Objective:To observe the effect of repeated, bilateral administration of high-frequency transcranial magnetic stimulation (rTMS) in treating post-stroke dysphagia.Methods:Forty-five persons with post-stroke dysphagia were randomly divided into a bilateral group ( n=14 after one dropout), an affected group ( n=15) and a healthy group ( n=15). All received 30 minutes of conventional swallowing rehabilitation training 5 times a week for 2 weeks from a speech therapist. Those in the affected group also received 5Hz rTMS applied to the motor cortex controlling the suprachyoid muscle group. The bilateral group received the same stimulation bilaterally with the same duration and treatment course. Videofluoroscopy was used to assess their swallowing before and after the 2 weeks of treatment. It was rated using the penetration-aspiration scale (PAS) and the functional swallowing disorder scale (FDS). Surface electromyography was employed to evaluate suprachyoid muscle function. Cortical excitability was assessed by measuring the resting motor threshold (RMT) of the unaffected hemisphere. Results:After the treatment, the average PAS, FDS and muscle function values had improved significantly for all three groups, but significant RMT differences were observed only between the bilateral and the unaffected group. Significant differences in the average FDS and PAS scores were observed after the treatment, as well as significant changes in FDS and muscle function between the affected group and the other two groups. The average FDS scores before and after treatment were significantly different between the unaffected and bilateral group, with the former scoring significantly better than the latter. But no significant differences in the average PAS scores were observed after the treatment.Conclusions:5Hz rTMS of either the unaffected or affected cerebral cortex (or bilateral) can effectively improve the swallowing function of persons with post-stroke dysphagia. Bilateral stimulation has the greatest therapeutic effect, followed by stimulation of the unaffected cerebral cortex.

OBJECTIVETo determine the effects of ginsenosides Rb1(GSRb1) on learning and memory and expression of somatostatin (SS) in the hippocampus and the frontal cortex in rat model of sleep deprivation (SD).

METHODSRats were randomized into groups of SD 2 d, SD 4 d, SD 6 d, and SD 0 d, while each group was sub-divided into GSRb1 group and normal saline (NS) sub-groups. Rats were intraperitoneal administered with 30 mg/(kg*d) of GSRb1 or NS for 7 d, then the learning and memory abilities were examined by measuring average swimming speed and mean escape latency using Morris maze.Expression of somatostatin was detected with immunohistochemical method and image analysis in the hippocampus and the frontal cortex.

RESULTSCompared with SD 0 d rats, SD rats exhibited significant decrease in the average swimming speed and increase in the escape latency (P <0.01). The expression of somatostatin in the hippocampus was decreased significantly in SD 2 d, SD 4 d and SD 6 d rats (P<0.05). However, decrease was only observed in SD 4 d and SD 6 d rats in the frontal cortex (P <0.05). Parallel comparison between NS control and GSRb1 treated rats demonstrated that rats treated with GSRb1 in each subgroup exhibited faster swimming speed and shorter escape latency (P <0.05). Meanwhile, the expression of somatostatin was increased in SD 2 d, SD 4 d and SD 6 d rats in the hippocampus and in SD 4 d and SD 6 d rats in the frontal cortex (P <0.05), respectively.

CONCLUSIONGSRb1 enhances the expression of somatostatin in sleep deprivation rats and subsequently may improve learning and memory abilities of rats.

Animals ; Brain ; metabolism ; Disease Models, Animal ; Ginsenosides ; pharmacology ; Learning ; drug effects ; Male ; Memory ; drug effects ; Rats ; Rats, Sprague-Dawley ; Sleep Deprivation ; metabolism ; Somatostatin ; metabolism

Objective To assess the cardiovascular structure and function in children with confirmed primary hypertension,and to explore the impact of hypertension and related risk factors on cardiovascular structure and function of children.Methods Parameters related to cardiac structure,vascular structure and function were measured in 213 hypertensive children,who were confirmed upon repeated measurements on separate occasions.A total of 197 healthy children were recruited as controls.Results 1) In hypertensive children,left ventricular end-diastolic diameter (LVEDd),left ventricular end-systolic diameter (LVESd),left ventricular mass (LVM),left ventricular mass index (LVMI),left ventricular posterior wall thickness (LVPT) and interventricular septal thickness (IVST) were all significantly higher than their counterparts (P＜0.05).No statistical differences were found in carotid intima-media thickness (cIMT),relative wall thickness (RWT) and brachial ankle pulse wave velocity (ba-PWV).2) Compared with controls,LVEDd,LVESd,LVM,LVMI were all significantly higher in hypertensive children (P＜0.05),regardless of age group or weight-status.No statistical differences were found in ccIMT and RWT,while ba-PWV was statistically higher in controls among children aged 6-12 years.3) Data from multiple linear regression analysis noticed that LVMI was associated with age,sex,BMI and hypertension while RWT was associated with age and BMI.Conclusion In children with primary hypertension,changes of vascular structure and function were not shown but left ventricular remodeling and early changes of function had been developed in children under 12 years old.

