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2.
Exp Hematol Oncol ; 11(1): 25, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35505384

RESUMO

BACKGROUND: Acute graft-versus-host disease (aGVHD) remains the major cause of early mortality after haploidentical related donor (HID) hematopoietic stem cell transplantation (HSCT). We aimed to establish a comprehensive model which could predict severe aGVHD after HID HSCT. METHODS: Consecutive 470 acute leukemia patients receiving HID HSCT according to the protocol registered at https://clinicaltrials.gov (NCT03756675) were enrolled, 70% of them (n = 335) were randomly selected as training cohort and the remains 30% (n = 135) were used as validation cohort. RESULTS: The equation was as follows: Probability (grade III-IV aGVHD) = [Formula: see text], where Y = -0.0288 × (age) + 0.7965 × (gender) + 0.8371 × (CD3 + /CD14 + cells ratio in graft) + 0.5829 × (donor/recipient relation) - 0.0089 × (CD8 + cell counts in graft) - 2.9046. The threshold of probability was 0.057392 which helped separate patients into high- and low-risk groups. The 100-day cumulative incidence of grade III-IV aGVHD in the low- and high-risk groups was 4.1% (95% CI 1.9-6.3%) versus 12.8% (95% CI 7.4-18.2%) (P = 0.001), 3.2% (95% CI 1.2-5.1%) versus 10.6% (95% CI 4.7-16.5%) (P = 0.006), and 6.1% (95% CI 1.3-10.9%) versus 19.4% (95% CI 6.3-32.5%) (P = 0.017), respectively, in total, training, and validation cohort. The rates of grade III-IV skin and gut aGVHD in high-risk group were both significantly higher than those of low-risk group. This model could also predict grade II-IV and grade I-IV aGVHD. CONCLUSIONS: We established a model which could predict the development of severe aGVHD in HID HSCT recipients.

3.
Plant Divers ; 44(2): 153-162, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35505982

RESUMO

Spurs have played an important role in the radiation of the genus Aquilegia, but little is known about how the spurless state arose in A. ecalcarata. Here we aim to characterize the genetic divergence within A. ecalcarata and gain insights into the origin of this species. A total of 19 populations from A. ecalcarata and 23 populations from three of its closest relatives (Aquilegia kansuensis, Aquilegia rockii and Aquilegia yabeana) were sampled in this study. We sequenced fifteen nuclear gene fragments across the genome and three chloroplast loci to conduct phylogenetic, PCoA and STRUCTURE analyses. Our analyses indicate that A. ecalcarata may not be monophyletic and can be divided into two distinct lineages (A. ecalcarata I and A. ecalcarata II). A. ecalcarata I is genetically close to A. kansuensis, whereas A. ecalcarata II is close to A. rockii. Isolation-with-migration analysis suggested that historical gene flow was low between A. ecalcarata I and A. rockii, as well as between A. ecalcarata II and A. kansuensis. The two distinct lineages of A. ecalcarata show significant divergence in 13 floral traits and also have distinct distributions. In addition, both A. ecalcarata I and II are adapted to a stony environment that differs from that of their closest relatives, indicating a habitat shift may have driven new adaptations. Our findings enrich the understanding of how floral evolution contributes to species diversification.

4.
Ther Adv Hematol ; 13: 20406207221095226, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35510211

RESUMO

Background: The responses of intravenous immunoglobulin (IVIg) or corticosteroids as the initial treatment on pregnancy with ITP were unsatisfactory. This study aimed to assess the safety and effectiveness of prednisone plus IVIg versus prednisone or IVIg in pregnant patients with immune thrombocytopenia (ITP). Methods: Between 1 January 2010 and 31 December 2020, 970 pregnancies diagnosed with ITP at 19 collaborative centers in China were reviewed in this observational study. A total of 513 pregnancies (52.89%) received no intervention. Concerning the remaining pregnancies, 151 (33.04%) pregnancies received an initial treatment of prednisone plus IVIg, 105 (22.98%) pregnancies received IVIg alone, and 172 (37.64%) pregnancies only received prednisone. Results: Regarding the maternal response to the initial treatment, no differences were found among the three treatment groups (41.1% for prednisone plus IVIg, 33.1% for prednisone, and 38.1% for IVIg). However, a significant difference was observed in the time to response between the prednisone plus IVIg group (4.39 ± 2.54 days) and prednisone group (7.29 ± 5.01 days; p < 0.001), and between the IVIg group (6.71 ± 4.85 days) and prednisone group (p < 0.001). The median prednisone duration in the monotherapy group was 27 days (range, 8-195 days), whereas that in the combination group was 14 days (range, 6-85 days). No significant differences were found among these three treatment groups in neonatal outcomes, particularly concerning the neonatal platelet counts. The time to response in the combination treatment group was shorter than prednisone monotherapy. The duration of prednisone application in combination group was shorter than prednisone monotherapy. The combined therapy showed a lower predelivery platelet transfusion rate than IVIg alone. Conclusion: These findings suggest that prednisone plus IVIg may represent a potential combination therapy for pregnant patients with ITP.

