Objective Platelet activating factor(PAF),which has been implicated in the pathophysiology of inflammation in asthma,is degraded and inactivated by PAF acetlhydrolase(PAF AH).To investigate the association of PAF AH activity with genotype in asthmatic children.Methods We studied 57 asthmatic children and 30 normal controls. The plasma PAF AH genotype was detected as representative case with 3 different genotypes (Val/Val,Val/Phe and Phe/Phe) by allele specific polymerase chain reaction(AS PCR).The PAF AH activity in plasam was examined by the changes of substrate assay.Results In severe asthmatic individuals plasma PAF AH activities were lower than those of mild or moderate groups and control group,and plasma PAF AH activition was absent 15.4 %.In another three groups plasma PAF AH activation were absent 2 %-3 %.There was significant difference of plasma PAF AH activity among 3 groups of genotype(Val/Val,Val/Phe and Phe/Phe).In the similar genotype, there was no significant difference of plasma PAF AH activity between the groups of control and asthma.Conclusions There was imbalace of PAF/PAF AH in asthmatic children. In severe asthmatic individuals plasma PAF AH activities were lower than those of mild or moderate groups and control group. PAF AH(Val279Phe) gene mutation was related with plasma PAF AH activity.

Objective To investigate the bid gene expression and cell death in brain after cerebral hypoxia-ischemia in neonatal rats and the effects of dexamethasone(DEX)on bid gene expression,so as to elucidate the possible mechanism of the neuroprotective effect of DEX pretreatment on rats following cerebral hypoxia-ischemia.Methods Twenty-four SD neonatal rats were divided randomly into hypoxia-ischemia brain damage(HIBD),normal,dexamethasone-pretreated and 9 g/L NaCl(NS)control group.The animal models of HIBD were made.Total RNA from ipsilateral cerebral hemisphere was extracted.Reverse transcription polymerase chain reaction(RT-PCR)was used to evaluate the level of bid gene expression after hypoxia-ischemia.Cerebral apoptosis was determined by terminal-deoxynucleotidy transferase mediated d-UTP nick end labeling(TUNEL).Results The levels of bid mRNA were higher in HIBD rats than those in normal rats.The number of positive apoptosis cells significantly increased in HIBD group(P

Objective To explore the cellular inhibitor of apoptosis protein 1(cIAP1)gene expression and Caspase-3 activity in brain after cerebral hypoxia-ischemia in neonatal rats and the influence of dexamethasone(DEX)on cIAP1 gene expression and Caspase-3 activity,so as to elucidate the possible mechanism of the neuro-protective effect of DEX pretreatment on rats following cerebral hypoxia-ischemia.Methods Twenty-four SD neonatal rats were divided randomly into hypoxic-ischemic brain damage group(HIBD group),normal group(NS group),dexamethasone-pretreated group(DEX group)and 9 g/L NaCl control group(NS group).The animal models of HIBD were made.Total RNA from ipsilateral cerebral hemisphere was extracted.Reverse transcription polymerase chain reaction(RT-PCR)was used to evaluate the level of cIAP1 gene expression after hypoxia-ischemia.Caspase-3 relative activity of brain tissue was determined by colorimetric assay.Results The levels of cIAP1 mRNA were lower in HIBD group than those in NS group.Caspase-3 relative activity significantly increased in HIBD group(P

Objective To evaluate the blood supply features and effectiveness of arterial chemoembolization for pedunculated hepatocellular carcinoma.Methods Angiography and chemoembolization via supplying blood arteries of tumor were performed in five patients with pedunculated hepatocellular carcinoma.Interventional procedure was carried out with tumor vascular infusion of 350 mg hot elemene emulsion and tumor embolization by cisplantin-lipidol emulsion(cisplantin 60-80 mg+lipidol 8-15 ml)and glutin.Results Ten interventional procedures(TACE)were undertaken in 5 patients.Angiography showed that tumor blood supply mainly coming from collateral circulation adjacent to the tumors,but partially from hepatic artery.Tumor sizes decreased from 30% to 50% in 5 cases,and AFP declined in 4 cases after the treatment. Conclusion Pedunculated hepatocellular carcinoma possessing different blood supply features from intrahepatocellular carcinomas.But transarterial ehemoembolization is still an effective method of choice for this treatment.

