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Objective:To evaluate the performance of machine learning (ML) based on automated breast volume scanner (ABVS) radiomics in distinguishing benign and malignant BI-RADS 4 lesions.Methods:Between May to December 2020, patients with BI-RADS 4 lesions from the Affiliated Hospital of Southwest Medical University (Center 1) and Guangdong Provincial Hospital of Traditional Chinese Medicine (Center 2) were prospectively collected and divided into training cohort (Center 1) and external validation cohort (Center 2). The radiomics features of BI-RADS 4 lesions were extracted from the axial, sagittal and coronal ABVS images by MaZda software. In the training cohort, 7 feature selection methods and thirteen ML algorithms were combined in pairs to construct different ML models, and the 6 models with the best performance were verified in the external validation cohort to determine the final ML model. Finally, the diagnostic performance and confidence (5-point scale) of radiologists (R1, R2 and R3, with 3, 6 and 10 years of experience, respectively) with or without the model were evaluated.Results:①A total of 251 BI-RADS 4 lesions were enrolled, including 178 lesions (91 benign, 87 malignant) in the training cohort and 73 lesions (44 benign, 29 malignant) in the external validation cases. ②In the training cohort, the 6 ML models (DNN-RFE, AdaBoost-RFE, LR-RFE, LDA-RFE, Bagging-RFE and SVM-RFE) had the best diagnostic performance, and their AUCs were 0.972, 0.969, 0.968, 0.968, 0.967 and 0.962, respectively. ③In the external validation cohort, the DNN-RFE still had the best performance with the AUC, accuracy, sensitivity, specificity, PPV and NPV were 0.886, 0.836, 0.934, 0.776, 86.8% and 82.5%, respectively. ④Before model assistance, R1 had the worst diagnostic performance with the accuracy, sensitivity, specificity, PPV and NPV were 0.680, 0.750, 0.640, 57% and 81%, respectively. After model assistance, the diagnostic performance of R1 was significantly improved ( P=0.039), and its diagnostic sensitivity, specificity, accuracy, PPV and NPV improved to 0.730, 0.810, 0.930, 68% and 94%; while the improvement of R2 and R3 were not significantly ( P=0.811, 0.752). Meanwhile, the overall diagnostic confidence of the 3 radiologists increased from 2.8 to 3.3 ( P<0.001). Conclusions:The performance of ML based on ABVS radiomics in distinguishing between benign and malignant BI-RADS 4 lesions is good, which may improve the diagnostic performance of inexperienced radiologists and enhance diagnostic confidence.
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As a ligand-dependent transcription factor,retinoid-associated orphan receptor γt(RORyt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the pro-gression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORyt to decrease Th17 cell development and IL-17 production.Several RORyt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORyt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORyt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORyt inhibitors were summarized,with an emphasis on their optimization from lead compounds,ef-ficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.
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Ulcerative colitis (UC) is one of types of inflammatory bowel disease with high recurrence. Recent studies have highlighted that microbial dysbiosis as well as abnormal gut immunity are crucial factors that initiate a series of inflammatory responses in the UC. Modulating the gut microbiota-intestinal immunity loop has been suggested as one of key strategies for relieving UC. Many Chinese herbal medicines including some of single herb, herbal formulas and the derived constituents have been reported with protective effect against UC through modulating gut microbiome and intestinal immunity. Some clinical trials have shown promising results. This review thus focused on the current knowledge on using Chinese herbal medicines for treating UC from the mechanism aspects of regulating intestinal homeostasis involving microbiota and gut immunity. The existing clinical trials are also summarized.
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Interference with quorum sensing(QS)represents an antivirulence strategy with a significant promise for the treatment of bacterial infections and a new approach to restoring antibiotic tolerance.Over the past two decades,a novel series of studies have reported that quorum quenching approaches and the discovery of quorum sensing inhibitors(QSIs)have a strong impact on the discovery of anti-infective drugs against various types of bacteria.The discovery of QSI was demonstrated to be an appropriate strategy to expand the anti-infective therapeutic approaches to complement classical antibiotics and antimicrobial agents.For the discovery of QSIs,diverse approaches exist and develop in-step with the scale of screening as well as specific QS systems.This review highlights the latest findings in strategies and methodologies for QSI screening,involving activity-based screening with bioassays,chemical methods to seek bacterial QS pathways for QSI discovery,virtual screening for QSI screening,and other potential tools for interpreting QS signaling,which are innovative routes for future efforts to discover additional QSIs to combat bacterial infections.
