Background Dietary factors have been recognised as contributors to the etiology of colorectal cancer (CRC). Folate is a micronutrient of critical importance to human health, frequently utilized as a dietary supplement. Previous clinical evidence suggested that folate intake is associated with an increased risk of CRC. However, the underlying mechanisms remain unclear. Here, we report that folate supplementation significantly promotes CRC growth and is associated with functional exhaustion of cytotoxic CD8(+) T cell to enhance immune evasion. Methods Using subcutaneous and orthotopic colorectal cancer mouse models, we investigated the impact of folate on CRC progression. Flow cytometry, immunohistochemistry, immunofluorescence, Transwell assays, RNA sequencing, and ChIP-qPCR were employed to elucidate the role and underlying mechanisms of folate in modulating CD8(+) T cell function and recruitment within the tumor. By integrating dietary folate restriction with PD-1 monoclonal antibody therapy in subcutaneous tumor models, we further explored its effects in a preclinical setting. Results Our study indicates that folate directly impairs cytotoxic CD8(+) T cell function and promotes immune escape, thereby accelerating colorectal cancer progression. Mechanistically, folate enhances the expression of SLC19A1, which encodes the folate transporter RFC1, by promoting AKT phosphorylation. Elevated AKT phosphorylation activates the downstream NOTCH1 signaling pathway, leading to a T cell exhaustion phenotype. Meanwhile, folate in the tumor microenvironment suppresses PBX3 expression in CRC cells, thereby reducing CCL5 transcription and impeding CD8(+) T cell recruitment. Furthermore, in vivo dietary folate restriction enhances tumor control and synergizes with anti-PD-1 immunotherapy in CRC. Conclusions This preclinical study suggests that folate may facilitate CRC progression and immune evasion by impairing CD8(+) T cell recruitment and anti-tumor activity. These findings represent a proof-of-concept in mouse immunometabolism offering insights into potential mechanisms underlying folate-driven CRC progression and immune suppression. Broader implications for nutritional interventions or immunotherapy in patients remain speculative at this preclinical stage and would require further clinical investigation.

The Tianhe Procedure is a functional sphincter-preserving surgical approach developed for patients with rectal cancer following radiotherapy. This technique involves proximal extended resection of the colon beyond the pelvic cavity, followed by anastomosis of the non-irradiated proximal colon to the distal rectum or anal canal. This strategy aims to reduce the incidence of anastomotic complications and postoperative bowel dysfunction. However, there is currently a lack of standardized practice guidelines for implementing the Tianhe Procedure in China. Therefore, the Chinese Radiation Intestinal Injury Research Group, the Colorectal Surgery Group of Surgery Branch of the Chinese Medical Association, the Anorectal Branch of Chinese Medical Doctor Association, the Colorectal Cancer Committee of the Chinese Medical Doctor Association, the Colorectal Cancer Committee of China Anti-cancer Association, and the Gastrointestinal Surgical Branch of Guangdong Medical Doctor Association have jointly convened a panel of national experts to discuss and establish this standardized surgical procedure. This standard, based on the latest evidence from literature, research advancements, and expert experience, focuses on key aspects of the Tianhe Procedure, including its precise definition, indications, critical procedural steps, postoperative complications, and functional rehabilitation strategies. It aims to promote standardized implementation and broader clinical adoption of this innovative surgical technique.

