OBJECTIVE:To provide reference for improving the clopidogrel rational use in cerebral infarction secondary preven-tion. METHODS:Medical cases of 471 patients with acute cerebral infarction in neurology department in a hospital from 2013 to 2014 were retrospective surveyed to collect the utilization rate of clopidogrel and the combination of clopidogrel with proton pump inhibitors(PPIs)and aspirin,and the rationality was analyzed. RESULTS:The utilization rate of clopidogrel in cerebral infarction secondary prevention was 93.84%;the combination rate with PPIs was 52.49%,of which,51.72% had no drug selection or com-bined treatment basis;the combination rate with aspirin was 40.72%,cardiogenic cerebral infarction accounted for only 3.9%, non-cardiogenic cerebral infarction accounted for 96.1%,and recurrence of cerebral infarction in high-risk patients accounted for 31.11%. CONCLUSIONS:Clopidogrel in patients with cerebral infarction secondary prevention is widely used in the hospital,has high combination rate with PPIs and aspirin and low guide compliance rate. Clopidogrel should be enhanced pharmacy services, comply with evidence based medicine and improve the rationality of medication.

AIM: To observe the dynamic changes of plasma levels of nitric oxide(NO) and endothelin (ET-1) in portal veins of the rats during prehepatic portal hypertension, and investigate the role of them in hyperdynamic circulation. METHODS: The models of prehepatic portal hypertension were established in Sprague-Dawley rats by means of partial portal vein ligation (PVL). The plasma levels of nitrite/nitrate (NO - 2/NO - 3) and ET-1 in the portal veins were detected by the method of nitric reductase and radioimmunoassay, respectively. In this study, rats were divided into normal, sham operation (SO) and PVL group. SO and PVL rats were divided into several subgroups according to different time after operations. Meanwhile, the changes of several hemodynamic indexes in these rats were also measured. RESULTS: The levels of NO - 2/NO - 3 were significantly increased and ET-1 were significantly decreased in rats at different time after PVL compared with normal control, whereas the hemodynamic indexes changed accordingly. CONCLUSION: The portal hypertensive rats are in hyperdynamic circulatory state (HCS). NO and ET-1 may play an important role in the induction and maintenance of HCS.

ObjectiveTo prospectively investigate the impact of short-time response on survival of concurrent chemotherapy and thoracic three-dimensional radiotherapy (CCTTRT) for stage Ⅳ non-small cell lung cancer (NSCLC). Methods From Jan.2003 to Oct.2010,201 patients with pathologically or cytologically proven stage Ⅳ NSCLC were included.All patients received platinum-based chemotherapy.Of the 167 patients eligible for analysis,the median number of chemotherapy were 4 cycles.The median dose for planning target volume (PTV) of thoracic primary tumor was 63 Gy.Response was scored according to WHO criteria. Survival was calculated by Kaplan-Meier method and compared using the Logrank. Cox regression model were used to examine the effect of response on overall survival.ResultsThe follow-up rate of 201 patients was 97.5％.with 201,170 and 134 patients finished ＜ 1,1 -2 and ≥3 years' follow-up.For the 167 patients eligible for analysis,the CR,PR,NC and PD rate of primary tumor was 5.4％,65.9％,21.0％ and 7.7％,respectively.The effective group ( CR + PR) and ineffective group ( NC + PD) was 71.3％ and 28.7％,respectively.The median survival time (MST) for patients with CR,PR,NC and PD was 22.6,13.4,8.8 and 4.8 months,respectively ( χ2 =44.79,P =0.000).The MST for effective and ineffective group was 13.9 and 7.6 months,respectively in the whole group ( χ2 =8.3 0,P =0.004 ),12.1months and 7.3 months in those treated with 2 - 3 cycles chemotherapy ( χ2 =7.71,P =0.007 ),and 13.9months and 7.9 months in those treated with 2 -5 cycles chemotherapy and radiation dose to PTV ≥36 Gy ( χ2 =4.00,P =0.045 ).No significant MST difference was detected between patients of effective group and ineffective group treated with 4 -5 cycles chemotherapy ( χ2 =0.67,P =0.413),or those treated with 4 -5 cycles of chemotherapy and radiation dose to primary lesion ≥36 Gy (χ2 =0.00,P =0.956).Multivariate analysis showed that 4-5 cycles of chemotherapy and CR and PR achieved in primary tumor (β =0.182,P=0.041 ) were independent favorable factors for survival. Conclusion CCTTRT can improve local control,and prolong the survival time for Stage Ⅳ NSCLC.

