Hydralazine and Organic Nitrates Restore Impaired Excitation-Contraction Coupling by Reducing Calcium Leak Associated with Nitroso-Redox Imbalance

Although the combined use of hydralazine and isosorbide dinitrate confers important clinical benefits in patients with heart failure, the underlying mechanism of action is still controversial. We used two models of nitroso-redox imbalance, neuronal NO synthase-deficient (NOS1^−/−) mice and spontaneously hypertensive heart failure rats, to test the hypothesis that hydralazine (HYD) alone or in combination with nitroglycerin (NTG) or isosorbide dinitrate restores Ca²⁺ cycling and contractile performance and controls superoxide production in isolated cardiomyocytes. The response to increased pacing frequency was depressed in NOS1^−/− compared with wild type myocytes. Both sarcomere length shortening and intracellular Ca²⁺ transient (Δ[Ca²⁺]_i) responses in NOS1^−/− cardiomyocytes were augmented by HYD in a dose-dependent manner. NTG alone did not affect myocyte shortening but reduced Δ[Ca²⁺]_i across the range of pacing frequencies and increased myofilament Ca²⁺ sensitivity thereby enhancing contractile efficiency. Similar results were seen in failing myocytes from the heart failure rat model. HYD alone or in combination with NTG reduced sarcoplasmic reticulum (SR) leak, improved SR Ca²⁺ reuptake, and restored SR Ca²⁺ content. HYD and NTG at low concentrations (1 μm), scavenged superoxide in isolated cardiomyocytes, whereas in cardiac homogenates, NTG inhibited xanthine oxidoreductase activity and scavenged NADPH oxidase-dependent superoxide more efficiently than HYD. Together, these results revealed that by reducing SR Ca²⁺ leak, HYD improves Ca²⁺ cycling and contractility impaired by nitroso-redox imbalance, and NTG enhanced contractile efficiency, restoring cardiac excitation-contraction coupling.     

Robust and stable feature selection by integrating ranking methods and wrapper technique in genetic data classification

High dimensional data increase the dimension of space and consequently the computational complexity and result in lower generalization. From these types of classification problems microarray data classification can be mentioned. Microarrays contain genetic and biological data which can be used to diagnose diseases including various types of cancers and tumors. Having intractable dimensions, dimension reduction process is necessary on these data. The main goal of this paper is to provide a method for dimension reduction and classification of genetic data sets. The proposed approach includes different stages. In the first stage, several feature ranking methods are fused for enhancing the robustness and stability of feature selection process. Wrapper method is combined with the proposed hybrid ranking method to embed the interaction between genes. Afterwards, the classification process is applied using support vector machine. Before feeding the data to the SVM classifier the problem of imbalance classes of data in the training phase should be overcame. The experimental results of the proposed approach on five microarray databases show that the robustness metric of the feature selection process is in the interval of [0.70, 0.88]. Also the classification accuracy is in the range of [91%, 96%].     

The Effect of Design Imbalance on the Power of the F‐test of a Variance Component in the One‐Way Random Model

The ANOVA‐based F‐test used for testing the significance of the random effect variance component is a valid test for an unbalanced one‐way random model. However, it does not have an uniform optimum property. For example, this test is not uniformly most powerful invariant (UMPI). In fact, there is no UMPI test in the unbalanced case (see Khuri , Mathew , and Sinha , 1998). The power of the F‐test depends not only on the design used, but also on the true values of the variance components. As Khuri (1996) noted, we can gain a better insight into the effect of data imbalance on the power of the F‐test using a method for modelling the power in terms of the design parameters and the variance components. In this study, generalized linear modelling (GLM) techniques are used for this purpose. It is shown that GLM, in combination with a method of generating designs with a specified degree of imbalance, is an effective way of studying the behavior of the power of the F‐test in a one‐way random model.     

2‐(2‐Nitrovinyl)furan Promotes Oxidation of Cellular Proteins,Lipids, and DNA of Male Rat Liver and Kidney

The effect of 2‐(2‐nitrovinyl)furan on the redox status of male rat liver and kidney was evaluated. Twenty male rats were randomized into four groups; group A received olive oil and groups B, C, and D rats received 12.5, 25, and 50 mg/kg bodyweight of 2‐(2‐nitrovinyl)furan intraperitoneally, daily at 24 h interval, respectively, for 14 days. 2‐(2‐Nitrovinyl)furan significantly reduced (P < 0.05) alkaline phosphatase, alanine, and aspartate aminotransferase activities in male rat liver and kidney with a corresponding increase in serum. The activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and levels of reduced glutathione/glutathione disulfide (GSSG) ratio in the liver and kidney of 2‐(2‐nitrovinyl)furan‐treated rats decreased significantly (P < 0.05). In contrast, GSSG, protein carbonyl, conjugated dienes, lipid hydroperoxides, malondialdehyde, and fragmented DNA (%) in 2‐(2‐nitrovinyl)furan‐treated rats increased significantly (P < 0.05). Overall, data from this study revealed that 2‐(2‐nitrovinyl)furan exhibited its toxic effect by suppressing or depleting the antioxidant systems.     

