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1.
Protein Sci ; 33(10): e5131, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39290110

RESUMO

DNA methyltransferase 3B (DNMT3B) plays a crucial role in DNA methylation during mammalian development. Mutations in DNMT3B are associated with human genetic diseases, particularly immunodeficiency, centromere instability, facial anomalies (ICF) syndrome. Although ICF syndrome-related missense mutations in the DNMT3B have been identified, their precise impact on protein structure and function remains inadequately explored. Here, we delve into the impact of four ICF syndrome-linked mutations situated in the DNMT3B dimeric interface (H814R, D817G, V818M, and R823G), revealing that each of these mutations compromises DNA-binding and methyltransferase activities to varying degrees. We further show that H814R, D817G, and V818M mutations severely disrupt the proper assembly of DNMT3B homodimer, whereas R823G does not. We also determined the first crystal structure of the methyltransferase domain of DNMT3B-DNMT3L tetrameric complex hosting the R823G mutation showing that the R823G mutant displays diminished hydrogen bonding interactions around T775, K777, G823, and Q827 in the protein-DNA interface, resulting in reduced DNA-binding affinity and a shift in sequence preference of +1 to +3 flanking positions. Altogether, our study uncovers a wide array of fundamental defects triggered by DNMT3B mutations, including the disassembly of DNMT3B dimers, reduced DNA-binding capacity, and alterations in flanking sequence preferences, leading to aberrant DNA hypomethylation and ICF syndrome.


Assuntos
DNA (Citosina-5-)-Metiltransferases , Metilação de DNA , DNA Metiltransferase 3B , Doenças da Imunodeficiência Primária , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/química , DNA (Citosina-5-)-Metiltransferases/metabolismo , Humanos , Doenças da Imunodeficiência Primária/genética , Síndromes de Imunodeficiência/genética , Modelos Moleculares , Mutação de Sentido Incorreto , Face/anormalidades
2.
Theor Appl Genet ; 137(7): 154, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856926

RESUMO

KEY MESSAGE: Our findings highlight a valuable breeding resource, demonstrating the potential to concurrently enhance grain shape, thermotolerance, and alkaline tolerance by manipulating Gγ protein in rice. Temperate Geng/Japonica (GJ) rice yields have improved significantly, bolstering global food security. However, GJ rice breeding faces challenges, including enhancing grain quality, ensuring stable yields at warmer temperatures, and utilizing alkaline land. In this study, we employed CRISPR/Cas9 gene-editing technology to knock out the GS3 locus in seven elite GJ varieties with superior yield performance. Yield component measurements revealed that GS3 knockout mutants consistently enhanced grain length and reduced plant height in diverse genetic backgrounds. The impact of GS3 on the grain number per panicle and setting rate depended on the genetic background. GS3 knockout did not affect milling quality and minimally altered protein and amylose content but notably influenced chalkiness-related traits. GS3 knockout indiscriminately improved heat and alkali stress tolerance in the GJ varieties studied. Transcriptome analysis indicated differential gene expression between the GS3 mutants and their wild-type counterparts, enriched in biological processes related to photosynthesis, photosystem II stabilization, and pathways associated with photosynthesis and cutin, suberine, and wax biosynthesis. Our findings highlight GS3 as a breeding resource for concurrently improving grain shape, thermotolerance, and alkaline tolerance through Gγ protein manipulation in rice.


Assuntos
Grão Comestível , Oryza , Melhoramento Vegetal , Proteínas de Plantas , Termotolerância , Álcalis , Sistemas CRISPR-Cas , Grão Comestível/genética , Grão Comestível/crescimento & desenvolvimento , Edição de Genes , Regulação da Expressão Gênica de Plantas , Oryza/genética , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Fenótipo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Termotolerância/genética
3.
Heliyon ; 10(6): e28346, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38533035

