Clinical Outcomes of Percutaneous Transforaminal Endoscopic Discectomy Assisted with Selective Nerve Root Block for Treating Radicular Pain with Diagnostic Uncertainty in the Elderly.

Purpose: To investigate the clinical outcomes of percutaneous transforaminal endoscopic discectomy assisted with selective nerve root block for treating radicular pain with diagnostic uncertainty in the elderly. Methods: A total number of 36 elderly patients were included in the study. Clinical outcomes collected for analysis include operative time, hospital stay time, Visual Analog Scale, and Oswestry Disability Index before and after the surgery, the global outcome based on the Macnab outcome criteria. Results: Seventeen males and nineteen females with a mean age of 73.72 ± 7.15 were included in this study. Radicular pain was the main complaint of all the patients with the least symptom duration of two months. Radiological findings showed that 80.6% of the patients with multilevel disc herniation, 16.7% received lumbar fusion surgery before, and 8.3% with degenerative scoliosis. Besides, 69.4% of the patients have at least one comorbidity. 85.4% of the patients showed a positive response to selective nerve root block, and 91.6% of the patients reported a favorable outcome at the last follow-up. The mean value of pre-operative leg pain was 7.56 ± 0.74 and dramatically decreased after surgery (2.47 ± 0.81, P < 0.001). Besides, the mean value of Oswestry Disability Index decreased from 43.03 ± 4.43 to 5.92 ± 5.24 (P < 0.001) one year after the surgery. Conclusion: Multilevel degeneration of the lumbar spine is common in elderly patients. Identifying the responsible segment and decompressing the nerve root through minimally invasive surgery can provide a satisfactory clinical outcome for those with radicular pain as their primary complaint. And selective nerve root block is a reliable diagnostic tool for those with an ambiguous diagnosis.

RBP7 Regulated by EBF1 Affects Th2 Cells and the Oocyte Meiosis Pathway in Bone Metastases of Bladder Urothelial Carcinoma.

BACKGROUND: Bladder urothelial carcinoma (BLCA) is a malignancy with a high incidence worldwide. One-third of patients may experience aggressive progression later on, and 70% of patients who have undergone surgical intervention will still suffer from metastasis. MATERIALS AND METHODS: RNA sequencing profiles of BLCA samples were obtained from The Cancer Genome Atlas (TCGA) database. Differential expression and univariate Cox regression analyses were performed to identify prognosis-related differentially expressed immune genes (DEIGs). Subsequently, a proportional hazards model of DEIGs was then constructed by univariate regression analysis. Differential expression and correlation analyses, CIBERSORT, Single Sample Gene Set Enrichment Analysis (ssGSEA), GSVA were conducted on transcription factors (TFs), immune cells/pathways and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The regulation network was then constructed. Eventually, ATAC-seq, ChIP-seq, scRNA-seq, and multiple online databases were employed for further validation. RESULTS: A proportional hazards model of 31 DEIGs was constructed and risk score was calculated and proven to be a independent prognostic factor. Then 5 immune genes were characterized to be significantly correlated with bone metastasis, stage and TF expression simultaneously. 4 TFs were identified to be significantly correlated with prognosis and RBP7 expression. 5 immune cells/pathways were revealed to be significantly correlated with RBP7 expression. Only 1 KEGG pathway was identified to be significant in Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) analyses. The regulatory relationship was then constructed, in which the correlation between EBF1 and RBP7 (R = 0.677, p < 0.001), Th2 cells and RBP7 (R = 0.23, p < 0.001), the oocyte meiosis pathway and RBP7 (R = 0.14, p = 0.042) were the most statistically significant. The results were further confirmed by Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq), Chromatin Immunoprecipitation sequencing (ChIP-seq), single-cell RNA sequencing (scRNA-seq), and multiple online databases validation. CONCLUSIONS: This study revealed that the EBF1-RBP7 regulatory relationship had potential importance in the bone metastasis in BLCA through Th2 cells and the oocyte meiosis pathway.

Global trends in research of fibroblasts associated with rheumatoid diseases in the 21st century: A bibliometric analysis.

