Metabolic associated fatty liver disease （MAFLD） is a chronic liver disease with a rapidly increasing incidence rate worldwide， and its complex pathogenesis is closely associated with O-linked β-N-acetylglucosamine （O-GlcNAc） modification. As a dynamic and reversible post-translational modification of proteins， O-GlcNAc modification is mainly regulated by O-GlcNAc transferase and O-GlcNAcase. O-GlcNAc modification can drive hepatic steatosis， exacerbate insulin resistance， and impair mitochondrial function， thereby leading to the aggravation of metabolic disorders， promoting inflammation response， and driving the progression of MAFLD to metabolic associated steatohepatitis and hepatic fibrosis. This article systematically reviews the latest research advances in the role of O-GlcNAc modification in the development and progression of MAFLD， in order to provide theoretical support and research direction for a deeper understanding of the pathological mechanism of MAFLD and the development of effective therapeutic strategies.

Structural optimization of lead compounds is a crucial step in drug discovery. One optimization strategy is to modify the molecular structure of a scaffold to improve both its biological activities and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. One of the deep molecular generative model approaches preserves the scaffold while generating drug-like molecules, thereby accelerating the molecular optimization process. Deep molecular diffusion generative models simulate a gradual process that creates novel, chemically feasible molecules from noise. However, the existing models lack direct interatomic constraint features and struggle with capturing long-range dependencies in macromolecules, leading to challenges in modifying the scaffold-based molecular structures, and creates limitations in the stability and diversity of the generated molecules. To address these challenges, we propose a deep molecular diffusion generative model, the three-dimensional (3D) equivariant diffusion-driven molecular generation (3D-EDiffMG) model. The dual strong and weak atomic interaction force-based long-range dependency capturing equivariant encoder (dual-SWLEE) is introduced to encode both the bonding and non-bonding information based on strong and weak atomic interactions. Additionally, a gate multilayer perceptron (gMLP) block with tiny attention is incorporated to explicitly model complex long-sequence feature interactions and long-range dependencies. The experimental results show that 3D-EDiffMG effectively generates unique, novel, stable, and diverse drug-like molecules, highlighting its potential for lead optimization and accelerating drug discovery.

Objective To analyze relevant literature on the essence of traditional Chinese medicine syndromes using bibliometric methods;To understand the current research status and hotspots in this field;To provide references for relevant research.Methods Research literature about the essence of TCM syndromes was retrieved from CNKI,VIP,Wanfang Data and CBM from 1st Jan.1979 to 30th June 2024.CiteSpace 6.2 software was used to conduct visualization analysis on authors,institutions,keywords,etc.Results A total of 695 articles were included,with an overall upward trend in publication volume followed by stabilization.The authors who published more articles included Luo Ren(13 articles),Zhao Xiaoshan(13 articles),Li Zegeng(12 articles),etc.The institutions with more publications included Shandong University of Traditional Chinese Medicine(35 articles),Beijing University of Chinese Medicine(33 articles),Chengdu University of Traditional Chinese Medicine(26 articles),etc.Institutions were clustered regionally,and cooperation was mostly between TCM universities and their affiliated hospitals,with less cross regional communication.High frequency keywords included kidney yang deficiency syndrome,metabolomics,animal models,TCM syndrome types,coronary heart disease,lung qi deficiency syndrome,spleen qi deficiency syndrome,liver depression and spleen deficiency syndrome,etc;Keyword clustering covered aspects such as biomolecules and metabolism,TCM syndromes,pathology,disease models,and animal research.Conclusion Research in the field of the essence of TCM syndromes is gradually receiving more attention.Exploring the essence of TCM syndromes at the molecular level through techniques such as genomics,transcriptomics,metabolomics and proteomics is a research hotspot and trend in this field.

Objective Based on data mining,network pharmacology,and molecular docking techniques,the medication patterns and underlying mechanisms of the therapeutic approach of trengthening the spleen,transforming stasis and removing toxins methods(JPHYJD)in treating gastric precancerous lesions(GPL)were analyzed.Methods Initially,data mining was conducted to extract relevant literature on the application of JPHYJD in GPL.An analytical network map was then constructed to get the identification of a representative drug set.In the network pharmacology phase.Active compounds and their targets were retrieved from TCMSP,while disease-related targets specific to GPL were sourced from Gene Cards,OMIM,and TTD.A"drug-disease"target intersection was mapped using bioinformatics platforms,and an"active compound-key target"network was constructed in Cytoscape.Protein-protein interaction(PPI)networks were obtained from the STRING database,and GO and KEGG enrichment analyses were performed to elucidate biological processes and pathways.Preliminary validation was conducted using molecular docking technology.Results 63 prescriptions were analyzed,with Baizhu-Ezhu-Danshen-Baihuashecao identified as the most representative drug set.85 active compounds and 590 predicted targets were discovered,intersecting with 4,726 disease-related targets,resulting in 412 key targets.GO and KEGG enrichment analyses yielded 3,541 enriched terms and 196 pathways,respectively.Key compounds,such as quercetin and alexandrin,targeted pivotal proteins like tumor protein 53(TP53),signal transducer and activator of transcription 3(STAT3),and epidermal growth factor receptor(EGFR)were implicated in regulating critical pathways like PI3K/AKT,exerting therapeutic effects.Molecular docking results demonstrated stable binding interactions between the core active compounds and their targets,reinforcing the predicted interactions.Conclusion This study,integrating data mining,network pharmacology,and molecular docking techniques,successfully elucidated the therapeutic patterns and underlying mechanisms of the JPHYJD approach in GPL treatment.

