• 【异硫氰酸根合苄基-DTPA衍生的单克隆抗肌球蛋白fab用于增强体内靶标定位的用途。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Khaw BA,Gansow O,Brechbiel MW,O'Donnell SM,Nossiff N
    BACKGROUND & AIMS: :Monoclonal antimyosin Fab (AM-Fab) was radiolabeled with 111In via a new bifunctional chelating agent, isothiocyanatobenzyl-DTPA (SCN-DTPA), and used to visualize acute reperfused experimental myocardial infarction. Antibody localization was compared to 201Tl (0.6 mCi) distribution in nine animals. Each animal was injected intravenously with 0.5 mCi of 111In-SCN-DTPA AM-Fab preparations (Prep 1 [n = 5] and 2 [n = 4]). The biodistribution was compared to that of 111In-labeled conventional bicyclic anhydride DTPA-AM-Fab (n = 5). 111In-SCN-DTPA AM-Fab Prep 1 (lowest specific activity) showed highest specific target localization (31.6 +/- 3.5, MEAN infarct[0-20% Tl-201] to normal ration +/- SE) and lowest hepatic sequestration (0.0108 +/- 0.002% ID/g). Prep 2 showed similar infarct localization (18.4 +/- 1.2) to control 111In-DTPA AM-Fab (16.9 +/- 1.1), but had higher hepatic activity (0.0326 +/- 0.014 and 0.0267 +/- 0.006 respectively). This difference in in vivo localization occurred despite the lack of changes in in vitro immunoreactivities of the AM-Fab preparations. The enhanced target localization with minimal hepatic activity may permit a more sensitive diagnostic application of 111In-labeled AM-Fab in future clinical studies.
    背景与目标: :单克隆抗肌球蛋白Fab(AM-Fab)通过新型双功能螯合剂异硫氰酸根合苄基-DTPA(SCN-DTPA)进行了放射性标记,并用于可视化急性再灌注实验性心肌梗塞。将抗体的定位与9只动物中201T1(0.6 mCi)的分布进行了比较。给每只动物静脉内注射0.5 mCi的111In-SCN-DTPA AM-Fab制剂(预后1 [n = 5]和2 [n = 4])。将生物分布与111In标记的常规双环酸酐DTPA-AM-Fab(n = 5)进行了比较。 111In-SCN-DTPA AM-Fab Prep 1(最低活性)显示最高特异性靶标定位(31.6 /-3.5,MEAN梗死[0-20%Tl-201]到正常剂量/-SE)和最低的肝螯合(0.0108) /-0.002%ID / g)。制剂2显示出与对照111In-DTPA AM-Fab(16.9 / -1.1)相似的梗塞定位(18.4 / -1.2),但是具有更高的肝活性(分别为0.0326 / -0.014和0.0267 / -0.006)。尽管AM-Fab制剂的体外免疫反应性没有变化,但仍存在体内定位的差异。具有最小的肝活性的增强的靶标定位可以允许在未来的临床研究中更敏感地将111In标记的AM-Fab应用于诊断。
  • 【神经性厌食症青少年的增强认知行为疗法:家庭疗法的替代方案?】 复制标题 收藏 收藏
    DOI:10.1016/j.brat.2012.09.008 复制DOI
    作者列表:Dalle Grave R,Calugi S,Doll HA,Fairburn CG
    BACKGROUND & AIMS: :A specific form of family therapy (family-based treatment) is the leading treatment for adolescents with anorexia nervosa. As this treatment has certain limitations, alternative approaches are needed. "Enhanced" cognitive behaviour therapy (CBT-E) is a potential candidate given its utility as a treatment for adults with eating disorder psychopathology. The aim of the present study was to establish, in a representative cohort of patients with marked anorexia nervosa, the immediate and longer term outcome following CBT-E. Forty-nine adolescent patients were recruited from consecutive referrals to a community-based eating disorder clinic. Each was offered 40 sessions of CBT-E over 40 weeks from a single therapist. Two-thirds completed the full treatment with no additional input. In these patients there was a substantial increase in weight together with a marked decrease in eating disorder psychopathology. Over the 60-week post-treatment follow-up period there was little change despite minimal subsequent treatment. These findings suggest that CBT-E may prove to be a cost-effective alternative to family-based treatment.
    背景与目标: :一种特殊形式的家庭治疗(基于家庭的治疗)是神经性厌食症青少年的主要治疗方法。由于这种治疗有一定的局限性,因此需要其他方法。鉴于“增强型”认知行为疗法(CBT-E)可用于患有饮食失调症的心理病理学成年人,因此是一种潜在的候选药物。本研究的目的是在具有明显神经性厌食症的患者的代表性队列中建立CBT-E术后的近期和长期预后。从连续转诊到社区饮食失调诊所招募了49名青少年患者。一位治疗师在40周内为每位患者提供了40次CBT-E疗程。三分之二的人完成了全部治疗,没有其他投入。在这些患者中,体重显着增加,而进食障碍的精神病理学显着下降。在治疗后的60周随访期内,尽管后续治疗最少,但变化不大。这些发现表明,CBT-E可能被证明是替代基于家庭的治疗的一种经济有效的选择。
  • 【在一项1型糖尿病患者的随机试验中测试的分散注射策略的结果是,门冬胰岛素的吸收得到增强。】 复制标题 收藏 收藏
    DOI:10.2337/dc12-1319 复制DOI
    作者列表:Mader JK,Birngruber T,Korsatko S,Deller S,Köhler G,Boysen S,Augustin T,Mautner SI,Sinner F,Pieber TR,AP@home Consortium.
