需行全身照射患者辐射损伤血浆代谢谱的研究

目的利用代谢组学的方法发现与人辐射损伤密切相关的特征血浆代谢物,初步探讨辐射损伤涉及的代谢通路。方法收集2012年1月至2014年5月期间40名患者全身照射（TBI）辐照前后的血浆样本,通过气相色谱-质谱（GC-MS）联用的代谢组学方法研究TBI对人血浆代谢物的影响,并筛选出与TBI损伤密切相关的特征血浆代谢物。结果 TBI后,血浆中葡萄糖、肉豆蔻酸、草酸、3-羟基丁酸、尿素、天冬氨酸、缬氨酸、亮氨酸、赖氨酸和苏氨酸含量显著增加（P<0.05）,胆固醇、丙酮酸、丙酸、乳酸、丙氨酸、甘氨酸、肌醇、山梨糖酐、乙二醇和次黄嘌呤含量显著降低（P<0.05）。结论 TBI可引起人体血浆中代谢物水平显著变化,主要涉及氨基酸代谢、糖代谢、脂代谢等代谢通路。     

全胸照射引起的大鼠血浆辐射损伤早期代谢特征研究

目的 探索大鼠全胸照射（WTI）后早期血浆代谢特征的变化,为寻找非均匀局部照射辐射损伤生物标志物以及揭示辐射损伤机制提供实验依据。方法 雄性Wistar大鼠按完全随机分组法分为健康对照组和WTI照射组。气相色谱-质谱联用（GC-MS）技术考察大鼠WTI后第2、3、5天血浆代谢物水平的动态变化,筛选出辐射损伤特征差异代谢物,并对其涉及的代谢通路进行探讨。结果 主成分分析（PCA）显示健康对照组和WTI照射组的代谢差异随照后时间的延长愈加明显。与健康对照组相比,WTI后3~5 d,丙氨酸、棕榈酸、硬脂酸、乳酸、葡萄糖等代谢物在血浆中显著性上升（F=13.51、5.20、9.87、10.59、7.05,P<0.05）,蛋氨酸、缬氨酸、苏氨酸、富马酸、苹果酸、α-酮戊二酸、磷酸、赖氨酸等显著性下降（F=15.68、5.63、3.78、12.83、2.88、8.93、4.68、6.43,P<0.05）。结论 WTI照射可引起血浆代谢轮廓改变,差异代谢物主要涉及氨基酸代谢、三羧酸（TCA）循环、脂类代谢等代谢途径。     

大鼠血浆辐射敏感脂质代谢物的筛选

目的 筛选大鼠血浆辐射敏感脂质代谢物并探索其代谢通路,为辐射损伤生物标志物研究提供科学依据。方法 用⁶⁰Co γ射线对大鼠进行全身照射,照射剂量分别为0、1、3、5 Gy,采用基于液相色谱质谱串联平台的非靶向脂质组学方法,检测大鼠受照后血浆中脂质代谢物的变化。结果 大鼠受照后7 d,血浆中共有20个脂质代谢物相对含量发生显著变化,其中13个明显上调,7个明显下调。12个脂质代谢物具有良好的剂量-效应关系。结论 大鼠受到γ射线照射后,血浆中脂质代谢物水平发生显著变化,主要涉及鞘脂代谢、甘油磷脂代谢、糖基磷脂酰肌醇代谢等代谢通路。     

功能代谢组学在生物医药领域中的应用

功能代谢组学是代谢组学的延伸,即通过检测生物体受到特定刺激与干扰后内源性代谢物的变化,获取生物代谢标志物并进一步采用实验方法验证代谢标志物及其关联的酶、基因与蛋白等的功能,可从“代谢物-酶-基因-蛋白”角度系统揭示病理生理改变的分子机制,阐明代谢物关联的上下游生物机制。本文对目前功能代谢组学在生物医药领域中的常用方法和研究策略、疾病靶点及发病机制探索、药物作用机制分析等进行综述,同时对功能代谢组学与网络药理学、重编程代谢组学相结合的延伸研究进行总结,最后分析并展望功能代谢组学在生物医药领域的应用前景。     

