A high-performance liquid chromatography method using pre-column derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate was developed to determine the content of 15 amino acids in the medicinal snakes Bungarus Parvus, Agkistrodon, and Zaocys. The results showed that the total amino acid(TAA) content ranged from 277.13 to 515.05 mg·g~(-1), with the top four amino acids in all three species being glutamic acid(Glu), glycine(Gly), aspartic acid(Asp), and lysine(Lys). The essential amino acid(EAA) content ranged from 74.56 to 203.94 mg·g~(-1), with Agkistrodon exhibiting the highest content. The non-essential amino acid(NEAA), semi-essential amino acid(semi-EAA), and medicinal amino acid(MAA) content ranged from 189.06 to 318.23, 12.89 to 33.53, and 179.83 to 342.33 mg·g~(-1), respectively, with Zaocys having the highest content in these categories. Amino acid nutritional value was evaluated using the amino acid ratio(RAA), amino acid ratio coefficient(RCAA), and amino acid ratio coefficient score(SRCAA), and the results indicated that all three medicinal snakes possessed good nutritional value. The amino acid composition was similar across the species, though significant differences in content were observed. Based on these differences, an orthogonal partial least squares-discriminant analysis(OPLS-DA) model was established, which could clearly distinguish between the three medicinal snake species. The key differences in amino acid content included Gly, tyrosine(Tyr), Glu, and serine(Ser), which may be related to the observed clinical application differences among the species. Further research into the mechanisms of these differential amino acids is expected to provide more insights into the clinical application disparities of these three medicinal snake species.
Amino Acids/chemistry* ; Animals ; Nutritive Value ; Chromatography, High Pressure Liquid ; Snakes/classification* ; Bungarus

The tumor microenvironment is a crucial factor in tumor occurrence and progression. The hypoxic microenvironment is widely present in tumor tissue and is a key endogenous factor accelerating tumor deterioration. The "blood stasis toxin" theory, as an emerging perspective in tumor research, is regarded as the unique "soil" in tumor progression from the perspective of traditional Chinese medicine(TCM) due to its dynamic evolution mechanism, which closely resembles the formation of the hypoxic microenvironment. Scientifically integrating TCM theories with the biological characteristics of tumors and exploring precise syndrome differentiation and treatment strategies are key to achieving comprehensive tumor prevention and control. This article focused on the hypoxic microenvironment of the tumor, elucidating its formation mechanisms and evolutionary processes and carefully analyzing the internal relationship between the "blood stasis toxin" theory and the hypoxic microenvironment. Additionally, it explored the interaction among blood stasis, toxic pathogens, and hypoxic environment and proposed micro-level prevention and treatment strategies targeting the hypoxic microenvironment based on the "blood stasis toxin" theory, aiming to provide TCM-based theoretical support and therapeutic approaches for precise regulation of the hypoxic microenvironment.
Humans ; Tumor Microenvironment/drug effects* ; Neoplasms/therapy* ; Animals ; Medicine, Chinese Traditional ; Disease Progression ; Drugs, Chinese Herbal

BACKGROUND AND OBJECTIVE: Patients with glioma experience a high symptom burden and have diverse palliative care needs. However, the assessment scales used in palliative care remain non-standardized and highly heterogeneous. To evaluate the application patterns of the current scales used in palliative care for glioma, we aim to identify gaps and assess the need for disease-specific scales in glioma palliative care. METHODS: We conducted a systematic search of five databases including PubMed, Web of Science, Medline, EMBASE, and CINAHL for quantitative studies that reported scale-based assessments in glioma palliative care. We extracted data on scale characteristics, domains, frequency, and psychometric properties. Quality assessments were performed using the Cochrane ROB 2.0 and ROBINS-I tools. RESULTS: Of the 3,405 records initially identified, 72 studies were included. These studies contained 75 distinct scales that were used 193 times. Mood (21.7%), quality of life (24.4%), and supportive care needs (5.2%) assessments were the most frequently assessed items, exceeding half of all scale applications. Among the various assessment dimensions, the Distress Thermometer (DT) was the most frequently used tool for assessing mood, while the Short Form-36 Health Survey Questionnaire (SF-36) was the most frequently used tool for assessing quality of life. The Mini Mental Status Examination (MMSE) was the most common tool for cognitive assessment. Performance status (5.2%) and social support (6.8%) were underrepresented. Only three brain tumor-specific scales were identified. Caregiver-focused scales were limited and predominantly burden-oriented. CONCLUSIONS: There are significant heterogeneity, domain imbalances, and validation gaps in the current use of assessment scales for patients with glioma receiving palliative care. The scale selected for use should be comprehensive and user-friendly.
Humans ; Glioma/psychology* ; Palliative Care/methods* ; Quality of Life ; Psychometrics ; Brain Neoplasms/psychology*

