Microgravity in space will lead to the decline of astronauts'motor sensation,which will affect the ability of balance maintenance and posture control.Which limits the ability of astronauts to quickly get out of danger in case of extravehicular activities or landing emergencies,and seriously affects the completion of space missions and endangers the safety of astronauts.The current weightlessness countermeasure based on exercise can effectively alleviate the problems of skeletal muscle and cardiovascular system caused by weightlessness to a certain extent,but it cannot effectively prevent the motor sensory dysfunction after space flight.Therefore,new weightlessness countermeasures of special physical conditioning are needed to attenuate the decline of human balance control ability after long-term space flight.By reviewing the previous research results of space flight and simulated weightlessness experiments,this paper systematically analyzes the influencing factors of human body balance control,compares the balance control promotion schemes of special physical conditioning in the field of sports,and puts forward the potential protection strategies for weightlessness environment based on the integration of sports and medicine.The feedback regulation of muscle tension,tactile and proprioceptive play an important role in human posture balance and motion control.The unloading of human gravity load in space weightlessness environment will greatly reduce the input-output feedback regulation activity of the above senses which may lead to balance dysfunction.The post-flight balance control dysfunction may be improved by special physical conditioning,such as loading of z-axial load,enhancement of tactile feedback and proprioceptive response based on unstable mechanical stress stimulation during spaceflight.

Amino-containing compounds,including amino acids,aliphatic amines,aromatic amines,small peptides and catecholamines,are involved in various biological processes and play vital roles in multiple meta-bolic pathways.Previous studies indicated that some amino-containing metabolites are significant diagnostic and prognostic biomarkers of gastric cancer.However,the discovery of precise biomarkers for the preoperative diagnosis of gastric cancer is still in an urgent need.Herein,we established a polarity-regulated derivatization method coupled with liquid chromatography-mass spectrometry(LC-MS)for amino-containing metabolites profiling in the serum samples of patients with gastric cancer and healthy controls,based on our newly designed and synthesized derivatization reagent(S)-3-(1-(diisopropox-yphosphoryl)pyrrolidine-2-carboxamido)-N-hydroxysuccinimidyl ester(3-DP-NHS).Enhanced separa-tion efficiency and detection sensitivity for amino-containing metabolites were achieved after derivatization.This method exhibited good linearity,recovery,intra-and inter-day precision and accu-racy.Only 5 μL serum is needed for untargeted analysis,enabling 202 amino-containing metabolites to be detected.Statistical analysis revealed altered amino acid metabolisms in patients with gastric cancer.Furthermore,ultra high performance liquid chromatography coupled with mass spectrometry(UHPLC-MS/MS)analysis quantification revealed increased serum levels of tryptamine and decreased concen-trations of arginine and tryptophan in patients with gastric cancer.Receiver operating characteristic(ROC)curves indicated that an increased tryptamine/tryptophan ratio could serve as a potential biomarker for gastric cancer diagnosis.This study demostrated the possibility of using serum amino acid biomarkers for gastric cancer diagnosis,providing new avenues for the treatment of gastric cancer.

Objective:To explore the relevance of a new comprehensive respiratory mechanics parameter, elastic power, to the 28-day prognosis of ARDS patients.Methods:Patients with ARDS hospitalized for at least 48 h with invasive mechanical ventilation in five intensive care units in three local hospitals in Lianyungang City from June 2018 to June 2022 were included in the study. Their baseline data and respiratory mechanics parameters were collected. Elastic power, mechanical power, driving pressure and lung compliance are calculated according to the corresponding formulae. The prognostic risk factors of ARDS patients were analysed using COX multi-factor regression, and the predictive value of EP/Cst on the 28-day prognosis of ARDS patients was evaluated based on ROC curve analysis and Kaplan-Meier survival curve.Results:There was no significantly difference in tidal volume and PEEP settings between the patients in the ARDS survivor and death groups ( P> 0.05). However, the differences in respiratory rate, plateau pressure, driving pressure, lung compliance, mechanical work, elastic work, EP/cst and MP/cst between the two groups were significantly different (all P< 0.01). Multifactorial COX regression analysis showed that EP/cst ( HR=1.211, 95% CI:1.091-1.323) and RR ( HR=1.209, 95% CI:1.046-1.339) were strongly associated with a more severe degree of illness and a worse prognosis in ARDS. And the cumulative survival rate at 28 d was significantly lower in the high Cst-EP group than in the low Cst-EP group (50.00% vs. 82.40%, P < 0.01). Conclusions:The new respiratory mechanics parameters EP and EP/Cst can assess the severity of ARDS with a good predictive effect on patient prognosis at 28 days.

