Preoperative transthoracic echocardiography does not lead to decreased postoperative mortality but with increased time to surgery and length of stay in Chinese geriatric hip fracture patients.

PURPOSE: The present study aimed to investigate the influence of preoperative TTE on postoperative short-term mortality, surgery delay, as well as other economic and clinical outcomes in Chinese geriatric hip fracture patients. METHODS: This retrospective, matched-cohort study enrolled geriatric hip fracture patients (≥ 60 years) who underwent surgical interventions at our center between 2015 and 2020. The primary exposure was inpatient preoperative TTE. Demographic and clinical data that were reported as risk factors for postoperative mortality were retrieved from the medical data center as the covariates. The primary clinical outcomes were all-cause mortality at 30 days, 90 days, 180 days, and 1 year. Time from hospital presentation to surgery, length of stay (LOS), inpatient cost, frequency of cardiology consultation and coronary angiography (CAG) were also assessed. The propensity score matching (PSM) was performed in a ratio of 1:1. RESULTS: 447 patients were identified and 216 of them received a preoperative TTE (48.3%). After successfully matching 390 patients (87.2%), patients receiving TTE showed significantly higher 30-day mortality (6.6% vs 2.0%, P = 0.044). But no significant difference was found in 90-day, 180-day, and 365-day mortality as well as the 1-year accumulated survival rate. Receipt of TTE was also associated with significant increases in LOS (13.6 days vs 11.4 days, P = 0.017), waiting time for surgery (5.9 days vs 4.3 days, P < 0.001), and lower proportion of receiving surgery within 48 h (7.2% vs. 26.2%, P < 0.001). According to the multivariable logistic analysis, only ejection fraction (30 days, 90 days), aorta diameter (30 days, 90 days, 180 days, 365 days), left ventricular posterior wall diameter (90 days, 180 days, 365 days), aortic valve velocity (90 days) and mitral valve A-peak (90 days, 180 days) were association with postoperative mortality among the 17 parameters in the TTE reports. Besides, TTE has no influence on the frequency of preoperative cardiology consultation. CONCLUSION: Preoperative TTE does not lead to decreased postoperative mortality but with increased time to surgery and length of stay in Chinese geriatric hip fracture patients. The predictive ability of TTE parameters is limited for postoperative mortality.

Intraoperative intravenous versus periarticular injection of glucocorticoids in improving clinical outcomes after total knee arthroplasty: A prospective, randomized and controlled study.

BACKGROUND: Glucocorticoids have been widely used in perioperative period for postoperative pain relief after total knee arthroplasty (TKA). However, the optimal administration protocols of glucocorticoids remain controversial. This study aims to compare the efficacy of glucocorticoids between intravenous and periarticular injection on clinical outcomes. METHODS: A total of 114 patients were randomly assigned to intravenous (IV) group (n = 57) and periarticular injection (PI) group (n = 57). The IV group received 10 mg dexamethasone intravenously and the PI group received periarticular injection of 10 mg dexamethasone during the procedure. The clinical outcomes were assessed using visual analogue scale (VAS), knee society score (KSS), range of motion (ROM), knee swelling, inflammation markers and complications after TKA. RESULTS: The VAS score during walking at 2nd day postoperatively was lower in the PI group compared with the IV group (2.08 ± 1.45 vs 2.73 ± 1.69, p = .039), and there was no significant difference at the other time points of VAS score in two groups. The inflammation markers, knee swelling, knee ROM and KSS score were not statistically different. Vomiting and other complications occurrence were not significantly different between the two groups. CONCLUSIONS: Intraoperative periarticular injection of glucocorticoids has similar analgesic effect compared to intravenous in the postoperative period following TKA and may be even more effective on the second postoperative day. In addition, periarticular injection of glucocorticoids does not impose an excess risk or complication on patients.

Enhanced Stability of Dimethyl Ether Carbonylation through Pyrazole Tartrate on Tartaric Acid-Complexed Cobalt-Iron-Modified Hydrogen-Type Mordenite.

