芪地固肾方治疗特发性膜性肾病的临床分析

目的:回顾性分析芪地固肾方治疗特发性膜性肾病(IMN)的临床疗效与安全性。方法:选取2014年1月至2017年6月陕西中医药大学附属医院肾病科门诊及住院IMN患者141例,根据用药方案分为西药组(西药标准疗法)、中西药结合组(芪地固肾方+西药标准疗法)和中药组(芪地固肾方)3组各47例,观察3组患者治疗后临床疗效、复发率及不良反应等。结果:治疗6个月后,中西药结合组和西药组总有效率72.34%、68.09%高于中药组,治疗12个月时3组有效率比较差异无统计学意义,治疗18个月后中药组和中西药结合组总有效率75.76%、78.72%高于西药组。中药组和中西药结合组在治疗12个月和18个月后较西药组在提高中医证候疗效、减少中医证候积分上更具优势。中药组和中西药结合组复发率更低,3组均未出现严重不良反应。结论:芪地固肾方能提高IMN缓解率,在提高中医证候疗效、降低复发率上更具优势,远期疗效可观,值得进一步推广应用。     

Efficacy of cyclosporin in difficult-to-treat idiopathic membranous nephropathy

SUMMARY: Poor tolerance and the potential long-term toxicity have limited the widespread use of corticosteroids and cytotoxic drugs in the treatment of idiopathic membranous nephropathy (IMN). Cyclosporin A (CyA) has been proven to be a less toxic alternative, but its efficacy needs further confirmation. Cyclosporin A (2–3mg/kg per day) in combination with low-dose methylprednisolone (4mg/day) was given to 28 nephrotic patients with IMN who had failed to respond, or tolerate, or to complete treatments with steroids and/or cytotoxic drugs. the mean duration of treatment was 11 ± 7 months. Seven patients (25%) showed a complete remission of proteinuria, 17 (60%) a partial one, and four (15%) did not respond at all. the average time to achieve optimal remission was 4.2 ± 1.4 weeks following the initiation of therapy. In those who responded completely or partially, plasma creatinine (Per) did not change significantly from pre CyA levels during follow up (1.0 ± 0.3 vs 1.2 ± 0.3mg/dL, P =NS). the remaining four patients who had renal insufficiency already before CyA (mean Per: 2.1 ± 0.8mg/dL), showed a rapid deterioration of renal function after the initiation of CyA (mean Per: 3.1 ± 1.5 mg/dL, P <0.01), and as a consequence, the drug was discontinued. A mul-tivariate analysis on the clinical and histological features demonstrated that the degree of renal function impairment ( P <0.02), the percentage of obsolete glomeruli ( P <0.01), and the severity of interstitial fibrosis ( P <0.005) independently predicted the response to therapy. Low dose CyA is an effective and safe alternative treatment for patients with IMN and normal renal function. However, the drug should be given with caution to patients with established renal insufficiency.     

激光治疗膜性白内障：术前干涉视力测定的意义

应用激光干涉视力仪检测了23例(23只眼)膜性白内障Nd:YAG激光切开术前及术后的干涉视力,结果显示:术前与术后干涉视力之间的差异无显著性(P>0.05)。术前干涉视力与术后矫正视力呈正相关(P<0.05),提示半透明膜性白内障对激光干涉视力无显著影响.激光干涉视力是反映术后视力康复的可靠方法.但在具体分析时,应注意假阴性和假阳性的可能.65.2%的眼术后矫正视力高于术后干涉视力,反映了高度屈光不正的无晶体眼对激光干涉条纹在视网膜上的形成有一定的影响.     

造血干细胞移植后慢性移植物抗宿主病相关的膜性肾病一例

目的 总结造血干细胞移植后慢性移植物抗宿主病（cGVHD）相关的膜性肾病的诊疗体会。方法 为1例急性淋巴细胞白血病患者施行HLA全相合的无关供者外周血造血干细胞移植，术后应用甲氨喋呤和他克莫司（FK506）预防GVHD。术后第19d发生急性GVHD，经甲泼尼龙治疗逆转。分别于术后182d、235d停用FK506和泼尼松，5d后患者出现cGVHD表现，肝功能异常，并伴肾病综合征的相关表现，病理诊断为膜性肾病Ⅱ期，遂给予FK506和泼尼松治疗，同时辅以利尿、降脂等措施。结果发生膜性肾病时，患者的尿蛋白＋＋＋＋，白细胞75个／μl，上皮细胞359．5个／pl，病理性管型＋，管型计数为167个／μl，24h尿蛋白定量为4．28g；肾组织活检，无肾小球硬化，肾小球体积稍大，部分血管袢受压，开放欠佳，肾小球基底膜轻微增厚，外观呈僵硬感，系膜基质轻、中度增殖；间质区部分肾小管扩张，肿胀、变性，未见明显间质纤维化和炎症细胞浸润；Masson染色可见基底膜上皮侧嗜复红物沉积；免疫荧光检查，IgG＋＋＋，C3＋＋＋，IgA＋＋，沿毛细血管袢呈颗粒状节段性分布，系膜区呈团块状分布；IgM、Clq、CA均阴性。电镜下可见肾小球基底膜上皮下沉积物，并有基膜增厚，毛细血管系膜基质轻度增生。经泼尼松和FK506治疗，2个月后尿蛋白转阴。结论 造血干细胞移植后出现肾病综合征或蛋白尿，应考虑GVHD相关膜性肾病的可能，肾穿刺活检有助于诊断，糖皮质激素和FK506治疗有效。     

