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OBJECTIVE: To investigate the status of the midwifery workforce and childbirth services in China and to identify the association between midwife staffing and childbirth outcomes. DESIGN: A descriptive, multicentre cross-sectional survey. SETTING: Maternity hospitals from the eastern, central and western regions of China. PARTICIPANTS: Stratified sampling of maternity hospitals between 1 July and 31 December 2021.The sample hospitals received a package of questionnaires, and the head midwives from the participating hospitals were invited to fill in the questionnaires. RESULTS: A total of 180 hospitals were selected and investigated, staffed with 4159 midwives, 412 obstetric nurses and 1007 obstetricians at the labour and delivery units. The average efficiency index of annual midwifery services was 272 deliveries per midwife. In the sample hospitals, 44.9% of women had a caesarean delivery and 21.4% had an episiotomy. Improved midwife staffing was associated with reduced rates of instrumental vaginal delivery (adjusted ß -0.032, 95% CI -0.115 to -0.012, p<0.05) and episiotomy (adjusted ß -0.171, 95% CI -0.190 to -0.056, p<0.001). CONCLUSION: The rates of childbirth interventions including the overall caesarean section in China and the episiotomy rate, especially in the central region, remain relatively high. Improved midwife staffing was associated with reduced rates of instrumental vaginal delivery and episiotomy, indicating that further investments in the midwifery workforce could produce better childbirth outcomes.
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Cesárea , Parto Obstétrico , Partería , Humanos , China/epidemiología , Estudios Transversales , Femenino , Embarazo , Partería/estadística & datos numéricos , Adulto , Cesárea/estadística & datos numéricos , Parto Obstétrico/estadística & datos numéricos , Resultado del Embarazo/epidemiología , Encuestas y Cuestionarios , Admisión y Programación de Personal/estadística & datos numéricos , Maternidades/estadística & datos numéricos , Episiotomía/estadística & datos numéricos , Servicios de Salud Materna/estadística & datos numéricos , Servicios de Salud Materna/provisión & distribución , Recursos Humanos/estadística & datos numéricosRESUMEN
AIMS: To explore women's and health professionals' views on the development of a midwifery-led mHealth app intervention in antenatal care and their demands for app functionality. DESIGN: Descriptive qualitative research was utilized. METHODS: In total, 15 pregnant or postpartum women were interviewed via in-depth interviews and 10 health professionals including obstetricians, midwives and obstetric nurses were invited to participate in a focus group discussion (FGD). All interviews and the FGD were analysed using qualitative content analysis. RESULTS: Four key themes emerged from the data, including (1) limitations of current maternity care services; (2) potential benefits for mHealth app-based midwifery care; (3) possible challenges for providing midwifery care through mHealth apps and (4) suggestions and needs for developing a midwifery-led mHealth app. Participants agreed on the potential need of developing a midwifery-led mHealth app in antenatal care to increase access to midwifery care services and to meet women's diverse needs. Participants preferred to develop professional, reliable, full-featured and interactive mobile applications. The main functions of midwifery-led mHealth apps included personalized assessment and health education, self-monitoring and feedback, data sharing and interactive functions. Women mentioned that online communication and consultation with midwives could help them receive continuous support outside facilities. Health professionals expressed it would be of great convenience and timeliness to send personalized messages to women and to inform them of healthy lifestyles during pregnancy. The challenges included a shortage of human resources, medico-legal risks associated with mHealth and data security risks. CONCLUSIONS: This study explores the individual views and functional needs of target users and healthcare providers for developing a midwifery-led mHealth app in antenatal care, which will serve as a reference for future application development. IMPACT: Our study has important and practical implications for guiding the development of future midwifery-led mHealth app interventions. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.
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[This corrects the article DOI: 10.1016/j.heliyon.2022.e11190.].
