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BACKGROUND: Although intervertebral disc degeneration (IVDD) is a critical factor in many spine-related diseases and has an extremely high prevalence in the aging population, the potential pathogenesis remains to be clarified entirely. Immune cells have been found to perform an essential function during the onset and progression of IVDD in recent years. Therefore, we explored the association between immune cell characteristics and IVDD through Mendelian randomization (MR) analysis and further delved into the mediating role of potential metabolites. METHODS: Based on the MR analysis, the association of 731 immune cell phenotypes and 1400 metabolites on IVDD were assessed. Single nucleotide polymorphisms were closely associated the expression levels of immune cell characteristics and the concentrations of metabolites and have been used as instrumental variables for deducing them as risk factors or protective factors for IVDD. In addition, mediation analyses have been performed to identify potential metabolite mediators between immune cell characteristics and IVDD. RESULTS: MR analysis identified 27 immune cell phenotypes and 79 metabolites significantly associated with IVDD. In addition, mediation analysis was performed by selecting the immune cell phenotype that most significantly increased the risk of IVDD - CD86 on monocytes. A total of 4 metabolite-mediated mediation relationships were revealed (3 b-hydroxy-5-cholenoic acid, X-22509, N-acetyl-L-glutamine, and N2-acetyl, N6, N6-dimethyllysine). CONCLUSIONS: The findings of this analysis identified underlying association between immune cell phenotypes, metabolite, and IVDD that may serve as predictive and prognostic clinical biomarkers and benefit IVDD pathogenesis research.
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BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors represent an effective strategy for reducing cardiovascular disease risk. Yet, PCSK9's impact on osteoporosis remains unclear. Hence, we employed Mendelian randomization (MR) analysis for examining PCSK9 inhibitor effects on osteoporosis. METHODS: Single nucleotide polymorphisms (SNPs) for 3-hydroxy-3-methylglutaryl cofactor A reductase (HMGCR) and PCSK9 were gathered from available online databases for European pedigrees. Four osteoporosis-related genome-wide association studies (GWAS) data served as the main outcomes, and coronary artery disease (CAD) as a positive control for drug-targeted MR analyses. The results of MR analyses examined by sensitivity analyses were incorporated into a meta-analysis for examining causality between PCSK9 and HMGCR inhibitors and osteoporosis. RESULTS: The meta-analysis involving a total of 1,263,102 subjects, showed that PCSK9 inhibitors can increase osteoporosis risk (P < 0.05, I2, 39%). However, HMGCR inhibitors are not associated with osteoporosis risk. Additionally, a replication of the analysis was conducted with another exposure-related GWAS dataset, which led to similar conclusions. CONCLUSION: PCSK9 inhibitors increase osteoporosis risk. However, HMGCR inhibitors are unremarkably linked to osteoporosis.
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Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Osteoporose , Inibidores de PCSK9 , Polimorfismo de Nucleotídeo Único , Humanos , Osteoporose/genética , Osteoporose/induzido quimicamente , Osteoporose/epidemiologia , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/metabolismo , Hidroximetilglutaril-CoA Redutases/genéticaRESUMO
BACKGROUND: Osteoporosis and frailty are two common features in the elderly population. Despite many review articles mentioning the association between osteoporosis and frailty, there is a lack of original research directly investigating their relationship. Therefore, this study was conducted to examine the correlation between osteoporosis and frailty. METHODS: We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES), using logistic regression analysis to assess the association of osteoporosis with the frailty index. In addition, we further explored the causal relationship between them using Mendelian randomization (MR) study. RESULTS: In the cross-sectional study, 19,091 non-frailty participants and 5878 frailty participants were included in this study. We observed a significant positive association between osteoporosis and frailty after adjusting for demographic characteristics, body mass index (BMI), smoking, and alcohol use (OR = 1.454, 95% CI [1.142,1.851], P = 0.003). Moreover, the MR study showed a bidirectional causal relationship between osteoporosis and frailty. When osteoporosis was used as an exposure factor, the frailty pooled OR value calculated utilizing the inverse variance weighted (IVW) method was 2.81 (95% CI [1.69, 4.68], P = 6.82 × 10- 5). When frailty was used as an exposure factor, the OR value calculated using the IVW method was 1.01 (95% CI [1.00,1.01], P = 3.65 × 10- 7). CONCLUSIONS: Osteoporosis was positively correlated with frailty, and the results remained robust after adjusting for covariates. Further, MR studies have shown a bidirectional causal relationship between osteoporosis and frailty.
