1.Shenmai Injection Reduces Cardiomyocyte Apoptosis Induced by Doxorubicin through miR-30a/Bcl-2.
Xiao-Nan ZHANG ; Yan-Yang LI ; Shi-Chao LYU ; Qiu-Jin JIA ; Jun-Ping ZHANG ; Long-Tao LIU
Chinese journal of integrative medicine 2025;31(3):240-250
OBJECTIVE:
To explore the molecular mechanism of Shenmai Injection (SMI) against doxorubicin (DOX) induced cardiomyocyte apoptosis.
METHODS:
A total of 40 specific pathogen-free (SPF) male Sprague Dawley (SD) male rats were divided into 5 groups based on the random number table, including the control group, the model group, miR-30a agomir group, SMI low-dose (SMI-L) group, and SMI high-dose (SMI-H) group, with 8 rats in each group. Except for the control group, the rats were injected weekly with DOX (2 mg/kg) in the tail vein for 4 weeks to induce myocardial injury, and were given different regimens of continuous intervention for 2 weeks. Cardiac function was detected by echocardiography and myocardial pathological changes were observed by Van Gieson (VG) staining. Myocardial injury serum markers, including creatine kinase (CK), lactate dehydrogenase (LDH), troponin T (cTnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), soluble ST2 (sST2), and growth differentiation factor-15 (GDF-15) were detected by enzyme linked immunosorbent assay (ELISA). Cardiomyocyte apoptosis was observed by terminal deoxynucleotidyl transferase-mediated biotinylated dUTP triphosphate nick end labeling (TUNEL) and transmission electron microscopy, and the expressions of target proteins and mRNA were detected by Western blot and quantitative real time polymerase chain reaction (qRT-RCR), respectively.
RESULTS:
The treatment with different doses of SMI reduced rat heart mass index and left ventricular mass index (P<0.05), significantly improved the left ventricular ejection fraction (P<0.05), decreased the levels of serum CK, LDH, cTnT, and NT-proBNP (P<0.05 or P<0.01), reduced the levels of serum sST2 and GDF-15 (P<0.05 or P<0.01), decreased the collagen volume fraction, reduced the expressions of rat myocardial type I and type III collagen (P<0.05 or P<0.01), and effectively alleviated myocardial fibrosis. And the study found that SMI promoted the expression levels of miR-30a and Bcl-2 in myocardium, and down-regulated the expression of Bax, which inhibited the activation of Caspase-3 and Caspase-9 (P<0.05 or P<0.01), and improved myocardial cell apoptosis.
CONCLUSIONS
SMI can alleviate myocardial injury and apoptosis caused by DOX, and its mechanism possibly by promoting the targeted expression of myocardial Bcl-2 protein through miR-30a.
Animals
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Myocytes, Cardiac/metabolism*
;
Apoptosis/drug effects*
;
MicroRNAs/genetics*
;
Rats, Sprague-Dawley
;
Male
;
Drugs, Chinese Herbal/administration & dosage*
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Doxorubicin/pharmacology*
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Proto-Oncogene Proteins c-bcl-2/genetics*
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Drug Combinations
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Injections
;
Rats
2.USP20 as a super-enhancer-regulated gene drives T-ALL progression via HIF1A deubiquitination.
Ling XU ; Zimu ZHANG ; Juanjuan YU ; Tongting JI ; Jia CHENG ; Xiaodong FEI ; Xinran CHU ; Yanfang TAO ; Yan XU ; Pengju YANG ; Wenyuan LIU ; Gen LI ; Yongping ZHANG ; Yan LI ; Fenli ZHANG ; Ying YANG ; Bi ZHOU ; Yumeng WU ; Zhongling WEI ; Yanling CHEN ; Jianwei WANG ; Di WU ; Xiaolu LI ; Yang YANG ; Guanghui QIAN ; Hongli YIN ; Shuiyan WU ; Shuqi ZHANG ; Dan LIU ; Jun-Jie FAN ; Lei SHI ; Xiaodong WANG ; Shaoyan HU ; Jun LU ; Jian PAN
Acta Pharmaceutica Sinica B 2025;15(9):4751-4771
T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.
