ＜ 0.05 ),but which were still higher than the control group(P＜ 0.05 ).The levels of serum IL-4 and IL-10 in post-treatment were remarkablely increased than pre-treatment(P＜0.05).The levels of serum IL-6,TNF-α,IL-1 were positively correlated with the HAMD score( r =0.667,0.486,0.727,P ＜0.01 ),but the levels of serum IL-4 and IL-10 were negatively correlated with the HAMD scorae ( r=-0.433,-0.269,P＜0.05,P＜ 0.01 ).ConclusionsThe first-episode depressant patients show immune disorder induced by cytokines.Anti-depressant activity of duloxetine may participate in the regulation of cytokines and Th1/Th2 unbalance.

Objective To explore the relationship of cognitive impairment and depression in subcortical ischemic vascular disease (SIVD).Methods Neuropsychological scales were used to investigate the level of cognitive impairment and depression syndrome.According to the diagnostic criteria,the participants were divided into three groups:non-cognitive impairment group (SIVD-NCI),mild cognitive impairment group (SIVD-MCI),and dement group (SIVD-D).Depending on the clinical syndrome and the Geriatric Depression Scale (GDS),the participants were divided into depression group and non-depression group.The interaction of cognitive impairment and depression was analyzed using Analysis of Covariance (ANCOVA).Results The main effect of cognitive impairment was significant in all the Cambridge Cognitive Examination-Chinese version (CAMCOG-C) subscales,while the major function of depression in most of the CAMCOG-C subscales.The interaction of cognitive impairment and depression was significant only in executive function (F =6.835,P =0.001),attention (F =3.126,P =0.047),language (F =3.352,P =0.038) and comprehension of language (F =5.324,P =0.006).The interaction of cognitive impairment and depression was significant in executive function(F =14.255,P =0.000) and comprehension of language (F =3.971,P =0.049) between SIVD-NCI group and SIVD-MCI group while in attention (F =4.918,P =0.030) between SIVD-MCI group and SIVD-D group.Conclusions Patients of SIVD have varying degrees of cognitive impairment and depressive symptoms.Those with depression symptoms have more cognitive impairment than non-depressed patients.Cognitive impairment and depression show interaction in different subscales of cognitive function in different time.

Objective To study the expression of vascular endothelial growth factor (VEGF) and its receptors(VEGFR) mRNA at different time points after focal cerebral ischemic-reperfusion(CIR) in rats. Methods Following the establishment of the of transient ischemia modelof middle cerebral artery in rats by Zea-Longa′s method, the expression of VEGF and its receptors mRNA was measured with semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) at different time points. Results The expression of VEGF mRNA increased 3 h after CIR,and peaked at 6 h, and then declined, returned to the baseline at 7 d. The expression of Flt-1 and Flk-1 mRNA was enhanced at 3 h, and reached its peak at 3 d, then declined gradually. Conclusion The expression of VEGF、Flt-1 and Flk-1 mRNA can be induced by focal CIR in rats.

OBJECTIVE:To study the pharmacokinetics of escitalopram oxalate tablets in human body.METHODS:Es-citalopram oxalate tablets were administered orally at a single dose of30mg to10healthy subjects respectively,the plasma concentration of escitalopram oxalate was determined by HPLC method,the pharmacokinetic parameter was fitted with3p97software.RESULTS:The concentration-time curve of escitalopram oxalate tablets was in line with the two-compartment model,the main pharmacokinetics parameters of escitalopram oxalate were as follows,the C max was(42.73?10.19)?g?L,t max was(2.90?0.32)h,t 1/2 was(35.34?7.78)h,AUC 0～132 was(1241.5?194.3)(?g?h)/L and the AUC 0～∞ was(1327.5?210.5)(?g?h)/L.CONCLUSION:The study on pharmacokinetics can be used as a reference in the clinical medication.

AIM:The present study was undertaken to investigate the effect of angiotensin II (AngⅡ) on expression of MMP-9 in THP-1 macrophages. METHODS:Macrophages converted from THP-1 monocytes by incubating with PMA (0.1 ?mol/L) for 48 h were divided into PMA group; PMA+AngⅡ group (10-7mol/L,1 h); PMA+AngⅡ+PDTC group (10 ?mol/L,30 min) and PDTC group. Western blotting was used to detect the MMP-9 and phosphorylation of NF-?B p65,and the expression of MMP-9 mRNA in THP-1 macrophages was measured by RT-PCR.RESULTS:Compared to control group,the expression of MMP-9 (1.06?0.11,P