Objective:To investigate the effects of 10° head up tilt bed rest (HUT) on human cardiac function via 3D speckle tracking echocardiography (3D-STE), and to study the difference in cardiac function under the submaximal exercise load between the horizontal position and 10° HUBR.Methods:Thirty young healthy volunteers were recruited as the subjects, who were randomly divided into an 10° HUT exercise group and horizontal exercise group with 15 subjects in each. Subjects in both groups were asked to ride the bicycle ergometer in the 10° HUBR position and supine position respectively. The load started with 50 W and was increased by 25 W every 3 min until it reached the maximum of 125 W. Before the exercise (resting state), 1 min after the load was increased each time, and 3 min after exercise (recovery period), the following indices were collected: ①basic cardiac function indices: heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), ②conventional cardiac ultrasound indices: left ventricular ejection fraction (LVEF), stroke volume (SV) and cardiac output (CO), ③left ventricular strain indices: global longitudinal strain (GLS), global circumferential strain (GCS), and global area strain (GAS) measured by 3D-SET. The changes of these indices in the 2 groups of subjects under different exercise loads were observed.Results:The differences in the major effect of the basic heart indices (HR, SBP and DBP), conventional cardiac ultrasound indices (LVEF, SV and CO) and left ventricular strain indices (GLS, GCS and GAS) in response to the exercise load were statistically significant ( F=194.90, 113.66, 17.19, P=0.017, 0.018, 0.001). With the increase of the exercise load, the basic heart indices and conventional cardiac ultrasound indices kept rising, the left ventricular strain indices reached the minimum under a moderate exercise load (75 W), HR, SBP and CO were higher than those of the resting state ( P<0.05 or 0.01). Both LVEF under exercise loads of 75, 100, 125 W and during recovery, and SV under exercise loads of 100, 125 W and during recovery were significantly higher than those of the resting state ( P<0.05 or 0.01), while GLS and GCS under exercise loads of 50, 75, 125 W ( P<0.05 or 0.01), and GAS under exercise loads of 50, 75 W ( P<0.01) were significantly lower. There were statistically significant differences not only in GCS across the groups ( F=4.60, P=0.026) but also in DBP due to the interactions between the grouping and exercise loads ( F=3.13, P=0.031). DBP was higher than that of the resting state when the exercise load was 125 W in both groups. Conclusions:During submaximal exercise, myocardial contractility shows sustained enhancement with the increase of the exercise load. The results of GLS, GCS and GAS indicate that myocardial strain reaches its lowest value under a moderate exercise load, suggesting that moderate exercise can be used to evaluate cardiac function via 3D-SET. Under a simulated lunar gravity of 10° HUT, there is less deformation in the short axis direction of the myocardium, indicating that GCS can be used as a sensitive indicator to detect changes in cardiac function under different gravities.

Objective:To investigate the effects of 10° head up tilt bed rest (HUT) on human cardiac function via 3D speckle tracking echocardiography (3D-STE), and to study the difference in cardiac function under the submaximal exercise load between the horizontal position and 10° HUBR.Methods:Thirty young healthy volunteers were recruited as the subjects, who were randomly divided into an 10° HUT exercise group and horizontal exercise group with 15 subjects in each. Subjects in both groups were asked to ride the bicycle ergometer in the 10° HUBR position and supine position respectively. The load started with 50 W and was increased by 25 W every 3 min until it reached the maximum of 125 W. Before the exercise (resting state), 1 min after the load was increased each time, and 3 min after exercise (recovery period), the following indices were collected: ①basic cardiac function indices: heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), ②conventional cardiac ultrasound indices: left ventricular ejection fraction (LVEF), stroke volume (SV) and cardiac output (CO), ③left ventricular strain indices: global longitudinal strain (GLS), global circumferential strain (GCS), and global area strain (GAS) measured by 3D-SET. The changes of these indices in the 2 groups of subjects under different exercise loads were observed.Results:The differences in the major effect of the basic heart indices (HR, SBP and DBP), conventional cardiac ultrasound indices (LVEF, SV and CO) and left ventricular strain indices (GLS, GCS and GAS) in response to the exercise load were statistically significant ( F=194.90, 113.66, 17.19, P=0.017, 0.018, 0.001). With the increase of the exercise load, the basic heart indices and conventional cardiac ultrasound indices kept rising, the left ventricular strain indices reached the minimum under a moderate exercise load (75 W), HR, SBP and CO were higher than those of the resting state ( P<0.05 or 0.01). Both LVEF under exercise loads of 75, 100, 125 W and during recovery, and SV under exercise loads of 100, 125 W and during recovery were significantly higher than those of the resting state ( P<0.05 or 0.01), while GLS and GCS under exercise loads of 50, 75, 125 W ( P<0.05 or 0.01), and GAS under exercise loads of 50, 75 W ( P<0.01) were significantly lower. There were statistically significant differences not only in GCS across the groups ( F=4.60, P=0.026) but also in DBP due to the interactions between the grouping and exercise loads ( F=3.13, P=0.031). DBP was higher than that of the resting state when the exercise load was 125 W in both groups. Conclusions:During submaximal exercise, myocardial contractility shows sustained enhancement with the increase of the exercise load. The results of GLS, GCS and GAS indicate that myocardial strain reaches its lowest value under a moderate exercise load, suggesting that moderate exercise can be used to evaluate cardiac function via 3D-SET. Under a simulated lunar gravity of 10° HUT, there is less deformation in the short axis direction of the myocardium, indicating that GCS can be used as a sensitive indicator to detect changes in cardiac function under different gravities.

