OBJECTIVE:To provide reference for improving the drug price regulation policy in China. METHODS:Literature research,system comparison and other methods were used to summarize the commonalities and characteristics of drug price regula-tion policy in Germany,Japan and Taiwan area of China,and the successful experience was learned. RESULTS & CONCLU-SIONS:Drug price management in Germany,Japan and Taiwan area of China has their own characteristics. Germany conducted reference price system and new drug pricing mechanism,which was the first country to introduce the reference price system. Japan granted price premiums to innovative drugs,decreased pricing for generic drugs and adjusted drug price again. And Taiwan area of China classified and grouped differential pricing to encourage competition negotiation and regularly investigated drug prices and pric-ing. Germany,Japan and Taiwan area regard medicare pay price as core of drug price management,adopt comprehensive means to regulate the drug price,and pay attention to the monitoring and regular adjustment of market price as well. Price negotiation,phar-macoeconomics and multiple pricing methods are broadly used. Value-based drug pricing system is new trend of price policy re-form. It can be used for reference to improve the drug price regulation system in China.

Brain ; Humans ; Neoplasms ; Neurogenesis

Objective To investigate the role and mechanism of RSPO1 in osteoblasts differentiation.Methods The xCELLigence system was used to study the toxicity and role of RSPO1 on the C2C12 cells proliferation.Alkaline phosphatase (ALP) activity was measured by using a phosphatase detection kit.The expression of osteoprotegerin (OPG) was determined using enzyme-linked immunosorbent assay (ELISA).Wnt/β-catenin signaling was evaluated using the TOPflash T cell factor (TCF) luciferase reporter assay.Western blotting assay was performed to confirm the accumulation of β-catenin protein.T test was used for statistical analysis.Results RSPO1 had no effect on the C2C12 cells proliferation,and it produced no toxicity to C2C12 cells.RSPO1 alone resulted in a slight increase in the activity of ALP (2.85±0.08 vs 1.74±0.21,t=3.014,P＜0.05) and the expression of OPG (1.29±0.13 vs 1.00±0.21,t=3.348,P＜0.05),whereas the combination of RSPO1 and Wnt3A significantly amplified ALP activity (81.37±5.08 vs 1.74±0.21,t=31.31,P＜0.01) and OPG protein expression (5.26±0.60 vs 1.00±0.21,t=6.99,P＜0.01).RSPO1 synergized with Wnt3A to activate TCF activity and induce accumulation of β-catenin (3.28±0.18 vs 1.00±0.21,t=10.94,P＜0.05).However,RSPO1 alone had no effect on the TCF activity and β-catenin accumulation (1.25±0.08 vs 1.00±0.21,t=2.225,P＞0.05).Conclusion Our study has revealed that RSPO1 synergized with Wnt3A in activating Wnt/β-catenin signaling pathway to induce osteoblasts differentiation,which demonstrate the therapeutic potential of RSPO1 for RA.

OBJECTIVE:To provide reference for dynamic adjustment of low-cost medicine lists and better guarantee of low-cost supply in those provinces,autonomous regions and municipalities[referred to provinces(autonomous regions or municipali-ties)]. METHODS:The varieties and frequency of medicines in the national and 31 province(autonomous regions or municipali-ties) lists were counted,and the influential factors were analyzed. RESULTS:The National Low-cost Medicine List included 533 varieties of medicines,including 283 western medicines,250 Chinese patent medicines and 60 exclusive varieties. There were total-ly 973 varieties of medicines in the 31 province(autonomous regions or municipalities),including 332 western medicines,630 Chi-nese patent medicines,11 ethnic medicines and 71 protected Chinese medicines. There was no big difference in the varieties be-tween the eastern and western areas,and less in the central areas. Guangxi province had the largest number of selected medicines (345 varieties) and Jiangxi province had the smallest (10 varieties). In all the varieties,Chinese medicines had a larger number than western medicines,and also better concentration. Ketotifen was the most frequent western medicine and Tongbianling capsule was the most frequent Chinese patent medicine,which appeared 30 and 29 times separately. The Provincial Low-cost Medicine Lists and the Essential Medicine Supplement Lists had a poor coincidence rate,and there was a moderate correlation between the varieties and the number of pharmaceutical manufacturers in the province(autonomous regions or municipalities). CONCLUSIONS:The adjustment of low-cost medicine lists should be combined with these in province(autonomous regions or municipalities) near-by,and notice the linkage with national essential medicine system to fundamentally ensure the clinical medication requirements of patients.

