As a Chinese saying goes， "good Chinese medicinal material makes good medicine"， the traceability of Chinese medicinal materials is closely related to the high-quality development of Chinese medicine industry. This article intends to analyze the "new era of smarter food safety blueprint" and Proposed Rule for Food Traceability related to food traceability of the U.S. Food and Drug Administration （FDA）， including food traceability list， critical tracking events， and examples of exemptions. By studying the process and consideration of the construction of the FDA food traceability system， as well as the specific traceability requirements of fresh herbs， vegetables and fruits in the FDA food traceability system that are related to Chinese medicinal materials， on the one hand， it provides research materials for the communication and discussion of Chinese medicinal materials traceability， on the other hand， it also provides reference for the construction of food traceability system in China. To sort out the idea of constructing a traceability system for Chinese medicinal materials suitable for the current development status of traditional Chinese medicine， the contents to be considered are as follows：①To determine the traceability list of Chinese medicinal materials based on the risk control of Chinese medicinal materials. ②Determine the critical tracking links and information in the Chinese medicinal materials industry chain， and standardize the traceability information of Chinese medicinal materials. ③The quality information of Chinese medicinal materials should be reflected in the traceability of Chinese medicinal materials. ④Within the scope of the traceability list of Chinese medicinal materials， enterprises should be encouraged to make voluntary traceability by selecting Chinese medicinal materials with a good foundation of traceability work.

OBJECTIVETo research the role of lymph tracers to protect parathyroid in surgery for papillary thyroid carcinoma.

METHODSPatients with papillary thyroid carcinoma who met selected criteria were enrolled in this study. Patients were divided into carbon nanoparticle group, methylene blue group, and conventional surgery group.

RESULTSNo significant complication occurred in the patients of carbon nanoparticle and methylene blue groups. In carbon nanoparticle group, methylene blue group and conventional surgery group, the mean numbers of parathyroid glands detected during surgery were 3.1 ± 0.3, 2.9 ± 0.4 and 2.3 ± 0.3 (F = 3.78, P < 0.01) , the rates that parathyroid was cut mistakenly were 1.37% (2/146) , 2.62% (2/97) and 7.14% (6/84) respectively (χ(2) = 17.372, P < 0.05) ; and the incidence of postoperative hypocalcemia were 10.4% (5/48) , 9.1% (3/33) and 17.5% (7/40,χ(2) = 0.671, P = 0.037) .

CONCLUSIONThyroid lymphography technique is helpful to protect from the injury to the parathyroid glands in surgery.

Humans ; Hypocalcemia ; Lymphography ; Parathyroid Glands ; Thyroidectomy

Objective To detect the hepatotoxicity biomarkers using normal human hepatocyte (HepaRG) and high-content screening,and to combine the micronucleus test and single cell gel electrophoresis to estalish a rapid screening platform for in vitro cytotoxitity and genotoxicity.Methods The effects of rhubarb anthraquinones (AQs) on the reactive oxygen species (ROS),intracellular Ca2+ concentration and mitochondrial membrane potential (MMP) in HepaRG cells were studied using appropriate fluorescent probes Hoechst33342、DCFH-DA、Fluo4-AM、Mito Tracker Red CMX Ros and high-content screening methods,and the potential genotoxiciy triggered by AQs were analyzed using the high-content based cytokinesis block micronucleus test and high throughput comet assay.Results The intracellular ROS level of HepaRG cells was significantly elevated by a 24 h treatment with Emodin (25.0 μg/mL),aloe-emodin (25.0 μg/mL) or chrysophanol (50.0 μg/mL),which are dose-concentration dependent (P ＜ 0.05 and 0.01);the intracellular Ca2+ increased and mitochondrial damage were observed with the treatment of aloe-emodin (25.0 μg/mL) and rhein (50.0 μg/mL,P ＜ 0.05 and 0.01).Comparing to control group,Emodin (25.0 μg/mL) induced an increased micronucleus rate (1.59％ ± 0.68 ％,P ＜ 0.01) and significantly higher percentage tail DNA and Olive tail moment (respectively 10.155％ ± 2.17％ and 0.510 ± 0.06,P ＜ 0.05 and 0.01) after 24 h;while the chrysophanol increased the micronucleus rate to 1.29％ ± 0.54％ (P ＜ 0.01) after 72 h.Conelnsion The results on the cytotoxicities and genotoxicities of AQs are consistent with the literatures.In this study,a rapid screening model for both hepatotoxicity and genotoxicity was successfully established,which will help with the early screening during the drug development stage.

