Gray and white matter abnormalities in children with type 2 and 3 SMA: A morphological assessment.

This study investigated the changes in brain gray and white matter structure in SMA patients and their correlation with the severity of the disease. A total of 43 SMA patients (including 22 type II and 21 type III SMA patients) and 37 healthy controls were evaluated by MRI. The gray matter volume, gray matter thickness, gray matter surface area, and white matter volume of designated brain regions automatically segmented by FreeSurfer, were compared. We evaluate clinical characteristics of SMA and study the correlation between clinical characteristics and structural changes. SMA showed significant bilateral cortical superficial area loss in the frontal, parietal, and temporal lobes and global white matter volume decreases. Moreover, these patients were also found with an increased mean thickness of entire brain and right gray matter. An increased right postcentral gyrus superficial area, right central sulcus volume, and white matter volume of the right postcentral were associated with higher HFMSE scores. CONCLUSION: Type 2 and 3 children SMA had extensive, multifocal, symmetrical gray and white matter alterations. Postcentral gyrus degeneration of SMA was associated with the severity of muscular atrophy. The lack of SMN protein possibly interacted with cerebellar structural changes in somatosensory areas. WHAT IS KNOWN: • MRI has found brain changes in SMA patients, however, there is no unified conclusion and lack of correlation with clinical degree in children SMA with type 2-3. WHAT IS NEW: • Type II and II children SMA had extensive, multifocal, symmetrical gray and white matter alterations. Postcentral gyrus degeneration of SMA was associated with the severity of muscular atrophy. Cerebellar structural changes in somatosensory areas may attribute to the lack of SMN protein.

Assessment of the glymphatic function in children with attention-deficit/hyperactivity disorder.

OBJECTIVES: Whether the alternation of the glymphatic system exists in neurodevelopmental disease still remains unclear. In this study, we investigated structural and functional changes in the glymphatic system in the treatment-naïve attention-deficit/hyperactivity disorder (ADHD) children by quantitatively measuring the Virchow-Robin spaces (VRS) volume and diffusion tensor image-analysis along the perivascular space (DTI-ALPS). METHODS: Forty-seven pediatric ADHD patients and 52 age- and gender-matched typically developing (TD) children were recruited in this prospective study. The VRS volume was calculated using a semi-automated approach in axial T2-weighted images. Diffusivities along the x-, y-, and z-axes in the projection, association, and subcortical neural fiber areas were measured. The ALPS index, a ratio that accentuated water diffusion along the perivascular space, was calculated. The Mann-Whitney U test was used to compare the quantitative parameters; Pearson's correlation was used to analyze the correlation with clinical symptoms. RESULTS: The cerebral VRS volume (mean, 15.514 mL vs. 11.702 mL) and the VRS volume ratio in the ADHD group were larger than those in the TD group (all p < 0.001). The diffusivity along the x-axis in association fiber area and ALPS index were significantly smaller in the ADHD group vs. TD group (mean, 1.40 vs.1.59, p < 0.05 after false discovery rate adjustment). Besides, the ALPS index was related to inattention symptoms of ADHD (r = - 0.323, p < 0.05). CONCLUSIONS: Our study suggests that the glymphatic system alternation may participate in the pathogenesis of ADHD, which may be a new research direction for exploring the mechanisms of psycho-behavioral developmental disorders. Moreover, the VRS volume and ALPS index could be used as the metrics for diagnosing ADHD. CLINICAL RELEVANCE STATEMENT: Considering the potential relevance of the glymphatic system for exploring the mechanisms of attention deficit/hyperactivity, the Virchow-Robin spaces volume and the analysis along the perivascular space index could be used as additional metrics for diagnosing the disorder. KEY POINTS: • Increased Virchow-Robin space volume and decreased analysis along the perivascular space index were found in the treatment-naïve attention-deficit/hyperactivity disorder children. • The results of this study indicate that the glymphatic system alternation may have a valuable role in the pathogenesis of attention-deficit/hyperactivity disorder. • The analysis along the perivascular space index is correlated with inattention symptoms of attention-deficit/hyperactivity disorder children.

Quantification of myelination in children with attention-deficit/hyperactivity disorder: a comparative assessment with synthetic MRI and DTI.

Evaluation of myelin content is crucial for attention-deficit/hyperactivity disorder (ADHD). To estimate myelin content in ADHD based on synthetic MRI-based method and compare it with established diffusion tensor imaging (DTI) method. Fifth-nine ADHD and fifty typically developing (TD) children were recruited. Global and regional myelin content (myelin volume fraction [MVF] and myelin volume [MYV]) were assessed using SyMRI and compared with DTI metrics (fractional anisotropy and mean/radial/axial diffusivity). The relationship between significant MRI parameters and clinical variables were assessed in ADHD. No between-group differences of whole-brain myelin content were found. Compared to TDs, ADHD showed higher mean MVF in bilateral internal capsule, external capsule, corona radiata, and corpus callosum, as well as in left tapetum, left superior fronto-occipital fascicular, and right cingulum (all PFDR-corrected < 0.05). Increased MYV were found in similar regions. Abnormalities of DTI metrics were mainly in bilateral corticospinal tract. Besides, MVF in right retro lenticular part of internal capsule was negatively correlated with cancellation test scores (r = - 0.41, P = 0.002), and MYV in right posterior limb of internal capsule (r = 0.377, P = 0.040) and left superior corona radiata (r = 0.375, P = 0.041) were positively correlated with cancellation test scores in ADHD. Increased myelin content underscored the important pathway of frontostriatal tract, posterior thalamic radiation, and corpus callosum underlying ADHD, which reinforced the insights into myelin quantification and its potential role in pathophysiological mechanism and disease diagnosis. Prospectively registered trials number: ChiCTR2100048109; date: 2021-07.

Disrupted small-world networks in children with drug-naïve atten-tion-deficit/hyperactivity disorder: a DTI-based network analysis.

OBJECTIVES: To explore the alterations in the white matter (WM) structural connectome in children with drug-naïve attention-deficit/hyperactivity disorder (ADHD). METHODS: Forty-nine pediatric ADHD and 51 age- and gender-matched typically developing (TD) children aged 6-14 years old were enrolled. This cross-sectional study applied graph theoretical analysis to assess the white matter organization based on deterministic diffusion tensor imaging (DTI). WM structural connectivity was constructed in 90 cortical and subcor-tical regions, and topological parameters of the resulting graphs were calculated. Networks were compared between two groups. The digit cancellation test (DCT) was taken to evaluate clinical symptom severity in pediatric ADHD, using the concentration index and the total cancellation test scores. Then, a partial correlation analysis was performed to explore the re-lationship between significant topologic metrics and clinical symptom severity. RESULTS: Compared to TDs, ADHD showed an increase in the characteristic path length (Lp), normalized clustering coefficient (γ), small-worldness (σ), and a decrease in the global effi-ciency (Eglob) (all P <0.05). Furthermore, ADHD showed reduced nodal centralities mainly in the regions of default mode (DMN), central executive network (CEN), basal ganglia, and bilateral thalamus (all P <0.05). After performing Benjamini-Hochberg's procedure, only left orbital part of superior frontal gyrus (ORBsup.L) and left caudate (CAU) were statistically significant (P < 0.05, FDR-corrected). In addition, the concentration index of ADHD was negatively correlated with the nodal betweenness of the left orbital part of the middle frontal gyrus (ORBmid.L) (r = -0.302, P = 0.042). CONCLUSIONS: Our findings revealed an ADHD-related shift of WM network topology toward "regularization" pattern, characterized by decreased global network integration, which is also reflected by changed nodal centralities involving DMN, CEN, basal ganglia, and bilateral thalamus. ADHD could be understood by examining the dysfunction of large-scale spatially distributed neural networks.

Quantitative assessment of extraocular muscles in Graves' ophthalmopathy using T1 mapping.

