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With the continuous advancement of materials science, cell biology, and biotechnology, tissue engineering has introduced novel solutions to traditional wound healing approaches, particularly demonstrating significant potential in addressing complex or non-healing wounds. One of the key technologies in this field, dermal scaffolds, serve as wound coverage materials that mimic the structural framework of the dermis. They primarily assume the function of extracellular matrix, providing space for cell attachment, migration, and proliferation, thus supporting cellular growth and regulating multiple biological processes in healing. Tissue engineering utilizes combinations of natural or synthetic scaffolds, seeded cells, or growth factors to induce distinct effects in angiogenesis, extracellular matrix deposition, and functional recovery. Therefore, various bioengineered dermal scaffolds hold significant potential for clinical translation in wound healing. This review outlines various extracellular matrix molecules utilized in the development of dermal scaffolds, emphasizes recent progress in cell- and growth factor-modified scaffolds, and discusses the challenges and future perspectives in this evolving field.

Abstract Background Intervertebral disc degeneration (IVDD) is a significant cause of global disability, reducing labor productivity, increasing the burden on public health, and affecting socio-economic well-being. Currently, there is a lack of recognized clinical approaches for molecular classification and precision therapy. Methods Chondrocyte differentiation and prognosis-related genes were extracted from single-cell RNA sequencing and multi-omics data in the Gene Expression Omnibus (GEO) database through chondrocyte trajectory analysis and non-parametric tests. Subsequently, a precise IVDD risk stratification system was developed using ConsensusClusterPlus analysis. The clinical significance of molecular typing was demonstrated through case–control trials involving IVDD patients. Specific inhibitors of molecular typing were predicted using the pRRophetic package in R language and then validated in vitro. Results A stratified model for IVDD, considering chondrocyte differentiation and demonstrating high clinical relevance, was developed using a set of 44 chondrocyte fate genes. Extensive analyses of multi-omics data confirmed the clinical relevance of this model, indicating that cases in the High Chondrocyte Scoring Classification (HCSC) group had the most favorable prognosis, whereas those in the Low Chondrocyte Scoring Classification (LCSC) group had the worst prognosis. Additionally, clinical case–control studies provided evidence of the utility of IVDD molecular typing in translational medicine. A gene expression-based molecular typing approach was used to create a matrix identifying potential inhibitors specific to each IVDD subtype. In vitro experiments revealed that gefitinib, a drug designed for LCSC, not only had protective effects on chondrocytes but also could induce the conversion of LCSC into the HCSC subgroup. Therefore, IVDD molecular typing played a critical role in assisting clinicians with risk stratification and enabling personalized treatment decisions. Conclusion The results of the study have provided a comprehensive and clinically relevant molecular typing for IVDD, involving a precise stratification system that offers a new opportunity for customizing personalized treatments for IVDD.

Abstract Background Empathy of medical students is crucial, yet it tends to decline as students enter later academic years. Empathy appeared to be affected by the learning environment (LE), which could be a potential contributor. We conducted a cross-sectional study to investigate the association between LE and empathy. Method The study comprised overall 10,901 medical students from 12 Chinese medical schools. Jefferson Scale of Empathy (JSE) was utilized to assess empathy, while a 5-point question and the Johns Hopkins Learning Environment Scale were employed to evaluate LE. JSE scores were compared across LE levels using Pearson Chi-square, Welch’s ANOVA, and univariable linear regression. After adjusting for covariates, multivariable linear and logistic regression were used to assess the independent connection between LE and empathy. Confounders were controlled by stratified subgroup analysis. Results LE was significantly associated with medical students’ empathy, as shown by the Pearson Chi-square test (p

Abstract Background Colon adenocarcinoma (COAD) ranks as the third most prevalent and lethal cancer in 2020, with metastasis being the primary cause of cancer-related mortality. A comprehensive understanding of the mechanism underlying distant metastasis is imperative for enhancing the prognosis and quality of life of patients with COAD. Methods This study employed gene set enrichment analysis (GSEA) on RNA-sequencing data from 408 patients with COAD in The Cancer Genome Atlas (TCGA) database. GSEA analysis was applied to find the significant hallmark gene set, and genes in the significant hallmark gene set was performed by univariate Cox regression to select the key gene. Then, multivariate Cox regression model was constructed. And various databases were utilized to validate and find the significant oncoprotein and hallmark gene set of the key gene. In addition, the expression of key regulators in para-carcinoma tissue, colon cancer and distant metastases samples were detected by real-time PCR, Immunohistochemistry and Western blot. Additionally, the biological functions were examined by in vitro and in vivo experiments. The scRNA-seq and CellphoneDB were performed to explore cell characters in COAD and the potential mechanism of metastasis. Results The regulatory network analysis revealed SRC/YAP1 as the most significant oncoprotein and signature gene set associated with SNTB1. Moreover, significant SNTB1 overexpression in COAD metastatic tissues was observed compared to para-carcinoma and primary COAD tissues. Co-immunoprecipitation assays demonstrated the formation of a complex between SNTB1 and SRC proteins. Furthermore, the overexpression of SNTB1 enhanced the proliferation, migration and invasion capacities of COAD cell lines. Caudal vein injection of COAD cells overexpressing SNTB1 in nude mice resulted in increased tumour growth and metastasis to the lung, liver and bone. Finally, single cell RNA-seq revealed alterations in the cellular subtypes of COAD, and CellphoneDB indicated that the interaction between cancer cells exhibiting high SNTB1 expression and enterocytes promoted EMT through cellular communications involving TGF-β, accelerating metastasis in COAD. Conclusion This study postulates that SNTB1 interacts with SRC to activate the Hippo-YAP pathway, thereby promoting COAD metastasis. Furthermore, cellular communication with enterocytes promotes EMT, facilitating metastasis. These findings propose novel therapeutic targets for preventing or treating metastatic COAD.