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OBJECTIVES@#To coat a zirconia surface with silica-zirconia using a dip-coating technique and evaluate its effect on resin-zirconia shear bond strength (SBS).@*METHODS@#A silica-zirconia suspension was prepared and used to coat a zirconia surface using a dip-coating technique. One hundred and eighty-nine zirconia disks were divided into three groups according to their different surface treatments (polishing, sandblasting, and silica-zirconia coating). Scanning electron microscopy (SEM), energy dispersive X-ray (EDX), and X-ray diffraction (XRD) were used to analyze the differently treated zirconia surfaces. Different primer treatments (Monobond N, Z-PRIME Plus, and no primer) were also applied to the zirconia surfaces. Subsequently, 180 composite resin cylinders (Filtek Z350) were cemented onto the zirconia disks with resin cement (RelyX Ultimate). The SBS was measured after water storage for 24 h or 6 months. The data were analyzed by two-way analysis of variance (ANOVA).@*RESULTS@#SEM and EDX showed that the silica-zirconia coating produced a porous layer with additional Si, and XRD showed that only tetragonal zirconia was on the silica-zirconia-coating surface. Compared with the control group, the resin-zirconia SBSs of the sandblasting group and silica-zirconia-coating group were significantly increased (@*CONCLUSIONS@#Dip-coating with silica-zirconia might be a feasible way to improve resin-zirconia bonding.
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Long-term primary culture of mammalian cells has been always difficult due to unavoidable senescence. Conventional methods for generating immortalized cell lines usually require manipulation of genome which leads to change of important biological and genetic characteristics. Recently, conditional reprogramming (CR) emerges as a novel next generation tool for long-term culture of primary epithelium cells derived from almost all origins without alteration of genetic background of primary cells. CR co-cultures primary cells with inactivated mouse 3T3-J2 fibroblasts in the presence of RHO-related protein kinase (ROCK) inhibitor Y-27632, enabling primary cells to acquire stem-like characteristics while retain their ability to fully differentiate. With only a few years' development, CR shows broad prospects in applications in varied areas including disease modeling, regenerative medicine, drug evaluation, drug discovery as well as precision medicine. This review is thus to comprehensively summarize and assess current progress in understanding mechanism of CR and its wide applications, highlighting the value of CR in both basic and translational researches and discussing the challenges faced with CR.
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Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components. Recent epidemiological and clinical studies strongly support that vitamin D supplementation is associated with reduced cancer risk and favorable prognosis. Experimental results suggest that vitamin D not only suppresses cancer cells, but also regulates tumor microenvironment to facilitate tumor repression. In this review, we have outlined the current knowledge on epidemiological studies and clinical trials of vitamin D. Notably, we summarized and discussed the anticancer action of vitamin D in cancer cells, cancer stem cells and stroma cells in tumor microenvironment, providing a better understanding of the role of vitamin D in cancer. We presently re-propose vitamin D to be a novel and economical anticancer agent.
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Objective To evaluate left ventricular geometry and function in elderly type 2 diabetic patients with normal and high pulse pressure by using three-dimensional speckle-tracking echocardiography (3DSTE).Methods A total of 76 elderly non-hypertensive type 2 diabetic patients were divided into type 2 diabetic combined with high pulse pressure group (n=36;24 h pulse pressure ≥60 mmHg) and type 2 diabetic combined with normal pulse pressure group (n=40).Forty age-and sex-matched healthy volunteers with normal 24 h pulse pressure were recruited as control group.3DSTE was performed in all participants.Results Significant differences in left ventricle geometry were found among the three groups (x2 =8.428,P=0.015),and concentric geometry was most prevalent in type 2 diabetic patients with high pulse pressure group.Global longitudinal strain in type 2 diabetic patients with normal pulse pressure group was significantly lower than that of control group (P＜0.001).The type 2 diabetic combined with high pulse pressure group showed severely lower strain values in all directions compared with control group and type 2 diabetic combined with normal pulse pressure group (all P＜0.05).Conclusion 3DSTEC can detect subclinical cardiac abnormalities in elderly type 2 diabetic patients with normal and high pulse pressure.
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OBJECTIVE: To improve dispensing rate of automatic dispensing equipment, and to shorten dispensing time.METHODS: Continuous quality improvement (CQI) group was established, and COI was conducted by using PDCA (Plan, Do, Check, Action) cycle. The influencing factors for slow drug delivery of automatic dispensing equipment were analyzed to set up the target, adjust multi-package drugs, develop appropriate improvement plans and implementation methods, monitor result and evaluate effect (calculated the first 10 in usage frequency of the multi-package drugs). RESULTS: Through adjusting the specification and list of multi-package drugs, the utilization rate of multi-package drug increased from 63. 91％ to 86. 23％ of 10 drugs during Jun. -Oct. in 2016; compared with the single-package dispensing mode, and dispensing time shortened 7. 86-13. 73 h per month of 10 drugs. CONCLUSIONS: Through the CQI, the dispensing rate of automation dispensing equipment is greatly increased by drug multi-package dispensing mode.