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

ObjectiveTo optimize Tusizi prescription for ovarian reserve function based on the uniform design method combined with in vitro experiments and explore the underlying mechanisms of this prescription. MethodsThe uniform design method was adopted to design a 5-factor 11-level experiment on the water extract of Tusizi prescription. The cell-counting kit-8 （CCK-8） assay was employed to measure the viability of human ovarian granulosa cells （KGN cells） treated with Tusizi prescription extracts 1-11， and multivariate regression analysis was performed to determine the optimal herb ratio in this prescription. The potential targets of active ingredients in the prescription were retrieved from traditional Chinese medicine systems pharmacology database and analysis platform （TCMSP） and encyclopedia of traditional Chinese medicine （ETCM）. The common targets shared by Tusizi prescription and diminished ovarian reserve （DOR） were selected and imported into search tool for the retrieval of interacting genes/proteins （STRING） to construct a protein-protein interaction （PPI） network and into gene function annotation database （DAVID） for gene ontology （GO） analysis. The CCK-8 assay was used to measure the viability of ovarian germline stem cells treated with hyperoside. The CCK-8 assay， 5-ethynyl-2'-deoxyuridine （EdU） staining， terminal-deoxynucleoitidyl transferase mediated nick-end labeling （TUNEL）， and enzyme-linked immunosorbent assay （ELISA） were employed to examine the proliferation， apoptosis， and estradiol （E₂） secretion of KGN cells treated with the water extract 11 of Tusizi prescription （Cuscutae Semen-Lycii Fructus-Dioscoreae Rhizoma-Poria-Nelumbinis Semen 4∶4∶2∶1∶1） and the optimal prescription screened by uniform design. On this basis， the optimal prescription composition for maximizing the effect on ovarian reserve function was determined and preliminary insights into the underlying mechanisms of this prescription were gained. ResultsA total of 147 common targets were obtained from 278 targets of Tusizi prescription and 1 721 targets of DOR. GO analysis revealed 194 biological processes， primarily involving cellular responses to exogenous compound stimuli， negative regulation of apoptotic process， and positive regulation of cell proliferation. It identified 84 cellular components， including cell membrane， mitochondria， and neuronal cell body， as well as 144 molecular functions such as enzyme binding， estrogen response element binding， and nuclear estrogen receptor binding. The multivariate regression analysis revealed that when Tusizi prescription was composed of Cuscutae Semen， Lycii Fructus， Dioscoreae Rhizoma， Poria， and Nelumbinis Semen in a ratio of 27∶30∶17∶12∶14， the water extract of Tusizi prescription had the best effect of enhancing the viability of KGN cells. CCK-8 results showed that compared with the normal group， the hyperoside group demonstrated increased viability of ovarian germline stem cells （P<0.01）. The CCK-8， EdU， and ELISA results showed that compared with the normal group， the optimal prescription screened by uniform design and the water extract 11 of Tusizi prescription increased the proliferation and reduced the apoptosis of KGN cells （P<0.05， P<0.01）. ELISA results showed that compared with the normal group， the water extract 11 of Tusizi prescription promoted the E₂ secretion of KGN cells （P<0.05）， while the optimal prescription screened by uniform design had no significant effect on the E₂ secretion. ConclusionBoth the water extract 11 of Tusizi prescription （Cuscutae Semen-Lycii Fructus-Dioscoreae Rhizoma-Poria-Nelumbinis Semen 4∶4∶2∶1∶1） and the optimal prescription screened by uniform design （Cuscutae Semen-Lycii Fructus-Dioscoreae Rhizoma-Poria-Nelumbinis Semen 27∶30∶17∶12∶14） can improve the ovarian reserve function， and the former has better effect. Tusizi prescription can modulate biological processes （such as cell proliferation and apoptosis） and molecular functions （such as enzyme binding and estrogen response element binding） through active components like hyperoside to promote the proliferation and E₂ secretion and inhibit the apoptosis of KGN cells， thereby protecting the ovarian reserve function.

