BACKGROUND & AIMS: Pseudomonas putida U does not degrade D-glucose through the glycolytic pathway but requires (i) its oxidation to D-gluconic acid by a peripherally located constitutive glucose dehydrogenase (insensitive to osmotic shock), (ii) accumulation of D-gluconic acid in the extracellular medium, and (iii) the induction of a specific energy-dependent transport system responsible for the uptake of D-gluconic acid. This uptake system showed maximal rates of transport at 30 degrees C in 50 mM potassium phosphate buffer, pH 7.0. Under these conditions the K(m) calculated for D-gluconic acid was 6.7 microM. Furthermore, a different transport system, specific for the uptake of glucose, was also identified. It is active and shows maximal uptake rates at 35 degrees C in 50 mM potassium phosphate buffer, pH 6.0, with a K(m) value of 8.3 microM.

背景与目标： 恶臭假单胞菌U不会通过糖酵解途径降解D-葡萄糖，但需要（i）通过位于外围的组成型葡萄糖脱氢酶（对渗透压不敏感）将其氧化为D-葡萄糖酸，（ii）D-葡萄糖酸在D葡萄糖中的积累（iii）诱导负责摄取D-葡萄糖酸的特定能量依赖性转运系统。该摄取系统显示了在30 mC，pH 7.0的50 mM磷酸钾缓冲液中的最大运输速率。在这些条件下，D-葡萄糖酸的K（m）计算值为6.7 microM。此外，还发现了一个专门针对葡萄糖吸收的不同转运系统。它是有活性的，在35 m的50 mM磷酸钾缓冲液（pH 6.0）中显示最大吸收速率，K（m）值为8.3 microM。

BACKGROUND & AIMS: CONTEXT:Concern has been raised about the safety of assisted reproduction techniques for the offspring. OBJECTIVES:The objective of the study was to investigate postnatal growth and growth factors in children born after intra-cytoplasmatic sperm injection (ICSI) and in vitro fertilization (IVF). DESIGN:The study had two cohorts: a population-based longitudinal infant cohort 0-36 months [236 ICSI, 173 IVF, 1530 naturally conceived (NC)], and a cross-sectional child cohort at 5 yr (68 ICSI, 67 IVF, 70 NC). INTERVENTION:Anthropometrical measurements were made at birth, 3, 18, 36 (infant cohort), and 60 months (child cohort), and blood samples were collected at 3 or 60 months. MAIN OUTCOME MEASURES:Serum IGF-I, IGFBP-3, height, weight, head and abdominal circumference, body mass index, and fat folds were the main outcome measures. RESULTS:Anthropometrical measurements showed no significant differences between ICSI and IVF children and controls in either cohort. However, singleton ICSI girls [3.4 (0.6) kg, P = 0.008] had a slightly lower birth weight than IVF [3.5 (0.5) kg] and NC girls [3.5 (0.5) kg]. Birth weights of singleton boys [3.6 (0.5) kg], twin boys [2.6 (0.6) kg], and twin girls [2.4 (0.5) kg] did not differ between types of conception. In the infant cohort in 3-month-old singletons, serum IGF-I was lower in ICSI [78 (26) ng/ml] than NC boys [94 (27) ng/ml, P < 0.001] and IVF [74 (34) ng/ml], compared with NC girls [93 (43) ng/ml, P = 0.011]. ICSI children were also smaller than their target height (sd score) at 3 yr of age [mean -0.91 (1.2)], compared with NC children [-0.61 (0.9), P = 0.033]. In the child cohort, target height attainment (sd score) and growth factors did not differ among the three groups. CONCLUSIONS:The overall growth pattern of ICSI and IVF children in both cohorts was normal. Our findings of subtle differences in target height attainment and serum IGF-I levels between infants born after assisted reproduction techniques and controls may not be clinically significant. However, these observations indicate that further systematic follow-up of growth and puberty in these children is needed.

背景与目标： 背景：人们对后代辅助生殖技术的安全性表示关注。
目的：本研究的目的是调查胞浆内精子注射（ICSI）和体外受精（IVF）后出生的儿童的出生后生长和生长因子。
设计：该研究有两个队列：一个基于人群的纵向婴儿队列0-36个月[236 ICSI，173 IVF，1530自然受孕（NC）]，以及一个横断面儿童队列，在5年时（68 ICSI，67 IVF ，70 NC）。
干预措施：分别在出生时，3、18、36（婴儿队列）和60个月（儿童队列）进行人体测量，并在3或60个月时采集血样。
主要观察指标：血清IGF-I，IGFBP-3，身高，体重，头围和腹围，体重指数和脂肪褶皱是主要的观察指标。
结果：人体测量结果显示，ICSI和IVF儿童与对照组之间均无显着差异。但是，单身ICSI女孩[3.4（0.6）千克，P = 0.008]的出生体重略低于IVF [3.5（0.5）千克]和NC女孩[3.5（0.5）千克]。单胎男孩[3.6（0.5）千克]，双胞胎男孩[2.6（0.6）千克]和双胞胎女孩[2.4（0.5）千克]的出生体重在不同的受孕类型之间没有差异。在3个月大的单胎婴儿队列中，ICSI的血清IGF-I低于NC男孩[94（27）ng / ml，P <0.001]和IVF [74（ 34）ng / ml]，而NC女生则为[93（43）ng / ml，P = 0.011]。与3岁儿童相比，ICSI儿童在3岁时也小于其目标身高（sd评分）[平均-0.91（1.2）]，而NC儿童则为[-0.61（0.9），P = 0.033]。在儿童队列中，三组之间的目标身高获得（sd得分）和生长因子没有差异。
结论：两组人群ICSI和IVF儿童的总体生长方式均正常。我们在辅助生殖技术和对照后出生的婴儿之间的目标高度获得和血清IGF-I水平细微差异的发现可能在临床上并不重要。但是，这些观察结果表明，需要对这些儿童的生长和青春期进行进一步的系统随访。

