1.Ablation of macrophage transcriptional factor FoxO1 protects against ischemia-reperfusion injury-induced acute kidney injury.
Yao HE ; Xue YANG ; Chenyu ZHANG ; Min DENG ; Bin TU ; Qian LIU ; Jiaying CAI ; Ying ZHANG ; Li SU ; Zhiwen YANG ; Hongfeng XU ; Zhongyuan ZHENG ; Qun MA ; Xi WANG ; Xuejun LI ; Linlin LI ; Long ZHANG ; Yongzhuo HUANG ; Lu TIE
Acta Pharmaceutica Sinica B 2025;15(6):3107-3124
Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.
2.Analysis of potential changes in symptom characteristics of breast cancer patients before and after chemotherapy and nursing countermeasures
Wanqin TIE ; Xi ZHANG ; Yongqi WANG ; Yang XU ; Xuefeng CHEN ; Lu PAN ; Siyu CHEN
Chinese Journal of Nursing 2025;60(2):193-200
Objective To explore the time-varying pattern of potential symptoms in breast cancer patient before and after chemotherapy,and further analyze its influencing factors,aims to provide reference for clinical nursing practice.Methods 233 cases of breast cancer in a tertiary A hospital in Ningxia from June to October,2023 were selected as the research subjects.By the general information questionnaire and the Chinese version of Anderson Symptom Assessment Scale,the potential change of symptoms of breast cancer patients undergoing chemotherapy 1-3 days before the first chemotherapy(T1,233 cases)and 7-14 days after the third or fourth chemotherapy(T2,225 cases)was analyzed.Results 225 cases of breast cancer patients completed 2 surveys,and their symptom characteristics before and after chemotherapy can be divided into 2 categories:a high symptom troubled group and a low symptom troubled group.The high-symptom troubled group has strong stability,and the probability of maintaining the original group is 85.20%,while the low-symptom troubled group is more inclined to change to the high-symptom troubled group,and the transition probability is 26.60%.Logistic regression analysis showed that the mass was located on the left side,and the patients who obtained disease knowledge mainly through the Internet were more likely to change from the high symptom troubled group to the low symptom troubled group,while the patients who were employed,with unsatisfactory sleep at night,and never exercised were more likely to change from the low symptom troubled group to the high symptom troubled group.Conclusion The symptoms of breast cancer patients before and after chemotherapy are heterogeneous.Patients who are on the job,have unsatisfied sleep at night and never exercise are more likely to change from the low-symptom troubled group to the high-symptom troubled group,which suggests that medical staff should identify potential high-risk groups at an early stage,and make full use of the predictive function of symptom characteristics to carry out individualized management based on the dynamic monitoring of symptoms according to different types of population characteristics,so as to reduce the burden of symptoms and improve their quality of life.
3.Primary intraosseous synovial sarcoma:a case report and literature review
Wen ZHAO ; Wei-Jun QIAN ; Li LI ; Yan-Min WANG ; Peng-Hui SU ; Chao-Xin ZHANG ; Liang XU ; Tie-Cheng WU ; Jun-Qi LIU ; Ya-Jun WANG
Medical Journal of Chinese People's Liberation Army 2025;50(11):1419-1425
Objective To report a case of tibial synovial sarcoma and review relevant literature to enhance understanding of this disease.Methods The clinical data of a patient with tibial synovial sarcoma treated at Kaifeng Central Hospital were retrospectively analyzed.A literature search was conducted in domestic and international databases,including China National Knowledge Infrastructure(CNKI),Wanfang Data,PubMed,Web of Science,and Embase,up to July 2024.Relevant literature was comprehensively reviewed to summarize the imaging and pathological characteristics,treatment,and prognosis of synovial sarcoma.Results A 29-year-old female patient was admitted with left lower extremity pain.X-ray examination revealed a proximal tibia space-occupying lesion suggestive of malignancy,and a mid-tibial space-occupying lesion considered benign.Contrast-enhanced computed tomography(CT)and plain magnetic resonance imaging(MRI)of the proximal tibial lesion also suggested malignancy.Ultrasound-guided biopsy of the proximal tibial tumor revealed a poorly differentiated malignant tumor.Immunohistochemistry results indicated monophasic synovial sarcoma,requiring genetic testing for definitive diagnosis.The patient underwent wide resection of the proximal left tibial malignancy with tumor-type artificial joint replacement,combined with curettage and bone cement filling for the left mid-tibial