血液透析患者血浆硫酸吲哚酚与左心室肥厚的相关性

目的探究血液透析患者左心室肥厚的相关危险因素。方法纳入慢性肾脏病(CKD)血液透析患者190例,检测生化指标,进行心脏超声检查,将患者分为左心室肥厚组和非左心室肥厚组。采用高效液相色谱-电喷雾-串联质谱技术对血浆中硫酸吲哚酚(IS)进行检测。采用Spearman相关或Pearson相关分析IS与其他生化或临床指标的关系。采用线性回归分析IS与左心室质量指数(LVMI)的关系,同时采用Logistic回归模型分析IS和左心室肥厚(LVH)的关系。结果共入组190例,男117例,女73例,年龄(57.3±14.2)岁,LVH患病率达65.8%。单因素线性回归显示,血浆硫酸吲哚酚(IS)与左心室质量指数(LVMI)呈正相关(β=7.05,P=0.01),校正各种危险因素后,IS与LVMI仍呈正相关(β=4.1,P=0.02)。采用Logistic回归分析硫酸吲哚酚(IS)与左心室肥厚(LVH)的关系,校正各种危险因素后,血浆硫酸吲哚酚(IS)与左心室肥厚(LVH)独立正相关(β=6.55,OR=0.70,95%CI=0.63~0.77,P=0.03)。结论 CKD血液透析患者血浆IS与LVMI呈独立正相关,血浆IS是LVH的独立危险因素。     

化学药物诱导的大鼠急性肾损伤模型中肾损伤分子-1表达的研究

目的：观察肾损伤分子-1(kidney injury molecule-1,Kim-l)在由顺铂、庆大霉素、环孢素诱导大鼠急性肾损伤(acute kidneyinjury,AKI)模型肾组织内的变化,探讨其与AKI之间的相关性。 方法：建立庆大霉素、顺铂、环孢素诱导大鼠AKI模型,运用实时荧光定量PCR法检测肾Kim-1基因表达水平,Western blot法检测肾脏Kim-1蛋白表达水平,分析肾Kim-1表达水平与急性肾损伤的相关性。结果：病理学检查发现顺铂、庆大和环孢素对大鼠肾脏造成不同程度的肾小管损伤,所建AKI模型成功。各模型组与对应对照组比较,肾Kim-l mRNA水平均高于阴性对照组,差异具有统计学意义（P 均＜0.05）;肾Kim-l蛋白在各阴性对照组内呈阴性结果,而在顺铂、庆大和环孢素AKI模型组内均呈阳性表达。结论：化学药物诱导AKI发生时,肾Kim-1基因转录和蛋白表达水平与肾损伤直接相关,为以尿Kim-1作为预测早期肾损伤的生物标志物提供可靠依据。     

尿中肾损伤分子1水平升高对大鼠早期肾损伤的预测作用

目的评价尿中肾损伤分子1(KIM-1)对大鼠早期肾损伤的预测作用。方法制备顺铂、庆大霉素和环孢素诱导的大鼠肾损伤模型。顺铂模型大鼠于单次ip给药后第3,5,6和7天,庆大霉素模型于首次ip给药后第3,7,10和13天,环孢素模型于首次ig给药后第8,15,36和53天通过腹主动脉取血,分离血清。各组大鼠于处死前24 h收集尿液。用自动生化仪检测血清肌酐(SCr)和血尿素氮(BUN)及尿肌酐(UCr)水平,采用ELISA法检测尿KIM-1水平,HE染色进行肾脏组织病理学检查。结果与正常对照组相比,顺铂模型大鼠单次给药后第3天肾组织病理改变不明显,而尿KIM-1升高了4.7倍,SCr和BUN升高了0.3和0.7倍;第5和6天,KIM-1升高了10.0和8.7倍,SCr升高了1.9和3.3倍,BUN升高了3.0和5.1倍,第5天肾组织出现明显的病理改变;第7天,KIM-1水平升高了16.5倍,SCr和BUN水平略降,为正常对照组的1.2和3.0倍。庆大霉素模型大鼠,与正常对照组比较,于首次给药后第7天,SCr和BUN水平和肾组织未见明显改变,KIM-1水平升高了2.6倍;第10和13天,SCr水平升高了1.7和1.6倍,BUN升高了2.0和1.9倍,KIM-1升高了12.5和33.9倍,第10天肾组织出现明显的病理改变。环孢素模型大鼠,与正常对照组比较,在第8天,SCr和BUN水平和肾组织未见异常,KIM-1升高了正常对照组的0.6倍;第15,36和53天,KIM-1分别升高了1.7,4.3和9.3倍,SCr分别为1.0,1.0和1.2倍,BUN分别升高了0.4,0.6和1.2倍,肾组织在第53天时出现明显的病理改变。顺铂模型组SCr,BUN和KIM-1的受试者操作特性曲线的曲线下面积(AUC)分别为0.934,0.953和0.979,庆大霉素模型组SCr,BUN和KIM-1的AUC分别为0.877,0.713和0.932,环孢素模型组SCr,BUN和KIM-1的AUC分别为0.668,0.766和0.976。结论在顺铂、庆大霉素和环孢素诱导的肾损伤模型中,尿KIM-1可用于早期肾损伤的预测。     