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BACKGROUND: Postnatal period is a critical transitional phase in the lives of mothers and newborn babies. In recent years the importance on promoting a positive experience of care following childbirth is increasingly emphasized. Yet published evidence of the methodological and psychometric quality of instruments to evaluate women's experience of comprehensive postnatal care is still lacking. OBJECTIVE: This study aimed to develop and validate a unique scale (the Chinese version of the Postnatal Care Experience Scale, PCES) to measure women's overall experience of care during postnatal periods. METHODS: The PCES instrument was developed and validated over three phases, including item development, scale development, and scale evaluation. The item pool of the PCES was generated through existing literature and in-depth semi-structured interviews, followed by assessment of content validity and rating of importance and feasibility of items through two-round Delphi surveys. Psychometric properties were examined in a convenience sample of 736 postpartum women. Both exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted to assess the construct validity of the developed PCES. The relationship between the total PCES score and the global item construct was estimated using Pearson product-moment coefficient. Reliability was assessed using Cronbach's alpha and Spearman Brown coefficients. RESULTS: The content validity index of the Chinese version PCES was 0.867. Following item reduction analysis, this instrument consisted of 30 five-point Likert items. The Kaiser-Meyer-Olkin statistic was 0.964 and the chi-square value of the Bartlett spherical test was 11665.399 (P < .001). The scale explained 75.797% of the total variance and consisted of three subscales, including self-management, social support, and facility- and community-based care. The Pearson correlation coefficient between the total PCES score and the global item construct was 0.909. The CFA showed that the 3-factor model had suitable fitness for the data. Cronbach's alpha value and Spearman-Brown Split-half reliability for the total scale were 0.979 and 0.941, respectively. CONCLUSIONS: The newly developed 30-item PCES is a psychometrically reliable and valid instrument that assesses women's overall experience of postnatal care. Future research should aim to use the PCES in various populations to obtain further evidence for its validity and reliability.
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Atención Posnatal , Periodo Posparto , Embarazo , Recién Nacido , Humanos , Femenino , Encuestas y Cuestionarios , Psicometría , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND & AIMS: Clostridioides difficile is a toxin-secreting bacteria that is an urgent antimicrobial resistance threat, with approximately 25% of patients developing recurrent infections. Inflammatory bowel disease (IBD) patients are at increased risk of severe, recurrent C. difficile infection. METHODS: To investigate a role for C. difficile infection in IBD pathogenesis, we collected peripheral blood and stool from 20 each of ulcerative colitis patients, Crohn's disease patients, and healthy control subjects. We used a flow cytometric activation induced marker assay to quantify C. difficile toxin-specific CD4+ T cells and 16S ribosomal RNA sequencing to study microbiome diversity. RESULTS: We found IBD patients had significantly increased levels of C. difficile toxin B-specific CD4+ T cells, but not immunoglobulin G or immunoglobulin A, compared with healthy control subjects. Within antigen-specific CD4+ T cells, T helper type 17 cells and cells expressing the gut homing receptor integrin ß7 were reduced compared with healthy control subjects, similar to our previous study of non-IBD patients with recurrent C. difficile infection. Stool microbiome analysis revealed that gut homing, toxin-specific CD4+ T cells negatively associated with microbial diversity and, along with T helper type 17 cells, positively associated with bacteria enriched in healthy control subjects. CONCLUSIONS: These data suggest that IBD patients, potentially due to underlying intestinal dysbiosis, experience undiagnosed C. difficile infections that result in impaired toxin-specific immunity. This may contribute to the development of inflammatory T cell responses toward commensal bacteria and provide a rationale for C. difficile testing in IBD patients.
Crohn's disease and ulcerative colitis patients with no history of Clostridioides difficile infection had dysregulated T cell immunity to C. difficile toxin B. This was significantly different from healthy control subjects but similar to noninflammatory bowel disease patients with recurrent C. difficile infection.
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Gastric cancer (GC) is the leading cause of cancer-related death worldwide, and reducing its mortality has become an urgent public health issue. Gastric microecological dysbiosis (including bacteria, fungi, viruses, acid suppressants, antibiotics, and surgery) can lead to gastric immune dysfunction or result in a decrease in dominant bacteria and an increase in the number and virulence of pathogenic microorganisms, which in turn promotes development of GC. This review analyzes the relationship between gastric microecological dysbiosis and GC, elucidates dynamic alterations of the microbiota in Correa's cascade, and identifies certain specific microorganisms as potential biomarkers of GC to aid in early screening and diagnosis. In addition, this paper presents the potential of gastric microbiota transplantation as a therapeutic target for gastric cancer, providing a new direction for future research in this field.
