Publications by authors named "Yaling Bai"

26 Publications

  • Page 1 of 1

Benefit of an Internet-Based Management System among Hemodialysis Patients at the Risk of Intradialytic Hypotension and Muscle Cramps: A Controlled before and after Study.

Blood Purif 2021 Sep 15:1-8. Epub 2021 Sep 15.

Department of Nephrology, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Hebei Clinical Research Center for Chronic Kidney Disease, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Background: The purpose of this study was to observe the impact of an internet-based management system on the incidence of intradialytic hypotension (IDH) and muscle cramps in hemodialysis patients.

Methods: The patients, who underwent maintenance hemodialysis in the center from January 2018 to June 2020, were recruited and divided into the pre-intervention group (before operation of the internet-based hemodialysis management system, from January 2018 to December 2018) and intervention group (after operation of the system, from June 2019 to June 2020). The clinical outcomes were compared between groups.

Results: The compound endpoint of >1 IDH or muscle cramps happened in 182 patients (61.7%) in the pre-intervention group and 99 participants (30.8%) in the intervention group (relative risk [RR] = 0.50 [95% confidence interval [CI], 0.42; 0.60]). IDH occurred in 122 patients (1-5 episodes in 47 patients, 6-10 episodes in 25 patients, and >10 episodes in 50 patients) and 33 patients (30 patients had 1-5 episodes and 3 patients had 6-10 episodes) before and after execution of the internet-based management system, respectively (RR = 0.25 [95% CI, 0.18; 0.35]). The incidence of muscle cramps was significantly decreased (RR = 0.57 [95% CI, 0.45; 0.73]) after the implementation of the system, and the number of patients with 6-10 episodes dropped from 10 to 1. Multivariate analyses also showed significantly lower RRs in the intervention group: 0.29 ([95% CI, 0.20; 0.41]) for IDH and 0.58 ([95% CI, 0.45; 0.74]) for muscle cramps. Compared with the pre-intervention, participants in the intervention group had a large improvement in self-management (p < 0.001) and self-efficacy (p < 0.001).

Conclusion: The study found that the internet-based hemodialysis management system was effective in reducing the IDH and muscle cramp events and improving self-management. It provided a significant implication for the development and application of internet-based programs in hemodialysis management.
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http://dx.doi.org/10.1159/000518695DOI Listing
September 2021

MicroRNA-103a regulates the calcification of vascular smooth muscle cells by targeting runt-related transcription factor 2 in high phosphorus conditions.

Exp Ther Med 2021 Sep 19;22(3):1036. Epub 2021 Jul 19.

Department of Nephrology, The Fourth Hospital of Hebei Medical University, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Hebei Clinical Research Center for Chronic Kidney Disease, Shijiazhuang, Hebei 050011, P.R. China.

Vascular calcification, such as atherosclerosis, is a serious complication of chronic kidney disease that is characterized by tunica media calcification, and has gained increasing attention from researchers. The commonly observed association between vascular calcification and osteoporosis suggests a link between bone and vascular disorders. As microRNAs (miRNAs) have a wide range of gene regulation functions, such as cell proliferation, apoptosis, stress and transdifferentiation, the current study aimed to determine whether miRNAs play a vital role in the calcification and osteoblastic differentiation of rat thoracic aorta vascular smooth muscle cells (VSMCs). Gene expression analysis was performed on seven miRNAs (miR-29a, -30b, -103a, -125b, -133a, -143 and -211) that maybe potentially involved in the differentiation of smooth muscle cells into osteoblastic cells. The results showed that the levels of miR-29a, -30b, -103a, -125b and -143 were markedly reduced in the VSMC calcification model, particularly miR-103a, whereas runt-related transcription factor 2 () expression was increased. Furthermore, it was found that the expression of was significantly decreased following the upregulation of miR-103a, and that the expression of was significantly increased by downregulating miR-103a in VSMCs. Therefore, it was concluded that miR-103a plays a notable role in the transdifferentiation of the VSMCs in high phosphorus-induced calcification by targeting the regulation of , and may therefore constitute a new target for the diagnosis and treatment of vascular calcification.
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http://dx.doi.org/10.3892/etm.2021.10468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343701PMC
September 2021

The intermediate-conductance calcium-activated potassium channel KCa3.1 contributes to alkalinization-induced vascular calcification in vitro.

J Clin Lab Anal 2021 Aug 27;35(8):e23854. Epub 2021 Jul 27.

Hebei Clinical Research Center for Chronic Kidney Disease, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Departments of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Objective: In order to find new strategies for the prevention of vascular calcification in uremic individuals especially treated by dialysis and develop novel therapeutic targets in vascular calcification, we explore the role of KCa3.1 in alkalinization-induced VSMCs calcification in vitro.

Method: Rat VSMCs calcification model was established by beta-glycerophosphate (β-GP, 10 mM) induction. The pH of Dulbecco's modified Eagle's medium (DMEM) was adjusted every 24 h with 10 mM HCl or 10 mM NaHCO . The mineralization was measured by Alizarin Red staining and O-cresolphthalein complex one method. mRNA and protein expression were detected by RT-PCR and Western blot or immunofluorescence. Ca2+ influx was measured by Elisa.

