BackgroundThe presence of lymph node metastasis (LNM) serves as a critical determinant of prognosis in colorectal cancer (CRC), often correlating with markedly unfavorable clinical outcomes. Consequently, this investigation sought to construct and rigorously validate a machine learning (ML) algorithm capable of estimating LNM probability within the CRC population.MethodsThrough the application of logistic regression analysis, six independent predictors were identified: extramural vascular invasion (EMVI), T stage, fibrinogen (FIB), systolic blood pressure (SBP), thrombin time (TT), and alpha-fucosidase (AFU). Subsequently, diverse ML architectures were generated and assessed utilizing receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA).ResultsAmong the evaluated algorithms, the stochastic gradient boosting (gbm) model exhibited superior discriminatory power, yielding area under the curve (AUC) metrics of 0.815 in the training cohort and 0.733 in the external validation set. Calibration assessments revealed a robust concordance between projected probabilities and actual observed events. Notably, the xgbTree algorithm also demonstrated commendable predictive efficacy.ConclusionWe successfully established and verified an ML-based framework designed to forecast LNM risk in individuals with CRC. These computational tools offer clinicians a refined mechanism for the precise identification of nodal involvement, thereby laying the groundwork for formulating personalized therapeutic regimens.

Radiotherapy effectively treats colorectal cancer (CRC), but local recurrence remains common and abscopal effects-regression of tumors distant from irradiated sites-are rarely observed even with immune checkpoint inhibitors. Here we show that the protein kinase NEK8, highly expressed in CRC, promotes radioresistance by suppressing anti-tumor immunity. In radiation-resistant tumors, NEK8 phosphorylates lactate dehydrogenase A (LDHA), driving lactate overproduction. This metabolite promotes histone modifications that silence antigen presentation machinery, while extracellular lactate directly impairs CD8(+) T cell function, collectively excluding CD8(+) T cell from the tumor microenvironment. Pharmacological inhibition of NEK8 using CX6258 restores CD8(+) T cell infiltration and enhances both local and systemic tumor control following radiotherapy. These findings establish NEK8 as a promising therapeutic target for overcoming radioresistance and inducing abscopal responses in CRC.

BackgroundRadiation dose to cardiac conduction nodes may contribute to arrhythmia risks in breast cancer (BC) patients after radiotherapy, yet dosimetric evidence remains limited. This study aimed to evaluate doses to the sinoatrial (SAN) and atrioventricular nodes (AVN) in BC patients treated with intensity-modulated radiation therapy (IMRT) and to clinically validate a deep learning-based autosegmentation model for these structures.MethodsA retrospective analysis was conducted on 87 BC patients who underwent IMRT. Doses to the whole heart, four cardiac chambers, the SAN, and the AVN were evaluated and correlated. For autosegmentation, a convolutional neural network (CNN) was trained on 60 patients, validated on seven, and tested on 20. Segmentation accuracy was assessed using the Dice similarity coefficient (DSC), and dosimetric consistency was compared between automated and manual contours.ResultsIn right-sided BC patients, the SAN received the highest mean dose among cardiac substructures (5.43 Gray [Gy]) under a mean heart dose of 3.39 Gy. Both SAN and AVN doses showed strong correlations with right atrial (RA) dose (R2 for SAN: 0.63 in left- and right-sided cases; for AVN: 0.77 and 0.63, respectively). The autosegmentation model achieved DSCs of 0.83 for SAN and 0.75 for AVN, with no statistically significant dosimetric differences between autosegmented and manual contours.ConclusionsThe SAN receives substantial irradiation in right-sided BC patients during IMRT, and RA dose strongly correlates with conduction node doses, suggesting its potential as a clinical surrogate. The CNN-based autosegmentation method enables accurate and efficient delineation of the SAN and AVN, facilitating reliable dosimetric assessment in clinical practice.

