Obesity-related glomerulopathy: insights from gene expression profiles of the glomeruli derived from renal biopsy samples

Obesity-related glomerulopathy (ORG) is an important complication of obesity. The pathophysiological mechanism of glomerular injury in ORG is incompletely understood. Gene expression profiles in the glomeruli obtained from renal biopsy samples of patients with ORG were investigated, using a microdissection technique combined with Affymetrix microarray analysis. Six patients presented with obesity, proteinuria, and biopsy-proven ORG were enrolled. Two sex- and age-matched donor kidneys were applied as the controls. Glomeruli were dissected out from renal biopsy samples under microscope, and total RNA was extracted using RNeasy Micro kit. After two rounds of T7 promoter-based RNA amplification, gene expression profiles of the glomeruli samples were detected using Affymetrix U133A gene chips. Bioinformatic tools were applied to analyze the microarray data. Results of candidate ORG-related genes were further confirmed by real-time quantitative PCR and immunohistochemistry staining using renal biopsy samples of a larger pool of 15 ORG patients. Genes related to lipid metabolism, inflammatory cytokines, and insulin resistance were the most highlighted subgroups that significantly changed in the glomerular gene expression profiles of the ORG patients, compared with the controls. The expression levels of several key genes in lipid metabolism were increased over 2-fold, including low-density lipoprotein receptor, fatty acid binding protein 3, and sterol regulatory element binding protein 1. Moreover, some inflammatory cytokines and their downstream molecules were increased as well, including TNF-alpha and its receptors, IL-6 signal transducer, and interferon-gamma. As the indicators of insulin resistance in the local glomerular cells, levels of glucose-transporter 1, leptin receptor, peroxisome proliferator-activated receptor-gamma, and vascular endothelial growth factor increased, too. In addition to lipid dysmetabolism and insulin resistance, the activation of an inflammatory process in the glomeruli might play a unique role in the development of obesity-related glomerulopathy. Our results expand the understanding of obesity-induced glomerular injuries and shed light on new approaches in the treatment of this disease.     

Assessment of health-related quality of life in Chinese patients with minimal hepatic encephalopathy

AIM:To evaluate the health-related quality of life (HRQOL) based on the Chinese version of SF-36 and Chronic Liver Disease Questionnaire (CLDQ) in subjects with chronic hepatitis B,liver cirrhosis,including patients with minimal hepatic encephalopathy (MHE). METHODS:The SF-36 and CLDQ were administered to 160 healthy volunteers,20 subjects with chronic hepatitis B and 106 patients with cirrhosis (33 cases exhibited MHE). HRQOL scores were compared among the different study groups. The SF-36 includes eight health concepts:physical functioning,role-physical,body pain,general health,vitality,social functioning,role-emotion,and mental health. Six domains of CLDQ were assessed:abdominal symptoms,fatigue,systemic symptoms,activity,emotional function and worry. RESULTS:Compared with healthy controls (96.9 ± 4.5,86.6 ± 18.4,90.1 ± 12.5,89.0 ± 5.7,87.5 ± 4.3,95.8 ± 7.1,88.5 ± 15.9,88.7 ± 5.2 in SF-36 and 6.7 ± 0.5,6.1 ± 0.6,6.3 ± 0.6,6.5 ± 0.5,6.3 ± 0.5,6.8 ± 0.4 in CLDQ),patients with chronic hepatitis B (86.3 ± 11.0,68.8 ± 21.3,78.9 ± 14.4,60.8 ± 10.5,70.8 ± 8.6,76.1 ± 12.6,50.0 ± 22.9,72.2 ± 10.6 and 5.5 ± 1.0,4.5 ± 1.0,5.2 ± 1.1,5.3 ± 0.9,4.8 ± 0.9,4.9 ± 1.0) and cirrhosis (52.8 ± 17.4,32.8 ± 27.9,61.6 ± 18.9,30.2 ± 18.3,47.9 ± 20.1,54.0 ± 19.2,28.9 ± 26.1,51.1 ± 17.8 and 4.7 ± 1.2,3.9 ± 1.2,4.7 ± 1.2,4.7 ± 1.3,4.7 ± 1.0,4.4 ± 1.1) had lower HRQOL on all scales of the SF-36 and CLDQ (P < 0.01 for all). Increasing severity of liver cirrhosis (based on the Child-Pugh score/presence or absence of MHE) was associated with a decrease in most components of SF-36 and CLDQ,especially SF-36.CONCLUSION:The Chinese version of SF-36 along with CLDQ is a valid and reliable method for testing MHE in patients with liver cirrhosis. Cirrhosis and MHE are associated with decreased HRQOL.     

