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1.
目的 探讨经颈静脉肝内门腔分流术(TIPS)后再狭窄多种组织成分的变化,为揭示TIPS分流道再狭窄的形成机制提供更多的信息。方法 对6只25kg左右的家猪进行TIPS术,建成TIPS猪模型。14~21d后处死,取出肝脏TIPS组织做病理检查,包括大体标本检查,电镜检查,病理切片分别用HE染色、免疫组化分析anti-SMC-α抗平滑肌肌动蛋白-α)、细胞增殖核抗原(PCNA)、波形蛋白(vimentin)、肌球蛋白(mvoglobulin)、eNOS(内皮型一氧化氮合酶)及iNOS(诱导型一氧化氮合酶)等多个指标表达。将TIPS再狭窄组织与通畅的支架通道组织进行上述多项指标的对比分析。结果 TIPS术后2~3周处死时,6只猪有4只猪出现不同程度再狭窄,其中有2只TIPS通道完全堵塞。电镜检查,再狭窄组织含大量增殖的胶原纤维、大量平滑肌细胞与成纤维细胞;抗SMC-α、PCNA在再狭窄组织中表达为强阳性,在TIPS通道通畅的组织中,也有较强表达;波形蛋白在通畅的支架通道组织中表达为强阳性,而在支架再狭窄组织中表达明显减弱;肌球蛋白正好相反,在再狭窄组织中表达较强,而在通畅的支架组织中表达减弱;eNOS在正常肝脏组织中为阳性表达,靠近TIPS再狭窄组织,表达有减弱;而iNOS在正常肝脏组织中为表达弱阳性,但靠近TIPS再狭窄组织,表达明显增强。结论 猪TIPS模型中,再狭窄中主要为抗SMC-α阳性的平滑肌细胞增殖,细胞增殖迁移能力强;正常肝脏组织中主要表达eNOS,而肝脏损伤后iNOS表达明显增强。  相似文献   

2.
肌成纤维细胞在皮肤瘢痕形成过程中的作用   总被引:2,自引:0,他引:2  
目的 探讨表达α平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)的肌成纤维细胞在皮肤增牛性瘢痕中的作用.方法 免疫组织化学法检测皮肤增牛性瘢痕中α-SMA的表达;通过细胞培养,检测成纤维细胞与肌成纤维细胞羟脯氨酸含量并进行比较;ELISA法分别检测成纤维细胞与肌成纤维细胞Ⅲ型前胶原、纤维连接蛋白、TGF-β1含量并进行比较.结果 正常皮肤组织只有血管平滑肌细胞表达α-SMA,其他真皮细胞几乎不表达,增生性瘢痕皮肤组织中,α-SMA染色阳性细胞大大增加,比例高达96.89%,两者比较,差异有统计学意义(P<0.01);肌成纤维细胞羟脯氨酸含量较正常成纤维细胞显著增高(P<0.01);肌成纤维细胞Ⅲ型前胶原含量较成纤维细胞显著增高(P<0.05);肌成纤维细胞TGF-β1含量较正常成纤维细胞显著增高(P<0.01);肌成纤维细胞纤维连接蛋白含量较成纤维细胞显著增高(P<0.05).结论 肌成纤维细胞是造成增生性瘢痕的最关键细胞.  相似文献   

3.
目的 评价内皮祖细胞(EPC)种植支架在经颈静脉肝内门腔分流(TIPS)家猪动物模型中减少分流道再狭窄的疗效.方法 体外分离、培养、鉴定家猪外周血内皮祖细胞,并构建内皮祖细胞种植支架.15头家猪行TIPS介入手术,采用随机区组设计分为EPC种植支架组9头(实验组),裸支架组6头(对照组).术后14 d行直接门静脉造影,然后处死动物,作病理分析及免疫组织化学检查,记录分流道狭窄及阻塞率,并用图像处理软件计算TIPS分流道假性内膜厚度及面积.计数资料用Fisher精确概率法,计量资料行t检验,作统计学分析.结果 15头猪TIPS手术均成功.实验组分流道通畅5头,狭窄2头(狭窄率50%、70%),阻塞2头(共9头).对照组狭窄1头(狭窄率80%),阻塞5头(共6头).2组通畅率差异有统计学意义(P=0.03).实验组假性内膜增生的厚度(肝静脉、肝实质、门静脉段)显著小于对照组[分别为(1.0 ±0.6)、(0.9±0.5)、(1.0±0.4)mm和(1.2±0.4)、(1.3±0.5)、(1.5±0.4)mm,P值均<0.05].免疫组织化学显示实验组中通畅的分流道有完整的内皮形成;再狭窄分流道的假性内膜主要由胶原纤维组成,而通畅分流道的假性内膜主要由细胞成分组成.结论 体外构建EPC种植支架是可行的,置入后促进了家猪模型TIPS分流道内皮化形成,可以提高分流道的通畅性.  相似文献   

