Pharmaceutical excipients are implementing registration and approval management in our country. As the disadvantages of the registration system appearing continuously, the demand for reform is getting higher and higher. The cry for drug master files ( DMF) model instead of registration and approval management is becoming more prominent. Based on the understanding of DMF sys-tem, the article discussed the positive roles of the excipients standards and guidelines construction in DMF implementation using phar-maceutical excipients supervision experience in the United States as the reference and starting from the standards and guidelines system of excipients, which aimed to provide suggestions for the supervision and management of pharmaceutical excipients, and improve the quality and safety of pharmaceutical excipients and drugs.

OBJECTIVE: In order to understand the effect of stimulator of Fe transport(SFT) on Fe metabolism and its abnormality(absence or overloading),this study reviews the research development of SFT at home and abroad and focused on the relationship among expression,structure,physiological function,expressing controlling and expressing abnormality with brain iron metabolism.DATA SOURCES: Electronic literature search of NCBI related to SFT was performed using the terms "stimulator of iron transport" or "stimulator of Fe transport",and the language was restricted in English. And simultaneously CNKI database was searched with the word "brain iron metabolism" and"stimulator of Fe transport" in Chinese from January 1997 to October 2004.STUDY SELECTION: Articles that reported the structure,expression regulation of SFT and its relationship to brain iron metabolism diseases were included.DATA EXTRACTION: Twenty pieces of SFT-related literatures and 1300pieces of literatures related to brain iron metabolism were found,among which 21 pieces were included.DATA SYNTHESIS: From the 21 pieces of literatures,the structure,distribution,biological function,expression regulation of SFT and its relationship with brain iron metabolism were mainly discussed.CONCLUSION: SFT can stimulate both transferrin- and nontransferrin-bound iron uptake. The expression of SFT can be regulated transcriptionally and post-transcriptionally,mainly regulated in response to different cellular iron levels. So SFT plays an important role in brain iron metabolism.

Objective To investigate the mechanisms of oridonin inducing apoptosis on acute leukeamia NB4 cells and its mechanism. Methods NB4 cells in culture medium in vitro were given with different concentrations (8, 16, 24, and 32 μmol/L) of oridonin. The inhibitory rate of the cells was measured by MTT assay, cell apoptotic rate was detected by flow cytometry (FCM), morphology of apoptosis was observed by Hoechst 33258 fluorescence staining, DNA fragmentation was assayed by agarose gel electrophoresis, caspase-3 expression was detected by Western blotting, and caspase-3 activity was assayed with colorimetric assay kit before and after apoptosis occurred. Results Oridonin (over 16 μmol/L) could inhibit the growth of NB4 cells and cause apoptosis significantly, the suppression was both in a timeand dose-dependent manner. Marked changes of apoptosis including condensation of chromatin and nuclear fragmentation were observed very clearly by Hoechst 33258 fluorescence staining and a characteristic "ladder" of DNA fragments was elicited by agarose gel electrophoresis; Western blot analysis revealed that caspase-3 was activated by the loss of caspase-3 proenzyme (32 kDa) and the appearance of its 20 kDa subunit, and that along with the apoptotic process caspase-3 activity was increased concurrently. Conclusion Oridonin can induce apoptosis in NB4 cells via activation of caspase-3. These results will provide laboratory evidence for the clinical treatment of acute leukemia with oridonin.

Tuberculosis(TB)is an infectious disease caused by Mycobacterium tuberculosis(MTB).Autophagy plays an im-portant role in eliminating MTB which can interfere with host autophagy through a variety of mechanisms,therefore,escape the killing of macrophages to survive and reproduce in the host cells for a long time.There are many kinds of differential expressed non-coding RNAs(ncRNAs)in macrophages upon MTB infection.These ncRNAs can affect the elimination of MTB by regula-ting the expression of autophagy-related genes in multiple processes of autophagy.Elucidating these regulatory networks are of great significance for the development of new anti-TB drugs.Therefore,the known mechanisms of ncRNAs that regulates the autophagy of MTB infected macrophages were summarized,and the process of autophagy and the main regulatory functions of ncRNAs were introduced in this review,in order to provide new perspectives for the pathogenesis of TB and the development of anti-TB drugs.

Objective To present and discuss beam characteristics of the first Mevion S250i gantry-mounted accelerator pencil beam scanning proton therapy system in China.Methods The output dose was measured using a parallel-plate ionization chamber.The integrated depth dose was measured with a large-radius Bragg peak ionization chamber,covering 19 energy levels ranging from 227 MeV to 28 MeV,to analyze the proton beam characteristics.The spots in the air were measured with Phoenix flat panel detector on the beam central axis,and the precision of the delivery position was verified by measuring the multi-spot beam map.The interleaf leakage and penumbra reduction of adaptive aperture were measured to characterize its performance.Results The proton system was calibrated for a maximum energy of 227 MeV,with a(10×10)cm2uniform field delivering 1 Gy dose at a depth of 5 cm underwater.The system effectively modulated the proton beam range to the patient's surface,maintaining a constant 80%-80%Bragg peak width of 8.6 mm at all energy levels.The spot size of the highest energy beam at the isocenter was about 4 mm in the air,and the spot delivery position error was less than 1 mm.The interleaf leakage rate of the adaptive aperture for the highest energy beam was below 1.5%,and the penumbra was significantly reduced.Conclusion Mevion S250i proton therapy system demonstrates unique design and beam characteristics,which is reflected in the Bragg peak shape,spot size variation with energy,and penumbra sharpening of adaptive aperture;and these differences should be considered in treatment planning system modeling and planning for precision treatment.

Objective:To measure and assess relevant radiation doses at the radiotherapy site of the first domestic single-vault proton therapy system.Methods:The radiation levels of the therapy system during and after beam irradiation were measured, and annual effective doses were assessed for personnel at the site.Results:During beam irradiation, the highest radiation dose was detected at the shielded door of the equipment floor, with a gamma radiation level of 2.140 μSv/h and a neutron radiation level of 0.850 μSv/h. Neutron radiation disappeared immediately once the beams stopped. In contrast, the radiation activated originated mostly from gamma rays. A longer time after beams stopped was associated with lower induced radiation intensity at the same location. Furthermore, a farther distance from the irradiated object corresponded to lower induced radiation intensity at the same time. The assessment result reveal that the annual effective doses to the personnel were at the safe level, with physicists exposed to the highest dose of 2.138 mSv.Conclusions:The radiation level at the studied proton therapy site meets the safety requirement, and the treatment can be performed safely at this site.