Nanozymes are a distinct category of nanomaterials that exhibit catalytic properties resembling those of enzymes such as peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Nanozymes derived from Chinese herbal medicines exhibit the catalytic functions of their enzyme mimics, while retaining the specific medicinal properties of the herb (termed "herbzymes"). These nanozymes can be categorized into three main groups based on their method of synthesis: herb carbon dot nanozymes, polyphenol-metal nanozymes, and herb extract nanozymes. The reported catalytic activities of herbzymes include POD, SOD, CAT, and GPx. This review presents an overview of the catalytic activities and potential applications of nanozymes, introduces the novel concept of herbzymes, provides a comprehensive review of their classification and synthesis, and discusses recent advances in their biomedical applications. Furthermore, we also discuss the significance of research into herbzymes, including the primary challenges faced and future development directions.
Nanostructures/chemistry* ; Humans ; Herbal Medicine/methods* ; Superoxide Dismutase/chemistry* ; Catalase/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Catalysis ; Glutathione Peroxidase/chemistry*

Sonodynamic therapy (SDT) can potentially induce immunogenic cell death in tumor cells, leading to the release of ATP, and facilitating the initiation of an immune response. Nevertheless, the enzymes CD39 and CD73 can swiftly convert ATP into immunosuppressive adenosine (ADO), resulting in an immunosuppressive tumor microenvironment (TME). This study introduced a nanomedicine (QD/POM1@NP@M) engineered to reprogram TME by modulating the CD39/CD73/ADO pathway. The nanomedicine encapsulated sonosensitizers silver sulfide quantum dots, and the CD39 inhibitor POM1, while also incorporating homologous tumor cell membranes to enhance targeting capabilities. This integrated approach, on the one hand, stimulates the release of ATP via SDT, thereby initiating the immune response. In addition, it reduced the accumulation of ADO by inhibiting CD39 activity, which ameliorated the immunosuppressive TME. Upon administration, the nanomedicine demonstrated substantial anti-tumor efficacy by facilitating the infiltration of anti-tumor immune cells, while reducing the immunosuppressive cells. This modulation effectively transformed the TME from an immunologically "cold" state to a "hot" state. Furthermore, combined with the checkpoint inhibitor α-PDL1, the nanomedicine augmented systemic anti-tumor immunity and promoted the establishment of long-term immune memory. This study provides an innovative strategy for combining non-invasive SDT and ATP-driven immunotherapy, offering new ideas for future cancer treatment.

Objective:To investigate the expression of Artemin (ARTN) in malignant peripheral nerve sheath tumor (MPNST), its effect on the malignant behavior of MPNST cells, and its signaling pathway.Methods:Fifty-one MPNST paraffin embedded tissues through surgical resection at Tianjin Medical University Cancer Hospital from January 1995 to November 2011 were collected, the expression of the ARTN protein was detected by immunohistochemistry, and the relationship between the ARTN protein expression and the clinical pathological characteristics and prognosis were analyzed. In human MPNST cell lines ST-8814 (NF-1) and STS26T(sporadic), ARTN overexpression and low expression cell lines were constructed by transfecting ARTN overexpression plasmids and ARTN small interfering RNA (siRNA), respectively. The expression of ARTN mRNA was detected by real time quantitative polymerase chain reaction (RT-qPCR), the expression of the ARTN protein and Phosphoinositide 3-kinase(PI3K)/Akt signaling pathway related proteins were detected by Western blot. CCK-8 assay was used to detect cell proliferation ability, and cell invasion assay was used to detect cell invasion ability. The pathway proteins that interacted with ARTN were searched in the STRING database, and the functional pathways were clarified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The PI3K/Akt pathway specific inhibitor LY294002 was used to block the PI3K/Akt pathway of ST-8814 and STS26T cells to observe the changes in cell proliferation and invasion.Results:Among the 51 MPNST tissue specimens, 22 cases showed a high expression of the ARTN protein and 29 cases showed a low expression of the protein. Higher expressions of the ARTN protein was associated with larger tumor diameters and