BACKGROUND & AIMS: OBJECTIVES:There are no direct comparisons of blood glucose values in samples collected with barrier serum tubes (SST) and NaF/potassium oxalate (NaF/KOx) plasma tubes. Collection of samples in SST tubes can offer considerable savings and specimen processing advantages for national level surveys. DESIGN AND METHODS:Serum and plasma samples were collected under 'field conditions' from a single draw of 3692 individuals participating in the Canadian Health Measures Survey. The samples were analyzed retrospectively using the VITROS GLU Slide method (glucose oxidase-based). RESULTS:There was a high rate of hemolysis in the NaF/KOx tubes (86.2%) while hemolysis was infrequently observed with the SST tubes (2%). Comparing only blood draws where no hemolysis was observed in both tubes (n=495; paired t-test) showed no effect of tube type on serum/plasma glucose concentrations. This was also observed when data was restricted to cases when only SST samples were not hemolyzed (n=3546; paired t-test). CONCLUSIONS:These data show that both collection tubes can be used under survey collection and processing conditions to measure glucose with our assay system with no difference in reported results.

背景与目标： 目的：尚无直接比较采用屏障血清试管（SST）和NaF /草酸钾（NaF / KOx）血浆试管收集的样本中血糖值的方法。在SST管中收集样品可以为国家级调查提供大量的节省和样品处理的优势。
设计与方法：在“现场条件”下从参加加拿大卫生措施调查的3692个人中抽取了血清和血浆样品。使用VITROS GLU Slide方法（基于葡萄糖氧化酶）对样品进行回顾性分析。
结果：NaF / KOx管的溶血率很高（86.2％），而SST管的溶血率很少（2％）。仅比较在两个试管中均未观察到溶血的抽血情况（n = 495；配对t检验）显示试管类型对血清/血浆葡萄糖浓度无影响。当数据仅限于仅不对SST样品进行溶血的情况时（n = 3546；配对t检验），也可以观察到这一点。
结论：这些数据表明，在我们的测定系统中，两个收集管均可在调查收集和处理条件下用于测量葡萄糖，报道的结果没有差异。

BACKGROUND & AIMS: BACKGROUND:To investigate the relationship between the levels of serum complement C1q and the risk and severity of acute ischemic stroke, a total of 154 patients with acute ischemic stroke and 42 healthy volunteers as normal controls were enrolled in the present study. METHODS:According to the onset time of stroke, patients were divided into three groups. Using an immune transmission turbidity method, the levels of serum complement C1q were detected to investigate the relationship between the level of serum complement C1q and the incidence and severity of acute ischemic stroke. The risk factors of these groups were calculated using a conditional logistic regression model. The assessment of neurological function impairment was carried out according to the National Institute of Health Stroke Scale. Then correlation anal- ysis was carried out between the level of serum complement C1q among patients with acute ischemic stroke and the degree of neurological function impairment. RESULTS:The results showed that the level of serum complement C1q was higher in the ischemic stroke group than in the control group. Using a conditional logistic regression model it was discovered that serum complement C1q was the independent pathogenic factor of cerebral infarction. There also was a decreasing trend in the level of serum complement C1q with the extension of the onset time and an increasing trend in the level of serum complement C1q with the increase in the maximum diameter of infarction volume. CONCLUSIONS:Serum complement C1q is an independent risk factor for acute outbreak of ischemic stroke, whose level is closely related to the outbreak and infarct size and neurological function impairment.

背景与目标： 背景：为了研究血清补体C1q水平与急性缺血性中风的风险和严重程度之间的关系，本研究共纳入154例急性缺血性中风患者和42名健康志愿者作为正常对照。
方法：根据中风的发作时间，将患者分为三组。采用免疫传递浊度法检测血清补体C1q水平，以探讨血清补体C1q水平与急性缺血性脑卒中的发生率和严重程度之间的关系。使用条件逻辑回归模型计算这些组的危险因素。根据美国国立卫生研究院卒中量表对神经功能损害进行评估。然后在急性缺血性卒中患者的血清补体C1q水平与神经功能损害程度之间进行相关分析。
结果：缺血性中风组血清补体C1q水平高于对照组。使用条件逻辑回归模型，发现血清补体C1q是脑梗死的独立致病因素。随着发作时间的延长，血清补体C1q的水平也有降低的趋势，并且随着梗死体积的最大直径的增加，血清补体C1q的水平也有增加的趋势。
结论：血清补体C1q是缺血性卒中急性发作的独立危险因素，其水平与发作，梗死面积和神经功能损害密切相关。

