Research progress of adipokines and diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic retinopathy(DR)is one of the common microangiopathy in diabetes and the main cause of blindness in adults. It can be seen that it is very important to find the specific target of DR prevention and treatment. Adipose tissue is not only an energy storage tissue, but also an active endocrine organ, which can release a variety of cytokines, called adipokines. Studies have shown that adipokines play an important role in the occurrence and development of DR. Adipokines can not only directly act on vascular endothelium through blood circulation, but also indirectly affect vascular endothelial function by affecting the activity of sympathetic nervous system and insulin sensitivity, which leads to dysfunction of vascular endothelial cells, increased retinal vascular permeability, neurodegeneration and neovascularization, and finally leads to the destruction of blood-retinal barrier. In recent years, the role of some new adipokines in DR has been paid more and more attention. This paper reviews the related research of several new adipokines in DR.

Hydroxysafflor yellow A intervenes astrocyte lipocalin 2 expression after cerebral ischemia/reperfusion injury / 中国组织工程研究

BACKGROUND:Ischemic stroke is a serious threat to human health.After ischemia and hypoxia,astrocyte expresses lipocalin-2 in large amounts to aggravate brain injury,but the specific mechanism is not clear.Hydroxysafflor yellow A has anti-ischemia,anti-oxidation,anti-thrombosis and anti-inflammatory effects.However,whether hydroxysafflor yellow A affects the expression of lipocalin-2 in astrocytes after cerebral ischemia and hypoxia and its mechanism are not clear. OBJECTIVE:To investigate the effect and mechanism of hydroxysafflor yellow A on the expression of lipocalin-2 in astrocytes after cerebral ischemia and reperfusion. METHODS:(1)Thirty adult SD rats were randomly divided into three groups:sham operation group,middle cerebral artery occlusion and reperfusion group,and hydroxysafflor yellow A group.The middle cerebral artery occlusion and reperfusion model was established in the latter two groups,and hydroxysafflor yellow A group was intraperitoneally injected with 12 mg/kg hydroxysafflor yellow A after reperfusion.Longa score was used to evaluate the degree of neurological impairment.Infarct volume was determined by TTC staining.JAK2/STAT3 pathway and lipocalin-2 expression were detected by western blot assay and immunofluorescence.Levels of interleukin 1β,interleukin 6 and tumor necrosis factor α were detected by ELISA.(2)Astrocytes were divided into four groups:Normal group,glucose-oxygen deprivation group,hydroxysafflor yellow A group and AG490 group.In the latter three groups,glucose-oxygen deprivation and glucose-oxygen recovery models were established.Astrocytes were treated with 75 μmol/L hydroxysafflor yellow A and 10 μmol/L tyrosine phosphorylation inhibitor AG490 for 8 hours during glucose-oxygen deprivation,respectively.The mechanism of hydroxysafflor yellow A on lipocalin-2 was further verified. RESULTS AND CONCLUSION:(1)Compared with the sham operation group,cerebral infarction was significantly increased in the middle cerebral artery occlusion and reperfusion group,accompanied by aggravated neurological impairment(P<0.01).Hydroxysafflor yellow A treatment could reduce cerebral infarction volume and improve neurological function(P<0.01).(2)The expressions of p-JAK2,p-STAT3 and lipocalin-2 in the middle cerebral artery occlusion and reperfusion group were higher than those in the sham operation group(P<0.01).Hydroxysafflor yellow A treatment reduced the expressions of JAK2,STAT3 and lipocalin-2(P<0.01).(3)The expression levels of interleukin 1β,interleukin-6 and tumor necrosis factor α in the middle cerebral artery occlusion and reperfusion group were higher than those in the sham operation group(P<0.01).Hydroxysafflor yellow A inhibited the expressions of interleukin 1β,interleukin-6 and tumor necrosis factor α(P<0.01).(4)In vitro,the expressions of p-JAK2,p-STAT3 and lipocalin-2 in the glucose-oxygen deprivation group were significantly higher than those in the normal group(P<0.01).After adding AG490,the phosphorylation of JAK2 and STAT3 decreased,and the expression of lipocalin-2 was inhibited(P<0.01).The results suggest that hydroxysafflor yellow A may inhibit the expression of lipocalin-2 in astrocytes after ischemia and hypoxia by regulating the JAK2/STAT3 signaling pathway,thereby reducing brain injury.

Study and validation of biomarkers in serum of patients with acute and chronic kidney injury / 中国病理生理杂志

