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Protective Effect of Hydroxysafflor Yellow A on Bleomycin-Induced Pulmonary Inflammation and Fibrosis in Rats

Chinese Journal of Integrative Medicine 2018年第1期24卷 32-39页

作者： JIN Ming WANG Lin WU Yan ZANG Bao-xia TAN Li Department of Pharmacology Beijing Institute of Heart Lung and Blood Vessel Diseases Beijing Anzhen HospitalCapital Medical University

Objective： To observe the effect of hydroxysafflor yellow A （HSYA）, an active ingredient of a traditional Chinese herbal medicine Carthamus tinctorius L., on lung inflammation and pulmonary fibrosis induced by bleomycin （BLM） in rats. Methods： Animals were divided into 6 groups including normal group, model group, three HSYA groups and dexamethasone （DXM） group. Three doses of HSYA （35.6, 53.3, and 80.0 mg？kg–1？day–1） were intraperitoneally （i.p.） injected in rats for 3 weeks after BLM administration and DXM was used as the positive control （n=8 or 12）. Arterial blood gas was assayed and morphological changes were observed. lung mRNA expressions of tumor necrosis factor （TNF）-α, interleukin （IL）-1β, IL-6 and some cytokines in lung tissue were detected by real-time polymerase chain reaction. Nuclear factor-κB p65 or α-smooth muscle actin （α-SMA） protein distribution in rat lung tissue was observed by immunohistochemistry. Results： On the 7th day after BLM administration, lung tissue showed serious inflammation. Treatment with HSYA or DXM ameliorated lung inflammation. After treatment with HSYA or DXM, oxygen partial pressure （PaO2） increased （HSYA 80.0 mg？kg–1, P〈0.01） and CO2 partial pressure （PaCO2） decreased （HSYA 53.3, 80.0 mg？kg–1, P〈0.05）. Moreover, the mRNA expression of TNF-α, IL-1β, and IL-6; and the number of NF-κB p65 positive cells was lower in HSYA 53.3 and 80.0 mg？kg–1 groups than those in the model group （all P〈0.05）. Twenty-one days after BLM administration, HSYA or DXM treatment ameliorated fibrosis, increased PaO2 （HSYA 53.3, 80.0 mg？kg–1, P〈0.01）, and decreased PaCO2 （53.3 and 80.0 mg？kg–1, P〈0.05）. Further, the mRNA expression of TGF-β1, α-SMA, and collagen Ⅰ as well as the number of α-SMA positive cells increased in the model group and HSYA can attenuate these changes （53.3, 80.0 mg？kg–1, P〈0.05）. Hematoxylin and eosin and Masson＇s trichrome staining indicated that the fibrosis and collagen deposition were ameliorated in HSYA groups （53.3, 80.0 m

关键词： hydroxysafflor yellow A pulmonary fibrosis pulmonary inflammation nuclear factor- K B p65,α-smooth muscle actin Chinese medicine

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Immobilization of insulin-like growth factor-1 onto thermosensitive hydrogels to enhance cardiac progenitor cell survival and differentiation under ischemic conditions

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Science China Chemistry 2014年第4期57卷 568-578页

作者： LI ZhenQing XU YanYi LI HaiChang GUAN JianJun Department of Materials Science and Engineering The Ohio State University Davis heart and lung Research Institute The Ohio State University

