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1.
Cell Biol Int ; 47(11): 1843-1853, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37529875

ABSTRACT

Thyroid cancer is a prevalent form of endocrine cancer, and its global incidence has been steadily increasing. MEX3A is a protein that is known to be highly expressed in various human malignant tumors, including thyroid cancer, and it has been linked to patient prognosis. However, the molecular mechanisms underlying MEX3A's tumorigenic capabilities in thyroid cancer are not fully understood. In this study, we aimed to investigate the role of MEX3A in thyroid cancer. We confirmed that MEX3A was overexpressed in both thyroid cancer tissues and cell lines. Additionally, we found a positive correlation between high levels of MEX3A and the AJCC stage. To further understand the functional significance of MEX3A in thyroid cancer, we depleted MEX3A expression in B-CPAP and TPC-1 cells. Interestingly, we observed a significant reduction in thyroid cancer cell proliferation and migration, as well as ameliorated cell apoptosis and arrested tumor growth upon MEX3A depletion. These findings strongly suggested that MEX3A played a critical role in the development of thyroid cancer. Furthermore, our study uncovered an important interaction between MEX3A and CREB1 (cAMP response element-binding protein 1). The interaction between MEX3A and CREB1 appeared to contribute to the tumor-promoting effects of MEX3A in thyroid cancer by directly targeting CREB1. Silencing CREB1 was observed to alleviate the malignant phenotypes promoted by MEX3A in thyroid cancer cells. Together, this study highlighted the importance of the MEX3A-CREB1 interaction in thyroid cancer development and suggested the therapeutic potential of targeting MEX3A for the treatment of this disease.


Subject(s)
Thyroid Neoplasms , Humans , Cell Line, Tumor , Cell Proliferation , Cyclic AMP Response Element-Binding Protein/metabolism , Gene Expression Regulation, Neoplastic , Phosphoproteins/metabolism , RNA-Binding Proteins/metabolism
2.
Anal Bioanal Chem ; 415(5): 953-960, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36571589

ABSTRACT

Recently, nanozymes based on polymer-stabilized gold nanoparticles (AuNPs) have attracted more and more attention on account of their polymer-ligands' multiple functionalization sites. However, the contribution of polymer hydrogen bonding to the catalytic activity of AuNPs has received little attention. This study designed and fabricated poly(N-2-hydroxypropylmethacrylamide)-capped AuNPs (PHPAM@AuNPs) using a hydroxyl-rich polymer as the ligand. The PHPAM@AuNPs exhibited good peroxidase-mimicking activity capable of efficiently oxidizing 3,3'5,5'-tetramethylbenzidine (TMB) with H2O2. The effect of PHPAM hydrogen bonding on the catalytic activity of PHPAM@AuNPs was investigated. Under peroxidase-mimicking catalysis, homocysteine introduced a notable reduction in oxidation, allowing the creation of a colorimetric method for homocysteine detection with high selectivity and sensitivity. The ultraviolet-visible absorption intensity of oxidized TMB showed a strong linear relationship with homocysteine concentration in the range of 3.0-20.0 µM (R2 = 0.998), with a limit of detection of 0.4 µM. The proposed colorimetric protocol was used to monitor homocysteine in rat serum following intraperitoneal injection. This work provides a new way to refine AuNP-based nanozymes by relying on polymer-ligand hydrogen bonding. It has strong application potential in the analysis of endogenous molecules in real samples.


Subject(s)
Homocysteine , Metal Nanoparticles , Peroxidase , Animals , Rats , Colorimetry/methods , Coloring Agents , Gold , Hydrogen Peroxide/analysis , Ligands , Peroxidases , Polymers , Homocysteine/blood
3.
Cell Mol Biol (Noisy-le-grand) ; 69(4): 70-74, 2023 Apr 30.
Article in English | MEDLINE | ID: mdl-37329546

