Exploring the influence of sulfadiazine-induced stress on antibiotic removal and transformation pathway using microalgae Chlorella sp.

Sulfadiazine (SDZ) is a kind of anti-degradable antibiotics that is commonly found in wastewater, but its removal mechanism and transformation pathway remain unclear in microalgal systems. This study investigated the effects of initial algae concentration and SDZ-induced stress on microalgal growth metabolism, SDZ removal efficiency, and transformation pathways during Chlorella sp. cultivation. Results showed that SDZ had an inhibitory effect on the growth of microalgae, and increasing the initial algal biomass could alleviate the inhibitory effect of SDZ. When the initial algal biomass of Chlorella sp. was increased to 0.25 g L-1, the SDZ removal rate could reach 53.27%-89.07%. The higher the initial algal biomass, the higher the SOD activity of microalgae, and the better the protective effect on microalgae, which was one of the reasons for the increase in SDZ removal efficiency. Meanwhile, SDZ stress causes changes in photosynthetic pigments, lipids, total sugars and protein content of Chlorella sp. in response to environmental changes. The main degradation mechanisms of SDZ by Chlorella sp. were biodegradation (37.82%) and photodegradation (23%). Most of the degradation products of SDZ were less toxic than the parent compound, and the green algae were highly susceptible to SDZ and its degradation products. The findings from this study offered valuable insights into the tradeoffs between accumulating microalgal biomass and antibiotic toxic risks during wastewater treatment, providing essential direction for the advancement in future research and full-scale application.

Recombinant human IL-37 attenuates acute cardiac allograft rejection in mice.

BACKGROUND: Allograft rejection remains a major obstacle to long-term graft survival. Although previous studies have demonstrated that IL-37 exhibited significant immunomodulatory effects in various diseases, research on its role in solid organ transplantation has not been fully elucidated. In this study, the therapeutic effect of recombinant human IL-37 (rhIL-37) was evaluated in a mouse cardiac allotransplantation model. METHODS: The C57BL/6 recipients mouse receiving BALB/c donor hearts were treated with rhIL-37. Graft pathological and immunohistology changes, immune cell populations, and cytokine profiles were analyzed on postoperative day (POD) 7. The proliferative capacities of Th1, Th17, and Treg subpopulations were assessed in vitro. Furthermore, the role of the p-mTOR pathway in rhIL-37-induced CD4+ cell inhibition was also elucidated. RESULTS: Compared to untreated groups, treatment of rhIL-37 achieved long-term cardiac allograft survival and effectively alleviated allograft rejection indicated by markedly reduced infiltration of CD4+ and CD11c+ cells and ameliorated graft pathological changes. rhIL-37 displayed significantly less splenic populations of Th1 and Th17 cells, as well as matured dendritic cells. The percentages of Tregs in splenocytes were significantly increased in the therapy group. Furthermore, rhIL-37 markedly decreased the levels of TNF-α and IFN-γ, but increased the level of IL-10 in the recipients. In addition, rhIL-37 inhibited the expression of p-mTOR in CD4+ cells of splenocytes. In vitro, similar to the in vivo experiments, rhIL-37 caused a decrease in the proportion of Th1 and Th17, as well as an increase in the proportion of Treg and a reduction in p-mTOR expression in CD4+ cells. CONCLUSIONS: We demonstrated that rhIL-37 effectively suppress acute rejection and induce long-term allograft acceptance. The results highlight that IL-37 could be novel and promising candidate for prevention of allograft rejection.

[Musculoskeletal multibody dynamics investigation for the different medial-lateral installation position of the femoral component in unicompartmental knee arthroplasty].

