Combining robotics and 3D printing facilitates closed reduction of humeral shaft fractures using a minimally invasive plate as a reduction template: A proof-of-concept study.

BACKGROUND: Minimally invasive percutaneous plate osteosynthesis for humeral shaft fractures (HSFs) has limitations due to malreduction and radiation exposure. To address these limitations, we integrated robotics and 3D printing by incorporating plates as reduction templates. METHOD: The innovative technology facilitated closed reduction of HSFs in the operating theatre using 18 models with cortical marking holes. The dataset of the precontoured plate was imported into 3D planning software for virtual fixation and screw path planning. The models were divided into half to simulate transverse fractures. During the operation, the software generated drilling trajectories for robot navigation, and precise plate installation achieved automatic fracture reduction. RESULTS: The evaluation results of reduction accuracy revealed variations in length, apposition, alignment, and rotation that meet the criteria for anatomic reduction. High interoperator reliabilities were observed for all parameters. CONCLUSIONS: The proposed technology achieved anatomic reduction in simulated bones.

Deciphering two decades of cellular reprogramming in cancer: A bibliometric analysis of evolving trends and research frontiers.

Recent research has reevaluated the traditional view of cancer's linear progression and recurrence by introducing cellular reprogramming a process in which cancer cells can their state under certain conditions. This change is driven by a combination of genetic and epigenetic factors, with pivotal roles played by key genes, and pathways, notably Wnt and Notch. The complexity of cancer's behavior is further influenced by factors such as the epithelial-mesenchymal transition (EMT) and therapy-induced stress, both of which are significant contributors to cancer recurrence. In this context bibliometric analysis emerges as a crucial tool for evaluating the impacts and trends within scientific literature. Our study utilized bibliometrics to analysis the role of cellular reprogramming oncology over the past two decades, highlighting its potential to improve cancer treatment outcomes. In conducting this analysis, we searched for literature search on cellular reprogramming (CR) in the Web of Science database, covering the years 2002-2022. We employed visualization tools like Citespace, VOSviewer, and Bibliometrix to analyze the collected data resulting in a dataset of 3102 articles. The United States and China emerged as leading contributors to this field, with the University of Texas MD Anderson Cancer Center being the most prolific institution. Menendez was the most influential scholar in this research domain. Cancers was the journal with the most publications on this subject. The most local-cited document was the article titled "Hallmarks of Cancer: The Next Generation". A comprehensive analysis has been conducted based on keywords and cited references. In recent years, the research emphasis has shifted to "extracellular vesicles," "cancer therapy," and "cellular plasticity". Therefore, this analysis uses bibliometrics to chart cutting-edge progress in cancer's cellular reprogramming, aiding experts to quickly understand and innovate in this crucial area.

Ginkgolide B effectively mitigates neuropathic pain by suppressing the activation of the NLRP3 inflammasome through the induction of mitophagy in rats.

Neuropathic pain is a pathological state induced by the aberrant generation of pain signals within the nervous system. Ginkgolide B(GB), an active component found of Ginkgo. biloba leaves, has neuroprotective properties. This study aimed to explore the effects of GB on neuropathic pain and its underlying mechanisms. In the in vivo study, we adopted the rat chronic constriction injury model, and the results showed that GB(4 mg/kg) treatment effectively reduced pain sensation in rats and decreased the expressions of Iba-1 (a microglia marker), NLRP3 inflammasome, and inflammatory factors, such as interleukin (IL)-1ß, in the spinal cord 7 days post-surgery. In the in vitro study, we induced microglial inflammation using lipopolysaccharide (500 ng/mL) / adenosine triphosphate (5 mM) and treated it with GB (10, 20, and 40 µM). GB upregulated the expression of mitophagy proteins, such as PINK1, Parkin, LC3 II/I, Tom20, and Beclin1, and decreased the cellular production of reactive oxygen species. Moreover, it lowered the expression of inflammation-related proteins, such as Caspase-1, IL-1ß, and NLRP3 in microglia. However, this effect was reversed by Parkin shRNA/siRNA or the autophagy inhibitor 3-methyladenine (5 mM). These findings reveal that GB alleviates neuropathic pain by mitigating neuroinflammation through the activation of PINK1-Parkin-mediated mitophagy.