ABSTRACT

It was to investigate the mechanism of Maspin gene methylation induced by specific shRNA primer sequences in the proliferation of oral squamous cell carcinoma (OSCC) cells. Human OSCC HN13 cell line was selected as the study object, and the corresponding specific shRNA primer sequences were designed to construct Maspin-shRNA recombinant adenovirus using human Maspin nucleotide sequences as the target gene, and it was transfected into HN13 cells. The growth curve, Maspin expression level, migration and invasion ability, and proliferation activity of the transfected cells were analyzed. The results showed that the growth efficiency of transfected cells was significantly improved, and the OD value at 450 nm of cells in the specific sequence group (SSG) was greater than that of cells in the non-specific sequence group (nSSG). Maspin methylation was higher in the SSG than in the nSSG (P < 0.05). The number of cell migration and invasion in the SSG were higher than those in the nSSG (P < 0.05). The proliferation activity of cells in the SSG was higher than that of cells in the nSSG (P < 0.05). It showed that specific shRNA sequences induced Maspin gene methylation to inhibit Maspin expression, thereby participating in the migration and invasion motility of oral squamous carcinoma cells and improving proliferative activity.


Subject(s)
Mouth Neoplasms , Serpins , Squamous Cell Carcinoma of Head and Neck , Humans , Cell Line, Tumor , Cell Proliferation/genetics , Methylation , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , RNA, Small Interfering/genetics , Serpins/genetics , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/pathology
4.
Surg Endosc ; 37(2): 1173-1180, 2023 02.
Article in English | MEDLINE | ID: mdl-36149506

ABSTRACT

BACKGROUND: Portal vein tumor thrombosis (PVTT) secondary to primary liver carcinoma (PLC) is commonly associated with poor prognosis and poses great challenge. This study was to evaluate the efficacy and safety of percutaneous endovascular radiofrequency ablation (RFA) in treatment of PVTT. METHODS: Consecutive patients who were performed endovascular RFA because of PVTT in single-institution in recent 8 years were retrospectively reviewed, compared with patients who underwent only sequential transcatheter arterial chemoembolization (TACE) during the contemporary period. Patency of portal vein, complications, and overall survival (OS) were investigated. RESULTS: One hundred and 20 patients who underwent endovascular RFA and 96 patients who underwent only sequential TACE were included. No severe complications happened in both groups. Except the higher rates of severe fever and moderate pain in the study group, no difference was found in the incidence of side effects and complications. The effective rate in the study group was (78.3%, 94/120) significantly higher than the comparison group (35.4%, 34/96). The median survival time and 1-3 years cumulative survival rates in the study group were 15.7 months and 42.5%, 21.7%, 2.5%, respectively, and 11.3 months, 21.9%, 9.4%, 0 correspondingly in the comparison group, without significant difference. Type of PVTT and Child-Pugh classification of liver function were independent risk factors, and OS was significantly improved by endovascular RFA and subsequent therapy. CONCLUSION: Endovascular RFA is technically safe and feasible for unresectable PLC and PVTT to improve the prognosis and quality of life.


Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Radiofrequency Ablation , Thrombosis , Venous Thrombosis , Humans , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Portal Vein/pathology , Retrospective Studies , Quality of Life , Treatment Outcome , Thrombosis/complications , Combined Modality Therapy
5.
Cell Mol Life Sci ; 79(7): 377, 2022 Jun 23.
Article in English | MEDLINE | ID: mdl-35737114

ABSTRACT

We aimed to study mechanisms controlling metastatic outgrowth of melanoma into clinically relevant lesions, a critical process responsible for the majority of melanoma deaths. To this end, we developed novel in vivo models and identified molecular events that can be ascribed to their distinct phenotypes, indolent or highly metastatic. Induction of a proliferative state at distant sites was associated with high levels of the stem-like/progenitor marker, SOX2, and required the upregulation of FMOD, an extracellular matrix component, which modulates tumor-stroma interactions. Functional studies revealed a possible link between FMOD and SOX2; dual FMOD and SOX2 silencing nearly abolished brain metastasis and had a similar effect on distant metastasis to other sites. Our in vitro data suggests that FMOD and SOX2 cooperation plays an important role in tumor vasculogenic mimicry. Furthermore, we found that FMOD and SOX2 functional roles might converge at the activation of transcriptional co-factors YAP and TAZ, possibly via crosstalk with the tumor suppressor Hippo pathway. Finally, high expression of both genes in patient specimens predicted early development of brain metastasis. Thus, our study identifies FMOD and SOX2 cooperation as a novel regulatory mechanism that might be linked functionally to melanoma metastatic competence.


