A Network Meta-Analysis of Efficacy and Evaluation of Safety of Subcutaneous Pegylated Interferon Beta-1a versus Other Injectable Therapies for the Treatment of Relapsing-Remitting Multiple Sclerosis

Subcutaneous pegylated interferon beta-1a (peginterferon beta-1a [PEG-IFN]) 125 μg every two or four weeks has been studied in relapsing-remitting multiple sclerosis (RRMS) patients in the pivotal Phase 3 ADVANCE trial. In the absence of direct comparative evidence, a network meta-analysis (NMA) was conducted to provide an indirect assessment of the relative efficacy, safety, and tolerability of PEG-IFN versus other injectable RRMS therapies. Systematic searches were conducted in MEDLINE, Embase, and the Cochrane Library, and conference proceedings from relevant annual symposia were hand-searched. Included studies were randomized controlled trials evaluating ≥1 first-line treatments including interferon beta-1a 30, 44, and 22 μg, interferon beta-1b, and glatiramer acetate in patients with RRMS. Studies were included based on a pre-specified protocol and extracted by a team of independent reviewers and information scientists, utilizing criteria from NICE and IQWiG. In line with ADVANCE findings, NMA results support that PEG-IFN every 2 weeks significantly reduced annualized relapse rate, and 3- and 6-month confirmed disability progression (CDP) versus placebo. There was numerical trend favoring PEG-IFN every 2 weeks versus other IFNs assessed for annualized relapse rate, and versus all other injectables for 3- and 6-month CDP (6-month CDP was significantly reduced versus IFN beta-1a 30 μg). The safety and tolerability profile of PEG-IFN beta-1a 125 μg every 2 weeks was consistent with that of other evaluated treatments. Study limitations for the NMA include variant definitions of relapse and other systematic differences across trials, assumptions that populations were sufficiently similar, and inability to perform NMA of adverse events. With similar efficacy compared to other RRMS treatments in terms of annualized relapse rate and 3- and 6-month CDP, a promising safety profile, and up to 93% reduction in number of injections (which may improve adherence), PEG-IFN every 2 weeks offers a valuable alternative treatment option for patients with RRMS.     

An Automated and Intelligent Medical Decision Support System for Brain MRI Scans Classification

A wide interest has been observed in the medical health care applications that interpret neuroimaging scans by machine learning systems. This research proposes an intelligent, automatic, accurate, and robust classification technique to classify the human brain magnetic resonance image (MRI) as normal or abnormal, to cater down the human error during identifying the diseases in brain MRIs. In this study, fast discrete wavelet transform (DWT), principal component analysis (PCA), and least squares support vector machine (LS-SVM) are used as basic components. Firstly, fast DWT is employed to extract the salient features of brain MRI, followed by PCA, which reduces the dimensions of the features. These reduced feature vectors also shrink the memory storage consumption by 99.5%. At last, an advanced classification technique based on LS-SVM is applied to brain MR image classification using reduced features. For improving the efficiency, LS-SVM is used with non-linear radial basis function (RBF) kernel. The proposed algorithm intelligently determines the optimized values of the hyper-parameters of the RBF kernel and also applied k-fold stratified cross validation to enhance the generalization of the system. The method was tested by 340 patients’ benchmark datasets of T1-weighted and T2-weighted scans. From the analysis of experimental results and performance comparisons, it is observed that the proposed medical decision support system outperformed all other modern classifiers and achieves 100% accuracy rate (specificity/sensitivity 100%/100%). Furthermore, in terms of computation time, the proposed technique is significantly faster than the recent well-known methods, and it improves the efficiency by 71%, 3%, and 4% on feature extraction stage, feature reduction stage, and classification stage, respectively. These results indicate that the proposed well-trained machine learning system has the potential to make accurate predictions about brain abnormalities from the individual subjects, therefore, it can be used as a significant tool in clinical practice.     

Altered immunodominance hierarchies of CD8+ T cells in the spleen after infection at different sites is contingent on high virus inoculum

Activated epitope-specific CD8+ T cells after virus infection can be organized into hierarchies (immunodominance), based on their ability to focus the response on few viral determinants. The mechanisms responsible for immunodominance can be multifactorial, with CD8+ T cells precursor frequencies recently highlighted as a key regulator. Employing the LCMV infection model, we demonstrate that the hierarchies were altered when comparing different sites of infection but only at high viral doses. These findings have significant implications when investigating immunity to viruses with different replication abilities that may override the influence of T cell precursor frequencies.     

Novel TNF-α converting enzyme (TACE) inhibitors as potential treatment for inflammatory diseases

Our research on hydantoin based TNF-α converting enzyme (TACE) inhibitors has led to an acetylene containing series that demonstrates sub-nanomolar potency (K(i)) as well as excellent activity in human whole blood. These studies led to the discovery of highly potent TACE inhibitors with good DMPK profiles.     

