With the increasing incidence of kidney diseases, there is an urgent need to develop therapeutic strategies to combat post-injury fibrosis. Immune cells, including platelets, play a pivotal role in this repair process, primarily through their released cytokines. However, the specific role of platelets in kidney injury and subsequent repair remains underexplored. Here, the detrimental role of platelets in renal recovery following ischemia/reperfusion injury and its contribution to acute kidney injury  to chronic kidney disease transition is aimed to investigated. In this study, it is shown that depleting platelets accelerates injury resolution and significantly reduces fibrosis. Employing advanced single-cell and spatial transcriptomic techniques, macrophages as the primary mediators modulated by platelet signals is identified. A novel subset of macrophages, termed "cycling M2", which exhibit an M2 phenotype combined with enhanced proliferative activity is uncovered. This subset emerges in the injured kidney during the resolution phase and is modulated by platelet-derived thrombospondin 1 (THBS1) signaling, acquiring profibrotic characteristics. Conversely, targeted inhibition of THBS1 markedly downregulates the cycling M2 macrophage, thereby mitigating fibrotic progression. Overall, this findings highlight the adverse role of platelet THBS1-boosted cycling M2 macrophages in renal injury repair and suggest platelet THBS1 as a promising therapeutic target for alleviating inflammation and kidney fibrosis.

Ferroptosis is an iron-dependent programmed cell death associated with severe kidney diseases, linked to decreased glutathione peroxidase 4 (GPX4). However, the spatial distribution of renal GPX4-mediated ferroptosis and the molecular events causing GPX4 reduction during ischemia-reperfusion (I/R) remain largely unknown. Using spatial transcriptomics, we identify that GPX4 is situated at the interface of the inner cortex and outer medulla, a hyperactive ferroptosis site post-I/R injury. We further discover OTU deubiquitinase 5 (OTUD5) as a GPX4-binding protein that confers ferroptosis resistance by stabilizing GPX4. During I/R, ferroptosis is induced by mTORC1-mediated autophagy, causing OTUD5 degradation and subsequent GPX4 decay. Functionally, OTUD5 deletion intensifies renal tubular cell ferroptosis and exacerbates acute kidney injury, while AAV-mediated OTUD5 delivery mitigates ferroptosis and promotes renal function recovery from I/R injury. Overall, this study highlights a new autophagy-dependent ferroptosis module: hypoxia/ischemia-induced OTUD5 autophagy triggers GPX4 degradation, offering a potential therapeutic avenue for I/R-related kidney diseases.

We aimed to determine the relationship between lymphocyte subsets on day 30 (D30) and prognosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. We retrospectively examined the clinical outcomes and lymphocyte subsets on D30 after allo-HSCT in 115 pediatric patients at the Children's Hospital of Soochow University between January 2016 and June 2019. Measurements were performed using flow cytometry on D30. Lymphocyte subsets were compared among the umbilical cord blood (UCB) (n = 22), HLA-matched sibling donor (MSD) (n = 14), haploidentical donor transplantation (HID) (n = 57), and unrelated donor transplantation (UD) (n = 22) groups. The relationships between the frequencies and counts of lymphocyte subsets and clinical outcomes were analyzed. T and B cell counts were the highest in the MSD group compared to the other groups, and natural killer cell counts were the highest in the UCB group. Lymphocyte subsets on D30 after allo-HSCT were correlated with the occurrence of acute (aGVHD) and chronic graft versus host disease (cGVHD). A high frequency of B cells (≥4.65%) was associated with the development of severe aGVHD. High frequencies of CD4+T (≥10.25%) were correlated with extensive cGVHD. Moreover, a high frequency of CD4+T cells (≥9.80%) was correlated with GVHD-free and failure-free survival (GFFS) after allo-HSCT. However, on D30, there were no statistically significant correlations between viral infections and lymphocyte subsets. The frequencies of lymphocyte subsets on D30 after allo-HSCT are good indicators of prognosis after allo-HSCT in children.

Background: Hemorrhagic cystitis (HC) is a severe complication of allo-HSCT, characterized by irritative symptoms of the urinary tract and a higher morbidity rate. The risk factors and prognosis of HC are still unclear. Objective: The objective of this study is to identify risk factors and outcomes to improve treatment in pediatric SAA patients undergoing HSCTs in the Children's Hospital of Soochow University. Methods: A total of 97 SAA patients as a cohort were enrolled from 2010 to 2019 in the Children's Hospital of Soochow University and a number of factors related to HC and outcomes were analysed. In all transplants (except UCBT), patients received a combination of G-CSF stimulated bone marrow (BM) and peripheral blood stem cell (PBSC). The minimum number of CD34 + cells is 5 x 10(6) cells/kg. Results: Mononuclear cells dose (MNC, cut off: 8.53 x 10(8)/kg) and grade II-1V acute graft versus host disease (aGVHD) were identified as independent risk factors for HC. Patients without HC had better overall survival (OS) than with HC (No HC: 98.6%+/- 1.4% vs HC: 87.4% +/- 6.8%, p = 0.03). Conclusion: We concluded that aGVHD and MNC dose in graft might play an important role in the development of HC in pediatric SAA patients undergoing allo-HSCT. HC is also a key complication affecting the prognosis of children with SAA after alto-HSCT.