BACKGROUND & AIMS: :Recently, growing interest in vitamin D has emerged from findings that demonstrate a low vitamin D status in populations. Similarly, much interest has been shown in the role that anti-Müllerian hormone (AMH) plays in reproductive physiology. Considerable confusion as to whether vitamin D status is related to ovarian function can be found in the literature. Our retrospective study was performed from June 2014 to April 2015. Oocyte donors were recruited and stimulated under the antagonist protocol with gonadotrophin-releasing hormone (GnRH) agonist to trigger ovulation. In 851 stimulation cycles, we determined the association among serum total and bioavailable vitamin D levels, ovarian reserve and response to ovarian stimulation and the reproductive outcome in their recipients. We showed that vitamin D levels were unrelated to ovarian reserve or ovarian response after ovarian stimulation; in oocyte recipients, gestational outcome did not differ according to a donor's vitamin D serum status. No correlation was observed between serum AMH and vitamin D. Bioavailable vitamin D was not related to recipients' ongoing pregnancy rate. Highly prevalent vitamin D insufficiency neither impaired ovarian reserve nor response or oocyte quality in egg donors. No evidence was found for recommending the analysis of vitamin D status in oocyte donors.

背景与目标： ：最近，发现维生素D的人群中维生素D含量低的发现已引起人们对维生素D的日益增长的兴趣。同样，人们已经对抗苗勒氏管激素（AMH）在生殖生理中的作用表现出了极大的兴趣。关于维生素D状态是否与卵巢功能有关的大量混淆可以在文献中找到。我们的回顾性研究于2014年6月至2015年4月进行。在促性腺激素释放激素（GnRH）激动剂的拮抗方案下，募集卵母细胞供体并对其进行刺激以触发排卵。在851个刺激周期中，我们确定了血清总维生素D和生物有效性维生素D水平，卵巢储备以及对卵巢刺激的反应以及其受体的生殖结局之间的关联。我们发现维生素D水平与卵巢刺激后的卵巢储备或卵巢反应无关。在卵母细胞受体中，妊娠结果根据供体的维生素D血清状态而不同。血清AMH与维生素D之间没有相关性。可利用的维生素D与接受者的持续妊娠率无关。高度普遍的维生素D缺乏症既不损害卵子捐献者的卵巢储备，也不损害其反应或卵母细胞质量。没有证据表明建议对卵母细胞供体中的维生素D状况进行分析。

BACKGROUND & AIMS: BACKGROUND:Interleukin-17 (IL-17), which is secreted by Th17 cells, is a proinflammatory cytokine that is implicated in the pathogenesis of multiple sclerosis (MS) and plays a role in nonresponse of MS patients to interferon-β (IFN-β) therapy. OBJECTIVES:The purpose of this study was to establish a correlation between nonresponders (NR) and IL-17A serum titers and binding antibodies (BAbs) to IFN-β, as well as to find a correlation between IL-17A serum levels and other features of MS patients. METHODS:Our prospective study included 72 inactive relapsing-remitting multiple sclerosis (RRMS) patients that had been treated for at least 18 months with IFN-β and 15 healthy subjects. We determined the serum levels of IL-17A and of BAbs. IL-17A levels were considered elevated (IL-17A+) if the recorded value was greater than 1.6 pg/ml. RESULTS:Twenty-seven patients (37.5%) were NR and had a significantly higher serum IL-17A level compared to the responders group. Nineteen patients (26.4%) were IL-17A+ and had had a significantly higher number of relapses in the previous year and a higher Expanded Disability Status Score. The majority of IL-17A+ patients were NR and had a shorter MS duration. CONCLUSIONS:RRMS patients with high serum IL-17A levels do not respond well to IFN-β therapy and have shorter MS duration compared to patients with low IL-17A levels. This response is not influenced by the presence of BAbs.

背景与目标： 背景：Th17细胞分泌的白细胞介素17（IL-17）是一种促炎细胞因子，与多发性硬化症（MS）的发病机制有关，并且在MS患者对干扰素-β（IFN-α）无反应中起作用β）疗法。
目的：本研究的目的是建立无应答者（NR）与IL-17A血清滴度和针对IFN-β的结合抗体（BAbs）之间的相关性，以及找出IL-17A血清水平与其他特征之间的相关性MS患者。
方法：我们的前瞻性研究包括72例接受IFN-β治疗至少18个月的非活动性复发缓解型多发性硬化症（RRMS）患者和15名健康受试者。我们确定了IL-17A和BAbs的血清水平。如果记录值大于1.6 pg / ml，则认为IL-17A水平升高（IL-17A）。
结果：27名患者（37.5％）为NR，与应答者组相比，血清IL-17A水平显着更高。 19名患者（26.4％）为IL-17A，在前一年中复发率明显更高，而“扩展残疾状态评分”更高。大多数IL-17A患者为NR，MS病程较短。
结论：与低IL-17A水平的患者相比，血清IL-17A水平高的RRMS患者对IFN-β治疗的反应不佳，MS病程较短。该反应不受BAbs的存在的影响。

