OBJECTIVE: Analyze the applications and challenges of guidelines for pharmacoeconomic evaluation (PE) in China. METHODS: Reviewing what Chinese health policy need from pharmacoeconomics; analyzethe applications and challenges of guidelines for PE in China; summarize the application and development of the guidelines for PE in the world. RESULTS: PE plays an important role in Drug development, pricing, reimbursement and evidenc-based clinical pathway. Since PE guidelineis not mandatory in healthcare policy decision making in China, and there are lack of high-quality, reliable database for PE, the guideline encountered many difficulties and challenges in practice and hasn't play its due role yet. CONCLUSION: Based on the experience from other counties and practical in China, we recommended that PEguideline shouldbe mandatory. It is recommended to set up national research institutions for PE, and update or supplementthe guidelines regularly. Moreover, the basic research should be strengthened, such as rational drug use, pharmacoepidemiology, quality of life.

In this paper, the RP-HPLC specific chromatography was adopted, with DIKMA-C18 (4.6 mm x 250 mm, 5 µm) as the chromatographic column, with a gradient elution compose of acetonitrile and 0.1% phosphoric acid at flow rate of 0.8 mL · min(-1), the detection wavelength was 220 nm. The difference of the HPLC specific chromatograms between the Lu Dangshen and other different base sources and different producing area of Codonopsis Radix was compared, involved in the similarities and differences of the number and the relative peak area of characteristic peaks in the HPLC specific chromatograms. The HPLC specific chromatograms of Lu Dangshen was established and the relative retention times of seven peaks was determined, and the peaks of codonopyrrolidium B, syringin, lobetyolin, tangshenoside I and atractylenoide III were identified; The HPLC specific chromatograms of Lu Dangshen provided a method for scientific evaluation and effective control the quality of Lu Dangshen from Shanxi famous-region.
Chromatography, High Pressure Liquid ; methods ; Codonopsis ; chemistry ; Drugs, Chinese Herbal ; analysis ; Glucosides ; analysis ; Phenylpropionates ; analysis ; Plant Roots ; chemistry ; Quality Control

The 11-hydroxylation of 16alpha,17alpha-epoxy-4-pregenene-3,20-dione as a useful intermediate for the preparation of hormones can be achieved by the mycelium of Absidia coerulea at higher conversion rate than using other strains. In this paper 16alpha,17alpha-epoxy-4-pregenene-3,20-dione mixed with a little water, beta-cyclodextrin, Tween-80 was introduced into the fermentation broth after ultrasonication to increase pseudo-water-solubility of the hydrophobic substrate. This pseudo-crystallo feed could avoid the toxicity of organic solvents and was more available for the microbial transformation. The multi layer feed-forward neural network was used to setup a model which indicated the relationship between medium and feed components and the conversion rate. Particle swarm optimization (PSO), which was a stochastic global optimization algorithm and of which the convergence speed was high, was applied to obtain the optimal concentration of the medium and feed components. At optimum conditions with the pseudo-crystallo feed, the conversion rate of 16alpha,17alpha-epoxy-4-pregenene-3,20-dione at an initial concentration of 10 g/L was 87.5% in shaking flasks. The conversion rate of the substrate was up to 86.6% at higher concentration of 20 g/L feed in a 3.7 L fermentor.
Absidia ; metabolism ; Fermentation ; Hydroxylation ; Pregnenediones ; metabolism

OBJECTIVETo establish a three-dimension finite element model of mandible with two kinds of dental implant and to study the stress of implant-bone interface.

METHODSMeasuring the data of the components of the dental implant and using spiral CT image reconstruction technique to scan the cross section of the mandible. Three-dimension finite element analysis software Unigraphics and MSC. Marc/Mentat were used to build the conjunction model and bone model of two implant systems. Loading 200 N axially and 100 N 30 degrees obliquely on the models respectively, the stress distribution patterns of the bone interface of two implant systems were analyzed.

RESULTSThe stress distribution on the bone interface of two implant systems was similar. The peak stress of oblique loading was higher than that of axial loading. The peak stress district of the bone was concentrated on the stricture of the implant cervix, which was more obviously displayed on the Replace Select implant. The peak stresses on the bone interface of Replace Select implant were higher than that of Replace implant in all loadings.

