Comprehensive transcriptome and scRNA-seq analyses uncover the expression and underlying mechanism of SYNJ2 in papillary thyroid carcinoma.

Synaptojanin 2 (SYNJ2) has crucial role in various tumors, but its role in papillary thyroid carcinoma (PTC) remains unexplored. This study first detected SYNJ2 protein expression in PTC using immunohistochemistry method and further assessed SYNJ2 mRNA expression through mRNA chip and RNA sequencing data and its association with clinical characteristics. Additionally, KEGG, GSVA, and GSEA analyses were conducted to investigate potential biological functions, while single-cell RNA sequencing data were used to explore SYNJ2's underlying mechanisms in PTC. Meanwhile, immune infiltration status in different SYNJ2 expression groups were analyzed. Besides, we investigated the immune checkpoint gene expression and implemented drug sensitivity analysis. Results indicated that SYNJ2 is highly expressed in PTC (SMD = 0.66 [95% CI: 0.17-1.15]) and could distinguish between PTC and non-PTC tissues (AUC = 0.74 [0.70-0.78]). Furthermore, the study identified 134 intersecting genes of DEGs and CEGs, mainly enriched in the angiogenesis and epithelial-mesenchymal transition (EMT) pathways. Subsequent analysis showed the above pathways were activated in PTC epithelial cells. PTC patients with high SYNJ2 expression showed higher sensitivity to the six common drugs. Summarily, SYNJ2 may promote PTC progression through angiogenesis and EMT pathways. High SYNJ2 expression is associated with better response to immunotherapy and chemotherapy.

An analysis of the clinical significance of the TKI-resistant gene ZNF687 for hepatocellular carcinoma patients.

BACKGROUND: Novel treatments such as monotherapy and combined immunotherapy significantly extend overall survival (OS) for hepatocellular carcinoma (HCC) patients, but HCC is susceptible to treatment resistance during long-term therapy. The resistance mechanism to targeted drugs in HCC remains ambiguous, making research on HCC drug resistance targets crucial for the development of precision medicine. OBJECTIVES: To investigate the transcriptional features, biological functions and potential clinical value of the tyrosine kinase inhibitor (TKI)-resistant gene ZNF687 in HCC. MATERIAL AND METHODS: The TKI-resistant genes of HCC were identified using clustered regularly interspaced short palindromic repeats (CRISPR) in vitro screening. Then, the dependence of HCC cell lines on ZNF687 was investigated in silico. We collected global mRNA datasets of HCC tissue, integrated the mRNA expression characteristics of ZNF687 in HCC and explored the impact of ZNF687 on HCC patient prognoses using the Kaplan-Meier method (in silico). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses were then conducted, and a connectivity map and molecular docking technology were applied to find the underlying agent opposing ZNF687. RESULTS: In vitro, the guide RNA corresponding to ZNF687 was weakly detected in HCC cells, and ZNF687 deficiency was found to inhibit growth in HCC cell lines. ZNF687 mRNA was overexpressed and had a high discriminatory ability for HCC in 2,975 HCC samples, contrasting with 2,340 non-HCC samples. Moreover, an excessive ZNF687 transcript level was related to a worse overall survival (OS) prognosis. Histone modification, spliceosome, transcription coregulator activity, and nucleocytoplasmic transport were the most significant pathways for ZNF687 differential-related gene enrichment. Chaetocin was found to be a candidate compound and presented a strong affinity to ZNF687. CONCLUSIONS: ZNF687 represents a TKI-resistant and growth-dependent gene for HCC, the overexpression of which indicates poor OS for HCC patients. Additionally, ZNF687 is expected to be a druggable target for overcoming TKI resistance, and chaetocin may be a candidate therapeutic compound for ZNF687.

Global bibliometric mapping of the research trends in artificial intelligence-based digital pathology for lung cancer over the past two decades.

