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Background The cerebellum plays key roles in the pathology of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), but the way in which these conditions affect how the cerebellum communicates with the rest of the brain (its connectome) and associated genetic correlates remains largely unknown. Methods Combining multimodal MRI data from 208 MS patients, 200 NMOSD patients and 228 healthy controls and brain-wide transcriptional data, this study characterized convergent and divergent alterations in within-cerebellar and cerebello-cerebral morphological and functional connectivity in MS and NMOSD, and further explored the association between the connectivity alterations and gene expression profiles. Results Despite numerous common alterations in the two conditions, diagnosis-specific increases in cerebellar morphological connectivity were found in MS within the cerebellar secondary motor module, and in NMOSD between cerebellar primary motor module and cerebral motor- and sensory-related areas. Both diseases also exhibited decreased functional connectivity between cerebellar motor modules and cerebral association cortices with MS-specific decreases within cerebellar secondary motor module and NMOSD-specific decreases between cerebellar motor modules and cerebral limbic and default-mode regions. Transcriptional data explained > 37.5% variance of the cerebellar functional alterations in MS with the most correlated genes enriched in signaling and ion transport-related processes and preferentially located in excitatory and inhibitory neurons. For NMOSD, similar results were found but with the most correlated genes also preferentially located in astrocytes and microglia. Finally, we showed that cerebellar connectivity can help distinguish the three groups from each other with morphological connectivity as predominant features for differentiating the patients from controls while functional connectivity for discriminating the two diseases. Conclusions We demonstrate convergent and divergent cerebellar connectome alterations and associated transcriptomic signatures between MS and NMOSD, providing insight into shared and unique neurobiological mechanisms underlying these two diseases.

ObjectiveTo evaluate the clinical significance of deep learning-derived brain age prediction in neuromyelitis optica spectrum disorder (NMOSD) relative to relapsing-remitting multiple sclerosis (RRMS).MethodsThis cohort study used data retrospectively collected from 6 tertiary neurological centres in China between 2009 and 2018. In total, 199 patients with NMOSD and 200 patients with RRMS were studied alongside 269 healthy controls. Clinical follow-up was available in 85 patients with NMOSD and 124 patients with RRMS (mean duration NMOSD=5.8±1.9 (1.9–9.9) years, RRMS=5.2±1.7 (1.5–9.2) years). Deep learning was used to learn ‘brain age’ from MRI scans in the healthy controls and estimate the brain age gap (BAG) in patients.ResultsA significantly higher BAG was found in the NMOSD (5.4±8.2 years) and RRMS (13.0±14.7 years) groups compared with healthy controls. A higher baseline disability score and advanced brain volume loss were associated with increased BAG in both patient groups. A longer disease duration was associated with increased BAG in RRMS. BAG significantly predicted Expanded Disability Status Scale worsening in patients with NMOSD and RRMS.ConclusionsThere is a clear BAG in NMOSD, although smaller than in RRMS. The BAG is a clinically relevant MRI marker in NMOSD and RRMS.

Background and purpose: Subtyping relapsing–remitting multiple sclerosis (RRMS) patients may help predict disease progression and triage patients for treatment. We aimed to subtype RRMS patients by structural MRI and investigate their clinical significances. Methods: 155 relapse-remitting MS (RRMS) and 210 healthy controls (HC) were retrospectively enrolled with structural 3DT1, diffusion tensor imaging (DTI) and resting-state functional MRI. Z scores of cortical and deep gray matter volumes (CGMV and DGMV) and white matter fractional anisotropy (WM-FA) in RRMS patients were calculated based on means and standard deviations of HC. We defined RRMS as “normal” (− 2 < z scores of both GMV and WM-FA), DGM (z scores of DGMV < − 2), and DGM-plus types (z scores of DGMV and [CGMV or WM-FA] < − 2) according to combinations of z scores compared to HC. Expanded disability status scale (EDSS), cognitive and functional MRI measurements, and conversion rate to secondary progressive MS (SPMS) at 5-year follow-up were compared between subtypes. Results: 77 (49.7%) patients were “normal” type, 37 (23.9%) patients were DGM type and 34 (21.9%) patients were DGM-plus type. 7 (4.5%) patients who were not categorized into the above types were excluded. DGM-plus type had the highest EDSS. Both DGM and DGM-plus types had more severe cognitive impairment than “normal” type. Only DGM-plus type showed decreased functional MRI measures compared to HC. A higher conversion ratio to SPMS in DGM-plus type (55%) was identified compared to “normal” type (14%, p < 0.001) and DGM type (20%, p = 0.005). Conclusion: Three MRI-subtypes of RRMS were identified with distinct clinical and imaging features and different prognosis.