Structural optimization of lead compounds is a crucial step in drug discovery.One optimization strategy is to modify the molecular structure of a scaffold to improve both its biological activities and absorption,distribution,metabolism,excretion,and toxicity(ADMET)properties.One of the deep molecular generative model approaches preserves the scaffold while generating drug-like molecules,thereby accelerating the molecular optimization process.Deep molecular diffusion generative models simulate a gradual process that creates novel,chemically feasible molecules from noise.However,the existing models lack direct interatomic constraint features and struggle with capturing long-range dependencies in macromolecules,leading to challenges in modifying the scaffold-based molecular structures,and creates limitations in the stability and diversity of the generated molecules.To address these challenges,we propose a deep molecular diffusion generative model,the three-dimensional(3D)equivariant diffusion-driven molecular generation(3D-EDiffMG)model.The dual strong and weak atomic interaction force-based long-range dependency capturing equivariant encoder(dual-SWLEE)is introduced to encode both the bonding and non-bonding information based on strong and weak atomic interactions.Addi-tionally,a gate multilayer perceptron(gMLP)block with tiny attention is incorporated to explicitly model complex long-sequence feature interactions and long-range dependencies.The experimental results show that 3D-EDiffMG effectively generates unique,novel,stable,and diverse drug-like molecules,highlighting its potential for lead optimization and accelerating drug discovery.

Objective:This study aims to explore whether there are specific behavioral deficits of response inhibition and emotional processing in patients with checking obsessive-compulsive disorder (OCD) and those with washing OCD.Methods:A cross-sectional study was conducted from January 2020 to December 2022, collecting clinical data from 75 OCD patients at the outpatient psychological consultation clinic of Xiangya Second Hospital and the clinical psychology department of Hunan Brain Hospital. The sample included 40 OCD patients with checking type (checking group, 24 males, 16 females, aged 14-34 years, mean age 22.1±5.0 years) and 35 OCD patients with washing type (washing group, 12 males, 23 females, aged 14-41 years, mean age 22.6±6.7 years). An age-matched healthy control group (control group) of 80 individuals (HCs, 37 males and 43 females, aged 14-25 years, mean age 20.8±1.9 years) was also recruited. All participants completed the Go/No-go task and Hariri task with behavioral data recorded. The Dimensional Yale-Brown Obsessive-Compulsive Scale was used to assess the severity of OCD symptoms. The Center for Epidemiologic Studies Depression Scale (CES-D) and State Anxiety Inventory (STAI) were used to assess the severity of depression and anxiety. A 3 (group: checking OCD, washing OCD and HC)×2 (task type: Go vs. No-go/Shape vs. Face) repeated-measures ANOVA was conducted to compare the behavioral performance across tasks.Results:Compared with HC group, both checking OCD group and washing OCD group had significantly higher scores in depression and anxiety ( F=85.43, 32.33,both P<0.05). When performing Go/No-go task, a significant group×task interaction effect was observed ( F3(2, 152)=3.23, P3=0.042, partialη32=0.04). In the checking OCD group, No-go accuracy was significantly lower than Go accuracy (accuracy=0.821 vs. 0.893, P<0.001); the checking OCD had significantly lower accuracy than HC in the No-go task (accuracy=0.821 vs. 0.876, P=0.005); there were no significant group differences between the washing OCD and HC in the No-go task ( P>0.05). When performing Hariri task, a significant group×task interaction effect was found ( F3(2, 152)=4.91, P3=0.009, partial η32=0.06). The washing OCD group showed significantly lower accuracy in matching emotional faces than the control group (0.879 vs. 0.936, P=0.001), whereas the checking OCD group showed no significant difference from the HC ( P>0.05); there were no significant group differences in shape matching task ( P>0.05). The accuracy of shape matching task was significantly higher than face matching task in the three groups (shape: checking OCD=0.936,washing OCD=0.929,HC=0.943; face:checking OCD=0.877,washing OCD=0.844,HC=0.917;all P>0.05). Conclusions:Checking OCD and washing OCD exhibit distinct behavioral impairment patterns in response inhibition and emotional processing. Checking-type OCD is primarily characterized by impaired response inhibition, whereas washing-type OCD is mainly associated with deficits in emotion processing.