Background and Objective: The rapid development of computer technology has led to a revolutionary transformation in artificial intelligence (AI)-assisted healthcare. The integration of whole-slide imaging technology with AI algorithms has facilitated the development of digital pathology for lung cancer (LC). However, there is a lack of comprehensive scientometric analysis in this field. Methods: A bibliometric analysis was conducted on 197 publications related to digital pathology in LC from 502 institutions across 39 countries, published in 97 academic journals in the Web of Science Core Collection between 2004 and 2023. Results: Our analysis has identified the United States and China as the primary research nations in the field of digital pathology in LC. However, it is important to note that the current research primarily consists of independent studies among countries, emphasizing the necessity of strengthening academic collaboration and data sharing between nations. The current focus and challenge of research related to digital pathology in LC lie in enhancing the accuracy of classification and prediction through improved deep learning algorithms. The integration of multi-omics studies presents a promising future research direction. Additionally, researchers are increasingly exploring the application of digital pathology in immunotherapy for LC patients. Conclusions: In conclusion, this study provides a comprehensive knowledge framework for digital pathology in LC, highlighting research trends, hotspots, and gaps in this field. It also provides a theoretical basis for the application of AI in clinical decision-making for LC patients.

Expression, potential biological behaviour and clinical significance of MCM3 in pancreatic adenocarcinoma: a comprehensive study integrating high throughput sequencing, CRISPR screening and in-house immunohistochemistry.

BACKGROUND: Minichromosome maintenance complex component 3 (MCM3) plays a key role in various tumours. However, it remains largely unknown what the specific role and clinical significance of MCM3 in pancreatic adenocarcinoma (PAAD) are. MATERIALS AND METHODS: We integrated high-throughput data from PAAD worldwide to analyse the expression level of MCM3 mRNA. We used immunohistochemistry to analyse MCM3 protein expression levels in 145 cases in the PAAD group and 29 cases in the non-PAAD group. We also mainly analysed the necessity of MCM3 for PAAD growth based on CRISPR screen data. In addition, we used enrichment analysis and protein-protein interaction networks to explore the molecular mechanism of MCM3 in PAAD. We also analysed the correlation between MCM3 expression, components of the immune microenvironment in PAAD tissue and clinical prognosis. RESULTS: In PAAD, we observed for the first time that MCM3 was significantly highly expressed at both the mRNA (SMD = 0.67, 95% CI: 0.38 ∼ 0.96) and the protein level (p < 0.05). The mRNA (AUC = 0.78, 95% CI: 0.74 ∼ 0.81; sensitivity = 0.66, 95% CI: 0.55 ∼ 0.76; specificity = 0.76, 95% CI: 0.67 ∼ 0.84) and protein (AUC = 0.929) expression levels of MCM3 had a good ability to distinguish between PAAD and non-PAAD tissue. There was heterogeneity reflected by the differential expression of MCM3 protein in PAAD cells. MCM3 played an essential role in PAAD growth, through abnormal DNA replication, p53 signalling and cell cycle checkpoints. PAAD with high MCM3 expression was sensitive to c-75, brivanib, flavopiridol and VNLG/124 drugs, with stable molecular docking models. CONCLUSION: MCM3 is likely to be a critical element in promoting the initiation and growth of PAAD. Flavopiridol may exert its anti-PAAD effect through the interaction between MCM3, classic CDK1 targets in the cell cycle checkpoint and p53 pathway as well as related molecules in other pathways.

MCM3 could potentially play a crucial role in promoting the onset and growth of PAAD.There is heterogeneity reflected by the differential expression of MCM3 protein in PAAD cells.The interplay between MCM3, well-established CDK1 targets in the cell cycle checkpoint and p53 pathway, along with relevant molecules in other pathways, may mediate the anti-pancreatic adenocarcinoma (PAAD) effect of flavopiridol.

Bibliometric study of the application of the chicken embryo chorioallantoic membrane model in cancer research: the top 100 most cited articles.

The chicken embryo chorioallantoic membrane (CAM) model has played a crucial role in various aspects of cancer research. The purpose of this study is to help researchers clarify the research direction and prospects of the CAM model. A bibliometric analysis was conducted on the top 100 most cited articles on use of the CAM model in tumour research, retrieved from the Web of Science Core Collection database. Tools such as Bibliometrix, VOSviewer, CiteSpace and Excel were utilized for the visualization network analysis. The 100 articles analysed were mainly from the USA, China and European countries such as Germany and France. Tumour research involving CAM model experiments demonstrated reliability and scientific rigor (average citation count = 156.2). The analysis of keywords, topics and subject areas revealed that the applications of this model ranged from the biological characteristics of tumours to molecular mechanisms and signaling pathways, to recent developments in nanotechnology and clinical applications. Additionally, nude mouse experiments have been more frequently performed in recent years. We conclude that the CAM model is efficient, simple and cost-effective, and has irreplaceable value in various aspects of cancer research. In the future, the CAM model can further contribute to nanotechnology research.

