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1.
Front Med (Lausanne) ; 11: 1391907, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39086941

RESUMEN

Background: Studies have shown that work readiness is closely related to nurses' role adaptation, career development, and patient safety. However, we know little about the nursing students' work readiness and its influencing factors before participating in a nurse residency program, and whether factors have changed from before. Aim: (1) To investigate the work readiness of nursing students ready to engage in a nurse residency program; (2) to identify the factors affecting the nursing students' work readiness and the associations between emotional intelligence and work readiness; and (3) to discuss the changes of factors affecting nursing students' work readiness. Design: An online, multicenter cross-sectional study. Methods: 878 nursing students from eight tertiary hospitals in Chongqing, China were recruited. The online investigation used the General Information Questionnaire, the Nursing Students' Work Readiness Scale, and the Emotional Intelligence scale. The data were analyzed using IBM SPSS V23.0. Results: 768 valid questionnaires were included in this study. The nurses obtained a work readiness score of 277.08 ± 44.39 and an emotional intelligence score of 89.57 ± 13.89. Univariate analysis revealed that the following factors affected work readiness: age, sex, family support for becoming a nurse, voluntary choice of nursing major, previous experience as a student cadre, scholarship recipient status, willingness to engage in nursing work during the COVID-19 pandemic and confidence in clinical nursing practice. Frequent incidents of violence, poor salary for nurses for the nurse residency program, and low social acceptance were the top three reasons for decreased confidence in clinical nursing among nursing students. Furthermore, multiple linear regression analysis indicated that age, voluntary choice of nursing major, student leadership experience, confidence in clinical nursing work, self-emotion, and emotional application significantly influenced nurses' work readiness. Conclusion: Clinical instructors and administrators should dynamically assess nurses' work readiness, prioritize individuals aged ≤23, who have chosen the nursing profession involuntarily, lack prior experience as student cadres, and exhibit low confidence in clinical nursing work. This focus will enhance their emotional self-management skills and ability to apply emotions effectively, improving their work readiness and training efficacy.

2.
BMC Cancer ; 24(1): 950, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095737

RESUMEN

OBJECTIVE: To investigate the impact of response to induction chemotherapy (IC) on survival outcomes in patients with locally advanced nasopharyngeal carcinoma (LANPC) and evaluate the efficacy of adding nimotuzumab to concurrent chemoradiotherapy (CCRT) based on different responses to IC. METHODS: We retrospectively included patients with stage III-IVA NPC who underwent IC with and without nimotuzumab during CCRT. Statistical analysis included the chi-square test, propensity score matching, Kaplan-Meier survival analysis, and Cox proportional hazards model. RESULTS: Among 383 identified patients, 216 (56.4%) received nimotuzumab during CCRT, while 167 (43.6%) did not. Following IC, 269 (70.2%) patients showed a complete response (CR) or partial response (PR), and 114 (29.8%) had stable disease (SD) or progressive disease (PD). The response to IC independently influenced disease-free survival (DFS) and overall survival (OS). Patients achieving CR/PR demonstrated significantly higher 3-year DFS (80.3% vs. 70.6%, P = 0.031) and OS (90.9% vs. 83.2%, P = 0.038) than those with SD/PD. The addition of nimotuzumab during CCRT significantly improved DFS (P = 0.006) and OS (P = 0.037) for CR/PR patients but not for those with SD/PD. CONCLUSIONS: This study emphasizes the importance of IC response in LANPC and highlights the potential benefits of nimotuzumab during CCRT for improving survival outcomes in CR/PR patients. Tailored treatment approaches for SD/PD patients warrant further investigation.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Quimioradioterapia , Quimioterapia de Inducción , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , Femenino , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/patología , Quimioradioterapia/métodos , Quimioterapia de Inducción/métodos , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Estudios Retrospectivos , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/tratamiento farmacológico , Adulto , Anciano , Estadificación de Neoplasias , Resultado del Tratamiento , Estimación de Kaplan-Meier , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivencia sin Enfermedad , Adulto Joven
3.
ACS Omega ; 9(30): 32268-32286, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39100297

RESUMEN

Skin is the first defense barrier of the human body, which can resist the invasion of external dust, microorganisms and other pollutants, and ensure that the human body maintains the homeostasis of the internal environment. Once the skin is damaged, the health threat to the human body will increase. Wound repair and the human internal environment are a dynamic process. How to effectively accelerate the healing of wounds without affecting the internal environment of the human body and guarantee that the repaired tissue retains its original function as much as possible has become a research hotspot. With the advancement of technology, researchers have combined new technologies to develop and prepare various types of materials for wound healing. This article will introduce the wound repair materials developed and prepared in recent years from three types: nanofibers, composite hydrogels, and other new materials. The paper aims to provide reference for researchers in related fields to develop and prepare multifunctional materials. This may be helpful to design more ideal materials for clinical application, and then achieve better wound healing and regeneration effects.

