Age-specific differences in non-cardiac comorbidities among elderly patients hospitalized with heart failure: a special focus on young-old, old-old, and oldest-old

Background:Despite the growing epidemic of heart failure(HF),there is limited data available to systematically compare noncardiac comorbidities in the young-old,old-old,and oldest-old patients hospitalized for HF.The precise differences will add valuable information for better management of HF in elderly patients.Methods:A total of 1053 patients aged 65 years or older hospitalized with HF were included in this study.Patients were compared among three age groups:(1)young-old:65 to 74 years,(2)old-old:75 to 84 years,and(3)oldest-old:≥85 years.Clinical details of presentation,comorbidities,and prescribed medications were recorded.Results:The mean age was 76.7 years and 12.7%were 85 years or older.Most elderly patients with HF(97.5%)had at least one of the non-cardiac comorbidities.The patterns of common non-cardiac comorbidities were different between the young-old and oldestold group.The three most common non-cardiac comorbidities were anemia(53.6%),hyperlipidemia(45.9%),and diabetes(42.4%)in the young-old group,while anemia(73.1%),infection(58.2%),and chronic kidney disease(44.0%)in the oldest-old group.Polypharmacy was observed in 93.0%elderly patients with HF.Additionally,29.2%patients were diagnosed with infection,and 67.0%patients were prescribed antibiotics.However,60.4%patients were diagnosed with anemia with only 8.9%of them receiving iron repletion.Conclusions:Non-cardiac comorbidities are nearly universal in three groups but obviously differ by age,and inappropriate medications are very common in elderly patients with HF.Further treatment strategies should be focused on providing optimal medications for age-specific non-cardiac conditions.

Serum uric acid in patients with acute ST-elevation myocardial infarction

BACKGROUND:Few studies investigated serum uric acid levels in patients with acute STelevation myocardial infarction(STEMI).The study was to assess the clinical value of serum uric acid levels in patients with acute ST-elevation myocardial infarction(STEMI).METHODS:Totally 502 consecutive patients with STEMI were retrospectively studied from January 2005 to December 2010.The level of serum lipid,echocardiographic data and in-hospital major adverse cardiovascular events(MACE) in patients with hyperuricemia(n=119) were compared with those in patients without hyperuricemia(n=383).The relationship between the level of serum uric acid and the degree of diseased coronary artery was analyzed.All data were analyzed with SPSS version 17.0 software for Student's t test,the Chi-square test and Pearson's correlation coefficient analysis.RESULTS:Serum uric acid level was positively correlated with serum triglyceride level.Hyperlipidemia was more common in hyperuricemia patients than in non-hyperuricemia patients(43.7%vs.33.7%,P=0.047),and serum triglyceride level was significantly higher in hyperuricemia patients(2.11±1.24 vs.1.78±1.38,P=0.014).But no significant association was observed between serum uric acid level and one or more diseased vessels(P>0.05).Left ventricular end-diastolic diameter(LVEDd) was larger in hyperuricemia patients than in non-hyperuricemia patients(53.52±6.19 vs.52.18±4.89,P=0.041).The higher rate of left systolic dysfunction and diastolic dysfunction was discovered in hyperuricemia patients(36.4%vs.15.1%,P<0.001;68.2%vs.55.8%,P=0.023).Also,hyperuricemia patients were more likely to have in-hospital MACE(P<0.05).CONCLUSIONS:Serum uric acid level is positively correlated with serum triglyceride level,but not with the severity of coronary artery disease.Hyperuricemia patients with STEMI tend to have a higher rate of left systolic dysfunction and diastolic dysfunction and more likely to have more in-hospital MACE.