OBJECTIVE:The probiotic, Bifidobacterium animalis, (B. animalis) is known to provide health benefits in humans. This study investigated the role of B. animalis in suppressing malignant melanoma progression and modulating tumor immunity. METHODS:Bifidobacterium spp. were isolated from human faeces and verified by whole-genome sequencing. The anti-tumor effects were assessed in B16-F10 melanoma cells. B. animalis efficacy was further evaluated in a syngeneic murine model. Immune profiling was performed with flow cytometry and CD8+ T cell dependency was tested with antibody depletion. Functional metabolites were analyzed by liquid chromatography-mass spectrometry (LC-MS). Transcriptome sequencing elucidated the YAP1 mechanism in CD8+ T cells. Gut microbiota composition was assessed via shotgun metagenomic sequencing. RESULTS:Among the selected Bifidobacterium spp., B. animalis and its conditioned medium effectively inhibited melanoma cell proliferation. Oral administration of B. animalis significantly reduced the growth of B16-F10 allografts, accompanied by an increase in tumor-infiltrating effector T cells. The bioactive component of B. animalis was identified as a < 3-kDa non-protein fraction containing mannose, which phenocopied the anti-tumor and immunostimulatory effects of B. animalis. Microbiota profiling revealed probiotic enrichment in mannose-treated mice. CD8+ T cell depletion abrogated mannose efficacy. Combination therapy with B. animalis and anti-PD-1 synergistically enhanced tumor control and T cell activation. Mechanistically, the bioactive fraction and mannose downregulated YAP1 expression in CD8+ T cells. CONCLUSIONS:B. animalis suppresses melanoma tumorigenesis in mice by restoring gut microbiota and secreting functional mannose. Mannose enhances anti-PD-1 efficacy by inhibiting YAP1 expression in CD8+ T cells, thereby improving effector function. B. animalis may serve as a preventive measure for melanoma management.

Branched-chain amino acid (BCAA) metabolism is dysregulated in colorectal cancer (CRC), with elevated plasma BCAA levels significantly associated with an increased risk of developing the disease. However, whether BCAAs directly promote CRC progression and their underlying mechanisms remain unclear. In this study, we investigated the metabolic alterations in KRAS-mutant CRC. We examined the effects of restricting BCAA supply on the proliferation and metastasis of KRAS-mutant CRC cells both in vitro and in vivo. We found that in KRAS-mutant CRC, BCAAs and their metabolic products accumulate markedly. Restricting the BCAA supply specifically inhibits the proliferation of KRAS-mutant CRC cells but does not affect metastasis. In these cancer cells, enoyl-CoA hydratase-1 (ECHS1), a key enzyme in BCAA metabolism, is downregulated. Furthermore, BCAAs enhance the acetylation of lysine 204 on ECHS1, impairing its ability to bind enoyl-CoA and reducing its catalytic activity. This modification triggers the ubiquitination of ECHS1 and its subsequent degradation, diminishing BCAA catabolism and leading to its cellular accumulation. This accumulation activates the mTORC1 signaling pathway, which induces the transcriptional activation of downstream target proteins and promotes the malignant progression of CRC. Limiting BCAA intake not only suppresses tumor growth in KRAS-mutant CRC but also enhances the efficacy of the KRAS G12D inhibitor MRTX1133 and the monoclonal antibody bevacizumab. Our findings reveal a previously unknown regulatory mechanism of ECHS1 in CRC and offer new potential therapeutic targets.

BACKGROUND:Immune checkpoint blockade (ICB) therapy, while transformative in cancer treatment, is frequently complicated by immune-related colitis (irColitis), driven by poorly understood mechanisms. METHODS:An integrated analysis of single-cell RNA sequencing (scRNA-seq), T cell receptor (TCR) sequencing, and spatial transcriptomics was conducted to identify immune cell populations and associated signaling pathways driving irColitis. In vivo murine models of irColitis, along with flow cytometry and qPCR, were used to further validate these findings. To assess the functional roles of specific signaling pathways and cell types in driving irColitis, in vivo blockade of IL-23 and CXCL9/10 signaling was performed using neutralizing antibodies, and intestinal macrophages were depleted using clodronate liposomes. Additionally, the potential impact of these immune cells and signaling pathways on ICB therapy was evaluated through the integration of scRNA-seq and TCR sequencing with qPCR and flow cytometry. RESULTS:A pathogenic IFNG+IL17+CD4+ T cell subset with dual Th1/Th17 features, high clonal expansion, and differentiation trajectories from tissue-resident memory T cells (TRM) was identified in human irColitis lesions and murine models. IL-23 blockade reduced the frequency of IFNG+IL17+CD4+ T cells and mitigated colitis severity. Mechanistically, IL-23 promoted the expansion and survival of pathogenic Th17 (pTh17) precursors, while CXCL9/10-CXCR3 signaling facilitated their differentiation into IFN-γ-secreting effector cells. Intestinal macrophages were identified as major producers of IL-23, CXCL9, and CXCL10. Macrophage depletion markedly alleviated colitis and reduced pathogenic T cells. Crucially, IFNG+IL17+CD4+ T cells showed no association with antitumor immunity in colorectal cancer immunotherapy responders, suggesting their targeting would not affect ICB efficacy. CONCLUSIONS:IFNG+IL17+CD4+ T cells and CXCL9/10-producing macrophages are key mediators of irColitis. Targeting IL-23 signaling and intestinal macrophages represents a promising strategy to alleviate gut immunopathology without compromising the efficacy of ICB therapy.