4.Progress in investigating astrocyte heterogeneity after spinal cord injury based on single-cell sequencing technology.
Lei DU ; Yan-Jun ZHANG ; Tie-Feng GUO ; Lin-Zhao LUO ; Ping-Yi MA ; Jia-Ming LI ; Sheng TAN
China Journal of Orthopaedics and Traumatology 2025;38(5):544-548
In recent years, the study of single-cell transcriptome sequencing technology in the heterogeneity of astrocytes (astrocytes) after spinal cord injury (SCI) has provided new perspectives on post-traumatic nerve regeneration and repair. To provide a review on the research progress of single-cell sequencing technology in astrocytes after spinal cord injury (SCI), and to more comprehensively and deeply elaborate the application of single-cell sequencing technology in the field of astrocytes after SCI. Single-cell sequencing technology can analyse the transcriptomes of individual cells in a high-throughput manner, thus revealing fine differences in cell types and states. By using single-cell sequencing technology, the heterogeneity of astrocytes after SCI and their association with nerve regeneration and repair were revealed. In conclusion, the application of single-cell sequencing technology provides an important tool to reveal the heterogeneity of astrocytes after SCI, to further explore the mechanisms of astrocytes in SCI, and to develop intervention strategies targeting their regulatory mechanisms in order to improve the therapeutic efficacy of SCI. The discovery of changes in astrocyte transcriptome dynamics has improved researchers' understanding of spinal cord injury lesion progression and provided new insights into the treatment of spinal cord injury at different time points. To date, all of these findings need to be validated by more basic research and sufficient clinical trials. In the future, single-cell sequencing technology, through interdisciplinary collaboration with bioinformatics, computer science, tissue engineering, and clinical medicine, is expected to open a new window for the treatment of spinal cord injury.
Spinal Cord Injuries/metabolism*
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Astrocytes/cytology*
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Single-Cell Analysis/methods*
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Humans
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Animals
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Transcriptome
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Nerve Regeneration
5.Protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on a yorkshire model of brain injury after traumatic blood loss.
Xiang-Yu SONG ; Yang-Hui DONG ; Zhi-Bo JIA ; Lei-Jia CHEN ; Meng-Yi CUI ; Yan-Jun GUAN ; Bo-Yao YANG ; Si-Ce WANG ; Sheng-Feng CHEN ; Peng-Kai LI ; Heng CHEN ; Hao-Chen ZUO ; Zhan-Cheng YANG ; Wen-Jing XU ; Ya-Qun ZHAO ; Jiang PENG
Chinese Journal of Traumatology 2025;28(6):469-476
PURPOSE:
To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss.
METHODS:
This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA+, K+, and Ca2+ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance.
RESULTS:
The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA+ and K+ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca2+ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group.
CONCLUSIONS
Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals
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Perfusion/methods*
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Disease Models, Animal
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Brain Injuries/etiology*
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Swine
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Male
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Hypothermia, Induced/methods*
6.Explanation and interpretation of blood transfusion provisions for children with hematological diseases in the national health standard "Guideline for pediatric transfusion".
Ming-Yi ZHAO ; Rong HUANG ; Rong GUI ; Qing-Nan HE ; Ming-Yan HEI ; Xiao-Fan ZHU ; Jun LU ; Xiao-Jun XU ; Tian-Ming YUAN ; Rong ZHANG ; Xu WANG ; Jin-Ping LIU ; Jing WANG ; Zhi-Li SHAO ; Yong-Jian GUO ; Xin-Yin WU ; Jia-Rui CHEN ; Qi-Rong CHEN ; Jia GUO ; Ming-Hua YANG
Chinese Journal of Contemporary Pediatrics 2025;27(1):18-25
To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion is one of the most commonly used supportive treatments for children with hematological diseases. This guideline provides guidance and recommendations for blood transfusions in children with aplastic anemia, thalassemia, autoimmune hemolytic anemia, glucose-6-phosphate dehydrogenase deficiency, acute leukemia, myelodysplastic syndromes, immune thrombocytopenic purpura, and thrombotic thrombocytopenic purpura. This article presents the evidence and interpretation of the blood transfusion provisions for children with hematological diseases in the "Guideline for pediatric transfusion", aiming to assist in the understanding and implementing the blood transfusion section of this guideline.
