直径小于1 cm孤立性肺结节的18F-FDG PET/CT诊断研究进展

孤立性肺结节的鉴别诊断一直是胸部影像学的研究热点。早期且准确地鉴别肺内小结节的良恶性,对于患者治疗方案的确定以及随访情况的评估均具有重要的临床意义。~(18)F-FDG PET/CT在鉴别诊断恶性肿瘤方面具有明显优于其他传统检查的高特异性和高敏感性,其公认的恶性肿瘤的诊断阈值是最大化标准摄取值(maximum standard uptake value, SUVmax)为2.5,然而部分临床数据显示一些直径小于1 cm的恶性肺结节的SUVmax数值小于2.5。因此在早期研究中,~(18)F-FDG PET/CT在诊断直径较小的肺结节的其临床价值仍存在争议。为了尽量降低SUVmax的测量误差,提高~(18)F-FDG PET/CT诊断的准确率,衍生出了许多SUVmax辅助诊断方法以及优化的重建算法、放射性显像剂的联合应用等手段。本文将对~(18)F-FDG PET/CT鉴别诊断直径小于1 cm孤立性肺结节的研究进展进行综述。     

Therapeutic strategies targeting somatic stem cells: Chemical approaches

Therapeutic modulation of fate and behavior of somatic stem cells can generate safe and functional cells ex vivo for cell-based therapy, or to repair and regenerate damaged tissues in vivo. Chemical approaches involving small molecules have provided promising approaches for modulating cellular fate and function. These strategies offer opportunities that support regenerative medicine. Here, we discuss strategies targeting somatic stem cells through chemical approaches, highlighting their progression as well as future prospects.     

A small molecule inhibitor of PCSK9 that antagonizes LDL receptor binding via interaction with a cryptic PCSK9 binding groove

Proprotein convertase (PC) subtilisin kexin type 9 (PCSK9) inhibits the clearance of low density lipoprotein (LDL) cholesterol from plasma by directly interacting with the LDL receptor (LDLR). As the interaction promotes elevated plasma LDL cholesterol levels and a predisposition to cardiovascular disease (CVD), it has attracted much interest as a therapeutic target. While anti-PCSK9 monoclonal antibodies have been successful in the treatment of hypercholesteremia by decreasing CVD risk, their high cost and a requirement for injection have prohibited widespread use. The advent of an orally bioavailable small molecule inhibitor of the PCSK9-LDLR interaction is an attractive alternative, however efforts have been tempered as the binding interface is unfavourable for binding by small organic molecules. Despite its challenging nature, we report herein the discovery of compound 3f as a small molecule inhibitor of PCSK9. The kinase inhibitor nilotinib emerged from a computational screen that was applied to identify compounds that may bind to a cryptic groove within PCSK9 and proximal to the LDLR-binding interface. A subsequent in vitro PCSK9-LDLR binding assay established that nilotinib was a bona fide but modest inhibitor of the interaction (IC₅₀ = 9.8 µM). Through multiple rounds of medicinal chemistry, 3f emerged as a lead-like molecule by demonstrating disruption of the PCSK9-LDLR interaction at nanomolar levels in vitro (IC₅₀ = 537 nM) with no inhibitory activity (IC₅₀ > 10 µM) against a small panel of kinases. Compound 3f restored LDL uptake by liver cells at sub-micromolar levels and demonstrated excellent bioavailability when delivered subcutaneously in mice. Most significantly, compound 3f lowered total cholesterol levels in the plasma of wild-type mice, thereby providing proof-of-concept that the notion of a small molecule inhibitor against PCSK9 is therapeutically viable.     

