Development and validation of a nomogram for predicting the prognosis in children with spinal cord injuries.

AIMS: This research aims to construct and verify an accurate nomogram for forecasting the 3-, 5-, and 7-year outcomes in pediatric patients afflicted with spinal cord injury (SCI). METHODS: Pediatric patients with SCI from multiple hospitals in China, diagnosed between Jan 2005 and Jan 2020, were incorporated into this research. Half of these patients were arbitrarily chosen for training sets, and the other half were designated for external validation sets. The Cox hazard model was employed to pinpoint potential prognosis determinants related to the American Spinal Injury Association (ASIA) and Functional Independence Assessment (FIM) index. These determinants were then employed to formulate the prognostic nomogram. Subsequently, the bootstrap technique was applied to validate the derived model internally. RESULTS: In total, 224 children with SCI were considered for the final evaluation, having a median monitoring duration of 68.0 months. The predictive nomogram showcased superior differentiation capabilities, yielding a refined C-index of 0.924 (95% CI: 0.883-0.965) for the training cohort and a C-index of 0.863 (95% CI: 0.735-0.933) for the external verification group. Additionally, when applying the aforementioned model to prognostic predictions as classified by the FIM, it demonstrated a high predictive value with a C-index of 0.908 (95% CI: 0.863-0.953). Moreover, the calibration diagrams indicated a consistent match between the projected and genuine ASIA outcomes across both sets. CONCLUSION: The crafted and verified prognostic nomogram emerges as a dependable instrument to foresee the 3-, 5-, and 7-year ASIA and FIM outcomes for children suffering from SCI.

A nomogram for predicting the hospital-acquired infections in children with spinal cord injuries: a retrospective, multicenter, observational study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Hospital-acquired infections (HAIs) pose a significant risk for pediatric patients with spinal cord injuries (SCIs), potentially leading to extended hospital stays and increased morbidity. This study aims to identify patients at higher risk for HAIs. SETTING: Hospitals from multiple areas in China. METHODS: This retrospective study included 220 pediatric SCI patients from Jan 2005 to Dec 2023, divided into a training set (n = 154) and a validation set (n = 66). We conducted a multivariate logistic regression analysis to identify risk factors associated with HAIs and constructed a predictive nomogram. The model's performance was assessed using receiver operating characteristic (ROC) curves, area under the ROC curve (AUC) and calibration plots, while decision curve analysis was utilized to determine clinical utility. RESULTS: The nomogram incorporated age, time from injury to the hospital, history of urinary and pulmonary infections, urobilinogen positivity, damaged segments, and admission American Spinal Injury Association (ASIA) scores. The model demonstrated excellent discrimination in the training set (AUC = 0.957) and good discrimination in the validation set (AUC = 0.919). Calibration plots indicated an acceptable fit between predicted probabilities and observed outcomes. Decision curve analysis confirmed the model's net benefit over clinical decision thresholds in both sets. CONCLUSION: We developed and validated a predictive nomogram for HAIs in pediatric SCI patients that shows promise for clinical application. The model can assist healthcare providers in identifying patients at higher risk for HAIs, potentially facilitating early interventions and improved patient care strategies.

Platelet-Rich Plasma Promotes Spinal Ligament Healing after Injury.

BACKGROUND: Spinal ligament injury is often a comorbidity in spine fracture. Although the spinal ligament is important to maintain spinal stability, little is done to improve its healing after injury. Platelet-rich plasma (PRP) has been shown effective in treating many tendon and ligament disorders, but its role in spinal ligament injury remains to be evaluated. METHODS: Supraspinous ligament and interspinous ligament were cut in rabbits to simulate spinal ligament injury after spine fracture. After the injury, the administration of autologous PRP was performed and compared with saline injection control. Morphology and histological analysis were utilized to assess PRP effect and compare it to the saline control group. To understand potential molecular mechanisms of PRP on ligamentous healing, bioinfor-matics analysis of the microarray dataset (GSE70918) from the Gene Expression Omnibus database was conducted. RESULTS: The PRP group was more likely to have a better appearance both morphologically and histologically than did the saline control group. Pathway analysis determined that IL-17 signaling pathway and TNF signaling pathway were the two significantly induced signaling pathways in tendon fibroblasts treated by PRP. In the protein-protein interaction network analysis, interleukin 6 had the highest degrees of connectivity. CONCLUSIONS: PRP improves spinal ligament healing through the activation of pathways related to inflammation. Further studies are required to determine the dosing and timing of PRP administration to achieve better longterm treatment outcome.

