尿毒症相关毒素研究进展

自21世纪70年代提出"中分子学说"至今,对尿毒症毒素的含义及尿毒症发病机制的研究仍有许多争议,目前临床仍然以水溶性小分子物质作为尿毒症判定及肾脏替代治疗疗效的指标,但ESRD患者预后不佳~([1-3])促使人们深入尿毒症毒素的研究,这将有助于提高临床对尿毒症的诊治水平,本文就近年来尿毒症毒素作用的新观点进行简要综述.     

尿毒症毒素：中分子学说

给出了紧连通可定向带边３－流形的一种表示方法。     

对尿毒症毒素的新认识

在慢性肾功能不全进行性加重后，体内有２００种以上物质的水平比正常人增高，其中有些物质具有毒性作用。这些具有毒性作用的物质在体内积聚，是引起尿毒症症状、代谢紊乱和多个系统功能失调的主要原因之一。近二十年来关于大、中分子尿毒症毒素的研究进展相对迟缓，但近...     

尿毒症毒素—来自糖基化终末产物？

提出了一种应用于过程式语言的动态部分求值技术，并实现了一个类如ＰＡＳＣＡＬ语言的部分求值器。     

尿毒症毒素与心脏损伤的再认识

心血管疾病(CVD)是慢性肾脏病(CKD),尤其是终末期肾病患者最常见的并发症及死亡原因之一。近年来,研究证实CKD患者及血液透析(HD)患者发生CVD及全因死亡率与蛋白结合毒素的蓄积密切相关。蛋白结合毒素是一类很难通过单纯HD清除的物质,大部分分子质量大于500 Da,与蛋白结合后导致蛋白自身分子结构、电荷甚至功能发生变化,抑或可能导致其他组织、器官损伤。目前研究相对较多的是同型半胱氨酸、硫酸吲哚酚、硫酸对甲酚等物质对肾脏及心血管的毒性,其可能的致病机制包括刺激内皮细胞或白细胞产生自由基,影响内皮细胞和白细胞的相互作用,损伤内皮细胞,促进血管平滑肌细胞增殖,导致动脉粥样硬化、心脏的纤维化等。     

用噬菌体展示技术筛选幽门螺杆菌细胞毒素相关蛋白基因结合蛋白的研究

目的筛选幽门螺杆菌细胞毒素相关蛋白（CagA）基因结合蛋白，探索CagA致病机理。方法应用噬菌体展示技术，以幽门螺杆菌CagA基因片段作为固相筛选分子，对噬菌体人胃细胞cDNA文库进行4轮“吸附-洗脱-扩增”富集，噬斑裂解液PCR扩增后，进行DNA序列分析和同源性生物信息学搜索，确定编码结合蛋白的种类。结果噬菌体经富集后，筛选出36个阳性克隆，构建了克隆载体。序列测定后经过同源性搜索，确定幽门螺杆菌CagA基因共编码核纤层蛋白B1和胰岛素样生长因子结合蛋白2两种已知蛋白。结论用噬菌体人胃cDNA文库筛选得到幽门螺杆菌CagA基因DNA结合蛋白，为研究CagA致病机理，幽门螺杆菌疫苗的研制和治疗等提供依据。     

高通量血液透析清除尿毒症毒素疗效观察

目的　探讨高通量血液透析 (HPD)的临床应用价值。方法　比较常规血液透析(CHD)与HPD对尿毒症小分子毒素尿素氮 (BUN)、肌酐 (Cr)、磷 (P3 )及中大分子毒素 β2 微球蛋白( β2 M )、全段甲状旁腺激素 (iPTH)、瘦素 (Leptin)的清除效果。 结果　两种透析方法清除小分子毒素BUN、Cr效果均良好 ,而对血磷及中大分子毒素清除效果则有显著性差异 ,CHD治疗后P3 、β2 M、iPTH和Leptin下降率分别为 ( 4 3 .2 2± 6.0 9) %、( -3 .0 4± 7.91) %、( 2 5 .91± 6.5 7) %和 ( 4 .5 9± 2 .61) % ,HPD治疗后P3 、β2 M、iPTH和Leptin下降率分别为 ( 5 3 .86± 8.0 6) %、( 4 1.46± 8.18) %、( 5 1.5 6± 7.0 6) %和 ( 3 6.73± 11.78) %。结论　HPD能提高血磷及中大分子毒素的清除率 ,使透析治疗更充分 ,从而降低透析远期并发症 ,该法安全、高效 ,不需昂贵设备 ,可推广使用     