Humans
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Child
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Hematologic Diseases/therapy*
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Blood Transfusion/standards*
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Practice Guidelines as Topic
7.Explanation and interpretation of the compilation of blood transfusion provisions for children undergoing hematopoietic stem cell transplantation in the national health standard "Guideline for pediatric transfusion".
Rong HUANG ; Qing-Nan HE ; Ming-Yan HEI ; Xiao-Fan ZHU ; Jun LU ; Xiao-Jun XU ; Tian-Ming YUAN ; Rong ZHANG ; Xu WANG ; Jin-Ping LIU ; Jing WANG ; Zhi-Li SHAO ; Ming-Yi ZHAO ; Yong-Jian GUO ; Xin-Yin WU ; Jia-Rui CHEN ; Qi-Rong CHEN ; Jia GUO ; Rong GUI ; Ming-Hua YANG
Chinese Journal of Contemporary Pediatrics 2025;27(2):139-143
To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion for children undergoing hematopoietic stem cell transplantation is highly complex and challenging. This guideline provides recommendations on transfusion thresholds and the selection of blood components for these children. This article presents the evidence and interpretation of the transfusion provisions for children undergoing hematopoietic stem cell transplantation, with the aim of enhancing the understanding and implementation of the "Guideline for pediatric transfusion".
Humans
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Hematopoietic Stem Cell Transplantation
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Child
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Blood Transfusion/standards*
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Practice Guidelines as Topic
8.Explanation and interpretation of blood transfusion provisions for critically ill and severely bleeding pediatric patients in the national health standard "Guideline for pediatric transfusion".
Rong HUANG ; Qing-Nan HE ; Ming-Yan HEI ; Ming-Hua YANG ; Xiao-Fan ZHU ; Jun LU ; Xiao-Jun XU ; Tian-Ming YUAN ; Rong ZHANG ; Xu WANG ; Jin-Ping LIU ; Jing WANG ; Zhi-Li SHAO ; Ming-Yi ZHAO ; Yong-Jian GUO ; Xin-Yin WU ; Jia-Rui CHEN ; Qi-Rong CHEN ; Jia GUO ; Rong GUI
Chinese Journal of Contemporary Pediatrics 2025;27(4):395-403
To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Critically ill children often present with anemia and have a higher demand for transfusions compared to other pediatric patients. This guideline provides guidance and recommendations for blood transfusions in cases of general critical illness, septic shock, acute brain injury, extracorporeal membrane oxygenation, non-life-threatening bleeding, and hemorrhagic shock. This article interprets the background and evidence of the blood transfusion provisions for critically ill and severely bleeding children in the "Guideline for pediatric transfusion", aiming to enhance understanding and implementation of this aspect of the guidelines. Citation:Chinese Journal of Contemporary Pediatrics, 2025, 27(4): 395-403.
Humans
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Critical Illness
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Blood Transfusion/standards*
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Child
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Hemorrhage/therapy*
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Practice Guidelines as Topic
9.Explanation and interpretation of blood transfusion provisions for children undergoing cardiac surgery in the national health standard "Guideline for pediatric transfusion".