Context Modified BuShenYiQi formula (M-BYF) is derived from BuShenYiQi formula, used for the treatment of allergic asthma. The exact effect and mechanism of M-BYF on the improvement of asthma remain unclear. Objective We investigated the mechanism underlying the therapeutic effect of M-BYF on allergic asthma. Materials and methods The asthma model was established in female BALB/c mice that were sensitized and challenged with ovalbumin (OVA). Mice in the treated groups were orally treated once a day with M-BYF (7, 14 and 28 g/kg/d) or dexamethasone before OVA challenge. Control and Model group received saline. Pathophysiological abnormalities and percentages of lung type 2 innate lymphoid cells (ILC2s) and Th9 cells were measured. Expression levels of type 2 cytokines and transcription factors required for these cells function and differentiation were analysed. Expression of vasoactive intestinal polypeptide (VIP)–VPAC2 signalling pathway-related proteins, and percentages of VIP expressing (VIP+) cells and VPAC2, CD90 co-expressing (VPAC2+CD90+) cells were detected. Results M-BYF alleviated airway hyperresponsiveness, inflammation, mucus hypersecretion and collagen deposition in asthmatic mice. M-BYF down-regulated percentages of ILC2s and Th9 cells with lower expression of GATA3, PU.1 and IRF4, reduced IL-5, IL-13, IL-9 and VIP production. The decrease in the expression of VIP–VPAC2 signalling pathway and percentages of VIP+ cells, VPAC2+CD90+ cells were observed after M-BYF treatment. The LD50 value of M-BYF was higher than 90 g/kg. Discussion and conclusions M-BYF alleviated experimental asthma by negatively regulating ILC2s and Th9 cells and the VIP–VPAC2 signalling pathway. These findings provide the theoretical basis for future research of M-BYF in asthma patient population.

Yixiu Pei,1,2 Yong Zhang,3 Yanyan Zhu,1,2 Yanlin Zhao,1,2 Fuqing Zhou,1,2 Muhua Huang,1,2 Lin Wu,1,2 Honghan Gong1,2 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang 330006, People’s Republic of China; 2Neuroradiology Laboratory, Jiangxi Province Medical Imaging Research Institute, Nanchang 330006, People’s Republic of China; 3Department of Pain Clinic, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province 330006, People’s Republic of ChinaCorrespondence: Fuqing ZhouDepartment of Radiology, The First Affiliated Hospital, Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi 330006, People’s Republic of ChinaTel +86 791 8869 5132Email fq.chou@yahoo.comObjective: To investigate the functional connectivity (FC) and its variability in the primary somatosensory cortex (S1) of patients with low-back-related leg pain (LBLP) in the context of the persistent stimuli of pain and numbness.Patients and Methods: We performed functional magnetic resonance imaging on LBLP patients (n = 26) and healthy controls (HCs; n = 34) at rest. We quantified and compared static FC (sFC) using a seed-based analysis strategy, with 6 predefined bilateral paired spherical regions of interest (ROIs) in the S1 cortex. Then, we captured the dynamic FC using sliding window correlation of ROIs in both the LBLP patients and HCs. Furthermore, we performed a correlational analysis between altered static and dynamic FC and clinical measures in LBLP patients.Results: Compared with controls, the LBLP patients had 1) significantly increased static FC between the left S1back (the representation of the back in the S1) and right superior and middle frontal gyrus (SFG/MFG), between the left S1chest and right SFG/MFG, between right S1chest and right SFG/MFG, between the left S1face and right MFG, and between the right S1face and right inferior parietal lobule (P < 0.001, Gaussian random field theory correction); 2) increased dynamic FC only between the right S1finger and the left precentral and postcentral gyrus and between the right S1hand and the right precentral and postcentral gyrus (P < 0.01, Gaussian random field theory correction); and 3) a negative correlation between the Barthel index and the increased static FC between the left S1face and right inferior parietal lobule (P = 0.048).Conclusion: The present study demonstrated the hyperconnectivity of the S1 cortex to the default mode and executive control network in a spatial pattern and an increase in the tendency for signal variability in the internal network connections of the S1 cortex in patients with LBLP.Keywords: primary somatosensory cortex, static functional connectivity, dynamic functional connectivity, chronic low-back-related leg pain, chronic pain, resting-state functional MRI

Background: Hippocampal involvement may differ between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Objective: To investigate the morphometric, diffusion and functional alterations in hippocampus in MS and NMOSD and the clinical significance. Methods: A total of 752 participants including 236 MS, 236 NMOSD and 280 healthy controls (HC) were included in this retrospective multi-center study. The hippocampus and subfield volumes, fractional anisotropy (FA) and mean diffusivity (MD), amplitude of low frequency fluctuation (ALFF) and degree centrality (DC) were analyzed, and their associations with clinical variables were investigated. Results: The hippocampus showed significantly lower volume, FA and greater MD in MS compared to NMOSD and HC ( p < 0.05), while no abnormal ALFF or DC was identified in any group. Hippocampal subfields were affected in both diseases, though subiculum, presubiculum and fimbria showed significantly lower volume only in MS ( p < 0.05). Significant correlations between diffusion alterations, several subfield volumes and clinical variables were observed in both diseases, especially in MS ( R = −0.444 to 0.498, p < 0.05). FA and MD showed fair discriminative power between MS and HC, NMOSD and HC (AUC > 0.7). Conclusions: Hippocampal atrophy and diffusion abnormalities were identified in MS and NMOSD, partly explaining how clinical disability and cognitive impairment are differentially affected.

Neuroimaging studies have suggested a link between the intensity of chronic low back pain intensity and structural and functional brain alterations. However, chronic pain results from the coordination and dynamics among several brain networks that comprise the dynamic pain connectome. Here, we use resting-state functional magnetic resonance imaging and measures of static (sFC) and dynamic functional connectivity (dFC) variability in the typical (0.01–0.1 Hz) and five specific (slow-6 to slow-2) frequency bands to test hypotheses regarding disruption in this variability in low back-related leg pain (LBLP) patients who experience chronic pain and numbness. Twenty-four LBLP patients and 23 healthy controls completed clinical assessments, and partial correlational analyses between altered sFC and dFC variability and clinical measures were conducted. We found a lower within-network sFC in the ascending nociceptive pathway (Asc) and a lower cross-network sFC between nodes of the salience network and the Asc in the typical frequency band. In the slow-5 frequency band, a lower within-network sFC was found in the Asc. Abnormal cross-network sFC was found between nodes of the salience network-Asc (slow-5 and slow-6) and the default mode network-Asc (slow-4 and slow-6). Furthermore, cross-network abnormalities in the typical and certain specific frequency bands were linked to clinical assessments. These findings indicate that frequency-related within- and cross-network communication among the nodes in the dynamic pain connectome is dysfunctional in LBLP patients and that selecting specific frequencies may be potentially useful for detecting LBLP-related brain activity.

