Large deformation three-dimensional image registration in image-guided radiation therapy

In this paper, we present and validate a framework, based on deformable image registration, for automatic processing of serial three-dimensional CT images used in image-guided radiation therapy. A major assumption in deformable image registration has been that, if two images are being registered, every point of one image corresponds appropriately to some point in the other. For intra-treatment images of the prostate, however, this assumption is violated by the variable presence of bowel gas. The framework presented here explicitly extends previous deformable image registration algorithms to accommodate such regions in the image for which no correspondence exists. We show how to use our registration technique as a tool for organ segmentation, and present a statistical analysis of this segmentation method, validating it by comparison with multiple human raters. We also show how the deformable registration technique can be used to determine the dosimetric effect of a given plan in the presence of non-rigid tissue motion. In addition to dose accumulation, we describe a method for estimating the biological effects of tissue motion using a linear-quadratic model. This work is described in the context of a prostate treatment protocol, but it is of general applicability.     

Murein lipoprotein is a critical outer membrane component involved in Salmonella enterica serovar typhimurium systemic infection

Lipopolysaccharide (LPS) and Braun (murein) lipoprotein (Lpp) are major components of the outer membrane of gram-negative enteric bacteria that function as potent stimulators of inflammatory and immune responses. In a previous paper, we provided evidence that two functional copies of the lipoprotein gene (lppA and lppB) located on the chromosome of Salmonella enterica serovar Typhimurium contributed to bacterial virulence. In this study, we characterized lppA and lppB single-knockout (SKO) mutants and compared them with an lpp double-knockout (DKO) mutant using in vitro and in vivo models. Compared to the lpp DKO mutant, which was nonmotile, the motility of the lpp SKO mutants was significantly increased (73 to 77%), although the level of motility did not reach the level of wild-type (WT) S. enterica serovar Typhimurium. Likewise, the cytotoxicity was also significantly increased when T84 human intestinal epithelial cells and RAW264.7 murine macrophages were infected with the lpp SKO mutants compared to the cytotoxicity when cells were infected with the lpp DKO mutant. The level of interleukin-8 (IL-8) in polarized T84 cells infected with the lppB SKO mutant was significantly higher (two- to threefold higher), reaching the level in cells infected with WT S. enterica serovar Typhimurium, than the level in host cells infected with the lppA SKO mutant. The lpp DKO mutant induced minimal levels of IL-8. Similarly, sera from mice infected with the lppB SKO mutant contained 4.5- to 10-fold-higher levels of tumor necrosis factor-alpha and IL-6; the levels of these cytokines were 1.7- to 3.0-fold greater in the lppA SKO mutant-infected mice than in animals challenged with the lpp DKO mutant. The increased cytokine levels observed with the lppB SKO mutant in mice correlated with greater tissue damage in the livers and spleens of these mice than in the organs of animals infected with the lppA SKO and lpp DKO mutants. Moreover, the lppB SKO mutant-infected mice had increased susceptibility to death. Since the lpp DKO mutant retained intact LPS, we constructed an S. enterica serovar Typhimurium triple-knockout (TKO) mutant in which the lppA and lppB genes were deleted from an existing msbB mutant (msbB encodes an enzyme required for the acylation of lipid A). Compared to the lpp DKO and msbB SKO mutants, the lpp-msbB TKO mutant was unable to induce cytotoxicity and to produce cytokines and chemokines in vitro and in vivo. These studies provided the first evidence of the relative contributions of Lpp and lipid A acylation to Salmonella pathogenesis.     

CD3AK细胞过继免疫治疗的实验研究

目的: 分析抗CD3分子的单克隆抗体 (mAb)yCD3的免疫学特性和生物学活性, 观察其激活的免疫活性细胞CD3AK体外及动物体内的抑瘤作用。方法: 用流式细胞术(FCM)测定yCD3的特异性, 以及CD3AK细胞的免疫表型和产生细胞因子的情况。用 3H -TdR法测定yCD3对淋巴细胞转化的作用; 乳酸脱氢酶法 (LDH)测定CD3AK细胞的体外细胞毒活性。建立荷瘤小鼠模型, 观察静脉注射CD3AK细胞后肿瘤生长的情况、转移灶数量和小鼠存活天数。结果: yCD3与T细胞呈特异性反应, 5μgyCD3可竞争抑制 70%的标准抗CD3抗体与细胞表面CD3分子的结合。yCD3刺激外周血淋巴细胞增殖的有效浓度为 8μg/L, 并与IL- 2、抗CD28抗体有协同作用。活化的CD3AK细胞中CD3 、CD8 和CD25 细胞增多; 产生IL- 2和IFN γ的CD3 细胞均有不同程度的增加, 在抗CD28抗体协同刺激下分别增加 3. 29和 2. 47倍。当效靶细胞比为 80∶1时, CD3AK细胞对体外肿瘤细胞杀伤的百分率为 57. 54%。分组观察荷瘤动物, CD3AK细胞治疗组的抑瘤率为 33. 17%, 对小鼠肿瘤肺转移的抑制率为39. 70%, 与LAK细胞联合治疗的疗效更显著。结论: yCD3可活化T细胞, 诱导的CD3AK细胞在体外及动物体内显示抑制肿瘤的作用, 在临床抗肿瘤过继性免疫治疗中具有重要意义。     

