Objective To explore the impacts of over-expression of microRNA-7 (miRNA-7) on the sensitivity of cis-platin in esophageal carcinoma cell line TE-1, and the possible mechanism thereof. Methods Lipofectmin 2000 method was used to transient transfect with miRNA-7 mimic into esophageal cancer cell line TE-1, which was taken as transfection group, mimic negative control was taken as transfection conrtol group. The expressions of miRNA-7 and epidermal growth factor receptor (EGFR) mRNA were detected by RT-PCR in the above two groups and normal control group. The total EGFR and EGFR in cytoplasmic and nucleus were detected with Western blot assay in transfection group and transfection control group. CCK-8 was used to detect IC50 of cisplatin in transfection group and transfection control group. The expression of EGFR was observed with immunofluorescence confocal microscope in two groups. Results The miRNA-7 expression was signifi-cantly increased in transfection group than that of transfection conrtol group and control group. The expression of EGFR mRNA was significantly reduced in transfection group (P<0.001). The total EGFR was significantly decreased in transfec-tion group than that of transfection conrtol group. The level of nuclear EGFR was significantly increased ( P<0.01),and cyto-plasm EGFR expression was significantly decreased in transfection group than that of transfection control group ( P<0.05). CCK-8 results showed that after the over expression of miRNA-7 in TE-1, the IC50 of cisplatin (48 h) increased in transfec-tion group than that of control group (P<0.01). Immunofluorescence results showed that EGFG in nuclear was higher in transfection group than that of transfection control group but its expressions reduced in cell membrane and cytoplasm. Con-clusion The over-expressed miRNA-7 in esophageal cancer cells TE-1 can reduce cisplatin sensitivity by the increased EGFR in nuclear translocation.

Population pharmacokinetics of vancomycin (VAN) in the Chinese patients was described by using nonlinear mixed-effects modeling (NONMEM). 619 VAN serum concentrations data from 260 patients including 177 males and 83 females were collected separately from two centers. A one-compartment model was used to describe this sparse data. No significant difference was observed between two center datasets by introducing SID covariate. The final model was as CL= (θ (base0+ θ(max) x(1 -e(-θ(Age)(Age/72) and V = θ x θ (Age)(Age/72). The creatinine clearance (CL(Cr)) and Age were identified as the most significant covariate in the final model. Typical values of clearance (CL) and volume of distribution (V) in the final model were 2.91 L x h(-1) and 54.76 L, respectively. Internal model validation by Bootstrap and NPDE were performed to evaluate the robustness and prediction of the final model. The median and 95% confidence intervals for the final model parameters were based on 1000 Bootstraps. External model evaluation was conducted using an independent dataset that consisted of 34 patients to predict model performance. Pharmacodynamic assessment for VAN by AUC (0-24 h) to MIC ratios of over 400 was considered to be the best to predict treatment outcomes for patients. AUC (0-24 h) was calculated by clearance based on the above population model. The results indicate that the conventional dosing regimen probably being suboptimal concentrations in aged patients. The approach via population pharmacokinetic of VAN combined with the relationship of MIC, Age, CL(Cr) and AUC(0-24 h)/MIC can predict the rational dose for attaining efficacy.
Aged ; Asian Continental Ancestry Group ; Female ; Humans ; Male ; Models, Biological ; Nonlinear Dynamics ; Vancomycin ; pharmacokinetics

Objective To investigate the profiles of resistance following continuous treatment with TM208 using pharmacokinetics/pharmacodynamic (PK/PD) model,as well as to characterize the estrogen levels in hibition in human breast cancer xenograft mice.Methods MCF-7 xenograftnudemice were given TM208 (150 mg · kg-1 · d-1) or vehicle orally for 18 days.The concentrations of estrogen were measured using the human estrogen ELISA kit.The pharmacokinetics and pharmacodynamics of TM208 were evaluated after administration.A one-compartment model with first order absorption was developed to describe the pharmacokinetics of TM208,and the time course of estrogen degradation was characterized by the indirect response model.Tolerance model was used to describe drug resistance of tumor.Results The simulation results showed that the inhibitory effects of TM208 on estrogen may decrease after continuous administration,and the KTO was 0.68 h-1 Conclusion The established PK/PD model allowed a better understanding of the role of estrogen inhibition in breast cancer treatment with TM208.Simulation based on the estrogen model allowed prediction of the detailed processes of TM208 effects on estrogen.Furthermore,the tolerance model-based modeling and simulation methods provided an option for the description and prediction of estrogen resistance.

