Engineering stem cells to produce exosomes with enhanced bone regeneration effects: an alternative strategy for gene therapy.

BACKGROUND: Exosomes derived from stem cells have been widely studied for promoting regeneration and reconstruction of multiple tissues as "cell-free" therapies. However, the applications of exosomes have been hindered by limited sources and insufficient therapeutic potency. RESULTS: In this study, a stem cell-mediated gene therapy strategy is developed in which mediator mesenchymal stem cells are genetically engineered by bone morphogenetic protein-2 gene to produce exosomes (MSC-BMP2-Exo) with enhanced bone regeneration potency. This effect is attributed to the synergistic effect of the content derived from MSCs and the up-regulated BMP2 gene expression. The MSC-BMP2-Exo also present homing ability to the injured site. The toxic effect of genetical transfection vehicles is borne by mediator MSCs, while the produced exosomes exhibit excellent biocompatibility. In addition, by plasmid tracking, it is interesting to find a portion of plasmid DNA can be encapsulated by exosomes and delivered to recipient cells. CONCLUSIONS: In this strategy, engineered MSCs function as cellular factories, which effectively produce exosomes with designed and enhanced therapeutic effects. The accelerating effect in bone healing and the good biocompatibility suggest the potential clinical application of this strategy.

A novel surgical planning system using an AI model to optimize planning of pedicle screw trajectories with highest bone mineral density and strongest pull-out force.

OBJECTIVE: The purpose of this study was to evaluate the ability of a novel artificial intelligence (AI) model in identifying optimized transpedicular screw trajectories with higher bone mineral density (BMD) as well as higher pull-out force (POF) in osteoporotic patients. METHODS: An innovative pedicle screw trajectory planning system called Bone's Trajectory was developed using a 3D graphic search and an AI-based finite element analysis model. The preoperative CT scans of 21 elderly osteoporotic patients were analyzed retrospectively. The AI model automatically calculated the number of alternative transpedicular trajectories, the trajectory BMD, and the estimated POF of L3-5. The highest BMD and highest POF of optimized trajectories were recorded and compared with AO standard trajectories. RESULTS: The average patient age and average BMD of the vertebral bodies were 69.6 ± 7.8 years and 55.9 ± 17.1 mg/ml, respectively. On both sides of L3-5, the optimized trajectories showed significantly higher BMD and POF than the AO standard trajectories (p < 0.05). On average, the POF of optimized trajectory screws showed at least a 2.0-fold increase compared with AO trajectory screws. CONCLUSIONS: The novel AI model performs well in enabling the selection of optimized transpedicular trajectories with higher BMD and POF than the AO standard trajectories.

Multifunctional Nanoengineered Hydrogels Consisting of Black Phosphorus Nanosheets Upregulate Bone Formation.

Tissue-engineered hydrogels have received extensive attention as their mechanical properties, chemical compositions, and biological signals can be dynamically modified for mimicking extracellular matrices (ECM). Herein, the synthesis of novel double network (DN) hydrogels with tunable mechanical properties using combinatorial screening methods is reported. Furthermore, nanoengineered (NE) hydrogels are constructed by addition of ultrathin 2D black phosphorus (BP) nanosheets to the DN hydrogels with multiple functions for mimicking the ECM microenvironment to induce tissue regeneration. Notably, it is found that the BP nanosheets exhibit intrinsic properties for induced CaP crystal particle formation and therefore improve the mineralization ability of NE hydrogels. Finally, in vitro and in vivo data demonstrate that the BP nanosheets, mineralized CaP crystal nanoparticles, and excellent mechanical properties provide a favorable ECM microenvironment to mediate greater osteogenic cell differentiation and bone regeneration. Consequently, the combination of bioactive chemical materials and excellent mechanical stimuli of NE hydrogels inspire novel engineering strategies for bone-tissue regeneration.

Matrix metallopeptidase 9 targeted by hsa-miR-494 promotes silybin-inhibited osteosarcoma.

