In 2023， multiple international societies proposed the concept of metabolic-dysfunction and alcohol-associated liver disease （MetALD） to characterize patients with steatotic liver disease who exhibit metabolic dysfunction and consume alcohol at a moderate level. In recent years， the evidence system in this field has been constantly developed and improved. This article reviews the latest research advances in MetALD from the aspects of background， definition， epidemiological characteristics， natural history， clinical phenotype， diagnostic and assessment methods， and treatment regimens， as well as the directions for future investigation.

Vast majority of human RNA are non-coding RNA(ncRNA),which can regulate physiological activities and affects functions on cells.Although each part of them is obscure,they are involved in different levels of gene regulation,from epigene-tic gene silencing to post transcriptional regulation.Metabolic reprogramming of tumor-associated macrophages(TAMs)can promote tumor progression and is closely related to activation phenotypes of anti-tumor(M1)or pro-tumor(M2).A lot of ncRNAs are involved in metabolic reprogramming of TAMs,reshaping tumor microenvironment and playing a key role in tumor progression.Improving understanding of effect on ncRNA regulating metabolic reprogramming of TAMs may provide new methods for developing effective clinical treatments.

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.

To review the randomized controlled trials (RCTs) at home and abroad on digital intelligence (DI)-driven rehabilitation in patients of neuromuscular disease, compare the effects of DI-driven rehabilitation with traditional rehabilitation, summarize the special needs and challenges faced by patients in rehabilitation of rare neuromuscular diseases, and provide evidence for the development and quality improvement of rehabilitation for rare neuromuscular diseases.

To provide references to and give suggestions to the development and optimiza-tion of Digital Intelligence (DI) technology in management of non-hospitalized patients by systematical review the application of digital technology in non-hospital settings.

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.

Vast majority of human RNA are non-coding RNA(ncRNA),which can regulate physiological activities and affects functions on cells.Although each part of them is obscure,they are involved in different levels of gene regulation,from epigene-tic gene silencing to post transcriptional regulation.Metabolic reprogramming of tumor-associated macrophages(TAMs)can promote tumor progression and is closely related to activation phenotypes of anti-tumor(M1)or pro-tumor(M2).A lot of ncRNAs are involved in metabolic reprogramming of TAMs,reshaping tumor microenvironment and playing a key role in tumor progression.Improving understanding of effect on ncRNA regulating metabolic reprogramming of TAMs may provide new methods for developing effective clinical treatments.

[Objective]To discuss the occurrence and gastric cancer accompanied by depression from the perspective of"depression caused by illness"and"illness caused by depression",and provide theoretical support for the treatment by traditional Chinese medicine(TCM).[Methods]By consulting the ancient and modern literature of TCM,and collecting the academic views of some doctors on the theory of"depression caused by illness"and"illness caused by depression"of gastric cancer,combined with clinical practice experience,it discusses the diagnosis and treatment of gastric cancer accompanied by depression.[Results]The etiology and pathogenesis of gastric cancer accompanied by depression can be summarized as follows:loss of middle Qi,the rise and fall of surly for its root;cementation of stasis and toxin,seven emotions disorder is its root;tumor gathering locally,poison overflowing into the blood vessels,illness and depression intermingled as its symptom,and it accordingly points out that the treatment of gastric cancer accompanied by depression should mediate middle Qi and smooth the Qi transformation of spleen and stomach;regulate Qi and open depression,regulate the rise and fall of Qi of the body;remove blood stasis and detoxify,dredge the body's Qi,blood and body fluid;form and spirit in tune,restore the complex of the five viscera of the human body.[Conclusion]Stasis,toxin and depression are important pathological factors affecting the occurrence,development and outcome of gastric cancer accompanied by depression.These three factors often affect each other as causation.Discussion of gastric cancer accompanied by depression from the perspective of"depression caused by illness"and"illness caused by depression"is not only helpful to improve the etiological and pathogenesis theory of gastric cancer accompanied by depression,but also helpful to provide theoretical reference for its clinical treatment.

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.