Traditional Chinese medicine(TCM) capable of clearing heat and removing toxin is most commonly used in clinical practice and has the effect of removing fire-heat and toxin. Studies have shown that most of the Ilex plants have the effect of clearing heat and removing toxin, among which the varieties of I. cornuta, I. pubescens, I. rotunda, I. latifolia, and I. chinensis are most widely used. These plants generally contain triterpenoids and their glycosides, alkaloids, flavonoids, phenylpropanoids, and other chemical components, especially pentacyclic triterpenoids. According to their skeletons, pentacyclic triterpenoids can be divided into the oleanane type, the ursane type, the lupinane type, etc. Among them, ursane-type components are the most abundant, and 136 species have been found so far. These components have been proved to have pharmacological effects such as anti-inflammatory, anti-tumor, hypolipidemic, anti-thrombosis, cardiomyocyte-protective, antibacterial, and hepatoprotective effects. Therefore, this paper systematically reviews the domestic and foreign literature on Ilex plants with a focus on the research progress on pentacyclic triterpenoids and their pharmacological activities, aiming to provide reference for the development of TCM resources with the effect of clearing heat and removing toxin.
Ilex/chemistry* ; Plants, Medicinal/chemistry* ; Pentacyclic Triterpenes/pharmacology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Animals

OBJECTIVE: To explore the morphological characteristics of the postero-superior protuberance of the calcaneus and to explore its relationship with Haglund malformation. METHODS: Ankle lateral X-ray films of 391 hospitalized patients between May 2021 and June 2024 were retrospectively collected. The morphological parameters of the postero-superior protuberance of the calcaneus were measured, including the length of the base, the height of the base, and the tip angle of the postero-superior protuberance of the calcaneus, and the morphological types were classified according to the above parameters, including the peak type, the hill type, and the flat type. The related parameters of Haglund malformation were measured, including Fowler-Philipp angle (FPA), calcaneal pitch angle (CPA), parallel pitch line (PPL), Chauveaux-Liet angle (CLA), and X/Y ratio (total calcaneal length/length of greater tuberosity of calcaneus). The differences of the morphological parameters of the postero-superior protuberance of the calcaneus and the related indicators of Haglund deformity among the three types and between the males and the females were compared and analyzed, and the differences of the positive numbers of the related indicators of Haglund deformity among the three types were compared. RESULTS: According to the morphological parameters of the postero-superior protuberance of the calcaneus, there were 64 cases of peak type, 245 cases of hill type, and 82 cases of flat type. There was no significant difference in the length of the base of the postero-superior protuberance of the calcaneus, CPA, CLA, and X/Y ratio among the three types ( P>0.05). Among the three types, the peak type had the largest FPA and the flat type had the smallest ( P<0.05); the peak type had the smallest tip angle of the postero-superior protuberance of the calcaneus and the flat type had the largest ( P<0.05); the positive rate of PPL in the hill type was significantly higher than that in the peak type and flat type ( P<0.05); the height of the base of the postero-superior protuberance of the calcaneus in the flat type was the smallest ( P<0.05). FPA, CPA, CLA, PPL, and X/Y ratio were positive in 2, 42, 172, 142, and 77 patients, respectively. There was no significant difference in the number of positive Haglund deformity indicators among the three types ( P>0.05). There was no significant difference between male and female patients in the tip angle of the postero-superior protuberance of the calcaneus, FPA, the positive rate of PPL, and X/Y ratio ( P>0.05). The length and the height of the base of the postero-superior protuberance of the calcaneus, CPA, and CLA in male patients were significantly higher than those in female patients ( P<0.05). CONCLUSION The postero-superior protuberance of the calcaneus can be divided into three types: the peak type, the hill type, and the flat type. The peak type is more likely to suffer from Haglund deformity, and the males are more likely to suffer from Haglund deformity than the females.
Humans ; Calcaneus/anatomy & histology* ; Male ; Female ; Retrospective Studies ; Adult ; Middle Aged ; Adolescent ; Young Adult ; Radiography ; Child ; Aged