西北地区汉族人群HLA-A、-B、-DRB1基因座单倍型分析

目的 分析西北地区汉族群体HLA-A、-B和-DRB1基因座等位基因频率和HIA-A-B、B-DRB1和A-B-DRB1单倍型，获得单倍型频率数据。方法 采用序列特异性寡核苷酸探针反向斑点杂交技术对西北地区62个家系和101个无关个体HLA-A、-B和-DRB1基因座进行基因分型，分析HLA单倍型。结果 在西北地区汉族人群中检出15个HLA-A等位基因，28个HLA-B等位基因，13个HLA-DRB1等位基因，A02、A11、A24、B13、B15、1340、DRB1＊04、DRB1＊07、DRB1＊09和DRB1＊15基因频率较高（〉10％），A02（0．3244）、B13（0．1200）和DRB1＊15（0．1400）等位基因频率最高。分析得出HLA-A-B、B-DRB1、A-B-DRB1单倍型分别有122、147和278种，83种A-B-DRB1单倍型有至少两条以上相同的单倍型，占总单倍型数的18．44％（83／450）。A30-B13-DRB1＊07、A02-B46-DRB1＊09、A01-B37-DRB1＊10、A24-B15-DRB＊15、A02-B46-DRB1＊08、A33-B58-DRB1＊03是最常见的单倍型。结论 西北地区汉族群体HLA单倍型多态性较为丰富，等位基因频率和单倍型频率数据可用于骨髓移植供者的选择、法医学亲权鉴定以及人类学研究。     

PHARMACOKINETICS OF ATRACURIUM IN ANAESTHETIZED INFANTS AND CHILDREN

The pharmacokinetics of atracurium were studied in infants andchildren anaesthetized with isoflurane and nitrous oxide inoxygen. There were no significant differences in volume of distribution(area) (139 v. 152 ml kg^–1), clearance (5.1 v. 5.3 mlkg^–1 min^–1), T (2.1 v. 2.0 mim), or T^ß(19.1 v. 20.3 min) between children with normal hepatic andrenal function and those with moderately impaired hepatic functionpresenting for hepatic transplantation. There were significantdifferences in volume of distribution (area) (176 v. 139 mlkg^–1) and in clearance of atracurium (9.1 v.5.1 ml kg^–1min^–1) between infants and children with normal excretoryfunction. In infants the clearance of atracurium in ml m^–1min^–1 (153 v. 133) tended to be greater and the T andT^ß tended to be shorter (1.0 v. 2.0 and 13.6 v. 19.1)than in children with normal excretory function; however, thesetrends did not reach statistical significance. Plasma laudanosineconcentration was around 100 ng ml^–1 greater in patientswith liver disease than in normal children from 15–45min following a bolus of atracurium 0.5 mg kg^–1.     

老年髋部骨折患者围术期“2P-3R”营养管理模式构建

目的构建老年髋部骨折患者围术期营养管理模式,促进患者早手术、早下地、早康复。方法针对老年髋部骨折患者营养管理现状,采用课题研究型品管圈活动进行改进。经过科学循证、专家指导等,从术前、术后及家庭三个环节,骨科、营养科、家庭三个维度,人员、制度、材料设备、方法、信息五个方面,制定三大对策群组并予以实施,包括组建营养支持团队、构建营养管理策略、搭建多维信息交互平台等。结果老年髋部骨折患者首次下地时间缩短为26.7 h,平均住院日缩短为5.6 d,实现了早手术、早下地、早康复的目标。结论对老年髋部骨折患者实施个性化、全流程的序贯性营养干预具有重要意义。后续还需开展大样本多中心研究以进一步验证成效,数据自动采集与智能反馈也是今后研究重点。     

