未来海战中，反舰导弹将作为交战双方的主要作战武器。掌握反舰导弹打击舰船后的伤亡情况及伤员伤情分布对卫勤保障建设有着重要意义。本文通过历史数据收集及文献查阅，对二战以来的有关资料进行了整理分析。统计结果显示反舰导弹造成的伤亡比例增高，受打击舰船沉没的几率减小；在未来的医疗救治中，要着重关注炸伤、烧伤、吸入伤、贯通伤的救治，同时，也应警惕海水浸泡伤对伤员的危害。

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.;

Military training injuries are a common and frequently occurring disease in the army， which pose a serious risk to the health of soldiers and combat effectiveness. On the basis of the larger number of pilot projects for military training injury prevention and control and the "three tours" carried out by the whole army， the research group organized experts in related fields of military training injury prevention and control to compile the Expert Consensus on Principles of Diagnosis and Prevention of Military Training Injuries （hereinafter referred to as the "Consensus"） in line with the principles of putting prevention first， taking into account the reality， highlighting key points and proper rehabilitation by reference to the Regulations on Health Protection in Military Training. The "Consensus" has explicitly specified the definition， diagnostic basis， diagnostic criteria， classification criteria for injuries， diagnostic points， treatment principles and prevention principles of military training injuries. It aims to guide military surgeons at each level to effectively carry out early prevention， standardized diagnosis， treatment and rehabilitation intervention of military training injuries， which will play an important role in the prevention and treatment of military training injuries in the whole army.

Heat stress seriously affects body health and damages the morphology and function of cells, while heat acclimatization can effectively slow down this damage effect and induce cells to produce heat tolerance. The mechanism of heat acclimatization is very complicated, and its physiological effects are clear, but the regulatory mechanism may be brought into play by multiple regulatory pathways, with a variety of biological macromolecules involved in the regulation of body temperature and thermal endurance. Sofar, the potential mechanism of the protective effect of heat acclimatization on heat stress injury of cells has not been fully elucidated. In this paper, the research progress in the effect of cell heat stress injury and the mechanism of heat acclimatization against heat injury is reviewed.

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.

Sepsis is a global health issue that poses a serious threat to human health. The high incidence and complex pathogenic mechanism of sepsis are the main causes of death in critically ill patients. Cytokine storm is a phenomenon characterized by a tremendous amount of cytokine production,which is manifested as the uncontrolled systemic inflammatory response caused by the overactive immune system and plays an important role in sepsis. This article reviews the research progress in the mechanism and treatment of cytokine storm in sepsis in order to provide new ideas and strategies for clinical practice.

目的 从技术管理和情报研究角度评估经颅磁刺激技术的研究活跃度、技术成熟度以及发展现状，以期为该技术的研究与临床应用、技术评估实证研究提供参考和借鉴。方法 选取经颅磁刺激技术的文献和专利数据作为研究样本，综合采用统计分析、社会网络分析等方法，运用Bicomb、Loglet Lab和UCINET软件，进行数据统计分析、网络图谱绘制等。结果 经颅磁刺激技术当前具有较高的研究活跃度，技术发展处于第2阶段由成长期向成熟期的过渡时期。技术的研究方向分散、深度不足，核心主题仍然缺乏。现阶段研究热点将为经颅磁刺激技术的临床应用提供支持。结论 在下一发展阶段，经颅磁刺激技术机理机制的解析、神经生物效应研究等主题有望成为研究热点。技术评估实证研究中，应加强多维度数据的挖掘与分析，引入专家咨询法。

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.;

There is growing evidence that the pathogenicity of Corynebacterium has been underestimated,and that this group of bacteria can even infect immunocompetent individuals without susceptible factors. Corynebacterium has come to be recognized as important opportunistic pathogenic bacteria. In recent years,there have been successive cases of genitourinary tract infections in males caused by C.glucuronolyticum that not only shows specificity for the genitourinary tract of males,but, as an opportunistic pathogenic bacterium,can cause male non-gonococcal urethritis,chronic bacterial prostatitis,persistent or recurrent cystitis without precipitating factors and other genitourinary tract infectious diseases. This paper reviews literature related to C.glucuronolyticum in terms of biological characteristics,epidemiological characteristics,possible pathogenic mechanisms,clinical significance and related antibacterial drug sensitivity of the bacteriumin order to provide data for the diagnosis and treatment of patients.

