OBJECTIVE:To provide reference information for continuous technological innovation of biopharmaceutical enterprises in China.METHODS:Based on theory of continuous technological innovation,we summarized the present situation of technological innovation in China's biopharmaceutical enterprises and analyzed the problems through the way of SWOT;fina lly we put forward the countermeasures.RESULTS&CONCLUSION:If biopharmaceutical enterprises want to develop and grow,they must unite related departments to construct the system of continuous technological innovation.

Objective To investigate the effects of the gene expressions of FAS、FASL、FADD and caspase-8 in esophageal carsinogenesis. Methods Immunohistochemical method was applied to detect the expression of FAS、FASL、FADD and caspase-8 proteins in esophageal epithelium. In situ hybridization method was applied to detect the expression of FADD and caspase-8 mRNA in esophageal epithelium. Results The positive rates of FAS, FADD and caspase-8 proteins and FADD、caspase-8 mRNA were decreased from normal epithelium to dysplasia and carcinoma tissues gradually. The positive rates of FASL protein were increased from normal epithelium to dysplasia and carcinoma tissues gradually. There was very significant statistical difference between carcinoma and normal epithelium(P

ObjectiveTo investigate the changes in the expression of T-cell death-associated gene 8(TD- AG8) in spinal cord in rats with bone cancer pain.MethodsTwo hundred and twenty-four female rats weighting 150-180 g were randomly divided into 3 groups:normal control group(group Ⅰ,n ＝ 64),normal saline group (group Ⅱ,n ＝ 64),bone cancer pain group(group Ⅲ],n ＝ 96).Bone cancer pain was induced by inoculating Walker256 mammary gland carcinoma cells into the tibia medullary cavity.Mechanical withdrawl threshold(MWT)was measured at 1 d before(baseline)and 1,3,6,9,12,15 and 18 d after inoculation.Sixteen rats were sacrificed at 1 day before(baseline)and 6,9,12,15 and 18 d after inoculation in group Ⅲ and 18 d after inoculation in groups Ⅰ and Ⅱ.The L4-6 spinal cord were removed,and the number of TDAG8 positive cell was counted,and the expression of TDAG8 mRNA was measured by RT-PCR.ResultsCompared with baseline value and group Ⅰ,MWT was decreased,and the number of TDAG8 positive cells and the expression of TDAG8 mRNA in spinal cord were increased at 6-18 d after inoculation in group Ⅲ ( P < 0.01 ).ConclusionThe expression of TDAG8 in spinal cord is up-regulated in rats with bone cancer pain,which may be involved in the mechanism of the development of bone cancer pain.

OBJECTIVE:To establish a method for simultaneous determination of tanshinol,caffeic acid,rosmarinic,salviano-lic acid B,salvianolic acid A,tanshinoneⅠ,cryptotanshinone,tanshinone ⅡA and ursolic acid in Compound xueshuantong cap-sules. METHODS:UPLC-MS/MS method was adopted. The determination was performed on ACQUITY UPLC? BEH C18 column with mobile phase consisted of acetonitrile-0.1%formic acid(gradient elution)at the flow rate of 0.2 mL/min. The column tempera-ture was 40 ℃,and the temperature of injector was 10 ℃. Analysis time was 7 min,and sample size was 5 μL. The electrospray ionization source(ESI)was used;ion source temperature was 150℃;capillary voltage was 3.5 kV;cone flow was 50 L/h;desol-vation temperature was 350 ℃;desolvation gas flow was 650 L/h;nebuliser pressure was 7 × 105 Pa;ion monitoring and multiple reaction monitoring (MRM) was performed. RESULTS:The linear ranges of tanshinol,caffeic acid,rosmarinic,salvianolic acid B,salvianolic acid A,tanshinoneⅠ,cryptotanshinone,tanshinone ⅡA and ursolic acid were 10.0-100.0 μg/mL (r=0.9998), 0.1-1.0 μg/mL(r=0.9998),4.0-40.0 μg/mL(r=0.9999),10.0-100.0 μg/mL(r=0.9999),15.0-150.0 μg/mL(r=0.9997), 8.0-80.0 μg/mL(r=0.9998),10.0-100.0 μg/mL(r=0.9997),50.0-500.0 μg/mL(r=0.9997)and 6.0-60.0 μg/mL(r=0.9998), respectively. The limits of quantitation were 40.0,9.6,38.0,88.0,130.0,39.0,4.4,3.2 and 10.0 ng/mL,separately. The limits of detection were 12.0,3.0,11.0,26.0,39.0,12.0,1.3,1.0 and 3.0 ng/mL,respectively. RSDs of precision,stability and repro-ducibility tests were all lower than 3%. The recoveries were 97.34%-103.20%(RSD=2.19%,n=6),97.22%-102.39%(RSD=2.03%,n=6),98.51%-101.70%(RSD=1.32%,n=6),97.86%-102.49%(RSD=2.09%,n=6),96.75%-103.12%(RSD=2.36%,n=6),98.43%-101.65%(RSD=1.25%,n=6), 97.59%-101.50%(RSD=1.50%,n=6), 96.45%-102.88%(RSD=2.58%,n=6),97.02%-103.11%(RSD=2.38%,n=6),separately. CONCLUSIONS:The method is simple and accurate,and can be used for simultaneous determination of 9 components in Compound xueshuantong capsules.