Yong Zhang,1 Yanyan Zhu,2,3 Yixiu Pei,2,3 Yanlin Zhao,2,3 Fuqing Zhou,2,3 Muhua Huang,2,3 Lin Wu,2,3 Daying Zhang,1 Honghan Gong2,31Department of Pain Clinic, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province 330006, People’s Republic of China; 2Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang 330006, People’s Republic of China; 3Neuroradiology Lab, Jiangxi Province Medical Imaging Research Institute, Nanchang 330006, People’s Republic of ChinaCorrespondence: Fuqing ZhouDepartment of Radiology, The First Affiliated Hospital, Nanchang University, 17 Yongwaizheng Street,Nanchang, Jiangxi 330006, People’s Republic of ChinaTel +86 7 918 869 5132Email fq.chou@yahoo.comDaying ZhangDepartment of Pain Clinic, The First Affiliated Hospital, Nanchang University, 17 Yongwaizheng Street,Nanchang, Jiangxi 330006, People’s Republic of ChinaTel +86 7 918 869 3825Email dyzsino@ncu.edu.cnObjective: Chronic low back pain has been observed to decrease movement coordination. However, it is unclear whether the existing alteration of inter-hemispheric synchrony of intrinsic activity in patients with chronic low back-related leg pain (cLBLP). The present study aims to investigate the alteration of homotopic connectivity and its clinical association with the cLBLP patients.Participants and methods: A cohort of cLBLP patients (n=25) and well-matched healthy controls (HCs) (n=27) were recruited and underwent MRI scanning and a battery of clinical tests. The voxel-mirrored homotopic connectivity (VMHC) was used to analyze the interhemispheric coordination in the typical (0.01–0.1Hz) as well as five specific (slow-6 to slow-2) frequency bands and associated with clinical index in cLBLP patients.Results: We observed that cLBLP patients with lower homotopic connectivity than HCs in the inferior temporal gyrus, the superior temporal gyrus, the basal ganglia, the middle frontal gyrus, and the medial prefrontal cortex in the typical and five specific frequency bands, respectively. In the typical and five specific frequency bands, significant positive correlations were observed between the VMHC values of medial prefrontal cortex and the visual analogue scale scores, while the VMHC values of basal ganglia negative correlated with the values of two-point tactile discrimination (2PD) test for the right hand in cLBLP patients, etc. Further receiver operating characteristic curve analysis revealed that VMHC in the above regions with decreased could be used to differentiate the cerebral functional plasticity of cLBLP from healthy individuals with high sensitivity and specificity.Conclusion: Our results imply that multiscale frequency-related interhemispheric disconnectivity may underlie the central pathogenesis of functional coordination in patients with cLBLP.Keywords: interhemispheric integration, voxel-mirrored homotopic connectivity, chronic low back-related leg pain, chronic pain, resting-state fMRI

Using time-variant of blood oxygenation level dependent (BOLD) signal to investigate the temporal changes in functional connectivity (FC) between key nodes may shed light on the dynamic characteristics of network. Twenty-two relapsing-remitting multiple sclerosis (RRMS) and 22 well-matched healthy control subjects (HCs) participated in this study. Previously validated key nodes of attention network seeds were defined as spherical regions of interests (ROIs); then, we captured the pattern of dFC using sliding window correlation of ROIs in the RRMS and HCs during rest. Furthermore, correlation analysis between altered dFC of paired-ROIs with clinical measures in RRMS were performed. Compared with the HCs, the RRMS showed: a certain specificity transient pattern of FC of attention network at time window levels, including decreased dFC within dorsal attention network [connections of left intraparietal sulcus (LIPS)-right intraparietal sulcus (RIPS), LIPS-right frontal eye field (RFEF) and left frontal eye field (LFEF)-RIPS] and ventral attention network [connection of right ventral frontal cortex (RVFC)-right temporal parietal junction (RTPJ)], increased dFC between dorsal and ventral attention network (connections of LIPS-RTPJ and LIPS-RVFC). Secondary analysis indicated that the dFC coefficients of the connections of LIPS-RIPS (r = −0.467, P = 0.023) and RVFC-RTPJ (r = −0.452, P = 0.043) were significant negative correlated with the total white matter lesion load. In conclusion, we found that the instantaneous configuration pattern of FC in attention network of RRMS are relate to lesions loads.

