Objective:To investigate the impact of limonin(LIM)on the necrotic apoptosis of myocardial cells in rats with myocardial infarction(MI)by regulating the receptor-interacting protein 1(RIP1)/receptor-interacting protein 3(RIP3)/mixed-lineage kinase domain-like protein(MLKL)signaling pathway.Methods:A total of 60 Sprague-Dawley rats were randomly divided into sham-operation group(Sham group),MI model group(Model group),low-dose LIM group(LIM-L group,25 mg/kg LIM),high-dose LIM group(LIM-H group,50 mg/kg LIM),and high-dose LIM+RIP1 inhibitor Nec-1 group(LIM-H+Nec-1 group,50 mg/kg LIM+0.6 mg/kg Nec-1),with 12 rats in each group.A rat model of MI was established by ligation of the coronary artery.The changes of cardiac func-tion were examined for each group;HE staining was used to observe the pathological changes of myocardial tissue;the 2,3,5-triphen-yltetrazolium chloride-Evans blue method was used to measure myocardial infarct area;the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method was used to observe the necrotic apoptosis of myocardial cells;quantitative real-time PCR and Western blot were used to measure the expression levels of mRNAs and proteins associated with the RIP1/RIP3/MLKL signaling pathway and the expression of apoptosis-related proteins.Results:Compared with the Sham group,the Model group had significant re-ductions in left ventricular ejection fraction,left ventricular systolic pressure,and the expression level of B-cell lymphoma-2(Bcl-2)in myocardial tissue(all P<0.001)and significant increases in left ventricular end-systolic volume,left ventricular end-diastolic pres-sure,left ventricular end-diastolic volume,myocardial infarct area,cell apoptosis rate,the mRNA and protein expression levels of RIP1,RIP3,and MLKL in myocardial tissue,and the protein expression levels of Bcl-2 associated X protein and cysteinyl aspartate-specific proteinase 3 in myocardial tissue(all P<0.001),as well as swelling and disordered arrangement of myocardial cells with ne-crosis and massive inflammatory cell infiltration on HE pathological sections.Compared with the Model group,the LIM-H group showed reverse changes in the above indicators(RIP1 mRNA:P=0.002,RIP3 mRNA:P=0.008,and the other indexes P were all<0.001),with alleviations of myocardial histopathological injury and inflammatory cell infiltration.Nec-1 promoted the effect of LIM in alleviating the necrotic apoptosis of myocardial cells in MI rats.Conclusion:LIM may alleviate the necrotic apoptosis of myocardial cells in MI rats by downregulating the RIP1/RIP3/MLKL signaling pathway.

Objective To investigate the correlation between the peripheral blood levels of long non-coding RNA urothelial carcinoma associated 1(lncRNA UCA1)and miR-665 with the occur-rence of coronary restenosis in patients with ACS after interventional treatment.Methods A total of 315 ACS patients admitted to the Affiliated Hospital of Hebei University from July 2022 to Ju-ly 2023 were recruited and then divided into occurrence group(62 cases)and non-occurrence group(253 cases)according to the occurrence of coronary restenosis.The expression of lncRNA UCA1 and miR-665 in peripheral blood samples was detected by real-time fluorescence quantita-tive PCR.Pearson analysis was applied to analyze the correlation between peripheral blood ln-cRNA UCA1 and miR-665 in ACS patients.Logistic regression analysis was used to identify the influencing factors for coronary restenosis in ACS patients.ROC curve was plotted to analyze the predictive value of peripheral blood lncRNA UCA1 and miR-665 for the restenosis,and their AUC values were calculated.Results The peripheral blood expression of lncRNA UCA1 was signifi-cantly higher,and that of miR-665 was obviously lower in the occurrence group than the non-occurrence group(1.28±0.22 vs 1.01±0.21,P=0.001;0.76±0.24 vs 1.01±0.22,P=0.001).Pearson analysis showed there was a negative correlation between miR-665 and lncRNA UCA1 expression levels in the ACS patients(r=-0.585,P＜0.05).Multivariate logistic regression anal-ysis indicated that LncRNA UCA1 was a risk factor(OR=2.124,95％CI:1.324-3.406,P=0.002),and miR-665 was a protective factor(OR=0.765,95％CI:0.653-0.897,P=0.001)for the occurrence of coronary restenosis in ACS patients after interventional treatment.ROC curve analysis revealed that the combination of peripheral blood lncRNA UCA1 and miR-665 had the highest AUC value in predicting the occurrence of coronary restenosis,which was better than the value of single molecule(Z=2.256,P=0.024;Z=2.904,P=0.004).Conclusion Combination of peripheral blood levels of lncRNA UCA1 and miR-665 has good performance for predicting coro-nary restenosis in ACS patients after interventional therapy.

