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STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate the effectiveness of pedicle screw trajectory planning based on artificial intelligence (AI) software in patients with different levels of bone mineral density (BMD). SUMMARY OF BACKGROUND DATA: AI-based pedicle screw trajectory planning has potential to improve pullout force (POF) of screws. However, there is currently no literature investigating the efficacy of AI-based pedicle screw trajectory planning in patients with different levels of BMD. METHODS: The patients were divided into 5 groups (group A-E) according to their BMD. The AI software utilizes lumbar spine CT data to perform screw trajectory planning and simulate AO screw trajectories for bilateral L3-5 vertebral bodies. Both screw trajectories were subdivided into unicortical and bicortical modes. The AI software automatically calculating the POF and pullout risk of every screw trajectory. The POF and risk of screw pullout for AI-planned screw trajectories and AO standard trajectories were compared and analyzed. RESULTS: Forty-three patients were included. For the screw sizes, AI-planned screws were greater in diameter and length than those of AO screws (P<0.05). In groups B-E, the AI unicortical trajectories had a POF of over 200N higher than that of AO unicortical trajectories. POF was higher in all groups for the AI bicortical screw trajectories compared with the AO bicortical screw trajectories (P<0.05). AI unicortical trajectories in groups B-E had a lower risk of screw pullout compared with that of AO unicortical trajectories (P<0.05). CONCLUSIONS: AI unicortical screw trajectory planning for lumbar surgery in patients with BMD of 40-120 mg/cm3 can significantly improve screw POF and reduce the risk of screw pullout.
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Osseointegration implant (OI) surgery is the latest rehabilitation technology for amputees, where a bone-anchored implant obviates the limitations of traditional socket prostheses. The bone mineral density (BMD) in the periprosthetic and other anatomical regions can be used to assess bone remodelling following OI surgery. Currently, limited studies have used BMD measurements in reporting post-operative OI outcomes and the association between the maintenance of BMD and implant efficacy has remained elusive. This review captured and analysed all studies that have reported the BMD as an objective outcome measure in patients with trans-femoral or trans-tibial OI. The PubMed, Medline, Scopus and Web of Science databases were searched using the terms 'amputation', 'osseointegration' and 'bone mineral density'. A total of 6 studies involving human participants were included for analysis. All studies used dual X-ray absorptiometry and/or X-rays for measuring BMD. Rehabilitation of trans-femoral or trans-tibial amputation using OI may help restore healthy BMD by enabling physiological bone loading. However, there is a low correlation between the BMD around the OI and the success of OI surgery or the risk of periprosthetic fractures. This review summarises the current evidence on BMD assessment in OI for lower limb amputee rehabilitation. Despite the great variability in the results, the available evidence suggests that OI may help restore BMD following surgery. The limited evidence calls for further investigation, as well as the development of a standard BMD measurement protocol.
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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.
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Three-dimensional (3D) bioprinting has advantages for constructing artificial skin tissues in replicating the structures and functions of native skin. Although many studies have presented improved effect of printing skin substitutes in wound healing, using hydrogel inks to fabricate 3D bioprinting architectures with complicated structures, mimicking mechanical properties, and appropriate cellular environments is still challenging. Inspired by collagen nanofibers withstanding stress and regulating cell behavior, a patterned nanofibrous film was introduced to the printed hydrogel scaffold to fabricate a composite artificial skin substitute (CASS). The artificial dermis was printed using gelatin-hyaluronan hybrid hydrogels containing human dermal fibroblasts with gradient porosity and integrated with patterned nanofibrous films simultaneously, while the artificial epidermis was formed by seeding human keratinocytes upon the dermis. The collagen-mimicking nanofibrous film effectively improved the tensile strength and fracture resistance of the CASS, making it sewable for firm implantation into skin defects. Meanwhile, the patterned nanofibrous film also provided the biological cues to guide cell behavior. Consequently, CASS could effectively accelerate the regeneration of large-area skin defects in mouse and pig models by promoting re-epithelialization and collagen deposition. This research developed an effective strategy to prepare composite bioprinting architectures for enhancing mechanical property and regulating cell behavior, and CASS could be a promising skin substitute for treating large-area skin defects.
