[Long-term outcomes of intravascular ultrasound-guided drug-eluting stents implantation in patients with acute coronary syndrome: ULTIMATE ACS subgroup].

Objective: To explore the long-term effects of intravascular ultrasound (IVUS) guidance on patients with acute coronary syndrome (ACS) undergoing drug-eluting stents (DES) implantation. Methods: Data used in this study derived from ULTIMATE trial, which was a prospective, multicenter, randomized study. A total of 1 448 all-comer patients were enrolled between 2014 August and 2017 May. Primary endpoint of this study was target vessel failure (TVF) at 3 years, including cardiac death, target-vessel-related myocardial infarction, and clinically-driven target vessel revascularization. Results: ACS was present in 1 136 (78.5%) patients, and 3-year clinical follow-up was available in 1 423 patients (98.3%). TVF in the ACS group was 9.6% (109/1 136), which was significantly higher than 4.5% (14/312) in the non-ACS group (log-rank P=0.005). There were 109 TVFs in the ACS patients, with 7.6% (43/569) TVFs in the IVUS group and 11.6% (66/567) TVFs in the angiography group (log-rank P=0.019). Moreover, patients with optimal IVUS guidance were associated with a lower risk of 3-year TVF compared to those with suboptimal IVUS results (5.4% (16/296) vs. 9.9% (27/273),log-rank P=0.041). Conclusions: This ULTIMATE-ACS subgroup analysis showed that ACS patients undergoing DES implantation were associated with a higher risk of 3-year TVF. More importantly, the risk of TVF could be significantly decreased through IVUS guidance in patients with ACS, especially in those who had an IVUS-defined optimal procedure.

[Long-term outcomes of intravascular ultrasound-guided drug-eluting stent implantation in patients with chronic kidney disease: ULTIMATE CKD subgroup analysis].

Objective: To explore the long-term effect of intravascular ultrasound (IVUS) guidance on patients with chronic kidney disease (CKD) undergoing drug-eluting stent (DES) implantation. Methods: Data used in this study derived from ULTIMATE trial, which was a prospective, multicenter, randomized study. From August 2014 to May 2017, 1 448 patients with coronary heart disease undergoing DES implantation were selected from 8 domestic centers and randomly divided into two groups in the ratio of 1∶1 (IVUS or coronary angiography guided stent implantation). A total of 1 443 patients with the baseline serum creatine available were enrolled. The patients were divided into CKD group and non CKD group. CKD was defined as the estimated glomerular filtration rate (eGFR) derived from Cockcroft Gault (CG) formula< 60 ml·min-1·1.73 m-2 for at least 3 months. Primary endpoint of this study was target vessel failure (TVF) at 3 years, including cardiac death, target vessel myocardial infarction, and clinically-driven target vessel revascularization. Kaplan Meier method was used for survival analysis, and log rank test was used to compare the occurrence of end-point events in each group. Cox proportional hazards model was used to calculate HR and 95%CI, and interaction was tested. Multivariate Cox regression was used to analyze the independent influencing factors of TVF. Results: A total of 1 443 patients with coronary heart disease were enrolled in this study, including 349 (24.2%) patients in CKD group and 1 094 patients in non CKD group. In CKD group, IVUS was used to guide stent implantation in 180 cases and angiography was used in 169 cases; in non CKD group, IVUS was used to guide stent implantation in 543 cases and angiography was used in 551 cases. Three-year clinical follow-up was available in 1 418 patients (98.3%). The incidence of TVF in CKD group was 12.0% (42/349), which was higher than that in non CKD group (7.4% (81/1 094) (P = 0.01). The difference was mainly due to the higher cardiac mortality in CKD group (4.6% (16/349) vs. 1.5% (16/1094), P<0.001). In CKD group, the incidence of TVF in patients who underwent IVUS guided stent implantation was lower than that in angiography guided stent implantation (8.3% (15/180) vs. 16.0% (27/169), P = 0.03). There was no significant difference in the incidence of TVF between IVUS guided stent implantation and angiography guided stent implantation in non CKD group (5.9% (32/543) vs. 8.9% (49/551), P = 0.06), and there was no interaction (P = 0.47). Multivariate Cox regression analysis showed that IVUS guidance (HR = 0.56, 95%CI 0.39-0.81, P = 0.002), CKD (HR = 1.83, 95%CI 1.17-2.87, P = 0.010) and stent length (every 10 mm increase) (HR = 1.11, 95%CI 1.04-1.19, P = 0.002) were independent risk factors for TVF within 3 years after DES implantation. Conclusions: CKD patients undergoing DES implantation are associated with a higher risk of 3-year TVF. More importantly, the risk of TVF could be significantly decreased through IVUS guidance in comparison with angiography guidance in patients with CKD.

