Background The benefit/risk ratio of stenting in acute ST-segment elevation myocardial infarction (STEMI) patients with single vessel intermediate stenosis culprit lesions merits further study, therefore the subject...Background The benefit/risk ratio of stenting in acute ST-segment elevation myocardial infarction (STEMI) patients with single vessel intermediate stenosis culprit lesions merits further study, therefore the subject of the present study. Methods and results It was a pro- spective, multicenter, randomized controlled trial. Between April 2012 and July 2015, 399 acute STEMI patients with single vessel disease and intermediate (40%-70%) stenosis of the culprit lesion before or after aspiration thrombectomy and/or intracoronary tirofiban (15 pg/kg) were enrolled and were randomly assigned (h 1) to stenting group (n = 201) and non-stenting group (n = 198). In stenting group, patients received pharmacologic therapy plus standard percutaneous coronary intervention (PCI) with stent implantation. In non-stenting group, pa- tients received pharmacologic therapy and PCI (thrombectomy), but without dilatation or stenting. Primary endpoint was 12-month rate of major adverse cardiac and eerebrovascular events (MACCE), a composite of cardiac death, non-fatal myocardial infarction (M1), repeat re- vascularization and stroke. Secondary endpoints were 12-month rates of all cause death, ischemia driven admission and bleeding complica- tion. Median follow-up time was 12.4 ~ 3.1 months. At 12 months, MACCE occurred in 8.0% of the patients in stenting group, as compared with 15.2% in the non-stenting group (adjusted HR: 0.42, 95% Ch 0.19-0.89, P = 0.02). The stenting group had lower non-fatal MI rate than non-stenting group, (1.5% vs. 5.5%, P = 0.03). The two groups shared similar cardiac death, repeat revascularization, stroke, all cause death, ischemia driven readmission and bleeding rates at 12 months. Conclusions Stent implantation had better efficacy and safety in reducing MACCE risks among acute STEMI patients with single vessel intermediate stenosis culprit lesions.展开更多
Objective: To explore the effect of dysregulation of epigenetic regulator EZH1 and EZH2 on the proliferation in MCL and the underlying mechanisms.Methods: In this study, we elucidated the role of EZH1 and EZH2 overexp...Objective: To explore the effect of dysregulation of epigenetic regulator EZH1 and EZH2 on the proliferation in MCL and the underlying mechanisms.Methods: In this study, we elucidated the role of EZH1 and EZH2 overexpression by immunohistochemistry and correlated them to clinical outcome in 41 MCL patients.Quantitative real-time PCR and Western blot were applied to confirm the level of EZH1 and EZH2 in well-characterized MCL cell lines which were compared to those of na?ve B cells.Then we manipulated the expression of EZH1 and EZH2 in MCL cells using CRISPR/Cas9 system to directly investigate their functional roles in MCL.We also evaluated the effect of two small molecule selective inhibitors, EPZ005687 and UNC1999, on MCL cell proliferation, cell cycle distribution and apoptosis in vitro.Finally, we performed RNA-sequencing(RNA-Seq) and Chromatin immunoprecipitation(ChIP) assay to further gain insight into the underlying molecular mechanisms.Results: We found that EZH2 protein is overexpressed in approximately half of this cohort of MCL cases.More importantly, the overexpression of EZH2 is associated with poor OS in the patients.Nevertheless, simple EZH2 depletion in vitro has little impact on the viability of MCL cells, predominantly because of the consequent up-regulation of EZH1.Consistently, UNC1999, a dual EZH1/2 inhibitor, unlike the EZH2 selective inhibitor EPZ005687, exerts a potent inhibitory effect on MCL cells.Furthermore, we discover CDKN1C and TP53 INP1 as the two important cell cycle regulators, the expression of which are repressed by EZH1/2 mediated epigenetic regulation and are restored by EZH1/2 dual inhibition.Conclusions: Our study suggests that EZH2 participates in the pathogenesis of MCL which may serve as a potential biomarker for prognosis prediction.The dual inhibition of EZH1/2 is a promising therapeutic strategy for MCL.展开更多
