ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure （HF）， providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine （TCM）. MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats， which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group， with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry （UPLC-TQ-S）， and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging （AFADESI-MSI）. Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus （GEO）， a protein-protein interaction （PPI） network was constructed， and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway and Gene Ontology （GO） was performed. Finally， molecular docking was conducted to verify the binding between core metabolic components and key targets， and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group， the levels of arginine and citrulline in the serum of model rats were significantly decreased （P<0.01）， while those of proline， ornithine， creatine， creatinine and glutamate were significantly increased （P<0.05， P<0.01）. Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets， such as the angiotensin-converting enzyme （ACE）， neuronal nitric oxide synthase （NOS1）， 5-hydroxytryptamine receptor 2A （HTR2A）， and epidermal growth factor receptor （EGFR）， and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway， neuroactive ligand-receptor interactions， and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine， citrulline and HTR2A， as well as between creatine， creatinine and EGFR. Based on pathway-target prediction， potential TCM interventions， such as ginseng and magnolia， were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF， and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways， and offers valuable insights for targeted therapy of HF and the development of TCM.

ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure （HF）， providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine （TCM）. MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats， which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group， with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry （UPLC-TQ-S）， and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging （AFADESI-MSI）. Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus （GEO）， a protein-protein interaction （PPI） network was constructed， and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway and Gene Ontology （GO） was performed. Finally， molecular docking was conducted to verify the binding between core metabolic components and key targets， and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group， the levels of arginine and citrulline in the serum of model rats were significantly decreased （P<0.01）， while those of proline， ornithine， creatine， creatinine and glutamate were significantly increased （P<0.05， P<0.01）. Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets， such as the angiotensin-converting enzyme （ACE）， neuronal nitric oxide synthase （NOS1）， 5-hydroxytryptamine receptor 2A （HTR2A）， and epidermal growth factor receptor （EGFR）， and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway， neuroactive ligand-receptor interactions， and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine， citrulline and HTR2A， as well as between creatine， creatinine and EGFR. Based on pathway-target prediction， potential TCM interventions， such as ginseng and magnolia， were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF， and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways， and offers valuable insights for targeted therapy of HF and the development of TCM.

O-GlcNAc glycosylation， as the most extensive type of glycosylation modification， is involved in the development and prognosis of ischemic stroke by regulating excitatory toxicity， mitochondrial function， synaptic plasticity， and immune metabolism and inhibiting endoplasmic reticulum stress and inflammatory response， and regulation of O-GlcNAc glycosylation is considered a promising therapeutic target for ischemic stroke.This article reviews the characteristics and specific mechanisms of O-GlcNAc glycosylation in ischemic stroke，in order to provide new ideas for the prevention and treatment of ischemic stroke.
Glycosylation

Intestinal fibrosis is a major complication of inflammatory bowel disease (IBD), leading to a high incidence of surgical interventions and significant disability. Despite its clinical relevance, no targeted pharmacological therapies are currently available. This review aims to explore the underlying mechanisms driving intestinal fibrosis and address unresolved scientific questions, offering insights into potential future therapeutic strategies. We conducted a literature review using data from PubMed up to October 2024, focusing on studies related to IBD and fibrosis. Intestinal fibrosis results from a complex network involving stromal cells, immune cells, epithelial cells, and the gut microbiota. Chronic inflammation, driven by factors such as dysbiosis, epithelial injury, and immune activation, leads to the production of cytokines like interleukin (IL)-1β, IL-17, and transforming growth factor (TGF)-β. These mediators activate various stromal cell populations, including fibroblasts, pericytes, and smooth muscle cells. The activated stromal cells secrete excessive extracellular matrix components, thereby promoting fibrosis. Additionally, stromal cells influence the immune microenvironment through cytokine production. Future research would focus on elucidating the temporal and spatial relationships between immune cell-driven inflammation and stromal cell-mediated fibrosis. Additionally, investigations are needed to clarify the differentiation origins of excessive extracellular matrix-producing cells, particularly fibroblast activation protein (FAP) + fibroblasts, in the context of intestinal fibrosis. In conclusion, aberrant stromal cell activation, triggered by upstream immune signals, is a key mechanism underlying intestinal fibrosis. Further investigations into immune-stromal cell interactions and stromal cell activation are essential for the development of therapeutic strategies to prevent, alleviate, and potentially reverse fibrosis.
Humans ; Fibrosis/metabolism* ; Inflammatory Bowel Diseases/pathology* ; Animals ; Transforming Growth Factor beta/metabolism* ; Intestines/pathology*

