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Background: Currently, studies found that the humanistic care ability of nurses is at low level in China, resulting in patients' concerns and dissatisfaction regarding the lack of empathy among nurses. We aimed to explore the factors that influence nurses' humanistic care ability, providing a new perspective on improving patient satisfaction and promote high quality medical services. Methods: A multi-center cross-sectional study recruited nurses from tertiary and secondary hospitals in China between July 2022 and August 2022. Data concerning self-developed questions on nurses' socio-demographic data and Caring Ability Inventory (CAI) were collected through the Questionnaire Star Platform, using a multi-stage sampling method. Results: The total score for the level of caring ability among the 15,653 surveyed Chinese nurses was 192.16 ± 24.94. Various factors significantly influence the level of humanistic care ability, including professional title, department, degree of passion for the job, job satisfaction, emphasis on self-care, participation in humanistic care training, support from family for the job, relationships with colleagues, satisfaction with salary, and previous experience working in pilot wards emphasizing humanistic care (p < 0.01). Conclusion: At present, nurses exhibit a comparatively modest proficiency in humanistic care ability. Numerous factors contribute to this situation. Nursing administrators ought to enhance the scope of humanistic care practices, conduct consistent professional training sessions, advocate for the implementation of model wards emphasizing humanistic care, foster a supportive organizational culture conducive to nurses, and underscore the significance of both nurturing nurses and promoting self-care among them.
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Purpose: Humanistic caring in clinical practice is important for quality care and patient satisfaction. This study aimed to assess patient satisfaction with humanistic care for emergency patients in China and its associated factors. Methods: From October 2023 to December 2023, a multi-center cross-sectional survey was conducted across 28 provinces and 87 hospitals in China, using a sampling method for inpatients in emergency department. Patient satisfaction with humanistic care was evaluated by a self-developed questionnaire with 32 items across 6 dimensions. Stepwise multiple linear regression was used to explore associated factors. Results: A total of 3,003 valid questionnaires were successfully collected, with an effective rate of 86.05%. The emergency patients' total mean humanistic caring satisfaction score was 4.67 ± 0.66. Age, medical insurance type, specialized emergency department visited, waiting times, whether had accompanied person, hospital level, and hospital type are correlated factors (P < 0.05) regarding humanistic caring satisfaction. The correlation analysis showed perceived value, and its three dimensions were moderately correlated with humanistic caring satisfaction. The multiple linear regression showed waiting time (ß = -0.219, P < 0.05), whether had accompanied person (ß = -0.192, P < 0.05), hospital level (ß = -0.137, P < 0.05), functional value (ß = 0.197, P < 0.05), and emotional value (ß = 0.418, P < 0.05) were strong predictors. Conclusion: Hospitals at all levels should improve patients' perceived value, shorten waiting times, and provide caregivers with improved humanistic care in the emergency department.
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Serviço Hospitalar de Emergência , Humanismo , Satisfação do Paciente , Humanos , Estudos Transversais , China , Feminino , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente/estatística & dados numéricos , Adulto , Inquéritos e Questionários , Serviço Hospitalar de Emergência/estatística & dados numéricos , Idoso , Hospitais , Adolescente , Adulto JovemRESUMO
Tetrandrine (TET) is a natural bis-benzylisoquinoline alkaloid isolated from Stephania species with a wide range of biological and pharmacologic activities; it mainly serves as an anti-inflammatory agent or antitumor adjuvant in clinical applications. However, limitations such as prominent hydrophobicity, severe off-target toxicity, and low absorption result in suboptimal therapeutic outcomes preventing its widespread adoption. Nanoparticles have proven to be efficient devices for targeted drug delivery since drug-carrying nanoparticles can be passively transported to the tumor site by the enhanced permeability and retention (EPR) effects, thus securing a niche in cancer therapies. Great progress has been made in nanocarrier construction for TET delivery due to their outstanding advantages such as increased water-solubility, improved biodistribution and blood circulation, reduced off-target irritation, and combinational therapy. Herein, we systematically reviewed the latest advancements in TET-loaded nanoparticles and their respective features with the expectation of providing perspective and guidelines for future research and potential applications of TET.
