1.Characteristics of brain glymphatic system changes in patients with amnestic mild cognitive impairment based on perivascular spaces and DTI-ALPS index assessment
Xiaoqin CHENG ; Guoqiang FEI ; Shen ZHAO ; Rui HUA ; Feng SHI ; Xiaoli PAN ; Ziyi HE ; Sirui LIU
Chinese Journal of Clinical Medicine 2026;33(3):479-485
Objective To explore the characteristics and correlation between perivascular spaces (PVS) and diffusion tensor image analysis along perivascular spaces (DTI-ALPS) index in patients with amnestic mild cognitive impairment (aMCI). Methods A retrospective study was conducted on a total of 118 participants, including cognitive normal (CN) healthy controls and aMCI patients, recruited from the Department of Neurology, Zhongshan Hospital, Fudan University from September 2020 to September 2022. All participants underwent structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). An automatic segmentation algorithm was used to quantify PVS metrics in the brain, and DTI-ALPS index was calculated based on DTI. Differences in DTI-ALPS index and PVS metrics between the CN and aMCI groups were compared. Multivariate logistic regression was used to identify independent factors influencing aMCI. Correlation analysis was performed to assess relationships among DTI-ALPS index, PVS metrics, and cognitive scores. Results A total of 80 CN healthy controls and 38 aMCI patients were included. The DTI-ALPS index was significantly lower in the aMCI group compared with the CN group (1.28±0.18 vs 1.37±0.21, P=0.018), while differences in PVS metrics between groups were not statistically significant. Multivariate logistic regression analysis indicated that DTI-ALPS index was an independent factor affecting aMCI (OR=0.097, 95%CI 0.011–0.833, P=0.033). Correlation analysis revealed a positive relationship between DTI-ALPS index and MMSE score (r=0.210, P=0.023) as well as PVS length in the centrum semiovale (r=0.216, P=0.019). Conclusions The DTI-ALPS index may serve as an imaging biomarker for identifying early cognitive impairment, and patients with aMCI exhibit abnormal DTI-ALPS indices, suggesting that brain glymphatic system dysfunction may occur prior to morphological changes.
2.Dual Targeting of TBK1 and JAK-STAT1 Pathways by (-)-epigallocatechin-3-gallate Suppresses Type I Interferon-driven Inflammation
Liang LI ; Qi-Huan SHENG ; Huan LIU ; Wen-Hao YANG ; Jia-Lin SHI ; Ying-Jie SUN ; Rui JING ; Wei-Hua MAI ; Zhi-Min LI ; Xiao-Li XIE
Progress in Biochemistry and Biophysics 2026;53(7):1969-1983
ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.
3.Study on the differences in node strength of white matter networks in patients with depressive disorder and bipolar disorder
Haiyan LIU ; Jiabo SHI ; Lingling HUA ; Rui YAN ; Hao TANG ; Zhijian YAO
Chinese Journal of Nervous and Mental Diseases 2025;51(6):321-326
Objective To compare the node strength in white matter networks between depressive disorder and bipolar depression patients,analyze structural connectivity impairments across brain regions,and assess their diagnostic utility.Methods This longitudinal study initially enrolled 91 patients with a baseline diagnosis of depressive episode.All subjects underwent diffusion tensor imaging at recruitment and white matter structural weighted networks were constructed using deterministic fiber tracking.After≥9 years of naturalistic follow-up,23 patients who maintained a diagnosis of major depressive disorder(MDD group)and 18 patients who maintained a diagnosis of bipolar disorder(BD group),while 30 demographically matched healthy controls(HC group)were included for comparison.The differences in nodal connection strength within the brain white matter networks among the three groups were compared.Furthermore,the receiver operator characteristic(ROC)curve was utilized to evaluate the diagnostic value of the differential brain regions in distinguishing between MDD and BD.Results In the left anterior cingulate gyrus,the node strength was lower in the BD than in the MDD group(3.89±0.76 vs.4.74±0.60).However,the node strength in the right caudate nucleus(4.94±1.26 vs.3.46±0.99)and right globus pallidus(1.98±0.67 vs.1.25±0.29)was higher in the BD than in the MDD group(P<0.01,FWE-corrected).The combined connectivity strengths of three brain regions—the left anterior cingulate gyrus,right caudate nucleus and right globus pallidus—were used to differentiate between MDD and BD,and an ROC curve was plotted,with an area under the curve(AUC)of 0.95(95%CI:0.91~0.99;P<0.001).The sensitivity and the specificity were 0.89 and 0.87,respectively.Conclusion The differences in node strength between patient groups may serve as a potential neuroimaging biomarker.Integration of node connectivity strengths from these differential brain regions can achieve superior discrimination accuracy.
