1.Modified Shuyu Pills regulate VTA-NAc circuit myelination to ameliorate depressive behaviors in mouse model of vascular dementia via LDLR/MEK/ERK signaling pathway.
Song JING ; Zi-Hu TAN ; Qiong YANG
China Journal of Chinese Materia Medica 2025;50(16):4555-4563
This study aims to explore the effects and potential mechanisms of Modified Shuyu Pills in ameliorating depressive behaviors in the mouse model of vascular dementia(VaD). Seventy-two three-month-old male C57BL/6 mice were assigned into six groups: sham, model, low-, medium-, and high-dose Modified Shuyu Pills, and fluoxetine. The other five groups except the sham group underwent bilateral common carotid artery stenosis combined with chronic unpredictable stress. Depressive behaviors were assessed by the sucrose preference test and tail suspension test. Cerebral blood flow was measured by laser speckle imaging. Protein levels of low density lipoprotein receptor(LDLR), mitogen-activated protein kinase kinase(MEK), phosphorylated(p)-MEK, extracellular signal-regulated kinase(ERK), and p-ERK in the ventral tegmental area(VTA) and nucleus accumbens(NAc) were determined by Western blot. The fluorescence intensity of myelin basic protein(MBP) in the VTA and NAc were measured by immunofluorescence. Myelin sheath morphology in the VTA and NAc was observed by luxol fast blue staining, and the ultrastructure of myelin sheath in the VTA and NAc was examined by transmission electron microscopy. In the tail suspension test, the immobility time of the model group was longer than that of the sham group(P<0.01). In the sucrose preference test, the sucrose preference rate of the model group was lower than that of the sham group(P<0.01). After intervention with Modified Shuyu Pills, the immobility time in the tail suspension test was shortened(P<0.01), and the sucrose preference rate increased(P<0.01). Laser speckle imaging results showed that compared with the sham group, the model group showed reduced cerebral blood flow(P<0.01), and the reduction was reversed by medium-and high-dose Modified Shuyu Pills(P<0.01). Western blot results indicated that the relative expression levels of LDLR, p-MEK/MEK, and p-ERK/ERK in the VTA and NAc of the model group were lower than those in the sham group(P<0.01). Medium-and high-dose Modified Shuyu Pills reversed this trend(P<0.01). Immunofluorescence results showed that the fluorescence intensity of MBP in the VTA and NAc of the model group was lower than that of the sham group(P<0.01). The medium-and high-dose Modified Shuyu Pills groups showed increased fluorescence intensity of MBP in the VTA compared with the model group(P<0.01). In the NAc, the fluorescence intensity of MBP in all the groups of Modified Shuyu Pills increased to varying degrees compared with that in the model group(P<0.01). Luxol fast blue staining results showed that the model group presented lighter staining intensity and looser arrangement of myelin fibers than the sham group, indicating significant demyelination in the model group. However, after intervention with medium-and high-dose Modified Shuyu Pills, the staining intensity and myelin sheath structure in the VTA and NAc were improved. Transmission electron microscopy results revealed that the myelin sheath in the VTA and NAc of the sham group was intact and dense, while the model group exhibited extensive myelin loss, with myelin sheath degeneration and disintegration. After intervention with Modified Shuyu Pills, the myelin sheath loss in the VTA and NAc of mice was reduced, and the proportion of myelinated tissue increased. In summary, Modified Shuyu Pills may promote myelination via the VTA-NAc circuit by upregulating the LDLR/MEK/ERK signaling pathway, thereby ameliorating depressive-like behaviors in VaD mice.
