Paediatric-inspired regimen reduces central nervous system relapse in adult acute lymphoblastic leukaemia.

Central nervous system (CNS) is the common site of extramedullary relapse in adult acute lymphoblastic leukaemia (ALL) and the outcome of CNS relapse patients remains poor. This study aimed to investigate whether a paediatric-inspired chemotherapy regimen can reduce CNS relapse in adult ALL compared to the adult regimen. A total of 1005 newly diagnosed adult patients with ALL were enrolled in this study, including 596 patients who received the Hyper-CVAD (cyclophosphamide, vincristine, doxorubicin[adriamycin], and dexamethason) adult regimen and 409 patients who treated with the Precision Classification-Directed Target Total Therapy-ALL-2016 (PDT-ALL-2016) paediatric-inspired chemotherapy regimen.

Efficacy and safety of third-generation CD19-CAR T cells incorporating CD28 and TLR2 intracellular domains for B-cell malignancies with central nervous system involvement: results of a pivotal trial.

Background: Third‑generation CAR-T cells demonstrated promising efficacy and remarkably low toxicity in refractory or relapsed (R/R) B-cell malignancies. However, data on the patients with central nervous system (CNS) involvement are limited due to concerns regarding treatment-related neurotoxicity. This study aimed to evaluate the safety and efficacy of a novel third-generation anti-CD19 CAR T cells in patients with CNS involvement of B-cell malignancies.

Interleukin-21 engineering enhances CD19-specific CAR-NK cell activity against B-cell lymphoma via enriched metabolic pathways.

Background: NK cells engineered to express interleukin-15 (IL-15) and a CD19-targeted chimeric antigen receptor (CAR) have been used to treat patients with relapsed and/or refractory B cell malignances, demonstrating encouraging outcomes and favorable safety profile. However, the effect of IL-21 in CAR-NK cell therapy remains unknown.

Methods: CD19-specific CAR with 4-1BB costimulatory domain and cytokine IL-21 or IL-15 was constructed and transduced into peripheral blood (PB)-derived NK cells to produce CD19-CAR-IL21 NK cells (CAR-21) or CD19-CAR-IL15 NK cells (CAR-15), respectively.

EDN1 and NTF3 in keloid pathogenesis: computational and experimental evidence as novel diagnostic biomarkers for fibrosis and inflammation.

Objective: To investigate the roles of oxidative stress-related differentially expressed genes (OSRDEGs) in keloid formation and explore their potential value in diagnosis and treatment.

Methods: Gene expression data from the GEO database, including GSE145725 and GSE44270 as training sets and GSE7890 as a validation set, were utilized. OSRDEGs were identified, followed by Weighted Gene Co-expression Network Analysis (WGCNA), GO/KEGG enrichment analysis, and Gene Set Enrichment Analysis (GSEA).

Tucidinostat plus pediatric-inspired chemotherapy for newly diagnosed adult ETP-ALL/LBL: a single-arm, phase 2 trial.

Early T-cell precursor lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) is a distinct subtype of T-ALL/LBL, characterized by a poor response to initial chemotherapy, a high relapse rate, and an inferior outcome. The treatment options for ETP-ALL/LBL are currently limited, and there are no reported clinical trials available for ETP-ALL/LBL. From June 2018 to June 2022, we conducted a single-arm, single-center, phase 2 trial (NCT03553238) in newly diagnosed ETP-ALL/LBL (age 14-55).

Efficacy of NKG2D CAR-T cells with IL-15/IL-15Rα signaling for treating Epstein-Barr virus-associated lymphoproliferative disorder.

Epstein-Barr virus (EBV) related post-transplant lymphoproliferative disorder (EBV-PTLD) is a life-threatening complication after hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT), for which no standard therapeutic means have been developed. Significant increase expression of natural killer group 2 member D ligands (NKG2DLs) was observed on B-lymphoblastoid cells of EBV-PTLD, indicating NKG2DLs as potential therapeutic targets for treatment of EBV-PTLD. In this study, the recombinant constructs of NKG2D CAR and IL-15/IL-15Rα-NKG2D CAR were generated with a retroviral vector and then transduced to human T cells to produce NKG2D CAR-T and IL-15/IL-15Rα-NKG2D CAR-T cells, respectively.

Preference of consumers for higher-grade energy-saving appliances in hierarchical Chinese cities.

Promotion of energy-saving household appliances (ESHAs) potentially contributes to optimizing both the total quantity and efficiency of household energy consumption. Differences in urban consumers' preference for higher-grade ESHAs as well as its influencing factors in cities with hierarchical socioeconomic levels remain elusive. Targeting 55 Chinese cities pertaining to three levels of socioeconomic development, we distribute questionnaires designed to cover both demographic and consciousness factors.

Cytokines induced memory-like NK cells engineered to express CD19 CAR exhibit enhanced responses against B cell malignancies.

CD19 chimeric antigen receptor (CAR) engineered NK cells have been used for treating patients with relapsed and/or refractory B cell malignancies and show encouraging outcomes and safety profile. However, the poor persistence of NK cells remains a major challenge for CAR NK cell therapy. Memory-like NK cells (MLNK) induced by IL-12, IL-15, and IL-18 have shown enhanced and prolonged responses to tumor re-stimulation, making them an attractive candidate for adoptive cellular immunotherapy.

