IL-1β,IL-6,IFN-γ在甲型H1N1流感病毒性肺炎患者血清中的表达及其与疾病预后的相关性分析

目的探讨白细胞介素(IL)-1β、IL-6、γ干扰素(IFN)-γ在甲型H1N1流感病毒性肺炎患者血清中的表达及其与疾病预后的相关性。方法选取2017年1月-2019年1月本院收治的128例确诊甲型H1N1流感病毒性肺炎患者,将其分为重症组(96例)和轻症组(32例),另选取同期来本院进行健康体检的40例受试者为健康组,比较3组患者血清IL-1β、IL-6、IFN-γ水平;根据病情转归分为存活组和死亡组,比较2组血清IL-1β、IL-6、IFN-γ水平及其他可能影响预后的因素,采用logistic回归分析法明确影响预后的危险因素。结果与健康组比较,重症组、轻症组血清IL-1β,IL-6,IFN-γ水平均较高,且重症组高于轻症组,差异均有统计学意义(P0.05)。死亡组患者体质量指数、血清乳酸脱氢酶及血清IL-1β,IL-6,IFN-γ水平均高于存活组,而外周血淋巴细胞计数低于存活组,差异均有统计学意义(P0.05)。经Logistic回归分析,体质量指数、外周血淋巴细胞计数、血清乳酸脱氢酶及血清IL-1β,IL-6,IFN-γ水平均是导致甲型H1N1流感病毒性肺炎患者预后不良的危险因素(OR=2.134、1.689、3.725、2.351,2.535,P均0.05)。结论血清IL-1β,IL-6,IFN-γ水平与甲型H1N1流感病毒性肺炎严重程度及预后关系密切,早期进行相应检查对判断疾病转归有重要价值。     

血清IGF-1, IGFBP-3, PSA及fPSA在前列腺癌诊断中的意义

目的探讨胰岛素样生长因子-1（IGF-1）和胰岛素样生长因子结合蛋白-3（IGFBP-3）在前列腺癌（PCa）患者血清中的水平及其与前列腺特异抗原（PSA）、游离PSA（fPSA）联合检测的意义。方法采用化学发光法（CLIA）检测52例PCa患者、48例良性前列腺增生症（BPH）患者和48例健康对照者的血清IGF-1,IGFBP-3,PSA及fPSA水平。结果 PCa组IGF-1水平较BPH组、健康对照组明显升高（P＜0.01）,BPH组与健康对照组比较,差异无统计学意义（P＞0.05）;PCa组IGFBP-3水平低于BPH组和健康对照组（P＜0.01）,BPH组与健康对照组比较,差异有统计学意义（P＜0.01）。IGF-1及IGFBP-3诊断PCa的灵敏度分别为83.6%和76.4%,特异度分别为84.0%和74.0%,阳性预测值分别为85.2%和76.4%,阴性预测值分别为82.4%和74.0%。血清IGF-1与PSA或fPSA联合检测可明显提高诊断PCa的灵敏度。结论 PCa患者的IGF-1及IGFBP-3水平较健康对照者发生改变,IGF-1与PSA或fPSA联合检测更有助于PCa的诊断。     

疏血通注射液对冠心病糖尿病病人血浆ET-1,ICAM-1,TNF-α和P-选择素水平的研究

目的观察疏血通注射液对冠心病合并糖尿病病人血浆内皮素-1（ET-1）、细胞间黏附分子-1（ICAM-1）、肿瘤坏死因子-α（TNF-α）和P-选择素水平的影响,研究疏血通注射液保护血管内皮细胞,延缓动脉粥样硬化过程的作用。方法将确诊为冠心病合并糖尿病的60例病人随机分为治疗组与对照组,每组30例。对照组予常规治疗,治疗组在对照组治疗的基础上加用疏血通注射液6mL静脉输注,每日1次。两组均以2周为1个疗程,观察治疗前后4项指标的变化。结果治疗组治疗前后自身及与对照组治疗后比较,4项指标均明显下降,具有统计学意义（P〈0.05或P〈0.01）。结论疏血通注射液能显著降低与血管内皮损伤、血小板聚集及炎症反应密切相关的细胞因子水平,起到保护血管内皮细胞的功能,有延缓细胞因子介导的动脉粥样硬化过程的作用。     

