ObjectiveTo investigate the mechanism of Xiezhuo Jiedu prescription in the treatment of ulcerative colitis （UC） by inhibiting ferroptosis and alleviating intestinal mucosal injury based on the nuclear factor E₂ related factor 2/solute carrier family 7 member/glutathione peroxidase 4 （Nrf2/SLC7A11/GPX4） signaling pathway. MethodsA total of 60 male SD rats were divided into a normal group， a model group， high- and low-dose Xiezhuo Jiedu prescription groups （26.64 and 13.32 g·kg^-1， respectively）， a ferroptosis inhibitor group （Ferrostatin-1， 0.005 g·kg^-1）， and a mesalazine group （0.27 g·kg^-1）， with 10 rats in each group. A UC rat model was established by intrarectal administration of trinitrobenzene sulfonic acid （TNBS）-ethanol. The normal group and the model group were intragastrically administered normal saline. The other groups were given intragastric administration according to the corresponding dosage for 7 d. The general condition， disease activity index （DAI） score， colon length， and mucosal injury index （CDMI） score were observed in each group. The pathological changes of colon tissue in each group were observed by hematoxylin-eosin （HE） staining. The intestinal mucosa and mitochondrial morphology in each group were observed by transmission electron microscopy. The expression levels of Occludin， Claudin-1， mucin 2 （MUC2）， and E-cadherin in intestinal tissue were detected by immunofluorescence （IF）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of serum tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in each group， and a lactic acid assay kit or ELISA was employed to detect the expression levels of reactive oxygen species （ROS）， ferrous ions （Fe²⁺）， glutathione （GSH）， malondialdehyde （MDA）， 4-hydroxynonenal （4-HNE）， diamine oxidase （DAO）， and D-lactate （D-LA）. Real-time quantitative polymerase chain reaction （Real-time PCR） was applied to detect the mRNA expression levels of Nrf2， SLC7A11， GPX4， Occludin， Claudin-1， MUC2， and E-cadherin in each group， and Western blot was adopted to detect the protein expression levels of Nrf2， p-Nrf2， SLC7A11， and GPX4 in each group. ResultsCompared with the normal group， rats in the model group exhibited listlessness， sluggish response， and mucopurulent and bloody stools. The model group also showed significantly increased DAI score， colon length， CDMI score， and expression levels of TNF-α， IL-6， ROS， Fe²⁺， MDA， 4-HNE， DAO， and D-LA （P<0.01）. In addition， it presented significantly decreased IF values of Occludin， Claudin-1， MUC2， and E-cadherin and mRNA and protein expression levels of IL-10， GSH， Nrf2， p-Nrf2， SLC7A11， and GPX4 （P<0.01）. There were different degrees of improvement in each administration group after treatment， and the improvement was the most significant in the high-dose Xiezhuo Jiedu prescription group （P<0.01）. ConclusionXiezhuo Jiedu prescription may alleviate intestinal mucosal injury by inhibiting ferroptosis of intestinal epithelial cells via regulating the Nrf2/SLC7A11/GPX4 signaling pathway， thereby exhibiting efficacy in the treatment of UC.