超高剂量率照射与常规照射后胶质瘤小鼠血浆代谢物时序性特征对比分析

目的探究超高剂量率照射(FLASH-RT)和常规照射(CONV-RT)对胶质瘤小鼠血浆代谢物的影响。方法胶质瘤模型雄性C57BL/6J小鼠21只, 按随机数表法分成健康对照组(3只)、CONV-RT组(9只)和FLASH-RT组(9只)。CONV-RT组以0.4 Gy/s的剂量率对小鼠头部进行单次24 Gy照射, FLASH-RT组以60 Gy/s的剂量率对小鼠头部进行单次24 Gy照射, 健康对照组以相同条件给予0 Gy假照射。两照射组照射后1、3、7 d分别收集小鼠眼内眦静脉血并分离血浆。健康对照组于假照射后7 d收集小鼠眼内眦静脉血并分离血浆。采取基于液相色谱质谱串联平台的非靶向代谢组学方法检测胶质瘤小鼠血浆代谢物的变化。结果胶质瘤小鼠受不同方式照射后, 血浆中代谢物均发生显著变化。FLASH-RT组和CONV-RT组3个时间点分别与健康对照组相比筛选出12和5种差异代谢物, 照后1 d血浆代谢物差异最大, 照后3和7 d血浆代谢物差异减小。FLASH-RT组筛选出的花生四烯酸与异戊酸也存在于CONV-RT组中, 其余10种差异代谢物仅存在FLASH-RT组, 主要涉及能量代谢和...     

基于UPLC-Q/TOF-MS/MS法的异鼠李素在小鼠体内代谢产物研究

目的 采用超高效液相色谱-四极杆-飞行时间串联质谱（UPLC-Q/TOF-MS/MS）技术,分析小鼠灌胃给予异鼠李素后的体内代谢产物。方法 将12只C57BL/6J小鼠随机分为给药组和空白组,给药组按100 mg/（kg·d）剂量灌胃给予异鼠李素的0.5%羧甲基纤维素钠混悬液,空白组给予相应体积的0.5%羧甲基纤维素钠溶液,分别收集小鼠粪便、尿液、血液和胆汁。采用不同的C18柱进行分离,柱温及自动进样器的温度分别为30和4℃,流动相为0.1%甲酸水溶液（A）-乙腈（B）。采用ESI（-）模式,扫描范围m/z 50～1700。结果 经灌胃给药后,在小鼠体内共鉴定出1种原形成分和25种代谢产物,分别分布于粪便（19种）、尿液（15种）、血液（5种）和胆汁（2种）。结论 异鼠李素在小鼠体内可分别发生羟基化、去羟基化、糖化、脱糖化、硫酸化、甲基化、乙酰化、氢化和葡萄糖醛酸化的代谢反应,这些代谢产物可能是异鼠李素发挥药效的潜在物质基础。     

基于血清代谢组学探究摔跤运动员比赛前后代谢变化特征

目的：用超高效液相色谱-四级杆串联飞行时间质谱法（UPLC-Q-TOF-MS）研究摔跤运动员比赛前后血清代谢变化特征，为科学化营养补充实现快速恢复以及发现训练监控新指标提供新思路。方法：筛选女子摔跤运动员11人（年龄22.09±2.77岁，身高1.63±0.04 m，体重60.45±8.43 kg，运动等级为一级运动员或运动健将），分别于比赛前1天、比赛结束归队后次日清晨7时空腹进行肘静脉采血，共计采血2次。每次各采集肘静脉血两管，一管（3 mL）用于全血生化指标分析，另一管（5 mL）离心后取血清用于生化指标检测和代谢组学检测。采用UPLC-Q-TOF-MS进行代谢组学检测及数据分析，确定运动前后的代谢差异物，获取的差异代谢物进行通路分析，确定比赛前后涉及的潜在代谢通路变化。同时对检测的生化指标与代谢物进行皮尔森相关性分析。结果：（1）运动员赛后血清尿素（BU）、血清总睾酮（TT）水平显著高于赛前（P<0.01,P<0.05），红细胞压积（HCT）显著低于赛前（P<0.05）。（2）根据组间比较的P值小于0.05和正交偏最小二乘分析的变量重要性（variable i...     

