1.Mechanism of Xixintang in Protecting Blood-brain Barrier in Alzheimer's Disease Model Rats Based on AQP4 Polarization
Siyuan JIA ; Yongchang DIWU ; Yuan TIAN ; Jie GAO ; Meirong WU ; Dengkun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):1-10
ObjectiveThis paper aims to investigate the effects of Xixintang on aquaporin-4 (AQP4) polarity distribution, blood-brain barrier (BBB) function, and neuroinflammationin rats with Alzheimer's disease (AD), thereby revealing the potential mechanism through which this formula protects the BBB by regulating AQP4 polarization. The aim is to provide a scientific basis for clinical treatment. MethodsSixty Sprague-Dawley (SD) rats were randomly divided into a normal group, a model group, a probiotic group, a donepezil group, and an Xixintang group. The model was established by intraperitoneal injection of D-galactose (D-Gal) combined with bilateral intracerebroventricular injection of amyloid-β25-35 (Aβ25-35). The probiotic group (30.85 mg·kg-1), donepezil group (0.88 mg·kg-1), and Xixintang group (1.174 g·kg-1) received daily gavage administration, while the normal and model groups received intragastric administration with an equal volume of normal saline for one month. Cognitive ability was assessed by using the Morris water maze. BBB permeability was detected via Evans blue extravasation. The contents of interleukin-6 (IL-6), amyloid-β1-42 (Aβ1-42), and tumor necrosis factor-α (TNF-α) in the hippocampal tissues were measured by enzyme-linked immunosorbent assay (ELISA). The protein expressions of zonula occludens-1 (ZO-1), occludin, tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), and AQP4 in the hippocampal tissues were detected by western blot. The expression and co-localization levels of Aβ1-42, ionized calcium-binding adapter molecule 1 (IBA1), and AQP4/platelet endothelial cell adhesion molecule 31 (CD31) in the hippocampal region were examined by immunofluorescence. ResultsCompared with the normal group, the model group exhibited a significant decline in cognitive ability (P<0.01) and a marked increase in Evans blue extravasation in the brain (P<0.01). The expressions of ZO-1, occludin, and TIMP-1 were significantly decreased (P<0.01), while the expressions of AQP4 and MMP-9 were significantly increased (P<0.01). The co-localization level of AQP4/CD31 was significantly reduced (P<0.01), and the expressions of Aβ1-42, IL-6, TNF-α, and IBA1 were significantly elevated (P<0.01). Compared with the model group, the Xixintang group showed significant improvement in cognitive ability (P<0.01) and a significant reduction in Evans blue extravasation in the brain (P<0.01). The expressions of occludin, TIMP-1, and ZO-1 were significantly increased (P<0.05, P<0.01), while the expressions of AQP4 and MMP-9 were significantly decreased (P<0.05). The co-localization level of AQP4/CD31 was significantly enhanced (P<0.01), and the expressions of Aβ1-42, IL-6, TNF-α, and IBA1 were significantly reduced (P<0.05, P<0.01). ConclusionXixintang may improve cognitive function and alleviate AD pathology in AD model rats by regulating AQP4 polarity distribution, thereby breaking the vicious cycle of "Aβ deposition-neuroinflammation-BBB damage" and restoring the homeostasis of the microenvironment in the brain.
