Traditional Chinese ancient prescriptions have been used for treatment of liver cancer for a long history and the scientific and rational compatibility is a great wealth for modern research and development (R&D) of new drugs. The research and development of new drugs are often accompanied with a large investment, a long cycle and a high risk, especially for the anti-tumor drugs R&D which are facing more risks and lower successful rate. In this research, the regularity of compatibility of drugs was analyzed from 124 anti-hepatoma ancient prescriptions by computer program. The results can offer help to the R&D of anti-hepatoma new drugs and reduce the risk of drug screening. In addition, we surveyed 22 companies in this field from six provinces such as Beijing, Shanghai, Tianjin and so on and obtained 240 risk assessment questionaires. Then we used qualitative analysis method to interpret the greatest impacts for the risks in the process of R&D, production and sales of anti-hepatoma new drugs. The study provides a basis for anti-liver cancer drugs R&D researchers, who can take effective measures to reduce the R&D risks and improve successful rate.
Carcinoma, Hepatocellular ; drug therapy ; history ; China ; Drug Discovery ; history ; Drug Incompatibility ; Drug Prescriptions ; history ; Drugs, Chinese Herbal ; history ; therapeutic use ; History, Ancient ; Humans ; Liver Neoplasms ; drug therapy ; history ; Research ; history

Risk monitoring of new Chinese patent anti-hepatoma drugs is tracking recognized risks and residual risks, identifying emerging risk and ensure the implementation of the plan, estimating the process of reducing effectiveness. The paper is mainly through understanding the status of Chinese patent anti-hepatoma drugs, the content, characteristic and analysis method of dynamic risk monitoring, and then select the risk control indicators, collect risk information. Finally, puts forward the thought of anti-hepatoma drugs listed evaluation in our country, and try to establish the model of dynamic risk management of anti-hepatoma drugs.
Antineoplastic Agents, Phytogenic ; adverse effects ; economics ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; Drug Discovery ; economics ; legislation & jurisprudence ; organization & administration ; Drug and Narcotic Control ; economics ; legislation & jurisprudence ; organization & administration ; Drugs, Chinese Herbal ; adverse effects ; economics ; therapeutic use ; Humans ; Liver Neoplasms ; drug therapy ; Product Surveillance, Postmarketing

1H NMR metabonomics approach was used to reveal the chemical difference of urine between patients with Xiao-Chaihu Tang syndrome (XCHTS) and healthy participants (HP). The partial least square method was used to establish a model to distinguish the patients with Xiao-Chaihu-Tang syndrome from the healthy controls. Thirty-four endogenous metabolites were identified in the 1H NMR spectrum, and orthogonal partial least squares discriminant analysis showed the urine of patients with Xiao-Chaihu Tang syndrome and healthy participants could be separated clearly. It is indicated that the metabolic profiling of patients with Xiao-Chaihu Tang syndrome was changed obviously. Fifteen metabolites were found by S-pot of OPLS-DA and VIP value. The contents of leucine, formic acid, glycine, hippuric acid and uracil increased in the urine of patients, while threonine, 2-hydroxyisobutyrate, acetamide, 2-oxoglutarate, citric acid, dimethylamine, malonic acid, betaine, trimethylamine oxide, phenylacetyl glycine, and uridine decreased. These metabolites involve the intestinal microbial balance, energy metabolism and amino acid metabolism pathways, which is related with the major symptom of Xiao-Chaihu Tang syndrome. The patients with Xiao-Chaihu Tang syndrome could be identified and predicted correctly using the established partial least squares model. This study could be served as the basis for the accurate diagnostic and reasonable administration of Xiao-Chaihu-Tang syndrome.
Humans ; Least-Squares Analysis ; Medicine, Chinese Traditional ; Metabolome ; Metabolomics ; Proton Magnetic Resonance Spectroscopy ; Syndrome ; Urinalysis

