This article reviews the research progress in military operational medicine of the U.S. Armed Forces in 2023 in terms of improved capabilities of health care in extreme natural environments, intervention strategies to improve nutrition and water security, assessment and monitoring of sleep quality, beeter hearing protection and optimization of physical fitness training. These measures are intended to improve the all-round and multifaceted level of operational performance of soldiers. This article is expected to provide useful reference for related research.

The important role of liquid-liquid phase separation in a series of biological processes, including regulation of gene transcription and translation, stress response, autophagy and the establishment of synaptic structure, has been widely accepted. Abnormal phase separation is associated with many human diseases, including neurodevelopmental disorders and neurodegenerative diseases. Studies have shown that some proteins associated with epigenetic modifications are also subject to liquid-liquid phase separation, suggesting that epigenetic modifications regulate the development and disease of the nervous system by regulating phase separation. This review summarized the important roles of epigenetic modification and phase separation in neurodevelopment and neurodiseases, and focused on the important roles of proteins related to epigenetic modification with phase separation characteristics. Understanding the correlation between epigenetic modification and phase separation will help fully understand the underlying mechanisms of neurodevelopment and neurodiseases, and will further provide new targets and strategies for the treatment of related diseases.

Human herpes simplex virus type 1 （HSV-1） infection of the upper respiratory tract is a common, mostly self-limiting disease. Reactivation of HSV-1 can sometimes cause lower respiratory tract infections. Coinfection of HSV-1 and other pathogens in the respiratory tract may cause severe diseases, resulting in HSV pneumonia and acute respiratory distress syndrome. This article reviews the symptoms and pathogenesis of HSV-1 infection or co-infections with other pathogens in the respiratory tract, as well as recent advances on drugs and vaccines for HSV-1.

The accumulation of fatigue during military operations may lead to decreased operational efficiency and non-combat attrition, which can impact combat effectiveness.On-site monitoring and evaluation of fatigue during military operations,as an important means to keep track of military operations and bring about quick changes in training, underlie the combat effectiveness of military personnel. Focusing on the on-site monitoring and evaluation methods of fatigue during military operations, this paper reviews the determinants of such fatigue as well as on-site monitoring and comprehensive evaluation methods so as to provide reference for accurate and efficient evaluation of fatigue during military operations and for early warning of such fatigue.

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.

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 PIKfyve^flox/flox mice. PIKfyve^flox/flox mice were cross-bred with UBC-Cre/ER^T2 mice to obtain PIKfyve^+/flox, UBC-Cre/ER^T2 mice and PIKfyve^flox/flox, UBC-Cre/ER^T2 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 PIKfyve^flox/flox,MX1-Cre mice to confirm the aforementioned results in a distinct mouse model. Results Successful generation of PIKfyve^flox/flox, UBC-Cre/ER^T2 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 PIKfyve^flox/flox,MX1-Cre mice were consistent with those of PIKfyve^flox/flox, UBC-Cre/ER^T2 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.

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.

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.

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.

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.;

Objective To design a search and rescue UAV that is portable and user-friendly in order to meet the needs of rescue personnel on the battlefield. Methods Three-dimensional design software CATIA was used to complete the structural design of the UAV body. In order to make full use of the internal space of the UAV body, folding wings were adopted to reduce the volume of the UAV.By using ABAQUS, the finite elements of the key parts of the UAV were analyzed before the modal analysis of the whole vehicle was conducted to verify the reliability of the structure. The robot simulation software Webots was used for motion simulation of the UAV. Results Simulation analysis and test verification suggested that the structural design of the UAV was well-grounded. It could be quickly and properly deployed by means of hand launch or barrels, which made it easier for rescuers to use the UAV. Conclusion The design and simulation research of UAVs with portable folding wings for search and rescue is of great significance for the research and development of physical prototypes. This study is expected to stimulate new ideas for the development of rescue equipment in the PLA, and contribute to miniaturization of UAVs.

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.

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.

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.

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.