Objective:To explore the chain mediating effect of core self-evaluation and social withdrawal on the relationship between peer relationship and depression symptoms of adolescents.Methods:From September 2020 to October 2020, a sample of 1 936 students from grade 4 to grade 9 of different schools completed a cross-section questionnaire survey including the inventory of parent and peer attachment, core self-evaluation scale, child social preference scale-R and depression self-rating scale for children.SPSS 21.0 and SPSS PROCESS macro program were used for data statistics.The statistical methods included analysis of variance, correlation analysis and intermediary effect test.Results:(1) Peer relationship (94.78±17.27) was positively correlated with core self-evaluation (34.14±7.52) ( r=0.50, P<0.01), and negatively correlated with depression (12.21±6.02) and social withdrawal (32.34±11.45) ( r=-0.55, -0.58, both P<0.01). Core self-evaluation was negatively associated with social withdrawal and depression symptoms ( r=-0.48, -0.67, both P<0.01), while social withdrawal and depression was positively correlated ( r=0.54, P<0.01). (2) Peer relationship had a significant direct effect on depression symptoms (the effect value=-0.205, P<0.01). Core self-evaluation and social withdrawal respectively separate mediated the effect of peer relationship on depression symptoms (the effect value=-0.231, -0.088, 95% CI=-0.261--0.202, -0.110--0.068), while the chain mediating effect of the two was significant, and the effect value was -0.025(95% CI=-0.033--0.019). Conclusion:Good peer relationship can lead to higher core self-evaluation and less social withdrawal behaviors in adolescents that serves as buffer from depression.

OBJECTIVE: To determine the correlation of phosphorylated ribosomal S6 protein (P-S6) content in blood and brain tissue in mice and rats with seizure. METHODS: Seizure models were induced by intraperitoric injection of kainic acid (KA) in C57BL/mice and SD rats. Flow cytometry was used to detect the content of P-S6 in blood; Western blot was used to detect the expression of P-S6 in brain tissues. The correlation between P-S6 expression in blood and in brain tissue was examine by Pearson analysis, and the correlation between P-S6 expression in blood and the severity of seizure was also observed. RESULTS: Western blotting analysis showed that the expression of P-S6 was significantly increased in peripheral blood and brain tissue in mice 1 h after KA-induced seizure,and the expression levels increased to (1.49±0.45) times (<0.05) and (2.55±0.66) times ( <0.01) of the control group, respectively. Flow cytometry showed that the positive percentage and average fluorescence intensity of P-S6 in the blood of mice increased significantly 1 h after KA-induced seizures (<0.01), which was consistent with the expression of P-S6 in brain tissue (=0.8474, <0.01). Flow cytometry showed that the average fluorescence intensity of P-S6 in blood increased from 14.89±9.75 to 52.35±21.72 (<0.01) in rats with seizure, which was consistent with the change of P-S6 in brain tissue (=0.9385, <0.01). Rats with higher levels of seizure were of higher levels of P-S6 in peripheral blood. CONCLUSIONS Consistent correlation of P-S6 expression is demonstrated in peripheral blood and in brain tissue after KA-induced seizure, suggesting that the expression of P-S6 in blood can accurately reflect the changes of mTOR signaling pathway in brain tissue.
Animals ; Brain ; drug effects ; physiopathology ; Gene Expression Regulation ; drug effects ; Kainic Acid ; Mice ; Mice, Inbred C57BL ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Seizures ; blood ; chemically induced ; physiopathology

