Apmis最新文献

This study was to evaluate the sufficient safety and effect of the novel influenza vaccine program. It prepared new reassortant influenza virus, with high yield on Vero cells. According to the plaque counting, one dose LAIV was composed with 10⁵ PFU of H1, H3, BY, and BV, respectively. Then mixed this LAIV with compound adjuvant, containing 500 μg/mL of carbopol971P and 50 μg/mL of tetanus toxin. That vaccination was called catt-flu. And it employed the GYZZ02 vaccine (commercialized freeze-dried LAIV, listed in China) as cohort analysis control. All mice received two doses of the vaccine, administered on days 0 and 14, respectively. That catt-flu program could induce more cross-protection with neutralizing antibody against heterogeneous types of influenza virus, not only based on HA but also NA protective antigen, through convenient nasal immunization, which had non-inferiority titter compared with the chicken embryo-derived GYZZ02 vaccine on safe and effect. The Vero cell-derived vaccine (LAIV) combined compound catt adjuvant (contain carbopol971P and tetanus toxin) could provide another safety and protective program of influenza vaccine by intranasal administration, as catt-flu program.

SARS-CoV-2 variants of concern (VOC), such as Delta and Omicron have harbored mutations, which increased viral infectivity or ability to evade neutralizing antibodies. Immunocompromised patients might be a source of some of these emerging variants. In this study, we sequenced 17 consecutive samples from an immunocompromised patient with a long-term SARS-CoV-2 infection with the pre-VOC era lineage B.1.177.35. We here describe the emergence of 73 nonsynonymous minority variants in this patient and show that 10 of these mutations became dominant in the viral population during the treatment period. Four of these were seen throughout the infection period and had a very low global prevalence, although three of them were also observed later in the Alpha, Delta, and Omicron lineages. We also found that two adjacent nsp12 variants (M785I and S786P) belonged to different quasi-species and competed during the early stages of infection and remdesivir administration. This emphasizes the importance of ongoing genome surveillance of SARS-CoV-2 among immunocpromised patients.

Ki-67, a nuclear protein expressed in all stages of cellular proliferation, is a valuable tool to assess tumor proliferation and has been linked to more aggressive tumor behavior. However, interlaboratory staining heterogeneity and inter-observer variability challenge its reproducibility. Round Robin tests are a suitable tool to standardize and harmonize immunohistochemical and molecular analyses in histopathology. The study investigates the interrater and interlaboratory reproducibility of Ki-67-scoring using both manual and automated approaches. Unstained TMA slides comprising diverse tumor types (breast cancer, neuroendocrine tumors, lymphomas, and head and neck squamous cell carcinoma) were distributed to six pathology laboratories, each employing their routine staining protocols. Manual and automated scoring methods were applied, and interrater and interlaboratory agreement assessed using intraclass correlation coefficients (ICC). The results highlight good-to-excellent reliability overall, with automated scoring demonstrating higher consistency (ICC 0.955) than manual scoring (ICC 0.871). Results were more variable when looking at the individual entities. Reliability remained good for lymphomas (ICC 0.878) and breast cancer (ICC 0.784) and was poor in well-differentiated neuroendocrine tumors (ICC 0.354). This study clearly advocates standardized practices and training to ensure consistency in Ki-67-assessment, and it demonstrates that this can be achieved in a peer-to-peer approach in local quality-circles.

Cancer-associated fibroblasts (CAFs) are crucial component of tumor microenvironment (TME) which undergo significant phenotypic changes and metabolic reprogramming, profoundly impacting tumor growth. This review delves into CAF plasticity, diverse origins, and the molecular mechanisms driving their continuous activation. Emphasis is placed on the intricate bidirectional crosstalk between CAFs and tumor cells, promoting cancer cell survival, proliferation, invasion, and immune evasion. Metabolic reprogramming, a cancer hallmark, extends beyond cancer cells to CAFs, contributing to the complex metabolic interplay within the TME. The ‘reverse Warburg effect’ in CAFs mirrors the Warburg effect, involving the export of high-energy substrates to fuel cancer cells, supporting their rapid proliferation. Molecular regulations by key players like p53, Myc, and K-RAS orchestrate this metabolic adaptation. Understanding the metabolic symbiosis between CAFs and tumor cells opens avenues for targeted therapeutic strategies to disrupt this dynamic crosstalk. Unraveling CAF-mediated metabolic reprogramming provides valuable insights for developing novel anticancer therapies. This comprehensive review consolidates current knowledge, shedding light on CAFs' multifaceted roles in the TME and offering potential targets for future therapies.

