急性冠状动脉综合征与CD40基因多态性的相关性研究

目的CD40-CD40L信号通路在急性冠状动脉综合征（ACS）的发生发展中起着重要作用。笔者研究湖北地区汉族人群CD40-E1SNP（-1C/T）和E4SNP基因多态性与ACS的关系。方法应用聚合酶链反应限制性片段长度多态性（PCR-RFLP）方法,检测160例经冠状动脉造影确诊的ACS患者（其中男性125例,女性35例,平均年龄63.8岁）和92例冠状动脉造影阴性人群（其中男性72例,女性20例,平均年龄58.8岁）CD40-E1SNP（-1C/T）和E4SNP基因型和等位基因频率,结合血脂及炎性标志物水平分析两组人群CD40基因型和等位基因频率差异。结果CD40-1位点C等位基因频率在ACS组与对照组分别为0.606和0.489,T等位基因频率分别为0.394和0.511,两者差异有统计学意义（P〈0.05）;ACS患者CC基因型频率（0.281）明显高于对照组（0.13）,差异有统计学意义（P〈0.01）;而未检测到CD40-E4SNP基因多态性。结论CD40-1C/T基因多态性与ACS有相关性,C等位基因可能是汉族人群ACS的易感基因,而汉族人群可能不存在CD40-E4SNP基因多态性。     

Hcy、MTHFR基因多态性与急性脑梗死的关系

目的：探讨同型半胱氨酸（Homocysteine,Hcy）及亚甲基四氢叶酸还原酶（MTHFR）基因多态性与急性脑梗死的关系。方法：选取98名急性脑梗死患者以及98名健康志愿者进行性别、年龄和体重指数配对,检测并分析比较两组血浆Hcy浓度以及MTHFR677位点基因型。结果：急性脑梗死组和对照组的Hcy浓度分别为（16.83±5.86）μmol/L和（14.20±5.73）μmol/L,经统计学处理,差异具有统计学意义（P〈0.01）。急性脑梗死组的T等位基因频率（58.2%）显著高于对照组（40.8%）（χ2=11.80,P〈0.01）。急性脑梗死组CC、CT和TT基因型相应的Hcy浓度分别为（14.34±5.25）μmol/L、（16.12±5.87）μmol/L和（18.96±5.58）μmol/L,差异具有统计学意义（F=5.36,P〈0.05）,TT型显著高于CC型与CT型（P值分别为0.002;0.031）。结论：MTHFR基因C677T突变可影响Hcy水平,可能是急性脑梗死的重要发病机制之一。     

急性肾损伤相关生物标志物的研究进展

急性肾损伤(acute kidney injury,AKI)既往被称为急性肾衰竭(acute renal failure,ARF),是一种由不同病因所致、具有不同临床表现并以肾小球滤过率迅速下降为主要特点的临床综合征,多见于多器官功能衰竭、败血症等严重疾病,也常见于各类肾脏疾病的不同阶段.     

中国苏州地区汉族人群MCP-1基因多态性与急性胰腺炎相关性研究

目的探讨中国苏州地区汉族人群单核细胞趋化因子蛋白-1(monocyte chemoattractant protein-1,MCP-1)基因-2518A/G多态性与急性胰腺炎的相关性。方法采用聚合酶链反应-限制性片段长度多态性方法检测中国苏州汉族人群急性胰腺炎(acute pancreatitis,AP)患者101例[其中包括轻症急性胰腺炎(mildAP,MAP)78例,重症急性胰腺炎(servere AP,SAP)23例]和120名健康对照的MCP-1基因-2518位点基因型分布及基因频率,并评价基因多态性与AP易感性之间的相关性。结果对照组MCP-1-2518A/G位点的AA基因型频率较SAP组和MAP组高,差异有统计学意义(P<0.01),携AG及GG基因型者患MAP的风险度约是AA基因型的5.896倍(P<0.01,OR=5.896),患SAP的风险度约为7.011倍(P<0.05,OR=7.011)。而在MAP与SAP组间AA基因型频率差异无统计学意义(P=0.997)。对照组G等位基因频率明显低于MAP(P<0.01,OR=0.318)和SAP组(P<0.01,OR=0.309)。但G等位基因频率在MAP与SAP组间基因型分布差异无统计学意义(P=0.623,OR=1.211)。结论中国苏州地区汉族人群MCP-1-2518位点AA基因型可能有助于保护机体避免发生AP,G等位基因频率较高的人可能易患AP。但AA基因型和G等位基因频率不能预测SAP的发生。     