Background: Short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) is used for locally advanced rectal cancer (LARC). However, the pathological complete response (pCR) rate still hovers around 30%. Radiotherapy and immune checkpoint inhibitors have been shown to exert synergistic anticancer effects. This phase II randomized clinical trial aimed to evaluate the efficacy and safety of SCRT followed by capecitabine plus oxaliplatin (CAPOX) and tislelizumab versus SCRT followed by CAPOX alone in LARC. Methods: Patients initially diagnosed with clinical tumor stage 1 to 2, with node involvement and no distant metastasis (cT1-2N+M0) or clinical tumor stage 3 to 4, with any node status and no distant metastasis (cT3-4NanyM0) rectal adenocarcinoma were randomly assigned to receive SCRT (25 Gy in 5 fractions [25 Gy/5F]), followed by 4 cycles of CAPOX combined with tislelizumab (SCRT-TNT-ICI) or CAPOX alone (SCRT-TNT). After total mesorectal excision, 2 cycles of postoperative chemotherapy were administered according to the patient’s preference. The primary end point was the pCR rate, and secondary end points included major pathological response (tumor regression grade 0 or 1), 3-year progression-free survival, 3-year overall survival, and adverse events. Results: Between September 2021 and March 2024, 118 patients were randomized, of whom 111 started the allocated treatment, with 53 and 58 in SCRT-TNT-ICI and SCRT-TNT groups, respectively. Of those, 89 patients had surgical resection, including 45 in the SCRT-TNT-ICI group and 44 in the SCRT-TNT group. The pCR rate was 45.3% (95% confidence interval [CI], 31.5% to 59.8%) in the SCRT-TNT-ICI group compared to 27.6% (95% CI, 16.6% to 40.8%) in the SCRT-TNT group (odds ratio = 2.17; 95% CI, 0.99 to 4.79; P = 0.052). The major pathological response rates were 50.9% (95% CI, 36.6% to 65.2%) and 31.0% (95% CI, 19.5% to 44.6%), respectively (odds ratio = 2.31; 95% CI, 1.06 to 5.01; P = 0.033). During the neoadjuvant treatment period, the incidence of grade 3 to 4 adverse events was comparable between the SCRT-TNT-ICI and SCRT-TNT groups, with anemia being the most common in both groups. Conclusion: This phase II study provides preliminary evidence of promising tumor regression with SCRT-TNT combined with tislelizumab in LARC, warranting further validation in phase III trials. Trial registration: This trial was registered at clinicaltrials.gov (Identifier: NCT05086627).

Objective To explore the relationship between CD8 + tumor-infiltrating lymphocytes (TILs) in rectal cancer, mismatch repair (MMR) status, and patient prognosis. Methods A total of 414 paraffin-embedded tissue samples from patients with pathologically confirmed stage Ⅰ–Ⅲ rectal cancer were included in this study. Tissue microarrays (TMAs) with a thickness of 4 µm were prepared, and immunohistochemical staining was performed using a CD8 antibody to detect the expression of CD8-positive cells. MMR status was assessed using immunohistochemical markers (MSH2, MSH6, MLH1, PMS2). Results CD8 + TILs were expressed on T lymphocytes. Density was significantly associated with tumor invasion depth, lymph node metastasis, and MMR status (P < 0.05), but not with age, sex, surgery type, or tumor size (P > 0.05). Patients with high CD8 + TIL density and stable MMR status had longer overall and progression-free survival. Univariate and multivariate Cox analyses indicated low CD8 + TIL density and unstable MMR status as independent risk factors for poor prognosis. Conclusion CD8 + TIL density and MMR status may serve as combined prognostic biomarkers in rectal cancer, with higher density and stable MMR status linked to better outcomes and potential guidance for immunotherapy strategies.

