1.Metabolites of injected chlorogenic acid in rats.
Cen XIE ; Dafang ZHONG ; Xiaoyan CHEN
Acta Pharmaceutica Sinica 2011;46(1):88-95
Chlorogenic acid (5-CQA) is one of the major components in some Chinese herbal injections. However, the metabolism of 5-CQA in rats after intravenous injection has not been determined. An ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) method was applied to identify the metabolites in bile, urine, feces and plasma after a single intravenous administration of 10 mg x kg(-1) 5-CQA to rats. Using MSE and mass defect filter techniques, a total of 35 metabolites were detected in bile, urine, feces and plasma. The predominant metabolites in bile were glutathione conjugates of O-methyl-5-CQA, accounting for approximately 80% of the metabolites excreted in bile. The major components in urine were parent drug, O-methyl-5-CQA, hydrolyzed metabolites and glucuronide conjugates. The major components in feces were O-methyl-5-CQA and its cysteine conjugates. The major component in plasma was the parent drug. The urinary and fecal excretion pathways were equally important to 5-CQA in rats. These results demonstrate that 5-CQA undergoes extensively metabolism in rats and are highly reactive to nucleophiles such as GSH. This finding indicates that attention should be paid on the injections containing 5-CQA, which may covalently bind to proteins, leading to allergenic drug reactions.
2.Up-regulation of Nrf2 pathway and intervention of intracellular redox homeostasis in shikonin-induced A549 cell apoptosis
Chen XIE ; Hanying CHEN ; Jing ZHONG ; Xiaoqin WANG ; Bo ZHANG
Chinese Pharmacological Bulletin 2014;(10):1445-1451
Aim To investigate the roles of intracellu-lar reactive oxygen species ( ROS ) and Nrf2 pathway in shikonin-induced A549 cell apoptosis. Methods The cytotoxicity was analyzed by MTT assay. The ap-optosis of A549 cells was analyzed by both cellular morphological and biochemical methods. The relative changes of the redox marks ( ROS/GSH) were studied by fluorescence assay in the shikonin-treated A549 cells in accompany with the changes of the intracellular redox homeostasis by GSH/GSSG ratio. ROS inhibitor was also employed in the treatment to find the role of ROS in shikonin-induced A549 cell apoptosis. Real-time PCR analysis and ELISA assay were performed as well to determine the role of Nrf2 pathway in the shiko-nin-induced A549 cell apoptosis. Results The IC50 of shikonin on A549 cells was 3. 2 mg·L-1 . The cellu-lar redox homeostasis shifted toward oxidation signifi-cantly in shikonin treatment in a time-dependent man-ner. The expression of the Nrf2 pathway related genes was up-regulated by shikonin ( 3 . 2 mg · L-1 , 8 h ) . The expression of the anti-apoptotic genes was down-regulated , and proapoptotic genes were up-regulated by shikonin (3. 2 mg·L-1, 24h). Futhermore, the inhi-bition of intracellular ROS alleviated the cytotoxicity of shikonin in A549 cells. Conclusion The critical role of shikonin-induced redox imblance in A549 cell, coped with the secondary produced ROS and Nrf2 path-way antioxidants, result in A549 cell apoptosis.
