Four-year variation in pathogen distribution and antimicrobial susceptibility of urosepsis: a single-center retrospective analysis.

Background: Urosepsis is a common disease in urology, which is characterized by high treatment costs and high mortality. In the treatment of sepsis, anti-infection therapy is the most important means. However, the effect of empirical anti-infection therapy is often not ideal. Therefore, it is necessary to continuously monitor the prevalence of bacterial isolates in the blood culture of patients with urinary sepsis and their sensitivity to antibacterial drugs. This is of great significance to improve the efficacy of empirical antibiotic therapy for urosepsis. Objective: To elucidate the landscape of prevailing bacterial profiles and their antimicrobial susceptibilities in urosepsis cases, and to furnish robust clinical evidence to underpin the timely initiation of empirical antibiotic treatment. Methods: Collect the basic information and blood culture results of patients with urosepsis hospitalized from 2017 to 2020. Retrospective analysis of bacterial species and antimicrobial susceptibility in urosepsis and changes over 4 years. Results: Gram-negative bacteria (178 isolates, 75.11%) constituted the main pathogens causing urosepsis, followed by Gram-positive bacteria (46 isolates, 19.41%) and fungus (13 isolates, 5.48%). The sensitivity of ertapenem, meropenem, amikacin, and imipenem to Gram-negative bacteria all exceeded 85%. The sensitivity rates of levofloxacin, gentamicin, and ciprofloxacin are decreasing every year (p < 0.05). Tigecycline, vancomycin, and linezolid exhibited excellent sensitivity against Gram-positive bacteria. Among fungi, fluconazole demonstrated universal sensitivity, while itraconazole-resistant isolates have been found, and amphotericin B is still effective. Conclusion: Analysis of blood culture results of patients more accurately reflected the etiology of urosepsis, mainly Escherichia coli, Enterococcus, and Klebsiella pneumoniae. If there are no definitive blood culture results, empiric treatment of urosepsis should not include fluoroquinolone antibiotics. Cefepime, cefoxitin, and ceftazidime are the most sensitive antibiotics to Gram-negative bacteria besides carbapenem antibiotics. In addition, the current situation regarding extended-spectrum ß-lactamase-producing bacteria and carbapenem-resistant Enterobacteriaceae bacteria resistance is extremely concerning with limited therapeutic options available. Strengthening antibiotic management practices and exploring novel antibacterial agents can help mitigate this issue.

Synergistic Glutathione Depletion and STING Activation to Potentiate Dendritic Cell Maturation and Cancer Vaccine Efficacy.

Dendritic cell (DC) maturation and antigen presentation are key factors for successful vaccine-based cancer immunotherapy. This study developed manganese-based layered double hydroxide (Mn-LDH) nanoparticles as a self-adjuvanted vaccine carrier that not only promoted DC maturation through synergistically depleting endogenous glutathione (GSH) and activating STING signaling pathway, but also facilitated the delivery of model antigen ovalbumin (OVA) into lymph nodes and subsequent antigen presentation in DCs. Significant therapeutic-prophylactic efficacy of the OVA-loaded Mn-LDH (OVA/Mn-LDH) nanovaccine was determined by the tumor growth inhibition in the mice bearing B16-OVA tumor. Our results showed that the OVA/Mn-LDH nanoparticles could be a potent delivery system for cancer vaccine development without the need of adjuvant. Therefore, the combination of GSH exhaustion and STING pathway activation might be an advisable approach for promoting DC maturation and antigen presentation, finally improving cancer vaccine efficacy.

Life table and cold tolerance of laboratory-reared Penthaleus major (Acari: Penthaleidae).

Penthaleus major (Dugés) is a significant agricultural pest that attacks various pasture, vegetable, and crop plants. Temperature plays a critical role in the life history of P. major. However, there is limited understanding of its life table at different temperatures and cold tolerance. This study aimed to elucidate the performance of P. major by constructing life tables at 6, 9, 12, 15, 18, 21, and 24 °C. The results showed that P. major successfully developed at 9‒21 °C. However, no adults emerged at 6°C, and no eggs hatched at 24 °C. The highest intrinsic rate of increase (r), finite rate of increase (λ), net reproductive rate (R0), and gross reproductive rate (GRR) were observed at 12 °C. The supercooling point (SCP) exhibited significant variations at different developmental stages. The highest SCP (‒9.75 °C) was recorded in 10-day-old female adults, while the lowest SCP (‒24.37 °C) was observed in larvae. For female adult mites of 2, 6, and 10 days old, the low lethal temperatures (LLT50) were ‒14.63, ‒12.03, and ‒11.08 °C, respectively. This study provided valuable insights for modeling and predicting the population dynamics of P. major in the field and offered implications for developing successful management strategies.