    BACKGROUND & AIMS: OBJECTIVE:We investigated the impact of two different injection strategies on the pharmacokinetics and pharmacodynamics of insulin aspart in vivo in an open-label, two-period crossover study and verified changes in the surface-to-volume ratio ex vivo. RESEARCH DESIGN AND METHODS:Before the clinical trial, insulin aspart was injected ex vivo into explanted human abdominal skin flaps. The surface-to-volume ratio of the subcutaneous insulin depot was assessed by microfocus computed tomography that compared 1 bolus of 18 IU with 9 dispersed boluses of 2 IU. These two injection strategies were then tested in vivo, in 12 C-peptide-negative type 1 diabetic patients in a euglycemic glucose clamp (glucose target 5.5 ± 1.1 mmol/L) for 8 h after the first insulin administration. RESULTS:The ex vivo experiment showed a 1.8-fold higher mean surface-to-volume ratio for the dispersed injection strategy. The maximum glucose infusion rates (GIR) were similar for the two strategies (10 ± 4 vs. 9 ± 4; P = 0.5); however, times to reach maximum GIR and 50% and 10% of the maximum GIR were significantly reduced by using the 9 × 2 IU strategy (68 ± 33 vs. 127 ± 93 min; P = 0.01; 38 ± 9 vs. 49 ± 16 min; P < 0.01; 23 ± 6 vs. 30 ± 10 min; P < 0.05). For 9 × 2 IU, the area under the GIR curve was greater during the first 60 min (219 ± 89 vs. 137 ± 75; P < 0.01) and halved until maximum GIR (242 ± 183 vs. 501 ± 396; P < 0.01); however, it was similar across the whole study period (1,361 ± 469 vs. 1,565 ± 527; P = 0.08). CONCLUSIONS:A dispersed insulin injection strategy enhanced the effect of a fast-acting insulin analog. The increased surface-to-volume ratio of the subcutaneous insulin depot can facilitate insulin absorption into the vascular system.
    背景与目标: 目的:我们在开放标签,两期交叉研究中研究了两种不同的注射策略对体内门冬胰岛素的药代动力学和药效学的影响,并验证了离体表面积与体积比的变化。
    研究设计和方法:在临床试验之前,将门冬胰岛素离体注射到植入的人腹部皮肤皮瓣中。皮下胰岛素贮存库的表面体积比是通过微焦点计算机断层扫描技术评估的,该技术比较了1个大剂量的18 IU与9个分散的大剂量的2 IU。然后在首次胰岛素给药后的正常血糖葡萄糖钳位(葡萄糖靶标5.5±1.1 mmol / L)中,在12名C肽阴性1型糖尿病患者体内测试了这两种注射策略。
    结果:离体实验显示,分散注射策略的平均表面体积比高1.8倍。两种策略的最大葡萄糖输注速率(GIR)相似(10±4 vs. 9±4; P = 0.5);但是,通过使用9×2 IU策略,达到最大GIR以及达到最大GIR的时间分别减少了50%和10%(68±33 vs. 127±93 min; P = 0.01; 38±9 vs. 49± 16分钟; P <0.01; 23±6 vs. 30±10分钟; P <0.05)。对于9×2 IU,在最初的60分钟内GIR曲线下的面积更大(219±89对137±75; P <0.01),并且减半直到最大GIR(242±183对501±396对; P < 0.01);但是,在整个研究期间,情况相似(1,361±469对1,565±527; P = 0.08)。
    结论:分散胰岛素注射策略增强了速效胰岛素类似物的作用。皮下胰岛素贮存库增加的表面积与体积之比可以促进胰岛素吸收进入血管系统。
  • 【具有固有雌激素样基因反式激活潜能的人类乳腺癌细胞中非酚类雄激素代谢物的形成增强:一种独特的代谢模式。】 复制标题 收藏 收藏
    DOI:10.1677/joe.1.06407 复制DOI
    作者列表:Pérez-Palacios G,Santillán R,García-Becerra R,Borja-Cacho E,Larrea F,Damián-Matsumura P,González L,Lemus AE
    BACKGROUND & AIMS: :Breast cancer is a sex steroid hormone-dependent malignant neoplasia. The role of oestradiol in this malignancy has been well documented; however, the involvement of androgens has remained controversial. To determine the role of non-phenolic androgen metabolites in human breast cancer, we studied the metabolism of [(14)C] testosterone and [(14)C] androstenedione in oestrogen-dependent MCF-7 cells and non-oestrogen-dependent MDA-MB 231 cells, at different substrate concentrations (1-10 muM) and time periods (30 min-48 h). Cultured non-oestrogen-dependent HeLa and yeast cells served as controls. Metabolites were identified and quantified by reverse isotope dilution. A distinctive pattern of androgen metabolism was identified in MCF-7 cells, being the 5alpha-androstane-3alpha,17beta-diol (3alpha,5alpha-diol) and its 3beta epimer (3beta,5alpha-diol), the major conversion products of testosterone (48.3%), with 5alpha-dihydrotestosterone as intermediary. The formation of 3alpha,5alpha-diol and 3beta,5alpha-diol (diols) was substrate concentration- and time-dependent, and abolished by finasteride. In contrast, very little of any diol formation was observed in MDA-MB 231, HeLa and yeast cell incubations. Additional enzyme gene expression studies revealed an overexpression of 5alpha-steroid reductase type-1 in MCF-7 cells, as compared with MDA-MB 231 cells. The oestrogen-like activities of diols were assessed in HeLa cells co-transfected with expression vectors for alpha or beta subtypes of the human oestrogen receptor (hER) genes and for an oestrogen-responsive reporter gene. The results show that 3beta, 5alpha-diol and to a lesser extent 3alpha,5alpha-diol bind with high relative affinity to hERalpha and hERbeta. Both diols induced hER-mediated reporter gene transactivation in a dose-response manner, similar to that induced by oestradiol, though with lower potency, an effect that was abolished by ICI-182 780. Furthermore, 3beta,5alpha-diol and to lesser extent 3alpha,5alpha-diol induced MCF-7 cell proliferation. The overall results demonstrated that MCF-7 cells exhibit enhanced expression and activity of androgen-metabolising enzymes, leading to rapid and large diol formation, and provide evidence that these androgen metabolites exert a potent oestrogen-agonistic effect, at genomic level, in oestrogen-dependent breast cancer cells. The data suggest that diols may act as in situ intracrine factors in breast cancer and that its formation can be pharmacologically inhibited.
