Background:Segmental bone defect is a challenging clinical problem that often requires autologous bone grafting, which has limitations such as donor site morbidity and insufficient supply. Bone tissue engineering aims to create functional bone substitutes that can mimic the properties and processes of native bone. However, the discrepancy between in vitro and in vivo conditions hinders the successful translation of bone tissue engineering from animal models to human applications. Organoids, such as muscle pouch-based models, are emerging as promising tools that can closely resemble the osteogenic niche and overcome some of the limitations of conventional in vitro models. Methods:In this study, we explored two distinct muscle-biomaterial based bone induction models: an in vivo heterotopic implantation model and a novel ex vivo muscle pouch-based coral-derived macroporous construct organoid model. They both utilized the coral-derived constructs, specifically 13 % hydroxyapatite/calcium carbonate (13 % HA/CC) as the biomaterial. We implanted 72 coral-derived devices into rats' rectus abdominis muscle, divided equally between in vivo and ex vivo groups. Samples were harvested at 15, 30, and 60 days for molecular and histological analyses. We assessed the relative gene expression of angiogenesis markers (Vegfa and Col4a1) and osteogenesis signaling and structural markers (Runx2, Bmp2, Ocn and Alp) using qRT-PCR. We analyzed tissue morphogenesis, angiogenesis and induction of bone formation by H&E and modified Goldner's Trichrome staining. Immunostaining was further used to detect the expression and localization of OCN, VEGFA and CD31 in both in vivo and ex vivo models. Results:We demonstrated that ex vivo muscle pouch-based coral-derived macroporous construct organoid model supported tissue survival up to 60 days with compromised tissue ingrowth compared to the in vivo model. Primary vascular structures formed at the tissue-scaffold interface in the organoid system with persistent up-regulation of Vegfa and Col4a1, while comprehensive angiogenesis took place with early up-regulation of Vegfa and Col4a1 in vivo. Proper bone formation was absent in both the ex vivo and in vivo models, but the in vivo models showed an up-regulation of Bmp2 and Alp in early phase and a delayed Ocn expression on day 30. The ex vivo model showed connective tissue formation, comprehensive OCN deposition, and gene expression patterns mimicking in vivo trends but with some distinctions. Conclusions:The ex vivo muscle pouch-based coral-derived macroporous construct organoid model in this study can partially recapitulate angiogenesis and osteogenesis as compared to the in vivo model. However, key molecular signaling events that regulate these processes remained inactive. The study demonstrated that activating these events could enable the establishment of an ex vivo tissue-based vascularized model. The translational potential of this article:This study partly elucidated the molecular signaling events involved in the development of an ex vivo tissue-based osteogenic organoid that closely resembled its in vivo counterpart. This would facilitate the development of well vascularized artificial bone grafts for treating segmental bone defects.
The migration and clogging of fine particles in the pores of coarse-grained soil with seepage is of great significance to reduce the leakage of soil at the dam base and lower the permeability of soil. Therefore, the homemade infiltration test device was used to test the infiltration and clogging of soil samples with different particle size ratios D 15 / d 85 ( D 15 represents the particle size corresponding to the cumulative percentage content of soil particles smaller than a certain particle size in the coarse particles which is 15%, and d 85 represents the particle size corresponding to the cumulative percentage content of soil particles smaller than a certain particle size in the fine particles group which is 85%). The factors affecting the deposition of fine particles in coarse-grained soil and the characteristics of fine particle migration and penetration were analyzed. The clogging of coarse-grained soil, hydraulic gradient and pore changes characteristics before and after clogging were studied. The results show that: 1) The main factor affecting the retention of fine particles in coarse-grained soil is the particle size ratio, and the retention rules conforms to the Peak-Gauss function relationship. The penetration law of fine particles satisfies the Logistic function relationship, which can directly predict the internal clogging of coarse-grained soil. 2) The particle size ratio is the main factor affecting the blockage in each mode, followed by the influence of the water head, When the particle size ratio is less than 13.10, the clogging ratio decreases with the increase of particle size ratio, and the hydraulic gradient increases with the increase of particle size ratio. When is greater than 13.10, the clogging ratio increases with the increase of particle size ratio, and the hydraulic gradient decreases with the increase of particle size ratio. 3) The degree of clogging in coarsegrained soil is closely related to the change in porosityand and can be judged according to the change of porosity in coarse-grained soil. The research results deepen the understanding of fine particle migration on the rules of coarse-grained soil clogging and can provide a theoretical basis for related engineering applications.