HLA-ABC,HLA-DR,ICAM-1在乙型肝炎肝细胞表达的意义

为进一步探讨HLA-ABC.HIA-DR.ICAM-1在乙型肝炎肝细胞损伤中的作用.利用标记链菌素亲生物蛋白(LSAB)法对98例乙型肝炎肝穿组织进行HLA-ABC,HLA-DR,ICAM-1检测。结果显示HLA-ABC,ICAM-1在乙型肝炎肝细胞存在广泛表达,且与肝脏病变程度有关,HLA-DR也有一定程度表达,其阳性率分别为85.7％,83.7％,26.5％。阳性表达多位于肝细胞炎性病变或坏死区,常伴有不同程度炎性细胞浸润。提示HLA-ABC,ICAM-1的在肝细胞广泛表达在乙型肝炎发病中起重要作用。HLA-DR异常表达也一定程度参与了乙肝发病。这些免疫有关分子为T淋巴细胞识别杀伤HBV感染肝细胞提供了必要的分子基础,不仅与乙型肝炎肝细胞损伤有关,而且对肝内病毒的清除可能有一定的作用。     

慢性乙型肝炎血清MMP-1,MMP-2,SOD与纤维化四项分析的临床研究

目的目的研究金属基质蛋白酶-1（MMP-1）,金属基质蛋白酶-2（MMP-2）,超氧化物歧化酶（SOD）与纤维化四项在慢性乙肝患者血清中的表达,动态变化及相关性的分析。方法选择我院住院慢乙肝患者127例,检测肝纤维化四项、SOD、MMP1、MMP2。结果随着肝脏炎症程度和纤维化程度的增加,血清MMP1的值越来越降低,肝硬化组与慢轻组比较,P〈0.05;MMP2的值则越来越高,肝硬化组与慢轻组比较,P〈0.01,呈正相关;SOD的值也越来越高,肝硬化组与慢轻组比较,P〈0.05。结论MMP1,MMP2,SOD对评价肝脏炎症程度及纤维化程度有一定意义。     

血清TPS,CEA,CYF RA2 1-1,NSE联合检测对肺癌的诊断价值

目的探讨血清TPS、CEA、CYFR A21-1、NSE联合检测对肺癌的诊断价值。方法采用ELISA法及电化学发光法对72例肺癌（其中鳞癌30例,腺癌2 8例,小细胞癌14例）患者血清TPS、CEA、CYFRA21-1和NSE水平进行检测,并与42例肺部良性病患者和30例健康人血清进行分析。结果肺癌患者血清4种肿瘤标志物含量明显高于肺部良性疾病组（P〈0.001）和健康对照组（P〈0.001）。4种肿瘤标志物单项检测时,特异度较高（76.4%-91.5%）,但敏感度不是很高（45.8%-83.3%）。联合检测后,可提高肺癌的阳性检出率（100%）。结论 TPS、CEA、CYFRA21-1和NSE对肺癌有一定的辅助诊断价值,且CEA、NSE和CYFRA21-1对不同组织类型肺癌均有一定诊断价值,联合检测可提高对肺癌的阳性诊断。     

大肠癌组织Ets-1,MMP-1和VEGF的表达及意义

目的:检测大肠癌中转录因子Ets-1,基质金属蛋白酶-1(MMP-1)和血管内皮生长因子(VEGF)的表达,探讨Ets-1在大肠癌血管生成和浸润转移中的作用.方法:应用免疫组化SP法检测61例大肠癌组织和21例正常大肠组织中Ets-1,MMP-1和VEGF蛋白的表达水平.结果:Ets-1,MMP-1和VEGF在正常大肠黏膜中表达均为阴性.在大肠癌组织中表达的阳性率分别为75.4%,78.7%和82.0%.其表达水平与肿瘤大小和分化程度无关(P>0.05),与Duke's分期(χ2=10.718,P<0.01;χ2=8.323,P<0.01;χ2=6.145,P<0.05)、浸润深度(χ2=7.705,P<0.01;χ2=19.101,P<0.01;χ2=14.707,P<0.01)、淋巴结转移(χ2=9.333,P<0.01;χ2=3.965,P<0.05;χ2=4.638,P<0.05)和远处转移(χ2=5.472,P<0.05;χ2=4.125,P<0.05;χ2=5.034,P<0.05)密切相关.在大肠癌中,Ets-1的表达与MMP-1和VEGF的表达呈正相关(r=0.447,P<0.01;r=0.425,P<0.05).结论:Ets-1在大肠癌中高表达,与临床分期、浸润深度、转移密切相关.Ets-1的表达与MMP-1和VEGF的表达呈正相关,三者的表达水平可作为判定大肠癌恶性生物学行为的参考指标.     

