Injectable Nano-in-Gel Vaccine for Spatial and Temporal Control of Vaccine Kinetics and Breast Cancer Postsurgical Therapy.

Breast cancer is the most commonly diagnosed cancer, and surgical resection is the first choice for its treatment. With the development of operation techniques, surgical treatment for breast cancer is evolving toward minimally invasive and breast-conserving approaches. However, breast-conserving surgery is prone to an increased risk of cancer recurrence and is becoming a key challenge that needs to be solved. In this study, we introduce a one-shot injectable nano-in-gel vaccine (NIGel-Vax) for postoperative breast cancer therapy. The NIGel-Vax was constructed by mixing protein antigens with PEI-4BImi-Man adjuvant and then encapsulated in a hydrogel made with oxidized dextran (ODEX) and 4-arm PEG-ONH2. Using 4T1 tumor-extracted proteins as antigen, the NIGel-Vax achieved a 92% tumor suppression rate and a 33% cure rate as a postoperative therapy in the 4T1 tumor model. Using the tumor-associated antigen trophoblast cell-surface antigen 2 (TROP2) protein as the antigen, NIGel-Vax achieved a 96% tumor suppression rate and a 50% cure rate in triple-negative breast cancer (TNBC) models. This design provides an encouraging approach for breast cancer postoperative management.

Paget disease of the breast with underlying invasive ductal cancer in neurofibromatosis type 1: a case report.

Background: Neurofibromatoses (NFs) are a group of rare autosomal dominant genetic disorders characterized by tumors growing in the nervous system. Neurofibromas, which are soft noncancerous tumors, have been found on or under the skin in patients with NF1. Furthermore, patients with NF1 are susceptible to various cancers, including breast cancer. Neurofibromas under the skin of the breast can delay the diagnosis of breast cancer, which severely reduces life expectancy. Paget disease of the breast (PDB) is a rare type of breast cancer that causes eczema-like changes of the nipple. Case Description: Here, we present a rare case of a 50-year-old woman who was diagnosed with NF1 and an invasive ductal breast carcinoma accompanied by PDB. The patient underwent mastectomy, sentinel lymph node biopsy, and adjuvant therapies, including chemotherapy, anti-human epidermal growth factor receptor 2 (HER2) therapy, and endocrine therapy. No local recurrence or distance metastasis was found at 3 years of follow-up. Conclusions: NF1 patients aged <50 years have a higher risk of breast cancer and a worse prognosis. Moreover, neurofibroma in the breast can easily mask signs of breast cancers. Therefore, early breast cancer screening is crucial for patients with NF1. Radiotherapy should be avoided because of potential carcinogenicity to the neurofibromas. Mastectomy, and not breast-conserving surgery, is the optimal choice. Patients should undergo regular postoperative follow-up so that contralateral breast cancer can be detected early.

Causal Structural Covariance Network Suggesting Structural Alterations Progression in Type 2 Diabetes Patients.

Background and Purpose: According to reports, type 2 diabetes (T2D) is a progressive disease. However, no known research has examined the progressive brain structural changes associated with T2D. The purpose of this study was to determine whether T2D patients exhibit progressive brain structural alterations and, if so, how the alterations progress. Materials and Methods: Structural magnetic resonance imaging scans were collected for 81 T2D patients and 48 sex-and age-matched healthy controls (HCs). Voxel-based morphometry (VBM) and causal structural covariance network (CaSCN) analyses were applied to investigate gray matter volume (GMV) alterations and the likely chronological processes underlying them in T2D. Two sample t-tests were performed to compare group differences, and the differences were corrected using Gaussian random field (GRF) correction (voxel-level p < 0.001, cluster-level p < 0.01). Results: Our findings demonstrated that GMV alterations progressed in T2D patients as disease duration increased. In the early stages of the disease, the right temporal pole of T2D patients had GMV atrophy. As the diseases duration prolonged, the limbic system, cerebellum, subcortical structures, parietal cortex, frontal cortex, and occipital cortex progressively exhibited GMV alterations. The patients also exhibited a GMV alterations sequence exerting from the right temporal pole to the limbic-cerebellum-striatal-cortical network areas. Conclusion: Our results indicate that the progressive GMV alterations of T2D patients manifested a limbic-cerebellum-striatal-cortical sequence. These findings may contribute to a better understanding of the progression and an improvement of current diagnosis and intervention strategies for T2D.

Evaluation of altered brain activity in type 2 diabetes using various indices of brain function: A resting-state functional magnetic resonance imaging study.

Background: Type 2 diabetes mellitus (T2DM) has been identified as a risk factor that increases the rate of cognitive decline. Previous studies showed that patients with T2DM had brain function alterations based on a single index of resting-state functional magnetic resonance imaging (rs-fMRI). The present study aimed to explore spontaneous brain activity in patients with T2DM by comparing various rs-fMRI indices, and to determine the relationship between these changes and cognitive dysfunction. Methods: A total of 52 patients with T2DM and age- and sex-matched control participants were included in this study. The amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and voxel-mirrored homotopic connectivity (VMHC) values were calculated to represent the status of spontaneous neural activity. The Montreal Cognitive Assessment (MoCA) was used for the rapid evaluation of cognition in all subjects. Pearson correlation and mediation analyses were conducted to investigate the relationship between rs-fMRI indices and clinical parameters such as fasting glucose, disease duration, and MoCA. Results: Patients with T2DM had alterations of concordant spontaneous brain activity in brain areas including the bilateral cerebellum posterior lobe, the left inferior temporal gyrus (ITG.L), the parahippocampal gyrus, and the left supplementary motor area (SMA.L). The indices were significantly correlated to each other in most of the detected brain areas. Positive correlations were observed between fasting glucose and neural activity in the surrounding areas of the left insula and the inferior frontal gyrus. MoCA scores were negatively correlated with the ReHo values extracted from the left anterior occipital lobe and the superior cerebellar cortex and were positively correlated with VMHC values extracted from the left caudate and the precentral gyrus (PreCG). No significant mediation effect of abnormal brain activity was found in the relationship between clinical parameters and MoCA scores. Conclusion: The current study demonstrated the functional concordance of abnormal brain activities in patients with T2DM by comparing ALFF, ReHo, and VMHC measurements. Widespread abnormalities mainly involved in motor and sensory processing functions may provide insight into examining T2DM-related neurological pathophysiology.

lncRNA MELTF-AS1 facilitates osteosarcoma metastasis by modulating MMP14 expression.

Osteosarcoma is a highly aggressive cancer common in children and adolescents. There is still a lack of effective treatments for metastatic or recurrent osteosarcoma. The role of long non-coding RNAs (lncRNAs) in osteosarcoma has gradually attracted attention. Here, we identified lncRNAs that were abnormally expressed in metastatic osteosarcoma through analyzing the sequencing data of osteosarcoma tissues and selected upregulated lncRNA MELTF-AS1 for detailed study. The qRT-PCR analysis showed that the expression of MELTF-AS1 was increased in osteosarcoma tissues and cells, and the high expression of MELTF-AS1 indicated a poor prognosis of osteosarcoma patients. The high expression of MELTF-AS1 in osteosarcoma was partly due to the transcriptional activation of RREB1. The results of transwell assays, scratch wound healing assays, and the tail vein injection lung metastasis model demonstrated that knocking down MELTF-AS1 inhibited metastasis ability of osteosarcoma cells. Furthermore, the results of RNA pull-down assays, luciferase reporter assays, and RNA immunoprecipitation (RIP) assays revealed that MELTF-AS1 could regulate MMP14 expression through interaction with miR-485-5p. Our study suggested that MELTF-AS1 functioned as a pro-metastasis gene in osteosarcoma by upregulating MMP14 and that it could be a potential therapeutic and diagnostic target for osteosarcoma.

Study of Diffusion Weighted Imaging Derived Diffusion Parameters as Biomarkers for the Microenvironment in Gliomas.

