1.Effect of Anmeidan on Cognitive Function and Metabolic Profiling in Insomnia Model Rats Based on Untargeted Metabolomics
Feizhou LI ; Bo XU ; Zijing YE ; Lianyu LI ; Andong ZHANG ; Ping WANG ; Linlin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):54-64
ObjectiveTo elucidate the potential mechanisms by which the classic prescription Anmeidan alleviates cognitive impairment in insomnia model rats through metabolic profiling. MethodsA total of 60 SD rats were randomly divided into six groups: blank group, model group, low-, medium-, and high-dose Anmeidan groups, and the Suvorexant group, with 10 rats in each group. Except for the blank group, the insomnia model was established in all other groups via intraperitoneal injection of para-chlorophenylalanine. The Suvorexant group was administered Suvorexant solution (30 mg·kg-1·d-1) by gavage, while the low-, medium-, and high-dose Anmeidan groups received Anmeidan decoction (4.55, 9.09, 18.18 g·kg-1·d-1) by gavage. The blank group received an equivalent volume of normal saline. The open field test was used to assess spatial exploration and anxiety/depressive-like behaviors in rats. Serum levels of epidermal growth factor (EGF), brain-derived neurotrophic factor (BDNF), and vasoactive intestinal peptide (VIP) were measured using enzyme-linked immunosorbent assay (ELISA). Untargeted metabolomics was employed to identify differential metabolites in rat serum, and systematic biological methods were applied to analyze the potential targets and pathways of Anmeidan. ResultsCompared to the blank group, the model group exhibited significant reductions in total distance traveled, average speed, number of entries into the central area, time spent in the central area, and frequency of upright events (P<0.01), along with significant decreases in VIP, EGF, and BDNF levels (P<0.05,P<0.01). A total of 100 differential metabolites were identified between the model and blank groups. Compared to the model group, the low-, medium-, and high-dose Anmeidan groups showed significant increases in total distance traveled, average speed, number of entries into the central area, time spent in the central area, and frequency of upright events (P<0.05,P<0.01), as well as a significant increase in VIP levels (P<0.05,P<0.01). Anmeidan significantly reversed abnormal changes in 67 metabolites compared to the model group. A combined analysis identified 134 potential targets of Anmeidan, with network topology analysis suggesting that Caspase-3, B-cell lymphoma 2 (Bcl-2), nuclear transcription factor-κB (NF-κB), interleukin-1β (IL-1β), interleukin-2 (IL-2), matrix metalloproteinase-9 (MMP-9), and Toll-like receptor 4 (TLR4), among others, may serve as key targets of Anmeidan. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed major enriched pathways, including the cyclic adenosine monophosphate (cAMP) signaling pathway, hypoxia inducible factor-1 (HIF-1) signaling pathway, and IL-17 signaling pathway. ConclusionThis study demonstrates that Anmeidan can recalibrate abnormal metabolic profiles in insomnia model rats to mitigate cognitive impairment, with its mechanisms of action potentially involving the regulation of immune-inflammatory responses, energy metabolism, and apoptosis-related pathways.
2.Signals mining and analysis of deucravacitinib adverse drug events based on FAERS database
Ye HU ; Qineng GONG ; Linlin ZHANG ; Aming WANG ; Wang QI ; Yang MIAO
Chinese Journal of Pharmacoepidemiology 2025;34(4):419-427
Objective To mine adverse drug event(ADE)signals of deucravacitinib,and to guide its rational clinical use.Methods ADE reports reported to the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database from the third quarter of 2022 to the third quarter of 2024 were collected,ADE reports with deucravacitinib as the primary suspect drug were selected for analysis.ADE signals were identified using reporting adds ratios method and Bayesian confidence propagation neural networks method.Results A total of 1,777 ADE reports were collected involving 3,258 ADEs.Sixty-two ADE signals were identified,spanning 14 system-organ classifications.The top five ADE signals based on the number of reported cases were acne,oral ulcers,folliculitis,urticaria,and oral pain.The top five ADE signals based on signal intensity were cystic acne,hepatitis A,acne vulgaris,pustular acne,and folliculitis.ADE signals such as pigmenturia,hepatitis A,and gingival swelling were not included in the drug instructions.The median duration of ADEs associated with deucravacitinib was 22 days,with 58.33%occurring within the first month of treatment.Women may have a higher risk of developing acne than men.Conclusions When using deutericolaxitinib,healthcare professionals should focus on skin and subcutaneous tissue disorders,gastrointestinal system disorders,and infections and infestations to monitor the occurrence of acne in female patients.The latent ADEs that are not mentioned in the instructions should be remained vigilant to ensure safe drug use.
