Prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections.

Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue. Its high recurrence rate and impaired restoration of bone deficiencies are major challenges in treatment. Microbes have evolved numerous mechanisms to effectively evade host intrinsic and adaptive immune attacks to persistently localize in the host, such as drug-resistant bacteria, biofilms, persister cells, intracellular bacteria, and small colony variants (SCVs). Moreover, microbial-mediated dysregulation of the bone immune microenvironment impedes the bone regeneration process, leading to impaired bone defect repair. Despite advances in surgical strategies and drug applications for the treatment of bone infections within the last decade, challenges remain in clinical management. The development and application of tissue engineering materials have provided new strategies for the treatment of bone infections, but a comprehensive review of their research progress is lacking. This review discusses the critical pathogenic mechanisms of microbes in the skeletal system and their immunomodulatory effects on bone regeneration, and highlights the prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections. It will inform the development and translation of antimicrobial and bone repair tissue engineering materials for the management of bone infections.

3D Printed Multifunctional Biomimetic Bone Scaffold Combined with TP-Mg Nanoparticles for the Infectious Bone Defects Repair.

Infected bone defects are one of the most challenging problems in the treatment of bone defects due to the high antibiotic failure rate and the lack of ideal bone grafts. In this paper, inspired by clinical bone cement filling treatment, α-c phosphate (α-TCP) with self-curing properties is composited with ß-tricalcium phosphate (ß-TCP) and constructed a bionic cancellous bone scaffolding system α/ß-tricalcium phosphate (α/ß-TCP) by low-temperature 3D printing, and gelatin is preserved inside the scaffolds as an organic phase, and later loaded with a metal-polyphenol network structure of tea polyphenol-magnesium (TP-Mg) nanoparticles. The scaffolds mimic the structure and components of cancellous bone with high mechanical strength (>100 MPa) based on α-TCP self-curing properties through low-temperature 3D printing. Meanwhile, the scaffolds loaded with TP-Mg exhibit significant inhibition of Staphylococcus aureus (S.aureus) and promote the transition of macrophages from M1 pro-inflammatory to M2 anti-inflammatory phenotype. In addition, the composite scaffold also exhibits excellent bone-enhancing effects based on the synergistic effect of Mg2+ and Ca2+. In this study, a multifunctional ceramic scaffold (α/ß-TCP@TP-Mg) that integrates anti-inflammatory, antibacterial, and osteoinduction is constructed, which promotes late bone regenerative healing while modulating the early microenvironment of infected bone defects, has a promising application in the treatment of infected bone defects.

Antibody-antibiotic conjugate targeted therapy for orthopedic implant-associated intracellular S. aureus infections.

INTRODUCTION: Treating orthopedic implant-associated infections, especially those caused by Staphylococcus aureus (S. aureus), remains a significant challenge. S. aureus has the ability to invade host cells, enabling it to evade both antibiotics and immune responses during infection, which may result in clinical treatment failures. Therefore, it is critical to identify the host cell type of implant-associated intracellular S. aureus infections and to develop a strategy for highly targeted delivery of antibiotics to the host cells. OBJECTIVES: Introduced an antibody-antibiotic conjugate (AAC) for the targeted elimination of intracellular S. aureus. METHODS: The AAC comprises of a human monoclonal antibody (M0662) directly recognizes the surface antigen of S. aureus, Staphylococcus protein A, which is conjugated with vancomycin through cathepsin-sensitive linkers that are cleavable in the proteolytic environment of the intracellular phagolysosome. AAC, vancomycin and vancomycin combined with AAC were used in vitro intracellular infection and mice implant infection models. We then tested the effect of AAC in vivo and in vivo by fluorescence imaging, in vivo imaging, bacterial quantitative analysis and bacterial biofilm imaging. RESULTS: In vitro, it was observed that AAC captured extracellular S. aureus and co-entered the cells, and subsequently released vancomycin to induce rapid elimination of intracellular S. aureus. In the implant infection model, AAC significantly improved the bactericidal effect of vancomycin. Scanning electron microscopy showed that the application of AAC effectively blocked the formation of bacterial biofilm. Further histochemical and micro-CT analysis showed AAC significantly reduced the level of bone marrow density (BMD) and bone volume fraction (BV/TV) reduction caused by bacterial infection in the distal femur of mice compared to vancomycin treatment alone. CONCLUSIONS: The application of AAC in an implant infection model showed that it significantly improved the bactericidal effects of vancomycin and effectively blocked the formation of bacterial biofilms, without apparent toxicity to the host.

