Primary focal and segmental glomerulosclerosis and soluble factor urokinase-type plasminogen activator receptor

Primary focal and segmental glomerulosclerosis(FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The different available therapeutic approaches are unsuccessful, in part due to partially deciphered heterogeneous and complex pathophysiological mechanisms. Moreover, the term FSGS, even in its primary form, comprises a histological description shared by a number of different causes with completely different molecular pathways of disease. This review focuses on the latest developments regarding the pathophysiology of primary acquired FSGS caused by soluble factor urokinase type plasminogen activator receptor, a circulating permeability factor involved in proteinuria and edema formation, and describes recent advances with potential success in therapy.

Urokinase-type plasminogen activator receptor as a predictor of poor outcome in patients with systemic inflammatory response syndrome

BACKGROUND:Urokinase-type plasminogen activator(uPA) and urokinase-type plasminogen activator receptor(uPAR) are known as important factors,which mediate a variety of functions in terms of vascular homeostasis,inflammation and tissue repair.However,their role in systemic inflammatory response syndrome(SIRS) has been less well studied.This study aimed to test the hypothesis that the abnormalities of fibrinolysis and degradation of extracellular matrix mediated by uPA and uPAR are directly related to the patients with SIRS.We therefore analyzed their role and clinicopathological significance in patients with SIRS.METHODS:A case-control study was conducted with 85 patients who were divided into two groups according to the diagnostic criteria of SIRS:SIRS group(n=50) and non-SIRS group(/7=35).The SIRS group was divided into MODS group(n=26) and non-MODS group(n=24) by their severity,and survival group(n=35) and non-survival group(n=15) by their prognosis.Another 30 healthy adults served as normal controls.uPA and uPAR in plasma were detected by commercial enzyme-linked immunosorbent assay(ELISA) kits.RESULTS:The plasma level of uPA was lower in the SIRS group than in the non-SIRS group and controls(P<0.001 and P<0.001).It was lower in sepsis patients and the MODS group than in the non-sepsis patients and the non-MODS patients(all P<0.05).However,there was no difference in uPA level between survivors and non-survivors(P>0.05).The plasma level of uPAR increased in the SIRS group compared with the non-SIRS group and controls(P<0.001 and P<0.001).There was a significant elevation of uPAR in sepsis patients,MODS patients and non-survivors as compared with non-sepsis patients,non-MODS patients and survivors respectively(all P<0.05).Plasma uPAR levels were positively correlated with APACHE Ⅱ score(r=0.575,P<0.001) and SOFA score(r=0.349,P=0.013).AUCs for the prediction of SIRS mortality were 0.67 and 0.51,respectively,for uPA and uPAR.CONCLUSION:uPAR could be a predictor of poor outcome in patients with SIRS.

Relationship between matrix metalloproteinase-2 mRNA expression and clinicopathological and urokinase-type plasminogen activator system parameters and prognosis in human gastric cancer

AIM: To investigate the relationship between matrix metalloproteinase-2 (MMP-2) mRNA expression and clinicopathologic and urokinase-type plasminogen activator (uPA) system parameter and prognosis in human gastric cancer.METHODS: Expression of MMP-2 mRNA, uPA, and uPA-R mRNA in tumor tissues and ≥5 cm adjacent normal tissues from 67 cases of gastric cancer was studied using RTPCR and Northern blot respectively. Survival analyses were done using the Kaplan-Meier method. RESULTS: The expression rates of MMP-2 mRNA, uPA and uPA-R mRNA in tumor tissues (31%, 41%, and 51%, respectively) were significantly higher than those in ≥5 cm adjacent tissues (19%, 11%, and 9%; χ2 = 4.59, 43.58, and 53.24 respectively, P＜0.05, 0.0001, and 0.0001, respectively). Expression of MMP-2 mRNA was significantly correlated with lymph node metastasis (metastasis:61.9%, no metastasis: 39.1%, χ2= 7.61, P＜0.05), Lauren's classification of diffuse/mixed types: 54.2%, intestinal type: 26.3%, χ2 = 4.25, P＜0.05, expression of uPA and uPA-R mRNA (uPA+: 55.1%, uPA-: 22.2% and uPA-R+: 54.9%, uPA-R-: 18.8%, x2= 5.72 and 6.40 respectively, P＜0.05). Kaplan-Meier survival analysis of MMP-2 mRNA expression did not show significant difference in all 67 cases, but revealed an association of the expression of MMP-2 mRNA, uPA, and uPA-R mRNA with worse prognosis (P = 0.0083, 0.0160, and 0.0094, respectively). CONCLUSION: MMP-2 may play an important role in the development of invasion and metastasis of gastric cancer.

