食管鳞癌中基质金属蛋白酶-7的表达及意义

目的:研究基质金属蛋白酶-7(MMP-7)在食管鳞癌中的表达情况及其与肿瘤浸润和淋巴结转移的关系。方法:用免疫组织化学法检测75例食管鳞癌组织及其相应正常粘膜中MMP-7的表达。结果:食管鳞癌组织MMP-7基因表达(59/75,78.7％)高于正常组织(P<0.01)。浸润到外膜层食管鳞癌(37/45,82.2％)与浸润至粘膜下层鳞癌(5/10,50.0％)之间MMP-7的高表达有显著性差异(P<0.05),淋巴结转移组MMP-7高表达(27/29,93.1％)高于淋巴结未转移组(P<0.05)。结论:MMP-7的高表达与食管鳞癌浸润深度和淋巴结转移有关,可能成为食管鳞癌恶性生物学行为的指标。     

基质金属蛋白酶9在大肠癌中表达的研究

目的 探讨基质金属蛋白酶9（MMP-9）在大肠癌中的表达及临床意义。方法 采用免疫组织化学SP法检测216例大肠癌组织中MMP-9的表达。结果 216例大肠癌组织MMP-9阳性表达率为76．9％（166／216），高表达率为65．3％（141／216）。MMP-9高表达与大肠癌的分化程度、Dukes分期、生存期、淋巴结转移和器官转移密切相关（P〈0．05或0．01）。结论 MMP-9高表达在大肠癌的侵袭和转移中发挥重要作用。     

眼睑基底细胞癌组织中基质金属蛋白酶-2和-9表达及其对预后判断的价值

眼睑基底细胞癌是眼睑恶性肿瘤中最常见的一种,常见于老年人,虽然发病缓慢,但其生物学行为仍有自身特点〔1〕。基质金属蛋白酶(MMP)-2和-9是MMPs家族重要成员,对细胞外基质(ECM)降解作用明显,对转移有明显促进作用〔2〕。本实验应用免疫组织化学技术检测眼睑基底细胞癌中MMP-2和-9表达,探讨二者在不同临床特征中的表达差别,关注二者相关性,以期为研究肿瘤生物学行为提供帮助。     

退行性变主动脉瓣基质金属蛋白酶-2及抑制剂-2的表达

摘要：目的 检测基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶抑制因子-2（TIMP-2）在退行性变主动脉三叶瓣的表达,探讨MMP-2、TIMP-2在退行性变主动脉三叶瓣中的作用与意义。方法 选取因主动脉瓣狭窄行手术切除的严重钙化的主动脉三叶瓣标本22例[男14例,女8例,年龄(66±6)岁]为研究组,因夹层动脉瘤行Bentall手术的正常三叶式主动脉瓣标本6例[男4例,女2例,年龄(43±5)岁]为对照组,病例来源为2015年-2018年天津胸科医院心外科住院患者;采用HE染色和免疫组织化学染色方法,观察退行性变主动脉瓣中MMP-2、TIMP-2的表达并对其进行分析。结果 MMP-2在正常主动脉三叶瓣中有低水平表达,在病变瓣膜有强烈表达,差异具有统计学意义;正常瓣膜与病变瓣膜TIMP-2的表达差异无统计学意义。结论 退行性变主动脉瓣中MMP-2表达水平增高,MMP-2可能参与退行性变主动脉瓣细胞外基质 (ECM)重构,导致主动脉瓣结构和功能障碍,在主动脉瓣退行性变的发生发展中起重要作用。     

组织蛋白酶B、基质金属蛋白酶-2在非小细胞肺癌中的表达及临床意义

目的探讨组织蛋白酶B(CB)和基质金属蛋白酶(MMP)-2在非小细胞肺癌发生、发展及转移中的作用。方法应用免疫组织化学法检测75例非小细胞肺癌组织及28例良性肺病变中CB和MMP-2的表达情况,并将检测结果与临床病理特征进行综合分析。结果 CB和MMP-2的表达主要定位于细胞质,CB和MMP-2在非小细胞肺癌中表达的阳性率明显高于良性肺病变(P0.05)。非小细胞肺癌中MMP-2蛋白的表达与有无淋巴结转移情况密切相关。肺癌组织中CB、MMP-2的表达水平呈显著正相关。结论 CB和MMP-2在非小细胞肺癌中表达上调,联合检测CB和MMP-2对肿瘤的诊断和预后判断有一定的临床意义。     