Stem cell therapy is a promising approach to treat myocardial infarction. However, direct delivery of stem cells into hearts experiences poor cell engraftment and differentiation, due to ischemic conditions （low nutrient and oxygen） in the infarct hearts. Development of suitable cell carriers capable of supporting cell survival and differentiation under these harsh conditions is critical for improving the efficacy of current stem cell therapy. In this work, we created a family of novel cell carriers based on thermosensitive hydrogels and insulin-like growth factor 1 （IGF-1）, and investigated if these cell carriers can improve cell sur- vival and differentiation under ischemic conditions. The thermosensitive hydrogels were synthesized from N-isopropylacryla- mide, acrylic acid, acrylic acid N-bydroxysuccinicimide ester, and 2-hydroxyethyl methacrylate-oligo（hydroxybutyrate）. The hydrogel solutions can be readily injected through 26G needles, and can quickly solidify at 37 ~C to form highly flexible hy- drogels. IGF-I was immobilized into the hydrogels in order to support long-term cell survival and differentiation. Different amount of IGF- 1 was immobilized by using hydrogels with different content of N-hydroxysuccinicimide ester groups. Cardio- sphere derived cells were encapsulated in the hydrogels and cultured under ischemic conditions. The results demonstrated that a significant improvement of cell survival and differentiation was achieved after IGF-1 immobilization. These IGF-1 immobi- lized hydrogels have the potential to improve cell survival and differentiation in infarct hearts.

关键词： thermosensitive hydrogels cardiosphere derived cells myocardial infarction cardiac differentiation stem cells

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BMPR2 spruces up the endothelium n pulmonary hypertension

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Protein & Cell 2015年第10期6卷 703-708页

作者： Jianhua Xiong Center for Molecular Medicine National Heart Lung and Blood Institute National Institutes of Health Bethesda MD 20892USA

Pulmonary hypertension （PH） is a potentially lethal disorder because of a dearth of effective therapeutic options （Schermuly et al., 2011; Mehari et al., 2014）. Pulmonary arterial hypertension （PAH） is a major type of PH that is defined by a mean pulmonary arterial pressure higher than 25 mm Hg at rest or 30 mm Hg during exercise （Kovacs et al., 2009）.

关键词： endothelium pulmonary hypertension

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Obstructive sleep apnea is associated with severity and long-term prognosis of acute coronary syndrome

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Journal of Geriatric Cardiology 2018年第2期15卷 146-152页

作者： Shuo JIA Yu-Jie ZHOU Yi YU Si-Jing WU Yan SUN Zhi-Jian WANG Xiao-Li LIU Bright Eric King Ying-Xin ZHAO Dong-Mei SHI Yu-Yang LIU Zhi-Ming ZHOU Bejing Anzhen Hospital Capital Medical University Beijing Institute of Heart Lung and Blood Vessel Disease Beijing China

Background Obstructive sleep apnea （OSA） is a common disease in patients with acute coronary syndrome （ACS） and associated with an increased risk of fatal and nonfatal cardiovascular events. However, most patients in previous study were treated with bare metal stents and the sample sizes were relatively low. The goal of this study was to evaluate the influence of OSA on the severity and prognosis of patients admitted for ACS. Methods In this prospective cohort study, we enrolled patients with ACS who were hospitalized for coronary angiogram/percutaneous coronary intervention and undergone polysomnography. We divided the patients into two groups： moderate to severe OSA group [apnea-hypopnea index （AHI）〉 15 events/h] and control group （AHI ≤ 15 events/h）. They were followed up for up 32 months. Then, we compared the ACS severity and long-term major adverse cardiovascular events （MACE） in patients with different severity of OSA. Results Five hundred and twenty nine patients were included in the final analysis, with 76% of them being men and an average age of 59 ＋ 10 years. The overall mean AHI is 29 ± 19 events/h, 70.5% of them （373/529） being with moderate to severe OSA and 29.5% （156/529） assign into control group. Compared with controls, patients with moderate or severe OSA exhibited a higher prevalence of hypertension as well as higher body mass index, SYNTAX score, Epworth score and length of hospitalization. With a median follow-up duration of 30 months, accumulative rate of MACE was also higher in patients with moderate or severe OSA than that in the control group （8.6% vs. 3.2%, P = 0.028）. After adjusting for baseline confounders by cox regression model, moderate to severe OSA was an independent risk factor of long-term MACE （P = 0.047, HR = 1.618, 95% CI： 1.069-3.869）. Conclusions The results of this study demonstrate that moderate or severe OSA is correlated with disease severity and associated with worse long-term prognosis in ACS patients. The results rai

