Objective:To investigate the expression, regulation, potential mechanism and clinical significance of microRNA(miRNA)-129-1 in colon cancer.Methods:The changes of expression and methylation of miRNA-129-1 were analyzed from the methylation, mRNA expression and miRNA expression data of colon cancer in the cancer genome atlas (TCGA) database. The target genes of miRNA-129-1 were predicted from miRwalk 2.0 and TargetScan database. DAVID 6.7 online software was used for gene oncology and Kyoto encyclopedia of genes and genomes enrichment analysis. STRING database was used for protein-protein interaction analysis. TCGA data were applied again to analyze the differential expression and prognosis of key target genes of miRNA-129-1. Paired t test and independent sample t test were used for statistical analysis. The receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of miRNA-129-1 gene methylation in colon cancer. Kaplan-Meier method and log-rank test were used to analyze the effects of miRNA-129-1 expression on survival. Results:The sequence of miRNA-129-1 among different species was conserved. After all colon cancer samples, and control samples of TCGA database were analyzed, the results showed that compared with those of control samples, the expression of miRNA-129-1 decreased in cancer samples (0.98±0.81 vs. 5.74±0.59), and the methylation levels of cg04524088, cg04840800, cg11364290, cg20734982 and cg24044186 locus of miRNA-129-1 significantly decreased (0.321±0.130 vs. 0.563±0.051, 0.432±0.123 vs. 0.624±0.064, 0.475±0.153 vs. 0.768±0.033, 0.659±0.180 vs. 0.816±0.037 and 0.862±0.096 vs. 0.916±0.019, respectively) in colon cancer tissues, and the differences were all statistically significant ( t=14.95, 11.36, 9.39, 11.74, 5.32 and 3.47, all P<0.01). The results of ROC analysis showed that the methylation levels of the above five locus of miRNA-129-1 gene had high diagnostic efficiency in colon cancer (area under curve=0.946, 0.915, 0.950, 0.758 and 0.667, all P<0.01). The results of survival analysis indicated that low expression of miRNA-129-1 was associated with poor prognosis (hazard ratio ( HR)=0.55, P=0.018). The results of bioinformatics analysis demonstrated that the target genes of miRNA-129-1 were enriched in serine / threonine kinase receptor, mitogen-activated protein kinase and other functional gene clusters closely related to tumor, and there was a complex interaction network among the target genes proteins. The high expression of ephrin type-B receptor2 ( EPHB2) gene, a potential key target gene of miRNA-129-1, was associated with the short overall survival and disease-free survival time ( HR=1.9 and 1.6, both P<0.01). Conclusions:The expression and methylation of miRNA-129-1 play an important regulatory role in the development and development of colon cancer. The methylation of miRNA-129-1 has potential value in the diagnosis of colon cancer, and miRNA-129-1 is an influencing factor for the prognosis of patients with colon cancer. EPHB2 may be a potential key target gene of miRNA-129-1.