ObjectiveBurns lead to systemic changes manifested by systemic disturbances in water-electrolyte balance and systemic metabolic and inflammatory responses. The hypermetabolic response after a burn injury relies on metabolic, hormonal, and inflammatory dysregulation mechanisms. This study aimed to provide a comprehensive bibliometric analysis of the burn metabolism research field, identifying key trends, influential contributors, and emerging research hotspots to inform future investigative efforts. Ultimately, we conducted an extensive review of the literature, synthesizing the findings to clarify the present understanding within our field of study.MethodsWe obtained 8,823 scientific publications on burn injury and metabolism from the core Web of Science (WOS) database collection. In this work, biblioshiny was used to visualize and analyze the data, and VOSviewer was used to verify the results.ResultsFrom a total of 8,823 publications, we found a general upward trend in annual publications and citation frequency. According to Bradford’s Law, 21 high-production journals were classified as core sources based on the number of publications, and the most productive journal was Burns. The most published countries and authors in this field were the United States and Herndon DN. The most local cited document in this field was the article titled “Catecholamines: Mediator of the Hypermetabolic Response to Thermal Injury” authored by Wilmore DW. The thematic map showed that studies on injury, thermal injury, and sepsis were relatively mature. In contrast, research on metabolism, stress, and responses, and research on mortality, resistance, and management were less well-developed but were essential for the field.ConclusionResearch on burns and metabolism is increasing. Based on the bibliometric analysis, our study summarized the complex interplay between burn-induced systemic metabolic alterations and inflammatory responses, emphasizing the significance of hypermetabolism and its management. The role of propranolol, insulin, oxandrolone, and nutritional interventions in modulating the hypermetabolic state was discussed. Additionally, our study underscored the challenges of managing sepsis and drug-resistant infections in burn patients as an important future area of research.

Burn injuries often leave behind a “stasis zone”, a region of tissue critically important for determining both the severity of the injury and the potential for recovery. To understand the intricate cellular and epigenetic changes occurring within this critical zone, we utilized single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) to profile over 31,500 cells from both healthy rat skin and the stasis zone at nine different time points after a burn injury. This comprehensive approach revealed 26 distinct cell types and the dynamic shifts in the proportions of these cell types over time. We observed distinct gene activation patterns in different cell types at various stages post-burn, highlighting key players in immune activation, tissue regeneration, and blood vessel repair. Importantly, our analysis uncovered the regulatory networks governing these genes, offering valuable insights into the intricate mechanisms orchestrating burn wound healing. This comprehensive cellular and molecular atlas of the stasis zone provides a powerful resource for developing targeted therapies aimed at improving burn injury recovery and minimizing long-term consequences.

Abstract Background Medical school learning environment (MSLE) has a holistic impact on students’ psychosomatic health, academic achievements, and personal development. Students in different grades perceive MSLE in different ways. Thus, it is essential to investigate the specific role of student’s grade in the perception of MSLE. Methods Using the Johns Hopkins Learning Environment Scale (JHLES) as a quantification instrument for the perception level of MSLE, 10,901 medical students in 12 universities in China were categorized into low or high JHLES group according to their questionnaires. We investigated the relationship between student’s grade and JHLES category by univariate analysis employing Pearson Chi-square test and Welch’s ANOVA. Then multivariable logistic regression analysis confirmed the predictive efficacy of student’s grade. A nomogram concerning the prediction of low JHLES score probability in medical students was also constructed. Results A significant difference between two JHLES categories among students in different grades was observed (p

Abstract Background TSPAN7 is an important factor in tumor progression. However, the precise function of TSPAN7 and its role in pan-cancer are not clear. Methods Based on Xinhua cohort incorporating 370 patients with kidney neoplasm, we conducted differential expression analysis by immunohistochemistry between tumor and normal tissues, and explored correlations of TSPAN7 with patients’ survival. Subsequently, we conducted a pan-cancer study, and successively employed differential expression analysis, competing endogenous RNA (ceRNA) analysis, protein-protein interaction (PPI) analysis, correlation analysis of TSPAN7 with clinical characteristics, tumor purity, tumor genomics, tumor immunity, and drug sensitivity. Last but not least, gene set enrichment analysis was applied to identify enriched pathways of TSPAN7. Results In Xinhua cohort, TSPAN7 expression was significantly up-regulated (P-value = 0.0019) in tumor tissues of kidney neoplasm patients. High TSPAN7 expression was associated with decreases in overall survival (OS) (P-value = 0.009) and progression-free survival (P-value = 0.009), and it was further revealed as an independent risk factor for OS (P-value = 0.0326, HR = 5.66, 95%CI = 1.155–27.8). In pan-cancer analysis, TSPAN7 expression was down-regulated in most tumors, and it was associated with patients’ survival, tumor purity, tumor genomics, tumor immunity, and drug sensitivity. The ceRNA network and PPI network of TSPAN7 were also constructed. Last but not least, the top five enriched pathways of TSPAN7 in various tumors were identified. Conclusion TSPAN7 served as a promising biomarker of various tumors, especially kidney neoplasms, and it was closely associated with tumor purity, tumor genomics, tumor immunology, and drug sensitivity in pan-cancer level.

Abstract 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

Abstract Background Intervertebral disc degeneration (IVDD) is a common degenerative condition leading to abnormal stress distribution under load, causing intervertebral stenosis, facet joint degeneration, and foraminal stenosis. Very little is known about the molecular mechanism of eRNAs in IVDD. Methods Gene expression profiles of 38 annulus disc samples composed of 27 less degenerated discs (LDs) and 11 more degenerated discs (MDs) were retrieved from the GEO database. Then, differentially expressed enhancer RNAs (DEeRNAs), differentially expressed target genes (DETGs), and differentially expressed transcription factors (DETFs), hallmark of cancer signalling pathways according to GSVA; the types and quantity of immune cells according to CIBERSORT; and immune gene sets according to ssGSEA were analysed to construct an IVDD-related eRNA network. Then, multidimensional validation was performed to explore the interactions among DEeRNAs, DETFs and DEGs in space. Results A total of 53 components, 14 DETGs, 15 DEeRNAs, 3 DETFs, 5 immune cells, 9 hallmarks, and 7 immune gene sets, were selected to construct the regulatory network. After validation by online multidimensional databases, 21 interactive DEeRNA-DEG-DETF axes related to IVDD exacerbation were identified, among which the C1S-CTNNB1-CHD4 axis was the most significant. Conclusion Based upon the results of our study, we theorize that the C1S-CTNNB1-CHD4 axis plays a vital role in IVDD exacerbation. Specifically, C1S recruits CTNNB1 and upregulates the expression of CHD4 in IVDD, and subsequently, CHD4 suppresses glycolysis and activates oxidative phosphorylation, thus generating insoluble collagen fibre deposits and leading to the progression of IVDD. Overall, these DEeRNAs could comprise promising therapeutic targets for IVDD due to their high tissue specificity.

