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BackgroundExcessive inflammation poses significant risks to human physical and mental health. Astilbe grandis, a traditional Miao medicine, is renowned for its anti-inflammatory properties. However, the specific anti-inflammatory effects and mechanisms of many compounds within this plant remain unclear. This study aims to investigate the anti-inflammatory effects and mechanisms of two characteristic oleanane triterpenoids, 3α-acetoxyolean-12-en-27-oic acid (1) and 3β-acetoxyolean-12-en-27-oic acid (2), isolated from Astilbe grandis, using lipopolysaccharide (LPS)-induced Macrophages.MethodsThe anti-inflammatory effects and mechanisms of compounds 1 and 2 were investigated by establishing an LPS-induced inflammation model in RAW 264.7 cells and THP-1 cells. Nitric oxide (NO) levels were assessed using the Griess method. The concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1beta (IL-1β) were measured via enzyme-linked immunosorbent assay (ELISA). The expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was determined using western blotting and quantitative real-time PCR (qRT-PCR). Additionally, the phosphorylation level of p65 in nuclear factor-kappa B (NF-κB) was assessed through western blotting. The nuclear translocation of NF-κB p65 was assessed through immunofluorescence staining. Finally, the binding affinity of the compounds to NF-κB p65 target was validated through molecular docking.ResultsCompounds 1 and 2 significantly inhibited the expression of NO, TNF-α, IL-6, IL-1β, COX-2, and iNOS in LPS-induced Macrophages. Mechanistically, they attenuated the activation of the NF-κB signaling pathway by downregulating the phosphorylation level and nuclear translocation of p65.ConclusionThis study elucidates the anti-inflammatory activities and potential mechanism of the characteristic oleanane triterpenoids with C-14 carboxyl group, compounds 1 and 2, in LPS-induced Macrophages by inhibiting the NF-κB signaling pathway for the first time. These findings suggest that these two compounds hold promise as potential candidates for anti-inflammatory interventions in the future.

Pancreatic cancer is a highly malignant tumor known for its extremely low survival rate. The combination of genetic disorders within pancreatic cells and the tumor microenvironment contributes to the emergence and progression of this devastating disease. Extensive research has shed light on the nature of the microenvironmental cells surrounding the pancreatic cancer, including peripheral nerves and immune cells. Peripheral nerves release neuropeptides that directly target pancreatic cancer cells in a paracrine manner, while immune cells play a crucial role in eliminating cancer cells that have not evaded the immune response. Recent studies have revealed the intricate interplay between the nervous and immune systems in homeostatic condition as well as in cancer development. In this review, we aim to summarize the function of nerves in pancreatic cancer, emphasizing the significance to investigate the neural-immune crosstalk during the advancement of this malignant cancer.

ObjectiveTo evaluate the policy effect of replacing hospitalization service with outpatient service and reducing diabetes-related avoidable hospitalizations by improving outpatient benefits package.MethodsA database of hospital discharge from 2015 to 2017 in City Z was used. All diabetic inpatient cases enrolled in Urban Employee Basic Medical Insurance were selected as the intervention group, and diabetic inpatient cases enrolled in Urban and Rural Resident Basic Medical Insurance were selected as the control group. The Difference-in-Difference model was used to analyze the effect of improving outpatient benefits package level of diabetes from 1800 yuan (about $252.82) to 2400 yuan (about $337.09) per capita per year on avoidable hospitalization rate, average hospitalization cost and average length of stay.ResultsThe avoidable hospitalization rate of diabetes mellitus decreased by 0.21 percentage points (P < 0.01), the average total cost of hospitalization increased by 7.89% (P < 0.01), and the average length of stay per hospitalization increased by 5.63% (P < 0.01).ConclusionsImproving the outpatient benefits package of diabetes can play a role in replacing hospitalization service with outpatient service, reducing diabetes-related avoidable hospitalizations, and reducing the disease burden and financial burden.