An observational and retrospective study was carried out to analyse HCoV positivity from a multiplex PCR respiratory panel and RT-PCR for SARS-CoV-2 in respiratory samples from 1 June 2020 to 31 July 2023 at the Príncipe de Asturias University Hospital (HUPA) in Alcalá de Henares, Madrid, Spain. Out of 2802 respiratory panels, 1258 (44.8%) turned out positive. HCoV was detected in 114 (4%) cases (range 0–23; median 1.5; IQR 0–3.75) with positivity rates ranging from 0% to 14%. All four variants of HCoV circulated, and OC-43 was the most common in 62.3% of cases. After the onset of the pandemic, the HCoV season was delayed 22 weeks, with a peak positivity of 9% in the summer of 2021, showing an inverse relationship with the alpha and delta waves of SARS-CoV-2. In the two subsequent autumn–winter seasons, HCoV positivity increased (11–14%) with a reduction in the summer of 2022 and 2023 following the emergence of the omicron variant and the relaxation of social distancing measures. The seasonal spread pattern of endemic HCoV might be returning to normal in our region and likely in other temperate zones of the northern hemisphere after 3 years of the pandemic.

Fifteen percent of all colorectal cancers have detectable defects in the mismatch repair system (dMMR). MMR status is used to identify possible Lynch Syndrome (LS) and to determine prognosis and choice of treatment. Two standard techniques for determining MMR status are immunohistochemistry (IHC) and analysis for microsatellite instability (MSI) by PCR. Recently, our department introduced Idylla™ MSI assay as an alternative option to IHC, and as part of this, we introduced a decision algorithm. The purpose of this study was to review the use of the new method and our algorithm and to assess possible false-positive results. Retrospectively, we identified 629 cases of colorectal cancer in which either IHC (336 cases) or Idylla™ MSI (293 cases) was performed. Similar results were obtained by the two methods. IHC detected dMMR in 55 cases (16%) and Idylla™ MSI in 52 cases (18%). In all 52 cases of MSI, subsequent IHC was performed. One case was not confirmed by IHC, but was confirmed by another PCR-based method. Overall, we found that the Idylla™ MSI works well as a screening method for dMMR with no false-positive cases detected. The proposed algorithm was useful and easily applicable.

The study aimed to investigate the expression profiles of transcription factors, cytokines, and co-stimulatory molecules in helper T (Th)-cell subsets within bronchoalveolar lavage (BAL) samples of patients with interstitial lung diseases (ILDs). Twenty ILDs patients were included in the study, comprising those with idiopathic pulmonary fibrosis (IPF) (n:8), autoimmune-related ILDs (auto-ILD) (n:4), and orphan diseases (O-ILD) (n:8), alongside five control subjects. Flow cytometry was employed to evaluate the Th to cytotoxic T cell (CTL) ratio in BAL fluid, while cytopathological examination assessed macrophages, lymphocytes, and neutrophils. Quantitative real-time polymerase chain reaction was utilized to investigate the expressions in Th1, Th2, Th17, and regulatory T (Treg) cells. Results revealed elevated Th cell to CTL ratios across all patient groups compared to controls. Furthermore, upregulation of Th1, Th2, Th17, and T-cell factors was observed in all patient groups compared to controls. Interestingly, upregulation of CD28 and downregulation of CTLA-4 and PD-1 gene expression were consistent across all ILDs groups, highlighting potential immune dysregulation. This study provides a comprehensive exploration of molecular immunological mechanisms in ILDs patients, underscoring the dominance of Th2 and Th17 responses and revealing novel findings regarding the dysregulation of CD28, CTLA-4, and PD-1 expressions in ILDs for the first time.