3.Study on the effect of intelligent lower limb rehabilitation robot assisted walking training on the walking function in patients with hemineglect after stroke
Lei CAO ; Linlin YE ; Xiaolong YANG
Chinese Journal of Rehabilitation Medicine 2025;40(9):1308-1313
Objective:To explore whether gait training facilitated by an intelligent lower limb rehabilitation robot can en-hance the walking capabilities of post-stroke patients with hemineglect.Method:A total of forty patients,who had suffered from hemilateral neglect post-stroke,were randomly as-signed to either a control group or an experimental group,with twenty individuals in each.All patients re-ceived conventional pharmacotherapy,repetitive transcranial magnetic stimulation(rTMS),and standard rehabili-tation training.Additionally,the experimental group underwent robot-assisted gait training,whereas the control group was engaged in traditional walking training.Parameters such as hemineglect symptom scores,Fugl-Mey-er assessment for lower extremity(FMA-LE)scores,and various gait metrics(including stride speed,stride length time,stride frequency,stride length time disparity,and impact difference)were evaluated and com-pared between both groups pre-and post-treatment.Result:Initially,no significant disparities were observed in the baseline data of the two groups(all P>0.05).Subsequently,improvements in line segmentation,line bisecting,and star cancellation test scores were noted in both groups post-treatment(all P<0.05).Moreover,the post-treatment FMA-LE scores exhibited a signifi-cant enhancement compared to the pre-treatment scores(all P<0.01),with the experimental group demonstrat-ing a more pronounced improvement(P<0.01).Furthermore,post-treatment assessments indicated notable ad-vancements in walking speed,stride length time,stride frequency,stride length time variance,and impact dif-ference in both groups(all P<0.01),with the experimental group showing superior progress(P<0.01).Conclusion:The findings suggest that gait training using an intelligent lower limb rehabilitation robot not only ameliorates hemineglect symptoms but also significantly improves the walking abilities of stroke patients afflict-ed with hemineglect.
4.Characterization of cortical morphology and structural covariance network features in post-stroke patients with visuospatial neglect
Wanying ZHAO ; Lei CAO ; Weiqun SONG ; Linlin YE
Chinese Journal of Cerebrovascular Diseases 2025;22(7):474-486
Objective To investigate cortical morphological changes and structural covariance network(SCN)topological features in patients with visuospatial neglect(VSN)after stroke.Methods A retrospective analysis was conducted on acute stroke patients admitted consecutively to the Department of Rehabilitation Medicine,Xuanwu Hospital,Capital Medical University,from December 2023 to February 2025.General and clinical data were collected and compared,including age,sex,stroke type(hemorrhagic or ischemic),and time from stroke onset to first brain MRI.All patients were assessed for VSN using the line bisection task,line cancellation test,and star cancellation test.Patients with VSN were assigned to the VSN group,and those without VSN to the non-VSN group.Brain MRI was used to collect patients' brain structural images.T1-weighted MRI data were processed using Freesurfer for whole-brain segmentation.Based on the Desikan-Killiany atlas,the cortex was parcellated into 68 regions per hemisphere,total intracranial volume and cortical parameters were extracted,including cortical area(CA),mean cortical curvature(CC),cortical thickness(CT),and cortical volume(CV).A region-specific asymmetry index(AI)was calculated for cortical parameters of each brain regions using(left-right)/(left+right)to assess cortical lateralization.Analyze the SCN of each cortical parameters through covariance matrix to reflect covariation pattern of each brain region's structural morphological alternations.SCN were constructed separately for each cortical parameter based on inter-regional Pearson correlation coefficients(absolute values),with intracranial volume,age,and sex controlled via linear regression.The resulting 68×68 SCN matrices were transformed into binary networks across a sparsity range of 0.1 to 0.4(in 0.01 steps),and graph theoretical analysis were performed.Permutation tests were used to compare the global and local graph