• 【如先前在大鼠中所证实的,成熟会降低小鼠中乙醇的最低肺泡麻醉剂浓度:没有物种差异。】 复制标题 收藏 收藏
    DOI:10.1097/00000539-199707000-00029 复制DOI
    作者列表:Fang Z,Ionescu P,Gong D,Kendig J,Harris A,Eger EI 2nd
    BACKGROUND & AIMS: The potency of conventional inhaled anesthetics increases with maturationthe 50% effective dose (minimum alveolar anesthetic concentration [MAC]) for conventional inhaled anesthetics in the neonatal rat or human exceeds MAC in the young adult. This increase also applies to ethanol in rats tested using MAC as the measure of anesthesia. However, the converse appears to be true for studies in mice assessed with the righting reflex; that is, adult mice are six times more resistant than neonates to the effects of ethanol. These disparate findings imply that maturation in rats and mice may produce opposing changes in the quantity or sensitivity of one or more receptors that mediate the actions of anesthetics that lead to the anesthetic state. Such a finding would be important for two reasons. First, both rodents are widely used in studies of anesthetic effects, and, thus, a species-dependent divergence in anesthetic effects has immediate experimental implications. Second, confirmation of such a species difference would supply an opportunity to test which receptors might be crucial to anesthetic mechanisms. Accordingly, we investigated whether maturation decreased ethanol potency in mice, using MAC as the measure of anesthesia. Applying standard techniques, we tested MAC for ethanol in 15 CF-1 mice aged 10 days (6-8.5 g) and in 13 mice aged 77-84 days (34-39 g). MAC decreased with maturation, and the decrease was indistinguishable from that found in our previous studies of rats.

    背景与目标: 常规吸入麻醉剂的效力随着成熟而增加,新生大鼠或人中常规吸入麻醉剂的50%有效剂量(最小肺泡麻醉剂浓度[MAC])超过了年轻成年人的MAC。这种增加也适用于使用MAC作为麻醉手段测试的大鼠中的乙醇。但是,对于用扶正反射评估的小鼠研究似乎相反。也就是说,成年小鼠对乙醇的抵抗力是新生小鼠的六倍。这些不同的发现暗示,大鼠和小鼠的成熟可能在介导导致麻醉状态的麻醉剂作用的一种或多种受体的数量或敏感性方面产生相反的变化。这样的发现很重要,原因有两个。首先,两种啮齿动物都广泛用于麻醉作用的研究,因此,麻醉作用中物种依赖性的差异具有直接的实验意义。其次,确认这种物种差异将提供一个机会来测试哪些受体可能对麻醉机制至关重要。因此,我们使用MAC作为麻醉手段,研究了成熟是否降低了小鼠的乙醇效力。应用标准技术,我们在10天(6-8.5 g)的15只CF-1小鼠和77-84天(34-39 g)的13只小鼠中测试了MAC的乙醇含量。 MAC随着成熟而降低,并且与我们先前的大鼠研究没有明显的区别。

  • 【MRI和多发性硬化症的诊断:扩大“没有更好的解释”的概念。】 复制标题 收藏 收藏
    DOI:10.1016/S1474-4422(06)70572-5 复制DOI
    作者列表:Charil A,Yousry TA,Rovaris M,Barkhof F,De Stefano N,Fazekas F,Miller DH,Montalban X,Simon JH,Polman C,Filippi M
    BACKGROUND & AIMS: :Although the diagnosis of multiple sclerosis relies on the demonstration of disease dissemination in space and time, the exclusion of other neurological disorders is also essential. The limited specificity of abnormalities disclosed by MRI may increase the likelihood of diagnosis of multiple sclerosis in patients affected by other disorders. The available criteria for diagnosis of multiple sclerosis have not taken advantage of the potential of MRI to detect features "not suggestive" of multiple sclerosis. Recognition of such features in the work-up of patients suspected of having multiple sclerosis may reduce the likelihood of a false positive diagnosis of the disorder in some, while suggesting the correct alternative diagnosis in other patients. On the basis of this, a workshop of the European MAGNIMS (Magnetic Resonance Network in Multiple Sclerosis) was held to define a series of MRI red flags in the setting of clinically suspected multiple sclerosis that is derived from evidence-based findings and educated guesses. The presence of such red flags should alert clinicians to reconsider the differential diagnosis more extensively. In this review we will report on the conclusions of this international consensus, which should represent a first step beyond the concept of "no better explanation", and inform future diagnostic criteria for multiple sclerosis.
