ObjectiveTo explore the effect of serum containing Zhenwutang on myocardial mast cell apoptosis induced by angiotensin Ⅱ （AngⅡ） and the mechanism of the correlation between apoptosis and mitochondrial autophagy. MethodsIn this experiment， AngⅡ and serum containing Zhenwutang with different concentrations were used to interfere with H9C2 cardiomyocytes for 24 h， and the survival rate of H9C2 cardiomyocytes was detected by cell counting kit-8 （CCK-8） to screen the optimal concentration for the experiment. Enzyme-linked immunosorbent assay （ELISA） was used to detect the content of B-type natriuretic peptide （BNP） in cell culture supernatant， and immunofluorescence was used to detect the cell surface area to verify the construction of the myocardial mast cell model. Subsequently， the experiment was divided into a blank group （20% blank serum）， a model group （20% blank serum + 5×10^-5 mol·L^-1 AngⅡ）， low-， medium-， and high-dose （5%， 10% and 20%） serum containing Zhenwutang groups， an autophagy inhibitor group （1×10^-4 mol·L^-1 3-MA）， and autophagy inducer group （1×10^-7 mol·L^-1 rapamycin）. The apoptosis level of H9C2 cells and the changes of mitochondrial membrane potential were detected by flow cytometry. The lysosomal probe （Lyso Tracker） and mitochondrial probe （Mito Tracker） co-localization was employed to detect autophagy. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect Caspase-3， Caspase-9， B-cell lymphoma 2 （Bcl-2）， Bcl-2-related X protein （Bax）， and cytochrome C （Cyt C） in apoptosis-related pathways and the relative mRNA expression of ubiquitin ligase （Parkin）， phosphatase and tensin homolog （PTEN）-induced kinase 1 （PINK1）， and p62 protein in mitochondrial autophagy-related pathways. Western blot was used to detect cleaved Caspase-3， cleaved Caspase-9， Bax， Bcl-2， and Cyt C in apoptosis-related pathways， phosphorylated ubiquitin ligase （p-Parkin）， phosphorylated PTEN-induced kinase 1 （p-PINK1）， p62， and Bcl-2 homology domain protein Beclin1 in mitochondrial autophagy-related pathways， and the change of microtubule-associated protein 1 light chain 3 （LC3） Ⅱ/Ⅰ ratio. ResultsCCK-8 showed that when the concentration of AngⅡ was 5×10^-5 mol·L^-1， the cell activity was the lowest， and there was no cytotoxicity. At this concentration， the surface area of cardiomyocytes was significantly increased （P<0.01）， and the content of BNP in the supernatant of culture medium was significantly increased （P<0.05）. Therefore， AngⅡ with a concentration of 5×10^-5 mol·L^-1 was selected for the subsequent modeling of myocardial mast cells. Compared with the blank group， the model group and the autophagy inhibitor 3-MA group had a significantly increased apoptosis rate （P<0.01） and significantly decreased mitochondrial membrane potential （P<0.01）. The results of immunofluorescence co-localization showed that compared with the blank group， the model group had a significantly decreased number of red and green fluorescence spots. The results of Real-time PCR showed that compared with that in the blank group， the relative mRNA expression of Bax， Caspase-3， Caspase-9， Cyt C， and p62 in the model group was significantly up-regulated （P<0.01）， while the relative mRNA expression of Bcl-2， Parkin， and PINK1 was significantly down-regulated （P<0.01）. In addition， the relative protein expression of Bax， cleaved Caspase-3， cleaved Caspase-9， Cyt C， and p62 was significantly up-regulated （P<0.01）. The LC3Ⅱ/Ⅰ was significantly decreased， and the relative protein expression of Bcl-2， p-Parkin， p-PINK1， and Beclin1 was significantly down-regulated （P<0.01）. Compared with the model group， the serum containing Zhenwutang groups and the autophagy inducer group had significantly decreased apoptosis rate （P<0.01）， and the decrease ratio of mitochondrial membrane potential is significantly lowered （P<0.01） in a dose-dependent manner. Additionally， both red and green fluorescence spots became more in these groups. In the 3-MA group， the number of red and green fluorescence spots decreased significantly. The relative mRNA expression of Bax， Caspase-3， Caspase-9， Cyt C， and p62 was significantly down-regulated （P<0.05， P<0.01）， while that of Bcl-2， Parkin， and PINK1 was significantly up-regulated （P<0.01）. In the serum containing Zhenwutang groups， the relative protein expression levels of Bax， cleaved Caspase-3， cleaved Caspase-9， Cyt C， and p62 were significantly down-regulated （P<0.05，P<0.01）. The LC3Ⅱ/Ⅰ was significantly increased， and the relative protein expression levels of Bcl-2， p-Parkin， p-PINK1， and Beclin1 were significantly up-regulated （P<0.01）. ConclusionThe serum containing Zhenwutang can reduce the apoptosis of myocardial mast cells and increase mitochondrial autophagy. This is related to the inhibition of intracellular Bax/Bcl-2/Caspase-3 apoptosis pathway and regulation of Parkin/PINK1 mitochondrial autophagy pathway.

OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

Objective To explore the changes in early serum calcium,serum phosphorus,and calcium-phosphorus product levels in patients with fractures and analyze their correlation with the fracture site.Methods 1 049 patients with fractures admitted to Sichuan Province Orthopedic Hospital from January 2021 to November 2023 were selected as the research subjects.According to the fracture location,they were roughly divided into two groups:upper body fracture(n=478)and lower body fracture(n=571).Carefully divided into ten groups:vertebral fracture(n=108),clavicle fracture(n=109),upper limb fracture(n=106),hand fracture(n=104),femoral neck fracture(n=103),femoral intertrochanteric fracture(n=106),patella fracture(n=101),lower limb fracture(n=103),foot fracture(n=105)and other fractures(n=104).Another 110 cases of healthy physical examination people during the same period were selected as the control group.Venous blood was drawn from all patients twice on the day of emergency within 24 to 48 hours after admission,serum calcium and serum phosphorus were measured,and the calcium-phosphorus product was calculated.Compare the changes in the levels of the three and analyzed their correlation with the fracture site.Results Compared with the control group,the serum calcium(2.27±0.12 mmol/L,2.19±0.12 mmol/L vs 2.35±0.10mmol/L),serum phosphorus(1.00±0.20mmol/L,1.08±0.19mmol/L vs 1.15±0.15mmol/L),and calcium-phosphorus product(28.10±6.00mg/dl,29.30±5.85mg/dl vs 33.41±4.87mg/dl)of fracture patients were all reduced on the day of emergency and 24 to 48 hours after admission,and the differences were statistically significant(t=6.804,12.501;7.475,3.722;8.964,7.115,all P＜0.01).Comparing upper and lower body fractures,serum calcium,serum phosphorus,and calcium-phosphorus product on the emergency day was lower in lower body fracture than in upper body fracture(t=4.129,5.931,6.660,all P＜0.01),24 to 48 hours after admission,only the serum calcium and calcium-phosphorus product were lower in lower body fracture than in upper body fracture(t=6.432,1.990,all P＜0.05),and the differences were statistically significant,respectively.Comparing along the time axis,24 to 48 hours after admission compared with the emergency day,both upper and lower body fractures showed a decrease in serum calcium and an increase in serum phosphorus(t=12.779,-5.730;16.919,-14.358),calcium-phosphorus product only increased in lower body fracture(t=-8.860),and the differences were statistically significant(all P＜0.01),respectively.Compared with the day of emergency,24 to 48 hours after admission for patients with fractures in different parts,except for vertebral fracture,serum calcium in the other nine groups decreased(t=6.233～11.349,all P＜0.01),except for upper limb fracture and hand fracture,the serum phosphorus in the other eight groups increased(t=-7.770～-3.327,all P＜0.01),the calcium-phosphorus product of vertebral fracture,femoral neck fracture,femoral intertrochanteric fracture,lower limb fracture,foot fracture,and other fractures increased(t=-5.819～-2.927,all P＜0.01),and the differences were statistically significant,respectively.Conclusion The serum calcium,serum phosphorus,and calcium-phosphorus product of patients with fractures all decreased on the day of emergency.24 to 48 hours later,the serum calcium of most patients continued to decrease while the serum phosphorus and calcium-phosphorus product gradually increased.The degree of change in their levels was related to the fracture site.

