ObjectiveBased on the theory of "spleen governing transportation and transformation"， this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice（AMR-AFI） in improving slow-transit constipation（STC）， as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis， thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group， model group， positive drug（mosapride） group（3 mg·kg^-1）， and low-， medium-， and high-dose groups of AMR-AFI（3.9， 7.8， 15.6 g·kg^-1）. Except for the control group， the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling， interventions were administered. All groups received continuous administration for 15 d， during which fecal samples， colon tissue， and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate， histological morphology of colonic tissue was observed via hematoxylin-eosin（HE） staining， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， and IL-2 in serum were detected using enzyme-linked immunosorbent assay（ELISA）. Furthermore， the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing， while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue， followed by gene ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses. Finally， Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group， the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased（P<0.01）， while serum levels of IL-6， TNF-α， and IL-2 were significantly elevated（P<0.01）. HE staining showed damage and shedding of colonic mucosal epithelial cells， along with a reduction in goblet cells in the model group. In comparison with the model group， all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6， TNF-α， and IL-2（P<0.01）. Among these， the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats（P<0.05， P<0.01）. Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group， as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis， such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice， increased species richness， downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella， and enriched beneficial and butyrate-producing bacteria， including Lachnospiraceae_NK4A136_group， Ruminococcaceae， and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast， pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota， arachidonic acid-mediated inflammatory metabolism， and aldosterone-regulated water-salt balance pathways.

ObjectiveBased on the theory of "spleen governing transportation and transformation"， this study investigates the efficacy of Atractylodis Macrocephalae Rhizoma processed with Aurantii Fructus Immaturus juice（AMR-AFI） in improving slow-transit constipation（STC）， as well as the synergistic regulatory mechanism involving the microbiota-metabolism axis， thereby elucidating the scientific basis of its processing theory. MethodsAnimals were randomly divided into the control group， model group， positive drug（mosapride） group（3 mg·kg^-1）， and low-， medium-， and high-dose groups of AMR-AFI（3.9， 7.8， 15.6 g·kg^-1）. Except for the control group， the remaining five groups were induced with STC using loperamide hydrochloride. Following modeling， interventions were administered. All groups received continuous administration for 15 d， during which fecal samples， colon tissue， and serum were collected. Constipation improvement was assessed by measuring fecal moisture content and small intestinal propulsion rate， histological morphology of colonic tissue was observed via hematoxylin-eosin（HE） staining， and the levels of interleukin（IL）-6， tumor necrosis factor（TNF）-α， and IL-2 in serum were detected using enzyme-linked immunosorbent assay（ELISA）. Furthermore， the microbial community structure in mouse feces was analyzed by 16S rRNA sequencing， while transcriptomic sequencing was employed to screen differentially expressed genes in colonic tissue， followed by gene ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses. Finally， Spearman correlation analysis was conducted to explore the association between differential microbiota and differential genes. ResultsCompared with the control group， the intestinal propulsion rate and fecal moisture content in the model group were significantly decreased（P<0.01）， while serum levels of IL-6， TNF-α， and IL-2 were significantly elevated（P<0.01）. HE staining showed damage and shedding of colonic mucosal epithelial cells， along with a reduction in goblet cells in the model group. In comparison with the model group， all treatment groups improved the pathological state of the colonic mucosa to varying degrees and reduced serum levels of IL-6， TNF-α， and IL-2（P<0.01）. Among these， the high-dose group of AMR-AFI significantly increased the intestinal propulsion rate and fecal moisture content of rats（P<0.05， P<0.01）. Further transcriptomic analysis revealed that a total of 104 differentially expressed genes were identified from comparisons between the model group and the control group， as well as between the model group and the high-dose group of AMR-AFI. These genes were mainly enriched in pathways closely related to STC pathogenesis， such as arachidonic acid metabolism and aldosterone-regulated sodium reabsorption. 16S rRNA sequencing results indicated that AMR-AFI reversed the structural imbalance of the gut microbiota in model mice， increased species richness， downregulated the relative abundance of pro-inflammatory bacteria such as Parasutterella， and enriched beneficial and butyrate-producing bacteria， including Lachnospiraceae_NK4A136_group， Ruminococcaceae， and Lachnospiraceae. Spearman correlation analysis further showed that the beneficial bacteria enriched in the AMR-AFI group were negatively correlated with genes involved in the arachidonic acid metabolic pathway and positively correlated with genes in the aldosterone-regulated sodium reabsorption pathway. In contrast， pro-inflammatory bacteria in the model group exhibited the opposite correlation trends. ConclusionAMR-AFI can effectively exert synergistic therapeutic effects on STC by regulating intestinal microbiota， arachidonic acid-mediated inflammatory metabolism， and aldosterone-regulated water-salt balance pathways.

