Cancer remains a leading cause of global mortality, with incidence and mortality rates rising annually. Atorvastatin, a widely used statin, primarily functions by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in the mevalonate pathway, thereby lowering cholesterol. Accumulating preclinical and clinical evidence suggests that ATV possesses significant anticancer properties beyond its lipid-lowering effects, positioning it as a promising candidate for adjunctive cancer therapy. The anticancer efficacy of ATV stems fundamentally from its disruption of the mevalonate pathway, which impedes the critical isoprenylation of small GTPases (e.g., Ras, Rho). This inhibition cascades into multifaceted antitumor activities, including the induction of apoptosis and autophagy, dysregulation of the cell cycle, suppression of proliferation, migration, and invasion. ATV further modulates key oncogenic signaling pathways and exhibits potent anti-inflammatory and antioxidant effects within the tumor microenvironment. Crucially, evidence demonstrates that integrating ATV into multimodality regimens—such as alongside immune checkpoint inhibitors and metabolic modulators—significantly improves survival outcomes in patients, substantiating its clinical translational potential. However, a comprehensive and systematic evaluation of its pleiotropic anticancer mechanisms and therapeutic potential is lacking. This review aims to fill this gap by systematically summarizing the efficacy and molecular mechanisms of ATV across various malignancies, alongside its cytoprotective effects on normal tissues. The challenges and future directions for its clinical translation in oncology are also critically discussed.

Major Depressive Disorder (MDD) is a highly disabling psychiatric condition. The diagnostic and therapeutic challenges associated with MDD stem from an incomplete understanding of its pathogenesis, particularly the complex cellular interactions and the influence of peripheral factors on the central nervous system (CNS). Current metagenomics and single-cell studies are largely confined to individual omics layers. This study integrated multi-cohort gut metagenomic data with cortical single-nucleus transcriptomics to elucidate gut-brain axis regulatory mechanisms in depression. We observed significant enrichment of Streptococcus in MDD patients, accompanied by reprogramming of microbial pathways related to neural signaling and lipid metabolism. Cortical analysis revealed reduced astrocyte proportions with functional impairment, and increased proportions of L5/6_THEMIS_1 and ID2_PLP1 neuron subtypes exhibiting metabolic stress signatures. Diagnostic models based on microbial signatures and astrocyte markers achieved AUCs of 0.914 and 0.854, respectively. Cross-omics correlation analysis demonstrated a significant association between microbial and cortical pathways (R = 0.796) and identified five core functional modules. This study constructs a molecular network of gut-brain axis regulation in MDD, revealing multi-dimensional functional coupling between gut microbiota and cortical cells, and providing evidence for how peripheral microbes influence central cellular function.

BACKGROUND:The neurokinin-B (NKB)/neurokinin-3-receptor (NK3R) pathway is involved in the inflammatory response. However, its role in the disruption of intestine mucosal barrier during mechanical intestinal obstruction (IO) remains unknown. METHODS:We collected serum samples from 30 mechanical IO patients and 30 healthy volunteers and measured the serum levels of NKB, lipopolysaccharide (LPS), diamine oxidase (DAO), and D‑lactate (D‑LA) by using ELISA. We subsequently used a mechanical IO mice model and intraperitoneally injected the mice with NKB (Senktide) and NK3R antagonist (NK3Ra). We used the ELISA to measure the tumor necrosis factor (TNF)-α, interleukin (IL)-6, LPS, DAO, and D-LA serum concentrations in the mice. Hematoxylin-eosin (H&E) staining and transmission electron microscopy (TEM) were used to observe structural changes in the intestinal mucosa. Immunohistochemistry was used to detect the expression of claudin-1, occludin and ZO-1 in intestinal tissues. RESULTS:Serum NKB (75.36 ± 28.67 pg/mL vs. 44.95 ± 16.92 pg/mL) and LPS (7.38 ± 3.63 μg/mL vs. 4.50 ± 2.94 μg/mL) levels were higher in mechanical IO patients than in control people (P < 0.05). We found a positive correlation between serum NKB and LPS levels in mechanical IO patients. The serum LPS concentration in the IO+NKB mice was greater than that in the IO mice (P = 0.001). After the use of NK3Ra, the serum LPS, DAO and D-LA levels decreased (P < 0.05). H&E staining indicated that the intestinal mucosal epithelial structure was severely damaged, including lamina propria hemorrhage, atrophied villi, and inflammatory cell infiltration in IO+NKB mice. TEM revealed that the junctional complexes between epithelial cells were disrupted and absent in the IO+NKB mice. Compared with those in the IO mice, the expression levels of claudin-1 and occludin in intestinal tissues were lower in the IO+NKB mice. However, the intraperitoneal injection of NK3Ra attenuated the damage to tight junction proteins and the intestinal mucosal structure caused by NKB. Additionally, we observed that the serum IL-6 and TNF-α levels in the IO+NK3Ra mice were lower than those in the IO mice (P < 0.05). CONCLUSIONS:NKB might increase the levels of serum IL-6 and TNF-α by acting on the NK3 receptor, promoting intestinal inflammation, and subsequently destroying the intestinal mucosal barrier during mechanical IO.

