Germany has a similar health insurance system as China, and has already formed standardized management processes as well as efficient decision-making transformation paths for health technology assessment (HTA) that perform well mainly based on three major HTA institutions at the national level.The HTA decision-making transformation system in Germany has proven to be a typical representative in evidence-based decision-making for health policies worldwide.Based on the outcomes of literature analysis and field research, this paper summarizes the paths and methods of Germany's HTA decision-making transformation, and finally proposes several targeted policy recommendations to promote the HTA decision-making transformation in China.

OBJECTIVE To investigate the pattern of fungal isolates from hospital-acquired infection in tumor patients after chemotherapy. METHODS The clinical information of fungus isolates from 102 tumor patients after chemotherapy was investigated.We analyzed the risk factors,species and drug-resistance of isolates. RESULTS The lower respiratory tract and mouth infection accounted for 61.8% and 16.7% in 102 cases with fungal infection and 102 isolates were isolated from various clinical specimens.Among above 102 isolates,Candida albicans and C.tropicalis accounted for 71.6% and 14.7%.The resistant rate of C.albicans to fluconazole and miconazole were 96.2% and 61.4%,respectively. CONCLUSIONS Hospital-acquired infection resulted from fungi in tumor patients after chemotherapy is related to primary tumor,age,the amount of white cell and use of antibiotics.

AIM: To investigate the effect of yigu capsule drug-containing serum on proliferation, ALP activity and expression of interleukin-11 mRNA in Sprague-Dawley rat osteobalsts in the co-culture system. METHODS: (1) Osteoblasts and osteoclasts were isolated from 1 and 5-day-old Sprague-Dawley rats, respectively. The osteoblasts-osteoclasts co-culture system was built to prevent the two kinds of cells from contact and allow the media to exchange. The experiment included two groups, drug-containing sera group and control group. (2) The osteoblasts proliferation, ALP activity and expression of interleukin-11 mRNA were detected by the MTT, 4-aminoantipyrine spectrometric methods and FQ-PCR,respectively. RESULTS: In drug-containing sera group, the osteoblasts proliferation, ALP activity, expression of IL-11 mRNA were higher than those of control group (P

AIM:To observe the effect of TNF-? and Yigu capsule drug-containing sera on osteoblasts apoptosis in osteoblasts-osteoclasts coculture system.METHODS:(1)Twenty female Sprague-Dawley rats,10 months old,were randomly assigned into 2 groups,NS and Yigu capsule groups,to prepare blank sera and drug-containing sera.(2)The DNA gel electrophoresis method was used to detect apoptosis of osteoblasts treated with different concentration of TNF-? in order to determine the best dosage in the co-culture system.(3)The cells were divided into four groups,TNF-? group,normal group,TNF-? + blank serum group and TNF-? + drug-containing serum group.DNA gel electrophoresis,acridine orange staining and flow cytometry were used to observe osteoblast apoptosis in these groups.RESULTS:(1)After induced by TNF-? for 72 h at a concentration of 60 ?g/L,relatively typical DNA ladder appeared in TNF-? group.(2)Only two DNA brands appeared and most of cells were well-proportioned stained in TNF-? + drug-containing serum group,the rate of osteoblasts apoptosis in TNF-? + drug-containing serum group(9.60%?0.26%)was obviously lower than that in the TNF-? group(26.90%?0.06%)and TNF-? + blank serum group(18.10%?0.06%).CONCLUSION:TNF-? induces osteoblast apoptosis in the co-culture system,and Yigu capsule drug-containing serum prevents osteoblast apoptosis induced by TNF-?.

AIM: To study the effect of Bone-benefiting capsule(BBC)-containing serum on activity and apoptosis of osteoclasts(OC) in osteoblasts(OB) and osteoclasts co-culture system.METHODS:(1) OB were separated from the skull of SD rats aged 1 d and OC from the thighbone and shinbone of SD rats aged 5 d,the plane OB and OC co-culture system was established,in which the cells in each culture system did not intermix,but the culture medium communicated,and BBC-containing serum group and control group were concluded in the experiment.(2) Female SD rats aged 10 months were divided into BBC group and control group to prepare BBC-containing serum and control serum.(3) The TRAP secreted by OC was measured by the diazol method and the absorption of lacuna formed by OC was observed by microscope in OB and OC co-culture system to determine the activity of OC with the effect of BBC-containing serum.(4) The effect of BBC-containing serum on OC apoptosis in OB and OC co-culture system was examined by optical microscopes and fluorescence microscopes.RESULTS: In OB and OC co-culture system,the activity of TRAP secreted by OC of BBC-containing serum group were obviously lower than that of control group in 48 h,72 h and 96 h,the OC surviving numbers were obviously lower than that of control group and the rate of OC apoptosis was markedly higher than that of control group which showed an obvious time-efficiency relationship;the amount of the absorption of lacuna formed by OC in BBC-containing serum group was evidently lower than that of control group(P

