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  • Expert review
    JIANG Yugang, SHEN Hui, DU Peng, GUO Changjiang, DU Shuguang, JIANG Zhanwei
    Military Medical Sciences. 2024, 48(8): 561-564. https://doi.org/10.7644/j.issn.1674-9960.2024.08.001
    The Dietary Ration for Military Personnel(GJB 826C—2022)is a new standard formulated after revision of the national military standard - Dietary Ration for Soldiers (GJB826B—2010). The major changes included that:①The daily standards of the ration for different types of stoveswere merged and integrated, and special requirements for food ration and food quality of personnel in special positions such as pilots, divers and those in direct contact with nuclear materials were specified;②The food structure was optimized. The daily standards of ration for grain, animal food, especially livestock and poultry meat were lowered while those for fruit and milk were increased.The requirements for the supply of whole grains were elevated while the proportions of lean meat, beef and mutton, seafood and other animal foods were detailed;③The new daily standards for nuts were added.The new standard could better meet the practical needsof actual combat, underscored dietary quality, and proved to be more user-friendly and practical. It is of great significance for improving the dietary nutrition of troops, creating a new dietary pattern to improve combat effectiveness, constructing a support system for joint military operations, and enhancing the military supply capabilities in China.
  • Reviews
    PEI Yihao, CHEN Siyao, SU Yuyin, MAO Yiming, LI Ben
    Military Medical Sciences. 2024, 48(9): 708-714. https://doi.org/10.7644/j.issn.1674-9960.2024.09.012
    Mesenchymal stem cells have emerged as a promising cell therapy for anti-tumor research due to their homing properties,low immunogenicity,anti-angiogenic activity,anti-inflammatory properties,and paracrine effects. Paclitaxel has been clinically used for over thirty years in the treatment of various tumors such as ovarian cancer,lung cancer,and breast cancer. However,the broad-spectrum anti-tumor properties of paclitaxel are not possessed by the aforementioned cell therapies. Moreover,its adverse reactions,including peripheral neuropathy,bone marrow suppression,and gastrointestinal reactions,have long plagued cancer patients. In recent years,many studies have focused on combining cell therapy with chemotherapy to achieve better treatment outcomes,giving rise to a new drug delivery system that utilizes mesenchymal stem cells as carriers for delivering chemotherapeutic drugs. This review summarizes the research progress in MSC-based drug delivery systems for paclitaxel.
  • Original articles
    CI Weihao, LI Yating, XU Litao, CHEN Chen, YANG Xiaoming, REN Guangming
    Military Medical Sciences. 2024, 48(5): 334-339. https://doi.org/10.7644/j.issn.1674-9960.2024.05.03
    Objective To investigate the therapeutic effect and mechanism of NLRP3 inflammasome inhibitor-dapansutrile (OLT1177)-against acute radiation lung injury. Methods Mice were divided into the control group, OLT1177 injection group, irradiation group, and irradiation + OLT1177 injection group. A single dose of 22 Gy whole-lung 60Co radiation was used to establish a model of acute radiation lung injury. After 6 h of radiation, OLT1177 (100 mg/kg, once daily) was administered intraperitoneally. After 14 consecutive days of administration, lung tissues were collected and weighed while the lung coefficient was calculated. Hematoxylin-eosin(HE) staining and F4/80 immunohistochemical staining were used to observe the pathological changes and inflammatory cell infiltration in lung tissues. Real-time quantitative PCR (qPCR) was used to detect the transcription levels of NLRP3, IL-1β, and other mRNAs in lung tissues. Serum cytokines such as TNF-α and IL-6 were measured by cytometric bead array(CBA). The activation of Caspase-1 and IL-18 was detected by Western blotting. Results Radiation caused acute inflammation in the lung tissues of mice, manifested as edema in the lung tissues and destruction of the alveolar structure, increased macrophage infiltration, and elevated expressions of inflammatory genes NLRP3, IL-1β, TNF-α, and IL-6 in the lung tissues and higher serum levels of TNF-α, IL-6. Treatment with OLT1177 significantly improved the above symptoms induced by radiation. OLT1177 inhibited the activation of NLRP3 inflammasome downstream Caspase-1 and IL-18 induced by radiation. Conclusion OLT1177 can significantly alleviate acute radiation lung injury in mice, which may be due to its inhibition of NLRP3 inflammasome activation induced by radiation.
  • Reviews
    XIAO Lan, WANG Chuang, LIU Jia, LIU Luyao, GUO Lei, TANG Li
    Military Medical Sciences. 2024, 48(4): 294-302. https://doi.org/10.7644/j.issn.1674-9960.2024.04.008
    Abrin, the most lethal plant-derived toxin known today, has attracted widespread attention from both the International Chemical Weapon Convention and the Biological and Toxin Weapons Convention. There is an urgent demand for the development of efficient detection and detoxification countermeasures against Abrin to adress its potential threats to human health and public safety. This review, based on clustering analysis of literature and on knowledge of the structures of various subtypes of Abrin, provides an overview of the analysis and detection techniques, the mechanism of toxicity, and detoxification countermeasures against Abrin. It concludes with an examination of the challenges and emerging trends in this field. The main analysis and detection techniques of Abrin include affinity-based analysis, physico-chemical-based analysis, and activity-based detection techniques. The challenges and developments in this field are also outlined. There is a pressing need to establish sensitive, specific, and accurate methods of measurement that are tailored to the structure and activity of Abrin in order to precisely assess and mitigate the toxin threat. Unfortunately, no effective antidotes have been deployed so far, with medical treatments confined to symptomatic care. Research and development of neutralizing antibodies remain stands as the most promising strategy for counteracting Abrin intoxication.
  • Reviews
    BAO Ke, SONG Lun, HANG Xin
    Military Medical Sciences. 2024, 48(8): 630-635. https://doi.org/10.7644/j.issn.1674-9960.2024.08.012
    As an important frontier for research, neuroscience and brain-inspired intelligence have become priorities of research globally. Noninvasive neuromodulation and neurofunctional evaluation techniques have become important tools for neuroscience research and clinical applications. Noninvasive neuromodulation techniques represented by transcranial magnetic stimulation have proved to promise good prospects in the treatment and rehabilitation of a variety of neurological diseases. This paper reviews the main effects of PBM in the treatment of brain diseases and cognitive impairments.
  • Reviews
    ZHANG Na, QI Fengxue
    Military Medical Sciences. 2024, 48(4): 303-310. https://doi.org/10.7644/j.issn.1674-9960.2024.04.009
    Cognitive function enhancement refers to the process of enhancing one or more core component of human brain cognition. Transcranial direct current stimulation (tDCS), as a non-invasive neuromodulation technique, can regulate brain cortical excitability, synaptic plasticity and brain networks functional connection. tDCS can be used to modulate cognitive function components, such as perception, working memory, attention, motor learning and decision-making. This article reviews the neural and physiological mechanism of tDCS over cerebral cortex modulating neural activity and the research progress in human cognitive performance of single tDCS on perception, working memory, attention, motor learning, decision-making and language of healthy individuals in order to provide reference for researchers.
