The antiumor activity of a new podophyllotoxin spin-labeled derivative, 4 -C 4 "-( 2 ", 2", C", 6"-tetramethyl- 1 "-piperidinyoxy ) amino]-4'-demethylepipodophyllotoxin ( GP-7 ) was studied. It was found that the growth of transplanted mouse tumors S180, HePS and Lewis lung cancer was markedly inhibited by GP-7. At a dose of 7.5-20 mg/kg, the inhibition rates of it against Sl80, HePS and Lewis lung cancer were 36.0-58.4, 29.6-60.0, and 27.2-46.5 % respectively. The toxicity of GP-7 was low, as indicated by the LD50 value of 231.2 mg/kg which was 3.3 times higher than that of etoposide ( VP-16 ) . On the other hand, the effects of GP-7 on spleen index and thymus index of mice bearing S180 tumor were remarkably lower than that of VP-16. In vitro GP-7 exhibited marked inhibition effects against L1210 and SGC-7901 cells. After exposure of L1210 cells to GP-7 and VP-16 5 mg/L for 24 h, the. inhibition rates were 75.5 and 73.6 %. after exposure of SGC-7901 cells to GP-7 and VP-16 5 mg/L for 72 h, the inhibition rates were 81.4 and 84.2 %. The new podophyllotoxin derivative GP-7 was similar to its structure analogues, clinical drug VP-16, in antitumor activity, while the toxicity of it was much lower than that of VP-16.

It was found that the proliferation of mice L7712 leukemic cells in vitro was markedly inhibited by 5 mg/L GP1 and VP10 The inhib itory rate increased with the incubation time. At a concentration of 0 .04-20mg/L, the mitotic index ( MI ) of GP1 group increased, but the MI of VP16 group decreased. After L7712 cells were treated with GP, 5 mg/L for 12 h the MI reached the highest point which was 8 times as high as that of the control, at the same time, the MI of VP16 ( 5 mg/L) group was about one-third of that of the control. The result of the combination of GP1 with VP16 showed that VP16 could antagonize the effect of GP on MI of L7712 cells. After being treated by GP1 and VP18 for 24 h, serious damage of L7712 cells could be observed. Both drugs inhibited the incorporation of (3H) TdR into DNA of S180, ascitic hepatoma (AH), L1210 and L7712 cells incubated for 24 h. It was further observed that S180 and L7712 cells were more sensitive than other cells to both drugs.

Objective To study the expression of intercellular adhesion molecule-1 (ICAM-1 ) in the rat cardiac heterotopic allo- grafts and the effect of cyclosporin A on prevention of allograft rejection. Methods Heart transplantated animals were divided into three groups: Group Ⅰ(control), Group Ⅱ(CsA 7. 5mg/kg B W, daily) and Group Ⅲ(CsA l5mg/kg B W, daily). Acute cardiac rejection grade was valued by the standrd of ISHLT(1990 ). Immunohistochemistry was performed to analyze the expression of ICAM-1 in heart grafts and donor aorta segments. Results After heart transplantation, it was found that from day 1 to 3, there was sligtly inflammatory infiltratiation, the rejection was graded 1A of 1B, But from day 11 to 12, there were disseminated inflammation and cardiac necrosis with serous hyperemia, exutation, edema, acute vasculitis and myocarditis. The rejection grade was 3B or 4, and could be reduced 1to 2. 5 grades by administration of CsA. It was also found that both in heart graft and donor aorta segments the expression of ICAM-1 on the endothelium cells, infiltrated lymphocytes was clearly increased. It was time-dependent and could be down-regulated by administra- tion of CsA. On Day 1 and Day 3 the suppressing function of CsA on expressing of ICAM-1 showed singificant dosage-dependent. But from Day 7 to Day 11, it appeared dosage- independent. Conclusiou Trea tment with CsA is an effect ive methed to down- regulate I - CAM-1 expression and could reduce the lympphocyte migration and filtration. These results may explain, in part, the mechanism of CsA reducing acute rejection in a rat cardiac transplantation medel.

