Juan Ouyang

Background: Multiple myeloma (MM) is an incurable hematologic malignancy, and the majority of patients eventually relapse due to persistent myeloma cells. While minimal residual disease (MRD) reflects tumor burden, the host immune system also plays a crucial role in disease control. Our study aimed to evaluate MRD, complete blood count (CBC), and immune cell profiles in MM patients treated with bortezomib/adriamycin/dexamethasone (PAD) chemotherapy followed by autologous stem cell transplantation (ASCT) to determine their prognostic value and interplay. Objectives: This study aims to identify markers indicative of a favorable prognosis in MM patients. Methods: CBC data were collected from 93 MM patients at diagnosis, prior to ASCT, and 3 months post-ASCT. Immune cell profiles were assessed via flow cytometry using fresh peripheral blood samples from a subset of 33 prior to ASCT and 3 months post-ASCT. We subsequently investigated the associations between MRD status and prognosis, the predictive value of CBC, and the longitudinal changes in immune cell profiles and their correlation with clinical outcomes. Results: An increased frequency of negative immunomodulatory cell subsets and activated T lymphocytes prior to ASCT were associated with a poor prognosis. Conversely, lower levels of exhausted T lymphocytes, alongside higher levels of functional T cells and marginal zone B cells post-ASCT, predicted a favorable prognosis. Conclusions: Our study demonstrates that pre-ASCT immune status, post-ASCT immune reconstitution, and MRD status at 3 months post-ASCT are closely associated with clinical outcomes in MM patients. These findings underscore the critical importance of regular immune monitoring in the comprehensive management of MM.

Background: Non‐anemic thalassemia trait (TT) accounted for a high proportion of TT cases in South China. Objective: To use artificial intelligence (AI) analysis of erythrocyte morphology and machine learning (ML) to identify TT gene carriers in a non‐anemic population. Methods: Digital morphological data from 76 TT gene carriers and 97 controls were collected. The AI technology‐based Mindray MC‐100i was used to quantitatively analyze the percentage of abnormal erythrocytes. Further, ML was used to construct a prediction model. Results: Non‐anemic TT carriers accounted for over 60% of the TT cases. Random Forest was selected as the prediction model and named TT@Normal. The TT@Normal algorithm showed outstanding performance in the training, validation, and external validation sets and could efficiently identify TT carriers in the non‐anemic population. The top three weights in the TT@Normal model were the target cells, microcytes, and teardrop cells. Elevated percentages of abnormal erythrocytes should raise a strong suspicion of being a TT gene carrier. TT@Normal could be promoted and used as a visualization and sharing tool. It is accessible through a URL link and can be used by medical staff online to predict the possibility of TT gene carriage in a non‐anemic population. Conclusions: The ML‐based model TT@Normal could efficiently identify TT carriers in non‐anemic people. Elevated percentages of target cells, microcytes, and teardrop cells should raise a strong suspicion of being a TT gene carrier.

We developed an artificial intelligence (AI) model that evaluates the feasibility of AI-assisted multiparameter flow cytometry (MFC) diagnosis of acute leukemia. Two hundred acute leukemia patients and 94 patients with cytopenia(s) or hematocytosis were selected to study the AI application in MFC diagnosis of acute leukemia. The kappa test analyzed the consistency of the diagnostic results and the immunophenotype of acute leukemia. Bland–Altman and Pearson analyses evaluated the consistency and correlation of the abnormal cell proportion between the AI and manual methods. The AI analysis time for each case (83.72 ± 23.90 s, mean ± SD) was significantly shorter than the average time for manual analysis (15.64 ± 7.16 min, mean ± SD). The total consistency of diagnostic results was 0.976 (kappa (κ) = 0.963). The Bland–Altman evaluation of the abnormal cell proportion between the AI analysis and manual analysis showed that the bias ± SD was 0.752 ± 6.646, and the 95% limit of agreement was from −12.775 to 13.779 (p = 0.1225). The total consistency of the AI immunophenotypic diagnosis and the manual results was 0.889 (kappa, 0.775). The consistency and speedup of the AI-assisted workflow indicate its promising clinical application.

OBJECTIVE: The aim of the present study was to investigate the mechanism of homocysteine (Hcy) induced oxidative stress in the human umbilical vein endothelial cells (HUVECs). PATIENTS AND METHODS: The HUVECs were isolated from umbilical vein vascular wall of 12 patients and treated with Hcy. The malondialdehyde (MDA) level was measured using the thiobarbituric acid (TBA) method. The expressions of superoxide dismutase 2 (SOD2), endothelial nitric oxide synthase (eNOS), and intercellular adhesion molecule 1 (ICAM-1) were detected by Western blot and RT-PCR. The genome-wide DNA methylation assay was performed using the Infinium Human Methylation 450 BeadChip. The specific DNA methylation was determined using bisulfite sequencing analysis. To evaluate the role of sorbin and SH3 domain-containing protein 1 (SORBS1), the HUVECs were transfected with small interfere RNA (siRNA) targeting SORBS1 (SORBS1-siRNA). RESULTS: Hcy induced MDA level in HUVECs, and increased ICAM-1 expression both in protein and mRNA levels. The protein and mRNA levels of SOD2 and eNOS were inhibited by Hcy induction. However, the effects of Hcy on MDA level and expressions of SOD2, eNOS, and ICAM-1 were attenuated by folic acid (Fc) and vitamin B12 (B12) treatment. DNA total methylation level in Hcy treated cells was significantly decreased compared to the control group, while the DNA total methylation levels were increased after treatment with Fc and B12. The methylation level of SORBS1 in Hcy treatment group was higher than that of control group. And the methylation level of SORBS1 induced by Hcy was attenuated by Fc and B12 treatment. SORBS1-siRNA transfection induced the MDA levels and reduced the expressions of SOD2 in HUVECs. CONCLUSIONS: We indicated that Hcy induced oxidative stress in HUVECs via regulating methylation of SORBS1. We also found that Fc and B12 treatment attenuated the oxidative stress and inflammation induced by Hcy in HUVECs. The findings indicated that Fc and B12 might be effective agents for the treatment of Hcy induced AS.

Purpose Glucocorticoids (GCs) are of wide usage in the clinical treatment of lymphoblastic malignancies such as acute lymphoblastic leukemia. However, individually distinctive responsiveness to the GC therapy may attenuate their clinical efficacy, and more reliable predictor for GC resistance is still eagerly needed. Recent studies indicate that microRNAs (miRNAs), which demonstrate regulatory functions targeting mRNAs during the post-transcription, involved in the regulation of GCs sensitivity through several mechanisms, especially adjusting the magnitude of GC receptors (GRs), which mediates the cellular effects of GCs and plays a pivotal role in GCs sensitivity, inspiring that special miRNAs pattern could serve as the biomarkers to predict GC sensitivity and bring forth potential strategies for overcoming drug resistance. In this review, we discuss related miRNAs and their diverse effects exerted on multifaceted complexity of GCs responsiveness for further exploiting the molecular mechanism of GC resistance and future construction of the molecular diagnostic method and reverse GC resistance. Methods We have reviewed and searched for eligible literature relating to the effects of microRNAs on GC responsiveness from systematic PubMed searches. Results GC response can be mediated by miRNAs through influence on GC signaling pathway, leading to diverse glucocorticoid responsiveness. Mutations in miRNA gene also influence GC response. As well, GCs regulate the function of several miRNAs, and suggesting a bidirectional influence among them. Conclusions It is possible and necessary that miRNAs serve as stable biomarkers and GC resistant patients would benefit from an effective and early screening test.