With the rapid development of aerospace in China, the influence of the space environment on astronauts has attracted more attention. Microgravity is extremely important for cognitive ability of the brain, which is closely related to the successful completion of the spaceflight mission. Therefore, the negative influence of microgravity on cognitive ability is an important issue to be solved urgently in space medicine. This review summarizes the effects of microgravity on cognition, possible mechanisms, and ways to reduce the negative effects of microgravity. It is hoped that this study will provide support for the aerospace development of China.

Objective To investigate the effects of nucleophosmin 1 （NPM1） on the proliferation and migration of cholangiocarcinoma cell lines Huh28 and RBE, and to explore the potential mechanism. Methods Recombined plasmid containing NPM1 was transiently transfected into Huh28 and RBE cells for overexpression of NPM1. Small interfering RNA （siRNA） was used to knock down the endogenous NPM1 in Huh28 and RBE cells. To verify the effects of overexpression and knockdown of NPM1, NPM1 protein expression levels were detected in Huh28 and RBE by Western blotting assays. CCK-8 assays were used to assess the proliferation of Huh28 and RBE cells. The effects of NPM1 on migration and invasion of Huh28 and RBE cells were verified by Transwell assays.Quantitative real time polymerase chain reaction （qPCR） and Western blotting assays were performed to detect the mRNA and protein expression levels of specific genes in epithelial-mesenchymal transition （EMT）, including cadherin 1（CDH1）, cadherin 2（CDH2）, β-catenin1（CTNNB1） and vimentin（VIM）. Log-rank test was used to reveal the difference in survival between cholangiocarcinoma patients with high and low NPM1 expressions. Results Knockdown of NPM1 reduced the proliferation, migration and invasion of Huh28 and RBE cells, whereas overexpression of NPM1 induced the proliferation, migration and invasion of Huh28 and RBE cells. Overexpression of NPM1 induced EMT, whereas knockdown of NPM1 reduced EMT. NPM1 was up-regulated in cholangiocarcinoma tissues compared with non-tumor liver tissues, and its high expression was marginally associated with poor prognosis in patients with cholangiocarcinoma. Conclusion NPM1 can promote the proliferation, migrationand invasion of cholangiocarcinoma cell lines by activating the EMT pathway. Thus, NPM1 might act as an oncogene in the development of cholangiocarcinoma.

Objective To analyze in vivo metabolites of isorhamnetin in mice after oral administration using ultra-high performance liquid chromatography coupled with quadrupole/time-of-flight tandem mass spectrometry （UPLC-Q/TOF-MS/MS）. Methods Twelve C57BL/6J mice （n=12） were randomly divided into the isorhamnetin group and the vehicle treatment group. Isorhamnetin was reconstituted in carboxymethyl cellulose sodium suspension （0.5%）, and administrated at 100 mg/ （kg·d） by oral administration. Meanwhile, the same amount of carboxymethyl cellulose sodium solution （0.5%） free of isorhamnetin was given to the vehicle group. The feces, urine, blood and bile of mice were collected and separated on different C18 columns with gradient 0.1% aqueous formic acid solution-acetonitrile as the mobile phase. The temperature of the column and the autosampler was set at 30°C and 4°C respectively. In the negative ESI mode, each sample was scanned from m/z 50 to 1700. Results After the administration of isorhamnetin, 1 parent compound and 25 metabolites were identified, which were respectively distributed in the feces （19）, urine （15）, blood （5） and bile （2） of mice. Conclusion Isorhamnetin can induce hydroxylation, dehydroxylation, glycosylation, deglycosylation, sulfation, methylation, acetylation, hydrogenation and glucuronidation in mice. The consequent metabolites may be the potentially effective compounds of isorhamnetin.

Proteolysis-targeting chimeras （PROTAC） is a bifunctional molecule that targets protein of interest （POI） for degradation by co-opting the ubiquitin-proteasome system （UPS）. In recent years, PROTAC technology has been widely explored as a novel therapeutic strategy for cancer, autoimmune diseases, neurodegenerative diseases and viral infection, which has become a hot spot and priority for drug development. This review is intended to outline the important milestones and the key research progress in the field of PROTAC, offer recommendations on the design of PROTAC,and describe the challenges to and prospects of targeted degradation by PROTAC.