Association of urotensin Ⅱ with angiographic severity of coronary artery disease

Objective The goal of this study was to examine the association between urotensin Ⅱ (U Ⅱ) concentration and the severity of coronary artery disease (CAD). Methods We studied U Ⅱ concentrations in 100 patients with known or suspected CAD referred for cardiac catheterization. Based on coronary angiograms, subjects were classified as having no or mild CAD (stenosis <50%) and significant CAD (stenosis=50%). Micheal score system was used to estimate the severity of CAD. Result U Ⅱ concentration in the significant CAD group had no difference compared with the no or mild CAD group (1.95±1.18pmol/L vs 2.04±1.47pmol/L, P>0.05), but higher in the severe group (score =9) than in the normal or nearly normal group (score<3)(2.50±1.62pmol/L vs 1.61±1.05pmol/L, P=0.03). UⅡ concentration had no relationship with other known risk factors, but it correlated with CAD severity (r=0.213, P=0.034). In multiple regression analysis, U Ⅱ is one of the determinants of the severity of CAD, other than age, abnormal glucose, hypertension and gender. Conclusios U Ⅱ is elevated in severe CAD and there is a significant relationship between U Ⅱ concentration and CAD severity. (J Geriatr Cardiol 2007;4:229-232.)

Significance of Normal Range Urinary Albumin to Creatinine Ratio in Chinese Subjects with Metabolic Syndrome

Summary： This study was aimed to investigate clinical features of Chinese metabolic syndrome （MS） subjects with normal urinary albumin to creatinine ratio （UACR） and to estimate independent correla- tion factor for UACR. Data were drawn from a cross-sectional survey in participants having MS. The patients with different grade of albuminuria were divided into 4 groups according to the value of UACR （〈10, 10-20, 21-30, 〉30 mg/g）. All underwent biochemical tests. Bioelectrical impedance body fat content, islet [3-cell function and insulin sensitivity were measured. Multivariable linear regression mod- els were applied to further determine association between UACR and clinical factors with adjustment. Systolic blood pressure （SBP）, diastolic blood pressure （DBP）, mean arterial pressure （MAP）, fasting plasma glucose （FPG）, glycosylated hemoglobin （HbAlc）, TG, fat mass, fat content and homeostasis model assessment for insulin resistance （HOMA-IR） were significantly higher in the group with UACR at 10-20 mg/g than those in the group with UACA lower than 10 mg/g （P〈0.05）. Multivariable linear regression showed that TG, HbAlc, waist-hip ratio （WHR） and SBP were independently associated with UACR. The patients with normal UACR had abnormal levels of MS components. The factors in- dependently associated with UACR were TG, HbAlc, WHR and SBP.

Real world effectiveness of PCSK-9 inhibitors combined with statins versus statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease in China(RWE-PCSK study)

BACKGROUND The efficacy and safety of proprotein convertase subtilisin/kexin type 9(PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease(ASCVD).METHODS This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention(PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events(MACE) over six months were compared between two groups.A propensity score-matched(PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE.RESULTS In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol(LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81%(P < 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group(P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE(hazard ratio = 2.52, 95% CI: 0.49-12.97, P = 0.250).CONCLUSIONS In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study.

Tanshinone IA decreases microcalcifications in plaque via Nox1-dependent reactive oxygen species generation of smooth muscle cells in apoE^(-/-) mice

A variety of NADPH oxidase(Nox)isoforms including Noxs 1,2,4 and 5 catalyze the formation of reactive oxygen species(ROS)in the vascular wall.The Noxl isoform complex in smooth muscle cells has received greater attention in the progression of atherogenesis in animal models.Thus,we explored the effect of traditional Chinese herbal medicine monomer tanshinone IIA on microcalcifications,and investigated the underlying molecular mechanism of ROS.The 8-week old maleapolipoprotein E-deficient(ApoE^(-/-))mice and C57BL/6 mice were divided into three groups:Control group(C57BL/6 mice),Model group(ApoE^(-/-) mice).