Gene expression changes of urokinase plasminogen activator and urokinase receptor in rat testes at postnatal stages

Aim： To investigate the gene expression changes of urokinase plasminogen activator （uPA）/urokinase receptor （uPAR） in rat testes at postnatal stages and explore the effects of uPA/uPAR system on the rat spermatogenesis. Methods： The mRNAs of uPA and uPAR in rat testes were measured by using real-time quantitative polymerase chain reaction （PCR） at postnatal days 0, 5, 10, 15, 21, 28, 35, 42, 49 and 56, respectively. Results： The tendencies of uPA and uPAR mRNA expression were similar at most postnatal stages except for Do. The expression of uPAR mRNA in rats testes was relatively higher than that of uPA at postnatal Do, and both were decreased until D21, increased obviously at postnatal D28, reached a peak at postnatal D35, then declined sharply at postnatal D42 and retained at a low level afterwards. Conclusion： The uPA/uPAR system may be strongly linked to spermiation and spermatogenesis via regulating germ cell migration and proliferation, as well as promoting the spermiation and detached residual bodies from the mature spermatids.

THE INCREASE IN PLASMINOGEN ACTIVATOR INHIBITOR TYPE-1 EXPRESSION BY STIMULATION OF ACTIVATORS FOR PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS IN HUMAN ENDOTHELIAL CELLS

Objective.To investigate the effect of peroxis ome proliferator-activated recept ors(PPARs )activators on plasminogen activator inhibitor ty pe-1(PAI-1)expression in human umbilical vein e ndothelial cells and the possi-ble mechanism.Methods.Human umbilical vein endothelial ce lls(HUVECs )were obtained from normal fetus,and cul-tured conventionally.Then the HUVECs were exposed to test agents(linolenic acid,linoleic acid,oleic acid,stearic acid and prostaglandin J 2 respectively)in varying concentrations with fresh media.RT -PCR and ELISA were applied to determine the expression of PPARs and PAI-1in HUVECs.Results.PPARα,PPARδand PPARγmRNA were detected by using RT-PCR in HUVECs.Treatment of HUVECs with PPARαand PPARγactivators---linolenic acid,linoleic acid,oleic acid and prostaglandin J 2 respectively,but not with stearic a cid could augment PAI-I mRNA expression and protein secretion in a concentration-dependent manner.However,the mRNA expressions of 3subclasses of PPAR with their activators in HUVECs were not changed compared w ith controls.Conclusion.HUVECs express PPARs.PPARs activators may increase PAI-1expression in ECs,but the underlying mechanism remains uncle ar.Although PPARs expression was not enhanced after stimulated by their activators in ECs,the role of functionally active PPARs in regulating PA I-1expression in ECs needs to be further investigated by using transient gen e transfection assay.

Elevation of serum urokinase plasminogen activator receptor and liver stiffness in postoperative biliary atresia

AIM To investigate serum urokinase-type plasminogen activator receptor(u PAR) and liver stiffness in biliary atresia(BA) and examine the correlation of circulating u PAR, liver stiffness, and clinical outcomes in postoperative BA children.METHODS Eighty-five post Kasai BA children and 24 control subjects were registered. Circulating u PAR was measured using enzyme-linked immunosorbent essay. Liver stiffness was analyzed using transient elastography.RESULTS BA children had significantly greater circulating u PAR andliver stiffness scores than control subjects(P < 0.001). Circulating u PAR and liver stiffness were substantially higher in jaundiced BA children than non-jaundiced BA children(P < 0.001). In addition, circulating u PAR was positively associated with serum aspartate aminotransferase(r = 0.507, P < 0.001), alanine aminotransferase(r = 0.364, P < 0.001), total bilirubin(r = 0.559, P < 0.001), alkaline phosphatase(r = 0.325, P < 0.001), and liver stiffness scores(r = 0.508, P < 0.001).CONCLUSION Circulating u PAR and liver stiffness values were greater in BA children than healthy controls. The increased circulating u PAR was associated with liver dysfunction in BA. As a consequence, serum u PAR and liver stiffness may be used as noninvasive biomarkers indicating the progression of liver fibrosis in post Kasai BA.

