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Background: Pyruvate kinase deficiency (PKD) is an autosomal recessive disorder caused by a PK‐LR gene mutation. Allogeneic hematopoietic cell transplantation (HCT) is an effective cure for PKD. However, the experience of applying HCT in PKD is limited. Methods: We present a child with novel PK‐LR gene mutations who was successfully cured by matched unrelated donor peripheral blood stem cell transplantation (MUD‐PBSCT). Results: A 4‐year‐old, male patient suffered severe hemolytic anemia and jaundice 5 h after birth. Gene sequencing showed that the pyruvate kinase‐liver and RBC (PK‐LR) gene had a nonsense mutation in exon 5: c.602G>A (p.W201X), and large deletions in exons 3–9. Both of them were novel pathogenic mutations of the PK‐LR gene. After transplantation, the hemoglobin level became normal and the nonsense mutation was undetectable. Grade Ⅳ acute graft‐versus‐host disease (aGVHD) and extensive chronic graft‐versus‐host disease (cGVHD) occurred in the patient. However, the GVHD was controlled effectively. The patient is alive and has good quality of life 22 months post‐transplant, but has mild oral lichen planus‐like lesion. Conclusion: Gene sequencing contributes to the diagnosis of PKD. HCT is an effective method for curing PKD, but we should explore how to reduce severe GVHD. [ABSTRACT FROM AUTHOR]

Background: Umbilical cord blood transplantation (UCBT) from unrelated donors is one of the successful treatments for acute leukemia in childhood. The most frequent side effect of UCBT is peri-engraftment syndrome (PES), which is directly associated with the greater prevalence of acute and chronic graft-versus-host-disease (aGvHD and cGvHD). In haploidentical stem cell transplantation, posttransplant cyclophosphamide (PTCY) has been demonstrated to be an effective method against GvHD. However, the effects of PTCY as a GvHD prophylactic in UCBT had not been investigated. This study aimed to evaluate the effects of PTCY on the outcomes of UCBT for pediatric acute leukemia.Methods: This retrospective study included 52 children with acute leukemia who underwent unrelated single-unit UCBT after myeloablative conditioning regimens. The results from the PTCY and non-PTCY groups were compared.Results: The incidence of transplantation-related mortality in non-PTCY and PTCY were 5% and 10% (p = 0.525), respectively. The incidence of relapse in non-PTCY and PTCY were 5% and 23% (p = 0.095), respectively. Second complete remission status (CR2) was an independent risk factor for relapse-free survival (hazard ratio = 9.782, p = 0.001). The odds ratio for sepsis or bacteremia incidence was significantly greater in the PTCY group (9.524, p = 0.017). PTCY group had increased rates of cytomegalovirus activity and fungal infection. The incidence of PES, aGvHD, cGvHD, and hemorrhagic cystitis in the PTCY group was lower than that in the non-PTCY group, although it was not significantly different. Additionally, higher doses of PTCY (29 mg/kg and 40 mg/kg) were associated with lower incidences of aGvHD and severe GvHD (65% and 29%, respectively) than lower doses (93% and 57%, respectively). Engraftment time and graft failure incidence were similar across groups.Conclusion: The results support the safety and efficiency of PTCY as part of PES controlling and GvHD prophylaxis in single-unit UCBT for children with acute leukemia. A PTCY dosage of 29 mg/kg to 40 mg/kg appears to be more effective in GvHD prophylaxis for UCBT patients. [ABSTRACT FROM AUTHOR]

Background: Silicon (Si) can confer plant resistance to both abiotic and biotic stress. In the present study, the priming effect of Si on rice (Oryza sativa cv Nipponbare) against the root-knot nematode Meloidogyne graminicola and its histochemical and molecular impact on plant defense mechanisms were evaluated. Results: Si amendment significantly reduced nematodes in rice roots and delayed their development, while no obvious negative effect on giant cells was observed. Increased resistance in rice was correlated with higher transcript levels of defense-related genes (OsERF1, OsEIN2 and OsACS1) in the ethylene (ET) pathway. Si amendment significantly reduced nematode numbers in rice plants with enhanced ET signaling but had no effect in plants deficient in ET signaling, indicating that the priming effects of Si were dependent on the ET pathway. A higher deposition of callose and accumulation of phenolic compounds were observed in rice roots after nematode attack in Si-amended plants than in the controls. Conclusion: These findings indicate that the priming effect may partially depend on the production of phenolic compounds and hydrogen peroxide. Further research is required to model the ethylene signal transduction pathway that occurs in the Si-plant-nematode interaction system and gain a better understanding of Si-induced defense in rice. [ABSTRACT FROM AUTHOR]