OBJECTIVES: Psoriasis is associated with lipid metabolism disorders, but the underlying mechanisms remain unclear. This study aims to investigate the role of trimethylamine N-oxide (TMAO) in lipid metabolism dysregulation in psoriasis. METHODS: An imiquimod (IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters, TMAO levels, and liver flavin monooxygenase 3 (FMO3) mRNA expression. Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles. To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model, exogenous TMAO, choline, or 3,3-dimethyl-1-butanol (DMB) were administered via intraperitoneal injections or diet in IMQ-treated mice. Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways. RESULTS: IMQ-induced psoriatic mice exhibited abnormal glucose, insulin, and lipid levels. IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2 (Glut2) and silence information regulator 1 (Sirt1), while upregulating glucose transporter 4 (Glut4) and peroxisome proliferator-activated receptor gamma (PPARγ). Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice. Additionally, liver FMO3 mRNA expression was increased in the psoriatic mouse model. In patients, TMAO levels positively correlated with Psoriasis Area and Severity Index (PASI) scores, serum triglyceride (TG), and total cholesterol (TC) levels. The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice. A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice, whereas DMB treatment alleviated these effects. RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122 (miR-122), which may suppress the expression of gremlin 2 (GREM2), thus contributing to lipid metabolism disorder. CONCLUSIONS TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.
Animals ; Methylamines/blood* ; Mice ; Psoriasis/chemically induced* ; Lipid Metabolism/drug effects* ; Humans ; Male ; Liver/metabolism* ; Female ; Oxygenases/genetics* ; Disease Models, Animal ; Lipid Metabolism Disorders/etiology* ; Adult ; Mice, Inbred C57BL

Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

Objective Focusing on gynecological surgery,we constructed a prediction model for surgical duration by extracting features from unstructured surgical planning texts and integrating multimodal data via artificial intelligence technology.Methods The clinical data of 34 614 patients who underwent gynecologic surgeries at West China Second University Hospital,Sichuan University between January 2022 and October 2024 were collected.An embedding-transformer model was constructed to convert surgical planning texts into a one-dimensional numerical feature,referred to as the step feature.The predictive value of the step feature was assessed by comparing the performance improvements of linear regression,random forest,eXtreme Gradient Boosting(XGBoost),support vector regression,K-nearest neighbor regression,and artificial neural network algorithms in two scenarios—with and without the step feature as an input.The out-of-sample prediction accuracy of the models was assessed using mean absolute error(MAE),root mean squared error(RMSE),and R-squared(R2).Furthermore,the model interpretability was examined using SHapley Additive exPlanations(SHAP)values.Results SHAP results showed that the step feature had the highest predictive contribution.Temporal factors in surgical scheduling also influenced gynecological surgery duration.The XGBoost model demonstrated optimal performance on the test set,significantly improving prediction accuracy with a 40.43%increase in R2,while reducing MAE and RMSE by 21.27%and 20.13%,respectively,compared to the baseline model without the step feature.Conclusion The embedding-transformer model developed in this study effectively extracts features from surgical planning texts and enhances the predictive performance of machine learning models.The XGBoost prediction model can assist hospital administrators in implementing more refined management of gynecological surgeries and improving the utilization efficiency of surgical resources.