Objective To evaluate the effects of 131 adrenoceptor anfisense on blood pressure and?1 adrenoceptor mRNA and protein levels in 2 kidney 1 clip(2K1C)rats.Method 2KIC hypertensive rots were produced by clipping renal artery of SD rats.Liposome/AS-ODNs 2.0 were tested intravenously in rats with 2KIC hypertension.Animals were divided into 5 groups(n=18 in each group):?1-AS-ODN group,?1-IN-ODN group,2K1C group,Sham group and SD group.Blood pressure was measured by tail-cuff method,the levels of myocardial?adreneceptor mRNA and protein were tested by RT-PCR and binding assay.Results On the basis of the magnitude and duration of hypotension,?1-AS-ODN decreased blood pressure by 39 mmHg at the most for 4 weeks.Compared with the 2KIC group,?1-AS-ODN did not significantly change the levels of myocardial?1 adrenoceptor mRNA but significantly decreased the levels of myocardial?1 adrenoceptor protein at 2,7,30 days (P

Pancreatic cancer is a kind of highly malignant tumor with a low survival rate and poor prognosis. The effectiveness of gemcitabine as a first-line chemotherapy drug is limited; however, it can activate dendritic cells and improve antigen presentation which increase the sensitivity of tumor cell to immunotherapy. Although immunotherapy has made some advancements in cancer treatment, the therapeutic benefit of programmed cell death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) blockade therapy remains relatively low. The chemokine C-X-C chemokine ligand 12 (CXCL12) contributes to an immunosuppressive tumor microenvironment by recruiting immunosuppressive cells. The receptor C-X-C motif chemokine receptor 4 (CXCR4), highly expressed in various tumors including pancreatic cancer, plays a crucial role in tumor development and progression. In this study, the anti-tumor immune response of human peripheral blood mononuclear cell (hPBMC) was enhanced using the combination of BsNb PX4 (anti-PD-L1&CXCR4 bispecific nanobody) and gemcitabine. In a co-culture system of gemcitabine-pretreated hPBMCs with tumor cells, the BsNb PX4 synergized gemcitabine to improve the cytotoxic activity of hPBMCs against tumor cells. Flow cytometry analysis confirmed increased ratio of CD8⁺ to CD4⁺ T cells in combination treatment. In NOD/SCID mice bearing pancreatic cancer, the combination treatment exhibited more infiltration of CD8⁺ T cells into tumor tissues, contributing to an effective anti-tumor response. This study presents potential new therapies for the treatment of pancreatic cancer. Ethical approval was obtained for collection of hPBMC samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University (authorizing number: A2024246).

Objective To discuss the risks of hypertension development with relation to the level of lipid variables among populations who had normal blood pressure at baseline study. Methods In April 2000, under the support of project "prevention of metabolic syndrome and multi-metabolic disorders in Jiangsu province", a cohort study was performed to obtain the baseline data among 8685 persons from age 34 to 74. In June of 2006, a follow-up investigation was carried out among those who had been in the study for 5 years after the baseline study started. 2603 persons who met the selection criteria and showed normal blood pressure during baseline study, were recruited in this investigation. The interval from the baseline to the follow-up studies was 6.38 years on average. Relationship between the risk of developing hypertension and the baseline level of lipid variables were analyzed. Results Relations between baseline lipid levels and the incidence of hypertension during the follow-up was discovered. In gender and age adjusted model, the lipid variables were all associated with hypertension(Wend test, P<0.01). In multivariable-adjusted model, HDL-C [aRR=0.71 (95%CI: 0.61-0.99)], non-HDL-C [αRR=1.28 (95%CI: 1.14-1.83)], TC/HDL-C ratio[aRR=1.41 (95%CI: 1.25-2.03)] and TG [αRR=1.49(95%CI: 1.30-2.13)] were again associated with hypertension (trend test, P<0.05). Even the αRR was much weakened after the baseline SBP, DBP were adjusted with Cox model, the significant relation of hypertension to HDL-C, TC/HDL-C ratio and TG still existed. Excluding the two factors of obesity (BMI≥28) and diabetes which had been recognized in marked linking with hypertension, lipid variables were still associated with hypertension. Conclusion Dyslipidemia might occur before being hypertensive. Hypertension was associated with HDL-C, TC/HDL-C and TG or even exclusion of obesity, diabetes and factors of smoking and drinking or baseline level of SBP, DBP were adjusted.

