Macrophage Tim-3 maintains intestinal homeostasis in DSS-induced colitis by suppressing neutrophil necroptosis.

T-cell immunoglobulin domain and mucin domain-3 (Tim-3) is a versatile immunomodulator that protects against intestinal inflammation. Necroptosis is a type of cell death that regulates intestinal homeostasis and inflammation. The mechanism(s) underlying the protective role of macrophage Tim-3 in intestinal inflammation is unclear; thus, we investigated whether specific Tim-3 knockdown in macrophages drives intestinal inflammation via necroptosis. Tim-3 protein and mRNA expression were assessed via double immunofluorescence staining and single-cell RNA sequencing (sc-RNA seq), respectively, in the colonic tissues of patients with inflammatory bowel disease (IBD) and healthy controls. Macrophage-specific Tim3-knockout (Tim-3M-KO) mice were generated to explore the function and mechanism of Tim-3 in dextran sodium sulfate (DSS)-induced colitis. Necroptosis was blocked by pharmacological inhibitors of receptor-interacting protein kinase (RIP)1, RIP3, and reactive oxygen species (ROS). Additionally, in vitro experiments were performed to assess the mechanisms of neutrophil necroptosis induced by Tim-3 knockdown macrophages. Although Tim-3 is relatively inactive in macrophages during colon homeostasis, it is highly active during colitis. Compared to those in controls, Tim-3M-KO mice showed increased susceptibility to colitis, higher colitis scores, and increased pro-inflammatory mediator expression. Following the administration of RIP1/RIP3 or ROS inhibitors, a significant reduction in intestinal inflammation symptoms was observed in DSS-treated Tim-3M-KO mice. Further analysis indicated the TLR4/NF-κB pathway in Tim-3 knockdown macrophages mediates the TNF-α-induced necroptosis pathway in neutrophils. Macrophage Tim-3 regulates neutrophil necroptosis via intracellular ROS signaling. Tim-3 knockdown macrophages can recruit neutrophils and induce neutrophil necroptosis, thereby damaging the intestinal mucosal barrier and triggering a vicious cycle in the development of colitis. Our results demonstrate a protective role of macrophage Tim-3 in maintaining gut homeostasis by inhibiting neutrophil necroptosis and provide novel insights into the pathogenesis of IBD.

Accurate estimation of biological age and its application in disease prediction using a multimodal image Transformer system.

Aging in an individual refers to the temporal change, mostly decline, in the body's ability to meet physiological demands. Biological age (BA) is a biomarker of chronological aging and can be used to stratify populations to predict certain age-related chronic diseases. BA can be predicted from biomedical features such as brain MRI, retinal, or facial images, but the inherent heterogeneity in the aging process limits the usefulness of BA predicted from individual body systems. In this paper, we developed a multimodal Transformer-based architecture with cross-attention which was able to combine facial, tongue, and retinal images to estimate BA. We trained our model using facial, tongue, and retinal images from 11,223 healthy subjects and demonstrated that using a fusion of the three image modalities achieved the most accurate BA predictions. We validated our approach on a test population of 2,840 individuals with six chronic diseases and obtained significant difference between chronological age and BA (AgeDiff) than that of healthy subjects. We showed that AgeDiff has the potential to be utilized as a standalone biomarker or conjunctively alongside other known factors for risk stratification and progression prediction of chronic diseases. Our results therefore highlight the feasibility of using multimodal images to estimate and interrogate the aging process.