Objective To investigate the effect of VPA and molecular hydrogen(H2)on phenotypes of microglia treated with hypoxia. Methods Mouse hypoxic BV2 microglia were treated with VPA or H2. The levels of phenotypic markers of supernatant and cells were detected by ELISA, flow cytometry and real?time PCR,respectively. Results Hypoxia significantly increased mRNA level of M1 marker(iNOS)and reduced mRNA levels of M2 markers(CD206 and TGF?β)in BV2(P<0.05). Besides,the ratio between the mRNA levels of M1 increased(P<0.05). VPA significantly reduced protein level(CD16/32)and mRNA production(iNOS)of M1 markers in hypoxia?treated BV2(P<0.05). The ratio be?tween the mRNA levels of M1 markers and M2 markers(CD16:CD206,CD32:CD206,iNOS:CD206 and iNOS:TGF?β)were also significantly decreased(P<0.05). H2 significantly reduced both protein levels(TNF?α,CD16/32 and iNOS)and mRNA production(iNOS)of M1 markers and increased secretion of M2 marker(IL?10)in hypoxia?treated BV2(P<0.05). The ratio between the mRNA levels of M1 markers and M2 markers(CD16:CD206,iNOS:CD206 and iNOS:TGF?β)were also highly declined(P<0.05). Conclusion Hypoxia can induce microglial cells toward pro?inflammatory phenotype. Both VPA and H2 can inhibit hypoxia?induced inflammatory effect on microglia.

Objective To develop a predictive model for pulmonary embolism(PE)based on the related clinical symptoms,signs,and the labo-ratory index,so as to improve the positive rate of CTPA. Methods The model was developed from a database of 119 patients with suspected PE. The risk factors of suspected PE were analyzed by logistic regression analysis ,which included significant differences in the prevalence of PE be-tween non-diseased and non-diseased groups. Receiver operating characteristic(ROC)curves was draw to determine the cut-off value of the clini-cal probability. It was validated in an independent sample of 106 patients with suspected PE. Results According to the univariate analysis ,17 of 51 variables show a significant difference between PE and non-PE patients. The model comprised 4 variables:age,dyspnea,D-dimer and unilater-al leg swelling. The area under the ROC curve is 0.776,and the cut-off value is supposed to be 0.38. In the validation sample,27% patients had PE confirmed by CTPA. The prevalence of PE was 54%when the clinical probability was above 0.38. Conclusion The proposed predictive mod-el in this study can improve the positive rate of CTPA ,simplify the diagnosis process of suspected PE patients.

Objective To analyze the effects of valproic acid(VPA),a histone deacetylase(HDAC)inhibitor,on macrophage polarization in?duced by paraquat(PQ)or lipopolysaccharide(LPS). Methods Mouse RAW264.7 cells were cultured at 37℃with 5%CO2,passaged,and then given one of the following treatments:(1)PQ;(2)PQ+VPA(classⅠandⅡa HDAC inhibitor);(3)PQ+apicidin(classⅠHDAC inhibitor);(4)PQ+MC1568(classⅡa HDAC inhibitor);(5)LPS;(6)LPS+VPA;(7)LPS+apicidin;(8)LPS+MC1568. The cells and culture supernatants were harvested after 8 h of treatment. RT?PCR,ELISA,and flow cytometry were conducted to assess the expression levels of macrophage phenotyp?ic markers. Results Both PQ and LPS skewed the macrophage functional polarity toward proinflammatory phenotype. VPA,apicidin,and MC1568 all inhibited PQ?and LPS?induced macrophages polarizing toward pro?inflammatory phenotype ,but the inhibitory effects were different in some ways. Conclusion VPA inhibits the proinflammatory function of macrophages induced by PQ and LPS ,but the effect of VPA on PQ?and LPS?induced macrophages has its own characteristics.

