BACKGROUND & AIMS: :Contrast-induced nephropathy is an iatrogenic disease caused by the administration of iodinated contrast material to certain at-risk patients. The clinical features include renal failure, with oliguria, anuria, and electrolyte derangements. Contrast-induced nephropathy can prolong hospitalization, result in greater morbidity and mortality, and increase patients' costs. A variety of preventive and treatment strategies exist, including use of alternative imaging. Critical care nurses need to understand the nephropathy and the patients at risk and to develop a familiarity with prevention, treatment, and outcome.

背景与目标： 造影剂肾病是一种医源性疾病，是由某些风险患者服用碘化造影剂引起的。临床特征包括肾功能衰竭，少尿，无尿和电解质紊乱。造影剂诱发的肾病会延长住院时间，导致更高的发病率和死亡率，并增加患者的费用。存在多种预防和治疗策略，包括使用替代成像。重症监护护士需要了解肾病和处于危险中的患者，并熟悉预防，治疗和结局。

BACKGROUND & AIMS: :M-type phospholipase A2 receptor (PLA2R) is the major target antigen in primary membranous nephropathy (PMN). Previous studies have evaluated the diagnostic value of serum anti-PLA2R antibody. However, the correlation of serum anti-PLA2R antibody and glomerular PLA2R deposition, and their association with clinical characteristics need to be further evaluated.A total of 136 patients were involved as inception group because serum anti-PLA2R antibody and glomerular PLA2R antigen were simultaneously measured. We examined serum anti-PLA2R antibody by ELISA and glomerular PLA2R deposition by immunofluorescence assay.Positive serum anti-PLA2R antibody and glomerular PLA2R deposition were seen in 58.8% (80/136) and 95.6% (130/136) patients, respectively (P < .001). Proteinuria, serum total protein, serum albumin, serum creatinine, and estimated glomerular filtration rate (eGFR) had significant differences between patients with serum anti-PLA2R antibody and those without. Serum anti-PLA2R antibody levels were correlated with serum albumin, serum creatinine, eGFR, and proteinuria. Glomerular PLA2R deposition intensities were weakly correlated with proteinuria. Unexpectedly, there was a positive correlation rather than a negative correlation between glomerular PLA2R deposition intensity and eGFR.In conclusion, serum anti-PLA2R antibody is more closely correlated with disease activity and renal function than glomerular PLA2R deposition.

背景与目标： ：M型磷脂酶A2受体（PLA2R）是原发性膜性肾病（PMN）的主要靶抗原。先前的研究已经评估了血清抗PLA2R抗体的诊断价值。然而，血清抗PLA2R抗体与肾小球PLA2R沉积的相关性及其与临床特征的相关性需要进一步评估。由于同时检测了血清抗PLA2R抗体和肾小球PLA2R抗原，因此共有136例患者入组。 。我们通过ELISA检测了血清抗PLA2R抗体，并通过免疫荧光法检测了肾小球PLA2R沉积。分别在58.8％（80/136）和95.6％（130/136）患者中观察到阳性血清抗PLA2R抗体和肾小球PLA2R沉积（P <.001）。蛋白尿，血清总蛋白，血清白蛋白，血清肌酐和估计的肾小球滤过率（eGFR）在有血清抗PLA2R抗体的患者和没有血清抗PLA2R抗体的患者之间有显着差异。血清抗PLA2R抗体水平与血清​​白蛋白，血清肌酐，eGFR和蛋白尿相关。肾小球PLA2R沉积强度与蛋白尿弱相关。出乎意料的是，肾小球PLA2R沉积强度与eGFR之间呈正相关而非负相关。总之，血清抗PLA2R抗体与肾小球PLA2R沉积与疾病活动性和肾功能之间的相关性更高。

BACKGROUND & AIMS: AIMS/HYPOTHESIS:Type 2 diabetes is a chronic metabolic disorder associated with devastating microvascular complications. Genome-wide association studies have identified more than 60 genetic variants associated with type 2 diabetes and/or glucose and insulin traits, but their role in the progression of diabetes is not established. The aim of this study was to explore whether these variants were also associated with the development of nephropathy in patients with type 2 diabetes. METHODS:We studied 28 genetic variants in 2,229 patients with type 2 diabetes from the local Malmö Scania Diabetes Registry (SDR) published during 2007-2010. Diabetic nephropathy (DN) was defined as micro- or macroalbuminuria and/or end-stage renal disease. Estimated glomerular filtration rate (eGFR) was assessed using the MDRD-4 formula. Replication genotyping of rs1531343 was performed in diabetic (Steno type 2 diabetes [n = 345], Genetics of Diabetes Audit and Research in Tayside Scotland [Go-DARTS] [n = 784]) and non-diabetic (Malmö Preventive Project [n = 2,523], Botnia study [n = 2,247]) cohorts. RESULTS:In the SDR, HMGA2 single-nucleotide polymorphism rs1531343 was associated with DN (OR 1.50, 95% CI 1.20, 1.87, p = 0.00035). In the combined analysis totalling 3,358 patients with type 2 diabetes (n = 1,233 cases, n = 2,125 controls), carriers of the C-allele had a 1.45-fold increased risk of developing nephropathy (95% CI 1.20, 1.75, p = 0.00010). Furthermore, the risk C-allele was associated with lower eGFR in patients with type 2 diabetes (n = 2,499, β ± SEM, -3.7 ± 1.2 ml/min, p = 0.002) and also in non-diabetic individuals (n = 17,602, β ± SEM, -0.008 ± 0.003 ml/min (log( e )), p = 0.006). CONCLUSIONS/INTERPRETATION:These data demonstrate that the HMGA2 variant seems to be associated with increased risk of developing nephropathy in patients with type 2 diabetes and lower eGFR in both diabetic and non-diabetic individuals and could thus be a common denominator in the pathogenesis of type 2 diabetes and kidney complications.

