Objective To investigate the effect of exogenous GAs on learning and memory capability of hypoxic-ischemic(HI) brain damage rats. Methods After ligation of the right carotid artery of 7-day old male SD rats and waiting for 4 hours of recovery, the rats were exposed to 8% oxygen-92% nitrogen gas mixture for 2 hours. The HI animals were randomly divided into 3 groups. GAs-treated group 1: animals were injected i.p. GAs immediately after HI every 12 hours for 4 doses with 50 mg/kg, followed by a 2 weeks consecutive daily injections at dose of 30 mg/kg/day. GAs treated group 2: rats received GAs 50 mg/kg immediately after HI every 12 hours for 4 doses, followed by injection of saline in the same volums for 2 weeks. Control group: rats received saline in the equivalent volums and duration. The behavioral test starded when the animals were 24 days old. Discriminative learning ability and memory retention were tested in the tri-equal-arms maze . The locomotor activity and alternative behavior was observed. The degree of neuronal damage were assessed after behavioral test. Results (1)The number of trails to reach the learning criteria were (39?17), (32?14)and (20?13) for control group, GAs-treated group 2 and GAs-treated group 1, respectively. The percentages of memory retention for control group, GAs-treated group 2 and GAs-treated group 1 were (62?10)%, (64?11)% and (70?9)%, respectively. Two weeks consecutive daily injection of GAs had facilitatory effects on learning ability and memory retention of HI rats(P0.05). Conclusion Gangliosides can enhance the learning ability and memory retention in neonate rats with HI.

NAT2 is an important drug metabolizing enzymes in humans.Polymorphisms in NAT2 gene produce variants at amino acid including seven mutation sites.In vivo NAT2 takes part in 20 kinds of drugs metabolism and activation of carcinogen.Polymorphism of NAT2 has been related to some diseases.This paper reviews the polymorphisms and genotyping about NAT2 and their implications in drug and clinical research.

Objective To explore the clinical features and gene mutations of blepharophimosis-ptosis-intellectual-disability syndrome (BPID). Methods The clinical data, diagnosis and treatment of a child with BPID in neonatal intensive care unit (NICU) were reviewed. Based on the literature retrieved from PubMed database, the common classification, clinical features, diagnosis and genetic counseling of BPID and its affiliated blepharophimosis-mental retardation syndromes (BMR) were reviewed. Results This male infant was 39 weeks of gestational age with birth weight of 1920 g, and was admitted to NICU 15 min after birth due to dyspnea. The main clinical manifestations were facial deformity such as biepharophimosis, ptosis and micromandible, inspiratory dyspnea with laryngeal cartilage softening, malformations of the thorax and feeding difficulties. A heterozygous mutation in UBE3B gene was identified by complete exon sequencing and he was diagnosed of BPID, a rare genetic disorder. Reviewing the literature, there was no relevant report in domestic. While one foreign literature was found to report 5 patients from 4 families having a subtype of BMR, a kind of autosomal recessive diseases caused by mutations in the UBE3B gene. Conclusion BPID is a rare clinical entity of BMR. Complete exon sequencing can be used to diagnose the disease.

AIM　To develop a sensitive, specific and reliable reversed-phase high performance liquid chromatographic method(RP-HPLC) to determine the total and unbound(free) concentrations in human plasma of amitriptyline and its major metabolite, nortriptyline. METHODS The assay involved a simple extraction procedure. The mobile phase consisted of acetonitrile and distilled water(30∶70, V/V), containing triethylamine(0.5%) and orthophosphoric acid(0.3%), pH 3.1. Separation was achieved on the C18 ODS column and the effluent was measured for UV absorption at 240 nm. RESULTS　The calibration curves were linear in the range of 4～400 μg*L-1 for total concentration, and in the range of 4～64 μg*L-1 for free concentration for both amitriptyline and nortriptyline. The lowest limits of detection were 4 μg*L-1 for both compounds. The absolute recovery rates were 102.0%±3.77% for amitriptyline and 99.3%±7.13% for nortriptyline. The precision values(RSD) of intra-day and inter-day for both amitriptyline and for nortriptyline were determined to be <5%, and <8%, respectively. The method was applied to determine the total and free concentrations in plasma of the healthy volunteers after a single oral dose of 50 mg amitriptyline. CONCLUSION　The assay was simple, repid, highly selective and sensitive. It is suitable for the routine analysis of total and free drug concentrations in plasma using readily available instruments with lower cost.