Reinforced medication adherence improves Helicobacter pylori eradication rate in developing countries: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The eradication rate of Helicobacter pylori (H. pylori) remains variable for the same eradication regime even in the identical region, especially in developing countries. Herein, we conducted a systematic review to assess the effect of reinforced medication adherence on H. pylori eradication rate in developing countries. MATERIALS AND METHODS: A systematic review was conducted in literature databases to identify relevant randomized controlled trials (RCTs) from inception to March 2023. The core indicator was the changes in eradication rate after enhanced adherence. A meta-analysis was performed to estimate the pooled relative risk (RR) or weighted mean difference (WMD) with 95% confidence intervals (CI). RESULTS: Nineteen RCTs that included a total of 3286 patients were assessed. The measures to enhance compliance were mainly through face-to-face communication, phone calls, text messages, and social software. Compared with the control group, patients received reinforced measures showed a better medication adherence (89.6% vs. 71.4%, RR = 1.26 95% CI: 1.16-1.37), higher H. pylori eradication rate (intention-to-treat analysis: 80.2% vs. 65.9%, RR = 1.25, 95% CI: 1.12-1.31; per-protocol analysis: 86.8% vs. 74.8%, RR = 1.16, 95% CI: 1.09-1.23), higher symptom relief rates (81.8% vs. 65.1%, RR = 1.23, 95% CI: 1.09-1.38), higher degree of satisfaction (90.4% vs. 65.1%, RR = 1.26, 95% CI: 1.19-1.35), higher disease knowledge rates (SMD = 1.82, 95% CI: 0.77-2.86, p = 0.0007), and lower incidence of total adverse events (27.3% vs. 34.7%, RR = 0.72, 95% CI: 0.52-0.99). CONCLUSION: Based on available evidence, reinforced medication adherence as a nonnegligible measure improves H. pylori eradication rate in developing countries.

Spatial transcriptomics reveals the heterogeneity and FGG+CRP+ inflammatory cancer-associated fibroblasts replace islets in pancreatic ductal adenocarcinoma.

Background: Understanding the spatial heterogeneity of the tumor microenvironment (TME) in pancreatic cancer (PC) remains challenging. Methods: In this study, we performed spatial transcriptomics (ST) to investigate the gene expression features across one normal pancreatic tissue, PC tissue, adjacent tumor tissue, and tumor stroma. We divided 18,075 spatial spots into 22 clusters with t-distributed stochastic neighbor embedding based on gene expression profiles. The biological functions and signaling pathways involved in each cluster were analyzed with gene set enrichment analysis. Results: The results revealed that KRT13+FABP5+ malignant cell subpopulation had keratinization characteristics in the tumor tissue. Fibroblasts from adjacent tumor tissue exhibited a tumor-inhibiting role such as "B-cell activation" and "positive regulation of leukocyte activation." The FGG+CRP+ inflammatory cancer-associated fibroblasts replaced the islets in tumor stroma. During PC progression, the damage to pancreatic structure and function was heavier in the pancreatic exocrine (AMYA2+PRSS1+) than in the endocrine (INS+GCG+). Conclusion: Our results revealed the spatial heterogeneity of dynamic changes and highlighted the significance of impaired exocrine function in PC.

Knowledge landscape of tumor-associated macrophage research: A bibliometric and visual analysis.

Background and aims: Tumor-associated macrophage (TAM) is a highly abundant immune population in tumor microenvironment, which plays an important role in tumor growth and progression. The aim of our study was to explore the development trends and research hotspots of TAM by bibliometric method. Methods: The publications related to TAM were obtained from the Web of Science Core Collection database. Bibliometric analysis and visualization were conducted using VOSviewer, CiteSpace and R software. Results: A total of 6,405 articles published between 2001 and 2021 were included. The United States and China received the most citations, whereas the University of Milan, the university of California San Francisco and Sun Yat-sen University were the main research institutions. Mantovani, Alberto from Humanitas University was the most productive authors with the most citations. Cancer Research published the most articles and received the most co-citations. Activation, angiogenesis, breast cancer, NF-κB and endothelial growth factor were important keywords in TAM research. Among them, PD-1/L1, nanoparticle, PI3Kγ, resistance and immune microenvironment have become the focus of attention in more recent research. Conclusions: The research on TAM is rapidly evolving with active cooperation worldwide. Anticancer therapy targeting TAM is emerging and promising area of future research, especially in translational application. This may provide guidance and new insights for further research in the field of TAM.

