1.Protective effect of heme oxygenase-1 and its reaction product,carbon monoxide on acute liver injury induced by carbon tetrachloride in rats
Tao WEN ; Jinyuan ZHAO ; Shuang MEI ; Li GUAN ; Yanlin ZHANG
Journal of Peking University(Health Sciences) 2003;0(06):-
Objective:To investigate the protective role of heme oxygenase-1 and its reaction product,carbon monoxide against acute liver injury induced by carbon tetrachloride in rats.Methods: Thirty male Sprague-Dawley rats were randomly divided into six groups with five in each.The control group received a single dose of corn oil injection.Carbon tetrachloride was injected intraperitoneally(i.p) to establish acute liver injury models in rats.Hemin(50 ?mol/kg) was administered i.p.12 hours before CCl_4 treatment,with an aim to induce HO-1 protein expression in the liver of rats.Carbon monoxide was injected i.p.12 hours prior to CCl_4 injection,resulting in about 8%-12% carboxyhemoglobin concentration in vivo.The expression of HO-1 in the liver of hemin-treated rats was determined by western blot method at different time points.At 24 h after carbon tetrachloride administration,all rats were sacrificed to collect blood samples for the examination of ALT,AST levels and to remove liver tissues for analysis of MDA concentration,SOD activity and caspase-3 activity as well as TNF-a contents.In addition,histopathological changes were investigated and hepatocyte apoptosis was detected by TUNEL method.Results: The administration of carbon tetrachloride to rats caused a marked hepatic damage,characterized by significant elevation of serum ALT,AST levels(2 136.3?163.4 U,1 422.7?221.7 U) and liver MDA con-tent(5.28?0.93 ?mol/g),caspase-3 activitiy(optical density value(4.69)?1.02) and TNF-? level(256.3?27.3 ng/L) combined with a remarkable reduction in liver SOD activity(45.9?14.8 U/mg) as compared with the control rats.Histopathological observations revealed severe damage in the liver and prominent hepatocyte apoptosis took place in CCl_4treated rats.However,pretreatment with hemin could induce high expression of HO-1 protein and exert potent protective effects against liver injury,as demonstrated by a significant decrease in ALT,AST levels(287.1?24.3 U,246.2?21.7 U) and MDA concentration(3.27?1.34 ?mol/g),reduction in caspase-3 activity(optical density value 2.49?1.47) and TNF-? level(132.6?19.5 ng/L),as compared with the CCl_4-treated rats.Moreover,hepatocyte apoptosis and liver injury were both attenuated remarkably in the liver of rats pretreated with hemin.In contrast to hemin administration,single injection of exogenous CO produced the same protective effects,as indicated by the remarkable reduction of ALT,AST levels and caspase-3 activity and TNF-a levels.Conclusion: The above results suggest that HO-1/CO system has a potent protective effect on acute liver injury induced by carbon tetrachloride in rats.Induction of HO-1 expression and low concentration of CO can inhibit the progress of hepatic damage,which might be due to the alleviation of lipid peroxidation and reduction of caspase-3 activity or inhibition of TNF-? level.
2.Study on the Improvement of Processing Method of Carapax Trionycis
Wen XIANG ; Min CHEN ; Jiadong ZHANG ; Lingling GUAN ; Zhaorong MIAO
China Pharmacy 2016;27(1):82-85
OBJECTIVE:To explore the optimal steaming time of Carapax trionycis during cleansing period,and to optimize and improve production technology of Carapax trionycis recorded by current Chinese Pharmacopoeia. METHODS:The mechanical processing replaced the artificial processing method in Chinese Pharmacopoeia. The content of protein and the appearance of Cara-pax trionycis were investigated after steaming for 30,60,90,120,180,240 min during cleansing period. The extract,decoction, ash content,appearance and property of Carapax trionycis decoction piece processed with vinegar were also investigated after cleansed Carapax trionycis decoction piece was processed by sand scalding and vinegar quenching method. RESULTS:The differ-ent steaming time obtained different quality of cleansed Carapax trionycis decoction piece and Carapax trionycis decoction piece pro-cessed with vinegar. Compared with decoction piece steamed for other duration,when the steaming time was 90 min,the content of protein in cleansed Carapax trionycis decoction piece was higher(31.16%),and its appearance was up to the requirement. Cara-pax trionycis decoction piece processed with vinegar had higher contents of extract and decoction(9.13%,11.39%)and lower con-tent of ash(66.29%),and its appearance was up to the requirement. CONCLUSIONS:Different steaming time have certain effect on the quality of cleansed Carapax trionycis and Carapax trionycis processed with vinegar,the optimal steaming time of Carapax tri-onycis is about 90 min during cleansing. The mechanical processing method maybe replace the artificial processing on Carapax tri-onycis for improving its production efficiency.
