BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :A major problem in the search for new cancer drug targets is that the drugs are often toxic to normal tissues and require high doses to kill tumor cells. Therefore cellular targets which appear to involve low dose responses to cancer therapy are especially interesting since they could selectively target normal tissues which are not targeted by the treatment and thus may be responsible for unpleasant side effects or may be amenable to exploitation in order to improve the therapeutic ratio. One such target, which is the subject of this review, is radiation-induced bystander effects [RIBE], which result in the observation of radiation like responses in cells which have not been irradiated. RIBE is a novel phenomenon which indicates that at low doses, cell signaling is more important than direct DNA damage. Historically, DNA has always been considered to be the target for radiation therapy. The growing realization that signaling is important opens up several important therapeutic strategies which will be discussed in this review. RIBE appears to be the result of a generalized stress response in tissues or cells which is expressed at the level of the tissue, organ or organism rather than at the level of the individual cell. The signals may be produced by all exposed cells, but the response may require a quorum of cells in order to be expressed. The major response involving low LET (x- or gamma-ray) radiation exposure discussed in the existing literature is a death response. This has many characteristics of apoptosis but may be detected in cell lines without p53 expression, although the death response is suppressed in many tumor cell lines. While a death response in unirradiated normal cells around a tumor might appear to be adverse, it can in fact be protective and remove damaged cells from the population. If harnessed correctly, it could lead to the development of new drugs aimed not at tissue destruction but at enabling homeostatic mechanisms to control tumor expansion. In this scenario, the level of harmful or beneficial response will be related to the background damage, carried by the cell population, and the genetic programme determining response to damage. This focus may be important when attempting to predict the consequences of mixed therapies involving radiation and other cytotoxic agents. In this review, our current knowledge of the mechanisms underlying the induction of bystander effects by ionizing radiation is reviewed, and the question of how bystander effects may be harnessed to produce a new generation of anti-cancer drugs aimed at stabilization of tissue homeostasis rather than tissue destruction is considered.

背景与目标： ：寻找新的癌症药物靶标的主要问题是该药物通常对正常组织有毒性，需要高剂量才能杀死肿瘤细胞。因此，细胞靶标似乎涉及对癌症治疗的低剂量反应，因此特别令人感兴趣，因为它们可以选择性地靶向未被治疗靶标的正常组织，因此可能引起令人不快的副作用，或者可能适于利用以改善治疗效果。治疗比率。辐射诱导的旁观者效应[RIBE]是本综述的主题之一，该效应导致在未辐射的细胞中观察到辐射样反应。 RIBE是一种新现象，表明在低剂量时，细胞信号传导比直接DNA损伤更为重要。从历史上看，DNA一直被认为是放射治疗的目标。人们日益认识到信号转导很重要，这开启了几种重要的治疗策略，本文将对此进行讨论。 RIBE似乎是组织或细胞中普遍的应激反应的结果，这种应激反应是在组织，器官或生物体的水平而不是单个细胞的水平表达的。信号可能由所有暴露的细胞产生，但响应可能需要一定数量的细胞才能表达。现有文献中讨论的涉及低LET（X射线或γ射线）辐射暴露的主要反应是死亡反应。这具有许多细胞凋亡特征，但尽管在许多肿瘤细胞系中死亡反应受到抑制，但在没有p53表达的细胞系中可能检测到。虽然在肿瘤周围未照射的正常细胞中的死亡反应似乎是不利的，但实际上可以起到保护作用，并从群体中清除受损的细胞。如果利用得当，它可能会导致开发新药物，其目的不是破坏组织，而是使稳态机制能够控制肿瘤的扩展。在这种情况下，有害或有益反应的水平将与细胞群体所携带的背景损伤以及决定对损伤的反应的遗传程序有关。当试图预测涉及放射线和其他细胞毒剂的混合疗法的后果时，这一重点可能很重要。在这篇综述中，我们对电离辐射诱发旁观者效应的潜在机制的现有知识进行了综述，并探讨了如何利用旁观者效应来生产旨在稳定组织稳态而不是稳定组织的新一代抗癌药物的问题。考虑组织破坏。

