Comprehensive investigation of tumor immune microenvironment and prognostic biomarkers in osteosarcoma through integrated bulk and single-cell transcriptomic analysis.

Osteosarcoma (OS) is an aggressive and highly lethal bone tumor, highlighting the urgent need for further exploration of its underlying mechanisms. In this study, we conducted analyses utilizing bulk transcriptome sequencing data of OS and healthy control samples, as well as single cell sequencing data, obtained from public databases. Initially, we evaluated the differential expression of four tumor microenvironment (TME)-related gene sets between tumor and control groups. Subsequently, unsupervised clustering analysis of tumor tissues identified two significantly distinct clusters. We calculated the differential scores of the four TME-related gene sets for Clusters 1 (C1) and 2 (C2), using Gene Set Variation Analysis (GSVA, followed by single-variable Cox analysis. For the two clusters, we performed survival analysis, examined disparities in clinical-pathological distribution, analyzed immune cell infiltration and immune evasion prediction, assessed differences in immune infiltration abundance, and evaluated drug sensitivity. Differentially expressed genes (DEGs) between the two clusters were subjected to Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA). We conducted Weighted Gene Co-expression Network Analysis (WGCNA) on the TARGET-OS dataset to identify key genes, followed by GO enrichment analysis. Using LASSO and multiple regression analysis we conducted a prognostic model comprising eleven genes (ALOX5AP, CD37, BIN2, C3AR1, HCLS1, ACSL5, CD209, FCGR2A, CORO1A, CD74, CD163) demonstrating favorable diagnostic efficacy and prognostic potential in both training and validation cohorts. Using the model, we conducted further immune, drug sensitivity and enrichment analysis. We performed dimensionality reduction and annotation of cell subpopulations in single cell sequencing analysis, with expression profiles of relevant genes in each subpopulation analyzed. We further substantiated the role of ACSL5 in OS through a variety of wet lab experiments. Our study provides new insights and theoretical foundations for the prognosis, treatment, and drug development for OS patients.

Enhanced nerve function recovery in radial nerve palsy patients with humerus shaft fracture: a randomized study of low-frequency pulse electrical stimulation combined with exercise therapy.

Objective: To evaluate the effect of low-frequency pulse electrical stimulation plus exercise therapy on nerve function recovery in patients with radial nerve palsy after humerus shaft fracture. Methods: A total of 110 patients with humerus shaft fracture and radial nerve injury admitted to our hospital from January 2017 to December 2021 were recruited. They were randomized to receive either conventional exercise therapy (control group) or conventional exercise therapy plus low-frequency pulse electrical stimulation (study group) according to the random number table method, with 55 cases in each. Clinical efficacy, muscle strength recovery, nerve conduction velocity (MCV), amplitude, wrist joint, and elbow joint activities of patients were analyzed and compared. Results: Patients with low frequency stimulation (LFS) showed significantly higher treatment effectiveness (89.09%) than those with exercise therapy only (69.09%). The incorporation of LFS with exercise therapy provided more enhancement in the muscle strength of wrist extensor and total finger extensor in patients when compared with a mere exercise intervention, suggesting better muscle function recovery of patients produced by LFS. Moreover, a significant increase in MCV and its amplitude was observed in all included patients, among which those receiving LFS showed a greater escalation of MCV and its amplitude. Following a treatment duration of 6 months, more patients in the LFS cohort were reported to achieve a wrist extension and elbow extension with an angle over 45° than the controls. There was no notable variance in adverse responses noted between the two patient groups. Conclusion: In patients afflicted with humerus shaft fracture and radial nerve injury, the amalgamation of exercise therapy with low-frequency pulse electrical stimulation can significantly improve clinical efficacy, promote nerve function, and muscle strength recovery, and features a high safety profile. Relevance to clinical practice: The combination of exercise therapy and low-frequency pulsed electrical stimulation can notably improve the promotion of neurologic function and muscle strength recovery in patients with humerus shaft fractures and radial nerve injuries with a high degree of safety.Clinical trial registration:https://www.researchregistry.com, identifier researchregistry9461.

Surgical Reconstruction of Type IV Hypoplasia of the Thumb (Floating Thumb) in Infants: A Retrospective Analysis of Functional Outcomes and Radiographic Alignment.

