In recent years, more and more research shows that the pharmacokinetic parameter of traditional Chinese medicine can be affected by the disease states. It's possible that drug metabolic enzymes, transporters, cell membrane permeability and the change of microbes group could be interfered with physiological and pathological changes, which enables the pharmacokinetics of traditional Chinese medicine in the body to be altered, including the process of absorption, distribution, metabolism and excretion, and then the pharmacokinetic parameters of traditional chinese medicine are altered. It's found that investigating the pharmacokinetic of traditional Chinese medicine in the pathological state is more useful than that of in normal state because the great part of traditional Chinese medicine is mainly used to treat disease. This article reflects the latest research on the pharmacokinetic of traditional Chinese medicine in the disease state such as diabete, cerebral ischemia, liver injury, inflammatory disease, nervous system disorders and fever in order to provide certain reference for clinicians designing reasonable administration dose.
Animals ; Brain Ischemia ; drug therapy ; Chemical and Drug Induced Liver Injury ; drug therapy ; Humans ; Inflammation ; drug therapy ; Medicine, Chinese Traditional ; Nervous System Diseases ; drug therapy

Erythropoietin-producing hepatoma (EPH) receptors are considered the largest family of receptor tyrosine kinases and play key roles in physiological and pathologic processes in development and disease. EPH receptors are often overexpressed in human malignancies and are associated with poor prognosis. However, the functions of EPH receptors in epithelial-mesenchymal transition (EMT) remain largely unknown. This review depicts the relationship between EPH receptors and the EMT marker E-cadherin as well as the crosstalk between EPH receptors and the signaling pathways involved EMT. Further discussion is focused on the clinical significance of EPH receptors as candidates for targeting in cancer therapeutics. Finally, we summarize how targeted inhibition of both EPH receptors and EMT-related signaling pathways represents a novel strategy for cancer treatment.
Antineoplastic Agents ; Cadherins ; Epithelial-Mesenchymal Transition ; Humans ; Neoplasms ; Receptor Protein-Tyrosine Kinases ; Receptors, Eph Family ; physiology ; Signal Transduction

OBJECTIVETo explore the effect of down-regulation of insulin-like growth factor binding protein 7 (IGFBP7) on the proliferation and invasiveness of leukemia cell line U937 cells.

METHODSThree pairs of double-strand siRNA targeting IGFBP7 gene were transfected into SMMC7721 cells to select the most efficient one for U937 cells. qRT-PCR and Western blot were used to detect the expression of IGFBP7 in U937 cells after transiently transfected with siRNA of IGFBP7. Cell proliferation, adhesion, trans-endothelial migration and invasion were performed in transfected cells and control groups.

RESULTSAfter transfected with siRNA of IGFBP7 in U937 cells, the ability of cell proliferation was significantly decreased at 24 h (0.580 ± 0.159) compared to that of parental cells and scramble negative control (1.049 ± 0.274, 0.946 ± 0.195, respectively) (P < 0.01). Adhesion of U937 cells transfected with IGFBP7 gene specific siRNA to ECV304 cells was significantly lower than that of the control groups (0.247 ± 0.031 vs 0.406 ± 0.023 and 0.395 ± 0.011) (P < 0.01). Transendothelial membrane of U937 cells into the bottom of the 24-well plate for experimental group were less than those in the control groups \[(0.387 ± 0.021)×10(5) vs (1.017 ± 0.031)×10(5) and (0.908 ± 0.027)×10(5)\]. Cells adherent to the matrigel for experimental group were less than those in the control groups \[(0.197 ± 0.098)×10(5) vs (0.493 ± 0.067)×10(5) and (0.469 ± 0.083)×10(5)\]. The difference was significant (P < 0.01).

CONCLUSIONIGFBP7 gene plays a contributing role in leukemogenesis involving in leukemic cells' proliferation and interaction with endothelial cells through adhesion, invasion and migration.

Cell Proliferation ; Down-Regulation ; Humans ; Insulin-Like Growth Factor Binding Proteins ; genetics ; metabolism ; Leukemia, Myeloid, Acute ; metabolism ; pathology ; Transfection ; U937 Cells

OBJECTIVEDiagnosing neonatal asphyxia solely according to Apgar score may lead to misdiagnosis. The aim of this study was to explore new and more accurate diagnostic criteria for neonatal asphyxia.

METHODSTotally 10 376 live born neonates in our hospital were consecutively enrolled into the study. The following five items related to birth asphyxia, i.e., antepartum high-risk factors, Apgar scores, umbilical artery blood pH, organ injury, differential diagnosis on the causes of low Apgar score cases were examined and registered. The relationship among the first 4 items were analyzed. By differential diagnosis, the sensitivity and specificity of each index on diagnosing asphyxia and their complementary value on each other were investigated.