Objective To evaluate the role of circular RNA protein arginine methyltransferase 5 (circPRMT5) in the genesis and progression of colorectal cancer.Methods From January 2013 to December 2017,96 patients with colorectal cancer who underwent radical resection in Department of General Surgery,Jiading District Central Hospital Affiliated to Shanghai Medical College of Health were collected.The expression of circPRMT5 in colorectal cancer tissues was examined by real-time polymerase chain reaction (RT-PCR).The correlation between circPRMT5 expression level and age,gender,tumor size,tumor location,pathological differentiation,TNM stage,lymph node metastasis of patients with colorectal cancer was analyzed.The SW620 and LOVO cells were divided into control group,circPRMT5-lenti group and circPRMT5-shRNA-lenti group according to different interventions.The effects of circPRMT5 expression level on viability,apoptosis,mitochondrial membrane potential and migration of SW620 and LOVO cells were detected.The influence of circPRMT5 expression level on E-cadherin,Slug,N-cadherin and vimentin was determined by Western blotting method.The potential target miRNA of circPRMT5 was predicted by Starbase V2.0.Student's t test,analysis of variance and chi-square test were performed for statistical analysis.Results The results of RT-PCR showed that the expression of circPRMT5 in colorectal cancer tissues was higher than that of adjacent cancer tissues (2.167 ± 0.345 vs.1.103 ± 0.144),and the difference was statistically significant (t =26.847,P ＜ 0.01).The circPRMT5 expression level was positively correlated with tumor size,TNM stage,lymph node metastasis and distant metastasis (x2 =6.010,10.971,5.321 and 6.272,all P ＜0.05).The upregulation of circPRMT5 expression could promote proliferation and migration of SW620 and LOVO cells.The circPRMT5 downregulation could inhibit cell proliferation,induce apoptosis and decrease mitochondrial membrane potential.The results of Western blotting indicated that,compared with those of control group,the expression of Slug,N-cadherin and vimentin increased in circPRMT5-1enti group (1.023 ±0.038 vs.2.105 ±0.042,1.051 ±0.309 vs.2.277 ± 0.111,1.055 ± 0.040 vs.2.002 ± 0.537,respectively),however the expression of E-cadherin decreased (2.074 ± 0.214 vs.0.627 ± 0.023),and the differences were statistically significant (t =31.817,22.065,14.536 and 9.148,all P ＜ 0.01).Compared with the control group,the expression of Slug,N-cadherin and vimentin decreased in circPRMT5-shRNA-lenti group (1.023 ± 0.038 vs.0.585 ± 0.023,1.051 ± 0.309 vs.0.616 ± 0.043,1.055 ±0.040 vs.0.537 ±0.022),while the expression of E-cadherin increased (2.074 ± 0.214 vs.2.756 ± 0.148),and the differences were statistically significant (t =-13.795,-14.252,-11.794 and-13.116,all P ＜ 0.05).A total of 21 miRNAs might have potential binding sites with circPRMT5 predicted by Starbase V2.0 software.The expression of miRNA4735-3p,miRNA202-3p,miRNA326,let-7i-5p and miRNA4500 was negatively correlated with circPRMT5 expression in both SW620 and LOVO cells confirmed by RT-PCR.Conclusion CircPRM75 is an important oneogenic gene in the genesis and progress of colorectal cancer,and may have certain potential application prospect in the research and development for colorectal cancer.

Objective To explore the expression and clinical pathological significance of long non-coding transcription factor 7 (lncTCF7) in gastric cancer tissues and to investigate the role of lncTCF7 in the invasion and metastasis of gastric cancer by in vitro experimental study.Methods From January to June 2011,one hundred patients with gastric cancer who underwent radical gastrectomy were selected from Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine.The expression of lncTCF7 at mRNA level was detected by quantitative real-time polymerase chain reaction (qRT-PCR).The patients were divided into high expression group (50 cases) and low expression group (50 cases) according to the lncTCF7 mRNA expression level.The stable interferenced lncTCF7 cell line (stable interference group) and blank control lncTCF7 cell line (blank control group) were established.Then the relationship between lncTCF7 expression level and clinical pathological characteristics and prognosis was analyzed.The interferenced lncTCF7 cell line was constructed and utilized,and the role of lncTCF7 in the invasion and metastasis of gastric cancer was detected by wound healing,Transwell and Western blotting method.The Chi square test and t test were performed for statistical analysis.The Kaplan-Meier curve was used for survival analysis.Univariate and multivariate analyses were used for screening the independent factors affecting prognosis.Results The results of qRT-PCR showed that the expression levels of lncTCF7 mRNA in high expression group and low expression group were 0.019 ± 0.003 and 0.002 ± 0.001,respectively.The survival rate of high expression group was lower than that of low expression group (46％,23/50 vs.72％,36/50),and the difference was statistically significant (P =0.002 5).The expression level of lncTCF7 was correlated with intravascular tumor thrombus formation,nerve invasion,depth of invasion and lymph node metastasis (x2 =7.862,7.162,11.903 and 8.280,all P ＜ 0.05).The results of univariate and multivariate analyses showed that the expression level of lncTCF7 was significantly correlated with the depth of invasion (hazard ratio (HR) =4.205,P =0.002;HR =3.125,P =0.018).The results of wound healing assay indicated that lncTCF7 interference could significantly inhibit wound healing ((92.90 ± 1.51) ％ vs.(12.33 ± 0.67) ％,t =48.72,P ＜ 0.01).The results of Transwell assay demonstrated that after 24 hours of culture the number of cells passed through the membrane of the chamber of blank control group was higher than that of stable interference group (83.6 ± 12.5 vs.26.6 ± 4.3),and the difference was statistically significant (t =9.65,P ＜ 0.01).The results of Western blotting showed that the expression of E-cadherin,a marker of epithelial origin,of stable interference group was significantly increased compared with that of blank control group (0.32 ±0.01 vs.0.76 ± 0.01),however the expression levels of vimentin and N-cadherin,markers of mesenchymal origin,were significantly decreased (0.56 ±0.01 vs.0.39 ± 0.01 and 0.67 ± 0.01 vs.0.33 + 0.01),and the differences were all statistically significant (t =26.68,10.09 and 24.14,all P ＜ 0.05).Conclusions The prognosis of gastric cancer patients with high expression of lncTCF7 is poor.lncTCF7 may promote the invasion and metastasis of gastric cancer by influencing eoithelial-mesenchymal transition in gastric cancer cells.

