Objective To investigate the influencing factors for hemorrhagic transformation （HT） after intravenous thrombolysis （IVT） in patients with acute ischemic stroke （AIS） in plateau areas. Methods A retrospective analysis was performed for AIS patients who were admitted to our hospital from February 2019 to April 2024 and received IVT with urokinase or recombinant tissue plasminogen activator， and according to the presence or absence of HT after IVT， they were divided into HT group and non-HT group. The multivariate Logistic regression analysis was used to investigate the independent risk factors for HT after IVT in AIS patients. Results A total of 437 AIS patients who underwent IVT were included in this study， among whom 45 （10.3%） experienced HT. There were significant differences between the HT group and the non-HT group in the proportion of patients with a past history of atrial fibrillation， systolic blood pressure on admission， NIHSS score before thrombolysis， neutrophil-to-lymphocyte ratio （NLR）， and blood glucose before thrombolysis （all P<0.05）. The above factors were included in a multivariate logistic regression model， and the results showed that blood glucose on admission（OR=1.122，95%CI 1.007~1.251，P<0.05） and history of atrial fibrillation （OR=3.896，95%CI 1.632~9.303，P<0.05）were independent risk factors for HT after IVT. Conclusion History of atrial fibrillation， systolic blood pressure on admission， NIHSS score before thrombolysis， blood glucose level on admission， and NLR level before treatment are influencing factors for HT after IVT in AIS patients in plateau areas， among which history of atrial fibrillation and blood glucose level before thrombolysis are independent risk factors.

ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

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.

ObjectiveTobacco-related diseases remain one of the leading preventable public health challenges worldwide and are among the primary causes of premature death. In recent years, accumulating evidence has supported the classification of nicotine addiction as a chronic brain disease, profoundly affecting both brain structure and function. Despite the urgency, effective diagnostic methods for smoking addiction remain lacking, posing significant challenges for early intervention and treatment. To address this issue and gain deeper insights into the neural mechanisms underlying nicotine dependence, this study proposes a novel graph neural network framework, termed TI-GNN. This model leverages functional magnetic resonance imaging (fMRI) data to identify complex and subtle abnormalities in brain connectivity patterns associated with smoking addiction. MethodsThe study utilizes fMRI data to construct functional connectivity matrices that represent interaction patterns among brain regions. These matrices are interpreted as graphs, where brain regions are nodes and the strength of functional connectivity between them serves as edges. The proposed TI-GNN model integrates a Transformer module to effectively capture global interactions across the entire brain network, enabling a comprehensive understanding of high-level connectivity patterns. Additionally, a spatial attention mechanism is employed to selectively focus on informative inter-regional connections while filtering out irrelevant or noisy features. This design enhances the model’s ability to learn meaningful neural representations crucial for classification tasks. A key innovation of TI-GNN lies in its built-in causal interpretation module, which aims to infer directional and potentially causal relationships among brain regions. This not only improves predictive performance but also enhances model interpretability—an essential attribute for clinical applications. The identification of causal links provides valuable insights into the neuropathological basis of addiction and contributes to the development of biologically plausible and trustworthy diagnostic tools. ResultsExperimental results demonstrate that the TI-GNN model achieves superior classification performance on the smoking addiction dataset, outperforming several state-of-the-art baseline models. Specifically, TI-GNN attains an accuracy of 0.91, an F1-score of 0.91, and a Matthews correlation coefficient (MCC) of 0.83, indicating strong robustness and reliability. Beyond performance metrics, TI-GNN identifies critical abnormal connectivity patterns in several brain regions implicated in addiction. Notably, it highlights dysregulations in the amygdala and the anterior cingulate cortex, consistent with prior clinical and neuroimaging findings. These regions are well known for their roles in emotional regulation, reward processing, and impulse control—functions that are frequently disrupted in nicotine dependence. ConclusionThe TI-GNN framework offers a powerful and interpretable tool for the objective diagnosis of smoking addiction. By integrating advanced graph learning techniques with causal inference capabilities, the model not only achieves high diagnostic accuracy but also elucidates the neurobiological underpinnings of addiction. The identification of specific abnormal brain networks and their causal interactions deepens our understanding of addiction pathophysiology and lays the groundwork for developing targeted intervention strategies and personalized treatment approaches in the future.

