Objective To explore the feasibility of the applicatoin of readout-segmented echo-planar imaging (RS-EPI) at 3.0T MR of the orbit DWI and compared with single-shot echo-planar imaging (SS-EPI).Methods Forty-two volunteers underwent both standard SS-EPI and RS-EPI DWI of the orbit at a 3.0T MR unit.Two sets of DWI images were independently qualitatively scored in the number of distinguishable normal structures,fat suppression,ghosting artifact and overall image quality.SNR of the vitreous body,geometric distortion ratio (GDR) in both anterior-posterior (AP) and right-left (RL) direction,and ADC value of the vitreous body and pons were also quantitatively calculated and compared between two sets of DWI images.The statistical analysis was performed.Results For qualitative assessment,the RS-EPI was superior to SS-EPI on the number of distinguishable normal structures (P=0.009 0),ghosting artifact (P＜0.000 1),and overall image quality (P＜0.000 1),while no significant difference was found on fat suppression (P=0.753 9).For quantitative assessment,RS-EPI had significantly lower GDR than the SS-EPI in both AP and RL direction (P=0.001 4,0.001 7).The SNR in RS-EPI was significantly lower than that of SS-EPI (P=0.004 0).Meanwhile,there was no significant difference of ADC on vitreous body and pons between RS-EPI and SS-EPI (P=0.143 8,0.126 2).Conclusion The RS-EPI can provide better image quality than SS-EPI protocol in orbital DWI at 3.0T MR imaging.

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 analyse the etiology and clinical characteristics of 26 critically ill children with severe hand foot and mouth disease (HFMD) of Shanxi province in 2010.Methods We retrospectively analysed the clinical data of 26 children with severe HFMD from Mar to Sep 2010.Nucleic acid of enterovirus 71 ( EV71 ) and Coxsackie virus A 16 ( CoxA16) were detected in 20 out of 26 children with HFMD by reversed real time polymerase chain reaction (rRT-PCR),and the whole VP1 gene of EV71 deriving from 6 different areas of Shanxi province was amplified,sequenced,and compared with strains from other areas in china.Results EV71 nucleic acid were positive in 18 out of 20 children,while the other two were negative for EV71 and CoxAl6.Among all the critical cases,20 cases (76.9％) occurred in Weinan area,four in Xianyang area,and two in Xi'an urban area.Compared with those of Fuyang Anhui,Hong Kong China,Guangzhou,Shenzhen,Shandong,Beijing,the homology of the whole VP1 gene sequence from 6 strains of Shanxi area was 96％ ～ 100％.Most of the critical children were under 3-year-old,and the incidence rate of male children was higher than that of female children.All affected children had persisted fever,poor energy,hyperarousal,hypersomnia,and limb shaking.Meanwhile their peripheral blood leukocytes,C-reactive protein and blood glucose were markedly increased,but renal injuries were rare.Eighteen children clinically recovered on discharge,among which 2 cases had sequelae of limb activity obstacle,and 8 cases died.Conclusion Weinan is the area with the highest incidence rate of critical HFMD cases in Shanxi Province,and the major etiological organism is EV71,which is highly homologous to EV71 found in other regions of mainland China.As many cases are in dangerous condition,thus early identification and intervention could inhibit the disease progression,and play a key role in reducing the mortality.

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.

A high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for the determination of mizoribine in human serum using thiamphenicol as internal standard (IS). The serum samples of mizoribine were precipitated with acetonitrile and separated by HPLC on a reversed phase C18 column with a mobile phase of 0.1% ammonium acetate water solution-methanol (47:53, v/v). Mizoribine and IS were detected in the multiple reaction monitoring mode with precursor/product ion transitions of m/z 258.2/126.0 and 354.1/185.2, respectively. The calibration curves were linear over the range of 0.02-2 microg mL(-1) for mizoribine. The limit of quantification (LOQ) was 0.02 microg mL(-1) with acceptable precision and accuracy. The validated method was successfully applied for the evaluation of a bioequivalence study on Chinese healthy volunteers. The main pharmacokinetics parameters after oral administration of 100 mg mizoribine test or reference formulation were as follows: Cmax (1.00 +/- 0.21), (1.00 +/- 0.22) microg mL(-1); AUC(0-infinity) (6.72 +/- 1.39), (6.48 +/- 1.44) microg h mL(-1); t1/2 (2.77 +/- 0.26), (2.66 +/- 0.29) h; tmax (2.95 +/- 0.78), (2.84 +/- 0.50) h.

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.

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.

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 fourth generation poly( amidoamine) dendrimers ( G4. 0 PAMAM) functionalized multiwalled carbon nanotube ( G4 . 0-MWCNTs ) was prepared by amidation between carboxylated multiwalled carbon nanotube (MWCNTs) and G4. 0 PAMAM. Then a novel hydrogen peroxide (H2O2) sensor was fabricated by electrodepositing Pd nanoparticles (NPs) on a glassy carbon electrode (GCE) modified with G4. 0-MWCNTs composites. The modified electrode was characterized by field emission scanning electron microscopy ( FESEM) , cyclic voltammetry ( CV) and electrochemical impedance spectroscopy ( EIS) . A large amounts of highly dispersion PdNPs could be well loaded on the surface of the G4. 0-MWCNTs, and the modified electrode exhibited excellent electrocatalytic activity towards the reduction of H2 O2 . Under the optimized conditions, the reduction peak currents of H2 O2 were linear to their concentrations in the range from 1. 0 × 10-9 mol/L to 1. 0×10-3 mol/L and the limit of detection of 2. 3×10-8 mol/L was obtained. The recovery of standard addition for human serum samples was 96 . 7%-103 . 1%.