Animals
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Male
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Drugs, Chinese Herbal/administration & dosage*
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Mice
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Ventral Tegmental Area/metabolism*
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Mice, Inbred C57BL
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Disease Models, Animal
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Depression/genetics*
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Receptors, LDL/genetics*
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Dementia, Vascular/psychology*
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MAP Kinase Signaling System/drug effects*
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Nucleus Accumbens/metabolism*
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Behavior, Animal/drug effects*
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Humans
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Myelin Sheath/drug effects*
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Extracellular Signal-Regulated MAP Kinases/genetics*
2.Research progress on paranasal sinuses morphology
Hai-Jun LI ; Ya GAO ; Qiong SONG
Acta Anatomica Sinica 2025;56(4):499-505
Paranasal sinuses,also known as nasal sinuses,are a collective term for the air-filled cavities surrounding the nasal cavity within the skull.The paranasal sinuses comprise the maxillary sinuses,ethmoid sinuses,frontal sinuses,and sphenoid sinuses,which are bilaterally symmetrical,totaling four pairs.Due to the deep-seated anatomical location of the paranasal sinuses within the skull,accurate measurement has been historically challenging,resultsing in relatively limited early investigations in this field.In recent years,with the continuous advancement of imaging technologies,research on the morphology of the paranasal sinuses has progressively increased.In this paper we provides a systematic review of domestic and international research on the variations of paranasal sinuses among different populations,factors influencing their growth and development,evolutionary characteristics,and measurement method-ologies.Furthermore,a concise retrospective analysis and future prospects for studies on the paranasal sinuses within the domestic context are provided.
3.Evaluation and Analysis of the Effectiveness of the Reform of Teaching Mode in Health Statistics by Postgraduate Students
Liping HE ; Xiaoxiao SONG ; Wei CHANG ; Qiong MENG ; Zhen YU ; Jieyu HE ; Hongrui ZHAO ; Jiabi QIN
Journal of Kunming Medical University 2025;46(8):136-146
Objective To investigate the effectiveness of the curriculum design and teaching mode reform in Health Statistics through the assessment by postgraduate students so as to enhance the teaching performance of the course.Methods A questionnaire survey was conducted among the postgraduate students of grade 2023 at a certain medical university.The survey covered such aspects as students'mastery and application of the course learning content,their evaluation and satisfaction with the course,etc.Descriptive approaches were employed to analyze and summarize the data.Results Students achieved a good command of theoretical knowledge and its application.They highly evaluated the teacher,the course content and its practicality,demonstrated a strong interest in learning,expressed a high level of satisfaction with the course,and manifested a strong willingness to continue studying the course.The learning of the course met the expectations of the students.The final exam scores in the later stage of curriculum reform(78.60±10.58)was higher than that before the reform(75.78±7.97,P<0.05);the excellent rate after the reform was 53.6%,which was higher than the 33.5%before the reform(P<0.05).Conclusion The construction of a course system that integrates knowledge,skills the mixed teaching mode of case-based teaching and the combination of theory and statistical software package operation are beneficial for enhancing postgraduate students'learning and application of the course in health statistics.It also strengthens the design and training of course application aspects for students in clinical medicine and dental medicine disciplines.
4.Progress in Methods for Electrochemical Detection of Thrombin
Di WU ; Xi-Yao ZHANG ; Jing-Jing XU ; Yi-Ting CHEN ; Wen-Qi TANG ; Wen-Hui XU ; Song-Min CHEN ; Qiong HU ; Li NIU
Chinese Journal of Analytical Chemistry 2025;53(9):1403-1410
As a serine protease,thrombin can convert soluble fibrinogen into insoluble fibrin and plays a pivotal role in the coagulation cascade.Therefore,the accurate quantitative assay of thrombin levels is of great value in the evaluation of coagulation function,clinical screening and prognostic monitoring of coagulation-related diseases,and screening of drugs for targeted therapy.Existing methods for thrombin detection can be divided into two categories,e.g.,the assay of concentration levels using nucleic acid aptamers as the affinity elements and the assay of activity levels based on the hydrolytic cleavage of substrate peptides.In recent years,electrochemical biosensors have attracted much attention in thrombin detection due to high sensitivity,high selectivity,simple instrument,fast response,and good portability.In this review,the latest research progress in methods for electrochemical detection of thrombin was summarized,focusing on the detection principles and the applied signal amplification strategies of related electrochemical biosensors.In addition,the challenges with respect to the practical use of electrochemical thrombin biosensors and the prospects were discussed.
