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Bone Geometry and Microarchitecture Deficits in Children with Alagille Syndrome. 儿童Alagille综合征的骨几何结构和微结构缺陷。
Pub Date : 2019-07-31 DOI: 10.1530/boneabs.7.p63
J. Kindler, Ellen L. Mitchell, D. Piccoli, A. Grimberg, M. Leonard, K. Loomes, B. Zemel
Alagille syndrome (ALGS) is an autosomal dominant disorder attributed to mutations in the Notch signaling pathway. Children with ALGS are at increased risk for fragility fracture of unknown etiology. Our objective was to characterize bone mass, geometry, and microarchitecture in children with ALGS. This was a cross-sectional study of 10 children (9 females), ages 8-18 years, with a clinical diagnosis of ALGS. Bone density was assessed via DXA (Hologic Discovery A) at several skeletal regions. Tibia trabecular and cortical bone was assessed via pQCT (Stratec XCT 2000) at the distal 3% and 38% sites, respectively. Tibia bone microarchitecture was assessed via HR-pQCT (Scanco XtremeCT II) at an ultradistal site located at 4% of tibia length and a cortical site at 30% of tibia length. Z-scores were calculated for DXA and pQCT measures. In the absence of XtremeCT II HR-pQCT reference data, these outcome measures were descriptively compared to a sample of healthy children ages 5-20 years (n=247). Anthropometrics and labs were also collected. Based on one-sample t-tests, mean Z-scores for height and weight (both p<0.05), were significantly less than zero. DXA bone Z-scores were not significantly different from zero, but were highly variable. For pQCT bone measures, Z-scores for total bone mineral content at the distal 3% site and cortical bone mineral content, cortical area, and cortical thickness at the distal 38% site were significantly less than zero (all p<0.05). There was good correspondence between pQCT measures of cortical thickness Z-scores and DXA Z-scores for aBMD at the whole body less head, 1/3 radius, and femoral neck (all p<0.05). Compared to healthy children, those with ALGS generally had lower trabecular number and greater trabecular separation despite having greater trabecular thickness (measured via HR-pQCT). Bilirubin and bile acids, markers of hepatic cholestasis, were associated with poorer bone measures. For example, greater bilirubin was associated with lower trabecular number (Spearman's rho [ρ]=-0.82, p=0.023) and greater trabecular separation (ρ=0.82, p=0.023) measured via HR-pQCT, and greater bile acids were associated with lower cortical area measured via pQCT (ρ=-0.78, p=0.041) and lower serum insulin-like growth factor-1 (ρ=-0.86, p=0.002). In summary, deficits in cortical bone size and trabecular bone microarchitecture were evident in children with ALGS. Further investigation is needed to understand the factors contributing to these skeletal inadequacies, and the manner in which these deficits contribute to increased fracture risk.
Alagille综合征(ALGS)是一种常染色体显性遗传病,归因于Notch信号通路突变。患有ALGS的儿童发生原因不明的脆性骨折的风险增加。我们的目的是表征ALGS儿童的骨量、几何形状和微结构。这是一项横断面研究,10名儿童(9名女性),年龄8-18岁,临床诊断为ALGS。在几个骨骼区域通过DXA (Hologic Discovery A)评估骨密度。胫骨小梁和皮质骨分别通过pQCT (strategy XCT 2000)在远端3%和38%的位置进行评估。通过HR-pQCT (Scanco XtremeCT II)在位于胫骨长度4%的超远端部位和位于胫骨长度30%的皮质部位评估胫骨骨微结构。计算DXA和pQCT测量的z分数。在缺乏XtremeCT II HR-pQCT参考数据的情况下,将这些结局指标与5-20岁健康儿童样本(n=247)进行描述性比较。还收集了人体测量和实验室数据。基于单样本t检验,身高和体重的平均z分数(p均<0.05)显著小于零。DXA骨z评分与0无显著差异,但差异很大。对于pQCT骨测量,远端3%部位的总骨矿物质含量和远端38%部位的皮质骨矿物质含量、皮质面积和皮质厚度的z评分均显著小于零(均p<0.05)。pQCT测量的皮质厚度z -评分与全身、1/3半径和股骨颈的aBMD的DXA z -评分之间有很好的对应关系(均p<0.05)。与健康儿童相比,ALGS患者的小梁数量更少,小梁分离更大,尽管小梁厚度更大(通过HR-pQCT测量)。胆红素和胆汁酸,肝脏胆汁淤积的标志,与较差的骨质测量有关。例如,高胆红素与低小梁数(Spearman's ρ= -0.82, p=0.023)和高小梁分离(ρ=0.82, p=0.023)相关,高胆红酸与pQCT测量的低皮质面积(ρ=-0.78, p=0.041)和低血清胰岛素样生长因子-1 (ρ=-0.86, p=0.002)相关。总之,在ALGS儿童中,皮质骨大小和骨小梁微结构的缺陷是明显的。需要进一步的研究来了解导致这些骨骼缺陷的因素,以及这些缺陷导致骨折风险增加的方式。
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引用次数: 8
Sex differences in the longitudinal associations between body composition and bone stiffness index in European children and adolescents. 欧洲儿童和青少年身体组成和骨僵硬指数之间纵向关联的性别差异。
Pub Date : 2019-07-31 DOI: 10.1530/boneabs.7.p107
Lan Cheng, H. Pohlabeln, W. Ahrens, P. Russo, T. Veidebaum, C. Chadjigeorgiou, D. Molnár, G. Eiben, S. de Henauw, L. Moreno, A. Page, A. Hebestreit
Fat mass (FM) and fat free mass (FFM) may influence bone health differentially. However, existing evidences on associations between FM, FFM and bone health are inconsistent and vary according to sex and maturity. The present study aims to evaluate longitudinal associations between FM, FFM and bone stiffness index (SI) among European children and adolescents with 6 years follow-up. A sample of 2468 children from the IDEFICS/I.Family was included, with repeated measurements of SI using calcaneal quantitative ultrasound, body composition using skinfold thickness, sedentary behaviors and physical activity using self-administrated questionnaires. Regression coefficients (β) and 99%-confidence intervals (99% CI) were calculated by sex-specified generalized linear mixed effects models to analyze the longitudinal associations between FM and FFM z-scores (zFM and zFFM) and SI percentiles, and to explore the possible interactions between zFM, zFFM and maturity. Baseline zFFM was observed to predict the change in SI percentiles in both boys (β = 4.57, 99% CI: 1.36, 7.78) and girls (β = 3.42, 99% CI: 0.05, 6.79) after 2 years. Moreover, baseline zFFM (β = 8.72, 99% CI: 3.18, 14.27 in boys and β = 5.89, 99% CI: 0.34, 11.44 in girls) and the change in zFFM (β = 6.58, 99% CI: 0.83, 12.34 in boys and β = 4.81, 99% CI: -0.41, 10.02 in girls) were positively associated with the change in SI percentiles after 6 years. In contrast, a negative association was observed between the change in zFM and SI percentiles in boys after 6 years (β = -3.70, 99% CI: -6.99, -0.42). Besides, an interaction was observed between the change in zFM and menarche on the change in SI percentiles in girls at 6 years follow-up (p = .009), suggesting a negative association before menarche while a positive association after menarche. Our findings support the existing evidences for a positive relationship between FFM and SI during growth. Furthermore, long-term FM gain was inversely associated with SI in boys, whereas opposing associations were observed across menarche in girls.
脂肪量(FM)和无脂肪量(FFM)可能对骨骼健康产生不同的影响。然而,关于FM、FFM与骨骼健康之间关系的现有证据是不一致的,并且根据性别和成熟度而不同。本研究旨在评估欧洲6岁儿童和青少年的FM、FFM和骨硬度指数(SI)之间的纵向相关性 年随访。来自IDEFICS/I的2468名儿童样本。纳入家庭,使用跟骨定量超声重复测量SI,使用皮褶厚度重复测量身体成分,使用自我管理问卷重复测量久坐行为和体育活动。通过性别指定的广义线性混合效应模型计算回归系数(β)和99%置信区间(99%CI),以分析FM和FFM z评分(zFM和zFFM)与SI百分位数之间的纵向关联,并探索zFM、zFFM与成熟度之间可能的相互作用。观察基线zFFM来预测两个男孩的SI百分位数的变化(β = 4.57,99%CI:1.36,7.78)和女孩(β = 3.42,99%置信区间:0.05,6.79) 年。此外,基线zFFM(β = 8.72,99%CI:3.18,14.27男孩和β = 5.89,99%CI:0.34,11.44)和zFFM的变化(β = 6.58,99%置信区间:男孩0.83,12.34,β = 4.81,99%的CI:女孩为-0.41,10.02)与6后SI百分位数的变化呈正相关 年。相反,男孩6岁后zFM和SI百分位数的变化呈负相关 年(β = -3.70,99%CI:6.99,-0.42)。此外,在zFM和月经初潮之间观察到女孩6岁时SI百分位数的变化 年随访(p = .009),表明在月经初潮前呈负相关,而在月经初初潮后呈正相关。我们的研究结果支持了生长过程中FFM和SI之间正相关的现有证据。此外,男孩的长期FM增益与SI呈负相关,而女孩的月经初潮则相反。
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引用次数: 5
Growth, enzymatic glutathione peroxidase activity and biochemical status of juvenile barramundi (Lates calcarifer) fed dietary fermented soybean meal and organic selenium. 以发酵豆粕和有机硒为饲料的金目鲈幼鱼的生长、酶谷胱甘肽过氧化物酶活性和生化状况。
IF 2.9 Pub Date : 2017-06-01 Epub Date: 2016-12-27 DOI: 10.1007/s10695-016-0331-2
I Ilham, Ravi Fotedar

