Background: The effect of probiotic therapy on bacterial vaginosis (BV) is controversial. We conducted a meta-analysis of the efficacy and safety associated with probiotic treatment for BV. Methods: We searched multiple databases covering up to 1 March 2018. Studies published as blinded randomized controlled trials (RCTs), comparing treatment using probiotic versus active or placebo control in BV patients were included, with at least one-month follow-up. Random effects model and trial sequential analysis (TSA) were applied. Results: Ten studies (n = 2321) were included. Compared with placebo, the probiotics-only therapy resulted in a beneficial outcome both in clinical cure rate at the 30th day (risk ratio, RR = 2.57; 95% confidential interval, 95% CI: 1.96 to 3.37), and Nugent score (mean difference, MD = −2.71; 95% CI: −3.41 to −2.00). This effect decreased but remained significant after eight weeks. Probiotics-post-antibiotics therapy had a decreased effect only for a short term and possibly among studies with a mostly black study population. No extra adverse events were observed. The TSA suggested a larger sample size for effective evaluation of the probiotics as a supplementary remedy. Conclusions: Probiotic regimes are safe and may exhibit a short-term and long-term beneficial effect for BV treatment. The ethnic-specific result for the probiotic used after antibiotics is worthy of further study.

Abbreviations: ALT, alanine transaminase; aOR, adjusting odds ratio; APOs, adverse pregnancy outcomes; BMI, body mass index; CI, confidence interval; DAGs, directed acyclic graphs;ELISA, enzyme-linked immunosorbent assay; FDR, false discovery rate; GDM, gestational diabetes mellitus; HBeAg, hepatitis B e antigen; HBsAg, Serum hepatitis B surface antigen; HBV, hepatitis B virus; HDP, hypertensive disorders of pregnancy; ICP, intrahepatic cholestasis pregnancy; LGA, large for gestational age; PROM, premature rupture of the membranes; PW, pregnant women; SGA, small for gestational age; TNF-a, tumour necrosis factor alpha. AbstractIt is not clear whether chronic hepatitis B virus (HBV) infection during pregnancy can increase the risk of adverse pregnancy outcomes for both mothers and neonates. We conducted a hospital-based prospective cohort study on pregnant women (PW) andused an analysis strategy that was guided by directed acyclic graphs (DAGs). Maternal characteristics and major adverse pregnancy outcomes were collected both from questionnaires and hospital-based electronic medical records. Serum hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) status were determined. In total, 3329 of the 3416 pregnant women who received routine antenatal care in a hospital setting at baseline, including 346 HBsAg carriers, were available for analysis.Maternal HBsAg carrier status was associated with an increased risk of intrahepatic cholestasis pregnancy [aOR (adjusting odds ratio) = 1.70; 95% CI (confidence interval) = 1.16-2.49], premature rupture of the membranes (aOR = 1.38; 95% CI = 1.00-1.89) and large for gestational age birth aOR = 1.67; 95% CI = 1.17-2.39).The risk of intrahepatic cholestasis remained in pregnant women with either HBeAgpositive (aOR = 2.96; 95% CI = 1.33-6.62) or HBeAg-negative (aOR = 1.52; 95% CI =1.00-2.32)] status; notably, only maternal HBeAg-negative status was associated with a higher risk of large for gestational age birth (aOR = 1.91; 95% CI = 1.33-2.76).Our results implied that chronic HBV infection during pregnancy may increase the risk of intrahepatic cholestasis of pregnancy, premature rupture of membranes and large for gestational age pregnancies. K E Y W O R D Shepatitis B virus infection, intrahepatic cholestasis during pregnancy, large for gestational age, pregnancy outcomes, premature rupture of the membranes

Avian infectious bronchitis virus (IBV) is a Gammacoronavirus in the family Coronaviridae and causes highly contagious respiratory disease in chickens. Innate immunity plays significant roles in host defense against IBV. Here, we explored the interaction between IBV and the host innate immune system. Severe histopathological lesions were observed in the tracheal mucosa at 3-5 days post inoculation (dpi) and in the kidney at 8 dpi, with heavy viral loads at 1-11 and 1-28 dpi, respectively. The expression of mRNAs encoding Toll-like receptor (TLR) 3 and TLR7 were upregulated at 3-8 dpi, and that of TIR-domain-containing adapter-inducing interferon (IFN) β (TRIF) was upregulated at 21 dpi in the trachea and kidney. Myeloid differentiation primary response protein 88 (MyD88) was upregulated in the trachea during early infection. Tumor necrosis factor receptor-associated factor (TRAF) 3 and TRAF6 were upregulated expression in both tissues. Moreover, melanoma differentiation-associated protein 5 (MDA5), laboratory of genetics and physiology 2 (LGP2), stimulator of IFN genes (STING), and mitochondrial antiviral signaling protein (MAVS), as well as TANK binding kinase 1 (TBK1), inhibitor of kappaB kinase (IKK) ε, IKKα, IKKβ, IFN regulatory factor (IRF) 7, nuclear factor of kappaB (NF-ĸB), IFN-α, IFN-β, various interleukins(ILs), and macrophage inflammatory protein-1β (MIP-1β) were significantly upregulated in the trachea and downregulated in the kidney. These results suggested that the TLR and MDA5 signaling pathways and innate immune cytokine were induced after IBV infection. Additionally, consistent responses to IBV infection were observed during early infection, with differential and complicated responses in the kidney.

The high mutation rates of infectious bronchitis virus (IBV) pose economic threats to the poultry industry. In order to track the genetic evolutionary of IBV isolates circulating in yellow chickens, we continued to conduct the genetic analyses of the structural genes S1, E, M, and N from 64 IBV isolates in southern China during 2009–2017. The results showed that the dominant genotypes based on the four genes had changed when compared with those during 1985–2008. Based on the S1 gene phylogenetic tree, LX4-type (GI-19) was the most dominant genotype, which was different from that during 1985–2008. The second most dominant genotype was LDT3-A-type, but this genotype disappeared after 2012. New-type 1 (GVI-1) isolates showed increasing tendency and there were four aa (QKEP) located in the hypervariable region (HVR) III and one aa (S) insertion in all the New-type 1 isolates. Both the analyses of amino acid entropy and molecular evolutionary rate revealed that the variations from large to small were S1, E, M, and N. Purifying selection was detected in the S1, E, M, and N gene proteins, which was different from the positive selection during 1985–2008. Six isolates were confirmed to be recombinants, possibly generated from a vaccine virus of the 4/91-type or LDT3-A-type and a circulating virus. The estimated times for the most recent common ancestors based on the S1, E, M, and N genes were the years of 1744, 1893, 1940, and 1945, respectively. Bayesian skyline analysis revealed a sharp decrease in genetic diversity of all the four structural genes after 2010 and since late 2015, the viral population rapidly rose. In conclusion, the IBVs circulating in southern China over the past decade have experienced a remarkable change in genetic diversity, dominant genotypes, and selection pressure, indicating the importance of permanent monitoring of circulating strains and the urgency for developing new vaccines to counteract the emerging LX4-type and New-type IBVs.