Objective To investigate the effect and underlying mechanism of miR-137 on athero-sclerosis(AS)plaques in apolipoprotein E(ApoE)gene knockout(ApoE)mice.Methods Sixty ApoE-/-mice were fed with high-fat diet for 12 weeks to establish an AS model.Then they were assigned into AS group,negative control group,miR-137 group,Ad negative control group,and combination group,with 12 mice in each group;Another 12 wild-type C57BL/6 mice fed with chow diet were subjected as the Control group.Fully automated biochemical analyzer was applied to detect serum lipid levels,including total cholesterol(TC),triglycerides(TG),low-density lipo-protein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C).ELISA was con-ducted to detect the levels of serum inflammatory factors,including TNF-α,IL-4,IL-6,and IL-10.HE staining was used to observe the morphological changes of mouse aortic tissue.Oil red O stai-ning was employed to observe the overall formation of aortic plaques.Immunofluorescence stai-ning was utilized to detect the expression of inducible nitric oxide synthase(iNOS)and arginase-1(Arg-1)in the aortic tissue.Real-time qPCR was applied to detect the mRNA expression of miR-137 and sex determining region Y box protein 4(SOX4)in the aorta.Results The miR-137 group has significantly lower serum levels of TG,TC,LDL-C,TNF-α and IL-6,and higher levels of HDL-C,IL-10 and IL-4 when compared with the AS group and negative control group(P＜0.05).The combination treatment resulted in increased serum levels of TG,TC,LDL-C,TNF-αand IL-6,while decreased levels of HDL-C,IL-10 and IL-4 in comparison with the Ad negative control group(P＜0.05).Larger aortic plaque area,more severe overall aortic plaque injury and stronger iNOS fluorescence intensity were observed in the AS group than the control group(P＜0.05).Treatment of miR-137 reversed above histological changes,resulting in smaller aortic plaque area,attenuated overall aortic plaque injury,decreased iNOS fluorescence intensity,and elevated Arg-1 fluorescence intensity when compared with the AS group and negative control group(P＜0.05).Compared with the Ad negative control group,the aortic plaque area,overall aortic plaque injury and iNOS fluorescence intensity were increased,while the Arg-1 fluorescence intensity was significantly decreased in the combined group(P＜0.05).Double luciferase assay showed that the luciferase activity of SOX4-containing wild-type cells was significantly decreased after transfection of miR-137 mimics when compared with transfection of mimics negative control(0.37±0.05 vs 1.00±0.08,P＜0.05).Conclusion Overexpression of miR-137 inhibits the activa-tion of rat sarcoma/mitogen-activated protein kinase pathway probably by down-regulating SOX4 expression,and then suppress M1 macrophage polarization and promote M2 macrophage polariza-tion,reduces inflammatory response and the formation of AS plaques.

