A global study for acute myeloid leukemia with RARG rearrangement.

Acute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to alltrans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four patients with AML with RARG rearrangements were identified. Bleeding or ecchymosis was present in 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and 26.5% of the cases, respectively. Immunophenotyping showed the following characteristics: positive for CD33, CD13, and MPO but negative for CD38, CD11b, CD34, and HLA-DR. Cytogenetics showed normal karyotype in 38% and t(11;12) in 26% of patients. The partner genes of RARG were diverse and included CPSF6, NUP98, HNRNPc, HNRNPm, PML, and NPM1. WT1- and NRAS/KRAS-mutations were common comutations. None of the 34 patients responded to ATRA and/or ATO. Death within 45 days from diagnosis occurred in 10 patients (∼29%). At the last follow-up, 23 patients had died, and the estimated 2-year cumulative incidence of relapse, event-free survival, and overall survival were 68.7%, 26.7%, and 33.5%, respectively. Unsupervised hierarchical clustering using RNA sequencing data from 201 patients with AML showed that 81.8% of the RARG fusion samples clustered together, suggesting a new molecular subtype. RARG rearrangement is a novel entity of AML that confers a poor prognosis. This study is registered with the Chinese Clinical Trial Registry (ChiCTR2200055810).

Novel insight from the first lung transplant of a COVID-19 patient.

BACKGROUND: To reveal detailed histopathological changes, virus distributions, immunologic properties and multi-omic features caused by SARS-CoV-2 in the explanted lungs from the world's first successful lung transplantation of a COVID-19 patient. MATERIALS AND METHODS: A total of 36 samples were collected from the lungs. Histopathological features and virus distribution were observed by optical microscope and transmission electron microscope (TEM). Immune cells were detected by flow cytometry and immunohistochemistry. Transcriptome and proteome approaches were used to investigate main biological processes involved in COVID-19-associated pulmonary fibrosis. RESULTS: The histopathological changes of the lung tissues were characterized by extensive pulmonary interstitial fibrosis and haemorrhage. Viral particles were observed in the cytoplasm of macrophages. CD3+ CD4- T cells, neutrophils, NK cells, γ/δ T cells and monocytes, but not B cells, were abundant in the lungs. Higher levels of proinflammatory cytokines iNOS, IL-1ß and IL-6 were in the area of mild fibrosis. Multi-omics analyses revealed a total of 126 out of 20,356 significant different transcription and 114 out of 8,493 protein expression in lung samples with mild and severe fibrosis, most of which were related to fibrosis and inflammation. CONCLUSIONS: Our results provide novel insight that the significant neutrophil/ CD3+ CD4- T cell/ macrophage activation leads to cytokine storm and severe fibrosis in the lungs of COVID-19 patient and may contribute to a better understanding of COVID-19 pathogenesis.

A Gold Nanoparticle Bouquet held on plasma membrane: An ultrasensitive dark-field imaging approach for Cancer Cell Analysis.

Rational: p53 is suppressing tumor protein correlated with the cell cycle factors and apoptosis. Here, a gold nanoparticle bouquet is designed for an ultrasensitive dark-field imaging approach for cancer cell analysis. Methods: AuNP60/APBA is functionalized by a gold nanoparticle bouquet-plasmonic 60 nm gold nanoparticles. And consistent APBA can be held on the plasma membrane. After 13 nm gold nanoparticles are functionalized with mannose (AuNP13/MN), the AuNP60/APBA gold nanoparticles are captured. The absorption spectrum of aggregation gold nanoparticles (AuNPs) shifts to near-infrared (NIR) region which can be observed under dark-field microscopy (DFM) and is treated the subsequent with photothermal therapy. Results: The results that MCF-7 cells were successfully destroyed under the near-infrared (NIR) irradiation and the intracellular WTp53 increased while the MTp53 decreased. These results indicated that p53 is the key molecule in the apoptosis signaling pathway. Photothermal therapy can stimulate the MTp53 in the cell signal conductive pathway. Conclusion: This work offers a new method for intracellular p53 analysis and a potential targeted cancer treatment.

