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Recent advancements in cancer treatment have underscored the inadequacy of conventional monotherapies in addressing complex malignant tumors. Consequently, there is a growing interest in synergistic therapies capable of overcoming the limitations of monotherapies, leading to more personalized and effective approaches. Among these, the combination of photothermal therapy (PTT) and chemotherapy has emerged as a promising avenue for tumor management. In this study, we present a novel approach utilizing thermoresponsive mesoporous silica nanoparticles (MSN) as a delivery system for the chemotherapeutic drug doxorubicin. By incorporating photothermal agent copper sulfide (CuS) nanoparticles into the MSN, the resulting composite material exhibits potent photothermal properties. Furthermore, the integration of an upper critical solution temperature (UCST) polymer within the silica outer layer serves as a "gatekeeper", enabling precise control over drug release kinetics. This innovative nanomaterial effectively merges thermoresponsive behavior with PTT, thereby minimizing the collateral damage associated with traditional chemotherapy on healthy tissues. Moreover, in both in vitro studies using mouse breast carcinoma cells (4 T1) and in vivo experiments utilizing a 4 T1 tumor-bearing mouse model, our nanomaterials demonstrated synergistic effects, enhancing the anti-tumor efficacy of combined PTT and chemotherapy. With its remarkable photothermal conversion efficiency, robust stability, and biocompatibility, the UCST-responsive nanoplatform holds immense potential for clinical applications.
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BACKGROUND: Posterior cortical atrophy (PCA) is a rare condition characterized by early-onset and progressive visual impairment. Individuals with PCA have relatively early-onset and progressive dementia, posing certain needs for early detection. Hence, this study aimed to investigate the association of alterations in outer retinal and choroidal structure and microvasculature with PCA neuroimaging and clinical features and the possible effects of apolipoprotein E(APOE) ε4 allele on outer retinal and choroidal alterations in participants with PCA, to detect potential ocular biomarkers for PCA screening. METHODS: This cross-sectional study included PCA and age- and sex-matched healthy control participants from June 2022 to December 2023. All participants with PCA completed a comprehensive neurological evaluation. All participants were recorded baseline information and underwent an ophthalmic evaluation. Quantitative analyses were performed using swept-source optical coherence tomography (SS-OCT) and angiography (SS-OCTA). Adaptive optics scanning laser ophthalmoscopy (AO-SLO) was performed in some patients. In participants with PCA, the influence of APOE ε4 on outer retinal and choroidal alterations and the correlation of outer retinal and choroidal alterations with PCA neuroimaging and clinical features in participants with PCA were investigated. RESULTS: A total of 28 participants (53 eyes) with PCA and 56 healthy control participants (112 eyes) were included in the current study. Compared with healthy control participants, participants with PCA had significantly reduced outer retinal thickness (ORT) (p < 0.001), choriocapillaris vessel density (VD) (p = 0.007), choroidal vascular index (CVI) (p = 0.005) and choroidal vascular volume (CVV) (p = 0.003). In participants with PCA, APOE ε4 carriers showed thinner ORT (p = 0.009), and increased choriocapillaris VD (p = 0.004) and CVI (p = 0.004). The PCA neuroimaging features were positively associated with the ORT, CVI and CVV. Furthermore, differential correlations were observed of PCA clinical features with the CRT, CVV and CVI. CONCLUSIONS: Our findings highlighted the association of outer retinal and choroidal alterations with PCA neuroimaging and clinical features in participants with PCA. Noninvasive SS-OCT and SS-OCTA can provide potential biomarkers for the diagnosis and management of PCA, improving awareness of PCA syndrome among ophthalmologists, neurologists, and primary care providers.