As a typical "double heart" disease, the incidence rate of coronary heart disease with anxiety and depression is increasing year by year, which affects the long-term prognosis of the disease and the quality of life of patients. Based on the holistic concept of TCM, the theory of "heart-gallbladder connection" holds that there is a physiological and pathological relationship between the heart and gallbladder. At the same time, the theory of "heart-gallbladder connection" combined with modern medicine points out that disturbances in bile acid metabolism, gallbladder heart reflex, and brain gut bile acid axis are the three key nodes in the development of anxiety and depression in coronary heart disease. Starting from the theory of "heart-gallbladder connection", coronary heart disease combined with anxiety and depression is divided into three syndromes: heart deficiency and timidity, heart gallbladder stagnation, and heart gallbladder fire hyperactivity. Taking the principle of heart gallbladder harmony, the treatment of nourishing the heart and warming the gallbladder, regulating the heart and clearing the gallbladder, and clearing the heart and promoting bile flow is applied to provide a new clinical diagnosis and treatment approach for coronary heart disease combined with anxiety and depression.

Objective To clarify the active ingredients and the potential molecular mechanism of Guben Qushi Huayu Prescription in treating psoriasis recurrence.Methods An ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was applied to analyze the whole formula and the constituents absorbed into blood of Guben Qushi Huayu Prescription,and molecular docking technology was used to study the binding affinity of the constituents absorbed into blood with psoriasis-related immunomodulatory proteins such as CD69 and CD103 proteins.Results Mass spectrometry analysis identified 21 active ingredients such as paeoniflorin in Guben Qushi Huayu Prescription,including several known anti-inflammatory and immunomodulatory compounds.Analysis of the constituents absorbed into blood identified 11 ingredients,including paeoniflorin,that may affect the course of psoriasis through blood circulation.Molecular docking studies revealed that the constituents absorbed into blood,including astilbin,isoastilbin,chlorogenic acid,neochlorogenic acid,cryptochlorogenic acid,helicine,paeoniflorin,ononin,all had high binding affinities with CD69 and CD103 proteins.Conclusion This research reveals the main active ingredients of Guben Qushi Huayu Prescription and their potential mechanism for regulating the recurrence of psoriasis by mass spectrometry and molecular docking technology,contributing to providing scientific basis for further pharmacological research and clinical application.

Objective : To investigate the impact of fecal microbiota transplantation (FMT) on the composition of 15 intestinal-derived estrogens and their metabolites (EMs) and its correlation with non-alcoholic fatty liver disease (NAFLD) . Methods: Thirty male C57BL/6J mice were divided into a normal control group (Control) , a high- sugar high-fat diet combined with low-dose CCl4 -induced NAFLD model group ( Model) , and a group of model mice treated with fecal microbiota from normal female mice (FMT) . After 17 weeks of modeling , liver pathology in each group was observed using HE staining , biochemical methods were used to measure serum alanine aminotrans- ferase (ALT) and aspartate aminotransferase (AST) levels , as well as hepatic triglyceride (TG) and total choles- terol (TC) levels. and the content of 15 EMs in portal vein serum was detected using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS) . The correlation between disease phenotype and intesti- nal EMs was analyzed using Pearson ′s method. Results: The NAFLD model was successfully established , and the FMT group showed improved liver structure and morphology , with significant decreases in liver function and hepatic lipids compared to the Model group. In NAFLD mice , the contents of E1 , E2 , and their 2- and 4-position metabo- lites in portal vein blood serum was reduced compared to normal mice , while the content of most 16- and 17-posi- tion metabolites ( except 16α-OHE1) increased compared to normal mice. Correlation analysis showed that ALT was strongly positively correlated with E3 and 17-epiE3 , and strongly negatively correlated with E1 , E2 , 4- MeOE1 , and 16α-OHE1 . The TC was strongly positively correlated with 17-epiE3 and strongly negatively correla- ted with E1 , 4-MeOE1 , and 16α-OHE1 . Conclusion FMT restores the disrupted composition of intestinal EMs and improves NAFLD.