OBJECTIVETo investigate the relative contribution of lifestyle and obesity to the risk of developing type 2 diabetes.

METHODSAll baseline survey data were based on the program Prevention of Multiple Metabolic Disorders and Metabolic Syndrome in Jiangsu Province (PMMJS) which was conducted during April 1999 to May 2004. In the baseline survey, 8685 participants were selected using multi-stage sampling method. Frem March 2006 to November 2007, 4582 participants who had been in the study for at least 5 years were included in the follow-up survey. A total of 3847 participants were followed and of them 3461 non-diabetic subjects were included in this analysis. High fat diet or not, low fiber diet or not, sedentary or not and occupational physical activity classification were defined as lifestyle variables and the incidence of type 2 diabetes at follow-up survey was defined as outcome variable. It was prospectively examined that the separate and joint association of lifestyle and obesity with the development of type 2 diabetes in subjects recruited from PMMJS, using logistic regression model.

RESULTSA total of 162 incident cases of type 2 diabetes during 6.3 years of follow-up in total 3461 participants were documented. The incidence rate was 4.7%. After adjusted for sex, age, family history of diabetes, blood pressure, lipids and fast plasma glucose, risk of type 2 diabetes increased with lighter occupational physical activity (compared with vigorous group, moderate group aRR = 2.15, 95%CI: 1.26 - 3.68; light group aRR = 2.39, 95%CI: 1.12 - 4.87), sedentary lifestyle (aRR = 2.94, 95%CI: 1.90 - 4.54), low fiber diet (aRR = 1.58, 95%CI: 1.01 - 2.53), overweight (aRR = 1.33, 95%CI: 1.01 - 1.90) and obesity (aRR = 1.59, 95%CI: 1.07 - 3.75). In joint analysis of lifestyle and obesity, the impact of sedentary lifestyle (in BMI < 25 group, aRR = 3.42, 95%CI: 1.99 - 5.86; in BMI ≥ 25 group, aRR = 2.41, 95%CI: 1.13 - 5.12) and low fiber diet (in BMI < 25 group, aRR = 1.42, 95%CI: 0.81 - 2.54; in BMI ≥ 25 group, aRR = 2.63, 95%CI: 1.15 - 6.03) on diabetes were independent of overweight and obesity. When stratified by sedentary lifestyle or low fiber diet, there was no association between overweight/obesity and diabetes risk (sedentary aRR = 2.04, 95%CI 0.87 - 4.71, non sedentary aRR = 1.21, 95%CI: 0.82 - 1.78; non low fiber diet aRR = 1.26, 95%CI: 0.87 - 1.84, low fiber diet aRR = 1.88, 95%CI: 0.80 - 4.80).

CONCLUSIONUnhealthy lifestyle, overweight and obesity independently increase the risk of type 2 diabetes. The magnitude of risk contributed by sedentary lifestyle and low fiber diet are much greater than that imparted by overweight and obesity.