网膜结合蛋白升高提示内脏脂肪增加

根据脂肪的分布位置,脂肪可被分为两类:皮下脂肪和内脏脂肪。如果说皮下脂肪很坏的话,内脏脂肪更坏。即使一个人看起来很瘦,他也可能有内脏脂肪。如果有内脏脂肪,那么他患2型糖尿病和心脏病的风险就增加了。这时候瘦的人怎么才能知道自己有没有内脏脂肪呢?最近科学家发现血液中的一种蛋白质升高,提示患者内脏周围有脂肪堆积。     

定量检测幽门螺杆菌细胞毒素相关蛋白基因A方法的建立

目的建立定量检测幽门螺杆菌（Ｈｐ）细胞毒素相关蛋白基因Ａ（ｃａｇＡ）的方法。方法以含ＨｐｃａｇＡ片段的质粒（ｐＭＣ３）作为外参照品，在微孔板中对聚合酶链反应（ＰＣＲ）扩增ｃａｇＡ的产物进行辣根过氧化物酶标记探针的杂交及酶促显色以定量检测ｃａｇＡ阳性Ｈｐ。结果当ＰＣＲ反应体系中原始模板为１～１０５拷贝，循环次数小于或等于２５时，原始模板以相对固定的指数形式增加，在该范围内适宜定量分析。通过对２０份已知Ｈｐ菌株ｃａｇＡ的检测，符合率达１００％，观察结果的敏感度较电泳法提高了２００倍。定量检测不同胃黏膜组织中ｃａｇＡ阳性Ｈｐ，检出底线为６拷贝／毫克组织。结论本方法特异性强，敏感度高，对研究Ｈｐ与消化道疾病的关系及建立定量检测其他微生物的方法均有实用价值     

Super high‐flux hemodialysis provides comparable effectiveness with high‐volume postdilution online hemodiafiltration in removing protein‐bound and middle‐molecule uremic toxins: A prospective cross‐over randomized controlled trial

Although high‐volume postdilution online hemodiafiltration (ol‐HDF) is superior to high‐flux HD in removing all kinds of uremic toxins and improving survival, this treatment is not available in most HD centers. The present study was conducted to compare the effectiveness in removals of protein‐bound (indoxyl sulfate [IS]), middle‐molecule [beta‐2 microglobulin (B2M) and alpha‐1 microglobulin (A1MG)], and small‐molecule uremic toxins between super high‐flux HD (SHF‐HD), HD with a novel SHF dialyzer and high‐volume postdilution ol‐HDF in a noninferiority fashion. Fifteen prevalent HD patients were randomly allocated into two sequences of 12‐week treatment periods of SHF‐HD treatment and later high‐volume postdilution ol‐HDF period or vice versa. Each treatment period was divided by a wash‐out phase of 4‐week high‐flux HD. Twelve of 15 patients could complete the study. When compared with high‐volume postdilution ol‐HDF (convective volume of 24.4 ± 3.52 L), SHF‐HD provided comparable reduction ratio values of IS, B2M, and A1MG with mean difference of 5.87 (95% confidence interval [CI] ‐1.63, 13.37), 1.98 (95% CI,‐0.21, 4.18), and 22.96 (95% CI, ‐1.91, 47.83), respectively. The spKt/Vurea was not different. The predialysis levels of all uremic toxins at baseline and after 12‐week treatment did not differ between both groups. Although albumin loss in dialysate in SHF‐HD was greater than high‐volume postdilution ol‐HDF, the serum albumin levels after 12‐week SHF‐HD treatment were significantly higher than baseline. In conclusion, SHF‐HD provides noninferior effectiveness to high‐volume postdilution ol‐HDF in removing various uremic toxins with significantly increased serum albumin levels despite higher albumin loss. SHF‐HD might be an effectively alternative treatment when high‐volume postdilution ol‐HDF is not available.     

