China Expert consensus on the application of metagenomic next-generation sequencing for the etiological diagnosis of infections in hematological disorders (2024).

Infections are frequent complications in patients with hematological disorders, and pathogen diagnosis remains challenging. Metagenomic next-generation sequencing (mNGS) is an unbiased high-throughput technology that has been widely applied in the diagnosis of infectious diseases. However, to date, there are no established international guidelines or expert consensuses regarding the use of mNGS to diagnose infections in patients with hematologic disorders.

Epidemiology, Clinical Features, and Molecular Basis of TTMV::RARA-driven Acute Promyelocytic Leukemia.

Integration of torque teno mini virus (TTMV) generating the TTMV::RARA fusion represents a newly recognized subtype of acute promyelocytic leukemia (APL) that merits detailed investigation. We present the first comprehensive characterization of its epidemiologic profile, clinical presentation, virologic characteristics, and underlying molecular mechanisms. Our findings indicate that TTMV::RARA is more prevalent in pediatric patients and represents the second most common retinoic acid receptor fusion after PML::RARA.

Permeable Hydrogel Encapsulated Osteosarcoma-on-a-Chip for High-Throughput Multi-Drugs Screening.

Pharmacological chemotherapy remains a cornerstone in treating osteosarcoma (OS), where the application of drug combinations not only enhances therapeutic efficacy but also mitigates adverse side effects. However, the absence of an efficient and reliable drug screening platform poses a significant challenge in optimizing these combination therapies. In this study, we introduce a novel OS chip designed to facilitate the high-throughput and precise evaluation of drug combination efficacy, addressing this critical gap in OS treatment research.

Efficacy and Safety of BCMA Nanobody CAR-T Cell Therapy in Relapsed or Refractory Plasma Cell Myeloma.

BCMA CAR-T has demonstrated promising therapeutic efficacy in refractory and relapsed multiple myeloma. However, distinct CAR-T constructs exhibit varying therapeutic outcomes. As the antigen recognition domain, nanobodies offer a small, stable, single-domain structure with enhanced affinity and specificity compared to conventional scFv fragments.

Reduced nephrin tyrosine phosphorylation impairs podocyte force transmission and accelerates detachment in disease.

Podocytes are specialized kidney cells that form the slit diaphragm (SD), an intercellular filtration barrier against plasma protein loss. The SD is subject to significant mechanical strain which can be amplified in disease, leading to podocyte detachment. One key SD protein that might intercept mechanical strain and transmit adhesion signals is nephrin, although its influence on podocyte force transmission remains uncharacterized.

SOHO State of the Art Updates and Next Questions | CD7 CAR-T Therapy for Treating CD7-Positive Hematological Malignancies: Clinical Advances and Future Directions.

CD7 CAR-T cell therapy has emerged as a promising treatment for relapsed/refractory (R/R) CD7-positive hematological malignancies, offering new hope for patients with limited therapeutic options. This review examines the recent clinical advances, challenges, and future directions of CD7 CAR-T therapy. Clinical trials have demonstrated remarkable efficacy of CD7 chimeric antigen receptor T (CD7 CAR-T) cells in treating T-cell acute lymphoblastic leukemia (T-ALL), T-cell lymphoblastic lymphoma (T-LBL), and other CD7-positive malignancies, with complete remission (CR) rates of 90-95% in bone marrow (BM) and 50% to 60% in extramedullary disease (EMD).

Early Detection of Malignant Cells in Gastric Lavage via Hexokinase 2 and Single-Cell Sequencing for Gastric Cancer Diagnosis.

Objective: Gastric cancer represents a significant global health challenge due to its high prevalence and mortality rates, largely attributed to the limitations of current screening methods, such as endoscopy, which impede early diagnosis. This study presents an innovative method for early detection by identifying exfoliated tumor cells in gastric lavage, aiming to overcome challenges related to patient compliance and the variability in endoscopist expertise.