Result: The results indicated that alkalization induced an increase in Ca2+ influx to enhance VSMCs calcification. Furthermore, the increase of calcification was associated with the expression of KCa3.1 via advanced expression of osteoblastic differentiation markers alkaline phosphatase (ALP) and Runt-related transcription factor 2 (Runx2). Blocking KCa3.1 with TRAM-34 or shRNA vector can significantly lowered the effects of calcification in the activity of ALP and Runx2 expression.

Conclusion: Together all, our studies suggested that alkalinization can promote vascular calcification by upregulating KCa3.1 channel and enhancing osteogenic/chondrogenic differentiation by upregulating Runx2. The specific inhibitor TRAM-34 and KCa3.1-shRNA ameliorated VSMCs calcification by downregulating KCa3.1.
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http://dx.doi.org/10.1002/jcla.23854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373358PMC
August 2021

The safety outcomes of sodium-glucose cotransporter 2 inhibitors in patients with different renal function: A systematic review and meta-analysis.

Nutr Metab Cardiovasc Dis 2021 05 13;31(5):1365-1374. Epub 2021 Feb 13.

Departments of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, PR China. Electronic address:

Aims: We aimed to assess whether the safety outcomes exerted by sodium-glucose cotransporter 2 (SGLT2) inhibitors were associated with different renal function at baseline.

Data Synthesis: We searched randomized controlled trials comparing SGLT2 inhibitors with placebo in participants simultaneously involving the entire range of estimated glomerular filtration rate (eGFR) levels at baseline in one study. According to eGFR, we divided the population into two subgroups with eGFR <60 ml/min/1.73 m and eGFR≥60 ml/min/1.73 m. Data from the CANVAS program, CREDENCE, EMPA-REG OUTCOME, DECLARE-TIMI 58, DAPA-HF, and EMPA-REG RENAL were included. SGLT2 inhibitors significantly reduced the risk of all serious adverse events (HR 0.91 [95% CI 0.87 to 0.95], p < 0.001) and acute kidney injury (HR 0.74 [95% CI 0.64 to 0.85], p < 0.001). Except for high risk of genital infection, SGLT2 inhibitors did not increase the risk of amputation, fracture, hyperkalemia, hypoglycemia, volume depletion, or urinary tract infection. Further analyses showed that these safety outcomes were similar between subgroups (p-interaction > 0.05). For osmotic diuresis, SGLT2 inhibitors significantly increased the risk by 75% (p = 0.036), and subgroup analyses showed that this effect was completely attributed to the increase in patients with eGFR ≥60 ml/min/1.73 m (p-interaction<0.001).

Conclusion: The indication of no risk of osmotic diuresis in patients with eGFR<60 ml/min/1.73 m and the consistency of other safety outcomes across different baseline renal function may allow additional individuals to safely use SGLT2 inhibitors.
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http://dx.doi.org/10.1016/j.numecd.2021.02.006DOI Listing
May 2021

Nephrotoxicity in patients with solid tumors treated with anti-PD-1/PD-L1 monoclonal antibodies: a systematic review and meta-analysis.

Invest New Drugs 2021 Jun 6;39(3):860-870. Epub 2021 Jan 6.

Department of Nephrology, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Hebei Clinical Research Center for Chronic Kidney Disease, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, People's Republic of China.

Background Programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) have dramatically improved cancer therapy for many patients. Adverse kidney effects have been found to be an important complication but have unclear mechanisms. Methods We searched Embase, PubMed, and the Cochrane Library to identify potential eligible studies. All included studies were randomized controlled trials (RCTs) examining patients with solid tumors treated with anti-PD-1/PD-L1 monoclonal antibodies (mAbs) and/or chemotherapy. The relative risk (RR) was used to assess the risk of nephrotoxic events. Results We included 27 clinical trials (15,063 patients). Compared with chemotherapy, the RR of all-grade nephritis was significantly increased with anti-PD-1/PD-L1 mAbs (RR = 2.77, 95% CI: 1.09-6.99, P = 0.03). Furthermore, anti-PD-1/PD-L1 mAbs plus chemotherapy can significantly increase the RR of all-grade nephritis (RR = 2.99, 95% CI: 1.07-8.35, P = 0.04). There was also a significant increase in the RRs of all-grade increased blood creatinine (RR = 1.88, 95% CI: 1.24-2.86, P = 0.003) and acute kidney injury (AKI) (RR =3.35, 95% CI: 1.48-7.60, P = 0.004). Conclusions Anti-PD-1/PD-L1 mAbs can significantly increase nephrotoxicity in patients with solid tumors, especially when combined with chemotherapy. During the application of these drugs, we should remain aware of nephrotoxicity for better efficacy. Trial registration number and date of registration Not applicable.
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http://dx.doi.org/10.1007/s10637-020-01039-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068624PMC
June 2021

Identification of a genome-wide serum microRNA expression profile as potential noninvasive biomarkers for chronic kidney disease using next-generation sequencing.

J Int Med Res 2020 Dec;48(12):300060520969481

Department of Nephrology, The Fourth Hospital of Hebei Medical University, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Hebei Clinical Research Center for Chronic Kidney Disease, Shijiazhuang, China.

Objective: To identify serum microRNAs (miRNAs) as potential non-invasive biomarkers for patients with chronic kidney disease (CKD).

Methods: We collected serum samples from healthy controls, CKD stage 1 (CKD1), and stage 5 (CKD5) patients with primary glomerulonephritis (GN), screened differentially expressed miRNAs (DEMs) using next-generation sequencing (NGS), and confirmed the sequencing data using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).

