Metabolic reprogramming in the tumor microenvironment is closely associated with tumor initiation and progression.Endogenous metabolites can not only regulate tumor formation and metastasis,but also impair antitumor immune efficacy by influencing immune cells.However,current research focuses on the effects of single metabolites on tumors rather than take into account the systemic nature of metabolic networks,the diversity of metabolic products,and their dynamic regulatory roles in the tumor immune microenvironment.An in-depth analysis of the key nodes in metabolic pathways related to endogenous metabolites and their regulatory mechanisms in tumor progression is crucial to the development of antitumor therapies based on metabolic intervention.This paper provides an overview of the molecular mechanisms by which endogenous metabolites,such as amino acids,lipids and nucleotides,contribute to tumor progression and regulate the immune microenvironment.By offering new theoretical insights into the complex network of the metabolism-immune axis in tumor development,this review aims to provide data for the development of metabolism-targeted antitumor immuno-therapy strategies.

Asarum forbesii is a perennial herb born in a shaded and humid environment, which is warm in nature. With the efficacy of warming lung, resolving fluid retention, and relieving coughs, it can be used to treat the syndrome of cold fluid accumulating in lung. To investigate the effects of different shading conditions on the composition and efficacy of A. forbesii, this study planted A. forbesii under 20% natural light(NL20), 40% natural light(NL40), 60% natural light(NL60), and 80% natural light(NL80) and utilized ultra performance liquid chromatography(UPLC) and micro broth 2-fold dilution method to detect the volatile chemical compounds and the minimum inhibitory concentration. At the same time, the study investigated the effects of A. forbesii grown under different shading conditions on the signs, pathological changes of lung tissues, serum cytokine levels, activities of mitochondrial respiratory chain complexes Ⅰ-Ⅴ in lung tissues, and relative expression of related genes of mice with syndrome of cold fluid accumulating in lung. The results indicated that with the increase of shading, the content of kakuol, methyl eugenol, and asarinin in A. forbesii and the antibacterial effect showed a tendency of increasing first and then decreasing, and the NL40 group was significantly better than the other groups. Under the conditions of NL20 and NL40, A. forbesii significantly alleviated the pathological damage to lung tissues, restored the homeostasis of the lung, and enhanced the energy metabolism level of mice with syndrome of cold fluid accumulating in lung. In addition, A. forbesii planted under the two conditions reduced the content of interleukin-8(IL-8), interleukin-13(IL-13), tumor necrosis factor-α(TNF-α), and mucin 5AC(MUC5AC), increased the levels of interleukin-10(IL-10) and aquaporin 1(AQP1), lowered the expression of MMP9, VEGF, TGF-β, and MAPK3. In conclusion, the therapeutic effect of A. forbesii on the syndrome of cold fluid accumulating in lung was positively correlated with the degree of shading, and the chemical composition and efficacy of warming lung and resolving fluid retention were optimal under the conditions of NL20-NL40. This study can provide reference for the pharmacological research and cultivation of A. forbesii.
Animals ; Mice ; Lung/pathology* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Light ; Cytokines/genetics* ; Humans

