FTO improves myocardial fibrosis by reducing m6A modification of DKK2 and promoting DKK2 expression / 西安交通大学学报(医学版)

【Objective】 To explore the relationship of fat mass and obesity-associated protein (FTO) with the m6A modification and expression level of DKK2 in the process of myocardial fibrosis. 【Methods】 Cardiac fibroblasts (CFs) were grouped as follows: Control group, AngⅡ-treated group, AngⅡ+EV group (transfected with empty vector and negative control siRNA and then treated with AngⅡ), AngⅡ+FTO-O group (transfected with FTO overexpression vector and then treated with AngⅡ), and AngⅡ+FTO-O+DKK2 siRNA group (treated with AngⅡ after co-transfection of FTO overexpression vector and DKK2 siRNA). Mice were divided into the following groups: Control group (sham operation group), AMI group (constructing acute myocardial infarction model), AMI+EV group (AMI mice were intraperitoneally injected with nanoparticles containing empty vector), and AMI+FTO-O group (AMI mice were intraperitoneally injected with nanoparticles containing FTO overexpression vector). Then, the expressions of FTO and DKK2 were detected by fluorescence quantitative PCR and Western blotting, the m6A modification level of DKK2 was detected by RNA binding protein immunoprecipitation, the cell viability was detected by CCK-8, the cardiac function of AMI mice was evaluated, and the cardiac pathological changes of mice were detected by HE and Masson staining. 【Results】 AngⅡ inhibited the expression of FTO, thereby enhancing the m6A modification level of DKK2 and downregulating the expression of DKK2 (P<0.05). AngⅡ promoted cell viability and enhanced the expressions of α-SMA, collagen Ⅰ and collagen Ⅲ (P<0.05). FTO overexpression significantly blocked the above-mentioned regulatory effects of AngⅡ (P<0.05), but DKK2 siRNA could antagonize the effect of FTO overexpression on AngⅡ. The expressions of FTO and DKK2 were downregulated in AMI mice, and the m6A modification level of DKK2 was increased (P<0.05). When FTO was overexpressed, the expressions of FTO and DKK2 in AMI mice were significantly restored, the m6A modification level of DKK2 and myocardial fibrosis were significantly reduced (P<0.05), and the cardiac pathological changes were significantly improved. 【Conclusion】 FTO can promote the expression of DKK2 by reducing the m6A modification level of DKK2, thereby inhibiting the progression of myocardial fibrosis. This indicates that FTO/DKK2 pathway is a key pathway in regulating myocardial fibrosis.

Clinical observation on blood coagulation and fibrinolysis in acute leukemia / 第三军医大学学报

Plasma prekallikrein,total fibrinolytic activity (TFA),plasmi-nogen (PLG),fibrinogen (Fbg) and fibrin(ogen) degradation products (FDP) were determined with chromogenic peptide substrate (CPS) and routine hema-tologic methods in 20 patients with untreated acute leukemia.It was found that the activities of blood coagulation and fibrinolysis showed no significant difference between leukemic patients and the normal controls;marked elevation of FDP and Fbg was observed in leukemic patients;the activity of fibrinolysis was significantly higher in the leukemic cases with severe bleeding than in those cases with slight or little bleeding.In addition,a tendency of continuous lowering of FDP.and Fbg levels was observed in a dynamic observation of 3 acute leukemic cases.On the basis of these findings,it might be concluded that no activation of the fibrinolysis system occurs in most cases of acute leukemia;excessive fibrinolysis may be one of the factors to induce severe hemorrhage;the levels of FDP and Fbg are lower in the patients in remission stage than in those in active or relapse stage.Successive determination of FDP and Fbg levels is helpful to assess the conditions of a leukemic patient.

Practical Criteria for Prediction of Responses to Chemotherapy in 90 patients with Acute Leukemias / 第三军医大学学报

Five clinical criteria, including the size of the liver, spleen, and lymph nodes, tenderness over the sternum, and hemorrhagic tendency, the white cell and platelet counts, the bone marrow picture, and the marrow blast decrease index (MBDI) were studied in 90 patients with acute leukemia prior to and after chemotherapy to predict the therapeutic effects.It is concluded that in the 4th week after the commencement of chemotherapy, if there is amelioration of the 5 clinical criteria, steady increase of platelets or with a rebounding peak, improvement of the bone marrow proliferation, and MBDI over 41%, it is an indication that there will be a remission of the disease. If, on the contrary, the 5 criteria shows no amelioration, the white count exceeds 50?109/L, the platelet count decreases markedly, bone marrow proliferation demonstrates no improvement, and MBDI is below 40%, then the possibility to have remission is very little.This method for the prediction the therapeutic responses in leukemic patients is simple, practical, and reliable. The comprehensive analysis of the 9 items cai exercise the function of mutual compensation and render the prediction more precise

Hemogram and Clinical Observation before and after FetalLiver Cell Suspension Infusion in the Treatmentof Some Hematological Diseases / 第三军医大学学报

Recent change of blood pictures by self-control and clinical observation before and after fetal liver cell suspension infusion (FLI) in the treatment of 46 patients with hematological diseases for 130 person-times in recent two years were reported.There were 64 episodes fo FLI in chemotherapy group. Two weeks after FLI, WBC and BPC rose quickly to more than 20% in 75% and 70% of cases respec-were significant differences of WBC and BPC when compared to the self-control group with chemotherapy only(P