Empathy in undergraduate medical students: a multi-center cross-sectional study in China.

BACKGROUND: Fostering empathy has been continuously emphasized in the global medical education. Empathy is crucial to enhance patient-physician relationships, and is associated with medical students' academic and clinical performance. However, empathy level of medical students in China and related influencing factors are not clear. METHODS: This was a cross-sectional study among medical students in 11 universities. We used the Jefferson Scale of Empathy Student-version of Chinese version to measure empathy level of medical students. Factors associated with empathy were identified by the univariate and multivariate logistic regression analyses. Based on the variables identified above, the nomogram was established to predict high empathy probability of medical students. Receiver operating characteristic curve, calibration plot and decision curve analysis were used to evaluate the discrimination, calibration and educational utility of the model. RESULTS: We received 10,901 samples, but a total of 10,576 samples could be used for further analysis (effective response rate of 97.02%). The mean empathy score of undergraduate medical students was 67.38 (standard deviation = 9.39). Six variables including gender, university category, only child or not, self-perception doctor-patient relationship in hospitals, interest of medicine, Kolb learning style showed statistical significance with empathy of medical students (P < 0.05). Then, the nomogram was established based on six variables. The validation suggested the nomogram model was well calibrated and had good utility in education, as well as area under the curve of model prediction was 0.65. CONCLUSIONS: We identify factors influencing empathy of undergraduate medical students. Moreover, increasing manifest and hidden curriculums on cultivating empathy of medical students may be needed among medical universities or schools in China.

Effect of tobacco usage on surgical site wound problems after primary total hip and total knee arthroplasty: A meta-analysis.

The meta-analysis aims to assess and compare the effect of tobacco usage on surgical site wound problems (SSWPs) after primary total hip and total knee arthroplasty (PTH&TKA). Using dichotomous random- or fixed-effects models, the outcomes of this meta-analysis were examined, and the odds ratio (OR) with 95% confidence intervals (CIs) was computed. Fifteen studies from 2001 to 2023 were enrolled for the present meta-analysis including 560 819 personals with PTH&TKA. Smokers had significantly higher SSWPs (OR, 1.53; 95% CI, 1.21-1.94, p < 0.001) compared with non-smokers in personals with PTH&TKA. Current smokers had significantly higher SSWPs (OR, 1.59; 95% CI, 1.40-1.80, p < 0.001) compared with non-smokers in personals with PTH&TKA. Current smokers had significantly higher SSWPs (OR, 1.42; 95% CI, 1.19-1.70, p < 0.001) compared with former smokers in personals with PTH&TKA. However, former smokers and non-smokers had no significant difference in SSWPs (OR, 1.11; 95% CI, 0.95-1.30, p = 19) in personals with PTH&TKA. The examined data revealed that in personals with PTH&TKA smokers had significantly higher SSWPs compared with non-smokers, and current smokers had significantly higher SSWPs compared with non-smokers and former smokers; however, former smokers and non-smokers had no significant difference in SSWPs. Yet, attention should be implemented while relating to its values since some of the comparisons were made using a low number of selected studies.

A multi-center cross-sectional study on identification of influencing factors of medical students' emotional engagement in China.