Summary: Spatial transcriptomics enables a single-cell resolution view of gene expression patterns in tissues, providing insight into their biological functions. However, applying this approach to the skin presents inherent challenges. Here, we present a protocol for preparing mammalian skin samples encompassing hair follicles for spatial transcriptomics. We describe steps for sample preparation, embedding, acquisition of frozen slices, RNA quality control, tissue mounting, fixation, staining, and imaging. We then detail procedures for permeabilization, reverse transcription, and cDNA collection.For complete details on the use and execution of this protocol, please refer to Chen et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

BackgroundStudy engagement is regarded important to medical students’ physical and mental wellbeing. However, the relationship between learning environment of medical schools and the study engagement of medical students was still unclear. This study was aimed to ascertain the positive effect of learning environment in study engagement.MethodsWe collected 10,901 valid questionnaires from 12 medical universities in China, and UWES-S was utilized to assess the study engagement levels. Then Pearson Chi-Square test and Welch’s ANOVA test were conducted to find the relationship between study engagement and learning environment, and subgroup analysis was used to eradicate possible influence of confounding factors. After that, a multivariate analysis was performed to prove learning environment was an independent factor, and we constructed a nomogram as a predictive model.ResultsWith Pearson Chi-Square test (p

Abstract 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

Abstract Background With increasing detection of small renal masses and accumulating evidence that nephron sparing surgery (NSS) could achieve oncological equivalence and functional superiority compared with radical nephrectomy (RN), NSS has become first‐line therapy for some patients with localized renal masses. Objective This study aims to review the publications in the kidney neoplasm and NSS field, exploring the research hotspots. Method Kidney neoplasm and NSS related publications before July 3th 2023 were obtained from the Web of Science Core Collection database. We then used bibliometric analysis to conduct performance analysis, citation analysis and co‐citation network of publications, together with keyword co‐occurrence analysis. Results Seven thousand five hundred and sixty‐four documents were finally retrieved, and the annual publications increased exponentially. The most productive authors were “KAOUK JH” and “GILL IS”, while USA, and 12 American affiliations such as CLEVELAND CLINIC FOUNDATION and MAYO CLINIC were far leading in this field. Journal of Urology and European Urology were journals with the highest citations and h‐index. Discussion Through literature reviewing plus co‐occurrence and clustering analysis, the therapeutic effects of partial nephrectomy (PN) versus RN on patients with localized renal cell carcinoma, different operative approaches of PN, and conservative NSS methods were deemed as the most focused topics. Conclusion Three aspects were the most important hotspots in this field. Firstly, how to provide the optimal management choices for different patients. Secondly, therapeutic effects of different management options and surgical techniques needed more prospective and randomized studies. Finally, more novel technologies and surgical techniques were required.

Background: The reclassification of Papillary Thyroid Carcinoma (PTC) is an area of research that warrants attention. The connection between thyroid cancer, inflammation, and immune responses necessitates considering the mechanisms of differential prognosis of thyroid tumors from an immunological perspective. Given the high adaptability of macrophages to environmental stimuli, focusing on the differentiation characteristics of macrophages might offer a novel approach to address the issues related to PTC subtyping. Methods: Single-cell RNA sequencing data of medullary cells infiltrated by papillary thyroid carcinoma obtained from public databases was subjected to dimensionality reduction clustering analysis. The RunUMAP and FindAllMarkers functions were utilized to identify the gene expression matrix of different clusters. Cell differentiation trajectory analysis was conducted using the Monocle R package. A complex regulatory network for the classification of Immune status and Macrophage differentiation-associated Papillary Thyroid Cancer Classification (IMPTCC) was constructed through quantitative multi-omics analysis. Immunohistochemistry (IHC) staining was utilized for pathological histology validation. Results: Through the integration of single-cell RNA and bulk sequencing data combined with multi-omics analysis, we identified crucial transcription factors, immune cells/immune functions, and signaling pathways. Based on this, regulatory networks for three IMPTCC clusters were established. Conclusion: Based on the co-expression network analysis results, we identified three subtypes of IMPTCC: Immune-Suppressive Macrophage differentiation-associated Papillary Thyroid Carcinoma Classification (ISMPTCC), Immune-Neutral Macrophage differentiation-associated Papillary Thyroid Carcinoma Classification (INMPTCC), and Immune-Activated Macrophage differentiation-associated Papillary Thyroid Carcinoma Classification (IAMPTCC). Each subtype exhibits distinct metabolic, immune, and regulatory characteristics corresponding to different states of macrophage differentiation.

BackgroundProstate cancer (PCa) is one of the most threatening health problems for the elderly males. However, our understanding of the disease has been limited by the research technology for a long time. Recently, the maturity of sequencing technology and omics studies has been accelerating the studies of PCa, establishing themselves as an essential impetus in this field.MethodsWe assessed Web of Science (WoS) database for publications of sequencing and omics studies in PCa on July 3rd, 2023. Bibliometrix was used to conduct ulterior bibliometric analysis of countries/affiliations, authors, sources, publications, and keywords. Subsequently, purposeful large amounts of literature reading were proceeded to analyze research hotspots in this field.Results3325 publications were included in the study. Research associated with sequencing and omics studies in PCa had shown an obvious increase recently. The USA and China were the most productive countries, and harbored close collaboration. CHINNAIYAN AM was identified as the most influential author, and CANCER RESEARCH exhibited huge impact in this field. Highly cited publications and their co-citation relationships were used to filtrate literatures for subsequent literature reading. Based on keyword analysis and large amounts of literature reading, ‘the molecular pathogenesis of PCa’ and ‘the clinical application of sequencing and omics studies in PCa’ were summarized as two research hotspots in the field.ConclusionSequencing technology had a deep impact on the studies of PCa. Sequencing and omics studies in PCa helped researchers reveal the molecular pathogenesis, and provided new possibilities for the clinical practice of PCa.

Conclusion: The present study obtained deep insight into the developing trends and research hotspots on burns associated with stem cells, which arouses growing concerns and implies increasing clinical implications. The mechanism and therapeutics of epidermal stem cells (ESCs) for burn wounds and the mechanism of mesenchymal stem cells (MSCs) and MSC-derived exosomes for burns wounds are two research hotspots in this field.

Conclusion: Our findings provide valuable insights into the developing trends and key areas of research on RBPs in trauma and burns. Notably, we identified two primary hotspots: RBPs in the pathophysiological mechanisms of various traumatic injuries and RBPs in the processes of cutaneous wound healing. This rapidly evolving field offers significant reference points for scientific researchers and clinical practitioners.

