Wnt signaling and tumors (Review).

Wnt signaling is a highly conserved evolutionary pathway that plays a key role in regulation of embryonic development, as well as tissue homeostasis and regeneration. Abnormalities in Wnt signaling are associated with tumorigenesis and development, leading to poor prognosis in patients with cancer. However, the pharmacological effects and mechanisms underlying Wnt signaling and its inhibition in cancer treatment remain unclear. In addition, potential side effects of inhibiting this process are not well understood. Therefore, the present review outlines the role of Wnt signaling in tumorigenesis, development, metastasis, cancer stem cells, radiotherapy resistance and tumor immunity. The present review further identifies inhibitors that target Wnt signaling to provide a potential novel direction for cancer treatment. This may facilitate early application of safe and effective drugs targeting Wnt signaling in clinical settings. An in-depth understanding of the mechanisms underlying inhibition of Wnt signaling may improve the prognosis of patients with cancer.

Pelvic packing or endovascular interventions: Which should be given priority in managing hemodynamically unstable pelvic fractures? A systematic review and a meta-analysis.

Background: Pelvic fractures in trauma patients can be associated with substantial massive hemorrhage. Hemostasis interventions mainly consist of pelvic packing (PP) and endovascular intervention (EI), such as angiography-embolization (AE) and resuscitative endovascular balloon occlusion of the aorta (REBOA). Whether PP or EI should be prioritized for the management of hemodynamic unstable patients with pelvic fractures remains under debate. This meta-analysis aimed to establish the evidence-based recommendations for the management of hemodynamic unstable patients. Materials and methods: PubMed, CENTRAL, and EMBASE databases were searched for articles published from January 1, 2000 to January 31, 2023. Eligible studies, such as retrospective cohort studies, propensity score matching studies, prospective cohort studies, observational cohort studies, quasi-randomized clinical trials evaluating PP and EI (AE or REBOA) for the management of patients with hemodynamically unstable pelvic fractures, were included. Mean Difference (MD), relative risk (RR), and 95 % confidence intervals (CI) were calculated using fixed- or random-effects models depending on the heterogeneity of included trials. We compared the effectiveness of the two methods in terms of mortality, unstable fracture pattens, injury severity score (ISS), systolic blood pressure (SBP), lactate (LA), base deficiency (BE), hemoglobin preoperatively, blood transfusion requirement, the time to and of operation, complications. Results: Overall, 15 trials enrolling 1136 patients were analyzed, showing a total mortality rate of 28.4 % (323/1136). No effect of PP preference on the ISS (PP 36.4 ± 10.4 vs. EI 34.5 ± 12.7), SBP (PP 81.1 ± 24.3 mmHg vs. EI 94.2 ± 32.4 mmHg), LA (PP 4.66 ± 2.72 mmol/L vs. 4.85 ± 3.45 mmol/L), BE (PP 8.14 ± 5.64 mmol/L vs. 6.66 ± 5.68 mmol/L), and unstable fracture patterns (RR = 1.10, 95 % CI [0.63, 1.92]) was observed. PP application was associated with lower preoperative hemoglobin level (PP 8.11 ± 2.28 g/dL vs. EI 8.43 ± 2.43 g/dL, p < 0.05), more preoperative transfusion (MD = 2.53, 95 % CI [0.01, 5.06]), less postoperative transfusion within the first 24 h (MD = -1.09, 95 % CI [-1.96, -0.22]), shorter waiting time to intervention (MD = -0.93, 95 % CI [-1.54, -0.31]), and shorter operation time of intervention (MD = -0.41, 95 % CI [-0.52, -0.30]). PP had lower mortality rate owing to uncontrolled hemorrhage in the acute phase (RR = 0.41, 95 % CI [0.22, 0.79]). There was neither difference in mortality due to other complications (RR = 1.60, 95 % CI [0.79, 3.24]), nor in total mortality (RR = 0.92, 95%CI [0.49, 1.74]) (p > 0.05). Conclusions: PP showed advantages of reducing the amount of postoperative transfusion, shortening the time of waiting and operating, and decreasing mortality due to uncontrolled hemorrhage in the acute phase without raising the odds of mortality due to complications. PP, a reliable hemostatic method, should be prioritized for resuscitating most pelvic fractures with hemodynamically unstable, especially in case of bleeding from veins and fracture sites, as well as inadequate EI.

