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1.
目的研究雷奈酸锶治疗人工关节磨损微粒诱导骨溶解的作用,探讨防治人工关节置换术后假体松动的可能性。方法采用小鼠建立Co—Cr-Mo微粒诱导骨溶解的颅骨模型,分为4组:A组为空白组,B组为颗粒对照组,C组为低剂量治疗组,D组为高剂量治疗组。28d后取出颅骨进行HE染色观察颅骨骨溶解面积,通过EUSA方法检测TNF—α和RANKL的表达,qRT-PCR方法检测RANKL和OPG的表达并分析RANKL/OPG比率变化。结果雷奈酸锶可以明显抑制微粒诱导的骨溶解,对下调TNF-α和RANKL蛋白有确切的疗效,而且这种改变与雷奈酸锶的剂量有关。虽然其对OPG基因转录的抑制作用不太明显,但是对RANKL基因转录和RANKL/OPG基因转录比率的调节与HE染色切片上骨溶解程度相一致。结论雷奈酸锶能够抑制小鼠颅骨骨溶解模型中TNF-α和RANKL的表达,并下调RANKL/OPG基因转录比率,从而抑制了由微粒诱导的骨溶解,为临床预防人工关节置换术后假体松动提供了理论依据。  相似文献   

2.
There is convincing evidence that particles produced by the wear of joint prostheses are causal in the peri-prosthetic loss of bone, or osteolysis, which, if it progresses, leads to the phenomenon of aseptic loosening. It is important to fully understand the biology of this bone loss because it threatens prosthesis survival, and loosened implants can result in peri-prosthetic fracture, which is disastrous for the patient and presents a difficult surgical scenario. The focus of this review is the bioactivity of polyethylene (PE) particles, since there is evidence that these are major players in the development and progression of osteolysis around prostheses which use PE as the bearing surface. The review describes the biological consequences of interaction of PE particles with macrophages, osteoclasts and cells of the osteoblast lineage, including osteocytes. It explores the possible cellular mechanisms of action of PE and seeks to use the findings to date to propose potential non-surgical treatments for osteolysis. In particular, a non-surgical approach is likely to be applicable to implants containing newer, highly cross-linked PEs (HXLPEs), for which osteolysis seems to occur with much reduced PE wear compared with conventional PEs. The caveat here is that we know little as yet about the bioactivity of HXLPE particles and addressing this constitutes our next challenge.  相似文献   

3.
《Acta orthopaedica》2013,84(5):446-451
Matrix metalloproteinases (MMPs) have been shown to play a role in aseptic loosening of total hip replacement (THR). Extracellular matrix metallo-proteinase inducer (EMMPRIN) can upregulate expression of several MMPs but has little effect on their tissue inhibitor (TIMP)- Using the avidin-biotin-per-oxidase complex immunostaining method, we detected strong immunoreactivity of EMMPRIN in the lining-like layers, sublining area and vascular endothelium of synovial membrane-like interface tissue around loosened prostheses. In contrast, EMMPRIN staining was very weak in the synovial samples from patients with hip arthrosis. Double immunofluorescence labeling revealed EMMPRIN/MMP-1 double-positive cells in iining-iike layers and the sublining area of interface tissue.

Our findings indicate that EMMPRIN expression is upregulated in interface tissue, and that locally accumulated EMMPRIN may modulate MMP-1 expression. An imbalance in the activity of MMPs and TIMP may lead to tissue destruction and periprosthetic osteolysis. These biological responses, combined with mechanical stress caused by micromotion and oscillating fluid pressure, may eventually cause aseptic loosening of THR.  相似文献   

4.
Matrix metalloproteinases (MMPs) have been shown to play a role in aseptic loosening of total hip replacement (THR). Extracellular matrix metalloproteinase inducer (EMMPRIN) can upregulate expression of several MMPs but has little effect on their tissue inhibitor (TIMP). Using the avidin-biotin-peroxidase complex immunostaining method, we detected strong immunoreactivity of EMMPRIN in the lining-like layers, sublining area and vascular endothelium of synovial membrane-like interface tissue around loosened prostheses. In contrast, EMMPRIN staining was very weak in the synovial samples from patients with hip arthrosis. Double immunofluorescence labeling revealed EMMPRIN/MMP-1 double-positive cells in lining-like layers and the sublining area of interface tissue. Our findings indicate that EMMPRIN expression is upregulated in interface tissue, and that locally accumulated EMMPRIN may modulate MMP-1 expression. An imbalance in the activity of MMPs and TIMP may lead to tissue destruction and periprosthetic osteolysis. These biological responses, combined with mechanical stress caused by micromotion and oscillating fluid pressure, may eventually cause aseptic loosening of THR.  相似文献   