BACKGROUND & AIMS: BACKGROUND:Previous studies revealed increased parietal late positive potentials (LPPs) in response to spider pictures in spider phobic individuals. This study searched for basic features of fear-relevant stimuli by investigating whether schematic spider images are sufficient to evoke differential behavioral as well as differential early and late ERP responses in spider phobic, social phobic (as a clinical control group), and non-phobic control participants. METHODS:Behavioral and electrophysiological correlates of the processing of schematic spider and flower images were investigated while participants performed a color (emotional Stroop) and an object identification task. Stimuli were schematic pictures of spiders and flowers matched with respect to constituting visual elements. RESULTS:Consistent with previous studies using photographic spider pictures, spider phobic persons showed enhanced LPPs when identifying schematic spiders compared to schematic flowers. In addition, spider phobic individuals showed generally faster responses than the control groups. This effect was interpreted as evidence for an increased general behavioral hypervigilance in this anxiety disorder group. Furthermore, both phobic groups showed enhanced P100 amplitudes compared to controls, which was interpreted as evidence for an increased (cortical) hypervigilance for incoming stimuli in phobic patients in general. Finally, all groups showed faster identification of and larger N170 amplitudes in response to schematic spider than flower pictures. This may reflect either a general advantage for fear-relevant compared to neutral stimuli, or might be due to a higher level of expertise in processing schematic spiders as compared to the more artificially looking flower stimuli. CONCLUSION:Results suggest that schematic spiders are sufficient to prompt differential responses in spider-fearful and spider-non-fearful persons in late ERP components. Early ERP components, on the other hand, seem to be modified by anxiety status per se, which is consistent with recent theories on general hypervigilance in the anxiety disorder spectrum.

背景与目标： 背景：以前的研究表明，在恐惧蜘蛛的个体中，对蜘蛛图片的顶壁晚期正电位（LPPs）增加。这项研究通过调查示意性蜘蛛图像是否足以引起蜘蛛恐惧症，社交恐惧症（作为临床对照组）和非恐惧症中的差异行为以及差异化的早期和晚期ERP反应，从而寻找与恐惧相关的刺激的基本特征。控制参与者。
方法：在参与者执行颜色（情绪化的Stroop）和对象识别任务的过程中，研究了示意性蜘蛛和花朵图像处理的行为和电生理相关性。刺激是与构成视觉元素相匹配的蜘蛛和花朵的示意图。
结果：与以前使用摄影蜘蛛图片进行的研究一致，与原理图花朵相比，畏惧蜘蛛的人在识别原理图蜘蛛时显示出增强的LPP。另外，蜘蛛恐惧症个体通常显示出比对照组更快的反应。该效应被解释为该焦虑症组中一般行为过度警觉性增加的证据。此外，与对照组相比，两个恐惧组均显示出增强的P100振幅，这可以解释为总体而言，恐惧患者传入刺激的（皮质）超警觉性增加的证据。最后，所有组均显示出对蜘蛛网的响应比花卉图片更快地识别N170振幅，并具有更大的N170振幅。与中性刺激相比，这可能反映与恐惧相关的一般优势，或者可能是由于与较人为看似的花刺激相比，在处理示意性蜘蛛上的专业知识水平更高。
结论：结果表明，原理图蜘蛛足以在ERP后期的恐惧蜘蛛和非恐惧蜘蛛患者中引起差异反应。另一方面，早期的ERP组件似乎已被焦虑状态本身所改变，这与最近关于焦虑症谱系的一般超警觉的理论相一致。

BACKGROUND & AIMS: :The alkenyldiarylmethanes (ADAMs) are a unique class of non-nucleoside reverse transcriptase inhibitors that have potential value in the treatment of HIV/AIDS. However, the potential usefulness of the ADAMs is limited by the presence of metabolically labile methyl ester moieties. A series of novel ADAMs were therefore designed and synthesized in order to replace the metabolically labile methyl ester moieties of the existing ADAM lead compounds with hydrolytically stable, fused isoxazolone, isoxazole, oxazolone, or cyano substituents on the aromatic rings. The methyl ester and methoxy substituents on both of the aromatic rings in the parent compound 1 were successfully replaced with metabolically stable moieties with retention of anti-HIV activity and a general decrease in cytotoxicity.

背景与目标： ：烯基二芳基甲烷（ADAM）是一类独特的非核苷类逆转录酶抑制剂，在治疗HIV / AIDS中具有潜在价值。然而，ADAM的潜在用途受到代谢不稳定的甲基酯部分的存在的限制。因此，设计并合成了一系列新颖的ADAM，以在芳香环上用水解稳定的稠合异恶唑酮，异恶唑，恶唑酮或氰基取代基取代现有ADAM铅化合物的代谢不稳定的甲基部分。母体化合物1的两个芳香环上的甲酯和甲氧基取代基均成功地被代谢稳定的部分所取代，并保留了抗HIV活性并普遍降低了细胞毒性。