Objective To explore the correlationships between microperfusion diffusion indexes derived from intravoxel incoherent motion(IVIM)and perfusion values measured by arterial spin labeling (ASL)in renal allograft. Methods A total of 76 renal allograft recipients and 26 age-matched volunteers (group 0)were included in this prospective study. All subjects were underwent conventional MRI, IVIM and ASL MRI which were performed in the oblique-sagittal plane. Seventy-six recipients were divided into two groups based on the estimated glomerular filtration rate(eGFR):recipients with good allograft function(group 1, eGFR≥ 60 ml · min-1 · 1.73m-2,n=44)and recipients with impaired allograft function(group 2, eGFR<60 ml · min-1 · 1.73m-2,n=32). Three IVIM indexes values, including true diffusion coefficient(ADCslow), pseudo-diffusion coef fi cient(ADCfast), perfusion fraction(PF), and one ASL index value of renal cortex(renal blood flow, RBF)were measured. One-way analysis of variance and the least significant difference were used to compare the different of each cortical index values among three groups. Correlations between the ADCslow, ADCfast, PF, RBF and eGFR as well as the correlation among the indexes were evaluated using Pearson correlation coefficients. Results For cortical ADCslow, ADCfast, PF and RBF values, allografts with good function and impaired function showed significantly differences compared healthy controls(all P<0.01). In allografts with good function, cortical ADCslow,ADCfast,PF showed no significantly differences compared with controls(all P>0.05), but RBF value was significantly lower(P<0.05). The ADCslow, ADCfast, PF and RBF values of renal cortex were significantly lower in allografts with impaired function compared to allografts with good function(all P<0.01). In renal allografts, there were significant positive correlations between cortical ADCslow, ADCfast, PF, RBF value and eGFR(r values were 0.604, 0.552, 0.579 and 0.673, all P<0.01). Cortical ADCfast and PF value exhibited a significant correlation with RBF for recipients(r values were 0.501 and 0.423, all P<0.01). Conclusion Cortical ADCfast and PF values derived from IVIM and RBF measured by ASL show a significant positive correlation in renal allografts.

Ultraviolet radiation affects human health. On the one hand, moderate amounts of UV radiation can promote human health and have the effect of promoting vitamin D production; but on the other hand, excessive UV radiation can also cause adverse effects on human skin and eyes, such as causing skin photoaging, skin cancer, electrophthalmia and cataracts to occur. Therefore, the measurement of ultraviolet radiation is extremely important. This paper mainly reviews the health effects of ultraviolet radiation and the progress of measurement standards in the workplace, and puts forward suggestions on the revision of the existing standards from five aspects including use new measuring instruments and methods, improve the existing measuring instruments, specify the number of measurements, expand the scope of application of the standards and consider the influence of the sun on the measurement of artificial ultraviolet radiation, so as to provide reference for the revision of new standards.

Ultraviolet radiation affects human health. On the one hand, moderate amounts of UV radiation can promote human health and have the effect of promoting vitamin D production; but on the other hand, excessive UV radiation can also cause adverse effects on human skin and eyes, such as causing skin photoaging, skin cancer, electrophthalmia and cataracts to occur. Therefore, the measurement of ultraviolet radiation is extremely important. This paper mainly reviews the health effects of ultraviolet radiation and the progress of measurement standards in the workplace, and puts forward suggestions on the revision of the existing standards from five aspects including use new measuring instruments and methods, improve the existing measuring instruments, specify the number of measurements, expand the scope of application of the standards and consider the influence of the sun on the measurement of artificial ultraviolet radiation, so as to provide reference for the revision of new standards.

Objective This study compares a dual-freeze protocol with a triple freeze protocol for hepatic cryoablation in the Tibetan pig model.Method Cryoablation with a dual-(10-5-10-5 min)and triple-freeze (5-5-5-5-10-5 min) protocol for the normal livers of 9 Tibet pigs was performed under exposed operation.Temperature changes of cryoprobes and diameter changes of iceballs were measured during the ablation,and seven days later the pathological changes of cryozones were reviewed and the surface and depth cryolesions were measured.Results Compared with cryoablation with two freeze-thaw cycles,there was a greater iceball diameter for cryoablation by three freeze-thaw cycles.Also,seven days after cryosurgery,there were similar surface and deep cryolesions in dual-and triple-freeze protocols.Pathologically,the triple freezing protocol was associated with a longer zone of complete necrosis.Conclusions With the same freezing time (20 min),the triple-freeze protocol may become a more powerful liver-ablation method in cryosurgical application.

Objective:To explore the development, application and practical experience of investigator-initiated integrated clinical research information platform.Methods:The process of developing and constructing an integrated clinical research platform in a tertiary hospital in Beijing was introduced, the functions and advantages of the platform were described and displayed, and the main problems and risk points in the development and construction process were analyzed.Results:The integrated clinical research platform meets the management requirements of clinical research initiated by investigators, and the standardized management of the whole life cycle of the project can be realized through the platform, and the key issues of data security, information capture, sharing and interoperability need to be further explored in terms of platform docking.Conclusions:The integrated clinical research platform effectively improves the standardization, management quality and efficiency of investigator-initiated clinical research.

【Objective】 To understand the situation of free blood use of blood donors in Changsha to explore the correlation between free blood use of donors and repeated blood donation behaviors, so as to provide a theoretical basis for the recruitment of voluntary blood donations. 【Methods】 A total of 260 voluntary blood donors were selected by random sampling and divided into reimbursed group(n=97) and unreimbursed group(n=163), based on the results of a questionnaire, inquiring their using of free blood. 【Results】 The reimbursed group differed from the unreimbursed group in all dimensions, including behavioral attitude dimension(Z=3.250, P<0.05), subjective behavioral norm dimension(Z=4.576, P<0.05), and perceptual behavioral control dimension(Z=7.255, P<0.05) and the total score of the scale(Z=8.625, P<0.05), and the differences were statistically significant. 【Conclusion】 The intention to donate again was stronger in donors who experienced free blood use than those didn’t. Such donors are suitable candidates for blood donor recruitment. It is recommended to develop a suitable recruitment strategy for this population and further guarantee the clinical use of blood.