Malignant gastrointestinal tumors （GT） mainly include laryngeal cancer， esophageal cancer， gastric cancer， pancreatic cancer， hepatocellular carcinoma， bile duct cancer， and colorectal cancer. At present， the morbidity and mortality of GT are high. Tumor immune escape is one of the key reasons for cancer development and treatment failure， and it is also the main direction of current tumor immunotherapy research. Traditional Chinese medicine （TCM） plays a role in treating GT and alleviating systemic symptoms， especially showing potential advantages in regulating the immune escape mechanism. This article elaborates on the immune escape mechanism of GT and systematically reviews that TCM active components or compound prescriptions act on key immune checkpoints such as programmed cell death protein-1 （PD-1） and programmed cell death ligand-1 （PD-L1） to reduce the proportion of marrow-derived suppressor cells （MDSCs）， promote the polarization of M1 macrophages， activate effector immune cells， enhance CD8⁺ T cell recruitment and interferon （IFN）-γ secretion， enhance the killing activity of natural killers （NKs）， and reduce foxhead box protein P3（FoxP3⁺）-positive regulatory T （Treg） cell infiltration. TCM active components or compound prescriptions can remodel the tumor microenvironment （TME）， such as improving immunosuppressive factors， promoting vascular normalization， and regulating intestinal microbiota. Through the regulation of TME， enhancement of antigen presentation， inhibition of immune checkpoint molecules， regulation of cellular network factors and metabolites， etc.， TCM active components or compound prescriptions enhance the immune function， thereby inhibiting the immune escape of GT. This paper summarizes and reflects on the research results of TCM in regulating immune escape to treat GT in recent years， aiming to help transform TCM from empirical medication to precision treatment based on immune regulation， reduce drug resistance and enhance treatment effect.

Objective: To investigate the effects of salvianolic acid B (Sal B) on the quality of stored red blood cells (RBC) and to preliminarily explore its underlying mechanisms. Methods: Whole blood was collected from healthy adult volunteers, and suspended RBC were prepared and stored in MAP (mannitol-adenine-phosphate) solution. The RBC suspensions were divided into a control group and a Sal B group, with the latter supplemented with Sal B at a final concentration of 10 μM. All samples were mixed and stored at 2-6℃. RBC were collected on days 0, 7, 14, 21, 28, and 35 for evaluation. RBC damage was assessed through cell counting, morphological observation, osmotic fragility test, and hemolysis rate measurement. Cytosolic ROS levels and intracellular SOD activity were measured to evaluate oxidative stress. Results: Sal B helped maintain RBC morphology and osmotic stability, and reduced the generation of morphologically abnormal cells such as spherocytes and echinocytes. On days 28 and 35, the hemolysis rate in the Sal B group was significantly lower than that in the control group. Compared with the control group, the Sal B group exhibited decreased cytosolic ROS levels and increased intracellular SOD activity from day 14 onward. Conclusion: Sal B alleviates RBC storage lesion by reducing oxidative stress.