BACKGROUND & AIMS: Etoposide produces reversible inhibition of topoisomerase II, leading to cleavage of DNA, and thereby has an antitumor effect. This mechanism suggests that the longer treatment is continued, the greater the antitumor effect will be. In the present study, both therapeutic and adverse effects of long-term treatment with low-dose oral etoposide were studied in 29 patients aged > or = 65 years with non-Hodgkin's lymphoma (NHL) for whom standard chemotherapy was not effective or refractory. These patients received etoposide at a dose of 50 mg/d for as long as possible. Treatment was continued until white blood cell count decreased to < or = 2,000/microL or the platelet count decreased to < or = 5 x 10(4)/microL. According to the World Health Organization (WHO) criteria of therapeutic effects, 6 (20.7%) of the 29 patients achieved complete remission and 13 patients (44.8%) had partial remission, for a response rate of 65.5%. Adverse effects of > or = grade 3 included leukopenia in 24 patients (82.8%) and anemia in 7 (24.1%). Granulocyte colony-stimulating factor (G-CSF) was given in combination with etoposide to eight patients because of leukopenia (granulocyte count < or = 1,000/microL). In view of the excellent subjective tolerance, low incidence of serious adverse effects, and good activity, single agent oral etoposide given continuously over prolonged periods represents a useful treatment for elderly patients with NHL.

背景与目标： 依托泊苷产生对拓扑异构酶II的可逆抑制，导致DNA裂解，因此具有抗肿瘤作用。该机制表明持续的治疗时间越长，抗肿瘤作用越大。在本研究中，对29岁年龄≥65岁的非霍奇金淋巴瘤（NHL）患者进行了长期低剂量口服依托泊苷的治疗，并对其不良反应进行了研究，这些患者对于标准化疗均无效或难治。这些患者尽可能长时间接受依托泊苷50 mg / d的剂量。继续治疗直至白细胞计数降低至<或= 2,000 / microL或血小板计数降低至<或= 5 x 10（4）/ microL。根据世界卫生组织（WHO）的疗效标准，在29例患者中有6例（20.7％）完全缓解，13例（44.8％）部分缓解，缓解率为65.5％。 ≥3级的不良反应包括24例白细胞减少症（82.8％）和7例贫血（24.1％）。由于白细胞减少症（粒细胞计数<或= 1,000 / microL），与依托泊苷联合给予了粒细胞集落刺激因子（G-CSF）与依托泊苷。鉴于出色的主观耐受性，严重不良反应的发生率低和良好的活动性，长时间连续给予单剂口服依托泊苷代表了对老年NHL患者的一种有效治疗方法。

BACKGROUND & AIMS: BACKGROUND:Brain metastasis (BM) is associated with poor prognosis in patients with non-small cell lung cancer (NSCLC). Recent studies demonstrated that microRNA-330-3p (miR-330-3p) was involved in NSCLC brain metastasis (BM). However, the exact parts played by miR-330-3p in BM of NSCLC remain unknown. Discovery and development of biomarkers and elucidation of the mechanism underlying BM in NSCLC is critical for effective prophylactic interventions. Here, we evaluated the expression and biological effects of miR-330-3p in NSCLC cells and explored the underlying mechanism of miR-330-3p in promoting cell migration and invasion in NSCLC. METHODS:Stable over-expression and knockdown of miR-330-3p in NSCLC cells was constructed with lentivirus. Expression levels of miR-330-3p in NSCLC cells were quantified by quantitive real-time PCR (qRT-PCR). The effects of miR-330-3p on NSCLC cells were investigated using assays of cell viability, migration, invasion, cell cycle, apoptosis, western blotting, immunohistochemical, and immunofluorescence staining. A xenograft nude mouse model and in situ brain metastasis model were used to observe tumor growth and brain metastasis. The potential target of miR-330-3p in NSCLC cells was explored using the luciferase reporter assay, qRT-PCR, and western blotting. The miR-330-3p targets were identified using bioinformatics analysis and verified by luciferase reporter assay. The correlation between GRIA3 and DNA methyltransferase (DNMT) 1 and DNMT3A was tested by RT-PCR, western blotting, and co-immunoprecipitation (IP). RESULTS:miR-330-3p was significantly up-regulated in NSCLC cell lines. MTT assay, transwell migration, and invasion assays showed that miR-330-3p promoted the growth, migration, and invasion of NSCLC cells in vitro and induced tumor growth and metastasis in vivo. Luciferase reporter assays showed that GRIA3 was a target of miR-330-3p. qRT-PCR and western blotting exhibited that miR-330-3p promoted the growth, invasion, and migration of NSCLC cells by activating mitogen-activated protein kinase (MAPK)/extracellular-regulated protein kinases (ERK) signaling pathway. Furthermore, miR-330-3p up-regulated the total DNA methylation in NSCLC cells, and co-IP-demonstrated GRIA3 was directly related with DNMT1 and DNMT3A. CONCLUSIONS:miR-330-3p promoted the progression of NSCLC and might be a potential target for the further research of NSCLC brain metastasis.

