Objective:To study the effect of B7-1 costimulatory molecule in inducing tumor immunity.Methods:The lymphocytes were examined in vitro,for both proliferation induces(PI) and specific cytotoxic activity,H22 mice were challenged subcutaneously either by the mock following which the latency,survival time and tumor mass growth were noted.Results:The H22-B7-1 cells more effectively induced the proliferation of effecter lymphocytes and the generation of specific lytic activity against H22 cells.The H22-B7-1 cells demonstrated slower rate(P

Objective To exam the exposure status to tobacco advertisement and promotion programs in Chinese middle school students.Methods Stratified multi-stage cluster sampling was used to select participated grade 7-9 middle school students in 31 provinces (n=155 117).A self-administrated questionnaire was used in which questions related to behavior on tobacco use,exposure to second-hand smoking (SHS),access to tobacco products and prices,tobacco control advocacy,exposure to tobacco advertisement,and promotion as well as attitude and knowledge towards tobacco,etc.Data was weighted and analyzed,using the complex survey module of SAS 9.3 software.Results In the past 30 days,48.5％ of the students had a chance to see advertisement or promotion programs on tobacco.Tobacco advertisement or promotion were most frequently seen on TV (21.3 ％) among students,followed by outdoor billboard (20.1％),at the stands for sale (17.5％),and Internet (15.6％).In addition,4.6％ of the students reported having kept the items related to brand logos of tobacco products; 2.0％ reported having been offered a free tobacco product by tobacco company representatives; 69.7％ reported having seen scenes related to smoking on TV/videos/movie screens.Twenty five point two percent of the student smokers reported buying individual sticks at last purchase.Among those students who had never been exposed to tobacco,the ones who had been exposed to tobacco advertisement and promotion programs reported that they were more likely to feel smoking attractive than those who had not.They also reported that if a cigarette was offered by friends,they might try to smoke within the next 12 months,feeling that smoking would make him/her comfortable,and finally to feel that they might enjoy smoking (P＜0.000 1).Conclusion Adolescents had been heavily exposed to tobacco advertisement and promotion programs in China.Students who had been exposed to tobacco advertisement or promotions were more likely to express positive attitude to tobacco use.It is urgent to make amendments to China's Advertising Law to completely prohibit tobacco advertisement,promotion and sponsorship programs,to keep the young people away from tobacco.

Objective:To explore the safety and efficacy of immune checkpoint inhibitors(ICI)for patients with tumor recurrence after liver transplantation(LT).Methods:A single-center retrospective study was conducted for 6 recipients of tumor recurrence after LT on a therapy of ICI admitted into Shulan(Hang Zhou)Hospital from September 2015 to June 2018.The authors examined the occurrences of graft rejection and clinical outcomes of overall response rate, progression-free survival and overall survival after dosing of PD-1/PD-L1 inhibitors.Results:Six patients enrolled with tumor recurrence on a therapy of ICI undergoing LT due to hepatocellular carcinoma (HCC). Nivolumab (n=4) and duvalizumab (n=2) were administrated.The median session of treatment was 8.3(2-31) cycles.The disease outcomes were stable (3/6, 50%) and progressive (3/6, 50%), The progression-free survival time of 3 disease-controlled patients was 1.5, 16.2 and 18 months and the median survival time after recurrence was 19.75(10.8-37.8) months.Rejection occurred in 1 patients (1/6, 16.7%) and the occurring time of rejection was 28 days after PD-1 inhibitor dosing.After acute rejection, high-dose corticosteroids and immunoglobulin were ineffective and the patient died from acute rejection related liver failure.Conclusions:ICI may be employed as a salvage treatment for tumor recurrence after LT for HCC.Due to a possibility of severe acute rejection, usage should be cautious under close monitoring of liver function.