RESULTSThe items correlated well with each other (P < 0.01 or < 0.05) but were not entirely parallel and consistent; they could complement but could not substitute for each other. The sensitivity of antepartum high-risk factors, low Apgar scores, umbilical artery blood pH < 7.00 and organ injury was 100%, 100%, 44.44% and 100%, while the specificity was 17.99%, 98.90%, 96.05% and 96.62%, respectively. Of the 230 low Apgar score cases in this series only 50.9% coincided with asphyxia. For the 230 cases, when low Apgar score was combined with umbilical artery blood pH < 7.00, the sensitivity and specificity were 41% and 99.1% and when low Apgar score was combined with umbilical artery blood pH < 7.20, the sensitivity and specificity were 100% and 29.20%, respectively. After organ injury was added, the specificity was increased to 65.49%. When differential diagnosis was further added to exclude the other causes of low Apgar score cases, the misdiagnosis rate was minimized.

CONCLUSIONUp to now, no single accurate index for diagnosing neonatal asphyxia is available. In order to increase diagnostic bases and reduce misdiagnosis, the criteria of sole Apgar score should be replaced by multi-index diagnostic criteria. Based on the present study, a set of integrated diagnostic criteria for neonatal asphyxia is proposed: (1) prenatal high-risk factors, (2) low Apgar scores (respiratory depression must present), (3) umbilical artery blood pH < 7.00, if only pH < 7.20, the items (2) (4) (5) must be present, (4) hypoxic-ischemic organ injury (at least one organ dysfunction), (5) the other causes of low Apgar scores should be excluded. The last 4 indexes should all be met and the first one serves as reference. If multi-organ (three or more organs) dysfunction and (or) hypoxic-ischemic encephalopathy are present, severe asphyxia can be diagnosed.

Apgar Score ; Asphyxia Neonatorum ; blood ; diagnosis ; Diagnosis, Differential ; Diagnostic Errors ; prevention & control ; Humans ; Hydrogen-Ion Concentration ; Infant, Newborn ; Multiple Organ Failure ; Risk Factors ; Sensitivity and Specificity

OBJECTIVETo investigate the changes of the goblet cells in the intestine during the restitution process of the gut barrier after hemorrhagic shock.

METHODSForty-nine Sprague-Dawley rats with body weight of 250-300 g were divided into control group (n=7) and experimental group (n=42). Rats in the experimental group was further divided into 6 groups (n=7 each) according to different time point at 1, 3, 6, 12, 24, and 36 hours after hemorrhagic shock resuscitation. The specimens from ileum tissue were taken to observe the morphological chan ges of the intestinal mucosa. The number of goblet cells was determined by light microscope and/or electron microscope. The contents of trefoil factor family 3 (TFF3) of goblet cells were examined using GC-9A gas chromatographic instrument.

RESULTSAfter hemorrhagic shock, mucosal epithelial injury was obvious in the small intestine. Tissue restitution was found after 3 hours, and mostly established after 12 hours. Following tissue restitution,the denuded mucosal surface was covered intensively by goblet cells. The number of goblet cells on the intestinal mucosa was reduced significantly from 243+/- 13 at 1 h to 157+/- 9 at 24 h (r=- 0.910, P< 0.01), and returned to normal level at 36 h. In the experimental group, the content of TFF3 in the intestinal mucosa increased significantly at 12 hours, decreased, but was still higher at 24 hours (t=3.24, P< 0.05).

CONCLUSIONSThe goblet cells play a key role in the restitution of intestinal mucosa. High expression of TFF3 may facilitate the intestinal mucosal restitution in the early phase.

Animals ; Goblet Cells ; metabolism ; Ileum ; cytology ; Intestinal Mucosa ; cytology ; metabolism ; pathology ; Neuropeptides ; metabolism ; Rats ; Rats, Sprague-Dawley ; Shock, Hemorrhagic ; metabolism ; Trefoil Factor-3

A L9 (3(4)) orthogonal design table to be used to get nine combinations of extraction of three herbs of Wuji pill: Coptis chinensis, Tetradium ruticarpum and Paeonia lactiflora Pall., and nine extraction of single herbs correspondingly, altogether eighteen combinations. Quantification of five representative bioactive ingredients: berberine, palmatine, evodiamine, rutaecarpine, paeoniflorin in rat liver by ultra high liquid chromatography-tandem mass spectrometry after oral administration at 2 h time point of eighteen combinations. The result shows the bioactive ingredients have different concentrations betweem different combinations and the single herb with the same dosage significantly as well as the same dose combinations. C. chinensis with evodiamine concentration of low and high dose T. ruticarpum was positively correlated. T. ruticarpum with berberine concentration of low dose C. chinensis was negatively correlated and of meddle dose C. chinensis was correlated positively. T. ruticarpum with paeoniflorin concentration of middle dose P. lactiflora was correlated positively. P. lactiflora with palmatine concentration of middle dose C. chinensis was negatively correlated and with evodiamine and rutaecarpine concentration of middle dose T. ruticarpum was negatively correlated. These shows the three single herbs interactions resulted in the differences of each ingredients concentration in rat liver. The orthogonal analysis indicates the combination 12: 6: 6 make the maximum concentration in rat liver.
Administration, Oral ; Animals ; Biological Availability ; Biomedical Research ; methods ; Chromatography, High Pressure Liquid ; methods ; Drug Stability ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Liver ; metabolism ; Male ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; Temperature

BACKGROUNDAs with many studies carried out in European countries, a quality assurance program has been established by the National Center for Clinical Laboratories in China (NCCL). The results showed that the external quality assessment significantly improves laboratory performance for quantitative evaluation of hepatitis C virus (HCV) RNA.

