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1.
Medicine (Baltimore) ; 103(23): e38416, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847724

ABSTRACT

To investigate the expression of Inhibin B between various clinical stages, Chinese medicine dialectic typing, and in nasopharyngeal carcinoma (NPC) tissues and serum, and to evaluate the potential of Inhibin B as a new biomarker for NPC. Paraffin specimens of pathologically confirmed NPC tissues and paracancerous tissues were retrospectively collected, and the expression of Inhibin α (INHA) and Inhibin ßB (INHBB) was detected by SP method, and their relationship with clinicopathological indexes was analyzed; in addition, patients with NPC who had received radiotherapy were included as the study subjects, and Epstein-Barr virus DNA (EBV-DNA), INHA, and INHBB in patients were detected by using the fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and chemiluminescent immuno-sandwiching method, respectively. EBV-DNA, EBV-viral capsid antigen-immunoglobulin A (VCA IgA), INHA, and INHBB were detected in the patients, respectively, and their relationships with traditional Chinese medicine (TCM) patterns were also analyzed. The expression of INHA and INHBB in NPC tissues was lower than that in paracancerous tissues, and the expression of INHA in NPC patients was correlated with lymphatic metastasis, clinical staging, and TCM staging; the levels of EBV-DNA and VCA IgA were higher than that of healthy populations in NPC patients and were higher than that of patients with stage III + IV than that of patients with stage I + II, and the levels of INHA and INHBB were lower than those of healthy populations and were lower than those of patients with stage III + IV than that of patients with stage I + II. The levels of INHA and INHBB in nasopharyngeal cancer patients were lower than those in healthy people, and the levels in stage III + IV patients were lower than those in stage I + II patients. The levels of EBV-DNA and VCA IgA in nasopharyngeal cancer patients were correlated with the Chinese medicine patterns, and had different patterns. The expression of Inhibin B may be related to the progression of NPC, and it has certain typing significance for different TCM syndromes of NPC, which is helpful for TCM typing diagnosis.


Subject(s)
Medicine, Chinese Traditional , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , Male , Female , Nasopharyngeal Neoplasms/virology , Nasopharyngeal Neoplasms/diagnosis , Nasopharyngeal Neoplasms/blood , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Carcinoma/diagnosis , Nasopharyngeal Carcinoma/virology , Nasopharyngeal Carcinoma/blood , Nasopharyngeal Carcinoma/metabolism , Nasopharyngeal Carcinoma/pathology , Medicine, Chinese Traditional/methods , Middle Aged , Retrospective Studies , Adult , DNA, Viral/analysis , DNA, Viral/blood , Inhibins/blood , Herpesvirus 4, Human/genetics , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/blood , Neoplasm Staging , Inhibin-beta Subunits/metabolism , Inhibin-beta Subunits/blood , Aged , Antigens, Viral/blood , Immunoglobulin A/blood , Capsid Proteins
2.
Front Pharmacol ; 15: 1407335, 2024.
Article in English | MEDLINE | ID: mdl-38846099

ABSTRACT

Ferroptosis is a non-apoptotic mode of programmed cell death characterized by iron dependence and lipid peroxidation. Since the ferroptosis was proposed, researchers have revealed the mechanisms of its formation and continue to explore effective inhibitors of ferroptosis in disease. Recent studies have shown a correlation between ferroptosis and the pathological mechanisms of neurodegenerative diseases, as well as diseases involving tissue or organ damage. Acting on ferroptosis-related targets may provide new strategies for the treatment of ferroptosis-mediated diseases. This article specifically describes the metabolic pathways of ferroptosis and summarizes the reported mechanisms of action of natural and synthetic small molecule inhibitors of ferroptosis and their efficacy in disease. The paper also describes ferroptosis treatments such as gene therapy, cell therapy, and nanotechnology, and summarises the challenges encountered in the clinical translation of ferroptosis inhibitors. Finally, the relationship between ferroptosis and other modes of cell death is discussed, hopefully paving the way for future drug design and discovery.

