Objective To investigate the effects of ursolic acid on the expression of extracellular signal regulated kinase(ERK1),C-Jun,C-Myc,Cyclin D1 in transplanted tumor of malignant glioblastoma cell line C6 in nude mice and the related mechanisms.Methods C6 glioblastoma cells were subcutaneously injected into nude mice to establish the subcutaneous model of glioblastoma in nude mice,and then the mouse models were divided into 3 groups: blank control group,ursolic acid group(50 mg?kg-1?d-1,intra-abdominal injection,20 d),PD98059 group(2 mg?kg-1?d-1,intra-abdominal injection,7 d).Survival of nude mice,growth and histopathological changes of the tumors were observed.The expressions of ERK1,C-Jun,C-Myc,and Cyclin D1 in the tumor tissues and the expression of ERK1 mRNA in the tumor tissues were detected by immunohistochemical technique(IHC) and in suit hybridization(ISH),respectively.Results Slow growth of the implanted tumor was found in ursolic acid group and PD98059 group.The mean volume and weight of tumors in the two groups were significantly smaller than those in the blank control group(P

ObjectiveTo investigate the therapeutic effects of advanced lung adenocarcinoma treated with TCM treatment based on syndrome differentiation combined with Gefitinib.MethodsAll cases were recruited from adenocarcinoma of lung patients in Hunan Province Cancer Hospital from February 2008 to February 2010.These 56 adenocarcinoma of lung patients were randomly divided into a treatment group (30cases) and a control group (26 cases).The control group was treated with Gefitinib,250 mg/d,until the disease getting progress or the patient showing intolerable untoward reaction; while the treatment group was treated with TCM syndrome differentiation based on the control group.ResultsAfter the treatment,the total therapeutic effects was 90.00％ in the treatment group than 65.38％ in the control group (x2=5.40,P＜0.05); symptoms score in both group decreased after the treatment,comparing with the same group before the treatment,with the difference was statistical significance (tthe treatment group=9.2446,tthe control group=2.7778,both P＜0.01) ;non-progressive survival rate of half year,1year and 2year was 66.67％,50.00％ and 30.00％ respectively,and survival rate of lyear and 2yenr was 73.33％ and 46.67％ respectively,in the treatment group,while non-progressive survival rate of half year,lyear and 2year was 38.46％,23.08％ and 7.69％ respectively,and survival rate of 1year and 2year was 46.15％ and 19.23％ respectively,in the control group,showing statistical difference between the two groups (x2 value was 4.46、4.31、5.44、4.31、5.27,P value was 0.03、0.04、0.02、0.04、0.02,all P＜0.05 ) ; the effective power of KPS was 76.67％ and 46.15％ in the treatment and the control group respectively,showing statistical difference(x2=6.24,P＜0.05) ; both groups were absent of such side effects of hematology,heart,liver and kidney toxicity,and interstitial pneumonia,but the incidence rate of Ⅱ ～ Ⅲ degree rash and diarrhea was significantly decreased in the treatment group,comparing with the control group(x2=4.49、4.37,P＜0.05 ).ConclusionThe therapy of TCM treatment based on syndrome differentiation combined with Gefitinib can improve living quality,control aggravation of disease,prolong life span and enhance survival rate of the patients with advanced lung adenocarcinoma.

AIM:To evaluate the morphological and functional changes of retinas induced by treatment of tunicamycin with optical coherence tomography (OCT) in rats.METHODS:Totally 60 SD rats were randomly divided into 3 groups (20 in each group), 0.5mg/kg (in low dose group), 1.5mg/kg (in high dose group) tunicamycin were injected into vitreous cavity and saline (9g/L NaCl) were injected in the same dose as a control group.Changes of retinas were observed by OCT on the 1,7 and 14d after treatment of tunicamycin.Then the rats were sacrificed, retinas were taken out and embedded by the paraffin, tissue sections and the HE staining were performed.RESULTS:OCT results suggested that tunicamycin played damage effects on retinal morphology and structure which appeared a time-and dose-dependent.Fundus photography results suggested that 2wk after tunicamycin treatments, with the gradually changing of tunicamycin concentration, peripheral retinal and macular region became pale color gradually, edema occurred in optic disk, retinal vessels appeared thinner in the high dose group, optic nerve came out atrophy.Fluorescein angiography confirmed that tunicamycin injection in vitreous cavity 2wk later, retinal vessels injury occurred, resulted in leaking of intravascular contrast agent from peripheral to the central part of the retinas.Electrophysiological data showed that retinal electrogram occurred disorder induced by tunicamycin, such as the amplitude of a wave, b wave decreased gradually, even closed to zero, which was very different from control significantly (P<0.05).HE staining of paraffin sections showed that retina injuries induced by tunicamycin were in dose-time dependent, which was consistent with the results of OCT.CONCLUSION: Clinical retinal diseases could be simulated by retinal damage animal model induced by tunicamycin treatment.OCT detection offered real-time images of the retinal cross-section, which provided a helpful non-invasive method for detecting and evaluating the retinal damages.