BACKGROUND:Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) remains controversial in locally advanced colorectal cancer (CRC). This study aimed to evaluate its survival benefits and safety. METHODS:A retrospective cohort of 3008 CRC patients undergoing resection (2014-2019) was analyzed. Propensity score matching (PSM) generated 188 HIPEC and 188 control patients. Outcomes included operative metrics, complications (Clavien-Dindo ≥III), and 3-year overall survival (OS)/disease-free survival (DFS). Multivariable Cox regression identified prognostic factors. RESULTS:Post-PSM, HIPEC required longer operative time (215 vs 185 minutes) and hospital stay (9.2 vs 7.5 days), with comparable major complications (12.8% vs 10.6%, P > 0.05). HIPEC showed superior 3-year OS (87.2% vs 80.5%, HR = 0.54, P = 0.029) and DFS (81.7% vs 75.2%, HR = 0.59, P = 0.037). Multivariable analysis confirmed HIPEC (OS: HR = 0.54, 95% CI: 0.31-0.94; DFS: HR = 0.59, 95% CI: 0.37-0.93) and laparoscopic approach as independent survival predictors. CONCLUSION:Prophylactic HIPEC (43°C, 60-90 minutes) may improve survival in locally advanced CRC without increasing major complications, supporting its integration into surgical practice. Further validation through multicenter trials is warranted.

Laparoscopic exploration (LE) is crucial for diagnosing intra-abdominal metastasis (IAM) in advanced gastric cancer (GC). However, overlooking single, tiny, and occult IAM lesions during LE can severely affect the treatment and prognosis due to surgeons’ visual misinterpretations. To address this, we developed the artificial intelligence laparoscopic exploration system (AiLES) to recognize IAM lesions with various metastatic extents and locations. The AiLES was developed based on a dataset consisting of 5111 frames from 100 videos, using 4130 frames for model development and 981 frames for evaluation. The AiLES achieved a Dice score of 0.76 and a recognition speed of 11 frames per second, demonstrating robust performance in different metastatic extents (0.74–0.76) and locations (0.63–0.90). Furthermore, AiLES performed comparably to novice surgeons in IAM recognition and excelled in recognizing tiny and occult lesions. Our results demonstrate that the implementation of AiLES could enhance accurate tumor staging and assist individualized treatment decisions.

BACKGROUND:Patients with colorectal cancer (CRC) exhibiting microsatellite instability (MSI)-high generally demonstrate a favorable response to immunotherapy. In contrast, the efficacy of immunotherapy in microsatellite-stable (MSS) CRC patients is considerably restricted. This study sought to evaluate the effectiveness of immunotherapy in MSS patients characterized by homologous recombination deficiency (HRD) as opposed to those with homologous recombination proficiency (HRP). AIM:To investigate and compare the clinicopathological characteristics, treatment modalities, and outcomes between the HRD and HRP groups in CRC. METHODS:Next-generation sequencing was performed on 268 CRC patients to identify tumor-associated genetic alterations and assess their HRD scores and MSI status. Patients with HRD-related gene alterations or an HRD score ≥ 30 were classified into the HRD group, while the remaining patients were assigned to the HRP group. Clinical data, including staging and treatment regimens, were collected for analysis. Cox regression and Kaplan-Meier survival curves were employed to evaluate whether the HRD group demonstrated improved survival outcomes following immunotherapy treatment. RESULTS:Among the 268 patients, 64 were classified into the HRD group, which had a higher proportion of early-stage CRC diagnoses compared to the HRP group. Kaplan-Meier survival curves indicated significantly better survival rates in the HRD group compared to the HRP group across all cohorts, as well as among MSS patients treated with immunotherapy (P < 0.05). CONCLUSION:This study demonstrates that CRC patients with HRD have a more favorable prognosis and suggests that HRD status could serve as a predictive marker for immunotherapy response in MSS patients.