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Objective To evaluate the short-term clinical effectiveness and feasibility of thoracic endovascular aortic repair(TEVAR) with in situ laser fenestration.Methods 24 patients who received TEVAR and in situ laser fenestration from January 2017 to March 2017 were retrospectively reviewed.Include 24 patients,19 males,5 females,with an average age of (54.00 ± 13.58) years old.The clinical data,including post-operative symptoms,hospitalization days,the success rate,postoperative complications,30-day fatality ratio,the patency rate of branch stents,endoleak,etc.Results The mean hospitalization time was(12.81 ±4.18) days.32 aortic arch branch vessels were treated using in situ laser fenestration,30 succeed in laser fenestration,surgical success rate was 93.8％.One case with postoperative paraplegia recovered after treatment,another one with the left common carotid incision hematoma recovered too.The incidence of operation-related complications was 8.3 ％.After the surgery 1 patient died,30-day fatality ratio of 4.2％.Imaging surveillance with computed tomography angiography(CTA) was performed one month later after the operation,the patency rate of branch stents was 100％,one case was found endoleak.Conclusion For revascularizating aortic arch branch vessels during TEVAR,in situ laser fenestration has an excellent successful rate and short-term curative effect,while the long-term surveillance is needed.
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Objective·To evaluate the clinical value of two-dimensional ultrasound combined with four-dimensional color Doppler ultrasound in the diagnosis of uterine space-occupying lesion.Methods·A total of 75 patients with uterine space-occupying lesion were enrolled in this study from March 2015 to February 2016 at Hospital of Southwest Medical University.Patients received both two-dimensional ultrasound and four-dimensional color Doppler ultrasound to determine the location,number and nature of the lesions,as well as the clinical staging of malignant lesions,then the diagnostic accuracy was evaluated.Results·Among 75 patients,there were 26 cases with endometrial carcinoma,21 cases with hysteromyoma,16 cases with metropolypus,and 12 cases with uterine adenomyosis.The diagnostic accuracy of two-dimensional ultrasound combined with four-dimensional color Doppler ultrasound for the uterine space-occupying lesion was 88.0％,which was significantly higher than that of two-dimensional ultrasound (64.0％) (P＜0.05).What's more,the diagnostic accuracy of two-dimensional ultrasound combined with four-dimensional color Doppler ultrasound for the clinical staging of endometrial carcinoma was 88.5％,which was significantly higher than that of two-dimensional ultrasound (61.5％) (P＜0.05).Conclusion·Two-dimensional ultrasound combined with four-dimensional color Doppler ultrasound is more effective to improve the diagnostic accuracy of uterine space occupying lesion and clinical staging of endometrial carcinoma in comparison with two-dimensional ultrasound,which will favor the clinical strategy for the treatment of uterine space-occupying lesion.
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Objective To investigate the value of Doppler ultrasound in the eady diagnosis,monitoring and assessing of renal damage in neonatal asphyxia.Methods A total of 60 cases of neonates within 24 h were divided into severe asphyxia group (Apgar score 0-3),mild asphyxia group (Apgar score 4-7) and healthy control group (Apgar score 8-10) according to Apgar score at 1 min after born.Then the peak systolic velocity (PSV),end diastolic velocity (EDV) and resistance index (RI) of renal artery were obtained by Doppler ultrasound within 24 h,on day 3,day 7,and day 10.The level of serum cystain C (sCysC) was also recorded accordingly.Results Within 24 h,compared with healthy control group,the PSV and EDV in severe asphyxia group and mild asphyxia group decreased (all P＜0.05),while RI increased (all P＜0.05).The PSV in mild asphyxia group returned to normal in 3 days,EDV and RI returned to normal in 10 days,there were no statistically significant difference compared with healthy control group (all P＞0.05).The PSV,EDV and RI in severe asphyxia group were still significantly differences compared with healthy control group on day 10 (all P＜0.05).Within 24 h and on day 3,sCysC in the mild asphyxia group increased obviously compared with healthy control group (both P＜0.05).On day 7 and day 10,the differences of sCysC was not statistically significant between mild asphyxia group and healthy control group (both P＞0.05).Compared with healthy control group,the sCysC in severe asphyxia group increased significantly (all P＜0.05) on every time point.PSV and EDV were negatively correlated with sCysC,RI was positively correlated with sCysC.Conclusion Changes in renal function can be reflected soon by index of renal blood flow PSV,EDV and RI.