ObjectiveTo investigate the effects of forkhead box protein O4 （FOXO4） expression on gastric precancerous lesions （GPL）， and to clarify its mechanism in mediating the therapeutic effect of Celastrus orbiculatus extract （COE） on GPL by regulating aerobic glycolysis. MethodsReferring to the previously established combined modeling protocol in our research group， a rat model of gastric precancerous lesions （GPL） was constructed through the following procedures： rats were given free access to 170 μg/mL N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） solution for ad libitum drinking， fed with a diet supplemented with 0.03% ranitidine hydrochloride， and treated with a cycling regimen of “2-day feeding followed by 1-day fasting”. Specifically， on the afternoon of each fasting day， the rats received intragastric administration of 2% sodium salicylate at a dose of 10 mL/kg body weight. FOXO4-silenced and overexpression model rats were constructed by tail vein injection of plasmids. The rats were randomly divided into control， model， COE， overexpression negative control （OE-NC）， FOXO4 overexpression （OE-FOXO4）， OE-FOXO4+COE， silencing negative control （shNC）， FOXO4 silencing （shFOXO4） and shFOXO4+COE groups. Gastric mucosal histopathological changes were observed in each group. Lactic acid content in gastric mucosal tissues was detected by colorimetry. The expression levels of FOXO4， HK2， PKM2， LDHA and GLUT1 were evaluated by immunohistochemistry （IHC）， and their mRNA levels were determined by RT-PCR.Results Compared with the control group， the COE， OE-FOXO4 and OE-FOXO4+COE groups exhibited significantly improved gastric mucosal lesions， reduced lactic acid levels， weakened expression of aerobic glycolysis-related proteins （PKM2， HK2， LDHA， GLUT1）， and enhanced FOXO4 expression. The OE-FOXO4+COE group showed the lowest lactic acid level and more pronounced changes in related protein expression compared with the COE and OE-FOXO4 groups. In contrast， the shFOXO4 and shFOXO4+COE groups displayed increased lactic acid levels， enhanced expression of aerobic glycolysis-related proteins， and reduced FOXO4 expression compared with the model group.ConclusionFOXO4 expression is involved in the inhibitory effect of COE on GPL， possibly by regulating the aerobic glycolysis process.

BACKGROUND: Mild cognitive impairment (MCI) is common in atrial fibrillation (AF) patients and may develop earlier in those with multiple cardiovascular comorbidities, potentially impairing self-management and treatment adherence. This study aimed to characterize the prevalence and profile of MCI in AF patients, examine its associations with cardiovascular comorbidities, and assess how these comorbidities influence specific cognitive domains. METHODS: This cross-sectional study analyzed data from AF patients who underwent cognitive assessment between 2017 and 2021. Cognitive status was categorized as MCI or non-MCI based on the Montreal Cognitive Assessment. Associations between comorbidities and MCI were assessed by logistic regression, and cognitive domains were compared using the Mann-Whitney U test. RESULTS: Of 4136 AF patients (mean age: 64.7 ± 9.4 years, 64.7% male), 33.5% of patients had MCI. Among the AF patients, 31.2% of patients had coronary artery disease, 20.1% of patients had heart failure, and 18.1% of patients had hypertension. 88.7% of patients had left atrial enlargement, and 11.0% of patients had reduced left ventricular ejection fraction. Independent factors associated with higher MCI prevalence included older age (OR = 1.04, 95% CI: 1.03-1.05, P < 0.001), lower education level (OR = 1.51, 95% CI: 1.31-1.73, P < 0.001), hypertension (OR = 1.28, 95% CI: 1.07-1.52, P = 0.001), heart failure (OR = 1.24, 95% CI: 1.04-1.48, P = 0.020), and lower left ventricular ejection fraction (OR = 1.43, 95% CI: 1.04-1.98, P = 0.028). A higher CHA₂DS₂-VASc score (OR = 1.27, 95% CI: 1.22-1.33, P < 0.001; ≥ 2 points vs. < 2 points), and greater atherosclerotic cardiovascular disease burden (OR = 1.45, 95% CI: 1.02-2.08, P = 0.040; 2 types vs. 0 type) were linked to increased MCI risk. These above factors influenced various cognitive domains. CONCLUSIONS MCI is common in AF and closely associated with cardiovascular multimorbidity. Patients with multiple comorbidities are at higher risk, highlighting the importance of routine cognitive assessment to support self-management and integrated care.