Aim To investigate the effects of CYP2C19 polymorphism on the pharmacokinetics and comparative bioavailability of omeprazole in Chinese population.Methods Eighteen healthy male volunteers were selected,of whom 6 were CYP2C19 wild type(w/w),6 were CYP2C19 heterozygous variant(w/m) and the rest were CYP2C19 homozygous variant(m/m).A randomized two-period crossover study was performed.Subjects were assigned to receive test or reference omeprazole as a single oral dose of 40 mg randomly.After a washout period of one week,subjects received the alternative omeprazole formulation.Multiple blood samples of 3 ml were obtained over 12 h after dosing and plasma concentrations of omeprazole were measured by LC/MS method.The modeling of individual pharmacokinetics and the pharmacokinetic parameters of omeprazole were estimated by 3P97.Results The AUC and Cmax of reference omeprazole formulation in w/w,w/m,m/m groups were 1178.44±340.24,2328.10±1011.83,5062.02±1097.29 μg·h·L~(-1) and 602.87±118.25,926.43±134.48,1406.29±233.58 μg·L~(-1),respectively,with significant differences among the three groups(P<0.05).Significant differences were also observed in other pharmacokinetic parameters such as k_e、CL/F、t_(1/2) and Vd/F among the three groups(P<0.05).With regard to test omeprazole formulation,the AUC and C_(max) in w/w,w/m,m/m groups were 1224.82±531.67,2723.34±519.29,5692.49±1575.35 μg·h·L~(-1) and 618.74±231.43,910.67±125.99,1303.31±152.01 μg·L~(-1),respectively,which,as well as k_e,CL/F,t_(1/2) and Vd/F were significant different among the three groups(P<0.05).No significant differences were observed in comparative bioavailability among groups with the values of 94.29%±14.06%,93.08%±11.22%,91.84%±13.03% in w/w,w/m,m/m groups respectively(P>0.05).Conclusions Different CYP2C19 genotypes,leading to functional heterogeneity of CYP2C19,may affect pharmacokinetic profile of omeprazole.Therefore,genotyping CYP2C19 gene before omeprazole therapy will be of great benefit for optimizing individual therapy regimen.There is no significant difference of omeprazole comparative bioavailability with regard to CYP2C19 genetic polymorphism.

BACKGROUND: The mitofusin 2 (Mfn2) may affects vascular smooth muscle cell Ras protein and suppress cellular proliferation through inhibition of extracellular signal-regulated protein kinase signaling pathway, which plays an important role in pathogenesis of vascular disorders such as hypertension, atherosclerosis and post-angioplasty restenosis. Mfn-2 gene amino acid sequence of the first 442 serine serves as protein kinase A (PKA) phosphorylation site, which is closely related to its phosphorylation status and may be involved in its functional regulation.OBJECTIVE: To investigate the effect of Mfn2 gene with PKA phosphorylation site deletion[Mfn2-PKA (△)] on inhibiting the proliferation of vascular smooth muscle cells and related signaling pathway.METHODS: Vascular smooth muscle cells of rats infected by recombinational adenovirus carrying green fluorescent protein,Mfn2 gane and Mfn2-PKA (△), were subcultured for 3-10 passages and randomly divided into 4 groups: ① Control group without intervention. ② Control group infected with adenovirus carrying green fluorescent protein. ③ Experiment group infected with adenovirus carrying Mfn-2 gene.④ Experiment group infected with adenovirus carrying Mfn2-PKA (△). Laser confocal microscopy was used to observe the locations of Mfn2 gene with and without PKA in cells. The expressions of extracallular signal-regulated protein kinase, Mfn2 gone and Mfn2-PKA (△) were determined by Western blot analysis. The growth curve of the vascular smooth muscle cells was explored by MTT.RESULTS AND CONCLUSION: The Mfn-2 and Mfn2-PKA (△) both expressed protein-specific bands in vascular smooth muscle cells. Two kinds of gone expression products were mainly located at the out membrane of mitochondria. Compared with the control group and adenovirus carrying green fluorescent protein group, the absorbance values at 3, 4, 5, 6 days were significantly reduced in adenovirus carrying Mfn2 group (P ＜ 0.01), and no obvious changes were observed in adenovirus carrying Mfn2-PKA (△) group. Compared with the control group and adenovirus carrying green fluorescent protein group, the extracellular signal-regulated protein kinase expression was significantly reduced in adenovirus carrying Mfn2 group (P ＜ 0.01), and no obvious changes were observed in adenovirus carrying Mfn2-PKA (△) group. Mfn2-PKA (△) located at the out membrane of mitochondria, has no effect on suppressing the proliferation of vascular smooth muscle cells, and no inhibition effect on extracellular signal-regulated protein kinase signaling pathway.

Objective To explore the effect of domoxifen combined with tamoxifen on ovulation in clomiphene-resistant patients with polycystic ovary syndrome. Methods 100 patients who was resistant to CG were randomly divided into two groups:the treatment group (group A) and control group (group B). Oral dosing CC 100mg/d to the patients of group A in the first 3th to 7th days of menses,at the same time,oral dosing tamoxifen 40mg/d in the first 3th to 7th days of menstrual cycle. The dose of CC to group B was same as group A. Beginning to monitor the case of follicular growth during the 8th day of menses. When a ovarian follicle' s diameter beyond 18mm or 2 ovarian follicle' s diameter beyond 17mm, intramuscular injection hCG 10 000IU, sexing after 36 hours later. Observing the two groups of the mature ovarian number,the endometrial thickness, the days of promoting ovulation ,the level of progesterone in serum about the 22th day of menstrual cycle, ovulation rate and pregnancy rate, after injecting hCG.Results The day after injecting hCG, the mature ovarian follicle number,the endometrial thickness, the level of progesterone in serum about the 22th day of menstrual cycle,ovulation rate and pregnancy rate,group A was significantly different from group B( P ＜0.05 ～ P ＜0. 01 ) ,the days of promoting ovulation have no statistically significant differences between the groups (P ＞ 0. 05). Conclusion In the clomiphene-resistant patients with polycystic ovary syndrome,tamoxifen could promote ovulation,improve the effect of CC on the uterus' s anti-estrogen,increase endometrial thickness, elevate ovulation rate and pregnancy rate.

