Left Ventricular Systolic Dysfunction and Cardiovascular Outcomes in Tetralogy of Fallot: Systematic Review and Meta-analysis

BackgroundAlthough there are robust data about the pathophysiology and prognostic implications of left ventricular (LV) systolic dysfunction in patients with acquired heart disease, similar prognostic data about LV systolic dysfunction are sparse in the tetralogy of Fallot (TOF) population. The purpose of this study was to perform a meta-analysis of all studies that assessed the relationship between LV ejection fraction (LVEF) and cardiovascular adverse events (CAEs) defined as death, aborted sudden death, or sustained ventricular tachycardia.MethodsWe used random-effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsOf the 1,809 citations, 7 studies with 2,854 patients (age 28 ± 4 years) were included. During 5.6 ± 3.4 years' follow-up, there were 82 deaths, 17 aborted sudden cardiac deaths, and 56 sustained ventricular tachycardia events. Overall, CAEs occurred in 5.1% (144 patients). As a continuous variable, LVEF was a predictor of CAE (HR 1.29, 95% CI, 1.09-1.53, P = 0.001) per 5% decrease in LVEF. Similarly, LVEF < 40% was also a predictor of CAE (HR 3.22, 95% CI, 2.16-4.80, P < 0.001).ConclusionsLV systolic dysfunction was an independent predictor of CAE, and we observed a 30% increase in the risk of CAE for every 5% decrease in LVEF, and a 3-fold increase in the risk of CAE in patients with LVEF <40% compared with other patients. These findings underscore the importance of incorporating LV systolic function in clinical risk stratification of patients with TOF and the need to explore new treatment options to address this problem.     

Comparison of Transcallosal Inhibition Between Hemispheres and Its Relationship with Motor Behavior in Patients with Severe Upper Extremity Impairment After Subacute Stroke

ObjectiveTo compare corticospinal excitability and transcallosal inhibition between contralesional primary motor cortex (M1) and ipsilesional M1. We also investigated the correlation between transcallosal inhibition and upper extremity motor behavior.Materials and methods19 individuals with unilateral ischemic subacute stroke who had severe upper extremity impairment participated in this study. Corticospinal excitability was assessed by measuring the resting motor threshold, active motor threshold and motor evoked potential amplitude. Transcallosal inhibition was investigated by measuring the duration and depth of the ipsilateral silent period (ISP). The data from the two hemispheres were compared and the relationships of transcallosal inhibition with upper extremity motor impairment, grip strength and pinch strength were analyzed.ResultsResting motor threshold (p = 0.001) and active motor threshold (p = 0.001) were lower and motor evoked potential amplitude was higher (p = 0.001) in the contralesional M1 compared to the ipsilesional M1. However, there were no differences between the two M1s in ISP duration (p = 0.297) or ISP depth (p =0. 229). Transcallosal inhibition from the contralesional M1 was positively associated with motor impairment (ISP duration, p = 0.003; ISP depth, p = 0.017) and grip strength (ISP duration, p = 0.016; ISP depth, p = 0.045).ConclusionsSymmetric transcallosal inhibition between hemispheres and positive association of transcallosal inhibition from contralesional M1 with upper extremity motor behavior indicate that recruitment of contralesional M1 may be necessary for recovery in patients with severe upper extremity impairment after subacute ischemic stroke.     

An amalgam of pathogenic and beneficial endophytic fungi colonizing four Dendrobium species from Meghalaya,India

Endophytic fungi are known to play an important role in driving the evolution of plants by conferring adaptational advantages to their host through the production of secondary metabolites and phytohormones. In this study, we evaluated the diversity and phylogenetic relationship of endophytic fungal communities from four Dendrobium species viz., Dendrobium chrysanthum, Dendrobium heterocarpum, Dendrobium hookerianum, and Dendrobium longicornu of Meghalaya, India. A total of 51 culturable endophytic fungi were isolated from the four selected orchid species. The isolates were identified based on nuclear large subunit sequences into 33 species. Approximately 91% of the isolates showed affinity to Ascomycetes, while 9% of the isolates showed BLAST search similarity to Basidiomycetes. The most common genera were Trichoderma and Xylaria. The most prevalent genera were Fusarium, which was detected in all the four Dendrobium species followed by Diaporthe, which was present in three Dendrobium species viz., D. chrysanthum, D. hookerianum, and D. heterocarpum. The Shannon index value of endophytic fungal communities was the highest in D. chrysanthum (2.66), while D. longicornu (1) had the highest Evenness index. The present study revealed that endophytic fungi in these orchids are an amalgam of pathogenic and beneficial fungi, which have, at the least, switched their lifestyle to asymptomatic endophyte in their host. To our knowledge, this is the first such report on the diversity of endophytic fungi in the four selected Dendrobium species from Meghalaya, India.     