    背景与目标: :尽管多发性硬化症的诊断依赖于疾病在时空上的传播,但排除其他神经系统疾病也是必不可少的。 MRI揭示的异常特异性有限,可能会增加受其他疾病影响的患者诊断为多发性硬化症的可能性。诊断多发性硬化症的可用标准尚未利用MRI的潜力来检测“不提示”多发性硬化症的特征。在怀疑患有多发性硬化症的患者进行检查时,认识到此类特征可能会减少某些患者对该疾病进行假阳性诊断的可能性,同时建议其他患者进行正确的替代性诊断。在此基础上,召开了欧洲MAGNIMS(多发性硬化症磁共振网络)研讨会,以定义临床可疑的多发性硬化症中的一系列MRI危险信号,这些证据来自循证研究结果和有根据的猜测。此类危险信号的出现应提醒临床医生更广泛地重新考虑鉴别诊断。在这篇综述中,我们将报告这一国际共识的结论,该结论应代表“没有更好的解释”概念之外的第一步,并为将来的多发性硬化症诊断标准提供依据。
  • 【玻璃体切除术用于近视眼中心凹切开术,内膜剥落,无气体压塞。】 复制标题 收藏 收藏
    DOI:10.1097/IAE.0b013e3182a0e477 复制DOI
    作者列表:Uchida A,Shinoda H,Koto T,Mochimaru H,Nagai N,Tsubota K,Ozawa Y
    BACKGROUND & AIMS: PURPOSE:To evaluate the outcome of vitrectomy with internal limiting membrane peeling and no gas tamponade in the treatment of eyes with myopic foveoschisis. METHODS:Medical records of 10 eyes of 9 consecutive patients with myopic foveoschisis without macular hole treated by vitrectomy were reviewed. RESULTS:The patients' refractive error was -4.00 diopters to -34.00 diopters, and axial length was 28.38 mm to 35.90 mm. Six eyes had foveal retinal detachment with retinoschisis. All cases were treated by vitrectomy with internal limiting membrane removal without gas tamponade. The mean preoperative best-corrected visual acuity was 0.61 ± 0.42 in logarithm of the minimum angle of resolution units (Snellen equivalent of 20/82). Myopic foveoschisis was reduced in 8 eyes (80%) with a single surgery. Two eyes without improvement developed a postoperative macular hole and were treated by additional vitreoretinal surgery. All 10 eyes showed anatomical repair, and 5 eyes showed improvement in best-corrected visual acuity to 0.47 ± 0.48 (Snellen equivalent of 20/60), by 17 months after the initial surgery. CONCLUSION:Vitrectomy with internal limiting membrane peeling and no gas tamponade can effectively treat some cases of myopic foveoschisis, suggesting that tractional forces at the vitreoretinal interface may contribute to the pathogenesis of myopic foveoschisis, thereby avoiding gas tamponade.
    背景与目标: 目的:评价玻璃体切除术的内部限制膜剥离和无气体填塞术治疗近视眼中心凹眼的效果。
    方法:回顾性分析了玻璃体切除术治疗连续9例无黄斑裂孔的近视眼中心凹患者10只眼的病历。
    结果:患者的屈光不正为-4.00屈光度至-34.00屈光度,轴长为28.38 mm至35.90 mm。六只眼出现视网膜中央凹并发视网膜中央凹。所有病例均通过玻璃体切除术切除了内部限制膜而未发生气塞。术前最佳矫正视力的平均值为分辨率单位最小角度的对数(Snellen等效为20/82)为0.61±0.42。一次手术可减少8眼(80%)的近视眼中心凹病。两只没有改善的眼睛在术后出现了黄斑裂孔,并接受了额外的玻璃体视网膜手术治疗。在初次手术后的17个月内,所有10眼均显示出解剖修复,并且5眼表现出最佳矫正视力改善至0.47±0.48(Snellen等效为20/60)。
    结论:玻璃体切除术具有内部限制膜剥离,无气体压塞可有效治疗某些近视眼中心凹的病例,提示玻璃体视网膜界面的牵引力可能是导致近视眼中心凹的原因,从而避免了气体填塞。
  • 【没有嵌合体作为阿尔茨海默氏病的治疗剂。】 复制标题 收藏 收藏
    DOI:10.2174/156720506777632925 复制DOI
    作者列表:Thatcher GR,Bennett BM,Reynolds JN
    BACKGROUND & AIMS: :NO is an important messenger molecule in the brain, playing an important role in learning and memory, in particular via the ERK/CREB signaling pathway. NO is also a neuroprotective agent; multiple mechanisms having been demonstrated that can contribute to cell survival as levels of antioxidants and trophic factors are reduced with aging. Small molecules that mimic the biological activity of NO, including NO donors, may thus ameliorate cognition and provide neuroprotection. Several lines of evidence have linked the neurodegeneration and dementia characteristic of Alzheimer's disease with the action of beta-amyloid protein at the alpha7-nicotinic acetylcholine receptor. The interplay of Abeta with alpha7-nicotinic ACh receptors operating via the ERK signaling cascade links the amyloid cascade and the cholinergic hypothesis in pathways that impact synaptic plasticity and memory. This interplay also provides linkages to disruption of NO/cGMP signaling in AD, and in addition, recent direct evidence has been found demonstrating that Abeta downregulates the NO/cGMP/CREB pathway. Activation of soluble guanylyl cyclase elevating cGMP in the brain represents the central element of a therapeutic approach to the treatment of AD and other neurodegenerative diseases, furthermore, evidence suggests that NO may display cGMP-independent activity and may operate via multiple biochemical signaling pathways to ensure the survival of neurons subjected to stress. GT 1061 is an NO chimera, an NO mimetic compound that contains an ancillary, synergistic pharmacophore, currently in clinical trials for Alzheimer's. NO chimeras and hybrid nitrates hold promise as therapeutics for AD with multiple sites of action.
