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Weightlessness in the space environment affects astronauts' learning memory and cognitive function. Repetitive transcranial magnetic stimulation has been shown to be effective in improving cognitive dysfunction. In this study, we investigated the effects of repetitive transcranial magnetic stimulation on neural excitability and ion channels in simulated weightlessness mice from a neurophysiological perspective. Young C57 mice were divided into control, hindlimb unloading and magnetic stimulation groups. The mice in the hindlimb unloading and magnetic stimulation groups were treated with hindlimb unloading for 14 days to establish a simulated weightlessness model, while the mice in the magnetic stimulation group were subjected to 14 days of repetitive transcranial magnetic stimulation. Using isolated brain slice patch clamp experiments, the relevant indexes of action potential and the kinetic property changes of voltage-gated sodium and potassium channels were detected to analyze the excitability of neurons and their ion channel mechanisms. The results showed that the behavioral cognitive ability and neuronal excitability of the mice decreased significantly with hindlimb unloading. Repetitive transcranial magnetic stimulation could significantly improve the cognitive impairment and neuroelectrophysiological indexes of the hindlimb unloading mice. Repetitive transcranial magnetic stimulation may change the activation, inactivation and reactivation process of sodium and potassium ion channels by promoting sodium ion outflow and inhibiting potassium ion, and affect the dynamic characteristics of ion channels, so as to enhance the excitability of single neurons and improve the cognitive damage and spatial memory ability of hindlimb unloading mice.
Subject(s)
Animals , Mice , Transcranial Magnetic Stimulation , Hindlimb Suspension , Neurons , Cognitive Dysfunction , BrainABSTRACT
Transcranial magnetic stimulation (TMS) as a noninvasive neuromodulation technique can improve the impairment of learning and memory caused by diseases, and the regulation of learning and memory depends on synaptic plasticity. TMS can affect plasticity of brain synaptic. This paper reviews the effects of TMS on synaptic plasticity from two aspects of structural and functional plasticity, and further reveals the mechanism of TMS from synaptic vesicles, neurotransmitters, synaptic associated proteins, brain derived neurotrophic factor and related pathways. Finally, it is found that TMS could affect neuronal morphology, glutamate receptor and neurotransmitter, and regulate the expression of synaptic associated proteins through the expression of brain derived neurotrophic factor, thus affecting the learning and memory function. This paper reviews the effects of TMS on learning, memory and plasticity of brain synaptic, which provides a reference for the study of the mechanism of TMS.
Subject(s)
Humans , Brain , Learning , Neuronal Plasticity , Transcranial Magnetic StimulationABSTRACT
Objective:To explore the peripheral blood levels changes of soluble glycosylation end product receptor (sRAGE), endotoxin and Toll-like receptor (TLR) in patients with severe acute pancreatitis (SAP) complicated with peritoneal cavity infection, and clarify the relationship between indexes and pathogenetic condition.Methods:The clinical data of 105 patients with SAP in Shanghai Pudong New Area People′s Hospital from January 2017 to December 2020 were retrospectively analyzed. Among them, 28 cases had peritoneal cavity infection (infection group), and 77 cases had peritoneal cavity infection symptoms but undiagnosed (non-infection group). The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) at admission was recorded. When patients had the suspected symptoms and signs of peritoneal cavity infection, the serum levels of sRAGE, endotoxin, TLR4 and TLR9 were detected by enzyme-linked immunosorbent assay. The correlation between serum levels of sRAGE, endotoxin, TLR-4, TLR-9 and APACHE Ⅱ was analyzed by Pearson analysis; the risk factors of peritoneal cavity infection in SAP patients were analyzed by multivariate Logistic regression; the receiver operating characteristic (ROC) curve was drawn, and the diagnostic efficacy of serum sRAGE, endotoxin, TLR-4 and TLR-9 in peritoneal cavity infection were evaluated in patients with SAP; the Kaplan-Meier survival curve was drawn, and the comparison used log-rank test.Results:The serum sRAGE, endotoxin, TLR-4 and TLR-9 in infection group were significantly higher than those in non-infection group: (822.16 ± 104.51) ng/L vs. (728.09 ± 96.47) ng/L, (62.59 ± 20.11) ng/L vs. (41.62 ± 13.64) ng/L, (45.17 ± 8.54) μg/L vs. (37.34 ± 6.22) μg/L, (26.35 ± 6.73) μg/L vs. (20.02 ± 5.49) μg/L, and there were statistical differences ( P<0.01). Pearson correlation analysis result showed that the serum sRAGE, endotoxin, TLR-4 and TLR-9 were positively correlated with APACHE Ⅱ in patients with SAP ( r = 0.632, 0.556, 0.521 and 0.631; P<0.05). Multivariate Logistic regression analysis result showed that the combined organ function damage, shock, hypoxemia and serum sRAGE, endotoxin, TLR-4 and TLR-9 were independent risk factors of peritoneal cavity infection in patients with SAP ( P<0.05). ROC curve analysis result showed that the area under the curve for the serum sRAGE, endotoxin, TLR-4 and TLR-9 combined diagnosis of peritoneal cavity infection in patients with SAP was the largest, which was 0.910 (95% CI 0.838 to 0.957, P<0.01), with a sensitivity of 82.14% and a specificity of 87.01%. According to the ROC curve cut-off value of serum sRAGE, endotoxin, TLR-4 and TLR-9 (764.58 ng/L, 58.01 ng/L, 40.24 μg/L and 22.61 μg/L), the 28 patients with SAP complicated with peritoneal cavity infection were divided into high levels patients (21, 14, 23 and 22 cases) and low levels patients (7, 14, 5 and 6 cases); Kaplan-Meier survival curve analysis result showed that the 28-day survival rates in patients with high levels of sRAGE, endotoxin, TLR-4 and TLR-9 were significantly lower than those in patients with low levels (61.90% vs. 71.43%, 50.00% vs. 78.57%, 60.87% vs. 80.00% and 59.09% vs. 83.33%), and there were statistical differences ( P<0.05). Conclusions:The serum sRAGE, endotoxin, TLR-4 and TLR-9 have a high combined diagnostic value in SAP complicated with peritoneal cavity infection, and they are all related to the severity of the disease and have a significant impact on survival.