Background: Rheumatoid Diseases (RDs) are a group of systemic auto-immune diseases that are characterized by chronic synovitis, and fibroblast-like synoviocytes (FLSs) play an important role in the occurrence and progression of synovitis. Our study is the first to adopt bibliometric analysis to identify the global scientific production and visualize its current distribution in the 21st century, providing insights for future research through the analysis of themes and keywords. Methods: We obtained scientific publications from the core collection of the Web of Science (WoS) database, and the bibliometric analysis and visualization were conducted by Biblioshiny software based on R-bibliometrix. Results: From 2000 to 2022, a total of 3,391 publications were reviewed. China is the most prolific country (n = 2601), and the USA is the most cited country (cited 7225 times). The Center of Experimental Rheumatology at University Hospital Zürich supported the maximum number of articles (n = 40). Steffen Gay published 85 records with 6263 total citations, perhaps making him the most impactful researcher. Arthritis and Rheumatism, Annals of Rheumatic Diseases, and Rheumatology are the top three journals. Conclusion: The current study revealed that rheumatoid disease (RD)-related fibroblast studies are growing. Based on the bibliometric analysis, we summarized three important topics: activation of different subsets of fibroblasts; regulation of fibroblast function; and in vitro validation of existing discoveries. They are all valuable directions, which provide reference and guidance for researchers and clinicians engaged in the research of RDs and fibroblasts.

Bibliometric analysis of research on gene expression in spinal cord injury.

Background: Spinal cord injury (SCI) is a severe disease with motor and sensory function being destroyed, which leads to a poor prognosis and a serious financial burden. It is urgent to figure out the molecular and pathological mechanisms of SCI to develop feasible therapeutic strategies. This article aims to review documents focused on gene expression in SCI and summarize research hotspots and the development process in this field. Methods: Publications of SCI-related studies from 2000 to 2022 were retrieved from the Web of Science Core Collection database. Biblioshiny was used to evaluate the research performance, core authors, journals and contributed countries, together with trend topics, hotspots in the field, and keyword co-occurrence analysis. Visualized images were obtained to help comprehension. Results: Among 351 documents, it was found that the number of annual publications increased in general. The most productive country was China, followed by the United States with the highest influence and the most international cooperation. Plos One was the journal of the maximum publications, while Journal of Neuroscience was the most influential one. According to keyword co-occurrence and trend topics analysis, these articles mainly focused on molecular and pathological mechanisms as well as novel therapies for SCI. Neuropathic pain, axonal regeneration and messenger RNA are significant and promising research areas. Conclusion: As the first bibliometric study focused on gene expression in SCI, we demonstrated the evolution of the field and provided future research directions like mechanisms and treatments of SCI with great innovativeness and clinical value. Further studies are recommended to develop more viable therapeutic methods for SCI.

Sagittal alignment of the cervical spine: radiographic analysis of 111 asymptomatic adolescents, a retrospective observational study.

PURPOSE: To describe the cervical spine morphology and explore its relationship to global sagittal alignment parameters in the asymptomatic adolescent population.  METHODS: A total of 111 adolescent subjects were included. Sagittal alignment parameters, including C7 Slope, C2-C7 Cobb, C2-7 plumb line (PL), C2-S1 Sagittal Vertical Axis (SVA), C7-S1 SVA, T5-12 Cobb, T10-L2 Cobb, L1-S1 Cobb, pelvic incidence (PI), pelvic tilt (PT) and sacral slope (SS), were obtained from lateral radiographs.  RESULTS: Forty-four males and sixty-seven females with a mean age of 16.12 ± 2.40 years were included in this study. The mean values of C7 Slope, C2-7 Cobb and C2-7PL were 20.45 ± 8.88°, -7.72 ± 12.10°, and 13.53 ± 11.63 mm, respectively. C2-7 Cobb, C7 Slope showed significant differences between the male and female groups. Correlation analysis showed that C7 slope was significantly correlated with C2-7 Cobb (r = -0.544, P < 0.001), C2-S1 SVA (r = 0.335, P < 0.001), and C7-S1 SVA (r = 0.310, P = 0.001), but not lumbosacral parameters(L5-S1 Cobb, PI, PT, SS). Using a modified method of Toyama to describe the cervical spine morphology, there were 37 cases (33.3%) in the Lordotic group, and C7 slope, C2-7 Cobb and C2-7PL showed significant differences between groups. According to C2-C7 Cobb, there were 80 Lordotic cases (72.1%). C7 slope and C2-7PL were significantly different between the two groups. CONCLUSION: The cervical spine morphology of asymptomatic adolescents varies widely, from lordotic to kyphotic. Combining different classification methods provides a better understanding of the morphology of the cervical spine. C7 slope is an important predictor of global sagittal balance and C2-7PL is a key parameter for restoring cervical lordosis, which should be considered pre-operatively and for conservative treatment. Cervical regional sagittal alignment parameters are not correlated with lumbosacral parameters, and C2-7 Cobb, C7 Slope showed significant differences between males and females.