[Relationship between c-kit mRNA expression and prognosis in patients with rectal carcinoma].

Objective: To investigate the correlation between c-kit mRNA expression and prognosis in patients with rectal carcinoma. Methods: The expression of c-kit mRNA in rectal carcinoma tissues(n=66) was detected by multiplex branched-DNA liquid chip method. According to the expression level, the patients were classified into the c-kit mRNA high expression group and the low group. We analyzed the relationship between the c-kit mRNA expression and the clinicopathological characteristics of patients, as well as the factors affecting patients'prognosis. Results: Of the 66 rectal carcinoma patients, 18(27.3%)cases were c-kit mRNA high expression. No significant correlation was found between the c-kit mRNA expression and gender, age, preoperative carcinoembryonic antigen, preoperative hemoglobin, distance to verge, lymph node metastasis, tumor thrombus, T stage, TNM stage and tumor differentiation (P>0.05). In follow-up, 34 patients died, 32 patients and 36 patients were recurrence or metastasis. The 1-, 3-, 5-year overall survival(OS) of c-kit mRNA high expression group were 100.0%, 77.8%, 77.8%, respectively, while those of the low one were 93.8%, 56.3%, 45.8%, respectively. The difference was statistically significant(P=0.025). Lymph node metastasis, T stage and TNM stage were also significant associated with OS(P<0.05). The 1-, 3-, 5-year disease free rate (DFS)of the c-kit mRNA high expression group were 100.0%, 77.8% and 77.8%, respectively, while those of the low one were 77.1%、43.8% and 41.7%, respectively, and the difference between the two groups was significant (P=0.044). As a reslut, c-kit mRNA expression (P=0.038) and TNM stage (P=0.039) were the independent prognostic factors affecting the OS in rectal cancer patients. Conclusions: Low expression of c-kit was associated with poor prognosis of rectal carcinoma. And the mechanism underlying this phenomenon deserves further exploration.

Self-assembly of highly conductive self-n-doped fullerene ammonium halides and their application in the in situ solution-processable fabrication of working electrodes for alcohol electrooxidation.

Stable and highly conductive self-n-doped fullerene ammonium halides are promising optoelectronic materials. It is necessary to thoroughly understand their structure-function relationship and to develop their applications. Here, the assembly behaviors of the self-n-doped fullerene ammonium halides, as well as the functional areas in the well-developed 2D-3D lamellar structures in their ordered aggregates are systematically characterized using comprehensive methods. In the self-assembly, the solvation effect of DMSO promotes the flexibility of side-chains and drives the formation of fullerene ammonium halides into ordered bilayer structures. The conductivity-active area, which contains tightly packed halide anions sandwiched between fullerenes, provides good electron transfer property. Remarkably, residual DMSO in the side-chain area can induce aqueous Pd precursor into the highly conductive framework. After reduction, Pd nanoparticles are immobilized in the confined spaces within the conductive support. The resulting electrode can be used to electrooxidize ethanol. This study provides a facile solution strategy for the in situ fabrication of electrocatalysts on working electrodes, which can be applied in direct alcohol fuel cells.

[Effect of transcatheter aortic valve replacement using Venus-A valve for treating patients with severe aortic stenosis].