Idiopathic membranous glomerulonephritis in Brazil

Summary: A survey of the medical records and renal biopsy reports of 41 patients with a diagnosis of membranous glomerulonephritis seen at the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo was undertaken between 1961 and April 1992. Twenty-three of these patients were found to have idiopathic membranous glomerulonephritis (IMG) and 22 of them were treated with corticosteroids and/or immunosuppressants. Data for these 22 patients showed that the age at clinical presentation was 36.3± 17.5 years, white skin colour predominated (14 patients), and 15 were males; nephrotic syndrome was the clinical presentation in 20 patients and proteinuria was accidentally discovered in two patients. On the first hospital visit 11 patients presented proteinuria of up to 3 g/24 h and 16 presented serum creatinine below 1.5 mg/dL, and 14 developed renal hypertension during follow up. Clinicalmorphological correlation permitted us to conclude (in agreement with the literature) that advanced patient age, intensity of proteinuria, serum creatinine levels above 1.5 mg/dL on the occasion of the first hospital visit, and arterial hypertension are clinical-laboratory factors indicating a poor prognosis for IMG. More advanced staging of glomerular damage, presence of segmental mesangial sclerosis and tubulointerstitial involvement are microscopic factors indicating a poor prognosis for IMG.     

Interferon-gamma (IFN-gamma) and IL-4 expressed during mercury-induced membranous nephropathy are toxic for cultured podocytes.

The subepithelial immune deposits of Dorus Zadel Black (DZB) rats with mercury-induced membranous nephropathy consist of autoantibodies directed to laminin P1 and of complement. The animals develop massive proteinuria within 10-14 days which is associated with obliteration of foot processes of glomerular visceral epithelial cells (GVEC), or podocytes. Previous studies indicate that these autoantibodies are probably not the sole mediator of proteinuria and GVEC damage. In this study we investigated whether circulating or macrophage-derived cytokines can contribute to the GVEC changes as detected in vivo. In vivo at the height of the proteinuria, increased intraglomerular IFN-gamma immunoreactivity was found. In diseased rats a five-fold increase in intraglomerular macrophages was found, but we could not detect intraglomerular IFN-alpha, IFN-beta, IL-1 beta or tumour necrosis factor-alpha (TNF-alpha) by using immunohistology. Subsequently, we exposed cultured GVEC to these cytokines to investigate their cytotoxic effects on several physiological and structural parameters. IFN-gamma and IL-4 were the only cytokines that exerted toxic effects, resulting in a rapidly decreased transepithelial resistance of confluent monolayers, which was closely associated with altered immunoreactivity of the tight junction protein ZO-1. IL-4 also affected vimentin and laminin immunoreactivity. IFN-gamma and IL-4 only interfered with monolayer integrity when added to the basolateral side of the GVEC, indicating specific (receptor-mediated) effects. Only IL-4 decreased the viability of the cells, and treated monolayers demonstrated an increased passage of the 44-kD protein horseradish peroxidase. From our experiments we concluded that IFN-gamma subtly affected monolayer integrity at the level of the tight junctions, and that IL-4 additionally induced cell death. We hypothesize that the toxic effects of the cytokines IFN-gamma and IL-4 as seen with cultured podocytes are necessary together with the autoantibodies, for the ultimate induction of proteinuria in mercury nephropathy in the DZB rat.     

Tacrolimus versus cyclophosphamide for patients with idiopathic membranous nephropathy and treated with steroids: a systematic review and meta-analysis of randomized controlled trials

