Roles of tissue plasminogen activator and its inhibitor in proliferative diabetic retinopathy

AIMTo investigate the role of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) in proliferative diabetic retinopathy (PDR) and to discuss the correlations among t-PA, PAI and vascular endothelial growth factor (VEGF) expressions.

Comment on roles of tissue plasminogen activator and its inhibitor in proliferative diabetic retinopathy

Dear Sir,We congratulate Wu et al for their study entitled＂Roles of tissue plasminogen activator and its inhibitor in proliferative diabetic retinopathy＂.The authors investigated the effects of tissue plasminogen activator（t-PA）and plasminogen activator inhibitor（PAI）in the pathogenesis of proliferative diabetic retinopathy（PDR）.The authors reported that t-PA and PAI are involved in the pathogenesis of PDR.

tPA Involvement in Ovulation──Studies on Mechanism of Ovulation：Role of Tissue Type Plasminogen Activator

This review summarized our recent studies on involvement of tissue type plasminogen activator(tPA)and plasminogen activator inhibitor type 1(PAI-1) in process of ovulation.We have demonstrated that 1)hCG induces ovulation and coordinated tPA and PAI-1 gene expression in both rat and monkey ovaries;(2) GnRH and FSH are also capable of inducing ovulation by increasing ovarian tPA and PAI-1 gene expression in the same manner as hCG does;(3)Compounds which increase tPA production can induce oviation while compounds which decrease tPA and/or increase PAI-1 expression inhibit ovulation. Based on the data provided,a working model on the involvement of tPA in ovulation is presented.

Regulation of tissue-type plasminogen activator and plasminogen activator inhibitor type-1 in cultured rat Sertoli and Leydig cells

New data are provided to show that (i) rat Sertoli cells produce two types of plasminogen activators, tissue type (tPA) and urokinase type (uPA), and a plasminogen activator inhibitor type-1 (PAI-1); (ii) both tPA (but not uPA) and PAI-1 secretion in the culture are modified by FSH, forskolin, dbcAMP, GnRH, PMA and growth factors (EGF and FGF), but not by hCG and androstenedione (△4); (iii) in vitro secretion of tPA and PA-PAI-1 complexes of Sertoli cells are greatly enhanced by presence of Leydig cells which produce negligible tPA but measurable PAI-1 activity;(iv) combination culture of Sertoli and Leydig cells remarkably increases FSH-induced PAI-1 activity and decreases hCG- and forskolin-induced inhibitor activity as compared with that of two cell types cultured alone. These data suggest that rat Sertoli cells, similar to ovarian granulosa cells, are capable of secreting both tPA and uPA, as well as PAI-1. The interaction of Sertoli cells and Leydig cells is essential for the cells to response to hormone stimulation for tPA and PAI-1 secretion.

Identification and Possible Function of Tissue-type and Urokinase-type Plasminogen Activators and Plasminogen Activator Inhibitor in Corpus Luteum of Rhesus Monkey

Two types of plasminogen activators, tissue type (tPA) and urokinase type(uPA),and a plasminogen activator inhibitor (PAI-1) have been identified in ovariangranulosa cells (GC) of both rat and rhesus monkey. Interaction and coordinated expression of tPA and PAI-1 in the same tissue cells are closely related with certain reproductive processes such as ovulation, spermatogenesis and endometrium cycle. In our previous studies on gonadotropin-induced ovulation in rhesus monkeys,we

Effects of simvastatin on cigarette smoke extract induced tissue-type plasminogen activator and plasminogen activator inhibitor-1 expression in human umbilical vein endothelial cells