Objective To investigate the correlation between the peripheral blood levels of long non-coding RNA urothelial carcinoma associated 1(lncRNA UCA1)and miR-665 with the occur-rence of coronary restenosis in patients with ACS after interventional treatment.Methods A total of 315 ACS patients admitted to the Affiliated Hospital of Hebei University from July 2022 to Ju-ly 2023 were recruited and then divided into occurrence group(62 cases)and non-occurrence group(253 cases)according to the occurrence of coronary restenosis.The expression of lncRNA UCA1 and miR-665 in peripheral blood samples was detected by real-time fluorescence quantita-tive PCR.Pearson analysis was applied to analyze the correlation between peripheral blood ln-cRNA UCA1 and miR-665 in ACS patients.Logistic regression analysis was used to identify the influencing factors for coronary restenosis in ACS patients.ROC curve was plotted to analyze the predictive value of peripheral blood lncRNA UCA1 and miR-665 for the restenosis,and their AUC values were calculated.Results The peripheral blood expression of lncRNA UCA1 was signifi-cantly higher,and that of miR-665 was obviously lower in the occurrence group than the non-occurrence group(1.28±0.22 vs 1.01±0.21,P=0.001;0.76±0.24 vs 1.01±0.22,P=0.001).Pearson analysis showed there was a negative correlation between miR-665 and lncRNA UCA1 expression levels in the ACS patients(r=-0.585,P＜0.05).Multivariate logistic regression anal-ysis indicated that LncRNA UCA1 was a risk factor(OR=2.124,95％CI:1.324-3.406,P=0.002),and miR-665 was a protective factor(OR=0.765,95％CI:0.653-0.897,P=0.001)for the occurrence of coronary restenosis in ACS patients after interventional treatment.ROC curve analysis revealed that the combination of peripheral blood lncRNA UCA1 and miR-665 had the highest AUC value in predicting the occurrence of coronary restenosis,which was better than the value of single molecule(Z=2.256,P=0.024;Z=2.904,P=0.004).Conclusion Combination of peripheral blood levels of lncRNA UCA1 and miR-665 has good performance for predicting coro-nary restenosis in ACS patients after interventional therapy.

Objective To investigate the effect and underlying mechanism of miR-137 on athero-sclerosis(AS)plaques in apolipoprotein E(ApoE)gene knockout(ApoE)mice.Methods Sixty ApoE-/-mice were fed with high-fat diet for 12 weeks to establish an AS model.Then they were assigned into AS group,negative control group,miR-137 group,Ad negative control group,and combination group,with 12 mice in each group;Another 12 wild-type C57BL/6 mice fed with chow diet were subjected as the Control group.Fully automated biochemical analyzer was applied to detect serum lipid levels,including total cholesterol(TC),triglycerides(TG),low-density lipo-protein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C).ELISA was con-ducted to detect the levels of serum inflammatory factors,including TNF-α,IL-4,IL-6,and IL-10.HE staining was used to observe the morphological changes of mouse aortic tissue.Oil red O stai-ning was employed to observe the overall formation of aortic plaques.Immunofluorescence stai-ning was utilized to detect the expression of inducible nitric oxide synthase(iNOS)and arginase-1(Arg-1)in the aortic tissue.Real-time qPCR was applied to detect the mRNA expression of miR-137 and sex determining region Y box protein 4(SOX4)in the aorta.Results The miR-137 group has significantly lower serum levels of TG,TC,LDL-C,TNF-α and IL-6,and higher levels of HDL-C,IL-10 and IL-4 when compared with the AS group and negative control group(P＜0.05).The combination treatment resulted in increased serum levels of TG,TC,LDL-C,TNF-αand IL-6,while decreased levels of HDL-C,IL-10 and IL-4 in comparison with the Ad negative control group(P＜0.05).Larger aortic plaque area,more severe overall aortic plaque injury and stronger iNOS fluorescence intensity were observed in the AS group than the control group(P＜0.05).Treatment of miR-137 reversed above histological changes,resulting in smaller aortic plaque area,attenuated overall aortic plaque injury,decreased iNOS fluorescence intensity,and elevated Arg-1 fluorescence intensity when compared with the AS group and negative control group(P＜0.05).Compared with the Ad negative control group,the aortic plaque area,overall aortic plaque injury and iNOS fluorescence intensity were increased,while the Arg-1 fluorescence intensity was significantly decreased in the combined group(P＜0.05).Double luciferase assay showed that the luciferase activity of SOX4-containing wild-type cells was significantly decreased after transfection of miR-137 mimics when compared with transfection of mimics negative control(0.37±0.05 vs 1.00±0.08,P＜0.05).Conclusion Overexpression of miR-137 inhibits the activa-tion of rat sarcoma/mitogen-activated protein kinase pathway probably by down-regulating SOX4 expression,and then suppress M1 macrophage polarization and promote M2 macrophage polariza-tion,reduces inflammatory response and the formation of AS plaques.

