Aging-induced IL27Ra signaling impairs hematopoietic stem cells.

Hematopoietic stem cell (HSC) aging correlates with an increasing risk of myeloproliferative disease and immunosenescence. In this study, we show that aging-related inflammation promotes HSC aging through tumor necrosis factor-α (TNF-α)→ERK→ETS1→interleukin27Ra (IL27Ra) pathway. TNF-α, a well-known biomarker of inflammation, increases during aging and induces the expression of IL27Ra on HSCs via ERK-ETS1 signaling.

Haploidentical donor is preferred over matched sibling donor for pre-transplantation MRD positive ALL: a phase 3 genetically randomized study.

Background: Previous reports suggest a benefit associated with haploidentical donor transplantation (HIDT) compared to matched sibling donor transplantation (MSDT) in certain contexts, and the choice of optimal candidates warrants further investigation.

Methods: We designed a prospective genetically randomized study to evaluate donor options between acute lymphoblastic leukemia (ALL) patients positive for measurable residual disease (MRD) pre-transplantation who underwent HIDT (n = 169) or MSDT (n = 39).

Results: The cumulative incidence of positive MRD post-transplantation was 26% (95% CI, 19-33%) and 44% (95% CI, 28-60%) for HIDT and MSDT, respectively (P = 0.

Lupus low disease activity state as a treatment endpoint for systemic lupus erythematosus: a prospective validation study.

Background: Treat-to-target strategies have improved outcomes in single-organ diseases with simple clinical or laboratory endpoints. A lack of validated endpoints has prevented adoption of treat to target for complex multiorgan conditions, such as systemic lupus erythematosus (SLE). We report the first prospective study undertaken to specifically validate a treat-to-target endpoint for SLE.

Evaluation of remission definitions for systemic lupus erythematosus: a prospective cohort study.

Background: Validated outcome measures are needed from which to derive treatment strategies for systemic lupus erythematosus (SLE). However, no definition of remission for SLE has been widely adopted. The Definitions of Remission in Systemic Lupus Erythematosus (DORIS) group has proposed a framework with multiple potential definitions of remission.

The Quantification of Minimal Residual Disease Pre- and Post-Unmanipulated Haploidentical Allograft by Multiparameter Flow Cytometry in Pediatric Acute Lymphoblastic Leukemia.

Background: This study aimed to determine the impact of the pre- and post-minimal residual disease (MRD) status as well as the peri-transplant MRD kinetics on clinical outcomes in pediatric ALL patients who received haploidentical allografts.

Methods: A retrospective study (n = 166) was performed. MRD was determined using multiparameter flow cytometry.

Validation of a Chinese version critical-care pain observation tool in nonintubated and intubated critically ill patients: Two cross-sectional studies.

Aims And Objectives: To validate the Chinese version of the Critical-Care Pain Observation Tool (CPOT) in nonintubated and intubated ICU patients.

Background: While CPOT was found to have the best psychometric properties among objective pain assessment scales, there is no Chinese version CPOT for nonintubated patients.

Design: Cross-sectional design was used in these two observational studies.

New approaches in allogenic transplantation in AML.

Acute myeloid leukemia (AML) is a heterogeneous disorder with high morbidity and mortality. Allogeneic stem cell transplantation (allo-SCT) is an effective, and sometimes the only, curative postremission therapy for AML patients. Based on genetic risk classification, the published data have suggested that allo-SCT be recommended for high- and most intermediate-risk AML but not for low-risk AML in first complete remission (CR1).

Minimal residual disease status determined by multiparametric flow cytometry pretransplantation predicts the outcome of patients with ALL receiving unmanipulated haploidentical allografts.

This study evaluated the effects of pretransplantation minimal residual disease (pre-MRD) on outcomes of patients with acute lymphoblastic leukemia (ALL) who underwent unmanipulated haploidentical stem cell transplantation (haplo-SCT). A retrospective study including 543 patients with ALL was performed. MRD was determined using multiparametric flow cytometry.