OBJECTIVETo study the chemical constituents in seeds of Helicia nilagirica.

METHODThe ethanol extract was seperated by petroleum ether, dichloromethane, n-butanol in sequence, then isolated by silica gel column chromatography. The structures were identified and elucidated by physicochemical properties and spectral analysis.

RESULTFive compounds were isolated from the dichloromethane and n-butanol extracts, identified as p-hydroxybenzaldehyde (1), p-hydroxybenzoic acid (2), gallic acid (3), helicide (4), 4-formylpymyl-O-beta-D-glucopyranoside (5).

CONCLUSIONAll the compounds except IV were isolated from the plant for the first time. The compounds I, II and III were isolated from the genus Helicia for the first time.

Benzaldehydes ; chemistry ; isolation & purification ; Gallic Acid ; chemistry ; isolation & purification ; Molecular Structure ; Parabens ; chemistry ; isolation & purification ; Plants, Medicinal ; chemistry ; Proteaceae ; chemistry ; Seeds ; chemistry

AIM: To analyze the value of 24 - hour intraocular pressure ( IOP) monitoring in suspected glaucoma patients. METHODS: Totally 48 suspected glaucoma (96 eyes) were selected for 24 - hour IOP monitoring by using Accupen tonometer (24 - 3000) and non - contact tonometer (NCT, CT-80A) from 9 30 to 7 30 next day (once in 2h). During 07 30 to 21 30, patients were measured in sitting position,while during 23 30 to 05 30 in both sitting and supine position. RESULTS:A morning peak of IOP was shown at 7 30 in traditional position by using two measures with 22.05士3 608mmHg of NCT and 19.79士4.147mmHg of Accupen tonometer. The peak IOP in habitual position appeared in 5 30 with 21.64士4.814mmHg. The lowest IOP occurred in both position at 21 30 with 15. 73士3. 649mmHg. Both positions showed IOP trend of going up at night and then declining in the morning. CONCLUSION: The peak IOP in suspected glaucoma occurs mostly at early morning. Supine IOP of sleeping time is higher than that of sitting position.

Humans ; Moxibustion ; Depression ; Acupuncture Therapy ; Gastroesophageal Reflux ; Esophagitis, Peptic

The individual pathological and physiological characteristics of different patient population can significantly affect the pharmacokinetic (PK) behavior.Although the PK study results from healthy subjects play an important role in guiding clinical rational medication,they may not be necessarily applicable to the population of elderly,children and gravida,and may not be suitable for all morbid states.Therefore,this article will review the PK clinical studies of various special population.

Hemophilia is genetic bleeding disorder , and the replacement therapy by the infusion coagulation factors provides an available effective for hemophilia.With the drug development at home and abroad , signifi-cant progress has been achieved in the field of hemophilia treatment in recent years, including the design of long -acting clotting factor prepara-tions, gene therapy, and novel agents.This study provides a brief over-view of current therapies for hemophilia and reviews the latest develop-ments in its treatment.

OBJECTIVEThis study aimed to explore the impact of specimen collection and storage consumable products on trace element quantitative analysis.

METHODSDevices and consumable products of different brands used in specimen collection or storage were selected and treated separately as below:urine collection and storage tubes (Brand A, B, C and D, 2 samples for each brand) were treated with 1% of HNO(3) volume fraction for 2 - 4 h; blood taking device (Brand O, P and Q, 3 samples for each brand) were used for ultra-pure water samples collecting as simulation of blood sampling;dust sampling filters (Brand X, Y and Z, 2 samples for each brand) were cold digested by nitric acid for 12 h, followed by microwave digestion. Then cadmium, cobalt, chromium, copper, iron, manganese, molybdenum, nickel, lead, selenium, stannum, titanium, vanadium and zinc concentrations in the solutions obtained during the course of collect or storage were quantified by inductively coupled plasma mass spectrometer.