Screening has been proven to be effective for the control of colorectal cancer (CRC).The target of CRC screening is shifting from CRC to colorectal neoplasia (CN),the precursors of CRC.Based on the the latest national guideline,the Consensus of Screening for CRC and CN,and the recent research of precursors both at home and abroad.This paper summarizes the progress in the research of risk factors,risk prediction model,screening strategy optimization,colonoscopy quality control,sessile serrated adenoma identification and follow up as well as the recognition of precursors.

Background: Mast cell activation is a characteristic of irritable bowel syndrome (IBS).Study on mast cell and the related inflammatory mediators in colonic mucosa is helpful for the evaluation and treatment of IBS.Aims: To assess the effect of mesalazine combined with trimebutine on colonic mucosal mast cell and related inflammatory mediators in patients with IBS.Methods: Forty patients with diarrhea-predominant IBS (IBS-D) and 40 patients with constipation-predominant IBS (IBS-C) from Oct.2014 to June 2016 at Shanghai Jiading District Central Hospital were enrolled, 20 healthy volunteers were served as controls.Forty patients with IBS-D and 40 patients with IBS-C were randomly divided into mesalazine+trimebutine group and trimebutine group, the treatment courses were all 4 weeks.Number of mast cell was counted by modified toluidine blue staining.Score of related inflammatory mediators were evaluated by immunohistochemistry.Clinical efficacy was assessed.Results: Compared with healthy controls, number of mast cell at baseline was significantly increased both in IBS-D and IBS-C patients (P<0.05).After treatment with mesalazine+trimebutine, number of mast cell was significantly decreased (P<0.05).At baseline, immunohistochemical staining score of 5-HT, IL-1, TNF-α, histamine, tryptase were significantly increased in IBS patients than in healthy controls (P<0.000 1).After treatment with mesalazine+trimebutine, above-mentioned inflammatory mediators were significantly decreased (P<0.05).In IBS-D patients, the total efficacy rate in mesalazine+trimebutine group was significantly increased than that in trimebutine group (85.0% vs.45.0%, P=0.008).In IBS-C patients, no significant difference in total efficacy rate was found between mesalazine+trimebutine group and trimebutine group (55.0% vs.25.0%, P=0.053).Conclusions: Mesalazine combined with trimebutine is an effective and safe approach to reduce mast cell infiltration and release of related inflammatory mediators, and is more efficient for patients with IBS-D.

Objective To explore the effect of trans-theoretical-model-based home visiting on hip function in community patients after hip joint replacement. Methods We chose 65 patients after hip joint replacement from January 2015 to March 2016 in our hospital:32 patients on odd days were set as the control group, where routine home visiting was done and the other 33 on even days as the experimental group, where community visiting based on trans-theoretical model. The two groups were compared in terms of Harris hip score at discharge and 6 months after discharge. Result The Harris hip score in the intervention group was significantly higher than that in the control group 6 months after discharge (P<0.05) and the hip function of the intervention group was better than that of the control group. Conclusions Community home visiting based on theoretical model can improve the hip function of patients after hip joint replacement compared with conventional health education models. This intervention method is worthy of popularization and application in community health education.

