AIM:To investigate the role and mechanisms of p21 activated kinase 1(Pak1)in myocardial met-abolic reprogramming(MR)in diabetes mellitus(DM)mice and its protective effects on cardiomyocytes.METHODS:Pak1flox/flox(Pak1f/f)mice and cardiomyocyte-specific Pak1 knockout(Pak1CKO)mice were randomly divided into 4 groups(n=6 per group):Pak1f/f group,Pak1f/f+DM group,Pak1CKO group,and Pak1CKO+DM group.Diabetes was induced by in-traperitoneal injection of streptozotocin.Cardiac function was evaluated by echocardiography 6 weeks after successful mod-eling.Ventricular myocardium was harvested after euthanasia.Myocardial pathological changes and lipid accumulation were assessed by HE staining and oil red O staining.Protein expression levels of Pak1,p-Pak1,peroxisome proliferator-activated receptor α(PPARα),PPARγ,lipoprotein lipase(LPL),carnitine palmitoyltransferase 1(CPT1),scavenger receptor B2(SCARB2/CD36),fatty acid binding protein 3(FABP3),pyruvate dehydrogenase kinase 4(PDK4)and the ratio of phosphorylated pyruvate dehydrogenase E1α subunit(p-PDHA1)to PDHA1 were determined by Western blot.The mRNA expression levels of diacylglycerol acyltransferase 1/2(DGAT1/2)were detected by RT-qPCR.RESULTS:Compared with Pak1f/f group,both Pak1f/f+DM and Pak1CKO groups showed significantly decreased left ventricular ejection fraction(EF)and fractional shortening(FS),as well as increased left ventricular end-diastolic volume(LV Vold)and end-systolic volume(LV Vols)(P<0.01).Significant myocardial pathological damage with excessive lipid accumulation was observed.Myocardial p-Pak1 and Pak1 protein expression decreased(P<0.01),while PPARα,PPARγ,CPT1,LPL,CD36,FABP3,and PDK4 protein expression significantly increased(P<0.01),along with elevated p-PDHA1/PDHA1 ratio(P<0.01).mRNA expression levels of DGAT1 and DGAT2 were significantly reduced(P<0.01).The Pak1CKO+DM group showed the same trend as the Pak1f/f+DM group but with greater severity;compared with the Pak1f/f+DM group,the Pak1CKO+DM group still showed significant differences in all indicators except EF,FS,and LVVold(P<0.05 or P<0.01).CONCLUSION:Myocardial Pak1 protein expression is suppressed in diabetic mice,which mediates MR through activation of the PPARα/γ signaling pathway,resulting in increased myocardial fatty acid uptake and utiliza-tion while reducing glucose oxidation capacity.This leads to lipid accumulation in cardiomyocytes,myocardial damage,and cardiac systolic and diastolic dysfunction.

AIM:To investigate the role and mechanisms of p21 activated kinase 1(Pak1)in myocardial met-abolic reprogramming(MR)in diabetes mellitus(DM)mice and its protective effects on cardiomyocytes.METHODS:Pak1flox/flox(Pak1f/f)mice and cardiomyocyte-specific Pak1 knockout(Pak1CKO)mice were randomly divided into 4 groups(n=6 per group):Pak1f/f group,Pak1f/f+DM group,Pak1CKO group,and Pak1CKO+DM group.Diabetes was induced by in-traperitoneal injection of streptozotocin.Cardiac function was evaluated by echocardiography 6 weeks after successful mod-eling.Ventricular myocardium was harvested after euthanasia.Myocardial pathological changes and lipid accumulation were assessed by HE staining and oil red O staining.Protein expression levels of Pak1,p-Pak1,peroxisome proliferator-activated receptor α(PPARα),PPARγ,lipoprotein lipase(LPL),carnitine palmitoyltransferase 1(CPT1),scavenger receptor B2(SCARB2/CD36),fatty acid binding protein 3(FABP3),pyruvate dehydrogenase kinase 4(PDK4)and the ratio of phosphorylated pyruvate dehydrogenase E1α subunit(p-PDHA1)to PDHA1 were determined by Western blot.The mRNA expression levels of diacylglycerol acyltransferase 1/2(DGAT1/2)were detected by RT-qPCR.RESULTS:Compared with Pak1f/f group,both Pak1f/f+DM and Pak1CKO groups showed significantly decreased left ventricular ejection fraction(EF)and fractional shortening(FS),as well as increased left ventricular end-diastolic volume(LV Vold)and end-systolic volume(LV Vols)(P<0.01).Significant myocardial pathological damage with excessive lipid accumulation was observed.Myocardial p-Pak1 and Pak1 protein expression decreased(P<0.01),while PPARα,PPARγ,CPT1,LPL,CD36,FABP3,and PDK4 protein expression significantly increased(P<0.01),along with elevated p-PDHA1/PDHA1 ratio(P<0.01).mRNA expression levels of DGAT1 and DGAT2 were significantly reduced(P<0.01).The Pak1CKO+DM group showed the same trend as the Pak1f/f+DM group but with greater severity;compared with the Pak1f/f+DM group,the Pak1CKO+DM group still showed significant differences in all indicators except EF,FS,and LVVold(P<0.05 or P<0.01).CONCLUSION:Myocardial Pak1 protein expression is suppressed in diabetic mice,which mediates MR through activation of the PPARα/γ signaling pathway,resulting in increased myocardial fatty acid uptake and utiliza-tion while reducing glucose oxidation capacity.This leads to lipid accumulation in cardiomyocytes,myocardial damage,and cardiac systolic and diastolic dysfunction.