  • Reviews
    ZHANG Jieyuan, DUAN Zhaoxia, LI Bingcang
    Military Medical Sciences. 2024, 48(4): 311-316. https://doi.org/10.7644/j.issn.1674-9960.2024.04.010
    The active denial system (ADS) is a millimeter wave electromagnetic directional energy non-lethal technology and the only microwave device against humans. Microwave radiation can cause damage to multiple systems in the human body, including the nervous, circulatory, immune, and reproductive systems. This article outlines the development, basic structure, and equipment of ADS, characteristics and mechanisms of medical injuries due to ADS, medical injury efficacy of ADS in terms of effects on the human body, determinants and skin depth. The precautions against and medical treatment of ADS-caused symptoms are briefly described.
  • Reviews
    YAN Jun, LIN Bencheng, LIU Xiaohua, XI Zhuge
    Military Medical Sciences. 2024, 48(10): 791-798. https://doi.org/10.7644/j.issn.1674-9960.2024.10.010
    Cognitive ability assessment and cognitive enhancement techniques play an important role in maintaining and improving human cognitive function, psychological and emotional stability, and in enhancing work efficiency.This paper begins by introducing the theory of cognitive ability, influencing factors and cognitive assessment methods before summarizing the latest progress in current cognitive enhancement strategies and technological paths and analyzing their prospects of applications in order to provide reference for the development and application of personnel cognitive assessment and cognitive enhancement technology in the future.
  • Review
    BAN Chunli, JIANG Beier, WANG Ruoxi, XIANG Yu-jie, HE Ying
    Military Medical Sciences. 2024, 48(5): 395-400. https://doi.org/10.7644/j.issn.1674-9960.2024.05.012
    Chronic fatigue syndrome (CFS) is a chronic, multi-system disease manifested as prolonged fatigue and often accompanied by somatization symptoms that include muscle pain and sleep disorders, which is why CFS impacts patients’ life and health. However, the etiology of CFS remains unknown. There is no specific treatment as well. Treatments currently available mostly use specific medicines to treat specific symptoms or assist clinicians by such means as cognitive-behavioral therapies or nutritional support. While on long-distance voyages, the Navy soldiers spend a long time in relatively closed environments under high pressure, which is likely to result in physical and mental fatigue and even CFS. This paper reviews the causes, current level of diagnosis, as well as the treatment and prevention of CFS in order to contribute to the health and operational capability of Navy soldiers.
  • Reviews
    DING Ruochen, SHU Zhan, YANG Jian
    Military Medical Sciences. 2024, 48(3): 230-235. https://doi.org/10.7644/j.issn.1674-9960.2024.03.011
    Hypothermia is one of the complications of the body under cold environments and trauma, which poses a serious threat to human lives. This paper reviews the technical properties and the development of protective and rewarming equipment, which is of referential value for the design and selection of rewarming equipment for hypothermia of different degrees.
  • Original articles
    QIAO Zizhi, ZHANG Xuewen, XING Shuang, SHU Hui, LI Yuqing, WANG Hua, YU Zuyin
    Military Medical Sciences. 2024, 48(3): 172-179. https://doi.org/10.7644/j.issn.1674-9960.2024.03.003
    Objective To establish a mouse model with an inducible deletion of PIKfyve genes throughout the body and hematopoietic system and explore the impact of PIKfyve on immune homeostasis. Methods LoxP sites were inserted at both ends of exon 6 of the PIKfyve gene to establish PIKfyve+/flox mice. PIKfyve+/flox mice were cross-bred to produce PIKfyveflox/flox mice. PIKfyveflox/flox mice were cross-bred with UBC-Cre/ERT2 mice to obtain PIKfyve+/flox, UBC-Cre/ERT2 mice and PIKfyveflox/flox, UBC-Cre/ERT2 mice, the target mice. Genotyping was performed using tail gene PCR, and deletion efficiency was identified post-induction via real-time quantitative PCR (qPCR) and Western blotting. The proportion and number of mature immune cells in peripheral blood, bone marrow, and spleens were observed and compared between the knockout mice and control mice. A similar breeding strategy was adopted to introduce PIKfyveflox/flox,MX1-Cre mice to confirm the aforementioned results in a distinct mouse model. Results Successful generation of PIKfyveflox/flox, UBC-Cre/ERT2 mice was confirmed based on mouse breeding and tail gene PCR. After induction, a significant decrease in PIKfyve mRNA and protein contents in the knockout mice indicated the establishment of a proper model. Peripheral blood analysis revealed a significant reduction in white blood cells, lymphocytes, neutrophils, and monocytes in the PIKfyve-deficient mice. Flow cytometry demonstrated an overall decrease in the proportions of B cells and NK cells, with a significant increase in T cells and neutrophils, while the overall number trended down. Results from PIKfyveflox/flox,MX1-Cre mice were consistent with those of PIKfyveflox/flox, UBC-Cre/ERT2 mice. Conclusion A workable PIKfyve knockout mouse model has been established, suggesting that PIKfyve can regulate the number and proportions of mature immune cells while making a difference to immune homeostasis.
  • Original articles
    WANG Qiong, HONG Jian, GUO Jin, DUAN Junzhao, DING Kexin, TAI Fumin, ZHENG Xiaofei, GE Changhui
    Military Medical Sciences. 2024, 48(4): 241-250. https://doi.org/10.7644/j.issn.1674-9960.2024.04.001
    Objective To investigate the mechanism underlying gasdermin E (GSDME)-mediated pyroptosis in radiation-induced intestinal injury and to find out whether gasdermin (GSDM) family members regulate pyroptosis through similar signaling pathways. Methods Human normal colon epithelial cells(NCM460) and human colon cancer cells(HT-29) were exposed to radiation of different doses and durations before pyroptosis indicators were evaluated by observing pyroptotic bubbles,cell survival,and the cleavage of pyroptosis execution proteins. HT-29 cells overexpressing GSDME were subjected to radiation,followed by enrichment analysis of pyroptosis-related differentially expressed genes using RNA-seq. Results Radiation induced substantial pyroptosis in NCM460 cells. Overexpression of GSDME in HT-29 cells resulted in substantial radiation-induced pyroptosis.The pyroptosis state of human intestinal cells was simulated in the HT-29 model cell line. Overexpressions of GSDME-N and GSDMD-N resulted in the expression of more than 50% of the differentially expressed genes in the pyroptosis state. Sequencing analysis showed that the genes in the pyroptosis state were mainly overrepresented in immune response,inflammatory response,and Rap1 signaling pathway. Conclusion GSDME activation can mediate radiation-induced pyroptosis by producing GSDME-N fragments. GSDM family members participate in pyroptosis in a similar mode of regulation. Furthermore,radiation-induced activation of GSDME/D may regulate pyroptosis through immune response,inflammatory response,and Rap1 signaling pathway.