Modern oncology increasingly relies on pathological, molecular, and genomic assessments of biopsied tumor tissue. However, the concern for bleeding complication and malignant seeding severely hinders the application of the biopsy tumor. Here, we developed a 16 G biopsy needle to contain two electrodes insulated from each other and connect to an radiofrequency generator. For evaluating hemostatic efficacy, 50 rabbits were randomly divided into two groups: warfarinization and non-warfarinization group. Two liver biopsies and two splenic biopsies per animal were performed using a 16 G biopsy needle. Each group was further equally divided into five groups according to different hemostatic measures, including non-intervention, embolization using an absorbable gelatin sponge, and ablation by RF with three different needle temperatures (50°C, 70°C, and 90°C). Than, we used VX2 rabbit models (n = 25) and applied the five analogous biopsies to the tumor. The flush fluid from the biopsy needle underwent cytomorphological analysis. Our results that the groups using ablation by RF showed significantly less blood loss than the control group for liver and spleen in both groups (P < 0.001). After RF ablation, thermal coagulation of the tissue surrounding the needle tract was observed on both the macroscopic and histological level. Cytological smears showed that tumor cells were degenerated after RF at 70°C and 90°C. Our findings showed that bipolar RF biopsy needle is a promising tool for reducing hemorrhage after biopsy and avoiding implanting tumor cells in the tract.

Diabetic nephropathy (DN), a common microvascular complication of diabetes, is one of the main causes of end-stage renal failure (ESRD) and imposes a heavy medical burden on the world. Yiqi Jiedu Huayu decoction (YJHD) is a traditional Chinese medicine formula, which has been widely used in the treatment of DN and has achieved stable and reliable therapeutic effects. However, the mechanism of YJHD in the treatment of DN remains unclear. This study aimed to investigate the mechanism of YJHD in the treatment of DN. Sprague-Dawley rats were randomly divided into a normal control group, a diabetic group, an irbesartan group, and three groups receiving different doses of YJHD. Animal models were constructed using streptozotocin and then treated with YJHD for 12 consecutive weeks. Blood and urine samples were collected during this period, and metabolic and renal function was assessed. Pathological kidney injury was evaluated according to the kidney appearance, hematoxylin-eosin staining, Masson staining, periodic-acid Schiff staining, periodic-acid Schiff methenamine staining, and transmission electron microscopy. The expression levels of proteins and genes were detected by immunohistochemistry, western blotting, and real-time qPCR. Our results indicate that YJHD can effectively improve renal function and alleviate renal pathological injury, including mesangial matrix hyperplasia, basement membrane thickening, and fibrosis. In addition, YJHD exhibited podocyte protection by alleviating podocyte depletion and morphological damage, which may be key in improving renal function and reducing renal fibrosis. Further study revealed that YJHD upregulated the expression of the autophagy-related proteins LC3II and Beclin-1 while downregulating p62 expression, suggesting that YJHD can promote autophagy. In addition, we evaluated the activity of the mTOR pathway, the major signaling pathway regulating the level of autophagy, and the upstream PI3K/Akt and AMPK pathways. YJHD activated the AMPK pathway while inhibiting the PI3K/Akt and mTOR pathways, which may be crucial to its promotion of autophagy. In conclusion, our study shows that YJHD further inhibits the mTOR pathway and promotes autophagy by regulating the activity of the PI3K/Akt and AMPK pathways, thereby improving podocyte injury, protecting renal function, and reducing renal fibrosis. This study provides support for the application of and further research into YJHD.

