Safety and immunogenicity of heterologous boost immunization with an adenovirus type-5-vectored and protein-subunit-based COVID-19 vaccine (Convidecia/ZF2001): a randomized, observer-blinded, placebo-controlled trial

BackgroundHeterologous boost vaccination has been proposed as an option to elicit stronger and broader, or longer-lasting immunity. We assessed the safety and immunogenicity of heterologous immunization with a recombinant adenovirus type-5-vectored COVID-19 vaccine (Convidecia) and a protein-subunit-based COVID-19 vaccine (ZF2001). Methods and FindingsWe did a randomized, observer-blinded, placebo-controlled trial in healthy adults previously received one dose of Convidecia. Participants were randomly assigned (2:1) to receive either ZF2001 (vaccine group) or a trivalent inactivated influenza vaccine (TIV) (placebo group) at either 28-day or 56-day intervals. For both regimens, all participants received the 2nd injection with ZF2001 at 4 months after a dose of ZF2001 or TIV, with three-dose schedules of Convidecia/Convidecia/ZF2001 at day 0, day 28 and month 5 (referred to as CV/ZF/ZF (D0-D28-M5)) and CV/ZF/ZF (D0-D56-M6), and two-dose schedules of CV/ZF (D0-M5) and CV/ZF (D0-M6). The primary outcome was the geometric mean titer (GMT) of the neutralizing antibodies against live SARS-CoV-2 virus 14 days after each boost vaccination. The safety outcome was 7-day reactogenicity, measured as solicited local or systemic adverse reactions after each vaccination. Between April 7, 2021, and May 6, 2021, 120 participants were enrolled, among whom 60 were randomly assigned to receive ZF2001 (n=40) or TIV (n=20) at a 28-day interval, and 60 were randomly assigned to receive ZF2001 (n=40) or TIV (n=20) at a 56-day interval. 113 (94.2%) participants received the 2nd injection with ZF2001 4 months after a dose of ZF2001 or TIV. A total of 26 participants (21.7%) reported solicited adverse events within 7 days post boost vaccinations, and all the reported adverse reactions were mild. Among participants receiving ZF001 as second dose, the GMTs of neutralizing antibodies increased to 58.4 IU/ml (42.8-79.8) in 0-28 regimen, and to 80.8 IU/ml (53.1-122.9) in 0-56 regimen at 14 days post first boost dose. The GMTs of neutralizing antibodies increased to 334.9 IU/ml (95% CI 230.4, 486.9) in C/Z/Z (D0-D28-M5) regimen, and 441.2 IU/ml (260.8, 746.4) in C/Z/Z (D0-D56-M6) regimen at 14 days after the third dose. Two-dose schedules of CV/ZF (D0-M5) and CV/ZF (D0-M6) induced comparable antibody level comparable with that elicited by three-dose schedules, with the GMTs of 282.9 IU/ml (142.5, 561.8) and 293.9 IU/ml (137.6, 627.9), respectively. Study limitations include the absence of vaccine effectiveness in real-world, and current lack of immune persistence data and the neutralizing antibodies to Omicron. ConclusionsHeterologous boosting with ZF001 following primary vaccination of Convidecia is safe and more immunogenic than a single dose of Convidecia. These results support flexibility in cooperating viral vectored vaccines and recombinant protein vaccine. Trial RegistrationClinicalTrial.gov NCT04833101

Human Identical Sequences of SARS-CoV-2 Promote Clinical Progression of COVID-19 by Upregulating Hyaluronan via NamiRNA-Enhancer Network

The COVID-19 pandemic is a widespread and deadly public health crisis. The pathogen SARS-CoV-2 replicates in the lower respiratory tract and causes fatal pneumonia. Although tremendous efforts have been put into investigating the pathogeny of SARS-CoV-2, the underlying mechanism of how SARS-CoV-2 interacts with its host is largely unexplored. Here, by comparing the genomic sequences of SARS-CoV-2 and human, we identified five fully conserved elements in SARS-CoV-2 genome, which were termed as "human identical sequences (HIS)". HIS are also recognized in both SARS-CoV and MERS-CoV genome. Meanwhile, HIS-SARS-CoV-2 are highly conserved in the primate. Mechanically, HIS-SARS-CoV-2, behaving as virus-derived miRNAs, directly target to the human genomic loci and further interact with host enhancers to activate the expression of adjacent and distant genes, including cytokines gene and angiotensin converting enzyme II (ACE2), a well-known cell entry receptor of SARS-CoV-2, and hyaluronan synthase 2 (HAS2), which further increases hyaluronan formation. Noteworthily, hyaluronan level in plasma of COVID-19 patients is tightly correlated with severity and high risk for acute respiratory distress syndrome (ARDS) and may act as a predictor for the progression of COVID-19. HIS antagomirs, which downregulate hyaluronan level effectively, and 4-Methylumbelliferone (MU), an inhibitor of hyaluronan synthesis, are potential drugs to relieve the ARDS related ground-glass pattern in lung for COVID-19 treatment. Our results revealed that unprecedented HIS elements of SARS-CoV-2 contribute to the cytokine storm and ARDS in COVID-19 patients. Thus, blocking HIS-involved activating processes or hyaluronan synthesis directly by 4-MU may be effective strategies to alleviate COVID-19 progression.