BackgroundThe therapeutic effects of tacrolimus (TAC) versus cyclophosphamide (CTX) were not fully illustrated for patients with idiopathic membranous nephropathy (IMN).MethodsThe PubMed, EmBase, Cochrane library, and CNKI were systematically searched throughout March 2020 for randomized controlled trials evaluating the therapeutic effects of TAC versus CTX for IMN patients treated with steroids. The pooled relative risks (RRs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated using the random-effects model.ResultsTwelve trials recruited a total of 868 IMN patients were identified and contained in final meta-analysis. Patients in TAC group was associated with an increased incidence of overall remission (12 trials: 868 patients; RR: 1.21; 95% CI: 1.11–1.31; p < 0.001) and complete remission (12 trials: 868 patients; RR: 1.50; 95% CI: 1.25–1.80; p < 0.001). Moreover, we noted TAC therapy significantly reduced urinary protein excretion (9 trials: 567 patients; WMD: −1.06; 95%CI: −1.41 to −0.71; p < 0.001), and increased serum albumin (9 trials: 567 patients; WMD: 5.37; 95%CI: 2.97 to 7.77; p < 0.001) than CTX therapy. Furthermore, no significant difference between TAC and CTX for serum creatinine was detected (6 trials: 378 patients; WMD: 0.15; 95%CI: −3.46 to 3.75; p = 0.936). Finally, the risk of alopecia (p = 0.008), infection (p = 0.045), leukocytosis (p = 0.002), and elevated ALT/AST (p = 0.011) in TAC group was significantly lower than CTX group, whereas TAC was associated with an increased risk of tremor than CTX (p = 0.010).ConclusionsThis study found IMN patients treated with TAC combined with steroids provides a better therapeutic effect and less adverse events than those treated with CTX combined with steroids, with moderate-certainty evidence.     

膜肾1号方对大鼠肾脏病理及PI3K/Akt/mTOR信号通路表达的影响

[目的] 观察膜肾1号方对膜性肾病大鼠肾脏病理的改善作用及其对自噬通路磷脂肌醇3-激酶（PI3K）/蛋白激酶B（AKT）/雷帕霉素靶蛋白（mTOR）相关蛋白表达的影响。[方法] 将大鼠随机分为对照组、模型组、膜肾1号方高剂量组、中剂量组、低剂量组,盐酸贝那普利组。采用大鼠尾静脉注射阳离子化牛血清白蛋白（C-BSA）的方法建立MN大鼠模型,灌胃、取材。苏木精-伊红（HE ）染色法观察大鼠肾脏组织病理改变;免疫球蛋白G（IgG）免疫荧光染色观察大鼠IgG沉积;蛋白免疫印迹法（Western Blot）检测PI3K/Akt/mTOR 信号通路相关蛋白及自噬相关蛋白轻链3（LC3）表达。[结果] 药物干预后,膜肾1号方组大鼠24 h尿蛋白、三酰甘油、总胆固醇、低密度脂蛋白下降且低于模型组,并具有统计学差异（P＜0.05）。光镜下观察,HE染色示正常组肾组织整体结构基本正常,膜性肾病（MN）模型组肾小球毛细血管丛充血,系膜增生,基底膜出现增厚,部分肾小管细胞空泡变、组织内可见炎症细胞浸润,可见嗜复红蛋白及IgG沉积。经膜肾1号方和盐酸贝那普利干预后,大鼠肾脏病理学改变均有所减轻。各组大鼠IgG沉积显示,与对照组比较模型组IgG沉积明显,IgG荧光表达升高,差异具有统计学意义（P＜0.05）,盐酸贝那普利组和膜肾1号方组IgG荧光表达下降且低于模型组,具有统计学差异（P＜0.05）。Western Blot检测显示,药物干预后,盐酸贝那普利组和膜肾1号方组大鼠PI3K-Akt信号通路相关蛋白表达下降,LC3 表达增加,并具有统计学差异（P＜0.05）。[结论] 膜肾1号方可改善大鼠肾脏病理损伤,膜肾1号方干预后PI3K-Akt信号通路相关蛋白磷酸化磷酸肌醇3激酶（p-PI3K）,磷酸化Akt蛋白（p-Akt）,磷酸化雷帕霉素靶蛋白（p-mTOR）表达明显降低,自噬相关蛋白LC3表达升高,其分子机制与自噬信号通路的调控有关。     

复方黄芪袋泡饮改善慢性冠脉供血不足的研究

复方黄芪袋泡饮改善慢性冠脉供血不足的研究刘志泉＊陈跃＊李岩飞＊丁煜＊为寻找一种比传统扩血管药物更为有效的中西药复方制剂以改善冠脉血供，降低心绞痛和心肌梗塞的发生率，我们依据中西药理论，结合现代血液流变学和微循环的科研成果，研制了以黄芪、阿司匹林为主要...     

经皮穿刺封堵室间隔膜部缺损的应用解剖

目的:为经皮穿刺室间隔膜部缺损的封堵术提供应用解剖学基础。方法:解剖测量38例(男25.女13)正常成年人的心标本的室间隔膜部及周围结构。结果:室间隔膜部的形态可分为三角型、圆型和椭圆型;各型的出现率分别为58％(22例)、23.7％(9例)和18.3％(7例)。室间隔膜部在左室面的高度为(8.79±2.27)mm。右室面高度为(6.43±1.43)mm。室间隔膜部的长度为(9.37±2.52)mm。室间隔膜部上、下、前、后方和中点的厚度分别为(0.80±0.19)mm、(0.70±0.16)mm、(0.78±0.28)mm、(0.75±0.1 5)mm和(0.52±0.13)mm。结论:室间隔膜部以三角型为主,多位于室上嵴的后缘,膜部的左室面高于右室而和靠近右室面,建议封堵器的左室面的面积应大于右室面。