OBJECTIVE: To evaluate the performance of T1 mapping in the characterization of extraocular muscles (EOMs) of Graves' ophthalmopathy (GO) patients and investigate its feasibility in assessing the response to glucocorticoid therapy in active GO patients. METHODS: A total of 133 participants (78 active GO, 23 inactive GO, 18 Graves' disease (GD) patients, and 14 healthy volunteers) were consecutively enrolled from July 2018 to December 2020. Native T1 (nT1) and postcontrast T1 (cT1) values of EOMs were measured and compared. The variations in T1 mapping metrics of EOMs were compared pre/post glucocorticoid treatment in 23 follow-up active GO patients. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed. RESULTS: The nT1 of EOMs in GO patients was higher than that in GD patients and healthy volunteers. The nT1 of superior rectus (SR) in active GO was higher than that in inactive GO patients, and it could be used as a potential marker of GO activity (OR: 1.003; 95% CI: 1.001, 1.004), with a diagnostic sensitivity of 86.3% and specificity of 43.7%. Meanwhile, the cT1 of SR, inferior rectus (IR), and medial rectus (MR) in inactive GO patients were higher than those in active GO patients. The nT1 of EOMs achieved sufficient diagnostic performance in evaluating the response to glucocorticoid therapy for follow-up active GO patients (AUC, 0.797; sensitivity, 71.9%; specificity, 85.7%). CONCLUSIONS: T1 mapping could quantitatively assess the activity of GO and the response to glucocorticoid therapy in active GO patients and may even potentially reflect the fibrosis of EOMs. CLINICAL RELEVANCE STATEMENT: T1 values can reflect the pathological status of the extraocular muscle. T1 mapping could help to quantitatively assess the clinical activity of GO and the response to glucocorticoid therapy in active GO patients. KEY POINTS: • Graves' ophthalmopathy patients had greater nT1 of extraocular muscles than Graves' disease patients and healthy volunteers, and nT1 of the superior rectus could be a potential marker of Graves' ophthalmopathy activity. • The cT1 of extraocular muscles in inactive Graves' ophthalmopathy patients was higher than that in active Graves' ophthalmopathy patients, and it might be associated with muscle fibrosis. • nT1 of extraocular muscles could offer sufficient diagnostic performance in evaluating the response to glucocorticoid therapy for follow-up active Graves' ophthalmopathy patients.

Glymphatic system dysfunction in pediatric acute lymphoblastic leukemia without clinically diagnosed central nervous system infiltration: a novel DTI-ALPS method.

BACKGROUND AND OBJECTIVE: Central nervous system (CNS) infiltration commonly occurs in children with acute lymphoblastic leukemia (ALL). Nevertheless, CNS infiltration is rarely detected at the initial diagnosis. The glymphatic system, which regulates cerebrospinal fluid (CSF) and interstitial fluid transport, is considered one of the possible routes of CNS infiltration by leukemia cells. In this study, we used diffusion tensor image analysis along the perivascular space (DTI-ALPS) method to investigate glymphatic system function and obtained CSF volume using synthetic magnetic resonance imaging (SyMRI) in pediatric ALL without clinically diagnosed CNS infiltration. MATERIALS AND METHODS: Twenty-nine ALL and 29 typically developing (TD) children were prospectively recruited (age 4-16 years) in the present study. Group differences in brain volumetric parameters, brain water diffusivities, and the ALPS index were evaluated after controlling for age, gender, and handedness. Furthermore, significant group-different parameters were correlated with clinical information using partial correlations analysis. RESULTS: Lower Dxassoc and ALPS index, and increased CSF volume were found in pediatric ALL (all pFDR-corrected < 0.05). Moreover, the ALPS index was negatively associated with the risk classification (r = - 0.59, pFDR-corrected = 0.04) in pediatric ALL. CONCLUSIONS: Dysfunction of the glymphatic system and accumulation of CSF were presented in pediatric ALL without clinically diagnosed CNS infiltration. These novel findings suggested that the glymphatic system might be essential in the early-stage process of ALL CNS infiltration, which provides a new direction for exploring underlying mechanisms and early detection of pediatric ALL CNS infiltration. KEY POINTS: • Lower Dxassoc and ALPS index, and increased CSF volume were found in pediatric ALL (all pFDR-corrected < 0.05). • The ALPS index was negatively associated with the risk classification (r = -0.59, pFDR-corrected = 0.04) in pediatric ALL. • Dysfunction of the glymphatic system and accumulation of CSF were presented in pediatric ALL without clinically diagnosed CNS infiltration, which suggested that the ALPS index and CSF volume might be promising imaging markers for early detection of pediatric ALL CNS infiltration.