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Fragilidade , Análise da Randomização Mendeliana , Osteoporose , Humanos , Estudos Transversais , Osteoporose/epidemiologia , Osteoporose/genética , Osteoporose/complicações , Feminino , Masculino , Fragilidade/genética , Fragilidade/epidemiologia , Idoso , Inquéritos Nutricionais , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Idoso FragilizadoRESUMO
The cure rate for patients with osteosarcoma (OS) has stagnated over the past few decades. Penfluridol, a first-generation antipsychotic, has demonstrated to prevent lung and esophageal malignancies from proliferation and metastasis. However, the effect of penfluridol on OS and its underlying molecular mechanism remains unclear. This study revealed that penfluridol effectively inhibited cell proliferation and migration, and induced G2/M phase arrest in OS cells. In addition, penfluridol treatment was found to increased reactive oxygen species (ROS) levels in OS cells. Combined with the RNA-Seq results, the anti-OS effect of penfluridol was hypothesized to be attributed to the induction of ferroptosis. Western blot results showed that penfluridol promoted intracellular Fe2+ concentration, membrane lipid peroxidation, and decreased intracellular GSH level to induce ferroptosis. Further studies showed that p62/Keap1/Nrf2 signaling pathway was implicated in penfluridol-induced ferroptosis in OS cells. Overexpression of p62 effectively reversed penfluridol-induced ferroptosis. In vivo, penfluridol effectively inhibited proliferation and prolonged survival in xenograft tumor model. Therefore, penfluridol is a promising drug targeting OS in the future.
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Proliferação de Células , Ferroptose , Proteína 1 Associada a ECH Semelhante a Kelch , Camundongos Nus , Fator 2 Relacionado a NF-E2 , Osteossarcoma , Penfluridol , Transdução de Sinais , Ferroptose/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Humanos , Transdução de Sinais/efeitos dos fármacos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Osteossarcoma/metabolismo , Animais , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Linhagem Celular Tumoral , Penfluridol/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Neoplasias Ósseas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Movimento Celular/efeitos dos fármacosRESUMO
ABSTRACT: Glycoprotein VI (GPVI) plays a key role in collagen-induced platelet aggregation. Affimers are engineered binding protein alternatives to antibodies. We screened and characterized GPVI-binding Affimers as novel tools to probe GPVI function. Among the positive clones, M17, D22, and D18 bound GPVI with the highest affinities (dissociation constant (KD) in the nanomolar range). These Affimers inhibited GPVI-collagen-related peptide (CRP)-XL/collagen interactions, CRP-XL/collagen-induced platelet aggregation, and D22 also inhibited in vitro thrombus formation on a collagen surface under flow. D18 bound GPVI dimer but not monomer. GPVI binding was increased for D18 but not M17/D22 upon platelet activation by CRP-XL and adenosine 5'-diphosphate. D22 but not M17/D18 displaced nanobody 2 (Nb2) binding to GPVI, indicating similar epitopes for D22 with Nb2 but not for M17/D18. Mapping of binding sites revealed that D22 binds a site that overlaps with Nb2 on the D1 domain, whereas M17 targets a site on the D2 domain, overlapping in part with the glenzocimab binding site, a humanized GPVI antibody fragment antigen-binding fragment. D18 targets a new region on the D2 domain. We found that D18 is a stable noncovalent dimer and forms a stable complex with dimeric GPVI with 1:1 stoichiometry. Taken together, our data demonstrate that Affimers modulate GPVI-ligand interactions and bind different sites on GPVI D1/D2 domains. D18 is dimer-specific and could be used as a tool to detect GPVI dimerization or clustering in platelets. A dimeric epitope regulating ligand binding was identified on the GPVI D2 domain, which could be used for the development of novel bivalent antithrombotic agents selectively targeting GPVI dimer on platelets.