OBJECTIVES: To explore the efficacy of diffusion weighted imaging (DWI)-derived metrics under different models as surrogate indicators for molecular biomarkers and tumor microenvironment in gliomas. METHODS: A retrospective study was performed for 41 patients with gliomas. The standard apparent diffusion coefficient (ADCst) and ADC under ultra-high b values (ADCuh) (b values: 2500 to 5000 s/mm2) were calculated based on monoexponential model. The fraction of fast diffusion (f), pseudo ADC (ADCfast) and true ADC (ADCslow) were calculated by bi-exponential model (b values: 0 to 2000 s/mm2). The apparent diffusional kurtosis (Kapp) was derived from the simplified diffusion kurtosis imaging (DKI) model (b values: 200 to 3000 s/mm2). Potential correlations between DWI parameters and immunohistological indices (i.e. Aquaporin (AQP)1, AQP4, AQP9 and Ki-67) were investigated and DWI parameters were compared between high- and low-grade gliomas, and between tumor center and peritumor. Receiver operator characteristic (ROC) curve and area under the curve (AUC) were calculated to determine the performance of independent or combined DWI parameters in grading gliomas. RESULTS: The ADCslow and ADCuh at tumor center showed a stronger correlation with Ki-67 than other DWI metrics. The ADCst, ADCslow and ADCuh at tumor center presented correlations with AQP1 and AQP4 while AQP9 did not correlate with any DWI metric. Kapp showed a correlation with Ki-67 while no significant correlation with AQPs. ADCst (p < 0.001) and ADCslow (p = 0.001) were significantly lower while the ADCuh (p = 0.006) and Kapp (p = 0.005) were significantly higher in the high-grade than in the low-grade gliomas. ADCst, f, ADCfast, ADCslow, ADCuh, Kapp at the tumor center had significant differences with those in peritumor when the gliomas grade became high (p < 0.05). Involving ADCuh and Kapp simultaneously into an independent ADCst model (AUC = 0.833) could further improve the grading performance (ADCst+ADCuh+Kapp: AUC = 0.923). CONCLUSION: Different DWI metrics fitted within different b-value ranges (low to ultra-high b values) have different efficacies as a surrogate indicator for molecular expression or microstructural complexity in gliomas. Further studies are needed to better explain the biological meanings of these DWI parameters in gliomas.

A huge malignant phyllodes tumor of the breast with osteoclast-like giant cells: a case report.

The malignant phyllodes tumor (PT) of the breasts is a rare type of fibroepithelial neoplasm. Osteoclast-like giant cells (OLGCs) exist in many types of tumors. But malignant PTs with OLGCs were rarely reported. Here, we presented a case of a 49-year-old woman who had a 23 cm ×21 cm ×6 cm mass which was growing for 2 years in her left breast. The patient had moderate anemia due to the hemorrhage and exudation on the surface of the tumor. The imaging examinations such as PET-CT found no lymphatic involvement and distant metastasis. We performed mastectomy with a 2 cm surgical margin and free skin flap transplantation to restore the big wound. The vacuum assisted closure (VAC) system was used to promote wound healing. Histological examination of the surgical specimen showed atypical spindle-like stroma cells, marked nuclear pleomorphism, focal necrosis, and mitotic activity. Typical leaf-like architectures of PTs were observed in some regions. OLGCs were found in many sections of the tumor with a number of vascular proliferations. The final diagnosis was malignant PT with OLGCs. After a three-month follow-up, no local recurrence or metastasis was found. Autogenous skin grafts with VAC are available for large area skin defect after excising a huge breast tumor. The presence of OLGCs in malignant tumors may be related to necrosis and hemorrhage of the tumor. These findings also provide opportunities for understanding the mechanisms of tumor formation and development.

Ferroptosis inducer erastin downregulates androgen receptor and its splice variants in castration­resistant prostate cancer.

To date, there is no effective therapy available for the treatment of castration­resistant prostate cancer (CRPC), and patients generally succumb to the disease within 2 to 4 years. In the progression of CRPC, androgen receptor (AR) and its splice variants play critical roles. Hence, it is necessary to develop a drug to inhibit the expression and activity of the full­length and splice variants of AR for the treatment of CRPC. Erastin, as the first discovered drug to induce ferroptosis, has been studied in various types of cancer. However, there are few studies focusing on the relationship between erastin and AR. In the present study, western blotting, and sulforhodamine B cell viability, glutathione, lipid peroxidation and reactive oxygen species assays were performed to verify the ferroptosis of CRPC cells; reverse transcription­quantitative polymerase chain reaction, dual­luciferase reporter, and lentiviral packaging and lentivirus­infected cell assays were employed to evaluate how erastin affects AR. A mouse xenograft assay was used to determine the underlying mechanism in vivo. Erastin, as a classical inducer of ferroptosis, can suppress the transcriptional activities of both the full­length and splice variants in AR models in vitro and in vivo. In addition, when erastin was used for CRPC treatment combined with docetaxel, the growth inhibitory efficacy of docetaxel was found to be enhanced. Thus, these findings indicated that ferroptosis inducer erastin has potential in the treatment of CRPC via targeting AR.

Evaluation of Glypican-3 Expression in Hepatocellular Carcinoma by Using IDEAL IQ Magnetic Resonance Imaging.

RATIONALE AND OBJECTIVES: To investigate the value of iterative decomposition of water and fat with echo asymmetry and least squares estimation (IDEAL IQ) and gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for evaluating Glypican-3 (GPC3) expression in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Seventy-six patients with histopathologic diagnosis of HCC were retrospectively included in this study. In all patients IDEAL IQ and Gd-EOB-DTPA-enhanced MRI were performed preoperatively using a 3 T MRI system. For an identical slice through the liver of each patient a region of interest was drawn on the tumor in the hepatobiliary phase image and copied to the R2* map and fat fraction map produced by IDEAL IQ. A Mann-Whitney U test was used to compare the region of interest values of R2*, fat fraction and uptake of Gd-EOB-DTPA values between patients with positive and negative GPC3 expression HCC. Receiver operating characteristic analysis was used to determine the diagnostic performances of each of the MRI parameters in evaluating GPC3 expression and histological grade in HCC. RESULTS: R2* value was significantly higher in cases of positive than negative GPC3 expression HCCs (p < 0.001), whereas there were no significant differences in fat fraction and uptake of Gd-EOB-DTPA between the 2 groups (both p > 0.05). R2* value had higher areas under receiver operating characteristic (0.881), sensitivity (85.96%), and specificity (84.21%) compared to the fat fraction and uptake of Gd-EOB-DTPA. CONCLUSION: R2* value yielded from IDEAL IQ could reliably predict GPC3 expression in HCC prior to surgery.

Altered Effective Connectivity of Bilateral Hippocampus in Type 2 Diabetes Mellitus.

Patients with type 2 diabetes mellitus (T2DM) experience cognitive deficits but the underlying pathophysiologic mechanisms are not known. We therefore applied Granger causality analysis of resting-state functional magnetic resonance imaging to study the effective connectivity (EC) of the hippocampus in patients with T2DM. Eighty six patients with T2DM and 84 matched healthy controls (HC) were recruited. The directional EC between anatomically defined seeds in left hippocampus (LHIP) and right hippocampus (RHIP) and other brain regions was compared between T2DM and HC and Pearson correlation analysis was performed to determine whether alterations in EC were related to clinical characteristics of diabetes. Compared with HC, patients with T2DM had altered EC between LHIP and RHIP and the default mode network (DMN), occipital cortex and cerebellum. In addition, for LHIP only duration of diabetes positively correlated with decreased inflow from right postcentral gyrus and right parietal lobe, glycosylated hemoglobin (HbA1c) negatively correlated with decreased inflow from right thalamus (r = -0.255, p = 0.018) and Montreal Cognitive Assessment (MoCA) negatively correlated with decreased inflow from left inferior parietal lobe (r = -0.206, p = 0.05). The altered EC between hippocampus and DMN is interpreted to be related to cognitive deficits in patients with T2DM particularly affecting memory and learning.

Real-time near-infrared fluorescence imaging mediated by blue dye in breast cancer patients.

BACKGROUND: Near-infrared (NIR) fluorescence imaging has recently been introduced to the sentinel lymph node (SLN) mapping because of the benefits of the SLN biopsy, such as providing real-time and high-resolution optical guidance. Methylene blue is available and less expensive as an SLN mapping tracer. Our study aims to identify SLN through the NIR fluorescence imaging system mediated by blue dye. METHODS: Early-stage breast cancer patients were prospectively enrolled. All participants received a subareolar or peritumoral injection of 1 mL methylene blue (MB) before surgery. The MB fluorescence system was set immediately after injection. SLNs were searched and removed under the guidance of fluorescence and blue dye. RESULTS: We identified SLN adequately with the help of real-time lymphography and blue dye. Symbolic lymphatic drainage patterns were also observed. CONCLUSION: NIR fluorescence imaging mediated by blue dye has benefits on the identification of lymph vessels, the location of SLN, and the patterns of breast lymphatic flow.

The myodural bridge complex defined as a new functional structure.

