Rituximab (RTX) is the antiCD20 monoclonal antibody that has been used as the first-line therapy for primary membranous nephropathy (PMN) in recent years. However, the optimal dosing regimen and timing of RTX, or combination with other immunosuppressants, especially in patients with extremely high titers (> 1,000 RU/mL) of anti-PLA2R antibody (aPLA2R), are unclear at present. This report describes the case of a 70-year-old PMN patient with extremely high aPLA2R titer who failed to respond to very high doses of RTX. We also discuss the possible reasons for treatment failure.

Objective To explore the application value of urinary calprotectin in adult acute kidney injury（AKI） by observing urinary calprotectin concentration in adult AKI patients and healthy people. Methods Fifty patients with AKI（AKI group） and 30 healthy people（healthy control group） were selected to determine the indexes of urinary calprotectin, serum creatinine, blood urea nitrogen, urinary kidney injury molecule-1（KIM-1）, blood albumin and hemoglobin. General clinical data and laboratory indexes were compared between the two groups. ROC curve was used to analyze the predictive value of urinary calprotectin for adult AKI. Results Urinary calprotectin, urinary KIM-1, serum creatinine and blood urea nitrogen were higher in AKI group than in healthy control group（t=10.113, 9.152, 11.119 and 9.049 respectively; P＜0.001）. Urinary calprotectin was positively correlated with serum creatinine（r=0.794, P＜0.001）, urea nitrogen（r=0.462, P=0.001） and urinary KIM-1（r=0.409, P=0.003）, and was negatively correlated with serum albumin（r=-0.620,P=0.042） and hemoglobin（r=-0.289, P＜0.001） in AKI group. When the diagnostic limit of urinary calprotectin for adult AKI was set at 55.17ng/ml, the area under the ROC curve was 0.747（95% CI: 0. 641～0.853）,with the sensitivity of 62.0% and specificity of 90.0%. Conclusion Urinary calprotectin concentration was significantly increased, and was positively correlated with serum creatinine, blood urea nitrogen and urinary KIM-1 levels in adult AKI patients. The sensitivity and specificity of urinary calprotectin for the diagnosis of adult AKI are higher. Therefore, urinary calprotectin has an important clinical value in the prediction and evaluation of therapeutic effect and recovery process in adult AKI patients.

目的 通过观察成人急性肾损伤(acute?kidney?injury,AKI)患者和健康人群中尿钙卫蛋白(calprotectin,CLP)浓度水平,来探究尿CLP对成人AKI的预后评估价值.方法 选择潍坊市人民医院自2020年12月至2021年11月确诊为AKI的患者50例(AKI组)和健康体检中心的健康人群30名(健康对照组),检测两组研究对象的尿CLP、血肌酐、血尿素氮、尿肾损伤因子1(kid-ney?injury?molecule-1,KIM-1)、血白蛋白和血红蛋白等指标,同时收集一般资料,比较两组间上述检测指标的差异性.然后对上述AKI组患者随访90?d后进行分组,行肾脏替代治疗(renal?replace-ment?therapy,RRT)治疗的患者归为透析组,未行RRT治疗的患者归为非透析组;90?d后死亡的患者归为死亡组,未死亡的患者归为存活组,进行相关指标的比较,绘制受试者工作特征曲线(receiv-er?operating?characteristic?curve,ROC)曲线和AKI患者的生存曲线(乘积极限法),评价尿CLP在成人AKI预后中的价值.结果 AKI组患者尿CLP[(65.02?±?33.75)?μg/L比(37.85?±?17.33)?μg/L]、尿KIM-1[(52.21?±?30.91)ng/L比(30.86?±?15.38)ng/L]、血肌酐[(538.62?±?233.91)?μmol/L比(62.03?±14.27)?μmol/L]、血尿素氮[(20.85?±?9.38)?mmol/L比(5.26?±?1.02)?mmol/L]浓度较健康对照组增高.透析组患者的血肌酐[(654.53?±?218.68)?μmol/L比(478.91?±?221.49)?μmol/L]、尿CLP[(92.26?±?29.26)μg/L比(50.99?±?26.82)?μg/L]和尿KIM-1[(65.69?±?40.76)ng/L比(45.27?±?22.04)ng/L]水平较非透析组高,尿CLP预测成人AKI患者进行RRT治疗的诊断界值在76.92?μg/L时,ROC曲线下面积为0.850,敏感度和特异度分别为76.5％和87.9％.死亡组和存活组的尿CLP、血红蛋白、尿KIM-1、血尿素氮、收缩压和舒张压水平比较差异均无统计学意义.尿CLP预测成人AKI患者90?d病死率的曲线下面积为0.564,敏感度和特异度分别为76.5％和87.9％.透析组和非透析组90?d病死率差异无统计学意义(P>0.05).结论 成人AKI患者尿CLP水平较健康对照人群显著升高,尿CLP在预测AKI患者RRT需求方面显示出了一定程度的准确性,但是在预测AKI患者90?d病死率方面表现不佳.