Evaluation and Application of Silk Fibroin Based Biomaterials to Promote Cartilage Regeneration in Osteoarthritis Therapy.

Osteoarthritis (OA) is a common joint disease characterized by cartilage damage and degeneration. Traditional treatments such as NSAIDs and joint replacement surgery only relieve pain and do not achieve complete cartilage regeneration. Silk fibroin (SF) biomaterials are novel materials that have been widely studied and applied to cartilage regeneration. By mimicking the fibrous structure and biological activity of collagen, SF biomaterials can promote the proliferation and differentiation of chondrocytes and contribute to the formation of new cartilage tissue. In addition, SF biomaterials have good biocompatibility and biodegradability and can be gradually absorbed and metabolized by the human body. Studies in recent years have shown that SF biomaterials have great potential in treating OA and show good clinical efficacy. Therefore, SF biomaterials are expected to be an effective treatment option for promoting cartilage regeneration and repair in patients with OA. This article provides an overview of the biological characteristics of SF, its role in bone and cartilage injuries, and its prospects in clinical applications to provide new perspectives and references for the field of bone and cartilage repair.

rFSAV promotes Staphylococcus aureus-infected bone defect healing via IL-13- mediated M2 macrophage polarization.

Staphylococcus aureus (S. aureus) contamination commonly occurs in orthopedic internal fixation operations, leading to a delayed healing of the defected bone tissue. However, antibiotic treatments are ineffective in dealing with S. aureus bone infections due to the rise in multiple antimicrobial resistances. Here, we reported the protective effects of a recombinant five-antigen S. aureus vaccine (rFSAV) in an S. aureus infected bone defect model. In this study, we found the number of M2 macrophages markedly increased in the defect site and played a critical role in the healing of defected bone mediated by rFSAV. Mechanistically, rFSAV mediated increased level of IL-13 in bone defect site predominant M2 macrophage polarization. In summary, our study reveals a key role of M2 macrophage polarization in the bone regeneration process in S. aureus infection induced bone defect, which provide a promising application of rFSAV for the treatment of bone infection for orthopedic applications.

The miR-21-5p enriched in the apoptotic bodies of M2 macrophage-derived extracellular vesicles alleviates osteoarthritis by changing macrophage phenotype.

Macrophages (Mφs) play a crucial role in the pathological progression of osteoarthritis (OA) by regulating inflammation and tissue repair. Decreasing pro-inflammatory M1-Mφs and increasing anti-inflammatory M2-Mφs can alleviate OA-related inflammation and promote cartilage repair. Apoptosis is a natural process associated with tissue repair. A large number of apoptotic bodies (ABs), a type of extracellular vesicle, are produced during apoptosis, and this is associated with a reduction in inflammation. However, the functions of apoptotic bodies remain largely unknown. In this study, we investigated the role of M2-Mφs-derived apoptotic bodies (M2-ABs) in regulating the M1/M2 balance of macrophages in a mouse model of OA. Our data show that M2-ABs can be targeted for uptake by M1-Mφs, and this reprograms M1-to-M2 phenotypes within 24 h. The M2-ABs significantly ameliorated the severity of OA, alleviated the M1-mediated pro-inflammatory environment, and inhibited chondrocyte apoptosis in mice. RNA-seq revealed that M2-ABs were enriched with miR-21-5p, a microRNA that is negatively correlated with articular cartilage degeneration. Inhibiting the function of miR-21-5p in M1-Mφs significantly reduced M2-ABs-guided M1-to-M2 reprogramming following in vitro cell transfection. Together, these results suggest that M2-derived apoptotic bodies can prevent articular cartilage damage and improve gait abnormalities in OA mice by reversing the inflammatory response caused by M1 macrophages. The mechanism underlying these findings may be related to miR-21-5p-regulated inhibition of inflammatory factors. The application of M2-ABs may represent a novel cell therapy, and could provide a valuable strategy for the treatment of OA and/or chronic inflammation.

