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OBJECTIVE: To investigate the effect of CD8+ CD28- T cells on acute graft-versus-host disease(aGVHD) after haploidentical hematopoietic stem cell transplantation(haplo-HSCT). METHODS: The relationship between absolute count of CD8+ CD28- T cells and aGVHD in 60 patients with malignant hematological diseases was retrospectively analyzed after haplo-HSCT, and the differences in the incidence rate of chronic graft-versus host disease(cGVHD), infection and prognosis between different CD8+ CD28- T absolute cells count groups were compared. RESULTS: aGVHD occurred in 40 of 60 patients after haplo-HSCT, with an incidence rate of 66.67%. The median occurrence time of aGVHD was 32.5(20-100) days. At 30 days after the transplantation, the absolute count of CD8+ CD28- T cells of aGVHD group was significantly lower than that of non-aGVHD group (P =0.03). Thus the absolute count of CD8+ CD28- T cells at 30 days after transplantation can be used to predict the occurrence of aGVHD to some extent. At 30 days after transplantation, the incidence rate of aGVHD in the low cell count group (CD8+ CD28- T cells absolute count < 0.06/µl) was significantly higher than that in the high cell count group (CD8+ CD28- T cells absolute count ≥0.06/µl,P =0.011). Multivariate Cox regression analysis further confirmed that the absolute count of CD8+ CD28-T cells at 30 days after transplantation was an independent risk factor for aGVHD, and the risk of aGVHD in the low cell count group was 2.222 times higher than that in the high cell count group (P =0.015). The incidence of cGVHD, fungal infection, EBV infection and CMV infection were not significantly different between the two groups with different CD8+ CD28- T cells absolute count. The overall survival, non-recurrent mortality and relapse rates were not significantly different between different CD8+ CD28- T cells absolute count groups. CONCLUSION: Patients with delayed CD8+ CD28- T cells reconstitution after haplo-HSCT are more likely to develop aGVHD, and the absolute count of CD8+ CD28- T cells can be used to predict the incidence of aGVHD to some extent. The absolute count of CD8+ CD28- T cells after haplo-HSCT was not associated with cGVHD, fungal infection, EBV infection, and CMV infection, and was also not significantly associated with the prognosis after transplantation.
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Antígenos CD28 , Linfócitos T CD8-Positivos , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , Prognóstico , Transplante Haploidêntico , Doença Aguda , Masculino , Feminino , AdultoRESUMO
INTRODUCTION: Multiple myeloma (MM) with extramedullary disease (EMD) is rare in clinical practice, and B cell maturation antigen (BCMA) CAR-T cell therapy is a novel therapy for hematologic malignancies. Very few reports have been published on the effect of CAR-T-cell therapy in MM with EMD. Here, we report a case of MM with extramedullary lesions treated with BCMA CAR-T therapy. CASE PRESENTATION: A 66-year-old female patient presented to our hospital with an enlarged left maxillary gingiva. DIAGNOSIS: Diagnosis of indolent MM stage III (DS staging) and stage III (ISS and R ISS) with extramedullary lesions. INTERVENTION: The patient underwent a clinical trial of humanized anti-BCMA CAR T cell therapy. RESULTS: Symptoms improved; left gingival hyperplasia and swelling resolved; left buccal mass resolved; and neck and submandibular masses resolved. Pathological examination of the exfoliated masses showed necrotic tissue. CONCLUSION: MM with extramedullary lesions often has limited treatment options, and traditional chemotherapy methods are ineffective; however, BCMA CAR-T cell therapy can significantly improve the symptoms of extramedullary lesions in MM.
