The unique geography,climate,and natural conditions of plateaus pose significant challenges to the physical health and combat effectiveness of stationed troops.In high-altitude regions,maladaptation can lead to acute mountain sickness,such as high-altitude pulmonary edema and high-altitude cerebral edema.Previous studies have shown that gradual acclimatization is an effective strategy for preventing and mitigating altitude sickness.Additionally,non-pharmacological strategies such as intermittent hypoxia and pre-simulated altitude training have also been proven to effectively promote altitude acclimatization.Conventional acclimatization strategies take longer time and are not conducive to rapid deployment of military personnel.In this article,we review various acclimatization training for individuals entering high-altitude areas,in order to provide a reference for the research and application of scientific and efficient altitude acclimatization training strategies.

Objective To analyze the risk factors for chronic mountain sickness(CMS)in young male migrants living in high-altitude areas and to construct a diagnostic model and evaluate its diagnostic efficacy.Methods From June 10 to December 29,2023,a cross-sectional study was conducted on young male migrants subjected with convenience sampling who had been living in high-altitude areas(4 500～5 000 m)for 6 months or longer.Their demographic data were collected and blood samples were collected for laboratory test.According to the Qinghai Score for Chronic Mountain Sickness,they were divided into CMS group and non-CMS group.Then the participants were randomly divided into a training set and a test set in a ratio of 8∶2.Independent risk factors for CMS occurrence were screened out,through random forest variable importance ranking,univariate and multivariable logistic regression analysis,and a diagnostic model was constructed based on these factors.Receiver operating characteristic(ROC)curve analysis,calibration curve analysis,clinical decision curve analysis,and influence curve analysis were used to comprehensively evaluate the diagnostic performance of the model.Results According to the inclusion and exclusion criteria,308 out of 376 participants were finally subjected,and 17.53%of them were diagnosed with CMS.The major clinical symptoms of the CMS patients were dyspnea or palpitations(79.63%)and sleep disorders(85.19%).Further analysis revealed that creatine kinase-MB/creatine kinase(CK-MB/CK,OR=2.17,95%CI:1.43～3.28),high-altitude residence time(OR=2.44,95%CI:1.08～5.54),and body mass index(BMI,OR=1.62,95%CI:1.05～2.50)were 3 major independent risk factors for CMS.The area under the curve(AUC)value of the CMS diagnostic model in the training set and test set was 0.821(95%CI:0.756～0.886)and 0.821(95%CI:0.700～0.944),the specificity was 66.30%and 73.90%,the sensitivity was 89.50%and 81.20%,respectively,indicating good discrimination ability.Hosmer-Lemeshow goodness-of-fit test showed consistency between predicted results and actual observations(χ2=10.029,P=0.263;χ2=4.477,P=0.812).Clinical decision curve analysis demonstrated that within the threshold probability range from 0.1 to 0.7,the net benefit of the model exceeded both full intervention and no intervention strategies.The influence curve analysis showed high consistency between the model predictions and actual incidence when the threshold probability exceeded 0.4.These two analyses together confirmed the clinical application value of the model.Conclusion CK-MB/CK,high-altitude residence time and BMI are independent risk factors for CMS,and their diagnostic model helps identify potential individuals at risk for CMS.Early intervention can prevent the harm of CMS to the health of young men migrating to high-altitude areas.

