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Abstract Background This network meta-analysis aimed to assess the comparative efficacy and safety of combinations involving three cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and endocrine therapies (ETs) in patients with metastatic or advanced breast cancer (BC) who are hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-). Methods We initially identified relevant studies from previous meta-analyses and then conducted a comprehensive search of PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases to locate additional studies published between February 2020 and September 2021. Essential data were extracted, and a network meta-analysis was performed using R 4.1.1 software with a random-effects model. Furthermore, we assigned rankings to all available treatment combinations by calculating their cumulative probability. Results Data analysis included ten reports from nine studies. Pooled results demonstrated that each treatment combination significantly reduced the hazard risk of progression-free survival (PFS) compared to treatment with an aromatase inhibitor (AI) or fulvestrant alone. However, there were no differences observed in PFS or overall survival (OS) among the different treatment combinations. Additionally, patients receiving palbociclib plus AI and abemaciclib plus AI or fulvestrant experienced more severe adverse events (AEs), with hazard ratios (HRs) of 10.83 (95% confidence interval [CI] = 2.3 to 52.51) and 4.8 (95%CI = 1.41 to 16.21), respectively. The HR for ribociclib plus AI was 9.45 (95%CI = 2.02 to 43.61), and the HR for palbociclib plus fulvestrant was 6.33 (95%CI = 1.03 to 39.86). Based on the ranking probabilities, palbociclib plus fulvestrant had the highest probability of achieving superior PFS (37.65%), followed by abemaciclib plus fulvestrant (28.76%). For OS, ribociclib plus fulvestrant ranked first (34.11%), with abemaciclib plus fulvestrant in second place (25.75%). In terms of safety, palbociclib plus AI (53.98%) or fulvestrant (51.37%) had the highest probabilities of being associated with adverse events. Conclusions Abemaciclib plus fulvestrant or ribociclib plus AI appear to be effective and relatively safe for the treatment of HR+/HER2- metastatic or advanced BC patients. However, given the reliance on limited evidence, our findings require further validation through additional studies.

Breast cancer is the most frequent form of cancer in women and the primary cause of cancer-related deaths globally. DNA methylation and demethylation are important processes in human tumorigenesis. Ten-eleven translocation 3 (TET3) is a DNA demethylase. Prior research has demonstrated that TET3 is highly expressed in various human malignant tumors. However, the exact function and mechanism of TET3 in breast cancer remain unclear. In this study, we investigated TET3 expression in breast cancer and its correlation with clinicopathological characteristics of breast cancer patients. The results presented that TET3 expression was significantly increased in breast cancer and associated with the PAM50 subtype. Subsequently, we performed receiver operating characteristic, survival, and Cox hazard regression analyses. These results suggest that TET3 expression is associated with a poor prognosis and may be an indirect independent prognostic indicator in breast cancer. We also established a protein-protein interaction (PPI) network of TET3 and executed enrichment analyses of TET3 co-expressed genes, revealing their primary association with the cell cycle. Moreover, we identified noncoding RNAs (ncRNAs) contributing to TET3 overexpression using expression, correlation, and survival analyses. We identified the LINC01521/hsa-miR-29a-3p axis as the primary TET3 upstream ncRNA-related pathway in breast cancer. Furthermore, TET3 expression was positively associated with immune cell infiltration, immune cell biomarkers, and eight immune checkpoint gene expressions in breast cancer. TET3 expression also correlated with patient responses to immunotherapy. Finally, we conducted subcellular localization and immunohistochemical staining analysis of TET3 in breast cancer. We found that TET3 localized to the nucleoplasm, vesicles, and cytosol in the MCF-7 cell line, and TET3 expression was significantly upregulated in breast cancer tissues compared to para-tumor tissues. Our findings indicate that ncRNA-mediated overexpression of TET3 predicts an unfavorable prognosis and correlates with immunotherapy efficacy in breast cancer.

Abstract Background Management of acute postoperative pain is one of the major challenges in pediatric patients. Oral oxycodone has shown good pain relief in postoperative pain relief in children, but no studies have investigated intravenous oxycodone in this context. Objective whether oxycodone PCIA can provide adequate and safe postoperative pain relief, in comparison to tramadol as reference opioid drug. Design a randomized, double-blind, parallel, multi-center clinical trial. Setting five university medical centers and three teaching hospitals in China. Participants patients aged 3-month-old to 6-year-old undergoing elective surgery under general anesthesia. Intervention patients were randomly allocated to either tramadol (n = 109) or oxycodone (n = 89) as main postoperative opioid analgesic. Tramadol or oxycodone were administered with a loading dose at the end of surgery (1 or 0.1 mg.kg–1, respectively), then with a parent-controlled intravenous device with fixed bolus doses only (0.5 or 0.05 mg.kg–1, respectively), and a 10-min lockout time. Outcomes the primary outcome was adequate postoperative pain relief, defined as a face, legs, activity, cry, and consolability (FLACC) score