BACKGROUND Congenital hypoplasia of the thumb type IV, also known as floating thumb, is a condition in which 2 small phalanges are attached to the hand with a thin skin bridge. Surgical management options for this condition vary from amputation to flap reconstruction. MATERIAL AND METHODS This retrospective study analyzed 11 infants with congenital hypoplasia of the thumb type IV who underwent surgical reconstruction using a modified vascularized polydactylous hallux flap. The study included 6 male and 5 female infants, aged 6 to 24 months. Functional evaluations and radiographic studies were conducted postoperatively. RESULTS All 11 patients underwent the complete surgical protocol. Successful vascular and nerve anastomoses were performed during the initial procedure, ensuring sufficient blood supply and neural connectivity to the transferred toes. The second operation showed promising outcomes, including improvements in thumb opposition, grasp strength, and overall function. Postoperative assessments demonstrated satisfactory radiographic alignment and no major complications during the follow-up period. CONCLUSIONS The modified vascularized polydactylous hallux flap reconstruction is a viable surgical option for managing congenital hypoplasia of the thumb type IV in infants. This technique effectively restores thumb opposition, grasp strength, and overall hand function, with satisfactory radiographic alignment and minimal complications. The study findings support the efficacy and safety of this surgical approach in addressing this rare congenital anomaly.

Targeted delivery of anti-osteoporosis therapy: Bisphosphonate-modified nanosystems and composites.

Osteoporosis (OP) constitutes a significant health concern that profoundly affects individuals' quality of life. Bisphosphonates, conventional pharmaceuticals widely employed in OP treatment, encounter limitations related to inadequate drug targeting and a short effective duration, thereby compromising their clinical efficacy. The burgeoning field of nanotechnology has witnessed the development and application of diverse functional nanosystems designed for OP treatment. Owing to the bone tissue affinity of bisphosphonates, these nanosystems are modified to address shortcomings associated with traditional drug delivery. In this review, we explore the potential of bisphosphonate-modified nanosystems as a promising strategy for addressing osteoporotic conditions. With functional modification, these nanosystems exhibit a targeted and reversible effect on osteoporotic remodeling, presenting a promising solution to enhance precision in drug delivery. The synthesis methods, physicochemical properties, and in vitro/in vivo performance of bisphosphonate-modified nanosystems are comprehensively examined in this review. Through a thorough analysis of recent advances and accomplishments in this field, we aim to provide insights into the potential applications and future directions of bisphosphonate-modified nanosystems for targeted and reversible osteoporotic remodeling.

A prospective observational study comparing outcomes application of low-frequency pulse electrical combined with target-oriented rehabilitation therapy in postoperative nerve function rehabilitation of patients with distal humeral fracture and radial nerve injury.

Objective: The aim of the present study was to compare the effect of low-frequency pulse electrical stimulation combined with target-oriented rehabilitation therapy and single low-frequency pulse electrical stimulation therapy on postoperative neurological improvement in patients with radial nerve injury and humeral condylar fracture. Methods: A total of 88 patients with humeral condyle fracture and radial nerve injury admitted to our hospital from April 2019 to January 2022 were randomly divided into a combined group and a control group, with 44 patients in each group. The patients in the combined group received low-frequency pulse electrical stimulation combined with target-oriented rehabilitation therapy, while those in the control group received low-frequency pulse electrical stimulation therapy. The recovery rate of radial nerve function, the recovery of finger extensor and wrist extensor muscle strength, and the occurrence of postoperative complications were evaluated in all patients. Results: After treatment, the recovery rate in the combined group (77.27%) was higher than that in the control group (50.00%) (p < 0.05). There was no significant difference in finger extensor and wrist extensor muscle strength before treatment between the two groups (p > 0.05). After treatment, both groups showed improvement compared to before treatment (p < 0.05), and the recovery in the combined group was better than that in the control group (p < 0.05). There was no significant difference in MCV and amplitude before treatment between the two groups (p > 0.05). After treatment, both groups showed improvement compared to before treatment (p < 0.05), and the recovery in the combined group was better than that in the control group (p < 0.05). The fracture healing time in the combined group was shorter than that in the control group (p < 0.05). During the treatment period, there was one case of infection and one case of joint pain in the combined group, with a complication rate of 4.55%. In the control group, there was one case of infection and two cases of joint pain, with a complication rate of 6.82%. There was no significant difference in the complication rate between the two groups (p > 0.05). The DHI score in the combined group was better than that in the control group (p < 0.05). The ESCA score in the combined group was better than that in the control group (p < 0.05). Conclusion: Low-frequency pulse electrical stimulation combined with target-oriented rehabilitation therapy can promote muscle strength and functional recovery after radial nerve injury, accelerate fracture healing time, and no additional risk of complications. Clinical trial registration: https://www.researchregistry.com/, researchregistry9461.