A probabilistic approach for assessing the mechanical performance of intertrochanteric fracture stabilized with proximal femoral nail antirotation.

Maintaining post-operative mechanical stability is crucial for successfully healing intertrochanteric fractures treated with the Proximal Femoral Nail Antirotation (PFNA) system. This stability is primarily dependent on the bone mineral density (BMD) and strain on the fracture. Current PFNA failure analyses often overlook the uncertainties related to BMD and body weight (BW). Therefore, this study aimed to develop a probabilistic model using finite element modeling and engineering reliability analysis to assess the post-operative performance of PFNA under various physiological loading conditions. The model predictions were validated through a series of experimental test. The results revealed a negative nonlinear relationship between the BMD and compressive strain. Conversely, the BW was positively and linearly correlated with the compressive strain. Importantly, the compressive strain was more sensitive to BW than to BMD when the BMD exceeded 0.6 g/cm3. Potential trabecular bone compression failure is also indicated if BMD is equal to or below 0.15 g/cm3 and BW increases to approximately 2.5 times the normal or higher. This study emphasizes that variations in the BMD significantly affect the probability of failure of a PFNA system. Thus, careful planning of post-operative physical therapy is essential. For patients aged > 50 years restrictions on high-intensity activities are advised, while limiting strenuous movements is recommended for those aged > 65 years.

Effects of physical activity and sedentary behavior on serum vitamin D in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex, heterogeneous disease with multiple extrapulmonary manifestations, among which vitamin D deficiency and insufficiency are very common in COPD and are associated with the health status and clinical outcomes of COPD patients. OBJECTIVES: This paper aims to analyze the impact of leisure-time physical activity (LTPA) and daily sitting time (DST) and their interactions on serum vitamin D in patients with COPD. MATERIAL AND METHODS: Participants aged ≥40 years from the National Health and Nutrition Examination Survey (NHANES) in the USA from 2007 to 2012 who had undergone pulmonary function tests and vitamin D tests were selected as the study participants. Participants' LTPA and DST were assessed using the General Practice Assessment Questionnaire (GPAQ). Multivariate logistic regression analysis was used to analyze the relationship between serum vitamin D, LTPA, DSA and the combination of the 2 in patients with COPD, and the results were expressed as odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: This study included 1,448 samples. The mean vitamin D concentration of the samples was (68.27 ±26.78) nmol/L; 360 participants (24.86%) had vitamin D deficiency and 539 participants (37.22%) had vitamin D insufficiency. Vitamin D and 25(OH)D3 expression levels differed across the 4 groups (150 min/week and DST > 8 h revealed the highest vitamin D expression levels, while LTPA 8 h showed the lowest. Vitamin D was weakly correlated with FEV1, FVC, BMI, age, and LTPA (p < 0.01), but not with DST. Body mass index (BMI) was weakly positively correlated with DST (r = 0.142, p < 0.01). CONCLUSIONS: Serum physical activity and DST independently affect vitamin D levels in COPD patients; therefore, increasing physical activity and minimizing DST may help improve vitamin D levels and prevent vitamin D deficiency.

Computational Modeling of Bone Fracture Healing Under Different Initial Conditions and Mechanical Load.