安徽省宣城麻村旧石器遗址调查及发掘简报

水阳江流域是长江下游右岸的一条重要支流,以上世纪80-90年代发现“水阳江旧石器地点群”为学术界所关注。2004年,安徽省文物考古研究所主持对流域内宣城麻村旧石器遗址进行考古调查与发掘工作,其中调查采集石制品71件,发掘出土石制品78件。遗址埋藏于水阳江右岸第二级河流阶地的红色黏土层中;石制品原料取自河流阶地下部的河卵石且以石英岩占绝对优势。石制品制作以锤击法为主,砸击法少量;石制品类型包括打击类、剥片类、废片类和小型工具等。石核剥片程度较低,石片多为初级剥片产品,总体显示中国南方砾石工业的特点。虽然技术组合处于模式I范畴内,但部分长度超过10 cm的石片和手镐及石刀等大型切割工具的发现,表明早期人类具备生产模式II产品的能力。根据石制品埋藏于网纹红土及上部均质红土的特点以及同长江中下游相关地区的地貌和年代对比,推测麻村遗址时代为大致为中更新世晚期至晚更新世早期。     

UM171和SR1对不同来源造血干/祖细胞体外扩增的作用研究

目的探讨小分子化合物UM171和SR1对脐带血、供者动员外周血和淋巴瘤患者自体动员外周血3种来源的造血干/祖细胞(HSPCs)体外扩增的作用。方法将3种来源的CD34+细胞分别予以UM171、SR1干预后进行体外扩增培养,记为对照组、UM171组、SR1组和UM171+SR1组。通过细胞计数检测各组总有核细胞的数量,流式细胞术检测HSPCs的比例、各谱系分化细胞的比例和HSPCs上归巢相关因子CXCR4的表达水平。多组数据若满足方差齐性,采用单因素方差分析,组间两两比较采用LSD-t检验;若方差不齐,多组间比较以及两两比较均采用Kruskal-Wallis检验。结果与对照组比较,UM171和SR1均能促进3种来源HSPCs的比例升高,同时UM171能够增加3种来源HSPCs的扩增倍数。与对照组比较,UM171处理后脐带血来源的CD33^+(髓系)细胞的比例升高,CD41^+(巨核)细胞的比例降低;SR1处理后3种来源的CD3-CD56^+(自然杀伤)细胞的比例均升高。体外扩增48 h后各组HSPCs上CXCR4的表达较培养前增加。结论UM171能够有效扩增3种来源HSPCs的数量,促进脐带血来源HSPCs分化为髓系细胞并抑制其分化为巨核细胞。SR1能够促进3种来源HSPCs分化为自然杀伤细胞。体外扩增培养可以提高3种来源HSPCs上CXCR4的表达水平。     

Le Paléolithique supérieur dans l’ouest de l’île principale du Japon

The Kinki, Chugoku and Shikoku regions are located in the western part of the Japanese mainland. This area lacks the Pleistocene volcanic soil except a part of Chugoku Mountains. For this reason, the chronology of the late Paleolithic stone industries has been mainly studied by technology and typology of the fields excavated. However, after the late 1980s, the analysis of volcanic ash that contained the Paleolithic sediments had remarkable development. As a result, the cultural layer between the distant Paleolithic sites is compared by several widespread volcanic ashes such as Aira-Tanzawa (in short AT) as key bed. In this paper, we offered chronological order of the late Paleolithic culture in these regions by comparing cultural layers on the basis of the widespread volcanic ashes, referring to typological analysis of industries. The Sétoüchi technique and Ku industry characterize the late Paleolithic culture in these regions. The Sétoüchi technique is the unique one to produce the Ku type backed knife blunting on only one side, using the particular side-blow flaking technology based on physical characteristics of sanukite stone which is a kind of andesite. However, a hypothesis named the “Sétoüchi concept” was proposed in 2001, and it has been used as a substitute of the “Sétoüchi technique” by a few Japanese researchers. So we point out the mistake of the Sétoüchi concept relying on the fact which yielded stratigraphically two different industries in the Suncheon site.     

