Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Objective To explore the analytical methods combining multicolor flow cytometry with bioinformatics techniques for analyzing myeloid cells in the gastrocnemius of mice after muscle injury, and provide an experimental foundation for the study of muscle regeneration mechanisms. Methods Immune cells were collected from single-cell suspensions of mouse gastrocnemius using multicolor flow cytometry, and data were analyzed by the t-distributed stochastic neighbor embedding（t-SNE）algorithm supplemented by manual gating techniques. The tSNE algorithm was used in multicolor flow cytometry to guide the setting of manual gates, optimize the identification and classification of cell populations. Results Compared to the sham surgery group, the proportions of dendritic cells, granulocytes, macrophages, and monocytes at the site of muscle injury in the model group significantly increased, with the increasing in monocytes being particularly notable. Conclusion The application of the tSNE algorithm combined with manual gating techniques in multicolor flow cytometry demonstrated that this method could effectively guide the setting of manual gates and enhance the efficiency of distinguishing immune cell types. Through this combined technology, the function and subtypes of myeloid cells in the mouse gastrocnemius could be analyzed more accurately.

Objective: To investigate the attention cognitive function and symptom correlations of school aged children with attention deficit hyperactivity disorder (ADHD)using event related potential (ERP) technology, so as to provide references for the early diagnosis of children with ADHD. Methods: A total of 52 school aged children diagnosed with ADHD at the outpatient department of the Third Affiliated Hospital of Zhengzhou University from September 2022 to September 2024 and 50 age /sex matched healthy controls were selected. The ERP experiment adopted the auditory Oddball task to conduct comparative analyses of the amplitude and latency of the mismatch negative(MMN) at the Fz, Cz, and Pz points of the scalp electrode and the P3a component respectively. The symptom assessment scales adopted the Swanson,Nolan,and Pelham-Ⅳ Rating Scale (SNAP-Ⅳ) and the Parent Symptom Questionnaire (PSQ), which were filled out by the parents. Spearman correlation analysis was used to analyze the correlation between ERP components and symptoms in schoolaged children with ADHD. Results: The latency of MMN components in the healthy control group on the Fz lead was (188.30±2.06)ms, and the amplitude was (-15.54±1.35)μV; the latency of the P3a component on the Pz lead was (312.82±7.80)ms, and the amplitude was (3.80±0.18)μV. The latency of MMN components in the ADHD group on the Fz lead was (188.94±1.39)ms, and the amplitude was (-14.78±1.40)μV; the latency of the P3a component on the Pz lead was (317.21±5.65)ms, and the amplitude was (3.70±0.13)μV. Compared with normal children, the MMN of children with ADHD had smaller amplitudes in the Fz and Cz leads, and the P3a had greater latency and smaller amplitudes in the Cz and Pz leads ( t =2.79,2.20；-2.04，-3.25；2.35,3.21， P <0.05). Correlation analysis showed that the latency of MMN in children with ADHD was positively correlated with the inattention score in the SNAP-Ⅳ( r =0.22), and the amplitude of MMN was negatively correlated with the inattention score in the SNAP-Ⅳ and the learning problem score in PSQ ( r = -0.26 , -0.34)( P <0.05). The latency of P3a was positively correlated with the scores of inattention in the SNAP-Ⅳ and the score of learning problems in the PSQ ( r =0.26 ,0.24); the amplitude of P3a was negatively correlated with the scores of attention deficit and hyperactivity/impulsivity in the SNAP-Ⅳ and the scores of learning problems and impulsivity/hyperactivity in the PSQ( r = -0.26 , -0.22, -0.25,-0.32)( P <0.05). Conclusions School aged ADHD children exhibit abnormal MMN/P3a components, indicating attention related cognitive dysfunction. Symptoms such as inattention, learning problems and hyperactivity/impulsivity in children with ADHD are related to abnormal components of MMN and P3a.

Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most prevalent chronic liver disease globally,encompassing the entire spectrum of fatty liver pathogenesis.It progresses from simple steatosis to metabolic-associated steatohepatitis(MASH),involving injury and inflammation,with or without fibrosis,ultimately leading to cirrhosis and hepatocellular carcinoma,which affects approximately a quarter of the world's population.Liver biopsy remains the gold standard for differentiating MASH from steatosis and assessing advanced fibrosis.However,its limitations,including costliness,invasiveness,and sampling bias,have spurred the development of noninvasive diagnostic techniques.In addition,there are no FDA-approved drugs for the treatment of MASLD.Enumerating noninvasive diagnostic markers that have the potential to replace liver biopsy were summarized,and the current treatment options for MASLD were discussed,with clinical trials designed to evaluate the efficacy and safety of single agents or combination therapies to halt or reverse disease progression,which could provide new insights for the clinical diagnosis and treatment of MASLD.