LSPR-enhanced photoresponsive antibacterial efficiency of Bi/MoS2-loaded fibrin gel for management of diabetic wounds.

Chronic diabetic wounds present formidable challenges, marked by uncontrolled bacterial infections, prolonged inflammation, and impaired angiogenesis. The evolving landscape of photo-responsive antibacterial therapy holds great promise in addressing these multifaceted issues, with a particular focus on leveraging the distinctive properties of 2D heterojunction materials. In this investigation, we engineered composite sprayed hydrogels, seamlessly integrating Bi/MoS2 nano-heterojunctions. Capitalizing on the synergistic interplay between photocatalytic antibacterial and photothermal antibacterial mechanisms, the Bi/MoS2 heterojunction, guided by its localized surface plasmon resonance, demonstrated outstanding antibacterial efficacy within a mere 10-minute exposure to 808 nm near-infrared light. This accelerated sterilization both in vitro and in vivo, consequently expediting wound healing. The sprayed composite gel not only furnishes protective shielding for skin tissues but also fosters endothelial cell proliferation, vascularization, and angiogenesis. This safe and ultrafast sterilizing hydrogel presents immense potential for application in antimicrobial dressings, thereby offering a promising avenue for diabetic wound healing.

Construction of a panoramic mRNA map of adult noncystic fibrosis bronchiectasis and a preliminary study of the underlying molecular mechanisms.

BACKGROUND: The pathogenesis of noncystic fibrosis bronchiectasis in adults is complex, and the relevant molecular mechanisms remain unclear. In this study, we constructed a panoramic map of bronchiectasis mRNA, explored the potential molecular mechanisms, and identified potential therapeutic targets, thus providing a new clinical perspective for the preventive management of bronchiectasis and its acute exacerbation. METHODS: The mRNA profiles of peripheral blood and bronchiectasis tissues were obtained through transcriptome sequencing and public databases, and bioinformatics methods were used to screen for differentially expressed genes (DEGs). The DEGs were then subjected to biological function and pathway analyses. Some DEGs were validated using a real-time quantitative polymerase chain reaction (RT-qPCR) in peripheral blood. Spearman's correlation analysis was used to analyse the correlation between DEGs and clinical indicators. RESULTS: Based on transcriptome sequencing and public databases, the mRNA profile of bronchiectasis was determined. DEGs were obtained from the peripheral blood sequencing dataset (985 DEGs), tissue sequencing dataset (2919 DEGs), and GSE97258 dataset (1083 DEGs). Bioinformatics analysis showed that upregulated DEGs had enriched neutrophil-related pathways, and downregulated DEGs had enriched ribosome-related pathways. RT-qPCR testing confirmed the upregulated expression of VCAN, SESTD1, SLC12A1, CD177, IFI44L, SIGLEC1, and RSAD2 in bronchiectasis. These genes were related to many clinical parameters, such as neutrophils, C-reactive protein, and procalcitonin (P < 0.05). CONCLUSIONS: Transcriptomic methods were used to construct a panoramic map of bronchiectasis mRNA expression. The findings showed that neutrophil activation, chronic inflammation, immune regulation, impaired ribosomal function, oxidative phosphorylation, and energy metabolism disorders are important factors in the development of bronchiectasis. VCAN, SESTD1, SLC12A1, CD177, IFI44L, SIGLEC1, and RSAD2 may play important roles in the pathogenesis of bronchiectasis and are potential therapeutic targets.

What enlightenment has the development of lung cancer bone metastasis brought in the last 22 years.

BACKGROUND: Lung cancer bone metastasis (LCBM) is a disease with a poor prognosis, high risk and large patient population. Although considerable scientific output has accumulated on LCBM, problems have emerged, such as confusing research structures. AIM: To organize the research frontiers and body of knowledge of the studies on LCBM from the last 22 years according to their basic research and translation, clinical treatment, and clinical diagnosis to provide a reference for the development of new LCBM clinical and basic research. METHODS: We used tools, including R, VOSviewer and CiteSpace software, to measure and visualize the keywords and other metrics of 1903 articles from the Web of Science Core Collection. We also performed enrichment and protein-protein interaction analyses of gene expression datasets from LCBM cases worldwide. RESULTS: Research on LCBM has received extensive attention from scholars worldwide over the last 20 years. Targeted therapies and immunotherapies have evolved into the mainstream basic and clinical research directions. The basic aspects of drug resistance mechanisms and parathyroid hormone-related protein may provide new ideas for mechanistic study and improvements in LCBM prognosis. The produced molecular map showed that ribosomes and focal adhesion are possible pathways that promote LCBM occurrence. CONCLUSION: Novel therapies for LCBM face animal testing and drug resistance issues. Future focus should centre on advancing clinical therapies and researching drug resistance mechanisms and ribosome-related pathways.

