The development of formulas estimating glomerular filtration rate(eG FR) from serum creatinine and cystatin C and accounting for certain variables affecting the production rate of these biomarkers, including ethnicity...The development of formulas estimating glomerular filtration rate(eG FR) from serum creatinine and cystatin C and accounting for certain variables affecting the production rate of these biomarkers, including ethnicity, gender and age, has led to the current scheme of diagnosing and staging chronic kidney disease(CKD),which is based on e GFR values and albuminuria.This scheme has been applied extensively in various populations and has led to the current estimates of prevalence of CKD. In addition, this scheme is applied in clinical studies evaluating the risks of CKD and the efficacy of various interventions directed towards improving its course. Disagreements between creatinine-based and cystatin-based e GFR values and between e GFR values and measured GFR have been reported in various cohorts. These disagreements are the consequence of variations in the rate of production and in factors, other than GFR, affecting the rate of removal of creatinine and cystatin C. The disagreements create limitations for all e GFR formulas developed so far. The main limitations are low sensitivity in detecting early CKD in several subjects, e.g., those with hyperfiltration, and poor prediction of the course of CKD. Research efforts in CKD are currently directed towards identification of biomarkers that are better indices of GFR than the current biomarkers and,particularly, biomarkers of early renal tissue injury.展开更多
目的:探讨成人和儿童术前乳酸林格氏液液体动力学的差别。方法:本研究是随机,双盲前瞻性研究。择期盆腔、肛肠或者下肢小手术患者28例,美国麻醉医师协会(ASA)I级,其中儿童14例,成人14例。所有患者给予镇静药后在20 min内恒速输入10 m L...目的:探讨成人和儿童术前乳酸林格氏液液体动力学的差别。方法:本研究是随机,双盲前瞻性研究。择期盆腔、肛肠或者下肢小手术患者28例,美国麻醉医师协会(ASA)I级,其中儿童14例,成人14例。所有患者给予镇静药后在20 min内恒速输入10 m L/kg的乳酸林格氏液体,通过血红蛋白(Hb)稀释-时间曲线和尿量采用Matlab 4.2软件包计算液体动力学参数。结果:一级动力学模型拟合结果显示,与成人相比,在输入林格氏液体后90 min内儿童的血浆稀释程度明显降低(0.16 vs 0.07,P=0.000),儿童将输入液体的43%通过肾脏排出,显著高于成人(18%)(P=0.011)。按公斤体重计算儿童和成人对乳酸林格氏液的血浆清除率分别是2.2 m L·min-1·kg-1和0.5 m L·min-1·kg-1(P=0.016),而肾脏对乳酸林格氏液体的清除率两组分别是0.76 m L·min-1·kg-1和0.10 m L·min-1·kg-1,(P=0.000)。结论:儿童对乳酸林格氏液体血浆和肾脏清除率分别是成人的4倍和7倍,术前给儿童输液,按照体重计算量可以参照成人的剂量。展开更多
A major clinical translational challenge in nanomedicine is the potential of toxicity associated with the uptake and long-term retention of non-degradable nanoparticles （NPs） in major organs. The development of inor...A major clinical translational challenge in nanomedicine is the potential of toxicity associated with the uptake and long-term retention of non-degradable nanoparticles （NPs） in major organs. The development of inorganic NPs that undergo renal clearance could potentially resolve this significant biosafety concern. However, it remains unclear whether inorganic NPs that can be excreted by the kidneys remain capable of targeting tumors with poor permeability. Glioblastoma multiforme, the most malignant orthotopic brain tumor, presents a unique challenge for NP delivery because of the blood-brain barrier and robust blood-tumor barrier of reactive microglia and macroglia in the tumor microenvironment. Herein, we used an orthotopic murine glioma model to investigate the passive targeting of glutathione-coated gold nanoparticles （AuNPs） of 3 nm in diameter that undergo renal clearance and 18-nm AuNPs that fail to undergo renal clearance. Remarkably, we report that 3-nm AuNPs were able to target intracranial tumor tissues with higher efficiency （2.3× relative to surrounding non-tumor normal brain tissues） and greater specificity （3.0×） than did the larger AuNPs. Pharmacokinetics studies suggested that the higher glioma targeting ability of the 3-nm AuNPs may be attributed to the longer retention time in circulation. The total accumulation of the 3-nm AuNPs in major organs was significantly less （8.4×） than that of the 18-nm AuNPs. Microscopic imaging of blood vessels and renal-clearable AuNPs showed extravasation of NPs from the leaky blood-tumor barrier into the tumor interstitium. Taken together, our results suggest that the 3-nm AuNPs, characterized by enhanced permeability and retention, are able to target brain tumors and undergo renal clearance.展开更多