BACKGROUND & AIMS: :Differentiation-inducing factor-1 [1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one (DIF-1)] is an important regulator of cell differentiation and chemotaxis in the development of the cellular slime mold Dictyostelium discoideum However, the entire signaling pathways downstream of DIF-1 remain to be elucidated. To characterize DIF-1 and its potential receptor(s), we synthesized two fluorescent derivatives of DIF-1, boron-dipyrromethene (BODIPY)-conjugated DIF-1 (DIF-1-BODIPY) and nitrobenzoxadiazole (NBD)-conjugated DIF-1 (DIF-1-NBD), and investigated their biological activities and cellular localization. DIF-1-BODIPY (5 µM) and DIF-1 (2 nM) induced stalk cell differentiation in the DIF-deficient strain HM44 in the presence of cyclic adenosine monosphosphate (cAMP), whereas DIF-1-NBD (5 µM) hardly induced stalk cell differentiation under the same conditions. Microscopic analyses revealed that the biologically active derivative, DIF-1-BODIPY, was incorporated by stalk cells at late stages of differentiation and was localized to mitochondria. The mitochondrial uncouplers carbonyl cyanide m-chlorophenylhydrazone (CCCP), at 25-50 nM, and dinitrophenol (DNP), at 2.5-5 µM, induced partial stalk cell differentiation in HM44 in the presence of cAMP. DIF-1-BODIPY (1-2 µM) and DIF-1 (10 nM), as well as CCCP and DNP, suppressed chemotaxis in the wild-type strain Ax2 in shallow cAMP gradients. These results suggest that DIF-1-BODIPY and DIF-1 induce stalk cell differentiation and modulate chemotaxis, at least in part, by disturbing mitochondrial activity.

背景与目标： ：诱导分化因子-1 [1-（3,5-dichloro-2,6-dihydroxy-4-methoxymethoxy）hexan-1-one（DIF-1）]是发育过程中细胞分化和趋化性的重要调节剂细胞粘液霉菌盘基网柄菌的形成，然而，DIF-1下游的整个信号传导途径仍有待阐明。为了表征DIF-1及其潜在的受体，我们合成了DIF-1的两种荧光衍生物，硼二吡咯亚甲基（BODIPY）偶联的DIF-1（DIF-1-BODIPY）和硝基苯并二唑（NBD）偶联的DIF- 1（DIF-1-NBD），并研究了它们的生物学活性和细胞定位。在存在环磷酸单磷酸腺苷（cAMP）的情况下，DIF-1-BODIPY（5μm）和DIF-1（2μm）在DIF缺陷菌株HM44中诱导茎细胞分化，而DIF-1-NBD（5μm）几乎没有在相同条件下诱导茎细胞分化。显微分析表明，具有生物活性的衍生物DIF-1-BODIPY在分化后期被茎细胞掺入并定位于线粒体。线粒体解偶联剂羰基氰化物间氯苯hydr（CCCP）（25-50nM）和二硝基苯酚（DNP）（2.5-5μm）在cAMP存在下诱导HM44部分茎细胞分化。 DIF-1-BODIPY（1-2μM）和DIF-1（10μnM）以及CCCP和DNP在浅cAMP梯度中抑制了野生型菌株Ax2的趋化性。这些结果表明，DIF-1-BODIPY和DIF-1至少部分地通过干扰线粒体活性来诱导茎细胞分化并调节趋化性。

BACKGROUND & AIMS: :M-type phospholipase A2 receptor (PLA2R) is the major target antigen in primary membranous nephropathy (PMN). Previous studies have evaluated the diagnostic value of serum anti-PLA2R antibody. However, the correlation of serum anti-PLA2R antibody and glomerular PLA2R deposition, and their association with clinical characteristics need to be further evaluated.A total of 136 patients were involved as inception group because serum anti-PLA2R antibody and glomerular PLA2R antigen were simultaneously measured. We examined serum anti-PLA2R antibody by ELISA and glomerular PLA2R deposition by immunofluorescence assay.Positive serum anti-PLA2R antibody and glomerular PLA2R deposition were seen in 58.8% (80/136) and 95.6% (130/136) patients, respectively (P < .001). Proteinuria, serum total protein, serum albumin, serum creatinine, and estimated glomerular filtration rate (eGFR) had significant differences between patients with serum anti-PLA2R antibody and those without. Serum anti-PLA2R antibody levels were correlated with serum albumin, serum creatinine, eGFR, and proteinuria. Glomerular PLA2R deposition intensities were weakly correlated with proteinuria. Unexpectedly, there was a positive correlation rather than a negative correlation between glomerular PLA2R deposition intensity and eGFR.In conclusion, serum anti-PLA2R antibody is more closely correlated with disease activity and renal function than glomerular PLA2R deposition.

背景与目标： ：M型磷脂酶A2受体（PLA2R）是原发性膜性肾病（PMN）的主要靶抗原。先前的研究已经评估了血清抗PLA2R抗体的诊断价值。然而，血清抗PLA2R抗体与肾小球PLA2R沉积的相关性及其与临床特征的相关性需要进一步评估。由于同时检测了血清抗PLA2R抗体和肾小球PLA2R抗原，因此共有136例患者入组。 。我们通过ELISA检测了血清抗PLA2R抗体，并通过免疫荧光法检测了肾小球PLA2R沉积。分别在58.8％（80/136）和95.6％（130/136）患者中观察到阳性血清抗PLA2R抗体和肾小球PLA2R沉积（P <.001）。蛋白尿，血清总蛋白，血清白蛋白，血清肌酐和估计的肾小球滤过率（eGFR）在有血清抗PLA2R抗体的患者和没有血清抗PLA2R抗体的患者之间有显着差异。血清抗PLA2R抗体水平与血清​​白蛋白，血清肌酐，eGFR和蛋白尿相关。肾小球PLA2R沉积强度与蛋白尿弱相关。出乎意料的是，肾小球PLA2R沉积强度与eGFR之间呈正相关而非负相关。总之，血清抗PLA2R抗体与肾小球PLA2R沉积与疾病活动性和肾功能之间的相关性更高。

