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1.
CNS Neurosci Ther ; 30(7): e14829, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38961264

RESUMO

AIMS: Paclitaxel (PTX) is extensively utilized in the management of diverse solid tumors, frequently resulting in paclitaxel-induced peripheral neuropathy (PIPN). The present study aimed to investigate sex differences in the behavioral manifestations and underlying pathogenesis of PIPN and search for clinically efficacious interventions. METHODS: Male and female C57BL/6 mice (5-6 weeks and 12 months, weighing 18-30 g) were intraperitoneally (i.p.) administered paclitaxel diluted in saline (NaCl 0.9%) at a dose of 2 mg/kg every other day for a total of 4 injections. Von Frey and hot plate tests were performed before and after administration to confirm the successful establishment of the PIPN model and also to evaluate the pain of PIPN and the analgesic effect of PD-L1. On day 14 after PTX administration, PD-L1 protein (10 ng/pc) was injected into the PIPN via the intrathecal (i.t.) route. To knock down TRPV1 in the spinal cord, adeno-associated virus 9 (AAV9)-Trpv1-RNAi (5 µL, 1 × 1013 vg/mL) was slowly injected via the i.t. route. Four weeks after AAV9 delivery, the downregulation of TRPV1 expression was verified by immunofluorescence staining and Western blotting. The levels of PD-L1, TRPV1 and CGRP were measured via Western blotting, RT-PCR, and immunofluorescence staining. The levels of TNF-α and IL-1ß were measured via RT-PCR. RESULTS: TRPV1 and CGRP protein and mRNA levels were higher in the spinal cords of control female mice than in those of control male mice. PTX-induced nociceptive behaviors in female PIPN mice were greater than those in male PIPN mice, as indicated by increased expression of TRPV1 and CGRP. The analgesic effects of PD-L1 on mechanical hyperalgesia and thermal sensitivity were significantly greater in female mice than in male mice, with calculated relative therapeutic levels increasing by approximately 2.717-fold and 2.303-fold, respectively. PD-L1 and CGRP were partly co-localized with TRPV1 in the dorsal horn of the mouse spinal cord. The analgesic effect of PD-L1 in PIPN mice was observed to be mediated through the downregulation of TRPV1 and CGRP expression following AAV9-mediated spinal cord specific decreased TRPV1 expression. CONCLUSIONS: PTX-induced nociceptive behaviors and the analgesic effect of PD-L1 in PIPN mice were sexually dimorphic, highlighting the significance of incorporating sex as a crucial biological factor in forthcoming mechanistic studies of PIPN and providing insights for potential sex-specific therapeutic approaches.


Assuntos
Antígeno B7-H1 , Peptídeo Relacionado com Gene de Calcitonina , Camundongos Endogâmicos C57BL , Paclitaxel , Doenças do Sistema Nervoso Periférico , Caracteres Sexuais , Canais de Cátion TRPV , Animais , Paclitaxel/toxicidade , Masculino , Feminino , Camundongos , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Canais de Cátion TRPV/metabolismo , Canais de Cátion TRPV/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Antineoplásicos Fitogênicos/toxicidade , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo
2.
Front Oncol ; 14: 1393684, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966070

RESUMO

Background: This study focuses on determining the prognostic and predictive value of the comprehensive prognostic nutrition index (FIDA) in individuals undergoing treatment for Non-Small-Cell Lung Carcinoma (NSCLC). Methods: This retrospective analysis encompassed 474 of NSCLC patients treated from January 2010 through December 2019. Employing the Lasso-COX regression approach, eight blood parameters were identified as significant prognostic indicators. These parameters contributed to the formulation of the comprehensive prognostic nutrition index FIDA. Utilizing X-tile software, the patient cohort was categorized into either a high or low FIDA group based on an established optimal threshold. The cohort was then randomly segmented into a training set and a validation set using SPSS software. Subsequent steps involved conducting univariate and multivariate regression analyze to develop a prognostic nomogram. The effectiveness of this nomogram was evaluated by calculating the AUC. Results: Analysis of survival curves for both the training and validation sets revealed a poorer prognosis in the high FIDA group compared to the low FIDA group. This trend persisted across various subgroups, including gender, age, and smoking history, with a statistical significance (p<0.05). Time-dependent ROC and diagnostic ROC analyses affirmed that FIDA serves as an effective diagnostic and prognostic marker in NSCLC. Moreover, Cox regression multivariate analysis established FIDA as an independent prognostic factor for NSCLC. The prognostic nomogram, integrating FIDA and clinical data, demonstrated substantial prognostic utility and outperformed the traditional TNM staging systemin predicting overall survival (OS). Conclusion: FIDA emerges as a dependable predictor of outcomes for patients with NSCLC. It offers a practical, cost-effective tool for prognostication in regular clinical applications.