A bibliometric analysis of inflammatory bowel disease and COVID-19 researches.

Background: Patients with inflammatory bowel disease (IBD) often require immunosuppressive therapy and are hence susceptible to various opportunistic viral and bacterial infections. In this regard, many studies on IBD and COVID-19 have been conducted. However, no bibliometric analysis has been performed. This study provides a general overview of IBD and COVID-19. Methods: Publications about IBD and COVID-19 from 2020 to 2022 were retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was performed using VOSviewer, CiteSpace, and HistCite. Results: A total of 396 publications were retrieved and considered in this study. The maximum number of publications were from the United States, Italy, and England, and the contributions of these countries were significant. Kappelman ranked first in article citations. The Icahn School of Medicine at Mount Sinai and Inflammatory Bowel Diseases were the most prolific affiliation and journal, respectively. The most influential research topics were "management", "impact", "vaccination", and "receptor". The following keywords represented research frontiers: "depression", "the quality of life of IBD patients", "infliximab", "COVID-19 vaccine", and "second vaccination". Conclusions: Over the past 3 years, most studies on IBD and COVID-19 have focused on clinical research. In particular, topics such as "depression", "the quality of life of IBD patients", "infliximab", "COVID-19 vaccine", and "second vaccination" were noted to have received much attention recently. Future research should focus on our understanding of the immune response to COVID-19 vaccination in biologically treated patients, the psychological impact of COVID-19, IBD management guidelines, and the long-term impact of COVID-19 in IBD patients. This study will provide researchers with a better understanding of research trends on IBD during COVID-19.

Effects of different preservation methods of human iliac veins.

With the progress of vascular anastomosis technology, the radical resection surgery of cancer combining with vascular resection and reconstruction has been focused by surgeon. As a natural substitute material for blood vessel, vascular allografts have good vascular compliance and histocompatibility. Generally, the donated veins could not be used immediately, and need to be well preserved. So, it is greatly significant to do research in the preservation effects of different preservation methods on veins. In this study, the effects of different preservative methods of human iliac veins were compared and analyzed in terms of cell viability, vascular wall structure and tension resistance. The donated human iliac veins were randomly divided into three groups: Cold Storage Group (4 °C) (CSG), Frozen Storage Group (-186 °C) (FSG)and Fresh Control Group (FCG). Six detection time-points of preservation for 1, 3, 5, 7, 14, 28 days were set respectively. There are ten samples in each group and each time-point separately. Survival and apoptosis of vascular cell were evaluated by MTT assay and Tunel fluorescence staining. Tensile test was used to evaluate mechanical properties of vessels. The changes of vascular endothelial cells, smooth muscle cells, collagen fibers and elastic fibers were evaluated by HE staining, Masson staining and EVG staining. Furthermore, the changes of organelles were observed by transmission electron microscope. With the extension of preservation period, the vascular cell viability and tension resistance of two groups decreased, and the apoptotic cells increased gradually. The apoptosis index of CSG was higher than FSG at each time point (P < 0.05). In terms of cell viability, CSG was higher within 3 days (P < 0.05), both groups were same between 3 and 14 days, and then CSG lower than FSG after 14 days (P < 0.05). In terms of tension resistance, CSG was stronger than FSG (P < 0.05) in first 7 days, both groups were same in 2nd week, and then CSG was weaker in 4th week (P < 0.05). In terms of vascular wall structure, in CSG, vascular endothelial cells were damaged and shed, smooth muscle cells were edema after 14 days, but the cell membrane and intercellular connection were still intact. In 4th week, endothelial cells were completely damaged and shed, the boundary of smooth muscle cell membrane was unclear, intercellular connection was damaged. Moreover, organelles were destroyed and disappeared, perinuclear condensation of chromatin was observed, and some cells had incomplete nuclear membrane or nuclear fragmentation; However, there were no obvious changes in the FSG within 28 days. Finally, local exfoliation and destruction of endothelial cells and edema-like changes of organelles were observed; the collagen fibers and elastic fibers of blood vessels in the two groups had no obvious damage and change within 28 days. For excised human iliac vein, cold and frozen storage can effectively preserve the cell viability, wall structure and tension resistance of blood vessels. With the extension of preservation time, the related performance of vessels declined in varying degrees. Within first week, the effect of cold storage is better than frozen storage, but frozen storage is significantly better than cold storage after 2 weeks.