5.Influencing factors for atrial fibrillation in elderly patients with heart failure and construction of a nomogram model
Yakun SU ; Tingting LIN ; Qiong WANG ; Fengde LI ; Junying SONG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(8):1010-1015
Objective To elucidate the independent risk factors for AF in elderly patients with HF,develop a nomogram prediction model,and assess its predictive value for AF in elderly HF pa-tients.Methods A retrospective study was conducted on 299 patients of first HF hospitalization in Hengshui People's Hospital from June 2019 to December 2023,and based on the presence or absence of AF,they were divided into an AF group(133 cases)and a non-AF group(166 cases).The patients admitted from June 2019 to December 2022 were assigned into a modeling cohort(206 cases),while those from January 2023 to December 2023 into a validation cohort(93 cases).The general data were collected.Multivariate logistic regression analysis was performed on the modeling cohort to identify the independent predictors of AF in elderly HF patients,and a nomo-gram prediction model was constructed.ROC curve,calibration curve and clinical decision curve analyses were applied to evaluate the discrimination,calibration and clinical practicability of the prediction model.Results Multivariate logistic regression analysis revealed that the etiology of HF(CHD vs HP,OR=0.610,95%CI:0.301-1.250,P=0.178;CMD vs HP,OR=0.213,95%CI:0.052-0.883,P=0.033),LAD(OR=1.081,95%CI:1.020-1.152,P=0.015),HF classifi-cation(HFmrEF vs HFrEF,OR=5.897,95%CI:2.448-14.201,P=0.000;HFpEF vs HFrEF,OR=7.211,95%CI:2.522-20.640,P=0.001),pre-albumin(PALB)(OR=0.438,95%CI:0.217-0.901,P=0.030),UAC(OR=2.186,95%CI:1.075-4.430,P=0.025),and direct biliru-bin(DBi)(OR=4.531,95%CI:2.052-9.990,P=0.000)were independent risk factors for AF in the elderly HF patients.ROC curve analysis showed the AUC value of the prediction model based on these factors in the modeling cohort was 0.831,and the AUC value in the validation cohort was 0.840.Decision curve analysis indicated that the model possessed clinical practicability within a probability threshold range of 10%-82%for the modeling cohort and 12%-100%for the vali-dation cohort.Conclusion Our nomogram prediction model based on multivariate logistic regres-sion analysis exhibits good predictive value for the occurrence of AF in elderly HF patients,and can facilitate clinical decision-making on diagnosis and treatment.
6.Screening and validation of chemoresistance marker in lung adenocarcinoma based on gene expression profile
Handong Wei ; Shuxing Chen ; Linting Liu ; Zihan Jing ; Yiting Yang ; Qiong Song ; Wenchu Wang ; Chunlin Zou ; Lihui Wang
Acta Universitatis Medicinalis Anhui 2025;60(10):1818-1827
Objective:
To discover molecular markers associated with lung adenocarcinoma diagnosis/prognosis and drug resistance through screening of differentially expressed genes based on published chip data in gene expression databases using bioinformatics methods.
Methods:
Comprehensive analysis was performed in available mRNA microarray datasets including lung adenocarcinoma tissues dataset GSE32863 and lung adenocarcinoma taxane-platin resistance dataset GSE77209 from the gene expression omnibus(GEO) database. Gene ontology enrichment analysis, gene pathway enrichment analysis and protein interaction network analysis were performed based on significantly correlated genes. The expression level of genes was validated in the cancer genome atlas(TCGA) dataset. Survival differences were assessed by the log-rank test in TCGA lung adenocarcinoma dataset. Based on the publications genomics of drug sensitivity in cancer(GDSC) database in CellMiner cross database(CellMiner CDB), Pearson correlation analysis was used to analyze the correlation between differentially expressed genes and the half-maximal inhibitory concentration(IC50) of anticancer drugs.
Results :
There were a total of 77 genes which had a different expression in resistance lung adenocarcinoma cells and lung adenocarcinoma cancer tissues. The functional enrichment analysis showed that these co-different expression genes were mainly enriched in microtubule, extracellular exosome, cell cycle and signaling by nuclear receptors. Protein-protein interactions(PPI) network screened 6 most connected genes as molecular complex(MCODE). Among the MCODE, overexpressed ubiquitin conjugating enzyme E2 T(UBE2T), kinesin family member 20A(KIF20A), PCNA clamp associated factor(KIAA0101), pituitary tumor-transforming gene 1(PTTG1) and NIMA related kinase 2(NEK2) were associated with poor outcomes. Survival analysis results showed that these five genes were upregulated in lung adenocarcinoma tissues and drug-resistant cells and were significantly associated with poor prognosis in lung adenocarcinoma patients. Drug sensitivity analysis results suggested that high expression of PTTG1 and UBE2T was significantly associated with sensitivity to multiple anticancer drugs, including paclitaxel and docetaxel. RT-PCR validation showed that PTTG1 andUBE2T were highly expressed in docetaxel-resistant cells A549-TXR and H358-TXR.