HPLC-MS/MS测定比格犬血浆中非诺贝酸浓度及其药代动力学研究

目的建立快速有效的HPLC-MS/MS方法测定比格犬血浆中非诺贝特的代谢物非诺贝酸,并探讨其在比格犬体内的药代动力学。方法 4只健康雄性比格犬随机分为两组,在禁食状态下口服给药〔非诺贝特片（纳米）和对照药Tri-cor〕,HPLC-MS/MS测定非诺贝酸浓度。流动相为甲醇-水（0.1%甲酸）,在200μl.min-1流速下梯度洗脱,地西泮为内标,色谱柱为Thermo Syncronic-C8,柱温：20℃。质谱测定利用多离子监测扫描模式,电离方式为ESI正离子模式,检测离子反应非诺贝酸为m/z 319.10→232.86,地西泮为m/z 285.04→193.04。血药浓度数据经Origin Pro 7.5与WinNonlin Phoenix软件处理,计算主要药动学参数。结果本方法中非诺贝酸在5～1000 ng.ml-1范围内线性良好（r2〉0.98）,定量下限为5 ng.ml-1。方法的精密度准确度,专属性,绝对回收率,稳定性和基质效应均符合要求。非诺贝特纳米片和Tricor在比格犬体内的主要药动学参数：tmax为（1.50±1.16）和（1.94±2.48）h、t1/2为（8.58±3.41）和（8.02±2.08）h、Cmax为（5857.20±3563.44）和（6697.56±3912.92）ng.ml-1、AUC为（25 328.13±16 009.09）和（26 379.89±17 392.47）ng.h.ml-1。结论建立了准确、灵敏的HPLC-MS/MS检测方法用于比格犬血浆中非诺贝特代谢产物非诺贝酸的含量测定;研究了非诺贝酸在比格犬体内的药代动力学,结果显示非诺贝酸在比格犬体内的代谢动力学过程呈单室模型,该结果为不同来源非诺贝特片的生物等效性研究奠定了基础,为非诺贝特临床安全合理用药提供参考依据。     

芥子气中毒体内诊断生物标志物检测技术的研究进展

芥子气中毒体内诊断生物标志物检测技术的研究一直是人们关注的课题，目前芥子气中毒的生物诊断标志物主要有芥子气-DNA加合物、芥子气-蛋白质加合物及芥子气的尿中代谢物(包括水解产物及谷胱甘肽结合物)等。本文综述了上述3类生物诊断标志物的检测方法，包括液质联用(LC-MS)、气质联用(GC-MS)、免疫荧光等技术。     

慢性胃炎和胃癌患者血浆、单个核细胞中cAMP、cGMP水平测定及其临床意义

本文采用放免分析法测定了正常人、慢性胃炎和胃癌患者血浆和单个核细胞内cAMP和cGMP水平,发现胃癌(GC)和慢性萎缩性胃炎(CAG)患者血浆cAMP和cGMP水平分别下降和升高,二者比值下降,单个核细胞cAMP下降。提示GC和CAG患者体内环核苷酸代谢异常,并在环核苷酸代谢上有一定的联系;cAMP/cGMP比值有助于GC的诊断。     

功能性消化不良患者的胆囊排空功能评价

目的探讨胆囊排空功能及胃肠激素水平变化在功能性消化不良(FD)发病机制中的作用.方法采用放射免疫分析法(RIA)和放射性核素显像法测定32例FD患者、20例健康志愿者空腹及脂餐后60min血浆胃动素(MTL)、胆囊收缩素(CCK)、血管活性肠肽(VIP)、生长抑素(SS)及胆囊排空功能,获得不同时相胆囊排空指数.结果FD组空腹及餐后胆囊排空指数、MTL均低于对照组,差异均有显著性(P均<0.001),且MTL与胆囊排空指数呈正相关(r空腹=0.82,r餐后=0.94,P均<0.01);FD组空腹血浆CCK与对照组比较差异无显著性(P>0.05),餐后低于对照组,差异有显著性(P<0.001),且餐后CCK与胆囊排空指数呈显著正相关(r=0.97,P<0.01);FD组空腹与餐后血浆VIP均高于对照组,差异有显著性(P<0.001),VIP与胆囊排空指数呈负相关(r空腹=-0.81,r餐后=-0.47,P均<0.01).FD组空腹及餐后血浆SS与对照组相比差异无显著性.结论FD患者(运动障碍型)存在空腹及餐后胆囊排空障碍.血浆促胃肠动力激素(MTL、CCK)水平下降和抑制胃肠动力激素(VIP)水平升高是FD患者胆囊排空障碍的病因和重要的病理生理基础.     

