Objective To establish a simulated model that can optimize strategies for medical evacuation in case of mass casualties,and to study the guidelines for centralized scheduling of evacuation vehicles. Methods A simulated model was constructed based on theories about discrete event simulation and on processes of medical evacuation. Evacuation processes under different scheduling strategies were simulated and quantitatively evaluated in terms of efficiency of evacuation and utilization of resources.The impact of key parameters on the medical evacuation system was analyzed. Results When the critically wounded were given priority,the rate of immediate treatment for the wounded was the highest（87.44%）,and the median waiting time for the wounded was 23.70 min. In terms of utilization of resources,the strategy of prioritizing the critically wounded delivered the best result,with an average of 2.94 persons evacuated per vehicle and an overall rate of vehicle utilization was 50.93%. The daily number of the wounded and the number of evacuation vehicles made a big difference in the performance of the rescue system. Command and scheduling had to be dynamically optimizedas required so as to strike a balance between the efficiency of treatment and utilizationof resources. Conclusion This simulated model for medical evacuation in case of mass casualties,which is based on theories about discrete event simulation,is flexible enough toback up the simulation of strategy optimization.

α 2-Macroglobulin （A2M） is a high-abundance plasma protein with a molecular weight of 720× 10³, containing 1451 residues and 11 domains, and was isolated and identified for the first time in 1946. The capture and inhibitory effect on proteases is the classical biological function of A2M. However, A2M can also interact with membrane receptors, cytokines, and growth factors, and act as a molecular chaperone to affect extracellular protein homeostasis so that it is involved in a wide range of physiological and pathological processes such as immunity, inflammation, and degeneration. This article reviews the structural characteristics of A2M, the reported molecular targets, the mechanism of action, and its biological effects in the hope of providing a new line of thought for the functional exploration and clinical applications of A2M.

Objective To identify potential drug target genes associated with idiopathic pulmonary fibrosis （IPF） and predict therapeutic candidates using a two-sample Mendelian randomization （MR） approach across the druggable genome. Methods Druggable genome data from the DGIdb database and Finan were integrated to identify overlapping genes. A two-sample MR analysis was performed to infer causal relationships between genes and IPF. Functional enrichment analyses,including Gene Ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG）,were conducted to explore biological pathways. Drug-target interactions were predicted via DSigDB database screening,followed by molecular docking simulations to evaluate binding affinities. Results Among the 2588 overlapping druggable genes,thirty exhibited significant causal associations with IPF （P< 0.05）. Four hub genes （NOD2,LATS2,LTA,and TCF7L2） were enriched in IPF-related pathways,notably Hippo and TNF signaling. Six potential therapeutics were identified： oxyphenbutazone,moexipril,α-galactosylceramide,GSK429286A,CGP74514A,and JW-7-24-1. Molecular docking confirmed strong binding affinities between these drugs and their targets. Conclusion This study has identified thirty druggable gene targets and six candidate drugs for IPF. The enrichment of hub genes in key pathways and validated drug-target interactions provide insights into IPF therapies.;

High intensity ultraviolet radiation exists in special military operation environments such as oceans, plateaus, polar regions and deserts, which is a leading contributor to eye damage and can lead to luminous keratitis, dry eyes, pterygium, cataract and macular degeneration. Ultraviolet radiation can cause acute and chronic injury to eyes by inducing DNA damage, oxidative stress and inflammatory reaction. The commonly used clinical drugs have played a role in relieving symptoms and promoting the repair of ocular tissues, but there are still limitations. The research on targeted therapeutic drugs, proteins and their derived peptides, vitamins and their coenzymes, as well as natural active ingredients of animals and plants has provided new ideas for the development of more effective drugs that can protect eyes from ultraviolet and for medical support to China’s army in special environments. Based on the literature currently available, this paper reviews the eye injury caused by ultraviolet radiation and therapeutic drugs in terms of types of eye diseases, injury mechanisms, treatment strategies and drug development.

In the Ukraine crisis since 2022, the Russian army has adopted a wide range of strategies for medical support as required by the battlefield, including adjusting the ways of medical evacuation, increasing the number of medical institutions and personnel, optimizing the mechanism for medical supplies, improving rehabilitation and sanatorium facilities, enhancing military medical education and training, developing new health care equipment and field rescue techniques. This paper analyzes the characteristics and effects of these new strategies implemented by the Russian army.

Objective To efficiently produce Clostridium perfringens alpha toxin （CPA） by using a prokaryotic expression system and systematically analyze its biological activity. Methods The CPA gene fragment fused with His-Tag sequence was cloned into a prokaryotic expression vector pTIG-Trx and transformed into E. coli TransB （DE3）. The IPTG was used to induce the expression of the target protein,and the protein was obtained by using Ni-column affinity purification. The cytotoxic effect of recombinant CPA protein on 293T,LS174T and SW480 cells,hemolytic effect on human and mouse red blood cells,and lethal effect on mice were further evaluated. Results The recombinant CPA protein with a relative molecular weight of about 45×103 and a purity of more than 90% was successfully obtained. It had significant toxicity to 293T,LS174T and SW480 cells and induced hemolytic reactions in human and mouse red blood cells at specific concentrations. Low dose of CPA protein could cause rapid death in mice in a short time. Conclusion This study successfully obtained the high purity CPA protein with good biological activity in vitro and in vivo,which laid a foundation for further study of the pathogenic mechanism of CPA and its potential application.

