Estimation of the tumor size at cure threshold among adult patients with adrenocortical carcinoma: A populational-based study.

Background: The prognostic significance of tumor size with adrenocortical carcinoma (ACC) patients has not yet been thoroughly evaluated. Our objective was to investigate the influence of tumor size on prognostic value in adult ACC patients. Methods: The Surveillance, Epidemiology and End Results Program (SEER) was employed to identify adult ACC patients who had been diagnosed from 2004 to 2015. The "X-Tile" program determined the optimal cutoff value of tumor size. Cancer-specific survival (CSS) and overall survive (OS) were estimated. The survival outcomes and risk factors were analyzed by the Kaplan-Meier methods and the multivariable cox regression respectively. Results: A total 426 adult ACC patients were included. Univariable and multivariable cox analysis revealed age, larger tumor size and metastasis as consistent predictors of lower CSS and OS. The optimal cutoff value of tumor size was identified as 8.5 cm using X-tile software, and Kaplan-Meier method showed dramatic prognostic difference between patients with larger tumors (＞8.5 cm) and smaller tumors (≤8.5 cm) (log-rank test, P < 0.001). Subgroup analyses revealed no statistical significance and a consistent proportionate effect of tumor size on CSS and OS across all eight pre-specified subgroups. Interestingly, an additional subgroup analysis showed that ACC patients could not benefit from chemotherapy in terms of CSS and OS. Conclusion: The study suggests that tumor size is a crucial prognostic factor in ACC patients and a cutoff value 8.5 cm might indicate a poor outcome. Given the limitations of the available data, it is challenging to conclusively determine the benefit of chemotherapy in adult ACC patients across different tumor size ranges.

A bibliometric insight into neoadjuvant chemotherapy in bladder cancer: trends, collaborations, and future avenues.

Background: Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) remains the cornerstone of treatment for muscle-invasive bladder cancer (MIBC). While platinum-based regimens have demonstrated benefits in tumor downstaging and improved long-term survival for selected patients, they may pose risks for those who are ineligible or unresponsive to chemotherapy. Objective: We undertook a bibliometric analysis to elucidate the breadth of literature on NAC in bladder cancer, discern research trajectories, and underscore emerging avenues of investigation. Methods: A systematic search of the Web of Science Core Collection (WoSCC) was conducted to identify articles pertaining to NAC in bladder cancer from 1999 to 2022. Advanced bibliometric tools, such as VOSviewer, CiteSpace, and SCImago Graphica, facilitated the examination and depicted the publication trends, geographic contributions, institutional affiliations, journal prominence, author collaborations, and salient keywords, emphasizing the top 25 citation bursts. Results: Our analysis included 1836 publications spanning 1999 to 2022, indicating a growing trend in both annual publications and citations related to NAC in bladder cancer. The United States emerged as the predominant contributor in terms of publications, citations, and international collaborations. The University of Texas was the leading institution in publication output. "Urologic Oncology Seminars and Original Investigations" was the primary publishing journal, while "European Urology" boasted the highest impact factor. Shariat, Shahrokh F., and Grossman, H.B., were identified as the most prolific and co-cited authors, respectively. Keyword analysis revealed both frequency of occurrence and citation bursts, highlighting areas of concentrated study. Notably, the integration of immunochemotherapy is projected to experience substantial growth in forthcoming research. Conclusions: Our bibliometric assessment provides a panoramic view of the research milieu surrounding neoadjuvant chemotherapy for bladder cancer, encapsulating the present state, evolving trends, and potential future directions, with a particular emphasis on the promise of immunochemotherapy.

Risk factor analysis of conversion in laparoscopic liver resection for intrahepatic cholangiocarcinoma.

BACKGROUND: The risk factors of patients with intrahepatic cholangiocarcinoma (ICC) requiring conversion to open surgery have not been adequately studied. This study aimed to determine the risk factors and postoperative outcomes of conversion in patients with ICC. METHODS: From May 2014 to September 2022, Unplanned conversions were compared with successful LLRs. RESULTS: 153 patients with ICC initially underwent LLR, of which 41 (26.8%) required conversion to open surgery. Multivariate analysis for those factors that were statistically significant or confirmed by clinical studies, tumor proximity to the major vessels (OR 6.643, P < 0.001), and previous upper abdominal surgery (OR 3.140, P = 0.040) were independent predictors of unplanned conversions. Compared to successful LLRs, unplanned conversions showed longer operative times (300.0 vs. 225.0 min, P < 0.001), more blood loss (500.0 vs. 200.0 mL, P < 0.001), higher transfusion rates (46.3% vs. 11.6%, P < 0.001), longer length of stays (13.0 vs. 8.0 days, P < 0.001), and higher rates of major morbidity (39.0% vs. 11.6%, P < 0.001). However, there was no statistically significant difference in 30-day or 90-day mortality between the conversion group and the laparoscopic group. CONCLUSION: Conversion during LLR should be anticipated in ICC patients with prior upper abdominal surgery or tumor proximity to major vessels as features.