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As a noninvasive neuromodulation technique, transcranial magnetic stimulation (TMS) is widely used in the clinical treatment of neurological and psychiatric diseases, but the mechanism of its action is still unclear. The purpose of this paper is to investigate the effects of different frequencies of magnetic stimulation (MS) on neuronal excitability and voltage-gated potassium channels in the
Subject(s)
Animals , Mice , Action Potentials , Magnetic Phenomena , Mental Disorders , Neurons , Patch-Clamp Techniques , Potassium Channels, Voltage-GatedABSTRACT
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique that has been paid attention to with increasing interests as a therapeutic neural rehabilitative tool. Studies confirmed that high-frequency rTMS could improve the cognitive performance in behavioral test as well as the excitability of the neuron in animals. This study aimes to investigate the effects of rTMS on the cognition and neuronal excitability of Kunming mice during the natural aging. Twelve young mice, 12 adult mice, and 12 aged mice were used, and each age group were randomly divided into rTMS group and control group. rTMS-treated groups were subjected to high-frequency rTMS treatment for 15 days, and control groups were treated with sham stimulation for 15 days. Then, novel object recognition and step-down tests were performed to examine cognition of learning and memory. Whole-cell patch clamp technique was used to record and analyze resting membrane potential, action potential (AP), and related electrical properties of AP of hippocampal dentate gyrus (DG) granule neurons. Data analysis showed that cognition of mice and neuronal excitability of DG granule neurons were degenerated significantly as the age increased. Cognitive damage and degeneration of some electrical properties were alleviated under the condition of high-frequency rTMS. It may be one of the mechanisms of rTMS to alleviate cognitive damage and improve cognitive ability by changing the electrophysiological properties of DG granule neurons and increasing neuronal excitability.
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Objective To analyze the clinical characteristics of the elderly acute pulmonary embolism(APE) patients with normal blood pressure and right ventricular dysfunction(RVD).Methods A total of 133 elderly APE patients with normal blood pressure and RVD were retrospectively analyzed.According to whether or not to merge RVD,patients were divided into the RVD group(n=42)and the non-RVD group(n=91).The incidence of clinical symptoms and signs,the incidence of pulmonary embolism,clinical indicators after thrombolytic therapy,and the incidence of bleeding were compared and analyzed between RVD and non-RVD groups.Results The incidences of syncope(33.3％ or 14/42 vs.7.8％ 7/91),P2 accentuation(45.2％ or 19/42 vs.25.3％ or 23/91),tachycardia(40.5％ or 17/42 vs.20.9％ or 19/91),cyanosis(26.2％ or 11/42 vs.8.8％ or 8/91)and jugular vein filling(11.9％ or 5/42 vs.1.1％ or 1/91)had significant differences between RVD and non-RVD groups(x2 =4.928,4.644,5.410,4.971 and 4.163,all P＜0.05).The incidence of proximal pulmonary embolism was higher in RVD group than in non-RVD group[25(59.5％)vs.8(8.8％),x2 =13.636,P＜0.01],and the incidence of lobar artery embolism was higher in RVD group than in non-RVD group[32 (76.2％)vs.47(51.6％),x2 =9.530,P＜0.01].Thirteen RVD patients received low-molecular-weight heparin anticoagulation combined with thrombolytic therapy,and 29 RVD patients took low-molecular-weight heparin anticoagulant therapy.The pulmonary artery systolic pressure(PASP) and tricuspid regurgitation pressure levels were higher in the thrombolytic therapy group than in the anticoagulant therapy group(t =2.894,2.518 and 1.957,P =0.004,0.015 and 0.026).The incidence of bleeding was higher in the thrombolytic therapy group than in the anticoagulant therapy group (23.1％ vs.10.3 ％,x2 =3.498,P =0.015).Conclusions The right ventricular dysfunction should be confirmed in APE patients with embolism involving proximal pulmonary artery or(and)presenting clinical symptoms or signs such as syncope and tachycardia.The anticoagulation therapy is effective and safe for elderly patients with normal blood pressure and right heart dysfunction without risks for further deterioration.
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Phage display technology is improved in recent years.LoxP-cre system based in vivo recombination is the most important one. From double recombination system to single recombination system,from large scale sample sequencing to visual judgement, in vivo recombination makes it feasible to construct large natural antibody library, and it is favorable to get high affinity antibody. This review introduces the important improvement of in vivo recombination system.
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Objective To evaluate the method of measurement of total scatter calibrate factor (Sc,p). Methods To measure the Sc,p at different depths on central axis of 6?MV, 15?MV photon beams through different ways. Results It was found that the measured data of Sc,p changed with the different depths to a range of 1%～7%. Using the direct method, the Sc,p measured depth should be the same as the depth in dose normalization point of the prescription dose. If the Sc,p ( fsz, d) was measured at the other depths, it could be obtained indirectly by the calculation formula. Conclusions The Sc,p in the prescription dose can be obtained either by the direct measure method or the indirect calculation formula. But emphasis should be laid on the proper measure depth.