Joint fluid interleukin-6 combined with the neutral polymorphonuclear leukocyte ratio (PMN%) as a diagnostic index for chronic periprosthesis infection after arthroplasty.

BACKGROUND: The diagnosis of periprosthetic joint infection (PJI) remains a challenge in clinical practice. Many novel serum and joint fluid biomarkers have important implications for the diagnosis of PJI. The presented study evaluated the value of joint fluid interleukin-6 (IL-6) combined with the neutral polymorphonuclear leukocyte (PMN%) ratio for chronic PJI diagnosis after arthroplasty. MATERIALS AND METHODS: Sixty patients with chronic PJI or aseptic failure who underwent hip or knee revision from January 2018 to January 2020 in our department were included in this retrospective study. According to the 2013 MSIS diagnostic criteria, the 60 patients were divided into a PJI group and a non-PJI group (30 patients per group). We collected the joint fluid before surgery and determined the level of IL-6 and the PMN% by ELISA, and the differences between the two groups were compared. The diagnostic efficacy of joint fluid IL-6 combined with PMN% in chronic PJI was analyzed using a receiver operating characteristic curve (ROC curve). RESULTS: The diagnosis of PJI using joint fluid IL-6 combined with PMN% presented an area under the curve of 0.983, which was more accurate than the areas under the curve for diagnosis using IL-6 and PMN% individually (0.901 and 0.914, respectively). The optimal threshold values for IL-6 and PMN% were 662.50 pg/ml and 51.09%, respectively. Their sensitivity and specificity were 96.67% and 93.33%, respectively. The accuracy of the diagnosis of PJI was 95.00%. CONCLUSIONS: Joint fluid IL-6 combined with PMN% can be used as an auxiliary method to detect chronic infection around the prosthesis after hip/knee arthroplasty. LEVEL OF EVIDENCE: Patients who underwent hip/knee revision at the First Hospital of Chongqing Medical University for periprosthetic infection or aseptic failure of the prosthesis after hip/knee arthroplasty from January 2018 to January 2020 were included. Trial registration This study was approved by the ethics committee of the First Hospital of Chongqing Medical University on September 26, 2018 (local ethics committee number: 20187101) and registered with the China Clinical Trials Registry (registration number: ChiCTR1800020440) with an approval date of December 29, 2018.

Detection of inguinal lymph nodes is promising for the diagnosis of periprosthetic joint infection.

Background: Localized inguinal lymphadenopathy often represents lower extremity pathogen infection, while normalized lymphadenopathy is associated with infection regression. We hypothesized that inguinal lymph nodes (LNs) were enlarged in Periprosthetic Joint Infection (PJI) patients and that normalized inguinal LNs would be a promising way to determine the timing of reimplantation. Methods: We prospectively enrolled 176 patients undergoing primary and revision hip or knee arthroplasty. All patients underwent ultrasound examination of inguinal LNs preoperatively. The diagnostic value of inguinal LNs in PJI was evaluated by the receiver operating characteristic (ROC) curve. Results: The median level of inguinal LNs was 26mm in the revision for PJI group compared with 12 mm in the aseptic revision group (p< 0.0001). The size of the inguinal LNs well distinguishes PJI from aseptic failure (AUC= 0.978) compare with ESR (AUC= 0.707) and CRP (AUC= 0.760). A size of 19mm was determined as the optimal threshold value of the inguinal LNs for the diagnosis of PJI, with a sensitivity of 92% and specificity of 96%. Conclusion: Ultrasonic analysis of inguinal LNs is a valuable piece of evidence for the diagnosis of PJI and evaluation of persistent infection.