OBJECTIVE To study the mechanism of Xinnao shutong capsule alleviating cerebral ischemia reperfusion injury （CIRI） in rats by regulating the ferroptosis pathway. METHODS SD rats were randomly divided into sham operation group， model group， Xinnao shutong low-dose， high-dose group （220， 440 mg/kg）， Ginkgo biloba leaves extract group （positive control， 150 mg/kg）. Each group of rats was orally administered with the corresponding medication/normal saline for 7 consecutive days. Transient occlusion of the middle cerebral artery was adopted to induce the CIRI model； the samples were taken 24 h after the operation； the cerebral infarction area of rats was detected， and the cerebral infarction rate was calculated. The pathological changes of brain tissues were observed， and the levels of lipid peroxide （LPO）， malondialdehyde （MDA） and glutathione （GSH） in cerebral tissue were detected； mRNA and protein expressions of nuclear factor-erythroid 2-related factor 2 （Nrf2）， heme oxygenase 1（HO-1） and glutathione peroxidase 4 （GPX4） were all detected in cerebral tissue of rats. RESULTS Compared with model group， the cerebral infarction rate， the content of total iron in cerebral tissue and serum level of LPO （except for Ginkgo biloba leaves extract group and Xinnao shutong low-dose group） were all decreased significantly in G. biloba leaves extract group and Xinnao shutong groups （P＜0.05 or P＜0.01）； the serum level of GSH， the protein and mRNA expressions of Nrf2， HO-1 and GPX4 were all increased significantly （P＜0.05 or P＜0.01）. The pathological damage to brain tissue was reduced， the number of nerve cells increased， the edema was alleviated， and the nuclear membrane was flattened. CONCLUSIONS Xinnao shutong capsule can inhibit ferroptosis and reduce CIRI， the mechanism of which may be associated with the activation of the Nrf2/HO-1/GPX4 signaling pathway.

ObjectiveThis study aims to explore the potential mechanism of the Xiezhuo Jiedu formula in regulating pyroptosis for the treatment of ulcerative colitis （UC） using bioinformatics and in vivo animal experiments. MethodsDifferentially expressed genes （DEGs） in colon tissues of UC patients were retrieved from the Gene Expression Omnibus （GEO） database. Pyroptosis-related genes were obtained from the GEO and GeneCards databases. The intersection of these datasets yielded pyroptosis-related DEGs （Pyro-DEGs）. Pyro-DEGs were subjected to Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis using the Metascape database. A protein-protein interaction （PPI） network was constructed using the STRING database. Least absolute shrinkage and selection operator （LASSO） prediction model and receiver operating characteristic （ROC） analysis were conducted to identify core Pyro-DEGs with diagnostic and therapeutic potential. Immune infiltration analysis of the UC datasets was performed using the deconvolution method （CIBERSORT）， along with correlation analysis with core Pyro-DEGs. Sixty male Sprague-Dawley （SD） rats were randomly divided into a control group， a model group， high-， medium-， and low-dose groups of Xiezhuo Jiedu formula （26.64， 13.32， 6.66 g·kg^-1）， and a mesalazine group （0.27 g·kg^-1）， with 10 rats in each group. UC was established by intrarectal administration of 3，5-trinitrobenzenesulfonic acid （TNBS） dissolved in ethanol. The control and model groups were given distilled water by gavage， while the treatment groups were administered the corresponding drugs for 7 consecutive days. Hematoxylin-eosin （HE） staining was used to observe the colon histopathology. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of inflammatory factors such as interleukin-1β （IL-1β）， IL-10， IL-18， and transforming growth factor-β （TGF-β）. Immunohistochemistry （IHC） and Western blot were applied to detect the expression of Caspase-1， gap junction alpha-1 protein （GJA1）， peroxisome proliferator-activated receptor gamma （PPARG）， and S100 calcium-binding protein A8 （S100A8）. Real-time quantitative polymerase chain reaction （Real-time PCR） was utilized to measure mRNA expression of Caspase-1， GJA1， PPARG， and S100A8. Western blot was performed to assess protein expression levels of Caspase-1， GJA1， PPARG， and S100A8. ResultsGEO datasets GSE87466 and GSE87473 yielded 64 Pyro-DEGs. KEGG analysis indicated that these genes were enriched in the NOD-like receptor signaling pathway， tumor necrosis factor （TNF） signaling pathway， and hypoxia-inducible factor 1 （HIF-1） signaling pathway. Four core Pyro-DEGs （Caspase-1， GJA1， PPARG， and S100A8） were identified. Immune infiltration analysis showed that expression of these genes was positively correlated with mast cells， neutrophils， M0 macrophages， M1 macrophages， and dendritic cells. Animal experimental results indicated that compared with the control group， the model group had significantly increased levels of IL-1β and IL-18， significantly decreased levels of IL-10 and TGF-β. The model group showed enhanced Caspase-1， GJA1， and S100A8 staining， and significantly increased mRNA and protein expression of Caspase-1， GJA1， and S100A8 （P<0.01）. In contrast， the expression of PPARG was reduced in the model group （P<0.01）. After treatment， all dosage groups showed varying degrees of improvement （P<0.05， P<0.01）， with the high-dose group showing the most significant improvement （P<0.01）. ConclusionCaspase-1， GJA1， PPARG， and S100A8 are core Pyro-DEGs closely associated with the pathogenesis of UC. These genes may collaborate with immune cells such as mast cells， neutrophils， and M0 macrophages to mediate disease development. The Xiezhuo Jiedu formula may regulate the expression of core Pyro-DEGs through the NOD-like receptor， TNF， and HIF-1 core signaling pathways， thereby modulating immune homeostasis in UC rats and effectively alleviating UC.

