Exosomes are nano-sized biovesicles released into surrounding body fluids upon fusion of multivesicular bodies and the plasma membrane. They were shown to carry cell-specific cargos of proteins, lipids, and genetic materials, and can be selectively taken up by neighboring or distant cells far from their release, reprogramming the recipient cells upon their bioactive compounds. Therefore, the regulated formation of exosomes, specific makeup of their cargo, cell-targeting specificity are of immense biological interest considering extremely high potential of exosomes as non-invasive diagnostic biomarkers, as well as therapeutic nanocarriers. In present review, we outline and discuss recent progress in the elucidation of the regulatory mechanisms of exosome biogenesis, the molecular composition of exosomes, and technologies used in exosome research. Furthermore, we focus on the potential use of exosomes as valuable diagnostic and prognostic biomarkers for their cell-lineage and state-specific contents, and possibilities as therapeutic vehicles for drug and gene delivery. Exosome research is now in its infancy, in-depth understanding of subcellular components and mechanisms involved in exosome formation and specific cell-targeting will bring light on their physiological activities.

Neonatal invasive disease caused by group B Streptococcus (GBS) represents a significant public health care concern globally. However, data related to disease burden, serotype distribution and molecular epidemiology in China and other Asian countries are very few and specifically relative to confined regions. The aim of this study was to investigate the genetic characteristics of GBS isolates recovered from neonates with invasive disease during 2013-2014 at Guangzhou and Changsha hospitals in southern mainland China. We assessed the capsular polysaccharide (CPS) type, pilus islands (PIs) distribution and hvgA gene presence in a panel of 26 neonatal clinical isolates, of which 8 were recovered from Early Onset Disease (EOD) and 18 from Late Onset Disease (LOD). Among 26 isolates examined, five serotypes were identified. Type III was the most represented (15 cases), particularly among LOD strains (n=11), followed by types Ib (n=5), V (n=3), Ia (n=2) and II (n=1). We performed whole-genome sequencing (WGS) analysis and antimicrobial susceptibility testing on the 14 serotype III isolates belonging to the hypervirulent Clonal Complex 17 (serotype III-CC17).The presence of PI-2b alone was associated with 13 out of 14 serotype III-CC17 strains. Genome analysis led us to identify two multi-drug resistance gene clusters harbored in two new versions of integrative and conjugative elements (ICEs), carrying five or eight antibiotic resistance genes, respectively. These ICEs replaced the 16 kb-locus that normally contains the PI-1 operon. All isolates harboring the identified ICEs showed multiple resistances to aminoglycoside, macrolide and tetracycline antibiotic classes. In conclusion, we report the first whole-genome sequence analysis of 14 GBS serotype III-CC17 strains isolated in China, representing the most prevalent lineage causing neonatal invasive disease. The acquisition of newly identified ICEs conferring multiple antibiotic resistances could in part explain the spread of this specific clone among Chinese neonatal isolates and underlines the need for a constant epidemiological surveillance.

Background: Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the presence of anti-mitocondrial autoantibodies (AMA) which has an essential role also for diagnosis. In addition, also some anti-nuclear antibodies (ANA) have been shown to be highly specific PBC. The purpose of this study was to assess the prevalence of PBC among the adults referring hospital for annual health check-up in Southern China by screening sera for PBC-specific autoantibodies.Methods: AMA and ANA were screened in 8,126 adults (mean age 44 ± 15 years, 48% females) by indirect immunofluorenscence (IIF). Positive sera were tested by ELISA/immunoblotting for AMA-M2, anti-sp100 and anti-gp210. A diagnosis of PBC was re-assessed six months after the initial testing.Results: Out of 8,126 individuals 35 were positive for AMA and 79 positive for ANA. Nineteen, 4, and 3 of the subjects positive for AMA and/or ANA showed reactivity for AMA-M2, anti-sp100 or gp210, respectively, further tested with ELISA/immunoblotting. Fourteen in the 39 individuals positive for AMA at IIF, AMA-M2, anti-gp210, or anti-sp100 had abnormal cholestatic liver functional indices. One definite and 3 probable PBC diagnosis could be made in 4 cases including 3 females and 1 male after half a year.Conclusions: We found a point prevalence rate of PBC among Southern Chinese adults attending for yearly health check-up of 492 cases per million (95% CI, 128 to 1,093) and 1,558 cases per million (95% CI, 294 to 3,815) for women over 40, a finding similar to prevalence reported in other geographical areas.