RESULTSFor the urine collection and storage consumable products, background values of elements were described as mean of parellel samples. The consentration of 14 quantified elements were relatively low for 5 ml cryogenic vials (brand B) with background values range of 0.001 - 0.350 ng/ml. The background values of copper of 50 ml centrifuge tubes (brand A), chromium of 5 ml cryogenic vials (brand C) and zinc of 1.5 ml centrifuge tubes (brand D) were relatively high, which were 1.900, 1.095 and 1.368 ng/ml, respectively. Background values of elements in blood sampling devices were described as x(-) ± s. Background values of chromium for brand O, P and Q were (0.120 ± 0.017), (0.337 ± 0.093) and (0.360 ± 0.035) ng/ml; for copper were (0.050 ± 0.001), (0.017 ± 0.012) and (0.103 ± 0.015) ng/ml; for lead were (0.057 ± 0.072), (0.183 ± 0.118) and (0.347 ± 0.006) ng/ml; for titanium were (7.883 ± 0.145), (8.863 ± 0.190) and (8.613 ± 0.274) ng/ml; zinc were (2.240 ± 0.573), (42.140 ± 22.756) and (8.850 ± 3.670) ng/ml. There were statistically differences of background values for chromium, copper, lead, titanium and zinc among the above three brands of blood sampling devices (all P values < 0.05). For air sampling filters, background values of elements were described as mean of parellel samples. Background values of chromium and nickel of sampling filters (brand X) were lowest, which were 17.000 and 15.400 ng per piece, respectively; while background values for other elements were relatively high, the quantification of cadmium, cobalt, copper, iron, manganese, molybdenum, lead, selenium, stannum, titanium, vanadium and zinc were 0.250, 0.550, 48.500, 690.000, 25.500, 0.900, 6.500, 10.550, 7.950, 10.500, 0.850, 370.000 ng per piece, respectively. Background values of chromium and nickel of sampling filters (brand Z) were highest, which were 171.000 and 29.850 ng per piece.

CONCLUSIONBackground values of trace elements varied among products of different brands, and the most noticable differences were found in chromium, manganese, nickel, lead, stannum and zinc.

Environmental Monitoring ; methods ; Quality Control ; Specimen Handling ; methods ; Trace Elements ; analysis

OBJECTIVETo investigate the risk factors of intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC).

METHODSThe clinicopathological data of 190 patients with cholangiocarcinomas (61 ICC and 129 ECC) diagnosed and treated in the Peking Union Medical College Hospital between 1998 and 2008 were collected. The clinicopathological data of 380 matched healthy controls were also collected. The information about liver diseases, family history, diabetes, smoking and drinking were recorded and analyzed.

RESULTSThe positive rate of HBsAg(+) and anti-HBc(+), HBsAg(-) and anti-HBc(+) and the incidence of choledocholithiasis or hepatolithiasis in ICC patients were 27.9%, 50.8% and 14.8%, respectively. The incidence of diabetes mellitus, cholecystolithiasis, choledocholithiasis or hepatolithiasis and previous cholecystectomy in ECC patients were 18.6%, 15.5%, 18.6% and 13.2%, respectively. The incidences of all above mentioned factors in the ICC or ECC patients were significantly higher than that in the controls (P < 0.05). Compared with the patients with ECC, the ICC patients had a significantly higher cirrhosis rate (P < 0.05).

CONCLUSIONOur study results show that choledocholithiasis or hepatolithiasis, liver cirrhosis and chronic HBV infection are possible risk factors for intrahepatic cholangiocarcinoma, while choledocholithiasis or hepatolithiasis, diabetes mellitus, cholecystolithiasis, history of cholecystectomy are risk factors for extrahepatic cholangiocarcinoma.

Bile Duct Neoplasms ; etiology ; virology ; Bile Ducts, Extrahepatic ; Bile Ducts, Intrahepatic ; Case-Control Studies ; Cholangiocarcinoma ; etiology ; virology ; Cholecystectomy ; Cholecystolithiasis ; complications ; Diabetes Complications ; complications ; Female ; Hepatitis B ; complications ; Hepatitis C ; complications ; Humans ; Liver Cirrhosis ; complications ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors