Differently Distributed Iron Deposition in Mild and Moderate Stroke with Small Artery Occlusion: A Pilot Voxel-Based Susceptibility Mapping Study.

BACKGROUND: Small artery occlusion (SAO) is a common ischemic stroke subtype. However, its clinical outcome can be more severe than commonly understood. The severity of SAO can vary, ranging from mild to moderate. Iron deposition has been associated with the development and progression of stroke. However, its specific distribution and relationship with stroke severity in SAO remain unclear. The study's purpose is to investigate the differences in iron deposition between mild stroke with SAO (SAO-MiS) and moderate stroke with SAO (SAO-MoS) through quantitative susceptibility mapping (QSM) and its association with neurological deficits. METHODS: Sixty-eight SAO participants within 24 hours of first onset were enrolled and separated into SAO-MiS and SAO-MoS according to the National Institutes of Health Stroke Scale (NIHSS) scores. QSM helped calculate the susceptibility maps, reflecting the iron content within the brain. The susceptibility maps were analyzed using voxel-wise statistical analysis to compare the iron deposition between SAO-MiS and SAO-MoS. Then, differentially distributed iron deposition helped differentiate between mild and moderate stroke using support vector machine (SVM) methods. RESULTS: Compared with SAO-MiS, SAO-MoS depicted elevated iron deposition in the left pallidum, parahippocampal gyrus, and superior frontal gyrus medial region, and is lower in the right superior/middle frontal gyrus and bilateral supplementary motor area. Based on iron deposition, the SVM classifier's analysis revealed a high power to discriminate SAO-MoS from SAO-MiS. In addition, fibrinogen, triglyceride (TG), and total cholesterol (TC) were linked with QSM values in specific brain regions. CONCLUSIONS: Our study first revealed the brain iron distribution after SAO and differently distributed iron deposition in SAO-MiS and SAO-MoS. The results indicate that iron deposition could play a role in the pathophysiology of SAO and its correlation with stroke severity.

A gene chip study suggests that miR-17-3p is associated with diabetic foot ulcers.

Background of the Study Diabetic foot ulcers (DFUs) are severe effect of diabetes. This research aimed to discover the role of micro-ribonucleic acid (miRNA) in treating DFUs involved in maggot debridement therapy (MDT) via a miRNA chip study. A miRNA chip approach was adopted. Patients with diabetes (type 1 or 2) who had at least one-foot ulcer (current or previous) were enrolled in the study. The alterations of miRNA expressions in the granulation tissue during treatment with MDT were measured. Following MDT, the increased expression of miR17-92 was verified in vivo. The miR-17-3p expression increased, and Flk-1 (vascular endothelial growth factor) expression was significantly reduced in patients with DFUs who received MDT (P < 0.01). Results from human umbilical vein endothelial cells that excrete or secrete showed consistency with in vitro findings (P < 0.001, P < 0.05). The overexpression of miR-17-3p demonstrated inhibitory activity on tube formation (P < 0.05). When DFUs were treated with MDT, it revealed that miR-17-3p had a negative regulatory effect on Flk-1.

Maggot debridement therapy stimulates wound healing by altering macrophage activation.

The purpose of this study is to determine the impact of maggot debridement therapy (MDT) on macrophages during the healing process of diabetic foot ulcers (DFU). The activation phenotype of macrophages during wound healing following MDT was evaluated using double staining immunohistochemistry (IHC). In addition, markers associated with macrophage activation were discovered using immunoblotting and real-time polymerase chain reaction (PCR). During the process of diabetic wound healing following MDT, the presence and over-expression of M2 macrophages were observed, while the under-expression of M1 macrophages was noted. In addition, the activation markers of macrophages exhibited a correlation with the indicated Th1/Th2 cytokines. MDT interventions have the potential to modulate macrophage activity, thereby aiding in the healing of diabetic foot wounds.

Curative effects of microneedle fractional radiofrequency system on skin laxity in Asian patients: A prospective, double-blind, randomized, controlled face-split study.

BACKGROUND: To date, no studies compared curative effects of thermal lesions in deep and superficial dermal layers in the same patient (face-split study). OBJECTIVE: To evaluate skin laxity effects of microneedle fractional radiofrequency induced thermal lesions in different dermal layers. METHODS AND MATERIALS: 13 patients underwent three sessions of a randomized face-split microneedle fractional radiofrequency system (MFRS) treatment of deep dermal and superficial dermal layer. Skin laxity changes were evaluated objectively (digital images, 2 independent experts) and subjectively (patients' satisfaction numerical rating). RESULTS: 12 of 13 subjects completed a course of 3 treatments and a 1-year follow-up. Improvement of nasolabial folds in deep dermal approach was significantly better than that in superficial approach at three months (P=.0002) and 12 months (P=.0057) follow-up. Effects on infraorbital rhytides were only slightly better (P=.3531). CONCLUSION: MFRS is an effective method to improve skin laxity. Thermal lesion approach seems to provide better outcomes when applied to deep dermal layers. It is necessary to consider the skin thickness of different facial regions when choosing the treatment depth.

Cyclophilin A as a downstream effector of PI3K/Akt signalling pathway in multiple myeloma cells.

Cyclophilin A (Cyp A), a member of the peptidyl-prolyl isomerase (PPI) family, may function as a molecular signalling switch. Comparative proteomic studies have identified Cyp A as a potential downstream target of protein kinase B (Akt). This study confirmed that Cyp A is a downstream effector of the phosphatidylinositide 3-kinase (PI3K)/Akt signalling pathway. Cyp A was highly phosphorylated in response to interleukin-6 treatment, which was consistent with the accumulation of phosphorylated Akt, suggesting that Cyp A is a phosphorylation target of Akt and downstream effector of the PI3K/Akt pathway. Cyclosporine A (CsA), a PPI inhibitor, inhibited the growth of multiple myeloma (MM) U266 cells. Moreover, CsA treatment inhibited the activation of the signal transducer and activator of transcription 3 (STAT3) in MM U266 cells. Several Cyp A mutants were generated. Mutants with mutated AKT phosphorylation sites increased the G1 phase arrest in MM U266 cells. The other mutants that mimicked the phosphorylated state of Cyp A decreased the percentage of G1 phase. These results demonstrated that the states of phosphorylation of Cyp A by Akt can influence the progress of the cell cycle in MM U266 cells and that this effect is probably mediated through the Janus-activated kinase 2/STAT3 signalling pathway.

Quantitative phosphoproteomic analysis of RIP3-dependent protein phosphorylation in the course of TNF-induced necroptosis.

Tumor necrosis factor (TNF) induced cell death in murine fibrosarcoma L929 cells is a model system in studying programed necrosis (also known as necroptosis). Receptor interacting protein 3 (RIP3), a serine-threonine kinase, is known to play an essential role in TNF-induced necroptosis; however, the phosphorylation events initiated by RIP3 activation in necroptotic process is still largely unknown. Here, we performed a quantitative MS based analysis to compare TNF-induced changes in the global phosphoproteome of wild-type (RIP3(+/+) ) and RIP3-knockdown L929 cells at different time points after TNF treatment. A total of 8058 phosphopeptides spanning 6892 phosphorylation sites in 2762 proteins were identified in the three experiments, in which cells were treated with TNF for 0.5, 2, and 4 h. By comparing the phosphorylation sites in wild-type and RIP3-knockdown L929 cells, 174, 167, and 177 distinct phosphorylation sites were revealed to be dependent on RIP3 at the 0.5, 2, and 4 h time points after TNF treatment, respectively. Notably, most of them were not detected in a previous phosphoproteomic analysis of RIP3-dependent phosphorylation in lipopolysaccharide-stimulated peritoneal macrophages and TNF-treated murine embryonic fibroblasts (MEFs), suggesting that the data presented in this report are highly relevant to the study of TNF-induced necroptosis of L929 cells.

Investigation of receptor interacting protein (RIP3)-dependent protein phosphorylation by quantitative phosphoproteomics.

Receptor interacting protein 3 (RIP3) is a protein kinase that plays a key role in programmed necrosis. Despite the importance of RIP3-dependent necrosis in many pathological processes, current knowledge on the function of RIP3 is very limited. Here we present the results of a proteome-wide analysis of RIP3-regulated phosphorylation sites using cells from wildtype (RIP3(+/+)) and RIP3 knockout (RIP3(-/-)) mice. Because the activation of RIP3 requires stimulation by certain extracellular stimuli such as ligands of death receptors or Toll-like receptors, we compared the phosphorylation sites of lipopolysaccharide (LPS)-treated peritoneal macrophages from RIP3(+/+) and RIP3(-/-) mice and the phosphorylation sites of tumor necrosis factor (TNF)-treated RIP3(+/+) and RIP3(-/-) mouse embryonic fibroblast (MEF) cells. Stable isotope labeling by amino acids in cell culture and spike-in stable isotope labeling by amino acids in cell culture were used in the analyses of the MEFs and macrophages, respectively. Proteomic analyses using stable isotope labeling by amino acids in cell culture coupled with immobilized metal affinity chromatography-hydrophilic interaction liquid chromatography fractionation and nanoLC MS/MS identified 14,057 phosphopeptides in 4306 proteins from the macrophages and 4732 phosphopeptides in 1785 proteins from the MEFs. Analysis of amino acid sequence motifs among the phosphopeptides identified a potential motif of RIP3 phosphorylation. Among the phosphopeptides identified, 73 were found exclusively in RIP3(+/+) macrophages, 121 were detected exclusively from RIP3(+/+) MEFs, 286 phosphopeptides were induced more in RIP3(+/+) macrophages than in RIP3(-/-) macrophages and 26 phosphopeptides had higher induction in RIP3(+/+) MEFs than in RIP3(-/-) cells. Many of the RIP3 regulated phosphoproteins from the macrophages and MEF cells are functionally associated with the cell cycle; the rest, however, appear to have diverse functions in that a number of metabolism related proteins were phosphorylated in macrophages and development related phosphoproteins were induced in MEFs. The results of our phosphoproteomic analysis suggest that RIP3 might function beyond necrosis and that cell type specific function of RIP3 exists.

Use of autologous iliac crest graft and free anterolateral femoral skin flap in diabetic foot ulcers: a case report.

BACKGROUND: Diabetic foot has a great impact on the life of patients. Its treatment involves a multi-disciplinary and multi-direction approach, which requires not only soft tissue repair, but also bone reconstruction and functional repair. CASE PRESENTATION: A 51-year-old Chinese man with a three-year history of diabetes was diagnosed with ulcers in his left foot. We performed a successful procedure, and the different strategies we adopted helped to avoid serious complications during treatment. The patient was treated with debridement, bone cement, iliac crest graft, and anterolateral femoral skin flap, and recovered well. CONCLUSION: There is a dearth of reports pertaining to treatment of diabetic foot in patients with midfoot bone and soft tissue loss. In this report, we present an effective method that we used to reconstruct the loss of midfoot in a patient with diabetic foot, illustrating a successful therapeutic strategy for saving limbs in this complex medical condition.

Revealing a natural marine product as a novel agonist for retinoic acid receptors with a unique binding mode and inhibitory effects on cancer cells.

Retinoids display anti-tumour activity on various cancer cells and therefore have been used as important therapeutic agents. However, adverse side effects and RA (retinoic acid) resistance limit further development and clinical application of retinoid-based therapeutic agents. We report in the present paper the identification of a natural marine product that activates RARs (RA receptors) with a chemical structure distinct from retinoids by high-throughput compound library screening. Luffariellolide was uncovered as a novel RAR agonist by inducing co-activator binding to these receptors in vitro, further inhibiting cell growth and regulating RAR target genes in various cancer cells. Structural and molecular studies unravelled a unique binding mode of this natural ligand to RARs with an unexpected covalent modification on the RAR. Functional characterization further revealed that luffariellolide displays chemotherapeutic potentials for overcoming RA resistance in colon cancer cells, suggesting that luffariellolide may represent a unique template for designing novel non-retinoid compounds with advantages over current RA drugs.

Comparison of a fractional microplasma radio frequency technology and carbon dioxide fractional laser for the treatment of atrophic acne scars: a randomized split-face clinical study.

BACKGROUND: No studies have compared fractional microplasma radio frequency (RF) technology with the carbon dioxide fractional laser system (CO2 FS) in the treatment of atrophic acne scars in the same patient. OBJECTIVE: To compare the efficacy and safety of fractional microplasma RF with CO2 FS in the treatment of atrophic acne scars. METHODS AND MATERIALS: Thirty-three Asian patients received three sessions of a randomized split-face treatment of fractional microplasma RF or CO2 FS. RESULTS: Both modalities had a roughly equivalent effect. Échelle d'Évaluation Clinique Des Cicatrices d'Acné scores were significantly lower after fractional microplasma RF (from 51.1 ± 14.2 to 22.3 ± 8.6, 56.4% improvement) and CO2 FS (from 48.8 ± 15.1 to 19.9 ± 7.9, 59.2% improvement) treatments. There was no statistically significant difference between the two therapies. Twelve subjects (36.4%) experienced postinflammatory hyperpigmentation (PIH) after 30 of 99 treatment sessions (30.3%) on the CO2 FS side and no PIH was observed on the fractional microplasma RF sides. CONCLUSION: Both modalities have good effects on treating atrophic scars. PIH was not seen with the fractional microplasma RF, which might make it a better choice for patients with darker skin.

Closed or Unclosed Mesentery? A Meta-analysis of Internal Herniation After Laparoscopic Roux-en-Y Gastric Bypass.

During the laparoscopic Roux-en-Y gastric bypass procedure, closing mesentery or not was still controversial according to preexisted studies. So, the current meta-analysis aimed to compare the outcome of closure versus non-closure of mesenteric defects in laparoscopic Roux-en-Y gastric bypass. Fifteen studies were included, enrolling 53,488 patients. Based on the outcome of analysis, regarding internal hernia, Petersen space's IH, jejunal mesenteric's IH, hospital days, and reoperation, closure of the mesentery was better than non-closure. Besides, small bowel obstruction, anastomosis ulcer, stenosis, leakage, bleeding, gastrointestinal perforation, and postoperative BMI of patients show no difference between non-closure and closure.

Changes in functional connectivity in newly diagnosed self-limited epilepsy with centrotemporal spikes and cognitive impairment: An MEG study.

PURPOSE: Our purpose was to explore the relationship between cognitive impairment and neural network changes in patients newly diagnosed with self-limited epilepsy with centrotemporal spikes (SeLECTS). METHODS: The Wechsler Intelligence Scale for Children, fourth edition was used to divide all SeLECTS patients into two groups: patients with full-scale intelligence quotient (FSIQ) below 80 that corresponded to cognitive impairment, and patients with FSIQ above 80 that corresponded to a normal cognitive function. The data on the resting state were recorded using magnetoencephalography. The properties of the networks were analyzed using graph theory (GT) analysis. RESULTS: The functional connectivity (FC) of the frontal cortex in patients with FSIQ < 80 was reduced in the 12-30 Hz frequency band, and the FC of the posterior cingulate cortex was reduced in the 80-250 and 250-500 Hz frequency bands. The GT analysis showed that patients in the FSIQ < 80 group had higher strength in the 8-12 and 12-30 Hz frequency bands than those in the healthy control and FSIQ > 80 group. However, the path length was reduced in the 80-250 Hz band, and the clustering coefficient was reduced in the 12-30, 80-250, and 250-500 Hz frequency bands. Moreover, the receiver operator characteristic analysis showed that the clustering coefficient in the 12-30 and 80-250 Hz frequency bands, as well as the path length in the 80-250 Hz frequency band possessed a good discriminative ability in distinguishing the FSIQ > 80 group. CONCLUSIONS: SeLECTS patients with cognitive impairment in the early stage of the disease developed disordered networks in cognitive-related brain regions. The clustering coefficient in the 12-30 and 80-250 Hz frequency bands as well as the path length in the 80-250 Hz frequency band might be good indicators to distinguish the cognitive impairment of SeLECTS patients at the early stage.

Maggot treatment promotes healing of diabetic foot ulcer wounds possibly by upregulating Treg levels.

PURPOSE: Through the study of regulatory T cells (Tregs), we found a possible way to promote the healing of diabetic foot ulcers (DFUs) with maggot treatment and investigated the associated mechanism. METHODS: Immunohistochemistry was used to examinetissues from DFU patients treated with or without maggot debridement therapy (MDT). The expression of the signature Treg molecule Foxp3, interleukin-10 (IL-10), transforming growth factor-beta (TGF-ß), and interferon regulatory factor 4 (IRF-4) in patients with DFU treated with or without MDT was tested by real-time PCR (RT-PCR). CD4+ T cells from mouse spleen cells were cocultured in vitro with maggot excretions/secretions (ES), and Foxp3, IL-10, TGF-ß, and IRF-4 levels were measured by RT-PCR. RESULTS: Foxp3 expression was obviously increased in DFU patients treated using MDT but less pronounced in those treated without MDT (P < 0.05). Foxp3, IL-10, TGF-ß, and IRF-4 gene expression levels were higher in DFU patients treated with MDT than in those treated without MDT. Moreover, in vitro coculture of mouse spleen cells with ESs produced results consistent with the in vivo results (P < 0.001). CONCLUSION: MDT/ESs can obviously upregulate the Treg level and may affect DFU healing in different ways, suggesting a new direction for the future treatment of DFU.

Effects of dapagliflozin in the progression of atherosclerosis in patients with type 2 diabetes: a meta-analysis of randomized controlled trials.

AIMS: At present, an increasing number of studies are trying to determine whether dapagliflozin has a significant effect on the occurrence and development of atherosclerosis in patients with type 2 diabetes mellitus (T2DM), but there is no consensus. In addition, the former meta-analyses, relying on only a few previous studies and a minimal number of research indicators, have not been able to draw sufficient conclusions simultaneously. Consequently, we conducted a meta-analysis to evaluate the effectiveness of dapagliflozin in the occurrence and development of atherosclerosis in patients with T2DM. METHODS: We searched electronic databases (PubMed, Embase, Cochrane, and Scopus) and reference lists in relevant papers for articles published in 2011-2021. We selected studies that evaluated the effects of dapagliflozin on the risk factors related to the occurrence or development of atherosclerosis in patients with T2DM. A fixed or random-effect model calculated the weighted average difference of dapagliflozin on efficacy, and the factors affecting heterogeneity were determined by Meta-regression analysis. RESULTS: Twelve randomized controlled trials (18,758 patients) were incorporated in our meta-analysis. In contrast with placebo, dapagliflozin was associated with a significantly increase in high density lipoprotein-cholesterol (HDL-C) [MD = 1.39; 95% CI (0.77, 2.01); P < 0.0001], Δflow-mediated vasodilatation (ΔFMD) [MD = 1.22; 95% CI (0.38, 2.06); P = 0.005] and estimated Glomerular Filtration Rate(eGFR) [MD = 1.94; 95% CI (1.38, 2.51); P < 0.00001]. Furthermore, dapagliflozin had a tremendous advantage in controlling triglycerides (TG) in subgroups whose baseline eGFR < 83 ml/min/1.73m2 [MD = - 10.38; 95% CI (- 13.15, - 7.60); P < 0.00001], systolic blood pressure (SBP) [MD = - 2.82; 95% CI (- 3.22, - 2.42); P < 0.00001], HbA1c, BMI, body weight and waist circumference. However, dapagliflozin has an adverse effect on increasing total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C). Besides, there were no significant changes in other indicators, including adiponectin and C-peptide immunoreactivity. CONCLUSIONS: Our pooled analysis suggested that dapagliflozin has a terrifically better influence over HDL-C, ΔFMD, and eGFR, and it concurrently had a tremendous advantage in controlling TG, SBP, DBP, HbA1c, BMI, body weight, and waist circumference, but it also harms increasing TC and LDL-C. Furthermore, this study found that the effect of dapagliflozin that decreases plasma levels of TG is only apparent in subgroups of baseline eGFR < 83 ml/min/1.73m2, while the subgroup of baseline eGFR ≥ 83 ml/min/1.73m2 does not. Finally, the above results summarize that dapagliflozin could be a therapeutic option for the progression of atherosclerosis in patients with T2DM. Systematic review registration PROSPERO CRD42021278939.

Advances in metformin for the treatment of non-alcoholic fatty liver disease in children.

INTRODUCTION: The increased economic and social burdens for NAFLD worldwide make treating such a disease a significant public health issue. Metformin, a kind of insulin sensitizer generally used to treat type 2 diabetes, has been recently found to have efficacy on children's NAFLD in various areas such as glucolipid metabolism, intestinal bacterial metabolism, oxidative stress, and anti-inflammatory response. This article aims to provide an overview of the possible mechanisms of NAFLD in children and the potential therapeutic application of metformin. AREAS COVERED: The Cochrane Library, PubMed, Scopus, and EMBASE database was systematically searched on 12 April 2022, using the keywords metformin; non-alcoholic fatty liver disease; and children to identify similar studies. An additional search for recently published research was performed in June 2020. EXPERT OPINION: Although metformin has been proved to have an excellent therapeutic effect on children's NAFLD; we can still explore its potential impacts and mechanisms from different angles, such as combined medication. At the same time, we should also pay attention to its side effects.

Phylogenetic and recombination analysis of human bocavirus 2.

BACKGROUND: Human bocavirus 2(HBoV2) and other human bocavirus species (HBoV, HBoV3, and HBoV4) have been discovered recently. But the precise phylogenetic relationships among these viruses are not clear yet. METHODS: We collected 632 diarrhea and 162 healthy children in Lanzhou, China. Using PCR, Human bocavirus (HBoV), HBoV2, HBoV3 and HBoV4 were screened. The partial genes of NS, NP1 and VP, and two nearly complete sequences of HBoV2 were obtained. RESULT: Phylogenetic analysis showed the different genes of HBoV2 strain were homogenous with different reference strains. HBoV3 may be a recombinant derived from HBoV and HBoV4. We also observed that the VP1 and VP2 region of HBoV3 is as similar to HBoV2 as to HBoV4. CONCLUSIONS: A single genetic lineage of HBoV2 is circulating in children with and without gastroenteritis in Lanzhou, China. Current evidence in this study was not enough to support recombination between HBoV2 strains, and HBoV3 may be a recombinant between HBoV and the common ancestor of HBoV2 and HBoV4.

Stretching-Tunable High-Frequency Magnetic Properties of Wrinkled CoFeB Films Grown on PDMS.

We demonstrated a convenient method via applying uniaxial tensile strains to continuously tune the high-frequency properties of flexible magnetic films. CoFeB films were magnetron sputtered onto prestretched polydimethylsiloxane (PDMS) membranes. They exhibit a self-assembled periodic wrinkling surface structure because of the large mismatch of Young's moduli between the elastomeric PDMS substrates and the metal layers. The wrinkling morphology and the residual tensile stress caused by the Poisson effect can be continuously tuned by a uniaxial stretching strain less than the growth prestrain, which consequently results in changes in high-frequency performance. The initial permeability and the ferromagnetic resonance frequency of flexible CoFeB thin films can be monotonously tuned in wide ranges of about hundreds and 1 GHz, respectively. A good repeatability over thousands of stretching-relaxing cycles has been demonstrated without any obvious reduced high-frequency properties. This flexible CoFeB films with excellent stretching-tunable high-frequency performances are promising for application in flexible and tunable microwave devices.

Cytokine storm intervention in the early stages of COVID-19 pneumonia.

Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30th, 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response.

Impaired functional connectivity of limbic system in migraine without aura.

Aberrant functional connectivity of brain networks has been demonstrated in migraine sufferers. Functional magnetic resonance imaging (fMRI) may illustrate altered connectivity in patients suffering from migraine without aura (MwoA). Here, we applied a seed-based approach based on limbic regions to investigate disrupted functional connectivity between spontaneous migraine attacks. Resting-state fMRI data were obtained from 28 migraine patients without aura and 23 well-matched healthy controls (HC). The functional connectivity of the limbic system was characterized using a seed-based whole-brain correlation method. The resulting functional connectivity measurements were assessed for correlations with other clinical features. Neuropsychological data revealed significantly increased connectivity between the limbic system (bilateral amygdala and right hippocampus) and left middle occipital gyrus (MOG), and a positive correlation was revealed between disease duration and connective intensity of the left amygdala and the ipsilateral MOG. There was decreased functional connectivity between the right amygdala and contralateral orbitofrontal cortex (OFC). In addition, resting-state fMRI showed that, compared to HC, patients without aura had significant functional connectivity consolidation between the bilateral hippocampus and cerebellum, and a negative correlation was detected between scores on the headache impact test (HIT) and connectivity intensity of the right hippocampus and bilateral cerebellum. There was decreased functional connectivity between the left hippocampus and three brain areas, encompassing the bilateral inferior parietal gyri (IPG) and contralateral supplementary motor area (SMA). There were no structural differences between the two groups. Our data suggest that migraine patients have disrupted limbic functional connectivity to pain-related regions of the modulatory and encoding cortices, which are associated with specific clinical characteristics. Disturbances of resting-state functional connectivity may play a key role in neuropathological features, perception and affection of migraine. The current study provides further insights into the complex scenario of migraine mechanisms. .