4.
覆膜支架防治TIPS分流道再狭窄的研究进展   总被引:3,自引:1,他引:2  
覆膜支架已被越来越多地应用于经颈内静脉肝内门腔静脉分流术(TIPS)分流道再狭窄的防治中,取得了较大进展,Viatorr支架已被证明可以更好地改善分流道通畅率。本文就各种TIPS覆膜支架的结构、性质、应用及疗效等作一综述,相信随着覆膜支架的不断改善,TIPS在治疗门脉高压疾病领域中将重新盛行。  相似文献   

5.
目的探讨鞘鞍醇激酶-2(SPHK2)在转化生长因子-β1(TGF-β1)诱导心脏成纤维细胞增殖与活化中的作用。方法分离乳鼠心脏成纤维细胞并体外培养。利用慢病毒分别将对照或SPHK2小分子干扰RNA(siRNA)转染心脏成纤维细胞。采用Western blot检测siRNA对SPHK2蛋白的干扰效率;采用酶联免疫吸附法检测心脏成纤维细胞1-磷酸鞘鞍醇(S1P)水平;采用TGF-β1处理诱导对照组和SPHK2 siRNA组心脏成纤维细胞增殖与活化后,CCK8法检测心脏成纤维细胞增殖能力,Western blot检测心脏成纤维细胞活化的标记蛋白α-平滑肌激动蛋白(α-SMA)的表达,q-PCR检测心脏成纤维细胞胶原蛋白Ⅰ(ColⅠ)和胶原蛋白Ⅲ(ColⅢ)的mRNA水平。结果慢病毒转染SPHK2 siRNA后,心脏成纤维细胞SPHK2蛋白表达水平显著低于对照组,组间比较,差异有统计学意义(P<0.05)。SPHK2 siRNA组心脏成纤维细胞S1P水平显著低于对照组,组间比较,差异有统计学意义(P<0.05)。给予TGF-β1处理后,SPHK2 siRNA组心脏成纤维细胞增殖能力、α-SMA蛋白和mRNA表达、ColⅠ和ColⅢ的mRNA表达显著低于对照组,组间比较,差异有统计学意义(P<0.05)。结论下调SPHK2表达可抑制TGF-β1诱导心脏成纤维细胞的增殖与活化。  相似文献   

6.
目的 观察腱鞘成纤维细胞经反义TGF-β1基因修饰后生物学活性的改变,为肌腱术后粘连防治提供新的思路.方法 取新西兰白兔6只,分离、培养腱鞘成纤维细胞,利用脂质体将反义TGF-β1表达载体pcDNA3-TGF-β(-)导入腱鞘成纤维细胞,RT-PCR检测肌腱细胞TGF-β1、Ⅰ、Ⅲ型胶原mRNA的表达,Western blot法检测Ⅰ型胶原蛋白的表达.结果 RT-PCR显示基因修饰后肌腱细胞TGF-β1、Ⅰ、Ⅲ型胶原的mRNA表达显著降低,与未传染组和空转染组比较,差异有统计学意义(P<0.01);Western blot结果 显示基因修饰后肌腱细胞Ⅰ型胶原蛋白表达降低,与未传染组和空转染组比较,差异有统计学意义(P<0.01). 结论 反义TGF-β1质粒能成功导入肌腱细胞中,并有效降低TGF-β1的表达和Ⅰ、Ⅲ型胶原的产生,减少肌腱的粘连成分,可能为防止肌腱损伤后的粘连起一定的作用.  相似文献   