5.
Matrix metalloproteinases (MMPs) have been shown to play a role in aseptic loosening of total hip replacement (THR). Extracellular matrix metallo-proteinase inducer (EMMPRIN) can upregulate expression of several MMPs but has little effect on their tissue inhibitor (TIMP)- Using the avidin-biotin-per-oxidase complex immunostaining method, we detected strong immunoreactivity of EMMPRIN in the lining-like layers, sublining area and vascular endothelium of synovial membrane-like interface tissue around loosened prostheses. In contrast, EMMPRIN staining was very weak in the synovial samples from patients with hip arthrosis. Double immunofluorescence labeling revealed EMMPRIN/MMP-1 double-positive cells in iining-iike layers and the sublining area of interface tissue.

Our findings indicate that EMMPRIN expression is upregulated in interface tissue, and that locally accumulated EMMPRIN may modulate MMP-1 expression. An imbalance in the activity of MMPs and TIMP may lead to tissue destruction and periprosthetic osteolysis. These biological responses, combined with mechanical stress caused by micromotion and oscillating fluid pressure, may eventually cause aseptic loosening of THR.  相似文献   

6.
目的通过观察局部注射VEGF及VEGF抗体对小鼠植骨气囊模型中磨损颗粒诱导骨溶解的影响,探讨VEGF在人工关节无菌性松动中的作用。方法取人工髋关节翻修术取出的金属关节假体柄,参照真空球磨法体外制备磨损颗粒,PBS配制成浓度为10 mg/mL颗粒悬液。取8~10周龄雌性昆明小鼠50只,体重约25 g。10只作为气囊植骨模型颅骨供体。剩余40只小鼠随机分为4组(n=10),分别为空白对照组(A组)、颗粒组(B组)、VEGF刺激组(C组)和VEGF抑制组(D组);小鼠背部皮下注射无菌空气制备气囊,第8天切开气囊植入颅骨骨片,制备植骨气囊模型。于植骨后第1天B、C、D组气囊内注入0.5 mL颗粒悬液,A组注入0.5 mL PBS。气囊制备期间第6、7天及植骨后隔天,C、D组气囊内分别注射0.2 mL重组人VEGF和Bevacizumab溶液,A、B组注射0.2 mL生理盐水。植骨2周后取囊壁连同骨片行HE染色、实时荧光定量PCR及ELISA检测。结果各组小鼠均存活至实验完成。大体观察见A组气囊红肿程度轻,新生血管少;B、C、D组气囊明显红肿,可见较多渗出及新生血管,其中C组最重,B组次之,D组介于A、B组间。组织学及分子生物学检测发现,B组囊壁明显炎性反应及骨溶解,囊壁厚度、细胞密度及TNF-α、IL-1β、VEGF表达均较A组明显增加(P<0.05);C组囊壁炎性反应及骨溶解最显著,以上观察指标均高于B组(P<0.05);D组囊壁亦可见炎性反应及骨溶解,但以上指标均低于B组(P<0.05),高于A组(P<0.05)。结论 VEGF在人工关节无菌性松动中具有促进炎性反应及骨溶解作用,局部给予VEGF抗体可抑制磨损颗粒诱导的骨溶解。  相似文献   

7.
Research results have been contradictory about the role of lymphocytes and immune response in aseptic loosening of total hip replacement (THR). Conclusive evidence is still lacking in spite of extensive in vivo and in vitro studies. Our study was designed to check whether T-cells were activated and if they produced lymphokines in synovial membrane-like interface tissue around loosened THRs. Tissue sections were stabilized and permeabilized to allow the cytokine-specific antibodies to penetrate through the cell membrane and the membranes of intracellular organelles. This technique, combined with computer-assisted image analysis, permits the detection and quantitation of lymphokine-producing cells. We found that the number of T-cells was low, and none of the T-cells was activated, as shown by the absence of interleukin-2 receptor (IL-2R) immunoreactivity. There was no cell producing lymphokines, such as interleukin-2 (IL-2), interferon-gamma (IFN-^7;), and tumor necrosis factor-beta (TNF-^6;). Our results suggest that T-cell-mediated immune response is not actively involved in aseptic loosening of THR.  相似文献   

