Soluble ST2:A Novel Biomarker for Diagnosis and Prognosis of Cardiovascular Disease

The increasing incidence of cardiovascular disease(CVD)is a significant global health concern,affecting millions of individuals each year.Accurate diagnosis of acute CVD poses a formidable challenge,as misdiagnosis can significantly decrease patient survival rates.Traditional biomarkers have played a vital role in the diagnosis and prognosis of CVDs,but they can be influenced by various factors,such as age,sex,and renal function.Soluble ST2(sST2)is a novel biomarker that is closely associated with different CVDs.Its low reference change value makes it suitable for continuous measurement,unaffected by age,kidney function,and other confounding factors,facilitating risk stratification of CVDs.Furthermore,the combination of sST2 with other biomarkers can enhance diagnostic accuracy and prognostic value.This review aims to provide a comprehensive overview of sST2,focusing on its diagnostic and prognostic value as a myocardial marker for different types of CVDs and discussing the current limitations of sST2.

急性冠脉综合征患者血清sST2及NLRP3水平与介入术后无复流-慢血流的相关性分析

目的探讨急性冠脉综合征(acute coronary syndrome,Acs)患者血清可溶性生长刺激表达基因蛋白2(soluble growth stimulation expression gene 2 protein,sST2),核苷酸寡聚化结构域样受体热蛋白结构域相关蛋白3(nucleotide oligomerization domain like receptor heat protein domain associated protein 3,NLRP3)水平与经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)术后无复流-慢血流的关系。方法选择2020年1月~2022年12月佳木斯市中心医院收治的97例急性冠脉综合征患者,所有患者均接受PCI治疗,根据术后无复流-慢血流发生情况分为无复流-慢血流组(n=20)和对照组(n=77)。术前检测血清sST2及NLRP3水平,分析影响急性冠脉综合征患者PCI术后无复流-慢血流的因素以及sST2,NLRP3预测急性冠脉综合征患者PCI术后无复流-慢血流的价值。结果无复流-慢血流组血清sST2(14.32±2.65 ng/ml vs 11.02±2.13 ng/ml),NLRP3(68.23±10.17 pg/ml vs 42.05±8.23 pg/ml)水平高于对照组,差异具有统计学意义(t=5.860,12.055,均P<0.05)。多因素Logistic回归分析显示高血栓负荷(OR:7.791,95%CI:2.834~21.421)、高水平sST2(OR=2.071,95%CI:1.146~3.743)、高水平NLRP3(OR=2.008,95%CI:1.228~3.284)是急性冠脉综合征患者PCI术后无复流-慢血流的危险因素(均P<0.05)。sST2,NLRP3诊断急性冠脉综合征患者PCI术后无复流-慢血流的临界值分别为12.91ng/ml,55.39 pg/ml,曲线下面积分别为0.737,0.686,联合sST2,NLRP3诊断急性冠脉综合征患者PCI术后无复流-慢血流的曲线下面积为0.907,高于单独诊断(Z=2.662,2.856,均P<0.05)。结论急性冠脉综合征患者血清sST2,NLRP3水平增高与PCI术后无复流-慢血流的发生有关,联合检测sST2和NLRP3可提高对术后无复流-慢血流的诊断效能。

Changes in soluble interleukin-2 receptor level in serum and Na^+ -K^+ -exchanging ATPase activity in semen of infertile men caused by antisperm antibody

Aim: To explore the possible mechanisms of male infertility caused by antisperm antibody (AsAb). Methods: Thesoluble interleukin-2 receptor (sIL-2R) level in serum was analyzed by ELISA and Na^+ -K^+ -exchanging ATPase activi-ty in semen by phosphorus (Pi) assay. Results: The slL-2R level in serum was significantly higher and the Na^+ -K^+ -exchanging ATPase activity in semen significantly lower in AsAb positive infertile men when compared with thecontrols. Conclusion: The AsAb titer varies with the slL-2R level in serum. A decrease in Na^+ -K^+ -exchangingATPase activity in semen may play a role in male infertility caused by AsAb.