The timing of renal replacement therapy for patients with end-stage renal disease has been subject to considerable variation. The United States Renal Data System shows an ascending trend of early dialysis initiation u...The timing of renal replacement therapy for patients with end-stage renal disease has been subject to considerable variation. The United States Renal Data System shows an ascending trend of early dialysis initiation until 2010, at which point it decreased slightly for the following 2 years. In the 1990s, nephrologists believed that early initiation of dialysis could improve patient survival. Based on the Canadian-United States Peritoneal Dialysis study, the National Kidney Foundation Dialysis Outcomes Quality Initiative recommended that dialysis should be initiated early. Since 2001, several observational studies and 1 randomized controlled trial have found no beneficial effect when patients were placed on dialysis early. In contrast, they found that an increase in mortality was associated with early dialysis initiation. The most recent dialysis initiation guidelines recommend that dialysis should be initiated at an estimated glomerular filtration rate （eGFR） of greater than or equal to 6 mL/min per 1.73 m2. Nevertheless, the decision to start dialysis is mainly based on a predefned eGFR value, and no convincing evidence has demonstrated that patients would benefit from early dialysis initiation as indicated by the eGFR. Even today, the optimal dialysis initiation time remains unknown. The decision of when to start dialysis should be based on careful clinical evaluation.展开更多
Plasmonic Pd nanosheets have been emerging as promising materials for application in near-infrared(NIR) photothermal therapy(PTT) of cancer. However, animal in mice studies indicated that the original synthesized poly...Plasmonic Pd nanosheets have been emerging as promising materials for application in near-infrared(NIR) photothermal therapy(PTT) of cancer. However, animal in mice studies indicated that the original synthesized poly(vinylpyrrolidone)(PVP)-protected small Pd nanosheets(Pd-PVP) and some further surface-modified small Pd nanosheets such as Pd-PEG(SH) easily accumulated in reticuloendothelial system(RES) organs(liver, spleen, etc.) and were difficult to be cleared from these organs quickly. In the work, we surprisingly found that glutathione(GSH) could promote the clearance of surface-modified small Pd nanosheets(e.g. Pd-PVP, Pd-PEG(SH) and Pd-GSH) from the RES organs efficiently. The effects of GSH on the biodistribution and clearance of different surface-modified Pd nanosheets were investigated. Our results indicated that these surface-modified Pd nanosheets with or without GSH added caused no morbidity at target primary organs, and GSH can promote the clearance of different surface-modified Pd nanosheets in the order of Pd-PVP≈Pd-PEG(SH)>Pd-GSH. This study suggests that glutathione could be an attractive reagent for promoting nanomaterials eliminated from the reticuloendothelial systems(RES).展开更多
基金the Research Service of the Raymond G. Murphy VA Medical Center for its support of this work
文摘The development of formulas estimating glomerular filtration rate(eG FR) from serum creatinine and cystatin C and accounting for certain variables affecting the production rate of these biomarkers, including ethnicity, gender and age, has led to the current scheme of diagnosing and staging chronic kidney disease(CKD),which is based on e GFR values and albuminuria.This scheme has been applied extensively in various populations and has led to the current estimates of prevalence of CKD. In addition, this scheme is applied in clinical studies evaluating the risks of CKD and the efficacy of various interventions directed towards improving its course. Disagreements between creatinine-based and cystatin-based e GFR values and between e GFR values and measured GFR have been reported in various cohorts. These disagreements are the consequence of variations in the rate of production and in factors, other than GFR, affecting the rate of removal of creatinine and cystatin C. The disagreements create limitations for all e GFR formulas developed so far. The main limitations are low sensitivity in detecting early CKD in several subjects, e.g., those with hyperfiltration, and poor prediction of the course of CKD. Research efforts in CKD are currently directed towards identification of biomarkers that are better indices of GFR than the current biomarkers and,particularly, biomarkers of early renal tissue injury.
