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A COMPACT NEUTRON GENERATOR FOR THE NIORT® TREATMENT OF SEVERE SOLID CANCERS 用于niort®治疗严重实体癌的紧凑型中子发生器
Pub Date : 2023-01-01 DOI: 10.18103/mra.v11i3.3799
M. Martellini
In the last four years, TheranostiCentre S.r.l., Berkion Technology LLC and ENEA have patented and fabricated a first prototype of a Compact Neutron Generator (CNG) currently under testing in the ENEA laboratories. Besides the usual applications in the field of materials irradiation, this CNG - producing neutrons of 2.45 MeV energy by using the DD fusion reaction - was conceived for the neutron irradiation of the solid cancer’s tumour bed by means of the Intra-Operative Radiotherapy (IORT) technique, the so-called neutron-IORT (nIORT®). The CNG is self-shielded and light-weight (~120 kg) making possible its remote handling by a robotic arm. Accurate Monte Carlo simulations, modelling the CNG and the “open wound” biological tissues near its irradiation window, demonstrated that the apparatus - operated at 100 kV-10 mA - supplies a neutron flux ~108 cm-2 s-1 and can deliver equivalent dose rates ~2 Gy (RBE)/min. Hence, it can administer very high dose levels in limited treatment times. This article briefly summarizes the main findings of this collaborative research study, the clinical rationales underpinning the nIORT® idea and the potential performances of the CNG for the treatment of solid cancer pathologies. Indeed, the CNG can be installed in an operating room dedicated to nIORT® treatments, without posing any environmental and safety issues. Monte Carlo simulations have been carried out by envisioning the CNG equipped with an IORT applicator, that is an applicator pipe with a tuneable diameter to be inserted in the surgical cavity. By foreseeing the clinical endpoints of the standard IORT protocols, the irradiation performances for potential nIORT® treatments - obtained with an applicator pipe of 6 cm diameter - are here reported for different regimes: from 10 up to 75 Gy (RBE), that can be administered in a single session of about 4 to 30 minutes. Besides the dose peak in the centre of the tumour bed, the almost isotropic neutrons emission allows to irradiate the surroundings side-walls of the tumour bed – usually filled by potential quiescent cancer cells (QCCs) – and therefore reducing the chances of local recurrences by improving the local control of the tumour. The rapid decrease in tissues depth of the dose profile (in few centimetres) will spare the neighbouring organs at risk from harmful radiations. Thus, the CNG apparatus developed for nIORT® applications can potentially improve the resectability rate of a given neoadjuvant cancer treatment and, generally, could satisfy all five R’s criteria of radiotherapy. Furthermore, in comparing with the current IORT techniques with electrons or low-keV X-rays, the nIORT® exploiting a high-flux neutrons beam of 2.45 MeV energy could lead to some significant clinical advantages due to its larger Linear Energy Transfer (LET, ~ 40 keV/m as average) and significantly higher Relative Biological Effectiveness (RBE 16) than all other forms of ionizing radiation.
在过去的四年里,TheranostiCentre S.r.l, Berkion Technology LLC和ENEA已经获得专利,并制造了紧凑型中子发生器(CNG)的第一个原型,目前正在ENEA实验室进行测试。除了通常在材料辐照领域的应用外,这种CNG -通过使用DD聚变反应产生2.45兆电子伏能量的中子-被设想为通过术中放射治疗(IORT)技术,即所谓的中子IORT (nIORT®),用于实体癌肿瘤床的中子辐照。CNG是自屏蔽的,重量轻(~120公斤),可以通过机械臂进行远程操作。精确的蒙特卡罗模拟,模拟了CNG和其辐照窗口附近的“开放伤口”生物组织,表明该装置在100 kV-10 mA下工作,可提供约108 cm-2 s-1的中子通量,并可提供约2 Gy (RBE)/min的等效剂量率。因此,它可以在有限的治疗时间内给予非常高的剂量。本文简要总结了该合作研究的主要发现、nIORT理念的临床基础以及CNG在治疗实体癌病理方面的潜在性能。事实上,CNG可以安装在专门用于nIORT®治疗的手术室中,而不会产生任何环境和安全问题。蒙特卡罗模拟通过设想配备IORT涂抹器的CNG进行,这是一个直径可调的涂抹管,插入手术腔中。通过预测标准IORT方案的临床终点,潜在的nIORT®治疗的照射性能(通过直径6厘米的涂药管获得)在这里报告了不同的方案:从10到75 Gy (RBE),可以在大约4到30分钟的单次治疗中进行。除了肿瘤床中心的剂量峰值外,几乎各向同性的中子发射允许照射肿瘤床周围的侧壁-通常由潜在的静止癌细胞(qcc)填充-因此通过改善肿瘤的局部控制来减少局部复发的机会。剂量剖面组织深度的迅速降低(以几厘米计)将使邻近器官免受有害辐射的危害。因此,为nIORT®应用开发的CNG设备可以潜在地提高给定新辅助癌症治疗的可切除率,并且通常可以满足放疗的所有五个R标准。此外,与目前使用电子或低keV x射线的IORT技术相比,利用2.45 MeV能量的高通量中子束的nIORT®可以带来一些显着的临床优势,因为它具有更大的线性能量传递(LET,平均约40 keV/m)和比所有其他形式的电离辐射显着更高的相对生物有效性(RBE share / 16)。
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引用次数: 0
Large Variation in Diagnosis and Treatment of Chyle Leak after Pancreatic Surgery: A Nationwide Insight 胰腺手术后乳糜漏的诊断和治疗差异很大:全国范围内的观察
Pub Date : 2023-01-01 DOI: 10.18103/mra.v11i7.1.4008
S. Rietveld, A. Latenstein, M. Besselink, J. Haverkamp, J. Haver
Background: In the current literature different diagnosis and treatment strategies for chyle leak after pancreatic surgery are described. In 2017, the International Study Group for Pancreatic Surgery defined a consensus-based definition for diagnosis. However, consensus on the optimal treatment strategy is lacking. Aim: The aim of this multicenter study is to investigate the current treatment and diagnosis of chyle leak after pancreatic surgery in clinical practice in the Netherlands to gain insight into practical applications of chyle leak. Methods: A nationwide survey about the diagnosis and treatment of chyle leak was sent to specialized dieticians and pancreatic surgeons from all 16 pancreatic centers collaborating in the Dutch Pancreatic Cancer Group. Data was quantitative processed according to thematic content analysis and by using descriptive analysis. Results: In total, 16 dieticians from 16 centers and 20 surgeons from 12 centers completed the questionnaire. Analysis showed that the International Study Group for Pancreatic Surgery-definition for chyle leak was used in clinical practice by 31% (n=11) of the respondents. The results show also large nationwide variation in treatment of chyle leak after pancreatic surgery, as well between as within centers. The most common treatment was a step-up approach of nutritional therapies (44% (n=16)), which starts with an enteral fat restricted diet enriched with medium chain fatty acids followed by total parenteral nutrition. Conclusion This study shows that the current diagnosis and treatment strategies for chyle leak after pancreatic surgery in clinical practice on a nationwide scale are different. More comparable studies are needed to define the optimal treatment strategy for chyle leak. There is need for an international multidisciplinary (sub)working group to reach consensus on the treatment strategy of chyle leak and to discuss implementation strategies for clinical practice.
背景:在目前的文献中,对胰腺手术后乳糜漏的不同诊断和治疗策略进行了描述。2017年,国际胰腺外科研究小组定义了基于共识的诊断定义。然而,对最佳治疗策略缺乏共识。目的:本多中心研究的目的是探讨荷兰临床实践中胰腺手术后乳糜漏的治疗和诊断现状,以了解乳糜漏的实际应用。方法:将一份关于乳糜漏诊断和治疗的全国性调查发送给荷兰胰腺癌组所有16个胰腺中心的专业营养师和胰腺外科医生。根据专题内容分析和描述性分析对数据进行定量处理。结果:共有16个中心的16名营养师和12个中心的20名外科医生完成了问卷调查。分析显示,31% (n=11)的应答者在临床实践中使用了国际胰腺外科研究小组对乳糜漏的定义。结果还显示,全国范围内胰腺手术后乳糜漏的治疗差异很大,中心之间和中心内部也是如此。最常见的治疗方法是营养治疗的升级方法(44% (n=16)),首先是富含中链脂肪酸的肠内脂肪限制饮食,然后是全肠外营养。结论本研究表明,目前全国范围内胰腺手术后乳糜漏的诊断和治疗策略存在差异。需要更多的可比研究来确定乳糜漏的最佳治疗策略。有必要建立一个国际多学科(子)工作组,就乳糜漏的治疗策略达成共识,并讨论临床实践的实施策略。
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引用次数: 0
Towards adaptive structuring of the lupologist’s consultation to transform the care pathway of systemic lupus erythematosus 对狼疮医师会诊的适应性结构改造系统性红斑狼疮的护理途径
Pub Date : 2023-01-01 DOI: 10.18103/mra.v11i3.3679
Systemic lupus erythematosus (SLE) is a complex autoimmune disease, which can be clinically heterogeneous in the same patient over the disease process and has an unpredictable evolution. Although its prevalence is increasing, SLE remains a rare disease with frequent extra-articular manifestations managed by multiple specialists. Among these, the internist is a key player in the overall coordination of the care pathway. The dramatic improvement in the short-term prognosis of SLE observed over the past few decades has favoured the emergence of more chronic disease-associated morbidities, especially infectious, cardiovascular and/or related to sequelae, notably renal. Thus, every lupologist is confronted with the difficulty of having to address, in an educational, individualised but also systematic way, a certain number of key items on which the short-, medium- and long-term medical future of patients who develop SLE at a relatively young age depend. In recent years, in addition to the creation of a network of reference centres and the drafting of regularly updated national therapeutic guidelines and therapeutic education programs, international consensus about the factors to consider in SLE patients has been reached, including the definition of therapeutic objectives according to a treat-to-target (T2T) strategy. However, the translation of these new objectives/paradigms in real-life has encountered a number of difficulties. As part of a multidisciplinary team involving SLE patients, we developed practical tools in the form of CHECKLISTs addressing the problems of refractory SLE (D2T), the management of comorbidities and toxicities (BASICs), and, more recently, therapeutic de-escalation with a shared medical decision (T2U). It appears that there is an opportunity to transform the care pathway of SLE patients by allowing the implementation of these tools within adaptive structuring of the consultation, which has the advantage of defining a starting point within the care pathway as a common denominator for lupologists, regardless of their specialty or where they work.
系统性红斑狼疮(SLE)是一种复杂的自身免疫性疾病,在同一患者的发病过程中可能具有临床异质性,并且具有不可预测的演变。尽管SLE的患病率正在上升,但SLE仍然是一种罕见的疾病,其常见的关节外表现由多位专家治疗。其中,内科医生在护理途径的整体协调中起着关键作用。在过去的几十年里,SLE短期预后的显著改善有利于出现更多慢性疾病相关的发病率,特别是感染性、心血管和/或与后遗症相关的疾病,尤其是肾脏疾病。因此,每个狼疮学家都面临着一个困难,必须以教育的、个性化的但也是系统的方式来解决一定数量的关键项目,这些项目取决于相对年轻的SLE患者的短期、中期和长期医疗前景。近年来,除了建立参考中心网络和起草定期更新的国家治疗指南和治疗教育计划外,国际上对SLE患者应考虑的因素也达成了共识,包括根据治疗到目标(T2T)策略定义治疗目标。然而,这些新目标/范式在现实生活中的翻译遇到了许多困难。作为涉及SLE患者的多学科团队的一部分,我们开发了以清单形式解决难治性SLE (D2T),合并症和毒性管理(BASICs)的实用工具,以及最近的共享医疗决策治疗性降级(T2U)。通过允许在适应性咨询结构中实施这些工具,似乎有机会改变SLE患者的护理途径,其优势是在护理途径中定义一个起点,作为狼疮学家的共同标准,无论他们的专业或工作地点如何。
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引用次数: 0
Measuring Social Determinant Access and Equity by Race in U.S. States 美国各州按种族衡量社会决定性准入和公平
Pub Date : 2023-01-01 DOI: 10.18103/mra.v11i2.3643
R. Hahn
The effective design, implementation, monitoring, and evaluation of state programs to reduce racial health inequities requires measures of societal resource access (e.g., education, home ownership, voting) and access inequity by race in each state. This paper proposes criteria for the selection of social determinants to assess, and ways to combine data to assess overall access and overall access inequity in states. Access and equity can be compared across geographic regions assessed. Hypotheses regarding the determinants and consequences of access and equity can be examined. Means of validating metrics are proposed. An example of analysis of access and inequity for Blacks and Whites in U.S. states yields surprising results—social determinant access and access equity are generally greatest in southern states. These metrics can be used to target and measure the effects of interventions to advance health equity for racial minority populations. The condition of state access and equity by race indicates the culmination of structural racism.
要有效地设计、实施、监测和评估各州减少种族健康不平等的项目,就需要衡量每个州的社会资源获取情况(如教育、住房所有权、投票)和获取不平等情况。本文提出了评估社会决定因素的选择标准,以及结合数据评估各州总体可及性和总体可及性不平等的方法。获取和公平可以在评估的地理区域之间进行比较。可以检查关于获取和公平的决定因素和后果的假设。提出了验证度量的方法。对美国各州黑人和白人的准入和不平等的分析得出了令人惊讶的结果——社会决定性准入和准入公平通常在南部各州最为显著。这些指标可用于确定目标并衡量促进少数种族人口健康公平的干预措施的效果。国家准入和种族平等的状况表明了结构性种族主义的高潮。
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引用次数: 0
An overview of lockdown measures, vaccination rollout and other treatment strategies used against COVID-19 in the past triennium since the start of the global pandemic in the United Kingdom 概述自英国爆发全球大流行以来,过去三年里针对COVID-19采取的封锁措施、疫苗接种和其他治疗策略
Pub Date : 2023-01-01 DOI: 10.18103/mra.v11i1.3500
Carl Paramedic
In December 2019 there was a novel outbreak in Wuhan, China where an unknown respiratory disease known as SARS-COV-2 (COVID-19) started to spread rapidly across the world. In March 2020 the World Health Organisation declared a global pandemic. Over the next few years, the United Kingdom began adapting specific lockdown measures to prevent the spread of the disease, where a vaccination programme was started in December 2020 across the country to help prevent severity and reduce the rate of infection. Since the start of the pandemic, health care professionals have continued to work on effective treatment strategies to help relieve the stress on the health systems and manage the symptoms of the disease across the nation.
2019年12月,中国武汉爆发了一场新的疫情,一种名为SARS-COV-2 (COVID-19)的未知呼吸道疾病开始在全球迅速传播。2020年3月,世界卫生组织宣布全球大流行。在接下来的几年里,英国开始调整具体的封锁措施,以防止疾病的传播,并于2020年12月在全国范围内启动了一项疫苗接种计划,以帮助预防严重程度并降低感染率。自大流行开始以来,卫生保健专业人员继续致力于制定有效的治疗战略,以帮助减轻卫生系统的压力,并在全国范围内控制疾病的症状。
{"title":"An overview of lockdown measures, vaccination rollout and other treatment strategies used against COVID-19 in the past triennium since the start of the global pandemic in the United Kingdom","authors":"Carl Paramedic","doi":"10.18103/mra.v11i1.3500","DOIUrl":"https://doi.org/10.18103/mra.v11i1.3500","url":null,"abstract":"In December 2019 there was a novel outbreak in Wuhan, China where an unknown respiratory disease known as SARS-COV-2 (COVID-19) started to spread rapidly across the world. In March 2020 the World Health Organisation declared a global pandemic. Over the next few years, the United Kingdom began adapting specific lockdown measures to prevent the spread of the disease, where a vaccination programme was started in December 2020 across the country to help prevent severity and reduce the rate of infection. Since the start of the pandemic, health care professionals have continued to work on effective treatment strategies to help relieve the stress on the health systems and manage the symptoms of the disease across the nation.","PeriodicalId":94137,"journal":{"name":"Medical research archives","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91248621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Influence of glycosylation on the development and treatment of neuroblastoma. 糖基化对神经母细胞瘤发展及治疗的影响。
Pub Date : 2023-01-01 DOI: 10.18103/mra.v11i6.3933
Robert Campbell
Neuroblastoma is a solid malignancy observed in pediatric patients that develops when neuroblasts are unable to mature, leading to unregulated proliferation and tumor formation. Neuroblastoma commonly manifests in the adrenal gland, but may also form in the neck, chest, or spinal cord. Neuroblastoma is heterogeneous and aggressive in nature, leading to high treatment failure, morbidity, and mortality rates. Lewis family glycans, as part of the Core 2 O- glycans, play a key role in neuroblastoma malignant cell behavior in MYCN-amplified cell lines. Current treatment approaches for neuroblastoma include chemotherapy, surgery, and radiation. These approaches are faced with physiological and cellular barriers, including the influence of glycosylation in cancer diseases. Studies have confirmed that the inhibition of mucin glycosylation has improved effectiveness of cytotoxic drug agents employed against solid malignancies such as with pancreatic cancer, yet little research is available regarding the influence of glycosylated proteins for other diseases. This article reviews the effect of glycosylation on the development and treatment of neuroblastoma.
神经母细胞瘤是在儿科患者中观察到的一种实体恶性肿瘤,当神经母细胞无法成熟时发展,导致不受调节的增殖和肿瘤形成。神经母细胞瘤通常表现在肾上腺,但也可能在颈部、胸部或脊髓形成。神经母细胞瘤具有异质性和侵袭性,导致高治疗失败率、发病率和死亡率。Lewis家族聚糖作为Core 2 O-聚糖的一部分,在mycn扩增细胞系中神经母细胞瘤恶性细胞行为中起关键作用。目前神经母细胞瘤的治疗方法包括化疗、手术和放疗。这些方法面临着生理和细胞障碍,包括糖基化在癌症疾病中的影响。研究证实,抑制粘蛋白糖基化可提高用于治疗实体恶性肿瘤(如胰腺癌)的细胞毒性药物的有效性,但关于糖基化蛋白对其他疾病的影响的研究很少。本文就糖基化在神经母细胞瘤的发展和治疗中的作用作一综述。
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引用次数: 0
Genetic and Biochemical Characterization of Six Lactobacillus Isolates from American Quarter Horses 美国四分之一马6株乳酸菌的遗传和生化特性
Pub Date : 2023-01-01 DOI: 10.18103/mra.v11i1.3492
Racheal Baartmans, Mary Mendoza, A. Dickey, H. Hassan
The internal cavity of equine contains symbiotic microorganisms that are collectively referred to as the gut microbiota, which interact with the host immune system from birth. The microorganisms in the gut microbiota are shaped by their interactions with the gut environment throughout the life of the host, i.e., exposure to antibiotics and diet. Lactobacilli are one of the major groups found in the gastrointestinal tracts of humans and animals. Lactobacilli are members of the lactic acid bacteria, and they help to maintain a balanced gut microbiome and stimulate the host’s immune system. In this study six equine Lactobacillus spp. were isolated from three American Quarter horses of different ages (i.e., 1-day post-weaning, 1.5-month post-weaning, and 10-year-old mature gelding). The metabolic properties that allowed the isolates to survive in the harsh environment of the gut were characterized. Thus, we evaluated their abilities to metabolize different carbohydrates and to withstand acidic pH, bile salts, antibiotics, and to inhibit pathogenic bacteria which may be encountered during their passage to the small/large intestine. We also identified the genetic elements that allow the isolates to survive and persist in the host’s gut environment by using data generated from whole genome sequencing. The data indicated that the isolates were metabolically adapted to the age of the host and the type of feed consumed. The characterized isolates are potential probiotic candidates for enhancing the gut health of equines.
马的内腔含有共生微生物,这些微生物统称为肠道微生物群,从出生起就与宿主免疫系统相互作用。肠道菌群中的微生物在宿主一生中与肠道环境的相互作用(即暴露于抗生素和饮食)形成。乳酸菌是人类和动物胃肠道中发现的主要菌群之一。乳酸菌是乳酸菌的一员,它们有助于维持肠道微生物群的平衡,并刺激宿主的免疫系统。本研究从3匹不同年龄的美国四分之一马(即断奶1天、断奶1.5个月和10岁成熟骟马)中分离出6株马乳杆菌。代谢特性使分离物能够在肠道的恶劣环境中生存。因此,我们评估了它们代谢不同碳水化合物、耐受酸性pH值、胆汁盐、抗生素以及抑制致病菌的能力,这些致病菌可能在它们进入小肠/大肠的过程中遇到。我们还通过使用全基因组测序产生的数据确定了允许分离株在宿主肠道环境中存活和持续存在的遗传元件。数据表明,这些分离株在代谢方面适应了宿主的年龄和所消耗的饲料类型。所表征的分离物是潜在的益生菌候选物,可以增强马的肠道健康。
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引用次数: 0
Identifying Eye Changes in Children and Adolescents with Congenital Heart Disease with the Aid of a Smartphone: An Observational Study 借助智能手机识别患有先天性心脏病的儿童和青少年的眼部变化:一项观察性研究
Pub Date : 2023-01-01 DOI: 10.18103/mra.v11i7.2.4003
C. Mengue, L. Pellanda, M. Parodi, M. Vilela
Background: Among congenital diseases, congenital heart disease is one of the most frequent defects, accounting for high morbidity and mortality rates. Coexistence of ocular sequelae, especially in retinal microvascularization, is frequent, and may be a marker of vascular damage and severity of underlying disease. Aims: To identify ocular anatomical repercussions in children with congenital heart diseases; to describe the prevalence of potential markers associated with retinal vessels using a smartphone. Methods: This was a cross-sectional observational study with children diagnosed with congenital heart disease treated at the Instituto de Cardiologia in Porto Alegre-RS from 4 up to (but not over) 18 years old. Results: Of a total of 218 patients assessed, 206 were included in the study. Mean age was 10.19 years +- 3.88. Uncorrected visual acuity poorer than 0.6 in at least one eye was found in 11.65% (24) of all patients. Regarding retinal findings, estimated mean arterial tortuosity was 437.79 μm, and estimated mean venous tortuosity was 336.41 μm. Taking only the cyanotic group, the arterial mean reached 557.29 μm, and the venous mean reached 401.86 (p=.001 and p=.004, respectively). In the multivariate analysis, estimated mean arterial tortuosity of cyanotic patients undergoing clinical treatment was 699.13 μm versus 489.74 μm for those without clinical treatment (p<0.001). Conclusion: Presence of retinal vascular tortuosity, especially in the arterial bed, is associated with cyanotic CHD. Identification of ocular changes, especially through an easily accessible and universal method such as the smartphone, may have diagnostic and prognostic significance.
背景:先天性心脏病是先天性疾病中最常见的缺陷之一,具有很高的发病率和死亡率。眼部后遗症的共存,尤其是视网膜微血管化,是常见的,可能是血管损伤和潜在疾病严重程度的标志。目的:探讨先天性心脏病患儿的眼部解剖反应;使用智能手机描述与视网膜血管相关的潜在标记物的患病率。方法:这是一项横断面观察研究,在波尔图阿雷格里- rs的心脏病研究所诊断为先天性心脏病的儿童,年龄从4岁到(但不超过)18岁。结果:在总共218例患者中,有206例纳入了研究。平均年龄10.19岁+- 3.88岁。11.65%(24)的患者至少有一只眼未矫正视力低于0.6。在视网膜方面,估计平均动脉扭曲度为437.79 μm,估计平均静脉扭曲度为336.41 μm。仅以紫绀组为例,动脉平均值为557.29 μm,静脉平均值为401.86 μm (p=。001和p=。004年,分别)。在多变量分析中,接受临床治疗的紫绀患者估计平均动脉扭曲度为699.13 μm,而未接受临床治疗的患者估计平均动脉扭曲度为489.74 μm (p<0.001)。结论:视网膜血管弯曲,尤其是动脉床弯曲与青紫型冠心病有关。眼部变化的识别,特别是通过智能手机等容易获得和通用的方法,可能具有诊断和预后意义。
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引用次数: 0
UCP2 Upregulation Increases Fra-1 Expression and S-phase Cell Population without Decreasing Apoptosis during Skin Cell Transformation UCP2上调可增加皮肤细胞转化过程中Fra-1的表达和s期细胞群,但不减少细胞凋亡
Pub Date : 2023-01-01 DOI: 10.18103/mra.v11i6.3938
Yunfeng Zhao, Annapoorna Sreedhar, Chunjing Zhang, Noel Jacquet
Upregulation of uncoupling protein 2 (UCP2) is considered a prosurvival mechanism for cancer cells. This prosurvival function is thought to be mediated by UCP2’s uncoupling activity which reduces the production of superoxide in the mitochondria. However, exactly how highly expressed UCP2 regulates cell proliferation, cell cycle, and cell death during the early stage of tumorigenesis has not been studied thoroughly. For this purpose, we generated UCP2 stably overexpressed JB6 Cl-41 cells (a skin cell transformation model) and performed studies to answer the above questions. Our results demonstrated that UCP2 overexpression enhanced cell proliferation, activation of the oncoprotein Fra-1, anchorage-independent growth, 3D spheroids growth, and glucose uptake during skin cell transformation. Next, our results demonstrated that UCP2 overexpression resulted in marked decreases in the proportion of the cells in the G1 phase and an increase of cells in the S phase of the cell cycle, which was accompanied by increased expression of Cyclin E and Cdk2. Lastly, UCP2 overexpression did not enhance or suppress apoptosis during skin cell transformation, as indicated by Annexin V and active caspase 3/7 staining. Taken together, these data suggest that UCP2 upregulation mainly enhances the Fra-1 oncogenic pathway which drives cell proliferation, without inhibiting apoptosis during skin cell transformation.
