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1.
Quant Imaging Med Surg ; 14(9): 6362-6373, 2024 Sep 01.
Article de Anglais | MEDLINE | ID: mdl-39281141

RÉSUMÉ

Background: In many clinical situations, it is critical to exclude or identify abnormally lymph nodes (LNs). The nature of superficial abnormally LNs is closely related to the stage, treatment, and prognosis of the disease. Ultrasound (US) is an important method for examining superficial LNs due to its cheap and safe characteristics. However, it is still difficult to determine the nature of some LNs with overlapping benign and malignant features in images. Contrast-enhanced ultrasound (CEUS) can be used to evaluate the microperfusion status of tissues in real time, and it can improve diagnostic accuracy to a certain extent. Therefore, in this study, we will analyze the correlation between CEUS quantitative parameters and benign and malignant superficial abnormally LNs, to evaluate the efficacy and value of CEUS in distinguishing benign and malignant superficial LNs. Methods: This study retrospectively analyzed 120 patients of abnormal LNs who underwent US and CEUS at the China-Japan Union Hospital of Jilin University from December 2020 to August 2023. All 120 cases of abnormal LNs underwent US-guided coarse needle biopsy, and accurate pathological results were obtained, along with complete US and CEUS images. According to the pathological results, LNs were divided into benign and malignant groups, and the qualitative and quantitative parameters of US and CEUS between the two groups were analyzed. The cutoff value is determined by the receiver operating characteristic (ROC) curve of the subjects, and sensitivity, specificity, and accuracy are applied to evaluate the ability of the cutoff value to distinguish between the two groups. Results: There were a total of 120 LNs, including 36 in the benign group and 84 in the malignant group. The results showed that malignant LNs were usually characterized by the disappearance of lymphatic hilum, round ness index (L/T) <2, irregular morphology, and the manifestation of uneven perfusion (P<0.05). The differences in the quantitative parameters peak enhancement (PE), rise time (RT), time to peak (TTP), wash-in rate (WIR), and wash-out rate (WOR) were statistically significant (P<0.05). The result showed that RT and TTP in the malignant LNs were higher than those in the benign LNs, while the PE, WIR, and WOR were lower. A comparison of the ∆ values showed that the differences in ∆PE, ∆WIR, and ∆fall time (FT) were statistically significant (P<0.05), Among them, the ∆PE and ∆WIR of malignant LNs were higher than those of benign LNs, while the ∆FT was lower than that of benign LNs. Conclusions: Quantitative analysis of CEUS features is valuable in the diagnosis of benign and malignant LNs, and US combined with CEUS helps to improve the accuracy of identifying the nature of LNs.

2.
Materials (Basel) ; 17(17)2024 Aug 26.
Article de Anglais | MEDLINE | ID: mdl-39274609

RÉSUMÉ

The extrusion ratio (ER) is one of the most important factors affecting the service performance of aluminum profiles. In this study, the influence of ER on the mechanical behavior and microstructure evolution of 7003 aluminum alloy at high-speed impact with strain rates ranging from 700 s-1 to 1100 s-1 was investigated. The studied alloy with an ER of 56 formed coarse grain rings during the heat treatment. The microstructure of the alloys with ERs of 20 and 9 is relatively uniform. The results indicate that under high-speed impact, the mechanical response behavior of the 7003-T6 alloy with different ERs is different. For the alloy with an ER of 56, strain hardening is the main mechanism of plastic deformation. In contrast, a flow stress reduction occurs at middle deformation stage for the ones with ERs of 20 and 9 due to concentrated deformation, which is more significant in the alloy with an ER of 20. Under high-speed impact, the alloy with an ER of 56 undergoes uneven plastic deformation due to the presence of coarse grain rings. The deformation is mainly borne by the region of coarse grains near the edge, and the closer to the center, the smaller the deformation. The deformation of the alloys with ERs of 20 and 9 is relatively uniform, but exhibits localized concentrated deformation in the area near the edge. The significant plastic deformation within deformation band causes a local temperature rise, resulting in a slight decrease in flow stress after the peak. These results can provide reliable data support for the application of 7003 aluminum alloy in the vehicle body crash energy absorption structure.

3.
Sci Rep ; 14(1): 15907, 2024 07 10.
Article de Anglais | MEDLINE | ID: mdl-38987625

RÉSUMÉ

Agricultural social services (ASS) play an important role in improving the efficiency of agricultural operations, reducing agricultural production costs, and promoting sustainable agricultural development. Using data from the 2020 China Rural Revitalization Survey, this study analyzes the impact of ASS on reducing pesticide inputs. The results show: (1) ASS play a significantly positive role in reducing pesticide inputs. (2) Heterogeneity analyses show that ASS' role in reducing pesticide inputs is stronger for farming households with small farms, which participate in cooperatives, and do not have members involved in non-farm employment than that for farming households with large farms, which do not participate in cooperatives, and have members involved in non-farm employment. (3) Mechanism analysis shows that ASS' green perception and demonstration-led effects contribute to reducing pesticide inputs by 148.6% and 36.8%, respectively, at the 1% level. Finally, this study proposes relevant policy recommendations for promoting ASS, promoting the continuous operation of farmland, and encouraging farmers to participate in ASS.


Sujet(s)
Agriculture , Pesticides , Agriculture/méthodes , Humains , Chine , Services sociaux et travail social (activité) , Agriculteurs , Fermes , Population rurale , Enquêtes et questionnaires
4.
J Pathol ; 263(4-5): 454-465, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38845115

RÉSUMÉ

Gastric cancer (GC) is one of the most heterogeneous tumors. However, research on normal tissue adjacent to the tumor (NAT) is very limited. We performed multi-regional omics sequencing on 150 samples to assess the genetic basis and immune microenvironment in NAT and matched primary tumor or lymph node metastases. NATs demonstrated different mutated genes compared with GC, and NAT genomes underwent independent evolution with low variant allele frequency. Mutation profiles were predominated by aging and smoking-associated signatures in NAT instead of signatures associated with genetic instability. Although the immune microenvironment within NATs shows substantial intra-patient heterogeneity, the proportion of shared TCR clones among NATs is five times higher than that of tumor regions. These findings support the notion that subclonal expansion is not pronounced in NATs. We also demonstrated remarkable intra-patient heterogeneity of GCs and revealed heterogeneity of focal amplification of CD274 (encoding PD-L1) that leads to differential expression. Finally, we identified that monoclonal seeding is predominant in GC, which is followed by metastasis-to-metastasis dissemination in individual lymph nodes. These results provide novel insights into GC carcinogenesis. © 2024 The Pathological Society of Great Britain and Ireland.


Sujet(s)
Antigène CD274 , Mutation , Tumeurs de l'estomac , Microenvironnement tumoral , Humains , Tumeurs de l'estomac/génétique , Tumeurs de l'estomac/anatomopathologie , Tumeurs de l'estomac/immunologie , Microenvironnement tumoral/génétique , Microenvironnement tumoral/immunologie , Antigène CD274/génétique , Hétérogénéité génétique , Métastase lymphatique , Mâle , Femelle , Sujet âgé , Adulte d'âge moyen , Marqueurs biologiques tumoraux/génétique
5.
Cancer Lett ; 597: 216995, 2024 Aug 10.
Article de Anglais | MEDLINE | ID: mdl-38851313