Bibliometric analysis of phosphoglycerate kinase 1 expression in breast cancer and its distinct upregulation in triple-negative breast cancer.

BACKGROUND: Phosphoglycerate kinase 1 (PGK1) has been identified as a possible biomarker for breast cancer (BC) and may play a role in the development and advancement of triple-negative BC (TNBC). AIM: To explore the PGK1 and BC research status and PGK1 expression and mechanism differences among TNBC, non-TNBC, and normal breast tissue. METHODS: PGK1 and BC related literature was downloaded from Web of Science Core Collection Core Collection. Publication counts, key-word frequency, cooperation networks, and theme trends were analyzed. Normal breast, TNBC, and non-TNBC mRNA data were gathered, and differentially expressed genes obtained. Area under the summary receiver operating characteristic curves, sensitivity and specificity of PGK1 expression were determined. Kaplan Meier revealed PGK1's prognostic implication. PGK1 co-expressed genes were explored, and Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Disease Ontology applied. Protein-protein interaction networks were constructed. Hub genes identified. RESULTS: PGK1 and BC related publications have surged since 2020, with China leading the way. The most frequent keyword was "Expression". Collaborative networks were found among co-citations, countries, institutions, and authors. PGK1 expression and BC progression were research hotspots, and PGK1 expression and BC survival were research frontiers. In 16 TNBC vs non-cancerous breast and 15 TNBC vs non-TNBC datasets, PGK1 mRNA levels were higher in 1159 TNBC than 1205 non-cancerous breast cases [standardized mean differences (SMD): 0.85, 95% confidence interval (95%CI): 0.54-1.16, I² = 86%, P < 0.001]. PGK1 expression was higher in 1520 TNBC than 7072 non-TNBC cases (SMD: 0.25, 95%CI: 0.03-0.47, I² = 91%, P = 0.02). Recurrence free survival was lower in PGK1-high-expression than PGK1-low-expression group (hazard ratio: 1.282, P = 0.023). PGK1 co-expressed genes were concentrated in ATP metabolic process, HIF-1 signaling, and glycolysis/gluconeogenesis pathways. CONCLUSION: PGK1 expression is a research hotspot and frontier direction in the BC field. PGK1 may play a strong role in promoting cancer in TNBC by mediating metabolism and HIF-1 signaling pathways.

The upregulation and transcriptional regulatory mechanisms of Extra spindle pole bodies like 1 in bladder cancer: An immunohistochemistry and high-throughput screening Evaluation.

Background: This study aimed to explore the expression level and transcriptional regulation mechanism of Extra Spindle Pole Bodies Like 1 (ESPL1) in bladder cancer (BC). Methods: A multicentre database of samples (n = 1391) was assayed for ESPL1 mRNA expression in BC and validated at the protein level by immunohistochemical (IHC) staining of in-house samples (n = 202). Single-cell sequencing (scRNA-seq) analysis and enrichment analysis explored ESPL1 distribution and their accompanying molecular mechanisms. ATAC-seq, ChIP-seq and Hi-C data from multiple platforms were used to investigate ESPL1 upstream transcription factors (TFs) and potential epigenetic regulatory mechanisms. Immune-related analysis, drug sensitivity and molecular docking of ESPL1 were also calculated. Furthermore, upstream microRNAs and the binding sites of ESPL1 were predicted. The expression level and early screening efficacy of miR-299-5p in blood (n = 6625) and tissues (n = 537) were examined. Results: ESPL1 was significantly overexpressed at the mRNA level (p < 0.05, SMD = 0.75; 95 % CI = 0.09, 1.40), and IHC staining of in-house samples verified this finding (p < 0.0001). ESPL1 was predominantly distributed in BC epithelial cells. Coexpressed genes of ESPL1 were enriched in cell cycle-related signalling pathways, and ESPL1 might be involved in the communication between epithelial and residual cells in the Hippo, ErbB, PI3K-Akt and Ras signalling pathways. Three TFs (H2AZ, IRF5 and HIF1A) were detected upstream of ESPL1 and presence of promoter-super enhancer and promoter-typical enhancer loops. ESPL1 expression was correlated with various immune cell infiltration levels. ESPL1 expression might promote BC growth and affect the sensitivity and therapeutic efficacy of paclitaxel and gemcitabine in BC patients. As an upstream regulator of ESPL1, miR-299-5p expression was downregulated in both the blood and tissues, possessing great potential for early screening. Conclusions: ESPL1 expression was upregulated in BC and was mainly distributed in epithelial cells. Elevated ESPL1 expression was associated with TFs at the upstream transcription start site (TSS) and distant chromatin loops of regulatory elements. ESPL1 might be an immune-related predictive and diagnostic marker for BC, and the overexpression of ESPL1 played a cancer-promoting role and affected BC patients' sensitivity to drug therapy. miR-299-5p was downregulated in BC blood and tissues and was also expected to be a novel marker for early screening.

