Background:Gemcitabine is the first-line drug for chemotherapy of pancreatic cancer. However,owing to the inherent and acquired resistance,gemcitabine does not change obviously the prognosis of patients with pancreatic cancer. Exploration of the mechanism of acquired resistance to gemcitabine is of great clinical importance. Aims:To establish a gemcitabine-resistant human pancreatic cancer cell subclone and to explore preliminarily the resistance mechanism. Methods:Human pancreatic cancer cell line SW1990 was stimulated continuously with 0. 5 μmol/ L gemcitabine in vitro to establish the gemcitabine-resistant subclone SW1990-0. 5. The resistance index of SW1990-0. 5 cells was counted by CCK-8 assay. Proliferation and invasion of SW1990 and SW1990-0. 5 cells were detected by cell doubling time assay and scratch wound healing assay in vitro;cell cycle and cell apoptosis were detected by flow cytometry;expressions of multidrug-resistance related genes(MDR-1,MRP-1,and BRCP)and gemcitabine metabolic enzyme related genes(dCK,RRM1, and RRM2)were determined by real-time PCR. Results:The resistance index of SW1990-0. 5 cells was 9. 32. Compared with the parental SW1990 cells,the proliferation capacity but not the invasion capacity of SW1990-0. 5 cells in vitro was reduced. When treated with gemcitabine,the cell cycle of SW1990-0. 5 cells was similar to that of parental cells,whereas the cell apoptosis was significantly inhibited;expressions of MRP-1,BRCP and dCK mRNA were down-regulated,while expressions of MDR-1,RRM1 and RRM2 mRNA did not change. Conclusions:A stable gemcitabine-resistant human pancreatic cancer cell subclone SW1990-0. 5 was successfully established. Inhibition of cell apoptosis and down-regulation of dCK expression might contribute to the acquired resistance to gemcitabine of pancreatic cancer.

Background:Gemcitabine is the main drug for chemotherapy of advanced pancreatic cancer,however,the prognosis of pancreatic cancer patients has not been changed obviously because of the high innate and acquired resistance of cancer cells to gemcitabine. Aims:To investigate the correlation of DNA repair and expression of human APE1 / Ref-1(apurinic/apyrimidinic endonuclease 1 / redox factor-1),the key enzyme in base excision repair pathway,with the resistance of pancreatic cancer to gemcitabine. Methods:A gemcitabine-resistant human pancreatic cancer cell line SW1990-0. 5 with a resistance index of 9. 32 and its parental cell line SW1990 were treated with gemcitabine. DNA injury was assessed by comet assay. Expressions of APE1 / Ref-1 mRNA and protein were determined by real-time PCR and Western blotting, respectively. Results:In comet assay,after treated with gemcitabine for 24 hours,OTM value of SW1990-0. 5 and SW1990 cells were 0. 32 ± 0. 13 and 26. 96 ± 6. 83,respectively. Expression level of APE1 / Ref-1 mRNA in SW1990-0. 5 cells was 2. 48 ± 0. 49;and expression levels of APE1 / Ref-1 protein in SW1990-0. 5 and SW1990 cells were 1. 57 ± 0. 08 and 0. 84 ± 0. 06,respectively. Statistically significant differences were existed in all these parameters between SW1990-0. 5 and SW1990 cells(P all < 0. 05). Conclusions:DNA repair might be correlated with the resistance of pancreatic cancer to gemcitabine,and up-regulation of APE1 / Ref-1 might contribute to this resistance by its function on DNA repair.

Objective Corruption is the most common cadaver phenomenon in forensic practice and an important basis for inferring time of death(PMI),but the definition of corruption degree and the construction of model inference models have always been difficult in the practice of forensic science.Methods In this study,the late postmortem phenomena were observed.Meanwhile,the microbial flora structure of gut and gravesoil and the nature of gravesoil were detected,for analyzing the changes before and after the key moment of abdominal rupture which naturally happened during the cadaver decay.Results The results found that from the macroscopic and microscopic levels,there were significant differences in cadaver decay,including microbial flora structure and gravesoil properties before and after the key moment of the natural abdominal rupture during cadaver decay.The phenomena are highly observable and can be accurately judged by forensic examinations,as well as related means in the field of biology and physiochemistry.In this study,this critical event was called Rupture Point.Conclusion The Rupture Point can be used as an important node for the assessment of cadaver decay degree in the practice of forensic medicine.It can be utilized for a cut-off point as well when constructing PMI inference models based on microbial flora structure changes.The accuracy of PMI inference models can be improved when the models were constructed in segments.

Objective To explore whether the capacity of decision-making under ambiguity in adult patients with moyamoya disease(MMD)is impaired and its association with executive function.Methods Neuropsychological scales were used to measure the executive function of forty-one adult patients with MMD and forty-one healthy con-trols(HC),The Iowa Gambling Task(IGT)was utilized to study the capacity of decision-making under ambiguity of the two groups.Correlation analysis was performed between the two types of data.Results ① The total number of favorable choices in the MMD group was significantly lower than that in the HC group,with a statistically signifi-cant difference(Z=-2.782,P＜0.01),and the total number of unfavorable choices was significantly higher than that of the controls,with a statistically significant difference(Z=-2.782,P＜0.01).The results of ANOVA showed that the net residual value of Block4 and Block5 in MMD group was lower than that of Block4 and Block5 in HC group,respectively,and the differences were statistically significant(t=-3.433,P=0.001;t=-5.271,P＜0.001),the net residual value of Block 1 was higher than that of Block 1 in HC group,the difference was statisti-cally significant(t=2.715,P=0.008).② Spearman correlation analysis revealed no association between the net score of IGT,the total number of favorable choices,the total number of unfavorable choices,and executive func-tion.Conclusion The capacity of decision-making under ambiguity in adult patients with MMD is impaired possi-bly,which is not correlated with executive cognition.