Conclusion
PTTG1 andUBE2T holds the potential to be chemoresistance markers in lung adenocarcinoma.
7.Efficacy and immunological mechanisms of pegylated interferon α-2b in treatment-naive patients with chronic hepatitis B
Shufen SONG ; Fengxian JIN ; Yu LAN ; Gongchang ZHANG ; Zhiguo WU ; Yao ZHOU ; Qiong XIE ; Long YANG ; Shuilin SUN
Chinese Journal of Infectious Diseases 2025;43(1):14-23
Objective:To evaluate the efficacy and immunological mechanisms of pegylated interferon α-2b (Peg-IFNα-2b) antiviral therapy in treatment-naive patients with chronic hepatitis B(CHB).Methods:A total of 166 treatment-naive CHB patients, who were treated at Department of Infectious Diseases, the Second Affiliated Hospital of Nanchang University from March 2021 to March 2023, were enrolled in this study. All the patients received Peg-IFNα-2b therapy for 48 weeks. Serum hepatitis B virus (HBV) DNA, HBV serological markers, biochemical parameters, peripheral blood lymphocyte subsets and serum cytokine levels were detected and compared before and after treatment. Chi-square test, Mann-Whitney U test and paired sample t test were used for statistical comparison. Multivariate logistic regression analysis was used to analyze the influencing factors of hepatitis B surface antigen (HBsAg) seroconversion by stepwise regression method, and the receiver operator characteristic curve (ROC curve) was used to evaluate the predictive efficacy of immune indicators on HBsAg seroconversion. Results:Among the 166 treatment-naive CHB patients, the rate of HBV DNA negativity following 48 weeks of Peg-IFNα-2b therapy was 71.08%(118/166), the rate of hepatitis B e antigen (HBeAg) negativity was 32.05%(25/78), and the rate of HBsAg negativity was 20.48%(34/166). HBsAg negativity rate was 52.17%(24/46) in patients with baseline HBsAg<200 IU/mL, 10.26%(4/39) in patients with baseline HBsAg 200 to <1 200 IU/mL, and 7.41%(6/81) in patients with baseline HBsAg≥1 200 IU/mL, and the difference was statistically significant( χ2=39.37, P<0.001). After 48 weeks of treatment, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBil), and alpha-fetoprotein (AFP) were significantly lower than those before treatment ( Z=9.33, 8.58, 5.99, 2.36, respectively, all P<0.05). lmmune indicators were detected in 58 patients, and the proportion of peripheral blood lymphocytes increased significantly post-treatment, with notable increases in CD3 + CD8 + T/CD3 + T, CD3 + CD4 + DR + /CD3 + CD4 + , CD3 + CD8 + DR + /CD3 + CD8 + , CD3 + CD8 + CD38 + /CD3 + CD8 + , CD3 + CD8 + CD28 + /CD3 + CD8 + , and CD19 + B cells, and the differences were all statistically significant ( t=-2.56, t=-8.65, Z=-3.58, t=-3.66, Z=-3.04, t=-3.62, t=-3.87, respectively, all P<0.05). Conversely, the proportion of CD3 + , CD3 + CD4 + T/CD3 + T, CD3 + CD4 + CD45RO + /CD3 + CD4 + , CD3 + CD8 + CD45RO + /CD3 + CD8 + and the CD4 + /CD8 + ratio decreased significantly post-treatment ( t=3.13, t=5.61, t=3.69, Z=3.95, Z=7.33, respectively, all P<0.05). No significant differences were observed in the proportion of CD16 + CD56 + natural killer (NK) cells, CD3 + CD4 + CD28 + /CD3 + CD4 + , CD3 + CD4 + CD38 + /CD3 + CD4 + cells before and after treatment (all P>0.05). Serum levels of interleukin(IL)-8, IL-12P70, and IL-17 significantly decreased post-treatment ( Z=2.85, 3.26, 4.12, respectively, all P<0.05), while IL-2, IL-1β, and interferon(IFN)-α levels were significantly elevated compared to baseline ( Z=-4.92, -4.85, -9.01, respectively, all P<0.001). There were no significant differences in IL-4, IL-6, and IL-10 levels before and after treatment (all P>0.05). Logistic regression analysis identified CD3 + CD8 + T/CD3 + T(odd ratios ( OR)=1.198, 95%confidence interval( CI) 1.003 to 1.432, P=0.046), CD3 + CD4 + DR + /CD3 + CD4 + ( OR=1.185, 95% CI 1.035 to 1.357, P=0.014), CD3 + CD8 + DR + /CD3 + CD8 + ( OR=0.813, 95% CI 0.690 to 0.958, P=0.013), CD3 + CD4 + CD38 + /CD3 + CD4 + ( OR=0.678, 95% CI 0.488 to 0.940, P=0.020), CD3 + CD8 + CD38 + /CD3 + CD8 + ( OR=1.272, 95% CI 1.069 to 1.512, P=0.007), CD19 + B cells( OR=0.752, 95% CI 0.582 to 0.971, P=0.029), IL-2( OR=8.568, 95% CI 1.927 to 38.087, P=0.005), and IL-17( OR=0.728, 95% CI 0.535 to 0.989, P=0.042) as independent factors influencing HBsAg seroconversion. The area under the curve (AUC) of the proportion of dCD19 + B cells (the reciprocal of CD19 + B cells) for predicting HBsAg seroconversion was 0.716, the sensitivity was 0.636, and the specificity was 0.809. The AUC of IL-2 was 0.657, the sensitivity was 0.818, and the specificity was 0.404. The AUC of dIL-17 (the reciprocal of IL-17 levels) was 0.624, the sensitivity was 0.727, and the specificity was 0.489. The AUC of IL-2 and dIL-17 as a combined predictor was 0.830, the sensitivity was 0.909, and the specificity was 0.787. Conclusions:Peg-IFNα-2b demonstrates significant antiviral, biochemical, and serological responses in treatment-naive CHB patients, with enhanced efficacy in patients exhibiting HBsAg levels <200 IU/mL. In patients with HBsAg<200 IU/mL, the rate of HBsAg negativity reached 52.17%.Peg-IFNα-2b can regulate the immune function of patients with CHB by increasing the proportion of activated T lymphocyte subsets and functional subsets. The proportion of CD19 + B cells, IL-2 levels, and IL-17 levels hold predictive value for achieving HBsAg seroconversion.
8.Effects of tanshinone ⅡA on TNBS-induced mouse model of chronic colitis through PXR/NF-κB signaling pathway
Shan-shan CHEN ; Bing-bing SONG ; Xian-qiong GONG ; Jie ZHAO ; Kai-qing ZHANG ; Qiong WANG
Chinese Traditional Patent Medicine 2025;47(4):1129-1136
AIM To investigate the therapeutic mechanism of tanshinone ⅡA in a mouse model of chronic colitis induced by trinitrobenzene sulfonic acid(TNBS).METHODS The BALB/c mice were randomly divided into the control group,the model group,and the low-dose and high-dose tanshinone ⅡA groups(10,20 mg/kg).Chronic inflammatory bowel disease(IBD)was induced in the model and tanshinone ⅡA groups by epicutaneous application of 3.75 mg TNBS(dissolved in 48%ethanol),followed by intrarectal administration of TNBS(0.75,1.5 and 2.25 mg in 40%ethanol)on days 7,14 and 21.Starting on day 7 post-modeling,the mice underwent their 14-day consecutive dosing of corresponding drugs by gavage.The mice had their disease activity index(DAI)assessed;their colon length and weight measured;and their levels of inflammatory factors IFN-γ and TNF-α in the colon mucosa detected by ELISA.The wild-type and PXR-/-mice were randomly divided into the control group,the model group,and the tanshinone ⅡA group(20 mg/kg).After modeling and drug administration using the aforementioned method,Masson staining was used to assess the intestinal fibrosis;immunohistochemistry was employed to detect the colon expression of ZO-1 and Occludin proteins;and immunofluorescence was used to detect the colon expression of NF-κB p65.RESULTS Tanshinone ⅡA(20 mg/kg)reduced DAI scores,colon weight/length ratio,and the colon levels of IFN-γ and TNF-α of the mouse models(P<0.05,P<0.01).Compared with the WT control group,the WT model group and PXR-/-control group exhibited increased colon histopathological scores and fibrosis areas(P<0.01),decreased protein expressions of ZO-1 and Occludin(P<0.01),and increased expression of p-NF-κB p65(P<0.01).Compared with the WT model group,the WT tanshinone ⅡA group showed reduced colon weight/length ratio,histopathological scores,and fibrosis areas(P<0.01);increased protein expressions of ZO-1 and Occludin(P<0.05,P<0.01);and decreased expression of p-NF-κB p65(P<0.01).However,tanshinone ⅡA showed no significant therapeutic effect upon PXR-/-model mice(P>0.05).CONCLUSION Tanshinone ⅡA(20 mg/kg)can effectively alleviate TNBS-induced chronic colitis in mice,and this protective effect may be exerted by the modulation of PXR/NF-κB signaling pathway.