4-coumarate coenzyme A ligase is a key enzyme of phenylpropanoid metabolic pathway in higher plant and may regulate the biosynthesis of ferulic acid in Angelica sinensis. In this study, the homology-based cloning and rapid amplification of cDNA ends (RACE) technique were used to clone a full length cDNA encoding 4-coumarate coenzyme A ligase gene (4CL), and then qRT-PCR was taken for analyzing 4CL gene expression levels in the root, stem and root tissue at different growth stages of seedlings of A. sinensis. The results showed that a full-length 4CL cDNA (1,815 bp) was obtained (GenBank accession number: KT880508) which shares an open reading frame (ORF) of 1 632 bp, encodes 544 amino acid polypeptides. We found 4CL gene was expressed in all tissues including leaf, stem and root of seedlings of A. sinensis. The expressions in the leave and stem were increased significantly with the growth of seedlings of A. sinensis (P < 0.05), while it in the root showed little change. It indicates a time-space pattern of 4CL gene expression in seedlings of A. sinensis. These findings will be useful for establishing an experiment basis for studying the structure and function of 4CL gene and elucidating mechanism of ferulic acid biosynthesis and space-time regulation in A. sinensis.
Amino Acid Sequence ; Angelica sinensis ; genetics ; Base Sequence ; Cloning, Molecular ; Coenzyme A Ligases ; genetics ; DNA, Complementary ; chemistry ; Molecular Sequence Data

AIMTo introduce the manufacture and use of a simple, new type of drop recorder of frog heart.

METHODSTo improve the perfusion device of (see text for symbol) and Straub method. Two electrodes of drop recorder were fixed in an injector of 20 ml. The input tube, output tube and resistance tube were all made of plastic material.

RESULTSThis device could be used to observe effects of preload, after-load, hormone and electrolyte on the cardiac output in isolated frog heart.

CONCLUSIONThe new type of drop recorder was economical and could be easily operated, it could be also connected to computer. Using the new type of drop recorder, effects of various physical and chemical factors on cardiac function could be observed directly, accurately.

Animals ; Electrodes ; Heart ; physiology ; Infusion Pumps ; Ranidae ; Weights and Measures ; instrumentation

Objective To investigate the carrying status and characteristics of Clostridium difficile isolated from infants.Methods Two hundred and thirty-eight stool specimens were collected from infant younger than 1 year old,that were hospitalized or outpatient from August to November 2015.Immunochromatography targeted GDH and toxin A&B of C.difficile was used for C.difficile screening,and those positive specimens were inoculated in CDIF and anaerobic culture.C.difficile isolates were genotyped by using slpA sequence typing (slpA ST),and tcdA,tcdB,cdtA and cdtB of C.difficile isolates were detected by PCR.Results Fifty C.difficile strains were isolated from 238 stool samples,and the isolated rates of C.difficile from <3 months,3 months to <6 months,and 6 months to 1 years old groups were 9.3%,17.6% and 27.3%(χ2=6.940,P=0.031<0.05),respectively.52.0%(26/50) of the C.difficile isolates were toxigenic,and 69.2% (18/26) toxigenic isolates harbored tcdA+tcdB+cdtA-cdtB-.Fifty C.difficile isolates were genotyped as 11 slpA STs,slpA ST fr-02 and kr-02 were the commonest genotypes in toxigenic C.difficile isolates;however,that was slpA ST xr-03 in non-toxigenic isolates.Conclusion High C.difficile carriage is found in infants younger than 1 year old,and more than half of C.difficile isolates are toxigenic.Most of toxigenic isolates harbored toxin A and B.The genotype of C.difficile isolates is different between toxigenic isolates and non-toxigenic isolates.

OBJECTIVEThe National Institutes of Health (NIH) category IIIa chronic prostatitis syndromes (non bacterial chronic prostatitis) were common disorders but with few effective therapies. Alpha-blockers and bioflavonoids had recently been reported in randomized controlled trials to improve the symptom of these disorders in a significant proportion of men. The aim of this study was to confirm these findings in a prospective randomized, placebo-controlled trial.

METHODSForty-five men with category IIIa chronic non bacterial protatitis were randomized into three groups as follows: (1) placebo; (2) phenoxybenzamine-hydrochloride:10 mg two times a day for one month; (3) flavoxate HCI-neptumus: 200 mg three times a day for one month. The NIH chronic prostatitis symptom score was used to grade symptoms at the beginning and conclusion of the study.