AIM:The aim of this study is to investigate the clinical utility of neutrophil gelatinase-associated lipocalin(NGAL)and other biomarkers in serum for patients with acute and chronic kidney injury.METHODS:A total of 171 patients with acute kidney injury(AKI)and 209 patients with chronic kidney disease(CKD)who sought medical care at the Third Affiliated Hospital of Sun Yat-sen University in Guangzhou between January 2022 and July 2023 were in-cluded in this study.Data on potassium(K),sodium(Na),chloride(Cl),carbon dioxide(CO2),urea(Urea),and glu-cose(GLU)were collected from each group of participants.A total of 94 individuals who were deemed healthy and had un-dergone physical examinations within the same time frame were chosen as the control group.The serum NGAL levels of all three groups were measured using latex immunoturbidimetry.The diagnostic effectiveness of serum NGAL and other bio-markers in identifying acute and chronic kidney injury was analyzed.Multiple logistic regression equations were employed to examine the factors influencing the occurrence of AKI and CKD in patients.Additionally,receiver operating characteris-tic(ROC)curves were constructed to evaluate the clinical significance of these biomarkers in patients with kidney injury.RESULTS:Through bioinformatic analysis,it was suggested that NGAL may be a detection marker of kidney injury.Ac-cording to general data,in the AKI and the CKD groups,K,Na,CO2,Urea,GLU and NGAL levels were higher than those in the healthy control group(P＜0.05).Multivariate logistic regression equation analysis showed that Na,Urea,GLU and NGAL levels were all independent risk factors for AKI or CKD disease occurrence(P＜0.05).The ROC curve analysis showed that in the AKI group,the area under the curve(AUC)for Na,Urea,GLU and NGAL were 0.711,0.960,0.793 and 0.841,respectively(P＜0.01).In the CKD group,the AUC for Na,Urea,GLU and NGAL were 0.681,0.990,0.703 and 0.930,respectively(P＜0.01).The sensitivity and specificity of NGAL and Urea combined diagnosis for AKI were 81.9%and 61.1%,respectively,and those for CKD were 62.7%and 80.0%,respectively.CONCLUSION:Serum NGAL can serve as an indicator of acute and chronic kidney injury,and its combination with other biomarkers also has certain clinical application value in acute and chronic kidney injury.

Neutrophil gelatinase-associated lipocalin: a biochemical marker for acute kidney injury and long-term outcomes in patients presenting to the emergency department

INTRODUCTION@#Creatinine has limitations in identifying and predicting acute kidney injury (AKI). Our study examined the utility of neutrophil gelatinase-associated lipocalin (NGAL) in predicting AKI in patients presenting to the emergency department (ED), and in predicting the need for renal replacement therapy (RRT), occurrence of major adverse cardiac events (MACE) and all-cause mortality at three months post visit.@*METHODS@#This is a single-centre prospective cohort study conducted at Singapore General Hospital (SGH). Patients presenting to SGH ED from July 2011 to August 2012 were recruited. They were aged ≥21 years, with an estimated glomerular filtration rate <60 mL/min/1.73 m2, and had congestive cardiac failure, systemic inflammatory response syndrome or required hospital admission. AKI was diagnosed by researchers blinded to experimental measurements. Serum NGAL was measured as a point-of-care test.@*RESULTS@#A total of 784 patients were enrolled, of whom 107 (13.6%) had AKI. Mean serum NGAL levels were raised (P < 0.001) in patients with AKI (670.0 ± 431.9 ng/dL) compared with patients without AKI (490.3 ± 391.6 ng/dL). The sensitivity and specificity of NGAL levels >490 ng/dL for AKI were 59% (95% confidence interval [CI] 49%-68%) and 65% (95% CI 61%-68%), respectively. Need for RRT increased 21% per 100 ng/dL increase in NGAL (P < 0.001), whereas odds of death in three months increased 10% per 100 ng/dL increase in NGAL (P = 0.028). No clear relationship was observed between NGAL levels and MACE.@*CONCLUSION@#Serum NGAL identifies AKI and predicts three-month mortality.

The clinical significance of cord blood neutrophil gelatinase-associated lipocalin in neonates with perinatal hypoxic organ damage / 中国新生儿科杂志

Objective:To study the changes of cord blood neutrophil gelatinase-associated lipocalin (NGAL) under different levels of hypoxia at birth and its correlations with hypoxic organ damage (including liver, kidney and heart).Methods:From April to October 2022, all neonates born in our hospital were prospectively enroll in the study. The neonates without perinatal risk factors were assigned into the control group. The neonates with intrauterine distress or hypoxia during labor were assigned into the hypoxia group (no asphyxia at birth) and the asphyxia group (with asphyxia at birth). Cord blood was collected from the umbilical artery and cord blood gas (CBG) and NGAL were measured. Liver enzymes, kidney function and cardiac enzymes as biomarkers for hypoxic organ damage were measured 24~48 h after birth. The correlations of NGAL and the biomarkers were analyzed.Results:A total of 161 neonates were enrolled, including 91 in the control group, 49 in the hypoxia group and 21 in the asphyxia group. NGAL in the asphyxia group was significantly higher than the hypoxia group and the control group [(1.81±0.71) ng/ml vs. (1.22±0.53) ng/ml, (0.88±0.47) ng/ml], NGAL in the hypoxia group significantly higher than the control group ( P<0.05). NGAL was negatively correlated with Apgar score, pH and BE of CBG ( r<-0.3, P<0.05) and positively correlated with lactate, ALT, creatinine ( r>0.3, P<0.05). No significant correlations existed between NGAL and gender, gestational age, birth weight, mother's age, BMI and CK-MB ( P<0.05). ROC curve showed that sensitivity and specificity of NGAL for predicting hypoxic organ damage were 84.3% and 60.3%, respectively, with a cut-off value of 1.07 ng/ml. Conclusions:Cord blood NGAL may increase with the deterioration of hypoxia at birth and may be associated with hypoxic organ damage.

