Objective To explore the relationships between angiotensin converting enzyme (ACE) gene polymorphism of insertion/deletion(I/D) and cognition function in senile depressive patients in Chinese Han population.Methods 97 patients with major depression were recruited according to the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition criteria,and 103 healthy persons were used as controls.The Hamilton Depression Scale (HAMD) and neuropsychological tests were used to assess depressive severity and cognitive function in all patients and 44 healthy controls,respectively.The intron 16 I/D polymorphism of ACE gene was detected by polymerase chain reaction (PCR).Results The performances of neuropsychological tests in case group except TMT B were significantly poorer than those in control group (P＜ 0.001).Correlation analysis indicated that the total scores of HAMD were negatively associated with Digit Span Test forward score in senile depressive patients (r=-0.213,P=0.040).There were no significant differences between case and controls on genotype and allele frequencies of ACE gene(x-2 =1.745,P=0.418 ; x2 =0.700,P=0.403).And there were no significance in different sex,respectively (P ＞ 0.05).Furthermore,no significant differences of neuropsychological test performances were found between ACE genotypes of senile depressive patients (P ＞ 0.05).Conclusion Senile depressive patients have extensive cognitive impairments in the acute phase of illness,and working memory performance is correlated with depression severity.ACE gene Ⅰ/D polymorphism may not significantly associate with cognitive function in senile patients.

By analysing the new requirements of higher medical education curriculum in the new era,making curriculum changes of Nanjing Medical University as an analysed object,the arti-cle analyses the existing problems and shortcomings of China's current medical education course system,puts forward optimizing the course system further by running clear thinking,construction of composite course system,innovating teaching methods,strengthening the building of teaching mate-rials,the establishment of curriculum assessment mechanisms.

Objective To enrich pancreatic cancer stem cells through culturing mammospheres, and to detect the expressions of epidermal growth factor receptor(EGFR) and a disintegrin and metalloprotease 9 (ADAM9) and investigate their significance. Methods PANC1 cells were cultured in serum-free conditioned medium to continuously generate mammospheres, and parts of mammospheres were cultured on a collagen substratum to induce differentiation. Mammospheres cells and differentiated cells were collected, flow cytometry was used to detect the proportion of side population (SP) cells, and the expressions of EGFR, ADAM9 mRNA and protein were detected by real-time PCR and Western blotting. Results PANC1 cells mammospheres were successfully generated and could be passed continuously. After differentiation, mammospheres cells could regain the ability of adherent growth. The proportion SP cells in mammospheres cells and differentiated cells were ( 5.40 ± 0.38 ) % and (2.80 ± 0.42 ) %, and the difference was statistically significant ( P ＜ 0. 05 ).Compared with differentiated cells, the expression of EGFR and ADAM9 mRNA of mammospheres cells upregulated 2.5 and 3.0 folds ( P ＜ 0. 05 ). The expressions of EGFR and ADAM9 protein of mammospheres cells were 0.90 ± 0. 09 and 0.64 ± 0.07, which were significantly higher than those in differentiated cells (0.62 ±0.11 and 0.48 ±0.09, P ＜0.05). Conclusions Mammosphere cells contained higher proportion of pancreatic cancer stem cells. ADAM 9 may play an important role in the occurrence and development of pancreatic cancer through the EGFR signaling pathway.

A nitrite electrochemical sensor based on electrodeposition of zirconium dioxide nanoparticles on reduced graphene oxide modified electrode was successfully constructed for the detection of nitrite. The electrochemical behavior of the modified electrode was investigated by cyclic voltammetry and amperometric i-t curve. Under the optimal conditions, the amperometric i-t curve response of the electrode showed a linear relationship with nitrite concentration in the range of 3.0×10Symbolm_7-1.0×10Symbolm_6 mol/L and 1.0×10Symbolm_6-6.0×10Symbolm_6 mol/L, and the detection limit was 1.0×10Symbolm_7 mol/L (S/N=3). The fabricated sensor exhibited high sensitivity, good stability and high reproducibility. This sensor was applied for the detection of nitrite in sausage samples with favorable recoveries of 93.7％-110.4％ and relative standard deviation (RSD) of 1.6％-2.1％.

