1.The application of different GFR estimation equations in preoperative patients with renal cell carcinoma
Yan WU ; Hailan SHEN ; Yulei HOU ; Xiaoyun BI ; Huajian XU ; Biao XU ; Te CHEN
Chongqing Medicine 2017;46(8):1066-1069
Objective To evaluate the diagnostic performances of seven estimation formulas for glomerular filtration rate (GFR) in pre-operative patients with renal cell carcinoma.Methods A total of 386 pre-operative patients with renal cell carcinoma in the first affiliated hospital of Chongqing medical university from January 2012 to October 2014 were selected.All the patients' GFRs were measured by the renal dynamic imagingwith 99mTc-DTPA as reference (rGFR) and the seven GFR estimation equations (eGFR) were compared with the rGFR respectively.Their correlations and consistencies were observed with spearman correlation analysis and Bland and Altman analysis.The diagnostic sensitivity,specificity and likelihood ratios were calculated and the eGFR accuracies were assessed with receiver operator curve (ROC) analysis.Results The correlations between the rGFR and eGFRs were significantly (P<0.001).In addition,CKD-EPI-Asian Crea and Ruijin formula were more accurate than others in different stages with larger ROC area in diagnosing renal cell carcinoma.Conclusion There were significant correlations between the eGFRs and rGFR,but some deviations existed.CKD-EPI-Asian Crea and Ruijin formula were more suitable for assessment of eGFR of pre-operative patients with renal cell carcinoma.However,both of these equations had a few limitations.
2.Glucuronidation is the dominating in-vivo metabolism pathway of herbacetin:elucidation of herbacetin pharmacokinetics after intravenous and oral administration in rats
GE BEI-KANG ; ZHAO LIANG ; QI TE ; XU PING-XIANG ; XUE MING
Chinese Journal of Pharmacology and Toxicology 2017;31(10):1019-1019
OBJECTIVE To map a comprehensive metabolic pathway of herbacetin in rats, specifically, to elucidate the biotransformation of herbacetin in vivo and to simultaneously monitor the pharmacokinetic process of both parent drug and its major metabolites. METHODS liquid chromatography/ion trap mass spectrometry (LC/MSn) and ultra-liquid chromatography coupled with mass spectrometry (UPLC/MS) were combined in the current study for qualitative and quantitative determinations of herbacetin and its metabolites in bile, urine and feces after both oral and intravenous administration of herbacetin to rats. Enzyme kinetic studies on the intestinal and hepatic metabolism of herbacetin were further conducted to elucidate metabolic profiles of herbacetin in rat tissues and organs. Additionally, plasma concentration profiles of herbacetin and its metabolites in rats were obtained to characterize the overall pharmacokinetic behavior of herbacetin. RESULTS It was found that herbacetin was excreted primarily from rat urine in the form of glucuronide-conjugations. Subsequent in vitro enzyme kinetic studies and in vivo pharmacokinetic investigations suggested an extensive hepatic metabolism of herbacetin and the high exposure of herbacetin- glucuronides in systemic circulation. The clearance, half- life and bioavailability of herbacetin in rats were determined as (16.4±1.92)mL·kg-1·min-1, (11.9±2.7)min, and 1.32%, respectively. On basis of these findings, a comprehensive metabolic pathway of herbacetin in rats was composed. In addition, a physiology based pharmacokinetic (PBPK) model was successfully developed with the aid of the GastroPlus to simulate the pharmacokinetic process of herbacetin in rats. Application of the PBPK modeling can provide a useful starting point to understand and extrapolate pharmacokinetic parameters among different species, populations, and disease states. CONCLUSION After oral administration, herbacetin was subjected to colonic degradation and extensive first pass metabolism, with glucuronidation as its dominating in vivo metabolic pathway.
