icating that Fas/FasL plays an impertant role in the regulation of immune/inflammation response in the CNS, and such role does not depend on the apoptotic pathway, This article reviews its progress in research on the inflammatory response in the CNS.

Scavenger receptor CD36 could bind and endocytose oxLDL into macrophages which were then differentiated into foam cells that constitute the atherosclerotic lesion core, and was considered to be a potential target to treat atherosclerosis. In the establishment of the compound library of berberine (BBR, 1) analogues, we discovered that 13-hexylberberine (2) showed an antagonistic activity against CD36. Taking 2 as the lead compound, 21 derivatives were synthesized and their antagonistic activities were evaluated via an ELISA-like high-throughput screening (HTS) model. The primary structure-activity relationships were studied. It was indicated that the introduction of suitable groups at the 2- and 3-position of the aromatic ring A or at the 9-position of the aromatic ring D could enhance the activity. Among the 21 studied compounds, 7g bearing a benzyloxyl group at the 9-position provided a highest CD36 antagonistic activity with the IC50 value of 7.7 micromol L(-1). Besides, its antagonistic activity was further verified with Sf9 insect cell HTS model. So berberine analogues are a new family of CD36 receptor antagonists and worthy to be studied further.

LPS stimulation of macrophages production of IFN-beta plays a key role in innate immunity defending the microbial invasion. In this study, the effect of S632A3 promoting LPS-induced IFN-beta production and the underlying mechanism were investigated, mRNA level was measured by real-time PCR, cytokine production was determined by ELISA, GSK-3beta activity was investigated by kinase assay, protein phosphorylation and expression were evaluated by Western blotting. The results revealed that S632A3 significantly augmented IFN-beta production by LPS-stimulated macrophages. S632A3 inhibition of the activation of GSK-3beta, reduced the threonine 239 phosphorylation of transcription factor c-Jun but increased the total level of c-Jun in LPS-stimulated macrophages. Moreover, small interfering RNA-mediated knockdown of c-Jun level abrogated the ability of S632A3 to augment IFN-beta. The study thus demonstrates S632A3 being a new anti-inflammation lead compound and provides a molecular mechanism by which S632A3 promoted LPS-induced IFN-beta production in macrophages through inhibiting the activation of GSK-3beta.

Aim To investigate the induction of endothelial cell apoptosis and the suppression of VEGF expression in cancer cells by sodium caffeate (SCA). Methods Apoptosis of transformed human umbilical vein endothelial cells (ECV304 cell line) was detected by flow cytometry, DNA electrophoresis assay and morphological assessment. Western blotting analysis was applied for determination of VEGF expression in cancer cells. Substrate degradation by type Ⅳ collagenase was measured by zymography.ELISA was used to detect the binding of type Ⅳ collagenase with relevant monoclonal antibody. Results SCA induced ECV304 cell apoptosis in a time- and dose-dependent manner. After treatment with 100 and fluorescence and distinct changes of nuclear morphology, such as pyknosis and the occurrence of apoptotic bodies. VEGF expression in hepatoma HepG-2 cells and prostate carcinoma DU145 cells was reduced after SCA treatment. The degradation activity of type Ⅳ collagenase including MMP-2 and MMP-9 secreted by giant cell pulmonary carcinoma PG cells was inhibited by SCA in a dose-dependent manner. SCA also reduced the binding of mAb 3D6, a relevant monoclonal antibody, to type Ⅳ collagenase. Conclusion SCA can induce endothelial cell apoptosis and inhibit VEGF expression as well as type Ⅳ collagenase activity in cancer cells. SCA might be active in modulating tumor angiogenesis and the microenvironment.