Understanding the central mechanisms responsible for lumbar nerve root compression may facilitate the development of new therapeutic strategies. In this study, our aim was to investigate the amplitude of fluctuations (AF) in five specific frequency bands and the full-frequency band realm to provide novel insight into the rhythm of the neuronal activity of low back/leg pain (LBLP) patients (n = 25). Compared with healthy controls, LBLP patients exhibited a significantly altered AF in multiple brain regions, including the right or left middle and inferior temporal gyri, bilateral precuneus, right anterior insula/frontal operculum, right or left inferior parietal lobule/postcentral gyrus, and other locations at five specific frequencies (P 0.01, with Gaussian random field theory correction). Trends of an increase and a decrease in the AF in pain- and sensory-related regions, respectively, were also observed from low to high frequencies (Bonferroni-corrected α level of P 0.05/84). In addition, in the bilateral rectal gyrus, a significant association was identified between the AF in the five specific frequency bands and disease status (P

Introduction Previous neuroimaging studies have suggested that brain functional impairment and hyperarousal occur during the daytime among patients with chronic insomnia disorder (CID); however, alterations to the brain's intrinsic functional architecture and their association with sleep quality have not yet been documented. Methods In this study, our aim was to investigate the insomnia‐related alterations to the intrinsic connectome in patients with CID (n = 27) at resting state, with a data‐driven approach based on graph theory assessment and functional connectivity density (FCD), which can be interpreted as short‐range (intraregional) or long‐range (interregional) mapping. Results Compared with healthy controls with good sleep, CID patients showed significantly decreased long‐range FCD in the dorsolateral prefrontal cortices and the putamen. These patients also showed decreased short‐range FCD in their multimodal‐processing regions, executive control network, and supplementary motor‐related areas. Furthermore, several regions showed increased short‐range FCD in patients with CID, implying hyper‐homogeneity of local activity. Conclusions Together, these findings suggest that insufficient sleep during chronic insomnia widely affects cortical functional activities, including disrupted FCD and increased short‐range FCD, which is associated with poor sleep quality., Using graph theory assessment and functional connectivity density (FCD) methods to investigate the insomnia‐related alterations to the intrinsic connectome in patients with CID patients, we found that insufficient sleep during chronic insomnia widely affects cortical functional activities, including disrupted FCD and increased short‐range FCD, which is associated with poor sleep quality.

Subtyping relapsing-remitting multiple sclerosis (RRMS) patients may help predict disease progression and triage patients for treatment. We aimed to subtype RRMS patients by structural MRI and investigate their clinical significances.155 relapse-remitting MS (RRMS) and 210 healthy controls (HC) were retrospectively enrolled with structural 3DT1, diffusion tensor imaging (DTI) and resting-state functional MRI. Z scores of cortical and deep gray matter volumes (CGMV and DGMV) and white matter fractional anisotropy (WM-FA) in RRMS patients were calculated based on means and standard deviations of HC. We defined RRMS as "normal" (- 2 z scores of both GMV and WM-FA), DGM (z scores of DGMV - 2), and DGM-plus types (z scores of DGMV and [CGMV or WM-FA] - 2) according to combinations of z scores compared to HC. Expanded disability status scale (EDSS), cognitive and functional MRI measurements, and conversion rate to secondary progressive MS (SPMS) at 5-year follow-up were compared between subtypes.77 (49.7%) patients were "normal" type, 37 (23.9%) patients were DGM type and 34 (21.9%) patients were DGM-plus type. 7 (4.5%) patients who were not categorized into the above types were excluded. DGM-plus type had the highest EDSS. Both DGM and DGM-plus types had more severe cognitive impairment than "normal" type. Only DGM-plus type showed decreased functional MRI measures compared to HC. A higher conversion ratio to SPMS in DGM-plus type (55%) was identified compared to "normal" type (14%, p 0.001) and DGM type (20%, p = 0.005).Three MRI-subtypes of RRMS were identified with distinct clinical and imaging features and different prognosis.

CD4+T helper (Th) cells are important mediators of immune responses in asthma and cancer. When counteracted by different classes of pathogens, naïve CD4+T cells undergo programmed differentiation into distinct types of Th cells. Th cells orchestrate antigen-specific immune responses upon their clonal T-cell receptor (TCR) interaction with the appropriate peptide antigen presented on MHC class II molecules expressed by antigen-presenting cells (APCs). T helper 9 (Th9) cells and regulatory T (Treg) cells and their corresponding cytokines have critical roles in tumor and allergic immunity. In the context of asthma and cancer, the dynamic internal microenvironment, along with chronic inflammatory stimuli, influences development, differentiation, and function of Th9 cells and Treg cells. Furthermore, the dysregulation of the balance between Th9 cells and Treg cells might trigger aberrant immune responses, resulting in development and exacerbation of asthma and cancer. In this review, the development, differentiation, and function of Th9 cells and Treg cells, which are synergistically regulated by various factors including cytokine signals, transcriptional factors (TFs), costimulatory signals, microenvironment cues, metabolic pathways, and different signal pathways, will be discussed. In addition, we focus on the recent progress that has helped to achieve a better understanding of the roles of Th9 cells and Treg cells in allergic airway inflammation and tumor immunity. We also discuss how various factors moderate their responses in asthma and cancer. Finally, we summarize the recent findings regarding potential mechanisms for regulating the balance between Th9 and Treg cells in asthma and cancer. These advances provide opportunities for novel therapeutic strategies that are aimed at reestablishing the balance of these cells in the diseases.

Purpose To investigate the brain MRI features in neuromyelitis optica spectrum disorders (NMOSD) and its clinical relevance in a large multi-center cohort in China. Methods 270 NMOSD patients were recruited from seven centers. The brain MRI were classified as normal, NMOSD-specific lesions, multiple sclerosis-like, nonspecific white matter changes. Brain volumes including whole brain, white, gray matter, cortex and subcortex gray matter volume were measured. The relationship between MRI measures, clinical disability and cognitive impairment were investigated. Results 98 patients (36.3%) had normal brain MRI; 48 patients (17.7%) had NMOSD-specific lesions located in dorsal brainstem, corticospinal tract corpus, callosum and periependymal lesions surrounding the ventricular system; 16 patients (6%) had multiple sclerosis-like lesions; and 108 patients (40%) had nonspecific white matter changes. NMOSD patients with brain lesions had a trend of lower subcortex gray matter volume compared to patients without lesions. 52.5% patients with normal brain MRI and 50.8% patients with abnormal brain MRI showed cognitive impairment. No significant differences were identified in brain volume between cognitive impairment and cognitive preserved groups. Conclusion In this large multicenter NMOSD cohort, nonspecific white matter changes were the most common findings (40%). NMOSD patients with brain lesions demonstrated a trend of having lower brain volume than patients without lesions. Approximately 50% NMOSD patients presented cognitive impairment independent of brain lesions.

Background Although previous studies have shown that intra-network abnormalities in brain functional networks are correlated with clinical/cognitive impairment in multiple sclerosis (MS), there is little information regarding the pattern of causal interactions among cognition-related resting-state networks (RSNs) in different disease stages of relapsing–remitting MS (RRMS) patients. We hypothesized that abnormalities of causal interactions among RSNs occurred in RRMS patients in the acute and remitting phases. Methods Seventeen patients in the acute phases of RRMS, 24 patients in the remitting phases of RRMS, and 23 appropriately matched healthy controls participated in this study. First, we used group independent component analysis to extract the time courses of the spatially independent components from all the subjects. Then, the Granger causality analysis was used to investigate the causal relationships among RSNs in the spectral domain and to identify correlations with clinical indices. Results Compared with the patients in the acute phase of RRMS, patients in the remitting phase of RRMS showed a significantly lower expanded disability status scale, modified fatigue impact scale scores, and significantly higher paced auditory serial addition test (PASAT) scores. Compared with healthy subjects, during the acute phase, RRMS patients had significantly increased driving connectivity from the right executive control network (rECN) to the anterior salience network (aSN), and the causal coefficient was negatively correlated with the PASAT score. During the remitting phase, RRMS patients had significantly increased driving connectivity from the rECN to the aSN and from the rECN to the visuospatial network. Conclusions Together with the disease duration (mean disease duration

Allergic asthma is a common airway inflammatory disease and mainly caused by abnormal immune responses to allergens and viruses. The precise mechanisms of airway inflammation and airway hyper-responsiveness (AHR) are still not completely understood. CD4 + helper T cells (Th cells) serve as critical regulators of allergic immunity. The imbalance between T helper 9 (Th9) cells and forkhead box protein 3 (Foxp3) + regulatory T (Treg) cells may contribute to airway inflammation in asthma. Epimedin C, a dominant compound isolated from Herba Epimedii , has shown anti-inflammatory effects and the immunoregulatory activity, such as increase of lymphocyte proliferation. However, the protective role of epimedin C in an experimental model of ovalbumin (OVA)-induced allergic airway inflammation and the underlying mechanism remain unknown. Female BALB/c mice were sensitized by intraperitoneal injection (i.p.) of OVA plus aluminum hydroxide (Alum) and subsequently challenged with an aerosol of 3% OVA in saline. Mice were treated with different concentrations of epimedin C (20 mg/kg/d, 40 mg/kg/d, 80 mg/kg/d) for 4 weeks. Experimental endpoints were evaluated via the analysis of AHR to acetyl-β-methacholine (Mch), differential inflammatory cell counts, concentrations of cytokines interleukin-9 (IL-9), IL-4 and IL-10 in bronchoalveolar lavage fluid (BALF), serum OVA-specific IgE level, as well as airway inflammation, mucus secretion and collagen deposition in mice. Mechanistically, we investigated the percentages of Th9 cells and Treg cells, as well as mRNA levels of IL-9 and transcription factor Foxp3 in lungs. Furthermore, the proteins expression of nuclear factor-κB (NF-κB) family members p105/p50, RelA, p100/p52 and RelB, as well as mitogen-activated protein kinase (MAPK) family members extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 MAPK was detected. Epimedin C dose-dependently attenuated AHR, airway inflammation, mucus hypersecretion and collagen deposition in OVA-induced murine asthma model. The expression levels of IL-9, IL-4 and OVA-specific IgE were significantly decreased while IL-10 was increased by epimedin C. We further confirmed that epimedin C decreased the percentage of lung Th9 cells with lower mRNA expression of IL-9 and increased the percentage of lung Treg cells with higher mRNA expression of Foxp3. In addition, epimedin C dose-dependently decreased the protein levels of p52, RelB, phosphorylation of ERK1/2 and p38 MAPK which are pivotal to the development of Th9 cells and Treg cells. Collectively, epimedin C could inhibit pathophysiological features of asthma by reconstruction of the balance between Th9 cells and Treg cells through regulation of the noncanonical NF-κB p52/RelB pathway and MAPKs activation. These findings suggest epimedin C as a potential remedy for inflammatory airway diseases .

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The initial deposition kinetics of colloidal MnO2 on three representative surfaces in aquatic systems (i.e., silica, magnetite, and alumina) in NaNO3 solution were investigated in the presence of model constituents, including humic acid (HA), a polysaccharide (alginate), and a protein (bovine serum albumin (BSA), using laboratory quartz crystal microbalance with dissipation monitoring equipment (QCM-D). The results indicated that the deposition behaviors of MnO2 colloids on three surfaces were in good agreement with classical Derjaguin–Landau–Verwey–Overbeek (DLVO) theory. Critical deposition concentrations (CDC) were determined to be 15.5 mM NaNO3 and 9.0 mM NaNO3 when colloidal MnO2 was deposited onto silica and magnetite, respectively. Both HA and alginate could largely retard the deposition of MnO2 colloids onto three selected surfaces due to steric repulsion, and HA was more effective in decreasing the deposition rate relative to alginate. However, the presence of BSA can provide more attractive depo...

Fuqing Zhou,1,2 Lili Gu,3 Shunda Hong,1,2 Jiaqi Liu,1,2 Jian Jiang,1,2 Muhua Huang,1,2 Yong Zhang,3 Honghan Gong1,2 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Neuroradiology Laboratory, Jiangxi Province Medical Imaging Research Institute, Nanchang, Jiangxi, People’s Republic of China; 3Department of Pain Clinic, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China Objective: The aim of this study was to explore the amplitude of intrinsic low-frequency oscillations (LFOs) in patients with discogenic low-back and leg pain (LBLP).Participants and methods: We obtained and compared the LFO amplitude from 25 right-handed discogenic LBLP patients (13 males; mean age 55.16±1.83years) and 27 well-matched healthy controls (15 males; mean age 52.96±1.63years). The LFO amplitude was examined using the voxel-wise amplitude of low-frequency fluctuations (ALFFs), and partial correlation analysis was performed to determine the relationship between the regions with altered ALFF values and clinical parameters in discogenic LBLP patients.Results: Compared with healthy controls, the patients with discogenic LBLP showed a significant increase in ALFF in the affective system of the pain matrix (left anterior cingulate cortex, right anterior insula/frontal operculum, and bilateral orbitofrontal cortex) and information-processing regions (middle occipital/temporal gyrus). In addition, a significant decrease in ALFF was observed in the default mode network (DMN; inferior parietal lobule (IPL) and medial prefrontal cortex [mPFC]) and the processing system of the pain matrix (basal ganglia/thalamus/midbrain, postcentral gyrus [PoCG], and fusiform gyrus). Several regions with altered ALFF were associated with disease duration, visual analog scale scores, Barthel index, and fine sensory modality measurements (two-point tactile discrimination of the left and/or right leg). Further operating characteristic curves analysis suggested that the mean ALFF values in the right IPL, left IPL/PoCG, left anterior cingulate cortex, and left mPFC could serve as markers to separate individuals with discogenic LBLP from healthy subjects.Conclusion: Our results revealed widespread abnormalities in ALFF in the pain matrix and information-processing regions as well as a decrease in ALFF in the DMN. These results open up an important new avenue to better understand the nature of the link between intrinsic activity and peripheral pain and sensory impairment in discogenic LBLP patients. Keywords: amplitude of low-frequency fluctuations, resting state functional magnetic resonance imaging, discogenic low-back and leg pain, amplitude of low-frequency fluctuations

Suhua Huang,1 Fuqing Zhou,2,3 Jian Jiang,2,3 Muhua Huang,2,3 Xianjun Zeng,2,3 Shan Ding,1 Honghan Gong2,3 1Department of Radiology, Jiangxi Province Children’s Hospital, 2Department of Radiology, The First Affiliated Hospital, Nanchang University, 3Jiangxi Province Medical Imaging Research Institute, Nanchang, People’s Republic of China Abstract: Several neuroimaging studies have suggested that brain impairment and plasticity occur in patients with chronic primary insomnia (CPI); however, the effects of insomnia on the intrinsic organization of the brain remain largely unknown. In this study, a voxel-based functional connectivity strength (FCS) assessment, a data-driven method based on a theoretical approach, was applied to investigate the effects of insomnia on the intrinsic organization of the whole brain in 27 treatment-naïve CPI patients and 26 well-matched healthy controls (HCs). Compared with HCs, CPI patients exhibited decreased FCS primarily in the right dorsolateral prefrontal cortex, the right medial prefrontal cortex (MPFC), the left basal ganglia/insula, and the right cerebellum anterior lobe (CAL) due to decreased functional connectivity patterns. These results suggest that poor sleep quality could impair FCS within the brain, including the MPFC and the CAL, which are important for cognitive control and modulating motor and limbic functions. Additionally, a receiver operator characteristic analysis revealed that altered FCS has moderate sensitivity (76.9%–88.5%) and specificity (59.3%–70.4%) as a reference indicator to discriminate CPI patients from HCs. Taken together, these findings provide evidence for abnormal intrinsic brain activity in CPI patients and might improve our understanding of the pathophysiological processes that occur in insomnia patients. Keywords: functional connectivity strength, disconnection, chronic primary insomnia, sleep disorders, resting-state fMRI

Using Kendall's coefficient of concordance (KCC-) and Coherence (Cohe-) regional homogeneity (ReHo) to explore the alterations of brain local functional connectivity in acute and remitting relapsing-remitting multiple sclerosis (RRMS), and its clinical relevance. 18 acute RRMS, 26 remitting RRMS and 20 healthy controls received resting-state functional magnetic resonance imaging scanning. After data preprocessing and ReHo (KCC-ReHo and Cohe-ReHo) calculation, analysis of variance and followed post hoc analysis was used to compare the KCC-ReHo or Cohe ReHo maps across groups. After analysis of variance analysis, regions with significant among-group differences detected by the 2 ReHo analysis were overlapped, these overlapped regions located in the left superior frontal gyrus (SFG), right SFG, left cuneus and right middle occipital gyrus (P

