Colorectal cancer (CRC) is characterized by persistently high incidence and mortality. Current therapies are limited by drug resistance and modest patient benefit, underscoring the urgent need for new perspectives rooted in tumor biology. The unique metabolic landscape of CRC makes it an ideal model in which to dissect the pathological roles of lactylation regulatory networks: microsatellite-stable (MSS) CRC, which accounts for approximately 85% of cases, concurrently upregulates glycolysis and oxidative phosphorylation, engaging in intense metabolic competition with immune cells; the intratumoral lactate pool exhibits a distinctive “dual-source supply” feature—in addition to tumor-intrinsic glycolysis, substantial exogenous lactate is provided by gut microbiota dysbiosis and by colonizing bacteria within liver metastases; high-frequency oncogenic mutations and lactylation modifications establish a feed-forward circuit of “oncogene-driven lactate accumulation-lactylation-facilitated tumor progression”. Moreover, MSS CRC displays near-complete unresponsiveness to immune checkpoint inhibitors, a phenomenon underpinned by multiple immune evasion mechanisms mediated by lactate and lactylation. Lactate metabolism is a hallmark of metabolic reprogramming in cancer. Lactate homeostasis provides tumor cells with metabolic substrates, modulates redox status, and regulates fatty acid metabolism to promote malignant progression. Notably, lactate can drive lactylation—an emerging post-translational modification (PTM) in which lactyl groups are attached to lysine residues, dynamically governing gene transcription and protein function and thereby establishing a bridge between metabolism and epigenetics. Lactate and lactylation form a multidimensional, coordinated network: lactylation of key metabolic enzymes such as LDHA reinforces a positive feedback loop that sustains lactate production; lactylation of upstream transcription factors such as HIF-1α drives metabolic reprogramming; furthermore, lactylation engages in crosstalk with m6A and m5C RNA modifications as well as with other PTMs such as acetylation, profoundly reshaping cellular behavior. In CRC, histone lactylation drives malignant phenotypes by activating immunosuppressive programs, inhibiting ferroptosis, and promoting invasion and migration; non-histone lactylation accelerates translation elongation, stabilizes β‑catenin, maintains redox homeostasis, and prevents PD-L1 degradation, thereby facilitating tumor progression. Lactylation-related gene signatures have demonstrated potential for prognostic stratification. Therapeutic strategies targeting the lactylation network range from upstream metabolic intervention to modulation of the modifying enzymes and direct blockade of lactylation modifications, forming a hierarchical interventional framework. However, current evidence derives predominantly from cell lines and xenograft models, and a causal relationship between lactylation and malignant progression in CRC has yet to be rigorously established. Whether inhibition of lactylation can alter CRC phenotypes independently of metabolic alterations and acetylation fluctuations remains a central unanswered question in the field. This review systematically examines the research progress and translational challenges surrounding lactylation regulatory networks, aiming to provide a circumspect assessment to inform the development of novel therapeutic strategies for CRC.

AIM:To investigate the risk factors for intolerance to sacubitril/valsartan in the treatment of heart failure.METHODS:A total of 124 heart fail-ure patients hospitalized in our hospital from May 2023 to May 2024 were collected.Logistic regres-sion analysis and nomogram analysis were used to identify the risk factors for drug tolerance.RE-SULTS:22 patients exhibited intolerance,with low blood pressure being the primary cause(P<0.05).Multivariate regression analysis found that patients with a low BMI(OR 95%CI 1.814(1.385-2.525))and those without concomitant right heart failure(OR 95%CI 4.998(1.552-17.301))were more likely to ex-perience drug intolerance.The model had a stable C-index of 0.923(95%CI=0.863-0.975).CONCLU-SION:Low BMI and absence of right heart failure are risk factors affecting the tolerance to sacubitril/valsartan,which has certain value for guiding clini-cal treatment.Large-sample clinical studies are still needed to confirm these findings.

Porcine hemagglutinating encephalomyelitis virus(PHEV)is one of the coronaviruses susceptible to swine populations.The non-structural protein 2(NS2)encoded by its genome is fre-quently deleted during the epidemic transmission of the virus,but its biological significance re-mains unclear.In order to explore the structure and function of the NS2 protein,this study utilized platforms such as ProtParam,TMHMM,NetPhos3.1,and ExPASy to analyze its physicochemical properties,spatial structure,genetic evolution,and post-translational modification characteristics.Meanwhile,the NS2 protein was expressed in eukaryotes and transcriptome sequencing was per-formed to clarify the biological processes it participates in.The results showed that the NS2 protein consists of 233 amino acids,with a molecular weight of 26.735 kDa,and a half-life of approximately 30 hours in mammals.It includes 13 phosphorylation sites,2 N-glycosylation sites,and 1 O-glyco-sylation site,with no signal peptide and strong hydrophilicity.The a-helix accounts for the highest proportion in NS2(43.78％),followed by random coils(36.05％).The homology of the NS2 pro-tein between the epidemic strains PHEV-CC14 and PHEV-JL/2008 in Northeast China is 99.57％.The NS2 protein is widely involved in the regulation of nerve-related functions,such as axon guid-ance and synaptic development.This study preliminarily clarified the biological function of the NS2 protein,providing a new perspective for understanding the pathogenic mechanism of PHEV.

