Objective To evaluate the repeated dose toxicity of MNT-016 in SD rats and to provide reference for toxicity evaluation.Methods MNT-016 was administered to rats at 5, 20 and 80 mg/kg for 90 days.The toxic effects on the animals were evaluated by observing the clinical signs and measuring the body weight, hematology and blood biochemistry as well as histopathological examination.NOAEL and benchmark dose lower confidence limit(BMDL) were observed by the end point of toxicity.Results Compared with the control group, the AST, TBIL, DBIL and Crea of male rats were increased in a dose-dependent manner, while TG and CHOL decreased.The body mass(before anatomy), heart, liver, thymus, epididymis of male rats in 80 mg/kg group were significantly decreased (P<0.05), while absolute organ mass of the heart and lung was increased.The body mass (before anatomy) and thymus of female rats in 80 mg/kg group were significantly decreased (P<0.05), while absolute organ mass of lungs was increased.Vacuolation of hepatocytes was observed in groups each dose, tubule atrophy was found in the kidneys of 20 and 5 mg/kg groups, and tubule basophilia was observed in 80 mg/kg group.The incidence of the above lesions was higher in male animals than in female ones.Conclusion The NOAEL of MNT-016 is lower than 5 mg/kg in male rats and 5 mg/kg in female rats.BMDL value is 2.65 mg/kg in male animals and more accurate than NOAEL, and is 9.04 mg/kg in female animals,which is slightly larger than the corresponding NOAEL.

OBJECTIVE To study the toxicity of zinc oxide nanoparticles (ZnO-NPs) on murine macrophage Ana-1 cells and the mechanism.METHODS Ana-1 cells were incubated with ZnO-NP (2.5-160 mg· L-1).Cell viability was investigated by MTT assay.The integrity of cell membrane was investigated by acridine orange-ethidium bromide (AO-EB) staining.The intracellular uptake of ZnO-NP and the percentage of sub-G1 of Ana-1 cells were detected by flow cytometry.Zinc ions were determined by fluorescent probe.The change of cell viability was studied after chelating zinc ions with ethylene diamine tetraacetic acid (EDTA).RESULTS ZnO-NP 2.5,5,10 and 20 mg· L-1 decreased cell viability of Ana-1 cells (r=0.905,P＜0.05) in a concentration-dependent manner.The cell viability was decreased to 27.9％ after exposure to ZnO-NP 20 mg· L-1.Intracellular uptake of ZnO-NP was increased after Ana-1 cell incubated with ZnO-NP at concentrations ranging from 40 to 160 mg· L-1 (P＜0.05).There were obvious free zinc ions in the cells.EDTA 2.5 mmol· L-1 significantly increased the cell viability decreased by ZnO-NP 20 mg· L-1 (P＜0.05).Chelating free zinc ions significantly mitigated ZnO-NP induced cell toxicity (P＜0.05).CONCLUSION Cytotoxicity and apoptosis of Ana-1 cells induced by ZnO-NP might be related to intracellular uptake of ZnO-NP and release of zinc ions.

Objective To assess the role of Matrix Metalloproteinase-9 (MMP-9)in rheumatoid arthritis (RA).Methods Peripheral blood from 45 RA patients and 28 healthy individuals (HV)were collected to detect RF and hs-CRP by immuno-turbidimetry,ESR by westergren method and MMP-9 by ELISA.The correlation was analysed between MMP-9 and RF, ESR or hs-CRP,respectively,by pearson correlation analysis.Results Levels of RF,ESR,hs-CRP and MMP-9 were signifi-cantly higher in RA patients than HV group (t=3.93~5.96,P<0.001),respectively.RF high titer patients or patients with a high inflammation response showed a higher MMP-9 levels than the RF low titer or slight inflammation patients (P<0.05).MMP-9 was positively correlated to RF,ESR and hs-CRP in RA patients(P<0.05),respectively.Conclusion MMP-9 maybe a sensitive tool in the diagnosis and management of RA patients.

BACKGROUNDBy synthesizing results from primary studies, systematic review can provide empirical information of concerned problems. This study aimed to review the available surveillance data from studies reporting the contamination surveillance of food lead in China.

METHODSRelevant studies were identified by systematically searching Chinese Biological Medicine Database and China National Knowledge Infrastructure using the key term of "lead" for surveillance data published in Chinese between 2006 and 2012. To avoid potential selection bias, all articles were evaluated by two independent reviewers, and the disagreements were resolved by discussion or the third author was asked to arbitrate.

