Objective To investigate the effect of glutaminase 1(GLS1)specific inhibitor BPTES[bis-2-（5-phenylacetamido-1,3,4-thiadiazol-2-yl）ethyl sulfide]on the liver fibrosis in the mouse model of liver fibrosis induced by carbon tetrachloride(CCl4).Methods Male C57BL/6J mice were intraperitoneally injected with olive oil(control group),10%CCl4(10 μL/g,model group)or 10% CCl4(10 μL/g)+ BPTES(10 mg/kg,treatment group),with 10 mice in each group,two doses a week for four weeks to establish liver fibrosis model. Collagen deposition in mouse liver tissue was observed by Sirius red staining. The expression levels of actin alpha 2(Acta2),collagen typeⅠalpha 1(Col1a1)GLS1 and GLS1 protein were detected by qRT-PCR and immunohistochemical staining.Results Compared with the control group,the liver tissue of mice in the model group was generally enlarged,the surface was not smooth and granular,and the ratio of liver mass to tibia length significantly increased(t = 2. 979,P < 0. 05);The Sirius red positive area of collagen deposition increased signifi-cantly in the liver tissue of mice in the model group(t = 7. 661,P < 0. 01),the relative expression levels of Acta2 and Col1a1 significantly increased(t = 4. 335 and 5. 319,respectively,each P < 0. 01),and the mRNA and protein levels of GLS1 significantly increased(t = 5. 319 and 9. 725,respectively,each P < 0. 01). However,compared with the model group,the BPTES treatment group had a reduction in liver mass,a significant reduction in the Sirius red positive area of collagen deposition in liver tissue(t = 7. 427,P < 0. 01),and a significant reduction in the relative expressions of Atca2 and Col1a1(t = 3. 713 and 2. 628,respectively,each P < 0. 05).Conclusion Inhibition of GLS1activity can significantly improve the degree of liver fibrosis induced by CCl4,providing a new idea for the treatment of liver fibrosis.

Granulocyte-Macrophage Colony-Stimulating Factor ; therapeutic use ; Humans ; Recombinant Fusion Proteins ; therapeutic use

Antiphospholipid Syndrome ; diagnosis ; etiology ; therapy ; Child ; Humans ; Lupus Erythematosus, Systemic ; complications ; Male

This paper studied the relationship between apolipoprotein E isoforms and hyperlipidemia among 92 cases of diabetes mellitus, 174 cases with impaired glucose tolerance and 124 sex-age-matched controls. The results demonstrated that the patients with abnormal glucose tolerance had higher frequency of E2/3 isoforms and lower frequency of E, / , in com parison with controls. Hyperlipoproteinemia were mainly related to hyperglycemia but the Apo E isoforms which ex pressed different alleles also associated with hyperlipoproteinemia.

Objective To explore the effect of progesterone on the rate of neuronal apoptosis and nitric oxide(NO) level in the cortex and hippocampus tissue of newborn rats with hypoxic-ischemic encephalopathy(HIE).Methods Thirty 7-day-old neonatal rats were randomly divided into 3 groups:sham-operated group,hypoxic-ischemic(HI) group and pretreatment group.Rats in HI group and pretreatment group were subjected to left common carotid artery ligation,then were exposed to 80 mL/L oxygen and 920 mL/L nitrogen gas in 37 ℃ closed container for up to 2.5 h to establish HIE model.Progesterone was injected intraperitoneally into rats in the pretreatment group respectively for 30 minutes before hypoxia,and solution was injected into the sham-operated group and HI group.All rats were killed at 24 h after operation.The neuron apoptosis was identified and analyzed by flow cytometry.Nitrate/nitrite was assayed to represent nitric oxide content of brain tissues.Results The ratio of neuronal apoptosis and NO contents in cortex and hippocampus tissue in HI group [(10.09?0.36)%,(12.32?0.28)%,(51.36?9.71) ?mol/L,(52.34?4.26) ?mol/L] were significantly higher than those in sham-operated group [(2.49?0.23)%,(2.58?0.26)%,(18.16?6.24) ?mol/L,(19.28?3.58) ?mol/L)](P_a