Abstract Objectives Lymphocyte activation gene 3 (LAG3), an inhibitory receptor in T‐cell activation, is a negative prognostic factor. However, its impact on tumours has yet to be comprehensively elucidated on a pan‐cancer scale. Thus, we aim to reveal its role at the pan‐cancer level. Methods We performed IHC staining on a retrospective cohort of 370 patients. Then we assessed the prognostic effect of LAG3 using Kaplan–Meier survival analysis and multivariate Cox regression analysis. In pan‐cancer analysis, we constructed competing endogenous RNA and protein–protein interaction networks, conducted gene set enrichment analysis and identified correlations between LAG3 gene expression and various factors, including clinical characteristics, tumour purity, mutations, tumour immunity and drug sensitivity across 33 cancer types. Results LAG3 was expressed higher in normal kidney tissues than in tumours. A high level of LAG3 gene expression was an independent prognostic factor for OS (HR = 6.60, 95% CI = 2.43–17.90, P

Abstract Spinal cord injury (SCI) remains a severe condition with an extremely high disability rate. The challenges of SCI repair include its complex pathological mechanisms and the difficulties of neural regeneration in the central nervous system. In the past few decades, researchers have attempted to completely elucidate the pathological mechanism of SCI and identify effective strategies to promote axon regeneration and neural circuit remodeling, but the results have not been ideal. Recently, new pathological mechanisms of SCI, especially the interactions between immune and neural cell responses, have been revealed by single-cell sequencing and spatial transcriptome analysis. With the development of bioactive materials and stem cells, more attention has been focused on forming intermediate neural networks to promote neural regeneration and neural circuit reconstruction than on promoting axonal regeneration in the corticospinal tract. Furthermore, technologies to control physical parameters such as electricity, magnetism and ultrasound have been constantly innovated and applied in neural cell fate regulation. Among these advanced novel strategies and technologies, stem cell therapy, biomaterial transplantation, and electromagnetic stimulation have entered into the stage of clinical trials, and some of them have already been applied in clinical treatment. In this review, we outline the overall epidemiology and pathophysiology of SCI, expound on the latest research progress related to neural regeneration and circuit reconstruction in detail, and propose future directions for SCI repair and clinical applications.

Abstract Subclassification of tumors based on molecular features may facilitate therapeutic choice and increase the response rate of cancer patients. However, the highly complex cell origin involved in osteosarcoma (OS) limits the utility of traditional bulk RNA sequencing for OS subclassification. Single-cell RNA sequencing (scRNA-seq) holds great promise for identifying cell heterogeneity. However, this technique has rarely been used in the study of tumor subclassification. By analyzing scRNA-seq data for six conventional OS and nine cancellous bone (CB) samples, we identified 29 clusters in OS and CB samples and discovered three differentiation trajectories from the cancer stem cell (CSC)-like subset, which allowed us to classify OS samples into three groups. The classification model was further examined using the TARGET dataset. Each subgroup of OS had different prognoses and possible drug sensitivities, and OS cells in the three differentiation branches showed distinct interactions with other clusters in the OS microenvironment. In addition, we verified the classification model through IHC staining in 138 OS samples, revealing a worse prognosis for Group B patients. Furthermore, we describe the novel transcriptional program of CSCs and highlight the activation of EZH2 in CSCs of OS. These findings provide a novel subclassification method based on scRNA-seq and shed new light on the molecular features of CSCs in OS and may serve as valuable references for precision treatment for and therapeutic development in OS.

ABSTRACT Gut microbiota can regulate many physiological processes within gastrointestinal tract and other distal sites. Dysbiosis may not only influence chronic diseases like the inflammatory bowel disease (IBD), metabolic disease, tumor and its therapeutic efficacy, but also deteriorate acute injuries. This article aims to review the documents in this field and summarize the research hotspots as well as developing processes. Gut microbiota and immune microenvironment-related documents from 1976 to 2022 were obtained from the Web of Science Core Collection database. Bibliometrics was used to assess the core authors and journals, most contributive countries and affiliations together with hotspots in this field and keyword co-occurrence analysis. Data were visualized to help comprehension. Nine hundred and twelve documents about gut microbiota and immune microenvironment were retrieved, and the annual publications increased gradually. The most productive author, country, and affiliation were “Zitvogel L,” USA and “UNIV TEXAS MD ANDERSON CANC CTR,” respectively. FRONTIERS IN IMMUNOLOGY, CANCERS, and INTERNATIONAL JOURNAL OF MOLECULAR SCIENCE were the periodicals with most publications. Keyword co-occurrence analysis identified three clusters, including gut microbiota, inflammation, and IBD. Combined with the visualized analysis of documents and keyword co-occurrence as well as literature reading, we recognized three key topics of gut microbiota: cancer and therapy; immunity, inflammation and IBD; acute injuries and metabolic diseases. This article revealed researches on gut microbiota and immune microenvironment were growing. More attention should be given to the latest hotspots like gut microbiota, inflammation, IBD, cancer and immunotherapy, acute traumas, and metabolic diseases. IMPORTANCE Gut microbiota can regulate many physiological processes within gastrointestinal tract and other distal sites. Dysbiosis may not only influence chronic diseases like inflammatory bowel disease (IBD), metabolic disease, tumor and its therapeutic efficacy, but also deteriorate acute injuries. While the application of bibliometrics in the field of gut microbiota and immune microenvironment still remains blank, which focused more on the regulation of the gut microbiota on the immune microenvironment of different kinds of diseases. Here, we intended to review and summarize the presented documents in gut microbiota and immune microenvironment field by bibliometrics. And we revealed researches on gut microbiota and immune microenvironment were growing. More attention should be given to the latest hotspots like gut microbiota, inflammation, IBD, cancer and immunotherapy, acute traumas, and metabolic diseases.

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.

Alzheimer's disease (AD) is a typical neurodegenerative disease that leads to irreversible neuronal degeneration, and effective treatment remains elusive due to the unclear mechanism. We utilized biocompatible mesenchymal stem cell-derived extracellular vesicles as carriers loaded with the CB2 target medicine AM1241 (EVs-AM1241) to protect against neurodegenerative progression and neuronal function in AD model mice. According to the results, EVs-AM1241 were successfully constructed and exhibited better bioavailability and therapeutic effects than bare AM1241. The Morris water maze (MWM) and fear conditioning tests revealed that the learning and memory of EVs-AM1241-treated model mice were significantly improved. In vivo electrophysiological recording of CA1 neurons indicated enhanced response to an auditory conditioned stimulus following fear learning. Immunostaining and Western blot analysis showed that amyloid plaque deposition and amyloid β (Aβ)-induced neuronal apoptosis were significantly suppressed by EVs-AM1241. Moreover, EVs-AM1241 increased the number of neurons and restored the neuronal cytoskeleton, indicating that they enhanced neuronal regeneration. RNA sequencing revealed that EVs-AM1241 facilitated Aβ phagocytosis, promoted neurogenesis and ultimately improved learning and memory through the calcium-Erk signaling pathway. Our study showed that EVs-AM1241 efficiently reversed neurodegenerative pathology and enhanced neurogenesis in model mice, indicating that they are very promising particles for treating AD.

