Objective:To investigate the impact of donor human leukocyte antigen (HLA) -Bw4 expression on natural killer (NK) cell reconstitution and transplant outcomes in recipients undergoing haploidentical hematopoietic stem cell transplantation (HSCT) from maternal or related donors without ex vivo T-cell depletion.Methods:This study prospectively enrolled 32 patients who received T-replete haploidentical HSCT from maternal or collateral donors (cohort 1) to evaluate the facilitating effect of donor HLA-Bw4 expression on NK cell reconstitution. Furthermore, a retrospective analysis was conducted on 278 patients who underwent T-replete haploidentical HSCT from maternal or collateral donors (cohort 2) to analyze the impact of donor HLA-Bw4 expression on HSCT outcomes. Thus, a comparison was made between the effects of donor HLA-Bw4 expression on HSCT outcomes in patients receiving or not receiving post-transplant cyclophosphamide (PT-Cy) conditioning.Results:Donors expressing HLA-Bw4 alleles facilitated NK cell reconstitution and functional recovery, which remained unaffected by PT-Cy. Donors with HLA-Bw4 expression were associated with reduced transplant-related mortality (TRM), particularly mortality related to infections. The use of PT-Cy did not impact the ability of donor HLA-Bw4 to decrease TRM.Conclusion:In haploidentical HSCT from maternal or related donors without ex vivo T-cell depletion, the presence of donor HLA-Bw4 expression promotes rapid NK cell reconstitution and functional recovery and is significantly associated with lower TRM, especially infection-related mortality. These findings underscore the clinical significance of donor HLA-Bw4 expression in patients who underwent HSCT. Hence, the consideration of donor HLA-Bw4 in recipient selection and HSCT strategies holds important clinical implications.

BACKGROUND:In recent years,with the development of biological scaffold materials and bioprinting technology,tissue-engineered bone has become a research hotspot in bone defect repair. OBJECTIVE:To summarize the current treatment methods for bone defects,summarize the biomaterials and bioprinting technology for preparing tissue-engineered bone scaffolds,and explore the application of biomaterials and printing technology in tissue engineering and the current challenges. METHODS:Search terms were"bone defect,tissue engineering,biomaterials,3D printing technology,4D printing technology,bioprinting,biological scaffold,bone repair"in Chinese and English.Relevant documents published from January 1,2009 to December 1,2022 were retrieved on CNKI,PubMed and Web of Science databases.After being screened by the first author,high-quality references were added.A total of 93 articles were included for review. RESULTS AND CONCLUSION:The main treatment methods for bone defects include bone transplantation,membrane-guided regeneration,gene therapy,bone tissue engineering,etc.The best treatment method is still uncertain.Bone tissue engineering technology is a new technology for the treatment of bone defects.It has become the focus of current research by constructing three-dimensional structures that can promote the proliferation and differentiation of osteoblasts and enhance the ability of bone formation.Biological scaffold materials are diverse,with their characteristics,advantages and disadvantages.A single biological material cannot meet the demand for tissue-engineered bone for the scaffold.Usually,multiple materials are combined to complement each other,which is to meet the demand for mechanical properties while taking into account the biological properties of the scaffold.Bioprinting technology can adjust the pore of the scaffold,build a complex spatial structure,and is more conducive to cell adhesion,proliferation and differentiation.The emerging 4D printing technology introduces"time"as the fourth dimension to make the prepared scaffold dynamic.With the synchronous development of smart materials,4D printing technology provides the possibility of efficient repair of bone defects in the future.

Chimeric antigen receptor (CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia (ALL). Measurable/minimal residual disease (MRD) monitoring plays a significant role in the prognostication and management of patients undergoing CAR-T-cell therapy. Common MRD detection methods include flow cytometry (FCM), polymerase chain reaction (PCR), and next-generation sequencing (NGS), and each method has advantages and limitations. It has been well documented that MRD positivity predicts a poor prognosis and even disease relapse. Thus, how to perform prognostic evaluations, stratify risk based on MRD status, and apply MRD monitoring to guide individual therapeutic decisions have important implications in clinical practice. This review assesses the common and novel MRD assessment methods. In addition, we emphasize the critical role of MRD as a prognostic biomarker and summarize the latest studies regarding MRD-directed combination therapy with CAR-T-cell therapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT), as well as other therapeutic strategies to improve treatment effect. Furthermore, this review discusses current challenges and strategies for MRD detection in the setting of disease relapse after targeted therapy.

Humans ; Receptors, Chimeric Antigen ; T-Lymphocytes ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Prognosis ; Immunotherapy, Adoptive ; Hematopoietic Stem Cell Transplantation ; Receptors, Antigen, T-Cell ; Recurrence

OBJECTIVE To systemically sort out the main practices of local drug online procurement， so as to provide reference for national and local governments to improve drug online procurement policies and drug price formation mechanism. METHODS By searching the official websites of 31 provincial medical security bureaus and drug-centralized procurement platforms in China， the classification methods and main goals of local drug online procurement were summarized， then the main practices of local drug online procurement were analyzed based on the main goals， and corresponding suggestion was put forward. RESULTS & CONCLUSIONS There were two classification methods of online drug procurement in each province， one is based on online or purchase methods， and the other is based on drug dimensions. Five main objectives of online drug procurement in each province are to ensure reasonable drug prices， meet clinical drug demand， ensure stable drug supply， cooperate with the implementation of drug policies， and standardize the behavior of transaction subjects. In order to achieve the five goals， each province has taken some targeted measures， but the severity of the policy varies greatly. In order to further improve the online drug procurement policy and improve the market-oriented online drug price formation mechanism， it is suggested to build the top-level design of online drug procurement， strengthen the management of the price comparison relationship of similar drugs， give full play to the monitoring function of the drug-centralized procurement platform and establish a national unified drug-centralized procurement platform.

