Gastrointestinal cancer (GIC) is a common malignant tumour of the digestive system that seriously threatens human health. Due to the unique organ structure of the gastrointestinal tract, endoscopic and MRI diagnoses of GIC in the clinic share the problem of low sensitivity. The ineffectiveness of drugs and high recurrence rates in surgical and drug therapies are the main factors that impact the curative effect in GIC patients. Therefore, there is an urgent need to improve diagnostic accuracies and treatment efficiencies. Nanotechnology is widely used in the diagnosis and treatment of GIC by virtue of its unique size advantages and extensive modifiability. In the diagnosis and treatment of clinical GIC, surface-enhanced Raman scattering (SERS) nanoparticles, electrochemical nanobiosensors and magnetic nanoparticles, intraoperative imaging nanoparticles, drug delivery systems and other multifunctional nanoparticles have successfully improved the diagnosis and treatment of GIC. It is important to further improve the coordinated development of nanotechnology and GIC diagnosis and treatment. Herein, starting from the clinical diagnosis and treatment of GIC, this review summarizes which nanotechnologies have been applied in clinical diagnosis and treatment of GIC in recent years, and which cannot be applied in clinical practice. We also point out which challenges must be overcome by nanotechnology in the development of the clinical diagnosis and treatment of GIC and discuss how to quickly and safely combine the latest nanotechnology developed in the laboratory with clinical applications. Finally, we hope that this review can provide valuable reference information for researchers who are conducting cross-research on GIC and nanotechnology.Graphical Abstract

For many years, the question of whether hyperglycaemia, a manifestation of prediabetes, diabetes mellitus and metabolic syndrome, is a risk factor for colorectal cancer has been intensely studied. In fact, even after the conclusion of several prospective studies, the topic is still controversial. We conducted a systematic review and meta-analysis to investigate the dose-response relationship between blood glucose concentration and the incidence of colorectal cancer. A linear (P = 0.303 for non-linearity) dose-response relationship was observed between fasting plasma glucose (FPG) and colorectal cancer risk without significant heterogeneity. The relative risk (RR) for colorectal cancer per 20 mg/dL increase in FPG was 1.015 (95% CI: 1.012–1.019,P = 0.000). In subgroup analyses, the pooled RRs for colon cancer (CC) and rectal cancer (RC) studies were 1.035 (95% CI 1.008–1.062,P = 0.011) and 1.031 (95% CI: 0.189–5.628,P = 0.972), respectively; in the analysis comparing men and women, the pooled RRs were 1.016 (95% CI: 1.012–1.020,P = 0.000) and 1.011 (95% CI: 0.995–1.027,P = 0.164), respectively. Sensitivity analyses using two methods showed similar results. In conclusion, there is a significant linear dose-response relationship between FPG and the incidence risk of colorectal cancer. For people with diabetes or prediabetes, controlling blood glucose might be useful to prevent colorectal cancer.

Tumor-infiltrating immune cells and prognosis in gastric cancer: a systematic review and meta-analysis Tumor-infiltrating immune cells and prognosis in gastric cancer: a systematic review and meta-analysis

Background: The tumor microenvironment (TME) is an important factor that regulates the progression of colorectal cancer (CRC). Cancer-associated fibroblasts (CAFs) are the main mesenchymal cells in the TME and play a vital role in tumor progression; however, the specific underlying mechanisms require further study. Methods: Multiple single-cell and transcriptome data were analyzed and validated. Primary CAFs isolation, CCK8 assay, co-culture assay, western blotting, multiple immunofluorescence, qRT-PCR, ELISA, immunoprecipitation, ChIP, double luciferase, and animal experiments were used to explore the potential mechanism of MYL9 regulation in CRC. Results: Our findings revealed that MYL9 was predominantly localized and expressed in CAFs rather than in CRC cells, and bioinformatics analysis revealed that high MYL9 expression was strongly associated with poor overall and disease-free survival in various tumors. In addition, high MYL9 expression is closely associated with M2 macrophage infiltration, which can lead to an immunosuppressive microenvironment in CRC, making it insensitive to immunotherapy. Mechanically, MYL9 can regulate the secretion of CAFs on CCL2 and TGF-β1, thus affecting the immune microenvironment and progression of CRC. In addition, MYL9 bounded with IQGAP1 to regulate CCL2 and TGF-β1 secretion through the ERK 1/2 pathway, and CCL2 and TGF-β1 synergistically promoted CRC cells progression through the PI3K-AKT pathway. Furthermore, MYL9 promotes epithelial-mesenchymal transition (EMT) in CRC. During the upstream regulation of MYL9 in CAFs, we found that the EMT transcription factor ZEB1 could bind to the MYL9 promoter in CAFs, enhancing the activity and function of MYL9. Therefore, MYL9 is predominantly expressed in CAFs and can indirectly influence tumor biology and EMT by affecting CAFs protein expression in CRC. Conclusions: MYL9 regulates the secretion of cytokines and chemokines in CAFs, which can affect the immune microenvironment of CRC and promote CRC progression. The relationship between MYL9 expression and CRC clinical staging and immunotherapy is closer in CAFs than in tumor cells; therefore, studies using CAFs as a model deserve more attention when exploring tumor molecular targets in clinical research.

The relationship between systemic inflammation and tumor-associated bacteria is largely unknown in colorectal cancer (CRC). The primary aim of this study was to investigate the prognostic effects of the systemic inflammation response index (SIRI) on the survival outcomes of CRC patients who experienced surgical therapy, and the second aim was to reveal the potential association between SIRI levels and tumor-associated bacteria in CRC. We recruited a cohort of 298 CRC patients who experienced surgical resection in Wuhan Union Hospital. These patients were assigned to the low and high groups based on the cut-off value of SIRI. We utilized 1:1 propensity score matching (PSM) to reduce the potential confounding factors between the low SIRI group (N = 83) and the high SIRI group (N = 83). The total DNA of 166 paraffin-embedded tumor tissues and 24 frozen tumor tissues was extracted and amplified, and 16 S rRNA sequencing was employed to uncover the composition of microbiota between low and high SIRI groups. Survival analysis uncovered that the high SIRI cohort exhibited significantly shorter overall and disease-free survival time than low SIRI companions after PSM. The ROC analyses showed that the prediction abilities of SIRI were much higher than other serum inflammatory biomarkers for survival outcomes. The microbial richness and diversity in the low SIRI group were remarkably higher than those in the high SIRI group. At the phylum level, we found that Proteobacteria, Synergistetes, WPS-2, Thermil, Fusobacteria were enriched in the high SIRI group. Cupriavidus, Thermus, Ochrobactrum, Cupriavidus, Acidovorax were enriched in the high SIRI group at the genus level. 16 S rRNA based on frozen samples also obtained similar results. SIRI is a promising and novel prognostic biomarker among CRC sufferers who underwent surgical removal. There existed significant differences in the diversity and compositions of tumor-associated bacteria between the low and high SIRI groups.