RÉSUMÉ

Globally, breast cancer (BC) is the predominant malignancy with a significant death rate due to metastasis. The epithelial-mesenchymal transition (EMT) is a fundamental initiator for metastatic progression. Through advanced computational strategies, TCF19 was identified as a critical EMT-associated gene with diagnostic and prognostic significance in BC, based on a novel EMT score. Molecular details and the pro-EMT impact of the TCF19/miR-199a-5p/SP1/LOXL2 axis were explored in BC cell lines through in vitro validations, and the oncogenic and metastatic potential of TCF19 and LOXL2 were investigated using subcutaneous and tail-vein models. Additionally, BC-specific enrichment of TCF19 and LOXL2 was measured using a distribution landscape driven by diverse genomic analysis techniques. Molecular pathways revealed that TCF19-induced LOXL2 amplification facilitated migratory, invasive, and EMT activities of BC cells in vitro, and promoted the growth and metastatic establishment of xenografts in vivo. TCF19 decreases the expression of miR-199a-5p and alters the nuclear dynamics of SP1, modulating SP1's affinity for the LOXL2 promoter, leading to increased LOXL2 expression and more malignant characteristics in BC cells. These findings unveil a novel EMT-inducing pathway, the TCF19/miR-199a-5P/SP1/LOXL2 axis, highlighting the pivotal role of TCF19 and suggesting potential for novel therapeutic approaches for more focused BC interventions.


Sujet(s)
Amino-acid oxidoreductases , Tumeurs du sein , Transition épithélio-mésenchymateuse , Régulation de l'expression des gènes tumoraux , microARN , Facteur de transcription Sp1 , Humains , Transition épithélio-mésenchymateuse/génétique , Femelle , Tumeurs du sein/anatomopathologie , Tumeurs du sein/génétique , Tumeurs du sein/métabolisme , microARN/génétique , microARN/métabolisme , Facteur de transcription Sp1/métabolisme , Facteur de transcription Sp1/génétique , Animaux , Amino-acid oxidoreductases/génétique , Amino-acid oxidoreductases/métabolisme , Souris , Lignée cellulaire tumorale , Mouvement cellulaire , Métastase tumorale , Transduction du signal , Souris nude
6.
Front Med (Lausanne) ; 11: 1328719, 2024.
Article de Anglais | MEDLINE | ID: mdl-38799147

RÉSUMÉ

Background: To date, the correlation between CD4 on the monocytes (mCD4) expression and the prognosis of patients with septic shock remains unclear. The purpose of this study was to analyze the expression of mCD4 in these patients and further evaluate whether mCD4 expression correlates with either the recovery from multiple organ dysfunction syndrome (MODS) or mortality. Methods: The study participants were recruited from a tertiary general hospital in China (Affiliated Dongyang Hospital of Wenzhou Medical University). Sepsis and septic shock were diagnosed based on the diagnostic criteria of Sepsis-3. MODS was defined as a Sequential Organ Failure Assessment score of at least two organ systems ≥2. Persistent MODS was defined as the continual meeting of the MODS criteria when re-evaluated one week after admission (day 7). A logistic regression model was used to test whether mCD4 was an independent prognostic factor for mortality in patients with septic shock. A paired sample rank sum test was used to examine the correlation between mCD4 expression and MODS recovery. Result: The study recruited 79 patients with septic shock as the study group, 74 patients with sepsis as the disease control group, and 56 volunteers as healthy controls. In the first 24 h after admission (day 1), mCD4 expression was significantly reduced in patients with septic shock compared to healthy controls and patients with sepsis. Moreover, mCD4 expression was an independent prognostic factor for in-hospital and 28 day mortality in patients with septic shock. mCD4 expression did not show significant differences in patients with persistent MODS on day 7 compared to day 1. However, mCD4 expression was significantly higher in patients without persistent MODS on day 7 than on day 1. Conclusion: mCD4 expression is significantly reduced in patients with septic shock, which is an independent prognostic factor for mortality and closely related to recovery from MODS.