TNF-α,Ang-1,IL-8在COPD合并肺动脉高压发病机制中的作用

目的研究肿瘤坏死因子α（TNF-α）、血管生成素-1（Ang-1）、白介素-8（IL-8）在COPD合并肺动脉高压发病机制中的意义。方法选取呼吸内科40名COPD患者,分为两组,B组：20名（GOLDⅡ级COPD合并肺动脉高压患者）;C组：20名（GOLDⅢ级COPD合并肺动脉高压患者）。各组样本行心脏彩超检查确定肺动脉高压并估算肺动脉高压数值,取血清用酶联免疫法测定TNF-α、Ang-1、IL-8数值,并且各组样本行肺功能检查。结果各组中的Ang-1、TNF-α、IL-8相比较有统计学意义（P〈0.05）,Ang-1与肺动脉压负相关（P〈0.05）、TNF-α与肺动脉高压存在正相关（P〈0.05）,肺功能与肺动脉压存在负相关（P〈0.05）。结论 COPD合并肺动脉高压患者与血管因素及炎症因素均有关系,与血管因素较为密切。     

Prognostic and clinicopathological features of E-cadherin, α-catenin,β-catenin, γ-catenin and cyclin D1 expression in human esophageal squamous cell carcinoma

AIM: To investigate the expression of E-cadherin, α-catenin,β-catenin, γ-catenin and cyclin D1 in patients with esophageal squamous cell carcinoma (ESCC), and analyze their interrelationship with clinicopathological variables and their effects on prognosis. METHODS: Expression of E-cadherin, α-catenin, β-catenin, γ-catenin and cyclin D1 was determined by EnVision or SABC immunohistochemical technique in patients with ESCC consecutively, their correlation with clinical characteristics was evaluated and analyzed by univariate analysis. RESULTS：The reduced expression rate of E-cadherin, α-catenin, β-catenin and γ-catenin was 88.7%, 69.4%, 35.5% and 53.2%, respectively. Cyclin D1 positive expression ratewas 56.5%. Expression of γ-catenin was inversely correlated with the degree of tumor differentiation and lymph node metastasis (x^2=4.183 and x^2=5.035, respectively, P&lt;0.05), whereas the expression of E-cadherin was correlated only with the degree of differentiation (x^2=5.769, P&lt;0.05). Reduced expression of E-cadherin and γ-catenin was associated with poor differentiation of tumor, reduced expression of γ-catenin was also associated with lymph node metastasis. There obviously existed an inverse correlation between level of E-cadherin and γ-catenin protein and survival. The 3-year survival rates were 100% and 56% in E-cadherin preserved expression group and inreduced expression one and were 78% and 48% in γ-catenin preserved expression group and in reduced expression one, respectively. The differences were both statistically significant. Correlation analysis showed the expression level of α-catenin correlated with that of E-cadherin and β-catenin (P&lt;0.05). CONCLUSION: The reduced expression of E-cadherin and γ-catenin, but not α-catenin, β-catenin and cyclin D1, implies more aggressive malignant behaviors of esophageal carcinoma cells and predicts the poor prognosis of patients.     

