Objective To understand the potential risk for schistosomiasis transmission caused by introduction of infection source from mobile population in Shanghai. Methods Field investigation was conducted in the suburb of Shanghai City by screening the mobile population living in Shanghai for more than 1 month and over 1 years old in a procedure of interviewing, serum indirect hemagglutination (IHA) test, and then fecal examination to detect the eggs with nylon sedimentation approach for those IHA positives. Results Among 2 931 mobile people investigated, 1 575 were male (53.74%) and 1 356 were female(46.26%); 138 out of 2 931 were positive in IHA test (4.71%). 1 938 (66.12%) out of 2 931 came from Schistosoma japonicum-endemic provinces and its positive rate in mobile population (5.99%) was significantly higher than those from the transmission-interrupted provinces (2.6%) (?2=10.28, P

Objective: To explore the role of iTr35 cells in the pathogenesis of children with pulmonary artery hypertension (PAH) in children, and the percentage of iTr35 cells and serum interleukin(IL)-35 levels in peripheral blood of patients with PAH were investigated.Their inhibitory effects on the expression of vascular cell adhesion molecule-1 (VCAM-1) on vascular endothelial cells were also analyzed. Methods: After 3 mL peripheral blood of 30 congenital heart disease (CHD) patients with PAH, 22 CHD patients without PAH and 30 age or gender matched healthy controls (HC) were collected, the percentage of iTr35 cells were detected by flow cytometry and the concentrations of serum IL-35 were detected by Luminex, as well as soluble VCAM-1 (sVCAM-1). Human pulmonary artery endothelial cells (HPAECs) were cultured in vitro and divided into control group, tumor necrosis factor (TNF)-α group and IL-35+ TNF-α group.The expression of VCAM-1 and nuclear factor(NF)-κB P65 protein of each group were detected by flow cytometry and Western blot.The adhesion of peripheral blood mononuclear cells (PBMCs) to HPAECs was observed by fluorescence microscope. Results: Compared to CHD patients without PAH, the percentage of iTr35 cells[0.86(0.45-1.63)% vs.1.14(0.46-2.11)%](H=20.52, P<0.05) in peripheral blood and serum IL-35 levels[2.43(1.76-2.85) μg/L vs.3.17(2.92-5.66) μg/L](H=119.56, P<0.05) were significantly decreased in CHD patients with PAH.However, serum sVCAM-1 concentration[923.1(892.6-1 118.7) μg/L vs.776.1(743.5-932.3) μg/L ] in CHD patients with PAH were significant increased (H=65.65, P<0.05). In addition, the concentration of serum IL-35 were negatively correlated with sVCAM-1 in PAH patients (r=-0.374 P=0.042). In vitro, the positive rate of VCAM-1 on HPAECs was significant decreased in IL-35+ TNF-α group as compared to the TNF-α group [(2.07±0.82)% vs.(5.83±1.34)%, F=1 197.18, P<0.05]. In addition, the protein expression of NF-κB P65 in HPAECs was significantly decreased in TNF-α+ IL-35 group as compared to TNF-α group, as well as the adhesion of PBMCs to HPAECs (F=212.04, 2 533.51, all P<0.05). Conclusions The percentages of iTr35 and levels of IL-35 are reduced in the peripheral blood of patients with PAH.Through in vitro experiments, IL-35 is found to reduce PBMCs adhesion by inhibiting VCAM-1 expression in HPAECs.

Objective:Molecular mechanisms underlying compound heterozygous mutations in a patient with inherited antithrombin (AT) deficiency.Methods:The proband was admitted to the First Affiliated Hospital of Wenzhou Medical University in November 2018 with a one-day history of sudden syncope and limb twitching. Peripheral venous blood was collected from the proband and members of his lineages, totaling nine persons across three generations, and a family lineage survey was conducted. AT activity (AT:A) was measured using a chromogenic substrate assay, while AT antigen (AT:Ag) was detected through an immunoturbidimetric assay. Mutation sites were identified by means of Sanger sequencing of the SERPINC1 gene, and silico tools were applied to predict the mutational conservation and hydrophobicity changes. Recombinant plasmid expression vectors were constructed and transfected into HEK293T cells for in vitro overexpression studies. The recombinant AT protein was characterized using Western Blotting, ELISA, and cellular immunofluorescence assays.Results:The proband was a 21-year-old man with type Ⅰ AT deficiency. His AT:A was 33%, along with a corresponding reduction in AT:Ag. The genetic analysis revealed there was a heterozygous insertion mutation at c.318_319insT (p.Asn107*) and a heterozygous missense mutation at c.922G>T (p.Gly308Cys) in exons 2 and 5, respectively. These mutation sites were entirely conserved among the homologous species. Additionally, hydrophobicity studies showed that the p.Gly308Cys mutation will decrease the hydrophilicity of amino acid residues 307-313. The in vitro expression studies indicated a reduction of approximately 46.98%±2.94% and 41.35%±1.48% in the amount of recombinant protein AT-G308C in transfected cell lysates and culture supernatants, respectively. Treatment with the proteasome inhibitor (MG132) restored the cytoplasmic levels of AT-G308C protein to a level similar to that of wild-type protein. However, neither cell lysate nor culture supernatant demonstrated the presence of the recombinant protein AT-N107*. Conclusions:The heterozygous insertion mutation of p.Asn107* and the heterozygous missense mutation of p.Gly308Cys have been associated with reduced AT levels in proband. The p.Asn107* heterozygous insertion mutation may initiate the degradation of mRNA via nonsense mutation-mediated mechanisms, which would remove the defective transcripts, as well as the p.The Gly308Cys heterozygous missense mutation may cause the AT protein to undergo proteasome-dependent degradation by modifying the hydrophobicity of nearby residues in the cytoplasm.