Human health and public safety are being threatened while chemicals bring convenience and comfortable to our life. How to reduce and avoid the hazard of chemicals via toxicity warning is becoming more and more important. Today it is necessary to estimate new chemicals conveniently, quickly and precisely. The warning model of chemicals in toxicology has a favorable prospect of application. The toxic effect and kinds of models of chemicals and the study of quantitative structure activity relationships (QSAR) in toxicity research were reviewed in this paper.

Objective To investigate the major risk factors of posterior circulation infarction.Methods Clinical data from 216 patients with posterior circulation infarction were analyzed retrospectively. The patients were divided into follow groups (proxima1,middle, dista1 and combination group,or single , multiple, or unilateral, bilateral, or lacune infarct, non lacune infarct ) according to the infarcts locations on MRI.The risk factors in each group were analysed. Also,the major risk factors were compared with that from patients with anterior circulation infarction. Results In 216 patients with posterior circulation infarction, hypertension was the most common risk factor (76.9%), followed by diabetes mellitus (36.6% ),hyperlipedemia (30.1%), previous stroke history(26%), and heart disease(22.2%). The most common location of infarcts was distal territory (49%),followed by middle(24.5%) ,proxima1(6%). The average age of proximal group [(57.92?12.81) years] was significant lower than that of other groups(P

ObjectiveTo investigate the effects of the asphyxia as a Second Hit on renal function during early stage after birth in small for gestational age (SGA) infants.MethodsThe infants who were hospitalized within 24 hours after birth in Peking University Third Hospital between January 2013 and March 2015 were retrospectively enrolled, and divided into different groups depending on gestational age and asphyxia history. There were 40 preterm non-asphyxia SGA infants and 80 controls who were preterm non-asphyxia appropriate for gestational age (AGA) infants; 11 preterm asphyxia SGA infants and an equal number of preterm asphyxia AGA infants as controls; 33 term non-asphyxia SGA infants and 33 term non-asphyxia AGA infants as controls; and four term asphyxia SGA infants and 13 term asphyxia AGA infants as controls. Blood urea nitrogen (BUN), serum creatinine (SCr), and estimate glomerular filtration rate (eGFR) were tested within 48 h after admission and the incidence of abnormal indexes was compared between groups byt-test and Fisher exact test.Results(1) Compared with preterm non-asphyxia AGA group, BUN level significantly decreased in preterm non-asphyxia SGA group [(3.99±1.69) vs (5.11±2.08) mmol/L,t=2.948, P=0.004]. Compared with term non-asphyxia AGA group, term non-asphyxia SGA group had higher SCr level [(72.03±10.29) vs (62.58±12.27)μmol/L,t=3.390,P=0.001] and lower eGFR level [(25.19±4.07) vs (33.99±8.75) ml/(min·1.73 m2),t=5.238,P=0.000]. (2) Compared with preterm non-asphyxia AGA infants, preterm asphyxia AGA infants had higher BUN [(6.96±3.09) vs (5.11±2.08) mmol/L,t=2.602,P=0.011] and SCr [(76.45±10.11) vs (66.70±13.18)μmol/L,t=2.357,P=0.021] and lower eGFR level [(15.86±2.31) vs (19.54±5.08) ml/(min·1.73 m2),t=2.361,P=0.020]. Compared with preterm non-asphyxia SGA group, there was a significant increase in BUN level [(6.70±3.37) vs (3.99±1.69) mmol/L,t=2.581,P=0.025] and decrease in eGFR level [(14.80±4.67) vs (18.66±5.03) ml/(min·1.73 m2),t=2.285,P=0.027] in preterm asphyxia SGA group. Changes in term infants were similar to preterm infants. (3) Compared with asphyxia AGA group, asphyxia SGA group showed a higher frequency of abnormal eGFR in term infants (4/4 vs 4/13, Fisher exact test,P=0.029). ConclusionsAsphyxia as a probable Second Hit can influence the renal function during early stage in both preterm and term infants, especially in SGA infants.

Cardiovascular System ; Forkhead Transcription Factors ; Humans

AIM:To detect the changes of cystathionine β-synthase (CBS) expression in the brain following ischemia-reperfusion of hind limbs in the rats and to elucidate their significance .METHODS:Hind limb ischemia was in-duced by clamping infrarenal aorta with a microvascular clip and brain injury was made by following reperfusion .The brain tissue was obtained from the animals subjected to sham operation , 4 h of ischemia without reperfusion and 3 h, 6 h, 12 h, 24 h of reperfusion following 4 h of ischemia .The expression of CBS at mRNA and protein levels was measured at different time points by reverse transcription-polymerase chain reaction ( RT-PCR) and Western blotting .The CBS activity and hy-drogen sulfide ( H2 S) concentration in the brain were determined by a universal microplate reader .The observation of path-ologic changes of the brain was made following the inhibition of CBS by hydroxylamine .RESULTS:The relative expression of CBS at mRNA and protein levels in IR group significantly increased compared with sham group .It reached a peak at 12 h (P<0.01), and returned to baseline at 24 h (P>0.05).This time course correlated with increased CBS activity and H2 S concentration .No statistically significant difference in the above indexes between sham operation group and ischemia group was observed (P>0.05).Inhibition of CBS activity induced more severe brain injury in IR group .CONCLUSION:Up-regulation of CBS/H2 S pathway is involved in the protection for neurons during the ischemia-reperfusion of hind limbs .