3.
Cancer Invest ; 42(6): 527-537, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38965994

RESUMO

Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Humanos , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Neoplasias Retais/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Idoso , Quimioembolização Terapêutica/métodos , Prognóstico , Resultado do Tratamento , Adulto , Quimiorradioterapia/métodos
4.
ACS Nano ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976394

RESUMO

Ceramic aerogel is an appealing fireproof and heat-insulation material, but synchronously improving its mechanical and thermal properties is a challenge. Moreover, the expensive discontinuous processing techniques inhibit the large-scale fabrication of ceramic aerogels. Here, we propose a water-based electrospinning method, based on the hydrolysis and condensation reactions of ceramic precursor salts themselves, for the continuous and rapid (0.025 m3/min) fabrication of ceramic fiber sponge aerogels with dual micronano fiber networks, which show synchronous enhanced fireproof, thermal insulation, and resilience performance. The elastic ceramic micro/nano fiber sponge aerogels contain robust silica-based microfibers as a firm skeleton and alumina-based nanofibers as elastic thermal insulation filler. The sponges have a high porosity of >99.8%, a low mass density (6.21 mg/cm3), a small thermal conductivity (0.022 W/m·K), and a large compression strength (21.15 kPa at 80% strain). The ceramic fiber sponges can effectively prevent the propagation of thermal runaway when a lithium battery experiences catastrophic thermal shock (>1000 °C) in the power battery packs. The proposed strategy is feasible for low-cost and rapid synthesizing ceramic aerogels toward effective battery thermal management.

5.
Shanghai Kou Qiang Yi Xue ; 33(2): 190-194, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-39005098

RESUMO

PURPOSE: To observe the effect of orthodontics combined with restoration on masticatory function in deep overbite patients with severe lower anterior teeth attrition. METHODS: From January 2018 to January 2022, a total of 164 deep overbite patients with severe lower anterior teeth attrition were collected and divided into two groups according to different treatment plans: control group(72 patients, with restoration treatment) and experimental group(92 patients, with orthodontics combined with restoration treatment). The chewing efficiency of the two groups was evaluated, temporomandibular joint dysfunction index (DI), muscle palpation index (PI) and cranio-mandibular index (CMI) were calculated. The satisfaction with facial esthetic, the Chinese version of Oral Health Impact Scale-14(OHIP-14) and the repair satisfaction score were evaluated, the occurrence of adverse events between the two groups was compared. SPSS 23.0 software package was used for statistical analysis. RESULTS: After treatment, the chewing efficiency of the experimental group was significantly improved compared to the control group, while the DI, PI, and CMI were significantly reduced compared to the control group(P<0.05). Compared with the control group, the satisfaction degree with facial esthetic and restoration in the experimental group was significantly higher, while the OHIP-14 score was significantly lower after treatment(P<0.05). The incidence of adverse events in the experimental group was significantly decreased compared with the control group (6.52% vs 25.00%, P<0.05). CONCLUSIONS: Combination of orthodontics and restoration treatment can enhance the effectiveness of restoration treatment for deep overbite with severe lower anterior teeth attrition, improve the mastication function and temporomandibular joint balance,satisfaction and quality of life of patients, as well as reduce the risk of adverse events.