disease progression (recurrence or metastasis) (both P＜0.05). The median disease-free survival (DFS) of patients with a low expression of the ARTN protein was 26.2 months, and the median overall survival (OS) was 66.9 months. The median DFS and median OS of patients with a high expression of the ARTN protein were 10.7 months and 53.8 months, respectively. The log rank test results showed that the progression free survival rate of patients with a high expression of the ARTN protein was worse than that of patients with a low expression ( P=0.027), but the difference in overall survival rate between the two groups was not statistically significant ( P=0.790), which was also confirmed by Cox regression analysis. The CCK-8 assay results showed that after 48 hours of transfection, the absorbance ( A) values of ST-8814 and STS26T cells in the ARTN overexpression group were 1.35±0.01 and 1.10±0.02, respectively, which were higher than those in the empty plasmid control group (1.05±0.01 and 0.78±0.01, both P＜0.01), while the A values of ST-8814 and STS26T cells in the ARTN siRNA group were 0.35±0.01 and 0.61±0.01, respectively, which were lower than those in the control siRNA group (0.74±0.01 and 1.10±0.04, both P＜0.01). The results of cell invasion assay showed that the number of transmembrane cells in ST-8814 and STS26T cells overexpressing ARTN was (29.67±2.08) and (31.67±2.08), respectively, which were higher than those in the empty plasmid control group [(20.00±1.00) and (24.33±1.15), both P＜0.01]. The number of transmembrane cells in ST-8814 and STS26T cells in the ARTN siRNA group were (14.00±2.00) and (19.33±1.53), respectively, which were lower than those in the control siRNA group [(19.33±2.52) and (23.33±0.58), both P＜0.05].The KEGG results showed that ARTN is associated with multiple tumor signaling pathways, especially the PI3K/Akt signaling pathway. Western blot results showed that overexpression of ARTN upregulated the expression of p-PI3K and p-Akt proteins in ST-8814 and STS26T cells (both P＜0.01).After knocking down ARTN expression, the expression of p-PI3K and p-Akt proteins was significantly down regulated (both P＜0.01). LY294002 could significantly inhibit the effect of ARTN overexpression on ST-8814 and STS26T cells after blocking the PI3K/Akt pathway. The A values of ST-8814 and STS26T cells in the ARTN overexpression+LY294002 group were 1.09±0.06 and 0.82±0.01, respectively, which were lower than those in the ARTN overexpression group (1.50±0.01 and 1.29±0.01, respectively, both P＜0.01). The numbers of transmembrane cells in the cell invasion assay were 16.67±3.21 and 19.67±2.31, respectively, which were also lower than those in the ARTN overexpression group (29.67±2.08 and 31.67±2.08, respectively, both P＜0.01). Conclusions:In MPNST, a high expression of the ARTN protein was associated with larger tumor size, disease progression, and worse DFS. ARTN promotes the proliferation and invasion of MPNST cells through the PI3K/Akt signaling pathway.

OBJECTIVE To study regularity of different components whose skin permeability is enhanced by essential oils(EOs)from traditional Chinese medicine(TCM)with hot property.METHODS Five EOs from TCM with hot property,namely Galangal oil,Dried Ginger oil,Cinnamon oil,Pepper oil,and Evodia oil were prepared and used in further studies.The in vitro skin cytotoxici-ty of these EOs and chemical penetration enhancer(PE)Azone were compared.HPLC method was established to determine 9 TCM components that are usually used in permeation studies.And the in vitro permeation experiments were carried out using the modified Franz diffusion cell method to evaluate the penetration enhancement effects of five EOs.RESULTS The cytotoxicity test revealed the IC50 value of EOs was 3.63-8.15 times of that of Azone,the classical chemical PE.HPLC method showed perfect specificity and 9 TCM components performed well in linear relationship,precision,repeatability,stability,and average recovery rate.The results of multiple linear regression showed a significant association between the penetration enhancement effects of EOs from TCM with hot prop-erty and log P values of the TCM components.EOs from TCM with hot property showed satisfactory penetration enhancement effects for hydrophobic components with log P values in the range of 2.6-3.5,e.g.resveratrol,tetrahydropalmatine and quercetin.CONCLU-SION EOs from TCM with hot property should be reasonably selected as PE according to the oil-water partition coefficient of the in-gredients.