Acute myocardial infarction complicated by cardiogenic shock and left main coronary artery disease is called left main shock syndrome. It is reported that the morbility and mortality of the syndrome is approximately 0...Acute myocardial infarction complicated by cardiogenic shock and left main coronary artery disease is called left main shock syndrome. It is reported that the morbility and mortality of the syndrome is approximately 0.46%and 55%-80%, respectively. However, the best treat-ment strategy in these cases is unknown. In this article, we present a patient with LMSS who successively underwent emergency percutane-ous coronary intervention and coronary artery bypass grafting with hemodynamic support within 5 days. The patient is now on his three month uneventful out-patient follow-up.展开更多
Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is the cornerstone of acute myocardial infarction(AMI)management,both invasive and conservative.[1,2]This dual strategy improved ischemic outcomes but was o...Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is the cornerstone of acute myocardial infarction(AMI)management,both invasive and conservative.[1,2]This dual strategy improved ischemic outcomes but was offset by an increased bleeding risk.The prognostic importance of bleeding events has been well established over the past decades,as several studies have shown a strong association between bleeding and mortality.[3]The CRUSADE score is superior to other scores in predicting in-hospital major bleeding events.In this regard,in its non-ST elevation acute coronary syndromes(NSTE-ACS)guidelines,the European Society of Cardiology(ESC)stated that the CRUSADE score could be considered for bleeding risk quantification of coronary angiography in NSTE-ACS patients(class IIb,level B evidence).[4]However,the most common site of spontaneous.展开更多
Anaerobic digestion is one of the effective ways to dispose of antibiotic pharmaceutical waste. However,the inhibition of antibiotics on anaerobic fermentation microorganisms seriously hinders the normal physiological...Anaerobic digestion is one of the effective ways to dispose of antibiotic pharmaceutical waste. However,the inhibition of antibiotics on anaerobic fermentation microorganisms seriously hinders the normal physiological activities of anaerobic microorganisms and then affects the efficiency of anaerobic digestion. In order to solve this problem,related scholars have done a lot of research. It has been found that pretreatment of anaerobic microorganisms and antibiotic pharmaceutical waste can significantly improve the efficiency of anaerobic digestion. In this paper,the current feasible pretreatment methods were summarized,and the application of different pretreatment methods was analyzed to provide reference for improving pretreatment methods and improving anaerobic biological treatment ability of antibiotic waste.展开更多
Background: Recent studies show that microRNA- 145 (miRNA- 145 ) might be an attractive tumor biomarker of considerable prognostic value, but little is known about their relationship with acute myocardial infarcti...Background: Recent studies show that microRNA- 145 (miRNA- 145 ) might be an attractive tumor biomarker of considerable prognostic value, but little is known about their relationship with acute myocardial infarction (AMI). This study investigated the correlation between the level of miR-145 and AM1. Methods: One-hundred patients were divided into three groups: no coronary artery disease (CAD) group, non-ST segment elevation myocardial infarction group, and ST segment elevation myocardial infarction group. The plasma levels of miR-145 were quantified using real-time quantitative polymerase chain reaction. Logarithmic transformation of miRNA-145 levels (Ln_rniRNA-145) was used for statistical analysis due to the skewed data distribution. Results: Plasma levels of miR-145 were significantly lower in patients with AMI compared to patients in the non-CAD group (-6.38 ± 0.11 vs. -4.47 + 0.17, P 〈 0.0001). Compared to those without heart failure, the levels of miR-145 were significantly lower in patients with heart failure (-6.91 ± 0.20 vs. -5.35 ± 0.13, P 〈 0.0001). We also found that the lower plasma levels of miRNA-145 significantly correlated with increased serum levels of B-type natriuretic peptide (Spearman ρ = -0.60, P 〈 0.0001), troponin T (Spearman p = -0.62, P 〈 0.0001), and decreased ejection fraction (Spearman ρ = 0.65, P 〈 0.0001). In a multivariable linear regression analysis, AMI and heart failure were independently associated with lower Ln miRNA-145 (estimate -0.99, standard error [SE] 0.28; P = 0.001 and estimate -0.62, SE 0.21 ; P = 0.004). Conclusions: Our results suggest that decreased plasma levels of miR-145 are associated with AMI. Circulating miR-145 may be useful in prognosticating cardiac function and the risk of developing heart failure.展开更多
