ObjectiveThis study aimed to investigate the action mechanism by which Banxia Xiexintang （BXT） inhibits epithelial-mesenchymal transition （EMT） in chronic atrophic gastritis （CAG） rats by regulating the interleukin-17（IL-17）/extracellular regulated protein kinases（ERK）/CCAAT enhancer binding protein β（C/EBPβ）signaling pathway， thereby providing new theoretical evidence for the treatment of CAG with classic traditional Chinese medicine formulas. MethodsA CAG rat model was established by using the combined factor method. After successful modeling， the rats were randomly divided into the model group， low-， medium-， and high-dose groups （0.549， 1.098， 2.196 g·kg^-1， respectively） of BXT， and the positive drug group （vitacoenzyme， 0.3 g·kg^-1）. A normal control group was also set up. After 8 weeks of intervention， the pathological changes of gastric tissue were evaluated. The enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of IL-17， tumor necrosis factor-α （TNF-α）， cyclooxygenase-2 （COX-2）， and C/EBPβ in serum， as well as the contents of EMT markers in gastric mucosal tissue including E-cadherin， N-cadherin， and vimentin. The immunohistochemistry method was employed to determine the localization and protein expression levels of IL-17， p-ERK， and C/EBPβ in gastric mucosal tissue. Western blot was used to detect the protein expressions of C/EBPβ， ERK， and its phosphorylated form （p）-ERK in gastric mucosa. Real-time polymerase chain reaction （Real-time PCR） was applied to measure the mRNA expression levels of ERK， COX-2， and C/EBPβ in gastric mucosa. ResultsCompared with those in the normal control group， the rats in the model group showed gastric mucosal glandular atrophy and inflammatory cell infiltration. The protein and their related mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly increased （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBPβ in serum were significantly increased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosal tissue were significantly increased， while the content of E-cadherin was significantly decreased （P<0.01）. Compared with the model group， after intervention with different doses of BXT， the pathological damage of the gastric mucosa was improved to varying degrees. The protein and mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly reduced （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBP β in serum were significantly decreased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosa tissue were decreased， while the content of E-cadherin was increased （P<0.05，P<0.01）. ConclusionBXT can effectively improve the pathological damage of gastric mucosal tissue in CAG rats. Its action mechanism may be related to reducing the levels of IL-17 and TNF-α in serum， regulating the IL-17/ERK/C/EBPβ signaling pathway and inhibiting the EMT process.

Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Background Per- and poly-fluoroalkyl substances (PFAS) can influence gestational diabetes mellitus (GDM); however, current studies on their association are limited and have yielded inconsistent findings. Objective To investigate the association between maternal exposure to PFAS, as measured by urinary concentrations in early pregnancy, and the risk of developing GDM. Methods Based on the Wuhu Birth Cohort in Anhui Province conducted between 2020 and 2023, this study included 1910 pregnant women. Urine samples were collected during the first trimester, and a 75 g oral glucose tolerance test (OGTT) was completed at 24–28 gestational weeks. The concentrations of six PFAS in urine were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Participants were categorized into low, medium, and high exposure groups according to tertiles of individual PFAS concentrations. Logistic regression analysis was employed to assess the potential impact of early-pregnancy PFAS exposure levels on the risk of GDM, with stratified analyses by maternal age and fetal sex. A generalized weighted quantile sum regression (gWQS) model was applied to evaluate the relative weight distribution of the six PFAS in their mixture effect. Results The logistic regression results revealed that both medium exposure to perfluorohexane sulfonate (PFHxS) (OR=1.475, 95%CI: 1.040, 2.093) and high exposure to perfluorononanoic acid (PFNA) (OR=1.430, 95%CI: 1.013, 2.018) were positively associated with diagnosed GDM. This association was more pronounced among women older than 28 years. Among pregnant women carrying male fetuses, high-level exposures to per fluorohexanoic acid (PFHxA) (OR=1.708, 95%CI: 1.006, 2.899) and PFHxS (OR=2.116, 95%CI: 1.247, 3.584) showed positive associations with diagnosed GDM. In contrast, among those carrying female fetuses, moderate perfluorooctanesulfonic acid (PFOS) exposure was associated with a lower risk of GDM (OR=0.542, 95%CI: 0.311, 0.946). The gWQS results demonstrated that PFOS (0.48) and perfluorobutane sulfonate (PFBS) (0.34) contributed the most to the mixture effect. Conclusion Early-pregnancy exposure to PFAS (particularly PFHxS and PFNA) may be an etiological factor for GDM, with maternal age and fetal sex potentially acting as effect modifiers in this association.