Nanoparticle-Facilitated Therapy: Advancing Tools in Peripheral Nerve Regeneration.

Peripheral nerve injuries, arising from a diverse range of etiologies such as trauma and underlying medical conditions, pose substantial challenges in both clinical management and subsequent restoration of functional capacity. Addressing these challenges, nanoparticles have emerged as a promising therapeutic modality poised to augment the process of peripheral nerve regeneration. However, a comprehensive elucidation of the complicated mechanistic foundations responsible for the favorable effects of nanoparticle-based therapy on nerve regeneration remains imperative. This review aims to scrutinize the potential of nanoparticles as innovative therapeutic carriers for promoting peripheral nerve repair. This review encompasses an in-depth exploration of the classifications and synthesis methodologies associated with nanoparticles. Additionally, we discuss and summarize the multifaceted roles that nanoparticles play, including neuroprotection, facilitation of axonal growth, and efficient drug delivery mechanisms. Furthermore, we present essential considerations and highlight the potential synergies of integrating nanoparticles with emerging technologies. Through this comprehensive review, we highlight the indispensable role of nanoparticles in propelling advancements in peripheral nerve regeneration.

Artificial neural network-based gene screening and immune cell infiltration analysis of osteosarcoma feature.

BACKGROUND: The present study aimed to construct an artificial neural network (ANN) model that leverages characteristic genes associated with osteosarcoma (OS) to enable accurate prognostication for OS patients. METHODS: Our research revealed 467 differentially expressed genes (DEGs) via gene expression contrast analysis, consisting of 345 downregulated genes and 122 upregulated genes. Gene Ontology (GO) enrichment analysis illuminated functions primarily encompassing T-cell activation, secretory granule lumen and antioxidant activity, among others. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, we discovered significant correlations between the DEGs and certain pathways, including phagosome, Staphylococcus aureus infection and human T-cell leukemia virus 1 infection. We then screened out 30 characteristic DEGs (CDEGs) based on random forest analysis and constructed the ANN model using the gene score matrix. To verify the credibility and accuracy of the ANN model, we performed internal and external validation processes, which affirmed our model's predictive capabilities. RESULTS: The study further delved into the analysis of immune cell infiltration and its correlation with the target CDEGs, revealing disparities in the infiltration of 22 types of immune cells across different groups and their interrelationships. Moreover, we probed the expression of the two foremost CDEGs (YES1 and MFNG) in OS and normal tissues. We noted a positive relationship between the expression of YES1 and MFNG in OS tissues and the clinicopathological characteristics of OS patients. CONCLUSIONS: Collectively, the findings of the present study validate the effectiveness of the CDEGs-based ANN model in predicting OS patients, which might facilitate early diagnosis and treatment of OS.

How Advancing is Peripheral Nerve Regeneration Using Nanofiber Scaffolds? A Comprehensive Review of the Literature.

Peripheral nerve injuries present significant challenges in regenerative medicine, primarily due to inherent limitations in the body's natural healing processes. In response to these challenges and with the aim of enhancing peripheral nerve regeneration, nanofiber scaffolds have emerged as a promising and advanced intervention. However, a deeper understanding of the underlying mechanistic foundations that drive the favorable contributions of nanofiber scaffolds to nerve regeneration is essential. In this comprehensive review, we make an exploration of the latent potential of nanofiber scaffolds in augmenting peripheral nerve regeneration. This exploration includes a detailed introduction to the fabrication methods of nanofibers, an analysis of the intricate interactions between these scaffolds and cellular entities, an examination of strategies related to the controlled release of bioactive agents, an assessment of the prospects for clinical translation, an exploration of emerging trends, and thorough considerations regarding biocompatibility and safety. By comprehensively elucidating the intricate structural attributes and multifaceted functional capacities inherent in nanofiber scaffolds, we aim to offer a prospective and effective strategy for the treatment of peripheral nerve injury.