Cardioprotective effect of liposomal prostaglandin E1 on a porcine model of myocardial infarction reperfusion no-reflow

Objective:To evaluate whether liposomal prostaglandin E1 (lipo-PGE1) can decrease reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction (AMI).Methods:Twenty-two male Chinese mini-swines were randomized into three groups:six in a sham-operation group,and eight each in the control and lipo-PGE1 groups.The distal part of the left anterior descending coronary artery (LAD) in the latter two groups was completely occluded for 2 h,and then reperfused for 3 h.Lipo-PGE1 (1 μg/kg) was injected 10 min before LAD occlusion until reperfusion for 1 h in the lipo-PGE1 group.Hemodynamic data and proinflammatory cytokines were examined before AMI,2 h after occlusion,and 1,2,and 3 h after reperfusion.Myocardial contrast echocardiography (MCE) and double staining were performed to evaluate the myocardial no-reflow area (NRA).Results:Left ventricular systolic pressure and end-diastolic pressure significantly improved in the lipo-PGE1 group after reperfusion compared with the control group and also 2 h after AMI (P<0.05 for both).MCE and double staining both showed that lipo-PGE1 decreased reperfusion NRA after AMI (P<0.05,P<0.01).Lipo-PGE1 decreased serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) after myocardial infarction reperfusion (P<0.05 for both).Conclusions:Lipo-PGE1 is cardioprotective in our porcine model of myocardial infarction reperfusion no-reflow,decreasing NRA and attenuating the inflammatory response.

Asymmetric Dimethylarginine Predicts One-year Recurrent Cardiovascular Events: Potential Biomarker of "Toxin Syndrome" in Coronary Heart Disease

Objective: To examine the prognostic value of serum levels of asymmetric dimethylarginine(ADMA)in patients with stable coronary heart disease(CHD) thus explore a potential biomarker of "toxin syndrome" in CHD.Methods: In this prospective nested case-control study, 36 of 1,503 Chinese patients with stable CHD experienced at least 1 recurrent cardiovascular event(RCE) during 1-year fol ow-up. Serum levels of ADMA at the start of fol ow-up were compared between these 36 cases and 36 controls which matched to cases in terms of gender, age, history of hypertension, and myocardial infarction. Results: Based on the crude model, subjects in the 2 highest ADMA quartiles showed signi?cantly higher risk of developing RCE than those in the lowest ADMA quartile [odds ratio(OR) 4.09, 95%confidence interval(CI) 1.01 to 16.58; OR 6.76, 95% CI 1.57 to 29.07]. This association was also observed in the case-mix model(OR 5.51, 95% CI 1.23 to 24.61; OR 7.83, 95% CI 1.68 to 36.41) and multivariable model(OR 6.64,95% CI 1.40 to 31.49; OR 13.14, 95% CI 2.28 to 75.71) after adjusting for confounders. The multivariable model which combined ADMA and high-sensitivity C-reactive protein(hs CRP) showed better predictive power with areas under the receiver operator characteristic curves(0.779) than the model of either ADMA(0.694) or hs CRP(0.636). Conclusion:Serum ADMA level may be a potential biomarker of "toxin syndrome" in CHD which shows favorable prognostic value in predicting 1-year RCE in patients with stable CHD. [The registration number is Chi CTR-PRNRC-07000012]

The Preventive Effect of Garlicin on A Porcine Model of Myocardial Infarction Reperfusion No-reflow

Objective： To evaluate whether garlicin can prevent reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction （AMI）. Methods： Twenty-two male Chinese mini swines were randomized into 3 groups： sham-operation group （n=6）, control group （n=8）, and garlicin group （n=8）. The distal part of left anterior descending coronary artery （LAD） in swines of the latter two groups was completely occluded by dilated balloon for 2 h and a successful AMI model was confirmed by coronary angiography （CAG） and electrocardiograph （ECG）, which was then reperfused for 3 h. In the sham-operation group, balloon was placed in LAD without dilatation. Garlicin at a dosage of 1.88 mg/kg was injected 10 min before LAD occlusion until reperfusion for 1 h in the garlicin group. To assess serial cardiac function, hemodynamic data were examined by catheter method before AMI, 2 h after occlusion and 1, 2, and 3 h after reperfusion. Myocardial contrast echocardiography （MCE） and double staining with Evans blue and thioflavin-S were performed to evaluate myocardial no-reflow area （NRA） and risk area （RA）. Results： Left ventricular systolic pressure and left ventricular end-diastolic pressure significantly improved in the garlicin group after reperfusion compared with the control group （P〈0.05） and 2 h after AMI （P〈0.05）. MCE showed garlicin decreased reperfusion NRA after AMI compared with the control group （P〈0.05）. In double staining, NRNRA in the garlicin group was 18.78%, significantly lower than that of the control group （49.84%, P〈0.01）. Conclustions： Garlicin has a preventive effect on the porcine model of myocardial infarction reperfusion no-reflow by improving hemodynamics and decreasing NRA.