Methods: Hexokinase 2 (HK2), a metabolic marker, was utilized to identify exfoliated tumor cells with heightened glycolytic activity in gastric lavage fluid.

Comparable survival outcomes in HLA-Matched and haploidentical hematopoietic stem cell transplantation for severe aplastic anemia patients aged 40-50: A CBMTR Registry-based propensity score matching analysis over the last decade.

Our study includes 278 patients aged between 40 and 50 years from 29 centers who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) from matched sibling donors (MSDs) (n = 106) and haploidentical donors (HIDs) (n = 172) over the last decade. Univariate analysis revealed that HID recipients was associated with more serious disease severity, a delayed allo-HSCT after diagnosis, a higher pretransplant transfusion burden and poor performance status pre-transplant than MSD recipients in clinical settings. After these pretransplant clinical factors were well balanced following propensity score-matching (PSM), 80 matched pairs were selected for further analysis.

Dynamic Tumor Immunology-on-a-Chip for Peripheral Blood-Derived Tumor-Reactive T Cell Expansion.

Adoptive T cell therapy has shown great promise in the treatment of solid tumors, which, however, poses a great challenge to obtain autologous tumor-reactive T cells in a cost-effective manner. Here, we present a dynamic tumor immunology-on-a-chip, mimicking immune responses, for achieving the enrichment and expansion of tumor-reactive T cells. Tumor spheroids with uniform size can be generated by seeding tumor cells in hydrogel-embedded micropillar arrays, and could be trapped upon removal of hydrogel.

Peripheral blood CD8 + CD28+ T cells as predictive biomarkers for treatment response in metastatic colorectal cancer.

Background: Colorectal cancer (CRC) is a substantial global health burden, with treatment outcomes significantly influenced by the interaction between the immune system and the tumor microenvironment.

Objective: This study aims to investigate the role of peripheral blood immune cell subpopulations, particularly CD8+ CD28+ T cells, in predicting treatment response in metastatic CRC patients receiving bevacizumab combined with chemotherapy.

Methods: A cohort of 45 CRC patients was analyzed.

Neo-BCV: A Novel Bacterial Liquid Complex Vaccine for Enhancing Dendritic Cell-Mediated Immune Responses Against Lung Cancer.

Background: In the past decade, immunotherapy has become a major choice for the treatment of lung cancer, yet its therapeutic efficacy is still relatively limited due to the various immune escape mechanisms of tumors. Based on this, we introduce Neo-BCV, a novel bacterial composite vaccine designed to enhance immune responses against lung cancer.

Methods: We investigated the immune enhancing effect of Neo-BCV through in vivo and in vitro experiments, including flow cytometry, RNA-seq, and Western blot.

Evaluation of the Clinical Safety of the Low-Cost Warburg Therapy for the Treatment of Patients With Advanced Cancers.

Background: Rising cancer care costs are becoming cost prohibitive for lower income people worldwide. We developed the Warburg protocol as a low-cost option for the treatment of cancer that was inspired. It was developed to exploit an Achilles heel which is a hallmark of cancer cells; the metabolic requirement for higher levels of glucose than normal cells.

Nanobody-based naturally selected CD7-targeted CAR-T therapy for acute myeloid leukemia.

Approximately 30% of patients with acute myeloid leukemia (AML) express CD7 on their myeloblasts. We have previously demonstrated that single-chain variable fragment (scFv)-based "naturally selected" CD7 chimeric antigen receptor T-cell (NS7CAR-T) therapy shows significant efficacy, with a favorable safety profile in T-cell lymphoid malignancies. Here, we derived dual variable heavy-chain domain of a heavy-chain antibody (dVHH) NS7CAR-Ts that have superior CD7 binding specificity, affinity to their scFv-based counterparts, and improved proliferative capability.

Ruxolitinib plus steroids for acute graft versus host disease: a multicenter, randomized, phase 3 trial.

Newly diagnosed patients with high-risk acute graft-versus-host disease (aGVHD) often experience poor clinical outcomes and low complete remission rates. Ruxolitinib with corticosteroids showed promising efficacy in improving response and failure free survival in our phase I study. This study (ClinicalTrials.