A novel technology integrating robotics and 3D printing for closed reduction of tibia shaft fracture with MIPPO:A proof-of-concept study.

Less invasive fixation techniques, such as intramedullary nailing (IMN) and minimally invasive percutaneous plate osteosynthesis (MIPPO), are now the preferred choices for treating tibia shaft fractures (TSFs). However, malreduction and radiation exposure are the main deficiencies associated with less invasive fixation techniques, especially when assessing rotation around the shaft axis intra-operatively. The purpose of this study was to investigate the feasibility and reduction accuracy of an innovative technology that integrates robotics and 3D printing for achieving anatomical reduction of TSFs with MIPPO. The surgical workflow from a standardized CT protocol, via 3D reconstruction, 3D printing tibia model, pre-contouring plate, 3D scanning plate, 3D planning of the trajectories of the robot, and use of a commercial surgical robot, robot-assisted screw hole drilling, to automatic fracture reduction through precise installation of the plate was described. The reduction accuracy was evaluated by an optical tracking system. The mean variations of 1.95 ± 1.36mm in length, 1.63 ± 0.92 mm in apposition, 2.78 ± 1.69° in alignment, and 1.99 ± 1.81° in rotation. The interoperator reliabilities were almost perfect, with values of 0.91, 0.93, 0.92, and 0.90, respectively. The proposed technology achieved anatomic reduction on phantom bones.

Enhancing propellant performance through intermolecular interactions: cyclodextrin-based MOF loading in nitrocellulose.

Metal-organic frameworks (MOFs) offer promising opportunities for modifying energetic materials due to their micro-porous structure and high performance. In this study, we present a novel green MOF named cyclodextrin-MOF (CD-MOF), which incorporates potassium ions, synthesized using a simple methanol vapor diffusion approach. The CD-MOF incorporates potassium ions and enhances propellant performance through intermolecular force optimization with nitrocellulose (NC). Molecular dynamics simulations reveal stronger interactions between the CD-MOF and NC. The loading of the CD-MOF within NC forms a stable structure with resistance to migration and defense against crystalline precipitation and water absorption. Notably, in static combustion and pyrolysis tests, the CD-MOF exhibits efficient flame and flash inhibition. The thermal degradation and cauterization of the CD-MOF resulted in the formation of a complex microporous material capable of absorbing flammable and harmful gases such as CO, NO, NO2, and N2O. These findings shed light on the superior performance of the CD-MOF compared to conventional inorganic salts, and the comprehensive characterization and molecular simulations provide insights into the unique properties and applications of the CD-MOF, emphasizing its significant contribution to the field of green propellants.

Medial minimally invasive percutaneous plate osteosynthesis for humeral shaft fractures: a case series and novel technique description.

INTRODUCTION: Minimally Invasive Percutaneous Plate Osteosynthesis (MIPPO) is increasingly favored for treating humeral shaft fractures (HSFs). However, conventional MIPPO techniques pose challenges in fixing fractures near fossa olecranon and carry a risk of iatrogenic radial nerve palsy. A novel technique using a medial MIPPO for treating humeral shaft fractures (HSFs) is described. Results of clinical follow-up are presented. MATERIALS AND METHODS: This study is a retrospective case series study. Twenty-one patients (mean age 43.9 ± 17.66 [22‒81] years) with HSFs were treated with the novel MIPPO fixation method. Clinical outcomes including time for radiographic consolidation, Disabilities of the Arm, Shoulder, and Hand (DASH) score, and complications were assessed at the last follow-up. The mean follow-up was 26 ± 17.12 (range 12-67) months. RESULTS: All patients had a bony union at a mean of 15.76 ± 6.74 (range 8-40) weeks based on X-ray with an early and aggressive range of motion. The complication rate was 0. The mean DASH score was3.29 ± 4.09 (range 0-14.17) at the time of the last follow-up. The mean screw density was 0.49 ± 0.1 (range 0.2-0.65). CONCLUSION: This novel surgical technique for HSFs is a viable alternative to previously described methods with the advantage of being less prone to nerve injury and easy to fix distal extra-articular HSFs. The learning curve is short. LEVEL OF EVIDENCE: IV.