BACKGROUND & AIMS: :Vitamin D hormone (1,25-dihydroxyvitamin D) is involved in innate immunity and induces host defense peptides in epithelial cells, suggesting its involvement in mucosal defense against infections. Chlamydia trachomatis is a major cause of bacterial sexually transmitted disease worldwide. We tested the hypothesis that the vitamin D endocrine system would attenuate chlamydial infection. Vitamin D receptor knock-out mice (VDR(-/-)) and wild-type mice (VDR(+/+)) were infected with 10(3) inclusion forming units of Chlamydia muridarum and cervical epithelial cells (HeLa cells) were infected with C. muridarum at multiplicity of infection 5:1 in the presence and absence of 1,25-dihydroxyvitamin D3. VDR(-/-) mice exhibited significantly higher bacterial loading than wild-type VDR(+/+) mice (P<0.01) and cleared the chlamydial infection in 39 days, compared with 18 days for VDR(+/+) mice. Monocytes and neutrophils were more numerous in the uterus and oviduct of VDR(-/-) mice than in VDR(+/+) mice (P<0.05) at d 45 after infection. Pre-treatment of HeLa cells with 10nM or 100nM 1,25-dihydroxyvitamin D3 decreased the infectivity of C. muridarum (P<0.001). Several differentially expressed protein spots were detected by proteomic analysis of chlamydial-infected HeLa cells pre-treated with 1,25-dihydroxyvitamin D3. Leukocyte elastase inhibitor (LEI), an anti-inflammatory protein, was up-regulated. Expression of LEI in the ovary and oviduct of infected VDR(+/+) mice was greater than that of infected VDR(-/-) mice. We conclude that the vitamin D endocrine system reduces the risk for prolonged chlamydial infections through regulation of several proteins and that LEI is involved in its anti-inflammatory activity.

背景与目标： ：维生素D激素（1,25-二羟基维生素D）参与先天免疫，并诱导上皮细胞中的宿主防御肽，表明其参与了粘膜防御感染。沙眼衣原体是全世界细菌性传播疾病的主要原因。我们检验了维生素D内分泌系统会减轻衣原体感染的假设。维生素D受体敲除小鼠（VDR（-/-））和野生型小鼠（VDR（/））感染了衣原体衣原体的10（3）个包涵体形成单位，并感染了宫颈上皮细胞（HeLa细胞）在存在和不存在1,25-二羟基维生素D3的情况下，感染C. muridarum的感染复数为5：1。 VDR（-/-）小鼠比野生型VDR（/）小鼠表现出明显更高的细菌载量（P <0.01），并且在39天后清除了衣原体感染，而VDR（/）小鼠为18天。感染后第45天，VDR（-/-）小鼠的子宫和输卵管中的单核细胞和中性粒细胞比VDR（/）小鼠中的多（P <0.05）。用10nM或100nM 1,25-二羟基维生素D3预处理HeLa细胞可降低muridarum衣原体的感染性（P <0.001）。通过蛋白质组学分析衣原体感染的HeLa细胞经1,25-二羟基维生素D3预处理后，检测到了几个差异表达的蛋白斑点。白细胞弹性蛋白酶抑制剂（LEI），一种抗炎蛋白，被上调。 LEI在受感染的VDR（/）小鼠的卵巢和输卵管中的表达大于受感染的VDR（-/-）小鼠的表达。我们得出的结论是，维生素D内分泌系统通过调节几种蛋白质降低了衣原体长时间感染的风险，并且LEI参与了其抗炎活性。

BACKGROUND & AIMS: :The neuropeptide calcitonin gene-related peptide (CGRP) plays a critical role in the pathophysiology of migraine. We have focused on the role of CGRP in photophobia, which is a common migraine symptom. We previously used an operant-based assay to show that CGRP-sensitized transgenic (nestin/hRAMP1), but not control, mice exhibited light aversion in response to an intracerebroventricular CGRP injection. A key question was whether the transgenic phenotype was due to overexpression of the CGRP receptor at endogenous or novel expression sites. We reasoned that if endogenous receptor sites were sufficient for light-aversive behavior, then wild-type mice should also show the phenotype when given a sufficiently strong stimulus. In this study, we report that mice with normal levels of endogenous CGRP receptors demonstrate light avoidance following CGRP administration. This phenotype required the combination of two factors: higher light intensity and habituation to the testing chamber. Control tests confirmed that light aversion was dependent on coincident exposure to CGRP and light and cannot be fully explained by increased anxiety. Furthermore, CGRP reduced locomotion only in the dark, not in the light. Coadministration of rizatriptan, a 5-HT(1B/D) agonist anti-migraine drug, attenuated the effects of exogenous CGRP on light aversion and motility. This suggests that triptans can act by mechanisms that are distinct from inhibition of CGRP release. Thus, we demonstrate that activation of endogenous CGRP receptors is sufficient to elicit light aversion in mice, which can be modulated by a drug commonly used to treat migraine.