lesion under anesthesia.Postoperative pathology of space-occupying lesions in the proximal tibia confirmed monophasic synovial sarcoma,and fluorescence in situ hybridization(FISH)demonstrated a rupture of the synovial sarcoma translocation gene(SYT)(i.e.,SS18 positive).There was no recurrence or metastasis found in the patient during the reexamination 6 months after postoperative chemotherapy.As of July 2024,15 cases of genetically confirmed primary intraosseous synovial sarcoma have been reported internationally.Symptoms included pain and swelling,with a medical history of 1-2 years.The X-ray and CT findings showed osteolytic destruction with bone cortical discontinuity.In 13 cases,the intraosseous masses extended to the extraosseous area;in 2 cases,punctate calcifications were detected within the masses.Plain MRI scan showed iso-signal or hypo-signal on T1WI and hyper-signal,iso-signal,and hypo-signal on fat-suppressed T2WI,and enhanced MRI scan demonstrated heterogeneous enhancement.Pathological examination showed spindle-shaped cells under microscopy.Immunohistochemistry results showed positive epithelial membrane antigen(EMA),broad-spectrum cytokeratin(AE1/AE3),Ewing's sarcoma marker(CD99),and transducin-like enhancer of Split 1(TLE1).Twelve patients underwent surgical treatment;6 patients received adjuvant chemotherapy after surgery,of whom 4 developed local recurrence or distant metastasis at initial diagnosis,and 3 died during follow-up.Among the 6 patients who did not receive adjuvant chemotherapy,3 suffered from recurrence or distant metastasis.Conclusions Primary intraosseous synovial sarcoma is a rare malignant tumor with non-specific clinical manifestations.Imaging features typically include osteolytic destruction and intraosseous masses extending extraosseously,suggesting an intraosseous origin.Pathology and immunohistochemistry aid diagnosis,but definitive confirmation relies on further genetic testing.At present,the main treatment regimens for synovial sarcoma involve comprehensive therapies such as surgery and adjuvant chemotherapy,and the prognosis of patients is poor.
4.Exogenous administration of zinc chloride improves lung ischemia/reperfusion injury in rats.
Shu-Yuan WANG ; Jun-Peng XU ; Yuan CHENG ; Man HUANG ; Si-An CHEN ; Zhuo-Lun LI ; Qi-Hao ZHANG ; Yong-Yue DAI ; Li-Yi YOU ; Wan-Tie WANG
Acta Physiologica Sinica 2025;77(5):811-819
The aim of this study was to investigate the contribution of lung zinc ions to pathogenesis of lung ischemia/reperfusion (I/R) injury in rats. Male Sprague Dawley (SD) rats were randomly divided into control group, lung I/R group (I/R group), lung I/R + low-dose zinc chloride group (LZnCl2+I/R group), lung I/R + high-dose ZnCl2 group (HZnCl2+I/R group), lung I/R + medium-dose ZnCl2 group (MZnCl2+I/R group) and TPEN+MZnCl2+I/R group (n = 8 in each group). Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the concentration of zinc ions in lung tissue. The degree of lung tissue injury was analyzed by observing HE staining, alveolar damage index, lung wet/dry weight ratio and lung tissue gross changes. TUNEL staining was used to detect cellular apoptosis in lung tissue. Western blot and RT-qPCR were used to determine the protein expression levels of caspase-3 and ZIP8, as well as the mRNA expression levels of zinc transporters (ZIP, ZNT) in lung tissue. The mitochondrial membrane potential (MMP) of lung tissue was detected by JC-1 MMP detection kit. The results showed that, compared with the control group, the lung tissue damage, lung wet/dry weight ratio and alveolar damage index were significantly increased in the I/R group. And in the lung tissue, the concentration of Zn2+ was markedly decreased, while the cleaved caspase-3/caspase-3 ratio and apoptotic levels were significantly increased. The expression levels of ZIP8 mRNA and protein were down-regulated significantly, while the mRNA expression of other zinc transporters remained unchanged. There was also a significant decrease in MMP. Compared with the I/R group, both MZnCl2+I/R group and HZnCl2+I/R group exhibited significantly reduced lung tissue injury, lung wet/dry weight ratio and alveolar damage index, increased Zn2+ concentration, decreased ratio of cleaved caspase-3/caspase-3 and apoptosis, and up-regulated expression levels of ZIP8 mRNA and protein. In addition, the MMP was significantly increased in the lung tissue. Zn2+ chelating agent TPEN reversed the above-mentioned protective effects of medium-dose ZnCl2 on the lung tissue in the I/R group. The aforementioned results suggest that exogenous administration of ZnCl2 can improve lung I/R injury in rats.