AIM:To investigate the changes of Wnt signaling pathway in catalpol-induced proliferation of rat bone marrow mesenchymal stem cells (BMSCs).METHODS:The BMSCs were isolated from SD rats , purified by differ-ential time adherent method and divided into control group and catalpol (1.0 mg/L) group.Flow cytometry was used to de-tect the proliferation index of BMSCs .The mRNA levels of Wnt3a, Wnt5a, Wnt11 and β-catenin was evaluated by real-time PCR.In addition, the protein expression level of β-catenin was determined by Western blotting .RESULTS:Prolife-ration index was increased from 8.90%±0.46% to 17.93%±1.68% after treatment with catalpol (P<0.01).Com-pared with control group , the mRNA expression of Wnt5a, Wnt11 andβ-catenin was all increased with catalpol treatment . No difference of Wnt3a mRNA expression between control group and catalpol group was observed .Meanwhile, the protein expression of β-catenin was increased in catalpol group compared with control group .CONCLUSION:Catalpol promotes BMSCs going into the cell cycle .Classical and non-classical Wnt signaling pathways are activated in this process .

OBJECTIVE:To study the effects of exogenous abscisic acid(ABA)on salt-alkali tolerance of Scrophularia ning-poensis seedlings,and to provide theoretic evidence for cultivating S. ningpoensis in salt-alkali soil. METHODS:50 S. ningpoensis seedlings were divided into control group,salt-alkali group(75 mmol/L),salt-alkali(75 mmol/L)+ABA low-concentration,medi-um-concentration and high-concentration groups(10,50,100 μmol/L),with 10 plants in each group. 20 days after transplanting, the plants were sprayed with drugs every 4 days. Growth indexes of the plants(length of stem,fresh weight,dry weight,survival rate),physiological indexes [the contents of chlorophyll,soluble sugar (SS),soluble protein (SP) and free proline (Pro)],the contents of MDA and H2O2,the activities of antioxidase [the activities of SOD,POD,CAT,GR] and the contents of Na+ and K+in stem and root were determined in each group 2 weeks later. RESULTS:Compared with control group,stem height and survival rate of S. ningpoensis seedlings,SP,the contents of Na+ and K+ in the stem,the contents of Na+,CAT and GR in the roots were all decreased significantly in salt-alkali group;while chlorophyll,Pro,MDA and H2O2 contents,the content of K+ in the roots and the activities of SOD and POD were all increased significantly(P<0.05 or P<0.01). Compared with salt-alkali group,stem height of S. ningpoensis seedlings,fresh weight and chlorophyll content were increased significantly in salt-alkali+ABA medium-concentra-tion group,while MDA and the content of Na+ in the stem were decreased significantly;dry weight,the contents of SS and SP, the activities of SOD and CAT were increased significantly in salt-alkali+ABA low-concentration and medium-concentration groups, while the SS content was increased in salt-alkali+ABA high-concentration group;stem height and dry weight were decreased signifi-cantly in salt-alkali+ABA high-concentration group;Pro content of salt-alkali+ABA low-concentration and high-concentration groups were decreased significantly;H2O2,Na+ content in the roots were decreased significantly in salt-alkali+ABA low-concentra-tion,medium-concentration and high-concentration groups;while GR activity,K+ content in the stem and roots were increased sig-nificantly;POD activity were decreased significantly in salt-alkali+ABA medium-concentration and high-concentration groups. CON-CLUSIONS:The addition of a certain concentration of exogenous ABA can effectively increase salt-alkali tolerance of S. ningpoen-sis seedlings and strengthen the ability of the plant adapting to salt-alkali environment.

Objective To screen the non-nucleoside compounds against HIV-1 reverse transcriptase by molecular modeling and bioactivity assay. Methods Surflex-Dock module of Tripos SYBYL software was used to simulate the binding pattern of 22 000 compounds in SPECS database with the active pocket of HIV-1 reverse transcriptase. Based on the simulation results, the interaction mode between the above compounds and the crystal structure of HIV-1 reverse transcriptase was analyzed. The compounds with higher docking scores and better binding pattern were determined by anti-HIV-1 ac tivities test in vitro. Results The virtual screening results showed that the docking conformation of 1- (4-fluorophenyl) -3- [2- (1H-indol-3-yl) ethyl] thiourea was similar to the embedded ligand in Rilpivirine crystal structure. 1- ( 4-fluorophenyl) -3- [ 2- ( 1H-indol-3-yl) ethyl] thiourea was held together with the key residue Lys101 in docking pocket of HIV-1 reverse transcriptase by hydrogen bonds, and hadπ-πstacking action together with the conservative residue Trp229 and the aromatic residue Tyr181 respectively. The bioassay in vitro results showed that when the proliferation rate of C8166 lymphocyte syncytium infected by HIV-1ⅢB arrived 50% ( EC50) , the concentration of 1- ( 4-fluorophenyl) -3- [ 2- ( 1H-indol-3-yl) ethyl] thiourea was 5.45μg/mL. Conclusion Molecule docking technology is an effective approach to reducing the screening of candidate compounds with micromolecular activity, and can be used to predict the interaction mode between the compound and the target receptor. In the study, active compound 1- (4-fluorophenyl) -3- [2- (1H-indol-3-yl) ethyl] thiourea has been screened out by molecule docking technology.