背景与目标： 目的/假设：2型糖尿病是与破坏性微血管并发症相关的慢性代谢性疾病。全基因组关联研究已鉴定出与2型糖尿病和/或葡萄糖和胰岛素性状相关的60多种遗传变异，但尚未确定它们在糖尿病进展中的作用。这项研究的目的是探讨这些变异是否也与2型糖尿病患者的肾病发展有关。
方法：我们研究了2007年至2010年间发表的2 229例2型糖尿病患者的28种遗传变异，这些变异来自当地的马尔默斯堪尼亚糖尿病登记处（SDR）。糖尿病性肾病（DN）被定义为微蛋白尿或巨蛋白尿和/或晚期肾病。使用MDRD-4公式评估估计的肾小球滤过率（eGFR）。 rs1531343的复制基因分型是在糖尿病（Steno 2型糖尿病[n = 345]，Tayside Scotland糖尿病的遗传学研究和研究[Go-DARTS] [n = 784]）和非糖尿病（Malmö预防项目[n == 2,523]，Botnia研究[n = 2,247]队列。
结果：在SDR中，HMGA2单核苷酸多态性rs1531343与DN相关（OR 1.50，95％CI 1.20，1.87，p = 0.00035）。在总共3358名2型糖尿病患者的综合分析中（n = 1,233例，n = 2,125对照），C-等位基因携带者患肾病的风险增加了1.45倍（95％CI 1.20，1.75，p = 0.00010 ）。此外，高风险C等位基因与2型糖尿病患者的eGFR较低有关（n = 2,499，β±SEM，-3.7±1.2 ml / min，p = 0.002），在非糖尿病患者中（n = 17,602） ，β±SEM，-0.008±0.003 ml / min（log（e）），p = 0.006）。
结论/解释：这些数据表明，HMGA2变异似乎与2型糖尿病患者发生肾病的风险增加以及糖尿病和非糖尿病患者的eGFR降低有关，因此可能是2型糖尿病发病机制的共同指标2糖尿病和肾脏并发症。

BACKGROUND & AIMS: :Dermatophagoides farinae-, ovalbumin- and lactalbumin-specific IgG, IgG1, IgG4, IgA and IgM were evaluated in 161 healthy children [Group 1], 84 children with bronchial asthma and/or allergic rhinitis but without atopic dermatitis [Group 2], and 54 children with atopic dermatitis but without bronchial asthma and allergic rhinitis [Group 3]. We also studied D. farinae-, egg-white-, and milk-specific IgE of children with allergic diseases. D. farinae-specific IgG, IgG1, IgG4 and IgA in Groups 2 and 3 increased until 5 years of age and thereafter they remained constant. After 2 years of age, D. farinae-specific IgG, IgG1, IgG4 and IgA in Group 2 were higher than those in Groups 1 and 3. Ovalbumin- and lactalbumin-specific IgG, IgG1, IgG4 and IgA in Groups 2 and 3 increased until 1 year of age and thereafter decreased. Until 1 year of age, ovalbumin- and lactalbumin-specific IgG, IgG1 and IgG4 in Groups 3 were higher than those in Groups 1 and 2. D. farinae-, ovalbumin- and lactalbumin-specific IgM were constant in all ages of all groups. These results suggest that atopic dermatitis in young children is related to food-specific immunoglobulins and that respiratory allergic diseases in older children is related to D. farinae-specific immunoglobulins.