XS0601 REDUCES THE INCIDENCE OF RESTENOSIS: A PROSPECTIVE STUDY OF 335 PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION IN CHINA

Background XS0601, consisting of active ingredients （Chuangxiongol and paeoniflorin）, has been shown to inhibit arterial neointimal hyperplasia in animal models and in preliminary human studies. The objective of this study was to evaluate the safety and efficacy of XS0601 in preventing restenosis following percutaneous coronary intervention （PCI）. Methods A multi-center, randomized, double-blind, placebo-controlled trial was conducted. A total of 335 patients were randomized into treatment with the oral administration of XS0601, or a placebo for 6 months after successful PCI. Angiographic follow-up was scheduled at 6 months, and clinical follow-ups performed at 1, 3 and 6 months after PCI. The primary end point was angiographic restenosis. The secondary end points were the combined incidence of death, target lesion nonfatal myocardial infarction, repeat angioplasty, and coronary artery bypass graft surgery. Results A total of 308 patients （91.9%） completed the study and 145 cases （47.1%） received angiographic follow-up. The restenosis rates were significantly reduced in the XS0601 group as compared with the placebo group （26.0% vs. 47.2%, P 〈 0.05）, and the minimum lumen diameter （MLD） was greater [（2.08 ± 0.89） mm for XS0601 vs. （1.73 ± 0.94） mm for placebo, P 〈 0.05]. XS0601 also significantly reduced the combined incidence of major adverse cardiac event （10.4% in the XS0601 group vs. 22.7% in the placebo group, P 〈 0.05）. The incidence of recurrent angina at 3 and 6 months after PCI was also significantly reduced in XS0601 group （7.1% and 11.0%） as compared with those in placebo group （19.5% and 42.9%） （P 〈 0.05）. No significant side effects occurred within the 6-month follow-up period in the XS0601 group.Conclusion Administration of XS0601 for 6 months is demonstrated to be safe and effective in reducing restenosis in post-PCI patients.

A disintegrin and metalloproteinase with thrombospondin motif 1(ADAMTS1) expression increases in acute aortic dissection

Acute aortic dissection(AAD) is a life-threatening cardiovascular disease caused by progressive medial degeneration of the aortic wall. A disintegrin and metalloproteinase with thrombospondin motifs 1(ADAMTS1) is a recently identified extracellular metalloproteinase participating in the development of vascular disease, such as atherosclerosis. In the present study, we found that ADAMTS1 was significantly elevated in blood samples from AAD patients compared with patients with acute myocardial infarction and healthy volunteers. Based on these findings, we established an AAD model by infusing angiotensin II in older mice. AAD was successfully developed in aorta tissues, with an incidence of 42% after 14 days in the angiotensin II group. Macrophage and neutrophil infiltration was observed in the media of the aorta, and ADAMTS1 overexpression was found in the aorta by Western blot and immunohistochemistry. Double immunofluorescence staining showed the expression of ADAMTS1 in macrophages and neutrophils. Consistent with the upregulation of ADAMTS1 in aortic dissection tissues, versican(a proteoglycan substrate of ADAMTS1) was degraded significantly more in these tissues than in control aortic tissues. These data suggest that the increased expression of ADAMTS1 protein in macrophages and neutrophils that infiltrated aortic tissues may promote the progression of AAD by degrading versican.