RFC-1基因多态性与急性脑梗塞的相关性研究

目的 对CRF-1基因多态性与急性脑梗塞的相关性进行初步研究,旨在为急性脑梗塞的临床预防提高一定的科学数据和临床参考.方法 随机抽取100例急性脑梗塞患者为ACI组,同期与ACI组患者年龄、性别以及生活习惯大致相同的健康体检者50人为对照组,留取5 ml空腹静脉血进行RFC-1的基因及血浆半胱氨酸检测.结果 ① ACI组中血浆Hcy水平较健康对照组显著性升高,其差异有统计学意义(P<0.05).根据对照组血浆Hcy水平的四分位数进行分级,结果显示随着血浆Hcy水平的升高,急性脑梗塞的危险逐渐增加,并呈现出一定的剂量效应关系.② 经Hardy-Weinberg平衡检验发现,RFC-1基因位点在两组中均无统计学意义(χ2=4.4288、0.11;P=0.6877、0.71).③ 两组RFC-1基因及等位基因频率比较,在ACI组中3种基因的频率依次为25 %、39 %及36 %,健康对照组依次为:40 %、42 %及18 %,两者相比具有统计学差异.等位基因频率的比较中也发现G出现显著高于A,具有统计学差异.④ 在RFC-1基因多态性与急性脑梗塞之间的关系分析中发现,携带GG基因型的者较携带AA型基因者患急性脑梗塞的风险显著升高(OR=2.95,95 % CI:1.25~6.05);而AG基因型对急性脑梗塞患者无影响.为了进一步分析,我们将AA和AG基因型者合并分析,结果发现携带GG基因者患急性脑梗塞的风险仍然升高2.15倍,但对急性脑梗塞患病危险无显著性差异.⑤ 血浆Hcy与RFC-1基因的交互作用和急性脑梗塞易感性的分析中发现,与Hcy正常且携带A等位基因者相比,RFC-1纯合突变者患有急性脑梗塞的危险升高3.69倍,单独高Hcy血症患者危险升高2.98倍,正常Hcy水平但携带GG型基因者风险升高3.17倍.在Logisitic回归模型中,Hcy与RFC-1的交互作用不明显.结论 ① RFC-1基因的80号位点A→G的突变可能对血浆同型半胱氨酸浓度产生影响.② RFC-1基因多态性与急性脑梗塞的易感性,改基因的纯合子突变大大增加了本病发生的风险.     

急性肾损伤早期诊断标志物的研究进展

急性肾损伤是由各种原因引起的短时间内肾功能急剧下降而出现的临床综合征,其概念是由急性肾衰发展而来。由于传统的AKI诊断标准缺乏特异性以及敏感性,因此,近年来许多新型AKI早期标志物引起研究者的重视。文章就几种新型标志物的生物学功能、研究现状及前景进行综述。     

血小板膜糖蛋白Ia基因807nt多态性与急性心肌梗死的关系研究

目的通过检测急性心肌梗死患者及对照人员的血小板膜糖蛋白（GP Ia）基因807nt多态性,探讨该多态性与急性心肌梗死发病的关系。方法血小板膜糖蛋白Ia基因807nt多态性分析：（1）碘化钾法提取人基因组DNA。（2）多聚酶链反应（PCR）扩增目的基因片段。（3）酶切产物经2%琼脂糖凝胶电泳分离后,紫外灯下检测酶切结果。（4）SPSS11.5软件分析数据。结果（1）急性心肌梗死组血小板膜糖蛋白Ia基因807nt处T等位基因频率显著高于对照组。（2）急性心肌梗死组血小板膜糖蛋白Ia基因807ntTT＋TC基因型频率显著高于对照组。（3）在血小板膜糖蛋白Ia基因807ntTT＋TC和CC基因型之间,高血压病和糠尿病的发病率无显著性差异。（4）在血小板膜糖蛋白Ia基因807nt TT＋TC和CC基因型之间,空腹血糖、血清甘油三脂浓度无显著性差异。（5）急性心肌梗死患者平均甘油三脂水平显著高于对照组。结论（1）血小板膜糖蛋白Ia基因807nt处T等位基因可能是急性心肌梗死发病的独立遗传性危险因素。（2）血小板膜糖蛋白Ia基因807nt多态性可能与高血压病、糖尿病的发病及糖代谢等无关。     