Background: Early‐onset mixed chimerism (MC) with a high proportion of residual host cells is considered a signal of graft rejection in patients undergoing allogenic hematopoietic stem cell transplantation for transfusion‐dependent thalassemia. In order to prevent graft rejection and minimize the risk of treatment‐related graft‐versus‐host disease (GVHD), we established a hierarchical management system based on chimerism analysis. Method: This retrospective study provides a comprehensive review of the characteristics, interventions, and outcomes of the 38 patients who developed MC after transplantation among the 144 pediatric thalassemia patients between July 2007 and January 2019 at our center. Results: A sibling donor, a blood type‐matched donor, conditioning regimens without fludarabine, and transplants containing <10 × 108 total nucleated cells/kg were identified to be associated with the development of MC. Among the 38 patients developing MC, only four patients rejected the grafts. The response rate to donor lymphocyte infusion (DLI, only for patients receiving sibling donor transplantation) and cytokine immunomodulation without DLI was 70.6% and 42.9%, respectively. Patients that developed GVHD after DLI or cytokine therapy had a more significant increase in donor cell chimerism (16%, range 0%‐35%) than those without (8.5%, range −21% to 40%, P =.049). However, even when treatment‐related GVHD was included, patients with MC had a lower cumulative incidence of total acute GVHD than patients with complete donor chimerism (29.2% vs 48.0%, P =.030). Conclusions: Interventions based on chimerism analysis were effective in preventing graft rejection and did not increase treatment‐related GVHD in thalassemia patients with MC. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma (GBM) with distant extension is rarely reported. We retrieved the data of GBM patients from the SEER database to identify the prognostic factors of GBM with distant extension and constructed a nomogram to predict the overall survival (OS) of these patients. Methods: The data of GBM patients between 2003 and 2018 were retrieved from the SEER Database. 181 GBM patients with distant extension were randomly divided into the training cohort (n = 129) and the validation cohort (n = 52) at a ratio of 7:3. The prognostic factors associated with the OS of the GBM patients were identified through univariate and multivariate cox analyses. A nomogram was constructed based on the training cohort to predict OS, and its clinical value was verified using the validation cohort data. Results: Kaplan–Meier curves showed that the prognosis was significantly worse for GBM patients with distant extension than GBM patients without distant extension. Stage (GBM patients with distant extension) was independent prognostic factor of survival. Multivariate Cox analyses demonstrated that age, surgery, radiotherapy and chemotherapy were independent risk factors for OS of GBM patients presenting with distant extension. The C-indexes of the nomogram for predicting OS were 0.755 (95% CI 0.713–0.797) and 0.757 (95% CI 0.703–0.811) for the training and validation cohorts, respectively. The calibration curves of both cohorts showed good consistency. The area under the curve (AUC) for predicting 0.25-year, 0.5-year and 1-year OS in the training cohort were 0.793, 0.864 and 0.867, respectively, and that in the validation cohort were 0.845, 0.828 and 0.803, respectively. The decision curve analysis (DCA) curves showed that the model to predict the 0.25-year, 0.5-year and 1-year OS probabilities was good. Conclusion: Stage (GBM patients with distant extension) is independent prognostic factor for GBM patients. Age, surgery, radiotherapy and chemotherapy are independent prognostic factors for GBM patients presenting with distant extension, and the nomogram based on these factors can accurately predict the 0.25-year, 0.5-year and 1-year OS of these patients. [ABSTRACT FROM AUTHOR]

The root-knot nematode Meloidogyne incognita causes severe damage to continuously cropping vegetables. The control of this nematode relies heavily on organophosphate nematicides in China. Here, we described resistance to the organophosphate nematicide fosthiazate in a greenhouse-collected resistant population (RP) and a laboratory susceptible population (SP) of M. incognita. Fosthiazate was 2.74-fold less toxic to nematodes from RP than that from SP. Quantitative real-time PCR revealed that the acetylcholinesterase2 (ace2) transcription level in the RP was significantly higher than that in the SP. Eighteen nonsynonymous amino acid differences in ace2 were observed between the cDNA fragments of the RP and SP. The acetylcholinesterase (AChE) protein activity in the RP was significantly reduced compared with that in the SP. After knocking down the ace2 gene, the ace2 transcription level was significantly decreased, but no negative impact on the infection of juveniles was observed. The 50% lethal concentration of the RNAi RP population decreased 40%, but the inhibition rate of fosthiazate against AChE activity was significantly increased in RP population. Thus, the increased fosthiazate insensitivity in the M. incognita resistant population was strongly associated with mutations in ace2. These results provide valuable insights into the resistance mechanism of root-knot nematode to organophosphate nematicides. [ABSTRACT FROM AUTHOR]