Mini-dose methotrexate combined with methylprednisolone for the initial treatment of acute GVHD: a multicentre, randomized trial.

BACKGROUND: There is an urgent unmet need for effective initial treatment for acute graft-versus-host disease (aGVHD) adding to the standard first-line therapy with corticosteroids after allogeneic haematopoietic stem cell transplantation (allo-HSCT). METHODS: We performed a multicentre, open-label, randomized, phase 3 study. Eligible patients (aged 15 years or older, had received allo-HSCT for a haematological malignancy, developed aGVHD, and received no previous therapies for aGVHD) were randomly assigned (1:1) to receive either 5 mg/m2 MTX on Days 1, 3, or 8 and then combined with corticosteroids or corticosteroids alone weekly. RESULTS: The primary endpoint was the overall response rate (ORR) on Day 10. A total of 157 patients were randomly assigned to receive either MTX plus corticosteroids (n = 78; MTX group) or corticosteroids alone (n = 79; control group). The Day 10 ORR was 97% for the MTX group and 81% for the control group (p = .005). Among patients with mild aGVHD, the Day 10 ORR was 100% for the MTX group and 86% for the control group (p = .001). The 1-year estimated failure-free survival was 69% for the MTX group and 41% for the control group (p = .002). There were no differences in treatment-related adverse events between the two groups. CONCLUSIONS: In conclusion, mini-dose MTX combined with corticosteroids can significantly improve the ORR in patients with aGVHD and is well tolerated, although it did not achieve the prespecified 20% improvement with the addition of MTX. TRIAL REGISTRATION: The trial was registered with clinicaltrials.gov (NCT04960644).

Salvage haploidentical transplantation for graft failure after first haploidentical allogeneic stem cell transplantation: an updated experience.

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. However, there are no recommended regimens for second transplantations for graft failure, especially in the haploidentical transplant setting. We recently reported encouraging outcomes using a novel method (haploidentical transplantation from a different donor after conditioning with fludarabine and cyclophosphamide). Herein, we report updated outcomes in 30 patients using this method. The median time of the second transplantation was 96.5 (33-215) days after the first transplantation. Except for one patient who died at +19d and before engraftment, neutrophil engraftments were achieved in all patients at 11 (8-24) days, while platelet engraftments were achieved in 22 (75.8%) patients at 17.5 (9-140) days. The 1-year OS and DFS were 60% and 53.3%, and CIR and TRM was 6.7% and 33.3%, respectively. Compared with the historical group, neutrophil engraftment (100% versus 58.5%, p < 0.001) and platelet engraftment (75.8% versus 32.3%, p < 0.001) were better in the novel regimen group, and OS was also improved (60.0% versus 26.4%, p = 0.011). In conclusion, salvage haploidentical transplantation from a different donor using the novel regimen represents a promising option to rescue patients with graft failure after the first haploidentical transplantation.

Haplotype-resolved assembly of auto-polyploid genomes via combining Hi-C and gametic data.

Haplotype-resolved genome assembly plays a crucial role in understanding allele-specific functions. However, obtaining haplotype-resolved assembly for auto-polyploid genomes remains challenging. Existing methods can be classified into reference-based phasing, assembly-based phasing, and gamete binning. Nevertheless, there is a lack of cost-effective and efficient methods for haplotyping auto-polyploid genomes. In this study, we propose a novel phasing algorithm called PolyGH, which combines Hi-C and gametic data. We conducted experiments on tetraploid potato cultivars and divided the method into three steps. Firstly, gametic data was utilized to bin non-collapsed contigs, followed by merging adjacent fragments of the same type within the same contig. Secondly, accurate Hi-C signals related to differential genomic regions were acquired using unique k-mers. Finally, collapsed fragments were assigned to haplotigs based on combined Hi-C and gametic signals. Comparing PolyGH with Hi-C-based and gametic data-based methods, we found that PolyGH exhibited superior performance in haplotyping auto-polyploid genomes when integrating both data types. This approach has the potential to enhance haplotype-resolved assembly for auto-polyploid genomes.

CAR-T Therapy Followed by Hematopoietic Stem Cell Transplantation Can Improve Survival in Children Relapsed/Refractory Philadelphia Chromosome-positive B-cell Acute Lymphoblastic Leukemia.

