The prevalence of non-obese nonalcoholic fatty liver disease (NAFLD) is increasing worldwide with unclear etiology and pathogenesis. Here, we show GP73, a Golgi protein upregulated in livers from ...patients with a variety of liver diseases, exhibits Rab GTPase-activating protein (GAP) activity regulating ApoB export. Upon regular-diet feeding, liver-GP73-high mice display non-obese NAFLD phenotype, characterized by reduced body weight, intrahepatic lipid accumulation, and gradual insulin resistance development, none of which can be recapitulated in liver-GAP inactive GP73-high mice. Common and specific gene expression signatures associated with GP73-induced non-obese NAFLD and high-fat diet (HFD)-induced obese NAFLD are revealed. Notably, metformin inactivates the GAP activity of GP73 and alleviates GP73-induced non-obese NAFLD. GP73 is pathologically elevated in NAFLD individuals without obesity, and GP73 blockade improves whole-body metabolism in non-obese NAFLD mouse model. These findings reveal a pathophysiological role of GP73 in triggering non-obese NAFLD and may offer an opportunity for clinical intervention.
To investigate the magnetic resonance imaging (MRI) features of orbital Langerhans cell histiocytosis (LCH) to improve diagnostic accuracy.
We retrospectively reviewed clinical manifestations and MRI ...findings of 23 patients with histopathology-confirmed LCH of the orbit. The findings were evaluated for the following: (a) symptoms, (b) disease duration, (c) location, (d) configuration, (e) margin, (f) MR imaging signal intensity and enhanced performance.
Eighteen patients (78%) in our series were male, only five (22%) patients were female, and the mean age at presentation was 6.3 years. The common symptoms include swollen eyelids, exophthalmos, and a palpable mass. Fourteen patients presented with swollen eyelids and/or exophthalmos. Twenty-two cases involved unilateral orbits, and one case involved bilateral orbits. In our study, there was one patient with cough and expectoration, and one patient with polydipsia and polyuria. Lesions were located in the superior or superlateral orbital roof of seventeen patients (74%). Lesions formed masses or irregular shapes. The 12 out of 23 (52.2%) cases appeared heterogeneous isointense and 10 out of 23 (43.5%) cases showed iso-hypointense on T1-weighted imaging, there were 15 out of 23 (65.2%) cases showed hyper-hypointense mixed signals on T2-weighted imaging. 7 cases found patchy hyperintense signal on T1WI, and 11 cases showed markedly hyperintense signal near the edge of lesions on T2WI. After enhancement, 21 out of 23 (91.3%) cases lesions presented marked enhancement at the edges and the surrounding tissues, and with heterogeneous obvious enhancement of the lesion center. Besides, four cases lesions were surrounded by a low circular signal.
There were several characteristics MRI features that can provide crucial information for clinicians and improve our understanding and the diagnostic accuracy of the orbital LCH.
It remains unclear whether very preterm (VP) infants have the same level of brain structure and function as full-term (FT) infants. In addition, the relationship between potential differences in ...brain white matter microstructure and network connectivity and specific perinatal factors has not been well characterized.
This study aimed to investigate the existence of potential differences in brain white matter microstructure and network connectivity between VP and FT infants at term-equivalent age (TEA) and examine the potential association of these differences with perinatal factors.
A total of 83 infants were prospectively selected for this study: 43 VP infants (gestational age, or GA: 27-32 weeks) and 40 FT infants (GA: 37-44 weeks). All infants at TEA underwent both conventional magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Significant differences in white matter fractional anisotropy (FA) and mean diffusivity (MD) images between the VP and FT groups were observed using tract-based spatial statistics (TBSS). The fibers were tracked between each pair of regions in the individual space, using the automated anatomical labeling (AAL) atlas. Then, a structural brain network was constructed, where the connection between each pair of nodes was defined by the number of fibers. Network-based statistics (NBS) were used to examine differences in brain network connectivity between the VP and FT groups. Additionally, multivariate linear regression was conducted to investigate potential correlations between fiber bundle numbers and network metrics (global efficiency, local efficiency, and small-worldness) and perinatal factors.
