Cardiovascular System ; Pharmacogenetics

Objective To investigate the effect of propofol anesthesia on the expression of β-secretase 1 (BACE1) and content of anyloid beta protein 1-42 (Aβ1-42) in the neonatal rat hippocampus.Methods Ninety Sprague-Dawley rats,aged 7 days,weighing 12-16 g,were randomly divided into 3 groups ( n =30 each):control group (group C),single dose of propofol anesthesia group (group SP),and repeated doses of propofol anesthesia group (group RP).Group C received intraperitoneal normal saline 7.5 ml/kg once a day for 7 consecutive days.Group SP received normal saline 7.5 ml/kg once a day for 6 consecutive days and propofol 75 mg/kg on 7th day.Group RP received propofol 75 mg/kg once a day for 7 consecutive days.Six rats in each group were chosen at 15 min after the end of injection on 7th day and blood samples were taken from the left ventricle for determination of the blood glucose level and for blood gas analysis.Eight animals in each group were sacrificed on 1st,3rd and 7th day after the end of injection on 7th day to determine the expression of BACE1 (using Western blot) and content of Aβ1-42 in the hippocampus (by ELISA).Results Compared with groups C and SP,the expression of BACE1 was up-regulated and the content of Aβ1-42 was significantly increased at each time point in group RP ( P ＜ 0.01 ).There was no significant difference in the expression of BACE1 and content of Aβ1-42 at each time point between groups C and SP ( P ＞ 0.05).Conclusion Repeated doses of propofol up-regulate the expression of BACE1 and increase the content of Aβ1-42 in neonatal rat hippocampus,which may be one of the mechanisms by which propofol leads to long-term cognitive dysfunction.Single dose of propofol does not have the effect.

Objective To evaluate the role of prostaglandin E2 (EP) receptors in H9c2 cardiomyocyte hypertrophy induced by prostaglandin E2 (PGE2).Methods Primary cultured H9c2 cardiomyocytes were seeded in culture flasks (3 ml/flask) or in 24-well plate (1 ml/hole) or 6-well plate (2 ml/hole) with density of 4 × 104/ml.The cells were randomly divided into 4 groups (n=24 each): control group (group C),PGE2 group,AH6809 (EP1 and EP2 receptor antagonist) group (group A) and GW627368X (EP4 receptor antagonist) group (group G).The cells were continuously cultured for 48 h.PGE2 (final concentration 1 μmol/L) was added to the culture medium in PGE2 group.PGE2 (final concentration 1 μmol/L) and A H6809 (final concentration 10 μmol/L) were added to the culture medium in group A.PGE2 (final concentration 1 μmol/L) and GW627368X (final concentration 10 μmol/L) were added to the culture medium.The cells were then cultured for 48 h in groups PGE2,A and G.Then the cell morphology was observed by using fluorescent microscope.The cell diameter was measured by using the Image J medical image analysis system.Total protein content in the cells was measured with BCA method.The expression of atrial natriuretic peptide (ANP) mRNA and brain natriuretic peptide (BNP) mRNA in the cytoplasm was determined using RT-PCR.Results Compared with group C,the total protein in the cells and cell diameter were significantly increased,and the expression of ANP mRNA and BNP mRNA in the cytoplasm was up-regulated in groups PGE2,A and G (P ＜ 0.05).Compared with group PGE2,the total protein in the cells and cell diameter were significantly decreased,and the expression of ANP mRNA and BNP mRNA in the cytoplasm was downregulated in group G (P ＜ 0.05),and no significant change was found in the parameters mentioned above in group A (P ＞ 0.05).Conclusion EP4 receptor mediates H9c2 cardiomyocyte hypertrophy induced by PGE2 and the effect is not related to EP1 and EP2.

Objective To study the effects of using the dropping retention-enema in the clinical practices.Methods Divided 60 cases who need retention-enema into the experimental group and the control group,there were 30 cases in the each group.The traditional retention-enema method was used in the control group,while the dropping retention-enema method was used in the experimental group.Compared the related factors between the two groups.Results All the factors which can indicated the clinical effects in the experimental group were better than those of in the control group,P

The formative assessment system has been applied to the internship education for the clinical anesthesia with the aim to improve students' initiative and to evaluate their outcomes more compre-hensively. The students' performance in the shift exchange, case discussion, raising question, solving question at the time points of after the preclinical train, one month and 3 months into the anesthesia internship, and after the completion of internship, and their capability in preoperative patient assessment, condition report, clinical practice, review writing have been evaluated to determine the educational quality and to instruct the improvement of educational approach. Assess process takes into account both the individuality and the gen-eral character of the students and feedbacks the evaluation result to improve the practice teaching The im-plementation of the evaluation can promote students' autonomous learning and comprehensively evaluate students' practice process.