    背景与目标: :乳腺癌是性激素依赖的恶性肿瘤。雌二醇在这种恶性肿瘤中的作用已被充分证明。然而,雄激素的参与仍存在争议。为了确定非酚类雄激素代谢物在人类乳腺癌中的作用,我们研究了雌激素依赖性MCF-7细胞和非雌激素依赖性MDA中[(14)C]睾丸激素和[(14)C]雄烯二酮的代谢-MB 231细胞,处于不同的底物浓度(1-10μM)和时间段(30分钟-48小时)。培养的非雌激素依赖性HeLa和酵母细胞用作对照。通过反向同位素稀释对代谢物进行鉴定和定量。在MCF-7细胞中发现了一种独特的雄激素代谢模式,即5alpha-androstane-3alpha,17beta-diol(3alpha,5alpha-diol)及其3beta epimer(3beta,5alpha-diol),这是睾丸激素的主要转化产物。 (48.3%),其中以5alpha-dihydrotestosterone为中介。 3α,5α-二醇和3β,5α-二醇(二醇)的形成与底物浓度和时间有关,并被非那雄胺废除。相反,在MDA-MB 231,HeLa和酵母细胞培养中几乎没有观察到任何二醇的形成。额外的酶基因表达研究表明,与MDA-MB 231细胞相比,MCF-7细胞中5α-类固醇还原酶1型过度表达。在共表达人类雌激素受体(hER)基因的α或β亚型和雌激素反应性报告基因的表达载体的HeLa细胞中评估了二醇的类雌激素活性。结果表明3β,5α-二醇和较小程度的3α,5α-二醇以高相对亲和力与hERα和hERβ结合。两种二醇均以剂量响应方式诱导hER介导的报告基因反式激活,与雌二醇诱导的类似,尽管效力较低,但被ICI-182 780所废除。此外,3beta,5alpha-二醇程度较低3alpha,5alpha-diol诱导MCF-7细胞增殖。总体结果表明,MCF-7细胞显示出增强的雄激素代谢酶表达和活性,导致快速和大量的二醇形成,并提供了证据表明这些雄激素代谢物在基因组水平上在雌激素中发挥了强大的雌激素激动作用。依赖性乳腺癌细胞。数据表明,二醇可能在乳腺癌中充当原位内分泌因子,并且其形成可以在药理学上得到抑制。
  • 【连接蛋白43的过表达增强了高胰岛素血症引起的低血糖症。】 复制标题 收藏 收藏
    DOI:10.1210/endo.138.7.5261 复制DOI
    作者列表:Vozzi C,Bosco D,Dupont E,Charollais A,Meda P
    BACKGROUND & AIMS: To assess whether cell to cell communications via connexins (Cx) participate to insulin secretion in vivo, we studied insulinoma cells (INS1) implanted in rats after stable transfection with connexin 43 (Cx43). We found that compared to wild-type and transfected cells, which in vivo express modest levels of Cx43 and junctional communication, cells overexpressing Cx43 communicated extensively, featured decreased growth, and induced a much higher hyperinsulinemia. As a result, rats with insulinomas made of these cells became more severely hypoglycemic than rats implanted with either wild-type, neomycin-transfected cells or cells transfected with a Cx43 antisense complementary DNA. Rats implanted with transfected cells that expressed modest level of Cx43 showed levels of circulating insulin similar to those in rats implanted with wild-type INS1 cells. The data show that overexpression of Cx43 influences the growth and secretion of the implanted insulinoma cells, providing evidence for a contribution of Cx-mediated cell to cell communication in the functioning of insulin-producing cells in vivo.

    背景与目标: 为了评估通过连接蛋白(Cx)进行的细胞间通信是否参与体内胰岛素分泌,我们研究了用连接蛋白43(Cx43)稳定转染后在大鼠体内植入的胰岛素瘤细胞(INS1)。我们发现,与野生型和转染细胞相比,在体内表达适度水平的Cx43和交界处的通讯,过表达Cx43的细胞广泛地通讯,其特征是生长减少,并诱导更高的高胰岛素血症。结果,与植入野生型新霉素转染的细胞或转染了Cx43反义互补DNA的细胞的大鼠相比,由这些细胞制成的胰岛素瘤大鼠的降血糖作用更为严重。植入表达Cx43水平适度的转染细胞的大鼠,其循环胰岛素水平与植入野生型INS1细胞的大鼠相似。数据表明,Cx43的过表达影响植入的胰岛素瘤细胞的生长和分泌,为Cx介导的细胞在体内胰岛素产生细胞的功能中对细胞通讯的贡献提供了证据。

  • 【胆固醇和低温增强了囊泡与平面膜的融合。】 复制标题 收藏 收藏
    DOI:10.1016/j.chemphyslip.2012.11.004 复制DOI
    作者列表:Lee DE,Lew MG,Woodbury DJ
    BACKGROUND & AIMS: :Lipid composition and properties play an important role in many cellular properties such as fusion of vesicles to cell membranes, an essential process for exocytosis. Using a model system composed of artificial vesicles (liposomes) and artificial membranes (planar lipid bilayers), we observed that fusion is significantly affected by the lipid phase of the planar membrane. To determine the effect of lipid phases on fusion rates, we utilized the nystatin/ergosterol fusion assay and stimulated fusion with an osmotic gradient. Phase of the planar membrane was altered by changing cholesterol or temperature while the vesicular lipids were held constant. Liquid disordered (L(d) or L(α)) planar membranes were formed from phosphatidylethanolamine and phosphatidylcholine with unsaturated acyl chains. Addition of cholesterol shifts these membranes to the liquid ordered (L(o)) phase and increases liposome fusion. Planar membranes in the L(α) phase were also made from dipalmitoylphoshatidylcholine (DPPC) above the transition temperature (T(m)) of 41.5 ° C. Decreasing the temperature below T(m) shifts these membranes into the ripple phase (P(β')) and also increases liposome fusion. The cholesterol and temperature data are consistent with the hypothesis that fusion is promoted in membranes that have greater exposure of their lipid tails or in membranes which can form leaflet domains with negative curvature. The data are not consistent with the hypothesis that lipid mismatch drives fusion.
