Objective To study the effect of purified water on the neurobehavioral development of the offspring and the synergistic effect of the magnesium deficiency in food. Methods SD rats were divided into four groups,control food plus control water (control group),control food plus purified water,magnesium deficiency food plus control water,magnesium deficiency plus purified water,from five weeks of age of the F0 generation to five weeks of the F1 generation respectively. Morris water maze (MWM) was used to test the spatial learning and memory ability of offspring of rats. Results In the early training days of the place navigation,control group offspring of rats showed a shorter swimming time than the other groups. There were no significant differences among all experimental groups in the later training days of the place navigation,spatial probe test and visible platform trial,however the tendency was still to remain. Conclusion Purified water can damage the learning ability of offspring of rats and the learning ability delay will be more obviously when magnesium is deficient in food.

Brown-Sequard Syndrome ; etiology ; Cervical Vertebrae ; Humans ; Intervertebral Disc Displacement ; complications ; surgery ; Male ; Middle Aged

Objective To investigate the correlation of hepatitis B patients in Fuzhou between resistance patterns in HBV P region and genotype,HBeAg,the hepatitis B process.Methods This was a retrospective study.The serum and clinic data of 1 115 hepatitis B patients were collected from the inpatient and outpatient Center for Liver Diseases in First Affiliated Hospital of Fujian Medical University between October 2011 and January 2015.HBV DNA was extracted and sequenced using the Sanger method to detect HBV genotype and resistance mutations in P region,HBeAg and HBeAb concentration were detected by chemiluminescent assay.The relationship between P region resistance mutations pattern,HBV genotype,serum HBeAg and the hepatitis B process was analyzed.The x2-test was used to compare the resistance rate and positive rate.Results There were significant differences between 14 kinds of resistance loci and the genotype distribution(x2 =30.788,P =0.004),the C/B genotype ratio of three common resistance loci (rtM204V/I,rtL180M,rtA181T/V) were 85/82,49/25 and 27/9,respectively,which in genotype C was higher than genotype B.The resistance ratio of hepatocellular carcinoma,liver cirrhosis,chronic hepatitis B,hepatitis B carriers was 31.4％ (11/35),37.6％ (65/173),27.3％ (146/535) and 21.8％ (43/197),respectively,which showed significant difference between the four clinical diagnosis (x2 =11.858,P =0.008).The highest percentage of resistance was liver cirrhosis,followed by hepatocellular carcinoma and chronic hepatitis B.There was significant difference in the distribution of HBV genotype between HBeAg (+) group and HBeAg (-) group (x2 =11.093,P =0.001),the HBeAg positive rate in genotype C [37.53％ (295/786)] was higher than in genotype B[35.62％ (280/786)].However,the total resistance rate between HBeAg (+) group and HBeAg(-) group was not significantly different[23.7％ (136/573) and 24.6％ (52/211),respectively,x2 =0.07,P =0.791].Conclusions HBV genotype was related to the resistance rates,HBeAg levels and the progress of hepatitis B.The resistance rate and HBeAg positive rate of genotype C were higher than those of genotype B,and clinical outcomes were worse in genotype C.HBV resistance rates and HBeAg levels were related to the progress of hepatitis B,the higher the resistance rates,the worse clinical outcomes.

Objective To investigate the consumption status of iodized salt and iodine nutrition status of Tianjin residents,and to provide a scientific basis for iodine supplementation.Methods Sampling methods:① Salt iodine:According to The National Project of Surveillance on IDD,the iodine in salt samples from 18 Tianjin districts (counties) was tested between 2002 to 2011.②Iodine nutritional status of children:Investigation of iodine nutritional status of children was conducted four times in 2002,2005,2009 and 2011.In 2002 and 2005,two primary schools were selected in each district.By age,gender parity principle,40 subjects aged from 8 to 10 in each school were randomly selected to perform thyroid examination and 20 of them were selected to collect urine samples for determination of urinary iodine.In 2009,according to their sub-area positions in the north,the south,the east,the west and the center of each district,5 primary schools were selected in each town (if there were less than five towns in the district,all towns had been selected).Twenty subjects aged from 8 to 10 in each school were selected to collect urine samples for determination of urinary iodine.In 2011,probability sampling method (PPS) was used to select 30 primary schools,and then 40 children aged from 8 to 10 were randomly selected in each school to examine thyroids.At the same time,urine samples from 12 children of the 40 selected children were tested.③Iodine nutritional status of women of childbearing age:In 2007,2008 and 2010,150,50 and 60 women of childbearing age were selected in Hangu District,urine samples of them were collected for determination of urinary iodine.④Iodine nutritional status of pregnant and lactating women:In 2011,3 towns around each primary school were selected.Five pregnant and five lactating women were selected in each town,urine samples of them were collected for determination of urinary iodine.Test methods:①Salt iodine was tested by direct titration,while Sichuan salt and other reinforced edible salt by arbitration determination based on the General Test Method in Salt Industry-Determination of Iodide Ion (GB/T 13025.7-1999).②Thyroid was tested by B-type-ultrasound and judged according to Diagnostic Criterion of Endemic Goiter (WS 276-2007).③Urinary iodine was tested by the Method for Determination of Iodine in Urine by As3+-Ce4+ Catalytic Spectrophotometry (WS/T 107-2006).Results From 2002 to 2011,the consumption rate of qualified iodized salt,the rate of qualified iodized salt,the coverage rate of iodized salt,the rate of non-iodinated salt was 92.7％(43 489/46 926),97.4％(43 489/44 694),95.1％ (44 694/46 926) and 4.8％(2273/46 926),respectively.The median salt iodine was in the range of 29.2-36.7 mg/kg.Children's urinary iodine was monitored 4 times,the median urinary iodine was 228.0,221.5,191.8; and 194.7 μg/L,respectively.Children goiter rates were 2.1％(27/1258),1.6％(19/1186) and 2.1％(26/1219) of the 3 times monitored.The median urinary iodine in pregnant and lactating women was 145.2 and 136.0 μg/L.The median urinary iodine in women of childbearing age was 130.7,196.1 and 229.5 μg/L,which increased with the increase of coverage of iodized salt.Conclusions The iodine nutrition of Tianjin residents,women of childbearing age and lactating women are at appropriate level.The iodine nutrition of pregnant women is lower than appropriate level.Recommended salt iodine level in our city is 30 mg/kg,or 25 mg/kg for ordinary residents,and 30 mg/kg for pregnant women.