IntroductionBreast cancer remains a significant global health challenge, accounting for 2.3 million new cases in 2020 and ranking as the most prevalent cancer by incidence and the fourth in cancer-related mortality worldwide. In China, breast cancer also rapidly increases incidence and burden. The research of exosomes in breast cancer has attracted more and more attention and has a rapid development. Recognizing the pivotal role of exosomes in breast cancer research, we have undertaken a comprehensive scientometric analysis of pertinent scholarly articles published over the past decade to elucidate the current research landscape for researchers.MethodsIn this study, we gathered all pertinent publications from the Web of Science. Biblioshiny (a web interface for Bibliometrix), VOSviewer software, and CiteSpace software were used to analyze the information on publications, including global trends, countries, institutions, journals, authors, keywords, and citations.ResultsA total of 1,239 articles and 625 review articles were retrieved. The annual global publication output has an increased trend in recent decades overall. China contributed the most articles. The publications of the USA had the most total link strength. Nanjing Medical University had the most total link strength. The most relevant source was the International Journal of Molecular Sciences. Tang JH contributed the most articles and had the highest H-index, G-index, and total link strength. The most cited document was “Tumor exosome integrins determine organotropic metastasis”, with 2730 citations. The basic themes included “exosomes”, “expression”, “cells”, “identification”, “biomarkers”, and “serum”. The keyword “membrane vesicle” had the strongest bursts. The keywords “target”, “biology”, “suppressor cell”, “molecular mechanism”, “tumor progression”, “inhibitor”, and “model” appeared as prominent focal points in current research and active areas of exploration.ConclusionOver the past decade, exosome research in breast cancer has undergone a discernible evolution, shifting from broader investigations of exosome roles to focused exploration of specific pathways relevant to breast cancer. Notably, the emphasis has extended to the clinical application of exosomes as biomarkers and potential therapeutic agents in breast cancer treatment.

Over the past decade, thousands of articles have been published on the mechanistic target of rapamycin (mTOR) and its role in breast cancer. However, the variability and heterogeneity of academic data may impact the acquisition of published research information. Due to the large number, heterogeneity, and varying quality of publications related to mTOR and breast cancer, sorting out the present state of the research in this area is critical for both researchers and clinicians. Therefore, scientometric techniques and visualization tools were employed to analyze the large number of bibliographic metadata related to the research area of mTOR and breast cancer. The features of relevant publications were searched from 2012 to 2022 to evaluate the present status of research and the evolution of research hotspots in this particular field. Web of Science was utilized to extract all relevant publications from 2012 to 2022. Subsequently, Biblioshiny and VOSviewer were utilized to obtain data on the most productive countries, authors, and institutions, annual publications and citations, the most influential journals and articles, and the most frequently occurring keywords. In total, 1,471 publications were retrieved, comprising 1,167 original articles and 304 reviews. There was a significant rise in publications between 2015 and 2018, followed by a sharp decline in 2019 and a rebound since then. The publication with the highest number of citations was a 2012 review authored by Baselga et al. The United States had the highest number of publications, citations and connections among all countries. Oncotarget had the highest number of published articles among all the journals, and José Baselga had the strongest links with other authors. Excluding the search topics, the most frequently used words were “expression” (n = 297), “growth” (n = 228), “activation” (n = 223), “pathway” (n = 205), and “apoptosis” (n = 195). mTOR is crucially involved in breast cancer pathogenesis, but its exact mechanism of action remains controversial and warrants further investigation. The scientometric analysis provides a distinct overview of the existing state of research and highlights the topical issues that deserve further exploration.

IntroductionRecently, endoscopic thyroidectomy has been developed and applied to thyroid surgery to achieve minimized neck scar formation and enhanced aesthetic outcomes. Our scientometric research in this paper offers a thorough overview of endoscopic thyroidectomy from 2013 to 2022.MethodsAll pertinent articles on endoscopic thyroidectomy were obtained from the Web of Science Core Collection Database. The data on the number of citations and publications, most prolific countries and institutions, significant authors and journals, top themes, and keywords were analyzed by Biblioshiny, CiteSpace, and VOSviewer.ResultsThere were 758 publications, all of that were found from 2013 to 2022. The output of the annual publication showed an upward trend. A series of cases report by Anuwong et al. published in 2016 received the most citations. The country with the most articles published articles was South Korea, and the two countries with the most collaboration were South Korea and the United States. The most productive journal was Surgical Endoscopy and Other Interventional Techniques. Dionigi G, Kim HY, and Anuwong A were the writers with the most articles published, the highest h- and g-indices, and the strongest link strength, respectively. The keywords “endoscopic thyroidectomy”, “surgical”, “thyroidectomy”, “robotic thyroidectomy”, “experience”, and others were most used.ConclusionThe innovative surgical technique, transoral endoscopic thyroidectomy vestibular approach (TOETVA), leaves no scars and produces optimal cosmetic results. However, the long-term oncologic results for thyroid cancer performed with this approach are still missing. This scientometric analysis can offer valuable insights into the present research standing and key focal points in this domain, enabling researchers to gain a precise understanding of the state-of-the-art research in this area.

