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Netrin-1 works with UNC5B to regulate angiogenesis in diabetic kidney disease

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Frontiers of Medicine 2020年第3期14卷 293-304页

作者： Xiaojing Jiao Dong Zhang Quan Hong Lei Yan Qiuxia Han Fengmin Shao guangyan cai Xiangmei Chen Hanyu Zhu Department of Nephrology Chinese People's Liberation Army(PLA)General HospitalChinese PLA Institute of NephrologyState Key Laboratory of Kidney DiseasesNational Clinical Research Center of Kidney DiseasesBeijing Key Laboratory of Kidney DiseaseBeijing 100853China Department of Nephrology Henan Provincial Key Laboratory of Kidney Disease and ImmunologyHenan Provincial People's Hospital(Zhengzhou University People's Hospital)Zhengzhou 450003China

Netrin-1,an axon guidance factor,and its receptor UNC5B play important roles in axonal development and *** study examined netrin-1 and UNC5B expression in kidneys with diabetic kidney disease (DKD) and investigated their roles in ***-1 and UNC5B were upregulated in streptozotocininduced DKD Wistar rats,and their expression was compared with that in healthy ***,exogenous netrin-1 in UNC5B-depleted human renal glomerular endothelial cells (HRGECs) inhibited cell migration and *** effect was likely associated with SRC pathway ***-1 treatment also eliminated the pro-angiogenic effects of exogenous VEGF-165 on UNC5B-silenced *** results indicate that UNC5B antagonizes netrin-1 and that UNC5B upregulation contributes partly to enhancing angiogenesis in ***,introducing exogenous netrin-1 and depleting endogenous UNC5B are potential strategies for reducing the incidence of early angiogenesis and mitigating kidney injury in DKD.

关键词： netrin-1 VEGF-165 UNC5B angiogenesis diabetic kidney disease

Blood pressure targets in patients with chronic kidney disease:Comments and controversies

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Chinese Medical Journal 2024年第3期137卷 270-272页

作者： Ying Zheng guangyan cai Xiangmei Chen Department of Nephrology First Medical Center of Chinese PLA General HospitalNational Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Disease ResearchBeijing 100853China

According to the Global Burden of Disease Study 2017,there are 132 million patients with chronic kidney disease(CKD)in China,^([1])and the prevalence of hypertension in Chinese patients with CKD(67.3%)is significantly higher than that in the general population(23.2%).^([2,3])CKD is both a cause and a consequence of hypertension,and these two conditions form a vicious cycle that leads to the high prevalence rate of hypertension in patients with *** hypertension accelerates the deterioration of renal function,which significantly increases the risk of developing end-stage renal disease(ESRD),as well as cardiovascular and cerebrovascular diseases,leading to poor patient outcomes.

关键词： patients Blood hypertension

Comparative analysis of membranous and other nephropathy subtypes and establishment of a diagnostic model

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Frontiers of Medicine 2019年第5期13卷 618-625页

作者： Hanyu Zhu Bo Fu Yong Wang Jing Gao Qiuxia Han Wenjia Geng Xiaoli Yang guangyan cai Xiangmei Chen Dong Zhang Department of Nephrology Chinese PLA General HospitalChinese PLA Institute of NephrologyState Key Laboratory of Kidney DiseasesNational Clinical Research Center of Kidney DiseasesBeijing Key Laboratory of Kidney DiseaseBeijing 100853China Department of Clinical Biochemistry Chinese PLA General HospitalBeijing 100853China Department of Nephrology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