Colorectal cancer (CRC) is a leading global health issue, ranking third in incidence and second in cancer mortality. Immunotherapy, effective mainly in mismatch repair-deficient CRC, may benefit from dietary interventions. This study investigates caffeine's potential to boost programmed death-1 (PD-1) immunotherapy efficacy in CRC, revealing that caffeine significantly reduces tumor growth, extends survival, and enhances CD8+ T cell activity in CRC by suppressing kynurenine pathway. Mechanistically, caffeine decreases kynurenine via the Krüppel-like factor 4 (KLF4)- Collagen type XII alpha 1 (COL12A1)- Mitogen-Activated Protein Kinase (MAPK)-Indoleamine 2,3-dioxygenase 1 (IDO1) axis, mitigating CD8+ T cell exhaustion. Combining caffeine with PD-1 therapy further prolongs survival, highlighting the value of integrating nutritional strategies into cancer treatment to improve outcomes and broaden therapeutic options. Here, we show caffeine can enhance PD-1 immunotherapy in CRC by suppressing kynurenine pathway, suggesting its potential as an adjunctive dietary therapy.

Background Tumourigenesis in right-sided and left-sided colons demonstrated distinct features. Objective We aimed to characterise the differences between the left-sided and right-sided adenomas (ADs) representing the early stage of colonic tumourigenesis. Design Single-cell and spatial transcriptomic datasets were analysed to reveal alterations between right-sided and left-sided colon ADs. Cells, animal experiments and clinical specimens were used to verify the results. Results Single-cell analysis revealed that in right-sided ADs, there was a significant reduction of goblet cells, and these goblet cells were dysfunctional with attenuated mucin biosynthesis and defective antigen presentation. An impairment of the mucus barrier led to biofilm formation in crypts and subsequent bacteria invasion into right-sided ADs. The regions spatially surrounding the crypts with biofilm occupation underwent an inflammatory response by lipopolysaccharide (LPS) and an apoptosis process, as revealed by spatial transcriptomics. A distinct S100A11 + epithelial cell population in the right-sided ADs was identified, and its expression level was induced by bacterial LPS and peptidoglycan. S100A11 expression facilitated tumour growth in syngeneic immunocompetent mice with increased myeloid-derived suppressor cells (MDSC) but reduced cytotoxic CD8+ T cells. Targeting S100A11 with well-tolerated antagonists of its receptor for advanced glycation end product (RAGE) (Azeliragon) significantly impaired tumour growth and MDSC infiltration, thereby boosting the efficacy of anti-programmed cell death protein 1 therapy in colon cancer. Conclusion Our findings unravelled that dysfunctional goblet cells and consequential bacterial translocation activated the S100A11-RAGE axis in right-sided colon ADs, which recruits MDSCs to promote immune evasion. Targeting this axis by Azeliragon improves the efficacy of immunotherapy in colon cancer.