To evaluate the efficacy of a combined intervention of dietary fiber and probiotics on gut microbiota composition, systemic immune response, nutritional status, and long-term prognosis in patients with advanced colorectal cancer (CRC) undergoing conventional therapy. This retrospective cohort study included 80 patients with advanced CRC and diagnosed malnutrition, treated between May and December 2022. Patients were divided into a control group (n = 40), which received standard nutritional support, and an observation group (n = 40), which received standard support supplemented with a daily formulation of dietary fiber and multi-strain probiotics for 12 weeks. Primary endpoints included changes in immune markers (IgA, IgG, CD4+/CD8+ ratio) and gut microbiota composition (alpha and beta diversity, and specific genera abundance via 16S rRNA sequencing). Secondary endpoints were nutritional status (body mass index [BMI], Patient-Generated Subjective Global Assessment [PG-SGA]), quality of life (WHOQOL-100), and 3-year survival outcomes. Baseline characteristics were well-matched between groups (p > 0.05). After 12 weeks, the observation group exhibited significantly higher levels of IgA (0.95 ± 0.24 vs. 0.78 ± 0.15 g/L), IgG (9.34 ± 1.35 vs. 8.05 ± 1.16 g/L), and an improved CD4+/CD8+ ratio (2.18 ± 0.20 vs. 1.56 ± 0.15) compared to the control group (all p < 0.01). The intervention led to superior improvements in BMI (+ 2.83 kg/m2 vs. + 0.77 kg/m2), PG-SGA scores (4.67 ± 0.44 vs. 6.14 ± 0.50), and WHOQOL-100 scores (98.27 ± 7.38 vs. 72.35 ± 6.79) (all p < 0.001). Microbiota analysis revealed a significant increase in the Shannon diversity index and distinct clustering in beta diversity, alongside enriched relative abundance of Lactobacillus and Bifidobacterium in the observation group (p < 0.001). Importantly, the observation group demonstrated a higher 3-year survival rate (83.5

The gut microbiota is increasingly recognized as a key modulator of cancer pathogenesis and treatment response. We aimed to investigate the efficacy of a targeted dietary intervention on clinical outcomes, gut microbiota, lipid metabolism, and systemic immunity in patients with hepatocellular carcinoma (HCC). In this single-center, prospective, randomized controlled trial, 100 patients with primary HCC were enrolled and randomly assigned (1:1) to an experimental group (n = 50), receiving a structured dietary intervention including probiotics, prebiotics, and specific dietary advice, or a control group (n = 50), receiving routine dietary care. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included changes in gut microbiota composition (16S rRNA sequencing), serum lipid profiles, immune cell subsets (flow cytometry), and quality of life (WHOQOL-100). After a median follow-up of 12 months, the experimental group showed significantly longer median PFS (9.4 vs. 7.3 months; Hazard Ratio [HR] = 0.52, 95

To explore the associations of CD8⁺ tumor-infiltrating lymphocytes (TILs) and mismatch repair (MMR) status with prognosis in patients with rectal cancer. Methods: Formalin-fixed paraffin-embedded (FFPE) tissue specimens were collected from 414 patients with pathologically confirmed stage I–III rectal cancer. Tissue microarrays (TMAs) with a thickness of 4 μm were constructed. Immunohistochemistry (IHC) using anti-CD8 antibody was performed to detect CD8-positive cell expression. MMR status was evaluated via IHC markers including MSH2, MSH6, MLH1 and PMS2. CD8⁺ TILs were expressed in T lymphocytes. CD8⁺ TIL density was significantly correlated with tumor invasion depth, lymph node metastasis and MMR status (P<0.05), whereas no correlations were observed with age, sex, surgical approach or tumor size (P>0.05). Patients with high CD8⁺ TIL density and proficient MMR (pMMR) exhibited longer overall survival (OS) and progression-free survival (PFS). Univariate and multivariate Cox regression analyses demonstrated that low CD8⁺ TIL density and deficient MMR (dMMR) were independent adverse prognostic risk factors. The combination of CD8⁺ TIL density and MMR status may serve as a combined prognostic biomarker for rectal cancer. Higher CD8⁺ TIL density together with pMMR indicates superior patient prognosis, which can provide evidence for developing immunotherapy strategies.