zeste基因增强子同源物2(enhancer of zeste homolog 2,EZH2)是一种组蛋白赖氨酸甲基转移酶,可通过调控组蛋白H3在赖氨酸27位点的三甲基化(trimethylation of Lys27 in histone 3,H3K27me3),诱导靶基因沉默,在腹膜透析(peritoneal dialysis,PD)相关性腹膜纤维化过程中发挥重要作用.研究显示EZH2在腹膜纤维化过程中高表达,通过促进上皮细胞—间充质转化(epithelial-to-mesenchymal transition,EMT)、腹膜炎症和血管新生来促进腹膜纤维化的发生发展,抑制EZH2可抑制甚至部分逆转腹膜纤维化.深入研究EZH2有助于进一步明确腹膜纤维化的发病机制,并为腹膜纤维化的靶向治疗提供参考.

目的:探讨血清syndecan-1在成人急性肾损伤(acute kidney injury,AKI)诊断中的临床价值.方法:选取47例AKI患者(AKI组)和30例健康志愿者(对照组),检测两组血清syndecan-1、血清肌酐、血尿素氮、血清肾损伤因子-1(kidney injury molecule-1,KIM-1)、血白蛋白和血红蛋白等指标,同时收集人口统计学资料,比较两组指标的差异.采用ROC曲线分析血清syndecan-1对成人AKI的预测价值.结果:AKI组血清syndecan-1、KIM-1、血肌酐、尿素氮的水平明显高于对照组.AKI组血清syndecan-1和血清肌酐、血尿素氮、血KIM-1水平呈正相关,与血白蛋白、血红蛋白水平呈负相关.校正性别、年龄、血肌酐、尿素氮、收缩压、舒张压等因素后,血清syndecan-1仍与血清KIM-1和血肌酐水平呈正相关.血清syndecan-1诊断急性肾损伤的ROC曲线下面积为0.872,敏感度和特异度分别为78.7％和90％.结论:血清syn-decan-1浓度在成人AKI患者中明显升高,其诊断AKI的灵敏度和特异度较高,提示syndecan-1在诊断成人AKI中具有重要临床价值,可作为诊断早期AKI的敏感指标.

左乙拉西坦是一种广谱抗癫痫药物，主要用于部分性癫痫和全面性癫痫的单药治疗或辅助治疗。报道左乙拉西坦导致低钾血症1例，旨在提供低钾血症的病因分析、诊断、治疗经验，为临床用药安全提供参考。

维持性血液透析(maintenance hemodialysis,MHD)患者由于体内毒素蓄积、氧化应激和一些透析相关的因素,体内的单核巨噬细胞持续活化,机体存在低水平、持续的炎症状态,外周血清炎症因子水平升高,这种没有全身或局部显性的临床感染的状态称为微炎症状态.微炎症状态已被证实与MHD患者预后不良密切相关,C反应蛋白水平升高是其预后不良的独立危险因素.目前应用于改善微炎症状态的治疗方案较多,如他汀类药物、维生素C[1]、血管紧张素转化酶抑制剂(angiotensin-convert ing en-zyme inhibitor,ACEI)和血管紧张素受体拮抗剂(angiotensin receptor antagonist,ARB)类药物、抗抑郁药物、中药治疗、紫外线照射、抗氧化应激、营养干预、改善透析膜生物相容性等,但其疗效评估仍缺少大量临床数据的支持,行之有效的微炎症状态的治疗方案尚在不断探索中.