Subject(s)
Melanoma , Brain Neoplasms/secondary , Fibromodulin/genetics , Fibromodulin/metabolism , Humans , Melanoma/genetics , Neoplasm Metastasis , SOXB1 Transcription Factors/genetics , SOXB1 Transcription Factors/metabolism , Signal Transduction/physiology , Transcription Factors/genetics
6.
J Environ Manage ; 325(Pt B): 116533, 2023 Jan 01.
Article in English | MEDLINE | ID: mdl-36308957

ABSTRACT

Urban ecological environment is the basis of citizens' survival and development. A rapid and objective urban ecological environment assessment (UEEA) plays an important role in the urban sustainable development and environment protection. This study established an improved urban ecological comfort index (UECIIMP), which is based on our previous UECI and fully composed of four remote sensing indicators: normalized difference vegetation index (NDVI), normalized difference built-up index (NDBI), land surface temperature (LST), and aerosol optical depth (AOD), representing the greenness, dryness, heat, and atmospheric turbidity, respectively. Combining the entropy method and random forest (RF) algorithm, the weights of four indicators were calculated. To improve the accuracy of UECIIMP, the gap-filled quarterly mean results of each indicator with 30m resolution were obtained using the harmonic analysis of time series (HANTS) method and spatial-temporal information fusion based on non-local means filter (STNLFFM). UECIIMP was applied to the Hefei-Nanjing-Hangzhou Region to explore its spatiotemporal changes and response characteristics. Results show that the weights of UECIIMP fluctuate slightly (within 10%) before and after sensitivity analysis, with good stability and reliability. UECIIMP in Hangzhou > Hefei ≈ Nanjing, spring ≈ autumn > summer â‰« winter. From 2009 to 2019, UECIIMP has improved in all 33 districts of the Hefei-Nanjing-Hangzhou Region. The significant improvement of UECIIMP in 2014-2019 is 4.3 times than that in 2009-2014. The correlation between UECIIMP and economic index indicates that economic development has a positive impact on the urban ecological environment. The significant degradation of UECIIMP in the urban expansion area demonstrates a negative impact on the local environment from urban expansion.


Subject(s)
Environmental Monitoring , Remote Sensing Technology , China , Cities , Entropy , Environmental Monitoring/methods , Machine Learning , Reproducibility of Results
7.
Signal Process Image Commun ; 116: 116985, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37361462

ABSTRACT

In the context of COVID-19 pandemic prevention and control, it is of vital significance to realize accurate face mask detection via computer vision technique. In this paper, a novel attention improved Yolo (AI-Yolo) model is proposed, which can handle existing challenges in the complicated real-world scenarios with dense distribution, small-size object detection and interference of similar occlusions. In particular, a selective kernel (SK) module is set to achieve convolution domain soft attention mechanism with split, fusion and selection operations; a spatial pyramid pooling (SPP) module is applied to enhance the expression of local and global features, which enriches the receptive field information; and a feature fusion (FF) module is utilized to promote sufficient fusions of multi-scale features from each resolution branch, which adopts basic convolution operators without excessive computational complexity. In addition, the complete intersection over union (CIoU) loss function is adopted in the training stage for accurate positioning. Experiments are carried out on two challenging public face mask detection datasets, and the results demonstrate the superiority of the proposed AI-Yolo against other seven state-of-the-art object detection algorithms, which achieves the best results in terms of mean average precision and F1 score on both datasets. Furthermore, effectiveness of the meticulously designed modules in AI-Yolo is validated through extensive ablation studies. In a word, the proposed AI-Yolo is competent to accomplish face mask detection tasks under extremely complex situations with precise localization and accurate classification.

8.
J Cell Mol Med ; 26(1): 202-215, 2022 01.
Article in English | MEDLINE | ID: mdl-34859578

ABSTRACT

This study explored the role played by combined ICA and bone mesenchymal stem cells (BMSCs) in repairing rabbit knee cartilage defects. Firstly, rabbit BMSCs were isolated and used to construct an in vitro cellular model of oxygen-glucose deprivation/reoxygenation (OGD/R). Subsequently, ICA processing, Alcian blue staining, immunofluorescence and Western blot studies were performed to evaluate the ability of BMSCs to display signs of chondrogenic differentiation. Furthermore, a rabbit knee cartilage injury model was established in vivo. International Cartilage Repair Society (ICRS) macroscopic evaluations, H&E, Alcian blue and EdU staining, as well as immunohistochemistry, were analysed cartilage repair and pathological condition of the knee cartilage tissue. Our in vitro results showed that ICA promoted the chondrogenic differentiation of BMSCs, as well as aggrecan (AGR), bone morphogenetic protein 2 (BMP2) and COL2A1 protein expression in BMSCs. In vivo experiments showed that rabbits in the BMSCs or ICA treatment group had higher ICRS scores and displayed a better restoration of cartilage-like tissue and chondrocyte expression on the surface of their cartilage defects. In conclusion, ICA or BMSCs alone could repair rabbit knee cartilage damage, and combined treatment with ICA and BMSCs showed a better ability to repair rabbit knee cartilage damage.


