Case Report: Transformation of natural killer-cell large granular lymphocytic leukemia to aggressive natural killer cell leukemia

Large Granular Lymphocytic Leukemia (LGLL) is a rare clonal proliferative disorder of cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, characterized by persistent expansion of large granular lymphocytes (LGLs) in peripheral blood for over six months. According to the 2022 World Health Organization (WHO) classification, LGLL is categorized into T-LGLL, NK-large granular lymphocytic leukemia (NK-LGLL). Aggressive natural killer cell leukemia (ANKL), as a Mature T-cell and NK-cell leukemia independent of LGLL, also has morphologic characteristics of large granular lymphocytes. This report describes a rare case of NK-LGLL transforming into ANKL. This case highlights the necessity of differential diagnosis in LGLL and suggests that proteasome inhibitors combined with immune checkpoint inhibitors may represent a promising therapeutic strategy for ANKL

Control of sunroof buffeting noise by optimizing the flow field characteristics of a commercial vehicle

When a commercial vehicle is driving with the sunroof open, it is easy for the problem of sunroof buffeting noise to occur. This paper establishes the basis for the design of a commercial vehicle model that solves the problem of sunroof buffeting noise, which is based on computational fluid dynamics (CFD) numerical simulation technology. The large eddy simulation (LES) method was used to analyze the characteristics of the buffeting noise with different speed conditions while the sunroof was open. The simulation results showed that the small vortex generated in the cab forehead merges into a large vortex during the backward movement, and the turbulent vortex causes a resonance response in the cab cavity as the turbulent vortex moves above the sunroof and falls into the cab. Improving the flow field characteristics above the cab can reduce the sunroof buffeting noise. Focusing on the buffeting noise of commercial vehicles, it is proposed that the existing accessories, including sun visors and roof domes, are optimized to deal with the problem of sunroof buffeting noise. The sound pressure level of the sunroof buffeting noise was reduced by 6.7 dB after optimization. At the same time, the local pressure drag of the commercial vehicle was reduced, and the wind resistance coefficient was reduced by 1.55% compared to the original commercial vehicle. These results can be considered as relevant, with high potential applicability, within this field of researchThis work was supported by the National Natural Science Foundation of China (No. 52065013), the Guangxi Youth Science Fund Project (2018GXNSFBA281012), the Innovation-Driven Development Special Fund Project of Guangxi (Guike AA19182004), and the Liuzhou Scientific Research and Planning Development Project (2018AA20301)S

Urine microRNAs as biomarkers for bladder cancer: a diagnostic meta-analysis

BACKGROUND: The diagnostic value of microRNA (miRNA) detection in patients with bladder cancer (BCa) is controversial. We performed a diagnostic meta-analysis to evaluate current evidence on the use of miRNA assays to diagnose BCa. METHODS: We systematically searched PubMed, Embase, and Web of Science for studies published before March 31, 2015. The pooled sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and area under the curve (AUC) were calculated to evaluate the overall test performance. Subgroup analyses were used to explore the between-study heterogeneity. Deeks’ funnel plot asymmetry test was used to test publication bias. We applied the software of RevMan 5.2 and Stata 11.0 to the meta-analysis. RESULTS: A total of 23 studies from nine articles were included in the meta-analysis, with a total of 719 patients and 494 controls. The pooled sensitivity and specificity were 0.75 (95% confidence interval [CI], 0.68–0.80) and 0.75 (95% CI, 0.70–0.80), respectively. The pooled positive likelihood ratio was 3.03 (95% CI, 2.50–3.67); negative likelihood ratio was 0.33 (95% CI, 0.27–0.42); and diagnostic odds ratio was 9.07 (95% CI, 6.35–12.95). The pooled AUC was 0.81 (95% CI, 0.78–0.85). Subgroup analyses indicated that the multiple miRNAs assays and urine supernatant assays showed high accuracies in diagnosing BCa. CONCLUSION: The miRNA assays may serve as potential noninvasive diagnostic tool for the detection of BCa. However, the clinical application of miRNA assays for BCa diagnosis still needs further validation by large prospective studies

Phylogenetic analysis of porcine parvoviruses from swine samples in China

<p>Abstract</p> <p>Background</p> <p>Porcine parvovirus (PPV) usually causes reproductive failure in sows. The objective of the present study was to analyze the phylogenetic distribution and perform molecular characterization of PPVs isolated in China, as well as to identify two field strains, LZ and JY. The data used in this study contained the available sequences for NS1 and VP2 from GenBank, as well as the two aforementioned Chinese strains.</p> <p>Results</p> <p>Phylogenetic analysis shows that the PPV sequences are divided into four groups. The early Chinese PPV isolates are Group I viruses, and nearly all of the later Chinese PPV isolates are Group II viruses. LZ belongs to group II, whereas the JY strain is a Group III virus. This is the first report on the isolation of a Group III virus in China. The detection of selective pressures on the PPV genome shows that the NS1 and VP2 genes are under purifying selection and positive selection, respectively. Moreover, the amino acids in the VP2 capsid are highly variable because of the positive selection.</p> <p>Conclusions</p> <p>Our study provides new molecular data on PPV strains in China, and emphasizes the importance of etiological studies of PPV in pigs.</p