Objective To establish a bimolecular fluorescence complementary technology based on a red fluorescent protein,yEmRFP, for detection of protein-protein interactions in yeast cells. Methods The N-terminal fragment （1-159 aa, RN159） and C-terminal fragment （160-236 aa, RC160） of yEmRFP were fused with bJun and bFos or bFosΔZip, respectively, to construct recombinant plasmids via molecular cloning technology. Among them, bJun and bFos were the basic leucine zipper domains （bZIP） of transcription factors Jun and Fos, and there was no interaction between bFosΔZip and bJun, which could be used as a negative control. After the recombinant plasmids were transformed into yeast cells, the transformed yeast colonies were screened in auxotrophic medium, and the fluorescence signals of recombinant yEmRFP protein in yeast were detected by fluorescence microscopy and flow cytometry. Thus, it was confirmed that this method was effective for investigating protein-protein interactions. Results The recombinant plasmids of RN159 and RC160 fused with bJun and bFos or bFosΔZip were constructed. The interactions between bJun and bFos reassembled yEmRFP into complete fluorescent protein in yeast cells and strong red fluorescence signals were detected by fluorescence microscopy.About 25% of the 20 000 yeast cells counted by the phycoerythrin （PE） channel of flow cytometry had red fluorescence signals. No fluorescence signal was detected in the negative control group,and no red fluorescentce signal was clearly detected in the same PE channel of the flow cytometry, thus indicating that this system had no self-activation. Conclusion In this study, a yEmRFP-based yeast bimolecular fluorescence complementation technology has been developed, which can be used for direct and rapid detection and screening of protein-protein interactions.

Objective To investigate the roles of autophagy and autophagy-related proteins ATG5/ATG7 in the expansion of neural stem cells （NSCs） in vitro. Methods NSCs were isolated from the brains of embryonic SD rats and cultured in vitro. During the expansion of NSCs in vitro, the changes in the diameter of neurospheres were observed, the cell viability was detected by CCK-8 kit, the protein expression levels of ATG5, ATG7, LC3 and PCNA were analyzed by Western blotting assay,the formation of autophagosomes was observed under a transmission electron microscope （TEM）, the expressions of LC3 and Ki67 were analyzed by immunofluorescence, and the cell proliferation ability was tested by EdU assay. The role of autophagy and ATG5/ATG7 in the expansion of NSCs was evaluated after Baf A1 treatment or knockdown of Atg5/Atg7 with siRNA. Results Autophagy and proliferation were gradually enhanced with the expansion of NSCs in vitro. The proliferation of NSCs was significantly inhibited after autophagy was blocked with Baf A1, indicating that the increase in autophagy could promote the proliferation of NSCs. In addition,compared with the control group, autophagy and proliferation of NSCs decreased significantly after knockdown of Atg5 or Atg7. Conclusion The expansion of NSCs in vitro can be promoted by autophagy,in which ATG5 and ATG7 are critical to autophagy of NSCs.

Objective To investigate the effect of coactosin-like protein 1（COTL1） knockdown in macrophage on inflammation responses and its possible molecular mechanism. Methods A lentiviral vector was constructed to specifically knockdown the expression of COTL1, and transfected into RAW264.7 cells, which were stimulated by lipopolysaccharide （LPS） to induce a cellular model of inflammation. The effect of COTL1 knockdown in RAW264.7 cells was detected by Western blotting and real-time quantitative polymerase chain reaction （qRT-PCR） in the levels of protein and mRNA. The phosphorylation levels of extracellular signal-regulated kinase （ERK）, c-Jun N-terminal kinase （JNK） and inhibitor of nuclear factor κB kinase （IKK） in RAW264.7 cells stimulated by LPS and the changes in phosphorylation levels of ERK, JNK and IKK in RAW264.7 cells with COTL1 knockdown stimulated by LPS were detected by Western blotting. LPS-induced nitric oxide （NO） production was measured by Nitric Oxide Assay Kit. The levels of TNF-α, IL-1β and IL-6 in supernatants of RAW264.7 cells with COTL1 knockdown stimulated by LPS were determined by enzyme-linked immunosorbent assay （ELISA）. Results Knockdown of COTL1 in RAW264.7 cells could resist the activation of JNK and NF-κB inflammatory signaling pathways caused by LPS, and alleviate the expressions of downstream inflammatory cytokines and reactive nitrogen, which in turn reduces the overall inflammation. Conclusion COTL1 knockdown in macrophages can mitigate the inflammatory response by reducing the activation of JNK and NF-κB signaling pathways, the secretion of downstream inflammatory cytokines and the production of NO.

This paper is intended to analyze the driving force behind and main strategies for innovation and development of individual protective equipment in extreme environments by the U.S. Armed Forces,and outline the current developments and representative achievements of individual protective equipment by the U.S. Armed Forces for environments of high altitude, extreme cold and extreme heat. It is recommended that the top-level design be adopted, physiological modeling and analysis technologies for big data be given more attention, key technologies be innovated, and intelligent, information-based and lightweight new individual medical protective equipment be developed with more effort.

