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1.
Research (Wash D C) ; 7: 0399, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39015204

RESUMO

With the development of artificial intelligence and breakthroughs in deep learning, large-scale foundation models (FMs), such as generative pre-trained transformer (GPT), Sora, etc., have achieved remarkable results in many fields including natural language processing and computer vision. The application of FMs in autonomous driving holds considerable promise. For example, they can contribute to enhancing scene understanding and reasoning. By pre-training on rich linguistic and visual data, FMs can understand and interpret various elements in a driving scene, and provide cognitive reasoning to give linguistic and action instructions for driving decisions and planning. Furthermore, FMs can augment data based on the understanding of driving scenarios to provide feasible scenes of those rare occurrences in the long tail distribution that are unlikely to be encountered during routine driving and data collection. The enhancement can subsequently lead to improvement in the accuracy and reliability of autonomous driving systems. Another testament to the potential of FMs' applications lies in world models, exemplified by the DREAMER series, which showcases the ability to comprehend physical laws and dynamics. Learning from massive data under the paradigm of self-supervised learning, world models can generate unseen yet plausible driving environments, facilitating the enhancement in the prediction of road users' behaviors and the off-line training of driving strategies. In this paper, we synthesize the applications and future trends of FMs in autonomous driving. By utilizing the powerful capabilities of FMs, we strive to tackle the potential issues stemming from the long-tail distribution in autonomous driving, consequently advancing overall safety in this domain.

2.
J Colloid Interface Sci ; 675: 761-771, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38996705

RESUMO

Among the various non-precious metal catalysts that drive hydrogen evolution reactions (HERs) and dye-sensitized solar cells (DSSCs), transition metal selenides (TMSs) stand out due to their unique electronic properties and tunable morphology. Herein, the multicomponent selenide CuSe-Co3Se4@VSe2 was successfully synthesized by doping with metal element vanadium and selenization on the copper-cobalt carbonate hydroxide (CuCo-CH) template. CuSe-Co3Se4@VSe2 exhibited the dandelion-like cluster structure composed of hollow nanotubes doped with VSe2 nanoparticles. Due to the unique structure and the synergistic effect of various elements, CuSe-Co3Se4@VSe2 showed excellent alkaline HER and DSSC performances. The DSSC based on CuSe-Co3Se4@VSe2 exhibited an impressive power conversion efficiency (PCE) of 9.64 %, which was much higher than that of Pt (8.39 %). Besides, it possessed a low HER overpotential of 76 mV@10 mA cm-2 and a small Tafel slope of 88.9 mV dec-1 in 1.0 M KOH.

3.
Am J Transl Res ; 16(6): 2411-2422, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006260

RESUMO

BACKGROUND: The estrogen receptor (ER) serves as a pivotal indicator for assessing endocrine therapy efficacy and breast cancer prognosis. Invasive biopsy is a conventional approach for appraising ER expression levels, but it bears disadvantages due to tumor heterogeneity. To address the issue, a deep learning model leveraging mammography images was developed in this study for accurate evaluation of ER status in patients with breast cancer. OBJECTIVES: To predict the ER status in breast cancer patients with a newly developed deep learning model leveraging mammography images. MATERIALS AND METHODS: Datasets comprising preoperative mammography images, ER expression levels, and clinical data spanning from October 2016 to October 2021 were retrospectively collected from 358 patients diagnosed with invasive ductal carcinoma. Following collection, these datasets were divided into a training dataset (n = 257) and a testing dataset (n = 101). Subsequently, a deep learning prediction model, referred to as IP-SE-DResNet model, was developed utilizing two deep residual networks along with the Squeeze-and-Excitation attention mechanism. This model was tailored to forecast the ER status in breast cancer patients utilizing mammography images from both craniocaudal view and mediolateral oblique view. Performance measurements including prediction accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curves (AUCs) were employed to assess the effectiveness of the model. RESULTS: In the training dataset, the AUCs for the IP-SE-DResNet model utilizing mammography images from the craniocaudal view, mediolateral oblique view, and the combined images from both views, were 0.849 (95% CIs: 0.809-0.868), 0.858 (95% CIs: 0.813-0.872), and 0.895 (95% CIs: 0.866-0.913), respectively. Correspondingly, the AUCs for these three image categories in the testing dataset were 0.835 (95% CIs: 0.790-0.887), 0.746 (95% CIs: 0.793-0.889), and 0.886 (95% CIs: 0.809-0.934), respectively. A comprehensive comparison between performance measurements underscored a substantial enhancement achieved by the proposed IP-SE-DResNet model in contrast to a traditional radiomics model employing the naive Bayesian classifier. For the latter, the AUCs stood at only 0.614 (95% CIs: 0.594-0.638) in the training dataset and 0.613 (95% CIs: 0.587-0.654) in the testing dataset, both utilizing a combination of mammography images from the craniocaudal and mediolateral oblique views. CONCLUSIONS: The proposed IP-SE-DResNet model presents a potent and non-invasive approach for predicting ER status in breast cancer patients, potentially enhancing the efficiency and diagnostic precision of radiologists.