RESUMO

Collective emotions and actions represent foundational constructs in social psychology, significantly influencing societal dynamics and responses. Within this framework, the Self-Other Overlap (SOO) - wherein individuals perceive minimal distinction between their own and others' identities - has been identified as an impactful factor at the interpersonal level. However, the extrapolation of SOO's implications at the collective, group level remains an underexplored domain in contemporary research. In addressing this lacuna, the present research endeavors to elucidate the multifaceted implications of SOO on group emotions and actions, contextualized within societal challenges such as "food hygiene problems". Utilizing validated instruments including the Self-Other Overlap Scale, Group-Based Anger Scale, Collective Action Tendency Scale, and Group Efficacy Scale for Coping Situations, this study adopts a tripartite situational experiment, engaging a collective sample of 359 participants, systematically recruited via the Credamo smart research platform to ensure representativeness. Study 1 examined the potential influence of variable SOO degrees on Group-Based Anger (GA) and Collective Action Tendency (CAT). Study 2 further refined the exploration, discerning the differential impacts of SOO targets on GA and CAT. Conclusively, Study 3 sought to ascertain the potential moderating role of Group Efficacy (GE) within the SOO-GA-CAT relationship. The empirical findings yielded several salient insights: notably, an augmentation in SOO levels corresponded with an amplification of GA and CAT. Furthermore, a delineation in SOO targets, specifically from external to ingroup entities, manifested in a pronounced augmentation of GA and CAT. Intriguingly, while elevated SOO predisposed heightened CAT, the modulatory effect of GE on CAT manifested predominantly in lower SOO contexts. In summation, the present study underscores the pivotal role of SOO magnitude and orientation as determinants of GA and CAT. The nuanced interplay between SOO degree and GE, particularly vis-à-vis CAT, provides a fresh scholarly perspective, contributing to the enriched understanding of group dynamics and collective behavioral paradigms.

4.
IEEE J Biomed Health Inform ; 28(5): 2979-2990, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38457317

RESUMO

Accurate medical image segmentation is an essential part of the medical image analysis process that provides detailed quantitative metrics. In recent years, extensions of classical networks such as UNet have achieved state-of-the-art performance on medical image segmentation tasks. However, the high model complexity of these networks limits their applicability to devices with constrained computational resources. To alleviate this problem, we propose a shallow hierarchical Transformer for medical image segmentation, called SHFormer. By decreasing the number of transformer blocks utilized, the model complexity of SHFormer can be reduced to an acceptable level. To improve the learned attention while keeping the structure lightweight, we propose a spatial-channel connection module. This module separately learns attention in the spatial and channel dimensions of the feature while interconnecting them to produce more focused attention. To keep the decoder lightweight, the MLP-D module is proposed to progressively fuse multi-scale features in which channels are aligned using Multi-Layer Perceptron (MLP) and spatial information is fused by convolutional blocks. We first validated the performance of SHFormer on the ISIC-2018 dataset. Compared to the latest network, SHFormer exhibits comparable performance with 15 times fewer parameters, 30 times lower computational complexity and 5 times higher inference efficiency. To test the generalizability of SHFormer, we introduced the polyp dataset for additional testing. SHFormer achieves comparable segmentation accuracy to the latest network while having lower computational overhead.


Assuntos
Algoritmos , Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Humanos , Processamento de Imagem Assistida por Computador/métodos , Bases de Dados Factuais
5.
Heliyon ; 10(4): e26229, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38420423