气相色谱-串联质谱法测定血清中的16种多环芳烃

目的 建立血清中16种多环芳烃的气相色谱-串联质谱测定方法。方法 血清样经甲醇沉淀蛋白,加入正己烷与二氯甲烷混合溶剂萃取,萃取物氮吹至近干后,正己烷和二氯甲烷混合溶剂复溶,取1 μl上清液进样分析。16种待测多环芳烃经DB-5色谱柱(30 m×0.25 mm,0.25 μm)分离,多反应监测模式监测,内标法定量。结果 本法在1.0 μg/L～2.0×10² μg/L范围内线性良好,方法检出限为4.20×10^-2 μg/L～0.27 μg/L,加标回收率为79.7%～108.0%,精密度为2.57%～6.76%。结论 本方法具有灵敏、快速、回收率和重复性好等优点,满足人血清中多种多环芳烃测定的要求。     

不同浓度地佐辛联合丙泊酚麻醉对无痛肠镜患者的临床研究

目的研究分析不同浓度地佐辛加丙泊酚麻醉对行无痛肠镜治疗患者苏醒质量的影响。方法选择2019年1月—2020年1月于我院行无痛肠镜治疗的80例患者为本次研究对象,将其按照随机分组的方式分为甲组和乙组,各40例,甲组予以0.05 mg/kg地佐辛+丙泊酚麻醉,乙组予以0.1 mg/kg地佐辛+丙泊酚麻醉,观察两组丙泊酚用量、苏醒时间和术中不良反应发生情况,并对数据进行分析统计。结果乙组丙泊酚用量低于甲组,且乙组苏醒时间短于甲组,差异具有统计学意义(P<0.05),乙组术中不良反应发生率为7.50%低于甲组25.00%,差异具有统计学意义(P<0.05)。结论地佐辛联合丙泊酚在无痛肠镜治疗患者的麻醉中效果显著,但0.1 mg/kg地佐辛+丙泊酚安全性更高,可有效降低丙泊酚用量,缩短苏醒时间,并降低不良反应发生率,可满足临床麻醉需求,有较高的临床应用价值。     

结直肠癌RAS、BRAF基因状态与临床病理特征的关系

目的分析中国人群结直肠癌患者中KRAS、NRAS及BRAF基因突变状态与临床病理特征之间的关系。方法回顾性分析2018年1月—2020年11月于福建省肿瘤医院接受治疗的370例结直肠癌患者的肿瘤组织标本,检测KRAS、NRAS、BRAF基因突变状态及MMR蛋白表达状态,分析基因突变状态与结直肠癌临床病理特征的关系。结果370例患者中存在KRAS基因突变155例(41.9%),NRAS基因突变19例(5.1%),BRAF基因突变40例(10.8%),其中1例患者突变类型为G469V,其他均为V600E突变。KRAS基因在女性、高中分化患者中突变率高(P<0.05)。NRAS基因突变多见于低分化、浸润型患者(P<0.05)。BRAF V600E突变在右半结肠癌、年龄小于50岁、低分化、浸润型、淋巴结及远处转移患者中的突变率高(P<0.05)。结论KRAS基因突变与性别、分化程度有关,NRAS基因突变与分化程度、肿瘤大体分类有关,BRAF基因V600E突变与肿瘤原发部位、年龄、分化程度、肿瘤大体分类、区域淋巴结及远处转移有关。对结直肠癌患者进行KRAS、NRAS及BRAF基因的检测,为了解中国患者热点基因突变分布情况和临床精准诊疗提供理论依据。     

重点部门常见典型操作时的高频接触表面

目的 明确不同部门的高频接触表面,为清洁消毒工作提供依据与指导。方法 采用直接观察法对西安市某三级甲等综合医院的消化内镜室、口腔科、血透室、手术室、检验科5个医院感染管理重点部门环境表面的接触频次进行调查,计算累积接触频次与频率。结果 5个重点部门高频接触表面均为5~9个。消化胃镜室高频接触表面频次（3.57~13.29次/操作）明显多于其他部门;血透室高频接触频次范围为0.56~3.44次/操作,为5个部门中最低者。接触频次最高的表面：消化内镜室为诊疗床（13.29次/操作）,口腔科为综合治疗台操作面板（3.64次/操作）,血透室为透析机触屏（3.44次/操作）,手术室为麻醉用电脑键盘及鼠标（8.25次/操作）,检验科为电脑键盘及鼠标（4.80次/操作）。治疗车为消化内镜室、手术室及血透室的高频接触表面。结论 因医疗诊疗操作的不同,各部门高频接触表面也不尽相同。电脑鼠标和键盘、治疗车、诊疗床、诊疗专用仪器以及操作台面在调查的各重点部门均为高频接触表面。