Results: We identified 20 and 42 DEMs in the CKD1 and CKD5 patients compared with the controls, respectively, and 70 DEMs in the CKD5 compared with the CKD1 patients. The qRT-PCR results showed that miR-483-5p was up-regulated in the CKD1 and CKD5 patients compared with controls (fold change = 2.56 and 18.77, respectively). miR-363-3p was down-regulated in the CKD5 patients compared with the controls and CKD1 patients (fold change = 0.27 and 0.48, respectively).

Conclusion: We identified a genome-wide serum miRNA expression profile in CKD patients, and serum miR-483-5p and miR-363-3p may act as potential diagnostic biomarkers for CKD.
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http://dx.doi.org/10.1177/0300060520969481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739098PMC
December 2020

Menaquinone-4 modulates the expression levels of calcification-associated factors to inhibit calcification of rat aortic vascular smooth muscle cells in a dose-dependent manner.

Exp Ther Med 2018 Oct 27;16(4):3172-3178. Epub 2018 Jul 27.

Department of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.

Vascular calcification (VC) caused by chronic kidney disease (CKD)-mineral and bone disorder is a common complication of CKD. Recent studies have demonstrated that menaquinone-4 (MK-4) is negativly associated with VC in patients with CKD. Furthermore, we have previously shown that runt-related transcription factor 2 (Runx2) is important in the phenotypic transformation process of rat vascular smooth muscle cells (VSMCs), which is the key step for the development of VC. The present study investigated the influence of MK-4 on the phenotypic transformation process of rat VSMCs in order to illustrate its role in the process of VC. Calcification assays were perfomed to access the calcified degree of rat VSMCs. Additionally, the genes and proteins related to phenotypic transformation were measured by reverse transcription-polymerase chain reaction and western blotting methods. It was revealed that calcium deposition in the cells was evidently increased with an addition of β-glycerophosphate (β-GP) and could be completely prevented by co-incubation with MK-4 in a dose-dependent manner. Furthermore, the expression of Runx2 in the β-GP-induced VSMCs was inhibited by MK-4. It was also revealed that the expression of SMAD1 and bone morphogenetic protein (BMP)-2 were decreased in the β-GP-induced VSMCs treated with MK-4 in a dose-dependent manner; however, the expression of SMAD7 was increased in the β-GP-induced VSMCs treated with MK-4 in a dose-dependent manner. These observations suggest that MK-4 reduces mineralization by regulating the BMP-2 signaling pathway in order to attenuate the expression of Runx2.
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http://dx.doi.org/10.3892/etm.2018.6535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125841PMC
October 2018

Extracellular acidosis suppresses calcification of vascular smooth muscle cells by inhibiting calcium influx via L-type calcium channels.

Clin Exp Hypertens 2018 8;40(4):370-377. Epub 2018 Feb 8.

a Departments of Nephrology , The Fourth Hospital of Hebei Medical University , Shijiazhuang , P. R. China.

Vascular calcification such as arteriosclerosis, which is characterized by a calcification of the tunica media, is a severe complication of chronic kidney disease (CKD), contributing to the high prevalence of cardiovascular morbidity and mortality in patients with CKD. An essential step during the development of arteriosclerosis is the transdifferentiation/calcification of vascular smooth muscle cells (VSMCs), resembling osteogenesis. Metabolic acidosis, a common clinical manifestation in CKD, is known to decrease vascular calcification. To understand the underlying regulatory mechanisms of acidosis, we investigated whether the acidosis-decreased VSMC calcification involves altered signaling of the LTCC/Ca/Runx2 pathway. Vascular calcifications, calcium content, runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), L-type calcium channel (LTCC) β subunits, and calcium influx were measured in vivo or in vitro. Calcified nodules and calcium content increased either in aorta sections of vascular calcified rats or in VSMCs induced by β-GP. The expression of Runx2 and ALP activity markedly rose, accompanied by the increasing expression of LTCC β subunits and calcium influx. However, acidosis supplementation successfully attenuated VC and VSMC calcification and inhibited Runx2, ALP, LTCC β subunits, and calcium influx. In conclusion, acidosis significantly attenuated vascular calcification in association with downregulation of the LTCC/Ca/Runx2 pathway.
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http://dx.doi.org/10.1080/10641963.2017.1384482DOI Listing
August 2018

miR-502-mediated histone methyltransferase expression is associated with clear cell renal cell carcinoma risk.

Oncol Lett 2017 Dec 2;14(6):7131-7138. Epub 2017 Oct 2.

Department of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.

Genetic variants may affect the interactions between microRNAs (miRNAs/miRs) and their target genes by modulating their binding affinity or by creating, or destroying a miRNA-binding site. SET domain containing (lysine methyltransferase) 8 (SET8) is the sole lysine methyltransferase that catalyzes the monomethylation of histone H4 lysine 20, and is associated with tumor growth, invasion and metastasis. In the present study, the rs16917496 polymorphism within the miR-502 binding site of the SET8 mRNA 3' untranslated region (3'UTR) in patients with clear cell renal cell carcinoma (ccRCC) and healthy controls was genotyped. The CC genotype was associated with a decreased ccRCC risk compared with the CT [P=0.003; odds ratio (OR)=0.318; 95% confidence interval (CI), 0.146-0.691], TT (P=0.011; OR=0.402; 95% CI, 0.197-0.819) and CT+TT (P=0.004; OR=0.370; 95% CI, 0.186-0.736) genotypes. The CC genotype was associated with reduced SET8 expression based on immunostaining of ccRCC tissue. Low SET8 protein levels were negatively associated with tumor-node-metastasis staging in patients with ccRCC according to the size of tumor and lymph node metastases. -knockdown inhibited renal carcinoma 786-O cell proliferation, migration and invasion. c-Myc and matrix metalloproteinase-7 mRNA expression were downregulated upon -knockdown in renal carcinoma 786-O cells. These data indicated that SET8 may be a functional tumor promoter and that its activation, which is partially regulated by changing the miR-502 and 3'UTR binding affinity, may serve an important role in ccRCC development.
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http://dx.doi.org/10.3892/ol.2017.7115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727589PMC
December 2017