METHODSSerum panels were delivered twice annually to the clinical laboratories which performed HCV RNA detection in China. Each panel made up of 5 coded samples. All laboratories were requested to carry out the detection within the required time period and report on testing results which contained qualitative and/or quantitative test findings, reagents used and relevant information about apparatus. All the positive samples were calibrated against the first International Standard for HCV RNA in a collaborative study and the range of comparison target value (TG) designated as +/- 0.5 log.

RESULTSThe numbers of laboratories reporting on qualitative testing results for the first and second time external quality assessment were 168 and 167 in the year of 2003 and increased to 209 and 233 in 2007; the numbers of laboratories reporting on quantitative testing results were 134 and 147 in 2003 and rose to 340 and 339 in 2007. Deviation between the mean value for quantitative results at home in 2003 and the target value was above 0.5 log, which was comparatively high. By 2007, the target value was close to the national average except for the low concentrated specimens (10(3) IU/ml). The percentage of results within the range of GM +/- 0.5 log(10) varied from 8.2% to 93.5%. Some laboratories had some difficulties in the exact quantification of the lowest (3.00 log IU/ml) as well as of the highest viral levels (6.37 log IU/ml) values, very near to the limits of the dynamic range of the assays.

CONCLUSIONSThe comparison of these results with the previous study confirms that a regular participation in external quality assessment (EQA) assures the achievement of a high proficiency level in the diagnosis of HCV infection. During the 5-year external quality assessment, sensitivity and accuracy of detection in most of the clinical laboratories have been evidently improved and the quality of kits has also been substantially improved.

Hepacivirus ; genetics ; Humans ; Laboratories ; standards ; Polymerase Chain Reaction ; Quality Control ; RNA, Viral ; analysis ; Reagent Kits, Diagnostic

A single dose of 3H-norcantharidin solution was intragastrically given, blood, tissues, urine and feces were collected as scheduled, and radioactivity in these samples was determined by tritium tracing method to investigate the pharmacokinetics, tissue distribution and excretion of norcantharidin in Kunming mice. The pharmacokinetic characteristics of norcantharidin were evaluated by DAS version 2.0. The blood concentration reached to maximum 0. 5 h after intragastric administration. The radioactivity in tissues was high in small intestine, gallbladder, stomach, adrenal gland, kidney, heart and uterus 15 minutes after administration, descending with time, and high in gallbladder, adrenal gland and uterus 3 hours post dosing. The 24 h accumulative excretion ratio of urine and feces were 65.40% and 1.33% respectively. 3H-norcantharidin was easily absorbed after orally given to mice, the radioactivity was high and existed for a long-time in gallbladder, adrenal gland and uterus, and low but also existed for a long-time in large intestine, thymus and fat tissue. 3H-norcantharidin was declined quickly in small intestine, stomach, kidney and heart, and occurred rarely in brain. Norcantharidin was excreted mainly by urinary route and seldom in feces, which may be the cause of the urinary stimulation side effects observed. Because the radioactivity measured were the sum of 3H labeled norcantharidin and its metabolites, further studies on the disposition of norcantharidin in mammal animals, on the separation or identification of metabolites and, if any, on their activities, are fairly needed.
Administration, Oral ; Animals ; Antineoplastic Agents ; administration & dosage ; chemistry ; pharmacokinetics ; urine ; Bridged Bicyclo Compounds, Heterocyclic ; administration & dosage ; chemistry ; pharmacokinetics ; urine ; Feces ; chemistry ; Female ; Male ; Mice ; Molecular Structure ; Random Allocation ; Tissue Distribution ; Tritium

The changes of microRNA expression in rat hippocampus after traumatic brain injury (TBI) were explored. Adult SD rats received a single controlled cortical impact injury, and the ipsilateral hippocampus was harvested for the subsequent microarray assay at three time points after TBI: 1st day, 3rd day and 5th day, respectively. We characterized the microRNA expression profile in rat hippocampus using the microRNA microarray analysis, and further verified microarray results of miR-142-3p and miR-221 using quantitative real-time PCR. Totally 205 microRNAs were identified and up-/down-regulated more than 1.5 times. There were significant changes in 17 microRNAs at all three time points post-TBI. The quantitative real-time PCR results of miR-142-3p and miR-221 indicated good consistency with the results of the microarray method. MicroRNAs altered at different time points post-TBI. MiR-142-3p and miR-221 may be used as potentially biological markers for TBI assessment in forensic practice.