To investigate the feasibility and effectiveness of establishing porcine ischemia-reperfusion models by ligating the left anterior descending(LAD)coronary artery,we first randomly divided 16 male Bama pigs into a sham...To investigate the feasibility and effectiveness of establishing porcine ischemia-reperfusion models by ligating the left anterior descending(LAD)coronary artery,we first randomly divided 16 male Bama pigs into a sham group and a model group.After anesthesia,we separated the arteries and veins.Subsequently,we rapidly located the LAD coronary artery at the beginning of its first diagonal branch through a mid-chest incision.Then,we loosened and released the ligation line after five minutes of pre-occlusion.Finally,we ligated the LAD coronary artery in situ two minutes later and loosened the ligature 60 min after ischemia.Compared with the sham group,electrocardiogram showed multiple continuous lead ST-segment elevations,and ultrasound cardiogram showed significantly lower ejection fraction and left ventricular fractional shortening at one hour and seven days post-operation in the model group.Twenty-four hours after the operation,cardiac troponin T and creatine kinase-MB isoenzyme levels significantly increased in the model group,compared with the sham group.Hematoxylin and eosin staining showed the presence of many inflammatory cells infiltrating the interstitium of the myocardium in the model group but not in the sham group.Masson staining revealed a significant increase in infarct size in the ischemia/reperfusion group.All eight pigs in the model group recovered with normal sinus heart rates,and the survival rate was 100%.In conclusion,the method can provide an accurate and stable large animal model for preclinical research on ischemia/reperfusion with a high success rate and homogeneity of the myocardial infarction area.展开更多
Cardiac troponin-I （cTnI） and -T （cTnT） are sensitive and specific markers of myocardial injury. However, the role of increased cTnI and cTnT in percutaneous coronary intervention （PCI）-related myocardial injury...Cardiac troponin-I （cTnI） and -T （cTnT） are sensitive and specific markers of myocardial injury. However, the role of increased cTnI and cTnT in percutaneous coronary intervention （PCI）-related myocardial injury remains controversial. In this prospective, single-center and double-blind study, we aimed to determine the diagnostic and prognostic value of cTnI as well as cTnT （cTns） in PCI-related myocardial injury in a Chinese population. A total of 1,008 patients with stable angina pectoris and non-ST-segment elevation acute coronary syndrome were recruited. The levels of cTnI and cTnT were examined before and after PCI. All patients were followed up for 26± 9 months to observe the incidence of major adverse cardiac events （MACEs）. Our results showed that post- PCI cTnI and/or cTnT levels were increased to more than the 99^th percentile upper reference limit （URL） in 133 （13.2%） patients, among which 22 （2.2%） were more than 5 × 99^th percentile URL. By univariate analysis, an elevation in cTns after PCI was not an independent predictor of increased MACEs, HR 1.35 （P = 0.33, 95% CI： 0.74-2.46）. In conclusion, our data demonstrate that the incidence of PCI-related myocardial injury is not common in a Chinese population and minor elevated cTns levels may not be a sensitive prognostic marker for MACEs.展开更多
Objective：To investigate the effect of cardiomyocyte proliferation induced by human hepatocyte growth factor（HGF）in pigs with chronic myocardial infarction（CMI）.Methods：A steerable,deflectable 7F catheter incorp...Objective：To investigate the effect of cardiomyocyte proliferation induced by human hepatocyte growth factor（HGF）in pigs with chronic myocardial infarction（CMI）.Methods：A steerable,deflectable 7F catheter incorporating a 27-guage needle was advanced percutaneously to the left ventricular myocardium of 18 pigs with CMI.Pigs were randomized（1：1：1）to receive adenoviral vector HGF（total dose,1×10^10 genome copies）,which was administered as five injections into the infarcted myocardium（total,1.0 mL）,or saline,or Ad-null（control groups）.Injections were guided by Ensite NavX left ventricular electroanatomical mapping.HGF and cyclin proteins were detected by western blot and immunoprecipitation analysis.Histological and immunohistochemical analysis determined proliferating cardiomyocytes.Myocardial perfusion and cardiac function were estimated by Gated-Single Photon Emission Computed Tomography（G-SPECT）.Results：Western blot analyses showed that HGF were predominantly expressed in the infarct core and border in the myocardium of the infarcted heart.G-SPECT analysis indicated that the HGF group had better cardiac function and myocardial perfusion four weeks after the injection of Ad-HGF than before the injection of Ad-HGF.After treatment there were more proliferating cardiomyocytes in the HGF group compared to either of the control groups.Furthermore,the HGF group myocardial samples expressed higher levels of p-Akt,cyclin A,cyclin E,cyclin D1,cdk2,cdk4 than those in the control groups.Conclusion：The over-expression of HGF activates pro-survival pathways,induces cardiomyocyte proliferation,and improves the perfusion and function of the porcine CMI heart.展开更多