A VLP-Based Vaccine Displaying HBHA and MTP Antigens of Mycobacterium tuberculosis Induces Protective Immune Responses in M. tuberculosis H37Ra Infected Mice

Heparin-binding hemagglutinin (HBHA) and M. tuberculosis pili (MTP) are important antigens on the surface of Mycobacterium tuberculosis. To display these antigens effectively, the fusion protein HBHA-MTP with a molecular weight of 20 kD (L20) was inserted into the receptor-binding hemagglutinin (HA) fragment of influenza virus and was expressed along with matrix protein M1 in Sf9 insect cells to generate influenza virus-like particles (LV20 in short). The results showed that the insertion of L20 into the envelope of the influenza virus did not affect the self-assembly and morphology of LV20 VLPs. The expression of L20 was successfully verified by transmission electron microscopy. Importantly, it did not interfere with the immunogenicity reactivity of LV20 VLPs. We demonstrated that LV20 combined with the adjuvant composed of DDA and Poly I: C (DP) elicited significantly higher antigen-specific antibodies and CD4+/CD8+ T cell responses than PBS and BCG vaccination in mice. It suggests that the insect cell expression system is an excellent protein production system, and LV20 VLPs could be a novel tuberculosis vaccine candidate for further evaluation

Polymorphic genetic characterization of the ORF7 gene of porcine reproductive and respiratory syndrome virus (PRRSV) in China

<p>Abstract</p> <p>Background</p> <p>Porcine reproductive and respiratory syndrome virus (PRRSV) exhibits extensive genetic variation. The outbreak of a highly pathogenic PRRS in 2006 led us to investigate the extent of PRRSV genetic diversity in China. To this end, we analyzed the Nsp2 and ORF7 gene sequences of 98 Chinese PRRSV isolates.</p> <p>Results</p> <p>Preliminary analysis indicated that highly pathogenic PRRSV strains with a 30-amino acid deletion in the Nsp2 protein are the dominant viruses circulating in China. Further analysis based on ORF7 sequences revealed that all Chinese isolates were divided into 5 subgroups, and that the highly pathogenic PRRSVs were distantly related to the MLV or CH-1R vaccine, raising doubts about the efficacy of these vaccines. The ORF7 sequence data also showed no apparent associations between geographic or temporal origin and heterogeneity of PRRSV in China.</p> <p>Conclusion</p> <p>These findings enhance our knowledge of the genetic characteristics of Chinese PRRSV isolates, and may facilitate the development of effective strategies for monitoring and controlling PRRSV in China.</p

In-vitro and in-vivo phenotype of type Asia 1 foot-and-mouth disease viruses utilizing two non-RGD receptor recognition sites

<p>Abstract</p> <p>Background</p> <p>Foot-and-mouth disease virus (FMDV) uses a highly conserved Arg-Gly-Asp (RGD) triplet for attachment to host cells and this motif is believed to be essential for virus viability. Previous sequence analyses of the 1D-encoding region of an FMDV field isolate (Asia1/JS/CHA/05) and its two derivatives indicated that two viruses, which contained an Arg-Asp-Asp (RDD) or an Arg-Ser-Asp (RSD) triplet instead of the RGD integrin recognition motif, were generated serendipitously upon short-term evolution of field isolate in different biological environments. To examine the influence of single amino acid substitutions in the receptor binding site of the RDD-containing FMD viral genome on virus viability and the ability of non-RGD FMDVs to cause disease in susceptible animals, we constructed an RDD-containing FMDV full-length cDNA clone and derived mutant molecules with RGD or RSD receptor recognition motifs. Following transfection of BSR cells with the full-length genome plasmids, the genetically engineered viruses were examined for their infectious potential in cell culture and susceptible animals.</p> <p>Results</p> <p>Amino acid sequence analysis of the 1D-coding region of different derivatives derived from the Asia1/JS/CHA/05 field isolate revealed that the RDD mutants became dominant or achieved population equilibrium with coexistence of the RGD and RSD subpopulations at an early phase of type Asia1 FMDV quasispecies evolution. Furthermore, the RDD and RSD sequences remained genetically stable for at least 20 passages. Using reverse genetics, the RDD-, RSD-, and RGD-containing FMD viruses were rescued from full-length cDNA clones, and single amino acid substitution in RDD-containing FMD viral genome did not affect virus viability. The genetically engineered viruses replicated stably in BHK-21 cells and had similar growth properties to the parental virus. The RDD parental virus and two non-RGD recombinant viruses were virulent to pigs and bovines that developed typical clinical disease and viremia.</p> <p>Conclusions</p> <p>FMDV quasispecies evolving in a different biological environment gained the capability of selecting different receptor recognition site. The RDD-containing FMD viral genome can accommodate substitutions in the receptor binding site without additional changes in the capsid. The viruses expressing non-RGD receptor binding sites can replicate stably in vitro and produce typical FMD clinical disease in susceptible animals.</p

