Influenza virus is a continuous and severe global threat to mankind.The continuously re-emerging disease gives rise to thousands of deaths and enormous economic losses each year,which emphasizes the urgency and necessity to develop high-quality influenza vaccines in a safer,more efficient and economic way.The influenza subunit and VLP vaccines,taking the advantage of recombinant DNA technologies and expression system platforms,can be produced in such an ideal way.This review summarized the recent advancements in the research and development of influenza subunit and VLP vaccines based on the recombinant expression of hemagglutinin antigen (HA),neuraminidase antigen (NA),Matrix 2 protein (M2) and nucleocapsid protein (NP).It would help to get insight into the current stage of influenza vaccines,and suggest the future design and development of novel influenza vaccines.

Objective: To assess clinical effect and safety of botulinum toxin A injection in external urethral sphincter for male patient with neurogenic detrusor underactivity(DU). Methods: A prospective and self-controlled trail was conducted from August 2012 to October 2017. Male patients with nerve injury, dysuria more than 6 months, DU(bladder contractility index less than 100) were enrolled in this study. Exclusion criteria included patients with acute urinary tract infection, bladder stone, benign prostate hyperplasia, urethral stricture and urethral diverticulum.100 IU BTX-A was dissolved in 4ml normal saline, and the solution of BTX- A was injected into 4 different points(3-o’clock, 6-o’clock, 9-o’clock, and 12-o’clock) in external urinary sphincter with each point of 1ml solution. Patients were evaluated at baseline and 12 weeks after injection. The outcomes included post void residual (PVR), maximum flow rate (Q_max), maximum detrusor pressure during voiding phases (P_det.max), maximum urethral closure pressure (MUCP), the case number of intermittent catheterization (IC)and the score of quality of life (QOL score). Adverse events were also recorded. Results: A total of 58 male patients (all from Guangdong provincial work injury rehabilitation hospital)with mean age 28.6 years suffered from cerebral palsy (n=2), cerebrovascular accident(n=19)and spinal cord injury(n=37) were included into the study. Compared to baseline data, significant difference were observed at week 12 in PVR (56.68 ml vs. 280.11 ml, P<0.001), P_det.max(23.95 cmH₂O vs. 30.01 cmH₂O, P=0.019), Q_max(6.74 ml/s vs. 3.28 ml/s, P=0.042), MUCP(48.25 cmH₂O vs. 79.34 cmH₂O, P<0.001), the case number of IC(40 vs. 58, P<0.001) and QOL score(3.63 vs.5.22, P<0.001) respectively. 5 cases developed perineal pain and 16 cases developed mild transient haematuria. These adverse events were disappeared by medical symptomatic treatment during 3-5 days. Conclusions BTX-A externalurethral sphincter injections help reduce urethra resistance and also improve the quality of life for patients with neurogenic detrusor underactivity.