Objective: To evaluate the effect of transcatheter aortic valve replacement(TAVR) using Venus-A valve for treating patients with severe aortic stenosis. Methods: In this prospective study, 101 consecutive severe aortic stenosis patients with high surgical risk(Society of Thoracic Surgeon(STS) score ≥4%) or at prohibitive surgical risk were enrolled from 5 academic cardiovascular centers in China(Fuwai hospital, the second affiliated hospital of Zhejiang university school of medicine, West China hospital of Sichuan university, the first affiliated hospital of Nanjing medical university, Ruijin hospital of Shanghai Jiaotong university school of medicine) from September 2012 to January 2015, and Venus-A valves were used in TAVR for these patients. The primary endpoints were death from any cause and major stroke in 1 year. The secondary endpoints included efficacy and safety of TAVR in 1 year. Results: TAVR success rate was 97.9%(98/101), and 3 patients were transferred to receive surgical AVR. There were 85 patients using 1 Venus-A valve, and 13 patients underwent valve-in-valve implantation using 2 Venus-A valves. There were 1 case(1.0%) of stroke, 2 cases(2.0%)of acute myocardial infarction, 5 cases(5.0%) of pericardial effusion, 6 cases(5.9%) of severe vascular complication, and 2 cases(2.0%) of death after 7 days of TAVR. Meanwhile, aortic pressure gradient derived from echocardiography was significantly reduced when compared with pre-procedure level(11(8, 15) mmHg (1 mmHg=0.133 kPa) vs. 59(45, 71)mmHg, P<0.01), and there was no aortic root rupture or leaflets thrombosis. Rate of NYHA functional class ≤Ⅱ improvements were observed at 6 months follow-up when compared with pre-procedure(94.4%(84/89)vs. 21.3%(21/89), P<0.01). The primary endpoint was 7.9%(8/11), and the incidence of all cause death and stroke was 5.9%(6/101) and 2.0%(2/101) respectively at 1 year after the procedure. Kaplan-Meier survival analysis showed that cumulative survival rate was 94.1% at 1 year after the procedure. Conclusion: TAVR using Venus-A valve for treating patients with severe aortic stenosis is effective and safe in the early and medium term post procedure.

Association of miR-196a2, miR-27a, and miR-499 polymorphisms with isolated congenital heart disease in a Chinese population.

We hypothesized that single nucleotide polymorphisms (SNPs) in certain microRNAs contribute to congenital heart disease (CHD) phenotypes. Five hundred and seventy-three subjects were enrolled in this study. DNA extracted from peripheral blood cells was used for SNP genotyping of miR-196a2 (rs11614913), miR-27a (rs11671784, rs895819), and miR-499 (rs3746444). Allele and genotype association analyses were performed to evaluate the correlation between certain microRNA SNPs and three phenotypes of isolated CHD: atrial septal defect (ASD), ventricular septal defect (VSD), and patent ductus arteriosus (PDA). All the participants carried a homozygous CC variant of miR-27a (rs11671784). The homozygous CC variant of miR-196a2 (rs11614913, T>C) was negatively associated with ASD compared with the wild-type TT variant (OR = 0.379, 95%CI = 0.209-0.686, P = 0.001). The miR-196a2 C allele was negatively associated with ASD compared with the T allele (OR = 0.646, 95%CI = 0.491-0.849, P = 0.002). The statistically significant results were further confirmed by dominant and recessive model assays. SNPs of miR-27a (rs895819, T>C) and miR-499 (rs3746444, A>G) showed diverse association with ASD, VSD, or PDA, but the differences were not statistically significant. The rs11614913 (T>C) SNP of miR-196a2 is associated with ASD, and the homozygous CC variant and the C allele are protective factors associated with ASD. The homozygous CC variant and the C allele of the rs11614913 (T>C) SNP of miR-196a2 are associated with a significantly reduced risk of ASD.

Cytochrome c oxidase subunit VIIb as a potential target in familial hypercholesterolemia by bioinformatical analysis.