If the kidney suddenly loses its ability to remove waste, acute kidney injury (AKI) will occur that dangerous levels of waste may accumulate, and the chemical composition of the blood may become unbalanced. AKI usually develops rapidly within a few days and is very common in hospitalized patients, especially those in urgent need of intensive care. AKI can be fatal and requires serious treatment. However, it can be reversible. The purpose of this research was to investigate the effects of recombinant human erythropoietin (rhEPO) on the expression of nuclear factor E2-related factor 2 (Nuclear factor E2, Nrf2) and Heme oxygenase (HO-1) in rats AKI and its protective effects on the kidney. For this purpose, 40 SD rats were averagely and randomly divided into 4 groups: control group, sham operation group, model group, and rhEPO group. The rhEPO group was injected with 5% glucose mixed with rhEPO to form 3000 IU/ (kg/d) rhEPO. Except for the rhEPO group, three groups were injected with 5% glucose at the same dose level as the rhEPO group respectively. Before the third administration, the renal pedicle was clamped for 60 min and then perfused for 24 hours. Changes of Serum creatinine (Scr) and Urea nitrogen (BUN) of rats in each group were detected before and after modeling. Twenty-four hours after modeling, renal tissues of rats in each group were taken, and expressions of Nrf2 and HO-1 in renal tissues were detected by qRT-PCR and Western blot methods. There were no significant differences in Scr and BUN contents in the four groups before modeling (p> 0.05). There were no significant differences in Scr and BUN contents in the control group and sham operation group after modeling compared with those before modeling (p> 0.05). Expressions of Nrf2 and HO-1 in the rhEPO group were higher than those in the model group, the sham operation group and the control group (p< 0.05), while expressions of Nrf2 and HO-1 in model group were higher than those in sham operation group and control group (p< 0.05). There were no significant differences in expressions of Nrf2 and HO-1 between the sham operation group and the control group (p> 0.05). rhEPO can induce expressions of Nrf2 and HO-1 in AKI rats. RhEPO has a protective effect on the kidney, which may be related to expressions of Nrf2 and HO-1.

Expression of syndecan-1 (SDC-1) in rats with acute kidney injury and the protective effect of GM6001 on the kidney were investigated. Fifty SD rats were selected and randomly divided into control group (CG) (n=15), treatment control group (TCG) (n=10), module group (MG) (n=15) and treatment group (TG) (n=10). In TG, the model of acute renal injury (AKI) in rats was established after pretreatment of intraperitoneal injection of GM6001 one day before modeling. In MG, the same amount of saline was injected intraperitoneally one day before modeling and the same treatment was done on the day of modeling. In CG, the same amount of saline was injected intraperitoneally one day before modeling but the model was not made. In TCG, rats were pretreated with intraperitoneal injection of GM6001 one day before modeling but the model was not made. The contents of blood urea nitrogen (BUN) in serum, serum creatinine (SCR), uric acid (UA) and blood β2-microglobulin (β2-MG) were detected by ELISA. The content of SDC-1 in renal tissues was detected by qRT-PCR and western blotting. Expression of SDC-1 in renal tissue of 24 rats after modeling was lower than that of MG (P<0.050). SDC-1 expression was the highest in TG (P<0.05). Compared with before modeling, the contents of BUN, SCR, UA and β2-MG in MG and TG increased (P<0.05). After modeling, the contents of serum BUN, SCR, UA and β2-MG in TG were significantly lower than those in MG (P<0.05). The levels of SDC-1 in renal tissue of rats with acute kidney injury increased. After GM6001 treatment, SDC-1 levels can be improved and has a certain protective effect on the kidneys.

