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OBJECTIVES@#To study the biological processes and functions of serum exosomes in children in the acute stage of Kawasaki disease (KD), so as to provide new biomarkers for the early diagnosis of KD.@*METHODS@#In this prospective study, 13 children with KD who were treated in Children's Hospital of Soochow University from June 2019 to August 2020 were enrolled as the KD group, and 13 children who were hospitalized due to bacterial infection during the same period were enrolled as the control group. Whole blood was collected on the next morning after admission, serum samples were obtained by centrifugation, and exosomes were extracted through ultracentrifugation. Serum exosomes were analyzed by label-free quantitative proteomics, and differentially expressed proteins (DEPs) were screened out for functional enrichment analysis. A protein-protein interaction (PPI) network was plotted, and unique proteins were validated by targeted proteomics.@*RESULTS@#A total of 131 DEPs were screened out for the two groups, among which 27 proteins were detected in both groups. There were 48 unique DEPs in the KD group, among which 23 were upregulated and 25 were downregulated, and these proteins acted on "complement and coagulation cascades" and "the MAPK signaling pathway". Validation by targeted proteomics showed that FGG, SERPING1, C1R, C1QA, IGHG4, and C1QC proteins were quantifiable in the KD group. A total of 29 proteins were only expressed in the control group, among which 12 were upregulated and 17 were downregulated. Four proteins were quantifiable based on targeted proteomics, i.e., VWF, ECM1, F13A1, and TTR. A PPI network was plotted for each group. In the KD group, FGG and C1QC had close interaction with other proteins, while in the control group, VWF had close interaction with other proteins.@*CONCLUSIONS@#The serum exosomes FGG and C1QC in children in the acute stage of KD are expected to become the biomarkers for the early diagnosis of KD. For children with unexplained fever, detection of FGG, C1QC1, and VWF may help with etiological screening.
Subject(s)
Child , Humans , Biomarkers , Exosomes , Extracellular Matrix Proteins , Mucocutaneous Lymph Node Syndrome/diagnosis , Prospective Studies , Proteomics , von Willebrand FactorABSTRACT
Triptolide (TP), an active component of Tripterygium wilfordiiHook. f. (TWHF), has been widely used for centuries as a traditional Chinese medicine. However, the clinical application of TP has been restricted due to multitarget toxicity, such as hepatotoxicity. In this study, 28 days of oral TP administration (100, 200, or 400 μg·kg
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Objective To analyze the imaging feature and misdiagnosis reason of pancreatic neuroendocrine neoplasm (pNEN) with pancreatic duct obstruction. Methods The data of 25 patients with pNEN accompanied by pancreatic duct obstruction who underwent surgical treatment in our hospital from Jun. 2012 to Oct. 2018 were retrospectively analyzed. The imaging findings and misdiagnosis reason of pNEN were summarized by two senior radiologists. Results A total of 26 lesions in 25 patients were included, including six G1 tumors, 19 G2 tumors and one G3 tumor. The average size of the lesions was (2.5±1.7) cm (range, 0.4-9.1 cm). Of the 26 lesions, the main pancreatic duct was mildly dilated in 12 cases (46.2%), moderately dilated in eight cases (30.8%), and severely dilated in six cases (23.1%). Seventeen (65.4%) lesions were accompanied by severe atrophy of the upstream pancreatic parenchyma, six (23.1%) by moderate atrophy, one (3.8%) by mild atrophy, and two (7.7%) with no atrophy. Before operation, 14 (53.8%) lesions were correctly diagnosed as pNEN; and eight (30.8%) lesions were misdiagnosed as pancreatic cancer, two (7.7%) as solid pseudopapillar tumor, one (3.8%) as intraductal papillary mucinous neoplasm and one (3.8%) as serous cystadenoma. The main reasons of misdiagnosis included atypical lesion manifestations, insufficient understanding of atypical manifestations of the disease, inadequate observation of image details, less consideration of clinical data of the patients, etc. Conclusion It is difficult to differentiate pNEN with pancreatic duct obstruction from other pancreatic tumors. Being familiar with the atypical manifestations of the lesion, observing the image details carefully and understanding clinical data with imaging findings can help to reduce misdiagnosis and improve the accuracy of diagnosis.
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<p><b>OBJECTIVE</b>To evaluate the anticoagulant and antineoplastic activities of chemically modified low-molecular-weight heparin (LMWH).</p><p><b>METHODS</b>LMWH obtained by splitting unfractionated heparin (UFH) with sodium periodate oxidation and sodium borohydride reduction was subjected to acetylation catalyzed by DCC and DMAP to produce acetylated LMWH (ALMWH). The anticoagulant activity of ALMWH was determined in mice, and its antiproliferative and anti-invasion activities was assessed in human breast cancer cells MDA-MB-231 and MFC-7.</p><p><b>RESULTS</b>The anticoagulant activity of LMWH was decreased significantly after acetylation. The concentrations of commercial LMWH* and ALMWH for doubling the coagulation time (CT) were 33.04 µmol/L and 223.56 µmol/L, respectively, and the IC(50) of ALMWH for doubling CT was 6 times of that of LMWH*. ALMWH and LMWH at 0.1, 0.3, 0.9, 2.7 and 8.1 mmol/L both significantly inhibited the proliferation of MDA-MB-231 and MCF-7 cells in a concentration-dependent manner, but ALMWH produced stronger inhibitory effects. The IC(50) of LMWH and ALMWH for inhibiting cell proliferation was 3168.4 µmol/L and 152.6 µmol/L in MCF-7 cells, and 12299.6 µmol/L and 22.2 µmol/L in MDA-MB-231 cells, respectively. ALMWH and LMWH all markedly suppressed the invasion of MDA-MB-231 cells with comparable effects.</p><p><b>CONCLUSION</b>Chemical modification of structure can endow LMWH with a low anticoagulant and high antiproliferative activities.</p>