Optimisation of the Mechanical Properties and Mix Proportion of Multiscale-Fibre-Reinforced Engineered Cementitious Composites.

Engineered cementitious composites (ECCs) are cement-based composite materials with strain-hardening and multiple-cracking characteristics. ECCs have multiscale defects, including nanoscale hydrated silicate gels, micron-scale capillary pores, and millimetre-scale cracks. By using millimetre-scale polyethylene (PE) fibres, microscale calcium carbonate whiskers (CWs), and nanoscale carbon nanotubes (CNTs) as exo-doped fibres, a multiscale enhancement system was formed, and the effects of multiscale fibres on the mechanical properties of ECCs were tested. The Box-Behnken experimental design method, which is a response surface methodology, was used to construct a quadratic polynomial regression equation to optimise ECC design and provide an optimisation of ECC mix proportions. The results of this study showed that a multiscale reinforcement system consisting of PE fibres, CWs, and CNTs enhanced the mechanical properties of ECCs. CWs had the greatest effect on the compressive strengths of highly ductile-fibre-reinforced cementitious composites, followed by CNTs and PE fibres. PE fibres had the greatest effect on the flexural and tensile strengths of high-ductility fibre-reinforced cementitious composites, followed by CWs and CNTs. The final optimisation results showed that when the ECC matrix was doped with 1.55% PE fibres, 2.17% CWs, and 0.154% CNTs, the compressive strength, flexural strength, and tensile strength of the matrix were optimal.

Hydroxycitric acid prevents hyperoxaluric-induced nephrolithiasis and oxidative stress via activation of the Nrf2/Keap1 signaling pathway.

Nephrolithiasis is a common and frequently-occurring disease in the urinary system with high recurrence. The present study aimed to explore the protective effect and underlying mechanism of hydroxycitric acid (HCA) in hyperoxaluria-induced nephrolithiasis in vitro and in vivo. Crystal deposition and pathophysiological injury in rat models of glyoxylate-induced nephrolithiasis were examined using H&E staining. Cell models of nephrolithiasis were established by oxalate-treated renal tubular epithelial cells. The levels of oxidative stress indexes were determined by ELISA kits. Cell proliferation in vivo and in vitro was evaluated using a cell counting kit-8 (CCK-8) assay and Ki-67 cell proliferation detection kit. Cell apoptosis was measured by flow cytometry and TUNEL staining. The protein levels were examined by western blotting. Our results showed that HCA administration significantly reduced crystal deposition and kidney injury induced by glyoxylate. HCA also alleviated oxidative stress via upregulating the antioxidant enzyme activities of superoxide dismutase (SOD) and catalase (CAT) and reducing the malondialdehyde (MDA) content. Moreover, HCA treatment promoted cell proliferation and inhibited apoptosis of renal tubular epithelial cells exposed to hyperoxaluria. Of note, Nrf2 activator dimethyl fumarate (DMF) exerted the same beneficial effects as HCA in nephrolithiasis. Mechanistically, HCA prevented crystal deposition and oxidative stress induced by hyperoxaluria through targeting the Nrf2/Keap1 antioxidant defense pathway, while knockdown of Nrf2 significantly abrogated these effects. Taken together, HCA exhibited antioxidation and anti-apoptosis activities in nephrolithiasis induced by hyperoxaluria via activating Nrf2/Keap1 pathway, suggesting that it may be an effective therapeutic agent for the prevention and treatment of nephrolithiasis.

Succinate Dehydrogenase Defects Giant Renal Cell Carcinoma.

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a new subtype of RCC included in the 2016 edition of the WHO classification in RCC. SDH-defective RCC accounts for 0.05-0.2%, and preoperative diagnosis is difficult. We report a severe adherent RCC of inferior vena cava that underwent open radical nephrectomy after preoperative renal artery embolization. Postoperative histopathological examination diagnosed SDH-defective RCC; the clinicopathological stage was pT2b. After 10 months of follow-up, the patient had no evidence of disease recurrence. For patients with large RCC, interventional embolization can be selected to reduce intraoperative bleeding and blood transfusion, and it is recommended to complete interventional surgery within 3-4 h before surgery. SDH-deficient RCC is difficult to distinguish from other renal tumors in imaging, so immunohistochemical examination of SDHB is recommended for young and middle-aged patients, especially those under 45.