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Choroid , Neuroimaging , Tomography, Optical Coherence , Humans , Male , Female , Cross-Sectional Studies , Middle Aged , Tomography, Optical Coherence/methods , Choroid/diagnostic imaging , Choroid/pathology , Aged , Neuroimaging/methods , Atrophy/pathology , Retina/diagnostic imaging , Retina/pathology , Apolipoprotein E4/geneticsABSTRACT
Background: Ethical behaviour in nursing practice is integral to establishing a harmonious nurse-patient relationship and improving the quality of care. A multitude of factors shapes such behaviour. Therefore, it is crucial to understand the interplay between these factors. Research objectives: This study aimed to explore the mechanisms underlying the influence of moral sensitivity on nurses' ethical behaviour and clarify the mediating role of moral courage. Research design: This cross-sectional quantitative study was conducted between July and August 2023. Participants and Research Context: The sample comprised 465 clinical nurses from three tertiary hospitals in Zhengzhou City, Henan Province, China. Data were collected using the Chinese version of the Moral Sensitivity Questionnaire-Revised Version, Nurses' Moral Courage Scale, and Ethical Behaviour Scale for Nurses. Data analysis was performed with SPSS 26.0 and AMOS 24.0, using descriptive statistics, Pearson correlation analysis, structural equation modelling, and bootstrapping methods. Ethical considerations: This study was approved by the Ethical Review Committee of Life Sciences of Zhengzhou University, China. Results: The participants were predominantly female (95.1%), with a mean age of 31.9 years. Moral courage and moral sensitivity were positively correlated with ethical behaviour. Moral sensitivity was positively associated with moral courage. Moral courage partially mediates the relationship between moral sensitivity and ethical behaviour. The indirect effect of nurses' moral sensitivity on ethical behaviour was quantified through moral courage (indirect effect = 0.290). Conclusion: Moral courage intermediates nurses' moral sensitivity and ethical behaviour. This conclusion provides nursing administrators with the insight that improving clinical nurses' moral sensitivity and courage can contribute to ensuring appropriate ethical behaviour.
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Objectives: This study aimed to construct prediction models based on computerized tomography (CT) signs, histogram and morphology features for the diagnosis of micropapillary or solid (MIP/SOL) components of stage IA lung adenocarcinoma (LUAC) and to evaluate the models' performance. Methods: This clinical retrospective study included image data of 376 patients with stage IA LUAC based on postoperative pathology, admitted to Putian First Hospital from January 2019 to June 2023. According to the presence of MIP/SOL components in postoperative pathology, patients were divided into MIP/SOL+ and MIP/SOL- groups. Cases with tumors ≤ 3 cm and ≤ 2 cm were separately analyzed. Each subgroup of patients was then randomly divided into a training set and a test set in a ratio of 7:3. The training set was used to build the prediction model, and the test set was used for internal validation. Results: For tumors ≤ 3 cm, ground-glass opacity (GGO) [odds ratio (OR) = 0.244; 95% confidence interval (CI): 0.103-0.569; p = 0.001], entropy (OR = 1.748; 95% CI: 1.213-2.577; p = 0.004), average CT value (OR = 1.002; 95% CI: 1.000-1.004; p = 0.002), and kurtosis (OR = 1.240; 95% CI: 1.023-1.513; p = 0.030) were independent predictors of MIP/SOL components of stage IA LUAC. The area under the ROC curve (AUC) of the nomogram prediction model for predicting MIP/SOL components was 0.816 (95% CI: 0.756-0.877) in the training set and 0.789 (95% CI: 0.689-0.889) in the test set. In contrast, for tumors ≤ 2 cm, kurtosis was no longer an independent predictor. The nomogram prediction model had an AUC of 0.811 (95% CI: 0.731-0.891) in the training set and 0.833 (95% CI: 0.733-0.932) in the test set. Conclusion: For tumors ≤ 3 cm and ≤ 2 cm, GGO, average CT value, and entropy were the same independent influencing factors in predicting MIP/SOL components of stage IA LUAC. The nomogram prediction models have potential diagnostic value for identifying MIP/SOL components of early-stage LUAC.
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Drought stress significantly affects the growth, development, and yield of cotton, triggering the response of multiple genes. Among them, ascorbate peroxidase (APX) is one of the important antioxidant enzymes in the metabolism of reactive oxygen species in plants, and APX enhances the ability of plants to resist oxidation, thus increasing plant stress tolerance. Therefore, enhancing the activity of APX in cells is crucial to improving plant stress resistance. Previous studies have isolated differentially expressed proteins under drought stress (GhAPX7) in drought-resistant (KK1543) and drought-sensitive (XLZ26) plants. Thus, this study analyzed the expression patterns of GhAPX7 in different cotton tissues to verify the drought resistance function of GhAPX7 and explore its regulatory pathways. GhAPX7 had the highest expression in cotton leaves, which significantly increased under drought stress, suggesting that GhAPX7 is essential for improving antioxidant capacity and enzyme activities in cotton. GhAPX7 silencing indirectly affects pronounced leaf yellowing and wilting in drought-resistant and drought-sensitive plants under drought stress. Malondialdehyde (MDA) content was significantly increased and chlorophyll and proline content and APX enzyme activity were generally decreased in silenced plants compared to the control. This result indicates that GhAPX7 may improve drought resistance by influencing the contents of MDA, chlorophyll, proline, and APX enzyme activity through increased expression levels. Transcriptome analysis revealed that the drought-related differentially expressed genes between the control and treated groups enriched plant hormone signal transduction, MAPK signaling, and plant-pathogen interaction pathways. Therefore, the decreased expression of GhAPX7 significantly affects the expression levels of genes in these three pathways, reducing drought resistance in plants. This study provides insights into the molecular mechanisms of GhAPX7 and its role in drought resistance and lays a foundation for further research on the molecular mechanisms of response to drought stress in cotton.
