This paper analyzed the necessity of training of interdisciplinary and innovative think-ing for medical postgraduates and proposed many specific programs for interdisciplinary training con-struction including the building of interdisciplinary curriculum system,comprehensive experiment and communication platform,construction of interdisciplinary innovative tutor team,double or multi-tutorial system,interdisciplinary projects,et al.

Objective To study the inhibitory effect of oxymatrine on hepatitis B virus(HBV) in vitro. Methods Microparticle enzyme immunoassay, bDNA signal amplification assay was used for determining secrected HBsAg/HBeAg in the culture medium, HBV DNA from core particles in the cytoplasm and MTT colorimetric assay was used to assay the oxymatrine cytotoxity. Results The inhibitory rates of HBsAg and HBeAg were 40.57% and 48.27% by oxymatrine at the concentration of 2 000 ?g/ml. At 100～2 000 ?g/ml, it can remarkably decrease the level of viral core associated HBV DNA in the cytoplasm. No significant toxicity was shown in such concentrations. Conclusion Oxymatrine has a potential anti HBV activity in vitro.

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.

Objective To investigate the effect of folic acid on the DNA methylation of tumorrelated genes promoters in healthy human peripheral blood mononuclear cells(PBMC). Methods Ten healthy volunteers were divided into two groups, and were randomized to receive either 5 mg folic acid (n=5)or placebo(n = 5) , one time per day for 3 months. The serum folic acid concentration was detected with chemiluminescence enzyme immunoassay kit before and after the intervention. The methylation statuses of five tumor-related genes promoter, including oncogenes c-myc, c-Ha-ras,tumor suppressor genes p16INK4A, E-cadherin and mismatch repair gene hMLH1 in PBMC were detected by bisufite sequencing. Results After folic acid intervention, the level of serum folic acid increased significantly in intervention group (t= -4. 739,P<0. 05) , however no significant difference in control group. After three-month folic acid intervention, the level of methylation of oncogene c-myc promoter increased from 4%, 3. 3%, 4. 1% before intervention, one week after intervention, one month after intervention respectively to 8%(t= -4. 079,P<0. 05), while no significant change in placebo taken group. Before and after the folic acid intervention, there was no significant difference of DNA methylation of other tumor-related genes promoter, including c-Ha-ras、E-cadherin、p16INK4Aand hMLH1. Conclusion Folic acid intervention can up-regulate DNA methylation of oncogene c-myc promoter, but can not affect the promoter methylation status of tumor suppressor genes E-cadherin,p16INK4Aand hMLH1.

Objective To investigate the effects of DNA methylation and histone acetylation on cell cycle progression and expression of tumor suppressor genes in human colonic cancer cells. Methods Three colonic cancer cell lines(HT 29,SW1116 and Colo 320) were treated with the DNA methylation inhibitor, 5 aza 2' deoxycytidine(5 aza dC) and/or the histone deacetylase(HDAC) inhibitor, trichostatin A(TSA)and sodium butyrate. The methylation status of the promoter of the p16 INK4A gene was assayed by methylation specific PCR(MSP). The expression of p16 INK4A and p21 WAF1 were analyzed by RT PCR. Cell cycle distribution was studied by flow cytometry. Results p16 INK4A expression was weakly detected in three colon cancer cells (HT 29,SW1116 and Colo 320) and p21 WAF1 expression was not detected in SW1116 and Colo 320 cells before treatment. The methylation status of the promoter of the p16 INK4A gene was significantly decreased and mRNA expression was markedly increased in HT 29 cells after treatment with 1 ?mol/L but not 10 ?mol/L of 5 aza dC for 24 hours. In SW1116 and Colo 320 cells, the expression of p16 INK4A was obviously enhanced at 10 ?mol/L or 5 ?mol/L of 5 aza dC for 24 hours. However, p21 WAF1 gene expression has not been detected. Interestingly, after treatment of TSA or sodium butyrate, the transcription of p21 WAF1 was significantly up regulated in these two cell lines. In addition, 5 aza dC did not affect cell cycle distribution, but TSA or sodium butyrate blocked cells mainly in the G 1 phases. Conclusions The expression of p16 INK4A gene was regulated by DNA methylation in three human colonic cancer cells. The expression of p21 WAF1 gene was regulated by histone acetylation in SW1116 and Colo 320. In these two cell lines, histone hyperacetylation causes a G 1 cell cycle arrest.