Objective To investigate the potential protective mechanism of tanshinone ⅡA against acetaminophen （APAP）-induced acute liver injury. Methods Thirty mice were randomly divided into the normal group, model group, low-dose tanshinone ⅡA group （5 mg/kg）, medium-dose tanshinone ⅡA group （10 mg/kg） and high-dose tanshinone ⅡA group （20 mg/kg）. All groups were intragastrically administered once daily for 7 consecutive days. On the 7th day, except for the normal group, mice in the remaining groups were intraperitoneally injected with 400 mg/kg APAP to establish the acute lung injury （ALI） model. The protective effect of tanshinone ⅡA was evaluated based on the liver weight ratio, the levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）, and HE staining. Targets of tanshinone ⅡA were predicted by the Traditional Chinese Medicine Systems Pharmacology （TCMSP）, and a shared target protein-protein interaction （PPI） network was constructed by Search Tool for the Retrieval of Interacting Genes/Proteins （STRING） 11.5 in combination with disease targets from GeneCards. The Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed by Database for Annotation, Visualization and Integrated Discovery （DAVID）, and the component-target-pathway network was constructed. The molecular docking between tanshinone ⅡA and the core targets was performed by AutoDock and visualised. Results Compared with the normal group, the liver weight ratio and serum aminotransferase level of mice with acute liver injury were significantly elevated （P<0.05）, and the pathological injury of liver tissue was obvious. After tanshinone ⅡA treatment, the above index were significantly reduced （P<0.05）, and the pathological injury was significantly improved. Further network pharmacological analysis was carried out and found that KEGG pathway enrichment analysis focused on IL-17 signaling pathway and tumor necrosis factor （TNF） signaling pathway, etc. In addition, the PPI core network showed that the key targets of tanshinone ⅡA to ameliorate acute liver injury mainly included TP53, AKT1, SRC, TNF and JUN. The molecular docking results showed that tanshinone ⅡA had high binding scores with the targets of MMP9, NFKB1, TNF, EP300 and SMAD3; and was able to bind to the targets of TP53, AKT1, SRC and JUN. Conclusion Tanshinone ⅡA may play a protective role against acute liver injury by regulating genes such as AKT1, JUN and TNF, and participating in signaling pathways such as TNF and IL-17.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

ObjectiveTo investigate the effect of Yiqi Yangyin Jiedu Huayu prescription on minimal hepatic encephalopathy in liver cirrhosis based on intestinal metabolomics. MethodsA total of 11 patients with liver cirrhosis who were hospitalized in Beijing Ditan Hospital， Capital Medical University， from March to May 2024， and were diagnosed with MHE based on psychometric hepatic encephalopathy score were enrolled as subjects， and 11 healthy family members of the patients were enrolled as control group. Fecal samples were collected for metabolomics analysis from the control group and the patients with MHE before and after treatment with Yiqi Yangyin Jiedu Huayu prescription， and a population cohort study was conducted to investigate the effect of Yiqi Yangyin Jiedu Huayu prescription on intestinal metabolism of patients with MHE. The Fisher’s exact test was used for categorical data between two groups； the independent samples t-test was used for comparison of normally distributed continuous data between two groups， the paired t-test was used for comparision before and after treatment within the same group， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. ResultsA total of 29 differentially expressed metabolites were detected between the MHE group and the control group， mainly amino acids， organic acids， organic amines， carbohydrates， fatty acids， and vitamins， and there were 12 upregulated metabolites and 17 downregulated metabolites in the MHE group， which were mainly enriched in the metabolic pathways of ornithine， branched-chain amino acid， and aromatic amino acid. After the treatment with Yiqi Yangyin Jiedu Huayu prescription， 80 differentially expressed metabolites were detected in the patients with MHE， mainly carbohydrates， organic acids， and amino acids， and there were 56 upregulated metabolites and 24 downregulated metabolites， which were mainly enriched in the metabolic pathways of ornithine， branched-chain amino acid， and aromatic amino acid. ConclusionYiqi Yangyin Jiedu Huayu prescription can exert a therapeutic effect on patients with MHE by regulating intestinal metabolism.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