Objective Based on data mining,network pharmacology,and molecular docking techniques,the medication patterns and underlying mechanisms of the therapeutic approach of trengthening the spleen,transforming stasis and removing toxins methods(JPHYJD)in treating gastric precancerous lesions(GPL)were analyzed.Methods Initially,data mining was conducted to extract relevant literature on the application of JPHYJD in GPL.An analytical network map was then constructed to get the identification of a representative drug set.In the network pharmacology phase.Active compounds and their targets were retrieved from TCMSP,while disease-related targets specific to GPL were sourced from Gene Cards,OMIM,and TTD.A"drug-disease"target intersection was mapped using bioinformatics platforms,and an"active compound-key target"network was constructed in Cytoscape.Protein-protein interaction(PPI)networks were obtained from the STRING database,and GO and KEGG enrichment analyses were performed to elucidate biological processes and pathways.Preliminary validation was conducted using molecular docking technology.Results 63 prescriptions were analyzed,with Baizhu-Ezhu-Danshen-Baihuashecao identified as the most representative drug set.85 active compounds and 590 predicted targets were discovered,intersecting with 4,726 disease-related targets,resulting in 412 key targets.GO and KEGG enrichment analyses yielded 3,541 enriched terms and 196 pathways,respectively.Key compounds,such as quercetin and alexandrin,targeted pivotal proteins like tumor protein 53(TP53),signal transducer and activator of transcription 3(STAT3),and epidermal growth factor receptor(EGFR)were implicated in regulating critical pathways like PI3K/AKT,exerting therapeutic effects.Molecular docking results demonstrated stable binding interactions between the core active compounds and their targets,reinforcing the predicted interactions.Conclusion This study,integrating data mining,network pharmacology,and molecular docking techniques,successfully elucidated the therapeutic patterns and underlying mechanisms of the JPHYJD approach in GPL treatment.

Objective To analyze relevant literature on the essence of traditional Chinese medicine syndromes using bibliometric methods;To understand the current research status and hotspots in this field;To provide references for relevant research.Methods Research literature about the essence of TCM syndromes was retrieved from CNKI,VIP,Wanfang Data and CBM from 1st Jan.1979 to 30th June 2024.CiteSpace 6.2 software was used to conduct visualization analysis on authors,institutions,keywords,etc.Results A total of 695 articles were included,with an overall upward trend in publication volume followed by stabilization.The authors who published more articles included Luo Ren(13 articles),Zhao Xiaoshan(13 articles),Li Zegeng(12 articles),etc.The institutions with more publications included Shandong University of Traditional Chinese Medicine(35 articles),Beijing University of Chinese Medicine(33 articles),Chengdu University of Traditional Chinese Medicine(26 articles),etc.Institutions were clustered regionally,and cooperation was mostly between TCM universities and their affiliated hospitals,with less cross regional communication.High frequency keywords included kidney yang deficiency syndrome,metabolomics,animal models,TCM syndrome types,coronary heart disease,lung qi deficiency syndrome,spleen qi deficiency syndrome,liver depression and spleen deficiency syndrome,etc;Keyword clustering covered aspects such as biomolecules and metabolism,TCM syndromes,pathology,disease models,and animal research.Conclusion Research in the field of the essence of TCM syndromes is gradually receiving more attention.Exploring the essence of TCM syndromes at the molecular level through techniques such as genomics,transcriptomics,metabolomics and proteomics is a research hotspot and trend in this field.