7.
脾静脉狭窄可用血管内支架来治疗。作者报道1例酒精性肝硬化引起上消化道出血的病例,保守治疗无效后行TIPS治疗。门静脉造影显示有严重的胃静脉曲张及脾静脉5cm长的狭窄段。在用一个Wallstent作了肝内分流后,测得该门脉压力虽降低,脾静脉狭窄段两端仍有17mmHg的压力差,胃静脉曲张未消失,即用第二个Wallstent放入脾静脉狭窄段。结果胃静脉曲张消失,脾静脉狭窄两端无压力差,病人出血被控制。以后反复US检查均见肝内分流通畅,脾静脉无再狭窄。脾静脉狭窄为酒精性肝病合并酒精性胰腺炎的一种不少见并发症。这种病人  相似文献   

8.
目的 探讨RNA干扰阻滞胸腺素β1表达对TGF-β1诱导人肾小管上皮-肌成纤维细胞转分化(EMT)的抑制作用.方法 构建能表达针对胸腺素β1的小干扰RNA(siRNA)的重组腺病毒载体,以及表达不针对任何已知mRNA的siRNA的阴性对照载体,分别感染人肾小管上皮细胞株(HKC),得到胸腺素β1表达受抑制的HKC-siTβ4和胸腺素β4表达未受影响的HKC-siC.根据用TGF-β1处理HKC、HKC-siTβ4和HKC-siC的情况,将培养的细胞分为4组:正常HKC组(C组),TGF-β1处理HKC组(T C组),TGF-β1处理HKC-siTβ1组(T siTβ1组)和TGF-β1处理HKC-sic组(T siC组).48h后,分别采用RT-PCR和Western blotting检测各组胸腺素β1、α-平滑肌肌动蛋白(α-SMA)和E-钙黏素表达,并分析胸腺素β1和α-SMA表达量的相关性.结果 C组胸腺素β4表达弱阳性,α-SMA表达阴性,E-钙黏素表达强阳性;T C组胸腺素β1和α-SMA表达强阳性,E_钙黏素表达较C组减弱(P<0.01);T siTβ1组胸腺素β1和α-SMA表达弱阳性,表达量显著低于T C组(P<0.01),E-钙黏素显著高于T C组(P<0.01);T siC组胸腺素β1、α-SMA和E-钙黏素表达与T C组相比均无显著差异(P>0.05).胸腺素β4和α-SMA表达呈显著正相关.结论 RNAi阻滞胸腺素β4表达能有效地抑制TGF-β1诱导EMT,提示胸腺素β4是介导TGF-β1诱导EMT的重要分子.  相似文献   

9.
目的 观察放射性肺损伤过程中基质金属蛋白酶12(MMP-12)过表达对肺成纤维细胞转化的作用.方法 32只雄性Wistar大鼠,体重250~280g,随机分为正常对照组(n=8)和照射组(n=24).照射组用20Gy60Co γ射线进行全胸照射,分别于照射后1、2、4周行肺组织取材,每时间点8只.应用明胶酶谱法检测MMP-12酶活性变化,组织特殊染色法观察肺泡壁弹力纤维降解情况,透射电镜观察肺泡Ⅱ型上皮细胞与肺间质细胞间的"信号交流"(cross talking)现象,ELISA法检测肺组织中TGF-β1含量,免疫组化检测肺组织a-平滑肌肌动蛋白(a-SMA)表达情况.结果 MMP-12酶活性在照射后1周开始增高,至照射后4周时有所下降;肺泡壁基底膜弹力纤维照射后1周开始出现降解断裂,4周时最为严重;肺组织TGF-β1含量和a-SMA免疫组化阳性信号在1~4周内随照后时间延长而逐渐升高.电镜观察肺泡Ⅱ型上皮细胞与肺间质细胞间出现"信号交流"现象.结论 照射后肺组织MMP-12酶活性增高,可能通过降解基底膜弹力纤维促进成纤维细胞转化,启动肺纤维化的发生.  相似文献   