8.
9.
目的人工关节无菌性松动与破骨细胞激活后假体周围骨溶解有关,而NF-κB受体激活因子配体(receptor activator of NF-κB ligand,RANKL)/NF-κB受体激活因子(receptor activator of NF-κB,RANK)信号通路是激活破骨细胞的主要途径,通过建立小鼠气囊植骨模型模拟人工关节无菌性松动环境,观察RANKL抗体抑制炎性反应、减轻溶骨反应的作用。方法取8~10周龄雌性BALB/c小鼠60只(体重18~20 g),取其中20只小鼠颅骨制备骨片,作为气囊植骨供体;剩余40只小鼠随机分为阴性对照组(A组)、阳性对照组(B组)、RANKL抗体低剂量组(C组)和RANKL抗体高剂量组(D组),每组10只。于各组小鼠背部制备2 cm×2 cm大小的气囊后植入1片骨片;于植骨后1 d,A组气囊内注射0.5 mL PBS液;B、C、D组注射0.5 mL钛颗粒悬液。钛颗粒悬液注射前2 d,C、D组气囊内分别注射0.1 mL浓度为50μg/mL和500μg/mL的RANKL抗体,每天1次,连续2 d;A、B组注射0.1 mL PBS液。于植骨后14 d处死全部小鼠,取出植入颅骨骨片和周围囊壁组织,进行大体及组织学观察,并行颅骨骨溶解、骨胶原含量及破骨细胞含量分析。结果各组小鼠均存活至实验完成,切口愈合良好。大体观察见A、C、D组小鼠囊壁炎性反应较轻,偶见渗出和新生血管增生;B组炎性反应严重,见渗出以及新生血管增生。组织学观察见A、C、D组小鼠囊壁炎性细胞浸润及增厚不明显,骨胶原丢失量和破骨细胞含量少;B组大量炎性细胞浸润,囊壁增厚,骨胶原丢失量和破骨细胞含量多。B组炎性细胞数、囊壁厚度、骨胶原丢失量以及破骨细胞含量与A、C、D组比较,差异均有统计学意义(P<0.05)。结论 RANKL抗体可阻断小鼠气囊植骨模型的炎症信号传导通路,有效抑制磨损颗粒所致骨溶解。  相似文献   

10.
PURPOSE: Both macrophages and fibroblasts are the main cell types found in periprosthetic tissues surrounding failed joint arthroplasties. These fibroblasts are known to express RANKL and to produce TNFalpha, factors which promote osteoclast formation and bone resorption. In this study we have analysed the role that arthroplasty membrane-derived fibroblasts (AFb) play in inducing the generation of bone resorbing osteoclasts. METHODS: Fibroblasts were isolated from periprosthetic tissues and co-cultured with human monocytes in an osteoclast differentiation assay in the presence or absence of M-CSF and inhibitors of RANKL (OPG) and/or TNFalpha. RANKL expression by AFbs was determined by RT-PCR and the extent of osteoclast differentiation by the expression of TRAP, VNR and evidence of lacunar resorption. RESULTS: In the presence of M-CSF, large numbers of TRAP(+) and VNR(+) multinucleated cells capable of lacunar resorption, were noted in co-cultures of monocytes and RANKL-expressing AFbs. Cell-cell contact was required for osteoclast formation. The addition of OPG and anti-TNFalpha alone significantly reduced but did not abolish the extent of osteoclast formation, whereas the addition of both together abolished osteoclast formation and lacunar resorption. CONCLUSION: Our results indicate that fibroblasts in periprosthetic tissues are capable of inducing the differentiation of normal human peripheral blood mononuclear cells to mature osteoclasts by a mechanism that involves both RANKL and TNFalpha. Suppression of both RANKL and inflammatory cytokines is likely to be required to control periprosthetic osteolysis.  相似文献   