Blood Pressure Targets in the Hypertensive Elderly

Objective： Hypertension is an important risk factor of cardiovascular disease and increases mortality in the elderly. However, the available medical evidences are both inconsistent and insufficient regarding establishing credible and useful blood pressure （BP） targets in the hypertensive elderly. This review summarizes the existing evidences used for establishing optimal BP targets for this patient population and points out some data inconsistencies which have added to the uncertainty. Data Sources： We conducted a search for the articles published in English in the PubMed database up to March 2017, with the keywords ＂hypertension,＂ ＂elderly,＂ ＂blood pressure,＂ and ＂antihypertensive.＂ Study Selection： Articles that related to BP targeting in the hypertensive elderly were selected for this review. Results： The selected studies indicated that antihypertensive therapy can substantially reduce the risk of cardiovascular events and mortality, for a subset of the elderly （60 years or older） with systolic BP 〉 160 mmHg. Studies regarding more strict targets yielded mixed findings. For the very old and frail patients （80 years or older）, there is a lack of evidence that optimal BP targets and intensive antihypertensives are helpful but in fact may be harmful. Conclusions： There are solid evidences that patients who are 60-80 years old and in good health have benefited from lowering their BP to below 150/90 mmHg. If well tolerated, the BP target can be further lowered to below 140/90 mmHg. However, for the very old and frail, individualized and careful assessment is crucial. Antihypertensive treatment should be cautious and the adverse effect of drugs requires close monitoring as such treatment can be counterproductive.

Garlicin Post-conditioning Suppresses Adhesion Molecules in Porcine Model of Myocardial Ischemia-Reperfusion Injury

Objective: To evaluate whether garlicin post-conditioning can attenuate myocardial ischemiareperfusion injury in a catheter-based porcine model of acute myocardial infarction(AMI) by affecting adhesion molecules integrin β1/CD29 and platelet endothelial cell adhesion molecule-1(PECAM-1/CD31). Methods: Twenty-two swine were devided into 3 groups: 6 in a sham-operation group, and 8 each in the model and garlicin groups. AMI porcine model was established in the model and garlicin groups. The distal parts of the left anterior descending coronary artery in the animals of the model and garlicin groups were occluded by dilated balloon for 2 h, followed by reperfusion for 3 h. Garlicin(1.88 mg/kg) was injected over a period of 1 h, beginning just before reperfusion, in the garlicin group. Real-time polymerase chain reaction, immunohistochemistry and Western blot were carried out to detect mRNA and protein expressions of CD29 and CD31 3 h after reperfusion. Results: Hematoxylin-eosin staining showed a better myocardial structure in the garlicin group after reperfusion. Compared to the model group, garlicin inhibited both the mRNA and protein expression of CD29 and CD31 in reperfusion area and no-reflow area(both P<0.05). Conclusions: Garlicin post-conditioning induced cardio-protection against myocardial ischemia-reperfusion injury in this catheter-based porcine model of AMI. The cardio-protective effect of garlicin is possibly owing to suppression of production of CD29 and CD31, by inhibition of the m RNA expression of CD29 and CD31.

ADAMTS-7 promotes vascular smooth muscle cells proliferation in vitro and in vivo

Vascular smooth muscle cell(VSMC) proliferation and migration are pivotal for the pathogenesis of atherosclerosis and post-angioplasty restenosis. We have recently reported that a disintegrin and metalloproteinase with thrombospondin motifs-7(ADAMTS-7), a novel metalloproteinase, contributes directly to neointima formation by mediating VSMC migration. However, whether ADAMTS-7 affects VSMC proliferation remains unclear. In this study, we found that luminal adenoviral delivery of ADAMTS-7 aggravated intimal hyperplasia 7 d after injury, paralleled by an increased percentage of PCNA-positive cells in both intima and media. In contrast, perivascular administration of ADAMTS-7 si RNA, but not scrambled si RNA to injured arteries attenuated intimal thickening at day 7, paralleled with reduced intimal VSMC replication, without alteration of VSMC proliferation in the media. In accordance, [3H]-thymidine incorporation assay in primary cultured rat VSMCs revealed an enhanced replication rate(by 61%) upon ADAMTS-7 overexpression and retarded proliferation(by 23%) upon ADAMTS-7 si RNA administration. Our data demonstrates that ADAMTS-7 promotes VSMC proliferation both in vitro and in vivo. ADAMTS-7 may therefore serve as a novel therapeutic target for atherosclerosis and post-angioplasty restenosis.

