Objective To investigate the correlation of platelet activating factor(PAF)with cortisol(Cor) ,as well as their rela-tionship with patients after sepsis prognosis .Methods 102 patients with sepsis admitted in the ICU of Chongqing Emergency Med-ical Center from April 2012 to August 2013 were enrolled into sepsis group ,and 40 cases of volunteers served as control group .All the patients were divided into survival group and non-survival group ,according to their prognosis during hospitalization .Plasma PAF and Cor level in control group ,survival group and non-survival group were compared with each other ,and acute physiology and chronic health evaluationⅡ(APACHEⅡ)in survival group and non-survival group were compared .The correlations of plasma PAF with Cor level in control group ,survival group and non-survival group were analyzed ,respectively .Results Plasma PAF and Cor level in survival group and non-survival group were significantly higher than that in control group(P<0 .05) .Plasma PAF ,Cor lev-el and APACHEⅡ scores were higher in non-survival group than that in survival group(P<0 .05) .The correlation of plasma PAF with Cor level in control group was not significant(P>0 .05) ,while the plasma PAF level positively correlated with Cor level in survival group and non-survival group(P<0 .05) .Curves of receiver operating characteristics(ROC)showed that PAF ,Cor and A-PACHEⅡ score could be used as predictors of mortality during hospitalization(Area=0 .708 ,0 .715 ,0 .787) .Conclusion The plas-ma PAF level positively correlates with Cor level in patient with sepsis .PAF ,Cor and APACHEⅡ score have certain guiding signif-icance for the assessment of prognosis during hospitalization in patients with sepsis .

Objective To explore the effects and mechanism of S100A4 gene silence on invasion of human thyroid cancer cell. Methods After thyroid cancer cell ARO was transfected by S100A4 small interfering RNA (siRNA), mRNA and protein level of S100A4 and matrix metalloproteinase 2 (MMP-2) were determined by real time RT-PCR and Western blot respectively. The anchorage-independent growth was examined by colony formation assay in soft agar, and invasion ability was evaluated by boyden chamber model. Results The level of mRNA and protein of S100A4 was significantly inhibited in ARO cancer cells transfected by S100A4 siRNA.Transfection with S100A4 siRNA could inhibit anchorage-independent growth and invasion ability of thyroid cancer cell ARO in a dose-dependent manner. mRNA and protein expression of MMP-2 were down-regulated by S100A4 siRNA. Conclusion S100A4 siRNA can inhibit the invasion of thyroid cancer cell through down-regulation of MMP-2.

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 investigate the X ray radiation protective measure during interventional procedure.Methods The X ray radiation dose at 1,2,3 meters from the X ray tube in front of and in the near of lead glass,plumbic suit were measured in 101 cases interventional procedure.The data were analyzed and evaluated.Results The shielding efficacy was 95% by the lead glass and plumbic suit double protection,the X ray radiation was reduced markedly.The X ray radiation attenuation was swift with the distance increasing.The X ray radiation attenuation was 53.8% from 1 meter to 2 meter,and 81% to 3 meter.The X ray radiation received by medical personnel increased significantly with the fluoroscopy and subtraction time adding.Conclusion The X ray radiation protection should be carried out from shielding protection,distance protection and radiation time reducing;That can reduce the damage of radiation to keep the operator healthy.

This paper identified misunderstandings of the measures taken in China to overcome the problems incurred by off-label uses (namely reliance on drug makers to modify their medicine specifications,on medical institutions to enhance their regulation and management of off-label uses,and on informed consent to avoid risks).Based on such findings,the paper named defects found with such measures,and puts forward feasible ideas and methods to make such off-label uses legitimate and reasonable.These include clarification of the legal status of the medicine specifications,encouraging authoritative guidance for off-label uses,and determining the subject of evaluation to approve the off-label uses as reasonable.Such efforts aim at helping off-label uses out of the legal difficulties.