4.
Ann Med ; 56(1): 2383959, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39086168

RESUMEN

BACKGROUND: The therapeutic benefit of concurrent chemoradiotherapy (CCRT) in elderly nasopharyngeal carcinoma (NPC) patients remains controversial. This study aimed to investigate the efficacy and toxicity of lobaplatin-based CCRT in elderly patients with NPC. METHODS: We included stage II-IVA NPC patients aged ≥65 years who received lobaplatin concomitant with intensity-modulated radiation therapy (IMRT) between March 2019 and January 2023. Objective response rates and treatment-related toxicity were assessed. Kaplan-Meier's analysis was performed to calculate survival rates. RESULTS: A total of 29 patients were included with a median age of 67 years. There were 19 patients (65.5%) who had comorbidities. All patients had serum EBV-DNA detective before treatment; the median EBV-DNA load was 236 IU/mL. There were 25 (86.2%) patients treated with induction chemotherapy, and the overall response rate was 92.0%. All patients received IMRT and concurrent chemotherapy with lobaplatin. During the CCRT, the most common adverse effect was haematological toxicity. Three patients (10.3%) had grade 3 leucopenia, three patients (10.3%) had grade 3 neutropenia, and eight patients (27.6%) had grade 3-4 thrombocytopenia. The rate of grade 3 mucositis was 34.5%. No patients had liver and kidney dysfunction. The median weight loss was 4 kg during CCRT. After three months of CCRT, the total response rate was 100%. EBV-DNA was not detected in any patients. The median follow-up was 32.1 months. The 3-year locoregional recurrence-free survival, distant metastasis-free survival, progression-free survival and overall survival were 95.8%, 85.7%, 82.5% and 100%, respectively. CONCLUSIONS: Lobaplatin-based CCRT is safe and feasible for elderly NPC patients, with satisfactory short-term survival outcomes and acceptable toxicities. A phase 2 trial is ongoing to investigate the role of lobaplatin-based CCRT on long-term survival and treatment toxicities for this population.


Asunto(s)
Quimioradioterapia , Ciclobutanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Compuestos Organoplatinos , Radioterapia de Intensidad Modulada , Humanos , Masculino , Anciano , Femenino , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/mortalidad , Ciclobutanos/uso terapéutico , Ciclobutanos/administración & dosificación , Ciclobutanos/efectos adversos , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Compuestos Organoplatinos/uso terapéutico , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/tratamiento farmacológico , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/administración & dosificación , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Estimación de Kaplan-Meier
5.
Molecules ; 29(15)2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39124939

RESUMEN

The detection of pathogens in medical wastewater is crucial due to the high content of pathogenic microorganisms that pose significant risks to public health and the environment. Medical wastewater, which includes waste from infectious disease and tuberculosis facilities, as well as comprehensive medical institutions, contains a variety of pathogens such as bacteria, viruses, fungi, and parasites. Traditional detection methods like nucleic acid detection and immunological assays, while effective, are often time-consuming, expensive, and not suitable for rapid detection in underdeveloped areas. Electrochemical biosensors offer a promising alternative with advantages including simplicity, rapid response, portability, and low cost. This paper reviews the sources of pathogens in medical wastewater, highlighting specific bacteria (e.g., E. coli, Salmonella, Staphylococcus aureus), viruses (e.g., enterovirus, respiratory viruses, hepatitis virus), parasites, and fungi. It also discusses various electrochemical biosensing techniques such as voltammetry, conductometry, impedance, photoelectrochemical, and electrochemiluminescent biosensors. These technologies facilitate the rapid, sensitive, and specific detection of pathogens, thereby supporting public health and environmental safety. Future research may should pay more attention on enhancing sensor sensitivity and specificity, developing portable and cost-effective devices, and innovating detection methods for diverse pathogens to improve public health protection and environmental monitoring.


