This study investigates the mechanism by which Xintong Granules improve myocardial ischemia-reperfusion injury(MIRI) through the regulation of gut microbiota and their metabolites, specifically short-chain fatty acids(SCFAs). Rats were randomly divided based on body weight into the sham operation group, model group, low-dose Xintong Granules group(1.43 g·kg~(-1)·d~(-1)), medium-dose Xintong Granules group(2.86 g·kg~(-1)·d~(-1)), high-dose Xintong Granules group(5.72 g·kg~(-1)·d~(-1)), and metoprolol group(10 mg·kg~(-1)·d~(-1)). After 14 days of pre-administration, the MIRI rat model was established by ligating the left anterior descending coronary artery. The myocardial infarction area was assessed using the 2,3,5-triphenyltetrazolium chloride(TTC) staining method. Apoptosis in tissue cells was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) assay. Pathological changes in myocardial cells and colonic tissue were observed using hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), creatine kinase MB isoenzyme(CK-MB), and cardiac troponin T(cTnT) in rat serum were quantitatively measured using enzyme-linked immunosorbent assay(ELISA) kits. The activities of lactate dehydrogenase(LDH), creatine kinase(CK), and superoxide dismutase(SOD) in myocardial tissue, as well as the level of malondialdehyde(MDA), were determined using colorimetric assays. Gut microbiota composition was analyzed by 16S rDNA sequencing, and fecal SCFAs were quantified using gas chromatography-mass spectrometry(GC-MS). The results show that Xintong Granules significantly reduced the myocardial infarction area, suppressed cardiomyocyte apoptosis, and decreased serum levels of pro-inflammatory cytokines(TNF-α, IL-1β, and IL-6), myocardial injury markers(CK-MB, cTnT, LDH, and CK), and oxidative stress marker MDA. Additionally, Xintong Granules significantly improved intestinal inflammation in MIRI rats, regulated gut microbiota composition and diversity, and increased the levels of SCFAs(acetate, propionate, isobutyrate, etc.). In summary, Xintong Granules effectively alleviate MIRI symptoms. This study preliminarily confirms that Xintong Granules exert their inhibitory effects on MIRI by regulating gut microbiota imbalance and increasing SCFA levels.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Myocardial Reperfusion Injury/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Apoptosis/drug effects* ; Humans ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/genetics* ; Malondialdehyde/metabolism*

OBJECTIVES: To investigate the relationship between the polygenic risks for various psychiatric disorders and clinical and neuropsychological characteristics in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Using a cross-sectional design, 285 children with ADHD and 107 healthy controls were assessed using the Child Behavior Checklist, the Behavior Rating Inventory of Executive Function for parents, the Wechsler Intelligence Scale for Children, Fourth Edition, and the Cambridge Neuropsychological Test Automated Battery. Blood samples were collected for genetic data. Polygenic risk scores (PRSs) for various psychiatric disorders were calculated using the PRSice-2 software. RESULTS: Compared with the healthy controls, the children with ADHD displayed significantly higher PRSs for ADHD, major depressive disorder, anxiety disorder, and obsessive-compulsive disorder (P<0.05). In terms of daily-life executive function, ADHD-related PRS was significantly correlated with the working memory factor; panic disorder-related PRS was significantly correlated with the initiation factor; bipolar disorder-related PRS was significantly correlated with the shift factor; schizophrenia-related PRS was significantly correlated with the inhibition, emotional control, initiation, working memory, planning, organization, and monitoring factors (P<0.05). The PRS related to anxiety disorders was negatively correlated with total IQ and processing speed index (P<0.05). The PRS related to obsessive-compulsive disorder was negatively correlated with the processing speed index and positively correlated with the stop-signal reaction time index of the stop-signal task (P<0.05). CONCLUSIONS PRSs for various psychiatric disorders are closely correlated with the behavioral and cognitive characteristics in children with ADHD, which provides more insights into the heterogeneity of ADHD.
Humans ; Attention Deficit Disorder with Hyperactivity/genetics* ; Child ; Male ; Female ; Cross-Sectional Studies ; Neuropsychological Tests ; Multifactorial Inheritance ; Adolescent ; Mental Disorders/etiology* ; Executive Function ; Genetic Risk Score