BACKGROUNDStem cell transplantation has been shown to have beneficial effects on dilated cardiomyopathy. However, mechanism for stem cell homing to cardiac tissue in dilated cardiomyopathy has not yet been elucidated.

METHODSMesenchymal stem cells were obtained from rat bone marrow, expanded in vitro, and labeled with (99m)Tc. Cardiomyopathy model was induced by doxorubicin in rats. (99m)Tc labeled cells were infused into the left ventricles in cardiomyopathy and control rats. Sixteen hours after injection, animals were sacrificed and different tissues were harvested to measure specific radioactivity. By use of real-time polymerase chain reaction and immunohistochemistry, mRNA and protein expressions for stromal-cell-derived factor 1 in cardiac tissue were measured.

RESULTSLabeling efficiency of mesenchymal stem cells was (70.0 ± 11.2)%. Sixteen hours after mesenchymal stem cell transplantation, the heart-to-muscle radioactivity ratio was increased significantly in cardiomyopathy hearts as compared to control hearts. Both mRNA and protein expressions of stromal-cell-derived factor 1 were up-regulated in cardiomyopathy hearts as compared with control hearts.

CONCLUSIONIn dilated cardiomyopathy induced by doxorubicin up-regulated expression of stromal-cell-derived factor 1 in heart may induce mesenchymal stem cells home to the heart.

Animals ; Bone Marrow Cells ; cytology ; metabolism ; Cardiomyopathy, Dilated ; therapy ; Cells, Cultured ; Chemokine CXCL12 ; genetics ; metabolism ; Immunohistochemistry ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo investigate the association between rs9722 polymorphisms in the S100B gene and hand, foot and mouth disease (HFMD) caused by enterovirus 71.

METHODSA total of 124 HFMD children with enterovirus 71 infection were enrolled as subjects, and 56 healthy children were enrolled as control group. The rs9722 polymorphisms in the S100B gene were detected for both groups, and the serum level of S100B protein was measured for 74 HFMD children.

RESULTSThe rs9722 locus of the S100B gene had three genotypes, CC, CT, and TT, and the genotype frequencies were in accordance with Hardy-Weinberg equilibrium. Compared with the control group, the HFMD group had significant increases in the frequencies of TT genotype and T allele (P<0.01). Children with severe HFMD caused by enterovirus 71 infection had significantly higher frequencies of TT genotype and T allele than those with moderate or mild HFMD (P<0.05). Compared with the cured patients, the patients with poor prognosis had significant increases in the frequencies of TT genotype and T allele in the rs9722 locus of the S100B gene (P<0.05). Among the 74 children with HFMD, the children with TT genotype had the highest serum level of S100B protein, and those with CC genotype had the lowest level (P<0.01).

CONCLUSIONST allele in the rs9722 locus of the S100B gene might be a risk factor for severe HFMD caused by enterovirus 71 infection.

