ObjectiveTo investigate the material basis and mechanism of action of Tuoli Xiaodu San in treating ulcerative colitis （UC） by integrating transcriptomics， network pharmacology， and experimental validation. MethodsNetwork pharmacology was initially employed to screen the active components and potential mechanisms of Tuoli Xiaodu San for treating UC. A UC mouse model was established by dextran sulfate sodium （DSS） induction. The mice were divided into the following groups： normal， model， high-dose （11.3 g·kg^-1） Tuoli Xiaodu San， low-dose （5.7 g·kg^-1） Tuoli Xiaodu San， and positive control （mesalazine， 0.4 g·kg^-1）. Intragastric administration commenced on day 1 of modeling and continued for 7 consecutive days. The disease activity index （DAI） was assessed daily. Hematoxylin-eosin （HE） staining was used to observe colonic pathological changes. Serum levels of tumor necrosis factor-alpha （TNF-α）， interleukin-1 beta （IL-1β） and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay （ELISA）. Transcriptome sequencing was performed on mouse colonic tissues， and the results were integrated with network pharmacology findings for in-depth analysis of Tuoli Xiaodu San's potential mechanisms in treating UC. Finally， the expression of key genes and proteins in the identified signaling pathways were detected using Western blot and Real-time polymerase chain reaction （Real-time PCR）. ResultsThe combined analysis of network pharmacology and transcriptomics results showed that the multi-pathway network with phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway as its core was the key mechanism of Tuoli Xiaodu San in the treatment of UC. Tuoli Xiaodu San administration significantly ameliorated weight loss， diarrhea， and bloody stools in UC mice， reduced the DAI scores （P<0.05， P<0.01）， lowered the colonic histopathological scores （P<0.01）， alleviated colon shortening （P<0.01）， and downregulated serum levels of TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01）. Molecular biology experiments confirmed that Tuoli Xiaodu San significantly inhibited the mRNA and protein expression， as well as the phosphorylation levels， of PI3K， Akt， and p65 in colonic tissues （P<0.05， P<0.01）. ConclusionTuoli Xiaodu San can regulate the multi-pathway network with PI3K/Akt as its core through multi-component synergy， thereby reducing colonic inflammatory damage and exerting a therapeutic effect on UC.

OBJECTIVES: To investigate the effect of cardiomyocytes-derived exosomes on lipopolysaccharide (LPS)-induced cardiomyocyte injury and its mechanism. METHODS: Exosomes isolated from rat cardiomyocytes with or without LPS treatment were co-cultured with rat lymphocytes. The lymphocytes with or without exosome treatment were co-cultured with LPS-induced rat cardiomyocytes for 48 h. Cardiomyocyte apoptosis was detected using flow cytometry, and the expressions of apoptosis marker proteins and the PI3K/AKT pathway proteins were detected using Western blotting. The effects of human recombinant IL-38 protein on apoptosis and protein expressions in LPS-induced cardiomyocytes were examined. RESULTS: Compared with normal cardiomyocyte-derived exosomes, the exosomes from LPS-induced cardiomyocytes significantly enhanced proliferation and increased mRNA and protein expression levels of IL-38 in rat lymphocytes. Bioinformatics analysis suggested that miR-1275 in the exosome played a key role in LPS-induced cardiomyocyte injury, and in dual luciferase reporter gene assay, miR-1275 mimics significantly increased luciferase activity of WT-IL-38. Co-culture with lymphocytes treated with exosomes from LPS-induced cardiomyocytes significantly inhibited apoptosis of LPS-induced cardiomyocytes. Treatment with recombinant IL-38 also effectively lowered apoptosis rate of LPS-induced cardiomyocytes, reduced cellular expression of Bax protein, and increased the protein expression levels of Bcl-2, p-PI3K and p-AKT. CONCLUSIONS miR-1275 in exosomes derived from LPS-induced cardiomyocytes mediates IL-38 up-regulation expression in lymphocytes to activate the PI3K/AKT pathway and inhibit LPS-induced cardiomyocyte apoptosis.
Apoptosis/drug effects* ; MicroRNAs/metabolism* ; Myocytes, Cardiac/metabolism* ; Animals ; Lipopolysaccharides ; Rats ; Exosomes/metabolism* ; Up-Regulation ; Interleukins/metabolism* ; Lymphocytes/cytology* ; Cells, Cultured ; Signal Transduction ; Coculture Techniques ; Phosphatidylinositol 3-Kinases/metabolism* ; Rats, Sprague-Dawley ; Humans ; Proto-Oncogene Proteins c-akt/metabolism*

Cholesterol is an essential molecule for the biosynthesis of cell membranes and cell proliferation and differentiation， and the liver plays a central role in cholesterol metabolism and is responsible for the synthesis， uptake， secretion， and transport of cholesterol. The initial stages of cholesterol synthesis in the liver are particularly important， and abnormalities in such stages are closely associated with the progression of various liver diseases. Studies have shown that as a key rate-limiting enzyme in cholesterol biosynthesis， 3-hydroxy-3-methylglutaryl-coenzyme A reductase （HMGCR） has well-defined regulatory properties and has been confirmed as an important target for the regulation of various liver diseases. This article reviews the process of cholesterol metabolism， the degradation and regulatory mechanisms of HMGCR， and the application of inhibitors， as well as the role of HMGCR in liver diseases， in order to provide new insights for scientific research and the clinical prevention and treatment of liver diseases.