2.Effect of Xixintang on Colonic Mucosal Barrier and TLR4 /NF-κB p65 Signaling Pathway in AD Model Rats Induced by D-galactose Combined with Aβ25-35
Yuan TIAN ; Yongchang DIWU ; Siyuan JIA ; Jie GAO ; Meirong WU ; Dengkun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):1-11
ObjectiveThis study aims to investigate whether Xixintang could ameliorate cognitive dysfunction in an Alzheimer's disease (AD) rat model induced by D-galactose and β-amyloid (Aβ25-35), by means of repairing the colonic mucosal barrier, regulating the Toll-like receptor 4 (TLR4)/nuclear factor-κB p65 (NF-κB p65) signaling pathway, and intervening in the pathological process mediated by the gut-brain axis. MethodsSixty specific pathogen-free (SPF) male Sprague-Dawley (SD) rats were randomly divided to five groups (n=12): A control group, a model group, a donepezil group, an Xixintang group, and a probiotic group. Except for those in the control group, rats in all other groups received daily intraperitoneal injections of D-galactose for six consecutive weeks. Subsequently, aggregated Aβ25-35 was injected stereotactically into the bilateral ventricles to establish the AD model. During the intervention periods, the rats in all groups were administered their respective drugs and normal saline by gavage. The Morris water maze test was used to assess the capacity for spatial learning and memory. Hematoxylin-eosin (HE) staining was employed to observe the histopathological changes in the colon tissues. Immunofluorescence was used to detect Aβ1-41 deposition in the hippocampal region and Mucin 2 (MUC2) expression in the colonic mucosa. Western blot was performed to measure the protein expression levels of FFAR2,TLR4, NF-κB p65, occludin (OCLN), zonula occludens-1 (ZO-1), and MUC2 in the colonic tissues. Enzyme-linked immunosorbent assay (ELISA) was used to determine the contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), serum amyloid A (SAA), and Aβ1-42 in the hippocampal region from the colonic tissues. The lipopolysaccharide (LPS) concentrations in colon tissues of rats were measured by using a dynamic chromogenic limulus assay. ResultsCompared with those in the control group, the rats in the model group exhibited a significantly prolonged escape latency and a markedly shorter duration in the target quadrant (P<0.01). The integrity of the colonic mucosal structure was compromised, with disordered gland arrangement and a reduced number of goblet cells. The Aβ1-42 deposition in the hippocampal region was significantly increased (P<0.01). The protein expression levels of TLR4 and NF-κB p65 in colonic tissues were significantly upregulated (P<0.01), while those of occludin and ZO-1 were downregulated (P<0.01). The contents of inflammatory factors such as IL-6, TNF-α, and SAA were significantly elevated (P<0.01), and the LPS level in the serum was markedly increased (P<0.01). In comparison to those in the model group, the rats in the Xixintang group showed a significantly shortened escape latency and a prolonged duration in the target quadrant (P<0.01). The colonic mucosal structure was ameliorated, with neat gland arrangement and an increased number of goblet cells. The Aβ1-42 deposition in the hippocampal region was reduced (P<0.01). The protein expressions of TLR4 and NF-κB p65 in the colon tissues were decreased (P<0.05,P<0.01), while the protein levels of occludin and ZO-1 were increased (P<0.01). The contents of IL-6, TNF-α, and serum amyloid A (SAA) were decreased (P<0.01), and the LPS level was reduced (P<0.01). ConclusionXixintang can significantly ameliorate cognitive dysfunction of AD model rats, by means of restoring the colonic mucosal barrier structure, reducing cerebral Aβ deposition, and suppressing peripheral and central inflammatory response. Its mechanism of action may be closely associated with the suppression of the TLR4/NF-κB signaling pathway activation, reduction of endotoxin levels, and regulation of the gut-brain axis.
3.Effect of Xixintang on Colonic Mucosal Barrier and TLR4 /NF-κB p65 Signaling Pathway in AD Model Rats Induced by D-galactose Combined with Aβ25-35
Yuan TIAN ; Yongchang DIWU ; Siyuan JIA ; Jie GAO ; Meirong WU ; Dengkun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):1-11
ObjectiveThis study aims to investigate whether Xixintang could ameliorate cognitive dysfunction in an Alzheimer's disease (AD) rat model induced by D-galactose and β-amyloid (Aβ25-35), by means of repairing the colonic mucosal barrier, regulating the Toll-like receptor 4 (TLR4)/nuclear factor-κB p65 (NF-κB p65) signaling pathway, and intervening in the pathological process mediated by the gut-brain axis. MethodsSixty specific pathogen-free (SPF) male Sprague-Dawley (SD) rats were randomly divided to five groups (n=12): A control group, a model group, a donepezil group, an Xixintang group, and a probiotic group. Except for those in the control group, rats in all other groups received daily intraperitoneal injections of D-galactose for six consecutive weeks. Subsequently, aggregated Aβ25-35 was injected stereotactically into the bilateral ventricles to establish the AD model. During the intervention periods, the rats in all groups were administered their respective drugs and normal