Objective To investigate the expression of paired box2(Pax2),proliferation cell nuclear antigen(PCNA) and cell apoptosis in steroid-sensitive and steroid-resistant groups with primary nephrotic syndrome(PNS) and to find out the action of Pax2 expression in PNS with steroid-resistance.Method The expressions of Pax2,PCNA were evaluated by immunohistochemistry and cell apoptosis by fluorescence micoscope.Results Pax2 expression in renal tubule had a positive correlation with PCNA expression in steroid-sensitive group.In steroid-resistant group,Pax2 expression had no correlation with PCNA.Pax2 had a negative correlation with cell apoptosis.Conclusions Pax2 proper expression facilitate PCNA expression and repair tubulointerstitial lesions in steroid-sensitive group.Renal tubular epithelial cell proliferation coordinated with cell apoptosis.Pax2 overexpression in steroid-resistant group lead to the decrease of cell proliferation and cell apoptosis and lead to the severe tubule lesions,which made to glucocorticoid resistance.

Objective To investigate the association between the plasma level of fibrinogen and carotid atherosclerosis(CAS)in patients with ischemic cerebrevascddar disease(ICVD),and the effects intensity of different risk factors on CAS.Methods Carotid intima-media thickness(IMT)was measured by color Doppler uhrasonography in 840 patients with ICVD,including cerebral infarction(ci),transient ischemic attack and insufficient blood-supply of vertebral-basilar artery.According to the results of uhrasonography,the patients were divided into four groups:normal(IMT≤0.9 mm),arterial sclerosis (0.9 mm1.5 mm)and stenosis(stenosis of lumina≥30%).The plasma fibrinogen and other biochemical markers were also detected.The history of hypertension,diabetes,hyperlipemia,smoking,drinking were recorded,and the blood pressure was measured.Results The level of fibrinogen was the highest((3.91±1.05)g/L)in the patients with CI,the difference was significant compared to the patients with TIA((3.45±0.81)S/L,X2=62.812,P<0.01),and so was the prevalence of CAS(77.0%),there was significant difference compared to the patients with TIA(61.8%,X2=9.000,P<0.01).The rate of CAS increased gradually with the quartiles of the fibrinogen(the odds ratios in the 2nd,3rd and 4th quartiles(3.16-3.72 g/L,3.72-4.39 g/L and>4.39 g/L)were 1.80,3.36 and 3.38 respectively,all P≤0.01).There were significant differences of age,fibrinogen,systolic blood pressure,hyperglycaemia and history of diabetes and hypertension between the normal-carotid group and three CAS groups.Multiple logistic regression showed that only the age,fibrinogen and systolic blood pressure significandy influenced on the CAS with the highest risk factor being the fibrinogen.Conclusions In the patients with ICVD,the elevated plasma fibrinogen Was significantly correlated with CAS,and misht play more important role than other traditional risk factors.

Objective To investigate the relationships between Glucokinase(GCK) gene 4 tag single‐nucleotide polymorphisms , tagSNPs)sites which named rs12702070 ,rs2268569 ,rs2268573 and rs1476891 polymorphisms and type 2 diabetes in Chinese South‐ern Han Population .Methods This study was designed as a case‐control .499 type 2 diabetes patients and 499 healthy controls were chosen .4 GCK tagSNPs sites were analyzed by improved multiple ligase detection reaction(iMLDR) ,and genotype and allele fre‐quency between T2D group and healthy controls could be determined by chi‐square test ,logistic regression analysis ,and tagSNPs were further analyzed under three genetic modes(dominant ,recessive and additive) .What′s more ,Haploview software was used to construct the haplotype of 4 GCK tagSNPs and the linkage disequilibrium(LD) and relationship between various GCK haplotype and T2D susceptibility could be analyzed .Results Genotype distribution of rs2268573 ,rs2268569 and rs1476891 and allele frequen‐cy in T2D group were no significant differences with health controls .Significant differences in genotype distribution of rs12702070 and allele frequency were observed between T2D group and health controls .Under dominant model and additive model ,genotype distribution of rs12702070 in T2D was significantly different from health controls .One LD domain was observed in 3 tagSNPs a‐mong those 4 sites of GCK gene .There are 4 main haplotypes(TAG ,TGG ,TAT ,CGG)in rs2268569 ,rs12702070 and rs1476891 , but all these haplotypes have no relevance to the individual risk of T2D(P>0 .05) .Conclusion The results indicated that the GCK gene tagSNPs site rs12702070 imparts susceptibility to T2D in Han Chinese ,but not rs2268573 ,rs2268569 and rs1476891 .Four main haplotypes in rs2268569 ,rs12702070 and rs1476891 have no relevance to T2D .

