Programmed cell death 4 as an endogenous suppressor of BDNF translation is involved in stress-induced depression.

Brain-derived neurotrophic factor (BDNF) is a growth factor that plays vital roles in the neuron survival, growth, and neuroplasticity. Alteration to BDNF expression is associated with major depressive disorder. However, the BDNF translational machinery in depression remains unknown. Herein, we pointed that Pdcd4, a suppressor oncogene, acted as an endogenous inhibitor for the translation of BDNF, and selectively repressed the translation of BDNF splice variant IIc mRNA in an eIF4A-dependent manner. Chronic restraint stress (CRS) up-regulated Pdcd4 expression in hippocampus via decreasing mTORC1-mediated proteasomes degradation pathway, which resulted in the reduction of BDNF protein expression. Moreover, over-expression of Pdcd4 in the hippocampus triggered spontaneous depression-like behaviors under the non-stressed conditions in mice, while systemic or neuron-specific knockout of Pdcd4 reverses CRS-induced depression-like behaviors. Importantly, administration of Pdcd4 siRNA or an interfering peptide that interrupts the Pdcd4-eIF4A complex substantially promoted BDNF expression and rescued the behavioral disorders which were caused by CRS. Overall, we have discovered a previously unrecognized role of Pdcd4 in controlling BDNF mRNA translation, and provided a new method that boosting BDNF expression through blocking the function of Pdcd4 in depression, indicating that Pdcd4 might be a new potential target for depressive disorder therapy.

New Discovery of Left Atrial Macroreentry Tachycardia: Originating from the Spontaneous Scarring of Left Atrial Anterior Wall.

AIMS: This study sought to describe left atrial macroreentry tachycardia (LAMRT) originating from the spontaneous scarring of left atrial anterior wall (LAAW) and its clinical and electrophysiological characteristics, mechanisms, and the formation of substrates. METHODS AND RESULTS: 9 of 123 patients (89% female, age 79.78 ± 5.59 years) had LAMRT originating from the LAAW with no cardiac surgery or prior left atrial (LA) ablation. The mean tachycardia cycle length (TCL) was 241.67 ± 38.00 milliseconds. Spontaneous scars areas and low voltage areas (LVAs) in the LAAW were found in all patients. Successful ablation of the critical isthmus caused termination of the LAMRT and was not inducible in all patients. Arrhythmogenic substrates of LAMRT were the spontaneous scars of LAAW, which matched with the aorta or/and pulmonary artery contact area. The area under the curve (AUC) of age and combination of gender and age for predicting the LAMRT originating from the LAAW were 0.918 and 0.951, respectively, with a cutoff value of ≥73.5 years of age and gender (female) predicting LAMRT with 88.9% sensitivity and 89% specificity. CONCLUSION: Combination of gender and age provides a simple and useful criterion to distinguish LAMRT from cavotricuspid isthmus- (CTI-) dependent atrial tachycardia in macroreentry atrial tachycardia (MRAT) in patients without a history of surgery or ablation. Aorta or/and pulmonary artery contacting LA may be related to spontaneous scars. Ablation the isthmus eliminated LAMRT in all patients.

[A case of tuberous sclerosis complex due to a novel splicing variant of TSC2 gene].

OBJECTIVE: To explore the genetic basis for a patient with tuberous sclerosis complex. METHODS: Genomic DNA was extracted from peripheral blood samples from members of his family and 100 unrelated healthy controls. The proband was subjected to next-generation sequencing, and candidate variant was confirmed by multiple ligation-dependent probe amplification (MLPA) and Sanger sequencing. Reverse transcription-PCR (RT-PCR) was carried out to determine the relative mRNA expression in the proband. RESULTS: The patient was found to harbor a c.2355+1G>C splicing variant of the TSC2 gene. Sequencing of cDNA confirmed that 62 bases have been inserted into the 3' end of exon 21, which has caused a frameshift producing a truncated protein. CONCLUSION: The novel splicing variant c.2355+1G>C of the TSC2 gene probably underlay the TSC in the proband. Above finding has expanded the variant spectrum of TSC2 and provided a basis for preimplantation genetic testing and/or prenatal diagnosis.

MiR-30a-5p inhibits osteosarcoma cell proliferation and migration by targeting FOXD1.