7.
Sci Rep ; 14(1): 12188, 2024 05 28.
Article de Anglais | MEDLINE | ID: mdl-38806640

RÉSUMÉ

Natural killer (NK) cells are closely associated with malignant tumor progression and metastasis. However, studies on their relevance in colorectal cancer (CRC) are limited. We aimed to comprehensively analyze the absolute counts, phenotypes, and function of circulating NK cells in patients with CRC using multiparametric flow cytometry. The distribution of NK cell subsets in the peripheral circulation of patients with CRC was significantly altered relative to the control group. This is shown by the decreased frequency and absolute count of CD56dimCD16+ NK cells with antitumor effects, contrary to the increased frequency of CD56bright NK and CD56dimCD16- NK cells with poor or ineffective antitumor effects. NK cells in patients with CRC were functionally impaired, with decreased intracellular interferon (IFN)-γ secretion and a significantly lower percentage of cell surface granzyme B and perforin expression. In addition, IFN-γ expression decreased significantly with the tumor stage progression. Based on a comprehensive analysis of the absolute counts, phenotypes, and functional markers of NK cells, we found an altered subset distribution and impaired function of circulating NK cells in patients with CRC.


Sujet(s)
Tumeurs colorectales , Granzymes , Interféron gamma , Cellules tueuses naturelles , Humains , Cellules tueuses naturelles/immunologie , Cellules tueuses naturelles/métabolisme , Tumeurs colorectales/immunologie , Tumeurs colorectales/anatomopathologie , Tumeurs colorectales/métabolisme , Tumeurs colorectales/sang , Mâle , Femelle , Adulte d'âge moyen , Interféron gamma/métabolisme , Sujet âgé , Granzymes/métabolisme , Perforine/métabolisme , Antigènes CD56/métabolisme , Cytométrie en flux , Adulte
8.
Sci Total Environ ; 928: 172520, 2024 Jun 10.
Article de Anglais | MEDLINE | ID: mdl-38631631

RÉSUMÉ

Drought is a global environmental problem, while the effect of drought-induced unsaturation on the fate of heavy metal ions is still poorly understood, particularly the lack of mechanistic information at the molecular level. This study used molecular dynamics simulations to investigate nanoscale interactions at the montmorillonite surface under different moisture conditions. Compared to the saturated condition, drought increased the amounts and strength of Cd2+ ions adsorbed on the montmorillonite (MMT) surface while decreased the diffusivity, which was especially obvious in extreme drought conditions (θv=21%-7%). This is closely related to the compressed electric double layer, overcompensation of surface charge, and increased ion pair interactions, resulting from the confinement of water films under drought stress. Further analysis showed that the decrease of hydration effect was responsible for the exacerbated cadmium pollution. Therefore, this study may break the stereotypes about the interactions between heavy metal ions and soil minerals. The results suggest that water management (e.g., irrigation) may be prioritized before beginning heavy metal remediation.

10.
Ecol Evol ; 14(2): e11001, 2024 Feb.
Article de Anglais | MEDLINE | ID: mdl-38352203

RÉSUMÉ

Soil microorganisms play vital roles in regulating multiple ecosystem functions. Recent studies have revealed that the rare microbial taxa (with extremely low relative abundances, which are still largely ignored) are also crucial in maintaining the health and biodiversity of the soil and may respond differently to environmental pressure. However, little is known about the soil community structures of abundant and rare taxa and their assembly processes in different soil layers on the Qinghai-Tibet Plateau (QTP). The present study investigated the community structure and assembly processes of soil abundant and rare microbial taxa on the northeastern edge of the QTP. Soil microbial abundance was defined by abundant taxa, whereas rare taxa contributed to soil microbial diversity. The results of null model show that the stochastic process ruled the assembly processes of all sub-communities. Dispersal limitation contributed more to the assembly of abundant microbial taxa in the different soil layers. In contrast, drift played a more critical role in the assembly processes of the rare microbial taxa. In addition, in contrast to previous studies, the abundant taxa played more important roles in co-occurrence networks, most likely because of the heterogeneity of the soil, the sparsity of amplicon sequencing, the sampling strategy, and the limited samples in the present study. The results of this study improve our understanding of soil microbiome assemblies on the QTP and highlight the role of abundant taxa in sustaining the stability of microbial co-occurrence networks in different soil layers.