Gastric cancer remains a major cause of cancer mortality, yet its histological and molecular heterogeneity complicates diagnosis and risk stratification. General-purpose pathology foundation models (PFMs) often plateau on fine-grained endpoints central to gastric cancer care, and few have undergone rigorous prospective validation or clinical reader studies. We present GRACE, a Gastric-specific foundation model for Real-world Assessment and Clinical dEcision support. GRACE was developed from multicenter gastric pathology datasets totaling 48,364 primarily HE-stained whole-slide images from 37,493 patients. When evaluated on 28 clinically relevant tasks, GRACE consistently outperformed representative pancancer PFMs, achieving a macro-AUC of 0.9188, with strong performance for precancerous lesion diagnosis (macro-AUC 0.9322), tumor histopathological assessment (macro-AUC 0.9119), molecular profiling (macro-AUC 0.8682), and prognostic prediction. Beyond benchmarking, GRACE's translational value was substantiated through a rigorous evidence chain. Under safety-gated criteria requiring 100

This study characterized the expression profile of miR-153-3p in deciduous pulpitis in children, validated its role in regulating inflammation, oxidative stress, and apoptosis via PTEN targeting, and evaluated its biomarker and therapeutic potential. In a prospective design, pulp tissue was collected from 180 children with deciduous-tooth pulpitis (mild, moderate, or severe) and 180 caries-free controls. qRT-PCR was used to quantify miR-153-3p and PTEN expression, VAS pain scores were recorded, and ROC analysis was performed. An LPS-induced inflammatory model (5 µg/mL, 24 h) was established in human dental pulp stem cells, which were transfected with miR-153-3p mimic or PTEN overexpression plasmid. Cell viability, apoptosis, inflammatory cytokines, and oxidative stress markers were subsequently assessed, and correlations among miR-153-3p, VAS, and PTEN were evaluated. miR-153-3p was significantly downregulated in inflamed pulp and inversely correlated with disease severity and VAS score (r = − 0.323, P < 0.001), with an ROC AUC of 0.814. LPS suppressed miR-153-3p and elevated PTEN in a concentration- and time-dependent manner. miR-153-3p upregulation restored viability, reduced apoptosis, decreased cytokine release, increased SOD activity, and lowered MDA content. Dual-luciferase assays confirmed PTEN as a direct target, and PTEN overexpression reversed the protective effects of miR-153-3p. These findings indicate that miR-153-3p downregulation is associated with inflammation severity, and that miR-153-3p attenuates LPS-induced cellular responses by inhibiting PTEN. Its utility in assessing tissue inflammation and potential as a therapeutic target warrant further in vitro and in vivo validation.

ObjectiveTo investigate the effects of evidence-based nursing under a quantitative assessment strategy (EB-NQAS) on cancer-related fatigue (CRF), self-management ability, quality of life (QoL), and adverse events in lung cancer patients undergoing chemotherapy.MethodsA single-center, prospective, randomized controlled trial (RCT) was conducted, enrolling 150 lung cancer patients undergoing chemotherapy between January 2024 and January 2025. Participants were randomized into the intervention group (n=75) and control group (n=75) using a random number table. The intervention group received EB-NQAS, which featured personalized care plans based on symptom quantification via the Edmonton Symptom Assessment Scale (ESAS), while the control group received routine nursing care. Outcomes were assessed at baseline and 3 months. CRF was assessed using the Piper Fatigue Scale (PFS), self-management ability via the Adult Health Self-Management Scale (AHSMSRS), and QoL via the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC-QLQ-C30). Adverse events were recorded. Data were analyzed using linear mixed-effects models and chi-square tests.ResultsAnalyses were conducted on all 150 randomized participants per the intention-to-treat principle. After 3 months, the EB-NQAS group showed a significantly greater reduction in the total PFS score compared to the control group (22.88 ± 1.72 vs. 25.36 ± 1.63; group × time interaction, P<0.001). The intervention group also demonstrated significantly greater improvements in total AHSMSRS scores (146.00 ± 9.77 vs. 128.45 ± 12.45) and global health status/QoL scores (77.66 ± 9.74 vs. 68.91 ± 9.51) than the control group (all group × time interactions, P<0.001). The incidence of gastrointestinal reactions in the intervention group (5.33%) was lower than that in the control group (18.67%, P = 0.012). No significant differences were observed in other adverse events (P>0.05).ConclusionEvidence-based nursing under a quantitative assessment strategy effectively reduces CRF, improves self-management ability and QoL, and decreases gastrointestinal reactions in lung cancer patients undergoing chemotherapy, demonstrating strong potential for clinical application.