The dam anti-seepage body with cohesive soil as the main source often has perforated cracks due to extreme temperature difference, uneven settlement and other reasons, which eventually induces seepage failure. Hydraulic filling and clogging is an economical and effective repair method. In order to understand its repair mechanism, this paper takes the remolded cohesive soil as the research object, prefabricates cracks in the soil to simulate the cracking of the impermeable body, and studies the effects of muddy water concentration, water head, seepage direction (i.e. horizontal, vertical, oblique), non-uniformity coefficient of the filter layer and other factors on crack repair. The motion state of the fluid in the crack during crack repair was determined, and the evolution law of the crack under the action of muddy water seepage was studied based on digital image processing technology. The results show that under the action of muddy water seepage, the crack repair process in cohesive soil can be divided into three stages: transition period (stage 1), repair period (stage 2) and stable period (stage 3). The crack repair process will affect the seepage characteristics of the fluid in the crack. The fluid motion law at stages 1 and 2 satisfies the Forchheimer flow, and the fluid motion law at stage 3 conforms to the Darcy flow. The starting point of stage 3 is the critical point of flow transition, and the stage of fracture repair can be judged according to the change of flow state in the crack. Muddy water concentration, water head, crack type and uneven coefficient of filter layer are the main influencing factors of crack repair. The time required for crack repair is the shortest under high muddy water concentration and low water head. The seepage quantity Q and flow velocity v after the crack repair are significantly lower than those before the repair, which are reduced by 99.83% and 99.98%, respectively, while the hydraulic gradient J is significantly increased by 27.92 times, and the impermeability performance of the soil after the repair is significantly enhanced. The research has certain theoretical guidance value for the evolution mechanism and prevention measures of the cracks in the dam anti-seepage body.
INTRODUCTION:Fractures of the anterior process of the calcaneus (APC) are easily overlooked in clinical practice. Most patients have good to excellent clinical outcome after conservative treatment, while some patients may have persisting symptoms and unfavorable functional outcomes. The aim of this study was to identify the risk factors associated with unfavorable functional outcome after conservative treatment in APC fractures. METHODS:All patients presenting with APC fractures and receiving conservative treatment from April 2019 to April 2020 were retrospectively assessed. The primary outcome measurement was the ankle joint function assessed using Karlsson Scoring System at 2 years post-injury. The risk factors associated with unfavorable functional outcomes (Karlsson score ≤ 80) were evaluated by logistic regression analysis. RESULTS:In total, 84 patients were included with a mean age of 40 years. 26 (31%) patients presented with unfavorable functional outcome at 2 years post-injury. In multivariate logistic regression, concomitant fractures of talonavicular (TN) joints and older age were significantly associated with unfavorable functional outcome (p<0.05). Patients with concomitant fractures of TN joints had an odds ratio of 3.623 for unfavorable functional outcome. The optimal cutoff age for an unfavorable outcome was ≥ 47.5 years, with an odds ratio of 5.010. CONCLUSION:Most patients with APC fractures achieved good to excellent results when treated conservatively. Attention should be paid to those with concomitant fractures of TN joints and with age ≥ 47.5 years, which might lead to unfavorable functional recovery. LEVEL OF EVIDENCE:IV; case series.
Fractures of the anterior process of the calcaneus (APC) are easily overlooked in clinical practice. Most patients have good to excellent clinical outcome after conservative treatment, while some patients may have persisting symptoms and unfavorable functional outcomes. The aim of this study was to identify the risk factors associated with unfavorable functional outcome after conservative treatment in APC fractures. All patients presenting with APC fractures and receiving conservative treatment from April 2019 to April 2020 were retrospectively assessed. The primary outcome measurement was the ankle joint function assessed using Karlsson Scoring System at 2 years post-injury. The risk factors associated with unfavorable functional outcomes (Karlsson score≤80) were evaluated by logistic regression analysis. Eighty-four patients were included with a mean age of 40 years. Twenty-six (31 %) patients presented with unfavorable functional outcome at 2 years post-injury. In multivariate logistic regression, concomitant fractures of talonavicular (TN) joints and older age were significantly associated with unfavorable functional outcome (p < 0.05). Patients with concomitant fractures of TN joints had an odds ratio of 3.623 for unfavorable functional outcome. The optimal cutoff age for an unfavorable outcome was ≥ 47.5 years, with an odds ratio of 5.010. Most patients with APC fractures achieved good to excellent results when treated conservatively. Attention should be paid to those with concomitant fractures of TN joints and with age ≥ 47.5 years, which might lead to unfavorable functional recovery. IV; Case series.