Animals
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Reperfusion Injury/pathology*
;
Male
;
Rats, Sprague-Dawley
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Rats
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Chlorides/administration & dosage*
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Lung/pathology*
;
Zinc Compounds/administration & dosage*
;
Apoptosis/drug effects*
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Caspase 3/metabolism*
;
Cation Transport Proteins/metabolism*
5.Potential profile analysis of symptoms and quality of life of patients with early breast cancer undergoing postoperative chemotherapy
Wanqin TIE ; Xi ZHANG ; Lu PAN ; Siyu CHEN ; Yang XU ; Xuefeng CHEN
Chinese Journal of Practical Nursing 2025;41(5):332-339
Objective:To explore the potential categories of symptom characteristics of early breast cancer patients undergoing postoperative chemotherapy, analyze the differences of symptoms among different categories of patients, and compare their quality of life according to different categories.Methods:This was a cross-sectional study. From January to June 2023, 240 patients with early breast cancer who received chemotherapy after surgery in General Hospital of Ningxia Medical University were selected by convenience sampling. They were investigated by general information questionnaire, Memory Symptom Assessment Scale, and Functional Assessment of Caner Therapy-Breast Cancer. Mplus 8.3 was used to carry out potential profile analysis and identify the potential categories of symptom characteristics of early breast cancer patients undergoing postoperative chemotherapy. Binary Logistic regression analysis was used to determine the influencing factors of symptom characteristics. SPSS 26.0 software was used to compare the differences in quality of life scores of patients undergoing postoperative chemotherapy for different categories of early breast cancer.Results:Totally 233 valid questionnaires were ultimately collected, with an age of 50.85 ± 8.09. There were two potential categories of postoperative chemotherapy patients with early breast cancer: low symptom troubled group (159 cases, 68.2%) and high symptom troubled group (74 cases, 31.8%). The quality of life score of the high symptom distress group was (76.84 ± 13.15) points, which was significantly lower than (89.56 ± 11.29) points of the low symptom distress group, and the difference was statistically significant ( t=7.18, P<0.01). Logistic regression analysis showed that patients with early breast cancer who had financial burden after postoperative chemotherapy were more likely to belong to the group with high symptoms [ OR (95% CI) was 3.028 (1.434-6.394), P<0.01]. Postoperative chemotherapy patients with early breast cancer who had satisfactory sleep at night are more likely to belong to the group with low symptoms [ OR(95% CI) was 0.446 (0.217-0.920), P<0.05]. Conclusions:There is population heterogeneity in the symptom characteristics of patients with early breast cancer undergoing postoperative chemotherapy. and economic burden and night sleep are the influencing factors of symptom distress categories of breast cancer patients. It is suggested that medical staff should give individualized and targeted intervention measures centered on patients′ needs according to different types of population characteristics, so as to reduce the symptom burden and improve their quality of life.