Objective To investigate the relationship between genetic variants in the Toll-like receptor (TLR) pathway genes and susceptibility of gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC).Methods The data of whole genome association studies of the high-risk population of GC and ESCC in China were analyzed by adaptive rank-truncated product (ARTP) method in pathway and gene level.The associations between single nucleotide polymorphism (SNP) and susceptibility of GC and ESCC were analyzed with additive model of unconditional Logistic regressions.PLINK 1.07 and SPSS 19.0 software were performed for statistical analyses,and ARTP package in R3.0.2 was used for pathway and gene level analysis.Results In gene-level analyses,eight genes were found to be associated with susceptibility of GC (P ＜0.05) and six genes were associated with susceptibility of ESCC (P ＜ 0.05).In single SNP-level analyses,21 SNPs were statistically correlated with susceptibility of GC (P ＜ 0.01),and 11 SNPs were statistically correlated with susceptibility of ESCC (P ＜0.01).Conclusions Some genetic variants in TLR pathway are associated with risk of GC and ESCC.The potential molecular mechanisms need further investigation.

Objective To analyze the effect of eukaryotic expression vector containing sense and antisense DNA methyltransferase (DNMT1) gene on the transcript level of tumor associated genes in human colon cancer cell line. Methods Recombinant plasmid, including sense DNMT1 (HMT) and antisense DNMT1 (THM) gene, were constructed and transfected into SW1116 cell by using the lipofectamine. Then G418 filtration was performed. The expression of DNMT1 protein was examined by Western blotting. The transcription level of hMLH1, hMSH2, c myc and p16 INK4A genes were detected by RT PCR. Results The sense and antisense eukaryotic expression vectors were successfully constructed and then the constructed recombinant plasmids were transfected into SW1116 cell. The protein levels of DNMT1 have been up regulated and down regulated in SW1116 cells transfected with HMT and THM plasmids, respectively. The mRNA level of hMLH1, hMSH2, c myc gene were down regulated in the sense DNMT1 transfected cell. The mRNA level of hMSH2 was up regulated in the antisense DNMT1 transfected cell. However, the transcription level of p16 INK4A gene could not be associated with DNMT1 in SW1116 cell.Conclusion DNMT1 can regulate the expression of the tumor associated genes in human colon cancer cell line SW1116.

Educational reform of pathophysiology oriented to clinical application is to pass the physician qualifica -tion examination .One of essential approach is to implement pathophysiology teaching with the translational medical philosophy and promote the harmonious development of physician -patient relationship with the utilization of the de-velopment and changes of disease in the teaching process .In that way, the pathophysiology in basic and clinical medicine is worthy of the name of “bridge”, and ultimately achieves the goal of “the transformation and develop-ment of the cultivation of clinical application talents”.

Objective To study the inhibitory effect of oxymatrine on hepatitis B virus (HBV) in vitro.Methods Microparticle enzyme immunoassay, bDNA signal amplification assay was used for determining secreted HBsAg/HBeAg in the culture medium, HBV DNA from core particles in the cytoplasm and MTT colorimetric assay was used to assay the oxymatrine cytotoxity.Results The inhibitory rates of HBsAg and HBeAg were 40.57% and 48.27% by oxymatrine at the concentration of 2000*!μg/ml. At 100-2000*!μg/ml, it can remarkably decrease the level of viral core associated-HBV DNA in the cytoplasm. No significant toxicity was shown in such concentrations.Conclusion Oxymatrine has a potential anti-HBV activity in vitro.

Ureaplasma is a common pathogen in the human reproductive tract and consists of two distinct biotypes: biotype 1 and biotype 2. In 2002, based on the differences between biotypes, biotype 1 was further classified to a separate species named Ureaplasma parvum (Up), whereas biotype 2 is referred to as Ureaplasma urealyticum (Uu). Uu infection is associated with various urogenital diseases including infertility, preterm birth, and urethritis, while the pathogenicity of Up remains controversial. Researches have shown that different serotypes showed distinct pathogenicity and drug resistance in different diseases and populations, highlighting the importance of clinical tests of serotype and biotype for Ureaplasma. This article reviews the factors that may be associated with Ureaplasma infection, and the current status of the diagnosis and treatment in clinical practice, aiming to provide insights into the clinical significance and necessity of biotypes and serotype tests for Ureaplasma-positive cases and to serve as a reference for the clinical diagnosis and treatment of related diseases.