Estimation and reduction of the radiation dose to the fetus from external-beam radiotherapy

The appearance of a malignant disease during pregnancy is relatively rare. The use of external-beam radiation therapy is limited to non-pelvic tumors which are usually located above the diaphragm. However, supradiaphragmatic radiotherapy unavoidably exposes the fetus to secondary radiation due to head leakage, scatter from the machine and scatter produced inside the patient. This fetal exposure may be associated with an elevated risk for the development of deterministic harmful effects and/or carcinogenesis. The decision about the administration of radiotherapy in a pregnant patient is influenced by the fetal dose which must always be estimated before the patient’s treatment course. The methods employed for fetal dosimetry in external-beam radiotherapy are described in this review study. Direct dose measurements using thermoluminescent dosemeters or large ionization chambers placed on physical phantoms may be used. Monte Carlo simulations on computational phantoms may also provide accurate fetal dose calculations. The physical and/or computational phantoms need to simulate the full-scatter geometry of the pregnant patient. Typical fetal dose values attributable to radiation therapy for brain tumors, head and neck cancer, breast carcinoma and Hodgkin lymphoma at the first, second and third trimesters of gestation are presented. The effectiveness of different shielding devices for fetal dose reduction in radiotherapy is discussed. The effect of the dimensions and setup of the shielding material on the radiation dose received by the fetus is described. Moreover, practical methods for reducing the fetal dose by selecting the appropriate irradiation parameters are presented.     

四霉素与噁霉灵混配制剂对水稻立枯病的防治效果

水稻是我国第一大粮食作物,为有效防治水稻立枯病并减少化学农药的使用量,进行了农药混配制剂的筛选。通过室内不同比例的噁霉灵与四霉素混配抑菌试验及田间防治试验,筛选出能有效防治水稻立枯病的四霉素与噁霉灵混配制剂,四霉素与噁霉灵有效成分比例为0.152.5,共毒系数为139.03,增效作用明显;当田间使用剂量为33.13~39.75 g/hm2时,田间防效达到73.30%。试验结果表明,四霉素与噁霉灵按一定比例混配可以有效防治水稻立枯病,有效减少化学农药的使用量。     

Continual reassessment method for partial ordering

Summary Much of the statistical methodology underlying the experimental design of phase 1 trials in oncology is intended for studies involving a single cytotoxic agent. The goal of these studies is to estimate the maximally tolerated dose, the highest dose that can be administered with an acceptable level of toxicity. A fundamental assumption of these methods is monotonicity of the dose–toxicity curve. This is a reasonable assumption for single‐agent trials in which the administration of greater doses of the agent can be expected to produce dose‐limiting toxicities in increasing proportions of patients. When studying multiple agents, the assumption may not hold because the ordering of the toxicity probabilities could possibly be unknown for several of the available drug combinations. At the same time, some of the orderings are known and so we describe the whole situation as that of a partial ordering. In this article, we propose a new two‐dimensional dose‐finding method for multiple‐agent trials that simplifies to the continual reassessment method (CRM), introduced by O'Quigley, Pepe, and Fisher (1990, Biometrics 46 , 33–48), when the ordering is fully known. This design enables us to relax the assumption of a monotonic dose–toxicity curve. We compare our approach and some simulation results to a CRM design in which the ordering is known as well as to other suggestions for partial orders.     

Synthesis, crystal structures and magnetic properties of two bis(μ-phenoxido)dicopper(II) complexes derived from reduced Schiff base ligands

Two phenoxido bridged dinuclear Cu(II) complexes, [Cu₂(L¹)₂(NCNCN)₂] (1) and [Cu₂(L²)₂(NCNCN)₂]·2H₂O (2) have been synthesized using the tridentate reduced Schiff-base ligands 2-[1-(2-dimethylamino-ethylamino)-ethyl]-phenol (HL¹) and 2-[1-(3-methylamino-propylamino)-ethyl]-phenol (HL²), respectively. The complexes have been characterized by X-ray structural analyses and variable-temperature magnetic susceptibility measurements. Both the complexes present a diphenoxido bridging Cu₂O₂ core. The geometries around metal atoms are intermediate between trigonal bipyramid and square pyramid with the Addison parameters (τ) = 0.57 and 0.49 for 1 and 2, respectively. Within the core the Cu–O–Cu angles are 99.15° and 103.51° and average Cu–O bond distances are 2.036 and 1.978 Å for compounds 1 and 2, respectively. These differences have marked effect on the magnetic properties of two compounds. Although both are antiferromagnetically coupled, the coupling constants (J = −184.3 and −478.4 cm⁻¹ for 1 and 2, respectively) differ appreciably.     