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Dysregulation of renal tubular epithelial cell (RTEC) apoptosis is one of the critical steps underlying the occurrence and development of nephrolithiasis. Although N6-methyladenosine (m6A) modification has been extensively studied and associated with various pathologic processes, research on its specific role in RTEC injury and apoptosis remains limited. In this study, we found that overexpression of ALKBH5 reduced the level of m6A modification in RTEC cells and notably promoted RTEC apoptosis. Further mechanism studies revealed that ALKBH5 mainly decreased the m6A level on the mRNA of Mucin 1 (MUC1) gene in RTECs. Moreover, ALKBH5 impaired the stability of MUC1 mRNA in RTECs, leading to attenuated expression of MUC1. Finally, we determined that the ALKBH5-MUC1 axis primarily facilitated RTEC apoptosis by regulating the PI3K/Akt signaling pathway. This study revealed the critical role of the ALKBH5-MUC1-PI3K/Akt regulatory system in RTEC apoptosis and provided new therapeutic targets for treating nephrolithiasis.
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There is insufficient data on systemic embolic events (SSEs) in patients with ischemic left ventricular aneurysm (LVA) concerning the impact of anticoagulation therapy. In this retrospective cohort study with 1043 patients with ischemic LVA, SSEs occurred in 7.2% over 2.4 years. After adjusting for relevant factors, the use of anticoagulants was independently associated with a lower incidence of SSE (3.1% vs. 9.0%, P < 0.001; subdistribution hazard ratios (SHR) 0.21, 95% confidence intervals (CI) 0.10-0.44, P < 0.001), with no significant difference in net adverse clinical events (NACEs) (10.6% vs. 13.3%, P = 0.225). Specifically, anticoagulation in patients with apical segment akinesis significantly reduced SSEs (3.9% vs. 13.6%, P = 0.002) and NACE rates (7.8% vs. 19.4%, P = 0.002). Major bleeding rates did not significantly differ between groups (5.6% vs. 3.5%, P = 0.111). These findings highlight the SSE risk in ischemic LVA and suggest potential benefits of anticoagulation, particularly in those with apical segment akinesis. These findings need to be validated in independent datasets.
Subject(s)
Anticoagulants , Heart Aneurysm , Humans , Retrospective Studies , Anticoagulants/therapeutic use , Male , Female , Aged , Middle Aged , Prognosis , Heart Aneurysm/drug therapy , Heart Aneurysm/epidemiology , Heart Ventricles/pathology , Heart Ventricles/drug effects , Heart Ventricles/physiopathology , Myocardial Ischemia/drug therapy , Myocardial Ischemia/epidemiology , Risk Factors , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Embolism/epidemiology , Embolism/drug therapyABSTRACT
Objectives: Newborns and small infants are unable to cooperate actively during diagnostic procedures; therefore, sedation is often employee to maintain immobilization and obtain high-quality images. However, these procedures are often indicated in sick, vulnerable, or hemodynamically unstable neonates and young infants, which raises the associated risks of sedation. This study summarizes our 4-year of experience with safe and effective procedural sedation in this vulnerable population. Study design: This retrospective study analyzed data on neonates and young infants who underwent non-painful diagnostic procedures from December 2019 to November 2023. Patients were categorized into the neonate (aged⦠28 days) and the young infant (29 days ⦠aged ⦠90 days) groups. Results: Non-pharmacological strategies, including sleeping naturally, swaddling/facilitated tucking, non-nutritive sucking, and skin-to-skin care, can achieve a success rate for sedation about 98.4%. In terms of pharmacological methods, our institution primarily utilizes chloral hydrate for procedural sedation in neonates and young infants undergoing non-painful diagnostic procedures. Midazolam serves as an alternative sedative. Chloral hydrate alone demonstrated a 92.5% success rate on the first attempt, compared to midazolam alone, with an 85.11% success rate. Neonates experienced a higher incidence of adverse events during sedation compared to young infants. Conclusion: This study reviews our 4-year experience with procedural sedation in neonates and young infants. Chloral hydrate demonstrated a high degree of safety and efficacy in this population. However, supervision by skilled medical personnel and extended observation is required. In our institution, the experience with midazolam is limited in this population, and further research is warranted to establish its safety and efficacy. Non-pharmacological strategies can achieve an acceptable rate of sedation success, which can be used based on patient's tolerance.