背景与目标： ：在161名健康儿童（第1组），84例支气管哮喘和/或过敏性鼻炎但无特应性皮炎的儿童（第2组）中评估了粉状皮癣，卵白蛋白和乳白蛋白特异性IgG，IgG1，IgG4，IgA和IgM。 54例患特应性皮炎但无支气管哮喘和过敏性鼻炎的儿童[3组]。我们还研究了患有过敏性疾病的儿童的D. farinae，蛋清和牛奶特异性IgE。第2组和第3组中的D. farinae特异性IgG，IgG1，IgG4和IgA升高至5岁，此后保持恒定。 2岁后，第2组的粉虱D. farinae特异性IgG，IgG1，IgG4和IgA高于第1和3组。第2和第3组的卵白蛋白和乳白蛋白特异性IgG，IgG1，IgG4和IgA增加。直到1岁，此后才减少。直到1岁之前，第3组中卵白蛋白和乳白蛋白特异性IgG，IgG1和IgG4高于第1组和第2组。粉虱，卵白蛋白和乳白蛋白特异性IgM在所有组的所有年龄中均保持不变。 。这些结果表明，幼儿的特应性皮炎与食物特异性免疫球蛋白有关，而年龄较大的儿童的呼吸道过敏性疾病与粉虱（D. farinae）特异性免疫球蛋白有关。

BACKGROUND & AIMS: OBJECTIVE:Statins reduce inflammation and risk of myocardial infarction (MI). Because the myeloid IgA Fc receptor encoded by FCAR mediates inflammation, we hypothesized that the FCAR Asp92Asn polymorphism is associated with risk of MI and that this risk would be modified by pravastatin. METHODS AND RESULTS:In the placebo arm of the Cholesterol and Recurrent Events (CARE) study, male carriers of the 92Asn allele had an adjusted hazard ratio for incident MI of 1.68 (95% CI 1.10 to 2.57); relative risk reduction by pravastatin was 69% in carriers and 12% in noncarriers (P(interaction)=0.007). In the placebo arm of the all-male West of Scotland Coronary Prevention Study (WOSCOPS), carriers had an adjusted odds ratio for incident coronary heart disease (CHD) of 1.46 (90% CI 1.05 to 2.03); for pravastatin compared with placebo treatment, the adjusted odds ratios were 0.55 (95% CI 0.32 to 0.93) in carriers and 0.65 (95% CI 0.51 to 0.83) in noncarriers (P(interaction)=0.55). CONCLUSIONS:Carriers of 92Asn had increased risk of MI in CARE and increased odds of CHD in WOSCOPS. Pravastatin significantly reduced risk in carriers in both CARE and WOSCOPS. A genotype by treatment interaction was observed in CARE but not in WOSCOPS.

背景与目标： 目的：他汀类药物可减少炎症和心肌梗塞（MI）的风险。因为由FCAR编码的髓样IgA Fc受体介导炎症，所以我们假设FCAR Asp92Asn多态性与MI的风险有关，并且这种风险将被普伐他汀改变。
方法和结果：在胆固醇和复发性事件（CARE）研究的安慰剂组中，92Asn等位基因的男性携带者调整后的MI危险比为1.68（95％CI 1.10至2.57）。普伐他汀的相对危险度降低在携带者中为69％，在非携带者中为12％（P（相互作用）= 0.007）。在全男性西苏格兰冠状动脉预防研究（WOSCOPS）的安慰剂组中，携带者的冠状动脉心脏病（CHD）调整后优势比为1.46（90％CI为1.05至2.03）。对于普伐他汀，与安慰剂治疗相比，调整后的优势比在载体中为0.55（95％CI 0.32至0.93），在非载体中为0.65（95％CI 0.51至0.83）（P（相互作用）= 0.55）。
结论：92Asn携带者在CARE中发生MI的风险增加，在WOSCOPS中发生CHD的几率增加。普伐他汀可显着降低CARE和WOSCOPS中携带者的风险。在CARE中观察到通过治疗相互作用产生的基因型，但在WOSCOPS中未观察到。

BACKGROUND & AIMS: :Chronic hyperglycaemia in diabetes leads to the overproduction of free radicals and evidence is increasing that these contribute to the development of diabetic nephropathy. Among the spices, turmeric (Curcuma longa) is used as a flavouring and colouring agent in the indian diet every day and is known to possess anti-oxidant properties. The present study was designed to examine the effect of curcumin, a yellow pigment of turmeric, on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats. Four weeks after STZ injection, rats were divided into four groups, namely control rats, diabetic rats and diabetic rats treated with curcumin (15 and 30 mg/kg, p.o.) for 2 weeks. Renal function was assessed by creatinine, blood urea nitrogen, creatinine and urea clearance and urine albumin excretion. Oxidative stress was measured by renal malonaldehyde, reduced glutathione and the anti-oxidant enzymes superoxide dismutase and catalase. Streptozotocin-injected rats showed significant increases in blood glucose, polyuria and a decrease in bodyweight compared with age-matched control rats. After 6 weeks, diabetic rats also exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance and proteinuria, along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key anti-oxidant enzymes. Chronic treatment with curcumin significantly attenuated both renal dysfunction and oxidative stress in diabetic rats. These results provide confirmatory evidence of oxidative stress in diabetic nephropathy and point towards the possible anti-oxidative mechanism being responsible for the nephroprotective action of curcumin.