Ambient UV-B radiation reduces PSII performance and net photosynthesis in high Arctic Salix arctica

Ambient ultraviolet-B (UV-B) radiation potentially impacts the photosynthetic performance of high Arctic plants. We conducted an UV-B exclusion experiment in a dwarf shrub heath in NE Greenland (74°N), with open control, filter control, UV-B filtering and UV-AB filtering, all in combination with leaf angle control. Two sites with natural leaf positions had ground angles of 0° (‘level site’) and 45° (‘sloping site’), while at a third site the leaves were fixed in an angle of 45° to homogenize the irradiance dose (‘fixed leaf angle site’). The photosynthetic performance of the leaves was characterized by simultaneous gas exchange and chlorophyll fluorescence measurements and the PSII performance through the growing season was investigated with fluorescence measurements. Leaf harvest towards the end of the growing season was done to determine the specific leaf area and the content of carbon, nitrogen and UV-B absorbing compounds. Compared to a 60% reduced UV-B irradiance, the ambient solar UV-B reduced net photosynthesis in Salix arctica leaves fixed in the 45° position which exposed leaves to maximum natural irradiance. Also a reduced Calvin Cycle capacity was found, i.e. the maximum rate of electron transport (J_max) and the maximum carboxylation rate of Rubisco (V_cmax), and the PSII performance showed a decreased quantum yield and increased energy dissipation. A parallel response pattern and reduced PSII performance at all three sites indicate that these responses take place in all leaves across position in the vegetation. These findings add to the evidence that the ambient solar UV-B currently is a significant stress factor for plants in high Arctic Greenland.     

Cloning and characterization of novel tumor-targeting immunocytokines based on murine IL7

We generated and characterized novel antibody-cytokine fusion proteins (“immunocytokines”) based on murine interleukin-7 (IL7), an immunomodulatory protein which has previously shown anti-cancer activity in preclinical models and whose human counterpart is currently being investigated in clinical trials. The sequential fusion of the clinical-stage antibody fragment scFv(F8), specific to a tumor-associated splice isoform of fibronectin, yielded an immunocytokine (termed “F8-mIL7”) of insufficient pharmaceutical quality and in vivo tumor targeting performance, with a striking dose dependence on tumor targeting selectivity. By contrast, a novel immunocytokine design (termed “F8-mIL7-F8”), in which two scFv moieties were fused at the N- and C-terminus of murine IL7, yielded a protein of excellent pharmaceutical quality and with improved tumor-targeting performance [tumor: blood ratio = 16:1, 24 h after injection]. Both F8-mIL7 and F8-mIL7-F8 could induce tumor growth retardation in immunocompetent mice, but were not able to eradicate F9 tumors. The combination of F8-mIL7-F8 with paclitaxel led to improved therapeutic results, which were significantly better compared to those obtained with saline treatment. The study indicates how the engineering of novel immunocytokine formats may help generate fusion proteins of acceptable pharmaceutical quality, for those immunomodulatory proteins which do not lend themselves to a direct fusion with antibody fragments.     