5.
RSC Adv ; 12(3): 1728-1737, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-35425158

RESUMO

In this paper, using hollow silica microspheres as carriers, we developed a facile one-pot method for the preparation of hollow SiO2@MnO2 composite microparticles. Under a certain proportion of hollow silica microspheres and manganese salt, a novel kind of hollow urchin-like SiO2@γ-MnO2 microparticles was obtained. The structure and morphology of the composite microparticles were characterized by XRD, SEM and TEM. On this basis, using rhodamine B and methyl orange as model molecules, the oxidative degradation ability of the hollow SiO2@γ-MnO2 microparticles for organic dyes in water was investigated through UV-vis analysis technology. The urchin-like SiO2@γ-MnO2 microparticles showed excellent performance for the rapid oxidative degradation of organic dyes under acidic conditions. This study indicated that γ-MnO2 loaded on hollow materials can be used as an efficient tool for treating organic dye wastewater, and shows broad application prospects for solving environmental problems in the related industry.

6.
BMC Med ; 20(1): 140, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35473809

RESUMO

BACKGROUND: Poor graft function (PGF) or prolonged isolated thrombocytopenia (PT), which are characterized by pancytopenia or thrombocytopenia, have become serious complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our previous single-arm trial suggests that N-acetyl-L-cysteine (NAC) prophylaxis reduced PGF or PT after allo-HSCT. Therefore, an open-label, randomized, phase 3 trial was performed to investigate the efficacy and tolerability of NAC prophylaxis to reduce PGF or PT after allo-HSCT. METHODS: A phase 3, open-label randomized trial was performed. Based on the percentage of CD34+VEGFR2 (CD309)+ endothelial cells (ECs) in bone marrow (BM) detected by flow cytometry at 14 days before conditioning, patients aged 15 to 60 years with acute leukemia undergoing haploidentical HSCT were categorized as low-risk (EC ≥ 0.1%) or high-risk (EC < 0.1%); patients at high risk were randomly assigned (2:1) to receive NAC prophylaxis or nonprophylaxis. The primary endpoint was PGF and PT incidence at +60 days post-HSCT. RESULTS: Between April 18, 2019, and June 24, 2021, 120 patients with BM EC <0.1% were randomly assigned for NAC (group A, N = 80) or nonprophylaxis (group B, N = 40), and 105 patients with EC≥0.1% (group C) were also analyzed. The +60 days incidence of PGF and PT was 7.5% (95% CI, 1.7 to 13.3%) and 22.5% (95% CI, 9.1 to 35.9%) in group A and group B (hazard ratio, 0.317; 95% CI, 0.113 to 0.890; P = 0.021) and 11.4% (95% CI, 5.2 to 17.6%) in group C (hazard ratio, 0.643; 95% CI, 0.242 to 1.715; P = 0.373). Consistently, NAC prophylaxis gradually improved BM ECs and CD34+ cells in group A, whereas reduced their reactive oxygen species (ROS) levels post-HSCT. Within 60 days post-HSCT, the most common grade 3 to 5 adverse events for the NAC and control groups were infections (19/80 [24%] vs. 10/40 [25%]) and gastrointestinal adverse events (16/80 [20%] vs. 7/40 [18%]). There were no treatment-related deaths. CONCLUSIONS: N-Acetyl-L-cysteine prophylaxis can prevent the occurrence of poor hematopoietic function and is well tolerated in haploidentical HSCT. It may offer a potential pathogenesis-oriented therapeutic approach for patients with poor hematopoietic function. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov as #NCT03967665.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Trombocitopenia , Acetilcisteína/uso terapêutico , Células Endoteliais , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Prostaglandinas F , Trombocitopenia/etiologia
7.
Front Cell Infect Microbiol ; 12: 862526, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35392613