Cardiac arrest (CA) is a critical condition in the field of cardiovascular medicine. Despite successful resuscitation, patients continue to have a high mortality rate, largely due to post CA syndrome (PCAS). However, the injury and pathophysiological mechanisms underlying PCAS remain unclear. Experimental animal models are valuable tools for exploring the etiology, pathogenesis, and potential interventions for CA and PCAS. Current CA animal models include electrical induction of ventricular fibrillation (VF), myocardial infarction, high potassium, asphyxia, and hemorrhagic shock. Although these models do not fully replicate the complexity of clinical CA, the mechanistic insights they provide remain highly relevant, including post-CA brain injury (PCABI), post-CA myocardial dysfunction (PAMD), systemic ischaemia/reperfusion injury (IRI), and the persistent precipitating pathology. Summarizing the methods of establishing CA models, the challenges encountered in the modeling process, and the mechanisms of PCAS can provide a foundation for developing standardized CA modeling protocols.
Animals ; Disease Models, Animal ; Post-Cardiac Arrest Syndrome/physiopathology* ; Heart Arrest/physiopathology* ; Humans ; Ventricular Fibrillation/complications*

OBJECTIVES: To investigate the therapeutic mechanism of 2,6-dimethoxy-1,4-benzoquinone (DMQ) for alleviating dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. METHODS: Eighteen male C57BL/6J mice were equally randomized into control group, DSS group and DMQ treatment group. In DSS and DMQ groups, the mice were treated with DSS in drinking water to induce UC, and received intraperitoneal injections of sterile PBS or DMQ (20 mg/kg) during modeling. The changes in body weight, disease activity index (DAI), colon length, spleen weight, and colon histological scores of the mice were examined, and the percentages of Th17 and IFN-γ⁺ CD8⁺ T cells in the mesenteric lymph nodes and spleen were analyzed using flow cytometry. The expressions of tight junction proteins (Occludin and ZO-1), proteins associated with inflammasome activation (caspase-1 and p20), IL-1β and TNF-α in the colon tissues were detected using Western blotting or ELISA. In the cell experiment, mouse bone marrow-derived macrophages (BMDMs) primed with lipopolysaccharide (LPS) were treated with DMQ, followed by stmulation with nigericin to activate the classical NLRP3 inflammasome pathway. In cultured human peripheral blood mononuclear cells (PBMCs) treated with either LPS alone or LPS plus nigericin, the effects of DMQ on inflammasome activation, pyroptosis, and cytokine release were evaluated via Western blotting, ELISA, and flow cytometry. RESULTS: In DSS-treated mice, DMQ treatment significantly alleviated DSS-induced body weight loss, colon shortening, spleen enlargement, and colon inflammation. The DMQ-treated mice showed significantly reduced percentages of Th17 cells and IFN-γ⁺ CD8⁺ T cells in the mesenteric lymph nodes and spleen, with increased occludin and ZO-1 expressions and decreased caspase-1 expression in the colon tissue. DMQ obviously inhibited classical NLRP3 inflammasome activation in mouse BMDMs and both the classical and alternative pathways of NLRP3 activation in human PBMCs, causing also suppression of caspase-1-dependent pyroptosis. CONCLUSIONS DMQ ameliorates DSS-induced UC in mice by inhibiting NLRP3 inflammasome activation.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice, Inbred C57BL ; Colitis, Ulcerative/metabolism* ; Dextran Sulfate/adverse effects* ; Male ; Inflammasomes/metabolism* ; Mice ; Benzoquinones/therapeutic use* ; Th17 Cells ; Caspase 1/metabolism*