背景与目标： 背景：脑转移（BM）与非小细胞肺癌（NSCLC）患者预后差有关。最近的研究表明，microRNA-330-3p（miR-330-3p）参与了NSCLC脑转移（BM）。但是，miR-330-3p在NSCLC的BM中所起的确切作用仍然未知。发现和开发生物标志物以及阐明NSCLC中BM的潜在机制对于有效的预防性干预至关重要。在这里，我们评估了miR-330-3p在NSCLC细胞中的表达和生物学效应，并探讨了miR-330-3p在促进NSCLC细胞迁移和侵袭中的潜在机制。
方法：用慢病毒构建稳定表达miR-330-3p的NSCLC细胞。通过定量实时PCR（qRT-PCR）定量检测NSCLC细胞中miR-330-3p的表达水平。使用细胞活力，迁移，侵袭，细胞周期，凋亡，蛋白质印迹，免疫组织化学和免疫荧光染色的方法研究了miR-330-3p对NSCLC细胞的影响。用异种移植裸鼠模型和原位脑转移模型观察肿瘤的生长和脑转移。使用荧光素酶报告基因检测，qRT-PCR和Western印迹探索了NSCLC细胞中miR-330-3p的潜在靶标。使用生物信息学分析鉴定了miR-330-3p靶标，并通过萤光素酶报告基因检测法对其进行了验证。通过RT-PCR，蛋白质印迹和免疫共沉淀（IP）测试了GRIA3与DNA甲基转移酶（DNMT）1和DNMT3A之间的相关性。
结果：miR-330-3p在NSCLC细胞系中显着上调。 MTT测定，穿孔迁移和侵袭测定显示，miR-330-3p在体外促进NSCLC细胞的生长，迁移和侵袭，并在体内诱导肿瘤生长和转移。萤光素酶报告基因检测表明GRIA3是miR-330-3p的靶标。 qRT-PCR和western blotting显示，miR-330-3p通过激活有丝分裂原激活的蛋白激酶（MAPK）/细胞外调节的蛋白激酶（ERK）信号通路，促进了NSCLC细胞的生长，侵袭和迁移。此外，miR-330-3p上调了NSCLC细胞中的总DNA甲基化，并且共同IP展示的GRIA3与DNMT1和DNMT3A直接相关。
结论：miR-330-3p促进了非小细胞肺癌的发展，可能是进一步研究非小细胞肺癌脑转移的潜在靶标。

BACKGROUND & AIMS: :Objective To evaluate the etiologies for dense vitreous hemorrhage in adults with non-traumatic and reveal management of early vitrectomy for the disease. Methods Study included 105 eyes from 105 patients. Outcome measures were etiologies of vitreous hemorrhage, formation of retinal and/or disk neovascular membrane (NVM), incidence of retinal tear and detachment, visual acuity (VA) and postoperative complications. Results Mean time between presentation and surgery was 7.1 days. The most common etiologies were retinal vein occlusion (RVO) (58.1%), retinal tear (22.9%) and retinal vasculitis (10.4%). Most RVO (77.0%) and retinal vasculitis (72.7%) eyes were associated with retinal and/or disk NVM. Retinal tear and retinal detachment was found in 24 and 48 eyes, respectively. VA improved significantly from 1/70 to 0.6 following vitrectomy. The most common postoperative complication was cataract (28.6%). Conclusion RVO, retinal tear and retinal vasculitis were the most common causes of dense vitreous hemorrhage. Early vitrectomy has a good outcome with acceptable complication rates in this setting.

背景与目标： ：目的评估非创伤成人玻璃体大出血的病因，并揭示该疾病的早期玻璃体切除术的治疗方法。方法研究包括来自105名患者的105只眼睛。结果的措施是玻璃体出血，视网膜和/或盘状新血管膜（NVM）形成，视网膜撕裂和脱离的发生率，视力（VA）和术后并发症的病因。结果从就诊到手术的平均时间为7.1天。最常见的病因是视网膜静脉阻塞（RVO）（58.1％），视网膜撕裂（22.9％）和视网膜血管炎（10.4％）。大多数RVO（77.0％）和视网膜血管炎（72.7％）眼睛与视网膜和/或椎间盘NVM相关。分别在24和48只眼中发现了视网膜撕裂和视网膜脱离。玻璃体切除术后VA从1/70显着提高至0.6。最常见的术后并发症是白内障（28.6％）。结论RVO，视网膜撕裂和视网膜血管炎是玻璃体致密性出血的最常见原因。在这种情况下，早期玻璃体切除术的结果良好，并发症发生率可以接受。