Objective This study aimed to identify PAX9 variants in non-syndromic tooth agenesis families of Chi-na,as well as to analyze the genotype-phenotype of non-syndromic tooth agenesis caused by PAX9 variants,which can provide a basis for the genetic diagnosis of tooth agenesis.Methods We collected the data of 44 patients with non-syn-dromic oligodontia who underwent treatment at Stomatological Hospital of Hebei Medical University between 2018 and 2023.Whole-exome sequencing was performed on the peripheral blood of the proband and its core family members,and the variants were verified by Sanger sequencing.Pathogenicity analysis and function prediction of the variants were per-formed using bioinformatics tools.The correlation between the genotype of PAX9 variant and its corresponding pheno-type was examined by reviewing 55 publications retrieved from PubMed.The studies involved 232 tooth agenesis pa-tients with PAX9 variants.Results A novel PAX9 c.447delG(p.Pro150Argfs*62)and a reported PAX9 c.406C>T(p.Gln136*)were identified in two Chinese families.Through bioinformatics analysis and three-dimensional structural mod-eling,we postulated that the frameshift variant was pathogenic.The outcome was the premature cessation of PAX9 pro-tein,which caused severe structural and functional deficiencies.Summarizing the PAX9 genotype-phenotype relationship revealed that patients carrying the PAX9 variant commonly led to loss of the second molars.Conclusion We identified the novel PAX9 c.447delG(p.Pro150Argfs*62)in a Chinese family of non-syndromic oligodontia,expanding the known variant spectrum of PAX9.The most susceptible tooth position for PAX9 variants of tooth agenesis was the second mo-lars and the deciduous molars during the deciduous dentition.

[Objective]To enrich the modern scientific connotation of the theory"spleen being in charge of the defensive function"in traditional Chinese medicine,and provide ideas for experimental research and clinical treatment of ulcerative colitis(UC).[Methods]Starting from the congruency between the therapeutic principle and method for UC in traditional Chinese medicine and the theory"spleen being in charge of the defensive function",and taking into account the fact that various components of Huangya Decoction were scientifically proven to effectively alleviate UC symptoms,this article discussed the potential mechanism of classic formula of Huangya Decoction in treating UC via"strengthening the spleen and enriching Qi"by explaining the theoretical connotation and immunological extension of"spleen being in charge of the defensive function",and combining with modern pharmacological research.[Results]Although studies on the treatment of UC by Huangya Decoction are still lacking,Huangya Decoction is feasible to treat UC by strengthening the spleen and enriching Qi based on the theory"spleen being in charge of the defensive function"in traditional Chinese medicine.The potential mechanisms include regulating immune cells,protecting intestinal epithelial barrier function,regulating intestinal flora,inhibiting or alleviating inflammatory response and regulating autophagy pathway expression.[Conclusion]The theoretical connotation of"spleen being in charge of the defensive function"in traditional Chinese medicine exhibits homologous physiological effects with the immune function in modern medicine,resulting from the synergistic action of multiple organs such as the spleen and gastrointestinal tract.The application of Huangya Decoction,a classic formula of strengthening the spleen and enriching Qi,for the treatment of UC through multi-target and multi-link approaches is not only feasible but also provides new insights for UC therapy.It lays a foundation for the systematic research,development and utilization of basic theories in traditional Chinese medicine and classic formulas.