Objective： Calcium-sensing receptors （CaSRs） are G-protein coupled receptors which maintain systemic calcium homeostasis and participate in hormone secretion, activation of ion channels, cell apoptosis, proliferati...Objective： Calcium-sensing receptors （CaSRs） are G-protein coupled receptors which maintain systemic calcium homeostasis and participate in hormone secretion, activation of ion channels, cell apoptosis, proliferation, and differentiation. Previous studies have shown that CaSRs induce apoptosis in isolated adult rat heart and in normal neonatal rat cardiomyocytes by G-protein-PLC-IP3 signaling transduction. However, little knowledge is presently available concerning the role of CaSRs in the apoptosis induced by ischemia and reperfusion in neonatal cardiomyocytes. Methods： Primary neonatal rat ventricular cardiomyocytes were incubated in ischemiamimetic solution for 2 h, and then re-incubated in normal culture medium for 24 h to establish a model of simu- lated ischemia/reperfusion （I/R）. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase- mediated dUTP nick end labeling （TUNEL）. The expression of CaSRs mRNA was detected by real-time reverse transcription polymerase chain reaction （RT-PCR）. In addition, the expressions of caspase-3 and Bcl-2 were analyzed by western blot. Results： The simulated I/R enhanced the expression of CaSRs and cardiomyocyte apoptosis. GdCl3, a specific activator of CaSRs, further increased the expression of CaSRs and cardiomyocyte apoptosis, along with up-regulation of caspase-3 and down-regulation of Bcl-2. Conclusion： CaSRs are associated with UR injury and apoptosis in neonatal rat ventricular cardiomyocytes via suppressing Bcl-2 and promoting caspase-3 expression.展开更多
We report a case of a 49-year-old man who was admitted with a 3-hour history of sudden onset of substemal chest pain. Coronary angiography revealed that the left circumflex artery （LCX） was acutely and totally occlu...We report a case of a 49-year-old man who was admitted with a 3-hour history of sudden onset of substemal chest pain. Coronary angiography revealed that the left circumflex artery （LCX） was acutely and totally occluded at the mid-portion. In addition, the proximal and mid-portion of the right coronary artery （RCA） had a 60% occlusion. We inferred that the LCX was the culprit artery and primary PCI was successfully performed. Six weeks later, the patient had an eventful course with recurrence of chest pain. Coronary angiography showed no significant ste- nosis in the previous LCX lesion, while the proximal and middle potion of the RCA had a 90% occlusion. Our case demonstrates the systemic nature of acute coronary syndromes and highlights the inherent instability of coronary artery disease.展开更多
The purpose of this study was to assess the relationship between arterial stiffness, as measured by brachial-ankle pulse wave velocity （baPWV）, and the presence of the metabolic syndrome （MS） in a Chinese populati...The purpose of this study was to assess the relationship between arterial stiffness, as measured by brachial-ankle pulse wave velocity （baPWV）, and the presence of the metabolic syndrome （MS） in a Chinese population. A total of 4,445 subjects were enrolled. The prevalence of MS in for the general population, males and females, respectively. our study population was 21.7%, 17.2% and 25.6% With adjustments for age, gender, cigarette smoking, heart rate, total cholesterol, low-density lipoprotein （LDL） cholesterol, and the use of anti-hypertensive drug, the stepwise regression analysis showed that baPWV had a significant relationship with components of MS, including systolic blood pressure （P 〈 0.001）, diastolic blood pressure （P 〈 0.001）, glucose （P 〈 0.001）, highdensity lipoprotein （HDL） cholesterol （P = 0.04）, and triglycerides （P 〈 0.001）, but no relationship with waist circumference （P = 0.25）. With an increase in the number of the MS components, baPWV increased significantly both in women and men. This study indicated that the MS is indeed a risk factor for arterial stiffness. Monitoring of baPWV in patients with MS may help in identifying persons at high risk for cardiovascular disease.展开更多
Objective： To evaluate the effect of transplanting bone marrow-derived mesenchymal stem cells （BM-MSCs） or adenovirus5- hepatocyte growth factor（Ad5-HGF） via non-infarct-related artery injection in swine myocardi...Objective： To evaluate the effect of transplanting bone marrow-derived mesenchymal stem cells （BM-MSCs） or adenovirus5- hepatocyte growth factor（Ad5-HGF） via non-infarct-related artery injection in swine myocardial infarction models. Methods：BMMSCs were obtained from swine bone marrow and expanded in vitro to a purity of 〉50%. A myocardial infarction（MI） was created by ligating the distal left anterior descending artery in swine. Either BM-MSCs （5 × 10^6/ml） or Ad5-HGF （4 × 10^9 pfu） were transfused via the right coronary artery （non-infarcted artery） four weeks after MI. Gate-controled cardiac perfusion imaging was performed at the end of four and seven weeks after LAD ligation, to evaluate heart function and cardiac perfusion. Morphologic and histologic characteristics of the hearts were also studied. Results： （1）The gate-controlled cardiac perfusion imaging showed that the improvement in LVEF was greater in both treatment groups than in control group at the 4^th weeks. （2）In both treatment groups, capillary density was significantly higher than that of control group（P 〈 0.05）. Conclusion ：BM-MSCs or Ad5-HGF transplantation via non-infarcted artery administration can stimulate angiogenesis and improve heart function, but there was no difference in therapeutic efficacy between BM-MSCs and Ad5-HGF.展开更多