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Bioimpressão , Nanofibras , Impressão Tridimensional , Pele Artificial , Humanos , Nanofibras/química , Animais , Camundongos , Suínos , Hidrogéis/química , Fibroblastos/citologia , Engenharia Tecidual , Queratinócitos/citologia , Alicerces Teciduais/química , Ácido Hialurônico/química , Gelatina/químicaRESUMO
Excessive bone marrow adipocytes (BMAds) accumulation often occurs under diverse pathophysiological conditions associated with bone deterioration. Estrogen-related receptor α (ESRRA) is a key regulator responding to metabolic stress. Here, we show that adipocyte-specific ESRRA deficiency preserves osteogenesis and vascular formation in adipocyte-rich bone marrow upon estrogen deficiency or obesity. Mechanistically, adipocyte ESRRA interferes with E2/ESR1 signaling resulting in transcriptional repression of secreted phosphoprotein 1 (Spp1); yet positively modulates leptin expression by binding to its promoter. ESRRA abrogation results in enhanced SPP1 and decreased leptin secretion from both visceral adipocytes and BMAds, concertedly dictating bone marrow stromal stem cell fate commitment and restoring type H vessel formation, constituting a feed-forward loop for bone formation. Pharmacological inhibition of ESRRA protects obese mice against bone loss and high marrow adiposity. Thus, our findings highlight a therapeutic approach via targeting adipocyte ESRRA to preserve bone formation especially in detrimental adipocyte-rich bone milieu.
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Adipócitos , Medula Óssea , Leptina , Osteogênese , Receptores de Estrogênio , Animais , Osteogênese/genética , Adipócitos/metabolismo , Adipócitos/citologia , Camundongos , Leptina/metabolismo , Leptina/genética , Medula Óssea/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/genética , Células-Tronco Mesenquimais/metabolismo , Obesidade/metabolismo , Obesidade/patologia , Obesidade/genética , Receptor ERRalfa Relacionado ao Estrogênio , Receptor alfa de Estrogênio/metabolismo , Receptor alfa de Estrogênio/genética , Feminino , Masculino , Camundongos Endogâmicos C57BL , Transdução de Sinais , Células da Medula Óssea/metabolismo , Camundongos KnockoutRESUMO
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.
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Vértebras Cervicais , Análise de Elementos Finitos , Cifose , Tração , Humanos , Tração/métodos , Vértebras Cervicais/diagnóstico por imagem , Cifose/fisiopatologia , Cifose/diagnóstico por imagem , Cifose/cirurgia , Estresse Mecânico , Tomografia Computadorizada por Raios X , Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/fisiopatologia , Masculino , Cuidados Pré-Operatórios/métodos , Fenômenos BiomecânicosRESUMO
The sleep-wake cycle regulates interstitial fluid and cerebrospinal fluid (CSF) tau levels in both mouse and human by mechanisms that remain unestablished. Here, we reveal a novel pathway by which wakefulness increases extracellular tau levels in mouse and humans. In mice, higher body temperature (BT) associated with wakefulness and sleep deprivation increased CSF tau. In vitro, wakefulness temperatures upregulated tau secretion via a temperature-dependent increase in activity and expression of unconventional protein secretion pathway-1 components, namely caspase-3-mediated C-terminal cleavage of tau (TauC3), and membrane expression of PIP2 and syndecan-3. In humans, the increase in both CSF and plasma tau levels observed post-wakefulness correlated with BT increase during wakefulness. Our findings suggest sleep-wake variation in BT may contribute to regulating extracellular tau levels, highlighting the importance of thermoregulation in pathways linking sleep disturbance to neurodegeneration, and the potential for thermal intervention to prevent or delay tau-mediated neurodegeneration.