Crystal Structures of 2-Aminobenzothiazole-based Inhibitors in Complexes with Urokinase-type Plasminogen Activator

Urokinase-type plasminogen activator （uPA） plays a crucial role in the regulation of plasminogen activation, tumor cell adhesion and migration. The inhibition of uPA activity is a promising mechanism for anti-cancer therapy. Most current uPA inhibitors employ a highly basic group （either amidine or guanidine group） to target the S1 pocket of uPA active site, which leads to poor oral bioavailability. Here we study the possibility of using less basic 2-aminobenzothiazole （ABT） as S1 pocket binding group. We report the crystal structures of uPA complexes with ABT or 2-amino-benzothiazole-6-carboxylic acid ethyl ester （ABTCE）. The inhibitory constants of these two inhibitors were measured by a chromogenic competitive assay, and it was found that ABTCE is a better inhibitor for uPA （Ki = 656 μM） than ABT （Ki = 5.03 mM）. This work shows that 2-amniobenzothiazole can be used as P1 group which may have better oral bioavailability than the commonly used amidine or guanidine group. We also found the ethyl ester group occupies the characteristic oxyanion hole and contacts to uPA 37- and 60-loops. Such work provides structural information for further improvements of potency and selectivity of this new class of uPA inhibitor.

Elevated Plasma Tissue-type Plasminogen Activator (t-PA) and Soluble Throm-bomodulin in Patients Suffering From Severe Acute Respiratory Syndrome (SARS) as a Possible Index for Prognosis and Treatment Strategy

To detect the presence of endothelial injury in patients with severe acute respiratory syndrome （SARS） via enhanced levels of tissue-type plasminogen activator （t-PA） and soluble thrombomodulin （sTM）. Methods Case patients were from Xuanwu Hospital （Capital University of Medical Sciences, Beijing, China）, and all of them met clinical criteria for SARS. Healthy controls were some of the hospital employees. Endothelial injury bio-markers tPA and sTM were detected by commercial ELISA-methods. Results Classic plasma markers of endothelial injury, tPA and sTM significantly elevated in SARS patients in comparison to controls [t-PA： 1.48±0.16 nmol/L versus 0.25±0.03 nmol/L （P〈0.0001）, and sTM： 0.26±0.06 nmol/L versus 0.14±0.02 nmol/L （P〈0.05）]. The only patient who died had extremely high levels of these endothelial injury markers （t-PA： 2.77 nmol/L and sTM： 1.01 nmol/L）. The likelihood ratio analysis indicated the excellent discriminating power for SARS at the optimal cut-point of 0.49 nmol/L for tPA and 0.20 nmol/L for sTM, respectively. Significant numerical correlations were found among these endothelial injury markers in SARS patients. The numerical coefficient of correlation Pearson r between t-PA and sTM was 0.5867 （P〈0.05）. Conclusion Increased plasma concentrations of tPA and sTM in patients with SARS suggest the possibility of endothelial injury. SARS patients might need anticoagulant therapy or fibrinolytic therapy in order to reverse intraalveolar coagulation, microthrombi formation, alveolar and interstitial fibrin deposition. It may not only provide a useful treatment and prognostic index but also allow a further understanding of the pathological condition of the disease.

Role of Urokinase-type Plasminogen Activator in the Precontact Sperm-egg Communication and Fertility of Mice in vitro