OBJECTIVE：To investigate the effects of Buyang huanwu decoction on lipid metabolism and hepatic tissue in hyperlipemia model rats. METHODS ：Male SD rats were randomly divided into blank control group ，model group ，positive control group （simvastatin 0.004 g/kg），Buyang huanwu decoction low-dose and high-dose groups （3.5，14.0 g/kg，by crude drugs），with 10 rats in each group. Except that blank control group was given water intragastrically ，hyperlipidemia mode of other groups was established by intragastric administration of fat emulsion according to the body weight. From the 21st day after modeling，the rats in each group were given water or fat emulsion in the morning and water or corresponding drugs in the afternoon for consecutive 20 days. After last medication ，the contents of TG ，TC，LDL-C，ALT，AST，LCAT，PLTP and HL in plasma were determined in each group ；the contents of LPL ，MTP and HMG-CoA redutase in liver tissue were also determined. The pathological changes of liver tissue were observed in each group. RESULTS ：Compared with blank control group ，the contents of TG ，TC，LDL-C，ALT and HMG-CoA reductase were increased significantly in model group （P＜0.05 or P＜0.01），while the contents of HL ，LPL and MTP were decreased significantly （P＜0.01）. Compared with model group ，the contents of TG ，TC， LDL-C and HMG-CoA reductase in administration groups as well as the contents of ALT ，AST in Buyang huanwu decoction low-dose and high-dose groups were decreased significantly （P＜0.05 or P＜0.01）；the contents of HL and MTP in administration groups as well as the content of LPL in positive control group were increased significantly （P＜0.05 or P＜0.01）. Pathological sections showed that the hepatocytes of model group were arranged irregularly ，and there was obvious cell steatosis. The hepatocytes in positive control group and Buyang Huanwu decoction high-dose group had almost no abnormal change compared with blank control gr oup，and there was a small amount of slight cell steatosis in Buyang Huanwu decoction low-dose group. CONCLUSIONS ： Buyang huanwu decoction has a 础。E-mail：zhang520-888@163.com significant lipid-lowering effect on hyperlipemia model rats ，which may be related to the regulation of lipid absorptiontransport and metabolism by regulating the expression of lipid 126.com metabolism related enzymes and transporter.

OBJECTIVE To investigate the effects and mechanism of Danshen decoction influencing platelet physiological characteristics and function in hyperlipidemia model rats based on platelet membrane glycoprotein 4 （CD36）/phosphatidylinositol 3- kinase （PI3K）/protein kinase B （Akt） signaling pathway. METHODS The hyperlipidemia model rats were induced by feeding high- fat diet， and then randomly divided into model group， simvastatin group （0.004 g/kg）， Danshen decoction high-dose and low-dose groups （3.6， 0.9 g/kg）， and blank group （fed with basic feed）， with 10 rats in each group. Rats in each administration group were intragastrically administered with corresponding drugs every day， and the other groups were intragastrically administered with equal volume of normal saline for 4 weeks. After the last administration， the contents of blood lipid biochemical indexes [total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）]， whole blood viscosity， plasma viscosity and fibrinogen （FIB）content in plasma， platelet-related parameters [platelet count （PLT）， platelet distribution width （PDW） and mean plateletvolume （MPV）] were detected. The levels of plateletphysiological characteristics and function-related factors [von Willebrand factor （vWF）， fibronectin （Fn）， phospholipase A2（PLA2）， thromboxane B2 （TXB2）， 6-keto-prostaglandin F1α （6-keto-PGF1α）， thromboxane A2 （TXA2）， prostaglandin I2 （PGI2）， cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， β-thromboglobulin （β-TG）]， platelet aggregation rate （maximum aggregation rate， 60 s aggregation rate， 180 s aggregation rate） and fibrinolytic system-related factors [tissue plasminogen activator （t-PA）， plasminogen activator inhibitor 1 （PAI-1）] and the expressions of CD36/PI3K/Akt signaling pathway-related proteins [CD36， focal adhesion kinase （FAK）， phosphatidylinositol 4-phosphate 5-kinase （PIP5K）， PI3K， phosphorylated Akt （p-Akt）， p-Akt1/2/3] in platelet were all determined. RESULTS Compared with blank group， the contents of TC， TG and LDL-C in plasma， whole blood viscosity， plasma viscosity， the plasma levels of FIB， PLT， MPV， vWF， Fn， PLA2， TXB2， TXA2， cGMP and β-TG， maximum platelet aggregation rate， 60 s aggregation rate， the expressions of PAI-1 in plasma， protein expressions of CD36， FAK， PIP5K， PI3K， p-Akt and p-Akt1/2/3 were significantly increased in the model group （P＜0.05）. The content of HDL-C and the levels of 6-keto-PGF1α， PGI2 and t-PA were significantly decreased （P＜0.05）. After the intervention of Danshen decoction， most of the above indexes were significantly reversed （P＜0.05）. CONCLUSIONS Danshen decoction can improve the physiological characteristics and function of platelets in hyperlipidemia model rats， and its mechanism may be related to the down-regulation of CD36/PI3K/Akt signaling pathway activity and the reduction of platelet activation.