Solvent-extracted soybean meal (SBM) was fermented using baker's yeast Saccharomyces cerevisae at 30 °C for 5 days. Four isonitrogenous and isocaloric diets containing 75% SBM protein, either fermented or non-fermented (SBM and FSBM), and supplemented or not with organic Se (OS) (SBMOS and FSBMOS), were fed to triplicate groups of juvenile barramundi (Lates calcarifer) (initial weight of 5 g) for 75 days. A fishmeal (FM)-based diet formulated for juvenile barramundi was used as a reference diet. The growth of fish was significantly affected by either the interaction of SBM type or by the OS level. In fish fed diets supplemented with OS (SBMOS and FSBMOS), final weight (FW), specific growth rate (SGR) and weight gain (WG) were higher in fish fed the fermented SBM (FSBMOS) than in those fed the non-fermented SBM (SBMOS). The apparent digestibility coefficient (ADC) of protein was higher in the fish fed the fermented SBM, either supplemented or unsupplemented with OS. However, there were no significant differences in the ADC of dry matter (DM) and lipids among the tested diets and in comparison to the reference diet. The haematocrit and leucocrit of fish fed the FSBMOS diet were lower than those of fish fed the FM diet. Furthermore, glutathione peroxidase (GPx) activity was significantly influenced by OS supplementation in the experimental diets; GPx activity was greater in the fish fed diets supplemented with OS. Creatinine kinase (CK) of all groups of fish was higher than the CK of those fed the reference diet. These results suggest that with a proper nutritional level, OS supplementation may act as an important factor in enzymatic GPx activity and in the haematology and blood biochemistry status of juvenile barramundi fed fermented SBM-based diets, encouraging improvement of the overall growth performance.