[Objective]To investigate the therapeutic effect of Jian'gan Xiaozhi Decoction(JGXZ)on non-alcoholic fatty liver disease(NAFLD)model mice and explore its mechanism from the perspective of mitochondrial autophagy mediated by the PTEN induced putative kinase 1(PINK1)/E3 uniquitin-protein ligase(Parkin)signaling pathway.[Methods]Sixty C57BL/6J mice were randomly and equally divided into 6 groups:control,model(NAFLD),polyene phosphatidyl choline(PPC)group 180 mg/kg intragastric administration,and JGXZ low,medium and high dose groups(8,16,32 g/kg)intragastric administration.Except for control group,the other 5 groups were given a high fat diet.The treatment lasted for 8 weeks,and the body weight of the mice was recorded weekly.After 8 weeks,blood samples were collected,the levels of serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were measured,liver tissue was weighted and fixed,and histological changes in liver tissue were observed by hematoxylin-eosin(HE)and oil red O staining.The levels of total cholesterol(TC),triglyceride(TG),interleukin-1 β(IL-1 β),IL-6,tumor necrosis factor-α(TNF-α),malondialdehyde(MDA)and activities of glutathione peroxidase(GSH-Px),superoxide dismutase(SOD)in liver tissue were measured to evaluate the effects of JGXZ on inflammation and oxidative stress in NAFLD mice.Western blot was used to detect the protein expression levels of voltage-dependent anion channel 1(VDAC1),translocase of outer mitochondrial membrane 20(TOM20),cytochrome c oxidase subunit Ⅳ(COX Ⅳ),phosphatase and PINK1,Parkin,Beclin1,microtubule-associated protein light chain 3(LC3),and P62 to evaluate the effects of JGXZ on mitochondrial autophagy in NAFLD mice.[Result]Compared with model group,JGXZ intervention significantly improved the body weight of NAFLD model mice,reduced liver index,alleviated liver tissue lesions in NAFLD model mice,reduced TC,TG,ALT,AST levels,decreased IL-1[3,IL-6,TNF-α and MDA levels,increased GSH-Px and SOD activity,down-regulated VDAC1,TOM20,COXⅣ and P62 protein expression,and up-regulated PINK1,Parkin,Beclin1,LC3 protein expression.[Conclusion]JGXZ can alleviate liver injury in NAFLD mice by promoting the PINK 1/Parkin signaling pathway mediated activation of mitochondrial autophagy.

[Objective]To analyze the medication rules and mechanism in treatment of children with functional constipation(FC)by activating the spleen.[Methods]Collecting 562 cases of children with functional constipation,cluster analysis was conducted using SPSS Statistics 24.0 software,association rule analysis was performed using SPSS Modeler 18.0 software,and complex network analysis was carried out using Liquorice software to derive the core formula.The active ingredients and targets of the core formula were screened using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM),the targets related to FC were screened by Genome Annotation Database Platform(GeneCards),and the predicted targets were obtained after taking the intersection.Based on the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)database,the target gene protein-protein interaction(PPI)network was constructed,Cytoscape 3.8.0 software was used to build the core formula component-constipation-target network map,and topology analysis was performed with the help of Network Analyzer tool to identify the core targets.Based on the STRING database,gene ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed by using R language 4.2.2.[Results]The cases contained 1 121 prescriptions.The improvement rate of symptoms in each course was 86％to 97％,and the improvement rate of the three main symptoms of constipation was around 90％.Drug properties were mainly cold and flat,mostly were bitter and sweet.The drugs commonly belonged to the stomach and spleen.The core formula was obtained by drug association,clustering and complex network analysis,and was composed of nine drugs.The main active ingredients of the core formula were quercetin,methylheptenone,bile triene,niacin,lignan,kaempferol and baicalin.The key targets included prostaglandin-endoperoxide synthase 2(PTGS2),V-Jun sarcoma virus 17 oncogene homolog(JUN),protein kinase B1(AKT1),phosphoinositide-3-kinase regulatory subunit 1(PIK3R1),phosphatidylinositol-4,5-bisphosphate-3-kinase catalytic subunit alpha isoform(PIK3CA),and the regulation of inflammation-related pathways such as phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)may be the mechanism of action of the core formula relieving constipation.[Conclusion]The core formula for the treatment of pediatric constipation by activating-spleen includes Zhishi(Aurantii Fructus Immaturus),Houpo(Magnoliae Officinalis Cortex),Baizhu(Atractylodis Macrocephalae Rhizoma),Jineijin(Galli Gigerii Endothelium Corneum),Shanzha(Crataegi Fructus),Lianqiao(Forsythiae Fructus),Juemingzi(Cassiae Semen),Huomaren(Cannabis Fructus),Huhuanglian(Picrorhizae Rhizoma),whose main components may affect the level of inflammatory factors and repairing the intestinal mucosa to restore the function of the intestinal smooth muscle,which has certain implications for the clinical application of the method of activating the spleen and the Chinese medicine treatment of FC in children.