Purpose:Microbial communities have emerged as crucial regulators in the initiation and progression of thyroid cancer. However, most studies focus on single microbial sources, and the interplay between microbes across different ecological niches and their impact on thyroid carcinogenesis are largely unknown. Patients and Methods:In this study, we collected tissue, oral, and fecal samples from 32 patients with benign thyroid nodules (BTN) and 32 patients with papillary thyroid carcinoma (PTC). The oral and fecal samples were subjected to 16S rRNA sequencing, while the tissue samples were analyzed using 5R 16S sequencing to comprehensively characterize the microbial communities. Results:Clustering analysis using the Dirichlet Multinomial Mixture model with Laplace approximation identified two distinct oral microbial community types (O_1 and O_2) and three fecal types (F_1, F_2, and F_3). Microbial diversity patterns in thyroid tissues mirrored those observed in oral and fecal samples, suggesting potential microbial translocation or systemic interactions. Inflammatory markers were significantly elevated in PTC patients relative to BTN controls. Notably, the genus Veillonella, a potential anti-tumor biomarker, was significantly reduced in PTC samples across niches. Conclusion:This study highlights the pivotal role of oral and intestinal microbiota in PTC development, emphasizing the interplay between microbial composition, inflammatory processes, and immune regulation in tumor progression. The discovery of Veillonella as a potential anti-tumor microbe, along with evidence of microbial translocation, opens new possibilities for targeted therapeutic strategies.

IntroductionThe primary clinical challenge associated with follicular thyroid carcinoma (FTC) lies in accurately diagnosing the condition, particularly in distinguishing it with follicular thyroid adenoma (FTA) due to their overlapping cytomorphological features and sonographic characteristics.MethodsWhole exome sequencing (WES) techniques and Gene Expression Omnibus (GEO) database were utilized to analyze genomic difference between FTC and FTA, with a specific focus on immune-related genes. The hub genes were subjected to enrichment analysis, immune infiltration analysis, protein-protein interaction (PPI) analysis, and receiver operating characteristic (ROC) curve analysis. Then utilized quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) to validate the expression levels of PMAIP1 and PDGFRL at the cellular and tissue levels.ResultsThe findings of WES and bioinformatics analysis indicated that PMAIP1 and PDGFRL were potential mutated immune-related genes in FTC, in comparison to FTA, the expression of PMAIP1 is up-regulated in FTC while PDGFRL is down-regulated, demonstrating promising diagnostic efficacy. Enrichment analysis and immune infiltration analysis suggested that PMAIP1 and PDGFRL may serve as potential therapeutic targets for FTC. The results of the validation at both cellular and tissue levels indicated an up-regulation of PMAIP1 and a down-regulation of PDGFRL in FTC, consistent with the results from bioinformatics analysis. DiscussionIn conclusion, it is the first research to revealed PMAIP1 and PDGFRL as potential novel immunodiagnostic markers for FTC, shedding light on their potential biological significance in this context, and offering potential valuable clinical applications.