Despite a number of studies have emphasized the extensive role of microRNA (miRNA) in the development of multiple cancers, the role of miR-30a-5p in the progression of osteosarcoma (OS) and the underlying mechanism are still limited. We detected the expression level of MiR-30a-5p and forkhead box D1 (FOXD1) in Clinical OS specimens and found that miR-30a-5p was significantly decreased while FOXD1 was markedly increased. Dual luciferase assay confirmed that FOXD1 was directly regulated by miR-30a-5p. In vitro assay showed that inhibitior of FOXD1 suppressed cell proliferation, migration and invasion in MG63 and U2OS cells, while overexpression of FOXD1 promoted OS cell proliferation and migration. In vivo assay further showed the inhibition of tumor growth after knockdown of FOXD1. These results suggested that FOXD1 might play key roles in OS development and progression, and was negatively regulated by miR-30a-5p in OS.

Oral sophocarpine protects rat heart against pressure overload-induced cardiac fibrosis.

CONTEXT: Sophocarpine, a tetracyclic quinolizidine alkaloid, is one of the most abundant active ingredients in Sophora alopecuroides Linn. (Kudouzi). Sophocarpine injection was found to have significant antiviral effects against coxsackievirus B3 and therapeutic effects for viral myocarditis in the clinic. OBJECTIVE: This study assessed the effects of sophocapine on overload-induced cardiac fibrosis and investigated potential mechanisms. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were subjected to a suprarenal abdominal aorta constriction (AC) or sham to induce sustained pressure overload. Six weeks later, rats were randomly assigned to receive sophocapine (10, 20, and 40 mg/kg, gavage) or vehicle treatment for an additional 6 weeks. Six weeks after treatment, cardiac dysfunction, cardiac coefficient, cardiac fibrosis, hydroxyproline concentration, and inflammation mediators were examined. RESULTS: When compared with the model group, the left ventricular weight/body weight decreased by 25.4% and 39.0% in 20 and 40 mg/kg sophocarpine groups, respectively. The beneficial effects were associated with amelioration of left ventricular systolic pressure (LVSP) and left ventricular enddiastolic pressure (LVEDP). Moreover, pressure overload-induced cardiac fibrosis was attenuated in sophocarpine treated groups. Importantly, sophocarpine (20 and 40 mg/kg) decreased pro-inflammatory cytokine levels (IL-6, 14.6% and 18.5%; IL-1ß, 23.1% and 32.6%), collagen content (27.7% and 50.1%), as well as matrix metalloproteinases-2, 9 (MMP-2, 9) expression (MMP-2, 11.8% and 18.5%; MMP-9, 16.2% and 21.1%). Sophocarpine (40 mg/kg) inhibited IκB-α phosphorylation (19.0%). CONCLUSION: These findings indicated that sophocarpine potentially had antifibrotic effects. The mechanism might be due to modulation of the balance between pro-inflammatory cytokine expression and collagen content level as well as MMPs expression via the NF-κB signaling pathway.

An annotated grain kernel image database for visual quality inspection.

We present a machine vision-based database named GrainSet for the purpose of visual quality inspection of grain kernels. The database contains more than 350K single-kernel images with experts' annotations. The grain kernels used in the study consist of four types of cereal grains including wheat, maize, sorghum and rice, and were collected from over 20 regions in 5 countries. The surface information of each kernel is captured by our custom-built device equipped with high-resolution optic sensor units, and corresponding sampling information and annotations include collection location and time, morphology, physical size, weight, and Damage & Unsound grain categories provided by senior inspectors. In addition, we employed a commonly used deep learning model to provide classification results as a benchmark. We believe that our GrainSet will facilitate future research in fields such as assisting inspectors in grain quality inspections, providing guidance for grain storage and trade, and contributing to applications of smart agriculture.

Re-recognize early recurrence of persistent atrial fibrillation.

