Study on the Hook Effect in the Detection of Beta2-Microglobulin with Different Reagents in Fully Automated Biochemical Analyzers

Objective:To investigate the hook effect in the detection of beta2-microglobulin(β2-MG)with different reagents as well as on two fully automated biochemical analyzers and their solutions.Methods:Using immunoturbidimetric assay forβ2-MG as the research object,β2-MG levels were detected by different concentration gradients ofβ2-microglobulin samples in Liedemann,Mack,and Myriad reagents of three manufacturers on two automatic biochemical analyzers,and the difference of the hook effect was comparatively analyzed.Results:Leadman reagent showed the hook effect on the Beckman AU5800 automated biochemistry analyzer,while both Maccura and Mindray reagents did not show the hook effect.After the experiments,we found the limit value of the pre-zone check of Leadman reagent,and changed the parameters of the instrument,when the limit value of the pre-zone check was reached,the instrument automatically diluted the specimen five times and then detected it again.After changing the parameters of the instrument,the correlation between the three methods of detecting samples of different concentrations was r>0.99.Conclusion:Before selecting the application of immunoturbidimetric reagents,we have to carry out the risk assessment of the hook effect and selectively set the parameters of the pre-zone check based on the highest concentration that may occur in the clinic;for the items that may have the hook effect,we have to selectively set the parameters of the pre-zone check when the ratio of average reaction rate and the immediate reaction rate is at the limit value,and the phenomenon of antigen excess may occur,the instrument will carry out automatic dilution before detection,so as to avoid the issuance of erroneous results of high-value samples due to the hook effect.

尿微量白蛋白与尿肌酐比值、尿视黄醇结合蛋白及尿β2微球蛋白联合检测对糖尿病肾病的诊断价值

目的 探讨尿微量白蛋白与尿肌酐比值(ACR)、尿视黄醇结合蛋白(RBP)及尿β2微球蛋白(β2-MG)联合检测对糖尿病肾病的诊断价值。方法 对2022年1月—2023年6月本院收治的2型糖尿病(T2DM)患者200例临床资料进行回顾性分析,根据是否有糖尿病肾病分为肾病组(100例)、单纯糖尿病(DM)组(100例),均接受ACR、RBP及β2-MG联合检测,对检测结果进行分析。结果 肾病组ACR、RBP、β2-MG水平与单纯糖尿病组比较有明显差异(P<0.05);肾病组患者不同Mogensen分期患者的尿微量白蛋白/尿肌酐比值、尿视黄醇及尿β2微球蛋白水平比较有明显差异(P<0.05);单项检测的诊断特异度、灵敏度明显较联合检测低(P<0.05)。结论 ACR、RBP、β2-MG联合检测对糖尿病肾病具有较高的检测价值,在出现早期肾损伤时即可检出,也有助于评估肾病程度,为临床制定治疗方案提供参考依据。

Lrrk2 R1628P转基因小鼠尿液外泌体诱导帕金森病样病理变化

目的:探讨Lrrk2 R1628P转基因小鼠尿液外泌体能否诱导帕金森病(PD)样病理改变。方法:提取野生型(WT)和Lrrk2 R1628P转基因小鼠尿液外泌体,使用免疫印迹法检测尿液外泌体标记物TSG101和CD81,Y216位点磷酸化糖原合成酶激酶-3β(pGSK-3β-216)表达水平。在C57小鼠纹状体中分别注射WT小鼠(C57-WT组,n=8)和Lrrk2 R1628P小鼠尿液外泌体(C57-Lrrk2组,n=8)。注射前3天,注射后1、3、6个月,利用平衡木、挂线、转棒和旷场实验对小鼠进行行为学分析,免疫组化法分析脑组织中磷酸化α-突触核蛋白(pα-syn)的沉积情况,免疫印迹法检测脑组织中pα-syn的表达。结果:Lrrk2 R1628P小鼠尿液外泌体TSG101和CD81表达水平与WT小鼠比较,差异无统计学意义(P>0.05),pGSK-3β-216表达水平高于WT小鼠(P<0.001)。C57-Lrrk2组小鼠出现PD样行为学表型(P<0.001),皮层、纹状体和黑质中有pα-syn沉积,脑组织中pα-syn表达水平为(0.44±0.06),C57-WT组则无表达(P<0.001)。结论:小鼠纹状体中注射Lrrk2 R1628P转基因小鼠的尿液外泌体能够诱导PD样病理改变。

