Objective To study the inhibitory effects of radiotherapy and 125I seed brachytherapy on the growth of transplanted human lung cancer cell line A549 in nude mice and the impact of HIF-1αexpression after therapy.Methods Forty nude mice bearing human lung cancer cell line A549 were randomly divided into control group,radiotherapy group,125I seed brachytherapy group and radiotherapy + 125I seed group when tumor volume achieved (300±50) mm3.The tumor growth was observed and the alteration of tumor size was calculated at different time.On 15th day,the expression of HIF-1α was detected by immunohistochemistry and western blot.Results When eighth day after treatment,compared with the control group,the tumor volume of the combined treatment group was significantly smaller (t = 46.4,P ＜0.05).After fifteenth day after treatment,compared with control group,the group of radiotherapy,125I seed brachytherapy and radiotherapy + 125I seed gained the tumor control rate of 45.9 %,44.4 %,69.4 % respectively.Compared with other groups,the change of expression of HIF-1α in the combined treatment group was not significant (P ＞0.05).Conclusion Radiotherapy combined with 125I seed brachytherapy can inhibit the growth of transplanted human lung cancer cell line A549 in nude mice,and the tumor regression can be observed in early stage.But in our study,the expression of HIF-1α in tumors cannot be inhibited by 125I seed.

Objective To evaluate the effect of raltitrexed plus oxaliplatin combined with concurrent radiotherapy on life quality of advanced esophageal carcinoma.Methods Oesophageal cancer specific health related quality of life questionnaire(QLQ-OES18) was used to evaluate the life quality of 54 patients with esophageal carcinoma respectively at 1 day pre-treatment(baseline level),1 day post-treatment and 1month post-treatment.Total 54 patients were treated with raltitrexed plus oxaliplatin combined with con-current radiotherapy.Comparing the differences of quality of life scores at different time points,and analyzing the correlation of the differences between the 1month post-treatment and baseline score and short term effect.Results The scores of difficulty swallo-wing,eating difficulties,saliva decreased significantly at 1 day post-treatment than that of pre-treatment(P<0.05),the scores of eating pain increased significantly at 1 day post-treatment than that of pre-treatment(P<0.05)and there was no significantly differ-ences in other items(P>0.05).The scores of 1 day post-treatment were significantly reduced compared to baseline levels except re-flux and speech(P<0.05).It was positive correlation between the difference of 1 month post-treatment and baseline score and short term effect,and the correlation coefficients was 0.85,0.55,0.73,0.32(P<0.05),respectively.Conclusion There is a transient im-pact of raltitrexed plus oxaliplatin combined with concurrent radiotherapy on quality of life for advanced esophageal carcinoma after treatment,but most of the life quality of the patients could be improved after 1 month obviously.

Objective:To evaluate the efficacy and safety of raltitrexed plus oxaliplatin combined with concurrent radiotherapy for advanced esophageal carcinoma. Methods:A total of 54 patients with stageⅡ/Ⅲadvanced esophageal carcinoma according to the clinical staging of esophageal carcinoma nonsurgical methods were treated with raltitrexed plus oxaliplatin combined with concurrent radiotherapy. The patients were irradiated with a dose of 60 Gy in 30 fractions. Two cycles of concurrent chemotherapy were adminis-tered during radiotherapy, with 100 mg/m2 oxaliplatin and 2.6 mg/m2 raltitrexed on d1 and d22. Results:The complete response rate was 16.7%(9/54), and the partial response rate was 68.5%(37/54). The total response rate was 85.2%. The no response and progression rate was 14.8%(8/54). The one-and two-year local control rates and overall survival rates were 75.4%, 57.3%and 70.4%(95%CI, 0.6-0.8), 46.6%(95%CI, 0.3-0.6), respectively. The incidence rates of radiation-induced esophagitis, leucopenia, acute diarrhea, neuro-toxicity were 100%, 72.2%, 16.7%, and 44.4%, of which 7.4%, 7.4%, 1.9%, and 0%were≥grade 3, respectively. Conclusion:Ralti-trexed plus oxaliplatin combined with concurrent radiotherapy can enhance the response rate and prolong the survival of patients with advanced esophageal carcinoma. The regime has mild toxicity and is worthy of further study in PhaseⅢ.