Aims: Few studies on early recurrence (ER) focused on patients with persistent atrial fibrillation (AF). We aimed to investigate the characteristics and clinical significance of ER in patients with persistent AF after catheter ablation (CA). Methods: A total of 348 consecutive patients who underwent first-time CA for persistent and long-standing persistent AF between January 2019 and May 2022 were investigated. Results: About 5/348 (1.44%) patients who failed to convert to sinus rhythm after CA were excluded. A total of 110/343 (32.1%) patients had ER, in which 98 (89.1%) were persistent and 50.9% occurred in the first 24 h after CA. Compared with the patients without ER, those with ER were more likely to have late recurrence (LR) (92.7% vs. 1.7%, P < 0.001) during a median follow-up of 13 (IQR 6-23) months. ER was the most significant independent predictor for LR (OR 120.5, 95% CI 41.5-349.8, P < 0.001). ER as atrial flutter (AFL) had a lower risk of LR when compared with ER as AF (P = 0.011) and both AF and AFL (P = 0.003). Early intervention of the patient with ER improved the short-term outcomes (P < 0.001), not long-term outcomes. Only 22/251 (8.76%) patients of LR appears among those who had no recurrence in the first month. Conclusions: Patients with persistent AF may not have a blanking period but rather have a risk period. Clinical significance of the blanking period should be given differential treatment between paroxysmal AF and persistent AF.

Short-coupled variant of torsade de pointes: A systematic review of case reports and case series.

Background: The short-coupled variant of torsade de pointes (scTdP) is characterized by a particular electrocardiogram (ECG) pattern that shows a short-coupling interval of the initial Tdp beat and that can degenerate into ventricular fibrillation without the presence of structural heart disease. However, its etiology, epidemiology, clinical characteristics, underlying mechanism, treatment, and prognosis remain unclear. This study aimed to systematically review case reports and series of scTdP to synthesize existing data on the demography, clinical characteristics, ECG features, management, and outcomes. Methods: A literature search was conducted for eligible published articles using the Medline, Embase, and PubMed databases. All eligible case reports and case series were included without any language restrictions. SPSS 24 was used for statistical analysis. Results: A total of 22 case reports and 103 case series of patients with scTdP were identified and included in the analysis. All selected cases had acceptable quality of evidence. Most young patients without sex differences had no trigger or a negative programmed simulation. The ECGs of all selected patients showed a short first-coupling interval (302 ± 62 ms) and a long QRS duration of ventricular extrasystole (VE) (135 ± 17 ms). The first coupling interval levels and QRS duration levels of VE were significantly longer and wider in patients with scTdP originating from the right ventricular outflow tract (RVOT) than in those with scTdP originating from the Purkinje fibers (380 ± 70 vs. 274 ± 28 ms, P < 0.001; 147 ± 8 vs. 131 ± 17 ms, P < 0.001), respectively. The receiver operating characteristic curve showed that the optimal cutoff values of the first coupling interval triggering TdP and QRS duration of VE were more than 319 ms and 141 ms (92% sensitivity, 95.7% specificity; 82.6% sensitivity, 77.8% specificity) for predicting the RVOT origin, respectively. The Kaplan-Meier survival curve revealed increased survival in patients with implantable cardioverter defibrillator (ICD) implantation than in patients without ICD implantation (log-rank =10.127, P = 0.001). Conclusion: Some agreements were confirmed in selected case reports regarding the clinical features, diagnosis, and management of scTdPs. Further large-scale and long-term follow-up studies are required to clarify the existing arrhythmogenic entities.

Effectiveness and Safety of High-Power Radiofrequency Ablation Guided by Ablation Index for the Treatment of Atrial Fibrillation.

Background: To investigate the efficacy and safety of ablation index- (AI-) guided high-power radiofrequency ablation in the treatment of atrial fibrillation (AF). Methods: Outcomes of radiofrequency (RF) applications were compared in a swine ventricular endocardial model (n = 10 each for 50 W, 40 W, and 30 W; AI = 500). And a total of 100 consecutive patients with paroxysmal AF undergoing pulmonary vein isolation (PVI) were included. The patients were divided into two groups (n = 50 for each) as follows: control group, treated with conventional power (30 W) ablation mode; and study group, treated with high power (40 W) radiofrequency ablation mode. All groups were treated with the same AI value guided the ablation (target AI = 400/500 on posterior/anterior wall, respectively). Acute pulmonary vein (PV) reconnection was assessed post adenosine administration 20 minutes after ablation. Subsequently, pathological observation of porcine heart lesions and necrotic tissue was performed. Additionally, statistical analyses were carried out on patients' baseline clinical characteristics, surgical data, and total RF energy. Results: In swine ventricular endocardial RF applications, compared with 40 W and 30 W, the use of 50 W was associated with shallower tissue lesion depth (p < 0.001) and greater lesion maximum diameter (p < 0.001). Compared with 40 W and 30 W, tissue necrosis caused by 50 W was the deepest and largest (p < 0.001). In pulmonary vein isolation (PVI), there was no significant difference in baseline data between the study group and control group (p > 0.05). In patients with paroxysmal atrial fibrillation, the procedure time in the high-power group was significantly shortened (p < 0.001). The ablation time was significantly shorter (p < 0.001). Compared with control group, RF energy per point and acute pulmonary vein (PV) reconnection were lower (p < 0.001), and first-pass PVI was higher (p < 0.01) in study group. There were no significant differences in complications and sinus rhythm maintenance at 12 months between the two groups (p > 0.05). Conclusions: Compared with conventional (30 W) PVI, AI-guided high-power (40 W) was safe and associated with shorter procedure time and reduced acute PV reconnection.

