Enterovirus A71 (EV-A71) inactivated vaccines have been widely inoculated among children in Kunming City after it was approved. However, there was a large-scale outbreak of Enteroviruses (EVs) infection in Kunming, 2018.The epidemiological characteristics of HFMD and EVs were analyzed during 2008 to 2018, which are before and three years after EV-A71 vaccine starting to use. The changes of infection spectrum were also investigated, especially for severe HFMD in 2018.The incidence of EV-A71 decreased dramatically after EV-A71 vaccine starting use. The proportion of non CV-A16/EV-A71 EVs positive patients raised up to 77.17% to 85.82%, while, EV-A71 and CV-A16 only accounted for 3.41% to 7.24% and 6.94% to 19.42% in 2017 and 2018. CV-A6 was the most important causative agent in all clinical symptoms (Severe HFMD, HFMD, Herpangina and fever), accounting from 42.13% to 62.33%. EV-A71 only account for 0.36% to 2.05%. In sever HFMD, CV-A6 (62.33%), CV-A10 (11.64%), CV-A16 (10.96%) were the major causative agent in 2018. EV-A71 inactivated vaccine has a good protective effect against EV-A71 and induced EVs infection spectrum changefully. EV-A71 vaccine has no or insignificant cross-protection effect on CV-A6, CV-A10 and CV-A16. Herein, developing 4-valent combined vaccines is urgently needed.

Semaphorin 4D (Sema4D) is highly expressed in a variety of tumors and is associated with high invasion, poor prognosis and poor therapeutic response. However, the expression and role of Sema4D in leukemia remains unclear. The present study investigated the expression of Sema4D in pediatric leukemia and its effects in leukemia cells. The results demonstrated that Sema4D protein was highly expressed in peripheral blood mononuclear cells of patients with pediatric leukemia, and high levels of soluble Sema4D were also observed in the plasma of these patients. Sema4D knockdown induced cell cycle arrest in G 0 /G 1 phase, inhibited proliferation and promoted apoptosis in BALL-1 cells, while Sema4D overexpression exhibited the opposite effect. In Jurkat cells, Sema4D knockdown inhibited proliferation and promoted apoptosis, while Sema4D overexpression decreased the abundance of the cells in the G 0 /G 1 phase of the cell cycle and promoted proliferation. Sema4D overexpression also increased the migratory capacity of Jurkat cells and the invasive capacity of BALL-1 cells. The phosphorylation level of PI3K was decreased in both Sema4D knocked-down Jurkat and BALL-1 cells, and the phosphorylation level of ERK was decreased in Sema4D knocked-down BALL-1 cells. The phosphorylation levels of PI3K, ERK and AKT were elevated in patients with pediatric leukemia, and were correlated to the increased Sema4D expression. Sema4D overexpression was associated with a shorter overall survival in patients with acute myeloid leukemia. Overall, the results of the present study indicated that Sema4D serves an important role in leukemia development by activating PI3K/AKT and ERK signaling, and it may be used as a potential target for the diagnosis and treatment of leukemia.

Semaphorin 4D (Sema4D) is highly expressed in various cancers and leukemia. It is involved in the development of acute leukemia. A high level of soluble Sema4D is also present in the plasma of acute leukemia patients. However, it remains unknown whether Sema4D is associated with the clinical characteristics of acute leukemia. In this study, Sema4D expression was examined in peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMCs) of patients with acute leukemia, and it was highly expressed in the PBMCs of B-acute lymphoblastic leukemia (ALL), T-ALL, and acute myeloid leukemia (AML) patients and in the BMMCs of B-ALL and AML patients but not in the BMMCs of T-ALL patients. Sema4D expression was higher in the PBMCs of T-ALL patients than in the PBMCs of B-ALL or AML patients. In addition, Sema4D expression in BMMCs was reduced in B-ALL patients during the chemotherapy process. It was lower in remission patients than in newly diagnosed and patients without remission. In acute leukemia, soluble Sema4D level in serum is positively correlated with Sema4D expression in PBMCs, leukocyte number, and peripheral blast number. Those results suggest that the levels of Sema4D and its soluble form are associated with acute leukemia development and may be regarded as a potential biomarker in pediatric acute leukemia.