Clinical significance and potential pathogenesis of VCAN in adult non-cystic fibrosis bronchiectasis: a retrospective study.

BACKGROUND: The pathogenesis of adult non-cystic fibrosis (CF) bronchiectasis is complex, and the relevant molecular mechanism remains ambiguous. Versican (VCAN) is a key factor in inflammation through interactions with adhesion molecules. This study constructs a stable panoramic map of mRNA, reveals the possible pathogenesis of bronchiectasis, and provides new ideas and methods for bronchiectasis. METHODS: Peripheral blood and tissue gene expression data from patients with bronchiectasis and normal control were selected by bioinformatics analysis. The expression of VCAN in peripheral blood and bronchial tissues of bronchiectasis were obtained by transcriptome sequencing. The protein expression levels of VCAN in serums were verified by the enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of VCAN in co-culture of Pseudomonas aeruginosa and bronchial epithelial cells were verified by real-time quantitative polymerase chain reaction (RT-qPCR). In addition, the biological function of VCAN was detected by the transwell assay. RESULTS: The expression of VCAN was upregulated in the bronchiectasis group by sequencing analysis (P < 0.001). The expression of VCAN in the bronchial epithelial cell line BEAS-2B was increased in P. aeruginosa (P.a), which was co-cultured with BEAS-2B cells (P < 0.05). The concentration of VCAN protein in the serum of patients with bronchiectasis was higher than that in the normal control group (P < 0.05). Transwell experiments showed that exogenous VCAN protein induced the migration of neutrophils (P < 0.0001). CONCLUSIONS: Our findings indicate that VCAN may be involved in the development of bronchiectasis by increasing the migration of neutrophils and play an important role in bronchial pathogenesis.

Overexpressed KCNK1 regulates potassium channels affecting molecular mechanisms and biological pathways in bladder cancer.

BACKGROUND: This study aimed to explore the expression, molecular mechanism and its biological function of potassium two pore domain channel subfamily K member 1 (KCNK1) in bladder cancer (BC). METHODS: We integrated large numbers of external samples (n = 1486) to assess KCNK1 mRNA expression levels and collected in-house samples (n = 245) for immunohistochemistry (IHC) experiments to validate at the KCNK1 protein level. Single-cell RNA sequencing (scRNA-seq) analysis was performed to further assess KCNK1 expression and cellular communication. The transcriptional regulatory mechanisms of KCNK1 expression were explored by ChIP-seq, ATAC-seq and ChIA-PET data. Highly expressed co-expressed genes (HECEGs) of KCNK1 were used to explore potential signalling pathways. Furthermore, the immunoassay, clinical significance and molecular docking of KCNK1 were calculated. RESULTS: KCNK1 mRNA was significantly overexpressed in BC (SMD = 0.58, 95% CI [0.05; 1.11]), validated at the protein level (p < 0.0001). Upregulated KCNK1 mRNA exhibited highly distinguishing ability between BC and control samples (AUC = 0.82 [0.78-0.85]). Further, scRNA-seq analysis revealed that KCNK1 expression was predominantly clustered in BC epithelial cells and tended to increase with cellular differentiation. BC epithelial cells were involved in cellular communication mainly through the MK signalling pathway. Secondly, the KCNK1 transcription start site (TSS) showed promoter-enhancer interactions in three-dimensional space, while being transcriptionally regulated by GRHL2 and FOXA1. Most of the KCNK1 HECEGs were enriched in cell cycle-related signalling pathways. KCNK1 was mainly involved in cellular metabolism-related pathways and regulated cell membrane potassium channel activity. KCNK1 expression was associated with the level of infiltration of various immune cells. Immunotherapy and chemotherapy (docetaxel, paclitaxel and vinblastine) were more effective in BC patients in the high KCNK1 expression group. KCNK1 expression correlated with age, pathology grade and pathologic_M in BC patients. CONCLUSIONS: KCNK1 was significantly overexpressed in BC. A complex and sophisticated three-dimensional spatial transcriptional regulatory network existed in the KCNK1 TSS and promoted the upregulated of KCNK1 expression. The high expression of KCNK1 might be involved in the cell cycle, cellular metabolism, and tumour microenvironment through the regulation of potassium channels, and ultimately contributed to the deterioration of BC.

