1.Gene Polymorphism to the Effects of Low Level Aromatic Solvents Exposure on Spontaneous Abortion
Tongshan LIU ; Dafang CHEN ; Ping YANG
Journal of Environment and Health 1992;0(02):-
Objective To investigate the association between genetic polymorphisms of cytochrome P450 MSP1 gene and the glutathione s-transferase GSTM1 gene in female workers exposed to aromatic solvents and spontaneous abortion. Methods A retrospective epidemiological investigation was carried out among 276 female workers including 58 female workers with history of spontaneous abortion and 218 female workers without spontaneous abortion selected in Yanshan of Beijing by the trained investigators using the unified questionnaire. Results The spontaneous abortion of female workers was significantly associated with GSTM1 (absent) (OR=2.07, 95% CI: 1.15-3.71), but not MSP1 (present) and exposure to aromatic solvent. After adust-ment for major confounders including education, age, shift work, body mass index, passive smoking and occupational stress, the multiple logistic regression analysis showed that GSTM1 gene (absent) significantly increased the risk of spontaneous abortion of female workers (OR=2.15, 95% CI: 1.17-3.98). Before and after adjustment for major confounders including education, age, shift work, body mass index, passive smoking and occupational stess, the multiple regression analysis showed that GSTM1 (absent) combined with MSP1 (heterozygous variant type / homozygous variant type) significantly increased the risk of spontaneous abortion (OR=2.98, 95% CI:l. 17-7.59), using the group with GSTM1 (present) and MSP1 (homozygous wild type) as reference group. Conclusion Our data suggested a genetic influence on spontaneous abortion in this population, GSTM1 (absent) was significantly associaled with spontaneous abortion, also provide evidence of additional joint action of gene MSP1 (heterozygous variant type and homozygous variant type) and GSTM1 (absent) to spontaneous abortion.
2.Design and implementation of diabetes mellitus clinical database
Xiaoyu LIU ; Jianhong GAO ; Xiaodong LIU ; Dafang WU
Chinese Medical Equipment Journal 1993;0(05):-
Objective To design a clinical diabetes database based on the Diagnosing and Staging National Standards for diabetes mellitus and Microsoft Access.Method A clinical diabetes database was developed according to the diabetic patients' document in the 451st hospital of PLA from 1993 to 2004 with the development tool of Visual C++.Results The database had the function to save,add,search,modify and delete data,and could transfer data to Excel.Conclusion: The database is useful and practical.It is convenient to not only manage patient information but also to be beneficial for clinical diagnosis,treatment,teaching and research.
3.Design and application of health instruction database for diabetes mellitus patients
Xiaoyu LIU ; Jianhong GAO ; Xiaodong LIU ; Dafang WU
Chinese Medical Equipment Journal 1993;0(06):-
With Visual C++ as the development tool,a new health instruction database for diabetes mellitus patients based on Microsoft Access is designed.Users can store,insert,search,modify,delete the instruction data by it,and even can transfer the data to Excel.This database has high efficiency and great value.
4.Quantitative analysis of theophylline and its metabolites in urine of Chinese healthy subjects after oral administration of theophylline sustained-release tablets.
Ying LIU ; Yan ZHAN ; Yifan ZHANG ; Xiaoyan CHEN ; Dafang ZHONG
Acta Pharmaceutica Sinica 2014;49(7):1039-43
To study the metabolite excretion of theophylline, a rapid and specific method by liquid chromatography with heated electrospray ionization tandem mass spectrometry (LC-HESI/MS/MS) method for simultaneous determination of theophylline, 1, 3-dimethyluric acid (1,3-DMU), 3-methylxanthine (3-MX) and 1-methyluric acid (1-MU) in human urine was developed using theophylline-d6 and 5-fluorouracil as internal standards. Selected reaction monitoring (SRM) with heated electrospray ionization (HESI) was used in the negative mode for mass spectrometric detection. After diluted with methanol and centrifuged, the analytes and ISs were separated on a XDB-Phenyl (150 mm x 4.6 mm, 5 microm) column with a mixture of water-methanol-formic acid (30 : 70 : 0.15) as mobile phase at a flow rate of 0.6 mL x min(-1). The linear calibration curves for theophylline, 1, 3-DMU, 3-MX and 1-MU were obtained in the concentration range of 1.0-250 microg x mL(-1), separately. The method herein described is effective and convenient, and can be used for determination of theophylline and its three metabolites. The results showed that urinary excretion ratio of theophylline, 1,3-DMU, 3-MX and 1-MU is approximately 1 : 3 : 1 : 2 in Chinese subjects, which is similar to the reported excretion pattern in Caucasian.