In this study, pyrazole tartrate (Pya·DL) and tartaric acid (DL) complexed with cobalt-iron bimetallic modified hydrogen-type mordenite (HMOR) were prepared using the ion exchange method. The results demonstrate that the stability of the dimethyl ether (DME) carbonylation reaction to methyl acetate (MA) was significantly improved after the introduction of Pya·DL to HMOR. The Co∙Fe∙DL-Pya·DL-HMOR (0.8) sample exhibited sustainable stability within 400 h DME carbonylation, exhibiting a DME conversion rate of about 70% and MA selectivity of above 99%. Through modification with the DL-complexed cobalt-iron bimetal, the dispersion of cobalt-iron was greatly enhanced, leading to the formation of new metal Lewis acidic sites (LAS) and thus a significant improvement in catalysis activity. Pya·DL effectively eliminated non-framework aluminum in HMOR, enlarged its pore size, and created channels for carbon deposition diffusion, thereby preventing carbon accumulation and pore blockage. Additionally, Pya·DL shielded the Bronsted acid sites (BAS) in the 12 MR channel, effectively suppressing the side reactions of carbon deposition and reducing the formation of hard carbon deposits. These improvements collectively contribute to the enhanced stability of the DME carbonylation reaction.

Nano wear particles and the periprosthetic microenvironment in aseptic loosening induced osteolysis following joint arthroplasty.

Joint arthroplasty is an option for end-stage septic arthritis due to joint infection after effective control of infection. However, complications such as osteolysis and aseptic loosening can arise afterwards due to wear and tear caused by high joint activity after surgery, necessitating joint revision. Some studies on tissue pathology after prosthesis implantation have identified various cell populations involved in the process. However, these studies have often overlooked the complexity of the altered periprosthetic microenvironment, especially the role of nano wear particles in the etiology of osteolysis and aseptic loosening. To address this gap, we propose the concept of the "prosthetic microenvironment". In this perspective, we first summarize the histological changes in the periprosthetic tissue from prosthetic implantation to aseptic loosening, then analyze the cellular components in the periprosthetic microenvironment post prosthetic implantation. We further elucidate the interactions among cells within periprosthetic tissues, and display the impact of wear particles on the disturbed periprosthetic microenvironments. Moreover, we explore the origins of disease states arising from imbalances in the homeostasis of the periprosthetic microenvironment. The aim of this review is to summarize the role of relevant factors in the microenvironment of the periprosthetic tissues, in an attempt to contribute to the development of innovative treatments to manage this common complication of joint replacement surgery.

Bone turnover biomarkers predict one-year all-cause mortality and walking ability in geriatric hip fracture patients.

PURPOSE: To investigate the utility of serum C-terminal cross-linking telopeptides (ß-CTX) and procollagen type I N propeptide (PINP) for predicting one-year mortality and walking ability in Chinese geriatric hip fracture patients who underwent surgical interventions. METHOD: Elderly patients (≥ 60 years) who underwent surgical interventions for unilateral low-energy hip fracture from 2015 to 2020 in our center were included. Demographic data was retrospectively retrieved from the electronic medical database. The PINP and ß-CTX concentrations were measured before the surgery. The patients were divided into two groups according to the outcome of mortality and walking ability after hip surgery, respectively. ß-CTX and PINP were divided into four grades based on quartiles [Quartile(Q)1-4] for further analysis. All the variables with p < 0.1 in univariable analysis were included in a multivariable model. RESULTS: In univariable analysis, the levels of serum ß-CTX (p = 0.007) and PINP (p = 0.025) was associated with one-year mortality, while the association between levels of serum ß-CTX (p = 0.072) or PINP (p = 0.055) with one-year disability was marginally significant. After adjustment for confounders, the relative risk [OR (95 % CI), Q4 v sQ1, p-value] of one-year mortality and one-year disability were 7.28 (2.08-29.78, p = 0.003) and 3.97 (1.44-11.69, p = 0.009) for ß-CTX and 5.87 (1.70-23.80, p = 0.008) and 3.48 (1.30-9.93, p = 0.016) for PINP, respectively. The coefficient of determination, AUC and bias-corrected C-index of predictive models based on previously reported predictors were significantly improved after integrating ß-CTX or PINP. CONCLUSION: Higher serum ß-CTX and PINP are independently associated with an increased risk of one-year mortality and disability in patients with hip fractures. The application of BTMs improves the performance of currently available predictive models.

Three-dimensional morphological study of the proximal femur in Crowe type IV developmental dysplasia of the hip.