Animals ; Bronchopulmonary Dysplasia ; etiology ; Fibroblasts ; physiology ; Humans ; Hyperoxia ; pathology ; Infant, Newborn ; Lung ; embryology ; pathology

China ; Hospital Design and Construction ; standards ; Hospitals ; Humans ; Occupational Exposure ; analysis ; prevention & control ; Radiology Department, Hospital ; Safety ; standards

Objective To study the relationship between the gene mutations of DNA gyrase subunit A(gyrA)and quinolone resistance in Salmonella typhi. Methods The genes of gyrA DNA of Salmonella typhi S275(a clinically isolated quinolone susceptible strain)and its spontaneous quinolone-re-sistant mutant RGl were examined in this study with polymerase chain reaction(PCR),restrictive frag-ments length polymorphism(RFLP),single strand conformational polymorphism(SSCP)and nucleotide sequencing. Results Nudeotide sequencing of gyrA in Salmonella typhi S275 revealed that the bases of 128～426 kept highly conservative as compared with those of Escherichia coli KL-16,with only 7.49%difference in the gyrA nucleotides 128～426 between the two strains.Most of the mutations were silent mutations,which contributed to 3 amino acid substitutions in gyrase(including Thr-45→His,Arg-49→Leu and Val-56→Gly),and all these substitutions were located outside the quinolone resistance determining re-gion(amino acids 67-106 of subunit A of gyrase).In comparison with Salmonella typhi S275,a single mutation was found at base 247 of gyrA of Salmonella typhi RG1,with change transferred from T to G and led to a substitution of Ser-83→Ala.The mutation might be responsible for the increase of MICs of nalidixic acid,ofloxacin and ciprofloxacin against Salmonella typhi from 2,0.06 and<0.03 to 512,2,and 1 mg/L respectively.Ser-83→A1a was also a newly discovered substitution in gyrA of Salmonella spp.The results of PCR-RFLP and SSCP were in concordance with results of nucleotide sequencing. Conclu.sions The mutation of gyrase at the 83rd amino acid maybe play a principal role in the resistance of Salmonella typhi to quinolone.