BACKGROUND & AIMS: :We recently showed that non-small cell lung carcinomas (NSCLCs) are of dismal prognosis when encompassing accelerated autophagic activity. The regulation of this abnormally functioning degradation system and its association with hypoxia and apoptosis in lung carcinoma patients is unexplored. In this study we used 115 NSCLC tissues to examine the immunohistochemical expression of four distinct molecules - the major regulator of autophagy Beclin 1, the anti-apoptotic and anti-autophagic protein Bcl-2, the pro-apoptotic and pro-autophagic protein BNIP3, and a marker of hypoxia and glucolysis, the glucose transporter Glut 1. Most cases showed reduced reactivity for Beclin 1 (62%) and Bcl-2 (82%) proteins, almost half of our sample revealed strong BNIP3 expression (57%), whereas most of the carcinomas strongly expressed Glut 1 antigen (71%). Beclin 1 expression showed no association with survival. Bcl-2 positivity was a marker of good prognosis (p = 0.04), whereas BNIP3 (p = 0.0004) and Glut 1 (p = 0.03) expression correlated with poor outcome in Stage I disease. Autophagic status was negatively associated with Bcl-2 (p = 0.0006), but positively with Glut 1 expression (p = 0.001). In conclusion, the accelerated autophagic status in NSCLC is unrelated to Beclin 1 and BNIP3 expression, but does show significant association with Bcl-2 reactivity. Furthermore, we showed important correlations between glucolysis and autophagy, guiding new pathways in future lung carcinoma research.

背景与目标： ：我们最近发现，非小细胞肺癌（NSCLC）包含加速自噬活性时预后不良。肺癌患者中这种功能异常的降解系统的调节及其与缺氧和细胞凋亡的关系尚待探索。在这项研究中，我们使用了115个非小细胞肺癌组织来检查四种不同分子的免疫组织化学表达-自噬Beclin 1的主要调节剂，抗凋亡和抗自噬蛋白Bcl-2，促凋亡和自噬蛋白BNIP3，葡萄糖转运蛋白Glut 1是缺氧和糖酵解的标志。大多数病例显示Beclin 1（62％）和Bcl-2（82％）蛋白的反应性降低，几乎一半的样本显示BNIP3表达强（57％），而大多数癌症强烈表达Glut 1抗原（71％）。 Beclin 1的表达与存活率无关。 Bcl-2阳性是预后良好的标志（p = 0.04），而BNIP3（p = 0.0004）和Glut 1（p = 0.03）的表达与I期疾病的不良预后相关。自噬状态与Bcl-2呈负相关（p = 0.0006），但与Glut 1表达呈正相关（p = 0.001）。总之，NSCLC中自噬状态的加速与Beclin 1和BNIP3的表达无关，但确实与Bcl-2的反应性显着相关。此外，我们显示了糖酵解与自噬之间的重要关联，为未来肺癌研究的新途径提供了指导。

BACKGROUND & AIMS: :The sensorimotor cortical system undergoes structural and functional changes across its lifespan. Some of these changes are physiological and parallel the normal aging process, while others might represent pathophysiological mechanisms underlying neurodegenerative disorders. In the last years, the study of possible age-related modifications in brain sensorimotor functional characteristics has been the focus of several research projects. Here we have used the transcranial magnetic stimulation (TMS)-electroencephalography (EEG) navigated co-registration to investigate the influence of physiological aging on the excitability and connectivity of the human sensorimotor cortical system. To this end, we compared the TMS-evoked EEG potentials (TEPs) collected after stimulating the dominant primary motor cortex (M1) in healthy young subjects (mean age 24.5years) with those collected in healthy older adults (mean age 67.6years). We have shown that, after stimulation of the left motor cortex, TEPs are significantly affected by physiological aging. This phenomenon has a clear spatio-temporal specificity and we speculate that normal aging per se leads to some changes in the excitability of specific cortical neural assemblies whereas other alterations could reflect compensatory mechanisms to such changes.

背景与目标： ：感觉运动皮质系统在其整个生命周期中都会发生结构和功能的变化。这些变化中的一些是生理上的并且与正常衰老过程平行，而其他一些则可能代表了神经退行性疾病的病理生理机制。近年来，对大脑感觉运动功能特征可能与年龄有关的修饰的研究一直是数个研究项目的重点。在这里，我们已使用经颅磁刺激（TMS）-脑电图（EEG）导航的共同注册，以研究生理老化对人类感觉运动皮层系统的兴奋性和连通性的影响。为此，我们比较了健康年轻受试者（平均年龄24.5岁）和健康老年人（平均年龄67.6岁）在刺激主要运动皮层（M1）后所采集的TMS诱发的脑电势（TEP）。我们已经表明，刺激左运动皮层后，TEP受生理老化的影响很大。这种现象具有明显的时空特异性，我们推测正常衰老本身会导致特定皮层神经组件兴奋性发生某些变化，而其他变化可能反映出这种变化的补偿机制。