血管生成是肿瘤生长、增殖和迁移必不可少的过程。肿瘤血管生成机制非常复杂，受到多种信号因子的调节。VEGFR作为影响血管生成的关键信号因子，在过去二十多年里成为了抗肿瘤药物研发的重要靶点。VEGFR已被证实是肾细胞癌、胃肠道间质瘤、肝细胞癌、白血病等多种类型肿瘤的治疗靶点。基于小分子药物与靶蛋白的构效关系能够使得新化合物结构的设计和优化更加高效，因此成为关注的重点。目前，已有14个VEGFR抑制剂上市，许多VEGFR抑制剂正处于临床试验阶段，还有大量的在研小分子化合物处于活性测试阶段。本文综述了已上市的14个VEGFR抑制剂及部分具有发展潜力的处于临床试验阶段和近期公开发表的VEGFR小分子抑制剂的研究进展，就其结构特征和临床适应症进行了总结，并阐述了未来VEGFR抑制剂的主要研究方向和面临的挑战。

Trauma is the main cause of death and disability on the battlefield, and traumatic hemorrhage is the main cause of potentially preventable death. As an alternative way of peripheral intravenous infusion, intraosseous infusion is increasingly used in battlefield trauma resuscitation, and playing a positive role. With the continuous updating of Tactical Combat Casualty Care （TCCC）, and the practice and research of combat injury treatment, ways to use intraosseous infusion in the resuscitation of battlefield trauma patients are becoming more specific. This paper summarizes the applications of intraosseous infusion in battlefield trauma resuscitation in order to provide reference for the application of this technology in the treatment of war injuries in China.

Objective To investigate the effect of undercarboxylatedosteocalcin（ucOCN） on erastin-induced ferroptosis in mouse hippocampal HT22 neurons. Methods HT22 hippocampal neurons were treated with erastin to induce a ferroptosis model. The cells were divided into the control group,ucOCN group,erastin group, and erastin+ucOCN group. CCK-8 analysis was used to detect the proliferation of cells in each group. The morphological changes of cells in different groups were observed under optical microscope, and the number of surviving and dead cells were detected by Live/Dead staining. Superoxide anion fluorescent probe （DHE） was used to detect the content of reactive oxygen species （ROS）, and TMRE probe was used to detect the mitochondrial membrane potential. Quantitative real-time polymerase chain reaction（qRT-PCR） was verified the interference efficiency of siRNA on OCN. The protein expression levels of ferroptosis-related proteins-glutathione peroxidase 4 （GPX4） and solute carrier family 7, member 11 （SLC7A11） were detected by Western blotting. Results Twenty-four hours of treatment of HT22 cells with 30 μmol/L erastin significantly inhibited cell viability, increased cell apoptosis, increased intracellular ROS content and decreased the mitochondrial membrane potential. Compared with the erastin group,the cell survival rate of erastin+ucOCN group was increased, the level of intracellular ROS was significantly reduced, and the mitochondrial membrane potential was restored. Western blotting results showed that ucOCN could promote the expressions of GPX4 and SLC7A11 proteins in ferroptosis cells. Conclusion ucOCN has an inhibitory effect on erastin-induced ferroptosis in HT22 cells.

In the future, all-domain operations will pose new challenges to Combat Casualty Care. To deal with these challenges, the U.S. military has continued to innovate the model and concept related to health services,impacting the new style of Combat Casualty Care. This article summarized the U.S. military's progress in Combat Casualty Care management and research in 2021, analyzed the measures taken by the U.S. military, including the continuous promotion of the health-information system reform, updating the new edition of Combat Casualty Care Guidelines, and organizing advanced training on Prolonged Casualty Care by focusing on the layout of a number of prospective projects as well as the new technologies and equipment for Combat Casualty Care in order to provide reference for the development of Combat Casualty Care here in China.