DNA修复基因多态性与肺癌易感性的研究进展

肺癌是目前世界上死亡率最高的恶性肿瘤,其发病率在世界范围内呈逐年上升趋势。研究表明,DNA修复基因多态性可通过影响机体对DNA损伤的修复能力而使机体罹患癌症的风险发生变化。本文介绍了相关DNA修复基因多态性的研究进展,并就其多态与肺癌易感性的关系作一系统的人群基因组流行病学研究综述。     

HLA-G基因多态性与疾病关联的研究进展

HLA-G是一种非经典的HLA-I类抗原,作为免疫耐受分子之一,它可通过多种机制参与机体免疫耐受的诱导与维持。大量的研究显示,HLA-G除表达于母胎界面外,在病理条件下HLA-G在周边组织也表达,例如病毒性感染、恶性肿瘤、自身免疫病和器官移植等。影响HLA-G表达的因素包括外源的(LPS、IL-10、IFN-γ等)和内源性(基因多态性等)。本文阐述的重点是HLA-G基因多态性与疾病的关联。     

Clinical features and outcomes of acute kidney injury among patients with acute hepatitis A

Background

Although acute hepatitis A is usually self-limited, the clinical manifestations can vary from mild to severe liver dysfunction. However, little is known about risk factors for and outcomes of acute kidney injury (AKI) in acute hepatitis A.

Objectives

To identify the risk factors for and outcomes of AKI in acute hepatitis A.

Study design

We identified 396 patients with acute hepatitis A, which registered between January 2006 and June 2009 at a tertiary care university hospital. Retrospective case-control studies were conducted in order to identify risk factors for AKI.

Results

Thirty patients (7.6%) developed AKI. On multivariate analysis, fulminant hepatitis, leukocytosis, and elevated CRP were independent risk factors for AKI associated with hepatitis A, and higher total bilirubin, leukocytosis, and elevated CRP were independent risk factor for AKI within nonfulminant hepatitis A. Of the 30 patients with AKI, 23 (76.7%) patients fully recovered, 2 patients maintained hemodialysis after hospital discharge and 5 patients died due to hepatic failure without recovery from AKI. Among 20 patients with AKI in nonfulminant subgroup, 19 patients (95%) recovered without hemodialysis.

Conclusions

AKI is not a rare complication of acute hepatitis A and severity of hepatitis and hepatic injury influence the development of AKI in acute hepatitis A.     

65例老年慢性肾脏病基础上急性肾损伤的临床观察

目的 分析老年慢性肾脏病基础上急性肾损伤(A/C)的基础疾病、发病诱因及影响预后的危险因素.方法 回顾性分析2005年12月至2009年12月于本院住院治疗的65例老年A/C患者的临床资料,分析A/C患者的基础疾病、发病诱因及影响预后的危险因素.根据治疗后肾功能恢复情况将患者分为2组:肾功能恢复患者和肾功能部分恢复患者合并为肾功能恢复组,肾功能未恢复患者与死亡患者合并为肾功能未恢复组,比较两组患者的少尿持续时间、入院时血清白蛋白水平和最高血清肌酐(Scr)水平.结果 糖尿病肾病是老年A/C患者的主要基础疾病(38.5％,25/65),药物因素(30.8％,20/65)和严重感染(27.7％,l8/65)是老年A/C患者的主要发病诱因.与肾功能恢复组比较,肾功能未恢复组患者少尿持续时间较长[(1 1.5±3.4)d比(4.2±1.8)d,P＜0.05]、入院时血清白蛋白水平较低[(23.6±3.1)g/L比(26.6± 4.5) g/L,P＜0.05],而最高Scr水平较高[(601.2± 142.7) μmol/L比(421.3±107.3) μmol/L,P＜0.05].结论 老年A/C患者应对其基础疾病进行有效治疗,积极消除发痫诱因和控制影响预后的危险因素.     

Impact of acute kidney injury on clinical outcomes after ST elevation acute myocardial infarction

Purpose

This study aimed to compare the incidence and clinical significance of transient versus persistent acute kidney injury (AKI) on acute ST elevation myocardial infarction (STEMI).

