1.Effects of nuciferine on neuroinflammation and ferroptosis in mice with chronic hypoperfusion-induced white matter injury
Ting-ting DUAN ; Gui-min JIN ; Yuan-yuan ZHU ; Yu-hao XU ; Yue-feng LI ; Chen QIAO ; Ming YU
Chinese Pharmacological Bulletin 2025;41(10):1931-1940
Aim To explore the effects of nuciferine on cognitive behavior and the underlying mechanisms,white matter injury(WMI),neuroinflammation,and ferroptosis in mice with chronic ischemic WMI.Meth-ods Sixty C57BL/6 mice were divided into a control group,a bilateral common carotid artery stenosis(BCAS)model group,and low/high-dose nuciferine groups(20/40 mg·kg-1).A chronic ischemic WMI model was established using BCAS surgery.Following eight weeks of treatment,cognitive behavior(Y-maze,novel object recognition,Morris water maze),white matter integrity(LFB/MBP staining),microglial acti-vation(Iba-1 immunofluorescence),inflammatory cy-tokines(ELISA for TNF-α,IL-1β,IL-6),ferroptosis markers(Fe2+,ROS,MDA,GSH),mitochondrial ultrastructure(electron microscopy),and protein ex-pression of the PI3K/Akt and NRF2/xCT/GPX4 signa-ling pathways(Western blot)were evaluated.Results Compared with the control group,the BCAS group showed significant cognitive decline(P<0.05),re-duced myelin density,elevated inflammatory cytokines and ferroptosis markers(Fe2+,ROS,MDA),shrunk-en mitochondria,and downregulated PI3K/Akt and NRF2/xCT/GPX4 pathway proteins(P<0.05).Nu-ciferine intervention significantly ameliorated these in-juries in BCAS mice,with the high-dose group exhibi-ting superior effects(P<0.05).Conclusions Nu-ciferine exerts protective effects against chronic ische-mic WMI and cognitive impairment by activating the PI3K/Akt and NRF2/xCT/GPX4 signaling pathways,thereby suppressing neuroinflammation and ferroptosis.
2.Protective effect of stereotactic neuroendoscopic hematoma evacuation on neurological function in hypertensive intracerebral hemorrhage patients
Jie GAO ; Yu YUAN ; Mingyue LI ; Ming ZHANG ; Xu LIU
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(2):202-205
Objective To compare the effects of stereotactic endoscopic hematoma evacuation on elderly patients with hypertensive intracerebral hemorrhage.Methods A total of 220 patients with hypertensive intracerebral hemorrhage in the basal ganglion admitted to our hospital from January 2020 to December 2023 were retrospectively recruited.According to their surgical treat-ment,they were divided into an observation group(stereotactic endoscopic hematoma evacuation,n=100)and a control group(craniotomy hematoma removal surgery,n=120).Postoperative recovery was observed and compared between the two groups.Results There was no significant difference in operation time between the observation group and the control group(94.56±14.75 min vs 94.03±14.50 min,t=0.268,P=0.789).No statistical differences were observed in the NIHSS score before operation between the two groups(P=0.058),but the observation group obtained significantly lower NIHSS scores in 3 and 6 months after surgery(5.90±4.02 vs 9.23±3.47,P=0.000;4.54±2.56 vs 6.50±3.07,P=0.000).There were no significant differences in GOS score and incidence of postoperative complications between the two groups(P>0.05).Conclusion Stereotactic endoscopic hematoma evacuation can improve postoperative neurological function in patients with hypertensive intracerebral hemorrhage in the basal ganglia region.