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Shandong province, located in the Lower Yellow River, is one of the birthplaces of ancient Chinese civilization. However, the comprehensive genetic histories of this region have remained largely unknown until now due to a lack of ancient human genomes. Here, we present 21 ancient genomes from Shandong dating from the Warring States period to the Jin-Yuan Dynasties. Unlike the early Neolithic samples from Shandong, the historical samples are most closely related to post-Late Neolithic populations of the Middle Yellow River Basin, suggesting a population turnover in Shandong from the Neolithic Age to the Historical era. In addition, we detect a close genetic affinity between the historical samples in Shandong and present-day Han Chinese, showing long-term genetic stability in Han Chinese at least since the Warring States period.
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Targeted delivery and precise release of toxins is a prospective strategy for the treatment of triple-negative breast cancer (TNBC), yet the flexibility to incorporate both properties simultaneously remains tremendously challenging in the X-drug conjugate fields. As critical components in conjugates, linkers could flourish in achieving optimal functionalities. Here, we pioneered a pH-hypersensitive tumor-targeting aptamer AS1411-triptolide conjugate (AS-TP) to achieve smart release of the toxin and targeted therapy against TNBC. The multifunctional acetal ester linker in the AS-TP site-specifically blocked triptolide toxicity, quantitatively sustained aptamer targeting, and ensured the circulating stability. Furthermore, the aptamer modification endowed triptolide with favorable water solubility and bioavailability and facilitated endocytosis of conjugated triptolide by TNBC cells in a nucleolin-dependent manner. The integrated superiorities of AS-TP promoted the preferential intra-tumor triptolide accumulation in xenografted TNBC mice and triggered the in-situ triptolide release in the weakly acidic tumor microenvironment, manifesting striking anti-TNBC efficacy and virtually eliminated toxic effects beyond clinical drugs. This study illustrated the therapeutic potential of AS-TP against TNBC and proposed a promising concept for the development of nucleic acid-based targeted anticancer drugs.
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Aptâmeros de Nucleotídeos , Diterpenos , Compostos de Epóxi , Fenantrenos , Neoplasias de Mama Triplo Negativas , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Diterpenos/química , Compostos de Epóxi/farmacologia , Compostos de Epóxi/uso terapêutico , Compostos de Epóxi/química , Fenantrenos/farmacologia , Fenantrenos/uso terapêutico , Fenantrenos/química , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Animais , Humanos , Camundongos , Feminino , Aptâmeros de Nucleotídeos/farmacologia , Aptâmeros de Nucleotídeos/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto , Linhagem Celular Tumoral , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêuticoRESUMO
Objectives: This study aimed to identify the key elements and develop a formation mechanism model of quality geriatric care behavior for nursing assistants. Methods: This qualitative research employed the strategy of grounded theory proposed by Strauss and Corbin. Furthermore, the data was collected by participatory observation and semi-structured interviews. A total of 12 nursing managers, 63 nursing assistants, and 36 older people from 9 nursing homes in 6 cities were interviewed, whereas for the observatory survey, participants were recruited from 2 nursing homes. Results: The comparative and analysis process revealed 5 key elements of quality geriatric care behavior, including holistic care, personalized care, respect, positive interaction, and empowerment. Based on the Capability-Opportunity-Motivation-Behavior (COM-B) model, key elements and the 3 stages of quality geriatric care behavior (negative behavior cognition stage, practice exchange run-in stage, and positive behavior reinforcement stage), the theoretical framework of the formation mechanism was established. Conclusion: The results indicated that nursing assistants' capabilities, motivation, and organizational and environmental support are vital for quality care behaviors. The theoretical framework established in this study provides theoretical support and practical reference to policymakers, institutional administrators, and healthcare professionals for improving nursing assistant's care behaviors.