Muhua Huang,1,2 Fuqing Zhou,1,2 Lin Wu,1,2 Bo Wang,1,2 Hui Wan,3 Fangjun Li,3 Xianjun Zeng,1,2 Honghan Gong1,2 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, People’s Republic of China; 2Neuroradiology Laboratory, Jiangxi Province Medical Imaging Research Institute, Nanchang, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital, Nanchang University, Nanchang, People’s Republic of China Background and purpose: The effects of the interactions between the default mode network (DMN) and the dorsal attention network (DAN), which present anticorrelated behaviors, in relapsing-remitting multiple sclerosis (RRMS) are poorly understood. This study used resting-state functional connectivity (FC) and the Granger causality test (GCT) to examine changes in the undirected and effective functional network connectivity (FNC) between the two networks during the remitting phase in RRMS patients.Patients and methods: Thirty-three patients experiencing a clinically diagnosed remitting phase of RRMS and 33 well-matched healthy control subjects participated in this study. First, an independent component (IC) analysis was performed to preprocess the functional magnetic resonance imaging data and select resting-state networks. Then, an FNC analysis and the GCT were combined to examine the temporal correlations between the ICs of the DMN and DAN and to identify correlations with clinical markers.Results: Compared with the healthy subjects, the RRMS patients in the remitting phase showed the following: 1) significantly decreased FC within the DAN in the postcentral gyrus and decreased FC within the DMN in several regions except the parahippocampal gyrus, where increased FC was observed; 2) a relatively stable interaction between the two anticorrelated networks as well as a driving connectivity from the DAN to DMN (IC15); and 3) significantly positive correlations between the connectivity coefficient of the right superior temporal gyrus and the Modified Fatigue Impact Scale score (ρ = 0.379, p = 0.036).Conclusion: Adaptive mechanisms that maintain stable interactions might occur between the DMN and DAN during the remitting phase in RRMS patients. Keywords: default mode network, dorsal attention network, multiple sclerosis, resting-state functional MRI, Granger causality test, anticorrelation

Shunda Hong,1,* Lili Gu,2,* Fuqing Zhou,1 Jiaqi Liu,1 Muhua Huang,1 Jian Jiang,1 Laichang He,1 Honghan Gong,1 Xianjun Zeng1 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Pain, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People’s Republic of China *These authors contributed equally to this work Purpose: The aim of this study was to explore intrinsic functional connectivity patterns in patients with herpes zoster (HZ) and postherpetic neuralgia (PHN). Patients and methods: Thirty-three right-handed HZ patients (13 males; mean age 57.15±9.30 years), 22 right-handed PHN patients (9 males; mean age 66.13±6.77 years), and 28 well-matched healthy controls (HC) (9 males; mean age 54.21±7.72 years) underwent resting-state functional magnetic resonance imaging for intrinsic functional connectivity analyses. Functional connectivity density (FCD) was calculated and compared among the PHN, HZ, and HC groups. In addition, the Pearson correlation coefficient was calculated to compare various clinical indices in the regions with abnormal FCD values. Results: Compared with the HC, both HZ and PHN patients showed significantly decreased FCD in the precuneus, and patients with HZ displayed significantly increased FCD in the brainstem/limbic lobe/parahippocampalgyrus, whereas patients with PHN displayed significantly increased FCD in the hippocampus (correlation thresholds r=0.25, voxel level of P

Fuqing Zhou,1,2 Muhua Huang,1,2 Lin Wu,1,2 Yongming Tan,1,2 Jianqiang Guo,1,2 Yong Zhang,3 Laichang He,1,2 Honghan Gong1,2 1Department of Radiology, the First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China; 2Jiangxi Province Medical Imaging Research Institute, Nanchang, Jiangxi Province, People’s Republic of China; 3Department of Pain Clinic, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China Objective: Advanced magnetic resonance imaging studies have shown functional plasticity or reorganization and metabolite alterations of N-acetyl aspartate in the sensorimotor cortex (SMC), a hallmark region and key brain network, in patients with cervical spondylotic myelopathy (CSM). However, the nature of perfusion in the SMC and the relationship between regional cerebral blood flow (CBF), motor function scores, and structural damage of the cervical cord in patients with CSM are not fully understood.Materials and methods: All right-handed participants underwent pseudo-continuous arterial spin labeling pulse sequence scanning, and CBF was then calculated and compared between CSM and healthy groups. Clinical and structural associations were assessed in the SMC. Receiver operating characteristic (ROC) and leave-one-out cross-validation analyses were used to estimate the sensitivity and specificity of the significantly altered CBF in the SMC to distinguish myelopathy-related impairment.Results: A total of 18 pairs of CSM patients and well-matched healthy subjects were included in the analyses. Compared with healthy subjects, CSM patients exhibited significantly decreased CBF in the left premotor ventral/precentral operculum (PMv/PrCO) and the bilateral dorsal anterior cingulate cortex (dACC); and increased CBF in the left paracentral lobule (PCL), the right PCL/supplementary motor area (PCL/SMA), and the right postcentral gyrus (PoCG; Gaussian random field correction at P

A new nano-composite energetic material, in which submicrometer ammonium perchlorate (AP) particles and nanoparticles of cyclotrimethylene trinitramine (RDX) were uniformly dispersed in the cross-linked nitrocellulose (NC), was prepared by the sol–gel method. The structure of the material was confirmed by means of SEM, XRD and N2 adsorption isotherm techniques, and the results showed that the NC/RDX/AP nano-composite energetic material is monolithic with numerous pores of nanometer scale and the mean grain size of RDX is