Effects of extracellular acid stimulation on rat vascular smooth muscle cell in Gas6/Axl or PI3K/Akt signaling pathway.

Clin Exp Hypertens 2016;38(5):451-6. Epub 2016 Jun 30.

a Department of Nephrology , The Fourth Affiliated Hospital of Hebei Medical University , Shijiazhuang City , Hebei Province , China.

Recent studies have indicated that extracellular acid stimulation inhibited the calcification of vascular smooth muscle cells (VSMCs). Cell apoptosis played an important role in the occurrence and development of vascular calcification. We further explored the effects of Gas6/Axl or PI3K/Akt signaling pathway on the inhibition of rat VSMCs calcification in response to extracellular acid stimulation. Our study demonstrated that a high concentration of phosphorus induced apoptosis and calcification of VSMCs, decreased expression of Axl, and reduced phosphorylation of Akt. Stimulation of extracellular acid counteracted the effects as above by increasing the expression of Axl and Akt phosphorylation and decreasing the expression of activated Caspase3, which thereby decreased cell apoptosis and calcification. Moreover, the effects can be attenuated by PI3K inhibitor. Our study proved that extracellular acid stimulation played a vital role in the inhibition of rat VSMCs calcification and apoptosis in Gas6/Axl or PI3K/Akt signaling pathway.
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http://dx.doi.org/10.3109/10641963.2016.1163366DOI Listing
December 2016

[Risk factors for coronary artery calcification in patients with end-stage renal disease].

Zhonghua Yi Xue Za Zhi 2015 Oct;95(38):3133-7

Department of Nephrology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.

Objective: To explore risk factors for coronary artery calcification (CAC) inpatients with end-stage renal disease (ESRD).

Methods: A total of 53 ESRD patients undergoing regular hemodialysis (3 times a week) from August 2014 to March 2015 in the Fourth Hospital of Hebei Medical University were enrolled in the study. The patients were divided into the negative control group (13 cases) and three positive groups (11 mild calcification cases, 12 moderate calcification cases and 17 severe calcification cases) based on coronary artery calcification score (CACs). Clinical data of all patients at study entry were collected. Arterial blood samples were also collected at the start of the first hemodialysis (HD) session of the week to measure the levels of serum albumin, uric acid, calcium (Ca), phosphorus (P), magnesium, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), C reactive protein (CRP), beta-2 microglobulin (β2-MG), free parathyroid hormone (iPTH), alkaline phosphatase, fibrinogen, hemoglobin (HGB) and ferritin. Meanwhile, levels of blood pH were detected after collecting pre- and post-HD blood samples to calculate ΔpH (post-HD pH subtracted pre-HD pH). Logistic regression analysis was performed to analyze the correlation of CACs with clinical data and previously-reported blood biochemical indicators, followed by analysis of the incidence of CAC and influential factors in ESRD patients.

Results: Severity of CAC was positively correlated with age (r=0.269), HD duration (r=0.341), serum calcium (r=0.358), serum phosphorus (r=0.186) and pre-HD pH (r=0.275), but negatively correlated with serum albumin (r=-0.192) and ΔpH (r=-0.302), all P<0.05. Logistic regression analysis revealed that age, HD duration, serum phosphorus level and ΔpH were independent risk factors for CAC in ESRD patients (P<0.05). In CAC positive groups, CAC was predominantly involved in the left anterior descending artery (P<0.05, P<0.01 and P<0.01 in mild, moderate and severe calcification group, respectively).

Conclusions: CAC in ESRD patients seems to be affected by multiple factors, such as age, HD duration, serum phosphorus level and ΔpH. Moreover, ΔpH affects CAC mainly by pre-HD pH. Furthermore, left anterior descending artery is predominantly affected by CAC in ESRD patients.
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October 2015

Magnesium prevents β-glycerophosphate-induced calcification in rat aortic vascular smooth muscle cells.

Biomed Rep 2015 Jul 27;3(4):593-597. Epub 2015 May 27.

Department of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.

Vascular calcification (VC), in which high serum phosphate plays a critical role, is one major problem in patients with chronic kidney disease. Clinical studies report that magnesium has a protective effect on VC. However, the studies regarding the impact of high serum magnesium on VC at a cellular level are few and require further investigation. Therefore, the present study explored the effect of magnesium on calcification induced by β-glycerophosphate (BGP) in rat aortic vascular smooth muscle cells (RAVSMCs). In the present study, the addition of magnesium decreased calcium deposition, which was increased by BGP. Higher magnesium levels inhibited BGP-induced alkaline phosphatase (ALP) activity and decreased the expression of core-binding factor α-1 (Cbfα1). In conclusion, higher magnesium levels prevented BGP-induced calcification in RAVSMCs and inhibited the expression of Cbfα1 and ALP. Thus, magnesium is influencing the expression of Cbfα1 and ALP associated with VC and may have the potential to serve as a role for VC in clinical situations.
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http://dx.doi.org/10.3892/br.2015.473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486886PMC
July 2015

Single-nucleotide polymorphism of the promoter is associated with the outcome of chronic kidney disease patients.

