The Donor Kidney Biopsy and Its Implications in Predicting Graft Outcomes: A Systematic Review

Despite a growing organ shortage in the United States, many deceased donor kidneys removed for transplantation are discarded. Kidney biopsy findings often play a role in these discards, although it is not clear whether biopsies reliably inform acceptance decisions. Therefore, we carried out a systematic review of the medical literature on the utility of both procurement and implantation biopsies for predicting posttransplant outcomes. Between January 1, 1994 and July 1, 2014, 47 studies were published in the English language literature that examined the association between pretransplant donor biopsy findings from 50 or more donors (with more than half being from deceased donors) and either posttransplant graft failure, delayed graft function, or graft function. In general, study quality was poor. All were retrospective or did not indicate if they were prospective. Results were heterogeneous, with authors as often as not concluding that biopsy results did not predict posttransplant outcomes. The percent glomerular sclerosis was most often examined, and failed to predict graft failure in 7 of 14 studies. Of 15 semiquantitative scoring systems proposed, none consistently predicted posttransplant outcomes across studies. Routine use of biopsies to help determine whether or not to transplant a kidney should be reexamined.     

Nox2 Is a Mediator of Ischemia Reperfusion Injury

Delayed graft function (DGF) results from ischemia‐reperfusion injury (IRI) and the generation of reactive oxygen species. We hypothesized that NADPH oxidase 2 (Nox2) plays an important role in pathways leading to DGF. We tested this hypothesis in vitro, in an animal model of IRI using wild type and Nox2^?/? mice, and in patients with DGF. Under hypoxic conditions, primary tubular epithelial cells from Nox2^?/? mice had reduced expression of MMP2, vimentin, and HSP27. BUN and creatinine levels were significantly increased in both Nox2^?/? and WT mice at 4 weeks and 6 months after IRI, suggesting the development of acute and chronic kidney injury. At 4 weeks, kidney fibrosis (α‐SMA, picrosirius) and oxidative stress (dihydroethidine, HNE) were significantly reduced in Nox2^?/? mice, confirming the oxidative and pro‐fibrotic effects of Nox2. The molecular signature of IRI using genomic analyses demonstrated a significant decline in hypoxia reponse, oxidative stress, fibrosis, and inflammation in Nox2^?/? mice. Immunohistochemical analyses of pre‐implanatation kidney allograft biopsies from patients with subsequent DGF showed significantly greater Nox2 levels and vascular injury compared with patients without DGF. These studies demonstrate that Nox2 is a modulator of IRI and its absence is associated with reduced inflammation, OS, and fibrosis.

     

HLA‐G*01:04∼UTR3 Recipient Correlates With Lower Survival and Higher Frequency of Chronic Rejection After Lung Transplantation

Lung transplantation (LTx) is a valid therapeutic option for selected patients with end‐stage lung disease. Soluble HLA‐G (sHLA‐G) has been associated with increased graft survival and decreased rejection episodes in solid organ transplantation. HLA‐G haplotypes named UTRs, defined by SNPs from both the 5′URR and 3′UTR, have been reported to reliably predict sHLA‐G level. The aim of this retrospective study was to determine the impact of HLA‐G alleles and UTR polymorphism from LTx recipients on anti‐HLA allo‐immunization risk, overall survival and chronic rejection (CLAD). HLA‐G SNPs were genotyped in 124 recipients who underwent LTx from 1996 to 2010 in Marseille, 123 healthy individuals and 26 cystic fibrosis patients not requiring LTx. sHLA‐G levels were measured for 38 LTx patients at D0, M3 and M12 and for 123 healthy donors. HLA‐G*01:06～UTR2 was associated with a worse evolution of cystic fibrosis (p = 0.005) but not of long‐term survival post‐LTx. HLA‐G*01:04～UTR3 haplotype was associated with lower levels of sHLA‐G at D0 and M3 (p = 0.03), impaired long‐term survival (p = 0.001), increased CLAD occurrence (p = 0.03) and the production of de novo donor‐specific antibodies (DSA) at M3 (p = 0.01). This study is the first to show the deleterious association of different HLA‐G alleles and UTRs in LTx.     