Construction of a novel choline metabolism-related signature to predict prognosis, immune landscape, and chemotherapy response in colon adenocarcinoma.

Background: Colon adenocarcinoma (COAD) is a common digestive system malignancy with high mortality and poor prognosis. Accumulating evidence indicates that choline metabolism is closely related to tumorigenesis and development. However, the efficacy of choline metabolism-related signature in predicting patient prognosis, immune microenvironment and chemotherapy response has not been fully clarified. Methods: Choline metabolism-related differentially expressed genes (DEGs) between normal and COAD tissues were screened using datasets from The Cancer Genome Atlas (TCGA), Kyoto Encyclopedia of Genes and Genomes (KEGG), AmiGO2 and Reactome Pathway databases. Two choline metabolism-related genes (CHKB and PEMT) were identified by univariate and multivariate Cox regression analyses. TCGA-COAD was the training cohort, and GSE17536 was the validation cohort. Patients in the high- and low-risk groups were distinguished according to the optimal cutoff value of the risk score. A nomogram was used to assess the prognostic accuracy of the choline metabolism-related signature. Calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC) were used to improve the clinical applicability of the prognostic signature. Gene Ontology (GO) and KEGG pathway enrichment analyses of DEGs in the high- and low-risk groups were performed. KEGG cluster analysis was conducted by the KOBAS-i database. The distribution and expression of CHKB and PEMT in various types of immune cells were analyzed based on single-cell RNA sequencing (scRNA-seq). The CIBERSORT and ESTIMATE algorithms evaluated tumor immune cell infiltration in the high- and low-risk groups. Evaluation of the half maximal inhibitory concentration (IC50) of common chemotherapeutic drugs based on the choline metabolism-related signature was performed. Small molecule compounds were predicted using the Connectivity Map (CMap) database. Molecular docking is used to simulate the binding conformation of small molecule compounds and key targets. By immunohistochemistry (IHC), Western blot, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) experiments, the expression levels of CHKB and PEMT in human, mouse, and cell lines were detected. Results: We constructed and validated a choline metabolism-related signature containing two genes (CHKB and PEMT). The overall survival (OS) of patients in the high-risk group was significantly worse than that of patients in the low-risk group. The nomogram could effectively and accurately predict the OS of COAD patients at 1, 3, and 5 years. The DCA curve and CIC demonstrate the clinical utility of the nomogram. scRNA-seq showed that CHKB was mainly distributed in endothelial cells, while PEMT was mainly distributed in CD4+ T cells and CD8+ T cells. In addition, multiple types of immune cells expressing CHKB and PEMT differed significantly. There were significant differences in the immune microenvironment, immune checkpoint expression and chemotherapy response between the two risk groups. In addition, we screened five potential small molecule drugs that targeted treatment for COAD. Finally, the results of IHC, Western blot, and qRT-PCR consistently showed that the expression of CHKB in human, mouse, and cell lines was elevated in normal samples, while PMET showed the opposite trend. Conclusion: In conclusion, we constructed a choline metabolism-related signature in COAD and revealed its potential application value in predicting the prognosis, immune microenvironment, and chemotherapy response of patients, which may lay an important theoretical basis for future personalized precision therapy.

Appealing to Individual Fears or Social Norms: How Can the Public Be Persuaded to Accept COVID-19 Vaccination through Risk Communication?

