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Biomedical subjects

Ping An

Publications and source records attributed to Ping An.

2 recordsLinked to original sources

Recombinant Human Thrombopoietin Reduces the Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia.

Chronic liver disease (CLD)-related thrombocytopenia can limit the feasibility of invasive procedures. Recombinant human thrombopoietin (rhTPO) has demonstrated a favorable safety profile without hepatotoxicity. We evaluated the efficacy and safety of rhTPO in patients with CLD-related thrombocytopenia who were undergoing elective invasive procedures. In this multicenter, randomized (2:1), double-blind, placebo-controlled phase III trial, 120 adult Chinese patients with CLD-related thrombocytopenia (platelet count <&#x2009;50 &#xd7;&#x2009;109/L) received rhTPO (n =&#x2009;80) or placebo (n =&#x2009;40) once daily for up to 5 or 7&#x2009;days. The primary endpoint was the proportion of patients with sustained platelet counts &#x2265;&#x2009;50 &#xd7;&#x2009;109/L from 24 h before invasive procedure to 7&#x2009;days post-procedure, without requiring emergency bleeding management. The primary endpoint was achieved by 85.0% of patients in the rhTPO group versus 12.5% in the placebo group (p&#x2009;<&#x2009;0.0001). Preoperatively, platelet counts &#x2265;&#x2009;50 &#xd7;&#x2009;109/L were achieved in 92.5% and 20.0% of patients in the rhTPO and placebo groups, respectively (p&#x2009;<&#x2009;0.0001). Platelet transfusion was avoided in 92.5% of rhTPO-treated patients versus 25.0% of placebo-treated patients (p&#x2009;<&#x2009;0.0001). The median duration of platelet counts &#x2265;&#x2009;50 &#xd7;&#x2009;109/L was significantly longer with rhTPO than with placebo (21.0 vs. 3.0&#x2009;days, p =&#x2009;0.0007). Treatment-related treatment-emergent adverse events (TEAEs) occurred in 12.5% of patients in both the rhTPO and placebo groups. No treatment-related serious adverse events were reported. Overall, rhTPO was effective and well tolerated in patients with CLD-related thrombocytopenia and may represent a viable therapeutic option for those undergoing elective invasive procedures. Trial Registration: www.chinadrugtrials.org.cn: number CTR20230919.

Humans

Single-cell profiling reveals epithelial and immune responses in BK polyomavirus-infected human kidney biopsies.

INTRODUCTIONBK polyomavirus (BKV) infection is associated with injury and subsequent graft loss due to the extent of injury or rejection. However, the molecular mechanisms driving injury and subsequent adverse outcomes remain poorly understood.METHODSIn a cross-sectional study, single-cell RNA-seq from kidney allograft biopsies was used to assess cell type-specific responses between uninfected controls and 2 distinct phases of BKV infection: peaking (increasing viral blood titers) and resolving (decreasing viral titers following immunosuppression reduction).RESULTSGenes upregulated in BK viral nephropathy (BKVN) were enriched for polyomavirus infection hallmarks, including ribosome biogenesis, translation, and energy restructuring. Additionally, enriched pathways included wound healing, cellular stress, antigen presentation and immune signaling. Even without BKVN (peaking BK viremia alone), epithelial cells expressed signatures for wound healing, cellular stress, and extracellular matrix remodeling. In vivo tubular cell responses at single-cell resolution were validated against single cell transcriptomic data of BKV-infected cells in a cell culture model. Despite similarities, in vivo tubular cells underwent metabolic adaptation favoring fatty acid oxidation and proinflammatory responses not observed in culture models, likely due to an absent innate and adaptive immune system. Despite lymphopenia and immunosuppressive therapies, the proportion of recipient-derived intrarenal adaptive immune cells was increased in biopsies associated with peaking viremia alongside activation of innate immune responses. Adaptive immune cells exhibited persistent inflammatory signaling and remodeling of energy metabolism during the resolving phase of infection.CONCLUSIONThese not previously reported insights into BKV-associated injury may have implications for clinical management and improved allograft outcomes.

Humans