Clinicopathological role of Cyclin A2 in uterine corpus endometrial carcinoma: Integration of tissue microarrays and ScRNA-Seq.

BACKGROUND: The comprehensive expression level and potential molecular role of Cyclin A2 (CCNA2) in uterine corpus endometrial carcinoma (UCEC) remains undiscovered. METHODS: UCEC and normal endometrium tissues from in-house and public databases were collected for investigating protein and messenger RNA expression of CCNA2. The transcription factors of CCNA2 were identified by the Cistrome database. The prognostic significance of CCNA2 in UCEC was evaluated through univariate and multivariate Cox regression as well as Kaplan-Meier curve analysis. Single-cell RNA-sequencing (scRNA-seq) analysis was performed to explore cell types in UCEC, and the AUCell algorithm was used to investigate the activity of CCNA2 in different cell types. RESULTS: A total of 32 in-house UCEC and 30 normal endometrial tissues as well as 720 UCEC and 165 control samples from public databases were eligible and collected. Integrated calculation showed that the CCNA2 expression was up-regulated in the UCEC tissues (SMD = 2.43, 95% confidence interval 2.23∼2.64). E2F1 and FOXM1 were identified as transcription factors due to the presence of binding peaks on transcription site of CCNA2. CCNA2 predicted worse prognosis in UCEC. However, CCNA2 was not an independent prognostic factor in UCEC. The scRNA-seq analysis disclosed five cell types: B cells, T cells, monocytes, natural killer cells, and epithelial cells in UCEC. The expression of CCNA2 was mainly located in B cells and T cells. Moreover, CCNA2 was active in T cells and B cells using the AUCell algorithm. CONCLUSION: CCNA2 was up-regulated and mainly located in T cells and B cells in UCEC. Overexpression of CCNA2 predicted unfavorable prognosis of UCEC.

A novel prognostic signature of coagulation-related genes leveraged by machine learning algorithms for lung squamous cell carcinoma.

Coagulation-related genes (CRGs) have been demonstrated to be essential for the development of certain tumors; however, little is known about CRGs in lung squamous cell carcinoma (LUSC). In this study, we adopted CRGs to construct a coagulation-related gene prognostic signature (CRGPS) using machine learning algorithms. Using a set of 92 machine learning integrated algorithms, the CRGPS was determined to be the optimal prognostic signature (median C-index = 0.600) for predicting the prognosis of an LUSC patient. The CRGPS was not only superior to traditional clinical parameters (e.g., T stage, age, and gender) and its commutative genes but also outperformed 19 preexisting prognostic signatures for LUSC on predictive accuracy. The CRGPS score was positively correlated with poor prognoses in patients with LUSC (hazard ratio > 1, p < 0.05), indicating its suitability as a prognostic marker for this disease. The CRGPS was observed to be inversely correlated with the degree of infiltration of natural killer cells. For some tumors, patients with lower CRGPS scores are more likely to experience enhanced immunotherapy effects (area under the curve = 0.70), which implies that the CRGPS can potentially predict immunotherapy efficacy. A high CRGPS score is predictive of an LUSC patient being sensitive to several drugs. Collectively, these findings indicate that the CRGPS may be a reliable indicator of the prognoses of patients with LUSC and may be useful for the clinical management of such patients.