Assuntos
Mastigação , Sobremordida , Humanos , Sobremordida/terapia , Ortodontia/métodos , Ortodontia Corretiva/métodos , Satisfação do Paciente , Transtornos da Articulação Temporomandibular/terapia
6.
Front Nutr ; 11: 1418305, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38993240

RESUMO

Background and objective: Allergic rhinitis (AR) is a common chronic inflammatory disease that significantly impacts the quality of life of patients. However, there is limited research on the relationship between the Dietary Inflammatory Index (DII) and the risk of AR. Our study aimed to assess the association between DII and AR in a sample of adults from North China. Methods: In a case-control study, we selected 166 cases of AR and 166 age- and gender-matched controls. Dietary intake was assessed using a validated food frequency questionnaire. The energy-adjusted DII (E-DII) scores were calculated based on the quantity of diet components with inflammatory or anti-inflammatory potential. We used conditional logistic regression models to examine the association between E-DII and AR. Results: Our findings indicate a positive correlation between E-DII and AR risk. After controlling for confounders, individuals in the highest E-DII tertile exhibited a 4.41-fold increased risk of AR compared to those in the lowest tertile (OR 4.41, 95% CI 2.31-8.41). Additionally, stratified analysis showed that E-DII was positively associated with AR subtype (seasonal vs. perennial), duration (≤6 years vs. >6 years), severity (mild vs. moderate-severe), and onset time (intermittent vs. persistent). Furthermore, individuals in the highest E-DII tertile had higher intake of total fat, SFA, PUFAs, and n-6 PUFAs. Conclusion: In conclusion, we realized that there is a positive association between the E-DII score and AR. The consumption of diets abundant in anti-inflammatory nutrients and low in pro-inflammatory nutrient contents is recommended as a preventative strategy against AR.

7.
Front Neurosci ; 18: 1399653, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38979126

RESUMO

Background: Etomidate can induce myoclonus with an incidence of 50 ~ 85% during anesthesia induction. Dexamethasone, as a long-acting synthetic glucocorticoid, has neuroprotective effects. However, the effects of dexamethasone on the etomidate-induced myoclonus remain uncertain. Methods: Adult male Sprague-Dawley rats were randomly assigned to receive etomidate (1.5 mg/kg) plus dexamethasone (4 mg/kg) (etomidate plus dexamethasone group) or etomidate (1.5 mg/kg) plus the same volume of normal saline (NS) (etomidate plus NS group). The mean behavioral scores, local field potentials and muscular tension were recorded to explore the effects of dexamethasone on etomidate-induced myoclonus. Liquid chromatography coupled with tandem mass spectrometric system (LC-MS/MS), quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting were applied to analyze the levels of glutamate and γ-aminobutyric acid (GABA), the mRNA and protein expression of excitatory amino acid transporters (EAATs), and plasma corticosterone levels at different time points after anesthesia. Results: Compared with the etomidate plus NS treatment, the etomidate plus dexamethasone treatment significantly decreased the mean behavioral score at 1, 3, 4, and 5 min after administration; the peak power spectral density (PSD) (p = 0.0197) in the analysis of ripple waves; and the glutamate level (p = 0.0139) in the neocortex. However, compared with etomidate plus NS, etomidate plus dexamethasone increased the expression of the neocortical proteins of EAAT1 (p = 0.0207) and EAAT2 (p = 0.0022) and aggravated the inhibition of corticosterone at 4 h (p = 0.0019), 5 h (p = 0.0041), and 6 h (p = 0.0009) after administration. Conclusion: Dexamethasone can attenuate the myoclonus, inhibit the glutamate accumulation, and reverse the suppression of EAATs in the neocortex induced by etomidate following myoclonus, while conversely aggravating etomidate-induced adrenal suppression.

8.
Phys Rev E ; 109(6-2): 065212, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39020935

RESUMO

The analytical expression for the conditions of the solid-fluid phase transition, i.e., the melting curve, for two-dimensional (2D) Yukawa systems is derived theoretically from the isomorph theory. To demonstrate that the isomorph theory is applicable to 2D Yukawa systems, molecular dynamical simulations are performed under various conditions. Based on the isomorph theory, the analytical isomorphic curves of 2D Yukawa systems are derived using the local effective power-law exponent of the Yukawa potential. From the obtained analytical isomorphic curves, the melting curve of 2D Yukawa systems is directly determined using only two known melting points. The determined melting curve of 2D Yukawa systems well agrees with the previous obtained melting results using completely different approaches.