theoretical metrics of cortical SCN under each cortical parameters with different sparsity.Global metrics included clustering coefficient,path length,small-worldness parameters(normalized clustering coefficient[Gamma],normalized path length[Lambda],and small-world index[Sigma]),global efficiency,and average local efficiency.Local metrics included nodal degree,betweenness centrality,and nodal efficiency.Results(1)A total of 109 acute stroke patients were included(81 males,28 females,aged 30-80 years,mean[64±9]years),with 54 in the VSN group and 55 in the non-VSN group.No significant differences were found in age,sex,stroke type,or time from stroke onset to MRI between two groups(all P>0.05).(2)Comparison of cortical features(of different brain regions)between two groups showed significantly larger CA in the right insular surface area in the VSN group(2 466.50[2 143.75,2 662.50]mm2 vs.2 128.00[1 961.00,2 479.00)]mm2,P=0.037).No significant differences were observed in other regions or metrics(all P>0.05).The VSN group has significantly lower AI values for CT in the right isthmus cingulate gyrus(-0.01[-0.05,0.03]vs.0.02[-0.01,0.06],P=0.028)and postcentral gyrus(-0.02[-0.04,0.00]vs.0.00[-0.02,0.02],P=0.026).No significant AI differences were observed in other regions or metrics(all P>0.05).(3)For global network metrics:in the CA-based VSN,compared with the non-VSN group,Sigma values were significantly higher in the VSN group across multiple sparsity thresholds and at the average sparsity level(P<0.01).In the CT-based SCN,Lambda values were significantly higher in the VSN group at most sparsity thresholds and at the average level(P=0.004).In the CC-based SCN,clustering coefficient and average local efficiency were significantly lower in the VSN group across most sparsity thresholds and average sparsity(P<0.01).No significant differences were found in global metrics within the CV-based SCN.(4)For local metrics:in the CV-based SCN,compared with the non-VSN group,the VSN group showed significantly lower nodal efficiency in the left inferior temporal gyrus at most sparsity thresholds and at the average level(0.35[0.29,0.50]vs.0.65[0.51,0.72],P<0.01).No significant differences in local metrics were observed in other SCN between the two groups.Conclusions Patients with VSN exhibit abnormal cortical morphology and SCN topology,characterized by reduced overall integration efficiency and weakened local connectivity,alongside enhanced small-worldness and possible compensatory reorganization.The conclusions of this study require further validation in multicenter,large-scale,prospective studies.
5.Signals mining and analysis of deucravacitinib adverse drug events based on FAERS database
Ye HU ; Qineng GONG ; Linlin ZHANG ; Aming WANG ; Wang QI ; Yang MIAO
Chinese Journal of Pharmacoepidemiology 2025;34(4):419-427
Objective To mine adverse drug event(ADE)signals of deucravacitinib,and to guide its rational clinical use.Methods ADE reports reported to the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database from the third quarter of 2022 to the third quarter of 2024 were collected,ADE reports with deucravacitinib as the primary suspect drug were selected for analysis.ADE signals were identified using reporting adds ratios method and Bayesian confidence propagation neural networks method.Results A total of 1,777 ADE reports were collected involving 3,258 ADEs.Sixty-two ADE signals were identified,spanning 14 system-organ classifications.The top five ADE signals based on the number of reported cases were acne,oral ulcers,folliculitis,urticaria,and oral pain.The top five ADE signals based on signal intensity were cystic acne,hepatitis A,acne vulgaris,pustular acne,and folliculitis.ADE signals such as pigmenturia,hepatitis A,and gingival swelling were not included in the drug instructions.The median duration of ADEs associated with deucravacitinib was 22 days,with 58.33%occurring within the first month of treatment.Women may have a higher risk of developing acne than men.Conclusions When using deutericolaxitinib,healthcare professionals should focus on skin and subcutaneous tissue disorders,gastrointestinal system disorders,and infections and infestations to monitor the occurrence of acne in female patients.The latent ADEs that are not mentioned in the instructions should be remained vigilant to ensure safe drug use.