Serum Calcium is Related to the Degree of Artery Stenosis in Acute Ischemic Stroke.

BACKGROUND/AIMS: Acute ischemic stroke is caused by stenosis of artery supplying to brain. We aimed to detect some metabolites in the serum that would be related to the degree of artery stenosis and to analyze potential mechanisms. METHODS: Patients diagnosed with acute ischemic stroke were divided into two groups according to their degree of artery stenosis (which was determined by computed tomographic angiography): a mild group (stenosis ≤ 30%) and a severe group (stenosis > 30%). Serum from these patients was collected, and we focused on the differences in the concentrations of calcium, uric acid, low density lipoprotein and homocysteine. The dataset GSE11583 from the Gene Expression Omnibus database was analyzed to find the potential mechanism using bioinformatics methods. RESULTS: Among the four metabolites, the only difference that reached significance between the two groups was in the concentration of calcium in serum (2.27±0.08 mmol/L vs 2.21±0.08 mmol/L). By comparing the gene expression levels between normal endothelial cells and adaptive remodeling endothelial cells in GSE11583, we identified 51 upregulated and 40 downregulated genes in adaptive remodeling endothelial cells. The gene set enrichment analysis revealed that upregulated genes were enriched in a phosphatidylinositol signaling system, which is closely involved in the calcium signaling pathway. CONCLUSION: Our results suggest that the concentration of serum calcium is higher in patients with more severe artery stenosis lesions and that the phosphatidylinositol signaling system is a key biological pathway involved in this process.

Characteristics of cervical sagittal parameters in healthy cervical spine adults and patients with cervical disc degeneration.

BACKGROUND: The cervical sagittal parameters of the normal population and the impact of disc degeneration on cervical sagittal alignment have not been clearly defined yet. This study is applied to investigate the characteristics and relationships of cervical sagittal parameters in normal adults and patients with cervical disc degeneration. METHODS: We reviewed 50 normal control subjects (normal group, NG) and 50 patients with cervical disc degeneration (degeneration group, DG), who had both cervical MRI and radiographs obtained together, between January 2010 and September 2015. Data including C2-7 lordosis (CL), T1 slope (T1S), thoracic inlet angle (TIA), neck tilt (NT), C2-7 sagittal vertical axis (C2-7 SVA), cervical tilting, and cranial tilting on cervical radiographs were collected and analyzed. RESULTS: T1S in the NG was significantly greater than in the DG (P < 0.05), while NT and C2-7 SVA in the NG were significantly lower than in the DG (P < 0.01 and P < 0.05, respectively). T1S positively correlated with CL in both groups (Pearson correlation coefficients of 0.588 in the NG and 0.504 in the DG). No significant difference was seen in TIA between the NG and DG. CONCLUSIONS: T1S was involved in the occurrence and development of cervical disc degeneration, and TIA could be considered as a constant morphological parameter in both the normal population and cervical disc degeneration patients.

Surgical Landmark of Mandible Angle in the Identification of Cervical Spinal Level.

Mandible angle is considered to be a consistently palpable external landmark for the identification of cervical spinal level by a radiographic study. But this anatomical study aimed to determine the positional relationship between mandible angle and cervical spinal level in cadavers. In this study, the cervical spine of 10 adult cadavers with intact head and neck structure, including 6 males and 4 females, was dissected, and the position of mandible angle (MA) relative to the corresponding cervical spinal level was measured when the head was fixed in the flexion, anatomy position, and extension. The difference between the genders and the sides was analyzed. On the basis of the study of the corpse samples, the reference level of cervical spine was approximated to C2/3 intervertebral disc. The result has confirmed MA as a consistent and convenient landmark in the identification of cervical spinal level. Given some external landmarks do not consistently correspond to the exact level of the cervical spine, MA provides the relatively consistent reference point: C2/3 intervertebral disc. The authors hold that MA is a superior external landmark, which can help surgeons to localize the skin incision before anterior cervical spine surgery.