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Antígeno de Maturação de Linfócitos B , Imunoterapia Adotiva , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Feminino , Idoso , Imunoterapia Adotiva/métodosRESUMO
Dynamic transposition of transposable elements (TEs) in fungal pathogens has significant impact on genome stability, gene expression, and virulence to the host. In Magnaporthe oryzae, genome plasticity resulting from TE insertion is a major driving force leading to the rapid evolution and diversification of this fungus. Despite their importance in M. oryzae population evolution and divergence, our understanding of TEs in this context remains limited. Here, we conducted a genome-wide analysis of TE transposition dynamics in the 11 most abundant TE families in M. oryzae populations. Our results show that these TEs have specifically expanded in recently isolated M. oryzae rice populations, with the presence/absence polymorphism of TE insertions highly concordant with population divergence on Geng/Japonica and Xian/Indica rice cultivars. Notably, the genes targeted by clade-specific TEs showed clade-specific expression patterns and are involved in the pathogenic process, suggesting a transcriptional regulation of TEs on targeted genes. Our study provides a comprehensive analysis of TEs in M. oryzae populations and demonstrates a crucial role of recent TE bursts in adaptive evolution and diversification of the M. oryzae rice-infecting lineage. IMPORTANCE: Magnaporthe oryzae is the causal agent of the destructive blast disease, which caused massive loss of yield annually worldwide. The fungus diverged into distinct clades during adaptation toward the two rice subspecies, Xian/Indica and Geng/Japonica. Although the role of TEs in the adaptive evolution was well established, mechanisms underlying how TEs promote the population divergence of M. oryzae remain largely unknown. In this study, we reported that TEs shape the population divergence of M. oryzae by differentially regulating gene expression between Xian/Indica-infecting and Geng/Japonica-infecting populations. Our results revealed a TE insertion-mediated gene expression adaption that led to the divergence of M. oryzae population infecting different rice subspecies.
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Elementos de DNA Transponíveis , Evolução Molecular , Genoma Fúngico , Oryza , Doenças das Plantas , Elementos de DNA Transponíveis/genética , Oryza/microbiologia , Doenças das Plantas/microbiologia , Virulência/genética , Variação Genética , Ascomicetos/genética , Ascomicetos/classificação , Ascomicetos/patogenicidade , Magnaporthe/genética , Magnaporthe/patogenicidade , Magnaporthe/classificaçãoRESUMO
The new product development (NPD) activities of enterprises serve as a critical source of competitiveness. To effectively harness the opportunities presented by digital transformation and enhance the performance of NPD in organizations amidst the digital revolution is an area of concern that warrants attention. In this context, we conducted research using data from the annual reports of 35 listed mainboard enterprises in 2021. This research used the resource arrangement theory and the resource-structure-capability research framework. In addition, we utilized the quantitative comparative analysis (QCA) method to investigate how digital transformation capability, R&D investment capability, and heterogeneity synergies impact the performance of NPD. The findings indicate that: (1) Four distinct paths (i.e., digital innovation-driven, large-scale multi-talent, mature and robust, and digital start-up) drive improvements in NPD performance. Notably, there exists an asymmetric causal relationship between these four paths and the performance; (2) Digital transformation capability, firm R&D investment, and firm heterogeneity all contribute to enhancing NPD performance. However, they do not individually guarantee high performance. A synergistic effect of at least two factors is required to yield notable NPD performance; (3) Enterprise heterogeneity plays a pivotal role. Companies with different characteristics must opt for distinct digital transformation paths to improve their NPD performance; (4) In the initial stage of digital transformation, enterprises can enhance NPD performance by augmenting their investment in R&D personnel.
