Hypertension(HTN)and type 2 diabetes mellitus(T2DM)are interconnected metabolic diseases[1,2]that considerably increase susceptibility to microvascular and macrovascular disorders.In many patients,HTN and diabetes com...Hypertension(HTN)and type 2 diabetes mellitus(T2DM)are interconnected metabolic diseases[1,2]that considerably increase susceptibility to microvascular and macrovascular disorders.In many patients,HTN and diabetes comorbidity(HDC)is caused by mutual pathogenic pathways,such as endothelial dysfunction,atherosclerosis,oxidative stress,and vascular inflammation[1].Hence.展开更多
Objective:To investigate the efficiency ofβ-galactosidase gene transfer into rat kidney with ultrasound-mediated microbubble destruction via different injection routes.Methods:A total of 25 Wistar rats were randomly ...Objective:To investigate the efficiency ofβ-galactosidase gene transfer into rat kidney with ultrasound-mediated microbubble destruction via different injection routes.Methods:A total of 25 Wistar rats were randomly divided into 5 groups.Four groups received a mixture of optison microbubbles(0.2 mL) and lacz plasmids(25μg) injection via renal artery,tail vein,anterior tibial muscle and renal parenchyma,respectively.The control group received a mixture of PBS (xx mL) and lacz plasmids(25μg) via renal artery.Three days after the gene transfer,ultrasound with fixed frequency and power(1 MHz,xxW) was delivered to the kidneys for 3 min.The efficiency of the gene transfer and expression was evaluated on the basis ofβ-galactosidase expression.The side effects of this method were evaluated by immunohistological method. Results:β-galactosidase expression could be observed only in tubules but not in glomeruli and interstitial area.The efficiency of renal artery group was higher than that of tail vein,anterior tibial muscle and renal parenchyma group(P【0.05).Immunohistochemical analysis revealed co-expression ofβ-galactosidase with a roximal tubule marker,megalin,which suggested that ultrasound enhanced gene transfer into the proximal tubular epithelial cells.Noβ-galactosidase expression was observed in the extrarenal organs.There were no evident pathological and biochemical changes after gene transfer.Conclusions:Ultrasound-mediated microbubble destruction can transfer gene into kidney via renal artery,tail vein,anterior tibial muscle and renal parenchyma.Compared with renal artery,administrating microbubbles via tail vein and anterior tibial muscle are more convenient and less vulnerarious.展开更多
Objective: We prospectively investigated 121 renal allograft biopsy specimens performed in our center. Methods: BKVAN was diagnosed by light microscopic examination and a positive immunohistochemistry staining of anti...Objective: We prospectively investigated 121 renal allograft biopsy specimens performed in our center. Methods: BKVAN was diagnosed by light microscopic examination and a positive immunohistochemistry staining of anti-SV40 large T antibody in a biopsy specimen. Results: Of the 121 patients, nine were diagnosed with BKVAN (7.4%). Nine patients whith BKVN classically presents as allograft dysfunction with an asymptomatic rise in serum creatinine, about 3 to 39 months posttransplant. Urinary decoy cells are positive in two patients (22.2%). The histologic changes of BKVN are not pathognomonic, and can be mistaken for allograft rejection, ie, tubulointerstitial nephritis with varying degrees of inflammatory infiltrates, tubulitis and tubular atrophy, and fibrosis. Typical findings on histology are focal interstitial mononuclear inflammatory cell infiltrates, presence of plasma cells, necrotic tubular epithelium, and presence of homogenous intranuclear inclusion bodies. Immunohistochemistry with SV40 staining were positive in allograft. Graft loss occurred in one patient and the other 8 showed progressive allograft dysfunction. Conclusion: The definitive diagnosis of BKV disease requires renal biopsy. Immunohistochemistry with SV40 staining has been used as an indirect method to document the presence of BKVAN.展开更多
To evaluate the role of glucose transporter- l (GLUT1) in the glucose uptake of glomerular mesangial cells. Methods. Cultured C57/SJL mouse mesangial cells were used in the study. The expression of GLUT1 mRNA was dete...To evaluate the role of glucose transporter- l (GLUT1) in the glucose uptake of glomerular mesangial cells. Methods. Cultured C57/SJL mouse mesangial cells were used in the study. The expression of GLUT1 mRNA was detected by RT- PCR. The expression of GLUT1 protein was detected by immunofluorescence and flow cytometry. The uptake of glucose and its kinetics were determined by 2- deoxy- [3H]- D- glucose uptake. Results. Both GLUT1 mRNA and protein were found in mouse glomerular mesangial cells. 2- deoxy- D- glucose uptake and kinetics assay showed that this glucose transporter had high affinity for glucose and the glucose uptake specificity was further confirmed by phloretin. Conclusion. Functional GLUT1 did present in mouse mesangial cells cultured in vitro and it might be the predominant transporter mediated the uptake of glucose into mesangial cells.展开更多
Iron is an indispensable trace element in mammals and performs several important physiological functions in the body.Dynamic equilibrium in iron metabolism exists.Iron uptake,storage,and output are in equilibrium as w...Iron is an indispensable trace element in mammals and performs several important physiological functions in the body.Dynamic equilibrium in iron metabolism exists.Iron uptake,storage,and output are in equilibrium as well.Several laboratory animal models have shown that iron deficiency and deposition can lead to a variety of functional disorders.Cardiac diseases caused by iron deposition in laboratory animal models are caused by abnormal oxidative stress,electrophysiological changes,iron metabolism-related gene defects,myocardial cell apoptosis,fibrosis,ferroptosis,and other causes.This review discusses the causes of heart disease related to iron deposition in laboratory animal models to illustrate further the impact of effective iron removal therapy on cardiac disease associated with iron deposition.In addition,this review demonstrates the possibility of elucidating the precise molecular mechanism of iron abnormality in heart diseases in experimental animal models and the feasibility of using iron abnormality as a target for developing new therapeutic drugs for the treatment of heart disease.展开更多