Colorectal cancer (CRC) is a prevalent digestive system malignancy accompanied by peritoneal metastasis occurring in 7% of cases. Methyltransferase-like 3 (METTL3) promoted the progression of CRC whereas its function in peritoneal metastasis was incompletely understood. Here, we found that METTL3 was upregulated in peritoneal metastasis tissues of CRC patients compared with CRC tissues. By sequencing the mRNA of above tissues, we discovered that METTL3-mediated N6-methyladenosine (m6A) modification regulated the downstream target neurexin-3 (NRXN3). NRXN3 promoted CRC peritoneal metastasis in vivo. Mechanically, we further verified the specific methylation sites of NRXN3 mRNA modified by METTL3. Functional cellular assays demonstrated METTL3-mediated upstream regulation of NRXN3. We also demonstrated that YTHDC1 is necessary for the METTL3-mediated stabilization of NRXN3 mRNA. Taken together, this study established a METTL3-YTHDC1-NRXN3 m6A modification-dependent regulation system in CRC peritoneal metastasis, suggesting potential candidates for peritoneal metastasis treatment.

Objective:To explore the correlation between chromosome 8 open reading frame 76 (C8orf76) and cyclin-dependent kinase 4 (CDK4) and the potential predictive effect of C8orf76 and CDK4 on the prognosis of colorectal cancer (CRC). Methods:We constructed a protein-protein interaction network of C8orf76-related genes and analyzed the prognostic signatures of C8orf76 and CDK4. Clinicopathological features of C8orf76 and CDK4 were visualized using a nomogram. Results:C8orf76 and CDK4 levels were positively correlated in two independent human CRC cohorts ( n = 83 and n = 597). A consistent positive correlation was observed between C8orf76 and CDK4 expression in the CRC cell lines. The nomogram included prognostic genes (C8orf76 and CDK4) and pathological N and M stages. The concordance index (C-index) in our cohort was 0.776, which suggests that the ability of the indicators to predict the overall survival of patients with CRC in our cohort was strong. Conclusion:We found that C8orf76 was positively correlated with CDK4 in both the cohorts as well as in CRC cell lines. Therefore, C8orf76 and CDK4 can be used as potential biomarkers to predict the prognosis of CRC.

Background:Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death worldwide. The accurate preoperative prediction of lymph node (LN) status is crucial for reducing NSCLC mortality rates and formulating treatment strategies. This study aimed to develop and validate a nomogram for the individualized prediction of lymph node metastasis (LNM) risk in NSCLC patients, thereby guiding therapeutic decision making. Methods:The complete clinical, computed tomography (CT) imaging, and pathological data of patients with pathologically confirmed NSCLC at three independent tertiary medical centers from January 2014 to October 2023 were retrospectively collected and analyzed. In total, 2,725 patients were enrolled from Centers 1 and 2, and 112 patients were enrolled from center 3. The patients were randomly divided into training and test datasets at an 8:2 ratio. A clinical CT imaging predictive model was established by binary logistic regression analysis, and a corresponding nomogram chart was constructed. The predictive ability, discriminative ability, accuracy, and clinical benefit of the model were evaluated by receiver operating characteristic (ROC) curve, calibration curve, decision curve, and clinical impact curve (CIC) analyses. Results:Mixed ground-glass opacity (mGGO), obstructive inflammation, emphysema or bullae, a short diameter (SD), and heterogeneous ventilation or perfusion (HVP) were identified as independent risk factors for LN positivity in NSCLC. The model had an area under the curve (AUC) of 0.893, an accuracy of 76.8%, a sensitivity of 91.6%, and a specificity of 74.2% on the training dataset. While it had an AUC of 0.907, an accuracy of 86.2%, a sensitivity of 89.3%, and a specificity of 80.9% on the test dataset. Conclusions:We developed and validated a robust clinical CT imaging nomogram model that effectively predicts LN positivity in NSCLC.