The surgical installation accuracy of the components in unicompartmental knee arthroplasty (UKA) is an important factor affecting the joint function and the implant life. Taking the ratio of the medial-lateral position of the femoral component relative to the tibial insert (a/A) as a parameter, and considering nine installation conditions of the femoral component, this study established the musculoskeletal multibody dynamics models of UKA to simulate the patients' walking gait, and investigated the influences of the medial-lateral installation positions of the femoral component in UKA on the contact force, joint motion and ligament force of the knee joint. The results showed that, with the increase of a/A ratio, the medial contact force of the UKA implant was decreased and the lateral contact force of the cartilage was increased; the varus rotation, external rotation and posterior translation of the knee joint were increased; and the anterior cruciate ligament force, posterior cruciate ligament force and medial collateral ligament force were decreased. The medial-lateral installation positions of the femoral component in UKA had little effect on knee flexion-extension movement and lateral collateral ligament force. When the a/A ratio was less than or equalled to 0.375, the femoral component collided with the tibia. In order to prevent the overload on the medial implant and lateral cartilage, the excessive ligament force, and the collision between the femoral component and the tibia, it is suggested that the a/A ratio should be controlled within the range of 0.427-0.688 when the femoral component is installed in UKA. This study provides a reference for the accurate installation of the femoral component in UKA.

Construction of the Adjusted Scoliosis 3D Finite Element Model and Biomechanical Analysis under Gravity.

OBJECTIVE: Adolescent idiopathic scoliosis (AIS) is a three-dimensional structural deformity of the spine caused by the disruption of the biomechanical balance of the spine. However, the current biomechanical modeling and analysis methods of scoliosis cannot really describe the real state of the spine. This study aims to propose a high-precision biomechanical modeling and analysis method that can reflect the spinal state under gravity and provide a theoretical basis for therapeutics. METHODS: Combining CT and X-ray images of AIS patients, this study constructed an adjusted three-dimensional model and FE model of the spine corresponding to the patient's gravity position, including vertebral bodies, intervertebral discs, ribs, costal cartilage, ligaments, and facet cartilage. Then, the displacement and stress of the spine under gravity were analyzed. RESULTS: A model of the T1-Sacrum with 1.7 million meshes was constructed. After adding the gravity condition, the maximum displacement point was at T1 of thoracic vertebra (20.4 mm). The analysis indicates that the stress on the lower surface of the vertebral body in thoracolumbar scoliosis tended to be locally concentrated, especially on the concave side of the primary curvature's vertebral body (the maximum stress on the lower surface of T9 is 32.33 MPa) and the convex side of the compensatory curvature's vertebral body (the maximum stress on the lower surface of L5 is 41.97 MPa). CONCLUSION: This study provides a high-precision modeling and analysis method for scoliosis with full consideration of gravity. The reliability of the method was verified based on patient data. This model can be used to analyze the biomechanical characteristics of patients in the treatment plan design stage.

Effect of Hip Joint Center on Multi-body Dynamics and Contact Mechanics of Hip Arthroplasty for Crowe IV Dysplasia.

OBJECTIVE: To investigate the hip joint forces, Von Mises stress, contact pressure and micro-motion of hip prosthesis for developmental dysplasia of the hip (DDH) patients under different hip joint centers using musculoskeletal (MSK) multi-body dynamics and finite element analysis. METHODS: Both MSK multi-body dynamics model and finite element (FE) model were based on CT data of a young female DDH patient with total hip replacement and were developed to study the biomechanics of the S-ROM hip prosthesis. The same offset of hip joint center along all six orientations compared with the standard position was set to predict its effects on both MSK multi-body dynamics and contact mechanics during one gait cycle. RESULTS: The hip joint forces in the entire walking gait cycle showed two peak values and clear differences between them under different hip joint centers. The hip joint force increased when the hip joint center moved posteriorly (2101 N) and laterally (1969 N) to the anatomical center (1848 N) at the first peak by 13.7% and 6.6%, respectively. The hip joint force increased sharply when the hip center deviated laterally (2115 N) and anteriorly (2407 N), respectively, from the standard position (1742 N) at the second peak. For the sleeve of the S-ROM prosthesis, the maximum Von Mises stress and contact pressure of the sleeve increased if the hip joint center deviated from the anatomical center posteriorly at the first peak. However, the Von Mises stresses and contact pressure increased at anterior and lateral orientations, compared to that of the standard position at the second peak. Small changes were observed for the maximum relative sliding distance along most of the orientations at both peaks except in the lateral and medial orientations, in which an increase of 8.6% and a decrease of 13.6% were observed, respectively. CONCLUSION: The hip joint center obviously influenced the hip joint forces, stress, contact pressure and micro-motion of the hip implant for this female patient.

