1.Neuroprotective effect of edaravone dexborneol on rats with intracerebral hemorrhage
Zhixuan WU ; Maojuan WANG ; Zuoxiao LI
Journal of Chongqing Medical University 2025;50(8):1029-1034
Objective:To investigate the role and possible mechanism of edaravone dexborneol in the prevention and control of patho-logical injury of brain tissue around hematoma after intracerebral hemorrhage(ICH).Methods:A total of 176 Sprague-Dawley rats were randomly divided into sham-operation group,ICH group,edaravone group,and edaravone dexborneol group,with 44 rats in each group.All rats except those in the sham-operation group were used to establish a rat model of acute ICH,and each group was further di-vided into 1-day,3-day,7-day,and 14-day subgroups according to the time of evaluation,with 11 rats in each subgroup.At 2 hours after modeling,drugs were administered via intraperitoneal injection,i.e.,6 ml/kg normal saline for the sham-operation group and the ICH group,6 mg/kg edaravone for the edaravone group,and 7.5 mg/kg edaravone dexborneol for the edaravone dexborneol group,fol-lowed by subsequent administration every 12 hours until day 14.The modified Neurological Severity Score(mNSS)was used to assess neurological function;the wet-dry weight method was used to measure the water content of brain tissue;the biochemical methods were used to measure nitric oxide(NO)and total antioxidant capacity(T-AOC)in brain tissue around the hematoma;immunohistochemistry was used to measure the content of CD16 and CD206 in brain tissue around the hematoma.Results:The mNSS score on day 3(peak of the disease)was 0.6±0.5 for the sham-operation group,14.0±1.6 for the ICH group,9.8±0.8 for the edaravone group,and 10.4±1.1 for the edaravone dexborneol group,with a water content of 63.2±2.14,85.61±1.43,81.48±1.9,and 76.77±1.44,respectively,and the content of NO was 2.45±0.46,9.98±0.54,8.77±0.36,and 7.92±0.43,respectively;the content of T-AOC was 0.67±0.02,0.74±0.03,0.78±0.02,and 0.84±0.03,respectively;the content of CD16 was 143.8±15.82,3 673.81±166.33,2 970.74±132.75,and 2 521.69±140.74,respectively;the content of CD206 was 548.46±93.68,726±97.81,915.28±100.33,and 1 119.51±160.52,respectively.There were significant differences in these indica-tors between the edaravone dexborneol group and the other three groups(all P<0.05).Conclusion:Edaravone dexborneol can alleviate neurological deficit caused by ICH and exert a neuroprotective effect by reducing brain tissue edema around the hematoma,alleviating oxidative stress,and regulating the polarization of microglial cells.
2.Protective Effect of MicroRNA-200a&c on Angiostrongylus cantonensis-induced Demylinating Optic Neuritis in Balb/c Mice
Zhixuan MA ; Zhen NIU ; Liang YANG ; Xiaojie WU ; Zhongdao WU ; Ying FENG
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(4):619-627
[Objective]To investigate the protective effect of overexpressed miRNA-200a&c on Angiostrongylus cantonensis-induced demyelinating optic neuritis in Balb/c mice.[Methods]SPF-grade Balb/c mice(2-3 weeks old)were divided into four groups:a normal group,and three A.cantonensis-infected groups at 7,14,and 21 days post-infection(dpi).Body weight,survival status,neurobehavioral scores,and visual function scores were recorded.Visual evoked potential(VEP)was used to detect visual damage,and transmission electron microscope(TEM)was applied to observe ocular structural changes.On day 7 post-infection,mice were stereotactically injected with exogenous miRNA-200a&c mimics into the lateral ventricle,and then divided into four groups:normal control,A.cantonensis-infected(AC-21 dpi),A.cantonensis-infected+negative control(AC+NC),and A.cantonensis-infected+overexpressed miRNA-200a&c(AC+miRNA-200a&c)mimics.VEP and TEM were repeated to assess visual damage and ocular structural changes.Immunofluorescence was performed to quantify retinal ganglion cells(RGCs)and oligodendrocytes(OLs)in the optic nerve.[Results]At 21 dpi,some mice exhibited complete eyelid closure(32.52±4.67)%or ocular atrophy(15.79±3.23)%,weight loss(P<0.05)and altered consciousness.Neurobehavioral scores significantly decreased(P<0.01),with a 68%decline in rotarod performance;some mice even displayed hemiplegia,slowed movement,ataxia,and directional deficits.Additionally,a subset of mice showed diminished sensory responses,unilateral vision loss(83%reduction in optokinetic threshold),and impaired visual function(P<0.05).VEP results revealed a mild prolongation of latency in infected mice at 21 dpi(P<0.05),predominantly affecting one eye.Following overexpression of miRNA-200a&c,compared with the 21 dpi group,VEP showed significantly shortened P1 latency(P<0.05);TEM showed alleviated cytoplasmic swelling of RGCs,and improved compactness and uniformity of myelin sheath(P<0.05);immunofluorescence showed increased numbers of RGCs and OLs with improved cell alignment(P<0.05).[Conclusions]A.cantonensis infection induces demyelinating optic neuritis in Balb/c mice.Overexpression of miRNA-200a&c alleviates the resulting damage and ameliorates ocular injury.