目的 观察梗阻性急性肾损伤(AKI)患者血清血红素加氧酶1(HO-1)的水平变化,并探讨其临床意义.方法 选取33例梗阻性AKI患者(AKI组)及30例健康体检者(健康对照组),采用酶联免疫吸附法检测两组血清HO-1、肾损伤因子(KIM-1)等指标.采用Spearman相关分析血清HO-1、KIM-1水平的相关性;绘制受试者工作特征(ROC)曲线评价HO-1对梗阻性AKI的诊断价值;用二分类Logistic回归分析梗阻性AKI发病的影响因素.结果 AKI组血清HO-1、KIM-1水平高于健康对照组(P均＜0.01).AKI组血清HO-1水平与血清KIM-1水平呈正相关(r=0.596,P＜0.01).HO-1对AKI的诊断界值为0.60 pg/mL,其ROC曲线下面积为0.869,敏感度和特异度分别为81.8％、77.8％.血清HO-1、KIM-1水平升高是梗阻性AKI发生的危险因素.结论 梗阻性AKI患者血清HO-1水平升高,其诊断梗阻性AKI的灵敏度和特异度较高,HO-1水平升高的患者易发生梗阻性AKI.

目的:评估尿血红素加氧酶-1(heme oxygenase-1,HO-1)和尿肾损伤分子-1(kidney Injury molecule-1,KIM-1)水平对急性肾损伤的预测价值.方法:筛选2017年08月～2018年08月期间于潍坊市人民医院住院的确诊急性肾损伤(acute kidney injury,AKI)患者38例及慢性肾脏病组30例,健康对照组30例,采用受试者工作特征曲线(ROC曲线)评价观察指标的预测价值.结果:急性肾损伤组在确诊急性肾损伤后6h的尿HO-1、尿KIM-1、血清尿素氮、血清肌酐、血清尿酸均高于健康对照组,差异均有统计学意义(P＜0.05).确诊急性肾损伤后6h的尿HO-1高于慢性肾脏病组,差异有统计学意义(P＜0.05).而慢性肾脏病组的尿HO-1水平与健康对照组相比较,差异无统计学意义(P＞0.05).确诊急性肾损伤组6h内的尿HO-1和尿KIM-1ROC曲线下面积分别为0.804和0.802.当急性肾损伤组6h内尿HO-1为0.885 pg/ml时,敏感度和特异度分别为71.1％和86.7％;当急性肾损伤组6h内尿KIM-1为0.8 ng/ml时,敏感度和特异度分别为65.8％和86.7％.结论:尿HO-1及尿KIM-1均是预测AKI的良好指标.

目的 探讨成人尿蛋白聚糖-1(syndecan-1)和急性肾损伤(AKI)的关系.方法 选取47例成人AKI患者(AKI组)及30例健康体检者(对照组),检测两组患者的尿syndecan-1、血肌酐、尿素氮、血红蛋白、血白蛋白等指标,同时收集人口统计学资料,比较两组各指标的差异.绘制ROC曲线,探讨尿syndecan-1对成人AKI的预测价值.结果 AKI组患者尿syndecan-1水平(1264.32±683.68)μg/L明显高于对照组(807.43±285.71)μg/L(P=0.001).AKI组患者尿syndecan-1和血肌酐水平呈正相关(Pearson r=0.476,P＜0.01),与血白蛋白、血红蛋白水平呈负相关(分别为Pearson r=-0.322,P=0.004;Pearson r=-0.300,P=0.008).尿syndecan-1诊断AKI的ROC曲线下面积为0.707,敏感度和特异度分别为63.8％和73.3％.结论 成人AKI患者尿syndecan-1明显升高,提示其对成人AKI可能具有诊断价值.

As one of the most important water-soluble non-enzymatic antioxidants,vitamin C consists of ascorbic acid and its oxidized form,dehydroascorbic acid.Maintenance hemodialysis（MHD）patients have a generally lower plasma vitamin C level compared with general population.Moreover,dialysis patients also exhibit a low plasma vitamin C level,which is largely related with increased inflammation,refractory anemia and oxidative stress.In this review,we described,in great detail,the vitamin C deficiency in MHD patients and its effects on anti-oxidation,anti-inflammation,pro-oxidation and secondary hyperparathyroidism.In addition,we described the possible potential value of vitamin C in anemia,and the side effects of over-doses of vitamin C supplementation in this particular population.In summary,MHD patients may benefit from vitamin C administration.However,further research should be carried out to confirm its potential beneficial effects,optimal dosage and side effects from vitamin C supplementation.