11.
Nat Commun ; 15(1): 310, 2024 Jan 05.
Article de Anglais | MEDLINE | ID: mdl-38182595

RÉSUMÉ

The increase in intense tropical cyclone (TC) activity across the western North Pacific (WNP) has often been attributed to a warming ocean. However, it is essential to recognize that the tropical WNP region already boasts high temperatures, and a marginal increase in oceanic warmth due to global warming does not exert a significant impact on the potential for TCs to intensify. Here we report that the weakened vertical wind shear is the primary driver behind the escalating trend in TC intensity within the summer monsoon trough of the tropical WNP, while local ocean surface and subsurface thermodynamic factors play a minor role. Through observational diagnoses and numerical simulations, we establish that this weakening of the vertical wind shear is very likely due to the increase in temperature of the Tibetan Plateau. With further warming of the Tibetan Plateau under the Representative Concentration Pathway 4.5 scenario, the projected TCs will likely become stronger.

12.
Zhongguo Zhong Yao Za Zhi ; 48(21): 5779-5789, 2023 Nov.
Article de Chinois | MEDLINE | ID: mdl-38114173

RÉSUMÉ

This study aims to mine the transcription factors that affect the genuineness of Codonopsis pilosula in Shanxi based on the transcriptome data of C. pilosula samples collected from Shanxi and Gansu, and then analyze the gene expression patterns, which will provide a theoretical basis for the molecular assisted breeding of C. pilosula. Gene ontology(GO) functional annotation, conserved motif prediction, and gene expression pattern analysis were performed for the differential transcription factors predicted based on the transcriptome data of C. pilosula from different habitats. A total of 61 differentially expressed genes(DEGs) were screened out from the transcriptome data. Most of the DEGs belonged to AP2/ERF-ERF family, with the conserved motif of [2X]-[LG]-[3X]-T-[3X]-[AARAYDRAA]-[3X]-[RG]-[2X]-A-[2X]-[NFP]. Forty-three of the DEGs showed significantly higher gene expression in C. pilosula samples from Shanxi than in the samples from Gansu, including 11 genes in the AP2/ERF-ERF family, 5 genes in the NAC fa-mily, 1 gene in the bHLH family, and 2 genes in the RWP-RK family, while 18 transcription factors showed higher expression levels in the samples from Gansu. GO annotation predicted that most of the DEGs were enriched in GO terms related to transcriptional binding activity(103), metabolic process(26), and stress response(23). The expression of transcription factor genes, CpNAC92, CpNAC100, CpbHLH128, and CpRAP2-7 was higher in the samples from Shanxi and in the roots of C. pilosula. CpNAC92, CpbHLH128, and CpRAP2-7 responded to the low temperature, temperature difference, and iron stresses, while CpNAC100 only responded to low temperature and iron stresses. The screening and expression analysis of the specific transcription factors CpNAC92, CpNAC100, CpbHLH128, and CpRAP2-7 in C. pilosula in Shanxi laid a theoretical foundation for further research on the mechanism of genuineness formation of C. pilosula.


Sujet(s)
Codonopsis , Codonopsis/génétique , Codonopsis/composition chimique , Facteurs de transcription/génétique , Analyse de profil d'expression de gènes , Transcriptome , Fer
13.
Ecol Evol ; 13(11): e10675, 2023 Nov.
Article de Anglais | MEDLINE | ID: mdl-37928197