Objective To explore the role of urokinase-type plasminogen activator（uPA） in precontact sperm-egg communication and fertility of mice in vitro. Methods Firstly, sperm chemotaxis （SC） induced by uPA was assayed by measuring the sperm densities in capillaries with a descending gradient or no gradient of uPA respectively. Secondly, the role of uPAR that exists in sperm plasma membrane in SC was studied by examining the change of sperm density in capillary after incubating spermatozoa with anti-uPAR antibody. Thirdly, SC induced by eggs, which had been treated with uPA, PAl-1 and anti-uPAR beforehand respectively, was assayed to study the role of uPA in PSEC. Lastly, the fertilization capability of spermatozoa treated with uPA was examined by counting the number of fertilized eggs. Results 1）The density of spermatozoa that migrated down the gradient of uPA into the capillary was significantly lower than that into the capillary containing no-gradient uPA. 2） When uPAR of spermatozoa was inhibited by anti-uPAR antibody, the density of spermatozoa that migrated into the capillary with ascending gradient of uPA decreased correspondingly. 3） The density of spermatozoa attracted by eggs, which were treated with uPA beforehand, increased significantly than that of attracted by non-treated eggs. On the contrary, the sperm density decreased correspondingly when the egg was treated with PAI-1. 4） The number of fertilized eggs increased significantly after the spermatozoa used here was treated with uPA beforehand. Conclusion uPA could induce SC of mice sperm in vitro through the uPAR on its membrane, enhance the capability of egg inducing SC, and promote spermatozoa to fertilize eggs. Thus, uPA may act as an attractant in PSEC, increase the chance encounter of spermatozoa and eggs, therefore, enhance the fertility success correspondingly. This study, in some degree, provides an evidence that uPA may be used as a new medicine and diagnostic reagent for male infertility.

Bone Marrow Urokinase Plasminogen Activator Receptor Levels are Associated with the Progress of Multiple Myeloma

Objective To determine the mRNA and protein levels of urokinase plasminogen activator receptors(u PAR) in bone marrow fluid and bone marrow tissue from multiple myeloma(MM) patients and assess association of u PAR level with prognosis of MM.Methods u PAR levels in bone marrow fluid of 22 MM patients at the stable and progressive stages and 18 iron deficiency anemia patients with normal bone marrow(control) were examined by ELISA.Furthermore,u PAR expression in bone marrow tissue was investigated by RT-PCR and Western blot,respectively.The distribution of u PAR in MM cells was examined using immunofluorescence staining.The pathological changes in different stages of MM patients were studied by HE staining.Results u PAR level in bone marrow fluid of MM patients(1.52±0.32 μg/ml) was found to be higher than that in the control group(0.98±0.15 μg/ml).Interestingly,u PAR protein(0.686±0.075 vs.0.372±0.043,P<0.05) and m RNA(2.51±0.46 vs.4.46±1.15,P<0.05) expression levels of MM patients at the progressive stage were significantly higher than those at the stable stage.The expression of u PAR in MM bone marrow was confirmed by immunofluorescence staining.Moreover,HE staining revealed a great increased number of nucleated cells and severe impairment of hematopoietic function in the bone marrow of patients with progressive-stage myeloma.Conclusion Our study reveals that u PAR expression is positively correlated with the development and progress of MM.

EXPRESSION AND SIGNIFICANCE OF UROKINASE-TYPEPLASMINOGEN ACTIVATOR IN BREAST CANCER

Objective: To study the expression and clinical significance of urokinase-type plasminogen activator (uPA) in breast cancer. Methods: Applying streptavidin-biotin complex (SABC) immunohistochemical technique, expression of uPA was studied in 100 patients with primary breast cancer. Results: There were 55 patients with high uPA expression, and 45 with lower expression. There was significant correlation between uPA expression and TNM stage, lymph node status, and the tumor size. Neither age, menopausal status, nor ER status was significantly related with level of uPA expression. The patients with high expression of uPA had significantly shorter disease-free survival (DFS) and overall survival (OS) than did those with low expression of uPA. Univariate analysis showed that uPA as a prognostic factor was of similar magnitude to lymph node status and TNM stage, but stronger than that of ER status and tumor size. UPA was an independent prognostic factor affecting disease-free survival and overall survival. Conclusion: uPA appears to be a strong and independent biologic marker for predicting prognosis of breast cancer.

Crystal Structures of Urokinase-type Plasminogen Activator in Complex with 4-(Aminomethyl) Benzoic Acid and 4-(Aminomethyl-phenyl)-methanol

Urokinase-type plasminogen activator （uPA） is a trypsin-like serine protease and plays a key role in several biological processes, including tissue remodeling, cell migration, and matrix degradation. The inhibitors of uPA have been shown to prevent the spread of metastasis and tumor growth, and accordingly uPA is widely recognized as a target for the treatment of cancer. In this work, we report the crystal structures of the complexes of uPA with its inhibitors： 4- （aminomethyl）-benzoic acid （AMBA） and 4-（aminomethyl-phenyl）-methanol （AMPM）, both at a resolution of 2.35 А. The inhibitory constants of these two inhibitors were measured by a chromogenic competitive assay, and it was found that AMBA is a better inhibitor for uPA （Ki = 2.68 mM） than AMPM （Ki = 13.99 mM）. The structural study shows that the binding mode of inhibitor AMBA on uPA is similar to that of AMPM on uPA, both docked into the active site S1 pocket of uPA. Structural details of these complexes are provided to explain the difference of inhibitory constants.