CONCLUSIONTo Replace Select especially, oblique force should be avoided in clinical practice in case of the bone absorption.

Computer Simulation ; Dental Implants ; Finite Element Analysis ; Humans ; Mandible ; Stress, Mechanical

BACKGROUNDBlocking the 4-1BB/4-1BB ligand (4-1BBL) signal may modulate the secretion of Th1/Th2 cytokines and prolong the survival of the grafts, which play a key role in organ transplantation tolerance. The aim of this study was to investigate the role of blockade of the 4-1BB/4-1BBL co-stimulatory pathway with 4-1BBL monoclonal antibody (mAB) in acute rejection of rat orthotopic liver transplantation.

METHODSThe orthotopic liver transplantation model was set up, while male Lewis rats were used as liver donors and Brown-Norway rats as recipients. The recipient rats were intravenously injected with anti 4-1BBL mAB or isotype control antibody. Groups were monitored for graft survival after transplantation. Plasma chemistry, including aspartate transaminase (AST), alanine aminotransferase (ALT), and bilirubin (BIL), was assayed. The concentrations of interleukin (IL)-2, IL-10 and interferon (IFN)-gamma in plasma were also measured by enzyme-linked immunosorbent assay. Allograft histology images were collected under light microscope and electron microscope.

RESULTSIsotype antibody treated recipients exhibited elevated plasma levels of liver injury markers including AST, ALT and BIL, progressive portal and venous inflammation and cellular infiltration of the liver allografts, and a mean graft survival time (MST) of 10.9 days. Administration of anti 4-1BBL mAB resulted in a decrease in plasma levels of liver injury markers and the concentrations of IL-2, IL-10 and IFN-gamma. The histological grade of rejection on day 7 decreased and MST (17.3 days) increased substantially.

CONCLUSIONSThese results demonstrate that attenuation of acute rejection follows the blockade of the 4-1BB/4-1BBL co-stimulatory pathway with 4-1BBL monoclonal antibody and strongly suggest it is a promising strategy to prevent progression of graft rejection by suppressing T cell-mediated immunity.

4-1BB Ligand ; immunology ; Alanine Transaminase ; metabolism ; Animals ; Antibodies, Monoclonal ; pharmacology ; therapeutic use ; Aspartate Aminotransferases ; metabolism ; Bilirubin ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Graft Rejection ; immunology ; prevention & control ; Graft Survival ; drug effects ; Interferon-gamma ; blood ; Interleukin-10 ; blood ; Interleukin-2 ; blood ; Liver Transplantation ; adverse effects ; Male ; Rats ; Rats, Inbred Lew

OBJECTIVETo investigate the effect of a sequence-specific small interfering RNA (siRNA) in suppressing survivin expression and cell proliferation and inducing apoptosis of PC-2 cells.

METHODSThe plasmid expression vector of siRNA targeted against survivin was constructed and transfected into PC-2 cells with Lipofectamine 2000. The changes of survivin expression were detected by semi-quantitative RT-PCR and immunohistochemical SP methods. The effect of siRNA in suppressing the proliferation of PC-2 cells was detected by MTT assay, and its role in inducing PC-2 cell apoptosis evaluated by flow cytometry.

RESULTSThe sequence-specific siRNA effectively suppressed survivin expression at both mRNA and protein levels with inhibition rate of 81.25% at mRNA level and 74.24% at protein level. Survivin expression suppression significantly inhibited the proliferation of PC-2 cells, and at 24 and 48 h after cell seeding, the proliferation inhibition rate was 28.00% and 33.38% respectively; 24, 48 h after the transfection, apoptosis occurred in 8.46% and 7.53% of the cells, respectively.

CONCLUSIONSThe plasmid expression vector for the siRNA against survivin constructed in the study can effectively and specifically suppress survivin expression in PC-2 cells, and blocking survivin expression suppresses PC-2 cell proliferation and induces cell apoptosis. siRNA targeted against survivin has a potential value in gene therapy for pancreatic cancer.