The quality of moxa is a key factor affecting the efficacy of moxibustion. Traditional moxa grades are evaluated by the leaf-to-moxa ratio, but there is a lack of support from scientific data. Scanning electron microscopy(SEM), Image Pro Plus, Van Soest method, and stimultaneous thermal analysis(TGA/DSC) were used to characterize the scientific implication of the combustion differences between moxa with different leaf-to-moxa ratios(processed by crusher). The results showed that the median lengths from non-secretory trichomes(NSTs) of natural NSTs and moxa with leaf-to-moxa ratios of 3∶1, 5∶1, 10∶1, and 15∶1 were 542.46, 303.24, 291.18, 220.69, and 170.61 μm, respectively. The cellulose content of moxa increased significantly(P<0.05) with the increase in leaf-to-moxa ratio and the combustion parameters(T_i, t_i, D_i, C,-R_p,-R_v, S, D_b, and J_(total)) all showed an increasing trend. The correlation results showed that the burning properties of moxa(T_i,-R_v, t_i, and J_2) were significantly and positively correlated with cellulose content. NSTs with a length of 1-200 μm were significantly and positively correlated with J_2. NSTs with a length of 200-600 μm were significantly and positively correlated with J_1, T_(peak2), T_(peak1), and-R_v, and negatively correlated with J_(total), T_b, and t_b. As the leaf-to-moxa ratio increases, the NSTs in the moxa become shorter and the cellulose content increases, which is more conducive to ignition performance, heat release, and a milder, longer-lasting burn. The "NSTs-cellulose-TGA/DSC" quantitative evaluation method scientifically reveals the scientific connotation of the combustion of moxa with different leaf-to-moxa ratios and provides a scientific basis for the establishment of quality evaluation methods for moxa with different leaf-to-moxa ratios.
Trichomes ; Moxibustion ; Hot Temperature ; Plant Leaves

DMRT, a gene family related to sexual determination, encodes a large group of transcription factors (DMRTs) with the double-sex and mab-3 (DM) domain (except for DMRT8), which is able to bind to and regulate DNAs. Current studies have shown that the DMRT gene family plays a critical role in the development of sexual organs (such as gender differentiation, gonadal development, germ cell development, etc.) as well as extrasexual organs (such as musculocartilage development, nervous system development, etc.). Additionally, it has been suggested that DMRTs may be involved in the cancer development and progression (such as prostate cancer, breast cancer, lung cancer, etc.). This review summarizes the research progress about the mammalian DMRTs' structure, function and its critical role in cancer development, progression and therapy (mainly in human and mice), which suggests that DMRT gene could be a candidate gene in the study of tumor formation and therapeutic strategy.
Male ; Animals ; Humans ; Mice ; Transcription Factors/genetics* ; Mammals/metabolism* ; Cell Differentiation ; Neoplasms/genetics*

Objective:To investigate the effect of preoperative hemoglobin (Hb) level on the risk of developing acute kidney injury (AKI) after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI).Methods:A retrospective study was conducted. The hospitalized patients diagnosed with AMI who underwent PCI from May 2015 to May 2020 in the department of cardiology in the Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University were enrolled. According to the serum creatinine (SCr) level before and after interventional therapy, the patients were divided into an AKI group and a non-AKI group. The difference in patients' Hb levels between the AKI and non-AKI groups was compared. Univariate and multivariate Logistic regression analyses were used to analyze the effects of Hb levels on the risk of AKI after interventional therapy in patients with AMI. Kaplan-Meier survival curve was used to evaluate the effects of Hb levels on patients with AMI in all-cause death in the hospital.Results:A total of 922 AMI patients were enrolled in this study, of which 165 patients (17.9%) developed AKI. Compared with the non-AKI group, female patients in the AKI group had a higher proportion [35.8% (59/165) vs. 26.9% (204/757)], older (age: 69.78±14.56 vs. 66.61±13.44), with a lower rate of smoking [42.4% (70/165) vs. 51.7% (391/757)] and a higher prevalence of hypertension [73.3% (121/165) vs. 63.5% (481/757)], however, the patients in AKI group also had a worse cardiac function [the proportion of Killip grade 3 or above was higher: 33.9% (56/165) vs. 13.9% (105/757)], lower Hb level (g/L: 127.61±22.18 vs. 132.79±19.45), and there were less patients using angiotensin converting enzyme inhibitor/angiotensin Ⅱreceptor blocker [ACEI/ARB, 60.0% (99/165) vs. 74.5% (564/757)] and more patients using diuretics [24.8% (41/165) vs. 17.7% (134/757)] in AKI group, the differences were statistically significant (all P < 0.05). Compared with non-AKI group, patients in AKI group had a longer operation