BACKGROUND:Colorectal cancer liver metastasis (CRLM) is characterized by an immunosuppressive microenvironment and a blunted response to immunotherapy. Notably, tumor-associated macrophages (TAMs) play a critical role in modulating immune responses and exhibit significant heterogeneity in CRLM. Sphingosine kinase 1 (SPHK1) serves as a pivotal kinase in maintaining the balance between ceramide and sphingosine-1-phosphate (S1P) levels. However, the effects of SPHK1 within TAMs on tumor immune evasion during CRLM remain elusive. This study aimed at investigating the role of TAM-intrinsic SPHK1 in tumor immunosuppressive microenvironment in CRLM. METHODS:SPHK1 expression levels in TAMs were estimated by immunofluorescence and bioinformatics analysis. Several animal models were established to elucidate the role of SPHK1 in tumor immunity reprogramming in vivo. Flow cytometry, cytokine assay, and transwell assay were conducted to investigate the effects of SPHK1 in TAMs in cell-cell communication in vitro. RNA-sequencing, Western blotting, and quantitative real-time polymerase chain reaction were used to explore the molecular mechanism by which SPHK1 activated NLR family pyrin domain containing 3 (NLRP3) inflammasome in TAMs. RESULTS:We found that SPHK1 was mainly expressed in TAMs and identified SPHK1+ TAMs as associated with CRLM and diminished efficacy of immunotherapy in human patients. These SPHK1+ TAMs exhibited strong immunosuppressive activities by inducing CD8+ T cell exhaustion with high programmed cell death 1 (PD-1) expression via the interaction between TAMs and CRC cells. Mechanistically, SPHK1-produced S1P exerted an autocrine effect to activate NLRP3 inflammasome and interleukin 1 beta (IL-1β) release via nuclear factor-kappa B (NF-κB) and hypoxia inducible factor 1 subunit alpha (HIF-1α) signaling in TAMs. Paracrine IL-1β then upregulated the expression of monocyte chemoattractants and ADAM metallopeptidase domain 17 (ADAM17) sheddase in CRC cells, resulting in TAM infiltration and CD8+ T cell dysfunction in the liver microenvironment. Furthermore, combining SPHK1-targeting treatments with anti-PD-1 therapy or radioimmunotherapy largely stalled liver metastasis and caused a significant extension of lifespan in preclinical mouse models. CONCLUSIONS:Our findings highlighted the role of SPHK1 of TAMs in facilitating CRLM by promoting CD8+ T cell dysfunction and immunosuppressive microenvironment. Combining SPHK1 blockade with anti-PD-1 therapy may be a promising treatment regimen for patients with CRLM.

Background Laparoscopic surgery is increasingly used for rectal cancer, but the long-term oncological outcomes for low rectal cancer have not been fully established. We aimed to evaluate the 3-year survival outcomes of laparoscopic surgery versus open surgery in the treatment of low rectal cancer. Methods This multicentre, randomised, controlled, non-inferiority trial was conducted at 22 tertiary hospitals in China. Individuals aged 18-75 years with histologically confirmed cT1-2N0, cT3-4aN0, or cT1-4aN1-2 rectal adenocarcinoma within 5 cm from the dentate line were eligible for inclusion. Participants were randomly assigned (2:1) to undergo laparoscopic surgery or open surgery. Central randomisation was conducted using a web response system, and was stratified by clinical stage, age, sex, BMI, and American Society of Anesthesiologists classification. Investigators, patients and statisticians were not masked to group allocation. The primary outcome was 3-year disease-free survival, defined as the time from the date of surgery to the date of locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first. Non-inferiority was defined as a lower limit of onesided 975% CI for group difference (laparoscopic surgery group minus open surgery group) of greater than -10%. The primary analyses were performed in the modified intention-to-treat population, which excluded patients with distant metastasis discovered during surgery and those who did not undergo surgery or underwent local resection only. The trial is registered with ClinicalTrials.gov, NCT01899547, and has been completed. Findings Between Nov 12, 2013, and June 6, 2018, 1070 patients were enrolled and randomly assigned to treatment. 1039 patients (685 in the laparoscopic surgery group and 354 in the open surgery group; median age 57 years, IQR 50 to 64; 620 [60%] male and 419 [40%] women) were included in the modified intention-to-treat analysis. 3-year disease-free survival was 814% (95% CI 782 to 841) in the laparoscopic surgery group and 798% (752 to 836) in the open surgery group (hazard ratio [HR] 092, 95% CI 069 to 123; p=056). The difference between groups was 160% (one-sided 975% CI -334 to infinity, p<00001 for non-inferiority). 3-year overall survival was 917% (95% CI 893 to 935) in the laparoscopic surgery group and 937% (906 to 958) in the open surgery group (HR 134, 95% CI 082 to 219; p=024). 3-year locoregional recurrence was 37% (95% CI 25 to 53) and 23% (11 to 43), respectively (HR 164, 95% CI 074 to 363; p=022). 5-year overall survival was 846% (95% CI 815 to 871) and 866% (825 to 898) in the open group (HR 116, 95% CI 082 to 164; p=041). Interpretation Laparoscopic surgery performed by experienced surgeons is non-inferior to open surgery for 3-year disease-free survival among patients with low rectal cancer. These results support the use of laparoscopic surgery for low rectal cancer. Funding The Key Clinical Specialty Discipline Construction Program of the National Health and Family Planning Commission of China; Minimally Invasive Medical Center Construction Program, Fujian Province, China; and Joint Funds for the Innovation of Science and Technology, Fujian Province, China. Copyright (c) 2024 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