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BACKGROUND: There are conflicting reports on the factors that increase the likelihood of postpartum urinary retention (PUR). OBJECTIVES: We completed an updated systematic review and meta-analysis to identify the risk factors for PUR. SEARCH STRATEGY: An exhaustive search of the literature was undertaken using multiple databases, including PubMed, Web of Science, the Cochrane Library, and Embase to identify pertinent studies published up until November 4, 2023. SELECTION CRITERIA: Observational studies that provided outcomes to calculate the risk factors for PUR were included. DATA COLLECTION AND ANALYSIS: Two investigators separately performed the extraction of pertinent data from the articles. The risk factors for PUR were identified by pooling adjusted and unadjusted odds ratios (ORs) and 95% confidence intervals (CIs). Heterogeneity test, sensitivity analysis, and publication bias assessment were performed. MAIN RESULTS: This meta-analysis included 21 studies with a total of 36 951 participants. Meta-analysis was performed for 14 risk factors, and eight of these were statistically significant. The risk factors that were identified in this review included instrumental delivery (OR, 2.96 [95% CI, 1.82-4.80]; 95% prediction interval [PI], 0.67-12.98), relatively long duration of labor (OR, 1.04 [95% CI, 1.02-1.06]; 95% PI, 1.00-1.08), episiotomy (OR, 1.56 [95% CI, 1.19-2.06] 95% PI, 0.64-3.83), nulliparity (OR, 1.55 [95% CI, 1.30-1.84]; 95% PI, 0.94-2.77), epidural analgesia (OR, 2.99 [95% CI, 1.78-5.03]; 95% PI, 0.53-16.76), labor augmentation (OR, 2.21 [95% CI, 1.49-3.28]; 95% PI, 0.12-39.26), labor induction (OR, 1.73 [95% CI, 1.12-2.66]; 95% PI, 0.40-7.39), and perineal injury (OR, 2.75 [95% CI, 1.95-3.89]; 95% PI, 1.10-6.92). CONCLUSION: Instrumental delivery, extended labor duration, episiotomy, nulliparity, epidural analgesia, labor augmentation/induction, and perineal injury are significant risk factors for PUR. The findings could help physicians identify patients at risk in the postpartum setting.
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BACKGROUND: The relationship between amniotic fluid inflammatory biomarkers and preterm birth in second- or third-trimester pregnancy has been a focus, and understanding the correlation between these markers and preterm birth is important for early identification and intervention in preterm birth. The aim of this study was to explore potential inflammatory biomarkers in second- or third-trimester pregnancy amniotic fluid associated with preterm birth. METHODS: On November 30, 2023, we searched literature involved the influence of second- or third-trimester pregnancy amniotic fluid inflammatory biomarkers on preterm birth through PubMed, Web of Science, Embase, Scope, CNKI, WanFang, VIP and China Biomedical Databases. The search languages were Chinese and English. Included outcomes indexes were combined utility analysis via R software. RESULTS: A total of 11 articles were included in the combined utility analysis. This combined analysis revealed significant differences in several inflammatory biomarkers in amniotic fluid between the two groups (MD = 6.87, 95%CI: 0.26 - 13.47, P < 0.01); the difference in amniotic fluid IL-6 between the two groups (MD = 5.73, 95%CI: 3.13-8.32, P < 0.01); the difference in amniotic fluid IL-10 between the two groups (MD = 0.11, 95%CI: -3.26-3.48, P < 0.01); the difference in amniotic fluid CRP between the two groups (MD = 21.34, 95%CI: 11.69-30.89, P < 0.01); the difference in amniotic fluid MCP-1 between the two groups (MD = 312.14, 95%CI: 211.34-412.97, P < 0.01); the difference in the amniotic fluid MMP-9 between the two groups (MD = 0.86, 95%CI: -0.10-1.82, P < 0.01); and the difference in TNF-α in amniotic fluid between the two groups (MD = 22.78, 95%CI: -5.05-50.61, P < 0.01). CONCLUSIONS: The inflammatory biomarkers IL-1ß, IL-6, IL-10, CRP, TNFα, MCP-1 and MMP-9 in the amniotic fluid of patients in the second- or third-trimester pregnancy were all correlated with preterm birth.