Although vaccination is regarded as one of the most significant achievements of public health, there also exists the phenomenon of vaccination hesitancy which refers to delay in acceptance or refusal of vaccination despite availability of vaccination services. In this study, we conducted a bibliometric analysis to provide a comprehensive overview of vaccination hesitancy research from 2013 to 2022. All related publications were retrieved from the Web of Science Core Collection Database. Information on annual publications, countries, organizations, journals, authors, keywords, and documents was analyzed adopting the bibliometix R-package, VOSviewer, and CiteSpace software. A total of 4042 publications were enrolled. The annual publications increased slightly before 2020 but had an extremely dramatic increase from 2020 to 2022. The United States contributed the most articles and had the greatest collaboration with other countries and organizations. The London School of Hygiene & Tropical Medicine was the most active institution. Vaccine was the most cited and influential journal while Vaccines was the most productive journal. It was Dube E who was the most productive authors with the highest h-index. The most frequent keywords were “vaccine hesitancy,” “COVID-19,” “SARS-CoV2,” “immunization,” “attitudes,” and “willingness.” Vaccination hesitancy to some extent hinders the achievement of global public health. The influencing factors vary across time, space, and vaccines. The COVID-19 pandemic and the development of COVID-19 vaccines have made this issue the focus of interest. The complexity and specific contexts of influencing factors of vaccination hesitancy require further study and will potentially be the focus of future research direction.

IntroductionSince the mid-2000s, breast cancer incidence among women has slowly increased at about 0.5% per year. In the last three decades, Breast Cancer Susceptibility Gene (BRCA) has been proven to be the crucial gene in encouraging the incidence and development of breast cancer. However, scientometric analysis on BRCA-related breast cancer is in shortage. Thus, to have a clear understanding of the current status and catch up with the hotspots, a scientometric analysis was conducted on specific academic publications collected from the Web of Science (WoS).MethodsWe searched the Web of Science Core Collection (WoSCC) to procure associated articles as our dataset. Bibliometric, CiteSpace, VOSviewer, and HistCite software were then applied to conduct visual analyses of countries, institutions, journals, authors, landmark articles, and keywords in this research field.ResultsA total of 7,266 articles and 1,310 review articles published between 2013 to 2022 were retrieved eventually. The annual output steadily rose year by year and peaked in 2021. The USA led the way in the number of published works, total citations, and collaboration. Breast Cancer Research and Treatment was the most favoured journal in this research field. Narod SA from the University of Toronto produced the most publications. At last, the most prominent keywords were “breast cancer” (n=1,778), “women” (n=1,369), “brca1” (n=1,276), “ovarian cancer” (n=1,259), “risk” (n=1,181), and “mutations” (n=929), which exposed the hotspots within the BRCA domain of breast cancer study.ConclusionThe tendency in the BRCA research field over the past decade was presented by the scientometric analysis. The current research focus is the clinical trials of poly-adenosine diphosphate ribose polymerase inhibitors (PARPi) drugs and their resistance mechanisms.

Introduction: In recent years, more and more studies have proved that lipid metabolism plays an essential role in breast cancer’s proliferation and metastasisand also has a specific significance in predicting survival.Methods: This paper collected data from 725 publications related to lipid metabolism in breast neoplasm from 2012 to 2021 through the Web of Science Core Collection database. Bibliometrix, VOSviewer, and CiteSpace were used for the scientometrics analysis of countries, institutions, journals, authors, keywords, etc.Results: The number of documents published showed an increasing trend, with an average annual growth rate of 14.49%. The United States was the most productive country (n = 223, 30.76%). The journals with the largest number of publications are mostly from developed countries. Except for the retrieved topics, “lipid metabolism” (n = 272) and “breast cancer” (n = 175), the keywords that appeared most frequently were “expression” (n = 151), “fatty-acid synthase” (n = 78), “growth” (n = 72), “metabolism” (n = 67) and “cells“ (n = 66).Discussion: These findings and summaries help reveal the current research status and clarify the hot spots in this field.

IntroductionThe aims of this research were to conduct the first holistic and deep scientometric analysis of electronic waste and health and provide with the prediction of research trends and hot topics.MethodA comprehensive literature search was conducted via the Web of Science Core collection databases on 26 August 2022 to identify all articles related to electronic waste and health. A total of 652 records have been extracted from the Web of Science after applying inclusion and exclusion criteria and were analyzed using bibliometrix software of R-package, VOSviewer, and CiteSpace, visualized by tables and diagrams.ResultThe number of publications and total citations had shown a general growth trend from 2012 to 2021, with an average annual growth rate of 23.74%. Mainland China was the significant nation with the greatest number of publications, citations, and international links. The journal publishing the most was “Science of the Total Environment” (n = 56). Huo X and Hu XJ were the top two author contributing to this field with the highest h-index (23). Over time, the focus in this field shifted to exposure to heavy metal, polychlorinated biphenyls, polybrominated biphenyl ethers, and poly- and perfluorinated alkyl substances from electronic waste, and managements, such as hydrometallurgy.DiscussionBy this scientometric analysis, we found that the most active country, journal, organization and author contributing to this filed, as well as high impact documents and references and research hotspots. Also, we found that the hotspots might be exposure to toxic substances from electronic waste procession, its impact on human health and relevant managements. And evironmentally friendly materials to replace heavy metal mate rials, and environmentally friendly and effective recycling methods of electronic waste need to be further studied.