Purpose To investigate the feasibility of 30 ml low-dose contrast medium in reducing the accumulation of contrast medium in venous system while maintaining enough artery enhancement in 256-slice CT angiography (CTA) of intracranial and cervical arteries.Materials and Methods Sixty patients with head and neck CTA were recruited prospectively,and they were randomly divided into group A and group B.The scan parameters of the two groups were identical,but the protocol of contrast medium injection was different.Group A was injected 60 ml contrast medium and 30 ml saline successively with the rate of 4.0 ml/s.Group B was injected 30 ml contrast medium and 50 ml saline successively with the rate of 5.0 ml/s.CT attenuation values of aortic arch,common carotid artery,subclavian artery,cerebral middle artery,superior vena cava,innominate vein,subclavian vein,internal jugular vein were measured,and the image quality was evaluated.Results The average CT values of superior vena cava,right innominate vein,right subclavian vein in two groups had significant differences (P＜0.05).The average CT values of left brachial vein,left subclavian vein,left and right internal jugular vein in two groups had no significant differences (P＞0.05).The average CT values of aortic arch,left and right common carotid artery,left and right subclavian artery,left and right cerebral middle artery in two groups had significant differences (P＜0.05).The scores of image quality in two groups also had significant difference (P＜0.05).Conclusion Head-and-neck CTA with 30 ml low-dose contrast medium is feasible and the images are satisfactory for diagnosis,which can reduce the dose of contrast medium and accumulation of contrast medium in venous system,while maintaining enough artery enhancement.

Objective:To clarify the relationship between epidermal growth factor receptor (EGFR) mutations and the clinicopathologic features of primary lung adenocarcinomas in Xinjiang.Methods:The mutations of EGFR gene at exons 18 -21 in 59 cases (including 15 cases of Uighur and 44 cases of Han) of lung adenocarcinoma tissues,which were obtained from surgical resection,were detected by amplifica-tion refractory mutation system (ARMS)method.And the relationships among mutations,race and clini-copathologic features were analyzed.Results:The frequencies of EGFR mutations in lung adenocarcinoma were 20% for Uighur,which was lower than that in Han (54.5%),P <0.05.The deletion mutations at exon 19 were seen in 2 of 15 Uighur cases and 9 of 44 Han cases.EGFR mutations were present,inclu-ding exon 21 L858R in one Uighur case and 12 Han cases,exon 18 G719X in two of 44 cases of Han, exon 21 L861Q in one of them.On histological type,the frequencies of EGFR mutation in alveolar pre-dominant adenocarcinoma was 71% (22 /31),which was higher than both that in solid predominant and mucinous carcinoma (6.7%,20% respectively).According to statistic analysis,EGFR mutations were without correlation with the patient’s gender,age,location,gross type,smoking status and lymph node metastasis(P >0.05).EGFR mutation was more frequent in well-differentiated cancer,mainly in acinar carcinoma,while poorly differentiated adenocarcinoma and mucous adenocarcinoma were lower.Conclu-sion:There was a difference of EGFR mutation in primary lung adenocarcinoma between Uighur and Han in Xinjiang,perhaps reflecting ethnic genetic variation,which is worth further analyzing.EGFR mutation was commonly detected in well or middle differentiated adenocarcinoma,mainly in acinar carcinoma.

AIM:To study the pharmacokinetics and relative bioavailability of citalopra hydrobromide in human plasma.METHODS:The citalopra hydrobromide concentrations in plasma were determined by HPLC-UV.The column was Lichrospher ODS(5 ?m,250 mm?4.6 mm).The mobile phase was acetonitrile-0.1 mol/L KH2PO4 buffer-triethylamine(35:65:0.3,v/v/v).The flow rate was 1 mL/min.The detection wavelength was 240 nm.The test and reference formulations of citalopra were given to 18 healthy male volunteers.RESULTS:The calibration curve was linear within the range of 2-128 ?g/L,r=0.9992.The minimum detection limit was 1 ?g/L.The recovery was 80%-88%,the RSDs of inter-day and intra-day were not more than 15%.After a single oral dose of 20 mg citalopra hydrobromide was given,the main pharmacokinetic parameters tmax were(4.6?1.0),(4.4?1.4) and(4.0?1.4) h;Cmax were(70?19),(71?17) and(66?21) ?g/L;and t1/2 were(37?9),(37?6) and(36?6) h respectively.CONCLUSION:No significant difference exists among the pharmacokinetic parameters of the three formulations.They are bioequivalent.