纳米锁阳对肝性脑病肠道菌群及免疫功能的调整

目的研究纳米中药锁阳对内毒素诱发肝硬化大鼠发生肝性脑病的肠道菌群与免疫功能的影响。方法肝硬化大鼠行小剂量内毒素腹腔注射造成肝性脑病模型。观察常态、纳米中药锁阳对肠道菌群,血清IL-2水平及血浆中血氨含量影响。结果肝性脑病大鼠血浆内毒素及血氨明显升高,正常对照组与模型组比较差异有显著性（P〈0．05）。常态锁阳治疗组与纳米锁阳治疗组血浆中血氨、内毒素均明显降低,肠道菌群失调症有明显改变。常态锁阳治疗组与自然恢复组比较差异有显著性（P〈0．05）,纳米中药治疗组与常态中药治疗组比较差异有显著性（P〈0．05）。结论高血氨是内毒素诱发肝性脑病发生的主要诱因。应用中药锁阳从调整微生态失调角度来治疗肝性脑病,取得较好疗效,纳米中药锁阳的效果更佳。     

慢性阻塞性肺疾病急性加重期患者咽部菌群与免疫指标的相关性

目的探讨慢性阻塞性肺疾病(COPD)急性加重期患者咽部菌群与免疫指标的相关性,为该类患者的治疗提供参考。方法选取2016年6月至2019年8月期间于我院就诊的125例COPD患者作为研究对象,其中急性加重期60例(急性加重组),缓解期65例(缓解组)。选取同期于我院进行健康体检者60例作为对照组。比较3组对象咽部菌群检出情况和CD3~+细胞、CD4~+细胞及CD4~+/CD8~+水平,并进行Spearman相关性分析。结果急性加重组患者咽部草绿色链球菌(33.3%)、干燥奈瑟菌(25.0%)比例及菌群多样性(4.713±0.786)显著低于缓解组和对照组(均P0.05),致病菌铜绿假单胞菌、金黄色葡萄球菌、肺炎链球菌等比例及菌群总密集度均显著高于缓解组和对照组(均P0.05)。急性加重组患者CD3~+细胞、CD4~+细胞及CD4~+/CD8~+水平均显著低于缓解组和对照组(均P0.05)。Spearman相关性分析显示,COPD急性加重期患CD3~+细胞、CD4~+细胞及CD4~+/CD8~+水平与菌群总密集度均呈负相关,与菌群多样性均呈正相关(均P0.05)。结论 COPD急性加重期患者存在明显咽部菌群失衡,可引起机体免疫状态的紊乱。     

De novo trisomy 20p characterized by array comparative genomic hybridization: Report of a novel case and review of the literature

We report on a boy with speech delay, mental retardation, motor clumsiness, hyperactivity, dysmorphic facial features, brachytelephalangy and short stature. Electrocardiogram, echocardiography, renal ultrasound, electroencephalogram, fundoscopic exam and auditory brainstem responses were all normal. Brain magnetic resonance imaging showed a left temporal arachnoid cyst and a small pineal gland cyst.     

Different matrix attachment regions flanking a transgene effectively enhance gene expression in stably transfected Chinese hamster ovary cells

We describe a female patient with developmental delay, dysmorphic features and multiple congenital anomalies who presented a normal G-banded karyotype at the 550-band resolution. Array and multiplex-ligation probe amplification (MLPA) techniques identified an unexpected large unbalanced genomic aberration: a 17.6Mb deletion of 9p associated to a 14.8 Mb duplication of 20p. The deleted 9p genes, especially CER1 and FREM1, seem to be more relevant to the phenotype than the duplicated 20p genes. This study also shows the relevance of using molecular techniques to make an accurate diagnosis in patients with dysmorphic features and multiple anomalies suggestive of chromosome aberration, even if on G-banding their karyotype appears to be normal. Fluorescence in situ hybridization (FISH) was necessary to identify a masked balanced translocation in the patient's mother, indicating the importance of associating cytogenetic and molecular techniques in clinical genetics, given the implications for patient management and genetic counseling.     

Th17/Treg失衡与肝脏免疫病理反应的研究进展

Th17细胞及Th17/Treg失衡在炎症反应、组织损伤及纤维化形成中发挥了重要作用,与多种疾病的发生发展密切相关。前炎性细胞因子可诱导T细胞分化为Th17,使Th17/Treg失衡,导致IL-17、IL-6、趋化因子等促炎性细胞因子大量分泌并有效介导中性粒细胞动员与兴奋,使得机体产生炎症反应与免疫病理反应。就Th17/Treg细胞及其失衡在肝脏免疫病理反应中的研究进展进行了综述。     

Identification of a patient with intellectual disability and de novo 3.7 Mb deletion supports the existence of a novel microdeletion syndrome in 2p14–p15

Microdeletions spanning 2p14–p15 have recently been described in two patients with developmental and speech delay and intellectual disability but no congenital malformations or severe facial dysmorphism. We report a 4-year-old boy with a de novo 3.7 Mb long deletion encompassing the region deleted in the previous cases. The patient had clinical features partly consistent with the published cases including intellectual disability, absent speech, microcephaly, long face, bulbous nasal tip and thin upper lip, but his overall clinical picture was more severe compared to the published patients. The identification of this additional patient and a detailed analysis of deletions identified in various patient cohorts and in normal individuals support the existence of a new rare microdeletion syndrome in 2p14–p15. Its critical region is in the vicinity of but clearly separate from the minimal region deleted in the well established 2p15–p16.1 microdeletion syndrome. A thorough comparison of the deletions and phenotypes indicates that multiple genes located in this region may be involved in intellectual functioning, and that some patients may show composite and more complex phenotypes due to deletions spanning both critical regions.