Ten-year cardiovascular disease risk of metabolic syndrome without central obesity in middle-aged chinese

This study aimed to examine the relation between central obesity and other metabolic disorders of metabolic syndrome (MS) and compare the long-term risks of cardiovascular disease (CVD) between patients with MS with or without central obesity in middle-aged Chinese. The study included 30,378 Chinese aged 35 to 64 years at baseline with complete measurements for MS components and follow-up data for new acute CVD events from 1992 to 2003. The 10-year relative and absolute CVD risks in the MS groups with or without central obesity were compared. Results showed that 78% of patients with MS had central obesity and 22% with MS had no central obesity, diagnosed using updated Adult Treatment Panel III criteria with cut-off values appropriate for Asian populations. Central obesity, as well as other metabolic disorders in patients with MS, except for increased triglycerides, increased CVD risk significantly. There were no significant differences in 10-year absolute and relative risks of coronary heart disease events and ischemic CVD events between the 2 MS groups. In conclusion, MS with or without central obesity has a significantly increased 10-year risk of CVD in middle-aged Chinese.     

EGFR和HER2联合过度表达在食管癌中的意义

目的：分析EGFR和HER2的联合过度表达在食管癌发生发展过程中的作用及与预后的关系。方法：采用免疫组化技术，检测45例食管癌根治术患者肿瘤组织中EGFR和HER2的表达。结果：在食管癌中EGFR和HER2的联合过度表达率为25％。EGFR和HER2联合过度表达与食管癌的分化程度和肿瘤的局部浸润程度无关，在N。期患者中两者的联合过度表达高于N0期患者。联合过度表达者的预后较差。结论：EGFR和HER2联合过度表达在食管癌转移方面可能起着重要的作用，属于肿瘤发生发展、演进过程中的后期事件。EGFR和HER2联合过度表达提示预后不良。     

Combination of Cobe AutoPBSC and Gambro Elutra as a platform for monocyte enrichment in dendritic cell (DC) therapy: clinical study

Monocytes are a common source for generating dendritic cells (DCs). The aim of the present study was to evaluate the efficiency of a platform for monocyte collection and enrichment in a clinical setting. The platform was based on the combination of two semiautomated devices; the Cobe Spectra Auto PBSC for mononuclear cells (MNC) collection followed by counterflow elutriation for monocyte enrichment (Gambro BCT Elutra). Twenty-four patients with various types of epithelial cancer participated in the study. MNC collections were first performed as large volume leukapheresis (LVL). Subsequently, MNC products were processed with an elutriation system for monocyte isolation. LVL resulted in the collection of MNC at a median of 8.1 x 10(9) cells, containing of 31.4% monocytes. A similar efficacy was also shown in patients with lower peripheral blood counts. Elutriation of the MNC product with the Cobe Elutra device resulted in the enrichment of monocytes at a median of 2.7 x 10(9) cells, with a recovery of 80.2% and a purity of 90.7%. These monocytes were then successfully developed into DCs for clinical therapy after in vitro manipulation. These data suggest that the combination of the Cobe Spectra Auto PBSC and the Gambro BCT Elutra is an effective platform for monocyte enrichment in clinical practice according to GCP standards and GMP guidelines, and can be easily implemented in the clinical routine under current DC protocols.     

