Objective To investigate the effects and mechanisms of suppressor of cytokine signaling 3(SOCS3)overexpression on CD4+T cells imbalance in rats with experimental autoimmune myocarditis(EAM).Methods Ten male Lewis rats were randomly select-ed as the control group from 30male Lewis rats.The remaining 20 rats were injected with porcine cardiac myosin on the 0th and 7th days of the experiment to establish the EAM rat model.These 20 rats were then randomly divided into two groups:the EAM group and the EAM+SOCS3group.The EAM+SOCS3group was injected with SOCS3-overexpressing lentivirus via the tail vein,while the EAM group was injected with an equal volume of empty vector lentivirus.All rats underwent echocardiography to evaluate cardiac function and were then euthanized on the 21st day of the experiment.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of serum cardiac troponin T,creatine kinase-myocardial band,B-type natriuretic peptide,and cytokine levels.Myocardial tissue inflam-mation infiltration and myocardial pathological scores were evaluated by hematoxylin-eosin(HE)staining.The levels of CD4+T cell subsets in the rat spleen were detected by flow cytometry.The expressions of SOCS3,Janus kinase 2(JAK2),signal transducer and acti-vator of transcription 3(STAT3),and CD4+T cell-specific transcription factors were detected by real time fluorescent quantitative poly-merase chain reaction(RT-qPCR)and Western blot.Results In the EAM group,the levels of serum of cardiac troponin T,creatine kinase-myocardial band,and B-type natriuretic peptide,were significantly increased compared with those in the control group(P＜0.05),and the myocardial pathological score was significantly increased(P＜0.05);In the EAM group,the mRNA and protein expres-sions of T-box expressed in T cells(T-bet)and retinoid-related orphan receptor γt(RORγt)in myocardial tissues were significantly increased compared with those in the control group(all P＜0.05),while the expression of forkhead box P3(Foxp3)was significantly de-creased(P＜0.05);In the EAM group,the percentages of helper T cell 1(Th1)and helper T cell 17(Th17)in the spleen were signif-icantly increased compared with those in the control group(both P＜0.05),and the percentage of regulatory T cell(Treg)was signifi-cantly decreased(P＜0.05);In the EAM group,the mRNA and protein expressions of JAK2 and STAT3 in myocardial tissues were signifi-cantly increased compared with those in the control group(P＜0.05).These indexes in the EAM+SOCS3group were significantly restored compared with those in the EAM group(P＜0.05).Conclusion SOCS3 overexpression can ameliorate the imbalance of CD4+T cells and alleviate myocardial damage in EAM rats,and its mechanism is related to the downregulation of the JAK2/STAT3signaling pathway.

Objective To investigate the effects and mechanisms of suppressor of cytokine signaling 3(SOCS3)overexpression on CD4+T cells imbalance in rats with experimental autoimmune myocarditis(EAM).Methods Ten male Lewis rats were randomly select-ed as the control group from 30male Lewis rats.The remaining 20 rats were injected with porcine cardiac myosin on the 0th and 7th days of the experiment to establish the EAM rat model.These 20 rats were then randomly divided into two groups:the EAM group and the EAM+SOCS3group.The EAM+SOCS3group was injected with SOCS3-overexpressing lentivirus via the tail vein,while the EAM group was injected with an equal volume of empty vector lentivirus.All rats underwent echocardiography to evaluate cardiac function and were then euthanized on the 21st day of the experiment.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of serum cardiac troponin T,creatine kinase-myocardial band,B-type natriuretic peptide,and cytokine levels.Myocardial tissue inflam-mation infiltration and myocardial pathological scores were evaluated by hematoxylin-eosin(HE)staining.The levels of CD4+T cell subsets in the rat spleen were detected by flow cytometry.The expressions of SOCS3,Janus kinase 2(JAK2),signal transducer and acti-vator of transcription 3(STAT3),and CD4+T cell-specific transcription factors were detected by real time fluorescent quantitative poly-merase chain reaction(RT-qPCR)and Western blot.Results In the EAM group,the levels of serum of cardiac troponin T,creatine kinase-myocardial band,and B-type natriuretic peptide,were significantly increased compared with those in the control group(P＜0.05),and the myocardial pathological score was significantly increased(P＜0.05);In the EAM group,the mRNA and protein expres-sions of T-box expressed in T cells(T-bet)and retinoid-related orphan receptor γt(RORγt)in myocardial tissues were significantly increased compared with those in the control group(all P＜0.05),while the expression of forkhead box P3(Foxp3)was significantly de-creased(P＜0.05);In the EAM group,the percentages of helper T cell 1(Th1)and helper T cell 17(Th17)in the spleen were signif-icantly increased compared with those in the control group(both P＜0.05),and the percentage of regulatory T cell(Treg)was signifi-cantly decreased(P＜0.05);In the EAM group,the mRNA and protein expressions of JAK2 and STAT3 in myocardial tissues were signifi-cantly increased compared with those in the control group(P＜0.05).These indexes in the EAM+SOCS3group were significantly restored compared with those in the EAM group(P＜0.05).Conclusion SOCS3 overexpression can ameliorate the imbalance of CD4+T cells and alleviate myocardial damage in EAM rats,and its mechanism is related to the downregulation of the JAK2/STAT3signaling pathway.