MR T2WI demonstration of sciatic nerve injury in rabbits / 中国医学影像技术

Objective To investigate the relationship between MRI signal,pathological changes and neurological function after sciatic nerve injury in rabbits.Methods Twenty New Zealand white rabbits were randomly and evenly divided into 5 groups,and the right sciatic nerve crush models were established.T2 fat suppression fast recovery spin echo (T2 fs FRFSE) sequence scanning was performed 3 days,7 days,2 weeks,3 weeks and 4 weeks after injury,and TE was set as 30,60 and 90 ms,respectively.Signal intensity ratio (SIR) and relative signal intensity (△S) of proximal and distal part of injured nerve and control side nerve were measured.The relationship between SIR,△S,pathology and rabbit lower limb nerve function were analyzed.Results In the distal part of injured nerve,SIR and △S increased 3-7 days after injury,pathological results showed vacuolar degeneration,and basic toe function lost was found.SIR and △S reached the peak 2 weeks after injury,with most serious disintegration of myelin and toe function disable.SIR,△S and toe function disable gradually recovered,and the nerve regenerated at 3-4 weeks after injury.The injure display rate of T2 fs FRFSE images with TE=90 and 60 ms,SIR of both distal and proximal part of injured nerve were higher than those on images with TE=30 ms (all P＜0.05).Conclusion SIR and △S changes on T2 fs FRFSE imaging can be used to predict rabbit nerve injury.

Research on the relationship among nurses′ perceptions of patient safety culture, nursing practice ;environment and the report barrier of nursing adverse events / 中国实用护理杂志

Objective To explore the relationship among nurses′perceptions of patient safety culture, nursing practice environment and the report barrier of nursing adverse event. Methods Totally 513 registered nurses from six hospitals in Zhengzhou were investigated with Patient Safety Culture Assessing Scale, Work Environment Questionnaire and Report Barriers Questionnaire. Results The mean scores of nurses′perceptions of patient safety culture, nursing practice environment and report barriers of nursing adverse events were (3.85±0.55), (3.84±0.53) and (2.47±0.55). The nurses′perceptions of patient safety culture were positively correlated to nursing practice environment (r=0.393,P<0.01), negatively correlated to report barriers of nursing adverse events (r=-0.372,P<0.01). The influencing factors of nurses′perceptions of patient safety culture were colleague relationship, punitive culture, allocation of medical resources, marital status, quality control, significance of report, gender and education, which could explain 33.8 percent for the variances. Conclusions The level of nurses′perceptions of patient safety culture is higher than the average level. The nursing managers should build supportive nursing practice environment and the non-punitive reporting system of nursing adverse events. Cultivate the beliefs and attitudes of nursing safety and focus on the impact of occupational stress to patient safety in order to enhance safety nursing.

The research about relationships among the balance between nurse's work and family, the nursing practice environment and demission intention / 中国实用护理杂志

Objective To determine the relationships among the balance between nurse's work and family,the nursing practice environment and demission intention.Methods A total of 351 nurses were recruited from 5 hospitals in Zhengzhou by convenience sampling method.They were investigated using the Questionnaires for balance between nurse's work and family,the nursing practice environment and demission intention.Results The mean scores of the balance between nurse's work and family,the nursing practice environment and demission intention was (3.09±0.46),(2.86±0.48),(2.51 ±0.57).The predictors of demission intention of nurses were rational allocation of resources,age,work disturbs family,and family promotes work.Conclusions The levels of the balance between nurse's work and family,the nursing practice environment and demission intention are all in the medium.The balance between nurse's work and family and the nursing practice environment have direct positive influence on demission intention.