Objective To investigate the radiosensitivity of stem cells in pancreatic adenocarcinoma PANC‐1 cell line and the possible mechanism of its radiation resistance .Methods Using flow cytometry ,the cells were isolated and sorted into CD44+CD24+ ,CD44-CD24+ ,CD44+CD24- ,and CD44-CD24- .Multi‐target click model was used to fit cell survival curves and deter‐mine the sensitizer enhancement ratio .The apoptosis and cycle distribution of the four cell subsets were determined using flow cy‐tometry ,and the level of ROS was determined by DCFH‐DA probe .Results The ratio of CD44+ and CD24+ in the sorted PANC‐1 cell line was 92 .0% and 4 .7% respectively .Before radiation ,there was no statistically significant difference between four groups (P>0 .05);After treated with 6MV‐X ray ,The ratio of apoptosis was the lowest in CD44+CD24+ (P<0 .01);The percentage G0/G1 cell was the highest in CD44+CD24+ (P<0 .01) ,the sensitizer enhancement ratio of CD44+ CD24- ,CD44-CD24+ and CD44-CD24- were 1 .61 ,1 .81 ,1 .94 ,respectively .The level of ROS in CD44+CD24+ was lower (P<0 .01) .Conclusion Tumor stem cells of pancreatic adenocarcinoma have properties of a lower level of ROS and relative stationary that maybe the reasons of radio resist‐ance .

Objective: To explore radiosensitivity-associated genes in esophageal squamous cell carcinoma by targeted sequencing panel. Methods: The peripheral blood from 22 esophageal squamous cell carcinoma (ESCC) patients received radiotherapy alone were collected, respectively. The genomic DNA (gDNA) of peripheral blood was extracted and used to create a library of gDNA restriction fragments. The gDNA restriction fragments were hybridized to the HaloPlex probe capture library, which comprises 356 cancer genes selected from the Catalogue of Somatic Mutations in Cancer (Cosmic) database of 2011 updated edition. The sequencing data were aligned by the Genome Analysis Toolkit GATK (version 3.0) and Picar. The single nucleotide polymorphism and inserted-deletion (SNP/InDel) variations were annotated by online database. The pathway enrichment was analyzed by Ingenuity Pathway analysis (IPA). Moreover, according to the short-period curative effect, 22 patients were divided into two groups: the radiation- sensitivity group (CR+ PR) and the radiation-resistant group (PD+ SD). The nonsynonymous mutation sites were statistically analyzed and the genes associated with radiosensitivity of ESCC were screened. Results: More than 97% sequencing reads were aligned to human genome reference sequence and more than 90% sequencing reads were the target sequences. SNP/InDel database annotation results showed that the mutations of 22 cases mainly distributed in exons, and the mutant types were mainly missense and synonymous single nucleotide variant (SNV). There were 23 genes of high-frequency mutation associated with esophageal cancer. Pathway enrichment by IPA showed that 3 pathways were associated with the development of esophageal cancer, which were roles of BRCA1 in DNA damage response pathway, DNA double-strand break repair by non-homologous end joining pathway and ATM signaling pathway. According to the curative effect, five genes including mismatch repair system component (PMS1), fibronectin 1(FN1), mutL homolog 1 (MLH1), B-Raf proto-oncogene, serine/threonine kinase (BRAF), patched 1 (PTCH1) and cytochrome P450 family 2 subfamily C member 19 (CYP2C19) were associated with radiosensitivity of ESCC patients.Moreover, the PTCH1 was mutated in all of 22 ESCC patients, while the variations of rs199476092 and rs202111971 sites of PTCH1 were only identified in the radiation-resistant group. Conclusions We find that the variations of rs199476092 and rs202111971 in the encoding region of PTCH1 gene are significantly associated with radiosensitivity of ESCC patients.