    背景与目标: 脂质的组成和性质在许多细胞性质中起着重要作用,例如囊泡与细胞膜的融合是胞吐作用的重要过程。使用由人工囊泡(脂质体)和人工膜(平面脂质双层)组成的模型系统,我们观察到融合受到平面膜脂质相的显着影响。为了确定脂质相对融合速率的影响,我们利用制霉菌素/麦角固醇融合测定法并通过渗透梯度刺激融合。通过改变胆固醇或温度来改变平面膜的相,而囊泡脂质保持恒定。液体无序(L(d)或L(α))平面膜由具有不饱和酰基链的磷脂酰乙醇胺和磷脂酰胆碱形成。胆固醇的添加将这些膜转移到液体有序(L(o))相,并增加脂质体融合。 L(α)相中的平面膜也是由高于过渡温度(T(m))41.5°C的二棕榈酰磷脂酰胆碱(DPPC)制成的。降低温度至T(m)以下会使这些膜转变为波纹相(P( β')),还可以增加脂质体融合。胆固醇和温度数据与以下假设相一致:在脂类尾巴暴露量更大的膜中或在可形成具有负曲率的小叶区域的膜中促进融合。数据与脂质错配驱动融合的假设不一致。
  • 【老年患者腹腔镜大肠切除术后增强的恢复程序。】 复制标题 收藏 收藏
    DOI:10.1111/ans.14074 复制DOI
    作者列表:Zeng WG,Liu MJ,Zhou ZX,Wang ZJ
    BACKGROUND & AIMS: BACKGROUND:The aim of this study was to investigate the feasibility and safety of an enhanced recovery programme (ERP) in patients aged ≥75 years who undergo laparoscopic surgery for colorectal cancer. METHODS:Patients were divided into two groups according to perioperative management: the ERP group (Group A, n = 94) and the conventional perioperative care group (Group B, n = 157). The postoperative outcomes were compared between two groups. RESULTS:There were no differences in terms of age, gender, American Society of Anesthesiologists score, operative time or blood loss between two groups. Postoperative return of gastrointestinal function was significantly faster in Group A compared to Group B, including time to first flatus (2 versus 3 days, P < 0.001), first stool (3 versus 4 days, P = 0.001) and oral intake (1 versus 4 days, P < 0.001). Group A was associated with lower overall postoperative complication rate (26.6% versus 44.6%, P = 0.004) and general complication rate (14.9% versus 31.2%, P = 0.004). The median postoperative hospital stay was 6 days in Group A and 8 days in Group B (P < 0.001), respectively. CONCLUSIONS:ERP following laparoscopic colorectal resection for elderly patients is associated with faster postoperative recovery, shorter postoperative hospital stay and fewer complications compared with conventional perioperative care.
    背景与目标: 摘要背景:这项研究的目的是研究对接受腹腔镜手术治疗结直肠癌的≥75岁患者进行增强恢复计划(ERP)的可行性和安全性。
    方法:根据围手术期管理将患者分为两组:ERP组(A组,n = 94)和常规围手术期护理组(B组,n = 157)。比较两组的术后结果。
    结果:两组在年龄,性别,美国麻醉医师学会评分,手术时间或失血方面均无差异。与B组相比,A组的术后胃肠功能恢复明显更快,包括第一次肠胃胀气的时间(2天比3天,P <0.001),第一次大便时间(3天比4天,P = 0.001)和口服摄入量(1天对1天)。 4天,P <0.001)。 A组的总体术后并发症发生率较低(26.6%对44.6%,P = 0.004)和一般并发症发生率(14.9%对31.2%,P = 0.004)。 A组术后中位住院时间分别为6天和B组8天(P <0.001)。
    结论:与常规围手术期护理相比,老年患者腹腔镜大肠切除术后的ERP与术后恢复更快,术后住院时间短和并发症少相关。
  • 【皮层去同步过程中增强了由感觉刺激引起的顺序神经活动模式的形成和混响。】 复制标题 收藏 收藏
    DOI:10.1016/j.neuron.2013.06.013 复制DOI
    作者列表:Bermudez Contreras EJ,Schjetnan AG,Muhammad A,Bartho P,McNaughton BL,Kolb B,Gruber AJ,Luczak A
    BACKGROUND & AIMS: :Memory formation is hypothesized to involve the generation of event-specific neural activity patterns during learning and the subsequent spontaneous reactivation of these patterns. Here, we present evidence that these processes can also be observed in urethane-anesthetized rats and are enhanced by desynchronized brain state evoked by tail pinch, subcortical carbachol infusion, or systemic amphetamine administration. During desynchronization, we found that repeated tactile or auditory stimulation evoked unique sequential patterns of neural firing in somatosensory and auditory cortex and that these patterns then reoccurred during subsequent spontaneous activity, similar to what we have observed in awake animals. Furthermore, the formation of these patterns was blocked by an NMDA receptor antagonist, suggesting that the phenomenon depends on synaptic plasticity. These results suggest that anesthetized animals with a desynchronized brain state could serve as a convenient model for studying stimulus-induced plasticity to improve our understanding of memory formation and replay in the brain.