Asunto(s)
Técnicas Biosensibles , Técnicas Electroquímicas , Aguas Residuales , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Aguas Residuales/virología , Aguas Residuales/microbiología , Aguas Residuales/análisis , Virus/aislamiento & purificación , Bacterias/aislamiento & purificación , Humanos , Monitoreo del Ambiente/métodos , Hongos/aislamiento & purificación
6.
PLoS One ; 19(8): e0308673, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39137209

RESUMEN

OBJECTIVE: Relative to explicit absenteeism, nurses' presenteeism has a more lasting impact and is more harmful and costly. This study aimed to explore the relationship between work-family conflict, perceived social support, and presenteeism and whether perceived social support mediates the relationship between work-family conflict and presenteeism among ICU nurses working on shifts in Chinese public hospitals. MATERIALS AND METHODS: A cross-sectional research design was conducted from January to April 2023 in Sichuan Province, China. A total of 609 valid questionnaires were collected. The questionnaires contained information on demographic characteristics, the Work-Family Conflict (WFC) scale, the Perceived Social Support Scale (PSSS), and Stanford Presenteeism Scale-6 (SPS-6). Multiple stratified regression was used to explore the mediating role of perceived social support between work-family conflict and presenteeism. The mediating effect of perceived social support in work-family conflict and presenteeism was tested by Model 4 in the PROCESS 4.1 macro program in SPSS. RESULTS: A total of 609 nurses were included in this study, and the mean presenteeism score for ICU nurses working on shifts was 16.01 ± 4.293 (Mean ± SD), with high presenteeism accounting for 58.46%. After controlling for sociodemographic characteristic variables, work-family conflict was positively associated with presenteeism, explaining 7.7% of the variance. High perceived social support was related to low presenteeism, explaining 11.5% of the variance. Perceived social support mediated the association between work-family conflict and presenteeism among ICU nurses working on shifts. CONCLUSIONS: Chinese shift-work ICU nurses' high presenteeism scores deserve managers' attention. Work-family conflict is a significant predictor of nurses' presenteeism. Perceived social support is essential in improving nurses' work-family conflict and mediates the relationship between work-family conflict and presenteeism. Improving social support can reduce the impact of work-family conflict on presenteeism among nurses working shifts.


Asunto(s)
Hospitales Públicos , Unidades de Cuidados Intensivos , Presentismo , Apoyo Social , Humanos , Femenino , Adulto , Estudios Transversales , Masculino , Presentismo/estadística & datos numéricos , China , Encuestas y Cuestionarios , Personal de Enfermería en Hospital/psicología , Personal de Enfermería en Hospital/estadística & datos numéricos , Persona de Mediana Edad , Enfermería de Cuidados Críticos , Enfermeras y Enfermeros/psicología , Familia/psicología
7.
Artículo en Inglés | MEDLINE | ID: mdl-39145784

RESUMEN

PURPOSE: Somatostatin Receptor 2 (SSTR2)-targeted radiopharmaceutical [68Ga]Ga-DOTATATE has potential advantages in the diagnosis of nasopharyngeal carcinoma (NPC). This study introduces a novel long-lasting SSTR2 analogue, LNC1010, based on DOTATATE, a truncated Evans blue-binding moiety, and a polyethylene-glycol linker. We hypothesised that peptide receptor radionuclide therapy (PRRT) is more effective with [177Lu]Lu-LNC1010 than with [177Lu]Lu-DOTATATE in treating metastatic NPC. METHODS: We assessed binding characteristics of LNC1010 in vitro using C666-1 NPC cells and in-vivo pharmacokinetics of [68Ga]Ga/[177Lu]Lu-LNC1010 in C666-1 NPC xenografts via PET and SPECT imaging, biodistribution studies, and PRRT, and compared them with [68Ga]Ga/[177Lu] Lu-labelled DOTATATE. Furthermore, a proof-of-concept approach for imaging and therapy was conducted in a patient with metastatic NPC. RESULTS: LNC1010 exhibited strong uptake and specific affinity for SSTR2 in C666-1 NPC cells. PET and SPECT imaging demonstrated higher uptake and longer tumour retention of [68Ga]Ga/[177Lu]Lu-LNC1010 than [68Ga]Ga/[177Lu]Lu-DOTATATE in C666-1 NPC xenografts, indicating its suitability for PRRT applications in NPCs. Biodistribution studies confirmed the higher uptake and prolonged retention of [177Lu]Lu-LNC1010 than [177Lu]Lu-DOTATATE. In preclinical PRRT studies, [177Lu]Lu-LNC1010 showed greater inhibition of tumour growth in C666-1 NPC xenografts than [177Lu]Lu-DOTATATE. In a subsequent pilot clinical study, PRRT with [177Lu]Lu-LNC1010 achieved favourable therapeutic and negligible side effects in a patient with metastatic NPC. CONCLUSION: [177Lu]Lu-LNC1010 demonstrated increased tumour uptake and prolonged retention in SSTR2-positive NPCs, with superior anti-tumour efficacy to that of [177Lu]Lu-DOTATATE in preclinical studies. These findings suggest that PRRT with [177Lu]Lu-LNC1010 is a promising treatment for advanced NPC, extending the clinical scope of PRRT beyond neuroendocrine tumours.