Significant differences in FA were observed between the VP and FT groups in several regions. These differences were found to be significantly associated with perinatal factors such as bronchopulmonary dysplasia (BPD), activity, pulse, grimace, appearance, respiratory (APGAR) score, gestational hypertension, and infection. Significant differences in network connectivity were observed between the VP and FT groups. Linear regression results showed significant correlations between maternal years of education, weight, the APGAR score, GA at birth, and network metrics in the VP group.
The findings of this study shed light on the influence of perinatal factors on brain development in VP infants. These results may serve as a basis for clinical intervention and treatment to improve the outcome of preterm infants.
Very few studies have been made to investigate functional activity changes in occult spastic diplegic cerebral palsy (SDCP). The purpose of this study was to analyze whole-brain resting state ...regional brain activity and functional connectivity (FC) changes in patients with SDCP.
We examined 12 occult SDCP and 14 healthy control subjects using resting-state functional magnetic resonance imaging. The data were analyzed using Resting-State fMRI Data Analysis Toolkit (REST) software. The regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), and whole brain FC of the motor cortex and thalamus were analyzed and compared between the occult SDCP and control groups.
Compared with the control group, the occult SDCP group showed decreased ReHo regions, including the bilateral frontal, parietal, and temporal lobes, the cerebellum, right cingulate gyrus, and right lenticular nucleus, whereas an increased ReHo value was observed in the left precuneus, calcarine, fusiform gyrus, and right precuneus. Compared with the control group, no significant differences in ALFF were noted in the occult SDCP group. With the motor cortex as the region of interest, the occult SDCP group showed decreased connectivity regions in the bilateral fusiform and lingual gyrus, but increased connectivity regions in the contralateral precentral and postcentral gyrus, supplementary motor area, and the ipsilateral postcentral gyrus. With the thalamus being regarded as the region of interest, the occult SDCP group showed decreased connectivity regions in the bilateral basal ganglia, cingulate, and prefrontal cortex, but increased connectivity regions in the bilateral precentral gyrus, the contralateral cerebellum, and inferior temporal gyrus.
Resting-state regional brain activities and FC changes in the patients with occult SDCP exhibited a special distribution pattern, which is consistent with the pathology of the disease.
Spastic diplegic cerebral palsy (SDCP) is a common type of cerebral palsy (CP), which presents as a group of motor-impairment syndromes. Previous conventional MRI studies have reported abnormal ...structural changes in SDCP, such as periventricular leucomalacia. However, there are roughly 27.8% SDCP patients presenting normal appearance in conventional MRI, which were considered as occult SDCP. In this study, sixteen patients with occult SDCP and 16 age- and sex-matched healthy control subjects were collected and the data were acquired on a 3T MR system. We applied voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analysis to investigate whole brain grey and white matter injury in occult SDCP. By using VBM method, the grey matter volume reduction was revealed in the bilateral basal ganglia regions, thalamus, insula, and left cerebral peduncle, whereas the white matter atrophy was found to be located in the posterior part of corpus callosum and right posterior corona radiata in the occult SDCP patients. By using TBSS, reduced fractional anisotropy (FA) values were detected in multiple white matter regions, including bilateral white matter tracts in prefrontal lobe, temporal lobe, internal and external capsule, corpus callosum, cingulum, thalamus, brainstem and cerebellum. Additionally, several regions of white matter tracts injury were found to be significantly correlated with motor dysfunction. These results collectively revealed the spatial patterns of whole brain grey and white matter injury in occult SDCP.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To investigate the application of multiparametric magnetic resonance imaging (mp-MRI) for comprehensive evaluation of the correlation between the characteristics of the transitional zone and the ...International Prostate Symptom Score (IPSS) in patients with benign prostatic hyperplasia (BPH).