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The COVID-19 is still spreading today, and it has caused great harm to human beings. The system at the entrance of public places such as shopping malls and stations should check whether pedestrians are wearing masks. However, pedestrians often pass the system inspection by wearing cotton masks, scarves, etc. Therefore, the detection system not only needs to check whether pedestrians are wearing masks, but also needs to detect the type of masks. Based on the lightweight network architecture MobilenetV3, this paper proposes a cascaded deep learning network based on transfer learning, and then designs a mask recognition system based on the cascaded deep learning network. By modifying the activation function of the MobilenetV3 output layer and the structure of the model, two MobilenetV3 networks suitable for cascading are obtained. By introducing transfer learning into the training process of two modified MobilenetV3 networks and a multi-task convolutional neural network, the ImagNet underlying parameters of the network models are obtained in advance, which reduces the computational load of the models. The cascaded deep learning network consists of a multi-task convolutional neural network cascaded with these two modified MobilenetV3 networks. A multi-task convolutional neural network is used to detect faces in images, and two modified MobilenetV3 networks are used as the backbone network to extract the features of masks. After comparing with the classification results of the modified MobilenetV3 neural network before cascading, the classification accuracy of the cascading learning network is improved by 7%, and the excellent performance of the cascading network can be seen.
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The recombination activating gene 1 (RAG1) is essential for V(D)J recombination during T- and B-cell development. In this study, we presented a case study of a 41-day-old female infant who exhibited symptoms of generalized erythroderma, lymphadenopathy, hepatosplenomegaly, and recurrent infections including suppurative meningitis and septicemia. The patient showed a T+B-NK+ immunophenotype. We observed an impaired thymic output, as indicated by reduced levels of naive T cells and sjTRECs, coupled with a restricted TCR repertoire. Additionally, T-cell CFSE proliferation was impaired, indicating a suboptimal T-cell response. Notably, our data further revealed that T cells were in an activated state. Genetic analysis revealed a previously reported compound heterozygous mutation (c. 1186C > T, p. R396C; c. 1210C > T, p. R404W) in the RAG1 gene. Structural analysis of RAG1 suggested that the R396C mutation might lead to the loss of hydrogen bonds with neighboring amino acids. These findings contribute to our understanding of RAG1 deficiency and may have implications for the development of novel therapies for patients with this condition.
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Proteínas de Homeodominio , Inmunodeficiencia Combinada Grave , Femenino , Humanos , Lactante , Genes RAG-1 , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Mutación , Inmunodeficiencia Combinada Grave/genética , Linfocitos TRESUMEN
The number of plastics is increasing owing to the rapid development of the plastics industry. Microplastics (MPs) are formed during the use of both petroleum-based plastics and newly developed bio-based plastics. These MPs are inevitably released into the environment and are enriched in wastewater treatment plant sludge. Anaerobic digestion is a popular sludge stabilization method for wastewater treatment plants. Understanding the potential impacts of different MPs on anaerobic digestion is critical. This paper provides a comprehensive review of the mechanisms of petroleum-based MPs and bio-based MPs in anaerobic digestion methane production and compares their potential effects on biochemical pathways, key enzyme activities, and microbial communities. Finally, it identifies problems that must be solved in the future, proposes the focus of future research, and predicts the future development direction of the plastics industry.
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Microplásticos , Plásticos , Aguas del Alcantarillado , Aguas Residuales , Eliminación de Residuos Líquidos/métodos , AnaerobiosisRESUMEN
Objectives: This study aimed to determine patients' perceived benefits of a WeChat applet for self-management of patients with neurogenic bladder (NGB) and identify the key factors hindering their adoption. Methods: In the qualitative study, 19 NGB patients were invited for semi-structured interviews. They were hospitalized in the rehabilitation departments of two tertiary hospitals in Shenzhen and tried out the self-management applet for two weeks. Data were analyzed using the content analysis method. Results: The results indicated that the WeChat applet of self-management was helpful and embraced by the NGB patients. Three perceived benefits were identified 1) being accessible, flexible, and intuitive to users, 2) driving bladder self-management, and 3) directing the way for care partners and family members. Challenges hindering the adoption of the applet included 1) negative attitudes of patients towards bladder self-management and patient characteristics, 2) concerns about the risks of mHealth, and 3) the necessity of applet upgrading. Conclusion: This study showed feasibility of the WeChat applet for self-management among NGB patients to meet their needs for access to information during hospitalization and after discharge. The study also identified facilitators and barriers to patient use, providing valuable information for healthcare providers to implement mHealth interventions to promote self-management among NGB patients.
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Understanding the underlying interaction between nanoparticle and organelles is conclusive to the nanotoxicology. According to existing literatures, lysosome is a crucial target of the nanoparticle carrier. Meanwhile, mitochondria could provide the essential energy for nanopaticles entering/exiting the cell. Based on the investigation of lysosome-mitochondria connection, we decoded the effects of low-dose ZIF-8 on energy metabolism, which are still largely obscure beforehand. In this research, low-dose ZIF-8 NPs were utilized to explore the effects on vascular endothelial cells, the first cells exposed to NPs during intravenous injection. Consequently, ZIF-8 could damage the energy metabolism, mainly manifested as mitochondrial fission, the decreased ATP production, and lysosomal dysfuction, which would subsequently affect the cell survival, proliferation and protein expression. This study highlights the fundamental understanding for exploring the regulation of nanoscale ZIF-8 in biological processes and its further application in biomedical field.