6.Study on the effect of intelligent lower limb rehabilitation robot assisted walking training on the walking function in patients with hemineglect after stroke
Lei CAO ; Linlin YE ; Xiaolong YANG
Chinese Journal of Rehabilitation Medicine 2025;40(9):1308-1313
Objective:To explore whether gait training facilitated by an intelligent lower limb rehabilitation robot can en-hance the walking capabilities of post-stroke patients with hemineglect.Method:A total of forty patients,who had suffered from hemilateral neglect post-stroke,were randomly as-signed to either a control group or an experimental group,with twenty individuals in each.All patients re-ceived conventional pharmacotherapy,repetitive transcranial magnetic stimulation(rTMS),and standard rehabili-tation training.Additionally,the experimental group underwent robot-assisted gait training,whereas the control group was engaged in traditional walking training.Parameters such as hemineglect symptom scores,Fugl-Mey-er assessment for lower extremity(FMA-LE)scores,and various gait metrics(including stride speed,stride length time,stride frequency,stride length time disparity,and impact difference)were evaluated and com-pared between both groups pre-and post-treatment.Result:Initially,no significant disparities were observed in the baseline data of the two groups(all P>0.05).Subsequently,improvements in line segmentation,line bisecting,and star cancellation test scores were noted in both groups post-treatment(all P<0.05).Moreover,the post-treatment FMA-LE scores exhibited a signifi-cant enhancement compared to the pre-treatment scores(all P<0.01),with the experimental group demonstrat-ing a more pronounced improvement(P<0.01).Furthermore,post-treatment assessments indicated notable ad-vancements in walking speed,stride length time,stride frequency,stride length time variance,and impact dif-ference in both groups(all P<0.01),with the experimental group showing superior progress(P<0.01).Conclusion:The findings suggest that gait training using an intelligent lower limb rehabilitation robot not only ameliorates hemineglect symptoms but also significantly improves the walking abilities of stroke patients afflict-ed with hemineglect.
7.Characterization of cortical morphology and structural covariance network features in post-stroke patients with visuospatial neglect
Wanying ZHAO ; Lei CAO ; Weiqun SONG ; Linlin YE
Chinese Journal of Cerebrovascular Diseases 2025;22(7):474-486
Objective To investigate cortical morphological changes and structural covariance network(SCN)topological features in patients with visuospatial neglect(VSN)after stroke.Methods A retrospective analysis was conducted on acute stroke patients admitted consecutively to the Department of Rehabilitation Medicine,Xuanwu Hospital,Capital Medical University,from December 2023 to February 2025.General and clinical data were collected and compared,including age,sex,stroke type(hemorrhagic or ischemic),and time from stroke onset to first brain MRI.All patients were assessed for VSN using the line bisection task,line cancellation test,and star cancellation test.Patients with VSN were assigned to the VSN group,and those without VSN to the non-VSN group.Brain MRI was used to collect patients' brain structural images.T1-weighted MRI data were processed using Freesurfer for whole-brain segmentation.Based on the Desikan-Killiany atlas,the cortex was parcellated into 68 regions per hemisphere,total intracranial volume and cortical parameters were extracted,including cortical area(CA),mean cortical curvature(CC),cortical thickness(CT),and cortical volume(CV).A region-specific asymmetry index(AI)was calculated for cortical parameters of each brain regions using(left-right)/(left+right)to assess cortical lateralization.Analyze the SCN of each cortical parameters through covariance matrix to reflect covariation pattern of each brain region's structural morphological alternations.SCN were constructed separately for each cortical parameter based on inter-regional Pearson correlation coefficients(absolute values),with intracranial volume,age,and sex controlled via linear regression.The resulting 68×68 SCN matrices were transformed into binary networks across a sparsity range of 0.1 to 0.4(in 0.01 steps),and graph theoretical analysis were performed.Permutation tests were used to compare the global and local graph theoretical metrics of cortical SCN under each cortical parameters with different sparsity.Global metrics included clustering coefficient,path length,small-worldness parameters(normalized clustering coefficient[Gamma],normalized path length[Lambda],and small-world index[Sigma]),global efficiency,and average local efficiency.Local metrics included nodal degree,betweenness centrality,and nodal efficiency.Results(1)A total of 109 acute stroke patients were included(81 males,28 females,aged 30-80 years,mean[64±9]years),with 54 in the VSN group and 55 in the non-VSN group.No significant differences were found in age,sex,stroke type,or time from stroke onset to MRI between two groups(all P>0.05).