BACKGROUND: Philadelphia chromosome (Ph)-positive B-cell acute lymphoblastic leukemia (ALL) has a high complete remission (CR) rate, but relapse and prolonged measurable residual disease remain serious problems. We sought to describe the CR rate measurable residual disease negative rate and address the results and safety of pediatric patients who underwent after receiving chimeric antigen receptor (CAR) specific for CD19 (CAR-19) followed by hematopoietic stem cell transplantation (HSCT) for the treatment of Ph-positive ALL. METHODS: A descriptive study was conducted at Peking University People's Hospital from September 2013 to January 2021. 13 patients with relapsed/refractory Ph-positive B-ALL who received CAR-T therapy followed by allo-HSCT were included. We concentrated on the overall patient survival and CR rate. RESULTS: The median time between CAR-T therapy and allo-HSCT was 58 days. Among all the patients, the CR rate was 100%, the flow cytometry negativity rate was 84.62%, and the BCR-ABL negativity rate was 53.85% at 1 month after CAR-T infusion. All the patients achieved a major molecular response in 6 months after HSCT. After a median follow-up of 45 months, the 3-year OS rate was 66.7%, and the 3-year DFS rate was 61.5%. The 3-year OS rate of patients with BCR-ABL-positive pre-HSCT was significantly lower than that in the BCR-ABL-negative group (40.0% vs. 85.7%, P=0.042). Also, the same trend was observed for the 3-year DFS rate but did not differ significantly (40.0% vs. 75.0%, P=0.233). CONCLUSIONS: CAR-T therapy followed by allo-HSCT can be a safe and effective treatment for Ph-positive B-ALL pediatric patients.

Deep-learning-based image super-resolution of an end-expandable optical fiber probe for application in esophageal cancer diagnostics.

Significance: Endoscopic screening for esophageal cancer (EC) may enable early cancer diagnosis and treatment. While optical microendoscopic technology has shown promise in improving specificity, the limited field of view (<1 mm) significantly reduces the ability to survey large areas efficiently in EC screening. Aim: To improve the efficiency of endoscopic screening, we propose a novel concept of end-expandable endoscopic optical fiber probe for larger field of visualization and for the first time evaluate a deep-learning-based image super-resolution (DL-SR) method to overcome the issue of limited sampling capability. Approach: To demonstrate feasibility of the end-expandable optical fiber probe, DL-SR was applied on simulated low-resolution microendoscopic images to generate super-resolved (SR) ones. Varying the degradation model of image data acquisition, we identified the optimal parameters for optical fiber probe prototyping. The proposed screening method was validated with a human pathology reading study. Results: For various degradation parameters considered, the DL-SR method demonstrated different levels of improvement of traditional measures of image quality. The endoscopists' interpretations of the SR images were comparable to those performed on the high-resolution ones. Conclusions: This work suggests avenues for development of DL-SR-enabled sparse image reconstruction to improve high-yield EC screening and similar clinical applications.

Decreasing the steroid rapidly may help to improve the clinical outcomes of patients with intestinal steroid-refractory acute graft-versus-host disease receiving basiliximab treatment.

Intestinal steroid refractory acute graft-versus-host disease (SR-aGVHD) is the major cause of mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective cohort study aimed to identify the relationship between different steroid decreasing velocity and therapeutic response in patients with intestinal SR-aGVHD receiving basiliximab treatment, and also aimed to propose a reasonable steroid decreasing regimen for these patients. The median time for steroid dose decreasing to the 50% of initial dose and decreasing to the low-dose steroid for patients achieving ORR was 5 days and 12 days, respectively, which was both shorter than patients without achieving ORR. The ORR, NRM and survival in rapid and medium steroid decreasing group were all better than slow group. The cumulative incidence of ORR at any time was 90.4%, 78.1% and 62.3%, respectively, in rapid, medium, and slow group. The cumulative incidence of NRM at 1 year after basiliximab treatment was 18.7% (95% CI 11.3%-26.1%), 22.8% (95% CI 14.2%-31.4%) and 32.8% (95% CI 24.1%-41.5%), respectively, in rapid, medium, and slow group. The probability of OS at 1 year after basiliximab treatment was 76.9% (95% CI 68.9%-84.9%), 72.7% (95% CI 63.7%-81.7%), and 62.3% (95% CI 53.5%-71.1%), respectively, in rapid, medium, and slow group. Hence, it was helpful to decrease steroid to the 50% of initial dose ≤ 5 days and to the low-dose steroid ≤ 12 days after basiliximab treatment for intestinal SR-aGVHD patients, which may also be the reasonable steroid decrease protocol for these patients.

Study on the Melt Rheological Characterization of Micro-Tube Gas-Assisted Extrusion Based on the Cross-Scale Viscoelastic Model.

In the micro-tube gas-assisted extrusion process, flow theories ignoring cross-scale viscoelastic variations fail to effectively characterize the rheological state of the melt. To investigate the impact of cross-scale viscoelastic variation on the quality of the micro-tube gas-assisted extrusion, a 3D multiphase flow extrusion model incorporating a double gas-assisted layer was developed. Subsequently, we modified the DCPP constitutive equations based on the cross-scale factor model. Both the traditional and gas-assisted extrusions were simulated under macroscale and cross-scale models using the Ansys Polyflow. Finally, using the established gas-assisted extrusion platform, extrusion experiments were conducted. The results indicate that, owing to the reduced melt viscosity under the cross-scale model, the deformation behavior of the melt is more pronounced than in the macroscale model. The cross-scale model's numerical results more closely match the experimental outcomes under the same parameters, thereby confirming the feasibility of the theoretical analysis and numerical simulation. Moreover, the predictive capability of the cross-scale model for the micro-tube gas-assisted extrusion is further validated through numerical and experimental analyses with varying parameters. It is demonstrated that the cross-scale viscoelastic variation is a critical factor that cannot be overlooked in the gas-assisted extrusion.

Haploidentical hematopoietic stem cell transplantation with busulfan, cyclophosphamide, and fludarabine conditioning for X-linked adrenal cerebral leukodystrophy.

OBJECTIVE: We investigated the safety and efficacy of haploidentical stem cell transplantation (SCT) in pediatric patients with X-linked adrenoleukodystrophy (ALD). METHODS: A retrospective analysis of transplantation data from 29 cases of ALD, treated between December 2014 and April 2022, was conducted. Neurologic function scores (NFS) were assessed. The conditioning regimen was busulfan 9.6 mg/kg, cyclophosphamide 200 mg/kg, and fludarabine 90 mg/m2 (BFC). Graft-versus-host disease prophylaxis consisted of anti-human thymocyte globulin, cyclosporine A, mycophenolate mofetil, and short course of methotrexate. RESULTS: Among the 29 cases, 14 cases (NFS = 0) were asymptomatic, and 15 (NFS ≥ 1) were symptomatic. The median age at SCT was 8 years (range: 4-16 years); the median follow-up time was 1058 days (range: 398-3092 days); 28 cases were father donors and 1 case was a grandfather donor. Hematopoietic reconstitution was successful in all patients, and all of them achieved complete donor chimerism at the time of engraftment. The leading cause of death was still primary disease progression (n = 4). Survival free of major functional disabilities was 100% in asymptomatic patients versus 66.67% in the symptomatic group (p = .018). CONCLUSION: BFC regimen used in haploidentical SCT was administered safely without major transplant-related complications even in symptomatic patients, and neurological symptoms were stabilized after SCT.

Allogeneic stem cell transplantation is still a highly curative therapy in adults with philadelphia chromosome-positive acute lymphoblastic leukaemia.

The application of tyrosine kinase inhibitors (TKIs) and novel immunotherapies has improved outcomes in patients with Ph + acute lymphoblastic leukaemia (ALL), and the issue of whether there is still a need for stem cell transplantation has become controversial. We performed a retrospective study to explore whether stem cell transplantation still held a place in patients with Ph + ALL if only imatinib and 2nd generation TKIs are available and affordable. A total of 292 patients were included. The median age was 38 years [range 14-64, IQR 28-48]. Patients receiving transplants (n = 216) had better rates of 4-year disease-free survival (DFS, 68% vs. 24%, P < .0001) and overall survival (OS, 72% vs. 47%, P < .0001) than those receiving continuous TKIs plus chemotherapy (TKI-chemo) (n = 76). In the multivariate analysis, male sex, WBC count ≥ 95 × 109/L and PLT count ≤ 154 × 109/L at diagnosis were significantly associated with poorer outcomes, and transplantation was significantly associated with favourable DFS and OS. In addition, the transplant outcomes were superior in any subgroup according to the number of risk variables. Furthermore, propensity score matching (PSM) analyses showed similar findings in the whole cohort and in age- and BCR-ABL1 level-based subgroups after the first or second consolidation. In conclusion, transplantation as a one-time procedure for adults with Ph + ALL patients remains important in countries lacking accessibility to third-generation TKIs or immunotherapies, regardless of the depth of the molecular response.

Hematologic health services and practical characteristics: report of a nationwide survey among Chinese hematologists.

BACKGROUND: In the past 40 years, China has experienced tremendous economic development, but the current situation of hematologists has rarely been reported. A landscape survey of human resources is essential for healthcare development and policy formulation in the future. METHODS: The Chinese Society of Hematology initiated a survey of Chinese hematologists in mainland China for evaluating demographic and practice characteristics. Respondents were anonymous, and there were no limitations regarding their age, sex, etc. RESULTS: Totally 2032 hematologists responded, with a median age bracket of 36-45 years. Respondents were well engaged into subspecialties, and 28.1% acquired doctorates of philosophy. Hematopoietic cell transplantation (HCT) centers have been established all over China. Higher-GDP regions reported more advantages, including bigger scale of transplant centers (P < 0.001), younger age structure (P = 0.039), better education qualifications (P = 0.001) and less turnover intentions (P = 0.004), despite of increased risk of medical disputes (P = 0.028). Although females accounted for 65.5% of hematologists, males were older (P < 0.001), and had more senior professional titles (P < 0.001), academic positions (P < 0.001), opportunities for continuing education (P < 0.001), and paper publishing in the recent two years (P = 0.001). For turnover intention, the higher GDP regions led to an independently reduced risk (HR = 0.673, 95%CI [0.482-0.940], P = 0.020), whereas medical disputes resulted in an increased the risk (HR = 2.037, 95%CI [1.513-2.743], P < 0.001). Considering the impact of the COVID-19 pandemic, majority of respondents believed that the decline in patient visits and delay in treatment was within 30%. 67.9% of respondents reported a decrease of the use of bone marrow as grafts but 18.8% reported an increase of cord blood units. 35.0% of the respondents switched their daily work to support the anti-epidemic medical activities. CONCLUSIONS: We concluded the discipline of hematology in China has flourished in recent years with a young workforce, while regional economic and gender disparities warrant further continuous optimization. Joint efforts against the impact of COVID-19 are needed in the post-pandemic era.

Extracellular matrix protein 1 (ECM1) is a potential biomarker in B cell acute lymphoblastic leukemia.

B cell acute lymphoblastic leukemia (ALL) is characterized by the highly heterogeneity of pathogenic genetic background, and there are still approximately 30-40% of patients without clear molecular markers. To identify the dysregulated genes in B cell ALL, we screened 30 newly diagnosed B cell ALL patients and 10 donors by gene expression profiling chip. We found that ECM1 transcription level was abnormally elevated in newly diagnosed B cell ALL and further verified in another 267 cases compared with donors (median, 124.57% vs. 7.14%, P < 0.001). ROC analysis showed that the area under the curve of ECM1 transcription level at diagnosis was 0.89 (P < 0.001). Patients with BCR::ABL1 and IKZF1 deletion show highest transcription level (210.78%) compared with KMT2A rearrangement (39.48%) and TCF3::PBX1 rearrangement ones (30.02%) (all P < 0.05). Also, the transcription level of ECM1 was highly correlated with the clinical course, as 20 consecutive follow-up cases indicated. The 5-year OS of patients (non-KMT2A and non-TCF3::PBX1 rearrangement) with high ECM1 transcription level was significantly worse than the lower ones (18.7% vs. 72.9%, P < 0.001) and high ECM1 transcription level was an independent risk factor for OS (HR = 5.77 [1.75-19.06], P = 0.004). After considering transplantation, high ECM1 transcription level was not an independent risk factor, although OS was still poor (low vs. high, 71.1% vs. 56.8%, P = 0.038). Our findings suggested that ECM1 may be a potential molecular marker for diagnosis, minimal residual disease (MRD) monitoring, and prognosis prediction of B cell ALL.Trial registration Trial Registration Registered in the Beijing Municipal Health Bureau Registration N 2007-1007 and in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940 and ChiCTR-OPC-14005546]; http://www.chictr.org.cn .

SET domain containing 2 promotes megakaryocyte polyploidization and platelet generation through methylation of α-tubulin.

BACKGROUND: Megakaryocytes (MKs) are polyploid cells responsible for producing ∼1011 platelets daily in humans. Unraveling the mechanisms regulating megakaryopoiesis holds the promise for the production of clinical-grade platelets from stem cells, overcoming significant current limitations in platelet transfusion medicine. Previous work identified that loss of the epigenetic regulator SET domain containing 2 (SETD2) was associated with an increased platelet count in mice. However, the role of SETD2 in megakaryopoiesis remains unknown. OBJECTIVES: Here, we examined how SETD2 regulated MK development and platelet production using complementary murine and human systems. METHODS: We manipulated the expression of SETD2 in multiple in vitro and ex vivo models to assess the ploidy of MKs and the function of platelets. RESULTS: The genetic ablation of Setd2 increased the number of high-ploidy bone marrow MKs. Peripheral platelet counts in Setd2 knockout mice were significantly increased ∼2-fold, and platelets exhibited normal size, morphology, and function. By knocking down and overexpressing SETD2 in ex vivo human cell systems, we demonstrated that SETD2 negatively regulated MK polyploidization by controlling methylation of α-tubulin, microtubule polymerization, and MK nuclear division. Small-molecule inactivation of SETD2 significantly increased the production of high-ploidy MKs and platelets from human-induced pluripotent stem cells and cord blood CD34+ cells. CONCLUSION: These findings identify a previously unrecognized role for SETD2 in regulating megakaryopoiesis and highlight the potential of targeting SETD2 to increase platelet production from human cells for transfusion practices.

Prediction model for EBV infection following HLA haploidentical matched hematopoietic stem cell transplantation.

AIMS: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for hematological malignancies. However, viral infections, particularly EBV infection, frequently occur following allo-HSCT and can result in multi-tissue and organ damage. Due to the lack of effective antiviral drugs, these infections can even progress to post-transplant lymphoproliferative disorders (PTLD), thereby impacting the prognosis. In light of this, our objective is to develop a prediction model for EBV infection following allo-HSCT. METHODS: A total of 466 patients who underwent haploidentical hematopoietic stem cell transplantation (haplo-HSCT) between September 2019 and December 2020 were included in this study. The patients were divided into a development cohort and a validation cohort based on the timing of their transplantation. Our aim was to develop and validate a grading scale using these cohorts to predict the risk of EBV infection within the first year after haplo-HSCT. Additionally, single-cell RNA sequencing (sc-RNAseq) data from the bone marrow of healthy donors were utilized to assess the impact of age on immune cells and viral infection. RESULTS: In the multivariate logistic regression model, four predictors were retained: donor age, female-to-male transplant, graft MNC (mononuclear cell) dose, and CD8 dose. Based on these predictors, an EBV reactivation predicting score system was constructed. The scoring system demonstrated good calibration in both the derivation and validation cohorts, as confirmed by the Hosmer-Lemeshow test (p > 0.05). The scoring system also exhibited favorable discriminative ability, as indicated by the C statistics of 0.72 in the derivation cohort and 0.60 in the validation cohort. Furthermore, the clinical efficacy of the scoring system was evaluated using Kaplan-Meier curves based on risk ratings. The results showed significant differences in EBV reactivation rates between different risk groups, with p-values less than 0.001 in both the derivation and validation cohorts, indicating robust clinical utility. The analysis of sc-RNAseq data from the bone marrow of healthy donors revealed that older age had a profound impact on the quantity and quality of immune subsets. Functional enrichment analysis highlighted that older age was associated with a higher risk of infection. Specifically, CD8 + T cells from older individuals showed enrichment in the pathway of "viral carcinogenesis", while older CD14 + monocytes exhibited enrichment in the pathway of "regulation of viral entry into host cell." These findings suggest that older age may contribute to an increased susceptibility to viral infections, as evidenced by the altered immune profiles observed in the sc-RNAseq data. CONCLUSION: Overall, these results demonstrate the development and validation of an effective scoring system for predicting EBV reactivation after haplo-HSCT, and provide insights into the impact of age on immune subsets and viral infection susceptibility based on sc-RNAseq analysis of healthy donors' bone marrow.

Targeting TYK2 alleviates Rab27A-induced malignant progression of non-small cell lung cancer via disrupting IFNα-TYK2-STAT-HSPA5 axis.

Rab27A is a small GTPase-mediating exosome secretion, which participates in tumorigenesis of multiple cancer types. Understanding the biological role of Rab27A in non-small cell lung cancer (NSCLC) is of great importance for oncological research and clinical treatment. In this study, we investigate the function and internal mechanism of Rab27A in NSCLC. Results show that Rab27A is overexpressed in NSCLC, and regulates the tumor proliferation, migration, invasion, and cell motility in vitro and in vivo, and is negatively regulated by miR-124. Further research reveals that upregulated Rab27A can induce the production of IFNα in the medium by mediating exosome secretion. Then IFNα activates TYK2/STAT/HSPA5 signaling to promote NSCLC cell proliferation and metastasis. This process can be suppressed by TYK2 inhibitor Cerdulatinib. These results suggest that Rab27A is involved in the pathogenesis of NSCLC by regulating exosome secretion and downstream signaling, and inhibitors targeting this axis may become a promising strategy in future clinical practice.

B cell pathway dual inhibition for systemic lupus erythematosus: a prospective single-arm cohort study of telitacicept.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease associated with B-cell hyperactivity. Telitacicept is a transmembrane activator, calcium modulator, and cyclophilin ligand interactor-Fc fusion protein, which can neutralize both B-cell lymphocyte stimulator and a proliferation-inducing ligand. Patients with active SLE who received telitacicept were prospectively followed at month 1, 3, 6, 9, and 12 after telitacicept initiation. Thirty-seven participants were involved and followed for 6.00 [3.00, 6.00] months. SRI-4 rate at month 6 was 44.7%. The median dosage of prednisone was decreased by 43.8% (from 10 to 5.62 mg/d) at month 6. The anti-dsDNA level was significantly decreased, while complement levels were significantly increased at month 6 from baseline. Continuously significant reductions in serum immunoglobin (Ig)G IgA, and IgM levels were also observed. Patients experienced significant decreases in the numbers of total and naive B cells, whereas memory B cells and T cell populations did not change. The number of NK cells was significantly increased during the follow-up. At month 6, 58.3% (14 out of 24) patients experienced improved fatigue accessed by FACIT-Fatigue score exceeding the minimum clinically important difference of 4. Most adverse events were mild, but one each case of severe hypogammaglobulinemia, psychosis with suicidal behavior, and B-cell lymphoma were occurred. In our first prospective real-world study, telitacicept treatment led to a significant clinical and laboratory improvement of disease activity, as well as fatigue amelioration in patients with SLE. Safety profile was favorable overall, but more studies are greatly needed.

Outcomes and prognosis of haploidentical haematopoietic stem cell transplantation in children with FLT3-ITD mutated acute myeloid leukaemia.

The presence of internal tandem duplication mutations in the FMS-like tyrosine kinase 3 receptor (FLT3-ITD) is a poor prognostic predictor in paediatric patients with acute myeloid leukaemia (AML). We evaluated the treatment outcomes and prognostic factors of 45 paediatric patients with FLT3-ITD AML who achieved complete remission before haploidentical haematopoietic stem cell transplantation (haplo-HSCT) at our institution from 2012 to 2021. Among the 45 patients, the overall survival (OS), event­free survival (EFS), and cumulative incidence of relapse (CIR) rates were 74.9% ± 6.6%, 64.1% ± 7.2%, and 31.4% ± 7.1%, respectively, with 48.8 months of median follow-up. Univariate and multivariate analyses associated positive minimal residual disease (MRD) at pre-HSCT and non-remission (NR) after introduce 1 with inferior long-term survival. The 100-day cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 35.6% ± 5.2%, and that of grade III-IV aGVHD was 15.6% ± 3.0% The overall 4-year cumulative incidence of chronic graft-versus-host disease after transplantation was 35.7% ± 9.8%, respectively. In conclusion, haplo-HSCT may be a feasible strategy for paediatric patients with FLT3-ITD AML, and pre-HSCT MRD status and NR after introduce 1 significantly affected the outcomes.