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Investimentos em Saúde , ChinaRESUMO
OBJECTIVE: To investigate the clinical features of transplant-associated thrombotic microangiopathy (TA-TMA) and the prognostic value of different prognostic risk models for TA-TMA. METHODS: The clinical characteristics of 32 TA-TMA patients diagnosed at the First Medical Center of the PLA General Hospital from January 2018 to February 2022 in terms of short-term prognosis and influencing factors were retrospectively analyzed. In addition, the risk population composition ratio, treatment response, and overall survival between the BATAP risk model and the TMA index model were compared, as well as the efficacy of two prognostic risk models for predicting death in patients with TA-TMA. RESULTS: Independent risk factors affecting the short-term prognosis of TA-TMA include III-IV aGVHD prior to TA-TMA diagnosis (P=0.001), renal or neurological dysfunction (P=0.006), and Hb<70 g/L (P=0.043). In the TMA index model, treatment response was worst in the high-risk group (P=0.008), while there was no significant difference in treatment response between different risk groups in the BATAP model (P=0.105). In the BATAP model, there was a statistically significant difference in the OS between the three groups of low risk, intermediate risk, and high risk (87.5% vs 61.1% vs 16.7%, χ2ï¼6.7, P=0.014). In the TMA index model, there was a statistically significant difference in the OS between the three groups of low risk, intermediate risk, and high risk (77.8% vs 45.5% vs 0.0%, χ2ï¼7.3, P=0.017). The area under the ROC curve (AUC) of the TMA index model was 0.745 (95%CI: 0.56-0.88, P<0.05), and the AUC of the BATAP model was 0.743 (95%CI: 0.56-0.88, P<0.05), indicating that both prognostic risk models have good predictive value. CONCLUSION: The short-term prognosis of TA-TMA patients might be accurately determined using both the BATAP model and the TMA index model. When predicting the efficacy of TA-TMA in different risk groups, the TMA index model may perform better than the BATAP model.
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Stenotrophomonas maltophilia J2, a highly efficient pyridine-degrading bacterium, was isolated from the aerobic tank of a pesticide-contaminated wastewater treatment plant. The strain J2 demonstrated an impressive pyridine degradation rate of 98.34% ± 0.49% within 72 h, at a pyridine concentration of 1100 mg·L-1, a temperature of 30 °C, a pH of 8.0, and a NaCl concentration of 0.5%. Notably, two new pyridine metabolic intermediates, 1,3-dihydroxyacetone and butyric acid, were discovered, indicating that J2 may degrade pyridine through two distinct metabolic pathways. Furthermore, the immobilized strain J2 was obtained by immobilizing J2 with biochar derived from the stem of Solidago canadensis L. In the pyridine-contaminated wastewater bioremediation experiment, the immobilized strain J2 was able to remove 2000 mg·L-1 pyridine with a 98.66% ± 0.47% degradation rate in 24 h, which was significantly higher than that of the control group (3.17% ± 1.24%), and remained above 90% in subsequent cycles until the 27th cycle. High-throughput sequencing analysis indicated that the J2 +B group had an elevated relative abundance of bacteria and functional genes that could be associated with the degradation of pyridine. The results offer a foundation for the effective use of immobilized strain in the treatment of recalcitrant pyridine-contaminated wastewater.
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Stenotrophomonas maltophilia , Águas Residuárias , Stenotrophomonas maltophilia/metabolismo , Biodegradação Ambiental , Bactérias/metabolismo , Piridinas/metabolismoRESUMO
Donor lymphocyte infusion (DLI) cures relapsed hematologic malignancies after allogeneic hematopoietic stem cell transplantation through the graft-versus-tumor (GVT) effect. Although the important role of magnesium in enhancing immunity has been mentioned in studies, limited clinical data have explored how magnesium affects the efficacy of DLI. Besides, although laboratory data demonstrate that magnesium can enhance CD8+ T cells effector function, whether magnesium regulates the tumor killing effect of peripheral blood mononuclear cells (PBMCs) remains to be explored. Here, for the retrospective study, we collected clinical data of relapsed patients receiving DLI and explored the relationship between different serum magnesium levels and patient outcomes. For in vitro studies, we investigated the effect of magnesium on the cytotoxicity of DLI cells which were PBMCs and preliminarily explored the mechanism. Eighty-one patients were enrolled in this study. It was found that the high post-DLI magnesium level was significantly associated with a higher incidence of complete remission (CR) or partial remission (CR/PR) and a higher possibility of survival. The magnesium level after DLI was an independent risk factor of overall survival. In vitro studies proved that increased magnesium enhanced the cytotoxic function of PBMCs on hematologic malignancies. Besides, magnesium modulated LFA-1 headpiece opening. When blocking the integrin-ligand interaction between LFA-1 and ICAM-1, the regulation effect of magnesium on PBMCs was weakened. Therefore, it was possible that magnesium regulated PBMCs effector function by stimulating LFA-1. These results show that serum magnesium levels affect immunological responses mediated by donor lymphocytes in hematologic malignancies.