Background: Demyelinating disease of the central nervous system is one of the most common neurological diseases and effective treatment is still under in-depth research. Our previous study showed that Angiostrongylus cantonensis infection can induce demyelination injury in mouse brains and IL-17A expression was shown to be significantly increased during this process. Moreover, we found that IL-17A inhibition attenuated the demyelination caused by A. cantonensis infection. However, the underlying mechanisms have not yet been fully elucidated. Methods: IL-17A neutralizing antibodies were injected into A. cantonensis infected mice to decrease IL-17A levels. The activation of glial cells in the brain and the expression of cell markers were detected by a variety of methods, including real-time quantitative PCR, western blotting, and immunofluorescence staining. The relationship between IL-17A and astrocyte activation was further identified by in vitro experiments. The role of SOCS3 in the IL-17A stimulating process was determined using RNA-seq data collection of infected mice and the siRNA interference method. Results: Demyelination of the corpus callosum was relieved after administration of IL-17A neutralizing antibody and this was accompanied by decreased activation of A1 type astrocytes around this region. The expression of SOCS3 was attenuated and activation of astrocytes by IL-17A was mediated by the IL-17RA/STAT3/SOCS3 pathway. IL-17A not only directly damaged oligodendrocytes but also indirectly damaged oligodendrocytes through A1 astrocyte mediation. Specific siRNA inhibition of IL-17A-inducible SOCS3 in astrocytes alleviated their damaging effects on oligodendrocytes. Conclusion: IL-17A plays an important role in demyelination induced by A. cantonensis infection via the IL-17RA/STAT3/SOCS3 pathway in A1-type astrocytes, indicating that specific blockage of IL-17A and SOCS3 activity could be a therapeutic strategy for neuroinflammatory demyelinating diseases associated with astrocyte activation. [ABSTRACT FROM AUTHOR]

Background: The treatment of patients in a minimally conscious state (MCS) remains challenging. Transcranial direct current stimulation (tDCS) is a non-invasive therapeutic method in treating neurologic diseases by regulating the cortical excitability. The aim is to investigate the effect of tDCS in patients with MCS in this study. Methods: Eleven patients in MCS were enrolled in the study. All the patients received 5 daily sessions of 20-min sham tDCS, followed by 10 sessions of 20-min real tDCS. The anodal electrode and cathodal electrodes were placed over the left dorsolateral prefrontal cortex (DLPFC) and the right eyebrow, respectively. Assessment of Coma Recovery Scale-Revised (CRS-R) scores and resting-state functional MRI (rs-fMRI) scans was conducted three times in each patient: before tDCS (baseline, T0), post-sham tDCS at week 1 (T1), and post-real tDCS at week 2 (T2). The whole-brain functional connectivity (FC) was obtained by bilaterally computing FC from six seed regions: precuneus, middle frontal gyrus, supplemental motor area, angular gyrus, superior temporal gyrus, and occipital lobe. One-way repeated measure ANOVA was used to compare the differences of CRS-R scores and FC at T0, T1, and T2. The false discovery rate correction of p < 0.001 was adopted for controlling multiple comparisons in FC analysis. Results: Five patients with MCS showed obvious clinical improvement represented by increased CRS-R scores post- 2-week real tDCS. The CRS-R scores did not change post- 1-week sham treatment. No side effects were reported during the study. The FC of the bilateral supplementary motor area, right angular gyrus, and right superior temporal gyrus were significantly enhanced after 2-week real tDCS compared with that after 1-week sham-tDCS. In addition, FC of bilateral occipital lobe and right precuneus were significantly enhanced post- 2-week real tDCS compared with the baseline. Conclusion: Our findings indicated that tDCS over DLPFC could serve as a potentially effective therapy for improving the consciousness state in patients with MCS. The FC in rs-fMRI can be modulated by tDCS at both the stimulation site (left DLPFC) and the distant regions. [ABSTRACT FROM AUTHOR]