Background Cigarette smoking has an influence on both arterial-type and venous-type thrombosis. However, little is known about the direct effect of cigarette smoke extract （CSE） on fibrinolytic activity of human umbilical vein endothelial cells （HUVECs）. Most recently, simvastatin has been marked in its effect on endothelial cells protection and anticoagulation. In this study, the effect of CSE on the expression of tissue-type plasminogen activator （t-PA） and plasminogen activator inhibitor-l（PAl-1） in HUVECs was addressed. The role of simvastatin in CSE-induced fibrinolytic activity changes was investigated as well. Methods The fourth to fifth generation of HUVECs were incubated respectively with 0, 5%, 10% and 20% CSE for 6 hours or exposed to 5% CSE for 0, 4, 6, 8, 12, 24 hours to determine the expression changes of t-PA and PAl-1 protein. Meanwhile, cells were also accordingly exposed either to 5% CSE alone or simvastatin pre-treated and 5% CSE for 24 hours to assess the role of simvastatin in CSE-induced t-PA and PAl-1 protein and mRNA expression in HUVECs. RT-PCR and ELISA techniques were used for detecting the t-PA or PAl-1 mRNA and protein. Results After 6-hour exposure to CSE, the expression levels of t-PA protein in 10% and 20% CSE-treated groups reduced significantly （（0.0365±0.0083） ng/ml, （0.0255±0.0087） ng/ml） when compared with that of control group （（0.0660±0.0120） ng/ml） （P 〈0.05）. In contrast, the levels of PAl-1 protein in 5%, 10% and 20% CSE-treated groups increased remarkably （（13.3225±0.5680） ng/ml, （14.2675±1.5380） ng/ml, （14.4292±1.6230） ng/ml） when compared with that of control group （（8.5193_±0.7537）ng/ml） （P〈0.05）. After stimulation with 5% CSE for 0, 4, 6, 8, 12, 24 hours, the levels of PAl-1 protein increased over time and reached the peak at 24 hours （（14.6400±1.0651） ng/ml）, which was significantly higher than that of control group （（12.0656±0.6148） ng/ml） （P 〈0.05）. Additionally, CSE could up-regulate PAl-1 expression at both the mRNA and the protein levels. The levels of PAl-1 mRNA and protein increased significantly in 5% CSE-treated group （（8.8030±0.4745） ng/ml, （1.8155±0.0412） ng/ml） compared with those of control groups （（5.0588±0.2315） ng/ml, （1.3030±0.0647） ng/ml） （P 〈0.01）, and decreased after 2-hour simvastatin pre-treatment （（5.4875±0.3166） ng/ml, （1.3975-±0.0297） ng/ml） （P 〈0.01）. No significant difference was found at the levels of t-PA protein and mRNA （P 〉0.05）. Conclusions CSE inhibits the fibrinolytic activity of HUVECs in vitro. Simvastatin plays a protective role in CSE-induced fibrinolytic malfunction.

Identification of secretion sites of tissue plasminogen activator and plasminogen activator inhibitor type-1 in basal plates of human and rhesus monkey placentae

INCREASING evidence has demonstrated that the locally controlled proteolytic activity generatedby coordinated expression of tPA and PAI-1 in different tissues may play an important role inmany reproductive events. These are largely related to fibrinolytic activity. They include folli-cle rupture, luteolysis, spermatogenesis and trophoblast implantation. Parturition, whichis a complex process, may also be associated with tissue destruction. Detachment of placentaldecidua and partial breakdown of fetal membranes are possible examples. It has been

Role of Connective Tissue Growth Factor in Extracellular Matrix Degradation in Renal Tubular Epithelial Cells

In order to investigate the effects of connective tissue growth factor （CTGF） antisense oligodeoxynucleotide （ODN） on plasminogen activator inhibitor-1 （PAI-1） expression in renal tubular cells induced by transforming growth factor β1 （TGF-β1） and to explore the role of CTGF in the degradation of renal extracellular matrix （ECM）, a human proximal tubular epithelial cell line （HKC） was cultured in vitro. Cationic lipid-mediated CTGF antisense ODN was transfected into HKC. After HKC were stimulated with TGF-β1 （5 μg/L）, the mRNA level of PAI-1 was detected by RT-PCR. Intracellular PAI-1 protein synthesis was assessed by flow cytometry. The secreted PAI-1 in the media was determined by Western blot. The results showed that TGF-β1 could induce tubular CTGF and PAI-1 mRNA expression. The PAI-1 mRNA expression induced by TGF-β1 was significantly inhibited by CTGF antisense ODN. CTGF antisense ODN also inhibited intracellular PAI-1 protein synthesis and lowered the levels of PAI-1 protein secreted into the media. It was concluded that CTGF might play a crucial role in the degradation of excessive ECM during tubulointerstitial fibrosis, and blocking the biological effect of CTGF may he a novel way in preventing renal fibrosis.