In recent years, anti-PD-1/anti-PD-L1 has been considered to be a valuable therapeutic target and prognostic indicator for triple-negative breast cancer. We analyzed all publications published in the field from their inception until the present day in order to determine the current research status and hotspots. All related publications were searched on the Web of Science. Our research used R-studio (bibliometrix package), VOSviewer, and CiteSpace to analyze and obtain annual publications and citation information, articles, highest publication countries and affiliations, influential journals and authors, keyword analysis, and keyword bursts. In total, 851 documents were retrieved including 628 articles and 223 review articles. The output of publications increased year by year from 2013 to 2021. However, the average article citation times reached the top in 2014 but generally showed a downward trend from 2014 to 2021. It was an article written by Schmid et al. in 2018 that received the most citations. With regard to publications, citations, and link strength, among the top countries was the United States. Cancers was the most published journal. Schmid and Loi ranked top in total citations and h-index. Schmid has the largest M-index and Loi has the most publication. The keywords that received the most attention were “Immunotherapy”, “PD-L1”, “Triple-negative breast cancer”, “Tumor-infiltrating lymphocytes”, and “Expression”. According to the report, this current research focuses on immunotherapy for triple-negative breast cancer and the expression of PD-L1 and tumor-infiltrating lymphocytes (TILs). Pembrolizumab and Atezolizumab plus chemotherapy have completed the Phase 3 clinical trial. However, the biomarkers were limited in predicting the treatment prognosis. Through the scientometric analysis, we can understand the current research status and potential research points in this filed and provide research direction for researchers.

BackgroundRecently, ctDNA has become the focus for scientists with respect to personalized treatment, early screening, precise diagnosis, and prognosis of BC. This paper aims to use bibliometric analysis to investigate the research status and future trends in this field.MethodsAll the related literature in the field of ctDNA and breast cancer was gathered from the Web of Science Core Collection. Data analyses were performed with R package Bibliometrics, VOS viewer 1.6.18, and online analysis in WoS. IBM SPSS (version 26.0) was used for statistical analysis.ResultsA total of 739 publications, including 472 articles and 267 reviews, were retrieved. The overall number of articles published showed an upward trend. The United States has the largest number of published articles (266 papers) and citations (20,225 times). The most productive journal was Clinical Cancer Research. Cristofanilli M was the most prolific author, while Carlos C was the most cited one. The most frequent keywords excluding the search subject were “liquid biopsy”, “plasma”, “mutations”, “metastatic breast cancer”, “acquired resistance”.ConclusionThis article explored the application value of ctDNA in breast cancer with bibliometric analysis, offering an overall and intuitive understanding of this topic and revealing the study trends in the past ten years.

Introduction:As one of the major pollutants in ambient air pollution, fine particulate matter (PM2.5) has attracted public attention. A large body of laboratory and epidemiological research has shown that PM2.5 exposure is harmful to human health.MethodsTo investigate its association with the commonly observed PM-related cancer, a bibliometric study was performed on related publications from 2012 to 2021 from a macroscopic perspective with the help of the Web of Science database and scientometric software VOSviewer, CiteSpace V, HistCite, and Biblioshiny.ResultsThe results indicated that of the 1,948 enrolled documents, scientific productions increased steadily and peaked in 2020 with 348 publications. The most prolific authors, journals, organizations, and countries were Raaschou-Nielsen O, Science of the Total Environment, the Chinese Academy of Sciences, and China, respectively. The top five keywords in frequency order were “air pollution,” “particulate matter,” “lung cancer,” “exposure,” and “mortality.”DiscussionThe toxic mechanism of carcinogenicity was explained and is worthy of further investigation. China and the US collaborated most closely, and it is hoped the two countries can strengthen their collaboration to combat air pollution. There is also a need to identify the components of PM2.5 and refine the models to assess the global burden of disease attributed to PM2.5 exposure.

IntroductionRecently, emerging contaminants have been discovered in the aquatic environment that can cause a range of human diseases, including cancer. In this study, our scientometric analysis provides a comprehensive overview of emerging contaminants and cancer research from 2012 to 2021.MethodsThe Web of Science Core Collection Database was used to retrieve all related publications. The bibliometix R-package, CiteSpace, and VOSviewer were applied to collect information on annual citations and publications, famous journals and authors, the most productive countries and organizations, popular topics, and keywords.ResultsA total of 2378 publications were retrieved. The publication's output showed a gradual upward trend from 2012 to 2021. The most-cited paper was a review article by Vandenberg et al. that was published in 2012. According to the analysis results, the United States published the most articles. The closest collaboration was between the United States and China. Environmental Research and Science of The Total Environment published the most paper. It was Choi KC who was the most productive and had the highest h-index, g-index, and m-index among the authors. The most frequently used keywords were “exposure,” “endocrine-disrupting chemicals,” “endocrine disruptors,” “cancer,” “bisphenol-a,” and so on.DiscussionEmerging contaminants play a significant role in cancer development. However, most studies are conducted in vivo with human cells or animal models, and relatively few are on human models. The scientometric analysis offers researchers a clear picture of the current state of research and hotspots in this field. From our study, researchers may find some hotspots that merit in-depth investigation.

Over the past 2 years, the world has witnessed the devastating effects of the COVID-19 pandemic on humanity. Fortunately, stem cell therapy is widely used in clinical practice for the treatment of COVID-19 and has saved the lives of many critically ill patients. A bibliometric analysis of this field can analyze research hotspots and predict the research trends. This research analyzed documents from Web of Science between the years 2020–2022. The bibliometrics software bibliometrix, VOSviewer, and CiteSpace were used to complete the visual analysis of publications, authors, countries, documents, organizations, collaborative networks, and keywords clustering. 896 publications on COVID-19 stem cell therapy were included in the analysis, including 451 articles and 445 review articles. The field grew at the average growth rate of 103.17% between 2020 and 2021. The United States had the highest number of publications and citations. Many developing countries had also contributed significantly to the field. The journal with the most articles was Stem Cell Research and Therapy. The most cited journal was Stem Cell Reviews and Reports. The published documents were focused on five themes: “Cell Biology”, “Medicine Research Experimental”, “Cell Tissue Engineering”, “Immunology”, and “Pharmacology Pharmacy”. The bibliometric analysis revealed that current clinical trials had validated stem cell therapy's remarkable potential in treating COVID-19 and its complications. It is foreseeable that future research in this area will continue to increase. With the help of bibliometric analysis, researchers can identify the current state of research and potential research hotspots.