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Teoria Fundamentada , Assistentes de Enfermagem , Casas de Saúde , Pesquisa Qualitativa , Qualidade da Assistência à Saúde , Humanos , Casas de Saúde/normas , Feminino , Masculino , Idoso , Adulto , Pessoa de Meia-Idade , Entrevistas como AssuntoRESUMO
Background: Explore the efficacy and safety of donor-derived CLL-1 chimeric antigen receptor T-cell therapy (CAR-T) for relapsed/refractory acute myeloid leukemia (R/R AML) bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT) after remission. Case presentation: An adult R/R AML patient received an infusion of donor-derived CLL-1 CAR-T cells, and the conditioning regimen bridging to allo-HSCT was started immediately after remission on day 11 after CAR-T therapy upon transplantation. Then, routine post-HSCT monitoring of blood counts, bone marrow (BM) morphology, flow cytometry, graft-versus-host disease (GVHD) manifestations, and chimerism status were performed. Result: After CAR-T therapy, cytokine release syndrome was grade 1. On day 11 after CAR-T therapy, the BM morphology reached complete remission (CR), and the conditioning regimen bridging to allo-HSCT started. Leukocyte engraftment, complete donor chimerism, and platelet engraftment were observed on days +18, +23, and +26 post-allo-HSCT, respectively. The BM morphology showed CR and flow cytometry turned negative on day +23. The patient is currently at 4 months post-allo-HSCT with BM morphology CR, negative flow cytometry, complete donor chimerism, and no extramedullary relapse/GVHD. Conclusion: Donor-derived CLL-1 CAR-T is an effective and safe therapy for R/R AML, and immediate bridging to allo-HSCT after remission may better improve the long-term prognosis of R/R AML.
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Transplante de Células-Tronco Hematopoéticas , Imunoterapia Adotiva , Leucemia Mieloide Aguda , Transplante Homólogo , Humanos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/imunologia , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/efeitos adversos , Masculino , Receptores de Antígenos Quiméricos/imunologia , Indução de Remissão , Doença Enxerto-Hospedeiro/etiologia , Pessoa de Meia-Idade , Condicionamento Pré-Transplante/métodos , Adulto , Resultado do Tratamento , Doadores de Tecidos , FemininoRESUMO
Background: Metagenomic next-generation sequencing (mNGS) is a novel non-invasive and comprehensive technique for etiological diagnosis of infectious diseases. However, its practical significance has been seldom reported in the context of hematological patients with high-risk febrile neutropenia, a unique patient group characterized by neutropenia and compromised immune responses. Methods: This retrospective study evaluated the results of plasma cfDNA sequencing in 164 hematological patients with high-risk febrile neutropenia. We assessed the diagnostic efficacy and clinical impact of mNGS, comparing it with conventional microbiological tests. Results: mNGS identified 68 different pathogens in 111 patients, whereas conventional methods detected only 17 pathogen types in 36 patients. mNGS exhibited a significantly higher positive detection rate than conventional methods (67.7% vs. 22.0%, P < 0.001). This improvement was consistent across bacterial (30.5% vs. 9.1%), fungal (19.5% vs. 4.3%), and viral (37.2% vs. 9.1%) infections (P < 0.001 for all comparisons). The anti-infective treatment strategies were adjusted for 51.2% (84/164) of the patients based on the mNGS results. Conclusions: mNGS of plasma cfDNA offers substantial promise for the early detection of pathogens and the timely optimization of anti-infective therapies in hematological patients with high-risk febrile neutropenia.
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Neutropenia Febril , Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Humanos , Metagenômica/métodos , Masculino , Estudos Retrospectivos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Feminino , Pessoa de Meia-Idade , Neutropenia Febril/microbiologia , Neutropenia Febril/sangue , Neutropenia Febril/diagnóstico , Adulto , Idoso , Adulto Jovem , Adolescente , Idoso de 80 Anos ou mais , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/microbiologia , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/classificação , Micoses/diagnóstico , Micoses/microbiologia , Viroses/diagnóstico , Viroses/virologiaRESUMO
KN046, a bispecific antibody targeting PD-L1 and CTLA-4, presents a promising therapeutic option for metastatic non-small cell lung cancer (NSCLC). In this multicenter phase 2 trial, patients with nonsquamous (non-sq) NSCLC receive pemetrexed, whereas those with sq-NSCLC receive paclitaxel, plus KN046 and carboplatin. Following four cycles, maintenance therapy includes KN046 with pemetrexed for non-sq-NSCLC and KN046 for sq-NSCLC. The objective response rate is 46.0%, and the median duration of response is 8.1 months. The median progression-free and overall survival are 5.8 and 26.6 months, respectively. The common adverse events include anemia (87.4%), loss of appetite (72.4%), and neutropenia (70.1%). The most prevalent immune-related adverse event is pruritus (28.7%). These findings indicate that first-line treatment with KN046 and chemotherapy is effective and tolerable in metastatic NSCLC patients, warranting further investigation in a larger phase 3 trial. The trial is registered at ClinicalTrials.gov (NCT04054531).