高压氧治疗对阿尔茨海默病大鼠海马内神经元凋亡及p38丝裂原蛋白激酶表达的影响

目的 评价高压氧治疗对阿尔茨海默病(alzheimer's disease,AD)大鼠海马内神经元凋亡及p38丝裂原蛋白激酶(p38 mitogenactivated protein kinases,p38MAPK)表达的影响. 方法 18只雄性SD大鼠,体重260 g～290 g,采用随机数字表法分为3组(每组6只):生理盐水组(NS组),海马区注射生理盐水;阿尔茨海默病组(AD组),海马区注射Aβ1-40;高压氧组(HBO组),海马区注射Aβ1-40,并于术后1 d～7d行每天1次的高压氧治疗.应用脑立体定位仪于大鼠海马区注射Aβ1-40制备AD模型.于术前1d和术后1、7、14、21 d行水迷宫行为学测试.于术后21 d水迷宫行为学测试结束后处死大鼠,采用苏木精-伊红染色(hematoxylin-eosin,HE)方法染色海马组织病理结构,TUNEL法标记检测凋亡细胞,免疫印迹法(Western bolt)法测定海马内p38MAPK蛋白磷酸化水平. 结果 术后21 d时,与NS组比较,AD组大鼠上台前路程和逃避潜伏期增加[(379±41)、(1 978±120) cm,(16.0±2.8)、(78.4±10.8)s](P＜0.05);与AD组比较,HBO组大鼠上台前路程和逃避潜伏期减少[(1978±120)、(1 246±96) cm,(78.4±10.8)、(51.7±6.2)s](P＜0.05).与NS组比较,AD组和HBO组大鼠海马组织细胞凋亡率[(6.3±13)％,(45.2±5.1)％]及p38MAPK蛋白磷酸化表达升高(0.16±0.06),(0.54±0.10)(P＜0.05);与AD组比较,HBO组海马组织细胞凋亡率[(45.2±5.1)％,(22.5±3.7)％]及p38 MAPK蛋白磷酸化表达下降[(0.54±0.10),(0.31±0.08)](P＜0.05).结论 高压氧治疗可有效缓解AD大鼠认知功能障碍,且能够抑制海马内神经元凋亡,其机制与降低p38MAPK的磷酸化水平有关.     

腹壁自体筋膜盆底悬吊术治疗盆底器官脱垂40例

目的探讨腹壁自体筋膜盆底悬吊术治疗盆底器官脱垂的临床疗效和应用价值。方法对40例经腹壁自体筋膜盆底悬吊术治疗的盆底器官脱垂患者进行回顾性分析,术后1个月门诊随访,了解术后近期情况,以后每半年随访1次,随访1年。结果40例患者腹壁自体筋膜盆底悬吊术均在全麻下进行,整体手术时间平均为（133.41±56.57）min（含妇科其他操作,如子宫切除术、卵巢囊肿剥除术、阴道后壁修补术等,单独行盆底悬吊术2例）,平均失血量为（109.71±70.71）mL,术后平均住院时间为（8.94±0.71）d,其中2例因腹部切口液化,术后尿管保留时间为（4.26±1.41）d,其中1例术中膀胱损伤,术后保留导尿14 d。随访1年,2例术后阴道后壁膨出。生活质量未受影响。结论腹壁自体筋膜盆底悬吊术是一种治疗子宫阴道脱垂的简单、有效、容易掌握的手术方式,可以进行临床术式的推广。     

逼尿肌相关蛋白在慢性前列腺炎大鼠模型中的表达及意义

目的：采用17β-雌二醇联合去势建立大鼠慢性非细菌性前列腺炎模型,检测膀胱逼尿肌蛋白在慢性前列腺炎大鼠膀胱的表达。方法取2月龄 SD 雄性大鼠60只随机分为6组,每组10只,即：空白对照组、生理盐水组、假手术组、单纯17β-雌二醇组、单纯去势组、17β-雌二醇联合去势组。HE 染色判定大鼠慢性前列腺炎模型建造成功后,采用 SP 免疫组化法、Western blot 检测6组大鼠膀胱组织肌动蛋白(α-actin)、肌球蛋白(MLC 2)及高分子量钙调素结合蛋白(h-cad)表达的差异。结果免疫组化结果显示17β-雌二醇联合去势组中α-actin、MLC 2、h-cad 蛋白表达增多,Western blot 显示α-actin 在各组的表达,与空白对照组相比,生理盐水组、假手术组、单纯17β-雌二醇组、单纯去势组联合去势组差异有统计学意义。 MLC 2、h-cad 在各组的表达与空白对照组相比,生理盐水组、假手术组差异无统计学意义,单纯17β-雌二醇组、单纯去势组、联合去势组差异有统计学意义。结论α-actin、MLC 2、h-cad 表达变化可能参与慢性前列腺炎排尿相关症状的发病。     

Memory Dysfunction in Type 2 Diabetes Mellitus Correlates with Reduced Hippocampal CA1 and Subiculum Volumes

Background:

Little attention has been paid to the role of subcortical deep gray matter (SDGM) structures in type 2 diabetes mellitus (T2DM)-induced cognitive impairment, especially hippocampal subfields. Our aims were to assess the in vivo volumes of SDGM structures and hippocampal subfields using magnetic resonance imaging (MRI) and to test their associations with cognitive performance in T2DM.