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Enfermedades Metabólicas , Nanopartículas , Zeolitas , Humanos , Zeolitas/toxicidad , Células Endoteliales/metabolismo , Nanopartículas/toxicidad , Mitocondrias/metabolismo , Lisosomas/metabolismo , Metabolismo EnergéticoRESUMEN
In order to explore the characteristics of organic carbon mineralization and the variation law of organic carbon components of an artificial forest in a loess hilly area, an artificial Robinia pseudoacacia forest restored for 13 years and the adjacent slope farmland were selected as the research objects, and indoor culture experiments under three different temperature treatments (15, 25, and 35â) were carried out. The results indicated that the mineralization rate of soil organic carbon decreased sharply at first and then stabilized. The cumulative release of organic carbon increased rapidly in the initial stage of culture and gradually slowed in the later stage. Soil organic carbon mineralization in sloping farmland was more sensitive to temperature change, and its temperature sensitivity coefficient Q10 was 1.52, whereas that in R. pseudoacacia forest land was only 1.38. According to the fitting of the single reservoir first-order dynamic equation, the soil mineralization potential Cp of R. pseudoacacia forest land and slope farmland was between 2.02-4.32 g·kg-1 and 1.25-3.17 g·kg-1, respectively, that is, the mineralization potential of the R. pseudoacacia forest was higher. During the cultivation period, the content of various active organic carbon components decreased with time, and that in the R. pseudoacacia forest land was greater than that in the slope land. The cumulative carbon release of soil was significantly positively correlated with the contents of MBC and DOC (P<0.05), and Q10 (15-25â) was negatively correlated with the contents of SOC, EOC, and SWC (P<0.05). These results could provide some reference for the study of soil carbon sequestration in loess hilly regions under climate change.
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Robinia , Suelo , Carbono/análisis , Nitrógeno/análisis , Bosques , Carbón Orgánico , ChinaRESUMEN
The translation behaviors of oscillating bubbles are closely related to the polymerizations and dispersions between them, which are crucial for the ultrasonic cavitation effect. In this study, six types of translational motion of bubbles with a wide range of sizes (2-100 µm) in the R01-R02 plane are investigated. Our results demonstrate that in addition (to the 2nd order harmonic), the 1/2 order subharmonic can change the bubble pairs from the three states of the attraction, stable after attraction, and repulsion to that of the repulsion, coalescence, and attraction, respectively. Furthermore, within the range of the main resonance radius and the 1/2 order subharmonic resonance radius, the chaotic bubble pairs with alternating attractive and repulsive forces appear in the region between the coalescence pairs and stable pairs after attraction. Finally, the corresponding physical mechanisms of the chaotic translational motions are also revealed.
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Ultrasonido , VibraciónRESUMEN
BACKGROUND: Inappropriate weight gain during pregnancy may present risks for maternal and newborn health. Pregnancy is considered the optimal time to intervene on women's health behaviors such as eating habits and physical activity. However, current clinical practice guidelines for weight management during pregnancy were not fully based on randomized trials, thus lacking specific "active intervention ingredients" that are proven effective in achieving appropriate gestational weight gain. Therefore it is essential to develop and implement an evidence-based weight management program for pregnant women. OBJECTIVE: To examine the effects of a midwife-led weight management program on improving appropriate gestational weight gain, health literacy, experience of antenatal care, and maternal and neonatal outcomes among Chinese pregnant women. DESIGN: A two-group randomized controlled trial. SETTINGS AND PARTICIPANTS: A total of 426 pregnant women were recruited from a tertiary women's hospital in eastern China. METHODS: Participants were randomly allocated to either intervention group (nâ¯=â¯213) or control group (nâ¯=â¯213). Women in the intervention group participated in a midwife-led weight management program during pregnancy, while women in the control group received the conventional obstetrician-led antenatal care. We assessed women at the first antenatal contact, 35-36â¯weeks gestation and 2-3â¯days postpartum. Data on gestational weight gain, health literacy, experience of antenatal care, and maternal and neonatal outcomes were compared between the two groups. Dummy variable analysis was conducted to reveal the effect of weight management program on gestational weight gain. RESULTS: The overall gestational weight gain between the two groups was not statistically different (tâ¯=â¯-1.377, Pâ¯=â¯0.170). Compared with women in the control group, the odds of having inappropriate gestational weight gain was lower in the intervention group (ORâ¯=â¯0.270, 95%CI 0.169, 0.431). Further subgroup analyses showed that women in the intervention group had lower risk of inadequate gestational weight gain (ORâ¯=â¯0.305, 95%CI 0.180, 0.515) and excessive gestational weight gain (ORâ¯=â¯0.236, 95%CI 0.138, 0.404) than those in the control group. The score of experience of antenatal care was significantly higher in the midwife-led weight management group than that in the control group (193.70⯱â¯18.51 versus 165.70⯱â¯28.23, Pâ¯<â¯0.001). Women's health literacy score was higher in the intervention group than control group [74.41 (69.57, 81.77) versus 71.88 (66.23, 77.18), Pâ¯=â¯0.004]. CONCLUSION: Compared with the conventional antenatal care, the midwife-led weight management program could facilitate appropriate gestational weight gain, enhance health literacy, and promote positive experience of antenatal care for Chinese pregnant women.