(2)Comparison of cortical features(of different brain regions)between two groups showed significantly larger CA in the right insular surface area in the VSN group(2 466.50[2 143.75,2 662.50]mm2 vs.2 128.00[1 961.00,2 479.00)]mm2,P=0.037).No significant differences were observed in other regions or metrics(all P>0.05).The VSN group has significantly lower AI values for CT in the right isthmus cingulate gyrus(-0.01[-0.05,0.03]vs.0.02[-0.01,0.06],P=0.028)and postcentral gyrus(-0.02[-0.04,0.00]vs.0.00[-0.02,0.02],P=0.026).No significant AI differences were observed in other regions or metrics(all P>0.05).(3)For global network metrics:in the CA-based VSN,compared with the non-VSN group,Sigma values were significantly higher in the VSN group across multiple sparsity thresholds and at the average sparsity level(P<0.01).In the CT-based SCN,Lambda values were significantly higher in the VSN group at most sparsity thresholds and at the average level(P=0.004).In the CC-based SCN,clustering coefficient and average local efficiency were significantly lower in the VSN group across most sparsity thresholds and average sparsity(P<0.01).No significant differences were found in global metrics within the CV-based SCN.(4)For local metrics:in the CV-based SCN,compared with the non-VSN group,the VSN group showed significantly lower nodal efficiency in the left inferior temporal gyrus at most sparsity thresholds and at the average level(0.35[0.29,0.50]vs.0.65[0.51,0.72],P<0.01).No significant differences in local metrics were observed in other SCN between the two groups.Conclusions Patients with VSN exhibit abnormal cortical morphology and SCN topology,characterized by reduced overall integration efficiency and weakened local connectivity,alongside enhanced small-worldness and possible compensatory reorganization.The conclusions of this study require further validation in multicenter,large-scale,prospective studies.
8.Protective effect of Lonicerae japonicae flos extract against doxorubicin-induced liver injury in mice
Yuming ZHANG ; Shicheng XIA ; Linlin ZHANG ; Mengxi CHEN ; Xiaojing LIU ; Qin GAO ; Hongwei YE
Journal of Southern Medical University 2024;44(8):1571-1581
Objective To explore the mechanism underlying the protective effect of Lonicerae japonicae flos(LJF)extract against doxorubicin(DOX)-induced liver injury in mice.Methods Network pharmacology methods were used to obtain the intersection genes between LJF targets and disease targets,based on which the protein-protein interaction(PPI)network was constructed using STRING database for screening the core targets using Cytoscape software.DAVID database was used for bioinformatics analysis,and the core components and core targets were verified using molecular docking study.In a mouse model of DOX-induced liver injury,the effect of LJF extract on liver pathologies,serum levels of ALT and AST,and hepatic expressions of HYP,ROS,TNF-α,IL-6,COL-IV and P53 proteins were evaluated using HE and Masson staining,ELISA,and Western blotting.Results We identified 12 core targets from 43 intersection genes involving cancer pathway,IL-17 signaling pathway,and TNF signaling pathways.Molecular docking study suggested that 10 core components of LJF could bind to different core targets.The mice with DOX-induced liver injury showed elevated serum AST and ALT levels with obvious liver injury and fibrosis,increased ROS content,and enhanced expressions of TNF-α,IL-6,HYP,COL-IV and P53 proteins in the liver tissue.All these changes in the mouse models were significantly alleviated by treatment with LJF extract,suggesting obviously lowered levels of oxidative stress,inflammation and fibrosis in the liver tissues.Conclusion LJF extract is capable of alleviating DOX-induced liver injury in mice by downregulating Trp53,TNF and IL-6 to reduce liver oxidative stress,inflammation and fibrosis.