11.
目的对磨损颗粒引发假体周围骨溶解的机制及药物治疗进展进行了综述介绍。方法对国外近期相关文献进行综述。结果及结论人工关节置换是治疗晚期骨关节炎及老年股骨颈骨折的有效方法,能达到解除关节疼痛、重建活动功能及提高生活质量的目的。人工关节无菌性松动是影响人工关节使用寿命和远期疗效的最重要的并发症。磨损颗粒诱发假体周围组织细胞产生一系列生物学反应是导致假体周围骨溶解及假体无菌性松动的重要因素。磨损颗粒刺激假体周围的巨噬细胞、成骨细胞、成纤维细胞等产生多种细胞因子,形成破骨细胞性骨吸收,同时影响成骨细胞的分化及功能,抑制骨形成。药物在预防和治疗磨损颗粒引起的人工关节松动方面能起到积极的作用。  相似文献   

12.
In the conventional method of microskin autografting, aggressive early excision is adopted, followed by coverage with a microskin–allograft complex to close extensive burn wounds. However, early excision is always associated with a defect of viable tissue, resulting in massive blood loss and causing high risk to aged patients or those with other systemic diseases. We developed a new method in which an eschar thinning operation was first adopted, followed by raising granulation tissue and microskin autografting, which was covered by a Vaseline-based moisture dressing. A total of 52 patients were included in this study and randomly assigned to the control group (n = 26) and the experimental group (n = 26) for the conventional method and the new method, respectively. The re-epithelisation rate on the 21st day after autografting indicated that there was no significant difference between both groups. There was also no significant difference between the two groups when the re-epithelialisation rate was compared with the type of organisms cultured. However, the Vancouver Burn Skin Score (VBSS) results demonstrated a significant improvement of cosmetic appearance in the experimental group (score = 2.1) as compared to the control group (score = 3.9). The new method also showed other advantages, including less blood loss, shorter surgical duration and lower cost of surgery. From this prospective study, it can be concluded that the new method can be an alternative to the conventional microskin autografting procedure.  相似文献   

13.
目的分析糖尿病足感染对患者创面肉芽组织细胞自噬相关蛋白表达的影响,为治疗糖尿病足感染提供理论依据。 方法选取自2013年1月至2017年7月恩施土家族苗族自治州中心医院接诊的88例糖尿病足感染者为研究对象,将正处于感染期44例患者作为观察组,将感染控制后44例患者作为对照组。根据踝肱指数(ABI)分组:观察组患者中20例缺血患者作为缺血组,24例非缺血患者作为非缺血组。提取患者创面组织,进一步处理后采用免疫组织化学染色和蛋白质印迹法进行检测,观察记录患者的姓名、年龄、身高、体重、病程等基本信息,密切观察患者病情变化,详细记录患者创面组织细胞自噬蛋白微管结合轻链蛋白-3(LC3)、自噬特异性基因(Beclin-1)和泛素结合蛋白(p62)等指标。 结果免疫组织化学染色法显示:观察组患者LC3和Beclin-1水平均显著低于对照组患者(t= 3.638、P = 0.011,t = 2.682、P= 0.022),p62水平高于对照组患者(t = 4.998、P = 0.009),差异均有统计学意义。非缺血组患者LC3和Beclin-1水平均显著高于缺血组患者(t= 2.837、P = 0.018,t = 3.028、P = 0.012),p62水平低于缺血组患者(t = 3.562,P= 0.010),差异均有统计学意义。观察组患者Beclin-1灰度值低于对照组,差异有统计学意义(t = 3.522,P= 0.013),而p62灰度值高于对照组,差异有统计学意义(t = 6.927、P= 0.004);两组患者LC3灰度值差异无统计学意义(t = 1.037、P= 0.056)。 结论糖尿病足感染会导致患者细胞自噬水平降低,合并缺血患者细胞自噬水平进一步降低,糖尿病足感染控制后,细胞自噬水平升高。  相似文献   

14.
磨损微粒在无菌性松动关节假体周围迁移聚积的实验研究   总被引:1,自引:0,他引:1  
目的 观察人工髋关节假体周围界膜的超微结构 ,了解磨损微粒的形态及其在人工髋关节假体周围迁移聚积的特征。方法 临床选取 4例人工全髋关节术后发生无菌性松动病例 ,于翻修术中按照Delee Charnley髋臼分区法和Gruen Amstutz股骨分区法采取假体周围界膜组织 ,以透射电镜进行观察 ,统计各区磨损微粒数目。结果 界膜组织标本含有大量胶原纤维 ,其间可见大量黑色磨损微粒。其中髋臼分区三区磨损微粒聚积数明显高于一区和二区 (P <0 0 5 ) ,股骨分区中一区、七区中磨损微粒明显高于其余各区 (P <0 0 5 )。结论 磨损微粒的产生、迁移和局部聚积具有一定特征和规律性  相似文献   