10.
目的 探讨放射性肺损伤过程中吡啡尼酮对抗肺成纤维细胞(Fb)向肌成纤维细胞(MFb)转化的作用。方法 将Wistar大鼠随机分为正常对照组、单纯照射组和照射+给药组,照射前2 d开始灌胃给予吡啡尼酮,用20 Gy60Co γ射线进行全胸照射,于照射后2周应用图像分析测定肺组织放射性炎性反应范围的面密度;计算肺组织湿/干重比;免疫组化检测肺组织成纤维细胞α-平滑肌肌动蛋白(α-SMA)表达。应用免疫细胞化学和四甲基偶氮唑盐(MTT)比色法分别检测人肺成纤维细胞(HLF)表达TGF-β1和细胞异常增生的程度。结果 和单纯照射组相比,照射+给药组大鼠肺组织炎性病变区面密度、湿/干重比和α-SMA含量较照射组分别减少14.0%、3.82%和 52.8%。吡啡尼酮可抑制照射促进HLF表达TGF-β1和细胞增生的作用,且此种抑制作用和给药剂量呈明显的依赖关系。 结论 吡啡尼酮对放射性肺损伤早期的间质性肺炎具有明显的对抗作用,并且可显著抑制肺Fb异常增生、TGF-β1表达和向肌成纤维细胞方向转化,有利于放射性肺纤维化的有效防治。  相似文献   

11.
PURPOSE: To investigate the feasibility, safety, and efficacy of an autologous vein-covered stent (AVCS) to prevent shunt stenosis in a porcine transjugular intrahepatic portosystemic shunt (TIPS) model. MATERIALS AND METHODS: TIPS were created with an AVCS in 12 healthy domestic swine and with a bare stent in 10 additional swine. Tissue response was compared with use of venography, histology, and computerized morphometry analysis 2 weeks after implantation. Differences between AVCS and noncovered stents (established by a t-test), as well as regional differences within a single stent (established by an f test), were considered significant at P <.05. RESULTS: Twenty of 22 TIPS procedures were technically successful. Ten of 12 shunts with an AVCS (83%) and two of 10 with bare stents (20%) remained patent (<50% diameter narrowing) at euthanasia 2 weeks later (P <.01). Histologic evaluation of harvested bare stents showed marked intimal hyperplasia (IH), composed of smooth muscle cells, myofibroblasts, and fibroblasts. In contrast, the AVCS were remarkably free of IH and thromboses. In patent TIPS in both groups, endothelial coverage of the luminal surface was present histologically. IH accounted for 57% (26.27/45.79) of total stent cross-sectional lumen area in the control group and 21% (8.34/39.54) in the AVCS group (P <.01), with no intrashunt differences (P >.05). CONCLUSION: Based on short-term follow-up, AVCS significantly improved TIPS patency by prevention of both IH and in-stent thrombosis. TIPS created with an AVCS was feasible and safe in our porcine model.  相似文献   

12.

Objective

We wanted to evaluate the feasibility and efficacy of using a dexamethasone (DM)-eluting nitinol stent to inhibit the pseudointimal hyperplasia following stent placement in the transjugular intrahepatic portosystemic shunt tract (TIPS) of a swine.

Materials and Methods

Fifteen stents were constructed using 0.15 mm-thick nitinol wire; they were 60 mm in length and 10 mm in diameter. The metallic stents were then classified into three types; type 1 and 2 was coated with the mixture of 12% and 20%, respectively, of DM solution and polyurethane (PU), while type 3 was a bare stent that was used for control study. In fifteen swine, each type of stent was implanted in the TIPS tract of 5 swine, and each animal was sacrificed 2 weeks after TIPS creation. The proliferation of the pseudointima was evaluated both on follow-up portogram and pathologic examination.

Results

One TIPS case, using the type 1 stent, and two TIPS cases, using the type 2 stent, maintained their luminal patency while the others were all occluded. On the histopathologic analysis, the mean of the maximum pseudointimal hyperplasia was expressed as the percentage of the stent radius that was patent, and these values were 51.2%, 50% and 76% for the type 1, 2, and 3 stents, respectively.

Conclusion

The DM-eluting stent showed a tendency to reduce the development of pseudointimal hyperplasia in the TIPS tract of a swine model with induced-portal hypertension.  相似文献   

