Development and validation of a prognostic model for survival in peritoneal dialysis patients / 中华肾脏病杂志

Objective:To develop and validate a nomogram for predicting the 1-and 3-year survival rates of patients receiving peritoneal dialysis.Methods:Patients who underwent peritoneal dialysis for the first time in Zhujiang hospital from January 1, 2010 to December 31, 2017 were enrolled. The patients from January 1, 2014 to December 31, 2017 were enrolled in a training dataset. Baseline clinical data were collected and the primary endpoint was all-cause death. Cox proportional hazard regression models were used to analyze risk factors affecting the survival rates. Nomograms were generated using the R rms package. The Harrell' concordance index (C-index), receiver operating characteristic curve and calibration curve were used to verify the performance of the model. Patients who underwent peritoneal dialysis from January 1, 2010 to December 31, 2013 were then selected to validate the external predictive accuracy of the prediction models.Results:The prediction cohort enrolled 457 patients, with a median follow-up time of 27.67(18.37, 39.22) months, and 64 patients (14.00%) died during follow-up. The 1-and 3-year cumulative survival rates were 96.4% and 83.0%. Multivariate analysis showed that aging (every 1 year old increase, HR=1.07, 95% CI 1.04-1.09, P<0.001), stroke ( HR=3.63, 95% CI 1.93-6.85, P<0.001), higher cholesterol (every 1 mmol/L increase, HR=1.51, 95% CI 1.20-1.89, P<0.001), higher neutrophil-to-lymphocyte ratio (every 1 increase, HR=1.12, 95% CI 1.05-1.20, P=0.001), and lower albumin ( HR=0.89, 95% CI 0.82-0.95, P=0.001) were independent risk factors affecting the survival rates of PD patients. The C-index of the prediction cohort and the validation cohort were 0.815(95% CI 0.765-0.865) and 0.804(95% CI 0.744-0.864, respectively). Both internally and externally verified calibration curves showed that the predicted results were close to the actual survival rates. Conclusion:Based on age, blood total cholesterol level, stroke history, and NLR, the prognosis prediction model of peritoneal dialysis patients established with nomogram can help predict the 1-year and 3-year survival rates of peritoneal dialysis patients.

Effect of telmisartan on expression of metadherin in the kidney of mice with unilateral ureter obstruction / 南方医科大学学报

OBJECTIVE@#To explore the effect of telmisartan on the expression of metadherin in the kidney of mice with unilateral ureter obstruction.@*METHODS@#Eighteen male C57 mice were randomized into sham-operated group, model group and telmisartan treatment group. In the latter two groups, renal interstitial fibrosis as the result of unilateral ureter obstruction (UUO) was induced by unilateral ureteral ligation with or without telmisartan intervention. Renal pathological changes of the mice were assessed using Masson staining, and immunohistochemistry and Western blotting were used to detect the expression of extracellular matrix proteins and metadherin in the kidney of the mice. In the experiment, cultured mouse renal tubular epithelial cells (mTECs) were stimulated with transforming growth factor-β1 (TGF-β1) and transfected with a siRNA targeting metadherin, and the changes in the expressions of extracellular matrix proteins and metadherin were detected using Western blotting.@*RESULTS@#The expressions of extracellular matrix proteins and metadherin increased significantly in the kidney of mice with UUO ( < 0.05). Intervention with telmisartan significantly lowered the expressions of extracellular matrix proteins and metadherin and alleviated the pathology of renal fibrosis in mice with UUO ( < 0.05). In cultured mTECs, siRNA-mediated knockdown of metadherin obviously reversed TGF-β1-induced increase in the expressions of extracellular matrix proteins and metadherin.@*CONCLUSIONS@#Telmisartan can suppress the production of extracellular matrix proteins and the expression of metadhein to attenuate UUO-induced renal fibrosis in mice.