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Plaquetas , Agregação Plaquetária , Glicoproteínas da Membrana de Plaquetas , Ligação Proteica , Multimerização Proteica , Glicoproteínas da Membrana de Plaquetas/metabolismo , Glicoproteínas da Membrana de Plaquetas/química , Humanos , Plaquetas/metabolismo , Ligantes , Agregação Plaquetária/efeitos dos fármacos , Sítios de Ligação , Colágeno/metabolismo , Colágeno/química , Proteínas de Transporte , PeptídeosRESUMO
Objective: Interleukin-6 (IL-6) is a multiple-effect cell factor implicated in the etiopathogenesis of several rheumatologic disorders. The blockade of the IL-6 pathway via IL6R inhibitors effectively treats these disorders. However, the clinical significance of the IL6R blockade for ankylosing spondylitis (AS) therapy remains controversial. With advances in genomics, increasing evidence has revealed the role of heritability in the etiology of disease, and Mendelian randomization (MR) analyses are being used more broadly to infer causation. Therefore, this MR study aims to evaluate the potential therapeutic utility of IL6R-targeted approaches in AS. Methods: The C-reactive protein (CRP) level was used as an exposure factor, and rheumatoid arthritis (RA) was used as a positive control. As-related genome-wide association study (GWAS) data were used as the primary outcome of drug-targeted MR analyses to test the relation between IL6R blockers and AS. Inverse variance weighting (IVW) is the primary analytical approach. Various sensitivity tests were performed to check the robustness and trustworthiness of the causality estimation, including consistency, heterogeneity, and pleiotropy analyses. In addition, repeated analysis was conducted using different GWAS data related to exposures and outcomes to examine the results for stability. Results: According to the IVW results, IL6R inhibitors significantly reduced the risk of AS in ukb-b-18194 (OR: 0.995, 95% CI 0.993-0.996, P = 5.12 × 10-08) and ukb-a-88 (OR: 0.994, 95% CI 0.993-0.996, P = 6.25 × 10-15). Moreover, repeated analyses were performed using different exposure-related GWAS data, yielding similar results, ukb-b-18194 (OR: 0.995, 95% CI 0.993-0.997, P = 1.25 × 10-06) and ukb-a-88 (OR: 0.995, 95% CI 0.994-0.997, P = 7.81 × 10-09). Heterogeneity analyses and pleiotropy analyses indicated no significant heterogeneity or pleiotropy. Conclusion: This MR analysis result further validates that the IL-6 pathway may contribute to the pathogenesis of AS and that the inhibition of IL6R reduces the risk of AS. These findings may guide future studies and provide more favorable drug treatment options for people at high risk of AS.
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A new loach species, Oreonectesandongensissp. nov. is described from the Guangxi Zhuang Autonomous Region, China. The new species can be differentiated from other members of the genus by combinations of characters: a developed posterior chamber of the swim bladder, 13-14 branched caudal-fin rays, 8-16 lateral-line pores, body width 12-15% of standard length (SL), interorbital width 42-47% of head length (HL), and caudal peduncle length 11-16% of SL. Bayesian inference phylogenetic analysis based on mitochondrial Cyt b provided strong support for validity of O.andongensissp. nov. (uncorrected p-distance 6.0-7.5%).