Aim To investigate the reversal effect of vatalanib, a novel kinase inhibitor, on multidrug re-sistance in cancer cells and its mechanism. Methods The cytotoxicity and reversal effects of vatalanib were evaluated in both resistant and sensitive tumor cell lines by MTS or SRB assays. The intracellular accumu-lation of fluorescence substrates ( Rh-123 , MX and ADR for P-gp, BCRP, MRP1, respectively) were ana-lysed by flow cytometry. Western blot or qRT-PCR was
used to determine the protein or mRNA expression lev-el of BCRP. The effect of vatalanib on ATPase activity of BCRP was determined using crude membranes pre-pared from HEK293/ABCG2 cells. Results Vata-lanib at the nontoxic dose ( 5 μmol · L-1 ) potentially reversed BCRP-mediated MDR in cancer cells, howev-er it had no effect on P-gp or MRP1 mediated MDR. Vatalanib did not alter the intracellular accumulation of MX in HEK 2 9 3 / ABCG 2 , and had no influence on the
BCRP-mediated drug efflux. The ATPase assay indica-ted that vatalanib may serve as a substrate of BCRP. Furthermore, vatalanib dramatically suppressed levels of both the protein and mRNA expression of BCRP in concentration-and time-dependent manners. However, reversal concentration of vatalanib had no influence on the total and phosphorylated forms of AKT and ERK1/
2 in resistant cancer cells. Conclusion Vatalanib could significantly reverse BCRP-mediated MDR with specificity, and its mechanism may correlate with the down-regulation levels of BCRP both mRNA and pro-tein in resistant cancer cells.

Objective To prospectively evaluate the survival of different metastasis organs with concurrent chemotherapy and thoracic three-dimensional radiotherapy (CCTTRT) for stage Ⅳ non-small cell lung cancer (NSCLC).Methods Two hundred and one patients of stage Ⅳ NSCLC were enrolled from January,2003 to July,2010.Of the 182 patients eligible for analysis,The number of patients with single-organ metastasis or multiple-organ metastasis was 107 and 75,respectively.Patients were treated by platinum-based chemotherapy,the median number of cycle was 4.The median dose to planning target volume of primary tumor (DTPTv) was 63 Gy.Survival was calculated by Kaplan-Meier method and compared using the Logrank.Results The follow-up rate of 201 patients was 97.5％.with 201,170 and 134 patients finished ＜ 1,1 -2 and ≥3 years'follow up.Of 182 patients,the 1-,2-,and 3-year overall survival (OS) rate and median survival time (MST) was 41.0％,17.0％,10.0％ and 10.5 months,respectively ;with single-organ metastasis and multi-organ metastasis were 50％,20％,14％ and 13 months and 29％,12％,0％ and 8.5 months ( x2 =10.10,P =0.001 ),respectively; compared with multi-organ metastasis,the 1-,2-,and 3-year OS arte and MST of patients with bone,lung metastasis only was 58％,25％,16％ and 14 months (x2 =10.42,P=0.001 ) and 49％,21％,21％ and 11 months (x2 =6.39,P=0.011 ) respectively;patients with brain metastasis only did not show advantage of survival comparing with patients with multi-organ metastasis (49％,8％,0％ and 12 months and 29％,12％,0％ and 8 months,respectively;x2 =0.71,P =0.401 ) ;the 1-,2-,and 3-year OS rate and MST was 63％,23％,19％ and 15 months and 42％,15％,0％ and 10 months,respectively for patients with single-organ metastasis and multi-organ metastasis patients who accepted 4 - 5 cycles of chemotherapy ( x2 =6.47,P =0.011 ) ; for patients under the same metastasis and 4 - 5 cycles of chemotherapy,no matter whether single-organ or multiple-organ metastases,the 1 -,2-,3-year OS rate and MST of patients with enough radiotherapy on DTPTV ≥63 Gy were better than patients without enough radiotherapy ( DTPTV ＜ 63 Gy ) ( 71％,25 ％,25％ and 16.8 months and 33％,17％,0％ and 10.5 months,respectively;x2 ＝4.73,P =0.030 ;54％,21％,0％ and 14.3 months and 29％,10％,0％ and 7.6 months,respectively,x2 =8.16,P =0.004).The MST of liver metastases was 6 months,there was significantly difference when comparing with non liver matastasis ( x2 =17.21,P =0.000).Conclusions It is very important to treat stage Ⅳ NSCLC with CCTTRT,especially patients with single-organ metastasis.Liver metastases is a unfavorable prognostic factor.