BACKGROUND: When performing femoral reconstruction in patients with Crowe type IV developmental dysplasia of the hip (DDH), anatomical deformity presents many technical challenges to orthopedic surgeons. The false acetabulum is suggested to influence load transmission and femoral development. The aim of this study was to describe the morphological features of dysplastic femurs in Crowe type IV DDH and further evaluate the potential effect of the false acetabulum on morphological features and medullary canal of Crowe type IV femurs. METHODS: We analyzed preoperative computed tomography scans from 45 patients with 51 hips (25 hips without false acetabulum in the IVa group and 26 hips with false acetabulum in the IVb group) who were diagnosed with Crowe type IV DDH and 30 normal hips in our hospital between January 2009 and January 2019. Three-dimensional reconstruction was performed using Mimics software, and the coronal femoral plane was determined to evaluate the following parameters: dislocation height, dislocation ratio, height of the femoral head (FH), height of the greater trochanter (GT), GT-FH height discrepancy, height of the isthmus, neck-shaft angle, femoral offset and anteversion of the femoral neck. The mediolateral (ML) width, anterolateral (AP) width and diameter of medullary canal of the proximal femur were measured on the axial sections. Further, canal flare index (CFI), metaphyseal-CFI and diaphyseal-CFI were also calculated. RESULTS: Compared with the normal femurs, the Crowe type IV DDH femurs had a higher femoral head, larger GT-FH height discrepancy, larger femoral neck anteversion, higher isthmus position and smaller femoral offset. Dislocation height and dislocation rate were significantly larger in the IVa DDH group (65.34 ± 9.83 mm vs. 52.24 ± 11.42 mm). Further, the IVb femurs had a significantly lower isthmus position, larger neck-shaft angle and smaller femoral neck anteversion than IVa femurs. The ML, AP canal widths and the diameter of medullary canal in both DDH groups were significantly smaller than the normal group. Dimensional parameters of IVa femurs were also narrower than IVb femurs in most sections, but with no difference at the level of isthmus. According to the CFIs, the variation of proximal medullary canal in IVb femurs was mainly located in the diaphyseal region, while that in IVa femurs was located in the whole proximal femur. CONCLUSIONS: High dislocated femurs are associated with more anteverted femoral neck, smaller femoral offset and narrower medullary canal. Without stimulation of the false acetabulum, IVa DDH femurs were associated with higher dislocation and notably narrower medullary canal, whose variation of medullary canal was located in the whole proximal femur.

Rapid preoperative predicting tools for 1-year mortality and walking ability of Asian elderly femoral neck fracture patients who planned for hip arthroplasty.

BACKGROUND: Femoral neck fractures in elderly patients typically warrant operative treatment and are related to high risks of mortality and morbidity. As early hip arthroplasties for elderly femoral neck fractures are widely accepted, rapid predicting models that allowed quantitative and individualized prognosis assessments are strongly needed as references for orthopedic surgeons during preoperative conversations. METHODS: Data of patients aged ≥ 65 years old who underwent primary unilateral hemiarthroplasty or total hip arthroplasty due to femoral neck fracture between January 1st, 2012 and June 30th, 2019 in our center were collected. Candidate variables included demographic data, comorbidities, and routine preoperative screening tests. The main outcomes included 1-year mortality and free walking rate after hip arthroplasty. Patients were randomly divided into derivation and validation groups in the ratio of three to one. Nomograms were developed based on multivariable logistic regressions of derivation group via R language. One thousand bootstraps were used for internal validation. Those models were further tested in the validation group for external validation. RESULTS: The final analysis was performed on 702 patients after exclusion and follow-up. All-cause 1-year mortality of the entire data set was 23.4%, while the free walking rate was 57.3%. Preoperative walking ability showed the biggest impact on predicting 1-year mortality and walking ability. Static nomograms were created from the final multivariable models, which allowed simplified graphical computations for the risks of 1-year mortality and walking ability in a certain patient. The bias-corrected C index of those nomograms for predicting 1-year mortality in the derivation group and the validation group were 0.789 and 0.768, while they were 0.807 and 0.759 for predicting postoperative walking ability. The AUC of the mortality and walking ability predicting models were 0.791 and 0.818, respectively. CONCLUSIONS: Our models enabled rapid preoperative 1-year mortality and walking ability predictions in Asian elderly femoral neck fracture patients who planned for hip arthroplasty, with adequate predictive discrimination and calibration. Those rapid assessment models could help surgeons in making more reasonable clinical decisions and subsequently reducing the risk of potential medical dispute via quantitative and individualized prognosis assessments.