An engineered hypercompact CRISPR-Cas12f system with boosted gene-editing activity.

Compact CRISPR-Cas systems offer versatile treatment options for genetic disorders, but their application is often limited by modest gene-editing activity. Here we present enAsCas12f, an engineered RNA-guided DNA endonuclease up to 11.3-fold more potent than its parent protein, AsCas12f, and one-third of the size of SpCas9. enAsCas12f shows higher DNA cleavage activity than wild-type AsCas12f in vitro and functions broadly in human cells, delivering up to 69.8% insertions and deletions at user-specified genomic loci. Minimal off-target editing is observed with enAsCas12f, suggesting that boosted on-target activity does not impair genome-wide specificity. We determine the cryo-electron microscopy (cryo-EM) structure of the AsCas12f-sgRNA-DNA complex at a resolution of 2.9 Å, which reveals dimerization-mediated substrate recognition and cleavage. Structure-guided single guide RNA (sgRNA) engineering leads to sgRNA-v2, which is 33% shorter than the full-length sgRNA, but with on par activity. Together, the engineered hypercompact AsCas12f system enables robust and faithful gene editing in mammalian cells.

Optimal Design of Multi-Scale Fibre-Reinforced Cement-Matrix Composites Based on an Orthogonal Experimental Design.

Cement-matrix composite are typical multi-scale composite materials, the failure process has the characteristics of gradual, multi-scale and multi-stage damage. In order to delay the multi-stage damage process of cement-matrix composites, the defects of different scales are suppressed by using different scales of fibres and fly ash (FA), and the overall performance of cement-matrix composites is improved, a new multi-scale fibre-reinforced cement-based composite composed of millimetre-scale polyvinyl alcohol fibre (PVA), micron-scale calcium carbonate whisker (CW), and nano-scale carbon nanotubes (CNTs) was designed in this study. The compressive strength, flexural strength, splitting tensile strength, and chloride ion permeability coefficient were used as assessment indices by the orthogonal test design. The impacts of the three fibre scales and fly ash on each individual index were examined, and the overall performance of the multi-scale fibre-reinforced cementitious materials (MSFRCC) was then optimized using grey correlation analysis. The optimized mix ratio for overall performance was PVA: 1.5%, CW: 2%, CNTs: 0.1%, FA: 40%. Compared with the optimal results for each group, the compressive strength of the final optimized MSFRCC group decreased by 8.9%, the flexural strength increased by 28.4%, the splitting tensile strength increased by 10%, and the chloride ion permeability coefficient decreased by 5.7%. The results show that the compressive performance and resistance to chloride ion penetration of the optimized group are slightly worse than those of the optimal group in the orthogonal test, but its flexural performance and splitting tensile performance are significantly improved.

Characterization of metabolism-associated molecular patterns in prostate cancer.

BACKGROUND: Metabolism is a hallmark of cancer and it involves in resistance to antitumor treatment. Therefore, the purposes of this study are to classify metabolism-related molecular pattern and to explore the molecular and tumor microenvironment characteristics for prognosis predicting in prostate cancer. METHODS: The mRNA expression profiles and the corresponding clinical information for prostate cancer patients from TCGA, cBioPortal, and GEO databases. Samples were classified using unsupervised non-negative matrix factorization (NMF) clustering based on differentially expressed metabolism-related genes (MAGs). The characteristics of disease-free survival (DFS), clinicopathological characteristics, pathways, TME, immune cell infiltration, response to immunotherapy, and sensitivity to chemotherapy between subclusters were explored. A prognostic signature was constructed by LASSO cox regression analysis based on differentially expressed MAGs and followed by the development for prognostic prediction. RESULTS: A total of 76 MAGs between prostate cancer samples and non-tumorous samples were found, then 489 patients were divided into two metabolism-related subclusters for prostate cancer. The significant differences in clinical characteristics (age, T/N stage, Gleason) and DFS between two subclusters. Cluster 1 was associated with cell cycle and metabolism-related pathways, and epithelial-mesenchymal transition (EMT), etc., involved in cluster 2. Moreover, lower ESTIMATE/immune/stromal scores, lower expression of HLAs and immune checkpoint-related genes, and lower half-maximal inhibitory concentration (IC50) values in cluster 1 compared with cluster 2. The 10 MAG signature was identified and constructed a risk model for DFS predicting. The patients with high-risk scores showed poorer DFS. The area under the curve (AUC) values for 1-, 3-, 5-year DFS were 0.744, 0.731, 0.735 in TCGA-PRAD dataset, and 0.668, 0.712, 0.809 in GSE70768 dataset, 0.763, 0.802, 0.772 in GSE70769 dataset. Besides, risk score and Gleason score were identified as independent factors for DFS predicting, and the AUC values of risk score and Gleason score were respectively 0.743 and 0.738. The nomogram showed a favorable performance in DFS predicting. CONCLUSION: Our data identified two metabolism-related molecular subclusters for prostate cancer that were distinctly characterized in prostate cancer. Metabolism-related risk profiles were also constructed for prognostic prediction.