Objective:To provide references for achieving long time continuous monitoring of cardiac functional changes of astronauts in spaceflight activities through continuously noninvasive assessment of left ventricular systolic function under exercise load by wearable cardiac sounds and ECG signals synchronization monitoring technology.Methods:Eleven healthy male youths were recruited for the study, and they did incremental load exercise on the recumbent power bicycle, starting at 50 W, increasing by 25 W every 3 minutes, until the maximum of 125 W reached. The subjects′ cardiac sounds and ECG signals at rest, 1 min after each level of load during exercise and 3 min after the end of exercise were selected; the transthoracic cardiac ultrasound examination of subjects was performed before and 5 min after exercise. The correlation between the cardiac sounds and ECG signals and left ventricular ejection fraction (LVEF) was analyzed, and a regression model was established to predict LVEF during exercise.Results:There were significant differences in heart rate, LVEF, electro-mechanical activation time (EMAT) and left ventricular ejection time (LVET) of subjects under different exercise loads ( F=53.22, 45.33, 3.65, 23.19, P<0.001, <0.001, =0.011, <0.001). Compared with the resting state, subjects showed increased heart rate and LVEF and a decreased EMAT and LVET during exercise loading, all of which were statistically significant ( P<0.01 or 0.05). In the correlation analysis, LVEF was negatively correlated with EMAT and LVEF ( r=-0.415, -0.758, P=0.002,<0.001), and positively correlated with the amplitude of the first heart sound ( r=0.606, P<0.001). The model for predicting LVEF was established by EMAT and LVET, and the multiple regression model was LVEF=108.698-0.092×LVET-0.134×EMAT ( r=0.87, P<0.001). Conclusions:The synchronous monitoring technology of cardiac sounds and ECG signals can continuously and non-invasively monitor LVEF changes during exercise. LVET is the most closely related to LVEF. LVEF is hopeful to predict the changes of cardiac function of astronauts in spaceflight activities.

Objective:To provide references for achieving long time continuous monitoring of cardiac functional changes of astronauts in spaceflight activities through continuously noninvasive assessment of left ventricular systolic function under exercise load by wearable cardiac sounds and ECG signals synchronization monitoring technology.Methods:Eleven healthy male youths were recruited for the study, and they did incremental load exercise on the recumbent power bicycle, starting at 50 W, increasing by 25 W every 3 minutes, until the maximum of 125 W reached. The subjects′ cardiac sounds and ECG signals at rest, 1 min after each level of load during exercise and 3 min after the end of exercise were selected; the transthoracic cardiac ultrasound examination of subjects was performed before and 5 min after exercise. The correlation between the cardiac sounds and ECG signals and left ventricular ejection fraction (LVEF) was analyzed, and a regression model was established to predict LVEF during exercise.Results:There were significant differences in heart rate, LVEF, electro-mechanical activation time (EMAT) and left ventricular ejection time (LVET) of subjects under different exercise loads ( F=53.22, 45.33, 3.65, 23.19, P<0.001, <0.001, =0.011, <0.001). Compared with the resting state, subjects showed increased heart rate and LVEF and a decreased EMAT and LVET during exercise loading, all of which were statistically significant ( P<0.01 or 0.05). In the correlation analysis, LVEF was negatively correlated with EMAT and LVEF ( r=-0.415, -0.758, P=0.002,<0.001), and positively correlated with the amplitude of the first heart sound ( r=0.606, P<0.001). The model for predicting LVEF was established by EMAT and LVET, and the multiple regression model was LVEF=108.698-0.092×LVET-0.134×EMAT ( r=0.87, P<0.001). Conclusions:The synchronous monitoring technology of cardiac sounds and ECG signals can continuously and non-invasively monitor LVEF changes during exercise. LVET is the most closely related to LVEF. LVEF is hopeful to predict the changes of cardiac function of astronauts in spaceflight activities.