BackgroundPoor immunogenicity and extensive immunosuppressive T-cell infiltration in the tumor immune microenvironment (TIME) have been identified as potential barriers to immunotherapy success in “immune-cold” breast cancers. Thus, it is crucial to identify biomarkers that can predict immunotherapy efficacy. Protein tyrosine phosphatase receptor type O (PTPRO) regulates multiple kinases and pathways and has been implied to play a regulatory role in immune cell infiltration in various cancers.MethodsESTIMATE and single-sample gene set enrichment analysis (ssGSEA) were performed to uncover the TIME landscape. The correlation analysis of PTPRO and immune infiltration was performed to characterize the immune features of PTPRO. Univariate and multivariate Cox analyses were applied to determine the prognostic value of various variables and construct the PTPRO-related CD8+ T-cell signatures (PTSs). The Kaplan–Meier curve and the receiver operating characteristic (ROC) curve were used to estimate the performance of PTS in assessing prognosis and immunotherapy response in multiple validation datasets.ResultsHigh PTPRO expression was related to high infiltration levels of CD8+ T cells, as well as macrophages, activated dendritic cells (aDCs), tumor-infiltrating lymphocytes (TILs), and Th1 cells. Given the critical role of CD8+ T cells in the TIME, we focused on the impact of PTPRO expression on CD8+ T-cell infiltration. The prognostic PTS was then constructed using the TCGA training dataset. Further analysis showed that the PTS exhibited favorable prognostic performance in multiple validation datasets. Of note, the PTS could accurately predict the response to immune checkpoint inhibitors (ICIs).ConclusionPTPRO significantly impacts CD8+ T-cell infiltration in breast cancer, suggesting a potential role of immunomodulation. PTPRO-based PTS provides a new immune cell paradigm for prognosis, which is valuable for immunotherapy decisions in cancer patients.

Breast cancer (BC), the most common malignancy in women, has a high cancer-related mortality. Endoplasmic reticulum stress (ERS), a response to the accumulation of unfolded proteins, has emerging roles in tumorigenesis, including invasion, metastasis, immune escape, etc. However, few studies have focused on the correlation between ERS with long non-coding RNAs (lncRNAs) in BC. We attempted to construct an ERS-related lncRNA prognostic signature and study its value in BC from tumor mutational burden (TMB), tumor immune microenvironment (TIME), cluster, clinical treatment, and so on. In the present study, transcriptomic and clinical data of BC patients were extracted from The Cancer Genome Atlas (TCGA) database. Correlation test, Cox regression analysis, least absolute shrinkage, and selection operator (LASSO) method were performed to determine an ERS-related lncRNA prognostic signature. Survival and predictive performance were analyzed according to Kaplan–Meier curves and receiver operating characteristic (ROC) curves, while nomograms and calibration curves were established. Then, an enrichment analysis was performed to study the functions and biological processes of ERS-related lncRNAs. TMB and TIME were also analyzed to assess the mutational status and immune status. Additionally, by using consensus cluster analysis, we compared differences among tumor subtypes. Drug sensitivity analysis and immunologic efficacy evaluations were performed together for further exploration. We identified a novel prognostic signature consisting of 9 ERS-related lncRNAs. High-risk patients had worse prognoses. The signature had a good predictive performance as an independent prognostic indicator and was significantly associated with clinicopathological characteristics. Enrichment analysis showed that metabolic pathways were enriched in high-risk patients, while immune pathways were more active in low-risk patients. Low-risk patients had lower TMB, higher immune scores, and stronger immune functions. Cluster analysis clarified that cluster 2 had the most active immune functions and was sensitive to more drugs, which may have the best clinical immunological efficacy. A clinical efficacy evaluation revealed that patients in the low-risk group may benefit more from chemotherapy, targeted therapy, and immunotherapy. The novel signature has significant clinical implications in prognosis prediction for BC. Our study clarifies that there is a potential connection between the ERS-related lncRNAs and BC, which may provide new treatment guidelines for BC.