Immune checkpoint blockade (ICB) therapy demonstrated limited efficacy in colorectal cancer (CRC), and identification of intrinsic factors modulating immune suppression in CRC is an unmet need. Here, we revealed that Chromosome 8 open reading frame 76 (C8orf76) drives immunosuppression and is a molecular target to boost ICB therapy in CRC. C8orf76 is upregulated in primary CRCs compared to adjacent normal tissues in 2 independent CRC cohorts and its expression predicts poor patient survival. Intestine-specific C8orf76 knockin in mice exacerbated AOM/DSS-induced CRC, accompanied by increased intratumoral myeloid-derived suppressor cells (MDSCs) but reduced IFN-γ+ and granzyme B+ CD8+ T cells, inferring that C8orf76 promotes immunosuppression in CRC. Consistently, genetic depletion of C8orf76 augmented antitumour immunity in CT26 (MSS-CRC) and MC38 (MSI-H-CRC) allograft models. Integrated RNA-seq and ChIP-seq revealed that C8orf76 functions as a transcription factor to drive NDST1 expression, which activates the PI3K-Akt-NF-κB signaling cascade. Activated NF-κB in turn promotes the expression and secretion of CXCL1, a major chemoattractant for MDSCs. Consequently, C8orf76-induced CXCL1 mediates the recruitment of MDSCs via CXCR2 to antagonize functional CD8+ T cells in tumor immune microenvironment of CRC. Confirming this, targeting NDST1 or CXCR2 could reverse C8orf76 induced immunosuppression in vivo. Finally, we tested the translational value of C8orf76 using genetic ablation or vesicle-like nanoparticles (VNPs)-encapsulated C8orf76-siRNA. In line with our hypothesis, we demonstrated that targeting C8orf76 by genetic ablation or VNPs-encapsulated C8orf76-siRNA potentiated the anti-PD1 efficacy in both MSI-H and MSS CRC models. In summary, C8orf76 drives immunosuppression through a NDST1-CXCL1/CXCR2 axis, and targeting C8orf76 is a promising approach to boost ICB therapy efficacy in CRC. Hongyan Gou, Shang Guo, Xiaohong Wang, Xia Jiang, Chi Chun Wong, Huarong Chen, Chunxian Wei, Lingxue Shi, Zengren Zhao, Jun Yu. C8orf76 promotes colorectal tumorigenesis by promoting an immunosuppressive microenvironment and is a therapeutic target for boosting anti-PD-1 efficacy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB132.

It has been demonstrated that lncRNA HOXC-AS2 regulates the tumorigenesis and progression of multiple tumors. In present study we explored the biological function of HOXC-AS2 in colorectal cancer and its potential mechanisms. Firstly, we found that the expression of HOXC-AS2 was down-regulated in colorectal cancer tissues than its adjacent normal tissues, and the expression level of HOXC-AS2 was found to show an inversely correlated with tumor size by analyzing the clinicopathological characteristics. HOXC-AS2 knockdown significantly increased its proliferation and colony formation ability in colorectal cancer cells, and conversely, HOXC-AS2 overexpression significantly decreased its proliferation and colony formation ability, suggesting that HOXC-AS2 exerts anti-tumor effect in colorectal cancer. In addition, we found that miR-146b-5p, as a downstream bioactive factor, could be targeting sponged by HOXC-AS2 in colorectal cancer, and the expression of UBE2L6 was regulated by miR-146b-5p. Thus, HOXC-AS2 inhibits the proliferation and colony formation ability in colorectal cancer cells by targeted sponging miR-146b-5p and then regulates UBE2L6.

