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1.
Front Med (Lausanne) ; 11: 1391907, 2024.
Article in English | MEDLINE | ID: mdl-39086941

ABSTRACT

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.
Article in English | MEDLINE | ID: mdl-39095737

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal, Humanized , Chemoradiotherapy , Induction Chemotherapy , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , Male , Female , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/mortality , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/pathology , Chemoradiotherapy/methods , Induction Chemotherapy/methods , Middle Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Retrospective Studies , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/drug therapy , Adult , Aged , Neoplasm Staging , Treatment Outcome , Kaplan-Meier Estimate , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Disease-Free Survival , Young Adult
3.
Ann Med ; 56(1): 2383959, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39086168

ABSTRACT

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.


Subject(s)
Chemoradiotherapy , Cyclobutanes , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Organoplatinum Compounds , Radiotherapy, Intensity-Modulated , Humans , Male , Aged , Female , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/mortality , Cyclobutanes/therapeutic use , Cyclobutanes/administration & dosage , Cyclobutanes/adverse effects , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Organoplatinum Compounds/therapeutic use , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/drug therapy , Radiotherapy, Intensity-Modulated/adverse effects , Radiotherapy, Intensity-Modulated/methods , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/adverse effects , Antineoplastic Agents/administration & dosage , Retrospective Studies , Survival Rate , Treatment Outcome , Kaplan-Meier Estimate
5.
Appl Environ Microbiol ; : e0085024, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39016614

ABSTRACT

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.

6.
iScience ; 27(6): 109888, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38947517

ABSTRACT

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.

7.
Signal Transduct Target Ther ; 9(1): 142, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38825657

ABSTRACT

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.


Subject(s)
Immune Checkpoint Inhibitors , Animals , Mice , Immune Checkpoint Inhibitors/pharmacology , Humans , Membrane Proteins/genetics , Membrane Proteins/immunology , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology , Endopeptidases/genetics , NIH 3T3 Cells , Radiopharmaceuticals/therapeutic use , Serine Endopeptidases/genetics , Serine Endopeptidases/immunology , Xenograft Model Antitumor Assays , Immunotherapy , Gelatinases/genetics , Gelatinases/immunology , Lutetium/pharmacology , Cell Line, Tumor
8.
Clin Chem Lab Med ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38915251

ABSTRACT

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.

9.
Mol Pharm ; 21(7): 3684-3692, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38899595

ABSTRACT

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.


Subject(s)
Gallium Radioisotopes , Mice, Inbred C57BL , Positron-Emission Tomography , Radiopharmaceuticals , Receptors, Somatostatin , Animals , Mice , Receptors, Somatostatin/metabolism , Humans , Positron-Emission Tomography/methods , Radiopharmaceuticals/pharmacokinetics , Radiopharmaceuticals/chemistry , Pulmonary Fibrosis/diagnostic imaging , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/chemically induced , Lung/diagnostic imaging , Lung/pathology , Lung/metabolism , Male , Bleomycin , Endopeptidases/metabolism , Disease Models, Animal , Female , Idiopathic Pulmonary Fibrosis/diagnostic imaging , Idiopathic Pulmonary Fibrosis/metabolism , Membrane Proteins/metabolism , Serine Endopeptidases/metabolism , Quinolines
10.
Signal Transduct Target Ther ; 9(1): 148, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38890298

ABSTRACT

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.


Subject(s)
Nasopharyngeal Carcinoma , Neoplasm Metastasis , Programmed Cell Death 1 Receptor , Humans , Male , Middle Aged , Female , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/pathology , Adult , Aged , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/immunology , Antibodies, Monoclonal, Humanized/therapeutic use , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/pathology , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/adverse effects
11.
BMC Health Serv Res ; 24(1): 653, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773420

ABSTRACT

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.


Subject(s)
Absenteeism , Adaptation, Psychological , Intensive Care Units , Self Efficacy , Social Support , Humans , Cross-Sectional Studies , Female , Male , Adult , China , Surveys and Questionnaires , Nursing Staff, Hospital/psychology , Middle Aged , Critical Care Nursing
12.
J Genet Genomics ; 51(8): 844-854, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38575112

ABSTRACT

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.


Subject(s)
Heart Failure , Kruppel-Like Transcription Factors , MicroRNAs , Myocytes, Cardiac , RNA, Circular , Signal Transduction , MicroRNAs/genetics , MicroRNAs/metabolism , Animals , RNA, Circular/genetics , RNA, Circular/metabolism , Kruppel-Like Transcription Factors/genetics , Kruppel-Like Transcription Factors/metabolism , Heart Failure/genetics , Heart Failure/pathology , Heart Failure/metabolism , Mice , Signal Transduction/genetics , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Disease Progression , Humans , Cardiomegaly/genetics , Cardiomegaly/pathology , Cardiomegaly/metabolism , RNA/genetics , RNA/metabolism , Male , Gene Expression Regulation/genetics
13.
J Cancer ; 15(7): 2066-2073, 2024.
Article in English | MEDLINE | ID: mdl-38434985

ABSTRACT

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.