Shenkang pill down-regulates AOPP-induced expression of inflammatory factor MCP-1 via a p38MAPK/NF-κB-dependent mechanism / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of the serum of rats fed with Shenkang pill in regulating monocyte chemoattractant protein 1 (MCP-1) expression induced by advanced oxidation protein products (AOPP) in mouse podocyte clone 5 (MPC5) and explore the underlying mechanism.</p><p><b>METHODS</b>MPC5 cultured in vitro were incubated for different time lengths in the presence of different concentrations of serum of rats medicated with Shenkang pill, and the cell proliferation was assessed using MTT assay. In MPC5 treated with AOPP prior to exposure to the rat serum, the changes in the protein expressions of p38MAPK and IκBα were examined with Western blotting, NF-κB p65 nuclear translocation was analyzed with immunofluorescence assay, and MCP-1 expression in the supernatant was determined using ELISA kits.</p><p><b>RESULTS</b>The medicated rat serum time- and concentration-dependently promoted the proliferation of MPC5, with the optimal serum concentration of 5% and incubation time of 24 h. AOPP significantly increased MCP-1 expression in the cell supernatant in a time-and concentration-dependent manner; pretreatment with SB203580 (a p38 inhibitor) or parthenolide (a NF-κB inhibitor) significantly decreased MCP-1 expression, and treatment with the medicated serum significantly decreased AOPP-induced MCP-1 expression. AOPP concentration-dependently increased the protein expression of P-p38 but decreased that of IκBα. Both the medicated serum and SB203580 increased IκBα protein in AOPP-induced cells, but the effect was more obvious with the medicated serum. The medicated serum also decreased NF-κB p65 nuclear translocation in AOPP-induced MPC5.</p><p><b>CONCLUSION</b>Shenkang pill-medicated serum can decrease AOPP-induced expression of MPC-1 in MPC5 by regulating p38MAPK/NF-κB to mediate its anti-inflammatory effect. This finding provides a new theoretical basis for the application of Shenkang pill to treat diabetic nephropathy.</p>

Effects of parthenolide on high glucose-induced cell proliferation, NF-κB activation and MCP-1 expression in rat mesangial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effects of parthenolide (PTL) on high glucose-stimulated cell proliferation, NF-κB activation and monocyte chemoattractant protein-1 (MCP-1) expression in rat mesangial cells (MCs).</p><p><b>METHODS</b>MCs were cultured in normal glucose (5.6 mmol/L), high glucose (30 mmol/L), or high glucose with PTL. MTT assay was used to detect the cell proliferation. MCP-1 content in the supernatant was measured by ELISA, and the level of IκBα was detected by Western blotting to reflect NF-κB activity. EMSA method was used to measure the activation of NF-κB.</p><p><b>RESULTS</b>MC proliferation, MCP-1 expression and NF-κB activation were significantly enhanced and the expression of NF-κB-binding protein IκBα was obviously reduced in cells cultured in high glucose. Application of PTL obviously abolished the effects of high glucose.</p><p><b>CONCLUSION</b>PTL can suppress high glucose-stimulated NF-κB activation and MCP-1 expression in rat MC. These data provide a theoretical basis for the clinical application of PTL in prevention and control of diabetic nephropathy.</p>

Incidence and influencing factors of aldosterone breakthrough during therapy with angiotensin Ⅱ receptor blockers alone,or combined with angiotensin-converting enzyme inhibitors in patients with non-diabetic nephropathy / 中华肾脏病杂志

Objective To investigate the incidence and influencing factors of aldosterone breakthrough during therapy with angiotensin Ⅱ receptor blockers (ARB) alone,or combined with angiotensin-converting enzyme inhibitors (ACEI) in Chinese patients with non-diabetic nephropathy.Methods A total of 144 patients with non-diabetic nephropathy were treated with ARB or combination therapy of ACEI and ARB for a mean follow-up period of 12 months.Aldosterone breakthrough was determined according to the change of plasma aldosterone concentration before and after treatment during 6-month and 12-month ACEI/ARB treatment.Results In 6 months,aldosterone breakthrough occurred in 21 patients,corresponding to 14.58％,while in 12 months,occurred in 39 patients,corresponding to 27.08％.Although the overall urinary protein excretion (UPE) decreased after treatment in both groups (P＜0.05),non-breakthrough group had a more remarkable reduction in UPE (P＜0.05).Univariate Logistic regression demonstrated that risk factors of aldosterone breakthrough included pre-treatment values of UPE (OR=3.643,P=0.073) and eGFR (OR=0.980,P=0.025).Multivariate Logistic model revealed pre-treatment values of eGFR was positively associated with aldosterone breakthrough (OR=0.980,P=0.025).Conclusions The incidence of the aldosterone breakthrough increases with duration of treatment.The patients with aldosterone breathrough have higher level of UPE,and enhanced decline in eGFR.Pretreatment value of eGFR is independent risk factor of aldosterone breakthrough.