Expression of Connective Tissue Growth Factor in Renal Tubulointerstitial Fibrosis in Rats and Its Pathogenic Role

Summary： In order to explore the role of connective tissue growth factor （CTGF） in the pathogenesis of renal tubulointerstitial fibrosis, 48 Wistar rats were randomly divided into sham-operated and unilateral ureteral obstruction （UUO） group. On the postoperative day 1, 3, 7 and 14, the rats were killed and the kidneys were removed. The renal tubulointerstitial injury index was evaluated according to the MASSON staining. The mRNA levels of CTGF, transforming growth factor β1 （TGF-β1）. collagen [ （col I ）, and plasminogen activator inhibitor-1 （PAI 1） were detected using rexerse transcriptional-polymerase chain reaction （RT PCR）. Immunohistochemistry was performed to evaluale the protein expression of the above factors, and the relations among them were analyzed. Quantitative expression of CTGF protein in the kidneys was also assessed using Western blot. The results showed that TGF-β1 mRNA level was increased at first day after UUO, followed by a marked elevation of CTGF mRNA level, which began to increase 3 days after UUO （P〈0.01）. With the progression of the disease, the mRNA expression of CTGF, col I and PAI-1 was increased progressively. Immunohistochemistry revealed that the CTGF protein expression was significantly increased in fibrotic areas and tubular epithelial cells 3 days after UUO. On the post-UUO day 7, the protein level of CTGF was positively related to the renal tubulointerstitial injury index （r =0.62, P〈0.01）, the expression of TGF-β1 （r=0.85, P〈0.01）, colI （r=0.78, P〈0.01）, and PAI-1（r=0.76, P〈0.01）. Upon Western blot analysis, CTGF protein expression began to increase 3 days after UUO, and appeared progressively throughout the time course （P〈0.01, as compared with sham-operated group）. It is concluded that CTGF can be induced by TGF-β and mediate various profibrotic actions of this cytokine, such as increasing extracellular matrix （ECM） synthesis and decreasing ECM degradation. The increased expression of CTGF may play a crucial role in the development and progression of tubulointerstitial fibrosis.

Evaluate the Expression of uPA,PAI-1 in Human Gastric Cancer and its Correlation with the Angiogenesis by the Application of Tissue Microarray

OBJECTIVE To investigate the expression of urokinase-type plasminogen （uPA）, its inhibitor-1 （PAI-1） mRNA and its protein in human gastric cancer and to find out the relationship among the tumor differentiation, angiogenesis, and other clinical pathologic factors. METHODS In situ hybridization （ISH） was used to get the uPA, PAI-lmRNA in 110 cases with human gastric cancer in 2-tissue microarray （TMA）. Immunohistochemical staining （S-P method） for uPA, PAI-1 protein and CD34 were performed in the 110 cases in 2 TMA. RESULTS The expression of the uPA, PAI-lmRNA and their protein happened in the cytoplasm of gastric cancer cells were induced by the poor differentiation of the GC, and the expression of uPA had an increasing trend while the expression of the PAI-1 had a decreasing trend. The microvessel density （MVD） had a positive correlation with the clinical stages and the significant relationship with the lymph node metastasis （P 〈 0.05）. The MVD in uPA positive group was significantly higher than those in uPA negative group （P 〈 0.05）. The expression of PAI-1 has no correlation neither with the clinical stages nor the lymph node metastasis. CONCLUSION The uPA play an important role in invasion and metastasis of GC through promoting angiogenesis. Interdicting the secretion and function of the uPA may allow the target therapy against the tumor invasion. As a new high-throughput technology, the tissue microarray is a valuable way to be used in clinical treatment.