OBJECTIVE: Computational model of bone healing can replace animal experiments to study the parameters affecting the bone healing process, thus reducing the damage to experimental animals and saving a lot of time. We propose a computational model for continuous simulation of four phases of bone healing to study the effects of mechanical environmental and biological factors, including initial conditions at the fracture site, mechanical stimulus loading, and vascular growth rate. METHODS: A finite element model of mechanobiological fracture healing containing several pre-determined variables was developed for bone healing after fracture in sheep, which included many relevant parameters and biological effects during fracture healing, such as the effects of mechanical environment, blood supply level in the local fracture area, cell migration and diffusion, and resorption effects of fracture healing. The effects of several parameters on indices such as Young's modulus of the callus during bone healing were obtained by simulation. RESULTS: The initial geometry of the healing tissue and mechanical loading had the greatest effect on fracture healing, and different preset values were likely to cause delayed or non-healing fractures. Changed initial tissue properties of the healing tissue showed a nonlinear effect on fracture healing rather than a linear delay or advancement. Parameters related to angiogenesis had a greater effect on fracture healing compared to those related to cell migration. CONCLUSION: This paper quantified the effect of fracture healing pre-determined variables on fracture healing to better understand the application of mechanobiology in fracture healing simulation models and optimization of treatment strategies. SIGNIFICANCE: The importance of initial conditions and loads on fracture healing has been shown to help physicians treat bone nonunion or delayed bone healing after a fracture.

The impact of osteoporosis and diabetes on fracture healing under different loading conditions.

BACKGROUND: Osteoporosis and diabetes are two prevalent conditions among the elderly population. Each of these conditions can profoundly influence the fracture healing process by disturbing the associated inflammatory process. However, the combined effects of osteoporosis and diabetes on fracture healing remain unclear. Therefore, the purpose of the present study is to investigate the role of osteoporosis and diabetes in fracture healing and the underlying mechanisms by developing numerical models. METHOD: This study introduces a numerical model that consists of a three-dimensional model of a tibia fracture stabilized by a Locking Compression Plate (LCP), coupled with a two-dimensional axisymmetric model which illustrates the transport and reactions of cells and cytokines throughout the inflammatory phase in early fracture healing. First, the model parameters were calibrated using available experimental data. The model was then implemented to predict the healing outcomes of fractures under five varied conditions, consisting of both osteoporotic and non-osteoporotic bones, each subjected to different physiological loads. RESULTS: The instability of the fracture callus can significantly escalate in osteoporotic fractures (e.g., when a 150 N physiological load is applied, the unstable region of the osteoporotic fracture callus can reach 26 %, in contrast to 12 % in non-osteoporotic fractures). Additionally, the mesenchymal stem cells (MSCs) proliferation and differentiation can be disrupted in osteoporotic fracture compared to non-osteoporotic fractures (e.g., on the 10th day post-fracture, the decrease in the concentration of MSCs, osteoblasts, and chondrocytes in osteoporotic fractures is nearly double that in non-osteoporotic fractures under a 150 N). Finally, the healing process of fractures can suffer significant impairment when osteoporosis coexists with diabetes (e.g., the concentration of MSCs can be drastically reduced by nearly 37 % in osteoporotic fractures under diabetic conditions when subjected to a load of 200 N) CONCLUSIONS: Fracture calluses destabilized by osteoporosis can negatively affect the fracture healing process by disrupting the proliferation and differentiation of mesenchymal stem cells (MSCs). Moreover, when osteoporosis coexists with diabetes, the fracture healing process can severely impair the fracture healing outcomes.

Roux-en-Y Gastric Bypass Improves Insulin Sensitivity in Obese Rats with Type 2 Diabetes Mellitus by Regulating the Grin3a/AMPK Signal Axis in Hypothalamic Arcuate Nucleus.