Trace amines(TAs)are metabolically related to catecholamine and associated with cancer and neuro-logical disorders.Comprehensive measurement of TAs is essential for understanding pathological pro-cesses and providing proper drug intervention.However,the trace amounts and chemical instability of TAs challenge quantification.Here,diisopropyl phosphite coupled with chip two-dimensional(2D)liquid chromatography tandem triple-quadrupole mass spectrometry(LC-QQQ/MS)was developed to simul-taneously determine TAs and associated metabolites.The results showed that the sensitivities of TAs increased up to 5520 times compared with those using nonderivatized LC-QQQ/MS.This sensitive method was utilized to investigate their alterations in hepatoma cells after treatment with sorafenib.The significantly altered TAs and associated metabolites suggested that phenylalanine and tyrosine metabolic pathways were related to sorafenib treatment in Hep3B cells.This sensitive method has great potential to elucidate the mechanism and diagnose diseases considering that an increasing number of physiological functions of TAs have been discovered in recent decades.

Objective:To investigate the protective effects and related mechanisms of Astragaloside Ⅳ(ASⅣ)alleviating Angiotensin II-induced cardiomyocyte hypertrophy.Methods:H9c2 cardiomyocytes were divided into six groups: normal control group, ASⅣ group(ASⅣ 100 μmol/L), AngⅡ group(AngⅡ 1 μmol/L), and three ASⅣ dose experiments(AngⅡ 1 μmol/L + ASⅣ 25 μmol/l group, AngⅡ 1 μmol/L+ ASⅣ 50 μmol/l group, AngⅡ1 μmol/L+ ASⅣ 100 μmol/L group), and simultaneously cultured for 24 hours.Cardiomyocyte viability was assessed by CCK8 assay, and surface area of culturedcardiomyocytes in each group was assessed by immunofluorescence assay.Atrial natriuretic peptide(ANP)mRNA expression was assessed by fluorescence real-time quantitative RT-PCR.And LC3 protein expression, an autophagy related protein, was assessed by Western blotting as well as immunofluorescence.Results:(1)AngⅡ decreased cardiomyocyte H9c2 viability in a dose-dependent manner( P<0.05). ASⅣ could inhibit the decrease of cardiomyocyte H9c2 viability in response to AngⅡ in a dose-dependent manner( P<0.05). (2)H9c2 cardiomyocytes induced by AngⅡ showed a significantly larger cell area and significantly higher ANP mRNA and ANP protein expression compared with controls.Different concentrations of ASⅣ intervention could reverse the increase of cardiomyocyte H9c2 area induced by AngⅡ and also decreased the expression of ANP protein induced by AngⅡ in a dose-dependent manner(all P<0.05). (3)Compared with the control group, the autophagy level and the expression of autophagy marker LC3II/I of H9c2 cardiomyocytes induced by AngⅡ were significantly increased(all P<0.05). ASⅣ could inhibit AngⅡ-activated autophagy, and the difference was statistically significant( P<0.05). ASⅣ inhibited the expression of LC3II/I in H9c2 cardiomyocytes stimulated by AngⅡ, and the difference was statistically significant( P<0.05). Conclusions:ASⅣ inhibits AngⅡ-induced cardiac hypertrophy by inhibiting autophagy of cardiomyocytes.

Objective:To investigate whether cachexia affects the treatment effect of immune checkpoint inhibitors for non-small cell lung cancer (NSCLC).Methods:The prognosis of 62 patients with advanced NSCLC who received anti-programmed cell death-1 (PD-1) in Henan Provincial People′s Hospital from 2019 to 2021 were retrospectively analyzed. The cachexia was evaluated before and after the second course of immunotherapy. Kaplan-Meier and Log rank methods were used for survival analysis, Cox regression model was used for multivariate analysis, and Spearman′s correlation analysis was used for correlation analysis.Results:After the second course of immunotherapy, psoas major muscle area (PMMA) values of the cachexia group and the control group were (14.10±4.09) and (11.66±3.22) cm 2 respectively, with statistics significance ( P=0.001). The level of Prealbumin and body weight were correlated with cachexia ( P<0.05). The 6-month and 1-year survival rates of 62 cases in the whole group were 58.6% and 42.5%, respectively. The progression-free survival (PFS) in the control group (7.6 months) was higher than that in the cachexia group (3.8 months, P=0.006). The PFS in patients with high expression of PD-L1 (7.1 months) was longer than that of patients with low expression (3.8 months, P=0.009). The overall survival (OS) in the cachexia group (6.3 months) was lower than that in the control group (18.2 months, P=0.006). The OS in patients with high expression of PD-L1 (14.5 months) was longer than that of patients with low expression (1 months, P=0.038). The level of Prealbumin, the level of PD-L1 expression and the change rate of PMMA were related to the OS of the patients ( P<0.05). The level of Prealbumin and the change rate of PMMA were the independent influencing factors of the OS ( P<0.05). The PMMA and the level of Prealbumin were negatively correlated ( r=-0.003 8, P<0.05). Conclusion:Cachexia has a negative impact on the outcomes of patients who received anti-PD-1 immune checkpoint inhibitor therapy.