Adenosine-induced long-standing postischemic left ventricular dysfunction evaluated with gated SPECT

OBJECTIVES: This study was performed to determine the after-effects of pharmacologic stress (adenosine) on left ventricular (LV) function-end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (LVEF)-with Tl-201 and Tc-99m MIBI SPECT. METHODS: A total of 263 patients were grouped according to the time interval between isotope injection and imaging. Group A: within 1 hour (n = 99; men, n = 48; women, n = 51; mean age: 63.2 years), subgrouped as patients with no perfusion defect (NPD; n = 61), reversible defect (RD; n = 33), and fixed defect (FD; n = 5). Group B: 1 to 2 hours (n = 110; men, n = 66; woman, n = 44; mean age, 63 years), NPD (n = 64), RD (n = 26), and FD (n = 20). 3) Group C: 2 to 3 hours (n = 54; men, n = 30; women, n = 24; mean age, 62 years); NPD (n = 22), RD (n = 17), and FD (n = 15). All patients were in sinus rhythm during the study and had no prior history of myocardial infarction. RESULTS: In group A, in the patients with RD, poststress LVEF was significantly depressed after adenosine infusion (53.1 +/- 9.5% vs 58.3 +/- 10.2%, P < 0.001) and showed a wall motion abnormality, which was worse after stress than during rest. The mean difference in LVEF (DeltaLVEF) between rest and stress was 5.2%. The DeltaLVEF in those patients with RD was significantly higher than that in the NPD (0.9%, P < 0.01) or FD (2.1%, P < 0.05) subgroups. Twenty of the 33 patients (60.6%) with RD showed an increase in LVEF > or = 5% from poststress to rest, and the poststress ESV (43.3 +/- 19.0 mL) was significantly higher than the ESV (38.5 +/- 18.4 mL, P < 0.01) at rest, but there was no significant difference in the EDV (90.5 +/- 26.4 vs 89.7 +/- 26.2 mL). In group B, DeltaLVEF was 1.5%, 4.4%, and 1.2% in patients with NPD, RD, and FD respectively. In group C, DeltaLVEF was 2.5%, 3.2%, and 0.9% in patients with NPD, RD, and FD respectively, and there was no significant difference in DeltaLVEF among patients. In group C, 4 of 17 patients (23.5%) with RD showed an increase in LVEF > or = 5% from poststress to rest. CONCLUSION: These results showed that adenosine stress-induced postischemic LV dysfunction is well noted on early quantitative gated SPECT in patients with RD and can also be observed on delayed gated SPECT, even though the incidence of LV dysfunction is less than that in early gated SPECT.     

功能性消化不良患者血浆胃肠激素水平的变化

 目的探讨胃肠激素在功能性消化不良(Ftmctional dyspepsia,FD)疾病过程的可能作用和临床意义.方法应用放射免疫分析法检测FD组28例及正常组26例血浆中胃动素(MTL)、胆囊收缩素(CCK)、胃泌素(Gas)、生长抑素(SS)和血管活性肠肽(VIP)水平.结果FD组血浆MTL水平明显低于正常组(P＜0.01);FD组血浆Gas及SS值明显高于正常组(P＜0.05);而FD组血浆CCK和VIP值与正常组相比,差异无显著性(P＞0.05).结论血浆中MTL、Gas及SS水平的变化可能是FD胃肠运动功能障碍的原因;而CCK和VIP在FD的发病机制中无重要作用.     