Swin-PSAxialNet: An Efficient Multi-Organ Segmentation Technique.

Abdominal multi-organ segmentation is one of the most important topics in the field of medical image analysis, and it plays an important role in supporting clinical workflows such as disease diagnosis and treatment planning. In this study, an efficient multi-organ segmentation method called Swin-PSAxialNet based on the nnU-Net architecture is proposed. It was designed specifically for the precise segmentation of 11 abdominal organs in CT images.

A safety and efficacy study of allogeneic haematopoietic stem cell transplantation for refractory and relapsed T-cell acute lymphoblastic leukaemia/lymphoblastic lymphoma patients who achieved complete remission after autologous CD7 chimeric antigen receptor T-cell therapy.

CD7-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown promising initial complete remission (CR) rates in patients with refractory or relapsed (r/r) T-cell acute lymphoblastic leukaemia and lymphoblastic lymphoma (T-ALL/LBL). To enhance the remission duration, consolidation with allogeneic haematopoietic stem cell transplantation (allo-HSCT) is considered. Our study delved into the outcomes of 34 patients with r/r T-ALL/LBL who underwent allo-HSCT after achieving CR with autologous CD7 CAR-T therapy.

Targeting nucleotide metabolic pathways in colorectal cancer by integrating scRNA-seq, spatial transcriptome, and bulk RNA-seq data.

Background: Colorectal cancer is a malignant tumor of the digestive system originating from abnormal cell proliferation in the colon or rectum, often leading to gastrointestinal symptoms and severe health issues. Nucleotide metabolism, which encompasses the synthesis of DNA and RNA, is a pivotal cellular biochemical process that significantly impacts both the progression and therapeutic strategies of colorectal cancer METHODS: For single-cell RNA sequencing (scRNA-seq), five functions were employed to calculate scores related to nucleotide metabolism. Cell developmental trajectory analysis and intercellular interaction analysis were utilized to explore the metabolic characteristics and communication patterns of different epithelial cells.

Advances towards genome-based acute myeloid leukemia classification: A comparative analysis of WHO-HAEM4R, WHO-HAEM5, and International Consensus Classification.

Two recent guidelines, the 5th edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO-HAEM5) and the International Consensus Classification (ICC), were published to refine the diagnostic criteria of acute myeloid leukemia (AML). They both consider genomic features more extensively and expand molecularly defined AML subtypes. In this study, we compared the classifications of 1135 AML cases under both criteria.

Clinical markers predict the efficacy of several immune checkpoint inhibitors in patients with non-small cell lung cancer in China.

Objectives: Immune checkpoint inhibitors (ICIs) are one of the most significant oncological treatment modalities as a result of the rapid advancement of immunotherapy. Programmed Cell Death-Ligand 1 (PD-L1) and tumor mutational burden (TMB) have emerged as key markers for predicting the efficacy and prognosis of ICIs in non-small cell lung cancer (NSCLC), and the predictive role of tumor-infiltrating lymphocytes (TILs) has also received significant attention. However, the prognosis of some individuals cannot be determined by these indicators; for instance, some patients with low PD-L1 expression also benefit from longer survival.

Analysis of 60 patients with relapsed or refractory T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma treated with CD7-targeted chimeric antigen receptor-T cell therapy.

While the use of chimeric antigen receptor-T (CAR-T) therapy for T-cell malignancies is in the early stage of clinical trials, it exhibits substantial potential to offer long-term remission for patients with refractory/relapsed (R/R) T-cell malignancies. In our phase I/II clinical trials, 65 pediatric and adult patients with R/R T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma (T-ALL/LBL) were enrolled (NCT04572308 and NCT04916860). Of these, 60 participants (T-ALL 35, T-LBL 25) received a single dose of naturally selected anti-CD7 CAR (NS7CAR) T cells at three levels: a low dose (5 × 10 /kg), a medium dose (1 to 1.