Humans ; Enhanced Recovery After Surgery ; Stomach Neoplasms/surgery* ; Length of Stay ; Laparoscopy ; Postoperative Complications ; Gastrectomy

Objective To study the action of apolipoprotein E genetic polymorphism on the efficacy of Tanshinol.Methods Through detecting the expression of low density lipoprotein receptor mRNA and 3-hydroxy-3 -methylglutaryl coenzyme A reductase mRNA in L -02 cells by reverse transcription-polymerase chain reaction , to compare the effect of different genetic subtypes of ApoE on Tanshinol.Results Apolipopro-tein E can weaken the induction of low density lipoprotein receptor ex-pression caused by Tanshinol.The weakening extent of apolipoprotein E 2 (Arg112Cys)was stronger than apolipoprotein E3 and apolipoprotein E4 ( Cys 158 Arg) ( P<0.01 ).Apolipoprotein E also can enhance the inhi-bition of 3-hydroxy -3-methylglutaryl coenzyme A reductase expres-sion, especially apolipoprotein E4 (P<0.01).But apolipoprotein E2 or apolipoprotein E3 can not have statistical significance ( P >0.05 ).Conclusion Both 112 and 158 site might be the key site that have effect on the efficacy of Tanshinol.

This study examined the expression pattern of programmed cell death 5 (PDCD5) in cochlear hair cells and spiral ganglion neurons (SGNs) and its association with age-related hearing loss in mice. Sixty C57BL/6J (C57) mice at different ages were divided into four groups (3, 6, 9 or 12 months). PDCD5 expression was detected by using immunohistochemistry, real-time PCR and Western blot. Morphological change of the cochleae was also evaluated by using immunoassay. The results showed that the expression of PDCD5 had a gradual increase with ageing in both protein and RNA levels in C57 mice, as well as gradually increased apoptosis of cochlear hair cells and SGNs. In addition, we also found that caspase-3 activity was enhanced and its expression was enhanced with ageing. It is implied that overexpression of PDCD5 causes the increase in caspase-3 activity and the subsequent increase of apoptosis in cochlear hair cells and SGNs, and thereby plays a role in the pathogenesis of presbycusis. Thus, PDCD5 may be a new target site for the treatment and prevention of age-related hearing loss.

MicroRNA is a class of small noncoding single-stranded molecule RNA,which regulates the expression of target genes through binding with the 3'-untranslated region of target gene mRNA.In recent years,researches about microRNA regulating transporter have attracted widespread attention.With more in-depth researches,it was found that not only can microRNA directly target the mRNA of transporters,but also it can regulate some signal proteins of classic pathway to control the expression of transporters indirectly.This review summarizes the research progress of microRNAs on the regulations of several important transporters.

Objective To study the mechanism of organic anion trans-porting polypeptide1B1 (OATP1B1) and cytochrome P2C9 (CYP2C9 ) genetic polymorphism effect on the metabolism and transport of fluvasta-tin.Methods Build OATP1B1*1a,*5and*15 recombinant plasmid model and CYP2C9*1,*3 recombinant enzyme model to compare up-take and enzymatic kinetic parameters of fluvastatin in different models.Results The fluvastatin intake of OATP1B1*5 gene, OATP1B1*15 gene, OATP1B1*1a gene are ( 3.27 ±0.53 ), ( 6.88 ±2.01 ), (6.32 ±1.23 ) pmol· min-1· mg-1 protein.Compared with OATP1B1*1a, OATP1 B1*5 reduces the transport capacity of fluvastatin ( P <0.05 ) and OATP1B1*15 gene increases (P<0.05).The CLintof CYP2C9*3 and CYP2 C9*1 metabolizing fluvastatin are 0.42 , 1.25 ( P<0.05 ).The activities of CYP2C9*3 are lower than CYP2C9*1.Conclusion The OATP1B1 521 site and the CYP2C9 359 site might be the molecular action site of transport fluvastatin.Therefore , more attention should be payed in clinical applications to prevent damage caused by OATP 1B1 and CYP3A4 genetic polymorphism.