This paper introduces the recent progress in methodologies and their related applications based on the soft x-ray interference lithography beamline in the Shanghai synchrotron radiation facility.Dual-beam,multibeam in...This paper introduces the recent progress in methodologies and their related applications based on the soft x-ray interference lithography beamline in the Shanghai synchrotron radiation facility.Dual-beam,multibeam interference lithography and Talbot lithography have been adopted as basic methods in the beamline.To improve the experimental performance,a precise real-time vibration evaluation system has been established;and the lithography stability has been greatly improved.In order to meet the demands for higher resolution and practical application,novel experimental methods have been developed,such as high-order diffraction interference exposure,high-aspect-ratio and large-area stitching exposure,and parallel direct writing achromatic Talbot lithography.As of now,a 25 nm half-pitch pattern has been obtained;and a cm2 exposure area has been achieved in practical samples.The above methods have been applied to extreme ultraviolet photoresist evaluation,photonic crystal and surface plasmonic effect research,and so on.展开更多
Dear Editor： Chronic total occlusions （CTOs） of the coronary artery are commonly encountered complex lesionst11. Percutaneous coronary intervention （PCI） for CTO is technically challenging due to low procedural ...Dear Editor： Chronic total occlusions （CTOs） of the coronary artery are commonly encountered complex lesionst11. Percutaneous coronary intervention （PCI） for CTO is technically challenging due to low procedural success ratesTM. Microcatheter is one of the important devices for treatment of CTOTM. It has been widely used attributed to the excellent crossability whenever angula- tion and tortuousity of the coronary artery is encoun- tered. In the process, the microcatheter has to be withdrawn from the guide wire after the wire is proved to locate in the true lumen.展开更多
Objective： To investigate the role of glutathione S-transferase （GST） genetic variants and markers of oxidative stress and inflammation in smokingrelated coronary artery disease （CAD） patients. Methods： Five hun...Objective： To investigate the role of glutathione S-transferase （GST） genetic variants and markers of oxidative stress and inflammation in smokingrelated coronary artery disease （CAD） patients. Methods： Five hundred and thirty-five Chinese CAD patients were successfully genotyped. Plasma total antioxidant status （TAOS）, glutathione, C-reactive protein （CRP）, fibrinogen（FIB） and white blood cell count （WBC） were determined to evaluate the oxidative stress and inflammatory response. Results： GSTM1-0/ GSTT1-0 subjects had a higher CRP, FIB, WBC and GSH and a lower TAOS compared to patients with wild-type GSTM1/GSTT1 genes, but there was significant difference only with regards to TAOS. Smokers with the null genotype of GSTT1 had the highest CRP and the lowest TAOS and GSH when compared to the GSTTI-1 genotype with smoking status, or the GSTT1-0 genotype with non-smoking status, or the GSTTI-I genotype with non-smoking status. However, we found no significant difference between these groups. Also, no significant interaction was observed between genotypes and smoking status in determining CRP levels. Conclusion： Our results suggest that GST polymorphisms do not modify the effect of smoking on markers of oxidative stress and inflammation in Chinese CAD patients.展开更多
Achromatic Talbot lithography(ATL)with high resolution has been demonstrated to be an excellent technique for large area periodic nano-fabrication.In this work,the uniformity of pattern distribution in ATL was studied...Achromatic Talbot lithography(ATL)with high resolution has been demonstrated to be an excellent technique for large area periodic nano-fabrication.In this work,the uniformity of pattern distribution in ATL was studied in detail.Two ATL transmission masks with^50%duty cycle in a square lattice were illuminated by a spatial coherent broadband extreme ultraviolet beam with a relative bandwidth of 2.38%.Nonuniform dot size distribution was observed by experiments and finite-difference time-domain simulations.The sum of the two kinds of diffraction patterns,with different lattice directions(45°rotated)and different intensity distributions,results in the final nonuniform pattern distribution.展开更多
Background and Aims:Unfractionated heparin(UFH)and bivalirudin are widely used as anticoagulants in cardiovascular medicine,including for thrombosis prevention during coronary angiography(CAG)and percutaneous coronary...Background and Aims:Unfractionated heparin(UFH)and bivalirudin are widely used as anticoagulants in cardiovascular medicine,including for thrombosis prevention during coronary angiography(CAG)and percutaneous coronary intervention(PCI).Little is known of the effects of UFH and bivalirudin on liver and kidney function in patients subjected to these procedures.This study compared the effects of bivalirudin and UFH on liver/renal function in patients with coronary artery disease who underwent CAG,with or without PCI.Methods:The study comprised 134 consecutive patients(40–89 years-old),who underwent CAG(or CAG and PCI);among them,66 