With the growing complexity and higher risk of modern warfare, artificial intelligence （AI） technologies have been increasingly used in the field of military medicine. This study investigates the innovative applications of AI in military medicine, focusing on practices in such countries as the United States, Israel and the United Kingdom. The research reveals that AI technologies have been extensively applied in battlefield medical training, casualty status monitoring, medical decision support and unmanned rescue operations. Through virtual reality simulation, intelligent decision support and vital sign monitoring technologies, AI has significantly improved the efficiency and precision of battlefield medical care. Despite challenges related to technological implementation, environmental adaptability and ethical controversies, future battlefield medical care will increasingly rely on unmanned systems and intelligent equipment to deliver efficient medical treatment through human-machine collaboration.

Transient receptor potential vanilloid 1 （TRPV1） ion channel, a non-selective cation channel, not only plays a key role in pain transmission but also serves as a bridge between the nervous system and immune system by regulating neuropeptide release, immune cell activation, and inflammatory signaling pathways. This article summarized its crucial role in inflammatory signal transduction, discussed the interaction mechanism between TRPV1 and the neuro-immune regulatory axis, and explored its potential as a therapeutic target for inflammatory diseases.

Objective To investigate the clinical efficacy and safety of Quhan Tongluo Formula in treating knee osteoarthritis（KOA） of cold-dampness obstruction pattern. Methods A retrospective study was conducted on 231 patients with KOA of cold-dampness obstruction pattern admitted to Dongfang Hospital,Beijing University of Chinese Medicine from December 2022 to December 2023. The patients were divided into an exposed group （105 cases） and a non-exposed group （126 cases） based on whether Quhan Tongluo Formula was applied. The exposed group received Quhan Tongluo Formula combined with celecoxib,while the non-exposed group received only celecoxib. Using propensity score matching based on the baseline data of the medical records,76 pairs （a total of 152 cases） were matched. The changes in Visual Analog Scale （VAS） scores,Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC） total scores,and traditional Chinese medicine （TCM） syndrome scores before treatment and at 2,4,and 6 weeks after treatment were compared between the two groups,and safety was evaluated. Results Before treatment,there were no significant differences in VAS scores or WOMAC pain scores between the two groups. After treatment,both groups exhibited significant reductions in VAS scores and WOMAC pain scores,with the exposed group demonstrating significantly greater reductions compared to the non-exposed group （P< 0.01）. The total clinical effective rate was significantly higher in the exposed group than in the non-exposed group （P< 0.01）. Conclusion The clinical application of Quhan Tongluo Formula combined with celecoxib demonstrated superior efficacy over celecoxib monotherapy in treating knee osteoarthritis of cold-dampness obstruction pattern. The combined regimen significantly reduced VAS scores,total WOMAC scores,and TCM syndrome scores,with marked improvements in long-term efficacy.

Pain management is an important component of military medical support during wartime.Early pain management for wounded soldiers can effectively alleviate pain, which is critical to maintaining combat effectiveness, promoting physiological and psychological recovery of wounded soldiers, preventing chronic pain, and helping them return to the battle field. In recent years, the U.S. Armed Forces have increasingly emphasized prehospital pain management. They have been updating the relevant pain management guidelines to establish a practical system in order to ensure that the pain of wounded soldiers is effectively controlled. This paper reviews the current research on prehospital pain management in the U.S. Armed Forces and summarizes the advanced and practical technologies for prehospital pain management. It provides references for research on prehospital pain management,and optimization of prehospital pain management strategies suited to China’s operational context, and for the design of related training programs.;

High partial pressure oxygen is widely used in the treatment of ischemic and hypoxic diseases and in diving. However, chronic inhalation of gas with high oxygen partial pressure can have a toxic effect on the body, that is, oxygen toxicity. The lung is one of the target organs where injury is the most pronounced and direct after exposure to high partial pressure oxygen. This article reviews the research progress in pathogenesis and diagnosis of pulmonary oxygen toxicity in the hope of providing a reference for related prevention and treatment.

At present, global health governance is entering a new reforming stage on its rules. The adoption of Amendments to the International Health Regulations（2005） at the 77th World Health Assembly in 2024 and the adoption of the WHO Pandemic Agreement at the 78th World Health Assembly in 2025 have become important interim achievements of this round of reform. Developed countries have always played a dominant role in rule-making in global health governance. In this round of reform, competition between developed and developing countries is becoming increasingly fierce, and developing countries including China are faced with significant challenges in playing their due roles in global health governance system. The key issues under dispute lie in genetic sequence data sharing, medical products availability, and international cooperation in core capacity building. United with other developing countries, China should make more constructive suggestions on advocating “conditional” sharing of genetic sequence date, promoting benefit-sharing obligations to be more substantive, and enhancing core capacity building of developing countries in the following reform process, promoting the construction of a human health community through practical actions.

Objective To investigate mutations in OTU domain-containing protein 3（OTUD3） and their functional mechanisms in the initiation and progression of colorectal cancer（CRC）. Methods Gene expression profiling interactive analysis （GEPIA2） and the human protein atlas database （THPA） were used to analyze gene transcription and protein expressions. Samples from 32 patients with CRC were collected to identify OTUD3 mutants. Based on the information about mutation sitesof OTUD3 in an existing database, a plasmid vector containing the OTUD3 gene mutant was constructed. Plasmid vectors containing the phosphatase and tensin homolog deleted on chromosome 10 （PTEN） and the OTUD3 gene mutant were co-transfected into HCT116 cells. Western blotting, half-life, immunoprecipitation, ubiquitination, and hybrid algorithm molecular docking （H-DOCK） assays were employed to find out whether and why the OTUD3 mutants affected PTEN protein levels.Functional alterations in CRC cells after OTUD3 mutation were verified by CCK-8 cell proliferation, transwell cell invasion, scratch, and clonal formation assays. Results OTUD3 mutations were highly frequent in CRC. OTUD3 mutants R178W and N321S resulted in the loss of function of the stable PTEN protein, leading to enhanced proliferation, invasion, migration, and survival of CRC. Conclusion In CRC, OTUD3 mutation reduces the ability to stabilize PTEN and promotes the occurrence and development of CRC.