    背景与目标: 假设记忆形成涉及学习过程中事件特定的神经活动模式的产生以及这些模式的随后自发激活。在这里,我们提供的证据表明,这些过程也可以在氨基甲酸乙酯麻醉的大鼠中观察到,并且因捏尾,皮层下卡巴胆碱输注或全身安非他明引起的失调的大脑状态而得以增强。在去同步期间,我们发现反复的触觉或听觉刺激在体感和听觉皮层中引起了神经放电的独特顺序模式,然后这些模式在随后的自发活动中再次发生,类似于我们在清醒动物中观察到的情况。此外,NMDA受体拮抗剂阻止了这些模式的形成,表明该现象取决于突触可塑性。这些结果表明,具有失步的大脑状态的麻醉动物可以作为研究刺激诱导的可塑性的便利模型,以增进我们对大脑记忆形成和重放的理解。
  • 【超声和超声造影在囊性和囊性样肝病变鉴别诊断中的诊断性能和信心。】 复制标题 收藏 收藏
    DOI:10.2214/AJR.16.17062 复制DOI
    作者列表:Corvino A,Catalano O,Corvino F,Sandomenico F,Petrillo A
    BACKGROUND & AIMS: OBJECTIVE:The aims of this study were to assess the diagnostic performance of contrast-enhanced ultrasound (CEUS) in the characterization of atypical cystic and cysticlike focal liver lesions in comparison with conventional US and to determine whether the use of CEUS can reduce the need for further diagnostic workup. SUBJECTS AND METHODS:In a 3-year period 48 patients with 50 atypical cystic and cysticlike lesions found at conventional US underwent CEUS. Diagnostic confirmation was obtained in cytohistopathologic examinations, with other imaging modalities, and in follow-up. Overall, there were 24 cystic lesions and 26 cysticlike solid lesions, specifically 32 benign and 18 malignant lesions. The conventional US and CEUS images and cine loops were reviewed by two blinded readers independently. Sensitivity, specificity, area under the ROC curve (Az), and interobserver agreement were calculated. RESULTS:Diagnostic performance improved after review of CEUS examinations by both readers (conventional US Az = 0.781 vs 0.972; CEUS Az = 0.734 vs 0.957). Interreader agreement increased, although slightly (conventional US weighted κ = 0.894; CEUS weighted κ = 0.953). In terms of differential diagnosis, the occurrence of correctly characterized lesions increased after CEUS for both readers (reader 1, 62% to 98%; reader 2, 56% to 96%). CONCLUSION:The development of low-acoustic-power CEUS has made it possible to identify several imaging features of cystic and cysticlike focal liver lesions that, in association with history and clinical findings, may help to correctly characterize them. Our data indicate the usefulness of CEUS in the evaluation of patients with these lesions.
    背景与目标: 目的:本研究的目的是评估与常规超声检查相比,超声造影(CEUS)在表征非典型性囊性和囊性样局灶性肝病中的诊断性能,并确定使用CEUS是否可以减少对超声造影的需求。进一步的诊断工作。
    研究对象和方法:在3年的时间里,对48例常规美国超声检查中发现的50例非典型囊性和囊样病变患者进行了CEUS。在细胞组织病理学检查,其他影像学检查和随访中获得了诊断确认。总体上,有24个囊性病变和26个囊样实性病变,特别是32个良性病变和18个恶性病变。两个盲人分别对常规的US和CEUS图像以及电影放映机进行了审查。计算灵敏度,特异性,ROC曲线下面积(Az)和观察者之间的一致性。
    结果:两位读者对CEUS进行检查后,诊断性能均得到改善(常规US Az = 0.781 vs 0.972; CEUS Az = 0.734 vs 0.957)。阅读器之间的一致性有所提高,尽管有所提高(常规美国加权κ= 0.894; CEUS加权κ= 0.953)。在鉴别诊断方面,两种阅读器在CEUS后正确表征病变的发生率均增加(阅读器1、62%至98%;阅读器2、56%至96%)。
    结论:低声功率CEUS的发展使得鉴别囊性和囊样性局灶性肝病的几种影像学特征与历史和临床发现相关联,可能有助于正确地表征它们。我们的数据表明CEUS在评估这些病变患者中的有用性。
  • 【电子金属-载体相互作用增强了碳化硼负载铂的氧还原活性和稳定性。】 复制标题 收藏 收藏
    DOI:10.1038/ncomms15802 复制DOI
    作者列表:Jackson C,Smith GT,Inwood DW,Leach AS,Whalley PS,Callisti M,Polcar T,Russell AE,Levecque P,Kramer D
    BACKGROUND & AIMS: :Catalysing the reduction of oxygen in acidic media is a standing challenge. Although activity of platinum, the most active metal, can be substantially improved by alloying, alloy stability remains a concern. Here we report that platinum nanoparticles supported on graphite-rich boron carbide show a 50-100% increase in activity in acidic media and improved cycle stability compared to commercial carbon supported platinum nanoparticles. Transmission electron microscopy and x-ray absorption fine structure analysis confirm similar platinum nanoparticle shapes, sizes, lattice parameters, and cluster packing on both supports, while x-ray photoelectron and absorption spectroscopy demonstrate a change in electronic structure. This shows that purely electronic metal-support interactions can significantly improve oxygen reduction activity without inducing shape, alloying or strain effects and without compromising stability. Optimizing the electronic interaction between the catalyst and support is, therefore, a promising approach for advanced electrocatalysts where optimizing the catalytic nanoparticles themselves is constrained by other concerns.