and 68 patients were subject to,respectively,bivalirudin or UFH.The following indicators of liver/renal function were measured before and after the procedures:plasma alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen,estimated glomerular filtration rate(eGFR),creatinine clearance,and serum creatinine.Patients were further stratified by severity of chronic kidney disease(CKD),based on original eGFR.Results:Relative to baseline,in the bivalirudin group,ALT and AST were higher after CAG(p=0.005,0.025),while blood urea nitrogen and serum creatinine were lower(p=0.049,<0.001).In the UFH group,ALT,AST,eGFR,and creatinine clearance were lower after CAG(p≤0.001,all).Patients given bivalirudin with moderate or severe CKD,but not those with mild CKD,gained significant improvement in kidney function.Conclusions:Relative to UFH,bivalirudin may better safeguard the renal function of patients with coronary artery disease who undergo CAG,especially patients with moderate-to-severe renal insufficiency.UFH may cause less liver damage than bivalirudin.展开更多
Polybrominated diphenyl ether congeners (PBDEs) might activate the AhR (aromatic hydrocarbon receptor) signal transduction, and thus might have an adverse effect on the health of humans and wildlife. Because of the li...Polybrominated diphenyl ether congeners (PBDEs) might activate the AhR (aromatic hydrocarbon receptor) signal transduction, and thus might have an adverse effect on the health of humans and wildlife. Because of the limited experimental data, it is important and necessary to develop structure-based models for prediction of the toxicity of the compounds. In this study, a new molecular structure representation, molecular hologram, was employed to investigate the quantitative relationship between toxicity and molecular structures for 18 PBDEs. The model with the significant correlation and robustness (r <sup>2</sup> = 0.991, q <sup>2</sup> <sub>LOO</sub> = 0.917) was developed. To verify the robustness and prediction capacity of the derived model, 14 PBDEs were randomly selected from the database as the training set, while the rest were used as the test set. The results generated under the same modeling conditions as the optimal model are as follows: r <sup>2</sup> = 0.988, q <sup>2</sup> <sub>LOO</sub> = 0.598, r <sup>2</sup> <sub>pred</sub> = 0.955, and RMSE (root-mean-square of errors) = 0.155, suggesting the excellent ability of the derived model to predict the toxicity of PBDEs. Furthermore, the structural features and molecular mechanism related to the toxicity of PBDEs were explored using HQSAR color coding.展开更多
Endocrine disrupting chemicals (EDCs) in the natural environment exhibit a unique non-monotonic dose-response curve and it is impossible to select one simple index to characterize the bilogogical activity of these com...Endocrine disrupting chemicals (EDCs) in the natural environment exhibit a unique non-monotonic dose-response curve and it is impossible to select one simple index to characterize the bilogogical activity of these compounds. Quantitative structure-activity relationship (QSAR) study on non-monotonic dose-response curve has become a real challenge presently. In order to explore the possible mechanism for the non-monotonic dose-response curve of polychlorinated biphenyls congeners (PCBs) in chicken embryo hepatocyte bioassay, AM1 method of ChemOffice was adopted to calculate necessary structure descriptors for PCBs, while the interactions between PCBs and simulated AhR ligand binding domain (LBD) were analyzed by using FlexX in SYBYL7.0. Different binding modes for PCBs have been distinguished not only from aligned conformation but also from free binding energy. Some QSAR models were established separately for both low and high doses ranges, revealing that receptor binding may predominate in the interference of the physiological function of cytochrome P4501A-P4501A in the low doses range. But with the higher doses range, the EROD suppression might be related to acute toxicity owing to molecular polarity or distribution of charges and consequently damage structure and function of chicken embryo hepatocyte.展开更多
Cardiovascular disease(CVD)remains the leading cause of death worldwide.Therefore,exploring the mechanism of CVDs and critical regulatory factors is of great significance for promoting heart repair,reversing cardiac r...Cardiovascular disease(CVD)remains the leading cause of death worldwide.Therefore,exploring the mechanism of CVDs and critical regulatory factors is of great significance for promoting heart repair,reversing cardiac remodeling,and reducing adverse cardiovascular events.Recently,significant progress has been made in understanding the function of protein kinases and their interactions with other regulatory proteins in myocardial biology.Protein kinases are positioned as critical regulators at the intersection of multiple signals and coordinate nearly every aspect of myocardial responses,regulating contractility,metabolism,transcription,and cellular death.Equally,reconstructing the disrupted protein kinases regulatory network will help reverse pathological progress and stimulate cardiac repair.This review summarizes recent researches concerning the function of protein kinases in CVDs,discusses their promising clinical applications,and explores potential targets for future treatments.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant No.82070367).