Objective:To identify potential factors influencing the survival prognosis of locally advanced rectal cancer patients receiving neoadjuvant chemoradiotherapy. Methods:A retrospective study was conducted to collect data from January 2009 to December 2020 on 270 patients with locally advanced rectal cancer who were admitted to the Fourth Hospital of Hebei Medical University. The clinical data of patients before and after neoadjuvant chemoradiotherapy and postoperative treatment were compiled. The endpoints of the study were disease-free survival and overall survival of the patients. The univariate and multivariable regression analysis were used to identify factors that influence the patients' survival prognosis. Results:Univariate analysis showed that factors associated with good prognosis in neoadjuvant chemotherapy patients included age <65 years, CEA value ≤5ng/mL, lymphocyte count >1.5×109/L, normal albumin level, NLR ≤2.64, SII ≤683.16, PNI >49.23, tumor distance from the anal margin >5cm, tumor length ≤5cm, tumor invasion of the bowel wall ratio ≤50%, lower T stage and N stage, good tumor regression response, absence of KRAS gene mutation, and mismatch repair protein deficiency. And multivariate analysis showed that age (HR=0.385, P=0.007), NLR (HR=0.294, P=0.011), cT stage (HR=0.287, P<0.001), and tumor regression grade (HR=0.273, P<0.001) were significant factors influencing DFS in patients receiving neoadjuvant chemoradiotherapy. For OS, age (HR=0.497, P=0.035), cT stage (HR=0.387, P=0.001), and tumor regression grade (HR=0.307, P<0.001) were significant factors influencing OS in patients receiving neoadjuvant chemoradiotherapy. Conclusion:Age, cT stage, NLR, and tumor regression grade are significant factors influencing DFS and OS in patients with locally advanced rectal cancer. Younger age, lower cT stage, lower NLR value, and lower tumor regression grade are associated with better survival prognosis.

Objective To investigate the effect of evidence-based nursing intervention guided by a quantitative evaluation strategy on psychological resilience and illness perception in lung cancer patients undergoing chemotherapy. Methods A total of 142 lung cancer patients receiving chemotherapy from March 2024 to March 2025 were enrolled and randomly divided into a study group (receiving evidence-based nursing intervention under a quantitative evaluation strategy, n = 71) and a control group (receiving routine nursing, n = 71). Psychological resilience, illness perception control, coping styles, and complication rates were compared before and 3 months after intervention. Results Before intervention, no significant differences were observed in the scores for psychological resilience domains (optimism, tenacity, strength, total score), illness perception domains (emotional, cognitive, comprehension, total score), or coping styles between the two groups (P > 0.05). After 3 months, the study group showed significantly higher scores in optimism, tenacity, strength, and total psychological resilience than the control group (P < 0.05). Similarly, post-intervention, the study group demonstrated superior scores in all illness perception domains (P < 0.05) and showed a significant shift toward more active and less passive coping styles (P < 0.05). The study group also exhibited lower incidences of gastrointestinal reactions and pulmonary infections (P < 0.05), while no significant differences were observed in hepatorenal toxicity, bone marrow suppression, or phlebitis (P > 0.05). Conclusion Evidence-based nursing intervention guided by quantitative evaluation effectively enhances psychological resilience and illness perception and promotes adaptive coping styles in lung cancer patients undergoing chemotherapy, warranting clinical application.