To investigate the effectiveness of using continuous veno venous hemofiltration (CVVH) in the treatment of acute necrotizing pancreatitis (ANP) Methods Thirteen ANP patients were involved in this study, including 4 fe...To investigate the effectiveness of using continuous veno venous hemofiltration (CVVH) in the treatment of acute necrotizing pancreatitis (ANP) Methods Thirteen ANP patients were involved in this study, including 4 females and 9 ma les, averaging 50 6±10 8 years old CT scans upon admission revealed 33% necrosis involving the body of the pancreas in 2 patients, 67% necrosis in 3 patients and 100% necrosis in the other 8; the CT severity score was 8 9±2 1 CVVH was maintained for at least 72 hours and the AN69 hemofilter (1 2 m 2) was changed every 24 hours The ultrafiltration rate during CVVH was 2993 9±983 0 m l/h, the blood flow rate was 250-300 ml/min, and the substitute fluid was infused in a pre-diluted manner Low molecular weight heparin was used as anticoagulant Results CVVH was well tolerated in all the patients Bloody abdominal cavity drainage fluid was observed in 2 patients, but no other side-effects related with CVVH were observed Two patients died of systemic fungal infections and another died o f intracranial fungi infection, resulting in an ICU mortality of 23 1% Ten of the patients survived in the ICU, but one of them died for other reasons unrelated to the SAP before discharge The APACHE Ⅱ score before CVVH was 15 2±6 5, but decreased significantly to 8 1±5 3, 7 5±4 9 and 8 0±5 2 at the 24th, 48th and 72nd hour after CVVH, respectively (P<0 01) Serum concentration of IL-1β and TNFα decreased to the trough at the 6th hour after a new hemofilter was used and increased slowly to pre-CVVH levels 12 hours later After CVVH had ceased, the serum levels of two cytokines i ncreased to their peaks at the 120th hour and decreased eventually at the 144th hour The sieving coefficient (SC) of IL-1β and TNFα was 0 33±0 11 and 0 16±0 08 Conclusion CVVH offered therapeutic options for ANP and was well tolerated resulting in clearance of IL-1β and TNFα; CVVH at early stages of SAP may contribute to the improvement of展开更多
Background:Type 2diabetes (T2DM)patients are susceptible to Helicobacterpylori (HP),and it has been reported that the occurrence of proteinuria is associated with HP infection in T2DM patients;however,this view remain...Background:Type 2diabetes (T2DM)patients are susceptible to Helicobacterpylori (HP),and it has been reported that the occurrence of proteinuria is associated with HP infection in T2DM patients;however,this view remains controversial.This meta-analysis aimed to explore the association between HP infection and the occurrence of proteinuria in T2DM patients.In addition,we hope to provide some recommendations to readers in clinical or related fields. Methods:Our meta-analysis was conducted with the methodology of the Cochrane Collaboration.Search strategies were formulated by relevant professionals.Case-control studies that compared the occurrence ofproteinuria in T2DM patients with and without HP infection were involved in our meta-analysis.Relevant English or Chinese studies were searched on online databases before 2018,including PubMed,the Cochrane library,Medline,Google Scholar,the China National Infrastructure,and Wanfang database.The search strategies were "diabetic proteinuria,diabetic microalbuminuria,diabetic albumainuria,diabetic kidney disease,diabetic renal dysfunction,diabetic renal disease,diabetic nephropathy,diabetic complications,and diabetic mellitus,combined with HP."The quality of these involved articles was separately assessed by two investigators using the Newcastle-Ottawa Scale (NOS).Odds ratios (ORs)and associated 95% confidence intervals (CIs)were extracted and pooled using fixed-effects models. Results:Seven studies involving 1029participants were included.The quality of these seven articles was all above five stars as assessed by NOS,and there was no significant publication bias in our meta-analysis.We found that T2DM patients with HP infection had a 2.00 times higher risk of the occurrence of proteinuria than patients without HP infection (OR:2.00,95%CI:1.48-2.69). Conclusions:Our analysis showed that HP infection was associated with the occurrence of proteinuria in T2DM patients.HP radical surgery might be a therapeutic option for protecting kidney function in patients with T2DM.展开更多
Background: Immunoglobulin A nephropathy (IgAN) is the most common pathological type of glomerular disease. Kidney biopsy, the gold standard for IgAN diagnosis, has not been routinely applied in hospitals worldwide du...Background: Immunoglobulin A nephropathy (IgAN) is the most common pathological type of glomerular disease. Kidney biopsy, the gold standard for IgAN diagnosis, has not been routinely applied in hospitals worldwide due to its invasion nature. Thus, we aim to establish a non-invasive diagnostic model and determine markers to evaluate disease severity by analyzing the serological parameters and pathological stages of patients with IgAN. Methods: A total of 272 biopsy-diagnosed IgAN inpatients and 518 non-IgA nephropathy inpatients from the Department of Nephrology of Chinese People's Liberation Army General Hospital were recruited for this study. Routine blood examination, blood coagulation testing, immunoglobulin-complement testing, and clinical biochemistry testing were conducted and pathological stages were analyzed according to Lee grading system. The serological parameters and pathological stages were analyzed. The receiver operating characteristic (ROC) analysis was performed to estimate the diagnostic value of the clinical factors. Logistic regression was used to establish the diagnostic model. Results: There were 15 significantly different serological parameters between the IgAN and non-IgAN groups (all P< 0.05). The ROC analysis was performed to measure the diagnostic value for IgAN of these parameters and the results showed that the area under the ROC curve (AUC) of total protein (TP), total cholesterol (TC), fibrinogen (FIB), D-dimer (D2), immunoglobulin A (IgA), and immunoglobulin G (IgG) were more than 0.70. The AUC of the "TC + FIB + D2 + IgA + age" combination was 0.86, with a sensitivity of 85.98% and a specificity of 73.85%. Pathological grades of Ⅰ,Ⅱ,Ⅲ,Ⅳ, and Ⅴ accounted for 2.21 %, 17.65%, 62.50%, 11.76%, and 5.88%, respectively, with grade Ⅲ being the most prevalent. The levels of urea nitrogen (UN)(13.57土 5.95 vs. 6.06 土 3.63, 5.92 + 2.97, 5.41 ± 1.73, and 8.41 ±3.72μmol/L, respectively) and creatinine (Cr)(292.19± 162.21 vs. 80.42±24.75, 103.79±72.72, 96.41 ±33.79, and 163.04±47.51 μmol/L, respectively) were significantly higher in grade V than in the other grades, and the levels of TP (64.45±7.56, 67.16±6.94, 63.22±8.56, and 61.41 ± 10.86 vs. 37.47 ± 5.6 mg/d, respectively), direct bilirubin (DB)(2.34± 1.23, 2.58± 1.40, 1.91 ±0.97, and 1.81±1.44 vs. 0.74±0.57μmol/L, respectively), and IgA (310.35± 103.78, 318.48± 107.54, 292.58±81.85, and 323.29± 181.67 vs. 227.17±68.12g/L, respectively) were significantly increased in grades II-V compared with grade I (all P<0.05). Conclusions: The established diagnostic model that combined multiple factors (TC, FIB, D2, IgA, and age) might be used for IgAN non-invasive diagnosis. TP, DB, IgA, Cr, and UN have the potential to be used to evaluate IgAN disease severity.展开更多