Increased serum levels of soluble CD146 and vascular endothelial growth factor receptor 2 in patients with exudative age-related macular degeneration

AIM: To investigate serum levels of soluble CD146(s CD146) and vascular endothelial growth factor receptor 2(VEGFR2) in patients with age-related macular degeneration(AMD). METHODS: Eighty-eight patients with exudative AMD and 45 sex-and age-matched healthy controls were enrolled in this study conducted in China. Serum samples was obtained from the patients with exudative AMD and from the controls. Serum sCD146 and VEGFR2 protein levels were measured using an enzyme-linked immunosorbent assay.RESULTS: We found that serum sCD146 and VEGFR2 protein levels were significantly higher in the patients with exudative AMD group than in the controls(t=3.859, P<0.001 and t=3.829, P<0.001, respectively). Serum sCD146 levels were significantly higher in patients with classic choroidal neovascularization(CNV) than in those with occult CNV(t=9.899, P<0.001). There was a significant difference in the trend for exudative AMD in the highest versus lowest quartile of circulating sCD146 levels(χ2=10.29, P=0.001). The receiver operating characteristic curve analysis showed that the area under the curve was 0.696 for s CD146(95%CI: 0.601-0.791) with an optimum diagnostic cut-off value of 157.16 ng/mL, a sensitivity of 55.7%, and a specificity of 82.2%.CONCLUSION: The serum sCD146 level increases and may be a biomarker for exudative AMD.

Serum soluble ST2 is a promising prognostic biomarker in HBV-related acute-on-chronic liver failure

BACKGROUND： The IL-33/ST2 axis is involved in the pathogenesis of many diseases such as autoimmune diseases, cancer,and heart failure. However, studies of the IL-33/ST2 pathway in HBV-related acute-on-chronic liver failure（HBV-ACLF） are lacking. The present study aimed to determine the prognostic role of serum IL-33/soluble ST2（s ST2） in HBV-ACLF.METHODS： Serum levels of IL-33 and sS T2 in healthy controls（HC, n=18）, chronic hepatitis B（CHB, n=27） and HBV-ACLF（n=51） patients at the 1st and 4th week after enrollment were detected using ELISA, and clinical data were collected. The follow-up of HBV-ACLF patients lasted for 6 months at least.RESULTS： There was no significant difference of serum IL-33 level among HC, CHB and HBV-ACLF patients at week 1.However, serum s ST2 level differed significantly among the three groups： highest in the HBV-ACLF group, moderate in the CHB group and lowest in the HC group. There was a reverse correlation between serum s ST2 level and the survival of HBV-ACLF patients. The level of serum s ST2 in HBV-ACLF survivors was significantly declined from week 1 to week 4 following the treatment, whereas that in HBV-ACLF nonsurvivors remained at a high level during the same period. Furthermore, serum sS T2 level was significantly correlated with laboratory parameters and the most updated prognostic scores（CLIF-C OF score, CLIF-C ACLF score and ACLF grades）. Thereceiver operating characteristics curves demonstrated that serum sS T2 level was a good diagnostic marker for predicting the 6-month mortality in HBV-ACLF patients, comparable to the most updated prognostic scores. Serum sS T2 cut-off points for predicting prognosis in HBV-ACLF patients were 76 ng/mL at week 1 or 53 ng/mL at week 4, respectively. HBV-ACLF patients with serum sS T2 level above the cut-off point often had a worse prognosis than those below the cut-off point.CONCLUSION： Serum s ST2 may act as a promising biomarker to assess severity and predict prognosis of patients with HBV-ACLF and help for the early identification and optimal treatment of HBV-ACLF patients at high risk of mortality.