  • Original articles
    PENG Mei, HUANG Ye, ZHENG Li, LI Junhui, ZHANG Hongxing
    Military Medical Sciences. 2024, 48(7): 530-536. https://doi.org/10.7644/j.issn.1674-9960.2024.07.008
    Objective To assess causal associations between specific gut microbiota and different types of cancer by using the two-sample Mendelian randomization (MR) analysis method. Methods On the basis of summary statistics of gut microbiota from a genome-wide association study (GWAS) conducted in German population (n=8956), single nucleotide polymorphisms (SNPs) that were significantly associated with 430 gut microbiota features were extracted as instrumental variables (IVs). Summary statistics from the GWAS of 17 types of cancer were used as outcomes. Two-sample MR analysis was used to explore the causal relationship between gut microbiota and pan-cancer, where the analysis results were dominated by inverse variance weighting. Meanwhile, sensitivity analyse of heterogeneity and horizontal pleiotropy test were done to keep the stability of results. Results The genetic susceptibility of 17 gut microbiota features was causally associated with the occurrence and development of 11 different types of cancer,respectively. Conclusion By exploring the causal relationship between different gut microbiota features and pan-cancer,this study has found a potential causal relationship between specific gut microbiota features and cancer, and these gut microbiota may become new biomarkers to provide new ideas for cancer prevention, early screening, and treatment.
  • Original articles
    LIU Yichen, YAN Dongfei, LI Zhixin, MAO Yingchun, LI Zhihui, DONG Guofu, WANG Changzhen
    Military Medical Sciences. 2024, 48(7): 481-486. https://doi.org/10.7644/j.issn.1674-9960.2024.07.001
    Objective To investigate the role of Kelch-like- epichlorohydrin-associated protein1/nuclear factor erythroid-derived factor-2-related factor 2 (Keap1-Nrf2) and nuclear factor-κB(NF-κB) signaling pathways in sepsis-associated encephalopathy(SAE). Methods Male C57BL/6J mice of SPF were randomly divided into four groups (n=10): the control group and LPS 6 h, 24 h and 48 h groups. The behavioral changes of the mice were assessed based on their general conditions and open field test(OFT). ELISA was used to measure the levels of pro-inflammatory cytokines in mouse serum, and the antioxidant capacity assay kit to examine antioxidant activity in brain tissues of mice. Real-time quantitative PCR(qPCR) was adopted to detect the mRNA levels of toll-like receptor4 (Tlr4), NF-κB, Keap1 and Nrf2 in the hippocampus, and to determine protein expressions of NF-κB、Nrf2、Keap1 and Tlr4 with Western blotting. Results Compared to the control group, the serum concentrations of interleukin 6 (IL-6) in lipopolysaccharide(LPS) groups increased at 6 h, and reached the peak at 24 h and 48 h (P<0.01). The levels of serum interleukin 18 (IL-18) in the LPS groups increased significantly at 6 h and 24 h (P<0.01) but there was no statistically significant difference compared with the 48h group. The results indicated the activity of superoxide dismutase(SOD) and glutathione(GSH) in brain tissues in LPS groups increased(P<0.01). OFT results showed the time spent in the center of the open field, the distance covered around the center, and total distance covered by mice in LPS groups were significantly reduced (P<0.01),except for the time spent in the center of the open field in the LPS 24 h group. The mRNA expressions of Tlr4 and (LPS 6 h, 48 h) NF-κB in the hippocampus tissue of mice in LPS groups were elevated (P<0.05), so were the mRNA expressions of Keap1 and Nrf2 in LPS 6 h group. Additionally, the protein expressions of NF-κB, Keap1 and Tlr4 increased in LPS groups, so did the protein expression of Nrf2 in LPS 24 h and 48 h groups(P<0.05). Conclusion Keap1-Nrf2 and NF-κB signaling pathways may play a certain role in SAE.;
  • Original articles
    GAO Yuting, ZHANG Biao, JIA Yali, WANG Haiyang, FAN Tao, XI Jiafei, YUE Wen, ZENG Quan, ZHOU Junnian
    Military Medical Sciences. 2024, 48(8): 586-593. https://doi.org/10.7644/j.issn.1674-9960.2024.08.005
    Objective To construct HEK 293T cells that express tardigrade Dsup protein fused with green fluorescent protein copGFP in order to study the effect of Dsup protein on proliferation of HEK 293T cells. Methods The CRISPR/Cas9 gene knock-in system was constructed. The target gene fragments of Dsup, copGFP, EF1α and puromycin were amplified by PCR and inserted into pAAVS1-SFFV to construct the fusion vector of Dsup and copGFP, which was known as pAAVS1-SFFV-Dsup-copGFP-EF1α-Puro. pAAVS1-SFFV-Dsup-copGFP-EF1α-Puro and pAAVS1-CRISPR-Cas9 vector were co-transfected into HEK 293T cells before Dsup gene was inserted into the AAVS1 region of HEK 293T cells via homologous recombination. The HEK 293T cells expressing Dsup gene were obtained following puromycin selection, flow cytometry sorting and genome identification. The expression of Dsup at mRNA and protein levels and proliferation-related genes (MCM2, MCM4, PCNA, Ki-67) were examined to investigate the effects of Dsup gene on the proliferation of HEK 293T-Dsup-copGFP cells. Results The pAAVS1-SFFV-Dsup-copGFP-EF1α-Puro recombinant vector was constructed, and the HEK 293T-Dsup-copGFP cells with Dsup gene inserted in the AAVS1 region were obtained, where both Dsup mRNA and protein were expressed. The cell proliferation rate of HEK 293T-Dsup-copGFP was higher than that of HEK 293T-Control-copGFP(P<0.001). Further investigation revealed that the expressions of Ki-67 and MCM4 protein in HEK 293T-Dsup-copGFP were significantly higher than in the control group, indicating that the knock in of Dsup gene might enhance the proliferation ability of human cells by promoting the expression of Ki-67 and MCM4 protein. Conclusion A gene editing vector is constructed, and stable cell line HEK 293T-Dsup-copGFP for Dsup fusion expression with copGFP is established. The expression of Dsup gene in HEK 293T cells can promote cell proliferation, possibly by upregulating the expressions of Ki-67 and MCM4 protein.
  • Original articles
    LI Daguang, TIAN Deqiao
    Military Medical Sciences. 2024, 48(4): 288-293. https://doi.org/10.7644/j.issn.1674-9960.2024.04.007
    Preventing bioweapons is an important component of biosecurity, and the Biosecurity Law of the People's Republic of China has a chapter devoted to "Preventing Biological Terrorism and the Threat of Bioweapons". A good knowledge of the history plays a positive role in effective protection against bioweapons. This article analyzes history of bioweapons based on books and literature that have been published in order to provide reference for professionals in the sphere of biosecurity.
  • Reviews
    HAN Siman, CHEN Yifei, SHEN Donglai, WANG Yizheng
    Military Medical Sciences. 2024, 48(3): 236-240. https://doi.org/10.7644/j.issn.1674-9960.2024.03.012
    Radiation-induced brain injury is a severe brain injury caused by ionizing radiation to normal brain tissue. It is manifested as cognitive dysfunction, decreased learning and memory ability and can even lead to dementia. The treatment of existing drugs for radiation-induced brain injury are far from effective with poor prognosis. Ionizing radiation induces pathological activation of astrocytes, which aggravates the process of radiation-induced brain injury by inducing neuroinflammation and destroying the blood-brain barrier. Here we review the physiological and pathological functions of astrocytes, then analyze the pathological changes and cellular mechanisms of astrocytes involved in radiation-induced brain injury. Furthermore, the therapeutic potential of astrocytes in radiation-induced brain injury is discussed, which is expected to provide reference for finding more approaches to radiation-induced brain injury and exploring new therapeutic targets and methods.