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Phosphatidylinositol 3-kinase (PI3K) is frequently hyperactivated in cancer, playing pivotal roles in the pathophysiology of both malignant and immune cells. The impact of PI3K inhibitors on the tumor microenvironment (TME) within lung cancer remains largely unknown. In this study, we explored the regulatory effects of GNE-493, an innovative dual inhibitor of PI3K and mammalian target of rapamycin (mTOR), on the TME of lung cancer. First, through the analysis of The Cancer Genome Atlas-lung squamous cell carcinoma (LUSC) cohort, we found PIK3CA to be related to CD8 T cells, which may affect the overall survival rate of patients by affecting CD8 function. We herein demonstrated that GNE-493 can significantly inhibit tumor cell proliferation and promote cell apoptosis while increasing the expression of the immunogenic death-related molecules CRT and HSP70 using in vitro cell proliferation and apoptosis experiments on the murine KP lung cancer cell line and human A549 lung cancer cell line. Next, through the establishment of an orthotopic tumor model in vivo, it was found that after GNE-493 intervention, the infiltration of CD4+ and CD8+ T cells in mouse lung tumor was significantly increased, and the expression of CRT in tumors could be induced to increase. To explore the mechanisms underlying PI3K inhibition-induced changes in the TME, the gene expression differences of T cells in the control group versus GNE-493-treated KP tumors were analyzed by RNA-seq, and the main effector pathway of anti-tumor immunity was identified. The IFN/TNF family molecules were significantly upregulated after GNE-493 treatment. In summary, our findings indicate that GNE-493 promotes immunogenic cell death in lung cancer cells, and elucidates its regulatory impact on molecules associated with the adaptive immune response. Our study provides novel insights into how PI3K/mTOR inhibitors exert their activity by modulating the tumor-immune interaction.
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Morte Celular Imunogênica , Neoplasias Pulmonares , Fosfatidilinositol 3-Quinase , Inibidores de Fosfoinositídeo-3 Quinase , Animais , Humanos , Camundongos , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Classe I de Fosfatidilinositol 3-Quinases , Morte Celular Imunogênica/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Fosfatidilinositol 3-Quinase/metabolismo , Transdução de Sinais , Microambiente Tumoral , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Células A549 , Feminino , Camundongos Endogâmicos C57BLRESUMO
Bone metastases caused by breast cancer pose a major challenge to the successful treatment of breast cancer patients. Many researchers have suggested that herbal medicines are extremely effective at preventing and treating cancer-associated osteolysis. Previous studies have revealed that Morusin (MOR) is cytotoxic to many cancer cells ex vivo. Nevertheless, how MOR contributes to osteolysis induced by breast cancer is still unknown, and the potential mechanism of action against osteolysis is worthy of further study. The protective effect and molecular mechanism of MOR in inhibiting breast cancer cell-induced osteolysis were verified by experiments and network pharmacology. Cell function was assessed by cell proliferation, osteoclast (OC) formation, bone resorption, and phalloidin staining. Tumour growth was examined by micro-CT scanning in vivo. To identify potential MOR treatments, the active ingredient-target pathway of breast cancer was screened using network pharmacology and molecular docking approaches. This study is the first to report that MOR can prevent osteolysis induced by breast cancer cells. Specifically, our results revealed that MOR inhibits RANKL-induced osteoclastogenesis and restrains the proliferation, invasion and migration of MDA-MB-231 breast cells through restraining the PI3K/AKT/MTOR signalling pathway. Notably, MOR prevented bone loss caused by breast cancer cell-induced osteolysis in vivo, indicating that MOR inhibited the development of OCs and the resorption of bone, which are essential for cancer cell-associated bone distraction. This study showed that MOR treatment inhibited osteolysis induced by breast cancer in vivo. MOR inhibited OC differentiation and bone resorption ex vivo and in vivo and might be a potential drug candidate for treating breast cancer-induced osteolysis.
