The generation of drug resistance in the process of tumor treatment is the key problem that the tumor cannot continue to be effectively treated. Studies have found that the drug resistance of multiple tumors is related to GSDME. Some chemotherapeutics can further induce programmed death of drug-resistant tumor cells through GSDME protein mediated by caspase-3, which is called pyrodeath. This paper reviews some clinical studies on the treatment of GSDME-related drug-resistant tumor cells, providing new insights and ideas for further treatment of clinical drug resistance.

Objective To investigate the effect and mechanism of action of epigallocatechin-3-gallate(EGCG)in the treatment of experimental metabolic dysfunction-associated steatohepatitis(MASH),and to provide a basis for clinical development and application.Methods A total of 32 experimental C57BL/6J mice were randomly divided into normal diet group(Con group with 8 mice)and model group with 24 mice.The mice in the model group were given a high-trans fatty acid high-carbohydrate(HFHC)diet for 24 weeks to establish a model of MASH,and at the end of week 24,the mice in the model group were further divided into HFHC group,EGCG treatment group(100 mg·kg-1·d-1),and obeticholic acid treatment group(10 mg·kg-1·d-1),with 8 mice in each group.After 6 weeks of treatment,samples were collected to observe the general conditions of mice;the content of triglycerides(TG)and hydroxyproline in liver tissue and the serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were measured;HE staining,oil red O staining,and picrosirius red staining were used to observe liver histopathological changes.In the in vitro experiment,L02 cells were induced with free fatty acid(FFA)to establish a model of lipid deposition,and the cells were divided into Con group,FFA group,and EGCG group.The content of TG in cells was measured,as well as the results of oil red O staining and the relative mRNA expression levels of TNF-α,CCL2,and CXCL10.The transcriptomics technique was used to identify differentially expressed genes between the Con group,the HFHC group,and the EGCG group and perform the GSEA analysis,and pathways with a P-adjust value of<0.05 that were associated with MASH were further classified into metabolism-related pathways and inflammation-related pathways.The specific signaling pathways in each category were ranked based on the degree of enrichment,and key genes in the top three pathways were verified by PCR in vivo.Key genes in the NOD-like receptor signaling pathway were verified by Western blotting.A one-way analysis of variance was used for comparison of normally distributed continuous data with homogeneity of variance between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the HFHC group,the EGCG group had significant reductions in the content of TG in liver tissue(P<0.05)and the serum levels of ALT and AST(P<0.05).Oil red O staining showed significant alleviation of hepatocyte fatty degeneration in the EGCG group,HE staining showed that EGCG effectively alleviated inflammation,and picrosirius red staining showed a significant reduction in the number of fibrous tissue after EGCG treatment.There was a significant reduction in the content of hydroxyproline in liver tissue after EGCG intervention(P<0.01).Cell experiments showed that compared with the FFA group,the EGCG group had a significant reduction in the content of TG,and oil red O staining showed the disappearance of lipid droplets in the EGCG group compared with the FFA group,with significant reductions in the relative mRNA expression levels of the inflammatory factors TNF-α,CCL2,and CXCL10(all P<0.01).The transcriptomics analysis identified 230 differentially expressed genes between the HFHC group and the EGCG group,among which there were 108 upregulated genes and 122 downregulated genes.EGCG significantly reduced the levels of the key proteins TLR4,NLRP3,and IL-1β in the NOD-like receptor signaling pathway in liver tissue(all P<0.05).Conclusion EGCG can significantly alleviate lipid deposition,inflammation,and fibrosis in the mouse model of MASH and improve lipid deposition and inflammatory injury in L02 cells,possibly by regulating the NOD-like receptor signaling pathway.