文摘To investigate the feasibility and effectiveness of establishing porcine ischemia-reperfusion models by ligating the left anterior descending(LAD)coronary artery,we first randomly divided 16 male Bama pigs into a sham group and a model group.After anesthesia,we separated the arteries and veins.Subsequently,we rapidly located the LAD coronary artery at the beginning of its first diagonal branch through a mid-chest incision.Then,we loosened and released the ligation line after five minutes of pre-occlusion.Finally,we ligated the LAD coronary artery in situ two minutes later and loosened the ligature 60 min after ischemia.Compared with the sham group,electrocardiogram showed multiple continuous lead ST-segment elevations,and ultrasound cardiogram showed significantly lower ejection fraction and left ventricular fractional shortening at one hour and seven days post-operation in the model group.Twenty-four hours after the operation,cardiac troponin T and creatine kinase-MB isoenzyme levels significantly increased in the model group,compared with the sham group.Hematoxylin and eosin staining showed the presence of many inflammatory cells infiltrating the interstitium of the myocardium in the model group but not in the sham group.Masson staining revealed a significant increase in infarct size in the ischemia/reperfusion group.All eight pigs in the model group recovered with normal sinus heart rates,and the survival rate was 100%.In conclusion,the method can provide an accurate and stable large animal model for preclinical research on ischemia/reperfusion with a high success rate and homogeneity of the myocardial infarction area.
基金supported by the Health Bureau of Jiangsu Province(No.K201104)the Scientific Support Plan of Jiangsu Province(No.BE2011803)+2 种基金the National Natural Science Foundation of China(No.81170102/H0203)the Priority Academic Program Development of Jiangsu Higher Education Institutions(No.BL2012011)the Fourth Period Project"333"of Jiangsu Province(No.BRA2012207),China
文摘Cardiac troponin-I （cTnI） and -T （cTnT） are sensitive and specific markers of myocardial injury. However, the role of increased cTnI and cTnT in percutaneous coronary intervention （PCI）-related myocardial injury remains controversial. In this prospective, single-center and double-blind study, we aimed to determine the diagnostic and prognostic value of cTnI as well as cTnT （cTns） in PCI-related myocardial injury in a Chinese population. A total of 1,008 patients with stable angina pectoris and non-ST-segment elevation acute coronary syndrome were recruited. The levels of cTnI and cTnT were examined before and after PCI. All patients were followed up for 26± 9 months to observe the incidence of major adverse cardiac events （MACEs）. Our results showed that post- PCI cTnI and/or cTnT levels were increased to more than the 99^th percentile upper reference limit （URL） in 133 （13.2%） patients, among which 22 （2.2%） were more than 5 × 99^th percentile URL. By univariate analysis, an elevation in cTns after PCI was not an independent predictor of increased MACEs, HR 1.35 （P = 0.33, 95% CI： 0.74-2.46）. In conclusion, our data demonstrate that the incidence of PCI-related myocardial injury is not common in a Chinese population and minor elevated cTns levels may not be a sensitive prognostic marker for MACEs.
基金financially supported by a project grant of the key faculty of Medical Renaissance program of Jiangsu Province,National Basic Research Program(973 program,2008CB517303)
文摘Objective：To investigate the effect of cardiomyocyte proliferation induced by human hepatocyte growth factor（HGF）in pigs with chronic myocardial infarction（CMI）.Methods：A steerable,deflectable 7F catheter incorporating a 27-guage needle was advanced percutaneously to the left ventricular myocardium of 18 pigs with CMI.Pigs were randomized（1：1：1）to receive adenoviral vector HGF（total dose,1×10^10 genome copies）,which was administered as five injections into the infarcted myocardium（total,1.0 mL）,or saline,or Ad-null（control groups）.Injections were guided by Ensite NavX left ventricular electroanatomical mapping.HGF and cyclin proteins were detected by western blot and immunoprecipitation analysis.Histological and immunohistochemical analysis determined proliferating cardiomyocytes.Myocardial perfusion and cardiac function were estimated by Gated-Single Photon Emission Computed Tomography（G-SPECT）.Results：Western blot analyses showed that HGF were predominantly expressed in the infarct core and border in the myocardium of the infarcted heart.G-SPECT analysis indicated that the HGF group had better cardiac function and myocardial perfusion four weeks after the injection of Ad-HGF than before the injection of Ad-HGF.After treatment there were more proliferating cardiomyocytes in the HGF group compared to either of the control groups.Furthermore,the HGF group myocardial samples expressed higher levels of p-Akt,cyclin A,cyclin E,cyclin D1,cdk2,cdk4 than those in the control groups.Conclusion：The over-expression of HGF activates pro-survival pathways,induces cardiomyocyte proliferation,and improves the perfusion and function of the porcine CMI heart.