吉林省某医院成年人尿中邻苯二甲酸二(2-乙基己基)酯的暴露水平及其影响因素

目的评估成年人尿中邻苯二甲酸二(2-乙基己基)酯[di(2-ethylhexyl)phthalate,DEHP]代谢物水平及其影响因素。方法2022年3月本研究纳入吉林省某医院210名成年人,采集晨尿样并通过高效液相色谱串联质谱法测定尿液中5种DEHP代谢物(MEHP、MEOHP、MEHHP、MCMHP和MECPP)的水平。通过Spearman秩相关分析研究对象尿液中DEHP代谢产物浓度之间的关系,采用独立样本t检验比较每种变量不同项目间DEHP代谢产物水平的差异,使用多元线性回归模型分析所选因素与研究对象尿液中DEHP代谢产物水平之间的关系。结果MEHP和MEOHP检出率分别为98.6%和99.5%,MEHHP、MCMHP和MECPP的检出率均为100.0%。MCMHP的中位数浓度最高,为14.45μg/L(14.10μg/g肌酐)。在调整协变量后,主动吸烟与尿液MEOHP(β=-0.151,95%CI:-0.299~-0.004)显著相关;被动吸烟与MCMHP(β=-0.184,95%CI:-0.323~-0.045)、MECPP(β=-0.192,95%CI:-0.332~-0.051)和∑DEHP(β=-0.146,95%CI:-0.291~-0.001)显著相关;塑料水杯的使用与MEHHP(β=-0.147,95%CI:-0.284~-0.009)显著相关;护肤类化妆品的使用频率与MEOHP(β=-0.115,95%CI:-0.297~-0.012)和MEHHP(β=-0.194,95%CI:-0.337~-0.051)显著相关。结论本研究中成年人广泛暴露于DEHP,日常生活中不吸烟及远离二手烟、减少塑料水杯和护肤类化妆品的使用可降低DEHP的暴露水平。

Urine Metabonomic Analysis of Interventions Effect of Soy Isoflavones on Rats Exposed to Di-(2-ethylhexyl) Phthalate

Objective Di-(2-ethylhexyl) phthalate(DEHP) is a ubiquitous environmental contaminant.As an endocrine disruptor,it seriously threatens human health and ecological environmental safety.This study examines the impact of intervention with soybean isoflavones(SIF) on DEHP-induced toxicity using a metabonomics approach.Methods Rats were randomly divided into control(H),SIF-treated(A,86 mg/kg body weight),DEHP-treated(B,68 mg/kg),and SIF plus DEHP-treated(D) groups.Rats were given SIF and DEHP daily through diet and gavage,respectively.After 30 d of treatment,rat urine was tested using UPLC/MS with multivariate analysis.Metabolic changes were also evaluated using biochemical assays.Results Metabolomics analyses revealed that p-cresol glucuronide,methyl hippuric acid,N1-methyl-2-pyridone-5-carboxamide,lysophosphatidycholine [18:2(9 Z,12 Z)] {lyso PC [18:2(9 Z,12 Z)]},lyso PC(16:0),xanthosine,undecanedioic acid,and N6-acetyl-l-lysine were present at significantly different levels in control and treatment groups.Conclusion SIF supplementation partially protects rats from DEHP-induced metabolic abnormalities by regulating fatty acid metabolism,antioxidant defense system,amino acid metabolism,and is also involved in the protection of mitochondria.