Objective Toexoloretheimoactofheoarinonolasmamyelooeroxidase(MPO)levelsduringtheorocess ofarteriovenousfistulaformationinuremicoatients.Methods FromJanuary2011toJune2013,inthehematodialysiscenterof Weifang Peoole's Hosoital,the levels of olasma MPO and serum high-sensitivity C-reactive orotein( hs-CRP)were deter-mined by enzyme-linked immunosorbent assay( ELISA)and immunoturbidimetry( ITM)in 31 uremic oatients who had arterio-venousfistulaformationforthefirsttimebeforeheoarininjection,athours0.5,2.0after.Results Therewassignificant difference among olasma MPO levels before heoarin,at hours 0. 5,2. 0 after heoarin(F =11. 654,P <0. 05). MPO was higher at 0. 5 h after heoarin than before(P<0. 05),there was no difference between MPO levels before heoarin and at 2. 0 h after(P>0. 05),lower at 2. 0 h after heoarin than at 0. 5 h(P<0. 05). There was no difference among serum hs-CRP lev-elsbeforeheoarin,athours0.5,2.0after(F=0.074,P>0.05).Conclusion Inuremicoatients,olasmaMPOlevelin-creases transiently during the orocess of arteriovenous fistula formation,but hs-CRP level does not change obviously,which may be caused by heoarin stimulating vessel walls to release MPO.

Accelerated atherosclerosis is the major cause of mortality in maintenance hemodialysis (MHD) patients, and endothelial injury associated with MHD might contribute strongly to pathogenesis. The current study was designed to explore possible associations between circulating endothelial cells (CECs) and intima-media thickness of common carotid artery (CCA-IMT) as an indicator of carotid atherosclerosis. Sixty-two MHD patients and 26 age- and sex-matched healthy volunteers were recruited. The number of CECs was determined in peripheral blood using multiparametric flow cytometry. CCA-IMT and presence of plaques in the common carotid arteries were assessed with ultrasound. Laboratory tests results and the demographics were recorded. The finding indicated that numbers of CECs were higher in patients before hemodialysis (predialysis) compared with numbers in controls ( P = 0.045). CCA-IMT was also significantly higher in patients than in controls ( P < 0.01). A positive relationship was observed between predialysis CECs numbers and CCA-IMT ( P < 0.01) in MHD patients. In multiple linear regression analysis, the relationship between the predialysis CECs level and CCA-IMT remained the same even if adjusting for confounding effects. Accordingly, the investigation indicates that the CECs level is positively associated with CCA-IMT in our hemodialysis patients. CECs might be an important marker to the severity of carotid atherosclerosis in MHD patients.

Endothelial dysfunction may play a crucial role in initiation of the pathogenesis of vascular disease and atherosclerosis. The identification and quantification of circulating endothelial cells (CEC) have been developed as a novel marker of endothelial function. We describe, in great detail, mechanisms of endothelial dysfunction and CEC detachment. We also review the relationship between numbers of CEC and disease severity and response to treatment. In addition, we describe the possible clinical use of CEC in chronic kidney disease (CKD) and kidney transplantation. In summary, CEC have been developed as a novel approach to assess the endothelial damage. Measurement of the CEC level would provide an important diagnostic and prognostic value on the endothelium status and the long-term outcome of vascular dysfunction.

Objective To explore possible associations between osteopontin(OPN) and intact parathyroid hormone(iPTH),to investigate effects of them on the progression of carotid artery calcification in patients receiving long-term hemodialysis.Methods Forty-eight maintenance hemodialysis (MHD) patients and 28 age-and sex-matched healthy volunteers were recruited.The concentration of OPN in peripheral blood was determined by enzyme linked immunosorbent assay (ELISA).Levels of iPTH and presence of plaques in the common carotid arteries were also measured.The demographics were recorded.Results Compared with controls,levels of OPN[(137.4±80.8) ng/L vs (31.6±6.7) ng/L,P ＜ 0.01] and iPTH[(456.4±326.4) ng/L vs (66.9±19.3) ng/L,P ＜ 0.01] were higher in MHD patients before hemodialysis,the numbers of calcific plaques in the common carotid arteries were increased in MHD patients (P ＜ 0.01).There was a positive correlation between pre-dialysis OPN levels and iPTH levels (r =0.620,P ＜ 0.01) in MHD patients.Higher levels of OPN and iPTH correlated with greater numbers of calcific plaques in the common carotid arteries after division into three subgroups of MHD patients based on calcific plaques.In multiple linear regression analysis,the correlation between the pre-dialysis OPN and iPTH levels remained the same even if adjusting for confounding effects[β =0.468,95％C1 (0.036,0.195),t =2.936,P =0.005].Conclusion OPN level is positively correlated with iPTH level in hemodialysis patients,which suggesting that both of them play important roles in the progression of carotid artery calcification.