Effect of Dialysis on Antiplatelet Drug Efficacy in Uremic Patients with Coronary Heart Disease

Background： Coronary intervention therapy is the main treatment for uremic patients with coronary heart disease. The studies on whether dialysis reduces the efficacy of dual antiplatelet drugs are limited. The aim of this study was to examine the effect of dialysis on antiplatelet drugs in uremic patients with coronary heart disease. Methods： This study included 26 uremic patients who had undergone percutaneous coronary intervention in China-Japan Friendship Hospital from November 2015 to May 2017. We examined their thromboelastography results before and after hemodialysis. Self-paired t-tests were employed to analyze changes in the inhibition rate of platelet aggregation. Results： The mean inhibition rates of arachidonic acid-induced platelet aggregation before and after hemodialysis were 82.56 ± 2.79% and 86.42±3.32%, respectively （t =-1.278, P = 0.213）. The mean inhibition rates of adenosine diphosphate-induced platelet aggregation before and after hemodialysis were 67.87± 5.10% and 61.9± 5.90%, respectively （t = 1.425, P = 0.167）. There was no significant difference in the inhibition rates ofplatelet aggregation before or after hemodialysis. These results also applied to patients with different sensitivity to aspirin and clopidogrel. Conclusion： Dialysis did not affect the antiplatelet effects of aspirin and clopidogrel in uremic patients with coronary heart disease.

Optimized Axillary Vein Technique versus Subclavian Vein Technique in Cardiovascular Implantable Electronic Device Implantation： A Randomized Controlled Study

Background：The conventional venous access for cardiovascular implantable electronic device （CIED） is the subclavian vein,which is often accompanied by high complication rate.The aim of this study was to assess the efficacy and safety of optimized axillary vein technique.Methods：A total of 247 patients undergoing CIED implantation were included and assigned to the axillary vein group or the subclavian vein group randomly.Success rate of puncture and complications in the perioperative period and follow-ups were recorded.Results：The overall success rate （95.7% vs.96.0%） and one-time success rate （68.4% vs.66.1%） of punctures were similar between the two groups.In the subclavian vein group,pneumothorax occurred in three patients.The subclavian gaps of three patients were too tight to allow operation of the electrode lead.In contrast,there were no puncture-associated complications in the axillary vein group.In the patient follow-ups,two patients in the subclavian vein group had subclavian crush syndrome and both of them received lead replacement.The incidence of complications during the perioperative period and follow-ups of the axillary vein group and the subclavian vein group was 1.6% （2/125） and 8.2% （10/122）,respectively （χ^2=5.813,P =0.016）.Conclusion：Optimized axillary vein technique may be superior to the conventional subclavian vein technique for CIED lead placement.

Extracorporeal Cardiopulmonary Resuscitation in Children of Asia Pacific： A Retrospective Analysis of Extracorporeal Life Support Organization Registry