Background:Lynch syndrome is the most common hereditary colorectal cancer (CRC) syndrome, accounting for 3-5% of all CRC cases. Situs inversus totalis (SIT) is a rare congenital malformation with an incidence of 1 in 8,000 to 1 in 25,000. The co-occurrence of Lynch syndrome and SIT is extremely uncommon. Immune checkpoint inhibitors (ICIs) have demonstrated significant efficacy in treating microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) CRC. Tumors associated with Lynch syndrome frequently exhibit MSI-H, providing a theoretical basis for ICI use. Case presentation:We report a case of bifocal colon cancer associated with Lynch syndrome and SIT. After seven cycles of sintilimab, the patient developed gastrointestinal perforation due to tumor regression, necessitating emergency surgery. The anatomical variations associated with SIT required the surgical team to adopt an alternative approach. Postoperatively, the patient continued sintilimab treatment for 2 years. In June 2024, he underwent a colostomy reversal and proximal colectomy. Pathological examination revealed a tumor regression grade (TRG) of 0, indicating complete pathological remission (pCR), with no recurrence or metastasis detected upon follow-up. Conclusions:The anatomical variations associated with SIT increase the complexity of surgical procedures. Advanced imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) are essential for assessing fine anatomical details and facilitating surgery. ICIs are an effective treatment option for Lynch syndrome-associated CRC, as demonstrated in this case. Future studies should investigate the optimal timing of immunotherapy, combination treatment strategies, and methods to mitigate immune-related toxicities. Such research will help develop comprehensive and personalized treatment plans for Lynch syndrome-associated CRC.

High expression of Solute Carrier Family 11 Member 1(SLC11A1) leads to a poor prognosis in patients with CRC, while the specific role of SLC11A1 in CRC remains unreported. Therefore, this study mainly addressed the preliminary mechanism and specific role of SLC11A1 in CRC. The results showed that six subsequent genes were successfully screened by the line database, and the abnormal expression of SLC11A1 was the most obvious in colorectal cancer patients. Following phenotypic experiments demonstrated that SLC11A1 promoted proliferation, invasion and migration of colorectal cancer cells. SLC11A1 Is also able to downregulate Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL 4), Cyclooxygenase-2 (COX2), NADPH Oxidase 1 (NOX1) and upregulate the expression levels of Hypoxia-Inducible Factor 1 (FIH1), Glutathione Peroxidase 1 (GPX1) protein, inhibit the expression levels of MDA and Fe2+ in colorectal cancer cells, and resist ferroptosis in colorectal cancer cells. SLC11A1 Overexpression can up-regulate the protein expression level of TGFβ1 (Transforming Growth Factor Beta 1), p-Smad 2 / 3, activate TGFβ1 signaling pathway activity, and promote colorectal cancer cell progression. In conclusion, we successfully demonstrated that SLC11A1 confers resistance to ferroptosis in colorectal cancer cells, providing a potential target for the clinical treatment of colorectal cancer.