基金supported by a grant from the Nature Science Foundation of the Education Department of Jiangsu Province(No.06kjb320006)
文摘Objective： Calcium-sensing receptors （CaSRs） are G-protein coupled receptors which maintain systemic calcium homeostasis and participate in hormone secretion, activation of ion channels, cell apoptosis, proliferation, and differentiation. Previous studies have shown that CaSRs induce apoptosis in isolated adult rat heart and in normal neonatal rat cardiomyocytes by G-protein-PLC-IP3 signaling transduction. However, little knowledge is presently available concerning the role of CaSRs in the apoptosis induced by ischemia and reperfusion in neonatal cardiomyocytes. Methods： Primary neonatal rat ventricular cardiomyocytes were incubated in ischemiamimetic solution for 2 h, and then re-incubated in normal culture medium for 24 h to establish a model of simu- lated ischemia/reperfusion （I/R）. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase- mediated dUTP nick end labeling （TUNEL）. The expression of CaSRs mRNA was detected by real-time reverse transcription polymerase chain reaction （RT-PCR）. In addition, the expressions of caspase-3 and Bcl-2 were analyzed by western blot. Results： The simulated I/R enhanced the expression of CaSRs and cardiomyocyte apoptosis. GdCl3, a specific activator of CaSRs, further increased the expression of CaSRs and cardiomyocyte apoptosis, along with up-regulation of caspase-3 and down-regulation of Bcl-2. Conclusion： CaSRs are associated with UR injury and apoptosis in neonatal rat ventricular cardiomyocytes via suppressing Bcl-2 and promoting caspase-3 expression.
基金supported by a grant from the National Natural ScienceFoundation of China(No.81270255)
文摘We report a case of a 49-year-old man who was admitted with a 3-hour history of sudden onset of substemal chest pain. Coronary angiography revealed that the left circumflex artery （LCX） was acutely and totally occluded at the mid-portion. In addition, the proximal and mid-portion of the right coronary artery （RCA） had a 60% occlusion. We inferred that the LCX was the culprit artery and primary PCI was successfully performed. Six weeks later, the patient had an eventful course with recurrence of chest pain. Coronary angiography showed no significant ste- nosis in the previous LCX lesion, while the proximal and middle potion of the RCA had a 90% occlusion. Our case demonstrates the systemic nature of acute coronary syndromes and highlights the inherent instability of coronary artery disease.
基金support by grants from the National Key TechnologiesR&D Program of China during the 11th Five-Year Plan Period(2007BAI07A10)the Jiangsu Province Science and TechnologySupport Program(BE2009613)the 9th Six Talents Peak Project ofJiangsu Province(WS-022),and the Qing Lan Project
文摘The purpose of this study was to assess the relationship between arterial stiffness, as measured by brachial-ankle pulse wave velocity （baPWV）, and the presence of the metabolic syndrome （MS） in a Chinese population. A total of 4,445 subjects were enrolled. The prevalence of MS in for the general population, males and females, respectively. our study population was 21.7%, 17.2% and 25.6% With adjustments for age, gender, cigarette smoking, heart rate, total cholesterol, low-density lipoprotein （LDL） cholesterol, and the use of anti-hypertensive drug, the stepwise regression analysis showed that baPWV had a significant relationship with components of MS, including systolic blood pressure （P 〈 0.001）, diastolic blood pressure （P 〈 0.001）, glucose （P 〈 0.001）, highdensity lipoprotein （HDL） cholesterol （P = 0.04）, and triglycerides （P 〈 0.001）, but no relationship with waist circumference （P = 0.25）. With an increase in the number of the MS components, baPWV increased significantly both in women and men. This study indicated that the MS is indeed a risk factor for arterial stiffness. Monitoring of baPWV in patients with MS may help in identifying persons at high risk for cardiovascular disease.
文摘Objective： To evaluate the effect of transplanting bone marrow-derived mesenchymal stem cells （BM-MSCs） or adenovirus5- hepatocyte growth factor（Ad5-HGF） via non-infarct-related artery injection in swine myocardial infarction models. Methods：BMMSCs were obtained from swine bone marrow and expanded in vitro to a purity of 〉50%. A myocardial infarction（MI） was created by ligating the distal left anterior descending artery in swine. Either BM-MSCs （5 × 10^6/ml） or Ad5-HGF （4 × 10^9 pfu） were transfused via the right coronary artery （non-infarcted artery） four weeks after MI. Gate-controled cardiac perfusion imaging was performed at the end of four and seven weeks after LAD ligation, to evaluate heart function and cardiac perfusion. Morphologic and histologic characteristics of the hearts were also studied. Results： （1）The gate-controlled cardiac perfusion imaging showed that the improvement in LVEF was greater in both treatment groups than in control group at the 4^th weeks. （2）In both treatment groups, capillary density was significantly higher than that of control group（P 〈 0.05）. Conclusion ：BM-MSCs or Ad5-HGF transplantation via non-infarcted artery administration can stimulate angiogenesis and improve heart function, but there was no difference in therapeutic efficacy between BM-MSCs and Ad5-HGF.