6.Analysis of potential changes in symptom characteristics of breast cancer patients before and after chemotherapy and nursing countermeasures
Wanqin TIE ; Xi ZHANG ; Yongqi WANG ; Yang XU ; Xuefeng CHEN ; Lu PAN ; Siyu CHEN
Chinese Journal of Nursing 2025;60(2):193-200
Objective To explore the time-varying pattern of potential symptoms in breast cancer patient before and after chemotherapy,and further analyze its influencing factors,aims to provide reference for clinical nursing practice.Methods 233 cases of breast cancer in a tertiary A hospital in Ningxia from June to October,2023 were selected as the research subjects.By the general information questionnaire and the Chinese version of Anderson Symptom Assessment Scale,the potential change of symptoms of breast cancer patients undergoing chemotherapy 1-3 days before the first chemotherapy(T1,233 cases)and 7-14 days after the third or fourth chemotherapy(T2,225 cases)was analyzed.Results 225 cases of breast cancer patients completed 2 surveys,and their symptom characteristics before and after chemotherapy can be divided into 2 categories:a high symptom troubled group and a low symptom troubled group.The high-symptom troubled group has strong stability,and the probability of maintaining the original group is 85.20%,while the low-symptom troubled group is more inclined to change to the high-symptom troubled group,and the transition probability is 26.60%.Logistic regression analysis showed that the mass was located on the left side,and the patients who obtained disease knowledge mainly through the Internet were more likely to change from the high symptom troubled group to the low symptom troubled group,while the patients who were employed,with unsatisfactory sleep at night,and never exercised were more likely to change from the low symptom troubled group to the high symptom troubled group.Conclusion The symptoms of breast cancer patients before and after chemotherapy are heterogeneous.Patients who are on the job,have unsatisfied sleep at night and never exercise are more likely to change from the low-symptom troubled group to the high-symptom troubled group,which suggests that medical staff should identify potential high-risk groups at an early stage,and make full use of the predictive function of symptom characteristics to carry out individualized management based on the dynamic monitoring of symptoms according to different types of population characteristics,so as to reduce the burden of symptoms and improve their quality of life.
7.Potential profile analysis of symptoms and quality of life of patients with early breast cancer undergoing postoperative chemotherapy
Wanqin TIE ; Xi ZHANG ; Lu PAN ; Siyu CHEN ; Yang XU ; Xuefeng CHEN
Chinese Journal of Practical Nursing 2025;41(5):332-339
Objective:To explore the potential categories of symptom characteristics of early breast cancer patients undergoing postoperative chemotherapy, analyze the differences of symptoms among different categories of patients, and compare their quality of life according to different categories.Methods:This was a cross-sectional study. From January to June 2023, 240 patients with early breast cancer who received chemotherapy after surgery in General Hospital of Ningxia Medical University were selected by convenience sampling. They were investigated by general information questionnaire, Memory Symptom Assessment Scale, and Functional Assessment of Caner Therapy-Breast Cancer. Mplus 8.3 was used to carry out potential profile analysis and identify the potential categories of symptom characteristics of early breast cancer patients undergoing postoperative chemotherapy. Binary Logistic regression analysis was used to determine the influencing factors of symptom characteristics. SPSS 26.0 software was used to compare the differences in quality of life scores of patients undergoing postoperative chemotherapy for different categories of early breast cancer.Results:Totally 233 valid questionnaires were ultimately collected, with an age of 50.85 ± 8.09. There were two potential categories of postoperative chemotherapy patients with early breast cancer: low symptom troubled group (159 cases, 68.2%) and high symptom troubled group (74 cases, 31.8%). The quality of life score of the high symptom distress group was (76.84 ± 13.15) points, which was significantly lower than (89.56 ± 11.29) points of the low symptom distress group, and the difference was statistically significant ( t=7.18, P<0.01). Logistic regression analysis showed that patients with early breast cancer who had financial burden after postoperative chemotherapy were more likely to belong to the group with high symptoms [ OR (95% CI) was 3.028 (1.434-6.394), P<0.01]. Postoperative chemotherapy patients with early breast cancer who had satisfactory sleep at night are more likely to belong to the group with low symptoms [ OR(95% CI) was 0.446 (0.217-0.920), P<0.05]. Conclusions:There is population heterogeneity in the symptom characteristics of patients with early breast cancer undergoing postoperative chemotherapy. and economic burden and night sleep are the influencing factors of symptom distress categories of breast cancer patients. It is suggested that medical staff should give individualized and targeted intervention measures centered on patients′ needs according to different types of population characteristics, so as to reduce the symptom burden and improve their quality of life.