Study on the analysis on the clinical effect of hyperbaric oxygen chamber in treating the postoperatively malignant brain edema of craniocerebral trauma / 中国医学装备

Objective:To study the clinical effect of NBYY-BXDR-001 hyperbaric oxygen chamber in treating the postoperatively malignant brain edema of craniocerebral trauma,and the effects of that on the levels of matrix metalloproteinase-9(MMP-9),neutrophil gelatinase-associated lipocalin(NGAL),tenascin-C(TNC)and tumor necrosis factor-ɑ(TNF-ɑ).Methods:A total of 84 patients with postoperatively malignant brain edema of craniocerebral trauma who admitted to the hospital were selected,and they were divided into an observation group(45 cases received the interventional treatment of hyperbaric oxygen within postoperative 1-3 days)and a control group(39 cases received interventional treatment of hyperbaric oxygen within postoperative 4-10 days)according to the different therapeutic times of postoperative hyperbaric oxygen.The levels of serum MMP-9,NGAL,TNC and TNF-ɑof the two groups of patients were compared.The Glasgow Coma Scale(GCS)scores and the duration of brain edema of patients before and after treatment were recorded,and the mortality rates of the two groups of patients also were recorded.Results:There was no statistically significant difference in postoperative mortality rates between the two groups.The overall efficacy of the observation group was significantly better than that of the control group,and the difference was statistically significant(Z=-2.203,P<0.05).The GCS scores of the patients of the observation group at the 1st week,2nd week,3rd week and 4th week after surgery were significantly higher than that at the 1st d after surgery,and the differences were statistically significant(t=5.236,t=5.687,t=6.354,t=6.782,P<0.05),respectively.The serum MMP-9,NGAL,TNC and TNF-ɑ levels of the two groups of patients at the 1st week,2nd week,3rd week and 4th week after surgery were significantly lower than those at the 1st day after surgery,and the differences were statistically significant(Fobservation group= 125.127,F=98.224,F=137.791,F=105.226,Fcontrol group=113.370,F=73.363,F=115.520,F=84.069,P<0.05),respectively.At the 2nd,3rd and 4th week after surgery,the GCS scores of the observation group were significantly higher than those of the control group,and the serum MMP-9,NGAL,TNC and TNF-ɑ of the observation group were significantly lower than those of the control group,and the differences were statistically significant(tMMP-9=5.689,t=6.879,t=8.253,tNGAL=8.658,t=9.657,t=8.658,tTNC=6.587,t=6.354,t=6.859,tTNF-ɑ=7.898,t=8.654,t=8.256,P<0.05),respectively.Compared with the control group,the peak time and duration of brain edema of the observation group were significantly shortened,and the differences of them between two groups were statistically significant(t=2.064,t=-2.084,P<0.05),respectively.Conclusion:Early interventional treatment of hyperbaric oxygen in patients with postoperatively malignant brain edema of craniocerebral trauma can contribute to relieve postoperative brain edema and improve the treatment effect,which is related to the adjustment of hyperbaric oxygen for serum MMP-9,NGAL,TNC and TNF-ɑ levels.

Predictive value of serum neutrophil gelatinase-associated lipocalin for acute kidney injury in high-risk elderly patients / 中华老年医学杂志

Objective:To analyze the predictive value of neutrophil gelatinase-associated lipocalin(NGAL)in high-risk elderly patients with acute kidney injury(AKI).Methods:A retrospective study was conducted to collect 183 patients over 65 years old in the Department of Geriatrics, the First Affiliated Hospital of Nanjing Medical University from January 2018 to October 2019.The patients were combined with at least one risk factor.The diagnostic effect of NGAL for AKI prediction in high-risk patients was evaluated.According to the initial serum creatinine(SCr)and basic glomerular filtration rate(eGFR), the patients were divided into chronic kidney disease(CKD)group and non-CKD group.The optimal diagnostic threshold for A-on-C is determined by determining the area under the subject curve(AuROC). Univariate and independent predictors multivariate regression analysis was used to assess the risk of AKI.Results:The serum NGAL(NGAL)level in AKI group was higher than that in non-AKI group[702.5 μg/L(499.2, 813.2) vs.233.9 μg/L(147.2, 315.7), Z=8.002, P<0.001]. In CKD patients, serum NGAL in AKI group was higher than that in non-AKI group[1033 μg/L(845.5, 1447) vs.288.2 μg/L(221.4, 423.3), Z=4.867, P<0.001]. In all patients, model 3 with four variables showed better AKI prediction ability than model 0, 1 and 2( R2=0.743, P<0.001). In the CKD group, the AuROC of serum NGAL for AKI prediction was larger than that of CYS-C group, whereas in the non-CKD group, the AuROC of serum NGAL for AKI prediction was smaller than that of CYS-C group. Conclusions:Serum NGAL may serve as a useful biomarker for AKI prediction in AKI high-risk elderly patients.Especially in patients with CKD, Serum NGAL has a better predictive value for AKI than traditional indicators.

