ObjectiveTo study the effect of Taikong Yangxin Pills on the metabolism of simulated weightless rats based on metabolomics and discuss the metabolism mechanism. MethodsIn the simulated space capsule environment on the ground， the rat model of simulated weightlessness was established by the tail suspension method. Rats were randomly grouped as follows： out-of-capsule control， in-capsule control， model， and high （3.0 g·kg^-1） and low （1.5 g·kg^-1） doses of Taikong Yangxin Pills， and they were administrated with corresponding drugs by gavage for 28 days. The serum levels of endogenous metabolites in rats were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF/MS）. The obtained data were processed by principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） to screen for differential metabolites and potential biomarkers. MetaboAnalyst 5.0 was used for pathway enrichment analysis to explain the metabolic regulation mechanism of the drug. ResultsCompared with the out-of-capsule control group， the in-capsule control group showed elevated levels of thirteen metabolites， including 14-hydroxyhexadecanoic acid， linoleic acid， and α-linolenic acid （P<0.05）， which suggested that the space capsule environment mainly affected the metabolism of α-linolenic acid and linoleic acid in the rats. Compared with the in-capsule control group， the model group showed lowered levels of fourteen metabolites， including 4-imidazolone-5-propionic acid， isocitric acid/citric acid， and L-tyrosine （P<0.05）， which were recovered after the treatment with Taikong Yangxin pills （P<0.05）. The pathway enrichment analysis revealed that weightlessness induced by tail suspension and drug intervention mainly involved the phenylalanine， tyrosine， and tryptophan biosynthesis， tyrosine metabolism， histidine metabolism， and citric acid cycle. ConclusionThe simulated space capsule environment and simulated weightlessness induced by tail suspension can both affect the metabolism level of rats. Taikong Yangxin pills can ameliorate the metabolic abnormality in the rat model of weightlessness by regulating various amino acids and energy metabolism-related pathways.

Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.

A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in Fgfr1 knockout (Fgfr1-KO ^+/- ) diabetic mice. Meanwhile, testicular-specific overexpression of Tak1 abolished the protective effect of FGF1^mut on diabetic mouse testis. Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.

This article procides a review of the current research status of the application of traditional Chinese medicine in manned spaceflight:(1)Current status of theoretical research on traditional Chinese medicine in aerospace;(2)The research and application status of traditional Chinese medicine diagnostic technology in aerospace;(3)Current status of traditional Chinese medicine intervention research on aerospace medicine issues;(4)The current status of traditional Chinese medicine non pharmacological intervention research on aerospace medicine issues;(5)The application status of traditional Chinese medicine in China's manned space missions.Looking ahead to the future,we aim to build a discipline of traditional Chinese medicine in space from the aspects of theoretical establishment,technological method innovation,and product development for manned lunar landing and deep space exploration missionss.

Objective Observe the impact of Qang Gu Kang Wei extraction(KW)on skeletal muscle atrophy in simulated weightlessness rats by regulating endoplasmic reticulum stress and mitochondrial fusion.Methods SD rats were randomy divided the control group(Control),the simulated weightlessness group(TS),and the KW group(TS+KW).Rats were treated with KW with or without tail suspension(TS)for 28 days,and the cross-sectional areas of the gastrocnemius muscle were compared with a control group.The expression levels of endoplasmic reticulum stress(ERS)and key proteins involved in mitochondrial fusion were also analyzed.Results KW treatment reduced the loss of muscle cross-sectional area caused by TS.TS increased the protein expression of glucose-regulated Protein 78(GRP78)and components of the ERS signaling pathways,while KW treatment reduced this increase.TS also inhibited the expression of mitofusin 2(MFN2),which was increased by KW treatment.Additionally,KW treatment promoted the interaction between GRP78 and the endoplasmic reticulum protein sigma-1 receptor(Sig-1R).Conclusion KW may attenuate muscle atrophy caused by simulated weightlessness by regulating ERS and mitochondrial fusion fusion.