saline by gavage. The Morris water maze test was used to assess the capacity for spatial learning and memory. Hematoxylin-eosin (HE) staining was employed to observe the histopathological changes in the colon tissues. Immunofluorescence was used to detect Aβ1-41 deposition in the hippocampal region and Mucin 2 (MUC2) expression in the colonic mucosa. Western blot was performed to measure the protein expression levels of FFAR2,TLR4, NF-κB p65, occludin (OCLN), zonula occludens-1 (ZO-1), and MUC2 in the colonic tissues. Enzyme-linked immunosorbent assay (ELISA) was used to determine the contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), serum amyloid A (SAA), and Aβ1-42 in the hippocampal region from the colonic tissues. The lipopolysaccharide (LPS) concentrations in colon tissues of rats were measured by using a dynamic chromogenic limulus assay. ResultsCompared with those in the control group, the rats in the model group exhibited a significantly prolonged escape latency and a markedly shorter duration in the target quadrant (P<0.01). The integrity of the colonic mucosal structure was compromised, with disordered gland arrangement and a reduced number of goblet cells. The Aβ1-42 deposition in the hippocampal region was significantly increased (P<0.01). The protein expression levels of TLR4 and NF-κB p65 in colonic tissues were significantly upregulated (P<0.01), while those of occludin and ZO-1 were downregulated (P<0.01). The contents of inflammatory factors such as IL-6, TNF-α, and SAA were significantly elevated (P<0.01), and the LPS level in the serum was markedly increased (P<0.01). In comparison to those in the model group, the rats in the Xixintang group showed a significantly shortened escape latency and a prolonged duration in the target quadrant (P<0.01). The colonic mucosal structure was ameliorated, with neat gland arrangement and an increased number of goblet cells. The Aβ1-42 deposition in the hippocampal region was reduced (P<0.01). The protein expressions of TLR4 and NF-κB p65 in the colon tissues were decreased (P<0.05,P<0.01), while the protein levels of occludin and ZO-1 were increased (P<0.01). The contents of IL-6, TNF-α, and serum amyloid A (SAA) were decreased (P<0.01), and the LPS level was reduced (P<0.01). ConclusionXixintang can significantly ameliorate cognitive dysfunction of AD model rats, by means of restoring the colonic mucosal barrier structure, reducing cerebral Aβ deposition, and suppressing peripheral and central inflammatory response. Its mechanism of action may be closely associated with the suppression of the TLR4/NF-κB signaling pathway activation, reduction of endotoxin levels, and regulation of the gut-brain axis.
4.Propensity score matching in observational studies:methods and applications
Ye WU ; Jie TIAN ; Wei-bing WANG
Fudan University Journal of Medical Sciences 2025;52(6):917-922
Observational studies are important approaches for obtaining real-world evidence.However,due to the lack of randomized allocation,differences in baseline characteristics between groups often introduce confounding bias,which may distort the results.Traditional stratified analyses and multivariable regression models have limited ability to control confounding when multiple covariates are involved.Propensity score matching estimates the probability of receiving an intervention based on observed covariates,then matches individuals with similar propensity scores between treatment and control groups,thereby balancing covariate distributions and reducing confounding.In recent years,propensity score matching has been widely applied in various fields,including chronic disease management and drug effectiveness evaluation,public health policy and health service assessment,vaccine effectiveness studies focusing on population disparities,and evaluations of telemedicine interventions.This review summarizes common matching methods and application scenarios of propensity score matching in observational studies.
5.Recent advances on the role of ferroptosis in diabetic retinopathy
Xiaoyu HOU ; Ziqiang LIU ; Xuqi BI ; Yinde TIAN ; Jingying WANG ; Chuanhong JIE
Recent Advances in Ophthalmology 2025;45(12):991-996
Iron,a vital trace element and redox-active metal in the human body,is pivotal in cellular processes and en-gages in a multitude of biological reactions.Ferroptosis,an emerging form of regulated cell death,is predominantly instiga-ted by the excessive free iron that catalyzes reactive oxygen species(ROS)production via the Fenton reaction.This process results in the peroxidation of polyunsaturated fatty acids within the cellular lipid membrane,compromising the membrane's integrity and thereby inducing ferroptosis.In the context of diabetic retinopathy(DR),ferroptosis plays a sig-nificant role.The disruption of iron metabolism,the excessive accumulation of ROS,and the imbalance of the antioxidant system are key mechanisms contributing to ferroptosis in retinal tissues and the exacerbation of DR's pathological progres-sion.This review provides a systematic summary and in-depth discussion of the advancements in understanding the role of ferroptosis in DR pathogenesis,intending to offer valuable insights for future research endeavors in this field.