Materials and Methods

The study was a retrospective cohort of 855 patients with STEMI. AKI was defined as an increase of ≥0.3 mg/dL in creatinine level at any point during hospital stay. The study population was classified into 5 groups: 1) patients without AKI; 2) patients with mild AKI that was resolved by discharge (creatinine change less than 0.5mg/dL compared with admission creatinine during hospital stay, transient mild AKI); 3) patients with mild AKI that did not resolve by discharge (persistent mild AKI); 4) patients with moderate/severe AKI that was resolved by discharge (creatinine change more than 0.5 mg/dL compared with admission creatinine, transient moderate/severe AKI); 5) patients with moderate/severe AKI that did not resolve by discharge (persistent moderate/severe AKI). We investigated 1-year all-cause mortality after hospital discharge for the primary outcome of the study. The relation between AKI and 1-year mortality after STEMI was analyzed.

Results

AKI occurred in 74 (8.7%) patients during hospital stay. Adjusted hazard ratio for mortality was 3.139 (95% CI 0.764 to 12.897, p=0.113) in patients with transient, mild AKI, and 8.885 (95% CI 2.710 to 29.128, p<0.001) in patients with transient, moderate/severe AKI compared to patients without AKI. Persistent moderate/severe AKI was also independent predictor of 1 year mortality (hazard ratio, 5.885; 95% CI 1.079 to 32.101, p=0.041).

Conclusion

Transient and persistent moderate/severe AKI during acute myocardial infarction is strongly related to 1-year all cause mortality after STEMI.     

重度窒息新生儿发生急性肾损伤回顾性分析

目的探讨重度窒息新生儿中急性肾损伤（AKI）的发生情况及其诊断标准的适用性。方法回顾性分析2005年1月至2009年12月于北京大学第一医院住院的重度窒息新生儿。根据2005年急性肾损伤协作网提出的AKI诊断标准（包括尿量标准和SCr标准）,将入选患儿分为AKI组和无AKI组。采集患儿一般资料、围生期资料、肾脏损伤情况、治疗和近期预后情况。结果最终纳入患儿30例,AKI组17例,无AKI组13例。①AKI组10/17例仅符合尿量标准,而不符合SCr升高标准,按AKI分期标准分为1期4例、2期5例、3期1例;7/17例同时符合尿量标准和SCr标准,其中3例按照SCr标准和尿量标准分期相同（均为1期）,1例按照SCr标准分期为2期的患儿符合尿量标准1期,余3例按尿量标准分期高于SCr标准。7/17例有SCr一过性升高（SCr〉133μmol.L-1）,达到急性肾功能衰竭诊断标准。②AKI组和无AKI组平均住院时间分别为（14.7±13.9）和（13.7±9.6）d,两组差异无统计学意义（P=0.83）。AKI组预后不良5/17例（29.4%）,包括死亡1例（同时符合尿量标准和SCr标准）,放弃治疗4例（3例同时符合尿量标准和SCr标准,1例仅符合尿量标准）;无AKI组预后不良2/13例（15.4%）,均为死亡病例（均仅符合尿量标准）,两组差异无统计学意义（P=0.368）。按照SCr升高标准,符合AKI诊断的4/7例（57.1%）患儿预后不良,不符合SCr升高标准的3/23例（13.0%）患儿预后不良,差异有统计学意义（P=0.016）。结论在重度窒息新生儿中存在AKI的病例。SCr升高可能提示预后不良,但由于样本量小,无长期随访资料,目前尚不能评价SCr和尿量是否为诊断新生儿AKI的最适宜指标。     

Septic acute kidney injury in critically ill Indian patients

Acute kidney injury (AKI) is an independent variable for poor outcome in critically ill patients. The pathophysiology of septic AKI is distinct from that of non-septic AKI. We studied the clinical profile and outcome of septic AKI since such data is sparse in Indian patients. In this single-center retrospective, observational, cohort study, septic AKI has been found with high incidence (31%) and overall mortality was 52%. Age, number of non-renal organ failure, and APACHE II score were found as significant predictors of outcome in this population.     