8.Study on the preservation effects of the amputated forelimb by machine perfusion at physiological temperature
Sheng-Feng CHEN ; Bo-Yao YANG ; Tie-Yuan ZHANG ; Xiang-Yu SONG ; Zhi-Bo JIA ; Lei-Jia CHEN ; Meng-Yi CUI ; Wen-Jing XU ; Jiang PENG
Chinese Journal of Traumatology 2024;27(2):114-120
Purpose::Ischemia and hypoxia are the main factors limiting limb replantation and transplantation. Static cold storage (SCS), a common preservation method for tissues and organs, can only prolong limb ischemia time to 4 - 6 h. The normothermic machine perfusion (NMP) is a promising method for the preservation of tissues and organs, which can extend the preservation time in vitro by providing continuous oxygen and nutrients. This study aimed to evaluate the difference in the efficacy of the 2 limb preservation methods. Methods::The 6 forelimbs from beagle dogs were divided into 2 groups. In the SCS group ( n = 3), the limbs were preserved in a sterile refrigerator at 4 °C for 24 h, and in the NMP group ( n = 3), the perfusate prepared with autologous blood was used for the oxygenated machine perfusion at physiological temperature for 24 h, and the solution was changed every 6 h. The effects of limb storage were evaluated by weight gain, perfusate biochemical analysis, enzyme-linked immunosorbent assay, and histological analysis. All statistical analyses and graphs were performed using GraphPad Prism 9.0 one-way or two-way analysis of variance. The p value of less than 0.05 was considered to indicate statistical significance. Results::In the NMP group, the weight gained percentage was 11.72% ± 4.06%; the hypoxia-inducible factor-1α contents showed no significant changes; the shape of muscle fibers was normal; the gap between muscle fibers slightly increased, showing the intercellular distance of (30.19 ± 2.83) μm; and the vascular α-smooth muscle actin (α-SMA) contents were lower than those in the normal blood vessels. The creatine kinase level in the perfusate of the NMP group increased from the beginning of perfusion, decreased after each perfusate change, and remained stable at the end of perfusion showing a peak level of 4097.6 U/L. The lactate dehydrogenase level of the NMP group increased near the end of perfusion and reached the peak level of 374.4 U/L. In the SCS group, the percentage of weight gain was 0.18% ± 0.10%, and the contents of hypoxia-inducible factor-1α increased gradually and reached the maximum level of (164.85 ± 20.75) pg/mL at the end of the experiment. The muscle fibers lost their normal shape and the gap between muscle fibers increased, showing an intercellular distance of (41.66 ± 5.38) μm. The contents of vascular α-SMA were much lower in the SCS group as compared to normal blood vessels.Conclusions::NMP caused lesser muscle damage and contained more vascular α-SMA as compared to SCS. This study demonstrated that NMP of the amputated limb with perfusate solution based on autologous blood could maintain the physiological activities of the limb for at least 24 h.