PURPOSE: The connective tissue between suboccipital muscles and the cervical spinal dura mater (SDM) is known as the myodural bridge (MDB). However, the adjacent relationship of the different connective tissue fibers that form the MDB remains unclear. This information will be highly useful in exploring the function of the MDB. METHODS: The adjacent relationship of different connective tissue fibers of MDB was demonstrated based upon three-dimensional visualization model, P45 plastinated slices and histological sections of human MDB. RESULTS: We found that the MDB originating from the rectus capitis posterior minor muscle (RCPmi), rectus capitis posterior major muscle (RCPma) and obliquus capitis inferior muscle (OCI) in the suboccipital region coexists. Part of the MDB fibers originate from the ventral aspect of the RCPmi and, together with that from the cranial segment of the RCPma, pass through the posterior atlanto-occipital interspace (PAOiS) and enter into the posterior aspect of the upper cervical SDM. Also, part of the MDB fibers originate from the dorsal aspect of the RCPmi, the ventral aspect of the caudal segment of the RCPma, and the ventral aspect of the medial segment of the OCI, enter the central part of the posterior atlanto-axial interspace (PAAiS) and fuse with the vertebral dura ligament (VDL), which connects with the cervical SDM. CONCLUSIONS: Our findings prove that the MDB exists as a complex structure which we termed the 'myodural bridge complex' (MDBC). In the process of head movement, tensile forces could be transferred possibly and effectively by means of the MDBC. The concept of MDBC will be beneficial in the overall exploration of the function of the MDB.

Identification of Cognitive Dysfunction in Patients with T2DM Using Whole Brain Functional Connectivity.

Majority of type 2 diabetes mellitus (T2DM) patients are highly susceptible to several forms of cognitive impairments, particularly dementia. However, the underlying neural mechanism of these cognitive impairments remains unclear. We aimed to investigate the correlation between whole brain resting state functional connections (RSFCs) and the cognitive status in 95 patients with T2DM. We constructed an elastic net model to estimate the Montreal Cognitive Assessment (MoCA) scores, which served as an index of the cognitive status of the patients, and to select the RSFCs for further prediction. Subsequently, we utilized a machine learning technique to evaluate the discriminative ability of the connectivity pattern associated with the selected RSFCs. The estimated and chronological MoCA scores were significantly correlated with R = 0.81 and the mean absolute error (MAE) = 1.20. Additionally, cognitive impairments of patients with T2DM can be identified using the RSFC pattern with classification accuracy of 90.54% and the area under the receiver operating characteristic (ROC) curve (AUC) of 0.9737. This connectivity pattern not only included the connections between regions within the default mode network (DMN), but also the functional connectivity between the task-positive networks and the DMN, as well as those within the task-positive networks. The results suggest that an RSFC pattern could be regarded as a potential biomarker to identify the cognitive status of patients with T2DM.

Altered Resting-State Functional Activity in Medication-Naive Patients With First-Episode Major Depression Disorder vs. Healthy Control: A Quantitative Meta-Analysis.

Background: There is an urgent need for a meta-analysis that characterizes the brain states of major depression disorder (MDD) patients and potentially provides reliable biomarkers, because heterogeneity in the results of resting-state functional neuroimaging has been observed between studies, with some patients not showing the consistent changes, or even opposite patterns. Thus, we evaluated consistent regional brain activity alterations in medication-naive patients with first-episode unipolar MDD and compared the results with those in healthy controls (HCs). Methods: A systematic database search was conducted (in PubMed, Ovid, and Web of Knowledge) between January 1984 and July 2016 to select resting-state functional activity studies with a voxel-wise analysis in MDD. We used anisotropic effect size-signed differential mapping to perform a whole-brain meta-analysis, comparing functional alterations between first-episode medication-naive unipolar MDD patients and HCs by integrating the studies. In addition, subgroup meta-analysis was conducted to control for the MRI analysis method. Moreover, the meta-regression analyses were performed to examine the potential effects of mean age, education duration, illness duration, and severity of depressive symptoms. Results: A total of 12 studies were included, comparing 313 MDD patients with 283 HCs. The pooled and subgroup meta-analysis found that the MDD patients showed hyperactivity in the left parahippocampal gyrus, left supplementary motor area, left amygdala, left hippocampus, and left middle frontal gyrus (MFG; orbital part), and hypoactivity in the left lingual gyrus, left middle occipital gyrus, right cuneus cortex, right MFG (orbital part), and left cerebellum. In the meta-regression analyses, the mean illness duration was positively associated with hyper-activation in the left parahippocampal gyrus and hypoactivation in the hemispheric lobule IV/V of the left cerebellum. Conclusions: This meta-analysis indicated that MDD patients had significant and robust resting-state brain activity alteration in amygdala, left hippocampus and other regions, which implicated this finding in the pathophysiology of cognitive and emotional impairment in MDD patients.

