[A Preliminary Study of Applying Geometric Deep Learning in Brain Morphometry for Diagnosis of Alzheimer's Disease].

OBJECTIVE: A predictive model of Alzheimer's disease (AD) was established based on brain surface meshes and geometric deep learning, and its performance was evaluated. METHODS: Seventy-six clinically diagnosed AD patients and 83 healthy older adults were enrolled and randomly assigned to the training set and the test set according to a 4-to-1 ratio. Brain surface mesh was constructed from 3-D T1-weighted high-resolution structural MR volumes of each participant. After applying a series of simplification to the surface meshes, the training set was fed into the geometric deep neural network for training. The performance of the prediction model was evaluated with the test set, and the evaluation metrics included accuracy, sensitivity and specificity. RESULTS: The prediction model trained on the right brain surface meshes with 6 000 faces achieved the best performance, with accuracy reaching 93.8%, sensitivity, 91.7%, and specificity, 94.1%. The evolution of the brain surface meshes during convolution and pooling revealed that AD patients had diffuse brain tissue loss compared with healthy older adults. CONCLUSION: Morphological brain analysis based on mesh data and geometric deep learning has great potential in the differential diagnosis of AD.

[Myocardial Magnetic Resonance Texture Characteristics of Healthy Volunteers].

OBJECTIVE: To determine the myocardial texture features of cardiac magnetic resonance (CMR) in healthy adult Han populations. METHODS: 59 healthy Han volunteers were recruited for this study from May 2016 to November 2017. CMR examinations were performed on the participants with a 3.0T scanner (Tim Trio, Siemens Medical Solution) to estimate the functional parameters, Native T1 value and ECV. Texture analysis (TA) was performed on the region of interest (ROI) in the left ventricle myocardium on T1 mapping images, with 40 myocardial texture features being extracted. Differences in the myocardial texture features across gender and age groups were analyzed through Student's t-tests or Wilcoxon signed-rank tests. Spearman correlations were analyzed between the myocardial texture features and age, native T1 value and extracellular volume (ECV). RESULTS: Of the 59 participants, 28 were women and 29 were in the younger age group (< 45 years old). The male participants had higher left ventricular mass index (Lvmassi) and lower native T1 than their female counterparts (P < 0.01). No gender differences in blood pressure, heart rate, left ventricular ejection fraction (LVEF) and ECV values were found. Ten of the forty myocardial texture features showed gender differences, including two first order features and eight Grey-level co-occurrence matrix (GLCM) features. Gender differences appeared in five first order features and eight GLCM features in the younger group (< 45 years old), but not in the older group (≥45 years old). Eight myocardial texture features were correlated with age, including five first order features and three GLCM features (all P < 0.01). Six first-order texture features were correlated with Native T1 values of the left ventricle middle myocardium. Three first-order texture features were correlated with ECV. CONCLUSION: Myocardial texture features in T1 mapping images vary by gender and age in healthy Han populations.

Voxel-wise meta-analyses of brain blood flow and local synchrony abnormalities in medication-free patients with major depressive disorder.

BACKGROUND: Published meta-analyses of resting-state regional cerebral blood flow (rCBF) studies of major depressive disorder (MDD) have included patients receiving antidepressants, which might affect brain activity and thus bias the results. To our knowledge, no meta-analysis has investigated regional homogeneity changes in medication-free patients with MDD. Moreover, an association between regional homogeneity and rCBF has been demonstrated in some brain regions in healthy controls. We sought to explore to what extent resting-state rCBF and regional homogeneity changes co-occur in the depressed brain without the potential confound of medication. METHODS: Using the effect-size signed differential mapping method, we conducted 2 meta-analyses of rCBF and regional homogeneity studies of medication-free patients with MDD. RESULTS: Our systematic search identified 14 rCBF studies and 9 regional homogeneity studies. We identified conjoint decreases in resting-state rCBF and regional homogeneity in the insula and superior temporal gyrus in medication-free patients with MDD compared with controls. Other changes included altered resting-state rCBF in the precuneus and in the frontal-limbic-thalamic-striatal neural circuit as well as altered regional homogeneity in the uncus and parahippocampal gyrus. Meta-regression revealed that the percentage of female patients with MDD was negatively associated with resting-state rCBF in the right anterior cingulate cortex and that the age of patients with MDD was negatively associated with rCBF in the left insula and with regional homogeneity in the left uncus. LIMITATIONS: The analysis techniques, patient characteristics and clinical variables of the included studies were heterogeneous. CONCLUSION: The conjoint alterations of rCBF and regional homogeneity in the insula and superior temporal gyrus may be core neuropathological changes in medication-free patients with MDD and serve as a specific region of interest for further studies on MDD.

[Real-time quantitative detection of E2A-PBX1 fusion gene in children with acute lymphoblastic leukemia and its clinical application in minimal residual disease monitoring].

OBJECTIVE: To establish a real-time reverse transcription-polymerase chain reaction (RT-PCR) for quantitative detection of E2A-PBX1 fusion gene mRNA in acute lymphoblastic leukemia (ALL) children and to explore its clinical significance in minimal residual disease monitoring and prognosis evaluation. METHODS: Real-time RT-PCR was used to quantitatively detect the mRNA expression of E2A-PBX1 gene in 11 newly diagnosed ALL patients at diagnosis (11 cases), complete remission (11 cases) and periods of relapse (3 cases). Ten children with normal bone marrow cell morphology and without hematopathy or tumor diseases were used as the control group. RESULTS: The median expression levels of E2A-PBX1 fusion gene in the ALL group at diagnosis and the relapse group were significantly higher than in the control and complete remission groups (P<0.01). Compared with E2A-PBX1 negative patients on day 33 during induction of remission, the recurrence rate increased and disease free survival rate at 3 year decreased significantly in E2A-PBX1 positive patients decreased (P<0.05). CONCLUSIONS: Measurement of E2A-PBX1 levels by real-time RT-PCR is useful for monitoing minimal residual disease, prediction of relapse and individual treatment. The expression level of E2A-PBX1 gene on day 33 during induction of remission can be used for prognosis evaluation.

