Effectiveness of fecal DNA syndecan-2 methylation testing for detection of colorectal cancer in a high-risk Chinese population

BACKGROUND Colorectal cancer(CRC)is among the most prevalent and life-threatening malignancies worldwide.Syndecan-2 methylation(mSDC2)testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples.Cancer(CRC)is among the most prevalent and life-threatening malignancies worldwide.mSDC2 testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples.AIM To validate the effectiveness of fecal DNA mSDC2 testing in the detection of CRC among a high-risk Chinese population to provide evidence-based data for the development of diagnostic and/or screening guidelines for CRC in China.METHODS A high-risk Chinese cohort consisting of 1130 individuals aged 40-79 years was selected for evaluation via fecal mSDC2 testing.Sensitivity and specificity for CRC,advanced adenoma(AA)and advanced colorectal neoplasia(ACN)were determined.High-risk factors for the incidence of colorectal lesions were determined and a logistic regression model was constructed to reflect the efficacy of the test.RESULTS A total of 1035 high-risk individuals were included in this study according to established criteria.Among them,16 suffered from CRC(1.55%),65 from AA(6.28%)and 189 from non-AAs(18.26%);150 patients were diagnosed with polyps(14.49%).Diagnoses were established based upon colonoscopic and pathological examinations.Sensitivities of the mSDC2 test for CRC and AA were 87.50%and 40.00%,respectively;specificities were 95.61%for other groups.Positive predictive values of the mSDC2 test for CRC,AA and ACN were 16.09%,29.89%and 45.98%,respectively;the negative predictive value for CRC was 99.79%.After adjusting for other high-risk covariates,mSDC2 test positivity was found to be a significant risk factor for the occurrence of ACN(P<0.001).CONCLUSION Our findings confirmed that offering fecal mSDC2 testing and colonoscopy in combination for CRC screening is effective for earlier detection of malignant colorectal lesions in a high-risk Chinese population.

奥洛他定联合卡介菌多糖核酸对慢性荨麻疹患者的免疫应答机制探讨

目的研究奥洛他定联合卡介菌多糖核酸治疗前后慢性荨麻疹患者Toll样受体2(TLR2)表达量的变化及其与免疫球蛋白E(IgE)、补体C3、补体C4、细胞因子含量的相关性。方法选取2016年1月-2016年11月在佛山市中医院接受奥洛他定联合卡介菌多糖核酸治疗的慢性荨麻疹患者作为研究对象。治疗前和治疗后2、4及6周时,采集外周血并测定TLR2、TLR4、TLR7、TLR9的表达量,采集血清并测定IgE、C3、C4、Th1、Th2细胞因子的含量。结果治疗后2、4及6周时,外周血单个核细胞中TLR2的mRNA含量均低于治疗前,TLR4、TLR7及TLR9的mRNA含量与治疗前比较,差异无统计学意义(P>0.05);血清中IgE、白细胞介素4(IL-4)、白细胞介素10(IL-10)的含量均低于治疗前,C3、C4、IFN-γ、白细胞介素2(IL-2)的含量高于治疗前;外周血中TLR2的表达量与血清中IgE、IL-4、IL-10的含量呈正相关,与C3、C4、IFN-γ、IL-2的含量呈负相关。结论奥洛他定联合卡介菌多糖核酸治疗可能通过TLR2通路调节慢性荨麻疹患者体内的免疫应答。

Characterization of inflammatory factor-induced changes in mesenchymal stem cell exosomes and sequencing analysis of exosomal microRNAs