尿毒症桡动脉血管钙化与胎球蛋白A相关性研究

目的检测尿毒症患者桡动脉和血清中的胎球蛋白A,探讨其和血管钙化的关系。方法选取2007年1月至2010年12月大连医科大学附属第一医院肾内科收治的尿毒症患者32例,动静脉内瘘成形术时取废弃的桡动脉。另取上肢外伤患者9例,手术时取废弃的上肢血管作为对照组。血管行von kossa染色,茜素红染色检测钙化,免疫组化检测胎球蛋白A、α-SMA、cbfα1。同时检测血清中胎球蛋白A、甲状旁腺素(iPTH)、C-反应蛋白(CRP)等。结果尿毒症组血清胎球蛋白A低于对照组[(204.03±75.03)mg/L对(386.03±37.70)mg/L,P<0.01]。血清胎球蛋白A随血管钙化程度的加重逐渐减低。血管的胎球蛋白A染色积分随血管钙化程度的加重逐渐升高。血管钙化值与血清胎球蛋白A呈负相关(茜素红染色r=-0.572,P=0.001;Von kossa染色r=-0.518,P=0.002)。结论尿毒症患者血清胎球蛋白A水平以及桡动脉上的胎球蛋白A表达与血管钙化有关。     

Elevated fibrinogen fragment levels in uremic plasma inhibit platelet function and expression of glycoprotein IIb-IIIa

Hemostatic dysfunction is frequently noted in uremia, but the mechanisms responsible for it are poorly understood and are assumed to be multifactorial. Preliminary findings from our laboratory suggest that elevated levels of circulating fibrinogen fragments (FF) might contribute to the hemostatic defect in uremic patients. Defibrinated plasma obtained from chronic hemodialysis (HD) patients as well as normal subjects were examined by SDS-PAGE and immunoblotting and quantified by an immunoassay. In addition, endogenous FF isolated from normal and uremic plasma using affinity chromatography were examined by flow cytometry for their effect on glycoprotein (GP) IIb-IIIa receptor expression and tested for their ability to inhibit platelet aggregation. The mean FF concentration in uremic plasma (1.14 +/- 0.85 mg/ml) was noted to be eight times greater than in normal plasma (0.15 +/- 0.01 mg/ml) (P < 0.05). Moreover, the mean FF level decreased by 48.25% following HD (from 1.14 +/- 0.85 mg/ml to 0.59 +/- 0.33 mg/ml; P < 0.05). SDS-PAGE and immunoblotting experiments showed that the decrease was observed in both medium-sized (20-60 kDa) as well as large (>100 kDa) FF. Further, FF isolated from uremic plasma inhibited platelet aggregation by (46.8 +/- 18.1)% (P < 0.05) and the GP IIb-IIIa receptor expression by (28.0 +/- 7.6)% (P < 0.05 vs. control). The results show that (1) FF levels are elevated in uremic plasma, (2) HD results in significant decrease in FF and (3) endogenous FF inhibit platelet function, presumably via competitive binding to the fibrinogen receptor GP IIb-IIIa. The decrease in plasma levels of FF > 100 kDa following HD suggests that adsorption to the dialysis membrane contributes to their removal.     