4.
Int J Med Sci ; 21(9): 1681-1688, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006850

RESUMO

Hypertension affects a large number of individuals globally and is a common cause of nephropathy, stroke, ischaemic heart disease and other vascular diseases. While many anti-hypertensive medications are used safely and effectively in clinic practice, controlling hypertensive complications solely by reducing blood pressure (BP) can be challenging. α-Mangostin, a xanthone molecule extracted from the pericarp of Garcinia mangostana L., has shown various beneficial effects such as anti-tumor, anti-hyperuricemia, and anti-inflammatory properties. However, the effects of α-Mangostin on hypertension remain unknown. In this study, we observed that α-Mangostin significantly decreased systolic and diastolic blood pressure in spontaneously hypertensive rats (SHR), possibly through the down-regulation of angiotensin II (Ang II). We also identified early markers of hypertensive nephropathy, including urinary N-acetyl-ß-D-glucosaminidase (NAG) and ß2-microglobulin (ß2-MG), which were reduced by α-Mangostin treatment. Mechanistic studies suggested that α-Mangostin may inhibit renal tubular epithelial-to-mesenchymal transformation (EMT) by down-regulating the TGF-ß signaling pathway, thus potentially offering a new therapeutic approach for hypertension and hypertensive nephropathy.


Assuntos
Angiotensina II , Pressão Sanguínea , Transição Epitelial-Mesenquimal , Hipertensão , Ratos Endogâmicos SHR , Xantonas , Animais , Xantonas/farmacologia , Xantonas/uso terapêutico , Ratos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertensão/patologia , Fibrose/tratamento farmacológico , Masculino , Linhagem Celular , Garcinia mangostana/química , Transdução de Sinais/efeitos dos fármacos , Hipertensão Renal/tratamento farmacológico , Hipertensão Renal/patologia , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Nefrite
5.
BJUI Compass ; 5(7): 691-698, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39022664

RESUMO

Background: Understanding sex-specific factors contributing to advanced-stage diagnosis can guide interventions to reduce sex inequality in patients with urological cancers. Method: We used linked primary care and cancer registry data to examine associations between symptoms and advanced-stage in 1151 bladder cancer and 440 renal cancer patients diagnosed between January 2012 and December 2015 in England. We performed logistic regression, adjusting for sex, age, deprivation and routes to diagnosis, including interaction terms between symptoms and sex and symptoms and age. Results: Female sex (OR vs. men 1.89 [1.28-2.79]; p = 0.001) and patients presenting with urinary tract infections (OR 2.22 [1.34-3.69]) and abdominal symptoms (OR 2.19 [1.30-3.70]) were associated with increased odds of advanced-stage bladder cancer (vs. haematuria, p = 0.016 for both). Women with haematuria and men with abdominal symptoms (compared with the opposite sex with the same presenting symptom) were more likely to have advanced-stage bladder cancer. Neither sex nor symptom associations were observed for renal cancer. Conclusion: Non-haematuria symptoms are associated with higher risk of advanced-stage bladder cancer. Greater risk of advanced-stage bladder cancer in women may reflect biological differences in haematuria onset and sex differences during diagnostic process. Identifying higher risk women with haematuria may reduce sex inequalities in bladder cancer outcomes.