Effect of Shengmai Yin on Epithelial-Mesenchymal Transition of Nasopharyngeal Carcinoma Radioresistant Cells / 中国结合医学杂志

OBJECTIVE@#To investigate the mechanism by which Chinese medicine Shengmai Yin (SMY) reverses epithelial-mesenchymal transition (EMT) through lipocalin-2 (LCN2) in nasopharyngeal carcinoma (NPC) cells CNE-2R.@*METHODS@#Morphological changes in EMT in CNE-2R cells were observed under a microscope, and the expressions of EMT markers were detected using quantitative real-time PCR (RT-qPCR) and Western blot assays. Through the Gene Expression Omnibus dataset and text mining, LCN2 was found to be highly related to radiation resistance and EMT in NPC. The expressions of LCN2 and EMT markers following SMY treatment (50 and 100 µ g/mL) were detected by RT-qPCR and Western blot assays in vitro. Cell proliferation, migration, and invasion abilities were measured using colony formation, wound healing, and transwell invasion assays, respectively. The inhibitory effect of SMY in vivo was determined by observing a zebrafish xenograft model with a fluorescent label.@*RESULTS@#The CNE-2R cells showed EMT transition and high expression of LCN2, and the use of SMY (5, 10 and 20 µ g/mL) reduced the expression of LCN2 and reversed the EMT in the CNE-2R cells. Compared to that of the CNE-2R group, the proliferation, migration, and invasion abilities of SMY high-concentration group were weakened (P<0.05). Moreover, SMY mediated tumor growth and metastasis in a dose-dependent manner in a zebrafish xenograft model, which was consistent with the in vitro results.@*CONCLUSIONS@#SMY can reverse the EMT process of CNE-2R cells, which may be related to its inhibition of LCN2 expression. Therefore, LCN2 may be a potential diagnostic marker and therapeutic target in patients with NPC.

Expression and Clinical Significance of NGAL and Autophagy in Renal Ischemia/Reperfusion Injury in Rats / 医学研究杂志

Objective To investigate the changes and clinical significance of the expression of neutrophil gelatinase-associated li-pocalin(NGAL)and autophagy during different time of renal ischemia/reperfusion(I/R)injury in rats.Methods The rat renal I/R in-jury model was established,thirty male Wistar rats were divided by random number table method into sham operation group(Sham group)and I/R group,according to the different time of reperfusion after I/R injury,the I/R group was divided into 4subgroups:2h group,6h group,24h group,48h group.Blood,urine and renal tissue samples were collected at different time points,NGAL levels of blood and u-rineweredetectedbyenzyme-linkedimmunoadsordentassay(ELISA)method.Bloodureanitrogen(BU)and serum creatinine(SCr)were detected by automatic biochemical analyzer.Hematoxylin-eosin staining was used to detect the degree of histopathological injury and score the degree of injury.TdT-mediated dUTP nick end labeling(TUNEL)method was used to detect the apoptosis of renal tubular ep-ithelial cells;the expression of autophagy related genes LC3 and Beclin-1gene was detected by real-time quantitative polymerase chain reaction(RT-qPCR)method.Results The expression levels of NGAL in blood and urine were elevated in the 2h after I/R injury,and peaked at 6h of reperfusion,and showed a downward trend at 24h.BU and Scr values began to increase after the 6h reperfusion of I/R in-jury and peaked at 24h of reperfusion.TUNEL positive cells began to increase at 6h after I/R injury,the number of the highest was at 24h reperfusion of I/R injury.Hematoxylin-eosin staining showed that there were different degrees of swelling and necrosis of renal tubular epithelial tissue in all groups after I/R injury.The expression of LC3 and Beclin-1 gene began to increased after the 6h reperfusion of I/R injury and peaked at 24h of reperfusion.Conclusion The expression level of NGAL increased at the early stage of renal I/R injury in rats,which was earlier than the changes of BU and SCr levels,and could be used as a molecular indicator for early diagnosis of renal I/R injury.During the aggravation of renal I/R injury,the expression of NGAL was increased and autophagy was activated,which indica-ted that NGAL and autophagy played a certain role in the process of renal I/R injury.

Correlation between serum KIM-1,NGAL and diabetic kidney disease remission after gastric bypass surgery in obese patients / 中国糖尿病杂志

Objective To investigate the correlation between serum renal injury molecule-1(KIM-1)and neutrophil gelatinase-associated lipocalin(NGAL)in the remission of diabetic kidney disease(DKD)after gastric bypass surgery in obese DKD patients.Methods Seventy-nine obese patients with DKD who received gastric bypass surgery in our hospital from January 2021 to January 2022 were selected and divided into DKD remission group(n= 47)and DKD non-remission group(n=32)according to whether UACR decreased to normal level after surgery.Preoperative and postoperative general data were collected and biochemical indices,serum KIM-1 and NGAL levels were detected.Results None of the 79 obese DKD patients had intraoperative complications or switched to laparotomy.BMI,FPG,HbA1c,SBP,DBP,TC,TG,LDL-C,SUA,UACR,KIM-1 and NGAL were decreased after surgery,while HDL-C was increased after surgery(P＜0.05).SBP,DBP,Scr,BUN,UACR,KIM-1 and NGAL in remission group were lower than those in non-remission group(P＜0.05).Spearman correlation analysis showed that the levels of KIM-1 and NGAL were positively correlated with Scr,BUN and UACR(P＜0.05),but negatively correlated with eGFR(P＜0.05).Logistic regression analysis showed that SBP,UACR,KIM-1 and NGAL were influencing factors for DKD remission after gastric bypass surgery.The areas under ROC curve of serum KIM-1,NGAL and combined prediction of DKD remission were 0.801,0.757 and 0.863,respectively.Conclusion Serum KIM-1 and NGAL can predict DKD remission in obese DKD patients after gastric bypass surgery.