OBJECTIVE: To investigate the efficacy of brain-targeted rapamycin (T-Rap) in treatment of epilepsy in rats. METHODS: Rapamycin nanoparticles targeting brain were prepared. The epilepsy model was induced by injection of pilocarpine in rats. The rats with pilocarpine-induced epilepsy were treated with rapamycin (Rap group) or brain-targeted rapamycin (T-Rap group). Seizure activity was observed by electroencephalography; the effect on mTOR signaling pathway was detected by Western blot; neuronal death and moss fiber sprouting were analyzed by Fluoro-Jade B (FJB) and Timm's staining, respectively. RESULTS: Electroencephalography showed that both preparation of rapamycin significantly reduced the frequency of spontaneous seizures in rats, and the effect of T-Rap was stronger than that of conventional rapamycin (<0.05). Western blot showed that the phosphorylation levels of S6K and S6 in T-Rap group were lower than those in Rap group (all <0.05), indicating that T-Rap had a stronger inhibitory effect on mTOR signaling pathway. FJB staining showed that T-Rap significantly decreased neuronal death, but there was no significant difference as compared with Rap group. Timm's staining showed that both preparations of rapamycin significantly reduced the germination of mossy fibers, while the effect of T-Rap was more pronounced than Rap group (<0.05). The inhibition of body weight gain of T-Rap group was less than that of Rap group (<0.05). CONCLUSIONS T-Rap has a better therapeutic effect on epilepsy than conventional rapamycin with a less adverse effects in rats.
Animals ; Brain ; drug effects ; Disease Models, Animal ; Epilepsy ; chemically induced ; drug therapy ; Neurons ; drug effects ; Pilocarpine ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Sirolimus ; pharmacology ; therapeutic use ; Treatment Outcome

OBJECTIVE: To investigate whether rapamycin treatment starting at 24 h after cerebral ischemia/reperfusion(I/R) has protective effect on brain injury in rats. METHODS: The rat I/R model was established by middle cerebral artery occlusion according to Longa's method. A total of 104 Sprague Dawley rats were randomly divided into sham group, model group, and rapamycin-treated groups (6 h or 24 h after modeling). Neurological function was assessed with neurological severity score (NSS). Triphenyl tetrazolium chloride (TTC) staining and Fluoro-Jade B (FJB) staining were used to examine the infarct volume and neuronal apoptosis, respectively. The expression of p-S6 protein in mTOR signaling pathway was detected by Western blot analysis. RESULTS: Compared with sham group, NSS of the model group was significantly increased and TTC staining indicated obvious infarct area (all <0.01). Furthermore, significantly increased number of FJB-positive cells and p-S6 expression in the penumbra area were shown in the model group (all <0.01). Compared with the model group, both rapamycin-treated groups demonstrated decreased NSS, infarction volume and FJB positive cells as well as p-S6 expression in the penumbra area (<0.05 or <0.01). There was no significant difference between the groups of rapamycin administrated 6 h and 24 h after modeling (all >0.05). CONCLUSIONS Rapamycin treatment starting at 24 h after I/R exhibits protective effect on brain injury in rats.
Animals ; Brain Ischemia ; drug therapy ; Immunosuppressive Agents ; therapeutic use ; Infarction, Middle Cerebral Artery ; drug therapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control ; Sirolimus ; therapeutic use ; Treatment Outcome

CRISPR/Cas9 has been widely used in engineering Saccharomyces cerevisiae for gene insertion, replacement and deletion due to its simplicity and high efficiency. The selectable markers of CRISPR/Cas9 systems are particularly useful for genome editing and Cas9-plasmids removing in yeast. In our previous research, GAL80 gene has been deleted by the plasmid pML104-mediated CRISPR/Cas9 system in an engineered yeast, in order to eliminate the requirement of galactose supplementation for induction. The maximum artemisinic acid production by engineered S. cerevisiae 1211-2 (740 mg/L) was comparable to that of the parental strain 1211 without galactose induction. Unfortunately, S. cerevisiae 1211-2 was inefficient in the utilization of the carbon source ethanol in the subsequent 50 L pilot fermentation experiment. The artemisinic acid yield in the engineered S. cerevisiae 1211-2 was only 20%-25% compared with that of S. cerevisiae 1211. The mutation of the selection marker URA3 was supposed to affect the growth and artemisinic acid production. A ura3 mutant was successfully restored by a recombinant plasmid pML104-KanMx4-u along with a 90 bp donor DNA, resulting in S. cerevisiae 1211-3. This mutant could grow normally in a fed-batch fermentor with mixed glucose and ethanol feeding, and the final artemisinic acid yield (> 20 g/L) was comparable to that of the parental strain S. cerevisiae 1211. In this study, an engineered yeast strain producing artemisinic acid without galactose induction was obtained. More importantly, it was the first report showing that the auxotrophic marker URA3 significantly affected artemisinic acid production in a pilot-scale fermentation with ethanol feeding, which provides a reference for the production of other natural products in yeast chassis.
Artemisinins ; Fermentation ; Saccharomyces cerevisiae/metabolism* ; Saccharomyces cerevisiae Proteins/metabolism*

Male ; Humans ; Aged ; Sleep Duration ; Aging ; Testosterone ; China ; Sleep