ObjectiveBased on transcriptomics， to explore the mechanism of Hei Xiaoyaosan regulating the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway to improve the learning and memory ability of insomnia rats with liver depression syndrome. MethodsSixty 8-week-old male SD rats were randomly divided into the blank group， model group， eszopiclone group （0.09 mg·kg^-1）， and low， medium， and high dose groups of Hei Xiaoyaosan （3.82， 7.65， 15.30 g·kg^-1）， with ten rats in each group. Except for the blank group， the other groups were induced insomnia rat model with liver depression by chronic restraint， tail clamping stimulation and intraperitoneal injection of p-chlorophenylalanine （PCPA）. Each treatment group received intragastric administration according to the specified dosage， once a day for 14 consecutive days. The pentobarbital sodium cooperative sleep test， open field test， and Morris water maze test were used to test the sleep quality， depressive-like behavior， and learning and memory abilities of rats. Additionally， enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of 5-hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， brain-derived neurotrophic factor （BDNF）， glial cell line-derived neurotrophic factor （GDNF） and nitric oxide （NO） in hippocampus. Hematoxylin-eosin （HE） staining was performed to observe pathological changes of the hippocampal tissue， while terminal deoxynucleotidyl transferase deoxyuridine triphosphate （dUTP） nick end labeling （TUNEL） was used to evaluate apoptosis of hippocampal neurons. Transcriptomic sequencing technology was employed to identify differentially expressed genes in hippocampus between the model group and the blank group， as well as between the medium-dose group of Hei Xiaoyaosan and the model group. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis were performed on the intersecting genes. Subsequently， the enriched key genes and signaling pathways were analyzed and verified. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was utilized to assess the mRNA expression levels of phosphatase and tensin homolog （PTEN）， B-cell lymphoma-2 （Bcl-2）-like protein 11 （BCL2L11）， and mitogen-activated protein kinase 1 （MAPK1） in hippocampus， and Western blot was employed to evaluate the protein expressions of PI3K， phosphorylation （p）-PI3K， Akt， p-Akt， Bcl-2， Bcl-2-associated X protein （Bax）， and cleaved Caspase-3 in the same tissue. ResultsCompared with the blank group， the model group exhibited a reduction in body weight， an increase in sleep latency， and a decrease in sleep duration （P<0.01）. Additionally， rats showed obvious depression-like behavior， and their learning and memory abilities decreased. Furthermore， the contents of 5-HT， GABA， NO， BDNF and GDNF in hippocampus decreased （P<0.01）. Histological examination revealed a disorganized cell arrangement in the CA1 region of the hippocampus， characterized by irregular cell shapes， a reduced cell count， deeply stained and pyknotic nuclei， increased vacuolar degeneration， and an elevated apoptosis rate （P<0.01）. Compared with the model group， the body weight of the high and medium dose groups of Hei Xiaoyaosan increased， the sleep latency shortened and the sleep time prolonged （P<0.05， P<0.01）. Additionally， depression-like behavior and learning and memory abilities of rats were significantly improved， the levels of 5-HT， GABA， NO， BDNF and GDNF in the hippocampus increased （P<0.05， P<0.01）. These interventions also ameliorated pathological damage in the hippocampal CA1 area and reduced the apoptosis of hippocampal neurons （P<0.01）. Transcriptomic sequencing results indicated that Hei Xiaoyaosan might exert a therapeutic effect by regulating PI3K/Akt pathway through key mRNAs such as PTEN， BCL2L11， and MAPK1. The roles of these key mRNAs and proteins within PI3K/Akt pathway were further validated. In comparison to the blank group， the expression levels of PTEN， BCL2L11 and MAPK1 mRNA in the hippocampus of rats in the model group were increased （P<0.01）， while the protein expression levels of p-PI3K， p-Akt and Bcl-2 were decreased （P<0.01）， and the protein expression levels of PTEN， Bax and cleaved Caspase-3 were increased （P<0.01）. Compared with the model group， the high-dose and medium-dose groups of Hei Xiaoyaosan could down-regulate the expressions of PTEN， BCL2L11 and MAPK1 mRNAs （P<0.01）， up-regulate the expressions of p-PI3K， p-Akt and Bcl-2 proteins （P<0.01）， and down-regulate the protein expressions of PTEN， Bax and cleaved Caspase-3 （P<0.05， P<0.01）. ConclusionHei Xiaoyaosan may regulate PI3K/Akt signaling pathway by down-regulating expressions of key genes such as PTEN， BCL2L11 and MAPK1， and thus improve the learning and memory abilities of insomnia rats with liver depression syndrome.