OBJECTIVE: To explore the clinical features of the sepsis in immunocompromised hosts and establish an early warning equation. METHODS: A retrospective study was conducted on sepsis patients admitted to the intensive care unit (ICU) of Binzhou Medical University Hospital from October 2011 to October 2022. General information, infection site, etiology results and drug susceptibility, clinical symptoms, inflammatory indicators, acute physiology and chronic health status evaluation II (APACHE II), sequential organ failure assessment (SOFA), incidence of immune paralysis, and outcome during hospitalization were collected. Based on whether they met the diagnostic criteria for immunocompromised hosts, patients were divided into immunocompromised group and immune normal group. The clinical information of the two groups were compared. Multivariate Logistic regression was used to analyze the risk factors of patients with immunocompromised sepsis and the regression equation model was initially established. Omnibus test and Hosmer-Lemeshow test were used to evaluate the model. RESULTS: A total of 169 patients with sepsis were included, including 61 in the immunocompromised group and 108 in the normal immune group. The top 3 infection sites in the immunocompromised group were bloodstream infection, pulmonary infection and abdominal infection. The top 3 infection sites in the normal immune group were pulmonary infection, bloodstream infection and abdominal infection. The infection rate of Gram-negative bacteria in the immunocompromised group was significantly lower than that in the normal group [49.2% (30/61) vs. 64.8% (70/108), P < 0.05]. The infection rate of Gram-positive bacteria [27.9% (17/61) vs. 13.9% (15/108)] and multidrug-resistant bacteria [54.1% (33/61) vs. 29.6% (32/108)] were significantly higher than those in normal immune group (both P < 0.05). In terms of clinical symptoms, the proportion of fever in the immunocompromised group was significantly lower than that in the immune normal group [49.2% (30/61) vs. 66.7% (72/108), P < 0.05]. Neutrophil count (NEU) and neutrophil percentage (NEU%) in the immunocompromised group were significantly lower than those in the normal immune group. Lymphocyte percentage (LYM%), neutrophil/lymphocyte ratio (NLR), C-reactive protein (CRP), procalcitonin (PCT), APACHE II score, combined shock rate, incidence of immune paralysis, and mortality during hospitalization in the immunocompromised group were significantly higher than those in the normal immune group. Logistic regression analysis showed that NLR, CRP and PCT were risk factors for patients with immunocompromised sepsis (all P < 0.05). The above indicators were used as covariables to construct a Logistic regression equation, that was, Logit (P) = 0.025X₁+0.010X₂+0.013X₃-2.945, where X₁, X₂ and X₃ represent NLR, CRP and PCT respectively. Omnibus test and Hosmer-Lemeshow test show that the model fits well and has certain early warning value. CONCLUSIONS Patients with immunocompromised sepsis have more intense inflammatory response, with Gram-negative bacteria being the predominant pathogen, and a higher incidence of Gram-positive bacterial infections and multi-drug resistant infections. The severity of the disease, in-hospital mortality, the incidence of shock and the incidence of immune paralysis after sepsis were significantly higher. NLR, CRP and PCT were independent risk factors for sepsis in immunocompromised hosts. The regression equation constructed based on this may have early warning significance for patients with immunocompromised sepsis.
Humans ; Sepsis/immunology* ; Immunocompromised Host ; Retrospective Studies ; Risk Factors ; Intensive Care Units ; Logistic Models ; Male ; APACHE ; Female ; Middle Aged ; Aged

Extracorporeal membrane oxygenation (ECMO) is primarily used in clinical practice to provide continuous extracorporeal respiratory and circulatory support for patients with severe heart and lung failure, thereby sustaining life. It is a key technology for managing severe heart failure and respiratory failure that are difficult to control. With the accumulation of clinical experience in ECMO for circulatory and/or respiratory support, as well as advancements in biomedical engineering technology, more portable and stable ECMO devices have been introduced into clinical use, benefiting an increasing number of critically ill patients. Although ECMO technology has become relatively mature, the timing of ECMO initiation, management of sudden complications, and monitoring and early warning of physiological indicators are critical factors that greatly affect the therapeutic outcomes of ECMO. This article reviews traditional methods and artificial intelligence techniques used in risk assessment related to ECMO, including the latest achievements and research hotspots. Additionally, it discusses future trends in ECMO risk management, focusing on six key areas: multi-center and prospective studies, external validation and standardization of model performance, long-term prognosis considerations, integration of innovative technologies, enhancing model interpretability, and economic cost-effectiveness analysis. This provides a reference for future researchers to build models and explore new research directions.
Extracorporeal Membrane Oxygenation ; Humans ; Artificial Intelligence ; Risk Assessment ; Respiratory Insufficiency/therapy* ; Heart Failure/therapy*