沉默LIMK1抑制人结肠癌SW480细胞上皮-间质转化

目的:研究沉默LIMK1对人结肠癌SW480细胞上皮-间质转化（epithelial-mesenchymal transformation，EMT）的影响。方法:RT-PCR、Western blot、免疫荧光与免疫组化检测沉默LIMK1对EMT相关分子表达的影响。裸鼠实验检测沉默LIMK1对移植瘤生长的影响。结果:RT-PCR检测显示，沉默LIMK1可下调Vimentin和上调E-cadherin mRNA表达(P<0.05)。Western blot显示，沉默LIMK1可明显下调SW480细胞Snail及Vimentin蛋白表达和上调E-cadherin表达(P<0.05)。免疫荧光显示，LIMK1沉默细胞Snail与Vimentin阳性信号较对照组明显减弱，而E-cadherin阳性信号显著增强。裸鼠实验结果显示，沉默组肿瘤生长速度较SW480组明显减慢(P<0.05)。沉默组移植瘤瘤重（0.16±0.079）g较SW480组（0.86±0.165）g明显减少，瘤重抑制率为97.7%(P<0.05)。LIMK1沉默组移植瘤较对照组的Ki-67、Vimentin、Snail与CD34阳性表达明显减弱，而E-cadherin表达明显增加。结论:沉默LIMK1可体外抑制人结肠癌SW480细胞EMT。     

柴胡皂苷D通过抑制EMT和细胞干性抑制人结直肠癌细胞SW480的迁移和侵袭

目的:研究柴胡皂苷D（saikosaponin-D，SSD）对人结直肠癌细胞SW480迁移和侵袭能力的影响，并初步探讨SSD抑制细胞迁移和侵袭的机制。方法:MTT检测SSD对细胞增殖的影响。划痕实验和Transwell迁移实验研究SSD对细胞迁移能力的影响。Transwell侵袭实验研究SSD对细胞侵袭能力的影响。Western-blot检测SSD对上皮间质转化（epithelial mesenchymal transformation，EMT）相关蛋白（E-cadherin、N-cadherin和Vimentin）表达的影响。克隆球形成实验研究SSD对细胞干性的影响。结果:在划痕实验和Transwell迁移实验中，SSD显著抑制SW480的迁移能力（P<0.05）。在Transwell侵袭实验中，SSD显著抑制SW480的侵袭能力（P<0.05）。SSD处理后，细胞E-cadherin的表达增高，N-cadherin和Vimentin的表达降低（P<0.05），同时SSD抑制SW480细胞克隆球的形成（P<0.05）。结论:柴胡皂苷D通过抑制EMT和细胞干性抑制人结直肠癌细胞SW480的迁移和侵袭。     

柴胡皂苷D通过诱导自噬抑制人结直肠癌细胞SW480增殖的实验

目的:研究柴胡皂苷D（saikosaponin-D，SSD）对人结直肠癌细胞SW480自噬的影响，并探讨诱导的自噬对细胞增殖的影响。方法:Western-blot检测SSD对自噬相关蛋白LC3A/B和p62表达的影响，LC3翻转实验和GFP-RFP-LC3荧光实验验证自噬流的发生。Western-blot检测3-MA对SSD所诱导自噬的抑制作用，MTT和细胞计数实验研究3-MA抑制自噬后SSD对SW480细胞增殖的影响。结果:SSD能够诱导SW480细胞发生自噬，表现在LC3A/B II及LC3A/B II/I比值的增高、自噬经典底物蛋白p62的减少、LC3翻转试验阳性以及LC3荧光实验中黄色和红色荧光颗粒的增多（P＜0.05）。自噬抑制剂3-MA能够抑制SSD所诱导自噬的发生（P＜0.05），且3-MA抑制自噬后，SSD对SW480的增殖抑制效应减弱（P＜0.05），提示SSD诱导的自噬对细胞的增殖起抑制作用。结论:SSD通过诱导自噬抑制人结直肠癌细胞SW480的增殖。