Background Fractures of the lateral process of the talus (LTPF) are rare and only rarely are associated ligamentous injuries. The injury mechanism is commonly considered to be similar with ankle sprains, where excessive varus of the hindfoot leads to avulsion fractures of the lateral process of the talus. However, previous cadaveric studies have suggested that LTPF was more likely to be caused by eversion or external rotation force with dorsiflexion of the ankle. But no clinical evidence has been provided. Case presentation Two patients presented to the emergency department with ankle pain after ankle eversion or external rotation. Physical examination revealed tenderness and swelling on both medial and lateral sides of the ankles. Plain radiographs and computed tomography revealed LTPF and medial soft tissue swelling, and magnetic resonance imaging confirmed a discontinuity of the deltoid ligament in Case 1. Surgical exploration revealed rupture of the superficial layer of the deltoid ligaments with intact deep layer in both patients. Treatment included fixation of the lateral process of the talus with headless compression screws and repair of deltoid ligaments. Both patients achieved excellent clinical outcomes 1 year post injury. Conclusion There are many possibilities of the injury mechanism of LTPF. These two cases provided clinical evidence that eversion or external rotation force, in addition to inversion, was also an important mechanism of LTPF.
Background: Diverse conclusions have been drawn regarding the association of homocysteine (HCY) deficiency and supplements of B vitamins with fracture incidence in older adults. The aim of this meta-analysis was to investigate the association of HCY and B vitamins (folate, vitamin B12, and B6) with fracture incidence in older adults and whether supplements of B vitamins reduce the risk of fracture. Methods: The PubMed, Embase, and Cochrane library databases were systematically searched from their inception dates to 1 July 2019 to identify relevant published articles. Meta-analysis was performed to pool hazard ratios (HRs) or risk ratios (RRs) and 95% confidence intervals (CIs) using a random effects model. Results: A total of 28 studies fulfilled the inclusion criteria. High serum HCY was an independent risk factor for fractures in older persons (HR =1.25, 95% CI: 1.12 to 1.40), but only at the highest quartile level (>15 mu mol/L) (HR =1.71, 95% CI: 1.37 to 2.12), rather than the second and third quartile. Multiple sensitivity and subgroup analyses supported the consistency and stability of this result. A severe deficiency of folate, instead of vitamin B12 and B6, was found to increase the risk of fracture in older adults (HR =1.46, 95% CI: 1.06 to 2.02; 1.24, 95% CI: 0.79 to 1.95; 1.36, 95% CI: 0.90 to 2.06, respectively). For the interventional effect, there was no significant association of combined folate and vitamin B12, combined folate, vitamin B12 and B6, or single vitamin B6 supplementation with the decrease of fracture risk. Discussion: This meta-analysis revealed that significantly elevated serum level of HCY is positively associated with fracture incidence in older adults, yet the necessity and threshold for intervention by B vitamins require further large-scale high-quality clinical trials to validate. PROSPERO identifier: CRD42019122586.