The classical concept that amyotrophic lateral sclerosis (ALS) is a degenerative disorder characterized by the loss of upper and lower motor neurons is agreed. However, more and more studies have suggested the involvement of some extra-motor regions. The aim of this study is to investigate the frequency-related alteration pattern of intrinsic functional connectivity strength (FCS) at the voxel-wise level in the relatively early-stage of ALS on a whole brain scale. In this study, 21 patients with ALS and 21 well-matched healthy control subjects were enrolled to examine the intrinsic FCS in the different frequencies (slow-4: 0.027-0.073 Hz; slow-5: 0.01-0.027 Hz, and typical band: 0.01-0.1 Hz). Compared with the control subjects, the ALS patients showed a significantly decreased FCS in the left prefrontal cortex (PFC) and the bilateral superior frontal gyrus. In the slow-5 band, the patients with ALS showed decreased FCS in the left lingual gyrus, as well as increased FCS in the left postcentral gyrus/paracentral lobule (PoCG/PARC). In the slow-4 band, the ALS patients presented decreased FCS in the left and right ventrolateral PFC. Moreover, the increased FCS in the left PoCG/PARC in the slow-5 band was positively correlated with the ALSFRS-r score (P = 0.015). Our results demonstrated that the FCS changes in ALS were wide spread and frequency dependent. These findings may provide some evidences that ALS patients have the consistent impairment in some extra-motor regions at a relatively early-stage.

Background and purpose: Previous voxel-based morphometry (VBM) studies have suggested that cortical atrophy is regionally distributed in middle-aged subjects with white matter hyperintense (WMH) lesions. However, few studies have assessed cortical thickness in middle-aged WMH subjects. In this study, we examined cortical thickness as well as cortical morphometry associated with the presence of WMH lesion load in middle-aged subjects.Participants and methods: Thirty-six middle-aged subjects with WMH lesions (WMH group) and without clinical cognitive impairment, and 34 demographically matched healthy control subjects (HCS group) participated in the study. Cortical thickness was estimated using an automated Computational Anatomy Toolbox (CAT12) as the distance between the gray-white matter border and the pial surface. Individual WMH lesions were manually segmented, and WMH loads were measured. Statistical cortical maps were created to estimate differences in cortical thickness between groups based on this cortex-wide analysis. The relationship between WMH lesion loads and cerebral cortical thickness was also analyzed in CAT12.Results: Cortical thickness was significantly lower in the WMH group than in the controls in multimodal integration regions, including the right and left dorsal anterior cingulate cortex (dACC), right and left frontal operculum (fO), right and left operculum parietale (OP), right and left middle temporal gyrus (MTG), and left superior temporal gyrus (STG; P < 0.01, family-wise error (FWE)-corrected). Additionally, cortical thickness was also lower in the recognition regions that contained the right temporal pole (TP), the right and left fusiform gyrus, and the left rolandic operculum (RO; P < 0.01, FWE-corrected). The results revealed that in the left superior parietal lobule (SPL), cortical thickness was higher in the WMH group than in the HCS group (P < 0.01, FWE-corrected). A voxel-wise negative correlation was found between cortical thickness and WMH lesion loads in the right orbitofrontal cortex (OFC), right dorsolateral prefrontal cortex (DLPFC), and right subcallosal cortex (P < 0.01, FWE-corrected).Conclusion: The main findings of this study suggest that middle-aged WMH subjects are more likely to exhibit cortical thinning, especially in multimodal integration and recognition- and motor-related regions. The current morphometry data provide further evidence for WMH-associated structural plasticity.

Previous neuroimaging studies have shown that functional changes occur after acute sleep deprivation, which suggest detrimental effects of a lack of sleep on the intrinsic functional architecture of the brain. We aimed to identify regional resting perfusion changes in subjects with acute sleep deprivation. Thirty-three healthy subjects with habitual good sleep participated in 36 hours (2 days and 1 night) of sleep deprivation and then underwent the attention network test and pseudo-continuous arterial spin labeling scanning. Regional cerebral blood flow was used to compare cerebral perfusion before and after sleep deprivation. Correlation analyses of regional perfusion changes and scores on the attention network test were performed. Compared with the baseline (n = 20) scans, the scans of subjects after sleep deprivation (n = 26) revealed a slower response time (549.99 milliseconds vs 603.36 milliseconds; t = −2.301; P = .028) and a significantly higher lapse rate (0.88% vs 22.85%; t = −2.977; P = .006). The sleep deprivation subjects showed lower cerebral blood flow (CBF) in the left parahippocampal gyrus/fusiform cortex (pHipp/Fus), right pHipp/Fus, and right prefrontal cortex (PFC) relative to the baseline subjects (Gaussian random field correction, voxel level P

A novel phosphorus−nitrogen flame retardant, octahydro-2,7-di(N,N-dimethylamino)-1,6,3,8,2,7-dioxadiazadiphosphecine (ODDP), with bi-phosphonyl in a cyclic compound, was synthesized by the reaction of POCl3, NH(CH3)2·HCl with OHCH2CH2NH2 in CH2Cl2 solution, and characterized by Fourier transform infrared spectrometer, nuclear magnetic resonance, and mass spectrum. ODDP has been successfully reacted with polyurethane (PU) as a chain extender to prepare phosphorus–nitrogen synergistic halogen-free flame-retardant waterborne PU (DPWPU). Limiting oxygen index (LOI), UL-94, thermogravimetric analysis and scanning electron microscopy suggest the excellent flame retardancy of the DPWPU polymer. When the content of ODDP was 15 wt %, the LOI of DPWPU was 30.6% and UL-94 achieved a V-0 classification. Compared with the unmodified WPU, the thermodecomposition temperature of the DPWPU was reduced and the amount of carbon residue was increased to 18.18%. The surface of carbon residue was shown to be compact and smooth without holes, which would be favorable for resisting oxygen and heat. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41288.