On plateaus,the low-oxygen and low-pressure environment is likely to lead to cognitive impairments,negatively impacting individuals newly exposed to high altitudes. This paper reviews how high-altitude environments impair cognitive functions and explores protective strategies in terms of oxygen-enriched and pressurization technologies,neuroregulation techniques,and approaches to endogenous protection. It is recommended that future research focus on personalized cognitive protection and training,the construction of integrated protection systems based on multi-technology convergence,and the investigation of long-term effectiveness and sustainability. These efforts are expected to result in more comprehensive strategies for cognitive protection and enhancement in high-altitude operations.

In the era of rational molecular design of fusion proteins, linker selection has garnered significant attention as a critical determinant of construct functionality. Suboptimal selection of linkers may result in such structural perturbations as protein misfolding, reduced expression yields, and compromised bioactivity. Consequently, the strategic selection of linkers tailored to specific objectives of molecular design by optimizing spatial orientation, maintaining domain autonomy or enabling post-translational modifications has emerged as a pivotal research frontier. Given these challenges, this review outlines the common properties of linkers, ways of classification, and the functional-structural interplay in current applications. Furthermore, we propose context-dependent selection frameworks for therapeutic proteins, biosensors, and enzyme cascades, which can serve as a systematic methodology to guide linker optimization in next-generation fusion protein engineering.

This paper provides a survey of the research progress in and applications of radio frequency identification（RFID） technology in the entire process management of blood supply. This paper makes an in-depth analysis of the scenarios and effectiveness of the technology,focusing on such key operational stagesas donor management, health screening, blood collection and testing, component preparation, storage and distribution, and patient transfusion. Based on a comprehensive evaluation of current achievements and bottlenecks, this study offers strategies for optimization of RFID technology in the management of blood supply and gives recommendations. The findings are intended to provide data for the establishment of an intelligent and traceable modern blood management system.

Objective To investigate the roles and mechanism of deoxycholic acid （DCA） in mediating the neuroinflammatory responses induced by hypobaric hypoxia. Methods C57BL/6J mice were randomly divided into thecontrol group （Con）, tauroursodeoxycholic acid （TUDCA） group, hypoxia group （Hyp） and hypoxia+TUDCA group （Hyp+TUDCA）. The mice were exposed in a hypoxic chamber for 48 h, which could mimic the high altitude environment. The levels of total bile acids （BA）, lithocholic acid （LCA） and deoxycholic acid （DCA） in the serum and colon of mice were detected using enzyme-linked immunosorbent assay （ELISA）, so were levels of DCA in the cortex, hippocampus and hypothalamus. The role of DCA in inducing neuroinflammation and IL-1β and TNF-α expressions was evaluated by knocking down the DCA receptor, farnesoid X receptor （FXR） in the N9 microglial cells and by administrating TUDCA to mice followed by hypoxia exposure. Real-time quantitative PCR （qPCR） and immunofluorescence staining were used to detect the activation of microglia and expression levels of interleukin-1β（IL-1β） and tumor necrosis factor-α （TNF-α） in the cortex of mice in each group. Results Hypoxia exposure increased DCA levels in the colon, serum and cortex. Under the same conditions, cortical microglia were activated, along with the elevation of IL-1β and TNF-α levels. DCA treatment increased the expression levels of FXR, IL-1β and TNF-α in N9 microglial cells. Knocking down the expression level of FXR inhibited DCA-induced IL-1β and TNF-α expressions in N9 cells. Furthermore, administration of TUDCA inhibited microglial activation and elevation of IL-1β in the cortex induced by hypoxia. Conclusion DCA can serve as a mediator in neuroinflammation by activating FXR in the cortex under hypoxia exposure. TUDCA administration can be used to mitigate neuroinflammation induced by hypoxia.

Objective To assess the comprehensive effects of transcranial direct current stimulation （tDCS） on physical fitness in healthy athletes and non-athletes. Methods Two researchers independently retrieved PubMed, Embase, Web of Science, Scopus, the Cochrane Library, CNKI, Wanfang, and VIP databases, and collected experimental literature on the effects of tDCS on physical fitness from the database establishment to March 6, 2025. Reviewer Manager 5.4 software and Stata 18.0 software were used for Meta-analysis. Results Data from 40 studies involving 778 subjects was included in the Meta-analysis that revealed that tDCS significantly improved the physical fitness of subjects （SMD=0.15）. Specifically, anodal tDCS targeting the M1 area （SMD=0.17）, at the current of 1.5 mA or 2 mA （SMD=0.64; SMD=0.13）, maintained for 20 minutes （SMD=0.19）, and with a 35 cm⊃2; electrode patch （SMD=0.31） resulted in significant improvements in maximum strength （SMD=0.32）, explosive force（SMD=0.27）, muscle endurance （SMD=0.40）, cardiopulmonary endurance （SMD=0.51）, and static balance （SMD=0.34） in athletes （SMD=0.25） and non-athletes alike （SMD=0.13）. However, there was no significant effect on the moving speed and dynamic balance. Conclusion tDCS can effectively improve maximum strength, explosive power, muscle endurance, cardiopulmonary endurance, and static balance in healthy athletes and non-athletes.