9.
Appl Environ Microbiol ; : e0085024, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39016614

RESUMEN

Viral communities exist in a variety of ecosystems and play significant roles in mediating biogeochemical processes, whereas viruses inhabiting strongly alkaline geochemical systems remain underexplored. In this study, the viral diversity, potential functionalities, and virus-host interactions in a strongly alkaline environment (pH = 10.4-12.4) exposed to the leachates derived from the serpentinization-like reactions of smelting slags were investigated. The viral populations (e.g., Herelleviridae, Queuovirinae, and Inoviridae) were closely associated with the dominating prokaryotic hosts (e.g., Meiothermus, Trueperaceae, and Serpentinomonas) in this ultrabasic environment. Auxiliary metabolic genes (AMGs) suggested that viruses may enhance hosts' fitness by facilitating cofactor biosynthesis, hydrogen metabolism, and carbon cycling. To evaluate the activity of synthesis of essential cofactor vitamin B9 by the viruses, a viral folA (vfolA) gene encoding dihydrofolate reductase (DHFR) was introduced into a thymidine-auxotrophic strain Escherichia coli MG1655 ΔfolA mutant, which restored the growth of the latter in the absence of thymidine. Notably, the homologs of the validated vDHFR were globally distributed in the viromes across various ecosystems. The present study sheds new light on the unique viral communities in hyperalkaline ecosystems and their potential beneficial impacts on the coexisting microbial consortia by supplying essential cofactors. IMPORTANCE: This study presents a comprehensive investigation into the diversity, potential functionalities, and virus-microbe interactions in an artificially induced strongly alkaline environment. Functional validation of the detected viral folA genes encoding dihydrofolate reductase substantiated the synthesis of essential cofactors by viruses, which may be ubiquitous, considering the broad distribution of the viral genes associated with folate cycling.

10.
iScience ; 27(6): 109888, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38947517

RESUMEN

Stem cell therapy for intrauterine adhesions (IUAs) has been widely used in clinical treatment. However, intravenous injection lacks sufficient targeting capabilities, while in situ injection poses challenges in ensuring the effective survival of stem cells. Furthermore, the mechanism underlying the interaction between stem cells and endometrial cells in vivo remains poorly understood, and there is a lack of suitable in vitro models for studying these problems. Here, we designed an extracellular matrix (ECM)-adhesion mimic hydrogel for intrauterine administration, which was more effective than direct injection in treating IUAs. Additionally, we analyzed the epithelial-mesenchymal transition (EMT) and confirmed that the activation of endometrial epithelial stem cells is pivotal. Our findings demonstrated that umbilical cord mesenchymal stem cells (UC-MSCs) secrete WNT7A to activate endometrial epithelial stem cells, thereby accelerating regeneration of the endometrial epithelium. Concurrently, under transforming growth factor alpha (TGFA) stimulation secreted by the EMT epithelium, UC-MSCs upregulate E-cadherin while partially implanting into the endometrial epithelium.

11.
Signal Transduct Target Ther ; 9(1): 148, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38890298

RESUMEN

Penpulimab is an anti-programmed cell death-1 (PD-1) IgG1 antibody with no Fc gamma receptor (FcγR) binding activity, and thus theoretically reduced immune-related adverse events (irAEs) while maintaining efficacy. This single-arm, phase II trial conducted across 20 tertiary care centers in China enrolled adult patients with metastatic nasopharyngeal carcinoma (NPC) who had failed two or more lines of previous systemic chemotherapy. Patients received 200-mg penpulimab intravenously every 2 weeks (4 weeks per cycle) until disease progression or intolerable toxicities. The primary endpoint was objective response rate (ORR) per RECIST (version 1.1), as assessed by an independent radiological review committee. The secondary endpoints included progression-free survival (PFS) and overall survival (OS). One hundred thirty patients were enrolled and 125 were efficacy evaluable. At the data cutoff date (September 28, 2022), 1 patient achieved complete response and 34 patients attained partial response. The ORR was 28.0% (95% CI 20.3-36.7%). The response was durable, with 66.8% still in response at 9 months. Thirty-three patients (26.4%) were still on treatment. The median PFS and OS were 3.6 months (95% CI = 1.9-7.3 months) and 22.8 months (95% CI = 17.1 months to not reached), respectively. Ten (7.6%) patients experienced grade 3 or higher irAEs. Penpulimab has promising anti-tumor activities and acceptable toxicities in heavily pretreated metastatic NPC patients, supporting further clinical development as third-line treatment of metastatic NPC.


