HO-1 在肝肾疾病中的作用研究进展

血红素氧合酶是血红素降解的限速酶,与酶解产物胆红素、CO-道,共同发挥着抗氧化、抗炎、抑制细胞凋亡、改善组织微循环等作用。血红素氧合酶1是血红素氧合酶的诱导型在脓毒血症、高血压、急性肺损伤等多种疾病中均呈现适应性诱导表达并产生相应的细胞保护作用在肝脏缺血再灌注损伤、肝硬化、肝衰竭、肝移植、急性肾损伤、移植肾损伤等疾病中也发挥着细胞保护作用。本文综述了近年来血红素氧合酶1在肝肾疾病中作用的研究进展,以期为未来治疗方法带来新突破。     

骨髓间充质干细胞移植与肾脏病

骨髓间充质干细胞是目前广受关注的一群成体干细胞,具有取材容易,增殖能力强,生物学特性稳定,可以跨胚层分化,低免疫源性,参与受损组织修复等优点,随着组织工程的兴起和发展以及其自身所特有的生物学特性,人们逐渐认识到将骨髓间充质干细胞作为肾脏病移植治疗的种子细胞具有良好的应用前景。本文就骨髓间充质干细胞的生物学特性及其在肾脏病移植治疗中的进展做一综述。     

骨髓间充质干细胞移植与肾脏病

骨髓间充质干细胞是目前广受关注的一群成体干细胞,具有取材容易,增殖能力强,生物学特性稳定,可以跨胚层分化,低免疫源性,参与受损组织修复等优点,随着组织工程的兴起和发展以及其自身所特有的生物学特性,人们逐渐认识到将骨髓间充质干细胞作为肾脏病移植治疗的种子细胞具有良好的应用前景。本文就骨髓间充质干细胞的生物学特性及其在肾脏病移植治疗中的进展做一综述。     

Early Stage Chronic Kidney Disease Diagnosis by Applying Data Mining Methods to Urinalysis,Blood Analysis and Disease History

Background

Chronic kidney disease (CKD) is a disorder associated with breakdown of kidney structure and function. CKD can be diagnosed in its early stage only by experienced nephrologists and urologists (medical experts) using the disease history, symptoms and laboratory tests. There are few studies related to the automatic diagnosis of CKD in the literature. However, these methods are not adequate to help the medical experts.

MYH9 基因多态性与肾脏疾病关系研究进展

非肌性肌球蛋白重链9基因,编码非肌性肌球蛋白重链ⅡA,既往研究其与May-Hegglin异常(May-Hegglin anomaly,MHA)、Fechtner综合征(Fechtner syndrome,FTNS)、Sebastian综合征(Sebastian syndrome,SBS)、Epstein综合征(Epstein syndrome,EPS)和Alport样综合征相关。2008年首次用混合连锁不平衡绘图(MALD)方法证实其与非糖尿病终末期肾病及局灶节段性肾小球硬化症相关,后陆续有该基因与高血压肾病、C1q肾病等的相关报道。本文综合国外该基因与肾脏病的相关研究,对其与肾脏病的关系研究进展做一概括,对今后的研究起一定的帮助作用。     

Mitochondrial Protein UCP1 Inhibits the Malignant Behaviors of Triple-negative Breast Cancer through Activation of Mitophagy and Pyroptosis

Triple-negative breast cancer (TNBC) is a massive threat to women''s health due to its high morbidity, malignancy, and the refractory, effective therapeutic option of TNBC is still deficient. The mitochondrial protein showed therapeutic potential on breast cancer, whereas the mechanism and downstream pathway of mitochondrial uncoupling protein 1 (UCP1) was not fully elucidated. We found that UCP1 was negatively regulated to the process of TNBC. Overexpressing UCP1 could inhibit the proliferation and metastasis of TNBC, meanwhile inducing the mitochondrial swelling and activation of mitophagy in vitro. Mitophagy activation was then assessed to elucidate whether it was downstream of UCP1 in TNBC metastasis. GSDME is the core of pyroptosis. We found that GSDME was activated in the TNBC cells when UCP1 levels were high. It regulates TNBC cell proliferation potential instead of the apoptosis process in vitro and in vivo. Our results suggested that UCP1 could inhibit the process of TNBC by activating mitophagy and pyroptosis. Impaired activation of mitophagy weakens the regulation effect of UCP1 on metastasis of TNBC, similar to the impairment of GSDME activation on the proliferation regulation of UCP1 on TNBC. UCP1 might be a novel therapeutic target of TNBC.     