Objective: To explore the effect of C1q / tumor necrosis factor-related protein 9 ( CTRP9 ) on the expression of genes and proteins related to lipid metabolism of brown adipose tissue (BAT) in mice after cold stimulation． Methods : C57BL /6J male mice were injected with adenovirus Ad-GFP (control group) or Ad-CTRP9 ( experience group) into the scapular region and kept for 7 days．After cold stimulation at 4 ℃ for 10 hours，the expression levels of BAT marker genes and proteins were detected by real time PCR and Western blot. Results: Overexpression of CTRP9 induced by cold stimulation significantly increased the mRNA level of iodothyronine deiodinase 2 (Dio2) in BAT (P＜0. 01) ．Additionally，there was no significant difference in the expression of BAT marker genes ( UCP-1，PGC-1 α , PRDM16 and ARβ3) ，and liposynthesis and lipolysis related genes (PPARγ , HSL and ATGL) ．Uncoupling protein 1 (UCP-1) protein expression was upregualted in Ad-CTRP9 compared to the Ad-GFP control group ，while the expression of lipolysis related protein adipose triglyceride lipase ( ATGL) decreased significantly (P＜0. 05) ． Conclusion In cold environment，overexpression of CTRP9 promotes the accumulation of UCP-1 protein in BAT，upregulates the expression of thyroid hormone signal related gene Dio2，and inhibits triglyceride hydrolysis to maintain a constant body temperature.

BACKGROUND: Recombinant human thrombopoietin (rh-TPO) and eltrombopag are two distinct TPO receptor agonists (TPO-RAs) with different mechanisms. During the pandemic, when immunosuppressive medications are controversial, switching to another TPO-RA may be worth exploring in patients who do not benefit from their first TPO-RA. We investigated the outcomes of switching from rh-TPO to eltrombopag or vice versa in immune thrombocytopenia (ITP) patients. METHODS: This prospective, open-label, observational investigation included 96 adult ITP patients who needed to switch between rh-TPO and eltrombopag between January 2020 and January 2021 at Peking University People's Hospital in China. The study evaluated response rates and platelet counts at different time points after the switch, bleeding events, time to response, duration of response, and adverse events. RESULTS: At 6 weeks after switching, response was observed in 21/49 patients (43%) who switched for inefficacy and 34/47 patients (72%) who switched for non-efficacy-related issues. In the inefficacy group, 9/27 patients (33%) responded to eltrombopag, and 12/22 patients (55%) responded to rh-TPO. In the non-efficacy-related group, 21/26 (81%) and 13/21 (62%) patients in the eltrombopag and rh-TPO groups maintained their response rates at 6 weeks after switching, respectively. Response at 6 months was achieved in 24/49 patients (49%) switching for inefficacy and 37/47 patients (79%) switching for non-efficacy issues. In the inefficacy group, 13/27 patients (48%) responded to eltrombopag, and 11/22 patients (50%) responded to rh-TPO. In the non-efficacy-related group, 22/26 patients (85%) and 15/21 patients (71%) in the eltrombopag and rh-TPO groups maintained their response rates at 6 months after switching, respectively. Both eltrombopag and rh-TPO were well tolerated. CONCLUSIONS: Our study confirmed the safety and effectiveness of switching between rh-TPO and eltrombopag for ITP patients who had no response to or experienced adverse events with their first TPO-RA. When the switch was motivated by other reasons, including patient preference and platelet count fluctuations, the probability of response was high. REGISTRATION ClinicalTrials.gov, NCT04214951.
Adult ; Humans ; Purpura, Thrombocytopenic, Idiopathic ; Thrombopoietin/adverse effects* ; Prospective Studies ; Recombinant Fusion Proteins ; Receptors, Fc/therapeutic use* ; Receptors, Thrombopoietin/therapeutic use* ; Thrombocytopenia/chemically induced* ; Benzoates/adverse effects* ; Hydrazines/adverse effects*

Chimeric antigen receptor(CAR)-T cell immunotherapy for refractory and relapsed acute lymphoblastic leukemia (R/R ALL) is one of the breakthroughs in the field of hematological malignant disease treatment. However, several challenges remain, such as immune rejection of allogeneic CAR-T cells, leukemia relapse, as well as could we apply CAR-T cell immunotherapy to ALL patients with positive measurable residual disease and those of newly diagnosed cases. The safety and efficiency of CAR-T therapy will be further improved for patients with ALL only by establishing appropriate strategies to address these challenges.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the main curable therapies for patients with acute lymphoblastic leukemia (ALL). This article discusses the status of allo-HSCT for ALL as well as how to combine targeted therapy with allo-HSCT to improve outcomes of ALL in the era of targeted therapy based on the data obtained from the 63rd American Society of Hematology (ASH) Annual Meeting.

Mood disorders and substance use disorders often co-occur,but few evidence-based data have been conducted to guide the management of comorbidity bipolar disorder with alcohol use disorder. Therefore,it's lack of clinical researches and expert consensus. This review inducted the research progress of the comorbidities of bipolar disorder and alcohol use disorder in recent years,and finds that drug treatment or combined treatment with other treatment methods has certain curative effect suggesting that the comprehen-sive treatment of drug or combined non-drug treatment for comorbidities is the future direction.