Adult ; Aged ; Body Mass Index ; China ; epidemiology ; Diabetes Mellitus, Type 2 ; epidemiology ; Female ; Humans ; Life Style ; Male ; Middle Aged ; Obesity ; epidemiology ; Overweight ; epidemiology ; Risk Factors ; Sedentary Lifestyle

Objective To study the impact on dynamic change of waist circumference(WC) through follow-up data on the incidence of hypertension in several cohort groups.Methods In this prospective study,2778 free-hypertension subjects were recruited from a program “Prevention of Multiple Metabolic disorders and metabolic syndrome (MS) in Jiangsu province” (PMMJS) to evaluate the risk of hypertension in relation to WC dynamic change on normal WC or abnorminal obesity group.Dynamic change of WC was measured by WC D-value,which was expressed by data on the difference of WC between baseline and the first follow up.Study outcome was defined as incident hypertension during the first to the second follow up period in this study.The association between dynamic change of WC and incident hypertension was analyzed by using Cox proportional hazards regression model.Results There were 2778 participants,660 subjects developed hypertension during the follow-up,regardless of the normality of the baseline WC,the risk of hypertension increased across the tertiles of WC,while the incidence of hypertension was higher in non-control group than that in control group.In populations with abdominal obesity and normal WC at baseline,RRs (95％CI) of hypertension were 1.95 (1.19-3.19) and 2.38 (1.89-2.99) in subjects with abdominal obesity seen at the first follow up period,compared to subjects with normal WC in the same period.After adjustment for gender,age and other hypertension related risk factors,in populations with abdominal obesity and normal WC at baseline survey,RRs (95％ CI) of hypertension were 4.36 (1.69-9.74) and 1.44( 1.03-2.35 ) respectively,for the non-control group.Conclusion WC dynamic change was associated with hypertension,WC control while WC reduction was important for early prevention on hypertension.

Objective To investigate the association between ten single nucleotide polymorphism (SNP) in the peroxisome proliferator-aetivated receptor (PPAR) α/δ/γ and essential hypertension (EH).Methods Participants were recruited within the framework of a cohort populations survey from the PMMJS (Prevention of Multiple Metabolic Disorders and MS in Jiangsu Province) which was conducted in the urban community of Jiangsu province from 1999 to 2007.Eight handred and twenty subjects (551 non-hypertensive subjects,269 hypertensive subjects) were randomly selected but were not related to each other.Ten SN P ( rs 135539,rs1800206,rs4253778 of PPAR αt; rs2016520,rs9794 of PPARδ ; rs10865710,rs1805192,rs4684847,rs709158 and rs3856806 of PPARγ ) were selected from the HapMap database.x2 test was used to determine whether the whole population was in H-W genetic equilibrium.SHEsis software was used to examine the relations of SNP and linkage equilibrium.Logistic regression model was used to examine the association between ten SNP in the PPAR and EH.Results Difference on the distribution of four SNP genotypes including rs1800206,rs9794,rsl0865710 and rs4684847 between high blood pressure and non-high blood pressure group,high systolic blood pressure(SBP) and normal SBP group,high diastolic blood pressure(DBP) and normal DBP group was significant (P＜0.05).After adjusting factors as age,sex,body mass index,fasting plasma glucose,high density lipoprotein cholesterol-C,high-fat diet and compared with wildtype gene carriers,the OR(95％ CI) of objects with rs1800206 V allele appeared in high blood pressure,high SBP and high DBP were 0.60 (0A1-0.89),0.57 (0.37-0.88) and 0.61 (0.39-0.96),respectively.The OR(95％CI) of objects with G allele of rs9794 were 0.63 (0.46-0.87),0.51 (0.36-0.73) and 0.68(0.47-1.01).The OR (95％CI) of objects with G allele of rs10865710 were 1.62 (1.19-2.20),1.59(1.14-2.22) and 1.53 ( 1.07-2.18),respectively.While the OR (95％ CI) of objects with rs4684847 T allele were 1.42 ( 1.04-1.94),1.38 (1.03-1.92) and 1.37 ( 1.00-1.88),respectively.Conclusion The four SNPs including rs1800206 of PPARα,rs9794 of PPARδ and rs4684847,rs10865710 of PPARγ influenced high blood pressure,high SBP and high DBP to different degrees.