黄芪抗顺铂致肾损伤的研究进展

顺铂（DDP）是一种广谱抗癌药,但由于在临床使用后,在患者体内代谢会产生大量的自由基,很容易引起肾毒性,造成肾损伤.因而在临床使用上往往要采取一定的措施减轻其对患者的肾损伤.黄芪味甘性温,入脾、肺经,具补气固表利水、养血生肌托毒之功.现代药理研究发现黄芪含多种皂苷、多糖、氨基酸、叶酸及硒、锌、铜等多种微量元素,具有增强免疫力、抗氧化、抗自由基等作用.     

中药肾复舒颗粒对慢性肾衰患者血硫酸吲哚酚浓度的影响

目的探讨慢性肾衰竭患者口服中药肾复舒颗粒和血液透析对血硫酸吲哚酚(IS)浓度的影响。方法 (1)慢性肾衰患者110例,分为口服肾复舒组(56例,口服肾复舒颗粒15 g,2~3次·d-1,3个月)和血液透析组(54例,普通血液透析2~3次/周,3个月);正常对照组50例。(2)入组者清晨取空腹静脉血并留取尿液、粪便。(3)自动分析仪测生化指标,高效液相色谱-荧光法检测IS浓度。结果正常对照组血IS水平为(0.085±0.064)μg·mL~(-1),口服肾复舒组血为(1.046±0.193)μg·mL~(-1),血液透析组为(5.002±1.032)μg·mL~(-1),各组差异有统计学意义(P<0.01);肾复舒组粪便检测出较高浓度的IS(0.965±0.42)μg·mL~(-1),正常对照组和血液透析组均未测出。结论口服肾复舒颗粒能降低慢性肾衰患者血IS浓度,血液透析组IS浓度下降不明显。     

肾损伤分子1对顺铂诱导的大鼠急性肾损伤的预测研究

目的 对肾损伤分子1 (KIM-1)预测顺铂诱导的大鼠急性肾损伤进行研究.方法 以顺铂为工具药,诱导大鼠急性肾损伤模型.采集尿样、肾组织样本,对肾组织样本进行病理切片检查,以确定造模是否成功.用ELISA法测定尿样中KIM-1蛋白含量;RT-PCR法检测大鼠肾脏KIM-1基因表达水平;Western blotting法检测大鼠肾组织中KIM-1的蛋白含量,并通过免疫组化法定性定位分析大鼠肾组织中KIM-1蛋白表达情况,以确定急性肾损伤发生时KIM-1是否可以作为敏感的检测指标.结果 当模型组大鼠肾脏皮髓交界处出现程度不等的肾小管扩张,肾小管上皮细胞变性、坏死脱落,基底膜裸露等病理改变时,ELISA法检测尿KIM-1,RT-PCR法和Western blotting法检测肾组织中的KIM-1表达水平均明显升高,免疫组化显示模型组所有大鼠在肾皮髓交界部位可见大量的染色阳性的肾小管,该染色阳性区域与组织病理学检查中的异常肾小管分布区域基本一致.结论 KIM-1可作为一种敏感的生物标志物对顺铂诱导的大鼠急性肾损伤进行预测.     