Preparation and Characterization of Biomimetic Functional Scaffold with Gradient Structure for Osteochondral Defect Repair.

Osteochondral (OC) defects cannot adequately repair themselves due to their sophisticated layered structure and lack of blood supply in cartilage. Although therapeutic interventions are reaching an advanced stage, current clinical therapies to repair defects are in their infancy. Among the possible therapies, OC tissue engineering has shown considerable promise, and multiple approaches utilizing scaffolds, cells, and bioactive factors have been pursued. The most recent trend in OC tissue engineering has been to design gradient scaffolds using different materials and construction strategies (such as bi-layered, multi-layered, and continuous gradient structures) to mimic the physiological and mechanical properties of OC tissues while further enabling OC repair. This review focuses specifically on design and construction strategies for gradient scaffolds and their role in the successful engineering of OC tissues. The current dilemmas in the field of OC defect repair and the efforts of tissue engineering to address these challenges were reviewed. In addition, the advantages and limitations of the typical fabrication techniques for gradient scaffolds were discussed, with examples of recent studies summarizing the future prospects for integrated gradient scaffold construction. This updated and enlightening review could provide insights into our current understanding of gradient scaffolds in OC tissue engineering.

The Ratio of IL-6 to IL-4 in Synovial Fluid of Knee or Hip Performances a Noteworthy Diagnostic Value in Prosthetic Joint Infection.

The diagnosis of prosthetic joint infection (PJI) is still a challenge, the ratio of interleukin-6 (IL-6) to IL-4 in the joint fluid of knee or hip was used to analyze whether the diagnostic accuracy of PJI can be improved. Between January 2017 and May 2022, 180 patients who developed pain after revision total hip or knee arthroplasty were enrolled retrospectively. 92 patients of PJI and 88 of aseptic failure were included. PJI was as defined by the Musculoskeletal Infection Society (MSIS). The content of IL-6 and IL-4 in synovial fluid of knee or hip were measured, and the areas under the receiver operating characteristic curve (ROC) and IL-6/IL-4 curve were analyzed to obtain a better diagnostic effect. The area under the curve of IL-6/IL-4 in synovial fluid of knee or hip was 0.9623, which was more accurate than ESR 0.5994 and C-reactive protein 0.6720. The optimal threshold of IL-6/IL-4 ratio was 382.10. Its sensitivity and specificity were 81.32% and 98.86%, respectively. The positive predictive value for the diagnosis of PJI was 98.91%. This study showed that the level of IL-6/IL-4 in synovial fluid of knee or hip could further improve the diagnostic accuracy for PJI.

River habitat assessment and restoration in high dam flood discharge systems with total dissolved gas supersaturation.

The success of river habitat restoration relies on accurate assessment proxies. However, determining how to quantitatively assess the impact of multiple stressors during flood discharge from high dams in riverine ecosystems and where and how to implement more reliable recovery interventions remain challenges. Here, we developed a bottom-up mechanistic framework for assessing the effects of total dissolved gas supersaturation (TDGS) and hydrodynamics on fish habitat quality and applied it to the downstream river reach of the Xiangjiaba Dam in Southwest China. The results showed that the available habitat area of river sturgeon was the smallest, while Chinese sucker had the largest available habitat area among the three target species under all discharge scenarios. Although the TDGS levels were evenly mixed laterally, the habitat suitability index indicated that the suitable habitats were primarily within both sides of the river reach under all scenarios, which is contrary to findings based on the traditional TDGS risk assessment model. The traditional TDGS risk assessment model overestimates the impact of dams on habitats. This divergence reflected the sensitivity of the habitat assessment to fish habitat preferences, fish tolerance to TDGS and the biological response of fish under TDGS. Additionally, the priority areas for restoration can be identified by habitat suitability index with lower values. We simulated twenty-four schemes and found that interventions such as stone groups, ecological spur dike, water-retaining weir and river dredging can enhance habitat suitability for fish species under multiple stressors, providing novel insights into where and how to mitigate the impact of TDGS. Our findings offer a transferable framework for the quantitative evaluation of fish habitat and implementation of restoration management during dam flood discharge periods, thus providing a new perspective for biodiversity conservation and habitat restoration in dam-regulated rivers with TDGS around the world.