Cloning and sequence analysis of a new cathepsin L-like cysteine proteinase gene from Ditylenchus destructor / 生物工程学报

The Cathepsin L-like cysteine proteinase genes (cpls) are multifunction genes related to the parasitic abilities of plant parasitic nematodes. A new cathepsin L-like cysteine proteinase gene (Dd-cpl-1) (GenBank Accession GQ 180107) was cloned from Ditylenchus destructor by RT-PCR and RACE. The cDNA sequence consisted of a 1 131 bp open reading frame (ORF) encoding 376 amino acid residues that were franked by a 29 bp 5'-untranslated region (UTR) and a 159 bp 3'-UTR. Genomic sequence analysis showed that Dd-cpl-1 contained 7 introns, obeyed the GT/AG rule in the splice-site junctions. Homology analysis showed that the identity was 77% between Dd-cpl-1 deduced protein Dd-CPL-1 and cathepsin L-like cysteine proteinase of Bursaphelenchus xylophilus. Multi-sequence alignment indicated that there were the catalytic triad (Cys183, His322 and Asn343) and two motifs ERFNIN motif and GNFD motif in deduced protein Dd-CPL-1. Cysteine proteinases phylogenetic analysis showed that Dd-cpl-1 belonged to the sub-clade of cathepsin L-like cysteine proteinases.

Effect of compound preparation of huangqi and dahuang on proliferation and secretion of extracellular matrix in mesangial cells of cultured rats / 中国组织工程研究

BACKGROUND: Diabetic nephropathy is one of the most serious vascular complications of diabetes mellitus. Compound preparation of huangqi and dahuang, a traditional Chinese medicine, has been used to preventing or treating diabetic nephropathy for several years, and has a certain protective effect on the kidney of diabetes mellitus patients. But its exact mechanism remains unknown and needs to be studied more.OBJECTIVE: To investigate the effect of compound preparation shenkang wan on the proliferation and secretion of extracellular matrix in cultured rat mesangial cells induced by high glucose.DESIGN: Randomized and controlled study.SETTING: Center of Integrated Traditional and Western Nephrology of Zhujiang Hospital and Medicine Department of Nanfang Hospital, Southern Medical University.MATERIALS: The serum pharmacological experiment was performed in Animal Experimental Center of Southern Medical University in A pril 2005.The cell culture experiment was conducted in Cell culture room of Southern Medical University from April 2005 to July 2005. Totally 16 normal Wistar male rats, weighted varied from 190 g to 220 g, were used in the study.METHODS: Sixteen normal Wistar male rats were randomly divided into 4 groups: normal serum group, capoten group, shenkang wan group (high dose and low dose); shenkang wan was mainly constituted of huangqi,dahuang, leech, gordon guryale seed and corn stigma and made in Pharmacy Department of Zhujiang Hospital of Nanfang Medical University, agent number: 20031214). ① The rats in capoten group and high and low dose shenkang wan group were given the corresponding drugs respectively according to 5 mg/kg, 2.4 g/kg, 1.2 g/kg weight. The rats in normal serum group were given the same volume water. After treated 7 days, all rats were hocused and separated medication serum. ② Mesangial cell was cultured in vitro with different concentrations of glucose (10, 20, 30 and 40 mmol/L).The proliferation of mesangial cell was observed with the methyl-thiazoltelrazolium colorimetric assay at 24, 48, 72 hours and 96 hours. ③ Then the cultured mesangial cells were divided into six subgroups :Low glucose control group (10 mmol/L glucose), high glucose group (30 mmol/L glucose);normal serum group (30 mmol/L glucose); capoten group (30 mmol/L glucose); shenkang wan group (high dose and low dose, 30 mmol/L glucose).After cultured 72 hours, the proliferation of mesangial cell was detected with the methyl-thiazol-telrazolium colorimetric assay, the secretion and mRNA gene expression of fibronetin levels in mesangial cell were respectively detected by enzyme linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR) method.MAIN OUTCOME MEASURES: ①Proliferation of mesangial cell induced by different concentrations glucose. ② Proliferation and secretion and mRNA gene expression of fibronectin in every group.RUSULTS: ① Effect of different concentrations glucose on the prolifera-tion of mesangial cell: Compared with low concentrations glucose(10 mmol/L), 20 mmol/L glucose could accelerate the proliferation ofmesangial cell during 96 hours experiment period, but only had a statisti-cally significant difference at 72 and 96 hours (P ＜ 0.05). 30 mmol/L glu-cose could significantly accelerate the proliferation of mesangial cell thanthat of 10 mmol/L glucose from 24 hours to 96 hours (P ＜ 0.05 or P ＜ 0.01),and this effect was increasing with time in 72 hours and reduced after 72hours. 40 mmol/L glucose could significantly increase the proliferation ofmesangial cell than of low concentrations glucose in 48 hours (P ＜ 0.05),and this effect was reduced after 48 hours and even conversed to restraineffect. ② Effect of different medication serum on the proliferation ofmesangial cell: The optical density value in high glucose group is obviouslyhigher than that of low glucose control group (P ＜ 0.01). Compared withhigh glucose group, the optical density value in capoten, shenkang wangroup (high dose and low dose) was decreased markedly (P ＜ 0.01 or P＜ 0.05). While the optical density value in normal serum group was showedno difference with the high glucose group (P ＞ 0.05). ③ Effect of differentmedication serum on secretion of fibronectin in mesangial cell: Content offibronectin in high glucose group was increased more markedly than that oflow glucose group (P ＜ 0.01). Compared with high glucose group, contentof fibronectin in capoten and shenkang wan group (high dose and low dose)was showed a significantly decrease (P ＜ 0.01 or P ＜ 0.05), while contentof fibronectin in normal serum group was showed no difference with thehigh glucose group (P ＞ 0.05). ④ Effect of different medication serum onexpression of fibronectin mRNA in mesangial cell: The optical density val-ue of fibronectin strip in high glucose group was brighter than that in lowglucose group and the ratio of it and β-actin were increased markedly too(P ＜ 0.01). Compared with high glucose group, the optical density value offibronectin strip in capoten and shenkang wan group (high dose and lowdose) was showed a significantly decrease and the ratio of it and β-actinwas reduced distinctly too (P ＜ 0.01), while the ratio of it and β-actin innormal serum group was showed no difference (P ＞ 0.05).CONCLUSION: High glucose could accelerate proliferation, increase thesecretion and mRNA gene expression of fibronectin in mesangial cell,while shenkang wan could inhibit proliferation and secretion of the extra-cellular matrix in mesangial cell induced by high glucose.