This study aimed to compare clinical features between membranous nephropathy (MN) and nonmembranous nephropathy (non-MN), to explore the clinically difTerential diagnosis of these two types, and to establish a diagnostic model of MN. After renal biopsy was obtained, 798 patients were divided into two groups based on their examination results: primary MN group (n = 248) and non-MN group (n = 550). Their data were statistically analyzed. Logistic regression analysis indicated that anti-PLA2R antibodies, IgG, and Cr were independently correlated with MN, and these three parameters were then used to establish the MN diagnostic model. A receiver operating characteristic (ROC) curve confirmed that our diagnostic model could distinguish between patients with and without MN, and their corresponding sensitivity, specificity, and AUC were 79.9%, 89.4%, and 0.917, respectively. The cutoff value for this combination in MN diagnosis was 0.34. The established diagnostic model that combined multiple factors shows a potential for broad clinical applications in differentiating primary MN from other kidney diseases and provides reliable evidence supporting the feasibility of noninvasive diagnosis of kidney diseases.

关键词： multiparameter analysis diagnosis model membranous nephropathy

Understanding autoimmune response after SARS-CoV-2 infection and the pathogenesis/mechanisms of long COVID

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Medical Review 2024年第5期4卷 367-383页

作者： Ming Guo Shunlai Shang Mengfei Li guangyan cai Ping Li Xiangmei Chen Qinggang Li Department of Nephrology First Medical Center of Chinese PLA General HospitalState Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Diseases ResearchBeijing 100853China Department of Nephrology China-Japan Friendship HospitalBeijingChina Haihe Laboratory of Cell Ecosystem China

COVID-19 posed a major challenge to the healthcare *** and the adoption of numerous prevention and control measures enabled the gradual end of the COVID-19 ***,successive occurrence of autoimmune diseases in patients with COVID-19cannot *** COVID has been themajor focus of research due to the long duration of different symptoms and the variety of systems *** may play a crucial role in the pathogenesis of long ***,we reviewed several autoimmune disorders occurring after COVID-19 infection and the pathogenesis of long COVID.

关键词： COVID-19 SARS-CoV-2 long COVID autoimmunity

The role of transcriptional factor D-site-binding protein in circadian CCL2 gene expression in anti-Thy1 nephritis

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Cellular & Molecular Immunology 2019年第9期16卷 735-745页

作者： Yang Lu Yan Mei Lei Chen Lingling Wu Xu Wang Yingjie Zhang Bo Fu Xizhao Chen Yuansheng Xie guangyan cai Xueyuan Bai Qinggang Li Xiangmei Chen Department of Nephrology Chinese PLA General HospitalChinese PLA Institute of NephrologyState Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijingChina

Mesangial proliferative glomerulonephritis(MsPGN)is an inflammatory disease,but both the nature of disease progression and its regulation remain *** the present study,we monitored the course of anti-Thy1 nephritis from days 1 to 5 and established gene expression profiles at each time point using microarrays to explore the development of *** to the gene expression profiles,macrophage infiltration(triggered by CCL2 activation)was evident on day 1 and enhanced inflammation over the next few *** screened for genes with expression levels similar to CCL2 and found that the upregulation of the circadian gene albumin D-site-binding protein(DBP)was involved in CCL2 activation in mesangial *** importantly,CCL2 expression showed oscillatory changes similar to DBP,and DBP induced peak CCL2 expression at 16:00 a clock on day 1 in the anti-Thy1 nephritis *** knocked down DBP through transfection with a small interfering RNA(siRNA)and used RNA sequencing to identify the DBP-regulated TNF-α-CCL2 *** performed chromatin immunoprecipitation sequencing(ChIP-Seq)and the dual luciferase assay to show that DBP bound to the TRIM55 promoter,regulating gene expression and in turn controlling the TNF-α-CCL2 *** conclusion,DBP-regulated circadian CCL2 expression by the TRIM55-TNF pathway in injured mesangial cells at an early stage,which promoted macrophage recruitment and in turn triggered infiltration and inflammation in a model of anti-Thy1 nephritis.