Measurement of effective renal plasma flow: a comparison of methods

We have compared two in vitro methods and three variations of kidney background (BG) subtraction within a gamma camera method (41 examinations, 31 patients) for determination of effective renal plasma flow (ERPF) using 131I orthoiodohippurate (OIH). Method I: plasma samples at 20 and 45 min after OIH injection, ERPF = dose X slope/intercept; Method II: 45-min plasma sample, ERPF = -51.1 + 8.21x + 0.019x2, x = dose/45-min plasma activity/I. Individual kidney and total ERPF were determined from gamma camera (GC) methods using renal uptake 1-2 min after injection. All methods were compared against Method I (previously validated against paraaminohippurate (PAH) clearances). Method II, which requires one blood sample is more accurate than GC methods. GC methods are insensitive to operator variability in placement of renal and BG regions of interest. They may be useful to follow changes in relative or total ERPF, but accurate depth correction of renal data is suggested. In vitro, blood sample-based methods are more accurate.     

黛力新治疗功能性消化不良临床分析

目的比较黛力新联合雷贝拉唑、贝络纳与雷贝拉唑,贝络纳治疗功能性消化不良近期疗效及半年复发情况。方法将90例经内镜等检查诊断为功能性消化不良的门诊患者,随机分为:治疗组50例和对照组40例,治疗组采用黛力新联合雷贝拉唑、贝络纳治疗;对照组采用雷贝拉唑、贝络纳治疗。结果治疗组及对照组治疗8周后症状改善,餐后饱胀不适及早饱、反复上腹疼痛,上腹烧灼总有效率及症状积分有效率分别为94.0%,83·3%,96.4%,88.5%和85.0%;73.5%,86.9%,81.5%。半年复发率分别为14.0%及25.0%,二组比较有效率差异显著(P<0.05)。结论黛力新与雷贝拉唑对功能性消化不良的近期及维持治疗均有良好疗效,无明显不良反应,但停药后复发率较高,需要维持治疗。     

胃肠激素与功能性消化不良患者胃肠动力障碍的关系

目的　探讨胃肠激素与功能性消化不良 (FD)患者胃肠动力障碍的关系。方法　对 5 4例FD患者进行胃排空检查 ,根据结果将其分为胃排空延缓FD组和胃排空正常FD组 ,另以 17例正常人作为对照组。用放免法测定受试者空腹和餐后血浆NT、MTL、Gas、SS含量。结果　胃排空延缓FD组空腹和餐后血浆NT含量、餐后血浆Gas含量明显高于正常人及胃排空正常FD组 ,空腹和餐后血浆MTL含量则明显低于另外两组 ,而空腹和餐后血浆SS与另外两组比较差异无统计学意义。结论　FD患者胃肠动力障碍与NT、MTL、Gas密切相关 ;NT、MTL、Gas在FD的发病机制中可能有一定作用。     

新训战士功能性消化不良治疗前后胃肠激素水平变化的研究

 目的探讨武警新训战士中功能性消化不良(Functional dyspepsia,FD)患者应用多潘立酮、马来酸曲美布汀及安慰剂的治疗效果及其胃动素(MTL)、胆囊收缩素(CCK)的变化水平,探索特殊人群中FD的发病特点和不同治疗方案的效果.方法确诊为FD的新兵随机分为多潘立酮组,马来酸曲美布汀组和安慰剂组,治疗前填写FD症状自评量表、检测血浆MTL、CCK水平,治疗2周后复查血浆MTL、CCK水平并填写FD症状自评量表.结果三组患者FD评分治疗后明显低于治疗前(P＜0.01),三组患者血浆MTL水平低于正常人群,CCK水平高于正常人群;各组治疗后血浆MTL水平明显上升(P＜0.05),治疗后血浆CCK水平仅马来酸曲美布汀组较治疗前明显下降(P＜0.01).结论促动力药治疗特殊人群FD的效果可靠,同时安慰剂治疗也可取得较好的疗效;FD的发生和MTL、CCK水平变化相关.     