6.Correlation between triglyceride glucose index and prognosis in elderly patients with unstable angina
Xiang ZHOU ; Ruihan LIU ; Yutong LIU ; Fan TIAN ; Jie ZHANG ; Xiaomao WANG ; Jian CAO
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(2):136-139
Objective To explore the correlation between triglyceride glucose(TyG)index and per-cutaneous coronary intervention(PCI)following drug treatment in elderly patients with unstable angina pectoris(UAP).Methods A total of 221 elderly UAP patients admitted to the Hyperbaric Oxygen Department of the First Medical Center of Chinese PLA General Hospital from March 2016 to March 2024 were enrolled,and based on the tertiles of the TyG index,they were divided into low,medium and high TyG index groups(the index:≤8.48,8.49-8.92,>8.92;with 74,74 and 73 cases,respectively).Clinical data of all patients were collected,and whether undergoing PCI after discharge was defined as the endpoint event.The follow-up ended on May 10,2024.The clini-cal data were compared in the three groups.Kaplan-Meier survival curves were plotted to compare the survival rates among the groups,and Cox proportional hazards regression model was em-ployed to analyze the influencing factors for occurrence of endpoint event.Results There were significant differences in the three groups in terms of TyG index,BMI,diabetes,FPG,TC,TG,LDL-C,HDL-C,HbA1c,NT-proBNP,and incidence of endpoint event(P<0.05,P<0.01).Univa-riate Cox proportional hazards regression analysis showed that the TyG index,diabetes,and HbA1c were risk factors for endpoint events in elderly patients with UAP(HR=2.523,95%CI:1.593-3.996;HR=2.543,95%CI:1.263-5.118;HR=1.434,95%CI:1.159-1.774).Further multivariate Cox proportional hazards regression analysis showed that,after adjusting for diabetes and HbA1c,the TyG index was an independent risk factor for PCI after discharge in UAP patients(HR=2.023,95%CI:1.209-3.384).Conclusion In elderly UAP patients receiving drug treat-ment,a high TyG index is positively correlated with undergoing PCI after discharge,and the index is an independent risk factor for PCI in them.
7.Correlation between intrinsic capacity and triglyceride-glucose index in older adults from a Chinese community
Ruihan LIU ; Yutong LIU ; Xiang ZHOU ; Xiaomao WANG ; Jie ZHANG ; Fan TIAN ; Jian CAO
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(4):445-449
Objective To investigate the relationship of TyG index and IC.Methods A cross-sectional study was conducted with 1000 older adults living in Wanshou Road Community from May to December 2023.Finally 820 participants were enrolled,and based on the TyG index,they were divided into lower TyG index group(≤7.349,404 cases)and higher TyG index group(>7.349,416 cases).After PSM,there were only 522 participants subjected,including 261 individuals in the lower TyG index group 1 (≤7.349)and 416 ones in the higher TyG index group 2(>7.349).Univariate and multivariate logistic regression analyses were used to assess the correlation between IC and the TyG index as both continuous and categorical variables.PSM was employed to eliminate the confounding effects of covariates to identify the relationship between TyG index and IC in different categories.Results Before PSM,the neutrophil count,WBC count,and Hcy,FPG,TC,TG and HbA1c levels were significantly lower,and lymphocyte count,monocyte count,and AST level were obviously higher in the low TyG index group than the high TyG index group(P<0.05,P<0.01).After PSM,the low TyG index group still had notably lower FPG,TG and HbA1c than the high TyG index group(P<0.05,P<0.01).ROC curve analysis revealed that the cutoff value of TyG index was 7.349.Taking 7.349 as the cutoff value and TyG index as the cate-gorical variable,multivariate logistic regression analysis displayed that TyG index was correlated with IC[OR=3.921,95%CI:2.800-5.491,P=0.001(Model 1);OR=2.744,95%CI:1.739-4.329,P=0.001(Model 2);OR=2.744,95%CI:1.805-4.171,P=0.001(Model 3);OR=2.722,95%CI:1.530-4.843,P=0.001(after PSM)],indicating that TyG index remains an independent risk factor for IC.Conclusion IC is still correlated with TyG index in community-dwelling elderly individuals under different baseline conditions after adjusting for relevant laboratory indicators.As an indicator generated from routine blood test,TyG index has advantages in terms of cost and time.With further validation,TyG may provide a direction for studying IC prediction.