Anterior transpedicular screws in conjunction with plate fixation and fusion for the treatment of subaxial cervical spine diseases.

OBJECTIVE: This study aimed at exploring the clinical application of anterior transpedicular screw (ATPS) and plate in the reconstruction of subaxial cervical spine. METHODS: 8 cases were reconstructed by ATPS and plate in the subaxial cervical spine from Jan 2009 to Dec 2011. X-rays and computed tomography images were collected to evaluate the position of ATPS. Magnetic resonance imaging was also included to evaluate the result of decompression, the existence of epidural hematoma and the morphology of the cervical spinal cord. Japanese Orthopaedic Association scores were observed before and after operation as a functional estimation. RESULTS: All of the eight cases were followed up from 3 to 36 months with the average of 15.5 months. A total of 16 ATPS were implanted in the subaxial cervical spine in the eight patients. All the screws were inserted smoothly. Bone fusion was found in all the subjects 4.5 months after operation on average. No loosening or breakage of the internal fixation was observed in our study. Hoarseness was observed in one case due to distraction injury of the recurrent laryngeal nerve, which disappeared after 3 weeks' conservative treatment. Dysphagia was complained by two patients after surgery, which was alleviated 3 months later. There were four screws deviating less than 1 mm (Grade 1), two medially and two laterally. All the anterior compressions were removed completely in this group. Only a small amount of epidural hematoma was found in four cases on MRI images before discharge. The average JOA scores were significantly improved from 5.6 ± 1.4 before surgery to 14.5 ± 0.8 at discharge (P < 0.01), which decreased to 13.2 ± 1.2 at 3 months after operation, but improved again to 15.2 ± 0.8 at 1 year after operation. CONCLUSION: Although there are some complications, ATPS with plate is an effective and safe technique for anterior reconstruction in the subaxial cervical spine. Only those spine centers with sufficient experience in complex cervical spine reconstruction surgery can conduct this technique according to strict indications.

[Three-dimensional finite-element study on anterior transpedicular screw fixation system of the subaxial cervical spine].

OBJECTIVE: To evaluate the biomechanical effects of the anterior cervical transpedicular-screw system (ACTPS), compared to the anterior cervical screw plate system (ACLP), in the subaxial cervical spine after 2-level corpectomy. METHODS: A verified intact finite element subaxial cervical (C3-C7) model was established and analyzed by Mimics 10.0, Rapidform XOR3, Hypermesh 10.0, CATIA5V19, ANSYS 14.0 softwares based on the CT data (C1-T1) was collected from a 28 years old male volunteer. The axial force of 75 N and moment couple of 1N·m was loaded on the upper surface of C3, which made the model movement in flexion extension, lateral bending, rotating direction, respectively. Then, recorded the range of motion, and compared the results with the in vitro biomechanical experimental data to verify the effectiveness of the model. The ACTPS model and the ACLP model were analyzed using the finite element method. The range of motion at the operation segments (C4-C7), the range of motion at the adjacent segment (C3-C4) and stress distribution under flexion, extension, lateral bending, and axial rotation were calculated, and compared the range of motion with intact model. RESULTS: There were 85,832 elements and 23,612 nodes in the intact model of subaxial cervical spine (C3-C7) in this experiment,and the range of motion of intact model validated with the reported cadaveric experimental data. In ACTPS group the stress was been well-distributed, but the stress concentrated on the interface between screw and the titanium plate in ACLP group. There were obvious differences of the maximum stress value between the two groups. The range of motion of fixed segments in ACTPS group was smaller than ACLP group, however adjacent segment range of motion showed no significant difference. Compared with the intact group, the range of motion in flexion extension, lateral flexion, rotation direction was decreased respectively about 25°, 20° and 8°, the range of motion at adjacent segment (C3-C4) was correspondingly compensated about 0.3°, 3° and 0.1°. CONCLUSIONS: ACTPS is better than ACLP in terms of biomechanical properties. It offers rigid stability, and may be more suitable for reconstruction stability of 2-level and more than 2 levels corpectomy in the subaxial cervical spine. Meanwhile, the risk of fracture of ACTPS system is lower than that of the ACLP system.

Investigation of the causal relationship between osteocalcin and dementia: A Mendelian randomization study.