Objective: The objective of this study was to explore the effects and related mechanisms of Roux-en-Y gastric bypass (RYGB) on insulin sensitivity in obese rats with type 2 diabetes mellitus (T2DM). Methods: The obese T2DM rat model was constructed by feeding a high-fat diet and injecting streptozotocin (STZ), and treated with RYGB. Grin3a shRNA was injected into the bilateral hypothalamic arcuate nucleus (ARC) to knockdown the Grin3a expression on T2DM rats. Eight weeks after operation, the body weight, fasting blood glucose (FBG), fasting serum insulin (FSI), homeostatic model assessment of insulin resistance (HOMA-IR), and plasma triglyceride (TG) levels were assessed. Hematoxylin & eosin (H&E) staining was adopted to observe the white adipose tissue (WAT) of rats. Western blot and qRT-PCR were used to detect the expression of Grin3a, adenosine 5' monophosphate-activated protein kinase (AMPK) and p-AMPK in ARC of rats. Later, the plasmid over-expressing or knocking down Grin3a was transfected into differentiated 3T3-L1 adipocytes, and the TG level and the formation of lipid droplets in adipocyte were assessed by TG kit and oil red O staining. The expression of lipogenic transcription factors in cells was detected by qRT-PCR. Results: RYGB reduced FBG, FSI, HOMA-IR and plasma TG levels in T2DM rats while increasing Grin3a expression and p-AMPK/AMPK ratio in ARC. Knockdown of Grin3a not only reversed the decrease of FBG, FSI, HOMA-IR and plasma TG levels in T2DM rats induced by RYGB, but also reversed the up-regulation of p-AMPK/AMPK ratio in ARC affected by RYGB. Moreover, knocking down Grin3a significantly increased the TG level, promoted the formation of lipid droplets and up-regulated the expressions of lipogenic transcription factors in adipocytes. Conclusion: RYGB improved the insulin sensitivity, reduced the plasma TG level and lessens the fat accumulation in obese T2DM rats by regulating the Grin3a/AMPK signal in ARC.

ceRNA Network Analysis Reveals Potential Key miRNAs and Target Genes in COVID-19-Related Chronic Obstructive Pulmonary Disease.

The continued spread of SARS-CoV-2 has presented unprecedented obstacles to the worldwide public health system. Especially, individuals with chronic obstructive pulmonary disease (COPD) are at a heightened risk of contracting SARS-CoV-2 infection due to their pre-existing respiratory symptoms that are not well-managed. However, the viral mechanism of affecting the expression of host genes, COPD progression, and prognosis is not clear yet.This study integrated the differential expression information of COPD patients and then calculated the correlation between mRNAs and miRNAs to construct a COPD-specific ceRNA network. The DEGs of individuals with SARS-CoV-2 infection and anticipated miRNAs and their targets were analyzed in 9 SARS-CoV-2 sequences from different geographic locations. Furthermore, combining the experimentally validated miRNAs and genes, the regulatory miRNA-mRNA relationships were identified. All the regulatory relationships were integrated into the COPD-specific network and the network modules were explored to get insight into the functional mechanism of SARS-CoV-2 infection in COPD patients.A higher proportion of DEGs compete with the same miRNA suggesting a higher expression of genes in the COPD-specific ceRNA network. Hsa-miR-21-3p is the largest connected point in the network, but the proportion of genes upregulated by hsa-miR-21-3p is low (P = 0.1406). This indicates that the regulatory relationship of competitive inhibition has little effect on has-miR-21, and the high expression pattern is a poor prognostic factor in COPD. Hsa-miR-15a-5p is the most significant miRNA with the highest proportion of DEGs. And ANXA2P3 is the only gene in the COPD ceRNA network that interferes with hsa-miR-15a-5p. In addition, we found that has-miR-1184- and has-miR-99-cored modules were significant, and genes ZDHHC18, PCGF3, and KIAA0319L interacting with them were all associated with COPD prognosis, and high expression of these genes could lead to poor prognosis in COPD.The key regulators such as miR-21, miR-15a, ANXA2P3, ZDHHC18, PCGF3, and KIAA0319L can be used as prognostic biomarkers for early intervention in COPD with SARS-CoV-2 infection.

Depth camera-based model for studying the effects of muscle loading on distal radius fracture healing.