5.Relativity study of thyroid hormone levels and depression mood in type 2 diabetes patients with insulin treatment
Dafang WU ; Jie LI ; Yan ZHOU ; Xiaoyu LIU
Chinese Journal of Behavioral Medicine and Brain Science 2011;20(1):32-34
Objective To observe the correlation of mood changes and serum levels of thyroid hormone in patients with diabetes and depression mood before and after intensive insulin therapy. Methods 340 patients with type 2 diabetes (T2DM) were enrolled, of which 187 cases were given intensive insulin therapy for 3 months and the other 153 cases were treated with oral hypoglycemic. All patients received depression measurement and tests of blood glucose, glycated hemoglobin (HbA1c), serum thyroid hormones before and after treatment. The data were analyzed statistically. During the treatment, fasting plasma glucose was controlled in ( 4.4 ~ 6. 1 )mmoL/L and 2-hour postprandial plasma glucose was controlled in (4.4 ~ 8.0) mmol/L. Results Thyroid hormone levels in the diabetic patients with depression mood ( T4 ( 6. 1 ± 1.4 ) μg/dl, T3 ( 0.98 ± 0.26) ng/ml ) were all lower than that in without depression mood ( T4 ( 8.4 ± 1.7 ) μg/dl, T3 ( 1.51 ± 0.29 ) ng/ml ) (P < 0. 01 ), and TSH ( 4.5 ± 1. 1 ) were higher than that in without depression mood ( 1.9 ± 0.9 ) uIU/ml (P < 0.01 ) before insulin treatment. After insulin therapy depression degree( 0.51 ± 0.12) were decreased significantly (0.68 ± 0. 21 )(P<0.01 ) ,and thyroid hormone levels were significantly increased (T3 (1.38 ± 0. 28 )ng/ml,T4 (7.7 ±1.5 )μg/dl ),and TSH levels were significantly reduced( (2.1 ± 1.2 ) uIU/ml) (P < 0. 01 ) than that before insulin therapy in the patients combined with depression mood. Depression degree was significantly negative correlated with T4 and T3 ( r= - 0.468, - 0.511, P < 0.05 ) and significantly positive correlated with TSH ( r = 0.583, P< 0.01 ) before treatment. Decline of depression degree were significantly positive correlated with elevation of T3, T4 levels ( r =0. 395 ,0. 337, P<0. 05 ) and were significantly negative correlated with decrease of TSH levels( r= -0. 239, P<0.05 ) after insulin treatment. However, depression degree and thyroid hormone levels did not significantly change before and after in oral antihyperglycemic agents groups. Conclusion Improvement of depression was associated with thyroid hormone levels in type 2 diabetic patients after insulin therapy.
6.Enantioselective determinination of R-warfarin/S-warfarin in human plasma using liquid chromatography-tandem mass spectrometry and its application in a drug-drug interaction study.