The ocean plays a critical role in the global carbon cycle,and base on the"dual carbon"goals,ocean carbon sinks have received widespread attention.Shellfish aquaculture is one of the most important sources of carbon sinks in fisheries,which has an important impact on the offshore carbon cy-cle.As global temperature rises and ocean acidification intensifies,the capacity of the ocean to absorb CO2 will change.However,the effects of high temperature on the physiology and transcriptome related to carbon metabolism in Mytilus coruscus are not clear enough.This study investigated the effects of high temperatures on the total carbon content,carbon metabolism,antioxidant-related enzyme activities,and the transcriptome of Mytilus coruscus.The results showed that high temperature significantly inhibited the activities of hexokinase and pyruvate kinase,increased carbonic anhydrase activity(P＜0.05),de-creased the ATP content of digestive glands(P＜0.05),and affected glycolysis and the tricarboxylic acid cycle,leading to a significant decrease in the mussel's ability to sequester carbon.High temperature re-sulted in significant(P＜0.05)increases in the levels of reactive oxygen species and malondialdehyde,and enhanced the activities of superoxide dismutase and catalase.Observations by transmission electron microscopy showed that high temperatures damaged the subcellular structure of the digestive gland in Mytilus coruscus,resulting in the shrinkage of the nucleolus,swelling of the endoplasmic reticulum,and a significant reduction in the mitochondrial cristae.Comparative transcriptomic analysis showed that the upregulated DEGs were mainly enriched in protein processing in the endoplasmic reticulum,antigen pro-cessing and presentation,and MAPK signaling pathway.The downregulated DEGs were mainly enriched in necroptosis,DNA replication,and the NF-kappa B signaling pathway.In antioxidant-related DEGs,the upregulated DEGs include vitamin K epoxide reductase,peroxidases,heat shock protein 105 kD,heat shock protein 70 kD,and superoxide dismutase;The downregulated DEGs mainly included NADPH oxidase,glutathione reductase,cytochrome b-245,cytochrome P450,and quinone reductase.The up-regulated genes enriched in the carbon metabolism pathway included chitinase,phosphatidylinositol 4,5-bisphosphate 3-kinase,phosphoenolpyruvate carboxykinase,galactokinase,and inositol trisphosphate 3-kinase.The downregulated genes included aldose-1-epimerase,carbonic anhydrase,galactose mutaro-tase,acyl-CoA synthetase,alcohol dehydrogenase,and hexokinase.In conclusion,high temperature has an inhibitory effect on the activities of enzymes and the expression of genes related to carbon metabolism in Mytilus coruscus.The results of this study are intended to provide a scientific basis for the healthy de-velopment of mussel aquaculture and the assessment of carbon sinks.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

The ocean plays a critical role in the global carbon cycle,and base on the"dual carbon"goals,ocean carbon sinks have received widespread attention.Shellfish aquaculture is one of the most important sources of carbon sinks in fisheries,which has an important impact on the offshore carbon cy-cle.As global temperature rises and ocean acidification intensifies,the capacity of the ocean to absorb CO2 will change.However,the effects of high temperature on the physiology and transcriptome related to carbon metabolism in Mytilus coruscus are not clear enough.This study investigated the effects of high temperatures on the total carbon content,carbon metabolism,antioxidant-related enzyme activities,and the transcriptome of Mytilus coruscus.The results showed that high temperature significantly inhibited the activities of hexokinase and pyruvate kinase,increased carbonic anhydrase activity(P＜0.05),de-creased the ATP content of digestive glands(P＜0.05),and affected glycolysis and the tricarboxylic acid cycle,leading to a significant decrease in the mussel's ability to sequester carbon.High temperature re-sulted in significant(P＜0.05)increases in the levels of reactive oxygen species and malondialdehyde,and enhanced the activities of superoxide dismutase and catalase.Observations by transmission electron microscopy showed that high temperatures damaged the subcellular structure of the digestive gland in Mytilus coruscus,resulting in the shrinkage of the nucleolus,swelling of the endoplasmic reticulum,and a significant reduction in the mitochondrial cristae.Comparative transcriptomic analysis showed that the upregulated DEGs were mainly enriched in protein processing in the endoplasmic reticulum,antigen pro-cessing and presentation,and MAPK signaling pathway.The downregulated DEGs were mainly enriched in necroptosis,DNA replication,and the NF-kappa B signaling pathway.In antioxidant-related DEGs,the upregulated DEGs include vitamin K epoxide reductase,peroxidases,heat shock protein 105 kD,heat shock protein 70 kD,and superoxide dismutase;The downregulated DEGs mainly included NADPH oxidase,glutathione reductase,cytochrome b-245,cytochrome P450,and quinone reductase.The up-regulated genes enriched in the carbon metabolism pathway included chitinase,phosphatidylinositol 4,5-bisphosphate 3-kinase,phosphoenolpyruvate carboxykinase,galactokinase,and inositol trisphosphate 3-kinase.The downregulated genes included aldose-1-epimerase,carbonic anhydrase,galactose mutaro-tase,acyl-CoA synthetase,alcohol dehydrogenase,and hexokinase.In conclusion,high temperature has an inhibitory effect on the activities of enzymes and the expression of genes related to carbon metabolism in Mytilus coruscus.The results of this study are intended to provide a scientific basis for the healthy de-velopment of mussel aquaculture and the assessment of carbon sinks.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