Alzheimer's disease(AD), a neurodegenerative disorder associated with aging, is the most prevalent form of dementia.As the aging population continues to expand, AD presents significant health and caregiving challenges for families and society, making it a pressing international public health concern.In recent years, numerous countries have implemented dementia prevention and treatment strategies that emphasize community-based comprehensive approaches.Currently, the community-based AD prevention and treatment model in China is still in the exploratory phase, with community efforts lacking organization.In alignment with China's action plan for advancing dementia prevention and treatment, and to achieve the strategic objective of "healthy aging, " this consensus is based on the principle of three-level prevention and is tailored to the characteristics of AD disease progression.It aims to develop a comprehensive prevention and treatment strategy for AD that is suitable for communities in China, providing technical guidance and support to establish a scientific basis for formulating community AD prevention and treatment models.

Objective:To explore the impulsivity characteristics of patients with attention deficit hyperactivity disorder(ADHD)comorbid with borderline personality disorder(BPD)and the mediating role of emotion regula-tion strategies.Methods:A total of 96 patients with ADHD meeting the diagnostic criteria of the American Diagnos-tic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)were enrolled,48 of whom had comorbid BPD.Impulsivity was assessed with the Barratt Impulse Scale(BIS)and the impulse control difficulty dimensions of Emotional Regulation Difficulty Scale(DERS).Emotion regulation strategies were evaluated with the Emotion Regulation Questionnaire(ERQ).Results:No significant differences were found between the ADHD with and with-out BPD group in cognitive impulsivity,motor impulsivity,or non-planning impulsivity as assessed with the BIS(Ps＞0.05).However,the ADHD with BPD group showed higher scores on the DERS impulse control difficulty subscale(P＜0.001)and less frequent use of cognitive reappraisal strategies(P＜0.001).Cognitive reappraisal partially mediated the relationship between ADHD with BPD and impulse control difficulties,with an effect size of 25.9％.Conclusion:ADHD patients comorbid with BPD exhibit heightened emotional impulsivity,which might be partially mediated by reduced use of cognitive reappraisal.

BACKGROUND:Cervical rotation-traction manipulation is effective and safe in the treatment of cervical spondylotic radiculopathy,and has been widely used in clinical work.However,its effects on the biomechanics of cervical vertebra and intervertebral disc and the area of intervertebral foramen have not been systematically clarified. OBJECTIVE:Based on the finite element analysis technique,a relevant research and analysis were carried out to provide digital evidence for the mechanism of effect of cervical rotation-traction manipulation in the treatment of cervical spondylotic radiculopathy. METHODS:The CT image data of a volunteer with no neck diseases were selected as the finite element model material at its left-handed physiological limit position.The initial construction of the finite element model was completed by Mimics 19.0 software,Geomagic Studio 2013 software,Hypermash 14.0 software,and ANSYS Workbench 2020 R2 software,respectively.Based on the literature,the grid division of cervical structure and the assignment of elastic modulus and elastic coefficient were completed.Based on the previous work of the team,the mechanical effects of cervical rotation-traction manipulation were simulated on the model.Effects of cervical rotation-traction manipulation on the mechanical parameters of each vertebral body and intervertebral disc in C3-T1 segment and on the cervical lateral foramen area were analyzed. RESULTS AND CONCLUSION:(1)During cervical rotation-traction manipulation,the stress of bone structure was significantly higher than that of soft tissue such as intervertebral disc.(2)When operating the technique,the stress at the top of each cervical vertebra was higher,the stress at the bottom was lower,and the stress at the facet joint and transverse process was lower.The stress at the top of the intervertebral disc was lower,the stress at the bottom was higher,but the highest point of the intervertebral disc stress was outside the top.(3)In addition,after loading the lifting force,the projected area of the C6/C7 intervertebral foramen increased significantly compared with that before loading.(4)It is indicated that the cervical rotation-traction manipulation has the mechanical characteristics of changing the stress structure of the cervical spine itself,and can expand the C6/7 intervertebral cervical foramen area on the opposite side of the patient's cervical rotation,so as to achieve the purpose of treating cervical spondylotic radiculopathy.