左旋肉碱改善顺铂诱导肾损伤机制的相关研究

左旋肉碱可有效改善某些药物引起的肾损伤,其在顺铂诱导的急性肾损伤中起保护作用。多数研究认为左旋肉碱主要通过抗氧化、抗炎及抗凋亡作用发挥对顺铂肾毒性的保护作用,但目前发现其机制还涉及其他方面。该文就左旋肉碱改善顺铂肾损伤的相关研究综述如下。     

促红细胞生成素对顺铂急性肾损伤的保护作用

目的：探讨促红细胞生成索（Erythopoietin,Epo）对顺铂（CDDP）急性肾损伤的保护作用及机制。方法：建立大鼠CDDP急性肾损伤动物模型,将SD大鼠随机分为生理盐水（NS）组、CDDP组及Epo治疗（CDDP＋Epo治疗）,观察各组血清尿素氮（BUN）、血肌酐（Scr）和肾组织匀浆超氧化物歧化酶（SOD）、丙二醛（MDA）及肿瘤坏死因子-α（TNF—α）的变化。结果：Epo治疗组血清BUN、Scr及MDA、TNF-α较CDDP组显著下降（P〈0．05）,SOD显著升高（P〈0．05）。结论：Epo可提高SOD,降低TNF—α对CDDP急性肾损伤具有保护作用。     

茶多酚对顺铂所致肾损伤保护作用的实验研究

目的　 研究茶多酚 (TP)对顺铂 (DDP)所致肾毒性的保护作用及其机制。 方法 　将小鼠随机分为 4组 :对照组、DDP组、DDP +低剂量TP组、DDP +高剂量TP组 ,分别腹腔注射生理盐水、顺铂 2mg/kg ,喂饲TP0 5g/kg ,1 0g/kg ,测定血清中尿素氮 (BUN)、肌酐 (Cr)和肾组织匀浆中超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶 (GSH Px)活性及丙二醛 (MDA)含量 ,观察肾脏病理结构的变化。 结果 　DDP组小鼠血清中BUN及Cr值升高 ,与对照组比较差异有极显著意义 (P <0 0 1) ,加入高剂量TP后 ,BUN及Cr值明显低于DDP组 (P <0 0 5 )。给予DDP后 ,肾组织中SOD、GSH Px活性降低 ,MDA含量升高 ,与对照组比较 ,差异有显著性 (P <0 0 5 ,P <0 0 1)。喂饲TP后SOD、GSH Px值有所上升 ,MDA下降 ,DDP +低剂量TP组与DDP组比较 ,SOD、MDA两项指标差异有显著性 (P <0 0 5 ) ,但与对照组比较 ,3项指标均存在显著差异 (P <0 0 5 ) ;DDP +高剂量TP组SOD、GSH Px值升高 ,MDA含量降低较明显 ,与DDP组比较差异有显著性 (P <0 0 5 ,P <0 0 1)。光镜下肾组织超微结构亦见改善。 结论 　TP在一定程度上可缓解DDP所致的肾损伤 ,其机制可能与抗氧化功能有关。     

顺铂诱导急性肾损伤关键基因的筛选和调控网络的构建

目的　通过生物信息学鉴定顺铂诱导的急性肾损伤中的关键基因和通路,为急性肾损伤的治疗提供潜在靶点。方法　数据提取时间：建库至2021年3月1日。我们先从基因表达综合数据库（GEO）下载了GSE106993和GSE153625数据集,并使用R语言筛选出差异基因,再采用基因本体论（GO）富集分析和京都基因与基因组大百科全书数据库（KEGG）分析鉴定共同差异基因的主要功能,接着使用STRING数据库对共同的差异基因构建互作网络,并用Cytoscape筛选出关键基因。然后运用TransmiR v2.0数据库和miRWalk 2.0数据库构建转录因子（TF）/微小RNA（miRNA）/信使RNA（mRNA）调控网络。最后通过ETMC数据库筛选出靶向关键基因的中草药。结果　我们发现在顺铂诱导的急性肾损伤模型中上调基因有817个,下调基因有769个。肿瘤坏死因子信号通路、P53信号通路、代谢信号通路均是顺铂诱导的急性肾损伤的重要通路。通过蛋白互作网路,我们鉴定出8个关键基因（TrP53、EGF、Stat3、Jun、Casp3、Cdh1、Ptgs2、CAT）。并且构建了TF/miRNA/mRNA调控网络,TF 2个,miRNA 4个,mRNA 214个。ETMC数据库分析结果显示桑叶和半夏可用于顺铂诱导的急性肾损伤的治疗。结论　本研究通过生物信息学分析筛选出顺铂诱导的急性肾损伤中的8个关键基因和3个重要信号通路,为顺铂诱导急性肾损伤的治疗提供靶点。桑叶和半夏两味中药有望成为治疗急性肾损伤的中草药。     

Karyomegaly of tubular cells as early stage marker of the nephrotoxicity induced by ochratoxin A in rats.