Comprehensive bioinformatics analysis reveals the oncogenic role of FoxM1 and its impact on prognosis, immune microenvironment, and drug sensitivity in osteosarcoma.

Osteosarcoma, a highly malignant bone tumor primarily affecting adolescents, presents a significant challenge in cancer therapy due to its resistance to chemotherapy. This study explores the multifaceted impact of the transcription factor FoxM1 on osteosarcoma, shedding light on its pivotal role in tumor progression, immune microenvironment modulation, and drug response. Utilizing publicly available datasets from the Gene Expression Omnibus (GEO) and Therapeutically Applicable Research To Generate Effective Treatments (TARGET) databases, we conducted an in-depth bioinformatics analysis. Our findings illuminate the far-reaching implications of FoxM1 in osteosarcoma, emphasizing its significance as a potential therapeutic target. Differential expression analysis and Gene Set Enrichment Analysis (GSEA) revealed FoxM1's influence on critical pathways related to apoptosis, cell cycle regulation, and DNA repair. Notably, FoxM1 expression correlated with poor clinical outcomes in osteosarcoma patients, highlighting its prognostic relevance. Additionally, FoxM1 was found to modulate the immune microenvironment within tumor tissues, impacting immune cell infiltration, immunomodulators, immune checkpoints, and chemokines. Furthermore, a prognostic model based on FoxM1-coexpressed genes demonstrated its effectiveness in predicting patient survival. Drug sensitivity analysis indicated FoxM1's association with drug response, potentially guiding personalized treatment approaches. Hub gene screening identified RAB23 as a key target regulated by FoxM1, with RAB23 shown to influence osteosarcoma cell growth. This study also confirmed FoxM1's overexpression in osteosarcoma tissues compared to normal tissues, and its association with clinicopathological characteristics, including clinical stage, pathological type, and lung metastasis. In conclusion, FoxM1 emerges as a central player in the pathogenesis of osteosarcoma, impacting gene expression, immune responses, and therapeutic outcomes. This comprehensive analysis deepens our understanding of FoxM1's role in osteosarcoma and offers potential avenues for improved diagnosis and treatment.

A comprehensive analysis of G-protein-signaling modulator 2 as a prognostic and diagnostic marker for pan-cancer.

Background: G-protein signaling modulator 2 (GPSM2) maintains cell polarization and regulates the cell cycle. Recent studies have shown that it is highly expressed in various tumors, but its pan-cancer analysis has not been reported. Methods: First, we analyzed the differential GPSM2 expression in normal and cancer tissues by the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Human Protein Atlas databases and investigated its expression effect on the survival of cancer patients by gene expression profiling interactive analysis 2 (GEPIA2). Second, we analyzed the GPSM2 phosphorylation level using the clinical proteomic tumor analysis consortium dataset. In addition, we investigated GPSM2 gene mutations in human tumor specimens and the impact of gene mutations on patient survival. Finally, we analyzed the relationship between GPSM2 expression and cellular immune infiltration through the TIMER 2.0 database. Meanwhile, the possible signaling pathway of the gene was analyzed by the Gene Ontology (GO)| Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway to explore its potential mechanism. Results: GPSM2 is overexpressed in most cancers, which leads to reduced overall survival (OS) and disease-free survival in patients. The results of phosphorylation analysis suggest that tumor development involves a complex GPSM2 phosphorylation process. We identified GPSM2 mutation loci with the highest frequency of mutations in uterine corpus endometrial carcinoma (UCEC), and this mutation increased progression-free survival and overall survival in uterine corpus endometrial carcinoma patients. Finally, we found that the role of GPSM2 in tumors may be associated with cellular immune infiltration. Gene Ontology|KEGG pathway analysis showed that the enrichment pathways were mainly "mitotic nuclear division," "chromosome segregation," and "spindle." Conclusions: Our pan-cancer analysis provides a comprehensive overview of the oncogenic roles and potential mechanisms of GPSM2 in multiple human cancers.

