Objective:To investigate the mechanism of endoplasmic reticulum (ER) stress-induced chemoresistance to cisplatin in gastric cancer cells. Methods:ER stress models were established in both BGC823 and SGC7901 gastric cancer cells. The expression of GRP78, an ER stress marker, was examined by Western blot analysis. Moreover, whether ER stress can decrease the sensitivity of gastric cancer cells to cisplatin and activate P38 was explored by flow cytometry and Western blot analysis, respectively. Whether ER stress-induced chemoresistance to cisplatin can be abrogated by blocking P38 activity in gastric cancer was also elucidated using flow cytometry. Results:GRP78 protein expression markedly increased after treating BGC823 and SGC7901 gastric cancer cells with tunica-mycin (TM) or thapsigargin (TG) for 8, 16, and 24 h (P<0.05), compared with that in the group treated for 0 h. The apoptotic rates of TM-(or TG)-, cisplatin-, and TM (or TG) plus cisplatin-treated groups significantly increased (P<0.05) in both BGC823 and SGC7901 gastric cancer cells compared with the rate in the control group. The apoptotic rate of TM (or TG) plus cisplatin-treated group signifi-cantly decreased (P<0.05) in both BGC823 and SGC7901 gastric cancer cells compared with that of the cisplatin-treated group. Com-pared with the group treated for 0 h, phospho-P38 expression markedly increased after treating BGC823 and SGC7901 gastric cancer cells with TM (or TG) for 8, 16, and 24 h (P<0.05). No difference in P38 protein expression was observed between each group in both BGC823 and SGC7901 gastric cancer cells (P>0.05). Both P38 inhibitors, either SB203580 or PD169316, can inhibit the activation of P38. The inhibition of P38 activity can overcome ER stress-induced chemoresistance to cisplatin in gastric cancer cells (P<0.05). Con-clusion:ER stress can trigger the chemoresistance to cisplatin by activating P38 in gastric cancer cells.

Objective This study is to evaluate the advantages between percutaneous and peratrial device closure of secundum atrial septal defects(ASD) under single transesophageal echocardiographic (TEE) guidance.Methods From December 2010 to December 2012,53 patients with the ASD of≤25 mm in diameter underwent percutaneous device closure under simple TEE guidance(the percutaneous group).The device was implanted through the femoral vascular access.Fifty patients with similar age and similar-sized ASD to the percutaneous group,were selected from 350 consecutive patients who underwent peratrial device closure of ASD and assigned to the peratrial group.The ASDs were occluded through a right minithoracotomy approach.The success rate,intracardiac manipulation time,procedural time,postoperative stay and the follow-up results were recorded.Results When the maximum diameter of ASD was ＜ 20 mm,the success rate of both groups was 100％.When the ASD diameter was 20 mm but 25 mm,the success rate was 84％ in the percutaneous group and 100％ in the peratrial group.Three patients failed in the percutaneous group with the ASD diameter of 20 mm and the aortic rim of 3 mm.They were successfully converted to peratrial device closure.The average intrcardiac manipulation time was(20±7) minutes in the percutaneous group and (5 ± 6) minutes in the peratrial group(P ＜ 0.05).The average procedure time was(24 ± 7) minutes in the percutaneous group and (39 ± 6) minutes in the peratrial group(P ＜ 0.05).The postoperative hospital stay was (3.0 ± 0.8) days in the percutaneous group and(4.7 ± 1.5) days in the peratrial group(P ＜ 0.05).Conclusion The percutaneous device closure of ASD under simple TEE guidance is feasible,safe,and efficacious in patients with the ASD diameter of ≤25 mm.It has the advantages of less trauma,less procedural time,shorter hospital stay and better cosmetic results.However,when the ASD diameter was 20 mm and the aortic rim was 3 mm,the peratrial approach may be a better choice.