Interaction of glioma-associated microglia/macrophages and anti-PD1 immunotherapy.

Anti-PD-1-based therapy has resulted in a minimal clinical response in malignant gliomas. Gliomas contain numerous glioma-associated microglia/macrophages (GAMs), reported to contribute to an immunosuppressive microenvironment and promote glioma progression. However, whether and how GAMs affect anti-PD-1 immunotherapy in glioma remains unclear.

PD-1H Expression Associated With CD68 Macrophage Marker Confers an Immune-Activated Microenvironment and Favorable Overall Survival in Human Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal carcinoma (EC) in China. Although the PD-1 inhibitor pembrolizumab has been approved to treat patients with EC, its therapeutic efficacy is limited. Thus, additional immunotherapeutic targets for EC treatment are needed.

Sensitivity and Specificity of CD19.CAR-T Cell Detection by Flow Cytometry and PCR.

Chimeric-antigen-receptor-T (CAR-T) cells are currently revolutionizing the field of cancer immunotherapy. Therefore, there is an urgent need for CAR-T cell monitoring by clinicians to assess cell expansion and persistence in patients. CAR-T cell manufacturers and researchers need to evaluate transduction efficiency and vector copy number for quality control.

RTN3 inhibits RIG-I-mediated antiviral responses by impairing TRIM25-mediated K63-linked polyubiquitination.

Upon viral RNA recognition, the RIG-I signalosome continuously generates IFNs and cytokines, leading to neutrophil recruitment and inflammation. Thus, attenuation of excessive immune and inflammatory responses is crucial to restore immune homeostasis and prevent unwarranted damage, yet few resolving mediators have been identified. In the present study, we demonstrated that RTN3 is strongly upregulated during RNA viral infection and acts as an inflammation-resolving regulator.

A Real-Time Stability Control Method Through sEMG Interface for Lower Extremity Rehabilitation Exoskeletons.

Herein, we propose a real-time stable control gait switching method for the exoskeleton rehabilitation robot. Exoskeleton rehabilitation robots have been extensively developed during the past decade and are able to offer valuable motor ability to paraplegics. However, achieving stable states of the human-exoskeleton system while conserving wearer strength remains challenging.

A novel HDAC inhibitor chidamide combined with imatinib synergistically targets tyrosine kinase inhibitor resistant chronic myeloid leukemia cells.

Chidamide is a novel selective histone deacetylase inhibitor (HDACi) with promising activity in hematological malignancies, but its role in chronic myeloid leukemia (CML) was marginally addressed. In this study, we firstly demonstrated that chidamide alone inhibited CML cells proliferation, induced apoptosis and cell cycle arrest. Further, chidamide combined with imatinib (IM) induced synergistic lethality in CML cell line KBM5, as well as IM-resistant CML cells KBM5, associated with a marked reduction of Bcr-Abl kinase activity and acetyl-histone H3 expression.

B7-H3 specific T cells with chimeric antigen receptor and decoy PD-1 receptors eradicate established solid human tumors in mouse models.

The application of chimeric antigen receptor (CAR)-T cell therapy in patients with advanced solid tumors remains a significant challenge. Simultaneously targeting antigen and the solid tumor microenvironment are two major factors that greatly impact CAR-T cell therapy outcomes. In this study, we engineered CAR-T cells to specifically target B7-H3, a protein commonly found in solid human tumors, using a single-chain variable fragment (scFv) derived from an anti-B7-H3 monoclonal antibody.

Chimeric Antigen Receptor (CAR) T Cell Therapy in Acute Myeloid Leukemia (AML).

Despite high response rates after initial chemotherapy in patients with acute myeloid leukemia (AML), relapses occur frequently, resulting in a five-year-survival by <30% of the patients. Hitherto, allogeneic hemotopoietic stem cell transplantation (allo-HSCT) is the best curative treatment option in intermediate and high risk AML. It is the proof-of-concept for T cell-based immunotherapies in AML based on the graft-versus-leukemia (GvL)-effect, but it also bears the risk of graft-versus-host disease.

Mesenchymal stem cells participate in oral mucosa carcinogenesis by regulating T cell proliferation.

Recent evidences suggested that Mesenchymal stem cells (MSCs) may be involved in tumor formation by modulating of the tumor microenvironment, but it is still unclear the potential of MSCs in the malignant transformation of oral mucosa. Using a chemically-induced oral carcinogenesis model by 4-nitroquinoline-1-oxide (4NQO), we generated precancerous lesions and cancerous lesions in the oral cavity of rats. Flow cytometric analysis on lesions derived single cell suspension revealed an increase in the proportion of MSCs and a decreased proportion of T cell during oral mucosa malignancy.

A crucial role of the PD-1H coinhibitory receptor in suppressing experimental asthma.

Programmed death one homolog (PD-1H) is a cell surface molecule of the B7/CD28 immune modulatory gene family. Although PD-1H has been shown to function as a coinhibitory receptor on T cells to limit naive T-cell activation and proliferation, its role in the regulation of the T-cell response to allergens is unknown. We report here that genetic ablation or blockade of PD-1H drastically promotes pulmonary inflammation with massive accumulation of eosinophils in a mouse model of experimental asthma, indicating a suppressive function of PD-1H in allergic inflammation.