Objective: Intermittent theta burst stimulation (iTBS) has been widely used as a neural modulation approach in stroke rehabilitation. Concurrent use of transcranial magnetic stimulation and electroencephalography (TMS-EEG) offers a chance to directly measure cortical reactivity and oscillatory dynamics and allows for investigating neural effects induced by iTBS in all stroke survivors including individuals without recordable MEPs. Here, we used TMS-EEG to investigate aftereffects of iTBS following stroke. Methods: We studied 22 stroke survivors (age: 65.2 ± 11.4 years; chronicity: 4.1 ± 3.5 months) with upper limb motor deficits. Upper-extremity component of Fugl-Meyer motor function assessment and action research arm test were used to measure motor function of stroke survivors. Stroke survivors were randomly divided into two groups receiving either Active or Sham iTBS applied over the ipsilesional primary motor cortex. TMS-EEG recordings were performed at baseline and immediately after Active or Sham iTBS. Time and time-frequency domain analyses were performed for quantifying TMS-evoked EEG responses. Results: At baseline, natural frequency was slower in the ipsilesional compared with the contralesional hemisphere (P = 0.006). Baseline natural frequency in the ipsilesional hemisphere was positively correlated with upper limb motor function following stroke (P = 0.007). After iTBS, natural frequency in the ipsilesional hemisphere was significantly increased (P < 0.001). Conclusions: This is the first study to investigate the acute neural adaptations after iTBS in stroke survivors using TMS-EEG. Our results revealed that natural frequency is altered following stroke which is related to motor impairments. iTBS increases natural frequency in the ipsilesional motor cortex in stroke survivors. Our findings implicate that iTBS holds the potential to normalize natural frequency in stroke survivors, which can be utilized in stroke rehabilitation. [ABSTRACT FROM AUTHOR]

Objective: Intermittent theta burst stimulation (iTBS) is a special form of repetitive transcranial magnetic stimulation (rTMS), which effectively increases cortical excitability and has been widely used as a neural modulation approach in stroke rehabilitation. As effects of iTBS are typically investigated by motor evoked potentials, how iTBS influences functional brain network following stroke remains unclear. Resting-state electroencephalography (EEG) has been suggested to be a sensitive measure for evaluating effects of rTMS on brain functional activity and network. Here, we used resting-state EEG to investigate the effects of iTBS on functional brain network in stroke survivors. Methods: We studied thirty stroke survivors (age: 63.1 ± 12.1 years; chronicity: 4.0 ± 3.8 months; UE FMA: 26.6 ± 19.4/66) with upper limb motor dysfunction. Stroke survivors were randomly divided into two groups receiving either Active or Sham iTBS over the ipsilesional primary motor cortex. Resting-state EEG was recorded at baseline and immediately after iTBS to assess the effects of iTBS on functional brain network. Results: Delta and theta bands interhemispheric functional connectivity were significantly increased after Active iTBS (P = 0.038 and 0.011, respectively), but were not significantly changed after Sham iTBS (P = 0.327 and 0.342, respectively). Delta and beta bands global efficiency were also significantly increased after Active iTBS (P = 0.013 and 0.0003, respectively), but not after Sham iTBS (P = 0.586 and 0.954, respectively). Conclusion: This is the first study that used EEG to investigate the acute neuroplastic changes after iTBS following stroke. Our findings for the first time provide evidence that iTBS modulates brain network functioning in stroke survivors. Acute increase in interhemispheric functional connectivity and global efficiency after iTBS suggest that iTBS has the potential to normalize brain network functioning following stroke, which can be utilized in stroke rehabilitation. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) has a wide range of clinical applications, and there is growing interest in neural oscillations and corticospinal excitability determined by TMS. Previous studies have shown that corticospinal excitability is influenced by fluctuations of brain oscillations in the sensorimotor region, but it is unclear whether brain network activity modulates corticospinal excitability. Here, we addressed this question by recording electroencephalography (EEG) and TMS measurements in 32 healthy individuals. The resting motor threshold (RMT) and active motor threshold (AMT) were determined as markers of corticospinal excitability. The least absolute shrinkage and selection operator (LASSO) was used to identify significant EEG metrics and then correlation analysis was performed. The analysis revealed that alpha2 power in the sensorimotor region was inversely correlated with RMT and AMT. Innovatively, graph theory was used to construct a brain network, and the relationship between the brain network and corticospinal excitability was explored. It was found that the global efficiency in the theta band was positively correlated with RMT. Additionally, the global efficiency in the alpha2 band was negatively correlated with RMT and AMT. These findings indicated that corticospinal excitability can be modulated by the power spectrum in sensorimotor regions and the global efficiency of functional networks. EEG network analysis can provide a useful supplement for studying the association between EEG oscillations and corticospinal excitability. [ABSTRACT FROM AUTHOR]