3.Effect of Actinidia chinensis planch polysaccharide on the growth and apoptosis, and p-p38 expression in human gastric cancer SGC-7901 cells.
Wen-Ying SONG ; Guan-Hua XU ; Guang-Ji ZHANG
Chinese Journal of Integrated Traditional and Western Medicine 2014;34(3):329-333
OBJECTIVETo investigate the effect of Actinidia chinensis Planch polysaccharide (ACPS) on the growth and apoptosis of human gastric cancer SGC-7901 cells, and to explore the effect of SGC-7901 cells on p-p38 expression.
METHODSThe inhibition rates at different concentrations of ACPS on SGC-7901 cells at 24, 48, and 72 h were detected using CCK-8 method. Apoptosis ratios in SGC-7901 were determined by flow cytometry after 48-h treatment of different concentrations of ACPS. The expression of pro-caspase-9, PARP, and p-p38 in SGC-7901 cells after treated by different concentrations of ACPS was detected using Western blot. The expression of pro-caspase-9, PARP, and p-p38 was detected after SGC-7901 cells were pre-treated by p38 specific inhibitor.
RESULTSCompared with the control group, the optical density of SGC-7901 cells decreased after treated by 1, 2.5, 5, and 10 mg/mL ACPS (P < 0.05). Meanwhile, the longer the acting time, the lower the optic density (P < 0.01). IC50 was 7.43 mg/mL at 24 h; 3.88 mg/mL at 48 h, and 1.32 mg/mL at 72 h respectively. ACPS suppressed the protein expression of pro-caspase-9 (P < 0.01) and up-regulated the expression of PARP (89KD) (both P < 0.01). Further study showed that the protein expression of p-p38 was up-regulated in SGC-7901 cells treated by ACPS of different concentrations at 24 h (P < 0.05). The expression of phosphorylation p38 and the ACPS induced apoptosis of SGC-7901 cells could be inhibited after treated by specific inhibitor for 2 h.
CONCLUSIONSACPS could inhibit the growth of SGC-7901 cells and induce apoptosis. The underlying mechanism of inducing apoptosis was partially due to activating the p38MAPK path and further activating Caspase9 and PARP, finally leading to cell death.
Actinidia ; chemistry ; Apoptosis ; drug effects ; Caspase 9 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; metabolism ; Polysaccharides ; pharmacology ; Stomach Neoplasms ; metabolism ; pathology ; p38 Mitogen-Activated Protein Kinases ; metabolism
4.Crossˉsectional analysis on relation between smoking and serum uric acid level
Bin TIAN ; Bing ZHANG ; Jimeng LI ; Yuhong GUAN ; Lan WEN
International Journal of Laboratory Medicine 2014;(24):3382-3384
Objective To understand the relation between smoking and serum uric acid level and to investigate whether the ser-um uric acid has the correlation with the gender,age and smoking history.Methods The data of the gender,age,blood uric acid in1 847 individuals aged 20-80 years with the healthy physical examination and without underlying diseases were performed the statisti-cal analysis.Results With male and female as the research objects,the serum uric acid level of smokers were higher than that of non-smokers and occasional smokers,the difference was statistically significant;the serum uric acid level had no statistically signifi-cant difference between smokers and occasional smokers;the serum uric acid level had no statistically significant difference among non-smoking,occasional smoking and smoking groups for males as the research objects alone;to divide the male subjects into groups according to age,the serum uric acid level of non-smokers,occasional smokers and smokers were not statistically significant among all age groups;serum uric acid level showed the increasing trend with the increase of smoking history,but there was no statistically significant difference.Conclusion The serum uric acid level of smokers is significantly higher than that of non-smokers and occa-sional smokers with male and female as the research objects;the difference in serum uric acid level between smokers and occasional smokers has no statistical significance;excluding the gender factor interference,the serum uric acid level of males is not affected by smoking or age;serum uric acid mean value demonstrates the increasing trend with the increase of smoking history.