基质金属蛋白酶在食管癌组织中的表达及与微量元素含量之间的关系

目的:探讨MMP-9、MMP-2及微量元素在食管癌的发生、发展、浸润、转移过程中的作用及相互关系.方法:应用免疫组织化学(immunohistochemistry,IHC)SP法检测49例食管癌及16例癌旁组织中MMP-2、MMP-9蛋白的表达情况与食管癌的病理分型、分化程度、淋巴结转移及患者性别、年龄之间的相互关系.用AA-670原子吸收分光光度计测定食管癌组织中微量元素的含量.并对两者的结果做相关分析.结果:MMP-2、MMP-9蛋白的表达在食管癌中表达明显高于癌旁正常组织(69.3% vs 12.5%,71.4% vs 6.25%),且在有淋巴结转移组明显高于无淋巴结转移组(85.7% vs 47.6%,82.1% vs 52.3%),但在不同病理分型、年龄、性别、分期、分化程度中无明显统计学差异.食管癌组织中Zn含量及Zn/Cu显著低于癌旁正常食管组织Zn含量及Zn/Cu(8.13 μg/g±3.08 μg/g vs 11.63 μg±3.49 μg/g;7.50±3.65 vs 15.40±6.84),同时腺癌的Zn/Cu低于鳞癌的Zn/Cu(4.48±3.52 vs 8.02±3.45),食管腺癌组织中Se的含量显著高于食管鳞癌中Se的含量(0.91 μg/g±1.72 μg/g vs 0.29 μg±0.28 μg/g);有淋巴结转移组癌组织中Zn含量及Zn/Cu显著低于无淋巴结转移组癌组织中Zn含量及Zn/Cu(7.72 μg/g±3.03 μg/g vs 9.59 μg/g±3.06 μg/g;6.91±3.86 vs 9.93±4.81).而不同分化程度、不同分期、不同年龄、不同性别的食管癌中微量元素含量没有明显差别.结论:MMP-2、MMP-9及微量元素Zn的含量及Zn/Cu与在食管癌的发生发展及侵袭转移中可能起重要作用.联合检测微量元素、MMP-2与MMP-9有可能成为判断食管癌生物学行为的客观指标,对判断预后可能有一定价值.     

基质金属蛋白酶-2和-9在食管鳞状细胞癌中的过表达

目的 探讨人食管鳞癌组织中基质金属蛋白酶(MMP)-2、-9的表达及其临床意义.方法 采用免疫组织化学法,检测57例食管鳞癌及10例食管正常黏膜石蜡标本中MMP-2、-9蛋白的表达情况.结果 食管鳞癌组织中MMP-2及MMP-9阳性表达率(40.3%,61.4%)显著高于正常组织(0.0%,10.0%)(P＜0.05).食管鳞癌组织中MMP-2及MMP-9阳性表达与淋巴结转移和癌组织浸润深度有显著相关性(P＜0.05),而与患者的性别、年龄和组织分化程度无显著相关性(P＞0.05).结论 MMP-2和MMP-9在食管癌中显著高表达,与食管癌的转移及侵袭有关,其异常表达可能共同参与食管癌的发生、发展过程,检测MMP-2、-9可作为食管癌病理学特点的参考指标.     

基质金属蛋白酶-2及其抑制物在慢性肝炎和肝硬化肝组织中的表达

为进一步探讨基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-2组织抑制因子（TIMP-2）在肝纤维化发生，发展过程中的作用，用免疫组织化学方法检测慢性肝炎和肝硬化肝组织中MMP-2和TIMP-2的表达及分布状态，并作定位及半定量分析。     

基质金属蛋白酶及其抑制剂在老年人非小细胞肺癌中表达的研究

目的 研究基质金属蛋白酶MMP2、MMP9及组织基质金属蛋白酶抑制剂TIMPl、TIMP3在老年人非小细胞肺癌(NSCLC)中的表达及其与淋巴结转移的关系。方法 通过免疫组化方法检测103例老年人NSCLC组织中MMP2、MMP9、TIMPl、TIMP3表达情况．结果 MMP2、MMP9、TIMPl、TIMP3在老年人NSCLC组织表达阳性率分别为52．4％、62．1％、57．3％、52．4％。MMP2、MMP9与老年人NSCLC淋巴结转移呈正相关，而TIMPl、TIMP3与老年人NSCLC淋巴结转移成负相关．结论 MMP2、MMP9促进老年人NSCLC淋巴结转移。TIMPl、TIMP3抑制老年人NSCLC淋巴结转移，MMP2、MMP9、TIMPl、TIMP3可作为判断老年人NSCLC早期转移的指标。     