背景与目标： ：糖尿病中的慢性高血糖症导致自由基的过度产生，并且越来越多的证据表明这些自由基有助于糖尿病性肾病的发展。在香料中，姜黄（姜黄）每天在印度饮食中用作调味剂和着色剂，并且已知具有抗氧化特性。本研究旨在检查姜黄素（一种姜黄黄色素）对链脲佐菌素（STZ）诱导的糖尿病大鼠肾功能和氧化应激的影响。在大鼠中通过腹膜内单次注射STZ（65 mg / kg）诱发糖尿病。注射STZ后四周，将大鼠分为四组，即对照大鼠，糖尿病大鼠和经姜黄素（15和30 mg / kg，口服）治疗2周的糖尿病大鼠。通过肌酐，血液尿素氮，肌酐和尿素清除率以及尿白蛋白排泄评估肾功能。通过肾脏丙二醛，还原型谷胱甘肽和抗氧化酶超氧化物歧化酶和过氧化氢酶来测定氧化应激。与年龄相称的对照大鼠相比，注射链脲佐菌素的大鼠显示血糖，多尿明显增加，体重下降。 6周后，糖尿病大鼠还表现出肾功能不全，这由肌酐和尿素清除率降低以及蛋白尿以及氧化应激显着增加所证实，氧化应激由脂质过氧化作用和关键抗氧化酶的活性决定。姜黄素的慢性治疗可显着减轻糖尿病大鼠的肾功能不全和氧化应激。这些结果提供了糖尿病性肾病中氧化应激的确证证据，并指出可能的抗氧化机制负责姜黄素的肾保护作用。

BACKGROUND & AIMS: :Pyodermatitis-pyostomatitis vegetans (PPV) constitutes an inflammatory mucocutaneous dermatosis that is associated with inflammatory bowel disease. Clinically, PPV appears as pustules on mucosal surfaces and as vegetating exudative plaques on intertriginous surfaces. It is typically a clinical diagnosis supported by histological findings. Microscopic findings include epidermal hyperplasia, focal acantholysis, and a dense mixed inflammatory infiltrate with intraepithelial and subepithelial eosinophilic microabscesses. In the recent literature, immunofluorescence has been thought to be negative in PPV or, if positive, an aberrant finding. Herein, we report 2 cases of PPV associated with inflammatory bowel disease, which display intercellular IgA deposits. Although these cases may represent isolated epiphenomena, it is possible that the paucity of PPV cases with immunofluorescent studies hitherto has led to an oversight of an interesting association between intercellular IgA and PPV.

背景与目标： ：脓皮炎-化脓性植物炎（PPV）构成了与炎症性肠病有关的炎症性粘膜皮肤性皮肤病。临床上，PPV在粘膜表面以脓疱的形式出现，在三叉间表面以植物性渗出性斑块出现。通常是组织学检查结果支持的临床诊断。显微镜下的发现包括表皮增生，局灶性棘层松解以及上皮内和上皮下嗜酸性微脓肿的致密混合炎性浸润。在最近的文献中，免疫荧光在PPV中被认为是阴性的，或者，如果阳性，则是异常的发现。在此，我们报告了2例与炎症性肠病相关的PPV病例，这些病例表现出细胞间IgA沉积物。尽管这些病例可能代表了孤立的现象，但迄今为止对PPV病例进行免疫荧光研究的可能性很低，导致对细胞间IgA与PPV之间有趣关系的疏忽。

BACKGROUND & AIMS: :Chronic exposure to high glucose leads to diabetic nephropathy characterized by increased mesangial matrix protein (e.g., collagen) accumulation. Altered cell signaling and gene expression accompanied by oxidative stress have been documented. The contribution of the tyrosine kinase, c-Src (Src), which is sensitive to oxidative stress, was examined. Cultured rat mesangial cells were exposed to high glucose (25 mmol/L) in the presence and absence of Src inhibitors (PP2, SU6656), Src small interfering RNA (siRNA), and the tumor necrosis factor-α-converting enzyme (TACE) inhibitor, TAPI-2. Src was investigated in vivo by administration of PP2 to streptozotocin (STZ)-induced diabetic DBA2/J mice. High glucose stimulated Src, TACE, epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK1/2, p38), and collagen IV accumulation in mesangial cells. PP2 and SU6656 blocked high glucose-stimulated phosphorylation of Src Tyr-416, EGFR, and MAPKs. These inhibitors and Src knockdown by siRNA, as well as TAPI-2, also abrogated high glucose-induced phosphorylation of these targets and collagen IV accumulation. In STZ-diabetic mice, albuminuria, increased Src pTyr-416, TACE activation, ERK and EGFR phosphorylation, glomerular collagen accumulation, and podocyte loss were inhibited by PP2. These data indicate a role for Src in a high glucose-Src-TACE-heparin-binding epidermal growth factor-EGFR-MAPK-signaling pathway to collagen accumulation. Thus, Src may provide a novel therapeutic target for diabetic nephropathy.

