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    Original articles
  • Original articles
    TIAN Hanke, YUE Hanlin, NAN Xiufeng, SHI Boyang, DONG Ji, ZHAO Li, WANG Hui, WANG Haoyu, PENG Ruiyun
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    Objective To investigate the effects of short-term 3.5 GHz microwave radiation on recognition memory and the gene expression profile of the prefrontal cortex of rats. Methods The behavioral performance of rats was evaluated via the novel object recognition (NOR) test,Morris water maze (MWM),and open field test (OFT) following short-term exposure to 3.5 GHz microwave radiation. Transcriptomic analysis was conducted to examine the alterations in gene expression profiles in the prefrontal cortex of rats after 6 days of 3.5 GHz microwave radiation. Key genes associated with microwave radiation induced recognition memory deficits were screened via gene interaction network analysis. The expression levels of the selected key genes were detected by real-time quantitative PCR (qPCR). Results After 6 days of 3.5 GHz microwave radiation,the recognition memory of rats significantly declined (P<0.05) while their spatial learning and memory remained unchanged,and no significant anxiety-like behaviors were observed. Compared with the Sham radiation group (Sham),1188 upregulated genes and 732 downregulated genes were detected in the prefrontal cortex of rats in the microwave radiation group (MW). Five key genes associated with microwave radiation-induced recognition memory impairment were identified by gene interaction network analysis. qPCR validation confirmed that in the prefrontal cortex,the expression levels of adrenoceptor beta 1 (Adrb1),glutamate ionotropic receptor NMDA type subunit 2b (Grin2b),Kalirin Rho guanine nucleotide exchange factor kinase (Kalrn),and myocyte enhancer factor 2c (Mef2c) were significantly upregulated (P<0.05) while that of corticotropin releasing hormone receptor 1 (Crhr1) was significantly downregulated (P<0.05). Conclusion Six days of exposure to 3.5 GHz microwave radiation can induce recognition memory impairment in rats,which may be attributed to the dysregulated gene expressions related to receptors,ion channels,and synaptic structure and function within the prefrontal cortex.
  • Original articles
    CHEN Yanzhou, LI Yunxing, ZHAGN Bowen, LI Yunqiao, LÜ Yang, FAN Tao, XU Caiping, LI Yanhua
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    Objective To investigate whether SB4,a bone morphogenetic protein 4 (BMP4) signaling agonist,can alleviate ionizing radiation-induced damage to mouse bone marrow hematopoietic stem/progenitor cells (HSPCs). Methods Mouse bone marrow lineage-negative (Lin-) cells were isolated and cultured in vitro. The optimal concentration of SB4 was determined by detecting intracellular phosphorylated mothers against decapentaplegic homolog 1/5/9 (p-SMAD1/5/9) expressions via flow cytometry and assessing cell viability via acridine orange/propidium iodide (AO/PI) staining. An in vitro ionizing radiation (IR) injury model was established by exposing Lin- cells to 3 Gy X-ray irradiation. Cells were divided into the irradiation alone group (IR-SB4 group) and the SB4 pretreatment followed by irradiation group (IR+SB4 group). On day 1 post-irradiation,flow cytometry was used to analyze the proportion and number of HSPCs and hematopoietic stem cells (HSCs). The percentage of γ-H2A histone family member X (γ-H2AX)-positive cells,levels of reactive oxygen species (ROS),and cysteinyl aspartate-specific protease 3 (caspase-3) expressions in HSCs were also determined. Real-time quantitative PCR (qPCR) was used to detect the mRNA expression levels of antioxidant genes and the anti-apoptotic genes in HSPCs from both groups. Results The BMP4 signaling agonist SB4 effectively increased the phosphorylation of SMAD1/5/9 in mouse bone marrow hematopoietic cells,and 1 μmol/L was identified as the optimal concentration for HSPCs. Compared with the IR-SB4 group,the proportions and numbers of HSPCs and HSCs were significantly larger in the IR+SB4 group,along with a lower γ-H2AX-positive rate,reduced ROS accumulation,and downregulated caspase-3 expressions in HSCs. Meanwhile,the mRNA expression levels of key genes involved in antioxidative stress and anti-apoptotic pathways in HSPCs were upregulated. Conclusion SB4 can alleviate ionizing radiation-induced damage to mouse HSPCs. The underlying mechanism is possibly associated with the activation of SMAD1/5/9 phosphorylation and the upregulation of antioxidative stress and anti-apoptotic gene expressions in HSPCs.