关键词： Coronary angiogram Coronary artery disease Obstructive sleep apnea Outcomes

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Comparison of very-high-frequency ultrasound assessment of radial arterial wall layers after first and repeated transradial coronary procedures

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Journal of Geriatric Cardiology 2017年第4期14卷 245-253页

作者： Bei-Bei ZHANG Yu-Jie ZHOU Jie DU Shi-Wei YANG Zhi-Jiang WANG Hua SHEN Zhi-Ming ZHOU Bering Anzhen Hospital Capital Medical University Beijing Institute of Heart Lung and Blood Vessel Disease Beijing China

Background Transradial coronary procedure （TRP） traumatizes the radial artery （RA）, especially resulting in changes to arterial wall morphology. This study explored the significance of the early onset of traumatic effects to wall layers of the RA following the first TRP （FTRP） and repeat TRP （RTRP） using very-high-frequency ultrabiomicroscopy （VHFUBM）. Methods A total of 1431 patients that re- ceived TRP were divided into the FTRP group that comprised 781 patients and the RTRP group that comprised 650 patients depending on the number of procedures. Two-dimensional RA images were acquired by 30-55 MHz ultrasound one day before and one day after the pro- cedure. Results After TRP, the incidence of intimal tears, medial dissections and external elastic lamina fracture were greater in the RTRP （P 〈 0.001）. The RTRP group showed significantly thicker intimal thickness （IT）, media thickness （MT）, adventitia thickness and all complex layer thicknesses as compared with the FTRP group （P 〈 0.001）. Conclusions Multivariate linear regression analysis discovered that repeated TRP and other observations were independent predictors of increased IT in post-operative RA. VHFUBM provides an approach to study structural and histopathological injury in the wall layers of RA which showed increased trauma to the RA following RTRP.

关键词： Radial arterial wall morphology Transradial procedure Very-high-frequency ultrabiomicroscopy

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Optimal timing of staged percutaneous coronary intervention in ST-segment elevation myocardial infarction patients with multivessel disease

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Journal of Geriatric Cardiology 2018年第5期15卷 356-362页

作者： Xue-Dong ZHAO Guan-Qi ZHAO Xiao WANG Shu-Tian SHI Wen ZHENG Rui-Feng GUO Shao-Ping NIE Beijing Anzhen Hospital Capital Medical University Beijing Institute of Heart Lung and Blood Vessel Diseases Beijing China

Background Studies have shown that staged percutaneous coronary intervention （PCI） for non-culprit lesions is beneficial for prog- nosis of ST-segment elevation myocardial infarction （STEMI） patients with multivessel disease. However, the optimal timing of staged re- vascularization is still controversial. This study aimed to find the optimal timing of staged revascularization. Methods A total of 428 STEMI patients with multivessel disease who underwent primary PCI and staged PCI were included. According to the time interval between primary and staged PCI, patients were divided into three groups （〈 1 week, 1- weeks, and 2-12 weeks after primary PCI）. The primary endpoint was major adverse cardiovascular events （MACE）, a composite of all-cause death, non-fatal re-infarction, repeat revascularization, and stroke. Cox regression model was used to assess the association between staged PCI timing and risk of MACE. Results During the follow-up, 119 participants had MACEs. There was statistical difference in MACE incidence among the three groups （〈 1 week： 23.0%; 1-2 weeks： 33.0%; 2-12 weeks： 40.0%; P = 0.001）. In the multivariable adjustment model, the timing interval of staged PCI ≤ 1 week and l-2 weeks were both significantly associated with a lower risk of MACE [hazard ratio （HR）： 0.40, 95% confidence intervals （CI）： 0.24-4）.65; HR： 0.54, 95% CI： 0.3 lq3.93, respectively], mainly attributed to a lower risk of repeat revascularization （HR： 0.41, 95% CI： 0.24-0.70; HR： 0.36, 95% CI： 0.18-0.7）, compared with a strategy of 2-12 weeks later of primary PCI. Conclusions The optimal timing of staged PCI for non-culprit vessels should be within two weeks after primary PCI for STEMI patients.