Objective: Exploring the effect and mechanism of Xinyang Tablet on reduction of ferroptosis in myocardial cells from mice with chronic heart failure. Methods: Sixty C57BL/6J mice were randomly assigned to the sham, model, Xinyang Tablet low-dose (0.34 g/kg), Xinyang Tablet medium-dose (0.68 g/kg), Xinyang Tablet high-dose (1.36 g/kg), and perindopril (0.607 mg/kg) groups using a random number table method (10 mice in each group). Except for the sham group, all other groups underwent aortic arch constriction surgery to construct a chronic heart failure model. On the third day after completion of the modeling, each treatment group was administered the corresponding medication by gavage, while the sham and model groups were administered equal volumes of water by gavage once a day for eight consecutive weeks. After treatment, cardiac ultrasound was used to detect the structure and function of the mouse heart. Hematoxylin and eosin staining was used to detect pathological changes in mouse heart tissue. Masson staining was used to detect the proportion of fibrotic area of mouse heart tissue. Realtime fluorescence PCR was used to detect the mRNA expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), collagen 3α (Col3α), and myosin heavy chain 7 (MYH7) in mouse myocardial tissue. Transmission electron microscope was used to detect the ultrastructure of myocardial cell mitochondria. Reactive oxygen species (ROS) staining was used to detect the mean fluorescence intensity of ROS in myocardial tissue. Micro-determination was used to detect superoxide dismutase (SOD) activity in myocardial tissue. An immunofluorescence assay was used to detect the mean fluorescence intensity of phosphorylated histone deacetylase 2 (p-HDAC2) in myocardial cell. Western blotting was used to detect the protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), p-HDAC2, nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), glutathione peroxidase 4 (GPX4), and cystine glutamate reverse transporter (xCT) in mouse myocardial tissue. Results: Compared to the sham group, the model group showed a decrease in left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), an increase in left ventricular end-systolic diameter(LVESD) and left ventricular end-diastolic diameter (LVEDD), an increase in the proportion of cardiac fibrosis area, an increase in relative expression levels of ANP, BNP, Col3α, and MYH7 mRNA, an increase in ROS mean fluorescence intensity, a decrease in SOD activity, an increase in mean fluorescence intensity of p-HDAC2, an increase in relative expression levels of p-HDAC2 and NOX1 proteins, and a decrease in relative expression levels of Nrf2, GPX4, and xCT proteins (P<0.05). Myocardial fibrosis lesions are obvious, with disordered mitochondrial arrangement, decreased volume and shrinkage, increased membrane density, and reduced mitochondrial cristae. Compared to the model group, the LVEF and LVFS of mice in each dose group of Xinyang Tablet and the perindopril group increased, LVESD and LVEDD decreased, the proportion of fibrotic area of heart tissue decreased, the relative expression levels of ANP, BNP, Col3α, MYH7 mRNA decreased, ROS mean fluorescence intensity decreased, SOD activity increased, mean fluorescence intensity of p-HDAC2 decreased, relative expression levels of p-HDAC2 and NOX1 proteins decreased, and relative expression levels of Nrf2 and xCT proteins increased (P<0.05). Myocardial fibrosis was reduced, the mitochondrial arrangement was more regular, the mitochondria enlarged, the membrane density was reduced, and mitochondrial cristae increased. Compared to the model group, the relative expression level of the GPX4 protein in myocardial tissue increased in the Xinyang Tablet medium-, high-dose, and the perindopril groups (P<0.05). Conclusion Xinyang Tablet can improve ferroptosis and ventricular remodeling in mice with chronic heart failure by regulating the HDAC2-mediated Nrf2 antioxidant pathway.