6.
Dent J (Basel) ; 12(6)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38920864

RESUMO

OBJECTIVE: implementing appropriate pharmacological and non-pharmacological interventions to alleviate pain related to routine dental procedures in paediatric patients could enhance children's ability to manage dental care. The aim of this review was to investigate the effectiveness of and provide recommendations for interventions that can be used to reduce intra-operative and post-operative pain associated with routine paediatric dental procedures. METHODS: A systematic review of randomised controlled clinical trials (RCT) was conducted. Multiple electronic databases were systematically searched. The Cochrane risk-of-bias tool for RCTs was used to evaluate the quality of the included studies. A meta-analysis was performed to determine the effectiveness of the interventions using the Cohen's d standardised mean differences (SMD) and 95% confidence intervals (CIs) for continuous outcomes. The GRADE tool was used to assess the certainty of evidence to make recommendations. RESULTS: The review included forty-five RCTs comprising 3093 children. Thirty-seven RCTs were included in the meta-analysis, which showed the effectiveness of behavioural interventions (SMD = -0.50, 95% CI -0.83 to -0.18), mechanoreceptor and thermal receptor stimulation (SMD = -1.38, 95% CI -2.02 to -0.73) for intra-operative pain, and pre-emptive oral analgesics (SMD = -0.77, 95% CI -1.21 to -0.33) for reducing post-operative pain in children receiving routine dental care. CONCLUSION: The GRADE results for these interventions were strong recommendation (IB) for their use, based on moderate evidence and their benefits far outweighing the harm, and they can be delivered readily with minimal training to reduce the pain experience of paediatric patients.

7.
Environ Monit Assess ; 196(7): 638, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38902529

RESUMO

Urbanization inevitably interfered with the supply and demand of ecosystem services (ESs), which has a crucial impact on the ESs balance. Scientific exploration and clarification of the coupling and decoupling relationship between them can effectively reveal the disturbance of urbanization to the ecosystem, which can help to reasonably manage and protect the ecosystem. Previous studies have paid more attention to the coupling relationship but less attention to the decoupling relationship. This study comprehensively reflected urbanization from the three aspects of construction land, population, and economy and used the evaluation matrix to measure ESs. On this basis, coupling and decoupling analyses were taken to fully clarify the complex relationship between urbanization and ESs balance in China, so as to provide a reference for the formulation of relevant policies. Coupling aspect, the coupling degrees between the proportion of construction land (CLP) and ESs balance index (ESBI) were higher only in the central and eastern plains. The coupling degrees between population density (PD) and ESBI, economic density (ED) and ESBI, and land development index (LDI) and ESBI were only lower in the central and eastern plains than in other regions. Decoupling aspect, strong, weak negative, weak, and strong negative decoupling were the main decoupling types between urbanization and ESs balance in China. Among them, the proportion of the strong decoupling type is much higher than other types, which proves the opposite relationship between the two. Weak decoupling can not only promote economic growth and social development but also protect the ecological environment and biodiversity, which is a type of sustainable development and an ideal state that urbanization should pursue. The results can provide scientific guidance for the formulation of differentiated ecosystem management policies.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Monitoramento Ambiental , Urbanização , China
8.
Cell Metab ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38897198

RESUMO

Immune checkpoint blockade has led to breakthroughs in the treatment of advanced gastric cancer. However, the prominent heterogeneity in gastric cancer, notably the heterogeneity of the tumor microenvironment, highlights the idea that the antitumor response is a reflection of multifactorial interactions. Through transcriptomic analysis and dynamic plasma sample analysis, we identified a metabolic "face-off" mechanism within the tumor microenvironment, as shown by the dual prognostic significance of nicotinamide metabolism. Specifically, macrophages and fibroblasts expressing the rate-limiting enzymes nicotinamide phosphoribosyltransferase and nicotinamide N-methyltransferase, respectively, regulate the nicotinamide/1-methylnicotinamide ratio and CD8+ T cell function. Mechanistically, nicotinamide N-methyltransferase is transcriptionally activated by the NOTCH pathway transcription factor RBP-J and is further inhibited by macrophage-derived extracellular vesicles containing nicotinamide phosphoribosyltransferase via the SIRT1/NICD axis. Manipulating nicotinamide metabolism through autologous injection of extracellular vesicles restored CD8+ T cell cytotoxicity and the anti-PD-1 response in gastric cancer.