  • Original articles
    BAO Suya, ZHANG Mingzhe, LIU Wenhui, GUO Xinwei, XING Weiwei, GAO Bo, ZHANG An
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    Objective To investigate the regulatory effects of hypoxia combined with inflammation on microglial energy metabolism and explore the underlying synergistic mechanisms in order to provide novel targets for the prevention and treatment of high-altitude cerebral edema. Methods BV2 microglial cells were categorized into four experimental groups: control (Con),hypoxia (Hy,1% O2),lipopolysaccharide (LPS,0.1 μg/mL),and hypoxia combined with LPS (Hy-LPS). Cell viability was evaluated using the CCK-8 assay. The levels of nitric oxide (NO) and pro-inflammatory cytokines (IL-1β,IL-6,TNF-α) in the supernatant were determined via the Griess method and ELISA,respectively. Transcriptomic profiling was conducted via RNA sequencing (RNA-seq),followed by bioinformatic analyses including identification of differentially expressed genes (DEGs),Gene Ontology (GO),Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment,and Gene Set Enrichment Analysis (GSEA). Results Hy-LPS co-treatment significantly suppressed cell viability and synergistically promoted the release of NO and inflammatory cytokines compared to individual stimuli. Transcriptomic analysis revealed 2060 differentially expressed genes (DEGs) in the Hy-LPS group,including 912 up-regulated and 1148 down-regulated genes. These DEGs were prominently enriched in pathways associated with hypoxia response,inflammatory immunity,cell cycle regulation,and metabolic reprogramming,indicating a robust synergistic effect between hypoxia and inflammation at the transcriptional level. Conclusion This study sheds light on the molecular network through which hypoxia complicated with inflammation synergistically regulates microglial energy metabolism and inflammatory responses across multiple pathways,thereby providing potential targets for mechanistic research and the prevention of high-altitude cerebral edema.
  • Original articles
    WEI Zhengyang, LI Xue, ZHANG Zhaowei, ZHENG Yuanjing, WANG Yang, LIU Yuanlin, ZHANG Yi
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    Objective To establish a rat model of radiation-combined bone injury (RCBI), evaluate the therapeutic efficacy of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles (hUC-MSC-sEVs), and to investigate their role in promoting bone repair. Methods hUC-MSC-sEVs were isolated via ultracentrifugation and characterized using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting. SD rats were randomly divided into three groups:non-ionizing radiation (IR) control group (non-IR), IR model group (IR), and sEVs-treated after IR group (IR+sEV). The RCBI model was established via local irradiation with 60Co γ-rays (9.0 Gy) combined with tibial drilling injury. The IR+sEV group received local sEVs injections on days 1 and 8 post-irradiation. Bone repair was dynamically monitored by micro computed tomography (MicroCT) on days 7, 14 and 21 while bone mineral density (BMD), bone volume (BV), and bone surface/volume ratio (BS/BV) were quantitatively analyzed. On day 21, tibial specimens were harvested for hematoxylin-eosin staining and Masson’s Trichrome staining to assess the histomorphological changes. Results The isolated sEVs had a mean particle size of approximately 163.4 nm, were typically cup-shaped morphologically, and expressed specific marker proteins-tumor susceptibility gene 101 protein (TSG101) and cluster of differentiation 81(CD81). Bone repair was significantly delayed in the IR group, with large defects still visible on day 21, but was markedly enhanced in the IR+sEV group, as evidenced by new bone formation observed as early as day 14 and nearly complete defect healing by day 21. Quantitative analysis found that BMD, BV and BS/BV were all significantly superior in the IR+sEV group to those of the IR group (P<0.05). Histological examination revealed that trabecular bone structures were more intact and collagen fibers were more orderly in arrangement in the IR+sEV group. Conclusion Human umbilical cord mesenchymal stem cell-derived sEVs can significantly boost the repair of radiation-combined bone injury, which is expected to provide new insight for the biological treatment of radiation-induced bone damage.
  • Original articles
    YI Yuqing, LI Shuo, ZHANG Yang, YANG Yu, XU Rui, MA Hao, LIU Feng, XIAO Zhiyong, ZHANG Youzhi, LI Changwei
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    Objective To identify the chemical constituents of different fractions of the water extract of Chaixian Huashen decoction (CXHSD) and to evaluate the antipyretic and analgesic activities of each fraction in order to improve the extraction process. Methods The water extract of CXHSD was obtained via water reflux extraction (CXHSD-W). An alcohol-water extract was obtained via 70% ethanol reflux extraction once,followed by water reflux extraction twice (CXHSD-EW). The water extract was separated using macroporous adsorption resin into four elution fractions: water (CXHSD-00),30% ethanol (CXHSD-30),60% ethanol (CXHSD-60),and 95% ethanol (CXHSD-95). The constituents of each fraction were identified using UPLC-Q-TOF-MS technology against a self-built compound library. The contents of total flavonoids,total saponins,and total alkaloids in the water extract,the four elution fractions,and the alcohol-water extract were determined by ultraviolet spectrophotometry. The antipyretic and analgesic activities of each fraction were evaluated using a lipopolysaccharide (LPS)-induced fever model and an acetic acid-induced writhing pain model in mice. Results A total of 114 compounds were identified from the four fractions of the water extract. The main active components,including flavonoids,saponins,and alkaloids,were primarily distributed in CXHSD-30 and CXHSD-60. The results of ultraviolet spectrophotometric determination for total flavonoids,total saponins,and total alkaloids were consistent with the above findings. Animal experiments showed that CXHSD-60 significantly inhibited LPS-induced fever (P<0.001). The inhibition rate of CXHSD-30 was the highest (76.68%,P<0.001) against acetic acid-induced pain. CXHSD-EW contained higher levels of total flavonoids and total saponins than CXHSD-W while possessing superior antipyretic and analgesic activities compared to CXHSD-W. Conclusion The addition of 70% ethanol extraction in CXHSD preparation increases the extraction yield of active substances and enhances its antipyretic and analgesic activities. The optimized extraction process for this formula is determined to be ethanol extraction once,followed by water extraction twice.