3.Early death causes in 2349 patients who receiving heart valve replacement
Haisheng CHEN ; Shenghua LIU ; Zhimin ZHONG ; Cuixian XIE ; Qiuwei LIN
Chinese Journal of Thoracic and Cardiovascular Surgery 2010;26(3):151-153
Objective The early causes of death were analyze in 2349 patients who had undergone heart valve replacement.Methods Methods From January 1995 to December 2007,2349 patients with heart valve diseases received heart valve replacement.1109 cases were male and 1240 were female.The mean age of the patients was(41±19)years old.1962 cases had rheumatic heart valve disease,308 had congenital heart valve disease,39 had infective endocarditis,29 underwent reintervention by heart valve replacement,11 had Marfan syndrome.34 cases with coronary heart disease underwent heart valve prosthesis implantation and coronary artery bypass grafting.Mitral valve replacement(MVR)was performed in 1333 patients,aortic valve replacement(AVR)in 271,double valves replacement(DVR)in 736 and tricuspid valve replacement(TVR)in 9.There were 3075 mechanical valves and 10 bioprosthetic valves.Results From 1995 to 1999,death occurred in 16 of the 235 cases,early mortality rate was 6.81%.From 2000 to 2004,death occurred in 35 of the 1087 cases,early mortality rate was 3.22%.From 2005 to 2007,there were 29 deaths among 1027 cases,with an early mortality rate of 2.82%.Overall early mortality rate was 3.40%.The early mortality rate was 2.32%(31 in 1333 cases)in patients who underwent MVR,3.32% (9 in 271)in patients who underwent AVR,5.24%(40 in 736)in patients who underwent DVR,5.50%(7 in 127)with LVEDD≥70 mm,4.60%(14 in 304)with LVEF<0.40,2.14%(9 in 419)with NYHA class II,2.42%(37 in 1529)with NYHA class Ⅲ,and 8.48%(34 in 401)with NYHA class IV.The causes of 80 deaths were low cardiac output syndrome in 31 cases(38.8%),renal failure in 14 cases(17.5%),arrhythmia in 10 cases(12.5%),pulmonary infections in 8 cases (10.0%).cerebrovascular accidentin 5(6.3%),left ventricular rupture in 5(6.3%),multisystem and organ failure in 5(6.3%),and other cause in 2 cases(2.5%).Conclusion The causes of early death after heart valve replacement are low cardiac output syndrome,renal failure,arrhythmia,pulmonary infection,cerebrovascular accident,left ventricular rupture and multisystem and organ failure.
4.Effects of propofol on apoptosis in hippocampal neurons of fetal rats in vitro
Yuling ZHONG ; Yubing LIANG ; Li LI ; Jing CHEN ; Yubo XIE
Chinese Journal of Anesthesiology 2014;34(2):140-142
Objective To evaluate the effects of propofol on apoptosis in the hippocampal neurons of fetal rats in vitro.Methods The isolated hippocampal neurons were seeded into 96-well plates or 24-well plates at a density of 5 × 104 cells/ml.The cells were randomly divided into 5 groups (n =18 each) using a random number table:control group (group C),in tralipid group (group Ⅰ) and propofol 1,10,100 μmol/L groups (P1-3 groups).In group Ⅰ,10% intralipid was added to the culture media until the final concentration reached 100 μmol/L.In groups P1-3,propofol was added to the culture media until the final concentration reached 1,10 and 100 μmol/L,respectively,and the cells were then incubated for 3 h.The cell apoptosis was assessed by flow cytometry.The expression of Bcl-2 mRNA and caspase-3 mRNA was detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).The expression of Bcl-2 and actived-caspase-3 protein was determined by Western blot analysis.The apoptosis rate was calculated.Results Compared with group C,the apoptosis rate was significantly increased,the expression of Bcl-2 mRNA and protein was down-regulated,and the expression of caspase-3 mRNA and actived-caspase-3 protein was up-regulated in P1-3 groups (P < 0.05).There was no significant difference in the parameters mentioned above between group Ⅰ and group C (P > 0.05).Conclusion Propofol induces apoptosis in isolated hippocampal neurons by inhibiting Bcl-2 expression and enhancing caspase-3 activity in fetal rats.
5.New Method for Calibration the Output Power of Microwave Hyperthermia Apparatus
Nan JIANG ; Zhuying WANG ; Xiaolin CHEN ; Zhong XIE ; Wenke JIANG
Chinese Journal of Medical Physics 2009;26(6):1528-1530,1535
Objective: Nowadays, the power calibration methods of the microwave hyperthermia apparatus doesn't take the power loss of the radiator into account Aiming at this problem, the authors designed an equipment of measuring the actual output power of the microwave hyperthermia apparatus. A new method is proposed for calibration the output microwave power of microwave hyperthermia apparatus. Methods: The magnetron anode current was maintained at a default value by a control system. The microwave power generated by microwave source is coupled firstly to a low-power meter by the coaxial cable to measuring the power going through coaxial cable (P_(coaxial cable)). Then the microwave radiator is connected to the coaxial cable to make the microwave radiated by radiator. The radiator is assembled in the experimental device for the microwave completely absorbed by the water. The absorbed microwave energy of the water is calculated by measuring the water temperature change. The energy loss of the experimental device is calculated using the cooling rate. The output power of the radiator is equal to the ratio of the sum of the two aforementioned energy and the time. And the efficiency of the radiator η_(radiator), is equal to P_(radiator)/P_(coaxial cable) Results: The relationship between the actual output power of the microwave hyperthermia apparatus and the mag- netron anode current is P_(radiator) = 2η_(radiator) I. The efficiency of the radiator is η_(radiator)= (34±1)%. Conclusion: From the experimental results, the current method for calibration output power of microwave hyperthermia apparatus is defective, it dose not consider the conversion efficiency of radiator. Using the calibration method introduced in this paper, wecan accurately deter- mine the actual output power of microwave hyperthermia Apparatus.
