Simplified acute physiology score III is excellent for predicting in-hospital mortality in coronary care unit patients with acute myocardial infarction: A retrospective study

BackgroundCoronary care unit (CCU) patients with acute myocardial infarction (AMI) lack effective predictors of in-hospital mortality. This study aimed to investigate the performance of four scoring systems in predicting in-hospital mortality in CCU patients with AMI.MethodsThe baseline data, the logistic organ dysfunction system (LODS), the Oxford acute severity of illness score (OASIS), the simplified acute physiology score II (SAPS II), and the simplified acute physiology score III (SAPS III) scores of the patients were extracted from the fourth edition of the Medical Information Mart for Critical Care (MIMIC-IV) database. Independent risk factors for in-hospital mortality were identified by regression analysis. We performed receiver operating characteristic (ROC) curves and compared the area under the curve (AUC) to clarify the predictive value of the four scoring systems. Meanwhile, Kaplan–Meier curves and decision curve analysis (DCA) were performed to determine the optimal scoring system for predicting in-hospital mortality.ResultsA total of 1,098 patients were included. The SAPS III was an independent risk factor for predicting in-hospital mortality in CCU patients with AMI before and after the propensity score matching (PSM) analysis. The discrimination of in-hospital mortality by SAPS III was superior to that of LODS, OASIS, and SAPS II. The AUC of the SAPS III scoring system was the highest among the four scoring systems, at 0.901 (before PSM) and 0.736 (after PSM). Survival analysis showed that significantly more in-hospital mortality occurred in the high-score SAPS III group compared to the low-score SAPS III group before PSM (HR 7.636, P < 0.001) and after PSM (HR 2.077, P = 0.005). The DCA curve of SAPS III had the greatest benefit score across the largest threshold range compared to the other three scoring systems.ConclusionThe SAPS III was an independent risk factor for predicting in-hospital mortality in CCU patients with AMI. The predictive value for in-hospital mortality with SAPS III is superior to that of LODS, OASIS, and SAPS II. The results of the DCA analysis suggest that SAPS III may provide a better clinical benefit for patients. We demonstrated that SAPS III is an excellent scoring system for predicting in-hospital mortality for CCU patients with AMI

Progress in the Development of Universal Influenza Vaccines

Influenza viruses pose a significant threat to human health. They are responsible for a large number of deaths annually and have a serious impact on the global economy. There are numerous influenza virus subtypes, antigenic variations occur continuously, and epidemic trends are difficult to predict—all of which lead to poor outcomes of routine vaccination against targeted strain subtypes. Therefore, the development of universal influenza vaccines still constitutes the ideal strategy for controlling influenza. This article reviews the progress in development of universal vaccines directed against the conserved regions of hemagglutinin (HA), neuraminidase (NA), and other structural proteins of influenza viruses using new technologies and strategies with the goals of enhancing our understanding of universal influenza vaccines and providing a reference for research into the exploitation of natural immunity against influenza viruses

Hemagglutinin Gene Variation Rate of H9N2 Avian Influenza Virus by Vaccine Intervention in China

H9N2 subtype avian influenza virus (AIV) is widespread globally, with China being the main epidemic center. Inactivated virus vaccination was adopted as the main prevention method in China. In this study, 22 hemagglutinin (HA) sequences were obtained from all inactivated vaccine strains of H9N2 subtype AIVs in China since its introduction. A phylogenetic analysis of the vaccine sequences and HA sequences of all published H9N2 subtype AIVs was conducted to investigate the relationship between vaccine use and the virus genetic diversity of the virus. We found that during 2002–2006, when fewer vaccines were used, annual genetic differences between the HA sequences were mainly distributed between 0.025 and 0.075 and were mainly caused by point mutations. From 2009 to 2013, more vaccines were used, and the genetic distance between sequences was about 10 times greater than between 2002 and 2006, especially in 2013. In addition to the accumulation of point mutations, insertion mutations may be the main reason for the large genetic differences between sequences from 2009 to 2013. These findings suggest that the use of inactivated vaccines affected point mutations in the HA sequences and that the contribution of high-frequency replacement vaccine strains to the rate of virus evolution is greater than that of low-frequency replacement vaccine strains. The selection pressure of the vaccine antibody plays a certain role in regulating the variation of HA sequences in H9N2 subtype AIV

Optimization of Two Steps in Scale-Up Synthesis of Nannocystin A

We have accomplished a 10-step (longest linear) total synthesis of nannocystin A on a four hundred milligram scale. The previously reported Kobayashi vinylogous Mukaiyama aldol reaction to connect C4 and C5 was unreproducible during the scaling up process. A more convenient and cost-efficient Keck asymmetric vinylogous aldol reaction was employed to improve this transformation

Role of Osteoprotegerin and Its Gene Polymorphisms in the Occurrence of Left Ventricular Hypertrophy in Essential Hypertensive Patients

Overall view from N. Grand Avenue, looking southwest; Dorothy Chandler Pavilion at left; A 739-seat thrust stage at the Los Angeles Music Center designed by Welton Becket and Associates. The smallest of the three venues, the Taper is flanked by the Dorothy Chandler Pavilion and the Ahmanson Theatre on the Music Center Plaza. Mr. Becket designed the center in the style of New Formalism, which emphasized geometric shapes. The perfectly circular Taper is considered one of his best works, featuring a distinctive decorated drum of a design with its exterior wrapped in a lacy precast relief by Jacques Overhoff. The lobby has a curving, abalone wall by Tony Duquette. Source: Wikipedia; http://en.wikipedia.org/wiki/Main_Page (accessed 7/29/2013

Robust induction of interferon and interferon-stimulated gene expression by influenza B/Yamagata lineage virus infection of A549 cells.