Background: Accurate estimation of the glomerular filtration rate (GFR) and staging of chronic kidney disease (CKD) are important. Currently, there is no research on the differences in several estimated GFR equations ...Background: Accurate estimation of the glomerular filtration rate (GFR) and staging of chronic kidney disease (CKD) are important. Currently, there is no research on the differences in several estimated GFR equations for staging CKD in a large sample of centenarians. Thus, this study aimed to investigate the differences in CKD staging with the most commonly used equations and to analyze sources of discrepancy. Methods: A total of 966 centenarians were enrolled in this study from June 2014 to December 2016 in Hainan province, China. The GFR with the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study 1 (BIS1) equations were estimated. Agreement between these equations was investigated with the k statistic and Bland-Altman plots. Sources of discrepancy were investigated by partial correlation analysis. Results: The k values of the MDRD and CKD-EPI equations, MDRD and BIS1 equations, and CKD-EPI and BIS1 equations were 0.610, 0.253, and 0.381, respectively. Serum creatinine (Scr) explained 10.96%, 41.60% and 17.06% of the variability in these three comparisons, respectively. Serum uric acid (SUA) explained 3.65% and 5.43% of the variability in the first 2 comparisons, respectively. Gender was associated with significant differences in these 3 comparisons (P<0.001). Conclusions: The strengths of agreement between the MDRD and CKD-EPI equations were substantial, but those between the MDRD and BIS 1 equations and the CKD-EPI and BIS 1 equations were fair. The difference in CKD staging of the first 2 comparisons strongly depended on Scr, SUA and gender, and that of CKD-EPI and BIS1 equations strongly depended on Scr and gender. The incidence at various stages of CKD staging was quite different. Thus, a new equation that is more suitable for the elderly needs to be built in the future.展开更多
Mitochondrial injury and endoplasmic reticulum(ER)stress are considered to be the key mechanisms of renal ischemia-reperfusion(I/R)injury.Mitochondria are membrane-bound organelles that form close physical contact wit...Mitochondrial injury and endoplasmic reticulum(ER)stress are considered to be the key mechanisms of renal ischemia-reperfusion(I/R)injury.Mitochondria are membrane-bound organelles that form close physical contact with a specific domain of the ER,known as mitochondrial-associated membranes.The close physical contact between them is mainly restrained by ER-mitochondria tethering complexes,which can play an important role in mitochondrial damage,ER stress,lipid homeostasis,and cell death.Several ER-mitochondria tethering complex components are involved in the process of renal I/R injury.A better understanding of the physical and functional interaction between ER and mitochondria is helpful to further clarify the mechanism of renal I/R injury and provide potential therapeutic targets.In this review,we aim to describe the structure of the tethering complex and elucidate its pivotal role in renal I/R injury by summarizing its role in many important mechanisms,such as mitophagy,mitochondrial fission,mitochondrial fusion,apoptosis and necrosis,ER stress,mitochondrial substance transport,and lipid metabolism.展开更多
To the Editor:Diabetic kidney disease (DKD)is the most common cause of end-stage renal disease (ESRD);however,the onset of DKD is difficult to detect.[1]When persistent microalbuminuria becomes detectable,DKD has alre...To the Editor:Diabetic kidney disease (DKD)is the most common cause of end-stage renal disease (ESRD);however,the onset of DKD is difficult to detect.[1]When persistent microalbuminuria becomes detectable,DKD has already progressed to the third disease stage,and finding biomarkers that are more sensitive than microalbuminuria is therefore necessary to indicate kidney damage at an earlier stage of DKD.[2]Both glomerular and tubulointerstitial damages have been repeatedly demonstrated to be important factors in the pathophysiology of DKD.[3] Therefore,we investigated the expression levels of six markers closely related to the glomerulus and renal tubule.展开更多
To the Editor:Diabetic nephropathy (DN)is the leading cause of chronic renal diseases and accounts for almost 50% of all end-stage renal diseases worldwide.The prevalence of DN increased significantly after 2010in Chi...To the Editor:Diabetic nephropathy (DN)is the leading cause of chronic renal diseases and accounts for almost 50% of all end-stage renal diseases worldwide.The prevalence of DN increased significantly after 2010in China.[1,2] DN is clinically characterized by proteinuria and morphological and ultrastructural changes in the kidney.The pathogenesis of DN is multifactorial and extremely complex,including hyperglycemia,transforming growth factor (TGF)-β1,angiotensin Ⅱ,DNA methylation,chromatin histone modification,microRNAs,and long noncoding RNAs.展开更多
Objectives To evaluate the safety and define the contraindication of regional citrate anticoagulation treatment on various critically ill patients being treated by continuous blood purification, who also had bleeding ...Objectives To evaluate the safety and define the contraindication of regional citrate anticoagulation treatment on various critically ill patients being treated by continuous blood purification, who also had bleeding tendencies. Methods Forty critically ill patients being treated by continuous blood purification (CBP) were involved in this study. Due to their bleeding tendencies, regional citrate anticoagulation treatment was given to all of them. Those with hepatic function impairment (n=10) were classified as Group A, those with hypoxemia were classified as Group B (n=10), and the others as Group C (n=20). Blood samples were collected before treatment, and at 4, 12, 24, 36, and 48 hour intervals during CBP. These samples then were used arterial blood gas analysis, whole blood activated clotting time (WBACT) pre- and post-filter, and serum ionized calcium examination. Results WBACT pre-filter showed little fluctuant through the 48hr period of CBP, and WBACT post-filter showed obvious prolongation than that of the pre-filter ( P <0.05) at all time points. Metabolic acidosis was found in Group A patients before CBP, and improved during CBP. Normal acid-base conditions of patients were disturbed and deteriorated in Group B during CBP, but not in Group C. Serum ionized calcium was maintained at a normal range during CBP in Group A and C patients, but declined significantly in Group B patients (vs. pre-treatment, P <0.05). Conclusions Regional citrate anticoagulation can be safely used in conjunction with CBP treatment for patients with hepatic function impairment , but may induce acidosis and a decline in serum ionized calcium when used with hypoxemic patients.展开更多