Background： Recent advances in extracorporeal membrane oxygenation （ECMO） have led to increasing interest in its use during cardiopuhnonary resuscitation （CPR）. However, decisions regarding extracorporeal CPR （ECPR） in children are difficult as a result of limited studies, especially in Asia Pacific. The objective of this study was to investigate trends in survival and demographic details for children with ECPR in Asia Pacific recorded in the Extracorporeal Life Support Organization （ELSO） registry from 1999 to 2016 and identify the risk factors associated with in-hospital mortality. Methods： The data of children younger than 18 years of age who received ECPR over the past 18 years in Asia Pacific were retrospectively analyzed. The data were extracted from the ELSO registry and divided into two 9-year groups （Group 1 1999-2007 and Group 2： 2008-2016） to assess temporal changes using univariate analysis. Then, univariate and multiple logistic regression analyses were performed between survivors and nonsurvivors to identify factors independently associated with in-hospital mortality. Results： A total of 321 children were included in final analysis, with an overall survival rate of 50.8%. Although survival rates were similar between Group 1 and Group 2 （43.1% vs. 52.5%,χ^2= 1.67, P - 0.196）, the median age （1.7 [0.3, 19.2] months for Group 1 vs. 5.6 [0.8, 64.9] months for Group 2, t = 2.93, P = 0.003） and weight （3.7 [3.0, 11.5] kg for Group 1 vs. 6.0 [3.4, 20.3] kg for Group 2, t = -3.14, P 0.002） of children increased over time, while the proportion of congenital heart disease （75.9% for Group 1 vs. 57.8% for Group 2, χ^2=6.52, P 0.011 ） and cardiogenic shock （36.2% for Group 1 vs. 7.2% for Group 2, χ^2=36.59, P 〈 0.001 ） decreased. Patient conditions before ECMO were worse, while ECMO complications decreased across time periods, especially renal complications. Multiple logistic regress!on analysis of ECMO complications showed that disseminated intravascular coagulation （DIC）, myocardial stunning, and neurological complications were independently associated with increased odds of hospital mortality. Conclusions： The broader indications and decreased complication rates make EPCR to be applicated more and more extensive in children in Asia Pacific region. ECMO complications such as myocardial stunning are independently associated with decreased survival.

ADAMTS-1 expression in rat myocardium after ischemic preconditioning： age-associated differences

Background It has been found that cardiac protection afforded by ischemic preconditioning （IPC） is significantly reduced in the senescent myocardium. ADAMTS-1 （a disintesrin and metalloprotease with thrombospondin type 1 motifs） has been shown to inhibit angiogenesis in a variety of in vitro and in vivo assays. The aim of this study was to investigate the age-associated differences in ADAMTS-1 protein expression in rat myocardium after ischemic preconditioning. Methods Sixty-four young （4 months） and old （24 months） male Sprague-Dawley rats were randomly assigned to an IPC group （40 rats） or a sham group （rats）. A model of delayed IPC was induced and rats were sacrificed and myocardial samples were harvested from the ischemic-reperfused region for immunohistochemical detection of ADAMTS-1 at serial time points after IPC. A model of myocardial infarction was produced by ligation of the left anterior descending coronary artery in additional sets of young and old rats after sham or IPC procedures, then age-associated myocardial infarction survival after IPC was calculated. Results ADAMTS-1 expression increased significantly in old rats compared to young rats （P 〈0.05）. The mean densities of ADAMTS-1 protein at 0, 6, 12, and 24 hours in young-IPC group after IPC were 0.05＋0.01, 0.13±0.03, 0.16±0.04, and 0.12±0.03 vs. 0.07±0.03, 0.20±0.03, 0.24±0.05, and 0.21±0.04 in old-IPC group. IPC resulted in diminished survival rates （5/35 vs. 6/14, old-IPC group vs shortening （（13.9±2.8）% vs. （18.3±2.3）%, P 〈0.05） and old-sham group, P 〈0.05）, reduced left ventricular fractiona increased the myocardial infarction size （（37.9±3.2）% vs （32.8±5.1）%, P 〈0.05） in the older rats. Conclusions Cardioprotection with IPC is attenuated in the older heart. ADAMTS-1 expression induced by IPC is greater in old rats. Over-expression of anti-angiogenic factors might be a potential mechanism behind reduced protection after IPC associated with aging.