使用面包酵母在 30 °C 下发酵溶剂提取的豆粕(SBM)5 天。将含有 75% SBM 蛋白质的发酵或未发酵(SBM 和 FSBM)、添加或不添加有机硒(OS)(SBMOS 和 FSBMOS)的四种等氮等热量日粮喂给一式三组的金目鲈幼鱼(初始体重为 5 克),喂养 75 天。以鱼粉(FM)为基础配制的幼鱼日粮作为参考日粮。鱼类的生长受到 SBM 类型或 OS 水平的交互影响。在饲喂添加 OS 的日粮(SBMOS 和 FSBMOS)的鱼类中,饲喂发酵 SBM(FSBMOS)的鱼类的最终体重(FW)、特定生长率(SGR)和增重(WG)均高于饲喂非发酵 SBM(SBMOS)的鱼类。饲喂发酵 SBM(添加或不添加 OS)的鱼的蛋白质表观消化系数(ADC)更高。然而,不同试验日粮的干物质(DM)和脂类的表观消化系数与参考日粮相比没有明显差异。饲喂 FSBMOS 日粮的鱼的血细胞比容和白细胞比容低于饲喂 FM 日粮的鱼。此外,谷胱甘肽过氧化物酶(GPx)的活性受试验日粮中补充 OS 的显著影响;喂食补充 OS 的日粮的鱼的 GPx 活性更高。各组鱼的肌酸激酶(CK)均高于饲喂参考日粮的鱼。这些结果表明,在营养水平适当的情况下,补充 OS 可作为一个重要因素,促进以发酵 SBM 为基础的日粮饲喂的幼年金目鲈的 GPx 酶活性以及血液学和血液生化状况,从而提高其整体生长性能。
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引用次数: 1
The equilibrium of ubiquitination and deubiquitination at PLK1 regulates sister chromatid separation. PLK1 的泛素化和去泛素化平衡调节姐妹染色单体的分离。
IF 8 Pub Date : 2017-06-01 Epub Date: 2017-02-10 DOI: 10.1007/s00018-017-2457-5
Junjun Liu, Chuanmao Zhang