    背景与目标: :在酸性介质中催化氧的还原是一项长期挑战。尽管可以通过合金化显着提高最活泼的金属铂的活性,但合金的稳定性仍然值得关注。在这里,我们报告说,与商业碳载铂纳米颗粒相比,负载在富含石墨的碳化硼上的铂纳米颗粒在酸性介质中的活性提高了50-100%,并且循环稳定性得到了改善。透射电子显微镜和X射线吸收精细结构分析证实了两种载体上相似的铂纳米颗粒形状,大小,晶格参数和簇堆积,而X射线光电子和吸收光谱表明电子结构发生了变化。这表明纯电子金属-载体相互作用可以显着改善氧还原活性,而不会引起形状,合金或应变效应,并且不会损害稳定性。因此,优化催化剂和载体之间的电子相互作用是用于高级电催化剂的有前途的方法,其中优化催化纳米颗粒本身受到其他问题的限制。
  • 【AFEX™预处理玉米秸秆的连续SSCF使用商业酶和酿酒酵母424A(LNH-ST)可以提高乙醇生产率。】 复制标题 收藏 收藏
    DOI:10.1002/bit.24797 复制DOI
    作者列表:Jin M,Gunawan C,Balan V,Yu X,Dale BE
    BACKGROUND & AIMS: :High productivity processes are critical for commercial production of cellulosic ethanol. One high productivity process-continuous hydrolysis and fermentation-has been applied in corn ethanol industry. However, little research related to this process has been conducted on cellulosic ethanol production. Here, we report and compare the kinetics of both batch SHF (separate hydrolysis and co-fermentation) and SSCF (simultaneous saccharification and co-fermentation) of AFEX™ (Ammonia Fiber Expansion) pretreated corn stover (AFEX™-CS). Subsequently, we designed a SSCF process to evaluate continuous hydrolysis and fermentation performance on AFEX™-CS in a series of continuous stirred tank reactors (CSTRs). Based on similar sugar to ethanol conversions (around 80% glucose-to-ethanol conversion and 47% xylose-to-ethanol conversion), the overall process ethanol productivity for continuous SSCF was 2.3- and 1.8-fold higher than batch SHF and SSCF, respectively. Slow xylose fermentation and high concentrations of xylose oligomers were the major factors limiting further enhancement of productivity.
    背景与目标: :高生产率工艺对于纤维素乙醇的商业化生产至关重要。一种高生产率的过程-连续水解和发酵-已应用于玉米乙醇工业。但是,有关纤维素乙醇生产的研究很少与此过程有关。在这里,我们报告并比较了AFEX™(氨纤维膨胀)预处理玉米秸秆(AFEX™-CS)的批次SHF(单独的水解和共同发酵)和SSCF(同时糖化和共同发酵)的动力学。随后,我们设计了一种SSCF工艺,以评估一系列连续搅拌釜反应器(CSTR)在AFEX™-CS上的连续水解和发酵性能。基于相似的糖到乙醇转化率(大约80%的葡萄糖到乙醇转化率和47%的木糖到乙醇转化率),连续SSCF的总工艺乙醇生产率比批次SHF和SSCF高2.3到1.8倍,分别。木糖发酵缓慢和木糖低聚物浓度高是限制生产率进一步提高的主要因素。
  • 【the门手术后儿童次最大运动的增强生理功能。】 复制标题 收藏 收藏
    DOI:10.1249/MSS.0b013e31827b0b20 复制DOI
    作者列表:Banks L,McCrindle BW,Russell JL,Longmuir PE
    BACKGROUND & AIMS: PURPOSE:After the Fontan procedure, children exhibit reduced peak exercise capacity, yet their submaximal exercise response remains unclear. This study sought to determine the relationship between submaximal and peak exercise capacity and physical activity in Fontan patients. METHODS:This cross-sectional study recruited 50 Fontan patients (59% males) with a median age of 9 yr (range = 6-12 yr). The median age at Fontan procedure was 2.9 yr (range = 1.6-9.1 yr). Study assessments included medical history, exercise testing, and accelerometry. RESULTS:Significantly lower submaximal oxygen consumption (V˙O2) and HR in response to a standardized workload than published values for healthy children (mean ± SD) of -1.72 ± 5.24 (P < 0.001) and -1.45 ± 1.98 (P < 0.001), respectively, suggest enhanced submaximal work efficiency in this group of patients after Fontan. Higher submaximal V˙O2 z-score was associated with higher submaximal HR z-score (P = 0.02) and lower body mass index z-score (P = 0.01). Higher V˙O2peak was associated with higher submaximal V˙O2 z-score (P < 0.01), male sex (P = 0.03), higher RER (P = 0.02), lower submaximal HR z-score (P < 0.01), and higher chronotropic responsiveness (P < 0.0001). Exercise test duration z-score was associated with lower submaximal HR z-score (P = 0.02) and higher chronotropic responsiveness (P = 0.02). CONCLUSIONS:Fontan patients exhibited a lower submaximal V˙O2 and HR responsiveness at a given workload than healthy controls did during standardized exercise testing. Thus, they may be better adapted to perform submaximal exercise. Although peak exercise capacity is limited, Fontan patients are able to perform submaximal physical activities at the same level as their healthy peers.
    背景与目标: 目的:进行丰坦手术后,儿童的峰值运动能力下降,但其次最大运动反应仍不清楚。这项研究试图确定丰坦患者亚最大和最大运动能力与身体活动之间的关系。
    方法:这项横断面研究招募了50名Fontan患者(男性占59%),中位年龄为9岁(范围= 6-12岁)。丰坦手术的中位年龄为2.9岁(范围= 1.6-9.1岁)。研究评估包括病史,运动测试和加速度计。
    结果:标准化工作量下的最大摄氧量(V˙O2)和HR显着低于健康儿童的公布值(平均值±SD)的-1.72±5.24(P <0.001)和-1.45±1.98(P <0.001) )分别表明,在接受Fontan治疗后,该组患者的工作效率得到了提高。较高的V subO2 z评分较高与较高的HR z评分较低(P = 0.02)和较低的体重指数z评分(P = 0.01)相关。较高的V˙O2peak与较高的V˙O2z分数(P <0.01),男性(P = 0.03),较高的RER(P = 0.02),较低的最大HR z分数(P <0.01)和较高的Z分数相关。更高的变时响应性(P <0.0001)。运动测试持续时间z分数与较低的最大心率z分数(P = 0.02)和较高的变时反应性(P = 0.02)相关。
    结论:在标准的运动测试中,与健康对照组相比,在一定的工作量下,Fontan患者表现出低于最大的V˙O2和HR反应性。因此,它们可能更好地适于进行次最大运动。尽管峰值运动能力有限,但Fontan患者能够以与健康同龄人相同的水平进行次最大的体育锻炼。
  • 【锰增强的磁共振成像描绘了急性和慢性疼痛模型中的大脑活动:研究实验性自发性疼痛的新窗口?】 复制标题 收藏 收藏
    DOI:10.1016/j.neuroimage.2017.06.034 复制DOI
    作者列表:Devonshire IM,Burston JJ,Xu L,Lillywhite A,Prior MJ,Watson DJG,Greenspon CM,Iwabuchi SJ,Auer DP,Chapman V