儿童慢性肾脏疾病早期诊断的生物标志物研究进展

血清肌酐和蛋白尿作为慢性肾脏疾病(CKD)进展的生物标志物,其地位已毋庸置疑,但其不能涵盖一些其他类型的病变。最近的研究发现了反映CKD不同方面的生物标志物,这些标志物可以提供CKD进展风险和相关不良预后的信息。该综述重点介绍了儿童CKD早期诊断的一些生物标志物,包括血浆肾损伤分子-1、成骨细胞生长因子23、肿瘤坏死因子受体-1、肿瘤坏死因子受体-2、可溶性尿激酶浆细胞激活剂受体和人软骨糖蛋白,以及尿液表皮生长因子、α-1微球蛋白、肾损伤分子-1和人软骨糖蛋白。研究发现,即使在调整了血清肌酐或估计的肾小球滤过率和蛋白尿后,这些血浆和尿液生物标志物在CKD患儿中的水平仍较高,也与CKD进展独立相关。这些新的生物标志物代表了肾小管损伤、肾小管功能障碍、炎症和肾小管健康的不同生物途径,可以作为液体活检来更好地描述儿童CKD的疾病特征。新型的血液和尿液生物标志物提高了临床医师对CKD进展的预后评估能力,并可能提高对CKD病理生理学的认识。但对于与CKD结局相关的临床前生物标志物,其在研究队列和设计之间存在相当大的异质性,限制了不同研究之间预后表现的比较。需要更大规模的临床研究来确定这些生物标志物如何在临床中使用,以改善CKD的临床管理。

血清肾胺酶、尿调节素、可溶性尿激酶受体联合检测对糖尿病肾损伤早期诊断的价值分析

目的探究血清肾胺酶(RNLS)、尿调节素(UMOD)、可溶性尿激酶型纤溶酶原激活物受体(suPAR)联合检测对糖尿病肾损伤早期诊断的价值。方法选取2020年3月至2021年3月成都市第七人民医院收治的61例糖尿病肾损伤病人为糖尿病肾损伤组,按24 h尿白蛋白排泄率(UAER)分为早期糖尿病肾病组(29例)和临床期糖尿病肾病组(32例),选取66例糖尿病病人为单纯糖尿病组,另选取同期健康体检者60例为对照组。收集病人的一般临床资料并比较,采用尿素酶法检测血清尿素(UREA),氧化酶法检测肌酐(Cr)和尿酸(UA)水平,采用酶联免疫吸附法(ELISA)检测血清RNLS、UMOD、suPAR的水平。Pearson相关性分析RNLS、UMOD、suPAR与UREA、Cr、UA以及临床资料的关系。采用受试者操作特征(ROC)曲线分析血清RNLS、UMOD、suPAR联合检测对糖尿病病人发生肾损伤的诊断价值。结果糖尿病肾损伤组、单纯糖尿病组三酰甘油、总胆固醇、空腹血糖、糖化血红蛋白及血清UREA、Cr、UA、suPAR水平[(133.56±42.68)ng/L,(66.48±17.13)ng/L比(34.15±8.26)ng/L]均显著高于对照组(P<0.05),估算肾小球滤过率(eGFR)及血清RNLS[(28.62±7.61)mg/L,(35.47±9.29)mg/L比(42.81±13.24)mg/L]、UMOD水平[(64.28±16.82)g/L,(119.45±28.65)g/L比(139.82±32.84)g/L]均显著低于对照组(P<0.05);且糖尿病肾损伤组较单纯糖尿病组升高或下降幅度大(P<0.05)。糖尿病肾损伤组糖尿病病程显著高于单纯糖尿病组(P<0.05),24 h尿蛋白显著高于单纯糖尿病组和对照组(P<0.05)。临床期糖尿病肾病组病人血清RNLS[(26.28±6.69)mg/L比(31.18±8.34)mg/L]、UMOD水平[(51.26±14.41)g/L比(78.65±19.49)g/L]较早期糖尿病肾病组均显著降低(P<0.05),suPAR水平[(151.96±48.03)ng/L比(113.27±36.81)ng/L]显著升高(P<0.05)。RNLS、UMOD与UREA、Cr、UA、三酰甘油、总胆固醇、空腹血糖、糖化血红蛋白、糖尿病病程及24 h尿蛋白均呈负相关(P<0.05),与eGFR呈正相关(P<0.05);suPAR与UREA、Cr、UA、三酰甘油、总胆固醇、空腹血糖、糖化血红蛋白、糖尿病病程及24 h尿蛋白均呈正相关(P<0.05),与eGFR呈负相关(P<0.05)。ROC曲线分析结果显示,血清RNLS、UMOD、suPAR三项联合的曲线下面积(AUC)0.88显著高于RNLS、UMOD单项检测的AUC(0.81、0.83)(P<0.05),而与suPAR AUC比较差异无统计学意义(P>0.05)。结论糖尿病肾损伤病人血清RNLS、UMOD、suPAR水平呈异常表达,且三项联合检测对糖尿病病人发生肾损伤的诊断价值较高,值得临床推广应用。