5.Prognostic value of primary tumor site in early breast cancer patients with one to three positive axillary lymph nodes after radical surgery
Shaoqing NIU ; Ge WEN ; Yujing ZHANG ; Chengtao WANG ; Yiyang LI ; Xiaobo HUANG ; Xunxing GUAN ; Bixiu WEN
Chinese Journal of Radiation Oncology 2015;(5):506-510
Objective To explore the predictive value of primary tumor site for loco?regional recurrence ( LRR) in early breast cancer patients with one to three positive axillary lymph nodes after radical surgery. Methods The clinical data of 656 patients pathologically diagnosed with pT1?2 N1 M0 breast cancer who received radical surgery without postoperative radiotherapy in our hospital from 1998 to 2010 were retrospectively analyzed. In those patients, 156 had primary tumor located in the inner quadrant, 45 in the central quadrant, and 455 in the outer quadrant. LRR and local recurrence?free survival ( LRFS) were end points. The Kaplan?Meier method was used to estimate LRR and LRFS rates. The log?rank test was used for survival difference analysis and univariate prognostic analysis. Multivariate analysis was performed using the Cox regression model. Results The 5?and 10?year sample sizes were 416 and 191, respectively. The 5?and 10?year LRR rates were 8?6% and 12?9%, respectively, while the 5?and 10?year LRFS rates were 86?2%and 76?4%, respectively. The univariate analysis indicated that age, pT stage, Ki67 level, molecular classification, and primary tumor in the inner quadrant were significant influencing factors for LRR ( P=0?000,0?006,0?017,0?004,0?000). The multivariate analysis showed that age no greater than 35 years, primary tumor in the inner quadrant, and non?luminal subtype in molecular classification were independent prognostic factors for LRR and LRFS ( P=0?0012,0?012,0?005) . With an increasing number of risk factors ( ≥ 2 ) , patients with primary tumor in the inner quadrant had a dramatically increased LRR rate and a reduced LRFS rate, while patients with primary tumor in the outer or central quadrant kept the same LRR and LRFS rates. Conclusions The primary tumor site holds promise for prediction of LRR and LRFS in patients with pT1?2N1M0 breast cancer after radical surgery. Patients with primary tumor located in the inner quadrant have a high LRR rate and a low LRFS rate, which provides an excellent predictor for the risk of recurrence in patients with high?risk breast cancer.
6.Pharmacokinetics of salvianolic acid A after single intravenous administration in Rhesus monkey.
Jun-ke SONG ; Wen ZHANG ; Wei-ku ZHANG ; Zhang-ying FENG ; Tao XIE ; Guan-Hua DU
Acta Pharmaceutica Sinica 2015;50(9):1142-1147
Salvianolic acid A (Sal A) is one of the most effective compounds isolated from the root of Salvia miltiorrhiza. Up to now, several studies regarding the pharmacokinetic profiles of Sal A have been reported, however there is no such study reported in monkeys, the species which is more similar to human. The aim of this study is to develop a LC-MS method for the determination of Sal A in monkey plasma and apply it to the pharmacokinetic studies of monkeys. After single intravenous administration of Sal A, the plasma concentration-time curves were observed and the main pharmacokinetic parameters were calculated. The plasma concentration at 2 min (C2 (min)) values were (28.343 ± 6.426), (45.679 ± 12.301) and (113.293 ± 24.360) mg x L(-1) for Rhesus monkeys treated with Sal A at 2.5, 5 and 10 mg x kg(-1). The area under the concentration-time curve (AUC(0-∞)) values were (3.316 ± 0.871), (5.754 ± 2.150) and (13.761 ± 2.825) μg x L(-1) x h, respectively. Furthermore, this method was improved and applied to the simultaneous determination of Sal A, Sal B and Sal C, which provided useful information for preclinical studies and clinical trials of Sal A, Sal B and Sal C.