To the Editor:Cardiac implantable electrical devices(CIEDs)are the most effective method of treating and diagnosing several different kinds of arrhythmia and heart failure.It is necessary for a clinician to evaluate t...To the Editor:Cardiac implantable electrical devices(CIEDs)are the most effective method of treating and diagnosing several different kinds of arrhythmia and heart failure.It is necessary for a clinician to evaluate the parameters of the device to ensure safety and efficacy during the procedure.Traditionally,parameter testing and programming are performed by the manufacturer’s clinical service technician on-site in the Cath-lab.However,after the outbreak of the corona virus disease-2019(COVID-19),the manufacturer’s clinical service technicians are not allowed access to the Cath-lab and ward.Solving the problemof parameter testing and programming is crucial.展开更多
Dear Editor,Cytidine analogs,such as decitabine(DAC)and cytarabine(ara-C),have been widely used in the clinical treatment for several cancer types,including myelodysplastic syndrome and acute myeloid leukemia(AML;Appe...Dear Editor,Cytidine analogs,such as decitabine(DAC)and cytarabine(ara-C),have been widely used in the clinical treatment for several cancer types,including myelodysplastic syndrome and acute myeloid leukemia(AML;Appelbaum et al.1999;Saba 2007).However,drug resistance causing treatment failure and disease relapse is an unresolved problem to date.Certain cancer cells rely on the salvage enzymes cytidine deaminase(CDA)and dCMP deaminase(DCTD)to inactivate these cytidine derivative drugs by deamination(Jamieson et al.1987;Ebrahem et al.2012).It is imperative to develop new categories of chemotherapeutic nucleosides to overcome the drug resistance caused by such increased cellular deamination activity.展开更多
文摘Background The benefit/risk ratio of stenting in acute ST-segment elevation myocardial infarction (STEMI) patients with single vessel intermediate stenosis culprit lesions merits further study, therefore the subject of the present study. Methods and results It was a pro- spective, multicenter, randomized controlled trial. Between April 2012 and July 2015, 399 acute STEMI patients with single vessel disease and intermediate (40%-70%) stenosis of the culprit lesion before or after aspiration thrombectomy and/or intracoronary tirofiban (15 pg/kg) were enrolled and were randomly assigned (h 1) to stenting group (n = 201) and non-stenting group (n = 198). In stenting group, patients received pharmacologic therapy plus standard percutaneous coronary intervention (PCI) with stent implantation. In non-stenting group, pa- tients received pharmacologic therapy and PCI (thrombectomy), but without dilatation or stenting. Primary endpoint was 12-month rate of major adverse cardiac and eerebrovascular events (MACCE), a composite of cardiac death, non-fatal myocardial infarction (M1), repeat re- vascularization and stroke. Secondary endpoints were 12-month rates of all cause death, ischemia driven admission and bleeding complica- tion. Median follow-up time was 12.4 ~ 3.1 months. At 12 months, MACCE occurred in 8.0% of the patients in stenting group, as compared with 15.2% in the non-stenting group (adjusted HR: 0.42, 95% Ch 0.19-0.89, P = 0.02). The stenting group had lower non-fatal MI rate than non-stenting group, (1.5% vs. 5.5%, P = 0.03). The two groups shared similar cardiac death, repeat revascularization, stroke, all cause death, ischemia driven readmission and bleeding rates at 12 months. Conclusions Stent implantation had better efficacy and safety in reducing MACCE risks among acute STEMI patients with single vessel intermediate stenosis culprit lesions.