RESULTSAll the patients in three groups completed the study except three dropout patients in placebo group because of sever symptoms. The three groups were similar in age, duration of symptoms and initial symptom score. Patients taking placebo had a mean improvement in NIH-CPSI from 21.85 to 19.55 (not significant), while the phenoxybenzamine-hydrochloride group had a mean improvement from 21.95 to 13.75 (P < 0.01), and those taking flavoxate HCI-neptumus had a mean improvement from 21.75 to 16.95 (P < 0.05). The decrease in NIH-CPSI was associated with significant improvement in patients' clinical manifestations.

CONCLUSIONTherapy with alpha-blockers was well tolerated with significant symptomatic improvement in most men having chronic non-bacterial chronic protatitis while the bioflavonoids group had no significant improvement. Mechanism of both medicines needs further study.

Adrenergic alpha-Antagonists ; administration & dosage ; therapeutic use ; Adult ; Chronic Disease ; Flavonoids ; administration & dosage ; therapeutic use ; Flavoxate ; therapeutic use ; Humans ; Male ; Parasympatholytics ; therapeutic use ; Prospective Studies ; Prostatitis ; drug therapy ; Treatment Outcome

Objective To measure the level of microglia TRPC6 in mouse MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced neuroinflammation model and investigate its role in cytokine production and dopaminergic neuron damages. Methods Microglia were sorted by magnetic beads labeled with CD11b antibody and the level of TRPC6 in MPTP-induced neuroinflammation models was measured by western blotting. The proliferation of microglia and damages of dopaminergic neurons induced by MPTP were analyzed by immunofluorescence in CD11b-TRPC6 -/ - mice. Meanwhile, the expression of cryαB and cytokines in microglia was measured by western blotting and real-time quantitative PCR, respectively. Results The level of microglia TRPC6 in MPTP-induced neuroinflammation model was up-regulated. The expression of cryαB was increased and the cytokine level was down-regulated in the microglia in MPTP-injected CD11b-TRPC6 -/ - mice. Moreover, the dopaminergic neuron survival was improved in the MPTP-induced neuroinflammation model after TRPC6 knock-out in the microglia. Conclusions The expression of TRPC6 in microglia is up-regulated after MPTP injection, while in CD11b-TRPC6 -/ - mice the MPTP-induced cytokine expression is reduced, contributing to the improvement of dopaminergic neuron survival.

Objective To study mental characteristics of children with light lead poisoning. Methods Eighty - six children with light lead poisioning and 33 control children were evaluated with WISC - R and social adaptive capacity(SAB). Results 1. Intelligence quotient( IQ)and SAB of children with light lead poisoning were lower than normal children. 2. There was also deficiency of perception factor and memory/ concentration factor among children with lead poisioning and the blood lead level had negative association with perception factor. Conclusion Light lead poisioning may affect children's IQ, especially in the perception factor and memory /concentration factor.

OBJECTIVETo detect potential mutation in ALDH5A1 gene for a family affected with succinic semialdehyde dehydrogenase deficiency diagnosed by clinical inspection and urine screening.

METHODSPolymerase chain reaction and direct DNA sequencing were carried out for the affected child and her parents. Suspected ALDH5A1 gene mutations were verified in 100 healthy controls to exclude polymorphisms.

RESULTSThe child was found to have carried 2 heterozygous missense mutations in the coding region of ALDH5A1 gene, namely c.527G>A and c.691G>A, for which her mother and father were respectively heterozygotes. The same mutations were not detected in 100 healthy controls. The child was also found to have carried two previously described polymorphisms including a heterozygous c.545C>T(derived from her father) and a homozygous c.538C>T(derived from her mother).

CONCLUSIONMissense mutations of c.527G>A and c.691G>A in the ALDH5A1 gene are responsible for the pathogenesis of the disease in this family.

Adult ; Amino Acid Metabolism, Inborn Errors ; enzymology ; ethnology ; genetics ; Amino Acid Sequence ; Animals ; Asian Continental Ancestry Group ; ethnology ; genetics ; Base Sequence ; Child, Preschool ; China ; ethnology ; Developmental Disabilities ; Female ; Heterozygote ; Humans ; Male ; Molecular Sequence Data ; Mutation, Missense ; Pedigree ; Polymorphism, Genetic ; Succinate-Semialdehyde Dehydrogenase ; deficiency ; genetics