高原地区受低氧、低温、复杂地形及极端天气影响,传统血液运输依赖专用运血车与运血箱,存在运输时效性差、设备故障率高、极端天气通行困难等突出问题。该文探讨了国内外无人机血液运输模式在高原特殊环境下的应用现状及潜力,系统梳理了高原无人机血液运输的设计要点与解决方案,为突破“最后一公里”血液配送难点和构建高海拔地区应急血液保障体系提供参考。

Infectious pneumonia caused by bacteria,viruses,or other pathogenic microorganisms remains a huge threat to human health. Immunocyte-derived biomimetic nano-drug delivery systems can be used for drug delivery by taking advantage of the natural anti-inflammatory effect of immune cells and thus show great potential in lung-targeted therapy. This review begins by introducing different types of immune cells in the lung. The preparation methods of immunocyte-derived biomimetic nano-drug delivery systems and their applications in bacterial pneumonia,viral pneumonia,acute respiratory distress syndrome and cytokine storms are also reviewed. The review is expected to provide data for the targeted therapy of infectious pneumonia.

In 2024, the U.S. Defense Advanced Research Projects Agency （DARPA） intensified its deployment and management of biotechnological defense applications that involved four major domains： combat effectiveness enhancement, biosecurity defense, development of military materials, and intelligent biotechnology. This paper conducts an in-depth analysis of DARPA′s 2024 biotech advancements to provide a reference for related research and development in China.

目的 分析罗布泊戈壁驻训军事人员2024年5-9月发病特点和病因,为卫勤保障资源的合理配置提供数据支持。方法 收集有效病例536例,涵盖性别、年龄、抵驻地日期、就诊日期及疾病诊断等信息,回顾性分析2024年5-9月罗布泊戈壁驻训军事人员初驻前4个月发病情况及病因。结果 罗布泊戈壁驻训军事人员病例数从第1个月（129例）持续增加至第4个月（149例）。前7位系统疾病是运动系统（29.85%）、消化系统（16.79%）、皮肤及皮下组织疾病（16.42%）、眼疾病（14.18%）、呼吸系统（8.77%）、中暑（4.85%）和失眠（3.92%）,占总病例数94.78%。前7位单一疾病是腰肌劳损（13.62%）、急性胃肠炎（7.46%）、结膜炎（5.03%）、干眼症（4.48%）、湿疹（4.10%）、踝外伤（3.73%）、急性上呼吸道感染（3.36%）,占总病例数41.79%。运动系统、眼疾病、中暑、失眠系统疾病及腰肌劳损、急性胃肠炎、结膜炎、干眼症单一疾病的发病与驻训时长有关（P<0.05）。结论 根据罗布泊戈壁地区驻训军事人员发病特点及病因,实施精准有效防治,对提升该地区卫勤保障的针对性和降低非战斗减员具有现实意义。

Objective To explore the neuroprotective effects of nicotinamide riboside against microwave radiation-induced brain injury in mice. Methods Mice were subjected to whole-body uniform microwave radiation （at a central frequency of 2.856 GHz,and average power density of 20 mW/cm⊃2; for 30 min）. After radiation,the mice received intraperitoneal injections of nicotinamide riboside chloride at doses of 250,500,or 1000 mg/（kg·d）. Behavioral performance was assessed using the open field test （OFT） and elevated plus maze （EPM）. Histopathological changes in the cortex （CTX）,hippocampus （HPC）,and hypothalamus （HT） were detected via hematoxylin-eosin （HE） staining. Levels of such pro-inflammatory cytokines as tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the CTX,HPC,and HT were measured using enzyme-linked immunosorbent assay （ELISA）. Proteomic analysis was performed to assess changes in protein expressions in the CTX. Results After microwave exposure,the exploratory behavior of mice was reduced,and the entries into the central zone and open arms were decreased （P<0.05）. Neuronal injuries were increased,and the levels of TNF-α and IL-6 were elevated （P<0.05）. Proteomic analysis indicated that differentially expressed proteins were mostly enriched through oxidative phosphorylation related pathways. NR interventions significantly ameliorated these alterations,as evidenced by increased exploratory behavior,reduced neuronal injury,decreased inflammatory cytokine levels （P<0.05）,and the reversal of expressions of dysregulated proteins,including zinc finger AN1-type domain-containing protein 5 （Zfand5）. Conclusion NR can alleviate brain injury and associated behavioral and neuroinflammatory alterations in mice induced by microwave radiation,which might involve the zfands and other key molecules.

With the increasing abuse of antibiotics, the development of rapid, accurate and sensitive methods for antibiotic detection has become critical. Nucleic acid sensors as new biosensors have shown great potential in the field of antibiotic detection due to their high selectivity, high sensitivity and real-time monitoring ability. This paper reviews the research progress in antibiotic detection based on nucleic acid sensors,including colorimetric, optical and electrochemical nucleic acid sensors, in the hope of providing a reference for the research and development of new types of antibiotic detection technologies based on nucleic acid sensors.