    BACKGROUND & AIMS: :Application of functional imaging techniques to animal models is vital to understand pain mechanisms, but is often confounded by the need to limit movement artefacts with anaesthesia, and a focus on evoked responses rather than clinically relevant spontaneous pain and related hyperalgesia. The aim of the present study was to investigate the potential of manganese-enhanced magnetic resonance imaging (MEMRI) to measure neural responses during on-going pain that underpins hyperalgesia in pre-clinical models of nociception. As a proof of concept that MEMRI is sensitive to the neural activity of spontaneous, intermittent behaviour, we studied a separate positive control group undergoing a voluntary running wheel experiment. In the pain models, pain behaviour (weight bearing asymmetry and hindpaw withdrawal thresholds (PWTs)) was measured at baseline and following either intra-articular injection of nerve growth factor (NGF, 10µg/50µl; acute pain model, n=4 rats per group), or the chondrocyte toxin monosodium iodoacetate (MIA, 1mg/50µl; chronic model, n=8 rats per group), or control injection. Separate groups of rats underwent a voluntary wheel running protocol (n=8 rats per group). Rats were administered with paramagnetic ion Mn2+ as soluble MnCl2 over seven days (subcutaneous osmotic pump) to allow cumulative activity-dependent neural accumulation in the models of pain, or over a period of running. T1-weighted MR imaging at 7T was performed under isoflurane anaesthesia using a receive-only rat head coil in combination with a 72mm volume coil for excitation. The pain models resulted in weight bearing asymmetry (NGF: 20.0 ± 5.2%, MIA: 15 ± 3%), and a reduction in PWT in the MIA model (8.3 ± 1.5g) on the final day of assessment before undergoing MR imaging. Voxel-wise and region-based analysis of MEMRI data did not identify group differences in T1 signal. However, MnCl2 accumulation in the VTA, right Ce amygdala, and left cingulate was negatively correlated with pain responses (greater differences in weight bearing), similarly MnCl2 accumulation was reduced in the VTA in line with hyperalgesia (lower PWTs), which suggests reduced regional activation as a result of the intensity and duration of pain experienced during the 7 days of MnCl2 exposure. Motor cortex T1-weighted signal increase was associated with the distance ran in the wheel running study, while no between group difference was seen. Our data suggest that on-going pain related signal changes identified using MEMRI offers a new window to study the neural underpinnings of spontaneous pain in rats.
    背景与目标: :功能成像技术在动物模型中的应用对于理解疼痛机制至关重要,但通常因需要限制运动伪影并进行麻醉,并且侧重于诱发反应而不是临床相关的自发性疼痛和相关的痛觉过敏而感到困惑。本研究的目的是研究锰增强磁共振成像(MEMRI)在持续疼痛过程中测量神经痛的潜力,该疼痛是临床前伤害觉模型中痛觉过敏的基础。作为MEMRI对自发性,间歇性行为的神经活动敏感的概念的证明,我们研究了一个单独的阳性对照组,他们接受了一项自愿的自转轮实验。在疼痛模型中,在基线时以及关节内注射神经生长因子(NGF,10µg / 50µl;急性疼痛模型,每只n = 4只大鼠)后,测量基线时的疼痛行为(负重不对称和后爪缩回阈值(PWT))。组)或软骨细胞毒素碘乙酸单钠(MIA,1mg / 50µl;慢性模型,每组n = 8只大鼠)或对照注射液。单独的大鼠组接受自愿轮转方案(每组n = 8只大鼠)。在7天(皮下渗透泵)中,给大鼠施用了顺磁性离子Mn2作为可溶的MnCl2,以允许在疼痛模型中或在一段时间内累积依赖于活动的神经蓄积。在异氟烷麻醉下,使用仅接收的大鼠头部线圈和72mm体积线圈进行激励,在异氟烷麻醉下进行7T的T1加权MR成像。疼痛模型导致负重不对称(NGF:20.0±5.2%,MIA:15±3%),并且在进行MR成像前的评估的最后一天,MIA模型中的PWT减少(8.3±1.5g)。 MEMRI数据的基于体素分析和基于区域的分析未发现T1信号中的组差异。但是,VTA,右侧杏仁核和左扣带中的MnCl2积累与疼痛反应呈负相关(负重差异更大),与痛觉过敏一致,VTA中的MnCl2积累减少(PWT较低),这表明区域性减少MnCl2暴露7天期间疼痛的强度和持续时间的结果是激活。运动皮层T1加权信号的增加与车轮行驶研究中的跑步距离相关,而两组之间未见差异。我们的数据表明,使用MEMRI识别的与疼痛相关的持续信号变化为研究大鼠自发性疼痛的神经基础提供了新的窗口。
  • 【冠状动脉侧支动脉发育不足的患者会增强β干扰素的信号传导,并抑制小鼠的动脉生成。】 复制标题 收藏 收藏
    DOI:10.1161/CIRCRESAHA.108.171827 复制DOI
    作者列表:Schirmer SH,Fledderus JO,Bot PT,Moerland PD,Hoefer IE,Baan J Jr,Henriques JP,van der Schaaf RJ,Vis MM,Horrevoets AJ,Piek JJ,van Royen N
    BACKGROUND & AIMS: :Stimulation of collateral artery growth in patients has been hitherto unsuccessful, despite promising experimental approaches. Circulating monocytes are involved in the growth of collateral arteries, a process also referred to as arteriogenesis. Patients show a large heterogeneity in their natural arteriogenic response on arterial obstruction. We hypothesized that circulating cell transcriptomes would provide mechanistic insights and new therapeutic strategies to stimulate arteriogenesis. Collateral flow index was measured in 45 patients with single-vessel coronary artery disease, separating collateral responders (collateral flow index, >0.21) and nonresponders (collateral flow index, < or 1). Isolated monocytes were stimulated with lipopolysaccharide or taken into macrophage culture for 20 hours to mimic their phenotype during arteriogenesis. Genome-wide mRNA expression analysis revealed 244 differentially expressed genes (adjusted P, <0.05) in stimulated monocytes. Interferon (IFN)-beta and several IFN-related genes showed increased mRNA levels in 3 of 4 cellular phenotypes from nonresponders. Macrophage gene expression correlated with stimulated monocytes, whereas resting monocytes and progenitor cells did not display differential gene regulation. In vitro, IFN-beta dose-dependently inhibited smooth muscle cell proliferation. In a murine hindlimb model, perfusion measured 7 days after femoral artery ligation showed attenuated arteriogenesis in IFN-beta-treated mice compared with controls (treatment versus control: 31.5+/-1.2% versus 41.9+/-1.9% perfusion restoration, P<0.01). In conclusion, patients with differing arteriogenic response as measured with collateral flow index display differential transcriptomes of stimulated monocytes. Nonresponders show increased expression of IFN-beta and its downstream targets, and IFN-beta attenuates proliferation of smooth muscle cells in vitro and hampers arteriogenesis in mice. Inhibition of IFN-beta signaling may serve as a novel approach for the stimulation of collateral artery growth.
