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Pancreatic neuroendocrine tumor (pNET) is a heterogeneous group of neoplasms that vary in their clinical presentation, biological behavior and prognosis. The most common site of metastasis is the liver. Surgical resection of both primary tumor and liver metastases is thought to have the best long-term outcomes by achieving a radical resection. The role of primary tumor resection in the setting of unresectable metastatic disease is controversial; However, more and more studies demonstrate an active cytoreductive surgery will benefit patients with a reasonable preoperative evaluation. For patients who are not surgical candidates, neoadjuvant therapy is attempted to find if it would downstage the tumor to regain the opportunity of R0 resection. Cytotoxic chemotherapy, targeted therapy, and PRRT present good treatment prospects, and further research is still needed. With multidisciplinary treatment, individualized protocol should provide patients a better treatment results.
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Objective:To construct a prognosis associated micro RNA(miRNA) prediction model based on bioinformatics analysis and evaluate its application value in pancreatic cancer patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 171 pancreatic cancer patients from the Cancer Genome Atlas (TCGA) (https: //cancergenome.nih.gov/) between establishment of database and September 2017 were collected. There were 93 males and 78 females, aged from 35 to 88 years, with a median age of 65 years. Of the 171 patients, 64 had complete clinicopathological data. Patients were allocated into training dataset consisting of 123 patients and validation dataset consisting of 48 patients using the random sampling method, with a ratio of 7∶3. The training dataset was used to construct a prediction model, and the validation dataset was used to evaluate performance of the prediction model. Nine pairs of miRNA sequencing data (GSE41372) of pancreatic cancer and adjacent tissues were downloaded from Gene Expression Omnibus database. The candidate miRNAs were selected from differentially expressed miRNAs in pancreatic cancer and adjacent tissues for LASSO-COX regression analysis based on the patients of training dataset. A prognosis associated miRNA prediction model was constructed upon survival associated miRNAs which were selected from candidate differentially expressed miRNAs. The performance of prognosis associated miRNA prediction model was validated in training dataset and validation dataset, the accuracy of model was evaluated using the area under curve (AUC) of the receiver operating characteristic curves and the efficiency was evaluated using the consistency index (C-index). Observation indicarors: (1) survival of patients; (2) screening results of differentially expressed miRNAs; (3) construction of prognosis associated miRNA model; (4) validation of prognosis associated miRNA model; (5) comparison of clinicopathological factors in pancreatic cancer patients; (6) analysis of factors for prognosis of pancreatic cancer patients; (7) comparison of prediction performance between prognosis associated miRNA model and the eighth edition TNM staging. Measurement data with normal distribution were represented as Mean± SD, comparison between groups was analyzed by the student- t test, and comparison between multiple groups was analyzed by the AVONA. Measurement data with skewed data were represented as M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Ordinal data were analyzed using the rank sum test. Correlation analysis was conducted based on count data to mine the correlation between prognosis associated miRNA model and clinicopathological factors. COX univariate analysis and multivariate analysis were applied to evaluate correlation with the results described as hazard ratio ( HR) and 95% confidence interval ( CI). HR<1 indicated the factor as a protective factor, HR>1 indicated the factor as a risk factor, and HR equal to 1 indicated no influence on survival. The Kaplan-Meier method was used to draw survival curve and calculate survival