BACKGROUND & AIMS: OBJECTIVE:Echocardiography is used for the detection of cardiac sarcoid involvement in patients with non-cardiac sarcoidosis. Little information is available regarding temporal changes in left ventricular ejection fraction (LVEF) and left ventricular end-diastolic dimension (LVDd) in non-cardiac sarcoidosis patients. METHODS AND RESULTS:Fifty-four sarcoidosis patients who received periodic follow-up with echocardiography at our institute were enrolled in this study. At the time of initial ultrasonography, 13 patients were diagnosed with cardiac sarcoid involvement. All of the remaining 41 patients with extra-cardiac sarcoidosis only had a LVEF of >50%. During the median follow-up period of 39 months, two (4.9%) of the non-cardiac sarcoidosis patients were diagnosed with cardiac sarcoid involvement; one patient showed a progressive decline in the LVEF over a short period of time. It was also found that two of 41 non-cardiac sarcoidosis patients showed declines in the LVEF of >10% per year; however, they were not diagnosed with cardiac sarcoidosis during the follow-up period. CONCLUSION:Rapid deterioration of left ventricular function may increase the suspicion of sarcoid involvement of the heart in non-cardiac sarcoidosis patients; however, we must be aware that a certain subfraction of patients may not demonstrate significant abnormalities in LVEF or LVDd on periodic echocardiographic follow-up.

背景与目标： 目的：超声心动图用于检测非心脏结节病患者的心脏结节样病变。关于非心脏结节病患者左心室射血分数（LVEF）和左心室舒张末期尺寸（LVDd）随时间变化的信息很少。
方法与结果：54例结节病患者在我院接受了定期超声心动图随访。在初次超声检查时，有13例患者被诊断出患有心脏结节样病变。其余所有41例心外结节病患者的LVEF均仅> 50％。在39个月的中位随访期内，有2名（4.9％）非心脏结节病患者被诊断出患有心脏结节病。一名患者在短时间内LVEF逐渐下降。还发现41例非心脏结节病患者中有2例的LVEF下降每年> 10％。但是，在随访期间并未诊断出他们患有心脏结节病。
结论：非心脏结节病患者左心功能的迅速恶化可能增加对心脏结节累及的怀疑。但是，我们必须意识到，在定期超声心动图随访中，患者的某些亚分类可能未显示LVEF或LVDd的明显异常。

BACKGROUND & AIMS: :Sensitizing mutations in the epidermal growth factor receptor (EGFR) predict response to EGFR tyrosine kinase inhibitors (TKIs) and both first- and second-generation TKIs are available as first-line treatment options in patients with advanced EGFR-mutant non-small cell lung cancer. Eventual resistance develops with multiple mechanisms identifiable both upon repeat biopsy and in plasma circulating tumor DNA. The T790M gatekeeper mutation is responsible for almost 60% of cases. A number of third-generation TKIs are in clinical development, and osimertinib has been approved by the US Food and Drug Administration for the treatment of patients with EGFR T790M mutant lung cancer after failure of initial EGFR kinase therapy. Resistance mechanisms are being identified to these novel agents, and the treatment landscape of EGFR-mutant lung cancer continues to evolve. The sequence of EGFR TKIs may change in the future and combination therapies targeting resistance appear highly promising.

背景与目标： ：表皮生长因子受体（EGFR）中的致敏突变预测对EGFR酪氨酸激酶抑制剂（TKIs）的反应，对于晚期EGFR突变的非小细胞患者，第一代和第二代TKI均可作为一线治疗选择肺癌。最终的耐药性会通过重复活检和血浆循环肿瘤DNA鉴定出多种机制发展。 T790M Gatekeeper突变负责将近60％的病例。许多第三代TKI正在临床开发中，奥西替尼已被美国食品和药物管理局批准用于治疗初始EGFR激酶治疗失败后的EGFR T790M突变型肺癌患者。人们已经确定了对这些新型药物的耐药机制，EGFR突变型肺癌的治疗前景也在不断发展。 EGFR TKIs的序列可能会在未来发生变化，针对耐药性的联合疗法似乎很有希望。

BACKGROUND & AIMS: :Inversin, encoded by NPHP2, is one of the 10 NPHP proteins known to be involved in nephronophthisis (an autosomal recessive cystic kidney). Although the previous reports showed that inversin played an important role in embryonic development and renal diseases, its function in cancer was not revealed clearly so far. As measured by immunohistochemical staining, inversin was highly expressed in the cytoplasm of lung cancer samples (63.4%, 161/254) compared with adjacent normal lung tissues (22.0%, 11/50, p < 0.01). Moreover, its expression was positively correlated with differentiation ( p = 0.014), tumor node metastasis staging ( p = 0.007), and lymph node metastasis ( p = 0.020). The overall survival of non-small cell lung cancer patients with inversin positive expression (45.41 ± 1.800 months) was significantly reduced compared with those with inversin negative expression (51.046 ± 2.238 months, p = 0.042). Consistently, we found that the invasion capacity of A549 cells transfected with inversin was significantly stronger than that of control cells ( p < 0.05), while inversin siRNA-treatment significantly reduced cell invasion in H1299 cells ( p < 0.05). Additionally, we demonstrated that inversin could upregulate the expression of N-cadherin, Vimentin, matrix metalloproteinase-2, and matrix metalloproteinase-9. Collectively, these results indicated that inversin might promote the tumorigenicity of lung cancer cells and serve as a novel therapeutic target of non-small cell lung cancer.