Pseudomonas aeruginosa infection causes pneumonia and sepsis. Previous research found that X-ray radiation can induce P. aeruginosa to release outer membrane vesicles (OMVs) of relatively consistent sizes. This study found that OMVs derived from X-ray-irradiated P. aeruginosa can significantly inhibit lung leakage, inflammatory cell infiltrating into lung, and the production of pro-inflammatory cytokines, IL-1β and TNFα caused by P. aeruginosa infection under preventive and therapeutic administration conditions. Under the same conditions, OMVs also significantly alleviated pathological characteristics of lung injury, including pulmonary edema, pulmonary hemorrhage, and alveolar wall thickening. OMVs also significantly reduced bacterial burdens in peritoneal cavity, accompanied by a reduction in the number of viable bacteria capable of forming bacterial colonies. Pretreating macrophages and neutrophils with OMVs enhances their bactericidal ability. When bacteria were cocultured with treated cells, the number of viable bacteria capable of forming bacterial colonies was significantly reduced. OMVs themselves have not been shown to cause any lung injury or affect bacterial viability. Therefore, OMVs derived from X-ray-irradiated P. aeruginosa may not only be applied in prevention and treatment of diseases associated with P. aeruginosa infection, but also served as an excellent vaccine development platform.

Acute encephalitis syndrome (AES) is a major public health concern in India as the aetiology remains unknown in the majority of cases with the current testing algorithm. We aimed to study the incidence of Japanese encephalitis (JE) and determine the aetiology of non-JE AES cases to develop an evidence-based testing algorithm. Cerebrospinal fluid (CSF) samples were tested for Japanese encephalitis virus by ELISA and polymerase chain reaction (PCR). Multiplex real-time PCR was done for Dengue, Chikungunya, West Nile, Zika, Enterovirus, Epstein Barr Virus, Herpes Simplex Virus, Adenovirus, Cytomegalovirus, Herpesvirus 6, Parechovirus, Parvovirus B19, Varicella Zoster Virus, Scrub typhus, Rickettsia species, Leptospira, Salmonella species, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Plasmodium species and by ELISA for Mumps and Measles virus. Of the 3173 CSF samples, 461 (14.5%) were positive for JE. Of the 334 non-JE AES cases, 66.2% viz. Scrub typhus (25.7%), Mumps (19.5%), Measles (4.2%), Parvovirus B19 (3.9%) Plasmodium (2.7%), HSV 1 and 2 (2.4%), EBV and Streptococcus pneumoniae (2.1% each), Salmonella and HHV 6 (1.2% each) were predominant. Hence, an improved surveillance system and our suggested expanded testing algorithm can improve the diagnosis of potentially treatable infectious agents of AES in India.

The clinical data from 118 CTD patients with bronchiectasis were collected and categorized into two groups: pulmonary infection present (n = 67) and absent (n = 51), for comparative analysis of characteristics and risk factors. Then, we analyzed and compared their demographics, disease characteristics, and risk factors for infection. Among the whole cohort (n = 118), the incidence of pulmonary infections was 56.78%. The occurrence of rheumatoid arthritis, systemic lupus erythematosus, and vasculitis was found to be associated with an increased risk of pulmonary infection. Sputum culture identified Pseudomonas aeruginosa and Klebsiella pneumoniae as the predominant pathogens in the infected group. Notably, symptoms such as joint pains (p = 0.018) and morning stiffness (p = 0.017) were significantly more common in the infected group compared to the noninfected group. Moreover, our findings revealed that elevated levels of C-reactive protein and complement C3, along with bronchial expansion observed on high-resolution computed tomography (HRCT), were significant independent factors in the infection group. Conversely, pulmonary interstitial changes identified through HRCT (OR: 0.135, 95% CI: 0.030–0.612, p = 0.009) were significantly associated with the non-infection group. Overall, this study provides valuable insights into managing CTD patients with bronchiectasis, emphasizing early detection and tailored approaches to prevent and treat pulmonary infections for better outcomes.