新凝血标志物在新生儿弥漫性血管内凝血诊断及预后评估中的价值

目的探讨新凝血标志物血栓调节蛋白(TM)、凝血酶-抗凝血酶复合物(TAT)、纤溶酶-α2抗纤溶酶复合物(PIC)和组织型纤溶酶原激活剂-纤溶酶原激活剂抑制剂-1复合物(t-PAIC)在新生儿弥漫性血管内凝血(DIC)诊断及预后评估中的价值。方法纳入87例DIC患儿(观察组),根据其出院时的转归情况分为存活组(66例)和死亡组(21例),另外以同期出生的50例健康新生儿作为对照组。收集新生儿的临床资料,采用Logistic回归分析新生儿发生DIC的危险因素。分析不同组别TM、TAT、PIC和t-PAIC水平差异。采用受试者工作特征(ROC)曲线分析TM、TAT、PIC和t-PAIC在新生儿DIC诊断和预后评估中的价值。结果观察组低Apgar评分、出生窒息、IVH、脓毒症和PIH的发生率高于对照组(P<0.05)。多因素Logistic回归分析显示,低Apgar评分、出生窒息、脓毒症和PIH是新生儿发生DIC的独立危险因素。观察组TM、TAT、PIC和t-PAIC水平均高于对照组(P<0.05)。ROC曲线显示,TM、TAT、PIC和t-PAIC联合诊断新生儿DIC的价值优于单独诊断。死亡组TM、TAT水平高于存活组(P<0.05),2组PIC、t-PAIC差异无统计学意义;多因素Logistic回归分析显示,TAT水平升高是影响新生儿DIC预后的独立危险因素。ROC曲线显示,当TAT为21.72μg/L时,其预测新生儿DIC预后的曲线下面积为0.772(95%CI:0.666~0.878),敏感度和特异度分别为76.2%和71.2%。结论TM、TAT、PIC和t-PAIC联合应用对新生儿DIC诊断和预后评估具有重要的临床价值。

TAT、TM、PIC、t-PAIC与重型血液毒毒蛇咬伤中毒患者DIC的相关性及预测价值

目的评估凝血酶抗凝酶复合物(TAT)、血栓调节蛋白(TM)、纤溶酶-抗纤溶酶复合物(PIC)和组织型纤溶酶原激活抑制复合物(t-PAIC)与重型血液毒毒蛇咬伤中毒后弥散性血管内凝血(DIC)的临床相关性及预测价值。方法连续纳入2019年4月至2023年4月收治的重型血液毒毒蛇咬伤中毒患者作为研究对象,共132例。依据住院期间是否出现DIC分为观察组(发生DIC,n=37)及对照组(未发生DIC,n=95)。检测2组血浆TAT、TM、PIC、t-PAIC浓度。应用二元、无分类协变量的非条件Logistic回归分析TAT、TM、PIC、t-PAIC浓度与重型血液毒毒蛇咬伤中毒后DIC的临床相关性,建立受试者工作特征(ROC)曲线分析TAT、TM、PIC、t-PAIC对重型血液毒毒蛇咬伤中毒后DIC的预测能力。结果观察组TAT、TM、PIC、t-PAIC显著高于对照组(P<0.05)。二元、无分类协变量的非条件Logistic回归分析显示,TAT[OR=1.517(95%CI:1.155,1.879)]、TM[OR=1.647(95%CI:1.108,2.186)]、PIC[OR=3.989(95%CI:2.986,4.992)]、t-PAIC[OR=1.111(95%CI:0.854,1.368)]是重型血液毒毒蛇咬伤中毒患者发生DIC的危险因素(P<0.05)。ROC曲线分析显示,TAT、TM、PIC、t-PAIC是预测重型血液毒毒蛇咬伤中毒患者DIC的有效指标(P<0.05),其曲线下面积(AUC)分别为0.865(95%CI:0.790,0.939)、0.771(95%CI:0.673,0.870)、0.847(95%CI:0.804,0.889)、0.680(95%CI:0.573,0.787),联合预测效能更优异(P<0.001),AUC为0.904(95%CI:0.875,0.933)。结论TAT、TM、PIC和t-PAIC检测对判断重型血液毒毒蛇咬伤中毒患者是否发生DIC有重要参考价值,可以较好地评估患者凝血功能状态,4个指标联合预测DIC的效能更优。