In the context of the COVID-19 pandemic, improving the public's understanding of the increased efficacy and safety of the COVID-19 vaccines through scientific risk communication campaigns, promoting the public's acceptance and willingness to receive COVID-19 vaccines, and forming collective actions at the social level will deeply impact on the effect of COVID-19 prevention in various countries, which is also a key factor that governments need to address urgently. Previous research on risk communication has mostly focused on microscopic perspectives of how to stimulate individual self-protection behaviors by awakening threat and efficacy perceptions; however, a lack of observation of social collective actions means there is a risk of failure regarding COVID-19 epidemic reduction and prevention. In this regard, this study was based on the issue of vaccination in the context of the COVID-19 epidemic through a highly regulated and controlled research experiment in China (n = 165), which was designed to examine the impact of two risk communication frameworks, appealing to individual fears and appealing to social norms, on the public's acceptance and recommendations of COVID-19 vaccines, thus outlining the path of action from individual protection to collective epidemic prevention. Both the "fear appeals" framework and the "social norms" framework were found to have a positive effect on the Chinese public's vaccination acceptance. Specifically, social norms information may increase vaccination acceptance by enhancing the public's perceptions of social responsibility, while fear appeals information may reduce their perceptions of threat and social pressure to get the vaccine. Female and highly educated groups were more likely to refuse to recommend vaccination after reading the risk communication information. These results can be a useful supplement to the theory and practice of risk communication.

Bibliometric analysis of publications on necroptosis from 2001 to 2021.

Background: Necroptosis plays an important role in inflammation, cancer, and neurodegenerative diseases. In recent years, the number of studies related to necroptosis has increased and research has become increasingly in-depth. This study aimed to summarize the research conducted since 2001 to discover hotspots and trends in the field of necroptosis. Methods: The Web of Science Core database was used to identify global publications on necroptosis from 2001 to 2021. Bibliometric analysis was performed using Rstudio, VOSviewer, and CiteSpace. Results: The number of publications related to necroptosis gradually increased from 2001 to 2021. Vandenabeele P had the most publications at 45. Yuan JY had the most citations at 5,901. Necroptosis research has been dominated by China and Chinese institutions. Cell Death and Disease had the highest number of related publications among the examined journals. Seven of the top 10 most cited papers had more than 500 citations. Necroptosis, cell death, autophagy, injury, cancer, activated B cell nuclear factor kappa-light chain enhancer, and oxidative stress were important keywords in keyword analysis. Recent research has increasingly focused on breast cancer, receptor-interacting serine/threonine protein kinase 1, modulation, pseudokinase mixed lineage kinase domain-like protein, membrane, protection, and cycle. Conclusion: Interest in necroptosis-related research continues to increase steadily, and there is close cooperation between countries and institutions in the field of necroptosis. The study of necroptosis-related molecules and mechanisms, and the relationship between necroptosis and cancer, may be hotspots and directions in future research.

Identification of a glycolysis- and lactate-related gene signature for predicting prognosis, immune microenvironment, and drug candidates in colon adenocarcinoma.