RECK,MMP-9及TGF-β1在胃癌组织中的表达及其相互关系

目的:研究RECK,MMP-9和TGF-β1在胃癌及正常胃组织中的表达,探讨其在胃癌的发生、发展、浸润和转移中的作用.方法:选择临床及病理资料齐全的存档胃腺癌蜡块标本54例,另取正常胃黏膜标本15例作对照.采用第二代通用型二步法监测系统(PV-9000)免疫组化方法检测RECK,MMP-9及TGF-β1在胃癌及正常胃组织中的表达.结果:RECK在胃癌组织中低表达(51.9%),并随肿瘤浸润深度的加深、淋巴转移的产生、远隔转移的发生、临床分期的提高、肿瘤病理分化程度的降低而降低(P<0.05).MMP-9在胃癌组织中高表达(75.9%),并随肿瘤浸润深度的加深、淋巴转移的产生、临床分期的提高、肿瘤病理分化程度的降低而增高(P<0.05).TGF-β1在胃癌组织中高表达(77.8%),并随淋巴转移的产生、临床分期的提高、肿瘤病理分化程度的降低而增高(P<0.05).胃癌组织中RECK与MMP-9、TGF-β1的表达呈负相关(r=-0.618,P<0.001;r=-0.620,P<0.001),MMP-9与TGF-β1的表达呈正相关(r=0.716,P<0.001).结论:胃癌组织中RECK低表达,MMP-9,TGF-β1高表达.RECK,MMP-9及TGF-β1可以作为评估胃癌发生浸润转移的重要指标.     

Effect of pegylated interferon alpha 2b plus ribavirin treatment on plasma transforming growth factor-β1,metalloproteinase-1, and tissue metalloproteinase inhibitor-1 in patients with chronic hepatitis C

AIM: To evaluate the effect of antiviral treatment on plasma levels of transforming growth factor-β1 (TGF-β1),metalloproteinase 1 (MMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in patients with chronic hepatitis C.METHODS: TGF-β1, MMP-1, and TIMP-1 plasma concentrations were measured by an enzyme immunoassay in 28 patients, during 48 wk of treatment with pegylated interferon-alpha 2b (PEG-IFN-α2b) plus ribavirin (RBV)and after 24 wk of follow-up. Patients were divided into two groups: responders (R) and non-responders (NR)related to achieved sustained virologic response. Normal values were evaluated in plasma samples of 13 healthy volunteers.RESULTS: Baseline plasma concentrations of TGF-β1and TIMP-1 (30.9±3.7 and 1506±61 ng/mL respectively)measured in all subjects significantly exceeded the normal values (TGF-β1:18.3±1.6 ng/mL and TIMP-1:1102±67 ng/mL). In contrast, pretreatment MMP-1mean level (6.5±0.9 ng/mL) was significantly lower than normal values (11.9±0.9 ng/mL). Response to the treatment was observed in 12 patients (43%). TGF-β1mean concentration measured during the treatment phase decreased to the control level in both groups.However at wk 72, values of NR patients increased and became significantly higher than in R group.TIMP-1 concentrations in R group decreased during the treatment to the level similar to normal. In NR group,TIMP-1 remained significantly elevated during treatment and follow-up phase and significant difference between both groups was demonstrated at wk 48 and 72. MMP-1levels were significantly decreased in both groups at baseline. Treatment caused rise of its concentration only in the R group, whereas values in NR group remained on the level similar to baseline. Statistically significant difference between groups was noted at wk 48 and 72.CONCLUSION: These findings support the usefulness of TGF-β1, TIMP-1, and MMP-1 in the management of chronic hepatitis C. Elevated TIMP-1 and low MMP-1plasma concentrations during antiviral therapy may indicate medication failure.     

Effect of lamivudine treatment on plasma levels of transforming growth factor β1, tissue inhibitor of metalloproteinases-1 and metalloproteinase-1 in patients with chronic hepatitis B