透析液中结缔组织生长因子、纤溶酶水平与腹膜透析患者腹膜溶质转运速率的关系

目的 探讨透析液中结缔组织生长因子(CTGF)、纤溶酶原激活物抑制剂-1(PAI-1)水平与腹膜透析(PD患者腹膜溶质转运速率(PSTR)的关系。方法 选取2020年1月至2022年12月江苏省连云港市第二人民医院收治的152例PD患者,根据标准腹膜平衡试验分为快速转运组和非快速转运组。采用酶联免疫吸附试验检测透析液中CTGF、PAI-1水平。采用多因素logistic回归分析PD患者PSTR快速转运的影响因素,采用受试者操作特征曲线分析透析液中CTGF、PAI-1水平对PD患者PSTR快速转运的评估价值。结果 152例PD患者PSTR快速转运发生率为57.24%(87/152)。快速转运组透析液中CTGF、PAI-1水平高于非快速转运组(P<0.05)。快速转运组透析龄、夜间超滤量高于非快速转运组,白蛋白水平低于非快速转运组(P<0.05)。透析龄延长(OR=1.051,95%CI:1.023~1.081)和CTGF(OR=1.298,95%CI:1.165~1.446)、PAI-1(OR=1.408,95%CI:1.205~1.646)升高为PD患者PSTR快速转运的独立危险因素(P<0.05)。透析液中CTGF联合PAI-1预测PD患者PSTR快速转运的曲线下面积大于二者单独预测(P<0.05)。结论 透析液中CTGF、PAI-1水平升高与PD患者PSTR快速转运独立相关,二者联合对PD患者PSTR快速转运评估价值较高,可能成为PD患者PSTR快速转运的辅助评估指标。

t-PAIC、TM和血栓弹力图在溃疡性结肠炎患者活动度评估中的应用

目的探讨组织纤溶酶原激活物-抑制剂复合物(t-PAIC)、血栓调节蛋白(TM)在溃疡性结肠炎(UC)患者中的水平,以及t-PAIC、TM和血栓弹力图(TEG)评估UC患者活动度的价值。方法选取2021年2月至2023年3月在新乡市第二人民医院住院治疗的82例UC患者为试验组,按照1∶1的比例同时选取同期在新乡市第二人民医院体检的82例健康体检者作为对照组。比较试验组及对照组纤维蛋白(原)降解产物(FDP)、D-二聚体(D-D)、t-PAIC、TM水平及TEG各指标[凝血反应时间(R)、血块动力时间(K)、凝固角(Angle角)、纤维蛋白溶解率(LY30)及最大振幅(MA)]差异。根据改良Mayo评分系统对UC患者进行分组并比较不同病情各组之间FDP、D-D、t-PAIC、TM水平及TEG各指标差异。采用多因素Logistic回归分析t-PAIC、TM和TEG各指标对UC患者疾病活动指数评分的影响;采用受试者工作特征(ROC)曲线分析各指标对UC患者活动度的评估价值。结果与对照组相比,试验组血清FDP、D-D、t-PAIC、TM水平明显升高(P<0.05)。TEG检测结果显示试验组R、K明显低于对照组,Angle角、LY30及MA明显高于对照组,差异均有统计学意义(P<0.05)。根据改良Mayo评分将82例UC患者分为缓解期组8例,轻度活动组26例,中度活动组29例及重度活动组19例。UC不同病情各组间FDP、D-D、t-PAIC、TM水平及R、K、Angle角、LY30、MA比较,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,t-PAIC、TM、LY30是UC患者疾病活动度的影响因素(OR=1.719、1.531、2.067,均P<0.05)。以Mayo评分<6分的UC患者为对照,绘制ROC曲线,结果显示t-PAIC、TM、LY30鉴别诊断UC患者活动度的曲线下面积(AUC)分别为0.784(95%CI:0.684~0.883)、0.738(95%CI:0.629~0.847)、0.826(95%CI:0.737~0.916)。结论t-PAIC、TM及LY30是UC患者疾病活动度的影响因素,检测t-PAIC、TM及LY30可以有效评估UC患者的活动度。