Objective:This study aims to analyze of the quality of diagnosis and treatment data of community medical institutions on the national health information platform in a district of Beijing from the perspective of scientific research informatization, to provide experience and reference for promoting the informatization construction of primary medical units and tapping the scientific research potential of the regional data platform.Methods:Based on the data backup database of the national health information platform in the region, the data quality was analyzed and evaluated mainly in three dimensions: integrity, integration, and consistency.Results:Through the construction of the national health information platform, the district successfully achieved the effective collection of diagnosis and treatment data from community medical institutions, covering the main data such as patients′ basic information, visit information, test information, prescription information, etc. However, the data collected so far were still insufficient in terms of data integration and consistency.Conclusions:A regional medical data center is suggested to construct to break down the barriers between data systems, conduct pre-structuring of diagnosis and treatment data, improve data integration and consistency, and at the same time, carry out effective scientific research prospective design to promote the effective transformation of clinical data to scientific research data.

Objective To investigate whether cannabinoid receptor 1 (CB1R) is involved in nerve growth in endometriosis-associated ectopic cyst.Methods The effect of CB1R agonist and antagonist on the expression of pan-neuronal marker protein gene product ( PGP ) 9.5 in ectopic cyst was examined by immunofluorescence and Western blot in endometriosis model of 18 rats.Results Immunofluorescence revealed that PGP 9.5 was expressed in the nerve fibers and was mainly distributed in the cyst hilum. Western blot revealed that the protein density of either PGP 9.5 (2 week:0.38 ±0.05;4 week:0.63 ± 0.03;8 week:0.80 ±0.07, P<0.01) or CB1R(2 week:0.48 ±0.04;4 week:0.68 ±0.01;8 week:0.80 ±0.03, P<0.01) in the ectopic cyst increased with cyst size.In addition, compared to control group (0.75 ±0.01), PGP 9.5 expression in the ectopic cyst was promoted by CB1R agonist ACPA (0.81 ± 0.01, P <0.05), and inhibited by CB1R antagonist AM251 (0.67 ±0.03, P <0.01) .Conclusions CB1R was involved in the nerve growth of ectopic cyst associated with endometriosis.

Objective To detect the expression of pan-neuronal marker protein gene product ( PGP)9.5 and its clinicopathologic significance in breast cancer .Methods The expression of PGP9.5 was examined by immunohistochemistry EnVision method in 196 cases during 2007 to 2011, including 20 normal tissues, 14 cases of fibroadenoma , 18 cases of ductal carcinoma in situ ( DCIS) and 144 cases of invasive ductal carcinoma (IDC) of the breast.The relationship between PGP9.5 expression and clinicopathologic characteristics of IDC was assessed.Results PGP9.5 expression was localized in the stroma of all normal breast tissues, but there was no expression observed in all fibroadenomas and DCIS.Overall, the expression rate of PGP9.5 in IDC was 61.8%(89/144).PGP9.5 expression increased from grade 1 tumors (29.4%, 10/34) to grade 2-3 tumors (71.8%, 79/110; P=0.000).In addition, patients with less than 3 years disease-free survival tended to show higher PGP9.5 expression (64.8%, 35/54), compared to patients with equal to and/or more than 3 years disease-free survival (46.7%, 42/90;P=0.035).However, there was no correlation between PGP 9.5 expression and tumor size , tumor stage , lymph metastasis , hormone receptor expression.Conclusion PGP9.5 expression is correlated with tumor grade and prognosis in IDC of the breast.