背景与目标： ：神经肽降钙素基因相关肽（CGRP）在偏头痛的病理生理中起关键作用。我们集中于CGRP在畏光中的作用，这是一种常见的偏头痛症状。我们以前使用基于操作员的测定法来显示CGRP致敏的转基因小鼠（nestin / hRAMP1）而非对照小鼠表现出对脑室内CGRP注射的反感。一个关键问题是转基因表型是否是由于内源或新表达位点上CGRP受体的过度表达所致。我们认为，如果内源性受体位点足以进行光平均行为，那么当给予足够强的刺激时，野生型小鼠也应表现出表型。在这项研究中，我们报告内源性CGRP受体水平正常的小鼠在CGRP给药后表现出避光作用。该表型需要两个因素的结合：较高的光强度和对测试室的适应性。对照测试证实，厌恶光取决于同时接触CGRP和光照，不能通过焦虑增加充分解释。此外，CGRP仅在黑暗中而不是在光线下减少运动。利扎曲普坦（5-HT（1B / D）激动剂抗偏头痛药物）的共同给药减弱了外源性CGRP对避光和运动的影响。这表明曲普坦可以通过不同于抑制CGRP释放的机制起作用。因此，我们证明内源性CGRP受体的激活足以在小鼠中引起避光，这可以通过通常用于治疗偏头痛的药物进行调节。

BACKGROUND & AIMS: :Objective: To determine the effect of electro-acupuncture (EA) treatment on serum levels of interferon-γ (IFN-γ) in rats with 7,12-dimethylbenz(α)anthracene (DMBA)-induced breast tumors. Methods: Twenty five female Wistar rats were divided randomly into 5 groups: normal group (N; neither DMBA-induced nor treated with EA); control group (C; DMBA-induced only); EA 3 days : (DMBA-induced + EA for 3 days); EA 5 days: (DMBA-induced + EA for 5 days); EA 10 days: (DMBA-induced + EA for 10 days) group. Animals were acclimatized from day 1 to day 7. Subcutaneus injections of DMBA 10mg/kg BW was administered every second day, from days 7 to 35. Acupuncture was performed every second day from day 42. Rats were sacrificed on the second day after the last acupuncture, breast tumors excised and stained histological sections were analysed by light microscopy. At sacrifice, blood was extracted from the heart for measurement of serum IFN-γ by ELISA. Results: All of the DMBA-induced rats developed tumors. Electro-acupuncture significantly increased IFN-γ levels in DMBA induced rats, when compared to control group. Conclusions: Our findings suggest that EA significantly increases IFN-γ levels in DMBA-induced breast tumors.

背景与目标： ：目的：确定电针治疗对血清中干扰素-γ（IFN-γ）水平的影响
在患有7,12-二甲基苯并（α）蒽（DMBA）诱导的乳腺肿瘤的大鼠中。方法：25名女性Wistar
将大鼠随机分为5组：正常组（N；既不是DMBA诱导的，也不是用EA治疗的）。控制
组（C；仅DMBA诱导）； EA 3天：（DMBA诱导的EA 3天）； EA 5天：（DMBA诱导的EA
5天）; EA 10天：（DMBA诱导的EA 10天）组。从第1天到第7天使动物适应环境。
从第二天到第7天至第35天，皮下注射DMBA 10mg / kg体重。
从第42天起每隔第二天进行一次。最后一次针刺后第二天将大鼠处死，
通过光学显微镜分析切除的肿瘤和染色的组织学切片。牺牲时，血液被抽出
从心脏通过ELISA测定血清IFN-γ。结果：所有DMBA诱导的大鼠均出现肿瘤。
与对照组相比，电针显着增加了DMBA诱导的大鼠的IFN-γ水平。
结论：我们的发现表明，EA可以显着增加DMBA诱导的乳腺肿瘤中的IFN-γ水平。

BACKGROUND & AIMS: Context:Vitamin D deficiency patients have an increased cardiovascular (CV) morbidity and mortality. Carotid intima-media thickness (IMT) and carotid plaques are markers of subclinical atherosclerosis and predictors of CV events. Objective:To perform a meta-analysis of studies evaluating the impact of Vitamin D deficiency on common carotid artery IMT (CCA-IMT) and on the prevalence of carotid plaques. Data Sources:Studies were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. Results:Twenty-one studies (3,777 Vitamin D deficiency patients and 4,792 controls) with data on CCA-IMT and 6 studies (1,889 Vitamin D deficiency patients and 2,883 controls) on the prevalence of carotid plaques were included. Compared to controls, Vitamin D deficiency patients showed a significantly higher CCA-IMT (mean difference [MD]: 0.043 mm; 95%CI: 0.030, 0.056; P<0.001), and an increased prevalence of carotid plaques (Odds Ratio [OR]: 2.29, 95%CI: 1.03-5.11; P=0.043) with an attributable risk of 35.9%. When selecting studies specifically including patients with diabetes, the prevalence of carotid plaques in Vitamin D deficiency patients than in controls resulted higher (OR: 3.27; 95%CI: 1,62-6.62; P=0.001). A significant difference in CCA-IMT was confirmed when comparing patients with Vitamin D insufficiency to controls (MD: 0.011; 95%CI: 0.010-0.012, P<0.001). Sensitivity analyses substantially confirmed results and regression models showed that with the exception of LDL-cholesterol, HDL-cholesterol, triglycerides and the prevalence of hypercholesterolemia, all the other clinical and demographic co-variates significantly impacted on the difference in CCA-IMT between Vitamin D deficiency patients and controls. Conclusions:Both Vitamin D deficiency and Vitamin D insufficiency are associated with subclinical atherosclerosis, potentially suggesting an increased CV risk in these clinical settings.