腹腔镜子宫肌瘤切除术全麻复合硬膜外麻醉效果及对预后影响

目的:探究腹腔镜子宫肌瘤切除术全麻复合硬膜外麻醉对患者纤溶功能指标纤溶酶原激活物抑制剂-1(PAI-1)、组织型纤溶酶原激活剂(t-PA)、D-二聚体(D-D)及预后的影响.方法:随机选取本院2018年3月-2023年3月收治拟行腹腔镜手术的的子宫肌瘤患者96例,分为联合组和单纯组各48例,分别采用全麻复合硬膜外麻醉或静吸复合全麻干预;对比两组麻醉效果,干预前后纤溶功能、血流动力学、性激素及不良反应和预后指标.结果:麻醉后联合组PAI-1(26.52±3.54μg/L)、t-PA(15.67±2.89μg/L)、D-D(155.62±21.47μg/L)水平均低于单纯组(41.32±4.82μg/L、22.39±3.16μg/L、189.41±22.59μg/L),心率、平均动脉压水平低于单纯组,麻醉效果优于单纯组,卵泡刺激素、黄体生成激素水平低于单纯组,雌二醇水平高于单纯组,不良反应发生率(10.4%)低于单纯组(29.2%),月经转归率(95.8%)高于单纯组(81.3%),复发率(4.2%)低于单纯组(16.7%)(均P<0.05).结论:腹腔镜子宫肌瘤切除术中使用全麻复合硬膜外麻醉可改善患者纤溶功能、血流动力学和性激素指标,麻醉效果更优,不良反应降低且预后较好.

脓毒症合并心肌损伤患者血清t-PAI-C、HBP、HMGB1水平与预后的关系研究

目的 探究脓毒症合并心肌损伤患者血清组织纤溶酶原激活物-纤溶酶原激活物抑剂-1复合物(t-PAI-C)、肝素结合蛋白(HBP)、外周血高迁移率组蛋白B1(HMGB1)水平与其预后的关系。方法 回顾性分析2020年3月至2023年3月蚌埠医学院第一附属医院收治的105例脓毒症合并心肌损伤患者的临床资料,依据患者治疗后28 d存活情况将其分为存活组与死亡组。比较两组临床资料(性别、年龄、体重指数、感染部位、平均动脉压、射血分数)、血清心肌肌钙蛋白I(cTnI)、t-PAI-C、HBP、HMGB1水平以及急性生理学和慢性健康状况评价Ⅱ(APACHEⅡ)评分,分析影响脓毒症合并心肌损伤患者预后的影响因素;探究t-PAI-C、HBP、HMGB1水平与cTnI、APACHEⅡ评分的相关性;绘制受试者工作特征(ROC)曲线分析t-PAI-C、HBP、HMGB1诊断脓毒症合并心肌损伤患者预后的价值。结果 脓毒症合并心肌损伤患者随访期间出现死亡30例(28.57%),存活75例(71.43%)。死亡组患者的cTnI、t-PAI-C、HBP、HMGB1水平以及APACHEⅡ评分分别为(1.58±0.43)μg/L、(16.75±4.00)ng/mL、(45.68±9.25)ng/mL、(125.00±20.18)μg/L、(17.63±2.66)分,均高于存活组[(0.65±0.11)μg/L、(13.20±2.68)ng/mL、(38.00±8.63)ng/mL、(96.69±11.25)μg/L、(11.50±1.68)分],差异均有统计学意义(P<0.05)。cTnI、t-PAI-C、HBP、HMGB1以及APACHEⅡ评分均为影响脓毒症合并心肌损伤患者预后的独立危险因素(P<0.05)。t-PAI-C、HBP、HMGB1与cTnI、APACHEⅡ评分之间均呈正相关(P<0.05)。t-PAI-C、HBP、HMGB1三者联合诊断脓毒症合并心肌损伤患者预后的曲线下面积(AUC)为0.950(0.889~0.983),敏感度与特异度分别为83.33%和93.33%,诊断效能均优于单一的t-PAI-C、HBP、HMGB1指标(P<0.05)。结论 t-PAI-C、HBP、HMGB1水平与cTnI、APACHEⅡ评分相关性较好,可作为临床诊断脓毒症合并心肌损伤的潜在生物学标记物,三者联合预测脓毒症合并心肌损伤患者预后效能较好。