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Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Humanos , Magnésio , Linfócitos T CD8-Positivos , Leucócitos Mononucleares , Estudos Retrospectivos , Antígeno-1 Associado à Função Linfocitária , Doença Enxerto-Hospedeiro/etiologia , Recidiva Local de Neoplasia , Transplante de Células-Tronco Hematopoéticas/métodos , Transfusão de Linfócitos/métodosRESUMO
The aim of this study was to examine the relationship between lean body mass (LBM) and the incidence and severity of neutropenia in patients with malignant tumors from Northern China who have received nanoparticle albumin-bound paclitaxel. Twenty-six patients with pathologically confirmed malignant tumors were prospectively included in this study. These 26 patients were divided into Group A (sarcopenia) and Group B (nonsarcopenia). Group A comprised 50% (13/26) of the patients, while Group B comprised the other 50% (13/26). There was no statistically significant difference between both groups in terms of body surface area (P = .052). The incidence of neutropenia in Group A was 76.9% compared to 61.5% in Group B (P = .0673). The incidence of Grade 3 and severe neutropenia was 76.9% versus 61.5% in Groups A and B, respectively (P = .645). These 26 patients were divided into Groups 1 and 2 based on the administered nab-paclitaxel dose per kilogram of LBM, with both groups receiving a body surface area dose of 260 mg/m2 . Group 1 received a nab-paclitaxel dose of 14.19 mg/kg of LBM, whereas Group 2 received 11.37 mg/kg of LBM. In Group 1, the incidence of neutropenia was 71.4%, whereas it was 66.7% in Group 2. Grade 3 or higher neutropenia incidence was 28.6% in Group 1 versus 16.7% in Group 2. Patients with sarcopenia in northern China experienced a higher incidence of severe neutropenia after receiving nab-paclitaxel than patients without sarcopenia. Higher drug dose intensity per unit of LBM may be a contributing factor.
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Paclitaxel Ligado a Albumina , Nanopartículas , Neoplasias , Neutropenia , Sarcopenia , Humanos , Paclitaxel Ligado a Albumina/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Composição Corporal , População do Leste Asiático , Neoplasias/tratamento farmacológico , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Sarcopenia/induzido quimicamenteRESUMO
BACKGROUND Myeloablative chemotherapy supported by autologous stem cell transplantation (ASCT) is an option for primary central nervous system lymphoma (PCNSL) in both the relapse setting and as postremission consolidation, but the level of evidence in this field is still low. MATERIAL AND METHODS We retrospectively analyzed 47 HIV-negative PCNSL patients from 2010 to 2021. To assess the outcomes in patients undergoing ASCT. RESULTS Of the 47 patients, the median age was 51 (range, 21-77) years, and 28 (59.6%) were male. After induction, 33 (70.2%) patients achieved complete remission, and 6 (12.8%) patients achieved partial remission. At a median follow-up of 21.4 months (95% CI 8.86-33.95), the median progression-free survival (PFS) was 23.3 months (95% CI 14.87-31.73), and the 4-year PFS rate was 14.6%. The median overall survival (OS) time was 62.4 months (95% CI 41.93-82.87), and the 4-year OS rate was 71.5%. Among 20 patients who received ASCT (10 consolidation, 10 salvage), the 4-year PFS and 4-year OS rates were 57.3% and 71.2%, respectively. In the multivariate analysis, ASCT therapy (hazard ratio [HR] 0.16, P=0.016) and early remission (HR 0.12, p=0.003) were found to be independent prognostic factors for a longer PFS. Two treatment-related deaths occurred in patients with multiple relapses before ASCT. Pancytopenia and diarrhea were the most common adverse events. CONCLUSIONS ASCT offers potential long-term PFS with good tolerability for patients with PCNSL. Our retrospective cohort adds to the currently available literature and identifies disease status after induction as a significant factor affecting survival.