The clinical effectiveness and safety of traditional Chinese medicine uremic clearance granule combined with high-flux hemodialysis in the treatment of uremic pruritus: A protocol for systematic review and meta analysis

Background:Skin pruritus is a common complication in patients with uremia. When the hemodialysis time of patients is extended, and the probability of skin pruritus is greater. Patients often have the symptoms of skin pruritus intolerable, affecting the normal sleep and normal life of patients. The patients with uremic pruritus often constant scratching and pruritus skin, resulting in broken skin, and further symptoms such as infection, and subsequent skin shedding, prurigo nodularis, and other adverse complications, aggravating the patient''s condition. Some patients will experience symptoms such as depression and insomnia due to skin pruritus, and simply scratching the skin lead to infection. Severely affected patients may even show suicidal tendency, endangering the physical and mental health of patients, and it is needed to give the effective treatment to patients. Hemodialysis is a common treatment for uremic pruritus, which can effectively relieve the pruritus symptoms of patients. The drugs can also relieve the symptoms and improve the degree of pruritus in patients. And some studies show that traditional Chinese medicine UCG combined with HFH in the treatment of uremic pruritus has a very good effect, Therefore, this study will systematically evaluate the clinical efficacy and safety of UCG combined with HFH and HFH alone in the treatment of uremic pruritus.Methods:Use computer to search English and Chinese databases, English databases include: PubMed, Web of Science, EMbase, The Cochrane Library. Chinese databases include: CNKI, CBM, WanFang Data and VIP databases, collecting the RCT on the clinical effectiveness and safety of UCG combined with HFH and HFH alone in the treatment of uremic pruritus. The retrieval time is from the beginning of each database to May 1, 2021. In order to improve the retrieval rate of the literature, the references cited in the included research are also collected and screened. Set Chinese and English as the search language. Two members of the research group independently collected, included and excluded the literatures. In case of disagreement, consulting the third party to assist in the judgment. For the literature with missing data, the original author should be contacted as far as possible to obtain complete data. Two evaluators evaluate the bias risk of included studies according to the Cochrane Handbook bias risk assessment tool for RCT. RevMan 5.3 software is used for statistical analysis and the forest plot is drawn to show the outcome indicators and funnel plot is drawn to show the publication bias.Results:This study evaluates the advantages and disadvantages of traditional Chinese medicine UCG combined with HFH and HFH alone in the treatment of uremic pruritus through the clinical effectiveness and safety-related indicators.Conclusion:This study will give a positive conclusion on the efficacy and safety of uremic clearance granule in the treatment of uremic pruritus, and the research results will be published in professional journals in the form of academic papers, thus benefiting more patients.Ethics and dissemination:This study belongs to meta-analysis and all data comes from academic papers published publicly in formal academic journals, so there are no ethical issues involved in this study and no ethical review or approval is required.OSF registration number:DOI 10.17605/OSF.IO/W8P5G.     

老年尿毒症患者脑血流动力学的分析

目的　探讨老年尿毒症患者脑血管血流动力学的变化及其影响因素。方法　采用经颅多谱勒超声 ,分别于血液透析 (血透 )和腹膜透析前后测量收缩期和舒张末期脑血管血流速度 (CABFV) ;监测血压变化 ;微盘测定法和放射免疫法分别检测血清一氧化氮 (NO)和内皮素 (ET)含量的变化 ,对CABFV与血压、血清NO和ET的关系进行分析。结果　老年尿毒症患者CABFV显著低于同龄正常老年人和中青年尿毒症患者 (收缩期 ,P <0 .0 1,舒张末期 ,P <0 .0 5 ) ;血透后CABFV在短期内进一步下降 (P <0 .0 1) ,腹膜透析前后CABFV没有显著变化 ;透析前后血压的变化没有统计学意义 ;血透可使血清NO和ET含量明显下降 (P <0 .0 0 1) ,但血透前血清NO和血透前后血清ET水平均明显高于正常老年人 (P <0 .0 0 1) ,而腹膜透析则对其没有影响 ;血透前收缩期CABFV的变化与血压和血清ET显著负相关 ,与血清NO显著正相关 (P <0 .0 0 1或 P <0 .0 1)。结论　老年尿毒症患者CABFV显著低于同龄正常老年人和中青年尿毒症患者 ,血透后短期内进一步下降 ;尿毒症患者血压、血清NO和ET水平均明显高于正常老年人 ;血透后血清NO和ET水平在一定时间内显著降低 ,而血压无明显改变 ;腹膜透析对上述指标无显著影响 ;血压、血清NO和ET的变化是导致老年尿毒症患者CA     