尿铜蓝蛋白、肾损伤因子1与糖尿病肾病患者肾功能的关系及对预后不良的预测价值研究

摘要 目的：探讨尿铜蓝蛋白（CP）、肾损伤因子1（KIM-1）与糖尿病肾病（DKD）患者肾功能的关系及对预后不良的预测价值。方法：回顾性分析2017年1月～2019年1月陆军第八十二集团军医院肾内科收治的160例DKD患者（DKD组）的临床资料,随访3年,根据是否发展为终末期肾脏疾病（ESRD）分为预后不良组42例和预后良好组118例,另选取同期56例单纯2型糖尿病（T2DM）患者作为T2DM组和47例体检健康者作为对照组。采用微量法和酶联免疫吸附试验法检测尿CP、KIM-1水平,并计算尿白蛋白/肌酐比值（UACR）和估算肾小球滤过率（eGFR）。通过Spearman相关性分析DKD患者尿CP、KIM-1与UACR、eGFR的相关性,单因素和多因素Logistic回归分析DKD患者预后不良的影响因素,受试者工作特征（ROC）曲线分析尿CP、KIM-1对DKD患者预后不良的预测价值。结果：随访3年,160例DKD患者有42例发展为ESRD,预后不良发生率为26.25％（42/160）。DKD组尿CP、KIM-1、UACR高于T2DM组、对照组,eGFR低于T2DM组、对照组（P＜0.05）;T2DM组尿CP、KIM-1、UACR高于对照组,eGFR低于对照组（P＜0.05）。Spearman相关性分析显示,DKD患者尿CP、KIM-1与UACR呈正相关（P均＜0.001）,与eGFR呈负相关（P均＜0.001）。多因素Logistic回归分析显示,高血压、DKD分期4期和糖化血红蛋白（HbA1c）（较高）、低密度脂蛋白胆固醇（LDL-C）（较高）、UACR（较高）、尿CP（较高）、尿KIM-1（较高）为DKD患者预后不良的独立危险因素（P＜0.05）,eGFR（较高）为独立保护因素（P＜0.05）。ROC曲线分析显示,尿CP、KIM-1联合预测DKD患者预后不良的曲线下面积大于各指标单独预测。结论：DKD患者尿CP、KIM-1升高与肾功能降低和预后不良密切相关,尿CP、KIM-1联合预测DKD患者预后不良的价值较高。     

Applications of Metabolomics for Kidney Disease Research

Metabolomics is one of the relative newcomers of the omics techniques and is likely the one most closely related to actual real-time disease pathophysiology. Hence, it has the power to yield not only specific biomarkers but also insight into the pathophysiology of disease. Despite this power, metabolomics as applied to kidney disease is still in its early adolescence and has not yet reached the mature stage of clinical application, i.e., specific biomarker and therapeutic target discovery. On the other hand, the insight gained from hints into what makes these diseases tick, as is evident from the metabolomics pathways which have been found to be altered in kidney cancer, are now beginning to bear fruit in leading to potential therapeutic targets. It is quite likely that, with greater numbers of clinical materials and with more investigators jumping into the field, metabolomics may well change the course of kidney disease research.     

左卡尼汀与肾脏疾病的关系

左卡尼汀是人体脂类代谢的重要介质,它主要在肾脏代谢,因此肾脏功能与体内左卡尼汀水平直接相关。慢性肾病、终末期肾病及其临床上所采用的血液透析、腹膜透析和肾脏移植等治疗方法对人体内左卡尼汀水平均有影响;人体内左卡尼汀缺乏,易导致在透析过程中出现低血压、贫血、肌无力和疲劳等临床症状,补充左卡尼汀能有效改善这些症状,并能有效减少EPO用量和降低群体反应性抗体水平,减轻环孢素A的肾毒性。因此,本文就肾脏疾病与左卡尼汀的关系和左卡尼汀在肾脏疾病治疗中的应用做一综述。     

Pyroptosis,and its Role in Central Nervous System Disease

Pyroptosis is an inflammatory form of cell death executed by transmembrane pore-forming proteins known as gasdermins and can be activated in an inflammasome-dependent or -independent manner. Inflammasome-dependent pyroptosis is triggered in response to pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) and has emerged as an important player in the pathogenesis of multiple inflammatory diseases, mainly by releasing inflammatory contents. More recently, numerous studies have revealed the intricate mechanisms of pyroptosis and its role in the development of neuroinflammation in central nervous system (CNS) diseases. In this review, we summarize current understandings of the molecular and regulatory mechanisms of pyroptosis. In addition, we discuss how pyroptosis can drive different forms of neurological diseases and new promising therapeutic strategies targeting pyroptosis that can be leveraged to treat neuroinflammation.     