Asunto(s)
Carcinoma Nasofaríngeo , Metástasis de la Neoplasia , Receptor de Muerte Celular Programada 1 , Humanos , Masculino , Persona de Mediana Edad , Femenino , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/patología , Adulto , Anciano , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos
12.
Clin Chem Lab Med ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38915251

RESUMEN

INTRODUCTION: The correlation between serum angiopoietin-2 levels and acute kidney injury (AKI) is a topic of significant clinical interest. This meta-analysis aims to provide a comprehensive evaluation of this relationship. CONTENT: A systematic search was conducted in PubMed, Embase, Web of Science, and Cochrane databases up to October 11, 2023. The included studies were evaluated using the Newcastle-Ottawa Scale (NOS) and Methodological Index for Non-Randomized Studies (MINORS). Weighted mean differences (WMD) and odds ratios (OR) were calculated using random-effects models. Sensitivity analysis, funnel plots, and Egger's test were used to assess the robustness and publication bias of the findings. Subgroup analyses were performed to explore potential variations between adults and children. SUMMARY: Eighteen studies encompassing a total of 7,453 participants were included. The analysis revealed a significant elevation in serum angiopoietin-2 levels in patients with AKI compared to those without (WMD: 4.85; 95 % CI: 0.75 to 0.27; I²=93.2 %, p<0.001). Subgroup analysis indicated significantly higher angiopoietin-2 levels in adults with AKI (WMD: 5.17; 95 % CI: 3.51 to 6.83; I²=82.6 %, p<0.001), but not in children. Additionally, high serum angiopoietin-2 levels were associated with an increased risk of AKI (OR: 1.58; 95 % CI: 1.39 to 1.8; I²=89.1 %, p<0.001). Sensitivity analysis validated the robustness of these results, showing no substantial change in the overall effect size upon the exclusion of individual studies. OUTLOOK: This meta-analysis supports a significant association between elevated serum angiopoietin-2 levels and increased risk of AKI. The observed differential association between adults and children highlights the need for further targeted research to understand these age-specific variations.

13.
Signal Transduct Target Ther ; 9(1): 142, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38825657

RESUMEN

Radiotherapy combined with immune checkpoint blockade holds great promise for synergistic antitumor efficacy. Targeted radionuclide therapy delivers radiation directly to tumor sites. LNC1004 is a fibroblast activation protein (FAP)-targeting radiopharmaceutical, conjugated with the albumin binder Evans Blue, which has demonstrated enhanced tumor uptake and retention in previous preclinical and clinical studies. Herein, we demonstrate that 68Ga/177Lu-labeled LNC1004 exhibits increased uptake and prolonged retention in MC38/NIH3T3-FAP and CT26/NIH3T3-FAP tumor xenografts. Radionuclide therapy with 177Lu-LNC1004 induced a transient upregulation of PD-L1 expression in tumor cells. The combination of 177Lu-LNC1004 and anti-PD-L1 immunotherapy led to complete eradication of all tumors in MC38/NIH3T3-FAP tumor-bearing mice, with mice showing 100% tumor rejection upon rechallenge. Immunohistochemistry, single-cell RNA sequencing (scRNA-seq), and TCR sequencing revealed that combination therapy reprogrammed the tumor microenvironment in mice to foster antitumor immunity by suppressing malignant progression and increasing cell-to-cell communication, CD8+ T-cell activation and expansion, M1 macrophage counts, antitumor activity of neutrophils, and T-cell receptor diversity. A preliminary clinical study demonstrated that 177Lu-LNC1004 was well-tolerated and effective in patients with refractory cancers. Further, scRNA-seq of peripheral blood mononuclear cells underscored the importance of addressing immune evasion through immune checkpoint blockade treatment. This was emphasized by the observed increase in antigen processing and presentation juxtaposed with T cell inactivation. In conclusion, our data supported the efficacy of immunotherapy combined with 177Lu-LNC1004 for cancer patients with FAP-positive tumors.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Animales , Ratones , Inhibidores de Puntos de Control Inmunológico/farmacología , Humanos , Proteínas de la Membrana/genética , Proteínas de la Membrana/inmunología , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Endopeptidasas/genética , Células 3T3 NIH , Radiofármacos/uso terapéutico , Serina Endopeptidasas/genética , Serina Endopeptidasas/inmunología , Ensayos Antitumor por Modelo de Xenoinjerto , Inmunoterapia , Gelatinasas/genética , Gelatinasas/inmunología , Lutecio/farmacología , Línea Celular Tumoral
14.
Mol Pharm ; 21(7): 3684-3692, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38899595