TM9SF1 promotes bladder cancer cell growth and infiltration.

BACKGROUND: Bladder cancer (BC) is the most common urological tumor. It has a high recurrence rate, displays tutor heterogeneity, and resists chemotherapy. Furthermore, the long-term survival rate of BC patients has remained unchanged for decades, which seriously affects the quality of patient survival. To improve the survival rate and prognosis of BC patients, it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention. Transmembrane 9 superfamily member 1 (TM9SF1), also known as MP70 and HMP70, is a member of a family of nine transmembrane superfamily proteins, which was first identified in 1997. TM9SF1 can be expressed in BC, but its biological function and mechanism in BC are not clear. AIM: To investigate the biological function and mechanism of TM9SF1 in BC. METHODS: Cells at 60%-80% confluence were transfected with lentiviral vectors for 48-72 h to achieve stable TM9SF1 overexpression or silencing in three BC cell lines (5637, T24, and UM-UC-3). The effect of TM9SF1 on the biological behavior of BC cells was then investigated through CCK8, wound-healing assay, transwell assay, and flow cytometry. RESULTS: Overexpression of TM9SF1 increased the in vitro proliferation, migration, and invasion of BC cells by promoting the entry of BC cells into the G2/M phase. Silencing of TM9SF1 inhibited in vitro proliferation, migration, and invasion of BC cells and blocked BC cells in the G1 phase. CONCLUSION: TM9SF1 may be an oncogene in BC.

Hemorrhoidal disease and its genetic association with depression, bipolar disorder, anxiety disorders, and schizophrenia: a bidirectional mendelian randomization study.

BACKGROUND: Hemorrhoids and psychiatric disorders exhibit high prevalence rates and a tendency for relapse in epidemiological studies. Despite this, limited research has explored their correlation, and these studies are often subject to reverse causality and residual confounding. We conducted a Mendelian randomization (MR) analysis to comprehensively investigate the association between several mental illnesses and hemorrhoidal disease. METHODS: Genetic associations for four psychiatric disorders and hemorrhoidal disease were obtained from large consortia, the FinnGen study, and the UK Biobank. Genetic variants associated with depression, bipolar disorder, anxiety disorders, schizophrenia, and hemorrhoidal disease at the genome-wide significance level were selected as instrumental variables. Screening for potential confounders in genetic instrumental variables using PhenoScanner V2. Bidirectional MR estimates were employed to assess the effects of four psychiatric disorders on hemorrhoidal disease. RESULTS: Our analysis revealed a significant association between genetically predicted depression and the risk of hemorrhoidal disease (IVW, OR=1.20,95% CI=1.09 to 1.33, P <0.001). We found no evidence of associations between bipolar disorder, anxiety disorders, schizophrenia, and hemorrhoidal disease. Inverse MR analysis provided evidence for a significant association between genetically predicted hemorrhoidal disease and depression (IVW, OR=1.07,95% CI=1.04 to 1.11, P <0.001). CONCLUSIONS: This study offers MR evidence supporting a bidirectional causal relationship between depression and hemorrhoidal disease.

Clinical Significance of Upregulation of EZH1 Expression in Hepatocellular Carcinoma Tissues.

BACKGROUND AND AIMS: The incidence and mortality of hepatocellular carcinoma (HCC) are increasing. It is urgent to develop more effective HCC biomarkers for diagnosis and treatment. This project intends to verify the expression of enhancer of zeste 1 polycomb repressive complex 2 subunit (EZH1) and its mechanism in HCC. METHODS: This study integrates global microarray and high-throughput sequencing datasets, combined with internal immunohistochemistry, to analyze the expression and prognostic value of EZH1 in HCC. Functional enrichment analysis was conducted to investigate transcriptional targets, which were achieved by intersecting HCC over-expressed genes, EZH1 co-expressed genes and putative transcriptional targets. The relationship between EZH1 and anticancer drugs was detected by drug sensitivity analysis. RESULTS: In this study, 84 datasets from 40 platforms (3,926 HCC samples and 3,428 non-cancerous liver tissues) were included to show the high expression of EZH1 in HCC. Immunohistochemistry with 159 HCC samples and 62 non-HCC samples confirmed the high expression level. HCC patients with high EZH1 expression had worse survival prognoses. Gene ontology and Reactome analysis revealed that metabolism-related pathways, including autophagy, are critical for HCC. Interestingly, as one of the EZH1 potential transcriptional targets, autophagy-related 7 (ATG7) appeared in the above pathways. ATG7 was positively correlated with EZH1, upregulated in HCC, and mediated poor prognosis. Upregulation of EZH1 was found to be in contact with HCC anti-tumor drug resistance. CONCLUSIONS: The upregulation of EZH1 expression can promote the occurrence of HCC and lead to poor clinical progression and drug resistance; these effects may be mediated by regulating ATG7.