Objective To establish an inhalation infection pneumonia model of C57BL/6J mice with highly virulent and multi-drug resistant Pseudomonas aeruginosa （PA） strain F291007, and to study the microbiological, pathological and immunological characteristics of this model. Methods The strain F291007 was isolated and identified before the bacterial suspension was administered to the mice via aerosolized intratracheal inoculation to establish the pneumonia infection model. In the course of infection, the conditions and survival of the mice were observed, and the bacterial loads, the histopathological states and the cytokine expression levels in the major organs were detected. Finally, three key cytokines were blocked to observe the survival of mice. Results The strain F291007 was isolated and identified. After lethal dose infection, all the mice died within 24 h. After sub-lethal dose infection, a large number of immune cells in the body were capable of phagocytosis and killing of invading pathogens, which was manifested as rapid clearance of bacteria in lungs and the exponential decrease of bacterial load with the passage of time. The pathological changes in lungs were most severe at 1 to 3 days but gradually recovered. After infection, interleukin-6 （IL-6）, IL-17A and tumor necrosis factor-α（TNF-α） in alveolar lavage fluid and serum were significantly increased at 1 to 3 days. After blocking of these three cytokines with specific antibodies, the survival rates of infected mice decreased significantly. Conclusion A mouse model of gradually-recovered pneumonia infection caused by PA inhalation has been established, suggesting that the first one to three days are critical to immune response after infection through multiple indicators. This mouse model can be used for research on the pathogenesis, immunoregulation and treatment evaluation of highly virulent and multi-drug resistant PA inhalation pneumonia infection.

Objective To explore the characteristics and mechanism of phase separation between TAR DNA binding protein-43（TDP-43） and ubiquitin. Methods The TARDBP gene and its truncated genes were inserted into vectors to construct recombinant plasmids for expression and protein purification. The phase separation system of ubiquitin and TDP-43 was constructed in vitro. The characteristics of the droplets formed via liquid-liquid phase separation were observed by fluorescence microscopy. The plasmids of ubiquitin and TDP-43 were co-transfected into HEK293T cells to observe aggregates containing TDP-43 and ubiquitin and find out whether TDP-43 could be ubiquitinated. Results The GFP-8Ub,TDP-43 full-length （FL） and truncated proteins were purified. TDP-43 FL and C-terminal domain（CTD） proteins were able to form droplets via phase separation with ubiquitin. The droplets changed into solid-like aggregates after prolonged incubation. Insolvable aggregates containing TDP-43 and ubiquitin were formed. TDP-43 was ubiquitinated under stress conditions in HEK293T cells after being co-transfected with ubiquitin and TDP-43 recombinant plasmids. Conclusion TDP-43 undergoes co-phase separation with ubiquitin,mainly driven by the multivalent interaction between TDP-43′s CTD structural domain and ubiquitin. The droplets finally form aggregates with solid-like properties. Under stress conditions,especially when the protein homeostasis is disrupted,TDP-43 and ubiquitin form aggregates while TDP-43 is ubiquitinated. This study reveals the basic mechanism of TDP-43 co-phase separation with ubiquitin and liquid-solid transformation.

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.

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.

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.

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.

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.

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.

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.

Objective To establish an auxiliary method for diagnosis of mild traumatic brain injury based on serum GFAP rapid detection test strips using immunochromatographic technology labeled with quantum dot microspheres. Methods The quantum dot microspheres were coupled with GFAP antibodies.The detection conditions were optimized to obtain the fluorescence probe in order to prepare the immunochromatographic test strips. An auxiliary diagnostic method was established after optimization of detection conditions. Finally, the auxiliary diagnostic effect of the test strips was evaluated using clinical samples. Results The serum concentration of GFAP could be detected by the optimized test strips within 13 mins with a detection limit of 0.15 ng/mL, and no more than 70 μL of the serum sample was required. In addition, good reproducibility was achieved by different batches of test strips （CV=10.7%）. The detection sensitivity and specificity of the strips to mild traumatic brain injury using 51 clinical samples were 95.24% and 96.67% respectively, indicating good effects of detection. Conclusion The developed test strips are user-friendly with reliable results, which can facilitate field rapid diagnosis of mild traumatic brain injury in complicated wartime environments.

