Immunogenicity and safety of an inactivated enterovirus 71 vaccine coadministered with trivalent split-virion inactivated influenza vaccine: A phase 4, multicenter, randomized, controlled trial in China.

Background: Few data exist on the immunogenicity and safety of an inactivated enterovirus 71 vaccine (EV71 vaccine) coadministered with trivalent split-virion inactivated influenza vaccine (IIV3) in infants. Methods: This trial was a phase 4, randomized, controlled trial. Infants aged 6-11 months were eligible, with no history of hand, foot and mouth disease (HFMD) and no history of EV71 vaccine or any influenza vaccine. Eligible infants were randomly assigned to EV71+IIV3 group, EV71 group or IIV3 group. Blood samples were collected on day 0 and 56. Results: Between September 2019 and June 2020, 1151 infants met eligibility criteria and 1134 infants were enrolled. 1045 infants were included in the per-protocol population, including 347 in the EV71+IIV3 group, 343 in the EV71 group, and 355 in the IIV3 group. The seroconversion rate (98.56% vs 98.54%; seroconversion rates difference of 0.02% [95% CI: 0.70-0.98]) and GMT (419.05 vs 503.72; GMT ratio of 0.83 [95% CI 0.70 - 0.98]) of EV71 neutralizing antibodies in the EV71+IIV3 group was not inferior to those in the EV71 group. The non-inferiority results for influenza virus antibodies (A/H1N1, A/H3N2 and B) showed that the seroconversion rates and GMTs of the EV71+IIV3 group were non-inferiority to those of the IIV3 group. Systemic and local adverse event rates were similar between groups. None of serious adverse events (SAEs) were related to vaccination. Conclusions: Coadministration of the EV71 vaccine with IIV3 was safe and did not interfere with immunogenicity. These findings support a viable immunization strategy for infants with the EV71 vaccine coadministered with IIV3 in China. This trial is registered with ClinicalTrials.gov, number NCT04091880.

Exosomal long noncoding RNA lnc-GNAQ-6:1 may serve as a diagnostic marker for gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most aggressive cancers, with limited early diagnostic measures. Tumor-originated exosomal molecules are regarded as suitable candidates for non-invasive diagnosis. This study aimed to investigate the capacity of exosomal long noncoding RNA lnc-GNAQ-6:1 as a biomarker for early diagnosis of GC. METHODS: In this study, we collected sera from 43 patients with gastric cancer and 27 healthy subjects, then exosomes were isolated using commercial kits. Particle size analysis, Western bloting and protein-based exosomes quantification were conducted to identify the isolated exosomes and to evaluate its yield and purity. Expression levels of exosomal lnc-GNAQ-6:1 were detected by quantitative reverse transcription PCR (qRT-PCR). The serum concentrations of traditional biomarker (CA72-4, CEA, and CA19-9) were measured via a chemiluminescent detection system.The receiver operating characteristic curve (ROC) and area under curve (AUC) were used to estimate the diagnostic capacity. Furthermore, we analyzed the potential relationship between serum exosomal lnc-GNAQ-6:1 expression and clinicopathological parameters of gastric cancer. RESULTS: The exosomes extracted in this study exhibited the typical exosome characteristics and purity. Patients with gastric cancer had the higher exosome yield than healthy volunteer. The results of qRT-PCR showed that compared with the healthy control, the expression of lnc-GNAQ-6:1 was significantly lower in the gastric cancer group. The area under the ROC curve is 0.732, which was higher than the diagnostic accuracy of CEA, CA 19-9 and CA72-4. However, the expression level of lnc-GNAQ-6:1 was not correlated with gender, age, tumor metastasis, serum carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 72-4(CA72-4). CONCLUSIONS: Our data demonstrated that serum exosomal lnc-GNAQ-6:1 is lowly expressed in patient with gastric cancer and might be evaluated in larger studies as a new diagnostic marker for gastric cancer.

Serum inflammatory cytokine levels correlate with hand-foot-mouth disease severity: a nested serial case-control study.

BACKGROUND: Hand-food-mouth disease (HFMD) cases can be fatal. These cases develop rapidly, and it is important to predict the severity of HFMD from mild to fatal and to identify risk factors for mild HFMD. The objective of this study was to correlate the levels of serum inflammatory cytokines with HFMD severity. METHODS: This study was designed as a nested serial case-control study. The data collected included general information, clinical symptoms and signs, laboratory findings and serum cytokine levels. RESULTS: The levels of IL-4, IL-6, IL-10, TNF-α and IFN-γ in patients with severe HFMD were significantly higher than in mild patients during the 2nd to 5th day after disease onset. The levels of IL-4, IL-6, IL-10 and IFN-γ increased from the 2nd day to the 4th day and later decreased. The levels of TNF-α were high on the first two days and subsequently decreased. The changes of IL-10, TNF-α and IFN-γ in the controls were similar for all cases. The levels of IL-4, IL-6 and IL-17 in the controls were not significantly different with the progression of HFMD. CONCLUSIONS: Our findings indicate that the IL-4, IL-6, IL-10, TNF-α and IFN-γ levels correlate with HFMD severity.