MOF-derived bimetallic nanozyme to catalyze ROS scavenging for protection of myocardial injury.

Rationale: Myocardial injury triggers intense oxidative stress, inflammatory response, and cytokine release, which are essential for myocardial repair and remodeling. Excess reactive oxygen species (ROS) scavenging and inflammation elimination have long been considered to reverse myocardial injuries. However, the efficacy of traditional treatments (antioxidant, anti-inflammatory drugs and natural enzymes) is still poor due to their intrinsic defects such as unfavorable pharmacokinetics and bioavailability, low biological stability, and potential side effects. Nanozyme represents a candidate to effectively modulate redox homeostasis for the treatment of ROS related inflammation diseases. Methods: We develop an integrated bimetallic nanozyme derived from metal-organic framework (MOF) to eliminate ROS and alleviate inflammation. The bimetallic nanozyme (Cu-TCPP-Mn) is synthesized by embedding manganese and copper into the porphyrin followed by sonication, which could mimic the cascade activities of superoxide dismutase (SOD) and catalase (CAT) to transform oxygen radicals to hydrogen peroxide, followed by the catalysis of hydrogen peroxide into oxygen and water. Enzyme kinetic analysis and oxygen-production velocities analysis were performed to evaluate the enzymatic activities of Cu-TCPP-Mn. We also established myocardial infarction (MI) and myocardial ischemia-reperfusion (I/R) injury animal models to verify the ROS scavenging and anti-inflammation effect of Cu-TCPP-Mn. Results: As demonstrated by kinetic analysis and oxygen-production velocities analysis, Cu-TCPP-Mn nanozyme possesses good performance in both SOD- and CAT-like activities to achieve synergistic ROS scavenging effect and provide protection for myocardial injury. In both MI and I/R injury animal models, this bimetallic nanozyme represents a promising and reliable technology to protect the heart tissue from oxidative stress and inflammation-induced injury, and enables the myocardial function to recover from otherwise severe damage. Conclusions: This research provides a facile and applicable method to develop a bimetallic MOF nanozyme, which represents a promising alternative to the treatment of myocardial injuries.

Activatable NIR-II Photothermal Lipid Nanoparticles for Improved Messenger RNA Delivery.

Endosomal escape remains a central issue limiting the high protein expression of mRNA therapeutics. Here, we present second near-infrared (NIR-II) lipid nanoparticles (LNPs) containing pH activatable NIR-II dye conjugated lipid (Cy-lipid) for potentiating mRNA delivery efficiency via a stimulus-responsive photothermal-promoted endosomal escape delivery (SPEED) strategy. In acidic endosomal microenvironment, Cy-lipid is protonated and turns on NIR-II absorption for light-to-heat transduction mediated by 1064 nm laser irradiation. Then, the heat-promoted LNPs morphology change triggers rapid escape of NIR-II LNPs from the endosome, allowing about 3-fold enhancement of enhanced green fluorescent protein (eGFP) encoding mRNA translation capacity compared to the NIR-II light free group. In addition, the bioluminescence intensity induced by delivered luciferase encoding mRNA in the mouse liver region shows positive correlation with incremental radiation dose, indicating the validity of the SPEED strategy.

Materials engineering strategies for cancer vaccine adjuvant development.

Cancer vaccines have emerged as a powerful new tool for cancer immunotherapy. Adjuvants are vaccine ingredients that enhance the strength, velocity, and duration of the immune response. The success of adjuvants in achieving stable, safe, and immunogenic cancer vaccines has generated enthusiasm for adjuvant development. Specifically, advances in materials science are providing insights into the rational design of vaccine adjuvants for topical cancer immunotherapy. Here, we outline the current state of materials engineering strategies, including those based on molecular adjuvants, polymers/lipids, inorganic nanoparticles, and bio-derived materials, for adjuvant development. We also elaborate on how these engineering strategies and the physicochemical features of the materials involved influence the effects of adjuvants.