Serum soluble interleukin-2 receptor levels in patients with chronic hepatitis B virus infection and its relation with antiHBc

AIM： To investigate the relationship between serum soluble interleukin-2 receptor （sIL-2R） level and anti-HBc in patients with chronic hepatitis B virus （HBV） infection. METHODS： Sera from 100 patients with chronic HBV infection and 30 healthy controls were included in this study. The patients were divided into group A [HBsAg （＋）, HBeAg （＋） and anti-HBc （＋）, n = 50] and group B [HBsAg （＋）, HBeAg （＋） and anti-HBc （-）, n = 50]. sIL-2R levels were determined using ELISA. HBV DNA and alanine aminotransferase （ALT） were also detected. RESULTS： Serum sIL-2R levels were significantly higher in patients with chronic HBV infection than in healthy controls. Moreover, serum sIL-2R levels were significantly higher in patients with HBsAg （＋）, HBeAg （＋） and antiHBc （＋） （976.56±213.51×10^3 U/L） than in patients with HBsAg （＋）, HBeAg （＋） and anti-HBc （-） （393.41±189.54 ×10^3 U/L, P〈 0.01）. A significant relationship was found between serum sIL-2R and ALT levels （P〈 0.01） in patients with chronic HBV infection, but there was no correlation between sIL-2R and HBV DNA levels. The anti-HBc status was significantly related to the age of patients （P〈 0.01）. CONCLUSION： The high sIL-2R level is related to positive anti-HBc in chronic hepatitis B patients. Positive anti-HBc may be related to T-lymphocyte activation and negative anti-HBc may imply immune tolerance in these patients.

Soluble ST2:A new and promising activity marker in ulcerative colitis

AIM:To correlate circulating soluble ST2(sST2) levels with the severity of ulcerative colitis(UC) and serum levels of pro-inflammatory cytokines,and to demonstrate the predictive power of sST2 levels for differentiation between active and inactive UC.METHODS:We recruited 153 patients:82 with UC,26 with Crohn's disease(CD) and 43 disease controls [non-inflammatory bowel disease(IBD)].Subjects were excluded if they had diagnosis of asthma,autoimmune diseases or hypertension.The serum levels of sST2 and pro-inflammatory cytokines [pg/mL;median(25th-75th)] as well as clinical features,endoscopic and histological features,were subjected to analyses.The sST2 performance for discrimination between active and inactive UC,non-IBD and healthy controls(HC) was determined with regard to sensitivity and specificity,and Spearman's rank correlation coefficient(r).To validate the method,the area under the curve(AUC) of receiver-operator characteristic(ROC) was determined(AUC,95% CI) and the total ST2 content of the colonic mucosa in UC patients was correlated with circulating levels of sST2.RESULTS:The serum sST2 value was significantly higher in patients with active [235.80(90.65-367.90) pg/mL] rather than inactive UC [33.19(20.04-65.32) pg/mL],based on clinical,endoscopic and histopathological characteristics,as well as compared with non-IBD and HC(P < 0.001).The median level of sST2 in CD patients was 54.17(35.02-122.0) pg/mL,significantly higher than that of the HC group only(P < 0.01).The cutoff was set at 74.87 pg/mL to compare active with inactive UC in a multicenter cohort of patients.Values of sensitivity,specificity,and ability to correctly classify UC,according to activity,were 83.33%,83.33% and 83.33%,respectively.The AUC of the ROC curve to assess the ability of this molecule to discriminate between active vs inactive UC was 0.92(0.86-0.97,P < 0.0001).The serum levels of sST2 in patients with UC significantly correlated with endoscopic and histo-pathological scores(r = 0.76 and r = 0.67,P < 0.0001,respectively),and with the pro-inflammatory cytokine,tumor necrosis factor-α(r = 0.69 and r = 0.61,respectively,P < 0.0001).Interestingly,we found a direct correlation between total intestinal ST2 content and serum levels of sST2,adjusted to endoscopic activity score in patients with mild(r = 0.44,P = 0.004),moderate(r = 0.59,P = 0.002) and severe disease(r = 0.82,P = 0.002).Only patients with inactive UC showed no significant correlation(r = 0.45,P = 0.267).CONCLUSION:sST2 levels correlated with disease severity and inflammatory cytokines,are able to differentiate active from inactive UC and might have a role as a biomarker.