Child, Preschool ; Enterovirus A, Human ; Enterovirus Infections ; complications ; Female ; Genotype ; Hand, Foot and Mouth Disease ; etiology ; genetics ; Humans ; Infant ; Male ; Polymorphism, Genetic ; S100 Calcium Binding Protein beta Subunit ; genetics

To evaluate the hepatotoxicity risks of physcion on the basis of the bilirubin metabolism mediated by glucuronidation of UDP-glucuronosyltransferases 1A1(UGT1A1 enzyme). The monomers were added into the rat liver microsomes to test the hepatotoxicity by using bilirubin as UGT1A1 enzyme substrate, with apparent inhibition constant K_i as the evaluation index. Liver microsome incubation in vitro was adopted to initiate phase Ⅱ metabolic reaction and investigate the inhibitory effect of physcion. Then the phase Ⅰ and Ⅱ metabolic reactions were initiated to investigate the comprehensive inhibition of metabolites and prototype components. The results showed that when only the phase Ⅱ reaction was initiated, physcion directly acted on the UGT1A1 enzyme in a prototype form, exhibited weak inhibition and the inhibition type was mixed inhibition; When the phase Ⅰ and Ⅱ reactions were initiated simultaneously, the inhibitory effects of physcion on UGT1A1 enzyme became strong and the inhibition type was mixed inhibition, suggesting that physcion had phase Ⅰ and Ⅱ metabolic processes, and the metabolites had strong inhibitory effect on UGT1A1 enzyme. This experiment preliminarily proved that the metabolites of physcion may be the main components to induce hepatotoxicity.
Animals ; Chemical and Drug Induced Liver Injury ; Emodin ; analogs & derivatives ; toxicity ; Glucuronosyltransferase ; metabolism ; Kinetics ; Microsomes, Liver ; drug effects ; Rats

The purpose of this study was to investigate the effect of apigenin on UGT1 A1 enzyme activity and to predict the potential drug-drug interaction of apigenin in clinical use. First,on the basis of previous experiments,the binding targets and binding strength of apigenin to UGT1 A1 enzyme were predicted by computer molecular docking method. Then the inhibitory effect of apigenin on UGT1 A1 enzyme was evaluated by in vitro human liver microsomal incubation system. Molecular docking results showed that apigenin was docked into the active region of UGT1 A1 enzyme protein F,consistent with the active region of bilirubin docking,with moderate affinity. Apigenin flavone mother nucleus mainly interacted with amino acid residues ILE343 and VAL345 to form hydrophobic binding Pi-Alkyl. At the same time,the hydroxyl group on the mother nucleus and the amino acid residue LYS346 formed an additional hydrogen bond,which increased the binding of the molecule to the protein. These results suggested that the flavonoid mother nucleus structure had a special structure binding to the enzyme protein UGT1 A1,and the introduction of hydroxyl groups into the mother nucleus can increase the binding ability. In vitro inhibition experiments showed that apigenin had a moderate inhibitory effect on UGT1 A1 enzyme in a way of competitive inhibition,which was consistent with the results of molecular docking. The results of two experiments showed that apigenin was the substrate of UGT1 A1 enzyme,which could inhibit the activity of UGT1 A1 enzyme competitively,and there was a risk of drug interaction between apigenin and UGT1 A1 enzyme substrate in clinical use.
Apigenin/chemistry* ; Bilirubin/chemistry* ; Drug Interactions ; Glucuronosyltransferase/metabolism* ; Humans ; Hydrogen Bonding ; Microsomes, Liver/drug effects* ; Molecular Docking Simulation

The bilirubin metabolism mediated by the phase Ⅱ metabolizing enzyme UGT1A1 in the liver was evaluated to study the potential hepatotoxicity risk based on investigation on the inhibitory effect of rhein and its metabolites on the UGT1A1 enzyme in Rhei Radix et Rhizoma. Firstly, in vitro liver microsomes incubation was used to initiate the phase Ⅱ metabolic reaction to investigate the inhibitory effect of rheinon UGT1A1 enzyme. Secondly, the phase Ⅰ and phase Ⅱ metabolic reactions were initiated to investigate the hepatotoxicity risk of rhein metabolites. It was found that the rhein and its phase Ⅱ metabolites had no significant inhibitory effect on UGT1A1 enzyme, but its phase Ⅰ metabolites significantly reduced UGT1A1 enzyme activity. Based on the metabolites analysis, it is speculated that the rhein phase Ⅰ metabolite rheinhydroxylate and its tautomers have certain hepatotoxicity risks, while the toxicity risk induced by the prototype and phase Ⅱ metabolites of rheinglucoside, rheinglucuronic acid and rhein sulfate is small.
Anthraquinones/toxicity* ; Chemical and Drug Induced Liver Injury ; Drugs, Chinese Herbal/toxicity* ; Glucuronosyltransferase/metabolism* ; Humans ; Liver/enzymology* ; Microsomes, Liver/drug effects* ; Rhizome