Engineered Toll-like Receptor Nanoagonist Binding to Extracellular Matrix Elicits Safe and Robust Antitumor Immunity.

Cancer immunotherapy, such as the Toll-like receptor (TLR) agonist including CpG oligodeoxynucleotide, has shown potency in clinical settings. However, it is still confronted with multiple challenges, which include the limited efficacy and severe adverse events caused by the rapid clearance and systemic diffusion of CpG. Here we report an improved CpG-based immunotherapy approach composed of a synthetic extracellular matrix (ECM)-anchored DNA/peptide hybrid nanoagonist (EaCpG) via (1) a tailor designed DNA template that encodes tetramer CpG and additional short DNA moieties, (2) generation of elongated multimeric CpG through rolling circle amplification (RCA), (3) self-assembly of densely packaged CpG particles composed of tandem CpG building blocks and magnesium pyrophosphate, and (4) incorporation of multiple copies of ECM binding peptide through hybridization to short DNA moieties. The structurally well-defined EaCpG shows dramatically increased intratumoral retention and marginal systemic dissemination through peritumoral administration, leading to potent antitumor immune response and subsequent tumor elimination, with minimal treatment-related toxicity. Combined with conventional standard-of-care therapies, peritumor administration of EaCpG generates systemic immune responses that lead to a curative abscopal effect on distant untreated tumors in multiple cancer models, which is superior to the unmodified CpG. Taken together, EaCpG provides a facile and generalizable strategy to simultaneously potentiate the potency and safety of CpG for combinational cancer immunotherapies.

Diagnostic and therapeutic value of biomarkers in urosepsis.

Urosepsis is sepsis caused by urogenital tract infection and is one of the most common critical illnesses in urology. If urosepsis is not diagnosed early, it can rapidly progress and worsen, leading to increased mortality. In recent years, with the increase of urinary tract surgery, the incidence of urosepsis continues to rise, posing a serious threat to patients. Early diagnosis of urosepsis, timely and effective treatment can greatly reduce the mortality of patients. Biomarkers such as WBC, NLR, PCT, IL-6, CRP, lactate, and LncRNA all play specific roles in the early diagnosis or prognosis of urosepsis. In addition to the abnormal increase of WBC, we should be more alert to the rapid decline of WBC. NLR values were superior to WBC counts alone in predicting infection severity. Compared with several other biomarkers, PCT values can differentiate between bacterial and non-bacterial sepsis. IL-6 always has high sensitivity and specificity for the diagnosis of sepsis, and CRP also has high sensitivity and specificity for the diagnosis of urosepsis. Lactic acid is closely related to the prognosis of patients with urosepsis. LncRNAs may be potential biomarkers of urosepsis. This article summarizes the main biomarkers, hoping to provide a reference for the timely diagnosis and evaluation of urosepsis.

N6-methyladenosine-related lncRNAs in combination with computational histopathology and radiomics predict the prognosis of bladder cancer.

OBJECTIVES: Identification of m6A- related lncRNAs associated with BC diagnosis and prognosis. METHODS: From the TCGA database, we obtained transcriptome data and corresponding clinical information (including histopathological and CT imaging data) for 408 patients. And bioinformatics, computational histopathology, and radiomics were used to identify and analyze diagnostic and prognostic biomarkers of m6A-related lncRNAs in BC. RESULTS: 3 significantly high-expressed m6A-related lncRNAs were significantly associated with the prognosis of BC. The BC samples were divided into two subgroups based on the expression of the 3 lncRNAs. The overall survival of patients in cluster 2 was significantly lower than that in cluster 1. The immune landscape results showed that the expression of PD-L1, T cells follicular helper, NK cells resting, and mast cells activated in cluster 2 were significantly higher, and naive B cells, plasma cells, T cells regulatory (Tregs), and mast cells resting were significantly lower. Computational histopathology results showed a significantly higher percentage of tumor-infiltrating lymphocytes (TILs) in cluster 2. The radiomics results show that the 3 eigenvalues of diagnostics image-original minimum, diagnostics image-original maximum, and original GLCM inverse variance are significantly higher in cluster 2. High expression of 2 bridge genes in the PPI network of 30 key immune genes predicts poorer disease-free survival, while immunohistochemistry showed that their expression levels were significantly higher in high-grade BC than in low-grade BC and normal tissue. CONCLUSION: Based on the results of immune landscape, computational histopathology, and radiomics, these 3 m6A-related lncRNAs may be diagnostic and prognostic biomarkers for BC.