[Musculoskeletal multibody dynamics investigation of posterior-stabilized total knee prosthesis].

Posterior-stabilized total knee prostheses have been widely used in orthopedic clinical treatment of knee osteoarthritis, but the patients and surgeons are still troubled by the complications, for example severe wear and fracture of the post, as well as prosthetic loosening. Understanding the in vivo biomechanics of knee prostheses will aid in the decrease of postoperative prosthetic revision and patient dissatisfaction. Therefore, six different designs of posterior-stabilized total knee prostheses were used to establish the musculoskeletal multibody dynamics models of total knee arthroplasty respectively, and the biomechanical differences of six posterior-stabilized total knee prostheses were investigated under three simulated physiological activities: walking, right turn and squatting. The results showed that the post contact forces of PFC Sigma and Scorpio NGR prostheses were larger during walking, turning right, and squatting, which may increase the risk of the fracture and wear as well as the early loosening. The post design of Gemini SL prosthesis was more conductive to the knee internal-external rotation and avoided the edge contact and wear. The lower conformity design in sagittal plane and the later post-cam engagement resulted in the larger anterior-posterior translation. This study provides a theoretical support for guiding surgeon selection, improving posterior-stabilized prosthetic design and reducing the prosthetic failure.

SENP1 promotes triple-negative breast cancer invasion and metastasis via enhancing CSN5 transcription mediated by GATA1 deSUMOylation.

TNBC is characterized by high incidence of visceral metastasis and lacks effective clinical targets. This study aims to delineate the molecular mechanisms of SENP1 in TNBC invasion and metastasis. By using IHC to test the SENP1 expression in TNBC tissues, we analyzed the relationship between SENP1 expression and TNBC prognosis. We showed that SENP1 expression was higher in TNBC tumor tissues and related to TNBC prognosis, supporting SENP1 as an independent risk factor. High expression of SENP1 was significantly associated with histologic grade and tumor lymph node invasion. Intriguingly, the expression levels of SENP1 in TNBC tumors were significantly correlated with that of CSN5, GATA1 and ZEB1. Importantly, SENP1 promoted TNBC cell migration and invasion by regulating ZEB1 deubiquitination and expression through CSN5. Further studies showed that deSUMOylation at lysine residue K137 of GATA1 enhanced the binding of GATA1 to the CSN5 promoter and transactivated CSN5 expression. In addition, we showed that ZEB1 is deubiquitinated at lysine residue K1108. Our in vivo studies also indicated that reduction in SENP1 expression upregulated GATA1 SUMOylation, and thus resulted in decreased expression of CSN5 and ZEB1 in the tumor microenvironment, which decelerated TNBC progression and metastasis. SENP1 promoted CSN5-mediated ZEB1 protein degradation via deSUMOylation of GATA1, and thus influenced TNBC progression. These findings suggest that SENP1 could be utilized as a potential target for blockade of TNBC development and thus provide a totally new approach for TNBC treatment.

Molecular subtype classification of breast cancer using established radiomic signature models based on 18F-FDG PET/CT images.

Backgrounds: To evaluate the predictive power of 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) derived radiomics in molecular subtype classification of breast cancer (BC). Methods: A total of 273 primary BC patients who underwent a 18F-FDG PET/CT imaging prior to any treatment were included in this retrospective study, and the values of five conventional PET parameters were calculated, including the maximum standardized uptake value (SUVmax), SUVmean, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The ImageJ 1.50i software and METLAB package were used to delineate the contour of BC lesions and extract PET/CT derived radiomic features reflecting heterogeneity. Then, the least absolute shrinkage and selection operator (LASSO) algorithm was used to select optimal subsets of radiomic features and establish several corresponding radiomic signature models. The predictive powers of individual PET parameters and developed PET/CT derived radiomic signature models in molecular subtype classification of BC were evaluated by using receiver operating curves (ROCs) analyses with areas under the curve (AUCs) as the main outcomes. Results: All of the three SUV parameters but not MTV nor TLG were found to be significantly underrepresented in luminal and non-triple (TN) subgroups in comparison with corresponding non-luminal and TN subgroups. Whereas, no significant differences existed in all the five conventional PET parameters between human epidermal growth factor receptor 2+ (HER2+) and HER2- subgroups. Furthermore, all of the developed radiomic signature models correspondingly exhibited much more better performances than all the individual PET parameters in molecular subtype classification of BC, including luminal vs. non-luminal, HER2+ vs. HER2-, and TN vs. non-TN classification, with a mean value of 0.856, 0.818, and 0.888 for AUC. Conclusions: PET/CT derived radiomic signature models outperformed individual significant PET parameters in molecular subtype classification of BC.