  • Reviews
    CHEN Honglei, REN Peng, LI Yunfeng
    Military Medical Sciences. 2024, 48(7): 554-560. https://doi.org/10.7644/j.issn.1674-9960.2024.07.012
    Major depressive disorder (MDD) is a mental disease characterized by persistent depression, lack of interest and impaired cognitive function. Antidepressants currently availablein clinic are effective but accompanied by many adverse reactions, such as slow onset, cognitive impairment, sexual dysfunction.Therefore, novel antidepressant targets and therapeutic strategies with rapid onset of action, cognitive enhancement and low adverse effects have increasingly become a promising sphere of research. Studies have suggested that Sigma-1 receptor plays an important role in combating depression by regulating inflammatory response, excitation /inhibition balance and endoplasmic reticulum homeostasis.Moreover, Sigma-1 receptor agonists may have the advantages of rapid onset, enhanced cognition and low adverse reactions, which show good prospects for the development of new antidepressants. This article reviews the research progress related to Sigma1 receptors in the regulatory mechanism and treatments for depression in the hopes of providing new insights into new antidepressants.
  • Original articles
    YU Fei, SU Fang, CHEN Shan, LU Tingting, ZHANG Huibian, TIAN Dawei, YAO Qin
    Military Medical Sciences. 2024, 48(3): 161-165. https://doi.org/10.7644/j.issn.1674-9960.2024.03.001
    Objective To study the influence of night vision goggles (NVG) on depth perception and the role of depth perception training in improving depth perception. Methods The naked and NVG depth perception of 113 healthy male volunteers was tested using facilities for depth perception measurement and NVGs in a dark room. The measurements were repeated three times. Differential analysis was conducted of naked and NVG depth perception.Variance analysis was used to determine the influence of the number of times of measurement on the results of depth perception. Results The results of 3-time measurements of naked depth perception were (62.55±64.70)mm, (39.83±42.55)mm and (39.50±42.89)mm respectively, compared with (98.29±83.74)mm, (63.22±60.29)mm and (65.50±69.69)mm for NVG depth perception. The results of 3-time measurements of NVG depth perception were significantly worse(P<0.05). The results of the second and third measurements were significantly improved compared with the first one(P<0.05), involving both the naked and NVG depth perception. Conclusion Depth perception with NVGs is significantly worse than naked perception, but it can be enhanced after experience is gained. Pilots need to experience depth perception with NVGs and their depth perception should be evaluated before night flight missions.
  • Original articles
    MENG Renjie, LUO Nan, JIN Yuan, YUE Junjie, WANG Boqian, GAO Yuanming
    Military Medical Sciences. 2024, 48(3): 213-218. https://doi.org/10.7644/j.issn.1674-9960.2024.03.008
    Objective To differentiate between highly genetically similar bacteria, such as Escherichia coli and Shigella spp. using deep learning techniques in order to contribute to clinical diagnosis and epidemic prevention. Methods A convolutional neural network(CNN) was proposed based on transfer learning with a large-scale pre-trained protein language model, which could enable rapid and accurate identification of bacterial strains at the genus level. To validate the reliability of this model, whole-genome data on related bacteria was retrieved from the National Center for Biotechnology Information(NCBI) in the United States before the full-genome protein sequences of highly genetically similar strains of Escherichia coli and Shigella spp. were selected as experimental samples. Results With this method,genus-level classification accuracies of 97.13% and 95.56% were made available respectively during classification experiments on 2960 strains with high assembly quality and 4945 strains with low assembly quality, which outperformed the other methods currently available. Conclusion This study demonstrates the reliability and potential of deep learning-based methods for differentiation of bacterial types. By integrating self-supervised pre-training techniques with transfer learning, this approach can capture high-dimensional feature differences that are not easily discernible or statistically analyzable by humans. Furthermore, this method exhibits broad applicability, as it requires lower assembly completeness of the bacterial genome sequences used.
  • Original articles
    LIU Hanjing, LI Shuo, WANG Bikun, WANG Zengming, ZHANG Shanning, LIU Yuanyuan, ZHAO Chunying, ZHENG Aiping
    Military Medical Sciences. 2024, 48(3): 195-201. https://doi.org/10.7644/j.issn.1674-9960.2024.03.006
    Objective To explore the antidepressant effect and mechanism of an aqueous extract of Morinda officinalis How. Methods Thirty-six SD rats were randomly assigned to the control group, model group, the fluoxetine hydrochloride group and low, medium, and high dose groups of aqueous extract of Morinda officinalis How. A chronic unpredictable stress method was used to create a model which was administered for 28 days. Behavioral analysis was conducted to evaluate the antidepressant effect of the aqueous extract of Morinda officinalis How. Hematoxylin-eosin staining was used to observe the morphology of hippocampal neurons in rats while immunohistochemistry staining was adopted to detect the expression levels of inflammasome NLRP3 and microglial marker protein Iba-1. Western blotting was used to detect the expression levels of BDNF, PI3K, Akt, and GSK3β. Results After medication, the behavior and physiology of depressed rats were significantly improved. The Sugar-water preference ratio was significantly increased(P<0.01) and the forced swimming immobility time was significantly shortened (P<0.05). The morphology of neurons in the CA3 area of the rat hippocampus was improved. The protein expressions of NLRP3 and Iba-1 were reduced. The expression levels of BDNF, PI3K, p-PI3K, Akt, and p-Akt proteins were up-regulated while the those of GSK3β and p-GSK3β proteins were down-regulated. Conclusion The aqueous extract of Morinda officinalis How can improve the depression-like behavior induced by chronic stimulation in rats, and its antidepressant mechanism may be related to improving neuronal morphology, inhibiting hippocampal inflammatory response and regulating BDNF/PI3K/Akt/GSK3β pathway.