血清TAT、t-PAIC、TM水平与颅内动脉粥样硬化性狭窄程度的相关性分析

[目的]探讨凝血酶-抗凝血酶复合物(TAT)、组织型纤溶酶原激活物-抑制剂复合物(t-PAIC)、血栓调节蛋白(TM)在颅内动脉粥样硬化性狭窄(ICAS)患者血清中的水平,以及它们与狭窄程度的相关性。[方法]收集沧州市人民医院2021年1月—2023年2月期间进行治疗的196例ICAS患者(ICAS组)作为研究对象,根据血管的狭窄程度,将其分为轻度组(n=78)、中度组(n=64)和重度组(n=54);另选取196例与ICAS患者临床基本资料一致的同期门诊健康体检者作为对照组。比较各组血清TAT、t-PAIC、TM水平;Spearman法分析ICAS患者血清TAT、t-PAIC、TM水平与狭窄程度的相关性;多因素Logistic回归分析ICAS患者重度狭窄的影响因素;ROC曲线分析血清TAT、t-PAIC、TM、总胆固醇(TC)水平对ICAS患者发生重度狭窄的预测价值。[结果]与对照组相比,ICAS组血清TAT、t-PAIC、TM水平显著升高(P<0.05);ICAS轻度组、中度组、重度组血清TAT、t-PAIC、TM、TC水平依次升高,差异有统计学意义(P<0.05)。Spearman分析显示,ICAS患者血清TAT、t-PAIC、TM水平分别与狭窄程度呈正相关(r=0.574,0.695,0.628;均P<0.05)。多因素Logistic回归分析结果显示,TAT、t-PAIC、TM、TC是ICAS患者发生重度狭窄的独立危险因素(P<0.05)。ROC曲线显示,TAT、t-PAIC、TM、TC联合检测预测ICAS患者发生重度狭窄的AUC为0.927,灵敏度为83.33%,特异度为86.62%,优于各自单独预测(Z_(联合检测-TAT)=4.617、Z_(联合检测-t-PAIC)=4.024、Z_(联合检测-TM)=4.004、Z_(联合检测-TC)=7.078,均P=0.000)。[结论]ICAS患者血清TAT、t-PAIC、TM水平显著升高,且与狭窄严重程度呈正相关,这三者和TC联合检测对ICAS患者发生重度狭窄具有较高的预测价值。

血栓标志物联合炎症指标评估肿瘤并发脓毒性休克的效能

目的探讨血栓标志物[包括凝血酶-抗凝血酶复合物(TAT)、纤溶酶-α2纤溶酶抑制剂复合物(PIC)、血栓调节蛋白(TM)与组织型纤溶酶原激活剂-抑制物复合物(t-PAI.C)]及相关炎症指标[包括白细胞介素-6(IL-6)、降钙素原(PCT)与白细胞计数(WBC)]诊断肿瘤并发脓毒性休克的价值。方法选取2022年1月至2023年6月在国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院深圳医院就诊的74例肿瘤并发脓毒症患者为研究对象,按照脓毒症3.0诊断标准将74例患者分为脓毒症组54例和脓毒性休克组20例。比较两组血栓标志物及炎症指标水平。采用多因素Logistic回归分析肿瘤并发脓毒性休克的危险因素;采用受试者工作特征(ROC)曲线分析各项指标对肿瘤并发脓毒性休克的诊断价值。结果脓毒症组TM、t-PAI.C、PCT水平明显低于脓毒性休克组,差异有统计学意义(P<0.05)。将TM、t-PAI.C与PCT纳入多因素Logistic回归分析,结果显示,仅t-PAIC水平升高为肿瘤并发脓毒性休克的独立危险因素(OR=1.19,95%CI 1.08~1.30,P<0.05),患者t-PAIC水平每增加1 ng/mL,肿瘤并发脓毒性休克的风险增加至1.19倍。TM、t-PAI.C、PCT及3项指标联合检测诊断肿瘤并发脓毒性休克的曲线下面积分别为0.64、0.88、0.77与0.90,其诊断肿瘤并发脓毒性休克的灵敏度分别为70.0%、85.2%、86.6%与88.9%,特异度分别为60.0%、84.0%、56.0%与84.0%。结论TM、t-PAI.C、PCT联合检测诊断脓毒性休克的效能优于单一指标,能更准确地诊断肿瘤患者发生脓毒性休克,从而协助临床进行干预治疗。