BACKGROUND:Animal experiments have repeatedly verified that umbilical cord stem celltransplantation can improve the rotational behavior of rats with Parkinson’s disease, with lower immune rejection response.
OBJECTIVE:To evaluate the therapeutic effects of human umbilical cord mesenchymal stem celltransplantation in the treatment of Parkinson’s disease using the Unified Parkinson’s Disease Rating Scale.
METHODS:Fifteen patients with Parkinson’s disease were enrol ed, including 8 males and 7 females, aged 52-76 years. Hoehn&Yahr staging was 3-5. After informed consent was obtained from puerperae and the procedure was approved by the hospital ethics committee, ful-term maternal umbilical cord was aseptical y col ected, to culture umbilical cord mesenchymal stem cells. Al patients were hospitalized, and treated with human umbilical cord mesenchymal stem celltransplantation via carotid artery puncture. Neurological function of patients was assessed using a comprehensive rating scale for Parkinson’s disease before and 1 month after cells transplantation. Higher score indicated more severe neurological deficits.
RESULTS AND CONCLUSION:Fifteen patients entered the result analysis. Compared with before transplantation, 15 patients showed significantly lowered scores on the Unified Parkinson’s Disease Rating Scale at 1 month after transplantation (P<0.05). The improvement was mainly concentrated in the tremor and rigidity, but bradykinesia and unstable position were not improved. Graft versus host disease did not occur in al 15 cases. These findings indicate that umbilical cord blood mesenchymal stem celltransplantation for treating Parkinson’s disease has obvious curative effects and significantly improves neurological functions.

Objective:To explore the hepatocyte insulin sensitivity of intrauterine growth retardation ( IUGR) rats and establish an insulin resistance cell model in vitro.Methods: An IUGR animal model was established by protein malnutrition during the mother pregnancy .On 60 d and 90 d after birth , the offspring rats were fasted for 12 hours and then their angular vein blood was collected to measure the fasting plasma glucose and fasting serum insulin level , then the insulin resistance index ( HOMA-IR) and insulin sensitivity index ( ISI) were calculated .The insulin sensitivity was evaluated by HOMA-IR and ISI.Primary hepatocytes from each group were respectively isolated by two-step perfusion with collage-nase and were defined as normal hepatocytes group and IUGR hepatocytes group .The normal hepatocyte group was divided into two groups: control group and insulin induction group .Insulin induction group was established by primary cultures of normal hepatocyte incubated with varying dilutions of insulin . CCK-8 was used to detect the viability of the cultured hepatocytes .Glucose oxidase-peroxidase method kit was used to measure glucose consumption of the hepatocytes .Results:HOMA-IR was significantly higher in IUGR rats than in the normal rats at the age of 60 days ( t=-17 .02 , P<0 .05 ) and 90 days ( t=-12.52, P<0.05).ISI was significantly lower than in the normal rats aged 60 days (t=5.61, P<0.05) and 90 days (t=12.42, P<0.05).There were no significant differences in hepatocyte viability among the control group , IUGR group and insulin induction group after incubation of 48 h on day 60 (F=1.34, P=0.29) and day 90 (F=0.22, P=0.81).The glucose consumption of the IUGR group and insulin induction group were significantly decreased compared with the control group on day 60 ( F=9.28, P=0.002) and day 90 (F=56.60, P<0.001), while there was no significant difference be-tween the IUGR group and insulin induction group (P=0.08, P=0.10).Conclusion:The insulin sen-sitivity of hepatocytes of IUGR rats decreased from adolescence to adulthood .High-dilution insulin may induce insulin resistance cell model in vitro.