Objective Based on the background of disease diagnosis related groups(DRGs)in public hospitals to construct the nursing quality evaluation index system for percutaneous radiofrequency ablation(PRFA)of liver cancer so as to improve the nursing quality for PRFA of liver cancer.Methods Using three-dimensional quality model and through interview,literature analysis,two rounds of Delphi expert letter inquiry and analytic hierarchy process,the evaluation standard of PRFA nursing quality of liver cancer was established,and its effect was validated in clinical practice.Results The evaluation index system of PRFA nursing quality for liver cancer was constructed,which included 3 first-level indexes,9 second-level indexes and 22 third-level indexes.After clinical application,the incidence of intraoperative and postoperative moderate-severe pain,the incidence of high fever,and the 24-hour number of times required care in the intervention group were lower than those in the control group(P＜0.05),the incidence of postoperative Ⅲ degree vomiting in the intervention group was remarkably lower than that in the control group(P＜0.01),and the average hospitalization days in the intervention group were less than those in the control group(P＜0.05),and the average hospitalization expense in the intervention group was lower than that in the control group,but the difference was not statistically significant(P＞0.05).Conclusion The PRFA nursing quality evaluation index system for liver cancer is scientific and practical,which is helpful for improving the outcome of patients and promoting the quality of nursing.

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Objective To express recombinant Burkholderia pseudomallei(B.pseudomallei)type Ⅲ secretion system BipD protein,prepare its polyclonal antibodies and verify their immunological traits.Methods The recombinant pET-28a-BipD plasmid was generated,and the pET-28a-BipD-carried E.coli BL21(DE3)bacteria were induced with isopropyl-β-d-thiogalactoside(IPTG)to express recombinant BipD(rBipD)protein.The rBipD was obtained by affinity chromatography using His Trap column,then mixed with Fredrick's adjuvant to immunize BALB/c mice by intraperitoneal injection in order to obtain anti-rBipD polyclonal antibodies.The immunoreactivity of rBipD was detected by Western blot assay using rabbit anti-melioidosis serum and the serum from melioidosis patients.The immunogenicity of rBipD was evaluated using Western blotting and immunofluorescence staining.Finally,rBipD was used to establish an indirect ELISA to detect serum antibodies of clinical melioidosis patients.Results The recombinant plasmid pET-28a-BipD was successfully constructed and transformed into E.coli BL21(DE3)to induce rBipD expression with IPTG treatment.The obtained rBipD had a relative molecular weight of 36×103 and a purity of 95.4％,and had good immunogenicity and immunoreactivity.It could induce the production of specific antibodies after immunizing mice,and mouse polyclonal antibodies against rBipD were prepared with the titer of 1∶512 000.rBipD of 5.0 μg/mL produced specific immune response with the serum of melioidosis patients,but had no specific reaction with the serum of tuberculosis patients,with statistical difference(P＜0.01).Conclusion rBipD with immunological activity is successfully prepared and purified,and its polyclonal antibodies are also developed,which provide a good tool for clinical immunological diagnosis and study of immune mechanism of B.pseudomallei infection.

Objective To analyze the mechanism that Hcp1 protein in type Ⅵ secretion system of Burkholderia pseudomallei(B.pseudomallei)mediates the formation of multinucleated giant cells(MNGCs)when host cells are infected by the bacterium.Methods The mutant strain(BPC006 Δhcp1)and complementation strain(BPC006 Δhcp1::hcp1)were constructed by homologous recombination and plasmid complement technology,respectively.After RAW264.7 cells were infected with B.pseudomallei,the localization of Hcp1 in host cells was analyzed by immunofluorescence staining.The localization was further verified by cytoplasmic-membrane isolation in 293T cells after transfecting pCDNA4.1-Hcp1.The biological significance and effect of Hcp1 were explored by the anti-Hcp1 polyclonal antibody blocking and the formation of MNGC was detected by Giemsa staining.Results Western blotting showed that BPC006 Δhcp1 could not express Hcp1,while BPC006 Δhcp1::hcp1 restored Hcp1 expression.The above results proved that the mutant and complement strains were successfully constructed.Both cellular immunofluorescence co-localization and cytoplasmic-membrane isolation experiments showed that Hcp1 localized to host cell membranes.Last but not least,compared with the control group,anti-Hcp1 polyclonal antibodies inhibited the formation of MNGC(P＜0.01).Conclusion Hcp1 protein in type Ⅵ secretion system of B.pseudomallei is able to translocate to the RAW264.7 cell membranes and plays an important role in the formation of MNGCs.