9.Effect of anticoagulation-free veno-venous extracorporeal membrane oxygenation in patients with severe chest trauma
Jie JIN ; Tingting AN ; Chengjian LI ; Qiong WU ; Yifan MA ; Huihui DING ; Tao SONG ; Lanjuan XU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2025;32(1):73-77
Objective To explore the feasibility and safety of non-anticoagulation veno-venous extracorporeal membrane oxygenation(VV-ECMO)in patients with severe chest trauma.Methods A retrospective cohort study method was used.A total of 19 patients with severe chest trauma who received VV-ECMO with a delayed anticoagulation strategy at Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2018 to October 2021 were included in the delayed anticoagulation group,and 20 patients with severe chest trauma who received VV-ECMO with a non-anticoagulation strategy from November 2021 to October 2024 were included in the non-anticoagulation group.The overall clinical characteristics of the patients were statistically analyzed,including gender,age,injury severity score(ISS),acute physiology and chronic health evaluationⅡ(APACHEⅡ),reason for VV-ECMO,use of vasoactive drugs,oxygenation index(PaO2/FiO2),and interval from injury to VV-ECMO.The primary outcomes were hemorrhagic and thrombotic complications.The secondary outcomes were blood transfusion during VV-ECMO,VV-ECMO time,mechanical ventilation time,intensive care unit(ICU)length of stay,and 28-day mortality.Results There was no significant difference in gender,age,ISS score,APACHEⅡscore,reason for VV-ECMO,use of vasoactive drugs,PaO2/FiO2,and interval from injury to VV-ECMO between the non-anticoagulation group and the delayed anticoagulation group.There was no significant difference in overall incidence of hemorrhagic and thrombotic between the two groups[incidence of hemorrhagic complications:15.0%(3/20)vs.31.6%(6/19),incidence of thrombotic:15.0%(3/20)vs.5.3%(1/19),both P>0.05].The infusion rate of 4 or more paked red blood cell(PRBC)within 24 hours during VV-ECMO in the non-anticoagulation group was significantly lower than that in the delayed anticoagulation group[5.0%(1/20)vs.31.6%(6/19),P<0.05].The amount of PRBC and platelet transfusion and the time on VV-ECMO in the non-anticoagulation group during VV-ECMO were significantly lower than those in the delayed anticoagulation group[PRBC(U):5.8±3.8 vs.8.1±3.1,platelets(U):1(0,1)vs.2(1,3),time on VV-ECMO(hours):71.55±24.37 vs.114.21±34.08,all P<0.05].There were no statistically significant differences in the amount of plasma and cryoprecipitate transfusion during VV-ECMO,mechanical ventilation time,ICU hospitalization time,and 28-day mortality between the two groups.Conclusion For patients with severe chest trauma receiving VV-ECMO withholding routine systemic anticoagulation did not result in thrombotic complications or higher mortality and required less PRBC and platelet transfusions.Non-anticoagulant VV-ECMO is safe and feasible for patients with severe chest trauma with high risk of bleeding.