The premature foetus has many serious complications in the near and long term because of the immature organs, which is related to the long-term incidence of cerebral palsy, developmental delay and retinopathy of prematurity, which is the main cause of perinatal foetal death. Preterm birth cases are accompanied by infection of pathogenic microorganisms in amniotic cavity, which then leads to inflammatory reaction in amniotic cavity. However, research on the correlation between inflammatory markers and preterm birth has shown certain complexity and differences. The results of this meta-analysis show that the inflammatory biomarkers interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and interleukin-10 (IL-10), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) in amniotic fluid of patients in the second- or third-trimester pregnancy are significant between the preterm birth group and the control group, and the expression level of inflammatory factors in amniotic fluid of patients in the preterm birth group is elevated, thus suggesting that these inflammatory factors may be able to predict preterm birth.
Subject(s)
Amniotic Fluid , Biomarkers , Premature Birth , Female , Humans , Pregnancy , Amniotic Fluid/chemistry , Amniotic Fluid/metabolism , Biomarkers/analysis , Biomarkers/metabolism , Inflammation/metabolism , Interleukin-10/analysis , Interleukin-10/metabolism , Interleukin-6/analysis , Interleukin-6/metabolism , Matrix Metalloproteinase 9/analysis , Matrix Metalloproteinase 9/metabolism , Pregnancy Trimester, Second , Pregnancy Trimester, Third , Premature Birth/metabolismABSTRACT
Porphyrin is a typical tetrapyrrole chromophore-based pigment with a special electronic structure and functionalities, which is frequently introduced into various porous organic polymers (POPs). Porphyrin-based POPs are widely used in various fields ranging from environmental and energy to biomedicine-related fields. Currently, most porphyrin-based POPs are prepared via the copolymerization of specific-group-functionalized porphyrins with other building blocks, in which the tedious and inefficient synthesis procedure for the porphyrin greatly hinders the development of such materials. This review aimed to summarize information on porphyrin-based POPs synthesized using the Alder-Longo method, thereby skipping the complex synthesis of porphyrin-bearing monomers, in which the porphyrin macrocycles are formed directly via the cyclic tetramerization of pyrrole with monomers containing multiple aldehyde groups during the polymerization process. The representative applications of porphyrin-based POPs derived using the Alder-Longo method are finally introduced, which pinpoints a clear relationship between the structure and function from the aspect of the building blocks used and porous structures. This review is therefore valuable for the rational design of efficient porphyrin-based porous organic polymer systems that may be utilized in various fields from energy-related conversion/storage technologies to biomedical science.
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Bluetongue disease is an infectious disease transmitted by Culicoides as vectors, mainly infecting ruminants. Because ruminants play an important role in animal husbandry in China, the outbreak of bluetongue disease can cause serious economic losses. Maxent model was applied to predict the distribution of bluetongue in China based on the data derived from domestic and foreign academic literature databases including CNKI, Wanfang Database, PubMed, Web of Science and Google Scholar. The results showed that annual mean temperature (BIO1), precipitation in driest month (BIO14), sheep density (SD) and altitude (Elev) were the relevant variables of bioclimatic suitable zones for bluetongue disease. Precipitation in wettest month (BIO13), BIO1, BIO14, Elev were the main variables affecting the habitat of the bluetongue vector Culicoides. The most suitable climate for bluetongue infection occurs in southern China, central China and parts of Xinjiang. The suitable living areas of Culicoides are mainly located in southern, central and eastern China, and the overlap of the two suitable areas is high. The study suggested that southern, central, and eastern China are high-risk areas for bluetongue due to the significant overlap of suitable habitats for both the disease and its vector. Implementing effective surveillance and targeted control strategies in these regions is crucial for mitigating the impact of bluetongue disease.
