1.Prediction of different expression status of human epidermal growth factor receptor 2 in breast cancer based on multi-parameter MRI habitat imaging
Zhiheng LI ; Xiaoyan CHEN ; Xiaolei ZHANG ; Han ZHOU ; Yao FU ; Renhua WU ; Yan LIN
Chinese Journal of Radiology 2024;58(9):909-915
		                        		
		                        			
		                        			Objective:To investigate the value of multi-parameter MRI habitat imaging in differentiating human epidermal growth factor receptor 2 (HER2) expression in breast cancer.Methods:This study was cross-sectional. A retrospective analysis was conducted on the clinical and imaging data of 86 cases of primary invasive breast cancer confirmed by pathology at the Second Affiliated Hospital of Shantou University from August 2018 to July 2023. All patients were female, aged 33 to 74 (51±10) years. All patients underwent breast MRI examinations, including T 1WI, T 2WI, diffusion-weighted imaging and dynamic contrast-enhanced MRI. The fuzzy C-means clustering algorithm was applied to cluster analysis of the volume ratio of the extracellular extravascular space (V e), the rate constant (K ep), the volume transfer constant (K trans), and the apparent diffusion coefficient (ADC) for all lesions. Different habitat subregions were segmented based on breast cancer. Blood perfusion of the lesion was quantified through mean values of K trans and K ep, and cell proliferation was evaluated by the mean values of ADC and V e in each subregion. Additionally, the percentage of each subregion′s volume in relation to the total lesion volume was calculated. The Mann-Whitney U test was used to compare the differences in the volume percentages of various habitat subregions between different HER2 expression status. The diagnostic performance of statistically significant parameters in determining HER2 status was evaluated using receiver operating characteristic curves and the area under the curve (AUC). Results:Among the 86 patients with invasive breast cancer, 27 were HER2 positive and 59 were HER2 negative. Among the HER2 negative patients, 37 had low and 22 had zero HER2 expression. The volume percentages of habitat subregions 1, 2, and 3 showed statistically significant differences between HER2 positive and HER2 negative patients ( Z=2.90, P=0.004; Z=-2.04, P=0.042; Z=-2.19, P=0.029), with AUC values of 0.696, 0.638, and 0.648, respectively, for predicting HER2 positive expression. The volume percentage of habitat subregion 2 showed a statistically significant difference between low and zero HER2 expression patients ( Z=2.85, P=0.004), with an AUC value of 0.724 for predicting low versus zero HER2 expression. Conclusions:The volume percentage of habitat subregion 1 effectively distinguishes HER2 status, and the volume percentage of habitat subregion 2 effectively distinguishes between low and zero HER2 expression patients. It has significant clinical implications for identifying potential candidates for HER2-targeted therapy.
		                        		
		                        		
		                        		
		                        	
2.Analysis of the results of screening for carriers of monogenic genetic diseases in 604 couples of childbearing age
Qianyun LI ; Renhua WU ; Yuanyuan ZHANG ; Fang LIU ; Weisheng CHENG ; Jing YUAN
Acta Universitatis Medicinalis Anhui 2024;59(9):1653-1658
		                        		
		                        			
		                        			Objective To understand the carrying situation and common variation of pathogenic genes of single gene hereditary disease in childbearing age population in Anhui province,to explore the establishment of clinical application network and referral model of carrier screening in Anhui province,and to explore the application value of expansible carrier screening(expanded carrier screening,ECS)in clinic.Methods Samples were collected from 604 individuals of childbearing age,all exhibiting a normal phenotype and a family history of inherited dis-ease.These samples were obtained during the first trimester or early stages of pregnancy(≤13+6 weeks).Based on high-throughput sequencing and special PCR analysis techniques,pathogenic variants associated with 220 disea-ses were detected,and related genes were detected in the spouses of positive carriers.Results As of May 16,2023,604 tested samples had been collected,and 340 carriers of the target disease had been detected;The posi-tive rate of pathogenic variation detection was 56.29% ;A total of 499 pathogenic variants were detected,with each tested individual carrying 0-5 variants;216 cases,accounting for 35.76% ,carried a single gene recessive dis-ease pathogenic variation,which was the most common.There were 95 cases carrying two types of single gene re-cessive genetic disease pathogenic variation,accounting for 15.73% .As of now,302 couples have been reported,and a total of 7 high-risk couples have been found through screening,with a high-risk rate of 2.32% .There are a total of 5 pairs with autosomal recessive genetic pattern(both spouses carry the same pathogenic gene),and 2 pairs with X-linked genetic pattern(the female carries the X-linked pathogenic gene).Conclusion In this study,we obtained the overall carrier and clinical application of target diseases as well as the carrier rates of causative genes of common single-gene genetic diseases in 604 subjects who underwent ECS testing,which could provide scientific guidance for the establishment of a clinical application network and referral model for carrier screening in Anhui Province.
		                        		