Activation of IGFBP4 via unconventional mechanism of miRNA attenuates metastasis of intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy. Although its incidence is lower than that of hepatocellular carcinoma (HCC), ICC has a worse prognosis, and it is more prone to recur and metastasize, resulting in a far greater level of malignancy. METHODS: Bioinformatics analysis and qRT-PCR were applied to assess the level of miR-122-5p and IGFBP4. Western blot, transwell assays, wound-healing assays, real-time cellular invasion monitoring, in vivo study were applied to explore the function of miR-122-5p and IGFBP4. Dual luciferase reporter assays and chromatin isolation by RNA purification (ChiRP) were applied to explore the regulation of IGFBP4 by miR-122-5p. RESULTS: Using The Cancer Genome Atlas (TCGA) data set, Sir Run Run Shaw hospital data set and bioinformatics analyses, we identified miR-122-5p as a potential tumor suppressor in ICC and validated its suppressive effect in metastasis and invasion of ICC. Transcriptome sequencing, rescue and complement experiments were used to identify insulin-like growth factor binding protein 4 (IGFBP4) as a target of miR-122-5p. The mechanism by which miR-122-5p regulates IGFBP4 was clarified by chromatin separation RNA purification technology, and dual-luciferase reporter assays. We discovered a rare novel mechanism by which miR-122-5p promotes IGFBP4 mRNA transcription by binding to its promoter region. Furthermore, in mouse orthotopic metastasis model, miR-122-5p inhibited the invasion of ICC. CONCLUSION: In summary, our study revealed a novel mechanism of miR-122-5p and function of the miR-122-5p/IGFBP4 axis in the metastasis of ICC. We also highlighted the clinical value of miR-122-5p and IGFBP4 in inhibiting ICC invasion and metastasis.

Exploration of a screening model for intrahepatic cholangiocarcinoma patients prone to cuproptosis and mechanisms of the susceptibility of CD274-knockdown intrahepatic cholangiocarcinoma cells to cuproptosis.

Intrahepatic cholangiocarcinoma (ICC) is a form of liver cancer with poor long-term survival rates that requires novel therapeutic methods. Our team's previous research found that ICC patients prone to cuproptosis possessed a more satisfactory long-term prognosis and a more sensitive response to copper carrier Elesclomol. Thus, we aimed to identify new diagnostic and treatment strategies for ICC patients prone to cuproptosis and further explore the associated intracellular and extracellular mechanisms of ICC cells prone to cuproptosis. We employed FU-ICC (n = 255) as the training dataset, and validated our findings using SRRSH-ICC (from our center, n = 65), GSE26566 (n = 104), E-MTAB-6389 (n = 78), and scRNA-seq (n = 14) datasets. Single sample gene set enrichment analysis and subsequent unsupervised cluster analysis was conducted on the training dataset for the pan-programmed cell death gene set (including apoptosis, autophagy, ferroptosis, pyroptosis, necroptosis, and cuproptosis) to define and screen ICC patients prone to cuproptosis. We constructed a nomogram model using weighted gene co-expression network analysis and machine learning algorithms to predict ICC patients prone to cuproptosis, then explored its clinical value with multi-center transcriptome profiling. Furthermore, we validated the hub genes with in vitro and animal experiments to define ICC cells prone to cuproptosis. Ultimately, bulk and single-cell transcriptome profiling were utilized to explore the immune microenvironment of ICC cells prone to cuproptosis. Our nomogram model could help predict ICC patients prone to cuproptosis and possessed excellent prediction efficiency and clinical significance via internal and external verification. In vitro experiments demonstrated that ICC cells with siRNA-mediated knockdown of CD274 (PD-L1) and stimulation with elescomol-CuCl2 were prone to cuproptosis, and CD274-negative ICC cells could be defined as ICC cells prone to cuproptosis. The safety and feasibility of lenti-sh CD274+Elesclomol-CuCl2 as a therapeutic approach for ICC were verified using bioinformatics analysis and animal experiments. Bulk and single-cell transcriptome profiling indicated that the interactions between ICC cells prone to cuproptosis and monocytes/macrophages were particularly relevant. In conclusion, this study systematically and comprehensively explored cuproptosis in ICC for the first time. We constructed precise diagnostic and treatment strategies for ICC patients prone to cuproptosis and further explored the intracellular and extracellular mechanisms of ICC cells prone to cuproptosis. Further work with large prospective cohorts will help verify these conclusions.