Improvement of resolution in 2-D gel analysis by simple pre-treatment of human urine with EDTA

Regardless of thermodynamic stability, less complex proteome than plasma, convenient and noninvasive sampling of urine, reproducibility and comparability of the data among laboratories are challenges for the urine proteome analysis. Pretreatment of urine with 10 mM EDTA in conjunction with desalting methods to remove interfering molecules significantly improved the presentation of urine proteome on 2-D gels. Statistical analysis of the average ratio of the spot numbers on 2-D gels between EDTA-treated and non-treated samples were 1.35 ± 0.167, 1.26 ± 0.091, and 1.24 ± 0.095 for dialysis, ultrafiltration, and desalting column, respectively, with the p-value of 5.85 × 10–6 for the overall comparison. This result came from the fact that EDTA-treated samples showed better resolutions with less streaks and clearer spots on 2-D gels than the control samples. The results suggest that a simple and non-fractionating EDTA-treatment can be employed to the procedures for the high resolution 2-D gel analysis and other urinary proteomic analysis.

Changes of serum β2-MG, Cys C and urine mAlb levels in patients with ureteral calculi before and after extracorporeal shock wave lithotripsy and their clinical significance

Objective:To investigate the changes of serumβ2 microglobulin(β2-MG),cystatin C(CysC)and urine microalbumin(mAlb)levels in patients with ureteral calculi before and after extracorporeal shock wave lithotripsy and their clinical significance.Methods Sixty-eight patients with ureteral calculi admitted to the hospital between June 2018 and June 2019 were selected as the observation group.35 volunteers who received physical elimination in the hospital during the same period were selected as the control group.Levels ofβ2-MG,Cys C and urine mAlb in the observation group were compared before and after treatment,and compared with those in the control group.Changes in serumβ2-MG,Cys C and urine mAlb levels and renal function indicators[blood urea nitrogen(BUN),serum creatinine(SCr)]in patients with different prognosis in the observation group after treatment were analyzed.The value of serumβ2-MG,Cys C and urine mAlb levels in the diagnosis and treatment of ureteral calculi was analyzed with ROC curve.The correlations between serumβ2-MG,Cys C and urine mAlb levels and renal function indexes were analyzed.Results Serumβ2-MG,Cys C and urine mAlb levels in the observation group before treatment were significantly higher than those in the same group after treatment or those in the control group(P<0.05).Serumβ2-MG,Cys C and urine mAlb levels,BUN and SCr in patients with residual stones were significantly higher than those in patients without(P<0.05).ROC curve analysis showed that the sensitivity and the area under the curve of combined detection of serumβ2-MG,Cys C and urine mAlb levels for evaluating the curative effect of extracorporeal shock wave lithotripsy on ureteral calculi were significantly higher/larger than those of single detection of the three(P<0.05).Partial correlation analysis showed that serumβ2-MG,Cys C and urine mAlb levels were positively correlated with BUN and SCr(P<0.05).Conclusion There are obvious changes of serumβ2-MG,Cys C and urine mAlb levels in patients with ureteral calculi before and after extracorporeal shock wave lithotripsy.The combined detection of the three indexes is helpful for the early diagnosis of ureteral calculi and the evaluation of renal function after lithotripsy.They can provide reference for protecting renal function in patients with ureteral calculi treated by extracorporeal shock wave lithotripsy.

Twenty-Two-Year Observation on Urinary Cadmium and β_(2)-Microglobulin in Inhabitants after Cessation of Cadmium-Exposure in Japan

Objective: This is an epidemiological survey that was conducted for 22 years to investigate the physical effects on inhabitants who had been exposed to cadmium (Cd) from processing of remnants discharged at the time of copper refinement. It was possible to obtain findings on physical effects 27 years after Cd exposure. Materials and Methods: Of the inhabitants who were 50 years old or younger in 1981 and who were living in the most contaminated area in the Kakehashi River basin, 68 (32 males and 36 females) who underwent all of the 5 screenings during the 22-year period were extracted as subjects. Early morning urine was collected for urinalysis, and Cd and ?2-MG concentrations were determined. Results: 27 years after cessation of Cd exposure, it was shown that urinary Cd concentrations were significantly decreased and urinary ?2-MG concentrations were significantly increased. Conclusion: Once exposed to Cd, it takes about 30 years for the Cd that remains in the body to decrease by half. Once renal tubular dysfunction occurs after Cd exposure, irreversible aggravation is inevitable.