Cases of karyomegaly were described by Sclare and by Mihatch in patients affected with tubular-interstitial nephropathy. The Karyomegalic cells showed enlarged nuclei with accumulation of genetic material. No aetiology was suggested. Our study of rats experimentally intoxicated by ochratoxin A, a well-known nephrotoxic compound, indicates the presence of karyomegaly with alteration of the tubular tissue. In control animals no karyomegalic cells were detected. These observations suggest that karyomegaly with megacytosis may be caused by the nephrotoxic ochratoxin A in the kidney. In addition abnormal mitosis together with karyomegalic cells were observed at an earlier stage of the intoxication (30 days) suggesting possible regeneration if the OTA insults are stopped. After 90 days of treatment, the degeneration increased and only karyomegalic and apoptotic-like cells were observed indicating that the regeneration no longer occurs and that the degeneration becomes irreversible.     

组织端粒酶活性和细胞调亡指数的测定在胃癌早期临床诊断的意义

目的：探讨胃癌组织中端粒酶活性和细胞凋亡指数与正常组织相比较在癌组织中的变化,及其在胃癌早期诊断和临床分期方面的意义。方法：采用端粒扩增法（TRAP）检测端粒酶活性,应用免疫组织化学方法及TUNEL法检测胃癌组织的细胞凋亡指数。结果：胃粘膜活检标本中胃癌组织端粒酶阳性率达88．1％相近,提示大部分胃癌组织端粒酶处于活化状态。此结果在胃癌的早期诊断中具有重要的意义。     

数字震动感觉阈值联合踝肱指数在诊断糖尿病患者早期并发症中的意义

目的 验证数字震动感觉阈值联合踝肱指数在诊断糖尿病早期并发症中的作用.方法 设定新确诊的100例无手足麻木、灼痛、刺痛、视物不清、头痛、头昏等感觉的2型糖尿病患者为实验组,设定该地区100名健康人作为对照组,分别分组采用数字震动感觉阈值法、踝肱指数检测法及上述两者联合使用法对此200名实验对象进行检测,并将检测结果进行比较.结果 与单独检测数字震动感觉阈值或踝肱指数相比,联合检测发展糖尿病早期并发症的概率要明显高于单独检测组.联合测量组与数字震动感觉阈值测量组间差异有统计学意义（P＜0.05）.结论 联合检测数字震动感觉阈值结合踝肱指数,可提高糖尿病早期并发症的诊断率,值得临床推广.     

血浆降钙素原（PCT）测定对脓毒性休克早期诊断的价值

目的：评价血浆降钙素原（procalcitonin,PCT）对脓毒性休克患者早期诊断价值及其临床意义。方法：抽取38例休克患者外周血标本,作PCT检测和血培养。结果：两种方法相比,差异有明显的统计学意义,P〈0．01,PCT检验法灵敏性和特异性高。结论：PCT检验法较血培养灵敏,对休克的病因诊断及临床治疗具有指导意义。     

Epidemiological application of early markers of nephrotoxicity

This paper is a review of epidemiological studies in which sensitive markers of nephrotoxicity have been used to detect the early effects of chemicals on the kidney. Most of the studies are cross-sectional, and their objective was either to identify potentially nephrotoxic chemicals (organic solvents, heavy metals) in the working or general environment or to establish dose-response/effect relationships from which safe exposure levels can be defined (e.g., for cadmium and mercury vapour). A few longitudinal studies were conducted to determine the persistence of renal disturbances and to get information on their predictive value (e.g., microproteinuria in cadmium workers). Nephrotoxicity tests, which have proved to be the most useful in these epidemiological studies, rely on the determination of specific urinary proteins which, according to their size, reflect the functional integrity of the proximal tubule (e.g., retinol-binding protein or beta 2-microglobulin) or the glomerulus (e.g., albumin, immunoglobulin G). An increased urinary excretion of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase has been reported in several studies (e.g., in lead-exposed workers), but the pathological significance of this finding remains to be clarified, particularly when it is not associated with changes in the urinary excretion of specific proteins. Further work is needed to assess the usefulness of tests introduced more recently such as the assay of renal antigens in urine and the use of red-blood-cell membrane negative charges as an index of the glomerular polyanion. With the exception of microproteinuria observed in chronic cadmium poisoning, no epidemiological data are available on the prognostic value of subclinical renal effects caused by nephrotoxic chemicals.     