Osteosarcoma (OS) is the most common malignant tumor that develops in bone. Its mortality is very high. Therefore, study of mechanisms of pathogenesis of the OS is urgently required. Previous studies of microarray showed that the expression levels of matrix metallopeptidase 9 (MMP-9) altered significantly in OS. In addition, overexpression of MMP-9 is recognized as an indicator in cancer. However, the exact roles of MMP-9 in OS are not fully investigated. Thus, we firstly studied the roles of MMP-9 in OS and revealed that silence of MMP-9 inhibited OS cell proliferation as determined by MTT assay and colony formation assay. Secondly, we conducted TUNEL assay and confirmed loss of functions of MMP-9 induced OS cell apoptosis. Next, we used lentivector packaging method to overexpress MMP-9 and found that overexpression of MMP-9 promoted OS cell migration. Fourthly, the results of luciferase assay showed that MMP-9 was targeted by hsa-miR-494, which inhibited OS. Fifthly, we revealed that the levels of hsa-miR-494 were upregulated by the drug silybin which inhibited OS. Finally, we revealed that silybin inhibited OS cell viability by altering the protein levels of ß-catenin and Runt-related transcription factor 2 (RUNX2) as determined by western blot and immunocytochemistry (ICC).

Aging Reduces an ERRalpha-Directed Mitochondrial Glutaminase Expression Suppressing Glutamine Anaplerosis and Osteogenic Differentiation of Mesenchymal Stem Cells.

Aging deteriorates osteogenic capacity of mesenchymal stem/stromal cells (MSCs), contributing to imbalanced bone remodeling and osteoporosis. Glutaminase (Gls) catabolizes glutamine into glutamate at the first step of mitochondrial glutamine (Gln)-dependent anaplerosis which is essential for MSCs upon osteogenic differentiation. Estrogen-related receptor α (ERRα) regulates genes required for mitochondrial function. Here, we found that ERRα and Gls are upregulated by osteogenic induction in human MSCs (hMSCs). In contrast, osteogenic differentiation capacity and glutamine consumption of MSCs, as well as ERRα, Gls and osteogenic marker genes are significantly reduced with age. We demonstrated that ERRα binds to response elements on Gls promoter and affects glutamine anaplerosis through transcriptional induction of Gls. Conversely, mTOR inhibitor rapamycin, ERRα inverse agonist compound 29 or Gls inhibitor BPTES leads to reduced Gln anaplerosis and deteriorated osteogenic differentiation of hMSCs. Importantly, overexpression of ERRα or Gls restored impairment by these inhibitors. Finally, we proved that compensated ERRα or Gls expression indeed potentiated Gln anaplerosis and osteogenic capability of elderly mice MSCs in vitro. Together, we establish that Gls is a novel ERRα target gene and ERRα/Gls signaling pathway plays an important role in osteogenic differentiation of MSCs, providing new sights into novel regenerative therapeutics development. Our findings suggest that restoring age-related mitochondrial Gln-dependent anaplerosis may be beneficial for degenerative bone disorders such as osteoporosis. Stem Cells 2017;35:411-424.

Lumbar intervertebral disc allograft transplantation: the revascularisation pattern.

PURPOSE: Fresh frozen intervertebral disc allograft transplantation has been reported to be a viable treatment option for advanced degenerative disc diseases, but rapid degeneration of the postoperative allograft was found. Loss of nutrient supply is believed to be the most likely inducer because the disc allografts have to endure in an ischaemic environment until the nutrient pathway is re-established. The aim of this study was to focus on the revascularisation of the disc allograft after transplantation in goats. METHODS: Twenty male goats were used in this study. Intervertebral disc allograft transplantation was performed at L4/L5. Groups of five goats were killed at 1.5, 6 and 12 m postoperatively, respectively. The transplanted segments were harvested, fixed, sagittally cut and decalcified for H&E staining and immunochemistry to observe the blood vessel formation at the endplates, anterior outer annulus, posterior outer annulus, inner annulus and the nucleus. The blood vessel density and the sectional vessel area were measured. RESULTS: Blood vessels were first found in the marrow space of the bony endplate and the outer annulus at 1.5 month postoperatively. Then, they were able to penetrate to reach the cartilaginous endplate and the inner annulus after 6 months. Interestingly, the endplate area possessed the most abundant blood vessels, with the highest level of vessel density and area at the final follow-up. None of these newly formed vessels invaded the nucleus during the observation period. CONCLUSIONS: Revascularisation of the postoperative disc allograft has been determined, but its pattern was different from that in adult normal discs, suggesting that the typical nutrient diffusion pattern may be affected after transplantation.