Abnormal expression of circRNAs has been observed in different types of carcinomas, and they play significant roles in the biology of these cancers. Nevertheless, the clinical relevance and functional mechanisms of the majority of circRNAs implicated in breast cancer progression remain unclear. The primary objective of our investigation is to uncover new circRNAs in breast cancer and elucidate the underlying mechanisms by which they exert their effects. The circRNA expression profile data for breast cancer and RNA-sequencing data were acquired from distinct public databases. Differentially expressed circRNAs and mRNA were identified through fold change filtering. The establishment of the competing endogenous RNAs (ceRNAs) network relied on the interplay between circular RNAs, miRNAs, and mRNAs. The hub genes were identified from the protein-protein interaction (PPI) regulatory network using the CytoHubba plugin in Cytoscape. Moreover, the expression levels and prognostic value of these hub genes in the PPI network were assessed using the GEPIA and Kaplan-Meier plotter databases. Fluorescence in situ hybridization (FISH) was used to identified the expression and intracellular localization of hsa_circ_0059665 by using the tissue microarray. Transwell analysis and CCK-8 analysis were performed to assess the invasion, migration, and proliferation abilities of breast cancer cells. Additionally, we investigated the interactions between hsa_circ_0059665 and miR-602 through various methods, including FISH, RNA-binding protein immunoprecipitation (RIP), and luciferase reporter assay. Rescue experiments were conducted to determine the potential regulatory role of hsa_circ_0059665 in breast cancer progression. A total of 252 differentially expressed circRNAs were identified. Among them, 246 circRNAs were up-regulated, while 6 circRNAs were down-regulated. Based on prediction and screening of circRNA-miRNA and miRNA-mRNA binding sites, we constructed a network consisting of circRNA-miRNA-mRNA interactions. In addition, we constructed a Protein-Protein Interaction (PPI) network and identified six hub genes. Moreover, the expression levels of these six hub genes in breast cancer tissues were found to be significantly lower. Furthermore, the survival analysis results revealed a significant correlation between low expression levels of KIT, FGF2, NTRK2, CAV1, LEP and poorer prognosis in breast cancer patients. The FISH experiment results indicated that hsa_circ_0059665 exhibits significant downregulation in breast cancer, and its decreased expression is linked to poor prognosis in breast cancer patients. Functional in vitro experiments revealed that overexpression of hsa_circ_0059665 can inhibit proliferation, migration and invasion abilities of breast cancer cells. Further molecular mechanism studies showed that hsa_circ_0059665 exerts its anticancer gene role by acting as a molecular sponge for miR-602. In our study, we constructed and analyzed a circRNA-related ceRNA regulatory network and found that hsa_circ_0059665 can act as a sponge for miR-602 and inhibit the proliferation, invasion and migration of breast cancer cells.

Intestinal obstruction represents a severe intestinal disease associated with higher mortality rates. However, the determinants of mortality in patients with intestinal obstruction remain inadequately understood. This study sought to elucidate the potential risk factors associated with mortality in the context of intestinal obstruction during the COVID-19 pandemic. A retrospective analysis was performed on a cohort of 227 patients diagnosed with intestinal obstruction at the First Hospital of Hebei Medical University, spanning the period from September 7, 2022, to January 7, 2023. The primary endpoint of the study was mortality within four weeks following discharge. Univariate and multivariable logistic regression models were utilized to evaluate the risk factors associated with mortality outcomes. A cohort of 227 patients diagnosed with intestinal obstruction (median age, 59.02 years [IQR, 48.95–70.85 years]) was included in our study. Malignant bowel obstruction (MBO) and COVID-19 were identified as independent risk factors for mortality among these patients. Notably, the mortality rate increased significantly to 38.46

Background:The advancement of early detection and treatment has brought about a significant concern for male breast cancer (MBC) survivors-the emergence of a second primary malignancy (SPM) poses a grave threat to their lives. Among them, second primary prostate cancer (spPCa) holds particular significance. This study aimed to investigate the impact of spPCa on the prognosis of MBC patients. Methods:We performed a retrospective analysis using information from the Surveillance, Epidemiology, and End Results (SEER) database to investigate individuals diagnosed with MBC who also experienced an SPM between 2000 and 2020. Propensity score matching (PSM) was employed to balance the baseline characteristics of individuals with spPCa and those with second primary non-prostate cancer (non-PCa). The impact of spPCa on participant survival was assessed using the Kaplan-Meier method. Furthermore, two nomograms were developed, based on univariate and multifactor Cox regression analyses, to predict overall survival (OS) and cancer-specific survival (CSS). The capacity of the nomograms was evaluated using the concordance index (C-index), calibration curve, receiver operating characteristic (ROC) analysis, and decision curve analysis (DCA). Additionally, a risk stratification system was devised, taking into account the cumulative score of each patient in the nomogram. Results:This study enrolled a total of 885 MBC patients who experienced an SPM, of which 265 (29.9%) were diagnosed with spPCa. Through PSM, 257 pairs of eligible participants were selected. Survival analysis revealed that patients with prostate cancer (PCa) as an SPM have longer OS and CSS compared to those with other types of cancer as an SPM. The participants were randomly divided into a training set and a validation set in a ratio of 7:3. The Cox proportional hazards model was utilized to assess the risk factors associated with survival outcomes. Two nomograms were developed to forecast the 3-, 5-, 8-, and 10-year OS and CSS of male patients who had breast cancer and SPM. The two nomograms exhibited excellent performance in terms of the C-index, ROC curves, calibration plots, and DCA curves, demonstrating their exceptional clinical discriminative ability and predictive utility. In the risk stratification system predicated on the total score of the nomogram, patients deemed high-risk exhibited diminished OS and CSS. Additionally, we created user-friendly web applications to enhance the accessibility of the nomogram in clinical practices, which can be accessed at https://mbcpre.shinyapps.io/DynNomapp_OS/ for OS and https://mbcpre.shinyapps.io/DynNomapp_CSS/ for CSS. Conclusions:MBC patients with spPCa exhibit a more favorable prognosis than those with other SPMs. The two nomograms we constructed could accurately forecast the OS and CSS for MBC patients with spPCa. Patients whose nomograms are stratified as high-risk should gain additional attention. Our nomograms may aid clinicians in personalizing treatment strategies and supporting clinical decisions.