    背景与目标: :NO是大脑中重要的信使分子,尤其是通过ERK / CREB信号通路在学习和记忆中起着重要作用。 NO也是一种神经保护剂。随着年龄的增长,抗氧化剂和营养因子的水平降低,多种机制已被证明可以促进细胞存活。模仿NO的生物活性的小分子,包括NO供体,可能会改善认知并提供神经保护作用。有几条证据将阿尔茨海默氏病的神经退行性疾病和痴呆症与β-淀粉样蛋白在α7-烟碱乙酰胆碱受体上的作用联系起来。 Abeta与通过ERK信号级联反应起作用的α7-烟碱型ACh受体之间的相互作用将淀粉样蛋白级联反应和胆碱能假说联系在一起,从而影响突触可塑性和记忆力。这种相互作用还提供了与AD中NO / cGMP信号破坏的联系,此外,最近发现的直接证据表明Abeta下调了NO / cGMP / CREB途径。大脑中可溶性鸟嘌呤环化酶升高cGMP的激活代表了治疗AD和其他神经退行性疾病的治疗方法的核心要素,此外,有证据表明NO可能显示cGMP非依赖性活性,并可能通过多种生化信号通路起作用以确保承受压力的神经元的存活。 GT 1061是一种NO嵌合体,一种NO模仿化合物,其中包含辅助的协同药效团,目前正在阿尔茨海默氏症的临床试验中。没有嵌合体和杂合硝酸盐有望作为具有多种作用位点的AD疗法。
  • 【“没有人能克服困难”:战争带来的健康挑战。】 复制标题 收藏 收藏
    DOI:10.1097/ANS.0b013e31829edcbe 复制DOI
    作者列表:Wands L
    BACKGROUND & AIMS: :Few studies have sought to explore the subjective experience of reintegration for veterans of the current Operations Enduring Freedom/Iraqi Freedom/New Dawn military campaigns, and even less attention has been given to discover strategies used by veterans to overcome difficulties with transitioning from life in a combat zone to life at home. Findings of this mixed-method study describe reintegration challenges faced by a sample of student veterans as well as some of the strategies they used in response to those challenges. This study provides direction for nurses and postsecondary educators to support veterans who struggle with their personal experience of coming home from the war.
    背景与目标: :很少有研究试图探索当前持久自由行动/伊拉克自由行动/新黎明军事行动的退伍军人重返社会的主观经验,甚至很少有人关注发现退伍军人用来克服从生活过渡到困境的策略。一个家庭生活的战斗区。这项混合方法研究的结果描述了一些学生退伍军人面临的重返社会挑战,以及他们为应对这些挑战所采用的一些策略。这项研究为护士和高等教育工作者提供指导,以支持因战争后的回家经历而苦苦挣扎的退伍军人。
  • 【清醒大鼠腹侧连合侧核中NK-1受体的阻滞对化学反射激活的心血管反应没有影响。】 复制标题 收藏 收藏
    DOI:10.1590/s0100-879x2000001100018 复制DOI
    作者列表:Zhang C,Bonagamba LG,Machado BH
    BACKGROUND & AIMS: :The neurotransmission of the chemoreflex in the nucleus tractus solitarii (NTS), particularly of the sympatho-excitatory component, is not completely understood. There is evidence that substance P may play a role in the neurotransmission of the chemoreflex in the NTS. Microinjection of substance P (50 pmol/50 nl, N = 12, and 5 nmol/50 nl, N = 8) into the commissural NTS of unanesthetized rats produced a significant increase in mean arterial pressure (101 +/- 1 vs 108 +/- 2 and 107 +/- 3 vs 115 +/- 4 mmHg, respectively) and no significant changes in heart rate (328 +/- 11 vs 347 +/- 15 and 332 +/- 7 vs 349 +/- 13 bpm, respectively) 2 min after microinjection. Previous treatment with WIN, an NK-1 receptor antagonist (2.5 nmol/50 nl), microinjected into the NTS of a specific group of rats, blocked the pressor (11 +/- 5 vs 1 +/- 2 mmHg) and tachycardic (31 +/- 6 vs 4 +/- 3 bpm) responses to substance P (50 pmol/50 nl, N = 5) observed 10 min after microinjection. Bilateral microinjection of WIN into the lateral commissural NTS (N = 8) had no significant effect on the pressor (50 +/- 4 vs 42 +/- 6 mmHg) or bradycardic (-230 +/- 16 vs -220 +/- 36 bpm) responses to chemoreflex activation with potassium cyanide (iv). These data indicate that the activation of NK-1 receptors by substance P in the NTS produces an increase in baseline mean arterial pressure and heart rate. However, the data obtained with WIN suggest that substance P and NK-1 receptors do not play a major role in the neurotransmission of the chemoreflex in the lateral commissural NTS.