PLK1 regulates almost every aspect of mitotic events, including mitotic entry, spindle assembly, chromosome alignment, sister chromatid segregation, metaphase-anaphase transition, cytokinesis, etc. In regulating the chromosome alignment and sister chromatid segregation, PLK1 has to be localized to and removed from kinetochores at the right times, and the underlying mechanism that regulates PLK1 both spatially and temporally only became clearer recently. It has been found that deubiquitination and ubiquitination of PLK1 are responsible for its localization to and dissociation from the kinetochores, respectively. The equilibrium of this ubiquitination and deubiquitination plays an important role in regulating proper chromosome alignment and timely sister chromatid segregation. Here, we summarize and discuss the recent findings in investigating the spatial and temporal regulation of PLK1 during chromosome alignment and sister chromatid segregation.

PLK1几乎调控有丝分裂事件的各个方面,包括有丝分裂进入、纺锤体组装、染色体排列、姐妹染色单体分离、中期-后期转变、细胞质分裂等。在调节染色体排列和姐妹染色单体分离的过程中,PLK1必须在合适的时间定位到着丝点并从着丝点移出,而调控PLK1在空间和时间上的潜在机制直到最近才变得更加清晰。研究发现,PLK1的去泛素化和泛素化分别是其定位于着丝点和从着丝点分离的原因。这种泛素化和去泛素化的平衡在调节染色体正确排列和姐妹染色单体及时分离中起着重要作用。在此,我们总结并讨论了PLK1在染色体排列和姐妹染色单体分离过程中时空调控的最新研究结果。
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引用次数: 0
The Enigma of Poor Performance by Adults With Cochlear Implants. 佩戴人工耳蜗的成年人表现不佳之谜。
IF 2.1 Pub Date : 2016-12-01 DOI: 10.1097/MAO.0000000000001211
Aaron C Moberly, Chelsea Bates, Michael S Harris, David B Pisoni

Objective: Considerable unexplained variability and large individual differences exist in speech recognition outcomes for postlingually deaf adults who use cochlear implants (CIs), and a sizeable fraction of CI users can be considered "poor performers." This article summarizes our current knowledge of poor CI performance, and provides suggestions to clinicians managing these patients.

Method: Studies are reviewed pertaining to speech recognition variability in adults with hearing loss. Findings are augmented by recent studies in our laboratories examining outcomes in postlingually deaf adults with CIs.

Results: In addition to conventional clinical predictors of CI performance (e.g., amount of residual hearing, duration of deafness), factors pertaining to both "bottom-up" auditory sensitivity to the spectro-temporal details of speech, and "top-down" linguistic knowledge and neurocognitive functions contribute to CI outcomes.

Conclusions: The broad array of factors that contribute to speech recognition performance in adult CI users suggests the potential both for novel diagnostic assessment batteries to explain poor performance, and also new rehabilitation strategies for patients who exhibit poor outcomes. Moreover, this broad array of factors determining outcome performance suggests the need to treat individual CI patients using a personalized rehabilitation approach.