Circ-RAPGEF5 promotes intrahepatic cholangiocarcinoma progression by stabilizing SAE1 to facilitate SUMOylation.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with a poor prognosis. The underlying functions and mechanisms of circular RNA and SUMOylation in the development of ICC remain poorly understood. METHODS: Circular RNA hsa_circ_0001681 (termed Circ-RAPGEF5 hereafter) was identified by circular RNA sequencing from 19 pairs of ICC and adjacent tissue samples. The biological function of Circ-RAPGEF5 in tumor proliferation and metastasis was examined by a series of in vitro assays. A preclinical model was used to validate the therapeutic effect of targeting Circ-RAPGEF5. RNA pull-down and dual-luciferase reporter assays were used to access the RNA interactions. Western blot and Co-IP assays were used to detect SUMOylation levels. RESULTS: Circ-RAPGEF5, which is generated from exons 2 to 6 of the host gene RAPGEF5, was upregulated in ICC. In vitro and in vivo assays showed that Circ-RAPGEF5 promoted ICC tumor proliferation and metastasis, and inhibited apoptosis. Additionally, high Circ-RAPGEF5 expression was significantly correlated with a poor prognosis. Further investigation showed that SAE1, a potential target of Circ-RAPGEF5, was also associated with poor oncological outcomes. RNA pull-down and dual-luciferase reporter assays showed an interaction of miR-3185 with Circ-RAPGEF5 and SAE1. Co-IP and western blot assays showed that Circ-RAPGEF5 is capable of regulating SUMOylation. CONCLUSION: Circ-RAPGEF5 promotes ICC tumor progression and SUMOylation by acting as a sponge for miR-3185 to stabilize SAE1. Targeting Circ-RAPGEF5 or SAE1 might be a novel diagnostic and therapeutic strategy in ICC.

Bulk and single-cell transcriptome profiling reveal extracellular matrix mechanical regulation of lipid metabolism reprograming through YAP/TEAD4/ACADL axis in hepatocellular carcinoma.

Emerging studies have revealed matrix stiffness promotes hepatocellular carcinoma (HCC) development. We studied metabolic dysregulation in HCC using the TCGA-LIHC database (n=374) and GEO datasets (GSE14520). HCC samples were classified into three heterogeneous metabolic pathway subtypes with different metabolic profiles: Cluster 1, an ECM-producing subtype with upregulated glycan metabolism; Cluster 2, a hybrid subtype with partial pathway dysregulation. Cluster 3, a lipogenic subtype with upregulated lipid metabolism; These three subtypes have different prognosis, clinical features and genomic alterations. We identified key enzymes that respond to matrix stiffness and regulate lipid metabolism through bioinformatic analysis. We found long-chain acyl-CoA dehydrogenase (ACADL) is a mechanoreactive enzyme that reprograms HCC cell lipid metabolism in response to extracellular matrix stiffness. ACADL is also regarded as tumor suppressor in HCC. We found that increased extracellular matrix stiffness led to activation of Yes-associated protein (YAP) and the YAP/TEA Domain transcription factor 4 (TEAD4) transcriptional complex was able to directly repress ACADL at the transcriptional level. The ACADL-dependent mechanoresponsive pathway is a potential therapeutic target for HCC treatment.

Inflammatory bowel disease is causally related to irritable bowel syndrome: a bidirectional two-sample Mendelian randomization study.