3.
Front Psychiatry ; 15: 1342376, 2024.
Article in English | MEDLINE | ID: mdl-38827438

ABSTRACT

Background: The causative relationship between chronic rhinosinusitis (CRS) and depression remains unclear. Herein we employed Mendelian randomization (MR) coupled with single-cell analysis to investigate the causality between CRS and depression. Methods: Data pertaining to CRS and depression were mined from the genome-wide association study database, and a single-cell dataset was sourced from the literature. To explore causality, we conducted bidirectional MR analysis using MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode, with IVW representing the most important method. Further, sensitivity analysis was performed to evaluate the robustness of MR analysis results. Candidate genes were analyzed via single-cell combined MR analysis. Results: Forward MR analysis indicated depression as a risk factor for CRS when depression was the exposure factor and CRS was the outcome (OR = 1.425, P < 0.001). Reverse MR analysis revealed the same positive relationship between CRS and depression when CRS was the exposure factor and depression was the outcome (OR = 1.012, P = 0.038). Sensitivity analysis validated the robustness of bidirectional MR analysis results. Ten cell types (endothelial, ciliated, basal, myeloid, mast, apical, plasma, glandular, fibroblast, and T cells) were identified in the single-cell dataset. The network of receptor-ligand pairs showed that in normal samples, cell-cell interactions were present among various cell types, such as epithelial, mast, myeloid, and endothelial cells. In contrast, CRS samples featured only one specific receptor-ligand pair, confined to myeloid cells. TCF4 and MEF2C emerged as potentially crucial for CRS-associated depression development. Conclusions: Our findings suggest a bidirectional causal relationship between CRS and depression, offering a new perspective on the association between CRS and depression.

4.
Mol Neurobiol ; 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38878116

ABSTRACT

The amyloid-beta (Aß) aggregation in Alzheimer's disease (AD) triggers neuroinflammation, and neurodegeneration, which lead to cognitive deficits along with other neuropsychiatric symptoms, including depression and anxiety. G protein-coupled receptor 35 (GPR35) is expressed in the brain and is involved in metabolic stresses. However, the role of GPR35 in AD pathogenesis remains unknown. Herein, pharmacological blockade, shRNA-mediated knockdown or knockout of GPR35 was performed to investigate the role and mechanisms of GPR35 in Aß1-42-induced cognitive impairment and emotional alterations in mice. A series of behavioral, histopathological, and biochemical tests were performed in mice. Our results showed that hippocampal GPR35 expression was significantly increased in Aß1-42-induced and APP/PS1 AD mouse models. Pharmacological blockade or knockdown of GPR35 ameliorated cognitive impairment and emotional alterations induced by Aß1-42 in mice. We also found that blockade or knockdown of GPR35 decreased the accumulation of Aß, and improved neuroinflammation, cholinergic system deficiency, and neuronal apoptosis via the RhoA/ROCK2 pathway in Aß1-42-treaed mice. However, activation of GPR35 aggravates Aß1-42-induced cognitive deficits and emotional alterations in mice. In addition, genetic deletion of GPR35 protects against the Aß1-42-induced cognitive deficits and emotional alterations in mice. Moreover, GPR35 could bind to TLR4. These results indicate that GPR35 participates in the pathogenesis of cognitive deficits and emotional alterations induced by Aß1-42 in mice, suggesting that GPR35 could be a potential therapeutic target for AD.

6.
J Environ Manage ; 364: 121448, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38870797

ABSTRACT

Submerged zone in bioretention facilities for stormwater treatment has been approved to be an effective structure amendment to improve denitrification capability. However, the role and influence of water quality changes in the submerged zone under natural continuous random rainfall patterns are still not clear, especially when the rainfall is less than the pore water in the submerged zone. In this study, continuous rainfall events with different rainfall volume (light rain-light rain-heavy rain) were designed in a lab-scale woodchip mulched pyrite bioretention facility to test the effects of rainfall pattern. The results exhibited that light rain events significantly affected the pollutant removal performance of bioretention for the next rainfall. Different effects were observed during the long-term operation. In the 5th month, light rain reduced the ammonia removal efficiency of subsequent rainstorm events by 8.70%, while in the 12th month, when nitrate leakage occurred, light rain led to a 40.24% reduction in the next heavy rain event's nitrate removal efficiency. Additionally, light rain would also affect the concentration of by-products in the next rainfall. Following a light rain, the concentration of sulfate in the subsequent light rainfall can increase by 24.4 mg/L, and by 11.92 mg/L in a heavy rain. The water quality in the submerged zone and media characteristics analysis suggested that nitrogen conversion capacity of the substrate and microbes, such as Nitrospira (2.86%) and Thiobacillus (35.71%), as well as the in-situ accumulation of pollutants under light rain played important roles. This study clarifies the relationship between successive rainfall events and provides a more comprehensive understanding of bioretention facilities. This is beneficial for field study of bioretention facilities in the face of complex rainfall events.

