BACKGROUND: As a kind of polypeptide, angiotensin-converting enzyme (ACE) inhibitory peptide can lower the blood pressure of human body through restraining the formation of angiotensin Ⅱ.OBJECTIVE: To investigate the influence of AGE inhibitory peptide on endothelial cell proliferation and endothelin expression in cultured human umbilical vein cells based on cellular and molecular levels in order to provide the experimental evidences for ACE inhibitory peptide to be the potential blood pressure-lowering health food.DESIGN: Repeated measures design.SETTING: School of Bioscience and Bioengineering, South China University of Technology; School of Applied Chemistry and Biological Technology,Shenzhen Polytechnic.MATERIALS: The experiment was carried out in the Institute of Applied Chemistry and Biological Technology, Shenzhen Polytechnic from September 2004 to March 2005. The AGE inhibitory peptide was provided by the Institute of Applied Chemistry and Biological Technology, Shenzhen Polytechnic. Under certain circumstance, 15 μ mol/L of the inhibitor was needed to decrease half of the AGE activity. The human umbilical vein endothelial cells of the 4th generation were cultured randomly in 7 groups with different concentrations: medium group, 150, 300 and 600 mg/L ACE inhibitory peptide groups, captopril group, norepinephrine(NE) group, and ACE inhibitory peptide+NE group.METHODS: ①The endothelial cells were cultured as recommended. The medium was M199+FBS(0.15, v/v)+penicillin(10 000 U/mL)+streptomycin (100 mg/L). After cellular fusion, the cells were carried on the passage with the ratio of 1:2. The 4th generation cells were used for experiment. ②M199(0.15, v/v) was contained in each group. ACE inhibitory peptides were added to make the final concentration 150, 300 and 600 mg/L in the 150, 300 and 600 mg/L ACE inhibitory peptide groups respectively. Captopril was added to make the final concentration 10-5 mol/L in the captopril group. NE was added to make the final concentration 100 μg/L in the NE group. ACE inhibitory peptide and NE were added to make the final concentration 300 mg/L and 100 μg/L in the ACE inhibitory peptide+NE group respectively. ③The state of cell growth was determined with cytometry. The contents of endothelial cells in the medium with different culture times were determined with radioimmunoassay. The expression of endothe lin mRNA was determined with reverse transcriptase-polymerase chain reaction. The expression of cellular endothelin protein was determined with immunohistochemical method.MAIN OUTCOME MEASURES: ①The influence of ACE inhibitory peptide on endothelial cell proliferation. ②The influence of ACE inhibitory peptide on the endothelin mRNA and endothelin protein.RESULTS: ①The influence of ACE inhibitory peptide on endothelial cell proliferation and endothelin secretion: Compared with the medium group,in the captopril and 150, 300, 600 mg/L ACE inhibitory peptide groups,the growth of endothelial cells was restrained and the endothelin content in the medium was lowered(P ＜ 0.01 or 0.05). NE could promote the growth of endothelial cells and the secretion of endothelin, but the cell density and endothelin content after treatment with ACE inhibitory peptide were similar to those in the medium group (P ＞ 0.05). ②The influence of ACE inhibitory peptide on the expressions of endothelin mRNA and protein in endothelial cells: Compared with the medium group, the expressions of endothelin mRNA and protein might be lowered in the captopril and 150,300, 600 mg/L ACE inhibitory peptide groups(P ＜ 0.01 or 0.05). The expressions of endothelin mRNA and protein could be up-regulated by NE.The gene expression after treatment with ACE inhibitory peptide was similar to that in the medium group(P ＞ 0.05).CONCLUSION: The ACE inhibitory peptides of different dosages can all restrain the growth of endothelial cells, lower the endothelin content, decrease the expression of endothelin gene and resist NE improved growth and secretion of endothelial cells in umbilical vein cell effectively.

Objective To optimize the preparative procedure for stachydrine in Fructus Leonuri. Methods The preparation was screened by orthogonal experiment, and a mathematical model of relationship of extraction time, methanol concentration, and solid-liquid ratio with the content of stachydrine hydrochloride was established by using back-propagation (BP) neural network. And the process parameters were optimized with genetic algorithm (GA) . Results The optimum process parameters were as follows: extraction with 69% of methanol concentration and with solid-liquid ratio being 11 times for 62 min. The content of stachydrine obtained by BP neural network modeling and GA was higher than that achieved by orthogonal experiment. Conclusion The optimum preparative procedure could be achieved by combining BP modeling with GA. The model developed in this study was proved to be predictable and feasible for the optimization of process parameters of multi-dimension nonlinear system.

