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Eff ects of continuous renal replacement therapy on infl ammation-related anemia, iron metabolism and prognosis in sepsis patients with acute kidney injury

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World Journal of Emergency Medicine 2023年第3期14卷 186-192页

作者： Meng-meng An Chen-xi Liu Ping Gong Intensive Care Unit the Affi liated Dalian Friendship Hospital of Dalian Medical UniversityDalian 116100China Department of Emergency Medicine the First Affi liated Hospital of Dalian Medical UniversityDalian 116011China Department of Emergency Medicine Shenzhen People's Hospital(the Second Clinical Medical College of Jinan Universitythe First Affi liated Hospital of Southern University of Science and Technology)Shenzhen 518020China

BACKGROUND:This study aims to evaluate the eff ect of continuous renal replacement therapy(CRRT)on inflammation-related anemia,iron metabolism,and the prognosis in sepsis patients with acute kidney injury(AKI).METHODS:Sepsis patients with AKI were prospectively enrolled and randomized into the CRRT and control *** clinical and laboratory data on days 1,3 and 7 after intensive care unit(ICU)admission were *** serum interleukin(IL)-6,hepcidin,erythropoietin,ferritin,and soluble transferrin receptor(sTfR)were determined by enzyme-linked immunosorbent *** Sequential Organ Failure Assessment(SOFA)score and 28-day mortality were *** were analyzed using Pearson’s Chi-square test or Fisher’s exact test(categorical variables),and Mann-Whitney U-test or t-test(continuous variables).RESULTS:The hemoglobin and serum erythropoietin levels did not signifi cantly diff er between the CRRT and control groups though gradually decreased within the first week of ICU *** days 3 and 7,the serum IL-6,hepcidin,ferritin,and red blood cell distribution width significantly decreased in the CRRT group compared to the control group(all P<0.05).On day 7,the serum iron was significantly elevated in the CRRT group compared to the control group(P<0.05).However,the serum sTfR did not signifi cantly diff er between the groups over *** addition,the SOFA scores were signifi cantly lower in the CRRT group compared to the control group on day *** 28-day mortality did not signifi cantly diff er between the control and CRRT groups(38.0%vs.28.2%,P=0.332).CONCLUSION:CRRT might have beneficial effects on the improvement in inflammationrelated iron metabolism and disease severity during the fi rst week of ICU admission but not anemia and 28-day mortality in sepsis patients with AKI.

关键词： Sepsis Continuous renal replacement therapy acute kidney injury Anemia Iron metabolism

Passively-targeted mitochondrial tungsten-based nanodots for efficient acute kidney injury treatment

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Bioactive Materials 2023年第3期21卷 381-393页

作者： Qiong Huang Yuqi Yang Tianjiao Zhao Qiaohui Chen Min Liu Shuting Ji Yan Zhu Yunrong Yang Jinping Zhang Haixin Zhao Yayun Nan Kelong Ai Department of Pharmacy Xiangya HospitalCentral South UniversityChangsha410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha410008China Xiangya School of Pharmaceutical Sciences Central South UniversityChangsha410078China Hunan Provincial Key Laboratory of Cardiovascular Research Xiangya School of Pharmaceutical SciencesCentral South UniversityChangsha410078China Geriatric Medical Center People’s Hospital of Ningxia Hui Autonomous RegionYinchuan750002China

acute kidney injury(AKI)can lead to loss of kidney function and a substantial increase in *** burst of reactive oxygen species(ROS)plays a key role in the pathological progression of ***-targeted antioxidant therapy is very promising because mitochondria are the main source of ROS in *** nanodrugs with actively targeted mitochondria have achieved encouraging success in many oxidative stress-induced ***,most strategies to actively target mitochondria make the size of nanodrugs too large to pass through the glomerular system to reach the renal tubules,the main damage site of ***,an ultra-small Tungsten-based nanodots(TWNDs)with strong ROS scavenging can be very effective for treatment of *** can reach the tubular site after crossing the glomerular barrier,and enter the mitochondria of the renal tubule without resorting to complex active targeting *** our knowledge,this is the first time that ultra-small negatively charged nanodots can be used to passively target mitochondrial therapy for *** in-depth study of the therapeutic mechanism,such passive mitochondria-targeted TWNDs are highly effective in protecting mitochondria by reducing mitochondrial ROS and increasing *** addition,TWNDs can also reduce the infiltration of inflammatory *** work provides a new way to passively target mitochondria for AKI,and give inspiration for the treatment of many major diseases closely related to mitochondria,such as myocardial infarction and cerebral infarction.