4.Effects of TREM2 on synaptic plasticity induced by cocaine addiction
Rui-ke XU ; Zhi-wen WANG ; Jiao-jiao OUYANG ; Qi DU ; Li-hua LI ; Shi-jun HONG ; Yan-xia PENG ; Gen-meng YANG
Chinese Pharmacological Bulletin 2025;41(12):2341-2347
Aim To investigate the role of triggering receptor expressed on myeloidcells 2(TREM2)in syn-aptic plasticity induced by cocaine addiction.Methods C57BL/6J mice and Trem2 knockout mice were uti-lized in this study to evaluate the alterations in postsyn-aptic density protein 95(PSD-95)and synapsin 1(SYN1)within the cortex and hippocampus of co-caine-addicted mice by using immunological tech-niques.Results HE staining and Nissl staining showed increased neuronal damage in the hippocampus and cortex of mice after cocaine addiction.The results of immunohistochemistry and fluorescence of PSD-95 and SYN1 were consistent with the expression trend of Western blot.In the wild type mouse model,the ex-pression level of PSD-95 in the hippocampus and cortex was lower than that in the saline group,and the ex-pression of SYN1 was higher than that in the saline group.In the knockout mouse model,the expression levels of PSD-95 and SYN1 in the hippocampus and cortex were significantly higher than those in the saline group after cocaine addiction.The expression levels of PSD-95 and SYN1 in the hippocampus and cortex of cocaine knockout mice were higher than those of co-caine wild type mice.Conclusion Cocaine addiction can change the synaptic plasticity,and TREM2 plays a regulatory role in the synaptic plasticity of hippocampus and cortex in mice with cocaine injury.TREM2 is ex-pected to be a new target for studying the mechanism of cocaine addiction.
5.The correlation between functional level and the cost of stroke rehabilitation during hospitalization
Qianqian SUN ; Yulin SHI ; Hua TANG ; Rui LI ; Suchen ZHAO ; Luwen ZHANG ; Yumeng FENG ; Dengfeng WAN ; Tiebin YAN
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(4):325-330
Objective:To explore the significance of any correlation between the cost of the rehabilitation provided to stroke survivors during their hospitalization and the functional levels attained, and to analyze factors influencing that correlation.Methods:The International Classification of Functioning, Disability and Health Rehabilitation Set (ICF-RS) was used to evaluate the functioning of 304 stroke survivors on their days of hospital admission and discharge, as well as on their 10th day in hospital. The cost of their rehabilitation was computed, and demographic and clinical data were collected. A generalized estimation equation was used to analyze the changes in dysfunction with time and its risk factors. The relationship between functional levels and rehabilitation cost and its influencing factors were analyzed.Results:Length of stay, age≥60 and hemorrhagic stroke were significant risk factors for greater dysfunction among the stroke survivors. On the 10th day in hospital and the day before discharge (the 18th day), the frequency of severe dysfunction had decreased. The significant predictors of increased cost were severe or moderate dysfunction, the stage of stroke (sub-acute stage), and non-first rehabilitation.Conclusion:Functional level is a useful predictor of rehabilitation cost. It is influenced by the stage of stroke and non-first rehabilitation.