Effect of Rotator Cuff Deficiencies on Muscle Forces and Glenohumeral Contact Force After Anatomic Total Shoulder Arthroplasty Using Musculoskeletal Multibody Dynamics Simulation.

Anatomic total shoulder arthroplasty (ATSA) is widely used to treat the diseases of the glenohumeral (GH) joint. However, the incidence of rotator cuff tears after ATSA increases during follow-up. The effects of rotator cuff deficiencies after ATSA on the biomechanics of the GH joint are to be investigated. In this study, a musculoskeletal multibody dynamics model of ATSA was established using a force-dependent kinematics (FDK) method. The biomechanical effects were predicted during arm abduction under different rotator cuff deficiencies. The deltoid forces were increased under the rotator cuff deficiencies, the maximum deltoid forces were increased by 36% under the subscapularis deficiency and by 53% under the supraspinatus, infraspinatus, subscapularis, and teres minor deficiencies. The maximum GH contact forces were decreased by 11.3% under supraspinatus and infraspinatus deficiencies but increased by 24.8% under subscapularis deficiency. The maximum subscapularis force was decreased by 17% under only infraspinatus tear during arm abduction. The results suggested that the changes in the biomechanics of the GH joint induced by rotator cuff deficiencies after ATSA increase the deltoid muscle energy expenditure and joint instability, which result in postoperative less satisfactory clinical outcomes. The changes in rotator cuff muscle forces deserve more attention for understanding the evolution of rotator cuff tear after ATSA.

Identification of markers associated with brain metastasis from breast cancer through bioinformatics analysis and verification in clinical samples.

BACKGROUND: Brain metastasis from breast cancer (BC) is an important cause of BC-related death. The present study aimed to identify markers of brain metastasis from BC. METHODS: Datasets were downloaded from the public databases Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Weighted gene co-expression network analysis (WGCNA) was performed to identify metastasis-associated genes (MAGs). Least absolute shrinkage and selection operator (LASSO) Cox proportional hazards regression models were constructed for screening key MAGs. Survival analysis and receiver operating characteristic (ROC) curves were used for evaluating the prognostic value. The factors associated with tumor metastasis were integrated to create a nomogram of TCGA data using R software. Gene Set Enrichment Analyses (GSEA) was performed for detecting the potential mechanisms of identified MAGs. Immunohistochemistry (IHC) was used to verify the expression of the key genes in clinical samples. RESULTS: The genes in 2 modules were identified to be significantly associated with metastasis through WGCNA. LASSO Cox proportional hazards regression models were constructed successfully. Subsequently, a clinical prediction model was constructed, and a nomogram was mapped, which had better sensitivity and specificity for BC metastasis. Two key genes, discs large homolog 3 (DLG3) and growth factor independence 1 (GFI1), were highly expressed in clinical samples, and the expression of these 2 genes was associated with patients' survival time. CONCLUSIONS: We successfully constructed a clinical prediction model for brain metastasis from BC, and identified that the expression of DLG3 and GFI1 were strongly associated with brain metastasis from BC.

Effects of Daily Activities and Position on Kinematics and Contact Mechanics of Dual Mobility Hip Implant.