3.Untargeted Metabolomics Analysis of Demyelination in the Brain of Balb/c Mice Infected by Angiostrongylus cantonensis
Zhen NIU ; Xiaojie WU ; Liang YANG ; Zhixuan MA ; Junxiong YANG ; Ying FENG
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(2):293-300
[Objective]To investigate the demyelination induced by Angiostrongylus cantonensis(AC)infection in the brain of Balb/c mice and analyze the untargeted metabolomic changes in the corpus callosum,aiming to elucidate the underlying mechanisms.[Methods]Balb/c mice were randomly assigned to a control group(n=6)and an infection group(n=6).The infection group was orally administered 30 third-stage larvae of AC,while the control group received an equal volume of saline.Body weight,visual function,and behavioral scores were measured on post-infection 3,6,9,12,15,18,and 21 days to assess neurological alterations.After 21 days,brain tissues were harvested for immunofluorescence staining,hematoxylin-eosin(HE)staining,and transmission electron microscopy to examine morphological changes in brain myelin and retina.Metabolomics analysis was performed,and differential metabolites were identified using volcano plots and heatmaps.The distribution of fold changes and bar charts were used to profile the key metabolites.These differential metabolites were then subjected to Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis and regulatory network analysis.[Results]On the 9th day after AC infection,Balb/c mice showed a decline in neurological behavioral scores(P<0.05).By day 15,visual scores decreased(P<0.05),and by day 21,significant weight loss(P<0.001)and mortality were observed.Concurrently,transmission electron microscopy and immunofluorescence staining revealed significant myelin damage in the corpus callosum and a marked reduction in oligodendrocytes(P<0.001).HE staining showed severe retinal ganglion cell damage.Metabolomic analysis revealed that glycerophospholipids were the most abundant differential metabolites,with steroids and sphingolipids being relatively less abundant.Cholesteryl ester CE(20:2)was significantly upregulated(P<0.001),while phosphatidylmethanol(18:0_18:1)was significantly downregulated(P<0.01).KEGG enrichment and regulatory network analyses demonstrated that the differential metabolites were mainly enriched in metabolic pathways like steroid biosynthesis,bile secretion,and cholesterol metabolism,and were involved in key metabolic pathways such as sphingolipid metabolism,neural signal regulation,and glycerophospholipid metabolism.[Conclusions]AC infection affects the metabolic state of mice via multiple pathways,modifying the levels of metabolites crucial for myelination and myelin stability.Demyelination may be closely linked to the disruption of these key metabolic pathways,particularly the dysregulation of cholesterol and sphingolipid metabolism,potentially playing a central role in demyelination onset.Furthermore,alterations in phospholipid metabolism and abnormal nerve signaling regulation may exacerbate myelin damage.