Region-specific plasticity in the striatal circuit plays an important role in the development and long-term maintenance of skills and sequential movement procedures. Studies investigating the molecular substrates that contribute to the plasticity changes during motor skill processes have documented a transition in expression from the dorsomedial striatum (DMS) to the dorsolateral striatum (DLS); however, few studies have explored the expression pattern of molecular substrates in the dorsal striatum during progression of instrumental learning. To address this issue, the activity-regulated cytoskeleton-associated protein (Arc) expressions in the subregional dorsal striatum were analyzed during the early and late learning phases of the 10-day sucrose self-administration process. We found that Arc protein is primarily detected in the DMS only in the initial learning stage; however, it is expressed in the DLS during both early and late learning stages. Moreover, Arc expression in the DMS correlated with the number of rewards received later in the training. These data indicated that the Arc expression in subregions of the dorsal striatum shows region-specific transfer and that Arc expression in the DMS contributes to obtaining reward in later learning stage during the process of instrumental learning. [ABSTRACT FROM AUTHOR]

Objective: Brain-computer interface (BCI) training is becoming increasingly popular in neurorehabilitation. However, around one third subjects have difficulties in controlling BCI devices effectively, which limits the application of BCI training. Furthermore, the effectiveness of BCI training is not satisfactory in stroke rehabilitation. Intermittent theta burst stimulation (iTBS) is a powerful neural modulatory approach with strong facilitatory effects. Here, we investigated whether iTBS would improve BCI accuracy and boost the neuroplastic changes induced by BCI training. Methods: Eight right-handed healthy subjects (four males, age: 20–24) participated in this two-session study (BCI-only session and iTBS+BCI session in random order). Neuroplastic changes were measured by functional near-infrared spectroscopy (fNIRS) and single-pulse transcranial magnetic stimulation (TMS). In BCI-only session, fNIRS was measured at baseline and immediately after BCI training. In iTBS+BCI session, BCI training was followed by iTBS delivered on the right primary motor cortex (M1). Single-pulse TMS was measured at baseline and immediately after iTBS. fNIRS was measured at baseline, immediately after iTBS, and immediately after BCI training. Paired-sample t -tests were used to compare amplitudes of motor-evoked potentials, cortical silent period duration, oxygenated hemoglobin (HbO2) concentration and functional connectivity across time points, and BCI accuracy between sessions. Results: No significant difference in BCI accuracy was detected between sessions (p > 0.05). In BCI-only session, functional connectivity matrices between motor cortex and prefrontal cortex were significantly increased after BCI training (p 's < 0.05). In iTBS+BCI session, amplitudes of motor-evoked potentials were significantly increased after iTBS (p 's < 0.05), but no change in HbO2 concentration or functional connectivity was observed throughout the whole session (p 's > 0.05). Conclusions: To our knowledge, this is the first study that investigated how iTBS targeted on M1 influences BCI accuracy and the acute neuroplastic changes after BCI training. Our results revealed that iTBS targeted on M1 did not influence BCI accuracy or facilitate the neuroplastic changes after BCI training. Therefore, M1 might not be an effective stimulation target of iTBS for the purpose of improving BCI accuracy or facilitate its effectiveness; other brain regions (i.e., prefrontal cortex) are needed to be further investigated as potentially effective stimulation targets. [ABSTRACT FROM AUTHOR]

Innate immune memory is a part of the innate immune system that facilitates the elimination of pathogens. However, it may exacerbate neuropathology. In this study, we found that innate immune memory is detrimental in stroke, because it promotes the acute immune response and exacerbates ischemic infarcts. Mesenchymal stem cell therapy has been widely studied for its therapeutic potential in various diseases including stroke, but whether it diminishes innate immune memory has not been studied. Here, our study demonstrates that, after the activation of innate immune memory by lipopolysaccharide, mesenchymal stem cell therapy can diminish innate immune memory though down-regulation of H3 methylation and subsequently protect against stroke. Our results demonstrate that innate immune memory is detrimental in stroke, and we describe a novel potential therapeutic target involving the use of mesenchymal stem cells to treat stroke patients. [ABSTRACT FROM AUTHOR]