Objective 　To investigate the prevalence, characteristics and correlates of depressive symptoms in first episode schizophrenic patients. Methods　To examine 164 first episode schizophrenic patients at the time of admission and at 3,6,9, and 12 months after starting treatment using the HAMD, BPRS, the Chinese version of SANS, CGI and GAF. Results　71% of the patients had depressive symptoms (mild or more) at damission, but the prevalence of depressive symptoms dropped to a mean of 12% during the recovery period. The most prominent depressive symptoms during the acute phase of schizophrenia were ‘cognitive disturbance’ and ‘retardation’ (the respective subscales constituted 35% and 29% of the total HAMD score on admission). Depressive symptoms improved in parallel with the schizophrenic illness. The severity of depressive symptoms was not related to gender, age of onset, educational level, duration of prodromal period or duration of illness. At admission the severity of depressive symptoms was only related to the BPRS anxiety and depression subscale score, but during the recovery period the HAMD total score was significantly correlated with all of the other clinical scales. The level of depressive symptoms at admission and at three months after starting treatment was not related to the subsequent course of positive or negative symptoms. Conclusions　Depressive symptoms appeared to be a separate symptom cluster during the acute phase of first episode schizophrenia. The severity of depressive symptoms did not predict the clinical outcome of first episode schizophrenic patients.

Objective To investigate the influence of the different degree of internal carotid stenosis on the white matter lesion and cognition of Binswanger disease.Methods A total of 108 elderly patients with Binswanger disease from Department of Geriatric Neurology of Qilu Hospital were recruited during December 2013 and June 2014.At the end of follow-up,6 cases showed acute eerebrovaseular disease,39 (＜ 10 ％) had no internal carotid stenosis,31 (10 ％-49 ％) had mild internal carotid stenosis,32 (50％-70％)had moderate internal carotid stenosis through B ultrasound examination and MRI and MRA examination on internal carotid artery and brain.The B ultrasound examination of internal carotid artery included intima-media thickness (IMT),plaque index and the peak systolic velocity (PSV).Cognitive function of Binswagner disease was assessed by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MOCA).The white matter lesion was assessed by reformed visual Scheltens scale.The relationship among IMT,plaque index,PSV,white matter lesion,and cognitive function was investigated.The variation of cognition was observed after 1 year.Results There were statistically significant differences in IMT,PSV,plaque index,reformed Scheltens scale scores between groups of non,mild,moderate internal carotid stenosis (all P ＜0.05).The IMT was thicker in moderate internal carotid stenosis group than in mild internal carotid stenosis group (P＜0.05).The differences in PSV,plaque index,and reformed Scheltens scale scores between mild and moderate internal carotid stenosis groups were not significant (P＞0.05).There were positive correlation between PSV and reformed Scheltens scale scores (r=0.630,P =0.020).There were negative correlation between PSV and MMSE scores (r=-0.970,P=0.040).The scores of MMSE and MOCA both were declined after 1 year in three groups (0.61 ± 0.60,0.68 ± 0.81),(0.70±0.60,0.93±0.69),(1.06±0.68,1.13±0.76).The declination of MMSE and MOCA of BD patients was higher in moderate internal carotid stenosis group than in non internal carotid stenosis group (P＜0.05).The differences in the declination of MMSE and MOCA between moderate and mild internal carotid stenosis groups were not significant (P＞ 0.05).Conclusions Internal carotid stenosis is one of risk factors for the cognitive impairment of BD,the abnormal IMT and PSV are both correlated with white matter lesion and cognitive impairment in BD.Early standardized therapy can postpone the rate of cognitive impairment in BD.