背景与目标： ：长期暴露于高葡萄糖会导致糖尿病肾病，其特征是肾小球系膜基质蛋白（例如胶原蛋白）蓄积增加。已经记录了改变的细胞信号传导和基因表达并伴有氧化应激。检查了对氧化应激敏感的酪氨酸激酶c-Src（Src）的贡献。在存在和不存在Src抑制剂（PP2，SU6656），Src小干扰RNA（siRNA）和肿瘤坏死因子-α转化酶（TACE）的情况下，将培养的大鼠系膜细胞暴露于高葡萄糖（25 mmol / L）抑制剂，TAPI-2。通过对链脲佐菌素（STZ）诱导的糖尿病DBA2 / J小鼠施用PP2在体内研究了Src。高葡萄糖刺激的Src，TACE，表皮生长因子受体（EGFR），促分裂原激活的蛋白激酶（MAPK），细胞外信号调节激酶（ERK1 / 2，p38）和胶原IV在肾小球膜细胞中的蓄积。 PP2和SU6656阻止了Src Tyr-416，EGFR和MAPK的高葡萄糖刺激磷酸化。这些抑制剂和siRNA以及SAPI敲除的Src敲除也废除了这些靶标的高葡萄糖诱导的磷酸化和胶原IV的积累。在STZ糖尿病小鼠中，白蛋白尿，Src pTyr-416升高，TACE活化，ERK和EGFR磷酸化，肾小球胶原蛋白积聚和足细胞丢失均被PP2抑制。这些数据表明Src在高葡萄糖-Src-TACE-肝素结合表皮生长因子-EGFR-MAPK信号转导至胶原积累中的作用。因此，Src可以为糖尿病性肾病提供新的治疗靶标。

BACKGROUND & AIMS: :BK virus nephropathy (BKVN) is increasingly recognized as a major cause of renal allograft failure. Recent reports demonstrate that prompt reduction of immunosuppression upon detection of persistent viremia can be associated with resolution of viremia, with minimal risk of acute rejection (AR). However, these experiences in general have occurred in centers with low baseline risks of AR. It is possible that a finer balance between overimmunosuppression and the risk of AR may exist in centers that routinely transplant patients with higher risk of AR. Thus the risk/benefit of this strategy may be altered in these centers. We report a case of antibody-mediated rejection that followed reduction of immunosuppression for BKVN diagnosed more than 3 months after the onset of viremia. This rejection episode resulted in a greater decrease in graft function than the initial BKVN episode. Issues relevant to the management of these patients are discussed, including the need for improved immune monitoring assays to determine more accurately the balance between infection and rejection.

背景与目标： ：BK病毒性肾病（BKVN）被越来越多地认为是同种异体肾功能衰竭的主要原因。最近的报道表明，检测到持续的病毒血症后，免疫抑制的迅速降低可与病毒血症的消退相关，而急性排斥反应（AR）的风险最小。但是，这些经验通常发生在AR基线风险较低的中心。在常规移植AR风险较高的患者的中心中，过度免疫抑制和AR风险之间可能存在更好的平衡。因此，在这些中心可以改变这种策略的风险/利益。我们报告了一例抗体介导的排斥反应，随后在病毒血症发作后3个月内诊断为BKVN的免疫抑制降低。与最初的BKVN发作相比，该排斥发作导致移植物功能的下降更大。讨论了与这些患者的治疗有关的问题，包括需要改进免疫监测方法以更准确地确定感染和排斥反应之间的平衡。

BACKGROUND & AIMS: :Crystalized deposits of monosodium urate activate the Nod-like receptor protein 3 (NLRP3) inflammasome, resulting in kidney damage. The present study investigated whether the NLRP3 inflammasome is associated with the progression of hyperuricaemia and gouty nephropathy. Adult male patients were recruited at the Affiliated Baoan Hospital of Shenzhen and divided into three groups of 15 patients each: The control group, the hyperuricaemia group and the gouty nephropathy group. General characteristics and organ function indicators were also measured for each patient. NLRP3, apoptosis-associated speck like protein (ASC) and caspase-1 mRNA and protein expressions in peripheral blood mononuclear cells were detected. The expression of certain downstream inflammatory factors, including interleukin (IL)-1β and IL-18 were also assessed in plasma. The results demonstrated that the concentration of uric acid and creatinine were increased in the hyperuricaemia and gouty nephropathy groups compared with the control group. NLRP3, ASC and caspase-1 mRNA and protein expression, and IL-1β and IL-18 expression were increased in the hyperuricaemia and gouty nephropathy groups compared with the control group. In addition, ASC and caspase-1 mRNA and protein expression, and IL-1β expression were higher in the gouty nephropathy group compared with the hyperuricaemia group. In conclusion, the present results supported the hypothesis that the NLRP3 inflammasome signalling pathway is associated with gouty nephropathy leading to initiation of the inflammatory response and causing renal damage.