Image quality using synthetic brain MRI: an age-stratified study.

BACKGROUND: Synthetic magnetic resonance imaging (MRI) might replace the conventional MR sequences in brain evaluation to shorten scan time and obtain multiple quantitative parameters. PURPOSE: To evaluate the image quality of multiple-delay-multiple-echo (MDME) sequence-derived synthetic brain MR images compared to conventional images by considering a multi-age sample. MATERIAL AND METHODS: Image sets of conventional and synthetic MRI of 200 participants were included. On the basis of the presence of intracranial lesions, the participants were divided into a normal group and a pathological group. Two neuroradiologists compared the anonymous and unordered images. Image quality, artifacts, and diagnostic performance were analyzed. RESULTS: In the quantitative analysis, comparing with conventional images, MDME sequence-derived synthetic MRI demonstrated an equal/greater signal-to-noise ratio and contrast-to-noise ratio (CNR) in all age groups. Specifically, for participants aged ≤2 years, synthetic T2-fluid-attenuated inversion recovery imaging showed a significantly higher cerebellum gray/white matter CNR (P < 0.05). In the qualitative and artifact analyses, except for the superior sagittal sinus and cranial nerves, synthetic MRI showed good imaging quality (≥3 points) in all brain structures. On synthetic T1-weighted imaging, high signal intensity within the superior sagittal sinus was found in most of our participants (107/118, 90.7%). No difference was observed between synthetic and conventional MRI in diagnosing the lesions. CONCLUSION: MDME sequence-derived synthetic MRI showed similar image quality and diagnostic performance with a shorter acquisition time than conventional MRI. However, the high signal intensity within the superior sagittal sinus on synthetic T1-weighted images requires consideration.

Dysregulation of miR-411 in cancer: Causative factor for pathogenesis, diagnosis and prognosis.

MiRNA accounts for 1-3% of genes but regulates more than 30% of gene expression in humans. This article analyzes the current deficiencies and challenges of miR-411 research and looks forward to the prospects of miR-411 in cancer. MiR-411 is a non-coding RNA located on chromosome 14. MiR-411 is abnormally expressed in a variety of cancers. The dysregulation of miR-411 can affect cancer cell proliferation, invasion, migration, apoptosis, colony formation, etc. miR-411 can be regulated by different lncRNAs and circRNAs. By targeting multiple genes, miR-411 participates in the activation of the MAPK signaling pathway, PI3K/AKT/mTOR signaling pathway, p53 signaling pathway, Ras signaling pathway, NF-κB signaling pathway, and Wnt/ß-catenin signaling pathway. The expression of miR-411 is related to the diagnosis, prognosis, and sensitivity of drugs in cancer patients. In conclusion, this work outlines the molecular mechanisms and cellular functions of aberrant expression of miR-411 and its target genes in cancer to reveal its potential value in diagnosis, prognosis, and drug sensitivity.

Quantitative susceptibility mapping reveals brain iron deficiency in children with attention-deficit/hyperactivity disorder: a whole-brain analysis.

OBJECTIVES: To quantitatively measure and compare the whole-brain iron deposition between attention-deficit/hyperactivity disorder (ADHD) patients and typically developing (TD) children using the quantitative susceptibility mapping (QSM) technique. METHODS: This study was approved by the institutional review board of our institution (No. [2019]328). Fifty-one patients between 6 and 14 years with clinical diagnosis of ADHD and 51 age- and gender-paired TD children were enrolled. For each participant, the 3D T1 and multi-echo GRE sequence were performed to acquire the whole-brain data with 3.0-T MRI. The QSM maps were calculated using STISuite toolbox. After normalizing the QSM images to MNI space, the voxel-based analysis was used to compare the iron content between the two groups. Pearson's correlation test was used to assess the associations between the iron content and the score of the tablet-PC-based cancellation test, which was done to evaluate the attention concentration level. RESULTS: Iron deficiency was observed in several brain regions in children with ADHD, including bilateral striatums, anterior cingulum, olfactory gyrus, and right lingual gyri. In further correlation analysis, the left anterior cingulum was found to show positive correlation with the symptom severity (r = 0.326, p < 0.05). CONCLUSIONS: Our study demonstrated that the iron deficiency in several brain regions might be related with ADHD, which might be valuable for further studies. And QSM might have the potential efficacy in the auxiliary diagnosis of ADHD. KEY POINTS: • Iron deficiency was observed in several brain regions in children with ADHD, which include bilateral striatums, the critical regions in the dopaminergic transmitter system. • The iron content in the left ACG may have association with the symptom severity of ADHD. • QSM might have the potential efficacy in the auxiliary diagnosis of ADHD.