Abstract Alternative splicing (AS) is common in gene expression, and abnormal splicing often results in several cancers. Overall survival-associated splicing events (OS-SEs) have been used to predict prognosis in cancer. The aim of this study was to investigate the presence and function of OS-SEs in uterine corpus endometrial carcinoma (UCEC). Based on TCGA and TCGASpliceSeq databases, gene expression and the AS data of UCEC samples were retrieved. An alternate terminator of ANKHD1 transcripts named ANKHD1-BP3 was found to be significantly related to metastasis and OS in UCEC and significantly associated with HSPB1. The upregulated expression of HSPB1 induced downregulation of ANKHD1-BP3 and promoted tumor metastasis. These findings indicate that HSPB1, a splicing factor, regulates the expression of ANKHD1-BP3 to promote metastasis in UCEC.

BackgroundDiabetic foot ulcers (DFUs) are one of the most popular and severe complications of diabetes. The persistent non-healing of DFUs may eventually contribute to severe complications such as amputation, which presents patients with significant physical and psychological challenges. Fibroblasts are critical cells in wound healing and perform essential roles in all phases of wound healing. In diabetic foot patients, the disruption of fibroblast function exacerbates the non-healing of the wound. This study aimed to summarize the hotspots and evaluate the global research trends on fibroblast-related DFUs through bibliometric analysis.MethodsScientific publications on the study of fibroblast-related DFUs from January 1, 2000 to April 27, 2022 were retrieved from the Web of Science Core Collection (WoSCC). Biblioshiny software was primarily performed for the visual analysis of the literature, CiteSpace software and VOSviewer software were used to validate the results.ResultsA total of 479 articles on fibroblast-related DFUs were retrieved. The most published countries, institutions, journals, and authors in this field were the USA, The Chinese University of Hong Kong, Wound Repair and Regeneration, and Seung-Kyu Han. In addition, keyword co-occurrence networks, historical direct citation networks, thematic map, and the trend topics map summarize the research hotspots and trends in this field.ConclusionCurrent studies indicated that research on fibroblast-related DFUs is attracting increasing concern and have clinical implications. The cellular and molecular mechanisms of the DFU pathophysiological process, the molecular mechanisms and therapeutic targets associated with DFUs angiogenesis, and the measures to promote DFUs wound healing are three worthy research hotspots in this field.

Abstract Spinal cord injury (SCI) involves diverse injury responses in different cell types in a temporally and spatially specific manner. Here, using single-cell transcriptomic analyses combined with classic anatomical, behavioral, electrophysiological analyses, we report, with single-cell resolution, temporal molecular and cellular changes in crush-injured adult mouse spinal cord. Data revealed pathological changes of 12 different major cell types, three of which infiltrated into the spinal cord at distinct times post-injury. We discovered novel microglia and astrocyte subtypes in the uninjured spinal cord, and their dynamic conversions into additional stage-specific subtypes/states. Most dynamic changes occur at 3-days post-injury and by day-14 the second wave of microglial activation emerged, accompanied with changes in various cell types including neurons, indicative of the second round of attacks. By day-38, major cell types are still substantially deviated from uninjured states, demonstrating prolonged alterations. This study provides a comprehensive mapping of cellular/molecular pathological changes along the temporal axis after SCI, which may facilitate the development of novel therapeutic strategies, including those targeting microglia.

Background: The signal transducer and activator of transcription (STAT) gene family have been widely found to regulate cell proliferation, differentiation, apoptosis, and angiogenesis through complex signaling pathways, and thus impacting tumor formation and development in different types of tumor. However, the roles of STATs on prognostic prediction and therapeutic guidance in pan-cancer remain unexplored.Materials and Methods: The dataset of 33 types of TCGA tumor, para-carcinoma and normal tissues, was obtained from the UCSC Xena database, including the gene expression profiles in the formats of FPKM value, demographic characteristics, clinical information, and survival data of STATs. Differential expression and co-expression analyses, WGCNA, clinical relevance analysis, immune subtype analysis, tumor stemness analysis, tumor purity analysis, immune infiltration analysis, immunotherapy related analysis, tumor mutation related analysis, and drug sensitivity analysis were performed by R software.Results: Differential expression of STAT1 was found between normal and BRCA tissues (p < 0.001, log2FC = 0.895). Additionally, the strongest correlation among STATs lied between STAT1 and STAT2 (correlation coefficient = 0.6). Moreover, high expression levels of STAT1 (p = 0.031) were revealed to be notably correlated with poor prognosis in KIRP. In addition, STAT1 expressed the highest value in immune subtypes C1, C2, C3, and C6 in LUAD. What’s more, strong negative correlations were demonstrated between expression of STAT6 and mDNAss and mRNAss of TGCT. Additionally, STAT4 expression was characterized to be significantly negatively correlated with tumor purity of the majority of cancer types. Moreover, STAT1 and STAT3 were shown to be generally high-expressed in pan-cancer myeloid cells, and STATs all had positive correlation with the infiltration of the majority of immune cells. In addition, STATs were revealed to be closely linked with immunotherapy response. What’s more, STAT4 expression was identified to have a strong negative correlation with TMB value in DLBC. Last but not least, positive correlations were accessed between STAT5 and sensitivity of Nelarabine (cor = 0.600, p < 0.001).Conclusion: In the present study, we identified STATs as biomarkers for prognostic prediction and therapeutic guidance in pan-cancer. Hopefully our findings could provide a valuable reference for future STATs research and clinical applications.

IntroductionOver 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.MethodsWe retrieved relevant documents and their published information from the Web of Science Core Collection (WoSCC). Bibliometrix package was responsible for the visualized analysis.ResultsTotally, 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.DiscussionThe 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.

BackgroundRheumatoid 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.MethodsWe 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.ResultsFrom 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.ConclusionThe 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.

BackgroundRheumatism 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.MethodsArticles 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.ResultsThe 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.ConclusionsSequencing 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.