Objective:To explore the relationship between respiratory mechanics and right heart function during ARDS mechanical ventilation through the establishment of Beagle dogs acute respiratory distress syndrome (ARDS) animal model and the application of different levels of mechanical ventilation, which will provide theoretical basis for right heart protective ventilation strategy of ARDS.Methods:Beagle dogs were anesthetized successfully and then pulmonary artery floating catheter, esophageal manometric catheter and femoral artery catheter were inserted. Under the pressure control mode, the driving pressure was fixed. After adjustment, PEEP gradually increased from 2 cmH 2O to 14 cmH 2O. The changes of respiratory mechanics, hemodynamics and right heart function were observed. ARDS model was established by injecting oleic acid into central vein, and mechanical ventilation with the same parameters was given after the model was established successfully. In contrast to itself, the changes of respiratory mechanics, hemodynamics and right heart function indexes of experimental dogs before and after modeling were analyzed. In the group, the indexes of different PEEP were compared by ANOVA, and then compared by Student-Newman-Keuls. The difference was statistically significant at a P value <0.05. Results:Before modeling, the peak airway pressure (P peak) and plateau pressure (P plat) increased with the increase of PEEP ( F=232.733,196.33, P<0.05). However, P trans-I, P trans-E, C stat and Vt decreased significantly ( F=4.524, 6.499, 64.803, 2.31, P<0.05). The area of change of right ventricle (FAC) became smaller ( F=3.09, P<0.05); SV first increased and then decreased ( F=3.24, P<0.05), and CVP and MPAP increased ( F=19.07,14.81, P<0.05). There was no significant difference in TAPSE, MAP, HR and SpO 2 ( P>0.05). After modeling, as PEEP increased, P peak, P plat, P ES-I and P ES-E increased significantly ( F=24.829, 41.95, 9.78, 87.86, P<0.05). Vt, P trans-I, P trans-E, C stat and Vt first increased and then decreased ( F=2.91, 4.29, 5.84, 48.890, P<0.05). TAPSE and SV first increased and then decreased ( F=6.22,6.54, P<0.05). CVP and MPAP increased ( F=5.23, 19.24, P<0.05). MAP increased first and then decreased ( F=5.02, P<0.05). SpO 2 increased ( F=2.77, P<0.05). FAC and HR had no statistical significance ( P>0.05). Conclusions:Trans pulmonary pressure and lung compliance can reflect the effectiveness of ARDS lung recruitment, and have good synergy; with the increase of PEEP, the right ventricular systolic function TAPSE is first affected, and SV compensatory increase, but with the increase of PEEP, TAPSE and SV decrease; pulmonary blood flow distribution is more important in improving alveolar oxygenation. Therefore, real-time monitoring of trans pulmonary pressure, TAPSE and intrapulmonary blood flow should be performed in ARDS treatment.

Objective To explore the value ofintraoperative CT (iCT) in endoscopic endonasal surgery for pituitary adenomas.Methods A retrospective analysis was conducted in the clinical data of 37 patients with pituitary adenomas performed endoscopic endonasal surgery with assistance of iCT in our hospital from November 2012 to June 2013.The influences of iCT on surgical process and results were analyzed.Results Intraoperative scanning was performed 1 to 3 times in each patient,averaging 1.43 times.The scanning time was only 50-60 s.Among the 37 patients,iCT revealed residual tumor in 11,9 of which underwent further resection with total removal in 6 and subtotal in 3,and the tumors in the other two patients were unable to be resected because the adenomas were tenacious and adhered closely to the internal carotid artery.Finally,the rate of gross total removal increased from 70.3％ to 86.5％,rising by 16.2％.No iCT related complications and severe surgical complication occurred.Conclusion The application of iCT in endoscopic endonasal surgery for pituitary adenomas provides objective evidence for the guidance of surgical procedure and real-time judgment of surgical results,which not only leads to higher percentage of tumor removal but also eliminates the unnecessary blind surgical manipulation to increase the safety of the operation.

Senescence of activated hepatic stellate cells (aHSCs) is a stable growth arrest that is implicated in liver fibrosis regression. Senescent cells often accompanied by a multi-faceted senescence-associated secretory phenotype (SASP). But little is known about how alanine-serine-cysteine transporter type-2 (ASCT2), a high affinity glutamine transporter, affects HSC senescence and SASP during liver fibrosis. Here, we identified ASCT2 is mainly elevated in aHSCs and positively correlated with liver fibrosis in human and mouse fibrotic livers. We first discovered ASCT2 inhibition induced HSCs to senescence in vitro and in vivo. The proinflammatory SASP were restricted by ASCT2 inhibition at senescence initiation to prevent paracrine migration. Mechanically, ASCT2 was a direct target of glutaminolysis-dependent proinflammatory SASP, interfering IL-1α/NF-κB feedback loop via interacting with precursor IL-1α at Lys82. From a translational perspective, atractylenolide III is identified as ASCT2 inhibitor through directly bound to Asn230 of ASCT2. The presence of -OH group in atractylenolide III is suggested to be favorable for the inhibition of ASCT2. Importantly, atractylenolide III could be utilized to treat liver fibrosis mice. Taken together, ASCT2 controlled HSC senescence while modifying the proinflammatory SASP. Targeting ASCT2 by atractylenolide III could be a therapeutic candidate for liver fibrosis.