RESUMO

Infrared ship detection is of great significance due to its broad applicability in maritime surveillance, traffic safety and security. Multiple infrared sensors with different spectral sensitivity provide enhanced sensing capabilities, facilitating ship detection in complex environments. Nevertheless, current researches lack discussion and exploration of infrared imagers in different spectral ranges for marine objects detection. Furthermore, for unmanned marine vehicles (UMVs), e.g., unmanned surface vehicles (USVs) and unmanned ship (USs), detection and perception are usually performed in embedded devices with limited memory and computation resource, which makes traditional convolutional neural network (CNN)-based detection methods struggle to leverage their advantages. Aimed at the task of sea surface object detection on USVs, this paper provides lightweight CNNs with high inference speed that can be deployed on embedded devices. It also discusses the advantages and disadvantages of using different sensors in marine object detection, providing a reference for the perception and decision-making modules of USVs. The proposed method can detect ships in short-wave infrared (SWIR), long-wave infrared (LWIR) and fused images with high-performance and high-inference speed on an embedded device. Specifically, the backbone is built from bottleneck depth-separable convolution with residuals. Generating redundant feature maps by using cheap linear operation in neck and head networks. The learning and representation capacities of the network are promoted by introducing the channel and spatial attention, redesigning the sizes of anchor boxes. Comparative experiments are conducted on the infrared ship dataset that we have released which contains SWIR, LWIR and the fused images. The results indicate that the proposed method can achieve high accuracy but with fewer parameters, and the inference speed is nearly 60 frames per second (FPS) on an embedded device.

6.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1029110

RESUMO

Objective:To investigate the risk factors of atrial fibrillation (AF) in patients with typical atrial flutter after radiofrequency ablation.Methods:This study was a case-control study. The clinical data of 120 patients with typical atrial flutter who underwent radiofrequency ablation in Xingtai People′s Hospital from January 2017 to January 2021 were retrospectively analyzed. Patients were followed up every 3-6 months for a period of 2 years, and AF occurred in 30 patients (25.0%). The risk factors of AF were analyzed with univariate and multivariate logistic regressions.Results:The mean age of patients was (62.0±6.5) years and 64(53.3%) were males. No patients in the two groups had complications such as cardiac tamponade, pulmonary embolism and cerebral infarction after radiofrequency ablation. Compared with non-AF patients, patients in AF group had older age and higher CHA 2DS 2-VASC score ( P<0.001). Multivariate regression analysis showed that age ( HR=1.09, 95% CI:1.01-1.17) and CHA 2DS 2-VASC score ( HR=3.84, 95% CI:1.87-7.89) were independent risk factors for the occurrence of atrial fibrillation after radiofrequency ablation in patients with atrial flutter. Conclusion:After radiofrequency ablation of typical atrial flutter, nearly 25% of patients will relapse into AF, old age and higher CHA 2DS 2-VASC score increase the risk of AF recurrent.

7.
Infect Dis Ther ; 12(8): 2087-2102, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37486556

RESUMO

INTRODUCTION: Azvudine and nirmatrelvir-ritonavir are more extensively used to treat COVID-19 in China due to their earlier approval by the National Medical Products Administration. However, there has been a scarcity of research directly comparing the clinical outcomes between azvudine and nirmatrelvir-ritonavir till now. We aimed to make a head-to-head comparison of the efficacy and safety of azvudine or nirmatrelvir-ritonavir in hospitalized patients with COVID-19 in China. METHODS: This retrospective cohort study was conducted using data collected from Tongde Hospital of Zhejiang Province between December 2022 and January 2023. All-cause mortality, risk of progressing to a critical condition, proportion with nucleic-acid negative conversion (PNANC), time to first nucleic-acid negative conversion (TFNANC), length of hospital stay and incidence of adverse events were systematically assessed as outcomes. Multi-model regression analysis, propensity-score-matching analysis, subgroup analysis and several sensitivity analyses were applied to compare these outcomes. RESULTS: This study included a total of 1571 hospitalized patients with COVID-19, among whom 272 received nirmatrelvir-ritonavir and 156 received azvudine. We found no significant differences in all-cause mortality (HR 1.41; 95% CI 0.56-3.56; P = 0.471), risk of progressing to critical COVID-19 (HR 1.67; 95% CI 0.78-3.60; P = 0.189), PNANC (HR 0.87; 95% CI 0.69-1.09; P = 0.220), length of stay (ß - 0.82; 95% CI - 2.78 to 1.15; P = 0.414) and adverse event rate (3.21% vs. 4.41%, P = 0.538) between the two groups, although azvudine was slightly less effective than nirmatrelvir-ritonavir. Meanwhile, the azvudine group exhibited a significantly longer TFNANC (ß 2.53; 95% CI 0.76-4.29; P = 0.005) than the nirmatrelvir-ritonavir group. Results were similar for propensity-score matching and multiple sensitivity analyses. CONCLUSION: Azvudine probably possessed comparable efficacy and safety to nirmatrelvir-ritonavir, although it was less effective than nirmatrelvir-ritonavir for some outcomes.