关键词： ROS-scavenging Anti-inflammatory acute kidney injury Passively-targeted mitochondrial Tungsten-Based Nanodots

Protective mechanisms of Leontopodium leontopodioides extracts on lipopolysaccharide-induced acute kidney injury via the NF-κB/NLRP3 pathway

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Chinese Journal of Natural Medicines 2023年第1期21卷 47-57页

作者： BAI Xue MA Qianqian LI Qi YIN Meizhen XIN Ying ZHEN Dong WEI Chengxi Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System Inner Mongolia Minzu UniversityTongliao 028000China College of Preventive Medicine Medical CollegeInner Mongolia Minzu UniversityTongliao 028000China Institute of Pharmaceutical Chemistry and Pharmacology Inner Mongolia Minzu UniversityTongliao 028000China College of Traditional Mongolian Medicine Inner Mongolia Minzu UniversityTongliao 028000China

Sepsis-induced uncontrolled systemic inflammatory response syndrome(SIRS)is a critical cause of multiple organ *** kidney injury(AKI)is one of the most serious complications associated with an extremely high mortality rate in SIRS,and it lacked simple,safe,and effective treatment *** leontopodioides(Willd.)Beauv(LLB)is commonly used in traditional Chinese medicine for the treatment of acute and chronic ***,it remains unclear whether lipopolysaccharide(LPS)affects LPS-induced *** identify the molecular mechanisms of LLB in LPS-induced HK-2 cells and mice,LLB was prepared by extraction with 70%methanol,while a lipopolysaccharide(LPS)-induced HK-2 cell model and an AKI model were established in this *** histopathology staining was performed to observe the morphology *** cell supernatant and kidney tissues were collected for determining the levels of inflammatory factors and protein expression by ELISA,immunofluorescence,and Western *** results indicated that LLB significantly reduced the expression of IL-6 and TNF-αin LPS-induced HK-2 cells,as well as the secretion of IL-6,TNF-α,and IL-1βin the *** same results were observed in LPS-induced AKI *** studies revealed that LLB remarkably improved oxidative stress and apoptosis based on the content of MDA,SOD,and CAT in serum and TUNEL staining ***,LLB significantly reduced the mortality due to LPS *** histopathology staining results supported these ***,immunofluorescence and Western blot results confirmed that LLB significantly reduced the expression of the protein related to the NF-κB signaling pathway and NLRP3,ASC,and Caspase-1 which were significantly increased through LPS *** findings clearly demonstrated the potential use of LLB in the treatment of AKI and the crucial role of the NF-κB/NLRP3 pathway in the process through which LLB attenuates AKI induced by LPS.

关键词： Leontopodium leontopodioides acute kidney injury Ethnopharmacology

Protective Mechanism of Cordyceps sinensis Treatment on acute kidney injury-Induced acute Lung injury through AMPK/mTOR Signaling Pathway

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中国结合医学杂志:英文版 2023年第10期29卷 875-884页

作者： WANG Ruo-lin LIU Shu-hua SHEN Si-heng JIAN Lu-yong YUAN Qi GUO Hua-hui HUANG Jia-sheng CHEN Peng-hui HUANG Ren-fa Nephropathy Department Shenzhen Hospital(Futian)of Guangzhou University of Chinese MedicineShenzhenGuangdong Province518034China The Third Clinical Medical School Guangzhou University of Chinese MedicineGuangzhou510006China

Objective: To investigate protective effect of Cordyceps sinensis(CS) through autophagyassociated adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) signaling pathway in acute kidney injury(AKI)-induced acute lung injury(ALI). Methods: Forty-eight male Sprague-Dawley rats were divided into 4 groups according to a random number table, including the normal saline(NS)-treated sham group(sham group), NS-treated ischemia reperfusion injury(IRI) group(IRI group), and low-(5 g/kg·d) and high-dose(10 g/kg·d) CS-treated IRI groups(CS1 and CS2 groups), 12 rats in each group. Nephrectomy of the right kidney was performed on the IRI rat model that was subjected to 60 min of left renal pedicle occlusion followed by 12, 24, 48, and 72 h of reperfusion. The wet-to-dry(W/D) ratio of lung, levels of serum creatinine(Scr), blood urea nitrogen(BUN), inflammatory cytokines such as interleukin-βand tumor necrosis factor-α, and biomarkers of oxidative stress such as superoxide dismutase, malonaldehyde(MDA) and myeloperoxidase(MPO), were assayed. Histological examinations were conducted to determine damage of tissues in the kidney and lung. The protein expressions of light chain 3 Ⅱ/light chain 3 Ⅰ(LC3-Ⅱ/LC3-Ⅰ), uncoordinated-51-like kinase 1(ULK1), P62, AMPK and mTOR were measured by Western blot and immunohistochemistry, respectively. Results: The renal IRI induced pulmonary injury following AKI,resulting in significant increases in W/D ratio of lung, and the levels of Scr, BUN, inflammatory cytokines, MDA and MPO(Pinjury following renal IRI through activation of the autophagy-related AMPK/mTOR signaling pathway in AKI-i

