Objective To investigate the effects of Netrin-1 on angiogenesis in vitro and in vivo. Methods We performed in vitro rat aortic ring assay and in vivo Matrigel plug assay to determine the effect of Netrin-1 on angiogenesis. Results 10 μg/L, 50 μg/L and 100 μg/L Netrin-1 stimulated microvessel sprouting from the adventitia of aortic rings and the effect reached maximum at 50 μg/L The in vivo Matrigel plug assay showed orange color change if Nestrin-1 was positive; and CD34 immunofluorescent staining showed vascular structures in the Matrigel plug with hemachrome ( 53.4 ± 7. 3 ), which was significantly higher than control ( 5. 8 ± 0. 9 )Conclusions Netrin-1 can induce angiogenesis in vitro and in vivo.

This study investigated the role of netrin-1 in placental vascular development. In vitro rat aortic ring assay and in vivo Matrigel plug assay were conducted to exmaine the effect of netrin-1 on angiogenesis. Human placental microvascular endothelial cells (HPMECs) were isolated and cultured and their viability, migration and tubular formation were studied, in order to examine the effects of netrin-1. The results showed that netrin-1 potently stimulated neovascularization in a mouse Matrigel plug in vivo and the sprouting of endothelial cells in rat aortic rings in vitro. In addition, netrin-1 enhanced the viability, migration and tube formation of HPMECs. Our study suggested that netrin-1 could significantly promote the formation of blood vessels of human placenta and may be a potential target for developing new therapeutic strategies for placental vasculature-related diseases.

Objective:To analyze the clinical characteristics of patients with eosinophilic granulo-matosis with polyangiitis (EGPA) and improve the understanding of the disease.Methods:EGPA patients who fulfilled the 1990 American College of Rheumatology (ACR) classification criteria were recruited from Sun Yat-sen Memorial Hospital Sun Yat-sen University between December 2003 and April 2020. Their demographic characteristics, clinical manifestations, laboratory and auxiliary examinations were analyzed retrospectively. Mann-whitney U test and χ2 test were used for statistical analysis. Results:Among 52 EGPA patients, 34 (65.4%) were males and the median age at disease onset was 47(38-55) years. The median time from disease onset to diagnosis was 30(4-96) months. The most common initial symptoms were respiratory (61.5%) and nose/paranasal sinus (21.2%) involvement. The most common department for the first visit was respiratory medicine (53.8%), followed by rheumatology (11.5%). 44.2% EGPA patients were diagnosed by rheumatologists. The most common clinical manifestations were asthma (88.5%), nose/paranasal sinusitis (84.6%), pulmonary (76.9%) and nervous system (61.5%) in volvement. Eight(15.4%) patients were positive for antineutrophil cytoplasmic antibodies (ANCA). Patients with positive ANCA had lower incidence of asthma, but higher incidence of general symptoms especially arthralgia and renal involvement, elevated eosinophil count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Birmingham vasculitis activity score and vasculitis damage index than patients with negative ANCA (all P<0.05). 21.2%-34.6% EGPA patients had poor prognostic factors. Conclusion:Early diagnosis of EGPA is important. EGPA patients with positive ANCA may be more severe than patients with negative ANCA. The management should be a multi-disciplinary collaboration between rheumatologists and pulmonologists.

Targeting to improve clinical thinking and practice skill of interns, modified Team-based learning (TBL) based on seeing real patient was performed for interns from eight-year clinical medicine program. Teachers prepared the corresponding case material before the teaching and made teaching aids. And interns were mobilized and guided to preview and self-study in teams. During modi-fied TBL, in-class application of seeing real patient was performed to assess the effect of self-study in teams, besides individual test and team test deriving from traditional TBL. All teams were assigned one task of seeing real patient by drawing lots, and then finished the task, answered teachers' questions. And the students' performance was given comments and comprehensive scores by the judges. After the completion of teaching, the teaching effectiveness of the modified TBL was assessed from students' performance, their scores and their teaching evaluation. Practice shows that the modified TBL can not only attract students to engage in it, but also elevate their abilities of clinical thinking and practical skill. It can also cultivate their interpersonal ability.

