The gamma-secretase complex mediates the final cleavage of APP to generate the principal component of amyloid plaques in the brains of Alzheimer's disease patients.Four integral membrane proteins (PS,NCT,PEN-2 and APH-1) are essential and sufficient for gamma-secretase activity.To identify the promoter of human nicastrin gene (NCT),its 5' -flanking region has been characterized and a 270 bp fragment containing the TSS (transcription start site) for the promoter activity has been identified.EMSA assays confirmed that all four AP-1 binding sites and two NFAT sites in the NCT promoter region were able to bind relative transcription factors in vitro.Mutations,as well as treatment with PDTC,which adjust the regulatory effect of AP-1 and NFAT,altered NCT promoter activity in both HeLa cells and rat cortical neurons.The results demonstrated that AP-1 and NFAT are involved in the regulation of hNCT transcription and suggest that balanced activation of AP-1 and NFAT ensures a strict temporal and tissue-specific control of NCT transcription.

OBJECTIVETo evaluate the effects of prenatal stress on neurological functions after middle cerebral artery occlusion (MCAO) in adult offspring rats.

METHODSPregnant rats were randomly assigned to prenatal stress treatment, which was exposed to restraint three times daily in the last week of pregnancy, and no prenatal stress treatment. Adult male offspring rats were subjected to transient focal cerebral ischemia by MCAO. They were randomly divided into four groups: sham group, prenatal stress + sham group, MCAO group and prenatal stress + MCAO group (n = 10). After 24 hours of reperfusion, the neurological deficits were evaluated. The infarct size, cell apoptosis and expression of Caspase 3, cleaved Caspase 3 and Bcl-2 were detected.

RESULTSCompared with MCAO group, the neurological deficits, infarct size and apoptotic cells in prenatal stress + MCAO group were increased significantly (all P < 0.05). The expressions of Caspase 3 and cleaved Caspase 3 were much greater in prenatal stress + MCAO group than those of MCAO group, while the expression of Bcl-2 was significantly decreased in prenatal stress + MCAO group compared with MCAO group (all P < 0.05).

CONCLUSIONPrenatal stress might exacerbate neuroloeical deficits in the offspring rats after MCAO by increasing cell apoptosis.

Animals ; Apoptosis ; Caspase 3 ; metabolism ; Female ; Infarction, Middle Cerebral Artery ; physiopathology ; Ischemic Attack, Transient ; physiopathology ; Male ; Pregnancy ; Prenatal Exposure Delayed Effects ; physiopathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Stress, Physiological

OBJECTIVE:To evaluate the availability and equipment of antidiabetic drugs in public hospitals from Shaanxi prov-ince. METHODS:Using a standardized methodology developed by WHO and Health Action International,the availability and equipping rate of the most common oral antidiabitic drugs were investigated and evaluated in public hospitals of Shaanxi province. RESULTS:The availability and equipping rate of tertiary hospitals and secondary hospitals were all higher than those of community health service centers. Among generic drugs,the availability of metformin was the highest (94.4%),and those of glibenclamide and repaglinide were the lowest(5.6%). Among original drugs,the availability of acarbose was the highest(68.1%). The equip-ping rate of original drugs was higher than that of generic drugs. The equipping rate of generic drugs(25.0%)was higher than that of original drugs(12.5%)in community health service center,but the equipping rates of generic drugs and original drugs were in low level. CONCLUSIONS:General hospitals (especially tertiary hospitals) have high equipping rate of original antidiabetic drugs,the community health services have low availability and equipping rate. Comprehensive measures should be taken to im-prove the availability of drugs in primary medical institutions and ensure drug use of chronic disease patients in primary hospitals.