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Pemetrexede/uso terapêutico , Neoplasias Pulmonares/patologia , Antígeno B7-H1 , Antígeno CTLA-4 , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêuticoRESUMO
INTRODUCTION: Phosphatidylinositol 3-kinases (PI3Ks) overexpression can elicit cellular homeostatic dysregulation, which further contributes to tumorigenesis, with PI3Kα emerging as the most prevalent mutant isoform kinase among PI3Ks. Therefore, selective inhibitors targeting PI3Kα have attracted considerable interest in recent years. Molecular hybridization, with the advantage of simplified pharmacokinetics and drug-drug interactions, emerged as one of the important avenues for discovering potential drugs. OBJECTIVES: This study aimed to construct PI3Kα inhibitors by hybridization and investigate their antitumor activity and mechanism. METHODS: 26 quinazoline-2-indolinone derivatives were obtained by molecular hybridization, and their structure-activity relationship was analyzed by MTT, in vitro kinase activity and molecular docking. The biological evaluation of compound 8 was performed by transwell, flow cytometry, laser scanning confocal microscopy, Western blot, CTESA and immunohistochemistry. RESULTS: Here, we employed molecular hybridization methods to construct a series of quinazoline-2-indolinone derivatives as PI3Kα selective inhibitors. Encouragingly, representative compound 8 exhibited a PI3Kα enzymatic IC50 value of 9.11 nM and 10.41/16.99/37.53-fold relative to the biochemical selectivity for PI3Kß/γ/δ, respectively. Moreover, compound 8 effectively suppressed the viability of B16, HCT116, MCF-7, H22, PC-3, and A549 cells (IC50 values: 0.2 µM â¼ 0.98 µM), and dramatically inhibited the proliferation and migration of NSCLC cells, as well as induced mitochondrial apoptosis through the PI3K/Akt/mTOR pathway. Importantly, compound 8 demonstrated potent in vivo anti-tumor activity in non-small cell lung cancer mouse models without visible toxicity. CONCLUSIONS: This study presented a new avenue for the development of PI3Kα inhibitors and provided a solid foundation for novel QHIDs as potential future therapies for the treatment of NSCLC.
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AIMS: To explore the association between nurse managers' paternalistic leadership and nurses' perceived workplace bullying (WPB), as well as to examine the mediating role of organizational climate in this association. BACKGROUND: There is a lack of empirical evidence regarding the relationship between nurse managers' paternalistic leadership, organizational climate and nurses' perceived WPB. Clarifying this relationship is crucial to understand how paternalistic leadership influences WPB and for nursing managers to seek organizational-level solutions to prevent it. METHODS: A cross-sectional survey was performed from 4 January to 10 February 2022, in six tertiary hospitals in mainland China. Demographic information, Paternalistic Leadership Scale, Organizational Climate Scale and Negative Acts Questionnaire-Revised were used in the survey. Descriptive statistics, Spearman correlation analyses and a structural equation model were used for data analysis. RESULTS: A total of 5093 valid questionnaires were collected. Moral leadership and authoritarian leadership have both direct and indirect effects on WPB through the mediating effect of organizational climate. The former is negatively related to WPB and the latter is positively related to WPB. Benevolent leadership was only negatively associated with WPB via the mediating effect of organizational climate. CONCLUSION: The three components of paternalistic leadership have different effects on WPB through the mediating effect of organizational climate. Nurse managers are recommended to strengthen moral leadership, balance benevolent leadership, reduce authoritarian leadership and strive to create a positive organizational climate in their efforts to mitigate WPB among nurses. IMPACT: This study enhanced our comprehension of the relationship between different leadership styles and WPB. Greater emphasis should be placed on moral leadership in the promotion of nursing managers and nursing leadership training programs. Additionally, nursing managers should focus on establishing a positive organizational climate that helps to reduce WPB. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. This study did not involve patients, service users, caregivers or members of the public.