6.Expression and clinical significance of annexin A1 in different stages of papillary thyriod carcinoma patients
Xuemei ZHONG ; Min CHEN ; Shishan DENG ; Shaoli XIE
Chongqing Medicine 2015;(25):3488-3490
Objective To explore the correlations between Annexin A1 protein expression and clinicopathological character-istics in carcinoma of papillary thyroid.Methods The different expressions of annexin A1 in papillary thyroid tissue and para-cari-noma tissue were investigated by immunohistochemistry.Results Among 69 samples tissues of papillary thyriod carcinoma,the positive rate of annexin A1 was higher than that of 69 para-carcinoma tissues(88.41%vs .8.69%),there was a significant difference (P <0.05).Furthermore,the expression of annexin A1 was correlation with the lymph node metastasis and tumor size,which was higher in ≥1 cm diameter of tumor(P <0.05).Conclusion High AnnexinA1 positive expression in papillary thyroid cancer tissues is associated with tumor malignant progression,which might be a valuable predictor and potential target for the diagnosis and treat-ment of papillary thyroid carcinoma.
7.Discussion of the system for full-period personnel cultivation of new nurses in Chinese medicine hospitals based on Fink curriculum construction
Yun CHEN ; Yufeng XIE ; Yinqin ZHONG ; Meixia YE
Chinese Journal of Practical Nursing 2017;33(18):1430-1433
Objective To build an efficient, scientific system for full-period personnel cultivation of new nurses in Chinese medicine hospitals. Methods This article used Fink curriculum model as the research method; used Broome′s classification theory of teaching goal as the theoretical guidance; used 'the training outline for new nurse (trying out)' issued by national health and family planning commission, the book 'the core competencies of nursing for traditional Chinese medicine', and cored competencies of nurses as the framework; used Delphi method and Analytic hierarchy process as research tools, so as to help the establishment of system for full-period personnel cultivation of new nurses in Chinese medicine hospitals. Results The preliminary exploration of system for full-period personnel cultivation of new nurses in Chinese medicine hospitals based on Fink curriculum, to make the system became more scientific, reasonable and comprehensive. Conclusions The system for full-period personnel cultivation of new nurses in Chinese medicine hospitals is feasible and creative, it can help to motivate the implementation of 'the training outline for new nurse (trying out)', to improve the quality of the nursing talents, to fasten the construction of nursing talents, to promote the development of nursing career.
8.Expression and clinical significance of stem cell marker Sox2 in human gastric cancer
Zhong CHEN ; Feng XIE ; Fengyun ZHONG ; Hong DU ; Yongmin YAN ; Hui QIAN
Tianjin Medical Journal 2016;44(5):548-551
Objective To detect the expression of stem cell marker Sox2 in gastric cancer (GC). Methods The mRNA and protein expressions of Sox2 in paired primary tumor tissues and their matching, adjacent non-cancerous tissues in a series of 60 cases of human GC were examined by reverse transcription-PCR (RT-PCR) and immunohistochemistry (IHC). χ2 test was used to analyze the correlation of Sox2 expression with clinicopathological parameters of GC tissues including age, gender, tumor size, histological type, TNM stage, differentiation degree, depth of invasion and lymph node metastasis. Results RT-PCR results showed that the positive rate of Sox2 expression was significantly increased in gastric tumor tissues (53.3%, 32/60) compared with that of matching, adjacent non-cancerous tissues (20.0%, 12/60, P<0.01). Semi-quantitative analysis showed that the relative intensity of Sox2 mRNA expression was significantly higher in gastric cancer tissues (0.724±0.209) than that in tissues adjacent to carcinoma (0.256±0.065,P<0.01). The positive expression of Sox2 was significantly higher in gastric tumor tissues (50.0%, 30/60) than that of matching, adjacent non-cancerous tissues (16.7%, 10/60,P<0.01). The positive expression of Sox2 was significantly higher in gastric tumor patients with TNM stage (Ⅲ+Ⅳ) than that of TNM stage (Ⅰ+Ⅱ). The positive expression of Sox2 was significantly higher in gastric tumor patients with low differentiation and undifferentiated tumor cells than that of patients with middle and high differented cells. The positive expression of Sox2 was also significantly higher in gastric tumor patients with the depth of invasion T3-T4 than that of patients with T1-T2. The positive expression of Sox2 was significantly higher in gastric tumor patients with lymph node metastasis than that of patients without lymph node metastasis (P<0.05 or P<0.01). Conclusion The elevated expression of Sox2 is associated with the initiation, invasion, progression, and metastasis of GC. Sox2 may serve as a novel diagnostic and therapeutic marker for human GC.