关键词： autophagy ischemic reperfusion injury acute kidney injury acute lung injury Cordyceps sinensis Chinese medicine

Development and validation of a nomogram for predicting overall survival in cirrhotic patients with acute kidney injury

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World Journal of Gastroenterology 2022年第30期28卷 4133-4151页

作者： Yi-Peng Wan An-Jiang Wang Wang Zhang Hang Zhang Gen-Hua Peng Xuan Zhu Department of Gastroenterology and Hepatology The First Affiliated Hospital of Nanchang UniversityNanchang 331706Jiangxi ProvinceChina Biomolecular Research Laboratory Jiangxi Clinical Research Center for GastroenterologyNanchang 331706Jiangxi ProvinceChina

BACKGROUND acute kidney injury(AKI)is a common and severe complication in patients with cirrhosis,and is associated with poor ***,identifying cirrhotic patients with AKI who are at high risk of mortality is very important and may be helpful for providing timely medical interventions to improve the prognosis of these ***,studies focused on investigating the risk factors for the mortality of cirrhotic patients with AKI were *** To identify risk factors for mortality and establish a nomogram for predicting the prognosis of these *** Two hundred fifty consecutive patients with cirrhosis and AKI were recruited and randomly divided into training cohort(n=173)and validation cohort(n=77).In the training cohort,potential risk factors for death were identified by performing a Cox regression analysis,and a nomogram was *** predictive performance of the nomogram was internally and externally validated by calculating the area under the receiver operating characteristic curve(AUROC),constructing a calibration curve and performing decision curve *** The serum sodium level,international normalized ratio,peak serum creatinine level>1.5 mg/dL,the presence of hepatic encephalopathy and diabetes were potential risk factors for mortality of cirrhotic patients with AKI in the training dataset.A prognostic nomogram incorporating these variables was established for predicting the overall survival of these *** with Child-Turcotte-Pugh,the model for end-stage liver disease(MELD)and the MELD-Na scores,the nomogram in predicting 90-and 180-d mortality exhibited better discriminatory power with AUROCs of 0.792 and 0.801 for the training dataset and 0.817 and 0.862 for the validation dataset,*** a nomogram score of 98,patients were divided into low-and high-risk groups,and high-risk patients had a higher mortality *** A prognostic nomogram displayed good performance for predicting th

关键词： acute kidney injury Cirrhosis Nomogram Prognosis

Ticagrelor Protects against Sepsis-Induced acute kidney injury through an Adenosine Receptor-Dependent Pathway

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Current Medical Science 2022年第3期42卷 505-512页

作者： Yu-han CAO Qian-cheng XU Yu-wei WANG Yang LING Cong FU Department of Nephrology Yi Ji Shan Hospital affiliated to Wan Nan Medical CollegeWuhu 241000China Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution Wan Nan Medical CollegeWuhu 241000China Department of Critical Care Medicine Yi Ji Shan Hospital affiliated to Wan Nan Medical CollegeWuhu 241000China Department of Cardiology Yi Ji Shan Hospital Affiliated to Wan Nan Medical CollegeWuhu 241000China

Objective Ticagrelor is a widely used anti-platelet ***,the mechanisms by which ticagrelor protects against sepsis-induced acute kidney injury(AKI)have not been clearly *** designed this study to explore the protective effect of ticagrelor on sepsis-induced AKI and to explore the underlying *** C57BL6J mice received oral ticagrelor(20 mg/kg and 50 mg/kg)for 7 days,and then caecal ligation and puncture(CLP)were *** adenosine receptor antagonist,CGS15943,was administered(10 mg/kg,intraperitoneal injection)to block the adenosine pathway 2 h before *** 24 h,serum creatinine levels were *** acid-Schiff(PAS)staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)staining were employed to analyze pathological changes and cell *** concentrations of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and mRNA expression of tissue TNF-αand IL-1βwere *** blotting analysis was used to determine AKT and mammalian target of rapamycin(mTOR)protein expression in the *** PAS staining showed less swelling of renal tubules,and TUNEL staining revealed less cell apoptosis in the ticagrelor group than in the CLP *** creatinine levels were significantly lower in the ticagrelor group than in the CLP ***,significantly lower serum and kidney levels of TNF-αand IL-1βwere observed in the ticagrelor ***15943 blocked the effects of *** blotting analysis showed increased phosphorylation of AKT and mTOR in the kidneys of the 50 mg/kg ticagrelor *** adenosine receptor antagonist inhibited the activation of AKT and *** This study demonstrates that the protective effect of ticagrelor on sepsis-induced AKI depends on adenosine receptor activation and the subsequent increase of AKT and mTOR phosphorylation.