15.
MicroRNA在无菌性松动中的研究进展   总被引:2,自引:2,他引:0  
刘国印  王瑞  赵建宁 《中国骨伤》2014,27(3):232-236
MicroRNA(miRNA)是一种非编码的小分子RNA,在基因的表达调控过程中起着非常重要的作用。近年来,miRNA在疾病发生发展过程中的作用已成为研究的热点。磨损微粒诱导的持续性炎症反应以及破骨细胞的增殖分化或成骨细胞分化成熟的减少是无菌性松动发生过程中的重要因素。而最新研究表明,持续性炎症反应,成骨细胞、破骨细胞的分化与miRNA有着密切的关联,提示miRNA在无菌性松动的发生发展中起重要作用,改变相关miRNA的表达水平也能对其起到治疗作用。随着miRNA新的靶点的研究发现,其重要作用进一步被证实。  相似文献   

16.
输尿管镜钬激光碎石治疗210例输尿管息肉包裹性结石   总被引:1,自引:0,他引:1  
目的探讨经输尿管镜钬激光碎石术治疗输尿管息肉包裹性结石的疗效。方法收集本院2003年12月至2009年6月期间经输尿管镜钬激光碎石术治疗输尿管息肉包裹性结石210例病例资料,进行回顾性分析。其中,男139例,女71例,年龄17~69岁,单侧202例,双侧8例,结石直径0.8~2.1cm。结果手术成功率89%(187/210),结石直径8~17mm,平均手术时间67±24min,住院时间5~9d,结石排净平均时间19.7±11.3d。碎石失败23例,其中结石体积较大导致碎石不理想4例;输尿管狭窄或者扭曲造成置镜失败或者碎石不理想13例;结石移位被冲入肾盂6例。并发症发生率9%,其中,输尿管口或壁段损伤11例,输尿管穿孔或假道6例,肾周积液并感染1例,输尿管完全撕脱1例。结论经输尿管镜钬激光碎石术治疗输尿管肉芽包裹性结石是一种相对高效、安全的治疗手段。  相似文献   

17.
To establish the types of wear particles and associated tissue response around human prostheses the periprosthetic tissues around 50 hip arthroplasties revised for aseptic loosening of one or more components were examined by light microscopy, transmission electron microscopy, and energy-dispersing x-ray microanalysis. The tissues around cementless metal-on-bone and ceramic-on-ceramic prostheses contained few or no prosthesis wear particles. The tissues around metal-on-metal prostheses contained large numbers of metal particles and large numbers of macrophages, and occasional multinucleate giant cells. The tissues around cemented metal-on-polyethylene prostheses often contained large numbers of small and large polyethylene particles, variable numbers of cement particles, and occasional metal particles. Large numbers of macrophages and multinucleate giant cells were frequently seen in these tissues. Lymphocytes were occasionally seen in association with metal particles. Ultrastructural studies of the periprosthetic tissues confirmed the phagocytosis of submicroscopic wear particles by macrophages. Varying degrees of degenerative change in macrophages were seen in association with phagocytosis of metal particles. Large numbers of cytolysosomes were seen in cells in association with the accumulation of wear particles.  相似文献   