Objective To observe the protective effects of oral immunization with Helicobacter pylori (Hp) lysates in combination with mucosal adjuvant dmLT (double mutant heat-labile toxin) against Hp infection in a BALB/ c mouse model and to analyze the features of induced immune responses. Methods BALB/ c mice were orally immunized with Hp lysate (Sydney strain 1, SS1 strain) and dmLT adjuvant, and then innoculated with live Hp strains through oral gavage. A control group was set up by oral administration of normal saline (200 μl/ mouse). The colonization of Hp strains in the stomachs of mice was measured six weeks after bacterial inoculation. Samples of serum, spleen, mesenteric lymph node (MLN), small intes-tine, cecum and feces were collected from mice to analyze the features of induced immune responses. Re-sults The colonization of Hp strains in the stomachs of the immunized mice was significantly decreased as compared with that of the control group. Increased specific IgG antibody responses which were predominantly of IgG1 subtype were detected in the serum samples of the immunized mice and the IgG1 / IgG2a ratio was significantly higher than that of the control group. Elevated secretory IgA (sIgA) was detected in the samples of small intestine, cecum and feces in the immunization group, especially in the small intestine samples, while no significant change in sIgA secretion was observed in the control group. The percentages of IL-17+CD4+ T cells in spleen and mesenteric lymph nodes of the immunization group were significantly higher than those of the control group. Conclusions Oral immunization with Hp lysates in combination with adjuvant dmLT induced mucosal and systemic immune responses and enhanced the resistance to Hp colonization in BALB/ c mice, which was associated with the significantly increased Th17 immune responses and Th2 polari-zation. This study provided reference for further evaluation of dmLT as a mucosal adjuvant in the develop-ment of recombinant protein vaccines against Hp infection.

Objective To evaluate the adjuvant activities of cyclic guanosine monophosphate-adenosine monophosphate ( cGAMP) in enhancing humoral and cellular responses against Helicobacter pylori ( H. pylori) . Methods BALB/c mice were immunized with the protein antigens including UreA, UreB and NapA of H. pylori in combination with cGAMP as the adjuvant on 0 d and 14 d by subcutaneous administra-tion. Then, the serum-specific antibody responses were evaluated by ELISA. Flow cytometry ( FCM) and enzyme-linked immunospot assay ( ELISpot) were used to detect the cellular immune responses occurred in spleen and mesenteric lymph nodes (MLN). Results Subcutaneous administration of protein antigens of H. pylori together with cGAMP induced strong humoral and cellular immune responses in BALB/c mice. The levels of serum-specific IgG antibodies induced by adding cGAMP as the adjuvant were significantly higher than those by immunizing with antigens alone. The levels of splenic IFN-γ-producing lymphocytes in re-sponse to H. pylori antigens and cGAMP immunization were significantly higher than those in the correspond-ing groups without using cGAMP. Conclusion By using cGAMP as an adjuvant, H. pylori antigens could elicit significantly stronger humoral and cellular immune responses in mice than those induced by the anti-gens only. As a stable small molecular compound with strong adjuvant activity, cGAMP has the potential to be used for the development of H. pylori vaccine.

Objective To evaluate the immunopotentiating effect of cyclic guanosine monophos-phate-adenosine monophosphate (cGAMP) as an adjuvant on norovirus (GⅡ. 4) virus like particles (VLPs) in the development of norovirus vaccine. Methods BALB/c mice were intramuscularly immunized with norovirus (GⅡ.4) VLPs composed of capsid protein VP1 in combination with cGAMP or Al(OH)3. Norovirus VLPs-specific antibodies in serum were detected by ELISA. A synthetic histo-blood group antigen (HBGA)-VLPs blocking assay was used to analyze neutralizing antibodies against norovirus VLPs in serum samples. Results Immunization with norovirus VLPs in the presence of cGAMP induced a strong humoral immune response in BALB/c mice. Levels of specific IgG antibodies in serum induced by using cGAMP as the adjuvant were significantly higher than those induced by using Al(OH)3adjuvant when immunization of BALB/c mice with the same dosage of VLPs. The antibody level induced by 1 μg of VLPs in combination with cGAMP was equivalent to that elicited by 10 μg of VLPs combined with Al(OH)3adjuvant. Results of the synthetic HBGA-VLPs blocking assay showed that the blocking rate in cGAMP+VLPs immunization group were significantly higher than that in Al(OH)3+VLPs immunization group when using the same dosage of VLPs. No significant difference in blocking rate was observed between cGAMP+VLPs(1 μg) and Al(OH)3+VLPs (10 μg) immunization groups. Conclusion cGAMP significantly enhanced the specific humoral immune response induced by norovirus (GⅡ.4) VLPs in mice as compared with Al(OH)3adjuvant. It might be used as a novel adjuvant to replace the traditional aluminum adjuvant in the development of norovir-us vaccine.