BACKGROUND: Studies exploring influencing factors of emotional engagement among medical students are scarce. Thus, we aimed to identify influencing factors of medical students' emotional engagement. METHODS: We carried out a multi-center cross-sectional study among 10,901 medical students from 11 universities in China. The Chinese version of Utrecht Work Engagement Scale-Student version (UWES-S) was used to evaluate emotional engagement level of medical students. The predictors related to engagement level were determined by the logistic regression analysis. Furthermore, we constructed a nomogram to predict emotional engagement level of medical students. RESULTS: A total of 10,576 sample were included in this study. The mean emotional engagement score was 74.61(± 16.21). In the multivariate logistic regression model, we found that males showed higher engagement level compared with females [odds ratio (OR) (95% confidence interval (CI)): 1.263 (1.147, 1.392), P < 0.001]. Medical students from the second batches of medical universities had higher engagement level and from "Project 985" universities had lower engagement level compared with 211 project universities [OR (95%CI): 1.376 (1.093, 1.733), P = 0.007; OR (95%CI): 0.682 (0.535, 0.868), P = 0.002]. Medical students in grade 4 and grade 2 presented lower engagement level compared with in grade 1 [OR (95%CI): 0.860 (0.752, 0.983), P = 0.027; OR (95%CI): 0.861 (0.757, 0.980), P = 0.023]. Medical students lived in provincial capital cities had higher engagement level compared with in country [OR (95%CI): 1.176 (1.022, 1.354), P = 0.024]. Compared with eight-year emotional duration, medical students in other emotional duration (three-year and four-year) had lower engagement level [OR (95%CI): 0.762 (0.628, 0.924), P = 0.006]. Medical students' engagement level increased with increases of grade point average and interest in studying medicine. Medical students learned by converging style showed lower engagement level [OR (95%CI): 0.827 (0.722, 0.946), P = 0.006] compared with accommodating style. The model showed good discriminative ability (area under curve = 0.778), calibrating ability and clinical utility. CONCLUSIONS: We identified influencing factors of medical students' emotional engagement and developed a nomogram to predict medical students' emotional engagement level, providing reference and convenience for educators to assess and improve emotional engagement level of medical students. It is crucial for educators to pay more attention to emotional engagement of medical students and adopt effective strategies to improve their engagement level.

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.

Identification of Bone Metastatic and Prognostic Alternative Splicing Signatures in Prostate Adenocarcinoma.

As the most common nonepithelial malignancy, prostate adenocarcinoma (PRAD) is the fifth chief cause of cancer mortality in men. Distant metastasis often occurs in advanced PRAD and most patients are dying from it. However, the mechanism of PRAD progression and metastasis is still unclear. It's widely reported that more than 94% of genes are selectively splicing in humans and many isoforms are particularly related with cancer progression and metastasis. Spliceosome mutations occur in a mutually exclusive manner in breast cancer, and different components of spliceosomes are targets of somatic mutations in different types of breast cancer. Existing evidence strongly supports the key role of alternative splicing in breast cancer biology, and innovative tools are being developed to use splicing events for diagnostic and therapeutic purposes. In order to identify if the PRAD metastasis is associated with alternative splicing events (ASEs), the RNA sequencing data and ASEs data of 500 PRAD patients were retrieved from The Cancer Genome Atlas (TCGA) and TCGASpliceSeq databases. By Lasso regression, five genes were screened to construct the prediction model, with a good reliability by ROC curve. Additionally, results in both univariate and multivariate Cox regression analysis confirmed the well prognosis efficacy of the prediction model (both P < 0.001). Moreover, a potential splicing regulatory network was established and after multiple-database validation, we supposed that the signaling axis of HSPB1 up-regulating the PIP5K1C - 46,721 - AT (P < 0.001) might mediate the tumorigenesis, progression and metastasis of PRAD via the key members of Alzheimer's disease pathway (SRC, EGFR, MAPT, APP and PRKCA) (P < 0.001).

Risk factors for postoperative surgical site wound problems after metastatic and primary spine tumour surgery: A meta-analysis.