time [operation time > 60 minutes: 4.2% (7/165) vs. 1.5% (11/757)] and received more contrast media during the operative procedure [contrast media > 100 mL: 16.4% (27/165) vs. 3.6% (27/757)], the individuals had a higher rate of intra-operative hypotension [16.4% (27/165) vs. 8.2% (62/757)], and more patients were implanted more than 2 stents [8.5% (14/165) vs. 3.6% (27/757), all P < 0.05]. Univariate Logistic regression analysis suggested that each 1 g/L increase in preoperative Hb level was associated with a 1.2% decrease in the risk of postoperative AKI [odds ratio ( OR) = 0.988, 95% confidence interval (95% CI) was 0.980-0.996, P = 0.003]. Meanwhile, for every 1 standard deviation increase in preoperative Hb level, the risk of postoperative AKI decreased by 22.1% ( OR = 0.779, 95% CI was 0.661-0.918, P = 0.003). The patients were divided into low, medium and high concentration groups according to Hb levels (Hb levels were < 110 g/L, 110-150 g/L, ≥ 150 g/L, respectively), and multivariate Logistic regression analysis showed that the risk of AKI was significantly reduced in the high concentration group compared with that in the low concentration group ( OR = 0.463, 95% CI was 0.241-0.888, P = 0.020). The Kaplan-Meier survival curve analysis indicated that the short term survival after coronary intervention in AMI patients with low Hb concentration was significantly lower than that in patients with medium and high Hb concentration (Log-Rank: &chi;2= 23.215, P < 0.001). Conclusions:Preoperative lower Hb level is an independent risk factor for postoperative AKI in AMI patients. AMI patients with lower Hb levels have an increased risk of all-cause mortality within 1 month after AMI.

Objective:To investigate the clinical characteristics of the severe trauma patients with Acute kidney injury (AKI) ,and analyze the risk factors and clinical prognosis.Methods:Clinical data of severe trauma patients admitted to ICU of Xiaolan Hospital of Southern Medical University, from July 2018 to December 2020 were retrospectively analyzed. Demographic data, basic diseases, critical disease score, serum creatinine, hemoglobin, treatment options, blood transfusion volume, and clinical outcomes were collected to establish a clinical database. AKI was diagnosed and graded according to the Kidney Disease Improving Global Outcomes (KDIGO) criterion, and trauma type was classified according to the main injury part. The clinical data and laboratory examination of different groups were compared to analyze the clinical characteristics and prognosis in severe trauma patients. The risk factors of AKI in severe trauma patients were analyzed by Logistic regression.Results:(1) A total of 175 patients with severe trauma were eligible for inclusion, and the incidence of AKI was 30.9%(54/175), including 29 patients with AKI stage 1(16.6%), 15 patients with AKI stage 2 (8.6%), and 10 patients with AKI stage 3 (5.7%). In the cohort, the rate of in-hospital renal replacement therapy was 4%, in-hospital mortality was 5.7%, and 28-day mortality was 16.6%. (2) The age, shock patients, ICU admission serum creatinine, APACHEⅡscore and ISS score of AKI group were significantly higher than those of non-AKI group ( P<0.05). There were no significant differences between the two groups in gender, underlying diseases (hypertension and diabetes), ICU admission hemoglobin level and contrast agent utilization rate( P>0.05). Compared with the non-AKI group, AKI group had higher rates of surgical treatment (63% vs. 44.6%), more blood transfusion [875(720,1110)mL & 670(610,750)mL], longer ICU stay [6(4,11)d & 4(2.5,7.5)d], and higher rates of mechanical ventilation (96.3% vs. 81%), renal replacement therapy rate (13% vs. 0), in-hospital mortality (13% vs. 2.5%) and 28-day mortality (25.9% vs. 12.4%), the differences were statistically significant ( P<0.05). (3) The incidence of AKI was different in patients with different types of severe trauma, and the abdominal trauma group with a highest rate (50%). The serum creatinine at ICU admission and the peak value during hospitalization in abdominal trauma group were significantly higher than those in other injury types ( P<0.05). (4) Logistic regression analysis showed Age [ OR=1.020, 95% CI(1.003,1.038), P=0.024], APACHEⅡscore [ OR=1.137, 95% CI(1.053,1.228), P=0.001], shock [ OR=1.102, 95% CI(0.906,1.208), P=0.034], ICU admission serum creatinine [ OR=1.068, 95% CI(1.036,1.102), P=0.000], surgical treatment [ OR=4.205, 95% CI(1.446,12.233), P=0.008], blood transfusion volume [ OR=1.006, 95% CI(1.002,1.009), P=0.001] were independent risk factors for AKI in severe trauma patients. Conclusions:Severe trauma patients yield a high incidence of AKI influencing clinical prognosis. The incidence of AKI varies with different types of severe trauma. Age, APACHEⅡscore, shock, ICU admission serum creatinine, surgical treatment, and blood transfusion volume are independent risk factors for AKI in severe trauma patients.