A biomimetic liver cancer on-a-chip reveals a critical role of LIPOCALIN-2 in promoting hepatocellular carcinoma progression

Hepatic stellate cells (HSCs) represent a significant component of hepatocellular carcinoma (HCC) microenvironments which play a critical role in tumor progression and drug resistance. Tumor-on-a-chip technology has provided a powerful in vitro platform to investigate the crosstalk between activated HSCs and HCC cells by mimicking physiological architecture with precise spatiotemporal control. Here we developed a tri-cell culture microfluidic chip to evaluate the impact of HSCs on HCC progression. On-chip analysis revealed activated HSCs contributed to endothelial invasion, HCC drug resistance and natural killer (NK) cell exhaustion. Cytokine array and RNA sequencing analysis were combined to indicate the iron-binding protein LIPOCALIN-2 (LCN-2) as a key factor in remodeling tumor microenvironments in the HCC-on-a-chip. LCN-2 targeted therapy demonstrated robust anti-tumor effects both in vitro 3D biomimetic chip and in vivo mouse model, including angiogenesis inhibition, sorafenib sensitivity promotion and NK-cell cytotoxicity enhancement. Taken together, the microfluidic platform exhibited obvious advantages in mimicking functional characteristics of tumor microenvironments and developing targeted therapies.

Cerebrospinal fluid levels of sortilin-1, lipocalin-2, autotaxin, decorin and interleukin-33 in patients with idiopathic intracranial hypertension / Níveis de sortilina-1, lipocalina-2, autotaxina, decorina e interleucina-33 no líquido cefalorraquidiano em pacientes com hipertensão intracraniana idiopática

Abstract Background Idiopathic intracranial hypertension (IIH) is characterized by increased cerebrospinal fluid (CSF) pressure of unknown cause. It has been suggested that the inflammatory process plays a role in the pathophysiology of the disease. Sortilin-1, lipocalin-2, autotaxin, decorin, and interleukin-33 (IL-33) are among the factors involved in inflammatory processes. Objective To investigate the CSF levels of sortilin-1, lipocalin-2, autotaxin, decorin, and IL-33 in patients with IIH. Methods A total of 24 IIH patients and 21 healthy controls were included in the study. Demographic characteristics of the patients and of the control group as well as CSF pressures were evaluated. Sortilin-1, lipocalin-2, autotaxin, decorin and IL-33 levels in the CSF were measured. Results The CSF levels lipocalin-2, sortilin-1, autotaxin, IL-33 and CSF pressure were significantly higher in the patients group compared with the control group (p < 0.001). Decorin levels were reduced in patients (p < 0.05). There was no correlation between the autotaxin and IL-33 levels and age, gender, CSF pressure, and body mass index. The results of our study showed that inflammatory activation plays an important role in the development of the pathophysiology of IIH. In addition, the fact that the markers used in our study have never been studied in the etiopathogenesis of IIH is important in explaining the molecular mechanism of this disease. Conclusion Studies are needed to evaluate the role of these cytokines in the pathophysiology of the disease. It is necessary to evaluate the effects of these molecules on this process.

Resumo Antecedentes A hipertensão intracraniana idiopática (HII) é caracterizada pelo aumento da pressão do líquido cefalorraquidiano (LCR) de causa desconhecida. Tem sido sugerido que o processo inflamatório desempenha um papel na fisiopatologia da doença. Sortilina-1, lipocalina-2, autotaxina, decorina e interleucina-33 (IL-33) estão entre os fatores envolvidos nos processos inflamatórios. Objetivo Investigar os níveis de sortilina-1, lipocalina-2, autotaxina, decorina e IL-33 no LCR de pacientes com HII. Métodos Um total de 24 pacientes com HII e 21 controles saudáveis foram incluídos no estudo. Foram avaliadas as características demográficas dos pacientes e do grupo controle, bem como as pressões liquóricas. Os níveis de sortilina-1, lipocalina-2, autotaxina, decorina e IL-33 no LCR foram medidos. Resultados Os níveis no líquido cefalorraquidiano lipocalina-2, sortilina-1, autotaxina, IL-33 e pressão liquórica foram significativamente maiores no grupo de pacientes em comparação com o grupo controle (p < 0,001). Os níveis de decorina foram reduzidos nos pacientes (p < 0,05). Não houve correlação entre os níveis de autotaxina e IL-33 e idade, sexo, pressão liquórica e índice de massa corporal. Os resultados do nosso estudo mostraram que a ativação inflamatória desempenha um papel importante no desenvolvimento da fisiopatologia da HII. Além disso, o fato de os marcadores utilizados em nosso estudo nunca terem sido estudados na etiopatogenia da HII é importante para explicar o mecanismo molecular dessa doença. Conclusão Estudos são necessários para avaliar o papel dessas citocinas na fisiopatologia da doença. É necessário avaliar os efeitos dessas moléculas nesse processo

Normothermic machine perfusion of kidney and ischemia-free kidney transplantation / 器官移植

To increase the utilization rate of expanded criteria donor (ECD) kidney, the kidney preservation methods have been ever advancing in recent years. The application of normothermic machine perfusion (NMP) promotes the preservation, evaluation and repair of ex vivo donor kidneys and accelerates the innovation of surgical approaches of kidney transplantation. Ischemia-free kidney transplantation (IFKT), which initiated by Organ Transplantation Center of the First Affiliated Hospital of Sun Yat-sen University, keeps the blood flow and oxygen supply of the donor kidney with NMP machine during the entire process of acquisition, preservation and transplantation, thereby fundamentally avoiding ischemia-reperfusion injury (IRI) of the donor kidney and reducing the risk of delayed graft function (DGF) and acute rejection after surgery. In this article, recent progresses upon the kidney NMP, surgical procedures and short-term outcomes of IFKT were reviewed, aiming to provide reference for enhancing the utilization rate of ECD donor kidney and resolving the issue of organ shortage.