RÉSUMÉ

Subsect. Hirculoideae Engl. & Irmsch., belonging to Saxifraga sect. Ciliatae Haw., has high species richness. It can be divided into S. diversifolia, S. pseudohirculus, and S. sinomontana complexes based on morphological characteristics. The species with prominent leaf veins on the posterior leaf edge were placed in the S. diversifolia complex, which is mainly distributed on the eastern and southern margins of the Qinghai-Tibetan Plateau. In this study, 53 samples, representing 15 of the 33 described species in the S. diversifolia complex, were sequenced using the Restriction-site Associated DNA Sequence (RAD-seq) technique. A total of 111,938 high-quality SNP loci were screened to investigate the phylogenetic relationships within the S. diversifolia complex. The result of the neighbor-joining (NJ) tree shows that the S. diversifolia complex is a paraphyletic group. Despite of some inconsistencies as revealed by genetic structural analysis, clustering results of representative species reconstructed by both NJ and principal component analysis analyses support previous biogeographic and morphological evidences. In addition, long-distance gene flow events for 11 taxa were detected in the S. diversifolia complex, respectively from S. implicans 1 to S. implicans 2, S. diversifolia and S. maxionggouensis, and from S. maxionggouensis to S. nigroglandulifera. These findings may improve our comprehension of the phylogeny, classification, and evolution of the S. diversifolia complex.

14.
Int J Biol Sci ; 19(14): 4457-4475, 2023.
Article de Anglais | MEDLINE | ID: mdl-37781038

RÉSUMÉ

Chemotherapy is a standard method in traditional treatment for gastric cancer. It is well known that the anti-tumor effects of chemotherapy are achieved mainly through the direct killing of cancer cells via apoptosis. However, chemotherapy often fails due to drug resistance. Therefore, non-apoptotic cell death induction by ferroptosis has recently been proposed as a new therapeutic modality to ablate cancer. In this study, we determined the role of MKL-1 in ferroptosis. In vitro and in vivo experiments showed that inhibition of MKL-1 expression significantly enhanced cell sensitivity to ferroptosis-inducing agents. It functions by targeting system Xc- to affect the synthesis of GSH in cells. Therefore, we developed an exosome-based therapeutic approach targeting MKL-1, which provides a novel insight into the treatment of gastric cancer.


Sujet(s)
Ferroptose , Tumeurs de l'estomac , Humains , Ferroptose/génétique , Tumeurs de l'estomac/traitement médicamenteux , Tumeurs de l'estomac/génétique , Apoptose/génétique , Glutathion/métabolisme
15.
Chemosphere ; 345: 140448, 2023 Dec.
Article de Anglais | MEDLINE | ID: mdl-37839742

RÉSUMÉ

Heavy metal (HM) pollution, particularly in its ionic form in water bodies, is a chronic issue threatening environmental security and human health. The microalgal-bacterial symbiosis (MABS) system, as the basis of water ecosystems, has the potential to treat HM wastewater in a sustainable manner, with the advantages of environmental friendliness and carbon sequestration. However, the differences between laboratory studies and engineering practices, including the complexity of pollutant compositions and extreme environmental conditions, limit the applications of the MABS system. Additionally, the biomass from the MABS system containing HMs requires further disposal or recycling. This review summarized the recent advances of the MABS system treating HM wastewater, including key mechanisms, influence factors related to HM removal, and the tolerance threshold values of the MABS system to HM toxicity. Furthermore, the challenges and prospects of the MABS system in treating actual HM wastewater are analyzed and discussed, and suggestions for biochar preparation from the MABS biomass containing HMs are provided. This review provides a reference point for the MABS system treating HM wastewater and the corresponding challenges faced by future engineering practices.


Sujet(s)
Métaux lourds , Microalgues , Humains , Eaux usées , Symbiose , Écosystème , Métaux lourds/analyse , Biomasse , Eau
16.
Nanoscale ; 15(32): 13428-13436, 2023 Aug 17.
Article de Anglais | MEDLINE | ID: mdl-37547945