  • Original articles
    ZHAO Lu, FENG Ye, ZHANG Sen, CHEN Yuehong, LI Jing, LI Yuchang, JIANG Tao
    Military Medical Sciences. 2024, 48(7): 509-515. https://doi.org/10.7644/j.issn.1674-9960.2024.07.005
    Objective To identify stable reference genes for a comparison of the transcription levels of target host genes under viral infection in order to provide data for studies on interactions between the host and the influenza virus. Methods Reverse transcription quantitative real-time PCR (RT-qPCR) was performed to detect the relative expression levels of six candidate reference genes, including glyceraldehyde 3-phosphate dehydrogenase(GAPDH), β-actin, 18S RNA, β; 2-microglobulin (B2M), ubiquitin-conjugating enzyme E2D2(UBE2D2), and ribosomal protein L37A(RPL37A) in classical cell models (A549 cells and THP-1 cells) under different conditions. The stability of the reference genes was evaluated using such methods as BestKeeper, GeNorm, NormFinder, and comparative ΔCt method. Results The stability of reference genes varied depending on conditions. When such experimental factors as influenza virus infection and immune activation were taken into consideration, β-actin and GAPDH were identified as the most stable reference genes in A549 cells and THP-1 cells, followed by UBE2D2 and B2M. Conclusion The optimal reference genes in A549 cells and THP-1 cells under influenza virus infection or after being treated with interferons or LPS have been identified, which is of referential value for studying the mechanisms of viral infections.;
  • Original articles
    MA Junpeng, WEN Juyi, DU Peng, ZHAO Xiangfei
    Military Medical Sciences. 2024, 48(4): 273-280. https://doi.org/10.7644/j.issn.1674-9960.2024.04.005
    Objective To investigate the inhibitory effect of anlotinib combined with anti-PD1 antibody on a colon cancer mouse model, and to explore its possible mechanismfor remodeling the immune system and tumor microenvironment. Methods A BALB/c mouse model was established with colon cancer cells CT26, and the mice were divided randomly into four groups: the control group, the anlotinib group, anti-PD1 antibody group and anlotinib combined with anti-PD1 antibody group, with 6 mice in each. During the experiment, tumor volumes were measured every 2 days using a vernier caliper. After the experiment (on day 14), the weight of the tumors of mice in each group was measured. Flow cytometry was used to detect changes in the number of immune infiltrating cells in tumor tissues, including CD4+T cells, CD8+T cells, monocytic myeloid-derived suppressor cells (M-MDSCs), granulocytic myeloid-derived suppressor cells (G-MDSCs), and M2-type tumor-associated macrophages (M2-TAM). Furthermore, ELISA was employed to detect the levels of vascular endothelial growth factor (VEGF), interferon-γ (IFN-γ), interleukin-17 (IL-17), and IL-10 in the serum of mice. Results Compared with the control group, the other three groups showed a decrease in the volume and weight of transplanted tumors in mice (P<0.05), as well as decreased levels of cytokines VEGF, IL-10 (P<0.05), and IL-17 (P<0.01). Additionally, there was an increase in the level of IFN-γ (P<0.05). In terms of the number of immune infiltrating cells, the number of M-MDSCs decreased in each treatment group compared to the control group, but without statistically significant difference (P>0.05). In the combined group, the number of M2-type TAMs decreased compared to the control group and the anti-PD-1 antibody group (P<0.05). Furthermore, flow cytometry results indicated that compared to the control group, the other three groups showed an increase in the number of CD8+T cells in mice (P<0.05). The number of CD4+T cells decreased slightly compared to the other groups, but the statistically significant difference was only observed when compared to the anlotinib group (P<0.05). Conclusion The combination of anlotinib and anti-PD1 antibody may regulate the levels of cytokines VEGF, IFN-γ, IL-10, and IL-17, thereby influencing the number of immunosuppressive cells in the tumor microenvironment. The tumor microenvironment and immunity can also be improved, thus significantly inhibiting the growth of mouse colonic transplant tumors.
  • Reviews
    GAO Xinlong, HE Ying, WU Wenhui, WAN Yu, SUN Ying, LIU Lina, JIANG Beier
    Military Medical Sciences. 2024, 48(8): 625-629. https://doi.org/10.7644/j.issn.1674-9960.2024.08.011
    Sleep disorders are characterized by abnormal amounts of sleep and unusual behavior during sleep. Long-term sleep disorders can lead to the disruption of normal social functioning or neurological conditions. In recent years, the role of sound wave therapy in improving sleep quality has attracted much attention. This article aims to review the research progress related to the role of sound wave therapy in enhancing sleep quality, cognitive function, and alleviating fatigue in patients with sleep disorders in hopes of contributing to clinical applications.
  • Reviews
    CHEN Yan, MA Li, SUN Lijun, LI Xiumin
    Military Medical Sciences. 2024, 48(8): 620-624. https://doi.org/10.7644/j.issn.1674-9960.2024.08.010
    Pain is one of the five vital signs, and the leading complication of war trauma, so analgesia is critical to combat casualty care. The U.S. Tactical Combat Casualty Care guidelines have defined the battlefield graded analgesic strategies. This paper reviews the assessment of pain grade of war wounds, involving the preliminary evaluation according to categories and conditions of trauma, and the quantitative evaluation according to subjective feeling and objective index monitoring. The analgesic strategies are analyzed, involving such as analgesic drugs local anesthetics, non-steroidal analgesics, opioids, N-methyl-D-aspartate receptor antagonists, and such analgesic techniques as regional nerve block, nerve radiofrequency, nerve ablation and spinal cord electrical stimulation technology. This review is expected to provide a useful reference for improving pain management and war injury treatment in China’s army.
  • Original articles
    WANG Zhenyu, ZHANG Hongmei, JING Lin, YAN Qi, TANG Jixiang, GE Qirui
    Military Medical Sciences. 2024, 48(10): 778-785. https://doi.org/10.7644/j.issn.1674-9960.2024.10.008
    Objective To evaluate both the causal relationship between plasma metabolites and the risk of knee osteoarthritis (KOA) and the potential mediating or masking effect of immune cells using Mendelian randomization (MR) systems. Methods The GWAS data on 1400 plasma metabolites, 731 immune cell traits and KOA was retrieved from the genome-wide association study (GWAS) database. Two-way MR analysis was used to evaluate the causal relationship between plasma metabolism and KOA. Two-step mediation MR analysis was conducted to evaluate immune cell traits that might have mediating or masking effects. Results After sensitivity analysis and screening, 65 plasma metabolites and 35 immune cell traits were found to have causal relationships with KOA (P<; 0.05). Mediation analysis found that CD45RA+ CD28- CD8br %CD8br had a mediating effect in the causal relationship between three metabolites (2-hydroxyhippurate, X-07765, X-23739) and the risk of KOA. 2-hydroxyhippurate (salicylic acid) exerted a masking effect, and the effect ratio was 0.0412. Results A variety of plasma metabolites and immune cell traits are causally related to KOA, which should not be regarded as a simple degenerative joint disease. The protective effect of salicylic acid against KOA may be weakened by its role in inducing the differentiation of Treg cells, which is worthy of more studies.
  • Original articles
    SONG Qiuyue, CHEN Yuan, JIA Shuyu, YING Xiaomin, HE Zhen
    Military Medical Sciences. 2024, 48(7): 516-523. https://doi.org/10.7644/j.issn.1674-9960.2024.07.006
    Objective To develop multimodal joint cognitive representations for the research of visual cognitive activities of the brain, enhance the classification performance of visual information cognitive representations, predict brain electroencephalogram (EEG) responses from visual image features, and decode visual images from EEG signals. Methods A architecture combining a multimodal variational autoencoder network with the Mixture of Product Experts (MoPoE) approach and with a style generation adversarial network based on adaptive discriminator augmentation (StyleGAN2-ADA) was used for facilitating the learning of cognitive representations and the encoding and decoding of EEG signals. This framework not only catered to classification tasks but also enabled cross-modal generation of images and EEG data. Results The present study integrated features from different modalities, enhancing the classification accuracy of cognitive representations of visual information. By aligning the feature spaces of diverse modalities into a cohesive latent space, cross-modal generation tasks were made possible. The cross-modal generation results of EEG and images, derived from this unified latent space, outperformed the one-way mapping methods that involved transition from one modality to another employed in previous research. Conclusion This study effectively integrates and aligns information from various modalities, enabling the classification performance of joint cognitive representations beyond any single modality. Moreover, the study demonstrates superior outcomes in cross-modal generation tasks compared to modality-specific unidirectional mappings, which is expected to offer a new line of thought for the effective unified encoding and decoding modeling of visual cognitive information in the brain.