文摘目的:探讨成人和儿童术前乳酸林格氏液液体动力学的差别。方法:本研究是随机,双盲前瞻性研究。择期盆腔、肛肠或者下肢小手术患者28例,美国麻醉医师协会(ASA)I级,其中儿童14例,成人14例。所有患者给予镇静药后在20 min内恒速输入10 m L/kg的乳酸林格氏液体,通过血红蛋白(Hb)稀释-时间曲线和尿量采用Matlab 4.2软件包计算液体动力学参数。结果:一级动力学模型拟合结果显示,与成人相比,在输入林格氏液体后90 min内儿童的血浆稀释程度明显降低(0.16 vs 0.07,P=0.000),儿童将输入液体的43%通过肾脏排出,显著高于成人(18%)(P=0.011)。按公斤体重计算儿童和成人对乳酸林格氏液的血浆清除率分别是2.2 m L·min-1·kg-1和0.5 m L·min-1·kg-1(P=0.016),而肾脏对乳酸林格氏液体的清除率两组分别是0.76 m L·min-1·kg-1和0.10 m L·min-1·kg-1,(P=0.000)。结论:儿童对乳酸林格氏液体血浆和肾脏清除率分别是成人的4倍和7倍,术前给儿童输液,按照体重计算量可以参照成人的剂量。
文摘A major clinical translational challenge in nanomedicine is the potential of toxicity associated with the uptake and long-term retention of non-degradable nanoparticles （NPs） in major organs. The development of inorganic NPs that undergo renal clearance could potentially resolve this significant biosafety concern. However, it remains unclear whether inorganic NPs that can be excreted by the kidneys remain capable of targeting tumors with poor permeability. Glioblastoma multiforme, the most malignant orthotopic brain tumor, presents a unique challenge for NP delivery because of the blood-brain barrier and robust blood-tumor barrier of reactive microglia and macroglia in the tumor microenvironment. Herein, we used an orthotopic murine glioma model to investigate the passive targeting of glutathione-coated gold nanoparticles （AuNPs） of 3 nm in diameter that undergo renal clearance and 18-nm AuNPs that fail to undergo renal clearance. Remarkably, we report that 3-nm AuNPs were able to target intracranial tumor tissues with higher efficiency （2.3× relative to surrounding non-tumor normal brain tissues） and greater specificity （3.0×） than did the larger AuNPs. Pharmacokinetics studies suggested that the higher glioma targeting ability of the 3-nm AuNPs may be attributed to the longer retention time in circulation. The total accumulation of the 3-nm AuNPs in major organs was significantly less （8.4×） than that of the 18-nm AuNPs. Microscopic imaging of blood vessels and renal-clearable AuNPs showed extravasation of NPs from the leaky blood-tumor barrier into the tumor interstitium. Taken together, our results suggest that the 3-nm AuNPs, characterized by enhanced permeability and retention, are able to target brain tumors and undergo renal clearance.
基金Supported by 201502010 from the Public welfare project of National Health and Family Planning Commission of the People's Republic of China
文摘The timing of renal replacement therapy for patients with end-stage renal disease has been subject to considerable variation. The United States Renal Data System shows an ascending trend of early dialysis initiation until 2010, at which point it decreased slightly for the following 2 years. In the 1990s, nephrologists believed that early initiation of dialysis could improve patient survival. Based on the Canadian-United States Peritoneal Dialysis study, the National Kidney Foundation Dialysis Outcomes Quality Initiative recommended that dialysis should be initiated early. Since 2001, several observational studies and 1 randomized controlled trial have found no beneficial effect when patients were placed on dialysis early. In contrast, they found that an increase in mortality was associated with early dialysis initiation. The most recent dialysis initiation guidelines recommend that dialysis should be initiated at an estimated glomerular filtration rate （eGFR） of greater than or equal to 6 mL/min per 1.73 m2. Nevertheless, the decision to start dialysis is mainly based on a predefned eGFR value, and no convincing evidence has demonstrated that patients would benefit from early dialysis initiation as indicated by the eGFR. Even today, the optimal dialysis initiation time remains unknown. The decision of when to start dialysis should be based on careful clinical evaluation.
基金supported by the National Natural Science Foundation of China(21101131)the National Basic Research Program of China(2014CB932004)+2 种基金the Natural Science Foundation of Fujian Province(2012J01056)the Fundamental Research Funds for the Central Universities(2010121015)the open project grant from State Key Laboratory of Chemo/biosensing and Chemometrics(2013009)
文摘Plasmonic Pd nanosheets have been emerging as promising materials for application in near-infrared(NIR) photothermal therapy(PTT) of cancer. However, animal in mice studies indicated that the original synthesized poly(vinylpyrrolidone)(PVP)-protected small Pd nanosheets(Pd-PVP) and some further surface-modified small Pd nanosheets such as Pd-PEG(SH) easily accumulated in reticuloendothelial system(RES) organs(liver, spleen, etc.) and were difficult to be cleared from these organs quickly. In the work, we surprisingly found that glutathione(GSH) could promote the clearance of surface-modified small Pd nanosheets(e.g. Pd-PVP, Pd-PEG(SH) and Pd-GSH) from the RES organs efficiently. The effects of GSH on the biodistribution and clearance of different surface-modified Pd nanosheets were investigated. Our results indicated that these surface-modified Pd nanosheets with or without GSH added caused no morbidity at target primary organs, and GSH can promote the clearance of different surface-modified Pd nanosheets in the order of Pd-PVP≈Pd-PEG(SH)>Pd-GSH. This study suggests that glutathione could be an attractive reagent for promoting nanomaterials eliminated from the reticuloendothelial systems(RES).