利伐沙班对氧化型低密度脂蛋白诱导的人脐静脉内皮细胞功能的影响

目的探讨利伐沙班(RIV)对氧化型低密度脂蛋白(Ox-LDL)诱导的人脐静脉内皮细胞(HUVEC)功能损伤的影响。方法根据干预措施,将实验分为空白对照组(A组,常规培养液),Ox-LDL组(B组,100μg/mL Ox-LDL的培养液),Ox-LDL+RIV125组(C1组,100μg/mL Ox-LDL和125 ng/mL RIV的培养液),Ox-LDL+RIV250组(C2组,100μg/mL Ox-LDL和250 ng/mL RIV的培养液)和Ox-LDL+RIV500组(C3组,100μg/mL Ox-LDL和500 ng/mLRIV的培养液),各组细胞均处理48 h。采用CCK-8法检测各组细胞存活率的变化,采用流式细胞术检测细胞凋亡情况,采用酶联免疫吸附试验(ELISA)检测白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、肿瘤坏死因子-α(TNF-α)水平,采用免疫印迹(Western blot)法检测细胞核因子-κB(NF-κB)和尿激酶型纤溶酶原激活因子受体(uPAR)蛋白表达水平。结果与B组比较,C1组、C2组、C3组细胞存活率显著升高(P<0.05),细胞凋亡率和uPAR表达水平均显著降低(P<0.05);C3组IL-1β,TNF-α,IL-6水平和p-NF-κB p65表达水平显著降低(P<0.05)。结论RIV能显著恢复细胞活力、减少细胞凋亡和由Ox-LDL引起的炎性反应,可能通过NF-κB和uPAR的调节而发挥作用。

预后营养指数及血清suPAR、TK1在晚期肝癌预后中的预测价值

目的探索预后营养指数(PNI)及血清可溶性尿激酶型纤溶酶原激活物受体(suPAR)、胸苷激酶1(TK1)在晚期肝癌表达意义以及在预后评估中预测的应用价值。方法选取2019年2月至2021年2月收集的92例晚期肝癌患者进行回顾性分析,均进行PNI评估及血清suPAR、TK1检测,比较两组PNI、suPAR、TK1水平。同时,根据患者是否死亡,分为预后不良组(n=28,死亡),预后良好组(n=64,生存),经多因素Cox回归模型分析影响晚期肝癌患者预后独立危险因素,经受试者操作特征(ROC)曲线分析PNI、suPAR、TK1的诊断价值。结果经单因素分析,血管侵犯、门静脉癌栓会对晚期肝癌预后造成影响(P<0.05),且预后不良组PNI低于预后良好组,suPAR、TK1水平高于预后良好组,差异有统计学意义。Kaplan-Meier生存分析显示,PNI高表达、suPAR低表达、TK1低表达、无血管侵犯、无门静脉癌栓者生存时间显著高于PNI低表达、suPAR高表达、TK1高表达、有血管侵犯、有门静脉癌栓者,差异有统计学意义(P<0.05);经多因素Cox回归模型分析,PNI低表达、suPAR高表达、TK1高表达是影响晚期肝癌患者预后的独立危险因素(P<0.05)。经ROC曲线分析,PNI、suPAR、TK1及3项联合诊断晚期肝癌预后的曲线下面积分别为0.818、0.827、0.801、0.957。结论晚期肝癌患者血清suPAR、TK1水平升高,PNI降低,PNI、suPAR、TK1可作为一项简捷而有效的指标,来协助评估晚期肝癌患者的病情严重程度及预后。