关键词： Mesangial proliferative glomerulonephritis DBP CCL2 Trim 55 Macrophage

Single-cell RNA-Seq analysis identified kidney progenitor cells from human urine

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Protein & Cell 2021年第4期12卷 305-312页

作者： Yujia Wang Yu Zhao Zixian Zhao Dandan Li Hao Nie Yufen Sun Xiaobei Feng Ting Zhang Yu Ma Jing Nie guangyan cai Xiangmei Chen Wei Zuo East Hospital School of MedicineTongji UniversityShanghai 200092China Regend Therapeutics Co.Ltd. Zhangjiang Hi-tech ParkShanghai 201203China Ningxia Medical University Yinchuan 750004China The First Affiliated Hospital Guangzhou Medical UniversityGuangzhou 510120China Ruijin Hospital School of MedicineShanghai Jiaotong UniversityShanghai 200025China State Key Laboratory of Organ Failure Research National Clinical Research Center of Kidney DiseaseKey Laboratory of Organ Failure ResearchDivision of NephrologyNanfang HospitalSouthern Medical UniversityGuangzhou 510515China National Clinical Research Center for Kidney Diseases State Key Laboratory of Kidney DiseasesChinese PLA General HospitalBeijing 100039China

Dear Editor,Urine passes through the entire kidney and urinary tract system starting from the glomerulus and ending to the *** in the kidney and urinary tract could be exfoliated from the epithelium into the urine,while leukocyte could infiltrate from the local tissue into the urine,which makes the urine a useful subject for clinical evaluation of relevant diseases.

关键词： urine kidney urinary

Comparative risk of acute kidney injury among cancer patients treated with immune checkpoint inhibitors

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Cancer Communications 2023年第2期43卷 214-224页

作者： Fei Liu ZixianWang Xiaofan Li Zhen Zhang Yue Yang Junquan Chen Dinghua Chen Lingling Wu Xiangyu Liu Sujun Han Fangming Wang Wasilijiang Wahafu Yibo Gao Shancheng Ren Nianzeng Xing guangyan cai Xiangmei Chen Department of Urology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP.R.China Laboratory of Translational Medicine National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP.R.China Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP.R.China Department of Medical Oncology Sun Yat-sen University Cancer CenterGuangzhouGuangdongP.R.China Department of Nephrology First Medical Center of Chinese PLA General HospitalNephrology Institute of the Chinese People’s Liberation ArmyState Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Disease ResearchBeijingP.R.China Department of Plastic Surgery Plastic Surgery HospitalChinese Academy of Medical SciencesPeking Union Medical CollegeBeijingPR China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP.R.China Central Laboratory National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenGuangdongP.R.China Department of Urology Shanghai Changzheng HospitalShanghaiP.R.China

With the development and introduction of immune checkpoint inhibitors(ICIs)in cancer patients,immune-related side effects have increasingly attracted ***,the risks of immune-related renal toxicity are poorly *** this study,we performed a network meta-analysis(NMA)of ICI-related randomized clinical trials(RCTs)to elucidate the comparative risk of acute kidney injury(AKI)in cancer patients receiving different *** also sought to identify other factors potentially affecting the risk of *** and EMBASE were searched for peer-reviewed trial reports published between January 2000 and May *** studies were RCTs studying ICIs in cancer patients and reporting AKI *** performed a frequentist NMA to evaluate the risk ratios for grade 1-5 and grade 3-5 AKI between the treatment *** also assessed the absolute incidence of AKI in the ICI-containing arm using traditional direct *** significant heterogeneity was detected in a traditional direct meta-analysis,multivariable meta-regression analysis was applied to identify factors that significantly affected the absolute incidence of AKI.A total of 85 RCTs were included in this *** the NMA for the risk of grade 1-5 and 3-5 AKI,ipilimumab showed a significantly higher risk than avelumab and durvalumab,whereas 1 mg/kg nivolumab plus 3 mg/kg ipilimumab(N1I3)showed a significantly higher risk than other *** terms of treatment ranking,durvalumab±low-dose tremelimumab and avelumab were consistently among the top three safest treatments for grade 1-5 or 3-5 AKI,whereas N1I3,ipilimumab and tremelimumab were consistently among the top three treatments with the highest risk for grade 1-5 or 3-5 *** with other cancers,renal cell carcinoma and urothelial carcinoma showed a significantly higher risk of *** incidence of AKI was significantly higher with ICI+chemotherapy than with ICI *** this NMA involving largescale up-to-date ICI trials,we dem