去铁胺单独及联合三氧化二砷对裸鼠HL-60细胞移植瘤的抑制作用及其可能机制

目的 探讨去铁胺(DFO)单独及联合三氧化二砷(As2O3)对裸鼠HL-60白血病细胞移植瘤的抑制作用及机制,为临床采用铁螯合剂治疗或辅助治疗白血病提供实验依据.方法 用高致瘤性HL-60细胞建立裸鼠皮下移植瘤模型,随机分为4组:50 mg/kg DFO单药组、3 mg/kg As2O3单药组、联合用药组(50 mg/...     

不同穴位重复电针预处理诱导兔脊髓缺血耐受效果的对比

目的:比较不同穴位电针预处理对兔脊髓缺血再灌注损伤保护作用的效果,为临床提供最佳的预处理方案。方法:32只雄性新西兰大白兔随机数字表法分成4组(各组n=8),即对照组、戊巴比妥钠组、委中穴组及足三里穴组。对照组静脉给予生理盐水1mL/kg,连续5d;戊巴比妥钠组静脉给予戊巴比妥钠30mg/kg,连续5d;委中穴和足三里穴组每天在戊巴比妥钠(30mg/kg)麻醉下,电针分别刺激委中穴和足三里穴60min/d,连续5d。最后一次预处理后24h,夹闭肾下腹主动脉20min,制作兔脊髓缺血模型;再灌注后4,8,12,24和48h分别对动物后肢运动功能评分;再灌注48h后,深麻醉下处死动物取脊髓(L5～7),制作标本行组织病理学观察。结果:所有动物均存活,再灌注后48h电针预处理委中穴和足三里穴组后肢运动功能评分及脊髓前角运动神经元计数均明显高于对照组(P=0.001);足三里组后肢运动功能评分和脊髓前角运动神经元计数明显低于委中穴组(P=0.001);对照组与戊巴比妥钠组相比,后肢运动功能评分及脊髓前角神经元计数无显著性差别(P=1.0和P=0.873)。结论:电针预处理对兔脊髓缺血再灌注损伤有显著的保护作用,且刺激委中穴优于刺激足三里穴的效果。     

烧伤病人体温研究现状

对烧伤病人体温变化的过程、体温变化的原因、体温监测等方面进行了综述,并提出处理体温异常的几种方法。     

Altered spinal arachidonic acid turnover after peripheral nerve injury regulates regional glutamate concentration and neuropathic pain behaviors in rats

Spinal glutamate transporters (GT) have been implicated in the mechanisms of neuropathic pain; however, how spinal GT uptake activity is regulated remains unclear. Here we show that alteration of spinal arachidonic acid (AA) turnover after peripheral nerve injury regulated regional GT uptake activity and glutamate homeostasis. Chronic constriction nerve injury (CCI) in rats significantly reduced spinal GT uptake activity ((3)H-glutamate uptake) with an associated increase in extracellular AA and glutamate concentration from spinal microdialysates on postoperative day 8. AACOCF3 (a cytosolic phospholipase A2 inhibitor, 30mug) given intrathecally twice a day for postoperative day 1-7 reversed this CCI-induced spinal AA production, prevented the reduced spinal GT uptake activity and increased extracellular glutamate concentration. Conversely, alteration of spinal AA metabolism by diclofenac (a cyclooxygenase 1/2 inhibitor, 200mug) further reduced spinal GT uptake activity and increased extracellular glutamate concentration in CCI rats. GT uptake activity was also attenuated when AA (10 or 100nM) was directly added into spinal samples of na?ve rats in an in vitro(3)H-glutamate uptake assay, indicating a direct inhibitory effect of AA on GT uptake activity. Consistent with these findings, AACOCF3 reduced the development of both thermal hyperalgesia and mechanical allodynia, whereas diclofenac exacerbated thermal hyperalgesia, in CCI rats. Thus, spinal AA turnover may serve as a regulator in CCI-induced changes in regional GT uptake activity, glutamate homeostasis, and neuropathic pain behaviors. These data suggest that regulating spinal AA turnover may be a useful approach to improving the clinical management of neuropathic pain.