Objective To explore changes of left atrial(LA)volume and function in ankylosing spondylitis(AS)patients with different activity by using ultrasound four-dimensional auto LA quantification(4D Auto LAQ)technique.Methods Eighty-nine AS patients were retrospectively selected and divided into remission group(group A,n=20),low activity group(group B,n=25),high activity group(group C,n=23)and very high activity group(group D,n=21)according to AS disease activity score-C reactive protein(ASDAS-CRP).Meanwhile,54 healthy adults with age and gender matched were recruited as control group.Conventional echocardiographic parameters and LA volume and strain parameters obtained with 4D Auto LAQ technique were compared among groups.Multiple ordinal logistic regression was used to analyze the correlations of LA volume and strain parameters with AS disease activity.Results The ratio of early diastolic peak flow velocity of mitral orifice to early diastolic velocity of lateral mitral annulus(E/e')and LA minimum volume(LAVmin),the maximum volume(LAVmax),presystolic volume(LAVpre),ejection fraction(LAEF),active ejection fraction(LAaEF)and passive ejection fraction(LApEF)were all significantly different among groups,so were LA longitudinal strain during reservoir phase(LASr-l),conduit phase(LAScd-l),contraction phase(LASct-l)and circumferential strain during reservoir phase(LASr-c),conduit phase(LAScd-c)and contraction phase(LASct-c)(all P＜0.001).LAVmin was positively correlated(OR=7.106,B=1.96),while LASr-l and LASct-l were negatively correlated with AS activity(OR=0.235,0.145,B=-1.44,-1.93).Conclusion With the increase of disease activity,LAVmin in AS patients gradually increased,while LASr-l and LASct-l gradually decreased.

Objective To explore changes of left atrial(LA)volume and function in ankylosing spondylitis(AS)patients with different activity by using ultrasound four-dimensional auto LA quantification(4D Auto LAQ)technique.Methods Eighty-nine AS patients were retrospectively selected and divided into remission group(group A,n=20),low activity group(group B,n=25),high activity group(group C,n=23)and very high activity group(group D,n=21)according to AS disease activity score-C reactive protein(ASDAS-CRP).Meanwhile,54 healthy adults with age and gender matched were recruited as control group.Conventional echocardiographic parameters and LA volume and strain parameters obtained with 4D Auto LAQ technique were compared among groups.Multiple ordinal logistic regression was used to analyze the correlations of LA volume and strain parameters with AS disease activity.Results The ratio of early diastolic peak flow velocity of mitral orifice to early diastolic velocity of lateral mitral annulus(E/e')and LA minimum volume(LAVmin),the maximum volume(LAVmax),presystolic volume(LAVpre),ejection fraction(LAEF),active ejection fraction(LAaEF)and passive ejection fraction(LApEF)were all significantly different among groups,so were LA longitudinal strain during reservoir phase(LASr-l),conduit phase(LAScd-l),contraction phase(LASct-l)and circumferential strain during reservoir phase(LASr-c),conduit phase(LAScd-c)and contraction phase(LASct-c)(all P＜0.001).LAVmin was positively correlated(OR=7.106,B=1.96),while LASr-l and LASct-l were negatively correlated with AS activity(OR=0.235,0.145,B=-1.44,-1.93).Conclusion With the increase of disease activity,LAVmin in AS patients gradually increased,while LASr-l and LASct-l gradually decreased.