		                        		
		                        		
		                        	
3.Role of NOD2 in dorsal root ganglion in development of neuropathic pain in rats
Renhua JU ; Chengcheng SONG ; Peng LIU ; Hua LIN ; Zhen JIA ; Jing LIANG ; Linlin ZHANG ; Keliang XIE ; Guolin WANG ; Yonghao YU
Chinese Journal of Anesthesiology 2021;41(8):984-987
		                        		
		                        			
		                        			Objective:To evaluate the role of nucleotide-binding oligomerization domain-2 (NOD2) in dorsal root ganglion in the development of neuropathic pain (NP) in rats.Methods:Thirty-two adult male SPF Sprague-Dawley rats, weighing 240-260 g, aged 2-3 months, were divided into 4 groups ( n=8 each) using a random number table method: control group (group C), NP group (group S), negative control siRAN group (group N), and NOD2-siRNA group (group R). In N and R groups, 1×10 8 IFU/ml negative control siRNA and NOD2-siRNA 10 μl were intrathecally injected, respectively, once a day for 3 consecutive days.Normal saline 10 μl was intrathecally injected once a day for 3 consecutive days in C and S groups.The model of NP was established using spared nerve injury (SNI) at 2 weeks after intrathecal injection.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before surgery and 1, 3, 7, 10, 14 and 28 days after SNI.Animals were sacrificed after measuring pain threshold on day 28, and the dorsal root ganglions (DRGs) of the lumbar segment (L 4-6) were removed for determination of the expression of NOD2 (by Western blot) and expression of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), IL-6 and NOD2 mRNA (using quantitative real-time polymerase chain reaction). Results:Compared with group C, MWT was significantly decreased at each time point after SNI, and the expression of NOD2 protein and mRNA and TNF-α, IL-1β and IL-6 mRNA in DRGs was up-regulated in group NP ( P<0.01). Compared with group NP, MWT was significantly increased at each time point after SNI, and the expression of NOD2 protein and mRNA and TNF-α, IL-1β and IL-6 mRNA in DRGs was down-regulated in group R ( P<0.01), and no significant change was found in the parameters mentioned above in group N ( P>0.05). Conclusion:The mechanism underlying the development of NP may be related to the up-regulation of NOD2 expression in DRGs, thus further promoting the expression of pro-inflammatory factors in rats.
		                        		
		                        		
		                        		
		                        	
4.Prognosis in patients underwent craniotomy for aneurysm clipping with cardiovascular diseases.
Na CHEN ; Renhua LI ; Sisi DAI ; Yanrong ZHANG ; Jun HUANG ; E WANG ; Zhenghua HE
Journal of Central South University(Medical Sciences) 2019;44(1):40-45
		                        		