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Ganancia de Peso Gestacional , Partería , Programas de Reducción de Peso , Recién Nacido , Femenino , Embarazo , Humanos , Mujeres Embarazadas , Atención PrenatalRESUMEN
INTRODUCTION: Neurogenic lower urinary tract dysfunction (NLUTD) both threatens the health of affected patients long-term and also has a significantly negative impact on the patients' quality of life. present, many clinical practice guidelines (CPGs) have been developed for NLUTD patients, but these CPGs may confuse healthcare professionals and patients due to their great difference in terms of scope, quality and content. This review aims to identify the CPGs for NLUTD patients published from 2012 to 2022, assess their quality and then analyse them in an integrated manner. METHODS AND ANALYSIS: We will systematically search electronic healthcare databases (English databases including PubMed, EMBASE, OVID, Scopus, Web of Science, Cochrane Library, CINAHL, UpToDate, and Best Practice and Chinese databases including China National Knowledge Infrastructure, Wanfang Database, VIP Periodical Resource Integration Service Platform and SinoMed), online CPG repositories and relevant professional association websites to identify eligible CPGs. The CPGs published in English and Chinese with full texts available within the period from January 2012 to March 2022 will be included in this study. The Appraisal of Guidelines for Research and Evaluation (AGREE) II will be used to assess the quality of included CPGs. According to the predesigned data table, the general characteristics of these CPGs, proposed recommendations and their quality of evidence, strength of recommendation and other information will be extracted. Qualitative thematic analysis will be applied to the extracted recommendations. A summary of the proposed recommendations, their quality of evidence, strength of recommendation and other information will eventually be described in a table. This review is expected to identify knowledge gaps in current CPGs and to identify the areas of the proposed recommendations derived from low-level evidence. ETHICS AND DISSEMINATION : This systematic review does not involve the participation of any subjects, and therefore no ethical approval is required. The findings of this review will be published in a peer-reviewed journal and disseminated via conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022318180.
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Calidad de Vida , Sistema Urinario , Humanos , China , Bases de Datos Factuales , Revisiones Sistemáticas como AsuntoRESUMEN
Chemotherapy and immunotherapy for pancreatic ductal adenocarcinoma (PDAC) have limited success for the intricated surrounding cancer microenvironment. Hypoxic microenvironment in PDAC causes the activation of multiple different molecules and signaling pathways compared with normoxia. We studied the roles of BNIP3 for the migration and proliferation of PDAC and Panc1 cells in vitro. In the present study, we found that BNIP3 expression was elevated and enhanced the migration and proliferation of CFPAC-1 and Panc1 cells under hypoxia. The upregulation of BNIP3 was important for the autophagic activation, while inhibition of autophagy with siRNA targeting Atg5 and Atg7 impaired the hypoxia-induced cell migration and proliferation. Additionally, blocking ERK1/2 mitogen-activated protein kinase (MAPK) signaling with PD98058 significantly down-regulated BNIP3 expression, autophagic activation, as well as the migration and proliferation of CFPAC-1 and Panc1 cells under hypoxia. Collectively, our results here uncover a hitherto unknown hypoxia-BNIP3-autophagy axis in modulating the migration and proliferation and provide a potential intriguing drug target for the therapy of PDAC.