Objective:To investigate the effect of aortic root repair and replacement on the surgical effect and postoperative complications of Stanford type A aortic dissection.Methods:By retrospective case-control study, 190 patients with Stanford type A aortic dissection admitted to the Affiliated Hospital of Jining Medical College from August 2020 to December 2023.According to the different surgical treatment methods, they were divided into repair group ( n=65) and replacement group ( n=125). Patients in the repair group received aortic root repair, while patients in the replacement group received aortic root replacement, that was, Bentall operation. The surgical related indexes, surgical effect, postoperative outcome and mid-term survival rate of the two groups were compared. The measurement data conforming to the normal distribution were expressed by the mean standard deviation ( ± s), and the comparison between groups adopted t-test; The measurement data of skewed distribution were expressed by M( Q1, Q3), and the comparison between groups was conducted using the rank sum test. Counting data were expressed by the number of cases and percentage (%), and the comparison between groups was conducted by chi-square test or Fisher exact probability method. Results:There was no significant difference in distal aortic operation, cardiopulmonary bypass time, hypothermic circulatory arrest time and occlusion time between repair group and replacement group ( P>0.05).There was no significant difference in ventilator-assisted time, intensive care unit stay time, visual analogue score(VAS) after waking up and hospitalization time between repair group and replacement group ( P>0.05).There was no significant difference between the two groups in 30-days mortality rate after discharge (9.2% vs 11.2%) and postoperative complications (18.5% vs 22.4%) ( P>0.05). Kaplan-Meier survival curve analysis showed that there was no significant relationship between the medium-term survival rate of patients in repair group and replacement group ( χ2=0.46, P=0.500). During the follow-up period, one patient in the replacement group underwent reoperation, including Bentall operation, with an interval of 14 months. Conclusions:the choice of aortic root repair or replacement has no effect on the surgical effect and postoperative complications of Stanford A aortic dissection patients. The short-term and medium-term survival rate of aortic root repair is similar to that of replacement, and no patient received proximal surgery again during the follow-up period, which is feasible and safe.

Objective: To understand the current status of tuberculosis prevention and control knowledge and perceived stress among college and middle school students with pulmonary tuberculosis (PTB) in Yantai City, and to analyze the related factors, so as to provide a basis for the school to carry out health education and psychological counseling. Methods: A matched case control study was conducted, with 100 PTB student patients in junior high school and above who were diagnosed at designated medical institutions from October 2020 to October 2024. Four healthy control students of the same gender, same dormitory, or same class were selected for each case. Therefore, 100 cases and 400 controls were investigated by questionnaire. The following information was collected: personal basic information; tuberculosis prevention and control awareness; and scores of the Chinese Perceived Stress Scale (CPSS). Conditional Logistic regression model and mixed linear models were used to compare the PTB prevention and control awareness rate, as well as the perceived stress between the case and control groups. Multiple linear regression analysis was used to analyze the factors that may affect the perceived stress of students with PTB. Results: The awareness rates of four tuberculosis knowledge items (symptoms of PTB, main causes of onset after infection, consequences of PTB patients not receiving standardized and complete treatment, the most important method to prevent PTB) were higher in the case group (40.00%, 72.00% , 38.00%, 49.00%) than the control group (21.50%, 57.50%, 22.25%, 31.25%) and the differences were statistically significant ( Wald χ 2=18.44, 8.78, 13.20, 16.89, all P <0.01). The tension score (10.49±4.20), loss of control score ( 11.21± 4.58), and total score (21.70±6.88) in the case group were higher than the control group (9.35±4.73, 9.75±5.60, 19.09±8.36) and the differences were statistically significant ( t =2.21, 2.42, 2.88, all P <0.05). The results of multiple linear regression analysis showed that age ≥ 18 years and family history of tuberculosis were the related factors affecting the overall perceived stress and tension of college and middle school students with PTB ( B total scores =4.50, 5.91; B tension score =2.39, 3.23, all P <0.05). Conclusions The tuberculosis prevention and control awareness rate, and the perceived stress of college and middle school students with PTB in Yantai are both higher than students without tuberculosis. Moreover, the perceived stress of students with PTB who are aged ≥18 years or have a family history of tuberculosis is even higher.