RESUMEN

Early detection of pulmonary fibrosis is a critical yet insufficiently met clinical necessity. This study evaluated the effectiveness of FAPI-LM3, a 68Ga-radiolabeled heterobivalent molecular probe that targets fibroblast activating protein (FAP) and somatostatin receptor 2 (SSTR2), in the early detection of pulmonary fibrosis, leveraging its potential for early disease identification. A bleomycin-induced early pulmonary fibrosis model was established in C57BL/6 mice for 7 days. FAP and SSTR2 expression levels were quantitatively assessed in human idiopathic pulmonary fibrosis lung tissue samples and bleomycin-treated mouse lung tissues by using western blotting, real-time quantitative PCR (RT-qPCR), and immunofluorescence techniques. The diagnostic performance of FAPI-LM3 was investigated by synthesizing monomeric radiotracers 68Ga-FAPI-46 and 68Ga-DOTA-LM3 alongside the heterobivalent probe 68Ga-FAPI-LM3. These imaging radiopharmaceuticals were used in small-animal PET to compare their uptake in fibrotic and normal lung tissues. Results indicated significant upregulation of FAP and SSTR2 at both RNA and protein levels in fibrotic lung tissues compared with that in normal controls. PET imaging demonstrated significantly enhanced uptake of the 68Ga-FAPI-LM3 probe in fibrotic lung tissues, with superior visual effects compared to monomeric tracers. At 60 min postinjection, early stage fibrotic tissues (day 7) demonstrated low-to-medium uptake of monomeric probes, including 68Ga-DOTA-LM3 (0.45 ± 0.04% ID/g) and 68Ga-FAPI-46 (0.78 ± 0.09% ID/g), whereas the uptake of the heterobivalent probe 68Ga-FAPI-LM3 (1.90 ± 0.10% ID/g) was significantly higher in fibrotic lesions than in normal lung tissue. Blockade experiments confirmed the specificity of 68Ga-FAPI-LM3 uptake, which was attributed to synergistic targeting of FAP and SSTR2. This study demonstrates the potential of 68Ga-FAPI-LM3 for early pulmonary fibrosis detection via molecular imaging, offering significant benefits over monomeric tracers 68Ga-FAPI-46 and 68Ga-DOTA-LM3. This strategy offers new possibilities for noninvasive and precise early detection of pulmonary fibrosis.


Asunto(s)
Radioisótopos de Galio , Ratones Endogámicos C57BL , Tomografía de Emisión de Positrones , Radiofármacos , Receptores de Somatostatina , Animales , Ratones , Receptores de Somatostatina/metabolismo , Humanos , Tomografía de Emisión de Positrones/métodos , Radiofármacos/farmacocinética , Radiofármacos/química , Fibrosis Pulmonar/diagnóstico por imagen , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/inducido químicamente , Pulmón/diagnóstico por imagen , Pulmón/patología , Pulmón/metabolismo , Masculino , Bleomicina , Endopeptidasas/metabolismo , Modelos Animales de Enfermedad , Femenino , Fibrosis Pulmonar Idiopática/diagnóstico por imagen , Fibrosis Pulmonar Idiopática/metabolismo , Proteínas de la Membrana/metabolismo , Serina Endopeptidasas/metabolismo , Quinolinas
15.
BMC Health Serv Res ; 24(1): 653, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773420

RESUMEN

BACKGROUND: Implicit absenteeism is very common among nurses. Poor perceived social support of intensive care unit nurses has a negative impact on their mental and physical health. There is evidence that lack of occupational coping self-efficacy can promote implicit absenteeism; however, the relationship between lack of occupational coping self-efficacy in perceived social support and implicit absenteeism of intensive care unit nurses is unclear. Therefore, this study aimed to evaluate the role of perceived social support between lack of occupational coping self-efficacy and implicit absenteeism of intensive care unit nurses, and to provide reliable evidence to the management of clinical nurses. METHODS: A cross-sectional study of 517 intensive care unit nurses in 10 tertiary hospitals in Sichuan province, China was conducted, of which 474 were valid questionnaires with a valid recovery rate of 91.6%. The survey tools included the Chinese version of Implicit Absenteeism Scale, the Chinese version of Perceived Social Support Scale, the Chinese version of Occupational Coping Self-Efficacy Scale and the Sociodemographic characteristics. Descriptive analysis and Pearson correlation analysis were performed using SPSS version 22.0, while the mediating effects were performed using AMOS version 24.0. RESULTS: The average of intensive care unit nurses had a total implicit absenteeism score of (16.87 ± 3.98), in this study, the median of intensive care unit nurses' implicit absenteeism score was 17, there were 210 intensive care unit nurses with low implicit absenteeism (44.3%) and 264 ICU nurses with high implicit absenteeism (55.7%). A total perceived social support score of (62.87 ± 11.61), and a total lack of occupational coping self-efficacy score of (22.78 ± 5.98). The results of Pearson correlation analysis showed that implicit absenteeism was negatively correlated with perceived social support (r = -0.260, P < 0.001) and positively correlated with lack of occupational coping self-efficacy (r = 0.414, P < 0.001). In addition, we found that perceived social support plays a mediating role in lack of occupational coping self-efficacy and implicit absenteeism [ß = 0.049, 95% CI of (0.002, 0.101)]. CONCLUSIONS: Intensive care unit nurses had a high level of implicit absenteeism with a moderate level of perceived social support and lack of occupational coping self-efficacy. Nursing managers should pay attention to the nurses those who were within low levels of social support and negative coping strategies, and take measures to reduce intensive care unit nurses' professional stress, minimize implicit absenteeism.