Background Accurate T-staging is critical for esophageal cancer therapy,but CT-based assessment has significant limitations.Large vision models(LVMs)hold promise,yet their zero-shot clinical diagnostic capability without fine-tuning remains unvalidated.Methods A retrospective analysis was conducted on the chest CT images from 98 esophageal cancer patients and 50 normal controls.Using radiologist-consensus as the gold standard,the zero-shot T-staging performance of 3 LVMs(GPT-5,Gemini,and MedGemma)was evaluated with prompts of varying complexity.Results GPT-5 exhibited the highest accuracy and stability.Significant biases were observed among models:Gemini tended to over-stage,while MedGemma showed a tendency to under-stage.All models faced challenges in identifying early-stage tumors,but structured prompts improved diagnostic performance for mid-to-late stage lesions.Conclusion LVMs have potential for zero-shot T-staging,but their performance highly depends on model choice and prompt design.The generic model GPT-5 show superior zero-shot generalization.However,current model performance is not yet clinically viable,especially for early diagnosis.Future work should focus on fine-tuning with high-quality clinical data and developing standardized prompt frameworks.

Background Accurate T-staging is critical for esophageal cancer therapy,but CT-based assessment has significant limitations.Large vision models(LVMs)hold promise,yet their zero-shot clinical diagnostic capability without fine-tuning remains unvalidated.Methods A retrospective analysis was conducted on the chest CT images from 98 esophageal cancer patients and 50 normal controls.Using radiologist-consensus as the gold standard,the zero-shot T-staging performance of 3 LVMs(GPT-5,Gemini,and MedGemma)was evaluated with prompts of varying complexity.Results GPT-5 exhibited the highest accuracy and stability.Significant biases were observed among models:Gemini tended to over-stage,while MedGemma showed a tendency to under-stage.All models faced challenges in identifying early-stage tumors,but structured prompts improved diagnostic performance for mid-to-late stage lesions.Conclusion LVMs have potential for zero-shot T-staging,but their performance highly depends on model choice and prompt design.The generic model GPT-5 show superior zero-shot generalization.However,current model performance is not yet clinically viable,especially for early diagnosis.Future work should focus on fine-tuning with high-quality clinical data and developing standardized prompt frameworks.

OBJECTIVE To study regularity of different components whose skin permeability is enhanced by essential oils(EOs)from traditional Chinese medicine(TCM)with hot property.METHODS Five EOs from TCM with hot property,namely Galangal oil,Dried Ginger oil,Cinnamon oil,Pepper oil,and Evodia oil were prepared and used in further studies.The in vitro skin cytotoxici-ty of these EOs and chemical penetration enhancer(PE)Azone were compared.HPLC method was established to determine 9 TCM components that are usually used in permeation studies.And the in vitro permeation experiments were carried out using the modified Franz diffusion cell method to evaluate the penetration enhancement effects of five EOs.RESULTS The cytotoxicity test revealed the IC50 value of EOs was 3.63-8.15 times of that of Azone,the classical chemical PE.HPLC method showed perfect specificity and 9 TCM components performed well in linear relationship,precision,repeatability,stability,and average recovery rate.The results of multiple linear regression showed a significant association between the penetration enhancement effects of EOs from TCM with hot prop-erty and log P values of the TCM components.EOs from TCM with hot property showed satisfactory penetration enhancement effects for hydrophobic components with log P values in the range of 2.6-3.5,e.g.resveratrol,tetrahydropalmatine and quercetin.CONCLU-SION EOs from TCM with hot property should be reasonably selected as PE according to the oil-water partition coefficient of the in-gredients.