Objective To study the protective effects of tBHQ on type 2 diabetic rats retina and its related mechanism.Methods Sixty SD rats were divided into normal control group (NC group),model group (diabetes mellitus,DM group) and tBHQ group.After feeding with high fat and high sugar diets for 4 weeks,the rats in model group were induced by intraperitoneal injection of STZ for the model of type 2 diabetes mellitus.1％ tBHQ were added into the high fat and high sugar feed 1 week later after successfully modeled in the tBHQ group.Fasting plasma glucose (FPG) and fasting serum insulin (FINs) were detected at 4 and 12 weeks after modeled.Immunohistochemical method and real-time fluorescent quantitative PCR (qRT-PCR) were respectively used to detect the distributions and relative expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2),heme oxygenase 1 (HO-1),B-cell lymPhoma 2 (Bcl-2) and vascular endothelial growth factor (VEGF) in retinas of the rats.Results FPG levels totally comparative differences were statistically significant between each group (F =78.531,P =0.000).The level of FPG in DM and tBHQ group were obviously higher than that in NC group,the 12 weeks was higher than 4 weeks in DM group,and the 12 weeks was lower than 4 weeks in tBHQ group (all P ＜ 0.05).Totally comparative differences in the level of FINs were statistically significant (F=22.480,P =0.000),NC group was lower than DM and tBHQ group,12 weeks was higher than 4 weeks (all P ＜ 0.05).Immunohistochemical detection showed that each factor in each group were expressed in the retina of rat,and the relative expressions of Nrf2,HO-1,Bcl-2 and VEGF protein in retina have totally statistically differences in different time points after modeled (all P ＜0.05).The expressions of each factor in DM group were more than those in the NC group.The Nrf2,HO-1 and Bcl-2 in tBHQ group were more than those in the DM group,but the VEGF was lower.At 12 weeks,the expressions of VEGF and Nrf2 in DM group were more than those at 4 weeks,but the HO-1 was lower;the Nrf2,HO-1 and Bcl-2 in tBHQ group were more than those at 4 weeks (all P ＜ 0.05).PCR tests revealed that the relative expressions of Nrf2,HO-1,Bcl-2 and VEGF mRNA in retina have totally statistically differences in different time points after modeled(all P ＜ 0.05).The expressions of each factor in DM group were more than those in the NC group.The Nrf2,HO-1 and Bcl-2 mRNA in tBHQ group were more than those in the DM group,but the VEGF mRNA was lower.At 12 weeks,VEGF mRNA in DM group and Nrf2,HO-1,Bcl-2 in tBHQ group were more than those at 4 weeks (all P ＜ 0.05).Conclusion tBHQ maybe have protection for islet function on diabetic rat,and can induce the expressions of Nrf2,HO-1,Bcl-2 in retina of diabetic rats and reduce the expression of VEGF,inhibit the oxidative stress of retinal tissue damage,reduce cell apoptosis and inhibit the proliferation of retinal blood vessels.tBHQ may protect the retina of diabetic rats through the Nrf2/HO-1/VEGF and Nrf2/Bcl-2 way.

Objective To investigate the effect of diabetes on short-term prognosis of transient ischemic attack (TIA) in elderly patients.Methods From January 2006 to June 2010,126 patients with TIA aged over 60 years were selected.Patients were divided into diabetic group and non-diabetic group according to past history,blood glucose and glycosylated hemoglobin levels.The cumulative ischemic stroke incidences were analyzed by Kaplan-Meier survival analysis 30 days and 90 days after the first TIA.The risk factors for short-term stroke after TIA were analyzed by Cox regression analysis.Results Among 126 patients with TIA,31 cases (24.6％) had diabetes.The cumulative ischemic stroke incidences were significantly higher in diabetic group than in non-diabetic group 30 days and 90 days after the first TIA (54.8％ vs.22.1％,61.3％ vs.28.4％,both P＜0.01).Cox regression analysis revealed that diabetes and cerebral arterial stenosis were the risk factors for recurrent stroke within 90 days.Conclusions The short-term stroke incidence is significantly higher in elderly diabetic patients than in non-diabetic patients.Diabetes is the independent risk factor for recurrent stroke after TIA.

[Objective]To investigate the prognostic value of 18F-FDG PET/CT with different metabolic parameters in newly diagnosed limited-disease(LD)small cell lung cancer(SCLC).[Methods]Retrospective analysis was carried out in the patients between June 2005 to December 2016 in our hospital confirmed of LD SCLC by pathology or cytology and comprehensive imaging. Fifty-four patients were recruited. Record the general characteristics of patients,pre-treatment KPS score,smoking status,weight loss,serum LDH,NSE,OS,PFS. All lesions(primary lesions + metastases)were sketched out within one VOI,and the SUVmax, SUVmean and SUVpeak in the VOI were automatically measured and recorded. The automatic measurement was performed by the fixed threshold method. The thresholds of tumor of MTV and TLG were 40% and 50% of SUVmax. The TLG and MTV were identified as TLG40%,TLG50%,MTV40% and MTV50% respectively. Kaplan-Meier method was used for survival analysis. All the prognostic factors were analyzed by Cox model.[Result]The median SUVmax was 13.92(2.61~43.28),the median of SUVmean was 8.31(1.71~26.85) and the median of SUVpeak was 10.51(1.49 ~ 27.48). The median of TLG40% was 340.22(16.58 ~ 2827.26),the median of TLG50%was 215.645(1.70 ~ 2270.36),the median of MTV40% was 36.71(1.15 ~ 259.47 cm3),the median of MTV50% was 19.65(0.93 ~1900.00)cm3. Univariate and multivariate analysis of metabolic index and prognosis showed that TLG50% was the prognostic factor of OS(P = 0.013),but not of PFS(P > 0.05). The SUVmax,SUVmean and SUVpeak were not the prognostic factors of OS and PFS(P >0.05).[Conclusion]The volume metabolic parameters TLG50%was the independent prognostic factor of the overall survival time of the LD SCLC. The volume metabolic parameters (TLG and MTV) of 18F-FDG PET/CT were related to the prognosis of SCLC ,which could provide the basis for individual chemotherapy.