Patients with anti-melanoma differentiation-associated gene 5 （MDA5） antibody-positive dermatomyositis （DM） are more vulnerable to rapidly progressive interstitial lung disease （RPILD） and have a high mortality rate. Multiple prognostic factors have been identified, such as forced vital capacity （FVC）%, anti-MDA5 titer, serum ferritin, levels of Krebs Von den Lungen-6（KL-6）, and percentage of CD4⁺CXCR4⁺ T cells. These parameters are used for prediction of the severity of ILD, response to treatments and potential survival. Currently, the choice of therapies for patients with anti-MDA5 antibody-positive DM and RPILD is largely empirical, including "triple therapy" （high-dose glucocorticoids combined with tacrolimus and intravenous cyclophosphamide） and the use of Janus kinase （JAK） inhibitors. These therapies are based on published literature. However, better treatment options are urgently needed for DM patients with positive anti-MDA5 antibody and ILD, especially for advanced patients. In this article, the etiology, pathogenesis, clinical features, treatments, prognosis, and factors affecting prognosis of DM with positive anti-MDA5 antibody and ILD are reviewed.

The term “junshi yixue” has two meanings in Chinese. One is health care among the military troops and the other is military medical sciences. Another term “weisheng qinwu” also has two meanings in Chinese. One is the administration of military health care and the other is military medical services. Different meanings of these terms have left the Chinese military healthcare providers confused for many years. This article discusses in detail the different meanings of those two terms and draws three conclusions about their relationships.

Synthetic biology not only has broad economic prospects and social benefits, but also has potential application value in the military field. In recent years, the U.S. Armed Forces has grasped the frontier hotspots of synthetic biology, carried out applied research of synthetic biology in the military field, and sought innovative breakthroughs in the fields of military materials, military energy, military medicine and military sensing. This paper analyzes the development of synthetic biology, the prospect of military application and the deployment of related science and technology of the U.S. Armed Forces for reference.

Ataxia-telangiectasia mutated （ATM） is a protein encoded by ATM gene. ATM as an important factor regulating oxidative stress response can maintain redox homeostasis in vivo. This review discusses the mechanism of ATM activation by oxidative stress,the role of ATM activation in alteration of cell redox homeostasis,cell metabolism and autophagy,and its relationship with diseases. It provides a new idea for future study on the biological function of ATM and its application to the treatment of related diseases.

Objective To identify the sensitive indexes for heat acclimatization by observing the changes of physiological and psychological indexes in the process of heat acclimatization training in order to recommend workable on-the-scene expertise. Methods One hundred and thirteen young male soldiers were enrolled for fourteen days of heat acclimatization training. 3000-meter running was chosen as the quantitative load exercise. The changes of physiological and psychological indexes before and after 3000-meter running at four time points in the process of thermal conditioning training were monitored. Such devices as the body activity meter with a heart rate belt, infrared thermometer and weight scale were used to monitor the heart rate during the plateau phase, body temperature （temperatures of the ear, forehead and palm skin）, amounts of perspiration during the 3000-meter running and the time taken by the 3000-meter running. Rating of perceived exertion（RPE）, thermal sensation（TSV） and sweat feeling index（SFI） were measured by means of questionnaires. Results With the prolongation of heat acclimatization training, the D-value of ear temperatures before and after 3000-meter running trended up （P<0.05） before trending down. The 3000-meter running was finished in a shorter time （P<0.01）, that is, the soldiers were improved athletically. The training-impulse（TRIMP） of 3000-meter running （heart rate × performance） was significantly decreased （P<0.01）, suggesting enhanced cardiovascular function. Conclusion The TRIMP of 3000-meter running and D-value of ear temperatures are easy to monitor and sensitive to changes, which can be used as the first-choice indexes for the evaluation of heat acclimatization at the site of training.

Objective To analyze the potential active ingredients, targets and mechanism of anti-influenza effect of Moslae Herba using network pharmacology methods. Methods The chemical composition of Moslae Herba was retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP）. The potential targets of compounds were collected from the SwissTargetPrediction database, and the influenza targets were retrieved by GeneCards, OMIM database and literature mining. The ingredients-targets′ network was constructed with Cytoscape, and the protein-protein interactions （PPIs） of intersection targets were obtained from the STRING database and imported into Cytoscape. The intersection targets′ enrichment analysis of gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） was carried out by Metascape. Results Fourteen active ingredients and 243 potential targets of Moslae Herba were found and 1088 influenza-related targets were obtained. There were 45 targets where the components of the Moslae Herba and influenza intersected. There were 14 effective active compounds of Moslae Herba that were effective influenza, among which the six key ingredients were chryseriol, luteolin, kaempferol, kumatakenin, acacetin and quercetin. PPI network analysis resulted in nine critical target proteins,including Akt1, SRC, HSP90AA1 and EGFR. Metascape gene enrichment analysis resulted in 708 GO terms, which were related to multiple biological processes such as cytokines, immunomodulation and oxidative stress. One hundred and thirty KEGG pathways were also obtained through gene enrichment analysis, involving pathogen infection, PI3K-Akt signaling pathway, chemokine signaling pathway and phospholipase D signaling pathway. Conclusion This study reveals that Moslae Herba may help treat influenza via its anti-inflammatory, antiviral and immunomodulatory proporties, which provides valuable reference for future experimental studies.