8.
Sci Total Environ ; : 173947, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38880148

ABSTRACT

Mine fires caused by spontaneous coal combustion are major disasters in coal mines. The staged oxidation kinetic parameters of various coal samples at oxygen concentrations of 21 %, 15 %, 10 %, 5 %, and 3 % were analyzed using a programmed temperature testing system. Herein, the temperature increase rate of coal, the temperature difference between the furnace and coal, and the oxygen consumption characteristics were obtained. Based on the amount of CO produced and the temperature sensitivity coefficient, three characteristic temperatures and four stages of low-temperature oxidation (LTO) were identified. The results showed that at a critical temperature (TC), the amount of CO gas released from the coal samples increased with increasing oxygen concentration, and the difference in the oxygen consumption rate increased. After the limit temperature (Tu), the amount of CO gas increased steadily, and the increase in the oxygen consumption rate stagnated. CO production, the maximum heating rate, and the maximum heat release rate were positively correlated with the oxygen concentration. As the oxygen concentration increased, the activation energy during the oxygen absorption stage gradually decreased. The average reaction enthalpy (ΔH) of pre-oxidized water-immersed coal was 19.37 kJ/kg greater than that of raw coal. The equation for the conservation of energy of the coal oxidation warming process was normalized. The theoretical values of the awakening stage and the stable stage were τν and τν (1-B), respectively. When B was >1, pre-oxidized water-immersed coal at a low oxygen concentration was prone to crossover points during the oxygen absorption stage, which increased the risk of coal spontaneous combustion (CSC). The research results could provide a theoretical basis for the staged control of the spontaneous combustion of water-immersed coal in goaf areas.

9.
Environ Sci Technol ; 58(24): 10776-10785, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38838101

ABSTRACT

Rivers have been recognized as the primary conveyors of microplastics to the oceans, and seaward transport flux of riverine microplastics is an issue of global attention. However, there is a significant discrepancy in how microplastic concentration is expressed in field occurrence investigations (number concentration) and in mass flux (mass concentration). Of urgent need is to establish efficient conversion models to correlate these two important paradigms. Here, we first established an abundant environmental microplastic dataset and then employed a deep neural residual network (ResNet50) to successfully separate microplastics into fiber, fragment, and pellet shapes with 92.67% accuracy. We also used the circularity (C) parameter to represent the surface shape alteration of pellet-shaped microplastics, which always have a more uneven surface than other shapes. Furthermore, we added thickness information to two-dimensional images, which has been ignored by most prior research because labor-intensive processes were required. Eventually, a set of accurate models for microplastic mass conversion was developed, with absolute estimation errors of 7.1, 3.1, 0.2, and 0.9% for pellet (0.50 ≤ C < 0.75), pellet (0.75 ≤ C ≤ 1.00), fiber, and fragment microplastics, respectively; environmental samples have validated that this set is significantly faster (saves ∼2 h/100 MPs) and less biased (7-fold lower estimation errors) compared to previous empirical models.