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Pulmonary artery hypertension (PAH ) is a chronic progressive disease characterized by a persistent elevation of pul-monary vascular pressure,and the disease would limit the right ventricular function severely,fail the organ and even lead to death in the end.The histopathological change of PAH is fea-tured by the restructuring of pulmonary vessels,and the abnor-mal reproduction of pulmonary artery smooth muscle cells (PASMCs)in peripheral vessels is the major pathological basis of pulmonary vascular restructuring.This paper mainly reviews the research advances on signal transduction mechanisms and their inhibitors in promoting the proliferation of pulmonary artery smooth muscle cells.
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Objective_To investigate the effects of hypoxia-inducible factor-1 alpha ( HIF-1α) inhibitor YC-1 on hy-poxia induced human pulmonary artery smooth muscle cells ( HPASMCs) proliferation, apoptosis and the expression of P53, and to explore the molecular mechanism in the processes.Methods_HPASMCs were cultured in DMEM me-dium supplemented with 10%FBS in vitro.Then divided them into four groups:normoxia, hypoxia and hypoxia+YC-1(0.01 and 0.05 mmol/L).Cell proliferation was measured by CCK-8 and apoptosis was detected by flow cytom-etry.The expressions of HIF-1αand P53 were tested by Western blot, and the mRNA expression of P53 was tested by RT-PCR.Results_Hypoxia can promote the proliferation of HPASMCs.Treatment of HPASMCs with different concentrations of YC-1 intervention for 24h obviously dropped proliferation rate (P<0.05), and the apoptosis rate increased significantly (P<0.05).YC-1 can also down-regulate the expression of HIF-1αand up-regulate the ex-pression of P53 significantly ( P<0.05 ) .Conclusions_YC-1 can inhibit hypoxia-induced HPASMCs proliferation and promote apoptosis, the mechanism is potentially related to the up-regulation of P53 expression.
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@#Objective To construct recombinant adenovirus vector carrying the human HSP75 gene and detect its expression in C17.2 neural stem cells. Methods HSP75 gene was amplified from plasmid carrying the human HSP75 gene and inserted to the polyclonal site of adenovirus shuttle plasmid pHBAd-MCMV-GFP. HEK293 cells were co-transfected with the constructed recombinant shuttle plasmid pHBAd-MCMV-HSP75-GFP and large adenovirus helper plasmid pHBAd-BHGloxΔE1,3 Cre in mediation of LipofiterTM. The recombinant adenovirus was obtained and the viral titer was examined using the method of TCID50. The transfection and expression of HSP75 was detected by fluorescence microscope, flow cytometer and Western blotting. Results Restriction digestion, sequencing analysis and PCR amplification revealed the successful construction of recombinant shuttle plasmid and recombinant adenovirus. The titer of recombinant adenovirus was 1.0×1010 PFU/ml. Western blotting indicated HSP75 gene could be expressed effectively in neural stem cells after transfection. Conclusion The recombinant adenovirus vector carrying HSP75 gene was successfully constructed and can be expressed after transfected in C17.2 neural stem cells.
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Objective To construct recombinant adenovirus vector carrying the human HSP75 gene and detect its expression in C17.2 neural stem cells. Methods HSP75 gene was amplified from plasmid carrying the human HSP75 gene and inserted to the polyclonal site of adenovirus shuttle plasmid pHBAd-MCMV-GFP. HEK293 cells were co-transfected with the constructed recombinant shuttle plasmid pH-BAd-MCMV-HSP75-GFP and large adenovirus helper plasmid pHBAd-BHGloxΔE1,3 Cre in mediation of LipofiterTM. The recombinant ad-enovirus was obtained and the viral titer was examined using the method of TCID50. The transfection and expression of HSP75 was detect-ed by fluorescence microscope, flow cytometer and Western blotting. Results Restriction digestion, sequencing analysis and PCR amplifica-tion revealed the successful construction of recombinant shuttle plasmid and recombinant adenovirus. The titer of recombinant adenovirus was 1.0×1010 PFU/ml. Western blotting indicated HSP75 gene could be expressed effectively in neural stem cells after transfection. Conclu-sion The recombinant adenovirus vector carrying HSP75 gene was successfully constructed and can be expressed after transfected in C17.2 neural stem cells.