BackgroundRheumatic diseases (RD) are a group of multi-system inflammatory autoimmune diseases whose causes are still under study. In the past few decades, researchers have found traces of the association between rheumatic diseases and intestinal microbiota, which can partially explain the pathogenesis of rheumatic diseases. We aimed to describe the research trend and main divisions on how gut flora interreacts with rheumatic diseases, and discussed about the possible clinical applications.MethodsWe analyzed bibliometric data from the Web of Science core collection (dated 15th May 2022). Biblioshiny R language software packages (bibliometrix) were used to obtain the annual publication and citations, core sources according to Bradford’s law, and country collaboration map. We designed and verified the keyword co-occurrence network and strategic diagram with the help of VOSviewer and CiteSpace, subdivided the research topic into several themes and identified research dimensions. The tables of most local cited documents and core sources were processed manually. Furthermore, the Altmetric Attention Score and the annual Altmetric Top 100 were applied to analyze the annual publication and citation.ResultsFrom a total of 541 documents, we found that the overall trend of annual publication and citation is increasing. The major research method is to compare the intestinal microbial composition of patients with certain rheumatic disease and that of the control group to determine microbial alterations related to the disease’s occurrence and development. According to Bradford’s law, the core sources are Arthritis and Rheumatology, Annals of the Rheumatic Diseases, Current Opinion in Rheumatology, Nutrients, Rheumatology, and Journal of Rheumatology. Since 1976, 101 countries or regions have participated in studies of rheumatology and intestinal microbes. The United States ranks at the top and has the broadest academic association with other countries. Five themes were identified, including the pivotal role of inflammation caused by intestinal bacteria in the rheumatic pathogenesis, the close relationship between rheumatic diseases and inflammatory bowel disease, immunoregulation mechanism as a mediator of the interaction between rheumatic diseases and gut flora, dysbiosis and decreased diversity in intestine of patients with rheumatic diseases, and the influence of oral flora on rheumatic diseases. Additionally, four research dimensions were identified, including pathology, treatment, disease, and experiments.ConclusionStudies on rheumatic diseases and the intestinal microbiota are growing. Attention should be paid to the mechanism of their interaction, such as the microbe-immune-RD crosstalk. Hopefully, the research achievements can be applied to diseases’ prevention, diagnosis, and treatment, and our work can contribute to the readers’ future research.

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

BackgroundSpinal 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.MethodsPublications 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.ResultsAmong 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.ConclusionAs 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.

Abstract Background The coronavirus disease 2019 (COVID-19) has induced a worldwide epidemiological event with a high infectivity and mortality. However, the predicting biomarkers and their potential mechanism in the progression of COVID-19 are not well known. Objective The aim of this study is to identify the candidate predictors of COVID-19 and investigate their underlying mechanism. Methods The retrospective study was conducted to identify the potential laboratory indicators with prognostic values of COVID-19 disease. Then, the prognostic nomogram was constructed to predict the overall survival of COVID-19 patients. Additionally, the scRNA-seq data of BALF and PBMCs from COVID-19 patients were downloaded to investigate the underlying mechanism of the most important prognostic indicators in lungs and peripherals, respectively. Results In total, 304 hospitalized adult COVID-19 patients in Wuhan Jinyintan Hospital were included in the retrospective study. CEA was the only laboratory indicator with significant difference in the univariate (P

Abstract Mesothelioma (MESO) is an infrequent tumor derived from mesothelial cells of pleura, peritoneum, pericardium, and tunica vaginalis testis. Despite advancement in technologies and better understanding of tumor progression mechanism, the prognosis of MESO remains poor. The role of alternative splicing events (ASEs) in the oncogenesis, tumor metastasis and drug resistance has been widely discussed in multiple cancers. But the prognosis and potential therapeutic value of ASEs in MESO were not clearly studied by now. We constructed a prognostic model using RNA sequencing data and matched ASE data of MESO patients obtained from the TCGA and TCGASpliceSeq database. A total of 3,993 ASEs were identified associated with overall survival using Cox regression analysis. Eight of them were finally figured out to institute the model by lasso regression analysis. The risk score of the model can predict the prognosis independently. Among the identified 390 splicing factors (SF), HSPA1A and DDX3Y was significantly associated with 43 OS‐SEs. Among these OS‐SEs, SNX5‐58744‐AT (p = 0.048) and SNX5‐58745‐AT (p = 0.048) were significantly associated with bone metastasis. Co‐expression analysis of signal pathways and SNX5‐58744‐AT, SNX5‐58745‐AT was also depicted using GSVA. Finally, we proposed that splicing factor (SF) HSPA1A could regulate SNX5‐58744‐AT (R = −0.414) and SNX5‐58745‐AT (R = 0.414) through the pathway “Class I MHC mediated antigen processing and presentation” (R = 0.400). In this way, tumorigenesis and bone metastasis of MESO were controlled.

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.

BackgroundThe interleukin-17 (IL-17) family contains six homologous genes, IL-17A to IL-17F. Growing evidence indicates that dysregulated IL-17 family members act as major pathogenic factors in the early and late stages of cancer development and progression. However, the prevalence and predictive value of IL-17 for immune checkpoint inhibitor (ICI) therapeutic effectiveness in multiple tumor types remain largely unknown, and the associations between its expression levels and immunotherapy-associated signatures also need to be explored.MethodsThe pan-cancer dataset in The Cancer Genome Atlas (TCGA) was downloaded from UCSC Xena (http://xena.ucsc.edu/). The immunotherapeutic cohorts included IMvigor210, which were obtained from the Gene Expression Omnibus database and included in a previously published study. Other datasets, namely, the GEO dataset and PRECOG, GEO, and METABRIC databases, were also included. In 33 TCGA tumor types, a pan-cancer analysis was carried out including their expression map, clinical risk assessment, and immune subtype analysis, along with their association with the stemness indices, tumor microenvironment (TME) in pan-cancer, immune infiltration analysis, ICI-related immune indicators, and drug sensitivity. RT-PCR was also carried out to verify the gene expression levels among MCF-10A and MCF-7 cell lines.ResultsThe expression of the IL-17 family is different between tumor and normal tissue in most cancers, and consistency has been observed between gene activity and gene expression. RT-PCR results show that the expression differences in the IL-17 family of human cell (MCF-10A and MCF-7) are consistent with the bioinformatics differential expression analysis. Moreover, the expression of the IL-17 family can be a sign of patients’ survival prognosis in some tumors and varies in different immune subtypes. Moreover, the expression of the IL-17 family presents a robust correlation with immune cell infiltration, ICI-related immune indicators, and drug sensitivity. High expression of the IL-17 family is significantly related to immune-relevant pathways, and the low expression of IL-17B means a better immunotherapeutic response in BLCA.ConclusionCollectively, IL-17 family members may act as biomarkers in predicting the prognosis of the tumor and the therapeutic effects of ICIs, which provides new guidance for cancer treatment.