Objective To evaluate the overall survival and safety among patients for stage Ⅳ non-small cell lung cancer (NSCLC) treated with concurrent chemotherapy and thoracic three-dimensional radiotherapy (CCTTRT).Methods From Jan.2003 to July 2010,201 patients with stage Ⅳ NSCLC were included.All patients were treated with CCTTRT.Those patients who received only one cycle chemotherapy were not included in survival analysis,but analysis of toxicity.One hundred and eighty-two patients were eligible for survival analysis.All patients received platinum-based two-drug chemotherapy.The median number of cycles was 4.The median dose to planning target volume of primary tumor ( DTPTV ) was 63 Gy.Treatment-related gastrointestinal and hematological toxicity were scored according to WHO criteria.Radiation-related pneumonitis and esophagitis were evaluated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTC) version 3.0.Survival was calculated by Kaplan-Meier method and compared using the Logrank.Cox regression model was used to examine the effect of CCTTRT on overall survival.Results The follow-up rate of 201 patients was 97.5％.with 201,170 and 134 patients finished ＜ 1,1 -2 and ≥3 years' follow-up,respectively.Of the 182 patients eligible for survival analysis,further stratified analysis showed that the 1-,2-and 3-year overall survival rate and median survival time (MST) was 54％,20％,13％ and 14.3 months,respectively for patients treated with concurrent 4 -5 cycles chemotherapy and CCTTRT,and 66％,23％,19％ and 16.1 months,respectively for those treated with 4 -5 cycles chemotherapy and DTPTV ≥ 63 Gy.Under similar chemoradiotherapy intensity,the MST of patients with single organ metastasis was significantly longer than that with multiple organ metastases ( 13.0 months versus 8.5 months,x2 =10.10,P =0.001 ).For patients eligible for survival analysis and received 4 - 5 cycles of systemic chemotherapy,MST of patients treated with DTPTV≥63 Gy was significantly longer than those treated with DTPTV ＜63 Gy[14.9 months vs.8.4 months (x2 ＝20.48,P =0.000) and 16.1 months vs.8.8 months ( x2 =11.75,P =0.001 )].For patients with single organ metastasis,MST was 16 months for those treated with DTPTV ≥63 Gy and 9 months for those with DTPTV ＜63 Gy (x2 =10.51,P=0.000) ;for patients with multiple organ metastasis,it was 11 months and 7 months,respectively ( x2 =7.90,P =0.005 ).Multivariate analysis showed that concurrent 4 - 5 cycles chemotherapy and DTPTV ≥63 Gy (β =0.243,P=0.019) and improved KPS (β =1.268,P=0.000) were independent factors for survival.For the whole group,45％ patients had Grade 2 -3 gastrointestinal toxicity,35.0％ grade 3- 4 leukopenia,18％ grade 3- 4 thrombocytopenia.15.0％ grade 3- 4 anemia,9.5％ Grade 2 - 3 radiation pneumonia and 13.4％ radiation esophagitis,respectively.Conclusions For stage Ⅳ NSCLC,CCTTRT can prolong survival time with acceptable toxicity.Radiotherapy to thoracic primary tumor should be under consideration.

Objective To evaluate the importance of three-dimensional radiotherapy for elderly patients of stage Ⅳ non-small cell lung cancer (NSCLC).Methods Comparing with treatment outcome of ≥65 years 67 patients and ＜ 65 years 134 patients using concurrent chemotherapy and thoracic threedimensional radiotherapy during 2003 to 2010 years.Survival analysis was taken by Kaplan-Meier method.The multivariate prognosis was analyzed by Cox model.Results The follow-up was 97.8％.The percentage of ≥65 years and ＜ 65 years patients accepted with concurrent 4-5 cycles chemotherapy were 30％ and 55％,and with 42％ and 49％ patients with radiotherapy ≥63 Gy.The median survival time (MST) were 17 months and 14 months (x2 =0.76,P =0.384) for ≥65 years and ＜ 65 years patients accepted with concurrent 4-5 cycles chemotherapy concurrent ≥63 Gy radiotherapy respectively.The MST and 1-,2-,3year overall survival rate were 17 months and 8 months,65％ and 23％,30％ and 13％,24％ and 9％(x2 =7.90,P =0.005) for whole groups patients treated with chemotherapy concurrent ≥63 Gy and ＜ 63 Gy radiotherapy.And the MST of patients ≥ 63 Gy was significantly longer than those with ＜ 63 Gy either concurrent chemotherapy any cycles (x2 =9.54,P =0.023).The MST were 14 months and 8 months (x2 =1.82,P=0.178),17 months and 17 months (x2 =0.47,P=0.492) for ≥ 65 years and ≥ 63 Gy radiotherapy patients accepted with concurrent 4-5 cycles and 2-3 cycles chemotherapy concurrent respectively.Multivariate analysis showed local response (β =0.600,P =0.003) and numbers of tumor metastasis (β =0.670,P =0.040) were independent factors for survival.Conclusions For a part of elderly patients of stage Ⅳ NSCLC,concurrent chemotherapy and thoracic three-dimensional radiotherapy can prolong survival time with acceptable toxicity.Perhaps radiotherapy is more important.