BACKGROUND Treatments utilizing stems cells often require stem cells to be exposed to inflammatory environments,but the effects of such environments are unknown.AIM To examine the effects of inflammatory cytokines on the morphology and quantity of mesenchymal stem cell exosomes(MSCs-exo)as well as the differential expression of microRNAs(miRNAs)in the exosomes.METHODS MSCs were isolated from human umbilical tissue by enzymatic digestion.Exosomes were then collected after a 48-h incubation period in a serum-free medium with one of the following the inflammatory cytokines:None(control),vascular cell adhesion molecule-1(VCAM-1),tumor necrosis factor(TNF)α,and interleukin(IL)6.The morphology and quantity of each group of MSC exosomes were observed and measured.The miRNAs in MSCs-exo were sequenced.We compared the sequenced data with the miRBase and other non-coding databases in order to detect differentially expressed miRNAs and explore their target genes and regulatory mechanisms.In vitro tube formation assays and Western blot were performed in endothelial cells which were used to assess the angiogenic potential of MSCs-exo after inflammatory cytokine stimulation.RESULTS MSCs-exo were numerous,small,and regularly shaped in the VCAM-1 group.TNFαstimulated MSCs to secrete larger and irregular exosomes.IL6 led to a reduced quantity of MSCs-exo.Compared to the control group,the TNFαand IL6 groups had more downregulated differentially expressed miRNAs,particularly angiogenesis-related miRNAs.The angiogenic potential of MSCs-exo declined after IL6 stimulation.CONCLUSION TNFαand IL6 may influence the expression of miRNAs that down-regulate the PI3K-AKT,MAPK,and VEGF signaling pathways;particularly,IL6 significantly down-regulates the PI3K-AKT signaling pathway.Overall,inflammatory cytokines may lead to changes in exosomal miRNAs that abnormally impact cellular components,molecular function,and biological processes.

Three-dimensional characteristics of Fe-rich intermetal ics in gravity-cast Al-6Si alloys

Fe-rich intermetallics, especially β-Fe phase, usually forming in the microstructure of cast aluminum alloys, are very detrimental to mechanical properties. In the present work, the effects of Fe content on phase transformation and microstructures were analyzed using a 3D X-ray microscope. Based on the highresolution 3D X-ray computed tomography, the 3D characteristics of Fe-rich intermetallics and micropores in the gravity-cast Al-6 Si alloys with different Fe contents were investigated. In addition, the effect of intermetallics on the microporosity was discussed. The results show that with increasing the Fe content from 0.10 wt.% to 0.60 wt.%, the volume fraction of Fe-rich intermetallics and the volume of the largest size Fe-rich intermetallic increased, and the 3D morphology of intermetallics changed from fine flake to network aggregation. As the Fe contents increased, the shrinkage pores were characterized, which were rather complex due to the micropores promoted by the intermetallics interactions.

Seven-frequency VLBI Observations of the GHz-Peaked-Spectrum Source OQ 208

We present quasi-simultaneous VLBI images of the GHz-Peaked-Spectrum radio source OQ 208 obtained with the Very Long Baseline Array at 1.4, 1.7, 2.3, 5.0, 8.4, 15.4 GHz and the European VLBI Network at 6.7 GHz. The low frequency （1.4, 1.7 and 2.3 GHz） observations reveal a weak and extended steep-spectrum component at about 30 mas away at position angle - 110°, which may be a remnant emission. The radio structure of OQ 208 consists of two mini-lobes at 5.0, 6.7, 8.4 and 15.4 GHz. Our spectral analysis further confirms that the southwest lobe undergoes free-free absorption and finds that the free-free absorption is stronger in the inner region. By fitting the 8.4 GHz images from 1994 to 2005, we obtain a separation speed of 0.0314-0.006 mas yr^-1 between the two mini-lobes. This indicates a jet proper motion of 0.1054-0.020 c and a kinematic age of 219±42 yr for the radio source.

Efficient and Divergent Synthesis of Medium-Sized Lactams through Zinc-Catalyzed Oxidative Cyclization of Indoly Ynamides

An efficient zinc-catalyzed oxidative cyclization of readily available indoly ynamides has been developed,enabling rapid and practical access to a diverse array of valuable medium-sized lactams in mostly good to excellent yields with wide substrate scope.In addition,such an asymmetric synthesis has also been explored by employing the chiral substrate.

Copper-Catalyzed Carbocyclization of Silyl Enol Ether Tethered Ynamides for Efficient and Practical Synthesis of 2-Azabicyclo[3.2.o] Compounds

Summary of main observation and conclusion An efficient copper-catalyzed carbocyclization of silyl enol ether tethered ynamides has been developed,allowing rapid and practical construction of diverse 2-azabicyclo[3.2.0]compounds in generally good to excellent yields with broad substrate scope under mild reaction conditions.Importantly,this protocol not only constitutes a rare example of non-noble metal-catalyzed alkyne carbocyclization,but also represents a rare cyclization on the B-position ofπu-tethered ynamides.The possibility of asymmetric carbocyclization via kinetic resolution also emerges.