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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.
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IMPORTANCE: Most patients use a traditional socket prosthesis (TSP) to ambulate independently following transtibial amputation. However, these patients generally require prosthesis repairs more than twice annually and an entirely new prosthesis every two years. Furthermore, transtibial amputation patients have four times the skin ulceration rate of transfemoral patients, prompting more frequent prosthesis refitting and diminished use. Trans-Tibial osseointegration (TTOI) is a promising technique to address the limitations of TSP, but remains understudied with only four cohorts totaling 41 total procedures reported previously. Continued concerns regarding the risk of infection and questions as to functional capacity postoperatively have slowed adoption of TTOI worldwide. OBJECTIVE: This study reports the changes in mobility, quality of life (QOL), and the safety profile of the largest described cohort of patients with unilateral TTOI following traumatic amputation. DESIGN: Retrospective observational cohort study. The cohort consisted of patients with data outcomes collected before and after osseointegration intervention. SETTING: A large, tertiary referral, major metropolitan center. PARTICIPANTS: Twenty-one skeletally mature adults who had failed socket prosthesis rehabilitation, with at least two years of post-osseointegration follow-up. MAIN OUTCOMES AND MEASURES: Mobility was evaluated by K-level, Timed Up and Go (TUG), and Six Minute Walk Test (6MWT). QOL was assessed by survey: daily prosthesis wear hours, prosthesis problem experience, general contentment with prosthesis, and Short Form 36 (SF36). Adverse events included any relevant unplanned surgery such as for infection, fracture, implant loosening, or implant failure. RESULTS: All patients demonstrated statistically significant improvement post osseointegration surgery with respect to K-level, TUG, 6MWT, prosthesis wear hours, prosthesis problem experience, general prosthesis contentment score, and SF36 Physical Component Score (p < 0.01 for all). Three patients had four unplanned surgeries: two soft tissue refashionings, and one soft tissue debridement followed eventually by implant removal. No deaths, postoperative systemic complications, more proximal amputations, or periprosthetic fractures occurred. CONCLUSIONS AND RELEVANCE: TTOI is likely to confer mobility and QOL improvements to patients dissatisfied with TSP rehabilitation following unilateral traumatic transtibial amputation. Adverse events are relatively infrequent and not further disabling. Judicious use of TTOI seems reasonable for properly selected patients. LEVEL OF EVIDENCE: 2 (Therapeutic investigation, Observational study with dramatic effect).
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Amputação Traumática , Membros Artificiais , Osseointegração , Qualidade de Vida , Tíbia , Humanos , Masculino , Feminino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Amputação Traumática/cirurgia , Amputação Traumática/reabilitação , Seguimentos , Tíbia/cirurgia , Resultado do Tratamento , Desenho de Prótese , Implantação de PróteseRESUMO
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.
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BACKGROUND: Thyroid carcinoma is the most common endocrinological malignancy, but its spread to bone is rare. Particularly, bone metastases leading to complete resorption of the humerus are extremely uncommon. We aimed to explore factors affecting treatment decision in humeral metastasis by presenting a case and analyze the possible treatments via conducting a literature review. CASE PRESENTATION: We described a case of a 68-year-old woman experiencing chronic pain in her right upper arm for six years. Clinical, radiological, and pathological evaluations confirmed humeral metastasis from thyroid carcinoma. Surgical treatments like tumor removal or limb amputation were suggested for prolonging life and pain relief, but the patient refused them and pursued conservative managements such as herbal medicine, radioactive iodine (131I) therapy, and Levothyroxine Sodium(L-T4). The humeral destruction aggravated gradually, ultimately leading to complete resorption of her right humerus. The patient could not move her right shoulder, but her forearm motion was almost normal; thus, she could complete most of her daily living activities independently. Surgical treatments such as limb amputation were advised but she still refused them for preservation of the residual limb function and preferred conservative managements. CONCLUSION: A personalized multidisciplinary approach is important for patients with bone metastasis. The balance between limb amputation for life-prolonging and pain relief and limb salvage for preservation of residual function and social and psychological well-being should be considered. Our literature review revealed that some novel surgical treatments and techniques are available for bone metastases. This case adds to our current understanding of bone metastases and will contribute to future research and treatments.