目的:使用人工耳蜗(CI)的语后聋成人在语音识别结果方面存在大量无法解释的差异和巨大的个体差异,相当一部分 CI 用户可被视为 "表现不佳者"。本文总结了我们目前对 CI 差异表现的认识,并为管理这些患者的临床医生提供了建议:方法:本文回顾了有关听力损失成人语音识别变异性的研究。方法:本文回顾了有关成人听力损失患者语音识别变异性的研究,并通过我们实验室最近对使用人工耳蜗的语后聋成人患者的研究结果进行了补充:结果:除了 CI 性能的传统临床预测因素(如残余听力、耳聋持续时间)外,"自下而上 "的听觉灵敏度对语音的频谱-时间细节以及 "自上而下 "的语言知识和神经认知功能都是影响 CI 效果的因素:影响成人 CI 用户语音识别能力的一系列因素表明,新型诊断评估电池既有可能解释不良表现,也有可能为表现出不良结果的患者提供新的康复策略。此外,决定结果表现的一系列因素表明,有必要采用个性化康复方法来治疗个别 CI 患者。
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引用次数: 0
Interaction between deglutition, tongue posture, and malocclusion: A comparison of intraoral compartment formation in subjects with neutral occlusion or different types of malocclusion. 脱舌、舌位和错合畸形之间的相互作用:比较中性咬合或不同类型错颌畸形受试者口内隔间的形成。
Pub Date : 2016-09-01 Epub Date: 2016-02-19 DOI: 10.2319/101615-699.1
Michael Knösel, Carolin Nüser, Klaus Jung, Hans-Joachim Helms, Wilfried Engelke, Paulo Sandoval

Objective: To test the null hypothesis of no significant difference in terms of intraoral pressure curve characteristics assessed simultaneously at the subpalatal space (SPS) and the vestibular space (VS), during different oral postures, between four groups with either an Angle Class II/1 (II1), Angle Class II/2 (II2), anterior open bite (O) malocclusion, or a neutral occlusion control group (I).

Materials and methods: Intraoral pressure recordings were performed simultaneously in the VS and SPS of 69 consecutive subjects (nII1  =  15; nII2  =  17; nO  =  17; nI  =  20; mean age/standard deviation 18.43/6.60 years). Assessments included defined sections of open mouth posture (OMP, 30 seconds), anteriorly closed mouth condition (60 seconds), dynamics by a tongue-repositioning maneuver (TRM, 60 seconds), swallowing, and positive pressure generation (PP, 10 seconds). Interactions of malocclusion, compartment location, and posture on pressure curve characteristics were analyzed by Kruskal-Wallis and Mann-Whitney U-tests, adopting an α level of 5%.

Results: Globally significant group differences were detected at the VS (plateau duration and median peak heights during TRM; area under pressure curve [AUC] during PP) and SPS (AUC during TRM and PP). Subjects with anteriorly nonopen dental configurations (groups I and II2) were able to keep negative pressure levels at the VS for longer time periods during TRM, compared to groups O and II1.

Conclusions: The null hypothesis was rejected for mean VS plateau durations and peak heights and for SPS AUC. Negative pressures at the VS may stabilize outer soft tissues passively and may explain the dental arch form shaping effect by mimic muscles.

目的在不同口腔姿势下,同时在腭下间隙(SPS)和前庭间隙(VS)评估口内压力曲线特征,以检验四组咬合角度II/1级(II1)、咬合角度II/2级(II2)、前开放咬合(O)错颌畸形或中性咬合对照组(I)之间是否存在显著差异的零假设:对 69 名连续受试者(nII1 = 15;nII2 = 17;nO = 17;nI = 20;平均年龄/标准偏差为 18.43/6.60 岁)的 VS 和 SPS 同时进行口内压力记录。评估包括定义的张口姿势(OMP,30 秒)、前闭口状态(60 秒)、舌头复位动作(TRM,60 秒)、吞咽和正压产生(PP,10 秒)等部分。通过 Kruskal-Wallis 和 Mann-Whitney U 检验分析了错牙合畸形、隔间位置和姿势对压力曲线特征的交互作用,采用的α水平为 5%:结果:在 VS(TRM 时的高原持续时间和中位峰高;PP 时的压力曲线下面积 [AUC])和 SPS(TRM 和 PP 时的压力曲线下面积)上发现了明显的组间差异。与 O 组和 II1 组相比,前牙不开放的受试者(I 组和 II2 组)在 TRM 期间能够在 VS 处保持较长时间的负压水平:就 VS 平均高原持续时间和峰值高度以及 SPS AUC 而言,零假设被否定。VS负压可被动地稳定外部软组织,并可解释模拟肌肉对牙弓形态的塑造作用。
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引用次数: 0
The Endocannabinoid System as a Therapeutic Target in Glaucoma. 作为青光眼治疗靶点的内源性大麻素系统。
IF 3.1 Pub Date : 2016-01-01 Epub Date: 2016-01-12 DOI: 10.1155/2016/9364091
Elizabeth A Cairns, William H Baldridge, Melanie E M Kelly