18.
FE复合酶防治烧伤后期肉芽创面感染的临床观察   总被引:2,自引:1,他引:1  
目的观察FE复合酶控制烧伤后期肉芽创面常见耐药菌感染的作用。方法选取笔者单位烧伤患者30例,随机分为治疗组15例,将FE复合酶50 ml溶于等渗盐水0-150 ml中,使其终浓度为1-3 U/ml,用无菌纱布浸湿该液后湿敷创面,1-2次/d;对照组15例,用庆大霉素+ 等渗盐水纱布湿敷创面,1-2次/d。于用药前及用药后1-5 d取创面分泌物作细菌培养,检测两组患者创面的细菌种类及所用药物对创面细菌的敏感率;观察两组患者创面愈合时间及植皮术后3、5、 8、10、12 d的创面愈合率。结果两组患者创面细菌以铜绿假单胞菌、大肠杆菌、阴沟肠杆菌、甲氧西林耐药金黄色葡萄球菌(MRSA)为主。治疗组对MRSA、表皮葡萄球菌、腐生葡萄球菌、铜绿假单胞菌、大肠杆菌、阴沟肠杆菌的敏感率分别为93.8%、100.0%、100.0%、100.0%、100.O%、95.0%,高于对照组的17.6%、31.3%、28.6%、44.0%、33.3%、28.0%(P<0.01)。治疗组植皮术后创面愈合时间为(10.6±1.5)d,明显短于对照组[(15.3±1.7)d,P<0.01]。治疗组患者植皮术后各时相点创面愈合率均明显高于对照组(P<0.01),植皮术后10 d治疗组创面愈合率为(85.4±2.4)%,与对照组(51.3±1.5)%比较,差异有统计学意义(P<0.01)。结论 FE复合酶可以有效控制创面感染,提高烧伤后期感染创面植皮成功率。  相似文献   

19.
目的:研究唑来膦酸钠( ZOL)对钛颗粒诱导的骨溶解的影响。方法分离6~8周C57BL/6J小鼠长骨中的前体破骨细胞( OCP)并分为6组,A组:OCP+细胞培养液,B组:OCP+巨噬细胞集落刺激因子(M-CSF)+NF-κB 受体活化因子配体(RANKL)+细胞培养液,C组:OCP+钛颗粒+细胞培养液,D组:OCP+上清液(钛颗粒刺激巨噬细胞24 h后上清液)+细胞培养液,E组:OCP+M-CSF+RANKL+ZOL+细胞培养液,F组:OCP+上清液+ZOL+细胞培养液。每组细胞分别接种在玻璃盖玻片、皮质骨磨片和含骨检测表面的96孔板上,10 d后检测玻璃盖玻片上细胞抗酒石酸磷酸酶( TRAP)的表达及皮质骨磨片上骨吸收陷窝的形成,并以骨检测表面的骨吸收面积为指标比较各组破骨细胞的骨吸收活性。结果 B组、D组、E组和F组的OCP均能分化为能被TRAP染色成阳性的破骨细胞并形成骨吸收陷窝,其余组均未发现TRAP染色阳性的破骨细胞和骨陷窝。加入ZOL的F组骨吸收面积(5.54%±1.25%)较D组(10.34%±1.69%)明显减少,差异具有统计学意义(t=5.61,P<0.01)。结论在体外实验中钛颗粒并不能直接刺激前体破骨细胞向破骨细胞转化;唑来膦酸钠可以抑制钛颗粒诱导的骨溶解作用。  相似文献   

20.
文立成  李军  马忠泰 《中华外科杂志》2009,47(24):1888-1891
目的 对H/G非骨水泥人工全髋关节置换术后聚乙烯内杯的磨损及髋臼周围骨溶解的情况进行总结.方法 我院1991至1995年共进行58例(65髋)H/G非骨水泥人工全髋关节置换,其中35例(40髋)获得10年以上随访.对这35例(40髋)患者获得随访的病例,采用计算机数字化方法测量髋臼聚乙烯内杯的二维线性磨损.结果 35例40髋均有不同程度的磨损,磨损范围2~8 mm,平均磨损为(0.32±0.31)mm/年.10髋聚乙烯磨损超过6 mm,髋臼假体周围的骨溶解严重,并伴有金属假体的移位,其中5髋聚乙烯内杯完伞磨透,金属股骨头与金属髋臼相接触;5髋聚乙烯内杯磨损严重伴明显骨溶解,内杯松动.2髋聚乙烯内杯脱位.共实施翻修手术12例,包括更换聚乙烯内杯和金属股骨头2例、金属闩杯翻修2例、全髋翻修8例.28髋在髋臼侧发现骨溶解,其中14髋股骨侧亦有骨溶解发生.结论 本组病例所观测到的H/G髋臼聚乙烯内杯的磨损程度超过文献所报道,而且由于磨损产生的大量磨屑,导致假体周围出现明显骨溶解,直接影响到假体的稳定.关节置换术后应定期随访,避免出现严重骨溶解后增加翻修手术的困难.  相似文献   

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