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Transplante de Células-Tronco Hematopoéticas , Linfoma , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , Transplante Autólogo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva , Linfoma/cirurgia , Sistema Nervoso Central , Transplante de Células-TroncoRESUMO
Determine the association of lean body mass (LBM) on the incidence and severity of peripheral neurotoxicity in cancer patients who received nab-paclitaxel alone or combined with cisplatin or carboplatin. This prospective clinical study examined 32 cancer patients classified into a sarcopenia or non-sarcopenia group according to the Asian L3 vertebra skeletal muscle index (L3-SMI) at Ordos Central Hospital (China) from December 2020-2021, to compare the incidence and severity of neurotoxicity and analizing the relationship between nab-paclitaxel dose per kg LBM and neurotoxicity. There were 18 patients (56.25%) in the sarcopenia group and 14 (43.75%) in the non-sarcopenia group. The incidences of peripheral and severe neurotoxicity were higher in the sarcopenia group (both P < 0.05). Patients in three different body surface area (BSA) groups received the same nab-paclitaxel dose (260 mg/m2 BSA). However, when patients were divided into three groups according to LBM, they received different doses (low-LBM: 15.18 mg/kg LBM, middle-LBM: 12.82 mg/kg LBM, and high-LBM: 11.14 mg/kg LBM). The incidence of grade-C or higher neurotoxicity of these three groups was 61.54% (8/13), 20.00% (1/5), and 11.11% (1/9). Sarcopenia and a higher dose of nab-paclitaxel per kg LBM were associated with peripheral and severe neurotoxicity. Chemotherapy dosing based on body composition may reduce neurotoxicity in patients receiving nab-paclitaxel.Registration number of Clinical Trial: ChiCTR2000040918.
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Neoplasias , Sarcopenia , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Composição Corporal , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Paclitaxel/efeitos adversos , Estudos Prospectivos , Sarcopenia/induzido quimicamente , Sarcopenia/epidemiologiaRESUMO
Amidophosphoribosyltransferase catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate into 5-phosphoribosyl-1-amine in the de novo purine biosynthetic pathway. Herein, we identified and characterized the functions of MoAde4, an orthologue of yeast Ade4 in Magnaporthe oryzae. MoAde4 is a 537-amino acid protein containing GATase_6 and pribosyltran domains. MoADE4 transcripts were highly expressed during the conidiation, early-infection, and late-infection stages of the fungus. Disruption of the MoADE4 gene resulted in ΔMoade4 exhibiting adenine, adenosine, and hypoxanthine auxotrophy on minimal medium. Conidia quantification assays showed that sporulation was significantly reduced in the ΔMoade4 mutant. The conidia of ΔMoade4 could still form appressoria but mostly failed to penetrate the rice cuticle. Pathogenicity tests showed that ΔMoade4 was completely nonpathogenic on rice and barley leaves, which was attributed to restricted infectious hyphal growth within the primary cells. The ΔMoade4 mutant was defective in the induction of strong host immunity. Exogenous adenine partially rescued conidiation, infectious hyphal growth, and the pathogenicity defects of the ΔMoade4 mutant on barley and rice leaves. Taken together, our results demonstrated that purine nucleotide biosynthesis orchestrated by MoAde4 is required for fungal development and pathogenicity in M. oryzae. These findings therefore act as a suitable target for antifungal development against recalcitrant plant fungal pathogens. KEY POINTS: ⢠MoAde4 is crucial for de novo purine nucleotide biosynthesis. ⢠MoAde4 is pivotal for conidiogenesis and appressorium development of M. oryzae. ⢠MoAde4 is involoved in the pathogenicity of M. oryzae.