Combining autologous bone marrow buffy coat and angioconductive bioceramic rod grafting with advanced core decompression improves short-term outcomes in early avascular necrosis of the femoral head: a prospective, randomized, comparative study.

BACKGROUND: Treatment of avascular necrosis of the femoral head (ANFH) in young patients remains a clinical challenge. A current controversy is whether hip-preserving surgery results in better outcomes. The adverse effects of hip-preserving surgery are associated with the fill material for the necrotic areas. This study aims to evaluate the early effects of autologous bone marrow buffy coat (BBC) and angioconductive bioceramic rod (ABR) grafting with advanced core decompression (ACD) on early ANFH. METHODS: Forty-four (57 hips) patients with early ANFH from 2015 to 2020 were recruited for this study. They were randomized into two groups: group A received ACD, BBC, and ABR grafting; group B received treatment of ACD with ß-tricalcium phosphate (ß-TCP) granules and ABR grafting. The outcomes were assessed using the Harris Hip Scores (HHS) and survival rate analysis. The follow-up endpoint was defined as conversion to total hip arthroplasty (THA). RESULTS: Forty patients (51 hips) were ultimately included in this study for analysis. Compared with group B, patients in group A had higher postoperative function score (P = 0.032) and postoperative Harris Hip Scores (HHS) (P = 0.041). Kaplan-Meier analysis showed a trend that the survivorship of the femoral head was higher in group A than in group B. CONCLUSION: The short-term follow-up results showed that the autologous bone marrow buffy coat and angioconductive bioceramic rod grafting with advanced core decompression is effective in the treatment of early ANFH. TRIAL REGISTRATION: Chictr.org.cn , ChiCTR2000039595. Retrospectively registered on 11 February 2015.

STAT3/IL-6 dependent induction of inflammatory response in osteoblast and osteoclast formation in nanoscale wear particle-induced aseptic prosthesis loosening.

BACKGROUND: Aseptic loosening is the main reason for surgical revision after arthroplasty. Although a series of mechanisms have been explored, a specific therapeutic target is still desired. In the present study, we explored the role of the signal transducer and activator of the transcription (STAT)/interleukin-6 (IL-6) pathway in the induction of the inflammatory response in osteoblast and osteoclast formation during aseptic prosthesis loosening. METHODS: The expression of activated STAT3 was examined in osteoblasts treated with TiAl6V4 nanoparticles (TiPs) from materials used in prosthetics and specimens from particle-induced osteolysis (PIO) animal models. Inflammatory responses associated with the IL-6 family in osteoblasts were identified by Quantitative Real-time PCR. A mimicking coculture system was used to directly determine the number of activated osteoclasts in vitro, and immunohistochemical staining with tartrate-resistant acid phosphatase (TRAP) was used in vivo. CP690,550, an inhibitor of STAT3, was administered to examine the effect of STAT3 on the inflammatory response and osteoclast formation. RESULTS: STAT3 was activated in both nanoparticle-treated osteoblasts and PIO model animals. On the one hand, the activation of STAT3 mediated nanoparticle-induced IL-6-dependent inflammatory responses in osteoblasts. On the other hand, the activation of STAT3 induced receptor activator of nuclear factor kappa B ligand (RANKL) production and stimulated osteoclast formation. The application of the STAT3 inhibitor CP690,550 reduced the production of the IL-6 family and the formation of osteoclasts both in vitro and in vivo. CONCLUSION: STAT3 mediated inflammation-related signalling and osteoclast activation in nanoscale wear particle-induced aseptic loosening. Inhibition of STAT3 by tofacitinib may be a potential treatment for aseptic loosening.

Perioperative patient-specific factors-based nomograms predict short-term periprosthetic bone loss after total hip arthroplasty.