Rong HUANG ; Qing-Nan HE ; Ming-Yan HEI ; Ming-Hua YANG ; Xiao-Fan ZHU ; Jun LU ; Xiao-Jun XU ; Tian-Ming YUAN ; Rong ZHANG ; Xu WANG ; Jing WANG ; Zhi-Li SHAO ; Ming-Yi ZHAO ; Yong-Jian GUO ; Xin-Yin WU ; Jia-Rui CHEN ; Qi-Rong CHEN ; Jia GUO ; Rong GUI ; Jin-Ping LIU
Chinese Journal of Contemporary Pediatrics 2025;27(7):778-785
To guide clinical blood transfusion practices in pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Children undergoing cardiac surgery are at high risk of bleeding, and the causes of perioperative anemia and coagulation disorders in neonates and children are complex and varied, often necessitating the transfusion of allogeneic blood components. This guideline provides direction and recommendations for specific measures in blood management for children undergoing cardiac surgery before, during, and after surgery. This article interprets the background and evidence for the formulation of the blood transfusion provisions for children undergoing cardiac surgery, hoping to facilitate the understanding and implementation of this guideline.
Humans
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Cardiac Surgical Procedures
;
Blood Transfusion/standards*
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Child
;
Practice Guidelines as Topic
10.Prognostic Value of Baseline 18F-FDG PET/CT Combined with Clinicopathological Characteristics in Diffuse Large B-Cell Lymphoma.
Tong ZHAO ; Ling YUAN ; Jia-Lin LI ; Ming ZHAO ; Yan-Mei LIN ; Jun XING ; Lan-Lan BAO
Journal of Experimental Hematology 2025;33(2):365-372
OBJECTIVE:
To investigate the prognostic value of 18 F-deoxyglucose (FDG) PET/CT metabolic parameters combined with clinicopathological features for newly diagnosed diffuse large B-cell lymphoma (DLBCL) before treatment, and analyze the relationship between tumor metabolic volume (MTV), total lesion glycolysis (TLG) and clinicopathological features.
METHODS:
The clinical data of 120 patients with pathologically confirmed DLBCL were retrospectively analyzed and 18F-FDG PET/CT was performed 1 week before treatment. The metabolic parameters including SUVmax, SUVmean, tumor-to-blood standardized uptake value ratio (TBR), tumor-to-liver standardized uptake value ratio (TLR) were obtained. MTV and TLG of the lesions were obtained with 41% of SUVmax as the threshold, and the correlation of MTV and TLG with clinicopathological features were analyzed. Progression-free survival (PFS) was calculated by follow-up for 6-153 months. Receiver operating characteristic (ROC) curve, chi-square test, Kaplan-Meier test, log-rank test and Cox proportional hazards model were used to analyze the date.
RESULTS:
The optimum cut-off values of the SUVmax, MTV, TLG, TBR and TLR for predicting tumor progression were 22.25, 256.05, 5 232.67, 12.97 and 10.60, respectively. The patients were divided into two groups according to the above cut-off values, respectively. Kaplan-Meier survival analysis showed that there were statistically significant differences in PFS between the two group (all P <0.05). The MTV and TLG values were correlated with NCCN-IPI score, Ann Arbor stage, serum lactate dehydrogenase level, and C-MYC, BCL-2, BCL-6 gene rearrangement (all P <0.05). Univariate analysis showed that NCCN-IPI score >3, C-MYC, BCL-2, BCL-6 gene rearrangement positive, SUVmax≥22.25, MTV≥256.05 cm3, TLG≥5 232.67 g and TBR≥12.97 were adverse factors for prognosis (HR: 1.949-5.759, all P <0.05). Multivariate Cox regression analysis showed that C-MYC, BCL-2 gene rearrangement positive and TLG≥5 232.67 g were all independent risk factors affecting PFS (HR: 4.660, 3.350, 4.031, all P <0.05).
CONCLUSION
The 18F-FDG PET/CT metabolic parameters SUVmax, MTV, TLG, TBR and TLR can be used as important indicators to predict PFS of DLBCL patients, and combining clinicopathological features can better predict the prognosis of patients.
Humans
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Lymphoma, Large B-Cell, Diffuse/diagnosis*
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Fluorodeoxyglucose F18
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Positron Emission Tomography Computed Tomography
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Prognosis
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Retrospective Studies
;
Male
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Female
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Middle Aged
;
Adult

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