Dual mobility hip implants have been widely introduced to overcome dislocation in recent years. However, the potential influence of different gaits on kinematics and contact mechanics for dual mobility hip implants is still unclear. Furthermore, a large range of motion coupling with the implant position, especially high inclination or anteversion angle, may result in poor kinematics and contact mechanics. A previously developed dynamic finite element method was adopted in this study to examine the kinematics and corresponding stability of dual mobility hip implants under different gaits coupling with different inclinations or anteversion angles. The results showed only inner relative sliding under knee-bending for dual mobility hip implants under moderate inclination and anteversion angles, whereas an anteversion angle of 25° induced both impingement and consequent relative sliding of the outer articulation. However, the impingement (between the stem neck and the liner inner rim) indeed happened under stair-climbing and sitting-down/stand-up as well as combined movements when inclination and anteversion angles were set as 45° and 0°, respectively, and this finally led to relative sliding at the outer articulation. A high inclination angle did not worsen both the impingement and related outer sliding compared to modest inclination and anteversion angles of the liner, but a high anteversion angle prolonged the period of both the impingement and the outer relative sliding. The extreme motions and high anteversion angles are hardly inevitable, and they indeed lead to motions at both articulations for dual mobility hip implants.

Effects of interference assembly of a tibial insert on the tibiofemoral contact mechanics in total knee replacement.

Tibial locking mechanism design is adopted to limit the backside micromotion in fixed-bearing total knee replacement. However, the effect of the interference assembly of a tibial insert on the tibiofemoral contact mechanics was usually ignored. Finite element model of a fixed-bearing total knee replacement with full peripheral locking mechanism was established to simulate the interference assembly of the tibial insert, and the corresponding effects on the tibiofemoral contact mechanics were predicted. Due to the interference assembly of the tibial insert, a maximum Mises stress of 3.24 MPa was found for the tibial insert before loading. Furthermore, the contact stress was increased by 8.77%, and the contact area was decreased by 5.43% under peak load. The interference assembly of the tibial insert in a fixed-bearing total knee replacement changed the tibiofemoral contact mechanics. This study indicated that the level of interference fit should be cautiously designed for the tibial locking mechanism in fixed-bearing total knee replacement for balancing the articular surface wear and the backside wear of the modular tibial insert.

High Tibial Osteotomy: Review of Techniques and Biomechanics.

High tibial osteotomy becomes increasingly important in the treatment of cartilage damage or osteoarthritis of the medial compartment with concurrent varus deformity. HTO produces a postoperative valgus limb alignment with shifting the load-bearing axis of the lower limb laterally. However, maximizing procedural success and postoperative knee function still possess many difficulties. The key to improve the postoperative satisfaction and long-term survival is the understanding of the vital biomechanics of HTO in essence. This review article discussed the alignment principles, surgical technique, and fixation plate of HTO as well as the postoperative gait, musculoskeletal dynamics, and contact mechanics of the knee joint. We aimed to highlight the recent findings and progresses on the biomechanics of HTO. The biomechanical studies on HTO are still insufficient in the areas of gait analysis, joint kinematics, and joint contact mechanics. Combining musculoskeletal dynamics modelling and finite element analysis will help comprehensively understand in vivo patient-specific biomechanics after HTO.

Biomechanics and wear comparison between mechanical and kinematic alignments in total knee arthroplasty.

The uses of mechanical and kinematic alignments in total knee arthroplasty are under debate in recent clinical investigations. In this study, the differences in short-term biomechanics and long-term wear volume between mechanical and kinematic alignments in total knee arthroplasty were investigated, based on a subject-specific musculoskeletal multi-body dynamics model during walking gait simulation. An increase of 8.2% in the peak tibiofemoral medial contact force, a posterior contact translation by maximum 4.7 mm and a decrease of 5.5% in the wear volume after a 10-million-cycle simulation were predicted in the kinematic alignment, compared with the mechanical alignment. Nevertheless, the tibiofemoral contact mechanics, the range of motions and the long-term wear were not markedly different between mechanical and kinematic alignments. Furthermore, the mechanical alignment with a posterior tibial slope similar to that under the kinematic alignment was found to produce similar anterior-posterior translation and the range of motion, and an approximate wear volume, compared with the kinematic alignment. The ligament forces under the kinematic alignment were influenced markedly by as much as 25%, 50% and 77% for the medial collateral ligament, lateral collateral ligament and posterior cruciate ligament forces, respectively. And, a maximum increase of 40% for patellofemoral contact force was predicted under the kinematic alignment. These findings suggest that the kinematic alignment is an alternative alignment principle but no marked advantages in biomechanics and wear to the mechanical alignment. The adverse effects of the kinematic alignment on patella loading and soft tissue forces should be noticed.