Prognostic risk factors of pneumonia associated with COVID-19 in patients with lymphoma

ObjectivePatients with hematological malignancies have an elevated risk of developing pneumonia after contracting COVID-19. Lymphoma is the most prevalent hematologic malignancy. It is critical to identify patients at high risk of contracting COVID-19-associated pneumonia.MethodsFrom January 11–31, 2023, we distributed questionnaires to patients diagnosed with lymphoma according to 2016 World Health Organization diagnostic and classification criteria. COVID-19 infection was confirmed based on symptoms and laboratory tests. Pneumonia was confirmed using computed tomography scans.ResultsIn total, 257 patients were included in this study; 221 patients (86.0%) had COVID-19 infection and 61 (27.6%) of these had pneumonia. Patients with B-cell non-Hodgkin lymphoma (B-NHL) had a significantly higher pneumonia incidence than patients with other lymphoma types (31.8% vs. 27.6%, P=0.005). Higher incidence of pneumonia was observed in patients receiving anti-CD20 therapy (30.0% vs. 16.3%, P=0.048) and Bruton’s tyrosine kinase (BTK) inhibitor therapy (51.3% vs. 22.5%, P=0.001). B-NHL (hazard ratio [HR]=3.7, 95% confidence interval [CI] 1.4–10.0, P=0.009), anti-CD20 therapy (HR=2.3, 95% CI 1.0–5.2, P=0.050), BTK inhibitor (HR=3.6, 95% CI 1.8–7.4, P&lt;0.001), active therapy (HR=3.0, 95% CI 1.5–5.7, P=0.001), and lack of disease remission (HR=3.7, 95% CI 1.8–7.4, P=0.001) were high-risk factors for developing pneumonia. Anti-PD-1 therapy was a protective factor against pneumonia development (HR=0.2, 95% CI 0.05–0.9, P=0.034). In multivariable analysis, BTK inhibitor (HR=3.5, 95% CI 1.6–8.0, P=0.003), active therapy (HR=3.3, 95% CI 1.6–6.8, P=0.001), and disease non-remission (HR=2.9, 1.3–6.4, P=0.007) were independent risk factors for pneumonia development after COVID-19 infection in patients with lymphoma.ConclusionsPatients with lymphoma receiving BTK inhibitors, undergoing active therapy, and lacking disease remission exhibited a higher risk for pneumonia associated with COVID-19

Whole-genome analysis of the recombination and evolution of newly identified NADC30-like porcine reproductive and respiratory syndrome virus strains circulated in Gansu province of China in 2023

Porcine reproductive and respiratory syndrome virus (PRRSV) remains one of the major threats to swine industry, resulting in huge economic losses worldwide. Currently, PRRSV has diversified into multiple lineages with characteristics of extensive recombination in China. In this research, three virus strains were isolated and four virus whole genome sequences were generated and analyzed from clinical samples collected in Gansu province of China in 2023. The four virus strains were designated GSTS4-2023, GSLX2-2023, GSFEI2-2023 and GSBY4-2023. Phylogenetic analysis based on ORF5 sequences showed that GSTS4-2023, GSLX2-2023, GSFEI2-2023 and GSBY4-2023 shared 91.7, 91.2, 93.2 and 92.9% homology with NADC30 strain respectively, and belonged to lineage 1 of PRRSV-2. In addition, one amino acid deletion was observed at position 33 in ORF5 of GSTS4-2023, GSLX2-2023 and GSFEI2-2023. Moreover, amino acid alignment of the four strains showed a typical discontinuous 131-amino acid (aa) deletion in NSP2 for NADC30-like virus strains. Recombination analysis revealed that all four strains originated from NADC30 (lineage 1), with their minor parents coming from JXA1-like strains (lineage 8), VR-2332-like strains (lineage5) and QYYZ-like strains (lineage3). Finally, the three isolated virus strains, GSTS4-2023, GSLX2-2023 and GSFEI2-2023 showed relatively low levels of replication in cell culture. Our findings provide important implications for the field epidemiology of PRRSV