Objective To construct risk models for predicting the occurrence of high altitude de-acclimatization syndrome(HADAS)in the population returning from the plateau to the plain based on different machine learning algorithms and validate the predicting efficiency of these models.Methods Field or online surveys were conducted on the individuals who had ended their high-altitude living and returned to the plain areas from November 2020 to February 2024.Basic information,chronic mountain sickness(CMS),HADAS symptoms and other data were collected.With the inclusion and exclusion criteria,totally 1 095 individuals were subjected and assigned into the modeling group.Positive events were defined as HADAS score>5.Then the modelling group was divided into a training set(n=766)and an internal test set(n=329)in a 7∶3 ratio.Least absolute shrinkage and selection operator(LASSO)regression was used to select independent variables.Risk prediction models for high-altitude adaptation symptoms were built based on 8 machine learning methods,including multiple factor logistic regression(LR),decision tree(DT),random forest(RF),eXtreme gradient boosting(XGB),support vector machine(SVM),K-nearest neighbor(KNN),light gradient boosting(LGB)and na?ve bayes(NB).The models were compared and evaluated using receiver operating characteristic(ROC)curves,calibration curves and confusion matrices in the internal test set.The final model was presented using a nomogram or Shapley additive explanations(SHAP)algorithm.In August 2024,another 132 individuals who returned to the plains and met the same criteria were recruited and served as the external validation group.Results There were 549 individuals(50.14%)out of the 1 095 subjects having HADAS symptoms.LASSO regression identified CMS score,age and duration of high-altitude residence as significant predictors.Among the 8 machine learning algorithms,the LR model was identified as the best,with an area under the curve(AUC)value of 0.819(95%CI:0.789～0.850)and 0.841(95%CI:0.799～0.884),and an F1 score of 0.801 in the internal test set,respectively,and the AUC value and F1 score of the LR model were the largest among the 8 models in the internal test set.Spiegelhalter Z test of the calibration curve of the LR model indicated that its P=0.703 in the training set while P=0.281 in the internal test set.The AUC value of the LR model was 0.867(95%CI:0.765～0.969)in the external validation set.Conclusion The LR model constructed based on indicators including CMS score,age and duration of high-altitude residence has a good overall performance in the internal test set,and good discriminating effect in the external validation set.The constructed nomogram is convenient for application.

Objective To explore the characteristics of military training injuries in high-altitude troops and determine the possible impact of daily diet on these training injuries in order to provide theoretical reference for scientific training and medical service support for high-altitude troops.Methods A cross-sectional scheme was adopted in this study.A self-designed Military Training Injury Questionnaire for Plateau Troops was used to survey the officers and soldiers from resident high-altitude troops in July 2024 for their training injuries,daily diet,and other situations.The obtained data were statistically analyzed.Results Among the 3 655 participants,the incidence of military training injuries was 17.87%.The subject with highest incidence was physical training(45.94%),the most common season was winter(31.39%).The most common sites of injury were waist(28.48%),knees(22.21%),and ankles(18.07%),and the most common types were sprains(28.48%),chronic fatigue injuries(18.38%)and strains(12.25%).The intake amounts of coarse grains and potatoes,bean products,aquatic products and nuts were relatively low in the daily diet of high-altitude troops.Multivariate logistic regression analysis found intake of fruit(OR=0.625,95%CI:0.508～0.768,P<0.001)and of nut(OR=0.759,95%CI:0.654～0.879,P<0.001)were correlated with the occurrence of training injury.Conclusion The occurrence pattern of military training injuries in high-altitude troops in this survey is basically consistent with that of previous reports,but the incidence rate is slightly decreased.Regular consumption of fruit and nut may be protective factors for the occurrence of training injuries.

Objective To investigate the effects of plateau hypoxia on the growth and tumor microenvironment of colorectal carcinoma in vivo.Methods A total of 16 male BALB/C mice(6 weeks old,weight 18-20 g)were randomly divided into plateau hypoxic group and plain normoxic group,with 8 mice in each group,while 14 male C57BL/6 mice were grouped in same way,with 7 mice in each group.The mice in the plateau hypoxic group were housed in a low-pressure oxygen(10%)chamber to simulate an altitude of approximately 5 600 m,while the mice of the other group was maintained in SPF-grade normal atmospheric conditions(21%oxygen,at an altitude of about 300 m).Colorectal tumor MC38 cells and colon adenocarcinoma CT26 cells were subcutaneously implanted into C57BL/6 mice and BALB/C mice,respectively to construct subcutaneous tumor-bearing mouse models.Then the tumor size and weight were measured in 4 groups of mice.After the tumor tissues,spleen and blood samples were collected in the C57BL/6 mice.Flow cytometry was used to determine the percentages of macrophages,T lymphocytes,IFN-γ+T lymphocytes,and myeloid-derived suppressor cells(MDSC).The differences in these immune cells were compared between the cells from the plateau hypoxic group and those from the plain normoxic group.Results The weight of subcutaneous tumor mass was significantly inhibited in both C57BL/6 and BALB/C mice from the plateau hypoxic group than those from the 2 plain normoxic groups(0.17 vs 0.09 g,1.38 vs 0.51 g,P<0.01).When compared with the immune cells from the tumor mass of the plain normoxic C57BL/6 mice,the percentage of M2-type macrophages was reduced in the tumor tissue from the plateau hypoxic mice(22.13%vs 15.90%,P<0.05),so was that of MDSC(2.06%vs 1.05%,P<0.01),particularly in the monocytic(M)-MDSC subgroup(60.97%vs 41.13%,P<0.01).While,no significant change was observed in the proportion of the polymorphonuclear(PMN)-MDSC subgroup(10.97%vs 9.70%,P>0.05).Additionally,the percentage of CD4+T cells was significantly reduced(48.70%vs 41.93%,P<0.05),whereas that of CD8+T cells was obviously increased(41.25%vs 51.18%,P<0.05),along with a notable rise in the proportions of IFN-γ+T,IFN-γ+CD4+T and IFN-γ+CD8+T cells(28.58%vs 59.65%,23.33%vs 53.65%,36.9%vs 66.48%,P<0.01).However,between the peripheral blood samples of the 2 groups of C57BL/6 mice,the proportions of M1-type macrophages and CD4+T cells were reduced(84.98%vs 78.43%,5.86%vs 4.01%,P<0.01),and those of MDSC and PMN-MDC were increased(4.47%vs 16.43%,36.56%vs 62.97%,P<0.01).In the spleen tissues,notable decreases were observed in the proportions of CD8+T cells and IFN-γ+CD8+T cells between the 2 groups(33.05%vs 27.68%,5.13%vs 1.58%,P<0.01).Conclusion Plateau hypoxia improves the immune response within the tumor microenvironment,and inhibits subcutaneous tumor growth of colorectal cancer,but suppresses systemic immune response.