CYP2D6 is an important drug-metabolizing enzyme. The polymorphism of CYP2D6 leads to metabolism difference and the different reactions of drugs in the individuals and different races are normal phenomenon in clinical medication. CYP2D6*10 is an important subtype in Asian people and 51.3% Chinese are classified with this subtype. To obtain recombinant active CYP2D6*1/CYP2D6*10 in baculovirus system by optimizing coexpression with CYPOR, and detect their activity to catalyze dextromethorphan, three recombinants pFastBac-CYP2D6*1, pFastBac-CYP2D6*10 and pFastBac-CYPOR were constructed and transformed into DH10Bac cell to obtain the recombinant Bacmid-CYPOR, Bacmid-CYP2D6*1 and Bacmid-CYP2D6*10. And then the recombinant CYP2D6*1 and CYP2D6*10 virus were obtained by transfecting Sf9. Then homogenate protein activity was determined with dextromethorphan as substrate. The multiple of infection (MOI) and its ratio of recombinant CYP2D6 virus to CYPOR virus were adjusted by detecting the activity of the homogenate protein. The Km and Vmax are 26.67 +/- 2.71 micromol x L(-1) (n=3) and 666.7 +/- 56.78 pmol x nmol(-1) (CYP2D6) x min(-1) (n=3) for CYP2D6*1 to catalyze dextromethaphan. The Km and Vmax are 111.36 +/- 10.89 micromol x L(-1) (n=3) and 222.2 +/- 20.12 pmol x nmol(-1) (CYP2D6) x min(-1) (n=3) for CYP2D6*10 to catalyze dextromethorphan. There is significant difference between CYP2D6*1 and CYP2D6*10 for Vmax and Km (P < 0.01). The clearance ratio of CYP2D6*1 is 25.0 and the clearance ratio of CYP2D6*10 is 2.0. The expressed CYP2D6*1 and CYP2D6*10 are useful tools to screen the metabolism profile of many xenobiotics and endobiotics in vitro, which are benefit to understand individual metabolism difference.
Animals ; Baculoviridae ; enzymology ; genetics ; Catalysis ; Cells, Cultured ; Chromatography, High Pressure Liquid ; methods ; Cytochrome P-450 CYP2D6 ; genetics ; metabolism ; Dextromethorphan ; metabolism ; Isoenzymes ; metabolism ; NADPH-Ferrihemoprotein Reductase ; genetics ; metabolism ; Plasmids ; Recombinant Proteins ; genetics ; metabolism ; Spectrometry, Mass, Electrospray Ionization ; Spodoptera ; cytology ; virology ; Transfection

OBJECTIVETo evaluate the relationship between plasma trough level of imatinib and clinical outcomes in Chinese CML patients.

METHODSPlasma trough levels in 416 CML patients who received imatinib orally in six general hospitals were assessed. The correlations of imatinib plasma trough level with baseline characteristics including age, weight and BSA, and clinical response were evaluated.

RESULTS(1) Effects of age, body weight and BSA on imatinib plasma trough levels were not to be clinically significant. (2) Median imatinib plasma trough levels was 1271 (109-4329). Imatinib plasma trough level was related to dose of imatinib administration. Plasma trough levels at imatinib of dose < 400, 400 and > 400 mg were (969 ± 585), (1341 ± 595) and (1740 ± 748) µg/L (P < 0.01), respectively. (3) There was no statistic difference in imatinib plasma trough level with complete cytogenetic response [CCyR (1337 ± 571) µg/L vs no CCyR (1354 ± 689) µg/L, P = 0.255]. (4) Imatinib plasma trough level might be important for a good clinical response in some CML patients.