A meta-analysis study was conducted to assess the risk factors (RFs) for postoperative surgical site wound problems (POSSWPs) after metastatic and primary spine tumour surgery (STS). A comprehensive literature examination until February 2023 was implemented, and 1786 linked studies were appraised. The 18 picked studies contained 18 580 subjects with surgery in the studies' baseline with and without different RFs. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to calculate the consequence of RFs for POSSWPs after metastatic and primary STS using the dichotomous and continuous styles and a fixed or random model. Subjects with surgical instrumentation in their surgery had a significantly higher rate of POSSWPs in STS (OR, 2.28; 95% CI, 1.49-3.49, P < 0.001) compared with those without surgical instrumentation. Subjects with preoperative chemotherapy had a significantly higher rate of POSSWPs in STS (OR, 1.81; 95% CI, 1.09-3.00, P = 0.02) compared with those without preoperative chemotherapy. Subjects with preoperative radiotherapy had a significantly higher rate of POSSWPs in STS (OR, 1.93; 95% CI, 1.12-3.34, P = 0.02) compared with those without preoperative radiotherapy. Subjects with corticosteroid intake had a significantly higher rate of POSSWPs in STS (OR, 2.89; 95% CI, 1.73-4.82, P < 0.001) compared with those without corticosteroid intake. No significant difference was found between males and females in the rate of POSSWPs in STS (OR, 0.95; 95% CI, 0.66-1.37, P = 0.78). Surgical instrumentation, preoperative chemotherapy, preoperative radiotherapy and corticosteroid are RFs for the higher rate of POSSWPs in STS; however, gender was not shown to be a risk factor. Though precautions should be taken when commerce with the consequences since some of the studies picked for this meta-analysis had low sample sizes.

Bibliometric analysis and mini-review of global research on pyroptosis in the field of cancer.

Pyroptosis is one of the mechanisms of programmed cell death (PCD) activated by inflammasomes and involved by the caspase family and the gasdermin family. During the oncogenesis and progression of tumors, pyroptosis is crucial, and complex withal. Currently, pyroptosis is the focus topic in the research field of oncology, but there is no single bibliometric analysis systematically studying 'pyroptosis and cancer'. Our study aimed to visualize the research status of pyroptosis in oncology and excavate the hotspots and prospects in this field. Furthermore, in consideration of the professional direction of researchers, we particularly emphasized articles on pyroptosis in gynecology and formed a mini systematic review. This bibliometric work integrated and analyzed all articles from ISI Web of Science: Science Citation Index Expanded (SCI-Expanded) (dated April 25th, 2022), based on quantitative and visual mapping approaches. Systematically reviewing articles on pyroptosis in gynecology helped us complement our analysis of research advancements in this field. Including 634 articles, our study found that the number of articles on pyroptosis in cancer increased exponentially in recent years. These publications came from 45 countries and regions headed by China and the US mainly aiming at the mechanism of pyroptosis in cell biology and biochemistry molecular biology, as well as the role of pyroptosis in the development and therapeutic application of various cancers. The top 20 most cited studies on this topic mostly came from the US, followed by China and England, and half of the articles cited more than 100 times in total were published in Nature. Moreover, as for gynecologic cancer, in vitro and bioinformatics analysis were the main methodology conducting to explore roles of pyroptosis-related genes (PRGs) and formation of inflammasomes in cancer progression and prognosis. Pyroptosis has evolved into a burgeoning research field in oncology. The cellular and molecular pathway mechanism of pyroptosis, as well as the effect of pyroptosis in oncogenesis, progression, and treatment have been the hot topic of the current study and provided us the future direction as the potential opportunities and challenges. We advocate more active cooperation to improve therapeutic strategies for cancer.

Sequencing technology as a major impetus in the advancement of studies into rheumatism: A bibliometric study.