RESUMO

Objective: We aimed to establish a model that can predict refractory/recurrent cytomegalovirus (CMV) infection after haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT). Methods: Consecutive acute leukemia patients receiving HID HSCT were enrolled (n = 289). We randomly selected 60% of the entire population (n = 170) as the training cohort, and the remaining 40% comprised the validation cohort (n = 119). Patients were treated according to the protocol registered at https://clinicaltrials.gov (NCT03756675). Results: The model was as follows: Y = 0.0322 × (age) - 0.0696 × (gender) + 0.5492 × (underlying disease) + 0.0963 × (the cumulative dose of prednisone during pre-engraftment phase) - 0.0771 × (CD34+ cell counts in graft) - 1.2926. The threshold of probability was 0.5243, which helped to separate patients into high- and low-risk groups. In the low- and high-risk groups, the 100-day cumulative incidence of refractory/recurrent CMV was 42.0% [95% confidence interval (CI), 34.7%-49.4%] vs. 63.7% (95% CI, 54.8%-72.6%) (P < 0.001) for total patients and was 50.5% (95% confidence interval (CI), 40.9%-60.1%) vs. 71.0% (95% CI, 59.5%-82.4%) (P = 0.024) for those with acute graft-versus-host disease. It could also predict posttransplant mortality and survival. Conclusion: We established a comprehensive model that could predict the refractory/recurrent CMV infection after HID HSCT. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT03756675.


Assuntos
Infecções por Citomegalovirus , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Doença Aguda , Infecções por Citomegalovirus/etiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Recém-Nascido , Leucemia Mieloide Aguda/etiologia , Leucemia Mieloide Aguda/terapia , Estudos Retrospectivos
8.
BMC Infect Dis ; 22(1): 292, 2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35346077

RESUMO

BACKGROUND: Invasive fungal disease (IFD) is a severe complication after haploidentical stem cell transplantation (haplo-HSCT) and has a poor prognosis. It has been shown that genetic polymorphism may be one possible reason for the increased risk of IFD. This study aimed to assess the role of genetic polymorphism in the level of susceptibility to IFD after haplo-HSCT. METHODS: In this study, we prospectively enrolled 251 patients who received haplo-HSCT at the Peking University Institute of Hematology from 2016 to 2018. Forty-three single nucleotide polymorphisms (SNPs) of the genomic DNA were genotyped in blood samples from both recipient and donor. RESULTS: Twenty-two patients (8.8%) were diagnosed with proven or probable IFD. The independent risk factors for IFD were grades 3-4 acute graft-versus-host disease, cytomegalovirus reactivation, and recipient and donor rs2305619 (PTX3) (P < 0.05) in multivariate analysis. Meanwhile, we combined the variables to develop the IFD risk scoring system and stratified patients into low- (0-2) and high-risk (3-4) groups. The 30-day and 100-day cumulative incidence of IFD in the low- and high-risk groups were 2.1% and 10.2%, 4.2% and 20.3%, respectively (P = 0.015). CONCLUSIONS: PTX3 rs2305619 polymorphism increase the susceptibility of IFD after haplo-HSCT in the Chinese Han population, and the IFD scoring system could be useful in risk stratification for IFD after HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Infecções Fúngicas Invasivas , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Infecções Fúngicas Invasivas/genética , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Transplante Homólogo/efeitos adversos
9.
J Transl Med ; 20(1): 144, 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35351133

RESUMO

BACKGROUND: Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid clonal disorders characterized by ineffective haematopoiesis and immune deregulation. Emerging evidence has shown the effect of bone marrow (BM) endothelial progenitor cells (EPCs) in regulating haematopoiesis and immune balance. However, the number and functions of BM EPCs in patients with different stages of MDS remain largely unknown. METHODS: Patients with MDS (N = 30), de novo acute myeloid leukaemia (AML) (N = 15), and healthy donors (HDs) (N = 15) were enrolled. MDS patients were divided into lower-risk MDS (N = 15) and higher-risk MDS (N = 15) groups according to the dichotomization of the Revised International Prognostic Scoring System. Flow cytometry was performed to analyse the number of BM EPCs. Tube formation and migration assays were performed to evaluate the functions of BM EPCs. In order to assess the gene expression profiles of BM EPCs, RNA sequencing (RNA-seq) were performed. BM EPC supporting abilities of haematopoietic stem cells (HSCs), leukaemia cells and T cells were assessed by in vitro coculture experiments. RESULTS: Increased but dysfunctional BM EPCs were found in MDS patients compared with HDs, especially in patients with higher-risk MDS. RNA-seq indicated the progressive change and differences of haematopoiesis- and immune-related pathways and genes in MDS BM EPCs. In vitro coculture experiments verified that BM EPCs from HDs, lower-risk MDS, and higher-risk MDS to AML exhibited a progressively decreased ability to support HSCs, manifested as elevated apoptosis rates and intracellular reactive oxygen species (ROS) levels and decreased colony-forming unit plating efficiencies of HSCs. Moreover, BM EPCs from higher-risk MDS patients demonstrated an increased ability to support leukaemia cells, characterized by increased proliferation, leukaemia colony-forming unit plating efficiencies, decreased apoptosis rates and apoptosis-related genes. Furthermore, BM EPCs induced T cell differentiation towards more immune-tolerant cells in higher-risk MDS patients in vitro. In addition, the levels of intracellular ROS and the apoptosis ratios were increased in BM EPCs from MDS patients, especially in higher-risk MDS patients, which may be therapeutic candidates for MDS patients. CONCLUSION: Our results suggest that dysfunctional BM EPCs are involved in MDS patients, which indicates that improving haematopoiesis supporting ability and immuneregulation ability of BM EPCs may represent a promising therapeutic approach for MDS patients.


Assuntos
Células Progenitoras Endoteliais , Síndromes Mielodisplásicas , Apoptose , Medula Óssea , Células-Tronco Hematopoéticas , Humanos , Síndromes Mielodisplásicas/genética
10.
Haematologica ; 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35354250

RESUMO

Bone marrow(BM) endothelial progenitor cell(EPC) damage with unknown mechanism delays the repair of endothelial cells(ECs) and hematopoiesis recovery after chemo-radiotherapy. Herein, enhanced glycolytic enzyme PFKFB3 was demonstrated in the damaged BM EPCs of patients with poor graft function(PGF), a clinical model of EPC damage-associated poor hematopoiesis after allogeneic hematopoietic stem cell transplantation(allo-HSCT). Moreover, glycolysis inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one(3PO) alleviated the damaged BM EPCs of PGF patients in vitro. Consistently, PFKFB3 overexpression triggered BM EPC damage after 5FU treatment and impaired hematopoiesis-supporting ability in vitro. Mechanismly, PFKFB3 facilitated pro-apoptotic transcription factor FOXO3A and its downstream gene expressions, including p21, p27, FAS after 5FU treatment in vitro. Moreover, PFKFB3 induced NF-κB activation and its downstream adhesion molecule E-selectin expression, while reduced hematopoietic factor SDF-1 expression, which could be rescued by FOXO3A silence. Highly expressed PFKFB3 was found in damaged BM ECs of chemo-radiotherapy-induced myelosuppression murine models. Furthermore, the BM EC-specific PFKFB3 overexpression murine model demonstrated that PFKFB3 aggravated BM EC damage, and impaired hematopoiesis recovery after chemotherapy in vivo, which could be improved by 3PO, indicating a critical role of PFKFB3 in regulating BM EC damage. Clinically, PFKFB3-induced FOXO3A expression and NF-κB activation were confirmed to contribute to the damaged BM EPCs of patients with acute leukemia after chemotherapy. 3PO repaired the damaged BM EPCs by reducing FOXO3A expression and phospho-NF-κB p65 in patients after chemotherapy. In summary, our results reveal a critical role of PFKFB3 in triggering BM EPC damage and indicate that endothelial-PFKFB3 may be a potential therapeutic target for myelosuppressive injury.

11.
Am J Hematol ; 97(6): 762-769, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35293011

RESUMO

Adoptive therapy with cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CMV-CTLs) has emerged as an effective method for CMV infection. However, the efficacy reportedly ranges from 50% to 90%, and factors affecting anti-CMV efficacy have not been established. We investigated the safety and efficacy of adoptive therapy with CMV-CTLs for CMV infection in 190 patients after haploidentical stem cell transplantation (haplo-SCT), and importantly, we analyzed the main factors affecting antiviral efficacy. The CMV peak titer decreased from 19 (range, 1.0-503.0) × 103 copies/mL to 3.9 (range, 0-112) × 103 copies/mL after CMV-CTL infusion. The cumulative complete response (CR) rates in the first, fourth, and sixth weeks after the first CMV-CTL infusion were 37.9% (95% CI 35.0-40.8), 76.8% (95% CI 70.7-82.9), and 89.5% (95% CI 85.2-93.8), respectively. In multivariate analysis, persistent CMV infection prior to CMV-CTL infusion (hazard ratio [HR] 2.29, 95% CI 1.29-4.06, p = .005) and basiliximab treatment within 2 weeks of CMV-CTL infusion (HR 1.87, 95% CI 1.06-3.81, p = .031) were independent predictors of poor antiviral efficacy of CMV-CTL therapy. Our data showed that adoptive therapy with CMV-CTLs is a safe and effective treatment for CMV infection after haplo-SCT. Persistent CMV infection and basiliximab treatment are correlated with poor anti-CMV efficacy of CMV-CTL therapy.


Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Antivirais/uso terapêutico , Basiliximab/uso terapêutico , Citomegalovirus , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Transplante de Células-Tronco , Linfócitos T Citotóxicos
12.
Front Immunol ; 13: 757002, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35154096

RESUMO

For allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, preemptive interferon-α (IFN-α) therapy is considered as a useful method to eliminate the minimal residual disease (MRD). Our purpose is to assess the long-term efficacy of preemptive IFN-α therapy in acute myeloid leukemia (AML) patients following allo-HSCT based on two registry studies (#NCT02185261 and #NCT02027064). We would present the final data and unpublished results of long-term clinical outcomes with extended follow-up. We adopted polymerase chain reaction (PCR) and multiparameter flow cytometry (MFC) to monitor MRD, and a positive result of bone marrow specimen examined by either of them would be identified as the MRD-positive status. Subcutaneous injections of recombinant human IFN-α-2b were performed for 6 cycles, and prolonged IFN-α therapy could be permitted at the request of patients. The median cycles were 3.5 (range, 0.5-30.5) cycles. A total of 9 patients suffered from grade ≥3 toxicities (i.e., infectious: n = 6; hematologic: n = 3). The 6-year cumulative incidences of relapse and non-relapse mortality following IFN-α therapy were 13.0% (95% confidence interval [CI], 5.4-20.6%) and 3.9% (95%CI, 0.0-17.6%), respectively. The probability of disease-free survival at 6 years following IFN-α therapy was 83.1% (95%CI, 75.2-91.9%). The probability of overall survival at 6 years following IFN-α therapy was 88.3% (95%CI, 81.4-95.8%). The cumulative incidences of total chronic graft-versus-host disease (cGVHD) and severe cGVHD at 6 years following IFN-α therapy were 66.2% (95%CI, 55.5-77.0%) and 10.4% (95%CI, 3.6-17.2%), respectively. Multivariable analysis showed that an alternative donor was associated with a lower risk of relapse and the better disease-free survival. Thus, preemptive IFN-α therapy could clear MRD persistently, prevent relapse truly, and improve long-term survival in AML patients following allo-HSCT.


Assuntos
Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Fatores Imunológicos/administração & dosagem , Interferon alfa-2/administração & dosagem , Leucemia Mieloide Aguda/terapia , Sistema de Registros , Prevenção Secundária/métodos , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Idoso , Criança , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Injeções Subcutâneas , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Estudos Prospectivos , Recidiva , Transplante Homólogo/efeitos adversos , Adulto Jovem
13.
Insights Imaging ; 13(1): 21, 2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35122162

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a malignancy with poor prognosis, appropriate surgical resection and neoadjuvant therapy depend on the accurate identification of pancreatic supplying arteries. We aim to evaluate the ability of monoenergetic images (MEI [+]) of dual-energy CT (DECT) to improve the visualization of pancreatic supplying arteries compared to conventional polyenergetic images (PEI) and investigate the implications of vascular variation in pancreatic surgery and transarterial interventions. RESULTS: One hundred patients without pancreatic diseases underwent DECT examinations were retrospectively enrolled in this study. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) at 40-keV MEI (+) were significantly higher than those of PEI (p < 0.05). All subjective MEI (+) scores were significantly higher than those of PEI (p < 0.05). The visualization rates were significantly higher for posterior superior pancreaticoduodenal artery (PSPDA), anterior and posterior inferior pancreaticoduodenal artery (AIPDA, PIPDA), anterior and posterior pancreaticoduodenal arcade (APAC, PPAC), transverse and caudal pancreatic artery (TPA, PCA) at 40-keV MEI (+) than those of PEI (p < 0.05). However, there were no significant differences for visualizing anterior superior pancreaticoduodenal artery (ASPDA), inferior pancreaticoduodenal artery (IPDA), dorsal and magnificent pancreatic artery (DPA, MPA) between 40-keV MEI (+) and PEI (p > 0.05). Four types of variations were observed in the origin of DPA and three to five types in the origin of PSPDA, AIPDA and PIPDA. CONCLUSIONS: 40-keV MEI (+) of DECT improves the visualization and objective and subjective image quality of pancreatic supplying arteries compared to PEI. Pancreatic supplying arteries have great variations, which has important implications for preoperative planning of technically challenging surgeries and transarterial interventions.

14.
Physiol Behav ; 249: 113744, 2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35183563

RESUMO

Mate choice was an important factor affecting the success rate of natural mating of captive giant pandas. The influencing factors and mechanisms of the mate preference of captive giant pandas were still unclear, and it was speculated that they might be related to the psychological stress caused by the long-term confined environment restricting their free choice of physiological needs. In order to test this hypothesis, this work explored the urinary metabolites of 6 adult captive male giant pandas during breeding period. Differences in metabolite levels in giant panda urine samples were analyzed via Ultra High Performance LC-MS (UHPLC/-MS) comparing preservation to loss of natural reproductive capacity and success to failure of mating choice, trying to understand the psychological feelings of captive giant pandas in the process of mate choice from the perspective of all metabolites and related biochemical pathways, and fully revealed the mechanism of decline of their natural reproductive ability. The analysis results indicated that the loss of natural mating behavior of adult captive male giant pandas might be related to the disorder of tryptophan metabolism pathway and inhibition of arginine synthesis; the reason for the failure of mating choice caused by decreased libido might be related to the temporary decrease of androgen contents caused by the down-regulated of TCA cycle function and galactose metabolic pathway. These findings not only provide that adult male giant pandas in captivity do have psychological frustration caused by the inability to freely choose their favorite mate or failure of mating preference, but also showed that the changes in stress-related metabolic pathways caused by psychological frustration were an important reason for the decline of natural mating behavior of adult captive male giant pandas.


Assuntos
Ursidae , Androgênios/metabolismo , Animais , Masculino , Espectrometria de Massas , Metabolômica , Reprodução , Ursidae/metabolismo , Ursidae/urina
15.
J Viral Hepat ; 29(5): 306-316, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35152507

RESUMO

Patients with hepatitis B-related cirrhosis complicated with thrombocytopenia have a higher risk of bleeding, which may lead to higher mortality. We aimed to explore the efficacy and safety of recombinant human thrombopoietin (rhTPO) in the treatment of hepatitis B-related cirrhosis complicated with severe thrombocytopenia. Patients with hepatitis B-related compensated liver cirrhosis complicated with severe thrombocytopenia were divided into four groups according to the treatment method for thrombocytopenia. Platelet counts, the appearance of bleeding symptoms and adverse events were evaluated during the observation period. Also during the observational period, the platelet counts in the prednisone group, rhTPO group and prednisone plus rhTPO group were higher than those in the no treatment group. Patients without splenomegaly reacted better to rhTPO. Fewer bleeding events of grade 2 or worse were observed in the three treatment groups compared to the no treatment group. The platelet counts at baseline and treatment with rhTPO and/or prednisone were factors associated with bleeding events of grade 2 or worse in multivariate analysis. There could be a potential advantage for the use of rhTPO plus prednisone based on higher platelet counts and fewer bleeding events. Treatment with rhTPO was more effective in patients without splenomegaly.


Assuntos
Hepatite B , Trombocitopenia , Hepatite B/complicações , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Contagem de Plaquetas , Prednisona , Proteínas Recombinantes/efeitos adversos , Esplenomegalia/complicações , Trombocitopenia/complicações , Trombocitopenia/tratamento farmacológico , Trombopoetina/efeitos adversos
16.
BMC Cancer ; 22(1): 11, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34979982

RESUMO

BACKGROUND: The mixed-lineage leukemia (MLL) gene is located on chromosome 11q23. The MLL gene can be rearranged to generate partial tandem duplications (MLL-PTD), which occurs in about 5-10% of acute myeloid leukemia (AML) with a normal karyotype and in 5-6% of myelodysplastic syndrome (MDS) patients. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently one of the curative therapies available for AML and MDS with excess blasts (MDS-EB). However, how the prognosis of patients with high levels of MLL-PTD after allo-HSCT, and whether MLL-PTD could be used as a reliable indicator for minimal residual disease (MRD) monitoring in transplant patients remains unknown. Our study purposed to analyze the dynamic changes of MLL-PTD peri-transplantation and the best threshold for predicting relapse after transplantation. METHODS: We retrospectively collected the clinical data of 48 patients with MLL-PTD AML or MDS-EB who underwent allo-HSCT in Peking University People's Hospital. The MLL-PTD was examined by real-time quantitative polymerase chain reaction (RQ-PCR) at the diagnosis, before transplantation and the fixed time points after transplantation. Detectable MLL-PTD/ABL > 0.08% was defined as MLL-PTD positive in this study. RESULTS: The 48 patients included 33 AML patients and 15 MDS-EB patients. The median follow-up time was 26(0.7-56) months after HSCT. In AML patients, 7 patients (21.2%) died of treatment-related mortality (TRM), 6 patients (18.2%) underwent hematological relapse and died ultimately. Of the 15 patients with MDS-EB, 2 patients (13.3%) died of infection. The 3-year cumulative incidence of relapse (CIR), overall survival (OS), disease-free survival (DFS) and TRM were 13.7 ± 5.2, 67.8 ± 6.9, 68.1 ± 6.8 and 20.3% ± 6.1%, respectively. ROC curve showed that post-transplant MLL-PTD ≥ 1.0% was the optimal cut-off value for predicting hematological relapse after allo-HSCT. There was statistical difference between post-transplant MLL-PTD ≥ 1.0% and MLL-PTD < 1.0% groups (3-year CIR: 75% ± 15.3% vs. 0%, P < 0.001; 3-year OS: 25.0 ± 15.3% vs. 80.7% ± 6.6%, P < 0.001; 3-year DFS: 25.0 ± 15.3% vs. 80.7 ± 6.6%, P < 0.001; 3-year TRM: 0 vs. 19.3 ± 6.6%, P = 0.277). However, whether MLL-PTD ≥ 1% or MLL-PTD < 1% before transplantation has no significant difference on the prognosis. CONCLUSIONS: Our study indicated that MLL-PTD had a certain stability and could effectively reflect the change of tumor burden. The expression level of MLL-PTD after transplantation can serve as an effective indicator for predicting relapse.


Assuntos
Histona-Lisina N-Metiltransferase/genética , Leucemia Mieloide Aguda/genética , Síndromes Mielodisplásicas/genética , Proteína de Leucina Linfoide-Mieloide/genética , Recidiva Local de Neoplasia/genética , Proteínas de Fusão Oncogênica/genética , Intervalo Livre de Doença , Feminino , Seguimentos , Rearranjo Gênico/genética , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/cirurgia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/cirurgia , Recidiva Local de Neoplasia/mortalidade , Neoplasia Residual , Período Pós-Operatório , Valor Preditivo dos Testes , Prognóstico , Intervalo Livre de Progressão , Recidiva , Estudos Retrospectivos , Transplante Homólogo , Carga Tumoral/genética
17.
JCI Insight ; 7(3)2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-34990406

RESUMO

CMV infection remains an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several investigators have reported that adaptive NKG2C+ NK cells persistently expand during CMV reactivation. In our study, 2 cohorts were enrolled to explore the relationships among the NKG2C genotype, NKG2C+ NK cell reconstitution, and CMV infection. Multivariate analysis showed that donor NKG2C gene deletion was an independent prognostic factor for CMV reactivation and refractory CMV reactivation. Furthermore, adaptive NKG2C+ NK cells' quantitative and qualitative reconstitution, along with their anti-CMV function after transplantation, was significantly lower in patients grafted with NKG2Cwt/del donor cells than in those grafted with NKG2Cwt/wt donor cells. At day 30 after transplantation, quantitative reconstitution of NKG2C+ NK cells was significantly lower in patients with treatment-refractory CMV reactivation than in patients without CMV reactivation and those with nonrefractory CMV reactivation. In humanized CMV-infected mice, we found that, compared with those from NKG2Cwt/del donors, adaptive NKG2C+ NK cells from NKG2Cwt/wt donors induced earlier and stronger expansion of NKG2C+ NK cells as well as earlier and stronger CMV clearance in vivo. In conclusion, donor NKG2C homozygosity contributes to CMV clearance by promoting the quantitative and qualitative reconstruction of adaptive NKG2C+ NK cells after haploidentical allo-HSCT.


Assuntos
Infecções por Citomegalovirus/genética , Rejeição de Enxerto/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Células Matadoras Naturais/patologia , Mutação , Subfamília C de Receptores Semelhantes a Lectina de Células NK/genética , Doadores de Tecidos , Adolescente , Adulto , Animais , Linhagem Celular , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/virologia , DNA/genética , Análise Mutacional de DNA , Feminino , Seguimentos , Rejeição de Enxerto/metabolismo , Rejeição de Enxerto/patologia , Homozigoto , Humanos , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/virologia , Masculino , Camundongos , Pessoa de Meia-Idade , Subfamília C de Receptores Semelhantes a Lectina de Células NK/metabolismo , Estudos Prospectivos , Transplante Haploidêntico , Ativação Viral , Adulto Jovem
18.
Cell Mol Immunol ; 19(4): 482-491, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35017718