Effect of inclination and anteversion angles on kinematics and contact mechanics of dual mobility hip implants.

BACKGROUND: Steep inclination and excessive anteversion angles of acetabular cups could result in adverse edge-loading. This, in turn, increases contact pressure and impingement risk for traditional artificial hip joints. However, the influence of high inclination and anteversion angles on both the kinematics and contact mechanics of dual mobility hip implants has rarely been examined. METHODS: This study focuses on investigating both the kinematics and contact mechanics of a dual mobility hip implant under different inclination and anteversion angles using a dynamic explicit finite element method developed in a previous study. FINDINGS: The results showed that an inclination angle of both the back shell and liner ranging from 30° to 70° had little influence on the maximum contact pressure and the accumulated sliding distance of inner and outer surfaces of the liner under normal walking gait. The same results were obtained for an anteversion angle of the liner varying between -20° and +20°. However, when the anteversion angle of the liner was beyond this range, the contact between the femoral neck and the inner rim of the liner occurred. Consequently, this caused a relative rotation at the outer articulation. INTERPRETATIONS: This suggests that both inclination and modest anteversion angles have little influence on the kinematics and contact mechanics of dual mobility hip implants. However, too excessive anteversion angle could result in a rotation for this kind of hip implant at both articulations.

Concurrent prediction of ground reaction forces and moments and tibiofemoral contact forces during walking using musculoskeletal modelling.

Ground reaction forces and moments (GRFs and GRMs) measured from force plates in a gait laboratory are usually used as the input conditions to predict the knee joint forces and moments via musculoskeletal (MSK) multibody dynamics (MBD) model. However, the measurements of the GRFs and GRMs data rely on force plates and sometimes are limited by the difficulty in some patient's gait patterns (e.g. treadmill gait). In addition, the force plate calibration error may influence the prediction accuracy of the MSK model. In this study, a prediction method of the GRFs and GRMs based on elastic contact element was integrated into a subject-specific MSK MBD modelling framework of total knee arthroplasty (TKA), and the GRFs and GRMs and knee contact forces (KCFs) during walking were predicted simultaneously with reasonable accuracy. The ground reaction forces and moments were predicted with an average root mean square errors (RMSEs) of 0.021 body weight (BW), 0.014 BW and 0.089 BW in the antero-posterior, medio-lateral and vertical directions and 0.005 BW•body height (BH), 0.011 BW•BH, 0.004 BW•BH in the sagittal, frontal and transverse planes, respectively. Meanwhile, the medial, lateral and total tibiofemoral (TF) contact forces were predicted by the developed MSK model with RMSEs of 0.025-0.032 BW, 0.018-0.022 BW, and 0.089-0.132 BW, respectively. The accuracy of the predicted medial TF contact force was improved by 12% using the present method. The proposed method can extend the application of the MSK model of TKA and is valuable for understanding the in vivo knee biomechanics and tribological conditions without the force plate data.

Effect of friction and clearance on kinematics and contact mechanics of dual mobility hip implant.

The dual mobility hip implant has been introduced recently and increasingly used in total hip replacement to maintain the stability and reduce the risk of post-surgery dislocation. However, the kinematics and contact mechanisms of dual mobility hip implants have not been investigated in detail in the literature. Therefore, finite element method was adopted in this study to investigate dynamics and contact mechanics of a typical metal-on-polymer dual mobility hip implant under different friction coefficient ratios between the inner and the outer articulations and clearances/interferences between the ultra-high-molecular-weight polyethylene liner and the metal back shell. A critical ratio of friction coefficients between the two pairs of contact interfaces was found to mainly determine the rotating surfaces. Furthermore, an initial clearance between the liner and the back shell facilitated the rotation of the liner while an initial interference prevented such a motion at the outer articulating interface. In addition, the contact area and the sliding distance at the outer articulating surface were markedly greater than those at the inner cup-head interface, potentially leading to extensive wear at the outer surface of the liner.