Administration, Intravenous
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Animals
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Caffeic Acids
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pharmacokinetics
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Chromatography, Liquid
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Drugs, Chinese Herbal
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pharmacokinetics
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Lactates
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pharmacokinetics
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Macaca mulatta
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Mass Spectrometry
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Plant Roots
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chemistry
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Salvia miltiorrhiza
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chemistry
7.Predictive value of molecular subtyping for loco-regional recurrence in early breast cancer patients with one to three positive axillary lymph nodes
Ge WEN ; Yujing ZHANG ; Yujia ZHU ; Xiaobo HUANG ; Jinshan ZHANG ; Fengyan LI ; Xunxing GUAN
Chinese Journal of Radiation Oncology 2013;(2):89-93
Objective To investigate the relationship between molecular subtypes of breast cancer and postoperative loco-regional recurrence (LR) in early breast cancer patients with 1-3 positive axillary lymph nodes (pN1) and to improve the individualized indications for post-mastectomy radiotherapy (PMRT)in these patients.Methods A total of 547 patients with pT1-2 N1M0 breast cancer,who received mastectomy between December 1998 and December 2009 in Sun Yat-sen University Cancer Center,were retrospectively analyzed.None of them received adjuvant radiotherapy after mastectomy.The patients were divided into luminal A group,luminal B group,HER-2-overexpressing group,and triple-negative group according to the molecular subtypes of breast cancer determined by immunohistochemistry and fluorescence in situ hybridization.The patients in different groups were compared in terms of LR rate (LRR) and LR-free survival (LRFS),and the risk factors for LR were analyzed in combination with clinical and pathological features.The Kaplan-Meier method was adopted to calculate LRR and LRFS;the Logrank test was used for survival difference analysis and univariate prognostic analysis.The Cox proportional hazards model was used for multivariate prognostic analysis.Results The luminal A group,luminal B group,HER-2-overexpressing group,and triple-negative group accounted for 30.0%,48.6%,9.3%,and 12.1%,respectively,of all the patients.The follow-up rate was 97.1% ;334 patients were followed up for at least 5 years,and 127 were followed up for at least 10 years.Univariate analysis showed that,compared with the luminal A group,the HER-2-overexpressing group and triple-negative group had significantly higher 5-year LRRs (19.0% vs 5.3%,x2 =4.28,P =0.026; 14.9% vs 5.3%,x2 =5.02,P =0.015) and significantly lower LRFSs (73.5% vs 91.1%,x2=7.27,P=0.005;80.6% vs 91.1%,x2=4.77,P=0.021).Multivariate analysis revealed that HER-2 overexpression,triple-negative phenotype,age of ≤ 35 years,and stage pT2 were poor prognostic factors for survival (LRR and LRFS) (x2 =2.29,2.08,18.22,and 6.86,P =0.020,0.016,0.001,and 0.005;x2 =1.90,1.41,8.58,and 3.94,P=0.006,0.025,0.002,and 0.039).The 10-year LRRs of patients with 0,1,and ≥2 of the above risk factors were 4.3%,14.1%,and 31.9%,respectively (x2 =28.03,P =0.000).Conclusions Molecular subtyping is helpful for individualized evaluation of LR risk in early breast cancer patients with 1-3 positive axillary lymph nodes (pN1).PMRT should be recommended for the patients with 2 or more risk factors for LR.