Objectives To investigate the effect of rhein on endothelial plasminogen activator inhibitor-1 (PAI-1) mRNA expression and protein production induced by transforming growth factor β1 (TGFβ1), and to explore the mech...Objectives To investigate the effect of rhein on endothelial plasminogen activator inhibitor-1 (PAI-1) mRNA expression and protein production induced by transforming growth factor β1 (TGFβ1), and to explore the mechanism of the protective action of rhein on endothelial cells. Methods A human umbilical endothelium derived cell line (ECV-304) from ATCC was used in this study. The PAI-1 mRNA expression and protein synthesis in the endothelial cells were detected by Northern blot and flow cytometry analysis, respectively. The activity of phospho-p44/p42 MAP kinase induced by TGFβ1 was determined by immunoprecipitation analysis and western blot. Results TGFβ1 rapidly increased PAI-1 mRNA expression in the endothelial cells, and this effect lasted at least 24 hours. The upregulation of PAI-1 mRNA expression induced by TGFβ1 in endothelial cells was inhibited by rhein in a dose-dependent manner. In addition, rhein inhibited endothelial PAI-1 protein production. Further study revealed that rhein had a significant inhibitory effect on the activity of phospho-p44/p42 MAP kinase induced by TGFβ1 in human endothelial cells. Conclusions Our results showed that rhein may have a protective effect on the endothelial dysfunction by inhibiting overexpression of PAI-1, indicating a way for the treatment of vascular diseases.展开更多
Background:Treatment with the dipeptidyl peptidase-4 inhibitors (DPP4i)and angiotensin receptor blockers (ARBs)in patients with type 2 diabetic nephropathy (DN)has not been well characterized.This study aimed to asses...Background:Treatment with the dipeptidyl peptidase-4 inhibitors (DPP4i)and angiotensin receptor blockers (ARBs)in patients with type 2 diabetic nephropathy (DN)has not been well characterized.This study aimed to assess the renoprotection of this combined treatment in DN patients. Methods:A total of 159 type 2 DN patients from 2013to 2015were enrolled retrospectively from a prospective DN cohort at the National Clinical Research Center of Kidney Diseases,Jinling Hospital (China).Fifty-seven patients received DPP4i and ARB treatment,and 102 patients were treated with ARBs alone.All patients were followed up for at least 12 months.Statistical analyses were performed using Stata version 12.0. Results:There were no significant differences at baseline for age,sex,body mass index,duration of diabetes,fasting blood glucose (FBG), hemoglobin Ale (HbAlc),and estimated glomerular filtration rate (eGFR)between the two groups.Antihypertensive and antidiabetie medication use was similar in each group except calcium channel antagonists (P =0.032).No significant changes in FBG and HbAlc were observed in the two groups after treatment.The eGFR decreased slower in the DPP4i +ARB group than in the ARB group at 12 months (△12months:-2.48±13.86vs.-6.81±12.52ml·min^-1·1.73m^-2,P =0.044).In addition,proteinuria was decreased further in the DPP4i +ARB group than in the ARB group after 24months of treatment (△24months:-0.18[-1.00,0.17]vs.0.32[-0.35,0.88], P =0.031).There were 36 patients with an eGFR decrease of more than 30% over 24 months.After adjusting for FB G,HbA1c,and other risk factors,DPP4i +ARB treatment was still associated with a reduced incidence of an eGFR decrease of 20% or 30%. Conclusions:The combined treatment of DPP4i andARBs is superior to ARBs alone,as evidenced by the greater proteinuria reduction and lower eGFR decline.In addition,the renoprotection of DPP4i combined with ARBs was independent ofglycemic control.展开更多
Background Lipoprotein glomerulopathy (LPG), once recognized as a rare glomerular disease, has been reported around the world in recent years. In this study, we reported 8 patients of LPG and aimed to explore the clin...Background Lipoprotein glomerulopathy (LPG), once recognized as a rare glomerular disease, has been reported around the world in recent years. In this study, we reported 8 patients of LPG and aimed to explore the clinical features and pathological characteristics of LPG under light microscope, immunofluorescence staining, and electron microscope.Methods Clinical manifestations were recorded on the day of renal biopsy. Biochemical patterns of lipids and lipoproteins were detected by routine examination. Plasma concentrations of apo B and apo E were determined by radial immunodiffusion assays. Biopsy specimens were then processed for light microscopy, immunohistochemical staining for immunoglobulins and complement components, and electron microscopy. Glomerular deposition of apo A, B, and E were detected using monoclonal antibodies on cryostatic sections.Results All of the eight patients presented with edema, microscopic hematuria, severe proteinuria, anemia, and enlarged kidney size. Biochemical profiles revealed high levels of triglycerides, apo B, and apo E. We noted increments of glomerular size and lipoprotein thrombi occupying capillary lumina in the glomeruli of all patients. Immunofluorescence staining showed that the thrombi were strongly positive for apo A, B, and E. Granules and various sizes of vacuoles were observed in the thrombi under electron microscope.Conclusion Compared with previous reports on LPG in other countries, unique clinical and pathological features were found in this group of Chinese LPG patients.展开更多
基金supported by grants from the National Natural Science Foundation of China[grant numbers 82003454,81903314,and 81872626]National Natural Science Foundation of Henan Province[grant number 222300420337]+3 种基金Chinese Nutrition Society-Bright Moon Seaweed Group Nutrition and Health Research Fund[grant number CNS-BMSG2020A63]Chinese Nutrition Society Zhendong National Physical Fitness and Health Research Fund[grant number CNS-ZD2019066]key R&D and promotion projects in Henan Province[grant numbers 212102310219,212102310110,and 202102310120]National Natural Science Foundation of China[grant number 81903314].