背景与目标： ：尿酸单钠的结晶沉积物会激活Nod样受体蛋白3（NLRP3）炎性小体，导致肾脏损害。本研究调查了NLRP3炎性体是否与高尿酸血症和痛风性肾病的进展有关。深圳市宝安附属医院招募成年男性患者，分为三组，每组15例：对照组，高尿酸血症组和痛风性肾病组。还测量了每位患者的一般特征和器官功能指标。检测外周血单个核细胞中的NLRP3，凋亡相关斑点样蛋白（ASC）和caspase-1 mRNA和蛋白表达。血浆中还评估了某些下游炎症因子的表达，包括白介素（IL）-1β和IL-18。结果表明，与对照组相比，高尿酸​​血症和痛风性肾病组的尿酸和肌酐浓度升高。与对照组相比，高尿酸​​血症和痛风性肾病组的NLRP3，ASC和caspase-1 mRNA和蛋白表达以及IL-1β和IL-18表达升高。此外，与高尿酸血症组相比，痛风性肾病组的ASC和caspase-1 mRNA和蛋白表达以及IL-1β表达更高。总之，本研究结果支持以下假设：NLRP3炎性体信号通路与痛风性肾病有关，从而导致炎症反应的开始并引起肾脏损害。

BACKGROUND & AIMS: :Fc receptor-like (FCRL) 4 is an immunoregulatory receptor expressed on a subpopulation of human memory B cells of mucosa-associated lymphoid tissue. Fc receptor function of FCRL4 was demonstrated by binding of IgA to FCRL4 following heat aggregation of the Ig. In this study, we demonstrate that FCRL4 recognizes J chain-linked systemic IgA in the absence of heat aggregation. We further demonstrate that mucosal secretory IgA is not recognized by FCRL4 and that systemic IgA binding can be competitively inhibited by recombinant secretory component protein. Finally, we provide evidence that primary FCRL4-bearing human memory B cells are constitutively bound to IgA. Our study provides a mechanism for the negative regulatory activity of FCRL4 on AgR-mediated B cell activation.

背景与目标： ：Fc受体样（FCRL）4是一种在与黏膜相关的淋巴组织的人类记忆B细胞亚群上表达的免疫调节受体。在Ig热聚集后，IgA与FCRL4的结合证明了FCRL4的Fc受体功能。在这项研究中，我们证明了FCRL4在不存在热聚集的情况下识别J链连接的全身IgA。我们进一步证明，粘膜分泌型IgA不被FCRL4识别，全身性IgA结合可被重组分泌成分蛋白竞争性抑制。最后，我们提供的证据表明，携带原代FCRL4的人类记忆B细胞与IgA组成性结合。我们的研究为FCRL4对AgR介导的B细胞活化的负调控活性提供了一种机制。

BACKGROUND & AIMS: :Suppression of rheumatoid factor (RF) production in rheumatoid arthritis (RA) has been variably attributed to the use of remittive agents per se or to clinical improvement associated with their use. There have been conflicting reports with regard to the influence of methotrexate (MTX) on serum RF levels in RA. We determined IgM-RF and IgA-RF levels in paired serum samples (obtained at study entry and completion) from RA patients enrolled in multicenter trials with the Cooperative Systematic Studies of Rheumatic Diseases program. After exclusion of the 14 IgM-RF-negative sera, there were samples from 30 MTX-treated patients and 52 placebo-treated patients. Changes in IgM-RF and IgA-RF levels were weakly associated with each other. Significant decreases in IgM-RF levels were observed in the MTX-treated patients, but not in the placebo group. These changes were most significant in the MTX-treated patients who improved clinically. There were significant decreases in IgA-RF levels at study completion among MTX-treated patients who had improved clinically and those who had not improved clinically, but not in the placebo group. The contributions of clinical improvement and MTX treatment to changes in serum IgM-RF and IgA-RF levels were examined using a logistic regression model. Changes in IgM-RF were strongly related to MTX treatment and, to a lesser extent, to clinical improvement; changes in IgA-RF were related only to MTX treatment. These results indicate that MTX treatment per se decreases both IgM-RF and IgA-RF levels, whereas clinical improvement correlates with decreased IgM-RF levels only.(ABSTRACT TRUNCATED AT 250 WORDS)

背景与目标： ：在类风湿关节炎（RA）中抑制类风湿因子（RF）的产生已被归因于使用释放剂本身或与使用它们相关的临床改善。关于甲氨蝶呤（MTX）对RA血清RF水平的影响，有相互矛盾的报道。我们通过风湿性疾病合作系统研究计划参加了多中心试验的RA患者的配对血清样本（在研究进入和完成时获得）中确定了IgM-RF和IgA-RF的水平。排除14种IgM-RF阴性血清后，有30名接受MTX治疗的患者和52名接受安慰剂治疗的患者的样本。 IgM-RF和IgA-RF水平的变化之间存在弱关联。在接受MTX治疗的患者中观察到IgM-RF水平显着降低，但在安慰剂组中未观察到。这些变化在经MTX治疗且临床上有所改善的患者中最为显着。在研究完成时，在临床上有所改善和在临床上没有改善的患者中，但在安慰剂组中，在研究结束时，IgA-RF水平显着降低。使用逻辑回归模型检查了临床改善和MTX治疗对血清IgM-RF和IgA-RF水平变化的贡献。 IgM-RF的变化与MTX治疗密切相关，在较小程度上与临床改善密切相关。 IgA-RF的变化仅与MTX治疗有关。这些结果表明，MTX治疗本身会降低IgM-RF和IgA-RF水平，而临床改善仅与IgM-RF水平降低相关（摘要截断为250个字）