9.
Heliyon ; 10(12): e33220, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39021916

RESUMO

Seahorses are increasingly recognized for their nutritional potential, which underscores the necessity for comprehensive biochemical analyses. This study aims to investigate the fatty acid and amino acid compositions of eight seahorse species, including both genders of Hippocampus trimaculatus, Hippocampus kelloggi, Hippocampus abdominalis, and Hippocampus erectus, to evaluate their nutritional value. We employed Gas Chromatography-Mass Spectrometry (GC-MS) and High-Performance Liquid Chromatography (HPLC) to analyze the fatty acid and amino acid profiles of the seahorse species. GC-MS was used to detect 34 fatty acid methyl esters, while HPLC provided detailed amino acid profiles. GC-MS analysis demonstrated high precision with relative standard deviations (RSDs) generally below 2.53 %, satisfactory repeatability (RSDs from 6.55 % to 8.73 %), and stability (RSDs below 2.82 %). Recovery rates for major fatty acids ranged from 98.73 % to 109.12 %. HPLC analysis showed strong separation of amino acid profiles with theoretical plate numbers exceeding 5000. Precision tests yielded RSDs below 1.23 %, with reproducibility and stability tests showing RSDs below 2.73 % and 2.86 %, respectively. Amino acid recovery rates ranged from 97.58 % to 104.66 %. Nutritional analysis revealed significant variations in fatty acid content among the species. Female H. erectus showed higher levels of hexadecanoic acid and saturated fatty acids, while male H. abdominalis had lower concentrations of n-3 full cis 4,7,10,13,16,19-docosahexaenoic acid (DHA). Total lipid yields varied from 3.2491 % to 12.3175 %, with major fatty acids constituting 17.9717 %-74.6962 % of total lipids. In conclusion, this study provides essential insights into the fatty acid and amino acid composition of seahorses, supporting their potential as valuable dietary supplements. The differences between genders in specific fatty acids suggest a nuanced nutritional profile that could be exploited for targeted dietary applications. Further research is needed to explore the seasonal and environmental variations affecting seahorse biochemical composition.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38958649

RESUMO

A novel slightly halophilic, aerobic, and Gram-stain-negative strain, designated as CH-27T, was isolated during a bacterial resource investigation of intertidal sediment collected from Xiaoshi Island in Weihai, PR China. Cells of strain CH-27T were rod-shaped with widths of 0.3-0.6 µm and lengths of 2.0-11.0 µm. Strain CH-27T grew optimally at 37 °C, pH 7.0 and with 2.0 % (w/v) NaCl. Catalase activity was weakly positive and oxidase activity was positive. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CH-27T was most related to Marinihelvus fidelis KCTC 92639T (93.6 %), followed by Wenzhouxiangella marina MCCC 1K00261T (92.0 %). Based on genome comparisons between strain CH-27T and M. fidelis KCTC 92639T, the average amino acid identity was 63.6 % and the percentage of conserved proteins was 48.3 %. The major cellular fatty acid of strain CH-27T (≥10 %) was iso-C15 : 0 and the sole respiratory quinone was quinone-8. The polar lipids were phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, and aminophospholipid. The DNA G+C content was 62.7 mol%. Based on comprehensive analysis of its phylogenetic, physiological, biochemical, and chemotaxonomic characteristics, strain CH-27T represents a novel species in a novel genus, for which the name Elongatibacter sediminis gen. nov., sp.nov. is proposed. The type strain is CH-27T (=MCCC 1H00480T=KCTC 8011T).


Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Sedimentos Geológicos , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Ácidos Graxos/química , Sedimentos Geológicos/microbiologia , China , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Genoma Bacteriano , Fosfolipídeos/química
11.
Acta Pharmacol Sin ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992118

RESUMO

Brain microvascular endothelial cells (BMECs), an important component of the neurovascular unit, can promote angiogenesis and synaptic formation in ischaemic mice after brain parenchyma transplantation. Since the therapeutic efficacy of cell-based therapies depends on the extent of transplanted cell residence in the target tissue and cell migration ability, the delivery route has become a hot research topic. In this study, we investigated the effects of carotid artery transplantation of BMECs on neuronal injury, neurorepair, and neurological dysfunction in rats after cerebral ischaemic attack. Purified passage 1 endothelial cells (P1-BMECs) were prepared from mouse brain tissue. Adult rats were subjected to transient middle cerebral artery occlusion (MCAO) for 30 min. Then, the rats were treated with 5 × 105 P1-BMECs through carotid artery infusion or tail vein injection. We observed that carotid artery transplantation of BMECs produced more potent neuroprotective effects than caudal injection in MCAO rats, including reducing infarct size and alleviating neurological deficits in behavioural tests. Carotid artery-transplanted BMECs displayed a wider distribution in the ischaemic rat brain. Immunostaining for endothelial progenitor cells and the mature endothelial cell markers CD34 and RECA-1 showed that carotid artery transplantation of BMECs significantly increased angiogenesis. Carotid artery transplantation of BMECs significantly increased the number of surviving neurons, decreased the cerebral infarction volume, and alleviated neurological deficits. In addition, we found that carotid artery transplantation of BMECs significantly enhanced ischaemia-induced hippocampal neurogenesis, as measured by doublecortin (DCX) and Ki67 double staining within 2 weeks after ischaemic injury. We conclude that carotid artery transplantation of BMECs can promote cerebral angiogenesis, neurogenesis, and neurological function recovery in adult rats after ischaemic stroke. Our results suggest that carotid injection of BMECs may be a promising new approach for treating acute brain injuries.

12.
Am J Med Sci ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38944203

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is closely related to metabolic syndrome and remains a major global health burden. The increased prevalence of obesity and type 2 diabetes mellitus (T2DM) worldwide has contributed to the rising incidence of NAFLD. It is widely believed that atherosclerotic cardiovascular disease (ASCVD) is associated with NAFLD. In the past decade, the clinical implications of NAFLD have gone beyond liver-related morbidity and mortality, with a majority of patient deaths attributed to malignancy, coronary heart disease (CHD), and other cardiovascular (CVD) complications. To better define fatty liver disease associated with metabolic disorders, experts proposed a new term in 2020 - metabolic dysfunction associated with fatty liver disease (MAFLD). Along with this new designation, updated diagnostic criteria were introduced, resulting in some differentiation between NAFLD and MAFLD patient populations, although there is overlap. The aim of this review is to explore the relationship between MAFLD and ASCVD based on the new definitions and diagnostic criteria, while briefly discussing potential mechanisms underlying cardiovascular disease in patients with MAFLD.

13.
Nat Microbiol ; 9(7): 1686-1699, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38898217

RESUMO

The continuing emergence of invasive fungal pathogens poses an increasing threat to public health. Here, through the China Hospital Invasive Fungal Surveillance Net programme, we identified two independent cases of human infection with a previously undescribed invasive fungal pathogen, Rhodosporidiobolus fluvialis, from a genus in which many species are highly resistant to fluconazole and caspofungin. We demonstrate that R. fluvialis can undergo yeast-to-pseudohyphal transition and that pseudohyphal growth enhances its virulence, revealed by the development of a mouse model. Furthermore, we show that mouse infection or mammalian body temperature induces its mutagenesis, allowing the emergence of hypervirulent mutants favouring pseudohyphal growth. Temperature-induced mutagenesis can also elicit the development of pan-resistance to three of the most commonly used first-line antifungals (fluconazole, caspofungin and amphotericin B) in different Rhodosporidiobolus species. Furthermore, polymyxin B was found to exhibit potent activity against the pan-resistant Rhodosporidiobolus mutants. Collectively, by identifying and characterizing a fungal pathogen in the drug-resistant genus Rhodosporidiobolus, we provide evidence that temperature-dependent mutagenesis can enable the development of pan-drug resistance and hypervirulence in fungi, and support the idea that global warming can promote the evolution of new fungal pathogens.