大鼠急性肾损伤导致肝细胞凋亡的实验研究

 目的：观察大鼠急性肾损伤（AKI）引起肝细胞凋亡的细胞学特点。方法：建立AKI（包括缺血性和非缺血性）大鼠模型后应用免疫印迹法、免疫组织化学染色法和光学、电子显微镜技术对AKI大鼠的肾脏和肝脏进行观察。结果：(1) 缺血性AKI 肾小管出现了大面积细胞坏死和细胞凋亡的表现。不论是缺血性还是非缺血性AKI的动物都发生了急性肾功能损伤和急性肝功能受损。(2) 免疫印迹法测定结果显示AKI动物肝脏的肿瘤坏死因子受体α（TNFRα）和半胱氨酸天冬氨酸蛋白酶-3（caspase-3）蛋白表达增强。从caspase-3免疫组化染色的结果可以看出阳性细胞均出现在AKI动物肝脏内。(3) 电子显微镜观察发现AKI动物肝脏中确有细胞凋亡和副凋亡的表现。(4) 缺血性与非缺血性AKI诱导肝细胞凋亡的表现相同。结论：AKI可引起肝细胞凋亡和副凋亡,其中经TNFRα启动的caspase依赖的细胞死亡构成了AKI引起的肝细胞凋亡。这种肝细胞凋亡是由肾功能损伤导致的血尿毒物质引起的。     

Pediatric acute kidney injury: A syndrome under paradigm shift

The recent standardization and validation of definitions of pediatric acute kidney injury (pAKI) has ignited new dimensions of pAKI epidemiology and its risk factors. pAKI causes increased morbidity and mortality in critically ill-children. Among the hospitalized patients incidence of pAKI ranges from 1% to 31%, while mortality ranges from 28% to 82%, presenting a broad range due to lack of uniformly acceptable pAKI definition. In addition, cumulative data regarding the progression of pAKI to chronic kidney disease in children is rising. Despite these alarming figures, treatment modalities have failed to deliver significantly. In this review, we will summarize the latest developments of pAKI and highlight important aspects of pAKI management.     

Iron,ferroptosis, and new insights for prevention in acute kidney injury

Acute kidney injury (AKI) is a very common condition with high morbidity and mortality, which can be seen in 5–7% of all hospitalized patients and in up to 57% of all intensive care unit admissions. Despite recent advances in clinical care, the prevalence of AKI has been shown to increase with virtually no change in mortality. AKI is a complex syndrome occurring in a variety of clinical settings. Early detection is crucial to prevent irreversible loss of renal function. The pathogenesis of AKI is highly multifactorial and complex, including vasoconstriction, reactive oxygen species formation, cell death, abnormal immune modulators and growth factors. Emerging evidence from both human and animal studies suggests that dysregulation of iron metabolism may play a potentially important role in AKI. Therefore, targeting the iron homeostasis may provide a new therapeutic intervention for AKI. New therapeutic strategies including iron chelation therapy, targeting iron metabolism related proteins and direct inhibitors of ferroptosis are imperative to improve the outcomes of patients. Taking into consideration the complexity of AKI, one intervention may not be enough for therapeutic success. Future preclinical studies in animal disease models followed by well-designed clinical trials should be conducted to extend findings from animal AKI models to humans.     

Nestin+ kidney resident mesenchymal stem cells for the treatment of acute kidney ischemia injury

Renal resident mesenchymal stem cells (MSCs) are important regulators of kidney homeostasis, repair or regeneration. However, natural distribution and the starting population properties of these cells remain elusive because of the lack of specific markers. Here, we identified post-natal kidney derived Nestin⁺ cells that fulfilled all of the criteria as a mesenchymal stem cell. These isolated Nestin⁺ cells expressed the typical cell-surface marker of MSC, including Sca-1, CD44, CD106, NG2 and PDGFR-α. They were capable of self-renewal, possessed high clonogenic potential and extensive proliferation for more than 30 passages. Under appropriate differentiation conditions, these cells could differentiate into adipocytes, osteocytes, chondrocytes and podocytes. After intravenous injection into acute kidney injury mice, Nestin⁺ cells contributed to functional improvement by significantly decreasing the peak level of serum creatinine and BUN, and reducing the damaged cell apoptosis. Furthermore, conditioned medium from Nestin⁺ cells could protect against ischemic acute renal failure partially through paracrine factor VEGF. Taken together, our findings indicate that renal resident Nestin⁺ MSCs can be derived, propagated, differentiated, and repair the acute kidney injury, which may shed new light on understanding MSCs biology and developing cell replacement therapies for kidney disease.