Multiparametric quantitative MRI for the evaluation of dysthyroid optic neuropathy.

OBJECTIVE: To evaluate the ability of quantitative MRI parameters for predicting dysthyroid optic neuropathy (DON). METHODS: We retrospectively collected and analyzed the clinical features and 3.0 T MRI data of 59 patients with Graves orbitopathy (GO), with (n = 26) and without DON (n = 33). We compared MRI quantitative parameters, including the modified muscle index (mMI), proptosis, volume of intra-orbital fat, mean apparent diffusion coefficient value, and T2 value of the optic nerve among patients with and without DON. A logistic regression analysis was performed to identify the risk factors associated with DON. Moreover, we performed a receiver operating characteristic curve analysis and decision curve analysis to evaluate the diagnostic performance of the identified parameters for DON. RESULTS: We studied 118 orbits (43 and 75 with and without DON, respectively). The mMI and mean T2 value of the optic nerve were significantly greater in orbits with DON (p < 0.001). A greater mMI at 21 mm (odds ratio (OR), 1.039; 95% confidence interval (CI): 1.019, 1.058) and higher mean T2 value of the optic nerve (OR, 1.035; 95% CI: 1.017, 1.054) were associated with a higher risk of DON. A model combining the mMI at 21 mm and mean T2 values for the optic nerve effectively predicted DON in patients with GO, with a sensitivity and specificity of 95.3% and 76%, respectively. CONCLUSION: A quantitative MRI parameter combining the mMI at 21 mm and mean T2 value of the optic nerve can be an effective imaging marker for identifying DON. KEY POINTS: • Patients with GO and DON had greater mMI than those without DON. • Optic nerves in patients with DON demonstrated an increased T2 value. • The quantitative MRI parameter combining the mMI at 21 mm and mean T2 value of the optic nerve is the most effective method for diagnosing DON.

Quantitative synthetic MRI reveals grey matter abnormalities in children with drug-naïve attention-deficit/hyperactivity disorder.

To investigate the quantitative profiles of brain grey matter (GM) in pediatric drug-naïve ADHD patients using synthetic magnetic resonance imaging (SyMRI). A total of 37 drug-naïve pediatric ADHD and 27 age- and gender-matched healthy controls (HC) were enrolled in this study. Each subject underwent both SyMRI and conventional 3D T1-FSPGR scans. Quantitative parameters, T1 and T2 maps, were extracted from the SyMRI data. Between-group quantitative maps were compared using a general linear model analysis. Pearson correlation analysis was conducted to assess the association between significantly altered MR indices and clinical measurements in ADHD. Compared with the HC group, altered T1 and T2 relaxometry times in the ADHD group were mainly distributed in GM regions of the cerebellum, attention and execution control network, default mode network, and limbic areas. Moreover, the T1 value of the right cerebellum 8 was negatively correlated with the attention concentration level in ADHD (R = 0.140, P = 0.0225). With regards to T2 map, the associations were observed between the attention level of ADHD patients and left fusiform gyrus (R = 0.251, P = 0.0016), and right cerebellum crus2 (R = 0.142, P = 0.0214). Altered T1, T2 values found in specific regions of GM, including cerebellum, attention and execution control network, default mode network, and limbic areas, may reveal widespread micromorphology changes, i.e., brain iron deficiency, low myelin content, and enlarged vascular interstitial space in ADHD patients. Thus, T1, T2 values might be promising imaging markers for future ADHD studies.

Dysfunction of miR-802 in tumors.