Background: Colon adenocarcinoma (COAD), a malignant gastrointestinal tumor, has the characteristics of high mortality and poor prognosis. Even in the presence of oxygen, the Warburg effect, a major metabolic hallmark of almost all cancer cells, is characterized by increased glycolysis and lactate fermentation, which supports biosynthesis and provides energy to sustain tumor cell growth and proliferation. However, a thorough investigation into glycolysis- and lactate-related genes and their association with COAD prognosis, immune cell infiltration, and drug candidates is currently lacking. Methods: COAD patient data and glycolysis- and lactate-related genes were retrieved from The Cancer Genome Atlas (TCGA) and Gene Set Enrichment Analysis (GSEA) databases, respectively. After univariate Cox regression analysis, a nonnegative matrix factorization (NMF) algorithm was used to identify glycolysis- and lactate-related molecular subtypes. Least absolute shrinkage and selection operator (LASSO) Cox regression identified twelve glycolysis- and lactate-related genes (ADTRP, ALDOB, APOBEC1, ASCL2, CEACAM7, CLCA1, CTXN1, FLNA, NAT2, OLFM4, PTPRU, and SNCG) related to prognosis. The median risk score was employed to separate patients into high- and low-risk groups. The prognostic efficacy of the glycolysis- and lactate-related gene signature was assessed using Kaplan-Meier (KM) survival and receiver operating characteristic (ROC) curve analyses. The nomogram, calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC) were employed to improve the clinical applicability of the prognostic signature. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on differentially expressed genes (DEGs) from the high- and low-risk groups. Using CIBERSORT, ESTIMATE, and single-sample GSEA (ssGSEA) algorithms, the quantities and types of tumor-infiltrating immune cells were assessed. The tumor mutational burden (TMB) and cytolytic (CYT) activity scores were calculated between the high- and low-risk groups. Potential small-molecule agents were identified using the Connectivity Map (cMap) database and validated by molecular docking. To verify key core gene expression levels, quantitative real-time polymerase chain reaction (qRT-PCR) assays were conducted. Results: We identified four distinct molecular subtypes of COAD. Cluster 2 had the best prognosis, and clusters 1 and 3 had poor prognoses. High-risk COAD patients exhibited considerably poorer overall survival (OS) than low-risk COAD patients. The nomogram precisely predicted patient OS, with acceptable discrimination and excellent calibration. GO and KEGG pathway enrichment analyses of DEGs revealed enrichment mainly in the "glycosaminoglycan binding," "extracellular matrix," "pancreatic secretion," and "focal adhesion" pathways. Patients in the low-risk group exhibited a larger infiltration of memory CD4+ T cells and dendritic cells and a better prognosis than those in the high-risk group. The chemotherapeutic agent sensitivity of patients categorized by risk score varied significantly. We predicted six potential small-molecule agents binding to the core target of the glycolysis- and lactate-related gene signature. ALDOB and APOBEC1 mRNA expression was increased in COAD tissues, whereas CLCA1 and OLFM4 mRNA expression was increased in normal tissues. Conclusion: In summary, we identified molecular subtypes of COAD and developed a glycolysis- and lactate-related gene signature with significant prognostic value, which benefits COAD patients by informing more precise and effective treatment decisions.

Case report: Nocardia farcinica pneumonia in early-stage post liver transplantation.

Background: Liver transplantation is a well-established treatment for end-stage liver disease. The evolution of immunosuppressants has supported the recent advances in this field. However, this leads to immunosuppression and increases the risk for infections. Nocardia is an aerobic gram-positive bacillus, which can cause multi-systemic or multi-organ infections. Nocardia is an opportunistic pathogen that principally affects immunosuppressed patients. Case presentation: Herein, we present a case of Nocardia farcinica pneumonia in a patient at early-stage post-liver transplantation. Following appropriate microbiological tests and imaging, the diagnosis was finally confirmed. A full recovery was achieved after optimal antibiotic therapy of sulfamethoxazole, minocycline, and amikacin. Conclusions: Nocardia farcinica pneumonia is a rare and life-threatening disease, especially in patients after liver transplantation. Imaging and microbiological tests are helpful for the early diagnosis of the disease. Trimethoprim-sulfamethoxazole (TMP-SMX) as part of first-line therapy for nocardiosis is recommended.

An Intratumor Heterogeneity-Related Signature for Predicting Prognosis, Immune Landscape, and Chemotherapy Response in Colon Adenocarcinoma.