BACKGROUND: Peroxisome proliferator-activated receptor-gamma(PPAR-γ) can restrain the inflammatory reaction of hypertrophic myocardium through restraining the expression of interleukin-6, cyclooxygenase, endothelin-1, nitricoxide synthase, matrix metalIoproteinase-9, gelatinase and adhesion molecule, etc.OBJECTIVE: To observe the influence of rosiglitazone sodium(the ligand for PPAR-γ) on inflammatory factors in rats with myocardial hypertrophy in the course of myocardial hypertrophy resulting from pressure load.DESIGN: Randomized controlled trial based on animals.SETTING: Department of Cardiovascular Surgery, Xinqiao Affiliated Hospital, the Third Military Medical University of Chinese PLA.MATERIALS: Fifty purebred male SD rats of S.P.F. Grade, whose body mass was (220±22) g.METHODS: The experiment was completed in the Institute of Battle Surgical Research, the Third Military Medical University of Chinese PLA from August 2004 to October 2005. Fifty rats were randomly divided into 5groups: control group, sham operation-normal saline group, sham operationrosiglitazone group, myocardial hypertrophy-normal saline group and myocardial hypertrophy-rosiglitazone group, 10 rats per group. The rat model of myocardial hypertrophy induced by pressure overload was established with the method of coarctation of abdominal aorta. Rosiglitazone group: At the postoperative 4th week, the rats were injected intraperitoneally with the Normal saline group: At the postoperative 4th week, the rats were injected intraperitoneally with normal saline[1 mL/(kg.d)] for 1 week. At the postoperative 5th week, the indexes of myocardial hypertrophy and hemodynamics were determined. The contents of tumor necrosis factor-α, platelet activating factor and myeloperoxidase in the left ventricle muscle were determined with radioimmunosorbent technique. The expression of PPAR-γ mRNA was detected with RT-polymerase chain reaction. The activity of nuclear factor-κB was detected with EMSA.MAIN OUTCOME MEASURES: The indexes of hemodynamics, cardiac ventricle reconstitution and cardiac muscle in the rat models.RESULTS: Except 1 rat in the control group died of the external injury induced by biting after 3 weeks, 49 of 50 rats entered the result analysis.①After the coarctation of aorta, the contents of tumor necrosis factor-α, platelet activating factor and myeloperoxidase of hypertrophic myocardium in the myocardial hypertrophy-rosiglitazone group were lower significantly than those in the myocardial hypertrophy-normal saline group(P ＜ 0.01-0.05), but they were still higher than those in the control group(P＜0.01).②The expressions of PPAR-γ mRNA of myocardial tissue in both the myocardial hypertrophy-rosiglitazone and myocardial hypertrophy-normal saline groups were higher obviously than those in the control group(P＜0.01), and those in the myocardial hypertrophy-rosiglitazone group were higher than those in the myocardial hypertrophy-normal saline group(P＜0.01).③The activity of nuclear factor-κB combined with DNA in cardiac muscle cell in both the myocardial hypertrophy-normal saline and myocardial hypertrophy-rosiglitazone groups were higher obviously than those in the control group (P＜0.01), and those in the myocardial hypertrophy-rosiglitazone group were lower obviously than those in the myocardial hypertrophy-normal saline group(P＜0.01).CONCLUSION: The increasing of pressure load induces myocardial hy pertrophy. The activation of nuclear factor-κB in the tissue of hypertrophic myocardium is strengthened obviously. The expressions of tumor necrosis factor-α, platelet activating factor and myeloperoxidase in hypertrophic myocardium increase. This inflammatory reaction, which is strengthened obviously, can be restrained by rosiglitazone sodium that is the synthetical lig and for PPAR-γ.

Objective To explore the influence of fluid management and prognosis guided by goal direction on patients undergoing gastrointestinal surgery.Methods Eighty ASA grade Ⅰ-Ⅲ,consecutive consenting patients undergoing gastrointestinal surgery were divided into observation group (40 patients)and control group (40 patients) by random digits table method.The intraoperative fluid management in control group was based on central venous pressure(CVP),and kept CVP at 8-10 mmHg(1 mmHg =0.133 kPa).The intraoperative fluid management in observation group was based on stroke volume variation (SVV),and kept SVV at 10 ％-12％.The operation time,intraoperative and postoperative 3 d fluid management,time of defecation and exhaust,time of full or semi-liquid diet,length of stay in hospital,rate of complications after operation for 48 h between two groups were compared.Results The volume of total fluid,colloid solution and crystalloid solution received during operation in observation group were significantly lower than those in control group[(2 686.0 ± 977.5) ml vs.(4 837.5 ± 1 566.0) ml,(792.4 ± 197.6) ml vs.(1 284.6 ± 356.7)ml,(1 894.9 ± 460.4) ml vs.(3 569.9 ± 1 318.7) ml] (P ＜ 0.05).The time of semi-liquid diet,length of stay in hospital in observation group were significantly lower than those in control group [(171.1 ± 45.3) h vs.(235.8 ±89.5) h,(11.4 ±1.8) d vs.(14.7 ±4.9) d] (P＜0.05).The time of full liquid diet,time of defecation and exhaust between two groups had no significant difference(P ＞ 0.05).The rate of complications between two groups had no significant difference(P ＞ 0.05).Conclusion Compared with monitoring CVP,the fluid management based on SVV can decrease the fluid volume during operation and shorten the length of stay in hospital.