9.Clinicopathological features of IgA nephropathy associated with malignant hypertension and their correlation to renal vascular lesions
Pu CHEN ; Xiangmei CHEN ; Yuansheng XIE ; Guangyan CAI ; Xuefeng SUN ; Suozhu SHI ; Jie WU ; Zhong YIN
Chinese Journal of Nephrology 2008;24(6):392-397
Objective To explore the clinicopathological features of IgA nephrolpathy associated with malignant hypertension (IgAN-MHT) and to analyze their correlation with renal vascular lesions. Methods Twenty-nine patients of IgAN-MHT were screened from 2000 biopsy-proven eases with primary IgA nephropathy (IgAN) in our department from April 1997 to May 2007. Data of clinicopathology and follow-up of these 29 patients were collected. Semi- quantitative analysis was performed to evaluate the pathological changes. Inner lumen, outer lumen, intimal thickness, tunica media-to-internal lumen ratio of 436 arterioles, 124 interlobular arteries and 5 arcuate arteries were measured. The primary endpeint was the composite of a doubling of serum creatinine level and ESRD. Correlations of renal vascular lesions with clinical manifestation, pathological change and prognosis were examined by Spearman and Cox methods. Results 1.5% of all the IgAN patients presented malignant hypertension. The common clinical features were renal failure (100%), hyperurieacidemia (62.7%) and hypertriglyceridemia (51.7%). The average amount of urine protein excretion was 2.8 g/d. The common pathological changes were moderate mesangial proliferation, severe global sclerosis, severe interstitial inflammation and severe interstitial- tubular fibrosis. The small arteries (arcuate arteries and interlobular arteries) and arterioles (afferent arterioles) were both involved in IgAN-MHT. The characteristic lesions of intrarenal arteries included vascular occlusion, media thickening, proliferative endarteritis (onionskin lesion, musculomucoid intimal hyperplasia), hyaline arteriosclerosis, but mainly vascular occlusion (86.2%). The arteriole lesion was negatively correlated with age and total protein level; vascular occlusion was positively correlated with uric acid level. The average foUow-up period was 21.1 months. Forteen patients reached the endpoint. The arteriole lesion was the main independent risk factor for the progression of IgAN-MHT (RR=10.21, 95%CI=1.16~89.67). Conclusions The main clinical feature of IgAN-MHT is renal failure. The main histological feature of intrarenal vascular lesions is occludes arterioles. Arteriole lesion is the main independent risk factor for the progression of IgAN-MHT.