[Abstract] Objective: To investigate the effects of forkhead box transcription factor (FOXK2) overexpression on the proliferation, migration, invasion and adhesion of human ovarian cancer SK-OV-3 cells and its related molecular mechanism. Methods: The open reading frame (ORF) of FOXK2 was cloned into lentivirus expression vector, which was then enveloped in HEK293T cells and transfected into human ovarian cancerSK-OV-3cells.TheoverexpressionefficiencywasdetectedbyqPCRandWesternblotting.Theproliferation, migration, invasion and adhesion of SK-OV-3 cells were detected by CCK-8, Scratch-healing, Transwell and Cell adhesion assays respectively, and the expressions of epithelial-mesenchymal transition (EMT) markers were detected by qPCR. Results: The FOXK2 overexpression vector was constructed successfully and packaged into lentivirus, which was then transfected into SK-OV-3 cells. After transfection, the expression of FOXK2 was significantly increased (P<0.01); the proliferation, migration and invasion of SK-OV-3 cells were significantly reduced while the adhesion ability was significantly increased (P<0.05 or P<0.01); and the expression levels of E-cadherin and β-catenin were significantly increased while that of vimentin and fibronection were significantly decreased (all P<0.01). Conclusion: Overexpression of FOXK2 in SK-OV-3 cells leads to a significant decrease in proliferation, migration and invasion but increase in adhesion. The molecular mechanism may be related to the reversion of the EMT process in tumor cells, suggesting that FOXK2 may be a potential target for the diagnosis and treatment of ovarian cancer.

Objective To investigate the impacts of planning target volume (VPTV),maximal heart distance (MHD),central lung distance (CLD),and cardiothoracic ratio (CTR) on intensity-modulated radiotherapy (IMRT) after breast-conserving surgery for breast cancer.Methods Forty-eight patients with breast cancer (31 with left-sided breast cancer and 17 with right-sided breast cancer) who received whole-breast IMRT after breast-conserving surgery in our hospital from 2016 to 2017 were enrolled as subjects.The prescribed radiation dose tor PTV was 50 Gy in 25 fractions.In IMRT planning for each patient,the objective function was optimized using physical parameters and the equivalent uniform dose.The relationship of influencing factors with dose-volume histogram,conformal index (CI),and homogeneity index (HI) for organ at risk was predicted using univariate and multivariate linear regression analyses.Results CTR and VPTV were independent influencing factors for CI in patients with left-sided breast cancer (R2=0.56,P=0.04;R2 =0.56,P=0.00).CLD was an independent influencing factor for HI in patients with left-sided breast cancer (R2=0.17,P=0.023).VPTV was an independent influencing factor for CI in patients with right-sided breast cancer (R2 =0.48,P=0.00).MHD and CTR were predictors for VHeart30 of the heart.MHD and CLD were predictors for DmaxHeart of the heart.The prediction formulae for left-sided breast cancer were CI=0.38+0.32CTR and HI=1.06+0.02CLD.CI was 0.48 at the right side.At the left side,Vlung20=12.68+3.18CLD,Vlung10=18.78+4.3CLD,Vlung5=26.2+5.2CLD,and Dmeanlung=686.7+210.ICLD.For the heart,VHeart30=-13.65+30.5CTR+1.9MHD and DmaxHeart =5 140.1 +248.9MHD-195.6CLD.There was no correlation of patient's heart volume with MHD,VHeart10,VHeart5,DmeanHeart,or DmaxHeart.There was no correlation of whole lung volume with CLD,Vlung20,Vlung10,Vlung5,or Dmeanlung.The mean values of CI and HI were 0.63± 0.06 (0.46-0.72) and 1.09± 0.02 (1.07-1.14-) in radiotherapy plans for left-sided breast cancer,and 0.65± 0.08 (0.4-8-0.76) and 1.09± 0.04 (1.03-1.18) in radiotherapy plans for right-sided breast cancer,respectively.Conclusions CTR,CLD,and MHD can predict the rationality of each parameter in IMRT planning for left-sided breast cancer rather than right-sided breast cancer.The obtained formulae can help physicians choose the optimal setting mode for radiation field and improve the quality of treatment plans.