ObjectiveTo optimize Tusizi prescription for ovarian reserve function based on the uniform design method combined with in vitro experiments and explore the underlying mechanisms of this prescription. MethodsThe uniform design method was adopted to design a 5-factor 11-level experiment on the water extract of Tusizi prescription. The cell-counting kit-8 （CCK-8） assay was employed to measure the viability of human ovarian granulosa cells （KGN cells） treated with Tusizi prescription extracts 1-11， and multivariate regression analysis was performed to determine the optimal herb ratio in this prescription. The potential targets of active ingredients in the prescription were retrieved from traditional Chinese medicine systems pharmacology database and analysis platform （TCMSP） and encyclopedia of traditional Chinese medicine （ETCM）. The common targets shared by Tusizi prescription and diminished ovarian reserve （DOR） were selected and imported into search tool for the retrieval of interacting genes/proteins （STRING） to construct a protein-protein interaction （PPI） network and into gene function annotation database （DAVID） for gene ontology （GO） analysis. The CCK-8 assay was used to measure the viability of ovarian germline stem cells treated with hyperoside. The CCK-8 assay， 5-ethynyl-2'-deoxyuridine （EdU） staining， terminal-deoxynucleoitidyl transferase mediated nick-end labeling （TUNEL）， and enzyme-linked immunosorbent assay （ELISA） were employed to examine the proliferation， apoptosis， and estradiol （E₂） secretion of KGN cells treated with the water extract 11 of Tusizi prescription （Cuscutae Semen-Lycii Fructus-Dioscoreae Rhizoma-Poria-Nelumbinis Semen 4∶4∶2∶1∶1） and the optimal prescription screened by uniform design. On this basis， the optimal prescription composition for maximizing the effect on ovarian reserve function was determined and preliminary insights into the underlying mechanisms of this prescription were gained. ResultsA total of 147 common targets were obtained from 278 targets of Tusizi prescription and 1 721 targets of DOR. GO analysis revealed 194 biological processes， primarily involving cellular responses to exogenous compound stimuli， negative regulation of apoptotic process， and positive regulation of cell proliferation. It identified 84 cellular components， including cell membrane， mitochondria， and neuronal cell body， as well as 144 molecular functions such as enzyme binding， estrogen response element binding， and nuclear estrogen receptor binding. The multivariate regression analysis revealed that when Tusizi prescription was composed of Cuscutae Semen， Lycii Fructus， Dioscoreae Rhizoma， Poria， and Nelumbinis Semen in a ratio of 27∶30∶17∶12∶14， the water extract of Tusizi prescription had the best effect of enhancing the viability of KGN cells. CCK-8 results showed that compared with the normal group， the hyperoside group demonstrated increased viability of ovarian germline stem cells （P<0.01）. The CCK-8， EdU， and ELISA results showed that compared with the normal group， the optimal prescription screened by uniform design and the water extract 11 of Tusizi prescription increased the proliferation and reduced the apoptosis of KGN cells （P<0.05， P<0.01）. ELISA results showed that compared with the normal group， the water extract 11 of Tusizi prescription promoted the E₂ secretion of KGN cells （P<0.05）， while the optimal prescription screened by uniform design had no significant effect on the E₂ secretion. ConclusionBoth the water extract 11 of Tusizi prescription （Cuscutae Semen-Lycii Fructus-Dioscoreae Rhizoma-Poria-Nelumbinis Semen 4∶4∶2∶1∶1） and the optimal prescription screened by uniform design （Cuscutae Semen-Lycii Fructus-Dioscoreae Rhizoma-Poria-Nelumbinis Semen 27∶30∶17∶12∶14） can improve the ovarian reserve function， and the former has better effect. Tusizi prescription can modulate biological processes （such as cell proliferation and apoptosis） and molecular functions （such as enzyme binding and estrogen response element binding） through active components like hyperoside to promote the proliferation and E₂ secretion and inhibit the apoptosis of KGN cells， thereby protecting the ovarian reserve function.