乳腺癌患者癌组织中组织蛋白酶D和基质金属蛋白酶-2的表达及其判断预后的价值

目的检测乳腺癌患者术后癌组织中组织蛋白酶D(Cath-D)和基质金属蛋白酶(MMP)-2表达及对预后判断的价值。方法应用免疫组织化学技术检测85例乳腺癌术后癌组织及40例乳腺组织Cath-D和MMP-2表达,探讨二者在不同临床特征中的表达意义。结果乳腺癌组织Cath-D和MMP-2阳性表达率明显高于正常乳腺组织,二者的表达与乳腺癌临床分期、淋巴结转移、肿瘤体积、雌激素受体(ER)、孕激素受体(PR)表达密切相关。乳腺癌组织中Cath-D和MMP-2的表达呈正相关性。生存分析显示Cath-D和MMP-2的表达与患者预后密切相关。结论乳腺癌组织Cath-D和MMP-2高表达,二者共同促进肿瘤发生发展,联合检测Cath-D和MMP-2表达水平可能预测患者预后。     

Interleukin-1 beta promotes matrix metalloproteinase expression and cell proliferation in calcific aortic valve stenosis

Calcific aortic valve stenosis (AS), the main heart valve disease in the elderly, is characterized by extensive remodeling of the extracellular matrix. Matrix metalloproteinases (MMPs) are upregulated in calcific AS and might modulate matrix remodeling. The regulatory mechanisms are unclear. As recent studies have suggested that calcific AS might result from an inflammatory process involving leukocyte invasion and activation, the present study aimed to elucidate the role of the pro-inflammatory cytokine interleukin (IL)-1β on MMP expression and cell proliferation in human aortic valves. Immunohistochemistry for leukocytes, IL-1β and MMP-1 was performed on aortic valves with (n=6) and without (n=6) calcification obtained at valve replacement or autopsy. Stenotic valves showed marked leukocyte infiltration and associated expression of IL-1β and MMP-1. In control valves only scattered leukocytes, low staining for MMP-1 and no staining for IL-1β were present. Double-label immunostaining localized IL-1β expression mainly to leukocytes and MMP-1 expression to myofibroblasts. Stimulation of cultured human aortic valve myofibroblasts with IL-1β lead to a time-dependently increased expression of MMP-1 and MMP-2 by Western blotting and zymography, whereas MMP-9 remained unchanged. Cell proliferation was increased by IL-1β as determined by bromodesoxyuridine incorporation. Thus, IL-1β may regulate remodeling of the extracellular matrix in calcific AS.     

基于超声心动图的钙化性主动脉瓣疾病患病情况的回顾性研究

目的分析钙化性主动脉瓣疾病(CAVD)的患病情况。方法收集并回顾性分析行超声心动图检查年龄≥45岁患者的临床资料17 826例,男性9725例,女性8101例,其中45⁶4岁11 274例,6564岁11 274例,65⁷4岁4250例,7574岁4250例,75⁸4岁2052例,≥85岁250例。结果CAVD总患病率为12.8%,男性CAVD患病率明显高于女性(13.6%vs11.9%),CAVD发生年龄明显低于女性[(70±10)岁vs(71±10)岁,P=0.001]。CAVD患病率随着年龄增长明显增高,4584岁2052例,≥85岁250例。结果CAVD总患病率为12.8%,男性CAVD患病率明显高于女性(13.6%vs11.9%),CAVD发生年龄明显低于女性[(70±10)岁vs(71±10)岁,P=0.001]。CAVD患病率随着年龄增长明显增高,45⁶4岁,6564岁,65⁷4岁,7574岁,75⁸4岁,≥85岁4个年龄段患病率分别为5.3%、20.5%、32.9%和54.4%。CAVD患者最常受累及的瓣叶为无冠瓣,其次是右冠瓣+无冠瓣、右冠瓣和左冠瓣。CAVD患者常见的功能异常为主动脉瓣反流,且主动脉瓣反流较狭窄明显多见(77.1%vs 15.0%,P<0.01)。CAVD患者左心房扩大发生率明显高于左心室扩大(56.3%vs 22.2%),室间隔肥厚发生率明显高于左心室后壁(51.7%vs 24.2%,P<0.01)。结论 CAVD患病率随年龄增长显著增高。     