Subject(s)
Environmental Monitoring , Microplastics , Water Pollutants, Chemical , Rivers/chemistry
10.
Langmuir ; 40(24): 12818-12827, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38842118

ABSTRACT

The rebound dynamics of double droplets impacting an inclined superhydrophobic surface decorated with macro-ridges are investigated via lattice Boltzmann method (LBM) simulations. Four rebound regions are identified, that is, the no-coalescence-rebound (NCR), the partial-coalescence-rebound of the middle part bounces first (PCR-M), and the side part bounces first (PCR-S), as well as the complete-coalescence-rebound (CCR). The occurrence of the rebound regions strongly depends on the droplet arrangement, the center-to-center distance of the droplets, and the Weber number. Furthermore, the contact time is closely related to the rebound regions. The PCR-M region can significantly reduce the contact time because the energy dissipation in this region may decrease which can promote the rebound dynamic. Intriguingly, the contact time is also affected by the droplet arrangement; i.e., droplets arranged parallel to the ridge dramatically shorten the contact time since this arrangement increases the asymmetry of the liquid film. Therefore, for multidrop impact, the contact time can be effectively manipulated by changing the rebound region and the droplet arrangement. This work focuses on elucidating the wetting behaviors, rebound regions, and contact time of the multiple-droplet impacting an inclined superhydrophobic surface decorated with macro-ridges.

11.
Geriatr Nurs ; 58: 344-351, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38875761

ABSTRACT

PURPOSE: This study aimed to understand how age, health status, and lifestyle impact bone mineral density (BMD) in middle-aged and older adults, focusing on predicting osteoporosis risk. METHODS: This study included 2836 participants aged 50-88 from the Health Improvement Program of Bone (HOPE) conducted from 2021 to 2023. We used logistic regression to make a prediction tool. Then checked its accuracy and reliability using receiver operating characteristic (ROC) and calibration curves. RESULTS: Factors like age, body weight, prior fractures, and smoking were independently found to affect BMD T-score distribution in men. In women, age and body weight were identified as independent factors influencing BMD T-score distribution. A nomogram was created to visually illustrate these predictive relationships. CONCLUSIONS: The nomogram proved highly accurate in identifying men aged 50 and above and postmenopausal women based on their BMD T-score distribution, improving clinical decision-making and patient care in osteoporosis evaluation and treatment.

12.
Cell Rep ; 43(6): 114356, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38865246

ABSTRACT

In addition to its role in vision, light also serves non-image-forming visual functions. Despite clinical evidence suggesting the antipruritic effects of bright light treatment, the circuit mechanisms underlying the effects of light on itch-related behaviors remain poorly understood. In this study, we demonstrate that bright light treatment reduces itch-related behaviors in mice through a visual circuit related to the lateral parabrachial nucleus (LPBN). Specifically, a subset of retinal ganglion cells (RGCs) innervates GABAergic neurons in the ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL), which subsequently inhibit CaMKIIα+ neurons in the LPBN. Activation of both the vLGN/IGL-projecting RGCs and the vLGN/IGL-to-LPBN projections is sufficient to reduce itch-related behaviors induced by various pruritogens. Importantly, we demonstrate that the antipruritic effects of bright light treatment rely on the activation of the retina-vLGN/IGL-LPBN pathway. Collectively, our findings elucidate a visual circuit related to the LPBN that underlies the antipruritic effects of bright light treatment.

13.
Neurochem Res ; 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38864944

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease with a challenging treatment landscape, due to its complex pathogenesis and limited availability of clinical drugs. Ferroptosis, an iron-dependent form of programmed cell death (PCD), stands distinct from apoptosis, necrosis, autophagy, and other cell death mechanisms. Recent studies have increasingly highlighted the role of iron deposition, reactive oxygen species (ROS) accumulation, oxidative stress, as well as systemic Xc- and glutamate accumulation in the antioxidant system in the pathogenesis of amyotrophic lateral sclerosis. Therefore, targeting ferroptosis emerges as a promising strategy for amyotrophic lateral sclerosis treatment. This review introduces the regulatory mechanism of ferroptosis, the relationship between amyotrophic lateral sclerosis and ferroptosis, and the drugs used in the clinic, then discusses the current status of amyotrophic lateral sclerosis treatment, hoping to provide new directions and targets for its treatment.