OBJECTIVE: To explore the clinical phenotypes and genetic characteristics of a child with Acid-labile subunit deficiency (ALS). METHODS: A male child diagnosed with ALS at Dongguan Maternal and Child Health Care Hospital in March 2021 was selected as the study subject. Clinical data of his family was collected. Peripheral blood samples were collected from the child and his parents. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out, and Sanger sequencing was used for family verification of candidate variants. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of the candidate variant was classified. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2020-6). RESULTS: The patient, a 5-year-and-7-month-old boy, presented with short stature and delayed bone age. Endocrine examinations showed decreased serum concentrations of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP3). WES revealed that he has harbored compound heterozygous variants of the IGFALS gene, namely c.741_742del, p.Y248Pfs83 and c.272del, p.P91Rfs31. Sanger sequencing verified that the variants were inherited from his father and mother, respectively. According to the ACMG guidelines, c.741_742del, p.Y248Pfs83 and c.272del, p.P91Rfs31 variants were classified as likely pathogenic (PVS1+PM2_supporting). Based on the pre-set literature search strategy, 11 research literature on ALS were retrieved, which involved a total of 33 families and 62 patients. Combined with the patient in this study, 31 IGFALS gene variants were identified among the 63 patients, which mainly consisted of missense variants (20 types), with variant sites concentrated in exon 2. The main clinical features were short stature in conjunct with delayed puberty, with a significant genotype-phenotype correlation. CONCLUSION The IGFALS gene variants NM_004970.2: c.741_742del, p.Y248Pfs83 and c.272del, p.P91Rfs31 may be the genetic etiology in this family. This study has expanded the variant spectrum of the IGFALS gene and provided valuable information for the diagnosis, genetic counseling and clinical treatment of the disease.
Humans ; Male ; Phenotype ; Child, Preschool ; Carrier Proteins/genetics* ; Glycoproteins/deficiency* ; Exome Sequencing ; Female ; Mutation ; Insulin-Like Growth Factor I/metabolism* ; Growth Disorders/genetics*

Objective:To explore the effects of online mindfulness-based stress reduction(MBSR)on the anxiety and depression status,and quality of life in the caregivers of patients with severe mental disorders.Methods:Ninety-three caregivers for patients with schizophrenia or bipolar disorder,who were hospitalized in Yunnan Provincial Mental Hospital in March 2021,were enrolled and randomly divided into control group(n=47)and MBSR intervention group(n=46).Both groups received basic health education and rehabilitation skill training,while the intervention group received additional online MBSR for 8 weeks.The anxiety and depression status,and the quality of life of the caregivers were evaluated by Self-rating Anxiety Scale(SAS),Self-rating Depression Scale(SDS)and the 36-item Short Form Health Survey(SF-36)before and 8 weeks after intervention,respectively.Results:Thirteen caregivers dropped out of the study,and 80 subjects(40 in each group)were included in the final analysis.At the baseline,there were no significant differences in SAS,SDS and SF-36 scores between two groups(all P>0.05).Compared with the baseline,SAS and SDS scores in the intervention group significantly decreased after 8 weeks of intervention(both P<0.01)and were significantly lower than those in the control group(both P<0.01).There were no significant changes in the control group(all P>0.05).Except the physiological function dimension,the total score and the scores of each dimension of SF-36 in the intervention group were significantly increased after 8-week intervention(all P<0.05),and were significantly higher than those in the control group(all P<0.01).There were no significant changes in the control group before and after intervention(all P>0.05).Conclusion:Online MBSR can reduce the anxiety and depression levels,improve the quality of life in the caregivers of patients with severe mental disorders.

Objective To investigate the efficacy of Jianpiwenyang Gel(SSWYG)for treating chronic diarrhea and explore its therapeutic mechanism.Methods Eighty patients with chronic diarrhea of spleen and stomach weakness type were randomized into two groups for interventions with lifestyle adjustment and treatment with bifid triple viable capsules(control group,n=40)or naval application with SSWYG(treatment group,n=40)for one week,after which symptoms of chronic diarrhea were evaluated.The Chinese medicine system pharmacology analysis platform(TCMSP),GeneCards,NCBI,OMIM database and GEO database(GSE14841)were used to obtain the active ingredients and target proteins of SSWYG and chronic diarrhea-related targets.The key targets were obtained by topological analysis for Gene Ontology(GO)and KEGG analyses.The affinity and binding characteristics of SSWYG for specific targets were verified by molecular docking using AutoDock software.Results In both groups,gastrointestinal symptom rating scale(GSRS),Bristol Scale and TCM syndrome scores significantly improved after the treatments(P<0.05),and better effects were observed in the treatment group(P<0.05).Sixty-eight targets of SSWYG in treating chronic diarrhea were obtained,and 33 most probable ones were screened out by topological analysis.GO and KEGG analyses identified several chronic diarrhea-related pathways including the TNF and IL-17 pathways.Molecular docking study showed good affinity of the core components of SSWYG for the key targets CASP3,JNK,IL1B,IL6,and AKT1.JUN and CASP3 had the lowest binding energy and the highest stable binding energy with multiple major active ingredients of SSWYG.Conclusion SSWYG can significantly improve clinical symptoms of chronic diarrhea possibly by regulating the TNF and IL-17 as well as other pathways via CASP3 and JUN,suggesting a complex therapeutic mechanism of SSWYG involving multiple ingredients and targets and coordinated regulation of multiple pathways.