Background The dual role of carcinogenic or tumor suppressor makes Runt related transcription factor 1 (RUNX1) a new diagnostic markers or therapeutic target for colorectal cancer (CRC). In CRC, the relationship between RUNX1 and prognosis, biological function, and potential microRNA directly involved in the regulation of RUNX1 are unclear. Methods Gene expression of RUNX1 in colorectal cancer (CRC) was comprehensively analyzed using data from The Cancer Genome Atlas (TCGA) and Oncomine databases. Kaplan-Meier survival curves were constructed to assess the clinical and prognostic status associated with RUNX1 expression in CRC patients. The correlation between clinical features and RUNX1 expression was analyzed in the GSE17536 dataset using the Chi-square test. The relationship between RUNX1 expression and overall survival (OS) in CRC was investigated through both univariate and multivariate Cox regression analyses. Genes co-expressed with RUNX1 were identified using Spearman correlation analysis. The potential functions of RUNX1 in CRC were elucidated through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. MiRNAs that negatively regulate RUNX1 expression were identified using TargetScan, ENCORI, and miRDB databases. The relationship between miR-200a-3p expression levels and clinicopathologic characteristics, as well as the prognosis of CRC patients, was analyzed using the Chi-square test. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was employed to determine the expression levels of RUNX1 and miR-200a-3p in CRC cell lines (HCT-116, HT-29, SW480, and SW620). The interaction between RUNX1 and miR-200a-3p was confirmed through a luciferase reporter assay. Results Compared with normal tissues, RUNX1 mRNA expression was up-regulated in most cancer tissues, including CRC. RUNX1 expression was closely correlated with TNM stage in CRC patients (P < 0.05). The high expression level of RUNX1 mRNA (HR: 2.198, 95%CI: [1.200, 4.027]) could be used as an independent risk factor for overall survival (OS) in CRC patients. The mRNA level of RUNX1 in CRC patients was significantly correlated with OS (P < 0.01), disease-free survival (DFS) (P < 0.01), and disease-specific survival (DSS) (P < 0.001). RUNX1 co-expressed genes are mainly involved in GO entries such as development and growth, differentiated cell morphogenesis, and KEGG signaling pathways such as adhesion plaques and adhesion junctions. miR-200a-3p may be the miRNAs with direct regulatory role of RUNX1. The expression of miR-200a-3p was significantly correlated with T stage (P = 0.03) and M stage (P = 0.026). Low expression of miR-200a-3p was significantly associated with poor prognosis in CRC patients (P = 0.02). The expression levels of RUNX1 and miR-200a-3p in CRC cell lines were negatively correlated. RUNX1 has specific binding sites with miR-200a-3p. The results of dual luciferase reporter gene detection showed that compared with three groups, Luc-3'UTR + mimic-NC, Luc-NC + miR-200a-3p mimic and Luc-NC + mimic-NC, luciferase activity of Luc-3'UTR + miR-200a-3p mimic group was significantly decreased (P < 0.05), suggesting that miR-200a-3p may be a direct negative regulator of RUNX1. Conclusion High expression of RUNX1 might function as an oncogene in CRC. The up-regulated expression of RUNX1 is associated with poor prognosis after CRC, which can be used as a biomarker of prognosis in CRC patients. This study is the first to report that RUNX1 is a direct negative regulatory target of miR-200a-3p in CRC and can be used as a potential therapeutic target for CRC patients.