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Neoplasias Ósseas , Úmero , Neoplasias da Glândula Tireoide , Idoso , Feminino , Humanos , Neoplasias Ósseas/cirurgia , Úmero/diagnóstico por imagem , Úmero/cirurgia , Radioisótopos do Iodo , Dor , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
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.
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Osteoartrite , Transdução de Sinais , beta Catenina , Humanos , Osteoartrite/metabolismo , Osteoartrite/patologia , Animais , beta Catenina/metabolismo , Via de Sinalização Wnt , NF-kappa B/metabolismo , Proteínas Hedgehog/metabolismo , Proteínas Morfogenéticas Ósseas/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
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.
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Diabetes Mellitus Tipo 2 , Osteoartrite , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Osteoartrite/epidemiologia , Obesidade/complicações , Fatores de Risco , Metabolismo dos LipídeosRESUMO
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.
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Aims: Safety concerns surrounding osseointegration are a significant barrier to replacing socket prosthesis as the standard of care following limb amputation. While implanted osseointegrated prostheses traditionally occur in two stages, a one-stage approach has emerged. Currently, there is no existing comparison of the outcomes of these different approaches. To address safety concerns, this study sought to determine whether a one-stage osseointegration procedure is associated with fewer adverse events than the two-staged approach. Methods: A comprehensive electronic search and quantitative data analysis from eligible studies were performed. Inclusion criteria were adults with a limb amputation managed with a one- or two-stage osseointegration procedure with follow-up reporting of complications. Results: A total of 19 studies were included: four one-stage, 14 two-stage, and one article with both one- and two-stage groups. Superficial infection was the most common complication (one-stage: 38% vs two-stage: 52%). There was a notable difference in the incidence of osteomyelitis (one-stage: nil vs two-stage: 10%) and implant failure (one-stage: 1% vs two-stage: 9%). Fracture incidence was equivocal (one-stage: 13% vs two-stage: 12%), and comparison of soft-tissue, stoma, and mechanical related complications was not possible. Conclusion: This review suggests that the one-stage approach is favourable compared to the two-stage, because the incidence of complications was slightly lower in the one-stage cohort, with a pertinent difference in the incidence of osteomyelitis and implant failure.
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Parathyroid hormone (PTH) is one of the most important hormones for bone turnover and calcium homeostasis. It is unclear how the central nervous system regulates PTH. The subfornical organ (SFO) lies above the third ventricle and modulates body fluid homeostasis. Through retrograde tracing, electrophysiology, and in vivo calcium imaging, we identified the SFO as an important brain nucleus that responds to serum PTH changes in mice. Chemogenetic stimulation of GABAergic neurons in SFO induces decreased serum PTH followed by a decrease in trabecular bone mass. Conversely, stimulation of glutamatergic neurons in the SFO promoted serum PTH and bone mass. Moreover, we found that the blockage of different PTH receptors in the SFO affects peripheral PTH levels and the PTH's response to calcium stimulation. Furthermore, we identified a GABAergic projection from the SFO to the paraventricular nucleus, which modulates PTH and bone mass. These findings advance our understanding of the central neural regulation of PTH at cellular and circuit level.