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Bullying , Liderança , Enfermeiros Administradores , Recursos Humanos de Enfermagem Hospitalar , Cultura Organizacional , Local de Trabalho , Humanos , Bullying/psicologia , Bullying/estatística & dados numéricos , Estudos Transversais , Enfermeiros Administradores/psicologia , Masculino , Feminino , Adulto , China , Recursos Humanos de Enfermagem Hospitalar/psicologia , Pessoa de Meia-Idade , Inquéritos e Questionários , Local de Trabalho/psicologia , Paternalismo , Atitude do Pessoal de SaúdeRESUMO
BACKGROUND: With the growing challenge of an aging population, addressing the needs of elderly individuals who face living difficulties and lack family support becomes increasingly difficult. Volunteer services are crucial in this context, yet their effectiveness is hindered by unclear service scopes and uncertain volunteer inclinations. AIM: To explore the role and specific preference of volunteers with nursing backgrounds in support of older adults living in the urban community. DESIGN, SETTING AND PARTICIPANTS: A descriptive qualitative study was conducted between September and October 2022. Twenty-three participants (hospital nurses [10], community nurses [4], nursing teachers [4] and nursing students [5]) were selected. Data analysis followed conventional content analysis. RESULTS: Nine major themes were identified based on interview data. Four themes described the service scope of nursing volunteers: (1) environment domain, (2) physiological domain, (3) psychosocial domain and (4) health-related behaviours domain. Another five themes highlighted the service inclination of these volunteers: (1) service frequency, (2) service duration per person/time, (3) service coverage, (4) service place and (5) service object. CONCLUSION: This study clarifies the service focus and scope of necessary support for volunteers, exploring the potential service capabilities of scarce volunteers to the greatest extent. Meanwhile, the results of this study also provide a foundation for stakeholders to fully exploit the synergy. The important findings of this study will help the government and relevant authorities better understand the service attributes of nursing volunteers, allowing them to develop detailed training plans and provide nursing volunteers with targeted support and assistance to meet the health expectations of urban community-living older adults in need. PATIENT OR PUBLIC CONTRIBUTION: Developing research questions, participation and conduct and provision and interpretation of evidence.
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Voluntários , Idoso , Humanos , Pesquisa Qualitativa , Vida IndependenteRESUMO
Porous organic cages (POCs) represent a notable category of porous materials, showing remarkable material properties due to their inherent porosity. Unlike extended frameworks which are constructed by strong covalent or coordination bonds, POCs are composed of discrete molecular units held together by weak intermolecular forces. Their structure and chemical traits can be systematically tailored, making them suitable for a range of applications including gas storage and separation, molecular separation and recognition, catalysis, and proton and ion conduction. This review provides a comprehensive overview of POCs, covering their synthesis methods, structure and properties, computational approaches, and applications, serving as a primer for those who are new to the domain. A special emphasis is placed on the growing role of computational methods, highlighting how advanced data-driven techniques and automation are increasingly aiding the rapid exploration and understanding of POCs. We conclude by addressing the prevailing challenges and future prospects in the field.