Objective To study influence on angiogenesis of placenta by gene silencing of netrin-1.Methods Netrin-1 gene in human umbilical vein endothelial cells(HUVEC)and placenta of pregnant rats were silenced by RNA interference.The following methods were used in this study,including the phenytetrazoliumromide(MTT)for viability,clone formation for proliferation,transwell for migration,and tube formation for angiogenesis in vitro.The change of fetal growth was recorded.Placental microvessel density in pregnant rats was measured by immunohistochemical CD34 staining in vivo.Results (1)HUVEC:viability and proliferation of HUVEC were remarkably inhibited by gene silencing of netrin-1.which number of clone formation,migration cell,tube formation were from(69±6)%,86±17,37±9 decreased to(46±5)%,46±13 and 17±5(P＜0.05)respectively.(2)Placenta of pregnant rats:after netrin-1gene silenced,fetal weight were decreased from(2.39 ±0.17)g to(2.12±0.10)g(P＜0.05).Placental microvessel density was decreased from(258±38)/mm2 to(197±32)/mm2 in vivo(P＜0.05).Conclusions Gene silencing of netrin-1 could inhibit viability,proliferation,migration,tubal formation of HUVEC and angiogcnesis of placenta.Netrin-1 plays an important role in regulating angiogenesis in placenta.

Objective To evaluate the microstructural integrity of white matter (WM) in patients with amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD) using voxel-based analysis (VBA), and investigate the relationship between WM abnormalities and gray matter(GM) atrophy.Methods Thirty-three cases with aMCI, 32 cases with mild AD and 31 normal aging volunteers as control subjects were scanned on a 3.0 T MR system using diffusion tensor imaging (DTI) and three-dimensional spoiled gradient-recalled(3DSPGR) sequences. Fractional anisotropy (FA) maps and morphological images were preprocessed by SPM5 and voxel-based comparisons between the 2 patient groups and the control group were performed by t test. Results Relative to the control group, patients with aMCI showed significantly reduced FA value in bilateral frontal, temporal and left occipital WM, left anterior part of cingulum, left inferior parietal lobule, and the W M adjacent to the triangular part of the right lateral ventricle(k≥20 voxels).In mild AD,significantly reduced FA value was found in bilateral hippocampal,inferior parietal lobular,frontal,temporal,and occipital WM,bilateral corpus callosum,anterior part of cingulums,the WM adjacent to the triaangular part of the bilateral lateral ventricles,left temporal stem,left thalamus,right precuneus(k≥20 voxels).Significantly reduced GM volume was found in left hippocampus,parahippocampal gyrus,lingual gyrus and superior temporal gyrus,bilateral insulae and middle temporal gyri in aMCl group whencompared with control group(k≥50 voxels).In mild AD,significantly reduced GM volume was found in bilateral hippoeampi,parahippocampal gyri,amygdalae,thalami,temporal,parietal,frontal,occipital cortex(k≥50 voxels).The pattern of areas with reduced FA differs;from that of the GM volumetric reduction.No areas with significantlv reduced FA was detected in aMCl compared with mild AD. There was no significant correlation between FA value of WM in patient groups and Mini-Mental State Examination(MMSE)scores.Conclusions Voxel-based MRI DTI analysis of whole brain white matter can objectively reveal widespread white matter abnormalities in early-stage AD.The difierence between WM FA reduction pattern and GM volumetric reduction pattern indicates that the pathological WM changes in earlyslage AD were caused by multiple mechanisms. FA did not vary significantly in patients pr0gressing from aMCI to mild AD and can hardly reflect the severitv of cognitive function damage in these patients.

Metal or semi-metal elements have numerous physiological and biochemical properties and have correlations with the process of occurrence and development of Zheng and Chinese herbal medicine pharmacodynamics mechanism. This article will expound the current situation of traditional Chinese medicine (TCM) research based on metal elements from the researches of Zheng, medicine theory, pharmacodynamic mechanism, prescription principles, medicine concocted theory and medicine quality control in TCM. In addition to putting forward the shortages of current researches, we also introduce metallomics, the member of Omics in systems biology to offer a new idea for modernization of TCM based on metal elements.