A case of systemic lupus erythematosus associated with hemolytic uremic syndrome

We report a case of systemic lupus erythematosus (SLE) associated with hemolytic uremic syndrome (HUS). The patient was a 13-year-old boy who had complained of nausea and diarrhea. Abnormal urinalysis, pancytopenia and renal dysfunction were revealed. The immunological studies showed an elevation of antinuclear antibody and anti-double-stranded DNA antibody titers with a low complement level. Renal biopsy specimens showed diffuse membranous glomerulonephritis with microthrombi in the glomerular capillary lumen. He was diagnosed as having SLE with HUS. Methylprednisolone pulse therapy was performed. Renal function, proteinuria and hematuria were gradually improved. Prednisolone and an immunosuppressive agent (mizoribine) were prescribedper os. In our case, diarrheal prodrome was present, so gastro-enteritis was suggested as the trigger of HUS, but the causal agent was not detected. HUS was considered to be an accelerator in the renal lesions of SLE. There have been few reported cases in children of SLE associated with HUS.     

A case of systemic lupus erythematosus associated with hemolytic uremic syndrome

Abstract

We report a case of systemic lupus erythematosus (SLE) associated with hemolytic uremic syndrome (HUS). The patient was a 13-year-old boy who had complained of nausea and diarrhea. Abnormal urinalysis, pancytopenia and renal dysfunction were revealed. The immunological studies showed an elevation of antinuclear antibody and anti-double-stranded DNA antibody titers with a low complement level. Renal biopsy specimens showed diffuse membranous glomerulonephritis with microthrombi in the glomerular capillary lumen. He was diagnosed as having SLE with HUS. Methylprednisolone pulse therapy was performed. Renal function, proteinuria and hematuria were gradually improved. Prednisolone and an immunosuppressive agent (mizoribine) were prescribed per os. In our case, diarrheal prodrome was present, so gastro-enteritis was suggested as the trigger of HUS, but the causal agent was not detected. HUS was considered to be an accelerator in the renal lesions of SLE. There have been few reported cases in children of SLE associated with HUS.     

Tei指数评价左心室射血分数正常的尿毒症患者的左心室功能

目的利用Tei指数评价左心室射血分数（left ventricular ejection fraction, LVEF）正常的尿毒症患者的左心功能,以了解其临床应用价值。方法选取80例LVEF正常的尿毒症患者设为尿毒症组,50名健康人设为对照组,使用Vivid7pro对两组进行检测。检测左心房内径（LAD）、左心室舒张期末内径（LVDd）、左心室收缩期末末内径（LVDs）、室间隔（IVS）及左心室后壁厚度（LVPW）、LVEF、左心室短轴缩短率（LVFS）、二尖瓣血流频谱E峰及A峰、E／A比值、左心室等容收缩时间（ICT）及等容舒张时间（IRT）、主动脉射血时间（ET）,并计算左心室Tei指数。结果尿毒症组左心房内径、左心室舒张期末内径、左心室收缩期末内径、室间隔、左心室后壁厚度均较对照组增大,差异有统计学意义（P均〈O．01）。尿毒症组的二尖瓣血流频谱E峰及A峰较对照组明显增大（P均〈0．05）、左心室等容舒张时间比对照组延长（P〈0．01）、主动脉射血时间比对照组缩短（P〈0．01）、Tei指数比对照组明显延长（0．50±0．18眠0．33±0．12,P〈0．叭）,差异有统计学意义;尿毒症组E／A比值、左心室等容收缩时间、LVEF及左心室短轴缩短率与对照组比较,差异无统计学意义（P均〉0．05）。结论测量Tei指数能比单纯LVEF更好地评价尿毒症患者的左心功能,而且方便、快捷、有效。