OBJECTIVE: To investigate the short-term effectiveness of transtibial pull-out technique combined with side-to-side suture technique in treatment of complete radial tear of lateral meniscus body. METHODS: Between May 2020 and August 2023, 15 patients with complete radial tear of lateral meniscus body were repaired by arthroscopic transtibial pull-out technique combined with side-to-side suture technique. There were 11 males and 4 females, with an average age of 25.2 years (range, 15-43 years). Twelve cases were acute injuries and 3 were chronic injuries. All patients had tenderness in the lateral compartment of the knee. No abnormal alignment was observed on the X-ray films of the knee. MRI showed the complete radial tear of lateral meniscus body without associated injuries such as anterior cruciate ligament or cartilage. Preoperative Lysholm score was 44.5±6.4, International Knee Documentation Committee (IKDC) subjective score was 40.2±8.4, Tegner score was 1.3±1.1, and visual analogue scale (VAS) score for pain was 5.1±1.1. The operation time, incision healing, and complications such as vascular/nerve injury were recorded. During follow-up, the range of motion of the knee and tenderness in the lateral compartment of the knee were observed. The knee function and pain were evaluated using Lysholm score, Tegner score, IKDC subjective score, and VAS score. X-ray films and MRI of the knee were reexamined to assess knee degeneration. RESULTS: The operation time was 60-145 minutes (mean, 89.6 minutes). All incisions healed by first intention, and no complication such as vascular/nerve injury occurred. All patients were followed up 17-56 months (mean, 38.4 months). All patients had no knee extension limitation and 3 cases had tenderness in the lateral compartment of the knee. At last follow-up, the Lysholm score, IKDC subjective score, Tegner score, and VAS score for pain were 85.3±7.8, 82.1±15.7, 4.7±1.2, and 1.5±1.0, respectively, which were superior to those before operation ( P<0.05). Imaging reexamination showed that the meniscus was reset at 1 day after operation, and there was no sign of knee degeneration at last follow-up. CONCLUSION Transtibial pull-out technique combined with side-to-side suture technique can effectively treat the complete radial tear of lateral meniscus body and obtain good short-term effectiveness.
Humans ; Male ; Female ; Adult ; Tibial Meniscus Injuries/surgery* ; Adolescent ; Young Adult ; Arthroscopy/methods* ; Treatment Outcome ; Suture Techniques ; Tibia/surgery* ; Menisci, Tibial/surgery* ; Magnetic Resonance Imaging

OBJECTIVE: To investigate the surgical method and short-term effectiveness of arthroscopy edge-to-edge #-shaped suture in the treatment of the complete radial tear of the lateral meniscus body. METHODS: The clinical data of 13 patients with complete radial tear of lateral meniscus body between May 2020 and August 2023 were retrospectively analyzed. There were 10 males and 3 females, aged 15-38 years (mean, 24.2 years). There were 11 cases of acute injury and 2 cases of chronic injury, with time from injury to admission ranging from 2 days to 5 months. All patients had tenderness in the lateral joint space, and 2 patients with chronic injury had positive McMurray's sign. All patients were treated with arthroscopic edge-to-edge #-shaped suture technique. The knee joint activity and tenderness in the lateral joint space were detected, and the healing of the incision and the occurrence of complications were observed. X-ray films and MRI of the knee joint were performed to evaluate joint degeneration and meniscus healing. Lysholm score, International Knee Documentation Committee (IKDC) subjective score, Tegner score, and visual analogue scale (VAS) score were used to evaluate the functional recovery before and after operation. RESULTS: The operation time ranged from 46 to 100 minutes (mean, 80.08 minutes). All the incisions healed by first intention, and no complication such as intraoperative vascular and nerve injury or postoperative infection occurred. All 13 patients were followed up 20-59 months (mean, 29.3 months). All patients had no limitation of knee extension and flexion. One patient with chronic injury continued to have tenderness in the lateral space of the knee joint, while the remaining patients had no tenderness, swelling, and locking in the lateral space. Immediate postoperative MRI of knee joint showed continuous recovery of the lateral meniscus. At last follow-up, no degenerative changes were observed in X-ray films of knee joint. Except for 1 patient with chronic injury, the MRI of the other patients showed the healing performance after lateral meniscus suture. Lysholm score, IKDC subjective score, Tegner score, and VAS score all significantly improved when compared with those before operation (P<0.05). CONCLUSION The edge-to-edge #-shaped suture technique can effectively repair the complete radial tear of the lateral meniscus body, and the short-term effectiveness is satisfactory.