Currently, the emergence of the endemic Coronavirus disease (COVID-19) situation still poses a serious threat to public health. However, it remains elusive about the role of fecal microbiota transplantation in treating COVID-19. We performed a randomized, double-blind, placebo-controlled clinical trial enrolling a cohort of 40 COVID-19 patients with mild-moderate symptoms. Our results showed that fecal microbiota transplantation provided an amelioration in diarrhoea (p = 0.026) of digestive system and depression (p = 0.006) of neuropsychiatric-related symptom in COVID-19 patients, respectively. Meanwhile, we found that the number of patients with diarrhoea decreased from 19 to 0 on day 7 after fecal microbiota transplantation treatment, and it was statistically changed compared to the placebo group (p = 0.047). Of note, the serum concentration of aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT, fecal microbiota transplantation, pre vs. post: 0.966 vs. 0.817), a biomarker for predicting long COVID-19, was significantly reduced by fecal microbiota transplantation. In all, our study supports that fecal microbiota transplantation could be a novel therapeutic strategy for COVID-19 patients with diarrhoea and depressive symptoms, which is potentially valuable in ameliorating long COVID-19 symptoms.

Colorectal cancer (CRC), one of the most common malignancies in the world, urgently requires more treatment strategies. Although there has been much research on probiotics, limited research has been done in treating cancer. The purpose of this study was to investigate the role of Bifidobacterium longum (B. longum) in the prevention and treatment of CRC. Through Cell Counting Kit-8 and Colony Formation Assays, 8 h and a B. longum count of 1 × 108 CFU/ml were chosen as the best cocultivation conditions with CRC cells. The role of B. longum in inhibiting the progression of CRC cells was verified by a series of functional and immunofluorescence assays. For instance, in vivo assays have verified that B. longum could alleviate CRC progression. In addition, according to the results of in vivo assays and clinical statistical analysis, B. longum could reduce diarrhea symptoms. Mechanistically, by 16S and RNA sequencing, it was found that B. longum could affect the development of CRC by regulating the composition of gut microbes and enhancing immune function. The B. longum might inhibit the occurrence and development of CRC and relieve diarrhea symptoms by regulating intestinal microbes and immune function.

Background: The function and mechanism of Chromosome 8 open reading frame 76 (C8orf76) in colorectal cancer (CRC) is unknown. In this study, we identified frequent amplification of C8orf76 in CRC, and explored the role of C8orf76 in promoting CRC tumorigenesis and modulating the tumor immune microenvironment (TIME), and its therapeutic implications.Methods: Clinical implication of C8orf76 was determined in three independent human CRC cohorts (n=628). Conditional, intestine-specific C8orf76 knockin (KI) mice were given azoxymethane (AOM)-dextran sulfate-sodium (DSS) to induce CRC. Multi-color flow cytometry was performed to evaluate the TIME. Downstream signaling pathways of C8orf76 were investigated by RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq). Vesicle-like nanoparticles (VNPs)-encapsulated C8orf76-siRNA was constructed to target C8orf76 in vivo.Results: C8orf76 is upregulated in primary CRC compared to adjacent normal tissues in three different CRC cohorts (both P<0.001). Intestine-specific C8orf76 KI significantly increased tumor number and load in the colon tissues of mice treated with AOM-DSS. C8orf76 KI recruited myeloid-derived suppressor cells (MDSCs) but reduced the infiltration and activity of CD8+T cells in colon. Mechanistically, C8orf76 induced transcription of NDST1 (N-Deacetylase And N-Sulfotransferase 1) to activate PI3K-Akt-NF-κB signaling, leading to increased CXCL1 (C-X-C motif chemokine ligand 1) expression that mediates the recruitment of MDSCs. Finally, targeting C8orf76 by knockout or VNPs-encapsulated C8orf76-siRNA potentiated the effect of anti-PD1 in suppressing CRC.Conclusions: C8orf76 mediates an NDST1-PI3K-Akt-NF-κB-CXCL1 axis to promote colorectal tumorigenesis and an immunosuppressive TIME. Targeting of C8orf76 is a potential strategy to boost immunotherapy in CRC.Funding: This project was supported by National Natural Science Foundation of China (NSFC; 82203623; 82103506), Science and Technology Program Grant Shenzhen (JCYJ20190814170401660).Declaration of Interest: No potential conflicts of interest were disclosed.Ethical Approval: Informed consent was obtained for all patients and this study was approved by Clinical Research Ethics Committee of the Peking University Cancer Hospital. All animal studies were performed in accordance with the guidelines approved by the Animal Experimentation Ethics Committee of the Chinese University of Hong Kong.