Lumbar intervertebral disc allograft transplantation: long-term mobility and impact on the adjacent segments.

PURPOSE: Fresh-frozen intervertebral disc (IVD) allograft transplantation has been successfully performed in the human cervical spine. Whether this non-fusion technology could truly decrease adjacent segment disease is still unknown. This study evaluated the long-term mobility of the IVD-transplanted segment and the impact on the adjacent spinal segments in a goat model. METHODS: Twelve goats were used. IVD allograft transplantation was performed at lumbar L4/L5 in 5 goats; the other 7 goats were used as the untreated control (5) and for the supply of allografts (2). Post-operation lateral radiographs of the lumbar spine in the neutral, full-flexion and full-extension positions were taken at 1, 3, 6, 9 and 12 months. Disc height (DH) of the allograft and the adjacent levels was calculated and range of motion (ROM) was measured using the Cobb's method. The anatomy of the adjacent discs was observed histologically. RESULTS: DH of the transplanted segment was decreased significantly after 3 months but no further reduction was recorded until the final follow-up. No obvious alteration was seen in the ROM of the transplanted segment at different time points with the ROM at 12 months being comparable to that of the untreated control. The DH and ROM in the adjacent segments were well maintained during the whole observation period. At post-operative 12 months, the ROM of the adjacent levels was similar to that of the untreated control and the anatomical morphology was well preserved. CONCLUSIONS: Lumbar IVD allograft transplantation in goats could restore the segmental mobility and did not negatively affect the adjacent segments after 12 months.

MiR-9-5p, miR-675-5p and miR-138-5p Damages the Strontium and LRP5-Mediated Skeletal Cell Proliferation, Differentiation, and Adhesion.

This study was designed to evaluate the effects of strontium on the expression levels of microRNAs (miRNAs) and to explore their effects on skeletal cell proliferation, differentiation, adhesion, and apoptosis. The targets of these miRNAs were also studied. Molecular cloning, cell proliferation assay, cell apoptosis assay, quantitative real-time PCR, and luciferase reporter assay were used. Strontium altered the expression levels of miRNAs in vitro and in vivo. miR-9-5p, miR-675-5p, and miR-138-5p impaired skeletal cell proliferation, cell differentiation and cell adhesion. miR-9-5p and miR-675-5p induced MC3T3-E1 cell apoptosis more specifically than miR-138-5p. miR-9-5p, miR-675-5p, and miR-138-5p targeted glycogen synthase kinase 3 ß (GSK3ß), ATPase Aminophospholipid Transporter Class I Type 8A Member 2 (ATP8A2), and Eukaryotic Translation Initiation Factor 4E Binding Protein 1 (EIF4EBP1), respectively. Low-density lipoprotein receptor-related protein 5 (LRP5) played a positive role in skeletal development. miR-9-5p, miR-675-5p, and miR-138-5p damage strontium and LRP5-mediated skeletal cell proliferation, differentiation, and adhesion, and induce cell apoptosis by targeting GSK3ß, ATP8A2, and EIF4EBP1, respectively.

Mesenchymal stem cells reduce intervertebral disc fibrosis and facilitate repair.