Relationship Between Hyperuricemia and Chronic Kidney Disease

Because approximately 70% of uric acid is excreted from the kidney, hyperuricemia occurs when renal function deteriorates. Until now, it has not been clear if the hyperuricemia seen in such renal diseases plays a role in the progression of renal disease. However, recent clinical studies show that the serum uric acid value is closely associated with hypertension in hyperuricemic patients (cross-sectional study), and also with the onset of hypertension (longitudinal study). Furthermore, one interesting report shows that treatment of hyperuricemia with allopurinol lowers blood pressure in juvenile essential hypertension patients with hyperuricemia. In addition, it is well known that hyperuricemia is closely associated with chronic kidney disease (CKD), is a risk factor for renal insufficiency in general populations, and is a poor prognostic factor of renal function in patients who also have IgA nephropathy. On the other hand, in intervention studies on hyperuricemia, the treatment of hyperuricemia with allopurinol in CKD has resulted in a fall in blood pressure and inhibition of the progression of renal damage. Conversely, the cessation of allopurinol treatment in CKD was followed by a rise in blood pressure and the development of renal damage. Furthermore, the rise of blood pressure and development of renal damage following cessation of allopurinol treatment are only seen in patients not receiving angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB). This suggests that the renin angiotensin (RA) system plays an important role in the development of hypertension and renal damage from hyperuricemia.     

Pyroptosis in Steatohepatitis and Liver Diseases

Pyroptosis is an inflammatory form of regulated cell death, which functions in the clearance of intracellularly replicating pathogens by cell lysis in order to induce further immune response. Since the discovery of the gasdermin (GSDM) family, pyroptosis has attracted attention in a wide range of inflammatory diseases such as nonalcoholic steatohepatitis and other liver diseases. Due to the cleavage of GSDMs by different caspases, the amino-terminal GSDM fragments form membrane pores essential for pyroptosis that facilitate the release of inflammatory cytokines by loss of ionic gradient and membrane rupture. In this review, we address the key molecular and cellular processes that induce pyroptosis in the liver and its significance in the pathogenesis of common liver diseases in different human and experimental mice studies.     

Efficacy of Benzbromarone in Hyperuricemic Patients Associated with Chronic Kidney Disease

We have retrospectively evaluated the uric acid control status and renal function changes over a period of up to 7 years in 35 patients with renal impairment who had stage 3 or higher chronic kidney disease (CKD; stage 3 in 32 patients, stage 4 in 2 patients, and stage 5 in 1 patient) associated with hyperuricemia and were receiving monotherapy with benzbromarone as an antihyperuricemic drug. Serum uric acid levels significantly decreased from 8.5 ± 0.9 to 6.1 ± 0.8 mg/dL at 6 months and were subsequently controlled at less than 7.0 mg/dL in most patients. Most patients received benzbromarone at a dose of 25–50 mg/day, whereas 150–200 mg/day was used in some patients with stage 4 or 5 CKD. No significant changes in estimated glomerular filtration rate (eGFR) from the baseline value of 46.2 ± 11.5 mL/minute/1.73 m² were found after benzbromarone therapy. Although the renal function impairment did not improve by reducing the serum uric acid levels with benzbromarone, the renal function did not deteriorate further on the therapy. These results suggest that benzbromarone is applicable to the management of hyperuricemia associated with renal impairment.     

成人型多囊肾病的遗传研究

３＇ＨＶＲ是成人型多囊肾病基因诊断中最常用的探针。我们分析了５１个无亲缘关系健康学生和３个成人多囊肾病家系的３＇ＨＶＲ－ＰｖｕＩＩ ＲＦＬＰ,所得多态信息用计算机软件ＬＩＮＫ－ＡＧＥ和ＨＯＭＯＧ进行连锁分析和同质性检验,其中１个家系致病基因位点与３＇ＨＶＲ不连锁,因而判定为ｎｏｎ ＰＫＤ１。剩下的两个家系中１个有明显的重组,但还不能判定为ｎｏｎ ＰＫＤ１,另１个与３＇ＨＶＲ连锁,属于ＰＫＤ１。成人     

