ABSTRACT
The global emergence of SARS-CoV-2 variants has led to increasing breakthrough infections in vaccinated populations, calling for an urgent need to develop more effective and broad-spectrum vaccines to combat COVID-19. Here we report the preclinical development of RQ3013, an mRNA vaccine candidate intended to bring broad protection against SARS-CoV-2 variants of concern (VOCs). RQ3013, which contains pseudouridine-modified mRNAs formulated in lipid nanoparticles, encodes the spike(S) protein harboring a combination of mutations responsible for immune evasion of VOCs. Here we characterized the expressed S immunogen and evaluated the immunogenicity, efficacy, and safety of RQ3013 in various animal models. RQ3013 elicited robust immune responses in mice, hamsters, and nonhuman primates (NHP). It can induce high titers of antibodies with broad cross-neutralizing ability against the Wild-type, B.1.1.7, B.1.351, B.1.617.2, and the omicron B.1.1.529 variants. In mice and NHP, two doses of RQ3013 protected the upper and lower respiratory tract against infection by SARS-CoV-2 and its variants. We also proved the safety of RQ3013 in NHP models. Our results provided key support for the evaluation of RQ3013 in clinical trials.
ABSTRACT
Objective To summarize the minimally invasive transthoracic ventricular septal defect (VSD) occlusion operation experience in the clinical application. Methods 142 VSD patients (admitted from August, 2013 to October, 2014) were chosen. All patients were treated with minimally invasive transthoracic device closure under the monitoring of transoesophageal echocardiogram. Results 136 cases received successful closure, and 6 cases still need CPB conventional extracorporeal circulation operation. After follow-up for 3 ~ 12 months for 102 patients, 16 cases remain residual shunt. Conclusion The short-term therapeutic effect of minimally invasive transthoracic device closure of VSD is satisfying. However , the long-term follow-up remains to be studied.
ABSTRACT
@#: ObjectiveTo compare the clinical significance of motor unit number estimates (MUNE) and conventional electromyogram (EMG) in the evaluation of neuromuscular disorders. MethodsUnder the model of MUNE or quantity of motor unit potential (QMUP), 53 patients with various neurogenic disorders were tested with EMG at extensor digitorum brevis, thenar, or hypothenar eminence. ResultsFor 8 patients with amyotrophic lateralizing sclerosis, large and long-duration polyphasic potentials were detected in needle electrode EMG tests, and the motor unit numbers reduced. For 45 patients with peripheral neuropathies, few distinctive features could not be detected by needle electrode EMG, but motor unit numbers reduced in 2 patients; spontaneous activities were the only abnormality in the other 2 patients, and there were no obviously abnormal changes in the configuration and size of motor unit potentials and in motor unit numbers; EMG tests revealed neurogenic features and motor unit numbers significantly reduced in the remaining 41 patients. ConclusionConventional EMG and MUNE can work for the diagnosis of neuromuscular disorders, and do better in combination.
ABSTRACT
Objective To establish immortalized human hepatocyte lines for studies of bioartificial liver,hepatocyte transplantation,and drug metabolism in vitro.Methods Primary human hepatocytes were isolated by 4-step perfusion technique with collagenase and transfected with recombinant retrovirus containing Simian virus 40 large T antigen(SV40 LT).Subsequently,immortalized human hepatocytes were evaluated by analysis of gene expression and functional characteristics in vitro.Results Two immortalized human hepatocyte lines,HepLi2 and HepLi3,were obtained after primary human hepatocytes being infected by SV40 LT containing recombinant retrovirus for 3-4 weeks.The immortalized human hepatocytes showed classical appearance of hepatocyte observed by phase contrast microscope.The protein expression of SV40 LT in HepLi2 and HepLi3 cells were detected by Western blotting.The mRNA expressions of albumin(Alb),glutathione S-transferase(GST-p),human blood coagulation factor X(HBCF-X)and β-actin in HepLi2 and HepLi3 cells were detected by reverse transcription polymerase chain reaction(RT-PCR),and the mRNA expressions of cytochrome(CY)450 subtypes(CYP3A5,CYP2E1,CYP2C8-19 and CYP3A4)in HepLi2 and HepLi3 cells were also observed by RT-PCR.Levels of alanine transaminase (ALT),lactate dehydrogenase(LDH)and Alb were detected in the supernatant of immortalized human hepatoeyte culture.Conclusions The immortalized human hepatocyte lines have the biological characteristics of primary human hepatocytes and have the CYP450 functions of hepatocytes,which may be heIDful for the studies of bioartificial liver,heoatocvte transplantation and drug metabolism in vitro.