A 71-year-old male presented with esophageal cancer and severe aortic valve regurgitation. Treatment strategies for such patients are controversial. Considering the risks of cardiopulmonary bypass and potential esophageal cancer metastasis, we successfully performed transcatheter aortic valve implantation and minimally invasive three-incision thoracolaparoscopy combined with radical resection of esophageal cancer (McKeown) simultaneously in the elderly patient who did not require neoadjuvant treatment. This dual minimally invasive procedure took 6 hours and the patient recovered smoothly without any surgical complications.

Exercise-induced metabolic remodeling is a fundamental adaptive process whereby the body reorganizes systemic and cellular metabolism to meet the dynamic energy demands posed by physical activity. Emerging evidence reveals that such remodeling not only enhances energy homeostasis but also profoundly influences immune function through complex molecular interactions involving glucose, lipid, and protein metabolism. This review presents an in-depth synthesis of recent advances, elucidating how exercise modulates immune regulation via metabolic reprogramming, highlighting key molecular mechanisms, immune-metabolic signaling axes, and the authors’ academic perspective on the integrated “exercise-metabolism-immunity” network. In the domain of glucose metabolism, regular exercise improves insulin sensitivity and reduces hyperglycemia, thereby attenuating glucose toxicity-induced immune dysfunction. It suppresses the formation of advanced glycation end-products (AGEs) and interrupts the AGEs-RAGE-inflammation positive feedback loop in innate and adaptive immune cells. Importantly, exercise-induced lactate, traditionally viewed as a metabolic byproduct, is now recognized as an active immunomodulatory molecule. At high concentrations, lactate can suppress immune function through pH-mediated effects and GPR81 receptor activation. At physiological levels, it supports regulatory T cell survival, promotes macrophage M2 polarization, and modulates gene expression via histone lactylation. Additionally, key metabolic regulators such as AMPK and mTOR coordinate immune cell energy balance and phenotype; exercise activates the AMPK-mTOR axis to favor anti-inflammatory immune cell profiles. Simultaneously, hypoxia-inducible factor-1α (HIF-1α) is transiently activated during exercise, driving glycolytic reprogramming in T cells and macrophages, and shaping the immune landscape. In lipid metabolism, exercise alleviates adipose tissue inflammation by reducing fat mass and reshaping the immune microenvironment. It promotes the polarization of adipose tissue macrophages from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype. Moreover, exercise alters the secretion profile of adipokines—raising adiponectin levels while reducing leptin and resistin—thereby influencing systemic immune balance. At the circulatory level, exercise improves lipid profiles by lowering pro-inflammatory free fatty acids (particularly saturated fatty acids) and triglycerides, while enhancing high-density lipoprotein (HDL) function, which has immunoregulatory properties such as endotoxin neutralization and macrophage cholesterol efflux. Regarding protein metabolism, exercise triggers the expression of heat shock proteins (HSPs) that act as intracellular chaperones and extracellular immune signals. Exercise also promotes the secretion of myokines (e.g., IL-6, IL-15, irisin, FGF21) from skeletal muscle, which modulate immune responses, facilitate T cell and macrophage function, and support immunological memory. Furthermore, exercise reshapes amino acid metabolism, particularly of glutamine, arginine, and branched-chain amino acids (BCAAs), thereby influencing immune cell proliferation, biosynthesis, and signaling. Leucine-mTORC1 signaling plays a key role in T cell fate, while arginine metabolism governs macrophage polarization and T cell activation. In summary, this review underscores the complex, bidirectional relationship between exercise and immune function, orchestrated through metabolic remodeling. Future research should focus on causative links among specific metabolites, signaling pathways, and immune phenotypes, as well as explore the epigenetic consequences of exercise-induced metabolic shifts. This integrated perspective advances understanding of exercise as a non-pharmacological intervention for immune regulation and offers theoretical foundations for individualized exercise prescriptions in health and disease contexts.

ObjectiveTraditional Chinese medicine (TCM) constitutes a valuable cultural heritage and an important source of antitumor compounds. Poria (Poria cocos (Schw.) Wolf), the dried sclerotium of a polyporaceae fungus, was first documented in Shennong’s Classic of Materia Medica and has been used therapeutically and dietarily in China for millennia. Traditionally recognized for its diuretic, spleen-tonifying, and sedative properties, modern pharmacological studies confirm that Poria exhibits antioxidant, anti-inflammatory, antibacterial, and antitumor activities. Pachymic acid (PA; a triterpenoid with the chemical structure 3β-acetyloxy-16α-hydroxy-lanosta-8,24(31)-dien-21-oic acid), isolated from Poria, is a principal bioactive constituent. Emerging evidence indicates PA exerts antitumor effects through multiple mechanisms, though these remain incompletely characterized. Neuroblastoma (NB), a highly malignant pediatric extracranial solid tumor accounting for 15% of childhood cancer deaths, urgently requires safer therapeutics due to the limitations of current treatments. Although PA shows multi-mechanistic antitumor potential, its efficacy against NB remains uncharacterized. This study systematically investigated the potential molecular targets and mechanisms underlying the anti-NB effects of PA by integrating network pharmacology-based target prediction with experimental validation of multi-target interactions through molecular docking, dynamic simulations, and in vitro assays, aimed to establish a novel perspective on PA’s antitumor activity and explore its potential clinical implications for NB treatment by integrating computational predictions with biological assays. MethodsThis study employed network pharmacology to identify potential targets of PA in NB, followed by validation using molecular docking, molecular dynamics (MD) simulations, MM/PBSA free energy analysis, RT-qPCR and Western blot experiments. Network pharmacology analysis included target screening via TCMSP, GeneCards, DisGeNET, SwissTargetPrediction, SuperPred, and PharmMapper. Subsequently, potential targets were predicted by intersecting the results from these databases via Venn analysis. Following target prediction, topological analysis was performed to identify key targets using Cytoscape software. Molecular docking was conducted using AutoDock Vina, with the binding pocket defined based on crystal structures. MD simulations were performed for 100 ns using GROMACS, and RMSD, RMSF, SASA, and hydrogen bonding dynamics were analyzed. MM/PBSA calculations were carried out to estimate the binding free energy of each protein-ligand complex. In vitro validation included RT-qPCR and Western blot, with GAPDH used as an internal control. ResultsThe CCK-8 assay demonstrated a concentration-dependent inhibitory effect of PA on NB cell viability. GO analysis suggested that the anti-NB activity of PA might involve cellular response to chemical stress, vesicle lumen, and protein tyrosine kinase activity. KEGG pathway enrichment analysis suggested that the anti-NB activity of PA might involve the PI3K/AKT, MAPK, and Ras signaling pathways. Molecular docking and MD simulations revealed stable binding interactions between PA and the core target proteins AKT1, EGFR, SRC, and HSP90AA1. RT-qPCR and Western blot analyses further confirmed that PA treatment significantly decreased the mRNA and protein expression of AKT1, EGFR, and SRC while increasing the HSP90AA1 mRNA and protein levels. ConclusionIt was suggested that PA may exert its anti-NB effects by inhibiting AKT1, EGFR, and SRC expression, potentially modulating the PI3K/AKT signaling pathway. These findings provide crucial evidence supporting PA’s development as a therapeutic candidate for NB.

Aromatherapy refers to the method of using the aromatic components of plants in appropriate forms to act on the entire body or a specific area to prevent and treat diseases. Essential oils used in aromatherapy are hydrophobic liquids containing volatile aromatic molecules， such as limonene， linalool， linalool acetate， geraniol， and citronellol. These chemicals have been extensively studied and shown to have a variety of functions， including reducing anxiety， relieving depression， promoting sleep， and providing pain relief. Terpenoids are a class of organic molecules with relatively low lipid solubility. After being inhaled， they can pass through the nasal mucosa for transfer or penetrate the skin and enter the bloodstream upon local application. Some of these substances also have the ability to cross the blood-brain barrier， thereby exerting effects on the central nervous system. Currently， the academic community generally agrees that products such as essential oils and aromatherapy from aromatic plants have certain health benefits. However， the process of extracting a single component from it and successfully developing it into a drug still faces many challenges. Its safety and efficacy still need to be further verified through more rigorous and systematic experiments. This article systematically elaborated on the efficacy of aromatic substances， including plant extracts and natural small molecule compounds， in antibacterial and antiviral fields and the regulation of nervous system activity. As a result， a deeper understanding of aromatherapy was achieved. At the same time， the potential of these aromatic substances for drug development was thoroughly explored， providing important references and insights for possible future drug research and application.