BACKGROUND & AIMS: :The aim of the present study was to investigate the involvement of B cell‑activating factor (BAFF) in the pathogenesis of IgA nephropathy by activating the tumor necrosis factor receptor‑associated factor 6 (TRAF6)/NF‑κB signaling pathway in glomerular mesangial cells. For the clinical analysis, blood, urine and kidney tissue samples were collected from 58 patients diagnosed with primary IgA nephropathy by renal biopsy. For the in vitro study, glomerular mesangial cells were divided into five groups: Control (con)‑short hairpin RNA (shRNA) (control group); con‑shRNA + BAFF (20 ng/ml); con‑shRNA + BAFF + BAFF‑RFc chimera protein (500 µg/ml); TRAF6‑shRNA; and TRAF6‑shRNA + BAFF (20 ng/ml). For the in vivo experiments, 60 Sprague‑Dawley rats were randomly divided into four groups: Con‑small interfering RNA (siRNA) (control group); con‑siRNA + IgA (IgA nephropathy group), BAFF‑RFc chimera protein (2 µg/ml) + IgA, and TRAF6‑siRNA (0.2 µM) + IgA. Reverse transcription‑quantitative PCR was performed to evaluate the mRNA expression levels of TRAF6, connective tissue growth factor (CTGF), fibronectin (FN) and NF‑κBP65. Western blot analysis was used to detect the protein expression levels of TRAF6, FN, CTGF and phosphorylated‑NF‑κBP65 in glomerular mesangial cells and kidney tissues. The results revealed that plasma BAFF levels were positively correlated with the severity of pathological damage in patients with IgA nephropathy. In vitro, BAFF induced the mRNA and protein expression of TRAF6, CTGF, FN and NF‑κBP65 in glomerular mesangial cells. After the BAFF‑RFc chimera protein was added to inhibit the binding of BAFF and BAFF‑receptor (‑R), this effect was reduced. In vivo, inhibition of the effects of BAFF via injection with the BAFF‑R Fc chimera protein reduced kidney damage in rats suffering from IgA nephropathy. The effect on the expression of signaling pathway‑associated proteins was also alleviated. In conclusion, BAFF enhanced the expression of fibroblast factors in the kidneys by activating the TRAF6/NF‑κB signaling pathway.

背景与目标： ：本研究的目的是通过激活肾小球系膜中的肿瘤坏死因子受体相关因子6（TRAF6）/NF-κB信号通路，研究B细胞激活因子（BAFF）在IgA肾病发病机制中的参与细胞。为了进行临床分析，收集了58例经肾活检诊断为原发性IgA肾病的患者的血液，尿液和肾脏组织样本。对于体外研究，将肾小球系膜细胞分为五组：对照组（con）-短发夹RNA（shRNA）（对照组）；肾小球系膜细胞（shRNA）。 con‑shRNA BAFF（20 ng / ml）； con‑shRNA BAFF BAFF‑RFc嵌合蛋白（500 µg / ml）； TRAF6-shRNA；和TRAF6‑shRNA BAFF（20 ng / ml）。对于体内实验，将60只Sprague-Dawley大鼠随机分为四组：超小型干扰RNA（siRNA）（对照组）； con‑siRNA IgA（IgA肾病组），BAFF‑RFc嵌合蛋白（2 µg / ml）IgA和TRAF6‑siRNA（0.2 µM）IgA。进行逆转录定量PCR评估TRAF6，结缔组织生长因子（CTGF），纤连蛋白（FN）和NF-κBP65的mRNA表达水平。 Western blot分析用于检测肾小球系膜细胞和肾组织中TRAF6，FN，CTGF和磷酸化的NF-κBP65的蛋白表达水平。结果显示，血浆BAFF水平与IgA肾病患者的病理损害严重程度呈正相关。在体外，BAFF诱导肾小球系膜细胞中TRAF6，CTGF，FN和NF-κBP65的mRNA和蛋白表达。加入BAFF‑RFc嵌合蛋白以抑制BAFF和BAFF受体（‑R）结合后，这种作用减弱了。在体内，通过注射BAFF‑R Fc嵌合蛋白抑制BAFF的作用可减少IgA肾病大鼠的肾脏损害。也减轻了对信号通路相关蛋白表达的影响。总之，BAFF通过激活TRAF6 / NF‑κB信号通路增强了肾脏中成纤维细胞因子的表达。