ObjectiveTo investigate the relationship between mitochondrial DNA copy number (mtDNAcn) and cognitive dysfunction, and its mediating role between type 2 diabetes mellitus (T2DM) and cognitive dysfunction. MethodsA case-control study was conducted from May 2019 to April 2021 at the Shanghai Yangpu District Central Hospital, China. A total of 193 subjects were recruited and divided into two groups based on the Montreal Cognitive Assessment (MoCA): normal control (NC) group (n=95) and cognitive impairment group (n=98). The prevalence of T2DM was determined on the basis of medical history, while mtDNAcn in peripheral blood samples was quantified using realtime fluorescent quantitative polymerase chain reaction. ResultsUnivariate analyses revealed that the mean mtDNAcn in the cognitive impairment group was 0.76±0.37, significantly lower than that in the NC group (1.06±0.45) (P<0.05). Logistic regression analyses showed that higher mtDNAcn was associated with a reduced risk of cognitive impairment (OR=0.315, 95%CI: 0.125‒0.795). Additionaly, a statistically significant positive correlation was observed between mtDNAcn and the total MoCA score (r=0.381, P<0.01). Morever, T2DM history (OR=2.741, 95%CI: 1.002‒7.497) and elevated glycosylated hemoglobin (HbA1c) levels (OR=1.796, 95%CI: 1.190‒2.711) were identified as risk factors for cognitive impairment. Mediation analyses indicated that mtDNAcn served as a mediator between T2DM/HbA1c and the risk of cognitive impairment, with proportions of mediating effect of 9.04% and 9.18%, respectively. ConclusionPatients with mild and moderate cognitive impairment have significantly lower mtDNAcn than those with normal cognitive function. Reduced mtDNAcn is an influencing factor for cognitive dysfunction and may play a mediating role in the association between T2DM and mild to moderate cognitive impairment.