AIM: To validate the value of aspartate aminotransferase to platelet ratio index (APRI) in assessment of liver fibrosis and prediction of postoperative prognosis of biliary atresia (BA) infants from Mainland China. METHODS: Medical records of 153 BA infants who were hospitalized from January 2010 to June 2013 were reviewed. The efficacy of APRI for diagnosis of liver fibrosis was assessed using the receiver operator characteristic (ROC) curve compared to the pathological Metavir fibrosis score of the liver wedge specimens of 91 BA infants. The prognostic value of preoperative APRI for jaundice persistence, liver injury, and occurrence of cholangitis within 6 mo after KP was studied based on the follow-up data of 48 BA infants. RESULTS: APRI was significantly correlated with Metavir scores (r_s = 0.433; P < 0.05). The mean APRI value was 0.76 in no/mild fibrosis group (Metavir score F0-F1), 1.29 in significant fibrosis group (F2-F3), and 2.51 in cirrhosis group (F4) (P < 0.001). The area under the ROC curve (AUC) of APRI for diagnosing significant fibrosis and cirrhosis was 0.75 (P < 0.001) and 0.81 (P = 0.001), respectively. The APRI cut-off of 0.95 was 60.6% sensitive and 76.0% specific for significant fibrosis diagnosis, and a threshold of 1.66 was 70.6% sensitive and 82.7% specific for cirrhosis. The preoperative APRI in infants who maintained jaundice around 6 mo after KP was higher than that in those who did not (1.86 ± 2.13 vs 0.87 ± 0.48, P < 0.05). The AUC of APRI for prediction of postoperative jaundice occurrence was 0.67. A cut-off value of 0.60 showed a sensitivity of 66.7% and a specificity of 83.3% for the prediction of jaundice persistence. Preoperative APRI had no significant association with later liver injury or occurrence of cholangitis. CONCLUSION: Our study demonstrated that APRI could diagnose significant liver fibrosis, especially cirrhosis in BA infants, and the elevated preoperative APRI predicts jaundice persistence after KP.

Background: Neonatal sepsis (NS) is one of the leading causes of infant morbidity and mortality, but little is known about pathogen incidence and distribution in China. Methods: In this retrospective study (January 2012 to December 2016), culture-proven cases aged less than 28 days with diagnosed NS in the Guangzhou Women and Children’s Medical Center, South China, were analyzed for pathogen incidence and antimicrobial resistance. Results: A total of 620 isolates were identified from 597 NS cases. Gram-negative bacteria (n=371, 59.8%) dominated over Gram-positive bacteria (n=218, 35.2%) and fungi (n=30, 4.8%). Klebsiella pneumoniae (21.9%), Escherichia coli (21.9%), group B Streptococcus (GBS, 13.2%), and Staphylococcus aureus (6.8%) were the four most predominant pathogens. In early-onset sepsis (EOS), GBS (30.0%) and E. coli (20.0%) were dominant, whereas in late-onset sepsis (LOS), K. pneumoniae (25.6%) and E. coli (22.4%) were dominant. E. coli (25.2%) and GBS (17.7%) were the most frequently isolated from term patients, whereas K. pneumoniae was the most frequently isolated from preterm patients (34.9%). Of the infected infants, 9.5% died from sepsis, most commonly by E. coli infection (16.2%). Among 91,215 live births (LBs) delivered in the study hospital (2012–2016), 252 infants developed sepsis infection (2.76 per 1000 LBs, 95% CI 2.4–3.1), including EOS (0.78 per 1000 LBs) and LOS (2.13 per 1000 LBs). All GBS isolates were susceptible to β-lactam antibiotics, and S. aureus, including methicillin-resistant isolates, were susceptible to vancomycin. An extended-spectrum β-lactamase producer was identified in 37.3% of E. coli and 50.4% of K. pneumoniae. Conclusion: K. pneumoniae was the most frequent pathogen in culture-proven NS in South China, primarily associated with LOS in preterm, whereas GBS was the dominant pathogen in EOS. E. coli was common in both episodes with the highest mortality.