Recent studies have shown that miR-802 is abnormally expressed in many tumors. miR-802 is expressed at low levels in tissues and cells of gastric cancer, colorectal cancer, breast cancer, cervical cancer, epithelial ovarian cancer, tongue squamous cell carcinoma, oral squamous cell carcinoma, esophageal squamous cell carcinoma, laryngeal squamous cell carcinoma, and melanoma. In contrast, miR-802 is overexpressed in hepatocellular carcinoma, bladder urothelial cancer, osteosarcoma, and cholesteatoma tissue cells. It should be noted that the results of studies on the expression of miR-802 in pancreatic cancer, prostate cancer, and lung cancer are inconsistent. Current studies have found that miR-802 can target and regulate genes in different tumors, and affect the regulation of the Wnt signaling pathway, EMT signaling pathway, PI3K/AKT signaling pathway, ERK signaling pathway, and Hedgehog signaling pathway. At the same time, miR-802 is regulated by the endogenous competition of four ceRNAs, including circDONSON, IGFL2-AS1, MIR155HG, and MIR4435-2HG. This article reviews the abnormal expression of miR-802 in a variety of tumors, expounds the mechanism by which miR-802 affects tumor progression by regulating different target genes, and elaborates the network of miR-802-related ceRNAs. We also summarized the limitations of miR-802 research and looked forward to the potential application of miR-802 in the diagnosis and prognosis of tumors.

Utility of multi-parametric quantitative magnetic resonance imaging of the lacrimal gland for diagnosing and staging Graves' ophthalmopathy.

PURPOSE: To explore radiological changes of the lacrimal gland (LG) in Graves' ophthalmopathy (GO) based on multi-parametric quantitative MRI and its clinical utility in LG diagnosis and activity in GO. METHODS: We enrolled 99 consecutive patients with GO (198 eyes) and 12 Graves' Disease (GD) patients (24 eyes) from July 2018 to June 2020. Clinical, laboratory, and MRI data were collected at the first visit. Based on clinical activity scores, eyes with GO were subdivided into active and inactive groups. T2-relaxation time (T2) and the absolute reduction in T1-relaxation time (ΔT1) were determined. After MRI and processing, we performed descriptive data analysis and group comparisons. Novel logistic regression predictive models were developed for diagnosing and staging GO. Diagnostic performance of MRI parameters and models was assessed by receiver operating characteristic curve analysis. RESULTS: LG in GO group had significantly higher T2 and ΔT1 values than the GD group [106.25(95.30,120.21) vs. 83.35(78.15,91.45), P<0.001, and 662.62(539.33,810.95) vs. 547.35(458.62,585.57), P = 0.002, respectively]. The GO group had higher T2 of LG indicating higher disease activity [110.93(102.54,127.67) vs. 93.29(87.06,101.96), P < 0.001]. Combining T2 and ΔT1 values of LG, Model I had higher diagnostic value for distinguishing GO from GD (AUC=0.94, 95 %CI: 0.89,0.99, P<0.001). Meanwhile, T2 of LG had higher diagnostic value for grading GO activity (AUC = 0.84, 95 %CI: 0.76,0.92, P<0.001). CONCLUSIONS: Multi-parametric quantitative MRI parameters of the LG in GO were significantly altered. Novel models combining LG T2 and ΔT1 values showed excellent predictive performances in diagnosing GO. Furthermore, T2 of LG showed practical utility for staging GO.

Molecular Mechanisms of miR-1271 Dysregulation in Human Cancer.

MicroRNA is a small noncoding RNA that plays a role in regulating gene expression. miR-1271 is a tumor suppressor microRNA, which is related to the biological changes of many cancers. miR-1271 is considered a biomarker with a potential prognosis and high therapeutic value in tumors. Besides, the expression of miR-1271 is also regulated by many factors. In this study, we summarize the role of miR-1271 in tumors, focusing on the molecular mechanisms of the target genes of miR-1271. Our review will provide a comprehensive understanding of miR-1271 in tumors, as well as ideas for subsequent tumor research related to miR-1271.

The biological role of arachidonic acid 12-lipoxygenase (ALOX12) in various human diseases.