RÉSUMÉ

Polymer composites with good thermal conductivity are gaining more and more attention in the current electronics sector, due to their superior heat management capabilities. However, conventional thermally conductive polymer composites are usually subject to interruptions in heat transfer because of physical damage. The present study prepared mechanical property-enhanced thermally-conductive self-healing composites through compositing a self-healing polyurethane matrix with hydroxylated boron nitride (hyBNNSs). The self-healing polyurethane was obtained by incorporating ligands and cerium(III) triflate [Ce(SO3CF3)3] as the metal center into the polyurethane elastomer. An optimal sample (PUp2C) with high tensile strength (6.8 MPa) and stretchability (1053%), ideal toughness (49.2 MJ m-3), and remarkable healing efficiency (97% healing after 48 h at 35 °C) was obtained. An increase in the content of hyBNNSs from 10% to 30% led to a significant increase in the mechanical performance of hyBNNSs20%/PUp2C, which manifested as the increase in the elongation at break (from 1053% to 1302.5%) and stress (from 6.8 MPa to 16.4 MPa). The XRD results revealed that combining PU with hyBNNSs through coordination bonds could significantly promote the crystallization of PUp2C, which was beneficial to enhancing the mechanical properties of the composites. The through-plane (λ⊥) and the in-plane (λ∥) values of the BNNSs30%/PUp2C composite reached 0.41 and 1.42 W mK-1, respectively, which were 195.2% and 507.1% higher than those of the original PUp2C, respectively.

18.
BMC Cancer ; 23(1): 727, 2023 Aug 05.
Article de Anglais | MEDLINE | ID: mdl-37543576

RÉSUMÉ

BACKGROUND: Low grade glioma (LGG) is considered a heterogeneous tumor with highly variable survival and limited efficacy of immunotherapy. To identify high-risk subsets and apply immunotherapy effectively in LGG, the status and function of immune infiltration in the glioma microenvironment must be explored. METHODS: Four independent glioma cohorts comprising 1,853 patients were enrolled for bioinformatics analysis. We used ConsensusClusterPlus to cluster patients into four different immune subtypes based on immune infiltration. The immune-infiltration signature (IIS) was constructed by LASSO regression analysis. Somatic mutation and copy number variation (CNV) analyses were performed to explore genomic and transcriptomic traits in the high- and low- risk groups. The correlation between response to programmed cell death 1 (PD-1) blockade and the IIS risk score was confirmed in an in vivo glioma model. RESULTS: Patients were clustered into four different immune subtypes based on immune infiltration, and the high immune infiltration subtype was associated with worse survival in LGG. The high immune infiltration subtype had stronger inflammatory response, immune response and immune cell chemotaxis. The IIS, consisting of EMP3, IQGAP2, METTL7B, SLC1A6 and TNFRSF11B, could predict LGG malignant progression, which was validated with internal clinical samples. M2 macrophage infiltration positively correlated with the IIS risk score. The high-risk group had significantly more somatic mutations and CNVs. The IIS risk score was related to immunomodulatory molecules and could predict immunotherapy clinical benefit. In vivo, immunotherapy-sensitive glioma model exhibited higher IIS risk score and more infiltration of immune cells, especially M2 macrophages. The IIS risk score was decreased in an immunotherapy-sensitive glioma model after anti-PD1 immunotherapy. CONCLUSION: Different immune subtypes of LGG had unique immune cell infiltration characteristics, and the high immune infiltration subtype was associated with immunosuppressive signaling pathways. A novel IIS prognostic model based on immune infiltration status was constructed for immunophenotypic classification, risk stratification, prognostication and immunotherapy response prediction in LGG.


Sujet(s)
Variations de nombre de copies de segment d'ADN , Gliome , Humains , Gliome/génétique , Gliome/thérapie , Immunothérapie , Pronostic , Immunomodulation , Microenvironnement tumoral/génétique , Glycoprotéines membranaires , Protéines d'activation de la ras GTPase
19.
Cancer Immunol Res ; 11(10): 1400-1413, 2023 10 04.
Article de Anglais | MEDLINE | ID: mdl-37467346