10.Role of SIRT1 activation in neuronal ferroptosis in rats after traumatic brain injury: a randomized controlled trial
Jie JIN ; Tingting AN ; Qiong WU ; Xiangyang LI ; Yifan MA ; Huihui DING ; Tao SONG ; Chengjian LI ; Lanjuan XU
Chinese Journal of Neuromedicine 2025;24(8):780-789
Objective:To preliminarily explore whether sirtuin1 (SIRT1) activation can inhibit neuronal ferroptosis in rats after traumatic brain injury (TBI) by regulating hypoxia-inducible factor-1α (HIF-1α)-mediated glycolysis.Methods:(1) Six SD rats were randomly divided into sham-operated group and TBI group, with 3 rats in each group; TBI model in the TBI group was established by hydraulic impact method, and rats in the sham-operated group underwent same surgery without impact. Cortical tissues of the two groups were sent for tandem mass tag (TMT) labeled quantitative proteomics detection to analyze the differential expression proteome; Kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) were used to detect pathway enrichment of the screened differential proteins. (2) Twelve SD rats were randomly divided into sham-operated group and 1-day, 3-day and 7-day post-TBI groups, with 3 rats in each group. Treatment methods were the same as above; Western blotting was used to detect SIRT1 protein expression. (3) Forty-eight rats were randomly divided into sham-operated group, TBI group, TBI+vehicle group and TBI+SIRT1 agonist group, with 12 rats in each group; rats in the sham-operated group and TBI group accepted treatment as above; rats in the TBI+SIRT1 agonist group were intraperitoneally injected with SRT1720 (dissolved in ≤ 5% dimethyl sulfoxide, at a dose of 20 mg/kg) within 30 minutes after modeling, twice a day (with an interval of 12 hours); and rats in the TBI+vehicle group were injected with same dose of dimethyl sulfoxide at the same time. One d after modeling, neurological deficit was assessed using modified Neurological severity score (mNSS), brain water content was measured by dry-wet weight method, histopathological changes in the cortical lesions were observed by HE staining, mitochondrial ultrastructure was examined by transmission electron microscopy, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the brain tissues were detected by colorimetry, and protein expressions of SIRT1, HIF-1α (key protein in the glycolytic pathway), glutathione peroxidase 4 (GPX4, key protein in the ferroptosis pathway), and acyl-CoA synthetase long-chain family member 4 (ACSL4, key protein in the ferroptosis pathway) were evaluated by Western blotting.Results:(1) KEGG analysis revealed that the glycolysis pathway and HIF-1 signaling pathway were obviously enriched in the cortical tissues of rats in the TBI group compared with the sham-operated group; GSEA showed that the HIF-1 signaling pathway (mmu04066) and ferroptosis pathway (mmu04216) gene sets in the cortical tissues of rats in the TBI group exhibited enrichment trends compared with those in the sham-operated group. (2) Compared with the sham-operated group, the 1-day, 3-day, and 7-day post-TBI groups had significantly decreased SIRT1 protein expression ( P<0.05), with the most prominent decline in 1-day post-TBI group. (3) Compared with the TBI+vehicle group, rats in the TBI+SIRT1 agonist group showed significantly reduced mNSS score and brain tissue water content (9.83±1.17 vs. 7.66±1.21; [83.62±0.91]% vs. [80.09±0.68]%, P<0.05). HE staining indicated clearer structure of the cortical area at the injury sites, and improved neuron morphology in the TBI+SIRT1 agonist group compared with those in the TBI+vehicle group; and transmission electron microscopy showed reduced mitochondrial shrinkage and partial restoration of cristae structures in the TBI+SIRT1 agonist group compared with those in the TBI+vehicle group. Compared with the TBI+vehicle group, the TBI+SIRT1 agonist group exhibited significantly decreased MDA content ([62.72±9.20] nmol/g vs. [39.34±3.48] nmol/g), increased SOD activity ([1.95±0.23] U/mg vs. [2.48±0.14] U/mg), elevated GPX4 protein expression (0.37±0.04 vs. 0.46±0.03), and decreased HIF-1α and ACSL4 protein expressions (1.16±0.15 vs. 0.81±0.12; 1.14±0.06 vs. 1.29±0.04), with significant differences ( P<0.05). Conclusion:SIRT1 activation can exert neuroprotective effect by inhibiting HIF-1α-mediated glycolysis and reducing neuronal ferroptosis after TBI.


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