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Neoplasias da Mama , Osteólise , Fosfatidilinositol 3-Quinase , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Feminino , Humanos , Camundongos , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Nus , Simulação de Acoplamento Molecular , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteólise/metabolismo , Osteólise/tratamento farmacológico , Osteólise/patologia , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ligante RANK/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismoRESUMO
Eugenol (EU) has been shown to ameliorate experimental colitis due to its anti-oxidant and anti-inflammatory bioactivities. In this study, DSS-induced acute colitis was established and applied to clarify the regulation efficacy of EU on intestinal barrier impairment and macrophage polarization imbalance along with the inflammatory response. Besides, the adjusting effect of EU on macrophages was further investigated in vitro. The results confirmed that EU intervention alleviated DSS-induced colitis through methods such as restraining weight loss and colonic shortening and decreasing DAI scores. Microscopic observation manifested that EU maintained the intestinal barrier integrity in line with the mucus barrier and tight junction protection. Furthermore, EU intervention significantly suppressed the activation of TLR4/MyD88/NF-[Formula: see text]B signaling pathways and pro-inflammatory cytokines gene expressions, while enhancing the expressions of anti-inflammatory cytokines. Simultaneously, WB and FCM analyses of the CD86 and CD206 showed that EU could regulate the DSS-induced macrophage polarization imbalance. Overall, our data further elucidated the mechanism of EU's defensive effect on experimental colitis, which is relevant to the protective efficacy of intestinal barriers, inhibition of oxidative stress and excessive inflammatory response, and reprogramming of macrophage polarization. Hence, this study may facilitate a better understanding of the protective action of the EU against UC.
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Colite , Eugenol , Animais , Camundongos , Eugenol/farmacologia , Eugenol/uso terapêutico , Fator 88 de Diferenciação Mieloide/genética , Receptor 4 Toll-Like/genética , Colite/induzido quimicamente , Colite/tratamento farmacológico , Proteínas Adaptadoras de Transdução de Sinal , Colo , Citocinas , Macrófagos , Anti-Inflamatórios , Sulfato de Dextrana , NF-kappa B , Camundongos Endogâmicos C57BL , Modelos Animais de DoençasRESUMO
OBJECTIVE: This meta-analysis aims to refine the understanding of the optimal choice between different cage shapes in transforaminal lumbar interbody fusion (TLIF) by systematically comparing perioperative data, radiological outcomes, clinical results, and complications associated with banana-shaped and straight bullet cages. METHODS: A meticulous literature search encompassing PubMed, Embase, Scopus, Web of Science, China Knowledge Network, and Wanfang Data was executed up to October 5, 2023. Inclusion criteria focused on studies comparing banana-shaped and straight bullet cages in TLIF. The quality of included studies was assessed using appropriate tools such as the Newcastle-Ottawa Scale (NOS) for nonrandomized studies. Rigorous evaluations were performed for radiographic outcomes, including disc height (DH), segmental lordosis (SL), lumbar lordosis (LL), subsidence, and fusion rates. Clinical outcomes were meticulously evaluated using visual analogue scale (VAS), Oswestry Disability Index (ODI), and complications. RESULTS: The analysis incorporated 7 studies, involving 573 patients (297 with banana-shaped cages, 276 with straight cages), all with NOS ratings exceeding 5 stars. No statistically significant differences were observed in operative time, blood loss, or hospitalization between the 2 cage shapes. Banana-shaped cages exhibited greater changes in DH (p = 0.001), SL (p = 0.02), and LL (p = 0.01). Despite statistically higher changes in ODI for straight cages (26.33, p < 0.0001), the actual value remained similar to banana-shaped cages (26.15). Both cage types demonstrated similar efficacy in VAS, complication rates, subsidence, and fusion rates. CONCLUSION: Although banana-shaped cages can excel in restoring DH, SL, and LL, straight bullet cages can provide comparable functional improvements, pain relief, and complication rates.