BACKGROUND:Both vitamin C deficiency and inflammation are prevalent in maintenance hemodialysis (MHD) patients. In this study, we aimed to elucidate the effect of oral vitamin C supplementation on inflammatory status in MHD patients with low vitamin C level and high hypersensitive C-reactive protein (hs-CRP) level.METHODS:A total of 128 patients were recruited in our present study. Patients were divided into two groups. In group 1 (n = 67), patients were orally administered with 200 mg/day vitamin C in the first 3 months, and then the vitamin C supplementation was withdrawn in the next 3 months. In group 2 (n = 61), patients were not given vitamin C in the first 3 months, and then they were orally administered with 200 mg/day in the next 3 months. Levels of hs-CRP, prealbumin, albumin and hemoglobin as well as the EPO resistance index (ERI) were determined at the baseline and every 3 months throughout the study. Plasma vitamin C level was determined by high-performance liquid chromatography with UV detection.RESULTS:Among the 128 patients, 28 of them dropped out of the study before completion. Consequently, a total of 100 patients (group 1: n = 48; group 2: n = 52) were included in the final analysis. At the baseline, the plasma vitamin C level of all patients was less than 4 μg/mL. However, this proportion was decreased to 20% after the vitamin C supplementation for 3 months. Compared with patients without the vitamin C supplementation, a decreased level of hs-CRP and an increased level of prealbumin were induced by the vitamin C supplementation for 3 months in both groups. However, levels of these biomarkers returned to their original state after the supplementation was withdrawn. Same beneficial effects on plasma albumin, hemoglobin and ERI response to vitamin C supplementation were observed in the two groups without statistical significance.CONCLUSIONS:The inflammatory status in MHD patients with plasma vitamin C deficiency and high levels of inflammatory markers could be partially improved by long-term oral administration of small doses of vitamin C.TRIAL REGISTRATION:The clinical trial number: NCT01356433.

Resistive switching (RS) phenomenon in the HfO2 dielectric has been indirectly observed at device level in previous studies using metal-insulator-metal structures, but its origin remains unclear. In this work, using the enhanced conductive atomic force microscope (ECAFM), we have been able to obtain in situ direct observation of RS with nanometric resolution. The ECAFM measurements reveal that the conductive filaments exhibiting the RS are primarily formed at the grain boundaries, which were shown exhibiting especially low breakdown voltage due to their intrinsic high density of the oxygen vacancies.

ABSTRACT Aim: We designed a cross‐sectional study to investigate plasma vitamin C level in patients who underwent maintenance haemodialysis (MHD) and continuous ambulatory peritoneal dialysis (CAPD) to explore whether there is a difference in vitamin C deficiency between MHD patients and CAPD patients. Methods: This investigation included 382 dialysis patients without vitamin C supplement before the study. Demographic characteristics, laboratory tests, ascorbic acid and total plasma vitamin C level were measured. A linear regression model was built to explore the association between vitamin C deficiency and dialysis modalities after adjusting for age, dialysis vintage, gender, Charlson index, modality of dialysis and hsCRP. Results: The range of plasma vitamin C level was from 0.48 µg/mL to 31.16 µg/mL. 35.9% ( n = 137) patients had severe vitamin C deficiency (<2 µg/mL). Plasma vitamin C level was inversely associated with age and dialysis vintage. After age and dialysis vintage were adjusted, vitamin C deficiency was associated with MHD. R square for model fitting was relatively low, which implied that there were other vitamin C influencing factors not included in the model. Conclusions: Vitamin C deficiency is common in dialysis patients, especially in patients treated with MHD.