Castleman disease of the abdomen: imaging spectrum and clinicopathologic correlations

PURPOSE: The purpose of this work was to define the imaging spectrum of Castleman disease of the abdomen and to correlate the results with clinicopathologic findings. METHOD: Seventeen patients (male/female 7:10; mean age 35.6 years) with pathologically proved Castleman disease in the abdomen were included in this study. Radiologic findings (CT, n =17; US, n =10; MR, n =1) were retrospectively reviewed by two readers and were correlated with clinical and pathologic findings. RESULTS: Subjects were divided into those with localized (n = 11) and disseminated (n = 6) disease. In localized disease, the pathologic subtypes were hyaline vascular type in eight and plasma cell type in three. Radiologic studies showed a single large mass in six and a single dominant mass with small satellite nodules in five. Central low attenuation was seen in two cases, and calcification was seen in three cases. Regional lymphadenopathy was found in five cases. In disseminated disease, there were three hyaline vascular types and three plasma cell types. Radiologic findings included diffuse lymphadenopathy (n = 6), hepatosplenomegaly (n = 5), ascites (n = 3), and thickening of the retroperitoneal fascia (n = 3). Disseminated disease revealed symptoms and abnormal laboratory findings (anemia, hypoalbuminemia, elevated erythrocyte sedimentation rate/C-reactive protein, etc.) more frequently than localized disease and showed poor prognosis. CONCLUSION: There are two distinctive types of radiologic manifestations in Castleman disease of the abdomen: localized and disseminated. The localized type usually shows single or multiple discrete masses, and the disseminated type frequently shows nonspecific organomegaly and lymphadenopathy.     

星状神经节阻滞对大鼠严重创伤后垂体-甲状腺、肾上腺皮质轴的影响

目的 观察大鼠严重创伤后垂体-甲状腺、肾上腺皮质轴变化及星状神经节阻滞(SGB)的影响.方法 建立大鼠严重创伤(右侧胸部撞击伤复合同侧股骨闭合性骨折)模型,动物分3组:正常对照组(n=12);创伤治疗组(n=12),创伤后即刻、8小时以0.125%布比卡因0.3ml行SGB;创伤对照组(n=12),于同一部位给予0.3ml生理盐水.于创伤后24小时取动脉血,测定血浆促肾上腺皮质激素(ACTH)、皮质醇(GC)、促甲状腺激素(TSH)、三碘甲状腺原氨酸(T3)、甲状腺素(T4)水平.结果 创伤后血浆T3、T4水平较正常对照组降低(P<0.05),但TSH变化不显著,行SGB后TSH、T3、T4尽管数值上增加,但变化不明显;创伤后血浆ACTH、GC水平较正常对照组升高(P<0.01、P<0.05),行SGB后ACTH、GC水平降低(P<0.01、P<0.05).结论 严重创伤后垂体.甲状腺、肾上腺皮质轴发生明显变化,SGB能减轻其变化.     

C-reactive protein serum concentrations in well-trained athletes

Previously it had been shown that there is a sharp increase in C-reactive protein (CRP) serum concentration during the first few days after severe exercise. To evaluate the effect of physical training on the CRP levels, a sensitive enzyme immunoassay was developed and used to assess the basal CRP concentrations in 356 male and 103 female athletes, who trained at least 4 times per week in various disciplines, in 45 male and 40 female untrained controls, and in 35 elderly coronary patients. In male athletes the lowest CRP values were found in swimmers (median: 102 ng/ml, n = 59), which were significantly lower (P less than 0.001) than those of male controls (median: 502 ng/ml, n = 45). The CRP concentrations in rowers (median: 260 ng/ml, n = 108) were also significantly lower (P less than 0.01) than in the control group. CRP levels in middle- and long-distance runners (median: 315 ng/ml, n = 53), racing cyclists (median: 620 ng/ml, n = 111), and soccer players (median: 660 ng/ml, n = 25) did not differ significantly from those of the controls. In female athletes the lowest CRP concentrations were also found in swimmers (median: 110 ng/ml, n = 49), which were significantly lower (P less than 0.001) than those of the female controls (median: 396 ng/ml, n = 40). Female middle- and long-distance runners (n = 36) and female rowers (n = 18) had median CRP values of 250 and 285 ng/ml, respectively. This results suggest that training induces a suppressive effect upon CRP, responsible for the low serum levels in athletes (particularly swimmers) when compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)