背景与目标： ：Inversin由NPHP2编码，是已知与肾小球肾病（常染色体隐性囊性肾）有关的10种NPHP蛋白之一。尽管先前的报道表明，肌钙蛋白在胚胎发育和肾脏疾病中起着重要作用，但到目前为止，其在癌症中的功能尚不清楚。通过免疫组织化学染色测定，与邻近的正常肺组织（22.0％，11/50，p <0.01）相比，转化酶在肺癌样品的细胞质中高表达（63.4％，161/254）。此外，其表达与分化（p = 0.014），肿瘤结转移分期（p = 0.007）和淋巴结转移（p = 0.020）呈正相关。转化蛋白阳性表达的非小细胞肺癌患者（45.41±1.800个月）的总生存期显着低于转化蛋白阴性表达的非小细胞肺癌患者（51.046±2.238 months，p = 0.042）。一致地，我们发现用逆转蛋白转染的A549细胞的侵袭能力明显强于对照细胞（p <0.05），而逆转酶siRNA处理显着降低了H1299细胞的侵袭能力（p <0.05）。此外，我们证明了肌钙蛋白可以上调N-钙黏着蛋白，波形蛋白，基质金属蛋白酶2和基质金属蛋白酶9的表达。总体而言，这些结果表明，肌动蛋白可能促进肺癌细胞的致瘤性，并成为非小细胞肺癌的新型治疗靶标。

BACKGROUND & AIMS: :Esophageal squamous cell carcinoma is the sixth most common cancer in the developing world. The aggressive nature of esophageal squamous cell carcinoma, its tendency for relapse, and the poor survival prospects of patients diagnosed at advanced stages, represent a pressing need for the development of new therapies for this disease. Chronic inflammation is known to have a causal link to cancer pre-disposition. Nuclear factor kappa B and signal transducer and activator of transcription 3 are transcription factors which regulate immunity and inflammation and are emerging as key regulators of tumor initiation, progression, and metastasis. Although these pro-inflammatory factors in esophageal squamous cell carcinoma have been well-characterized with reference to protein-coding targets, their functional interactions with non-coding RNAs have only recently been gaining attention. Non-coding RNAs, especially microRNAs and long non-coding RNAs demonstrate potential as biomarkers and alternative therapeutic targets. In this review, we summarize the recent literature and concepts on non-coding RNAs that are regulated by/regulate nuclear factor kappa B and signal transducer and activator of transcription 3 in esophageal cancer progression. We also discuss how these recent discoveries can pave way for future therapeutic options to treat esophageal squamous cell carcinoma.

背景与目标： ：食道鳞状细胞癌是发展中国家第六大最常见的癌症。食管鳞状细胞癌的侵略性，其复发趋势以及晚期诊断出的患者生存前景差，迫切需要开发针对该疾病的新疗法。已知慢性炎症与癌症易感性有因果关系。核因子κB和信号转导子及转录激活子3是调节免疫力和炎症的转录因子，并逐渐成为肿瘤发生，发展和转移的关键调节剂。尽管这些食管鳞状细胞癌中的促炎因子已针对蛋白质编码靶标进行了很好的表征，但它们与非编码RNA的功能相互作用只是最近才受到关注。非编码RNA，尤其是microRNA和长的非编码RNA，具有作为生物标志物和替代治疗靶标的潜力。在这篇综述中，我们总结了食管癌进展中非编码RNA的最新文献和概念，这些非编码RNA受/调节核因子κB和信号转导子及转录激活子3的调控。我们还讨论了这些最新发现如何为将来治疗食管鳞状细胞癌的治疗选择铺平道路。