Background: Colon adenocarcinoma (COAD) is a frequent malignancy of the digestive system with a poor prognosis and high mortality rate worldwide. Intratumor heterogeneity (ITH) is associated with tumor progression, poor prognosis, immunosuppression, and therapy resistance. However, the relationship between ITH and prognosis, the immune microenvironment, and the chemotherapy response in COAD patients remains unknown, and this knowledge is urgently needed. Methods: We obtained clinical information and gene expression data for COAD patients from The Cancer Genome Atlas (TCGA) database. The DEPTH2 algorithm was utilized to evaluate the ITH score. X-tile software was used to determine the optimal cutoff value of the ITH score. The COAD patients were divided into high- and low-ITH groups based on the cutoff value. We analyzed prognosis, tumor mutation burden (TMB), gene mutations, and immune checkpoint expression between the high- and low-ITH groups. Differentially expressed genes (DEGs) in the high- and low-ITH groups were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. We performed univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses to screen the prognosis-related genes for the construction of an ITH-related prognostic signature. The nomogram was used to predict the overall survival (OS) of COAD patients. The protein-protein interaction (PPI) network was constructed by using the GeneMANIA database. Principal component analysis (PCA) and single-sample gene set enrichment analysis (ssGSEA) were employed to explore the differences in biological pathway activation status between the high- and low-risk groups. The proportion and type of tumor-infiltrating immune cells were evaluated by the CIBERSORT and ESTIMATE algorithms. Additionally, we assessed the chemotherapy response and predicted small-molecule drugs for treatment. Finally, the expression of the prognosis-related genes was validated by using the UALCAN database and Human Protein Atlas (HPA) database. Results: The OS of the high-ITH group was worse than that of the low-ITH group. A positive correlation between ITH and TMB was identified. In subgroups stratified by age, gender, and tumor stage, the OS of the low-ITH group remained better than that of the high-ITH group. There were dramatic differences in the mutated genes, single nucleotide variant classes, variant types, immune checkpoints and cooccurring and mutually exclusive mutations of the DEGs between the high- and low-ITH groups. Based on the DEGs between the high- and low-ITH groups, we constructed a five-gene signature consisting of CEACAM5, ENO2, GABBR1, MC1R, and SLC44A4. The COAD patients were divided into high- and low-risk groups according to the median risk score. The OS of the high-risk group was worse than that of the low-risk group. The nomogram was used to accurately predict the 1-, 3- and 5-year OS of COAD patients and showed good calibration and moderate discrimination ability. The stromal score, immune score, and ESTIMATE score of the high-risk group were significantly higher than those of the low-risk group, whereas tumor purity showed the opposite trend. The patients classified by the risk score had distinguishable sensitivity to chemotherapeutic drugs. Finally, two public databases confirmed that CEACAM5 and SLC44A4 were upregulated in normal tissues compared with COAD tissues, and ENO2, GABBR1, and MC1R were upregulated in COAD tissues compared with normal tissues. Conclusion: Overall, we identified an ITH-related prognostic signature for COAD that was closely related to the tumor microenvironment and chemotherapy response. This signature may help clinicians make more personalized and precise treatment decisions for COAD patients.

The Interferon Gamma-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Colon Adenocarcinoma.