还原型谷胱甘肽联合多烯磷脂酰胆碱对急性药物性肝损伤患者肝功能、肝纤维化指标及血清炎性因子的影响

摘要 目的：探讨还原型谷胱甘肽联合多烯磷脂酰胆碱对急性药物性肝损伤（ADILI）患者肝功能、肝纤维化指标及血清炎性因子的影响。方法：选择2017年1月~2019年3月期间我院收治的ADILI患者100例,采用随机数字表法分为对照组和联合组,各50例。对照组给予多烯磷脂酰胆碱治疗,联合组给予还原型谷胱甘肽联合多烯磷脂酰胆碱治疗,对比两组疗效、肝功能指标[谷丙转氨酶（ALT）、谷草转氨酶（AST）、总胆红素（TBIL）和谷氨酰转肽酶（GGT）]、肝纤维化指标[层粘连蛋白（LN）、III型前胶原（PC-III）、IV型胶原（IV-C）、透明质酸酶（HA）]、血清炎性因子[白介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、白介素-2（IL-2）]及不良反应。结果：对照组的总有效率为76.00%（38/50）,联合组的总有效率为94.00%（47/50）,联合组的总有效率高于对照组（P<0.05）。治疗4周后,两组ALT、AST、TBIL、GGT、LN、PC-III、IV-C、HA、IL-2、TNF-α、IL-6水平均较治疗前下降,且联合组低于对照组（P<0.05）。两组治疗期间不良反应发生率比较无明显差异（P>0.05）。结论：在多烯磷脂酰胆碱基础上,联合还原型谷胱甘肽治疗ADILI患者,疗效较好,可改善肝功能和肝纤维化指标,减轻机体炎症反应,且安全可靠。     

Targeted therapy for gastric cancer: Molecular pathways and ongoing investigations

Gastric cancer is currently the second leading cause of worldwide cancer mortality. Ongoing collaborative sequencing efforts have highlighted recurrent somatic genomic aberrations in gastric cancer, however, despite advances in characterizing the genomic landscape, there have been few advances in patient outcomes. Prognosis remains poor with a median overall survival of 12 months for advanced disease. The improved survival with trastuzumab, and more recently ramucirumab, underscore the promise of targeted and biologic therapies and the importance of molecular tumor characterization in gastric cancer. Here we review the most frequent actionable alterations in gastric cancer and highlight ongoing clinical investigations attempting to translate biologic understanding into improved clinical outcomes.     

减低剂量去甲氧柔红霉素联合阿糖胞苷方案治疗老年急性髓细胞白血病的临床研究

目的:探讨减低剂量去甲柔红霉素联合阿糖胞苷(IA)方案治疗老年急性髓细胞白血病(AML)患者的疗效。方法:收集我院老年急性髓细胞白血病患者62例,随机分成减低剂量IA治疗组和标准剂量IA对照组,两组均实施3+7治疗方案。治疗2个疗程,比较两组不良反应和临床疗效。结果:减低剂量IA治疗组总CR率和CCR率分别为75.0%和66.7%;标准剂量IA对照组总CR率和CCR率分别为50.0%和33.3%。减低剂量IA治疗组总生存期25+月较标准剂量IA对照组生存期23+月延长。结论:对于老年急性髓细胞白血病患者,减低剂量IA治疗方案的CR率和CCR率与标准剂量IA治疗方案相比具有明显疗效优势。     

Radiation dosimetry of 18F-flurocholine PET/CT studies in prostate cancer patients

PurposeWe aimed to evaluate the Equivalent Doses (H_Ts) to highly exposed organs as well as the Effective Dose (ED) for ¹⁸F-fluorocholine PET/CT scan in the follow-up of prostate cancer patients.MethodsFifty patients were administered with ¹⁸F-fluorocholine. The activities in organs with the highest uptake were derived by region-of-interest (ROI) analysis. OLINDA/EXM1.0 and Impact software were used to assess ED for the administered ¹⁸F-fluorocholine and CT scan, respectively, and the ¹⁸F-fluorocholine and CT-scan EDs summed to yield the total ED for the PET/CT procedure.ResultsThe calculated ¹⁸F-fluorocholine and CT scans EDs based on ICRP Publication 103 were 5.2 mSv/300 MBq and 6.7 mSv, respectively. The ¹⁸F-fluorocholine H_Ts to the liver, kidneys, spleen and pancreas were about threefold higher than those from the CT, which contributed a greater proportion of the total ED than the ¹⁸F-fluorocholine did.ConclusionsFor ¹⁸F-fluorocholine PET/CT procedures, about 40% of the ED is contributed by administered ¹⁸F-fluorocholine and 60% by the CT scan. The kidneys and liver were the highly exposed organs. Considering the large number of diagnostic procedures oncology patients undergo, radiation dosimetry is important in relation to the stochastic risk of such procedures.