Introduction: Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are lifelong digestive diseases that severely impact patients' quality of life. The existence of a causal association between IBS and IBD remains unclear. This study aimed to determine the direction of causality between IBD and IBS by quantifying their genome-wide genetic associations and performing bidirectional two-sample Mendelian randomization (MR) analyses. Methods: Genome-wide association studies (GWAS) among a predominantly European patient cohort identified independent genetic variants associated with IBS and IBD. Two separate databases (a large GWAS meta-analysis and the FinnGen cohort) for both IBS and IBD were consulted to retrieve statistics on instrument-outcome associations. MR analyses included inverse-variance-weighted, weighted-median, MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods, and sensitivity analyses were performed. The MR analyses were carried out for each outcome data, followed by a fixed-effect meta-analysis. Results: Genetically predicted IBD was associated with an increased risk of IBS. Odds ratios (95% confidence intervals) for samples of 211,551 (17,302 individuals with IBD), 192,789 (7,476 Crohn's disease cases), and 201,143 (10,293 ulcerative colitis cases) individuals were 1.20 (1.00, 1.04), 1.02 (1.01, 1.03), and 1.01 (0.99, 1.03), respectively. After outlier correction using MR-PRESSO, the odds ratio for ulcerative colitis was 1.03 (1.02, 1.05) (p = 0.001). However, an association between genetically influenced IBS and IBD was not identified. Discussion: This study confirms that IBD is causally related to IBS, which may interfere with the diagnosis and treatment of both diseases.

Safety and feasibility of laparoscopic liver resection for intrahepatic cholangiocarcinoma: a propensity score-matched study.

BACKGROUND: Laparoscopic liver resection (LLR) is controversial in treating intrahepatic cholangiocarcinoma (ICC). Therefore, this study aimed to evaluate the safety and feasibility of LLR for the treatment of ICC and explored the independent factors affecting the long-term prognosis of ICC. METHODS: We included 170 patients undergoing hepatectomy for ICC from December 2010 to December 2021 and divided them into LLR group and open liver resection (OLR) group. We used propensity score matching (PSM) analysis to reduce the impact of data bias and confounding variables and then compared the short-term and long-term prognosis of LLR and OLR in treating ICC; Cox proportional hazards regression model was adopted to explore the independent factors affecting the long-term prognosis of ICC. RESULTS: A total of 105 patients (70 in the LLR group and 35 in the OLR group) were included after 2:1 PSM analysis. There was no difference in demographic characteristics and preoperative indexes between the two groups. The perioperative results of the OLR group were worse than those of the LLR group, that is, the intraoperative blood transfusion rate (24 (68.6) vs 21 (30.0)), blood loss (500 (200-1500) vs 200 (100-525)), and the morbidity of major postoperative complications (9 (25.7) vs 6 (8.5)) in the OLR group were worse than those in LLR group. LLR could enable patients to obtain an equivalent long-term prognosis compared to OLR. The Cox proportional hazards regression model exhibited that no matter before or after PSM, preoperative serum CA12-5 and postoperative hospital stay were independent factors affecting overall survival, while only lymph node metastasis independently influenced recurrence-free survival. CONCLUSIONS: Compared with ICC treated by OLR, the LLR group obtained superior perioperative period outcomes. In the long run, LLR could enable ICC patients to receive an equivalent long-term prognosis compared to OLR. In addition, ICC patients with preoperative abnormal CA12-5, lymph node metastasis, and more extended postoperative hospital stay might suffer from a worse long-term prognosis. However, these conclusions still need multicenter extensive sample prospective research to demonstrate.

The global research of bladder cancer immunotherapy from 2012 to 2021: A bibliometric analysis.

Intravesical instillation of Bacillus Calmette-Guérin has been used as an immunotherapy to treat superficial bladder cancer for almost half a century. In recent years, the approval of several monoclonal antibody treatments has transformed the treatment landscape for patients with muscle-invasive or metastatic uroepithelial carcinoma. The purpose of this study was to conduct a thorough review of immunotherapy in bladder cancer through a bibliometric approach. Publications related to bladder cancer immunotherapy were obtained from the Web of Science Core Collection on July 1st, 2022. We conducted a bibliometric analysis of literature information using CiteSpace IV, VOSviewer, and Scimago Graphica, including co-authorship or co-citation of authors, countries/regions, journals, references, and keyword co-occurrence. There was a total of 2,352 papers included, with the most contributions coming from the United States, China, and Italy. The United States had the highest H-index value and was the leading country in this field. Meanwhile, the number of publications in China was steadily growing. The top three productive researchers were Kamat AM, Necchi A, and Shariat SF, with Powles T as the top co-cited author. Most papers were published by the University of Texas System. The majority of papers in this field were published in Urologic Oncology Seminars and Original Investigations and European Urology was the most influential journal with the highest H-index. The tumor microenvironment and complete molecular characterization may still be the frontier in this research area, allowing us to obtain a better understanding of the pathogenesis and clinical prognosis of bladder cancer. More research are conducted to identify clinically meaningful biomarkers that may provide opportunities for the personalization of bladder cancer therapy. This study provides clinicians and researchers with an overview and helpful guidance on how to choose the research direction and management of bladder cancer immunotherapy.