Objective To investigate the effect of microRNA-146a-5p(miR-146a-5p)on high glucose-induced injury of renal tubular epithelial cells by regulating high mobility group A2(HMGA2).Methods Human renal tubular epithelial cells(HK-2)were cultured in vitro and di-vided into different groups according to various treatment methods:normal control group(Con group),high glucose group(HG group),HG+miR-146a-5p group,HG+si-HMGA2 group,HG+miR-146a-5p+pcDNA-HMGA2 group,miR-NC group,miR-146a-5p group,anti-miR-NC group,and anti-miR-146a-5p group.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the expression levels of miR-146a-5p and HMGA2 mRNA in each group.A dual-luciferase reporter assay was employed to verify the targeting relationship between miR-146a-5p and HMGA2.Western blot was utilized to detect the expression levels of cleaved-caspase3,cleaved-caspase9,and HMGA2 protein in each group.Flow cytometry was applied to determine the apoptosis rate of cells in each group.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of inflam-matory factors[interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interleukin-8(IL-8)]in each group.The levels of oxidative stress indicators[catalase(CAT),superoxide dismutase(SOD),malondialdehyde(MDA)]in each group were also measured.Results A nucleotide se-quence complementary to miR-146a-5p was found in the 3'-untranslated region(3'-UTR)of HMGA2.The expression level of HMGA2 protein in the miR-146a-5p group was lower than that in the miR-NC group,while was higher in the anti-miR-146a-5p group than that in the anti-miR-NC group(P＜0.05).The total apoptosis rate,early apoptosis rate,late apoptosis rate,and the levels of cleaved-caspase3 protein,cleaved-caspase9 protein,HMGA2 mRNA,HMGA2 protein,TNF-α,IL-6,IL-8,and MDA in the HG group were higher than those in the Con group,whereas the levels of miR-146a-5p,CAT,and SOD were lower(P＜0.05).In the HG+miR-146a-5p group,these indicators showed opposite trends compared to the HG group(P＜0.05).Similarly,in the HG+si-HMGA2 group,the total apoptosis rate,early apoptosis rate,late apoptosis rate,and the levels of cleaved-caspase3 protein,cleaved-caspase9 protein,HMGA2 mRNA,HMGA2 protein,TNF-α,IL-6,IL-8,and MDA were lower than those in the HG group,while the levels of CAT and SOD were higher(P＜0.05).In the HG+miR-146a-5p+pcDNA-HMGA2 group,the trends of these indicators were consistent with those between the HG group and the HG+miR-146a-5p group,showing statistically significant differences when compared to the HG+miR-146a-5p group(P＜0.05).Conclusion MiR-146a-5p may play a regulatory role in high glucose-induced injury of re-nal tubular epithelial cells by targeting HMGA2.

Objective To analyze the differences in cerebral blood flow(CBF)characteristics among children with different subtypes of attention deficit and hyperactivity disorder(ADHD)and their relationship with executive function using arterial spin labeling(ASL)technology.Methods A case-control study was conducted,including children diagnosed with ADHD at the outpatient clinic of Peking University Sixth Hospital from July 2015 to December 2019 as the ADHD group,and typically developing schoolchildren from January to December 2021 as the healthy control group.Both groups underwent pseudo-continuous ASL(pCASL)scanning to measure CBF,and executive function was assessed using the parent version of the Behavior Rating Inventory of Executive Function(BRIEF).Differences in CBF between ADHD children and healthy controls were com-pared.For brain regions showing significant group differences,CBF values were extracted and linear regression models were constructed with BRIEF scores to further explore the relationship between regional CBF and execu-tive function.Results A total of 134 boys with ADHD were included[83 with ADHD predominantly inat-tentive subtype(ADHD-Ⅰ)and 51 with ADHD combined subtype(ADHD-C)],along with 25 healthy control boys.Intergroup comparisons revealed that the CBF in the left middle temporal gyrus was significantly lower in ADHD-C children compared to both ADHD-Ⅰ children(P=0.010)and healthy controls(P＜0.001),while no significant difference was observed between ADHD-Ⅰ children and healthy controls(P=0.280).After adjusting for age and total IQ scores,the linear regression model showed that the CBF in the left middle temporal gyrus of ADHD-C children was negatively correlated with the planning/organization score on the BRIEF(β=-0.062,P=0.030).Conclusions The CBF in the left middle temporal gyrus of boys with ADHD-C is significantly lower than that of boys with ADHD-Ⅰ and healthy controls.This reduced regional CBF may be associated with executive function deficits in organization and planning abilities in ADHD-C,providing new insights into the neurobiological mechanisms underlying ADHD subtypes.

Cholesterol is an essential molecule for the biosynthesis of cell membranes and cell proliferation and differentiation,and the liver plays a central role in cholesterol metabolism and is responsible for the synthesis,uptake,secretion,and transport of cholesterol.The initial stages of cholesterol synthesis in the liver are particularly important,and abnormalities in such stages are closely associated with the progression of various liver diseases.Studies have shown that as a key rate-limiting enzyme in cholesterol biosynthesis,3-hydroxy-3-methylglutaryl-coenzyme A reductase(HMGCR)has well-defined regulatory properties and has been confirmed as an important target for the regulation of various liver diseases.This article reviews the process of cholesterol metabolism,the degradation and regulatory mechanisms of HMGCR,and the application of inhibitors,as well as the role of HMGCR in liver diseases,in order to provide new insights for scientific research and the clinical prevention and treatment of liver diseases.