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.

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

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.

We report a case of chromoblastomycosis caused by , which was successfully treated by long-pulsed 1064 nm Nd: YAG laser combined with terbinafine. A 60-year-old man was admitted for the presence of a 30 mm×40 mm erythematous plaque on the dorsum of his right hand for about 10 months without any subjective symptoms. Both microscopic examination and tissue biopsy of the lesion showed characteristic sclerotic bodies of chromoblastomycosis. Lesion tissue culture on SDA at 26 ℃ for 2 weeks resulted in a black colony, and slide culture identified the isolate as Fonsecaea species. ITS sequence analysis of the isolate showed a 99% homology with strain KX078407. The susceptibility of the isolate to 9 antifungal agents was determined using the microdilution method according to the guidelines of CLSI M38-A2 protocol, and terbinafine showed the lowest MIC (0.125 μg/ml). We subsequently established a Wistar rat model of chromoblastomycosis using the clinical isolate and treated the rats with long-pulsed 1064 nm Nd: YAG laser (pulse width of 3.0 ms, fluence of 24 J/cm, spot size of 3 mm, frequency of 4 Hz, repeated 3 times at an interval of 30 s) twice a week for a total of 8 sessions. Although the laser treatment alone was not able to eliminate the fungi, histopathological examination showed the aggregation of numerous lymphocytes in the local affected tissue, indicating an immune response that consequently facilitate the regression of the lesion. The patient was successfully treated by long-pulsed 1064 nm Nd: YAG laser once a week combined with terbinafine (0.25 /bid) for 8 weeks, and follow-up for 20 months did not reveal any signs of recurrence.
Animals ; Chromoblastomycosis ; Humans ; Laser Therapy ; Lasers, Solid-State ; Male ; Middle Aged ; Rats ; Rats, Wistar ; Terbinafine ; Treatment Outcome

Epidermal growth factor (EGF) is an epithelial cell growth factor that can stimulate intestinal development, repair the damage of epidermal cells as well as reduce the incidence of pathogen infection and diarrhea. In order to produce a recombinant Lactobacillus plantarum (L. plantarum) expressing porcine epidermal growth factor (pEGF), we constructed a recombinant vector stably expressing pEGF in L. plantarum strains. First, L. plantarum strain Lp-1 was isolated from intestinal contents of piglets. Then the functional domain of pEGF, M6 precursor protein signal peptide (SP) and super strong constitutive promoter (SCP) were connected with the backbone plasmid pIAβ8 to construct the recombinant vector that was transformed into Lp-1 by electroporation. Afterwards, pEGF was expressed in Lp-1 and detected by Tricine-SDS-PAGE and ELISA. After orally irrigated early-weaned BALB/c mice with the recombinant L. plantarum every morning and late afternoon for 10 consecutive days, body weight, villous height and crypt depth in the intestine were measured to examine the influence of the recombinant bacteria on the intestinal development of early-weaned mice in vivo. Finally, the results of our experiments demonstrated that pEGF was successfully expressed in Lp-1 and the molecular weight of pEGF was 6 kDa. In addition, the recombinant pEGF can enhanced the daily gain and exerted significance influence (P < 0.05) to the small intestinal morphology of early-weaned BALB/c mice. In conclusion, pEGF could be expressed in L. plantarum and the recombinant pEGF possesses good biological activity.
Animals ; Electrophoresis, Polyacrylamide Gel ; Epidermal Growth Factor ; biosynthesis ; Genetic Vectors ; Intestines ; microbiology ; Lactobacillus plantarum ; metabolism ; Mice ; Mice, Inbred BALB C ; Plasmids ; Promoter Regions, Genetic ; Protein Precursors ; Protein Sorting Signals ; Recombinant Proteins ; biosynthesis ; Swine