血清胱抑素C、尿β_2微球蛋白和尿微量白蛋白水平对妊娠高血压早期肾损伤的临床意义

目的探讨血清胱抑素C（Cys-C）、尿β2微球蛋白（β2-MG）和尿微量白蛋白（U-MA）与孕妇妊娠高血压的相关性。方法妊娠高血压组52例：均选自2012年9月-2014年6月妇产科妊娠高血压患者（妊娠时间22周-34周）,正常妊娠组50例（妊娠时间21周-36周）,健康体检女性对照组50例,分别测定其血清胱抑素C（Cys-C）、尿β2微球蛋白（β2-MG）和尿微量白蛋白（U-MA）。结果妊高症组患者血清胱抑素C、尿β2微球蛋白和尿微量白蛋白的水平明显高于正常妊娠组和健康体检女性对照组,差异均有统计学意义（P〈0.05）。结论妊娠高血压时血清胱抑素C、尿β2微球蛋白和尿微量白蛋白水平明显升高,且对妊娠高血压早期肾损伤有明显的临床诊断价值。

血清胱抑素C和血尿β_2-微球蛋白对2型糖尿病早期肾损害的诊断价值

目的探讨血清胱抑素C、血/尿β2-微球蛋白联合检测在2型糖尿病肾病中的应用价值。方法将120例2型糖尿病肾病患者按尿清蛋白排泄率分为A、B、C三组,用全自动生化分析仪检测血清胱抑素C,化学发光免疫分析仪检测血/尿β2-微球蛋白,对检测结果采用SAS统计软件进行统计学处理作对比分析。结果各期2型糖尿病肾病患者血清胱抑素C、血/尿β2-微球蛋白水平均明显升高,与对照组比较,有显著性差异(P<0.05或P<0.01);120例2型糖尿病肾病患者血清胱抑素C与血/尿β2-微球蛋白呈正相关(r为0.428,0.366;P<0.01,P<0.01)。结论血清胱抑素C、血/尿β2-微球蛋白联合检测在协助临床做好2型糖尿病肾病早预防、早发现、早治疗方面有其积极意义。

ACEI对糖尿病肾病患者尿α_1-MG及β_2-MG的影响

目的 探讨ACEI类药 -西拉普利对 2型糖尿病并肾病患者的尿α1,β2 MG ,尿白蛋白的影响。方法 患者均伴有DM肾病 (DN) ,随机分成两组 ,治疗组 (2 8例 )服西拉普利 ,对照组 (2 8例 )服钙离子拮抗剂硝苯地平控释片。分别于服药前及后 4周、8周、16周用放射免疫法 (RIA)测定患者尿α1 MG、β2 MG及Alb。结果 西拉普利有明显降低 2型DM肾病患者尿α1 MG、β2 MG的排出。且对α1 MG的降低作用更显著 (P <0 .0 1)。结论 西拉普利适用于DN患者 ,尤其是α1

石家庄市健康体检人群尿微量白蛋白和β_2微球蛋白分析

目的探讨尿微量白蛋白和β_2微球蛋白在健康体检中的应用价值。方法应用比浊法检测417例健康体检者尿微量白蛋白和β_2微球蛋白含量,并将其结果与其他检测指标进行相关性分析。结果尿微量白蛋白和β_2微球蛋白在性别中差异有统计学意义(P<0.05);尿微量白蛋白和β_2微球蛋白与收缩压、尿比重、血尿素氮、肌酐等检测指标均呈正相关(P<0.05)。此外,尿微量白蛋白与β_2微球蛋白也呈正相关(P<0.01)。结论在制定普通人群中尿微量白蛋白和β_2微球蛋白的正常范围时,应该注意性别的差异;尿微量自蛋白和β_2微球蛋白作为反映肾功能的敏感指标,可用于健康体检。