Influenza B virus (IBV) belongs to the Orthomyxoviridae family and generally causes sporadic epidemics but is occasionally deadly to individuals. The current research mainly focuses on clinical and pathological characteristics of IBV. However, to better prevent or treat the disease, one must determine the strategies developed by IBV to invade and disrupt cellular proteins and approach to replicate itself, to suppress antiviral innate immunity, and understand how the host responds to IBV infection. The B/Shanghai/PD114/2018 virus was able to infect alveolar epithelial cells (A549) cells, with good potential for replication. To identify host cellular responses against IBV infection, differentially expressed genes (DEGs) were obtained using RNA sequencing. The GO and KEGG pathway term enrichment analyses with the DEGs were performed, and we found that the DEGs were primary involved in metabolic processes and cellular function, which may be related to the host response, including the innate immune response against the virus. Our transcriptome analysis results demonstrated robust induction of interferon and interferon-stimulated gene expression by IBV in human cells during the early stages of infection, providing a foundation for further studies focused on antiviral drug development and interactions between the virus and host

Evaluation of Cellular Immunity with ASFV Infection by Swine Leukocyte Antigen (SLA)—Peptide Tetramers

African swine fever virus (ASFV) causes acute hemorrhagic fever in domestic pigs and wild boars, resulting in incalculable economic losses to the pig industry. As the mechanism of viral infection is not clear, protective antigens have not been discovered or identified. In this study, we determined that the p30, pp62, p72, and CD2v proteins were all involved in the T cell immune response of live pigs infected with ASFV, among which p72 and pp62 proteins were the strongest. Panoramic scanning was performed on T cell epitopes of the p72 protein, and three high-frequency positive epitopes were selected to construct a swine leukocyte antigen (SLA)-tetramer, and ASFV-specific T cells were detected. Subsequently, the specific T cell and humoral immune responses of ASFV-infected pigs and surviving pigs were compared. The results demonstrate that the specific T cellular immunity responses gradually increased during the infection and were higher than that in the surviving pigs in the late stages of infection. The same trend was observed in specific humoral immune responses, which were highest in surviving pigs. In general, our study provides key information for the exploration of ASFV-specific immune responses and the development of an ASFV vaccine

Identification of an Arylnaphthalene Lignan Derivative as an Inhibitor against Dengue Virus Serotypes 1 to 4 (DENV-1 to -4) Using a Newly Developed DENV-3 Infectious Clone and Replicon

ABSTRACT Dengue virus (DENV) is the most widespread arbovirus, causing symptoms ranging from dengue fever to severe dengue, including hemorrhagic fever and shock syndrome. Four serotypes of DENV (DENV-1 to -4) can infect humans; however, no anti-DENV drug is available. To facilitate the study of antivirals and viral pathogenesis, here we developed an infectious clone and a subgenomic replicon of DENV-3 strains for anti-DENV drug discovery by screening a synthetic compound library. The viral cDNA was amplified from a serum sample from a DENV-3-infected individual during the 2019 epidemic; however, fragments containing the prM-E-partial NS1 region could not be cloned until a DENV-3 consensus sequence with 19 synonymous substitutions was introduced to reduce putative Escherichia coli promoter activity. Transfection of the resulting cDNA clone, plasmid DV3syn, released an infectious virus titer of 2.2 × 102 focus-forming units (FFU)/mL. Through serial passages, four adaptive mutations (4M) were identified, and addition of 4M generated recombinant DV3syn_4M, which produced viral titers ranging from 1.5 × 104 to 6.7 × 104 FFU/mL and remained genetically stable in transformant bacteria. Additionally, we constructed a DENV-3 subgenomic replicon and screened an arylnaphthalene lignan library, from which C169-P1 was identified as exhibiting inhibitory effects on viral replicon. A time-of-drug addition assay revealed that C169-P1 also impeded the internalization process of cell entry. Furthermore, we demonstrated that C169-P1 inhibited the infectivity of DV3syn_4M, as well as DENV-1, DENV-2, and DENV-4, in a dose-dependent manner. This study provides an infectious clone and a replicon for the study of DENV-3 and a candidate compound for future development against DENV-1 to -4 infections. IMPORTANCE Dengue virus (DENV) is the most prevalent mosquito-transmitted virus, and there is no an anti-dengue drug. Reverse genetic systems representative of different serotype viruses are invaluable tools for the study of viral pathogenesis and antiviral drugs. Here, we developed an efficient infectious clone of a clinical DENV-3 genotype III isolate. We successfully overcame the instability of flavivirus genome-length cDNA in transformant bacteria, an unsolved issue for construction of cDNA clones of flaviviruses, and adapted this clone to efficiently produce infectious viruses following plasmid transfection of cell culture. Moreover, we constructed a DENV-3 subgenomic replicon and screened a compound library. An arylnaphthalene lignan, C169-P1, was identified as an inhibitor of virus replication and cell entry. Finally, we demonstrated that C169-P1 exhibited a broad-spectrum antiviral effect against the infections with DENV-1 to -4. The reverse genetic systems and the compound candidate described here facilitate the study of DENV and related RNA viruses