关键词： Myocardial infarction Multivessel disease Non-culprit lesion Percutaneous coronary intervention Timing

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Role of coronary physiology in the contemporary management of coronary artery disease

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World Journal of Clinical Cases 2015年第2期3卷 148-155页

作者： Neil Ruparelia Rajesh K Kharbanda Oxford heart centre John Radcliffe Hospital

Coronary artery disease(CAD) remains the leading cause of death worldwide with approximately 1 in 30 patients with stable CAD experiencing death or acute myocardial infarction each year. The presence and extent of resultant myocardial ischaemia has been shown to confer an increased risk of adverse outcomes. Whilst, optimal medical therapy(OMT) forms the cornerstone of the management of patients with stable CAD, a significant number of patients present with ischaemia refractory to OMT. Historically coronary angiography alone has been used to determine coronary lesion severity in both stable and acute settings. It is increasingly clear that this approach fails to accurately identify the haemodynamic significance of lesions; especially those that are visually "intermediate" in severity. Revascularisation based upon angiographic appearances alone may not reduce coronary events above OMT. Technological advances have enabled the measurement of physiological indices including the fractional flow reserve, the index of microcirculatory resistance and the coronary flow reserve. The integration of these parameters into the routine management of patients presenting to the cardiac catheterization laboratory with CAD represents a critical adjunctive tool in the optimal management of these patients by identifying patients that would most benefit from revascularisation and importantly also highlighting patients that would not gain benefit and therefore reducing the likelihood of adverse outcomes associated with coronary revascularisation. Furthermore, these techniques are applicable to a broad range of patients including those with left main stem disease, proximal coronary disease, diabetes mellitus, previous percutaneous coronary intervention and with previous coronary artery bypass grafting. This review will discuss current concepts relevant to coronary physiology assessment, its role in the management of both stable and acute patients and future applications.

关键词： Ischaemia Coronary physiology Coronary flow reserve Fractional flow reserve Coronary artery disease

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To be EndMT or not to be, that is the question in pulmonary hypertension

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Protein & Cell 2015年第8期6卷 547-550页

作者： Jianhua Xiong Center for Molecular Medicine National Heart Lung and Blood Institute National Institutes of Health Bethesda MD 20892 USA

Pulmonary hypertension （PH） is a progressive and devas- tating disease of various causes that is associated with structural and functional disorder and inappropriately increased pressure of pulmonary small- to medium-sized vasculature. Extensive pulmonary vascular remodeling with narrowing lumen is well characterized in all forms of PH, which is hemodynamically defined by a mean pulmonary artery pressure exceeding 25 mmHg at rest （Schermuly et al., 2011; Mehari et al., 2014）. The morbidity and mortality of PH continues to increase due to no cure （Mehari et al., 2014）; however, our understanding of the mechanism and therapeutics underlying PH remains far from complete. There are many competing hypotheses for how PH develops in a genetic or sporadic way （Schermuly et al., 2011 ）.

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Comparison of His-purkinje bundle pacing and right ventricular inflow tract septal pacing in the elderly

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Journal of Geriatric Cardiology 2020年第6期17卷 351-358页

作者： Chun-Shan LU Wen-Long DAI Dong-Ping FANG Peng HAO Dong-Fang HE Qiao-Yuan LI Xu LIU Can-Can LIN Cheng-Jun GUO Department of Cardiology Beijing Anzhen HospitalCapital Medical UniversityBeijing Institute of HeartLung and Blood Vessel DiseasesBeijingChina