Synovial Fluid Interleukin Levels Cannot Distinguish between Prosthetic Joint Infection and Active Rheumatoid Arthritis after Hip or Knee Arthroplasty.

Inflammatory arthritis affects the level of synovial inflammatory factors, which makes it more difficult to diagnose prosthetic joint infection (PJI) patients with inflammatory arthritis. The aim of this study was to analyze synovial interleukin levels to distinguish between PJI and active rheumatoid arthritis (RA) after a hip or knee arthroplasty. From September 2019 to September 2021, we prospectively enrolled patients with joint pain after arthroplasty due to aseptic prosthesis loosening (n = 39), acute RA (n = 26), and PJI (n = 37). Synovial fluid from the affected joint is obtained and tested with a standard enzyme-linked immunosorbent assay. Receiver operating characteristic curve (ROC) was analyzed for each biomarker. Interleukin (IL)-1ß, IL-6, and IL-8 showed promising value in differentiating of aseptic loosening from PJI, with areas under the curves (AUCs) of 0.9590, 0.9506, and 0.9616, respectively. Synovial IL-1ß, IL-6, and IL-8 showed limited value in distinguishing between PJI and acute episodes of RA after arthroplasty, with AUCs of 0.7507, 0.7069, and 0.7034, respectively. Interleukins showed satisfactory efficacy in differentiating aseptic loosening from PJI. However, when pain after arthroplasty results from an acute episode of RA, current synovial interleukin levels do not accurately rule out the presence of PJI.

Changes in Thromboelastography to Predict Ecchymosis After Knee Arthroplasty: A Promising Guide for the Use of Anticoagulants.

Background: Ecchymosis is one of the worrisome complications after total knee arthroplasty (TKA) and interferes with functional rehabilitation. Current clinical guidelines do not provide individualized approaches for patients with ecchymoses. Methods: In this study, we used thromboelastography (TEG) to determine the coagulation state after TKA and to then explore markers that predict the occurrence of ecchymosis events after TKA. In our cohort, patients were divided into ecchymosis (n = 55) and non-ecchymosis (n = 137) groups according to whether ecchymosis events occurred after TKA. Rivaroxaban 10 mg/d was taken orally for thromboprophylaxis after surgery. All patients completed TEG testing. Correlation analysis was used to determine the risk factors for ecchymosis after TKA, and receiver operating characteristic (ROC) curves for variables with significant correlation were plotted. Results: In all, 55 of the 192 patients (28.65%) developed ecchymosis surrounding the surgical site. Multivariate analysis showed that hidden blood loss (OR = 1.003 and p = 0.005) and changes in the coagulation index (ΔCI) values (OR = 0.351 and p = 0.001) were risk factors for ecchymosis after TKA. Using the Youden index, 0.1805 was determined as the optimal threshold value of ΔCI for predicting the occurrence of ecchymosis, with a sensitivity of 74.55% and specificity of 72.99%. ΔCI is a promising marker as an alarm for the occurrence of ecchymosis after TKA. Trial Registration: The study was registered in the Chinese Clinical Trial Registry (ChiCTR1800017245). Registered name: The role of thrombelastography in monitoring the changes of coagulation function during perioperative period of arthroplasty. Registered 19 July 2018. http://www.chictr.org.cn/showproj.aspx?proj=29220.