We retrospectively recruited 210 patients with biopsy-proven BPH who underwent preoperative mp-MRI and were assigned an IPSS. The evaluation indicators included prostate volumetric parameters (total prostate volume TPV, transition zone volume TZV, and transition zone index TZI, TZI=TZV/TPV), prostate morphological parameters (intravesical prostatic protrusion, and presumed circle area ratio) and prostate compositional parameters (apparent diffusion coefficient ADC, and mean signal intensity of T2WI mean-SI-T2WI). The Pearson (r) correlation coefficient, one-way analysis of variance, and multiple linear regression analysis were used to build a regression model for evaluating the correlation between MRI-derived parameters and IPSS, IPSS-storage symptom, IPSS-voiding symptom.
Significant correlations were found between IPSS, IPSS-storage symptom, IPSS-voiding symptom, and prostate MRI-derived parameters, including TPV (r = 0.350; r = 0.466; r = 0.225, P < .001), TZV (r = 0.374; r = 0.492; r = 0.243, P < .001), TZI (r = 0.383; r = 0.313; r = 0.354, P < .001), presumed circle area ratio (r = 0.481; r = 0.356; r = 0.469, P < .001), ADC(r = -0.198; r = -0.053; r = -0.239, P < .05) and mean-SI-T2WI (r = -0.626; r = -0.310; r = -0.687, P < .001), respectively. Based on multiple linear regression analysis, the impact of mean-SI-T2WI and TZI on total IPSS were statistically significant (P < .05), and the regression equation established with the analysis (IPSS= 39.224 + 8.469 ×TZI+ (-0.09)× (mean-SI-T2WI)) was statistically significant (F=104.995, P < .001).
Mp-MRI could be used to evaluate the volume and morphology of BPH. In particular, mean-SI-T2WI and ADC could be used to describe the internal composition of the prostate. The imaging parameters were effective for evaluating BPH.
Bronchopulmonary dysplasia (BPD) affects the microstructure of white matter in preterm infants, but its influence on the changes of the brain structural network has not been elaborated. This study ...aims to investigate the connectivity characteristics of the brain structural network of BPD by using diffusion tensor imaging.
Thirty-three infants with BPD and 26 infants without BPD were enrolled in this study. Brain structural networks were constructed utilizing automated anatomic labeling mapping by tracing the fibers between each pair of regions in individual space. We calculated network metrics such as global efficiency, local efficiency, clustering coefficients, characteristic path length, and small-worldness. Then we compared the network metrics of these infants with those of 57 healthy term infants of comparable postmenstrual age at magnetic resonance imaging scan. Finally, network-based statistics was used to analyze the differences in brain network connectivity between the groups with and without BPD.
Preterm infants with BPD had higher local efficiency and clustering coefficient, lower global efficiency, and longer characteristic path length. Also, preterm infants with BPD had decreased strength of limbic connections mainly in four brain regions: the left lingual gyrus, the left calcarine fissure and surrounding cortex, the right parahippocampal gyrus, and the left precuneus.
Our findings suggest that preterm infants with BPD have lower network integration and higher segregation at term-equivalent age, which may reflect a compensatory mechanism. In addition, BPD affects brain regions involved in visual as well as cognitive functions; these findings provide a new approach to diagnose potential brain damage in preterm infants with BPD.
To clarify the clinical, diagnostic, and treatment characteristics of orbital liposarcoma.
Retrospective observational case series.
A review was performed of electronic medical records, ...histopathology, radiological images, and follow-up information for 21 patients with orbital liposarcoma.