Objective To investigate the relationships between Glucokinase (GCK) gene 6 (tag single-nucleotide polymorphisms,tagSNPs)sites which named rs12702070,rs2971672,rs2268569,rs2268573,rs2300587 and rs1476891 polymorphisms and type 2 diabetes in Chinese Southern Han Population.Methods This study was designed as a case-control.499 type 2 diabetes patients and 499 healthy controls were chosen.All subjects were from August 2013 to December 2014 in Zhongshan Affiliated Hospital of Sun Yat-sen University.6 GCK tagSNPs sites were analyzed by improved multiple ligase detection reaction (iMLDR),and genotype and allele frequency between T2D group and healthy controls could be determined by chi-square test,logistic regression analysis,and tagSNPs were further analyzed under three genetic modes(dominant,recessive and additive).What's more,Haploview software was used to construct the haplotype of 6 GCK tagSNPs and the linkage disequilibrium (LD) and relationship between various GCK haplotype and T2D susceptibility could be analyzed.Results Genotype distribution of rs2268573,rs2300587,rs2268569 and rs1476891 (x2 were 3.361,2.076,0.582 and 0.918 respectively,all P ＞0.05) and allele frequency (x2 were 0.222,1.980,0.590 and 0.851 respectively,all P ＞ 0.05) in T2D group were no significant differences with health controls.Significant differences in genotype distribution of rs2971672 and rs12702070 (x2 were 6.896 and 7.990 respectively,all P ＜ 0.01) and allele frequency (x2 were 4.708 and 5.979,P ＜ 0.05 and P ＜ 0.01 respectively) were observed between T2D group and health controls.Under dominant model (rs2971672:OR =1.74,95％ CI =1.17-2.57,P ＜ 0.01;rs12702070:OR =1.54,95 ％ CI =1.17-2.04,P ＜ 0.01) and additive model (rs2971672:OR =1.51,95 ％ CI =1.06-2.14,P ＜ 0.05;rs12702070:OR =1.26,95％ CI =1.04-1.52,P ＜ 0.05),Genotype distribution of rs2971672 and rs2971672 in T2D were significantly different from health controls.There are two LD domains in 5 tagSNPs among those 6 sites of GCK gene.There are three main haplotypes(TC,TA,CA)in rs2971672 and rs2300587,and four main haplotypes (TAG,TGG,TAT,CGG) in Rs2268569,rs12702070 and rs1476891.Although TAG,TGG,TAT and CGG have no relevance to the individual risk of T2D (P ＞ 0.05),haplotype TA and CA reduce the individual risk of T2D with OR 0.81 (95％ CI:0.66-1.00,P＜0.05) and0.78 (95％ CI:0.62-0.98,P ＜0.01)respectively.Conclusions The results indicated that GCK gene 2 tagSNPs sites included rs2971672 and rs12702070 imparts susceptibility to T2D in Han Chinese,but not rs2268573,rs2300587,rs2268569 and rs1476891.Haplotype TA and CA in rs2971672 and rs2300587 reduce the individual risk of T2D and four main haplotypes (TAG,TGG,TAT,CGG) in rs2268569,rs12702070 and rs1476891 have no relevance to T2D.