Background: Observation of a goal-directed motor action can excite the respective mirror neurons, and this is the theoretical basis for action observation (AO) as a novel tool for functional recovery during stroke rehabilitation. To explore the therapeutic potential of AO for dysphagia, we conducted a task-based functional magnetic resonance imaging (fMRI) study to identify the brain areas activated during observation and execution of swallowing in healthy participants. Methods: Twenty-nine healthy volunteers viewed the following stimuli during fMRI scanning: an action-video of swallowing (condition 1, defined as AO), a neutral image with a Chinese word for "watching" (condition 2), and a neutral image with a Chinese word for "swallowing" (condition 3). Action execution (AE) was defined as condition 3 minus condition 2. One-sample t -tests were performed to define the brain regions activated during AO and AE. Results: Many brain regions were activated during AO, including the middle temporal gyrus, inferior frontal gyrus, pre- and postcentral gyrus, supplementary motor area, hippocampus, brainstem, and pons. AE resulted in activation of motor areas as well as other brain areas, including the inferior parietal lobule, vermis, middle frontal gyrus, and middle temporal gyrus. Two brain areas, BA6 and BA21, were activated with both AO and AE. Conclusion: The left supplementary motor area (BA6) and left middle temporal gyrus (BA21), which contains mirror neurons, were activated in both AO and AE of swallowing. In this study, AO activated mirror neurons and the swallowing network in healthy participants, supporting its potential value in the treatment of dysphagia. [ABSTRACT FROM AUTHOR]

Theta-burst stimulation (TBS), a variant of repetitive transcranial magnetic stimulation (rTMS), can potentially benefit the treatment of swallowing disorders. However, the after-effects of TBS on the swallowing motor cortex remain uncertain. The newly developed graph-based analysis of the centrality approach has been increasingly used to explore brain networks. The purpose of this study was to identify degree centrality (DC) alterations in the brain network after different TBS protocols were performed over the suprahyoid muscles motor cortex in healthy subjects. A total of 40 right-handed healthy subjects (mean age: 23.73 ± 2.57 years, range: 21–30, 20 females) were included in this study and randomly assigned to two groups, including the continuous TBS (cTBS) group and the intermittent TBS (iTBS) group. All of the subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning before and after TBS implementation. Compared to the baseline, cTBS resulted in increased DC values in the left inferior frontal gyrus (P < 0.01). In the iTBS group, decreased DC was observed in the left cerebellum and left medial frontal gyrus; However, increased DC was observed in several brain areas including the right superior temporal gyrus, right superior frontal gyrus, right postcentral gyri and left paracentral lobule (P < 0.01). These results indicated that cTBS mainly results in increasing DC in the ipsilateral. However, iTBS is capable of facilitating the excitability of the swallowing motor cortex and increasing the connectivity of multiple brain regions, including the bilateral sensorimotor network, and might have therapeutic potential in the treatment of swallowing disorders. [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation (rTMS) technology, which is amongst the most used non-invasive brain stimulation techniques currently available, has developed rapidly from 2009 to 2018. However, reports on the trends of rTMS using bibliometric analysis are rare. The goal of the present bibliometric analysis is to analyze and visualize the trends of rTMS, including general (publication patterns) and emerging trends (research frontiers), over the last 10 years by using the visual analytic tool CiteSpace V. Publications related to rTMS from 2009 to 2018 were retrieved from the Web of Science (WoS) database, including 2,986 peer-reviewed articles/reviews. Active authors, journals, institutions, and countries were identified by WoS and visualized by CiteSpace V, which could also detect burst changes to identify emerging trends. GraphPad Prism 8 was used to analyze the time trend of annual publication outputs. The USA ranked first in this field. Pascual-Leone A (author A), Fitzgerald PB (author B), George MS (author C), Lefaucheur JP (author D), and Fregni F (author E) made great contributions to this field of study. The most prolific institution to publish rTMS-related publications in the last decade was the University of Toronto. The journal Brain Stimulation published most papers. Lefaucheur et al.'s paper in 2014, and the keyword "sham controlled trial" showed the strongest citation bursts by the end of 2018, which indicates increased attention to the underlying work, thereby indicating the research frontiers. This study reveals the publication patterns and emerging trends of rTMS based on the records published from 2009 to 2018. The insights obtained have reference values for the future research and application of rTMS. [ABSTRACT FROM AUTHOR]