Objective: To understand the incidence risk and risk factors of tuberculosis (TB) among middle school students in Chongqing, so as to provide a basis for formulating TB prevention and control strategies. Methods: From September to December 2022, 32 181 middle school students were selected as the study cohort from 15 administrative districts in Chongqing by using the stratified cluster random sampling method. All cohort members were screened with the tuberculin skin test (TST), and relevant information was collected from January 1, 2023 to December 31, 2024. On the basis of active screening, the follow up data of the participants were compared with the National Tuberculosis Management Information System to obtain the incidence status of the study subjects. The Log rank test was used to compare the TB incidence rates among students with different characteristics, and a Cox proportional hazards model was established to analyze the incidence risk and risk factors of TB. Results: The TST screening rate of the cohort members was 93.0%. During the 2 year follow up period, a total of 36 TB cases occurred, with a cumulative incidence rate of 111.87/100 000 and an incidence density of 55.95/100 000. Among them, the cumulative incidence rate of students from public schools (170.44/ 100 000 ) was higher than that of students from private schools (41.16/100 000), the cumulative incidence rate of students in schools located in high epidemic areas (153.95/100 000) was higher than that in medium epidemic areas (69.00/100 000), and the difference was statistically significant ( χ 2=11.49, 4.73, both P <0.05). The Log-rank test for different TST results showed that the difference in TB comulative incidence rate between students with strongly positive TST results (216.55/ 100 000 ) and those with negative TST results (81.40/100 000) was statistically significant ( χ 2=5.85, P <0.05). Univariate analysis using the Cox proportional hazards model revealed that the risk of TB was lower in students from private schools ( HR=0.25, 95% CI = 0.10-0.59) and students in medium epidemic areas ( HR=0.46, 95%CI =0.23-0.94); whereas the risk of TB was increased in students with strongly positive TST results ( HR=1.39, 95%CI =1.05-1.84) (all P <0.05). Multivariate Cox regression analysis showed that the risk of TB in students from private schools was lower than that of students from public schools ( HR=0.23, 95%CI=0.08-0.62, P <0.05). Conclusions The annual average incidence rate of TB among middle school students in Chongqing is at a relatively high level. It is necessary to strengthen the management and intervention for student groups, including those in public schools, those in schools located in high epidemic areas, and those with strongly positive TST results, so as to reduce the incidence rate of TB.

BACKGROUND: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

Alzheimer's disease (AD) is the commonest neurodegenerative disease that causes memory decline, cognitive dysfunction and behavior disorders in the aged people. Primary pathological hallmarks of AD include amyloid-β (Aβ), neurofibrillary tangles (NFTs), gliosis, and neuronal loss. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have important physiological functions, especially in aspects of controlling the resting membrane potential, pacemaker activity, memory formation, sleep and arousal. This article reviews the structure, distribution, regulation of HCN channels and the role of HCN channels in the pathological mechanisms of AD, aiming to provide drug therapeutic targets for the prevention and treatment of AD.
Humans ; Alzheimer Disease/physiopathology* ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/physiology* ; Animals ; Amyloid beta-Peptides/metabolism*

Salvia miltiorrhiza is a perennial herb of the genus Salvia(Lamiaceae). As one of the earliest medicinal plants to undergo molecular biology research, it has gradually become a model plant for molecular biology of medicinal plants. With the gradual analysis of the genome of S. miltiorrhiza and the biosynthetic pathways of its main active components tanshinone and salvianolic acids, the transcriptional regulation mediated by transcription factors and related regulatory proteins has gradually become a new research focus. Due to the lack of scientific and unified naming of transcription factors and different research indexes in different literature, this paper systematically sorted out the transcription factors in different literature with the genomes of DSS3 from selfing for three generations and bh2-7 from selfing for six generations as reference. In total, 73 transcription factors and related regulatory proteins belonging to 13 gene families were identified. The effects of overexpression or gene silencing experiments on tanshinone and salvianolic acids were also analyzed. This study unified the identified transcription factors, which laid a foundation for further constructing the regulatory networks of secondary metabolites and insect or stress resistance and improving the quality of medicinal materials by using global transcriptional regulation engineering.
Salvia miltiorrhiza/chemistry* ; Plant Proteins/metabolism* ; Gene Expression Regulation, Plant ; Transcription Factors/metabolism* ; Abietanes/metabolism*