Objective To establish a rat model of acclimatization to motion sickness （MS） induced by rotational stimulation. Methods To determine the stimulation conditions of MS, SD rats were divided into a static control group （SCG） and a single rotation stimulation group （SRG） before being subjected to the motion sickness index （MSI） measurement, open-field experiment and Morris water maze experiment after rotational stimulation to verify the feasibility of MS being induced in rats. Morris water maze experiments were performed to find out whether rotational stimulation could be used to induce MS in rats. During experiments on acclimatization, the SD rats were divided into the control group （Ctrl）, one day of rotational stimulation group （Day1）, three days of continuous rotational stimulation group （Day3）, and seven days of continuous rotational stimulation group （Day7） before the changes in the MSI and behavior of these rats were recorded so as to explore the relationship between continuous stimulation and MS acclimatization in rats. Results After rotational stimulation, the rats showed a significant increase in the number of fecal pellets （P<0.0001） and in the MSI （P<0.0001） compared with the SCG.In the open field experiment, the rats showed a significant decrease in the spontaneous activity time （AT） （P<0.0001）, total spontaneous activity distance （TD） （P<0.001） and distance moved by the center point per second （DMCPS） （P<0.001）. The time taken to climb onto the platform （latency to find the platform, LP） （P<0.0001） and the total distance to the platform （distance to the platform, DP） （P<0.001） were significantly increased during the Morris water maze experiment. Acclimatization experiments revealed a significant increase in MSI and in the number of fecal pellets in the Day1 and Day3 groups of rotational stimulation compared to the Ctrl group （P<0.0001）. AT （P<0.01）, TD （P<0.05） and DMCPS （P<0.01） were significantly decreased, while LP and DP were significantly increased （P<0.0001）, but there was no statistically significant difference in indices compared with the Day7 group（P>; 0.05）. Conclusion Sinusoidal stimulation can induce MS in rats, and twice-a-day, continuous rotational stimulation for seven days can lead to acclimatization. The rat MS model can be assessed via behavioral experiments.

Objective To establish a rapid detection method for Clostridium botulinum in food. Methods A rapid detection method based on RPA-CRISPR/Cas12a was developed by integrating recombinase polymerase amplification （RPA） with the CRISPR-Cas12a system. After the reaction conditions were optimized,the method′s sensitivity,specificity,and usefulness were methodically confirmed. Results and Conclusion The optimized method achieved detection within 1 hour,with a limit of detection （LOD） of 1.91 copies/µL. No cross-reactivity was observed with non-target pathogens. The RPA-CRISPR/Cas12a-based detection method developed in this study exhibits high specificity,sensitivity,and operational simplicity and may provide a feasible solution for the rapid detection of foodborne pathogens.

Objective To investigate the feasibility of using the cell-free DNA （cfDNA） carrying tissue-specific mutations as biomarkers for assessing the severity of exercise-induced tissue injury. Methods Based on a public gene expression database, ten tissue-specific and highly-expressed genes were selected for each of ten different human tissues. A total of 34 young healthy volunteers were recruited, and their peripheral blood samples were collected after running 5 km per day for one week. Genomic DNA from leukocytes, plasma exosomal RNA, and plasma cfDNA were extracted and subjected to high-throughput sequencing respectively. Tissue-specific somatic mutations in plasma exosomal RNA were identified, and the relationship between cfDNA carrying these mutations and traditional protein biomarkers was analyzed. Results Tissue-specific cfDNA mutations related to five tissues （myocardium, skeletal muscle, intestine, stomach, and kidney） were detected in more than five volunteers. The correlation coefficients between total plasma cfDNA levels and the levels of tissue-specific protein biomarkers associated with these five tissues were less than 0.3 （n=34, r=-0.51-0.28, P=0.0022-0.65）. Notably, for each specific tissue, the levels of tissue-specific cfDNA mutations were positively correlated with the corresponding protein biomarker levels, and correlation coefficients were over 0.8 （n=7-13, r=0.81-0.92, P=9.0× 10^-4-0.020）. Conclusion Tissue-specific cfDNA mutations may serve as novel potential biomarkers for non-invasive evaluation of exercise-related tissue injury.

Objective To investigate the clinical manifestations of traditional Chinese medicine （TCM） and their associations with TCM constitutions in individuals who have migrated to plateau areas,and to provide a scientific basis for plateau health management. Methods Migrants living in areas above 3000 m were selected as research subjects. Data were collected by using TCM symptom assessment scales and constitution assessment scales. Descriptive statistical analysis was conducted to determine the incidence and severity of symptoms among individuals with different migration durations,and core symptoms were identified. Factor analysis was performed by using SPSS software to extract symptom clusters and explore the correlation between core symptoms and TCM constitutions. Results Among individuals who migrated to plateau areas,the incidence of discomfort symptoms was 83.44%. The five most common symptoms were dry skin （67.94%）,forgetfulness （56.03%）,dry mouth （52.06%）,yellow urine （48.73%）,and insomnia （47.14%）. In the top 10 symptoms with the highest increase in incidence,yellow urine （33.51%） and forgetfulness （26.33%） were both present in the top 10 symptoms across different migration durations. Factor analysis extracted 5,2,4,and 6 symptom clusters from the overall population,individuals who migrated within 1 year,those who migrated for 1-2 years,and those who migrated over 2 years,respectively. Qi-deficiency constitution （QDC）,blood stasis constitution （BSC）,qi stagnation constitution （QSC）,phlegm-dampness constitution （PDC）,and dampness-heat constitution （DHC） were significantly positively correlated with forgetfulness. Conclusion Migrating to plateau areas can induce discomfort symptoms,and both the number and incidence of symptoms increase with longer migration durations. The number and incidence of high-frequency symptoms （incidence≥30%） increase with prolonged migration time. There are differences in the composition and severity of symptom clusters across different migration durations. QDC,BSC,QSC,PDC,and DHC are closely related to forgetfulness and can be considered risk constitutions for forgetfulness. Timely attention to changes in symptom clusters and constitutions can help prevent and mitigate the occurrence and development of symptoms.