Repression of enhancer RNA PHLDA1 promotes tumorigenesis and progression of Ewing sarcoma via decreasing infiltrating T-lymphocytes: A bioinformatic analysis.

Background: The molecular mechanisms of EWS-FLI-mediating target genes and downstream pathways may provide a new way in the targeted therapy of Ewing sarcoma. Meanwhile, enhancers transcript non-coding RNAs, known as enhancer RNAs (eRNAs), which may serve as potential diagnosis markers and therapeutic targets in Ewing sarcoma. Materials and methods: Differentially expressed genes (DEGs) were identified between 85 Ewing sarcoma samples downloaded from the Treehouse database and 3 normal bone samples downloaded from the Sequence Read Archive database. Included in DEGs, differentially expressed eRNAs (DEeRNAs) and target genes corresponding to DEeRNAs (DETGs), as well as the differentially expressed TFs, were annotated. Then, cell type identification by estimating relative subsets of known RNA transcripts (CIBERSORT) was used to infer portions of infiltrating immune cells in Ewing sarcoma and normal bone samples. To evaluate the prognostic value of DEeRNAs and immune function, cross validation, independent prognosis analysis, and Kaplan-Meier survival analysis were implemented using sarcoma samples from the Cancer Genome Atlas database. Next, hallmarks of cancer by gene set variation analysis (GSVA) and immune gene sets by single-sample gene set enrichment analysis (ssGSEA) were identified to be significantly associated with Ewing sarcoma. After screening by co-expression analysis, most significant DEeRNAs, DETGs and DETFs, immune cells, immune gene sets, and hallmarks of cancer were merged to construct a co-expression regulatory network to eventually identify the key DEeRNAs in tumorigenesis of Ewing sarcoma. Moreover, Connectivity Map Analysis was utilized to identify small molecules targeting Ewing sarcoma. External validation based on multidimensional online databases and scRNA-seq analysis were used to verify our key findings. Results: A six-different-dimension regulatory network was constructed based on 17 DEeRNAs, 29 DETFs, 9 DETGs, 5 immune cells, 24 immune gene sets, and 8 hallmarks of cancer. Four key DEeRNAs (CCR1, CD3D, PHLDA1, and RASD1) showed significant co-expression relationships in the network. Connectivity Map Analysis screened two candidate compounds, MS-275 and pyrvinium, that might target Ewing sarcoma. PHLDA1 (key DEeRNA) was extensively expressed in cancer stem cells of Ewing sarcoma, which might play a critical role in the tumorigenesis of Ewing sarcoma. Conclusion: PHLDA1 is a key regulator in the tumorigenesis and progression of Ewing sarcoma. PHLDA1 is directly repressed by EWS/FLI1 protein and low expression of FOSL2, resulting in the deregulation of FOX proteins and CC chemokine receptors. The decrease of infiltrating T-lymphocytes and TNFA signaling may promote tumorigenesis and progression of Ewing sarcoma.

Effects of physical and mental health factors and family function on the self-perception of aging in the elderly of Chinese community.

BACKGROUND: To examine the effects of physical and mental health factors and family functioning on the self-perception of ageing in elderly people. METHODS: A random cluster sampling method was used to select elderly people aged over 60 from three communities in Handan City. Subjects were evaluated via face-to-face interviews using the Chinese version of the Ageing Perception Questionnaire, the Family Function Scale, the SF-36 Short-Form Health Survey, and a self-compiled general questionnaire. A single factor and stepwise multiple regression analysis were evaluated using SPSS 17.0 software. RESULTS: Among the 1815 elderly people surveyed, the total negative dimension score was 91.67 ± 16.58 with an index of 73.34%, which is higher than the positive dimension score (6.01 ± 0.52, 60.10%). Elderly people with varying degrees of family dysfunction accounted for 11.63%, and the score for self-perceived ageing in elderly participants with good family function was 95.74 ± 12.63. The proportions with poor physical and mental health factors were 45.40% and 28.10%, respectively, and the scores for ageing self-perception in elderly participants with good or moderate mental health were 89.11 ± 12.65 and 86.22 ± 12.58, respectively. A stepwise multiple regression analysis showed that age, presence of a spouse, and family function were positive protective factors for ageing self-perception, while physical health factors were risk factors for the positive dimension of self-perceived ageing. Age and family function were risk factors for the negative dimension of ageing self-perception, while physical and mental health factors were protective factors for the negative dimension of self-perceived ageing. CONCLUSIONS: Younger elderly and elderly people with good family function have positive self-perceptions of ageing, while elderly participants with poor physical and mental health have a negative perception of ageing.