Subject(s)
Cartilage, Articular , Mesenchymal Stem Cells , Animals , Bone Marrow Cells/metabolism , Cartilage, Articular/pathology , Cell Differentiation , Cells, Cultured , Chondrogenesis/genetics , Flavonoids , Glucose/metabolism , Mesenchymal Stem Cells/metabolism , Oxygen/metabolism , Oxygen/pharmacology , Rabbits
9.
Br J Cancer ; 126(11): 1581-1588, 2022 06.
Article in English | MEDLINE | ID: mdl-35165401

ABSTRACT

BACKGROUND: CD103+CD8+ tissue-resident memory T (TRM) cells, associated with better overall survival among various malignancies, are thought to activate anti-tumour immune response and affect therapeutic sensitivity including both immunotherapy and adjuvant chemotherapy (ACT). METHODS: Totally 650 muscle-invasive bladder cancer (MIBC) patients from three independent cohorts were included in this study for survival and cisplatin-based ACT response analysis. Another public data set consisting of 195 patients from IMvigor210 trial receiving PD-L1 blockade were involved in the assessment of immunotherapeutic response. Fifty-nine fresh tumour tissues were used to evaluate immune infiltration of CD103+CD8+ TRM cells. RESULTS: Patients with high CD103+CD8+ TRM cells infiltration, but not CD8+ T cells, are more likely to benefit from immunotherapy and ACT. The presence of TRM cells is highly associated with an enhanced IFNγ-enriched and T cell-inflamed anti-tumour microenvironment. Elevated CD103+CD8+ TRM cells infiltration correlated with superior ACT response in mismatch repair (MMR), homologous recombination (HR), PIK3CA/AKT and RAS/RAF pathway proficient or histone modification and cell cycle pathway deficient patients. CONCLUSIONS: CD103+CD8+ TRM cells played a crucial role in anti-tumour immunity and served as an ideal prognostic biomarker. It could be treated as a superior companion predictor for treatment response to PD-L1 inhibitor and ACT within MIBC patients.


Subject(s)
Urinary Bladder Neoplasms , CD8-Positive T-Lymphocytes , Humans , Immunologic Memory , Lymphocytes, Tumor-Infiltrating , Memory T Cells , Muscles/metabolism , Muscles/pathology , Tumor Microenvironment , Urinary Bladder Neoplasms/drug therapy
10.
Br J Cancer ; 126(9): 1310-1317, 2022 05.
Article in English | MEDLINE | ID: mdl-35039625

ABSTRACT

BACKGROUND: TIGIT and PD-1 are checkpoint receptors that could regulate the functional status of immune cells through independent pathways. However, the clinical significance of immune classification based on TIGIT and PD-1 expression remains unclear in muscle-invasive bladder cancer (MIBC). METHODS: Patients with MIBC from four independent cohorts were categorised into three clusters. Survival analysis conducted through Kaplan-Meier curves and Cox regression model. Immune contexture was measured by immunohistochemistry and CIBERSORT algorithm. Twenty-five fresh tumour tissue samples were utilised to evaluate functional state of CD8+ T cells by flow cytometry. RESULTS: Cluster I (TIGITlowPD-1low) contained widely poor immune infiltrates with higher FGFR3 mutation, Cluster II (TIGITlowPD-1high) exhibited a highly infiltrated contexture with increased cytolytic CD8+ T cells and had the best prognosis, Cluster III (TIGIThigh) presented a suppressive tumour microenvironment (TME) featured by exhausted CD8+ T cells and basal molecular subtype. Patients of Cluster III had the worst survival but could benefit more from adjuvant chemotherapy and anti-PD-L1 immunotherapy, and also presented limited FGFR3 signalling signature but activated immunotherapeutic and EGFR-associated pathway. CONCLUSIONS: TIGIT/PD-1-based risk stratification with distinct immune and molecular features could be served as a predictor for systematic therapeutic response including adjuvant chemotherapy and immunotherapy in MIBC patients.