		                        			
		                        			To analyze the prognostic factors for patients with or without cardiovascular diseases after craniotomy for aneurysm clipping, and to provide evidences for the improvement of perioperative management in these patients.
 Methods: We collected 297 patients who underwent craniotomy for aneurysm clipping in Xiangya Hospital of Central South University from May 2016 to February 2017. The patients were divided into two groups: the cardiovascular disease group and the non-cardiovascular disease group. The perioperative clinical data, neurological function assessments at admission and discharge and Glasgow Outcome Scale (GOS) scores of one-year-follow-up after discharge were analyzed. The primary outcome of this study was the GOS scores collected at one year after discharge. The secondary outcomes were the lengths of their ICU stay, neurological functions at discharge and adverse events morbidity during the hospitalization.
 Results: A total of 241 patients were eventually enrolled. There was no significant difference in their general data between the two groups except for their ages. The GOS scores of the one-year-follow-up were significantly different between the two groups (P=0.007). The lengths of ICU stay, neurological dysfunctions at discharge and adverse events morbidity during hospitalization were also significantly different (P=0.036, P=0.011, P=0.005, respectively). A multivariate logistic regression analysis in which GOS score was the dependent variable with age adjusted also supported the previous results that long-term prognosis was not significantly correlated with the age of patients (P>0.05), but it was correlated with cardiovascular disease and sanity at admission (P=0.001). In patients with cardiovascular diseases, there was significantly different in perioperative mortality and neurological recovery of patients who had or had not cardiovascular events (P=0.006, P=0.001, respectively).
 Conclusion: Undergoing craniotomy for aneurysm clipping, patients with cardiovascular diseases have worse outcomes in both of short and long terms. Perioperative treatments for cardiovascular disease could not only improve postoperative neurological deficits, but also reduce mortality for these patients.
		                        		
		                        		
		                        		
		                        			Craniotomy
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		                        			Humans
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		                        			Intracranial Aneurysm
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		                        			Postoperative Period
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		                        			Prognosis
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		                        			Treatment Outcome
		                        			
		                        		
		                        	
5.Prognostic roles of telomerase reverse transcriptase promoter mutation and 1p/19q co-deletion in newly-diagnosed O6-methylguanine-DNA methyltransferase promoter un-methylated/isocitrate dehydrogenase wild-type glioblastoma multiform
Qiong LU ; Xiwei ZHANG ; Yang WANG ; Xiaofang SHENG ; Xueyong WU ; Xiaobai WEI ; Hongyuan GAO ; Xiaofeng YIN ; Fang XIE ; Yueming ZHU ; Zhonghua JIN ; Zhenghua ZHANG ; Haimin WEI ; Dan LI ; Renhua HUANG ; Xianglian WANG ; Feng XIAO
Chinese Journal of Neuromedicine 2019;18(9):896-903
		                        		
		                        			
		                        			Objective To explore the prognostic values of telomerase reverse transcriptase promoter (TERTp) mutation and 1p/19q co-deletion in newly-diagnosed O6-methylguanine-DNA methyltransferase (MGMT) promoter un-methylated/isocitrate dehydrogenase (IDH) wild-type glioblastoma multiform (GBM). Methods A total of 82 patients pathologically newly-diagnosed MGMT promoter un-methylated/IDH wild-type GBM, admitted to our hospitals from March 2016 to November 2018, were included in this study. TERTp mutations (TERTp wild-type and TERTp mutation [C228 mutation and C250 mutation]) in GBM specimens were detected by PCR sequencing, 1p/19q co-deletion in GBM specimens was detected by fluorescence in situ hybridization (FISH), and clinical data, adverse reactions and prognoses of patients with different molecular typing were compared. Results There were 33 patients in the TERTp wild type group with mean age of 48 years, and 49 patients in the TERTp mutation group with mean age of 59 years; the difference of age was significant (P<0.05); there were no statistical differences in gender distribution, Karnofsky performance status (KPS) scores, tumor sites and surgical resection degrees between the two groups (P>0.05). There were 8 patients with 1p/19q co-deletion and 74 patients without 1p/19q co-deletion; no significant differences in above clinical parameters were noted between the two groups. There were no statistically significant differences in the incidences of bone marrow suppression, digestive tract response and fatigue, disease progression rate, or survival rate between patients from TERTp wild type group and TERTp mutation group, and between patients with 1p/19q co-deletion and patients without 1p/19q co-deletion (P>0.05). No significant differences in above clinical parameters, disease progression rate, and survival rate were noted between patients with C228 mutation and C250 mutation (P>0.05). Conclusion TERTp typing and 1p/19q co-deletion status do not have prognostic value in newly-diagnosed MGMT un-methylated/IDH wild-type GBM patients; patients with TERTp mutations have older age than wild-type patients; patients with C250 mutation trend to have higher survival rate than those with C228 mutation.
		                        		