Early cardiopulmonary resuscitation on serum levels of myeloperoxidase,soluble ST2,and hypersensitive C-reactive protein in acute myocardial infarction patients

BACKGROUND Prompt and effective cardiopulmonary resuscitation(CPR)can promote the recovery of spontaneous circulation to some extent and can save patients’lives.The minimum target of cardiac resuscitation is the restoration of spontaneous circulation(ROSC).However,owing to prolonged sudden cardiac arrest,there is relatively high mortality within 24 h after cardiac resuscitation.Moreover,severe cerebral anoxia can deteriorate the prognosis of patients.Therefore,it is important to adopt an effective clinical evaluation of acute myocardial infarct(AMI)patients’prognosis after cardiac resuscitation for the purpose of prevention and management.AIM To investigate early CPR effects on human myeloperoxidase(MPO),soluble ST2(sST2),and hypersensitive C-reactive protein(hs-CRP)levels in AMI patients.METHODS In total,54 patients with cardiac arrest caused by AMI in our hospital were selected as the observation group,and 50 other patients with AMI were selected as the control group.The differences in serum levels of MPO,sST2,and hs-CRP between the observation group and the control group were tested,and the differences in the serum levels of MPO,sST2,and hs-CRP in ROSC and non-ROSC patients,and in patients who died and in those who survived,were analyzed.RESULTS Serum levels of MPO,sST2,hs-CRP,lactic acid,creatine kinase isoenzyme(CKMB),and cardiac troponin I(cTnI)were significantly higher in the observation group than in the control group(P<0.05).Serum levels of MPO,sST2,hs-CRP,lactic acid,CK-MB,and cTnI in the observation group were lower after CPR than before CPR(P<0.05).In the observation group,MPO,sST2,hs-CRP,lactic acid,CK-MB,and cTnI serum levels were lower in ROSC patients than in non-ROSC patients(P<0.05).MPO,sST2,hs-CRP,and lactic acid serum levels of patients who died in the observation group were higher than those of patients who survived(P<0.05).The areas under receiver operating characteristic curve predicted by MPO,sST2,hs-CRP,lactic acid,CK-MB,and cTnI were 0.616,0.681,0.705,0.704,0.702,and 0.656,respectively(P<0.05).The areas under receiver operating characteristic curve for MPO,SST2,hs-CRP,and lactic acid to predict death were 0.724,0.800,0.689,and 0.691,respectively(P<0.05).Logistic regression analysis showed that MPO,sST2,and hs-CRP were the influencing factors of ROSC[odds ratios=1.667,1.589,and 1.409,P<0.05],while MPO,sST2,hs-CRP,and lactic acid were the influencing factors of death(odds ratios=1.624,1.525,1.451,and 1.365,P<0.05).CONCLUSION Serum levels of MPO,sST2,hs-CRP,and lactic acid have a certain value in predicting recovery and prognosis of patients with ROSC.

Study of the Effect of Leeching on Plasma Endothelin and Soluble Interleukin-2 Receptor in Patients with Systemic Lupus Erythematosus

Objective: to explore the mechanism of leeching in treating systemic lupus erythematosus (SLE). Methods: Forty-four patients with SLE were randomly divided into conventional corticosteroid treated group (control group, n =20) and conventional treatment group with leeching intervention added (leeching group, n =24). Before and after treatment the concentration of plasma endothelin (ET) and soluble interleukin-2 receptor (sIL-2R) were determined. Results: Before treatment the level of plasma ET and sIL-2R in the SLE patients were all higher than those in the normal healthy group, ( P <0.01). But after treatment the level of these in both groups were significantly improved than those of before treatment ( P <0.05), and comparison between these two treated groups showed that the difference between them was significant ( P <0.05). Conclusion: Leeching added to conventional treatment of SLE could be more effective in improving the level of plasma ET and sIL-2R, and ameliorating the impairment of renal tissues.