BACKGROUND: Although medical intervention of periprosthetic bone loss in the immediate postoperative period was recommended, not all the patients experienced periprosthetic bone loss after total hip arthroplasty (THA). Prediction tools that enrolled all potential risk factors to calculate an individualized prediction of postoperative periprosthetic bone loss were strongly needed for clinical decision-making. METHODS: Data of the patients who underwent primary unilateral cementless THA between April 2015 and October 2017 in our center were retrospectively collected. Candidate variables included demographic data and bone mineral density (BMD) in spine, hip, and periprosthetic regions that measured 1 week after THA. Outcomes of interest included the risk of postoperative periprosthetic bone loss in Gruen zone 1, 7, and total zones in the 1st postoperative year. Nomograms were presented based on multiple logistic regressions via R language. One thousand Bootstraps were used for internal validation. RESULTS: Five hundred sixty-three patients met the inclusion criteria were enrolled, and the final analysis was performed in 427 patients (195 male and 232 female) after the exclusion. The mean BMD of Gruen zone 1, 7, and total were decreased by 4.1%, 6.4%, and 1.7% at the 1st year after THA, respectively. 61.1% of the patients (261/427) experienced bone loss in Gruen zone 1 at the 1st postoperative year, while there were 58.1% (248/427) in Gruen zone 7 and 63.0% (269/427) in Gruen zone total. Bias-corrected C-index for risk of postoperative bone loss in Gruen zone 1, 7, and total zones in the 1st postoperative year were 0.700, 0.785, and 0.696, respectively. The most highly influential factors for the postoperative periprosthetic bone loss were primary diagnosis and BMD in the corresponding Gruen zones at the baseline. CONCLUSIONS: To the best of our knowledge, our study represented the first time to use the nomograms in estimating the risk of postoperative periprosthetic bone loss with adequate predictive discrimination and calibration. Those predictive models would help surgeons to identify high-risk patients who may benefit from anti-bone-resorptive treatment in the early postoperative period effectively. It is also beneficial for patients, as they can choose the treatment options based on a reasonable expectation following surgery.

10-year follow-up results of the prospective, double-blinded, randomized, controlled study on autologous bone marrow buffy coat grafting combined with core decompression in patients with avascular necrosis of the femoral head.

BACKGROUND: Avascular necrosis of the femoral head (ANFH) is a severely disabling disease of the hip. Several clinical trials have shown promising outcomes on the use of mesenchymal stem cells for the treatment of ANFH, but long-term clinical assessments are lacking. Previously, we reported the 2-year follow-up results of a prospective, double-blinded, randomized, controlled study on autologous bone marrow buffy coat grafting combined with core decompression in patients with ANFH. Here, we report the 10-year follow-up results of this study. METHODS: We recruited 43 (53 hips) patients from 2009 to 2010. The hips were randomly allocated to code decompression (CD) with or without bone marrow buffy coat (BBC) grafting. Participants underwent follow-up at 24, 60, and 120 months postoperatively. The visual analogue scale (VAS), Lequesne algofunctional index, and Western Ontario and McMaster Universities Arthritis Index (WOMAC) osteoarthritis scores were recorded. Survival rate analysis and prognostic factor analysis were performed. The endpoint was defined as progression to Ficat stage IV or conversion to hip arthroplasty. RESULTS: A total of 31 patients (41 hips) were included in the final analysis. The CD + BBC group had better subjective assessment scores than the CD group. The average survival times were 102.3 months and 78.1 months in the CD + BBC group and CD group, respectively (log-rank test, P = 0.029). In the univariate Cox proportional hazards regression model, age [hazard ratio (HR) = 1.079, P = 0.047] and preoperative Ficat stage (HR = 3.283, P = 0.028) indicated a high risk for progression, while the use of BBC (HR = 0.332, P = 0.042) indicated a low risk. Preoperative Ficat stage III was isolated as an independent risk factor for clinical failure in the multivariate model (HR = 3.743, P = 0.018). CONCLUSION: The 10-year follow-up results of this prospective, double-blinded, randomized, controlled study showed that the use of autologous BBC in combination with core decompression was more effective than the use of core decompression alone. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01613612 . Registered on 13 December 2011-retrospectively registered.

High periprosthetic bone mineral density measured in immediate postoperative period may not guarantee less periprosthetic bone loss in the proximal femur after cementless total hip arthroplasty - A retrospective study.