8.Analysis of the Path to Improve the Efficiency of Medical Resource Allocation in Chinese Medicine Hospitals under the Perspective of fsQCA Configuration
Xueyun TIAN ; Zhixin WANG ; Yiru ZHOU ; Yan JIANG ; Liying ZHAO ; Jie ZHOU ; Zi YANG ; Xiaowei MAN
Chinese Hospital Management 2025;45(1):41-45
Objective To explore the optimisation path of medical resource allocation efficiency improvement in Traditional Chinese Medicine (TCM) hospitals under the synergistic effect of multiple factors,so as to provide powerful support for the balanced development of medical resources in TCM hospitals.Methods The comprehensive efficiency of resource allocation in TCM hospitals in 31 provinces (cities and districts) of China obtained by Data Envelopment Analysis was taken as the outcome variable,and with the help of Fuzzy-set Qualitative Comparative Analysis,it examined the configurations of efficient medical resource allocation,considering the following conditional variables:per capital Regional GDP,the proportion of fiscal allocation revenue to total income,the ratio of TCM practicing (assistant) physicians to all practicing (assistant) physicians,the average length of hospital stay for discharged patients,the number of total diagnosis and treatments per thousand population,and the number of hospital beds per thousand population.Results By analyzing the conditional patterns of efficient allocation of medical resources in TCM hospitals,three equivalent driving paths can be summarized,which are comprehensive service capacity,TCM advantage and hospitalization driving paths.Conclusion The overall level of medical resource allocation efficiency of TCM hospitals in China needs to be improved.In the future,efforts should be made to improve the comprehensive service capacity and operational efficiency of hospitals,give full play to the advantages of TCM,build a high-quality TCM talent team,reasonably shorten the average hospital stay,and improve the utilization efficiency of hospital beds.
9.Innovative clinical trial designs for vaccine development
Dan-ni ZHAO ; Zhuo-ying HUANG ; Jie TIAN ; Tao ZHANG ; Wei-bing WANG
Fudan University Journal of Medical Sciences 2025;52(2):311-316
During sudden outbreaks of major infectious diseases,traditional vaccine clinical trials often fail to deliver timely and meaningful outcomes.To address this,innovative trial designs are essential to accelerate or restructure the traditional three-phase clinical trial process while maintaining adherence to scientific principles of drug candidate safety and efficacy.This paper presents various innovative vaccine clinical trial designs and concepts,along with critical considerations for their application,to serve as a methodological reference for related research.Adaptive designs provide flexibility by dynamically adjusting trial parameters—such as dose selection,population stratification,and sample size reestimation—based on interim analysis results.Bayesian designs incorporate historical data and prior information,reducing sample size requirements.Master protocol designs enable the evaluation of multiple treatments or target populations within a unified framework,significantly improving efficiency.Additionally,real-world data(RWD),including electronic health records vaccination records and insurance claims,supports the creation of virtual control groups,addressing ethical concerns while enhancing trial feasibility.A hybrid design combining randomized controlled trials(RCTs)with RWD is also proposed to leverage the strengths of both methodologies.These innovative designs optimize the research process,accelerating vaccine development and regulatory approval.By integrating these approaches,robust evidence-based insights can be generated,advancing precision medicine goals and strengthening public health responses to emerging infectious diseases.
10.Dynamic electrical impedance tomography imaging algorithm based on complementary information fusion network
Xin-yi WANG ; Tao ZHANG ; Xiang TIAN ; Ning YANG ; Jun-jie DU ; Xue-chao LIU ; Feng FU ; Xue-tao SHI ; Can-hua XU
Chinese Medical Equipment Journal 2025;46(6):1-6
Objective To propose a dynamic electrical impedance tomography imaging algorithm based on complementary information fusion network(CIFN)to enhance image quality of dynamic electrical impedance imaging.Methods There were three modules for initialization,multi-frame complementary information extraction and information fusion involved in the CIFN.Firstly,multi-frame dynamic conductivity distribution images were obtained by the initialization module;secondly,spatial complementary information was extracted from the images by using the multi-frame complementary information extraction module;finally,the fusion of lesion target distribution information and target re-reconstruction were realized by the information fusion module to aquire high-quality EIT images.With a 16-electrode multilayer cranial simulation model,the CIFN-based imaging method was compared with Tikhonov regularization algorithm,spectral constraint algorithm and U-Net algorithm in terms of imaging results of types of lesions to verify its performance.Results Compared with the Tikhonov regularization algorithm,spectral constraint algorithm and U-Net algorithm,the proposed CIFN-based algorithm exhibited the lowest mean absolute error(MAE)and the highest structural similarity(SSIM)when used to image different lesion targets,which accurately reconstructed the distribution of lesion targets and gained high imaging stability under common noise levels.Conclusion The proposed CIFN-based imaging algorithm obtains high imaging quality on a cranial simulation model and reconstruction results close to the real model distribution,which provides algorithmic support for subsequent clinical studies on electrical impedance imaging.[Chinese Medical Equipment Journal,2025,46(6):1-6]

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