AIM: Transforming growth factor (TGF)-β1, metalloproteinase (MMP)-1 and its tissue inhibitor (TIMP)-I are considered predictive biomarkers of chronic hepatitis activity and fibrosis.The aim of this study was to evaluate the effect of lamivudine treatment on the plasma levels of these peptides in patients with chronic hepatitis B.METHODS: TGF-β1, MMP-1 and TIMP-1 plasma concentrations were measured with an enzyme immunoassay in 40 patients treated with lamivudine for 48 wk. Elimination of HBV-DNA and HBV antigens was evaluated 24 wk after treatment completion.RESULTS: Baseline TGF-β1(29.6&#177;2.2 ng/mL) and TIMP-1(1 578&#177;93 ng/mL) significantly exceeded normal values(18.3&#177;1.6 ng/mL and 1 102&#177;67 ng/mL respectively). Lamivudine treatment resulted in a significant decrease of TGF-β1 and TIMP-1 during treatment with an increase after 24 wk of treatment. Pretreatment MMP-1 levels (6.7&#177;0.7 ng/mL) were significantly lower than normal values (11.9&#177;0.9 ng/mL) and increased during treatment and follow-up. A significant correlation was noted between TGF-β1 or TIMP-1 and aminotransferases as well as fibrosis scored in liver biopsy specimens. There were no statistically significant differences of TGF-β1, TIMP-1 and MMP-1 between four groups at baseline, 24 and 48 wk of treatment. TGF-β1 and TIMP-1 levels increased significantly in non-responders and normalized in responders at wk 72. MMP-1 also normalized in responders and decreased to values significantly lower than normal in non-responders.CONCLUSION: These findings support the role of TGF-β1,TIMP-1 and MMP-1 in the pathogenesis of chronic hepatitis B.Because of their association with hepatic injury and antiviral treatment efficacy, determination of these peptides may be useful in disease management.     

Effect of lamivudine treatment on plasma levels of transforming growth factor β1, tissue inhibitor of metalloproteinases-1 and metalloproteinase-t in patients with chronic hepatitis B

AIM: Transforming growth factor (TGF)-β1, metalloproteinase(MMP)-1 and its tissue inhibitor (TIMP)-1 are consideredpredictive biomarkers of chronic hepatitis activity and fibrosis. The aim of this study was to evaluate the effect of lamivudine treatment on the plasma levels of these peptides in patients with chronic hepatitis B.METHODS: TGF-β1, MMP-1 and TIMP-1 plasma concentrations were measured with an enzyme immunoassay in 40 patients treated with lamivudine for 48 wk. Elimination of HBV-DNAand HBV antigens was evaluated 24 wk after treatment completion.RESULTS: Baseline TGF-β1 (29.6±2.2 ng/mL) and TIMP-1(1 578±93 ng/mL) significantly exceeded normal values(18.3±1.6 ng/mL and 1 102±67 ng/mL respectively). Lamivudine treatment resulted in a significant decrease of TGF-β1 andTIMP-1 during treatment with an increase after 24 wk oftreatment. Pretreatment MMP-1 levels (6.7±0.7 ng/mL) weresignificantly lower than normal values (11.9±0.9 ng/mL) and increased during treatment and follow-up. A significant correlation was noted between TGF-β1 or TIMP-1 and aminotransferases as well as fibrosis scored in liver biopsy specimens. There were no statistically significant differences of TGF-β1, TIMP-1 and MMP-1 between four groups atbaseline, 24 and 48 wk of treatment. TGF-β1 and TIMP-1 levels increased significantly in non-responders and normalized in responders at wk 72. MMP-1 also normalized in responders and decreased to values significantly lower than normal innon-responders.CONCLUSION: These findings support the role of TGF-β1,TIMP-1 and MMP-1 in the pathogenesis of chronic hepatitis B.Because of their association with hepatic injury and antiviral treatment efficacy, determination of these peptides may be useful in disease management.     

Elevated matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in obese children and adolescents

