Objective To investigate the efficacy and safety of Xihuang capsules as an adjuvant treatment for metastatic colorectal cancer and their impact on immune function. Methods A retrospective analysis was conducted on clinical data from 112 patients diagnosed with metastatic colorectal cancer. The patients were categorized into two groups: a control group (n=56) that did not take Xihuang capsules and an observation group (n=56) that did. The efficacy, improvement of quality of life, toxic and side effects and immune function of the two groups were analyzed and compared. Results After treatment, the disease control rate (DCR) and the rate of improvement in quality of life were significantly higher in the observation group compared to the control group. Additionally, levels of carcinoembryonic antigen (CEA) and the incidence of adverse reactions, including bone marrow suppression and liver and kidney function damage, were significantly lower in the observation group. Furthermore, the percentages of CD4⁺ and CD8⁺ T cells, the CD8⁺/CD4⁺ T cells ratio, as well as serum levels of high mobility group box-1 (HMGB1) and interleukin 2 (IL-2) in observation group were significantly elevated compared to pre-treatment levels. Subgroup analysis revealed that patients with a Karnofsky Performance Status (KPS) score ≤80, a high CD8⁺/CD4⁺ T cells ratio, and elevated HMGB1 levels experienced a significantly higher objective response rate (ORR) in the observation group. Conversely, patients with stage IVB disease, who had KPS score ≤80, a low CD8⁺/CD4⁺ T cells ratio and high CEA and IL-2 levels demonstrated a more pronounced DCR in the observation group. Conclusion Xihuang capsules exhibit promising clinical efficacy as an adjuvant treatment for advanced colorectal cancer. They not only enhance patients' quality of life and reduce the toxic and adverse effects of chemotherapy, but also improve immune function. These benefits are particularly significant in patients with a high tumor burden, indicating that Xihuang capsules are worthy of clinical application.
Humans ; Colorectal Neoplasms/immunology* ; Male ; Female ; Middle Aged ; Drugs, Chinese Herbal/adverse effects* ; Capsules ; Aged ; Carcinoembryonic Antigen/blood* ; Retrospective Studies ; Quality of Life ; Adult ; Neoplasm Metastasis ; Interleukin-2/blood* ; HMGB1 Protein/blood* ; Chemotherapy, Adjuvant

OBJECTIVES: To study the protective effect of melatonin (Mel) against oxygen-induced retinopathy (OIR) in neonatal mice and the role of the HMGB1/NF-κB/NLRP3 axis. METHODS: Neonatal C57BL/6J mice, aged 7 days, were randomly divided into a control group, a model group (OIR group), and a Mel treatment group (OIR+Mel group), with 9 mice in each group. The hyperoxia induction method was used to establish a model of OIR. Hematoxylin and eosin staining and retinal flat-mount preparation were used to observe retinal structure and neovascularization. Immunofluorescent staining was used to measure the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis and lymphocyte antigen 6G. Colorimetry was used to measure the activity of myeloperoxidase. RESULTS: The OIR group had destruction of retinal structure with a large perfusion-free area and neovascularization, while the OIR+Mel group had improvement in destruction of retinal structure with reductions in neovascularization and perfusion-free area. Compared with the control group, the OIR group had significant increases in the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis, the expression of lymphocyte antigen 6G, and the activity of myeloperoxidase (P<0.05). Compared with the OIR group, the OIR+Mel group had significant reductions in the above indices (P<0.05). Compared with the control group, the OIR group had significant reductions in the expression of melatonin receptors in the retina (P<0.05). Compared with the OIR group, the OIR+Mel group had significant increases in the expression of melatonin receptors (P<0.05). CONCLUSIONS Mel can alleviate OIR-induced retinal damage in neonatal mice by inhibiting the HMGB1/NF-κB/NLRP3 axis and may exert an effect through the melatonin receptor pathway.
Animals ; Mice ; HMGB1 Protein ; Melatonin/therapeutic use* ; Mice, Inbred C57BL ; NF-kappa B ; NLR Family, Pyrin Domain-Containing 3 Protein ; Oxygen/adverse effects* ; Peroxidase ; Receptors, Melatonin ; Retinal Diseases/drug therapy*