Apoptosis ; genetics ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; genetics ; Humans ; Inhibitor of Apoptosis Proteins ; Microtubule-Associated Proteins ; biosynthesis ; genetics ; Neoplasm Proteins ; biosynthesis ; genetics ; Pancreatic Neoplasms ; genetics ; pathology ; RNA Interference ; RNA, Messenger ; biosynthesis ; genetics ; RNA, Small Interfering ; genetics ; Transfection

BACKGROUNDThe antitumor role of Ras association domain family 1A (RASSF1A) gene and its potential molecular mechanisms are not well understood. The objective of this study was to observe the antitumor ability of RASSF1A in hepatocellular carcinoma, and study the mechanisms of cell apoptosis induced by RASSF1A.

METHODSAfter stably transfecting a RASSF1A (wild-type or mutant) expression vector into the BEL-7402 hepatocellular carcinoma cell line, RT-PCR and Western blotting was used to detect the RASSF1A expression levels in recombinant cells. The effects of wild-type RASSF1A on cell growth were observed in vitro by analyzing cell proliferation rate, cell colony formation, and in vivo by analyzing tumorigenesis in nude mice. In addition, the effect of RASSF1A gene expression on the chemosensitivity of human hepatocellular carcinoma cells to antitumor drugs was examined by inhibition of cell proliferation and the percentage of apoptotic cells.

RESULTSWild-type RASSF1A, not the mutant, suppressed cell growth in vitro and in vivo. Re-expression of wild-type RASSF1A could enhance the inhibition of cell proliferation and the percentage of apoptotic cells following cell treatment with mitomycin, but had no significant effect when combined with adriamycin, etoposide, 5-fluorouracil and cisplatin treatment.

CONCLUSIONWild-type RASSF1A inhibits cell growth and enhances cell chemosensitivity to mitomycin in hepatocellular carcinoma, suggesting that RASSF1A may serve as a new target for gene therapy in hepatocellular carcinoma patients.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; genetics ; Blotting, Western ; Carcinoma, Hepatocellular ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Genetic Therapy ; methods ; Humans ; Mitomycin ; pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Suppressor Proteins ; genetics ; metabolism ; physiology

OBJECTIVETo explore the relationship of plasminogen activator inhibitor-1 (PAI-1) gene-675 4G/5G and methylenetetrahydrofolate reductase(MTHFR) gene C677T polymorphisms to recurrent early spontaneous abortion(RESA).

METHODSOne hundred and twenty-seven currently non-pregnant women with at least 3 unexplained spontaneous abortions during the first trimester of pregnancy (patient group). Normal control group consisted of 117 currently non-pregnant women with at least 1 pregnancy and without a history of prematurity, miscarriage, stillbirth, eclampsia and other pregnancy complications. The genotypes of PAI-1 gene and MTHFR gene were assessed by polymerase chain reaction-restrictive fragment length polymorphism.

RESULTSThe frequencies of 4G/4G genotype and 4G allele of PAI-1 were higher in patient group (45.7% and 66.1%) than in normal controls (17.1% and 46.6%) (P < 0.01). The PAI-1 4G/4G genotype was significantly associated with RESA (OR = 4.8, 95% CI: 2.23 - 10.35). Besides, MTHFR gene T/T genotype and T allele frequencies were increased in RESA patients (43.3% and 66.5%) versus normal controls (21.4% and 52.6%) (P < 0.01). The patients carrying T/T genotype had a high risk of early spontaneous abortion (OR = 3.2, 95% CI: 1.40 - 7.30). In additionìthe presence of the PAI-1 gene 4G/4G genotype together with the T/T genotype of the MTHFR gene was found to be a risk factor (OR = 6.20, 95% CI: 2.62 - 14.67) for RESA greater than the 4G/4G genotype or the T/T genotype alone.

CONCLUSIONThe above findings suggest that genetic polymorphisms of PAI-1 4G/5G and MTHFR C677T were associated with RESA. They may have synergetic impact and present gene dosage effect on the susceptibility to the development of early spontaneous abortion.