Subject(s)
Urinary Bladder Neoplasms , B7-H1 Antigen/metabolism , CD8-Positive T-Lymphocytes , Chemotherapy, Adjuvant , Female , Humans , Male , Muscles/metabolism , Muscles/pathology , Prognosis , Programmed Cell Death 1 Receptor/metabolism , Receptors, Immunologic/genetics , Retrospective Studies , Tumor Microenvironment/genetics , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology
11.
Cancer Immunol Immunother ; 71(6): 1497-1506, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34716763

ABSTRACT

BACKGROUND: Muscle-invasive bladder cancer (MIBC) is an aggressive and heterogeneous malignancy. Tumor-associated macrophages (TAMs) are key infiltrating cell populations in the inflammatory microenvironment of malignant tumors including MIBC. It intrigues us to explore the clinical significance and immunoregulatory role of TAMs infiltration and polarization in MIBC. METHODS: A total of 141 patients with MIBC from Zhongshan Hospital and 391 patients with MIBC from The Cancer Genome Atlas (TCGA) database were included in this study. Moreover, 195 patients who received anti-PD-L1 therapy from the IMvigor210 trial were enrolled. Patients were categorized into three subtypes considering the infiltration level and polarization status of TAMs, denoted as TAMlow (Subtype I), TAMhigh&M2/M1low (Subtype II), and TAMhigh&M2/M1high (Subtype III). RESULTS: Subtype III suffered inferior prognosis, and Subtype II could benefit more from adjuvant chemotherapy (ACT). Subtype III was featured with increased pro-tumor cells and immunosuppressive cytokines, while Subtype II possessed more immunogenic cells infiltration with activated and tumoricidal properties. Subtype II and Subtype III presented basal/squamous-like characterization and showed additional prognostic merit beyond molecular classification. Subtype I exhibited elevated level of FGFR3 signature, while Subtype II had EGFR signaling activation and immunotherapeutic indication. Additionally, Subtype II patients were indeed highly sensitive to PD-L1 blockade therapy in IMvigor210 trial. CONCLUSION: The infiltration and polarization status of TAMs shaped distinct immune microenvironment with predictive significance for survival outcome, ACT benefit, and PD-L1 blockade therapy sensitivity in MIBC. Immune classification based on TAMs polarization and infiltration might provide tools to tailor chemotherapy and immunotherapy.


Subject(s)
Urinary Bladder Neoplasms , B7-H1 Antigen/therapeutic use , Humans , Muscles/pathology , Prognosis , Tumor Microenvironment , Tumor-Associated Macrophages , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/genetics
12.
Cancer Immunol Immunother ; 71(2): 301-310, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34152439

ABSTRACT

BACKGROUND: Latency-associated peptide (LAP) was identified as crucial immune regulator in tumor microenvironment (TME) in recent researches. In this study, we aimed to estimate the predictive value of LAP expression for clinical survival and therapeutic response in muscle-invasive bladder cancer (MIBC). METHODS: Our study encompassed 140 MIBC patients from Zhongshan Hospital (ZSHS cohort), 401 patients from The Cancer Genome Atlas (TCGA cohort) and 195 patients received PDL1 blockade from IMvigor210 trial. Survival analyses were conducted through Kaplan-Meier curve and Cox regression model. LAP expression and its association with immune contexture were evaluated in ZSHS and TCGA cohort. RESULTS: We found that high intratumoral LAP+ cells infiltration anticipated inferior survival and adjuvant chemotherapy (ACT) response, and was closely related to an immunoevasive contexture with increased M2 macrophages, neutrophils and conspicuously a cluster of highly exhausted CD8+ T cells. The combinational analysis of LAP+ cells and CD8+ T cells infiltration stratified patients into distinct risk groups with implications for therapeutic sensitivity to PDL1 blockade and refinement of molecular classification in MIBC. CONCLUSIONS: LAP expression was correlated with patients' inferior prognosis, ACT-tolerance and an immunoevasive TME with exhausted CD8+ T cell infiltration, suggesting that LAP could serve as a promising therapeutic target in MIBC. Simultaneously, our novel TME classification based on LAP+ cells and CD8+ T cells infiltration and its potential in appraising PDL1 blockade application for MIBC patients deserved further validation.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Chemotherapy, Adjuvant/mortality , Drug Resistance, Neoplasm , Muscle Neoplasms/pathology , Peptides/metabolism , Protein Precursors/metabolism , Transforming Growth Factor beta/metabolism , Tumor Microenvironment , Urinary Bladder Neoplasms/pathology , Follow-Up Studies , Humans , Immune Checkpoint Inhibitors/pharmacology , Muscle Neoplasms/drug therapy , Muscle Neoplasms/immunology , Muscle Neoplasms/metabolism , Prognosis , Retrospective Studies , Survival Rate , Tumor Escape , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/immunology , Urinary Bladder Neoplasms/metabolism
13.
Cancer Immunol Immunother ; 71(9): 2117-2126, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35041031