急性脑卒中血清、尿、脑脊液β_2-微球蛋白的临床研究

目的 探讨急性脑卒中与血清、尿、脑脊液 β2 MG的相关性及其临床意义。方法 应用放射免疫法测定10 8例脑梗死和 94例脑出血 1周内 β2 MG ,并在 1～ 3周后进行复查。同时测定部分尿β2 MG含量 ,部分做了脑脊液β2 MG含量动态观察。结果 1周内血清、尿、脑脊液 β2 MG含量 (μg/L)脑梗死和脑出血组分别 2 417± 10 94和 2 0 0 4± 10 2 9、16 9 1± 186 8和 2 76 5± 2 12 0、1994± 12 83和 2 983± 1179,与正常对照组比较明显升高 ,P <0 0 5或P <0 0 1或P <0 0 0 1。治疗 1～ 3周后复查均有不同程度的减低。结论 急性脑卒中与血、尿、脑脊液 β2 MG有明显相关性 。

糖尿病和糖尿病肾病患者白蛋白、β_2-微球蛋白、粘蛋白含量及l^(131)邻碘马尿酸钠肾图分析

[目的 ]观察糖尿病及糖尿病肾病时尿白蛋白、β2 微球蛋白、粘蛋白含量及I13 1 邻碘马尿酸钠肾图曲线变化关系 .[方法 ]用放射免疫检测法测定白蛋白、β2 微球蛋白、粘蛋白 ,I131 邻碘马尿酸钠肾图采用核多功能测定仪的两个放射性探测器直接在体表分别探测两肾区的时间 放射性曲线 .[结果 ]78例糖尿病患者中尿白蛋白、血尿 β2 微球蛋白和尿粘蛋白均增高 ,但血粘蛋白无变化 ;18例行I131肾图 ,其中有 1例肾图曲线的C段排泄有变化外 ,其余正常 .40例糖尿病肾病患者中尿白蛋白、血尿 β2 微球蛋白、尿粘蛋白明显增高 ,血粘蛋白改变不明显 .I131 邻碘马尿酸钠肾图曲线随着血糖及尿白蛋白、血尿 β2 微球蛋白、尿粘蛋白含量的增高而出现不同类型的改变 .[结论 ]尿白蛋白、血尿 β2 微球蛋白、尿粘蛋白对糖尿病肾病具有早期诊断价值 ,与此同时结合I131 邻碘马尿酸钠肾图 。

硝苯地平对高血压患者血和尿β_2-微球蛋白、白蛋白、及透明质酸的影响

目的：观察硝苯地平对轻中度高血压患者血、尿微球蛋白及肾功能的影响。 方法：测定 ２０ 例正常人和 ８０ 例轻中度高血压患者用药前后血压、血和尿 β２ ┐微球蛋白（β２ ┐ Ｍ Ｇ）、透明质酸（ Ｈ Ａ）、尿白蛋白（ Ａ Ｌ Ｂ）、尿素氮（ Ｂ Ｕ Ｎ）、肌酐（ Ｃｒ）等。 结果：患者前五项指标均高于正常人。用药后血压、血和尿 β２ ┐ Ｍ Ｇ、 Ｈ Ａ、尿 Ａ Ｌ Ｂ均明显下降。 结论：硝苯地平可有效控制血压，同时降低血和尿 β２ ┐ Ｍ Ｇ、 Ｈ Ａ、尿 Ａ Ｌ Ｂ，改善肾功能。