han that in the control one (t=3.94, P<0.01).Conclusion Social skills training can effectively improve subjective satisfactions of the long-terra hospitalized patients with chronic schizophrenia.

Background Apoptosis is a primary clinical pathological mechanism of diabetic retinopathy (DR).Oxidative stress and high glucose can activate cell apoptosis pathway and thus leads to cellular damage.It is confirmed that tert-butyl hydroquinone (tBHQ) plays an antioxidation effect,however,whether it has a protective role on retinal cells in DR is still unelucidated.Objective This study was to investigate the effect of tBHQ on vascular endothelial growth factor (VEGF) and bcl-2 expressions in retina of type 2 diabetic rats and its possible mechanism via nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signal pathway.Methods Fifty clean healthy male SD rats were included in this experimental study.Ten rats were fed with normal diet as the normal control group,and other rats were fed with high fatty and high sugar food for 4 weeks.After 12 hours of fasting,streptozotoin (STZ) (30 mg/kg) was intraperitoneally injected to induce the type 2 diabetic models.The model rats were randomly divided into the diabetic control group and tBHQ group and 1％ tBHQ was added into the high fatty and sugar food 1 week after modeling in the tBHQ group.Fasting plasma glucose (FPG) level,blood total cholesterol (TC) level,blood triglyceride (TG) level,high density lipoprotein-cholesterol (HDL-C),low density lipoproteincholesterol (LDL-C) and fasting serum insulin (FINs) were detected 4 and 12 weeks after modeling,respectively,and radio immunoassay was used to detect the FIN levels of the rats.The relative expression of VEGF and bcl-2 in retinas of the rats were assayed by immunohistochemistry and fluorescence real-time quantitative PCR (qRT-PCR).The use of the animals complied with the Regulations for the Administration of Affairs Concerning Experimental Animals by State and Technology Commission.Results Type 2 diabetic models were successfully established in 35 rats with successful rate 92.1％.The FIN levels were significantly different among different groups and time points (Fgroup =22.480,P =0.000;Ftime =7.636,P =0.008).The FPG,TC,TG and LDL-C levels were significantly different among the groups (FPG:Fgroup =78.531,P =0.000;TC:Fgroup =28.049,P =0.000;TG:Fgroup =13.108,P =0.000;LDL-C:Fgroup =6.804,P＜0.05).Immunohistochemistry showed that VEGF and bcl-2 were mainly expressed in retinal ganglion cell layer,inner plexiform layer and outer plexiform layer.The expressions of VEGF and bcl-2 proteins were significantly different among different groups (VEGF:Fgroup =11.805,P =0.000;bcl-2:Fgroup =22.943,P =0.000);the expression level of bcl-2 protein was higher in 12 weeks after modeling than that in 4 weeks after modeling in the tBHQ group (P＜0.05).The expressions of VEGF and Bcl-2 mRNA in rat retinas were significantly different among different groups and time points (VEGF:Fgroup =79.220,P =0.000;Ftimo =6.090,P＜0.05;Bcl-2:Fgroup =105.000,P=0.000;Ftime =13.170,P=0.001).Four and eight weeks after modeling,the expressions of VEGF and Bcl-2 mRNA in the diabetic control group and tBHQ group were significantly higher than that in the normal control group,and the expressions of Bcl-2 mRNA in the tBHQ group were significantly higher than that in the model control group (all at P＜0.05);the expression of Bcl-2 mRNA was higher at 12 weeks after modeling than that at 4 weeks in the tBHQ group (P＜0.05).Conclusions tBHQ produces anti-oxidative-damage and anti-apoptosis effects on retinal cells by up-regulating VEGF expression and down-regulating bcl-2 expression in DR rats.In addition,tBHQ may have effects on lowering high blood sugar,regulating insulin and blood lipid levels.