Combination of Synovial Fluid IL-4 and Polymorphonuclear Cell Percentage Improves the Diagnostic Accuracy of Chronic Periprosthetic Joint Infection.

Background: Synovial fluid biomarkers have been found to improve the diagnosis of chronic periprosthetic joint infection (PJI); however, no "gold standard" exists yet. Interleukin-4 (IL-4) and polymorphonuclear cell (neutrophil) count in the synovial fluid are crucial in mediating local inflammation during bacterial infections and could be valuable biomarkers for PJI. Methods: This prospective study was conducted to investigate the diagnostic potential of synovial fluid IL-4 (SF-IL4) and polymorphonuclear cell percentage (SF-PMN%) for chronic PJI. A total of 110 patients who underwent revision arthroplasty between January 2019 and October 2020 were enrolled, and 11 patients were excluded. Of 99 patients, 43 were classified as having PJI and 56 as having aseptic failures according to the 2013 Musculoskeletal Infections Society criteria. In all patients, SF-IL4, SF-PMN%, serum C-reactive protein (CRP), and serum erythrocyte sedimentation rate (ESR) were quantified preoperatively. The diagnostic value for each biomarker was analyzed, and optimal cutoff values were calculated. Results: The patient demographics did not significantly vary. The area under the curve of SF-IL4 and SF-PMN% was 0.97 and 0.89, respectively, higher than that for serum ESR (0.72) and serum CRP (0.83). The combination of SF-IL4 and SF-PMN% provided higher specificity (97.0%) and accuracy (96.0%) when the cut-off values were 1.7 pg/mL and 75%, respectively. Conclusion: SF-IL4 is a valuable biomarker for chronic PJI detection, and the combination of SF-IL4 and SF-PMN% improved the diagnostic value of chronic PJI, and further studies are needed until its clinical application.

The typically developing pediatric foot - The data of the 1744 children in China.

BACKGROUND: The medial longitudinal arch (MLA) improves with age in childhood. However, it still causes parents to worry that children have flat feet. Due to the lack of a standard to quantitatively assess the arch development in kids at certain age, the pediatricians judge the flat feet by experience, causing many cases to be overtreated. The aim of this study was to plot the distribution of MLA parameters in children. METHODS: Children without lower limb deformity and lower limb pain were recruited from 12 primary schools and kindergartens in Chongqing province-level city. Foot length (FL) and navicular height (NH) was measured manually, arch index (AI) and arch volume (AV) were measured with the Foot Plantar Scanner. Each parameter was measured in both weight-bearing and non-weight-bearing positions. Significant differences were also compared between the measurements of consecutive years. RESULTS: This study was the first to use a three-dimensional laser surface scanner to measure the MLA parameters of children aged 3-12 years in China. 1744 children (871 girls, 873 boys) participated in this study. FL, NH, AI and AV varied significantly with age in both the weight-bearing and non-weight-bearing positions. These parameters have significant differences between the weighted and non-weighted positions (p < 0.05). CONCLUSIONS: The age distribution characteristics of these parameters indicated that the MLA improves with age. The establishment of a developmental scale for the children's MLA is necessary.

Serum and Synovial Biomarkers for Distinguishing Between Chronic Periprosthetic Joint Infections and Rheumatoid Arthritis: A Prospective Cohort Study.