视黄醇结合蛋白4对肾脏疾病早期诊断的评估

视黄醇结合蛋白4(RBP4)是一类合成于肝脏且广泛分布于人体血液、尿液等其它体液中的维生素A运载蛋白,它在协助维生素A发挥生理功能中起着决定性的作用。近年来的研究表明:当近端肾小管受损时,人体血液或尿液中视黄醇结合蛋白4的含量会出现不同程度的升高。同时它与糖尿病肾病、营养性疾病的发展等其它疾病都在临床上存在着一定的相关性。临床上已将RBP4的含量测定作为判定肾功能有效且成熟的指标之一。目前临床上对视黄醇结合蛋白4的检测主要是传统的酶联免疫法、免疫比浊法等,近年来随着研究水平的不断提高,对RBP4的检测方法已有逐渐转向新型的快速检测方法的趋势。本文在对视黄醇结合蛋白4的理化性质、在肾脏等各类疾病方面的应用以及新型临床检测方法等方面作一综述,随着研究的不断完善,视黄醇结合蛋白4的更多临床意义将逐渐显现。     

Spectral Karyotyping to Study Chromosome Abnormalities in Humans and Mice with Polycystic Kidney Disease

Conventional method to identify and classify individual chromosomes depends on the unique banding pattern of each chromosome in a specific species being analyzed ^{1, 2}. This classical banding technique, however, is not reliable in identifying complex chromosomal aberrations such as those associated with cancer. To overcome the limitations of the banding technique, Spectral Karyotyping (SKY) is introduced to provide much reliable information on chromosome abnormalities.SKY is a multicolor fluorescence in-situ hybridization (FISH) technique to detect metaphase chromosomes with spectral microscope ^{3, 4}. SKY has been proven to be a valuable tool for the cytogenetic analysis of a broad range of chromosome abnormalities associated with a large number of genetic diseases and malignancies ^{5, 6}. SKY involves the use of multicolor fluorescently-labelled DNA probes prepared from the degenerate oligonucleotide primers by PCR. Thus, every chromosome has a unique spectral color after in-situ hybridization with probes, which are differentially labelled with a mixture of fluorescent dyes (Rhodamine, Texas Red, Cy5, FITC and Cy5.5). The probes used for SKY consist of up to 55 chromosome specific probes ^7-10.The procedure for SKY involves several steps (Figure 1). SKY requires the availability of cells with high mitotic index from normal or diseased tissue or blood. The chromosomes of a single cell from either a freshly isolated primary cell or a cell line are spread on a glass slide. This chromosome spread is labeled with a different combination of fluorescent dyes specific for each chromosome. For probe detection and image acquisition,the spectral imaging system consists of sagnac interferometer and a CCD camera. This allows measurement of the visible light spectrum emitted from the sample and to acquire a spectral image from individual chromosomes. HiSKY, the software used to analyze the results of the captured images, provides an easy identification of chromosome anomalies. The end result is a metaphase and a karyotype classification image, in which each pair of chromosomes has a distinct color (Figure 2). This allows easy identification of chromosome identities and translocations. For more details, please visit Applied Spectral Imaging website (http://www.spectral-imaging.com/).SKY was recently used for an identification of chromosome segregation defects and chromosome abnormalities in humans and mice with Autosomal Dominant Polycystic Kidney Disease (ADPKD), a genetic disease characterized by dysfunction in primary cilia ^11-13. Using this technique, we demonstrated the presence of abnormal chromosome segregation and chromosomal defects in ADPKD patients and mouse models ¹⁴. Further analyses using SKY not only allowed us to identify chromosomal number and identity, but also to accurately detect very complex chromosomal aberrations such as chromosome deletions and translocations (Figure 2).     

铁死亡与肾脏疾病相关性的研究进展

铁死亡(ferroptosis)是2012年新发现的一种非凋亡的细胞死亡形式,其实质是依赖铁离子的活性氧(reactive oxygen species,ROS)和脂质氢过氧化物蓄积导致的线粒体形态改变和细胞膜磷脂过氧化损伤。铁死亡与许多肾脏疾病的病理生理进程密切相关。然而铁死亡参与肾脏疾病损伤的分子生物学机制尚缺乏系统和深入的认识。针对铁死亡的调控机制、研究进展及其在肾脏相关疾病中的作用作一综述,以期为肾脏疾病的治疗提供新思路、新靶点。     

老龄活体供肾研究新进展

本文主要从老龄供肾优缺点分析,老龄供肾特征性改变情况分析,老龄供肾移植后功能变化分析,老龄供肾必须遵循的法律与伦理标准,取肾原则及疗效评估等多层次阐述了国内外老龄供肾在肾移植手术中的新进展,同时对其发展瓶颈与前景进行了剖析。