凝血相关指标在评估危重症患者静脉血栓栓塞风险中的应用

目的探讨血栓调节素(TM)、凝血酶-抗凝血酶复合物(TAT)、α2-纤溶酶抑制剂-纤溶酶复合物(PIC)和组织纤溶酶原激活物-抑制剂复合物(t-PAIC)在评估危重症患者静脉血栓栓塞(VTE)风险和预后中的价值。方法纳入2020年10月—2022年11月本院ICU收治的254例危重症患者资料行回顾性分析。根据有无VTE分为VTE组(106例)和无VTE组(148)。使用高灵敏度化学发光酶免疫测定法测量患者空腹静脉血中TAT、PIC、TM和t-PAIC水平。使用二元逻辑回归分析TAT、PIC、TM、t-PAIC和VTE之间的关系。采用受试者工作特征(ROC)曲线评价它们在区分VTE中的诊断效率。使用Kaplan-Meier方法估计患者的28 d存活率。结果在纳入患者中,VTE发生率41.7%,包括16.5%肺血栓栓塞(PE),20.5%深静脉血栓(DVT)和4.7%其他(静脉导管或浅静脉)血栓形成。与无VTE组相比,VTE组入院时血管加压药使用比例、机械通气比例、CRP水平、TAT、PIC、TM、t-PAIC、D-二聚体、纤维蛋白降解产物水平显著升高(均P<0.05)。多变量分析显示TAT、PIC、TM、t-PAIC与危重症患者VTE密切相关(P<0.05)。在4个凝血标志物中,tPAIC的最低曲线下面积(AUC)为0.615,TAT的最高AUC为0.711。当应用TAT、PIC、TM、t-PAIC的组合时,AUC增加到0.814,敏感性增加到74.1%。在4种凝血标志物中,TAT、PIC和TM高水平患者的28 d存活率显著低于低水平患者(P<0.05)。结论TAT、PIC、TM、t-PAIC联合在评估危重症患者VTE中表现出良好的诊断性能,并优于单一标志物。

脓毒症性肝损伤的临床特征及危险因素分析

目的探讨脓毒症性肝损伤患者的临床特征并分析相关危险因素。方法回顾性分析联勤保障部队第九〇八医院重症医学科2018年5月至2022年12月收治的678例脓毒症患者的临床资料。根据入科2 h内是否存在急性肝损伤将患者分为普通脓毒症组(n=563例)和脓毒症性肝损伤组(n=115例),运用Logistic回归分析脓毒症性肝损伤的危险因素,并绘制ROC曲线评估其对预测脓毒症性肝损伤的价值。结果与普通脓毒症组相比,脓毒症性肝损伤组患者的血小板计数(PLT)和白蛋白水平明显下降,而血浆丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素、血肌酐、C⁃反应蛋白(CRP)、乳酸、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白降解产物(FDP)、D⁃二聚体、凝血酶调节蛋白(TM)、凝血酶⁃抗凝血酶复合物(TAT)、组织型纤溶酶原激活物⁃抑制剂复合物(t⁃PAIC)浓度均显著升高,差异有统计学意义(P<0.05)。多因素Logistic回归分析显示,t⁃PAIC、PLT、CRP是脓毒症性肝损伤的独立危险因素(P<0.05)。ROC曲线分析结果显示,t⁃PAIC、PLT、CRP及三者联合对脓毒症性肝损伤的预测价值的曲线下面积(AUC)分别为0.699(95%CI:0.645~0.754,P<0.001)、0.665(95%CI:0.610~0.720,P<0.001)、0.640(95%CI:0.584~0.697,P<0.001)和0.797(95%CI:0.752~0.841,P<0.001)。结论PLT减少、血浆t⁃PAIC和CRP水平升高是脓毒症性肝损伤的独立危险因素,三者联合对脓毒症性肝损伤具有较好的诊断价值。