Shu JIN ; Yifan ZHANG ; Xiaoyan CHEN ; Ke LIU ; Dafang ZHONG
Acta Pharmaceutica Sinica 2012;47(1):105-9
To study the drug-drug interaction of morinidazole and warfarin and its application, a sensitive and rapid liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the determination of R-warfarin/S-warfarin in human plasma. In a random, two-period crossover study, 12 healthy volunteers received a single oral dose of 5 mg racemic warfarin in the absence and presence of morinidazole. Blood samples were collected according to a pre-designed time schedule. R-warfarin, S-warfarin and methyclothiazide were extracted with ethylether : methylenechloride (3 : 2), then separated on a Astec Chirobiotic V (150 mm x 4.6 mm ID, 5 microm) column using 5 mmol x L(-1) ammonium acetate (pH 4.0) - acetonitrile as mobile phase at a flow-rate of 1.5 mL x min(-1). The mobile phase was splitted and 0.5 mL x min(-1) was introduced into MS. A tandem mass spectrometer equipped with electrospray ionization source was used as detector and operated in the negative ion mode. Quantification was performed using multiple reaction monitoring (MRM). The resolution of warfarin enantiomers is 1.56. The linear calibration curves for R-warfarin and S-warfarin both were obtained in the concentration range of 5 - 1 000 ng x mL(-1). Intra- and inter-day relative standard deviation (RSD) for R-warfarin and S-warfarin over the entire concentration range across three validation runs was both less than 10%, and relative error (RE) ranged from -4.9% to 0.7%, separately. The method herein described is effective and convenient, and suitable for the study of metabolic interaction between morinidazole and warfarin. The results showed that coadministration of warfarin with morinidazole did not affect the pharmacokinetics of either R-warfarin or S-warfarin.
7.Protective effect of Shenfu soup on myocardial ischemia in rats and expression of apelin
Zhi LIU ; Jianquan WANG ; Xingyun WANG ; Chang LIU ; Lixue SHEN ; Huiying XU ; Dafang ZHANG
Chinese Pharmacological Bulletin 2015;(12):1760-1763
Aim To study the effects of Shenfu soup onthe ISO -induced myocardial ischemia injury model ofrats and the influence of apelin level changes on myocardial ischemia.Methods The myocardial ischemiainjury model of rats was established by the subcutaneous injection of ISO.For 1 5 days,rats in Shenfugroups were given by gavage 3,6 and 1 2 g · kg -1Shenfu soup and rats in SF injection group were given6.67 g·kg -1 Shenfu injection,rats in sham group andmodel group were given the same volume of distilledwater.Rats were subcutaneously multipoint injectedISO for 5 days on the eleventh administrating day.Theeffects of Shenfu soup on myocardial morphology,serum myocardial enzyme levels,apelin mRNA level inserum and apelin protein level in myocardial tissue,and relationship between myocardial enzyme and apelinexpression were evaluated. Results Shenfu soupcould reduce the degree of myocardial tissue necrosisand compared with model group,CK values and LDHvalues of rats in middleand highdose groups were significantly lower (P <0.05 or P <0.01 ).However,the apelin mRNA level in myocardial tissue and apelinprotein level in serum of the rats in middleand highdose groups compared with model group had increased(P <0.05,P <0.01 ).Meanwhile,serum levels ofapelin and the expression of myocardial enzyme CK andLDH were negatively correlated.Conclusion Shenfusoup has a protective effect on myocardial ischemia injury in rats induced by ISO and the mechanism is involved with the promotion of apelin mRNA and proteinexpression,the inhibition of myocardial enzyme production and the improvement of myocardial ischemia.
8.Effects of stable isotope labeled internal standard on determination of ivabradine and N-demethylivabradine in human plasma.
Dongqin LIU ; Jinghua YU ; Yifan ZHANG ; Dafang ZHONG ; Ling HE ; Xiaoyan CHEN
Acta Pharmaceutica Sinica 2015;50(3):348-54
This study aims to develop a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of ivabradine and N-demethylivabradine in human plasma, and investigate effects of stable isotope labeled (SIL) internal standard (IS) on ivabradine. The analytes and IS were extracted from plasma by protein precipitation with acetonitrile, and chromatographied on a Capcell PAK C18 (100 mm x 4.6 mm, 5 μm) column using a mobile phase of methanol and 5 mmol x L(-1) ammonium acetate. Multiple reaction monitoring with electrospray ionization (ESI) was used in the positive mode for mass spectrometric detection. The effect of ivabradine isotope peak [M+H+3] + on IS and the effect of SIL IS purity on ivabradine were evaluated. An appropriate concentration of SIL IS was chosen to permit method selectivity and linearity of the assay over the required range. The standard curves were demonstrated to be linear in the range of 0.100 to 60.0 ng x mL(-1) for ivabradine, and 0.050 0 to 20.0 ng x mL(-1) for N-demethylivabradine. The intra and inter day precision and accuracy were within the acceptable limits for all concentrations. Besides, the interaction between IS and ivabradine did not impact the determination of analytes. This method was successfully applied to a pharmacokinetic study of hydrogen sulfate ivabradine sustained release tablets on Chinese healthy volunteers.