川芎嗪与ACEI联用对伴轻度高血压2型糖尿病患者尿α_1-MG、β_2-MG的影响

目的探讨川芎嗪并用ACEI对伴轻度高血压2型糖尿病患者尿α1-微球蛋白(α1-MG)、β2-微球蛋白(β2-MG)的影响。方法45例2型DM患者均伴轻度高血压,随机平均分成两组,治疗组(23例)服ACEI-苯那普利并用川芎嗪注射液,对照组(22例)服ACEI-苯那普利;分别与服药前及后2周、4周、8周用放射免疫法(RIA)测定患者尿α1-MG、β2-MG及尿白蛋白(Alb)。比较两组服药前后血压的变化。结果川芎嗪并用ACEI对伴轻度高血压2型糖尿病患者尿α1-MG、β2-MG排泄量的降低作用较单用ACEI类药的降低作用更明显(P<0.01),且对α1-MG的降低作用更显著(P<0.01)。其降低α1-MG、β2-MG及AER的作用与其降低血压的作用无明显相关关系(P>0.05)。结论ACEI类药非常适用于T2DM患者,尤其是α1-MG、β2-MG升高者,不论其血压正常或轻度升高。但合用川芎嗪其疗效更佳。这对阻止DN的发生及发展有着非常重要的临床意义。

2型糖尿病肾病患者并发肌少症与血清25-羟维生素D3及尿白蛋白肌酐比值的相关性

目的探究2型糖尿病肾病患者并发肌少症与血清25-羟维生素D3[25(OH)D3]及尿白蛋白肌酐比值(UACR)的相关性。方法选取2020年1月~2021年6月河北医科大学第一医院收治的315例2型糖尿病肾病患者作为研究对象,根据是否发生肌少症分为肌少症组(97例)和非肌少症组(218例),分析25(OH)D3及UACR与肌少症的相关性。结果肌少症组25(OH)D3水平低于非肌少症组,UACR水平高于非肌少症组,差异均有统计学意义(P<0.05);肌少症组四肢骨骼肌量指数(ASMI)与UACR呈负相关(P<0.05),与25(OH)D3呈正相关(P<0.05);UACR预测2型糖尿病肾病患者并发肌少症的曲线下面积为0.969(0.955~0.983),截断值为31.180 mg/g(灵敏度为92.8%,特异度为100.0%);25(OH)D3预测2型糖尿病肾病患者并发肌少症的曲线下面积为0.931(0.917~0.945),截断值为25.077 ng/mL(灵敏度为89.7%,特异度为82.1%)。结论2型糖尿病肾病患者肌少症的发生与血清25(OH)D3及UACR密切相关,应注意相关指标的筛查并进行相应的干预。

低剂量ACEI对伴血压正常或轻度高血压2型糖尿病患者尿α_1-MG、β_2-MG的影响

目的 探讨低剂量血管紧张素转换酶抑制剂 (ACEI)类药对伴血压正常或轻度高血压的 2型糖尿病 (T2 DM)患者尿α1 - MG、β2 - MG的影响。方法 6 3例 T2 DM患者中 ,血压正常 31例 ,血压轻度升高 32例。随机分成两组 ,治疗组服低剂量 ACEI,对照组服钙离子拮抗剂 ;两照组均含轻度高血压者。比较两组服药前后血压变化 ;分别于服药前及后 16周、 2 4周用放射免疫法 (RIA)测定患者尿 α1 -微球蛋白 (α1 - MG)、β2 -微球蛋白 (β2 -MG)及 2 4 h尿白蛋白 (Alb)。结果 ACEI类药有明显降低 T2 DM患者尿 α1 - MG、β2 - MG的作用。以降低 α1 - MG的作用更显著 (P<0 .0 1)。其降低 α1 - MG、 β2 - MG及 Alb的作用与其降低血压的作用无明显相关性 (P>0 .0 5 )。结论 低剂量 ACEI类药非常适用于血压正常或轻度升高的 T2 DM患者 ,尤其是α1 - MG升高者 。

β_2-MG RIA在消化道恶性肿瘤诊断中的临床价值

目的 探讨尿 β2 -MG含量与消化道恶性肿瘤之间的相关性。方法 采用放射免疫分析 (RIA)法测定正常对照组、消化道恶性肿瘤患者的尿液并进行统计分析。结果 2 12例各类消化系统恶性肿瘤患者的尿 β2 -MG都明显高于正常对照组 ,差异有显著性P <0 0 1。结论 尿β2 -MG可作为消化系统恶性肿瘤的标志物之一 。