OBJECTIVE：To investigate the effe cts of Buyang huanwu decoction on hemorheology and platelet related biological indexes of hyperlipidemia model rats. METHODS ：Male Wistar rats were randomly divided into blank control group （10 rats）and model group （40 rats）. Blank control group was given normal diet ，and model group was given high-lipid diet for 6 weeks at least to induce hypelipidemia model. After modeling ，rats were randomly divided into model control group ，positive control group （simvastatin，0.004 g/kg），Buyang huanwu decoction low-dose and medium-dose groups （3.5，14.0 g/kg，by crude drug），with 10 rats in each group. Blank control group and model control group were given normal saline intragastrically ， administration groups were given relevant drug intragastrically ，0.01 mL/g，once a day ，for consecutive 4 weeks. Thirty min after last medication ，hemorheological indexes （whole blood viscosity ，plasma viscosity ），platelet adhesion related indexes [adhesion rate，von Willebrand factor （vWF），fibronectin（FN）]，platelet release related indexes [ β-thromboglobulin（β-TG），platelet factor 4 （PF4）] and platelet fibrinolytic system related indexes [tissue plasminogen activator （t-PA），plasminogen activator inhibitor （PAI-1）]，platelet parameters （PLT，PDW，MPV，PCT，PLCR），4 kinds of coagulation parameters （APTT，TT，PT，FIB）were detected. RESULTS ：Compared with blank control group ，the whole blood viscosity （low，medium and high shear rate ），plasma viscosity，platelet adhesion rate ，the contents or levels of vWF ，FN，β-TG，PAI-1，PLT，MPV，PCT，PLCR and FIB in model control group were increased significantly （P＜0.05 or P＜0.01），and t-PA content was significantly decreased （P＜0.05）. Compared with model control group ，the whole blood viscosity （except for whole blood viscosity of high shear rate in Buyang huanwu decoction high-dose group ），plasma viscosity ，platelet adhesion rate ，the contents or levels of vWF ，FN，β-TG，PAI-1， PLT，PDW（except for Buyang huanwu decoction low-dose and high-dose groups ），MPV，PCT，PLCR（except for Byang huanwu decoction low-dose group ）and FIB were decreased significantly （P＜0.05 or P＜0.01），while t-PA content （except for positive control group ） was increased significantly （P＜0.05）. CONCLUSIONS ：Buyang huanwu decoction can significantly improve the pathological state in hyperlipidemia model rats by reducing blood viscosity and FN content ，improving platelet adhesion，enhancing fibrinolytic activity ，improving platelet aggregation ，inhibiting hypercoagulability and hyperplatelet release.