ABSTRACT

BACKGROUND: Immune checkpoint blockade (ICB) and adjuvant chemotherapy (ACT) have shown clinical benefit in muscle-invasive bladder cancer (MIBC) with only a few predictive biomarkers identified so far. Neuropilin-1 (NRP1) has been identified as a key immune checkpoint and a novel immunotherapeutic target but the clinical significance of NRP1 remains unclear in MIBC. METHODS: Three independent cohorts were involved in our study: IMvigor210 Cohort (n = 348), The Cancer Genome Atlas Cohort (TCGA, n = 391), and Zhongshan Hospital Cohort (ZSHS, n = 130). Parallel detection and validation of risk stratification based on NRP1 expression were executed in patients treated with anti-PD-L1 agent and adjuvant chemotherapy (ACT). RESULTS: NRP1 expression conferred poor survival and predicted response to both PD-L1 blockade and cisplatin-based ACT in MIBC. Further exploration revealed high-level NRP1 was extremely associated with infiltration of exhausted CD8+ T cells, immature NK cells and M2 polarized tumor-associated macrophages in MIBC patients. Moreover, elevated NRP1 expression was also correlated with low mutation burden and reduced mutation in cell cycle pathway. CONCLUSIONS: Our study firstly identified and validated the clinical implications of NRP1 expression for prognosis and systematic therapeutic responses (PD-L1 blockade and ACT) in MIBC. NRP1 expression was associated with an immunosuppressive microenvironment with dysfunctional effector immune cells. Prospective investigations of its roles in the therapeutic landscape of MIBC warrant more consideration.


Subject(s)
Neuropilin-1 , Urinary Bladder Neoplasms , CD8-Positive T-Lymphocytes , Humans , Muscles/metabolism , Neoplasm Invasiveness , Neuropilin-1/genetics , Prognosis , Prospective Studies , Tumor Microenvironment , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/therapy
14.
Ann Surg Oncol ; 29(4): 2495-2503, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35000080

ABSTRACT

BACKGROUND: This study aims to reveal the clinical significance of stromal-infiltrating tumor-associated macrophages (TAMs) in muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS: This study included 288 patients from the TCGA database and 118 patients from Fudan University Shanghai Cancer Center with MIBC. The CIBERSORT model and immunohistochemistry were used to evaluate TAM infiltration. Cox regression analyses were employed to calculate their prognostic value. RESULTS: Among all 23 immune phenotypes analyzed in the TCGA cohort, pan-macrophage infiltration was significantly associated with poor prognosis (p = 0.001). Further analyses found that stromal TAM infiltration could be an independent prognostic predictor for recurrence-free survival (RFS; HR: 1.019, 95% CI: 1.006-1.033, p = 0.004). High stromal infiltration was related to unfavorable RFS. After stratification by adjuvant chemotherapy (ACT), patients without ACT could be differentiated by TAM infiltration (p = 0.036), while patients with ACT could not. Moreover, TAM infiltration was negatively associated with IFN-γ-related mRNA panel, which was shown to have strong predictive value for clinical response to programmed death-1 (PD-1) inhibition. CONCLUSIONS: Stromal TAM infiltration could be an independent prognosticator for MIBC patients. This might have potential to guide precise treatments such as ACT and immune checkpoint blockade in MIBC.