Brain Functional Networks in Type 2 Diabetes Mellitus Patients: A Resting-State Functional MRI Study.

BACKGROUND: Previous diabetes mellitus studies of cognitive impairments in the early stages have focused on changes in brain structure and function, and more recently the focus has shifted to the relationships between encephalic regions and diversification of network topology. However, studies examining network topology in diabetic brain function are still limited. METHODS: The study included 102 subjects; 55 type 2 diabetes mellitus (T2DM) patients plus 47 healthy controls. All subjects were examined by resting-state functional magnetic resonance imaging (rs-fMRI) scan. According to Automated Anatomical Labeling, the brain was divided into 90 anatomical regions, and every region corresponds to a brain network analysis node. The whole brain functional network was constructed by thresholding the correlation matrices of the 90 brain regions, and the topological properties of the network were computed based on graph theory. Then, the topological properties of the network were compared between different groups by using a non-parametric test. Finally, the associations between differences in topological properties and the clinical indicators were analyzed. RESULTS: The brain functional networks of both T2DM patients and healthy controls were found to possess small-world characteristics, i.e., normalized clustering coefficient (γ) > 1, and normalized characteristic path length (λ) close to 1. No significant differences were found in the small-world characteristics (σ). Second, the T2DM patient group displayed significant differences in node properties in certain brain regions. Correlative analytic results showed that the node degree of the right inferior temporal gyrus (ITG) and the node efficiencies of the right ITG and superior temporal gyrus of T2DM patients were positively correlated with body mass index. CONCLUSION: The brain network of T2DM patients has the same small-world characteristics as normal people, but the normalized clustering coefficient is higher and the normalized characteristic path length is lower than that of the normal control group, indicating that the brain function network of the T2DM patients has changed. The changes of node properties were mostly concentrated in frontal lobe, temporal lobe and posterior cingulate gyrus. The abnormal changes in these indices in T2DM patients might be explained as a compensatory behavior to reduce cognitive impairments, which is achieved by mobilizing additional neural resources, such as the excessive activation of the network and the efficient networking of multiple brain regions.

Altered Resting-State Functional Activity in Patients With Autism Spectrum Disorder: A Quantitative Meta-Analysis.

Background: There is accumulating evidence showing that patients with autism spectrum disorder (ASD) have obvious changes in resting-state functional brain activity. So far, there have been no meta-analyses of the resting-state brain activity alterations in patients with ASD. We attempted to explore the resting-state functional activity changes in patients with ASD, possibly providing a new perspective for investigating the pathophysiology of patients with ASD. Methods: We screened relevant studies published before August 2017 in PubMed, Ovid, Web of Science, China National Knowledge Infrastructure (CNKI), and the Wan-fang database. Fifteen resting-state functional neural activity datasets (including 382 patients and 348 healthy controls) were included. Through the use of the effect-size signed differential mapping (ES-SDM) method, we carried out a meta-analysis of resting-state functional activity studies of patients with ASD. Results: Compared with healthy controls, patients with ASD showed hyperactivity in the right supplementary motor area, middle frontal gyrus, inferior frontal gyrus, the left precentral gyrus, and the bilateral cerebellum hemispheric lobule (VIII/IX), and hypoactivity in the right middle temporal gyrus, superior temporal gyrus, and the left precuneus, posterior cingulate cortex, median cingulate cortex, and bilateral cerebellum (crus I). Conclusion: This meta-analysis indicates that patients with ASD have significant and robust resting-state brain activity alterations in the language comprehension network, inferior-posterior cerebellum, default mode network (DMN), and cerebellar crus I. These brain regions may serve as specific regions of interest for further studies of ASD, which will allow us to further clarify the neurobiological mechanisms in patients with ASD.

Orientation and property of fibers of the myodural bridge in humans.