[Objective] To investigate the seroprevalence characteristics of hepatitis E virus (HEV) among blood donors with hepatitis B virus (HBV) infection, so as to provide data support for the monitoring, prevention and treatment of HEV. [Methods] From January to December 2022, 219 samples positive for hepatitis B surface antigen (HBsAg), 142 occult hepatitis B virus infection (OBI) samples (HBV group) and 873 samples tested negative (control group) were collected. 361 samples were further tested with viral load assay and serological testing for five serological markers (HBsAg, HBsAb, HBeAg, HBeAb and HBcAb), and the DNA load was measured using real time fluorescence quantitative PCR. Commercially available enzyme-linked immunosorbent assays (ELISA) were used for the detection of anti-HEV IgG, anti-HEV IgM and HEV antigen (Ag). The Chi-square test or Fisher's exact test was used to assess the differences in the reactivity rates of anti-HEV IgG and anti-HEV IgM among different blood donor populations and different variables. Multivariable logistic regression was used to examine potential risk factors associated with anti-HEV IgG seroprevalence. [Results] In the HBV group, HBsAg positive donors exhibited low expression of antigen. The HBV DNA load of OBI infected donors ranged from 1 to 131.43 IU/mL (median 11.24 IU/mL). The prevalence of anti-HEV IgG and IgM antibody in the HBV group were 34.63% and 1.11%, respectively. Among them, the prevalence of anti-HEV IgG and anti-HEV IgM in the HBV group was 34.63% and 0, respectively (P<0.05), while in the OBI donors, they were 41.55% and 2.82%, respectively. In the normal donors, the reactivity rates for anti-HEV IgG and anti-HEV IgM were 18.67% and 1.49%, respectively. Statistical analysis showed that there was a difference in the reactivity rate of anti-HEV IgG between the HBV-infected donors and the normal donors (34.63% vs 18.67%, P<0.05), but no difference in the reactivity rate of anti-HEV IgM (1.11% vs 1.49%, P>0.05). No HEV Ag was detected in either group of blood donors. Multivariate logistic regression analysis indicated that age was an independent risk factor for anti-HEV IgG reactivity in both groups of blood donors. [Conclusion] The reactivity rate of anti-HEV IgG among HBV-infected blood donors was significantly higher than that in the normal donors in Wuhan, with age being an independent risk factor. Therefore, for HBV-infected donors, it is essential to strengthen and prioritize the prevention and treatment of HEV to reduce the spread of HEV.

By analyzing the current application of multi-modal data in the diagnosis of gastric "inflammation-cancer" transformation， this study explored the feasibility and strategies for constructing a disease-syndrome integrated diagnosis and treatment system. Based on traditional Chinese medicine （TCM） phenomics， we proposed utilizing multi-modal data from literature research， cross-sectional studies， and cohort follow-ups， combined with artificial intelligence technology， to establish a multi-dimensional diagnostic and treatment index system. This approach aims to uncover the complex pathogenesis and transformation patterns of gastric "inflammation-cancer" progression. Additionally， by dynamically collecting TCM four-diagnostic information and modern medical diagnostic information through a long-term follow-up system， we developed three major modules including information extraction， multi-modal phenotypic modeling， and information output， to make it enable real-world clinical data-driven long-term follow-up and treatment of chronic atrophic gastritis. This system can provide technical support for clinical diagnosis， treatment evaluation， and research， while also offering insights and methods for intelligent TCM diagnosis.