Subject(s)
Bluetongue , Ceratopogonidae , Bluetongue/transmission , Bluetongue/epidemiology , Animals , China/epidemiology , Ceratopogonidae/virology , Sheep , Insect Vectors/virology , Bluetongue virus/physiology , ClimateABSTRACT
In this study, electroporation-surface-enhanced Raman scattering (SERS) was applied to rapidly measure intracellular pH. The generation of a sensitive SERS probe for measuring pH in the range of 6.0-8.0 was accomplished through the conjugation of the pH-sensitive molecule 4-mercaptobenzoic acid (4-MBA) to the surface of gold nanoparticles (Au NPs) through its thiol functional group. This bioprobe was then rapidly introduced into nasopharyngeal carcinoma CNE-1 cells by electroporation, followed by SERS scanning and the fitting of intensity ratios of each detection point's Raman peaks at 1423 cm-1 and 1072 cm-1, to create the pH distribution map of CNE-1 cells. The electroporation-SERS assay introduces pH bioprobes into a living cell in a very short time and disperses the nanoprobe throughout the cytoplasm, ultimately enabling rapid and comprehensive pH analysis of the entire cell. Our work demonstrates the potential of electroporation-SERS for the biochemical analysis of live cells.
Subject(s)
Electroporation , Gold , Metal Nanoparticles , Spectrum Analysis, Raman , Spectrum Analysis, Raman/methods , Hydrogen-Ion Concentration , Electroporation/methods , Humans , Gold/chemistry , Metal Nanoparticles/chemistry , Cell Line, Tumor , Sulfhydryl Compounds/chemistry , Sulfhydryl Compounds/analysis , Benzoates/chemistryABSTRACT
Large amounts of wastewater containing low-concentration (<10 ppm) rare-earth ions (REIs) are discharged annually in China's rare-earth mining and processing industry, resulting in severe environmental pollution and economic losses. Hence, achieving efficient selective recovery of low-concentration REIs from REIs-containing wastewater is essential for environmental protection and resource recovery. In this study, a pseudocapacitance system was designed for highly efficient capacitive selective recovery of REIs from wastewater using the titanium dioxide/P/C (TiO2/P/C) composite electrode, which exhibited over 99% recovery efficiency for REIs, such as Eu3+, Dy3+, Tb3+, and Lu3+ in mixed solution. This system maintained high efficiency and more than 90 times the enrichment concentration of REIs even after 100 cycles. Ti4+ of TiO2 was reduced to Ti3+ of Ti3O5 under forward voltage in the system, which trapped the electrons of phosphorus site and caused it to be oxidized to phosphate with a strong affinity for REIs, thus improving the selectivity of REIs. Under reverse voltage, Ti3O5 was oxidized to TiO2, which transferred electrons to phosphate and transformed to the phosphorus site, resulting in the desorption and enrichment of REIs and the regeneration of the electrode. This study provides a promising method for the efficient recovery of REIs from wastewater.
Subject(s)
Electrodes , Metals, Rare Earth , Phosphorus , Titanium , Wastewater , Wastewater/chemistry , Metals, Rare Earth/chemistry , Phosphorus/chemistry , Adsorption , Titanium/chemistry , Water Pollutants, Chemical/chemistry , IonsABSTRACT
Elevated infiltration of tumor-associated macrophages (TAMs) drives tumor progression and correlates with poor prognosis for various tumor types. Our research identifies that the ablation of the Pim-1 proto-oncogene (PIM1) in non-small cell lung cancer (NSCLC) suppresses TAM infiltration and prevents them from polarizing toward the M2 phenotype, thereby reshaping the tumor immune microenvironment (TME). The predominant mechanism through which PIM1 exerts its impact on macrophage chemotaxis and polarization involves CC motif chemokine ligand 2 (CCL2). The expression level of PIM1 is positively correlated with high CCL2 expression in NSCLC, conferring a worse overall patient survival. Mechanistically, PIM1 deficiency facilitates the reprogramming of TAMs by targeting nuclear factor kappa beta (NF-κB) signaling and inhibits CCL2 transactivation by NSCLC cells. The decreased secretion of CCL2 impedes TAM accumulation and their polarization toward a pro-tumoral phenotype. Furthermore, Dual blockade of Pim1 and PD-1 collaboratively suppressed tumor growth, repolarized macrophages, and boosted the efficacy of anti-PD-1 antibody. Collectively, our findings elucidate the pivotal role of PIM1 in orchestrating TAMs within the TME of NSCLC and highlight the potential of PIM1 inhibition as a strategy for enhancing the efficacy of cancer immunotherapy.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Chemokine CCL2 , Lung Neoplasms , NF-kappa B , Proto-Oncogene Proteins c-pim-1 , Tumor Microenvironment , Tumor-Associated Macrophages , Proto-Oncogene Proteins c-pim-1/antagonists & inhibitors , Proto-Oncogene Proteins c-pim-1/metabolism , Proto-Oncogene Proteins c-pim-1/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/genetics , Tumor Microenvironment/immunology , Humans , Chemokine CCL2/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/immunology , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Lung Neoplasms/genetics , Mice , NF-kappa B/metabolism , Animals , Tumor-Associated Macrophages/immunology , Tumor-Associated Macrophages/metabolism , Proto-Oncogene Mas , Macrophages/immunology , Macrophages/metabolism , Cell Line, Tumor , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Signal Transduction , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/metabolismABSTRACT