Objective:To evaluate right atrial (RA) volume and function in patients with hepatitis B cirrhosis by four-dimensional automatic quantitation analysis technique, and to explore its correlation with liver function grading.Methods:Ninety patients with hepatitis B cirrhosis who were clinically confirmed in Henan Provincial People′s Hospital from December 2020 to July 2021 were randomly enrolled as the research subjects. According to Child-Pugh liver function score criteria, the patients were divided into three groups: Child-Pugh A group ( n=31), Child-Pugh B group ( n=31), Child-Pugh C group ( n=28). Another 30 healthy volunteers with gender and age matched at the same period were selected as the control group. The RA maximum volume (RAVmax), RA minimum volume (RAVmin), RA presystolic volume (RAVpreA), RA maximum volume index (RAVImax), RA emptying volume (RAEV), RA ejection fraction (RAEF), RA reservoir longitudinal and circumferential strains (RASr, RASr-c), RA conduit longitudinal and circumferential strains (RAScd, RAScd-c), RA contraction longitudinal and circumferential strains (RASct, RASct-c) were obtained by four-dimensional automatic quantitation analysis technique. Spearman correlation analysis was used to explore the correlation between the volume and strain parameters of right atrium and liver function grading, and the independent correlation factors of RASr-c were analyzed by univariate and multivariate linear regression analyses. Results:Compared with the control group, Child-Pugh A and Child-Pugh B groups, RAVmax, RAVmin, RAVpreA, RAVImax, and RAEV were all increased in Child-Pugh C group (all P<0.05). Compared with control group, the absolute values of RASr, RASct, RASr-c and RASct-c were increased, and the absolute values of RAScd and RAScd-c were decreased in Child-Pugh A group (all P<0.05). Compared with control group, Child-Pugh A and Child-Pugh B groups, the absolute values of RASr, RAScd, RASct, RASr-c, RAScd-c and RASct-c were decreased in the Child-Pugh C group (all P<0.05). Correlation analysis showed that the volume and strain parameters of the right atrium were correlated with liver function grading. RASr-c was independently correlated with E/e, ALB and BNP(β=-0.543, 0.521, and -0.562 respectively, all P<0.05). Conclusions:During the compensatory stage in patients with hepatitis B cirrhosis, the RA functions of reservoir and contractile were increased, but the function of conduit was decreased. With the aggravation of liver cirrhosis, the RA functions of reservoir, conduit and contractile were all decreased. The four-dimensional volume and strain parameters of the right atrium were correlated with Child-Pugh liver function grading, and RASr-c was independently correlated with E/e, ALB and BNP.

Objective:To establish a predictive model for preoperative diagnosis of benign and malignant phyllodes tumor of the breast(PTB). Methods:The clinicopathological data of 69 patients with benign PTB and 41 patients with malignant PTB(24 borderline and 17 malignant)who underwent multiple(≥2)preoperative ultrasound follow-ups in the Cancer Hospital of Harbin Medical University from January 2011 to December 2018 were retrospectively analyzed.The preoperative prediction models of benign and malignant PTB were constructed by using the influencing factors determined by multivariate logistic regression analysis.The receiver operating characteristic(ROC)curve was used to evaluate the efficiency of the prediction model.In addition,the clinicopathological data of 22 patients of benign PTB and 19 patients of malignant PTB(12 borderline and 7 malignant)admitted to the hospital from January 2019 to April 2022 were selected for external verification. Results:Logistic regression analysis showed that growth rate of tumor>2 mm/month and ultrasound BI-RADS category≥4b were independent predictors for the diagnosis of malignant PTB(OR:4.476,95％CI:1.673～11.975;OR:9.448,95％CI:3.149～28.345;P<0.01).The logistic regression equation:Logit(P)=-1.868+1.499×growth rate of tumor+2.246×ultrasound BI-RADS category.The AUC for the training cohort was 0.795(95％CI:0.699～0.890),the best cut-off value was 0.421,the corresponding sensitivity was 0.732,the specificity was 0.826,and the Jorden index was 0.558,P<0.001.The AUC for the the validation cohort was 0.772(95％CI:0.624～0.919),with the sensitivity of 0.526 and the specificity of 0.773,positive predictive value was 0.667 and negative predictive value was 0.654,P = 0.003.The AUC of the training cohort and the validation cohort were both>0.75,indicating that the model has certain predictive ability. Conclusion:The predictive model constructed by clinicopathological parameters can be used for preoperative diagnosis of benign PTB and malignant PTB,and provide a certain reference value for clinicians to select the appropriate surgical resection scope.

Humans ; Arthroplasty, Replacement, Knee/adverse effects* ; Arthritis, Rheumatoid/surgery* ; Risk Factors ; Patients ; Arthroplasty, Replacement, Hip/adverse effects*