9.
RSC Adv ; 14(27): 19550-19559, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38895524

RESUMO

Monoclonal antibodies (mAbs) are pivotal therapeutic agents for various diseases, and effective treatment hinges on attaining a specific threshold concentration of mAbs in patients. With the rising adoption of combination therapy involving multiple mAbs, there arises a clinical demand for multiplexing assays capable of measuring the concentrations of these mAbs. However, minimizing the complexity of serum samples while achieving rapid and accurate quantification is difficult. In this work, we introduced a novel method termed nano-surface and molecular orientation limited (nSMOL) proteolysis for the fragment of antigen binding (Fab) region-selective proteolysis of co-administered trastuzumab and pertuzumab based on the pore size difference between the protease nanoparticles (∼200 nm) and the resin-captured antibody (∼100 nm). The hydrolyzed peptide fragments were then quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this process, the digestion time is shortened, and the produced digestive peptides are greatly reduced, thereby minimizing sample complexity and increasing detection accuracy. Assay linearity was confirmed within the ranges of 0.200-200 µg mL-1 for trastuzumab and 0.300-200 µg mL-1 for pertuzumab. The intra- and inter-day precision was within 9.52% and 8.32%, except for 12.5% and 10.8% for the lower limit of quantitation, and the accuracy (bias%) was within 6.3%. Additionally, other validation parameters were evaluated, and all the results met the acceptance criteria of the guiding principles. Our method demonstrated accuracy and selectivity for the simultaneous determination of trastuzumab and pertuzumab in clinical samples, addressing the limitation of ligand binding assays incapable of simultaneously quantifying mAbs targeting the same receptor. This proposed assay provides a promising technical approach for realizing clinical individualized precise treatment, especially for co-administered mAbs.

10.
Polymers (Basel) ; 16(11)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38891516

RESUMO

Poly(dimethylsiloxane) (PDMS) coatings are considered to be environmentally friendly antifouling coatings. However, the presence of hydrophobic surfaces can enhance the adhesion rate of proteins, bacteria and microalgae, posing a challenge for biofouling removal. In this study, hydrophilic polymer chains were synthesised from methyl methacrylate (MMA), Poly(ethylene glycol) methyl ether methacrylate (PEG-MA) and 3-(trimethoxysilyl) propyl methacrylate (TPMA). The crosslinking reaction between TPMA and PDMS results in the formation of a silicone-based amphiphilic co-network with surface reconstruction properties. The hydrophilic and hydrophobic domains are covalently bonded by condensation reactions, while the hydrophilic polymers migrate under water to induce surface reconstruction and form hydrogen bonds with water molecules to form a dense hydrated layer. This design effectively mitigates the adhesion of proteins, bacteria, algae and other marine organisms to the coating. The antifouling performance of the coatings was evaluated by assessing their adhesion rates to proteins (BSA-FITC), bacteria (B. subtilis and P. ruthenica) and algae (P. tricornutum). The results show that the amphiphilic co-network coating (e.g., P-AM-15) exhibits excellent antifouling properties against protein, bacterial and microalgal fouling. Furthermore, an overall assessment of its antifouling performance and stability was conducted in the East China Sea from 16 May to 12 September 2023, which showed that this silicon-based amphiphilic co-network coating remained intact with almost no marine organisms adhering to it. This study provides a novel approach for the development of high-performance silicone-based antifouling coatings.