目的 军事无人机操作具有远程操控、轮班作业、长时间飞行等作业特点,操作人员容易产生疲劳、失眠、睡眠不足和睡眠质量降低等问题。对军事无人机操控员的睡眠质量和疲劳状况进行调查,为采取干预措施提供理论依据。方法 随机抽取无人机操控员107例,采用匹兹堡睡眠质量指数量表（PSQI）和疲劳量表（FS-14）对睡眠质量和疲劳状态进行评估。结果 无人机操控员睡眠障碍检出率为28%;PSQI总分为（6.21±2.67）分,显著高于国内普通成人群和歼击机飞行员（P<0.01）,但与运输机飞行员得分无统计学差异（P>0.05）;高原地区无人机操控员PSQI总分显著高于平原地区（P<0.05）。无人机操控员在体力疲劳、脑力疲劳和疲劳总分3个维度均低于歼击机飞行员,但无统计学差异（P>0.05）。相关分析结果显示,PSQI总分与体力疲劳、脑力疲劳和FS-14疲劳总分均呈显著正相关。结论 军事无人机操控员睡眠状况需重点关注,不同飞行作业类别对睡眠和疲劳的影响程度不同,有必要开展战训现地客观检测及相关保障措施研究。

Objective To profile ubiquitination in cysteinyl aspartate-specific proteinase-2（CASP2） deficient cells under heat shock and investigate the role of CASP2 in stress response. Methods Ubiquitination levels in subcellular fractions of control and CASP2 knockout （KO） cells were detected via Western blotting. After 2 hours of heat shock treatment, Soluble Ⅱ and Pellet fractions were collected from both control and CASP2 KO cells for ubiquitinome analysis. Anti-di-glycine remnant （K-ε-GG） antibody-based proteomic analysis was performed to identify differentially ubiquitinated proteins and associated key signaling pathways. Proteins that displayed significantly upregulated ubiquitination in CASP2 KO cells under heat shock were subjected to His-tag pull-down assays to find out whether CASP2 regulated the ubiquitination of these proteins. Results Under heat shock, CASP2 KO cells displayed significantly higher accumulation of overloaded ubiquitinated conjugates in the Pellet fraction compared to controls. Ubiquitinomics analysis revealed substantial alterations in protein ubiquitination patterns following CASP2 KO. One hundred proteins exhibited significantly elevated ubiquitination levels while 36 proteins had their ubiquitination reduced relative to controls. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis indicated that hyper-ubiquitinated proteins were primarily associated with Huntington disease, Alzheimer disease, bile secretion, carbon metabolism and autophagy. His-tag pull-down assays combined with Western blotting revealed increased ubiquitination of nicotinamide adenine dinucleotide reduced - ubiquinone oxidoreductase 1 beta subcomplex subunit 3 （NDUFB3） and autophagy-related protein 9A （ATG9A） in CASP2 KO cells under heat shock. Conclusion Overloaded ubiquitinated conjugates are accumulated due to CASP2 deficiency during heat shock. CASP2 modulates ubiquitination levels through multiple signaling pathways.

Objective To heterologously express and purify the small ubiquitin-like modifier （SUMO） tag fused organophosphorus hydrolase mutant H257Y/L303T （YT）,namely SUMO-YT,and evaluate its hydrolytic capacity against ethyl paraoxon and soman. Methods The SUMO tag encoding gene was constructed at the N-terminus of the YT encoding gene with a linker sequence via enzyme digestion and ligation before SUMO-YT was expressed in Escherichia coli. SUMO-YT and YT were purified through ammonium sulfate precipitation and affinity chromatography to obtain high-purity target proteins. The activity and kinetic parameters of the recombinant enzymes were examined using ethyl paraoxon and soman as substrates. Results The system for expression and purification of recombinant enzymes was established,yielding SUMO-YT and YT,and the former exhibited more significantly enhanced hydrolytic efficiency than the latter,with catalytic rates 11-fold higher for paraoxon and 4.4-fold higher for soman. At 37 ℃ and pH 7.2,SUMO-YT reduced the inhibition rate of acetylcholinesterase （AChE） by soman from 100% to 45.7% within 3 minutes,whereas YT reduced it to no more than 80%. Conclusion The high-activity recombinant SUMO-YT is prepared. SUMO tag fusion can significantly enhance the hydrolytic capacity of YT against ethyl paraoxon and soman.

