Problem-based learning has gradually become an important pedagogical tool in the medical curriculum.Behaviors of PBL tutor play an unique role in teaching.A good PBL tutor must consider the following issues:ample preparing before class,awareness of learning outside the tutorial room,social congruence,dealing with the difficult student and dysfunctional group,sharing the PBL experience and seeking support or advice from peers.

Histone methylation is one of the epigenetic modifications. Histone methylation influences constitutive heterochromatin, genomic imprinting, inactivation of X-chromosome and gene transcription regulation. Abnormality of histone methylation is associated with several carcinomas. The discovery of enzymes that reverse histone methylation challenges the current understanding that histone methylation is a stable epigenetic marker and provides a novel way to study histone modifications.

Most colorectal cancers develop from adenomas. Environmental factors play an important role in the development and progression of adenoma. Recently,epidemiologic investigations on lifestyle change including diet and exercise and drug intervention studies have proved the relationship between environmental factors and colorectal cancer. Screening,polypectomy and surveillance via colonoscopy are the main measures of colorectal cancer prevention. However, the efficacy is unsatisfactory. Therefore,attention should be paid to studies on colorectal cancer prophylaxis via intervention on environmental factors. Emphasis should be put on various aspects of environmental intervention in clinical practice,and prophylaxis strategies should be generated individually in accordance with the local condition and situation.

Colorectal cancer(CRC) is one of the most common tumors with a high prevalence of cancer-related morbidity and mortality.Several environmental factors,especially dietary factors,can affect the initiation and development of CRC.Recent studies have shown that adjusting nutrition components in diet,such as folate,calcium,vitamin D,selenium and fibre,may help to prevent the development of CRC.The objective of article is to review mechanisms of these nutritional components in the process of preventing CRC.

Objective To evaluate the efficacy and safety of compound azintamide enteric-coated tablet in the treatment of patients with post-cholecystectomy dyspepsia.Methods A multicentre,randomized,double-blinded,placebo-controlled trail was conducted.A total of 120 patients with post-cholecystectomy dyspepsia were divided into azintamide group (n=60) and placebo group (n＝60),taking compound azintamide enteric-coated tablet or placebo 100 mg each time,three times per day for 28 days.The score of each dyspeptic symptom (abdominal distension,loss of appetite,early satiety,belching,nausea,abdominal pain or abdominal discomfort) and total score of dyspepsia were evaluated prior to study and on the 7th,14th,21st and 28th day after treatment.The efficacy of the improvement of dyspeptic symptoms was compared between the two groups on the 28th day after treatment and the safety was evaluated.The score of the quality-of-life was compared between the two groups prior to study and on the 28th day after treatment.The t-test or chi-square test was performed for statistical analysis.Results The scores of abdominal distension,belching,nausea,abdominal pain or abdominal discomfort and the total score of azintamide group on the 7th day after treatment (5.7±3.1,3.5±2.1,0.3±0.1,3.3±1.7 and 17.9±9.6) were significantly lower than those prior to study (8.9±5.3,5.3±2.5,0.9±0.4,4.5±3.7,24.3±14.5;t=3.758,3.976,10.494,2.125 and 2.654,allP＜0.05).On the14th,21st and28thday after treatment in azintamide group,the score of each dyspeptic symptom and the total score were lower than those prior to study.The symptom of abdominal distension significantly improved on the 7th,14th,21st and 28th day after treatment in placebo group,and the score of early satiety and total score of dyspepsia were significantly lower on the 28th day after treatment compared with those before treatment.In azintamide group,the total efficacy rate was 66.7％ (40/60),which was higher than that of placebo group (38.3％,23/60) and the difference was statistically significant (x2 =9.653,P ＜ 0.01).On the 28th day after treatment,SF-NDI of azintamide group was 4.4±3.4,which was significantly lower than that of placebo group (9.6±6.0) and the difference was statistically significant (t=5.450,P＜0.01).In azintamide group there was one patient with rash on the 7th day after treatment,and in placebo group there was one patient with headache on the 14th day after treatment.The symptoms disappeared seven days after medicine withdrawal.Conclusion Compound azintamide enteric-coated tablet effectively improves dyspeptic symptoms and quality of life in patients with post-cholecysteetomy dyspepsia and has good safety.