Catheter ablation in combined procedures is associated with residual leaks.

Objectives: To compare patients with atrial fibrillation (AF) undergoing left atrial appendage closure (LAAC) with catheter ablation (CA) and those without CA. Background: The CA of AF may cause ridge edema, which may affect the safety of LAAC. Methods: Patients with AF (N = 98) who underwent LAAC (combined CA + LAAC procedure group; N = 51) or alone (LAAC group; N = 47) received pre-procedural, intra-procedural, and 6 week post-procedural transesophageal echocardiography (TEE). The depth and ostial diameter of LAA, device compression, residual leak, and ridge thickness were evaluated in the patients who had undergone combined and alone procedures, as well as images of LAA and primary clinical characteristics. Results: A residual leak was identified in 27 patients at 6 weeks after implantation by TEE (19 in the combined procedures group and eight in the alone group; p = 0.04). The combined procedure group had a significantly higher rate of a new residual leak than the alone group (25.5 vs. 8.5%; p = 0.03). Meanwhile, compared with at the time of implant, a smaller amount of device compression ratio was significant after 6 weeks (22.44 ± 3.90 vs. 19.59 ± 5.39; p = 0.03). There was no significant difference between both groups in all-cause mortality, cardiovascular mortality, and TIA/stroke/system embolism. Conclusion: The combined procedures of CA and LAAC for AF are feasible and safe; however, during the follow-up period, we found that the resolution of ridge edema caused by CA might cause an increased residual leak and a smaller device compression ratio.

IL-37d Negatively Regulates NLRP3 Transcription via Receptor-mediated Pathway and Alleviates DSS-induced Colitis.

BACKGROUND: Interleukin-37 (IL-37) is a new negative immune regulator. It has 5 splicing forms, IL-37a-e, and most research mainly focuses on IL-37b functions in diverse diseases. Our previous research found that IL-37d inhibits lipopolysaccharide-induced inflammation in endotoxemia through a mechanism different from that of IL-37b. However, whether IL-37d plays a role in colitis and the underlying mechanisms is still obscure. Herein, we identified whether IL-37d regulates NLRP3 inflammasome activity and determined its effect on colitis. METHODS: NLRP3 inflammasome in macrophages from IL-37d transgenic (IL-37dtg) and control wild type (WT) mice were activated by lipopolysaccharide and adenosine 5'-triphosphate. The expression of NLRP3 inflammasome components and its downstream effector, IL-1ß, were detected by real-time polymerase chain reaction, western blot, and ELISA. The models of alum-induced peritonitis and dextran sodium sulfate (DSS)-induced colitis were used to investigate the function of IL-37d on regulating the activity of NLRP3 inflammasome in vivo. RESULTS: Our results showed that the activation of NLRP3 inflammasome in macrophage and alum-induced peritonitis was inhibited by IL-37d. Strikingly, IL-37d suppressed NLRP3 expression at the priming step via inhibiting NF-κB activation by transcriptional profiling. Moreover, the recombinant protein IL-37d attenuated NLRP3 inflammasome activation and the production of IL-1ß, which could be reversed by IL-1R8 knockdown. Finally, IL-37d transgenic mice resisted DSS-induced acute colitis and NLRP3 inflammasome activation. CONCLUSION: Interleukin-37d inhibits overactivation of the NLRP3 inflammasome through regulating NLRP3 transcription in an IL-1R8 receptor-mediated signaling pathway.