6.Exploring the Protective Effect and Mechanism of Rougan Tongluo Decoction on Ischemic Stroke Induced Motor Disorder Rats Based on NLRP3/GSDMD/Aspase-1 Pathway
Ming-yue YANG ; Le XIE ; Yao XIE ; Rui FANG ; Shi-liang WANG ; Shan-shan ZENG ; Da-hua WU
Progress in Modern Biomedicine 2025;25(20):3201-3210
Objective:To explore the protective effect and mechanism of Rougan Tongluo Decoction on ischemic stroke induced motor disorder rats based on NOD-like receptor thermal protein domain associated protein 3(NLRP3)/Gasdermin D(GSDMD)/Cysteinyl aspartate specific proteinase 1(Caspase-1)pathway.Methods:Establishing a rat model of ischemic stroke with motor disorders using the modified suture method.The rats were randomly divided into model control group,Rougan Tongluo Decoction low,medium and high dose groups and butylphthalide soft capsule group,with 10 rats in each group,Another 10 rats were selected as sham surgery group.After 28 days of administration,the neurological function of rats in each group was evaluated by the Zea-Longa scoring method;The forelimb grasping force of rats in each group was detected by grip tester;The coordination ability of rats was evaluated by rat-mouse rotarod instrument;The expression of NLRP3,GSDMD,Caspase-1 protein and Interleukin-1β(IL-1β)was detected by immunohistochemistry.Results:The NLRP3,Caspase-1,GSDMD protein and IL-1β expression Zea-Longa score in the cerebral cortex of the model control group were significantly higher than those in sham surgery group,the forelimb grasping force was lower than that in sham surgery group,and the latency period for turning the baton was shorter than that in sham surgery group(P<0.05).The Zeba-Longa score,NLRP3,Caspase-1,GSDMD protein and IL-1 β expression in the cerebral cortex the butylphthalide soft capsule group,low dose,medium dose,high dose Rougan Tongluo decoction group were lower than those in model control group,the forelimb grasping force was higher than that in model control group,and the latency period for turning the baton was longer than that in model control group(P<0.05).Conclusion:Rougan Tongluo Decoction may alleviate inflammatory response by regulating the NLRP3/Caspase-1/GSDMD signaling pathway to improve neurological function and motor ability in ischemic stroke induced motor disorder rats.
7.The correlation between functional level and the cost of stroke rehabilitation during hospitalization
Qianqian SUN ; Yulin SHI ; Hua TANG ; Rui LI ; Suchen ZHAO ; Luwen ZHANG ; Yumeng FENG ; Dengfeng WAN ; Tiebin YAN
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(4):325-330
Objective:To explore the significance of any correlation between the cost of the rehabilitation provided to stroke survivors during their hospitalization and the functional levels attained, and to analyze factors influencing that correlation.Methods:The International Classification of Functioning, Disability and Health Rehabilitation Set (ICF-RS) was used to evaluate the functioning of 304 stroke survivors on their days of hospital admission and discharge, as well as on their 10th day in hospital. The cost of their rehabilitation was computed, and demographic and clinical data were collected. A generalized estimation equation was used to analyze the changes in dysfunction with time and its risk factors. The relationship between functional levels and rehabilitation cost and its influencing factors were analyzed.Results:Length of stay, age≥60 and hemorrhagic stroke were significant risk factors for greater dysfunction among the stroke survivors. On the 10th day in hospital and the day before discharge (the 18th day), the frequency of severe dysfunction had decreased. The significant predictors of increased cost were severe or moderate dysfunction, the stage of stroke (sub-acute stage), and non-first rehabilitation.Conclusion:Functional level is a useful predictor of rehabilitation cost. It is influenced by the stage of stroke and non-first rehabilitation.
8.Study on the differences in node strength of white matter networks in patients with depressive disorder and bipolar disorder
Haiyan LIU ; Jiabo SHI ; Lingling HUA ; Rui YAN ; Hao TANG ; Zhijian YAO
Chinese Journal of Nervous and Mental Diseases 2025;51(6):321-326
Objective To compare the node strength in white matter networks between depressive disorder and bipolar depression patients,analyze structural connectivity impairments across brain regions,and assess their diagnostic utility.Methods This longitudinal study initially enrolled 91 patients with a baseline diagnosis of depressive episode.All subjects underwent diffusion tensor imaging at recruitment and white matter structural weighted networks were constructed using deterministic fiber tracking.After≥9 years of naturalistic follow-up,23 patients who maintained a diagnosis of major depressive disorder(MDD group)and 18 patients who maintained a diagnosis of bipolar disorder(BD group),while 30 demographically matched healthy controls(HC group)were included for comparison.The differences in nodal connection strength within the brain white matter networks among the three groups were compared.Furthermore,the receiver operator characteristic(ROC)curve was utilized to evaluate the diagnostic value of the differential brain regions in distinguishing between MDD and BD.Results In the left anterior cingulate gyrus,the node strength was lower in the BD than in the MDD group(3.89±0.76 vs.4.74±0.60).However,the node strength in the right caudate nucleus(4.94±1.26 vs.3.46±0.99)and right globus pallidus(1.98±0.67 vs.1.25±0.29)was higher in the BD than in the MDD group(P<0.01,FWE-corrected).The combined connectivity strengths of three brain regions—the left anterior cingulate gyrus,right caudate nucleus and right globus pallidus—were used to differentiate between MDD and BD,and an ROC curve was plotted,with an area under the curve(AUC)of 0.95(95%CI:0.91~0.99;P<0.001).The sensitivity and the specificity were 0.89 and 0.87,respectively.Conclusion The differences in node strength between patient groups may serve as a potential neuroimaging biomarker.Integration of node connectivity strengths from these differential brain regions can achieve superior discrimination accuracy.