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Tetrandrine (TET) possesses multiple pharmacological activities and could suppress tumor proliferation via PI3K pathway inhibition. However, inferior antitumor activity and potential toxicity limit its clinical application. In the present study, a series of 14-sulfonamide and sulfonate TET derivatives were designed, synthesized, and evaluated for biological activities. Through structural-activity relationship studies, compound 3c with α, ß-unsaturated carbonyl group exhibited the most potent activity against all tested tumor cell lines (including Hela, HCT116, HepG2, MCF-7, and SHSY5Y), as well as negligible toxicity against normal cell lines LO2 and HEK293. Additionally, compound 3c effectively inhibited HCT116 and CT26 cell proliferation in vitro with increased cell proportion in the G2/M phase, activated the mitochondrial apoptosis pathway, and induced colon cancer cell apoptosis by suppressing the PI3K/AKT/mTOR pathway. The further molecular docking results confirmed that compound 3c is potentially bound to multiple residues in PI3K with a stronger binding affinity than TET. Ultimately, compound 3c dramatically suppressed tumor growth in the CT26 xenograft tumor model, without noticeable visceral toxicity detected in the high-dose group. In summary, compound 3c might present new insights for designing new PI3K inhibitors and be a potential candidate for colon cancer treatment.
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Benzilisoquinolinas , Neoplasias do Colo , Proteínas Proto-Oncogênicas c-akt , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fosfatidilinositol 3-Quinases/metabolismo , Simulação de Acoplamento Molecular , Células HEK293 , Serina-Treonina Quinases TOR/metabolismo , Linhagem Celular Tumoral , Apoptose , Proliferação de Células , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismoRESUMO
Objectives: To explore and analyze the influencing factors of depression in older adults living at home, so as to propose suggestions for improving the quality of older adults living at home. Methods: We conducted a cross-sectional study on 498 older adults living at home based on questionnaire survey on the general information, daily living ability, health status, and care perception (including self-care, care for cohabitants, and care for non-cohabitants) of older adults living at home, as well as their willingness to help each other, and analyzed the influencing factors of depression among older adults living at home. Results: The results showed a willingness to help older adults, self-care, and total activities of daily living (ADL), health status was an influential factor for depression in older adults (p < 0.05). Conclusion: It aims to take targeted measures, such as encouraging older adults at home to actively participate in mutual assistance activities for older adults and care for themselves, so as to prevent and reduce the occurrence of depression in older adults.
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Atividades Cotidianas , Serviços de Assistência Domiciliar , Humanos , Idoso , Depressão/epidemiologia , Estudos Transversais , Autocuidado/métodosRESUMO
BACKGROUND: With China's rapidly aging population, meeting the diverse care needs of senior citizens is becoming more challenging. Although voluntary social services have numerous advantages and are popular among older adults, there is little information on the need for assistance from volunteer-based social services, particularly those with a medical background, and influencing factors among urban home-based older adults. This study aimed to assess the need for assistance from voluntary services and related factors among urban home-based older adults in China. METHODS: A cross-sectional study was conducted in 2022 on communities in four cities in China. The 27-item Home-Based Older Adults Assistance Need Scale was used to measure the assistance needs of 498 participants aged 60 and above. Multiple linear regression models were conducted to identify salient variables associated with the need for assistance from voluntary services. RESULTS: The mean score of the need for assistance from voluntary services was 88.60 ± 24.37. The mean scores of the items examining four dimensions, namely, health maintenance, visiting communication, social intercourse, and daily life, were 3.64 ± 1.08, 3.49 ± 1.04, 3.33 ± 1.08, and 2.78 ± 1.08, respectively. The level of depression, willingness to assist older adults, attaching importance to health preservation, ability to self-comfort, desire to accept assistance from others, and the presence of more children or none at all were all positively correlated with the perceived need for assistance from voluntary services. In contrast, social care obtained from visiting medical institutions was negatively correlated. These seven factors explained 28.5% of the total variance. CONCLUSIONS: Urban home-based older adults in China were found to have significant requirements for assistance from volunteer services, and several complex factors were associated with more significant assistance needs. These findings may encourage the extremely limited numbers of social volunteers, particularly those with a medical background, to identify priorities in providing assistance services to the large numbers of urban home-based older adults and thus improve service delivery.