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective : To investigate the role of single nucleotide polymorphisms(SNP) of glutathione peroxidase 4(GPX4) gene in the risk of non-cardia gastric cancer. Methods: A total of 1 031 samples were selected, including 506 normal examiners and 525 patients with non-cardia gastric cancer.GPX4rs4807542, rs713041, rs2074451 and rs3746162 were genotyped by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Unconditional Logistic regression was used to analyze the relationship between each SNP with the risk of non-cardia gastric cancer under the four genetic models. Results : The CT+TT genotype of rs713041 reduced the risk of non-cardia gastric cancer compared with the CC genotype(OR=0.699, 95%CI: 0.537-0.910). The GT+TT genotype of rs2074451 reduced the risk of non-cardia gastric cancer compared with the GG genotype(OR=0.681,95%CI: 0.520-0.893). The G-C-G-C haplotype, constructed by the four SNPs ofGPX4, was related to an increased risk of non-cardia gastric cancer(OR=1.262, 95%CI: 1.035-1.539), and G-T-T-C haplotype was related to a decreased risk of non-cardia gastric cancer(OR=0.784, 95%CI: 0.656-0.937). The fourth-order interaction ofGPX4rs4807542, rs713041, rs2074451 and rs3746162 played a synergistic effect in the risk of non-cardia gastric cancer(P<0.05). Conclusion GPX4rs713041 and rs2074451 are related to non-cardia gastric cancer susceptibility. The G-C-G-C haplotype composed ofGPX4rs4807542, rs713041, rs2074451 and rs3746162 is a risk factor for non-cardia gastric cancer, while the G-T-T-C haplotype is a protective factor. The interaction betweenGPX4rs4807542, rs713041, rs2074451 and rs3746162 is closely connected with the occurrence of non-cardia gastric cancer.

Dopamine(DA)is an essential neurotransmitter.Research on its dynamic concentration fluctuations,particularly within the extracellular microenvironment,is crucial for elucidating neural signaling mechanisms and pathogenesis of related disorders.Among DA detection methods,fluorescence probe-based imaging offers advantages such as high sensitivity,high specificity,and non-invasiveness.However,the application of these probes for in situ DA monitoring has been limited by the challenges including probe internalization and difficulties in labeling across cells.Here,leveraging the programmability and high stability of DNA nanostructures,a DNA prism-based probe for imaging DA release at the single-cell level was designed and constructed.This probe utilized surface-modified cholesterol for efficient membrane anchoring and a DA aptamer-based"turn-on"sensing module to detect DA directly on the cell membrane.Using this probe,rapid DA release triggered by high K+stimulation was observed,with the released DA concentration increasing over time and peaking at 8 min post-stimulation.More notably,exploiting the probe's ability to simultaneously anchor to two cells,thereby forming cell clusters,revealed that the distribution of DA within the intercellular space was significantly higher than that in the cell body regions.This probe not only provided a method for DA imaging on the cell membrane but also laid a theoretical foundation for developing broader neurotransmitter detection platforms,holding significant scientific merit and application potential.

Objective To develop a predictive model for postoperative mortality risk in patients with acute aortic dissection(AAD)using the Extreme Gradient Boosting(XGBoost)algorithm combined with Shapley Additive Explanation(SHAP),and to establish a prediction website to serve as a diagnostic and therapeutic support platform for clinicians and patients.Methods A retrospective cohort study design was adopted.Data from 782 AAD patients who underwent surgical treatment at the Fourth Hospital of Hebei Medical University from January 2013 to December 2023 were collected,including basic information and initial serum biomarker test results.Patients were randomly divided into training and test sets at a 7:3 ratio.An external validation set consisting of 313 AAD patients admitted to the Second Hospital of Hebei Medical University from January 2020 to December 2023 was also established for further model validation.Variables were screened using LASSO regression,and an XGBoost machine learning model was constructed and interpreted using SHAP.The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curve analysis.Using the Shiny package,the XGBoost model was deployed to shinyapps.io to create a prediction website for postoperative mortality risk in AAD patients.One patient was selected by simple random sampling from the test set and the external validation set respectively for the prediction example on the Shiny webpage.Results The XGBoost model demonstrated high predictive performance for postoperative mortality in AAD patients,with area under the ROC curve(AUC)values of 0.928(95%CI 0.901-0.956)in the training set,0.919(95%CI 0.891-0.949)in the test set,and 0.941(95%CI 0.915-0.967)in the external validation set.SHAP values indicated the following order of variable importance in the model(from highest to lowest):"lactate dehydrogenase""blood chlorine""multiple organ injury""carbon dioxide combining power""prothrombin time""α-hydroxybutyric acid""creatine kinase isoenzyme""Stanford classification""combined use of bedside blood purification""gender""acute kidney injury""gastrointestinal bleeding""brain injury"and"shock".A risk prediction website for adverse postoperative outcomes in AAD patients was developed using XGBoost-SHAP method(https://dun-dunxiaolu.shinyapps.io/document/)and validated with examples.One randomly selected patient from each of the test and external validation sets was applied:the predicted mortality risk value for patient 1(who died postoperatively)was 0.9539,and that for patient 2(who survived postoperatively)was 0.0206.Conclusions The XGBoost-SHAP model demonstrates high accuracy in predicting postoperative mortality risk for AAD patients.The online prediction tool established based on this model enhances the identification efficiency of high-risk postoperative mortality patients.

