Safety and efficacy of CD19-targeted CAR-T-cell therapy for patients with relapsed or refractory TCF3-PBX1 fusion gene-positive B-ALL.

Chimeric antigen receptor (CAR)-T therapy has shown significant success in the treatment of relapsed or refractory acute lymphoblastic leukemia (r/r ALL). However, its role in patients with the TCF3-PBX1 fusion gene - which generally exhibit poor prognostic indicators - remains uncertain. From September 2016 to March 2023, 7 patients with r/r ALL positive for the TCF3-PBX1 fusion gene underwent CD19 CAR-T-cell therapy at the First Affiliated Hospital of Zhejiang University School of Medicine.

Safety and efficacy of autologous humanized CD19 CAR-T cell therapy for relapsed/refractory B-cell non-Hodgkin lymphoma.

Chimeric antigen receptor (CAR)-T cells have made great progress in hematological malignancies and optimization of CAR structure is a critical area of exploration. Limited research has evaluated humanized CD19-targeted CAR-T cells (hCART19) in relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). We conducted a clinical trial to determine the safety of hCART19 for patients with R/R B-NHL.

The isolation and immunoprotective efficacy of outer membrane vesicles of Dichelobacter nodosus.

Dichelobacter nodosus is a major causative agent of infectious foot diseases in ruminants, responsible for substantial economic losses globally in the livestock industry. The development of a vaccine is therefore of great importance. In this study, we employed density gradient ultracentrifugation to extract outer membrane vesicles (OMVs) from D.

Characterization of the Na-preferential transporter HKT1.1 from halophyte shrub .

Unlabelled: Soil salinity is one of the main environmental limiting factors for plant growth and production. Sodium salt (NaCl) is the main salt in saline soils. The high-affinity K transporter (HKT1) is a Na-preferential transporter identified in multiple glycophyte plants, and it participates in salt tolerance through shoot Na extrusion.

OsWRKY18, a WRKY transcription factor, is involved in rice salt tolerance.

Salinity stress significantly impairs plant growth and leads to substantial yield losses in rice and other crops. WRKY transcription factors (TFs) are well-documented regulators of plant stress responses, yet their specific roles in rice salt tolerance remain largely unexplored. This study investigates the function of OsWRKY18, a rice WRKY TF with transcriptional activation activity, in salt stress adaptation.

On-treatment serum albumin levels can predict 28-day mortality and guide albumin infusion in sepsis patients.

Background: As the most abundant protein in plasma, albumin (ALB) presents close association with prognosis of septic patients. Whereas, the benefit and the target level of ALB infusion remain controversial.

Methods: We conducted a retrospective investigation to assess whether on-treatment ALB levels could predict 28-day mortality and try to identify the optimal level for ALB infusion.

Dasatinib and CAR T-Cell Therapy in Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Nonrandomized Clinical Trial.

Importance: A combination of tyrosine kinase inhibitors and chimeric antigen receptor (CAR) T cells has made a breakthrough in refractory or relapsed Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). However, it remains unclear if this treatment in newly diagnosed Ph-positive ALL is associated with high rates of complete molecular remission (CMR) and leukemia-free survival.

Objective: To evaluate the efficacy and safety of dasatinib in combination with CAR T cells as frontline therapy in adults with newly diagnosed Ph-positive ALL.

Long-term follow-up of BCMA CAR-T cell therapy in patients with relapsed/refractory multiple myeloma.

Background: B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T-cell immunotherapy has shown promising results in the treatment of relapsed or refractory multiple myeloma (R/RMM). This study presents the updated long-term outcomes from our center.

Methods: Between July 30, 2018, and September 27, 2023, 141 patients with R/RMM who received BCMA CAR-T therapy were enrolled.

Analysis of the prognostic efficacy of syndecan-1 for patients with ACLF and its functional role in liver regeneration.