Objective:To develop and validate a clinical prediction model for the risk of malignant ventricular arrhythmia in patients with acute myocardial infarction (AMI) during hospitalization, and evaluate the effect of the prediction model.Methods:A retrospective study was conducted. A total of 2 649 patients with AMI admitted to cardiology department of Changzhou No.2 People's Hospital of Nanjing Medical University from December 2012 to August 2020 were enrolled. The clinical characteristics including gender, age, medical history, discharge diagnosis, vital signs during hospitalization, electrocardiogram characteristics at admission, laboratory examination indexes, interventional treatment, drug usage, malignant ventricular arrhythmias [mainly included sustained ventricular tachycardia (VT), ventricular flutter or ventricular fibrillation (VF)], and death were recorded. All patients were divided into two groups according to whether VT/VF occurred during their hospitalization. Independent risk factors for VT/VF during hospitalization were evaluated by multivariate Logistic regression analysis, and a clinical prediction model was constructed. The receiver operating characteristic curve (ROC curve) was plotted, and the area under ROC curve (AUC) was calculated to evaluate the accuracy of the prediction model.Results:A total of 2 649 eligible patients with AMI were enrolled, of whom 134 (5.06%) developed VT/VF during hospitalization. The in-hospital mortality rate in VT/VF group was significantly higher than that in non-VT/VF group (38.1% vs. 1.7%, P < 0.01). Compared with the non-VT/VF group, the patients in the VT/VF group with lower systolic blood pressure [SBP (mmHg, 1 mmHg = 0.133 kPa): 125.9±28.2 vs. 132.0±24.2], higher random blood glucose (mmol/L: 8.6±4.8 vs. 7.4±3.7), worse cardiac function [Killip heart function grade ≥ 3: 36.6% vs. 10.7%, left ventricular ejection fraction (LVEF) < 0.50: 56.7% vs. 33.6%, frequent premature ventricular contractions: 12.7% vs. 1.2%] and more hypokalemia (46.3% vs. 17.3%), with significant differences (all P < 0.05). Multivariate Logistic regression analysis showed that Killip classification of cardiac function ≥ 3 [odds ratio ( OR) = 3.540, 95% confidence interval (95% CI) was 2.336-5.363], random blood glucose > 11.1 mmol/L ( OR = 1.841, 95% CI was 1.171-2.893), LVEF < 0.50 ( OR = 0.546, 95% CI was 0.374-0.797), frequent premature ventricular contractions ( OR = 12.361, 95% CI was 6.077-25.144), potassium < 3.5 mmol/L ( OR = 4.268, 95% CI was 2.910-6.259), SBP < 90 mmHg ( OR = 0.299, 95% CI was 0.150-0.597) and creatinine (Cr) > 100 μmol/L ( OR = 2.498, 95% CI was 1.170-5.334) were independent risk factors for VT/VF in patients with AMI (all P < 0.05). The clinical prediction model of VT/VF risk was constructed based on the variables selected by multivariate regression analysis. The ROC curve analysis showed that the AUC of the model in predicting VT/VF was 0.779 (95% CI was 0.735-0.823, P < 0.001); the optimal cut-off value of the model was 17, the sensitivity was 76.1%, the specificity was 67.3%. Conclusions:The incidence of VT/VF during hospitalization of AMI patients significantly increases the risk of in-hospital death. The independent risk factors of VT/VF are Killip grade ≥ 3, random blood glucose > 11.1 mmol/L, LVEF < 0.50, frequent ventricular premature beats, potassium < 3.5 mmol/L, SBP < 90 mmHg and Cr > 100 μmol/L. The newly constructed clinical prediction model has certain predictive value for the occurrence risk of VT/VF.