关键词： immune checkpoint inhibitors acute kidney injury cancer immune therapy side effects

Depleting profibrotic macrophages using bioactivated in vivo assembly peptides ameliorates kidney fibrosis

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Cellular & Molecular Immunology 2024年第8期21卷 826-841页

作者： Qing Ouyang Chao Wang Tian Sang Yan Tong Jian Zhang Yulan Chen Xue Wang Lingling Wu Xu Wang Ran Liu Pu Chen Jiaona Liu Wanjun Shen Zhe Feng Li Zhang Xuefeng Sun guangyan cai Li-Li Li Xiangmei Chen Department of Nephrology First Medical Center of Chinese PLA General HospitalNephrology Institute of the Chinese People’s Liberation ArmyState Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Disease ResearchBeijing100853China Clinical Medical School Guangdong Pharmaceutical UniversityGuangzhou510006China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety National Center for Nanoscience and Technology(NCNST)Beijing100190China

Managing renal fibrosis is challenging owing to the complex cell signaling redundancy in diseased *** fibrosis involves an immune response dominated by macrophages,which activates myofibroblasts in fibrotic ***,macrophages exhibit high heterogeneity,hindering their potential as therapeutic cell ***,we aimed to eliminate specific macrophage subsets that drive the profibrotic immune response in the kidney both temporally and *** identified the major profibrotic macrophage subset(Fn1+Spp1+Arg1+)in the kidney and then constructed a 12-mer glycopeptide that was designated as bioactivated in vivo assembly PK(BIVA-PK)to deplete these ***-PK specifically binds to and is internalized by profibrotic *** inducing macrophage cell death,BIVA-PK reshaped the renal microenvironment and suppressed profibrotic immune *** robust efficacy of BIVA-PK in ameliorating renal fibrosis and preserving kidney function highlights the value of targeting macrophage subsets as a potential therapy for patients with CKD.

关键词： Renal fibrosis immune microenvironment pro-fibrotic macrophage Bioactivated in vivo assembly-PK(BIVA-PK) cell death

肾素-血管紧张素系统抑制剂在慢性肾脏病中应用的依从性与影响因素

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中华肾脏病杂志 2020年第10期36卷 812-816页

作者：张淳蔡广研解放军医学院解放军总医院第一医学中心肾脏病科国家慢性肾病临床医学研究中心肾脏疾病国家重点实验室北京市肾脏病研究重点实验室全军肾脏病研究所北京100853

循证医学研究证实肾素-血管紧张素系统(renin-angiotensin system,RAS)抑制剂能够延缓慢性肾脏病(chronic kidney disease,CKD)进展、减少心血管并发症、降低病死率,是国内外指南推荐的一线治疗药物。然而"真实世界"中各种因素影响了CK... 详细信息

循证医学研究证实肾素-血管紧张素系统(renin-angiotensin system,RAS)抑制剂能够延缓慢性肾脏病(chronic kidney disease,CKD)进展、减少心血管并发症、降低病死率,是国内外指南推荐的一线治疗药物。然而"真实世界"中各种因素影响了CKD患者RAS抑制剂应用的依从性。本文综述了RAS抑制剂在"真实世界"CKD治疗中的最新应用现状、患者用药依从性与相关影响因素,通过对目前RAS抑制剂应用存在的问题与困境的分析,提出解决方案和处理建议,指导回归正确的治疗策略,同时建议此领域需要开展基于临床实践的更多研究。

关键词：肾素-血管紧张素系统肾功能不全慢性服药依从性影响因素治疗现状