BackgroundChordoma is a type of mesenchymal malignancy with a high recurrence rate and poor prognosis. Due to its rarity, the tumorigenic mechanism and optimal therapeutic strategy are not well known.MethodsAll relevant articles of chordoma research from 1 January 2000 to 26 April 2022 were obtained from Web of Science Core Collection database. Blibliometrix was used to acquire basic publication data. Visualization and data table of collaboration network, dynamic analysis, trend topics, thematic map, and factorial analysis were acquired using Blibliometrix package. VOSviewer was used to generate a visualization map of co-citation analysis and co-occurrence.ResultsA total of 2,285 articles related to chordoma were identified. The most influential and productive country/region was the United States, and Capital Medical University has published the most articles. Among all high-impact authors, Adrienne M. Flanagan had the highest average citation rate. Neurosurgery was the important periodical for chordoma research with the highest total/average citation rate. We focused on four hotspots in recent chordoma research. The research on surgical treatment and radiotherapy was relatively mature. The molecular signaling pathway, targeted therapy and immunotherapy for chordoma are not yet mature, which will be the future trends of chordoma research.ConclusionThis study indicates that chordoma studies are increasing. Surgery and radiotherapy are well reported and always play fundamental roles in chordoma treatment. The molecular signaling pathway, targeted therapy, and immunotherapy of chordoma are the latest research hotspots.

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.

Summary: 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.

Abstract Background Soft tissue sarcomas (STS) has a high rate of early metastasis. In this study, we aimed to uncover the potential metastasis mechanisms and related signaling pathways in STS with differentially expressed genes and tumor-infiltrating cells. Methods RNA-sequencing (RNA-seq) of 261 STS samples downloaded from the Cancer Genome Atlas (TCGA) database were used to identify metastasis-related differentially expressed immune genes and transcription factors (TFs), whose relationship was constructed by Pearson correlation analysis. Metastasis-related prediction model was established based on the most significant immune genes. CIBERSORT algorithm was performed to identify significant immune cells co-expressed with key immune genes. The GSVA and GSEA were performed to identify prognosis-related KEGG pathways. Ultimately, we used the Pearson correlation analysis to explore the relationship among immune genes, immune cells, and KEGG pathways. Additionally, key genes and regulatory mechanisms were validated by single-cell RNA sequencing and ChIP sequencing data. Results A total of 204 immune genes and 12 TFs, were identified. The prediction model achieved a satisfactory effectiveness in distant metastasis with the Area Under Curve (AUC) of 0.808. LTB was significantly correlated with PAX5 (P

Abstract Background Maternal vitamin D deficiency has been a worldwide concern in recent years. However the epidemiological data of vitamin D deficiency among large group of Chinese pregnant women is limited. This study is to evaluate the prevalence of vitamin D deficiency among pregnant women in Shanghai, China and to analyze the association of vitamin D status with some pregnancy outcomes (gestational diabetes and low birth weight). Methods A total of 34,417 pregnant women in Shanghai were included in this study from January 2014 to December 2017, and the serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured at 16th week of gestation by electrochemiluminescence assay. Seventy five grams of glucose was used to conduct oral glucose tolerance test during 24-28th week of gestational in all enrolled persons and the birth weight of newborns was recorded. Results The median serum 25(OH) D concentration in the pregnant women during 4 years was 42.87 nmol/L (32.88–51.90 nmol/L). 9.9% of the population were severe vitamin D deficient [25(OH)D

Medical students' perceptions of the medical school learning environment (MSLE) have an important impact on their professional development, and physical and mental health. Few studies reported potential factors that influenced medical students' perceptions of MSLE. Thus, the main goal of this study was to identify influencing factors for medical students' perception levels of MSLE. The perception levels of MSLE were assessed by the Johns Hopkins Learning Environment Scale. The univariate and multivariate logistic regression analyses were performed to identify significant predictors for the perceptions of MSLE. The nomograms were established to predict medical students' perception levels of MSLE. In the multivariate logistic regression model, gender, university category, grade, mother education level, learning environment of schools, interests in medicine, and Kolb learning experience were significantly associated with medical students' perceptions of MSLE. Correspondently, the nomograms were built based on significant variables identified by the univariate logistic regression analysis. The validation of the nomograms showed that the model had promising predictive accuracy, discrimination, and accordance (area under the curve (AUC) = 0.751). This study identified influencing factors of medical students' perceptions of MSLE. It is essential to implement corresponding interventions to improve medical students' perceptions.

Skin cutaneous melanoma (SKCM) is a type of highly invasive cancer originated from melanocytes. It is reported that aberrant alternative splicing (AS) plays an important role in the neoplasia and metastasis of many types of cancer. Therefore, we investigated whether ASEs of pre-RNA have such an influence on the prognosis of SKCM and the related mechanism of ASEs in SKCM. The RNA-seq data and ASEs data for SKCM patients were obtained from the TCGA and TCGASpliceSeq database. The univariate Cox regression revealed 1265 overall survival-related splicing events (OS-SEs). Screened by Lasso regression, 4 OS-SEs were identified and used to construct an effective prediction model (AUC: .904), whose risk score was proved to be an independent prognostic factor. Furthermore, Kruskal–Wallis test and Mann–Whitney–Wilcoxon test showed that an aberrant splicing type of aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2) regulated by CDC-like kinase 1 (CLK1) was associated with the metastasis and stage of SKCM. Besides, the overlapped signal pathway for AIMP2 was galactose metabolism identified by the co-expression analysis. External database validation also confirmed that AIMP2, CLK1, and the galactose metabolism were associated with the metastasis and stage of SKCM patients. ChIP-seq and ATAC-seq methods further confirmed the transcription regulation of CLK1, AIMP2, and other key genes, whose cellular expression was detected by Single Cell Sequencing. In conclusion, we proposed that CLK1-regulated AIMP2-78704-ES might play a critical role in the tumorigenesis and metastasis of SKCM via galactose metabolism. Besides, we established an effective model with MTMR14-63114-ES, URI1-48867-ES, BATF2-16724-AP, and MED22-88025-AP to predict the metastasis and prognosis of SKCM patients.