Objective To investigate the electroencephalography(EEG)signal characteristics in patients with neuropathic pain(NP)associated with spinal cord injury(SCI).Methods A total of 90 patients with SCI from January,2018 to November,2023 were selected from the EEG database of the Department of Rehabilitation Medicine,Xijing Hospital,and divided into NP group(n=46)and non-NP group(n=44)according to their symptoms.The resting-state EEG power and reactivity to eye-opening were compared between two groups.Results Compared with non-NP group,EEG power increased in frontal lobe in α and β1 bands,central lobe in δ,θ,α1 and β1 bands,parietal lobe in α and β1 bands,temporal lobe in α and β1 bands,left occipital lobe in α2 band,and occipital lobe in α1 and β1 bands(|Z|>1.998,P<0.05)in NP group during eye-opening;during eye-closing,EEG power increased in prefrontal lobe in α1 and β1 bands,right frontal lobe in θ band,frontal lobe in α and β1 bands,left frontal lobe in β2 band,central lobe in δ,α1 and β1 bands,parietal lobe in α1 and β1 bands,left pari-etal lobe in α2 and β2 bands,right temporal lobe in θ band,temporal lobe in α and β bands,occipital lobe in α1 and β1 bands,and left occipital lobe in β2 band(|Z|>1.970,P<0.05);while the reactivity to eye-opening de-creased in right prefrontal lobe in β1 band,frontal lobe in θ,α and β bands,right central lobe in β1 band,parietal lobe in α1 and β1 bands,right parietal lobe in β2 band,right temporal lobe in δ and θ band,temporal lobe in α1 and β bands,left occipital lobe in α1 band,and occipital lobe in β1(|Z|>1.967,P<0.05).Conclusion Resting-state EEG power characteristically elevates in NP patients after SCI,and the reactivity to eye-open-ing reduces.

Paclitaxel(PTX)is a first-line chemotherapy drug for breast cancer,but its resistance issues significantly impact clinical treatment efficacy.Fucosylation,especially core fucosylation,is closely related to tumor chemoresistance,resulting in poor chemotherapy responses and poor prognosis in patients.In this study,we investigated the effect and mechanism of the fucosylation inhibitor 2-fluorofucose(2-F-Fuc)on the chemosensitivity of paclitaxel-resistant breast cancer MCF-7/PTX cells.The drug resistanceindex(RI)of MCF-7/PTX cells was 8.49 by MTT assays.Western blotting,real-time PCR,enzyme-linked immu-nosorbent assay(ELISA)and Lens Culinaris Agglutinin(LCA)lectin imprinting showed that compared with MCF-7 cells,the expression of FUT8,MDR1and core fucosylation in MCF-7/PTX cells was high.Western blotting showed that 2-F-Fuc had a significant inhibitory effect on the growth of MCF-7/PTX cells,and the expression levels of FUT8 and MDR1 were significantly down-regulated after 2-F-Fuc treatment,and the down-regulation was more pronounced in the PTX and 2-F-Fuc combination group(P＜0.05).Compared to the control,expression of PCNA in MCF-7/PTX cells in the PTX and the 2-F-Fuc group were down-regulated,and the apoptosis-related proteins,such as cleaved caspase-3 and Bax/Bcl-2 were in-creased.The level of p-PI3K and p-AKT were down-regulated,and the changes in the combination of 2-F-Fuc and PTX were more robust(P＜0.05).The above results showed that the core fucosylation level of MCF-7/PTX cells was significantly increased,and 2-F-Fuc could reduce the core fucosylation level of MCF-7/PTX cells by inhibiting the expression of FUT8,and enhance the sensitivity of drug-resistant cells to PTX,which may correlate with the downregulation of PI3K/AKT signaling pathway proteins.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Background::Hepatitis B poses a heavy burden for children in China, however, the national studies on the distributional characteristics and health care costs of children with severe hepatitis B is still lacking. This study aimed to analyze the disease characteristics, health economic effects, and medical cost for children with severe hepatitis B in China.Methods::Based on patient information in the Hospital Quality Monitoring System, cases with severe hepatitis B were divided into four groups according to age, and the etiology and symptoms of each group were quantified. The cost of hospitalization was calculated for cases with different disease processes, and severity of disease. The spatial aggregation of cases and the relationship with health economic factors were analyzed by Moran’s I analysis. Results::The total number of children discharged with hepatitis B from January 2016 to April 2022 was 1603, with an average age of 10.5 years. Liver failure cases accounted for 43.48% (697/1603) of total cases and cirrhosis cases accounted for 11.23% (180/1603). According to the grouping of disease progression, there were 1292 cases without associated complications, and the median hospitalization cost was $818.12. According to the spatial analysis, the aggregation of cases was statistically significant at the prefectural and provincial levels in 2019, 2020, and 2021 (all P <0.05). The number of severe cases was negatively correlated with gross domestic product (Moran’s I <0) and percentage of urban population (Moran’s I <0), and positively correlated with the number of pediatric beds per million population (Moran’s I >0). Conclusion::The number of severe hepatitis B cases is low in areas with high gross domestic product levels and high urban population ratios, and health care costs have been declining over the years.