4.Protective Effect of MicroRNA-200a&c on Angiostrongylus cantonensis-induced Demylinating Optic Neuritis in Balb/c Mice
Zhixuan MA ; Zhen NIU ; Liang YANG ; Xiaojie WU ; Zhongdao WU ; Ying FENG
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(4):619-627
[Objective]To investigate the protective effect of overexpressed miRNA-200a&c on Angiostrongylus cantonensis-induced demyelinating optic neuritis in Balb/c mice.[Methods]SPF-grade Balb/c mice(2-3 weeks old)were divided into four groups:a normal group,and three A.cantonensis-infected groups at 7,14,and 21 days post-infection(dpi).Body weight,survival status,neurobehavioral scores,and visual function scores were recorded.Visual evoked potential(VEP)was used to detect visual damage,and transmission electron microscope(TEM)was applied to observe ocular structural changes.On day 7 post-infection,mice were stereotactically injected with exogenous miRNA-200a&c mimics into the lateral ventricle,and then divided into four groups:normal control,A.cantonensis-infected(AC-21 dpi),A.cantonensis-infected+negative control(AC+NC),and A.cantonensis-infected+overexpressed miRNA-200a&c(AC+miRNA-200a&c)mimics.VEP and TEM were repeated to assess visual damage and ocular structural changes.Immunofluorescence was performed to quantify retinal ganglion cells(RGCs)and oligodendrocytes(OLs)in the optic nerve.[Results]At 21 dpi,some mice exhibited complete eyelid closure(32.52±4.67)%or ocular atrophy(15.79±3.23)%,weight loss(P<0.05)and altered consciousness.Neurobehavioral scores significantly decreased(P<0.01),with a 68%decline in rotarod performance;some mice even displayed hemiplegia,slowed movement,ataxia,and directional deficits.Additionally,a subset of mice showed diminished sensory responses,unilateral vision loss(83%reduction in optokinetic threshold),and impaired visual function(P<0.05).VEP results revealed a mild prolongation of latency in infected mice at 21 dpi(P<0.05),predominantly affecting one eye.Following overexpression of miRNA-200a&c,compared with the 21 dpi group,VEP showed significantly shortened P1 latency(P<0.05);TEM showed alleviated cytoplasmic swelling of RGCs,and improved compactness and uniformity of myelin sheath(P<0.05);immunofluorescence showed increased numbers of RGCs and OLs with improved cell alignment(P<0.05).[Conclusions]A.cantonensis infection induces demyelinating optic neuritis in Balb/c mice.Overexpression of miRNA-200a&c alleviates the resulting damage and ameliorates ocular injury.
5.Research on the Diagnostic Criteria for Dampness Syndrome Based on Consensus Method
Qian LI ; Wenzhen WU ; Zhixuan AI ; Lilei ZHOU ; Shujun LIU ; Xiaobo YANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(6):1660-1667
Objective To establish diagnostic criteria for dampness syndrome through scientific and normative research methods.Methods The basis for syndrome differentiation of dampness syndrome was comprehensively integrated through literature research and structured tools,and in-depth investigation was carried out on the connotation and extension of dampness syndrome,judgment basis and criteria construction through questionnaire surveys and consensus conference method.Results Thirty-six items for syndrome differentiation of dampness syndrome were obtained through literature research.Through the questionnaire surveys,some experts suggested that the diagnosis mode of dampness syndrome should be in line with the clinical practice requirements.Accordingly,we were deep in thought about the key issue of"how to establish accurate diagnostic criteria".After in-depth investigation,we found that the dampness syndrome had specific and sensitive indicators.And 11 specific and 19 sensitive indicators were determined.Furthermore,according to the experts'suggestions,the specific indicators were classified into three categories based on dampness characteristics.Meanwhile,we investigated the diagnosis attributes of Chinese medicine syndromes and summarized them into four corresponding modes.Based on this,specificity mode and similarity/consistency mode should be adopted for diagnostic criteria for dampness syndrome.In addition,the judgment form in accord with the diagnostic attributes of dampness syndrome was determined.Conclusion This diagnostic criteria can provide a basis for the clinical diagnosis of dampness syndrome.Besides,this study explored the diagnostic attributes of Chinese medicine syndromes,which could provide reference for the development of other Chinese medicine syndrome criteria.