Objective To investigate the relationships between glucokinase(GCK) gene 3 tag single‐nucleotide polymorphisms (tagSNPs)sites rs2971672 ,rs2268573 and rs2300587 polymorphisms with type 2 diabetes (T2DM ) .Methods A total of 499 south‐ern Han inpatients with T2DM (T2DM group) in our hospital and contemporaneous 499 Han individuals undergoing the physical examination(control group) in the Health and Fitness Protection Center of our hospital from August 2013 to December 2014 were chosen .The GCK gene 3 tagSNPs sites in all subjects were genotyped by adopting the improved multiple ligase detection reaction (iMLDR) ,and the genotype and allele frequency between the T2DM group and healthy controls were compared by the chi‐square test ,logistic regression analysis ,moreover the tagSNPs sites were performed the correlation analysis under three genetic modes (dominant ,recessive and additive) .The Haploview software was used to construct the haplotype of GCK gene 3 tagSNPs and the linkage disequilibrium(LD) and relationship between various GCK haplotype and T2DM susceptibility was analyzed .Results The differences of rs2268573 and rs2300587 genotypes(χ2 =3 .361 ,2 .076 ,P>0 .05) and allele frequency(χ2 =0 .222 ,1 .980 ,P>0 .05) between the T2DM group and the control group were not statistically significant .The difference of rs2971672 genotype(χ2 =6 .896 , P<0 .01) and allele distribution(χ2 =4 .708 ,P<0 .05) between the T2DM group and the control group was statistically signifi‐cant .Under the dominant genetic model and additive genetic model ,the genotype distribution of rs2971672 between the T2DM group and the control group was statistically significant(OR= 1 .74 ,95% CI:1 .17 -2 .57 ,P<0 .01 ;OR=1 .51 ,95% CI:1 .06-2 .14 ,P<0 .05) .Among 3 GCK gene sites ,rs2971672 and rs2300587 had the LD domain including 3 main haplotypes of TC ,TA and CA3 ,the TA and CA haplotypes all decreased the risk suffering from T2DM(OR=0 .81 ,95% CI:0 .66-1 .00 ,P<0 .05 ;OR=0 .78 ,95% CI:0 .62-0 .98 ,P<0 .05) .Conclusion In Han population ,GCK gene rs2971672 site is closely related with T2DM ge‐netic susceptibility ,while rs2268573 and rs2300587 sites have no obvious correlation with T2DM susceptibility .Haplotype TA and CA in rs2971672 and rs2300587 LD domain all reduce the individual risk suffering from T2DM .

OBJECTIVE:To determine serum concentrations of western medicines in patients treated with "traditional Chinese antiepileptic medicine" alone and to evaluate the curative effects.METHODS:A total of 60 epileptic patients who visited our hospital between Feb.1997 and June 2006 were subjected to plasma drug level monitoring and during which the patients were treated with "traditional Chinese antiepileptic drugs" alone.Plasma concentrations of 4 kinds of western medicin-es were determined by FPIA.RESULTS:Of the 60 cases,valproic acid,carbamazepine,phenytoin and phenobarbitone were detected in 18,40,41,and 47 cases/times,respectively.On average,more than two kinds of western medicines were detected in every patient,and the blood concentrations were mostly beyond effective plasma drug concentration.The total curative effects were unsatisfactory.CONCLUSION:The fact that western medicine ingredients detected in these traditional Chinese antiepileptic medicines is inconformity with medication principle of epilepsy.Traditional Chinese antiepileptic medicines should be used with caution in the clinic in the treatment of epileptic patients.

Objective To investigate the efficacy of endoscopy for the treatment of benign biliary stricture after biliary surgery.Methods The clinical data of 127 patients with benign biliary stricture after biliary surgery at the First Hospital of Lanzhou University from January 2007 to December 2011 were retrospectively analyzed.According to the Bismuth classification,there were 60 patients with type Ⅰ,35 with type Ⅱ,21 with type Ⅲ and 11 with type Ⅳ.The efficacies of endoscopy for the treatment of biliary stricture with different Bismuth subtypes were analyzed.Results The location and severity of biliary stricture were confirmed by endoscopic retrograde cholangiopancreatography (ERCP) + cholangiography.Sixteen patients ( including 7 with type Ⅲ and 9 with type Ⅳ) were transferred to surgical treatment due to severe biliary stricture.A total of 111 patients underwent endoscopic treatment successfully,with the success rate of 87.4％ (111/127).The success rates of endoscopy for the treatment of patients with Bismuth Ⅰ,Ⅱ,Ⅲ and Ⅳ biliary strictures were 95％ (57/60),86％ (30/35),9/14and 1/2,respectively.Twenty-nine patients were implanted with retrievable metallic biliary stent,and 82 were implantated with plastic biliary stent.Of the 111 patients,only 6 patients were complicated by acute pancreatitis,and they were cured by conservative treatment.The alleviative rates of yellow skin and icteric sclera,tenderness and distending pain of right upper quadrant,fever were 73％ (81/111 ),83％ (74/89),90％ (73/81 ) and 89％(68/76) at 1 week after treatment,and they were 88％ (98/111),91％ (81/89),94％ (76/81) and 92％(70/76) at 8 weeks after treatment.The efficacy of endoscopy was good in 97 patients and poor in 14 patients,and the 14 patients were converted to open surgery.The symptoms including yellow skin and icteric sclera,tenderness and distending pain of right upper quadrant,fever were completely alleviated at postoperative month 6.Conclusion Endoscopic treatment for benign biliary stricture is safe and effective.