Effect of Kuanxiong Aerosol(宽胸气雾剂)on Patients with Angina Pectoris:A Non-inferiority Multi-center Randomized Controlled Trial

Objective： To evaluate the effect and safety of Kuanxiong Aerosol （宽胸气雾剂, KA） on patients with angina pectoris. Methods： Block randomization was performed to randomly allocate 750 patients into KA （376 cases） and control groups （374 cases）. During an angina attack, the KA group received 3 consecutive sublingual sprays of KA （0.6 mL per spray）. The control group received 1 sublingual nitroglycerin tablet （NT, 0.5 rag/tablet）. Log-rank tests and Kaplan-Meier estimations were used to estimate the angina remission rates at 6 time-points after treatment （1,2, 3, 4, 5, and 〉5 min）. Logistic regression analysis was performed to observe the factors influencing the rate of effective angina remission, and the remission rates and incidences of adverse reactions were compared for different Canadian Cardiovascular Society （CCS） classes of angina. Results： The 5-min remission rates in the KA and control groups were not significantly different （94.41% vs. 90.64%, P〉0.05）. The angina CCS class significantly influenced the rate of remission （95% confidence interval = 0.483-0.740, P〈0.01）. In the CCS subgroup analysis, the 3- and 5-min remission rates for KA and NT were similar in the CCS I and IV subgroups （P〉0.05）, while they were significantly better for KA in the CCS Ⅱ and Ⅲ subgroups （P〈0.05 or P〈0.01）. Furthermore, the inciden0ce of adverse reactions was significantly lower in the KA group than in the control group for the CCS Ⅱ and Ⅲ subgroups （9.29% vs. 26.22%, 10.13% vs. 20.88%, P〈0.05 or P〈0.01）. Conclusions： KA is not inferior to NT in the remission of angina. Furthermore, in CCS Ⅱ and Ⅲ patients, KA is superior to NT, with a lower incidence of adverse reactions. （Registration No. ChiCTR- IPR-15007204）

Pathological Observation of Blood Stasis Syndrome in Non-diabetic Peripheral Neuropathies:A Retrospective Analysis Based on Nerve Biopsy

Objective To investigate the pathological features of blood stasis syndrome(BSS)in non-diabetic peripheral neuropathy.Methods Clinical data of 31 patients with non-diabetic peripheral neuropathy who had undergone nerve biopsy during December 2004 and December 2010 in Xuanwu Hospital Capital Medical University were retrospectively analyzed.According to Chinese medicine(CM)syndrome differentiation and signs,26 patients were blood stasis type and 5 patients were non-blood stasis type.Clinical and pathological data were compared in detail.Results Clinically,although both groups shared similar symptoms of limb numbness,weakness and sensory disturbances,the prevalence of neuralgia was much grievous in BSS group(73.1%,26/31)compared with the non-BSS group(0%,0/5).As for signs,dermal nutrients disturbance(84.6%,22/26),dark or purple tongue(100.0%,26/26),and sublingual varices(80.7%,21/26)were more common in the BSS group than the non-BSS group(0%,60%,20%,respectively).The prevalence of qi deficiency cases(19/26)in the BSS group was significantly higher compared with the non-BSS group(1/5).The unique histological manifestations of BSS were axonal degeneration(16/26 vs 2/5 in non-BSS group),which was the hallmark of ischemia.Cases with BSS had prominent microangiopathy(61.5%,16/26),manifested as epineurium vasculitis(inflammatory cell infiltrated to the vessel wall,obliteration and recanalization,vascular proliferation,extravascular hemosiderin deposition),angiotelectasis,proliferation and hyaline degeneration of endoneurium capillary.In the BSS group,impaired blood-nerve barrier was indicated by sub-perineurial edema(46.2%,11/26)and endoneurial edema(15.4%,4/26).The Renaut body(15.4%,4/26)and amyloid deposition(3.8%,1/26)found in the BSS group were absent in the non-BSS group.Conclusions BBS was common in non-diabetic peripheral neuropathies.The nerves exhibited ischemic alteration of primary axon degeneration and secondary demyelination.The interstitial tissue revealed microcirculation impairment,blood-nerve barrier disturbance,amyloid deposition and proliferation changes.The high prevalence of qi deficiency also highlights the therapy of promotion of blood circulation and removal of blood stasis.