Objective Hypobaric chamber and simulated weightless bed are essential methods for aerospace medical research,and conducting state assessment of volunteers before and after hypobaric chamber and simulated weightless bed tests is an essential guideline for aerospace implementation medicine.To further improve the efficiency of human condition assessment,in addition to the conventional biochemical and physiological indicators,the human oral exhaled gas can be used for condition assessment,and the olfactometry acquisition equipment and analysis software can collect and detect most volatile gases to complete the human oral exhaled gas data acquisition.Conducting comparative analysis of olfactory mapping data from different populations may be a means to assess the status of the body.Methods The olfactometry acquisition equipment was used to collect the oral exhaled breath olfactometry profiles of the general population,hypobaric cabin volunteers,and ambulatory volunteers.The olfactometry analysis software was used to calculate the 12 eigenvalues of the olfactometry profiles and the t-SNE downscaling,and the radar plots were used to analyze the olfactometry profiles of the general population,low-pressure cabin volunteers,and ambulatory volunteers respectively.A comparative analysis of different populations was conducted.Results(1)The t-SNE mapping data of the general population and the ambulatory volunteers were almost indistinguishable;(2)the t-SNE mapping data of the hypobaric cabin volunteers and the general population had a slight overlap,but the distinguishability of the vast majority of the t-SNE mapping data was obvious;(3)the t-SNE mapping data of the hypobaric cabin volunteers and the ambulatory volunteers were distinguishable with no overlap,and the ambulatory t SNE data are highly aggregated,and the distribution of t-SNE data in low-pressure cabin is more discrete;(4)there are 2-3 sensors with large eigenvalues and a large range of variation for both low-pressure cabin volunteers and recumbent volunteers after training activities,and the common sensor with a large range of variation is S6.Conclusion Olfactory diagnostic analysis mapping may be a means to assess the health status of the body and may be useful for spaceflight health status assessment in the future.The analysis and application of flight health state assessment can be a reference in the future.

Objective To explore the risk factors for suicidal ideation among the relatives and friends of suicide victims through psychological support hotline.Methods Calls from the relatives and friends of suicide victims to the Beijing psychological support hotline between 2009 and 2023 were included.Their current suicidal ideation was assessed by asking whether they had suicidal thoughts in the past two weeks.Demographic information of the callers was collected and the severity of their depression was assessed using the depression diagnostic screening scale.Interviews were conducted to evaluate distress,sense of hope,history of suicide attempts,and suicide risk factors.Logistic regression analysis was used to explore the risk factors for suicidal ideation among callers.Results A total of 360 cases were included in this study.There were 50.3%(181 cases)of the callers reporting suicidal ideation within 2 weeks before the call.Years of education(OR=0.86,95%CI:0.79-0.94)and high levels of hope(OR=0.19,95%CI:0.11-0.32)were protective factors against suicidal ideation in callers.History of suicide attempts(OR=2.01,95%CI:1.20-3.36),high levels of distress(OR=3.28,95%CI:1.92-5.61),and high levels of depression(OR=1.73,95%CI:1.05-2.84)were independent risk factors for suicidal ideation in callers.Conclusions History of suicide attempts,high levels of distress and high levels of depression among the relatives and friends of suicide victims calling the psychological support hotline are risk factors for their own suicidal ideation.

Objective:To explore the role of arginine metabolism in the inflammatory response to influenza A virus (FluA) infection.Methods:Eighteen-month-old mice were infected with FluA via nasal drip, with samples collected on the 6th day post-infection. The concentration of cytokines was determined by the Luminex multifactor assay, while the metabolites in bronchoalveolar lavage fluid (BALF) were analyzed using targeted metabolomic method. Correlation analysis was employed to examine the correlation between cytokines and metabolites. Macrophages were infected with FluA at a multiplicity of infection (MOI) of 1 and cultured with different concentrations of arginine for 24 h. The mRNA and protein expression levels of interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α) and IL-10 were detected by real time fluorescence quantitative RT-PCR (qRT-PCR) and Cytometric Bead Array (CBA).Results:In comparison to the control group, the levels of surfactant protein D (SP-D), TNF-α, monocyte chemotactic protein-1 (MCP-1), IL-1α, IL-6, IL-10, recombinant S100 calcium binding protein (S100) A9, interferon inducible protein 10 (IP-10), macrophage inflammatory protein-1α (MIP-1α), matrix metalloprotein-9 (MMP-9), and Complement Factor D in BALF of FluA infection exhibited a significant elevation. The concentrations of arginine, aspartate, citrulline, glutamic acid, ornithine, proline, creatine, and sarcosine in arginine metabolism were up-regulated, which was correlated with most of elevated cytokine levels. The supplementation of arginine after FluA infection significantly decreased the levels of IL-1β, IL-6, and TNF-α, but increased the level of IL-10 in macrophages.Conclusions:Arginine reduces the inflammatory response induced by FluA infection in macrophages, suggesting that it may be a potential intervention target for severe pulmonary inflammation following FluA infection.