Biomed Rep 2015 Jul 26;3(4):588-592. Epub 2015 May 26.

Department of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.

Uromodulin (UMOD) is the most abundant protein secreted in urine and the mutated form of the gene is associated with UMOD-associated kidney disease (UAKD). Although UMOD accumulates in the kidney of UAKD patients, it is unclear whether this also occurred in the chronic kidney disease (CKD) patients. Therefore, the association of single-nucleotide polymorphisms (SNPs) in the promoter region of gene with the kidney survival time of CKD was investigated. The promoter region of the gene was sequenced for 111 CKD patients. The Kaplan-Meier method was used to identify the disease outcome associated with SNPs in the promoter region of the gene in CKD patients. The Cox proportional hazard model was used to identify risk factors for the kidney survival time of CKD. SNPs in reference to GenBank accession NG-000016 were detected at 23 sites of the 481-bp in the UMOD promoter region from the CKD patients and the healthy controls. The 6 SNPs with minor allele frequency >5% in the CKD patients or controls were used for disease risk and outcome analysis. The frequent allele rs13333226AA was associated with a shorter period of kidney survival time in CKD patients (P=0.005). The length of kidney survival time in CKD patients with the rs13333226AA genotype was significantly shorter than that of patients with the frequent allele rs13333226AG+GG (relative risk, 0.361; 95% confidence interval, 0.171-0.761; P=0.007). In conclusion, analysis of genetic polymorphisms in may help to identify the CKD patient subgroups at a high risk for a disease outcome, thereby helping to refine therapeutic decisions in CKD patients.
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http://dx.doi.org/10.3892/br.2015.471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487055PMC
July 2015

Alteration of type I collagen in the radial artery of patients with end-stage renal disease.

Am J Med Sci 2015 Apr;349(4):292-7

Department of Nephrology (YB, JZ, JX, LC, HZ, SZ), The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Background: Cardiovascular disease is the leading cause of death in chronic kidney disease. Extracellular matrix remodeling is implicated in atherosclerosis development. This study investigated the effects and possible mechanism of type I collagen expression on radial artery elasticity in patients with end-stage renal disease (ESRD).

Methods: Sixty-five patients receiving forearm arteriovenous fistula in the Fourth Hospital of Hebei Medical University from January 2010 to December 2012 were enrolled in the study. The echo-tracking technique was used to measure radial artery 1-point pulse wave velocity (PWVβ), and immunohistochemical staining was used to detect the expression of type I collagen and transcription factor CBFA1, a marker for calcification, in the radial artery. Uremic serum and serum from healthy volunteers of different concentrations were then used to treat the rat aortic vascular smooth muscle cells (VSMCs), reverse transcription polymerase chain reaction (PCR) was used to measure COL1A1 and CBFA1 transcription and a Western blot was performed to detect type I collagen expression in the rat aortic VSMCs.

Results: In patients with ESRD, increased COL1A1 expression was an independent risk factor for radial artery PWVβ (P < 0.05) and was positively associated with that of CBFA1 (r = 0.573, P < 0.001). In the rat aortic VSMCs, serum from patients with ESRD upregulated COL1A1 and CBFA1 transcription as well as type I collagen expression in a concentration-dependent manner (P < 0.05).

Conclusions: Type I collagen expression is an essential factor for radial artery elasticity dysfunction in patients with ESRD. Uremic toxins apparently induced a phenotypic transition of the rat aortic VSMCs, leading to increased type I collagen secretion and subsequent extracellular matrix remodeling.
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http://dx.doi.org/10.1097/MAJ.0000000000000408DOI Listing
April 2015

Magnesium modulates the expression levels of calcification-associated factors to inhibit calcification in a time-dependent manner.

Exp Ther Med 2015 Mar 26;9(3):1028-1034. Epub 2015 Jan 26.

Department of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.

Vascular calcification, a common complication in patients with chronic kidney disease, involves a variety of mechanisms associated with the regulation of calcification-associated factors. Previous clinical studies have indicated that magnesium is involved in the reduction of vascular calcification; however, the mechanism underlying this process remains unknown. The aim of the present study was to investigate the effects of magnesium on β-glycerophosphate (β-GP)-induced calcification and the underlying mechanisms. Primary rat vascular smooth muscle cells (VSMCs) were exposed to 10 mM β-GP in medium with or without the addition of 3 mM magnesium or 2-aminoethoxy-diphenylborate (2-APB; an inhibitor of magnesium transport), for a 14-day period. Calcium deposition and alkaline phosphatase (ALP) activity were measured by Alizarin red staining, quantification of calcium and enzyme-linked immunosorbent assay. The expression levels of core-binding factor α-1 (Cbfα1), matrix Gla protein (MGP) and osteopontin (OPN) were determined by reverse transcription-polymerase chain reaction or western blot analysis, following incubation for 0, 3, 6, 10 and 14 days with the different media. VSMC calcification and ALP activity was reduced significantly in the high-magnesium medium compared with the calcification medium, during the 14-day incubation. The magnesium-induced changes in the VSMCs included a β-GP-induced downregulation of Cbfα1 by day 3 of incubation, an effect that was gradually enhanced over the 14-day period. By contrast, magnesium produced notable increases in MGP and OPN expression levels, with an opposite pattern to that observed in the Cbfα1 expression levels. However, the addition of 2-APB appeared to inhibit the protective effect of magnesium on the VSMCs. Therefore, magnesium was able to effectively reduce β-GP-induced calcification in rat VSMCs by regulating the expression levels of calcification-associated factors in a time-dependent manner.
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http://dx.doi.org/10.3892/etm.2015.2215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4316900PMC
March 2015