基金This work was performed at the SSRF XIL beamline(BL08U1B)Financial support was provided by the National Key R&D Program of China(2017YFA0206001)+1 种基金the National Key Basic Research Program of the China Science and Technology Commission of Shanghai Municipality(17JC1400802)the National Natural Science Foundation of China(Nos.11775291,11875314).
文摘This paper introduces the recent progress in methodologies and their related applications based on the soft x-ray interference lithography beamline in the Shanghai synchrotron radiation facility.Dual-beam,multibeam interference lithography and Talbot lithography have been adopted as basic methods in the beamline.To improve the experimental performance,a precise real-time vibration evaluation system has been established;and the lithography stability has been greatly improved.In order to meet the demands for higher resolution and practical application,novel experimental methods have been developed,such as high-order diffraction interference exposure,high-aspect-ratio and large-area stitching exposure,and parallel direct writing achromatic Talbot lithography.As of now,a 25 nm half-pitch pattern has been obtained;and a cm2 exposure area has been achieved in practical samples.The above methods have been applied to extreme ultraviolet photoresist evaluation,photonic crystal and surface plasmonic effect research,and so on.
文摘Dear Editor： Chronic total occlusions （CTOs） of the coronary artery are commonly encountered complex lesionst11. Percutaneous coronary intervention （PCI） for CTO is technically challenging due to low procedural success ratesTM. Microcatheter is one of the important devices for treatment of CTOTM. It has been widely used attributed to the excellent crossability whenever angula- tion and tortuousity of the coronary artery is encoun- tered. In the process, the microcatheter has to be withdrawn from the guide wire after the wire is proved to locate in the true lumen.
基金supported by grants from the Natural Science Foundation of Jiangsu Province (NoBK2007254)the National Natural Science Foundation of China (No 30871078)
文摘Objective： To investigate the role of glutathione S-transferase （GST） genetic variants and markers of oxidative stress and inflammation in smokingrelated coronary artery disease （CAD） patients. Methods： Five hundred and thirty-five Chinese CAD patients were successfully genotyped. Plasma total antioxidant status （TAOS）, glutathione, C-reactive protein （CRP）, fibrinogen（FIB） and white blood cell count （WBC） were determined to evaluate the oxidative stress and inflammatory response. Results： GSTM1-0/ GSTT1-0 subjects had a higher CRP, FIB, WBC and GSH and a lower TAOS compared to patients with wild-type GSTM1/GSTT1 genes, but there was significant difference only with regards to TAOS. Smokers with the null genotype of GSTT1 had the highest CRP and the lowest TAOS and GSH when compared to the GSTTI-1 genotype with smoking status, or the GSTT1-0 genotype with non-smoking status, or the GSTTI-I genotype with non-smoking status. However, we found no significant difference between these groups. Also, no significant interaction was observed between genotypes and smoking status in determining CRP levels. Conclusion： Our results suggest that GST polymorphisms do not modify the effect of smoking on markers of oxidative stress and inflammation in Chinese CAD patients.
基金supported by the National Key R&D Program of China(No.2017YFA0206001)the National Natural Science Foundation of China(Nos.11505275,51705369,11275255,11475251,and 11875314)the Shanghai Science and Technology Commission Research Projects(No.17JC1400802)
文摘Achromatic Talbot lithography(ATL)with high resolution has been demonstrated to be an excellent technique for large area periodic nano-fabrication.In this work,the uniformity of pattern distribution in ATL was studied in detail.Two ATL transmission masks with^50%duty cycle in a square lattice were illuminated by a spatial coherent broadband extreme ultraviolet beam with a relative bandwidth of 2.38%.Nonuniform dot size distribution was observed by experiments and finite-difference time-domain simulations.The sum of the two kinds of diffraction patterns,with different lattice directions(45°rotated)and different intensity distributions,results in the final nonuniform pattern distribution.
基金This study received support from the National Natural Science Foundations of China(No.81970302).