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Objective In this study ,to explore the relationship between the renal blood flow PI ,and the AKI was caused by CPB .Methods 14 cases with heart disease were accepted .The renal aorta and renal segmental artery PI of all cases were monitored by the CDFI at the preoperative and postoperative 1 h ,2 h ,4 h ,8 h ,16 h ,24 h .The renal blood urea nitrogen (Urea) ,uric acid (UA) ,creatinine (Crea) ,were detected at the same time .All datas for statistical analysis .Results The renal aorta PI was higher at the postoperative 1 h ,2 h ,4 h ,8 h ,16 h than that at the preoperative .The renal segmental artery PI was higher at the postoperative 1 h ,2 h ,4 h ,16 h than that at the preoperative .The renal blood flow PI was positively correlated with Urea ,UA and Crea .Conclu-sion The renal aorta ,renal segmental artery PI was positively correlated with Urea ,UA and Crea after CPB .The PI may be seen as an evaluation index to assess AKI after CPB .
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Objective To explore the value of the laparoscopic ultrasonography (LUS) in laparoscopic common bile duct explora-tion(LCBDE) .Methods 47 cases with cholecystolithiasis combined with bile duct dilatation or abnormal liver function were tested by conventional ultrasound ,magnetic resonance cholangiopancreatgraphy (MRCP) CT and LUS after LCBDE .All results were com-pared with the surgical findings and the intraoperative biliary endoscopy results .Results The diagnosis coincidence rate of conven-tional ultrasonography ,CT ,MRCP and LUS in 47 cases were 85 .1% ,72 .3% ,95 .7% ,100 .0% respectively .6 cases completed the surgery under the guidance of LUS ,1 case was converted to open surgery .Conclusion LUS is an examination method to avoid bile duct injury effectively and reduce postoperative residual stone in LCBDE .
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Objective To apply the real-time gray scale contrast-enhanced ultrasonography(CEUS) with quantitative analysis technique to monitor the change of the renal cortex blood perfusion before and after Salvia miltiorrhiza treatment of rabbit renal is-chemia-reperfusion injury and to investigate the application value of the ultrasound contrast for evaluating the effect of medication in the treatment of rabbit renal ischemia-reperfusion injury (IRI) .Methods The rabbit right kidney was resected and the left renal pedicle was occluded for 60 min ischemia ,then the perfusion was recovered for establishing the IRI model .Salvia miltiorrhiza injec-tion was given for observing the pathological changes of the left kidney and the renal cortex blood prefusion under the contrast-en-hanced ultrasonography .The parameters of renal cortex blood perfusion were quantitatively analyzed by the time-intension curves . Results After IRI occurrence ,the time-intensity curve (TIC) of the rabbit renal cortex was slowly ascended .The time to peak (TTP) was extened and the rising slope(Grad) of the curve ascending branch was declined (P< 0 .05);after Salvia miltiorrhiza treatment ,TTP decreased and Grad increased obviously(P<0 .05) .Conclusion CEUS combined with quantitative analysis can re-flect the renal blood perfusion abnormity caused by ischemia-reperfusion and discover the change of the renal blood perfusion after medication treatment .
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Purpose To explore the clinical value of color Doppler ultrasound in monitoring hemodynamic changes in main renal artery of neonatal asphyxia. Materials and Methods A total of 60 cases of neonatal asphyxia were divided into mild asphyxia (38 cases) and severe asphyxia (22 cases) according to Apgar score 1 min after born. Then the peak systolic velocity (Vs), the end diastolic velocity (Vd) and the resistance index (RI) of the main renal artery were obtained by color Doppler ultrasound on day 1 and day 3;the level of endothelin-1 (ET-1) was also recorded accordingly. The above results were compared with those of 20 cases of healthy full-term new born infants. Results On day 1, Vs and Vd of the main renal artery in the groups with mild asphyxia and severe asphyxia were both lower than those in healthy group (P<0.05), but RI was higher (P<0.05), with more dramatic changes in the group with severe asphyxia (P<0.05). On day 3, Vs and Vd in the groups with mild asphyxia and severe asphyxia reduced compared with those on day 1, whilst RI was higher than that on day 1. Vd and RI in the group with severe asphyxia changed more significantly (P<0.01). As to the value of ET-1, both groups with mild asphyxia and severe asphyxia showed higher level than healthy group (P<0.01). More dramatic increase appeared in the group with severe asphyxia (P<0.05). In the groups with mild asphyxia and severe asphyxia, the Vs and Vd of the main renal artery were negatively correlated with ET-1 on day 1 and day 3 (r=-0.823,-0.845;P<0.01), while the RI was positively correlated with ET-1 (r=0.785, P<0.01). Conclusion Both color Doppler ultrasound imaging and neonatal urine ET-1 test can reflect degree of renal injury after neonatal asphyxia dynamically and noninvasively, which can be used to evaluate the injury severity.