Background Diverse conclusions have been drawn regarding the association of homocysteine (HCY) deficiency and supplements of B vitamins with fracture incidence in older adults. The aim of this meta-analysis was to investigate the association of HCY and B vitamins (folate, vitamin B12, and B6) with fracture incidence in older adults and whether supplements of B vitamins reduce the risk of fracture. Methods The PubMed, Embase, and Cochrane library databases were systematically searched from their inception dates to 1 July 2019 to identify relevant published articles. Meta-analysis was performed to pool hazard ratios (HRs) or risk ratios (RRs) and 95% confidence intervals (CIs) using a random effects model. Results A total of 28 studies fulfilled the inclusion criteria. High serum HCY was an independent risk factor for fractures in older persons (HR =1.25, 95% CI: 1.12 to 1.40), but only at the highest quartile level (>15 µmol/L) (HR =1.71, 95% CI: 1.37 to 2.12), rather than the second and third quartile. Multiple sensitivity and subgroup analyses supported the consistency and stability of this result. A severe deficiency of folate, instead of vitamin B12 and B6, was found to increase the risk of fracture in older adults (HR =1.46, 95% CI: 1.06 to 2.02; 1.24, 95% CI: 0.79 to 1.95; 1.36, 95% CI: 0.90 to 2.06, respectively). For the interventional effect, there was no significant association of combined folate and vitamin B12, combined folate, vitamin B12 and B6, or single vitamin B6 supplementation with the decrease of fracture risk. Discussion This meta-analysis revealed that significantly elevated serum level of HCY is positively associated with fracture incidence in older adults, yet the necessity and threshold for intervention by B vitamins require further large-scale high-quality clinical trials to validate. PROSPERO identifier CRD42019122586.
Background Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) remains one of the best-established techniques to assess gene expression patterns. However, appropriate reference gene(s) selection remains a critical and challenging subject in which inappropriate reference gene selction can distort results leading to false interpretations. To date, mixed opinions still exist in how to choose the most optimal reference gene sets in accodrance to the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guideline. Therefore, the purpose of this study was to investigate which schemes were the most feasible for the identification of reference genes in a bone and cartilage bioengineering experimental setting. In this study, rat bone mesenchymal stem cells (rBMSCs), skeletal muscle tissue and adipose tissue were utilized, undergoing either chondrogenic or osteogenic induction, to investigate the optimal reference gene set identification scheme that would subsequently ensure stable and accurate interpretation of gene expression in bone and cartilage bioengineering. Results The stability and pairwise variance of eight candidate reference genes were analyzed using geNorm. The V 0.15 - vs. V min -based normalization scheme in rBMSCs had no significant effect on the eventual normalization of target genes. In terms of the muscle tissue, the results of the correlation of NF values between the V 0.15 and V min schemes and the variance of target genes expression levels generated by these two schemes showed that different schemes do indeed have a significant effect on the eventual normalization of target genes. Three selection schemes were adopted in terms of the adipose tissue, including the three optimal reference genes (Opt 3 ), V 0.20 and V min schemes, and the analysis of NF values with eventual normalization of target genes showed that the different selection schemes also have a significant effect on the eventual normalization of target genes. Conclusions Based on these results, the proposed cut-off value of Vn/n + 1 under 0.15, according to the geNorm algorithm, should be considered with caution. For cell only experiments, at least rBMSCs, a Vn/n + 1 under 0.15 is sufficient in RT-qPCR studies. However, when using certain tissue types such as skeletal muscle and adipose tissue the minimum Vn/n + 1 should be used instead as this provides a far superior mode of generating accurate gene expression results. We thus recommended that when the stability and variation of a candidate reference genes in a specific study is unclear the minimum Vn/n + 1 should always be used as this ensures the best and most accurate gene expression value is achieved during RT-qPCR assays.
Background: For proximal humeral fractures (PHFs), locking intramedullary nails and locking plates have been widely used. However, few reports have been published on the therapy of complex PHFs accompanying humeral shaft fractures. Therefore, we performed this research to analyze the effectiveness of locking intramedullary nails and locking plates in the management of proximal humeral fractures involving the humeral shaft. Material/Methods: We retrospectively reviewed 40 cases diagnosed with proximal humeral fractures involving the humeral shaft fixed with either locking intramedullary nails or locking plates with at least of 2 years' follow-up. Clinical data were obtained from the medical records. Follow-up data included the Constant-Murley score, American Shoulder and Elbow Surgeons score (ASES), visual analog scale score (VAS), and the relative strength of the supraspinatus and deltoid muscles. Results: In total, 19 locking plate patients and 21 locking intramedullary nail patients were analyzed. The average follow-up period was 35 months in the locking plate group and 34 months in the locking intramedullary nail group. There were obvious differences in the intraoperative blood loss, time of operation, and the length of operative incision between the 2 groups (p<0.05). There were no significant differences between the groups in Constant-Murley score, ASES, VAS, or the relative strength of supraspinatus and deltoid muscles. Conclusions: For PHFs involving the humeral shaft, both locking plates and locking intramedullary nails can achieve satisfactory functional results in the long-term follow-up assessment. The locking intramedullary nail group was superior with regards to intraoperative blood loss, time of operation, and length of incision.