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The 3D CAD software has obvious advantages in appearance imitating and geometric structure modeling for fabrics. In contemporary 3D CAD fabric systems, only uniform yarns are involved in studies on fabric geometric structures, due to technological limitations, whereas objectives such as irregular/uneven 3D yarns have not been considered much. As the fabric structure or the central curve of the yarn changes, it is difficult to reflect the changed positions of the effect spots of the pre-designed uneven 3D yarns accordingly. In this paper, a key-point-mapping algorithm between the source yarn and the target curve is proposed to reflect the position change in effect spots when the fabric structure changes. By using the shape-preserving quasi-uniform cubic B-spline curve, a simple 3D irregular source yarn is designed using key points and setting their corresponding base cross-sections. The mapping is based on the principle that the lengths of the curve between the key points and the contours of the corresponding base cross-sections of the source yarn remain unchanged. Finally, the control grid of the new 3D yarn in the fabric structure is automatically generated. According to the examples and error analysis, the mapping technique can be applied to arbitrary given fabric structures, and the effect spots of the irregular 3D yarn are reasonably distributed as expected.
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T cell immune dysfunction is a prominent characteristic of chronic lymphocytic leukemia (CLL) and the main cause of failure for immunotherapy and multi-drug resistance. There remains a lack of specific biomarkers for evaluating T cell immune status with outcome for CLL patients. T cell factor 1 (TCF1, encoded by the TCF7 gene) can be used as a critical determinant of successful anti-tumor immunotherapy and a prognostic indicator in some solid tumors; however, the effects of TCF1 in CLL remain unclear. Here, we first analyzed the biological processes and functions of TCF1 and co-expressing genes using the GEO and STRING databases with the online tools Venny, Circos, and Database for Annotation, Visualization, and Integrated Discovery (DAVID). Then the expression and prognostic values of TCF1 and its partner gene B cell leukemia/lymphoma 11B (BCL11B) were explored for 505 CLL patients from 6 datasets and validated with 50 CLL patients from Henan cancer hospital (HNCH). TCF1 was downregulated in CLL patients, particularly in CD8+ T cells, which was significantly correlated with poor time-to-first treatment (TTFT) and overall survival (OS) as well as short restricted mean survival time (RMST). Function and pathway enrichment analysis revealed that TCF1 was positively correlated with BCL11B, which is involved in regulating the activation and differentiation of T cells in CLL patients. Intriguingly, BCL11B was highly consistent with TCF1 in its decreased expression and prediction of poor prognosis. More importantly, the combination of TCF1 and BCL11B could more accurately assess prognosis than either alone. Additionally, decreased TCF1 and BCL11B expression serves as an independent risk factor for rapid disease progression, coinciding with high-risk indicators, including unmutated IGHV, TP53 alteration, and advanced disease. Altogether, this study demonstrates that decreased TCF1 and BCL11B expression is significantly correlated with poor prognosis, which may be due to decreased TCF1+CD8+ T cells, impairing the effector CD8+ T cell differentiation regulated by TCF1/BCL11B.
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Factor Nuclear 1-alfa del Hepatocito , Leucemia Linfocítica Crónica de Células B , Proteínas Represoras , Proteínas Supresoras de Tumor , Biomarcadores/metabolismo , Factor Nuclear 1-alfa del Hepatocito/genética , Factor Nuclear 1-alfa del Hepatocito/metabolismo , Humanos , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/metabolismo , Leucemia Linfocítica Crónica de Células B/patología , Pronóstico , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Factor 1 de Transcripción de Linfocitos T/genética , Factor 1 de Transcripción de Linfocitos T/metabolismo , Factores de Transcripción , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismoRESUMEN
Acute myeloid leukemia (AML) is prone to relapse. Targeted therapy with a specific inhibitor of the anti-apoptotic protein Bcl-2 ABT-199 is an effective method for relapsed and refractory patients, but drug resistance is likely, which is primarily related to high Mcl-1 and S100A8 expression. All-trans retinoic acid (ATRA) can inhibit Bcl-2 and Mcl-1 expression. The study purpose was to determine whether ATRA can enhance the antileukemia effect of ABT-199 on AML cells. Our data showed that ATRA combined with ABT-199 exerts a synergistic antileukemic effect by inducing apoptosis and cell cycle arrest in AML. In vivo, combination therapy prolonged the survival of AML xenograft mice. The possible mechanism involves promoting apoptosis through downregulation of S100A8 expression by inhibiting the PI3K/AKT signaling pathway. This study provides a potential treatment strategy and theoretical support for overcoming the clinical ABT-199 resistance problem in AML patients.