Objective:To investigate expression profiles of the plasma exosomal miRNAs of the chronic hepatitis B (CHB) patients with persistently normal alamine aminotransferase (PNALT) for the first time and try to find exosomal miRNAs which could reflect liver inflammation better.Methods:Five CHB patients with liver tissue inflammation grade ≥A2 of PNALT and 5 CHB patients with liver tissue inflammation grade ＜A2 of PNALT were enrolled and their blood samples were collected.The exosomes were extracted from these blood samples and measured by electron microscope to determine the extraction effect.The exosomal miRNAs were extracted and sent for high throughput sequencing,and the expression of exosomal miRNAs in the 2 groups of patients was analyzed.Results:Under the electron microscope,exosomes were small membranous vesicles with 30-100 nm in diameter.The peak value of particle size ranged from 10 to 100 nm.High throughput sequencing showed that there were 591 differentially expressed exosomal miRNAs between the 2 groups.Compared with the control group,18 exosomal miRNAs were up-regulated and 6 exosomal miRNAs were down-regulated in PNALT patients with the liver tissue inflammation grade ≥ A2.Conclusion:Exosomal miRNAs in the CHB patients with PNALT who have the different grades of liver inflammation are differently expressed.Some of the differently expressed exosomal miRNAs are expected to be sensitive biomarkers for timely assessment of liver inflammation in the CHB patients with PNALT.

OBJECTIVETo evaluate the effect of mycophenolate mofetile (MMF) on acute graft versus host disease (aGVHD) prophylaxis after allogeneic bone marrow transplantation (allo-BMT) in a murine model.

METHODSAcute GVHD was induced in male BALB/c mice by total-body irradiation (TBI) followed by female allogeneic (C57BL/6J) bone marrow and spleen cells transplantation. Acute GVHD was assessed both physically and histologically. Severe aGVHD was developed in the recipients and the mean survival time (MST) of untreated BM recipients was 6 days. After allo-BMT, animals were divided into 6 groups. Group 1 was given MMF (30 mg.kg(-1).d(-1)), group 2 CsA (1.5 mg.kg(-1).d(-1)) and MTX (0.4 mg.kg(-1).d(-1)), group 3 MMF (30 mg.kg(-1).d(-1)) in combination with CsA and MTX, group 4 MMF (60 mg.kg(-1).d(-1)) in combination with CsA and MTX, group 5 MMF (10 mg.kg(-1).d(-1)) in combination with CsA and MTX, and group 6 no agents for aGVHD prophylaxis. The physical signs, MST, peripheral blood counts, and aGVHD histopathologic examination were observed in all recipients.

RESULTSAnimals in control group developed typical aGVHD and 100% of mortality, with a MST of 6 days. The MSTs of group 1 approximately 5 were significantly longer than that of control, being 3.4, 8.4, 9.0, 6.1 and 8.8 days longer, respectively (P < 0.05). The MSTs of groups 2 approximately 5 were longer than that of group 1 (P < 0.05), but there was no statistical significance between groups 3 approximately 5 and 2. There was no statistical difference in peripheral blood count among groups 1 approximately 5. Histopathological examination of skin, liver, and gastrointestinal tract showed typical signs of aGVHD. Animals received immunosuppressive agents (MMF, CsA, MTX) showed the less severe signs.

CONCLUSIONSMMF markedly prolonged MST of allo-BMT recipients, delayed the onset of aGVHD signs. The prophylaxis effect of CsA + MTX with or without MMF was better than that of MMF alone, synergism between MMF of 10 or 30 mg.kg(-1).d(-1) and CsA + MTX was better than that of MMF of 60 mg.kg(-1).d(-1) and CsA + MTX.

Animals ; Bone Marrow Transplantation ; Cyclosporine ; pharmacology ; Dose-Response Relationship, Drug ; Drug Synergism ; Female ; Graft Survival ; drug effects ; Graft vs Host Disease ; pathology ; prevention & control ; Immunosuppressive Agents ; pharmacology ; Methotrexate ; pharmacology ; Mice ; Mice, Inbred C57BL ; Models, Animal ; Mycophenolic Acid ; analogs & derivatives ; pharmacology ; Time Factors ; Transplantation, Homologous