Objective: To explore the association between mammalian sterile 20-like kinase 2(MST2) gene polymorphism and haplotype and the risk of colorectal cancer, rectal cancer, and colon cancer in the Han population in Baotou area by case-control association study. Methods: A total of 390 patients with colorectal cancer diagnosed by pathology and 413 normal physical examination pop-ulation were collected, and 2 mL of peripheral blood was taken for subsequent gene genotyping. Single nucleotide polymorphisms(SNPs) of MST2 gene were screened according to the genetic polymorphism data of Chinese Han population provided by the NCBI-Hapmap database. Gene genotyping was performed by Taqman method. Logistic regression was used to calculate the association between each SNP and the risk of colorectal cancer, colon cancer, and rectal cancer under codominant, dominant, overdominant, and recessive genetic models. Results: Five SNPs of MST2 gene were screened, namely rs11783149, rs10955176, rs7827435, rs4075986, rs3019295. Among them, SNP rs4075986 was associated with the risk of colorectal cancer. Compared with the rs4075986 GG+AA genotype, carrying the AG genotype [OR(95%CI)=2.473(1.844-3.316) could increase the risk of colorectal cancer. Compared with the rs4075986 GG genotype, carrying the AG+AA genotype [OR(95%CI)=2.475(1.844-3.323) could increase the risk of colorectal cancer. SNP rs4075986 and rs3019295 were associated with the risk of rectal cancer. Compared with the rs4075986 GG+AA genotype, carrying the AG genotype [OR(95%CI)=3.411(2.387-4.874)] could increase the risk of rectal cancer. Compared with the rs3019295 GG+AA genotype, carrying the AG genotype [OR(95%CI)=0.706(0.501-0.996)] could reduce the risk of rectal cancer. SNP rs11783149 and rs4075986 were associated with the risk of colon cancer. Compared with the rs11783149 CC genotype, carrying the TT [OR(95%CI)=10.883(1.186-99.862)] and CT [OR(95%CI)=1.665(1.036-2.675)] genotype could increase the risk of colon cancer, respectively. Compared with the rs4075986 GG genotype, the AG+AA genotype [OR(95%CI)=1.824(1.262-2.638)] could increase the risk of colon cancer. Conclusion MST2 gene SNP rs3019295 AG genotype may be protective factor for rectal cancer. SNP rs11783149 CT and TT genotypes maybe risk factors for colon cancer. SNP rs4075986 AG and AG+AA genotypes may be a common risk factors for colorectal cancer, rectal cancer and colon cancer.