8.
Front Psychol ; 14: 1071985, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37292512

RESUMO

Personality is considered as the internal factor that defines a person's behavior. Therefore, providing adaptive features and personalized support in online learning by considering learners' personalities can improve their learning experiences and outcomes. In this context, several research studies have investigated the impact of personality differences in online learning. However, little is known about how personality differences affect learners' behavior while learning. To fill this gap, this study applies a lag sequential analysis (LSA) approach to understand learners' navigational behavior patterns in an online three-months course of 65 learners based on their personalities. In this context, the five factor model (FFM) model was used to identify learners' personalities. The findings revealed that learners with different personalities use different strategies to learn and navigate within the course. For instance, learners high in extraversion tend to be extrinsically motivated. They therefore significantly navigated between viewing the course module and their personal achievements. The findings of this study can contribute to the adaptive learning field by providing insights about which personalization features can help learners with different personalities. The findings can also contribute to the field of automatic modeling of personality by providing information about differences in navigational behavior based on learners' personalities.

9.
ACS Chem Biol ; 18(6): 1335-1350, 2023 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-37188336

RESUMO

Mammalian DNA methyltransferases (DNMTs), including DNMT1, DNMT3A, and DNMT3B, are key DNA methylation enzymes and play important roles in gene expression regulation. Dysregulation of DNMTs is linked to various diseases and carcinogenesis, and therefore except for the two approved anticancer azanucleoside drugs, various non-nucleoside DNMT inhibitors have been identified and reported. However, the underlying mechanisms for the inhibitory activity of these non-nucleoside inhibitors still remain largely unknown. Here, we systematically tested and compared the inhibition activities of five non-nucleoside inhibitors toward the three human DNMTs. We found that harmine and nanaomycin A blocked the methyltransferase activity of DNMT3A and DNMT3B more efficiently than resveratrol, EGCG, and RG108. We further determined the crystal structure of harmine in complex with the catalytic domain of the DNMT3B-DNMT3L tetramer revealing that harmine binds at the adenine cavity of the SAM-binding pocket in DNMT3B. Our kinetics assays confirm that harmine competes with SAM to competitively inhibit DNMT3B-3L activity with a Ki of 6.6 µM. Cell-based studies further show that harmine treatment inhibits castration-resistant prostate cancer cell (CRPC) proliferation with an IC50 of ∼14 µM. The CPRC cells treated with harmine resulted in reactivating silenced hypermethylated genes compared to the untreated cells, and harmine cooperated with an androgen antagonist, bicalutamide, to effectively inhibit the proliferation of CRPC cells. Our study thus reveals, for the first time, the inhibitory mechanism of harmine on DNMTs and highlights new strategies for developing novel DNMT inhibitors for cancer treatment.


Assuntos
Antineoplásicos , Neoplasias de Próstata Resistentes à Castração , Masculino , Animais , Humanos , Metilação de DNA , Harmina/farmacologia , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Regulação da Expressão Gênica , Transformação Celular Neoplásica/genética , Inibidores Enzimáticos/farmacologia , Antineoplásicos/farmacologia , DNA/metabolismo , Mamíferos/genética , Mamíferos/metabolismo
10.
Heliyon ; 9(3): e14166, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36938466

RESUMO

In this paper, a modified infrared and visible image registration method based on contour feature is proposed. Our method firstly extracts the feature contour and eliminates sparkling waves contour of the sea surface, determines the main direction of the contour based on the contour image, then uses the improved Scale Invariant Feature Transform (SIFT) method as the feature point to construct the descriptor, completes the registration of the two images. 30 sets of infrared and visible-band vessels images were selected for registration experiments. Compared with previous reports, the experimental results showed that the proportion of effective feature points detected by this method can reach 70%, and the average number of effective feature points detected by proposed method can reach 196 in visible band image and 279 in infrared image. The running time was 5.3599s, shortened by 25% compared with previous reports, and the average Root Mean Square Error (RMSE) value was 2.3566, smaller by 75% compared with previous reports. An effective registration method is provided, which can be used for infrared and visible image processing and comprehensive utilization of information in marine scenes.