Background and ObjectivePrevious studies determined the therapeutic effects of capecitabine-based chemotherapy regimens on early-stage triple-negative breast cancer (TNBC). However, the optimal strategy of capecitabine-based chemotherapy remains uncertain. We conducted this network meta-analysis to address this issue.MethodsWe systematically searched PubMed, Embase, and the Cochrane Registry of Controlled Trials (CENTRAL) to retrieve eligible studies published before September 2021. Two independent reviewers extracted information from eligible studies using a pre-designed data extraction sheet. The primary outcome included disease-free survival, and the second outcome showed overall survival and adverse events. Direct meta-analysis was performed using RevMan 5.4, and Bayesian network analysis was performed using R version 3.6.1 with the “gemtc” and “rjags” packages.ResultsNine studies involving 3661 TNBC patients met the selection criteria. The network meta-analysis suggested that the addition of capecitabine to adjuvant chemotherapy achieved a significantly longer disease-free (HR = 0.66, 95% CrI = 0.49 to 0.86) and overall survival time (HR = 0.60, 95% CrI = 0.43 to 0.83) than standard chemotherapy. All comparisons did not achieve statistical significance. The addition of capecitabine to adjuvant chemotherapy was the most effective treatment for improving disease-free (81.24%) and overall survival (78.46%) times, and the replacement of capecitabine to adjuvant chemotherapy was the safest regime.ConclusionsBased on available evidence, capecitabine-based chemotherapy benefits TNBC patients, and the addition of capecitabine with adjuvant chemotherapy was the most effective regime. In contrast, the replacement of capecitabine to adjuvant chemotherapy was the safest regime. More studies of high quality and large scale are needed to confirm our findings.

Recently, the androgen receptor has been found as a potential prognostic index and therapeutic target for breast cancer. To reveal the current research status and hotspots in this area, we analyzed the characteristics of related publications from 2011 to 2020. All related publications from 2011 to 2020 were retrieved from the Web of Science. Biblioshiny, VOSviewer, and CiteSpace V were applied to obtain the information on annual publications and citations, the highest yielding countries and authors, influential journals and articles, as well as hot keywords. In total, 2,118 documents, including 1,584 original articles and 534 reviews, were retrieved. Annual publication output was rich from 2014 to 2018, reaching the top in 2017. A systematic review written by Lehman et al. in 2011 was the most-cited document and reference. The United States was the leading country with the maximum number of publications, citations, and link strengths with other countries. The journal publishing the most was Oncotarget. Lehmann was the author who had the highest link strengths with other authors. The most highlighted keywords were “androgen receptor” (n = 1,209), “breast cancer” (n = 690), “expression” (n = 545), “breast cancer” (n = 410), “prostate cancer” (n = 290), and so on, revealing the trend from molecular mechanism level to therapeutic use level. The androgen receptor plays a significant role in the development of breast cancers, whereas its therapeutic value seems to be controversial and needs further study. With the help of a scientometric analysis in this field, researchers can clarify the current research status and hotspots worth fully exploring.

Thyroid cancer (THCA) is a common endocrine malignancy. With increasing incidence and low mortality, balancing the therapeutic approach is an inevitable issue. This study aimed to confirm the role of miR-222-3p and its target genes in THCA survival and immune infiltration. From different expression analyses based on the GEO and TCGA databases, we predicted and subsequently identified the key target genes of miR-222-3p. We then explored the expression, enrichment, pairwise correlation, protein expression, survival analysis, principal component analysis, and immune significance of the critical genes using bioinformatics analysis. The present study demonstrated that NEGR1, NTNG1, XPNPEP2, NTNG2, CD109, OPCML, and PRND are critical genes. The miR-222-3p was highly expressed, probably leading to low NEGR1 and high PRND expression in THCA tissues. Low NEGR1 expression indicated favorable prognosis in THCA patients, and high PRND expression indicated poor prognosis. Seven critical genes were significantly related to gender, age, race, tumor stage, and lymph node metastasis. In addition, the seven-gene biomarker exhibited a certain diagnostic value. Finally, CD109 expression was closely correlated with immune cells, especially B cells and CD4+ T cells. The miR-222-3p and its critical target genes could be promising biomarkers for the prognosis of THCA and may emerge as key regulators of immune infiltration in THCA.

Tumor-derived exosomes, containing multiple nucleic acids and proteins, have been implicated to participate in the interaction between tumor cells and microenvironment. However, the functional involvement of phosphatases in tumor-derived exosomes is not fully understood. We and others previously demonstrated that protein tyrosine phosphatase receptor type O (PTPRO) acts as a tumor suppressor in multiple cancer types. In addition, its role in tumor immune microenvironment remains elusive. Bioinformatical analyses revealed that PTPRO was closely associated with immune infiltration, and positively correlated to M1-like macrophages, but negatively correlated to M2-like macrophages in breast cancer tissues. Co-cultured with PTPRO-overexpressing breast cancer cells increased the proportion of M1-like tumor-associated macrophages (TAMs) while decreased that of M2-like TAMs. Further, we observed that tumor-derived exosomal PTPRO induced M1-like macrophage polarization, and regulated the corresponding functional phenotypes. Moreover, tumor cell-derived exosomal PTPRO inhibited breast cancer cell invasion and migration, and inactivated STAT signaling in macrophages. Our data suggested that exosomal PTPRO inhibited breast cancer invasion and migration by modulating macrophage polarization. Anti-tumoral effect of exosomal PTPRO was mediated by inactivating STAT family in macrophages. These findings highlight a novel mechanism of tumor invasion regulated by tumor-derived exosomal tyrosine phosphatase, which is of translational potential for the therapeutic strategy against breast cancer.