Integrated analysis of anti-tumor roles of BAP1 in osteosarcoma.

Background: This study aims to screen out differentially expressed genes (DEGs) regulated by BRCA1-associated protein 1 (BAP1) in osteosarcoma cells, and to analyze their biological functions. Methods: The microarray dataset GSE23035 of BAP1-knockdown osteosarcoma cells was obtained from Gene Expression Omnibus (GEO) database, consisting of shControl, shBAP1#1 and shBAP1#2 samples. The DEGs between the BAP1-knockdown osteosarcoma cells and the untreated osteosarcoma cells were screened with limma package, and then subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Gene Set Enrichment Analysis (GSEA) was also performed for the three groups of samples. Hub genes in a protein-protein interaction (PPI) network of DEGs was filtered, and then subjected to prognostic analysis and correlation analysis with BAP1 in Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Besides, the correlation between BAP1 and biological processes/pathways was analyzed by Gene Set Variation Analysis (GSVA) method and the correlation between BAP1 and immune infiltration by CIBERSORT and ESTIMATE methods. The roles of BAP1 in regulating proliferation and epithelial-mesenchymal transition (EMT) were validated by CCK-8 and western blot. Results: 58 upregulated DEGs and 81 downregulated DEGs were obtained with |logFC| ≥ 1 and adj.p < 0.05. Cell cycle, DNA repair, and focal adhesion were associated with BAP1 in datasets. Further, BAP1 was negatively correlated with naïve CD4 T cells infiltration. In vitro, BAP1 inhibited proliferation and EMT. Conclusion: BAP1 might be a tumor suppressor in osteosarcoma and a promising therapeutic target.

Bone Cement-Augmented Short-Segment Pedicle Screw Fixation for Kümmell Disease with Spinal Canal Stenosis.

BACKGROUND This study aimed to explore the feasibility and efficacy of bone cement-augmented short-segmental pedicle screw fixation in treating Kümmell disease. MATERIAL AND METHODS From June 2012 to June 2015, 18 patients with Kümmell disease with spinal canal stenosis were enrolled in this study. Each patient was treated with bone cement-augmented short-segment fixation and posterolateral bone grafting, and posterior decompression was performed when needed. All patients were followed up for 12-36 months. We retrospectively reviewed outcomes, including the Oswestry disability index (ODI), visual analog scale (VAS) score, anterior and posterior heights of fractured vertebrae, kyphotic Cobb angle, and neurological function by Frankel classification. RESULTS The VAS grades, ODI scores, anterior heights of affected vertebrae, and kyphotic Cobb angles showed statistically significant differences between pre- and postoperative and between preoperative and final follow-up values (P<0.05), whereas the differences between postoperative and final follow-up values were not statistically significant (P>0.05). The differences between posterior vertebral heights at each time point were not statistically significant (P>0.05). Improved neurological function was observed in 12 cases at final follow-up. Three cases had complications, including asymptomatic cement leakage in 2 patients and delayed wound infection in 1 patient. CONCLUSIONS Bone cement-augmented short-segment pedicle screw fixation is safe and effective for treating Kümmell disease, and can achieve satisfactory correction of kyphosis and vertebral height, with pain relief and improvement in neurological function, with few complications.

[Causes prevention and treatment for cerebrospinal leak after lumbar revision surgery].

OBJECTIVE: To analyze the causes and explore the measures of prevention and treatment of the cerebrospinal leak after lumbar revision surgery. METHODS: The clinical data of 24 patients(17.78%) with cerebrospinal leak among 135 cases after lumbar revision surgery from January 2011 to January 2016 was retrospectively studied. Of them, 12 cases due to severe adhesion caused by scar formation; 4 cases due to yellow ligament hyperplasia adhesion with dura mater occurred dural tears when separating adhesion; 2 cases with severe hyperplasia and ossification of lumbar posterior longitudinal ligament occurred dural tears when revealing intervertebral disk; 2 cases due to improper nailing happened dural tears during operation. And the other 4 cases without obvious dural tears in surgery, occurred cerebrospinal leak one to two days after surgery. And the 24 patients were treated with the measures of prevention and treatment preoperatively, intraoperatively, and postoperatively. RESULTS: Twenty-four patients with cerebrospinal leak were cured after treatment and were follow-up for 6 to 30 months. No recurrence of cerebrospinal leake or local and systemic complications were found. CONCLUSIONS: Scar formation is the main cause of cerebrospinal leak in lumbar revision surgery. As for lumbar revision surgery, as long as the standard control measures are taken, it can significantly reduce the incidence of cerebrospinal leak, achieve better clinical efficacy, and fundamentally solve the cerebrospinal leak problem that has plagued both doctors and patients for a long time.