OBJECTIVE: The aim of the study is to explore the potential familial hypercholesterolemia markers by comparing with healthy controls. MATERIAL AND METHODS: We downloaded the gene expression profile GSE13985 from Gene Expression Omnibus database including five patients diagnosed with familial hypercholesterolemia (FH) and five age, sex, status matched controls. We applied t-test, Wilcox test and Fisher test in Multtest package of R language to identify the differentially expressed genes (DEGs) with p < 0.05 and |logFC| > 1, and constructed the interaction network of the top 3 up- and down-regulated genes using STRING. Besides, the modules of network were analyzed with Cytoscape and screened out with Mcode plugin, and the functional annotation of the genes involved in the modules was analyzed with BiNGO (Biological Networks Gene Ontology). RESULTS: Firstly, totally 101 differentially expressed genes were identified in FH samples compared with control samples, the genes ranked in top 3 up- and down-regulated genes were selected. Then, basing on the interaction network of these selected genes, ribosomal L24 domain containing 1 (RSL24D1) and cytochrome c oxidase subunit VIIb (COX7B) showed a central position in the interaction network, and also exited in the modules of the network. The functional annotation of the genes in modules showed that COX7B was associated with oxidative phosphorylation. CONCLUSIONS: COX7B might play vital roles in FH via oxidative phosphorylation system, and might be potential target in the treatment of FH.

Mutation p.S335X in GATA4 reduces its DNA binding affinity and enhances cell apoptosis associated with ventricular septal defect.

Genetic mutations in GATA4, a transcriptional factor, have been found to cause congenital heart diseases. The underlying mechanism, however, remains largely unknown. We previously reported 7 heterozygous variants in patients with ventricular septal defects (VSD). Here we functionally characterized a de novo mutation p.S335X and demonstrated that this mutation led to the pre-termination of its translation, producing a truncated GATA4 lacking a conservative region at C-terminus. Truncated GATA4 did not disturb its subcellular localization; however, it delayed the cardiomyocyte differentiation in P19cl6 model and prohibited Bcl2 expression that led to apoptosis proved by fragmented genomic DNA and positive TUNEL staining in H9C2 cells. By ChIP assay, we showed that GATA4 without C-terminus reduced its DNA binding affinity and suppressed the expressions of its target genes. These findings suggest that C-terminus of GATA4 is critical to maintain DNA binding, and genetic mutations in this region may affect genes important for myocyte apoptosis and differentiation associated with congenital heart defects.

A morphological study of the left atrial appendage in chinese patients with atrial fibrillation.

OBJECTIVE: Using angiography, this study examined left atrial appendage (LAA) morphology in Chinese patients with atrial fibrillation (AF) or congenital atrial septal defects (ASD), to provide data that might aid the design of new LAA-occluding devices to prevent cardioembolism and stroke in patients with AF. METHODS: Patients with AF or ASD were enrolled. The LAA was visualized angiographically; its dimensions were measured and the emptying fraction was calculated. RESULTS: A total of 45 patients with AF and 30 patients with ASD were included in the study. LAA morphology was classified into eight categories. The majority of patients with AF had tube-shaped LAAs with a single lobe; the most common LAA morphologies in patients with ASD were irregular or sphere-like, with multiple lobes. Patients with AF had significantly larger LAAs with significantly lower emptying fractions compared with LAAs of patients with ASD. CONCLUSIONS: The LAA demonstrated considerable morpho logical variability in terms of its size, shape and number of lobes. The design of new occluding devices must take into account the size and shape of the LAA in patients with AF.

Numerical simulation of microneedles' insertion into skin.

Microneedles have recently received much attention as a novel way for transdermal drug delivery. In this paper, a numerical simulation of the insertion process of the microneedle into human skin is reported using the finite element method. A multilayer skin model consisting of the stratum corneum, dermis and underlying hypodermis has been developed. The effective stress failure criterion has been coupled with the element deletion technique to predict the complete insertion process. The numerical results show a good agreement with the reported experimental data for the deformation and failure of the skin and the insertion force. The influences of the mechanical properties of the skin and the microneedle geometry (e.g. tip area, wall angle and wall thickness) on the insertion force are discussed. The numerical results are helpful for the optimum design of the microneedles for the transdermal drug delivery system.