Strategies for Enhancing and Preserving Anti-leukemia Effects Without Aggravating Graft-Versus-Host Disease.

Allogeneic stem cell transplantation (allo-SCT) is a curable method for the treatment of hematological malignancies. In the past two decades, the establishment of haploidentical transplant modalities make "everyone has a donor" become a reality. However, graft-versus-host disease (GVHD) and relapse remain the major two causes of death either in the human leukocyte antigen (HLA)-matched transplant or haploidentical transplant settings, both of which restrict the improvement of transplant outcomes.

Patterns of Use of Docetaxel-Containing Adjuvant Chemotherapy Among Chinese Patients with Operable Breast Cancer: A Multicenter Observational Study.

Introduction: Adjuvant docetaxel-based chemotherapy is frequently used in the treatment of operable early breast cancer (EBC). This study investigated patterns of docetaxel use in patients with EBC in real-world clinical practice in China.

Methods: This was a multicenter, prospective, observational study of Chinese women with operable breast cancer in tier 1 non-oncology-specific hospitals and other city hospitals in China.

Effects of Low-Dose Glucocorticoid Prophylaxis on Chronic Graft-versus-Host Disease and Graft-versus-Host Disease-Free, Relapse-Free Survival after Haploidentical Transplantation: Long-Term Follow-Up of a Controlled, Randomized Open-Label Trial.

This long-term follow-up study evaluated the effects of corticosteroid prophylaxis on graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) based on a controlled open-label randomized trial in which 228 allotransplant recipients were categorized as low risk (n = 83, group A) or high risk; patients at high risk were randomly assigned to receive (n = 72, group B) or not receive (n = 73, group C) low-dose methylprednisolone prophylaxis. The cumulative incidences of chronic GVHD, relapse, nonrelapse mortality, leukemia-free survival, overall survival, and GRFS were 60%, 19%, 16%, 68%, 73%, and 46%, respectively, in all cases. Compared with the patients in group C, the cases in group B experienced a lower cumulative incidence of moderate to severe chronic GVHD (42% versus 20%; P = .

Quantity and Quality Reconstitution of NKG2A Natural Killer Cells Are Associated with Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation.

The immune mechanism underlying graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (HSCT) remains unclear. Natural killer (NK) cells play a crucial role in mediating pathogen-specific immunity and are the first donor-derived lymphocytes reconstituted post-HSCT. However, NK cells vary at different stages after HSCT.

The significance of peri-transplantation minimal residual disease assessed by multiparameter flow cytometry on outcomes for adult AML patients receiving haploidentical allografts.

A retrospective study (n = 460) was performed to assess the relationship between minimal residual disease (MRD) and transplant outcomes in a haplo-stem cell transplantation (SCT) setting. Patients from the pre-MRDneg group and the pre-MRDpos group had comparable outcomes. Compared to post-MRDneg patients, post-MRDpos patients had a higher incidence of relapse (100.

Reversal of T Cell Exhaustion by the First Donor Lymphocyte Infusion Is Associated with the Persistently Effective Antileukemic Responses in Patients with Relapsed AML after Allo-HSCT.

Donor lymphocyte infusion (DLI) is an effective approach to treat acute myelogenous leukemia (AML) relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) that significantly improves the survival of relapsed patients. However, the mechanism of an effective antileukemic response following DLI in AML relapse remains elusive. Here, we investigated the role of T cell exhaustion in AML relapse after allo-HSCT in prospective cohorts of 41 patients with the first AML relapse and 41 nonrelapsed AML control subjects after allo-HSCT and determined whether DLI exerts effective antileukemic effects by reversing T cell exhaustion in the relapsed cohorts by detecting the phenotypes and functions of T cells using flow cytometry.

Predicted indirectly recognizable HLA epitopes are not associated with clinical outcomes after haploidentical hematopoietic stem cell transplantation.