Contralateral intermittent theta burst stimulation (iTBS) can potentially improve swallowing disorders with unilateral lesion of the swallowing cortex. However, the after-effects of iTBS on brain excitability remain largely unknown. Here, we investigated the alterations of temporal dynamics of inter-regional connectivity induced by iTBS following continuous TBS (cTBS) in the contralateral suprahyoid muscle cortex. A total of 20 right-handed healthy subjects underwent cTBS over the left suprahyoid muscle motor cortex and then immediately afterward, iTBS was applied to the contralateral homologous area. All of the subjects underwent resting-state functional magnetic resonance imaging (Rs-fMRI) pre- and post-TBS implemented on a different day. We compared the static and dynamic functional connectivity (FC) between the post-TBS and the baseline. The whole-cortical time series and a sliding-window correlation approach were used to quantify the dynamic characteristics of FC. Compared with the baseline, for static FC measurement, increased FC was found in the precuneus (BA 19), left fusiform gyrus (BA 37), and right pre/post-central gyrus (BA 4/3), and decreased FC was observed in the posterior cingulate gyrus (PCC) (BA 29) and left inferior parietal lobule (BA 39). However, in the dynamic FC analysis, post-TBS showed reduced FC in the left angular and PCC in the early windows, and in the following windows, increased FC in multiple cortical areas including bilateral pre- and postcentral gyri and paracentral lobule and non-sensorimotor areas including the prefrontal, temporal and occipital gyrus, and brain stem. Our results indicate that iTBS reverses the aftereffects induced by cTBS on the contralateral suprahyoid muscle cortex. Dynamic FC analysis displayed a different pattern of alteration compared with the static FC approach in brain excitability induced by TBS. Our results provide novel evidence for us in understanding the topographical and temporal aftereffects linked to brain excitability induced by different TBS protocols and might be valuable information for their application in the rehabilitation of deglutition. [ABSTRACT FROM AUTHOR]

Theta burst stimulation (TBS) is a powerful variant of repetitive transcranial magnetic stimulation (rTMS), making it potentially useful for the treatment of swallowing disorders. However, how dose TBS modulate human swallowing cortical excitability remains unclear. Here, we aim to measure the after-effects of spontaneous brain activity at resting-state using the regional homogeneity (ReHo) approach in healthy subjects who underwent different TBS protocols over the suprahyoid muscle cortex. Sixty healthy subjects (23.45 ± 2.73 years, 30 males) were randomized into three groups which completed different TBS protocols. The TMS coil was applied over the cortex of the suprahyoid muscles. Data of resting-state functional MRI (Rs-fMRI) of the subjects were acquired before and after TBS. The ReHo was compared across sessions [continuous TBS (cTBS), intermittent TBS (iTBS) and cTBS/iTBS] and runs (pre/post TBS). In the comparison between pre- and post-TBS, increased ReHo was observed in the right lingual gyrus and right precuneus and decreased ReHo in the left cingulate gyrus in the cTBS group. In the iTBS group, increased ReHo values were seen in the pre-/postcentral gyrus and cuneus, and decreased ReHo was observed in the left cerebellum, brainstem, bilateral temporal gyrus, insula and left inferior frontal gyrus. In the cTBS/iTBS group, increased ReHo was found in the precuneus and decreased ReHo in the right cerebellum posterior lobe, left anterior cerebellum lobe, and right inferior frontal gyrus. In the post-TBS inter-groups comparison, increased ReHo was seen in right middle occipital gyrus and decreased ReHo in right middle frontal gyrus and right postcentral gyrus (cTBS vs. cTBS/iTBS). Increased ReHo was shown in left inferior parietal lobule and left middle frontal gyrus (cTBS vs. iTBS). Increased ReHo was shown in right medial superior frontal gyrus and decreased ReHo in right cuneus (cTBS/iTBS vs. iTBS). Our findings indicate cTBS had no significant influence on ReHo in the primary sensorimotor cortex, iTBS facilitates an increased ReHo in the bilateral sensorimotor cortex and a decreased ReHo in multiple subcortical areas, and no reverse effect exhibits when iTBS followed the contralateral cTBS over the suprahyoid motor cortex. The results provide a novel insight into the neural mechanisms of TBS on swallowing cortex. [ABSTRACT FROM AUTHOR]