BACKGROUND: Williams-Beuren syndrome, Noonan syndrome, and Alagille syndrome are common types of genetic syndromes (GSs) characterized by distinct facial features, pulmonary stenosis, and delayed growth. In clinical practice, differentiating these three GSs remains a challenge. Facial gestalts serve as a diagnostic tool for recognizing Williams-Beuren syndrome, Noonan syndrome, and Alagille syndrome. Pretrained foundation models (PFMs) can be considered the foundation for small-scale tasks. By pretraining with a foundation model, we propose facial recognition models for identifying these syndromes. METHODS: A total of 3297 (n = 1666) facial photos were obtained from children diagnosed with Williams-Beuren syndrome (n = 174), Noonan syndrome (n = 235), and Alagille syndrome (n = 51), and from children without GSs (n = 1206). The photos were randomly divided into five subsets, with each syndrome and non-GS equally and randomly distributed in each subset. The proportion of the training set and the test set was 4:1. The ResNet-100 architecture was employed as the backbone model. By pretraining with a foundation model, we constructed two face recognition models: one utilizing the ArcFace loss function, and the other employing the CosFace loss function. Additionally, we developed two models using the same architecture and loss function but without pretraining. The accuracy, precision, recall, and F1 score of each model were evaluated. Finally, we compared the performance of the facial recognition models to that of five pediatricians. RESULTS: Among the four models, ResNet-100 with a PFM and CosFace loss function achieved the best accuracy (84.8%). Of the same loss function, the performance of the PFMs significantly improved (from 78.5% to 84.5% for the ArcFace loss function, and from 79.8% to 84.8% for the CosFace loss function). With and without the PFM, the performance of the CosFace loss function models was similar to that of the ArcFace loss function models (79.8% vs 78.5% without PFM; 84.8% vs 84.5% with PFM). Among the five pediatricians, the highest accuracy (0.700) was achieved by the senior-most pediatrician with genetics training. The accuracy and F1 scores of the pediatricians were generally lower than those of the models. CONCLUSIONS: A facial recognition-based model has the potential to improve the identification of three common GSs with pulmonary stenosis. PFMs might be valuable for building screening models for facial recognition. Key messages What is already known on this topic: Early identification of genetic syndromes (GSs) is crucial for the management and prognosis of children with pulmonary stenosis (PS). Facial phenotyping with convolutional neural networks (CNNs) often requires large-scale training data, limiting its usefulness for GSs. What this study adds: We successfully built multi-classification models based on face recognition using a CNN to accurately identify three common PS-associated GSs. ResNet-100 with a pretrained foundation model (PFM) and CosFace loss function achieved the best accuracy (84.8%). Pretrained with the foundation model, the performance of the models significantly improved, although the impact of the type of loss function appeared to be minimal. How this study might affect research, practice, or policy: A facial recognition-based model has the potential to improve the identification of GSs in children with PS. The PFM might be valuable for building identification models for facial detection.
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Background: The benefits of home enteral nutrition (HEN) are increasingly recognized, with more scholars focusing on this field. This study aimed to comprehensively identify collaborative networks, analyze, and track research trends, focus on current hotspots, and accurately predict the forefront and focus of home enteral nutrition. Methods: A computer search of the Web of Science Core Collection (WoSCC) was conducted for studies related to home enteral nutrition published from January 1, 2004, to December 31, 2023, and select them in compliance with the PRISMA guidelines. The CiteSpace software was used for bibliometric visualization and comparative analysis of countries, institutions, journals, references, and keywords. Results: A total of 1,113 documents were included, showing a steady annual increase in publication volume. The United States and the Mayo Clinic were the top publishing country and institution, with 302 and 41 papers, respectively. "CLIN NUTR" had the highest number of publications, totaling 221, while "ESPEN guideline on home enteral nutrition" was the most cited reference, with 43 citations. The most prolific author was Manpreet S with 29 papers. Conclusion: The management of HEN is a current research hotspot. The safety of HEN and how to improve patient compliance are critical areas for researchers to consider. Future research could focus on these aspects. The blurring of boundaries between hospital and home care and how to utilize telemedicine technologies to serve more patients deserve in-depth exploration. Researchers worldwide should combine their unique characteristics and advantages to strengthen international cooperation.