Subject(s)
Urinary Bladder Neoplasms , China , Humans , Muscles , Prognosis , Tumor-Associated Macrophages , Urinary Bladder Neoplasms/drug therapy
15.
Opt Lett ; 47(2): 218-221, 2022 Jan 15.
Article in English | MEDLINE | ID: mdl-35030571

ABSTRACT

Chip-level spectrometers provide a stable and cost-effective solution for spectral analysis in various applications. Here we present a silicon on-chip digital Fourier transform spectrometer consisting of eight cascaded optical switches connected by delay waveguides. By configuring the states of the optical switches, this chip can realize 127 Mach-Zehnder interferometers with linearly increased optical path differences. A machine-learning regularization method is utilized to reconstruct the spectrum. Experimental results show that our chip can retrieve both sparse and broadband optical spectra with negligible reconstruction errors. The spectral resolution can be further improved by cascading more stages of optical switches. Our method has the advantages of compact size, high scalability, and high signal-to-noise ratio, making it a promising candidate for realizing miniaturized spectrometers.

16.
Phys Rev Lett ; 129(15): 151101, 2022 Oct 07.
Article in English | MEDLINE | ID: mdl-36269963

ABSTRACT

Interacting massive spin-1 fields have been widely used in cosmology and particle physics. We obtain a new condition on the validity of the classical limit of these theories related to the nontrivial constraints that exist for vector field components. A violation of this consistency condition causes a singularity in the time derivative of the auxiliary component and could impact, for example, the field's cosmic history and superradiance around black holes. We show that gauge-invariant interactions are generally safe from this problem, even though the mass term explicitly breaks the gauge symmetry. Such restrictions for interactions are expected to exist generically in many other nontrivially constrained systems.

17.
Analyst ; 147(7): 1509-1514, 2022 Mar 28.
Article in English | MEDLINE | ID: mdl-35293403

ABSTRACT

More recently, gold nanoparticle (AuNP)-based nanozymes have become one of the burgeoning research hot topics. However, few studies have focused on these AuNP-nanozymes with polymers as ligands. A significant challenge is to reveal their catalytic mechanism and to improve their catalytic activity by changing the structures of the polymers. In this study, polyacrylamide (PAM) with different chain lengths was synthesized and used as the ligand to prepare PAM@AuNPs. The resultant nanozymes exhibited good peroxidase-like activity for catalyzing the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide (H2O2). In particular, due to the electrostatic interaction between the negatively charged PAM@AuNPs and the positively charged drug, the addition of ciprofloxacin in the oxidation system induced the aggregation of PAM@AuNPs and produced more amount of reactive oxygen species, which greatly promoted the catalytic activity of PAM@AuNPs. Inspired by the attractive property, a highly selective and sensitive colorimetric assay for the monitoring of ciprofloxacin was created. A good linear relationship between the UV-Vis absorption intensity of PAM@AuNPs-TMB-H2O2 at 650 nm wavelength and the ciprofloxacin concentration was observed ranging from 1.0 µM to 12.0 µM (R2 = 0.998), providing the detection limit of 0.5 µM. The ciprofloxacin metabolism was further studied in rats. It reveals great potential of polymer protected AuNP-nanozymes in practical drug analysis.


Subject(s)
Gold , Metal Nanoparticles , Animals , Ciprofloxacin , Gold/chemistry , Hydrogen Peroxide/chemistry , Metal Nanoparticles/chemistry , Polymers , Rats
18.
Surg Endosc ; 36(3): 1789-1798, 2022 03.
Article in English | MEDLINE | ID: mdl-33788032

ABSTRACT

BACKGROUND: Although self-expandable mental stents (SEMS) placement is the standard care for relieving obstructive jaundice caused by unresectable malignant biliary stricture, how to maintain stent potency remains an intractable problem. This study was to evaluate the efficacy and safety of endobiliary radiofrequency ablation (RFA) through percutaneous transhepatic cholangiography (PTC) pathway in treating such patients. METHODS: Consecutive patients who were performed endobiliary RFA as well as SEMS placement because of unresectable malignant obstructive jaundice in single institution in recent 8 years were retrospectively reviewed. As comparison, patients who underwent only percutaneous SEMS placement for unresectable malignant biliary stricture during the contemporary period were reviewed. Stent patency, complications, complications, and overall survival (OS) were investigated and analyzed. RESULTS: One hundred and fifty patients who underwent endobiliary RFA and 127 patients who underwent only stent placement were included in this study. In the study group of endobiliary RFA, 87 patients (58.0%) underwent ablation for 1 time, 49 (32.7%) for 2 times, and 14 (9.3%) for 3 times. Complications related to RFA as well as SEMS placement happened in 113 patients (75.3%), without severe complications that needed emergent surgery or interventional therapy. The median duration of stent patency after ablation was 11.2 month, and the median survival time was 12.3 month. As comparison, difference was found in the number of interventional procedures and stents placed, duration of initial stent patency, and the incidence of moderate bleeding and pain. In the study group, only the type of tumor that caused biliary obstruction (intrahepatic carcinoma vs. extrahepatic carcinoma) was a poor independent factor (P = 0.035) for recurrent biliary obstruction. Repeated interventional therapy and adoption of subsequent therapy were only independent factors for OS. CONCLUSIONS: Endobiliary RFA and SEMS placement is technically safe and feasible for unresectable malignant obstructive jaundice to improve the quality of life and prolong survival.