Objective To study the mechanism by which liposomal sildenafil （LS） protects against zinc chloride （ZnCl₂） smoke inhalation-induced acute lung injury （SI-ALI）. Methods LS was prepared with the ammonium sulfate gradient method. Saline, LS, and budesonide were intratracheally administered into the lungs of mice to establish a model, LS, and budesonide groups, respectively. The mice were subjected to three minutes of inhalation of ZnCl₂ smoke. Forty-eight hours later, the mechanisms by which LS helped protect against such injuries were explored using behavioral tests, tissue sections, lung wet/dry weight ratios, immunohistochemical analysis of interferon-γ and nuclear factor-κB, and the expressions of tumor necrosis factor-α, interleukin-1β, superoxide dismutase, and malondialdehyde. Results LS could protect against SI-ALI more effectively than budesonide. Pulmonary delivery of LS reduced the SI-ALI of mice by maintaining their ability for physical activity, down-regulating the expressions of tumor necrosis factor-α, interleukin-1β, malondialdehyde, and nuclear factor-κB, and up-regulating the expressions of superoxide dismutase and interferon-γ. Conclusion Inhaled LS is a promising strategy for the prevention of ZnCl₂ SI-ALI by reducing inflammation and oxidative stress.

Objective To investigate the osteogenic differentiation capacity of adipose derived-stem cells （ADSCs） in mice with type 1 diabetes mellitus （T1DM）. Methods Ten C57BL/6 mice were randomly divided into two groups. Streptozotocin （STZ） was administrated to C57BL/6 mice through peritoneal injection to induce a T1DM model （n=5）, while the normal control group （NC group, n=5） was given the same volume of sodium citrate buffer injection. After one week, the random blood glucose of the mice was monitored and measured for 3 consecutive days. ADSCs were isolated and cultured from groin and gonad fat in two groups. Cell characteristics were identified by cell morphology, immunophenotype, and induced differentiation assay. The key transcription factors in adipogenic and osteogenic differentiation were measured by real-time quantitative PCR （qPCR） and Western blotting. To study the difference in the osteogenic differentiation ability between the two groups, the third passage ADSCs （P3） in the two groups were used for osteogenic differentiation assay in vitro. Alkaline phosphatase （ALP） staining was performed to measure the osteogenic capacity at 3, 5 and 7 d, respectively, and the expression of osteogenic differentiation related genes were detected by qPCR. Results In the T1DM group,the random blood glucose of the mice was found to be ≥16.7 mmol/L for 3 consecutive days. Typical symptoms of diabetes,including polydipsia,polyphagia,polyuria and slowed weight growth occurred in T1DM mice induced by STZ. Cultured cells from murine adipose tissue in the T1DM group and NC group were spindle-shaped and showed adherent vortex growth. Flow cytometry results showed that CD29 and CD90 were highly expressed, but the expressions of CD11b, CD34, CD45 and MHC-Ⅱ were lower or not expressed. Moreover, these cells presented adipogenic and osteogenic differentiation ability. These results demonstrated that ADSCs from T1DM mice and normal mice had been isolated. In vitro osteogenic differentiation assay results showed that the ALP activities in T1DM-ADSCs were decreased at 3, 5 and 7 d, compared with NC-ADSCs. Furthermore, the mRNA expression levels of RUNX2, OCN, ALP and BMP2 in T1DM-ADSCs were significantly reduced. Western blotting results revealed that the RUNX2 expression was decreased, while CEBPα was increased in T1DM-ADSCs. Conclusion ADSCs isolated from T1DM mice display weak osteogenic differentiation ability.

Objective To analyze the status quo and developments of British BMJ Military Health since 2011 using knowledge maps and other tools so as to help related health care institutions in China to keep track of British military medicine. Methods The Web of Science Core Collection was searched for articles from BMJ Military Health published between 2011 and 2022,and a total of 1475 pieces of literature were retrieved. Such knowledge map analysis tools as Hiscite,VOSviewer and CiteSpace were used for the research. Results The cited frequency of BMJ Military Health journals continued to trend up year by year,indicating that British military medicine received more attention. Royal Defense Medical Center,Birmingham University,University of London,Imperial College London and King′s College London were the leading contributors. The priorities of research involved the treatment of war wounds,maintenance of mental health,and the prevention and control of infectious diseases. Conclusion Constructing the knowledge maps of BMJ Military Health can help researchers gain insights into the developments of the journal.