文摘Hypertension(HTN)and type 2 diabetes mellitus(T2DM)are interconnected metabolic diseases[1,2]that considerably increase susceptibility to microvascular and macrovascular disorders.In many patients,HTN and diabetes comorbidity(HDC)is caused by mutual pathogenic pathways,such as endothelial dysfunction,atherosclerosis,oxidative stress,and vascular inflammation[1].Hence.
基金supports from the Second Xiangya Hospital of Central South University,and the supports from Fund from Hunan Province health science and technology support
文摘Objective:To investigate the efficiency ofβ-galactosidase gene transfer into rat kidney with ultrasound-mediated microbubble destruction via different injection routes.Methods:A total of 25 Wistar rats were randomly divided into 5 groups.Four groups received a mixture of optison microbubbles(0.2 mL) and lacz plasmids(25μg) injection via renal artery,tail vein,anterior tibial muscle and renal parenchyma,respectively.The control group received a mixture of PBS (xx mL) and lacz plasmids(25μg) via renal artery.Three days after the gene transfer,ultrasound with fixed frequency and power(1 MHz,xxW) was delivered to the kidneys for 3 min.The efficiency of the gene transfer and expression was evaluated on the basis ofβ-galactosidase expression.The side effects of this method were evaluated by immunohistological method. Results:β-galactosidase expression could be observed only in tubules but not in glomeruli and interstitial area.The efficiency of renal artery group was higher than that of tail vein,anterior tibial muscle and renal parenchyma group(P【0.05).Immunohistochemical analysis revealed co-expression ofβ-galactosidase with a roximal tubule marker,megalin,which suggested that ultrasound enhanced gene transfer into the proximal tubular epithelial cells.Noβ-galactosidase expression was observed in the extrarenal organs.There were no evident pathological and biochemical changes after gene transfer.Conclusions:Ultrasound-mediated microbubble destruction can transfer gene into kidney via renal artery,tail vein,anterior tibial muscle and renal parenchyma.Compared with renal artery,administrating microbubbles via tail vein and anterior tibial muscle are more convenient and less vulnerarious.
文摘Objective: We prospectively investigated 121 renal allograft biopsy specimens performed in our center. Methods: BKVAN was diagnosed by light microscopic examination and a positive immunohistochemistry staining of anti-SV40 large T antibody in a biopsy specimen. Results: Of the 121 patients, nine were diagnosed with BKVAN (7.4%). Nine patients whith BKVN classically presents as allograft dysfunction with an asymptomatic rise in serum creatinine, about 3 to 39 months posttransplant. Urinary decoy cells are positive in two patients (22.2%). The histologic changes of BKVN are not pathognomonic, and can be mistaken for allograft rejection, ie, tubulointerstitial nephritis with varying degrees of inflammatory infiltrates, tubulitis and tubular atrophy, and fibrosis. Typical findings on histology are focal interstitial mononuclear inflammatory cell infiltrates, presence of plasma cells, necrotic tubular epithelium, and presence of homogenous intranuclear inclusion bodies. Immunohistochemistry with SV40 staining were positive in allograft. Graft loss occurred in one patient and the other 8 showed progressive allograft dysfunction. Conclusion: The definitive diagnosis of BKV disease requires renal biopsy. Immunohistochemistry with SV40 staining has been used as an indirect method to document the presence of BKVAN.
基金This work was supported by the National Natural Science Foundation of China (No.39870288)
文摘To evaluate the role of glucose transporter- l (GLUT1) in the glucose uptake of glomerular mesangial cells. Methods. Cultured C57/SJL mouse mesangial cells were used in the study. The expression of GLUT1 mRNA was detected by RT- PCR. The expression of GLUT1 protein was detected by immunofluorescence and flow cytometry. The uptake of glucose and its kinetics were determined by 2- deoxy- [3H]- D- glucose uptake. Results. Both GLUT1 mRNA and protein were found in mouse glomerular mesangial cells. 2- deoxy- D- glucose uptake and kinetics assay showed that this glucose transporter had high affinity for glucose and the glucose uptake specificity was further confirmed by phloretin. Conclusion. Functional GLUT1 did present in mouse mesangial cells cultured in vitro and it might be the predominant transporter mediated the uptake of glucose into mesangial cells.
基金supported by the National Natural Science Foundation of China(No.31900502&81903448)the Henan Medical Science and Technology Joint Building Program(No.LHGJ20190229&LHGJ20190265)+1 种基金the Natural Science Foundation of Henan Province(212300410275)the Key R&D and promotion Special Projects of Henan Province(No.212102310194).
文摘Iron is an indispensable trace element in mammals and performs several important physiological functions in the body.Dynamic equilibrium in iron metabolism exists.Iron uptake,storage,and output are in equilibrium as well.Several laboratory animal models have shown that iron deficiency and deposition can lead to a variety of functional disorders.Cardiac diseases caused by iron deposition in laboratory animal models are caused by abnormal oxidative stress,electrophysiological changes,iron metabolism-related gene defects,myocardial cell apoptosis,fibrosis,ferroptosis,and other causes.This review discusses the causes of heart disease related to iron deposition in laboratory animal models to illustrate further the impact of effective iron removal therapy on cardiac disease associated with iron deposition.In addition,this review demonstrates the possibility of elucidating the precise molecular mechanism of iron abnormality in heart diseases in experimental animal models and the feasibility of using iron abnormality as a target for developing new therapeutic drugs for the treatment of heart disease.