rates, and the Log-rank test was used for survival analysis. Results:(1) Survival of patients: 123 patients in the training dataset were followed up for 31-2 141 days, with a median follow-up time of 449 days. The 3- and 5-year survival rates were 16.67% and 8.06%. Forty-eight patients in the validation dataset were followed up for 41-2 182 days, with a median follow-up time of 457 days. The 3- and 5-year survival rates were 15.63% and 9.68%. There was no significant difference in the 3- or 5-year survival rates between the two groups ( χ2=0.017, 0.068, P>0.05). (2) Screening results of differentially expressed miRNAs. Results of bioinformatics analysis showed that 102 candidate differentially expressed miRNAs were selected, of which 63 were up-regulated in tumor tissues while 39 were down-regulated. (3) Construction of prognosis associated miRNA model: of the 102 candidate differentially expressed miRNAs, 5 survival associated miRNAs were selected, including miR-21, miR-125a-5p, miR-744, miR-374b, miR-664. The differential expression patterns of pancreatic cancer to adjacent tissues were up-regulation, up-regulation, down-regulation, up-regulation, and down-regulation, respectively, with the fold change of 4.00, 3.43, 3.85, 2.62, and 2.35. A prognostic expression equation constructed based on 5 survival associated miRNAs = 0.454×miR-21 expression level-0.492×miR-125a-5p expression level-0.49×miR-744 expression level-0.419×miR-374b expression level-0.036×miR-664 expression level. (4) Validation of prognosis associated miRNA model: The C-index of prognosis associated miRNA model was 0.643 and 0.642 for the training dataset and validation dataset, respectively. (5) Comparison of clinicopathological factors in pancreatic cancer patients: results of COX analysis showed that the prognosis associated miRNA model was highly related with pathological T stage and location of pancreatic cancer ( Z=45.481, χ2=10.176, P<0.05). (6) Analysis of factors for prognosis of pancreatic cancer patients: results of univariate analysis showed that pathological N stage, radiotherapy, molecular targeted therapy, score of prognosis associated miRNA model were related factors for prognosis pf pancreatic cancer patients ( HR=2.471, 0.290, 0.172, 2.001, 95% CI: 1.012-6.032, 0.101-0.833, 0.082-0.364, 1.371-2.922, P<0.05). Results of multivariate analysis showed that molecular targeted therapy was an independent protective factor for prognosis of pancreatic cancer patients ( HR=0.261, 95% CI: 0.116-0.588, P<0.05) and score of prognosis associated miRNA model≥1.16 was an independent risk factor for prognosis of pancreatic cancer patients ( HR=1.608, 95% CI: 1.091-2.369, P<0.05). (7) Comparison of prediction performance between prognosis associated miRNA model and the eighth edition TNM staging: in the training dataset, there was a significant difference in the prediction probability for 3- and 5-year survival of pancreatic cancer patients between prognosis associated miRNA model and the eighth edition TNM staging ( Z=-1.671, -1.867, P<0.05). The AUC of the prognosis associated miRNA model and the eight edition TNM staging for 3- and 5-year survival prediction was 0.797, 0.935 and 0.737 , 0.703, with the 95% CI of 0.622-0.972, 0.828-1.042 and 0.571-0.904 , 0.456-0.951. The C-index was 0.643 and 0.534. In the validation dataset, there was a significant difference in the prediction probability for 3- and 5-year survival of pancreatic cancer patients between prognosis associated miRNA model and the eighth edition TNM staging ( Z=-1.729, -1.923, P<0.05). The AUC of the prognosis associated miRNA model and the eight edition TNM staging was 0.750, 0.873 and 0.721 , 0.703, with the 95% CI of 0.553-0.948, 0.720-1.025 and 0.553-0.889, 0.456-0.950, respectively. The C-index was 0.642 and 0.544. Conclusions:A prognosis associated miRNA prediction model can be constructed based on 5 survival associated miRNAs in pancreatic cancer patients, as a complementation to current TNM staging and other clinicopathological parameters, which provides individual and accurate prediction of survival for reference in the clinical treatment.