Comparison of Transperitoneal and Retroperitoneal Laparoscopic Ureterolithotomy: A Meta-Analysis.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of transperitoneal and retroperitoneal laparoscopic ureterolithotomy (TLU and RLU). MATERIALS AND METHODS: We undertook a literature search PubMed, Embase, and the Cochrane Library. Search date will range from inception to January 1, 2020. The final article results will be analyzed using StataSE 12 software. This meta-analysis was reported according to PRISMA guidelines, and a protocol was registered in PROSPERO (CRD42020160906). RESULTS: Eleven articles eventually met the requirements, involving a total of 609 patients. The final result shows the operative time (Std. Mean Difference [SMD] = 0.58; 95% CI 0.36-0.80; p < 0.01), hospital stay (SMD = 0.26; 95% CI 0.02-0.49; p = 0.031), and the complication of paralytic ileus (risk difference = 0.11; 95% CI 0.05-0.17; p < 0.01) are significant difference between TLU and RLU, and TLU are higher or longer. CONCLUSIONS: Our meta-analysis suggests that if there are no other constraints, it is better to choose RLU. And more clinical trial data are needed to confirm this conclusion.

Osteopontin: An important protein in the formation of kidney stones.

The incidence of kidney stones averages 10%, and the recurrence rate of kidney stones is approximately 10% at 1 year, 35% at 5 years, 50% at 10 years, and 75% at 20 years. However, there is currently a lack of good medicines for the prevention and treatment of kidney stones. Osteopontin (OPN) is an important protein in kidney stone formation, but its role is controversial, with some studies suggesting that it inhibits stone formation, while other studies suggest that it can promote stone formation. OPN is a highly phosphorylated protein, and with the deepening of research, there is growing evidence that it promotes stone formation, and the phosphorylated protein is believed to have adhesion effect, promote stone aggregation and nucleation. In addition, OPN is closely related to immune cell infiltration, such as OPN as a pro-inflammatory factor, which can activate mast cells (degranulate to release various inflammatory factors), macrophages (differentiated into M1 macrophages), and T cells (differentiated into T1 cells) etc., and these inflammatory cells play a role in kidney damage and stone formation. In short, OPN mainly exists in the phosphorylated form in kidney stones, plays an important role in the formation of stones, and may be an important target for drug therapy of kidney stones.

Down-regulation of NOTCH1 and PKM2 can inhibit the growth and metastasis of colorectal cancer cells.

BACKGROUND: Previous studies have revealed the overexpression of Notch receptor 1 (NOTCH1) and pyruvate kinase M2 (PKM2) in colorectal cancer (CRC) tissue and their relationship to disease development. However, whether there is synergy between PKM2 and NOTCH1 needs to be verified. This study aims to analyze the mechanism and relationship between NOTCH1 and PKM2 in CRC. METHODS: Immunohistochemistry was used to measure the expression of NOTCH1 and PKM2 in colorectal cancer, and the correlation between them was analyzed by Pearson test. The protein and mRNA expressions in CRC cell lines were determined by western blot (WB) and real-time quantitative reverse transcription PCR (qRT-PCR). Compound 3K and tangeretin (TGN) were used to inhibit the expressions of PKM2 and NOTCH1, respectively. The wound healing assay and CCK-8 assay were applied to measure the migration and proliferation of cancer cells. RESULTS: Immunohistochemical analysis showed that NOTCH1 and PKM2 were overexpressed in patients with colorectal cancer, and patients with overexpression showed a higher number of lymph node metastases and high tumor stage (III+IV) (P<0.05). In addition, Pearson test showed that the level of NOTCH1 was positively correlated with the level of PKM2 (P<0.05). WB and qRT-PCR showed that the protein and mRNA levels of NOTCH1 and PKM2 in colorectal cancer cells were significantly up-regulated (P<0.05). The inhibition of PKM2 and NOTCH1 had a synergistic effect on reducing the invasion and proliferation of CRC cells. CONCLUSION: NOTCH1 and PKM2 are highly expressed in CRC patients. Inhibiting the expression of NOTCH1 and PKM2 can inhibit the growth and metastasis of CRC cells, providing therapeutic targets for the treatment of CRC.