Objective To construct a recombinant poxvirus vector vaccine, rVTTδTK-RBD, and to evaluate its safety and immunogenicity. Methods The receptor-binding domain (RBD) gene was synthesized with reference to the gene sequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was inserted into the polyclonal site of the self-constructed recombinant plasmid pSTKE, to construct the recombinant poxvirus shuttle vector pSTKE-RBD. This was then transfected into BHK-21 cells pre-infected with the vaccinia virus Tiantan strain (VTT). The recombinant poxvirus rVTTδTK-RBD was successfully obtained after several rounds of fluorescence phage screening. The effect of rVTTδTK-RBD on the body mass of BALB/c mice was detected after immunizing mice by intra-nasal vaccination. The levels of specific and neutralizing antibodies produced by rVTTδTK-RBD on BALB/c mice were analyzed after immunizing mice intramuscularly. The effect of rVTTδTK-RBD on T cell subsets in BALB/c mice was detected by flow cytometry. Results Through homologous recombination, enhanced green fluorescent protein (EGFP) screening marker, and multiple rounds of fluorescent phosphorescence phage screening, a recombinant poxvirus rVTTδTK-RBD, expressing RBD with deletions in the thymidine kinase (TK) gene, was successfully obtained, which was validated by PCR. The in vivo experiments on BALB/c mice showed that rVTTδTK-RBD was highly immunogenic against SARS-CoV-2 and significantly reduced toxicity to the body compared to the parental strain VTT. Conclusion The recombinant poxvirus vaccine rVTTδTK-RBD against SARS-CoV-2 is successfully constructed and obtained, with its safety and immunogenicity confirmed through various experiments.
Animals ; Mice ; SARS-CoV-2/genetics* ; COVID-19 ; Vaccines, Synthetic/genetics* ; Genes, Reporter ; Bacteriophages ; Mice, Inbred BALB C

Objective To investigate the trends in the disease burden of schistosomiasis worldwide and in China, and Zimbabwe from 1990 to 2019, so as to provide insights into the formulation of the schistosomiasis control strategy in Zimbabwe. Methods Based on Global Burden of Disease Study 2019 (GBD 2019) data sources, the age-standardized prevalence, mortality, disability-adjusted life year (DALY) rate of schistosomiasis were compared in the world, China, and Zimbabwe and the trends in the disease burden of schistosomiasis from 1990 to 2019 were investigated using Joinpoint regression analysis. In addition, the associations between the burden of schistosomiasis worldwide and in China and Zimbabwe from 1990 to 2019 and socio-demographic index (SDI) were examined using Pearson correlation analysis. Results The age-standardized prevalence, mortality, and DALY rate of schistosomiasis were 1 804.95/10⁵, 0.14/10⁵ and 20.92/10⁵ in the world, 707.09/10⁵, 0.02/10⁵ and 5.06/10⁵ in China, and 2 218.90/10⁵, 2.39/10⁵ and 90.09/10⁵ in Zimbabwe in 2019, respectively. The global prevalence, mortality, and DALY rate of schistosomiasis appeared a tendency towards a rise followed by a decline with age in 2019, while the prevalence and DALY rate of schistosomiasis appeared a tendency towards a sharp rise followed by a fluctuating decline in both China and Zimbabwe, and the mortality of schistosomiasis appeared a tendency towards a rise. The age-standardized prevalence [average annual percent change (AAPC) = −1.31%, −2.22% and −6.12%; t = −20.07, −83.38 and −53.06; all P values < 0.05)] and DALY rate of schistosomiasis (AAPC = −1.91%,−4.17% and −2.08%; t = −31.89, −138.70 and −16.45; all P values < 0.05) appeared a tendency towards a decline in the world, China and Zimbabwe from 1990 to 2019, and the age-standardized mortality of schistosomiasis appeared a tendency towards a decline in the world and China (AAPC = −3.46% and −8.10%, t = −41.03 and −61.74; both P values < 0.05), and towards a rise followed by a decline in Zimbabwe (AAPC = 1.35%, t = 4.88, P < 0.05). In addition, Pearson correlation analysis showed that the age-standardized prevalence (r = −0.75, P < 0.05), mortality (r = −0.73, P < 0.05), and DALY rate of schistosomiasis (r = −0.77, P < 0.05) correlated negatively with SDI in the world, China and Zimbabwe from 1990 to 2019. Conclusions The disease burden of schistosomiasis appeared a remarkable decline in China from 1990 to 2019, and the prevalence of schistosomiasis showed a tendency towards a decline in Zimbabwe from 1990 to 2019; however, the mortality and DALY rate of schistosomiasis in Zimbabwe topped in the world. A schistosomiasis control strategy with adaptations to local epidemiology and control needs of schistosomiasis is needed to facilitate the elimination of schistosomiasis in Zimbabwe.

