AIM:To explore the role and molecular mechanism of Men1 gene in regulating mouse renal fibro-sis.METHODS:A unilateral ureteral obstruction(UUO)-induced renal fibrosis model was established using C57BL/6 mice,and the mice were randomly divided into 4 groups:sham,UUO-3 d,UUO-7 d,and UUO-14 d,with 15 mice in each group.The C57BL/6 mice with Men1 knockout were randomly divided into 4 groups:sham-Men1-WT,sham-Men1-CKO,UUO-Men1-WT,and UUO-Men1-CKO,with 8 mice in each group.HE staining,Masson staining,and Sirius red staining were used to detect UUO-induced renal injury and renal fibrosis.Human renal tubular epithelial HK-2 cells with MEN1 knockout were constructed.RT-qPCR,Western blot,immunohistochemistry and immunoflurorescnence were per-formed to detect the mRNA and protein expression of MEN1,fibrosis markers(α-smooth muscle actin,collagen type Ⅲ and fibronectin 1)and m6A-related proteins[methyltransferase-like 3(METTL3),METTL14,YTH domain family pro-tein 2(YTHDF2),AlkB homolog 5(ALKBH5),and fat mass and obesity-associated protein(FTO)]in UUO mouse kid-ney tissues and transforming growth factor-β(TGF-β;10 μg/L)-treated HK-2 cells.Dot blot analysis was conducted to measure m6A methylation levels in both mouse kidney tissuess and HK-2 cells.RESULTS:The expression of Men1 de-creased with the aggravation of renal fibrosis(P＜0.01).Men1 inhibited the expression of fibrosis markers in renal tis-sues,and MEN1 knockout increased the accumulation of collagen induced by UUO and TGF-β(P＜0.01).The expres-sion of FTO and ALKBH5 in mouse kidney tissues and HK-2 cells was down-regulated by MEN1 knockout(P＜0.01),and the methylation level of m6A was increased(P＜0.01).Overexpression of FTO significantly reduced the accumulation of m6A modifications and renal fibrosis caused by MEN1 loss,and the methylation level of m6A was increased(P＜0.01).CONCLUSION:Loss of Men1 gene promotes renal fibrosis in mice,and Men1 suppresses renal fibrosis in mice by pro-moting the expression of FTO/ALKBH5 to reduce m6A modifications.

AIM:To explore the role and molecular mechanism of Men1 gene in regulating mouse renal fibro-sis.METHODS:A unilateral ureteral obstruction(UUO)-induced renal fibrosis model was established using C57BL/6 mice,and the mice were randomly divided into 4 groups:sham,UUO-3 d,UUO-7 d,and UUO-14 d,with 15 mice in each group.The C57BL/6 mice with Men1 knockout were randomly divided into 4 groups:sham-Men1-WT,sham-Men1-CKO,UUO-Men1-WT,and UUO-Men1-CKO,with 8 mice in each group.HE staining,Masson staining,and Sirius red staining were used to detect UUO-induced renal injury and renal fibrosis.Human renal tubular epithelial HK-2 cells with MEN1 knockout were constructed.RT-qPCR,Western blot,immunohistochemistry and immunoflurorescnence were per-formed to detect the mRNA and protein expression of MEN1,fibrosis markers(α-smooth muscle actin,collagen type Ⅲ and fibronectin 1)and m6A-related proteins[methyltransferase-like 3(METTL3),METTL14,YTH domain family pro-tein 2(YTHDF2),AlkB homolog 5(ALKBH5),and fat mass and obesity-associated protein(FTO)]in UUO mouse kid-ney tissues and transforming growth factor-β(TGF-β;10 μg/L)-treated HK-2 cells.Dot blot analysis was conducted to measure m6A methylation levels in both mouse kidney tissuess and HK-2 cells.RESULTS:The expression of Men1 de-creased with the aggravation of renal fibrosis(P＜0.01).Men1 inhibited the expression of fibrosis markers in renal tis-sues,and MEN1 knockout increased the accumulation of collagen induced by UUO and TGF-β(P＜0.01).The expres-sion of FTO and ALKBH5 in mouse kidney tissues and HK-2 cells was down-regulated by MEN1 knockout(P＜0.01),and the methylation level of m6A was increased(P＜0.01).Overexpression of FTO significantly reduced the accumulation of m6A modifications and renal fibrosis caused by MEN1 loss,and the methylation level of m6A was increased(P＜0.01).CONCLUSION:Loss of Men1 gene promotes renal fibrosis in mice,and Men1 suppresses renal fibrosis in mice by pro-moting the expression of FTO/ALKBH5 to reduce m6A modifications.

Objective To test the expression of serine/arginine rich splicing factor 1(SRSF1)and apoptosis inhibiting factor(Survivin) in prostate cancer,and study their correlation with the pathological features of prostate cancer,so as to put forward the new targets in the treatment of prostate cancer. Methods SRSF1 and Survivin protein was determined in 20 prostate tissue samples including prostate cancer(n=12)and benign prostat?ic hyperplasia(n=8)by immunohistochemical SP method. SRSF1 and Survivin was correlated to pathological features,and both the relevance was analyzed(no related reports at home and abroad). Results The positive expression rate of SRSF1 protein in prostate cancer tissue cells was 76.37± 5.06%,which was significantly higher than that of benign prostatic hyperplasia(11.30%±1.09%,P<0.05);the positive expression rate of Survivin protein in prostate cancer tissue cells was 86.93%±3.21%,which was significantly higher than that of benign prostatic hyperplasia(17.67%±1.99%, P<0.05);SRSF1 and Survivin protein expressed in prostate cancer organizations and were positively correlated to pathological Gleason grading, and there was significant correlation(P<0.05). Conclusion SRSF1 and Survivin protein were highly expressed in adenocarcinoma tissue,which were significantly increased than that of benign hyperplasia of prostate tissue. The positive expression SRSF1 and Survivin protein were positively cor?related to pathological Gleason grading.The expression of Survivin protein was elevated with the expression of SRSF1 protein in prostate cancer. These preliminary evidence indicated that SRSF1 may up?regulate the expression of Survivin,and thus promote the occurrence and development of prostate cancer.

Objective To investigate the relationship between the tube voltage and radiation dose as well as image quality in adult upper airway digital radiography (DR).Methods We used CDRAD2.0 contrast details phantom and PMMA to simulate adult upper airway. With different tube voltages,the phantom was exposed using automatic exposure control system (AEC).The entrance surface dose( ESD),dose area product(DAP) and mAs in every exposures were recorded.The image quality factors(IQF) of all images were calculated. Results With tube voltage increasing,ESD,DAP,mAs decreased and IQF value enhanced.There were statistically significance ( F =45.15,26.41,29.26,56.53,P ＜ 0.05 ).ESD,DAP,mAs significantly increased with tube voltage less than 75 kV,began to decrease when tube voltage more than 75 kV,tended to be on the balance in 75 -80 kV.At the same time,the fluctuation of IQF value was no statistical difference in 50 - 75 kV of tube voltage,but was statistical significance in 75 -90 kV( F =11.35,P ＜0.05 ).So,the image quality of adult upper airway with different tube voltage had no significant difference.Conclusions The appropriate tube voltage was 75 kV to 80 kV in the upper airway DR.The IQF value can be provided as the clinical evaluation index of image quality.