Objective To investigate the feasibility of iterative model reconstruction (IMR) combined with low tube voltage and low iodine intaken of contrast media in head and neck CT angiography (CTA). Methods Eighty patients with clinical suspicion of head and neck vascular disease underwent head and neck CTA were enrolled in this prospective study. According to random number table, patients were randomly divided into two groups. Group A (n=40) was scanned according to the protocol of 120 kV, 50 ml iopromide (370 mg/ml) and filtered back projection (FBP) reconstruction, and group B (n=40) was scanned with 80 kV, 30 ml iohexol (300 mg/ml) and IMR, while the other parameters kept consistent. Mann-Whitney U test was used to compare the enhanced CT value of arteries, image noise, signal noise ratio (SNR), contrast noise ratio (CNR), the score of image quality, effective radiation dose (ED) and iodine intaken of contrast media between two groups. Results The CT value at the origin level of common carotid artery were (316.9 ± 53.0) and (433.4 ± 101.8)HU in group A and B, image noise were (28.1 ± 6.8)and (12.1 ± 2.6)HU ,SNR were (11.9 ± 3.2) and (37.7 ± 13.3) ,and CNR were (10.2 ± 2.9) and (32.6 ± 13.3), respectively. There were showed significant differences in CT value, image noise, SNR and CNR between two groups (Z=-5.490,-7.592,-7.698,-7.660, P<0.05). The CT value at the origin level of internal carotid artery were (359.5 ± 54.3) and (443.5 ± 120.1) HU in group A and B, image noise were (18.8±6.2) and (6.8±1.7) HU ,SNR were 21.5±8.7 and 69.7±27.4 ,and CNR were 18.0±7.3 and 62.7± 26.4, respectively. The significant differences were acquired in CT value, image noise, SNR and CNR between two groups (Z=-3.022,-7.376,-7.496,-7.515, P<0.05). The CT value at M1 segment level of middle cerebral artery were (321.1±47.3) and (401.6±104.0) HU in group A and B, image noise were (32.3± 17.2) and (11.2 ± 2.7) HU,SNR were 12.4 ± 5.6 and 39.3 ± 18.4,and CNR were 10.7 ± 4.7 and 36.4 ± 17.7, respectively. There also showed significant differences in CT value, image noise, SNR and CNR between two groups (Z=-3.527,-7.487,-7.482,-7.535, P<0.05). The score of image quality of group A and B were 3.9 ± 0.7 and 4.5±0.6, which also showed significant difference between two two groups (Z=-3.517, P<0.05). The ED were (2.78 ± 0.13) and (0.84 ± 0.04) mSv for group A and B, which also showed significant difference between the two groups (Z=-7.706, P<0.05). The iodine intaken of contrast media were 1.85 g and 0.90 g in group A and B. Conclusion IMR combined with low tube voltage and low iodine intaken of contrast media can not only decrease effective radiation dose and iodine intaken of contrast media significantly, but also improve the imaging quality in head and neck CTA examination.

The specific fragment of Pneumococcal surface protein A(PspA)and Pneumococcal Surface Adhesin A(PsaA)gene was amplified by PCR from Streptococcus pneumonia 5 and Streptococcus pneumonia 19.The amplified fragnent of PspA and PsaA gene was ligated into pET-27b(+)vector and transformed into BL 21 E.coli for expression and obtain the expressive production of PspA and PsaA.Induced by IPTG,the expression level was as high as 75 % of the total disolube protein.The result showed that the recombinant plasmid could express a specific 75 kDa and 37 kDa fusion protein in E.coli BL 21,which showed the good immunogenicity and a broadly cross reactivity with the other serotypes.

G mutation of SLC26A4, the parents and the second child were carriers of the same mutation, while the fetus had a wild-type form. Conclusion It is feasible to identify deafness related genes by screening for GJB2 and SLC26A4 mutation, thus providing correct prenatal diagnosis and avoiding deaf delivery of baby.

Objective To observe the clinical efficacy of Bai Xiao moxibustion plus electroacupuncture in treating lumbar intervertebral disc herniation (LIDH). Method Ninety-six LIDH patients were randomized into a treatment group and a control group, 48 cases each. The treatment group was intervened by Bai Xiao moxibustion plus electroacupuncture, while the control group was intervened by electroacupuncture alone. Before and after the treatment, the lower back pain scores of Japanese Orthopedic Association (JOA) and Visual Analogue Scale (VAS) were evaluated, and the clinical efficacies of the two groups were compared. Result The JOA and VAS lower back pain scores were changed significantly after the treatment in both groups (P<0.05). After the treatment, the JOA and VAS lower back pain scores of the treatment group were significantly different from those of the control group (P<0.05). The pain release time was (2.95±0.59)d after the intervention in the treatment group versus (4.26±0.68)d in the control group, and the between-group difference was statistically significant (P<0.05). The total effective rate was 95.7％ in the treatment group versus 91.7％ in the control group, and the between-group difference was statistically significant (P<0.05). Conclusion Bai Xiao moxibustion plus electroacupuncture is an effective method in treating LIDH and it can reduce the lower back pain.

Objective To investigate the incidence and the prognosis of acute kidney injury (AKI) and to find out the risk factors associated with the outcome for better understanding and preventing AKI among inpatients. Methods All the hospitalized patients were screened by Lab Administration Network of Renji Hospital,Shanghai Jiaotong University School of Medicine from Jan.to Dec.2009.Study cohort was comprised of all the patients with AKI defined by Acute Kidney Injury Network (AKIN) and with complete clinical data recorded.The incidence,etiology and distribution characteristics, prognosis of AKI in hospitalized patients were retrospectively analyzed.Logistic regression analysis was used to investigate the risk factors of patients and renal outcome. Results A total of 934 patients with AKI were enrolled.The incidence of AKI in hospitalized patients was 2.41％ (934/38 734).The ratio of male to female was 1.88∶1.Age was (60.82±16.94) years old.Increasing incidence could be seen with age rising.There was 63.4％ AKI found in surgical department,35.4％ in internal medicine department and 1.2％ in obstetric and gynecologic department.Pre-AKI,acute tubular necrosis (ATN),acute glomerular and renal vascular injury (AGV),acute interstitial nephritis (AIN) and post-AKI were accounted for 51.7％,37.7％,3.8％,3.5％ and 3.3％ of the causes of AKI,respectively.On day 28,the survival rate was 71.8％,complete renal recovery rate was 65.7％,partial renal recovery rate was 16.9％ and renal loss rate was 17.4％ among all the patients with AKI.The mortality of AKI with stage Ⅰ,Ⅱ and Ⅲ among inpatients was 24.8％,31.2％ and 43.7％ respectively.Multivariate Logistic regression analysis showed that renal injury drugs [odds ratio (OR)=2.313],hypotension (OR=4.482),oliguria (OR =5.267),the number of failure organs except kidney (OR =1.376) and requiring renal replacement therapy (RRT)(OR=4.221) were independent risk factors for death among AKI patients.The number of failure organs except kidney (OR=1.529) and RRT (OR=2.117) were independent risk factors for kidney loss. Conclusions AKI is one of the most common complications in hospitalized patients.The mortality is high and renal outcome is poor after AKI.The prognosis is closely associated with the severity of AKI.Renal injury drugs,hypotension,oliguria,the number of failure organs except kidney and requiring RRT are independent risk factors for death among AKI patients,while the number of failure organs except kidney and requiring RRT are independent risk.factors for renal loss.