Objective To investigate whether EZH2 participates in the process of authphagy and its regulatory mechanism in CRC (colorectal cancer) .Methods ZEB1 ,EZH2 and PTEN expression were measured by Western blot and immunohistochemistry respectively .ZEB1 ,EZH2 and PTEN mRNA level were measured by real-time PCR .Electron microscopy was introduced to validate the existence of autophagy .Results Knockdown of EZH2 induced the formation of autophagosome in colorectal cancer cell lines , which was evident on electron microscopy .Furthermore ,Western Blot and real-time PCR data showed that ZEB1 and EZH2 may regulate the expression of PTEN ,which played a vital role in autophagy .Moreover ,downregulation of ZEB1 significantly reduced the expression of EZH2 .An inverse correlation between the expression of EZH2 and ZEB1 ,and the expression of PTEN was also revealed in CRC tissues ,when compared with normal tissue in patients .Conclusion The impact of EZH2 on autophagy via PTEN during CRC carcinogenesis is revealed .At the same time ,EZH2 expression may be regulated by ZEB1 in colorectal cancer .

Colorectal cancer remains a major threat to people’s health around the world. Researchers have paid more and more attention to colorectal cancer epigenetics. From two main aspects of colorectal cancer epigenetics: DNA methylation and histone modiifcation, this article analyzes the similarities and differences between patients with colorectal cancer in Eastern and Western countries. This review brielfy introduces epigenetic modiifcation of genes that were used to be biomarkers and therapeutic targets. Although there are some common features of colorectal cancer in the world, analysis has showed that some obvious epigenetic differences do exist in different races. For example, it had been conifrmed in the studies that there are differences in speciifc gene methylation, histone modiifcation sites and the degree of methylation and acetylation among countries, which provide the basis for speciifc diagnosis, treatment and prognosis of colorectal cancer in different ethnic groups. With improved research methods and increased sample size, more and more special molecular targets of colorectal cancer tissues will be found, and then personalized therapy for colorectal cancer can be achieved.

Objective To explore the efficacy and safety of compound azintamide enteric‐coated tablets in the treatment of patients with dyspepsia after gastrointestinal surgery .Methods Multicenter , randomized ,double blind ,placebo‐controlled ,parallel controlled method w as applied .From January 2011 to January 2013 , of 240 patients with dyspepsia after gastrointestinal surgery from 12 hospitals in Shanghai were enrolled and divided into medicine treatment group (n= 120) and placebo control group (n= 120 ) ,received compound azintamide enteric‐coated tablets or placebo , respectively . Compound azintamide enteric‐coated tablet (100 mg) or placebo was oral taken each time ,three times per day for four weeks .Total and respective score of dyspeptic symptoms (abdominal distension ,loss of appetite ,early satiety ,belching ,nausea ,abdominal pain or abdominal discomfort) were evaluated prior to study and on the 1st , 2nd , 3rd and 4th week after treatment . On the 4th week after treatment ,the efficacy of the improvement of dyspeptic symptoms was compared between the two groups ,and the safety was also evaluated .The score of the quality‐of‐life was compared between the two groups prior to study and on the 4thweek after treatment .The t‐test was performed for comparison between measurement data ,Chi‐square test was used for count data ,and rank sum test was used for rank data .Results At one week after treatment ,the scores of abdominal distension (4 .61 ± 0 .98 ) ,early satiety (2 .87 ± 0 .64 ) ,belching (3 .03 ± 0 .58) ,abdominal pain or abdominal discomfort (3 .13 ± 0 .79) and total score (18 .32 ± 3 .44) of patients in medicine treatment group were significantly lower than those of placebo control group (8 .83 ± 1 .28、4 .28 ± 0 .61、4 .87 ± 1 .07、5 .46 ± 0 .87、29 .63 ± 5 .50) ,and the differences were statistically significant (t=28 .524、17 .400、16 .453、21 .619 and 18 .983 ,all P< 0 .01 ) . However there was no significant difference in the scores of loss of appetite and nausea (both P> 0 .05) .At 2nd ,3rd and 4th week after treatment ,respective score of dyspeptic symptoms and total score of medicine treatment group (2nd week:2.57±1.28,1.87±1.17,1.55±1.27,1.55±1.08,1.09±0.82,1.98±1.02,10.53±4.54,3rdweek:1 .42 ± 0 .60 ,1 .11 ± 0 .45 ,0 .94 ± 0 .37 ,0 .94 ± 0 .41 ,0 .79 ± 0 .31 ,1 .42 ± 0 .55 ,6 .52 ± 2 .41 ,4th w eek:1.13±0.51,0.46±0.12,0.58±0.13,0.38±0.16,0.30±0.07,0.81±0.33,3.65±1.06)wereall significantly lower than those of placebo control group (2nd week:8 .50 ± 2 .61 ,3 .78 ± 2 .01 ,4 .08 ± 2 .14 , 4.73±2.64,2.27±2.13,4.91±2.24,28.25±8.86,3rdweek:7.92±2.51,3.68±1.76,4.08±1.86, 4.71±1.77,2.14±0.83,5.01±1.31,27.54±8.09,4th week:7.63±2.37,3.67±1.63,3.92±2.08, 4 .66 ± 2 .95 ,2 .14 ± 1 .65 ,4 .67 ± 2 .34 ,and 26 .68 ± 7 .45) ,and the differences were statistically significant (all t=0 .000 ,all P<0 .01) .At 4th week after treatment ,the total efficacy of total score improvement of dyspepsia symptoms in medicine treatment group was 86 .21% (100/116) ,which was significantly better than that of placebo control group (39 .16% (47/120)) ,and the difference was statistically significant (Z=9 .464 ,P<0 .01) .The total score of quality of life in medicine treatment group was significantly lower than that of placebo control group (12 .24 ± 4 .30 and 22 .13 ± 6 .18) ,and the difference was statistically significant (t=14 .225 , P< 0 .01 ) .No adverse events was observed in both groups during treatment period . Conclusion Compound azintamide enteric‐coated tablets may effectively improve dyspeptic symptoms and quality of life in patients with dyspepsia after gastrointestinal surgery ,and with good safety .