		                        		
		                        		
		                        	
6.Efficacy of Decitabine Combined with Pre-Excitation Chemotherapy in the Treatment of Middle-Aged and Elderly MDS Transformed Acute Myeloid Leukemia.
Zhang-Kun LI ; Ying-Chang LAI ; Kun LI ; Ji-Xiang HE ; Yi-Rong JIANG ; Shu-Yang LIU
Journal of Experimental Hematology 2018;26(6):1713-1718
		                        		
		                        			OBJECTIVE:
		                        			To investigate the efficacy of domestic decitabine (D) combined with pre-excitation chemotherapy consisted of Ara-c, THP and G-CSF(CTG) in treatment of middle-aged and elderly patients with MDS-transformed AML and prognosis-related factors.
		                        		
		                        			METHODS:
		                        			Seventy-six patients with MDS-transformed AML treated in our hospital from June 2013 to June 2015 were selected according to treatment regimens, 76 patients were divided into 2 groups: CTG group(36 cases) and D+CTG group(40 cases). The patients in CTG group received treatment with Ara-C, THP and G-CSF; the patients received the treatment with decitabine plus CTG. The patients in 2 groups all received 4 course treatment, then received maintaining treatment. The therapeutic efficacy and incidence of adverse reactions in 2 group were compared, at the same time, the risk factors affecting the prognos of patients treated with D+CTG were analyzed.
		                        		
		                        			RESULTS:
		                        			There were no siginificant differences in age, sex, initial blood cell count, bone marrow blast ratio, disease types, chromosome karyotypes and FLT3-ITD gene mutation between 2 groups. The efficacy analysis showed that the efficacy of D+CTG was superior to CTG, ORR in D+CTG group was significantly higher than that in CTG group (72、52 vs 50%) (P<0.05), moreover, no significant differences in bone marrow inhibition digree infeetion, gastroinfestinal response and liver damage were found between 2 groups (P>0.05). The follow-np for 2 years showed that the median survival time in D+CTG group was significantly longer than that in CTG group (19.9 vs 11.0 months) (P<0.05). The multivariate analysis showed that the 1 course efficacy (RR=3.926, P=0.015) and FLT3-ITD gene mutation (RR=4.347, P=0.004) were independent risk factors affecting the efficacy of D+CTG treatment.
		                        		
		                        			CONCLUSION
		                        			The short-and long-term efficacy of domestic decitasine combined with preexcitation chenotherapy in treatment of middec-aged and eldery patients with MDS transformed AML is superior to single pre-excitation chenothrapy, moreover the incidence of adverse reactions did not increase. The 1 course efficacy and FLT-3 ITD gene mutation are the independent risk factors affecting the prognosis of patients. .
		                        		
		                        		
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Antineoplastic Combined Chemotherapy Protocols
		                        			;
		                        		
		                        			therapeutic use
		                        			;
		                        		
		                        			Decitabine
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		                        			administration & dosage
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		                        			Humans
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		                        			Leukemia, Myeloid, Acute
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		                        			drug therapy
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		                        			Middle Aged
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		                        			Myelodysplastic Syndromes
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		                        			Prognosis
		                        			
		                        		
		                        	
7.Predictors of response in patients with progressive IgA nephropathy treated with leflunomide and medium/low-dose corticosteroid
Lulin MIN ; Qin WANG ; Huihua PANG ; Minfang ZHANG ; Xiajing CHE ; Liou CAO ; Shan MOU ; Leyi GU ; Wei FANG ; Renhua LU ; Mingli ZHU ; Ling WANG ; Zanzhe YU ; Wenyan ZHOU ; Zhenyuan LI ; Jiaqi QIAN ; Zhaohui NI
Chinese Journal of Nephrology 2018;34(7):488-493
		                        		
