Background: Postoperative adjuvant steroid therapy is regarded as the conventional treatment for patients with biliary atresia (BA) who have undergone Kasai portoenterostomy (KP). However, whether the steroid therapy can improve BA outcomes is controversial. This meta-analysis aimed to evaluate the effects of adjuvant steroid therapy on the surgical prognosis of BA.Methods: We searched related studies published in PubMed, Embase, Web of Science, Cochrane, and the Chinese National Knowledge Infrastructure database up to May 2022. Data on the effect of steroid use on the clinical prognosis of the patients, including the jaundice clearance rate (JCR), native liver survival rate (NLSR) at 6, 12, and 24 months after KP, and the incidence of cholangitis, were extracted. Subgroup analyses based on age at KP, administration method, initial dosage, and steroid type were conducted. Statistical analysis was conducted using Stata/SE 12.0.Results: Eleven articles (a total of 1,032 patients) were included in the present meta-analysis. The results demonstrated that postoperative adjuvant steroid therapy improved JCR at the 6/12/24-month follow-up (RR: 1.35, 95% CI: 1.18–1.55, p < 0.001; RR:1.49, 95% CI, 1.12–1.99, p = 0.006; RR: 1.41, 95% CI: 1.14–1.75, p = 0.002) and improved NLSR at the 24-month follow-up (RR: 1.31, 95% CI: 1.03–1.68, p = 0.028). However, steroids could not significantly improve NLSR at the 6/12-month follow-up (RR: 1.06; 95% CI: 0.98–1.15; p = 0.17; RR: 1.22; 95% CI: 0.97–1.54; p = 0.095), and might not decrease the incidence of postoperative cholangitis (RR: 0.78, 95% CI: 0.60–1.01, p = 0.058). Furthermore, subgroup analyses confirmed that three variables (age at KP, administration method, and initial dosage) could affect the efficacy of steroids in BA patients.Conclusion: Postoperative adjuvant steroid therapy can significantly improve bile flow. The superiority of steroid therapy was more remarkable in patients aged ≤70 days at KP than in those aged >70 days. Additionally, intravenous followed by oral steroid administration method and medium initial dosage seemed to have the more reliable efficiency on bile flow. And patients treated by steroid had better long-term (24-month) native liver survival, but there is no significant effect on short-term native liver survival and postoperative cholangitis. Further studies are warranted.

Objectives Phage therapy has shown a great promise for the treatment of multidrug-resistant bacterial infections. However, the lack of a thorough and organized understanding of phage-body interactions has limited its clinical application. Methods Here, we administered different purified phages (Salmonella phage SE_SZW1, Acinetobacter phage AB_SZ6, and Pseudomonas phage PA_LZ7) intravenously to healthy animals (rats and monkeys) to evaluate the phage-induced host responses and phage pharmacokinetics (PK) with different intravenous (IV) doses in healthy animals. The plasma and the organs were sampled after different IV doses to determine the phage biodistribution, the phage-induced cytokines, and antibodies. The potential side effects of phages on animals were assessed. Results A non-compartment model revealed that the plasma phage titer gradually decreased over time following a single dose. Repeated doses caused that the plasma phage titer at 5 minutes dropped 2-3 Log10 compared to the first dose regardless of phage types in rats. Host innate immune responses were activated including the upregulated expression (>10-fold) of TNF-α and splenic enlargement following repeated doses. Phage-specific neutralization antibodies in animals receiving phages were detected. Similar results were obtained from monkeys. Conclusions The mammalian bodies were well-tolerant to the administered phages. The animal responses to the phages and the phage biodistribution profiles could have a significant impact on the efficacy of phage therapy.

Pseudomonas aeruginosa is a leading cause of hospital-acquired infections, and the emergence of multi-drug resistant strains has prompted the search for alternative treatments such as phage therapy. In this study, we combined host range and genomic information to design a four-phage cocktail that effectively killed several clinical strains (79%, 23/29) of P. aeruginosa. We demonstrated that the cocktail, composed of three novel phages (PA_ZH1, PA_GL1, and PA_CQ9) and one previously characterized phage (PA_LZ7), was able to lyse P. aeruginosa both in planktonic cultures and in alginate microbeads (an in vivo-like biofilm model). Additionally, we showed that the phage cocktail administered intranasally or intraperitoneally effectively rescued mice from chronic lung infection with P. aeruginosa. Our work explores the potential use of phages as an alternative therapeutic agent against chronic lung infections caused by P. aeruginosa strains.