Background The translation from animal research into the clinical environment remains problematic, as animal systems do not adequately replicate the human in vivo environment. Bioreactors have emerged as a good alternative that can reproduce part of the human in vivo processes at an in vitro level. However, in vitro bone formation platforms primarily utilize stem cells only, with tissue based in vitro systems remaining poorly investigated. As such, the present pilot study explored the tissue behavior and cell survival capability within a new in vitro skeletal muscle tissue-based biomaterial organoid bioreactor system to maximize future bone tissue engineering prospects. Results Three dimensional printed β-tricalcium phosphate/hydroxyapatite devices were either wrapped in a sheet of rat muscle tissue or first implanted in a heterotopic muscle pouch that was then excised and cultured in vitro for up to 30 days. Devices wrapped in muscle tissue showed cell death by day 15. Contrarily, devices in muscle pouches showed angiogenic and limited osteogenic gene expression tendencies with consistent TGF-ß 1 , COL4A1 , VEGF-A , RUNX-2 , and BMP-2 up-regulation, respectively. Histologically, muscle tissue degradation and fibrin release was seen being absorbed by devices acting possibly as a support for new tissue formation in the bioceramic scaffold that supports progenitor stem cell osteogenic differentiation. Conclusions These results therefore demonstrate that the skeletal muscle pouch-based biomaterial culturing system can support tissue survival over a prolonged culture period and represents a novel organoid tissue model that with further adjustments could generate bone tissue for direct clinical transplantations.
背景:多项体外细胞学实验显示,含氧化涂层钛金属较普通钛金属表面表现出更好的生物相容性和生物活性。目的:进一步观察等离子体电解氧化涂层钛棒在动物体内的骨整合能力。方法:取36只16周龄雄性SD大鼠(购自上海西普尔-必凯实验动物有限公司),建立双侧股骨远端髓内钉植入模型,左侧植入多孔纳米等离子体电解氧化涂层钛棒,作为实验组;右侧植入无涂层钛棒,作为对照组。植入2,4,6周时,处死大鼠并收获股骨远端带有金属植入物的骨组织标本,进行Van Gieson染色、双标荧光染色及生物力学评价。结果与结论:(1)Van Gieson染色显示,实验组与对照组植入物-骨组织界面均未见纤维组织长入;植入2周时,两组均可见植入物表面部分骨组织接触,实验组于植入4周时形成植入物周围骨整合,对照组于植入6周时形成植入物周围骨整合;(2)双标荧光染色显示,植入2周时,两组植入物周围均产生大量新生骨组织,与钛棒结合紧密;植入4周时,实验组新生骨与植入物表面呈现连续性接触,对照组新生骨与植入物表面呈不连续区块接触;植入6周时,两组均显示出了连续的植入物-骨组织接触,但新生骨骨量明显较4周时减少;(3)生物力学检测显示,实验组植入4周时的最大压缩载荷高于对照组(P <0.001),两组植入2,6周时的最大压缩载荷比较无差异(P> 0.05);实验组植入4周时的最大压缩载荷高于植入2,6周时(P <0.05),对照组植入6周时的最大压缩载荷高于植入2,4周时(P <0.05);(4)结果表明,等离子体电解氧化涂层钛棒植入早期的骨整合能力优于普通钛棒。
BACKGROUND:Numerous quantitatively based studies measuring the accuracy of 3D shoulder ultrasound (US) for the diagnosis of rotator cuff tears remain inconclusive. In order to determine how effective 3D shoulder US is for detecting rotator cuff tears, a meta-analysis was performed systematically.METHODS:Six electronic databases, PubMed/Medline, Embase, Cochrane Library, CNKI, VIP data, and Wanfang data, were utilized to retrieve articles praising the diagnostic value of 3D shoulder US for use in detecting rotator cuff tears. After screening and diluting out the articles that met inclusion criteria to be used for statistical analysis, the pooled evaluation indexes including sensitivity, specificity, and diagnostic odds ratio (DOR) as well as the summary receiver operating characteristic curve (SROC) were calculated utilizing Meta-Disc v.1.4.RESULTS:Screening determined that out of 4220, 7 studies involving a total of 282 patients were deemed viable for inclusion in the meta-analysis. The results of the analysis showed that the sensitivity and specificity were at 94% and 83%, respectively, with a DOR of 60.06, Q* index of 0.9058 and the area under SROC of 0.9609. Additionally, a satisfactory accuracy of 3D shoulder US was observed in detecting full- and partial-thickness rotator cuff tears.CONCLUSION:This meta-analysis suggests that 3D shoulder US is very effective and highly accurate to detect full-thickness rotator cuff tears, but may lack accuracy in the diagnosis of partial tears.