Transcatheter edge-to-edge repair has become the most important and widely recognized method for the treatment of patients with severe mitral regurgitation who are at high risk for surgery.At present,TEER is developing rapidly in China,the operation process tends to be standardized and standardized,and various domestic Clip devices are also constantly developing and improving,but the operation process of this technology is very dependent on the guidance and monitoring of transesophageal echocardiography,and many surgeons often only pay attention to the repair effect of TEER on MR,and ignore the damage of TEE probe to the esophagus.This study reports a case of esophageal erosion occurring in a patient after mitral valve clipping for mitral regurgitation,aiming to enhance awareness among colleagues regarding esophageal injury caused by transesophageal echocardiography probes.

AIM:To investigate the risk factors for intolerance to sacubitril/valsartan in the treatment of heart failure.METHODS:A total of 124 heart fail-ure patients hospitalized in our hospital from May 2023 to May 2024 were collected.Logistic regres-sion analysis and nomogram analysis were used to identify the risk factors for drug tolerance.RE-SULTS:22 patients exhibited intolerance,with low blood pressure being the primary cause(P<0.05).Multivariate regression analysis found that patients with a low BMI(OR 95%CI 1.814(1.385-2.525))and those without concomitant right heart failure(OR 95%CI 4.998(1.552-17.301))were more likely to ex-perience drug intolerance.The model had a stable C-index of 0.923(95%CI=0.863-0.975).CONCLU-SION:Low BMI and absence of right heart failure are risk factors affecting the tolerance to sacubitril/valsartan,which has certain value for guiding clini-cal treatment.Large-sample clinical studies are still needed to confirm these findings.

Objective To investigate the electroencephalography(EEG)signal characteristics in patients with neuropathic pain(NP)associated with spinal cord injury(SCI).Methods A total of 90 patients with SCI from January,2018 to November,2023 were selected from the EEG database of the Department of Rehabilitation Medicine,Xijing Hospital,and divided into NP group(n=46)and non-NP group(n=44)according to their symptoms.The resting-state EEG power and reactivity to eye-opening were compared between two groups.Results Compared with non-NP group,EEG power increased in frontal lobe in α and β1 bands,central lobe in δ,θ,α1 and β1 bands,parietal lobe in α and β1 bands,temporal lobe in α and β1 bands,left occipital lobe in α2 band,and occipital lobe in α1 and β1 bands(|Z|>1.998,P<0.05)in NP group during eye-opening;during eye-closing,EEG power increased in prefrontal lobe in α1 and β1 bands,right frontal lobe in θ band,frontal lobe in α and β1 bands,left frontal lobe in β2 band,central lobe in δ,α1 and β1 bands,parietal lobe in α1 and β1 bands,left pari-etal lobe in α2 and β2 bands,right temporal lobe in θ band,temporal lobe in α and β bands,occipital lobe in α1 and β1 bands,and left occipital lobe in β2 band(|Z|>1.970,P<0.05);while the reactivity to eye-opening de-creased in right prefrontal lobe in β1 band,frontal lobe in θ,α and β bands,right central lobe in β1 band,parietal lobe in α1 and β1 bands,right parietal lobe in β2 band,right temporal lobe in δ and θ band,temporal lobe in α1 and β bands,left occipital lobe in α1 band,and occipital lobe in β1(|Z|>1.967,P<0.05).Conclusion Resting-state EEG power characteristically elevates in NP patients after SCI,and the reactivity to eye-open-ing reduces.