13.
As part of a series of basic experiments on using metallic stents for treatment of vascular stenosis, a chronological examination of changes in dog aorta following implantation of a self-expandable metallic stent was conducting using transmission and scanning electron microscopy. The Giantruco stent was placed in the abdominal aorta via the right carotid artery. One week after insertion, the aortic intima was depressed and degenerative changes observed in both endothelial and medial smooth muscle cells. After 2 weeks, except for the bend portion, the stent was covered with neointima. The neointimal surface was covered by premature endothelial cells with abundant microvilli and prominent nuclear protrusions. Under the endothelial cells, immature mesenchymal cells, such as fibroblast, were scattered throughout the edematous intercellular space. At 4 weeks, the stent was completely covered by neointima and the endothelial cells had flattened and few microvilli were in evidence. In this thickened intima, premature smooth muscle cells with myofilaments and basement membranes were observed but, around them, few collagen fibers and only occasional elastic fibers were found. At 6 weeks, the intimal surfaces were flat and smooth with a slight intimal elevation over the stent. No thrombus was observed throughout the period of the experiment. The above results indicate that dilation using metallic stents may be a useful method for treatment of vascular stenosis.  相似文献   

14.
经颈静脉肝内门体静脉内支架分流术术式改良的实验研究   总被引:7,自引:1,他引:6  
目的:探讨建立改良式猪经颈静脉肝内门体静脉内支架分流术(TIPSS)模型的可行性及其意义。方法:11只家猪分成2组,7只采用改良术式(经肝段下腔静脉穿刺门脉)建立TIPSS模型,另4只行常规TIPSS作对照。共置入4枚进口覆膜镍钛合金支架,8枚国产覆聚氨酯膜支架。其中,改良组7只猪置入7枚支架(4枚进口支架,3枚国产支架);对照组4只猪置入5枚国产覆膜支架(1只猪置入时支架发生移位,故加用1枚支架)。术后4周(5只),8周(2只)和12周(4只)进行门脉造影观察分流道通畅情况。动物处死后,行分流道大体和组织病理学检查。结果:术后4周,改良组2只分流道通畅(进口支架、国产支架各1枚),分流道表面均形成完整的假性内膜组织;另5只分流道在4至12周均闭塞,分流道内形成血栓,其中2只内支架伸入下腔静脉内不全,陷入肝实质内。常规组4只分流道在4、8和12周观察期内均闭塞。两组间分流道肝(下腔)静脉端,肝实质段和门静脉端各段的增生组织厚度对比差异均无显著性意义(t值分别为0.14、0.16和0.20,P值均>0.05)。结论:改良式猪TIPSS模型的建立是安全和可行的。改良式TIPSS中应采用覆膜支架,并应有足够长度伸入至两端静脉内,有助于防止增生组织向分流道内长入。  相似文献   

15.
A percutaneous transjugular intrahepatic portocaval shunt (TIPS) was successfully performed using Wallstents in a 53-year-old man with neoplastic disease causing portal hypertension and life-threatening variceal hemorrhage. Shortly after-wards, recurrent hemorrhage was investigated by shunt venography which showed that extrinsic narrowing of the hepatic vein and hepatic vena cava was causing shunt thrombosis. Shunt thrombosis was cleared by balloon occlusion of the shunt and forceful retrograde flushing of thrombus into the portal circulation. The compressed hepatic vein and vena cava were then dilated and stented using Gianturco “Z” stents. Bleeding recurred 3 months later due to focal narrowing within the shunt which possibly was due to intimal proliferation. Repeat dilatation and placement of a coaxial Palmaz stent again relieved portal hypertension. Creation of a TIPS for portal hypertension secondary to neoplasm can produce valuable palliation. Complete assessment of hepatic vein and vena cava patency is required to ensure shunt function.  相似文献   

16.
Haskal ZJ  Brennecke LH 《Radiology》1999,213(3):853-859
PURPOSE: To evaluate the safety, efficacy, and tissue response associated with Wallstents covered with polyethylene terephthalate (PETP) compared with those associated with uncovered Wallstents for creation of transjugular intrahepatic portosystemic shunts (TIPS) in a porcine model. MATERIALS AND METHODS: Thirteen TIPS were created in 13 minipigs: eight with PETP-covered Wallstents, five with standard Wallstents. Shunt venography was performed at 5-8 weeks, and necropsy was performed at 7-8 weeks. Histopathologic, immunohistochemical, and scanning electron microscopic examinations were performed. RESULTS: Mean shunt stenoses of the control and graft groups were 45% and 53%, respectively. Graft stenoses involved the entire graft-bearing segment, whereas bare stent stenoses were localized within the liver tract. Myofibroblast and extracellular collagen matrix proliferation encompassed both control and graft-covered stents. There was one graft TIPS occlusion. One control TIPS stenosis was due to transstent proliferation of normal porcine hepatic tissue. A small focus of bile staining was seen on the abluminal surface of one TIPS, which was a patent PETP-lined shunt. CONCLUSION: PETP graft TIPS provided equal, but not superior, patency to that of bare stent TIPS. The pattern of PETP TIPS graft healing differed from that of bare stents but was similar to that reported with other polyester graft vascular implants and consisted of diffuse transmural penetration and paving of the graft surface by extracellular collagen matrix and myofibroblasts.  相似文献   