Fabp3 inhibits proliferation and promotes apoptosis of embryonic myocardial cells.

Fatty acid binding protein 3 (FABP3) is a member of a family of binding proteins. The protein is mainly expressed in cardiac and skeletal muscle cells, and it has been linked to fatty acid metabolism, trafficking, and signaling. Using suppression subtractive hybridization, we previously found that FABP3 is highly regulated in ventricular septal defect (VSD) patients and may play a significant role in the development of human VSD. We therefore aimed to identify the biological characteristics of the FABP3 gene in embryonic myocardial cells. On the basis of RT-PCR and western blotting analyses, we demonstrated that the expression levels of FABP3 mRNA and protein were up-regulated initially and then gradually decreased with P19 cell differentiation. MTT assays and cell cycle analysis showed that FABP3 inhibits P19 cell proliferation, and data from annexin V-FITC assays revealed that FABP3 can promote apoptosis of P19 cells. Further data from quantitative real-time RT-PCR revealed lower expression levels of cardiac muscle-specific molecular markers (cTnT, alpha-MHC, GATA4, and MEF2c) in FABP3-overexpressing cell lines than in the control cells during differentiation. Our results demonstrate that FABP3 may be involved in the differentiation of cardiac myocytes.

Mosquito proboscis: an elegant biomicroelectromechanical system.

The mouthparts of female mosquitoes have evolved to form a special proboscis, a natural biomicroelectromechanical system (BMEMS), which is used for painlessly penetrating human skin and sucking blood. Scanning electron microscope observations show that the mosquito proboscis consists of a small bundle of long, tapering, and feeding stylets that are collectively called the fascicle, and a large scaly outer lower lip called the labium. During blood feeding, only the fascicle penetrates into the skin while the labium buckles back to remain on the surface of the skin. Here, we measured the dynamic force of penetration of the fascicle into human skin to reveal the mechanical principle underlying the painless process of penetration. High-speed video observations of movements associated with insertion of the fascicle indicate that the "smart" mosquito does not directly pierce its victim's skin with the fascicle. Instead, it uses the two maxillas as variable frequency microsaws with nanosharp teeth to advance into the skin tissue. This elegant BMEMS enables the mosquito to insert its feeding fascicle into human skin using an exceedingly small force (average of 16.5 µN).

Genome-wide association study of recurrent major depressive disorder in two European case-control cohorts.

Major depressive disorder (MDD) is a highly prevalent disorder with substantial heritability. Heritability has been shown to be substantial and higher in the variant of MDD characterized by recurrent episodes of depression. Genetic studies have thus far failed to identify clear and consistent evidence of genetic risk factors for MDD. We conducted a genome-wide association study (GWAS) in two independent datasets. The first GWAS was performed on 1022 recurrent MDD patients and 1000 controls genotyped on the Illumina 550 platform. The second was conducted on 492 recurrent MDD patients and 1052 controls selected from a population-based collection, genotyped on the Affymetrix 5.0 platform. Neither GWAS identified any SNP that achieved GWAS significance. We obtained imputed genotypes at the Illumina loci for the individuals genotyped on the Affymetrix platform, and performed a meta-analysis of the two GWASs for this common set of approximately half a million SNPs. The meta-analysis did not yield genome-wide significant results either. The results from our study suggest that SNPs with substantial odds ratio are unlikely to exist for MDD, at least in our datasets and among the relatively common SNPs genotyped or tagged by the half-million-loci arrays. Meta-analysis of larger datasets is warranted to identify SNPs with smaller effects or with rarer allele frequencies that contribute to the risk of MDD.

Cardiac lymphatic obstruction impairs left ventricular function and increases plasma endothelin-1 and angiotensin II in rabbits.