Predictive value of kidney injury markers for early DGF in kidney transplant recipients / 器官移植

Objective To evaluate the predictive values of serum neutrophil gelatinase-associated lipocalin (NGAL), urine NGAL, serum cystatin C (Cys-C) and serum creatinine (Scr) for early delayed graft function (DGF) in kidney transplant recipients. Methods Clinical data, blood and urine samples of 159 kidney transplant recipients were collected. All recipients were divided into the DGF group (n=42) and immediate graft function (IGF) group (n=117) according to the incidence of DGF. Clinical data of all recipients were analyzed. The changes of serum NGAL, urine NGAL, Cys-C and Scr levels were statistically compared between two groups. The predictive values of different markers for early DGF were assessed. Results Among 159 kidney transplant recipients, DGF occurred in 42 cases with an incidence rate of 26.4%. There were statistically significant differences in donor age, cold ischemia time of donor kidney and complement-dependent cytoxicity (CDC) between the two groups(all P < 0.05). Within postoperative 2 weeks, the serum NGAL levels in the DGF group were higher than those in the IGF group (all P < 0.05). The Cys-C, Scr and urine NGAL levels in the DGF group were higher compared with those in the IGF group within 3 weeks after kidney transplantation(all P < 0.001). Serum NGAL, urine NGAL, Cys-C and Scr levels had certain predictive values for early DGF in kidney transplant recipients. Cys-C yielded the highest predictive value with a cut-off value of 4.73 mg/L, sensitivity of 0.833, specificity of 0.812 and area under the curve (AUC) of 0.895. Conclusions Cys-C has higher predictive value for early DGF in kidney transplant recipients compared with serum NGAL, urine NGAL and Scr.

Inhibiting ferroptosis attenuates myocardial injury in septic mice: the role of lipocalin-2 / 南方医科大学学报

OBJECTIVE@#To explore the contribution of ferroptosis to myocardial injury in mouse models of sepsis and the role lipocalin-2 (Lcn2) in ferroptosis.@*METHODS@#Adult male C57BL/6 mice were randomized equally into sham-operated group, cecal ligation and puncture (CLP)-induced sepsis group, and CLP + Fer-1 group where the mice received intraperitoneal injection of 5 mg/mL Fer-1 (5 mg/kg) 1 h before CLP. The left ventricular functions (including LVEF%, LVFS%, LVIDd and LVIDs) of the mice were assessed by echocardiography at 24 h after CLP. Myocardial injury in the mice was observed with HE staining, and the changes of myocardial ultrastructure and mitochondria were observed using transmission electron microscopy (TEM). Serum TNF-α level was measured with ELISA, and the changes of myocardial iron content were detected using tissue iron kit. The protein expressions of myocardial Lcn2, glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) were determined with Western blotting.@*RESULTS@#The septic mice showed significantly decreased LVEF%, LVFS% and LVIDd and increased LVIDs at 24 h after CLP (P < 0.05), and these changes were significantly improved by Fer-1 treatment. Sepsis caused obvious myocardial pathologies and changes in myocardial ultrastructure and mitochondria, which were significantly improved by Fer-1 treatment. Fer-1 treatment also significantly ameliorated sepsis-induced elevations of serum TNF-α level, myocardial tissue iron content, and Lcn2 protein expression and the reduction of GPX4 and FSP1 protein expression levels (P < 0.05).@*CONCLUSION@#GPX4- and FSP1-mediated ferroptosis are involved in myocardial injury in mice with CLP-induced sepsis, and inhibition of ferroptosis can attenuate septic myocardial injury, in which Lcn2 may play a role.

Role of lipocalin-2 in the development and progression of liver diseases / 临床肝胆病杂志

Lipocalin-2 (LCN2) is a secreted glycoprotein originally purified from mouse kidney cells infected with simian virus 40 and plays a key role in the control of cellular homeostasis during inflammation and the response to cellular stress or injury, and it is considered a potential biomarker for rheumatic diseases, cancer, liver diseases, and inflammatory diseases. Studies have shown that LCN2 is expressed in hepatic parenchymal and nonparenchymal cells and is secreted into the bloodstream, and it is closely associated with the development and progression of acute liver injury, liver cirrhosis, viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma. This article summarizes the animal experiments and clinical studies on the association of LCN2 with the pathogenesis of liver diseases, in order to provide new ideas and therapeutic targets for the prevention and treatment of liver diseases.