Objective To investigate the effect and mechanism of action of epigallocatechin-3-gallate(EGCG)in the treatment of experimental metabolic dysfunction-associated steatohepatitis(MASH),and to provide a basis for clinical development and application.Methods A total of 32 experimental C57BL/6J mice were randomly divided into normal diet group(Con group with 8 mice)and model group with 24 mice.The mice in the model group were given a high-trans fatty acid high-carbohydrate(HFHC)diet for 24 weeks to establish a model of MASH,and at the end of week 24,the mice in the model group were further divided into HFHC group,EGCG treatment group(100 mg·kg-1·d-1),and obeticholic acid treatment group(10 mg·kg-1·d-1),with 8 mice in each group.After 6 weeks of treatment,samples were collected to observe the general conditions of mice;the content of triglycerides(TG)and hydroxyproline in liver tissue and the serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were measured;HE staining,oil red O staining,and picrosirius red staining were used to observe liver histopathological changes.In the in vitro experiment,L02 cells were induced with free fatty acid(FFA)to establish a model of lipid deposition,and the cells were divided into Con group,FFA group,and EGCG group.The content of TG in cells was measured,as well as the results of oil red O staining and the relative mRNA expression levels of TNF-α,CCL2,and CXCL10.The transcriptomics technique was used to identify differentially expressed genes between the Con group,the HFHC group,and the EGCG group and perform the GSEA analysis,and pathways with a P-adjust value of<0.05 that were associated with MASH were further classified into metabolism-related pathways and inflammation-related pathways.The specific signaling pathways in each category were ranked based on the degree of enrichment,and key genes in the top three pathways were verified by PCR in vivo.Key genes in the NOD-like receptor signaling pathway were verified by Western blotting.A one-way analysis of variance was used for comparison of normally distributed continuous data with homogeneity of variance between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the HFHC group,the EGCG group had significant reductions in the content of TG in liver tissue(P<0.05)and the serum levels of ALT and AST(P<0.05).Oil red O staining showed significant alleviation of hepatocyte fatty degeneration in the EGCG group,HE staining showed that EGCG effectively alleviated inflammation,and picrosirius red staining showed a significant reduction in the number of fibrous tissue after EGCG treatment.There was a significant reduction in the content of hydroxyproline in liver tissue after EGCG intervention(P<0.01).Cell experiments showed that compared with the FFA group,the EGCG group had a significant reduction in the content of TG,and oil red O staining showed the disappearance of lipid droplets in the EGCG group compared with the FFA group,with significant reductions in the relative mRNA expression levels of the inflammatory factors TNF-α,CCL2,and CXCL10(all P<0.01).The transcriptomics analysis identified 230 differentially expressed genes between the HFHC group and the EGCG group,among which there were 108 upregulated genes and 122 downregulated genes.EGCG significantly reduced the levels of the key proteins TLR4,NLRP3,and IL-1β in the NOD-like receptor signaling pathway in liver tissue(all P<0.05).Conclusion EGCG can significantly alleviate lipid deposition,inflammation,and fibrosis in the mouse model of MASH and improve lipid deposition and inflammatory injury in L02 cells,possibly by regulating the NOD-like receptor signaling pathway.

The generation of drug resistance in the process of tumor treatment is the key problem that the tumor cannot continue to be effectively treated. Studies have found that the drug resistance of multiple tumors is related to GSDME. Some chemotherapeutics can further induce programmed death of drug-resistant tumor cells through GSDME protein mediated by caspase-3, which is called pyrodeath. This paper reviews some clinical studies on the treatment of GSDME-related drug-resistant tumor cells, providing new insights and ideas for further treatment of clinical drug resistance.

Objective To investigate the effect of NOD-like receptor family pyrin domain containing 3(NLRP3)knockdown on a mouse model of nonalcoholic steatohepatitis(NASH)induced by high-fat high-carbohydrate(HFHC)diet.Methods A total of 44 mice were randomly divided into normal diet group(CON group)with 20 mice and HFHC group with 24 mice.At the end of week 14 of modeling,4 mice were randomly selected from the HFHC group for the pre-experiment of adeno-associated virus(AAV)by tail vein injection,and NLRP3 knockdown was verified after 4 weeks.After NLRP3 knockdown was verified at the end of week 18,the remaining 40 mice were given a single tail vein injection of AAV,and then they were divided into CON+NLRP3 knockdown negative control group(CON+NLRP3-NC group),CON+NLRP3 knockdown group(CON+NLRP3-KD group),HFHC+NLRP3-NC group,and HFHC+NLRP3-KD group,with 10 mice in each group.At the end of week 24,the activation of NLRP3 inflammasome was observed;related indicators were measured,including body weight,liver weight,liver index,and glucose metabolism(fasting blood glucose,fasting insulin,and Homeostasis Model Assessment of Insulin Resistance[HOMA-IR]index);the indicators of liver lipid content(liver triglyceride[TG]and oil red O staining),liver inflammation(serum alanine aminotransferase[ALT]activity,HE staining,and inflammation-related genes),and liver fibrosis(Sirius Red staining and fibrosis-related genes)were measured.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the CON+NLRP3-NC group based on the results of Western Blot,the HFHC+NLRP3-NC group had significant increases in the protein expression levels of NLRP3,pro-Caspase1,Caspase1,ASC,and IL-1β,while the HFHC+NLRP3-KD group had significant reductions in these levels(all P<0.05).The HFHC+NLRP3-NC group showed varying degrees of increase in body weight,liver weight,liver index,and glucose metabolism indicators,while the HFHC+NLRP3-KD group showed significant improvements in these indicators(all P<0.05).As for hepatic fat deposition,compared with the CON+NLRP3-NC group,the HFHC+NLRP3-NC group had a significant increase in liver TG,with a large number of red lipid droplets shown by oil red O staining,and the HFHC+NLRP3-KD group had significant reductions in liver TG and the number of lipid droplets in the liver(all P<0.01).In terms of liver inflammation,compared with the CON+NLRP3-NC group,the HFHC+NLRP3-NC group had significant increases in serum ALT,NAFLD activity score,and inflammation-related genes,while the HFHC+NLRP3-KD group had significant reductions in these indicators(all P<0.01).As for liver fibrosis,compared with the CON+NLRP3-NC group,the HFHC+NLRP3-NC group had significant increases in collagen fiber area and fibrosis-related genes,and the HFHC+NLRP3-KD group had significant reductions in fibrosis-related genes(all P<0.05)and a tendency of reduction in collagen fiber area(P>0.05).Conclusion NLRP3 knockdown can significantly improve hepatic fat deposition and inflammation in a mouse model of HFHC-induced NASH.