RESULTSAmong 269 identified publications on surveillance data of lead in food, 43 articles met the defined inclusion criteria. The food samples were divided into 11 groups (cereal grains and pulses, fish, eggs, vegetables, meat, edible fungi, milk and dairy products, fruits, offal, tea and preserved egg). Surveillance data of publications were reviewed to calculate the weighted mean and rate exceeding maximum levels. Our results indicated that the highest lead concentration was 1.937 mg/kg in tea. The total percentage of samples exceeding the maximum levels was 5.57%. Dietary exposure to lead was assessed by combining the weighted mean concentration of surveillance data with national consumption data in 2002. In this review, dietary intake of lead was 1.232 µg/kg b.w./day.

CONCLUSIONFurther control measures should be taken to reduce exposure to lead, from both dietary and non-dietary sources.

Objective To investigate the effect of noninvasive positive pressure ventilation treatment on patients with acute left heart failure and hyoxemia.Methods Sixty-two patients with acute left heart failure and hyoxemia were divided into control group (31 cases) and treatment group (31 cases).All patients were treated with a conventional therapy plan and patients in treatment were received noninvasive positive pressure ventilation beside conventional therapy.Blood gas analysis,plasma B-type natriuretic peptide (BNP) and clinical manifestation before and after treatment were monitored.Results The time of clinical manifestation al0leviation in treatment group was (33.7 ±7.9) min,shorter than that of control group ((55.9 ± 12.1) min,t =8.554,P ＜0.01).Compared with pre-treatment,heart rate (HR),respiratory rate(RR),mean arterial pressure(MAP),pH,oxygen saturation of blood (SaO2),arterial partial pressure of oxygen (PaO2),arterial partial pressure of carbon dioxide(PaCO2) and BNP in treatment group were improved significantly(HR:(133.89 ± 5.45) beat/ min vs.(87.27 ± 5.74) beat/min,t =32.794,P ＜ 0.01 ; RR:(34.25 ± 5.67) beat/min vs.(20.15 ± 2.54) beat/min,t =12.636,P ＜ 0.01 ; MAP:(104.52 ± 7.25) mmHg vs.(76.57 ± 3.76) mmHg,t =19.055,P ＜0.01; pH:(7.29±0.06) vs.(7.40 ±0.06),t=7.218,P＜0.01;SaO2:(81.52 ±5.01)％ vs.(97.16±1.27) ％,t =16.848,P ＜ 0.01 ; PaO2:(55.30 ± 7.14) mmHg vs.(92.80 ± 6.24) mmHg,t =22.019,P ＜0.01;PaCO2:(46.23 ±10.30) mmHg vs.(40.56 ±5.19) mmHg,t =2.737,P＜0.05;BNP:(831.59 ±292.65) ng/L vs.(265.52 ±65.39) ng/L,t =10.511,P ＜0.01).And after treatment,HR,RR,MAP,SaO2,PaO2,BNP in control group were improved compared with that before treatment (HR:(132.13 ± 5.31) beat/min vs.(92.15 ± 4.28) beat/min,t =32.638,P ＜ 0.01 ;RR:(34.96 ± 4.78) beat/min vs.(23.91 ± 3.27) beat/min,t=l0.634,P＜0.01;MAP:(102.56 ±7.14) mmHg vs.(82.83±3.52) mmHg,t =13.800,P＜0.01;SaO2:(82.15 ± 5.24) ％ vs.(93.16 ± 2.59) ％,t =10.488,P ＜ 0.01 ; PaO2:(54.56 ± 6.27) mmHg vs.(75.19 ±3.52) mmHg,t =15.974,P ＜0.01 ;BNP:(823.15 ±277.26) ng/L vs.(371.15 ±87.55) ng/L,t =8.656,P ＜0.01).Statistical differences of pH and PaCO2 were not found in the control group before and after treatment(pH:7.32 ± 0.05,t =1.426,P =0.159 ;PaCO2:(43.78 ± 6.74) mmHg,t =0.253,P =0.801).HR,RR,MAP,pH,SaO2,PaO2,PaCO2 and BNP in treatment group were more significantly improved than that of control group(t =3.795,5.056,6.767,5.703,7.721,13.686,2.107 respectively,P ＜ 0.01or P ＜ 0.05).Conclusion The therapy plan of noninvasive positive pressure ventilation on patients with acute left heart failure and hyoxemia can improve cardiac function and oxygenation quickly,and decrease the plasma BNP level.