3.Evodiamine modulation of FOXM1 expression promotes apoptosis in colon cancer resistant cells HCT8/5-FU
Jing MA ; Di-long CHEN ; Yuan-yuan WAN ; Jia-ming HE ; An CHEN ; Yun-ying LI ; Hui-min WANG ; Jing LI
Chinese Pharmacological Bulletin 2025;41(1):35-43
Aim To study the effect of evodiamine(EVO)regulating forkhead box protein Ml(FOXM1)on the proliferation and apoptosis of colorectal cancer-resistant cells HCT8/5-FU.Methods CCK-8 assay and EdU assay were used to detect the effect of EVO on cell proliferation ability.Clone formation assay was employed to detect the effect of EVO on the clone for-mation ability of cells.Flow cytometric counting was applied to detect apoptosis.Western blot was utilized to detect the expression of cellular Bcl-2,Bax,FOXM1,β-catenin,c-MYC,and CyclinD1;Molecular docking was used to explore the EVO-FOXM1 interac-tion.Nude mouse transplant tumor model was estab-lished to validate the effect of EVO on HCT8/5-FU cells in vivo.Results CCK-8 assay showed that EVO inhibited the proliferation of HCT8/5-FU cells in a time-and concentration-dependent manner.EdU assay found that the newly proliferated cells in the EVO-trea-ted group were significantly reduced.The results of the clone formation assay showed that EVO inhibited the clone-forming ability of HCT8/5-FU cells.Flow cyto-metric counting found that apoptosis rate of the cells in the EVO group significantly increased.Western blot showed that FOXM1 and β-catenin were significantly highly expressed in HCT8/5-FU cells,and EVO down-regulated the expression of FOXM1,β-cateniin,c-MYC,CyclinD1,and Bcl-2,and up-regulated the ex-pression of Bax.Molecular docking revealed strong in-teractions between EVO and FOXM1.The in vivo ex-perimental results demonstrated that EVO exerted a substantial inhibitory effect on the growth of subcutane-ously implanted HCT8/5-FU xenograft tumors and regulated the expression of related proteins.HE stai-ning revealed significant nuclear consolidation and fragmentation of tumor cells in the EVO group.Con-clusions The findings suggest that EVO could sup-press the activation of the Wnt signaling pathway through a mechanism involving the downregulation of FOXM1 protein expression,thus inhibiting the prolifer-ation of HCT8/5-FU cells and induce their apoptosis.
4.Hemodynamic disturbance and mTORC1 activation:Unveiling the biomechanical pathogenesis of thoracic aortic aneurysms in Marfan syndrome
Ming-Yuan LIU ; Meili WANG ; Junjun LIU ; An-Qiang SUN ; Chang-Shun HE ; Xin CONAG ; Wei KONG ; Wei LI
Journal of Pharmaceutical Analysis 2025;15(2):459-473
Thoracic aortic aneurysm(TAA)significantly endangers the lives of individuals with Marfan syndrome(MFS),yet the intricacies of their biomechanical origins remain elusive.Our investigation delves into the pivotal role of hemodynamic disturbance in the pathogenesis of TAA,with a particular emphasis on the mechanistic contributions of the mammalian target of rapamycin(mTOR)signaling cascade.We un-covered that activation of the mTOR complex 1(mTORC1)within smooth muscle cells,instigated by the oscillatory wall shear stress(OSS)that stems from disturbed flow(DF),is a catalyst for TAA progression.This revelation was corroborated through both an MFS mouse model(Fbn1+/C1039G)and clinical MFS specimens.Crucially,our research demonstrates a direct linkage between the activation of the mTORC1 pathway and the intensity in OSS.Therapeutic administration of rapamycin suppresses mTORC1 activity,leading to the attenuation of aberrant SMC behavior,reduced inflammatory infiltration,and restoration of extracellular matrix integrity—collectively decelerating TAA advancement in our mouse model.These insights posit the mTORC1 axis as a strategic target for intervention,offering a novel approach to manage TAAs in MFS and potentially pave insights for current treatment paradigms.
5.A case of complex structural variants in the Xq28 region diagnosed by whole genome sequencing.
Yulai YANG ; Chuang LI ; Ming GAO ; Yuan LYU
Chinese Journal of Medical Genetics 2025;42(3):355-359
OBJECTIVE:
To re-analyze a likely pathogenic variant in the Xq28 region identified by copy number variation sequencing (CNV-seq) through whole genome sequencing (WGS).