Objective:To investigate the expression of Artemin (ARTN) in malignant peripheral nerve sheath tumor (MPNST), its effect on the malignant behavior of MPNST cells, and its signaling pathway.Methods:Fifty-one MPNST paraffin embedded tissues through surgical resection at Tianjin Medical University Cancer Hospital from January 1995 to November 2011 were collected, the expression of the ARTN protein was detected by immunohistochemistry, and the relationship between the ARTN protein expression and the clinical pathological characteristics and prognosis were analyzed. In human MPNST cell lines ST-8814 (NF-1) and STS26T(sporadic), ARTN overexpression and low expression cell lines were constructed by transfecting ARTN overexpression plasmids and ARTN small interfering RNA (siRNA), respectively. The expression of ARTN mRNA was detected by real time quantitative polymerase chain reaction (RT-qPCR), the expression of the ARTN protein and Phosphoinositide 3-kinase(PI3K)/Akt signaling pathway related proteins were detected by Western blot. CCK-8 assay was used to detect cell proliferation ability, and cell invasion assay was used to detect cell invasion ability. The pathway proteins that interacted with ARTN were searched in the STRING database, and the functional pathways were clarified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The PI3K/Akt pathway specific inhibitor LY294002 was used to block the PI3K/Akt pathway of ST-8814 and STS26T cells to observe the changes in cell proliferation and invasion.Results:Among the 51 MPNST tissue specimens, 22 cases showed a high expression of the ARTN protein and 29 cases showed a low expression of the protein. Higher expressions of the ARTN protein was associated with larger tumor diameters and disease progression (recurrence or metastasis) (both P＜0.05). The median disease-free survival (DFS) of patients with a low expression of the ARTN protein was 26.2 months, and the median overall survival (OS) was 66.9 months. The median DFS and median OS of patients with a high expression of the ARTN protein were 10.7 months and 53.8 months, respectively. The log rank test results showed that the progression free survival rate of patients with a high expression of the ARTN protein was worse than that of patients with a low expression ( P=0.027), but the difference in overall survival rate between the two groups was not statistically significant ( P=0.790), which was also confirmed by Cox regression analysis. The CCK-8 assay results showed that after 48 hours of transfection, the absorbance ( A) values of ST-8814 and STS26T cells in the ARTN overexpression group were 1.35±0.01 and 1.10±0.02, respectively, which were higher than those in the empty plasmid control group (1.05±0.01 and 0.78±0.01, both P＜0.01), while the A values of ST-8814 and STS26T cells in the ARTN siRNA group were 0.35±0.01 and 0.61±0.01, respectively, which were lower than those in the control siRNA group (0.74±0.01 and 1.10±0.04, both P＜0.01). The results of cell invasion assay showed that the number of transmembrane cells in ST-8814 and STS26T cells overexpressing ARTN was (29.67±2.08) and (31.67±2.08), respectively, which were higher than those in the empty plasmid control group [(20.00±1.00) and (24.33±1.15), both P＜0.01]. The number of transmembrane cells in ST-8814 and STS26T cells in the ARTN siRNA group were (14.00±2.00) and (19.33±1.53), respectively, which were lower than those in the control siRNA group [(19.33±2.52) and (23.33±0.58), both P＜0.05].The KEGG results showed that ARTN is associated with multiple tumor signaling pathways, especially the PI3K/Akt signaling pathway. Western blot results showed that overexpression of ARTN upregulated the expression of p-PI3K and p-Akt proteins in ST-8814 and STS26T cells (both P＜0.01).After knocking down ARTN expression, the expression of p-PI3K and p-Akt proteins was significantly down regulated (both P＜0.01). LY294002 could significantly inhibit the effect of ARTN overexpression on ST-8814 and STS26T cells after blocking the PI3K/Akt pathway. The A values of ST-8814 and STS26T cells in the ARTN overexpression+LY294002 group were 1.09±0.06 and 0.82±0.01, respectively, which were lower than those in the ARTN overexpression group (1.50±0.01 and 1.29±0.01, respectively, both P＜0.01). The numbers of transmembrane cells in the cell invasion assay were 16.67±3.21 and 19.67±2.31, respectively, which were also lower than those in the ARTN overexpression group (29.67±2.08 and 31.67±2.08, respectively, both P＜0.01). Conclusions:In MPNST, a high expression of the ARTN protein was associated with larger tumor size, disease progression, and worse DFS. ARTN promotes the proliferation and invasion of MPNST cells through the PI3K/Akt signaling pathway.