Finite element analysis of sliding distance and contact mechanics of hip implant under dynamic walking conditions.

An explicit finite element method was developed to predict the dynamic behavior of the contact mechanics for a hip implant under normal walking conditions. Two key parameters of mesh sensitivity and time steps were examined to balance the accuracy and computational cost. Both the maximum contact pressure and accumulated sliding distance showed good agreement with those in the previous studies using the implicit finite element analysis and analytical methods. Therefore, the explicit finite element method could be used to predict the contact pressure and accumulated sliding distance for an artificial hip joint simultaneously in dynamic manner.

Application of 3D printed customized external fixator in fracture reduction.

INTRODUCTION: Long bone fracture is common in traumatic osteopathic patients. Good reduction is beneficial for bone healing, preventing the complications such as delayed union, nonunion, malunion, but is hard to achieve. Repeated attempts during the surgery would increase the operation time, cause new damage to the fracture site and excessive exposure to radiation. Robotic and navigation techniques can help improve the reduction accuracy, however, the high cost and complexity of operation have limited their clinical application. MATERIALS AND METHODS: We combined 3D printing with computer-assisted reduction technique to develop a customised external fixator with the function of fracture reduction. The original CT data obtained by scanning the fracture was imported to computer for reconstructing and reducing the 3D image of the fracture, based on which the external fixator (named as Q-Fixator) was designed and then fabricated by 3D printing techniques. The fracture reduction and fixation was achieved by connecting the pins inserted in the bones with the customised Q-Fixator. Experiments were conducted on three fracture models to demonstrate the reduction results. RESULTS: Good reduction results were obtained on all three fractured bone models, with an average rotation of 1.21°(± 0.24), angulation of 1.84°(± 0.28), and lateral displacement of 2.22 mm(± 0.62). CONCLUSIONS: A novel customised external fixator for long bone fracture reduction was readily developed using 3D printing technique. The customised external fixator had the advantages of easy manipulation, accurate reduction, minimally invasion and experience-independence. Future application of the customised external fixator can be extended to include the fixation function with stress adjustment and potentially optimise the fracture healing process.

Modulation of BAG-1 expression alters the sensitivity of breast cancer cells to tamoxifen.

BACKGROUND: BAG-1 (bcl-2 associated athanogene) is a multifunctional protein that protects cells from a wide range of apoptotic stimuli including radiation, hypoxia and chemotherapeutic agents. Overexpression of cytoplasmic BAG-1 has been associated with the increased survival and decreased response to treatment with tamoxifen (TAM) in breast cancer. We attempted to assess the expression of BAG-1 in the human breast cancer cells that are resistant to treatment with 4-OH TAM and effect of altered BAG-1 expression on their sensitivity to 4-OH TAM. METHODS: BAG-1 expression was examined in the MCF-7 cells that became resistant to 4-OH TAM. The 4-OH TAM-resistant MCF-7 cells were then transfected with the BAG-1 siRNA and the 4-OH TAM-sensitive MCF-7 cells with the plasmids carrying the human BAG-1 isoform-specific expression constructs respectively to investigate the effect of BAG-1 on the TAM-induced apoptosis. RESULTS: Our results showed that the TAM-resistant MCF-7 (TAMR/MCF-7) cells expressed higher level of BAG-1 than that of the MCF-7 cells. Down-regulation of BAG-1 significantly enhanced the sensitivity of the TAMR/MCF-7 cells to TAM treatment. Additionally, we found that BAG-1 p50 was the only isoform that inhibited the TAM-induced apoptosis in the MCF-7 cells, while the other isoforms had little effect. CONCLUSION: Our study indicated that up and down regulations of the BAG-1 expression were associated with the decreased and increased sensitivity to 4-OH TAM in the estrogen receptor-positive (ER+) human breast cancer cell line MCF-7 respectively, and distinct isoforms of BAG-1 had different anti-apoptotic ability in breast cancer cells treated with the 4-OH TAM.