AIM:To introduce the concept of bridging study and its strategies in clinical trials for new drug application.METHODS:The concept of bridging study proposed in the ICH E5 guideline was introduced,with a case using bridging strategies in the new drug applications(NDAs)approved by the regulatory authority in Japan.The concrete mode and the development of bridging studies in Asia were summarized.RESULTS:With the application of the ICH E5,some countries and regions have successfully used the bridging strategy in the new drug applications.The bridging strategy is becoming a common and practical basis for the decision making of marketing approvals of new drugs in the Asia-pacific country.CONCLUSION:The currently bridging studies in Asia will play an important role in the extrapolation of foreign clinical data in new drug application.Using bridging study is very helpful in judging ethnic differences of drugs,reducing duplication of clinical trails,as well as shortening clinical development periods.

Objective To observe the efficacy of imatinib on the treatment of bcr-abl positive essential thrombocythemia (ET). Methods A case of bcr-abl positive ET resistant to hydroxyurea (HU) treating with imatinib (200～400 mg/d) was reported and related literatures were reviewed. Results A case of bcr-abl positive ET was initially treated with 1.5～2.0 g/d HU, the platelet count decreased to 562x109/L after 4 weeks; however, the platelet count increased to (1020～1330)×109/L treating with same dose of HU 16 months later. With the elevation of HU to 3.0 g/d, platelet count was still high(1290～1780)x109/L companied with the very low white blood cell count(0.3～0.9)×109/L. While treating with imatinib (400 mg/d) for 1 month,the platelet count decreased to 390×109/L and white blood cell count was 0.5×109/L; Furthermore, treating with 200×300 mg/d of imatinib, the platelet and white blood cell count recovered in normal after 1 month,and bcr-abl fusion gene negative 2 months later. Conclusion Imatinib may be the effective targeting drug for the bcr-abl positive ET, and the bcr-abl positive ET is sensitive to low dose imatinib.

Objective To construct novel 3-D composite bionic network and evaluate the histocompatibility . Meth?ods The novel 3-D composite bionic network was prepared from chitosan, hydroxyapatite, gelatin and pectin in certain ra?tio by biomimtic approach, which was co-cultured with MC3T3-E1. The cell compatibility was studied by using inverted phase contrast microscope, routine paraffin section staining, scanning electron microscopy and F-DA staining. The resultant scaffold material was implanted into the dorsal subcutaneous space of SD rats. The histocompatibility, blood vessel capabili?ties and the degradation of the material were observed 2, 4, 8 and 12 weeks after surgery. Results The structure of novel 3-D composite bionic network was three-dimensional and porous. The cells attached on scaffolds attached and grew well with polygonal or fusiform form. It was found that inflammatory reactions were alleviated gradually in the early stage . There was an increasing angiogenesis at late stage. Materials degraded and absorbed more slowly. Conclusion The present study sug?gests that the novel 3-D composite bionic network has good histocompatibility with easy vascularization, and will be a candi?date scaffold for bone tissue engineering.

OBJECTIVETo evaluate remineralization efficacy of an arginine containing dentifrice on initial enamel carious lesions in vitro.

METHODSHuman enamel blocks with early lesions were prepared and randomly divided into three treatment groups: negative control group (distilled and deionized water), positive control group (fluoride containing dentifrice and 0.14% sodium monofluorophosphate), and test dentifrice group (8.0% arginine and 0.14% sodium monofluorophosphate). The lesions were subjected to a pH-cycling regime for 10 days. Surface enamel microhardness of the enamel blocks from each group was measured before and after pH cycling, and the surface microhardness recovery was calculated. Then, specimens were analyzed for enamel fluoride uptake (EFU) through acid etching method, after which they were treated in demineralization solution for a 2 h period of acid challenge. The other specimens were sectioned and examined through polarized light microscopy.

RESULTSIn the test dentifrice group, microhardness recovery and EFU were significantly higher than those in the negative control and positive groups. The test dentifrice group was significantly resistant to the acid challenge compared with the other groups. Conspicuous remineralization of enamel subsurface lesions was observed under polarized light microscopy among samples treated with test dentifrice, whereas the control groups showed no significant changes on enamel subsurface lesions.