Objective To study the impact of TDGF-1 gene silience by small interfering RNA(siRNA)on the invasion and migration of human breast cancer cell. Methods 3 siRNA fragments were designed according to the characteristic of TDGF-1 gene sequence and the most appropriate siRNA was selected by fluorescence real-time quantitative RT-PCR method. After the human breast cancer cell line MDA-MB-468 was transfected by the selected TDGF-1 siRNA, mRNA and protein of TDGF-1 were determined by real time quantitative RT-PCR and western blot respectively. The migration and invasion ability of the cancer cell were evaluated by wound-healing assay and Boyden chamber model respectively. Results siRNA could down-regulate the level of mRNA and protein of TDGF-1 in a dose-and time-dependent manner. In vitro experiment showed that TDGF-1 siRNA transfection can effectively inhibit the clonal growth, invasion and migration of breast cancer cell in a dose-dependent manner. Conclusions TDGF-1 gene may play an important role in the migration and invasion of human breast cancer cells. siRNA transfection can inhibit the invasion of human breast cancer cells.

Objective To study effects of polo-like kinase-1(PLK1)small interfering RNA(siRNA)on proliferation and apoptosis of undifferentiated human thyroid cancer cells.Methods 5 PLK1 siRNA(S1,S2,S3,S4 and S5)were constructed and used to transfect human thyroid cancer cell line ARO.RT-PCR was employed to pick out the most effective siRNA,which was then used to transfect ARO cell.RT-PCR and western blot were used to detect PLK1 expression in thyroid cancer cells,which were divided into different groups.MTT assay was performed to examine the effects of PLK1 siRNA on thyroid cancer cells in all groups.Apoptosis of thyroid cancer cells was observed by caspase-3 activity and TUNEL.Results All the 5 siRNA down-regulated PLK1 mRNA expression.among which S4 showed the best effect.S4 transfection could obviously inhibit proliferation of thyroid cancer cells in dose and time dependent manner.Compared with control groups,caspase-3 activity of cancer cells in s4 transfeeted group increased significantly.The effect of S4 transfection was dose and time dependent.TUNEL results showed apoptosis of cancer cells transfected by S4 siRNA was obvious and apoptosis of cells was dose-dependent.Conclusions PLK1 may play an important role in proliferation of undifferentiated thyroid carcinoma.PLK1 siRNA transfection can inhibit proliferation of throid cancer cell through apoptosis induction.

Objective To establish a CVS-11 pseudovirus particles ( pp)-based assay for detec-tion of neutralizing antibody against rabies virus. Methods An improved rapid fluorescence focus inhibition test ( RFFIT) for detection of neutralizing antibody against rabies virus ( RVNA) was established based on the CVS-11 pseudovirus expressing a luciferase reporter gene. Forty-six human serum samples were analyzed with the improved RFFIT and the results were compared with those by using standard RFFIT. Moreover, the improved RFFIT was used to detect the titers of RVNA in 91 serum samples collected from pet dogs and pet-breeders in Beijing. Results The coincidence rate of the improved RFFIT and the standard RFFIT was 100% regarding to the analysis of 46 human serum samples and 5 negative reference serum samples. Moreo-ver, the RVNA titers of all serum samples obtained with CVS-11 pseudovirus-based assay showed a signifi-cant high correlation with those obtained with standard RFFIT (n=46, r=0. 94, P<0. 000 1). All of the 91 serum samples collected from pet dogs and pet-breeders in Beijing were positive for RVNA as indicated by the improved RFFIT with a mean titer of 33. 01 IU/ml. Conclusion We established an improved RFFIT based on the CVS-11 pp expressing luciferase reporter gene, which might be used as a reliable alternative RFFIT for measuring RVNA titer. Analysis of the 91 serum samples collected in Beijing with the improved RFFIT showed that all samples were positive for RVNA.