11.
Educ Inf Technol (Dordr) ; : 1-36, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36643383

RESUMO

Intelligent Tutoring Systems (ITSs) have a great potential to effectively transform teaching and learning. As more efforts have been put on designing and developing ITSs and integrating them within learning and instruction, mixed types of results about the effectiveness of ITS have been reported. Therefore, it is necessary to investigate how ITSs work in real and natural educational contexts and the associated challenges of ITS application and evaluation. Through a systematic literature review method, this study analyzed 40 qualified studies that applied social experiment methods to examine the effectiveness of ITS during 2011-2022. The obtained results highlighted a complicated landscape regarding the effectiveness of ITS in real educational contexts. Specifically, there was an "intelligent" regional gap regarding the distribution of countries where ITS studies using social experiment methods were conducted. Compared to learning performance, relatively less attention was paid to investigating the impact of ITS on non-cognitive factors, process-oriented factors, and social outcomes, calling for more research in this regard. Considering the complexities and challenges existing in real educational fields, there was a lack of scientific rigor in terms of experimental design and data analysis in some of the studies. Based on these findings, suggestions for future study and implications were proposed.

12.
Acta Pharmaceutica Sinica ; (12): 1867-1879, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-978660

RESUMO

By integrating plant metabonomics and target quantitative analysis methods, this study systematically analyzed the differences of chemical constituents in Scutellaria baicalensis leaves from different producing areas in Shanxi, so as to provide theoretical basis for rational and effective utilization of Scutellaria baicalensis leaves. Based on the idea of plant metabonomics, the liquid quality of 53 batches of Scutellaria baicalensis leaves from 8 different producing areas in Shanxi was analyzed by UPLC-QTOF-MS, and the collected data were imported into SIMCA 14.1 software for multivariate statistical analysis to screen the different chemical constituents among different habitats in Shanxi. Meanwhile, a method for simultaneous determination of 7 flavonoids and 3 organic acids in Scutellaria baicalensis leaves was optimized and established to quantitatively analyze the differences of chemical components in Scutellaria baicalensis leaves from different producing areas in Shanxi. The results of plant metabonomics showed that there were differences in the chemical composition of Scutellaria baicalensis leaves in northern Shanxi (Datong, Xinzhou), Jinzhong (Yangquan, Luliang) and southern Shanxi (Changzhi, Yuncheng, Jincheng, Linfen): there were 14 significant differences in chemical composition between northern Shanxi and Jinzhong; there were 18 significant differences in chemical constituents between southern Shanxi and central Shanxi. There were 15 significant differences in chemical constituents between northern Shanxi and southern Shanxi. Among them, scutellarin and isocarthamidin-7-O-glucuronide were the common differences among the three regions, and the content of scutellarin was the highest in southern Shanxi and the lowest in northern Shanxi. The content of isocarthamidin-7-O-glucuronide was the highest in Jinzhong area and the lowest in northern Shanxi area. Quantitative analysis further confirmed that the average contents of apigenin, naringenin and citric acid were the highest in northern Shanxi, scutellarin, caffeic acid, apigenin-7-O-glucuronide, malic acid and wogonoside were the highest in southern Shanxi, and wogonoside and baicalin were the highest in central Shanxi. This study is of great significance to the quality control of Scutellaria baicalensis leaf resources, and provides theoretical basis for rational and effective utilization of Scutellaria baicalensis leaf resources.