17.
Purpose To assess the suitability of spiral Z-stents for transjugular intrahepatic portosystemic shunt (TIPS) and the influence of portal hypertension on shunt patency in young swine. Methods TIPS were established using spiral Z-stents in 14 domestic swine. In 7 animals, the portal venous pressure was normal; in the other 7, acute portal hypertension was induced by embolization of portal vein branches. Follow-up portal venography and histologic evaluations were done from 1 hr to 12 weeks after TIPS. Results Follow-up transhepatic portal venograms showed progressive narrowing of the shunt, most priminent in the midportion of the tract. Ingrowth of liver parenchyma between the stent wires found after 3 weeks led to progressive shunt narrowing and shunt occlusion by 12 weeks. A pseudointima grew rapidly inside the stent, peaked in thickness around 4 weeks, and decreased later. Acutely created portal hypertension rapidly returned to normal and there was no difference in TIPS patency between the two groups of animals. Conclusion Although the spiral Z-stent can be used as a device for creation of TIPS in patients with cirrhotic livers, it is associated with extensive liver ingrowth in swine that leads to rapid shunt occlusion. Portal hypertension was only transient in this model.  相似文献   

18.
Purpose: To assess the histologic findings associated with stenosed and occluded transjugular intrahepatic portosystemic shunt (TIPS) tracts. Methods: Four TIPS tracts within three autopsy livers were histologically studied for vascular components by routine staining and immunohistochemical staining. TIPS had been performed for bleeding from esophageal varices in patients with cirrhosis of the liver. Results: Two TIPS, examined on days 4 and 53, showed occlusion by fibrin thrombus. In the former, no endothelial cells were detected, but coagulative necrosis of hepatocytes was found in the surrounding liver. In the latter, bile pigments were seen on the luminal surface. In the two other TIPS without tract occlusion, examined on days 49 and 293, a layer of endothelial cells, proliferation of smooth muscle cells, and deposition of an extracellular matrix such as collagen were confirmed. In the tract examined on day 293, there was protrusion of hepatocytes into the lumen through the stent wires. Conclusion: Short- and midterm TIPS occlusions were caused by thrombus forming after necrosis of hepatocytes and bile leakage, respectively. Long-term TIPS stenosis was associated with a combination of pseudointimal hyperplasia and ingrowth of hepatocytes. Received: 0/00/00/Accepted: 0/00/00  相似文献   

19.
The aim of this study was to investigate the efficacy and feasibility of local delivery of paclitaxel to inhibit pseudointimal hyperplasia/intimal hyperplasia in swine transjugular intrahepatic portosystemic shunt (TIPS) models TIPS were created in seven healthy domestic swine (15-20 kg). Before TIPS stent insertion, we performed a short-term infusion of paclitaxel (treatment group: n = 4) and saline (control group: n = 3) into the TIPS tract using a balloon catheter in which two 0.010 inch holes were created on opposite sides of the balloon. Paclitaxel or saline was given to all animals via the hepatic parenchymal and venous outflow tract. The animals were followed for up to two weeks and then killed. Gross and histological evaluations of the shunts were performed, and the maximum pseudointimal/intimal hyperplasia thicknesses were calculated for each animal The average infusion time of paclitaxel or saline was 7.6 min (6-9 min). At gross and histological evaluation, considerable pseudointimal hyperplasia had formed in the control group and statistically significant differences were found upon microscopic evaluation in the maximum pseudointimal hyperplasia thickness between the control (2.41 mm, range 1.7-3.16 mm) and animals receiving paclitaxel (0.63 mm, range 0.42-0.98 mm, p<0.05) Local delivery of paclitaxel at the time of TIPS creation may have been effective in reducing pseudointimal/intimal hyperplasia in swine TIPS models.  相似文献   

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