Objective To investigate the relationship of the expression of DNA methyltransferase,demethylase(mbd2) and tumor-associated genes in human gastric cancer. Methods Tissue samples of cancerous,para-cancerous and normal gastric mucosa were obtained surgically from 28 primary gastric cancer patients. The transcription level of DNA methyltransferase 1 (DNMT1),mbd2,methyl-CpG binding protein (MeCP2),p16 INK4A and c-myc were determined by using real-time RT-PCR and RT-PCR. The relationship between the expression of DNA methylation-associated genes and tumor-associated genes was analyzed. Results The mRNA level of DNMT1 was higher and the mRNA level of mbd2 gene was lower in cancerous tissue than that in normal tissue. The expression of c-myc instead of p16 INK4A and MeCP2 was increased in cancer tissues. The mRNA level of c-myc related negatively to mbd2 when gastric cancer developed. However,there was no any close relation between the transcription level of all above genes and tumor biological behavior in human gastric cancer. Conclusion This study indicates that MeCP2 but not DNMT1 may contribute to the regulation of tumor-associated genes expression in human gastric cancer.

Objective To study the effects of extracellular-signal regulated kinase mitogenactivated protein kinase (ERK-MAPK) signaling pathway inhibition on histone phosphorylation and the related gene expression in human colorectal cancer cells.Methods Two human colorectal cancer cell lines (SW1116 and HCT116) were cultured and treated with gradient(0,20,40/μmol/L) doses of ERK-MAPK signaling pathway inhibitor U0126.Cell viability was determined by cell counting kit 8 (CCK-8) assay.Cell cycle distribution was assessed by flow cytometry.The expression levels of histone H3 kinases including ribosomal S6 serine-threonine kinase (RSK-2) and mitogen-and stressactivated protein kinase 1 and 2 (MSK1 and MSK2),and the levels of histone H3 (Ser10) phosphorylation and c-Fos protein were detected using Western blotting.Results Treatment of these two human colorectal cancer cell lines with ERK-MAPK inhibitor resulted in a time and dose-dependent inhibition of cell proliferation significantly. Proliferation rate of HCT116 was reduced to 47% at 72 hours after 40/μmol/L U0126 treatment. Cell cycle analysis showed that the percentage of phase G0/G1 cells significantly increased (P<0. 01) and the percentage of phase S cells decreased (P<0.01) after treatment with ERK-MAPK inhibitor. The expression of MSK1 and RSK2 reduced obviously in both of human colorectal cancer cell lines treated with U0126, which resulted in a 28% and 40% reduction of levels of MSK1 and RSK2 as compared with control HCT116 cells respectively,while no detectable change in the expression of MSK2 was found. Consistent with this, the expression level of histone H3 (ser10) phosphorylation was markedly down-regulated by ERK-MAPK inhibitor, and the related protein c-Fos expression decreased accordantly. Conclusions Decreased ERK-MAPK signaling pathway may reduce histone H3 (Ser10) phosphorylation via suppression of the activity of histone H3 kinase including MSK1 and RSK2, but not MSK2, consequently decrease the expression of c-Fos protein, which results in the inhibition of colorectal cancer cells proliferation.