  • Original articles
    LYU Yadi, FU Yesheng, ZHANG Lingqiang
    Military Medical Sciences. 2024, 48(4): 260-266. https://doi.org/10.7644/j.issn.1674-9960.2024.04.003
    Objective To construct a mouse model with conditional knockout of deubiquitinase Otulin gene in the endocardium and to analyze the phenotype of the model. Methods A model of mice with endocardium-specific conditional Otulin gene knockout was constructed with the Cre-loxP technique. The genotypes of Otulin gene knockout mice were determined by using polymerase chain reaction (PCR). Data on the reproduction of the knockout mice was statistically analyzed and the growth and development of the offspring were observed. The Cardiac function of mice was monitored by ultrasound and the changes of cellular components in blood were measured by a fully automatic hematology analyzer. Hematoxylin-eosin(HE) staining was used to analyze the pathological changes in all the tissues and organs of the offspring. Results An endocardium-specific Otulin gene knockout mouse model was established. The conditional knockout mice could grow and reproduce normally and the percentage of genotypes of their offspring conformed to Mende′s law. Compared with littermate control mice,the conditional knockout mice had smaller body size,lighter weight,significantly enlarged spleens and spiking inflammatory cells in blood. In addition,the tricuspid valve defect and cardiac function were attenuated. Conclusion A mouse model of endocardium-specific Otulin gene knockout has been constructed. These mice show impaired cardiac function and obvious inflammatory response.
  • Original articles
    TONG Fan, LIU Mingqiu, DING Yi, WU Zhengsheng, CUI Chunping
    Military Medical Sciences. 2024, 48(3): 166-171. https://doi.org/10.7644/j.issn.1674-9960.2024.03.002
    Objective To investigate the impact of uroporphyrinogen Ⅲ synthase (UROS) on bone loss induced by weightlessness. Methods Eight male C57BL/6J mice aged 9 weeks were randomly assigned to a control group and a tail suspension group,with four mice in each. Following a 28-day period of tail suspension,the hind limbs of the mice underwent micro-CT and mechanical testing,respectively. A microgravity osteoclast model was established using the cell cyclotron device (RCCS). Changes in osteoclast differentiation activity induced by microgravity were assessed via real-time quantitative PCR (qPCR) and tartrate-resistant acid phosphatase (TRAP) staining. Additionally,alterations in UROS expression levels were detected using qPCR and Western blotting analysis. The protein expression of UROS was also determined via Western blotting. A UROS knockout RAW264.7 stable strain was generated. qPCR and TRAP staining were employed to confirm the downregulation of osteoclast differentiation activity upon UROS deficiency. Results After hindlimb unloading in mice,a marked decrease in bone mass was observed in the bone tissue,which was accompanied by a pronounced upregulation of UROS protein expression. Upon exposure to microgravity,osteoclasts exhibited an upregulation of UROS protein expression,along with increased levels of osteoclast differentiation markers including matrix metalloproteinase 9 (MMP-9) and tartrate-resistant acid phosphatase (TRAP). Knockdown of UROS significantly downregulated the expression levels of osteoclast differentiation-related markers,indicating its crucial role in osteoclast differentiation and bone metabolism. Conclusion Under weightlessness stress,the expression level of UROS in osteoclasts is upregulated,leading to enhanced osteoclast activity and an imbalance between bone resorption and bone formation,with bone resorption exceeding bone formation,which ultimately results in bone loss.
  • Original articles
    REN Boyuan, LI Qiang, JIN Jiayan, WANG Yichen, DING Hongfan, JIN Jide
    Military Medical Sciences. 2024, 48(5): 325-333. https://doi.org/10.7644/j.issn.1674-9960.2024.05.002
    Objective To evaluate the therapeutic effect of poloxamer hydrogel loaded with exosomes derived from human dental pulp stem cells genetically modified with human hepatocyte growth factor against radiation skin injuries. Methods Human dental pulp stem cells derived exosomes (DPSC-Exo) and hepatocyte growth factor modified DPSC-Exo (HGF-DPSC-Exo) were extracted via ultracentrifugation separation, identified in terms of particle size and morphology, and analyzed separately by means of nanoparticle tracking analysis and scanning electron microscopy (SEM), while exosome marker proteins were determined by Western blot. Then, the effect of exosomes on radiation-damaged skin cells was assessed. The poloxamer hydrogel was prepared and its safety was evaluated with CCK-8. A mouse model of injury combined with radiation injury was established, and the therapeutic effect of hydrogel loaded with exosomes was determined based on wound size, HE and Masson staining. Furthermore, the underlining therapeutic mechanism was explored with Tunnel assay, malondialdehyde content and peroxidase activity. Results The diameter exosomes ranged from 30 to 150 nm and their morphology was a disc-shaped vesicle under SEM. Moreover, CD9, CD63 and TSG101 were expressed. The results of cellular experiments showed that exosomes significantly promoted the proliferation and migration of radiation-damaged skin keratinocytes and fibroblasts, and reduced their apoptosis. HGF modification enhanced the healing effect of exosomes. Poloxamer hydrogel showed good temperature-sensitive properties and biocompatibility. The results of animal experiments showed that exosomes significantly accelerated the healing of radiation-combined injuries in mice, inhibited inflammatory infiltration and mitigated collagen deposition in the wound. Interestingly, the healing effect in the group treated with hydrogel loaded with exosomes was the best. The underlining mechanism was possibly related to promotion of cell proliferation and inhibition of apoptosis and oxidative stress. Conclusion A novel poloxamer hydrogel loaded HGF-DPSC-Exo has been prepared and its therapeutic effect against radiation combined injury has been proved, thus providing a new strategy for the treatment of radiation skin injury in clinic.
  • Original articles
    CUI Yanan, ZOU Pengfei, GONG Wei, WANG Yuli, GAO Chunsheng, YANG Yang, YANG Meiyan
    Military Medical Sciences. 2024, 48(5): 369-375. https://doi.org/10.7644/j.issn.1674-9960.2024.05.008
    Objective To study the properties and antimicrobial activity of the novel self-assembled antimicrobial peptide (AMP) CR-16, and to provide experimental evidence for the treatment of bacterial infections. Methods CR-16 was designed and synthesized based on the structure of antimicrobial peptides BuforinⅡ and LfcinB. Dynamic light scattering (DLS), transmission electron microscopy (TEM), and X-ray diffraction (XRD) were used to characterize CR-16. Based on the results of critical micelle concentration (CMC), the self-assembled properties of CR-16 were investigated using atomic force microscopy (AFM) and circular dichroism (CD). The minimum inhibitory concentration (MIC) was used to study the inhibitory effect of CR-16 while transmission electron microscopy (TEM) was adopted to observe the interactions between CR-16 and the outer membrane of bacteria. Results AMP CR-16 was prepared as self-assemblies, which were regularly spherical in shape and stable in activity. CR-16 could inhibit both the growth of Escherichia coli and, more importantly, the growth of NDM-1-producing carbapenem-resistant Escherichia coli, promising good prospects in treating infections caused by antibiotic-resistant bacteria. Conclusion CR-16 can be self-assembled and deliver antibacterial effects against Escherichia coli.