13.
Chinese Journal of Hematology ; (12): 284-288, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-984616

RESUMO

Objective: To determine the optimal cutoff value of Epstein-Barr virus (EBV) DNA load that can assist in the diagnosis of post-transplant lymphoproliferative disease (PTLD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The data of patients with EBV infection after haplo-HSCT from January to December 2016 were retrospectively analyzed. Through constructing the receiver operating characteristic (ROC) curve and calculating the Youden index to determine the cutoff value of EBV-DNA load and its duration of diagnostic significance for PTLD. Results: A total of 94 patients were included, of whom 20 (21.3% ) developed PTLD, with a median onset time of 56 (40-309) d after transplantation. The median EBV value at the time of diagnosis of PTLD was 70,400 (1,710-1,370,000) copies/ml, and the median duration of EBV viremia was 23.5 (4-490) d. Binary logistic regression was used to analyze the peak EBV-DNA load (the EBV-DNA load at the time of diagnosis in the PTLD group) and duration of EBV viremia between the PTLD and non-PTLD groups. The results showed that the difference between the two groups was statistically significant (P=0.018 and P=0.001) . The ROC curve was constructed to calculate the Youden index, and it was concluded that the EBV-DNA load ≥ 41 850 copies/ml after allogeneic hematopoietic stem cell transplantation had diagnostic significance for PTLD (AUC=0.847) , and the sensitivity and specificity were 0.611 and 0.932, respectively. The duration of EBV viremia of ≥20.5 d had diagnostic significance for PTLD (AUC=0.833) , with a sensitivity and specificity of 0.778 and 0.795, respectively. Conclusion: Dynamic monitoring of EBV load in high-risk patients with PTLD after haplo-HSCT and attention to its duration have important clinical significance, which can help clinically predict the occurrence of PTLD in advance and take early intervention measures.


Assuntos
Humanos , Infecções por Vírus Epstein-Barr/diagnóstico , Herpesvirus Humano 4/genética , Estudos Retrospectivos , Viremia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos Linfoproliferativos/etiologia , DNA Viral , Carga Viral
14.
Chinese Journal of Hematology ; (12): 458-464, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-984644

RESUMO

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide Aguda/terapia , Recidiva , Doença Enxerto-Hospedeiro/etiologia , Doença Crônica
15.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-985993

RESUMO

Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ2=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ2=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.


Assuntos
Humanos , Citomegalovirus , Estudos Retrospectivos , Estudos de Coortes , Estudos Prospectivos , Infecções por Citomegalovirus/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/prevenção & controle , Recidiva , Antivirais/uso terapêutico
16.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1029051

RESUMO

Objective:To compare the efficacy of high density grid mapping catheter (HD-Grid) and circular mapping catheter in the ablation of paroxysmal atrial fibrillation.Methods:Patients with paroxysmal atrial fibrillation undergoing radiofrequency ablation in Xingtai People′s Hospital from March 2020 to March 2021 were randomly divided into the HD-Grid group and the circular mapping catheter group. The baseline data, operation time, X-ray exposure time, pulmonary vein isolation time, recovery of pulmonary vein conduction, the number of recovery sites, and perioperative complications were compared between the two groups. The patients were followed up at 1, 3, 6 and 12 months after operation, and a continuous electrocardiogram was performed to evaluate recurrence of atrial fibrillation.Results:Sixty patients were enrolled in the study with 30 cases in each group, including 33 males and 27 females with an average age of 63.0 (57.0, 70.3) years. There were no significant differences in age, gender ratio, comorbidity proportion, CHADS 2-VASC score, history of atrial fibrillation, B-type natriuretic peptide level, and left atrial diameter between the two groups (all P>0.05). The operation time of the HD-Grid group was longer than that of the circular mapping catheter group ((136.6±7.7) minutes vs. (127.5±7.7) minutes, P<0.001). During the observation period, 8 cases (26.67%) with pulmonary venous conduction recovery were identified in the HD-Grid group, which was higher than that in the circular mapping catheter group (2 cases(6.67%)) ( P=0.038). Eighteen (60.00%) pulmonary vein reconnection sites were identified in the HD-Grid group, which were more than that in the circular mapping catheter group (2 sites(6.67%), P=0.013). There was no significant difference in X-ray exposure time and pulmonary vein isolation time between the two groups (both P>0.05). There was no significant difference in the proportion of patients taking anticoagulant drugs and antiarrhythmic drugs during the perioperative period between the two groups (both P>0.05). No serious complications such as cardiac tamponade, phrenic nerve injury, pulmonary embolism, cerebral infarction and death occurred in both groups. During the follow-up period, 1 patient (3.33%) in the HD-Grid group had recurrence of atrial fibrillation, while 5 patients (16.67%) in the circular mapping catheter group had recurrence of atrial fibrillation, but there was no significant difference between the two groups ( P=0.197). Conclusions:HD-Grid for radiofrequency ablation of paroxysmal atrial fibrillation improves the identification rate of pulmonary vein potentials and pulmonary vein reconnection sites, and it may reduce the recurrence rate of atrial fibrillation. Although the operation time was prolonged, it would not increase the risk of perioperative complications.