Colon adenocarcinoma (COAD) is one of the most common clinically malignant tumours of the digestive system, with high incidence and mortality and poor prognosis. Interferon-gamma (IFN-γ) and long noncoding RNAs (lncRNAs) have prognostic values and were closely associated with immune microenvironment in COAD. Thus, identifying IFN-γ-related lncRNAs may be valuable in predicting the survival of patients with COAD. In this study, we identified IFN-γ-related lncRNAs and divided COAD patients from the Cancer Genome Atlas (TCGA) database into training and validation sets. Pearson's correlation analysis and least absolute shrinkage and selection operator (LASSO) Cox regression were performed to select IFN-γ-related lncRNA-associated prognoses. Thirteen lncRNAs (AC025165.8, AC091633.3, FENDRR, LINC00882, LINC01828, LINC01829, MYOSLID, RP11-154H23.4, RP11-20J15.3, RP11-324L17.1, RP11-342A23.2, RP11-805I24.3, SERTAD4-AS1) were identified to construct an IFN-γ-related lncRNA prognostic signature in TCGA training (n =213) and validation (n =213) cohorts. COAD patient risk scores were calculated and classified into high- and low-risk groups based on the median value of the risk scores in each dataset. We compared the overall survival (OS) of patients stratified by age, gender, and stage. The OS in the high-risk group was significantly shorter than that in the low-risk group. In addition, the clinical nomogram incorporating the prognostic signature and clinical features showed a high concordance index of 0.78 and accurately predicted 1-, 3-, and 5-year survival times among COAD patients in the high- and low-risk groups. Based on the risk model, the high- and low-risk groups exhibited distinct differences in the immune system by gene set enrichment analysis (GSEA) functional annotation, and differentially expressed genes (DEGs) between the high- and low-risk groups were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. We investigated the expression of multiple immune checkpoint genes in the high- and low-risk groups and plotted Kaplan-Meier survival curves, indicating that immune checkpoint genes, such as LAG3 and PD. L1, STING and TIM 3, were also expressed differently between the two risk groups. Subsequently, there were dramatic differences in mutated genes, SNV (single nucleotide variants) classes, variant types and variant allele frequencies between low- and high-risk patients with COAD. Patients stratified by risk scores had different sensitivities to common chemotherapeutic agents. Finally, we used quantitative real-time polymerase chain reaction (qRT-PCR) assays to demonstrate that three lncRNAs were significantly differentially expressed in COAD tissues and adjacent normal tissues. Considered together, a thirteen-lncRNA prognostic signature has great potential to be a prognostic biomarker and could play an essential role in the immune microenvironment of COAD.

No significant relationship exists between tumor size and prognosis in distant metastatic hepatocellular carcinoma: a propensity score matching analysis based on SEER database.

BACKGROUND: Previous studies have shown that tumor size has an impact on the prognosis of hepatocellular carcinoma (HCC). Whether tumor size is related to the prognosis of distant metastatic HCC is unclear. The purpose of this study was to investigate the effect of tumor size on the prognosis of distant metastatic HCC. METHODS: Data on patients with HCC were collected from the (SEER) database of surveillance, epidemiology and final results. Propensity score matching (PSM) was used to reduce confounding factors and comprehensively evaluate the clinicopathological features and prognosis of distant metastatic HCC. RESULTS: There were 189 patients with distant metastatic HCC whose tumor size was ≤ 50 mm and 615 patients with a tumor size > 50 mm. The tumor sizes of distant metastatic HCC patients were associated with race, grade, surgical treatment, N and AFP. The Kaplan-Meier analysis showed that the mortality rate of patients with a tumor size > 50 mm was higher than that of patients with a tumor size ≤ 50 mm (p = 0.00062). However, there were no significant differences in mortality rates after adjusting for confounding variables by using propensity score matching (p = 0.23). CONCLUSION: This propensity score matching study provides the best data in support of the following assertions: tumor size is not an independent prognostic factor for distant metastatic HCC.

The Motivation of Media Users and China's National Media Digitization Construction in the Post-COVID-19 Era.

The sudden arrival of COVID-19 has had an enormous impact on the lives of people around the world, including significant psychological pressure and increased emotional needs. In China, research into user psychology and the motivations of commercial digital media has become more popular, but the national media should pay more attention to user psychology and perform more research on user motivations to improve the effectiveness of communication. We investigated people's internal psychology and motivation for using national media digital platforms in China during the pandemic. We collected data through online questionnaires and analyzed the use of apps of CCTV and The People's Daily by individual users during the pandemic and the psychological needs of national digital media users. In the first stage of our research, we selected national digital media app users through the WeChat platform. In the second stage, more active users were chosen by snowballing upon the original sample. We surveyed 210 participants and ultimately obtained 180 valid samples. We analyzed the data using used SPSS 23.0. The results showed that with the help of digital media platforms and diversified media technology, the Chinese national media not only met the needs of users for information acquisition, but also provided sufficient emotional mutual assistance and comfort to users through the network aggregation formed by digital scene communication.