Matrix metalloproteinases (MMPs) have been implicated in the atherosclerotic process and risk factors for the disease such as hypertension, hyperlipidemia, or diabetes mellitus in adults. So far, circulating levels of MMPs and their tissue inhibitors (TIMPs) have not been assessed in children and adolescents with obesity, a known risk factor for cardiovascular disease. Plasma levels of MMP-9 and TIMP-1 were measured immunoenzymatically in 45 obese children and adolescents, aged 15 +/- 1.8 years. The control group consisted of 28 healthy children, aged 14.5 +/- 2.5 years. MMP-9 and TIMP-1 concentrations were higher in obese children than in the control group (MMP-9: 553.5 +/- 311 vs 400.4 +/- 204 ng/mL, respectively; P = .02; TIMP-1: 161.2 +/- 32 vs 143.1 +/- 20.1 ng/mL, respectively; P = .03). We found significantly higher levels of MMP-9 in obese children with coexisting hypertension than in obese normotensive patients (635 +/- 308 vs 450 +/- 289 ng/mL, respectively; P = .04). MMP-9 correlated with body mass index (BMI) (r = 0.33, P = .005) and fasting insulin (r = 0.3, P = .013); TIMP-1 correlated with BMI (r = 0.35, P = .006). In the group of obese hypertensive children (n = 25), MMP-9 correlated with BMI (r = 0.41, P = .001), systolic blood pressure (r = 0.41, P = .002), fasting insulin (r = 0.37, P = .006), and homeostasis model assessment index of insulin resistance (r = 0.27, P = .03). TIMP-1 correlated with BMI (r = 0.33, P = .025) and systolic (r = 0.38, P = .008) and diastolic (r = 0.47, P = .001) blood pressure. In the regression models, MMP-9 was found to be dependent on fasting insulin (R(2) = 0.16, P = .04), and TIMP-1 on BMI (R(2) = 0.14, P = .04). In the obese hypertensive group, TIMP-1 was dependent on diastolic blood pressure (R(2) = 0.18, P = .04). Obese children and adolescents have elevated plasma concentrations of MMP-9 and TIMP-1. Coexistence of hypertension may exacerbate alterations of extracellular matrix turnover in these patients. It might be hypothesized that elevated MMP and TIMP concentrations may be related to increased cardiovascular risk in obese and particularly in obese hypertensive children and adolescents.     

Plasma matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 as biomarkers of ulcerative colitis activity

AIM: Overexpression of mucosal metalloproteinases (MMP) has been demonstrated recently in inflammatory bowel disease. Their activity can be counterbalanced by the tissue inhibitor of metalloproteinases (TIMP). The aim of this study was to evaluate the effect of ulcerative colitis (UC) on MMP-1 and TIMP-1 plasma concentrations, as two possible biomarkers of the disease activity. METHODS: MMP-1 and TIMP-1 plasma concentrations were measured with an enzyme immunoassay in 16 patients with endoscopically confirmed active UC. RESULTS: Plasma concentrations of both MMP-1 (13.7 +/- 0.2 ng/ml) and TIMP-1 (799 +/- 140 ng/ml) were significantly elevated in UC patients in comparison to healthy controls (11.9 +/- 0.9 ng/ml and 220 +/- 7 ng/ml respectively). There was no correlation between TIMP-1 and MMP-1 concentrations (r=-0.02). TIMP-1 levels revealed significant positive correlations with scored endoscopic degree of mucosal injury, disease activity index and clinical activity index values as well as C-reactive protein concentration. There was no correlation between MMP-1 and laboratory, clinical or endoscopic indices of the disease activity. CONCLUSION: These results confirm the role of both MMP-1 and TIMP-1 in the pathogenesis of ulcerative colitis. However only TIMP-1 can be useful as a biomarker of the disease activity, demonstrating association with clinical and endoscopic pictures.     

Circulating biochemical marker levels of collagen metabolism are abnormal in patients with abdominal aortic aneurysm

Changes in extracellular matrix composition induced by abnormal collagen metabolism in the aortic wall may be an important factor in the progression of aortic structural changes. The authors have measured several types of biochemical marker for collagen metabolism in plasma: carboxyterminal propeptide of type Icollagen (PICP) for a pure collagen synthesis marker, matrix metalloproteinase-1 (MMP-1) for a degradation marker of collagen matrix, and tissue inhibitors of metalloproteinase-1 (TIMP-1) as a native inhibitor of MMP-1. Subjects of this study were 17 patients with abdominal aortic aneurysm (AAA), 14 patients with atherosclerosis obliterans (ASO), and 22 age/sex-matched healthy controls (HC). Blood samples were drawn from a forearm vein and measured by radioimmunoassay or enzyme-linked immunosorbent assay. Plasma concentrations of PICP in patients with AAA were significantly decreased compared to those in HC patients (82.0 +/- 16.4 vs 111.3 +/- 40.3 ng/mL; p < 0.01), but those in patients with ASO (105.4 +/- 55.4 ng/mL) were comparable to control concentrations. Although no differences in plasma concentrations of MMP-1 were observed among the three subject groups (HC, 20.0 +/- 5.6 ng/mL; ASO, 21.4 +/- 13.8 ng/mL; AAA, 24.5 +/- 11.7 ng/mL; NS), MMP-1/PICP ratio as an index of collagen degradation to collagen neosynthesis in AAA was significantly elevated compared to HC (0.32 +/- 0.18 vs 0.20 +/- 0.08; p < 0.01). Plasma concentrations of TIMP-1 in patients with AAA (293.8 +/- 61.2 ng/mL) or ASO (327.6 +/- 54.9 ng/mL) were significantly higher than in HC (227.3 +/- 60.2 ng/mL; both p < 0.01). In conclusion, these data suggest that although a compensatory mechanism such as increased TIMP-1 may be activated, collagen neosynthesis may decrease with relatively increased collagen degradation in patients with AAA.     