This study aimed to investigate the mechanism by which Shegan Mahuang Decoction(SGMH) and its bitter Chinese herbs(BCHs) regulated the lung-gut axis through the bitter taste receptor 14(TAS2R14)/secretory immunoglobulin A(SIgA)/thymic stromal lymphopoietin(TSLP) to intervene in the epithelial cell barrier of cold asthma rats. Fifty SD rats were randomly divided into the following five groups: normal group, model group, dexamethasone group, SGMH group, and BCHs group. A 10% ovalbumin(OVA) solution was used to sensitize the rats via subcutaneous injection on both sides of the abdomen and groin, combined with 2% OVA atomization and cold(2-4 ℃) stimulation to induce a cold asthma model in rats. The SGMH, BCHs, and dexamethasone groups were given corresponding treatments by gavage and nebulization, while the normal and model groups received normal saline by gavage and nebulization. After the final stimulation, pathological changes in the lung and intestine tissues were observed using hematoxylin-eosin(HE) and periodic acid-Schiff(PAS) staining. Lung function was assessed by measuring the ratio of forced expiratory volume in the first second to forced vital capacity(FEV1/FVC), the ratio of the average flow rate at 25%-75% of forced vital capacity to foned vital capacity(FEV25%-75%/FVC), the peak expiratory flow(PEF), and pulmonary resistance(RL). The levels of IL-4, IL-5, IL-13, and TNF-α in serum, and sIgA in serum, intestinal, and bronchial mucosa were detected by enzyme-linked immunosorbent assay(ELISA). The expression of TAS2R14 protein in lung tissue was detected by Western blot(WB). The content of short-chain fatty acids(SCFAs) in rat feces was determined by gas chromatography-mass spectrometry(GC-MS). The effect of TAS2R14/TSLP on lipopolysaccharide(LPS)-induced inflammation in epithelial cells in the BCHs group was observed, and the expression of TAS2R14 and TSLP in cells was detected by WB. Compared with the normal group, the model group showed reduced water intake, diet, and body weight, increased infiltration of inflammatory cells in the lung and intestinal tissues, goblet cell hyperplasia, significantly decreased FEV1/FVC, FEV25%-75%/FVC, and PEF, and significantly increased RL. Moreover, serum levels of IL-4, IL-5, IL-13, and TNF-α were elevated, and sIgA levels in serum, intestine, and bronchial mucosa were significantly decreased. TAS2R14 expression in lung tissues was inhibited, and the content of acetic acid, propionic acid, and butyric acid in feces was significantly reduced. In the LPS group, TSLP expression increased, and TAS2R14 expression decreased. Compared with the model group, the general condition of rats in the SGMH and BCHs groups improved, with reduced infiltration of inflammatory cells and goblet cell hyperplasia in the lung and intestinal tissues. FEV1/FVC, FEV25%-75%/FVC, and PEF significantly increased, and RL significantly decreased. Serum levels of IL-4, IL-5, IL-13, and TNF-α decreased, while sIgA levels in serum, intestine, and bronchial mucosa significantly increased, and TAS2R14 expression was activated in lung and intestinal tissues. The content of acetic acid, propionic acid, and butyric acid in feces significantly increased. Compared with the model group, the BCHs group and the agonist group showed inhibited TSLP expression and increased TAS2R14 expression. The results showed that both SGMH and BCHs could reduce lung and intestinal inflammatory reactions, improve lung function, and regulate the content of intestinal SCFAs in asthmatic rats. There was no significant difference in TAS2R14 protein expression between the SGMH and BCHs groups, indicating that the clinical efficacy of BCHs may be related to the activation of the bitter receptor TAS2R14 and the regulation of immune inflammatory mediators in lung and intestinal epithelial cells.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Rats, Sprague-Dawley ; Lung/metabolism* ; Asthma/metabolism* ; Cytokines/immunology* ; Male ; Receptors, G-Protein-Coupled/immunology* ; Epithelial Cells/metabolism* ; Thymic Stromal Lymphopoietin ; Immunoglobulin A, Secretory/genetics* ; Humans ; Cold Temperature