文摘To investigate the effectiveness of using continuous veno venous hemofiltration (CVVH) in the treatment of acute necrotizing pancreatitis (ANP) Methods Thirteen ANP patients were involved in this study, including 4 females and 9 ma les, averaging 50 6±10 8 years old CT scans upon admission revealed 33% necrosis involving the body of the pancreas in 2 patients, 67% necrosis in 3 patients and 100% necrosis in the other 8; the CT severity score was 8 9±2 1 CVVH was maintained for at least 72 hours and the AN69 hemofilter (1 2 m 2) was changed every 24 hours The ultrafiltration rate during CVVH was 2993 9±983 0 m l/h, the blood flow rate was 250-300 ml/min, and the substitute fluid was infused in a pre-diluted manner Low molecular weight heparin was used as anticoagulant Results CVVH was well tolerated in all the patients Bloody abdominal cavity drainage fluid was observed in 2 patients, but no other side-effects related with CVVH were observed Two patients died of systemic fungal infections and another died o f intracranial fungi infection, resulting in an ICU mortality of 23 1% Ten of the patients survived in the ICU, but one of them died for other reasons unrelated to the SAP before discharge The APACHE Ⅱ score before CVVH was 15 2±6 5, but decreased significantly to 8 1±5 3, 7 5±4 9 and 8 0±5 2 at the 24th, 48th and 72nd hour after CVVH, respectively (P<0 01) Serum concentration of IL-1β and TNFα decreased to the trough at the 6th hour after a new hemofilter was used and increased slowly to pre-CVVH levels 12 hours later After CVVH had ceased, the serum levels of two cytokines i ncreased to their peaks at the 120th hour and decreased eventually at the 144th hour The sieving coefficient (SC) of IL-1β and TNFα was 0 33±0 11 and 0 16±0 08 Conclusion CVVH offered therapeutic options for ANP and was well tolerated resulting in clearance of IL-1β and TNFα; CVVH at early stages of SAP may contribute to the improvement of
基金grants from National Key R&D Program of China (No.2016YFC 1305500)National Natural Science Foundation of China (Nos.61471399,61671479, U 1604284,and 81670663)+1 种基金 National Key Research and Development Program (No.2016YFC 1305404)Special Research Project on Health Care of the Chinese People's Liberation Army (No.15BJZ35).
文摘Background:Type 2diabetes (T2DM)patients are susceptible to Helicobacterpylori (HP),and it has been reported that the occurrence of proteinuria is associated with HP infection in T2DM patients;however,this view remains controversial.This meta-analysis aimed to explore the association between HP infection and the occurrence of proteinuria in T2DM patients.In addition,we hope to provide some recommendations to readers in clinical or related fields. Methods:Our meta-analysis was conducted with the methodology of the Cochrane Collaboration.Search strategies were formulated by relevant professionals.Case-control studies that compared the occurrence ofproteinuria in T2DM patients with and without HP infection were involved in our meta-analysis.Relevant English or Chinese studies were searched on online databases before 2018,including PubMed,the Cochrane library,Medline,Google Scholar,the China National Infrastructure,and Wanfang database.The search strategies were "diabetic proteinuria,diabetic microalbuminuria,diabetic albumainuria,diabetic kidney disease,diabetic renal dysfunction,diabetic renal disease,diabetic nephropathy,diabetic complications,and diabetic mellitus,combined with HP."The quality of these involved articles was separately assessed by two investigators using the Newcastle-Ottawa Scale (NOS).Odds ratios (ORs)and associated 95% confidence intervals (CIs)were extracted and pooled using fixed-effects models. Results:Seven studies involving 1029participants were included.The quality of these seven articles was all above five stars as assessed by NOS,and there was no significant publication bias in our meta-analysis.We found that T2DM patients with HP infection had a 2.00 times higher risk of the occurrence of proteinuria than patients without HP infection (OR:2.00,95%CI:1.48-2.69). Conclusions:Our analysis showed that HP infection was associated with the occurrence of proteinuria in T2DM patients.HP radical surgery might be a therapeutic option for protecting kidney function in patients with T2DM.
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 30830056 and No. U0932002）. Conflict of interests： None.
基金grants from the National Key R&D Program of China (No. 2016YFC1305500)the National Natural Science Foundation of China (Nos. 61471399, 61671479, and 81670663)+1 种基金the National Key Research and Development Program (No. 2016YFC1305404)and the Joint Funds of National Natural Science Foundation of China and Henan Province (No. U1604284).
文摘Background: Immunoglobulin A nephropathy (IgAN) is the most common pathological type of glomerular disease. Kidney biopsy, the gold standard for IgAN diagnosis, has not been routinely applied in hospitals worldwide due to its invasion nature. Thus, we aim to establish a non-invasive diagnostic model and determine markers to evaluate disease severity by analyzing the serological parameters and pathological stages of patients with IgAN. Methods: A total of 272 biopsy-diagnosed IgAN inpatients and 518 non-IgA nephropathy inpatients from the Department of Nephrology of Chinese People's Liberation Army General Hospital were recruited for this study. Routine blood examination, blood coagulation testing, immunoglobulin-complement testing, and clinical biochemistry testing were conducted and pathological stages were analyzed according to Lee grading system. The serological parameters and pathological stages were analyzed. The receiver operating characteristic (ROC) analysis was performed to estimate the diagnostic value of the clinical factors. Logistic regression was used to establish the diagnostic model. Results: There were 15 significantly different serological parameters between the IgAN and non-IgAN groups (all P< 0.05). The ROC analysis was performed to measure the diagnostic value for IgAN of these parameters and the results showed that the area under the ROC curve (AUC) of total protein (TP), total cholesterol (TC), fibrinogen (FIB), D-dimer (D2), immunoglobulin A (IgA), and immunoglobulin G (IgG) were more than 0.70. The AUC of the "TC + FIB + D2 + IgA + age" combination was 0.86, with a sensitivity of 85.98% and a specificity of 73.85%. Pathological grades of Ⅰ,Ⅱ,Ⅲ,Ⅳ, and Ⅴ accounted for 2.21 %, 17.65%, 62.50%, 11.76%, and 5.88%, respectively, with grade Ⅲ being the most prevalent. The levels of urea nitrogen (UN)(13.57土 5.95 vs. 6.06 土 3.63, 5.92 + 2.97, 5.41 ± 1.73, and 8.41 ±3.72μmol/L, respectively) and creatinine (Cr)(292.19± 162.21 vs. 80.42±24.75, 103.79±72.72, 96.41 ±33.79, and 163.04±47.51 μmol/L, respectively) were significantly higher in grade V than in the other grades, and the levels of TP (64.45±7.56, 67.16±6.94, 63.22±8.56, and 61.41 ± 10.86 vs. 37.47 ± 5.6 mg/d, respectively), direct bilirubin (DB)(2.34± 1.23, 2.58± 1.40, 1.91 ±0.97, and 1.81±1.44 vs. 0.74±0.57μmol/L, respectively), and IgA (310.35± 103.78, 318.48± 107.54, 292.58±81.85, and 323.29± 181.67 vs. 227.17±68.12g/L, respectively) were significantly increased in grades II-V compared with grade I (all P<0.05). Conclusions: The established diagnostic model that combined multiple factors (TC, FIB, D2, IgA, and age) might be used for IgAN non-invasive diagnosis. TP, DB, IgA, Cr, and UN have the potential to be used to evaluate IgAN disease severity.