Peroxisome proliferator-activated receptors (PPARs)are ligand-activated nuclear tran-scription factors,playing an important role in the regulation of glucose and lipids metabolism,inflamma-tion response,proliferation and differentiation.Some drugs targeted on PPARs,such as lipid-lowering and antidiabetic drugs have been developed.Some PPAR agonists were found carcinogenic in animal experi ments,including PPAR αagonist fibrates,PPARγagonist thiazolidinediones,PPARα/γdual ago-nist compounds,and PPARδagonist compounds for clinical development.PPARαagonist carcinogenicity is associated with PPAR receptor activation that regulates lipid metabolis m,and leads to lipids abnormali-ties and increase by peroxisome oxidase in reactive oxygen species (ROS),causing DNA damage. Kupffer cells can generate ROS by NAD PH oxidase that pro motes hepatocyte proliferation and inhibition of apoptosis.PPARγagonist carcinogenicity is generally caused by bladder stone.The carcinogenicity of PPAR agonists to humans has not been confirmed,but the carcinogenic potential of these drugs can-not be ignored.

This study is to establish a simple and practical co-culture method of cortical neurons and astrocytes of rats. The cortex of the new-born SD rats was digested by 0.125% pancreatic enzyme, and the differential adherence was applied to obtain the mixed cell suspension of neurons and astrocytes. A low concentration of cytarabine was used to inhibit the astrocytes in a moderate way to get neuronal and astrocyte co-culture. The morphological characteristics of the cells in different times were observed under the inverted microscope. The cells began to adhere the wall 2 h after the inoculation. Neurons and astrocytes grew in a good condition under the inverted microscope 9 days after the inoculation. The results of the immunofluorescence staining and Rosenfeld's staining indicated that the co-culture of neurons and astrocytes was successful and the ratio of neurons and astrocytes was close to 1:1. A new neurons and astrocytes co-culture method, which is simple and convenient, was successfully established. It will be an efficient method for the related researches about neuronal and astrocyte co-culture in vitro.

Objective:Clonidine,by activating peripheral α-sbrenoceptors, produces transient pressor response after i.v.injection in anesthetized animals.Moxonidine, with at least 40-fold higher affinity to I1-imidazoline receptors than to α2-adrenoceptors,produces also a transient pressor response. This work was designed to investigate whether I1-imidazoline receptors are involved in this pressor effect of moxonidine. Methods:Female spontaneously hypertensive rats(SHRs,aged 14-16 weeks)were anesthetized with urethane.To observe the transient pressor responses,moxonidine 0.1,0.3,1.0mg/kg(intravenous,i.v),2.0μg(intracerebroventricular,i.c.v.)and 1.0,10.0mg/kg(intragastric,i.g.)were administrated in different groups of rats.To evaluate the roles of α1-adrenoceptors,α2-adrenoceptors and I1-imidazoline receptors in the transient pressor responses to moxonidine, prazosin(10.0μg/kg),yohimbine(2.0mg/kg),phentolamine(0.2mg/kg),idazoxan(1.0mg/kg)or yohimbine+idazoxan(2.0mg/kg+1.0mg/kg)were intravenously given to the animals before moxonidine 0.3mg/kg (i.v.).Results:It was found that i.v.moxonidine produced a greater pressor response than clonidine when producing a similar reduction of blood pressure.This effect of moxonidine was not influenced by prazosin, but was partly inhibited by yohimbine, phentolamine or idazoxan,and completely blocked by the combination of yohimbine and idzaxon.Neither i.c.v.injection nor i.g. administration of moxonidine induced transient pressor responses.Conclusion:The transient pressor response of i.v. moxonidine is mediated by both peripheral I1-imidazoline receptors and α2-adrenoceptors.

PPAR ? is one of the three isoforms of peroxisome proliferator-activated receptors (PPARs) which are essential regulators of lipid storage and metabolism. PPAR ? primarily stimulats lipid metabolism and energy uncoupling in adipocytes and myocytes as well as involvs in the onset and development of many diseases. As the target of medicines, PPAR ? agonists may be powerful drugs for epidermal wound and metabolic syndrome X.