Intervertebral disc degeneration is associated with back pain and radiculopathy which, being a leading cause of disability, seriously affects the quality of life and presents a hefty burden to society. There is no effective intervention for the disease and the etiology remains unclear. Here, we show that disc degeneration exhibits features of fibrosis in humans and confirmed this in a puncture-induced disc degeneration (PDD) model in rabbit. Implantation of bone marrow-derived mesenchymal stem cells (MSCs) to PDD discs can inhibit fibrosis in the nucleus pulposus with effective preservation of mechanical properties and overall spinal function. We showed that the presence of MSCs can suppress abnormal deposition of collagen I in the nucleus pulposus, modulating profibrotic mediators MMP12 and HSP47, thus reducing collagen aggregation and maintaining proper fibrillar properties and function. As collagen fibrils can regulate progenitor cell activities, our finding provides new insight to the limited self-repair capability of the intervertebral disc and importantly the mechanism by which MSCs may potentiate tissue regeneration through regulating collagen fibrillogenesis in the context of fibrotic diseases.

Pyroptosis in Osteoarthritis: Molecular Mechanisms and Therapeutic Implications.

Osteoarthritis (OA) is a chronic disease that causes pain and functional impairment by affecting joint tissue. Its global impact is noteworthy, causing significant economic losses and property damage. Despite extensive research, the underlying pathogenesis of OA remain an area of ongoing investigation. It has recently been discovered that the OA progression is significantly influenced by pyroptosis. Pyroptosis is a complex process that involves three pathways culminating in the assembly of Gasdermin-D (GSDMD)-N-terminal (GSDMD-NT) into pores through aggregation on the plasma membrane. The aggregation of GSDMD-NT proteins stimulates the release of inflammatory mediators, such as Interleukin-1ß (IL-1ß), Interleukin-18 (IL-18), and Matrix Metallopeptidase 13 (MMP13), ultimately leading to cellular lysis. The pyroptosis process in specific cells, including synovial macrophages, fibroblast-like synoviocytes (FLS), chondrocytes, and subchondral osteoblasts, contributs factor to the development of OA. Currently, the specific cells that undergo pyroptosis first are not yet fully understood, and it remains unknown whether pyroptosis in one cell can trigger the same process in other cells. Therefore, targeting pyroptosis could potentially offer a novel treatment approach for OA patients. We present a comprehensive analysis of the molecular mechanisms and key features of pyroptosis. We also outline the current research progress on various aspects, including synovial tissue, articular cartilage, extracellular matrix (ECM), and subchondral bone, with a focus on pyroptosis. The aim is to provide theoretical references for the effective management of OA.

Signalling interaction between ß-catenin and other signalling molecules during osteoarthritis development.

Osteoarthritis (OA) is the most prevalent disorder of synovial joint affecting multiple joints. In the past decade, we have witnessed conceptual switch of OA pathogenesis from a 'wear and tear' disease to a disease affecting entire joint. Extensive studies have been conducted to understand the underlying mechanisms of OA using genetic mouse models and ex vivo joint tissues derived from individuals with OA. These studies revealed that multiple signalling pathways are involved in OA development, including the canonical Wnt/ß-catenin signalling and its interaction with other signalling pathways, such as transforming growth factor ß (TGF-ß), bone morphogenic protein (BMP), Indian Hedgehog (Ihh), nuclear factor κB (NF-κB), fibroblast growth factor (FGF), and Notch. The identification of signalling interaction and underlying mechanisms are currently underway and the specific molecule(s) and key signalling pathway(s) playing a decisive role in OA development need to be evaluated. This review will focus on recent progresses in understanding of the critical role of Wnt/ß-catenin signalling in OA pathogenesis and interaction of ß-catenin with other pathways, such as TGF-ß, BMP, Notch, Ihh, NF-κB, and FGF. Understanding of these novel insights into the interaction of ß-catenin with other pathways and its integration into a complex gene regulatory network during OA development will help us identify the key signalling pathway of OA pathogenesis leading to the discovery of novel therapeutic strategies for OA intervention.

Finite element analysis of a new preoperative traction for cervical kyphosis: suspensory traction.