Humans ; Male ; Female ; Adult ; Tibial Meniscus Injuries/surgery* ; Arthroscopy/methods* ; Retrospective Studies ; Adolescent ; Young Adult ; Suture Techniques ; Treatment Outcome ; Menisci, Tibial/surgery* ; Sutures ; Knee Joint/surgery* ; Magnetic Resonance Imaging

Objective To investigate how culture duration affects the expression of immune membrane proteins in human monocyte-derived dendritic cells (DCs) and their exosomes (DEXs). Methods Human monocytes were induced with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) to differentiate into DCs and were subsequently matured with tumor necrosis factor α(TNF-α). Exosomes were isolated by ultracentrifugation, and DEXs were identified by transmission electron microscopy and Amnis imaging flow cytometry, which were also used to quantify the expression of immune membrane proteins on DCs and DEXs. Results On the 10th day of culture, DCs displayed high surface expression of CD11c, CD80, CD86, major histocompatibility complex class I (MHC-I), and MHC-II. Expression peaked at day 18(CD11c: 78.66%±20.33%, CD80: 76.41%±10.02%, CD86: 96.43%±0.43%, MHC-I: 84.71%±2.96%, MHC-II: 80.01%±7.03%). After day 24, the overall expression showed a declining trend, with statistically significant differences observed for all markers except CD80 and MHC-II. By day 30, 80% of the DCs still expressed CD80, CD86, and MHC-II. The expression of immune membrane proteins on DEX surfaces also reached its peak on day 18, followed by an overall decline with prolonged culture time, with statistically significant differences observed for all markers except CD80. Correlation analysis revealed a significant positive relationship between the expression levels of immune membrane proteins on DC and DEX surfaces (CD11c: r=0.98; CD80: r=0.65; CD86: r=0.82; MHC-I: r=0.86; MHC-II: r=0.93). Conclusion Human monocyte-derived DCs in vitro express high expression of immune membrane proteins and maintain stable expression over a specific period. The exosomes secreted by these cells similarly demonstrate high surface expression of immune membrane proteins, with temporal trends aligned with those of the parent DCs.
Humans ; Dendritic Cells/immunology* ; Exosomes/immunology* ; Monocytes/metabolism* ; Cells, Cultured ; Time Factors ; B7-1 Antigen/metabolism* ; Membrane Proteins/immunology* ; Cell Culture Techniques/methods* ; B7-2 Antigen/metabolism* ; Cell Differentiation ; CD11c Antigen/metabolism* ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology*

OBJECTIVES: Hypoxia/reoxygenation (H/R) injury is a critical pathological process during liver transplantation. Kazinol B has known anti-inflammatory, anti-apoptotic, and metabolic regulatory properties, but its protective mechanism in H/R-induced liver injury remains unclear. This study aims to investigate the protective effects and underlying mechanisms of Kazinol B in H/R-induced hepatocyte injury. METHODS: An ischemia-reperfusion model was established in healthy adult male Sprague-Dawley rats, and an in vitro H/R model was created using cultured hepatocytes. Hepatocytes were treated with Kazinol B (0-100 μmol/L) to assess cytotoxicity and protective effects. Cell viability was evaluated using the cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) release assays. Expression of apoptosis-related proteins, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad), and cleaved caspase-3, was detected by Western blotting. Reactive oxygen species (ROS) levels were assessed via fluorescence probes, and inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured using enzyme-linked immunosorbent assay (ELISA). TdT-mediated nick end labeling (TUNEL) staining was performed to assess DNA damage and apoptosis. RESULTS: Kazinol B had no significant effect on hepatocyte viability at 0-50 μmol/L, but showed cytotoxicity at 100 μmol/L (P<0.05). At 0.1-20 μmol/L, Kazinol B significantly improved cell survival, reduced LDH release, decreased apoptosis, and attenuated DNA damage (all P<0.001). At 10 μmol/L, Kazinol B markedly down-regulated Bad and cleaved caspase-3 (both P<0.05), and up-regulated Bcl-2 (P<0.01). It also dose-dependently reduced ROS levels and inflammatory cytokines TNF-α and IL-1β (all P<0.01). Both in vitro and in vivo, Kazinol B inhibited activation of the c-Jun N-terminal kinase (JNK) pathway without affecting extracellular regulated protein kinase (ERK) signaling (P>0.05). TUNEL staining showed that the protective effect of Kazinol B against apoptosis was partially reversed by the JNK agonist anisomycin (P<0.01). CONCLUSIONS Kazinol B mitigates hepatocyte injury induced by H/R by inhibiting the JNK signaling pathway. Its protective effect is associated with suppression of oxidative stress and inflammation, indicating its potential as a hepatoprotective agent.