BackgroundThe burden of breast cancer has been increasing globally. The epidemiology burden and trends need to be updated. This study aimed to update the burden and trends of breast cancer incidences, deaths, and disability-adjusted life-years (DALYs) from 1990 to 2019, using the Global Burden of Disease 2019 study.MethodsThe data of incidences, deaths, DALYs, and age-standardized rates were extracted. Estimated annual percentage changes were used to quantify the trends of age-standardized rates. Besides, the population attributable fractions of the risk factors of breast cancer were also estimated.ResultsGlobally, the incidences of breast cancer increased to 2,002,354 in 2019. High social-development index (SDI) quintiles had the highest incidence cases with a declining trend in age-standardized incidence rate. In 2019, the global deaths and DALYs of breast cancer increased to 700,660 and 20,625,313, respectively. From 1990 to 2019, the age-standardized mortality rates and age-standardized DALY rates declined globally, especially in high and high-middle SDI quintiles. Besides, the trends varied from different regions and countries. The proportion of the patients in the 70+ years age group increased globally. Deaths of breast cancer attributable to high fasting plasma glucose and high body mass index increased globally, and high fasting plasma glucose was the greatest contributor to the global breast cancer deaths.ConclusionThe burden of breast cancer in higher SDI quintiles had gone down while the burden was still on the rise in lower SDI quintiles. It is necessary to appeal to the public to decrease the exposure of the risk factors.

OBJECTIVE: Intestinal microbiota plays a vital role in the pathogenesis of colorectal cancer (CRC), which is crucial for assessing the risk and prognosis of CRC. Most studies regarding human gut microbiota mainly based on the feces, but the exact composition of microbiota vary significantly due to fecal composition is easily affected by many factors. We aim to evaluate whether intestinal lavage fluid (IVF) is a better substitution mirroring the gut microbiota. METHODS: We performed 16S rRNA gene analysis on fecal and IVF samples from 30 CRC patients and 25 healthy individuals, comparison in luminal (feces) / mucosal (IVF) adherent bacterial community profiles were analyzed. RESULTS: The difference between feces and IVF were observed, including the diversity and abundance of pathogenic bacteria (either in single strain or in co-occurrence pattern). IVF group shared 605 OTUs with the fecal group, but there was 94 OTUs only observed in fecal samples, while 247 OTUs were mainly existing in the IVF group. Among them, 27 vital bacterial species detected in IVF, while 10 critical species detected in fecal samples. The co-occurrence bacteria Fusobacteria Cluster and Proteobacteria Cluster 2 significantly increased in IVF than in control (P

Aim. A lower ratio of creatinine to body weight (Cr/BW) is considered the independent risk factor for incident nonalcoholic fatty liver disease (NAFLD). However, the relationship between the Cr/BW ratio and NAFLD among individuals without obesity and dyslipidemia and how this relationship is impacted by age are still ambiguous. Therefore, we explored the effect of the Cr/BW ratio on the incident NAFLD among Chinese without obesity and dyslipidemia of different age groups. Methods. A total of 9756 participants without NAFLD at baseline were included and grouped by the median value (1.32) of the Cr/BW ratio. Then, a further analysis was stratified by age (60 years old). The primary outcome was new-onset NAFLD. Results. After a median follow-up of 2.76 years, 844 (8.7%) participants developed NAFLD. The elderly had a higher person-years incidence rate and cumulative incidence rate than the nonelderly. A high Cr/BW ratio showed a lower cumulative incidence compared to a low Cr/BW ratio for the whole population (P=0.039) and the nonelderly group (P=0.008). After being adjusted for multivariate variables, the lower Cr/BW ratio was the independent risk factor for incident NAFLD in the nonelderly (HR 0.718, 95% CI 0.548-0.942), instead of the elderly. Conclusions. The Cr/BW ratio has a negative relationship with incident NAFLD among nonobese Chinese without dyslipidemia before the age of 60.

In recent years, anti-PD-1/anti-PD-L1 has been considered to be a valuable therapeutic target and prognostic indicator for triple-negative breast cancer. We analyzed all publications published in the field fromtheir inception until the present day in order to determine the current research status and hotspots. All related publications were searched on the Web of Science. Our research used R-studio (bibliometrix package), VOSviewer, and CiteSpace to analyze and obtain annual publications and citation information, articles, highest publication countries and affiliations, influential journals and authors, keyword analysis, and keyword bursts. In total, 851 documents were retrieved including 628 articles and 223 review articles. The output of publications increased year by year from 2013 to 2021. However, the average article citation times reached the top in 2014 but generally showed a downward trend from 2014 to 2021. It was an article written by Schmid et al. in 2018 that received the most citations. With regard to publications, citations, and link strength, among the top countries was the United States. Cancers was the most published journal. Schmid and Loi ranked top in total citations and h-index. Schmid has the largest M-index and Loi has the most publication. The keywords that received the most attention were "Immunotherapy", "PD-L1", "Triple-negative breast cancer", "Tumor-infiltrating lymphocytes", and "Expression". According to the report, this current research focuses on immunotherapy for triple-negative breast cancer and the expression of PD-L1 and tumor-infiltrating lymphocytes (TILs). Pembrolizumab and Atezolizumab plus chemotherapy have completed the Phase 3 clinical trial. However, the biomarkers were limited in predicting the treatment prognosis. Through the scientometric analysis, we can understand the current research status and potential research points in this filed and provide research direction for researchers. [ABSTRACT FROM AUTHOR]