Objective: Basic medical studies have reported an improved effect of osteocalcin on cognition. We explored the causal link between osteocalcin and dementia via the implementation of Mendelian randomization methodology. Methods: Genome-wide association studies were employed to identify single nucleotide polymorphisms (SNPs) showing significant correlations with osteocalcin. Subsequently, A two-sample Mendelian randomization analysis was conducted utilizing the inverse-variance-weighted (IVW) technique to assess the causal relationship between osteocalcin and various types of dementia, including Alzheimer's disease (AD), Parkinson's disease (PD), Lewy body dementia (LBD), and vascular dementia (VD). This approach aimed to minimize potential sources of confounding bias and provide more robust results. Multivariable MR (MVMR) analysis was conducted to adjust for potential genetic pleiotropy. Results: The study employed three SNPs, namely rs71631868, rs9271374, and rs116843408, as genetic tools to evaluate the causal association of osteocalcin with dementia. The IVW analysis indicated that osteocalcin may have a potential protective effect against AD with an odds ratio (OR) of 0.790 (95 % CI: 0.688-0.906; P < 0.001). However, no significant relationship was observed between osteocalcin and other types of dementia. Furthermore, the MVMR analysis indicated that the impact of osteocalcin on AD remained consistent even after adjusting for age-related macular degeneration and Type 2 diabetes with an OR of 0.856 (95 % CI: 0.744-0.985; P = 0.030). Conclusions: Our findings provide important insights into the role of osteocalcin in the pathogenesis of AD. Future research is required to clarify the underlying mechanisms and their clinical applications.

Postural deformities in Parkinson's disease: A bibliometric analysis based on web of science.

Objective: Postural deformities are common debilitating conditions during the progression of Parkinson's disease (PD). However, the underlying pathophysiology and optimal treatment strategy are unclear. In this study, we aimed to identify primary research fields, important achievements and emerging trends in postural deformities in PD. Methods: Web of Science Core Collection database was searched to retrieve all literature related to postural deformities in PD over the past 20 years. Data such as annual numbers of publications, countries of origin, publication journals, cooperation between countries, citation index and keywords were retrieved from the selected publications. Bibliometrix Package in R software were used for bibliometric analysis and visualization. Results: In total, 211 publications that met the criteria were collected. Analyses had shown that the annual numbers of publications increased gradually with fluctuations. Japan was the most prolific country (n = 59). Italy participated in international cooperation the most frequently. Parkinsonism & related disorders (n = 25) took a prominent lead among all journals, and the most productive institution in this area was University of Verona (n = 27). The most local cited author was Tinazzi Michele. According to the thematic map, "scoliosis", "fusion", and "balance" have rapidly become research hot spots in related fields. Conclusions: Articles pertaining to postural deformities in PD are still being published, in which the etiology is a combination of peripheral plus central involvement. Treatment approaches include rehabilitative exercises, oral medication, botulinum toxin injection, deep brain stimulation and spine surgery, which is getting current attention and would be a hot topic of future research.

Ion channel blockers and spinal cord injury.

The activation of a delayed secondary cascade of unsatisfactory cellular and molecular responses after a primary mechanical insult to the spinal cord causes the progressive degeneration of this structure. Disturbance of ionic homeostasis is part of the secondary injury process and plays an integral role in the early stage of spinal cord injury (SCI). The secondary pathology of SCI is complex and involves disturbance of the homeostasis of K(+) , Na(+) , and Ca(2+) . The effect of ion channel blockers on chronic SCI has also been proved. In this Mini-Review, we provide a comprehensive summary of the effects of ion channel blockers on the natural responses after SCI. Combination therapy is based on the roles of ions and disturbance of their homeostasis in SCI. The effects of ion channel blockers suggest that they have potential in the treatment of SCI, although the complexity of their effects shows that further knowledge is needed before they can be applied clinically.

Exploration of Immune-Related Gene Expression in Osteosarcoma and Association With Outcomes.