Animals ; Hepatocytes/pathology* ; Rats, Sprague-Dawley ; Male ; Rats ; Reperfusion Injury/prevention & control* ; Apoptosis/drug effects* ; Reactive Oxygen Species/metabolism* ; MAP Kinase Signaling System/drug effects* ; Cell Survival/drug effects* ; Cell Hypoxia ; Cells, Cultured

Recent studies have demonstrated that the malignant proliferation and continuous progression of lymphoma are highly dependent on enhanced lipid metabolism. Consequently, targeting lipid metabolism pathways have emerged as a promising direction for lymphoma treatment. This paper reviews the fatty acid metabolism, cholesterol metabolism, and phospholipid metabolism in lymphoma, thereby providing novel insights for its therapeutic strategies.

OBJECTIVE To analyze the distribution of the nasopharyngeal microbiota in children with refractory chronic sinusitis and adenoid hypertrophy using 16S rRNA next-generation high-throughput sequencing technology,and to compare the effects of adenoidectomy on the nasopharyngeal microbiota in such patients,with the aim of providing microbiological evidence for the clinical treatment of refractory chronic sinusitis with adenoid hypertrophy.METHODS Children diagnosed with chronic sinusitis with adenoid hypertrophy who visited Chengdu Women and Children's Central Hospital from January 2024 to March 2025 and whose symptoms were not controlled after drug treatment were selected.They were divided into a non-surgical group and a surgical group based on whether they underwent adenoidectomy.The VAS scores,Lund-Kennedy scores,and microbial community detection rates between the two groups were compared.RESULTS The final VAS scores and Lund-Kennedy scores for surgical group were both lower than those for non-surgical group,with statistically significant differences(tVAS score=3.491,P<0.001;tLund-Kennedy score=4.166,P<0.001).Comparisons of microbial α diversity analysis and β diversity at the phylum and genus levels between the two groups showed no statistically significant differences(tα diversity analysis=0.524,P=0.604;Rβ diversity at the phylum level=0.075,P=0.454;Rthe genus level=0.117,P=0.538).The dominant bacterial groups at the phylum level were the same in both groups,including Proteobacteria,Bacillales,Actinobacteria,Bacteroidetes,and Firmicutes,but the average relative abundance differed between the two groups.Species comparison analysis showed that at the phylum level,the abundance of Proteobacteria and Thermodesulfovibrio in surgical group was higher than that in non-surgical group;At the genus level,the abundance of the genus Moraxella was higher in non-surgical group than in surgical group,while the abundance of the genera Acidovorax,Stenotrophomonas,Delftia,Burkholderia,Caballeronia,Paraburkholderia,Lactobacillus,Devosia,norank_f_Muribaculaceae,Paracoccus,and Kocuria was lower in non-surgical group than in surgical group.CONCLUSION Children with refractory sinusitis and adenoid hypertrophy all have rich microbial communities in the nasopharynx.Adenoid surgery has no significant effect on the diversity of the nasopharyngeal microbial community.However,the composition of the microbial community has changed,and there are significant species differences,which may be related to the resolution of local obstruction after adenoidectomy and changes in the survival environment of the nasopharyngeal microbial community.