OBJECTIVE To explore the regulatory mechanism of Danshen decoction on dyslipidemia in hyperlipidemia model rats. METHODS The experimental rats were divided into blank group （n＝9， no modeling）， model group （n＝8， modeling）， and Danshen decoction group （n＝9， modeling）. Starting from the 9th week of feeding with the high-fat diet， rats in the Danshen decoction group were given the corresponding medication solution （3.6 g/kg） intragastrically， while blank group and model group were given equal volume of normal saline， once a day， for 4 consecutive weeks. After 4 weeks of administration， the plasma levels of triglycerides （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured in each group of rats； the pathological and morphological changes of liver tissue were observed； the differential proteins between samples were screened out by TMT quantitative proteomic analysis； the expression levels of the key differentially expressed proteins in the liver， including epoxide hydrolase 2 （EPHX2）， perilipin 2 （PLIN2）， peroxisome proliferator activated receptor γ （PPAR γ） and glycogen synthase kinase-3β （GSK-3β）were detected. RESULTS Compared with the model group， the plasma levels of TC， TG and LDL-C in the Danshen decoction group were significantly reduced （P＜0.05）， while the level of HDL-C was significantly increased （P＜0.05）. The liver tissue of rats inmodel group showed uneven staining， disordered arrangement of liver plates， disappearance of liver sinusoids， nuclearcondensation or disappearance of some cells， swelling and fusion of cytoplasm， proliferation of connective tissue， and diffuse vacuolar-like fat droplet changes. The liver tissue of Danshen decoction group showed varying degrees of improvement in the above pathological and morphological. The results of differential protein analysis showed that the total number of differential proteins was 298 between the model group and the blank group； the total number of differential proteins was 139 between the model group and Danshen decoction group. Compared with the model group， the expression levels of EPHX2 and PLIN2 proteins in the liver tissue of rats in the Danshen decoction group were significantly reduced （P＜0.01）， while the expression levels of GSK-3β and PPARγ were significantly increased （P＜0.01）. CONCLUSIONS Danshen decoction has a significant improvement effect on the plasma lipid levels and the pathological and morphological of the liver tissue in hyperlipidemia model rats. Its regulatory mechanism may be related to the up-regulation of PPARγ and GSK-3β expression and down-regulation of EPHX2 and PLIN2 expression， and the signaling pathways involved may include PPAR-γ signal pathway.

ObjectiveTo decipher the mechanism of Danshenyin in regulating platelet activation in the rat model of hyperlipidemia by means of proteomics and molecular biology. MethodWistar rats were randomized into blank， model， and Danshenyin groups （n=10） according to the blood lipid level. The rats in the blank group were fed with a basic diet， and those in the model and Danshenyin groups with a high-fat diet. All the rats had free access to water and food. The treatment began at the 9th week. The rats in the Danshenyin group were administrated with Danshenyin by gavage at a crude drug dose of 3.6 g·kg^-1. The rats in the model and blank groups were administrated with an equal volume of normal saline according to body weight. At the 12th week， the tissue samples were collected for the measurement of related indicators， and the blood lipid level was measured by an automatic biochemical analyzer. The whole blood viscosity and plasma viscosity were measured by an automatic hemorheometer. The platelet proteome was determined by liquid chromatography-mass spectrometry. Western blotting was employed to determine the protein levels of platelet membrane glycoprotein 4 （CD36）， focal adhesion kinase （FAK）， phosphatidylinositol 4-phosphate 5-kinase （PIP5K）， phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， protein kinase B （Akt）， and phosphorylated protein kinase B （p-Akt）. ResultCompared with the model group， Danshenyin lowered the levels of total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） in the plasma （P<0.05）， elevated the level of high-density lipoprotein cholesterol （HDL-C） （P<0.05）， and reduced the platelet aggregation rate （P<0.05）. Compared with the blank group， the modeling up-regulated the expression of 44 proteins and down-regulated the expression of 12 proteins. Compared with the model group， Danshenyin up-regulated the expression of 21 proteins and down-regulated the expression of 22 proteins. Compared with the blank group， Danshenyin up-regulated the expression of 31 proteins and down-regulated the expression of 49 proteins. The gene ontology （GO） functional enrichment showed that the differentially expressed proteins were mainly involved in cholesterol transport and efflux， production of cytokines， dyslipidemia， and platelet activation. The Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment showed that the differentially expressed proteins were mainly involved in ECM-receptor interaction， peroxisome proliferators-activated receptors （PPAR）， focal adhesion， and PI3K/Akt signaling pathways. Danshenyin can significantly down-regulate the expression of CD36， FAK， PIP5K， PI3K， p-Akt （Ser473）， and p-Akt1/2/3 （Thr308）. ConclusionDanshenyin can restore the blood lipid level of hyperlipidemia rats and inhibit the platelet activation caused by abnormal lipid levels by down-regulating the CD36/PI3K/Akt signal cascade.