9.CEA, CA19-9 in predicting the clinicopathologic characteristics and prognosis of primary duodenal carcinoma
Yijun LIU ; Wenyong XIE ; Shengmin ZHENG ; Dafang ZHANG ; Weihua ZHU ; Shu LI ; Xisheng LENG
Chinese Journal of General Surgery 2017;32(8):702-705
Objective To investigate the significance of tumor markers CEA and CA19-9 in predicting the clinicopathologic characteristics and prognosis of primary duodenal carcinoma.Methods A retrospective analysis of 110 cases with primary duodenal carcinoma treated in our hospital from January 1999 to December 2016 was conducted.ROC analysis,univariate and multivariate analysiswere performed to investigate the relationship between CEA,CA19-9 and the clinicopathologic characteristics of primary duodenal carcinoma.Kaplain-Meier method was used to analyze the relationship between CEA and CA19-9 and the prognosis of primary duodenal carcinoma.Results CEA level was of value for predicting the depth of infiltration,lymphatic involvement,metastasis and TNM stage.The receiver operating characteristic was 0.629,0.672,0.749,0.692 respectively.Univariate analysis showed serum CA19-9 lever was related to the depth of infiltration and serum CEA lever were related to tumor differentiation,lymphatic invasion,metastasis and TNM stage.Logistic analysis showed that CEA value was only associated with metastasis (OR:9.853,P < 0.01).Patients with elevated serum CEA level had a significant worse prognosis than patients with normal serum CEA level (P < 0.05).Conclusion Serum CEA level was closely associated with the clinicopathologic characteristics and prognosis of primary duodenal carcinoma.
10.Early predictive factors for intestinal necrosis in acute superior mesenteric artery occlusive diseases
Dafang LIU ; Xiaoqiang HAO ; Yingjiang YE ; Qiwei XIE ; Mujun YIN ; Xiaodong YANG ; Bin LIANG ; Shan WANG
Chinese Journal of General Surgery 2017;32(4):301-305
Objective To explore the early predictive factors of intestinal necrosis in patients with acute superior mesenteric arterial occlusive disease and its significance for the decision of exploratory laparotomy.Methods This retrospective study enrolled 29 patients diagnosed with acute superior mesenteric artery embolism or thrombosis in Peking University People's Hospital between July 1995 and June 2015.Results 12 patients developed intestinal necrosis.Patients with intestinal necrosis had a poorer prognosis than those who did not develop intestinal necrosis (x2 =14.867,P =0.000).In univariate analysis,the early predictive factors for intestinal necrosis were D-Dimer ≥ 600 μg/L (x2 =11.455,P =0.002),INR≥1.2 (x2 =3.948,P =0.047),pH values <7.4 (x2 =8.191,P =0.004),BE < -1.0 mmol/L (x2 =8.191,P =0.004),blood lactate ≥ 2.2 mmol/L(x2 =7.535,P =0.006),BUN ≥ 6 mmol/L (x2 =10.076,P =0.002),CK ≥ 80 U/L (x2 =8.191,P =0.004),LDH ≥ 210 U/L (x2 =13.079,P=0.000),AST ≥25 U/L (x2 =10.076,P =0.002),SIRS (x2 =10.076,P =0.002).Multivariate logistic regression analysis found no independent predictive factors of intestinal necrosis in patients with acute superior mesenteric arterial occlusive diseases.Conclusion Intestinal necrosis in acute mesenteric arterial occlusive diseases indicates a poor prognosis.Coagulation abnormalities,liver or kidney dysfunction,metabolic acidosis and SIRS necessitates an immediate exploration.