Assuntos
Antifúngicos , Mutagênese , Animais , Camundongos , Humanos , Virulência/genética , Antifúngicos/farmacologia , China , Temperatura Corporal , Modelos Animais de Doenças , Ascomicetos/genética , Ascomicetos/patogenicidade , Ascomicetos/efeitos dos fármacos , Caspofungina/farmacologia , Testes de Sensibilidade Microbiana , Fluconazol/farmacologia , Micoses/microbiologia , Farmacorresistência Fúngica Múltipla/genética , Farmacorresistência Fúngica/genética
14.
Food Chem ; 455: 139862, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38833866

RESUMO

Laccase mediators possess advantage of oxidizing substrates with high redox potentials, such as aflatoxin B1 (AFB1). High costs of chemically synthesized mediators limit laccase industrial application. In this study, thin stillage extract (TSE), a byproduct of corn-based ethanol fermentation was investigated as the potential natural mediator of laccases. Ferulic acid, p-coumaric acid, and vanillic acid were identified as the predominant phenolic compounds of TSE. With the assistance of 0.05 mM TSE, AFB1 degradation activity of novel laccase Glac1 increased by 17 times. The promoting efficiency of TSE was similar to ferulic acid, but superior to vanillic acid and p-coumaric acid, with 1.2- and 1.3-fold increases, respectively. After Glac1-TSE treatment, two oxidation products were identified. Ames test showed AFB1 degradation products lost mutagenicity. Meanwhile, TSE also showed 1.3-3.0 times promoting effect on laccase degradation activity in cereal flours. Collectively, a safe and highly efficient natural mediator was obtained for aflatoxin detoxification.


Assuntos
Lacase , Zea mays , Lacase/metabolismo , Lacase/química , Zea mays/química , Zea mays/metabolismo , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Aflatoxina B1/química , Aflatoxina B1/metabolismo , Oxirredução , Extratos Vegetais/química , Fermentação , Ácidos Cumáricos/química , Ácidos Cumáricos/metabolismo
15.
Eur J Cancer ; 207: 114147, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38834016

RESUMO

BACKGROUND: We aim to compare the prognostic value of organ-specific dynamics with the sum of the longest diameter (SLD) dynamics in patients with metastatic colorectal cancer (mCRC). METHODS: All datasets are accessible in Project Data Sphere, an open-access platform. The tumor growth inhibition models developed based on organ-level SLD and SLD were used to estimate the organ-specific tumor growth rates (KGs) and SLD KG. The early tumor shrinkage (ETS) from baseline to the first measurement after treatment was also evaluated. The relationship between organ-specific dynamics, SLD dynamics, and survival outcomes (overall survival, OS; progression-free survival, PFS) was quantified using Kaplan-Meier analysis and Cox regression. RESULTS: This study included 3687 patients from 6 phase III mCRC trials. The liver emerged as the most frequent metastatic site (2901, 78.7 %), with variable KGs across different organs in individual patients (liver 0.0243 > lung 0.0202 > lymph node 0.0127 > other 0.0118 [week-1]). Notably, the dynamics for different organs did not equally contribute to predicting survival outcomes. In liver metastasis cases, liver KG proved to be a superior prognostic indicator for OS and surpasses the predictive performance of SLD, (C-index, liver KG 0.610 vs SLD KG 0.606). A similar result can be found for PFS. Moreover, liver ETS also outperforms SLD ETS in predicting survival. Cox regression analysis confirmed liver KG is the most significant variable in survival prediction. CONCLUSIONS: In mCRC patients with liver metastasis, liver dynamics is the primary prognostic indicator for both PFS and OS. In future drug development for mCRC, greater emphasis should be directed towards understanding the dynamics of liver metastasis development.