ALOX12 encodes arachidonic acid 12-lipoxygenase that acts on different polyunsaturated fatty acid substrates to produce biologically active lipid mediators including eicosanes and lipoxins. ALOX12 protein plays an important role in inflammation and oxidation, while abnormal DNA methylation and genetic variants of ALOX12 are associated with various human diseases and pathological phenotypes, such as cardiovascular disease, diabetes, neurodegenerative diseases, respiratory system disease, cancer, infection, etc. Here, this article reviews the mechanisms by which ALOX12 participates in related diseases, which will provide systematic knowledge for future ALOX12 related studies.

Epigenetic Changes Associated With Interleukin-10.

IL-10 is a regulator of inflammation and immunosuppression. IL-10 regulates a variety of immune cells to limit and stop the inflammatory response, and thus plays an important role in autoimmune diseases, inflammatory diseases and cancer. IL-10 is closely related to epigenetic modification, in which changes in DNA methylation of IL-10 gene can affect mRNA and protein levels of IL-10. In addition, changes in histone modifications, especially histone acetylation, can also lead to abnormal expression of IL-10 mRNA. At the same time, a handful of IL-10 related microRNAs (miRNAs) are found to be aberrantly expressed in multiple diseases. Besides, long non-coding RNA (lncRNA) growth arrest specific transcript 5 (GAS5) also inhibits IL-10 expression. Here, we reviewed the epigenetic changes related to IL-10 in various diseases, as well as the regulation of IL-10 gene expression in various diseases by epigenetic modifications such as DNA methylation, histone modification, miRNA, and lncRNA.

The Processing, Gene Regulation, Biological Functions, and Clinical Relevance of N4-Acetylcytidine on RNA: A Systematic Review.

N4-acetylcytidine (ac4C) is often considered to be a conservative, chemically modified nucleoside present on tRNA and rRNA. Recent studies have shown extensive ac4C modifications in human and yeast mRNAs. ac4C helps to correctly read codons during translation and improves translation efficiency and the stability of mRNA. At present, the research of ac4C involves a variety of detection methods. The formation of ac4C is closely related to N-acetyltransferase 10 (NAT10) and its helpers, such as putative tRNA acetyltransferase (TAN1) for tRNA ac4C and small nucleolar RNA (snoRNA) for rRNA ac4C. Also, ac4C is associated with the development, progression, and prognosis of a variety of human diseases. Here, we summarize the history of ac4C research and the detection technologies of ac4C. We then summarized the role and mechanism of ac4C in gene-expression regulation and demonstrated the relevance of ac4C to a variety of human diseases, especially cancer. Finally, we list the future challenges of the ac4C research and demonstrate a research strategy for the interactions among several abundant modified nucleosides on mRNA.

Revisiting the Blood Supply of the Rectus Femoris: A Case Report and Computed Tomography Angiography Study.

BACKGROUND: Rectus femoris necrosis is a rare but severe complication after anterolateral thigh flap (ALTF) harvesting. It has been previously reported that the blood supply of the rectus femoris (RF) often arises from the same source artery as the ALTF; however, precise descriptions of the relationship remain limited. This article revisits the blood supply of the RF based on computed tomography angiography (CTA) and analyzes the possible influence of the blood supply on the RF during ALTF harvesting. METHODS: Between December 2017 and June 2018, CTA images of the bilateral lower extremities of 25 patients were studied. The RF length, number, and diameter of branches at the entry point into muscle, location, and overall branch vessel origins were recorded. RESULTS: The average ± SD RF length was 384.73 ± 19.28 mm. There were 170 branches (mean ± SD, 3.4 ± 0.96 branches per thigh), mainly arising from the lateral circumflex femoral artery. The average ± SD diameter was 1.90 ± 0.51 mm. The first branch was located at 1/5 of the proximal site of the RF, and 91% of all branches were located above the midpoint. The RF vascularity can be classified into 2 types: type 1 (36% of sides) has branches that arise from a single artery (descending lateral circumflex femoral artery or femoral artery), whereas type 2 (64% of sides) has branches at the 1/5 proximal and 4/5 distal parts, which arise from different arteries. CONCLUSIONS: Preoperative CTA can provide anatomic information about the RF's nutrient vessel(s) and helps to optimize ALTF design.