Background: Rheumatism covers a wide range of diseases with complex clinical manifestations and places a tremendous burden on humans. For many years, our understanding of rheumatism was seriously hindered by technology constraints. However, the increasing application and rapid advancement of sequencing technology in the past decades have enabled us to study rheumatism with greater accuracy and in more depth. Sequencing technology has made huge contributions to the field and is now an indispensable component and powerful tool in the study of rheumatism. Methods: Articles on sequencing and rheumatism, published from 1 January 2000 to 25 April 2022, were retrieved from the Web of Science™ (Clarivate™, Philadelphia, PA, USA) database. Bibliometrix, the open-source tool, was used for the analysis of publication years, countries, authors, sources, citations, keywords, and co-words. Results: The 1,374 articles retrieved came from 62 countries and 350 institutions, with a general increase in article numbers during the last 22 years. The leading countries in terms of publication numbers and active cooperation with other countries were the USA and China. The most prolific authors and most popular documents were identified to establish the historiography of the field. Popular and emerging research topics were assessed by keywords and co-occurrence analysis. Immunological and pathological process in rheumatism, classification, risks and susceptibility, and biomarkers for diagnosis were among the hottest themes for research. Conclusions: Sequencing technology has been widely applied in the study of rheumatism and propells research in the area of discovering novel biomarkers, related gene patterns and physiopathology. We suggest that further efforts be made to advance the study of genetic patterns related to rheumatic susceptibility, pathogenesis, classification and disease activity, and novel biomarkers.

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

WE aimed to reveal the correlation between ovarian cancer (OV) metastasis and cancer stemness in OV. RNA-seq data and clinical information of 591 OV samples (551 without metastasis and 40 with metastasis) were obtained from TCGA. The edgeR method was used to determine differentially expressed genes (DEGs) and transcription factors (DETFs). Then, mRNA expression-based stemness index was calculated using one-class logistic regression (OCLR). Weighted gene co-expression network analysis (WGCNA) was used to define stemness-related genes (SRGs). Univariate and multivariate Cox proportional hazard regression were conducted to identify the prognostic SRGs (PSRGs). PSRGs, DETFs, and 50 hallmark pathways quantified by gene set variation analysis (GSVA) were integrated into Pearson co-expression analysis. Significant co-expression interactions were utilized to construct an OV metastasis-specific regulation network. Cell communication analysis was carried out based on single cell RNA sequencing data to explore the molecular regulation mechanism of OV. Eventually, assay for targeting accessible-chromatin with high throughout sequencing (ATAC), chromatin immunoprecipitation sequencing (ChIP-seq) validation, and multiple data sets were used to validate the expression levels and prognostic values of key stemness-related signatures. Moreover, connectivity map (CMap) was used to identify potential inhibitors of stemness-related signatures. Based on edgeR, WGCNA, and Cox proportional hazard regression, 22 PSRGs were defined to construct a prognostic prediction model for metastatic OV. In the metastasis-specific regulation network, key TF-PSRS interaction pair was NR4A1-EGR3 (correlation coefficient = 0.81, p < 0.05, positive), and key PSRG-hallmark pathway interaction pair was EGR3-TNFα signaling via NFκB (correlation coefficient = 0.44, p < 0.05, positive), which were validated in multi-omics databases. Thioridazine was postulated to be the most significant compound in treatment of OV metastasis. PSRGs played critical roles in OV metastasis. Specifically, EGR3 was the most significant PSRG, which was positively regulated by DETF NR4A1, inducing metastasis via TNFα signaling.

WTAP contributes to the tumorigenesis of osteosarcoma via modulating ALB in an m6A-dependent manner.

PURPOSE: Osteosarcoma (OS) is a prevalent bone malignancy mainly occurred in adolescents. WTAP/N6-methyladenosine (m6A) modification is confirmed to be involved in OS progression. This study is conducted to bring some novel insights to the action mechanism of WTAP/m6A under the hidden pathogenesis of OS. METHODS: qRT-PCR was executed to evaluate the expression levels of WTAP and ALB. ALB protein level in OS cells was measured by western blotting. The content of m6A in total RNA was assessed by m6A quantification assay. Me-RIP, dual luciferase reporter, and mRNA stability assays confirmed the target relationship of WTAP with ALB. With the use of the wound healing, CCK-8, and transwell invasion assays, the functional relationship between WTAP and ALB in OS cells was confirmed. The influences of WTAP on tumor growth in vivo were performed in the xenograft model of mouse. RESULTS: WTAP was increased but ALB was diminished in OS tissues and/or cell lines. WTAP modulated ALB expression in an m6A-dependent manner. Silencing of WTAP retarded the development of OS via inhibiting cell viability, migration, invasion, and tumor growth. Knockdown of ALB exerted the opposite effects on OS progression. Additionally, ALB deficiency partially eliminated the inhibiting effects of WTAP silencing on cellular processes in OS. CONCLUSIONS: This is the first report to clarify the interaction of WTAP/m6A with ALB in OS progression. These experimental data to some extent broadened the horizons of WTAP/m6A in the development of OS.