Abstract Objective and Purpose: Despite improvements in medical management, both engraftment syndrome (ES) and pre-engraftment syndrome (pre-ES) which were named as peri-engraftment (peri-ES)remain associated with severe morbidity and decreased the survival following hematopoietic stem cell transplantation (HSCT). Though many studies on peri-EShave been published in recent years, there is no report on the incidence of peri-ES and related factors in pediatric HSCT, Meanwhile, the intervention with MP on peri-ES remains controvertial. Methods and patients: We retrospectively analyzed the data of 34 cases of pediatric allo-HSCT patients and the effect of methylprednisolone (MP) on the outcome of children with peri-ES transplanted between Nov 2010 and Dec 2013. The stem cell sources came from bone marrow alone [n=7], combining with peripheral blood [n=10], and cord blood alone [n=10], combining with bone marrow anf peripheral blood (n=7). Clinical characteristics and HSCT type were illustrated in Table 1 and 2. The incidence rate of peri-ES in cord blood transplantation (CBT), haploid transplants and sibling matched donor were 88.24%, 87.570% and 11.11%, respectively. All patients, who received either CBT or Hapolidentical SCT in conjunction of cord blood as the third part donor,developed peri-ES. We also identified that the peri-ES was highly associated with HLA disparity and mismatched ABO and aGvHD (Table 3 and 4).The median time of onset of peri-ES was 9 days after allo-HSCT. The most common symptoms of the peri-ES was eruthrodermous rash, followed by fever (Table 5). Twenty three children with peri-HSCT received intravenous MP at three doses of 0.5mg/kg, 1mg/kg, and 2mg/kg, respectively, based on the organs involved and the severity of peri-ES (Table 6). An excellent outcome was observed with relieving peri-ES in every patientand without influencingthe outcome of acute graft versus host disease (aGvHD), chronicgraft versus host disease (cGvHD), cytomegalovirus (CMV) infection, relapse, and overall survival (OS) with median follow up of xx months. (Table 4 and Figure 1 and 2). Conclusion: Peri-ES is closely associated with the stem cell source with the sequence of CB, PB and BM. Meanwhile, disparity of HLA type and blood type mismatch also contributed to peri-ES. peri-ES caneasily proceeded into aGvHD. MP efficiently relieved the process of peri-ES without any significant adverse event or affecting theoutcome of HSCT and can be recommended to control peri-ES in this patient population.Table 1.The clinical and laboratory characteristics of HSCT patientsViable NumberAge (year)Median, range9(1-16)SexMale/female20/14Primary diseaseAcute myeloid leukemia17Acute lymphoblastic leukemia4Chronic myelogenous leukemia2Aplastic anemia8Myelodysplastic syndrome (monosome 7)1Juvenile myelomonocytic leukemia2Number of infused nuclear cellsCB Median (range), 107/kg4.8(1.2-9.6)Haplo Median (range), 108/kg10.65(7.2-14.39)Sibling Median (range), 108/kg9.6(6.48-18.66)Number of infused CD34+ cellsCB Median (range), 106/kg0.32(0.047-0.52)Haplo Median (range), 106/kg4.6(1.92-8.36)Sibling Median (range), 106/kg4.4(2.5-8.37)HLA matching(low resolution) of A, B, DR6/6(sibling or CBT)175/6(Haplo or CBT)74/6(Haplo or CBT)63/6(Haplo or CBT)4Table 2.Risk factors for peri-ESRisk factorsperi-ES group(n=23 )Non peri-ES group (n= 11)Totalperi-ES /Total(%) SourceBM0440BM+PB15616.67BM+PB+CB707100CB1521788.24 Transplantation typesibling18911.11unrelated1521788.24Haploid71887.50 sexMale1282060.00Female1131478.57 ABO compatibilitymatched991850.00mismatched1421687.50 HLA disparitymatched891747.06mismatched1521788.24Neutrophilengraftmentmedian+14+13.5STR(2W)median96.8%95.7%Table 3.The Effect of MP on HSCT complicationsOutcome 0.5mg/kg1mg/kg2mg/kgNon peri-ESP 1P 2Neutrophil engraftment(median day)+16+15+13.513.50.5320.478aGVHD4/85/76/82/110.5290.010cGVHD1/82/72/82/110.7251.000CMV infection4/85/76/87/110.5291.000Relapse1/80/70/82/110.4980.239 BM, bone marrow; CB, cord blood; PB, peripheral blood; HLA, human leukocyte antigen; STR on second week. Note: P1: the comparison among three different doses of MP; P2: A comparison between peri-ES group and non-peri-ES group. Figure 1 Overall survival of pediatric allo-HSCT with and without peri-ES Figure 1. Overall survival of pediatric allo-HSCT with and without peri-ES Disclosures No relevant conflicts of interest to declare.