RÉSUMÉ

Cholesterol is often enriched in tumor microenvironment (TME); however, its impact on disease progression varies in different tissues and cells. Monocytes/macrophages (Mφ) are major components and regulators of the TME and play pivotal roles in tumor progression and therapeutic responses. We aimed to investigate the profile, effects, and regulatory mechanisms of Mφ cholesterol metabolism in the context of human hepatocellular carcinoma (HCC). Here, we found that patients with high serum levels of cholesterol had shorter survival times and lower response rates to anti-PD-1 treatment. However, the cholesterol content in tumor-infiltrating monocytes/Mφ was significantly lower than that in their counterparts in paired nontumor tissues. The expression of the cholesterol efflux transporter, ABCA1, was upregulated in tumor monocytes/Mφ, and ABCA1 upregulation positively associated with decreased cellular cholesterol content and increased serum cholesterol levels. Mechanistically, autocrine cytokines from tumor-treated monocytes increased LXRα and ABCA1 expression, which led to the generation of immature and immunosuppressive Mφ. Although exogenous cholesterol alone had little direct effect on Mφ, it did act synergistically with tumor-derived factors to promote ABCA1 expression in Mφ with more immunosuppressive features. Moreover, high numbers of ABCA1+ Mφ in HCC tumors associated with reduced CD8+ T-cell infiltration and predicted poor clinical outcome for patients. Our results revealed that dysregulated cholesterol homeostasis, due to the collaborative effects of tumors and exogenous cholesterol, drives the generation of immunosuppressive Mφ. The selective modulation of cholesterol metabolism in Mφ may represent a novel strategy for cancer treatment.


Sujet(s)
Carcinome hépatocellulaire , Tumeurs du foie , Humains , Carcinome hépatocellulaire/anatomopathologie , Tumeurs du foie/métabolisme , Macrophages/métabolisme , Monocytes/métabolisme , Cholestérol/métabolisme , Cholestérol/pharmacologie , Microenvironnement tumoral
20.
BMC Musculoskelet Disord ; 24(1): 542, 2023 Jul 01.
Article de Anglais | MEDLINE | ID: mdl-37393235

RÉSUMÉ

BACKGROUND: Spontaneous intramuscular hemorrhage (SIH) is a rare but life-threatening complication of dermatomyositis (DM). The pathogenetic mechanism and management of intramuscular hematoma in these patients remains unclear. Here we discuss a case of recurrent hemorrhage in a patient with cancer-associated DM, and review the relevant literature for timely diagnosis and treatment. CASE PRESENTATION: A 53-year-old male patient presented with rashes, muscle weakness, and dysphagia and was diagnosed with DM. During treatment, he developed SIH of the arm and right psoas major muscle successively. MRI showed extensive edema of the right shoulder girdle muscle and muscle groups of the upper arm. During the second SIH, a CT scan showed new-onset hematoma formation in the right psoas major muscle. The detection of D-dimer, thrombin-antithrombin III complex (TAT), plasmin-α2-plasmininhibitor complex (PIC) and tissue plasminogen activator-inhibitor complex (t-PAIC) indicated predominant hyperfibrinolysis over thrombosis. Blood transfusion and supportive treatment were immediately performed, and the hematoma did not expand. However, his abdominal distension was not relieved after active treatment. Further electronic gastroscopy discovered gastric sinus ulcers, and histopathology of the biopsy confirmed signet-ring cell carcinoma. CONCLUSIONS: Although patients with cancer-associated DM have an increased risk of thrombosis, prophylactic anticoagulation therapy needs deliberate consideration. It is important to monitor the coagulation parameters dynamically during anticoagulation therapy. Especially when the level of D-dimer is high, and it is uncertain whether the patient is in a state of thrombosis or hyperfibrinolysis, the detection of TAT, PIC, t-PAIC can help to determine whether to initiate anticoagulation therapy.


Sujet(s)
Dermatomyosite , Tumeurs , Mâle , Humains , Adulte d'âge moyen , Activateur tissulaire du plasminogène , Dermatomyosite/complications , Hémorragie , Hématome/imagerie diagnostique , Hématome/étiologie , Tumeurs/complications , Tumeurs/imagerie diagnostique , Anticoagulants
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