Importance: Host immune dysregulation is associated with initiation and development of osteosarcoma. In addition, immunotherapy for osteosarcomas requires some knowledge of the immune state of patients. Objective: To perform an immunogenomic landscape analysis based on The Cancer Genome Atlas (TCGA) project, which provides osteosarcoma samples with clinical information. Design, Setting, and Participants: This genetic association study was conducted from July 20, 2020, to September 20, 2020, as a secondary analysis of public data. Cox regression and risk score analyses were used to construct signatures of immune-related genes (IRGs) in 84 patients with osteosarcoma from TCGA with corresponding clinical information. Patients were divided into high- and low-risk groups with 42 individuals in each group according to their risk scores. Data were analyzed from July 20 to September 20, 2020. Main Outcomes and Measures: Differentially expressed genes (DEGs) were analyzed between groups, and potential molecular mechanisms, expression regulation, and immune cell infiltration were also explored using bioinformation methods. A prognostic model based on independent risk factors selected from multivariate Cox hazard ratio regression was established to estimate 1-year overall survival. Results: In this genetic association study based on 84 samples from patients with osteosarcoma from TCGA (mean [SD] age, 15.0 [4.8] years; 47 [56.0%] men; mean [SD] follow-up time, 4.1 [2.8] years), a total of 14 survival-associated IRGs were identified. Patients assigned to the high-risk group had worse survival than patients from the low-risk group (1 death [2.4%] vs 26 deaths [61.9%%]; P < .001). The protein digestion and absorption pathway was one of the associated pathways in the functional enrichment analysis (gene ratio, 2:8; P < .001). The prognostic model based on metastases at diagnosis and risk score performed well in 1-year overall survival estimations (area under the curve, 0.947; 95% CI, 0.832-0.972). The risk score was correlated with immune cell infiltration (B cells: r = 0.331; P = .002; macrophages: r = 0.410; P < .001; CD8 T cells: r = 0.230; P = .04). Conclusions and Relevance: This genetic association study developed a prognostic modeling tool for osteosarcoma based on IRG expression profiles, which could result in improved survival rates through more individualized therapies. Further research on IRG expression profiles could provide potential targets for future studies on immune treatment for osteosarcoma.

Mechanism of lung adenocarcinoma spine metastasis induced by CXCL17.

PURPOSE: Spine metastases are common in patients with lung adenocarcinoma (LUAD). Improving the clinical outcome of spine metastasis LUAD patients requires knowledge on the mechanism underlying the metastatic process. Here, we sought to decipher the effect and mechanism of C-X-C motif chemokine ligand 17 (CXCL17) on LUAD spine metastasis. METHODS: Clinical tumor tissue samples, lung cancer cell lines and a TCGA dataset were used for CXCL17 expression analyses. A transwell invasion assay was used to assess the chemotaxis capacity of mononuclear macrophages induced by CXCL17. Western blotting was performed to explore the mechanism of mononuclear macrophage chemotaxis towards CXCL17. A cell counting kit-8 assay was employed to investigate the effect of conditioned medium from M1 and M2 macrophages on the proliferation of lung cancer cells. RESULTS: We found that the expression of CXCL17 was higher in clinical LUAD samples and LUAD cell lines than in lung squamous cell carcinoma (LUSC) samples and cell lines. Moreover, we found that CXCL17 increased the migration of THP-1 mononuclear macrophages by activating the Src/FAK pathway. In addition, we found that conditioned medium from M2 macrophages promoted the proliferation of LUAD cells. CONCLUSIONS: From our data we conclude that CXCL17 is a key regulator of LUAD spine metastasis. CXCL17 and its downstream Src/FAK pathway may serve as clinical intervention targets.

A Network Pharmacology-Based Study on the Anti-Lung Cancer Effect of Dipsaci Radix.

OBJECTIVE: Dipsaci Radix (DR) has been used to treat fracture and osteoporosis. Recent reports have shown that myeloid cells from bone marrow can promote the proliferation of lung cancer. However, the action and mechanism of DR has not been well defined in lung cancer. The aim of the present study was to define molecular mechanisms of DR as a potential therapeutic approach to treat lung cancer. METHODS: Active compounds of DR with oral bioavailability ≥30% and drug-likeness index ≥0.18 were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform. The potential target genes of the active compounds and bone were identified by PharmMapper and GeneCards, respectively. The compound-target network and protein-protein interaction network were built by Cytoscape software and Search Tool for the Retrieval of Interacting Genes webserver, respectively. GO analysis and pathway enrichment analysis were performed using R software. RESULTS: Our study demonstrated that DR had 6 active compounds, including gentisin, sitosterol, Sylvestroside III, 3,5-Di-O-caffeoylquinic acid, cauloside A, and japonine. There were 254 target genes related to these active compounds as well as to bone. SRC, AKT1, and GRB2 were the top 3 hub genes. Metabolisms and signaling pathways associated with these hub genes were significantly enriched. CONCLUSIONS: This study indicated that DR could exhibit the anti-lung cancer effect by affecting multiple targets and multiple pathways. It reflects the traditional Chinese medicine characterized by multicomponents and multitargets. DR could be considered as a candidate for clinical anticancer therapy by regulating bone physiological functions.