Objective To evaluate cerebral parenchymal atrophy of patients with Alzheimer's disease(AD)through the compara-tive analysis of the volume and morphology of the brain ventricle between patients with AD and normal elderly.Methods 20 patients with AD and 20 normal elderly people were scanned at 3.0T MR,and lateral ventricle section images were achieved,and the lateral ventricle volume and the anterior horn,posterior horn and temporal horn of the lateral ventricle were calculated by analyzing the re-construction of section images with MIMICS software from Belgian.Results As compared with normal elderly group,the patients with AD exhibited significantly increased the volume of left ventricular volume(LV),right ventricular volume (RV)and total vol-ume (TV)(P<0.05).Angle of bilateral anterior horn and temporal horn but not posterior horn of the lateral ventricle in patients with AD were significantly higher than that in normal elderly (P<0.05).The volume of the left,right and total cerebral ventricle, the angle of the anterior horn of the left and right lateral ventricle and the angle of the temporal horn of the left and right lateral ven-tricle were negatively correlated with MMSE (P<0.05).Conclusion Patients with AD exhibites significantly greater volume and an-gle of the lateral ventricular than normal elderly people.These related data measured can predict brain parenchymal atrophy of pa-tients with AD more conveniently and accurately.

To explore the effects of pre-pregnancy body mass index (BMI), weight gain and blood lipid level during pregnancy on pregnancy outcome in patients with and without gestational diabetes mellitus(GDM). A total of 12 650 singleton pregnant women without history of hypertension and diabetes who were admitted at Women's Hospital, Zhejiang University School of Medicine for delivery from January 2018 to April 2019 were enrolled in the study. There were 2381 cases complicated with gestational diabetes (GDM group) and 10 269 cases without GDM (non-GDM group). The pre-pregnancy BMI and weight gain during pregnancy were documented in two groups. The factors related to perinatal outcome were analyzed. In both GDM and non-GDM pregnant women, pre-pregnancy overweight and excessive weight gain during pregnancy were independent factors of large for gestational age infant (LGA), small for gestational age infant (SGA) and first cesarean section (<0.01 or <0.05). Excessive weight gain during pregnancy was also an independent risk factor of preeclampsia (<0.05). Triglyceride levels in the second trimester were independently associated with multiple adverse pregnancy outcomes, such as LGA, preeclampsia, initial cesarean delivery, premature delivery. Controlling excessive or insufficient weight gain during pregnancy can significantly reduce the incidence of LGA and SGA. And controlling BMI before pregnancy can effectively reduce the incidence of LGA, preeclampsia and the first cesarean section. For non-GDM pregnant women, abnormal blood lipid levels in the second trimester may be closely related to multiple adverse pregnancy outcomes, and active dietary guidance or treatment is also required.
Body Mass Index ; Cesarean Section ; Diabetes, Gestational/epidemiology* ; Female ; Humans ; Lipids ; Pregnancy ; Pregnancy Outcome ; Weight Gain

OBJECTIVE: To explore the genetic basis of a child with holoprosencephaly. METHODS: Genomic DNA of the child was extracted and subjected to whole exome sequencing. Suspected variant was verified by Sanger sequencing of her family members. RESULTS: Cranial MRI suggested lobulated holoprosencephaly with partial absence of corpus callosum. Genetic testing revealed that she has carried a heterozygous c.517C>G (p.His173Asp) variant of the SIX3 gene, for which both of her parents were of wild type. Based on the American College of Medical Genetics and Genomics guidelines, the c.517C>G variant of SIX3 gene was predicted to be pathogenic (PS2+PM1+PM2+PM5+PP3). CONCLUSION The SIX3 gene c.517C>G variant probably underlay the multiple malformations in this child. Above finding has enabled her definite diagnosis.
Child ; Family ; Female ; Heterozygote ; Holoprosencephaly/genetics* ; Humans ; Mutation ; Whole Exome Sequencing