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Hordeum , Magnaporthe , Oryza , Adenina , Ascomicetos , Proteínas Fúngicas , Regulação Fúngica da Expressão Gênica , Nucleotídeos , Doenças das Plantas , Nucleotídeos de Purina , Esporos Fúngicos , VirulênciaRESUMO
Objective: To review the research progress of reltionship between antitumor drugs and the dynamic changes of the skeletal muscles during treatment phase. Background: Sarcopenia is a common disease in patients with tumors, and it has been agreed that patients with tumors and sarcopenia experience more serious adverse reactions and have a shorter long-term survival after antitumor therapy than patients without sarcopenia. Antitumor drugs whilst beneficial for tumor regression, interferes and synergizes with cancer-induced muscle wasting/sarcopenia, induced myodemia or intramuscular fat and the two conditions often overlap making it difficult to drive conclusions. In recent years, increasing attention has been paid to the dynamic changes in skeletal muscles during antitumor drug therapy. Dynamic changes refer not only measurement skeletal muscle quantity at baseline level, but give more emphasis on the increasing or decreasing level during or end of the whole treatment course. Methods: We retrievaled published English-language original research articles via pubmed, those studies mainly focused on repeated measurements of skeletal muscle index using computed tomography (CT) in cancer patients who received antitumor drug treatment but not received interventions that produced muscle mass change (such as exercise and nutritional interventions). Conclusion: This article will summarize the research progress to date. Most of antineoplastic drug cause skeletal muscle loss during the treatment course, loss of L3 skeletal muscle index is always associated with poor clinical outcomes.
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The functions of ubiquitin-conjugating enzymes (E2) in plant immunity are not well understood. In this study, OsUBC26, a rice ubiquitin-conjugating enzyme, was characterized in the defence against Magnaporthe oryzae. The expression of OsUBC26 was induced by M. oryzae inoculation and methyl jasmonate treatment. Both RNA interference lines and CRISPR/Cas9 null mutants of OsUBC26 reduced rice resistance to M. oryzae. WRKY45 was down-regulated in OsUBC26 null mutants. In vitro E2 activity assay indicated that OsUBC26 is an active ubiquitin-conjugating enzyme. Yeast two-hybrid assays using OsUBC26 as bait identified the RING-type E3 ligase UCIP2 as an interacting protein. Coimmunoprecipitation assays confirmed the interaction between OsUBC26 and UCIP2. The CRISPR/Cas9 mutants of UCIP2 also showed compromised resistance to M. oryzae. Yeast two-hybrid screening using UCIP2 as bait revealed that APIP6 is a binding partner of UCIP2. Moreover, OsUBC26 working with APIP6 ubiquitinateds AvrPiz-t, an avirulence effector of M. oryzae, and OsUBC26 null mutation impaired the proteasome degradation of AvrPiz-t in rice cells. In summary, OsUBC26 plays important roles in rice disease resistance by regulating WRKY45 expression and working with E3 ligases such as APIP6 to counteract the effector protein AvrPiz-t from M. oryzae.
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Resistência à Doença/genética , Magnaporthe , Oryza , Doenças das Plantas , Proteínas de Plantas , Enzimas de Conjugação de Ubiquitina , Ascomicetos , Magnaporthe/patogenicidade , Oryza/enzimologia , Oryza/microbiologia , Doenças das Plantas/microbiologia , Imunidade Vegetal , Proteínas de Plantas/genética , Enzimas de Conjugação de Ubiquitina/genéticaRESUMO
Seawater intrusion not only causes fresh water shortages in coastal areas, but also has a negative impact on regional economic and social development. Global climate change will affect precipitation, sea level, and many other factors, which will in turn affect the simulation and prediction results for seawater intrusion. By combining groundwater numerical simulation technology, an atmospheric circulation model, artificial intelligence methods, and simulation optimization methods, this study coupled a numerical simulation model of seawater intrusion with an optimization model to optimize the groundwater exploitation scheme in the study area under the condition of climate change. As a result, a groundwater exploitation scheme was obtained for a typical study area, which provided a scientific basis and a reference for the rational development of effective groundwater resource solutions. The results of this study can be described as follows. (1) By introducing the theory and method of deep learning from artificial intelligence, the problem of complex nonlinear mapping between the inputs and outputs of a three-dimensional variable-density seawater intrusion numerical simulation model under the condition of limited number of training samples is effectively solved, and the approximation accuracy of the surrogate model with respect to the simulation model is improved. (2) By solving the optimization model, a reasonable groundwater exploitation scheme was obtained, which provided a scientific basis for the rational development and efficient use of groundwater resources in the study area.
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Aprendizado Profundo , Água Subterrânea , Inteligência Artificial , Simulação por Computador , Monitoramento Ambiental , Água do MarRESUMO
OBJECTIVE: The reviewed literature supports a treatment regimen for primary central nervous system lymphoma (PCNSL) that includes induction chemotherapy, followed by one consolidation therapy. High-dose chemotherapy supported by autologous stem-cell transplantation (ASCT) is the most studied option, but its effects are controversial. The aim of this study was to evaluate the efficacy and safety of ASCT for newly diagnosed PCNSL by means of a meta-analysis. METHODS: The PubMed, Embase, and Cochrane Library databases were systematically searched for studies published until May 20, 2021. Included studies were prospective studies of patients with newly diagnosed PCNSL treated with ASCT. The pooled rates and 95% confidence intervals (CIs) were determined for all outcomes. Subgroup analysis was conducted to compare the relative risk (RR) with 95% CIs for the complete remission (CR) rate and the hazard ratios (HRs) with 95% CIs for progression-free survival (PFS) and overall survival (OS). RESULTS: Thirteen prospective studies including 348 patients were analyzed. The pooled CR rate, overall response rate, and relapse rate were 80% (95% CI, 71-88%, I2 = 67.06%, p = 0.00), 95% (95% CI, 87-100%, I2 = 73.65%, p= 0.00), and 19% (95% CI, 15-24%, I2 = 76.18%, p = 0.00), respectively. The pooled 2- and 5-year PFS and OS rates were 74% (95% CI, 68-80%, I2 = 3.90%), 65% (95% CI, 51-77%, I2 = 74.61%), 80% (95% CI, 72-88%, I2 = 57.54%), and 69% (95% CI, 53-83%, I2 = 83.89%), respectively. Hematological toxicity and infections were more common adverse events above grade 3. The pooled treatment-related mortality was 3% (95% CI, 1-6%, I2 = 28.18%, p = 0.16). In the group analysis of ASCT compared with whole-brain radiotherapy, there were no significant differences in the CR rate (RR, 1.00, 95% CI, 0.88-1.14, p = 0.971), relapse rate (RR, 0.44, 95% CI, 0.06-3.10, p = 0.408), PFS (HR, 1.28, 95% CI, 0.81-2.01, p = 0.29), or OS (HR, 1.62, 95% CI, 0.97-2.69, p = 0.06). Cognitive functions were preserved or improved after ASCT. CONCLUSIONS: ASCT is a feasible approach for consolidation with good tolerability for newly diagnosed PCNSL patients. High-quality randomized controlled trials are still needed to confirm the effects of ASCT. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42021268422.
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During the infection and colonization process, the rice blast fungus Magnaporthe oryzae faces various challenges from hostile environment, such as nutrient limitation and carbon stress, while carbon catabolite repression (CCR) mechanism would facilitate the fungus to shrewdly and efficiently utilize carbon nutrients under fickle nutritional conditions since it ensures the preferential utilization of most preferred carbon sources through repressing the expression of enzymes required for the utilization of less preferred carbon sources. Researches on M. oryzae CCR have made some progress, however the involved regulation mechanism is still largely obscured, especially, little is known about the key carbon catabolite repressor CreA. Here we identified and characterized the biological functions of the CreA homolog MoCreA in M. oryzae. MoCreA is constitutively expressed throughout all the life stages of the fungus, and it can shuttle between nucleus and cytoplasm which is induced by glucose. Following functional analyses of MoCreA suggested that it was required for the vegetative growth, conidiation, appressorium formation and pathogenicity of M. oryzae. Moreover, comparative transcriptomic analysis revealed that disruption of MoCreA resulted in the extensive gene expression variations, including a large number of carbon metabolism enzymes, transcription factors and pathogenicity-related genes. Taken together, our results demonstrated that, as a key regulator of CCR, MoCreA plays a vital role in precise regulation of the asexual development and pathogenicity of the rice blast fungus.