BACKGROUND CONTEXT: Studies over the past 20 years have revealed that there are fibrous connective tissues between the suboccipital muscles, nuchal ligament, and cervical spinal dura mater (SDM). This fibrous connection with the SDM is through the posterior atlanto-occipital or atlantoaxial interspaces and is called the myodural bridge (MDB). Researchers have inferred that the MDB might have important functions. It was speculated that the function of MDB might be related to proprioception transmission, keeping the subarachnoid space and the cerebellomedullary cistern unobstructed, and affecting the dynamic circulation of the cerebrospinal fluid. In addition, clinicians have found that the pathologic change of the MDB might cause cervicogenic or chronic tension-type headache. Previous gross anatomical and histologic studies only confirmed the existence of the MDB but did not reveal the fiber properties of the MDB. This is important to further mechanical and functional research on the MDB. PURPOSE: Multiple histologic staining methods were used in the present study to reveal the various origin and fiber properties of the MDB. Muscles and ligaments participating in forming the MDB at the posterior atlanto-occipital or atlantoaxial interspaces were observed, and the fiber properties of the MDB were confirmed. The present study provides a basis for speculating the tensile force values of the MDB on the SDM and a morphologic foundational work for exploring the physiological functions and clinical significances of the MDB. STUDY DESIGN: Anatomical and histologic analyses of suboccipital structures that communicate with the SDM at the posterior atlanto-occipital or atlantoaxial interspaces were carried out. METHODS: Multiple histologic staining methods were used to evaluate the histologic properties and composition of the MDB at the posterior atlanto-occipital or atlantoaxial interspaces in five formalin-fixed head-neck human specimens. RESULTS: The results show that the MDB traversing the atlanto-occipital interspace originated from the rectus capitis posterior minor (RCPmi). The MDB traversing the atlantoaxial interspace originated mainly from the RCPmi, rectus capitis posterior major, and obliquus capitis inferior. These fibers form the vertebral dural ligament in the atlantoaxial interspace and connect with SDM. The MDB is mainly formed by parallel running type I collagen fibers; thus, suboccipital muscle could pull SDM strongly through the effective force propagated by the MDB during head movement. CONCLUSIONS: Myodural bridge is mainly formed by parallel running type I collagen fibers; thus, it can transmit the strong pull from the diverse suboccipital muscles or ligaments during head movement. The results of the present study will serve as a basis for further biomechanical and functional MDB research.

Reduced Gray Matter Volume in Patients with Type 2 Diabetes Mellitus.

Background and Purpose: Previous studies of voxel-based morphometry (VBM) have found that patients with type 2 diabetes mellitus (T2DM) exhibit gray matter alterations, but these findings are inconsistent and have not been quantitatively reviewed. Therefore, the aim of this study was to conduct a quantitative meta-analysis of VBM studies of patients with T2DM. Materials and Methods: The seed-based d mapping method was applied to quantitatively estimate the regional gray matter abnormalities in T2DM patients. We also used meta-regression to explore the effects of some demographics and clinical characteristics. Results: Seven studies, with 8 datasets comprising 530 participants with T2DM and 549 non-T2DM controls, were included. The pooled and subgroup meta-analyses found that T2DM patients showed robustly reduced gray matter in the bilateral superior temporal gyrus, middle temporal gyrus, medial superior frontal gyrus, insula, median cingulate cortex, precuneus cortex and the left lentiform nucleus extending into the parahippocampus. The meta-regression also found that the percentage of female patients with T2DM was negatively associated with gray matter in the right superior temporal gyrus and illness duration was negatively associated with gray matter in the right middle temporal gyrus. Conclusion: This meta-analysis indicates that T2DM patients have significantly and robustly reduced gray matter mainly in the cortical-striatal-limbic networks, which are associated with human cognition. Thereby implicating this finding in the pathophysiology of cognitive impairment in T2DM patients.

Amide proton transfer magnetic resonance imaging in detecting intracranial hemorrhage at different stages: a comparative study with susceptibility weighted imaging.

Amide proton transfer (APT) imaging is a noninvasive molecular magnetic resonance imaging (MRI) technique based on the chemical exchange-dependent saturation transfer mechanism. The purpose of this study was to investigate the diagnostic performance of APT MRI in detecting intracranial hemorrhage (ICH) at hyperacute, acute and subacute stages by comparing with susceptibility weighted imaging (SWI). APT MRI and SWI were performed on 33 included patients with ICH by using a 3-T MRI unit. A two-sided Mann-Whitney U test was used to detect differences in APT-weighted (APTw) and SWI signal intensities of ICH at hyperacute, acute and subacute stages. Receiver operating characteristic analysis was used to assess the diagnostic utilities of APT MRI and SWI. Our results showed that APT MRI could detect ICH at hyperacute, acute and subacute stages. Therefore, APTw signal intensity may serve as a reliable, noninvasive imaging biomarker for detecting ICH at hyperacute, acute and subacute stages. Moreover, APT MRI could provide additional information for the ICH compared with SWI.