Objective To compare the short-term clinical effect and electrical parameters of His-purkinje bundle pacing(HPBP) and right ventricular inflow tract septal pacing(RVIP) in the elderly. Methods Between April 2017 and September 2019, sixty patients with indications for permanent cardiac pacing and resynchronization therapy in Beijing Anzhen Hospital were divided into the HPBP and RVIP groups, and were analyzed. A ventricular pacing lead was implanted in left ventricular septal sites with left bundle potentials or His potentials in the HPBP group. The lead was placed in right ventricular inflow tract septal sites close to distal His-bundle regions without potentials from the His-purkinje conduction system in the RVIP group. Lead impedance, R wave amplitude, pacing thresholds, QRS duration, left ventricular ejection fraction(LVEF), and left ventricular end-diastolic diameter(LVEDD), mitral regurgitation area reflux, QTc, T wave directivity, Tp-e and Tp-e/QT ratio were compared between the HPBP and RVIP groups during the procedure and the short-month follow-up. Results No significant differences were found in lead impedance, R wave amplitude, QRS duration, LVEF, LVEDD, mitral regurgitation area reflux, QTc, T wave directivity, Tp-e and Tp-e/QT ratio between the HPBP and RVIP groups. However, the pacing threshold was significantly lower in the HPBP group than in the RVIP group(0.7 ± 0.2 vs. 0.9 ± 0.3 V, P = 0.02). Conclusions The efficacy and electrical parameters of HPBP is comparable with RVIP during the procedure and the short-term follow-up.

关键词： Bundle branch block His-purkinje bundle pacing Pacemaker Right ventricular inflow tract

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Delayed xenon post-conditioning mitigates spinal cord ischemia/reperfusion injury in rabbits by regulating microglial activation and inflammatory factors

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Neural Regeneration Research 2018年第3期13卷 510-517页

作者： Yan-wei Yang Yun-lu Wang Jia-kai Lu Lei Tian Mu Jin Wei-ping Cheng Department of Anesthesiology Beijing Anzhen Hospital Capital Medical University Beijing Institute of Heart Lung and Blood Vessel Diseases Beijing China

The neuroprotective effect against spinal cord ischemia/reperfusion injury in rats exerted by delayed xenon post-conditioning is stronger than that produced by immediate xenon post-conditioning. However, the mechanisms underlying this process remain unclear. Activated microglia are the main inflammatory cell type in the nervous system. The release of pro-inflammatory factors following microglial activation can lead to spinal cord damage, and inhibition of microglial activation can relieve spinal cord ischemia/reperfusion injury. To investigate how xenon regulates microglial activation and the release of inflammatory factors, a rabbit model of spinal cord ischemia/reperfusion injury was induced by balloon occlusion of the infrarenal aorta. After establishment of the model, two interventions were given：（1） immediate xenon post-conditioning—after reperfusion, inhalation of 50% xenon for 1 hour, 50% N2/50%O2 for 2 hours; （2） delayed xenon post-conditioning—after reperfusion, inhalation of 50% N2/50%O2 for 2 hours, 50% xenon for 1 hour. At 4, 8, 24, 48 and 72 hours after reperfusion, hindlimb locomotor function was scored using the Jacobs locomotor scale. At 72 hours after reperfusion, interleukin 6 and interleukin 10 levels in the spinal cord of each group were measured using western blot assays. Iba1 levels were determined using immunohistochemistry and a western blot assay. The number of normal neurons at the injury site was quantified using hematoxylin-eosin staining. At 72 hours after reperfusion, delayed xenon post-conditioning remarkably enhanced hindlimb motor function, increased the number of normal neurons at the injury site, decreased Iba1 levels, and inhibited interleukin-6 and interleukin-10 levels in the spinal *** xenon post-conditioning did not noticeably affect the above-mentioned indexes. These findings indicate that delayed xenon post-conditioning after spinal cord injury improves the recovery of neurological function by reducing microglial

关键词： nerve regeneration spinal cord injury xenon immediate post-conditioning delayed post-conditioning ischemia/reperfusion microglia interleukin-6 interleukin-10 ionized calcium binding adaptor molecule 1 inflammatory reaction neural regeneration

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