ObjectiveTo explore the effect of radiation dose on survival for stage Ⅳ non-small cell lung cancer (NSCLC) treated with concurrent chemotherapy and thoracic three-dimensional radiotherapy (CCTTRT).Methods From Jan.2003 to Jul.2010,201 Stage Ⅳ NSCLC patients were enrolled.Nineteen patients who received only one cycle chemotherapy were not included in survival analysis.Of the 182 patients eligible for survival analysis,all patients received platinum-based chemotherapy of two drugs.The median number of cycles was 4.The median dose to planning target volume of primary tumor ( DTPTV )was 63 Gy. Survival was calculated by Kaplan-Meier method and compared using the Logrank. Cox regression models were used to examine the effect of DTPTV on overall survival.ResultsThe follow-up rate of 201 patients was 97.5％.with 201,170 and 134 patients finished ＜ 1,1 -2 and ≥3 years' follow-up.The 1-,2-,3-year overall survival rate and median survival time was 20％,14％,0％ and 7.1 months;27％,10％,3％ and 9.6 months;and 59％,22％,16％ and 14.9 months,respectively for patients treated with DTPTV ＜ 45.0 Gy,45.0 - 62.1 Gy and ≥63.0 Gy,respectively ( χ2 =27.88,P =0.000 ) ;43％,19％,0％and 1 1 months and 2 0 ％,1 1％,5 ％ and 8 months,respectively for those received 2 - 3 cycles of chemotherapy and radiation dose ≥63 Gy and ＜ 63 Gy,respectively (χ2 =2.99,P =0.084) ;66％,23％,19％ and 16 months and 29％,12％,0％ and 8.8 months,respectively for those received 4 - 5 cycles chemotherapy and radiation dose ≥ 63 Gy and ＜ 63 Gy,respectively (χ2=15.87,P=0.000).No significant difference was found for patients received 2 - 3 cycles chemotherapy concurrently with DTP,Tv ≥63 Gy and 4 -5 cycles chemotherapy concurrently with DTPTV ＜63 Gy,respectively (χ2 =1.93,P =0.165).Multivariate analysis showed that 4 -5 cycles chemotherapy concurrently with DTPTv ≥63 Gy ( β =0.243,P =0.019),and improved KPS after treatment ( β =1.268,P =0.000) were independent favorable factors for survival.ConclusionChemotherapy concurrent with CCTTRT can prolong survival time of patients with stage Ⅳ NSCLC,especially for those treated with DTPTV ≥63 Gy.

Objective To observe the effect of fastigial nucleus stimulation(FNS)on heart rate variability(HRV)of surgically induced myocardial infarction rats.Methods 100 Sprague-Dawley rats were randomly allocated in four groups,including sham-operation control group,rats with coronary arteries ligated but fastigial nucleus(FN)sham stimulated(AMI group),rats both coronary arteries ligated and FN stimulated(FNS group),and rats on which FN lesioned 5 d before,then coronary arteries ligated and FN stimulated(FNL group).HRV characteristics were determined 6 h,1 d,7 d and 21 d after the ligation,and mortality rates were observed after 21 d.Results FNS can improve the survival of myocardial infarction rats,and this may be due to the increased vagal tone and decreased sympathetic tone.Conclusion FNS may have cardio-protective effects on surgically induced myocardial infarction rats.

The transcriptional repressor RE1 silencer transcription factor(NRSF/REST) is an important factor that restricts some neuronal traits in neurons.Since these traits are also present in pancreatic islet cells,NRSF-regulated genes involved in islet function are searched.A NRSE-like motif was analysed in human insulin promoter.The role of NRSE was evaluated by generating a model of insulin-secreting cells that firmly express NRSF.The presence of NRSF led to a decrease in activity of human insulin promoter by stable or transient transfection with human insulin-promoter luciferase.The predicted NRSE-like motif also confers NRSF-dependent transcriptional repression in the context of a surrogate gene promoter.Specific binding activity of NRSF/REST to the NRSE-like motif was confirmed by EMSA.Moreover,the binding activity is competed by consensus NRSE sequence.These data showed that human insulin promoter is regulated by the transcriptional repressor NRSF/REST via the NRSE-like motif.