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Objective To investigate the risk factors of postoperative pancreatic fistula after pancreaticoduodenectomy (PD).Methods The retrospective case-control study was adopted.The clinicopathological data of 196 patients with PD who were admitted to First Affiliated Hospital of Dalian Medical University from September 2014 to July 2016 were collected.All the patients underwent PD.Observation indicators:(1) intra-and postoperative situations;(2) follow-up;(3) analysis of risk factors of pancreatic fistula after PD.All patients were followed up by outpatient examination and telephone interview to detect pancreatic fistula and peritoneal fluid collection up to March 2017.Measurement data with normal distribution were represented as (x)±s and comparison between groups was analyzed by t test.Measurement data with skewed distribution were represented as median (range).Count data and univariate analysis were done using the chi-square test.Logistic regression model was used for multivariate analysis.Results (1) Intra-and post-operative situations:all the 196 patients underwent surgeries successfully.The operation time,volume of intraoperative blood loss,number of intraoperative blood transfusion and non intraoperative blood transfusion were (439± 136) minutes,(686±280) mL,45 and 151 cases,respectively.Time to initial anal exsufflation,time of initial defecation and time for first diet after operation were (4.1 ±2.1) days,(5.1± 2.9) days and (3.1 ± 2.0) days.Of 76 patients,the content of diastase in the i ntraperitoneal drainage was 614 U/L (31-30 215 U/L) at postoperative day 1 and level of serum procalciton in was (0.7±0.4) ng/mL at postoperative day 3.Time for drainage tube removal of 196 patients was (14.6±7.1)days.Fifty four of 196 patients with postoperative complications were improved by symptomatic treatment,including 15 with intestinal obstruction,12 with delayed gastric emptying,11 with abdominal infection,9 with incision infection,7 with bleeding.Duration of postoperative hospital stay was (17.1 ±4.2)days.Results of pathological diagnosis of 196 patients showed 121 cases of pancreatic cancer,50 of intraductal papillary mucinous tumors of the pancreas,7ampullary carcinoma,15 of carcinoma of the lower end of the bile duct,and 3 of duodenum cancer.Pancreatic findings:pancreatic texture:95 cases were with soft pancreas and 101 with hard pancreas.Diameter of main pancreatic duct duct:101 cases had diameter of pancreatic duct duct ≥3 mm and 95 cases ＜3 mm.(2)Followup:all the 196 patients were followed up for 4-30 months,with a median follow-up time of 18 months.During follow-up time,the grade B/or C pancreatic fistula occurred in 37 cases.Of 16 patients with pancreatic fistularalated ascites,10 had readmission and were improved by symptomatic treatment.(3) Analysis of risk factors of pancreatic fistula after PD:the results of univariate analysis showed that the content of diastase in the intraperitoneal drainage at postoperative day 1,level of serum procalcitonin at postoperative day 3 and pancreatic texture were related factors affecting the pancreatic fistula after PD (x2 =6.569,5.902,13.517,P＜0.05).The results of multivariate analysis showed that the content of diastase in the intraperitoneal drainage at postoperative day 1 ≥600 U/L was an independent risk factor affecting the pancreatic fistula after PD (OR =9.135,95％confidence interval:2.247-37.130,P＜0.05).Conclusion The content of diastase in the intraperitoneal drainage at postoperative day 1 ≥ 600 U/L is an independent risk factor affecting the pancreatic fistula after PD.
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Objective To investigate the risk factors of postoperative pancreatic fistula after pancreaticoduodenectomy (PD).Methods The retrospective case-control study was adopted.The clinicopathological data of 196 patients with PD who were admitted to First Affiliated Hospital of Dalian Medical University from September 2014 to July 2016 were collected.All the patients underwent PD.Observation indicators:(1) intra-and postoperative situations;(2) follow-up;(3) analysis of risk factors of pancreatic fistula after PD.All patients were followed up by outpatient examination and telephone interview to detect pancreatic fistula and peritoneal fluid collection up to March 2017.Measurement data with normal distribution were represented as (x)±s and comparison between groups was analyzed by t test.Measurement data with skewed distribution were represented as median (range).Count data and univariate analysis were done using the chi-square test.Logistic regression model was used for multivariate analysis.Results (1) Intra-and post-operative situations:all the 196 patients underwent surgeries successfully.The operation time,volume of intraoperative blood