Objective:The treatment of head and neck in plexiform neurofibroma (PNF) is a major clinical problem, lacking consensus on surgical treatment, classification, operation timing, and treatment method. The purpose of this study was to provide a basis for further consensus formation by analyzing the clinical manifestations, surgical conditions, tumor recurrence, post-operation satisfaction, and changes in quality of life of patients undergoing PNF surgery in head and neck.Methods:Through medical record review and telephone follow-up, a retrospective analysis was conducted on neurofibromatosis type 1 (NF1) patients admitted for surgical treatment for PNF patient in head and neck from May 2012 to July 2022 in Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine. Complete collection and statistical analysis of patients’clinical data, using telephone follow-up to investigate the immediate postoperative satisfaction and long-term surgical satisfaction of patients and/or their families, as well as standardized quality of life questionnaires HRQol(health related quality of life) and PlexiQol(plexiform neurofibroma quality of life). Based on the data about changes in quality of life before and after surgery and long-term surgical satisfaction, patients were divided into surgical benefit and non-benefit groups. Binary and multivariate logistic regression analysis were used to analyze the clinical characteristics of patients with long-term surgical benefit.Results:Totally 512 patients with head and neck NF1 were admitted for surgery with complete medical records. 121 patients were identified as NF1 related PNF diagnosed by medical history and radiological examination, and effective follow-up was obtained. There were 70 males and 51 females, aged (25.60±12.85) years old, ranging from 7 to 63 years old, with 41 patients who were ≤ 18 years old and 80 patients over 18 years old. 62.81%(76/121) of patients exhibiting clinical dysfunctions, and the tumor mass were mainly characterized by invasive growth. 41.32%(50/121) of patients underwent multiple surgical treatments, with a total of 215 surgeries performed on 121 patients. The surgical objective included appearance improvement and functional repair. The incidence of postoperative complications was 6.05%(13/215). The follow-up period after last operation was (51.41±27.66) months, and 42.15%(51/121) of patients reported postoperative tumor recurrence. 76.03%(92/121) of patients were satisfied with immediate postoperative result, while the rate decreased to 46.28%(56/121) during long-term follow-up. Family members of patients who were ≤ 18 years old had a higher proportion of dissatisfaction with the scars caused by surgery and a stronger willingness to undergo another surgery. The tumor recurrence was closely related to surgical benefits ( OR=2.32, P<0.05). Further analysis found that the gender and age of patients were the main risk factors for the recurrence. The recurrence risk in patients ≤ 18 years old was significantly higher than in that over 18 years old( OR=3.49, P=0.004), and the highest in the 7-12 year-old group, reaching 68.42%(13/19). The recurrence risk in male patients was significantly lower than that in females ( OR=0.40, P=0.026). Conclusion:The clinical manifestations of PNF patients in head and neck region are complex. Clinical diagnosis and treatment in PNF should focus on the applications in comprehensive method such as full preoperative evaluation, active multi-disciplinary treatment cooperation and combined therapies in order to improve the safety and effectiveness of treatment and reduce tumor recurrence.