Objective:To investigate whether cachexia affects the treatment effect of immune checkpoint inhibitors for non-small cell lung cancer (NSCLC).Methods:The prognosis of 62 patients with advanced NSCLC who received anti-programmed cell death-1 (PD-1) in Henan Provincial People′s Hospital from 2019 to 2021 were retrospectively analyzed. The cachexia was evaluated before and after the second course of immunotherapy. Kaplan-Meier and Log rank methods were used for survival analysis, Cox regression model was used for multivariate analysis, and Spearman′s correlation analysis was used for correlation analysis.Results:After the second course of immunotherapy, psoas major muscle area (PMMA) values of the cachexia group and the control group were (14.10±4.09) and (11.66±3.22) cm 2 respectively, with statistics significance ( P=0.001). The level of Prealbumin and body weight were correlated with cachexia ( P<0.05). The 6-month and 1-year survival rates of 62 cases in the whole group were 58.6% and 42.5%, respectively. The progression-free survival (PFS) in the control group (7.6 months) was higher than that in the cachexia group (3.8 months, P=0.006). The PFS in patients with high expression of PD-L1 (7.1 months) was longer than that of patients with low expression (3.8 months, P=0.009). The overall survival (OS) in the cachexia group (6.3 months) was lower than that in the control group (18.2 months, P=0.006). The OS in patients with high expression of PD-L1 (14.5 months) was longer than that of patients with low expression (1 months, P=0.038). The level of Prealbumin, the level of PD-L1 expression and the change rate of PMMA were related to the OS of the patients ( P<0.05). The level of Prealbumin and the change rate of PMMA were the independent influencing factors of the OS ( P<0.05). The PMMA and the level of Prealbumin were negatively correlated ( r=-0.003 8, P<0.05). Conclusion:Cachexia has a negative impact on the outcomes of patients who received anti-PD-1 immune checkpoint inhibitor therapy.

Objective:To investigate the mechanism of cathepsin G(CatG) in improving the treatment efficacy of T cells in gliomas.Methods:(1) Clinical data of 397 glioma patients in the glioma database were collected, Kaplan-Meier method was used to perform survival analysis, and the correlation between CTSG and β2-microglobulin ( β2M) mRNA expressions in glioma tissues was analyzed. (2) Glioma stem cell (GSC) 387 and GSC3565 were isolated from glioblastoma and differentiated into differentiated glioma cell (DGC) 387 and DGC3565, respectively; GSC387 was divided into CatG group and CatG inhibitor group, and cells in the CatG group and CatG inhibitor group were cultured with 0.1 μg/μL recombinant human leukocyte antigen (HLA)-A*02:01 and HLA-B*15:01 combined with 4 ng/μL CatG or 10 mol/L CatG inhibitor for 10 min, respectively; the expressions of HLA-A*02:01 and HLA-B*15:01 were detected by Thomas bright blue staining, and the protein expressions of major histocompatibility complex (MHC)-I and MHC-DR were detected by Western blotting. (3) GSC387, GSC3565, DGC387, and DGC3565 were divided into 4 groups, including CatG group, CatG inhibitory group, blank antibody group 1 and blank antibody group 2, respectively; 4 ng/μL CatG, 10 μmol/L CatG inhibitor, blank antibody 1 and blank antibody 2 were added into the cells from the 4 groups for 24 h, and the expression of HLA-ABC was detected by flow cytometry. (4) GSC387, GSC3565, DGC387, and DGC3565 were divided into CatG group and CatG inhibitory group, respectively; luciferase assay was used to detect the influence of CatG in the killing effects of T cells and natural killer cells. Results:(1) The survival rate in patients from CTSG mRNA high expression group was significantly higher than that in patients from CTSG mRNA low expression group, and the survival rate in patients from β2M mRNA low expression group was statistically higher than that in patients from β2M mRNA high expression group ( P<0.05); a negative correlation between CTSG mRNA and β2M mRNA expressions was noted in glioma tissues ( r=-9.160, P=0.000). (2) Thomas bright blue staining showed that the expressions of HLA-A*02:01 and HLA-B*15:01 obviously increased in the CatG group as compared with those in the CatG inhibitor group; Western blotting showed that as compared with the CatG inhibitor group, the CatG group had increased MHC-I expression, and decreased expressions of α and β chains of MHC-DR. (3) Flow cytometry showed that the HLA-ABC expressions in GSC387 and GSC3565 of the CatG group were statistically higher than those in the CatG inhibitor group ( P<0.05). (4) Luciferase assay showed that, as compared with the CatG inhibitor group, the CatG group had statistically higher proportion of T cells killing GSCs ( P<0.05). Conclusion:CatG can improve the immunotherapy efficacy in GSCs, mainly by increasing the MHC-I expression on the cell surface.