Background: Poor immunogenicity and extensive immunosuppressive T-cell infiltration in the tumor immune microenvironment (TIME) have been identified as potential barriers to immunotherapy success in "immune-cold" breast cancers. Thus, it is crucial to identify biomarkers that can predict immunotherapy efficacy. Protein tyrosine phosphatase receptor type O (PTPRO) regulates multiple kinases and pathways and has been implied to play a regulatory role in immune cell infiltration in various cancers. Methods: ESTIMATE and single-sample gene set enrichment analysis (ssGSEA) were performed to uncover the TIME landscape. The correlation analysis of PTPRO and immune infiltration was performed to characterize the immune features of PTPRO. Univariate and multivariate Cox analyses were applied to determine the prognostic value of various variables and construct the PTPRO-related CD8+ T-cell signatures (PTSs). The Kaplan-Meier curve and the receiver operating characteristic (ROC) curve were used to estimate the performance of PTS in assessing prognosis and immunotherapy response in multiple validation datasets. Results: High PTPRO expression was related to high infiltration levels of CD8+ T cells, as well as macrophages, activated dendritic cells (aDCs), tumor-infiltrating lymphocytes (TILs), and Th1 cells. Given the critical role of CD8+ T cells in the TIME, we focused on the impact of PTPRO expression on CD8+ T-cell infiltration. The prognostic PTS was then constructed using the TCGA training dataset. Further analysis showed that the PTS exhibited favorable prognostic performance in multiple validation datasets. Of note, the PTS could accurately predict the response to immune checkpoint inhibitors (ICIs). Conclusion: PTPRO significantly impacts CD8+ T-cell infiltration in breast cancer, suggesting a potential role of immunomodulation. PTPRO-based PTS provides a new immune cell paradigm for prognosis, which is valuable for immunotherapy decisions in cancer patients. [ABSTRACT FROM AUTHOR]

Objective: To identify immune-related long non-coding RNAs (lncRNAs) in papillary thyroid cancer (PTC). Methods: The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to obtain the gene expression profile. Immune-related lncRNAs were screened from the Molecular Signatures Database v4.0 (MsigDB). We performed a survival analysis of critical lncRNAs. Further, the function of prognostic lncRNAs was inferred using the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) to clarify the possible mechanisms underlying their predictive ability. The assessment was performed in clinical samples and PTC cells. Results: We obtained 4 immune-related lncRNAs, 15 microRNAs (miRNAs), and 375 mRNAs as the key mediators in the pathophysiological processes of PTC from the GEO database. Further, Lasso regression analysis identified seven prognostic markers (LINC02550, SLC26A4-AS1, ACVR2B-AS1, AC005479.2, LINC02454, and AL136366.1), most of which were related to tumor development. The KEGG pathway enrichment analysis showed different, changed genes mainly enriched in the cancer-related pathways, PI3K-Akt signaling pathway, and focal adhesion. Only SLC26A4-AS1 had an intersection in the results of the two databases. Conclusion: LncRNA SLC26A4-AS1, which is the most associated with prognosis, may play an oncogenic role in the development of PTC. [ABSTRACT FROM AUTHOR]

Restores TBP function 1 (Rtf1) is generally considered to be a subunit of the Paf1 complex (PAF1C), a multifunctional protein complex involved in histone modification and transcriptional or posttranscriptional regulation. Rtf1, however, is not stably associated with the PAF1C inmost species except Saccharomyces cerevisiae, and its biochemical functions are not well understood. Here, we show that human Rtf1 is a transcription elongation factor that may function independently of the PAF1C. Rtf1 requires "Rtf1 coactivator" activity, which is most likely unrelated to the PAF1C or DSIF, for transcriptional activation in vitro. A mutational study revealed that the Plus3 domain of human Rtf1 is critical for its coactivator-dependent function. Transcriptome sequencing (RNA-seq) and chromatin immunoprecipitation studies in HeLa cells showed that Rtf1 and the PAF1C play distinct roles in regulating the expression of a subset of genes. Moreover, contrary to the finding in S. cerevisiae, the PAF1C was apparently recruited to the genes examined in an Rtf1-independent manner. The present study establishes a role for human Rtf1 as a transcription elongation factor and highlights the similarities and differences between the S. cerevisiae and human Rtf1 proteins. [ABSTRACT FROM AUTHOR]

Brazil, Russia, India, China and South Africa (BRICS) account for nearly half of the world's population. We aimed to analyse mortality trends of breast cancer across the BRICS countries from 1990 to 2019. Breast cancer mortality estimates were obtained from the Global Burden of Disease Study 2019. An age-period-cohort model was adopted to estimate age, period and cohort effects on breast cancer mortality between 1990 and 2019. Results showed that breast cancer caused 0.23 million deaths across the BRICS countries in 2019, accounting for 32.7% of the total death caused by breast cancer worldwide. China had the largest number of deaths, followed by India. All five BRICS countries showed positive percentage changes in deaths from 1990 to 2019. The age-standardized mortality rates (ASMRs) in India, South Africa and China presented increased trends. South Africa presented the fastest increased rate with age. Downward period trends were observed in China, South Africa, Brazil and Russia, while an upward trend was seen in India, with the period rate ratio increasing from 0.95 to 1.17. In conclusion, the disease burden of breast cancer is still heavy across the BRICS countries. It is important to pay more attention to elderly patients. The increasing disease burden must be addressed multidimensionally, incorporating screening and early detection, timely and sufficient treatment and appropriate prevention. [ABSTRACT FROM AUTHOR]