低剂量螺旋CT对以亚实性肺结节为主要表现的早期肺腺癌的诊断意义

目的 评价低剂量螺旋CT对以亚实性肺结节为主要表现的早期肺腺癌的诊断意义.方法 回顾性选择上海市浦东新区周浦医院2018年1月至2019年6月46例CT表现为亚实性肺结节并经手术确诊为早期肺腺癌病人的临床资料,根据肺结节的密度类型分为有实性成分的混合性磨玻璃结节组和纯磨玻璃结节组.根据病理结果分为浸润前组(包括微浸润性...     

Metabolomics analysis reveals elevation of 3-indoxyl sulfate in plasma and brain during chemically-induced acute kidney injury in mice: investigation of nicotinic acid receptor agonists

An investigative renal toxicity study using metabolomics was conducted with a potent nicotinic acid receptor (NAR) agonist, SCH 900424. Liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) techniques were used to identify small molecule biomarkers of acute kidney injury (AKI) that could aid in a better mechanistic understanding of SCH 900424-induced AKI in mice. The metabolomics study revealed 3-indoxyl sulfate (3IS) as a more sensitive marker of SCH 900424-induced renal toxicity than creatinine or urea. An LC-MS assay for quantitative determination of 3IS in mouse matrices was also developed. Following treatment with SCH 900424, 3IS levels were markedly increased in murine plasma and brain, thereby potentially contributing to renal- and central nervous system (CNS)-related rapid onset of toxicities. Furthermore, significant decrease in urinary excretion of 3IS in those animals due to compromised renal function may be associated with the elevation of 3IS in plasma and brain. These data suggest that 3IS has a potential to be a marker of renal and CNS toxicities during chemically-induced AKI in mice. In addition, based on the metabolomic analysis other statistically significant plasma markers including p-cresol-sulfate and tryptophan catabolites (kynurenate, kynurenine, 3-indole-lactate) might be of toxicological importance but have not been studied in detail. This comprehensive approach that includes untargeted metabolomic and targeted bioanalytical sample analyses could be used to investigate toxicity of other compounds that pose preclinical or clinical development challenges in a pharmaceutical discovery and development.     

The use of a change in gentamicin clearance as an early predictor of gentamicin-induced nephrotoxicity

A retrospective review was undertaken in 744 patients who were dose-individualized with gentamicin once daily to evaluate a change in gentamicin clearance as a potential predictor of nephrotoxicity. The definition of nephrotoxicity was chosen to be a change in creatinine clearance greater than 20%. Similarly, a change in gentamicin clearance of greater than 20% was also considered a possible index of nephrotoxicity. Four criteria were developed to assess the usefulness of gentamicin clearance as a predictor of nephrotoxicity. Following the application of the inclusion/exclusion criteria, 132 patients were available for the analysis. The sensitivity, specificity, positive predictive value, and negative predictive value were assessed for each of the criteria. Receiver operating characteristic (ROC) curves were produced to determine if an optimum value in the change of gentamicin clearance could be found to maximize sensitivity and specificity. The overall incidence of nephrotoxicity based on a decrease in creatinine clearance by 20% or more was 3.8%. Women were overrepresented in the nephrotoxic group [71.4% versus 40.1% (P = 0.0025)]. Patients with nephrotoxicity had statistically longer treatment periods, increased cumulative dose, and more dosing predictions (P < 0.05 in each case). The sensitivity of the criteria ranged from 43 to 46%, and specificity ranged from 93 to 99%. The positive and negative predictive values ranged from 63 to 94% and 86 to 89%, respectively. In those patients in whom nephrotoxicity was predicted from a change in gentamicin clearance, this change occurred on average 3 days before the change in creatinine clearance (P < 0.05). A change in gentamicin clearance to predict nephrotoxicity may be a useful addition to current monitoring methods, although it is not the complete answer.     

原发性肝癌早期诊断中甲胎蛋白异质体检测的意义

目的探讨甲胎蛋白异质体（AFP—L3）在原发性肝癌（PLC）早期诊断的意义。方法分别用微量离心柱法和电化学发光法检测170例治疗前PLC患者和130例慢性肝病患者血清中的AFP-L3和AFP。结果PLC组的AFP—L3敏感性和中位水平分别为84．12％和16．85,高于良性肝病组（P〈0．05）。20〈AFP％200ng／ml时AFP—L3的敏感性为74．36％,特异性为74．65％。AFP—L3水平及阳性率随肝癌分期和肿瘤增大升高,I期肝癌和小肝癌的敏感性分别为60．87％和66．67％。结论AFP—L3在PLC早期诊断中具有重要临床价值。