Assuntos
Neoplasias Colorretais , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/mortalidade , Masculino , Feminino , Prognóstico , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/mortalidade , Pessoa de Meia-Idade , Idoso , Intervalo Livre de Progressão , Ensaios Clínicos Fase III como Assunto
16.
Food Chem Toxicol ; 190: 114776, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38851522

RESUMO

Environmental pollution is one of the risk factors for asthma. Currently, whether micro-plastics could aggravate asthma, is still unclear. In the air, fibrous MPs are the predominant shape. Since fibrous micro-plastics are reported to be detected in the lower respiratory tract and other body parts, the relationship of fibrous MP and asthma, as well as the potential mechanism is not well investigated. In this study, we produced fibrous MPs, whose lengths and widths were in accordance with the natural environment, and further, investigated the potential adverse effect of which on the asthma in a OVA (ovalbumin)-induced mice model, aiming at exploring the true life hazard of MP to the respiratory system. Following nasal exposure to fibrous MPs, the airway inflammation, mucus hypersecretion and fibrosis were aggravated in asthmatic mice. Fibrous MPs exposure also significantly increased the levels of total IgE, and, cardinal Th2 and Th1 pro-inflammatory cytokines participated in the etiopathogenesis of allergic airway inflammation. In addition, MP fibers exposure induced lung epithelial cells apoptosis, disruption of epithelial barrier integrity and activation of NLRP3 related signaling pathways. Moreover, fibrous MPs significantly altered the bacterial composition at the genus level. Compared to the control group, the relative abundance of Escherichia-Shigella and Uncultured were decreased to 4.47% and 0.15% in OVA group, while Blautia and Prevotella were elevated to 4.96% and 2.94%. For the OVA + MPs group, the relative abundance of Blautia and Uncultured were decreased to 2.27% and 0.006%, while Prevotella was increased to 3.05%. Our study highlights the detrimental effect of fibrous MPs on asthmatic population and facilitates an indication of the latent mechanisms of fibrous MPs induced airway pathology.


Assuntos
Asma , Pulmão , Camundongos Endogâmicos BALB C , Microplásticos , Ovalbumina , Animais , Asma/induzido quimicamente , Microplásticos/toxicidade , Camundongos , Pulmão/patologia , Pulmão/efeitos dos fármacos , Feminino , Microbiota , Citocinas/metabolismo
19.
Opt Express ; 32(11): 18562-18571, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38859009

RESUMO

The relative intensity noise (RIN) characteristics of a continuous-wave diamond Raman laser are investigated for the first time. The results reveal the parasitic stimulated Brillouin scattering (SBS) that usually occurred with higher-order spatial modes in the diamond Raman resonator is a pivotal factor impacting the Raman longitudinal modes and deteriorating the RIN level. The diamond Raman laser automatically switches to single-longitudinal-mode operation and the RIN level is significantly decreased in the frequency range of 200 Hz to 1 MHz after the parasitic SBS is effectively suppressed through inserting a spatial aperture or a χ(2) nonlinear crystal into the cavity. Due to the introduction of additional nonlinear loss to the high intensity Raman fluctuations and the non-lasing spontaneous Raman modes, the χ(2) nonlinear crystal enables better performance in the RIN-level reduction compared to the spatial aperture which can only achieve SBS inhibition. The RIN reduction routes are well suited for various crystalline Raman media to achieve high power and low intensity noise laser at different wavelengths.

20.
Opt Express ; 32(8): 14713-14718, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38859408

RESUMO

High power 509 nm continuous-wave (CW) lasers have important applications in science and communication. Here we demonstrate a robust high-power single-frequency 509 nm laser system based on nonlinear phase demodulation technique and single-pass second harmonic generation (SHG) configuration. In experiments, the single-frequency fundamental wave at 1018 nm was linewidth-broadened by an electro-optical modulator and then amplified to 207 W in a ytterbium-doped fiber amplifier. In subsequent single-pass SHG stage, over 20 W CW single-frequency 509 nm laser was generated in a LiB3O5 crystal with a SHG efficiency of 9.7%. To the best of our knowledge, this is the highest reported power for CW single-frequency 509 nm laser, which could be used for advanced underwater optical communication and preparation of cesium Rydberg state.

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