12.
J Clin Periodontol ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802320

RESUMO

AIM: This prospective cohort study investigated the association between periodontal diseases (PDs) and all-cause and cause-specific mortality. MATERIALS AND METHODS: We utilized adult participants recruited from six National Health and Nutrition Examination Survey cycles (1999-2014) and linked mortality data from the National Death Index up to December 2019. Baseline clinical periodontal examinations were performed by trained and calibrated examiners. All-cause and cause-specific mortality was modelled through multivariable Cox proportional hazards and Fine-Gray models to account for competing risks. All models were adjusted for demographic and lifestyle variables, clinical measurements and comorbidities. RESULTS: Overall, 15,030 participants were included, with a median length of follow-up of 9 years. Risk of all-cause mortality was 22% greater in people with PD than the control group (adjusted hazard ratio [HR]: 1.22, 95% confidence interval [CI]: 1.12-1.31). Risks of mortality by cardiovascular diseases (CVD), respiratory disease and diabetes were highest in participants with severe PD (CVD-sub-distribution HR [SHR]: 1.38, 95% CI: 1.16-1.64; respiratory-SHR: 1.62, 95% CI: 1.07-2.45; diabetes-SHR: 1.68, 95% CI: 1.12-2.53). CONCLUSIONS: Severe PD is associated with all-cause and cause-specific mortality among US adults after multivariable adjustment.

13.
Front Immunol ; 15: 1369849, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38779681

RESUMO

Background: Stomolophus meleagris envenomation causes severe cutaneous symptoms known as jellyfish dermatitis. The potential molecule mechanisms and treatment efficiency of dermatitis remain elusive because of the complicated venom components. The biological activity and molecular regulation mechanism of Troxerutin (TRX) was firstly examined as a potential treatment for jellyfish dermatitis. Methods: We examined the inhibit effects of the TRX on tentacle extract (TE) obtained from S. meleagris in vivo and in vitro using the mice paw swelling models and corresponding assays for Enzyme-Linked Immunosorbent Assay (ELISA) Analysis, cell counting kit-8 assay, flow cytometry, respectively. The mechanism of TRX on HaCaT cells probed the altered activity of relevant signaling pathways by RNA sequencing and verified by RT-qPCR, Western blot to further confirm protective effects of TRX against the inflammation and oxidative damage caused by TE. Results: TE significantly induced the mice paw skin toxicity and accumulation of inflammatory cytokines and reactive oxygen species in vivo and vitro. Moreover, a robust increase in the phosphorylation of mitogen-activated protein kinase (MAPKs) and nuclear factor-kappa B (NF-κB) signaling pathways was observed. While, the acute cutaneous inflammation and oxidative stress induced by TE were significantly ameliorated by TRX treatment. Notablly, TRX suppressed the phosphorylation of MAPK and NF-κB by initiating the nuclear factor erythroid 2-related factor 2 signaling pathway, which result in decreasing inflammatory cytokine release. Conclusion: TRX inhibits the major signaling pathway responsible for inducing inflammatory and oxidative damage of jellyfish dermatitis, offering a novel therapy in clinical applications.


Assuntos
Dermatite , Hidroxietilrutosídeo , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Cifozoários , Transdução de Sinais , Animais , Estresse Oxidativo/efeitos dos fármacos , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Dermatite/tratamento farmacológico , Dermatite/metabolismo , Dermatite/etiologia , Humanos , Hidroxietilrutosídeo/análogos & derivados , Hidroxietilrutosídeo/farmacologia , Hidroxietilrutosídeo/uso terapêutico , Venenos de Cnidários/farmacologia , Heme Oxigenase-1/metabolismo , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Citocinas/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Células HaCaT , Espécies Reativas de Oxigênio/metabolismo , Proteínas de Membrana
14.
Clin Kidney J ; 17(5): sfae098, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38737345

RESUMO

Background: Chronic kidney disease (CKD) is a major global health problem and its early identification would allow timely intervention to reduce complications. We performed a systematic review and meta-analysis of multivariable prediction models derived and/or validated in community-based electronic health records (EHRs) for the prediction of incident CKD in the community. Methods: Ovid Medline and Ovid Embase were searched for records from 1947 to 31 January 2024. Measures of discrimination were extracted and pooled by Bayesian meta-analysis, with heterogeneity assessed through a 95% prediction interval (PI). Risk of bias was assessed using Prediction model Risk Of Bias ASsessment Tool (PROBAST) and certainty in effect estimates by Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Results: Seven studies met inclusion criteria, describing 12 prediction models, with two eligible for meta-analysis including 2 173 202 patients. The Chronic Kidney Disease Prognosis Consortium (CKD-PC) (summary c-statistic 0.847; 95% CI 0.827-0.867; 95% PI 0.780-0.905) and SCreening for Occult REnal Disease (SCORED) (summary c-statistic 0.811; 95% CI 0.691-0.926; 95% PI 0.514-0.992) models had good model discrimination performance. Risk of bias was high in 64% of models, and driven by the analysis domain. No model met eligibility for meta-analysis if studies at high risk of bias were excluded, and certainty of effect estimates was 'low'. No clinical utility analyses or clinical impact studies were found for any of the models. Conclusions: Models derived and/or externally validated for prediction of incident CKD in community-based EHRs demonstrate good prediction performance, but assessment of clinical usefulness is limited by high risk of bias, low certainty of evidence and a lack of impact studies.