BACKGROUND: Distal radius fractures (DRFs) treated with volar locking plates (VLPs) allows early rehabilitation exercises favourable to fracture recovery. However, the role of rehabilitation exercises induced muscle forces on the biomechanical microenvironment at the fracture site remains to be fully explored. The purpose of this study is to investigate the effects of muscle forces on DRF healing by developing a depth camera-based fracture healing model. METHOD: First, the rehabilitation-related hand motions were captured by a depth camera system. A macro-musculoskeletal model is then developed to analyse the data captured by the system for estimating hand muscle and joint reaction forces which are used as inputs for our previously developed DRF model to predict the tissue differentiation patterns at the fracture site. Finally, the effect of different wrist motions (e.g., from 60° of extension to 60° of flexion) on the DRF healing outcomes will be studied. RESULTS: Muscle and joint reaction forces in hands which are highly dependent on hand motions could significantly affect DRF healing through imposed compressive and bending forces at the fracture site. There is an optimal range of wrist motion (i.e., between 40° of extension and 40° of flexion) which could promote mechanical stimuli governed healing while mitigating the risk of bony non-union due to excessive movement at the fracture site. CONCLUSION: The developed depth camera-based fracture healing model can accurately predict the influence of muscle loading induced by rehabilitation exercises in distal radius fracture healing outcomes. The outcomes from this study could potentially assist osteopathic surgeons in designing effective post-operative rehabilitation strategies for DRF patients.

Effect of uncertain clinical conditions on the early healing and stability of distal radius fractures.

BACKGROUND AND OBJECTIVES: The healing outcomes of distal radius fracture (DRF) treated with the volar locking plate (VLP) depend on surgical strategies and postoperative rehabilitation. However, the accurate prediction of healing outcomes is challenging due to a range of certainties related to the clinical conditions of DRF patients, including fracture geometry, fixation configuration, and physiological loading. The purpose of this study is to investigate the influence of uncertainty and variability in fracture/fixation parameters on the mechano-biology and biomechanical stability of DRF, using a probabilistic numerical approach based on the results from a series of experimental tests performed in this study. METHODS: Six composite radius sawboneses fitted with titanium VLP (VLP 2.0, Austofix) were loaded to failure at a rate of 2 N/s. The testing results of the elastic and plastic behaviour of the VLP were used as inputs for a probabilistic-based computational model of DRF, which simulated mechano-regulated tissue differentiation and fixation elastic capacity at the fracture site. Finally, the probability of success in early indirect healing and fracture stabilisation was predicted. RESULTS: The titanium VLP is a strong and ductile fixation whose flexibility and elastic capacity are governed by flexion working length and bone-to-plate distance, respectively. A fixation with optimised designs and configurations is critical to mechanically stabilising the early fracture site. Importantly, the uncertainty and variability in fracture/fixation parameters could compromise early DRF healing. The physiological loading uncertainty is the most adverse factor, followed by the negative impact of uncertainty in fracture geometry. CONCLUSIONS: The VRP 2.0 fixation made of grade II titanium is a desirable fixation that is strong enough to resist irreparable deformation during early recovery and is also ductile to deform plastically without implant failure at late rehabilitation.

Clinical Guidelines for the Diagnosis and Treatment of Fragility Fractures of the Pelvis.

BACKGROUND: Fragility fractures of the pelvis (FFPs) are osteoporotic pelvic fractures or insufficiency pelvic fractures caused by the low energy injury or stress fracture in daily livings in the elderly more than 60 years, which the incidence is increasing with the aging population in our country. FFPs result in considerable morbidity and mortality and as well as massive financial burden on the already strained health systems throughout the world. METHODS: This clinical guideline was initiated by the Trauma Orthopedic Branch of Chinese Orthopedic Association; the External Fixation and Limb Reconstruction Branch of Chinese Orthopedic Association; the National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation; Senior Department of Orthopedics of Chinese PLA general hospital; the Third Hospital of Hebei Medical University. The grading of recommendations assessment, development and evaluation (GRADE) approach and the reporting items for practice guidelines in healthcare (RIGHT) checklist were adopted. RESULTS: 22 evidence based recommendations were formulated based on 22 most concerned clinical problems among orthopedic surgeons in China. CONCLUSION: Understanding these trends through this guideline will facilitate better clinical care of FFP patients by medical providers and better allocation of resources by policy makers.

Preoperative Virtual Reduction Planning Algorithm of Fractured Pelvis Based on Adaptive Templates.