Objective To study the efficacy and the safe dosage of high intensity focused ultrasound (HIFU) ablation in pancreatic cancer.Methods From November 2010 to May 2013,21 patients with advanced pancreatic cancer were treated by HIFU at the First Affiliated Hospital of Zhengzhou University.These patients who were randomly divided into two groups (10 and 11 patients respectively),were given a low-power (100～249 W) treatment and a high power (250 ～350 W) treatment.These two groups of 21 patients received a total of 25 times of HIFU treatment (3 patients received twice of low-power treatment,while 1 patient received twice of high-power treatment).The two groups were compared by analyzing the treatment parameters (average power,total treatment time,treatment total energy,treatment volume,etc.) and volume of tumour response as shown on postoperative imaging (CT or MRI) examinations.Also,the complications,degree of pain relief and survival were compared.The energy efficiency factor (EEF) and the ablation ratio were calculated.A preliminary study was conducted on the relationship of the ultrasound dose and the ablation effect of HIFU treatment for pancreatic cancer.Results (1) The EEF of the high-power group (≥250 W) and the low-power group (＜ 250 W) were (10.39 ± 5.71) J/mm3 and (21.62 ± 9.81) J/mm3,the former group was significantly lower than the latter group (P ＜0.05) ; the ablation ratio of the high-power group was higher than the low-power group,(91.52 ± 4.18)％ versus (51.59 ± 7.66)％ respectively,the difference was statistically significant (P ＜ 0.001).(2) The efficiency factor and the ablation volume for the HIFU treatment showed a linear trend,and both were negatively correlated (Pearson correlation coefficient r =-0.485,P ＜ 0.05).(3) There was no serious complication after the HIFU treatment.In the low-power group,six of ten patients were alleviated of his pain (60％) ; the CA19-9 decreased in four of ten patients after HIFU treatment (40％).In the high-power group,nine of eleven patients were significantly relieved of pain after treatment (82％),the CA19-9 decreased in five of nine patients after HIFU treatment (56％).(4) On Kaplan-Meier survival analysis,HIFU treatment of patients with pancreatic cancer,the median survival was 8 months and 9 months in the low-power group and high power group,respectively (Log-rank test x2 =0.05,P =0.944).Conclusion During HIFU treatment of patients with pancreatic cancer,if the ultrasound power was between 250 W and 350 W,there was a higher proportion of tumor ablation,but with no serious complications.Thus,this dose was safe.

Objective To investigate the effects of RNA interference targeting EphA7 gene on the growth of SMMC-7721 cell xenograft in nude mice.Methods Recombinant plasmid of EphA7 gene-targeting siRNA was transfected into hepatic cancer SMMC-7721 cells by LipofectamineTM2000,comparing with the empty vector transfected group,untransfected group and control group.The nude mice tumor model was established by subcutaneous injection of hepatic cancer cells in the left upper limb of the mice.Control group was injected with PBS as blank.Real-time PCR,immunohistochemistry and Western blot were employed to detect the mRNA and protein expressions of EphA7 in tumor tissues.The tumor formation time,tumor mass and weight of tumor were also considered in the analysis.Results About 9 ～ 12 days after the injection of tumor cells,the xenograft tumor formation can be observed around the injection site except the control group.35 days after tumor formation,there were obvious decreases in the tumor growth rate,tumor mass,as well as tumor weight in transfected group,comparing with empty vector transfected group and untransfected group (P ＜0.05).Transfection of RNA interference can inhibit the growth of xenograft tumor by 55％.Immunohistochemistry tests showed that there were less cells with positive staining of EPHA7 protein in transfected group,and the staining was lighter as pale yellow,in contrast with the untransfected group and the empty vector transfected group.Real-time PCR and Western blot revealed that the expression of EphA7 mRNA and EPHA7 protein of transfected group were significantly lower than those of untransfected group and empty vector trausfected group with statistically significance (P ＜ 0.05).Conclusion Silencing EphA7 gene with RNA interference can effectively inhibit the growth of SMMC-7721 cell in nude mice,which is expected to become a new target for gene therapy of hepatic cancer.