Effect of Maiditong for injection on coagulative and fibrionlytic system in diabetic nephropathy / 中成药

AIM: To investigate the clinical effect of Maiditong for injection(Herba Erigerontis) on coagulative and fibrionlytic system in diabetic nephropathy(DN). METHODS: 59 patients definitely diagnosed as diabetes type 2 DN were randomly divided into treatment and control groups.The treatment group were treated with Maiditong for injection,and the control group were treated with of Compound Danshen Injection.The 24 h proteinuria and vWF:Ag、Fbg、PF_(1+2)、FPA、D-dimer、AT-Ⅲ:A、tPA、PAI-1、PIC、PLG were tested before and after the therapies. RESULTS: After one therapy course(2 weeks),in the treatment group the 24 h proteinuria decreased obviously(P

Effect of irbesartan on nephrin expression in the podocyte of early diabetic nephropathy rats / 中国病理生理杂志

AIM: To investigate the expression of the nephrin in podocyte of the diabetic nephropathy(DN) rats and the mechanism of irbesartan-induced renal protection.METHODS: The DN model was established by a single injection of streptozotocin(STZ),and DN rats were randomly divided into 2 groups: model group and irbesartan treatment group.In addition,the normal rats served as a normal control group. All the rats were received daily gavage respectively for 8 weeks. The urinary protein quality in 24 hours,body weight(BW),kidney weight (KW),KW/BW,glucemia,urea nitrogen,creatinine,total cholesterol, triacylglycerol were detected with correlative methods and the pathological changes of kidney were also detected with optic microscope and transmission electron microscope.The expression of nephrin in podocyte were detected by immunohistochemistry. RESULTS: In DN rats, irbesartan reduced the urinary protein quality in 24 hours (P