To investigate the effect of dietary fiber on blood glucose and pregnancy outcomes in patients with gestational diabetes mellitus (GDM). One hundred and twelve patients with GDM in the second trimester of pregnancy were recruited from Women's Hospital, Zhejiang University School of Medicine. Patients were randomized into two groups with 56 in each group: the control group received basic nutrition support; while the dietary fiber group were given additional dietary fiber ( total dietary fiber per day) before meals in addition to basic nutrition support. Intervention for all cases lasted for 8 weeks. Fasting blood glucose and postprandial blood glucose (2 h BG) were measured every week, and oral glucose tolerance test (OGTT) was performed at 42 d postpartum to evaluate the glycemic outcomes. Perinatal outcomes were recorded. The dietary fiber intervention markedly improved 2 h BG in patients with GDM and significantly elevated the glucose compliance rate from the 3rd to 8th week compared to the control group ( <0.05 or <0.01). OGTT 2 h glucose and the incidence of impaired glucose tolerance in the dietary fiber group were significantly lower than those in the control group, while the glucose compliance rate was significantly higher than that in the control group (all <0.01). Moreover, the rates of adverse perinatal outcomes, such as premature rupture of membranes and neonatal hyperbilirubinemia were declined in the dietary fiber group (<0.05 or <0.01). Dietary fiber intervention can ameliorate hyperglycemia in GDM patients, improve perinatal outcomes and reduce the incidence of postpartum impaired glucose tolerance.
Blood Glucose ; Diabetes, Gestational ; Dietary Fiber ; Female ; Glucose Tolerance Test ; Humans ; Infant, Newborn ; Pregnancy ; Pregnancy Outcome

OBJECTIVETo reduce the acquisition time of carotid high-resolution contrast-enhanced magnetic resonance imaging (CEMRI), we designed a small field-of-view (FOV) quadruple-inversion-recovery (SF-QIR) T1WI and evaluated the image quality.

METHODSTwenty-four subjects with carotid plaque were enrolled in our study. All the subjects were imaged using the same 3.0T MRI by SF-QIR and standard rectangular FOV QIR (SrF-QIR) with identical parameters except for the phase-encoding step numbers and the RF excitation methods. Three independent readers qualitatively evaluated the differences between the two sequences in regard of the carotid outer wall border delineation, fibrous cap and lipid-rich necrotic core (LR-NC) border delineation, and diagnostic confidence. The quantitative measurements included maximal stenosis, wall area, LR-NC area, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). The inter-reader variability was assessed.

RESULTSThe application of SF-QIR combined with orthogonal radio frequency excitation resulted in nearly half of the scan time with the SrF-QIR. Both qualitative and quantitative assessment by the readers revealed no significant differences between the two sequences except for SNR and CNR (Pgt;0.05). Since the mean loss of SNR with SF-QIR was 37.7%, SrF-QIR demonstrated a superior performance in SNR (P<0.001).

CONCLUSIONThe small FOV QIR sequence is effective in high-resolution CEMRI for evaluating carotid plaques and can effectively reduce the scan time and eliminate motion artifacts.

Adult ; Aged ; Aged, 80 and over ; Carotid Artery Diseases ; diagnosis ; pathology ; Female ; Humans ; Image Enhancement ; methods ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged

OBJECTIVETo assess the value of high-resolution three-dimensional black-blood magnetic resonance imaging (3D-BB-MRI) in quantitative measurement of carotid atherosclerotic plaque by comparison with two-dimensional black-blood magnetic resonance imaging (2D-BB-MRI).

METHODSForty patients were scanned with routine 2D and oblique-sagittal 3D-BB-MRI. The original oblique-sagittal 3D images were reformatted to an axial 2D-like dataset. Two experienced radiologists identified the interested slice in consensus for every patient (unilateral carotid artery) in 2D-BB-MRI images and matched the axial reformatted 3D images with 2D black-blood images. Plaque thickness (PT), lumen area (LA) and total vessel area (TVA) were measured, and lumen stenosis (LS) and normalized wall index (NWI) were calculated.

RESULTSThere was no measurement difference between 2D-BB-MRI and reformatted 3D-BB-MRI (P>0.05), and these two methods had a good correlation (r<0.9). The Bland-Altman chart showed that 2D-BB-MRI and 3D-BB-MRI were in good agreement in the measurement of PT, LA and TVA.

CONCLUSION3D-BB-MRI and 2D-BB-MRI have no obvious difference in quantitative measurement of the carotid plaques. 3D-BB-MRI can demonstrate the vessels and plaques by multiplanar reconstruction and thus have better performance in evaluating carotid atherosclerosis compared with 2D-BB-MRI.

Adult ; Aged ; Aged, 80 and over ; Carotid Artery Diseases ; pathology ; Female ; Humans ; Imaging, Three-Dimensional ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged