An Evidence-Based Review of Total Body Irradiation

The purpose of this literature review is to investigate clinical treatment methods of total body irradiation within the context of a clinical department adopting a paediatric cohort with no existing technique. An extensive review of the literature was conducted using PubMed, Science Direct, Google Scholar, and Clinicians Knowledge Network. Articles were limited to nonhelical tomotherapy, nonparticle therapies, and those using hyperfractionated regimes. Total marrow irradiation was excluded because of national treatment and trial limitations. Of the numerous patient positioning methods present within the literature, the most comfortable and reproducible positioning methods for total body irradiation include both supine and the supine and/or prone combination. These positions increased stability and patient comfort during treatment, while also facilitating computed tomography data acquisition at the simulation stage. Ideally, dose calculations should be performed using a three-dimensional treatment planning system and quality assurance procedures that include in vivo dosimetry measurements. The available literature also suggests inhomogeneity correction factors and intensity modulation are superior to conventional open field techniques and should be implemented within developing protocols. Dynamic machine dose modulation is suggested to reduce department impact, removing the need for tissue compensators and accessory shielding devices, while providing significant improvements to treatment time and dose accuracy. Further long-term survival and intensity modulation studies are warranted, including direct comparisons of both dose modulation and treatment efficiency.     

Ex Vivo Radiation Leads to Opposing Neurite Growth in Whole Ganglia vs Dissociated Cultured Pelvic Neurons

BackgroundProstatic radiation therapy (RT) often causes erectile dysfunction (ED) and the mechanisms governing RT-induced ED are unclear with a lack of therapeutic strategies.AimTo determine the effects of ex vivo RT on major pelvic ganglion (MPG) neuron survival, and neurite growth in whole vs dissociated culture.MethodsMPGs were removed and irradiated (0 or 8 Gy) from male Sprague Dawley rats. For dissociated culture, MPG neurons were digested in collagenase/dispase and cultured on coverslips. Immunofluorescent staining for beta-tubulin III (TUBB3; neuron marker), neuronal nitric oxide synthase (nNOS; nitrergic marker), tyrosine hydroxylase (TH; sympathetic marker), and terminal deoxynucleotidyl transferase dUTP nick end labeling assessed neurite length, branching, autonomic neuron density, and apoptosis. For whole organ culture, MPGs were grown in Matrigel. Gene expression of apoptotic markers (caspase 1, 3), TUBB3, nNOS, TH, and Schwann cells (Sox10, Krox20, glial fibrillary acid protein) was measured in whole organ cultured MPGs by quantitative polymerase chain reaction.OutcomesAfter 72 hours, neurite length, branching, autonomic neuron density, and apoptosis were assessed, and gene expression was measured.ResultsRT increased apoptosis in dissociated neurons measured by terminal deoxynucleotidyl transferase dUTP nick end labeling (P < .001) and whole MPG culture via upregulation of caspase 3 gene expression (P < .05). Nitrergic neurons were markedly decreased in irradiated dissociated culture (P < .05), while nNOS gene expression was upregulated in irradiated whole organ culture (P < .05). The proportion of dissociated sympathetic neurons and whole organ TH gene expression remained unchanged after RT. Interestingly, RT dissociated neurites were 22% shorter than controls, while RT whole organ neurites were 15% longer than controls (P < .01). MPG Schwann cells markers (Sox10, Krox20) were elevated after RT in whole organ culture.Clinical TranslationProstatic RT leads to increased neuronal cell death and less erectogenic nitrergic neurons contributing to ED.Strengths & LimitationsThe advantages of dissociated neuron culture include distinct neurites which are easily measured for apoptosis, length/branching, and specific neuron types. In contrast, whole MPG culture is advantageous as it contains all the supporting cells present in vivo.ConclusionThe 2 different culture methods demonstrated opposing neurite growth after RT indicating the importance of supporting cell network to promote pelvic neuron neuritogenesis and survival following RT.Randolph JT, Pak ES, Koontz BF, et al. Ex Vivo Radiation Leads to Opposing Neurite Growth in Whole Ganglia vs Dissociated Cultured Pelvic Neurons. J Sex Med 2020;17:1423–1433.     

艾尔巴韦/格拉瑞韦治疗慢性丙型肝炎患者疗效初步观察

目的 初步探讨应用艾尔巴韦/格拉瑞韦治疗慢性丙型肝炎(CHC)患者的疗效。方法 2017年3月~2018年3月仙桃市第一人民医院感染病科收治的CHC患者82例,被随机分为对照组41例和观察组41例,分别给予聚乙二醇干扰素-α联合利巴韦林治疗和艾尔巴韦/格拉瑞韦治疗,两组均连续治疗24周。采用RT- PCR法检测血清 HCV RNA,采用全基因序列测定法行病毒基因分型。比较两组早期病毒学应答(EVR)、治疗结束时病毒学应答(ETVR)和持续病毒学应答(SVR)。结果 在治疗结束时,观察组血清丙氨酸氨基转移酶(ALT)水平为(47.9±19.7)U/L,显著低于对照组【(63.5±21.2)U/L,P<0.05】,天冬氨酸氨基转移酶(AST)水平为(55.5±22.3)U/L,显著低于对照组【(81.3±25.8)U/L,P<0.05】;观察组EVR、ETVR和SVR分别为48.8%、63.4%和70.7%,与对照组的41.5%、53.7%和65.8%比,无统计学差异(P>0.05);18例观察组非HCV Ⅰ型感染者EVR、ETVR和SVR分别为88.9%、94.4%和88.9%,显著高于同组23例HCV Ⅰ型感染者(分别为52.2%、60.9%和52.2%, P<0.05),而与对照组15例非HCV Ⅰ型感染者比,无统计学差异(分别为86.7%、93.3%和73.3%, P>0.05);观察组SVR₁₂为87.8%(36/41),显著高于对照组的73.2%(30/41,P<0.05)。结论 应用直接抗病毒(DAA)药物艾尔巴韦/格拉瑞韦治疗CHC患者近期疗效达到,但远期疗效似优于标准治疗方案, 值得临床进一步验证。     

成人Still病诊疗进展

【摘要】 成人Still病是一类病因未明的全身炎症性疾病，临床表现多样，其诊断和治疗存在一定困难。近年来发现，血红素加氧酶1、钙网蛋白、炎症细胞因子、糖基化终末产物等新型标志物可对成人Still病的活动程度和严重程度进行全面评估，而新研发的生物制剂如肿瘤坏死因子抑制剂、白细胞介素1（IL-1）抑制剂、IL-6抑制剂、重组IL-18结合蛋白也有望用于治疗。本文主要综述成人Still病的诊断和治疗进展。     

放射性心脏损伤动物模型相关实验研究进展

当利用放射线对胸部恶性肿瘤进行治疗时，位于纵隔的心脏会不可幸免受到照射，从而诱发放射性心脏损伤（radiation-induced heart disease, RIHD）。随着手术以及放化疗技术的提升，肿瘤患者生存时间得到延长，使得RIHD这一放疗远期并发症被越来越多的报道。因此，学者们对于RIHD的研究逐渐升温。目前国内外学者关于该疾病尚未形成统一的认识，临床上缺乏有效阻止其发生的方法。动物模型研究可为临床该疾病治疗及预防提供可靠证据，为此本文回顾分析近年来放射性心脏损伤动物模型实验研究情况，旨在为后续实验开展及临床应用提供参考。     

外泌体在血液肿瘤微环境中的作用及其诊治意义

外泌体是细胞外囊泡的一类主要成分，是正常生理情况下组织细胞间信号传递的重要介质；在多种血液肿瘤研究中发现外泌体是骨髓微环境各成分间相互作用的关键载体，由于其广泛存在并含有特定的核酸、蛋白等分子，外泌体被作为潜在的生物标志物和治疗靶点/载体，在血液肿瘤诊治中的重要性近年正逐步受到关注。     

Frustration Intolerance Beliefs: Their Relationship with Depression, Anxiety, and Anger, in a Clinical Population

Beliefs regarding the toleration of frustration and discomfort are often described as underlying psychological disturbance, and represent a fundamental concept in Rational Emotive Behavior Therapy (REBT). Nevertheless, there has been little systematic analysis of the content of these beliefs, which are often treated as a unidimensional construct. This paper investigates the relationship between a multidimensional Frustration Discomfort Scale (FDS) and measures of depressed mood, anxiety, and anger, in a clinical population. Results indicated that FDS sub-scales were differentially related to specific emotions, independent of self-esteem and negative affect. The entitlement sub-scale was uniquely associated with anger, discomfort intolerance with depressed mood, and emotional intolerance with anxiety. These results supported the validity of the FDS, the importance of distinguishing between frustration intolerance dimensions, and of separating these beliefs from those related to self-worth.Copies of the Frustration Discomfort Scale are available from the author on request