Objective: To explore the association between single nucleotide polymorphism(SNP) in the arachidonate 15-lipoxygenase(ALOX15) gene and Helicobacter pylori(H. pylori) infection as well as the risk of non-cardia gastric cancer in Baotou Han population, and to provide experimental evidence and data support for the screening of susceptible population for non-cardia gastric cancer. Methods: A total of 458 cases with non-cardia gastric cancer and 460 healthy examination people were collected. The 14C urea breath test(UBT) and enzyme-linked immunosorbent assay(ELISA) were used to detect H. pylori infection in the 460 healthy individuals. The genotypes of ALOX15 rs2619112, rs2619118, rs2664593, rs7220870 were detected by polymerase chain reaction-restriction fragment length polymorphism, and the association of SNP with H. pylori infection as well as the risk of non-cardia gastric cancer was statistically analyzed. Results: The positive rate of H. pylori infection was 42.4%. ALOX15 rs2619112, rs2619118, rs2664593, and rs7220870 had no association with H. pylori infection. ALOX15 rs2619112, rs2664593, and rs7220870 were not associated with the risk of non-cardia gastric cancer. Compared with the carriers of(CC + CT) genotype, the carriers of rs2619118 TT genotype had an increased onset risk of non-cardia gastric cancer [OR(95%CI)=1.512(1.110-2.060)]. The haplotype ACCC constructed by ALOX15 rs2619112, rs2619118, rs2664593, and rs7220870 could reduce the onset risk of non-cardia gastric cancer. The second-order interaction of ALOX15 rs2619112 and rs2619118 was associated with the risk of non-cardia gastric cancer ( P < 0. 05 ) . Conclusion ALOX15 rs2619112 , rs2619118 , rs2664593 , rs7220870 may not play a major role in H. pylori infection. ALOX15 rs2619118 TT genotype is a risk factor for the development of non⁃cardia gastric cancer. The haplotype ACCC constructed by ALOX15 rs2619112 , rs2619118 , rs2664593 , and rs7220870 reduces the onset risk of non⁃cardia gastric cancer. The interaction of ALOX15 rs2619112 and rs2619118 has a synergistic effect in the development of non⁃cardia gastric cancer.

italic>Salvia apiana Jepson, commonly known as white sage, is a perennial sub-shrub of the Salvia genus in the Lamiaceae family with a long medicinal history. In this study, the complete chloroplast genome of S. apiana was sequenced using PacBio HiFi third-generation sequencing technology. The physical map of the genome was constructed, and the sequence structure features, codon preference, and repetitive sequences were analyzed. Furthermore, a comparative analysis of the chloroplast genome and phylogenetic evolution with closely related species within the same genus was conducted. The chloroplast genome of S. apiana was found to have a length of 151 701 bp (GenBank accession number: OR389048), with a typical quadripartite structure and a GC content of 38.06%. A total of 132 genes were annotated, including 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Among them, 17 genes contained introns, and 18 genes were present in duplicate copies. Codon preference analysis revealed a preference for codons ending with A or U. Analysis of repetitive structures in the S. apiana chloroplast genome identified 170 simple sequence repeat (SSR) sites and 65 scattered repeat sequences, with the majority of SSR sites composed of A and T. Phylogenetic analysis of the complete chloroplast genomes of 21 species within the same genus showed that S. apiana is most closely related to Salvia hispanica Ettling. ex Willk. & Lange, Salvia leucantha Cav., and Salvia tiliifolia Vahl. Comparative analysis of the chloroplast genomes revealed slight contraction and expansion of the inverted repeat (IR) boundaries in S. apiana, as well as multiple highly variable regions in the chloroplast genome sequence. This study establishes a method for de novo assembling the chloroplast genome of S. apiana using third-generation sequencing data and provides a comprehensive analysis of its chloroplast genome, which can serve as a theoretical basis for studies on chloroplast genetic engineering, genetic diversity analysis, molecular breeding, and species identification.

Objective To explore the association between mammalian sterile 20-like kinase 1(MST1)gene poly-morphism and haplotype and the risk of colorectal cancer,rectal cancer,and colon cancer in the Han population in Baotou area by case-control association study.Methods A total of 390 patients with colorectal cancer diagnosed by pathology and 413 normal physical examination population were collected,and 2 ml of peripheral blood was taken for subsequent gene genotyping.Single nucleotide polymorphisms(SNPs)of MST1 gene were screened according to the genetic polymorphism data of Chinese Han population provided by the National Center for Biotechnology In-formation-Haplotype Mapping database.Gene genotyping was performed by Taqman method.Logistic regression was used to calculate the association between each SNP and the risk of colorectal cancer,colon cancer,and rectal cancer under codominant,dominant,overdominant,and recessive genetic models.Results Four SNPs of MST1 gene were screened,namely rs8000,rs2234197,rs2267853,and rs6073629.Among them,SNP rs2234197 was associated with the risk of rectal cancer.Compared with the GG+AA genotype,the AG genotype could reduce the risk of rectal cancer,OR[95%confidence interval(CI)]=0.657(0.442-0.976).SNP rs8000 was associated with the risk of colon cancer.Compared with the TT+GT genotype,the GG genotype could reduce the risk of colon cancer[OR(95%CI)=0.425(0.182-0.992)].Conclusion MST1 gene SNP rs2234197 AG genotype and SNP rs8000 GG genotype may be protective factors for rectal cancer and colon cancer,respectively.