Osteocalcin improves outcome after acute ischemic stroke.

BACKGROUND: Osteocalcin is related to energy metabolism, memory and the acute stress response, suggesting a relationship between bone and the brain. The need to explore the effect of osteocalcin on acute ischemic stroke is therefore urgent. RESULTS: Patients with better outcomes had higher serum osteocalcin levels than those whose NIHSS scores did not improve. Multivariable logistic regression analysis showed acceptable performance (area under the curve = 0.766). The effect of osteocalcin on the promotion of neuron survival was confirmed by Cell Counting Kit-8 experiments. In addition, osteocalcin could decrease proline hydroxylase 1 and inhibit the degradation of gasdermin D. CONCLUSIONS: We propose that osteocalcin can improve outcome after acute ischemic stroke in the acute period. By downregulating proline hydroxylase 1, osteocalcin leads glucose metabolism to the pentose phosphate pathway and therefore promotes neuronal survival through inhibiting pyroptosis. METHODS: Demographic data and laboratory results were obtained from patients with ischemic stroke in the acute period for analysis. A receiver operating characteristic curve was used to assess the discrimination of the prediction model. The potential effect of osteocalcin on cerebral ischemia and osteocalcin mechanism were explored in cultured primary rat cerebral cortical neurons treated with oxygen-glucose deprivation and reoxygenation.

The role of thrombospondin-1 and transforming growth factor-beta after spinal cord injury in the rat.

Spinal cord injury (SCI) continues to result in high morbidity and mortality throughout the world. An effective neuroprotective agent is still not available to counteract secondary damage caused by traumatic injury. Thrombospondin-1 (TSP-1) and transforming growth factor-beta (TGF-beta) have a role in angiogenesis, scar deposition, inflammation and may affect astrocyte phenotype and mobility. We investigated the role of TSP-1 and TGF-beta in a model of spinal cord injury in rats. Forty female Sprague-Dawley rats were randomly divided into two equal groups: the experimental group was subject to SCI using an impactor and the sham-operated group was not subject to SCI. These animals were sacrificed at 12 h and 24 h after SCI for immunochemistry and Western blot analysis of the injured spinal segment for the expression of the TSP-1 and TGF-beta proteins. We found that TSP-1 and TGF-beta expression increased immediately after SCI in the injured segment. After 12 h, TSP-1 concentrations increased more rapidly and dramatically than TGF-beta in the injured segment of the spinal cord. Elevations in TSP-1 and TGF-beta concentrations persisted for 24 h after injury. These results show that elevated expression of TSP-1 and TGF-beta can be detected in the injured segment of the spinal cord 12 and 24 h after injury. Thus, TSP-1 and TGF-beta may have a role in SCI.

CX3CL1 promotes lung cancer cell migration and invasion via the Src/focal adhesion kinase signaling pathway.

The present study investigated the role of C­X3­C motif chemokine ligand 1 (CX3CL1) in lung cancer cell migration and invasion and its potential mechanism. The expression levels of C­X3­C motif chemokine receptor 1 (CX3CR1) in six human lung cancer cell lines and one human bronchial epithelial cell line were assessed using reverse transcription­quantitative polymerase chain reaction and western blotting. Cell proliferation was assessed using the Cell Counting Kit­8 assay. Cell migration and invasion were examined using the Transwell assay, with and without Matrigel, respectively. The signaling pathway activated by CX3CL1 was analyzed via western blotting and inhibitory migration and invasion assays. CX3CR1 was expressed in the six lung cancer cell lines and one normal lung cell line. The lung cancer cell line, H460, was selected for further study. CX3CL1 did not significantly affect H460 proliferation; however, CX3CL1 did significantly enhance the migration and invasion of H460 cells. The Src/focal adhesion kinase (FAK) signaling pathway was activated in a time­dependent manner upon stimulation of CX3CL1. However, blocking Src activity with saracatinib prevented CX3CL1­mediated cell migration and invasion. Therefore, the findings indicated that CX3CL1 promotes lung cancer cell migration and invasion in vitro, and the Src/FAK signaling pathway serves a vital role in this process.