Liver metastasis is a key factor impacting the treatment outcomes and survival prognoses of patients with colorectal cancer(CRC).In recent years,immunotherapy has demonstrated revolutionary potential in the treatment of a wide range of solid tumors by strengthen-ing the host's antitumor immune response and has become a mainstream option for the treatment of metastatic or recurrent solid tumors.Immune checkpoint inhibitor-based immunotherapy,in particular,has shown promising advances in safety and efficacy in CRC treatment,especially for deficient mismatch repair(dMMR)CRC.Despite these advances,patients with liver metastases have not seen any improvements in their survival prognoses.In this article,we comprehensively review immunotherapeutic strategies for treating liver metastases from CRC,discuss the efficacy of each strategy,and provide an in-depth discussion of prospective future directions.

Liver metastasis is a key factor impacting the treatment outcomes and survival prognoses of patients with colorectal cancer(CRC).In recent years,immunotherapy has demonstrated revolutionary potential in the treatment of a wide range of solid tumors by strengthen-ing the host's antitumor immune response and has become a mainstream option for the treatment of metastatic or recurrent solid tumors.Immune checkpoint inhibitor-based immunotherapy,in particular,has shown promising advances in safety and efficacy in CRC treatment,especially for deficient mismatch repair(dMMR)CRC.Despite these advances,patients with liver metastases have not seen any improvements in their survival prognoses.In this article,we comprehensively review immunotherapeutic strategies for treating liver metastases from CRC,discuss the efficacy of each strategy,and provide an in-depth discussion of prospective future directions.

OBJECTIVE: To assess whether the use of Tanreqing (TRQ) Injection could show improvements in time to extubation, intensive care unit (ICU) mortality, ventilator-associated events (VAEs) and infection-related ventilator associated complication (IVAC) among patients receiving mechanical ventilation (MV). METHODS: A time-dependent cox-regression analysis was conducted using data from a well-established registry of healthcare-associated infections at ICUs in China. Patients receiving continuous MV for 3 days or more were included. A time-varying exposure definition was used for TRQ Injection, which were recorded on daily basis. The outcomes included time to extubation, ICU mortality, VAEs and IVAC. Time-dependent Cox models were used to compare the clinical outcomes between TRQ Injection and non-use, after controlling for the influence of comorbidities/conditions and other medications with both fixed and time-varying covariates. For the analyses of time to extubation and ICU mortality, Fine-Gray competing risk models were also used to measure competing risks and outcomes of interest. RESULTS: Overall, 7,685 patients were included for the analyses of MV duration, and 7,273 patients for the analysis of ICU mortality. Compared to non-use, patients with TRQ Injection had a lower risk of ICU mortality (Hazards ratios (HR) 0.761, 95% CI, 0.581-0.997), and was associated with a higher hazard for time to extubation (HR 1.105, 95% CI, 1.005-1.216), suggesting a beneficial effect on shortened time to extubation. No significant differences were observed between TRQ Injection and non-use regarding VAEs (HR 1.057, 95% CI, 0.912-1.225) and IVAC (HR 1.177, 95% CI, 0.929-1.491). The effect estimates were robust when using alternative statistic models, applying alternative inclusion and exclusion criteria, and handling missing data by alternative approaches. CONCLUSION Our findings suggested that the use of TRQ Injection might lower mortality and improve time to extubation among patients receiving MV, even after controlling for the factor that the use of TRQ changed over time.
Humans ; Respiration, Artificial/adverse effects* ; Intensive Care Units ; Proportional Hazards Models ; Registries ; Length of Stay