Autogenous tissue grafting remains the gold standard in the treatment of critical sized bone and certain cartilage defects, while the translation of tissue engineered osteogenesis or chondrogenesis from the lab bench into clinical practice, utilizing natural or synthetic biomimetic devices, remains challenging. One of the crucial underestimated reasons for non-translatability could be the imprecision and inconsistency of generated gene expression profiles, utilizing improperly optimized and standardized quantitative gene assays. Utilizing GeNorm for downstream qRT-PCR applications, the stability of reference genes in relation to optimal cDNA amounts was assessed on human bone marrow-derived mesenchymal and adipose-derived stem cells neat and made to differentiate into chondrocytes including normal human derived chondrocytes and muscle tissue from rats. Results showed that reference genes can vary substantially across separately and/or combined cell lines and/or tissue types including treatment parameters. The recommendations to all bone and cartilage tissue engineers utilizing qRT-PCR is not to assume that reference gene stability and quantity remain conserved across cell lines or tissue types but to always determine, for each new experiment, the stability and normalization quantity of reference genes anew.
The aim of the present study was to determine the correlation between bone volume density (BV/TV) around a titanium implant determined by micro-computed tomography (micro-CT) and bone area density (BA/TA) measurements obtained using histomorphometry. An intramedullary rat femur implant model was evaluated to compare raw titanium implants with plasma electrolytic oxidation (PEO)-coated titanium implants. Titanium and PEO-treated titanium pins were inserted into rat femurs under general anesthesia. The animals were sacrificed and femurs harvested at 0, 2, 4 and 6 weeks, and subsequently, histomorphometry and micro-CT were performed. BV/TV and BA/TA values were strongly and positively correlated at all time points and locations (with all correlation coefficients being > 0.8 and with P < 0.001). BV/TV and BA/TA were significantly higher proximal to the growth plate than distal to the growth plate, with estimated differences of 14.10% (P < 0.001) and 11.95% (P < 0.001), respectively. BV/TV and BA/TA were significantly higher on the PEO-coated surface than on the raw titanium surface, with estimated differences of 3.20% (P = 0.044) and 4.10% (P = 0.018), respectively. Therefore, quantitative micro-CT analysis of BV/TV is correlated with BA/TA determined by histomorphometry when artifacts around titanium implants are minimized by a region of interest modification.
PURPOSE:Our aim was to define the effect of multiple biomarkers of osteolysis or bone remodelling in the early detection of aseptic loosening (AL) of total hip arthroplasty (THA).METHOD:One hundred subjects were recruited, including 31 candidates for revision THA (Late AL group), 15 patients who had undergone THA and had clinical and radiographic evidence of AL (early AL group), 19 patients with no sign of AL (stable group), and 40 healthy volunteers. Plasma levels of osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB ligand (RANKL), cross-linked N-terminal telopeptide (NTX), procollagen I C-terminal extension peptide (PICP), tumour necrosis factor-alpha (TNF-α), and interleukin (IL)-1β1 were measured using an immunoenzymatic method. The outcomes of biomarkers were analysed separately and synthetically using Revman software.RESULTS:The plasma level of OPG, RANKL, NTX, TNF-α, and IL-1β declined from late AL, early AL, stable to the healthy group, while the level of PICP inclined reversely. There was a significant difference in synthetic analysis of six biomarkers between the AL group and the stable group, and between the stable group and the healthy group (both p = 0.02). Heterogeneity of six biomarkers in either comparison was extremely low (both I(2) =0). Patients who had cemented implants had significantly higher levels of TNF-α than patients with cementless varieties (p = 0.042).CONCLUSION:There was significant change in the plasma level of multiple biomarkers in patients with prosthetic AL of THA, especially in the cemented arthroplasties and in patients without traditional clinical or radiographic evidence of AL.