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Osteosarcoma is a prevalent kind of primary bone malignancy. Trifluoperazine, as an antipsychotic drug, has anti-tumor activity against a variety of cancers. Nevertheless, the impact of trifluoperazine on osteosarcoma is unclear. Our investigation aimed to explore the mechanism of trifluoperazine's effect on osteosarcoma. We found that trifluoperazine inhibited 143B and U2-OS osteosarcoma cell proliferation in a method based on the dose. Furthermore, it was shown that trifluoperazine induced the accumulation of reactive oxygen species (ROS) to cause mitochondrial damage and induced mitophagy in osteosarcoma cells. Finally, combined with RNA-seq results, we first demonstrated the AMPK/mTOR/ULK1 signaling pathway as a potential mechanism of trifluoperazine-mediated mitophagy in osteosarcoma cells and can be suppressed by AMPK inhibitor Compound C.
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Mitofagia , Osteossarcoma , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Trifluoperazina/farmacologia , Autofagia , Apoptose , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Osteossarcoma/metabolismo , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismoRESUMO
Inflammatory myofibroblastic tumors (IMTs) of the heart are rarely observed in the eldly. We report a case involving an elderly woman with an IMT situated on the right atrial wall. The tumor was fully excised. The patient had a smooth recovery post-surgery and remained free of recurrence for three years.
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Fibrilação Atrial , Neoplasias Cardíacas , Feminino , Humanos , Idoso , Fibrilação Atrial/cirurgia , Coração , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/cirurgiaRESUMO
The spike protein of SARS-CoV-2 as well as its receptor binding domain (RBD) has been demonstrated to be capable of activating the release of pro-inflammatory mediators in endothelial cells and immune cells such as monocytes. However, the effects of spike protein or its RBD on airway epithelial cells and mechanisms underlying these effects have not been adequately characterized. Here, we show that the RBD of spike protein alone can induce bronchial epithelial inflammation in a manner of ATP/P2Y2 dependence. Incubation of human bronchial epithelia with RBD induced IL-6 and IL-8 release, which could be inhibited by antibody. The incubation of RBD also up-regulated the expression of inflammatory indicators such as ho-1 and mkp-1. Furthermore, ATP secretion was observed after RBD treatment, P2Y2 receptor knock down by siRNA significantly suppressed the IL-6 and IL-8 release evoked by RBD. Additionally, S-RBD elevated the phosphorylation level of ERK1/2, and the effect that PD98059 can inhibit the pro-inflammatory cytokine release suggested the participation of ERK1/2. These novel findings provide new evidence of SARS-CoV-2 on airway inflammation and introduce purinergic signaling as promising treatment target.
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COVID-19 , Glicoproteína da Espícula de Coronavírus , Humanos , Glicoproteína da Espícula de Coronavírus/metabolismo , Sistema de Sinalização das MAP Quinases , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Células Endoteliais/metabolismo , SARS-CoV-2/metabolismo , COVID-19/metabolismo , Transdução de Sinais , Mucosa Respiratória/metabolismo , Inflamação/metabolismo , Trifosfato de Adenosina/farmacologia , Trifosfato de Adenosina/metabolismo , Ligação ProteicaRESUMO
Background: Hip fractures, including femoral neck fractures, are a significant cause of morbidity and mortality in the elderly population and are typically diagnosed using plain radiography. However, diagnosing non-displaced femoral neck fractures can be challenging due to their subtle appearance on hip radiographs. Previous deep-learning models have shown low accuracy in identifying these fractures on anteroposterior (AP) radiographs; however, no studies have used lateral radiographs. This study aimed to evaluate the potential of using deep-learning with both AP and lateral hip radiographs to automatically identify non-displaced femoral neck fractures. Methods: We conducted a retrospective analysis of patients with femoral neck fractures at The First Affiliated Hospital of Xiamen University. All the hip radiographs were reviewed, and cases of non-displaced femoral neck fractures were included in the study. Additionally, 439 participants with normal hip radiographs were also included in the study. A vision transformer (Vit) model was developed using 1,536 AP and lateral hip radiograph. The model's performance was compared to the performance of two groups of human observers: an expert group comprising orthopedic surgeons and radiologists, and a non-expert group, including emergency physicians and general practice doctors. We also carried out the external validation using two additional data sets to assess the generalizability of the model. Results: The Vit model showed exceptional performance in detecting non-displaced femoral neck fractures on paired AP and lateral hip radiographs, achieving a binary accuracy of 95.8% [95% confidence interval (CI): 94.9%, 96.8%] and an area under the curve (AUC) of 0.988. Compared to the human observers, the model had a higher accuracy of 96.7% (95% CI: 93.9%, 99.5%) on the paired AP and lateral hip radiographs, while the accuracy of the expert group was 90.5% (95% CI: 85.7%, 95.2%). Further, the model maintained good performance during the external validation, with an AUC of 0.959 on the paired AP and lateral views. Conclusions: Our Vit model showed expert-level performance in identifying non-displaced femoral neck fractures on paired AP and lateral hip radiographs. This model has the potential to enhance diagnosis accuracy and improve patient outcomes by reducing the need for additional examinations and preoperative time.