桥小脑角区脑膜瘤显微外科手术17例分析

目的:探讨桥小脑角脑膜瘤的临床表现及相应的手术治疗方案,提高显微外科手术治疗效果.方法:回顾分析我院近5年来收治的17例桥小脑角脑膜瘤患者,均采用枕下乙状窦后手术入路.结果:本组肿瘤全切率为88.3%面神经和位听神经功能大部分保留,无死亡病例.结论:术前详细的检查和完善的手术方案制订对桥小脑角区脑膜瘤的手术治疗至关重要,显微外科手术是治疗桥小脑角区脑膜瘤安全有效的方法     

Calcium chloride and gibberellic acid protect linseed (Linum usitatissimum L.) from NaCl stress by inducing antioxidative defence system and osmoprotectant accumulation

Salinity stress affects many metabolic facets of plants and induces anatomical and morphological changes resulting in reduced growth and productivity. To overcome the damaging effects of salinity, different strategies of the application of nutrients with plant hormones are being adopted. The present study was carried out with an aim to find out whether application of calcium chloride (CaCl₂) and gibberellic acid (GA₃) could alleviate the detrimental effects of salinity stress on plant metabolism. Fifteen days old plants were supplied with (1) 0 mM NaCl + 0 mg CaCl₂ kg^?1 sand + 0 M GA₃ (control, T0); (2) 0 mM NaCl + 10 mg CaCl₂ kg^?1 sand + 0 M GA₃ (T1); (3) 0 mM NaCl + 0 mg CaCl₂ kg^?1 sand + 10^?6 M GA₃ (T2); (4) 150 mM NaCl + 0 mg CaCl₂ kg^?1 sand + 0 M GA₃ (T3); (5) 150 mM NaCl + 10 mg CaCl₂ kg^?1 sand + 0 M GA₃ (T4); (6) 150 mM NaCl + 0 mg CaCl₂ kg^?1 sand + 10^?6 M GA₃ (T5); (7) 150 mM NaCl + 10 mg CaCl₂ kg^?1 sand + 10^?6 M GA₃ (T6). To assess the response of the crop to NaCl, CaCl₂ and GA₃, plants were uprooted randomly at 60 days after sowing. The presence of NaCl in the growth medium decreased all the growth and physio-biochemical parameters, except electrolyte leakage, proline (Pro) and glycine betaine (GB) content, thiobarbituric acid reactive substances (TBARS), H₂O₂ content, activities of superoxide dismutase (SOD) and catalase (CAT) and leaf Na content, which exhibited an increase of 37.6, 29.3, 366.9, 107.5, 59.1, 17.1, 28.4 and 255.2%, respectively, compared to the control plants. However, application of CaCl₂ in combination with GA₃ appears to confer greater osmoprotection by the additive role with NaCl in Pro and GB accumulation. Although the activities of antioxidant enzymes (SOD, CAT and POX) were increased by salt stress, the combined application of CaCl₂ and GA₃ to salt-stressed plants further enhanced the activities of these enzymes by 25.1, 6.7 and 47.8%, respectively, compared to plants grown with NaCl alone. The present study showed that application of CaCl₂ and GA₃ alone as well as in combination mitigated the adverse effect of salinity, but combined application of these treatments proved more effective in alleviating the adverse effects of NaCl stress.     

Genotoxic potential of copper oxide nanoparticles in human lung epithelial cells

Copper oxide nanoparticles (CuO NPs) are increasingly used in various applications. Recent studies suggest that oxidative stress may be the cause of the cytotoxicity of CuO NPs in mammalian cells. However, little is known about the genotoxicity of CuO NPs following exposure to human cells. This study was undertaken to investigate CuO NPs induced genotoxic response through p53 pathway in human pulmonary epithelial cells (A549). In addition, cytotoxicity and oxidative stress markers were also assessed. Results showed that cell viability was reduced by CuO NPs and degree of reduction was dose dependent. CuO NPs were also found to induce oxidative stress in dose-dependent manner indicated by depletion of glutathione and induction of lipid peroxidation, catalase and superoxide dismutase. The expression of Hsp70, the first tier biomarker of cellular damage was induced by CuO NPs. Further, CuO NPs up-regulated the cell cycle checkpoint protein p53 and DNA damage repair proteins Rad51 and MSH2 expression. These results demonstrate that CuO NPs possess a genotoxic potential in A549 cells which may be mediated through oxidative stress. Our short-term exposure study of high level induction of genotoxic response of CuO NPs will need to be further investigated to determine whether long-term exposure consequences may exist for CuO NPs application.     

荧光偏振技术在生命科学中的研究进展

荧光偏振技术(FP)作为一种新的检测技术已经广泛应用于生命科学的各个方面.本文对荧光偏振技术在生命科学中的研究进展做了详细的评述.介绍了荧光偏振技术的原理,评述了荧光偏振技术在生命科学中的研究热点方向.     

单药替莫唑胺与尼莫司丁联合顺铂对脑恶性胶质瘤的疗效对比观察

目的:探讨恶性脑胶质瘤手术后应用单药替莫唑胺(TMZ)方案化疗与尼莫司汀联合顺铂(ACNU+DDP)化疗的效果.方法:选取经病理证实为恶性脑胶质瘤患者60例,手术治疗后随机分为TMZ和ACNU+DDP两组,按标准方案分别给予4～6个疗程的化疗.每个化疗期间分别复查头颅MRI及肝肾功、血细胞分析,并与化疗前资料相比较,判断病情变化.结果:TMZ组有效率达为44.0%,ACNU+DDP组为14.28%,两组相差显著(P<0.05).TMZ组严重副反应发生率为16.0%,ACNU+DDP组为31.43%,两组相差显著(P<0.05).结论:TMZ比ACNU+DDP不仅能更好的改善恶性胶质瘤患者的预后,提高其生活质量,而且具有较高的安全性.