Elevated pancreatic enzymes, IgM, soluble interleukin-2 receptor in anti-GADab(+) type 1 diabetes

Type 1 diabetes can be classified into immune-mediated diabetes (type 1A) and idiopathic diabetes, which lacks immunological evidence for beta cell autoimmunity (type 1B). Type 1A diabetes is characterized by the presence of the anti-glutamic acid decarboxylase antibody (anti-GADab). Fulminant type 1 diabetes is classified as type 1B diabetes, and characterized by the absence of anti-GADab, flu-like symptoms, and elevated serum exocrine pancreatic enzymes. We report a type 1 diabetic patient who showed flu-like symptoms, elevated serum exocrine pancreatic enzymes, and an extremely high-titer of anti-GADab, manifesting the characteristics of both type 1A and fulminant type 1 diabetes.

Effects of Aprotinin on Serum Interleukin-2 and Soluble Interleukin-2 Receptor during Cardiopulmonary Bypass

Interleukin-2 and its receptor are of importance in regulating immunity responses. The changes of interleukin-2 (IL-2) and soluble interleukin-2 receptor (IL-2R) during heart valve (s) replacement operation and effects of aprotinin on them were observed. Twenty patients undergoing heart valve (s) replacement were randomly divided into two groups: control group (n=10) and apro- tinin group (n=10). In aprotinin group, 1 000 000 KIU aprotinin was given by vein injection and then 2 000 000 KIU was given as a bolus in prime. Blood samples were collected before CPB, right after CPB and on the 1st, 3rd and 7th postoperative day (POD) for serum IL-2 and sIL-2R determination. Results showed that after CPB, IL-2 was reduced and slL-2R increased. Meanwhile, serum IL-2R was lower in aprotinin group than that of control. It is concluded that the immunity depression after CPB is associated with low level of IL-2 and high level of sIL-2R and aprotinin can ameliorate the situation.

Water-soluble lipopolymer delivery of N-methyl-D-aspartic acid receptor 2B siRNA relieves chronic neuropathic pain in rats

Spinal dorsal horn N-Methyl-D-aspartic acid receptor 2B （NR2B） overexpression plays an important role in the production and maintenance of neuropathic pain. Because small interfering RNA （siRNA） can inhibit NR2B expression, siRNA may provide a novel approach to treat neuropathic pain and possibly nerve injury. However, an efficient and safe vector for NR2B siRNA has not been discovered. This study shows that a water soluble lipopolymer （WSLP） comprised of low molecular weight polyethyleneimine （PEI） and cholesterol can deliver siRNA targeting NR2B for the treatment of neuropathic pain. Results show that intrathecal injection of WSLP/siRNA complexes for 3 days inhibit NR2B gene expression with reductions in mRNA and protein levels by 59% and 54%, respectively, compared with control rats （P 〈 0.01）. Injection of WSLP complexed with scrambled siRNA, or PEI with siRNA did not show this inhibitory effect. Moreover, injection of WSLP/siRNA complexes significantly relieved neuropathic pain at 3, 7, 12, and 21 days, while injection of WSLP with scrambled siRNA or PEI with siRNA did not. These results demonstrate that WSLP can efficiently deliver siRNA targeting NR2B in vivo and relieve neuropathic pain.

Administration of soluble activin receptor 2B increases bone and muscle mass in a mouse model of osteogenesis imperfecta

Osteogenesis imperfecta（OI） comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI,many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B（ACVR2B） in a mouse model of type Ⅲ OI（oim）. Treatment of 12-week-old oim mice with ACVR2 B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy,wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system.