BACKGROUND:Disorder of cell cycle represents as a major driver of hepatocarcinogenesis and constitutes an attractive therapeutic target. However, identifying key genes that respond to cell cycle-dependent treatments still facing critical challenges in hepatocellular carcinoma (HCC). Increasing evidence indicates that dynein light chain 1 (DYNLL1) is closely related to cell cycle progression and plays a critical role in tumorigenesis. In this study, we explored the role of DYNLL1 in the regulation of cell cycle progression in HCC. METHODS:We analysed clinical specimens to assess the expression and predictive value of DYNLL1 in HCC. The oncogenic role of DYNLL1 was determined by gain or loss-of-function experiments in vitro, and xenograft tumour, liver orthotopic, and DEN/CCl4-induced mouse models in vivo. Mass spectrometry analysis, RNA sequencing, co-immunoprecipitation assays, and forward and reverse experiments were performed to clarify the mechanism by which DYNLL1 activates the interleukin-2 enhancer-binding factor 2 (ILF2)/CDK4 signalling axis. Finally, the sensitivity of HCC cells to palbociclib and sorafenib was assessed by apoptosis, cell counting kit-8, and colony formation assays in vitro, and xenograft tumour models and liver orthotopic models in vivo. RESULTS:DYNLL1 was significantly higher in HCC tissues than that in normal liver tissues and closely related to the clinicopathological features and prognosis of patients with HCC. Importantly, DYNLL1 was identified as a novel hepatocarcinogenesis gene from both in vitro and in vivo evidence. Mechanistically, DYNLL1 could interact with ILF2 and facilitate the expression of ILF2, then ILF2 could interact with CDK4 mRNA and delay its degradation, which in turn activates downstream G1/S cell cycle target genes CDK4. Furthermore, palbociclib, a selective CDK4/6 inhibitor, represents as a promising therapeutic strategy for DYNLL1-overexpressed HCC, alone or particularly in combination with sorafenib. CONCLUSIONS:Our work uncovers a novel function of DYNLL1 in orchestrating cell cycle to promote HCC development and suggests a potential synergy of CDK4/6 inhibitor and sorafenib for the treatment of HCC patients, especially those with increased DYNLL1.

PURPOSE Complete mesocolic excision (CME) is being increasingly used for the treatment of right-sided colon cancer, although there is still no strong evidence that CME provides better long-term oncological outcomes than D2 dissection. The controversy is mainly regarding the survival benefit from extended lymph node dissection emphasized by CME. METHODS This multicenter, open-label, randomized controlled trial (ClinicalTrials.gov identifier: NCT02619942 ) was performed across 17 hospitals in China. Patients diagnosed with stage T2-T4aNanyM0 or TanyN + M0 right-sided colon cancer were randomly assigned (1:1) to undergo either CME or D2 dissection during laparoscopic right colectomy. The primary outcome was the 3-year disease-free survival (DFS), and the main secondary outcome was the 3-year overall survival (OS). RESULTS Between January 11, 2016, and December 26, 2019, 1,072 patients were randomly assigned (536 patients to CME and 536 patients to D2 dissection). In total, 995 patients (median age 61 years, 59% male) were included in the primary analysis (CME [n = 495] v D2 dissection [n = 500]). No significant differences were found between the groups in 3-year DFS (hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.02]; P = .06; 86.1% in the CME group v 81.9% in the D2 group) or in 3-year OS (HR, 0.70 [95% CI, 0.43 to 1.16]; P = .17; 94.7% in the CME group v 92.6% in the D2 group). CONCLUSION This trial failed to find evidence of superior DFS outcome for CME compared with standard D2 lymph node dissection in primary surgical excision of right-sided colon cancer. Standard D2 dissection should be the routine procedure for these patients. CME should only be considered in patients with obvious mesocolic lymph node involvement.