CONCLUSIONThere was a large interpatient variability in imatinib plasma concentration in Chinese CML patients. No correlation of imatinib plasma trough level with CCyR was observed. However, higher doses of imatinib were shown to attain greater trough plasma concentration, suggesting that imatinib plasma trough level might be important for a good clinical response in some CML patients.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; Benzamides ; blood ; therapeutic use ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; blood ; drug therapy ; Male ; Middle Aged ; Piperazines ; blood ; therapeutic use ; Pyrimidines ; blood ; therapeutic use ; Treatment Outcome ; Young Adult

New Chemical Entities (NCEs) development is a systematic long-term project that involves multiple disciplines. The translation research will help to build an advanced R&D system from the basic laboratory research, preclinical studies and clinical evaluation to clinical application of drug, for the purpose of shortening the R&D cycle and accelerate the launch of new drugs. In new drug R&D and its clinical application, drug disposition (absorption, distribution, metabolism, excretion, ADME) properties are important criteria for assessing drug-likeness of candidates. ADME evaluation of NCEs plays an important role in the translation research throughout innovative drug R&D process. Therefore, ADME evaluation at the early stage of drug design and development will be helpful to improve the success rate and reduce costs, and further access to safe, effective drugs.
Absorption ; Biological Transport ; Drug Design ; Drug Evaluation, Preclinical ; Pharmaceutical Preparations ; chemistry ; metabolism ; Pharmacokinetics ; Tissue Distribution ; Translational Medical Research

Through summarization and analysis on etiology, pathology and acupoint selection in chapters about acupuncture in Shanghan Lun (Treatise on Febrile Diseases), written by ZHANG Zhong-jing, famous physician of the Eastern Han Dynasty, five features of acupuncture in the book are concluded: to cut off the pathway of pathogenic factors to prevent progress of diseases; to adopt both acupuncture and herbal medicine to give full play to their respective advantages in treatment; to distinguish pathogenesis carefully and select the proper acupoints; to observe the progressing tendency of diseases to give treatment accordingly; and to understand that yang channels are appropriate for acupuncture, while yin channels can also be selected in treatment. In this way, the law of acupuncture of ZHANG Zhong-jing is expected to be better understood.
Acupuncture Points ; Acupuncture Therapy ; China ; History, Ancient ; Humans ; Medicine in Literature

The specificity of the antigens and length of preservation time of erythrocytes are the interfering factors in blood group serological tests. In order to clarify the influence of preservation time of erythrocytes on the blood matching test, the titers of anti-D antibody were detected with papain method, BioVue cross matching card and DianaGel cross matching card in 7 series of panel red blood cells preserved for various length of time (0 to 9 months). The results showed that the titer of micro-column gel test (DianaGel card) was one tube higher than that of column agglutinating test (BioVue card). The titer of erythrocytes preserved for 9 months was as high as 256 tested by DianaGel card, but it was only 2 by papain method in the same anti-serum. It is suggested that there was no obvious difference between the results of micro-column gel test and column agglutinating test, and titer of papain method was the lowest.
Blood Grouping and Crossmatching ; Blood Preservation ; Erythrocytes ; immunology ; Humans ; Isoantibodies ; blood ; Rho(D) Immune Globulin ; Time Factors

OBJECTIVETo study the stereoselective glucuronidation of carvedilol (CARV) by three Chinese liver microsomes.

METHODSThe metabolites of CARV were identified by a hydrolysis reaction with beta-glucuronidase and HPLC-MS/MS. The enzyme kinetics for CARV enantiomers glucuronidation was determined by a reversed phase-high pressure liquid chromatography (RP-HPLC) assay using (S)-propafenone as internal standard after precolumn derivatization with 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosylisothiocyanate.

RESULTSTwo CARV glucuronides were found in three Chinese liver microsomes incubated with CARV. The non-linear regression analysis showed that the values of K(m) and V(max) for (S)-CARV and (R)-CARV enantiomers were (118+/-44) micromol/L, (2 500+/-833) pmol/(min.mg protein) and (24+/-7) micromol/L, (953+/-399) pmol/(min.mg protein), respectively.

CONCLUSIONThese results suggested that there was a significant (P<0.05) stereoselective glucuronidation of CARV enantiomers in three Chinese liver microsomes, which might partly explain the enantioselective pharmacokinetics of CARV.

Carbazoles ; metabolism ; China ; Glucuronic Acid ; metabolism ; Glucuronides ; metabolism ; Microsomes, Liver ; metabolism ; Propanolamines ; metabolism ; Stereoisomerism