9.Relationship between lymphocyte subsets and prognosis of patients with viral pneumonia complicated with ARDS
Zhen XU ; Zhao WANG ; Haisheng ZHANG ; Yongxin TIE ; Xinming XU
Chinese Journal of Immunology 2024;40(10):2146-2149,2157
Objective:To investigate correlation between neutrophil lymphocyte ratio(NLR),IL-6 and lymphocyte subsets and prognosis of viral pneumonia complicated with acute respiratory distress syndrome(ARDS).Methods:A total of 98 patients with viral pneumonia complicated with ARDS admitted to Xinxiang Central Hospital/the Fourth Clinical College from May 2017 to June 2019 were selected,NLR,IL-6 and lymphocyte subsets expressions in patients with different severity were analyzed.Correlation between NLR,IL-6 and lymphocyte subsets levels in prognosis of viral pneumonia complicated with ARDS was analyzed by Pearson correlation.Logistc regression was used to analyze prognostic risk factors of viral pneumonia complicated with ARDS.Results:With aggravation of viral pneumonia complicated with ARDS,NLR and IL-6 levels were significantly increased(P<0.05),while CD3+T,CD4+T and CD19+T cells levels were significantly decreased(P<0.05).Pearson correlation analysis results showed that NLR and IL-6 were positively correlated with prognosis of viral pneumonia complicated with ARDS(P<0.05),while CD3+T,CD4+T,CD19+T and CD8+T cells were negatively correlated with prognosis of ARDS with viral pneumonia(P<0.05).Multivariate Logistic analysis showed that NLR,IL-6,CD3+T and CD19+T cells were risk factors for viral pneumonia complicated with ARDS(P<0.05).Conclusion:Serum NLR,IL-6,CD3+T and CD19+T cells are closely related to severity and prognosis of patients with viral pneumonia complicated with ARDS.
10.Therapeutic potential of exosome derived from remote ischemic conditioning in alleviating neurologic dysfunction after cardiac arrest in a rat model
Heng ZHAI ; Jihui WANG ; Xi CHEN ; Yang ZHANG ; Shuqun HU ; Jun WANG ; Yigen PENG ; Ningjun ZHAO ; Xianliang YAN ; Chenglei SU ; Tie XU
Chinese Journal of Emergency Medicine 2024;33(7):991-998
Objective:To investigate the therapeutic effect of exosomes derived from remote ischemic conditioning on neurological dysfunction after cardiopulmonary resuscitation in a rat model of cardiac arrest and the relationship with glycocalyx protection.Methods:Exosomes were isolated from the blood of healthy adult male Sprague-Dawley rats using ultracentrifugation after undergoing remote ischemic conditioning for use as intervention drugs. Nanoparticle tracking analysis technology was used for exosome detection. Thirty-six adult male Sprague-Dawley rats were randomly assigned to 3 groups ( n=12 each) :Sham group, Control group and Exosome group. Cardiac arrest was induced by asphyxia for 7 min in the Control and Exosome groups. Placebo or exosomes (1×10 10 Particles) were infused intravenously at 5 min after the rats had returned of spontaneous circulation. Neuropsychological deficit score (NDS), open field test, Y maze and Morris water maze were used to assess neurological outcomes. The levels of plasma Hyaluronic acid (HA) and syndecan-1 (Sdc-1) were detected by Elisa. The expression levels of matrix metalloproteinase-2/9 (MMP-2/9) in hippocampal CA1 region were detected by Western blot. Results:After undergoing remote ischemic conditioning, the plasma levels of exosomes were elevated in rats compared to normal rats. Compared with the control group, the behavioral experiment of rats in the exosomes group were significantly improved, as evidenced by an increase in horizontal locomotor distance (5.86±2.89 vs. 17.53±5.51, P< 0.05), an increase in the correct rate of spontaneous alternation (13.29±15.07 vs. 42.63±10.25, P< 0.05), and a shortening of avoidance latency (25.83±8.54 vs. 13.49±4.55, P< 0.05). Plasma HA and Sdc-1 levels were significantly lower 24 h after resuscitation (HA: 26.34±9.83 vs. 14.84±6.26, P< 0.05; Sdc-1: 0.05±0.03 vs. 0.02±0.02, P<0.05), along with significantly lower MMP-2/9 levels in hippocampal tissue. Conclusions:Exosomes extracted from the plasma of rats undergoing remote ischemic conditioning can improve neurological dysfunction after cardiac arrest in rats, and the mechanism may be related to the inhibition of metalloproteinases and the reduction of endothelial glycocalyx degradation.

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