OBJECTIVE: The minimally invasive treatment of pelvic fractures is one of the most challenging trauma orthopedics surgeries, where preoperative planning is crucial for the performance and outcome of the surgery. However, planning the ideal position of fragments currently relies heavily on the experience of the surgeon. METHODS: A pelvic fracture virtual reduction algorithm for target position is provided based on statistical shape models (SSM). First, according to sexual dimorphism, pelvic SSM based on point cloud curvature down-sampling are constructed as adaptive templates. Then, an optimization algorithm is designed to iteratively adjust the target pose of the fragments and the adaptive matching of the templates. Finally, the feasibility of the method is verified by simulating fractures and clinical data. RESULTS: The pelvis has complex shape characteristics, which can be analyzed by SSM to clearly understand the pattern of change. Experiments showed that the SSM-based pelvic fracture reduction method had translation and rotation errors of 2.20±1.09 mm and 3.16±1.26° in simulated cases, and 2.78±0.95 mm and 3.10±0.53° in clinical cases, which has higher accuracy than methods based on mean shape models, and wider applicability than methods based on pelvic symmetry. CONCLUSION: The pelvic digital model created by SSM has good generalization properties, and the SSM-based virtual reduction algorithm can effectively reconstruct the target position of the fractured pelvis in preoperative planning. SIGNIFICANCE: The proposed reduction method has the characteristics of high precision and wide application range, which provides a powerful tool for the surgeon's virtual preoperative planning.

Advanced surface engineering of titanium materials for biomedical applications: From static modification to dynamic responsive regulation.

Titanium (Ti) and its alloys have been widely used as orthopedic implants, because of their favorable mechanical properties, corrosion resistance and biocompatibility. Despite their significant success in various clinical applications, the probability of failure, degradation and revision is undesirably high, especially for the patients with low bone density, insufficient quantity of bone or osteoporosis, which renders the studies on surface modification of Ti still active to further improve clinical results. It is discerned that surface physicochemical properties directly influence and even control the dynamic interaction that subsequently determines the success or rejection of orthopedic implants. Therefore, it is crucial to endow bulk materials with specific surface properties of high bioactivity that can be performed by surface modification to realize the osseointegration. This article first reviews surface characteristics of Ti materials and various conventional surface modification techniques involving mechanical, physical and chemical treatments based on the formation mechanism of the modified coatings. Such conventional methods are able to improve bioactivity of Ti implants, but the surfaces with static state cannot respond to the dynamic biological cascades from the living cells and tissues. Hence, beyond traditional static design, dynamic responsive avenues are then emerging. The dynamic stimuli sources for surface functionalization can originate from environmental triggers or physiological triggers. In short, this review surveys recent developments in the surface engineering of Ti materials, with a specific emphasis on advances in static to dynamic functionality, which provides perspectives for improving bioactivity and biocompatibility of Ti implants.

Computational Modelling for Managing Pathways to Cartilage Failure.

Over several decades the perception and therefore description of articular cartilage changed substantially. It has transitioned from being described as a relatively inert tissue with limited repair capacity, to a tissue undergoing continuous maintenance and even adaption, through a range of complex regulatory processes. Even from the narrower lens of biomechanics, the engagement with articular cartilage has changed from it being an interesting, slippery material found in the hostile mechanical environment between opposing long bones, to an intriguing example of mechanobiology in action. The progress revealing this complexity, where physics, chemistry, material science and biology are merging, has been described with increasingly sophisticated computational models. Here we describe how these computational models of cartilage as an integrated system can be combined with the approach of structural reliability analysis. That is, causal, deterministic models placed in the framework of the probabilistic approach of structural reliability analysis could be used to understand, predict, and mitigate the risk of cartilage failure or pathology. At the heart of this approach is seeing cartilage overuse and disease processes as a 'material failure', resulting in failure to perform its function, which is largely mechanical. One can then describe pathways to failure, for example, how homeostatic repair processes can be overwhelmed leading to a compromised tissue. To illustrate this 'pathways to failure' approach, we use the interplay between cartilage consolidation and lubrication to analyse the increase in expected wear rates associated with cartilage defects or meniscectomy.