Objective:To evaluate the effect of three teaching methods of case-based learning (CBL), problem-based learning (PBL) and blended learning (CBL+PBL) on the teaching of clinical clerkship of cardiovascular internal medicine among medical students.Methods:A total of 175 third-year medical students were divided into three groups (CBL, PBL and CBL+PBL). They entered the clinical clerkship in batches, and then received written examination and questionnaire survey after the teaching. The data were processed by SPSS 19.0 and were compared by one-way ANOVA or chi-square test (R × C) among groups.Results:The total average scores of students in CBL, PBL and CBL+PBL groups were 15.34±2.88, 14.67±2.98 and 17.13±2.82, respectively ( P<0.05), and the proportion of students with "excellent" scores were 27.4%(17/62), 14.5%(9/62) and 58.1%(36/162), respectively. Most students in CBL group did not agree that CBL helped to train literature access skills [70.7%(41/58)] or teamwork ability [82.8%(48/58)], compared with which 70.9%(39/55) in PBL group thought it helped to train literature access skills but only 7.3%(4/55) well accepted PBL. In addition, majority of students in CBL+PBL group believed it was helpful to gain learning interest [64.3%(36/56)] and train team cooperation ability [62.5%(35/56)], and [53.6%(30/56)] favored this teaching method. Conclusion:Compared with traditional CBL, PBL fails to attract students or improve teaching performance; while blended learning is benefited for the students and can improve teaching quality.

Objective To investigate the impact of body mass index (BMI) on short-term and long-term prognosis in the patients with ST-segment elevation myocardial infarction (STEMI).Methods The clinical data of inpatients with STEMI in our hospital during 2014 were retrospectively collected.The patients conforming to the inclusion and exclusion criteria were divided into 4 groups according to BMI,low BMI group (n=31),normal BMI group (n=139),overweight group (n=71) and obesity group(n=26).The clinical baseline data were analyzed and compared among 4 groups,and the all-cause mortality on 7 d and within 1 year after myocardial infarction(MI) was followed up.Results The higher the BMI increased,the younger the patient's onset age (P＜0.01),the smaller the female proportion(P=0.001),among them,the albumin and hemoglobin levels in the obesity group were relatively higher(P=0.004;P =0.006);the all-cause mortality at 1 year after MI was significantly decreased with BMI increasing (P =0.003),while which on 7 d after MI had no statistical difference (P=0.287).Conclusion BMI is correlated with the long-term prognosis in the patients with STEMI,and "obesity contradiction" phenomenon exists in the patients with STEMI.However,the influence of BMI on the prognosis in the patients with STEMI should be comprehensively evaluated by combining with the multiple factors such as the patient's age,sex,complications and medication therapy.

Objective To study the expression of GRHL-3 in diffuse large B-cell lymphoma (DLBCL) tissues and its clinical significance.Methods One hundred and sixty-eight pathology paraffin-embedded diffuse large B-cell lymphomas tissues were collected from January 2006 to September 2011.Immunohistochemistry was used to detect the expression of GRHL-3 protein in the above tissues.Results The positive expression rate of GRHL-3 protein in the GCB type tissues was higher than that in the non-GCB type tissues [84.87 ％(101/119) vs 14.29 ％ (7/49), P ＜ 0.01].Further analysis indicated that in the non-GCB type tissues,the positive expression rate of GRHL-3 in the latter stage group was significantly higher than that in the early stage group [90.00 ％ (63/70) vs 77.56 ％ (38/49), P ＜ 0.01].The positive expression rate of GRHL-3 in the lactatede hydrogenase increased group was significantly higher than that in the normal lactated hydrogenase [91.67 ％ (77/84) vs 68.57 ％ (24/35), P ＜ 0.01].The positive expression rate of GRHL-3 in the extranodal involvement status ≥ 2 group was significantly higher than that in the extranodal involvement status 0-1 group [96.29 ％ (26/27) vs 81.52 ％ (75/92), P ＜ 0.05].The positive expression rate of GRHL-3 in the IPI score 4-5 group was significantly higher than that in the IPI score 0-1 group [91.30 ％ (65/69) vs 66.67 ％ (18/27), P ＜ 0.01] and IPI score 2-3 group [91.30 ％ (65/69) vs 79.96 ％ (18/23), P ＜ 0.05].However, the expression of GRHL-3 had no correlation with the gender, age, and performance status of DLBCL.Conclusion The positive expression rate of GRHL-3 protein in the GCB type tissues is higher than that in the non-GCB type tissues.The positive expression rate of GRHL-3 in the DLBCL is correlated with the Ann Arbor stage, lactate dehydrogenase, extranodal involvement status and IPI score.