Methods:

A total of 80 T2DM patients and 80 neurologically unimpaired healthy controls matched by age, sex and education level was enrolled in this study. We assessed the volumes of the SDGM structures and seven hippocampal subfields on MRI using a novel technique that enabled automated volumetry. We used Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA) scores as measures of cognitive performance. The association of glycosylated hemoglobin (HbA1c) with SDGM structures and neuropsychological tests and correlations between hippocampal subfields and neuropsychological tests were assessed by partial correlation analysis in T2DM.

Results:

Bilaterally, the hippocampal volumes were smaller in T2DM patients, mainly in the CA1 and subiculum subfields. Partial correlation analysis showed that the MoCA scores, particularly those regarding delayed memory, were significantly positively correlated with reduced hippocampal CA1 and subiculum volumes in T2DM patients. Additionally, higher HbA1c levels were significantly associated with poor memory performance and hippocampal atrophy among T2DM patients.

Conclusions:

These data indicate that the hippocampus might be the main affected region among the SDGM structures in T2DM. These structural changes in the hippocampal CA1 and subiculum areas might be at the core of underlying neurobiological mechanisms of hippocampal dysfunction, suggesting that degeneration in these regions could be responsible for memory impairments in T2DM patients.     

定量三维彩色多普勒超声联合血清β-HCG检查对胎盘功能低下的诊断

目的 评估定量三维彩色能量多普勒超声(three-dimensional color power Doppler ultrasound,3D-CPD)联合β-HCG检查对胎盘功能低下的诊断价值.方法 选择2012年5月至2014年3月在昆明医科大学第四附属医院接受产检的产妇368例,利用GE公司E8三维超声系统对胎盘的血管化指数(VI)、血流指数(FI)和血管化-血流指数(VFI)进行测量,同时利用化学发光法测定β-HCG水平.并存产后记录新生儿体长、体重和生命体征综合评分(Apgar评分).结果 产后共有58例新生儿体重＜2 500 g,为观察组,另外3 10例新生儿体重＞2 500 g,为对照组.对照组VI、FI和VFI分别为(12.5±5.6)、(47.2±3.3)和(9.0±2.6),观察组为(10.2±4.8)、(40.6±4.1)和(4.2±1.7),差异具有统计学意义(P＜0.05);观察组β-HCG水平为(29453.0±229.5) mIU/mL,中位数≥2.5 mom,对照组β-HCG水平为(8 442.6±47.2) mIU/mL,中位数＜2.5mom,观察组β-HCG水平明显高于对照组(P＜0.05);新生儿基本情况相比,观察组新生儿体长、体重和Apgar评分明显低于对照组(P＜0.05).结论 3D-CPD联合β-HCG检查对胎盘功能异常具有重要的诊断价值,有利于围产期了解胎盘功能及估计胎儿预后.     

Cardiac sympathetic innervation and blood flow regulation of the diabetic heart

A key problem in ischemia‐induced impairment of the vascular performance of the diabetic heart is the often‐unrecognized cardiac sympathetic dysfunction. Advanced single‐photon emission computed tomography (SPECT) and positron emission tomography (PET) using the radiopharmaceuticals, ¹²³I‐metaiodobenzylguanidine (¹²³I‐MIBG) and ¹¹C‐hydroxyephedrine (¹¹C‐HED), have shown that dysfunction of cardiac sympathetic nerves is present to a large extent in both type 1 and type 2 diabetes. The pattern of sympathetic disturbances is heterogeneous with a predominant effect in the posterior myocardial region. Furthermore, myocardial blood flow assessment with PET has shown that endothelial‐dependent vasodilatation is reduced in proportion to the magnitude of cardiac sympathetic dysfunction. These mechanisms are currently proposed to lead from early changes to advanced impairment of cardiac function in diabetes. Copyright © 2001 John Wiley & Sons, Ltd.