A finite element model of cervical kyphosis was established to analyze the stress of cervical spine under suspensory traction and to explore the mechanism and effect of it. A patient with typical cervical kyphosis (C2-C5) underwent CT scan imaging, and 3D slicer was used to reconstruct the C2 to T2 vertebral bodies. The reconstructed data was imported into Hypermesh 2020 and Abaqus 2017 for meshing and finite element analysis. The changes of the kyphotic angle and the von Mises stress on the annulus fibrosus of each intervertebral disc and ligaments were analyzed under suspensory traction conditions. With the increase of suspensory traction weight, the overall kyphosis of cervical spine showed a decreasing trend. The correction of kyphosis was mainly contributed by the change of kyphotic segments. The kyphotic angle of C2-C5 was corrected from 45° to 13° finally. In cervical intervertebral discs, the stress was concentrated to anterior and posterior part, except for C4-5. The stress of the anterior longitudinal ligament (ALL) decreased from the rostral to the caudal, and the high level von Mises stress of the kyphotic segments appeared at C2-C3, C3-C4, and C4-C5. The roles of the other ligaments were not obvious. The kyphotic angle was significantly reduced by the suspensory traction. Shear effect due to the high von Mises stress in the anterior and posterior parts of annulus fibrosus and the tension on the anterior longitudinal ligament play a role in the correction of cervical kyphosis.

A highly stretchable smart dressing for wound infection monitoring and treatment.

Smart dressings integrated with bioelectronics have attracted considerable attention and become promising solutions for skin wound management. However, due to the mechanical distinction between human body and the interface of electronics, previous smart dressings often suffered obvious degradation in electrical performance when attached to the soft and curvilinear wound sites. Here, we report a stretchable dressing integrated with temperature and pH sensor for wound status monitoring, as well as an electrically controlled drug delivery system for infection treatment. The wound dressing was featured with the deployment of liquid metal for seamless connection between rigid electrical components and gold particle-based electrodes, achieving a stretchable soft-hard interface. Stretching tests showed that both the sensing system and drug delivery system exhibited good stretchability and long-term stable conductivity with the resistance change rate less than 6 % under 50 % strain. Animal experiments demonstrated that the smart dressing was capable of detecting bacterial infection via the biomarkers of temperature and pH value and the infection factors of wound were significantly improved with therapy through electrically controlled antibiotics releasing. This proof-of-concept prototype has potential to significantly improve management of the wound, especially those with dynamic strain.

Tibial Cortex Transverse Transport Facilitates Severe Diabetic Foot Wound Healing via HIF-1α-Induced Angiogenesis.

Purpose: Management of severe diabetic foot ulcers (DFUs) remains challenging. Tibial cortex transverse transport (TTT) facilitates healing and limb salvage in patients with recalcitrant DFUs. However, the underlying mechanism is largely unknown, necessitating the establishment of an animal model and mechanism exploration. Methods: Severe DFUs were induced in rats, then assigned to TTT, sham, or control groups (n=16/group). The TTT group underwent a tibial corticotomy, with 6 days each of medial and lateral transport; the sham group had a corticotomy without transport. Ulcer healing was assessed through Laser Doppler, CT angiography, histology, and immunohistochemistry. Serum HIF-1α, PDGF-BB, SDF-1, and VEGF levels were measured by ELISA. Results: The TTT group showed lower percentages of wound area, higher dermis thickness (all p < 0.001 expect for p = 0.001 for TTT vs Sham at day 6) and percentage of collagen content (all p < 0.001) than the other two groups. The TTT group had higher perfusion and vessel volume in the hindlimb (all p < 0.001). The number of CD31+ cells (all p < 0.001) and VEGFR2+ cells (at day 6, TTT vs Control, p = 0.001, TTT vs Sham, p = 0.006; at day 12, TTT vs Control, p = 0.003, TTT vs Sham, p = 0.01) were higher in the TTT group. The activity of HIF-1α, PDGF-BB, and SDF-1 was increased in the TTT group (all p < 0.001 except for SDF-1 at day 12, TTT vs Sham, p = 0.005). The TTT group had higher levels of HIF-1α, PDGF-BB, SDF-1, and VEGF in serum than the other groups (all p < 0.001). Conclusion: TTT enhanced neovascularization and perfusion at the hindlimb and accelerated healing of the severe DFUs. The underlying mechanism is related to HIF-1α-induced angiogenesis.

miR-204 ameliorates osteoarthritis pain by inhibiting SP1-LRP1 signaling and blocking neuro-cartilage interaction.