CONCLUSIONThis study presents the potential superiority of Pro-Argin dentifrice over conventional fluoride dentifrice in promoting the remineralization of initial enamel lesions.

Arginine ; Calcium Carbonate ; Cariostatic Agents ; Dental Caries ; Dental Enamel ; Dentifrices ; Fluorides ; Hardness ; Humans ; Phosphates ; Tooth Demineralization ; Tooth Remineralization

Objective To investigate the prevalence of hypertension among adult residents in Mongolian region of Hulunbeier. Methods A total of 1536 adult residents were selected by using cluster sampling method, and 1496 completed the questionnaire survey. Blood pressure was measured for each participant. Results The prevalence of hypertension was 31.1%. Higher prevalence of hypertension was found in male ( 42. 0% vs 24. 5%, P ＜ 0. 05 ) and the elderly. No statistically significant difference of prevalence of hypertension was investigated in different nationalities (P ＞ O. 05 ). Conclusion The prevalence of hypertension among adult residents in Mongolian region of Hulunbeier is relatively higher.

Objective To investigate balanced steady-state free precession with flow-sensitive dephasing magnetization preparation (FSD-bSSFP) in the assessment of arteries of foot in diabetic patients.Methods The lower-extremity peripheral arteries of 43 diabetic patients were evaluated by FSD-bSSFP no contrast MRA and contrast-enhanced MRA (CE-MRA)in. Two experienced observers assessed the image quality, degree of venous contaminated and visibility of pedal artery branches by FSD-bSSFP and CE-MRA respectively in consensus. The signal intensity( SI), signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the source images of both groups were measured and Wilcoxon and t tests were performed. Results The image score of FSD-bSSFP group was 2.7 ± 1.1 and CE-MRA was 2.6 ± 0.8, there was no statistical difference ( Z = 0. 134, P ＞ 0. 05 ). The image score of demonstration of the pedal artery branches and degree of venous contamination on FSD-bSSFP were 3.2 ± 0. 9 and 1.8 ± 0. 4 respectively which were superior to that of CE-MRA (2.5 ± 0.9 and 2.1 ± 0.8 respectively). Significant statistical difference existed between the two groups in demonstration of pedal artery branches ( Z = 5.246, P ＜ 0.05 ) and degree of venous contamination (Z =2.541 ,P ＜0.05). SNR of FSD-bSSFP was 148.6 ±26.7, CNR was 88.3 ± 19.0. SNR of CE-MRA was 148.5 ± 45.6, CNR was 121.0 ± 41.0. No statistical difference existed between SNR between two methods (t = 0.013, P ＞ 0.05 ). But CNR of CE-MRA was superior to that of FSD-bSSFP and significant statistical difference existed between these two methods ( t = 5.113, P ＜ 0.01 ). Conclusion FSD-bSSFP without contrast could be used in the evaluation of foot arteries in patients of renal dysfunction and diabetes.

Objective To study the effect of low frequency on drug release from improved PLGA microcapsules, and investigate the possibility of utilizing PLGA microcapsules as the carrier of ultrasound targeted drug delivery system to deliver drug into brain. Methods Doxorubicin loaded poly (D,L lactic-co-glycolic acid) (PLGA) microcapsules were prepared via double emulsion solvent evaporate method and coated with either chitosan or gelatin. In vitro drug release profile and the drug release rate under the exposure of low frequency pulsed ultrasound (25 kHz) and continuous wave ultrasound (35.1 kHz) were assayed. Results The coating with chitosan or gelatin can depress the burst of drug release. The drug release rate from uncoated and chitosan-coated microcapsules did not changed with the exposure of ultrasound, and the rate of gelatin-coated microcapsules did increased. The effect of pulsed ultrasound was stronger than that of continuous ultrasound. Conclusion The drug release from gelatin-coated PLGA microcapsules can be controlled and triggered by 25 kHz pulsed ultrasound, which may be a potent carrier of targeting drugs into brain.