3.Mechanistic study on the pharmacokinetic process of salidroside in hypoxic rats
QI TE ; GE BEI-KANG ; ZHAO LIANG ; XU PING-XIANG ; XUE MING
Chinese Journal of Pharmacology and Toxicology 2017;31(10):996-997
OBJECTIVE To investigate the effect of hypoxia on the pharmacokinetic process of salidrosidein rats and to explore its underlying mechanisms. METHODS The Caco-2 cell monolayerwas exposed to 1% oxygen (O2) concentration for 24 h to build the hypoxiccell model. The transportation mode of salidroside was investigated with the aid of this hypoxia model by detecting the apparent permeability coefficient(Papp). Healthy Sprague Dawley (SD) rats were exposed to 9% O2 for 72 h for the construction of hypoxic rat model. Liver sample was subsequently collected from the hypoxic rats with an aim to identify enzymes responsible for salidroside metabolism. The expression levels of sali?droside-transporting and salidroside-metabolizing enzymes, including Sodium-dependent glucose cotrans?porters (SGLT1), β-glucosidase (GBA3)and sulfotransferase (SULT2A1), were thereafter detected by RT-PCR and Western blot. The metabolic activity of GBA3 and SULT2A1 was monitored by rat liver microsome incubation.In addition, the renal function of rats under hypoxia was assessed by detecting concentrations of blood urea nitrogen and creatinine. RESULTS The AUC and t1/2 values of salidroside in hypoxic rats were more than doubled, while the in vivo clearance was significantly reduced. Mechanistic study demonstrated that the PappA- B/PappB- A eualsto 10.3, indicating the potential active transport of salidrosile. The expression of SGLT1 and GBA3 was significantly decreased, which indicated a reduced metabolism of salidroside under hypoxia. Moreover, rat under hypoxia was found to suffer from renal dysfunction, with an abnormal value of blood urea nitrogen. CONCLUSION Due to the reduced metabolism and the abnormal renal function under hypoxia, the systemic exposure of salidroside in rats was signifi?cantly enhanced.
4.A correlation research between the Integrin alpha 2 (ITGA2)-807 C/T gene polymorphism and diabetic nephropathy
Xueling LIAO ; Junning CHEN ; Xiaoli LI ; Te DEGNG ; Yilan DENG ; Xu XIE
The Journal of Practical Medicine 2014;(16):2547-2550
Objective To explore the relation between the Integrin alpha 2 (ITGA2)-807 C/T gene and diabetic nephropathy (DN) in Han nationality in northern part of Guangxi. Methods 206 patients with type-2 diabetes were selected from the hospital. According to the diagnosis of diabetic nephropathy (DN) standards, 206 patients with type-2 diabetes were divided into diabetes without diabetic nephropathy (T2DM) and DN group, and 90 healthy people were selected as normal control (NC) group. The plasma lipid and lipoprotein levels were measured by routine method.And the genotypes and allele frequencies distribution were assessed by Polymerase chain reaction-restriction fragment length Polymorphism (PCR-RFLP). Results compared with the control group,plasma total cholesterol(TC),triglyceride(TG) and low density lipoprotein-cholesterol (LDL-C) levels in DN group blood were significantly higher (P < 0.05). ITGA2 gene - 807 - c/T genotype distribution and allele frequency in DN group were statistically significant (P<0.05). CT+TT genotypes and T allele frequency in DN group were significantly higher than control group (P<0.05).The relative risk for DN in subjects carrying T allele was 1.72 times of that in the C allele carriers(OR = 1.72, 95% CI = 1.72 ~ 2.517). And compared with control group and the DN group, ITGA2 gene-807-c/T genotype distribution and allele frequency differences in T2DM group had no statistical significance (P > 0.05). Conclusions The polymorphism of ITGA2-807C/T gene is associated with the development of DN in Han nationality in northern part of Guangxi. The T allele may be a genetic susceptibility genes for DN, which may promote the level of TC high expression and increase the risk of DN.