loss,number of intraoperative blood transfusion and non intraoperative blood transfusion were (439± 136) minutes,(686±280) mL,45 and 151 cases,respectively.Time to initial anal exsufflation,time of initial defecation and time for first diet after operation were (4.1 ±2.1) days,(5.1± 2.9) days and (3.1 ± 2.0) days.Of 76 patients,the content of diastase in the i ntraperitoneal drainage was 614 U/L (31-30 215 U/L) at postoperative day 1 and level of serum procalciton in was (0.7±0.4) ng/mL at postoperative day 3.Time for drainage tube removal of 196 patients was (14.6±7.1)days.Fifty four of 196 patients with postoperative complications were improved by symptomatic treatment,including 15 with intestinal obstruction,12 with delayed gastric emptying,11 with abdominal infection,9 with incision infection,7 with bleeding.Duration of postoperative hospital stay was (17.1 ±4.2)days.Results of pathological diagnosis of 196 patients showed 121 cases of pancreatic cancer,50 of intraductal papillary mucinous tumors of the pancreas,7ampullary carcinoma,15 of carcinoma of the lower end of the bile duct,and 3 of duodenum cancer.Pancreatic findings:pancreatic texture:95 cases were with soft pancreas and 101 with hard pancreas.Diameter of main pancreatic duct duct:101 cases had diameter of pancreatic duct duct ≥3 mm and 95 cases ＜3 mm.(2)Followup:all the 196 patients were followed up for 4-30 months,with a median follow-up time of 18 months.During follow-up time,the grade B/or C pancreatic fistula occurred in 37 cases.Of 16 patients with pancreatic fistularalated ascites,10 had readmission and were improved by symptomatic treatment.(3) Analysis of risk factors of pancreatic fistula after PD:the results of univariate analysis showed that the content of diastase in the intraperitoneal drainage at postoperative day 1,level of serum procalcitonin at postoperative day 3 and pancreatic texture were related factors affecting the pancreatic fistula after PD (x2 =6.569,5.902,13.517,P＜0.05).The results of multivariate analysis showed that the content of diastase in the intraperitoneal drainage at postoperative day 1 ≥600 U/L was an independent risk factor affecting the pancreatic fistula after PD (OR =9.135,95％confidence interval:2.247-37.130,P＜0.05).Conclusion The content of diastase in the intraperitoneal drainage at postoperative day 1 ≥ 600 U/L is an independent risk factor affecting the pancreatic fistula after PD.
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Objective To investigate the impact of down-regulation of histone methyltransferase enhancer of zeste homolog 2 (EZH2) on RUNX3 expressions,proliferation and apoptosis in human pancreatic cancer.Methods The expressions of EZH2 and RUNX3 in 38 pancreatic cancer patients and human pancreatic cancer AsPC-1,PANC-1 and BxPC-3 cells were detected by immunohistochemistry and western blot,respectively.Cells were transfected with siEZH2 by lipofectamin 2000.Real time-PCR and western blot were used to detect EZH2 and RUNX3 expressions.Cell growth and apoptosis in vitro and vivo were assessed by MTT,flow cytometry and nude mice experiments,respectively.The correlation among the expressions of EZH2,clinical pathological features and overall survival rate were analyzed.Results Elevated EZH2 and decreased RUNX3 expressions were observed in human pancreatic cancer tissues and cells (P ＜ 0.05).Knockdown of EZH2 reduced cell growth and induced apoptosis in vitro and vivo by upregulating RUNX3 protein expression (P ＜ 0.05).In addition,the EZH2 expressions were correlated with tumor stage,lymph node metastasis and poor prognosis (P ＜ 0.05).Conclusions EZH2 expressions were correlated with malignancy and poor prognosis in pancreatic cancer.Tumor cell proliferation was promoted by EZH2 through down-regulation of RUNX3.EZH2 may be a potential therapeutic target for pancreatic cancer.
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Objective:To establish an HPLC method for the determination of content and entrapment efficiency of HIV-1 virus in-fection factor Vif inhibitor VEC-5 liposomes. Methods:VEC-5 liposomes were prepared by a method of freeze-drying and reconstruc-tion. The separation of free drug from the liposomes was achieved by ultracentrifugation, and an HPLC method was used to determine the content and entrapment efficiency of VEC-5 liposomes. Results:The linear range of VEC-5 was 20-100 μg·ml-1(r=0. 999 0). The average recovery was 100. 25% and RSD was 0. 93%(n=9). The content of three batches of VEC-5 liposomes was 98. 63%, 100. 43% and 102. 65%, respectively within the range of 90%-110%, and the entrapment efficiency was 94. 89%, 93. 68% and 94. 56%, respectively, which was above 90%. Conclusion:The method is accurate and reliable, which can be used to determine the content and entrapment efficiency of VEC-5 liposomes.