Glycosylation-independent binding to extracellular domains 11-13 of mannose-6-phosphate/insulin-like growth factor-2 receptor mediates the effects of soluble CREG on the phenotypic proliferation of vascular smooth muscle cells

Background The present study aimed to investigate the detailed mode and specific sites for their binding as well as the functional relevance of this binding in the phenotypic proliferation of vascular smooth muscle cells(SMCs). Methods CREG knocked-down SMCs were employed to evaluate the biological activity of wtCREG and mCREG.Expressions of SMC differentiation markers SM myosin heavy chain(SM-MHC),SM-actin,heavy caldesmon and myocardin were determined by Western blotting using specific antibodies. Cellular growth of SMCs was assessed by bromide dewuridine (BrdU) incorporation and cell cycle analysis on fluorescence-activated cell sorting(FACS).A solid-phase binding assay was used to study the binding of CREG to extracellular domains of M6P/IGF2R.The cellular co-localization of the two recombinant CREGs with M6P/IGF2R was detected on SMC surface by immunoprecipitation and immunofluorescence analysis.Results The molecular weight of wtCREG was around 30 kD while that of the mCREG was～25 kD.Treatment of wtCREG with PNGase F reduced its molecular weight from～30 kD to～25 kD,whereas PNGase F treatment had no effect on the molecular weight of mCREG.Both wtCREG and mCREG proteins enhanced SMC differentiation,inhibited BrdU incorporation,and arrested cell cycle progression when added to the culture medium.In CREG knocked-down SMCs,the amount of CREG detected by immunoblotting in M6P/IGF2R immunoprecipitates was significantly reduced when compared to normal cells.Both recombinant CREGs co-immunoprecipitated with M6P/IGF2R, although slightly reduced amount of the mutant CREG was detected in M6P/IGF2R immunoprecipitates.Immunostaining revealed that His-tagged CREGs co-localized with IGF2R on the cell surface in a glycosylation-independent manner.In vitro binding assay showed that CREGs bound to M6P/ IGF2R extracellular domains 7-10 and 11-13 in a glycosylation -dependent and -independent manner,respectively.Further blocking experiments using soluble M6P/IGF2R fragments and M6P/IGF2R neutralizing antibody indicated that the biological activities of recombinant CREGs in SMC growth and the up-regulation of SMC differentiation markers were all abolished by treatment with the M6P/IGF2R neutralizing antibody. However,although the growth inhibitory effect of wtCREG was nearly abolished by D7-10 or D11-13,the effect of mCREG was only reversed by Dll-13,indicating that the binding to domains 11-13 is required for CREG to modulate the proliferation of SMCs.Conclusions These data suggest that solubleCREG proteins can exert their biological function via binding to the extracellular domains 7-10 and 11-13 of cell surface M6P/IGF2R in both a glycosylation-dependent and -independent manner.

超声心动图联合sST2、sTREM-1在急性ST段抬高型心肌梗死诊断中的临床价值

目的研究超声心动图指标联合血清可溶性致癌抑制因子2(sST2)、可溶性髓样细胞触发受体-1(sTREM-1)在急性ST段抬高型心肌梗死(STEMI)诊断中的临床价值。方法选取2021年9月至2022年9月在河北省沧州中西医结合医院治疗的90例急性STEMI患者作为STEMI组,选取同期冠状动脉造影检查结果为阴性的90例胸痛患者为对照组,比较两组超声心动图指标左室射血分数(LVEF)、左室舒张末期内径(LVEDD)和血清sST2、sTREM-1水平;采用Pearson相关分析急性STEMI患者LVEF、LVEDD与血清sST2、sTREM-1水平的相关性。采用受试者工作特征(ROC)曲线分析血清sST2、sTREM-1、LVEF、LVEDD诊断急性STEMI的价值。采用多因素Logistic回归分析急性STEMI发生的影响因素。结果STEMI组LVEF低于对照组,LVEDD高于对照组,差异均有统计学意义(P<0.05)。STEMI组CK-MB、cTnI水平及心率、心绞痛史比例高于对照组,差异均有统计学意义(P<0.05)。Pearson相关分析结果显示,急性STEMI患者LVEF与血清sST2、sTREM-1水平均呈负相关(r=-0.454、-0.463,P<0.05),LVEDD与血清sST2、sTREM-1水平均呈正相关(r=0.493、0.515,P<0.05)。LVEF、LVEDD及血清sST2、sTREM-1联合诊断急性STEMI的曲线下面积(AUC)为0.930,明显大于各项指标单独检测的AUC(Z=4.780、5.611、3.591、3.087,P<0.05)。多因素Logistic回归分析结果显示,sST2≥24.91 ng/mL、sTREM-1≥36.65 pg/mL是急性STEMI发生的危险因素(P<0.05)。结论血清sST2、sTREM-1联合超声心动图对急性STEMI患者的诊断效能较好。