Value of urine IL-8, NGAL and KIM-1 for the early diagnosis of acute kidney injury in patients with ureteroscopic lithotripsy related urosepsis / 中华创伤杂志(英文版)

PURPOSE@#To investigate the clinical value of urine interleukin-18 (IL-8), neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for the early diagnosis of acute kidney injury (AKI) in patients with ureteroscopic lithotripsy (URL) related urosepsis.@*METHODS@#A retrospective study was carried out in 157 patients with urosepsis after URL. The patients were divided into AKI group and non-AKI group according to the Kidigo guideline and urine IL-8, NGAL and KIM-1 levels were detected by enzyme-linked immunosorbent assay at 0, 4, 12, 24 and 48 h after the surgery. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of these three biomarkers for postoperative AKI.@*RESULTS@#The level of urine IL-8, NGAL and KIM-1 in AKI group was significantly higher than that in non-AKI group at 4, 12, 24 and 48 h (p < 0.01). The ROC analysis showed the combined detection of urine IL-8, NGAL and KIM-1 at 12 h had a larger area under curve (AUC) than a single marker (0.997, 95% CI: 0.991-0.998), and the sensitivity and specificity were 98.2% and 96.7%, respectively. Pearson correlation analysis showed that the levels of urine NGAL at 4, 12, 24 and 48 h in AKI patients were positively correlated with the levels of urine KIM-1 and IL-18 (p < 0.01).@*CONCLUSION@#AKI could be quickly recognized by the elevated level of urine IL-8, NGAL and KIM-1 in patients with URL-related urosepsis. Combined detection of the three urine biomarkers at 12 h after surgery had a better diagnostic performance, which may be an important reference for the early diagnosis of AKI.

Correlation between serum lipocalin-2 and white matter hyperintensities in patients with ischemic stroke / 国际脑血管病杂志

Objective:To investigate the correlation between the lipocalin-2 (LCN-2) level and white matter hyperintensities (WMHs) in patients with ischemic stroke.Methods:Consecutive patients with ischemic stroke admitted to the Department of Neurology, Jinling Hospital, Medical School of Nanjing University from September 2021 to November 2021 and whose duration from onset to hospitalization <14 d were prospectively enrolled. Enzyme-linked immunosorbent assay was used to detect the serum LCN-2. Fazekas scale was used to assess the severity of periventricular and subcortical WMHs. A total WMHs score ≥3 was defined as severe WMHs. Multivariate logistic regression analysis was used to determine the correlation between serum LCN-2 level and WMHs. Results:A total of 179 patients were enrolled, including 122 males (68.2%), aged 64.7±11.6 years. The median serum LCN-2 level was 387.1 g/L, and 86 patients (48.0%) had severe WMHs. Serum LCN-2 in the severe WMH group was significantly higher than that in the non-severe WMH group (505.3±342.4 g/L vs. 367.8±224.5 g/L; t=3.110, P=0.002). Multivariable logistic regression analysis showed that after adjusting for the relevant confounding factors, there was a significant correlation between higher serum LCN-2 and severe WMHs (odds ratio 2.32, 95% confidence interval 1.17-4.63; P=0.017) and higher total WMHs score (odds ratio 1.62, 95% confidence interval 1.12-2.35; P=0.011). Conclusion:Higher serum LCN-2 level is associated with severe WMHs in patients with ischemic stroke.

Detective value of placental tissue resistin, human lipid carrier protein and blood glucose and lipid metabolism in gdm patients complicated with preeclampsia / 中华内分泌外科杂志