Clinical characteristics and outcomes of allogeneic hematopoietic stem cell transplantation recipients with coronavirus disease 2019 caused by the Omicron variant: a prospective, observational cohort study.

We aimed to describe the clinical characteristics, particularly the occurrence and risk factors of severe/critical illness, in allogeneic hematopoietic stem cell (allo-HSCT) recipients infected with coronavirus disease 2019 (COVID-19) caused by Omicron variant in an observational prospective study (n = 311). The median time from allo-HSCT to COVID-19 diagnosis was 8.5 months (range 0.8-106.1) months. Four patients (1.3%) were reported to be asymptomatic during Omicron variant infection, and 135 (43.4%) patients showed lower respiratory tract disease. Thirty-four (10.9%) patients were categorized into serious infection (severe illness n = 25; critical illness n = 9) and the median duration from COVID-19 diagnosis to serious infections was 6 days (range, 0-29) days. Thirteen (4.2%) and 6 (1.9%) patients required intensive care unit care and invasive mechanical ventilation, respectively. Receiving more than 1 type of immunosuppressive therapies at COVID-19 diagnosis was associated with severity and persistence of infection. Six patients (1.9%) died after diagnosis of COVID-19 infection. The 4-week probability of overall survival after COVID-19 diagnosis was 98.7%, which was 100% and 88.2% for non-serious and serious infection group (P < 0.001), respectively. Thus, we observed a relatively low serious infection and mortality rate in allo-HSCT recipients infected with COVID-19 caused by Omicron variant.

AURKA Enhances the Glycolysis and Development of Ovarian Endometriosis Through ERß.

Ovarian endometriosis (EMs) is a benign, estrogen-dependent gynecological disorder. Estrogen receptor beta (ERß), a nuclear receptor for estradiol, plays an important role in the development of ovarian EMs. Here, we investigated the biological significance of aurora kinase A (AURKA) in ovarian EMs and the mechanism by which it regulates ERß. We used immunohistochemical assays to verify that AURKA and ERß were highly expressed in ectopic endometrial tissues. Cell proliferation and colony formation assays were used to demonstrate that AURKA promoted the proliferation of EMs cells. Wound-healing assay, Transwell migration assay, and Matrigel invasion assay further showed that AURKA enhanced the ability of EMs cells to migrate and invade. In addition, AURKA was shown to stimulate glycolysis in EMs cells by measuring the concentration of glucose and lactate in the cell supernatants. Moreover, the AURKA inhibitor alisertib was found to inhibit the progression of ovarian EMs and glycolysis in a mouse model of EMs by measuring ectopic tissues as well as by testing the peritoneal fluid of mice. Furthermore, coimmunoprecipitation assay showed that AURKA interacted with ERß. The rescue experiments confirmed that AURKA regulated the development and glycolysis of ovarian EMs in an ERß-dependent manner. AURKA contributed to the development of ovarian EMs by upregulating of ERß. AURKA may represent a new target for the treatment of ovarian EMs.

Functional and Degradable Polyester-co-polyethers from CO2, Butadiene, and Epoxides.

Carbon dioxide (CO2), as a renewable and nontoxic C1 feedstock, has been recognized as an ideal comonomer to prepare sustainable materials. In this regard, substantial focus has been dedicated to the ring-opening copolymerization of CO2 and epoxides, which results in the creation of aliphatic polycarbonates in most cases. Here, we report an unprecedented strategy to synthesize functional and degradable polyester-co-polyethers from CO2, butadiene, and epoxides via a CO2/butadiene-derived δ-valerolactone intermediate (EVP). Utilizing a chromium salen complex as the catalyst, the copolymerization of EVP and epoxides was successfully achieved to produce CO2/butadiene/epoxide terpolymers. The obtained polyester-co-polyethers with varied 39-93 mol % EVP content (equal to 18-28 wt % CO2 incorporation) show high thermal stability, tunable glass-transition temperatures, on-demand functionality, and good chemical degradability. This method extends the potential to access functional CO2-based polymers.