Increased circulating matrix metalloproteinase-2 in patients with hypertrophic cardiomyopathy with systolic dysfunction.

BACKGROUND: Some patients with hypertrophic cardiomyopathy (HCM) develop left ventricular (LV) wall thinning associated with LV dilatation and systolic dysfunction. Recently, matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) were reported to be involved in ventricular remodeling, however, little is known about MMPs and TIMPs in patients with HCM. METHODS AND RESULTS: Enzyme-linked immunoassays were used to measure the plasma concentrations of MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 in 11 patients with HCM accompanied by systolic dysfunction (fractional shortening (FS) <25%, group A), 17 patients with HCM who had preserved systolic function (FS> or =25%, group B), and 50 age-matched clinically healthy control subjects (mean age: 57 years). The concentration of MMP-2 in group A was significantly higher than in group B and the control subjects (1,124 +/- 84, 792 +/- 49, 809 +/- 26 ng/ml, respectively), whereas there was no significant difference between group B and the control subjects. MMP-2 concentrations significantly increased as the New York Heart Association functional class increased in patients with HCM. TIMP-2 was also significantly higher in group A patients than in group B and the control subjects (45.3 +/- 4.7, 34.6 +/- 2.2, 33.7 +/- 1.8 ng/ml, respectively), but there was no difference between group B and control subjects. TIMP-1 was significantly higher in HCM patients than in control subjects. MMP-3 and MMP-9 concentrations did not differ among the 3 groups. Both MMP-2 and TIMP-2 correlated significantly with FS and LV dimension, negatively and positively, respectively. CONCLUSIONS: These results suggest that changes in the release and activity of MMP-2 and TIMP-2 may be associated with the mechanisms responsible for cardiac remodeling in patients with HCM.     

细胞因子在类风湿关节炎患者肺间质病变中的意义

目的 探讨类风湿关节炎(RA)继发间质性肺疾病(RA-ILD)患者血清基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织抑制因子(TIMP-1)和转化生长因子β,(TGF-β1)的变化及其意义.方法 RA组29例,RA-ILD组28例(其中早期RA-ILD组16例,中晚期RA-ILD组12例),对照组为健康体检人员29名.采用ELASA法检测血清中MMP-9、TIMP-1和TGF-β1水平.计量资料用-x±s表示,多组间比较采用方差分析,两组间比较采用t检验,关节分级资料采用卡方检验.结果 RA组和RA-ILD组血清TIMP-1水平[(645±220)和(536±188)μg/L]明显高于对照组[(392±92)μg/L],RA-ILD组血清TGF-β1.水平[(13.1±10.0)μg/L]明显高于RA组和对照组[(3.9±2.9)和(2.4±1.7)μg/L],RA组与RA-ILD组血清TIMP-1水平、RA组与对照组血清TGF-β1的水平无明显差别.各组血清MMP-9水平和MMP-9/TIMP-1均无明显差别.中晚期RA-ILD组血清TIMP-1水平[(690±110)μg/L]明显高于早期RA-ILD组[(420±147)μg/L],中晚期RA-ILD组血清TGF-β1水平[(17.9±8.2)μg/L]明显高于早期RA-ILD组[(9.5±9.9)μg/L].中晚期RA-ILD组血清MMP-9/TIMP-1(0.9±0.1)明显低于早期RA-ILD组(1.2±0.4).早期RA-ILD组血清MMP-9水平[(537±309)μg/L]与中晚期RA-ILD组[(595±110)μg/L]无明显差别.结论 血清TGF-β1可以作为RA患者ILD的诊断标志,且在一定程度上可反映RA-ILD肺部病变的严重程度.MMP-9/TIMP-1下降能反映肺部病变的严重程度.血清MMP-9水平不能作为RA-ILD的诊断指标及ILD肺部病变严重程度的判定指标.     

