Objective To analyze the epidemiological characteristics of the severe cases of hand , foot and mouth disease ( HFMD) in Danzhou and to provide a scientific evidence for the prevention of severe HFMD.Methods Descriptive epidemiological analysis was used to analyze the characteristics of severe ca -ses of HFMD occurred from 2010 to 2014 .Results A total of 18 960 cases of HFMD were reported in Danzhou City from 2010 to 2014.The death rate (annual deaths/1000 persons) was 0.13%.One hundred and eighty-eight cases (0.99%) were diagnosed as severe HFMD with a male to female ratio of 2.4 :1 and 96.28%of them were scattered inhabiting children .Six cases were died from severe HFMD and all of them were under 2 years of age.In total 87.77%of the severe cases were occurred in children under 2 years of age.The severe cases were mainly occurred in June and July .Children form the countryside showed higher rates of severe HFMD than those from cities and towns .No significant differences in the time between the in-itial diagnosis and treatment for children with HFMD in countryside and urban areas were found .However , the differences in the duration from initial diagnosis to severe HFMD between children in countryside and ur -ban areas were statistically significant (M-W test, P<0.05).Among the 188 severe cases, 82.44% were initially diagnosed as common HFMD cases by the county-level medical institutions and 90.96%were diag-nosed as severe cases by the municipal and above medical institutions .The cases positive for EV71 strains accounted for 44.15%.Conclusion Most of the severe HFMD were developed in scattered inhabiting chil-dren under 2 years of age in the countryside of Danzhou during 2010 to 2014.In order to decrease the mor-bidity and mortality of severe HFMD in children , it is necessary to implement health education for residents , to improve the professional skills of medical staffs in the early diagnosis of HFMD , and to strengthen etiologi-cal surveillances and warning system for HFMD .

In this report, a series of novel piperidine-substituted thiophene[3,2-]pyrimidine derivatives were designed to explore the hydrophobic channel of the non-nucleoside reverse transcriptase inhibitors binding pocket (NNIBP) by incorporating an aromatic moiety to the left wing of the lead . The newly synthesized compounds were evaluated for anti-HIV potency in MT-4 cells and inhibitory activity to HIV-1 reverse transcriptase (RT). Most of the synthesized compounds exhibited broad-spectrum activity toward wild-type and a wide range of HIV-1 strains carrying single non-nucleoside reverse transcriptase inhibitors (NNRTI)-resistant mutations. Especially, compound exhibited the most potent activity against wild-type and a panel of single mutations (L100I, K103N, Y181C, Y188L and E138K) with an EC ranging from 6.02 to 23.9 nmol/L, which were comparable to those of etravirine (ETR). Moreover, the RT inhibition activity, preliminary structure-activity relationship and molecular docking were also investigated. Furthermore, exhibited favorable pharmacokinetics (PK) profiles and with a bioavailability of 33.8%. Taken together, the results could provide valuable insights for further optimization and compound holds great promise as a potential drug candidate for the treatment of HIV-1 infection.