Study on C/EBPα and FOXC2 expression in colon cancer lesions andpreliminary analysis of their downstream target genes

Objective: To study the C/EBPα and FOXC2 expression in colon cancer lesions and explore their downstream target genes. Methods: Colon cancer specimens surgically removed in Weinan Central Hospital between March 2014 and February 2017 were selected, and adjacent tissue specimens more than 5cm from tumor lesion margin were selected as control. The RNA in the clinical specimens was extracted and the mRNA expression of C/EBPα, FOXC2 as well as endoplasmic reticulum stress molecules and epithelial-mesenchymal transition molecules were determined. Results: C/EBPα, Bax, Bak, GRP78, PERK and ATF6 mRNA expression levels in colon cancer specimens were significantly lower than those in adjacent samples while FOXC2, FAK, SphK1, N-cadherin and Vimentin mRNA expression levels were significantly higher than those in adjacent specimens;Bax, Bak, GRP78, PERK and ATF6 mRNA expression levels in colon cancer specimens with high C/EBPα expression were significantly higher than those in colon cancer specimens with low C/EBPα expression;FAK, SphK1, N-cadherin and Vimentin mRNA expression levels in colon cancer specimens with high FOXC2 expression were significantly higher than those in colon cancer specimens with low FOXC2 expression. Conclusion: Lowly expressed C/EBPα and highly expressed FOXC2 in colon cancer lesions can inhibit the apoptosis mediated by endoplasmic reticulum stress and promote the cell invasion mediated by epithelial-mesenchymal transition.

Donor-specific antibodies,glomerulitis,and human leukocyte antigen B eplet mismatch are risk factors for peritubular capillary C4d deposition in renal allografts

Background:The complement system plays an important role in the immune response to transplantation,and the diagnostic significance of peritubular capillary(PTC)C4d deposition(C4d+)in grafts is controversial.The study aimed to fully investigate the risk factors for PTC C4d+and analyze its significance in biopsy pathology of kidney transplantation.Methods:This retrospective study included 124 cases of kidney transplant with graft biopsy and donor-specific antibody(DSA)testing from January 2017 to December 2019 in a single center.The effects of recipient pathological indicators,eplet mismatch(MM),and DSAs on PTC C4d+were examined using univariate and multivariate logistic regression analyses.Results:In total,35/124(28%)were PTC C4d+,including 21 with antibody-mediated rejection(AMR),eight with renal tubular injury,three with T cell-mediated rejection,one with glomerular disease,and two others.Univariate analysis revealed that DSAs(P<0.001),glomerulitis(P<0.001),peritubular capillaritis(P<0.001),and human leukocyte antigen(HLA)B eplet MM(P=0.010)were the influencing factors of PTC C4d+.According to multivariate analysis,DSAs(odds ratio[OR]:9.608,95%confidence interval[CI]:2.742–33.668,P<0.001),glomerulitis(OR:3.581,95%CI:1.246–10.289,P=0.018),and HLA B eplet MM(OR:1.166,95%CI:1.005–1.353,P=0.042)were the independent risk factors for PTC C4d+.In receiver operating characteristic curve analysis,the area under the curve was increased to 0.831 for predicting PTC C4d+when considering glomerulitis,DSAs,and HLA B eplet MM.The proportions of HLA I DSAs and PTC C4d+in active antibody-mediated rejection were 12/17 and 15/17,respectively;the proportions of HLA class II DSAs and PTC C4d+in chronic AMR were 8/12 and 7/12,respectively.Furthermore,the higher the PTC C4d+score was,the more serious the urinary occult blood and proteinuria of recipients at the time of biopsy.Conclusions:PTC C4d+was mainly observed in AMR cases.DSAs,glomerulitis,and HLA B eplet MM are the independent risk factors for PTC C4d+.

A conceived model of“physician scientist”cultivation:exploring the double degrees of MD-PhD program

To the Editor:With the rapid economic growth and improvement of people's living standards in China,ever-greater demands for high-level health-care services hre expected.These expectations are bringing new challenges to the development of clinical doctors.However,the traditional path for doctor training is inadequate to meet these challenges,as both clinical and scientific practices are important for doctors but difficult to integrate into medical education.Thus,the current medical training system is challenged to combine scientific research training with conventional clinical training.To provide possible sol-utions,Health Science Center(HSC)of Xian Jiaotong University(XJTU)has been exploring a new mode of developing physician scientists:The Double Doctoral Program(DDP)。