Knowledge mapping and current trends of immunotherapy for prostate cancer: A bibliometric study.

Background: Prostate cancer (PCa) is the second most common malignancy in men worldwide. Growing evidence substantiates the important role of immunotherapy in human tumors. Given that immunotherapy is often unsatisfactory on PCa, many studies have been conducted on PCa immunotherapy to improve treatment efficacy. However, no relevant bibliometric study of PCa immunotherapy has hitherto been reported. A bibliometric analysis was performed to evaluate the global scientific production of PCa immunotherapy research and characterize the development trends for future studies in this article. Methods: The publications related to PCa immunotherapy were extracted from the Web of Science Core Collection. The contribution and co-occurrence relationships of countries/regions, institutions, journals, references, authors, and keywords were assessed and visualized by VOSviewer and CiteSpace to identify research hotspots and potential future trends. Results: A total of 3,583 publications related to PCa immunotherapy from 1999 to 2021 were collected. The results of annual publications and citations exhibited a steady increase over the past 22 years. The National Cancer Institute in the USA published far more papers during the study than any institute. Accordingly, the USA had the most publications (n = 1,954, 54.54%). Gulley, James L. had the most number of published papers, and Small, Eric J. was the most co-cited authors in this field. Cancer Immunology Immunotherapy was the most productive journal, with 145 publications on PCa immunotherapy. Keyword cluster and keyword burst analyses showed that research in PCa immunotherapy shifted from "t cell infiltration" and "sipuleucel t" to "immune checkpoint inhibitor", "CTLA-4", and "PD-L1 expression". Conclusion: PCa immunotherapy has attracted much attention, reflected by the increasing number of annual publications and citations. Much emphasis has been placed on exploring the complex immunogenicity and tumor microenvironment for PCa and identifying the patient population who can benefit from immunotherapy. Combining immune checkpoint inhibitors with other therapeutic options and cancer vaccines represents the future development trends in PCa immunotherapy.

Bibliometric analysis of the global research development of bone metastases in prostate cancer: A 22-year study.

Background: Prostate cancer (PCa) is the second most diagnosed cancer in men. Most PCa-related deaths result from metastatic disease. Metastases occur most often in the bones (90%). However, the current treatments for bone metastases in PCa are not very effective. Here we present an overview of the current research situation of bone metastases in PCa, focusing on hotspots and trends. Methods: We searched the Web of Science Core Collection database for publications related to bone metastases in PCa published between 1999 and 2021. We used VOSviewer, CiteSpace, and a bibliometric online platform to perform a bibliometric analysis of countries, institutions, authors, journals, references, and keywords. Results: A total of 4,832 related articles were included in the present study. The USA published the most articles in the field, followed by China and England. The University of Texas MD Anderson Cancer Center is the leading institution in the research field of bone metastases in PCa. Saad F, from Canada, has made great achievements in this area by publishing 91 related articles. Prostate is the journal which published most related articles, and Mundy GR, 2002, Nat Rev Cancer, is the most cited article in this field. Furthermore, the analysis of author keywords can be divided into five clusters: (1) diagnosis of PCa, (2) mechanism of bone metastasis, (3) drug treatments of bone metastases, (4) radiotherapy of bone metastases, and (5) treatments and prognosis of PCa. Conclusions: mCRPC has been the hottest topic in PCa in recent years. CT is the most common diagnostic method for bone metastases. Enzalutamide and radium-223, as important treatments for bone metastases in PCa, bring about widespread attention. Furthermore, the researchers focus on the tumor microenvironment and biomarkers to explore the mechanism and the therapeutic targets of bone metastases in PCa.

m6A methylation regulators as predictors for treatment of advanced urothelial carcinoma with anti-PDL1 agent.