Objective:This study aims to explore whether there are specific behavioral deficits of response inhibition and emotional processing in patients with checking obsessive-compulsive disorder (OCD) and those with washing OCD.Methods:A cross-sectional study was conducted from January 2020 to December 2022, collecting clinical data from 75 OCD patients at the outpatient psychological consultation clinic of Xiangya Second Hospital and the clinical psychology department of Hunan Brain Hospital. The sample included 40 OCD patients with checking type (checking group, 24 males, 16 females, aged 14-34 years, mean age 22.1±5.0 years) and 35 OCD patients with washing type (washing group, 12 males, 23 females, aged 14-41 years, mean age 22.6±6.7 years). An age-matched healthy control group (control group) of 80 individuals (HCs, 37 males and 43 females, aged 14-25 years, mean age 20.8±1.9 years) was also recruited. All participants completed the Go/No-go task and Hariri task with behavioral data recorded. The Dimensional Yale-Brown Obsessive-Compulsive Scale was used to assess the severity of OCD symptoms. The Center for Epidemiologic Studies Depression Scale (CES-D) and State Anxiety Inventory (STAI) were used to assess the severity of depression and anxiety. A 3 (group: checking OCD, washing OCD and HC)×2 (task type: Go vs. No-go/Shape vs. Face) repeated-measures ANOVA was conducted to compare the behavioral performance across tasks.Results:Compared with HC group, both checking OCD group and washing OCD group had significantly higher scores in depression and anxiety ( F=85.43, 32.33,both P<0.05). When performing Go/No-go task, a significant group×task interaction effect was observed ( F3(2, 152)=3.23, P3=0.042, partialη32=0.04). In the checking OCD group, No-go accuracy was significantly lower than Go accuracy (accuracy=0.821 vs. 0.893, P<0.001); the checking OCD had significantly lower accuracy than HC in the No-go task (accuracy=0.821 vs. 0.876, P=0.005); there were no significant group differences between the washing OCD and HC in the No-go task ( P>0.05). When performing Hariri task, a significant group×task interaction effect was found ( F3(2, 152)=4.91, P3=0.009, partial η32=0.06). The washing OCD group showed significantly lower accuracy in matching emotional faces than the control group (0.879 vs. 0.936, P=0.001), whereas the checking OCD group showed no significant difference from the HC ( P>0.05); there were no significant group differences in shape matching task ( P>0.05). The accuracy of shape matching task was significantly higher than face matching task in the three groups (shape: checking OCD=0.936,washing OCD=0.929,HC=0.943; face:checking OCD=0.877,washing OCD=0.844,HC=0.917;all P>0.05). Conclusions:Checking OCD and washing OCD exhibit distinct behavioral impairment patterns in response inhibition and emotional processing. Checking-type OCD is primarily characterized by impaired response inhibition, whereas washing-type OCD is mainly associated with deficits in emotion processing.

【Objective】 To study the effects of gestational diabetes (GDM) on morphological structure of brain tissue and microribonucleotide (miRNA) expression profile in neonatal mice, and to provide a new research target for the prevention and treatment of abnormal neurodevelopment in GDM progeny. 【Methods】 The pregnant mice were divided into model group and control group,each group consisted of 10 mice. The model group mice established a GDM model by injecting streptozotocin to measure fasting blood glucose (FPG) and random blood glucose (GLU) at different times. Successful molded mice were randomly divided into model group A and model group C, and control mice were divided into control group B and control group D, with 5 mice in each group. The newborn mice in groups A and B were used for hippocampal tissue GeneChip detection and brain morphology structure observation, and group C and D newborn mice were used for qRT-PCR detection of hippocampus tissue expression differences to verify the differentially expressed genes of miRANs obtained by GeneChip screening. After giving birth, the neonatal mice were sacrificed by decapitation, and the brain tissue was dissected to observe the overall morphological structure. The structural changes of hippocampus were observed under HE chromogenic microscope. The Agilent mouse miRNA oligonucleotide gene chip was used to detect the miRNA expression profile of mouse hippocampus, screen differential miRNAs and predict their target genes, and conduct GO analysis and signal transduction pathway analysis of target genes. The relative expression levels of the screened miRNAs were verified by qRT-PCR. 【Results】 Compared with the control group, the GLU increased significantly from the 3rd day after drug administration in the model group (P<0.01). Macroscopic observation of control group B mice had normal brain morphology and structure, smooth appearance, clear gyrus, close arrangement of hippocampus cell structure, uniform staining and complete structure; in model group A, the number of hippocampus cells decreased, loose arrangement and deep staining. In the initial screen of miRNA microarray, there were 11 differentially expressed miRNAs between control and model groups, all of which were downregulated miRNAs, including let-7b-5p、miR-130b-3p、miR-181c-5p、miR-181d-5p、miR-3099-3p、miR-3470a、miR-3473a、miR-3473b、miR-500-3p、miR-532-5p、miR-7047-5p(P<0.05). Two miRNAs (miR-3473b, miR-7047-75p) and 5 target genes (MAPK3, MAPK11, MAPK14, CALM3, AKT3). The relative expression of miR-3473b and miR-7047-5p in model group C were lower than that in control group D (t=19.13 and 6.24, P<0.05), and the validation results were consistent with the microarray test results. 【Conclusion】 Compared with the offspring of normal pregnant mice, GDM offspring mice have abnormal development of brain structure and damage of hippocampal nerve cells, and there are a large number of abnormal expression of miRNAs in hippocampal tissue. Differentially expressed miRNAs can be used as research targets for prevention and treatment of GDM offspring neurodevelopmental abnormalities.