14.
Sci Rep ; 14(1): 12766, 2024 06 04.
Article in English | MEDLINE | ID: mdl-38834715

ABSTRACT

Metabolic reprogramming is widely recognized as a hallmark of malignant tumors, and the targeting of metabolism has emerged as an appealing approach for cancer treatment. Mitochondria, as pivotal organelles, play a crucial role in the metabolic regulation of tumor cells, and their morphological and functional alterations are intricately linked to the biological characteristics of tumors. As a key regulatory subunit of mitochondria, mitochondrial inner membrane protein (IMMT), plays a vital role in degenerative diseases, but its role in tumor is almost unknown. The objective of this research was to investigate the roles that IMMT play in the development and progression of breast cancer (BC), as well as to elucidate the underlying biological mechanisms that drive these effects. In this study, it was confirmed that the expression of IMMT in BC tissues was significantly higher than that in normal tissues. The analysis of The Cancer Genome Atlas (TCGA) database revealed that IMMT can serve as an independent prognostic factor for BC patients. Additionally, verification in clinical specimens of BC demonstrated a positive association between high IMMT expression and larger tumor size (> 2 cm), Ki-67 expression (> 15%), and HER-2 status. Furthermore, in vitro experiments have substantiated that the suppression of IMMT expression resulted in a reduction in cell proliferation and alterations in mitochondrial cristae, concomitant with the liberation of cytochrome c, but it did not elicit mitochondrial apoptosis. Through Gene Set Enrichment Analysis (GSEA) analysis, we have predicted the associated metabolic genes and discovered that IMMT potentially modulates the advancement of BC through its interaction with 16 metabolic-related genes, and the changes in glycolysis related pathways have been validated in BC cell lines after IMMT inhibition. Consequently, this investigation furnishes compelling evidence supporting the classification of IMMT as prognostic marker in BC, and underscoring its prospective utility as a novel target for metabolic therapy.


Subject(s)
Breast Neoplasms , Cell Proliferation , Mitochondria , Mitochondrial Proteins , Humans , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/genetics , Female , Mitochondria/metabolism , Mitochondrial Proteins/metabolism , Mitochondrial Proteins/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Middle Aged , Prognosis , Membrane Proteins/metabolism , Membrane Proteins/genetics , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , MCF-7 Cells , Muscle Proteins
15.
IEEE Trans Med Imaging ; PP2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38861436

ABSTRACT

Medical image reporting focused on automatically generating the diagnostic reports from medical images has garnered growing research attention. In this task, learning cross-modal alignment between images and reports is crucial. However, the exposure bias problem in autoregressive text generation poses a notable challenge, as the model is optimized by a word-level loss function using the teacher-forcing strategy. To this end, we propose a novel Token-Mixer framework that learns to bind image and text in one embedding space for medical image reporting. Concretely, Token-Mixer enhances the cross-modal alignment by matching image-to-text generation with text-to-text generation that suffers less from exposure bias. The framework contains an image encoder, a text encoder and a text decoder. In training, images and paired reports are first encoded into image tokens and text tokens, and these tokens are randomly mixed to form the mixed tokens. Then, the text decoder accepts image tokens, text tokens or mixed tokens as prompt tokens and conducts text generation for network optimization. Furthermore, we introduce a tailored text decoder and an alternative training strategy that well integrate with our Token-Mixer framework. Extensive experiments across three publicly available datasets demonstrate Token-Mixer successfully enhances the image-text alignment and thereby attains a state-of-the-art performance. Related codes are available at https://github.com/yangyan22/Token-Mixer.

16.
Nat Commun ; 15(1): 4948, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862486

ABSTRACT

Seasonal storage of solar thermal energy through supercooled phase change materials (PCM) offers a promising solution for decarbonizing space and water heating in winter. Despite the high energy density and adaptability, natural PCMs often lack the necessary supercooling for stable, long-term storage. Leveraging erythritol, a sustainable mid-temperature PCM with high latent heat, we introduce a straightforward method to stabilize its supercooling by incorporating carrageenan (CG), a bio-derived food thickener. By improving the solid-liquid interfacial energy with the addition of CG the latent heat of erythritol can be effectively locked at a very low temperature. We show that the composite PCM can sustain an ultrastable supercooled state below -30 °C, which guarantees no accidental loss of the latent heat in severe cold regions on Earth. We further demonstrate that the common ultrasonication method can be used as the key to unlocking the latent heat stored in the CG-thickened erythritol, showing its great potential to serve as a high-performance, eco-friendly PCM for long-term seasonal solar energy storage.