Objective To evaluate the effect of MRI in reflecting the pathological changes of VX2 carcinoma in rabbits after radiofrequency ablation (RFA) . Methods RFA was performed in the livers of 24 rabbits with planted VX2 carcinoma. The rabbits were divided into 4 groups. After RFA, the rabbits were killed after MR imaging on 0, 1, 2, and 4 weeks, respectively. The correlation between MRI and pathological findings was analyzed. Results In the acute phase, coagulative necrosis of the ablated tumors and inflammatory reaction with hyperemia around were detected at microscopic examination. The ablated tumor showed as hypointensity on T1WI and hyperintensity on T2WI, while rim of high signal intensity on T1WI and low signal intensity on T2WI was found. Gadolinium-enhanced MRI showed a thin high signal rim surrounding the central coagulative necrosis. In the subacute phase, extensive coagulative necrosis and marked infiltration by neutrophils, lymphocytes, macrophages and a peripheral fibrous generation rim were observed microscopically on the ablated tumor. The ablated tumor showed iso-or hyperintensity on T1WI and hypointensity on T2WI, while the periphery of ablated lesions was hypointensity on T1WI and hyperintensity on T2WI. There was prominent rim enhancement along the ablated margin. In the chronic phase, peripheral fibrous rim became obvious, more regular and thicker than at subacute phase as hypointensity on T1WI and T2WI, and unenhancement was observed. Residual or recurrence of tumor was found in 17 rabbits as hypointensity on T1WI and hyperintensity on T2WI, and irregular, thicker rim or nodular enhancing abnormalities. Conclusion MRI can effectively show the histopathological tissue changes of rabbit VX2 carcinoma after ablation and demonstrate the residual or recurrence of tumor.

Objective To assess the memory function of hyperthyroid patients at different disease durations and investigate the value of cerebral blood flow (CBF) imaging in the detection of memory dysfunction in related regions.Methods Thirty-seven hyperthyroid patients (10 males,27 females; mean age (39.27± 10.58) years) and 28 healthy volunteers (8 males,20 females; mean age (35.80±9.41) years) were enrolled into this prospective study.The patients were divided into two subgroups: short duration group (duration ≤ 6 months; n =15),long duration group (duration ＞6 months ; n =22).Wechsler memory scale was used for memory assessment,and cancellation test was used for attention assessment.Self-rating depressions scale (SDS) and self-rating anxiety scale (SAS) were used for mood disorder assessment.99Tcm-ECD SPECT CBF imaging was performed at rest for all patients and controls on the same day.SPM 2.0 was used to investigate the differences of rCBF between the two groups.Two independent samples t test was used for the comparisons of memory and attention scores between patients and controls,also between patients with short and long disease durations.Multiple stepwise regression was used for factor analysis of memory state.Results Scale total score (92.27±17.50 vs 101.75±11.70; t=-2.476)and memory quotient (91.32±17.76 vs 100.29±9.43 ; t =-2.421) were significant different between patients and controls (both P＜0.05).The scale total score and memory quotient in patients with long disease duration were significant lower than those of controls(88.77±16.69 vs 101.75±11.70,t=-3.231; 86.18±16.73 vs 100.29±9.43,t=3.770,both P＜0.05).The memory quotient was significant lower in patients with long disease duration than those with short disease duration(86.10± 17.13 vs 98.87± 17.00; t =2.212,P＜0.05).There was no significant difference in memory quotient and scale total score between short duration group and controls (t=-0.754,0.910,both P＞0.05).CBF was reduced in the limbic system of hyperthyroid patients and the involved area was larger in patients with long disease duration.Age,attention score,serum FT4 level and reduced CBF in left pulvina nuclei,left lateral geniculate body and right amygdale were the statistically significant factors for impaired memory function in hyperthyroid patients (b=-0.393-0.685,all P＜0.05).Conclusions Memory impairment could be significant in hyperthyroid patients with long disease duration.CBF imaging could reflect the degree of dysfunction at specific brain regions responsible for memory impairment in these patients.