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 provide the mechanism-based pharmacotherapy of the Huatan Qushi formula (HTQS formula), for the health management and treatment of non-alcoholic fatty liver disease (NAFLD). Methods: A rat model of NAFLD was employed to examine the efficacy and safety of the HTQS formula. In vivo active components and potential mechanisms of the HTQS formula were identified using UPLC‒MS/MS combined with network pharmacology. The influence of the HTQS formula on the dominating proteins in PI3K/Akt pathway was validated in vivo using western blot. Finally, 16S rRNA sequencing of the gut microbiome was conducted followed by targeted metabolomics detecting fecal short-chain fatty acids (SCFAs) and bile acids to determine the impact of the HTQS formula on gut microbiota. Results: The HTQS formula reduced weight gain and hepatic steatosis in NAFLD rats and decreased serum total cholesterol (TC), triglycerides, blood glucose, and insulin resistance (IR) without causing liver or kidney injury. We detected 28 components using UPLC‒MS/MS and identified 439 shared targets between NAFLD and the HTQS formula. Primarily, we focused on the PI3K/Akt signaling pathway based on protein‒protein interaction network analysis. We validated that the HTQS formula inhibited liver steatosis and inflammation by increasing the phosphorylation levels of PI3K, AKT, P27, GSK3β in the PI3K/Akt signaling pathway. 16S rRNA sequencing revealed that the HTQS formula reduced the abundance of the genus Family_XIII_AD3011_group, which was positively correlated with IR and taurodeoxycholic acid. In addition, Lachnospiraceae_UCG_010 inversely correlated with TC and five bile acids, which could be essential to the therapeutic effect of the HTQS formula against NAFLD. Conclusions The HTQS formula proved to be an effective pharmacotherapy for NAFLD without causing liver or kidney injury. Multiple potent components of the HTQS formula could alleviate liver steatosis and lipid metabolism disorder by modulating the PI3K/Akt signaling pathway and restoring gut microbiota composition.

Objective:To explore the relationship between relapse tendency and psychological craving in fe-male methamphetamine(MA)-dependent young adults,focusing on the roles of self-control and future time per-spective.Methods:A total of 340 MA-dependent young adults from two women's compulsory isolation drug reha-bilitation centers in Sichuan Province were included.Participants were assessed with the Relapse Tendency Ques-tionnaire(RTQ),Obsessive Compulsive Drug Use Scale(OCDUS),Drug Abuser Self-Control Ability Question-naire(DASAQ)and General Future Time Perspective Scale(GFTPQ).The moderated mediation model was ana-lyzed by using the SPSS macro program PROCESS(version4.2).Results:The RTQ scores were positively correla-ted with the OCDUS scores(r=0.45,P＜0.001).The DASAQ scores partially mediated the relationship between the scores of OCDUS and RTQ,accounted for 37.91％of the total effect.The GFTP scores moderated the relation-ship between the scores of the OCDUS,DASAQ and RTQ(β=-0.18,0.19,P＜0.001).Conclusion:The influ-ence of psychological craving on relapse tendency in female MA-dependent young adults exhibits a moderated me-diating effect,suggesting the potential of enhancing self-control and future time perspective for preventing relapse and improving detoxification efficiency.

Objective:To develop and evaluate metal artifact removal systems (MARSs) based on deep learning to assess their effectiveness in removing artifacts caused by different thicknesses of metals in cone-beam CT (CBCT) images.Methods:A full-mouth standard model (60 mm×75 mm×110 mm) was three-dimensional (3D) printed using photosensitive resin. The model included a removable and replaceable target tooth position where cobalt-chromium alloy crowns with varying thicknesses were inserted to generate matched CBCT images. The artifacts resulting from cobalt-chromium alloys with different thicknesses were evaluated using the structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR). CNN-MARS and U-net-MARS were developed using a convolutional neural network and U-net architecture, respectively. The effectiveness of both MARSs were assessed through visualization and by measuring SSIM and PSNR values. The SSIM and PSNR values were statistically analyzed using one-way analysis of variance (α=0.05).Results:Significant differences were observed in the range of artifacts produced by different thicknesses of cobalt-chromium alloys (all P<0.05), with 1 mm resulting in the least artifacts. The SSIM values for specimens with thicknesses of 1.0 mm, 1.5 mm, and 2.0 mm were 0.916±0.019, 0.873±0.010, and 0.833±0.010, respectively ( F=447.89, P<0.001). The corresponding PSNR values were 20.834±1.176, 17.002±0.427, and 14.673±0.429, respectively ( F=796.51, P<0.001). After applying CNN-MARS and U-net-MARS to artifact removal, the SSIM and PSNR values significantly increased for images with the same thickness of metal (both P<0.05). When using the CNN-MARS for artifact removal, the SSIM values for 1.0, 1.5 and 2.0 mm were 0.938±0.023, 0.930±0.029, and 0.928±0.020 ( F=2.22, P=0.112), while the PSNR values were 30.938±1.495, 30.578±2.154 and 30.553±2.355 ( F=0.54, P=0.585). When using the U-net-MARS for artifact removal, the SSIM values for 1.0, 1.5 and 2.0 mm were 0.930±0.024, 0.932±0.017 and 0.930±0.012 ( F=0.24, P=0.788), and the PSNR values were 30.291±0.934, 30.351±1.002 and 30.271±1.143 ( F=0.07, P=0.929). No significant differences were found in SSIM and PSNR values after artifact removal using CNN-MARS and U-net-MARS for different thicknesses of cobalt-chromium alloys (all P>0.05). Visualization demonstrated a high degree of similarity between the images before and after artifact removal using both MARSs. However, CNN-MARS displayed clearer metal edges and preserved more tissue details when compared with U-net-MARS. Conclusions:Both the CNN-MARS and U-net-MARS models developed in this study effectively remove the metal artifacts and enhance the image quality. CNN-MARS exhibited an advantage in restoring tissue structure information around the artifacts compared to U-net-MARS.

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