Associations between polymorphisms of HOTAIR and risk of gastric cardia adenocarcinoma in a population of north China.

Tumour Biol 2015 Apr 5;36(4):2845-54. Epub 2014 Dec 5.

Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

As an important long noncoding RNA, Hox transcript antisense intergenic RNA (HOTAIR) is involved in the development and progression of various carcinomas. However, the role and genetic alterations of HOTAIR in gastric cardia adenocarcinoma (GCA) occurrence and progression have not been elucidated. We performed a case-control study in a population of north China to evaluate the possible association between haplotype-tagging SNPs (htSNPs) of the whole HOTAIR sequence and the risk of GCA as well as functional effect of the susceptibility single nucleotide polymorphism (SNP) rs12826786 on gene expression. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to examine the genotype of htSNPs in 515 GCA patients and 654 control subjects, and the quantitative real-time reverse transcription PCR (RT-PCR) method was used to examine the expression of HOTAIR in 102 GCA patients. A family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing GCA. Among three htSNPs of the HOTAIR gene (rs12826786 C>T, rs4759314 A>G, and rs10783618 C>T), only the T allele of rs12826786 was found to increase the risk of developing GCA and was associated with smoking habit and tumor-node-metastasis (TNM) stage. In addition, higher expression levels of HOTAIR were found in tumor tissues and rs12826786 SNP has a genotype-specific effect on HOTAIR expression. A high HOTAIR expression level was associated with poor GCA patients' survival. These results indicate that functional genotype alteration of rs12826786 SNP may influence the expression of HOTAIR, and HOTAIR may be a useful marker to predict the biological behavior of tumors and potentially a therapeutic target in GCA treatment.
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http://dx.doi.org/10.1007/s13277-014-2912-yDOI Listing
April 2015

Single nucleotide polymorphisms in the D-loop region of mitochondrial DNA is associated with the kidney survival time in chronic kidney disease patients.

Ren Fail 2015 Feb 3;37(1):108-12. Epub 2014 Nov 3.

Departments of Nephrology, The Fourth Hospital of Hebei Medical University , Shijiazhuang , PR China and.

Background: The mitochondrial displacement loop (D-loop) is known to accumulate mutations and SNPs at a higher frequency than other regions of mitochondrial DNA (mtDNA). We had identified chronic kidney disease (CKD) risk-associated SNPs in the D-loop of CKD patients previously. In this study, we investigated the association of SNPs in the D-loop of mtDNA with the kidney survival of CKD.

Methods: The D-loop region of mtDNA was sequenced for 119 CKD patients from the inpatient of the Fourth Hospital of Hebei Medical University. The Kaplan-Meier method was used to identify disease outcome-associated SNPs in the D-loop of CKD patients. The Cox proportional hazards model was used to identify risk factors for the kidney survival of CKD.

Results: In the present study, we identified 20 SNPs with a frequency higher than 5% and assessed the relationship of these SNPs with kidney survival time in CKD patients, a SNP of 146 was identified by log-rank test for statistically significant prediction of the kidney survival time. In an overall multivariate analysis, allele 146 was identified as an independent predictor of kidney survival time in CKD patients. The survival time of kidney in the CKD patients with 146C was significantly shorter than that of kidney in CKD patients with 146T (relative risk, 2.336; 95% CI, 1.319-3.923; p = 0.001).

Conclusion: SNPs in the D-loop can predict the kidney survival of CKD patients. Analysis of genetic polymorphisms in the mitochondrial D-loop can help to identify CKD patient subgroup at high risk of a poor disease outcome.
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http://dx.doi.org/10.3109/0886022X.2014.976132DOI Listing
February 2015

The 9-bp deletion at position 8272 in region V of mitochondrial DNA is associated with renal cell carcinoma outcome.

Mitochondrial DNA A DNA Mapp Seq Anal 2016 05 20;27(3):1973-5. Epub 2014 Oct 20.

a Departments of Nephrology and.

Mitochondrial DNA (mtDNA) is considered a mutation hotspot in various types of tumors, and mitochondrial DNA microsatellite instability (mtMSI) is associated with various cancers. We had previously identified cancer risk-associated MSIs in the D-loop region of mtDNA in renal cell carcinoma (RCC) patients. In the present study, we further investigated the association of MSIs in the non-D-loop region of mtDNA with cancer risk and outcome of RCC. Six microsatellite loci (5892, 8272, 8280, 8281, 8289, 9777) in the non-D-loop of mtDNA were assessed. The CCCCCTCTA at position 8272 was associated with cancer outcome in an overall multivariate analysis (relative risk, 1.599; 95%CI, 1.365-1.872; p < 0.001). mtMSI at position 8272 can therefore be used as an independent prognostic marker for RCC patients.
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http://dx.doi.org/10.3109/19401736.2014.971312DOI Listing
May 2016

Single nucleotide polymorphisms in the D-loop region of mitochondrial DNA and age-at-onset of patients with chronic kidney disease.