17.
Sci Rep ; 14(1): 13367, 2024 06 11.
Article in English | MEDLINE | ID: mdl-38862693

ABSTRACT

Patients with distant metastasis of head and neck squamous cell carcinoma (HNSCC) often have a poor prognosis. However, early diagnosis of distant metastasis is challenging in clinical practice, and distant metastasis is often only detected in the late stages of tumor metastasis through imaging techniques. In this study, we utilized data from HNSCC patients collected from the TCGA database. Patients were divided into distant metastasis and nonmetastasis groups based on the tumor-node-metastasis (TNM) stage. We analyzed the differentially expressed genes between the two groups (DM/non-M DEGs) and their associated lncRNAs and generated a predictive model based on 23 lncRNAs that were significantly associated with the occurrence of distant metastasis in HNSCC patients. On this basis, we built a nomogram to predict the distant metastasis of HNSCC patients. Moreover, through WGCNA and Cytoscape software analysis of DM/non-M DEGs, we identified the gene most closely related to HNSCC distant metastasis: EIF5A. Our findings were validated using GEO data; EIF5A expression was significantly increased in the tumor tissues of HNSCC patients with distant metastasis. We then predicted miRNAs that can directly bind to EIF5A via the TargetScan and miRWalk websites, intersected them with differentially expressed miRNAs in the two groups from the TCGA cohort, and identified the only overlapping miRNA, miR-424; we predicted the direct binding site of EIF5A and miR-424 via the miRWalk website. Immunohistochemistry further revealed high expression of EIF5A in the primary tumor tissue of HNSCC patients with distant metastasis. These results provide a new perspective for the early diagnosis of distant metastasis in HNSCC patients and the study of the mechanisms underlying HNSCC distant metastasis.


Subject(s)
Eukaryotic Translation Initiation Factor 5A , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms , Neoplasm Metastasis , Nomograms , Peptide Initiation Factors , RNA-Binding Proteins , Squamous Cell Carcinoma of Head and Neck , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/pathology , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Peptide Initiation Factors/genetics , Peptide Initiation Factors/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Male , Female , RNA, Long Noncoding/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Gene Expression Profiling , Prognosis , Middle Aged
18.
Article in English | MEDLINE | ID: mdl-38843414

ABSTRACT

Objective: This study aims to investigate the efficacy of an Internet Plus-oriented 5A home care model in managing complications arising from tumor immunotherapy among patients in the post-epidemic era. Specifically, the study focuses on skin toxicity and gastrointestinal toxicity in patients undergoing tumor immunotherapy. Methods: Between January 2022 and March 2023, 80 patients experiencing skin and gastrointestinal toxicities post-tumor immunotherapy in Zhangjiagang Traditional Chinese Medicine Hospital were selected. The patients were divided into two groups: a control group and an experimental group, each comprising 40 patients. The control group received traditional routine nursing and a telephone follow-up strategy. In contrast, the experimental group was introduced to a 5A home care model guided by Internet Plus, involving five key stages of implementation. Nurses utilized the Internet Plus platform to provide timely responses to patient queries and concerns. After the intervention, skin and gastrointestinal toxicity grades were assessed on days 0, 7, 14, and 21. Additionally, the completion rates of immunotherapy follow-up were compared between the two groups. Results: At day 0, there was no statistically significant difference in skin and gastrointestinal toxicity grades between the two groups (P > .05). However, on days 7, 14, and 21, both groups showed improvements compared to day 0, with the experimental group exhibiting significantly better outcomes and lower toxicity grades than the control group (RR: 0.667, 95% CI (-1.204, 0.394)). The completion rate of immunotherapy in the experimental group (97.5%) was significantly higher than that in the control group (77.5%), with a notable statistical difference (RR:1.258, 95%CI (-0.258, 0.722), P = .004). In the control group, 4 patients refused treatment, and 4 voluntarily terminated treatment, whereas only 1 patient in the experimental group voluntarily terminated treatment. Conclusion: In conclusion, the Internet Plus-oriented 5A home care model enhances patient outcomes, demonstrating improved skin and gastrointestinal toxicities and a higher completion rate of immunotherapy compared to traditional nursing approaches. This model offers a more convenient and personalized health management approach, providing valuable insights for the clinical practice and future advancement of tumor immunotherapy.