血清eCIRP、suPAR预测脓毒症致急性呼吸窘迫综合征患者预后的价值分析

目的探讨血清细胞外冷诱导RNA结合蛋白(eCIRP)、可溶性尿激酶纤溶酶原激活物受体(suPAR)预测脓毒症致急性呼吸窘迫综合征(ARDS)患者预后的价值。方法选取2019年1月—2023年6月上海交通大学医学院附属第九人民医院急诊科收治的脓毒症致ARDS患者84例(ARDS组),按照1∶1比例选取单纯脓毒症患者84例(非ARDS组),根据预后将脓毒症致ARDS患者分为死亡亚组(37例)和存活亚组(47例)。采用酶联免疫吸附法检测血清eCIRP、suPAR水平。通过多因素Logistic回归和受试者工作特征(ROC)曲线分析脓毒症致ARDS患者死亡的因素及血清eCIRP、suPAR水平预测价值。结果与非ARDS组比较,ARDS组血清eCIRP、suPAR水平升高(t/P=14.330/<0.001、10.632/<0.001);84例脓毒症致ARDS患者90 d死亡率为44.05%(37/84);死亡亚组患者血清eCIRP、suPAR、脓毒性休克比例、机械通气时间≥3 d比例、序贯器官衰竭评估(SOFA)评分、降钙素原、血乳酸均高于存活亚组(χ^(2)/t/P=13.805/<0.001、5.229/<0.001、10.932/0.001、4.334/0.037、4.850/<0.001、7.592/<0.001、5.926/<0.001);SOFA评分高、血乳酸高及血清eCIRP、suPAR高为脓毒症致ARDS患者死亡的独立危险因素[OR(95%CI)=1.523(1.123~2.067)、2.558(1.123~5.824)、1.094(1.017~1.178)、1.365(1.117~1.670)]。血清eCIRP、suPAR及二者联合预测脓毒症致ARDS患者死亡的AUC分别为0.787、0.779、0.871,二者联合的AUC大于血清eCIRP、suPAR水平的单独预测(Z/P=2.005/0.045、2.205/0.028)。结论血清eCIRP、suPAR水平升高与脓毒症致ARDS患者预后不良有关,且二者联合预测的价值较高。

球囊扩张联合导管接触溶栓治疗下肢深静脉血栓形成的效果

目的探讨球囊扩张联合导管接触溶栓(CDT)治疗下肢深静脉血栓形成(DVT)的效果。方法回顾性分析2017年11月至2023年12月于铜陵市人民医院血管外科诊断为DVT且接受CDT治疗的41例患者病历资料。根据术中是否采用球囊扩张分为观察组(球囊扩张联合CDT,20例)和对照组(单纯CDT,21例),比较2组患者的尿激酶用量、溶栓时间、住院时间、手术结束至复查纤维蛋白原达最低值所需时间、溶栓成功率、血栓清除时间、Villalta评分、纤维蛋白原变化量与静脉通畅率的相关性、消肿率。结果与对照组相比,观察组血栓清除时间更短[3(1,5)月比5(3,8)月,P<0.05]。在住院时间、尿激酶用量、溶栓时间上,观察组要明显少于对照组(P<0.05),手术结束至复查纤维蛋白原达最低值所需时间明显短于对照组[(15.45±8.14)h比(21.71±9.95)h,P<0.05]。观察组中,纤维蛋白原变化量与静脉通畅率存在线性相关关系。结论在DVT的治疗中,球囊扩张联合CDT较单纯CDT有更好的溶栓效果和更低的出血风险。