Osteoarthritis (OA) is a painful degenerative joint disease and is the leading cause of chronic disability among elderly individuals. To improve the quality of life for patients with OA, the primary goal for OA treatment is to relieve the pain. During OA progression, nerve ingrowth was observed in synovial tissue and articular cartilage. These abnormal neonatal nerves act as nociceptors to detect OA pain signals. The molecular mechanisms for transmitting OA pain in the joint tissues to the central nerve system (CNS) is currently unknown. MicroRNA miR-204 has been demonstrated to maintain the homeostasis of joint tissues and have chondro-protective effect on OA pathogenesis. However, the role of miR-204 in OA pain has not been determined. In this study, we investigated interactions between chondrocytes and neural cells and evaluated the effect and mechanism of miR-204 delivered by exosome in the treatment of OA pain in an experimental OA mouse model. Our findings demonstrated that miR-204 could protect OA pain by inhibition of SP1- LDL Receptor Related Protein 1 (LRP1) signaling and blocking neuro-cartilage interaction in the joint. Our studies defined novel molecular targets for the treatment of OA pain.

Risk of metabolic abnormalities in osteoarthritis: a new perspective to understand its pathological mechanisms.

Although aging has traditionally been viewed as the most important risk factor for osteoarthritis (OA), an increasing amount of epidemiological evidence has highlighted the association between metabolic abnormalities and OA, particularly in younger individuals. Metabolic abnormalities, such as obesity and type II diabetes, are strongly linked to OA, and they affect both weight-bearing and non-weight-bearing joints, thus suggesting that the pathogenesis of OA is more complicated than the mechanical stress induced by overweight. This review aims to explore the recent advances in research on the relationship between metabolic abnormalities and OA risk, including the impact of abnormal glucose and lipid metabolism, the potential pathogenesis and targeted therapeutic strategies.

Cartilage organoids and osteoarthritis research: a narrative review.

Osteoarthritis (OA) is one of the most common degenerative joint diseases, significantly impacting individuals and society. With the acceleration of global aging, the incidence of OA is increasing. The pathogenesis of osteoarthritis is not fully understood, and there is no effective way to alleviate the progression of osteoarthritis. Therefore, it is necessary to develop new disease models and seek new treatments for OA. Cartilage organoids are three-dimensional tissue masses that can simulate organ structure and physiological function and play an important role in disease modeling, drug screening, and regenerative medicine. This review will briefly analyze the research progress of OA, focusing on the construction and current development of cartilage organoids, and then describe the application of cartilage organoids in OA modeling, drug screening, and regeneration and repair of cartilage and bone defects. Finally, some challenges and prospects in the development of cartilaginous organoids are discussed.

Focal osteoporosis defect is associated with vertebral compression fracture prevalence in a bone mineral density-independent manner.

Introduction: Focal osteoporosis defect has shown a high association with the bone fragility and osteoporotic fracture prevalence. However, no routine computed tomography (CT)-based vertebral focal osteoporosis defect measurement and its association with vertebral compression fracture (VCF) were discussed yet. This study aimed to develop a routine CT-based measurement method for focal osteoporosis defect quantification, and to assess its association with the VCF prevalence. Materials and Methods: A total of 205 cases who underwent routine CT scanning, were retrospectively reviewed and enrolled into either the VCF or the control group. The focal bone mineral content loss (focal BMC loss), measured as the cumulated demineralization within bone void space, was proposed for focal osteoporosis defect quantification. Its scan-rescan reproducibility and its correlation with trabecular bone mineral density (BMD) and apparent microarchitecture parameters were evaluated. The association between focal BMC loss and the prevalence of VCF was studied by logistic regression. Results: The measurement of focal BMC loss showed high reproducibility (RMSSD = 0.011 mm, LSC = 0.030 mm, ICC = 0.97), and good correlation with focal bone volume fraction (r = 0.79, P < 0.001), trabecular bone separation (r = 0.76, P < 0.001), but poor correlation with trabecular BMD (r = 0.37, P < 0.001). The focal BMC loss was significantly higher in the fracture group than the control (1.03 ± 0.13 vs. 0.93 ± 0.11 mm; P < 0.001), and was associated with prevalent VCF (1.87, 95% CI = 1.31-2.65, P < 0.001) independent of trabecular BMD level. Discussion: As a surrogate measure of focal osteoporosis defect, focal BMC Loss independently associated with the VCF prevalence. It suggests that focal osteoporosis defect is a common manifestation that positively contributed to compression fracture risk and can be quantified with routine CT using focal BMC Loss.