Objective To investigate the expression profile of cell adhesion molecular 3(CADM3)on pulmonary endothelial cells,analyze its role in mediating specific adhesion to monocyte,and explore a new mechanism of hypoxia inducing peripheral monocyte infiltration in pulmonary vessels.Methods Human umbilical vein endothelial cells(HUVEC),rat pulmonary vascular endothelial cells(rPEC),and rat aortic endothelial cells(rAEC)were subjected,and divided into normoxic(21%O2)control group and hypoxic(1%O2 or 5%O2)treatment group.Analyzing the transcriptome data of HUVEC exposure to hypoxia for 8 h screened a differentially expressed molecule,CADM3.Cell adhesion experiments,siRNA interference,immunohistochemical assay,Western blotting,and flow cytometry were used to study the role of CADM3 in hypoxia specific high adhesion of HUVEC monocytes.Iron chelator deferoxamine(DFX)and shRNA interference were employed to enhance the expression of HIF-1α,and the effect of HIF-1 transcriptional activity on CADM3 expression was analyzed.Results Hypoxic treatment resulted in enhanced expression of CADM3 in HUVEC,and the expression level reached the peak at 6-8 h after hypoxia,and then decreased.Transfection with siRNA targeting CADM3 decreased the expression of CADM3,and significantly reduced the adhesion rate of hypoxic HUVEC-U937 cells when compared with the negative control group(P<0.05).Compared with the solvent control group,the protein levels of HIF-1α and its target protein STC2 in HUVEC treated with DFX(100 μmol/L)were increased.Transfection with shRNA targeting HIF-1α led the protein levels of HIF-1α and its target protein STC2 decreased,but had no effect on the protein expression of CADM3 in comparison to the negative control group.The protein level and distribution of CADM3 on the cell membrane were increased in hypoxic rPEC.No expression of CADM3 protein was found in the rAEC when compared with rPEC.After treatment with 5 μg/mL LPS,there were no significant changes in HIF-1α,STC2 and CADM3 in rPEC cultured under normoxia or hypoxia.The adhesion rate between hypoxia rPEC with CD11b+cells was the highest,with statistical significance(P<0.01).After incubation with anti-CADM3 antibody,the adhesion of hypoxic rPEC-U937 was significantly decreased compared with the solvent control group(P<0.05).Conclusion Hypoxia specifically induces the expression of CADM3 in pulmonary vascular endothelial cells in a HIF-1-independent manner,and promotes the specific adhesion of pulmonary vascular endothelial cells and monocytes induced by hypoxia.