Inflammatory bowel diseases (IBDs) are chronic, relapsing, and inflammatory disorders of the gastrointestinal tract characterized by abnormal immune responses. Recently, STING has emerged as a promising therapeutic target for various autoinflammatory diseases. However, few STING-selective small molecules have been investigated as novel strategies for IBD. In this study, we sought to examine the effects of PROTAC-based STING degrader SP23 on acute colitis and explore its underlying mechanism. SP23 treatment notably alleviates dextran sulfate sodium (DSS)-induced colitis. Pharmacological degradation of STING significantly reduced the production of inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, and inhibited macrophage polarization towards the M1 type. Furthermore, SP23 administration decreased the loss of tight junction proteins, including ZO-1, occludin, and claudin-1, and downregulated STING and NLRP3 signaling pathways in intestinal inflammation. In vitro, STING activated NLRP3 inflammasome-mediated pyroptosis in intestinal epithelial cells, which could be abrogated by SP23 and STING siRNA intervention. In conclusion, these findings provide new evidence for STING as a novel therapeutic target for IBD, and reveal that hyperactivation of STING could exaggerate colitis by inducing NLRP3/Caspase-1/GSDMD axis mediated intestinal epithelial cells pyroptosis.

With the rapid development of medical imaging technology and computer technology, the medical imaging artificial intelligence of computer-aided diagnosis based on machine learning has become an important part of modern medical diagnosis. With the application of medical image security technology, people realize that the difficulty of its development is the inherent defect of advanced image processing technology. This paper introduces the background of colorectal cancer diagnosis and monitoring, and then carries out academic research on the medical imaging artificial intelligence of colorectal cancer diagnosis and monitoring and machine learning, and finally summarizes it with the advanced computational intelligence system for the application of safe medical imaging.In the experimental part, this paper wants to carry out the staging preparation stage. It was concluded that the staging preparation stage of group Y was higher than that of group X and the difference was statistically significant. Then the overall accuracy rate of multimodal medical image fusion was 69.5% through pathological staging comparison. Finally, the diagnostic rate, the number of patients with effective treatment and satisfaction were analyzed. Finally, the average diagnostic rate of the new diagnosis method was 8.75% higher than that of the traditional diagnosis method. With the development of computer science and technology, the application field was expanding constantly. Computer aided diagnosis technology combining computer and medical images has become a research hotspot.

Several studies have observed that some stage III colorectal cancer (CRC) patients cannot benefit from standard adjuvant chemotherapy. However, there is no unified screening standard to date. Consecutive patients with pathologically confirmed colon adenocarcinoma treated in 3 centers between January 2016 and December 2018 were included. Patients were divided into four groups according to different stages and positive paracolic lymph-node ratio (P-LNR) [Cohort 1: pT1-3N0M0, Cohort 2: pT1-3N + (P-LNR ≤ 0.15)M0, Cohort 3: pT4N0M0, Cohort 4: stage III patients except for pT1-3N + (P-LNR ≤ 0.15)M0], and further overall survival was compared by Kaplan–Meier method. The univariate and multivariate analyses were employed for cox proportional hazards model. We retrospectively reviewed 5581 consecutive CRC patients with, and 2861 eligible patients were enrolled for further analysis. The optimal cut-off value of P-LNR in our study was 0.15. There was no significant difference in OS (91.36 vs. 93.74