6.Selection and Optimization Management of in Vitro Diagnostic Reagents for Clinical Examination in Beijing Hospital
Jingchen SONG ; Chuanbao LI ; Yuanyuan GAI ; Suowei WU ; Lei LIU ; Xuying LI ; Zhixuan GUO ; Deming YAO
Journal of Modern Laboratory Medicine 2024;39(3):194-198
Objective To form the in vitro diagnostic reagents(IVD)selection and optimization management plan and management database,and optimize the IVD management work.Methods Through the analysis of the policy background and the current management status of the IVD clinical laboratory in Beijing Hospital,the selection and optimization management plan for existing and newly applied laboratory IVD was formulated based on clinical needs.The IVD of the whole hospital was selected and optimized by combing projects,open bidding,innovative quotation methods,on-site review and other steps.The IVD management database and qualification database of Beijing Hospital was formed,and the effect from the aspects of compliance,work efficiency and cost control was evaluated.Results The selection and optimization of 1 737 IVDs in the whole hospital were completed according to the formulated IVD selection and optimization management plan.The implementation of management plan improved the work efficiency.The content of review in an average meeting was increased by more than 10 times,and the frequency of new applications for IVD access was accelerated,while the IVD cost was reduced,and the average purchase amount of the whole hospital was reduced by about 15%.The prices of key IVD products were lower after selection than before selection,and the difference was significant(t=2.493,P=0.034).Conclusion The management scheme of IVD selection and optimization was feasible,and it could achieve the goal of ensuring compliance,improving efficiency and reducing costs.
7.Design and Effect Evaluation of in Vitro Diagnostic Reagents for Beijing Hospital Based on Performance Management of the Whole Process Closed-loop Management
Jingchen SONG ; Zhixuan GUO ; Jingjing DOU ; Lei LIU ; Suowei WU ; Chuanbao LI
Journal of Modern Laboratory Medicine 2024;39(4):197-202
Objective To establish in vitro diagnostic(IVD)reagents closed-loop management scheme for the whole process and implement,and optimize the IVD management.Methods Based on the status quo of IVD management in Beijing Hospital,the closed-loop management scheme of the whole IVD process was designed,such as IVD application,IVD selection,IVD subscription,IVD purchase,IVD receipt,IVD inbound and outbound,and IVD use.Key indicators were selected to establish an evaluation framework.Management data,procurement data and testing data before(2020)and after(2023)implementation of the program were collected and counted by means of interviews and consulting relevant information systems,and then process management,quality management and cost management were evaluated.Results The management process was optimized,the IVD purchase time was shortened by about 60%on average,the IVD purchase did not need manual processing,the order was split in real time and sent to the corresponding supplier,and the IVD collection time was shortened by about 75%on average.IVD and test quality management were satisfactory,supplier qualification perfection reached 100%,full marks were obtained in the inter-room quality assessment,and no IVD-related adverse events were observed.The cost management was effective,and the IVD procurement cost was reduced by about 15%.IVD cost fine management models were established for four items,namely,human immunodeficiency virus antibody assay,hepatitis C antibody assay,treponemal antibody assay and hepatitis B surface antigen quantitative assay.The average value of IVD loss was 0.07%~1.21%,and the standard deviation was 0.07%~0.66%.Conclusion The IVD whole process closed-loop management scheme is feasible,which can improve the efficiency of IVD management,ensure the quality of IVD and detection,reduce the cost of IVD,and refine the cost management work.
8.Innovative cultural construction for empowerment of high-quality development in public hospitals
Kai FENG ; Jie WU ; Zhixuan LI
Modern Hospital 2024;24(5):684-687
Hospital culture constitutes the core competitiveness of modern hospitals and serves as the intrinsic driving force for the development of public hospitals.It permeates and affects various aspects of hospital operations,including medical quality,modern management,scientific research and teaching,and talent cultivation.An advanced hospital culture is instrumen-tal in bolstering a hospital's core competitiveness,establishing a positive image,fostering harmonious doctor-patient relation-ships,and facilitating high-quality development.The First People's Hospital of Changzhou,under the guidance of Party-building theories,has adopted the"532"development strategy.The hospital has pursued a"Five Implementations"approach to cultivate its spirit,system,service,integrity,and brand.This strategy is pivotal in solidifying the ideological foundation among staff through the development of a robust spiritual culture.It has also enhanced the level of scientific management by strengthening in-stitutional culture,improved patient experience through the refinement of service culture,raised awareness in medical service by constructing a culture of integrity,and expanded industry influence by shaping a distinct brand culture.These efforts have contin-uously elevated the hospital's management standards and,patient experience,thus promoting its high-quality development.