基金National Key R&D Program of China (No.2016YFC1305500)Key Research and Development Program of Hainan (Nos.ZDYF2016135 and ZDYF2017095)+2 种基金the National Natural Science Foundation of China (Nos.61471399,61671479,and 81670663)the National Key Research and Development Program (No. 2016YFC1305404)the Joint Funds of National Natural Science Foundation of China and Henan province (No.U1604284).
文摘Background: Accurate estimation of the glomerular filtration rate (GFR) and staging of chronic kidney disease (CKD) are important. Currently, there is no research on the differences in several estimated GFR equations for staging CKD in a large sample of centenarians. Thus, this study aimed to investigate the differences in CKD staging with the most commonly used equations and to analyze sources of discrepancy. Methods: A total of 966 centenarians were enrolled in this study from June 2014 to December 2016 in Hainan province, China. The GFR with the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study 1 (BIS1) equations were estimated. Agreement between these equations was investigated with the k statistic and Bland-Altman plots. Sources of discrepancy were investigated by partial correlation analysis. Results: The k values of the MDRD and CKD-EPI equations, MDRD and BIS1 equations, and CKD-EPI and BIS1 equations were 0.610, 0.253, and 0.381, respectively. Serum creatinine (Scr) explained 10.96%, 41.60% and 17.06% of the variability in these three comparisons, respectively. Serum uric acid (SUA) explained 3.65% and 5.43% of the variability in the first 2 comparisons, respectively. Gender was associated with significant differences in these 3 comparisons (P<0.001). Conclusions: The strengths of agreement between the MDRD and CKD-EPI equations were substantial, but those between the MDRD and BIS 1 equations and the CKD-EPI and BIS 1 equations were fair. The difference in CKD staging of the first 2 comparisons strongly depended on Scr, SUA and gender, and that of CKD-EPI and BIS1 equations strongly depended on Scr and gender. The incidence at various stages of CKD staging was quite different. Thus, a new equation that is more suitable for the elderly needs to be built in the future.
基金grants from the National Natural Science Foundation of China(Nos.61971441,61671479,and 81804056)the National Key R&D Program of China(No.2016YFC1305500)。
文摘Mitochondrial injury and endoplasmic reticulum(ER)stress are considered to be the key mechanisms of renal ischemia-reperfusion(I/R)injury.Mitochondria are membrane-bound organelles that form close physical contact with a specific domain of the ER,known as mitochondrial-associated membranes.The close physical contact between them is mainly restrained by ER-mitochondria tethering complexes,which can play an important role in mitochondrial damage,ER stress,lipid homeostasis,and cell death.Several ER-mitochondria tethering complex components are involved in the process of renal I/R injury.A better understanding of the physical and functional interaction between ER and mitochondria is helpful to further clarify the mechanism of renal I/R injury and provide potential therapeutic targets.In this review,we aim to describe the structure of the tethering complex and elucidate its pivotal role in renal I/R injury by summarizing its role in many important mechanisms,such as mitophagy,mitochondrial fission,mitochondrial fusion,apoptosis and necrosis,ER stress,mitochondrial substance transport,and lipid metabolism.
基金the grants from the National Key R&D Program of China (No.2016YFC1305500and No.2016YFC 1305404)the National Natural Science Foundation of China (No.61471399,No.61671479,and No.81670663)+1 种基金the Joint Funds of National Natural Science Foundation of China and Henan Province (No.U1604284) the Special Research Project on Health Care of the Chinese People's Liberation Army (No.15BJZ35).
文摘To the Editor:Diabetic kidney disease (DKD)is the most common cause of end-stage renal disease (ESRD);however,the onset of DKD is difficult to detect.[1]When persistent microalbuminuria becomes detectable,DKD has already progressed to the third disease stage,and finding biomarkers that are more sensitive than microalbuminuria is therefore necessary to indicate kidney damage at an earlier stage of DKD.[2]Both glomerular and tubulointerstitial damages have been repeatedly demonstrated to be important factors in the pathophysiology of DKD.[3] Therefore,we investigated the expression levels of six markers closely related to the glomerulus and renal tubule.
文摘To the Editor:Diabetic nephropathy (DN)is the leading cause of chronic renal diseases and accounts for almost 50% of all end-stage renal diseases worldwide.The prevalence of DN increased significantly after 2010in China.[1,2] DN is clinically characterized by proteinuria and morphological and ultrastructural changes in the kidney.The pathogenesis of DN is multifactorial and extremely complex,including hyperglycemia,transforming growth factor (TGF)-β1,angiotensin Ⅱ,DNA methylation,chromatin histone modification,microRNAs,and long noncoding RNAs.