背景与目标： 背景：维生素D缺乏症患者的心血管（CV）发病率和死亡率增加。颈动脉内膜中层厚度（IMT）和颈动脉斑块是亚临床动脉粥样硬化的标志物和CV事件的预测因子。
目的：进行荟萃分析，评估维生素D缺乏对颈总动脉IMT（CCA-IMT）和颈动脉斑块患病率的影响。
数据来源：在PubMed，Web of Science，Scopus和EMBASE数据库中系统地搜索了研究。
结果：包括21项研究（3,777例维生素D缺乏症患者和4,792例对照者）的CCA-IMT数据和6项研究（1,889例D维生素D缺乏症患者和2,883例对照者）的颈动脉斑块患病率。与对照组相比，维生素D缺乏症患者的CCA-IMT显着更高（平均差异[MD]：0.043毫米； 95％CI：0.030，0.056； P <0.001），并且颈动脉斑块的患病率增加（几率[OR] ]：2.29，95％CI：1.03-5.11； P = 0.043），归因风险为35.9％。在选择专门针对糖尿病患者的研究时，维生素D缺乏症患者的颈动脉斑块患病率高于对照组（OR：3.27； 95％CI：1,62-6.62； P = 0.001）。当将维生素D功能不足的患者与对照组进行比较时，证实了CCA-IMT的显着差异（MD：0.011； 95％CI：0.010-0.012，P <0.001）。敏感性分析基本证实了结果，回归模型显示，除了低密度脂蛋白胆固醇，高密度脂蛋白胆固醇，甘油三酸酯和高胆固醇血症的患病率外，所有其他临床和人口统计学共同变量均显着影响维生素D之间CCA-IMT的差异缺乏患者和对照。
结论：维生素D缺乏症和维生素D缺乏症均与亚临床动脉粥样硬化有关，可能提示在这些临床情况下CV风险增加。

BACKGROUND & AIMS: :Dermatophagoides farinae-, ovalbumin- and lactalbumin-specific IgG, IgG1, IgG4, IgA and IgM were evaluated in 161 healthy children [Group 1], 84 children with bronchial asthma and/or allergic rhinitis but without atopic dermatitis [Group 2], and 54 children with atopic dermatitis but without bronchial asthma and allergic rhinitis [Group 3]. We also studied D. farinae-, egg-white-, and milk-specific IgE of children with allergic diseases. D. farinae-specific IgG, IgG1, IgG4 and IgA in Groups 2 and 3 increased until 5 years of age and thereafter they remained constant. After 2 years of age, D. farinae-specific IgG, IgG1, IgG4 and IgA in Group 2 were higher than those in Groups 1 and 3. Ovalbumin- and lactalbumin-specific IgG, IgG1, IgG4 and IgA in Groups 2 and 3 increased until 1 year of age and thereafter decreased. Until 1 year of age, ovalbumin- and lactalbumin-specific IgG, IgG1 and IgG4 in Groups 3 were higher than those in Groups 1 and 2. D. farinae-, ovalbumin- and lactalbumin-specific IgM were constant in all ages of all groups. These results suggest that atopic dermatitis in young children is related to food-specific immunoglobulins and that respiratory allergic diseases in older children is related to D. farinae-specific immunoglobulins.

背景与目标： ：在161名健康儿童（第1组），84例支气管哮喘和/或过敏性鼻炎但无特应性皮炎的儿童（第2组）中评估了粉状皮癣，卵白蛋白和乳白蛋白特异性IgG，IgG1，IgG4，IgA和IgM。 54例患特应性皮炎但无支气管哮喘和过敏性鼻炎的儿童[3组]。我们还研究了患有过敏性疾病的儿童的D. farinae，蛋清和牛奶特异性IgE。第2组和第3组中的D. farinae特异性IgG，IgG1，IgG4和IgA升高至5岁，此后保持恒定。 2岁后，第2组的粉虱D. farinae特异性IgG，IgG1，IgG4和IgA高于第1和3组。第2和第3组的卵白蛋白和乳白蛋白特异性IgG，IgG1，IgG4和IgA增加。直到1岁，此后有所减少。直到1岁之前，第3组中卵白蛋白和乳白蛋白特异性IgG，IgG1和IgG4高于第1组和第2组。粉虱，卵白蛋白和乳白蛋白特异性IgM在所有组的所有年龄中均保持不变。 。这些结果表明，幼儿的特应性皮炎与食物特异性免疫球蛋白有关，而年龄较大的儿童的呼吸道过敏性疾病与D. farinae特异性免疫球蛋白有关。