Objective:To analyze the detective value of placental tissue resistin, human lipid carrier protein (LCN) and blood glucose and lipid metabolism in pregnant women with gestational diabetes mellitus (GDM) complicated with preeclampsia (PE) , providing guidance for the early treatment of GDM complicated with preeclampsia.Methods:96 pregnant women with GDM complicated with PE (GDM-PE group) admitted to Yantai Yantaishan Hospital from Jan. 2017 to Jan. 2020 were selected and retrospectively studied. According to the ratio of 2:1, the pure GDM pregnant women (GDM group) and 48 normal pregnant women (the control group) were selected. The placenta tissue resistin and LCN levels were determined by immunohistochemistry. Blood samples were collected to determine the glucose and lipid metabolism. The pregnancy outcomes of each group were compared and the relationship between resistin, LCN, glucose and lipid metabolism and GDM complicated with PE was analyzed.Results:Fasting blood-glucose (FBG) was (4.57±0.66) mmol/L in GDM group and (5.23±0.61) mmol/L in GMD-PE group. FINS (11.97±1.5) mIU/L, (15.12±3.52) mIU/L were higher than those of control group (4.11±0.23) mmol/L, (6.75±1.34) mIU/L ( P<0.05) . FBG, FINS, glycosylated hemoglobin (HbA1c) in GDM-PE group were higher than those in GDM group. TC) (6.71±1.63) mmol/L, triglyceride, TG (6.59±0.87) mmol/L was higher than that of control group (5.87±0.73) mmol/L, (4.57±0.59) mmol/L and GDM group (6.02±1.55) mmol/L, (4.71±0.63) mmol/L ( P<0.05) . high density lipoprotein cholesterol (HDL-C) (1.21±0.34) was lower than that of control group (1.54±0.39) and GDM group (1.55±0.43) ( P<0.05) . The positive rates of resistin 85.42%, 60.42%, LCN 81.25%, 56.25% in GDM-PE group and GDM group were higher than those in control group 39.58%, 31.25% ( χ2=32.096, 4.167; 34.975, 6.095, both P<0.05) . The positive rates of resistin and LCN in GDM-PE group were higher than those in GDM group ( χ2=11.322, 11.257, both P<0.01) . The gestational age of delivery in GDM-PE group was (37.11±2.06) weeks earlier than that in GDM group (38.21±1.75) weeks and control group (38.36±1.42) weeks ( F=9.836, P<0.05) . The birth weight of neonates (2 905.45±356.79) g was lower than that of control group (3 321.52±366.46) g and GDM group (3 425.14±269.87) g ( F=46.606, P<0.05) . Postpartum blood loss (415.34±126.75) ml was significantly higher than that of GDM group (338.65±105.63) ml and control group (298.42±75.26) ml ( F=19.932, P<0.05) . The preterm birth rate of 20.83% was higher than that of the GDM group (8.33%) and the control group (4.17%) ( χ2=9.075, P<0.05) . The postpartum blood loss of the GDM group was higher than that of the control group ( t=-2.148, P<0.05) . The incidences of fetal distress, premature rupture of membranes, fetal growth restriction and postpartum hemorrhage in GDM-PE group were higher than those in control group ( χ2=4.571, 6.867, 5.941, 5.123, P<0.05) . The protein expressions of resistin and LCN in placenta of pregnant women with GDM-PE were positively correlated with FBG, FINS, TC and TG ( r=0.517, 0.463, 0.559, 0.521, 0.485, 0.497, 0.557, 0.571, P<0.05) . Was negatively correlated with HDL-C ( r=-0.317, -0.357, P<0.05) . Conclusions:The positive rate of resistin and LCN in the placenta tissue of pregnant women with GDM complicated with PE is higher than that of GDM and normal pregnant women, their disorder of glucose and lipid metabolism is more obvious, and the incidence of adverse maternal and infant outcomes is higher. It is speculated that resistin and LCN may synergistically affect the metabolism of glucose and lipids causing adverse pregnancy outcomes in GDM complicated with PE.

Effects and significance of continuous hemoperfusion on patients with diquat poisoning / 中华危重病急救医学

Objective:To investigate the effect of continuous hemoperfusion (HP) on the levels of soluble CD14 isoform (sCD14-st) and neutrophil gelatinase-associated lipocalin (NGAL) on patients with diquat (DQ) poisoning and its significance.Methods:A total of 86 patients with acute DQ poisoning admitted to the department of emergency medicine, Harrison International Peace Hospital Affiliated to Hebei Medical University from May 2018 to August 2021 were enrolled and divided into the intermittent HP group (40 cases) and the continuous HP group (46 cases) according to the random number table method. All patients received basic treatment and continuous veno-venous hemofiltration (CVVH) within 24 hours after admission. On this basis, the intermittent HP group received HP treatment within 2 hours, lasting 2 hours each time for every 8 hours, 3 times in all; the continuous HP group received continued HP treatment until there was no DQ component in urine samples. Serum NGAL levels were detected in all patients before treatment and at 3 hours, 12 hours, 24 hours, 2 days, 3 days, 5 days, and 7 days after treatment. At the same time, serum sCD14-st, blood lactate (Lac), arterial partial pressure of oxygen (PaO 2), serum creatinine (SCr), MB isoenzyme of creatine kinase (CK-MB) and interleukin-18 (IL-18) levels were detected before treatment and at 24 hours, 3 days, and 7 days after treatment. Kaplan-Meier survival curve was drawn to analyze the 28-day survival of patients. Results:Before treatment, there was no significant difference in serum NGAL, sCD14-st, Lac, PaO 2, SCr, CK-MB and IL-18 levels between the two groups. With the prolongation of treatment, the serum levels of NGAL, sCD14-st, Lac, SCr, CK-MB and IL-18 in the intermittent HP group increased at first and then decreased. Serum levels of NGAL, sCD14-st, CK-MB and IL-18 reached their peaks at 24 hours after treatment, and the Lac and SCr levels reached their peaks at 3 days after treatment. In addition, the levels of the above indexes at each time point in the continuous HP group were all significantly lower than those in the intermittent HP group [after 24 hours of treatment: NGAL (μg/L) was 345.90±30.75 vs. 404.24±38.79, sCD14-st (ng/L) was 1 941.88±298.02 vs. 2 656.35±347.93, CK-MB (U/L) was 30.67±9.11 vs. 43.28±8.06, IL-18 (ng/L) was 139.49±16.29 vs. 177.98±27.85; 3 days of treatment: Lac (mmol/L) was 2.98±0.26 vs. 3.72±0.49, SCr (μmol/L) was 125.01±24.24 vs. 156.74±28.88; all P < 0.05]. However, there was no significant difference in PaO 2 levels between the two groups at each time point after treatment. The Kaplan-Meier survival curve showed that the 28-day mortality of patients in the continuous HP group was significantly lower than that in the intermittent HP group [26.09% (12/46) vs. 52.50% (21/40); Log-Rank test: χ2 = 7.288, P = 0.007]. Conclusion:Continuous HP could effectively reduce serum sCD14-st, NGAL levels and 28-day mortality in patients with DQ poisoning, with good curative effect.