BACKGROUND:The laser applied in the clinical oral medicine is mainly for early diagnosis of caries, removal of carious tissue, pulpotomy for pulp bleeding, dentin hypersensitivity treatment, disinfection of infected root canals, and periodontitis treatment. OBJECTIVE:To explore the changes of basic fibroblast growth factor in inflammatory pulp after laser treatment. METHODS:Five healthy adult beagle dogs were enroled, and six teeth were randomly selected from each dog. Then, these teeth were randomly divided into three groups, 10 teeth in a group, and they were treated with laser irradiation, saline and gentamicin irrigation respectively. At days 1, 2, 3 after operation, exudates from the pulp were colected for detection of basic fibroblast growth factor expression. Meanwhile, the dental pulp was detected by hematoxylin-eosin staining and immunohistochemistry method. RESULTS AND CONCLUSION:In the al three groups, the expression of basic fibroblast growth factor at day 3 was significantly higher than that at days 1 and 2, and there were no differences between days 1 and 2. Moreover, these three groups also showed no significant differences. Under hematoxylin-eosin and immunohistochemical staining, blood vessels in the pulp cavity were in good condition and the pulp arranged tightly. These findings suggest that the laser is safe, convenient and effective for oral clinical application, and has no injury to the inflammatory pulp.

The purpose of this study was to investigate the pharmacokinetic interaction between sunitinib and ramipril in rats. Eighteen male SD rats were divided into three groups, with each group being assigned to orally receive sunitinib, ramipril, sunitinib and ramipril, respectively, for ten days. Blood samples were collected at dif-ferent times after first-day and tenth-day administration. The concentrations of ramiprilat and sunitinib in rat plasma were determined by LC/MS/MS and the pharmacokinetic parameters were calculated and statistically analyzed. Compared with the administration of ramipril alone, after a single-dose combined administration, tmax of ramiprilat decreased significantly and t1/2 prolonged, while AUC0-∞ remained unchanged. These results indicated that the ab-sorption rate of ramiprilat increased and the elimination rate decreased, but total absorption degree was not changed. After multiple-dose administrations, CL of ramiprilat decreased and AUC0-∞ increased obviously. It sug-gested that accumulation of ramiprilat occurred in body and the drug elimination became slower. No obvious difference of sunitinib pharmacokinetic behavior was found when it was given in combination with ramipril after a single-dose administration or multiple-dose administration. Sunitinib decreased the elimination of ramiprilat after co-administration in company with drug accumulation in body after multiple-dose co-administration. The study showed that there were pharmacokinetic interactions between sunitinib and ramipril in SD rats.

Objective To clone and express surface antigen SAG4 gene of Toxoplasma gondii, and analyze its immunoreactivity. Methods Specific primers were designed based on the reported SAG4 gene of T. gondii RH strain (GenBank Accession No: AF340224.1). Using genomic DNA from T. gondii as templates, SAG4 gene was amplified by PCR. The PCR product was cloned into pMD19-T vector and identified by digestion with restriction enzyme and PCR. Then the target fragment was subcloned into pET28a(+) vector, transformed into E. coli BL21 and followed by expression of the protein induced by IPTG. The protein was identified by Western blotting. Results The target gene was amplified with the length of 537 bp. Sequence analysis showed that the predicted amino acid sequence was identical with that of SAG4 as a membrane protein in T. gondii. After induced by IPTG, the recombinant SAG4 protein existed in an inclusion body form. The recombinant SAG4 (Mr 18 740) was recognized by serum of infected mice. Conclusion SAG4 has been expressed and shows certain immuno-response activity.