9.Epidemiological characteristics of human respiratory syncytial virus in Hubei Province from 2016 to 2023
Qiangling YIN ; Xiao YU ; Xiang LI ; Bin FANG ; Xiaolu ZHANG ; Mingwei PENG ; Guojun YE ; Linlin LIU
Chinese Journal of Preventive Medicine 2024;58(8):1129-1134
Objective:To analyze the epidemiological characteristics of human respiratory syncytial virus (HRSV) in patients with acute respiratory infection (ARIs) in sentinel hospitals of the Hubei influenza surveillance network from 2016 to 2023.Methods:ARIs samples [including influenza-like cases (ILI) and severe acute respiratory infection (SARI)] were collected from influenza surveillance sentinel hospitals in Hubei Province from 2016 to 2023, and case information was collected. HRSV virus nucleic acid typing was performed by fluorescence quantitative PCR method, and the data were collated, plotted and analyzed.Results:From 2016 to 2023, 12 779 cases of ILI and 9 166 cases of SARI were collected. The positive rate of HRSV was the highest in<5 years of age group [15.77% (168/1 065)], among which the positive rate was the highest in 2 to 5 years of age group of ILI cases [13.60% (31/228)], and the positive rate was the highest in 0 to 2 years of age group of SARI cases [25.97% (60/231)] (all P values<0.001). The positive rate of HRSV in SARI cases was 2.31%-25.97%, higher than that in ILI cases (0-13.60%) ( P=0.016). HRSV was prevalent in autumn and winter from 2016 to 2020 and in spring in 2023. Alternating epidemics of HRSV virus type A and B in Hubei Province from 2016 to 2023 (dominant epidemics of type B in 2016 and 2020; dominant epidemics of type A in 2017-2019 and 2023). Conclusion:SARI and ILI patients under five years old are the main infection groups of HRSV. The seasonal prevalence characteristics of HRSV in Hubei Province from 2016 to 2023 shift from autumn and winter to spring.
10.Epidemiological characteristics of human respiratory syncytial virus in Hubei Province from 2016 to 2023
Qiangling YIN ; Xiao YU ; Xiang LI ; Bin FANG ; Xiaolu ZHANG ; Mingwei PENG ; Guojun YE ; Linlin LIU
Chinese Journal of Preventive Medicine 2024;58(8):1129-1134
Objective:To analyze the epidemiological characteristics of human respiratory syncytial virus (HRSV) in patients with acute respiratory infection (ARIs) in sentinel hospitals of the Hubei influenza surveillance network from 2016 to 2023.Methods:ARIs samples [including influenza-like cases (ILI) and severe acute respiratory infection (SARI)] were collected from influenza surveillance sentinel hospitals in Hubei Province from 2016 to 2023, and case information was collected. HRSV virus nucleic acid typing was performed by fluorescence quantitative PCR method, and the data were collated, plotted and analyzed.Results:From 2016 to 2023, 12 779 cases of ILI and 9 166 cases of SARI were collected. The positive rate of HRSV was the highest in<5 years of age group [15.77% (168/1 065)], among which the positive rate was the highest in 2 to 5 years of age group of ILI cases [13.60% (31/228)], and the positive rate was the highest in 0 to 2 years of age group of SARI cases [25.97% (60/231)] (all P values<0.001). The positive rate of HRSV in SARI cases was 2.31%-25.97%, higher than that in ILI cases (0-13.60%) ( P=0.016). HRSV was prevalent in autumn and winter from 2016 to 2020 and in spring in 2023. Alternating epidemics of HRSV virus type A and B in Hubei Province from 2016 to 2023 (dominant epidemics of type B in 2016 and 2020; dominant epidemics of type A in 2017-2019 and 2023). Conclusion:SARI and ILI patients under five years old are the main infection groups of HRSV. The seasonal prevalence characteristics of HRSV in Hubei Province from 2016 to 2023 shift from autumn and winter to spring.

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