Objective To study the changes of serum CORT,SOD and LPO in large-acreage cerebral insarction(LCI) and hyperthermia patients,and observe the effect of head hypothermia on them.Methods All cases of LCI were divided into head hypothermia treatment group(group A,n=49),warm water bath and glacial saline enema treatment group(group B,n=43),and health group(control group,group C,n=30).With the methods of radioimmunoassay,hydroxylamine oxidation and thirddialdehyde,the serum CORT,SOD and LPO level in the two groups were measured on the 2nd day after hospitalization and on the 2nd day,the 3rd day and the 4th day after hyperthermia.In addition,the life quality scores of the two groups were compared.Results The serum CORT,LPO of group A and group B were higher on the 2nd day after hospitaiization than the group C(P0.05),while the SOD were lower(P

Objective To investigate the effect of liver phosphatidylinosital 3-kinase/protein kinase B (PI3-K/AKT) pathway on the decrease of insulin sensitivity in fetal growth restriction (FGR) rats.Methods Twenty pregnant female rats were randomly divided into two groups one day after conception:normal-protein group and low protein group (n=10,respectively).Rats in low-protein group was given low protein diet (8.00％ protein) during pregnancy to build FGR model,while normal-protein group was given normal protein diet (20.00％ protein).On day 3,7,14,30,60 and 90 after birth,fasting blood samples of 8 male FGR offsprings from low-protein group and 8 normal offsprings from normal-protein group were collected to measure fasting plasma glucose and insulin level.Then insulin resistance index and insulin sensitivity index were calculated to determine insulin sensitivity.On day 7,14,30,60 and 90 after birth,liver tissue of 8 male FGR and normal offsprings were collected,insulin receptor substrate 1,2 (IRS1/IRS2)and glucose transporter 4 (GLUT4) mRNA expression were measured by real-time fluorescence polymerase chain reaction and the protein expressions of IRS1,PI3-K (subunit p110β),and AKT and phosphorylated AKT (pAKT) were measured by Western blot.The relationships between the expression changes of key molecules of PI3-K/AKT pathway and insulin sensitivity were analyzed by correlation and multiple linear regression method.Results (1) Mean birth weight of baby rats in low-protein group was significantly lower than that of normal-protein group [(4.92±0.36) g vs (6.43±0.59) g,t=14.73,P＜0.05].The incidence of FGR in low-protein group was 88.2％ (97/110); and for male offsprings,it was 94.1 ％ (48/51).(2) Compared to normal offsprings,fasting plasma glucose levels of male FGR offsprings were significantly higher from the age of 60 days to 90 days.Insulin levels and insulin resistance index were significantly higher and insulin sensitivity index was lower from the age of 30 days to 90 days,P＜0.05 respectively.(3) Compared to normal offsprings,IRS1 (0.45 ± 0.02 vs 0.68± 0.03,t=16.633,P＜0.05) and IRS2 mRNA (0.34±0.10 vs 0.70±0.19,t=4.864,P＜0.05) expressions in FGR offsprings were lower from day 7 after birth to day 90 (0.48±0.03 vs 0.59±0.05,t=5.237,P＜0.05; 0.49±0.20 vs 0.70±0.11,t=2.253,P＜0.05).There were no differences in expressions of GIUT4 mRNA and AKT protein between two groups (P＞ 0.05).IRS1,PI3-K and pAKT protein expressions of FGR offsprings decreased significantly from day 14 (0.22±0.05 vs 0.52±0.11,t=7.024,P＜0.05; 0.46±0.03 vs 0.97±0.08,t=17.508,P＜0.05; 0.62±0.10 vs 0.89±0.08,t=6.100,P＜0.05) to day 90 (1.11±0.08 vs 1.32±0.14,t=3.714,P＜0.05; 0.63±0.07 vs 1.00±0.19,t=5.206,P＜0.05;0.28±0.03 vs 0.45±0.10,t=4.880,P＜0.05).(4) The pAKT protein expression level of FGR rats was positively correlated with insulin sensitivity index (r=0.704,P＜0.05) ; while negatively correlated to the level of fasting plasma glucose (r=-0.609,P＜0.05),fasting insulin (r=-0.561,P＜0.05) and insulin resistance index (r =0.577,P＜ 0.05).Conclusions The changes of some key molecules' expressions of PI3-K/AKT pathway in liver might be involved in the insulin resistance in FGR rats.

Objective To investigate the effects of resveratrol on cell growth,migration,and invasion of human breast cancer cell line MDAMB-231.Methods MTT assay and soft agar colony formation assay were used to detect the effects of resveratrol on cell growth.The effects of resveratrol on cell migration and invasion were determined by Transwell migration assay and Transwell invasion assay.respectively.Results Resveratrol(25 to 200 μmol/L)inhibited the growth of MDA-MB-231 cells in a time-and concentration-dependent manner(P＜0.01).The colony formation rate of MDA-MB-231 cells decreased with the increase in the concentrations of resveratrol.After being treated with resveratrol of 25,50,100 and 200 μmol/L for 24 hours,the invasive and migratory ability of MDA-MB-231 cells was significantly inhibited (P＜0.01).Conclusion Resveratrol could inhibit the growth of MDA-MB-231 cells,and the invasive and migratory ability of MDA-MB231 cells is also inhibited by resveratrol through degrading extracellular matrix.