Objective To enhance the cyclic peptide compound's membrane permeability, structural stability, and neuroprotective activity, based on the amino acid sequence of peptides of Tat-GluA2-3Y, by designing and synthesizing a serial of cyclic peptides through strategies including polypeptide cyclization, replacement of the cell-penetrating peptide, substitution with D-amino acids, and incorporation of mini polyethylene glycol fragments. Methods The target peptides were synthesized based on standard Fmoc solid-phase method, followed by analysis and purification via reverse phase high-performance liguid chromatography （RP-HPLC）. The cytoprotective activity of the peptides was evaluated by using the HT-22 cell model. The transmembrane transport efficiency of the peptides was determined based on the Caco-2 monolayer intestinal epithelial cell model. Plasmatic plasma and metabolic stability of the peptides were measured by in vitro co-incubation experiments with rat plasma and human liver microsomes. Finally, the in vivo neuroprotective activity of the peptides was validated by using a mouse middle cerebral artery occlusion model. Results Seven cyclic peptides were successfully designed and synthesized by using the standard Fmoc solid-phase method, with purities exceeding 90% as confirmed by RP-HPLC. Cytoprotective activity assay demonstrated that both Tat-GluA2-3Y and CMT-C3Y exhibited activity at concentrations above 125 nmol/L, with CMT-C3Y showing superior activity as compared to Tat-GluA2-3Y. The results of the transmembrane assay demonstrated that, compared to Tat-GluA2-3Y, CMT-C3Y exhibited significant transmembrane capabilities at all tested concentrations （P<0.001）. CMT-C3Y was classified as a highly permeable compound, whereas Tat-GluA2-3Y was categorized as a moderately permeable compound. Plasma stability studies indicated that over 50% of Tat-GluA2-3Y was metabolized after 4 h of co-incubation with rat plasma. After 8 h of coincubation with CMT-C3Y, the remaining amount was 88.1%, and no obvious degradation phenomenon occurred. In human liver microsomal stability tests, the half-life of Tat-GluA2-3Y was 26.1 min, as compared to 103.8 min for CMT-C3Y, highlighting the enhanced stability of CMT-C3Y. Tat-GluA2-3Y and CMT-C3Y were classified as a fast-metabolizing drug and a moderate-metabolizing drug, respectively. Animal experiments further demonstrated that at a dose of 8 mg/kg the neuroprotective activity of CMT-C3Y was significantly superior to that of Tat-GluA2-3Y （P<0.001）. Conclusion The designed bicyclic peptide CMT-C3Y demonstrates significantly higher cell-penetrating efficiency and superior plasma stability as compared to Tat-GluA2-3Y, along with enhanced neuroprotective activity at both cellular and animal levels.

Objective To investigate the direct stimulatory effects of calprotectin S100A8/A9 on hepatic stellate cells （HSCs） and underlying regulatory mechanisms. Methods Primary HSCs of mice were stimulated with S100A8/A9 heterodimer recombinant protein at 200 and 1000 ng/mL. Data on quantitative proteomics was obtained using the tandem mass tag （TMT）-labeled method before changes in the protein level of HSCs were analyzed. Differentially expressed proteins （DEPs） were screened using Significance B method and P< 0.05, followed by Reactome pathway enrichment analysis. Furthermore, protein-protein interactions between the DEPs enriched in the pathways were analyzed using the STRING database. Results The protein expression profile of HSCs was significantly altered after treatment with S100A8/A9 at 1000 ng/mL. Reactome pathway enrichment analysis revealed significant enrichment in such pathways as transforming growth factor-beta （TGF-β） signaling, nuclear factor kappa-B （NF-κB） signaling activation, cytokine-mediated immune regulation, and collagen biosynthesis. The analysis of protein-protein interactions identified NF-kappa-B transcription factor subunit （RELB）, chemokine （C-X-C motif） ligand 10 （CXCL10） and Notch receptor 1 （NOTCH1） as key hub proteins in the regulatory network. Conclusion S100A8/A9 can directly stimulate the activation of HSCs, through NF-κB signaling, TGF-β signaling, and Notch signaling pathways potentially. This study sheds light on the mechanisms underlying the activation of HSCs stimulated by S100A8/A9.

Objective To investigate the biological function and potential mechanisms of long non-coding RNA （lncRNA） neurensin 2-antisense RNA 1 （NRSN2-AS1） in liver cancer cells. Methods The Encyclopedia of RNA Interactomes （ENCORI） database was used to analyze the expression levels of NRSN2-AS1 in liver cancer tissues and normal tissues as well as its association with the prognosis of patients. Stable lncRNA NRSN2-AS1 cell lines, overexpressed or knockdown, were constructed. The effects of NRSN2-AS1 on tumor cell proliferation were explored using CCK-8 and colony formation assays. Transwell and wound healing assays were employed to examine the role of NRSN2-AS1 in tumor cell migration and invasion. The impact of NRSN2-AS1 on tumor cell aerobic glycolysis was assessed by measuring hexokinase activity, glucose uptake, ATP and etracellular lactate levels. Quantitative real-time PCR （qPCR） and Western blotting were used to evaluate the effects of NRSN2-AS1 on the mRNA and protein expression levels of hexokinase 2 （HK2） in tumor cells. Results Analysis from the ENCORI database revealed that NRSN2-AS1 was upregulated in liver cancer tissues compared to normal tissues, and that high expressions of NRSN2-AS1 were closely associated with poor prognosis of patients. In vitro functional assays demonstrated that overexpression of NRSN2-AS1 promoted proliferation, migration, and invasion of liver cancer cells, and enhanced glycolysis levels while knockdown of NRSN2-AS1 inhibited these processes and suppressed glycolysis. Furthermore, overexpression of NRSN2-AS1 increased the mRNA and protein levels of HK2 while knockdown of NRSN2-AS1 decreased HK2 expression in liver cancer cells. Conclusion NRSN2-AS1 is highly expressed in liver cancer tissues, and it may promote liver cancer progression by enhancing HK2 expression and aerobic glycolysis.

Objective To find out about perceived stress, self-compassion, cognitive flexibility, and depression among young males at high altitudes, construct a relational model between perceived stress and depression, explore the relationship between perceived stress and depression, and examine the roles of self-compassion and cognitive flexibility. Methods Using the convenient sampling method, 733 young males from a high-altitude unit were surveyed via the general information questionnaire, the Chinese Perceived Stress Scale （CPSS）, the Cognitive Flexibility Inventory （CFI）, Self-Compassion Scale （SCS） and Center for Epidemiologic Studies Depression Scales （CES-D）. Results （1）The CES-D score was 13.92±; 3.38. （2）Perceived stress was positively correlated with depression （r=0.28,P< 0.01）. （3）Self-compassion partially mediated the relationship between perceived stress and depression, accounting for 59.05% of the total effect. （4）Cognitive flexibility moderated the relationship between self-compassion and depression （P< 0.05）. Conclusion Young males at high altitudes exhibit notable levels of depressive symptoms. Perceived stress was significantly positively correlated with depression.By enhancing self-compassion and cognitive flexibility, the incidence of depressive symptoms among young males in prolonged high-stress conditions can be reduced.