Chin Med J (Engl) 2014 ;127(17):3088-91

Department of Nephrology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.

Background: The mitochondrial displacement loop (D-loop) accumulates mutations and single nucleotide polymorphisms (SNPs) at a higher frequency than other regions of mitochondrial DNA (mtDNA). We previously identified disease risk-associated SNPs in the D-loop of chronic kidney disease (CKD) patients; in this study, we investigated the association of age-at-onset and D-loop SNPs in CKD patients.

Methods: The D-loop region of mtDNA was sequenced in 119 CKD patients attending the Fourth Hospital of Hebei Medical University between 2002 and 2008. The age-at-onset curve of the CKD patients was calculated using the Kaplan-Meier method at each SNP site, and compared using the log-rank test.

Results: The mean age of 119 CKD patients was (55.6±14.2) years, and 56.3% were males. The mean estimated glomerular filtration rate (eGFR) was (81.2±12.4) ml×min(-1)×1.73 m(-2), with 79.8% (n = 95) of patients having an eGFR <60 ml×min(-1)×1.73 m(-2). All participants had an eGFR >30 ml×min(-1)×1.73 m(-2). The age-at-onset for CKD patients who smoked was significantly lower than that of non-smoking CKD patients. The SNP sites of nucleotides 150C/T were identified for their association with age-at-onset using the log-rank test. The age-at-onset of patients with the minor allele T genotype was significantly lower than that of patients with the C genotype at the 150 SNP site (P = 0.010).

Conclusions: Genetic polymorphisms in the D-loop appear to be predictive markers for age-at-onset in CKD patients. Accordingly, the analysis of genetic polymorphisms in the mitochondrial D-loop may help identify CKD patient subgroups at high risk of early onset disease.
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April 2015

High EphA2 protein expression in renal cell carcinoma is associated with a poor disease outcome.

Oncol Lett 2014 Aug 28;8(2):687-692. Epub 2014 May 28.

Department of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.

The receptor tyrosine kinase, ephrin type-A receptor 2 (EphA2), is normally expressed at sites of cell-to-cell contact in adult epithelial tissues, however, recent studies have shown that it is also overexpressed in various types of epithelial carcinomas, with the greatest level of EphA2 expression observed in metastatic lesions. In the present study, the association between the expression of EphA2 and the outcome of RCC patients was assessed. The high expression level of EphA2 was identified by log-rank test for a statistically significant prediction of the RCC outcome. In an overall multivariate analysis, the high expression level of EphA2 was identified as an independent predictor of RCC outcome. The length of survival of the patients with high EphA2 expression was shorter than that of the patients with a low level of expression (relative risk, 2.304; 95% CI, 1.102-4.818; P=0.027). The analysis of the expression levels of EphA2 in tumor tissues may aid in the identification of the patient subgroup that are at a high risk of a poor disease outcome.
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http://dx.doi.org/10.3892/ol.2014.2196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4081399PMC
August 2014

Identification of sequence polymorphisms in the displacement loop region of mitochondrial DNA as a risk factor for renal cell carcinoma.

Biomed Rep 2013 Jul 22;1(4):563-566. Epub 2013 May 22.

Departments of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.

The accumulation of single-nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) may be associated with an increased cancer risk. In this case-control study, the SNPs in the mitochondrial D-loop of renal cell carcinoma (RCC) patients were identified and their association with cancer risk was evaluated. The minor alleles of nucleotides 16293A/G, 262A/G and 488T/C were associated with an increased risk, whereas the minor alleles of nucleotides 16298T/C and 16319G/A were associated with a decreased risk for RCC. Moreover, the nucleotides 16293, 262, 16298 and 16319 were identified as specifically associated with the risk of clear cell RCC (ccRCC), whereas 262 and 488 were specifically associated with papillary RCC and renal oncocytoma. In conclusion, SNPs in mtDNA are potential modifiers of RCC. The analysis of genetic polymorphisms in the mitochondrial D-loop may help identify the patient subgroups at a high risk of developing RCC.
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http://dx.doi.org/10.3892/br.2013.113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3917727PMC
July 2013

Association of sequence polymorphism in the mitochondrial D-loop with chronic kidney disease.

Ren Fail 2014 Jun 27;36(5):781-4. Epub 2014 Feb 27.

Department of Nephrology, The Fourth Hospital of Hebei Medical University , Shijiazhuang , P.R. China and.

Background: The mitochondrial displacement loop (D-loop) is known to accumulate mutations and single nucleotide polymorphisms (SNPs) at a higher frequency than other regions of mitochondrial DNA (mtDNA).

Methods: This is a case-control study. We sequenced SNPs in the D-loop of mtDNA and investigated their association with the risk of chronic kidney disease (CKD).

Results: A total of 144 SNPs referring to the positions of the Revised Cambridge Reference Sequence (rCRS) for mitochondrial genome were identified in a case-control study. The minor alleles of nucleotides 73G, 146C, 150T, 194T, 195C and 310C were associated with an increased risk for CKD patients.