Effect of VEGF, P53 and telomerase on angiogenesis of gastric carcinoma tissue.

OBJECTIVE: To investigate the effect of vascular endothelial growth factor (VEGF), P53 and telomerase on angiogenesis in gastric carcinoma tissue. METHODS: A total of 95 surgical resection samples of gastric cancer tissue after pathological diagnosis are collected to observe the VEGF, P53 and telomerase expression using immunohistochemical methods. Relationship between their expression and its influence on angiogenesis in gastric carcinoma tissue were analyzed. RESULTS: Microvascular density (MVD) and the expression of VEGF, P53 and telomerase were positively correlated. Expression of VEGF and P53 protein were related to tumor type and lymph metastasis, and also a correlation was observed between P53 and VEGF. The telomerase expression had no correlation with VEGF, and P53. CONCLUSIONS: VEGF angiogenesis has a angiogenesis promoting effect on gastric cancer tissue development and plays an important role in tumor generation and metastasis. Mutant P53 promotes the tumor angiogenesis generation by adjusting VEGF. Telomerase has a certain role in promoting activity of angiogenesis through different way rather than P53.

[Central mechanisms of masticatory muscle pain induced by occlusal interference].

OBJECTIVE: To study c-fos and substance P expression in the central nervous system following mechanical and chemical nociceptive stimulation to the masseters in rats with occlusal interference. METHODS: Occlusal interference was made by bonding a 2 mm long dentin screw in the pulp cavity of the first maxillary molar in the left side. Seven days after occlusal interference, the rats in occlusal interference and mechanical stimulus group and mechanical stimulus control group were light anesthetized and nociceptive mechanical stimulus were applied to the ipsilateral masseter. Pain response was recorded and all the animals were killed 2 hours later. The rats in the other two groups were deep anesthetized and 100 microL 5% formalin was injected into the ipsilateral masseter, killed 2 hours later. The brainstem and cervical spinal cord were processed c-fos and substance P immunoreactivity and data were quantitatively analyzed. RESULTS: Both mechanical and chemical stimulus to the ipsilateral masseter induced increasing neuronal c-fos expression in the trigeminal nucleus and in the cervical spinal dorsal horn in occlusal interference and mechanical stimulus group and occlusal interference and chemical stimulus group (P < 0.05). Following mechanical stimulation to the ipsilateral masseter, substance P expression in the trigeminal nucleus transition zone was increased in occlusal interference and mechanical stimulus group (P < 0.05). CONCLUSION: The central neuronal sensitization in the brainstem may play an important role in the masticatory muscle pain induced by occlusal interference.

[Myelodysplastic syndrome with early presentation of refractory monolineage cytopenia-with report of 13 cases].

To find the relationship between myelodysplastic syndrome (MDS) and refractory monolineage cytopenia, thirteen cases of MDS with early presentation of monolineage refractory cytopenia were analyzed retrospectively. The results were as follows: (1) The percentage of 13 cases with refractory monolineage cytopenia were 5.9% of the total 219 MDS patients in the past 10 years. (2) The median time of patients with monlineage cytopenia to M DS diagnosed was 48.5 +/- 55.3 months. The median times from monolineage cytopenia to MDS diagnosed for patients with neutropenia, erythrocytopenia and thrombocytopenia were 12.5 +/- 9.5 months, 53.8 +/- 54.6 months and 59.2 +/- 65.5 months, respectively. (3) The common characteristics of 13 cases were as follows: (a) the macrocytic erythrocytes in peripheral blood and the percentage of intermediate and late erythroblast in bone marrow were increased; (b) occasionally few cells with dysplasia could be found; (c) all patients with erythrocytopenia and thrombocytopenia transformed to RA and RAS while the most of patients with neutropenia transformed to RAEB subtype; (d) autoantibody could be found in part of the patients. It is concluded that some of refractory monolineage cytopenias in essence are the early states of MDS.