Objective To investigate the role of circular RNAs(circRNA)in Alzheimer's disease(AD)and its potential mechanism.Methods Six-month-old APP/PS1 mouse model of AD and wild type(WT)mice were subjected and then randomly divided into WT group,WT+circ-Olfm1 knockout group,AD group(transgenic APP/PS1 mice),AD+circ-Olfm1 knockout group,AD+FOXO3a knockout group,with 3 mice in each group.① The total RNA of mouse brain was extracted,and the differential expression of circRNAs and mRNAs between the AD mice and WT mice was detected,and the obtained circRNAs and mRNAs were analyzed with gene ontology(GO)analysis.② RT-qPCR was used to detect the expression of the top 10 up-regulated and down-regulated circRNAs,as well as the expression of circ-Olfm1 and miR-330-5p.③ Lentiviral vectors were prepared and stereotaxically injected into the cortex or hippocampus of WT and AD mice to knock out circ-Olfm1 gene.Water maze test was used to evaluate the effect of circ-Olfm1 knockout on cognitive function,and immunofluorescence assay was employed to observe the deposition of amyloid β(Aβ)plaque in the brain.④ The interaction between circ-Olfm1 and miR-330-5p was verified by double luciferase reporter gene analysis.⑤ The protein levels of AMPK and FOXO3a were detected by Western blotting.⑥ Transmission electron microscopy was utilized to observe the mitochondria of the hippocampus.⑦ The levels of inflammatory factors IL-6,IL-1β and TNF-α were detected by ELISA.Results There were totally 52 differentially expressed circRNAs identified between the AD and WT mice,including 28 up-regulated and 24 down-regulated(fold change>1.5,P<0.05).These differentially expressed genes are mainly involved in signal transduction,learning and memory and other functions.circ-Olfm1 was identified as the most significantly differentially expressed circRNA,which is highly expressed in the neurons and up-regulated in the cerebral cortex and hippocampus of the AD mice.Knockout of circ-Olfm1 reduced the number of Aβ plaques in the cerebral cortex and hippocampus of AD mice(P<0.01).In starBase database,there are complementary sequences observed between circ-Olfm1 and miR-330-5p.Western blotting showed that the addition of Aβ42 significantly increased the expression of AMPK and FOXO3a in the neuronal cells(P<0.01).And silencing circ-Olfm1 led to decreased expression of AMPK and FOXO3a in neuronal cells+Aβ42(P<0.01).ELISA revealed that knockout of FOXO3a significantly increased the levels of inflammatory factors IL-6,IL-1β,and TNF-α(P<0.01).Transmission electron microscopy displayed that knocking FOXO3a out significantly aggravated mitochondrial damage(P<0.01).Conclusion circ-Olfm1 is up-regulated in the brain tissue and neurons+Aβ42 of AD rats,and the mechanism of cognitive impairment in AD rats may be through its regulating FOXO3a protein.

Objective To map the genome-wide distribution profile of histone H3K27me3 modification in diffuse gastric cancer tissues,identify target genes regulated by H3K27me3,and primarily explore the potential mechanism of its modification reprogramming in the occurrence and development of the tumor.Methods Normal gastric mucosal tissues and diffuse gastric cancer tissues were harvested from the patients who underwent examinations or treatments in the departments of gastroenterology and gastrointestinal surgery of our medical center between 2021 and 2023.There were 14 patients in the normal group(6 males and 8 females,average age of 46 years)and 14 patients in the gastric cancer group(8 males and 6 females,average age of 63 years).Cleavage under target and tagmentation(CUT&Tag)technology was employed to capture genomic regions modified by H3K27me3,and analyze the reprogramming characteristics of these modifications.RNA sequencing data,data from high-throughput chromosome conformation capture(Hi-C)technology,and publicly available single-cell data were integrated to investigate the target genes regulated by the reprogramming of H3K27me3 modifications in diffuse gastric cancer cells.Results The quality of the CUT&Tag and RNA sequencing data met the standards required for subsequent analysis.Histone H3K27me3 modifications in normal gastric mucosa and diffuse gastric cancer tissues were primarily distributed in distal intergenic regions and intronic regions.In gastric cancer tissues,compared to normal tissues,there was significant reprogramming of H3K27me3 modifications,characterized by a marked reduction in overall H3K27me3 signal intensity.The loss of 2 912 H3K27me3 signal peaks might lead to the up-regulation of 822 tumor-associated genes.Among them,56 genes displayed the most significant up-regulation(fold change in signal intensity≥2,P<0.05),with notable enrichment in the mammalian target of rapamycin complex 1(mTORC1)signaling pathway.Specifically,the methionine transporter SLC7A5 and the cystine transporter SLC7A11 were found to have the highest expression levels in gastric cancer tissues.Single-cell data revealed that the abnormal overexpression of SLC7A11 in diffuse gastric cancer was primarily observed in tumor epithelial cells.Further validation using public data and immunohistochemical experiments confirmed the elevated expression of SLC7A11 in diffuse gastric cancer,which is associated with poor prognosis in gastric cancer patients.Conclusion The reprogramming of histone H3K27me3 modification is an important epigenetic characteristic in diffuse gastric cancer.Loss of H3K27me3 signal peaks may up-regulate the expression of SLC7A11 in diffuse gastric cancer cells,and thereby promote tumor progression.