Medial minimally invasive plate osteosynthesis for humeral shaft fractures: a case series.

Minimally invasive plate osteosynthesis (MIPO) is increasingly favored for treating humeral shaft fractures (HSFs). However, conventional MIPO techniques pose challenges in fixing fractures near the fossa olecrani and carry a high risk of iatrogenic radial nerve palsy. This study was aimed to report the clinical outcomes of a series of patients who underwent MIPO through a medial approach for HSFs and describe our treatment algorithm. Patients and Method: This is a study conducted in our university hospital, which is a Level 1 academic trauma center. A retrospective analysis of 21 patients with HSFs who received minimally invasive treatment using plate osteosynthesis through a medial approach over a 5-year period was conducted. The outcomes measured included time for radiographic consolidation, disabilities of the arm, shoulder, and hand score, and complications such as infection, iatrogenic radial nerve injury, loss of reduction or fixation, and nonunion. Results: Twenty-one patients who underwent the procedure were identified. Bone healing was achieved in all patients with an early and aggressive range of motion. There were no cases of infection or iatrogenic radial nerve injury. The mean radiographic fracture union time was 15.76 weeks (range: 8-40 weeks). The mean disabilities of the arm, shoulder, and hand score was 3.29 (range: 0-14.17) at the time of the last follow-up. The mean screw density was 0.43. Conclusion: The proposed algorithm is effective in addressing the challenges of iatrogenic nerve injury and extra-articular distal fixation of HSFs with conventional MIPO techniques.

Pan-cancer analyses reveal the immunotherapeutic value of klotho.

Klotho (KL) was initially thought to be a typical "ageing suppressor" gene, but recent studies have suggested that KL is involved in the progression of several types of human cancer. This study aims to analyse whether the expression level of KL could impact patient prognosis, clinical parameters, and tumour immunity in different tumour patients. KL activity was utilized to determine differences between the KL transcript and KL protein. Expression levels were detected by single-sample gene enrichment analysis (GSEA). To explore the inherent mechanisms of KL in tumour immunotherapy, we investigated the possible impact of KL on the tumour microenvironment, immune processes and immune components. GO and KEGG analysis showed that KL was significantly involved in immune response, Inflammation, and calcium signaling pathway. We also found that KL was significantly correlated with multiple immunotherapeutic biomarkers (TMB, MSI, CD274, PDCD1, CTLA4 and TIGIT) in a variety of tumours. Furthermore, increased KL expression was closely associated with the non-response of anti-PD-1 immunotherapy, indicating that KL might affect the response sensitivity of tumour patients to anti-PD-1 immunotherapy. This study will provide a basis for further research on how KL regulates tumour immune cells and may lead to the development of more effective target tumour immunotherapy.

Self-Amplifying Iridium(III) Photosensitizer for Ferroptosis-Mediated Immunotherapy Against Transferrin Receptor-Overexpressing Cancer.

Photoimmunotherapy is attractive for cancer treatment due to its spatial controllability and sustained responses. This work presents a ferrocene-containing Ir(III) photosensitizer (IrFc1) that can bind with transferrin and be transported into triple-negative breast cancer (TNBC) cells via a transferrin receptor-mediated pathway. When the ferrocene in IrFc1 is oxidized by reactive oxygen species, its capability to photosensitize both type I (electron transfer) and type II (energy transfer) pathways is activated through a self-amplifying process. Upon irradiation, IrFc1 induces the generation of lipid oxidation to cause ferroptosis in TNBC cells, which promotes immunogenic cell death (ICD) under both normoxia and hypoxia. In vivo, IrFc1 treatment elicits a CD8+ T-cell response, which activates ICD in TNBC resulting in enhanced anticancer immunity. In summary, this work reports a small molecule-based photosensitizer with enhanced cancer immunotherapeutic properties by eliciting ferroptosis through a self-amplifying process.

Comprehensive analysis of hypoxia-related genes for prognosis value, immune status, and therapy in osteosarcoma patients.