Conclusion: Analysis of genetic polymorphisms in the mitochondrial D-loop can help identify the people who are at a high risk of developing chronic kidney disease. These SNPs can be considered as potential predictors for CKD.
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http://dx.doi.org/10.3109/0886022X.2014.890842DOI Listing
June 2014

Analysis of a single hemodialysis on phosphate removal of the internal fistula patients by mathematical and statistical methods.

Comput Math Methods Med 2013 24;2013:856897. Epub 2013 Dec 24.

Departments of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.

Chronic kidney disease related mineral and bone disease (CKD-MBD) is a worldwide challenge in hemodialysis patients. In china, the number of dialysis patients is growing but few data are available about their bone disorders. In the current study, we aimed to evaluate the effect of clinical factors on the serum phosphorus clearance in the 80 maintenance hemodialysis (MHD) patients. Six clinical factors were identified for their association with the serum phosphorus clearance using the analysis of Spearman's single linear correlation, including predialysis serum phosphate level, CRR, membrane surface area of the dialyzer, effective blood flow rate, the blood chamber volume, and hematocrit. In an overall multivariate analysis, pre-P, CRR, membrane SA, and Qb were identified as independent risk factors associated with the serum phosphorus clearance. In conclusion, HD could effectively clear serum phosphorus. The analysis of CRR might help to estimate serum phosphorus reduction ratio.
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http://dx.doi.org/10.1155/2013/856897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3884625PMC
August 2014

Single nucleotide polymorphisms in the D-loop region of mitochondrial DNA is associated with renal cell carcinoma outcome.

Mitochondrial DNA 2015 Apr 11;26(2):224-6. Epub 2013 Sep 11.

Department of Nephrology .

Accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) has been described in various types of cancers and might be associated with cancer risk and disease outcome. We identified 14 SNPs with a frequency higher than 5% and 5 SNPs associated with the risk of renal cell carcinoma (RCC) in a case-control study previously. In the present study, we assessed the relationship of these SNPs and the outcome of RCC patients, a SNP of 262C/T was identified by the log-rank test for statistically significant prediction of RCC survival. In an overall multivariate analysis, allele 262 was identified as an independent predictor of RCC outcome. The length of survival of patients with 262T was significantly shorter than that of patients with allele 262C (relative risk, 2.136, 95%CI, 1.863-2.449; p = 0.000). The analysis of genetic polymorphisms in the mitochondrial D-loop can help identify patients subgroup at high risk of a poor disease outcome.
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http://dx.doi.org/10.3109/19401736.2013.825772DOI Listing
April 2015

Single nucleotide polymorphisms in the mitochondrial displacement loop and age-at-onset of renal cell carcinoma.

Sci Rep 2013 ;3:2408

Departments of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

The accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) has been described in various types of cancers, and their association with cancer risk and disease outcome has been extensively identified. In the present study, we investigated the association between age-at-onset and SNPs in the mitochondrial D-loop using a population-based series of renal cell carcinoma(RCC). The SNP sites of nucleotides 16293A/G were identified for their association with age-at-onset using the log-rank test. The age-at-onset of patients with the minor allele G genotype was significantly lower than that of patients with the A genotype at the 16293 site (p < 0.001). Genetic polymorphisms in the D-loop are predictive markers of age-at-onset in RCC patients. Accordingly, the analysis of genetic polymorphisms in the mitochondrial D-loop may help identify RCC patient subgroups at high risk of early onset.
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http://dx.doi.org/10.1038/srep02408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740277PMC
February 2014

High ambient glucose levels modulates the production of MMP-9 and alpha5(IV) collagen by cultured podocytes.

Cell Physiol Biochem 2006 7;17(1-2):57-68. Epub 2006 Feb 7.

Division of Nephrology, Peking University First Hospital, Beijing, China.

Recent evidences have demonstrated an important role for glomerular visceral epithelial cell (podocyte) in the development and progression of diabetic nephropathy. We investigated the high-glucose (HG)-triggered signaling pathway and its role in matrix metalloproteinase (MMP) production in murine podocytes. The activity of 92-kDa (MMP-9) gelatinase, but not of 72 kDa (MMP-2), in an HG medium significantly increased during incubation of 2 to 3 days and decreased during incubation of more than 5 days revealed by Gelatin zymography. Opposite to the increases in MMP-9 activity, HG medium produced significant decreases in the protein levels of alpha5(IV) collagen. Changes in MMP-9 activity were associated with the same pattern as MMP-9 mRNA levels in podocytes exposed to HG media. HG medium rapidly activated ERK1/2 MAPK in podocytes. Moreover, ERK1/2 activation was required for HG-induced enhancement of MMP-9 activity and a decrease in the level of alpha5(IV) collagen. HG incubation rapidly induced an increase in the nuclear accumulation of Ets-1 protein. Blocking the ERK pathway suppressed HG-induced expression and nuclear accumulation of transcriptional factor Ets-1, and MMP-9 mRNA expression. We suggest that short- or long-term exposure to HG concentrations increases or decreases MMP-9 production and alpha5(IV) collagen expression in podocytes, this may contribute to the GBM abnormality caused by an imbalance in extracellular matrix (ECM) synthesis and degradation, and may play a critical role in the pathogenesis of proteinuria in diabetic nephropathy.
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http://dx.doi.org/10.1159/000091464DOI Listing
April 2006
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