RESUMO

Adoptive transfer of cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CMV-CTLs) from original transplant donors or third-party donors was effective for the treatment of CMV infection after allogenic stem cell transplantation (allo-SCT), but the antiviral activity of CMV-CTL types has not been compared. To determine whether third-party CMV-CTLs provide comparable long-term antiviral efficacy to transplant donor CMV-CTLs, we first compared the antiviral abilities of transplant donors and third-party CMV-CTLs for treatment of CMV infection in two mouse models, compared the in vivo recovery of CMV-specific immunity, and analyzed the underlying mechanisms driving sustained antiviral immunity. The results showed that both donor and third-party CMV-CTLs effectively combated systemic CMV infection by reducing CMV pathology and tumor burden 28 days postinfusion. The in vivo recovery of CMV-specific immunity after CMV-CTL infusion was comparable in both groups. A detailed analysis of the source of recovered CMV-CTLs showed the proliferation and expansion of graft-derived endogenous CMV-CTLs in both groups. Our clinical study, which enrolled 31 patients who received third-party CMV-CTLs and 62 matched pairs of individuals who received transplant donor CMV-CTLs for refractory CMV infection, further showed that adoptive therapy with donor or third-party CMV-CTLs had comparable clinical responses without significant therapy-related toxicity. We observed strong expansion of CD8+ tetramer+ T cells and proliferation of recipient endogenous CMV-CTLs after CMV-CTL infusion, which were associated with a reduced or cleared viral load. Our data confirmed that adoptive therapy with third-party or transplant donor CMV-CTLs triggered comparable antiviral responses to CMV infection that might be mediated by restoration of endogenous CMV-specific immunity.


Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Animais , Citomegalovirus , Humanos , Camundongos , Transplante de Células-Tronco , Linfócitos T Citotóxicos , Doadores de Tecidos
19.
Ther Adv Hematol ; 13: 20406207211072838, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35096361

RESUMO

PURPOSE: Graft-versus-host disease (GVHD) is an important complication after human leukocyte antigen (HLA) haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT), which may lead to poor prognosis. Our study intends to identify the efficacy and safety of mesenchymal stem cells (MSCs) for multidrug-resistant (MDR)-GVHD after HID HSCT. METHODS: MDR-GVHD was referring to GVHD remaining no response to at least two types of therapy, and hUCB-MSCs were given at the dose of (1.0-2.0) × 106/kg once a week. RESULTS: A total of 21 patients were enrolled in this retrospective study (acute GVHD (aGVHD): n = 14, chronic GVHD (cGVHD): n = 7). The median dose of MSCs was 1.2 × 106 cells/kg (range, 0.8-1.8 × 106) cells/kg, and the median numbers of infusion were 2 (range, 1-7) and 3 (range, 2-12) for MDR-aGVHD and MDR-cGVHD patients, respectively. In MDR-aGVHD patients, the overall response rate (ORR) was 57.1%, including 50.0% complete response (CR) and 7.1% partial response (PR), and the median time to response was 49.5 days (range, 16-118) days. The 2-year probability of overall survival after MSCs was 64.3%. Five patients (35.7%) developed infections after MSCs, and no obvious hematologic toxicities were observed. Five MDR-aGVHD patients died after MSCs treatments because of GVHD progression (n = 1), severe infection (bacterial central nervous system infection: n = 1; fungal pneumonia: n = 2), and poor graft function (n = 1). In MDR-cGVHD patients, three patients (42.9%) achieved PR after MSCs and the median time to response was 56 days (22-84) days. The ORRs for moderate and severe cGVHD were 50.0% and 33.3%, respectively. Four MDR-cGVHD patients died after MSCs treatments because of GVHD progression (n = 2), severe fungal pneumonia (n = 1), and relapse (n = 1). CONCLUSION: MSCs treatment may be safe and effective for MDR-GVHD after HID HSCT.

20.
Bone Marrow Transplant ; 57(4): 554-561, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35079139

RESUMO

The efficacy and outcome of therapeutic plasma exchange (TPE) for transplant-associated thrombotic microangiopathy (TA-TMA) remain controversial. We therefore sought to evaluate the outcome and efficacy of TPE in patients with TA-TMA and to identify TA-TMA patients who would benefit from TPE management. Eighty-two patients with TA-TMA were treated with TPE. We reported a response rate of 52% and overall survival rates of 20% and 15% at 100 days and 1 year after TA-TMA, respectively, in TPE-treated patients, with a significantly lower survival in gastrointestinal (GI) bleeding patients (5% vs. 41% in non-GI bleeding patients, P = 0.003). Multivariate analysis revealed that patients with GI bleeding, grade III-IV aGVHD, severe anemia, and a lower cumulative volume of TPE were less likely to respond to TPE. GI bleeding, a lower initial volume of TPE, and elevated total bilirubin were independently associated with 100-day mortality. The leading causes of death were infection, active TA-TMA, and MODS. The results of this large cohort of real-world practice indicate that the efficacy and outcome of TPE for TA-TMA patients without GI bleeding are encouraging, and a higher volume of TPE is warranted to achieve favorable outcomes.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Microangiopatias Trombóticas , Estudos de Coortes , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Troca Plasmática/efeitos adversos , Troca Plasmática/métodos , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/terapia , Resultado do Tratamento
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