解偶联蛋白2 (UCP2)的上调被认为是促进癌细胞存活的机制。这种促进生存的功能被认为是由UCP2的解偶联活性介导的,它减少了线粒体中超氧化物的产生。然而,在肿瘤发生早期,高表达的UCP2究竟是如何调控细胞增殖、细胞周期和细胞死亡的,目前还没有深入的研究。为此,我们制作了UCP2稳定过表达的JB6 Cl-41细胞(一种皮肤细胞转化模型),并进行了研究来回答上述问题。我们的研究结果表明,UCP2过表达增强了细胞增殖、癌蛋白Fra-1的激活、锚定非依赖性生长、3D球体生长和皮肤细胞转化过程中的葡萄糖摄取。接下来,我们的研究结果表明,UCP2过表达导致细胞周期G1期细胞比例明显减少,S期细胞比例明显增加,同时Cyclin E和Cdk2的表达增加。最后,Annexin V和活性caspase 3/7染色显示,UCP2过表达不增强或抑制皮肤细胞转化过程中的凋亡。综上所述,这些数据表明UCP2上调主要增强了驱动细胞增殖的Fra-1致癌途径,而不抑制皮肤细胞转化过程中的凋亡。
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引用次数: 0
A Review of Factors Influencing Anxiety and Depression in Persons with Multiple Sclerosis during the COVID-19 Pandemic COVID-19大流行期间多发性硬化症患者焦虑和抑郁的影响因素综述
Pub Date : 2023-01-01 DOI: 10.18103/mra.v11i6.3964
Patricia McLaughlin, L. Odom, I. Zagon
Patients with multiple sclerosis have been subjected to extra levels of stress during the COVID-19 pandemic when they were singled out by governmental regulatory agencies as sufficiently immune-compromised persons that should be in the first group to receive the untested, new COVID-19 vaccine. The designation of these persons in such a high-risk group compounded their anxiety and depression. Early in the disease in 2020-2021, little was known about the disease, the vaccine, or whether their disease-modifying therapies for multiple sclerosis were subjecting them to more immunomodulatory suppression. This review is not comprehensive of all articles written on COVID-19 and multiple sclerosis, but selectively looks at research on COVID-19 and use of low-doses of naltrexone as treatment. Specific causes for anxiety and depression are discussed in light of evidence that suggests that the length of disease, rather than age, sex, or therapy leads to more anxiety. Low-dose naltrexone in combination with other disease-modifying therapies, or alone, reduced the perceived levels of anxiety. These data suggest that clinicians may want to prescribe low-dose naltrexone for early-stage multiple sclerosis patients.
在2019冠状病毒病大流行期间,多发性硬化症患者承受了额外的压力,因为政府监管机构将他们挑选出来,认为他们的免疫功能严重受损,应该是第一批接受未经测试的新型COVID-19疫苗的人群。将这些人列入这样一个高风险群体加剧了他们的焦虑和抑郁。在2020-2021年的疾病早期,人们对这种疾病、疫苗或多发性硬化症的疾病修饰疗法是否会使他们受到更多的免疫调节抑制知之甚少。这篇综述并没有涵盖所有关于COVID-19和多发性硬化症的文章,而是选择性地研究了COVID-19的研究和使用低剂量纳曲酮作为治疗。焦虑和抑郁的具体原因讨论的证据表明,疾病的长度,而不是年龄,性别,或治疗导致更多的焦虑。低剂量纳曲酮与其他疾病缓解疗法联合使用,或单独使用,可降低感知到的焦虑水平。这些数据表明,临床医生可能希望为早期多发性硬化症患者开低剂量纳曲酮。
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