    背景与目标: :孤束核(NTS)的化学反射的神经传递,特别是交感神经兴奋组分的神经传递,尚不完全清楚。有证据表明,物质P可能在NTS的化学反射的神经传递中起作用。将P物质(50 pmol / 50 nl,N = 12和5 nmol / 50 nl,N = 8)显微注射到未麻醉大鼠的连合NTS中,平均动脉压显着增加(101 /-1对108 /-显微注射后2分钟,心率分别为2和107 /-3 vs 115 /-4 mmHg),心率无明显变化(分别为328 /-11 vs 347 /-15和332 /-7 vs 349 /-13 bpm) 。先前用NK-1受体拮抗剂(2.5 nmol / 50 nl)WIN进行的先前治疗,将其微注射到特定大鼠的NTS中,阻断了升压(11 /-5 vs 1 /-2 mmHg)和心动过速(31 /在微量注射后10分钟观察到对物质P(50 pmol / 50 nl,N = 5)的反应-6 vs 4 /-3 bpm。将WIN双向显微注射到侧连合NTS(N = 8)对升压(50 /-4 vs 42 /-6 mmHg)或心动过缓(-230 /-16 vs -220 /-36 bpm)的反应无明显影响用氰化钾(iv)进行化学反射激活。这些数据表明NTS中P物质对NK-1受体的激活导致基线平均动脉压和心率增加。但是,用WIN获得的数据表明P物质和NK-1受体在侧连合NTS的化学反射神经传递中不发挥主要作用。
  • 【双侧股骨骨折不再是死亡的标志吗?】 复制标题 收藏 收藏
    DOI:10.1097/BOT.0b013e3182a83fdf 复制DOI
    作者列表:OʼToole RV,Lindbloom BJ,Hui E,Fiastro A,Boateng H,OʼBrien M,Murphy L,Copeland CE
    BACKGROUND & AIMS: OBJECTIVES:To determine whether previously reported high mortality rates associated with bilateral femoral fractures have decreased over time. DESIGN:Retrospective review. SETTING:Urban academic trauma center. PATIENTS: STUDY GROUP:54 adults with bilateral femoral fractures treated at our center from 2000 to 2006. The 108 fractures were initially treated with external fixation (11%), reamed antegrade nailing (23%), and reamed retrograde nailing (67%). Unilateral control group: 461 patients with unilateral femoral fractures treated at our center from 2002 to 2005. INTERVENTION:Univariate analysis compared our results with those of a published historical control group from the same center approximately 15 years ago (study period, 1984-1990). MAIN OUTCOME MEASUREMENTS:Mortality rates. RESULTS:We noted marked differences between the current mortality rate associated with bilateral femoral fractures and that of the historical control group. The mortality rate decreased over time at our center for both bilateral (26%-7%, P = 0.002) and unilateral (12%-2%, P = 0.0001) fractures. Mortality rates were still significantly higher (P = 0.037) for bilateral (7%) than for unilateral (2%) fractures. CONCLUSIONS:Mortality rates and Injury Severity Scores were reduced for bilateral and unilateral femoral fractures compared with data reported 15 years ago from the same center. The improved outcome might be related in part to changes in resuscitation, triage, intensive care, and orthopaedic management of the patients. However, considering that the Injury Severity Score also significantly decreased, the improvement might have occurred because of changes in injury patterns, perhaps secondary to improved safety features in motor vehicles. LEVEL OF EVIDENCE:Prognostic level III. See instructions for authors for a complete description of levels of evidence.
    背景与目标: 目的:确定先前报道的与双侧股骨骨折相关的高死亡率是否随时间降低。
    设计:回顾性审查。
    单位:城市学术创伤中心。
    耐心:
    研究小组:从2000年至2006年,我们中心对54例成年人的双侧股骨骨折进行了治疗。最初对108例骨折进行了外固定(11%),顺行扩钉(23%)和逆行扩钉(67%)。单侧对照组:2002年至2005年在我中心接受治疗的461例单侧股骨骨折患者。
    干预:单变量分析将我们的结果与大约15年前(研究期,1984-1990年)同一中心的已发表历史对照组的结果进行了比较。
    主要观察指标:死亡率。
    结果:我们注意到当前与双侧股骨骨折相关的死亡率与历史对照组之间存在显着差异。在我们中心,双侧(26%-7%,P = 0.002)和单侧(12%-2%,P = 0.0001)骨折的死亡率均随时间降低。双侧(7%)的死亡率仍显着高于单侧(2%)的骨折(P = 0.037)。
    结论:与15年前同一中心报道的数据相比,双侧和单侧股骨骨折的死亡率和严重程度评分降低。改善的结局可能部分与患者的复苏,分诊,重症监护和整形外科治疗有关。但是,考虑到伤害严重性评分也显着降低,可能是由于伤害模式的改变而导致的改善,这可能是机动车安全性得到改善之后的结果。
    证据级别:预后等级III。有关证据水平的完整说明,请参见作者说明。
  • 【Huang水提取的新型多糖通过NO的产生和IL-6和TNF-α表达的增加对THP-1细胞的免疫调节活性。】 复制标题 收藏 收藏
    DOI:10.1016/j.foodchem.2020.127257 复制DOI
    作者列表:Huo J,Wu J,Zhao M,Sun W,Sun J,Li H,Huang M
    BACKGROUND & AIMS: :Huangshui (HS), the by-product of Chinese Baijiu, has attracted considerable attention due to its nutrient and microbial composition; however, none of the studies has explored the polysaccharides in HS yet. Here, from HS, we isolated a novel polysaccharide, HSP-3, with an average molecular weight of 26.40 kDa. The structure was elucidated based on monosaccharide composition and methylation analysis, NMR, FT-IR, and AFM analysis. It is mainly composed of mannose (46.6%), galactose (17.3%), arabinose (11.2%), glucose (10.5%), xylose (8.2%), fucose (5.2%), and rhamnose (1.0%). The backbone of HSP-3 was made up of → 2)-β-d-Manp-(1 → 2,6)-β-d-Manp-(1 → 6)-β-d-Galp-(1 → 3,6)-β-d-Galp-(1 → 4)-α-l-Rhap-(1 → 3,4)-α-l-Rhap-(1 → . Moreover, stimulation of the production of ROS, NO, TNF-α and IL-6, upregulation of the mRNA and protein expression levels of TNF-α and IL-6 in THP-1 cells, and enhanced the pinocytic and phagocytic capacities of THP-1 cells exhibited significant immunomodulatory properties of HSP-3. Altogether, this study suggests that HSP-3 could be used as an active component in functional foods.
