Background Accumulating studies have indicated a wide range of brain alterations with respect to the structure and function of classic trigeminal neuralgia (CTN). Given the dynamic nature of pain experience, the exploration of temporal fluctuations in interregional activity covariance may enhance the understanding of pain processes in the brain. The present study aimed to characterize the temporal features of functional connectivity (FC) states as well as topological alteration in CTN. Methods Resting-state functional magnetic resonance imaging and three-dimensional T1-weighted images were obtained from 41 CTN patients and 43 matched healthy controls (HCs). After group independent component analysis, sliding window based dynamic functional network connectivity (dFNC) analysis was applied to investigate specific FC states and related temporal properties. Then, the dynamics of the whole brain topological organization were estimated by calculating the coefficient of variation of graph-theoretical properties. Further correlation analyses were performed between all these measurements and clinical data. Results Two distinct states were identified. Of these, the state 2, characterized by complicated coupling between default mode network (DMN) and cognitive control network (CC) and tight connections within DMN, was expressed more in CTN patients and presented as increased fractional windows and dwell time. Moreover, patients switched less frequently between states than HCs. Regarding the dynamic topological analysis, disruptions in global graph-theoretical properties (including network efficiency and small-worldness) were observed in patients, coupled with decreased variability in nodal efficiency of anterior cingulate cortex (ACC) in the salience network (SN) and the thalamus and caudate nucleus in the subcortical network (SC). The variation of topological properties showed negative correlation with disease duration and attack frequency. Conclusions The present study indicated disrupted flexibility of brain topological organization under persistent noxious stimulation and further highlighted the important role of “dynamic pain connectome” regions (including DMN/CC/SN) in the pathophysiology of CTN from the temporal fluctuation aspect. Additionally, the findings provided supplementary evidence for current knowledge about the aberrant cortical-subcortical interaction in pain development.

Background. The tumor-infiltrating immune cells are closely associated with the prognosis of gastric cancer (GC). This article is aimed at determining the composition change of immune cells and immune regulatory factors in GC and normal tissues, depicting their prognosis value in GC, and revealing the relationship between them and GC clinical parameters. Methods. We used CIBERSORT to calculate the proportion of 22 immune cells in the GC or normal tissues; a t -test was applied to assess the expression difference of immune cells and immune regulatory factors in normal and GC tissues. The relationship of the immune cells, immune regulatory factors, and GC patients’ clinical characteristics was assessed by univariate analysis. Results. In this study, we found that the proportion of macrophages increased, while plasma cells and monocytes decreased in GC tissues. In these immune fractions, Tregs and naïve B cells were found to be correlated with GC patients’ prognosis. Interestingly, the expression of immune regulatory factors was ambiguous with their classical function in GC tissues. For example, TIM-3, FOXP3, and CMTM6 were overexpressed, while CD27 and PD-1 were underexpressed in GC tissues. We also found that IDO1, PD-1, TIGIT, and TIM-3 were highly expressed in high-grade GC tissues, the HERC2 expression level was related to patients’ gender, and the TIGIT expression level was sensitive to targeted therapy. Furthermore, our results suggested that the infiltration of Tregs and naive B cells was strongly correlated with the T stage, radiation therapy, targeted molecular therapy, and the expression levels of TIM-3 and FOXP3 in GC. Conclusion. The expression pattern of tumor-infiltrating immune cells and immune regulatory factors was systematically depicted in the GC tumor microenvironment, indicating that individualized treatment based on the tumor-infiltrating immune cells and immune regulatory factors may be beneficial to GC patients.

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Time-varying connectivity analyses have indicated idiopathic generalized epilepsy (IGE) could cause significant abnormalities in dynamic connective pattern within and between resting-state sub-networks (RSNs). However, previous studies mainly focused on the IGE-induced dynamic changes of functional connectivity (FC) in specific frequency band (0.01–0.08 Hz or 0.01–0.15 Hz), ignoring the changes across different frequency bands. Here, 24 patients with IGE characterized by juvenile myoclonic epilepsy (JME) and 24 matched healthy controls were studied using a data-driven frequency decomposition approach and a sliding window approach. The RSN dynamics, including intra-RSN dynamics and inter-RSN dynamics, was further calculated to investigate dynamic FC changes within and between RSNs in JME patients in each decomposed frequency band. Compared to healthy controls, JME patients not only showed frequency-dependent decrease in intra-RSN dynamics within multiple RSNs but also exhibited fluctuant alterations in inter-RSN dynamics among several RSNs over different frequency bands especially in the ventral/dorsal attention network and the subcortical network. Additionally, the disease severity had significantly negative correlations with both intra-RSN dynamics within the subcortical network and inter-RSN dynamics between the subcortical network and the default network at the lower frequency band (0.0095–0.0195 Hz). These results suggested that abnormal dynamic FC within and between RSNs in JME occurs at multiple frequency bands and the lower frequency band (0.0095–0.0195 Hz) was probably more sensitive to JME-caused dynamic FC abnormalities. The frequency subdivision and selection are potentially helpful for detecting particular changes of dynamic FC in JME.

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