Colorectal cancer (CRC) is the third most common cancer in the world, with increasing morbidity and mortality. The current diagnosis and treatment plan rely on early detection and comprehensive treatment based on surgery. Still, most patients are in the middle and advanced stage at the time of diagnosis, and the therapeutic effect is very limited. Immunotherapy is a new cancer treatment method. The most commonly used are immune checkpoint inhibitors, specifically anti PD-1/PD-L1 interaction. However, immunotherapy has limitations, with its therapeutic effect closely related to the immune response in the tumor microenvironment. In recent years, the effect of arginine metabolism disorder on the occurrence and development of cancer and tumor immune regulation has attracted wide attention. Studies have confirmed that cancer cells cannot survive without arginine and arginine metabolites. In addition, arginine is essential for the proliferation, differentiation, and survival of tumor-infiltrating lymphocytes. High arginine levels can promote the anti-tumor immune response, thus increasing the effect of tumor immunotherapy. In this paper, the molecular mechanisms of arginine metabolism in the development and immune regulation of CRC are reviewed, with the authors hoping to provide potential evidence for the development of immunotherapy for CRC. Abbreviation CRC = Colorectal cancer, dMMR = Mismatch repair deficient, MSI-H = Microsatellite highly Instability, MSS = Microsatellite stability, TME = Tumor microenvironment, MHC = Major histocompatibility complex, pMMR = Mismatch repair proficient, NOS = Nitric Oxide synthase, NO = Nitric oxide, ASS-1 = Arginine succinate synthetase 1, ASL = Argininosuccinate lyase, ARG = arginase, CAT = Cationic amino acid transporter, AGAT = Arginine-glycine amidinotransferase, ADC = Arginine decarboxylase, ADI = Arginine deiminase, ODC = Ornithine decarboxylase, GCN2 = General control non-depressible 2, mTOR = Mammalian target of rapamycin, HIF-1 = Hypoxia-inducible factor 1, VEGF = Vascular endothelial growth factor, ICI = Immune checkpoint inhibitor, ORR = Objective response rate, DCR = Disease control rate, OS = Overall survival, PFS = Progress free survival, TIL = Tumor-infiltrating lymphocyte, TCM = Central memory T cell

Aims: We investigated the incidence and clinical features of venous thromboembolism (VTE) in inpatients with mental illnesses. Methods: We retrospectively analyzed records of inpatients with mental illnesses and confirmed VTE at The First Hospital of Hebei Medical University between August 2018 and July 2022. We recorded demographic characteristics, psychosis-related conditions, and thrombus distribution. Results: Among 12939 patients diagnosed with mental illness, 156 (1.21%) presented with VTE at the first visit or during the disease course. Crude VTE incidence varied significantly across mental illnesses, being highest in patients with organic mental disorders (5.20%), followed by emotional disorders (1.10%), and others (P < 0.001). Distal and proximal deep venous thromboses (DVT) occurred in 79.17% and 20.84% of patients, respectively. The Hamilton Depression Scale (HAMD) score was higher in patients with proximal DVT than in those with distal DVT (P < 0.001). On multivariate analysis, the HAMD score (odds ratio [OR] 1.173, confidence interval [CI] 1.100-1.251, P < 0.001) was a risk factor and the Hamilton Anxiety Scale (HAMA) (OR 0.862, CI 0.796-0.934, P < 0.001), a protective factor against DVT progression. Conclusion: VTE is not rare in patients with mental illnesses and is most commonly associated with organic mental disorders. Psychosis-related DVT typically shows a significantly high incidence of distal DVT. Prevention and early treatment in patients with severe depression and distal DVT can prevent DVT aggravation.