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BACKGROUND/AIM: As one of the common clinical diseases, fractures have many causes, mechanisms, healing and influencing factors; especially fracture healing is a long-term and complex process. Animal fracture models can simulate the various states of human fractures, and on this basis, the prevention, mechanism, and treatment of fractures can be studied to further guide clinical practice. MATERIALS AND METHODS: Here, we developed a novel and portable device to create a closed fracture model in mice. We then compared this novel closed fracture model with the traditional open model in multiple dimensions to evaluate the modelling process of establishment and healing. The two models were evaluated by imaging, immunostaining, and behavioral tests, which fully demonstrated the stability, universality and operability of the modified fracture model in mice. RESULTS: Surgical quality assessment revealed that the closed fracture model had a shorter operation time and smaller wound than the open model. X-ray and micro-CT results showed no differences between the two models in the evaluation of radiographic and morphological changes during fracture healing. Histological examination revealed the process of the typical intrachondral osteogenic pathway after fracture. Moreover, animal gait analysis indicated reduced postoperative pain in the closed group compared to the open group. CONCLUSION: This study provides a constructive strategy for a closed fracture model in mice and demonstrates the effectiveness and feasibility of the closed fracture model in studying the typical intrachondral osteogenic pathway of fractures from multiple dimensions.
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Fraturas Ósseas , Fraturas Fechadas , Camundongos , Humanos , Animais , Fraturas Ósseas/diagnóstico por imagem , Consolidação da Fratura , Modelos Animais , Osteogênese , Resultado do TratamentoRESUMO
ABSTRACT Objective: To investigate the accuracy of aortic dimensions measured by Revolution™ computed tomography (CT) in infants with complex coarctation of the aorta (CoA) and to further analyze the utility of the degree of CoA in predicting the risk of prolonged postoperative cardiac intensive care unit stay. Methods: A total of 30 infants with complex CoA who underwent surgical correction from January 2020 to July 2022 were retrospectively enrolled. General demographic data, preoperative imaging, and perioperative outcomes were collected. Univariate and multivariate analyses were performed to investigate predictors of prolonged postoperative cardiac intensive care unit stay, and the reliability of the CT measurements was assessed by the intraclass correlation coefficient. Results: All infants were divided into a mild or severe CoA group. The duration of mechanical ventilation and cardiac intensive care unit stay in the mild CoA group were significantly lower than those in the severe CoA group. After multivariate analysis, we found that the degree of CoA and age at surgery were significant predictors of prolonged postoperative cardiac intensive care unit stay. The intraclass correlation coefficient between CT measurements and intraoperative measurements was between 0.937 and 0.975, and the measurement results had good reliability. Conclusion: CT angiography can provide a comprehensive and accurate preoperative evaluation of aortic dimensions measured in infants with complex CoA. The degree of CoA is an independent risk factor for prolonged postoperative cardiac intensive care unit stay in infants with complex CoA.