    背景与目标: :白酒的副产品hui水(HS)由于其营养成分和微生物成分而备受关注。然而,尚无研究探讨HS中的多糖。在这里,我们从HS分离出一种新型多糖HSP-3,其平均分子量为26.40 kDa。根据单糖组成和甲基化分析,NMR,FT-IR和AFM分析阐明了结构。它主要由甘露糖(46.6%),半乳糖(17.3%),阿拉伯糖(11.2%),葡萄糖(10.5%),木糖(8.2%),岩藻糖(5.2%)和鼠李糖(1.0%)组成。 HSP-3的骨架由→2)-β-d-Manp-(1→2,6)-β-d-Manp-(1→6)-β-d-Galp-(1→3组成,6)-β-d-Galp-(1→4)-α-l-Rhap-(1→3,4)-α-l-Rhap-(1→ ,TNF-α和IL-6,THP-1细胞中TNF-α和IL-6的mRNA和蛋白表达水平上调以及增强THP-1细胞的吞噬和吞噬能力表现出HSP-S的显着免疫调节特性。 3.总的来说,这项研究表明,HSP-3可以用作功能性食品中的活性成分。
  • 【NO在植物对盐胁迫的响应中的作用:与多胺的相互作用。】 复制标题 收藏 收藏
    DOI:10.1071/FP19047 复制DOI
    作者列表:Napieraj N,Reda MG,Janicka MG
    BACKGROUND & AIMS: :Soil salinity is a major abiotic stress that limits plant growth and productivity. High concentrations of sodium chloride can cause osmotic and ionic effects. This stress minimises a plant's ability to uptake water and minerals, and increases Na+ accumulation in the cytosol, thereby disturbing metabolic processes. Prolonged plant exposure to salt stress can lead to oxidative stress and increased production of reactive oxygen species (ROS). Higher plants developed some strategies to cope with salt stress. Among these, mechanisms involving nitric oxide (NO) and polyamines (PAs) are particularly important. NO is a key signalling molecule that mediates a variety of physiological functions and defence responses against abiotic stresses in plants. Under salinity conditions, NO donors increase growth parameters, reduce Na+ toxicity, maintain ionic homeostasis, stimulate osmolyte accumulation and prevent damages caused by ROS. NO enhances salt tolerance of plants via post-translational protein modifications through S-nitrosylation of thiol groups, nitration of tyrosine residues and modulation of multiple gene expression. Several reviews have reported on the role of polyamines in modulating salt stress plant response and the capacity to enhance PA synthesis upon salt stress exposure, and it is known that NO and PAs interact under salinity. In this review, we focus on the role of NO in plant response to salt stress, paying particular attention to the interaction between NO and PAs.
    背景与目标: :土壤盐分是一种主要的非生物胁迫,限制了植物的生长和生产力。高浓度的氯化钠会引起渗透和离子作用。这种胁迫使植物吸收水分和矿物质的能力降至最低,并增加了Na在细胞质中的积累,从而干扰了代谢过程。植物长时间暴露于盐胁迫下会导致氧化胁迫并增加活性氧(ROS)的产生。高等植物制定了一些应对盐胁迫的策略。其中,涉及一氧化氮(NO)和多胺(PAs)的机制尤为重要。 NO是关键信号分子,可介导植物的多种生理功能和对非生物胁迫的防御反应。在盐度条件下,NO供体会增加生长参数,降低Na毒性,保持离子稳态,刺激渗透液积累并防止ROS引起的破坏。 NO通过硫醇基团的S-亚硝基化,酪氨酸残基的硝化和多种基因表达的调节,通过翻译后蛋白质修饰增强植物的耐盐性。一些评论已经报道了多胺在调节盐胁迫植物反应中的作用以及在盐胁迫下增强PA合成的能力,并且已知NO和PA在盐度下相互作用。在这篇综述中,我们着重于NO在植物对盐胁迫的响应中的作用,特别注意NO和PA之间的相互作用。
  • 【IL-6和IL-13基因变异对中国人群肺结核易感性无明显影响。】 复制标题 收藏 收藏
    DOI:10.1089/dna.2020.5404 复制DOI
    作者列表:Sun W,Jiao L,Liu T,Song J,Wang M,Liang L,Wen C,Hu L,Qu W,Ying B
    BACKGROUND & AIMS: :Tuberculosis (TB) is an intricate infectious disease that causes a large number of deaths in the population. Interleukin (IL)-6 and IL-13 play functional roles in host resistance to Mycobacterium tuberculosis infection. Our aim in this study was to explore the association of IL-6 and IL-13 polymorphisms with TB susceptibility in the Western Chinese Han population. The case and control groups comprised 900 TB patients and 1534 healthy controls, respectively, and four single-nucleotide polymorphisms (SNPs) were genotyped in IL-6 and five SNPs in IL-13 through the improved multiplex ligation detection reaction method. We found no genetic variants in the IL-6 or IL-13 genes that were related to TB susceptibility in the analysis of alleles, genotypes, genetic models, and TB clinical subtypes, except for a trend toward low pulmonary tuberculosis and extrapulmonary tuberculosis susceptibility for the SNPs rs1295686 and rs20541. Our study did not find a link between IL-6 and IL-13 polymorphisms and TB susceptibility in the Western Chinese Han population. Therefore, our present data revealed the challenge of applying IL-6 and IL-13 SNPs as genetic markers for TB and that increased sample sizes and additional races are needed for further studies.