While increasing evidence demonstrated that voluntary wheel running promotes cognitive function, little is known on how different types of voluntary wheel running affect cognitive function in elderly populations. We investigated the effects of various voluntary wheel-running types on adult hippocampal neurogenesis and spatial cognition in middle-aged mice. Male C57BL6 and Thy1-green fluorescent protein (GFP) transgenic mice (13 months) were equally assigned to one of the following groups: (1) T1: no voluntary wheel running; (2) T2: intermittent voluntary wheel running; and (3) T3: continuous voluntary wheel running. The Thy1-GFP transgenic mice were used to specifically label granule cells, since Thy-1 is a promoter for neuronal expression. Behavioral evaluations suggested that intermittent voluntary wheel running improved Morris water maze performance in middle-aged mice. The number of BrdU-positive cells was significantly higher in both intermittent and continuous voluntary wheel running compared with no voluntary wheel running. However, only intermittent voluntary wheel running facilitated the newborn cells to differentiate into granule cells, while newborn cells tended to differentiate into astrocytes and repopulation of microglia was also enhanced in the continuous voluntary wheel-running group. These results indicated that intermittent voluntary exercise may be more beneficial for enhancing spatial memory. Effective improvement of hippocampal neurogenesis was also caused by intermittent voluntary wheel running in middle-aged mice. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN), a common microvascular complication of diabetes, is one of the main causes of end-stage renal failure (ESRD) and imposes a heavy medical burden on the world. Yiqi Jiedu Huayu decoction (YJHD) is a traditional Chinese medicine formula, which has been widely used in the treatment of DN and has achieved stable and reliable therapeutic effects. However, the mechanism of YJHD in the treatment of DN remains unclear. This study aimed to investigate the mechanism of YJHD in the treatment of DN. Sprague-Dawley rats were randomly divided into a normal control group, a diabetic group, an irbesartan group, and three groups receiving different doses of YJHD. Animal models were constructed using streptozotocin and then treated with YJHD for 12 consecutive weeks. Blood and urine samples were collected during this period, and metabolic and renal function was assessed. Pathological kidney injury was evaluated according to the kidney appearance, hematoxylin-eosin staining, Masson staining, periodic-acid Schiff staining, periodic-acid Schiff methenamine staining, and transmission electron microscopy. The expression levels of proteins and genes were detected by immunohistochemistry, western blotting, and real-time qPCR. Our results indicate that YJHD can effectively improve renal function and alleviate renal pathological injury, including mesangial matrix hyperplasia, basement membrane thickening, and fibrosis. In addition, YJHD exhibited podocyte protection by alleviating podocyte depletion and morphological damage, which may be key in improving renal function and reducing renal fibrosis. Further study revealed that YJHD upregulated the expression of the autophagy-related proteins LC3II and Beclin-1 while downregulating p62 expression, suggesting that YJHD can promote autophagy. In addition, we evaluated the activity of the mTOR pathway, the major signaling pathway regulating the level of autophagy, and the upstream PI3K/Akt and AMPK pathways. YJHD activated the AMPK pathway while inhibiting the PI3K/Akt and mTOR pathways, which may be crucial to its promotion of autophagy. In conclusion, our study shows that YJHD further inhibits the mTOR pathway and promotes autophagy by regulating the activity of the PI3K/Akt and AMPK pathways, thereby improving podocyte injury, protecting renal function, and reducing renal fibrosis. This study provides support for the application of and further research into YJHD. [ABSTRACT FROM AUTHOR]