Background: Acute-on-chronic liver failure (ACLF) is a syndrome characterized by systemic inflammation with a high short-term mortality rate. Syndecan-1 (SDC-1) can independently predict the 90-day mortality of patients with septic shock. However, the role of SDC-1 in ACLF remains unknown.

Sequential allogeneic HSCT after CAR-T therapy for relapsed/refractory acute lymphoblastic leukemia patients: A long-term follow-up result.

Introduction: CAR-T cell therapy has revolutionized the therapeutic landscape for relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), and bridging with allogeneic hematopoietic stem cell transplantation (allo-HSCT) has the potential to lower relapse rates. Nevertheless, the majority of existing studies have exclusively focused on short-term outcomes, resulting in a lack of comprehensive understanding of the long-term sustainability of overall prognosis.

Objectives: Our study aimed to provide real-world, long-term follow-up data for patients who underwent sequential therapy.

Scientometric analysis of research trends in hemorrhagic fever with renal syndrome: A historical review and network visualization.

Background: Hemorrhagic fever with renal syndrome (HFRS) research has undergone significant global transformation over the past decades. A comprehensive scientometric overview of research trends and scholarly cooperation in HFRS is absent. This study employs scientometric analysis to map the evolution of research themes, identify widely and scarcely explored areas, and anticipate future research directions.

Ultra-small quercetin-based nanotherapeutics ameliorate acute liver failure by combatting inflammation/cellular senescence cycle.

Acute liver failure (ALF) is marked by a substantial generation of reactive oxygen species (ROS), which can induce both cellular senescence and a pronounced inflammatory response. Senescent cells secrete factors collectively termed the senescence-associated secretory phenotype (SASP), which exacerbate inflammation, while inflammation can reciprocally promote cellular senescence. Quercetin (Que), recognized for its ROS-scavenging capabilities, holds the potential for anti-inflammatory and anti-senescent effects.

Prominent efficacy and good safety of sequential CD19 and CD22 CAR-T therapy in relapsed/refractory adult B-cell acute lymphoblastic leukemia.

Background: Sequential CD19 and CD22 chimeric antigen receptor (CAR)-T cell therapy offers a promising approach to antigen-loss relapse in relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL); however, research in adults remains limited.

Methods: This study aimed to evaluate the efficacy and safety of sequential CD19 and CD22 CAR-T cell therapy in adult patients with R/R B-ALL between November 2020 and November 2023 (ChiCTR2100053871). Key endpoints included the adverse event incidence, overall survival (OS), and leukemia-free survival (LFS).

Osteogenesis promotion on MC3T3 by micro-area potential difference (MAPD) on titanium alloy.

The ability of osseointegration of implants is an important factor in ensuring the long-term stability of bone implants in their recipient sites. In this paper, Ti-M titanium alloys with different surface micro-area potential difference (MAPD) were prepared and the adhesion, proliferation, spreading, and differentiation behavior of osteoblasts (MC3T3) on the surface of Ti-M alloy were investigated in detail to reveal the effect of MAPD on cell compatibility and osteogenic differentiation. The results showed that the alloy with high MAPD facilitated bone differentiation, demonstrating that MAPD significantly enhanced the alkaline phosphatase activity and mineralization ability of osteoblasts, and upregulated the expression of osteogenic differentiation-related factors.

Predictive value of pre-treatment circulating tumor DNA genomic landscape in patients with relapsed/refractory multiple myeloma undergoing anti-BCMA CAR-T therapy: Insights from tumor cells and T cells.

Background: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM.

Methods: Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential.

Pilots' Reactions to Different Types of Alerts When Using Head-Up Displays.

The benefits of using head-up displays (HUDs) include reducing head-down time during critical flight phases, enhancing awareness of the external environment, and improving in-flight crew performance. However, the monochromatic nature of HUDs, increased head rotation, and longer gaze movement paths might affect pilots' reactions to different types of alerts. Pilot workload and behavior differences were examined between HUD and head-down display (HDD) configurations in three alert scenarios.