Soluble Interleukin 2 Receptor-Alpha (sIL-2Rα) in the Peripheral Blood of Dogs—Comparison of Malignant Neoplasia with Other Diseases

Background: Cytokines are mediators of diseases. Expression levels in the blood could be of clinical relevance. Objective: sIL-2Rα is used as a marker for different malignancies in human medicine. The aim of this study was to show if sIL-2Rα is detectable and if there is any correlation to different diseases in dogs. Methods: For this purposes sIL-2Rα concentrations in the blood were measured in healthy dogs, in dogs with different non-neoplastic diseases and benign tumors and in dogs with malignant tumors. Serum levels of sIL-2Rα were measured by using a human specific enzyme linked immunosorbent assay (ELISA). Results: Measurement of sIL-2Rα was successful in most of the samples. Dogs with diseases have significantly increased serum levels of sIL-2Rα compared to healthy controls. sIL-2Rα serum levels are higher in patients with non-neoplastic diseases and benign tumors than in those with malignant neoplasia. There is a strong correlation between sIL-2Rα and leukocyte count. Conclusion: Measurements of sIL-2Rα in serum may be helpful in detecting stages and grades of inflammation in the progression of disease. sIL-2Rα could actually not be used as an indicator for malignant diseases in dogs like in humans. The strong correlation between sIL-2Rα and the leukocyte count indicates the inflammatory response to the disease. This could be helpful in giving a prognosis in some cases, because the inflammatory reaction is of prognostic relevance in different diseases including malignant and non-malignant neoplasia. Although the results of our research studies were very promising, further studies should be performed with a canine ELISA.

Constitutively Active Soluble Form of Erythropoietin Receptor Suppresses Growth and Angiogenesis of Xenografts of Transfected Cancer Cell Lines

We examined the effect of blocking the erythropoietin (Epo) signaling using an anti-Epo antibody, soluble form of Epo receptor (sEpoR) capable of binding to Epo or EpoR antagonist, and proved to be effective against xenografts of female reproductive organ malignancies and of cancer cell lines in nude mice. We transfected seven cancer cell lines of various origins to express constitutively active sEpoR, and examined their tumorigenesis in nude mice. Suppression of the tumor growth, decrease in viable and proliferating cells and reduction of vascular density were seen individually in all xenografts of transfected cell lines compared with the controls. Quantitative RT-PCR analyses showed that expression levels of Epo, EpoR, ?1A-adrenaline receptor (?1A-ADR) and muscalinic acetylcholine receptor subunit 3 mRNAs (m3-AchR) were higher in the majority of the wild-type xenografts than in the corresponding cell lines except for A549. In some of the transfected xenografts, EpoR, ?1A-ADR and m3-AchR mRNAs were down-regulated. Western blot analyses revealed that the constitutively activated ERK1/2MAPK was discernible in the majority of non-transfected cell lines and was reduced in the transfected cell lines. However, it was regained after exposure to acetylcholine and/or noradrenaline. These findings suggest that constitutively active sEpoR can effectively destroy the xenografts but signals from the autonomic neurotransmitters of the host produced under stress may interfere with this antitumor activity.