Construction of the prognostic enhancer RNA regulatory network in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is a common malignant tumor in osteoarticular system, the 5-year overall survival of which is poor. Enhancer RNAs (eRNAs) have been implicated in the tumorigenesis of various cancer types, whereas their roles in OS tumorigenesis remains largely unclear. METHODS: Differentially expressed eRNAs (DEEs), transcription factors (DETFs), target genes (DETGs) were identified using limma (Linear Models for Microarray Analysis) package. Prognosis-related DEEs were accessed by univariate Cox regression analysis. A multivariate model was constructed to evaluate the prognosis of OS samples. Prognosis-related DEEs, DETFs, DETGs, immune cells, and hallmark gene sets were co-analyzed to construct an regulatory network. Specific inhibitors were also filtered by connectivity Map analysis. External validation and scRNA-seq analysis were performed to verify our key findings. RESULTS: 3,981 DETGs, 468 DEEs, 51 DETFs, and 27 differentially expressed hallmark gene sets were identified. A total of Multivariate risk predicting model based on 18 prognosis-related DEEs showed a high accuracy (area under curve (AUC) = 0.896). GW-8510 was the candidate inhibitor targeting prognosis-related DEEs (mean = 0.670, p < 0.001). Based on the OS tumorigenesis-related regulation network, we identified that CCAAT enhancer binding protein alpha (CEBPA, DETF) may regulate CD8A molecule (CD8A, DEE), thereby promoting the transcription of CD3E molecule (CD3E, DETG), which may affect allograft rejection based on CD8+ T cells. CONCLUSION: We constructed an eRNA-based prognostic model for predicting the OS patients' prognosis and explored the potential regulation network for OS tumorigenesis by an integrated bioinformatics analysis, providing promising therapeutic targets for OS patients.

Construction of Bone Metastasis-Specific Regulation Network Based on Prognostic Stemness-Related Signatures in Prostate Cancer.

Background: We planned to uncover the cancer stemness-related genes (SRGs) in prostate cancer (PCa) and its underlying mechanism in PCa metastasis. Methods: We acquired the RNA-seq data of 406 patients with PCa from the TCGA database. Based on the mRNA stemness index (mRNAsi) calculated by one-class logistic regression (OCLR) algorithm, SRGs in PCa were extracted by WGCNA. Univariate and multivariate regression analyses were applied to uncover OS-associated SRGs. Gene Set Variation Analysis (GSVA), Gene Set Enrichment Analysis (GSEA), and Pearson's correlation analysis were performed to discover the possible mechanism of PCa metastasis. The significantly correlated transcription factors of OS-associated SRGs were also identified by Pearson's correlation analysis. ChIP-seq was applied to validate the binding relationship of TFs and OS-associated SRGs and spatial transcriptome and single-cell sequencing were performed to uncover the location of key biomarkers expression. Lastly, we explored the specific inhibitors for SRGs using CMap algorithm. Results: We identified 538 differentially expressed genes (DEGs) between non-metastatic and metastatic PCa. Furthermore, OS-associated SRGs were identified. The Pearson correlation analysis revealed that FOXM1 was significantly correlated with NEIL3 (correlation efficient =0.89, p < 0.001) and identified hallmark_E2F_targets as the potential pathway mechanism of NEIL3 promoting PCa metastasis (correlation efficient =0.58, p < 0.001). Single-cell sequencing results indicated that FOXM1 regulating NEIL3 may get involved in the antiandrogen resistance of PCa. Rottlerin was discovered to be a potential target drug for PCa. Conclusion: We constructed a regulatory network based on SRGs associated with PCa metastasis and explored possible mechanism.