Objective: To investigate the influencing factors for cognitive function among aluminum workers, so as to provide the basis for intervention and prevention of cognitive function among aluminum-exposed populations. Methods: From July to August 2019, male aluminum workers in the electrolytic aluminum workshop of an aluminum factory in Shanxi Province were selected using the cluster sampling method. Demographic information, prevalence of chronic diseases, lifestyle behaviors, night shifts, and sleep quality were collected through questionnaire surveys. Blood aluminum levels were measured using inductively coupled plasma-mass spectrometry. Cognitive function was investigated using the Montreal Cognitive Assessment. Factors affecting cognitive function among aluminum workers were analyzed by a quantile regression model. Results: A total of 142 aluminum workers were surveyed, including 57 workers aged 20 to <40 years (40.14%) and 85 workers aged 40 to 60 years (59.86%). The median blood aluminum level was 38.23 (interquartile range, 21.82) μg/L. The median cognitive function score was 24.00 (interquartile range, 3.00) points. Quantile regression analysis revealed that older age (βQ5=-0.186, 95%CI: -0.269 to -0.102), lower educational level (βQ5=1.933, 95%CI: 1.029 to 2.838; βQ10=1.743, 95%CI: 0.480 to 3.006; βQ50=1.038, 95%CI: 0.141 to 1.935; βQ75=1.006, 95%CI: 0.437 to 1.575; βQ90=1.111, 95%CI: 0.291 to 1.930), smoking (βQ5=-2.056, 95%CI: -3.264 to -0.849), alcohol consumption (βQ5=-1.821, 95%CI: -3.247 to -0.396) and higher blood aluminum level (βQ5=-0.075, 95%CI: -0.110 to -0.040; βQ10=-0.078, 95%CI: -0.127 to -0.029; βQ50=-0.075, 95%CI: -0.110 to -0.040; βQ75=-0.057, 95%CI: -0.079 to -0.035; βQ90=-0.067, 95%CI: -0.099 to -0.035) were associated with cognitive function decline among aluminum workers. Conclusions Educational level and blood aluminum level are the main factors affecting the cognitive function among aluminum workers. Among those with lower cognitive function scores, age, smoking and alcohol consumption are also associated with cognitive function.

OBJECTIVE To provide practical basis and policy recommendations for improving the pharmacovigilance （PV） system construction in medical institutions across China. METHODS A questionnaire survey was conducted using a mixed sampling strategy of “online random sampling+offline supplementary sampling” to distribute questionnaires among pharmaceutical professionals in tertiary medical institutions nationwide. The questionnaire covered aspects such as the construction of PV systems， job position settings， information system support， operational practices， and multi-stakeholder collaboration. The data were analyzed using descriptive methods and SPSS 20.0 statistical software. RESULTS A total of 70 valid questionnaires were collected from 66 medical institutions， primarily Class A tertiary hospitals. The survey found that 90.00% had designated PV personnel and 74.29% routinely conducted PV activities. However， there were notable disparities in resource allocation and information system capacity， with less than 50% of the institutions conducting post-marketing drug re-evaluation. PV activities were primarily focused on the collection and reporting of adverse drug reactions， with limited capabilities in signal detection and risk assessment. CONCLUSIONS Among the surveyed tertiary hospitals， PV systems have begun to take shape. However， challenges persist in terms of system establishment， resource allocation， risk assessment， and inter-organizational coordination. Policy efforts should focus on strengthening regulatory frameworks， improving information sharing mechanisms， enhancing professional training， and strengthening collaboration between hospitals and market authorization holders to ensure the effective implementation of PV in medical institutions.

Ischemic stroke is the leading cause of disability and mortality worldwide. The blood‒brain barrier (BBB) is the first line of defense after ischemic stroke. Disruption of the BBB induced by brain microvascular endothelial cells (BMECs) dysfunction is a key event that triggers secondary damage to the central nervous system, where blood-borne fluids and immune cells penetrate the brain parenchyma, causing cerebral edema and inflammatory response and further aggravating brain damage. Here, we develop a novel artificial mesenchymal stem cell (MSC) extracellular vesicles by integrating MSC membrane proteins into liposomal bilayers, which encapsulated miR-132-3p with protective effects on BMECs. The artificial extracellular vesicles (MSCo/miR-132-3p) had low immunogenicity to reduce non-specific clearance by the mononuclear phagocytosis system (MPS) and could target ischemia-injured BMECs. After internalization into the damaged BMECs, MSCo/miR-132-3p escaped the lysosomes via the H_II phase transition of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and decreased cellular reactive oxygen species (ROS) and apoptosis levels by regulating the RASA1/RAS/PI3K/AKT signaling pathway. In the transient middle cerebral artery occlusion (tMCAO) models, MSCo/miR-132-3p targeted impaired brain regions (approximately 9 times the accumulation of plain liposomes at 12 h), reduced cerebral vascular disruption, protected BBB integrity, and decreased infarct volume (from 44.95% to 6.99%).