		                        			
		                        			Objective To investigate the factors affecting the efficacy of leflunomide combined with medium/low dose corticosteroids in the treatment of progressive IgA nephropathy (IgAN).Methods Clinical and pathological parameters were collected retrospectively in patients of primary IgAN with proteinuria> 1.0 g/24 h and chronic kidney disease (CKD) stage 1-3 treated with leflunomide combined with medium/low dose corticosteroids in Ren Ji Hospital,School of Medicine,Shanghai Jiao Tong University from Jan 2005 to Dec 2010.According to the treatment effects,patients were divided into complete remission group and non-complete remission group.The biochemical and pathological indexes of the two groups were compared.Results A total of 42 patients were included.The remission rates at 3,6,9 and 12 months were 62%,64%,67% and 74%,respectively.Seventeen (40.5%) and fourteen (33.3%) patients achieved complete and partial remission after one-year treatment,and the remission rate remained stable within one year after withdrawal of drugs.The 24hour proteinuria was 1.50 (0.67,2.66) g,which was significantly reduced compared with the baseline 2.44 (1.36,3.74) g (P < 0.01).The decrease rate was 31.3%.There was a slight decrease in proteinuriawithin one year after withdrawal of drugs.Estimated glomerular filtration rate (eGFR) remained stable during the treatment and a year of follow-up.No serious adverse event was observed during the followup period.Among 31 responder patients,6(19.4%) patients relapsed.Logistic multivariate regression analysis suggested that the degree of renal interstitial inflammatory infiltration was an independent predictor of complete remission with one-year treatment of leflunomide combined with medium / low dose corticosteroids (HR=0.067,95% CI 0.008-0.535,P=0.011).Conclusions IgAN treated with leflunomide and medium/low dose corticosteroids can achieve remission in early stage,and the remission rate remains stable after withdrawal of drugs.It is a safe option for the treatment of IgAN.Renal interstitial inflammatory infiltration is an independent predictor of complete remission.
		                        		
		                        		
		                        		
		                        	
8.Mechanism of microRNA150 in regulating invasion and metastasis of gastric cancer by targeting Ras-interacting protein 1
Yin NI ; Jinli ZHANG ; Renhua SUN
Chinese Journal of Digestion 2017;37(5):319-325
		                        		
		                        			
		                        			Objective To investigate the effects and mechanism of microRNA150 (miRNA150) on proliferation, invasion and metastasis of gastric cancer.Methods From January 2015 to June 2016, 45 surgical specimens were collected.The expression of miRNA150 and Ras-interacting protein 1(RASIP1) at miRNA level in gastric cancer tissues and paracancerous tissues were quantified by quantitative real-time fluorescent reverse transcriptase-polymerase chain reaction (qRT-PCR).The correlation between miRNA150 and the biological features of gastric cancer as well as RASIP1 expression was analyzed.Gastric cancer cell line SGC-7901 was cultured and transfected with pcDNA3.1-miRNA150 expression plasmids.The effect of miRNA150 over-expression on the proliferation of SGC-7901 cells was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-dipheayl 2-H-tetrazolium bromide (MTT) assay.And the effect of miRNA150 over-expression on the invasion and metastasis of SGC-7901 cells was detected by Transwell assay.The potential target gene of miRNA150 was analyzed by bioinformatics software and dual-luciferase reporter assay system.The effect of miRNA150 over-expression on RASIP1 expression in SGC-7901 cells was tested by qRT-PCR and Western blotting.Analysis of variance and t test were used to compare normal distribution data.And the Mann-Whitney rank sum test was used to compare skewed distribution data.Spearman assay was used for correlation analysis.Results The median level of miRNA150 in gastric cancer tissue was higher than that of paracancerous tissues (3.85, 0.26 to 7.92 vs 1.98, 0.19 to 5.66), and the difference was statistically significant (U=466.22,P<0.05).The median level of RASIP1 mRNA in gastric cancer tissue (1.65, 0.13 to 3.59) was lower than that of paracancerous tissues (2.96, 0.59 to 6.08), and the difference was statistically significant (U=522.31,P<0.05).The results of correlation analysis indicated that RASIP1 expression level was negatively correlated with miRNA150 expression (r=-0.589, P=0.008).The RASIP1 expression at mRNA level was negatively correlated with miRNA150 expression (r=-0.614, P=0.004).The dual-luciferase reporter assay showed RASIP1 was the target gene of miRNA150.The miRNA150 expression level was related with tumor size, TNM staging and lymph node metastasis(χ2=5.81, 6.00 and 10.04,all P<0.05).The results of MTT assay showed that after SGC-7901 cells cultured for 24 hours, the A value of pcDNA3.1-miRNA150 plasmid transfected cells was higher than that of the untransfected SGC-7901 cells (0.51±0.04 vs 0.79±0.03), and the difference was statistically significant (t=4.745, P<0.05).The results of Transwell assay indicated that there were more invasive and metastatic cells in pcDNA3.1-miRNA150 plasmid transfected cells.The results of qRT-PCR showed that the relative levels of RASIP1 mRNA in control group, pcDNA3.1-miRNA150 plasmid transfected cells and pcDNA3.1 empty plasmid transfected cells were 1.00±0.02, 0.51±0.03 and 1.08±0.03, respectively.The RASIP1 mRNA level in pcDNA3.1-miRNA150 plasmid transfected cells was lower than untransfected and pcDNA3.1 empty plasmid transfected cells, and the differences were statistically significant (t=3.940, 4.120, both P<0.05).miRNA150 could negtively regulate the RASIP1 protein expression and promote the proliferation and invasion of gastric cacer cells.Conclusions Over-expression of miRNA150 induced invasion and metastasis of gastric cancer by down-regulating RASIP1 expression.miRNA150 may be a novel biomarker for the diagnosis and treatment of tumor metastasis.
		                        		