17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1029826

RESUMO

Objective:To compare results of four glycosylated hemoglobin A1c (HbA1c) detection methods and to evaluate the uncertainty of HbA1C results in clinical laboratory, and to provide method for clinical laboratory on the evaluation of uncertainty.Methods:According to the four uncertainty evaluation methods, which were recommended by "CNAS-TRL-001, the evaluation and expression of measurement uncertainty in medical laboratory", the relative and absolute uncertainty of low, medium and high HbA1c in 33 clinical laboratories measured in 2019 and 35 clinical laboratories measured in 2020 was evaluated by more than 6 months of internal quality control (IQC) data, trueness verification and external quality assessment (EQA) data. The four uncertainty evaluation methods were: IQC data and trueness verification data (method 1), only trueness verification data (method 2), IQC and EQA data (method 3) and only EQA data (method 4). The related statistical methods used in this analysis were Friedman and Wilcoxon signed rank test.Results:For method 1, the median range of relative and absolute uncertainty of low, medium and high HbA1c detection in 2019 and 2020 ranged from 4.21% to 9.24% and from 0.27% to 0.64%, respectively. Compared to method 1, the relative and absolute uncertainties obtained by method 2 were smaller, and the differences were statistically significant ( P<0.016 7, P<0.05). Compared to method 1, the relative uncertainties obtained by method 3 and method 4 were smaller, except for the high concentration of HbA1c level in 2020. Among the 6 pairs of comparisons (low, medium and high HbA1c in 2019 and 2020), there were 3 pairs (high HbA1c in 2019, low and medium HbA1c in 2020) and 2 pairs (low and high HbA1c in 2020) of differences with statistical significance (all P<0.016 7). Conclusion:The uncertainty evaluation of HbA1c detection in clinical laboratory should be evaluated based on IQC and trueness verification data.

18.
Acta Pharmaceutica Sinica ; (12): 3428-3438, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-999073

RESUMO

The AP2/ERF gene family is one of the largest transcription factor families in the plant kingdom, and plays an important role in response to biological and abiotic stresses, plant hormone responses, and plant growth and development. In this study, the AP2/ERF family of Panax notoginseng was identified by bioinformatics methods, and the physicochemical properties, structure, phylogenetic relationship, expression pattern and function of PnDREB4 gene of the family were analyzed. The results showed that 140 AP2/ERF family members were identified in P. notoginseng, which were divided into DREB, ERF, AP2, RAV and Sololit subgroups. The physicochemical properties and motifs of proteins were similar among the subgroups. There were 34 differentially expressed genes in the AP2/ERF family of Fusarium oxysporum infected P. notoginseng plants, and 19 genes were up-regulated. The expression level of PnDREB84 was up-regulated with the extension of Fusarium oxysporum infection time in the range of 0-96 h. The content of ABA and SA in P. notoginseng plants overexpressing PnDREB84 gene increased after 4 ℃ stress. The results showed that PnDREB84 gene plays a dual regulatory role in the process of biological stress and abiotic stress. PnDREB84 gene can be used as a potential molecular marker for the breeding of new varieties of P. notoginseng. The identification of AP2/ERF transcription factor and function analysis of PnDREB84 gene of P. notoginseng provided data support for the analysis of stress resistance mechanism of P. notoginseng and the breeding of new varieties.