文摘Background and Aims:Unfractionated heparin(UFH)and bivalirudin are widely used as anticoagulants in cardiovascular medicine,including for thrombosis prevention during coronary angiography(CAG)and percutaneous coronary intervention(PCI).Little is known of the effects of UFH and bivalirudin on liver and kidney function in patients subjected to these procedures.This study compared the effects of bivalirudin and UFH on liver/renal function in patients with coronary artery disease who underwent CAG,with or without PCI.Methods:The study comprised 134 consecutive patients(40–89 years-old),who underwent CAG(or CAG and PCI);among them,66 and 68 patients were subject to,respectively,bivalirudin or UFH.The following indicators of liver/renal function were measured before and after the procedures:plasma alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen,estimated glomerular filtration rate(eGFR),creatinine clearance,and serum creatinine.Patients were further stratified by severity of chronic kidney disease(CKD),based on original eGFR.Results:Relative to baseline,in the bivalirudin group,ALT and AST were higher after CAG(p=0.005,0.025),while blood urea nitrogen and serum creatinine were lower(p=0.049,<0.001).In the UFH group,ALT,AST,eGFR,and creatinine clearance were lower after CAG(p≤0.001,all).Patients given bivalirudin with moderate or severe CKD,but not those with mild CKD,gained significant improvement in kidney function.Conclusions:Relative to UFH,bivalirudin may better safeguard the renal function of patients with coronary artery disease who undergo CAG,especially patients with moderate-to-severe renal insufficiency.UFH may cause less liver damage than bivalirudin.
基金Supported by the Key Project of the National Natural Science Foundation of China (Grant No. 20737001)the National Natural Science Foundation Key Project of China (Grant No. 20737001)the Science and Technology Development Founda-tion Project of Nanjing Medical University (Grant No. 06NMUM021)
文摘Polybrominated diphenyl ether congeners (PBDEs) might activate the AhR (aromatic hydrocarbon receptor) signal transduction, and thus might have an adverse effect on the health of humans and wildlife. Because of the limited experimental data, it is important and necessary to develop structure-based models for prediction of the toxicity of the compounds. In this study, a new molecular structure representation, molecular hologram, was employed to investigate the quantitative relationship between toxicity and molecular structures for 18 PBDEs. The model with the significant correlation and robustness (r <sup>2</sup> = 0.991, q <sup>2</sup> <sub>LOO</sub> = 0.917) was developed. To verify the robustness and prediction capacity of the derived model, 14 PBDEs were randomly selected from the database as the training set, while the rest were used as the test set. The results generated under the same modeling conditions as the optimal model are as follows: r <sup>2</sup> = 0.988, q <sup>2</sup> <sub>LOO</sub> = 0.598, r <sup>2</sup> <sub>pred</sub> = 0.955, and RMSE (root-mean-square of errors) = 0.155, suggesting the excellent ability of the derived model to predict the toxicity of PBDEs. Furthermore, the structural features and molecular mechanism related to the toxicity of PBDEs were explored using HQSAR color coding.
基金Supported by the National Natural Science Foundation of China(Grant Nos. 20777035 & 20737001) 863 Advanced Research Project (Grant Nos. 2007AA06Z416, 2006AA06Z424 & 2007AA06A405)
文摘Endocrine disrupting chemicals (EDCs) in the natural environment exhibit a unique non-monotonic dose-response curve and it is impossible to select one simple index to characterize the bilogogical activity of these compounds. Quantitative structure-activity relationship (QSAR) study on non-monotonic dose-response curve has become a real challenge presently. In order to explore the possible mechanism for the non-monotonic dose-response curve of polychlorinated biphenyls congeners (PCBs) in chicken embryo hepatocyte bioassay, AM1 method of ChemOffice was adopted to calculate necessary structure descriptors for PCBs, while the interactions between PCBs and simulated AhR ligand binding domain (LBD) were analyzed by using FlexX in SYBYL7.0. Different binding modes for PCBs have been distinguished not only from aligned conformation but also from free binding energy. Some QSAR models were established separately for both low and high doses ranges, revealing that receptor binding may predominate in the interference of the physiological function of cytochrome P4501A-P4501A in the low doses range. But with the higher doses range, the EROD suppression might be related to acute toxicity owing to molecular polarity or distribution of charges and consequently damage structure and function of chicken embryo hepatocyte.
基金National Natural Science Foundation of China (Nos. 81770361& 82070367)。
文摘Cardiovascular disease(CVD)remains the leading cause of death worldwide.Therefore,exploring the mechanism of CVDs and critical regulatory factors is of great significance for promoting heart repair,reversing cardiac remodeling,and reducing adverse cardiovascular events.Recently,significant progress has been made in understanding the function of protein kinases and their interactions with other regulatory proteins in myocardial biology.Protein kinases are positioned as critical regulators at the intersection of multiple signals and coordinate nearly every aspect of myocardial responses,regulating contractility,metabolism,transcription,and cellular death.Equally,reconstructing the disrupted protein kinases regulatory network will help reverse pathological progress and stimulate cardiac repair.This review summarizes recent researches concerning the function of protein kinases in CVDs,discusses their promising clinical applications,and explores potential targets for future treatments.