A novel ablation strategy of premature ventricular contractions originating from summit guided by CartoUNIVU module.

BACKGROUND: Premature ventricular contractions (PVCs) from left ventricular (LV) summit remain challenging for the risk of coronary artery injury. Computed tomographic or intracardiac echocardiography may be helpful, but both still have many limitations. CartoUNIVU module has rarely been used in PVC ablation. METHODS: A total of 22 patients (14 men: mean age 56.4 ± 13.3 years) with an electrocardiogram indication of summit PVCs were included in the two centers study. A novel strategy ablation with the Image Integration Module CartoUNIVUTM module was performed for all the patients with PVCs originating from LV summit area, especially to prevent the coronary artery injury. RESULTS: The procedure time was 78.6 ± 22.7 minutes, and the fluoroscopy time was 12.5 ± 3.1 minutes. The distance between the target and nearest coronary artery was 8.0 ± 3.1 mm. Three patients with the distance to the nearest coronary artery <5 mm. During a mean follow-up of 11.0 ± 1.7 months, 21/22 (95.5%) patients were free from clinical PVC. No coronary artery injury was detected in the all the ablation procedures. CONCLUSION: The novel strategy ablation with the Image Integration Module CartoUNIVU module is safe and effective for PVCs originating from LV summit area, especially to prevent the coronary artery injury.

Advances in the chemistry, pharmacological diversity, and metabolism of 20(R)-ginseng saponins.

Ginseng has been used as a popular herbal medicine in East Asia for at least two millennia. However, 20(R)-ginseng saponins, one class of important rare ginsenosides, are rare in natural products. 20(R)-ginseng saponins are generally prepared by chemical epimerization and microbial transformation from 20(S)-isomers. The C20 configuration of 20(R)-ginseng saponins are usually determined by 13C NMR and X-ray single-crystal diffraction. 20(R)-ginseng saponins have antitumor, antioxidative, antifatigue, neuroprotective, and osteoclastogenesis inhibitory effects, among others. Owing to the chemical structure and pharmacological and stereoselective properties, 20(R)-ginseng saponins have attracted a great deal of attention in recent years. In this study, the discovery, identification, chemical epimerization, microbial transformation, pharmacological activities, and metabolism of 20(R)-ginseng saponins are summarized.

Combination of catheter ablation for non-valvular atrial fibrillation and left atrial appendage occlusion in a single procedure.

Patients with atrial fibrillation (AF) have an increased risk of stroke and systemic embolism. Catheter ablation (CA) is increasingly applied for the treatment for drug-refractory AF; however, its long-term success rate is <50%. It has been proved that percutaneous left atrial appendage occlusion (LAAO) exerts the same efficacy as novel oral anti-coagulants [(N)OACs] in reducing thromboembolic events. The present study investigated whether a combined procedure of AF ablation and LAAO may be feasible and efficacious. CA was performed for patients with AF and a high risk of stroke according to their CHADS2 or CHA2DS2-VASc score, and LAAO was performed using the Watchman device. A total of 25 patients (40% females; mean age, 64.2±3.5 years) who were treated between July 2016 and June 2017 were included in the present study. The median CHA2DS2-VASc score was 4.5 (range, 2-6) and the median HAS-BLED score was 3.17 (range, 1-7). Successful CA and LAAO were performed in 100% of cases. All patients met the criteria for successful LAAO. At the 6-month follow-up, complete sealing of the LAA was achieved in 23 patients (92%), while a minimal residual flow (<5 mm) was detected in 2 patients (8%). In 24 patients (96%), the administration of (N)OACs was terminated and aspirin administration was initiated at the 6-month follow-up. (N)OAC treatment was maintained in 1 patient (4%) on the basis of transient ischemic attack. During the 6-month follow-up period, 3 patients who had a recurrence of AF received a repeated ablation. In conclusion, the combination of CA and LAAO in a single procedure is feasible, safe and efficacious for patients with non-valvular AF at a high risk of stroke, and a contraindication regarding the use of (N)OACs.

IL-37 isoform D downregulates pro-inflammatory cytokines expression in a Smad3-dependent manner.