OBJECTIVE: To develop and compare risk prediction models for in-hospital post-cardiac arrest brain injury (PCABI) in critically ill patients using nomograms and random forest algorithms, aiming to identify the optimal model for early identification of high-risk PCABI patients and providing evidence for precise treatment. METHODS: A retrospective cohort study was used to collect the first-time in-hospital cardiac arrest (IHCA) patients admitted to the intensive care unit (ICU) from 2008 to 2019 in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) as the study population, and the patients' age, gender, body mass, health insurance utilization, first vital signs and laboratory tests within 24 hours of ICU admission, mechanical ventilation, and critical care scores were extracted. Independent influencing factors of PCABI were identified through univariate and multivariate Logistic regression analyses. The included patients were randomly divided into a training cohort and an internal validation cohort in a 7:3 ratio, and the PCABI risk prediction model was constructed by the nomogram and random forest algorithm, respectively, and the model was evaluated by receiver operator characteristic curve (ROC curve), the calibration curve, and the decision curve analysis (DCA), and after the better model was selected, 179 patients admitted to Tianjin Medical University General Hospital as the external validation cohort for external evaluation were collected by using the same inclusion and exclusion criteria. RESULTS: A total of 1 419 patients with without traumatic brain injury who had their first-time IHCA were enrolled, including 995 in the training cohort (including 176 PCABI and 819 non-PCABI) and 424 in the internal validation cohort (including 74 PCABI and 350 non-PCABI). Univariate and multivariate analysis showed that age, potassium, urea nitrogen, sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation III (APACHE III), and mechanical ventilation were independent influences on the occurrence of PCABI in patients with IHCA (all P < 0.05). Combining the above variables, we constructed a nomogram model and a random forest model for comparison, and the results show that the nomogram model has better predictive efficacy than the random forest model [nomogram model: area under the ROC curve (AUC) of the training cohort = 0.776, with a 95% credible interval (95%CI) of 0.741-0.811; internal validation cohort AUC = 0.776, with a 95%CI of 0.718-0.833; random forest model: AUC = 0.720, with a 95%CI of 0.653-0.787], and they performed similarly in terms of calibration curves, but the nomogram performed better in terms of decision curve analysis (DCA); at the same time, the nomogram model was robust in terms of external validation cohort (external validation cohort AUC = 0.784, 95%CI was 0.692-0.876). CONCLUSIONS A nomogram risk prediction model for the occurrence of PCABI in critically ill patients was successfully constructed, which performs better than the random forest model, helps clinicians to identify the risk of PCABI in critically ill patients at an early stage and provides a theoretical basis for early intervention.
Humans ; Critical Illness ; Retrospective Studies ; Heart Arrest/complications* ; Nomograms ; Brain Injuries/etiology* ; Intensive Care Units ; Algorithms ; Male ; Female ; Middle Aged ; ROC Curve ; Risk Factors ; Risk Assessment ; Logistic Models ; Aged

Acupuncture treatment of chronic pain combined with depression (CPDC) is the result of a multi-target, multi-pathway approach. Acupuncture can treat CPDC by inhibiting the activation of glial cells, regulating the release of inflammatory mediators, regulating the expressions of neurotransmitters, changing the plasticity of neural synapses, regulating related epigenetic effects, regulating the microbiota-brain-gut axis, inhibiting nerve cell apoptosis, and antagonizing oxidative stress. The mechanism of its effect mainly involves anti-inflammatory related signaling pathways, regulation of neural synapse-related signaling pathways, and exerts its therapeutic effect through hippocampus, cerebral cortex, and amygdala.

Goiter is a kind of non-inflammatory and non-neoplastic hyperplasia and enlargement. Many studies have shown that substances such as thiocyanates and isothiocyanates can prevent the development of a variety of tumors. However, some studies have also found that such substances can lead to goiter. In this article, relevant information on common goitrogen in food are collected to explore their mechanism of action, laying a foundation for guiding residents to maintain a healthy and balanced diet.