METHODS:
A fetus found to harbor a duplication in the Xq28 region by CNV-seq at Shengjing Hospital Affiliated to China Medical University in May 2023 was selected as the study subject. WGS was carried out for the fetus and its parents. Bioinformatic software was used to analyze the chromosomal structure and CNVs. Quantitative PCR (qPCR) was applied to determine the expression level of the MECP2 gene. This study has been approved by the Ethics Committee of Shengjing Hospital (Ethic No. 2013PS33K).
RESULTS:
A duplication (ChrX:153302641_153503563) and four breakpoints were identified on the X chromosome of the fetus' father. Bioinformatic analysis revealed that the duplicated region has involved exons 1 to 3 and part of the 5'-UTR of the MECP2 gene, which was inserted into the Xp11 region. Additionally, an inversion was detected in the Xp11 region adjacent to the duplicated segment. RT-PCR results showed normal level of MECP2 mRNA expression. The Xq28 duplication has not encompassed the entire MECP2 gene, nor disrupted its structure or altered its expression.
CONCLUSION
WGS has enabled more precise diagnosis of chromosomal structural variants and provided guidance for accurate genetic counseling for the affected families.
Humans
;
Female
;
Chromosomes, Human, X/genetics*
;
DNA Copy Number Variations/genetics*
;
Whole Genome Sequencing/methods*
;
Methyl-CpG-Binding Protein 2/genetics*
;
Pregnancy
;
Male
;
Adult
6.Protective effect of stereotactic neuroendoscopic hematoma evacuation on neurological function in hypertensive intracerebral hemorrhage patients
Jie GAO ; Yu YUAN ; Mingyue LI ; Ming ZHANG ; Xu LIU
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(2):202-205
Objective To compare the effects of stereotactic endoscopic hematoma evacuation on elderly patients with hypertensive intracerebral hemorrhage.Methods A total of 220 patients with hypertensive intracerebral hemorrhage in the basal ganglion admitted to our hospital from January 2020 to December 2023 were retrospectively recruited.According to their surgical treat-ment,they were divided into an observation group(stereotactic endoscopic hematoma evacuation,n=100)and a control group(craniotomy hematoma removal surgery,n=120).Postoperative recovery was observed and compared between the two groups.Results There was no significant difference in operation time between the observation group and the control group(94.56±14.75 min vs 94.03±14.50 min,t=0.268,P=0.789).No statistical differences were observed in the NIHSS score before operation between the two groups(P=0.058),but the observation group obtained significantly lower NIHSS scores in 3 and 6 months after surgery(5.90±4.02 vs 9.23±3.47,P=0.000;4.54±2.56 vs 6.50±3.07,P=0.000).There were no significant differences in GOS score and incidence of postoperative complications between the two groups(P>0.05).Conclusion Stereotactic endoscopic hematoma evacuation can improve postoperative neurological function in patients with hypertensive intracerebral hemorrhage in the basal ganglia region.
7.Differences in mercury dissolution from HgS-containing traditional medicines under simulated gastrointestinal conditions
Ming ZHANG ; Yuan-can XIAO ; Jing ZHAO ; Hai-ying TONG ; Xiao-yu WANG ; Wen-bin ZHOU ; Hong-tao BI ; Li-xin WEI
Chinese Traditional Patent Medicine 2025;47(8):2607-2611
AIM To investigate the variations in mercury dissolution from HgS-containing traditional medicines in three kinds of simulated gastrointestinal dissolution media.METHODS 39 batches of 15 types of HgS-containing traditional medicines were collected,total mercury content and dissolved mercury concentrations in simulated gastric fluid,simulated intestinal fluid,and L-cysteine-containing simulated intestinal fluid were measured.The maximum daily intake of total mercury and soluble mercury was calculated based on the maximum daily clinical dosage.RESULTS Among the 15 types of medicines,the maximum daily intake of total mercury varied by 156 times,the daily intake of soluble mercury varied by 3 502 times in simulated gastric fluid,313 times in simulated intestinal fluid,and 10 663 times in L-cysteine-containing simulated intestinal fluid,approximately.CONCLUSION For the 15 types of HgS-containing traditional medicines,the daily maximum intake of soluble mercury showed greater variations than that of total mercury.Soluble mercury concentration is more closely correlated with intestinal absorption of mercury and thus represents a more rational quality control indicator for HgS-containing traditional medicines.