BACKGROUND: Inflammatory responses in patients with active rheumatoid arthritis (RA) may lead to the current serum and synovial fluid biomarkers that misidentify chronic periprosthetic joint infection (PJI). We sought to investigate the expression of serum and synovial biomarkers in patients with active RA and to calculate thresholds for valuable biomarkers that distinguish between chronic PJI and active RA. METHODS: This prospective study was initiated to enroll 70 patients undergoing revision arthroplasty from January 2019 to January 2021, and 30 patients with active RA cumulative knee from August 2020 to March 2021. The Musculoskeletal Infection Society definition of PJI was utilized for the classification of cases as aseptic or infected. Serum d-dimer, erythrocyte sedimentation rate, C-reactive protein, and interleukin-6 (IL-6), as well as synovial IL-6, percentage of polymorphonuclear neutrophils, and CD64 index level were measured preoperatively. RESULTS: An increase in biomarker concentrations were observed in group C (active RA). Synovial fluid CD64 index exhibited good discriminatory power between group B (chronic PJI) and group C with an area under curve of 0.930. For the diagnosis of chronic PJI in the presence of active RA, the optimal threshold value of synovial CD64 index was 0.87, with a sensitivity of 82.86% and a specificity of 93.33%. CONCLUSION: Current serum biomarkers (erythrocyte sedimentation rate, C-reactive protein, IL-6, and d-dimer) did not apply to the diagnosis of suspected PJI with active RA. Fortunately, satisfactory results can be achieved by adjusting the threshold of synovial fluid biomarkers.

Combined serum and synovial C-reactive protein tests: a valuable adjunct to the diagnosis of chronic prosthetic joint infection.

BACKGROUND: Diagnosis of periprosthetic joint infection (PJI), especially chronic PJI, is very confusing and challenging. The value of C-reactive protein (CRP) in infectious diseases has been recognized, but the diagnostic value of CRP in chronic PJI is unknown. Our aim was to investigate the diagnostic value of synovial CRP in chronic PJI and to explore the role of combined serum and synovial CRP in distinguishing chronic PJI from aseptic failure after knee and hip arthroplasties. METHODS: We prospectively enrolled patients scheduled to have a revision surgery for chronic PJI or aseptic loosening from January 2019 to December 2020, in which synovial CRP was additionally measured along with routine preoperative diagnostic serum ((ESR, CRP) and synovial (PMN%) biomarkers. The receiver operating characteristic (ROC) curves and area under the curve (AUC) were analyzed for each biomarker to determine diagnostic efficacy. RESULTS: There were no statistically significant differences between the infection (n = 39) and aseptic (n = 58) groups, including 61 hips and 36 knees. The synovial CRP levels were significantly higher in the infection group than in the aseptic group (median: 9.93 mg/l vs 3.58 mg/l; p < .001). The optimal cut-off value for detecting chronic PJI of Synovial fluid (SF) CRP was of 7.26 mg/l with a sensitivity of 84.62%, a specificity of 93.10%. The combined model I (Serum CRP > 10.2 mg/l OR SF CRP > 7.26 mg/l) had a negative predictive value (NPV) of 96.67%, and a sensitivity of 97.44%. The combined model II (Serum CRP > 10.2 mg/l AND Synovial CRP > 7.26 mg/l) led to a specificity of 1, and a positive predictive value (PPV) of 1. CONCLUSIONS: The present study demonstrated that the combination of serum and synovial CRP can be used as an adjunct to the diagnosis of chronic PJI.

Astragalus polysaccharide attenuates LPS-related inflammatory osteolysis by suppressing osteoclastogenesis by reducing the MAPK signalling pathway.

Bacterial products can stimulate inflammatory reaction and activate immune cells to enhance the production of inflammatory cytokines, and finally promote osteoclasts recruitment and activity, leading to bone destruction. Unfortunately, effective preventive and treatment measures for inflammatory osteolysis are limited and usually confuse the orthopedist. Astragalus polysaccharide (APS), the main extractive of Astragali Radix, has been widely used for treating inflammatory diseases. In the current study, in vitro and in vivo experimental results demonstrated that APS notably inhibited osteoclast formation and differentiation dose-dependently. Moreover, we found that APS down-regulated RANKL-related osteoclastogenesis and levels of osteoclast marker genes, such as NFATC1, TRAP, c-FOS and cathepsin K. Further underlying mechanism investigation revealed that APS attenuated activity of MAPK signalling pathways (eg ERK, JNK and p38) and ROS production induced by RANKL. Additionally, APS was also found to suppress LPS-related inflammatory osteolysis by decreasing inflammatory factors' production in vivo. Overall, our findings demonstrate that APS effectively down-regulates inflammatory osteolysis due to osteoclast differentiation and has the potential to become an effective treatment of the disorders associated with osteoclast.