Asunto(s)
Absentismo , Adaptación Psicológica , Unidades de Cuidados Intensivos , Autoeficacia , Apoyo Social , Humanos , Estudios Transversales , Femenino , Masculino , Adulto , China , Encuestas y Cuestionarios , Personal de Enfermería en Hospital/psicología , Persona de Mediana Edad , Enfermería de Cuidados Críticos
16.
J Genet Genomics ; 51(8): 844-854, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38575112

RESUMEN

Pathological myocardial hypertrophy is a common early clinical manifestation of heart failure, with noncoding RNAs exerting regulatory influence. However, the molecular function of circular RNAs (circRNAs) in the progression from cardiac hypertrophy to heart failure remains unclear. To uncover functional circRNAs and identify the core circRNA signaling pathway in heart failure, we construct a global triple network (microRNA, circRNA, and mRNA) based on the competitive endogenous RNA (ceRNA) theory. We observe that cardiac hypertrophy-related circRNA (circRNA CHRC), within the ceRNA network, is down-regulated in both transverse aortic constriction mice and Ang-II--treated primary mouse cardiomyocytes. Silencing circRNA CHRC increases cross-sectional cell area, atrial natriuretic peptide, and ß-myosin heavy chain levels in primary mouse cardiomyocytes. Further screening shows that circRNA CHRC targets the miR-431-5p/KLF15 axis implicated in heart failure progression in vivo and in vitro. Immunoprecipitation with anti-Ago2-RNA confirms the interaction between circRNA CHRC and miR-431-5p, while miR-431-5p mimics reverse Klf15 activation caused by circRNA CHRC overexpression. In summary, circRNA CHRC attenuates cardiac hypertrophy via sponging miR-431-5p to maintain the normal level of Klf15 expression.


Asunto(s)
Insuficiencia Cardíaca , Factores de Transcripción de Tipo Kruppel , MicroARNs , Miocitos Cardíacos , ARN Circular , Transducción de Señal , MicroARNs/genética , MicroARNs/metabolismo , Animales , ARN Circular/genética , ARN Circular/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/metabolismo , Ratones , Transducción de Señal/genética , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Progresión de la Enfermedad , Humanos , Cardiomegalia/genética , Cardiomegalia/patología , Cardiomegalia/metabolismo , ARN/genética , ARN/metabolismo , Masculino , Regulación de la Expresión Génica/genética
17.
J Cancer ; 15(7): 2066-2073, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38434985

RESUMEN

Background: There are few effective prediction models for intermediate-stage hepatocellular carcinoma (IM-HCC) patients treated with transarterial chemoembolization (TACE) to predict overall survival (OS) is available. The learning survival neural network (DeepSurv) was developed to showed a better performance than cox proportional hazards model in prediction of OS. This study aimed to develop a deep learning-based prediction model to predict individual OS. Methods: This multicenter, retrospective, cohort study examined data from the electronic medical record system of four hospitals in China between January 1, 2007, to December 31, 2016. Patients were divided into a training set(n=1075) and a test set(n=269) at a ratio of 8:2 to develop a deep learning-based algorithm (deepHAP IV). The deepHAP IV model was externally validated on an independent cohort(n=414) from the other three centers. The concordance index, the area under the receiver operator characteristic curves, and the calibration curve were used to assess the performance of the models. Results: The deepHAP IV model had a c-index of 0.74, whereas AUROC for predicting survival outcomes of 1-, 3-, and 5-year reached 0.80, 0.76, and 0.74 in the training set. Calibration graphs showed good consistency between the actual and predicted OS in the training set and the validation cohort. Compared to the other five Cox proportional-hazards models, the model this study conducted had a better performance. Patients were finally classified into three groups by X-tile plots with predicted 3-year OS rate (low: ≤ 0.11; middle: > 0.11 and ≤ 0.35; high: >0.35). Conclusion: The deepHAP IV model can effectively predict the OS of patients with IM-HCC, showing a better performance than previous Cox proportional hazards models.