Objective To study the efficacy and safety of high intensity focused ultrasound (HIFU) treatment for advanced pancreatic cancer.Methods In this study,25 patients with advanced pancreatic cancer received high-intensity focused ultrasound (HIFU) treatment.Liver and kidney function,CA19-9 levels,tumor size changes,pain relief,survival rate before and after treatment were evaluated.Results The blood routine test,liver and kidney function,blood amylase did not alter significantly after HIFU treatment in all patients.The CA19-9 level of 12 patients decreased.The appetite of 15 patients improved,5 patients with body weight gain after HIFU treatment.Pain was relieved after HIFU treatment in 18 cases,pain relief rate was 72％ (18/25).In 15 cases tumor ablation volume ＞ 90％ after HIFU treatment,5 patients with tumor ablation volume ＞ 50％,tumor ablation effective rate was 80％ (20/25).There were no major complications such as acute pancreatitis,gastrointestinal injury after HIFU treatment.After HIFU treatment,the median survival period was 8 months,1 year survival rate was 30％.Conclusions High-intensity focused ultrasound is a safe and effective method of palliative treatment for advanced inoperable pancreatic cancer.

Objective Toinvestigatetheexpressionof SIRT1anditsassociationwith clinicopathologic features in breast carcinoma with type 2 diabetes mellitus.MethodsThe expression of SIRT1 in 30 breast cancer with type 2 diabetes mellitus,65 samples of breast cancer without diabetes mellitus and 18 samples of corresponding normal breast tissues was investigated using immunohistochemistry.ResultsThe positive rate of SIRT1 in breast cancer tissues was significantly higher than that breast cancer with type 2 diabetes mellitus and normal breast tissue (P ＜0.05). In breast cancer with type 2 diabetes mellitus group.The positive rate of SIRT1 was significantly higher than that normal breast tissue(P ＜0.05).The expression of SIRT1 was positively correlated with the number of lymph node(P =0.011),pTNM tumor stage (P =0.028), p53 (P =0.003) and Her-2 (P =0.031) in breast cancer with type 2 diabetes mellitus group. The expression level of SIRT1 in lymph node-positive group was higher than that in lymph node-negative group (P ＜0.05).The expression level of SIRT1 was in lymph node-positive group was higher than that in lymph node-negative group(P ＜0.05).ConclusionSIRTI was up-regulated in breast cancer with type 2 diabetes mellitus,but its expression was lower than that breast cancer without diabetes mellitus,and was associated with the progression of diabetes mellitus. SIRT1 was positively correlated with lymph node, pTNM tumor stage,p53 and Her-2, SIRT1 may be a novel biological parameter to evaluate the malignant degree of breast carcinoma and to predict prognosis of breast cancer.

Objective To prepare monoclonal antibody(mAb) against CUE domain containing 2(CUEDC2) protein and detect the expression level of CUEDC2 in mouse tissues.Methods Fusion protein GST-human CUEDC2(hCUEDC2) was expressed and purified,and mAb against CUEDC2 was prepared by using hybridoma technique.The specificity of the antibody and CUEDC2 expression in mouse tissues were detected by Western blot analysis.Results We obtained mAb against CUEDC2 protein,which recognized specifically both hCUEDC2 and mouse CUEDC2.The mAb could be used to detect expression level of CUEDC2 protein,which was different in various mouse tissues.Conclusion The prepared CUEDC2 has good mAb specificity and can be used to detect expression of CUEDC2 protein in mouse tissue,thus providing a useful tool for further investigation into the functions of CUEDC2.

Objective: Epithelial dysplasia of the esophagus and gastric cardia is precancerous lesion, including mild, moderate and severe levels. In 2000 year, WHO recommended to replace dysplasia with intraepithelial neoplasia. Mild and moderate dysplasia were classified as low-grade intraepithelial neoplasia (LIN). Cardia adenocarcinoma was suggested to be called esophageal-gastric junction adenocarcinoma. The risk of cancer development and the rule of time evolution were detected in esophagus and esophageal-gastdc junction LIN in high incidence area of esophageal cancer in Northern China, in an effort to provide scientific data for the prevention of esophageal cancer. Methods: Between October 2001 and October 2002, two townships of Cixian were chosen to carry out endoscopic iodine staining screening cohort study. The total population aged 0-85 was 22,016, of which 6,596 aged 40-69 (3257 males and 3339 females). Except for thoese with contraindications and those who refused to join the study, 3,506 cases were finally recruited in the study, and the screening rate was 53.2%. According to WHO criteria of the pathological diagnosis, the esophageal squamous epithelium with mild and moderate dysplasia and esophageal-gastric junction with mild dysplasia were classified into LIN groups (including 616 cases). The control group contained a total of 2,478 cases without precancerous lesions and free of cancer in endoscopic screening. Results: From June to September in 2008, the cohort was followed up and 174 cases were lost, with a follow-up rate of 95.0%. Follow-up was 3,970.7 person- years in the LIN group and 16,120.0 person-years in the control group.Carcinomous conversion rates were 251.7 and 68.2/per 100,000 person- years respectively in the LIN group and the control group. The median time in the two groups was 38 and 47 months, respectively. Compared with that of the normal population, the relative risk (RR) of LIN was 3.69 (95% CI=1.57-8.69, P=0.001). Conclusion: Population with LIN are at high-risk for esophageal cancer and endoscopic examination every year is absolutely necessary.