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Introduction: This study investigates the role of hypoxia-related genes in the neuroprotective efficacy of Yang Xue oral liquid (YXKFY) in Alzheimer's disease (AD) and Parkinson's disease (PD). Methods and results: Using differential expression and weighted gene co-expression network analysis (WGCNA), we identified 106 and 9 hypoxia-associated genes in AD and PD, respectively, that are implicated in the transcriptomic and proteomic profiles. An artificial intelligence-driven hypoxia signature (AIDHS), comprising 17 and 3 genes for AD and PD, was developed and validated across nine independent cohorts (n = 1713), integrating 10 machine learning algorithms and 113 algorithmic combinations. Significant associations were observed between AIDHS markers and immune cells in AD and PD, including naive CD4+ T cells, macrophages, and neutrophils. Interactions with miRNAs (hsa-miR-1, hsa-miR-124) and transcription factors (USF1) were also identified. Single-cell RNA sequencing (scRNA-seq) data highlighted distinct expression patterns of AIDHS genes in various cell types, such as high expression of TGM2 in endothelial cells, PDGFRB in endothelial and mesenchymal cells, and SYK in microglia. YXKFY treatment was shown to repair cellular damage and decrease reactive oxygen species (ROS) levels. Notably, genes with previously dysfunctional expression, including FKBPL, TGM2, PPIL1, BLVRB, and PDGFRB, exhibited significant recovery after YXKFY treatment, associated with riboflavin and lysicamine. Conclusion: The above genes are suggested to be central to hypoxia and neuroinflammation responses in AD and PD, and are potential key mediators of YXKFY's neuroprotective action.
ABSTRACT
Objective: To determine the efficacy of mechanical thrombectomy combined with prolonged mild hypothermia compared with conventional treatment in managing acute middle cerebral artery occlusion, and to explore whether extending the duration of hypothermia can improve neurological function. Method: From 2018 to June 2023, a retrospective analysis was conducted on 45 patients with acute middle cerebral artery occlusion treated at the NICU of Suzhou Kowloon Hospital, affiliated with Shanghai Jiao Tong University School of Medicine. After thrombectomy, patients were admitted to the neurological intensive care unit (NICU) for targeted temperature management. Patients were divided into two groups: the mild hypothermia group (34.5-35.9°C) receiving 5-7 days of treatment, and the normothermia group (control group) whose body temperature was kept between 36 and 37.5°C using pharmacological and physical cooling methods. Baseline characteristics and temperature changes were compared between the two groups of patients. The primary outcome was the modified Rankin Scale (mRS) score at 3 month after surgery, and the secondary outcomes were related complications and mortality rate. Prognostic risk factors were investigated using both univariate and multivariate logistic regression analyses. Results: Among 45 patients, 21 underwent prolonged mild hypothermia, and 24 received normothermia, with no significant differences in baseline characteristics between the two groups. The duration of mild hypothermia ranged from 5 to 7 days. The incidence of chills (33.3% vs. 8.3%, p = 0.031) and constipation (57.1% vs. 20.8%, p = 0.028) was significantly higher in the mild hypothermia group compared with the control group. There was no significant difference in mortality rates between the mild hypothermia and the control group (4.76% vs. 8.33%, p = 1.000, OR = 1.75, 95% CI, 0.171-17.949). At 3 month, there was no significant difference in the modified mRS (0-3) score between the mild hypothermia and control groups (52.4% vs. 25%, p = 0.114, OR = 0.477, 95% CI, 0.214-1.066). Infarct core volume was an independent risk factor for adverse neurological outcomes. Conclusion: Prolonged mild hypothermia following mechanical thrombectomy had no severe complications and shows a trend to improve the prognosis of neurological function. The Infarct core volume on CTP was an independent risk factor for predicting neurological function.