IL-37 is a new member of IL-1 family and possesses five different isoforms (named as IL-37 a-e). IL-37b has been demonstrated as a physiological suppressor of immune responses. However, the function of other isoforms remains unknown. Here, we show that IL-37d possesses anti-inflammatory roles both in vitro and in vivo. Firstly, IL-37d is expressed in peripheral blood mononuclear cells (PBMCs) and umbilical cords-derived mesenchymal stem cells (UCMSCs). Secondly, IL-37d overexpression markedly inhibits IL-1ß-induced IL-6 production in A549 cells. Consistently, bone marrow-derived macrophages (BMDMs) from IL-37d transgenic mice express low levels of pro-inflammatory cytokines (such as IL-6 and TNF-α) following LPS stimulation, compared with those from wild-type mice. Furthermore, IL-37d transgenic mice produce less pro-inflammatory cytokines, and show much less degree of LPS-induced endotoxemia in vivo. Mechanistically, IL-37d interacts with Smad3 and promotes nuclear translocation of pSmad3. SIS3 (a specific Smad3 inhibitor) treatment completely blocks the inhibitory effects of IL-37d. Thus, our data indicate that IL-37d is a functional cytokine that negatively regulates pro-inflammatory cytokines expression in a Smad3-dependent manner.

Pre-synaptic TrkB in basolateral amygdala neurons mediates BDNF signaling transmission in memory extinction.

Brain-derived neurotrophic factor (BDNF) and its high affinity receptor, TrkB, play an essential role in memory extinction. Our previous work has shown that JIP3 (JNK interacted protein 3) mediates anterograde axonal transport of TrkB through the direct binding of its coiled-coil domain 1 (CC1) with TrkB. Here, we constructed a fluorescent CC1 and enhanced green fluorescent protein (EGFP) fused protein, CC1-EGFP, and found that CC1-EGFP could specifically interrupt TrkB anterograde axonal transport and its localization at the pre-synaptic site. Consistent with this, TrkB-mediated pre-synaptic vesicle release and retrograde axonal signaling transmission were disrupted by CC1-EGFP. Neuronal expression of CC1-EGFP in the basolateral amygdala (BLA) impaired fear memory extinction. And, it blocked BDNF in the BLA-induced enhancement of TrkB phosphorylation in the infralimbic prefrontal cortex (IL). Together, this study not only suggests that pre-synaptic TrkB in BLA neurons is necessary for memory extinction and contributes to the BDNF signaling transduction from the BLA to IL, but also provides CC1-EGFP as a novel tool to specifically regulate pre-synaptic TrkB expression in vitro and in vivo.

Association of white blood cell counts with left ventricular mass index in hypertensive patients undergoing anti-hypertensive drug therapy.

Although studies using animal models have demonstrated that nonhemodynamic factors, including inflammatory cells and cytokines, contribute to left ventricular hypertrophy (LVH), there is little clinical data to confirm this association. Therefore in the present study, levels of circulating specific types of leukocyte were measured to determine the association between white blood cells and left ventricular mass index (LVMI) in hypertensive patients undergoing anti-hypertensive drug therapy. A total of 144 consecutive hypertensive patients taking anti-hypertensive drug therapy were enrolled in the current study. Subjects were divided into two groups: Those with normal geometry and those with left LVH. Total white blood cells and differentiated subtypes (neutrophils, lymphocytes, monocytes) were counted, and left ventricular end-diastolic diameter, left ventricular posterior wall thickness in diastole and inter-ventricular septal wall thickness in diastole were all measured. Analysis revealed a significant correlation between LVMI and total white blood cell levels (P=0.013). The percentage of LVH in the highest tertile of WBC was increased compared with the middle tertile (P=0.008). Furthermore, a significant correlation between the highest tertile of neutrophil counts and LVH was observed (P=0.039). However, no significant associations between LVMI and monocyte or lymphocyte counts were detected. Therefore, the current study determined that increased total white blood cell and neutrophil subtype counts were associated with LVMI in hypertensive patients undergoing anti-hypertensive drug therapy. They may provide convenient and useful markers for further risk appraisal of LVH caused by nonhemodynamic factors of hypertension.

Second-generation versus first-generation drug-eluting stents in saphenous vein graftdisease: A meta-analysis of randomized controlled trials.