Purpose: Immune checkpoint blockade agents were shown to provide a survival advantage in urothelial carcinoma, while some patients got minimal benefit or side effects. Therefore, we aimed to investigate the prognostic value of m6A methylation regulators, and developed a nomogram for predicting the response to atezolizumab in urothelial carcinoma patients. Methods: A total of 298 advanced urothelial carcinoma patients with response data in the IMvigor210 cohort were included. Differential expressions of 23 m6A methylation regulators in different treatment outcomes were conducted. Subsequently, a gene signature was developed in the training set using the least absolute shrinkage and selection operator (LASSO) regression. Based on the multivariable logistic regression, a nomogram was constructed by incorporating the gene signature and independent clinicopathological predictors. The performance of the nomogram was assessed by its discrimination, calibration, and clinical utility with internal validation. Results: Six m6A methylation regulators, including IGF2BP1, IGF2BP3, YTHDF2, HNRNPA2B1, FMR1, and FTO, were significantly differentially expressed between the responders and non-responders. These six regulators were also significantly correlated with the treatment outcomes. Based on the LASSO regression analysis, the gene signature consisting of two selected m6A methylation regulators (FMR1 and HNRNPA2B1) was constructed and showed favorable discrimination. The nomogram integrating the gene signature, TMB, and PD-L1 expression on immune cells, showed favorable calibration and discrimination in the training set (AUC 0.768), which was confirmed in the validation set (AUC 0.755). Decision curve analysis confirmed the potential clinical usefulness of the nomogram. Conclusions: This study confirmed the prognostic value of FMR1 and HNRNPA2B1, and constructed a nomogram for individualized prediction of the response to atezolizumab in patients with urothelial carcinoma, which may aid in making treatment strategies.

Global research trends and foci of artificial intelligence-based tumor pathology: a scientometric study.

BACKGROUND: With the development of digital pathology and the renewal of deep learning algorithm, artificial intelligence (AI) is widely applied in tumor pathology. Previous researches have demonstrated that AI-based tumor pathology may help to solve the challenges faced by traditional pathology. This technology has attracted the attention of scholars in many fields and a large amount of articles have been published. This study mainly summarizes the knowledge structure of AI-based tumor pathology through bibliometric analysis, and discusses the potential research trends and foci. METHODS: Publications related to AI-based tumor pathology from 1999 to 2021 were selected from Web of Science Core Collection. VOSviewer and Citespace were mainly used to perform and visualize co-authorship, co-citation, and co-occurrence analysis of countries, institutions, authors, references and keywords in this field. RESULTS: A total of 2753 papers were included. The papers on AI-based tumor pathology research had been continuously increased since 1999. The United States made the largest contribution in this field, in terms of publications (1138, 41.34%), H-index (85) and total citations (35,539 times). We identified the most productive institution and author were Harvard Medical School and Madabhushi Anant, while Jemal Ahmedin was the most co-cited author. Scientific Reports was the most prominent journal and after analysis, Lecture Notes in Computer Science was the journal with highest total link strength. According to the result of references and keywords analysis, "breast cancer histopathology" "convolutional neural network" and "histopathological image" were identified as the major future research foci. CONCLUSIONS: AI-based tumor pathology is in the stage of vigorous development and has a bright prospect. International transboundary cooperation among countries and institutions should be strengthened in the future. It is foreseeable that more research foci will be lied in the interpretability of deep learning-based model and the development of multi-modal fusion model.

Emerging trends and research foci of oncolytic virotherapy for central nervous system tumors: A bibliometric study.

Background: Central nervous system tumor (CNST) is one of the most complicated and lethal forms of human tumors with very limited treatment options. In recent years, growing evidence indicates that oncolytic virotherapy (OVT) has emerged as a promising therapeutic strategy for CNSTs. And a considerable amount of literature on OVT-CNSTs has been published. However, there are still no studies summarizing the global research trends and hotspots of this field through a bibliometric approach. To fulfill this knowledge gap, bibliometric analysis was conducted based on all publications relating to OVT-CNSTs since 2000s. Methods: We searched the Web of Science Core Collection for all relevant studies published between 2000 and 2022. Four different tools (online analysis platform, R-bibliometrix, CiteSpace and VOSviewer) were used to perform bibliometric analysis and network visualization, including annual publication output, active journals, contribution of countries, institutions, and authors, references, as well as keywords. Results: A total of 473 articles and reviews were included. The annual number of publications on OVT-CNSTs showed a significant increasing trend. Molecular Therapy and Cancer Research were the most active and co-cited journals, respectively. In terms of contributions, there is no doubt that the United States occupied a leading position with the most publications (n=307, 64.9%) and the highest H-index (57). The institution and author that contributed the largest number of publications were Ohio State University and Chiocca EA, respectively. As can be seen from citation analysis, the current studies mainly focused on preclinical and phase I/II clinical results of various oncolytic virus for CNSTs treatment. Keywords co-occurrence and burst analysis revealed that the following research topics including immunotherapy, T-cells, tumor microenvironment, vaccine, blood-brain-barrier, checkpoint inhibitors, macrophage, stem cell, and recurrent glioblastoma have been research frontiers of this field and also have great potential to continue to be research hotspots in the future. Conclusion: There has been increasing attention on oncolytic viruses for use as CNSTs therapeutics. Oncolytic immunotherapy is a topic of great concern in this field. This bibliometric study provides a comprehensive analysis of the knowledge base, research hotspots, development perspective in the field of OVT-CNSTs, which could become an essential reference for scholars in this area.