Objective To investigate the underlying mechanism of abnormal specification of spermatogonial stem cells(SSCs)in male mice following Rb1 conditional knockout in mitotic-arrested prospermatogonia.Methods ① R language was used to analyze the single-cell RNA sequencing(scRNA-seq)data of prospermatogonia derived from postnatal day 0.5(P0.5)male mice through the gene expression omnibus(GEO)public database(accession number:GSE124904).② Mitoti-arrested prospermatogonia Rb1 conditional knockout(cKO)mice as well as Rb1 cKO mice with Id4-gfp transgene were generated using Vasa-Cre mice crossed with Rb1flox/flox or Id4-gfpTg;Rb1flox/flox mice.PCR was employed to detect the deletion of Rb1 in order to distinguish the control and cKO male mice.The testes of male mice(n=3～8)within a few days after birth were collected.After that,flow cytometry was applied to divide the ID4-GFP cells into 3 communities based on the GFP fluorescence intensity,and then detect the number of cells and cell cycle in each community.③ Germ cell proliferation(Ki67 positive,Ki67+),SSCs specification(FOXO1 nuclear transition),and germ cell differentiation(STRA8+)were detected with immunofluorescence staining.④ TUNEL staining was utilized to detect cell apoptosis.Results ① The results of scRNA-seq showed that in the two set clusters of prospermatogonia,the prospermatogonia that further specifies to generate SSCs had enriched genes that are associated with cell proliferation.② Germ cell proliferation assay indicated that the average ratio of Ki67+germ cells in the testicular cross-section of the cKO mice was significantly higher than that of the control mice at P2.5[(46.10±6.21)%vs(11.22±3.27)%,P<0.01].③ Flow cytometry revealed that,among the brightest community of ID4-GFP cells,the percentage of the cells at S phase was obviously higher in the testicular cells derived from the cKO mice when compared to the control mice at P2.5[(12.05±1.22)%vs(5.05±1.46)%,P<0.05].④ TUNEL staining displayed that cell apoptosis was detected in the testicular cross-section of cKO mice rather than that of the control mice.⑤ The results of SSCs specification exploration showed that statistical difference was observed in the percentage of cytoplasmic FOXO1 in the testicular cross-section between the control and cKO mice[(20.57±2.15)%vs(45.08±2.45)%,P<0.01].Conclusion Rb1 knockout in mitotic-arrested prospermatogonia disrupts their postnatal cell cycle re-enter and induces cell apoptosis,which further results in abnormal SSC specification.

Objective To construct a mammography image classification assistant system suitable for Chinese population,and explore the potential of artificial intelligence technology to assist early screening of breast cancer in China.Methods Curated breast imaging subset of digital database for screening mammography(CBIS-DDSM),Mammographic image analysis society database(MIAS)and other international open datasets were used to conduct model training respectively in order to reproduce the mainstream in-depth learning methods in the current literature.The model was also tested on the Chinese breast mammography database(CBMD)provided by Huajiao Technology Co.,Ltd,and the performance was compared.Aiming at the problem that the Chinese population data are not ideal in the performance test of the open dataset training model,an optimization strategy based on the sliding window adjustment mechanism was implemented in combination with the characteristics of Chinese population data.Then a two-stage migration learning method was designed to improve the overall performance of the model,and then development of our system was carried out.Results With the sliding window adjustment mechanism and the CBMD training model after two-stage transfer learning,the accuracy of our developed system was improved from 0.50 of the open datasets to 0.80,precision from 0.54 to 0.82,sensitivity from 0.52 to 0.80,F1 value from 0.52 to 0.80,and AUC value from 0.51 to 0.89 based on the Chinese population dataset as the test set.Conclusion Through the introduction of sliding window adjustment mechanism and two-stage migration learning strategy,the performance of the breast molybdenum target image classification model has been significantly improved in the Chinese population dataset,and our system primarily achieves the purpose of assisting the classification of breast molybdenum target images for the Chinese population.