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.

A bibliometric analysis of the role of microbiota in trauma.

Introduction: Over the last several decades, the gut microbiota has been implicated in the formation and stabilization of health, as well as the development of disease. With basic and clinical experiments, scholars are gradually understanding the important role of gut microbiota in trauma, which may offer novel ideas of treatment for trauma patients. In this study, we purposed to summarize the current state and access future trends in gut microbiota and trauma research. Methods: We retrieved relevant documents and their published information from the Web of Science Core Collection (WoSCC). Bibliometrix package was responsible for the visualized analysis. Results: Totally, 625 documents were collected and the number of annual publications kept increasing, especially from 2016. China published the most documents while the USA had the highest local citations. The University of Colorado and Food & Function are respectively the top productive institution and journal, as PLOS One is the most local cited journal. With the maximum number of articles and local citations, Deitch EA is supported to be the most contributive author. Combining visualized analysis of keywords and documents and literature reading, we recognized two key topics: bacteria translocation in trauma and gut microbiota's effect on inflammation in injury, especially in nervous system injury. Discussion: The impact of gut microbiota on molecular and pathological mechanism of inflammation is the focus now. In addition, the experiments of novel therapies based on gut microbiota's impact on trauma are being carried out. We hope that this study can offer a birds-eye view of this field and promote the gradual improvement of it.

The Recurrent-Specific Regulation Network of Prognostic Stemness-Related Signatures in Low-Grade Glioma.

Gliomas including astrocytomas, oligodendrogliomas, mixed oligoastrocytic, and mixed glioneuronal tumors are an important group of brain tumors. Based on the 2016 WHO classification for tumors in the central nervous system, gliomas were classified into four grades, from I to IV, and brain lower grade glioma (LGG) consists of grade II and grade III. Patients with LGG may undergo recurrence, which makes clinical treatment tough. Stem cell-like features of cancer cells play a key role in tumor's biological behaviors, including tumorigenesis, development, and clinical prognosis. In this article, we quantified the stemness feature of cancer cells using the mRNA stemness index (mRNAsi) and identified stemness-related key genes based on correlation with mRNAsi. Besides, hallmark gene sets and translate factors (TFs) which were highly related to stemness-related key genes were identified. Therefore, a recurrency-specific network was constructed and a potential regulation pathway was identified. Several online databases, assay for transposase-accessible chromatin using sequencing (ATAC-seq), single-cell sequencing analysis, and immunohistochemistry were utilized to validate the scientific hypothesis. Finally, we proposed that aurora kinase A (AURKA), positively regulated by Non-SMC Condensin I Complex Subunit G (NCAPG), promoted E2F target pathway in LGG, which played an important role in LGG recurrence.

WTAP contributes to the tumorigenesis of osteosarcoma via modulating ALB in an m6A-dependent manner.