The treatment of end-stage heart failure can include heart transplantation. During this procedure, cardiac lymphatics are disrupted, which has been demonstrated in animal models to alter left ventricular function, and this compromise itself can cause an increase in endothelin-1 and angiotensin II. We undertook a study in rabbits to assess the effect of cardiac lymphatic obstruction on left ventricular function and plasma levels of endothelin-1 and angiotensin II. Sixty-three New Zealand white rabbits were divided into study (n = 41) and control (n = 22) groups. Plasma levels of endothelin and angiotensin II were measured before, and at 3, 7, 14, 30, 90 and 180 days following the obstruction of cardiac lymphatic vessels. Left ventricular function was assessed by echocardiography. Six months following the surgery, 18 study and 6 control animals survived. In the study group, a significant decrease was seen in left ventricular ejection fraction within the first three months following the lymphatic obstruction (0.76 +/- 0.04 vs 0.72 +/- 0.01, p < 0.01). Levels of plasma endothelin-1 and angiotensin II were elevated following ligation of cardiac lymphatic vessels with a peak between 3-7 days following lymphatic obstruction (all p < 0.05). Plasma endothelin-1 and angiotensin II began to decline 14 days after lymphatic obstruction and returned to almost baseline levels in 6 months. The left ventricular ejection fraction, plasma endothelin-1 and angiotensin in the control group remained unchanged (all p > 0.05). We conclude that cardiac lymphatic obstruction reduces left ventricular function in the first three months following obstruction. Cardiac lymphatic obstruction also increases plasma levels of endothelin-1 and angiotensin II. The clinical significance of these transitory changes requires further investigation.

Micronanostructures of the scales on a mosquito's legs and their role in weight support.

We show here that the mosquito cannot only give rise to a higher water-supporting force than the water strider if the ratio of the water-supporting force to the body weight of the insect itself is compared, but also can safely take off or land on the water surface, and also can attach on any solid surface like the fly. We found that the mosquito's legs are covered by numerous scales consisting of the uniform microscale longitudinal ridges (nanoscale thickness and microscale spacing between) and nanoscale cross ribs (nanoscale thickness and spacing between). Such special delicate microstructure and/or nanostructure on the leg surface give a water contact angle of approximately 153 degrees and give a surprising high water-supporting ability. It was found that the water-supporting force of a single leg of the mosquito is about 23 times the body weight of the mosquito, compared with a water strider's leg giving a water-supporting force of about 15 times the body weight of the insect.

Cardiac lymphatic interruption is a major cause for allograft failure after cardiac transplantation.

Cardiac transplantation is one of the most effective treatments of end stage heart failure to date, although it comes with risks. One of the major complications of cardiac transplantation is allograft failure, which is caused by ischemic injuries, pulmonary hypertension and chronic rejection. Recent animal and human studies have demonstrated that cardiac lymphatic obstruction leads to significant myocardial fibrosis and depression in contractile forces. We hypothesize that lymphatic interruption, which is almost inevitable after cardiac transplantation, is a major cause of cardiac allograft failure through direct damages to the myocardium and also through the formation of allograft coronary vasculopathy.

Prevalence of arrhythmias in patients with idiopathic dilated cardiomyopathy.

A total of 105 patients with idiopathic dilated cardiomyopathy (IDCM) underwent Holter monitoring. The prevalence of arrhythmias was as follows: ventricular premature beats (VPB) 100%, including complex VPB 58.1%, short runs of ventricular tachycardia (VT) 25.7%, A-VB or BBB 46.7%, atrial arrhythmias 38.1%, sinus node dysfunction 6.6%, ST-T change 38.1%. The incidence of ventricular arrhythmia (VA) was not related to severity of cardiac dysfunction (NYHA), duration of illness and sex. The most common arrhythmia was VA, the second one was heart block and atrial arrhythmia. Serum norepinephrine and epinephrine levels were 743.4 +/- 252.5 and 688.0 +/- 452.4 pg/ml, respectively, which were higher than those in control group (P < 0.01). Isoproterenol sensitivity test (ICD25) 8.43 +/- 11.21 micrograms, was also much higher than that in control group (P < 0.01). Average H-V interval was 69.4 +/- 13.3 msec in HBE. Eight patients died. Two died of congestive heart failure (class II-IV), and six cases were diagnosed as sudden cardiac death resulting from VT and VF.