BACKGROUND & AIMS: AIMS/HYPOTHESIS:Diabetic nephropathy, characterised by persistent proteinuria, hypertension and progressive kidney failure, affects a subset of susceptible individuals with diabetes. It is also a leading cause of end-stage renal disease (ESRD). Non-synonymous (ns) single nucleotide polymorphisms (SNPs) have been reported to contribute to genetic susceptibility in both monogenic disorders and common complex diseases. The objective of this study was to investigate whether nsSNPs are involved in susceptibility to diabetic nephropathy using a case-control design. METHODS:White type 1 diabetic patients with (cases) and without (controls) nephropathy from eight centres in the UK and Ireland were genotyped for a selected subset of nsSNPs using Illumina's GoldenGate BeadArray assay. A chi (2) test for trend, stratified by centre, was used to assess differences in genotype distribution between cases and controls. Genomic control was used to adjust for possible inflation of test statistics, and the False Discovery Rate method was used to account for multiple testing. RESULTS:We assessed 1,111 nsSNPs for association with diabetic nephropathy in 1,711 individuals with type 1 diabetes (894 cases, 817 controls). A number of SNPs demonstrated a significant difference in genotype distribution between groups before but not after correction for multiple testing. Furthermore, neither subgroup analysis (diabetic nephropathy with ESRD or diabetic nephropathy without ESRD) nor stratification by duration of diabetes revealed any significant differences between groups. CONCLUSIONS/INTERPRETATION:The nsSNPs investigated in this study do not appear to contribute significantly to the development of diabetic nephropathy in patients with type 1 diabetes.

背景与目标： 目的/假设：糖尿病性肾病的特征是持续性蛋白尿，高血压和进行性肾衰竭，影响了一部分易感糖尿病患者。它也是终末期肾病（ESRD）的主要原因。据报道，非同义（ns）单核苷酸多态性（SNP）有助于单基因疾病和常见复杂疾病的遗传易感性。这项研究的目的是调查病例对照设计是否nsSNPs参与糖尿病肾病的易感性。
方法：使用Illumina的GoldenGate BeadArray测定法，对来自英国和爱尔兰八个中心的患有（病例）和没有（对照）肾病的白人1型糖尿病患者进行基因分型，以筛选出选定的nsSNP子集。按中心分层的卡氏（2）趋势检验用于评估病例与对照之间基因型分布的差异。使用基因组控制来调整测试统计数据的可能膨胀，使用错误发现率方法解释多种测试。
结果：我们评估了1,111 nsSNP与1711例1型糖尿病患者（894例，817例对照）的糖尿病肾病相关性。许多SNPs在校正多个测试之前但没有校正后，各组之间的基因型分布存在显着差异。此外，亚组分析（伴有ESRD的糖尿病性肾病或未伴有ESRD的糖尿病性肾病）和糖尿病持续时间的分层均未显示各组之间的任何显着差异。
结论/解释：本研究中研究的nsSNPs似乎对1型糖尿病患者的糖尿病性肾病的发生没有显着贡献。

BACKGROUND & AIMS: :The incidence of diabetes mellitus (DM) has increased alarmingly over the last decades. Despite taking measures aimed at controlling hyperglycaemia and blood pressure, the rate of end-stage renal disease (ESRD) is continually growing. Upon increased amounts of advanced glycation end products (AGEs) and their correspondent receptors (RAGEs), AGE-RAGE axis is over-activated in DM, being the first step in the initiation and propagation of inflammatory cascades. Meanwhile, HMGB1, released from damaged cells in the diabetic kidneys, is the most notable ligand for the highly expressed toll-like receptors (TLRs) and RAGEs. TLRs play an indispensable role in the pathogenesis of diabetic nephropathy. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are hypoglycaemic agents acting on the renal proximal tubules to prevent glucose reabsorption and therefore increase urinary glucose excretion. Besides improving glycaemic control, these hypoglycaemic agents possess direct renoprotective properties. Here, therefore, we review the most recent findings regarding interrelationship between SGLT2 inhibitors and HMGB1-TLR4 axis.

背景与目标： 在过去的几十年中，糖尿病（DM）的发病率惊人地增加了。尽管采取了旨在控制高血糖和血压的措施，但终末期肾病（ESRD）的发病率仍在不断增长。随着高级糖基化终产物（AGEs）及其对应受体（RAGEs）数量的增加，在DM中AGE-RAGE轴被过度激活，这是引发和传播炎症级联反应的第一步。同时，从糖尿病肾脏受损细胞释放的HMGB1是高表达的Toll样受体（TLR）和RAGE的最显着配体。 TLR在糖尿病性肾病的发病机理中起着不可或缺的作用。葡萄糖钠共转运蛋白2（SGLT-2）抑制剂是降血糖药，作用在肾近端小管上，以防止葡萄糖重吸收并因此增加尿中葡萄糖的排泄。这些降血糖剂除了改善血糖控制外，还具有直接的肾脏保护特性。因此，在这里，我们回顾了有关SGLT2抑制剂和HMGB1-TLR4轴之间相互关系的最新发现。