关键词： sepsis acute kidney injury adenosine phosphatidyl-inositol 3-kinase mammalian target of rapamycin

TOPK Activation Exerts Protective Effects on Cisplatin-induced acute kidney injury

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Current Medical Science 2022年第4期42卷 742-753页

作者： Hui ZHANG Qing-qing DONG Hua-pan SHU Yu-chi TU Qian-qian LIAO Li-jun YAO Department of Nephrology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China

Objective:T-LAK-cell-originated protein kinase(TOPK),a PSD95-Disc large-ZO1(PDZ)binding kinase(PBK),is a novel member of the mitogen-activated protein kinase(MAPK)*** have shown that TOPK plays a critical role in the function of tumor cells,including apoptosis and ***,little is known on the effect of TOPK in cisplatin-induced acute kidney injury(CP-AKI).This study aimed to investigate the role and mechanism of TOPK in ***:Cisplatin was administered to C57BL/6 mice and cultured kidney tubular epithelial cells(TECs)to establish the CP-AKI murine or cellular *** were then stimulated with the specific inhibitor of TOPK OTS514 or transfected with the recombinant-activated plasmid TOPK-T9E to inhibit or activate *** TECs were treated with AKT inhibitorⅧfollowing stimulation with OTS514 or *** blotting and flow cytometry were used to evaluate the cell cycle and apoptosis of ***:The analysis revealed that the TOPK activity was significantly suppressed by cisplatin,both in vivo and in ***,the pharmacological inhibition of TOPK by OTS514,a specific inhibitor of TOPK,exacerbated the cisplatin-induced cell cycle arrest in the G2/M phase and apoptosis of cultured ***,the TOPK activation via the TOPK-T9E plasmid transfection could partially reverse the cell cycle arrest at the G2/M phase and apoptosis of cisplatin-treated *** addition,AKT/protein kinase B(PKB),as a TOPK target protein,was inhibited by cisplatin in cultured *** pharmaceutical inhibition of AKT further aggravated the apoptosis of TECs induced by cisplatin or TOPK *** systematically mediated the apoptosis via the AKT pathway in the CP-AKI cell ***:These results indicate that TOPK activation protects against CP-AKI by ameliorating the G2/M cell cycle arrest and cell apoptosis.

关键词： acute kidney injury cisplatin cell cycle apoptosis T-LAK-cell-originated protein kinase/PSD95-Disc large-ZO1 binding kinase

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

Intraoperative Blood Glucose Levels and Postoperative acute kidney injury in Pediatric Patients Having Congenital Heart Surgery under Cardiopulmonary Bypass

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Congenital Heart Disease 2023年第4期18卷 475-488页

作者： Dongyun Bie Hongbai Wang Chaobin Zhang Chunrong Wang Yuan Jia Su Yuan Sheng Shi Jiangshan Huang Jianhui Wang Fuxia Yan Department of Anesthesiology Fuwai HospitalNational Centre for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Anesthesiology Fuwai HospitalChinese Academy of Medical SciencesShenzhenChina Department of Anesthesiology Peking Union Medical College HospitalBeijingChina

Purpose:This study sought to explore the effect of intraoperative mean blood glucose levels and variability on postoperative acute kidney injury(AKI)in children undergoing congenital cardiac ***:We conducted a prospective nested case-control study in children(age<18 years)undergoing congenital heart surgery with cardiopulmonary bypass(CPB)at the Fuwai Hospital between April 01,2022 and July 30,*** were individuals who developed AKI within the first postoperative 7 days(AKI group)and controls were those without AKI(Non-AKI group)according to KDIGO *** and Non-AKI groups unmatched and 1:1 matched by age,sex,and baseline serum creatinine were separately *** logistic and conditional logistic regressions were used to assess the associations between blood glucose variables and ***:688 consecutively approached patients were included in the final *** multivariate analysis,intra-CPB(adjusted odds ratio[OR]0.802;95%confidence interval[CI],0.706 to 0.912;p=0.001)and post-CPB(adjusted OR 0.830;95%CI,0.744 to 0.925;p=0.001)blood glucose levels were associated with postoperative *** were no significant differences in pre-CPB blood glucose(adjusted OR 0.926;95%CI,0.759 to 1.129;p=0.446)or intraoperative glycemic fluctuations(adjusted OR 0.905;95%CI,0.723 to 1.132;p=0.382)between AKI and Non-AKI *** based on matched cases and controls were consistent with those from the unmatched ***:Higher intraoperative blood glucose levels during and after CPB were protective factors against postoperative AKI in pediatric patients after congenital heart surgery.

关键词： Blood glucose children congenital heart surgery cardiopulmonary bypass acute kidney injury