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Ascomicetos/genética , Repressão Catabólica/genética , Reprodução Assexuada/genética , Fatores de Transcrição/genética , Ascomicetos/patogenicidade , Carbono/metabolismo , Citoplasma/genética , Proteínas Fúngicas , Glucose/metabolismo , Oryza/genética , Oryza/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Esporos Fúngicos/genética , Esporos Fúngicos/patogenicidade , Ureo-Hidrolases/genética , Virulência/genéticaRESUMO
BACKGROUND: Secondary central nervous system lymphoma (SCNSL) is defined as secondary central nervous system (CNS) involvement in patients with systemic lymphoma. It is considered a profoundly adverse complication with inferior clinical outcome. Parenchymal involvement in the CNS in aggressive B-cell lymphoma is not frequently seen and remains a diagnostic dilemma. METHODS: In our study, we retrospectively analyzed the clinical and magnetic resonance imaging (MRI) features of 26 parenchymal SCNSL patients. In addition, we compared MRI features of SCNSL and primary CNS lymphoma (PCNSL) patients after 1:1 propensity score matching. Also we presented two SCNSL cases with atypical MRI appearance. RESULTS: Among SCNSL patients, the median CNS relapse time was 3 months, and multiple lesions were found in 76.9% of the cases. In PCNSL, this percentage was 42.3% (p = 0.011). None of the SCNSL patients and 23.1% of the PCNSL patients had solitary infratentorial lesions (p = 0.003). CONCLUSIONS: The majority of parenchymal involvement occurred within the first year of systemic lymphoma, in which mostly cases presenting with multiple and supratentorial locations, unlike what was found in PCNSL.
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Neoplasias do Sistema Nervoso Central , Linfoma de Células B/patologia , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Neoplasias do Sistema Nervoso Central/epidemiologia , Neoplasias do Sistema Nervoso Central/secundário , China , Humanos , Imageamento por Ressonância Magnética , Estudos RetrospectivosRESUMO
When using a simulation model to study seawater intrusion (SI), uncertainty in the parameters directly affects the results. The impact of the rise in sea levels due to global warming on SI cannot be ignored. In this paper, the Monte Carlo method is used to analyze the uncertainty in modeling SI. To reduce the computational cost of the repeated invocation of the simulation model as well as time, a surrogate model is established using a radial basis function (RBF)-based neural network method. To enhance the accuracy of the substitution model, input samples are sampled using the Latin hypercube sampling (LHS) method. The results of uncertainty analysis had a high reference value and show the following: (1) The surrogate model created using the RBF method can significantly reduce computational cost and save at least 95% of the time needed for the repeated invocation of the simulation model while maintaining high accuracy. (2) Uncertainty in the parameters and the magnitude of the rise in sea levels have a significant impact on SI. The results of prediction were thus highly uncertain. In practice, it is necessary to quantify uncertainty to provide more intuitive predictions.
Assuntos
Método de Monte Carlo , Modelos Teóricos , Água do Mar , IncertezaRESUMO
The optimization model is presently used for the identification of pollution sources and it is based on non-linear programming optimization. The decision variables in this model are continuous, resulting in a weak recognition of integer variables including pollution source location. In addition, as the number of pollution sources increase, so the calculated load increases exponentially and accuracy decreases. Compared with previous studies, this study makes a series of improvements by adopting a 0-1 mixed integer nonlinear programming optimization model to enable the simultaneous identification of both location (integer variable) and the release intensity (continuous variable) of the pollution source. One of the constraints in the optimization model is a simulation component which requires thousands of calls during the calculation process and therefore requires considerable computational load. To avoid this problem, the Kriging surrogate model is established in this study to reduce computational load, while at the same time ensuring the accuracy of the simulation results. The identification result is solved using a genetic algorithm (GA) and represents the real location of the pollution source, while release intensities are close to actual ones with small relative errors. The Kriging surrogate model is based on a 0-1 mixed integer nonlinear programming optimization model and can simultaneously identify both the location and the release intensity of the pollution source with a high degree of accuracy and by using short computational times.