基金supported by a grant from the National Natural Science Foundation of China (Grant No.81372539)
文摘Objective: To explore the effect of dysregulation of epigenetic regulator EZH1 and EZH2 on the proliferation in MCL and the underlying mechanisms.Methods: In this study, we elucidated the role of EZH1 and EZH2 overexpression by immunohistochemistry and correlated them to clinical outcome in 41 MCL patients.Quantitative real-time PCR and Western blot were applied to confirm the level of EZH1 and EZH2 in well-characterized MCL cell lines which were compared to those of na?ve B cells.Then we manipulated the expression of EZH1 and EZH2 in MCL cells using CRISPR/Cas9 system to directly investigate their functional roles in MCL.We also evaluated the effect of two small molecule selective inhibitors, EPZ005687 and UNC1999, on MCL cell proliferation, cell cycle distribution and apoptosis in vitro.Finally, we performed RNA-sequencing(RNA-Seq) and Chromatin immunoprecipitation(ChIP) assay to further gain insight into the underlying molecular mechanisms.Results: We found that EZH2 protein is overexpressed in approximately half of this cohort of MCL cases.More importantly, the overexpression of EZH2 is associated with poor OS in the patients.Nevertheless, simple EZH2 depletion in vitro has little impact on the viability of MCL cells, predominantly because of the consequent up-regulation of EZH1.Consistently, UNC1999, a dual EZH1/2 inhibitor, unlike the EZH2 selective inhibitor EPZ005687, exerts a potent inhibitory effect on MCL cells.Furthermore, we discover CDKN1C and TP53 INP1 as the two important cell cycle regulators, the expression of which are repressed by EZH1/2 mediated epigenetic regulation and are restored by EZH1/2 dual inhibition.Conclusions: Our study suggests that EZH2 participates in the pathogenesis of MCL which may serve as a potential biomarker for prognosis prediction.The dual inhibition of EZH1/2 is a promising therapeutic strategy for MCL.
文摘Acute myocardial infarction complicated by cardiogenic shock and left main coronary artery disease is called left main shock syndrome. It is reported that the morbility and mortality of the syndrome is approximately 0.46%and 55%-80%, respectively. However, the best treat-ment strategy in these cases is unknown. In this article, we present a patient with LMSS who successively underwent emergency percutane-ous coronary intervention and coronary artery bypass grafting with hemodynamic support within 5 days. The patient is now on his three month uneventful out-patient follow-up.
文摘Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is the cornerstone of acute myocardial infarction(AMI)management,both invasive and conservative.[1,2]This dual strategy improved ischemic outcomes but was offset by an increased bleeding risk.The prognostic importance of bleeding events has been well established over the past decades,as several studies have shown a strong association between bleeding and mortality.[3]The CRUSADE score is superior to other scores in predicting in-hospital major bleeding events.In this regard,in its non-ST elevation acute coronary syndromes(NSTE-ACS)guidelines,the European Society of Cardiology(ESC)stated that the CRUSADE score could be considered for bleeding risk quantification of coronary angiography in NSTE-ACS patients(class IIb,level B evidence).[4]However,the most common site of spontaneous.
基金Supported by 2017 Innovation Project of Jilin Academy of Agricultural Sciences(c72083203)
文摘Anaerobic digestion is one of the effective ways to dispose of antibiotic pharmaceutical waste. However,the inhibition of antibiotics on anaerobic fermentation microorganisms seriously hinders the normal physiological activities of anaerobic microorganisms and then affects the efficiency of anaerobic digestion. In order to solve this problem,related scholars have done a lot of research. It has been found that pretreatment of anaerobic microorganisms and antibiotic pharmaceutical waste can significantly improve the efficiency of anaerobic digestion. In this paper,the current feasible pretreatment methods were summarized,and the application of different pretreatment methods was analyzed to provide reference for improving pretreatment methods and improving anaerobic biological treatment ability of antibiotic waste.