Haploidentical stem cell transplantation (haplo-SCT) provides an alternative method to cure patients with malignant and nonmalignant hematologic diseases who lack a human leukocyte antigen (HLA) matched related or unrelated donor. HLA disparity between donor and patient was the main reason causing lots of clinical immune response. The aim of this study was to investigate whether indirect recognition of mismatched HLA could predict the clinical outcomes in haplo-SCT.

Development of magnesium-based biodegradable metals with dietary trace element germanium as orthopaedic implant applications.

Unlabelled: From the perspective of element biosafety and dietetics, the ideal alloying elements for magnesium should be those which are essential to or naturally presented in human body. Element germanium is a unique metalloid in the carbon group, chemically similar to its group neighbors, Si and Sn. It is a dietary trace element that naturally presents in human body.

Platelet transfusion refractoriness after T-cell-replete haploidentical transplantation is associated with inferior clinical outcomes.

Haploidentical stem cell transplantation (haplo-SCT) has been an alternative source of bone marrow for patients without human leukocyte antigen (HLA)-matched donors. The aim of this study was to investigate the relationships between platelet transfusion refractoriness (PTR) and clinical outcomes in the setting of haplo-SCT. Between May 2012 and March 2014, 345 patients who underwent unmanipulated haplo-SCT were retrospectively enrolled.

Comparison of reference values for immune recovery between event-free patients receiving haploidentical allografts and those receiving human leukocyte antigen-matched sibling donor allografts.

To establish optimal reference values for recovered immune cell subsets, we prospectively investigated post-transplant immune reconstitution (IR) in 144 patients who received allogeneic stem cell transplantation (allo- SCT) and without showing any of the following events: poor graft function, grades II‒IV acute graft-versus-host disease (GVHD), serious chronic GVHD, serious bacterial infection, invasive fungal infection, or relapse or death in the first year after transplantation. IR was rapid in monocytes, intermediate in lymphocytes, CD3 Tcells, CD8 T cells, and CD19 B cells, and very slow in CD4 T cells in the entire patient cohort. Immune recovery was generally faster under HLA-matched sibling donor transplantation than under haploidentical transplantation.

Immune reconstitution in patients with acquired severe aplastic anemia after haploidentical stem cell transplantation.

Immune recovery (IR) after haploidentical stem cell transplantation (haplo-SCT) in severe aplastic anemia (SAA) patients remains relatively unknown. In this study, we examined immune cell subset counts and immunoglobulins in 81 SAA patients from day 30 to day 365 after haplo-SCT. Simultaneously, we determined which factors influence IR and analyzed the effects of immune cell subsets on transplant outcomes.

Haploidentical allograft is superior to matched sibling donor allograft in eradicating pre-transplantation minimal residual disease of AML patients as determined by multiparameter flow cytometry: a retrospective and prospective analysis.

Background: This study compared the effects of pre-transplantation minimal residual disease (pre-MRD) on outcomes in AML patients who underwent human leukocyte antigen-matched sibling donor transplantation (MSDT) or who received unmanipulated haploidentical allografts.

Methods: A retrospective study (n = 339) and a prospective study (n = 340) were performed. MRD was determined using multiparameter flow cytometry.

The Different Dynamic Changes of Nerve Growth Factor in the Dorsal Horn and Dorsal Root Ganglion Leads to Hyperalgesia and Allodynia in Diabetic Neuropathic Pain.

Background: Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes and more than half of the patients with DPN have self-reported symptoms referring to painful diabetic neuropathy (PDN). Nerve growth factor (NGF) is a key factor for the nervous system, but the role of it in the neuropathic pain of diabetic patients is unclear.

Objective: This study aimed to investigate the relationship between the dynamic expression of NGF in dorsal horn and dorsal root ganglion (DRG) of diabetic rats and hyperalgesia and allodynia in diabetic neuropathic pain.