  • Original articles
    SONG Yabin, ZHAO Xiaodong, WANG Baogang, ZHAO Jin
    Military Medical Sciences. 2024, 48(7): 543-548. https://doi.org/10.7644/j.issn.1674-9960.2024.07.010
    In recent years, public health events caused by severe infectious diseases had a profound impact on human health,economic and social development. Drug stockpiling for infectious disease prevention and treatment is of great significance in improving the ability to respond to public health events.However, the drug stockpiling system of China for infectious disease prevention and treatment still needs to be improved. Based on the investigation and comparison of the current status of drug stockpiling for infectious disease prevention and treatment between China and the United States, this article proposes some suggestions according to China's specific circumstances for reference.
  • Original articles
    DUAN Min, YANG Zhe, LIU Ying, WANG Yongyi, YE Yumeng, HAO Yanhui, ZUO Hongyan, LI Yang
    Military Medical Sciences. 2024, 48(9): 641-649. https://doi.org/10.7644/j.issn.1674-9960.2024.09.001
    Objective To investigate the effects of 0.5 Gy 60Co γ-ray irradiation on intestinal tissue injury and intestinal microflora in mice. Methods C57BL/6N mice were irradiated with 0.5 Gy 60Co γ-ray at 1 d, 3 d, 7 d and 14 d after irradiation. Jejunum tissues were fixed and frozen, and feces were frozen. Hematoxylin-eosin staining was used to observe the pathological injury to jejunum after irradiation, ki67 immunohistochemical staining was adopted to detect the proliferation of jejunum crypt cells, and TdT-mediated dUTP nick end labeling was employed to detect the apoptosis of jejunum crypt cells. The expressions of TNF-α, IL-1β, IL-6 and IL-10 cytokines in small intestines were detected via radioimmunoassay. The changes of intestinal flora in mice after irradiation were analyzed by metagenomic sequencing, and LEfSe analysis and ROC analysis were used to screen the bacteria with significant differences. Results After 0.5 Gy 60Co γ-ray irradiation, the proliferative cells of the jejunal crypt were significantly decreased at 1 d after irradiation(P<0.05), while the apoptotic cells were significantly increased at 1 and 3 d after irradiation (P<0.01). The expression of TNF-α at 7 and 14 d after irradiation, that of IL-1β at 1,3,7 and 14 d after irradiation and that of IL-6 at 3,7 and 14 d after irradiation were significantly increased (P<0.05), while the expression of IL-10 at 7 and 14 d after irradiation was significantly decreased (P<0.05). After 0.5 Gy 60Co γ-ray irradiation, intestinal flora composition changed significantly at phylum, genus and species levels, and Lactobacillus murinus, Lactobacillus johnsonii, Alistipes-unclassified, Mucispirillum schaedleri underwent the most significant changes and had higher LDA scores. Conclusion The whole body irradiation of 0.5 Gy 60Co γ-ray can cause intestinal tissue damage and change the composition of intestinal flora in mice.
  • Original articles
    HAN Luobing, SUN Shiyang, ZHAO Yu, YU Gang, SU Ruibin, ZHENG Zhibing, LI Song
    Military Medical Sciences. 2024, 48(10): 767-777. https://doi.org/10.7644/j.issn.1674-9960.2024.10.007
    Objective To discover 5-HT2A receptor antagonist molecules with novel structures and explore their structure-activity relationship through structure- and mechanism-based drug design, synthesis and activity evaluation. Methods The way in which pimovanserin interacted with 5-HT2A receptor was analyzed via molecular docking, molecular dynamics simulation and binding free energy calculations.Based on the results of this study, the 5-HT2A receptor antagonist target compounds with novel structures were designed using pimovanserin as the lead molecule. According to the structures of target compounds, corresponding synthetic routes were designed. The heterocyclic methylamine intermediates were obtained by reductive amination or reduction reaction from heterocyclic formaldehyde or heterocyclic methanonitrile before being reacted with 4-(4-fluorobenzylamino)-1-methylpiperidine to obtain the target compounds using CDI urea synthesis method. The inhibitory activity of the target compounds against 5-HT2A receptor was tested at the cellular level, and the anti-hallucinogenic effects of the target compounds were tested in the mouse head twitch response model. Results Twelvenovel compounds were synthesized and their structures were confirmed by HR-MS, 1H-NMR and 13C-NMR. The results of the activity assay showed that compounds 6a, 6c and 6d exhibited better 5-HT2Areceptor inhibitoryactivity with IC50 values of 120, 152 and 285 nmol/L, respectively while compounds 6c and 6d exhibited better anti-hallucinogenic activity in mice with inhibition rates of 97.0% and 82.9% (10 mg/kg), respectively. Results The novel compound 6c and 6d have shown strong 5-HT2A receptor inhibitoryactivity and anti-hallucinogenic activity and deserve more research. Structure-activity relationship analyses of target compounds indicate that the repulsion of the heterocyclic ring with basic N atoms and the accommodation of the heterocyclic ring without basic N atoms by the side extended pocket of the 5-HT2A receptor could significantly affect the ex vivo and in vivo effects of antagonists.
  • Reviews
    ZHU Wei, WU Haowei, XU Donggang
    Military Medical Sciences. 2024, 48(9): 701-707. https://doi.org/10.7644/j.issn.1674-9960.2024.09.011
    Cognitive dysfunction, predominantly a consequence of neurodegenerative disorders, is a burgeoning health issue. Odor molecules have the unique ability to circumvent the blood-brain barrier through the olfactory pathway, exerting a direct influence on cognitive-related brain regions including the entorhinal cortex, hippocampus, and amygdala, without transiting through the thalamus. These olfactory molecules, mostly sourced from natural plant essential oils, are characterized by significant volatility, minimal adverse reactions, and abundant availability. Hence, research into and applications of olfactory stimulation in improving cognitive dysfunction have raised widespread concerns. This article reviews the relationship between the olfactory pathway and cognitive brain regions, and explores the mechanism by which natural plant essential oils alleviate cognitive dysfunction through olfactory stimulation in order to provide a reference for improving cognitive function via olfactory stimulation.
  • Original articles
    LONG Renjie, WANG Baogang, SONG Yabin
    Military Medical Sciences. 2024, 48(9): 664-670. https://doi.org/10.7644/j.issn.1674-9960.2024.09.004
    Objective To optimize the solid-phase synthesis process of phosphorodiamidate morpholino oligonucleotide (PMO) and determine the optimal reaction conditions. Methods The PMO tetramer PMO-TTTT was synthesized according to the reported reaction conditions, followed by purification through a semi-preparative high-performance liquid chromatography (HPLC) process. PMO-TTTT was structurally verified using nuclear magnetic resonance (NMR) and high-resolution mass spectrometry. With purified PMO-TTTT as a reference, a calibration curve was established, which subsequently guided the optimization of the reaction conditions for the solid-phase coupling reaction process, including the organic base, additives, duration of reaction and temperature. Under the optimized reaction condition, the anti-influenza A virus PMO sequence, PMO-flu, was synthesized and purified using a nucleic acid purification device. Results The optimal parameters for PMO solid-phase synthesis were determined. The organic base was N-ethylmorpholine, the additive was lithium iodide, the best temperature was 30 ℃, and the duration was 90 minutes. Conclusion The PMO solid-phase synthesis process has been established. LiI has been screened as a potent coupling reaction additive which could significantly boosts the efficiency of PMO solid-phase synthesis.