Are mindfulness treatments effective for pain in cancer patients? A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Mindfulness-based interventions (MBIs) have been recently applied in pain management and cancer care. However, inconsistencies exist concerning the effectiveness of MBIs on pain control among cancer patients. Therefore, this study aimed to examine the efficacy of MBIs on pain in cancer patients via a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: Databases (MEDLINE, PubMed, Embase, CINAHL, PsycINFO, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov) were searched using key terms related to pain, cancer and mindfulness. The primary outcome was pain intensity. Standardized mean difference (SMD) of each outcome with 95% confidence interval (95% CI) was calculated. The quality of evidence was assessed by GRADE assessment. RESULTS: Ten RCTs with 843 participants were included. Significant pooled effects of MBIs on pain intensity were found at both short-term (SMD = -0.19, 95% CI [-0.33 to -0.04]) and long-term (SMD = -0.20, 95% CI [-0.35 to -0.05]) follow-up, whereas no significance was observed for pain interference. In subgroup analyses, significant intervention effects were only seen in clinic-based MBIs compared to remote MBIs, and pooled effects of MBIs in attenuating pain were discovered relative to passive rather than active comparators. GRADE ratings showed moderate certainty of evidence in MBIs for pain intensity but low for pain interference. CONCLUSIONS: The efficacy of MBIs in reducing pain intensity among cancer patients was revealed in this meta-analysis, albeit with a small effect size. Future research is warranted to optimize mindfulness treatment for pain control in cancer patients with high methodological quality and a large sample size. SIGNIFICANCE: The effect of MBIs on pain in cancer patients was demonstrated in our analysis, albeit with small effect sizes. High-quality RCTs are needed to verify the efficacy of MBIs on cancer patients or survivors with pain complaints. Future trials should take into account the specific pain outcome measures (pain intensity or pain interference), the approach of intervention provision (clinic-based or remote MBI, group or individual practice), the duration and frequency of interventions and the comparators (passive or active control arms).

Patient-specific numerical investigation of the correction of cervical kyphotic deformity based on a retrospective clinical case.

Little research has been reported on evaluating the safety of the fixation construct in cervical kyphosis correction. In this study, we proposed a principal-strain criterion to evaluate the safety of the fixation construct and validated the modeling method against a retrospective case of anterior cervical discectomy fusion (ACDF). From C2 to T2 vertebra bodies, fixation instruments were reconstructed and positioned as per postoperative computed tomography (CT) scans. Head weight (HW) and various moments estimated from isometric strength data were imposed onto the C2. The postoperative stability of non-surgical segments, deformations surrounding the screw trajectories, and contact slipping on zygapophysial joints were analyzed. The model was validated against the reality that the patient had a good fusion and deformity correction. The ACDF restricted the range of motions (ROMs) of cervical segments and lent stability to vertebra fusion, no failure was found in the finite element (FE) model of cervical vertebrae. The deformation surrounding the screw trajectories were concentrated to the lateral sides of trajectories, recommending that the shape of the anterior cervical plate conforming to the curvature of the vertebra and screws fully inserted into vertebrae reduced the deformation concentration around the screw trajectories.