Objective To determine the population pharmacokinetics of intravenous etomidate infusion in adult patients.Methods Twenty-nine ASA Ⅰ or Ⅱ patients of both sexes aged 25-82 yr weighing 45-80 kg received contant-rate infusion of etomidate at 60 μg· kg-1 · min-1 until BIS value dropped to ≤ 40.Arterial blood samples were obtained from radial artery for determination of plasma etomidate concentration before,at 1,3,5 min of continuous etomidate infusion and at 1,3,5,7,10,20,30,45,75,120,180,240,300 and 360 min after termination of etomidate infusion.Population pharmacokinetic model was established by using the software package NONMEM.Population pharmacokinetic parameters were calculated according to etomidate concentrations and covariates including age,height,bodyweight,sex,liver-kidney function etc.using software package NONMEM.Results Pharmacokinetics of etomidate was best described by a three-compartment pharmacokinetic model with age as a covariate affecting systemic clearance (CL1).The typical parameters were:V1 =4.7 L,V2 =11 L,V3 =123L,CL1 =1.28-0.0119 × (Age (yr)-55) L/min,CL2 =1.25 L/min and CL3 =1.08 L/min respectively.Context-sensitive half-time increased with age and steady-state infusion time.Conclusion Pharmacokinetics of etomidate is best described by a three-compartment pharmacokinetic model with age as a covariate affecting systemic clearance (CL1).

ObjectiveTo investigate the effect and underling mechanism of water-soluble CO-releasing molecules (CORM-3)on the alleviation of allograft rejectionafter mouse kidney transplantation.Methods A mice kidney transplantation model was established using C.FVB-Tg (Itgax-DTR/GFP)57Lan/J or C57BL/6J (H-2Kb) mice as donors,and Balb/c (H-2Kd) mice as recipients.After donor nephrectomy,kidney was preserved in UW solution which contained CORM-3 or iCORM (inactive CO-releasing molecules) for 24 h in 4℃.Recipient survival after removal of both na? ve kidneys,serum creatinine as well as graft histology was observed.In the C.FVB-Tg(ItgaxDTR/GFP) 57Lan/J donors,rDCs were acquired in vitro and selected by magnetic cell sorting (MACS) after graft nephrectomy.The expression of activation markers,CD80 and CD86,on rDC was assessed by using flow cytometry.ResultsThe graft medium survival time was 40.5 days in the iCORM group and 70 days in the CORM-3 group respectively (P＜0.05).CORM-3 preserved the graft function as shown by significantly lower serum creatinine (P＜0.05; or P＜0.01) and alleviated graft pathology injury.Diffuse infiltration of mononuclear cells in the interstitial tissues,moderate tubulitis and partial glomerular sclerosis were found in the iCORM graft kidney,while the CORM-3 graft kidney displayed almost normal histology.Meanwhile,CORM-3 suppressed the expression of CD80 and CD86 in donor-derived rDC.ConclusionCORM-3 can alleviate allograft rejection,prolong the graft survival,and improve kidney function in mouse kidney transplantation,probably via inhibiting rDC activation.

ObjectiveTo investigate the role of aldehyde dehydrogenase 2 (ALDH2) in the protection against tubular epithelial cells (TEC) ischemia/reperfusion (IR)injury induced by pretreatment with ethanol.Methods Mouse primary cultured TECs were pretreated with 50 mM ethanol 3 h before simulation of in vitro IR.Lactate dehydrogenase (LDH) release was assessed to evaluate the protection of ethanol pretreatment on IR injury.Thereafter,TECs were transfected with a negative control siRNA (NC) or an ALDH2-siRNA. The ALDH2 protein levels and ALDH enzymatic activities were assessed 48 h after transfection.Ethanol pretreatment and in vitro IR were performed on those transfected TECs.LDH release was assessed to evaluate the role of ALDH2 in the ethanol pretreatment-induced protection against IR injury.ResultsEthanol pretreatment significantly reduced the LDH release in TECs upon IR insult.As compared with NC group and INTERFERin group,the ALDH2 protein levels were decreased by 82.1％,ALDH enzymatic activities were decreased hy 67.3％,and the protective effect induced by ethanol pretreatment was almost completely abrogated in ALDH2-siRNA group.ConclusionEthanol pretreatment protects TECs against IR injury through ALDH2 dependent pathways.