Background: Tigecycline, eravacycline, and omadacycline are recently developed tetracyclines. Susceptibility of microbes to these tetracyclines and their molecular mechanisms have not been well elucidated. We investigated the susceptibility of Moraxella catarrhalis to tigecycline, eravacycline, and omadacycline and its resistance mechanisms against these tetracyclines. Methods: A total of 207 non-duplicate M. catarrhalis isolates were collected from different inpatients. The minimum inhibitory concentrations (MICs) of the tetracyclines were determined by broth microdilution. Tigecycline-, eravacycline-, or omadacycline-resistant isolates were induced under In Vitro pressure. The tet genes and mutations in the 16S rRNA was detected by PCR and sequencing. Results: Eravacycline had a lower MIC50 (0.06 mg/L) than tigecycline (0.125 mg/L) or omadacycline (0.125 mg/L) against M. catarrhalis isolates. We found that 136 isolates (65.7%) had the tetB gene, and 15 (7.2%) isolates were positive for tetL; however, their presence was not correlated with high tigecycline, eravacycline, or omadacycline ( ≥ 1 mg/L) MICs.Compared with the initial MIC after 160 days of induction, the MICs of tigecycline or eravacycline against three M. catarrhalis isolates increased ≥ eight-fold, while those of omadacycline against two M. catarrhalis isolates increased 64-fold. Mutations in the 16S rRNA genes (C1036T and/or G460A) were observed in omadacycline-induced resistant isolates, and increased RR (the genes encoding 16SrRNA (four copies, RR1-RR4) copy number of 16S rRNA genes with mutations was associated with increased resistance to omadacycline. Conclusions Tigecycline, eravacycline, and omadacycline exhibited robust antimicrobial effects against M. catarrhalis. Mutations in the 16S rRNA genes contributed to omadacycline resistance in M. catarrhalis.

Objective To explore the possible safety difference of anti-infective agents with the same generic drug name produced by different manufacturers. Methods Spontaneous Reporting System for Adverse Drug Reactions of Beijing was searched. The reports of adverse drug reactions(ADR)of levofloxacin,azithromycin,moxifloxacin,clindamycin,cefuroxime,etimicin,cefoperazone sulbactam sodium,cefoxitin,ceftriaxone and ornidazole from January 2009 to December 2013 were collected. The number of ADR reports,types of ADR,suspicious drugs which induced ADR,and the manufacturers were recorded. The number of ADR signals was detected by reporting odds ratio(ROR)method. The safety of drugs was evaluated according to the number of signal and the type of ADR. Results A total of 18 366 ADR reports of 10 kinds of anti-infective drugs were collected. The top five ADR′s types were skin and subcutaneous tissue diseases(7 644),gastrointestinal diseases(2 505),systemic diseases and various parts of the site of treatment(1 761),nervous system disease(1 592)and immune system diseases (1 254)successively. The sum of the digits above accounted for 80.3% in total number of 10 kinds of anti-infective drugs ADR reports(14 756/18 366). The drugs which caused the five kinds of ADR were levofloxacin,azithromycin and clindamycin/moxifloxacin mainly. The numbers of ADR signals of evofloxacin,azithromycin,moxifloxacin,clindamycin,cefuroxime,etimicin,cefoperazone sulbactam sodium,cefoxitin,ceftriaxone,and ornidazole which were detected by ROR method were 17,20,1,23,9, 9,20,5,1 and 9,respectively. The ADR types related to ADR signals were 11,12,1,12,6,8,10,5 and 8,respectively. The numbers of manufacturers related to ADR signals were 9,13,1,14,6,9,11,5, 1 and 9,respectively. Conclusions There are some differences in ADR signals and ADR types among the 10 kinds of anti-infective agents with the same generic drug name produced by different manufacturers. It is suggested that there are some differences in safety of the above-mentioned drugs.