PURPOSE: Appropriate animal models of atherosclerotic plaque are crucial to investigating the pathophysiology of atherosclerosis, as well as for the evaluation of the efficacy and safety of vascular devices. We aimed to develop a novel animal model that would be suitable for the study of advanced atherosclerotic lesions in vivo. MATERIALS AND METHODS: Atherosclerotic plaque was induced in 24 iliac arteries from 12 rabbits by combining a high cholesterol diet, endothelial denudation, and injection into the vessel wall with either saline (n=5), olive oil (n=6), or inflammatory proteins [n=13, high-mobility group protein B1 (HMGB1) n=8 and tumor necrosis factor (TNF)-α n=5] using a Cricket™ Micro-infusion catheter. Optical coherence tomography (OCT) was performed to detect plaque characteristics after 4 weeks, and all tissues were harvested for histological evaluation. RESULTS: Advanced plaque was more frequently observed in the group injected with inflammatory proteins. Macrophage infiltration was present to a higher degree in the HMGB1 and TNF-α groups, compared to the oil or saline group (82.1±5.1% and 94.6±2.2% compared to 49.6±14.0% and 46.5±9.6%, p-value<0.001), using RAM11 antibody staining. On OCT, lipid rich plaques were more frequently detected in the inflammatory protein group [saline group: 2/5 (40%), oil group: 3/5 (50%), HMGB1 group: 6/8 (75%), and TNF-α group: 5/5 (100%)]. CONCLUSION: These data indicate that this rabbit model of atherosclerotic lesion formation via direct injection of pro-inflammatory proteins into the vessel wall is useful for in vivo studies investigating atherosclerosis.
Animals ; Cholesterol, Dietary/administration & dosage ; *Disease Models, Animal ; Endothelium/surgery ; HMGB1 Protein/*adverse effects ; Iliac Artery/diagnostic imaging/pathology/surgery ; Injections, Intra-Arterial ; Macrophages ; Male ; Olive Oil/adverse effects ; Plaque, Atherosclerotic/*chemically induced/diagnostic imaging/pathology ; Rabbits ; Sodium Chloride/adverse effects ; Tomography, Optical Coherence ; Tumor Necrosis Factor-alpha/*adverse effects

The purpose of the present study is to explore the protective effects of sodium butyrate (SB) pretreatment on concanavalin A (Con A)-induced acute liver injury in mice. The model animals were first administered intraperitoneally with SB. Half an hour later, acute liver injury mouse model was established by caudal vein injection with Con A (15 mg/kg). Then, levels of serous alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using standard clinical method by an automated chemistry analyzer, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured by ELISA, and pathological changes in hepatic tissue were observed by using HE staining and light microscopy. The expression and release of high-mobility group box 1 (HMGB1) were assessed by using reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and ELISA. The results showed that the pretreatment of SB significantly protected Con A-treated mice from liver injury as evidenced by the decrease of serum ALT, AST (P < 0.01) and reduction of hepatic tissues necrosis. SB also decreased levels of serous TNF-α and IFN-γ (P < 0.01). Furthermore, the expression and release of HMGB1 were markedly inhibited by SB pretreatment (P < 0.05 or P < 0.01). These results suggest that the attenuating effect of SB on Con A-induced acute liver injury may be due to its role of reducing the TNF-α and IFN-γ production, and inhibiting HMGB1 expression and release.
Alanine Transaminase ; metabolism ; Animals ; Aspartate Aminotransferases ; metabolism ; Butyric Acid ; pharmacology ; Chemical and Drug Induced Liver Injury ; drug therapy ; Concanavalin A ; adverse effects ; Disease Models, Animal ; HMGB1 Protein ; metabolism ; Interferon-gamma ; metabolism ; Liver ; pathology ; Mice ; Tumor Necrosis Factor-alpha ; metabolism