Background and objective:The purpose of this investigation is to develop and test a new computer aided detection (CAD) scheme which is able to identify the residual cancer cells from the digitalized clinical specimens for the prognostic assessment of leukemia/lymphoma.Methods: First, a whole slide image scan was performed by a commercialized fluorescent microscopic image scanner equipped with an objective 40× lens.Then, a computerized scheme was applied to detect and segment all clinically analyzable interphase cells depicted on the scanned images, as well as to recognize and count the independent FISH-probed signal dots within each interphase cell.Five pathological specimens were used to test the performance of this new scheme. Results:The result shows that our scheme segmented and analyzed 4546, 3807, 2880, 2240, and 849 analyzable cells in five slides of different specimens including blood, bone marrow samples respectively, among which 334, 405, 178, 117, and 24 cells are detected by the scheme as suspiciously abnormal (or residual malignant) cells. Conclusions:Comparing to the current visual detection method, the CAD scheme identified a much larger amount of FISH-probed cells.This investigation may help more sensitively detect residual cancer cells and improve the accuracy of prognostic assessment for leukemia/lymphoma patients in the future.
The L1 cell adhesion molecule (L1CAM) is a protein encoded by a gene that has been localized to Xq28, is a member of the immunoglobulin superfamily of neuronal cell adhesion molecules, and plays a role in CNS development and maturation. L1CAM is expressed in neurons and Schwann cells, where it is active in neurite overgrowth, adhesion fasciculation, migration, myelination, and axon guidance. Mutations within the gene have been associated with phenotypic changes that include hydrocephalus due to aqueductal stenosis, agenesis or hypoplasia of the corpus callosum and corticospinal tracts, mental retardation, spastic paraplegia, and adducted thumbs. Here, we present a 19-year-old primigravida Caucasian woman who was referred to us in the 27th week of the pregnancy because of fetal polyhydramnios and ventriculomegaly. Our evaluation identified a male fetus with hydrocephalus, ventriculomegaly, aqueductal stenosis, and polyhydramnios. An amniocentesis was performed, and isolated fetal DNA revealed a hemizygous G > C mutation in codon 2809 of exon 21 of the L1CAM gene. The patient was later tested and identified to be a carrier of the same mutation. The fetus was delivered during the 38th week. Neonatal physical examination revealed marked frontal bossing, contractures of the feet with rocker bottom appearance, and hyperactive reflexes with ankle and knee clonus. He died at 4 months of life.
MYCN amplification directly correlates with the clinical course of neuroblastoma and poor patient survival, and serves as the most critical negative prognostic marker. Although fluorescence in situ hybridization (FISH) remains the gold standard for clinical diagnosis of MYCN status in neuroblastoma, its limitations warrant the identification of rapid, reliable, less technically challenging, and inexpensive alternate approaches. In the present study, we examined the concordance of droplet digital PCR (ddPCR, in combination with immunohistochemistry, IHC) with FISH for MYCN detection in a panel of formalin-fixed paraffin-embedded (FFPE) human neuroblastoma samples. In 112 neuroblastoma cases, ddPCR analysis demonstrated a 96–100% concordance with FISH. Consistently, IHC grading revealed 92–100% concordance with FISH. Comparing ddPCR with IHC, we observed a concordance of 95–98%. The results demonstrate that MYCN amplification status in NB cases can be assessed with ddPCR, and suggest that ddPCR could be a technically less challenging method of detecting MYCN status in FFPE specimens. More importantly, these findings illustrate the concordance between FISH and ddPCR in the detection of MYCN status. Together, the results suggest that rapid, less technically demanding, and inexpensive ddPCR in conjunction with IHC could serve as an alternate approach to detect MYCN status in NB cases, with near-identical sensitivity to that of FISH.
Objective To investigate the probability of hepatocellular carcinoma (HCC) in a large number of gray-zone (GZ) patients with chronic hepatitis B (CHB) in clinical practice. Methods The patients with CHB who were diagnosed and treated in our hospital from January 2013 to January 2023 were analyzed retrospectively. Results According to the different levels of HBeAg, ALT and HBV DNA, GZ patients were divided into four categories: (1) Gray zone A (GZ-A): HBeAg positive, normal ALT level, HBV DNA ≤ 10 6 IU/ml; (2) Gray zone B (GZ-B): HBeAg positive, ALT>ULN, HBV DNA ≤ 2 × 10 4 IU/ml; (3) Gray zone C (GZ-C): HBeAg negative, normal ALT level, HBV DNA ≥ 2 × 10 3 IU/ml; and (4) Gray zone D (GZ-D): HBeAg negative, ALT > ULN, serum HBV DNA ≤ 2 × 10 3 IU/ml. This observational study showed that after adjustment using inverse probability of treatment weighting (IPTW), the probability of developing HCC in the GZ group was similar to that in the immune-tolerant, HBeAg-positive immune active, and inactive groups. The IPTW-adjusted analysis revealed that the probability of developing HCC in the GZ-B subgroup was similar to that in the immune-active and HBeAg-negative immune-active groups. Conclusion The GZ group and GZ-B subgroup have a higher risk of HCC. Anti-hepatitis B virus therapy should be considered as early as possible for patients in the GZ group, especially in the GZ-B subgroup.
Pulmonary fibrosis (PF) leads to chronic inflammation and accumulation of macrophages, neutrophils, and lymphocytes in the alveoli. The factors involved in the development of PF include reactive oxygen species and tissue remodelling regulators. The present study demonstrates the effect of andrographolide on bleomycin (BLM)-induced PF in Sprague-Dawley rats. We investigated the total bronchoalveolar lavage fluid protein (BALF) and hydroxyproline (HYP) content along with the level of oxidative stress markers like malondialdehyde (MDA) and GSH/GSSG ratio. In addition, the levels of MMP-1 and TIMP-1 were also analysed. The results revealed an increase in BALF protein, HYP, and MDA contents and decrease in GSH/GSSG ratio of the lungs in animals treated with BLM. However, andrographolide treatment caused a reversal of the BLM induced changes after 20 or 40 days. Treatment with andrographolide suppressed oxidative stress with the decrease of MDA and the increase of the GSH/GSSG ratio. Andrographolide also improved the BLM mediated changes in the MMP-1/TIMP-1 ratio. Therefore, andrographolide has a potential therapeutic effect in the prevention of PF.
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