Matrix-metalloproteinases and their inhibitors are elevated in severe sepsis: prognostic value of TIMP-1 in severe sepsis

The enzyme group of matrix metalloproteinases (MMPs) and their inhibitors, so-called tissue inhibitors of matrix-metalloproteinases (TIMPs), are crucial mediators responsible for wound repair after parenchymal damage. Little is known about the role of MMPs and TIMPs in severe sepsis. The aim of the present study was therefore to investigate their levels in patients with severe sepsis and to examine their association with prognosis. MMP-2, MMP-9, TIMP-1, TIMP-2 and interleukin-6 (IL-6) plasma levels were measured by ELISA methods in 37 patients on day 1 of severe sepsis. 37 healthy volunteers served as controls. Levels of MMP-9, TIMP-1, TIMP-2 and IL-6 in septic patients were significantly higher compared to healthy controls (p<0.001), whereas MMP-2 levels were not different in patients and controls. TIMP-1 levels were significantly higher in non-survivors (4675+/-435 ng/ml, mean+/-SEM) compared to survivors of severe sepsis (3201+/-249 ng/ml; p<0.01). Septic patients with TIMP-1 values >3200 ng/ml were 4.5 times more likely to die than patients with lower values (RR = 4.5; 95% CI 1.14-17.6, p = 0.014). Our results indicate that MMP-9, TIMP-2 and TIMP-1 are elevated in severe sepsis. Furthermore, TIMP-1 may serve as a useful laboratory marker to predict the clinical outcome of patients presenting with severe sepsis.     

Effect of polymyxin B-immobilized fiber on blood metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels in acute respiratory distress syndrome patients

BACKGROUND/AIMS: Metalloproteinase (MMP)-9 plays a role in the pathogenesis of acute respiratory distress syndrome (ARDS). Polymyxin B-immobilized fiber (PMX-F) treatment improves circulatory disturbance and oxygenation in ARDS patients. We aimed to assess whether PMX-F treatment alters the blood MMP-9 and tissue inhibitor of MMP (TIMP)-1 levels in ARDS patients. METHODS: Twelve ARDS patients who received PMX-F treatment and 20 healthy control volunteers were included in this study. PMX-F was carried out twice at a rate of 100 ml/min for 2 h with a time interval of 24 h. Blood MMP-9 and TIMP-1 levels were measured before and after PMX-F treatment. We monitored blood pressure and the PaO2/FiO2 (PF) ratio before and after PMX-F treatment. RESULTS: The mortality of ARDS patients after PMX-F treatment was 16.7%. Chest X-ray abnormalities were ameliorated in surviving patients after PMX-F treatment. Systolic and diastolic blood pressure increased significantly after PMX-F treatment (p < 0.01). The PF ratio also increased significantly after PMX-F treatment (p < 0.01). Blood MMP-9 and TIMP-1 levels in ARDS patients (126.4 +/- 36.4 and 326.5 +/- 52.5 ng/ml) were significantly higher than in controls (34.5 +/- 12.5 and 160.5 +/- 24.5 ng/ml; p < 0.01). PMX-F treatment reduced these levels significantly (the first treatment: MMP-9 85.4 +/- 28.6 ng/ml, p < 0.05, TIMP-1 265.8 +/- 36.6 ng/ml, p < 0.05; the second treatment: MMP-9 56.5 +/- 18.8 ng/ml, p < 0.01, TIMP-1 220.6 +/- 30.5 ng/ml, p < 0.01). CONCLUSION: These data suggest that MMP-9 and TIMP-1 may play a role in the pathogenesis of ARDS and that PMX-F treatment ameliorated increased MMP-9 and TIMP-1 levels in ARDS patients.