  • Original articles
    QIN Haochen, LI Ning, CAO Xuelin, HE Zhen
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    The Russia-Ukraine conflict that broke out in 2022 has highlighted the distinct features of modern warfare. As a type of high-incidence injury on the battlefield, limb injuries are characterized by complexity, high risk of infection, delayed evacuation leading to aggravated conditions, increased rates of amputation, and high incidence of psychological trauma. During the treatment of limb injuries, both sides of the conflict accumulated practical experience in forward deployment of forces, application of concepts of damage control surgery, establishment of a three-dimensional evacuation system, and more effective rehabilitation. However, such problems were exposed as insufficient frontline treatment training, poor coordination in material support, and the lack of psychological treatment. This article reviews the characteristics of limb injuries, treatment regimens and takeaways from the Russia-Ukraine conflict, and conducts comparative analyses based on data on historical conflicts such as World War II and the U.S. wars in Afghanistan and Iraq in the hope of providing targeted references for the PLA to enhance its ability to manage limb injuries and improve its medical support system in high-intensity combat environments.
  • Reviews
  • Reviews
    YANG Rui, JIANG Huihui, WU Haitao
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    Brain organoids are three-dimensional in vitro models that mimic the structure and function of human neural tissue. Current methodologies involve whole-brain organoids and region-specific organoids, with emerging protocols for vascularization, immunocompetence, and multi-organ integration. As an innovative technological platform bridging basic research and clinical applications, brain organoids promise broad prospects in organ development modeling, elucidation of disease mechanisms, drug screening, and regenerative medicine, having become a vital tool for studying neurodevelopmental and neurodegenerative disorders. However, such challenges persist as limited structural complexity, incomplete functional maturation, and asynchronous development, which constrain their ability to fully recapitulate the human brain. This review summarizes recent advances in research on brain organoids, highlighting their potential in studying the development of the nervous system and associated disorders. Problems that remain to be solved are also outlined in order to provide data and references for future research in this field.
  • Reviews
    FU Wenliang, GAO Bo, ZHANG Chao
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    Post-traumatic stress disorder (PTSD) is a chronic anxiety disorder that occurs after an individual experiences a major traumatic event, characterized by the overgeneralization of fear memory, spontaneous retrieval, and impaired extinction. Recent studies have revealed that neuronal activity-induced DNA damage is not only involved in the formation and consolidation of fear memory, but also closely associated with the pathological mechanisms of PTSD due to abnormalities in its repair pathways. This review summarizes the physiological sources, molecular mechanisms, and physiological significance of neuronal DNA damage in general and the potential regulatory role of DNA double-strand breaks (DSBs) in the formation and maintenance of fear memory in particular. It also explores the underlying mechanisms by which DSBs may serve as molecular imprints of fear memory. This review also predicts the translational potential of targeting DNA damage repair pathways in PTSD treatment in the hope of providing data for developing novel therapeutic drugs for PTSD.
  • Reviews
    WANG Zejun, TAN Xiaoling
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    Cold environments make a big difference in war outcomes, as they impact health status, field survival, and combat effectiveness of military personnel who have to endure the adverse effects of environmental factors when performing military missions in cold environments. Cold exposures can compromise the combat and emergency capabilities of military operators and cause direct harm to health. Therefore, improving cold acclimatization is essential to the health status and combat effectiveness of military personnel stationed amid cold exposures. This review summarizes advances in research on cold acclimatization, especially assessment approaches and acclimatization-promoting strategies, in the hope of helping upgrade cold acclimatization training, enhancing cold tolerance, and reduce the incidence of cold injuries.
  • Reviews
    HE Yuruo, LI Xiaoli, HOU Wenjie, NIU Xiaolin
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    The pathogenesis of cardiovascular diseases is complex, and myocardial cell death is a leading factor behind disease progression and adverse outcomes. Programmed cell death (PCD), the primary execution form of myocardial cell death, has such key subtypes as ferroptosis, apoptosis, necroptosis, autophagy, and pyroptosis. In recent years, the regulatory mechanisms and pathophysiological roles of various PCD subtypes in cardiovascular diseases have been gradually clarified, opening up new spheres and providing potential targets for the targeted therapy of these diseases. This review summarizes the key molecular mechanisms and crosstalk regulatory relationships of different PCD subtypes in cardiovascular diseases, and analyzes the synergistic and antagonistic effects among various pathways in the hope of providing data for the precise diagnosis and optimization of therapeutic regimens for cardiovascular diseases.
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