19.
Signal Transduct Target Ther ; 9(1): 143, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38844468

ABSTRACT

Metastatic pancreatic cancer (mPC) has a dismal prognosis. Herein, we conducted a prospective, multicentre, single-arm, phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine (PAAG) in patients with first-line mPC (NCT05493995). The primary endpoints included the objective response rate (ORR) and disease control rate (DCR), while secondary endpoints encompassed progression-free survival (PFS), overall survival (OS), and safety. In 66 patients analysed for efficacy, the best response, indicated by the ORR, was recorded at 50.0% (33/66) (95% CI, 37.4-62.6%), with 33 patients achieving partial response (PR). Notably, the DCR was 95.5% (63/66, 95% CI, 87.3-99.1%). The median PFS (mPFS) and OS (mOS) were 8.8 (95% CI, 8.1-11.6), and 13.7 (95% CI, 12.4 to not reached) months, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 39.4% of patients (26/66). In prespecified exploratory analysis, patients with altered SWI/SNF complex had a poorer PFS. Additionally, low serum CA724 level, high T-cell recruitment, low Th17 cell recruitment, and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable efficacy. In conclusion, PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for mPC. The biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.


Subject(s)
Albumins , Antineoplastic Combined Chemotherapy Protocols , Deoxycytidine , Gemcitabine , Indoles , Paclitaxel , Pancreatic Neoplasms , Quinolines , Humans , Male , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Female , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Paclitaxel/pharmacology , Middle Aged , Aged , Deoxycytidine/analogs & derivatives , Deoxycytidine/administration & dosage , Indoles/administration & dosage , Indoles/therapeutic use , Albumins/administration & dosage , Albumins/adverse effects , Quinolines/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Prospective Studies , Adult , Neoplasm Metastasis , Angiogenesis Inhibitors/adverse effects , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/pharmacology , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/immunology
20.
Chem Biol Drug Des ; 103(6): e14557, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38825578

ABSTRACT

Recently, natural compounds such as quercetin have gained an increasing amount of attention in treating breast cancer. However, the exact mechanisms responsible for the antiproliferative functions of quercetin are not completely understood. Therefore, we aimed to examine quercetin impacts on breast cancer cell proliferation and survival and the involvement of PI3K/Akt/mTOR pathway. Breast cancer MDA-MB-231 and MCF-7 cells were exposed to quercetin, and cell proliferation was assessed by MTT assay. ELISA was applied to evaluate cell apoptosis. The expression levels of apoptotic mediators such as caspase-3, Bcl-2, Bax and PI3K, Akt, mTOR, and PTEN were assessed via qRT-PCR and western blot. We found that quercetin suppressed dose dependently cell growth capacity in MDA-MB-231 and MCF-7 cells. In addition, quercetin treatment increase apoptosis in both cells lines via modulating the pro- and antiapoptotic markers. Quercetin upregulated PTEN and downregulated PI3K, Akt, and mTOR, hence suppressing this signaling pathway in cells. In conclusion, we showed antiproliferative and pro-apoptotic function of quercetin in breast cancer cell lines, which is mediated by targeting and suppressing PI3K/Akt/mTOR signal transduction.


Subject(s)
Apoptosis , Breast Neoplasms , Cell Proliferation , Cell Survival , PTEN Phosphohydrolase , Proto-Oncogene Proteins c-akt , Quercetin , Signal Transduction , TOR Serine-Threonine Kinases , Quercetin/pharmacology , Humans , TOR Serine-Threonine Kinases/metabolism , PTEN Phosphohydrolase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Cell Proliferation/drug effects , Signal Transduction/drug effects , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Female , Cell Line, Tumor , Apoptosis/drug effects , Cell Survival/drug effects , MCF-7 Cells , Phosphatidylinositol 3-Kinases/metabolism
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