Sequential CD7 CAR T-Cell Therapy and Allogeneic HSCT without GVHD Prophylaxis.

Background: Patients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects.

C/EBPα-p30 confers AML cell susceptibility to the terminal unfolded protein response and resistance to Venetoclax by activating DDIT3 transcription.

Background: Acute myeloid leukemia (AML) with biallelic (CEBPA) as well as single mutations located in the bZIP region is associated with a favorable prognosis, but the underlying mechanisms are still unclear. Here, we propose that two isoforms of C/EBPα regulate DNA damage-inducible transcript 3 (DDIT3) transcription in AML cells corporately, leading to altered susceptibility to endoplasmic reticulum (ER) stress and related drugs.

Methods: Human AML cell lines and murine myeloid precursor cell line 32Dcl3 cells were infected with recombinant lentiviruses to knock down CEBPA expression or over-express the two isoforms of C/EBPα.

Cytokine-based models for efficient differentiation between infection and cytokine release syndrome in patients with hematological malignancies.

Although the efficacy of chimeric antigen receptor (CAR)-T cell therapy has been widely demonstrated, its clinical application is hampered by the complexity and fatality of its side effects. Cytokine release syndrome (CRS) is the most common toxicity following CAR-T cell infusion, and its symptoms substantially overlap with those of infection. Whereas, current diagnostic techniques for infections are time-consuming and not highly sensitive.

Platelet-derived microparticles adoptively transfer integrin β3 to promote antitumor effect of tumor-infiltrating T cells.

Approximately two-thirds of hepatocellular carcinoma (HCC) is considered a "cold tumor" characterized by few tumor-infiltrating T cells and an abundance of immunosuppressive cells. Cilengitide, an integrin αvβ3 inhibitor, has failed in clinical trials as a potential anticancer drug. This failure implies that integrin αvβ3 may play an important role in immune cells.

Relapsed/Refractory Peripheral T-Cell Lymphoma-Associated Hemophagocytic Lymphohistiocytosis With UNC13D and CD27 Germline Mutations.

Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory disease characterized by familial and acquired forms. Here, we present the case of a 26-year-old male patient with relapsed/refractory peripheral T-cell lymphoma and concurrent HLH. Whole-exon sequencing revealed germline mutations associated with HLH, including those in critical genes such as and and other germline heterozygous variants (, and ).

Treatment with β-Adrenoceptor Agonist Isoproterenol Reduces Non-parenchymal Cell Responses in LPS/D-GalN-Induced Liver Injury.

There is an increasing evidence indicating the involvement of the sympathetic nervous system (SNS) in liver disease development. To achieve an extensive comprehension of the obscure process by which the SNS alleviates inflammatory damage in non-parenchymal liver cells (NPCs) during acute liver failure (ALF), we employ isoproterenol (ISO), a beta-adrenoceptor agonist, to mimic SNS signaling. ISO was administered to C57BL/6J mice to establish an acute liver failure (ALF) model using LPS/D-GalN, which was defined as ISO + ALF.

Cholinergic Anti-inflammatory Pathway Attenuates Acute Liver Failure Through Inhibiting MAdCAM1/α4β7-mediated Gut-derived Proinflammatory Lymphocytes Accumulation.

Background & Aims: The function of cholinergic anti-inflammatory pathway (CAP) in acute liver failure (ALF) with inflammatory storm remains indefinite. The liver-gut axis has been proved to be crucial for liver homeostasis. Investigation about CAP regulation on liver-gut axis would enrich our understanding over cholinergic anti-inflammatory mechanism.

The outer membrane protein of Fusobacterium necrophorum, 43K OMP, stimulates inflammatory cytokine production through nuclear factor kappa B activation.

Objective: Fusobacterium necrophorum causes bovine hepatic abscess, foot rot, mastitis, and endometritis. The 43 kDa outer membrane protein (43 K OMP) of F. necrophorum is a porin protein that plays an important role in infections by this bacterium, but the biological function and the pathogenesis of this protein are largely unknown.