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Líquidos Corporais , Órgão Subfornical , Animais , Camundongos , Hormônio Paratireóideo/farmacologia , Cálcio , Neurônios GABAérgicosRESUMO
Refractive disorder is the most prevalent cause of visual impairment worldwide. While treatment of refractive errors can bring improvement to quality of life and socio-economic benefits, there is a need for individualization, precision, convenience, and safety with the chosen method. Herein, we propose using pre-designed refractive lenticules based on poly-NAGA-GelMA (PNG) bio-inks photo-initiated by digital light processing (DLP)-bioprinting for correcting refractive errors. DLP-bioprinting allows PNG lenticules to have individualized physical dimensions with precision achievable to 10µm (µm). Material characteristics of PNG lenticules in tests included optical and biomechanical stability, biomimetical swelling and hydrophilic capability, nutritional and visual functionality, supporting its suitability as stromal implants. Cytocompatibility distinguished by morphology and function of corneal epithelial, stromal, and endothelial cells on PNG lenticules suggested firm adhesion, over 90% viability, phenotypic maintenance instead of excessive keratocyte-myofibroblast transformation.In-vitroimmune response analyzed by illumina RNA sequencing in human peripheral blood mononuclear cells indicated that PNG lenticules activated type-2 immunity, facilitating tissue regeneration and suppressing inflammation.In-vivoperformance assessed using intrastromal keratoplasty models in New Zealand white rabbits illustrated that implantation of PNG lenticules maintained stable optical pathway, induced controlled stromal bio-integration and regeneration, avoided complications such as stromal melt, interface scarring, etc, but exerted no adverse effects on the host. Postoperative follow-up examination on intraocular pressure, corneal sensitivity, and tear production remained unaffected by surgery up to 1-month post-implantation of PNG lenticules. DLP-bioprinted PNG lenticule is a bio-safe and functionally effective stromal implants with customizable physical dimensions, providing potential therapeutic strategies in correction of refractive errors.
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Cirurgia da Córnea a Laser , Erros de Refração , Humanos , Animais , Coelhos , Hidrogéis , Células Endoteliais , Leucócitos Mononucleares , Qualidade de Vida , Cirurgia da Córnea a Laser/métodosRESUMO
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.
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Bone void is a novel intuitive morphological indicator to assess bone quality but its use in vertebrae has not been described. This cross-sectional and multi-center study aimed to investigate the distribution of bone voids in the thoracolumbar spine in Chinese adults based on quantitative computed tomography (QCT). A bone void was defined as a trabecular net region with extremely low bone mineral density (BMD) (<40 mg/cm3), detected by an algorithm based on phantom-less technology. A total of 464 vertebrae from 152 patients (51.8 ± 13.4 years old) were included. The vertebral trabecular bone was divided into eight sections based on the middle sagittal, coronal, and horizontal planes. Bone void of the whole vertebra and each section were compared between healthy, osteopenia, and osteoporosis groups and between spine levels. Receiver operator characteristic (ROC) curves were plotted and optimum cutoff points of void volume between the groups were obtained. The total void volumes of the whole vertebra were 124.3 ± 221.5 mm3, 1256.7 ± 928.7 mm3, and 5624.6 ± 3217.7 mm3 in healthy, osteopenia, and osteoporosis groups, respectively. The detection rate of vertebrae with bone voids was higher and the normalized void volume was larger in the lumbar than in thoracic vertebrae. L3 presented the largest void (2165.0 ± 3396.0 mm3), while T12 had the smallest void (448.9 ± 699.4 mm3). The bone void was mainly located in the superior-posterior-right section (40.8 %). Additionally, bone void correlated positively with age and increased rapidly after 55 years. The most significant void volume increase was found in the inferior-anterior-right section whereas the least increase was found in the inferior-posterior-left section with aging. The cutoff points were 345.1 mm3 between healthy and osteopenia groups (sensitivity = 0.923, specificity = 0.932) and 1693.4 mm3 between osteopenia and osteoporosis groups (sensitivity = 1.000, specificity = 0.897). In conclusion, this study demonstrated the bone void distribution in vertebrae using clinical QCT data. The findings provide a new perspective for the description of bone quality and showed that bone void could guide clinical practice such as osteoporosis screening.