PURPOSE: Osteosarcoma (OS) is a prevalent bone malignancy mainly occurred in adolescents. WTAP/N6-methyladenosine (m6A) modification is confirmed to be involved in OS progression. This study is conducted to bring some novel insights to the action mechanism of WTAP/m6A under the hidden pathogenesis of OS. METHODS: qRT-PCR was executed to evaluate the expression levels of WTAP and ALB. ALB protein level in OS cells was measured by western blotting. The content of m6A in total RNA was assessed by m6A quantification assay. Me-RIP and dual luciferase reporter assays confirmed the target relationship of WTAP with ALB. With the use of the wound healing, CCK-8, and transwell invasion assays, the functional relationship between WTAP and ALB in OS cells was confirmed. The influences of WTAP on tumor growth in vivo were performed in the xenograft model of mouse. RESULTS: WTAP was increased but ALB was diminished in OS tissues and/or cell lines. WTAP modulated ALB expression in an m6A-dependent manner. Silencing of WTAP retarded the development of OS via inhibiting cell viability, migration, invasion, and tumor growth. Knockdown of ALB exerted the opposite effects on OS progression. Additionally, ALB deficiency partially eliminated the inhibiting effects of WTAP silencing on cellular processes in OS. CONCLUSIONS: This is the first report to clarify the interaction of WTAP/m6A with ALB in OS progression. These experimental data to some extent broadened the horizons of WTAP/m6A in the development of OS.

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.

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.

The role of tetraspanins pan-cancer.

Tetraspanins (TSPANs) are a class of four-transmembrane segmented proteins. The precise functions of TSPANs and their roles in pan-cancer are unclear. In this work, we analyzed TSPAN1, TSPAN10, TSPAN11, TSPAN12, TSPAN13, TSPAN14, TSPAN15, TSPAN16, TSPAN17, TSPAN18, TSPAN18-AS1, TSPAN19, TSPAN2, TSPAN3, TSPAN31, TSPAN32, TSPAN33, TSPAN4, TSPAN5, TSPAN6, TSPAN7, TSPAN8, TSPAN9, TSPAN9-IT1 (24 TSPAN family genes) in relation to tumor characteristics from 11,057 TCGA samples across 33 cancer types. On 24 TSPAN family genes, multidimensional studies were conducted, including gene differential expression, immunological subtype analysis, clinical analysis, stemness indices analysis, drug sensitivity analysis, alteration analysis, and multi-omics validation (including ATAC-seq validation, single-cell sequencing validation, and other external validation). Genes were differentially expressed in 33 cancers, and several of them showed high consistency in terms of tumor characteristics. In particular, the potential roles of TSPAN15 and TSPAN1 in cancer deserve further attention.

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.

The role of toll-like receptors (TLRs) in pan-cancer.

BACKGROUND: Toll-like receptors (TLRs) are important components of the innate and adaptive immune systems, and abnormal TLR expression has been linked to a variety of cancers. However, there was a lack of clarity on the association of TLR stimulation with the carcinogenesis of cancer. The study's goal was to analyse the clinical importance of TLRs expression at the mRNA level in pan-cancer datasets, as well as the link between TLR expression and carcinogenesis, progression, and clinical prognosis. METHODS: The expression profile of TLRs derived from UCSC pan-cancer data was analysed in multiple dimensions, including clinical analysis, immunological subtype analysis, tumour microenvironment (TME) analysis, tumour stem cell correlation analysis, and drug sensitivity analysis. Additionally, we analyse protein-protein interactions, functional enrichment, and chromatin accessibility, as well as TLR expression in single-cell sequencing data. RESULTS: Our multi-omics analysis results imply that TLRs may operate as a biological marker for carcinogenesis and progression, a potential target for anti-tumour therapy, and a prognostic biomarker, laying the theoretical groundwork for future translational medicine research. CONCLUSION: TLRs are involved in the formation of malignancies and can be explored in further detail as potential prognostic indicators. Key MessagesToll-like receptors (TLRs) are key factors in the process of the innate and adaptive immune response, and their aberrant expression of TLRs have been widely reported in various cancer. However, the association between TLRs stimulation and tumorigenesis of cancer has not been well clarified.In this study, in the pan-cancer data, integrated TLR family gene expression analysis, clinical correlation analysis, immune subtype correlation analysis, tumour microenvironment correlation analysis, tumour stem cell correlation analysis, and drug sensitivity correlation analysis were performed.TLRs play an important role in the development of tumours and can be studied in depth as potential prognostic markers.