【Objective】 Diabetic mice could show learning and memory dysfunction, and we aimed to investigate the effect of Sigma-1 receptor agonist, PRE-084, on neurons and cognitive impairment in mice with type 1 diabetes (T1DM). 【Methods】 Twenty mice with T1DM induced by streptozocin, aged 8-10 weeks, and 20 control mice (CON) were randomly divided into four groups (CON+Vehicle, CON+PRE-084, T1DM+Vehicle and T1DM+PRE-084). Mouse primary neurons were cultured in high glucose medium with PRE-084 and control solvent, respectively. The body weight, food and water intake, and fasting blood glucose level of mice in each group were detected and recorded. The learning and memory abilities of mice were detected by new object recognition experiment. The mitochondria-associated endoplasmic reticulum membrane (MAM) structure of neurons in hippocampal CA1 area of mice was detected by transmission electron microscope. And the expression levels of ATP and reactive oxygen species (ROS) in hippocampus of mice were detected by biochemical kit. Cell viability and ROS level of primary neurons were detected by CCK8 and cellular ROS kit. 【Results】 PRE-084 reduced the increase of body weight, food and water intake, and blood glucose caused by diabetes. PRE-084 significantly ameliorated the learning and memory impairment of the mice with T1DM, improved the changes of MAM structure in neurons of hippocampal CA1 area of diabetic mice, increased the level of ATP in hippocampus of diabetic mice, and decreased the increase of ROS expression in diabetic hippocampus and neurons under high glucose conditions. 【Conclusion】 Sigma-1 receptor agonist, PRE-084, could improve learning and memory impairment in the mice with T1DM, which might be related to the structural changes of MAM, the increase of ATP production, and the decrease of ROS production in hippocampal neurons.

【Objective】 To explore the effect of cilostazol on intestinal barrier function in type 2 diabetes (T2DM). 【Methods】 The GSE142153 dataset was downloaded from GEO database to analyze gene changes in diabetic patients. Eight-week-old male db/db mice and control m/m mice were randomly divided into m/m+cmc, m/m+cilo, db/db+cmc, and db/db+cilo groups. Mice in different groups were given cilostazol and corresponding solvents for 4 weeks. We detected the levels of serum sCD40L and the expression of CD40 in intestinal tissue, and evaluated the mice’s intestinal barrier function by examining intestinal permeability, water content, bacterial number, and tight junction protein expression in different groups. 【Results】 Differential expressed genes were enriched in platelet activation and endothelial barrier function pathways in diabetic patients. Compared with those in the control group, the levels of serum sCD40L in db/db diabetic mice elevated significantly, and the CD40 expression, permeability, water content and bacterial number in intestinal tissue increased obviously, while the expression of tight junction protein decreased. Cilostazol treatment in diabetic mice decreased the levels of serum sCD40L and CD40, and alleviated significantly the intestinal barrier dysfunction. 【Conclusion】 Cilostazol attenuated the damage of intestinal barrier function in T2DM, and its protective effect may be related to the inhibition of platelet activation in diabetic mice.

【Objective】 To explore the effect of high-fat and high-fructose diet on mouse intestinal barrier function, as well as the role of ketohexokinase (KHK), the key enzyme in fructose metabolism, in intestinal barrier impairment. 【Methods】 Eight-week-old male control C57BL/6J mice and Khk^-/- mice were randomly divided into control + normal diet (ND), control + high-fat and high-fructose diet (HFHFD), Khk^-/-+ normal diet (ND+Khk^-/-), and Khk^-/-+ high-fat and high-fructose diet (HFHFD+Khk^-/-) groups, with eight mice in each group. During the high-fat and high-fructose diet and normal diet, the body weight changes of mice in different groups were recorded. After the intervention, the blood glucose and insulin levels of mice in each group were detected. The intestinal barrier function and inflammation level of mice were evaluated by detecting intestinal water content, permeability, tight junction protein expression, serum and intestinal inflammatory factor levels. 【Results】 Compared with ND group, HFHFD group significantly increased the body weight, blood glucose and insulin levels of mice, increased the intestinal water content and permeability, decreased the expression of tight junction proteins, and increased inflammatory factors of the serum and intestines. In the two groups fed with high-fat and high-fructose diet, the body weight, blood glucose and insulin levels of the HFHFD+Khk^-/- group were significantly lower than those of HFHFD group, and the intestinal barrier dysfunction and inflammation were significantly improved. 【Conclusion】 KHK, a key enzyme in fructose metabolism, is involved in the impairment of intestinal barrier caused by high-fat and high-fructose diet. Knockout of Khk gene significantly improved intestinal barrier dysfunction and the inflammation level.