Knowledge mapping and research hotspots of immunotherapy in renal cell carcinoma: A text-mining study from 2002 to 2021.

Background: Renal cell carcinoma (RCC) is one of the most lethal urological malignancies, and because early-stage RCC is asymptomatic, many patients present metastatic diseases at first diagnosis. With the development of immunotherapy, the treatment of RCC has entered a new stage and has made a series of progress. This study mainly outlines the knowledge map and detects the potential research hotspots by using bibliometric analysis. Methods: Publications concerning RCC immunotherapy from 2002 to 2021 in the Web of Science Core Collection were collected. Visualization and statistical analysis were mainly performed by freeware tools VOSviewer, CiteSpace, R software, and Microsoft Office Excel 2019. Results: A total of 3,432 papers were collected in this study, and the annual number of papers and citations showed a steady growth trend. The United States is the leading country with the most high-quality publications and is also the country with the most international cooperation. The University of Texas MD Anderson Cancer Center is the most productive organization. The Journal of Clinical Oncology is the highest co-cited journal, and Brian I. Rini is both the most prolific author and the author with the largest centrality. The current research hotspots may be focused on "immune checkpoint inhibitors (ICIs)," "PD-1," and "mammalian target of rapamycin." Conclusion: Immunotherapy has a bright future in the field of RCC treatment, among which ICIs are one of the most important research hotspots. The main future research directions of ICI-based immunotherapy may focus on combination therapy, ICI monotherapy, and the development of new predictive biomarkers.

Frontiers of ferroptosis research: An analysis from the top 100 most influential articles in the field.

In recent years, ferroptosis has become a research hotspot in programmed cell death. Since the concept of ferroptosis was proposed, a growing number of articles have been published on this topic. Nevertheless, to our knowledge, these ferroptosis-related publications that have received a great deal of attention have not been quantitatively evaluated. In this study, we analyzed the top 100 most influential articles over the past decade through a bibliometric method to characterize the research status and trends in this field. Web of Science Core Collection was searched to identify relevant studies. After being manually screened, the top 100 most cited studies with original data were identified and analyzed. Bibliometric software including VOSviewer and R-Bibliometrix were used to perform visualization analysis. The citation frequency for the top 100 selected articles ranged from 135 to 3603 (326.6 citations on average). These articles originated from 25 countries/regions, with more than half originating from the United States and China. The most frequently nominated author was Stockwell BR from the Columbia University, and of the top 100 articles, 19 listed his name. Three core journals were Nature, Cell and Proceedings of the National Academy of Sciences of the United States of America. In addition to term of ferroptosis, these terms or phrases including cell death, cancer cell, GPX4, pathway, inhibitor, mechanism, iron, lipid peroxidation, resistance, erastin, sorafenib, P53, reactive oxygen species, necroptosis, apoptosis, glutathione peroxidase, ACSL4, autophagy, and SLC7A11 appeared more frequently in the top 100 articles. Overall, although much progress has been made, the research on ferroptosis is still at an early stage. The current attention in this field mainly focuses on potential regulatory mechanism and pathways including key ferroptosis-related genes/molecules, oxidant and antioxidant system, ferroptosis-inducing agents or nanomedicine for cancer therapy, as well as the role of ferroptosis in non-neoplastic disorders. Meanwhile, combination therapeutic strategies targeting ferroptosis in radiotherapy or immunotherapy also deserve further attention.