5.Analysis of risk factors for post-ERCP pancreatitis
Te XU ; Jing WANG ; Yunhong LI ; Yuling YAO ; Qibin HE ; Jun CAO ; Han WU ; Xiaoping ZOU
Chinese Journal of Digestive Endoscopy 2014;(9):503-507
Objective To investigate the risk factors of post-ERCP pancreatitis( PEP). Methods Data of 4,234 patients who underwent ERCP in Nanjing Drum Tower Hospital were retrospectively analysed. Information of patients and operations,including age,gender,operation history,major disease history,labora-tory examination before operation,abdominal ultrasound,CT,MRCP,detailed ERCP operation process,com-plications and treatment were carefully recorded. Then Chi-square test was used for univariate analysis,and stepwise multivariate Logistic regression for variate analysis. Linear correlations between risk factors were de-tected. Results There were totally 226 PEPs,with 5. 3% incidence rate. Univariate analysis showed that the female(χ2 =9. 715,P=0. 002),young( <60 years)(χ2 =6. 108,P=0. 013),chronic pancreatitis(χ2 =14. 703,P=0. 001),initial ERCP(χ2 =14. 899,P=0. 000),hypertension(χ2 =4. 489,P=0. 034),nor-mal bilirubin levels before operation(χ2 =19. 159,P =0. 000 ),difficult cannulation(χ2 =45. 824,P =0. 000),pancreatic guide wire(χ2 =30. 223,P=0. 000),papillary pre cut(χ2 =45. 928,P=0. 000),pan-creatography(χ2 =20. 170,P=0. 000)may be risk factors for PEP. Non conditional Logistic regression analy-sis showed that female(OR=1. 449,P=0. 011),initial ERCP(OR=1. 745,P=0. 003),normal bilirubin levels before operation(OR=1. 917,P=0. 000),difficult cannulation(OR=3. 317,P=0. 000)and pancre-atography(OR=1. 823,P=0. 004)were independent risk factors for PEP. Linear correlation analysis sugges-ted that pancreatic duct guide wire and papillary precut were related to the difficult cannulation,and the corre-lation coefficients were -0. 788 and -0. 699. Conclusion Female,young(<60 years),chronic pancreati-tis,initial ERCP,hypertension,normal bilirubin levels,difficult cannulation,pancreatic duct guide wire,pa-pillary precut,pancreatography may induce PEP. Female,normal bilirubin levels before operation,initial ER-CP,difficult cannulation and pancreatography are independent risk factors for PEP,while pancreatic duct guide wire,papillary precut are not,as they were linear correlated to difficult cannulation.
7.The effect of thyrotropin receptor antibodies on the proliferation of FRTL-5 cells and the expression of protooncogene c-fos mRNA
Peihua FANG ; Mei LÜ ; Weidong ZHOU ; Jianmin LI ; Bingrei XU ; Te TANG ; Yubin TAN
Chinese Medical Journal 1998;111(5):412-415
Objective Hyperthyroidism and a diffuse goiter are the main symptoms of Graves' disease (GD) associated with autoantibodies to thyroid-stimulating hormone (TSH) receptor (TRAb). The present study was conducted to evaluate effects of autoantibodies in patients with GD (TRAb-IgG) on induction of the proliferation and c-fos mRNA expression in FRTL-5 cells (Fisher rat thyroid cell line).Methods Highly purified IgG fractions were isolated from 11 patients with GD, TRAb-IgG and 15 normal individuals (normal controls) with Protein A Sepharose CL-4B affinity column chromatograph. FRTL-5 cells, which had been grown to subconfluency and deprived of TSH for a few days. Then, these cells were used for measuring cAMP content, 3H-thymidine incorporation in cells and the expression of c-fos mRNA respectively.Results After stimulation of TRAb-IgG, the cAMP production and 3 H-thymidine incorporation in FRTL-5 cells were much higher than those from normal controls (P<0.05 respectively). Using 32P labelled v-fos probe by the Northern Blot method, the expression of c-fos mRNA could be induced by IgGs from patients with GD.Conclusions These data suggest that the stimulation of TRAb-IgG followed by cAMP production and 3H-thymidine incorporation is related to the induction of c-fos mRNA and, thus, to the growth of FRTL-5 cells.
8.Research advances in susceptibility genes of non-alcoholic fatty liver disease and its association with type 2 diabetes
Journal of China Pharmaceutical University 2018;49(5):537-544
Nonalcoholic fatty liver disease(NAFLD)as the most common hepatic disease worldwide is affected not only by extrinsic factors, but also by genetic ones. Type 2 diabetes mellitus(T2DM), another chronic disease regulated by both environmental and genetic factors, is closely related to NAFLD in signal pathways and susceptibility genes. This review summarizes the susceptibility genes of NAFLD, especially points out their relevance to T2DM and suggests their related clinical applications, which provide further evidence for the exploration of the mechanisms of the two diseases with a new direction for their diagnosis and treatment.