    背景与目标: 结核病(TB)是一种复杂的传染病,会导致人口大量死亡。白介素(IL)-6和IL-13在宿主对结核分枝杆菌感染的抗性中发挥功能性作用。我们在这项研究中的目的是探讨中国西部汉族人群中IL-6和IL-13多态性与结核病易感性的关系。病例组和对照组分别包括900 TB患者和1534名健康对照组,并通过改进的多重连接检测反应方法对IL-6中的四个单核苷酸多态性(SNP)和IL-13中的五个SNP进行了基因分型。在等位基因,基因型,遗传模型和结核病临床亚型分析中,我们没有发现与结核易感性相关的IL-6或IL-13基因的遗传变异,除了低肺结核和肺外结核易感性的趋势外。 SNP rs1295686和rs20541。我们的研究未发现中国西部汉族人群IL-6和IL-13多态性与结核病易感性之间存在联系。因此,我们目前的数据揭示了将IL-6和IL-13 SNPs用作结核病的遗传标志物所面临的挑战,并且需要进一步增加样本量和其他种族。
  • 【积液中CK5 / 6:间皮瘤与肺腺癌和非肺腺癌之间无差异。】 复制标题 收藏 收藏
    DOI:10.1159/000325601 复制DOI
    作者列表:Dejmek A
    BACKGROUND & AIMS: OBJECTIVE:To test the performance of CK5/6 for the differentiation between mesothelioma, adenocarcinoma and benign mesothelia/proliferations in effusion cytology. STUDY DESIGN:CKS/6 immunocytochemistry was applied to ethanol-fixed cytospin preparations from 74 benign and malignant effusions. RESULTS:Reactivity was seen in 7 of 8 mesotheliomas and in 9 of 11 benign mesothelial proliferations but also in 11 of l7 pulmonary adenocarcinomas and in 12 of 31 adenocarcinomas of nonpulmonary origin. Reactivity was also found in 3 of 5 non-small cell lung carcinomas and 1 of 1 squamous carcinoma. CONCLUSION:CK5/6 reactivity was found in a considerable proportion of metastatic adenocarcinomas of pulmonary and nonpulmonary origin. The high reactivity rate in pulmonary adenocarcinomas disagrees with the results obtained with histologic sections from solid tumor tissue, and CK5/6 seems to be of very limited value as an additional marker in effusion cytology.
    背景与目标: 目的:探讨CK5 / 6在间质细胞学中对间皮瘤,腺癌和良性间皮细胞/增生的分化能力。
    研究设计:CKS / 6免疫细胞化学被应用于来自74例良性和恶性积液的乙醇固定的细胞离心制备物中。
    结果:在8个间皮瘤中有7个和11个良性间皮增生中有9个反应性,但在17个肺腺癌中有11个和31个非肺源性腺癌中均可见到反应性。在5个非小细胞肺癌中有3个和1个鳞状癌中有1个也发现了反应性。
    结论:在相当一部分肺和非肺源性转移性腺癌中发现了CK5 / 6反应性。肺腺癌的高反应率与从实体瘤组织的组织学切片获得的结果不同,并且CK5 / 6作为积液细胞学中的其他标志物似乎价值非常有限。
  • 【没有证据表明在野生酵母菌系统中进行外合子后分离。】 复制标题 收藏 收藏
    DOI:10.1098/rsbl.2017.0197 复制DOI
    作者列表:Charron G,Landry CR
    BACKGROUND & AIMS: :Although microorganisms account for the largest fraction of Earth's biodiversity, we know little about how their reproductive barriers evolve. Sexual microorganisms such as Saccharomyces yeasts rapidly develop strong intrinsic post-zygotic isolation, but the role of extrinsic isolation in the early speciation process remains to be investigated. We measured the growth of F1 hybrids between two incipient species of Saccharomyces paradoxus to assess the presence of extrinsic post-zygotic isolation across 32 environments. More than 80% of hybrids showed either partial dominance of the best parent or over-dominance for growth, revealing no fitness defects in F1 hybrids. Extrinsic reproductive isolation therefore likely plays little role in limiting gene flow between incipient yeast species and is not a requirement for speciation.
    背景与目标: :尽管微生物是地球生物多样性的最大组成部分,但我们对其生殖屏障如何进化知之甚少。性微生物(例如酵母)迅速发展出强大的内在合子后分离,但是外源分离在早期物种形成过程中的作用仍有待研究。我们测量了两个Saccharomyces paradoxus初始物种之间的F1杂种的生长,以评估在32个环境中外部合子后分离的存在。超过80%的杂种显示出最佳亲本的部分优势或对生长的过度主导,表明F1杂种中没有适合性缺陷。因此,外源性生殖分离可能在限制初始酵母物种之间的基因流动方面几乎没有作用,并且不是物种形成的必要条件。
  • 【有两项研究的故事:现在不再是非整倍性植入前基因测试(PGT-A)的最佳时机。】 复制标题 收藏 收藏
    DOI:10.1007/s10815-020-01712-x 复制DOI
    作者列表:Scriven PN
    BACKGROUND & AIMS: :Preimplantation genetic testing for aneuploidy (PGT-A) does not create normal embryos, but selecting a viable embryo for a fresh transfer has the potential to deliver an extra effect for live birth from a stimulated cycle by evading the attrition associated with embryo cryopreservation. Improved genetic tests are now available for selecting viable embryos; however, current embryo cryopreservation techniques also have a superior survival rate, which means it is now possible to transfer most morphologically suitable embryos from a stimulated cycle one at a time. The cumulative live birth rate from a stimulated cycle is now unlikely to be superior compared with morphological assessment alone, with any benefit likely to be associated with a reduction in the risk of miscarriage and the time to pregnancy. This communication offers a perspective on the likely benefit and disbenefit of PGT-A based on the outcome of modern-day clinical studies. Caution should be advised regarding offering PGT-A to every woman. Quantifying the likely miscarriage benefit and live birth disbenefit for an appropriate patient group may help to better inform couples who might be considering adding aneuploidy screening to their treatment cycle.
    背景与目标: :非整倍性的胚胎植入前遗传学测试(PGT-A)不能产生正常的胚胎,但是选择一个有生命的胚胎进行新的移植有可能通过避免与胚胎冷冻保存相关的损耗而在刺激周期中为活胎带来额外的效果。现在可以使用改良的基因测试来选择有生命的胚胎。然而,目前的胚胎冷冻保存技术也具有较高的存活率,这意味着现在有可能一次从一个刺激的周期中转移出形态上最合适的胚胎。与单独的形态学评估相比,现在受刺激周期的累计活产率现在不可能更高,任何益处都可能与减少流产风险和怀孕时间有关。该交流基于现代临床研究的结果,对PGT-A可能带来的好处和不利之处提供了一个观点。在为每位女性提供PGT-A时应谨慎。对合适的患者群体量化可能的流产益处和活产不利影响,可能有助于更好地告知可能正在考虑在其治疗周期中增加非整倍性筛查的夫妇。
  • 【口服抗凝剂与抗血小板疗法可预防非瓣膜性心房颤动且无中风或短暂性脑缺血发作病史的患者。】 复制标题 收藏 收藏
    DOI:10.1002/14651858.CD006186.pub2 复制DOI
    作者列表:Aguilar MI,Hart R,Pearce LA
    BACKGROUND & AIMS: BACKGROUND:Non-valvular atrial fibrillation (AF) carries an increased risk of stroke mediated by embolism of stasis-precipitated thrombi originating in the left atrial appendage. Both oral anticoagulants and antiplatelet agents have proven effective for stroke prevention in most patients at high risk for vascular events, but primary stroke prevention in patients with non-valvular AF potentially merits separate consideration because of the suspected cardio-embolic mechanism of most strokes in AF patients. OBJECTIVES:To characterize the relative effect of long-term oral anticoagulant treatment compared with antiplatelet therapy on major vascular events in patients with non-valvular AF and no history of stroke or transient ischemic attack (TIA). SEARCH STRATEGY:We searched the Cochrane Stroke Group Trials Register (June 2006). We also searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2006), MEDLINE (1966 to June 2006) and EMBASE (1980 to June 2006). We contacted the Atrial Fibrillation Collaboration and experts working in the field to identify unpublished and ongoing trials. SELECTION CRITERIA:All unconfounded, randomized trials in which long-term (more than four weeks) adjusted-dose oral anticoagulant treatment was compared with antiplatelet therapy in patients with chronic non-valvular AF. DATA COLLECTION AND ANALYSIS:Two review authors independently selected trials for inclusion, assessed quality and extracted data. The Peto method was used for combining odds ratios after assessing for heterogeneity. MAIN RESULTS:Eight randomized trials, including 9598 patients, tested adjusted-dose warfarin versus aspirin (in dosages ranging from 75 to 325 mg/day) in AF patients without prior stroke or TIA. The mean overall follow up was 1.9 years/participant. Oral anticoagulants were associated with lower risk of all stroke (odds ratio (OR) 0.68, 95% confidence interval (CI) 0.54 to 0.85), ischemic stroke (OR 0.53, 95% CI 0.41 to 0.68) and systemic emboli (OR 0.48, 95% CI 0.25 to 0.90). All disabling or fatal strokes (OR 0.71, 95% CI 0.59 to 1.04) and myocardial infarction (OR 0.69, 95% CI 0.47 to 1.01) were substantially but not significantly reduced by oral anticoagulants. Vascular death (OR 0.93, 95% CI 0.75 to 1.15) and all cause mortality (OR 0.99, 95% CI 0.83 to 1.18), were similar with these treatments. Intracranial hemorrhages (OR 1.98, 95% CI 1.20 to 3.28) were increased by oral anticoagulant therapy. AUTHORS' CONCLUSIONS:Adjusted-dose warfarin and related oral anticoagulants reduce stroke, disabling stroke and other major vascular events for those with non-valvular AF by about one third when compared with antiplatelet therapy.