8.Mechanisms and intervention strategies of aging based on epigenetics
Li-yuan ZHANG ; Hao-nan SHI ; Wen-feng ZHANG ; Ming-qian ZHANG ; Zi-yang ZHAO ; Zhen-zhen CHENG ; Ti ZHANG ; Zhen-teng YAN ; Jian-ning SUN ; Shi-fen DONG
Chinese Pharmacological Bulletin 2025;41(12):2230-2235
Aging is comprehensively influenced by multiple fac-tors such as internal genes,cellular metabolism,external envi-ronment,and lifestyle habits.Among them,epigenetic regula-tion plays a core role.Epigenetic modifications,including DNA methylation,histone modification,heterochromatin remodeling,and non-coding RNA regulation,act in concert with the three-di-mensional genome architecture to precisely regulate gene expres-sion.This review elaborates on the factors influencing epigenetic regulation,as well as the mechanisms of how epigenetics affects the occurrence of organismal aging and the corresponding inter-vention strategies,providing relevant insights for uncovering the mechanisms of aging and preventing/treating aging-related disea-ses.
9.Feasibility study on road-rail medical vehicles
Jian-kang WANG ; Pei TIAN ; Fan WU ; Yun-ming LI ; Xia ZHANG ; Mu YUAN ; Xiao-li XU
Chinese Medical Equipment Journal 2025;46(10):84-90
The feasibility for the development of road-rail medical vehicles was discussed.The gap between China's ground medical evacuation system and medical evacuation requirements was analyzed,and the limitations of the existing mobile medical units in China were introduced.The key points for developing road-rail medical vehicles were discussed.The road-rail medical vehicle would be an ideal tool for casualty treatment and rapid evacuation at war time and peace time,which could be a future development direction of the road-rail vehicle and medical train.[Chinese Medical Equipment Journal,2025,46(10):84-90]
10.Analysis of the association between patent foramen ovale and migraine:advances in biomarker and imaging research
Kai-yuan LIU ; Ji-zhe XU ; Ming BAI ; Qiang WANG ; Li-he YAO
Chinese Journal of Interventional Cardiology 2025;33(9):516-522
Patent foramen ovale(PFO)demonstrates significant comorbidity with migraine,but its causal relationship and the efficacy of transcatheter closure remain controversial.This systematic review examines potential biomarkers and relevant imaging assessments for PFO-associated migraine,aiming to provide a theoretical foundation for clinical diagnosis and treatment.Key biomarkers include platelet activation markers,calcitonin gene-related peptide,homocysteine,and platelet-to-lymphocyte ratio.Imaging evaluations encompass right-to-left shunt grading(transthoracic echocardiography,transcranial Doppler ultrasound),cerebrovascular breath-holding index,characteristics of white matter hyperintensities,alterations in resting-state functional magnetic resonance imaging(rs-f-MRI)brain networks,in-situ thrombi detected by optical coherence tomography,and electroencephalogram(EEG)power spectral features.Research indicates that integrating biomarkers with imaging technologies enhances diagnostic discrimination and treatment outcome prediction.Current challenges include unclear causal relationships and insufficient standardization of detection methods.Future efforts require multidisciplinary collaboration to establish personalized diagnostic and therapeutic frameworks through multimodal indicators,thereby advancing precise prevention and treatment strategies for PFO-related migraine.

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