Fatigue-related traffic accidents and fatalities have been extensively studied by scholars globally. Specialized vehicles, due to their unique mission profiles, are more likely to cause driving-related fatigue and serious consequences. This paper reviews the current research of fatigue driving by using an inductive analysis method to summarize the mechanisms, risk factors, and monitoring methods. This paper also offers a vision of priorities and methodologies for research in the future. It is recommended that the mechanisms of driving fatigue be explored at the molecular biological level and that fatigue monitoring systems be made more feasible via the combined application of non-intrusive monitoring in order to reduce the toll on life and property taken by driving fatigue.

Objective To evaluate the characteristics of dose distribution of neuronal networks in vitro on microelectrode arrays（MEAs） under 2.6 GHz radiofrequency（RF） exposure. Methods The MEAs were coupled with a real-time RF exposure setup, and electromagnetic simulation software was used to calculate the RF dose absorbed in cultured neuronal networks. A fiber-optic temperature probe was used for experimental validation and monitoring of the cell temperature during RF exposure.The MEAs were used to record the electrical activity of neurons. Results For an input power of 1 W,a specific absorption rate （SAR）level of （15.51± 2.48） W/kg was calculated, and the variability of the SAR distribution was 16%. In our experimental system, the temperature elevation of neurons was up to 0.15 ℃ for an SAR of 4 W/kg RF exposure. Conclusion The exposure device can provide high SAR efficiency and uniformity in the 2.6 GHz band, which is suitable for studying the real-time effects of RF fields on the electrical activity of neuronal networks in the 5G network band.

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.

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.

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.

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.

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.

Objective To observe the therapeutic effect of a self-formulated formula for psoriasis on imiquimod induced BALB/c mouse psoriasis model and explore its mechanism of action. Methods The BALB/c mice were randomly divided into the normal group,model group,and oral external group（all n=10）. The BALB/c mouse psoriasis like model was induced by using back application of 5% imiquimod cream to verify the therapeutic effect of the self-formulated formula for psoriasis. Before induction with imiquimod cream,as well as on the 3rd,7th,10th,and 12th day after induction,the distribution and tortuous changes of blood vessels in the skin of mice were observed by using photoacoustic imaging technology to evaluate the effect of the formula on abnormal angiogenesis. The local pathological changes in the skin of experimental mice wasevaluated by using the Hematoxylin-Eosin staining. The enzyme linked immunosorbent assay was used to detect changes in the content of cytokines such as tumor necrosis factor （TNF-α）,interleukin-17 （IL-17）,and interleukin-6 （IL-6） in mouse skin tissue and serum. By using the flow cytometry,the levels of cytokines such as Treg,Th1,and Th17 in mouse spleen were investigated. Results Compared with the model group,the area and severity index score of psoriasis （PASI） in the oral external group was significantly decreased （P<0.01）,and the levels of TNF-α,IL-17,and IL-6 in the skin of the oral external group were significantly down regulated （P<0.01）. Compared with the model group,the proportion of Treg,Th17,and Th1 cells in the oral external group was significantly reduced （P<0.05）,and the pathological scores of skin tissue （Baker's method） in the oral external group were significantly reduced （P<0.05）. Conclusion Self-formulated formula for psoriasis has a good therapeutic effect on psoriasis and can suppress psoriasis skin lesions through immunosuppressive effects.