This study aims to establish an ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) method for the determination of emodin-8-O-β-D-glucoside(EG) and its metabolites in plasma, and to investigate the toxicokinetics(TK) behavior of them in rats. To be specific, the TK of EG and its metabolites from the first to the last administration in the repeated dose toxicity study was determined, and the kinetic parameters were calculated. The exposure of EG prototype and metabolites in rat plasma after oral administration of different doses of EG was evaluated. The result showed that the prototype of EG and its metabolites aloe-emodin-8-O-β-D-glucoside, emodin, aloe-emodin, and hydroxyemodin could be detected in rats after oral administration of high-, medium-, and low-dose EG. The area under the curve(AUC) of the prototype and metabolites after the first and last administration was in positive correlation with the dose. The time to the maximum concentration(T_(max)) of EG and metabolites in the three administration groups was <6 h, and the longest in vivo residence time was 12 h. The T_(max) and in vivo residence time of EG were prolonged with the increase in the dose. The metabolites emodin, aloe-emodin, and hydroxyemodin all had two peaks. Both hydroxyemodin and aloe-emodin exhibited increased plasma exposure, slow metabolism, and accumulation in vivo. In addition, aloe-emodin-8-O-β-D-glucoside and emodin disappeared with the increase in dose, suggesting the change of the metabolic pathway of EG in vivo in the case of high-dose administration. The mechanism of high-dose EG in vivo needs to be further explored. This study preliminarily elucidates the TK behavior of EG in rats, which is expected to support clinical drug use.
Animals ; Anthraquinones ; Chromatography, High Pressure Liquid/methods* ; Emodin/toxicity* ; Glucosides/toxicity* ; Mass Spectrometry ; Rats ; Toxicokinetics

In this study, we aimed to establish a rat liver micro-tissue evaluation system to evaluate the hepatotoxicity of the main monomers in Polygonum multiflorum. Rat primary hepatocytes were isolated and purified by two-step in situ perfusion method to prepare hepatic parenchymal cells. The ultra-low adsorption plate and the inverted model were used to establish an in vitro hepatotoxicity evaluation system. After the system was established, the main monomer components(monanthone with emodin type, rhein, emodin, emodin-8-O-β-D-glucopyranoside, physcion) of P. multiflorum were selected for in vitro hepatotoxicity evaluation. This study showed that the primary cells of the liver can form liver micro-tissues in the low adsorption plate method and the mold perfusion method, with good liver structure and function, which can be used to evaluate the hepatotoxicity of the drug to be tested after long-term administration. The five monomers to be tested in P. multiflorum can significantly affect the proliferation of primary liver micro-tissues in rats in a dose-and time-dependent manner. The hepatotoxic effects were as follows: monanthone with emodin type > rhein > emodin > emodin-8-O-β-D-glucopyranoside > physcion. The results suggested that the emodin-type monoterpene and rhein might be the potential hepatotoxic components, while the metabolites of emodin-8-O-β-D-glucoside and emodin methyl ether showed more toxic risks. The rat primary hepatocyte micro-tissue model system established in this experiment could be used to achieve long-term drug administration in vitro, which was consistent with the clinical features of liver injury caused by long-term use of P. multiflorum. The experimental results provided important information and reference on the clinical application and toxic component of P. multiflorum.
Animals ; Chemical and Drug Induced Liver Injury ; Emodin ; Fallopia multiflora ; Glucosides ; Plant Extracts ; Polygonum ; Rats