14.
Oral Oncol ; 151: 106723, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38387261

ABSTRACT

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.


Subject(s)
Nasopharyngeal Neoplasms , Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Neoplasms/pathology , Progression-Free Survival , Treatment Outcome
15.
Diabetes Res Clin Pract ; 209: 111570, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38341040

ABSTRACT

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.


Subject(s)
Diabetes, Gestational , Pregnant Women , Pregnancy , Humans , Female , Adult , Glycated Hemoglobin , Prospective Studies , Diabetes, Gestational/epidemiology , Diabetes, Gestational/diagnosis , Pregnancy Trimester, First , Sleep , Glucose , Blood Glucose/metabolism
16.
Front Psychol ; 15: 1347249, 2024.
Article in English | MEDLINE | ID: mdl-38356774

ABSTRACT

Background: Nurses are the largest occupational group in the health field, with inestimable value in realizing universal health coverage, and nurses' physical and mental health has become an ordinary global reality. Compared with explicit absence, nurses' presenteeism has a more lasting impact and significant harm and loss. It has become an essential factor affecting nurses' physical and mental health, declining quality of healthcare services, and elevated healthcare-related risks. There is a lack of research exploring whether occupational coping self-efficacy influences nurses' presenteeism behavior, especially in less-developed regions of China. Objective: This study aimed to investigate the current status of ICU nurses' occupational coping self-efficacy and presenteeism in public hospitals in western China and to explore the impact of ICU nurses' occupational coping self-efficacy on presenteeism. Methods: A cross-sectional research design selected 722 ICU nurses in western China from January to February 2023 as survey respondents. A general information questionnaire, Occupational Coping Self-Efficacy Scale (OCSE-N), and Stanford Presenteeism Scale (SPS-6) were used. SPSS 21.0 software was used for statistical analysis. Pearson correlation analysis and multivariate hierarchical regression were used to explore the influence of ICU nurses' occupational coping self-efficacy on presenteeism. Results: A total of 722 ICU nurses completed the questionnaire. The OCSE-N score of ICU nurses was (22.24 ± 6.15), and the SPS-6 score was (16.83 ± 4.24). The high presenteeism was 67.23%. Correlation analysis showed that in ICU nurses, OCSE-N total score was negatively correlated with SPS-6 total score (r = -0.421, p < 0.05), indicating that the higher the level of occupational coping self-efficacy, the lower the presenteeism. Multiple hierarchical regression analysis showed that occupational coping self-efficacy strongly predicted presenteeism, accounting for approximately 18.35% of the total variance. Conclusion: There is a correlation between ICU nurses' occupational coping self-efficacy and presenteeism, and nurses' occupational coping self-efficacy affects presenteeism differently. Managers should pay attention to nurses' occupational coping self-efficacy to promote nurses' presenteeism reduction.

17.
Plant Divers ; 46(1): 70-77, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38343594

ABSTRACT

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.

18.
J Nucl Med ; 65(3): 394-401, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38176714

ABSTRACT

Extensive research has been conducted on radiolabeled fibroblast activation protein (FAP) inhibitors (FAPIs) and p-Cl-Phe-cyclo(d-Cys-Tyr-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)d-Tyr-NH2 (LM3) peptides for imaging of FAP and somatostatin receptor 2 (SSTR2)-positive tumors. In this study, we designed and synthesized a FAPI-LM3 heterobivalent molecule radiolabeled with 68Ga and evaluated its effectiveness in both tumor xenografts and patients with nasopharyngeal carcinoma (NPC). Methods: The synthesis of FAPI-LM3 was based on the structures of FAPI-46 and LM3. After radiolabeling with 68Ga, its dual-receptor-binding affinity was evaluated in vitro and in vivo. Preclinical studies, including small-animal PET and biodistribution evaluation, were conducted on HT-1080-FAP and HT-1080-SSTR2 tumor xenografts. The feasibility of 68Ga-FAPI-LM3 PET/CT in a clinical setting was evaluated in patients with NPC, and the results were compared with those of 18F-FDG. Results: 68Ga-FAPI-LM3 showed high affinity for both FAP and SSTR2. The tumor uptake of 68Ga-FAPI-LM3 was significantly higher than that of 68Ga-FAPI-46 and 68Ga-DOTA-LM3 in HT-1080-FAP-plus-HT-1080-SSTR2 tumor xenografts. In a clinical study involving 6 NPC patients, 68Ga-FAPI-LM3 PET/CT showed significantly higher uptake than did 18F-FDG in primary and metastatic lesions, leading to enhanced lesion detectability and tumor delineation. Conclusion: 68Ga-FAPI-LM3 exhibited FAPI and SSTR2 dual-receptor-targeting properties both in vitro and in vivo, resulting in improved tumor uptake and retention compared with that observed with monomeric 68Ga-FAPI and 68Ga-DOTA-LM3. This study highlights the clinical feasibility of 68Ga-FAPI-LM3 PET/CT for NPC imaging.