Background: Spinal cord injury (SCI) is a severe neurological deficit affecting both young and older people worldwide. The potential role of key enhancer RNAs (eRNAs) in SCI remains elusive, which is a prominent challenge in the trauma repair process. This study aims to investigate the roles of key eRNAs, transcription factors (TFs), signaling pathways, and small-molecule inhibitors in SCI using multi-omics bioinformatics analysis.Methods: Microarray data of peripheral blood mononuclear cell (PBMC) samples from 27 healthy volunteers and 25 chronic-phase SCI patients were retrieved from the Gene Expression Omnibus database. Differentially expressed transcription factors (DETFs), differentially expressed enhancer RNAs (DEeRNAs), and differentially expressed target genes (DETGs) were identified using the Linear Models for Microarray Data (limma) package. Fraction of immune cells was estimated using CIBERSORT algorithm. Gene Set Variation Analysis (GSVA) was applied to identify the downstream signaling pathways. The eRNA regulatory network was constructed based on the correlation results. Connectivity Map (CMap) database was used to find potential drugs for SCI patients. The cellular communication analysis was performed to explore the molecular regulation mechanism of SCI based on single-cell RNA sequencing (scRNA-seq) data. Chromatin immunoprecipitation sequencing (ChIP-seq) and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) data were used to validate the key regulatory mechanisms. scRNA-seq dataset was used to validate the cell subtype localization of the key eRNAs.Results: In total, 21 DETFs, 24 DEeRNAs, and 829 DETGs were identified. A regulatory network of 13 DETFs, six DEeRNAs, seven DETGs, two hallmark pathways, two immune cells, and six immune pathways was constructed. The link of Splicing factor proline and glutamine rich (SFPQ) (TF) and vesicular overexpressed in cancer prosurvival protein 1 (VOPP1) (eRNA) (R = 0.990, p < 0.001, positive), VOPP1 (eRNA) and epidermal growth factor receptor (EGFR) (target gene) (R = 0.974, p < 0.001, positive), VOPP1, and T helper (Th) cells (R = −0.987, p < 0.001, negative), and VOPP1 and hallmark coagulation (R = 0.937, p < 0.001, positive) was selected. Trichostatin A was considered the best compound target to SCI-related eRNAs (specificity = 0.471, p < 0.001).Conclusion: VOPP1, upregulated by SFPQ, strengthened the transient expression of EGFR. Th cells and coagulation were the potential downstream pathways of VOPP1. This regulatory network and potential inhibitors provide novel diagnostic biomarkers and therapeutic targets for SCI.

Objective To identify prognostic factors and establish nomograms for predicting overall survival (OS) and cause specific survival (CSS) of patients with non‐metastatic chondrosarcoma. Methods We collected information on patients with non‐metastatic chondrosarcoma from the Surveillance, Epidemiology, and End Results (SEER) database between 2005 and 2014, together with data from the First Affiliated Hospital of Zhengzhou University from 2011 to 2016. Variables including patients’ baseline demographics (age, race, and gender), tumor characteristics (tumor size and extension, histology subtype, primary site, and American Joint Committee on Cancer [AJCC] stage), therapy (surgery, chemotherapy, and radiotherapy), and socioeconomic status (SES) were extracted for further analysis. OS and CSS were retrieved as our researching endpoints. Patients from the database were regarded as the training set, and univariate analysis, Lasso regression and multivariate analysis as well as the random forest were used to explore the predictors and establish nomograms. To validate nomograms internally and externally, we applied bootstrapped validation internally with the training dataset, while the dataset for external validation was obtained from the First Affiliated Hospital of Zhengzhou University. We estimated the discriminative ability of nomograms based on Cox proportional hazard regression models by means of calibration curves and the concordance index (C‐index) of internal and external validation. Results After the implementation of exclusion criteria, there were 1267 patients in the training set and 72 patients in the testing set with non‐metastatic chondrosarcomas. Age, gender, grade, histological subtype, primary site, surgery, radiation, chemotherapy, being employed/unemployed, tumor size, and tumor extension were significantly associated with prognosis in the univariate analysis. Age, gender, tumor size and extension, primary site, surgery, radiotherapy, chemotherapy, histological grade, and subtype were independent prognostic factors in the Cox models. The C‐index of nomograms (internal: OS, 0.787; CSS, 0.821; external: OS, 0.777; CSS, 0.821) were higher than following conventional systems: AJCC sixth (OS, 0.640; CSS, 0.673) and seventh edition (OS, 0.675; CSS, 0.711). Conclusions Age, gender, tumor size and extension, surgery, histological grade, and subtype were independent prognostic factors for both OS and CSS. In addition, we revealed that chondrosarcomas in the trunk, radiotherapy, and chemotherapy were correlated with poor prognosis. Our nomograms based on significant clinicopathologic features can well predict the 3‐year and 5‐year survival probability of patients with non‐metastatic chondrosarcoma and assist oncologists in making accurate survival evaluation.

ObjectiveCancer pain, the most common skeleton-related event of bone metastases, significantly disturbs patients’ life. MRI-guided focused ultrasound (MRgFUS) is a therapeutic option to relieve pain; however, its efficacy and safety have not been fully explored. Therefore, we aim to conduct a meta-analysis on studies reporting MRgFUS for patients with bone metastases.MethodsRandomized controlled trials (RCT) and non-RCTs on MRgFUS treatment for patients with bone metastases were collected using PubMed, MEDLINE In-Process (US National Library of Medicine), National Institutes of Health (US National Library of Medicine), Embase (Elsevier), Web of Science, CINAHL, and the Cochrane Library between August 2007 and September 2019. Data on quantitative pain assessment before/after MRgFUS, response rate, and complication were extracted and analyzed.ResultsFifteen eligible studies with 362 patients were selected in this meta-analysis. The average pain score was 6.74 (95% CI: 6.30–7.18) at baseline, 4.15 (95% CI: 3.31–4.99) at 0–1 week, 3.09 (95% CI: 2.46–3.72) at 1–5 weeks, and 2.28 (95% CI: 1.37–3.19) at 5–14 weeks. Compared with baseline, the pain improvement at 0–1 week was 2.54 (95% CI: 1.92–3.16, p < 0.01), at 1–5 weeks was 3.56 (95% CI: 3.11–4.02, p < 0.01), and at 5–14 weeks was 4.22 (95% CI: 3.68–4.76, p < 0.01). Change from baseline in OMEDD at 2 weeks after treatment was −15.11 (95% CI: −34.73, 4.50), at 1 month after treatment was −10.87 (95% CI: −26.32, 4.58), and at 3 months after treatment was −5.53 (95% CI: −20.44, 9.38). The overall CR rate was 0.36 (95% CI: 0.24–0.48), PR rate was 0.47 (95% CI: 0.36–0.58), and NR rate was 0.23 (95% CI: 0.13–0.34). Among 14 studies including 352 patients, 93 (26.4%) patients with minor complications and 5 (1.42%) patients with major complications were recorded.ConclusionThis meta-analysis identifies MRgFUS as a reliable therapeutic option to relieve cancer pain for patients with metastatic bone tumors with controllable related complications.