Objective To explore the possible safety difference of anti-infective agents with the same generic drug name produced by different manufacturers. Methods Spontaneous Reporting System for Adverse Drug Reactions of Beijing was searched. The reports of adverse drug reactions(ADR)of levofloxacin,azithromycin,moxifloxacin,clindamycin,cefuroxime,etimicin,cefoperazone sulbactam sodium,cefoxitin,ceftriaxone and ornidazole from January 2009 to December 2013 were collected. The number of ADR reports,types of ADR,suspicious drugs which induced ADR,and the manufacturers were recorded. The number of ADR signals was detected by reporting odds ratio(ROR)method. The safety of drugs was evaluated according to the number of signal and the type of ADR. Results A total of 18 366 ADR reports of 10 kinds of anti-infective drugs were collected. The top five ADR′s types were skin and subcutaneous tissue diseases(7 644),gastrointestinal diseases(2 505),systemic diseases and various parts of the site of treatment(1 761),nervous system disease(1 592)and immune system diseases (1 254)successively. The sum of the digits above accounted for 80.3% in total number of 10 kinds of anti-infective drugs ADR reports(14 756/18 366). The drugs which caused the five kinds of ADR were levofloxacin,azithromycin and clindamycin/moxifloxacin mainly. The numbers of ADR signals of evofloxacin,azithromycin,moxifloxacin,clindamycin,cefuroxime,etimicin,cefoperazone sulbactam sodium,cefoxitin,ceftriaxone,and ornidazole which were detected by ROR method were 17,20,1,23,9, 9,20,5,1 and 9,respectively. The ADR types related to ADR signals were 11,12,1,12,6,8,10,5 and 8,respectively. The numbers of manufacturers related to ADR signals were 9,13,1,14,6,9,11,5, 1 and 9,respectively. Conclusions There are some differences in ADR signals and ADR types among the 10 kinds of anti-infective agents with the same generic drug name produced by different manufacturers. It is suggested that there are some differences in safety of the above-mentioned drugs.

Objectives:To evaluate essential medicines accessibility from the availability, drug price level and affordability perspective in Beijing. Methods:Data was collected from a sample of a Beijing social security database on diabetes in 2013 and a field research on 4 primary healthcare institutions. The essential medicine equipping rate, medium price ratio ( MPR) and poverty-inducing effect were selected as accessibility indicators. Results:Among 21 sample drugs, the nitrendipine, magnesium sulfate, sodium nitroprusside, prazosin, phentolamine and glyburide e-quipping rates are less than 15%. The 9 sample drugs MPR varied from 1. 3 to 27. 4. The hypertension, hyper-lipemia and diabete poverty-inducing rate varied from 0. 44% to 0. 70% in urban areas, and varied from 1. 17% to 1. 88% in rural areas. Conclusion:Some essential medicines in Beijing are equipped with a very low rate, but have a high price level, and the poverty-inducing population is large. We recommend strengthening the monitoring of es-sential medicines accessibility and introducing appropriate supporting policies.