Field output factors for small fields: A large multicentre study

PurposeThe determination of output factors in small field dosimetry is a crucial point, especially when implementing stereotactic radiotherapy (SRT). Herein, a working group of the French medical physicist society (SFPM) was created to collect small field output factors. The objective was to gather and disseminate information on small field output factors based on different detectors for various clinical SRT equipment and measurement configurations.MethodParticipants were surveyed for information about their SRT equipment, including the type of linear particle accelerator (linac), collimator settings, measurement conditions for the output factors and the detectors used. Participants had to report both the ratio of detector readings and the correction factors applied as described in the IAEA TRS-483 code of practice for nominal field sizes smaller or equal to 3 cm. Mean field output factors and their associated standard deviations were calculated when data from at least 3 linacs were available.Results23 centres were enrolled in the project. Standard deviations of the mean field output factors were systematically smaller than 1.5% for field sizes larger or equal to 1 cm and reached 5% for the smallest field size (0.5 cm). Deviations with published data were smaller than 2% except for the 0.5 cm circular fixed aperture collimator of the CyberKnife where it reached 3.5%.ConclusionThese field output factor values obtained via a large multicentre study can be considered as an external cross verification for any radiotherapy centre starting a SRT program and should help minimize systematic errors when determining small field output factors.     

Characteristics of Lipids Imbalance in Patients with Tick‐Borne Encephalitis

Using a novel approach, we have analyzed 30 parameters characterizing detailed spectrum and fractional content of LPs in plasma of patients with tick‐borne encephalitis (TBE). The blood plasma of all TBE patients (30 patients), as compared with that of healthy individuals (120 patients), is characterized by decreased concentrations of many LP subfractions and of the total concentration of all plasma LPs (hypolipoproteinemia). The observed difference in some parameters was statistically significant. Using computer‐assisted factor analysis, we have shown that according to these 30 parameters TBE patients are similar to patients with multiple sclerosis and systemic lupus erythematosus. The results provide grounds for using data on blood plasma LPs as additional criteria for diagnosis of TBE.     

乌司他丁对肠缺血-再灌注大鼠血清TNF—α，IL-6的影响

目的：通过检测血清TNF-α,IL-6的变化,评价乌司他丁对小肠缺血再灌注损伤的保护作用及机制。方法i健康Wistar大鼠84只,通过夹闭肠系膜上动脉（SMA）60min制作肠缺血模型,随机分成假手术组（C）,肠缺血再灌注组（I）,UTI治疗组（u）。根据缺血后再灌注时间不同又将I组和U组分成0min、2h和6h组。I组、U组于手术前经尾静脉分别注入生理盐水2mL、乌司他丁5×10^4U／kg,假手术组仅分离SMA,不夹闭血管。于各时点取腹主动脉血测定血清TNF-α、IL-6含量。结果：肠缺血再灌注各时相点均引起血清TNF-α、IL-6的变化,与假手术组相比,各时点TNF-α值显著升高（P〈0．01）,IL-6显著升高（P〈0．01）。u组0min、2h血清TNF-α值低于相应时点的I组（P〈0．01）;U组0min、2h、6h血清IL-6值低于相应时点的I组（P〈0．05）。结论：乌司他丁可减轻小肠缺血再灌注后的炎症反应。     

Imprinting in Plants and Its Underlying Mechanisms

Genomic imprinting (or imprinting) refers to an epigenetic phenomenon by which the allelic expression of a gene depends on the parent of origin. It has evolved independently in placental mammals and flowering plants. In plants, imprinting is mainly found in endosperm. Recent genome-wide surveys in Arabidopsis, rice, and maize identified hundreds of imprinted genes in endosperm. Since these genes are of diverse functions, endosperm development is regulated at different regulatory levels. The imprinted expression of only a few genes is conserved between Arabidopsis and monocots, suggesting that imprinting evolved quickly during speciation. In Arabidopsis, DEMETER (DME) mediates hypomethylation in the maternal genome at numerous loci (mainly transposons and repeats) in the central cell and results in many differentially methylated regions between parental genomes in the endosperm, and subsequent imprinted expression of some genes. In addition, histone modification mediated by Polycomb group (PcG) proteins is also involved in regulating imprinting. DME-induced hypomethylated alleles in the central cell are considered to produce small interfering RNAs (siRNAs) which are imported to the egg to reinforce DNA methylation. In parallel, the activity of DME in the vegetative cell of the male gametophyte demethylates many regions which overlap with the demethylated regions in the central cell. siRNAs from the demethylated regions are hypothesized to be also transferred into sperm to reinforce DNA methylation. Imprinting is partly the result of genome-wide epigenetic reprogramming in the central cell and vegetative cell and evolved under different selective pressures.