血清MIF、MCP-1、suPAR水平与脓毒症严重程度及合并ARDS风险的关系

目的探讨血清巨噬细胞迁移抑制因子(MIF)、单核细胞趋化蛋白-1(MCP-1)、可溶性尿激酶型纤溶酶原激活物受体(suPAR)水平与脓毒症严重程度及合并急性呼吸窘迫综合征(ARDS)风险的关系。方法回顾性分析2022年2月至2023年5月太原钢铁(集团)有限公司总医院收治的86例脓毒症患者的临床资料。依据病情程度不同将患者分为脓毒症组(n=20)、严重脓毒症组(n=48)和脓毒症休克组(n=18)。入院72 h内参考ARDS诊断标准将患者分为ARDS组(n=27)和非ARDS组(n=59)。检测并比较各组脓毒症患者血清MIF、MCP-1、suPAR水平。收集ARDS组与非ARDS组患者年龄、性别、体重指数、合并症、感染类型、既往史、心率、急性生理学和慢性健康状况评价Ⅱ(APACHEⅡ)、脓毒症相关性器官衰竭评价(SOFA)评分、白细胞计数、血乳酸、天冬氨酸转移酶(AST)、丙氨酸转移酶(ALT)、总胆固醇等指标。采用多因素Logistic回归分析对影响脓毒症患者并发ARDS的危险因素进行分析。通过受试者工作特征(ROC)曲线分析血清MIF、MCP-1、suPAR水平预测脓毒症患者并发ARDS的价值。结果脓毒症休克组患者血清MIF、MCP-1、suPAR水平分别为(94.02±10.13)、(506.55±45.15)、(13.89±3.95)ng/mL,均高于脓毒症组[(76.93±7.01)、(148.38±35.74)、(6.07±2.13)ng/mL]和严重脓毒症组[(85.46±8.74)、(327.08±40.62)、(8.42±1.07)ng/mL],而严重脓毒症组患者血清MIF、MCP-1、suPAR水平均高于脓毒症组,差异均有统计学意义(P<0.05)。ARDS组与非ARDS组患者的年龄、性别构成比、体重指数、合并症、感染类型、白细胞计数、心率、吸烟史、饮酒史、血乳酸、AST、ALT、总胆固醇比较,差异均无统计学意义(P>0.05);ARDS组患者APACHEⅡ评分、SOFA评分、有急腹症和胰腺炎占比及血清MIF、MCP-1、suPAR水平均高于非ARDS组,差异均有统计学意义(P<0.05)。经多因素Logistic回归分析结果显示,急腹症、胰腺炎、APACHEⅡ评分、SOFA评分、MIF、MCP-1、suPAR是影响脓毒症患者并发ARDS的独立危险因素(P<0.05)。经ROC曲线分析结果显示,血清MIF、MCP-1、suPAR水平均能预测脓毒症患者ARDS的发生,曲线下面积分别为0.904、0.910、0.917,预测价值较好(P<0.05)。结论血清MIF、MCP-1、suPAR水平与脓毒症患者病情程度、并发ARDS密切相关,且血清MIF、MCP-1、suPAR水平对ARDS的发生有较好的预测价值。

尿液足细胞生物标志物在诊断免疫球蛋白A肾病中的价值

目的筛选在免疫球蛋白A肾病(IgAN)的诊断中具有临床价值的尿液足细胞生物标志物,并分析其与临床病理特征的相关性。方法选取129例IgAN患者作为IgAN组,60例特发性膜性肾病(IMN)患者作为IMN组,63例健康志愿者作为健康组。检测并比较上述三组研究对象尿液中c‑Maf诱导蛋白(CMIP)、Ras同源基因家族成员A(RhoA)、丝切蛋白‑1(cofilin‑1)、可溶性尿激酶型纤溶酶原激活物受体(suPAR)、α‑klotho蛋白、肾病蛋白(nephrin)和足盂蛋白(PCX)的水平。应用受试者工作特征(ROC)曲线分析尿液足细胞生物标志物诊断IgAN的临床价值,应用Pearson或Spearman相关法分析尿液足细胞生物标志物与IgAN患者临床指标的相关性。结果IgAN与IMN组间、IgAN与健康组间的cofilin‑1和suPAR水平均存在差异(均P<0.05)。suPAR诊断IgAN的ROC曲线下面积为0.730,suPAR联合cofilin‑1诊断IgAN的ROC曲线下面积为0.772(均P<0.05)。相关性分析结果提示,suPAR与收缩压、24 h尿蛋白、总胆固醇、高密度脂蛋白、牛津病理评分E呈正相关,与白蛋白呈负相关;cofilin‑1与收缩压和舒张压均呈正相关,与估算肾小球滤过率呈负相关。结论IgAN患者的尿液足细胞生物标志物suPAR和cofilin‑1水平特异性升高,suPAR联合cofilin‑1在IgAN的无创诊断中有一定的价值。