Glaucoma is an irreversible blinding eye disease which produces progressive retinal ganglion cell (RGC) loss. Intraocular pressure (IOP) is currently the only modifiable risk factor, and lowering IOP results in reduced risk of progression of the disorder. The endocannabinoid system (ECS) has attracted considerable attention as a potential target for the treatment of glaucoma, largely due to the observed IOP lowering effects seen after administration of exogenous cannabinoids. However, recent evidence has suggested that modulation of the ECS may also be neuroprotective. This paper will review the use of cannabinoids in glaucoma, presenting pertinent information regarding the pathophysiology of glaucoma and how alterations in cannabinoid signalling may contribute to glaucoma pathology. Additionally, the mechanisms and potential for the use of cannabinoids and other novel agents that target the endocannabinoid system in the treatment of glaucoma will be discussed.

青光眼是一种不可逆的致盲性眼病,会导致视网膜神经节细胞(RGC)逐渐丧失。眼压(IOP)是目前唯一可改变的风险因素,降低眼压可减少疾病恶化的风险。内源性大麻素系统(ECS)作为治疗青光眼的潜在靶点引起了广泛关注,这主要是由于在服用外源性大麻素后观察到了降低眼压的效果。不过,最近有证据表明,调节 ECS 也可能具有神经保护作用。本文将回顾大麻素在青光眼中的应用,介绍有关青光眼病理生理学的相关信息,以及大麻素信号的改变如何可能导致青光眼病理。此外,还将讨论针对内源性大麻素系统的大麻素和其他新型制剂用于治疗青光眼的机制和潜力。
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引用次数: 0
Transfer of soy isoflavone into the egg yolk of chickens. 将大豆异黄酮转移到鸡的蛋黄中。
IF 1.6 Pub Date : 2001-10-01 DOI: 10.1271/bbb.65.2220
S Saitoh, T Sato, H Harada, T Takita

A diet containing a high concentration of soy isoflavone was administered to laying hens and the contents of the isoflavones transferred to the plasma and egg yolk were measured. A method for quantitatively measuring the concentration of isoflavone in the yolk was first established, before a high concentration of soy isoflavone was administered to the laying hens over an 18-day period. The concentrations of isoflavone in the plasma and egg yolk reached their highest on the 12th day of the feeding period, the values being 3,167 nmol/l and 65.29 microg/100 g, respectively. The concentration of cholesterol in the yolk was slightly affected during the early stages of the feeding period. These findings clearly demonstrate that soy isoflavone was transferred into the yolk from the feed and that the cholesterol concentration in the yolk was affected by administering the soy isoflavone-enriched feed.

给蛋鸡饲喂含有高浓度大豆异黄酮的饲料,并测量转移到血浆和蛋黄中的异黄酮含量。首先建立了定量测量蛋黄中异黄酮浓度的方法,然后在 18 天内给蛋鸡饲喂高浓度大豆异黄酮。血浆和蛋黄中的异黄酮浓度在饲喂期的第 12 天达到最高值,分别为 3,167 毫摩尔/升和 65.29 微克/100 克。蛋黄中的胆固醇浓度在饲喂初期受到轻微影响。这些研究结果清楚地表明,大豆异黄酮从饲料中转移到了蛋黄中,并且蛋黄中的胆固醇浓度受到了富含大豆异黄酮饲料的影响。
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引用次数: 42
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