The predominant clinical manifestation of this disease was painless exophthalmos. The most frequently encountered pathological types were well-differentiated and myxoid liposarcoma. Preoperative radiological images from 15 patients showed that orbital liposarcoma initially developed in extraocular muscle in 9 patients. Furthermore, all well-differentiated liposarcomas exhibited the radiographic characteristics of irregular and ill-defined adipose tissue, whereas only 12.5% of myxoid liposarcomas had the imaging characteristics. For the patients who exclusively underwent surgery, all of those with subtotal excisions experienced recurrence, 63.6% of marginal excisions recurred, and 50% of wide excisions resulted in recurrence. However, none of the patients who underwent marginal excisions or wide excisions combined with adjuvant radiotherapy exhibited recurrence. The analysis of magnetic resonance imaging findings in 3 patients who underwent neoadjuvant radiotherapy revealed that the tumor size remained stable in a patient with well-differentiated liposarcoma, whereas another patient with the same type of tumor exhibited a gradual increase in size. Conversely, a patient with myxoid liposarcoma experienced a significant reduction in tumor size following neoadjuvant radiotherapy.
Orbital liposarcoma demonstrated a propensity for developing in the extraocular muscle. The radiological images of orbital well-differentiated liposarcomas were characterized by irregular and ill-defined adipose tissue. Surgery combined with radiotherapy demonstrated potential in reducing recurrence rates. Notably, orbital myxoid liposarcoma exhibited greater sensitivity to radiotherapy compared to well-differentiated liposarcoma.
Objective
Glioma is a devastating disease lacking effective treatment. Tumor electric field therapy is emerging as a novel non‐invasive therapy. The current study evaluates the efficacy and safety of ...a self‐designed tumor electric field therapy system (TEFTS ASCLU‐300) in a rat orthotopic transplantation model of glioma.
Methods
A model of intracranial orthotopic transplantation was established in rats using glioma C6 cells. For electric field therapy, glioma‐bearing rats were exposed to alternating electric fields generated by a self‐developed TEFTS starting on either 1st (Group 2) or 3rd (Group 3) day after transplantation, while other conditions were maintained the same as non‐treated rats (Group 1). Glioma size, body weight, and overall survival (OS) were compared between groups. Immunohistochemical staining was applied to access tumor cell death and microvessel density within the tumor. In addition, the systemic effects of TEFTS on blood cells, vital organs, and hepatorenal functions were evaluated.
Results
TEFTS treatment significantly elongated the OS of tumor‐bearing rats compared with non‐treated rats (non‐treated vs treated: 24.77 ± 7.08 days vs 40.31 ± 19.11 days, P = .0031). Continuous TEFTS treatment starting on 1st or 3rd day significantly reduced glioma size at 2 and 3 weeks after tumor cell inoculation (Week 2: Group 1:289.95 ± 101.69 mm3; Group 2:70.45 ± 17.79 mm3; Group 3:73.88 ± 33.21 mm3, P < .0001. Week 3: Group 1:544.096 ± 78.53 mm3; Group 2:187.58 ± 78.44 mm3; Group 3:167.14 ± 109.96 mm3, P = .0005). Continuous treatment for more than 4 weeks inhibited tumor growth. The TEFTS treatment promoted tumor cell death, as demonstrated by increased number of Caspase 3+ cells within the tumor (non‐treated vs treated: 38.06 ± 10.04 vs 68.57 ± 8.09 cells/field, P = .0007), but had minimal effect on microvessel density, as shown by CD31 expression (non‐treated vs treated: 1.63 ± 0.09 vs 1.57 ± 0.13% of positively stained areas, P > .05). No remarkable differences were observed in hepatorenal function, blood cell counts, or other vital organs between non‐treated and treated groups.
Conclusion
The TEFTS developed by our research team was proved to be effective and safe to inhibit tumor growth and improve general outcomes in a rat model of brain glioma.
The self‐designed TEFTS was proved to be effective and safe to inhibit tumor growth and improve general outcomes of Glioma.The instrument with random sequential electric field direction and adjustable intensity and frequency can apply electric field to the rapidly proliferating tumor cells from all directions in order to achieve the best curative effects.
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