  • Original articles
    ZHAO Wenbin, LUO Xiaowei, TONG Fan, ZHENG Xiangwen, ZHAO Dongsheng
    Military Medical Sciences. 2024, 48(7): 524-529. https://doi.org/10.7644/j.issn.1674-9960.2024.07.007
    Objective To analyze the hotspots and developments in the field of language model-assisted artificial intelligence (AI) for antibody design and optimization in order to provide reference for research on development of antibodies. Methods By using CiteSpace software, hotspots of research were analyzed based on literature retrieved from the Web of Science, PubMed, and Scopus databases, focusing on three pivotal areas of research related to antibody design and optimization: the construction of pre-trained language models for antibodies, the generation of antibody sequences, and the prediction of three-dimensional structures of antibodies. In addition, this analysis reviewed the major advances in each of the specified research tasks, focusing on the delineation of similarities and differences across studies and dominating challenges in this field. Results From 2019 (10 publications) to 2023 (89 publications), the scale of and interest in this field kept increasing. Hotspots involved leveraging language models to assist the design or optimization of humanized, high-affinity, and highly specific antibodies. Within each research, methods were characterized by the diversity of model architectures, consistency of training data, and variations in training strategies. Challenges to the field included sparse antigen data, computational power limitations, and insufficient integration of wet and dry lab experiments. Conclusion Research in language model-assisted AI antibody design and optimization is gaining momentum and proves fruitful. However, researchers should be alert to the inadequate attention to antigen-antibody interactions and insufficient integration of experimental and computational validation, conduct more in-depth research and expand applications.
  • Original articles
    HUANG Ping, ZHANG Guanying, CHI Xiangyang, SUN Hancong, FANG Ting, YU Changming, CHEN Wei
    Military Medical Sciences. 2024, 48(7): 501-508. https://doi.org/10.7644/j.issn.1674-9960.2024.07.004
    Objective To construct secretory IgA (sIgA) based on the previously screened IgG neutralizing antibody ZW2G10 against SARS-CoV-2, evaluate its activity and find out about the biodistribution of sIgA in ICR mice after nasal administration. Methods After expression, purification, and identification, sIgA was evaluated for its binding and neutralizing activity through ELISA and pseudovirus-based neutralization assays. SIgA was coupled with Alexa Fluor 750 dye and administered to mice via nasal administration. In vivo imaging was used to observe the biodistribution of sIgA. After dissection of the mice, the biodistribution of sIgA in various tissues and organs was observed. Results Compared with IgG, sIgA retained the binding ability to SARS-CoV-2 S proteins, and its neutralizing ability was enhanced. After nasal administration of a single dose of 1 mg/kg, sIgA could be retained in the lungs of mice for more than 72 hours. SIgA could be detected only in the nasal cavity and gastrointestinal tract within 8 h of administration, but not in the heart, liver, kidney, spleen, brain, bladder or blood. Conclusion In this study, a universal and efficient sIgA expression system has been established. sIgA can effectively target the respiratory tract and lungs after nasal administration. SIgA is expected to become a potential drug that provides immediate passive immune protection.
  • Original articles
    MENG Fanheng, LUO Fuyao, FENG Ting, YANG Yu, XU Rui, ZHU Shuaiming, SHAN Junjie
    Military Medical Sciences. 2024, 48(3): 202-212. https://doi.org/10.7644/j.issn.1674-9960.2024.03.007
    Objective To establish the characteristic chromatograms of thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) of the aqueous-extract of Inula japonica Thunb.,and to determine the contents of six components (chlorogenic acid,caffeic acid,isoquercitrin,1,5-dicaffeoylquinic acid,4,5-dicaffeoylquinic acid and inulicin) in the aqueous-extract. Methods (1)The HF254 TLC silica gel plate,developing solvents of n-butanol-acetone-pyridine-water-glacial acetic acid (1∶5∶3∶1∶10 μL) and 10% sulphuric acid-ethanol were used before the chromatographic spots were examined at 365 nm. (2)The Sino Chrom ODS-BP column (ϕ4.6 mm× 250 mm,5 μm) and a mobile phase of 0.05% phosphoric acid solution and acetonitrile were used. The flow rate was 0.8 mL/min,the column temperature 35℃ and detection wavelength 205 nm. (3)The analytic conditions of the six components were similar to those described in method (2),but the wavelengths were respectively 203 nm (inulicin),256 nm (isoquercitrin) and 327 nm (caffeic acid,chlorogenic acid,1,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid). Results (1)The TLC chromatograms showed fine properties before and after the colour developer was sprayed. (2)Twenty-eight common peaks were marked in the HPLC characteristic chromatogram,so were ten components (chlorogenic acid,caffeic acid,1,5-dicaffeoylquinic acid,4,5-dicaffeoylquinic acid,taxifolin, rutin, quercitrin, isoquercitrin, luteolin and inulicin). The aqueous-extracts of eleven batches of materials of Inula japonica shared much similarity based on similarity and cluster analysis. (3) There were good linear relationships,and the linear ranges of chlorogenic acid,caffeic acid,isoquercitrin,1,5-dicaffeoylquinic acid,4,5-dicaffeoylquinic acid and inulicin were 3.25-65.00 μg/mL,4.00-80.00 μg/mL,1.60-32.00 μg/mL,17.75-355.00 μg/mL,2.50-50.00 μg/mL and 3.75-75.00 μg/mL,respectively. The contents of chlorogenic acid,caffeic acid,isoquercitrin,1,5-dicaffeoylquinic acid,4,5-dicaffeoylquinic acid and inulicin in elven batches of water-extract from Inula japonica were 3.38-6.66 μg/mg,2.13-7.35 μg/mg,0.51-1.57 μg/mg,15.81-24.87 μg/mg,0.50-1.08 μg/mg and 0.77-4.73 μg/mg,respectively. Conclusion The specific TLC and HPLC characteristic chromatograms can help ensure accurate quantitative determination of six components of the water-extract of Inula japonica,which can be used for quality control of the water-extract of Inula japonica.
  • Reviews
    DING Yufan, WANG Yating, LIU Weili, SHEN Zhiqiang
    Military Medical Sciences. 2024, 48(9): 690-694. https://doi.org/10.7644/j.issn.1674-9960.2024.09.009
    A high-altitude environment is characterized by low oxygen levels, low pressure, and low temperatures. Exposure to the plateau environment often causes damage to the body, leading to the occurrence of acute mountain sickness/chronic mountain sickness(AMS/CMS). Research indicates that acute or chronic exposure to the special environment can result in overall organ dysfunctions, such as those in the heart and gastrointestinal tract. The damage to the body caused by exposure to the plateau environment is closely related to acute and chronic hypoxia. Physiological maladjustment or disease is usually accompanied by changes in the structure of the gut microbiota. There have been reports on the correlations between the gut microbiota and bodily harm caused by high-altitude exposure. However, the specific types of bacteria involved and the mechanisms of action are still under investigation. This article reviews the intestinal tissue damage caused by low oxygen levels, immune activation, changes in microbial community structure, and differential metabolic products. The association and underlying mechanisms between bodily harm due to high-altitude exposure and the intestinal microbiota are also explored in hopes of stimulating new lines of thought related to the prevention and treatment of bodily harm caused by exposure to the plateau environment.
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