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Envelhecimento , População do Leste Asiático , Idoso , Humanos , China/epidemiologia , Estudos Transversais , Apoio SocialRESUMO
Acute myeloid leukemia (AML) is a large class of heterogeneous hematological malignancies with the highest incidence rate in acute leukemia. Its pathogenesis is still unclear, which may be related to genetics. According to the latest AML NCCN guidelines, genes involved in AML family genetic changes include RUNX1, ANKRD26, CEBPA. Finding new genes related to AML genetics is of great significance for predicting the prognosis of patients, developing targeted drugs, and selecting transplant donors. Here, we report a case of adult female AML patient whose three relatives suffered from hematological malignancies, including Waldenstrom macroglobulinemia, NK/T-cell lymphoma, and angioimmunoblastic T-cell lymphoma. The screen for genetic susceptibility genes related to blood and immune system diseases was carried out, and the result showed that the patient herself, her son, her daughter, and her two cousins all had STK11 p.F354L and/or THBD p.D486Y mutations. At present, there is no research or case report on the relationship between STK11/THBD and family aggregation of hematological malignancies. We report for the first time that an AML patient with STK11 and THBD mutations has a family aggregation of hematological malignancies, and consider that STK11 and THBD may be related to family genetic changes which ultimately cause the family aggregation of hematological malignancies.
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Triple-negative breast cancer (TNBC), as the most aggressive subtype of breast cancer, presents a scarcity of miraculous drugs in suppressing its proliferation and metastasis. Bruceine A (BA) is a functional group-rich quassin compound with extensive and distinctive pharmacological activities. Within the present study, we investigated the capabilities of BA in suppressing TNBC proliferation and metastasis as well as its potential mechanisms. The results displayed that BA dramatically repressed the proliferation of MDA-MB-231 and 4T1 cells with corresponding IC50 values of 78.4 nM and 524.6 nM, respectively. Concurrently, BA arrested cells in G1 phase by downregulating cycle-related proteins Cyclin D1 and CDK4. Furthermore, BA distinctly induced mitochondrial dysfunction as manifested by diminished mitochondrial membrane potential, elevated reactive oxygen species generation, minimized ATP production, and Caspase-dependent activation of the mitochondrial apoptosis pathway. Additionally, BA restrained the invasion and metastasis of TNBC cells by repressing MMP9 and MMP2 expression. Intriguingly, after pretreatment with MEK activator C16-PAF, the inhibitory effect of BA on MEK/ERK pathway was notably diminished, while the proliferation suppression and metastasis repression exerted by BA were all strikingly curtailed. Molecular docking illustrated that BA potently combined with residues on the MEK1 protein with the presence of diverse intermolecular interactions. Ultimately, BA effectively suppressed tumor growth in the 4T1 xenograft tumor model with no detectable visceral toxicity in the high-dose group and, astonishingly, repressed tumor metastasis in the 4T1-luc lung metastasis model. Collectively, our study demonstrates that BA is a promising chemotherapeutic agent for treating TNBC and suppressing lung metastasis.
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Neoplasias Pulmonares , Quassinas , Neoplasias de Mama Triplo Negativas , Humanos , Sistema de Sinalização das MAP Quinases , Proliferação de Células , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , Simulação de Acoplamento Molecular , Apoptose , Quassinas/farmacologia , Mitocôndrias , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND: Humanistic care management is a necessary measure to improve the motivation and initiative of clinical nurses and is the foundation to improve the quality of nursing. Understanding the current status and identifying the influencing factors that promote or hinder humanistic care behaviors is essential. This study investigated the current status and experiences of nurse managers' caring behaviors toward clinical nurses. METHODS: We conducted a mixed-methods study with an explanatory sequential design. A survey on the nurse managers' caring behaviors in 101 hospitals from 23 provinces and four municipalities in China was investigated (n = 2022). Then, semi-structured interviews were conducted to obtain information about the participants' experiences associated with the performance of caring behaviors (n = 27). RESULTS: Survey data demonstrated that the nurse managers' overall caring behaviors were moderately good. The total scoring rate was 88.55%, and the overall score was 161.19 ± 20.68. Qualitative data revealed that the capacity of nurse managers and clinical nurses, opportunity, and motivation to implement humanistic care are key influencing factors of caring behaviors. CONCLUSIONS: The results suggested that intrinsic motivation, organizational support, and the humanistic care capabilities of clinical nurses and nurse managers are vital to implementing care behaviors. Thus, successful humanistic care management requires a concerted effort at the individual and organizational levels.