Expression of SOCS3 throughout liver regeneration is not regulated by DNA methylation.

BACKGROUND: While suppressor of cytokine signaling 3 (SOCS3) plays a crucial role in suppressing dysplasia and tumorigenesis, it also offers a typical instance of DNA methylation in the regulation of gene transcription, since the promoter region of the SOCS3 gene is rich in CpG islands (CGIs). During liver regeneration initiated by partial hepatectomy, SOCS3 acts as a suppressor to balance the acute-phase response and terminate the regeneration. This study aimed to determine whether the variation of SOCS3 expression throughout liver regeneration is also regulated by its DNA methylation. METHODS: We established a 70% partial hepatectomy mouse model and the animals were sacrificed at indicated times to assess the SOCS3 expression. We performed bisulfite sequencing PCR and DNA sequencing to investigate the detailed cytosine methylation in the SOCS3 gene. RESULTS: Within the promoter sequence, 58 CGIs were identified and 30 were found variously methylated before or after operation; however, methylation remained at a very low level. No evidence indicated that the total methylation level or the methylation of any CpG site regularly changed throughout liver regeneration. CONCLUSION: DNA methylation or demethylation seems to be a relatively stable modification of cytosine, but not a dynamic and reversible process to regulate gene transcription in daily and acute pathophysiological events.

[Detection of WT1 gene in acute myeloid leukemia children by real-time fluorescent quantitative RT-PCR and its clinical significance].

Objective of this study was to establish a SYBR Green Ireal-time reverse transcription-polymerase chain reaction (RT-PCR) for quantitative detection of WT1 gene mRNA in children with acute myeloid leukemia (AML) and investigate its clinical significance. SYBR Green Ireal-time RT-PCR was used to quantitatively detect the mRNA expression of WT1 gene in 30 newly diagnosed AML patients, 12 cases of remission (30), 18 relapsed patients and 30 cases of normal bone marrow cell morphology, and dynamically to detect the expression of WT1 gene in 20 newly diagnosed AML children. ABL served as internal reference gene, and the 2(-ΔΔct) method was used to calculate the relative expression. The results showed that (1) the expression of WT1 gene in newly diagnosed AML children was higher than that of the normal controls and the patients with remission (p < 0.001); there were no significant difference of WT1 gene expression between AML patients with remission and normal controls (p > 0.05), which were same as in relapsed patients and newly diagnosed patients (p > 0.05); (2) WT1 gene in 20 newly diagnosed AML children highly expressed before the children were initially treated, decreased when they were complete remission, then expression increased again when their AML relapsed. The WT1 gene expression level began to rise in 5 cases before clinical relapse at 5 - 7 months; (3) the complete remission rate (CR) and 3 year overall survival (OS) did not show significant difference between the WT1-positive group and negative group when dynamically monitoring WT1 gene expression of 20 newly diagnosed children with AML. 3-year OS of WT1-positive group at the 22 - 30 days after initial treatment was significantly lower than that of the negative group (p < 0.05). It is concluded that SYBR Green Ireal-time RT-PCR is a rapid, efficient, sensitive and specific method. WT1 gene in AML childhood plays a role of cancer-promoting. The change of WT1 gene expression level contributes to evaluate the therapeutic efficacy, detect the minimal residual diseases and analyze the prognosis.

Osteogenic differentiation of mesenchymal stem cells promoted by overexpression of connective tissue growth factor.

OBJECTIVE: Large segmental bone defect repair remains a clinical and scientific challenge with increasing interest focusing on combining gene transfection with tissue engineering techniques. The aim of this study is to investigate the effect of connective tissue growth factor (CTGF) on the proliferation and osteogenic differentiation of the bone marrow mesenchymal stem cells (MSCs). METHODS: A CTGF-expressing plasmid (pCTGF) was constructed and transfected into MSCs. Then expressions of bone morphogenesis-related genes, proliferation rate, alkaline phosphatase activity, and mineralization were examined to evaluate the osteogenic potential of the CTGF gene-modified MSCs. RESULTS: Overexpression of CTGF was confirmed in pCTGF-MSCs. pCTGF transfection significantly enhanced the proliferation rates of pCTGF-MSCs (P<0.05). CTGF induced a 7.5-fold increase in cell migration over control (P<0.05). pCTGF transfection enhanced the expression of bone matrix proteins, such as bone sialoprotein, osteocalcin, and collagen type I in MSCs. The levels of alkaline phosphatase (ALP) activities of pCTGF-MSCs at the 1st and 2nd weeks were 4.0- and 3.0-fold higher than those of MSCs cultured in OS-medium, significantly higher than those of mock-MSCs and normal control MSCs (P<0.05). Overexpression of CTGF in MSCs enhanced the capability to form mineralized nodules. CONCLUSION: Overexpression of CTGF could improve the osteogenic differentiation ability of MSCs, and the CTGF gene-modified MSCs are potential as novel cell resources of bone tissue engineering.