Osteosarcoma is a common malignant bone tumor in children and adolescents. The overall survival of osteosarcoma patients is remarkably poor. Herein, we sought to establish a reliable risk prognostic model to predict the prognosis of osteosarcoma patients. Patients ' RNA expression and corresponding clinical data were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus databases. A consensus clustering was conducted to uncover novel molecular subgroups based on 200 hypoxia-linked genes. A hypoxia-risk models were established by Cox regression analysis coupled with LASSO regression. Functional enrichment analysis, including Gene Ontology annotation and KEGG pathway analysis, were conducted to determine the associated mechanisms. Moreover, we explored relationships between the risk scores and age, gender, tumor microenvironment, and drug sensitivity by correlation analysis. We identified two molecular subgroups with significantly different survival rates and developed a risk model based on 12 genes. Survival analysis indicated that the high-risk osteosarcoma patients likely have a poor prognosis. The area under the curve (AUC) value showed the validity of our risk scoring model, and the nomogram indicates the model's reliability. High-risk patients had lower Tfh cell infiltration and a lower stromal score. We determined the abnormal expression of three prognostic genes in osteosarcoma cells. Sunitinib can promote osteosarcoma cell apoptosis with down-regulation of KCNJ3 expression. In summary, the constructed hypoxia-related risk score model can assist clinicians during clinical practice for osteosarcoma prognosis management. Immune and drug sensitivity analysis can provide essential insights into subsequent mechanisms. KCNJ3 may be a valuable prognostic marker for osteosarcoma development.

Bone morphogenetic protein 9 is a potential tumor suppressor in osteosarcoma.

Transforming growth factor-ß (TGF-ß) is known to promote tumor migration and invasion. Bone morphogenetic proteins (BMPs) are members of the TGF-ß family expressed in a variety of human carcinoma cell lines. Although accumulating evidence has shown that BMP9 plays important roles in the regulation of various cellular processes, the function of BMP9 in clinical osteosarcoma remains to be explored. In this study, BMP9 expression was analyzed in 55 osteosarcoma patient samples and their matching, distant non-cancerous tissues. And the roles of BMP9 in osteosarcoma cell proliferation, apoptosis and cell cycle were also examined. Our results showed that different expression level of BMP9 was detected in all osteosarcoma samples while no expression in normal tissues. Surprisingly, there was a negative association between the expression level of BMP9 and osteosarcoma grade, with low level of BMP9 being found in high histological grade osteosarcoma. Knockdown of BMP9 accelerated the proliferation of MG63, SaOS-2, and U2OS cells. BMP9 overexpression, however, induced cell apoptosis in U2OS cells. Together, these results indicated that BMP9 plays a pivotal role in osteosarcoma. Future studies defining the mechanism of BMP9 effect may lead to novel therapeutic approaches for osteosarcoma.

Downregulated microRNA-26a modulates prostate cancer cell proliferation and apoptosis by targeting COX-2.

MicroRNA-26a (miR-26a) is expressed at lower levels in prostate cancer cells compared with normal prostate cells. However, the regulatory mechanism of miR-26a in tumorigenesis and metastasis is not clear. In the present study, the expression profile of cellular miR-26a was analyzed by reverse transcription-quantitative polymerase chain reaction. The potential target of miR-26a was identified by luciferase assay and western blotting. Examination of miR-26a function was performed by transfection with miR-26a mimics and inhibitor. It was found that miR-26a expression was decreased in prostate cancer tissues and cell lines, with androgen-independent prostate cancer (AIPC) showing lower miR-26a expression compared with androgen-dependent prostate cancer (ADPC). Overexpression of miR-26a by transfecting miR-26a mimics could significantly enhance apoptosis, and this upregulation of apoptosis was triggered by cytochrome c oxidase subunit II inhibition. Furthermore, it was found that lower miR-26a density resulted in an evidently poor prognosis. Understanding the important roles of miR-26a in regulating cell apoptosis in human prostate cancer cells may aid the exploration of AIPC transformation mechanisms and contribute to the development of miRNA-based therapy in the future.