The 'whole landscape' of research on systemic sclerosis over the past 73 years.

OBJECTIVE: This study aimed to analyse existing research on systemic sclerosis (SSc) conducted over the past 73 years to develop an essential reference for a comprehensive and objective understanding of this field of inquiry. METHODS: Using the Web of Science Core Collection, PubMed, and Scopus databases as data sources for the bibliometric analysis, we searched for published literature related to SSc over the past 73 years. The Bibliometrix package was used to analyse key bibliometric indicators, such as annual publication volume, countries, journals, author contributions, and research hotspots. RESULTS: From 1970 to 2022, the number of SSc articles steadily increased, reaching its peak in 2020-2022, with approximately 1200 papers published in each of these three years. Matucci-Cerinic et al.'s team published the most articles (425). The United States (11,282), Italy (7027), and France (5226) were the most predominant contexts. The most influential scholars in the field were Denton, Leroy, Steen, and Khanna, with H-indices of 86, 84, and 83, respectively. Arthritis and Rheumatism was the most influential journal in this field (H-index 142). High-frequency keywords in the SSc field included fibrosis (738), inflammation (242), vasculopathy (145), fibroblasts (120), and autoantibodies (118) with respect to pathogenesis, and interstitial lung disease (ILD, 708), pulmonary arterial hypertension (PAH, 696), and Raynaud's phenomenon (326) with regards to clinical manifestations. CONCLUSION: In the past three years, SSc research has entered a period of rapid development, mainly driven by research institutions in Europe and the United States. The most influential journal has been Arthritis and Rheumatism, and autoimmune aspects, vasculopathy, fibrogenesis, PAH, and ILD remain the focus of current research and indicate trends in future research.

Differential expression of miRNA-769-5p and Smad2 in patients with or without oral cGVHD.

BACKGROUND: Oral chronic graft-versus-host disease (cGVHD) impacts quality of life of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, its precise pathogenesis remains unknown, with potential associations with differential microRNA (miRNA) expression and the TGF-â/Smad signaling pathway. OBJECTIVES: This study aims to explore miRNA expression profiles in the peripheral blood of oral cGVHD patients, focusing on miRNA-769-5p and its relationship with Smad2. MATERIAL AND METHODS: Peripheral venous blood samples were collected for RNA extraction from 8 patients with oral cGVHD, 8 patients without cGVHD and 8 participants from the healthy control group. The miRNA library was constructed using the Illumina Hiseq 2500 platform. We focused on identifying miRNAs associated with the TGF-â/Smad signaling pathway and subsequently conducted validation experiments. The oral cGVHD and without cGVHD groups were each expanded to include 15 individuals. Peripheral blood samples were subjected to polymerase chain reaction (PCR) analysis to assess miRNA levels and to evaluate Smad2 mRNA levels in peripheral blood mononuclear cells (PBMC). Additionally, enzyme-linked immunosorbent assay (ELISA) was conducted to determine the Smad2 protein levels in peripheral blood. RESULTS: The most significantly differentially expressed miRNAs among the 3 groups were miRNA-505-5p and miRNA-769-5p. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated an enrichment of the target genes of miRNA-769-5p in the TGF-â signaling pathway. It was observed that miRNA-769-5p expression was higher in patients without oral cGVHD in comparison to those with oral cGVHD. Receiver operating characteristic (ROC) analysis demonstrated that miRNA-769-5p holds diagnostic value for oral cGVHD. As a target of miRNA-769-5p, Smad2 mRNA exhibited a negative correlation with it. Moreover, both Smad2 mRNA and protein levels were higher in patients with oral cGVHD as opposed to those without cGVHD. CONCLUSIONS: Differential expression of miRNAs, particularly the downregulation of miRNA-769-5p, may influence the development of oral cGVHD by diminishing its inhibitory effect on the TGF-â/Smad signaling pathway through its interaction with Smad2.