METHODS: We retrospectively collected CT scan data from 276 patients with pathologically confirmed primary bone tumors from 4 medical centers in Guangdong Province between January, 2010 and August, 2021. A convolutional neural network (CNN) was employed as the deep learning architecture. The optimal baseline deep learning model (R-Net) was determined through transfer learning, and an optimized model (S-Net) was obtained through algorithmic improvements. Multivariate logistic regression analysis was used to screen the clinical features such as sex, age, mineralization location, and pathological fractures, which were then connected with the imaging features to construct the deep learning fusion model (SC-Net). The diagnostic performance of the SC-Net model and machine learning models were compared with radiologists' diagnoses, and their classification performance was evaluated using the area under the receiver operating characteristic curve (AUC) and F1 score. RESULTS: In the external test set, the fusion model (SC-Net) achieved the best performance with an AUC of 0.901 (95% CI: 0.803-1.00), an accuracy of 83.7% (95% CI: 69.3%-93.2%) and an F1 score of 0.857, and outperformed the S-Net model with an AUC of 0.818 (95% CI: 0.694-0.942), an accuracy of 76.7% (95% CI: 61.4%-88.2%), and an F1 score of 0.828. The overall classification performance of the fusion model (SC-Net) exceeded that of radiologists' diagnoses. CONCLUSIONS The deep learning fusion model based on multi-center CT images and clinical features is capable of accurate classification of osseous and chondroid matrix mineralization and may potentially improve the accuracy of clinical diagnoses of osteogenic versus chondrogenic primary bone tumors.
Humans ; Deep Learning ; Bone Neoplasms/diagnostic imaging* ; Retrospective Studies ; Tomography, X-Ray Computed/methods* ; Neural Networks, Computer ; Male ; Female ; ROC Curve ; Algorithms

Exosomes are membranous vesicles secreted by most eukaryotic cells, which are approximately 30-150 nm in diameter and contain RNA, proteins and lipids closely related to their function and origin, playing an important role in cell-to-cell communication. It can promote tumor progression by promoting the proliferation and migration of tumor cells, improving the tumor microenvironment and inhibiting the immune response. In addition, exosomes are expressed at high levels in certain tumors and can be used as predictors of cancer for early diagnosis. It can also be used as a carrier to carry targeted drugs to the local tumor to exert an inhibitory effect.

Objective: To investigate the factors affecting human papillomavirus (HPV) vaccination behaviors among gynecological outpatients based on extended unified theory of acceptance and use of technology (UTAUT2), so as to provide insights into the development of HPV vaccination behavioral interventions. Methods: Patients at ages of 45 years and younger that were admitted to the outpatient department of gynecological of Shanxi Provincial People's Hospital from October 2021 to August 2022 were recruited, and the factors affecting HPV vaccination behaviors were identified using UTAUT2. Results: A total of 431 female outpatients were enrolled, including 163 patients at ages of 36 to 45 years (37.82%), 272 cases with an educational level of college degree and above (63.11%) and 253 patients with per capita monthly household income of more than 3 000 Yuan (58.70%). The coverage of HPV vaccination was 24.36%, and the main cause of non-vaccination was difficulty in high-valent HPV vaccine appointment. Price value, social impact and efficacy expectation posed a positive impact on HPV vaccination behaviors via intention of vaccination (β=0.11, 0.08, 0.07, all P<0.05) and intention of vaccination and effort expectancy (β=0.10, 0.07, 0.06, all P<0.05), and effort expectancy played a mediating effect between intention of vaccination and vaccination behaviors (β=0.28, P<0.05). Conclusion Efficacy expectation, social impact, price value, intention of vaccination and effort expectancy may positively affect HPV vaccination behaviors.

Pyroptosis is a type of programmed cell death distincted from apoptosis and necrosis, which is accompanied by the lysis of cell membranes and the release of cell contents. Pyroptosis occurs as mediated by Gasdermin protein family and is dependent on the activity of caspase. GSDME is one of the most important members of the Gasdermin protein superfamily. GSDME-mediated pyroptosis relies on the activity of caspase-3. In recent years, with further research on pyroptosis, the mechanism of GSDME-induced pyroptosis is becoming clear. Numerous studies have shown that GSDME-mediated pyroptosis plays an important role in the occurrence and development of tumors, as well as chemotherapy resistance. However, GSDME-mediated pyroptosis has no specificity and can induce pyroptosis of normal cells in the body while inducing tumor cell pyroptosis, thus causing different degrees of damage to various organs of the body. Further study on the mechanism of GSDME-induced pyroptosis, the role of GSDME in malignant tumors and the adverse reactions of chemotherapy can provide new ideas for tumor monitoring, treatment and prognosis judgment.

Gasdermin E is closely related to neoplasms, which is involved in the occurrence and development of neoplasms through gene methylation, gene mutation or other ways. Pyroptosis mediated by gasdermin E is involved in drug therapy of various neoplasms, which provides a new theoretical basis for drug therapy of neoplasms. The study of gasdermin E aims to deepen the understanding of neoplasms and provide a new perspective for the prevention and treatment of neoplasms.