BACKGROUND: Second-generation drug-eluting stents (DESs) have become increasingly popular devices for patients with saphenous vein graft (SVG) disease. Second-generation DESs were designed to have more safety and efficacy than first-generation DES, but clinical outcomes in SVG disease remain conflicting. METHODS AND RESULTS: Randomized controlled trials (RCTs) were identified when comparing second- versus first-generation DESs in SVG disease. The main endpoint was all-cause death. The time of follow-up was at least 30days. The secondary endpoints were major adverse cardiovascular events (MACEs), target vessel revascularization (TVR), target lesion revascularization (TLR), myocardial infarction (MI), and stent thrombosis. These endpoints were assessed at 30days, 12months and 24months. Four RCTs with 1077 SVG patients undergoing the implantation of DES were collected in the current meta-analysis. As a result, second-generation DES-treated patients had the significantly lower MACE rates at 12months (P=0.03; OR: 0.69, 95% CI: 0.49,0.97). No differences in two groups were seen in all-cause death, MI, TVR, stent thrombosis and TLR. CONCLUSIONS: Our limited evidence indicated that, second-generation DES in SVG patients, compared with first-generation DES, offered similar levels of safety, but were more effective than the former one.

Tumor necrosis factor-alpha G-308 A polymorphism and risk of coronary heart disease and myocardial infarction: A case-control study and meta-analysis.

OBJECTIVES: The tumor necrosis factor-alpha (TNF-α) gene may play an important role in coronary heart disease (CHD) and myocardial infarction (MI) risk. Recently, controversial results regarding the association of the G-308 A (rs1800629)polymorphism of the TNF-α gene with CHD/MI have been reported. We herein examine a possible association between the G-308 A (rs1800629)polymorphism of the TNF-α gene and CHD/MI in a sample of the Chinese Han population. MATERIALS AND METHODS: We determined the genotypes of TNF-α G-308 A (rs1800629) in 535 unrelated Chinese patients with CHD, 420 patients with MI, and 1020 coronary artery disease-free controls. Additionally, a meta-analysis of all previous studies on the TNF-α G-308 A polymorphism and the risk of CHD and MI was performed. RESULTS: AA genotypes in the G-308 A (rs1800629)polymorphism of the TNF-α gene did not occur more frequently in CHD/MI patients than in controls; odds ratios (95% confidence intervals) were 1.743 (0.325 to 1.423) for CHD and 1.731 (0.442 to 1.526) for MI, after adjusting for conventional risk factors. Further stratification for age, gender, and other cardiovascular risk factors did not alter the prior negative findings. Pooled meta-analysis of 23 studies also found no statistically significant associations between the TNF-α polymorphism and CHD/MI risk in the genetic additive, dominant, and recessive models. Subgroup analyses showed no association between the TNF-α polymorphism and CHD/MI in Asian and Caucasian populations. CONCLUSION: Our study showed no association between the G-308 A (rs1800629) polymorphism of the TNF-α gene (presence of A allele) and CHD/MI in the Chinese Han population. There was no evidence of a difference in risk effects of rs1800629 between Caucasians and Asians.

Association between endothelial nitric oxide synthase polymorphisms and atrial fibrillation: a meta-analysis.

Several recent studies have focused on the association between the promoter polymorphisms 786T/C of the endothelial nitric oxide synthase (eNOS) gene and susceptibility to atrial fibrillation (AF); however, results have been conflicting. We searched Medline, Embase, and the ISI Web of Science through July 1, 2011. Five studies with 1,130 AF cases and 2,340 controls were selected. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated based on fixed- and random-effects models. There was no overall association between eNOS 786T/C and AF risk. In subgroup analysis, stratified by ethnicity, we observed a positive association between the eNOS 786T/C polymorphism and AF risk among Caucasians but not among mixed populations. When stratifying by control source, the overall ORs for population- and hospital-based studies were 1.07 (95% CI, 0.50-2.30) and 0.79 (95% CI, 0.65-0.97) for CC vs. 22T carriers, respectively. In the studies with a sample size greater than 200, the eNOS 786T/C polymorphism decreased AF risk (OR [95% CI]: 0.79 [0.64-0.97] for CC vs. T carriers). This meta-analysis suggests that the 786T/C polymorphism of the eNOS gene is protective against AF risk among Caucasians. Additional large studies based on diverse populations are required to validate this conclusion.