8.The characteristic analysis of the injured children under the age of 14 in Dongguan area
Jian GUAN ; Wenbing DENG ; Yi ZHANG ; Xuchang GUO ; Wen ZHANG ; Yanwen XIE
Chinese Journal of Emergency Medicine 2013;22(12):1408-1410
Objective To investigate the characteristics and risk factors of the injured children Under the age of 14 in Dongguan area and provide the basis for making the specific protective measures.Methods A retrospective analysis of 1707 clinical cases of the injured children in the emergency department of our hospital from 2006 to 2010.Results The incidence rate of child injury in Dongguan area is high,accounting for 3.25% of the emergency people at the same period.Fall-wound is at the first place of the causes of injury,accounting for 30.52% ; traffic accident injury and bums are in the second place,accounting for 19.22% and 11.42% ; the incidence rate of 7-10 years-old child injury is the highest,38.25% ; the incidence rate of boys injury is higher than girls; the incidence rate of the child injury of the children in these family such as their parents are separated,their mother are just senior high school graduates or the per capita monthly income for the whole family is less than RMB 3000 yuan is higher.There are 7 different degree of disability cases caused by injury and 10 death cases resulted from injury.Conclusions To carry out the pointed health education,average up the level of safety protection of parents and teachers,to strengthen the management of child injury surveillance and damage hazards,so as to minimize the occurrence of child injury.
9.Effects of Buyang Huanwu Decoction on L-type Calcium Channels of Cortical Neurons in Rats with Global Cerebral Ischemia and Reperfusion at Different Time Points
Li GUAN ; Fuman YAN ; Xiaodong ZHANG ; Wen SU ; Xiaoying LI ; Lequan ZHOU ; Rongjing LUO
Journal of Guangzhou University of Traditional Chinese Medicine 2001;0(03):-
【Objective】 The effect of pretreatment with Buyang Huanwu Decoction(BHD) on L-type calcium channels of cortical neurons in rats with global cerebral ischemia was observed,thus to explore the molecular therapeutic mechanism of BHD for cerebral ischemia as well as the pathogenic mechanism of Ca2+ message in ischemic injury of neurons.【Methods】SD rats were randomized into pseudo-operation group,model groups and BHD groups.And the model groups and BHD groups were divided into six groups according to the time points after reperfusion(2nd,12th,24th,48th and 72nd hour after reperfusion respectively).BHD groups received 0.64g/kg BHD by gastric infusion,bid,for 5 continuous days.Except the rats in pseudo-operation groups,the rats in other groups were induced global cerebral ischemia by modified Pulsinelli's four-vessel occlusion.Cerebral cortical neurons in rats were isolated promptly in 2nd,12th,24th,48th and 72nd hour after reperfusion.The recorded single-channel current was amplified by the EPC-9 patch-clamping amplifier,and then input into the computer by Pulse+Pulsefit.The analytical software TAC was used to detect the opening time and opening probability of the L-type Ca2+ channels in rats at different time points after reperfusion.【Results】In the model groups,the opening time of the L-type Ca2+ channels was prolonged after reperfusion as compared with that in the pseudo-operation group,and the opening probability of the L-type Ca2+ channels arrived at the peaks in 2nd and 24th hour after reperfusion.In BHD groups,the opening time in 72nd hour after reperfusion was decreased(P
10.Analysis of influencing factors for slow blood flow phenomenon after emergency percutaneous coronary intervention in patients with acute myocardial infarction
Liang GUO ; Haishan ZHANG ; Yuan GAO ; Qigang GUAN ; Wen TIAN ; Dalin JIA ; Yingxian SUN
Chinese Journal of cardiovascular Rehabilitation Medicine 2014;23(6):601-605
Objective: To explore the influencing factors of slow blood flow phenomenon after emergency percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Methods: Clinical and PCI angiographic data of 488 patients, who were diagnosed as AMI and received primary PCI in our hospital from Jan 2010 to Jun 2011, were retrospectively analyzed. Patients were divided into slow blood flow group (n=51, TIMI flow ≤ grade 2) and normal flow group (n=437, TIMI flow= grade 3). Their clinical characteristics between two groups were compared. Results: Compared with normal flow group, there were significant reductions in percentages of thrombus aspiration (75.3% vs. 60.8%) and application of platelet glycoprotein IIb/IIIa receptor antagonist (81.7% vs. 68.6%) during PCI, and significant rise in total length of implanted stents [(31.8±12.2) mm vs. (35.7±12.0) mm] in slow blood flow group, P<0.05 all. Multi-factor Logistic regression analysis indicated that percentages of thrombus aspiration during PCI and total length of stents were independent influencing factors for slow blood flow (P<0.05 both). Conclusion: Percentages of thrombus aspiration and total length of stents during PCI are independent influencing factors for slow blood flow.