Lung cancer with bone metastases in the United States: an analysis from the Surveillance, Epidemiologic, and End Results database.

The present study used the Surveillance, Epidemiology and End Results (SEER) database to identify demographic and prognostic characteristics of lung cancer with bone metastases in the United States from 2010 to 2014. 30,364 patients with metastatic lung cancer to bones were identified in the SEER database. Their information on the basic characteristics and the histological signatures of the cancer was extracted and analyzed. Joinpoint analysis was used to test the trends in annual percentage change (APC) of the incidence. 1-year survival rate among patients with metastatic lung cancer to bones was only 20.2%, and median survival time was about 3.0 months for those patients. Young age, female sex, race other than white and black, tumor in lobes, smaller tumor, adenocarcinoma, and surgery for primary site were associated with a significant survival benefit. APC of the incidence almost increased steadily on the whole and reached the level of statistical significance among the patients older than age 60. Although there are some signatures associated with better prognosis, the overall outcome remains very poor in patients with metastatic lung cancer to bones. In addition, the incidence of lung cancer with bone metastases is increasing in certain subgroups in the United States.

Gene expression profile analysis of the progression of carotid atherosclerotic plaques.

The present study aimed to examine the universal gene expression signature and the underlying molecular mechanisms involved in the progression of carotid atherosclerotic plaques. The gene expression dataset, GSE28829, containing 13 early and 16 advanced carotid atherosclerotic plaques was selected for analysis. The differentially expressed genes (DEGs) were identified and analyzed using bioinformatics analyses, including cluster analysis, Gene Ontology (GO) and pathway enrichment analyses. Finally, a protein­protein interaction (PPI) was constructed and analyzed. A total of 515 downregulated and 243 downregulated DEGs were identified. The cluster analysis revealed two separate two groups. In addition, the GO terms enriched by the upregulated DEGs were associated with immune response, and the downregulated DEGs were associated with cell adhesion. The upregulated DEGs were enriched in pathways associated with signaling in the immune system, and the downregulated DEGs were enriched in pathways associated with muscle contraction. In the PPI network analysis, ITGAM and ACTN2 had the highest decrees of connectivity in the upregulated and downregulated DEGs, respectively. These findings suggested that deregulation of the immune system and smooth muscle cell cytoskeleton accelerates the progression of carotid atherosclerotic plaques. The DEGs identified may offer potential in the prevention and treatment of atherosclerosis in the carotid artery.

Gene expression profile analysis of the bone microenvironment in patients with spinal metastases.

The present study aimed to identify the underlying molecular mechanisms associated with spinal metastases. Gene expression profiles in cancellous bone samples from the spines of five patients with spinal metastases, with different primary cancers, and three normal control patients were measured using microarray analysis and subsequently compared. The differentially expressed genes (DEGs) identified were filtered using bioinformatics analyses followed by cluster analysis, gene ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Finally, a protein-protein interaction network was constructed and analyzed. A total of 152 upregulated and 388 downregulated DEGs were identified. The cluster analysis demonstrated a marked difference between the gene expression profiles of samples from patients with spinal metastases and those from normal patients. The GO terms enriched in the upregulated DEGs were associated with cell death, and those enriched in the downregulated DEGs were associated with the cell cycle. The upregulated DEGs were enriched in signaling pathways associated with tight junctions, and the downregulated DEGs were enriched in signaling pathways associated with porphyrin metabolism. In the PPI network constructed, transcription factor AP-1 and proliferating cell nuclear antigen had the highest connectivity degrees with the upregulated and downregulated DEGs, respectively. The gene expression profile data from the present study provides new insights into the underlying molecular mechanisms of spinal metastases, and will aid in the development of novel anticancer treatments.