9.Diagnostic value of GP73, AFP and AFU combined detection in early hepatocelluar carcinoma
Te CHEN ; Xiaoyun BI ; Huajian XU ; Hailan SHEN ; Yulei HOU ; Detao LI ; Liping ZHANG ; Yan WU
Chongqing Medicine 2017;46(35):4923-4926,4929
Objective To evaluate the diagnostic value of combination detection of alpha-fetoprotein (AFP),Golgi protein 73 (GP73) and a-L-fucosidase (AFU) for early hepatocellular carcinoma (HCC).Methods A total of 222 patients with liver diseases in this hospital from March 2016 to March 2017 were collected and divided into the early stage HCC group (74 cases),late stage HCC group (27 cases),liver cirrhosis group (74 cases) and chronic hepatitis B group (47 cases),and contemporaneous 49 individuals undergoing physical examination were selected as the healthy control group.The levels of serum GP73,AFP and AFU were detected in each group.The ROC curve was drawn.The diagnostic values of single detection and combined detection of 3 indicators for diagnosing early HCC were evaluated.Results The serum GP73,AFP and AFU levels in the early stage HCC group were significantly higher than those in the liver cirrhosis group,chronic hepatitis B group and healthy control group (P<0.05).In the HCC screening,the area under the curve (AUC) of AFP ROC curve for singly diagnosing HCC was 0.910(95%CI:0.864-0.936),AUC of GP73 and AFP combined diagnosis was maximal [0.925 (95% CI:0.889-0.950)] and the sensitivity was the highest (95.0%).In the differentiation diagnosis between early HCC and liver cirrhosis,AUC of GP73 for single diagnosis was maximal [0.842(95%CI:0.746-0.879)] and the specificity was the highest (86.5%);AUC of GP73 and AFU combined diagnosis was maximal[0.901(95%CI:0.788-0.907)].Conclusion GP73 and AFP for combined detection of HCC can increase the diagnostic efficiency of HCC screening.GP73 and AFU combined diagnosis can increase the diagnosis efficiency of early HCC,which has an important significance for the differentiation diagnosis between early HCC and liver cirrhosis.
10.Expression level and clinical significance of FSTL1 in serum of patients with acute coronary syndrome
Te CHEN ; Xiaoyun BI ; Huajian XU ; Yulei HOU ; Hailan SHEN ; Detao LI ; Liping ZHANG ; Yan WU
International Journal of Laboratory Medicine 2018;39(8):942-946
Objective To observe the level changes and clinical diagnostic value of follicular statin -1 (FSTL1)in the serum of patients with different types of acute coronary syndrome(ACS).Methods Collected the clinical diagnosis of acute coronary syndrome patients 98 cases,which contained ST segment elevation my-ocardial infarction(STEMI)in 34 cases,non ST elevation myocardial infarction(NSTEMI)in 28 cases,unsta-ble angina pectoris(UA)in 36 cases,while the examination resuLts of healthy people as a control group of 20 cases.The Venous blood was collected and the FSTL1 levels of the 4 groups were detected by ELISA.Results The levels of Serum FSTL1 in ACS group was significantly higher than that in normal control group(P<0.05).Serum FSTL1 of the ACS group were significant correlated with Gensini score,cTNT,hs-CRP(related coefficient:0.210,0.236,0.219 separately).The AUC of FSTL1 was 0.910(95% CI:0.832 -0.988),which was lower than cTNT.The best cut-off value of FSTL1 as a biomarker was 5.65 μg/L(specificity:84.2% and sensitivity:77.5%).Moreover the combination of FSTL1,HDL and cTNT exhibited significantly higher AUC=0.945(95% CI:0.909 -0.981)than did other biomarkers alone or pair combinations.Conclusion In pa-tients with acute coronary syndrome,serum FSTL1 levels has a positive correlation with the degree of coro-nary stenosis and inflammation reaction,and has certain value in the diagnosis of acute coronary syndrome.