BACKGROUND:Fisher-Lewis rat kidney transplant models are the international common chronic renal alograft rejection models, but their application is greatly limited because of difficulty in model preparation and high costs. OBJECTIVE:To explore a new method of establishing SD-Wistar rat models of chronic renal alograft rejection. METHODS: Fifty-six pairs of SD-Wistar rats were subjected to left kidney orthotopic transplantation. The right kidneys of the recipients were intact and used as internal controls. 23 rat recipients were randomly divided into model group (n=15) and control group (n=8). The rats in the model group were injected with cyclosporine microemulsion for 10 days (2 mg/kg/day,i.p.) after kidney transplantation. The rats in the control group were not treated with immunosuppressive therapy. RESULTS AND CONCLUSION:The irreversible acute rejection occurred in al the transplanted kidneys of rats in the control group within 4 weeks, leading to the necrosis of transplanted kidney. Moderate inflammatory cel infiltration appeared in the transplanted kidneys of rats in the model group at 4, 8 and 12 weeks after transplantation. Typical histopathological changes of chronic rejection were observed within 12 weeks after transplantation. The Banff total scores were increased with time after transplantation. Al these histopathological changes were not observed in the intact right kidneys of rat recipients in both groups. The valey value of 

Objective: To understand the changes of smoking behavior among primary and middle school students in Beijing during 2005-2015. Methods: The primary and middle schools in Beijing were classified and then taken as a sampling frame. Twophase stratified random cluster sampling was conducted with school as primary sampling unit (PSU) and class as the minimum sampling unit, respectively. Beijing Schoolbased Smoking Monitoring Questionnaire was surveyed in 2005 and 2005, 2010, 2011, 2013 and 2015 anonymously. Results: In 2015, the smoking rate among primary and middle school students in Beijing was 9.41%. Among them, for primary, junior, high school and vocational high school students, the rates were 7.05%, 7.06%, 12.41% and 34.11%, respectively. The smoking rates were now 3.26%, with 1.99%, 1.80%, 3.48% and 20.22%, respectively, among primary, middle and high school and vocational high school students. male, vocational school students were more likely to report smoking across six waves of surveillance. Results from the surveillance in 2015 showed a decreasing trend in ever smoking rate and current smoking rate compared with previous survey. About half of the current student smokers were reported to take 1 cigarette/day, and about 10% smokers were reported to take 10 cigarettes/day. Students were most likely to smoke at home(24.02%), followed by smoking at schools(12.74%). The percentage of buying cigarettes by themselves was increased from 17.10% in 2008 to 66.09% in 2015. Conclusion From 2005 to 2015, both ever smoking and current smoking rate among middle school students in Beijing decreased in general, however smoking among vocational high school students warrants further attention.

Objective To retrospectively evaluate the safety ,technical success rate and long‐term efficacy of the hepatic mul‐tiple cavernous hemangioma with super selective arterial cheoembolization .Methods 6 cases multiple hepatic cavernous hemangio‐ma by clinical diagnosed between 2004-2011 years in our hospital ,Through arterial super selective and completely filling cheoem‐bolization by Pingyang mycin lipiodol emulsion(PYM‐Lip) ,To assess the long‐term efficacy .by multi slice spiral CT enhanced scan‐ning and carry on relevant statistics processing in postoperative 6 ,12 ,36months .Results 26 lesions were embolismed in 6 cases multiple hepatic cavernous hemangioma ,Among the number of successful embolization were 15 of 1 cases ,2 of 4 cases ,3 of 1 cases , respectively .26 lesions was decreased with different degrees ,which the diameter of lesions were reduced with embolismed by CT enhanced scanning in postoperative 6 ,12 ,36months and diameter reduced> 50% ,diameter reduced≤50% ,lesions disappear was 38% (10/26) ,54% (14/26) ,8% (2/26) ,62% (16/26) ,23% (6/26) ,15% (4/26) ,69% (18/26) ,12% (3/26) ,19% (5/26) .Technical operation success rate 100% ,not serious complications occurred .There are statistically significant differences in the size of lesions before and after operation(P<0 .01) .Conclusion The technique success rate was high ,minimally invasive ,the complications was less ,the curative efficacy was obvious by transcatheter arterial super selective cheoembolizaton with hepatic multiple cavernous he ‐mangioma .