基金ThisstudywassupportedbyPLATenth Five YearStudyPlan(No 0 1L0 0 7)
文摘Objectives To evaluate the safety and define the contraindication of regional citrate anticoagulation treatment on various critically ill patients being treated by continuous blood purification, who also had bleeding tendencies. Methods Forty critically ill patients being treated by continuous blood purification (CBP) were involved in this study. Due to their bleeding tendencies, regional citrate anticoagulation treatment was given to all of them. Those with hepatic function impairment (n=10) were classified as Group A, those with hypoxemia were classified as Group B (n=10), and the others as Group C (n=20). Blood samples were collected before treatment, and at 4, 12, 24, 36, and 48 hour intervals during CBP. These samples then were used arterial blood gas analysis, whole blood activated clotting time (WBACT) pre- and post-filter, and serum ionized calcium examination. Results WBACT pre-filter showed little fluctuant through the 48hr period of CBP, and WBACT post-filter showed obvious prolongation than that of the pre-filter ( P <0.05) at all time points. Metabolic acidosis was found in Group A patients before CBP, and improved during CBP. Normal acid-base conditions of patients were disturbed and deteriorated in Group B during CBP, but not in Group C. Serum ionized calcium was maintained at a normal range during CBP in Group A and C patients, but declined significantly in Group B patients (vs. pre-treatment, P <0.05). Conclusions Regional citrate anticoagulation can be safely used in conjunction with CBP treatment for patients with hepatic function impairment , but may induce acidosis and a decline in serum ionized calcium when used with hypoxemic patients.
基金ThisstudywaspartlysupportedbyagrantfromtheNationalNaturalScienceFoundationofChina (No 3 0 171191)
文摘Objectives To investigate the effect of rhein on endothelial plasminogen activator inhibitor-1 (PAI-1) mRNA expression and protein production induced by transforming growth factor β1 (TGFβ1), and to explore the mechanism of the protective action of rhein on endothelial cells. Methods A human umbilical endothelium derived cell line (ECV-304) from ATCC was used in this study. The PAI-1 mRNA expression and protein synthesis in the endothelial cells were detected by Northern blot and flow cytometry analysis, respectively. The activity of phospho-p44/p42 MAP kinase induced by TGFβ1 was determined by immunoprecipitation analysis and western blot. Results TGFβ1 rapidly increased PAI-1 mRNA expression in the endothelial cells, and this effect lasted at least 24 hours. The upregulation of PAI-1 mRNA expression induced by TGFβ1 in endothelial cells was inhibited by rhein in a dose-dependent manner. In addition, rhein inhibited endothelial PAI-1 protein production. Further study revealed that rhein had a significant inhibitory effect on the activity of phospho-p44/p42 MAP kinase induced by TGFβ1 in human endothelial cells. Conclusions Our results showed that rhein may have a protective effect on the endothelial dysfunction by inhibiting overexpression of PAI-1, indicating a way for the treatment of vascular diseases.
基金grants from the Key Research and Development Program of Jiangsu Province (No.BE2016747) National Natural Science Foundation of China (No.81500548and No.81500556).
文摘Background:Treatment with the dipeptidyl peptidase-4 inhibitors (DPP4i)and angiotensin receptor blockers (ARBs)in patients with type 2 diabetic nephropathy (DN)has not been well characterized.This study aimed to assess the renoprotection of this combined treatment in DN patients. Methods:A total of 159 type 2 DN patients from 2013to 2015were enrolled retrospectively from a prospective DN cohort at the National Clinical Research Center of Kidney Diseases,Jinling Hospital (China).Fifty-seven patients received DPP4i and ARB treatment,and 102 patients were treated with ARBs alone.All patients were followed up for at least 12 months.Statistical analyses were performed using Stata version 12.0. Results:There were no significant differences at baseline for age,sex,body mass index,duration of diabetes,fasting blood glucose (FBG), hemoglobin Ale (HbAlc),and estimated glomerular filtration rate (eGFR)between the two groups.Antihypertensive and antidiabetie medication use was similar in each group except calcium channel antagonists (P =0.032).No significant changes in FBG and HbAlc were observed in the two groups after treatment.The eGFR decreased slower in the DPP4i +ARB group than in the ARB group at 12 months (△12months:-2.48±13.86vs.-6.81±12.52ml·min^-1·1.73m^-2,P =0.044).In addition,proteinuria was decreased further in the DPP4i +ARB group than in the ARB group after 24months of treatment (△24months:-0.18[-1.00,0.17]vs.0.32[-0.35,0.88], P =0.031).There were 36 patients with an eGFR decrease of more than 30% over 24 months.After adjusting for FB G,HbA1c,and other risk factors,DPP4i +ARB treatment was still associated with a reduced incidence of an eGFR decrease of 20% or 30%. Conclusions:The combined treatment of DPP4i andARBs is superior to ARBs alone,as evidenced by the greater proteinuria reduction and lower eGFR decline.In addition,the renoprotection of DPP4i combined with ARBs was independent ofglycemic control.
文摘Background Lipoprotein glomerulopathy (LPG), once recognized as a rare glomerular disease, has been reported around the world in recent years. In this study, we reported 8 patients of LPG and aimed to explore the clinical features and pathological characteristics of LPG under light microscope, immunofluorescence staining, and electron microscope.Methods Clinical manifestations were recorded on the day of renal biopsy. Biochemical patterns of lipids and lipoproteins were detected by routine examination. Plasma concentrations of apo B and apo E were determined by radial immunodiffusion assays. Biopsy specimens were then processed for light microscopy, immunohistochemical staining for immunoglobulins and complement components, and electron microscopy. Glomerular deposition of apo A, B, and E were detected using monoclonal antibodies on cryostatic sections.Results All of the eight patients presented with edema, microscopic hematuria, severe proteinuria, anemia, and enlarged kidney size. Biochemical profiles revealed high levels of triglycerides, apo B, and apo E. We noted increments of glomerular size and lipoprotein thrombi occupying capillary lumina in the glomeruli of all patients. Immunofluorescence staining showed that the thrombi were strongly positive for apo A, B, and E. Granules and various sizes of vacuoles were observed in the thrombi under electron microscope.Conclusion Compared with previous reports on LPG in other countries, unique clinical and pathological features were found in this group of Chinese LPG patients.