    背景与目标: 背景:非瓣膜性心房颤动(AF)会增加由左心耳产生的淤积沉淀的血栓栓塞介导的中风风险。事实证明,口服抗凝药和抗血小板药均可在大多数血管事件高风险患者中有效预防卒中,但由于怀疑大多数AF卒中的心脏栓塞机制,对非瓣膜性AF患者的初次卒中预防可能值得单独考虑耐心。
    目的:研究长期口服抗凝治疗与抗血小板治疗相比对非瓣膜性房颤,无卒中或短暂性脑缺血发作(TIA)史的患者主要血管事件的相对作用。
    搜索策略:我们搜索了Cochrane中风组试验登记册(2006年6月)。我们还搜索了Cochrane对照试验中央注册簿(CENTRAL)(2006年第2期Cochrane图书馆),MEDLINE(1966年至2006年6月)和EMBASE(1980年6月至2006年6月)。我们联系了心房颤动协作组织和该领域的专家,以确定尚未发表和正在进行的试验。
    选择标准:所有无混淆的随机试验,将长期(四周以上)调整剂量的口服抗凝治疗与抗血小板治疗相比较,用于慢性非瓣膜性房颤患者。
    数据收集与分析:两位评价作者独立选择了纳入,评估质量和提取数据的试验。评估异质性后,使用Peto方法合并比值比。
    主要结果:八项随机试验(包括9598名患者)在无中风或TIA的AF患者中测试了调整剂量的华法林与阿司匹林(剂量范围为75至325 mg / day)。平均总体随访时间为1.9年/参与者。口服抗凝剂与降低所有中风的风险(几率(OR)0.68,95%置信区间(CI)0.54至0.85),缺血性中风(OR 0.53,95%CI 0.41至0.68)和全身性栓塞(OR 0.48, 95%CI 0.25至0.90)。口服抗凝剂可以使所有致残或致命性中风(OR 0.71,95%CI 0.59至1.04)和心肌梗塞(OR 0.69,95%CI 0.47至1.01)得到显着但没有显着降低。这些治疗与血管性死亡(OR 0.93,95%CI 0.75至1.15)和所有原因死亡率(OR 0.99,95%CI 0.83至1.18)相似。口服抗凝治疗可增加颅内出血(OR 1.98,95%CI 1.20至3.28)。
    作者的结论:与抗血小板治疗相比,调整剂量的华法令和相关的口服抗凝药可使非瓣膜性房颤患者的中风,中风和其他主要血管事件减少约三分之一。
  • 【未能约束沙门氏菌的T-bet形式可诱导的NO合酶阳性肉芽肿缺乏症的小鼠。】 复制标题 收藏 收藏
    DOI:10.4049/jimmunol.2000089 复制DOI
    作者列表:
    BACKGROUND & AIMS: :Clearance of intracellular infections caused by Salmonella Typhimurium (STm) requires IFN-γ and the Th1-associated transcription factor T-bet. Nevertheless, whereas IFN-γ-/- mice succumb rapidly to STm infections, T-bet-/- mice do not. In this study, we assess the anatomy of immune responses and the relationship with bacterial localization in the spleens and livers of STm-infected IFN-γ-/- and T-bet-/- mice. In IFN-γ-/- mice, there is deficient granuloma formation and inducible NO synthase (iNOS) induction, increased dissemination of bacteria throughout the organs, and rapid death. The provision of a source of IFN-γ reverses this, coincident with subsequent granuloma formation and substantially extends survival when compared with mice deficient in all sources of IFN-γ. T-bet-/- mice induce significant levels of IFN-γ- after challenge. Moreover, T-bet-/- mice have augmented IL-17 and neutrophil numbers, and neutralizing IL-17 reduces the neutrophilia but does not affect numbers of bacteria detected. Surprisingly, T-bet-/- mice exhibit surprisingly wild-type-like immune cell organization postinfection, including extensive iNOS+ granuloma formation. In wild-type mice, most bacteria are within iNOS+ granulomas, but in T-bet-/- mice, most bacteria are outside these sites. Therefore, Th1 cells act to restrict bacteria within IFN-γ-dependent iNOS+ granulomas and prevent dissemination.
    背景与目标: :清除由鼠伤寒沙门氏菌(STm)引起的细胞内感染需要IFN-γ和Th1相关转录因子T-bet。但是,尽管IFN-γ-/-小鼠迅速死于STm感染,但T-bet-/-小鼠却没有。在这项研究中,我们评估了免疫应答的解剖结构以及与细菌感染STm感染的IFN-γ-/-和T-bet-/-小鼠的脾脏和肝脏的关系。在IFN-γ-/-小鼠中,肉芽肿形成不足和可诱导的NO合酶(iNOS)诱导,细菌在整个器官中的传播增加,并迅速死亡。与缺乏所有IFN-γ来源的小鼠相比,提供IFN-γ的来源可以逆转这种情况,与随后的肉芽肿形成同时发生,并且可以大大延长生存期。攻击后,T-bet-/-小鼠诱导显着水平的IFN-γ-。此外,T-bet-/-小鼠的IL-17和嗜中性粒细胞数目增加,而中和IL-17会减少嗜中性粒细胞,但不会影响所检测细菌的数目。出人意料的是,T-bet-/-小鼠在感染后表现出令人惊讶的野生型样免疫细胞组织,包括广泛的iNOS肉芽肿形成。在野生型小鼠中,大多数细菌都位于iNOS肉芽肿内,但在T-bet-/-小鼠中,大多数细菌都位于这些部位之外。因此,Th1细胞的作用是将细菌限制在IFN-γ依赖性iNOS肉芽肿中,并阻止其传播。

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