Objective To observe apoptotic cells and caspase-3-positive cells in ipsilateral neonatal hypoxic-isch?emia encephalopathy (NHIE) model in mice. Methods CD1 mice of age 7 days (n=30) were randomly divided into two groups: sham group (n=9) and model group (n=21). NHIE model was induced by right common carotid artery ligation fol?lowed by 8%oxygen hypoxia for 100 min. TTC staining was used to determine area of brain infarction. DAPI staining was used to detect pathological change in brains. TUNEL assay was used to detect apoptotic cells and fluorescence immunohisto?chemistry was used to detect caspase-3 expression in the ipsilateral brain. Results No infarct was detected in sham group. Cells were densely and orderly arranged in brain. TUNEL-positive cells (18.57±4.98) and caspase-3-positive cells (9.17± 2.14) in the ipsilateral brain were both less than those in the ipsilateral brain of mice in model group (209.57±41.27) and (63.33±16.22) respectively. Mice in model group presented infarct in the right hemisphere with more dead cells and wider in?terstitial space compared with sham group. Conclusion Brain injury in NHIE model might be related to the increasing cas?pase-3 expression thus leads to apoptosis.

AIM　This study was conducted to identify the human CYP isoforms responsible for the biotransformation of clivorine in human liver microsomes and the mechanism of metabolism-induced hepatotoxicity of clivorine. METHODS　Human liver microsomes were used to investigate the metabolism of clivorine in vitro. Selective CYP-450 inhibitors and cDNA expressed human CYPs were used to study their effects on the formation of hepatotoxic metabolites and the metabolism of clivorine and the principal CYP-450 isoform involved in the formation of hepatotoxic metabolite. RESULTS　Four metabolites, namely dehydroretronecine(DHR), 7-glutathionyl-dehydroretronecine(7-GSH-DHR), 7,9-diglutathionyl-dehydroretronecine(7,9-diGSH-DHR) and clivoric acid were found in the microsomal incubations. Chemical inhibition studies indicated that the metabolism of clivorine and the formation of pyrrolic metabolites as well as the bound pyrroles were strongly inhibited by CYP3A inhibitor ketoconazole(Ket). Whereas α-naphthoflavone(Nap), sulfaphenazole(Sulp), quinidine(Qui), diethyldithiocarbamate(DDC) have no significant effects on the metabolism of clivorine and the formation of pyrrolic metabolites in human liver microsomes. The results of metabolism of clivorine by cDNA expressed human CYPs showed that only CYP3A4 was found to be capable of catalyzing the metabolism of clivorine, while CYP1A2, CYP2C9, CYP2D6 and CYP2E1 did not play significant roles in the metabolism of clivorine and the formation of pyrrolic metabolites. CONCLUSION　The resultsdemonstrated that the pyrrolic metabolites were the major in vitro metabolites of clivorine and CYP3A4 was the major CYP isoform involved in clivorine metabolism and the formation of hepatotoxic pyrrolic metabolites in human liver microsomes. CYP3A4 plays a key role in the clivorine induced hepatotoxicity.

Objective To investigate the effect of xenon intervention on delayed neuropsychologic sequelae (DNS)in acute carbon monoxide(CO)poisoning.Method Adult Wistar rats were randomly divided into sustained group,early intervention group,and control group.CO(150 ml/kg)was infused by intraperitoneal injection to produce DNS model.In sustained intervention group(S-group),xenon(150 ml/kg/d)was infilsed by intraperitoneal injection for 2 weeks;in control group(C-group),xenon was replaced by equal volume air;and in early intervention group(E-tvoup),xenon(150 ml/kg/d)was,employed in the first 3 days and air(150 ml/kg/d)was substituted for xenon in the following days until 2 weeks after CO poisoning.Morris maze test was used to evaluate the intelligence of rats.The long-term potentiation(LTP)of hippocampus Was detected by neuroelectricity recording.The apoptosis rates in brain was detected by TUNEL staining.The data were expressed as(x±s)and analyzed with student's test and analysis of variance.A P value less than 0.05 indicated statisfical significance.Results After exposure to CO,poisoned rats showed intelligence decline,demyeliation ofwater matler and cell apoptosis increased,which were consistent with DNS.In S-group and E-group,the rates of DNS and apoptosis were significantly lower than those in C-group,whereas the rote of LTP in S-group and E-group Was significantly higher than those in C-group.Conclusions Early xenon intervention can effectively decrease the rates of DNS occurred after acute CO poisoning.