DETECTION OF PLASMA SOLUBLE INTERLEUKIN－2 RECEPTOR IN PATIENTS WITH SEVERE AND CHRONIC ACTIVE HEPATITIS B

Plasma levels of soluble interleukin-2 receptor (sIL-2R) in patients with chronic active hepatitis B (CAHB) or severe hepatitis B (SHB) were measured quantitatively by 'sandwich' ELISA with monoclonal antibodies in order to explore the change of sIL-2R levels, its clinical significance,and its relation to liver damage. The results showed that the plasma sIL-2R levels in patients with CAHB and SHB were much higher than those in normal controls (P < 0. 01 ), and the level ofplasma sIL-2R in patients with SHB was greatly higher than that in patients with CAHB. These results suggest that there is close relation between plasma level of sIL-2R, the clinical types of hepatitis B,and the severity of liver damage. In addition, there is no significant difference in plasma levels of sIL-2R between acute severe hepatitis B (ASHB), subacute severe hepatitis B (SASHB), and chronic severe hepatitis B (CSHB). No relation was found between sIL-2R level and hepatitis B virusreplication activity.

经皮冠状动脉介入治疗急性心肌梗死患者的sST2对冠状动脉侧支循环形成的预测价值

目的经皮冠状动脉介入治疗急性心肌梗死患者的可溶性致癌抑制因子2(Soluble suppression of tumorigenesis 2,sST2)对冠状动脉侧支循环形成的预测价值。方法我们纳入2020年6月至2023年7月我院收治的85例行急诊PCI(Percutaneous coronary intervention)的ST段抬高型心肌梗死(ST elevation myocardial infarction,STEMI)患者作为研究对象,入院后患者均根据最新急性ST段抬高型心肌梗死治疗指南行急诊PCI术,通过标准血管造影在基线时收集冠状动脉侧支循环(Collateral circulation,CC)数据。根据Rentrop分级法对侧支循环进行分级:没有填充任何血管等级为0,小侧支充填为1级,部分心外膜动脉充盈为2级,完全心外膜动脉灌注为3级。其中0级和1级被视为侧支循环形成不良,2级和3级被视为侧支循环形成良好。患者被分为两组:CC良好组(n=33)和CC不良组(n=52)。急性心肌梗死患者入院第一天介入术前用ELISA法测定血清sST2,所有患者均行急诊PCI术。对比CC形成良好组与CC形成不良组的一般资料,用Logistic回归分析危险因素,以受试者工作特征(ROC)曲线下面积(AUC)分析入院时血清sST2水平,以及对STEMI患者侧支循环的预测价值。结果通过回顾性分析发现,85例患者中冠状动脉侧支循环形成良好33例,冠状动脉侧支循环形成不良52例,冠脉侧支循环形成率38%。冠状动脉侧支循环形成不良组血清sST2浓度高于侧支循环形成良好组,差异有统计学意义(P<0.05);入院sST2预测STEMI患者急诊PCI术后侧支循环的ROC曲线下面积为0.706(95%CI:0.579~0.833,P<0.05)。结论s ST2水平对STEMI患者冠状动脉侧支循环形成具有良好的预测价值。

sST2在急性ST段抬高心肌梗死患者中的表达及对预后的影响

目的探讨血清可溶性生长刺激表达基因2蛋白(sST2)在急性ST段抬高心肌梗死(STEMI)患者中的表达及对预后的影响。方法回顾性选取2020年1月至2022年4月在金华市中心医院心内科住院治疗的急性STEMI患者142例(STEMI组),另择非冠心病及心力衰竭患者72例作为对照(对照组)。采用酶联免疫吸附法测定并比较两组血清sST2水平。观察1年内的主要不良心血管事件(MACE),并分为MACE组和非MACE组,分析MACE的危险因素及sST2对MACE的预测价值。结果STEMI组sST2水平36.80(19.31,66.47)ng/mL,高于对照组的12.20(9.11,15.66)ng/mL(P<0.001);二元logistic回归显示sST2是MACE发生的危险因素(OR=1.032,95%CI 1.001~1.063,P=0.040),sST2预测1年内发生MACE的AUC为0.815,截断值为45.969 ng/mL,灵敏度为0.844,特异度为0.736。结论sST2与STEMI发病相关,并可预测STEMI患者1年内的MACE。