18.
Oral Oncol ; 151: 106723, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38387261

RESUMEN

OBJECTIVE: This study was designed to assess the efficacy and safety of cadonilimab monotherapy, a first-in-class, bi-specific PD-1/CTLA-4 antibody, in patients with previously treated recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). PATIENTS AND METHODS: This multicenter, open-label, single-arm, phase II clinical trial enrolled patients with R/M-NPC who had failed first-line platinum-based chemotherapy and second-line single agent or combined chemotherapy, and immunotherapy-naive. Patients received cadonilimab for 6 mg/kg once every 2 weeks (Q2W). The primary endpoint was objective response rate (ORR) in full analysis set (FAS) assessed by investigators according to RECIST v.1.1. The secondary endpoint included progression-free survival (PFS), overall survival (OS), duration of response (DoR), time to response (TTR) and safety. RESULTS: A total of 23 patients were assessed. The median time from first dose to data cutoff was 16.56 (range, 0.8-25.2) months. ORR was 26.1 % (95 %CI:10.2-48.4). The ORR were 44.4 % (95 %CI: 13.7-78.8) and 14.3 % (95 %CI:1.8-42.8) in patients with tumor PD-L1 expression ≥50 % and <50 %, respectively. ORR was achieved in 40.0 % (95 %CI:12.2-73.8) of patients with EBV-DNA level <4000 IU/ml (n = 10) and 15.4 % (95 %CI:1.9-45.4) of those with ≥4000 IU/ml. The median PFS was 3.71 months (95 %CI: 1.84-9.30). respectively. Median OS was not reached, and the 12-month OS rate was 79.7 % (95 % CI:54.5-91.9). Only two patients (8.3 %) experienced Grade ≥3 treatment-related adverse events (TRAEs) with hypothyroidism (30.4 %), rash (21.7 %) and pruritus (21.7 %) being the most prevalent TRAEs. CONCLUSION: Cadonilimab monotherapy demonstrated a promising efficacy and manageable toxicity in patients with previously treated R-M/NPC and provide an efficacious salvage treatment option.


Asunto(s)
Neoplasias Nasofaríngeas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Nasofaríngeo/tratamiento farmacológico , Neoplasias Nasofaríngeas/patología , Supervivencia sin Progresión , Resultado del Tratamiento
19.
Plant Divers ; 46(1): 70-77, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38343594

RESUMEN

Here, we characterize the temporal and spatial dynamics of forest community structure and species diversity in a subtropical evergreen broad-leaved forest in China. We found that community structure in this forest changed over a 15-year period. Specifically, renewal and death of common species was large, with the renewal of individuals mainly concentrated within a few populations, especially those of Aidia canthioides and Cryptocarya concinna. The numbers of individual deaths for common species were concentrated in the small and mid-diameter level. The spatial distribution of community species diversity fluctuated in each monitoring period, showing a more dispersed diversity after the 15-year study period, and the coefficient of variation on quadrats increased. In 2010, the death and renewal of the community and the spatial variation of species diversity were different compared to other survey years. Extreme weather may have affected species regeneration and community stability in our subtropical monsoon evergreen broad-leaved forests. Our findings suggest that strengthening the monitoring and management of the forest community will help better understand the long- and short-term causes of dynamic fluctuations of community structure and species diversity, and reveal the factors that drive changes in community structure.

20.
Diabetes Res Clin Pract ; 209: 111570, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38341040

RESUMEN

AIMS: To examine whether sleep health in the first trimester could predict glucose metabolism in the second trimester. METHODS: Pregnant women (N = 127) during the first trimester were recruited (August 2022 to March 2023). Overall sleep health was assessed by the Sleep Health Index. Various dimensions of sleep health were measured using a 7-day sleep diary and questionnaires. The outcomes, including diagnosis of gestational diabetes mellitus (GDM) and HbA1c, were obtained from the medical records in the second trimester. Poisson regression analysis and multiple linear regression were used for data analysis. RESULTS: The average age of the participants was 32.6 years. The incidence of GDM was 28.3 % and the mean HbA1c was 5.2 % (33 mmol/mol). Sleep duration regularity (RR = 1.808; 95 %CI 1.023, 3.196) was associated with GDM after controlling for confounders. SHI total score (ß = -0.278; 95 %CI -0.022, -0.005) and sleep duration regularity (ß = 0.243; 95 %CI 0.057, 0.372) were associated with HbA1c. CONCLUSIONS: Worse sleep health, particularly lower sleep regularity, predicted worse glucose metabolism among pregnant women. Healthcare professional may consider adding sleep-related assessment to prenatal care. Maintaining regular sleep should be encouraged. Studies examining the impact of sleep intervention on glucose metabolism among pregnant women are warranted.


Asunto(s)
Diabetes Gestacional , Mujeres Embarazadas , Embarazo , Humanos , Femenino , Adulto , Hemoglobina Glucada , Estudios Prospectivos , Diabetes Gestacional/epidemiología , Diabetes Gestacional/diagnóstico , Primer Trimestre del Embarazo , Sueño , Glucosa , Glucemia/metabolismo
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