9.ADAMS-based dynamic simulation analysis of surgical robot for pedicle screw placement
Li-hua YAO ; Zhi-ming CHE ; Xiang-rui MENG ; Shi-yang WU ; Yi-xun FANG
Chinese Medical Equipment Journal 2025;46(8):32-37
Objective To carry out a dynamic simulation analysis on the surgical process of the surgical robot for pedicle screw placement so as to enhance the safety of the procedure.Methods Firstly,the process of pedicle screw placement were analyzed to determine the three typical force conditions during pedicle screw track drilling including no-load condition,bone layer switching condition and spine dynamic displacement condition.Secondly,a virtual protype model of the surgical robot for pedicle screw placement was constructed with the automated dynamic analysis of mechanical systems(ADAMS).Finally,the dynamic characteristics of the surgical robot were simulated and analyzed with considerations on the three typical force conditions.Results The driving torque of the robot joints was sensitive to the load applied to the end of the opener mechanism under a wide range of operating conditions.Conclusion The surgical robot meets the requirements for pedicle screw placment,and a new idea is provided for enhancing the accuracy of pedicle screw placement.[Chinese Medical Equipment Journal,2025,46(8):32-37]
10.Comparison of chemical constituents in traditional decoction and formula granule decoction of Wendan Decoction
Tan XUE ; Man-wen XU ; Xue-hua FAN ; Feng-yu DONG ; Yan MIAO ; Jia-ning SUN ; Jun-han SHI ; Lu ZHANG ; Jing YAO ; Rui-xin LIU
Chinese Traditional Patent Medicine 2025;47(2):384-394
AIM To compare the chemical constituents in traditional decoction and formula granule decoction of classical famous prescription Wendan Decoction.METHODS The HPLC fingerprints were established,after which the contents of adenosine,synephrine,liquiritin,naringin,hesperidin,6-gingerol and adenosine cyclophosphate were determined,cluster analysis,principal component analysis and multidimensional scaling analysis were adopted in the investigation of component differences,and the equivalent of formula granules was adjusted.RESULTS The similarities of HPLC fingerprints for 10 batches of traditional decoctions were higher than those of HPLC fingerprints for 9 batches of formula granule decoctions(P<0.01).Adenosine,synephrine,liquiritin,hesperidin and cyclic adenosine monophosphate demonstrated higher contents in traditional decoctions than those in formula granule decoctions(P<0.05),6-gingerol displayed lower content than that in the latter produced by manufacturers A,C(P<0.05),which was higher than that in the latter produced by manufacturer B(P<0.01).Various batches of traditional decoctions and formula granule decoctions could be obviously distinguished,adenosine,synephrine and hesperidin exhibited great influences on the classification of principal component analysis,and the quality of formula granule decoctions produced by manufacturer C was closer to that of traditional decoctions.After equivalent correction,the contents of various constituents in formula granule decoctions produced by manufacturers A,C showed no significant differences as compared with those in traditional decoction(P>0.05).CONCLUSION The formula granules of Wendan Decoction from different manufacturers exist quality differences,so the preparation process and extraction process of this preparation should be optimized to improve quality,and equivalent ratio should be adjusted according to actual requirements to ensure its scientific and rational clinical application.

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