Objective To investigate the applicability of the renal resistive index（RRI） combined with pulmonary hypertension （PH） in predicting the mortality risk of patients with sepsis. Methods The clinical and ultrasonographic data of 115 sepsis patients was retrospectively analyzed who were admitted to the emergency ICU of Beijing Chaoyang Hospital between May 2021 and October 2022. These patients were categorized into the death and survival group based on their 28-day outcomes. The basic information, laboratory tests and bedside ultrasound parameters were compared between the two groups. Logistic regression analysis was used to identify independent factors associated with mortality in sepsis. Receiver operating characteristic （ROC） curves were used to assess the role of age, RRI, and PH in predicting sepsis mortality. Results Among these patients, 61 were in the death group and 54 in the survival group. There were statistically significant differences between the two groups in terms of age, oxygenation indexes, lactate levels, B-type natriuretic peptide （BNP）, cardiac troponin, RRI, right atrial transverse diameters, right ventricular basal diameters and PH （P<0.05）. Multivariate logistic analysis showed that age, RRI, and PH were independent factors for mortality in sepsis patients （OR=1.087, 1.091, 3.261, P<0.05）. The areas under the ROC curve for age, renal resistive indexes, and pulmonary hypertension were 0.798, 0.729, and 0.711, respectively. The area for combined prediction under the curve for mortality risk in sepsis patients was 0.856, with a sensitivity of 83.6% and a specificity of 81.5%. Conclusion Age≥74 years, RRI≥0.73, and pulmonary hypertension are significant risk factors for mortality in sepsis. RRI combined with PH can be used for early warning to predict the mortality risk in elderly sepsis patients.

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.

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.

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.

Objective To study the effect of apilimod on hematopoietic cells in mice under steady-state conditions. Methods 6-8-week-old male C57BL/6J mice were divided into the solvent control group （vehicle） and apilimod administration group, which were intraperitoneally injected with the vehicle and apilimod 0.2 mL/mouse, respectively. Before and after administration, peripheral blood cell counts, the absolute value of hematopoietic stem and progenitor cells from peripheral blood/spleen/bone marrow and the concentrations of such cytokines as IL-10 in serum were compared between the two groups. In the hematopoietic stem progenitor cell detection experiment, a plerixafor（AMD3100） group and water for injection （WFI） control group were set up, which were injected with AMD3100 at 5 mg/kg and WFI 0.2 mL/mouse, respectively. Results The peripheral blood cell count of mice changed significantly at 6-12 h after a single intraperitoneal injection of apilimod 40 mg/kg, but returned to the pre-administration level at 24 h post-treatment. At 9 h after apilimod injection, the number of platelets of mice treated with apilimod was 78.2% of the pre-administration number, and the red blood cell count did not change significantly, but was lower than that of the vehicle group （P<0.05）. Additionally, the absolute value of lymphocytes decreased while that of neutrophils and monocytes increased. The absolute value of neutrophils at 9 h increased 8.7 times after treatment, and was significantly higher than that of the vehicle group （P<0.05）. Apilimod 10-50 mg/kg increased neutrophils of mice in a dose-dependent manner at 9 h after a single intraperitoneal injection （R⊃2;=0.9556）. Nine hours after injection of apilimod 40 mg/kg, the numbers of mononucleated cells（MNCs）, immature hematopoietic cells （lin^-） and lin^- Sca-1^- c-kit⁺ cells（LK） in the peripheral blood and spleen of the apilimod group were significantly larger than those of the vehicle group （P<0.05）. The number of lin^- Sca-1⁺ c-kit⁺ cells（LSK） from spleens of apilimod-treated mice was significantly larger than that of vehicle treated mice （P<0.05）. There was no significant difference between apilimod and AMD3100 treated mice in LK or LSK from peripheral blood and spleens （P>0.05） or in the proportion and number of hematopoietic stem progenitor cells in femur bone marrow between the apilimod group and vehicle group （P>0.05）. Apilimod administration changed the concentration of cytokines in serum. At 9 h post administration, the concentration of interferon-12p70（IL-12p70） decreased while those of interferon-10（IL-10） and tumor necrosis factor-α（TNF-α） increased 14.6 and 5.9 times, respectively. Conclusion apilimod has a significant regulatory effect on the number of hematopoietic cells in mice under steady-state conditions. Single intraperitoneal injection of apilimod can significantly affect the absolute value of mature blood cells in the peripheral blood of mice. Moreover, apilimod can increase the value of hematopoietic progenitor cells in peripheral blood and spleens, but has no effect on the value and cell cycle distribution of hematopoietic stem and progenitor cells in bone marrow. Furthermore, a single injection of apilimod resulted in a decrease in IL-12p70 levels, while increasing the concentrations of IL-10 and TNF-α in the serum.

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.;