A high performance liquid chromatography tandem mass spectrometric ( HPLC-MS/MS ) method was developed for the determination of seven perfluorinated alkyl acidin ( C4-C10 ) and perfluorooctane sulfonate in water. After the particulate was removed by leaching, surrogate standard was added, then the sample was loading to a pre-conditioned WAX cartridge for purification, and then the eluent was concentrated and analyzed by HPLC-MS/MS. Due to the situation that the fluoride polymer was unavoidable to be used in the LC system, a delay column was employed and the perfluorooctanoic acid ( PFOA ) of interference was departed from the PFOA in sample. The method detection limit ( MDL) of PFOA was 0. 8 ng/L, and the lowest quantitative concentration (LQC) was 3. 2 ng/L. For other compounds, the MDL was ranged from 0. 2 to 1. 2 ng/L, and the LQC was 0. 8-4. 8 ng/L. This method also had good reproducibility, for six duplicated samples, the relative standard deviations ( RSD ) of all target compounds were less than 16%. And the recoveries of target compounds at six spiked matrix samples ranged from 87% to 129%, and the RSD were less than 15%. Because of the connection of delay column, the background was well controlled, and a relatively lower MDL were obtained.

Objective To investigate the feasibility,effectiveness,and technical superiority of Solumbra thrombectomy for treatment of acute large cerebral artery occlusion stroke.Methods 32 patients who had acute large cerebral artery occlusion stroke and received mechanical thrombectomy in TEDA Hospital of Tianjin between January 2013 and August 2016,were divided into two groups:stent group(with conventional stent-retrievers,n=21) and Solumbra group (with Solumbra thrombectomy,n =11).Clinical characteristics,variables correlated with operation,and clinical outcomes were compared and analyzed retrospectively.Results There were no differences in basic clinical and radiographic parameters between stent group versus Solumbra group (all P＞0.05).Moreover,there were no differences between Solumbra group versus Stent group in rates of embolus to new territory(18.2 ％ vs.28.6％,P=0.425),in times of thrombectomy(2.2± 1.0 vs.2.4± 1.3,P=0.657),in nonsymptomatic intracranial hemorrhage (18.2％ vs.14.3％,P =0.572),in symptomatic intracranial hemorrhage(18.2％ vs.9.5％,P =0.427),in TICI 2b/3 revascularization(81.8％ vs.81.0％,P =0.670),in puncture-to-reperfusion time[(66.4±39.0)min vs.(51.6±34.5)min,P=0.279],and in NIHSS at 7 days(11.6 ± 7.7 vs.11.3 ± 7.2,P =0.925).A modified Rankin Scale(mRS ≤2) is a variable of recovery of function and good clinical outcome at 90 days.The levels of mRS were similar(P =0.490)between Solumbra and stent groups,but there was a tendency to higher rate of good clinical outcome at 90 days in Solumbra group (63.6％,7/11)than in stent group (47.6％,10/21).Conclusions Solumbra thrombectomy as intravascular revascularization technique is an effective and safe strategy for endovascular recanalization of acute large cerebral artery occlusion stroke.Compared with conventional Stent-Retriever thrombectomy,Solumbra thrombectomy has a good clinical outcome tendency at 90 days after operation.