Patterns of Failure and Survival Trends Of 720 Patients with Stage I Nasopharyngeal Carcinoma Diagnosed from 1990-2012: A Large-scale Retrospective Cohort Study.

Objectives: To evaluate the patterns of failure and survival trends of patients with stage I nasopharyngeal carcinoma (NPC) treated with radiotherapy alone over the last 20 years. Materials and Methods: A retrospective cohort study was conducted on 720 patients with stage I NPC who were treated with curative two-dimensional radiotherapy (2DRT), three-dimensional conformal radiotherapy (3DRT), or intensity-modulated radiotherapy (IMRT) between January 1990 and December 2012. The patients were categorized into four calendar periods (1990-1996, 1997-2002, 2003-2007, and 2008-2012) and four age subgroups (18-39, 40-49, 50-59, and >60). We computed overall survival (OS), progression free survival (PFS), locoregional relapse free survival (LRFS) and distant metastasis free survival (DMFS) as measures of patient survival. Results: After a median follow-up period of 105 months (range 1-280 months), we observed the increasing trends in survival and disease control. The 3-, 5-, and 7-year OS rates increased from 97.0%, 86.7%, and 81.7% in the first calendar period (1990-1996) to 100%, 99.3%, and 98.0% in the last calendar period (2008-2012), respectively (P<0.001). Additionally, significant increasing trends could be seen in the PFS and LRFS during the four calendar periods. In the subgroup analysis, the OS, PFS and LRFS in patients diagnosed older than 40 years had greater improvement than the younger patients. However, the rate of distant metastasis was stable and relatively low, as the 5-year distant metastasis rate ranged from 0.2%-2.5% among the four calendar periods. Conclusion: The survival rates in patients with stage I NPC showed increasing trends from 1990 to 2012. The advances of radiotherapy provided excellent locoregional control and enhanced overall survival, and in particular, the IMRT decreased locoregional relapse.

Combination of Tumor Volume and Epstein-Barr Virus DNA Improved Prognostic Stratification of Stage II Nasopharyngeal Carcinoma in the Intensity Modulated Radiotherapy Era: A Large-Scale Cohort Study.

PURPOSE: Little is known about combination of the circulating Epstein-Barr viral (EBV) DNA and tumor volume in prognosis of stage II nasopharyngeal carcinoma (NPC) patients in the intensity modulated radiotherapy (IMRT) era. We conducted this cohort study to evaluate the prognostic values of combining these two factors. MATERIALS AND METHODS: By Kaplan-Meier, we compare the differences of survival curves between 385 patients with different EBV DNA or tumor volume levels, or with the combination of two biomarkers mentioned above. RESULTS: Gross tumor volume of cervical lymph nodes (GTVnd, p < 0.001) and total tumor volume (GTVtotal, p < 0.001) were both closely related to pretreatment EBV DNA, while gross tumor volume of nasopharynx (GTVnx, p=0.047) was weakly related to EBV DNA. EBV DNA was significantly correlated with progress-free survival (PFS, p=0.005), locoregional-free survival (LRFS, p=0.039), and distant metastasis-free survival (DMFS, p=0.017), while GTVtotal, regardless of GTVnx and GTVnd, had a significant correlation with PFS and LRFS. The p-values of GTVtotal for PFS and LRFS were 0.008 and 0.001, respectively. According to GTVtotal and pretreatment EBV DNA level, patients were divided into a low-risk group (EBV DNA 0 copy/mL, GTVtotal < 30 cm3; EBV DNA 0 copy/mL, GTVtotal ≥ 30 cm3; or EBV DNA > 0 copy/mL, GTVtotal < 30 cm3) and a high-risk group (EBV DNA > 0 copy/mL, GTVtotal ≥ 30 cm3). When patients in the low-risk group were compared with those in the high-risk group, 3-year PFS (p=0.003), LRFS (p=0.010), and DMFS (p=0.031) rates were statistically significant. CONCLUSION: Pretreatment plasma EBV DNA and tumor volume were both closely correlated with prognosis of stage II NPC patients in the IMRT era. Combination of EBV DNA and tumor volume can refine prognosis and indicate for clinical therapy.