Uncontrolled hemorrhage is the leading cause of potentially survivable combat casualty death,dominated by non-compressible hemorrhage in the torso and junctional areas. Rapid hemostasis using war trauma dressings is the mainstay of treatment for such casualties. The article reviews the research progress of novel hemostatic dressings for war trauma,including novel improved dressings,multifunctional dressings,electrospinning wound dressings,and smart dressings in order to provide references for the research on war trauma dressings.

Objective To investigate the effects of intermittent microwave irradiation on pathological structure and cognitive function of Alzheimer’s disease （AD） mice. Methods Forty C57BL/6J mice and another forty 5×FAD mice were randomly divided into the sham irradiation （sham-WT）,irradiation （MW-WT）,AD sham irradiation （sham-AD）,and AD irradiation （MW-AD） groups,with 20 mice in each. Mice underwent daily 1-hour microwave irradiation （900 MHz,40 Hz repetition rate） on an intermittent schedule： 2 weeks on,2 weeks off,and 2 weeks on again. The cognitive function of mice was assessed via behavioral experiments conducted both immediately and six weeks after irradiation. The expressions of phosphorylated tau（p-Tau） and β amyloid protein （Aβ） plaques were detected via immunofluorescence. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of key enzymes involved in Aβ production and neuroinflammatory factors in the brain tissue. Results Compared with the sham-WT group,the novel object recognition index and the novel arm recognition index in the sham-AD group were significantly reduced（P<0.05）, but those were significantly increased in the MW-AD group compared to the sham-AD group （P<0.05）. In addition,the levels of p-Tau and Aβ proteins in the brain of the MW-AD group were significantly decreased （P<0.05） while the levels of β-secretase and γ-secretase in the cortex were significantly increased （P<0.05）. The levels of CD68,tumor necrosis factor-α （TNF-α）,and interleukin-10 （IL-10） were also increased to varying degrees （P<0.05）. Conclusion Intermittent microwave irradiation （900 MHz,40 Hz） can ameliorate cognitive deficits and attenuate Aβ and p-Tau pathology in AD mice rather than inhibit the key secretases involved in Aβ production or the occurrence of neuroinflammation.

Heart failure （HF） is a cardiovascular disease with a high prevalence and mortality rate worldwide, and despite the widespread use of existing drugs, device intervetions and surgical procedures, the clinical outcomes are still unsatisfactory.The exploration of new methods to treat HF is still an urgent problem. Gene therapy provides a new therapeutic strategy for HF by targeting the regulation of pathogenic genes. This article systematically reviewed the delivery system optimization, key targets and clinical translational challenges of gene therapy for HF, aiming to provide a theoretical basis for the optimization of treatment strategies.

Objective To explore the role of dapansutrile （OLT1177） in radiation-induced intestinal injury and the mechanism. Methods C57BL/6J mice were locally irradiated in the abdomen with ⁶⁰Co to induce a model of radiation-induced intestinal injury. OLT1177 was intraperitoneally injected at a dose of 100 mg/kg 2 hours before irradiation and 6 hours after irradiation before the drug was administered once a day. At 12 hours after irradiation, intestinal tissues were taken for terminal deoxynucleotidyl transferase mediated nick end labeling（TUNEL） staining to detect apoptosis in intestinal tissues. At 4 days after irradiation, mouse serum was collected to detect the levels of inflammatory factors in the serum. Hematoxylin-eosin （HE） stainingwas used for the evaluation of the damage to the intestinal villus structure. Immunohistochemical staining was adopted to detect the changes in crypt proliferation in intestinal tissues. Finally, proteins were isolated from intestinal tissues, and Western blotting was employed to evaluate the activation of nucleotide-binding oligomerization domain-like receptor protein 3（NLRP3） inflammasome. Results After irradiation, the intestinal villi in mice were shortened. Meanwhile, there was a notable declinein the number of cells that were proliferating in the crypts, a surge in the number of apoptotic cells, and a significant spike in the overall inflammatory level. However, administration of OLT1177 inhibited the activation of the NLRP3 inflammasome, reduced apoptosis and pyroptosis, decreased the inflammatory level, and thus improved radiation-induced intestinal injury. Conclusion Administration of OLT1177 can significantly mitigate radiation-induced intestinal injury.

Osteoporosis is a globally prevalent metabolic bone disease, with bone homeostasis imbalance being its key pathogenic mechanism. Over the years, studies on the relationship between ambient temperature and bone health have shown heterogeneous results due to different conditions. Epidemiological studies indicate that the incidence of osteoporotic fractures varies geographically and climatically. People in cold regions experience earlier bone loss, and high-latitude cold areas are high-risk zones for hip fractures. Osteoporosis is more prevalent in North China that in South China. Additionally, the early stage of the disease is insidious, highlighting the need for early prevention and treatment across the entire population. Mechanistically, low temperatures affect acral bone development, reduce bone blood circulation, cause degradation of bone microstructure, and increase osteocyte apoptosis, thereby promoting bone resorption and reducing bone mass. This review aims to provide data and new lines of thought for the early precise prevention and effective clinical treatment of osteoporosis in cold regions.