The intestine-on-a-chip is a cutting-edge and in vitro research model of human intestines that has gained much attention in recent years. In comparison to traditional static culture models of intestinal epithelial cells, the intestine-on-a-chip offers numerous advantages. It accurately mimics the morphological structure of the intestine in vivo, allowing for the simulation of the microphysiological environment in intestinal tissues. Furthermore, it can be customized on a large scale and enables high-throughput drug screening. The intestine-on-a-chip has widespread applications in various areas, including the development of intestinal disease models, as well as drug screening and testing. The technology behind the intestine-on-a-chip is based on a co-culture system of intestinal epithelial cells and other cell types. Such chips can not only construct three-dimensional structures such as intestinal microvilli and folds in combination with microengineering techniques, but also replicate the intricacies of the intestine. Microfluidic devices are employed to simulate biomechanical parameters like blood flow and physiological peristalsis within the intestinal tissues, thus giving such chips microphysiological characteristics akin to those of natural intestinal tissues and subjecting it to biomechanical regulation. This review provided an overview of the advances in intestine-on-a-chip technology, focusing on cell co-culture techniques, microfluidic technology, and microengineering techniques. Furthermore, the application of this technology in intestinal disease modeling, and drug screening and testing were summarized.

Objective To construct a eukaryotic expression vector for adenosine triphosphate binding cassette subfamily G member 2（ABCG2） gene labelled with Myc tag and to study its biological function. Methods Using the human ovarian library as the template, human ABCG2 gene was amplified by PCR and inserted into the pXJ-40-myc expression vector.The recombinant plasmid pXJ-40-myc-ABCG2 was identified via enzyme digestion and sequencing before being transfected into the breast cancer cell line ZR75-1. The expression of ABCG2 protein was verified by Western blotting. Immunofluorescence was used to detect the localization of ABCG2 protein in cells. CCK-8 assay and wound-healing assay were used to determine the effect of ABCG2 gene on the proliferation and migration ability of breast cancer cells. The effect of ABCG2 gene on drug efflux of chemotherapeutic drug mitoxantrone was examined via the flow cytometric technique. Results The ABCG2 gene of about 2000 bp was retrieved from a human ovarian library and constructed on the pXJ-40-myc vector, and the sequencing results were consistent with the target sequences. Plasmids were extracted and transfected into human ZR75-1 breast cancer cells. The results of immunofluorescence showed that ABCG2 protein was mainly expressed in the membrane and cytoplasm of ZR75-1 cells. CCK-8 detection and wound-healing assay result showed that breast cancer cells transfected with pXJ-40-myc-ABCG2 had increased proliferation and migration ability compared with cells transfected with the empty vector. Flow cytometric analysis suggested that ABCG2 induced to increase drug efflux to mitoxantrone in cells. Conclusion A eukaryotic expression vector of pXJ-40-myc-ABCG2 is constructed, and the localization and drug resistance mediated by ABCG2 in cells are verified, which can help explore the role of ABCG2 in the development of breast cancer cells in the future.

The United States Bipartisan Biodefense Committee has issued the “ The Apollo Program for Biodefense-Winning the Race Against Biological Threats ” and the “ Athena Agenda： Advancing the Apollo Program for Biodefense”. This program conducted an exhaustive analysis of the scenario of biosecurity facing humans, proposed the objectives to be achieved, listed the priorities of research on core technologies and recommended specific measures for implementation. The program is an important tool for understanding the long-term U.S. response to biological threats. This paper outlines and analyzes the main contents of the program so as to provide reference for the construction of biosecurity defense in China.

The recording and analysis of activities of calcium signals in neurons is of critical importance in the field of neuroscience. Over the past three decades, various fluorescent calcium imaging techniques not only have been used in the imaging study of functional activities of neuronal communities, but also can be combined with specific markers to record the functional activities of specific types of neuronal communities. To analyze neural activities at the cellular level, a series of preprocessing such as motion correction, cell body recognition, calcium signal extraction and peak deconvolution is required for the collected video. However, current methods for manual preprocessing are time-consuming and laborious, so computer automatic analysis technology is urgently needed to quickly repair the jitter in the video, identify the position and outline of a single cell, extract its activity trajectory and infer the action potential peak. In this paper, the methods of calcium imaging data processing used in recent years are summarized, and the future developments are predicted.