    背景与目标: :尽管有希望的实验方法,迄今为止刺激患者的侧支动脉生长仍未成功。循环单核细胞参与侧支动脉的生长,这一过程也称为动脉生成。患者在对动脉阻塞的自然致动脉反应中表现出很大的异质性。我们假设循环的细胞转录组将提供机制的见解和刺激动脉生成的新治疗策略。在45例单支冠状动脉疾病患者中测量了侧支血流指数,将侧支反应者(侧支血流指数,> 0.21)和无反应者(侧支血流指数,<或1)分开。用脂多糖刺激分离的单核细胞或将其置于巨噬细胞培养物中20小时以模拟其在动脉生成过程中的表型。全基因组mRNA表达分析显示受刺激的单核细胞中244个差异表达的基因(校正后的P,<0.05)。干扰素(IFN)-β和一些与IFN相关的基因在来自无应答者的4种细胞表型中有3种显示出增加的mRNA水平。巨噬细胞基因表达与刺激的单核细胞相关,而静止的单核细胞和祖细胞没有显示差异的基因调控。在体外,IFN-β剂量依赖性抑制平滑肌细胞增殖。在鼠后肢模型中,股动脉结扎后7天测量的灌注显示,与对照组相比,经IFN-β治疗的小鼠的动脉生成减弱(治疗组与对照组:31.5 /-1.2%对41.9 /-1.9%灌注恢复,P <0.01) 。总之,用侧支血流指数测量的具有不同动脉生成反应的患者表现出受刺激的单核细胞转录组差异。无反应者显示IFN-β及其下游靶标的表达增加,并且IFN-β减弱了体外平滑肌细胞的增殖并阻碍了小鼠的动脉生成。 IFN-β信号的抑制可能作为刺激侧支动脉生长的一种新方法。
  • 【对比增强心肌梗死后大鼠心脏重塑和功能的超声心动图随访。】 复制标题 收藏 收藏
    DOI:10.1016/j.ultrasmedbio.2007.04.016 复制DOI
    作者列表:Rabald S,Hagendorff A,Pfeiffer D,Zimmer HG,Deten A
    BACKGROUND & AIMS: :Echocardiography is a reliable and commonly used method to examine cardiac diseases. Recent employment of modern technologies provides new opportunities to study left ventricular (LV) remodeling after myocardial infarction (MI) also in small rodents. LV volumes as most important prognostic parameters can be estimated by noncontrast enhanced echocardiography in rats from M-mode or single cross sections only. In this study, contrast enhanced echocardiography and volume measurements by the biplane method of discs (Simpson's rule) were applied in rats to monitor remodeling and function after MI. MI was induced in female Sprague-Dawley rats (n = 26 for MI, and n = 16 for sham). LV remodeling and heart function were serially studied by contrast enhanced echocardiography for 12 to 16 wk. At the end of the observation periods hemodynamic data were additionally measured by left and right heart catheterization. LV end systolic volume (LVESV) measured by biplane method of discs correlated best with LV developed pressure as indicator for severely impaired heart function. Interestingly, LV end systolic area (LVESA) from native short axis view correlated well with LVESV (R(2) = 0.93) and was the second best predictor for depressed heart function. Moreover, left atrial size was a powerful indicator of severely impaired heart function whereas ejection fraction or fractional area change were primarily related to infarct size. In conclusion, contrast enhanced echocardiography in rats is feasible and an economical method to study time-dependent LV remodeling and deterioration of contractile function after MI.
    背景与目标: :超声心动图检查是一种可靠且常用的检查心脏疾病的方法。最近使用现代技术为小型啮齿动物心肌梗死(MI)后研究左心室(LV)重塑提供了新的机会。左室容积是最重要的预后参数,可通过M型或单个断面大鼠的非对比增强超声心动图进行评估。在这项研究中,对比增强超声心动图和双平面盘法测量体积(辛普森法则)应用于大鼠,以监测心梗后的重塑和功能。 MI在雌性Sprague-Dawley大鼠中诱发(MI = 26,假手术= 16)。左心室重塑和心脏功能通过对比增强超声心动图连续研究12至16周。在观察期结束时,通过左,右心脏导管检查另外测量血流动力学数据。通过双平面椎间盘法测量的左室收缩末期容积(LVESV)与左室发育压力最相关,后者可作为严重损害心脏功能的指标。有趣的是,从本机短轴视图来看,LV收缩末期面积(LVESA)与LVESV相关性很好(R(2)= 0.93),是心脏功能低下的第二佳预测指标。此外,左心房大小是严重损害心脏功能的有力指标,而射血分数或分数面积变化主要与梗死面积有关。总之,对比增强超声心动图在大鼠中是可行的,是一种经济的方法来研究时间依赖性左室重塑和心肌梗死后收缩功能的恶化。

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