10.Clinical features of abnormal chromosome karyotypes in twin pregnancies complicated with structural abnormalities
Shilin ZHONG ; Qun FANG ; Baojiang CHEN ; Zhenyan HAN ; Yanmin LUO ; Jiansheng CHEN ; Yingjun XIE
Chinese Journal of Obstetrics and Gynecology 2011;46(9):649-654
ObjectiveTo investigate the clinical features of the abnormal chromosome karyotypes in twin pregnancies complicated with fetal malformations. Methods Totally 181 twin pregnancies (362 fetuses) in which one or two fetuses had abnormalities diagnosed by ultrasound were referred to the First Affiliated Hospital of Sun Yat-Sen University from January, 2000 to September, 2010. They were divided into different groups according to ( 1 ) maternal age: the cases with maternal age ≥35 were divided into advanced pregnancy group ( 105 fetuses) , and those with maternal age <35 were divided into young pregnancy group (203 fetuses) ; ( 2 ) conceived method : those conceived by assisted reproductive technology were divided into assisted reproductive group (81 fetuses), and the natural conception pregnancies were divided into natural conception group (227 fetuses) ; ( 3 ) chorionicity: the monochorionic twin (MCT) pregnancies were divided into MCT group( 123 fetuses), and the dichorionic twin (DCT) pregnancies were divided into DCT group( 185 fetuses); (4) structural abnormalities: 205 fetuses with structural abnormalities were divided into the abnormal fetal group, and 103 fetuses without structural abnormalities were divided into the normal fetal group. All fetuses were examined by the ultrasound and chromosomes were examined in 308 fetuses. Results( 1 ) The karyotype of fetuses: among 181 twin pregnancies, 23 cases had chromosomal abnormalities in 1 or 2 fetuses ( 12. 7% ,23/181 ), and chromosomes were exarmined in both fetuses in 20 of 23 cases. Twenty-six of 308 fetuses were found with abnormal chromosomes ( 8.4%, 26/308 ) , and the aneuploid was the most common type of abnormal karyotypes ( 53.8% , 14/26 ). Twenty-one of 205 fetuses with malformations were found with abnormal karyotypes (10. 2%, 21/205 ). (2) Seven of 123 fetuses in MCT group were with abnormal karyotypes (5.7%, 7/123), and 19 of 185 fetuses in DCT group were with abnormal karyotypes ( 10. 3%, 19/185 ). There was no statistical difference of abnormal chromosome incidence between the two groups. There were 14 fetuses with aneuploid in DCT group ( 7.6%, 14/185 ) ;but there was no fetus with aneuploid in MCT group. There was statistical difference between these two groups. In two cases of DCT group, only one fetus with malformation received chromosome examination because another fetus was dead, and the karyotypes were trisomy 21 and trisomy 18 respectively. Both fetuses of the rest 17 cases received chromosome examination, and the chromosomes of both fetuses in each pregnancy were different. Fifteen of 19 fetuses with abnormal chromosomes in DCT group were complicated with structural abnormalities, and 7 fetuses of 4 twin pregnancies in MCT group were with chromosomal abnormalities. (3) The comparison of the abnormal karyotype incidence between the advanced pregnancy group and young pregnancy group: the abnormal karyotype incidence of the advanced pregnancy group was 7. 6% (8/105), and that was 8.9% (18/203) in young pregnancy group. There was no statistical difference between the two groups ( P > 0. 05 ). Six of 105 fetuses in advanced pregnancy group were aneuploids (5. 7%, 6/105), and 8 of 203 fetuses in young pregnancy group were aneuploids (3.9%, 8/203). The aneuploid incidence in advanced pregnancy group was significantly higher than that in young pregnancy group ( P < 0. 05 ). (4) The comparison of the abnormal karyotype incidence between the assisted reproductive group and the natural conception group: 11 of 81 fetuses were with the abnormal karyotypes in assisted reproductive group ( 13. 6%, 11/81 ), and 15 of 227 fetuses were with the abnormal karyotypes in assisted reproductive group (6. 6%, 15/227). There was statistical difference between the two groups ( P <0. 05). There were 7 fetuses with the aneuploid in assisted reproductive group ( 8. 6%, 7/81 ) and 7 fetuses with the aneuploid in natural conception group ( 3. 1%, 7/227 ), which showed no statistical difference ( P >0. 05 ).(5) The comparison of the abnormal karyotype incidence between the abnormal fetal group and normal fetal group: 21 of 205 fetuses in abnormal fetal group were with abnormal karyotypes (10. 2%, 21/205), and 5 of 103 fetuses in normal fetal group were with abnormal karyotypes ( 4. 9%, 5/103 ) . There was no statistical difference (P > 0. 05 ). 13 fetuses in abnormal fetal group were with the aneuploid (6. 3%, 1 3/205), and only one fetus in normal fetal group was aneuploid (1.0%, 1/103 ). There was statistical difference between the two groups ( P < 0. 05 ). ConclusionsAneuploid is the most common abnormal karyotype in twin pregnancy complicated with fetal abnormalities, especially trisomy 21. Aneuploid mainly occurs in only one fetus of DCT, and chromosomal discordance is usually found in DCT. While in MCT, the twin fetuses with the same abnormal karyotype may have different pbenotypes. The results suggest that it is necessary to analyze both karyotypes of twins even if only one fetus is complicated with structural abnormalities.