ObjectivesTo examine the validity of high-frequency Doppler ultrasound in identifying knees synovitis in patients with rheumatoid arthritis(RA).MethodsNinety-five consecutive patients with active RA were examined withhigh-frequency Doppler ultrasound to examine synovitis signals in knees.Synovial tissue samples of 51 patients were obtained by closed needle biopsy from knees after ultrasound examination.Serial synovial tissue sections were stained with H&E and immunohistochemical staining,and the histopathological synovitis scores were evaluated.The relationship among clinical, histopathological and ultrasound synovitis indexes was analyzed by Spearman's rank order correlation test and receiver operating characteristic curve analysis.ResultsAmong 95 RA patients,the median thickness of synovial membrane in ultrasound was 2.8 mm,the median depth of effusion was 2.7 mm; Doppler signals of synovial blood flow were detected in 82％(78/95 ) of patients and the median semiquantitive grading of synovial blood flow was 1.0.The thickness of synovial membrane and synovial blood flow at Doppler ultrasound correlated positively with histological synovitis score,hyperplasia of the lining layer,and inflammatory infiltration in sublining area (the thickness of synovial membrane:r=0.438,0.424,0.368,respectively; synovial blood flow:r=0.357,0.377,0.347,respectively; all P＜0.05).Although there was no significant difference in clinical synovitis indexes between patients with histologically low-grade and high-grade synovitis,the thickness of synovial membrane and synovial blood flow in ultrasound in patients with histologically high-grade synovitis was significantly higher than those with low-grade synovitis(P=0.001,0.036,respectively).When the thickness of synovial membrane in ultrasound was ≥ 3.9 mm,the specificity of diagnosing the high-grade synovitis was 96.7％ and the sensitivity was 61.9％.ConclusionSynovitis signals at high-frequency Doppler ultrasound correlate with histopathological synovitis,and it might be helpful in evaluating the severity of histopathological synovitis.

Objective:To reveal the abnormal topology of brain network in Alzheimer′s disease (AD), and evaluate the laterality of tau protein deposition in brains of AD patients based on 18F-APN-1607 PET brain imaging combined with graph theory. Methods:From November 2018 to January 2020, 23 clinically diagnosed AD patients (9 males, 14 females; age (61.3±10.7) years) and 13 normal controls (NC) (9 males, 4 females; age (61.6±4.5) years) who underwent 18F-APN-1607 PET imaging in Huashan Hospital, Fudan University were analyzed in this cross-sectional study. The brain network analysis method based on graph theory was used to construct the tau network of the NC group and the AD group, the network attributes (clustering coefficient, shortest path length, local efficiency, and small-worldness) were calculated, and the asymmetry index (AI) of each group to evaluate the laterality of tau protein deposition was obtained. Permutation test (1 000 times) was used to analyze the differences in brain network parameters between the NC group and the AD group. Results:The tau network of the AD group had obvious topological disorder, and the connections in the olfactory cortex and temporal lobe were weakened, while in the posterior cingulate gyrus, anterior wedge, and parietal occipital lobe, the connections were enhanced. Compared with NC group, clustering coefficient ( t values: 2.28-2.69), local efficiency ( t values: 2.34-3.06) and small-worldness ( t values: 2.26-3.32) were significantly decreased in AD group (all P<0.05) with the sparsity of 20%-50%, while the shortest path length was significantly increased ( t values: 2.13-2.85; all P<0.05). There was significant tau laterality in the posterior cingulate gyrus, superior parietal gyrus, paracentral lobule, superior temporal gyrus and middle temporal gyrus (AI: 10.5%(8.1%, 13.9%), 14.1%(7.6%, 20.3%), -12.4%(-15.7%, -7.8%), -10.8%(-15.3%, -2.1%) , -12.1%(-17.9%, -6.6%), respectively). Conclusion:The tau network analysis based on 18F-APN-1607 may be used to reveal abnormal topological changes of AD patients, and the tau deposition in the posterior cingulate gyrus, superior parietal gyrus, paracentral lobule, superior temporal gyrus and middle temporal gyrus has obvious laterality in AD patients.

This study investigated the role of netrin-1 in placental vascular development.In vitro rat aortic ring assay and in vivo Matrigel plug assay were conducted to exmaine the effect of netrin-1 on angiogenesis.Human placental microvascular endothelial cells (HPMECs) were isolated and cultured and their viability,migration and tubular formation were studied,in order to examine the effects of netrin-1.The results showed that netrin-1 potently stimulated neovascularization in a mouse Matrigel plug in vivo and the sprouting of endothelial cells in rat aortic rings in vitro.In addition,netrin-1 enhanced the viability,migration and tube formation of HPMECs.Our study suggested that netrin-1 could significantly promote the formation of blood vessels of human placenta and may be a potential target for developing new therapeutic strategies for placental vasculature-related diseases.