Objective:To investigate the clinical value of neuron specific enolase (NSE) and bispectral index (BIS ) in predicting the neurological prognosis in patients with severe intracerebral hemorrhage.Methods:Patients with severe intracerebral hemorrhage admitted to the ICU of Xiaolan Hospital of Southern Medical University from January 2019 to December 2020 were selected, and serum NSE detection and BIS monitoring were performed at an early stage. According to the Glasgow outcome scale (GOS) at 90 days after intracerebral hemorrhage, the patients were divided into the good neurologic prognosis group (GOS 4-5) and poor neurologic prognosis group (GOS 1-3). The levels of NSE and BIS between the two groups were compared. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the predictive value of NSE, BIS and their combination in predicting neurological prognosis.Results:A total of 126 patients with severe intracerebral hemorrhage were enrolled in this study, and 32 patients (25.4%) had poor neurological prognosis. The level of NSC in the poor neurological prognosis group was significantly higher than that in the good neurologic prognosis group [28 (13.7, 50.4) ng/mL vs. 13.5 (9.6, 18.5) ng/mL, P < 0.05], while the BIS level was significantly lower than that in the good neurologic prognosis group [32 (25.2, 45) vs. 55 (48, 62.2), P <0.05]. For detection of poor neurologic outcome in patients with severe intracerebral hemorrhage, NSE and BIS yielded the AUC values of 0.768 (0.685, 0.839) and 0.866 (0.793, 0.920), respectively, with cut-off values of 21.7 ng/mL and 47, respectively. The combination of NSE and BIS yielded a remarkably higher AUC value of 0.927 (0.867, 0.966) for predicting poor neurologic outcome than each index alone ( P<0.05). Conclusions:Early monitoring of NSE and BIS can effectively predict the neurological prognosis of patients with severe intracerebral hemorrhage, and the combination of NSE and BIS can further improve the prediction efficiency.

Objective:To construct and evaluate a decision tree based on biomarkers for predicting severe acute kidney injury (AKI) in critical patients.Methods:A prospectively study was conducted. Critical patients who had been admitted to the department of critical care medicine of Xiaolan Hospital of Southern Medical University from January 2017 to June 2018 were enrolled. The clinical data of the patients were recorded, and the biomarkers, including serum cystatin C (sCys C) and urinary N-acetyl-β-D-glucosaminidase (uNAG) were established immediately after admission to intensive care unit (ICU), and the end points were recorded. The test cohort was established with patient data from January to December 2017. The decision tree classification and regression tree (CART) algorithm was used, and the best cut-off values of biomarkers were used as the decision node to construct a biomarker decision tree model for predicting severe AKI. The accuracy of the decision tree model was evaluated by the overall accuracy and the receiver operating characteristic (ROC) curve. The validation cohort, established on patient data from January to June 2018, was used to further validate the accuracy and predictive ability of the decision tree.Results:In test cohort, 263 patients were enrolled, of whom 57 developed severe AKI [defined as phase 2 and 3 of Kidney Disease: Improving Global Outcomes (KDIGO) criterion]. Compared with patients without severe AKI, severe AKI patients were older [years old: 64 (49, 74) vs. 52 (41, 66)], acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score were higher [23 (19, 27) vs. 15 (11, 20)], the incidence of hypertension, diabetes and other basic diseases and sepsis were higher (64.9% vs. 40.3%, 28.1% vs. 10.7%, 63.2% vs. 29.6%), the levels of sCys C and uNAG were higher [sCys C (mg/L): 1.38 (1.12, 2.02) vs. 0.79 (0.67, 0.98), uNAG (U/mmol Cr): 5.91 (2.43, 10.68) vs. 2.72 (1.60, 3.90)], hospital mortality and 90-day mortality were higher (21.1% vs. 4.4%, 52.6% vs. 13.1%), the length of ICU stay was longer [days: 6.0 (4.0, 9.5) vs. 3.0 (1.0, 6.0)], and renal replacement therapy requirement was higher (22.8% vs. 1.9%), with statistically significant differences (all P < 0.05). ROC curve analysis showed that the areas under ROC curve (AUC) of sCys C and uNAG in predicting severe AKI were 0.857 [95% confidence interval (95% CI) was 0.809-0.897) ] and 0.735 (95% CI was 0.678-0.788), and the best cut-off values were 1.05 mg/L and 5.39 U/mmol Cr, respectively. The structure of the biomarker decision tree model constructed by biomarkers were intuitive. The overall accuracy in predicting severe AKI was 86.0%, and AUC was 0.905 (95% CI was 0.863-0.937), the sensitivity was 0.912, and the specificity was 0.796. In validation cohort of 130 patients, this decision tree yielded an excellent AUC of 0.909 (95% CI was 0.846-0.952), the sensitivity was 0.906, and the specificity was 0.816, with an overall accuracy of 81.0%. Conclusion:The decision tree model based on biomarkers for predicting severe AKI in critical patients is highly accurate, intuitive and executable, which is helpful for clinical judgment and decision.