Objective:This study aimed to evaluate the diagnostic consistency between the Global Leadership Initiative on Malnutrition (GLIM) criteria and the Patient-Generated Subjective Global Assessment (PG-SGA) for identifying malnutrition in patients with pancreatic malignant tumors. Methods:A total of 108 pancreatic cancer patients from our hospital with a Nutritional Risk Screening (NRS) 2002 score ≥ 3 were enrolled. Demographic and clinical data were collected. Nutritional risk was assessed using NRS 2002, while malnutrition was evaluated by PG-SGA and GLIM criteria. The diagnostic consistency between GLIM and PG-SGA was analyzed using Cohen's kappa (κ) and prevalence-adjusted bias-adjusted kappa (PABAK), including a subgroup analysis of malnutrition severity. Pearson correlation examined the relationship between these tools and conventional nutritional indicators, while T-tests were used to compare functional outcomes (handgrip strength) and clinical outcomes (length of stay) between nutritional groups. Results:The mean NRS 2002 score was 3.37 ± 0.98, with 75.0% (81/108) of patients identified as being at nutritional risk. Significant differences in nutritional risk were observed based on age, Body Mass Index (BMI), tumor stage, and tumor size (p < 0.05). Malnutrition prevalence was 60.2% (65/108) according to GLIM criteria and 63.9% (69/108) according to PG-SGA. The consistency analysis between GLIM and PG-SGA yielded a Cohen's kappa value of 0.71 (p < 0.01), indicating substantial agreement. The PABAK was 0.78, confirming substantial agreement after adjusting for prevalence effects. The agreement for malnutrition severity (GLIM Stage 1/2 vs. PG-SGA Moderate/Severe) was moderate (κ = 0.58). Both GLIM and PG-SGA scores demonstrated significant positive correlations with arm circumference (AC), calf circumference (CC), BMI, serum albumin (Alb), and hemoglobin (Hb) levels (p < 0.05). Furthermore, malnutrition diagnosed by either GLIM or PG-SGA was significantly associated with lower handgrip strength and longer hospital stays (p < 0.01). Conclusion:Patients with pancreatic malignant tumors exhibit a high prevalence of nutritional risk and malnutrition. The GLIM criteria and PG-SGA demonstrate good consistency in diagnosing malnutrition in this patient population. Both tools effectively identify patients with functional deficits and poorer clinical outcomes, supporting the utility of GLIM as a practical assessment tool in clinical settings.

BACKGROUND:Approximately 50% of colorectal cancer (CRC) patients exhibit high levels of Fusobacterium nucleatum (Fn), which is associated with chemotherapy resistance. As Fn itself cannot be directly targeted for therapy in vivo, elucidating the mechanism underlying Fn-induced chemotherapy resistance is crucial, though it remains unclear. METHODS:qPCR was used to analyze the correlation between Fn abundance and clinical parameters in 80 human colon cancer samples. The effect of Fn on the sensitivity of colon cancer cells to oxaliplatin was evaluated by clone formation, EdU proliferation and apoptosis assays. RNA sequencing was performed on Fn-infected colon cancer cells to identify differentially expressed genes. Mechanistic studies explored the interaction between PVT1 and ATAD3A, and the role of TLR4/NF-κB pathway in regulating PVT1 expression. RESULTS:qPCR experiments showed that Fn abundance was associated with later clinical stage and shorter RFS. Clone formation, EdU proliferation assay and apoptosis assay showed that Fn could change the sensitivity of colon cancer cells to oxaliplatin. Further RNA sequencing showed that Fn infection could upregulate the expression of long noncoding RNA plasmacytoma variant translocation 1 (PVT1) in colon cancer cells. The abundance of Fn in colon cancer tissues was positively correlated with the level of PVT1, and the mechanism was that PVT1 binds to AAA domain protein 3 (ATAD3A) and prevents its ubiquitination. Fn upregulates ATAD3A expression through PVT1 and inhibits ER stress-mediated cell death. In addition, in colon cancer cells co-cultured with Fn, PVT1 expression is regulated by the TLR4/NF-κB pathway. CONCLUSIONS:This study delineates a pathway where Fn infection promotes oxaliplatin resistancein colon cancer cells by upregulating PVT1 via the TLR4/NF-κB pathway. PVT1 subsequently stabilizes ATAD3A, suppressing cell death. PVT1 is a potential target to overcome the high abundance of Fusobacterium nucleatum leading to oxaliplatin resistance in colon cancer.