9.Effect of squatting toilet behavior on gastric transit time and complete examination rate of small bowel during capsule endoscopy
Xia LI ; Song HE ; Xiaomei WANG ; Zhixuan WU
Journal of Army Medical University 2024;46(11):1265-1269
Objective To study the effect of squatting toilet behavior on gastric transport time(GTT)and complete examination rate of small bowel(CER)during capsule endoscopy.Methods A total of 122 patients who underwent capsule endoscopy at the Second Affiliated Hospital of Chongqing Medical University from January to December 2019 were recruited and randomly divided into test group(n=63)and control group(n=59).The patients of the test group were asked to take squatting posture for toileting after swallowing the capsule,while those of the control group were asked to take sitting in defecation if needed.GTT,small bowel transit time(SBTT),CER and diagnostic yield(DY)were compared between the 2 groups.Results There were no significant differences in gender,age and conditions during hospitalization between the test group and the control group.The test group obtained obviously higher CER(92.06%vs 79.66%,P=0.048)and shorter GTT(26.7 vs 45.6 min,P=0.027)when compared with the control group.No statistical differences were seen in SBTT and DY between the 2 groups.Conclusion Squatting posture for toileting of patients accepted capsule endoscopy can reduce the transit time of capsules in the stomach and increase the CER.
10.CBX7 Rejuvenates Late Passage Dental Pulp Stem Cells by Maintaining Stemness and Pro-angiogenic Ability
Yu WU ; Bing LI ; Dandan YU ; Zhixuan ZHOU ; Ming SHEN ; Fei JIANG
Tissue Engineering and Regenerative Medicine 2023;20(3):473-488
BACKGROUND:
Ever-growing tissue regeneration causes pressing need for large population of stem cells. However, extensive cell expansion eventually leads to impaired regenerative potentials. In this study, chromobox protein homolog 7 (CBX7) was overexpressed to rejuvenate late passage dental pulp stem cells (DPSCs-P9).
METHODS:
The recruitment of copper ions (Cu2+ )-activated hypoxia-inducible factor-1a (HIF-1a) to the CBX7 gene promoter was confirmed by chromatin immunoprecipitation assay. Functions subsequent to Cu2+ -induced or recombinant overexpression of CBX7 on proliferation, multipotency, odontoblastic differentiation and angiogenesis were investigated in vitro, while murine subcutaneous transplantation model was used to further detect the effects of Cu2+ -induced CBX7 overexpression in vivo.
RESULTS:
Our data displayed that CBX7 overexpression maintain proliferation and multipotency of DPSCs-P9 almost as strong as those of DPSCs-P3. Both gene level of odontoblast-lineage markers and calcium precipitation were nearly the same between CBX7 overexpressed DPSCs-P9 and normal DPSCs-P3. Moreover, we also found upregulated expression of vascular endothelial growth factor in DPSCs-P9 with CBX7 overexpression, which increased the number of capillary-like structures and migrating co-cultured human umbilical vein endothelial cells as well. These findings indicate CBX7 as an effective factor to rejuvenate late passage stem cells insusceptible to cell expansion. Cu2+ has been proved to achieve CBX7 overexpression in DPSCs through the initiation of HIF-1a-CBX7 cascade. Under Cu2+ stimulation since P3, DPSCs-P9 exhibited ameliorated regenerative potential both in vitro and in vivo.
CONCLUSION
Long-term stimulation of Cu2+ to overexpress CBX7 could be a new strategy to manufacture large population of self-renewing stem cells.

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