Subject(s)
Bile Duct Neoplasms , Catheter Ablation , Cholestasis , Jaundice, Obstructive , Radiofrequency Ablation , Bile Duct Neoplasms/complications , Bile Duct Neoplasms/surgery , Catheter Ablation/methods , Cholestasis/etiology , Cholestasis/surgery , Humans , Jaundice, Obstructive/etiology , Jaundice, Obstructive/surgery , Quality of Life , Radiofrequency Ablation/adverse effects , Retrospective Studies , Stents/adverse effects , Treatment Outcome
19.
World J Surg Oncol ; 20(1): 324, 2022 Sep 29.
Article in English | MEDLINE | ID: mdl-36175920

ABSTRACT

BACKGROUND: Transurethral resection of the bladder tumor (TURBT) is one of the most established urological procedures for the treatment of the primary non-muscle-invasive bladder cancer (NMIBC). The aim of the study is to evaluate the efficacy and safety of 980 nm diode laser as a treatment for primary NMIBC. METHODS: Eighty-eight patients with NMIBC were treated by en bloc transurethral resection with 980 nm diode laser, and 76 patients were treated by plasmakinetic transurethral resection from May 2016 to July 2019 at the Department of Urology, Tangdu Hospital, Air Force Medical University. The clinical data were collected and compared between the two groups. RESULTS: The bladder irrigation time was shortened in 980 nm diode laser group compared to that of plasmakinetic transurethral resection group (4.1 ± 0.6 vs 13.1 ± 3.1 h, p < 0.001). A total of 13.2% (10/76) patients experienced obturator nerve reflex, and 5.3% (4/76) experienced delayed bleeding in plasmakinetic transurethral resection group, while no obturator nerve reflex and delayed bleeding cases were observed in 980 nm diode laser group (p < 0.05). The postoperative catheterization and hospitalization time showed no significant difference between the two groups. The median follow-up time was 27 months (13-38 months). No significant difference in the recurrence rate was observed between the two groups. CONCLUSIONS: The 980 nm diode laser is an effective and safe tool in transurethral resection of NMIBC using en bloc technique. It has less perioperative complications and shortened bladder irrigation time.


Subject(s)
Urinary Bladder Neoplasms , Cystectomy/methods , Humans , Lasers, Semiconductor/therapeutic use , Operative Time , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/surgery , Urologic Surgical Procedures/methods
20.
Entropy (Basel) ; 24(12)2022 Dec 10.
Article in English | MEDLINE | ID: mdl-36554210

ABSTRACT

In the process of bridge management, large amounts of domain information are accumulated, such as basic attributes, structural defects, technical conditions, etc. However, the valuable information is not fully utilized, resulting in insufficient knowledge service in the field of bridge management. To tackle these problems, this paper proposes a complex knowledge base question answering (C-KBQA) framework for intelligent bridge management based on multi-task learning (MTL) and cross-task constraints (CTC). First, with C-KBQA as the main task, part-of-speech (POS) tagging, topic entity extraction (TEE), and question classification (QC) as auxiliary tasks, an MTL framework is built by sharing encoders and parameters, thereby effectively avoiding the error propagation problem of the pipeline model. Second, cross-task semantic constraints are provided for different subtasks via POS embeddings, entity embeddings, and question-type embeddings. Finally, using template matching, relevant query statements are generated and interaction with the knowledge base is established. The experimental results show that the proposed model outperforms compared mainstream models in terms of TEE and QC on bridge management datasets, and its performance in C-KBQA is outstanding.

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