BACKGROUND: Total hip arthroplasty is the most common orthopaedic procedure for the end-stage hip diseases. Periprosthetic bone loss is closely related to the increased risk of implant loosening and periprosthetic fractures, but the predictive value of periprosthetic bone mineral density (BMD) measured immediately after surgery has not yet been investigated. METHODS: From April 2015 to October 2017, 64 patients with femoral neck fracture, hip osteoarthritis, femoral head necrosis, or developmental dysplasia of the hip underwent unilateral total hip arthroplasty. Demographic data, bone mineral density of the hip and spine, periprosthetic BMD of 7 Gruen zones, and radiographic parameters measured preoperatively, 1 week, 3 months, and 12 months after surgery were collected. A p value < 0.05 was considered to be statistically significant. RESULTS: Significant decreases of the periprosthetic BMD were found in Gruen zone 1 (- 8.0%; p < 0.05), Gruen zone 2 (- 6.3%; p < 0.05), Gruen zone 7 (- 8.6%; p < 0.05), and total Gruen zone (- 4.7%; p < 0.05) in the first postoperative year, compared with the values measured 1 week after surgery. The relationship between the preoperative BMD of the hip/spine and the BMD of Gruen zone 1 and Gruen zone 7 measured 1 week after surgery did not reach statistical significance. The multiple linear regression analysis illustrated that the bone loss in Gruen zone 7 at the end of the follow-up period was negatively affected (ß = - 0.703) by the BMD of Gruen zone 7 measured 1 week after surgery, with a R2 of 0.486 (p < 0.05). Similar results were also found in Gruen zone 1 (ß = - 0.448, R2 = 0.186; p < 0.05). CONCLUSION: There were marked decreases in periprosthetic BMD of the proximal femur in the first postoperative year. The predictive values of preoperative BMD of hip and spine on periprosthetic bone loss after THA were limited. Higher periprosthetic BMD measured in immediate postoperative period may not guarantee less periprosthetic bone loss in the proximal femur after cementless THA.

Efficiency of Zoledronic Acid in Inhibiting Accelerated Periprosthetic Bone Loss After Cementless Total Hip Arthroplasty in Osteoporotic Patients: A Prospective, Cohort Study.

OBJECTIVE: To investigate the influence of preoperative osteopenia/osteoporosis on periprosthetic bone loss after total hip arthroplasty (THA) and the efficiency of zoledronate (ZOL) treatment in periprosthetic bone preservation. METHODS: This multicenter, prospective cohort study was conducted in four centers between April 2015 and October 2017. Patients were assigned to Normal BMD, Osteopenia, and Osteoporosis+ZOL groups. Patients with osteopenia received daily oral calcium (600 mg/d) and vitamin D (0.5 µg/d), while patients in the Osteoporosis+ZOL group received additional ZOL annually (5 mg/year). Periprosthetic bone mineral density (BMD) in seven Gruen zones, radiographic parameters, Harris hip score, EuroQol 5-Dimensions (EQ-5D) score, and BMD in hip and spine were measured within 7 days, 3 months, 12 months postoperation and annually thereafter. RESULTS: A total of 266 patients were enrolled, while 81 patients that completed the first year follow-up were involved in the statistical analysis. The mean follow-up time was 1.3 years. There were significant decreases of mean BMD in total Gruen zones (-4.55%, P < 0.05) and Gruen zone 1 (-10.22%, P < 0.01) in patients with osteopenia during the first postoperative year. Patients in the Osteoporosis+ZOL group experienced a marked increase in BMD in Gruen zone 1 (+16%) at the first postoperative year, which had a significant difference when compared with the Normal BMD group (P < 0.05) and the Osteopenia Group (P < 0.001). Low preoperative BMD in hip and spine was predictive of bone loss in Gruen zone 1 at 12 months after THA in patients with normal BMD (R2 = 0.40, P < 0.05). CONCLUSIONS: Patients with osteopenia are prone to higher bone loss in the proximal femur after cementless total hip arthroplasty (THA). ZOL, not solely calcium and vitamin D, could prevent the accelerated periprosthetic bone loss after THA in patients with osteopenia and osteoporosis.

Small Heterodimer Partner Negatively Regulates TLR4 Signaling Pathway of Titanium Particles-Induced Osteolysis in Mice.