Linking bait and feeding opportunities to fish foraging habitat for the assessment of environmental flows and river restoration.

The survival of aquatic biota in different life history stages depends on food availability, water quantity and specific hydrological conditions, and is particularly susceptible in degraded rivers due to the development of hydropower or are sensitive to climate change. Habitats with limited food availability and restricted feeding opportunities can strongly affect the habitat carrying capacity and fish growth with consequences for spawning. Few environmental flow regime frameworks are available that closely link bait and feeding opportunities to fish foraging habitat. In addition, river restoration has been widely implemented to resolve the conflict between ecological demand and power generation benefits. Nevertheless, whether in-stream structures are still suitable for the joint operation of foraging and spawning habitats remains unclear. In this study, a framework to integrate the requirements of both spawning and foraging habitats into environmental flow regime assessments was proposed by coupling the bait supply, fish spawning and fish feeding opportunities. Here, we used the Batang Reservoir, located in the Tibetan Plateau, as an example to determine the environmental flow regimes. The environmental flow regimes during Periods I, II and III for the conservation of the life history stages of Schizothorax dolichonem were determined, which provided high-quality food and was beneficial for increasing the probability of restoration success. After the implementation of measures, the ecological base flow rate decreased from 171.80 m3/s, 206.00 m3/s and 257.70 m3/s to 138.00 m3/s, 206.00 m3/s and 206.00 m3/s in Periods I, II and III, respectively. We concluded that traditional river restoration with the use of in-stream structures is still suitable for the joint operation of spawning and foraging habitats, but the design selection and placement of in-stream structures should be preoptimized. The framework proposed will help managers evaluate habitat conservation to protect degraded rivers or help develop strategies to build resilience to climate change.

Synovial fluid IL-1ß appears useful for the diagnosis of chronic periprosthetic joint infection.

PURPOSE: The purpose of this study was to investigate the role of synovial fluid interleukin (IL)-1ß in diagnosing chronic periprosthetic joint infection (PJI) and to identify the optimal threshold of synovial fluid IL-1ß for differentiating chronic PJI from aseptic failure after knee and hip arthroplasties. METHODS: Between January 2019 and December 2019, we prospectively included patients scheduled to have a revision surgery for chronic PJI or aseptic failure after total joint arthroplasty. Then, synovial IL-1ß was additionally measured along with routine preoperative diagnostic serum and synovial biomarkers. The receiver operating characteristic (ROC) curves and area under the curve (AUC) were analyzed for each biomarker to determine diagnostic efficacy. RESULTS: Of the 93 patients included, their demographic data were not found to be statistically significant. The median synovial IL-1ß levels were significantly higher in the chronic PJI group than in the aseptic group (894.73 pg/mL vs. 34.49 pg/mL, P<0.01). The AUC for synovial fluid IL-1ß was 0.991, which was higher than serum ESR (0.627) and CRP (0.712). The optimal threshold value for detecting chronic PJI of synovial IL-1ß was 312.7 pg/mL, with a sensitivity of 97.3% and a specificity of 94.64%. And the combined measurement of synovial fluid IL-1ß and synovial fluid PMN% can led to a specificity of 1, and a negative predictive value (NPV) of 1. CONCLUSIONS: The present study demonstrated that synovial fluid IL-1ß is a valuable biomarker for detection of chronic PJI. The combination of synovial fluid IL-1ß and PMN% led to an improvement in specificity compared with evaluation of each single index. TRIAL REGISTRATION: This study was prospectively registered on the Chinese Clinical Trial Registry (a non-profit organization, established according to both the WHO International Clinical Trials Register Platform Standard and Ottawa Group Standard), and the registering number was ChiCTR1800020440 . Registered on December 29, 2018.