When the body is exposed to a cold environment, it will induce the initial contraction of the peripheral blood vessels mediated by the sympathetic nerves, in order to preserve the heat resulting in a decrease in peripheral blood flow and lowering the skin temperature. But what is interesting is that usually 5-10 minutes after cold exposure, the surrounding skin blood flow and temperature will increase, which is known as induced vasodilatation response （CIVD）. CIVD is considered to be an important protective mechanism to prevent local cold injury. So far, it has been studied for nearly a century, but due to differences in research methods, the integration of CIVD literature into a coherent overall framework has been slow. During measurement of CIVD, the lack of standardization for the water temperature, location, depth, time, environmental temperature and individual factors of hand immersion make differences to the research conclusions of CIVD, which makes difficult the determination of the CIVD mechanism. This article summarizes the causes of CIVD and the methodology in research in order to quantify the parameters and influencing factors of CIVD, and reduce variability between and within subjects, improve the repeatability of CIVD, and provide reference for further research on CIVD.

Biological toxins are toxic molecules produced by specific microorganisms, plants or animals. Due to their wide range of sources and high toxicity, the availability of protein and non-protein toxins is becoming increasingly important, some of which are used for military purposes and developed as biotoxin warfare agents. In this paper, the classification and mechanism of action of biological toxins are discussed. In addition, the strategies for prevention and control of biological toxins as well as their therapeutic applications are reviewed.

Objective To investigate the effect of classical neurotransmitter-serotonin-on innate immunity against DNA viruses and its potential molecular mechanism. Methods Blood samples of mice were collected at different time points after HSV-1 infection. Serotonin concentrations in serum were detected by enzyme-linked immunosorbent assay （ELISA）. At the cellular level, cells were pretreated with serotonin or a serotonin transporter inhibitor before being stimulated by HSV-1 or exogenous dsDNA to induce type Ⅰ interferon production. The mRNA levels of type Ⅰ interferon and viral replication were detected by real-time quantitative PCR, and the activation of cGAS-STING pathway was detected by Western blotting. Mice were pretreated with serotonin and then infected with HSV-1. Serum was collected and the levels of type Ⅰ interferon were detected by ELISA. Organs were collected to detect the amount of virus replication by real-time quantitative PCR. Results After HSV-1 infection, serotonin concentrations in serum of mice increased. Pretreatment with serotonin inhibited the production of type I interferon in immune cells during HSV-1 infection, and the viral replication increased. In mice, serotonin treatment suppressed the host type Ⅰ interferon response during HSV-1 infection, resulting in elevated viral infection. Studies on the mechanism showed that the effect of serotonin depended on serotonin transporters. Serotonin could inhibit both the phosphorylation of key proteins in the cGAS-STING pathway and the expression of the interferon, thus affecting the host antiviral innate immunity. Conclusion Serotonin can inhibit antiviral innate immunity mediated by cGAS-STING pathway, which is expected to provide a new target for research and development of antiviral drugs.

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.

Given the profound influence of cognitive ability of military pilots on the skills of information acquisition, situational awareness and decision making in battlefield environments, cognitive enhancement targeting military pilots has become a hot topic in cognitive neuroscience. This paper elaborates the principles and effects of three intervention methods for cognitive enhancement of military pilots： cognitive training intervention, non-invasive brain stimulation technology, and cognitive enhancement drugs and supplements. Furthermore, prospective interventions will involve by big data modeling, artificial intelligence, and biomedical engineering so that cognitive enhancement research can become multi-modal, adaptive, and personalized. In the increasingly complicated and competitive battlefield environments, the progress in cross-disciplinary research on cognitive enhancement should be accelerated, which will help military pilots gain a competitive/edge on the battlefield in the future.

Objective To establish a method to identify novel adductive groups and their substrates upon exposure to OP. Methods Tandem mass spectrometry analysis and open search tools were employed to reveal the adducts of OP in human serum albumin （HSA）. Results Based on tandem mass spectrometry analysis, a new method was developed to study the structure and sites of novel adducts formed due to the exposure to OP, which could identify cysteine （C） as the new addition site of OP and their hydrolysis products using the open search strategy. A mass shift of 127.1370 that corresponded to a diagnostic ion in the MS-MS of m/z=128.1439 was observed. Conclusion This study has established a general strategy for identifying the structures and addition sites of novel OP-HSA adducts, which may be used to advance our understanding of the molecular processes behind acute and long-term harmful effects of OP.