Objective To develop a Traditional Chinese Medicine(TCM)syndrome diagnosis scale suitable for evaluating the overall health status of participants in long-term simulated weightlessness experiments,and preliminarily evaluate its reliability and validity.Methods Based on the understanding of the pathogenesis of TCM in different stages of long-term manned spaceflight,a scale was developed through literature research and expert consultation.Test-retest reliability and internal consistency coefficient were used to test the reliability of the scale.Item analysis and factor principal component analysis were used to evaluate the validity of the scale,and a rotating component matrix was used to analyze the correlation between each item and dimension using 36 volunteers in a 90 days head down bed rest experiment as the research subjects.Results The scale contains eight dimensions and 57 items.The reliability analysis showed that the correlation coefficient of the total score of the scale for the first and second tests of 30 participants was 0.889,indicating high stability of the scale.The Cronbach coefficient of the scale was 0.934,indicating very good internal consistency.The split half reliability after correction was 0.858,indicating a high reliability of the scale.The validity analysis showed that the difference between the high score group and the low score one for each of the 57 items was statistically significant(P<0.01),and the Pearson correlation coefficient between each item and the total score of the scale was greater than 0.4(P<0.001).The cumulative contribution rate of 8 common factors extracted using principal component factor analysis was 55.293%,and the results of rotating component matrix analysis,after applying TCM theory and expert feedback,had a coincidence of up to 87.5%with the initial 8 dimensions,indicating good structural validity of the scale.Conclusion The scale has good reliability and validity,and can diagnose TCM syndromes.It is suitable for long-term simulated weightlessness experiment and provides an objective and quantitative new method for evaluating the subjective feelings of participants.

Objective This study investigated whether gut microbiota and its metabolites are altered in myasthenia gravis(MG)patients.Methods We collected fresh stool specimens from MG patients and healthy controls.16S rRNA gene sequencing and gas chromatography-mass spectrometry were used to measure abundance of gut microbiota and metabolite levels in two groups,respectively.Clinical data of the subjects were also collected including quantitative MG score(QMGS),MG-activities of daily living(MG-ADL),MG-specific quality-of-life 15(MG-QOL15),manual muscle testing(MMT),and the acetylcholine receptor antibody(AchR-Ab)titers.The correlation between the differential microbiota and the clinical characteristics was investigated.Results A total of 50 MG patients and 15 healthy controls were recruited.Simpson's index was significantly higher in the MG group(0.936±0.041)than in the control group(0.888±0.123).Alpha diversity was significantly decreased in the MG group(t=2.349,P=0.022).There was a significant difference in microbial phenotype between the two groups(R=0.966,P=0.001,Adonis).The results of LEfSe showed that the abundance of Esherichia-Shigella,Succinivibrio,Fusobacterium,and Ruminococcus-gnavus-group were up-regulated while the abundance of Lachnospira,Roseburia,Desulfovibrio,and Coprococcus were down-regulated.The results showed that the metabolites of the MG group were significantly different from those of the control group.There were 28 metabolites up-regulated and 71 metabolites down-regulated in the MG patient group.Kyoto Encyclopedia of Genes and Genomes analyses demonstrated that the majority of metabolic pathways in which differential metabolites were involved were related to amino acid metabolism and nucleotide metabolism.61.2% (30/49)of bacterial amplicon sequence variant(ASV)were significantly associated with multiple metabolites(P<0.001).The relative abundance of Lachnospiraceae in the group with MG was negatively correlated with the QMGS(r=-0.496,P<0.001),MG-ADL(r=-0.542,P<0.001),MG-QOL15(r=-0.464,P=0.007),and the AchR-Ab(r=-0.315,P=0.026).The relative abundance of Lachnospiraceae in the group with MG was positively correlated with the MMT(r=0.374,P=0.008).Conclusion The intestinal flora of MG patients is down-regulated in the abundance of beneficial bacteria and up-regulated in the abundances of harmful bacteria.Disturbance of metabolites are also present in MG patients.Regulating gut microbiota in MG patients may be a new target for treating the disease.