INTRODUCTION:Nutritional status may determine the outcomes of patients with pancreatic cancer. This study aimed to investigate the value of sequential nutrition intervention guided by nutritional risk screening for patients undergoing CyberKnife radiotherapy for pancreatic cancer. METHODS:A total of 100 patients with pancreatic cancer were enrolled and randomly divided into a control group (n = 50) and a nutrition intervention group (n = 50). Nutritional status, immunity, QoL, and postoperative complications were compared between groups at baseline, 1 week, and 1 month post-intervention. RESULTS:Pre-intervention, there were no significant differences in nutritional indicators, including total protein (TP), transferrin (TRF), albumin (ALB), or prealbumin (PA), between the two groups. Post-intervention, the nutrition intervention group exhibited higher TP, TRF, ALB, and PA levels compared to the control group at both one week and one month (P < 0.05). Similarly, no significant differences were observed in IgA, IgM, IgG, CD3+, CD4+, CD8+, or CD4+/CD8+ ratios pre-intervention. Post-intervention, the nutrition intervention group showed elevated IgA, IgM, IgG, CD3+, CD4+, and CD8+ levels compared to the control group (P < 0.05), while no significant intergroup difference was found in the CD4+/CD8+ ratio. Quality of life (QoL) scores were comparable pre-intervention but significantly improved in the nutrition intervention group post-intervention at both time points (P < 0.05). The nutrition intervention group also demonstrated a lower incidence of overall complications (P < 0.05). CONCLUSION:Sequential nutrition intervention guided by nutritional risk screening effectively improves nutritional status, immune function, and QoL while reducing complications in pancreatic cancer patients undergoing CyberKnife radiotherapy, warranting clinical application.

Angiogenesis is associated with tumor progression, prognosis, and treatment effect. However, the angiogenesis' underlying mechanisms in the tumor microenvironment (TME) still remain unclear. Understanding the dynamic interactions between angiogenesis and TME in colon adenocarcinoma (COAD) is necessary. We downloaded the transcriptome data and corresponding clinical data of colon cancer patients from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, respectively. We identified two distinct angiogenesis-related molecular subtypes (subtype A and subtype B) and assessed the clinical features, prognosis, and infiltrating immune cells of patients in the two subtypes. According to the prognostic differential genes, we defined two different gene clusters to further explore the correlation between angiogenesis and tumor heterogeneity. Then, we construct the prognostic risk scoring model angiogenesis-related gene (ARG-score) including seven genes (ARMCX2, latent transforming growth factor β binding protein 1, ADAM8, FABP4, CCL11, CXCL11, ITLN1) using Lasso-multivariate cox method. We analyzed the correlation between ARG-score and prognosis, clinicopathological features, TME, molecular feature, cancer stem cells (CSCs), and microsatellite instability (MSI) status. To assess the application value of ARG-score in clinical treatment, immunophenotype score was used to predict patients' immunotherapy response in colon cancer. We found the mutations of ARGs in TCGA-COAD dataset from genetic levels and discussed their expression patterns based on TCGA and GEO datasets. We observed important differences in clinicopathological features, prognosis, immune feature, molecular feature between the two molecular subgroups. Then, we established an ARG-score for predicting OS and validated its predictive capability. A high ARG-score characterized by higher transcription level of ARGs, suggested lower MSI-high (MSI-H), lower immune score, and worse clinical stage and survival outcome. Additionally, the ARG-score was remarkably related to the CSCs index and immunotherapy sensitivity. We found two new molecular subtypes and two gene clusters based on ARGs and established an ARG-score. Multilayered analysis revealed that ARGs were remarkably correlated to the heterogeneity of colon cancer patients and explained the process of tumorigenesis and progression better. The ARG-score can help us better assess patients' survival outcomes and provide guidance for individualized treatment.