BACKGROUND & AIMS: OBJECTIVE:To explore the prognostic value of the postsurgical half-life (HL) of serum alpha-fetoprotein (AFP). BACKGROUND:There is still a paucity of early surrogate indicators of clinical endpoints after liver resection of hepatocellular carcinoma (HCC). METHODS:The analysis was based on cohorts of 225 (exploration set) and 117 (validation set) treatment-naïve HCC patients undergoing curative liver resection. We defined 3 categories of AFP HL: early complete resolution of AFP, normal HL, and prolonged HL if the HL exceeded 7 days. Overall, probabilities of recurrence and survival were estimated and compared across the AFP HL categories. RESULTS:In the exploration cohort, 48 patients (21.3%) achieved early AFP complete resolution, 116 (51.6%) had normal HL, and 61 (27.1%) had prolonged HL. Long AFP HL was significantly associated with early postoperative recurrence (P < 0.001), as was microvascular invasion. Early recurrence within 2 years of resection was observed in 59% of the patients with prolonged AFP HL compared with only 29.3% of those with normal AFP HL (P < 0.001). A log-rank test followed by multivariate Cox analysis identified an independent function of prolonged AFP HL in predicting shorter recurrence-free survival and overall survival time after HCC resection (hazard ratios, 2.81 and 3.58; P < 0.001). When AFP HL analysis was applied to the validation cohort, the association between prolonged AFP HL and survival endpoints (hazard ratio, 11.63 and 16.39; P < 0.001) was confirmed.

背景与目标： 目的：探讨血清甲胎蛋白（AFP）的术后半衰期（HL）的预后价值。
背景：肝切除肝细胞癌（HCC）后仍缺乏临床终点的早期替代指标。
方法：该分析基于225例（探索组）和117例（验证组）未进行过根治性肝切除的未接受治疗的HCC患者的分析。我们定义了AFP HL的3个类别：AFP的早期完全消退，正常HL和如果HL超过7天则延长HL。总体而言，估计并比较了AFP HL类别中复发和存活的可能性。
结果：在探索队列中，有48例（21.3％）的患者达到了AFP的早期完全缓解，HL正常的116例（51.6％），HL延长的61例（27.1％）。长期AFP HL与微血管浸润与术后早期复发显着相关（P <0.001）。 AFP HL延长的患者中有59％的患者在切除的2年内出现了早期复发，而AFP HL正常的患者中只有29.3％的患者出现了早期复发（P <0.001）。对数秩检验和随后的多元Cox分析确定了AFP HL延长在预测肝癌切除术后较短的无复发生存期和总生存期方面具有独立的功能（危险比，2.81和3.58； P <0.001）。当将AFP HL分析应用于验证队列时，证实了延长的AFP HL与生存终点之间的关联（危险比：11.63和16.39； P <0.001）。

BACKGROUND & AIMS: BACKGROUND:Left atrial enlargement, a sensitive integrator of left ventricular diastolic function, is associated with increased cardiovascular morbidity and mortality. Vitamin D is linked to lower cardiovascular morbidity, possibly modifying cardiac structure and function; however, firm evidence is lacking. We assessed the effect of an activated vitamin D analog on left atrial volume index (LAVi) in a post hoc analysis of the PRIMO trial (clinicaltrials.gov: NCT00497146). METHODS AND RESULTS:One hundred ninety-six patients with chronic kidney disease (estimated glomerular filtration rate 15-60 mL/min per 1.73 m(2)), mild to moderate left ventricular hypertrophy, and preserved ejection fraction were randomly assigned to 2 μg of oral paricalcitol or matching placebo for 48 weeks. Two-dimensional echocardiography was obtained at baseline and at 24 and 48 weeks after initiation of therapy. Over the study period, there was a significant decrease in LAVi (-2.79 mL/m(2), 95% CI -4.00 to -1.59 mL/m(2)) in the paricalcitol group compared with the placebo group (-0.70 mL/m(2) [95% CI -1.93 to 0.53 mL/m(2)], P = .002). Paricalcitol also attenuated the rise in levels of brain natriuretic peptide (10.8% in paricalcitol vs 21.3% in placebo, P = .02). For the entire population, the change in brain natriuretic peptide correlated with change in LAVi (r = 0.17, P = .03). CONCLUSIONS:Forty-eight weeks of therapy with an active vitamin D analog reduces LAVi and attenuates the rise of BNP. In a population where only few therapies alter cardiovascular related morbidity and mortality, these post hoc results warrant further confirmation.

背景与目标： 背景：左心房扩大，左心室舒张功能的敏感积分，与心血管疾病的发病率和死亡率增加有关。维生素D与降低心血管疾病的发病率有关，可能会改变心脏的结构和功能。但是，缺乏确凿的证据。我们在PRIMO试验的事后分析（clinicaltrials.gov：NCT00497146）中评估了活化的维生素D类似物对左心房体积指数（LAVi）的作用。
方法和结果：196例慢性肾脏病患者（估计肾小球滤过率每1.73 m（2）为15-60 mL / min），轻度至中度左心室肥厚和保留射血分数被随机分配为2μg口服paricalcitol或相匹配的安慰剂治疗48周。在治疗开始后的基线以及第24和48周获得了二维超声心动图。在研究期内，与安慰剂组（-0.70 mL）相比，paricalcitol组的LAVi（-2.79 mL / m（2），95％CI -4.00至-1.59 mL / m（2））显着降低。 / m（2）[95％CI -1.93至0.53 mL / m（2）]，P = .002）。 Paricalcitol还可以减轻脑钠肽水平的升高（paricalcitol中10.8％，而安慰剂中21.3％，P = .02）。对于整个人群，脑钠肽的变化与LAVi的变化相关（r = 0.17，P = .03）。
结论：用活性维生素D类似物治疗四十八周可降低LAVi并减轻BNP的升高。在只有少数几种疗法能改变与心血管有关的发病率和死亡率的人群中，这些事后结果值得进一步证实。