重视老年钙化性主动脉瓣狭窄的防治研究

钙化性主动脉瓣狭窄(CAVS)是老年人的多发病,由于其无症状期漫长,先前一直被认为是"良性的"被动性老年退变现象。新近研究发现,CAVS的病变实际上是主动的发展过程,最终并可导致严重后果。到后期,一旦出现症状,病情很快恶化,致死率很高,此时只能进行外科换瓣手术解除狭窄,抢救和延长生命。目前尚无其他有效办法防止CAVS的发生、发展,亟待深入研究。     

Aortic valve annulus diameter in Chinese patients with severe calcific aortic valve stenosis: implications for transcatheter aortic valve implantation

Objectives : The objective of the study was to describe the distribution and determine the predictors of aortic valve annulus diameter (AVAD) in Chinese patients with severe calcific aortic valve stenosis (CAS). Background : AVAD in Chinese patients with CAS has not been reported. Predictors of AVAD in patients with CAS are unclear. Methods : One hundred elderly patients (≥60 years) with severe CAS were included in the study. AVAD in all patients was measured by transthoracic echocardiograph (AVAD‐TTE) and in 74 patients of them was measured intra‐operatively (AVAD‐intra). Results : The intraclass correlation coefficient (ICC) between AVAD‐TTE and AVAD‐intra was 0.81 (95% CI: 0.72–0.88). The differences between AVAD‐TTE and AVAD‐intra ranged from ?3 to 3 mm and were ≤≤ 2mm in 91.9% (68/74) of patients. The intra‐observer ICC for TTE was 0.87 (95% CI: 0.74–0.94). Mean AVAD in the whole population was 21.80 ± 2.09 (17–27) mm. 11% of cases had an AVAD < 20 mm, 78% had an AVAD between 20 and 24 mm, and 11% had an AVAD between 25 and 27 mm. The correlation between AVAD and height (r = 0.476, P < 0.001) was stronger than that between AVAD and weight (r = 0.215, P = 0.034) or body surface area (BSA) (r = 0.358, P < 0.001). Multivariate regression showed that height, sex, and age but not BSA were independent predictors of AVAD (all P < 0.05). Conclusion : Most of Chinese patients with CAS can be candidates for transcatheter aortic valve implantation procedure in terms of AVAD, whereas more sizes of prosthetic valves need to be developed. Sex, age, and especially height, but not BAS, are independent predictors of AVAD in patients with CAS. © 2011 Wiley Periodicals, Inc.     

The vitamin D receptor genotype predisposes to the development of calcific aortic valve stenosis

OBJECTIVE—To test the hypothesis that vitamin D receptor polymorphism is associated with calcific aortic valve stenosis.
DESIGN—The distribution of one polymorphism of the vitamin D receptor (BsmI B/b) was examined in 100 consecutive patients with calcific valvar aortic stenosis and compared with a control group of 100 patients (paired match for age, sex, and the presence of coronary artery disease from a total of 630 patients without calcified aortic valves). Polymerase chain reaction and restriction fragment length polymorphism were used to determine genotypes.
RESULTS—There was a significant difference in vitamin D receptor allele and genotype frequencies between the two groups. The allele B had a higher prevalence in patients with calcific aortic stenosis (B = 0.56, b = 0.44) than in the control cohort (B = 0.40, b = 0.60) (p = 0.001).
CONCLUSIONS—There is a significant association of vitamin D receptor polymorphism with calcific aortic valve stenosis. The B allele of the vitamin D receptor is more common in patients with calcific aortic valve stenosis. It now needs to be evaluated whether other genes that control calcium homeostasis are involved in the pathogenesis of this disorder.