		                        		
		                        		
		                        	
9."Performance appraisal for rational drug use against ""Separation of clinic from pharmacy"" reform:experiment and practice"
Chinese Journal of Hospital Administration 2017;33(4):300-302
		                        		
		                        			
		                        			The paper presented the scheme of performance appraisal on rational administration of drugs and its outcomes against the background of separation of clinic from pharmacy reform.It found the proportion of medicine decreasing year by year;pass rate of prescriptions above 99%;drug cost per visit decreasing significantly;and the usage rate of antibiotics up to the national standards in a rational trend.Rational drug use has become an effective tool in overseeing physicians' rational drug use and ensuring patient safety.
		                        		
		                        		
		                        		
		                        	
10.Renji acute kidney injury score is a useful tool to predict acute kidney injury after cardiac surgery
Shang LIU ; Leyi GU ; Yucheng YAN ; Miaolin CHE ; Bo XIE ; Song XUE ; Mingli ZHU ; Renhua LU ; Hong CAI ; Weiming ZHANG ; Zhaohui NI ; Jiaqi QIAN
Chinese Journal of Nephrology 2017;33(3):161-168
		                        		
		                        			
		                        			Objective To validate the effect of Renji acute kidney injury score (RAKIS) on predicting patients with acute kidney injury (AKI) after cardiac surgeries,and make comparison with Cleveland score,simplified renal index (SRI) and acute kidney injury following cardiac surgery (AKICS).Methods Patients undergoing open heart surgery from 2008/01/01 to 2010/10/31 in Renji hospital were enrolled,and their scores of those four scoring models were calculated.AKI patients were diagnosed by KDIGO,and those scores of AKI patients and non-AKI patients were compared.Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to decide the predictive values of those models.Results A total of 1126 patients were chosen in this cohort,with the average age of (58.43±14.88) years (rang from 18 to 88).The male to female ratio was 1.47:1.And 355(31.5%) patients were developed AKI.AKI stage Ⅰ,Ⅱ and Ⅲ were 65.4%,23.7% and 11.0% respectively.RAKIS was significantly higher in AKI patients than in non-AKI patients (17.5 vs 9.0,P < 0.001).The AUCs of RAKIS to predict AKI,AKI Ⅱ-Ⅲ stages,renal replacement therapy (RRT)and in-hospital death were 0.818,0.819,0.800 and 0.784 respectively.The AUCs of Cleveland score and SRI were 0.659 to 0.710,lower than those of RAKIS and AKICS.AKICS had lower value for predicting AKI and AKI Ⅱ-Ⅲ stages (AUC 0.766 and 0.793),but good value in predicting RRT and inhospital death after surgery (AUC 0.804 and 0.835) as compared with RAKIS.Conclusions RAKIS is valid and accurate in the discrimination of KDIGO defined AKI patients,while for predicting the composite end point,AKICS may be more useful.
		                        		
		                        		
		                        		
		                        	
            

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