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Objective To analyze the common causes leading to lung infection following renal transplantation and provide targeted preventive measures to reduce the incidence of lung infection.Methods The clinical data of 561 recipients who underwent renal transplantation from January 2006 to February 2011 were retrospectively analyzed.The recipients were divided into two groups:group Ⅰ,from January 2006 to December 2009 (n =416) ; group Ⅱ,from January 2010 to February 2011 (n =145).The causes possibly leading to lung infection which took place 3 days before the appearance of the clinical symptoms were offered by the patients who suffered lung infection of group Ⅰ.And then the causes were summarized and analyzed to formulate the specific and comprehensive measures to prevent the infection.Finally the measures were applied to recipients in group Ⅱ from January 2010.After applying the measures for 14 months,the incidence of lung infection in group Ⅱ was counted and compared with that in group Ⅰ to see the preventive effect.Results There were 58 cases of lung infection in group Ⅰ (58/416,13.9％) and 12 cases in group Ⅱ (12/145,8.3％). There was significant difference in the incidence of lung infection between two groups (x2 =4.0361,P＜0.05).All of the recipients with lung infection were hospitalized in six months after the transplantation.The causes leading to lung infection of 58 cases in group Ⅰ were as follows:6 cases due to being excessively tired,3 cases due to guest visiting,12 cases due to abrupt change of weather,9 cases due to exposure to public place,8 cases due to returning to hospital,6 cases due to close contact with children,5 cases due to close contact with animals,and the other 9 cases without specific causes found.Conclusion The incidence of lung infection following renal transplantation can be notably reduced by the application of targeted and concrete health propaganda education and preventive measures based on analysis on the specific causes of infection.
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We developed a high-sensitivity C-reactive protein quantifiable chemiluminescent immunoassay (hs-CRP CLIA). The high-purity native CRP was purified from hepatic cirrhosis patient ascetic fluid by affinity and ion exchange chromatography and used as an immunogen to develop the monoclonal antibodies (mAbs) against CRP. Twenty-two mAbs were identified reactive with CRP in ELISA and 13 of them were reactive in the phosphorycholine ligand capture ELISA. The mAbs 10C5 and 10C11 were selected to develop the hs-CRP CLIA. The linearity and performance of the hs-CRP CLIA was characterized. It was showed not reactive when testing against other serum materials (IgG, hemoglobin and triglyceride). The reliable correlation (R2 > 0.993) was obtained between testing value (RLU/S) and the concentration of human serum CRP calibrator. The linearity fell in the range of 0.04-20.38 mg/L. The assay has good accuracy and reproducibility, the mean recovery was 99% and the precision of the intra- and inter assay was CVs (4.2%-5.8%) and (9.0%-11.5%), respectively. In testing of 90 human sera, this assay performed well and correlated comparably with a commercial hs-CRP ELISA kit. Thus, hs-CRP CLIA is an accurate, reliable, quantifiable assay for detection of high-sensitive C-reactive protein in serum, it may be useful to improve the risk assessment of cardiovascular disease and the prognosis of inflammatory bowel disease.
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Humans , C-Reactive Protein , Chemistry , Immunoassay , Methods , Luminescent Measurements , Methods , Sensitivity and SpecificityABSTRACT
Objective To evaluate the effects of endothelial nitric oxide synthase (eNOS) gene transfer on intrahepatic vascular resistance (IHVR) and portal venous pressure (PVP) in cirrhotic rats. Methods (1) 5 days after eNOS gene transfer, the in situ liver perfusion system (ISLP) was prepared and in different groups of controls and eNOS treated rats, the followings were analyzed: portal perfusion pressure (PP) dose-response curve to norepinephrine (NE); the effects on PP caused by specific nitric oxide synthase (NOS) inhibitor N-monomethyl-L- arginine (L-NMMA) or the nitric oxide (NO) synthesis substrate L-arginine (L-Arg). (2) The experiment of perfusion via portal vein in vivo was performed and the effects of L-NMMA on the PVP was observed. Results (1) In ISLP model, after L-NMMA was added into the perfusate of the control rats, PP dose-respose to NE increased remarkably and the peak of PP increased to (26.7?0.9) mm?Hg. The increased PP response to NE caused by L-NMMA was offsetted by L-Arg and the peak of PP decreased to (23.2?0.9) mm?Hg. In eNOS treated rats, PP response to NE was significantly lower than that in controls (P