Development of numerical model-based machine learning algorithms for different healing stages of distal radius fracture healing.

BACKGROUND AND OBJECTIVES: Early therapeutic exercises are vital for the healing of distal radius fractures (DRFs) treated with the volar locking plate. However, current development of rehabilitation plans using computational simulation is normally time-consuming and requires high computational power. Thus, there is a clear need for developing machine learning (ML) based algorithms that are easy for end-users to implement in daily clinical practice. The purpose of the present study is to develop optimal ML algorithms for designing effective DRF physiotherapy programs at different stages of healing. METHOD: First, a three-dimensional computational model for the healing of DRF was developed by integrating mechano-regulated cell differentiation, tissue formation and angiogenesis. The model is capable of predicting time-dependant healing outcomes based on different physiologically relevant loading conditions, fracture geometries, gap sizes, and healing time. After being validated using available clinical data, the developed computational model was implemented to generate a total of 3600 clinical data for training the ML models. Finally, the optimal ML algorithm for each healing stage was identified. RESULTS: The selection of the optimal ML algorithm depends on the healing stage. The results from this study show that cubic support vector machine (SVM) has the best performance in predicting the healing outcomes at the early stage of healing, while trilayered ANN outperforms other ML algorithms in the late stage of healing. The outcomes from the developed optimal ML algorithms indicate that Smith fractures with medium gap sizes could enhance the healing of DRF by inducing larger cartilaginous callus, while Colles fractures with large gap sizes may lead to delayed healing by bringing excessive fibrous tissues. CONCLUSIONS: ML represents a promising approach for developing efficient and effective patient-specific rehabilitation strategies. However, ML algorithms at different healing stages need to be carefully chosen before being implemented in clinical applications.

Semi-XctNet: Volumetric images reconstruction network from a single projection image via semi-supervised learning.

Deep learning networks have achieved remarkable progress in various tasks of medical imaging. Most of the recent success in computer vision highly depend on large amounts of carefully annotated data, whereas labelling is arduous, time-consuming and in need of expertise. In this paper, a semi-supervised learning method, Semi-XctNet, is proposed for volumetric images reconstruction from a single X-ray image. In our framework, the effect of regularization on pixel-level prediction is enhanced by introducing a transformation consistent strategy into the model. Furthermore, a multi-stage training strategy is designed to ameliorate the generalization performance of the teacher network. An assistant module is also introduced to improve the pixel quality of pseudo-labels, thereby further improving the reconstruction accuracy of the semi-supervised model. The semi-supervised method proposed in this paper has been extensively validated on the LIDC-IDRI lung cancer detection public data set. Quantitative results show that SSIM (structural similarity measurement) and PSNR (peak signal noise ratio) are 0.8384 and 28.7344 respectively. Compared with the state-of-the-arts, Semi-XctNet exhibits excellent reconstruction performance, thus demonstrating the effectiveness of our method on the task of volumetric images reconstruction network from a single X-ray image.

Synchronized activity of sensory neurons initiates cortical synchrony in a model of neuropathic pain.

Increased low frequency cortical oscillations are observed in people with neuropathic pain, but the cause of such elevated cortical oscillations and their impact on pain development remain unclear. By imaging neuronal activity in a spared nerve injury (SNI) mouse model of neuropathic pain, we show that neurons in dorsal root ganglia (DRG) and somatosensory cortex (S1) exhibit synchronized activity after peripheral nerve injury. Notably, synchronized activity of DRG neurons occurs within hours after injury and 1-2 days before increased cortical oscillations. This DRG synchrony is initiated by axotomized neurons and mediated by local purinergic signaling at the site of nerve injury. We further show that synchronized DRG activity after SNI is responsible for increasing low frequency cortical oscillations and synaptic remodeling in S1, as well as for inducing animals' pain-like behaviors. In naive mice, enhancing the synchrony, not the level, of DRG neuronal activity causes synaptic changes in S1 and pain-like behaviors similar to SNI mice. Taken together, these results reveal the critical role of synchronized DRG neuronal activity in increasing cortical plasticity and oscillations in a neuropathic pain model. These findings also suggest the potential importance of detection and suppression of elevated cortical oscillations in neuropathic pain states.