Objective To investigate the expression of CD27-CD70 co-stimulatory pathway in peripheral circulation and intestinal mucosa of patients with inflammatory bowel disease, and to find the difference between the expression of CD27-CD70 in patients with inflammatory bowel disease and in healthy controls. Methods A total of 62 patients with Crohn's disease, 64 patients with ulcerative colitis and 56 healthy controls were enrolled. Enzyme-linked immunosorbent assay was applied to evaluate plasma CD27-CD70 protein expression in patients with inflammatory bowel disease and healthy controls. SYBR-green real time PCR was applied to access CD27-CD70 mRNA expression in peripheral blood mononuclear cells in patients with inflammatory bowel disease and healthy controls.And CD27-CD70 protein expression in intestinal mucosa was determined by immunohitochemistry.Results Plasma levels of CD27 (P=0. 025) and CD70 (P=0. 000) were significantly higher in patients with Crohn's disease than in healthy controls. However, CD27 (r= 0. 055, P= 0. 673) and CD70 (r= 0. 024, P = 0. 852) were not significantly associated with endoscopic disease activity in patients with Crohn's disease. Similarly, CD27 (P=0. 001) and CD70 (P=0. 000) were significantly higher in patients with ulcerative colitis than in healthy controls. And CD27 (r=0. 077, P=0. 547)and CDT0 (r=0.021, P=0. 869) were not significantly associated with endoscopic disease activity in patients with ulcerative colitis. Moreover, CD27 and CD70 mRNA expression in peripheral blood mononuclear cells were significantly higher in patients with Crohn's disease and ulcerative colitis than in healthy controls (all P=0. 000), and immunostaining indicated that CD27 and CD70 expression in intestinal mucosa were significantly higher in patients with Crohn's disease and ulcerative colitis than in healthy controls (all P=0. 000). Conclusions CD27-CD70 pathway activated in plasma, peripheral blood mononuclear cells and intestinal mucosa of patients with inflammatory bowel disease. However,plasma levels of CD27 and CD70 can not reflect endoscopic disease activity.

OBJECTIVESTo explore the changes of hepatic gene expression during the course of nonalcoholic fatty liver disease (NAFLD) development in rats.

METHODSA rat model of NAFLD was developed by feeding the animals a high-fat diet for 24 weeks. Liver tissues of the model rats and the control rats were analyzed at different time points using rat U230A (Affymetrix GeneChip), which covers 15650 genes.

RESULTSCompared with the control rats, the number of genes expressed differently in the model group rats at 4 and 8 weeks was 426 and 540. The up-regulated genes among them were intracellular phosphorylase genes, metabolic enzyme genes, fatty acid binding protein genes, cytochrome P450 genes, cellular transcription and differentiation genes. The down-regulated genes were ionic channel genes, hormone receptor genes, and cytoskeleton genes. At the 12th week, the number of the genes expressed differently was 501, in which 352 were up-regulated genes, including genes related to inflammation and apoptosis such as interleukin and Toll-like receptor 4. At the 16th week, the number of the differently expressed genes was 665, with 430 up-regulated, such as those related to the inflammation and apoptosis genes and collagen I and fibrosis genes, however cell regeneration genes were down-regulated. At the 24th week the number was 663, of which fibroblast growth factor, transforming growth factor and insulin-like growth factor genes were up-regulated. Of all the differently expressed genes, the number of up-regulated genes was 128, including 10 lipogenic genes, 46 metabolic genes, 15 inflammation genes, 10 apoptosis genes, and 16 fibrosis genes; and the down-regulated genes were 52, including 6 hormone receptor genes, 5 cell regeneration genes and 11 electron transport genes.

CONCLUSIONThe changes of the hepatic gene expression of rats fed a fat-rich diet are related to the duration of the feeding, and are correlated with their histopathology in the livers.

Animals ; Dietary Fats ; Fatty Liver ; etiology ; genetics ; Gene Expression Profiling ; Liver ; metabolism ; Oligonucleotide Array Sequence Analysis ; Rats ; Rats, Sprague-Dawley