Abortion, Habitual ; genetics ; Adult ; Alleles ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Plasminogen Activator Inhibitor 1 ; genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; Polymorphism, Restriction Fragment Length ; Pregnancy ; Young Adult

OBJECTIVETo investigate the effect of the gene nanoparticles using chitosan (CNP), arginine modified chitosan (ANP), or hexadecylated chitosan (HNP) as carriers on the human normal liver cell line L02.

METHODSCNPs, ANPs, and HNPs were prepared using complex coacervation method. The size and zeta potential of the gene nanoparticles were measured using Zetasizer nanoZS. The nanoparticles at concentrations of 5, 10, 30, and 50 microg/ml (based on the content of DNA) were incubated with L02 cells, respectively. The cell viability was evaluated by MTT assay, and the effect of the gene nanoparticles on the cell apoptosis was analyzed by flow cytometry.

RESULTSThe zeta potential of the gene nanoparticles ranged from 12.10 to 14.63 mV, and their diameters ranged from 148.07 to 179.47 nm. MTT assay showed that the viability of L02 cells began to decrease when the concentration of CNPs reached 30 microg/ml and higher. Furthermore, the CNPs could induce cell apoptosis as the concentration of CNPs reached 30 microg/ml and higher.

CONCLUSIONCNPs can induce L02 cell apoptosis at relatively higher concentrations.

Apoptosis ; Cell Line ; Cell Survival ; Chitosan ; chemistry ; DNA ; chemistry ; genetics ; Gene Transfer Techniques ; instrumentation ; Humans ; Nanoparticles ; chemistry

OBJECTIVETo fabricate polyvinyl alcohol (PVA)/chitosan hybrid nanofibrous scaffolds owning the similar physiological structure of ECM, and to observe its biodegradation behavior in vivo and in vitro.

METHODS(1) The PVA nanofibrous scaffold and PVA/chitosan hybrid nanofibrous scaffold were fabricated by electrospinning technique, and then they were crosslinked by glutaraldehyde vapor method. The morphology of both scaffolds was observed by scanning electron microscope (SEM). (2) Biodegradation experiment in vitro: the samples of two scaffolds with size of 2 cm x 2 cm were placed into phosphate-buffer saline (PBS) fluid under 37.0 degrees C water for incubation, and then they were dried to observe morphologic changes under SEM on post incubation day (PID) 3, 7, and 14. (3) Biodegradation experiment in vivo: 48 Wistar rats were divided into PVA group and PVA/chitosan group according to the random number table, with 24 rats in each group. PVA or PVA/chitosan nanofibrous scaffold was implanted into subcutaneous tissue on both sides of back in rats of both groups, with 4 scaffolds in each rat. The scaffold samples were harvested to observe morphologic changes with HE staining on post operation day (POD) 3, 7, 14, and 28.

RESULTS(1) After crosslinking, the surface of fibers in PVA and PVA/chitosan hybrid nanofibrous scaffolds were smooth, and the diameters of fibers were similar, ranging from 200 to 300 nm, with high porosity. (2) Biodegradation experiment in vitro showed that the morphologic changes in fiber was respectively swelling, dissolution, fusion in PVA nanofibrous scaffold on PID 3, 7, 14, and that in PVA/chitosan hybrid nanofibrous scaffold was respectively swelling, dissolution and fragmentation, and disappearance. (3) Biodegradation experiment in vivo showed that the morphologic changes in scaffold structure was respectively loosening, fuzziness of edges, degradation, and disappearance in PVA group and PVA/chitosan group on POD 3, 7, 14, 28.

CONCLUSIONSPVA/chitosan hybrid nanofibrous scaffolds can be prepared with electrospinning technique, and it has an appropriate biodegradation rate compatible with tissue reconstruction after crosslinking.

Animals ; Biocompatible Materials ; Cells, Cultured ; Chitosan ; chemical synthesis ; chemistry ; Materials Testing ; Polyvinyl Alcohol ; chemical synthesis ; chemistry ; Rats ; Rats, Wistar ; Tissue Engineering ; methods ; Tissue Scaffolds