Subject(s)
Nasopharyngeal Neoplasms , Positron Emission Tomography Computed Tomography , Animals , Humans , Gallium Radioisotopes , Fluorodeoxyglucose F18 , Nasopharyngeal Carcinoma/diagnostic imaging , Tissue Distribution , Positron-Emission Tomography , Nasopharyngeal Neoplasms/diagnostic imaging
19.
Sci Rep ; 14(1): 1564, 2024 01 18.
Article in English | MEDLINE | ID: mdl-38238592

ABSTRACT

The aim of this study was to determine the prognostic significance of anoikis related genes (ARGs) in ovarian cancer (OC) and to develop a prognostic signature based on ARG expression. We analyzed cohorts of OC patients and used nonnegative matrix factorization (NMF) for clustering. Single-sample gene-set enrichment analysis (ssGSEA) was employed to quantify immune infiltration. Survival analyses were performed using the Kaplan-Meier method, and differences in survival were determined using the log-rank test. The extent of anoikis modification was quantified using a risk score generated from ARG expression. The analysis of single-cell sequencing data was performed by the Tumor Immune Single Cell Hub (TISCH). Our analyses revealed two distinct patterns of anoikis modification. The risk score was used to evaluate the anoikis modification patterns in individual tumors. Three hub-genes were screened using the LASSO (Least Absolute Shrinkage and Selection Operator) method and patients were classified into different risk groups based on their individual score and the median score. The low-risk subtype was characterized by decreased expression of hub-genes and better overall survival. The risk score, along with patient age and gender, were considered to identify the prognostic signature, which was visualized using a nomogram. Our findings suggest that ARGs may play a novel role in the prognosis of OC. Based on ARG expression, we have developed a prognostic signature for OC that can aid in patient stratification and treatment decision-making. Further studies are needed to validate these results and to explore the underlying mechanisms.


Subject(s)
Anoikis , Ovarian Neoplasms , Humans , Female , Anoikis/genetics , Prognosis , Ovarian Neoplasms/genetics , Nomograms , Algorithms
20.
Curr Cancer Drug Targets ; 24(3): 319-327, 2024.
Article in English | MEDLINE | ID: mdl-37563818

ABSTRACT

AIMS: To investigate the short-term objective response and treatment toxicity of anlotinib as a combination treatment in patients with Recurrent or Metastatic Nasopharyngeal Carcinoma (RM-NPC). METHODS: Patients with RM-NPC who received anlotinib as a combination treatment between March 2021 and July 2022 were retrospectively analyzed.The efficacy and safety of anlotinib as a combination treatment were analyzed. RESULTS: A total of 17 patients with RM-NPC were included in this study. Of these patients, 2 (11.8%) had local recurrence, 4 (23.5%) had cervical lymph node recurrence, and 11 (64.9%) had distant failure. The most common metastatic site was the liver (47.1%), followed by the lung (23.5%) and bone (23.5%). Anlotinib was given as first-line treatment in 3 patients (17.6%), second lines treatment in 7 patients (41.2%), and third to six-lines treatment in 7 patients (41.2%). All patients received anlotinib combined with chemotherapy and/or immunotherapy. One patient achieved a complete response (5.9%), 7 patients had a partial response (41.2%), 5 patients had stable disease (29.4%), and 4 patients had progressive disease (23.5%). The overall disease control rate and the overall response rate were 76.5% and 47.1%, respectively. The median progression-free survival was 8.1 months, and the median overall survival was not reached. The incidence of grade 3 adverse events was 30%. No unexpected side effects or treatment-related death were observed. CONCLUSION: Anlotinib, as a combination treatment, has a promising antitumor activity and a manageable safety profile in patients with RM-NPC. Our results add to the growing evidence that supports the benefits of combining antiangiogenic drugs in RM-NPC. Randomized controlled clinical trials investigating the evaluation of anlotinib are warranted.


Subject(s)
Indoles , Nasopharyngeal Neoplasms , Neoplasm Recurrence, Local , Quinolines , Humans , Nasopharyngeal Carcinoma/drug therapy , Pilot Projects , Retrospective Studies , Neoplasm Recurrence, Local/drug therapy , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/pathology
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