Arthroplasty has been widely performed worldwide. However, peri-prosthetic osteolysis and aseptic loosening induced by macrophages activated by wear particles still remain a predominant cause of long term prosthetic failure. Our study aimed to identify the role of small heterodimer partner (SHP) in secretion of proinflammatory cytokines by macrophages through Toll-like Recepters (TLR)s signaling pathway activated by wear particles both in vivo and in vitro. The effect of SHP on activation of TLR4 pathway and secretion of cytokines was observed in RAW264.7 cells and SHP gene over-expressed mice. Expression of TLR4, TRAF6, NEMO complex and proinflammatory cytokine TNF-α in macrophages stimulated by wear particles was up-regulated, while SHP was down-regulated. On the other hand, inhibition of SHP up-regulated the expression of NEMO complex and proinflammatory cytokine TNF-α in RAW264.7 stimulated by wear particles, while over-expression of SHP gene showed an opposite result. Over-expression of SHP gene could inhibit cranial osteolysis induced by wear particles in mice model. In conclusion, SHP down-regulates TLR4 signaling pathway to reduce osteolysis induced by titanium particles via in vitro and in vivo experimental models.

Identifying sensitive sources and key control handles for the reduction of greenhouse gas emissions from wastewater treatment.

This research investigates the effects of adjusting control handle values on greenhouse gas emissions from wastewater treatment, and reveals critical control handles and sensitive emission sources for control through the combined use of local and global sensitivity analysis methods. The direction of change in emissions, effluent quality and operational cost resulting from variation of control handles individually is determined using one-factor-at-a-time sensitivity analysis, and corresponding trade-offs are identified. The contribution of each control handle to variance in model outputs, taking into account the effects of interactions, is then explored using a variance-based sensitivity analysis method, i.e., Sobol's method, and significant second order interactions are discovered. This knowledge will assist future control strategy development and aid an efficient design and optimisation process, as it provides a better understanding of the effects of control handles on key performance indicators and identifies those for which dynamic control has the greatest potential benefits. Sources with the greatest variance in emissions, and therefore the greatest need to monitor, are also identified. It is found that variance in total emissions is predominantly due to changes in direct N2O emissions and selection of suitable values for wastage flow rate and aeration intensity in the final activated sludge reactor is of key importance. To improve effluent quality, costs and/or emissions, it is necessary to consider the effects of adjusting multiple control handles simultaneously and determine the optimum trade-off.

Multi-objective optimisation of wastewater treatment plant control to reduce greenhouse gas emissions.

This study investigates the potential of control strategy optimisation for the reduction of operational greenhouse gas emissions from wastewater treatment in a cost-effective manner, and demonstrates that significant improvements can be realised. A multi-objective evolutionary algorithm, NSGA-II, is used to derive sets of Pareto optimal operational and control parameter values for an activated sludge wastewater treatment plant, with objectives including minimisation of greenhouse gas emissions, operational costs and effluent pollutant concentrations, subject to legislative compliance. Different problem formulations are explored, to identify the most effective approach to emissions reduction, and the sets of optimal solutions enable identification of trade-offs between conflicting objectives. It is found that multi-objective optimisation can facilitate a significant reduction in greenhouse gas emissions without the need for plant redesign or modification of the control strategy layout, but there are trade-offs to consider: most importantly, if operational costs are not to be increased, reduction of greenhouse gas emissions is likely to incur an increase in effluent ammonia and total nitrogen concentrations. Design of control strategies for a high effluent quality and low costs alone is likely to result in an inadvertent increase in greenhouse gas emissions, so it is of key importance that effects on emissions are considered in control strategy development and optimisation.

Identifying key sources of uncertainty in the modelling of greenhouse gas emissions from wastewater treatment.

This study investigates sources of uncertainty in the modelling of greenhouse gas emissions from wastewater treatment, through the use of local and global sensitivity analysis tools, and contributes to an in-depth understanding of wastewater treatment modelling by revealing critical parameters and parameter interactions. One-factor-at-a-time sensitivity analysis is used to screen model parameters and identify those with significant individual effects on three performance indicators: total greenhouse gas emissions, effluent quality and operational cost. Sobol's method enables identification of parameters with significant higher order effects and of particular parameter pairs to which model outputs are sensitive. Use of a variance-based global sensitivity analysis tool to investigate parameter interactions enables identification of important parameters not revealed in one-factor-at-a-time sensitivity analysis. These interaction effects have not been considered in previous studies and thus provide a better understanding wastewater treatment plant model characterisation. It was found that uncertainty in modelled nitrous oxide emissions is the primary contributor to uncertainty in total greenhouse gas emissions, due largely to the interaction effects of three nitrogen conversion modelling parameters. The higher order effects of these parameters are also shown to be a key source of uncertainty in effluent quality.