Keywords: vitamin D receptor; calcific aortic stenosis; aortic valve; genetic polymorphism     

The impact of mitral stenosis on outcomes of aortic valve stenosis patient undergoing surgical aortic valve replacement or transcatheter aortic valve replacement

Background

The concomitant presence of mitral stenosis (MS) in the setting of symptomatic aortic stenosis represent a clinical challenge. Little is known regarding the outcome of mitral stenosis (MS) patients undergoing transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). Therefore, we sought to study the outcome of MS patients undergoing aortic valve replacement (AVR).

Method

Using weighted data from the National Inpatient Sample (NIS) database between 2011 and 2014, we identified patients who were diagnosed with MS. Patients who had undergone TAVR as a primary procedure were identified and compared to patients who had SAVR. Univariate and multivariate logistic regression analysis were performed for the outcomes of in‐hospital mortality, length of stay (LOS), blood transfusion, postprocedural hemorrhage, vascular, cardiac and respiratory complications, permanent pacemaker placement (PPM), postprocedural stroke, acute kidney injury (AKI), and discharge to an outside facility.

Results

A total of 4524 patients were diagnosed with MS, of which 552 (12.2%) had TAVR and 3972 (87.8%) had SAVR. TAVR patients were older (79.9 vs 70.0) with more females (67.4% vs 60.0%) and African American patients (7.7% vs 7.1%) (P < 0.001). In addition, the TAVR group had more comorbidities compared to SAVR in term of coronary artery disease (CAD), congestive heart failure (CHF), chronic lung disease, hypertension (HTN), chronic kidney disease (CKD), and peripheral vascular disease (PVD) (P < 0.001 for all). Using Multivariate logistic regression, and after adjusting for potential risk factors, TAVR patients had lower in‐hospital mortality (7.9% vs 8.1% adjusted Odds Ratio [aOR], 0.615; 95% confidence interval [CI], 0.392–0.964, P = 0.034), shorter LOS. Also, TAVR patients had lower rates of cardiac and respiratory complications, PPM, AKI, and discharge to an outside facility compared with the SAVR group.

Conclusion

In patients with severe aortic stenosis and concomitant mitral stenosis, TAVR is a safe and attractive option for patients undergoing AVR with less complications compared with SAVR.

     

先天性免疫在钙化性主动脉瓣疾病中的作用

钙化性主动脉瓣疾病(CAVD)是影响心脏瓣膜的最常见疾病,其特征是主动脉瓣瓣小叶的增厚、纤维化和矿化,目前尚无有效的药物治疗。主动脉瓣钙化是一个复杂的、多因素影响的过程,包括瓣膜炎症、纤维化、钙化以及瓣膜增厚和心流出道阻塞。CAVD的确切病理生理机制尚不完全清楚,但许多研究表明先天免疫细胞在主动脉瓣钙化的发展中起关键作用。该综述主要阐述目前关于先天性免疫细胞在CAVD发展中的作用。     

Successful transfemoral aortic valve replacement in a bicuspid aortic stenotic valve: Requirements for a safe implant

Although transcatheter aortic valve replacement (TAVR) has been accepted as an attractive alternative for high‐risk patients with severe symptomatic aortic stenosis (AS), patients with congenital bicuspid AS has been typically disqualified for this indication due to an implied risk of device dislocation, distortion, or device malfunctioning. Nonetheless, bicuspid AS is not uncommon and frequently missed by transthoracic echocardiography. We reported an interesting case of a high‐risk patient with severe symptomatic bicuspid AS who underwent successful TAVR and discussed the anatomic requirements for a safe implant in patients with bicuspid AS considered candidates for TAVR. © 2013 Wiley Periodicals, Inc.     

基质金属蛋白酶-2、-9与肝纤维化

研究基质金属蛋白酶－2（MMP－2）、基质金属蛋白酶－9（MMP－9）在实验性肝纤维化发生发展过程中的表达及动态变化。用皮下注射CCL4的方法复制大鼠化学性肝纤维化模型。用免疫组织化学方法在4周、8周、12周分别检测肝组织中MMP－2、MMP－9的表达。MMP－2主要位于血管内皮细胞、窦内皮细胞及肝窦细胞的胞浆；MMP－9主要位于静 肝细胞及肝窦细胞的胞浆。MMP－2、MMP－9免疫组化阳性表达面积，肝纤维化明显高于对照组（P＜0．05），并随造模时间延长而进行性增加。MMP－2、MMP－9参与了肝纤维化的进展，可能促进作用。