19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1004694

RESUMO

【Objective】 To investigate the preparation quality and clinical application effect of pooled platelets with leukocytes reduced. 【Methods】 The quality and clinical effect of the buffy-coated method prepared pooled platelets leukocytes reduced (experimental group, n=40) and apheresis platelets leukocytes reduced (control group, n=40) were compared. 【Results】 The platelet volume (mL), platelet count (×1011), red blood cell contamination (×108) and residual white blood cell (×106) of the experimental group and control group were 278.90±7.92 vs 276.52±8.01, 2.66±0.09 vs 2.66±0.83, 0.54±0.42 vs 0.83±0.84, 0.29±0.54 vs 0.27±0.51, respectively, with no significant difference. The results of bacterial culture were negative, all met the requirements of relevant national standards. In addition, the CCI (×103, 24 h) and PPR (%) were 15.11±9.86 vs 14.61±12.55 and 54.23±18.70 vs 61.41±19.09 respectively, with no significant difference, indicating a certain degree of therapeutic effect. 【Conclusion】 The quality and clinical therapeutic effect of pooled platelets leukocytes reduced were consistent with that of apheresis platelets leukocytes reduced.

20.
Chinese Journal of Hematology ; (12): 890-899, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1012253

RESUMO

Objective: To assess the feasibility of using donors with novel coronavirus disease 2019 (COVID-19) for allogeneic hematopoietic stem cell transplantation (allo-HSCT) when there are no other available donors and allo-HSCT cannot be delayed or discontinued. Methods: Seventy-one patients with malignant hematological diseases undergoing allo-HSCT between December 8, 2022, and January 10, 2023, were included. Of these, 16 received grafts from donors with mild COVID-19 (D-COVID(+) group) and 55 received grafts from donors without COVID-19 (D-COVID(-) group). The graft compositions were compared between the two groups. Engraftment, acute graft-versus-host disease (aGVHD), overall survival (OS), and relapse were also evaluated. Results: There were no serious side effects or adverse events in the D-COVID(+) group. The mononuclear cell dose and CD34(+) cell dose were comparable between the two groups, and no additional apheresis was required. There were no significant differences in the lymphocyte, monocyte, and T-cell subset doses between the two groups. The median natural killer cell dose in the D-COVID(+) group was significantly higher than that in the D-COVID(-) group (0.69×10(8)/kg vs. 0.53×10(8)/kg, P=0.031). The median follow-up time was 72 (33-104) days. All patients achieved primary engraftment. The 60-day platelet engraftment rates in the D-COVID(+) and D-COVID(-) groups were 100% and (96.4±0.2) %, respectively (P=0.568). There were no significant differences in neutrophil (P=0.309) and platelet (P=0.544) engraftment times. The cumulative incidence of grade 2-4 aGVHD was (37.5±1.6) % vs. (16.4±0.3) % (P=0.062), and of grade 3-4 aGVHD was 25.0% ±1.3% vs. 9.1% ±0.2% (P=0.095) in the D-COVID(+) and D-COVID(-) groups, respectively. The probabilities of 60-day OS were 100% and 98.1% ±1.8% (P=0.522) in the D-COVID(+) and D-COVID(-) groups, respectively. There was no relapse of primary disease during the study period. Conclusion: When allo-HSCT cannot be delayed or discontinued and no other donor is available, a donor with mild COVID-19 should be considered if tolerable. Larger sample sizes and longer follow-up periods are required to validate these results.


Assuntos
Humanos , COVID-19 , SARS-CoV-2 , Transplante de Células-Tronco Hematopoéticas , Doadores de Tecidos , Doença Enxerto-Hospedeiro
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