Osteochondral junction leakage and cartilage joint lubrication.

BACKGROUND AND OBJECTIVES: Previous studies have shown that there is potentially interstitial fluid exchange between cartilage tissue and the subarticular spongiosa region in the case of injury or disease (e.g., osteoarthritis and osteoporosis). Interstitial flow is also required for cartilage lubrication under joint load. A key question then is how cartilage lubrication is modified by increased interstitial fluid leakage across the osteochondral junction. Thus, the purpose of this study is to develop a numerical model to investigate changes in cartilage lubrication with changes in osteochondral junction leakage. METHODS: The multi-phase coupled model includes domains corresponding to the contact gap, cartilage tissue and subchondral bone plate region (ScBP). Each of these domains are treated as poroelastic systems, with their coupling implemented through mass and pressure continuity. The effects of osteochondral junction leakage on lubrication were investigated with a parametric study on the relative permeability between the ScBP and cartilage tissue. RESULTS: Significant effects of ScBP permeability were predicted, especially during the early stage of the junction leakage development (early stage of the disease). There is a significant reduction in mixed-mode lubrication duration under the effect of increased junction leakage (the cartilage tissue mixed-mode lubrication duration is about 33% decrease for a relative permeability ratio of 0.1 between ScBP and cartilage tissue, and about 52% decrease under the osteoarthritis condition). In addition, the time for cartilage to reach steady-state consolidation is significantly reduced when ScBP permeability increases (the consolidation time reduces from roughly 2 h to 1.2 h when the relative permeability ratio increases from 0.001 to 0.1, and it reduces to 0.8 h for an advanced osteoarthritis condition). It is predicted that the initial friction coefficient could increase by over 60% when the ScBP permeability is consistent with an advanced osteoarthritis (OA) condition. CONCLUSION: Increased osteochondral junction leakage induced by joint injury and disease could result in increased cartilage surface wear rates due to more rapid interstitial fluid depressurization within articular cartilage.

Spinopelvic dissociation: extended definition, physical examination, classification, and therapy.

BACKGROUND: Spinopelvic dissociation (SPD) is generally caused by high-energy injury mechanisms, and, in the absence of timely diagnosis and treatment, it can lead to chronic pain and progressive deformity. However, SPD is difficult to manage because of its rarity and complexity. In this study, we re-defined SPD according to the mechanism of injuries and biomechanical characteristics of the posterior pelvic ring and developed new classification criteria and treatment principles based on the classification for SPD. METHODS: Between June 2015 and September 2020, 30 patients with SPD which were selected from 138 patients with pelvic fractures were enrolled. Physical examination was performed, classification criteria (301 SPD classification) were developed, and specific treatment standards were established according to the classifications. RESULTS: The injury mechanisms and co-existing injuries did not significantly differ between the classical SPD patients and expanded SPD patients. The 301 SPD classification criteria covered all the patients. Fixation by biplanar penetration screws was used in 7 patients, 11 patients received fixation by uniplanar penetration screws, 6 patients used sacroiliac compression screws, 3 patients received uniplanar screws combined with sacroiliac compression screws, and open spondylopelvic fixation was used in only 3 patients. According to the Matta criteria, 19, 7, and 4 patients achieved excellent, good, and fair reduction. The Majeed function score of the patients ranged from 9 to 96 points, and the mean score was 72.9 ± 24.6 points. CONCLUSION: The expanded definition for SPD is particularly significant for definite diagnosis and prevention of missing diagnosis, based on which the 301SPD classification criteria can more systemically guide the clinical treatment of SPD, increase the treatment efficacy, and reduce surgical trauma. Chinese Clinical Trial Registry: ChiCTR-IPR-16009340.