文摘Background: Recent studies show that microRNA- 145 (miRNA- 145 ) might be an attractive tumor biomarker of considerable prognostic value, but little is known about their relationship with acute myocardial infarction (AMI). This study investigated the correlation between the level of miR-145 and AM1. Methods: One-hundred patients were divided into three groups: no coronary artery disease (CAD) group, non-ST segment elevation myocardial infarction group, and ST segment elevation myocardial infarction group. The plasma levels of miR-145 were quantified using real-time quantitative polymerase chain reaction. Logarithmic transformation of miRNA-145 levels (Ln_rniRNA-145) was used for statistical analysis due to the skewed data distribution. Results: Plasma levels of miR-145 were significantly lower in patients with AMI compared to patients in the non-CAD group (-6.38 ± 0.11 vs. -4.47 + 0.17, P 〈 0.0001). Compared to those without heart failure, the levels of miR-145 were significantly lower in patients with heart failure (-6.91 ± 0.20 vs. -5.35 ± 0.13, P 〈 0.0001). We also found that the lower plasma levels of miRNA-145 significantly correlated with increased serum levels of B-type natriuretic peptide (Spearman ρ = -0.60, P 〈 0.0001), troponin T (Spearman p = -0.62, P 〈 0.0001), and decreased ejection fraction (Spearman ρ = 0.65, P 〈 0.0001). In a multivariable linear regression analysis, AMI and heart failure were independently associated with lower Ln miRNA-145 (estimate -0.99, standard error [SE] 0.28; P = 0.001 and estimate -0.62, SE 0.21 ; P = 0.004). Conclusions: Our results suggest that decreased plasma levels of miR-145 are associated with AMI. Circulating miR-145 may be useful in prognosticating cardiac function and the risk of developing heart failure.
文摘To the Editor:Cardiac implantable electrical devices(CIEDs)are the most effective method of treating and diagnosing several different kinds of arrhythmia and heart failure.It is necessary for a clinician to evaluate the parameters of the device to ensure safety and efficacy during the procedure.Traditionally,parameter testing and programming are performed by the manufacturer’s clinical service technician on-site in the Cath-lab.However,after the outbreak of the corona virus disease-2019(COVID-19),the manufacturer’s clinical service technicians are not allowed access to the Cath-lab and ward.Solving the problemof parameter testing and programming is crucial.
基金supported by the National Natural Science Foundation of China(Nos.32000894,32000420)the Ministry of Science and Technology of China(No.2018YFA0800302)+5 种基金the China postdoctoral Science Foundation(No.2019M651357)the Shanghai Sailing Program(No.18YF1412200)the Chinese Academy of Sciences Interdisciplinary Innovation Team(No.JCTD-2018-14)the Natural Science Foundation of Shanghai(NO.20ZR1408000)Fudan University Start-up Research Grant(Nos.IDH1340038,IDH1340045,IDH1340046,IDH1340059)the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(CIFMS,No.2019-I2M-5-077).
文摘Dear Editor,Cytidine analogs,such as decitabine(DAC)and cytarabine(ara-C),have been widely used in the clinical treatment for several cancer types,including myelodysplastic syndrome and acute myeloid leukemia(AML;Appelbaum et al.1999;Saba 2007).However,drug resistance causing treatment failure and disease relapse is an unresolved problem to date.Certain cancer cells rely on the salvage enzymes cytidine deaminase(CDA)and dCMP deaminase(DCTD)to inactivate these cytidine derivative drugs by deamination(Jamieson et al.1987;Ebrahem et al.2012).It is imperative to develop new categories of chemotherapeutic nucleosides to overcome the drug resistance caused by such increased cellular deamination activity.