[Therapeutic progress in lumbar spinal stenosis].

Along with the population aging in China, patients with lumbar spinal stenosis(LSS) caused by recessive change incessantly increase. At present, there is no adequate evidence to recommend any specific nonoperative treatment for LSS, and surgery is still an effective method. The cilincal symptoms of the patients without conservative treatment got improvement after surgery, which is the strongest evidence base. Spinal instability after simple decompression promotes the development of fusion technique, and the accelerated adjacent segment degeneration and no relief in symptoms after fusion lead to dynamic fixation technology emerge as the times require. Patients with spinal canal decompression whether need bone fusion or not is still controversial. For the past few years, the operation of simple decompression for LSS obviously decreased, whereas the decompression plus fusion surgery showed sustainable growth. Decompression complicated with fusion was more and more adopted in LSS, in order to reduce the hidden risk of spinal instability and deformity. Although decompressive operation has determinate effect, now it is still unclear if the therapeutic effect of decompression complicated with fusion is better than simple decompression. This article reviews the current studies to explore whether decompression plus bone fusion is applicable for LSS. To further explore the best choice of surgical treatment for LSS, we focused on evidence-based therapeutic options.

[POSTEROLATERAL FUSION AND PEDICLE SCREW FIXATION FOR TREATING OLD THORACOLUMBAR FRACTURE COMBINED WITH KYPHOSIS IN ELDERLY PATIENTS].

OBJECTIVE: To investigate the clinical efficacy and the indications of posterolateral fusion and pedicle screw short-segment fixation via injured vertebra for treating old thoracolumbar fracture combined with kyphosis in elderly patients. METHODS: Between January 2012 and December 2014, 24 patients with old thoracolumbar fracture and kyphosis received posterolateral fusion and pedicle screw short-segment fixation via injured vertebra. Of 24 cases, 8 were male and 16 were female with an average age of 66.3 years (range, 56-79 years). The mean disease course was 17.5 months (range, 5-36 months). There were 13 cases of osteoporosis, 9 cases of osteopenia, and 2 cases of normal bone. The visual analogue scale (VAS) was 6.53±0.95, and Oswestry disability index (ODI) was 52.63%±5.74% preoperatively. The thoracolumbar kyphosis located at T10 to L2, and the kyphotic Cobb angle was (28.79±5.04)° before operation. RESULTS: The operation was completed successfully without related complications. The operative time was 1.2-2.3 hours (mean, 1.6 hours), and intraoperative blood loss was 80-210 mL (mean, 158 mL). No nerve injury occurred. Poor healing of incision was observed in 1 patient with diabetes, and primary healing of incision was obtained in the other patients. Nineteen patients were followed up 6-30 months (mean, 14.4 months), and there were 2 deaths. Pain relief and function recovery were obtained in 19 patients after operation. The VAS score and ODI were significantly decreased to 2.4±0.7 and 32.14%±5.12% at last follow-up (t=8.542, P=0.000; t=9.826, P=0.000). The kyphotic Cobb angle was significantly decreased to (21.23±4.30)° at immediate after operation (P<0.05) and to (23.68±4.35)° at last follow-up (P<0.05), but no significant difference was found between at immediate and last follow-up (P>0.05). No loosening or breakage of internal fixation was observed during follow-up. CONCLUSIONS: Posterolateral fusion and pedicle screw short-segment fixation via injured vertebra is a safe and effective treatment for elderly patients with old thoracolumbar fracture combined with kyphosis (Cobb angle less than 40°).