BACKGROUND & AIMS: OBJECTIVES:Bevacizumab has been approved by the US Food and Drug Administration as a first-line therapy for metastatic non-small-cell lung cancer (NSCLC), in combination with carboplatin and paclitaxel. A single Latin American center experience was reviewed to determine the safety and efficacy of adding bevacizumab to first-line chemotherapy in a local population. METHODS:We retrospectively identified patients with non-squamous NSCLC treated with bevacizumab plus chemotherapy combinations as first-line chemotherapy between July 1, 2006, and January 30, 2011, at Sirio Libanes Hospital in Sao Paulo, Brazil. We collected data on patient characteristics, treatment combinations, toxicities, response to treatment, and survival. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier analysis, and prognostic factors were identified by the Cox regression model. RESULTS:A total of 56 patients were included in the final analysis (median age 62.4 years; 70% male). In 35 patients (62.5%), bevacizumab was combined with carboplatin and paclitaxel, and in 16 patients (28.6%), it was combined with pemetrexed and carboplatin. The response rate evaluated by the reference clinical team reached 74.5%, the median PFS was 5.3 months, and the median OS was 14.8 months. In multivariate analysis, use of maintenance therapy was the only predictive factor for OS (hazard ratio 6.85, 95% confidence interval 2.94-15.22). No treatment-related deaths were identified, and the overall incidence of grade 3-4 non-hematologic toxicities was 16%. CONCLUSION:Our results confirm the efficacy and safety data of bevacizumab first-line combinations for NSCLC in a Brazilian population.

背景与目标： 目的：贝伐单抗已被美国食品和药物管理局批准作为转移性非小细胞肺癌（NSCLC）与卡铂和紫杉醇联合治疗的一线治疗药物。回顾了一个拉丁美洲中心的经验，以确定在当地人群中将贝伐单抗添加到一线化疗中的安全性和有效性。
方法：我们回顾性分析了2006年7月1日至2011年1月30日期间在巴西圣保罗的Sirio Libanes医院接受贝伐单抗联合化疗联合治疗的非鳞状非小细胞肺癌的患者作为一线化疗的方法。我们收集了有关患者特征，治疗组合，毒性，治疗反应和生存率的数据。通过Kaplan-Meier分析计算总生存期（OS）和无进展生存期（PFS），并通过Cox回归模型确定预后因素。
结果：最终分析共纳入56例患者（中位年龄62.4岁；男性占70％）。贝伐珠单抗联合卡铂和紫杉醇治疗35例患者（占62.5％），培美曲塞和卡铂联合治疗16例患者（占28.6％）。参考临床团队评估的缓解率为74.5％，中位PFS为5.3个月，中位OS​​为14.8个月。在多因素分析中，维持治疗是OS的唯一预测因素（危险比6.85，95％置信区间2.94-15.22）。没有发现与治疗相关的死亡，并且3-4级非血液学毒性的总发生率为16％。
结论：我们的结果证实了贝伐单抗一线联合治疗NSCLC在巴西人群中的疗效和安全性数据。

BACKGROUND & AIMS: BACKGROUND:We modified and reconstructed a high image quality portable non-mydriatic fundus camera and compared it with the tabletop fundus camera to evaluate the efficacy of the new camera in detecting retinal diseases. METHODS:We designed and built a novel portable handheld fundus camera with telemedicine system. The image quality of fundus cameras was compared to that of existing commercial tabletop cameras by taking photographs of 364 eyes from the 254 patients. In all 800 fundus images taken by two camera types, 400 images per camera, were graded with the four image clarity classifications. RESULTS:Using the portable fundus camera, 63% (252/400) images were graded as excellent overall quality, 20.5% (82/400) were good, 11.75% (47/400) were fair, and 4.75% (19/400) were inadequate. Using the tabletop fundus camera, 70.75% (283/400) images were graded as excellent overall quality, 20.4% (51/400) were good, 13.25% (53/400) were fair, and 3.25% (13/400) were inadequate. Common retinal diseases were easily identified from fundus images obtained from the portable fundus camera. CONCLUSION:The new type of non-mydriatic portable fundus camera was qualified to have professional quality of fundus images. The revolutionary screening camera provides a foundational platform which can potentially improve the accessibility of retinal screening programmes.

背景与目标： 背景：我们修改并重建了高图像质量的便携式非散瞳眼底照相机，并将其与台式眼底照相机进行比较，以评估新照相机在检测视网膜疾病中的功效。
方法：我们设计并制造了一种新型的带有远程医疗系统的便携式手持眼底照相机。通过拍摄254名患者的364眼照片，将眼底照相机的图像质量与现有商用台式照相机的图像质量进行了比较。在两种相机类型拍摄的全部800张眼底图像中，每台相机400张图像被分为四个图像清晰度分类。
结果：使用便携式眼底照相机，将63％（252/400）的图像评为总体质量优良，20.5％（82/400）的图像质量良好，11.75％（47/400）的图像质量良好，以及4.75％（19/400）的图像质量）不足。使用台式眼底照相机，将70.75％（283/400）的图像评为总体质量优良，20.4％（51/400）的图像质量良好，13.25％（53/400）的图像质量良好，3.25％（13/400）的图像质量良好不足。从便携式眼底照相机获得的眼底图像很容易识别出常见的视网膜疾病。
结论：新型非散瞳便携式眼底照相机经鉴定具有专业的眼底图像质量。革命性的筛查摄像机提供了一个基础平台，可以潜在地改善视网膜筛查程序的可及性。