15.
Front Pharmacol ; 15: 1378872, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38756382

RESUMO

Daptomycin is gaining prominence for the treatment of methicillin-resistant Staphylococcus aureus infections. However, the dosage selection for daptomycin in critically ill patients remains uncertain, especially in Chinese patients. This study aimed to establish the population pharmacokinetics of daptomycin in critically ill patients, optimize clinical administration plans, and recommend appropriate dosage for critically ill patients in China. The study included 64 critically ill patients. Blood samples were collected at the designated times. The blood daptomycin concentration was determined using validated liquid chromatography-tandem mass spectrometry. A nonlinear mixed-effects model was applied for the population pharmacokinetic analysis and Monte Carlo simulations of daptomycin. The results showed a two-compartment population pharmacokinetic model of daptomycin in critically ill adult Han Chinese patients. Monte Carlo simulations revealed that a daily dose of 400 mg of daptomycin was insufficient for the majority of critically ill adult patients to achieve the anti-infective target. For critically ill adult patients with normal renal function (creatinine clearance rate >90 mL/min), the probability of achieving the target only reached 90% when the daily dose was increased to 700 mg. For patients undergoing continuous renal replacement therapy (CRRT), 24 h administration of 500 mg met the pharmacodynamic goals and did not exceed the safety threshold in most patients. Therefore, considering its efficacy and safety, intravenous daptomycin doses are best scaled according to creatinine clearance, and an increased dose is recommended for critically ill patients with hyperrenalism. For patients receiving CRRT, medication is recommended at 24 h intervals.

16.
Int J Clin Pharmacol Ther ; 62(7): 339-344, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38606856

RESUMO

High-dose tigecycline is gradually being introduced for the treatment of serious infectious diseases due to the increasing difficulty in treating pan-resistant bacterial infections. However, the safety of high-dose tigecycline is controversial. We report the case of a 76-year-old female patient with cerebral hemorrhage who received high-dose tigecycline (100 mg q12h) with other drugs for ventilator-associated pneumonia. 25 days after admission, she developed acute liver failure, mainly manifested by abnormally high bilirubin, coagulation dysfunction, and gastrointestinal hemorrhage with hemorrhagic shock. According to the updated Roussel Uclaf causality assessment method, the patient's acute liver injury was most likely caused by tigecycline.


Assuntos
Antibacterianos , Falência Hepática Aguda , Tigeciclina , Humanos , Feminino , Idoso , Tigeciclina/administração & dosagem , Tigeciclina/efeitos adversos , Falência Hepática Aguda/induzido quimicamente , Antibacterianos/efeitos adversos , Antibacterianos/administração & dosagem , Minociclina/efeitos adversos , Minociclina/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico
17.
J Mol Neurosci ; 74(2): 36, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38568285

RESUMO

After ischemic stroke, microRNAs (miRNAs) participate in various processes, including immune responses, inflammation, and angiogenesis. Diabetes is a key factor increasing the risk of ischemic stroke; however, the regulatory pattern of miRNAs at different stages of diabetic stroke remains unclear. This study comprehensively analyzed the miRNA expression profiles in diabetic mice at 1, 3, and 7 days post-reperfusion following the middle cerebral artery occlusion (MCAO). We identified differentially expressed (DE) miRNAs in diabetic stroke and found significant dysregulation of some novel miRNAs (novel_mir310, novel_mir89, and novel_mir396) post-stroke. These DEmiRNAs were involved in apoptosis and the formation of tight junctions. Finally, we identified three groups of time-dependent DE miRNAs (miR-6240, miR-135b-3p, and miR-672-5p). These have the potential to serve as biomarkers of diabetic stroke. These findings provide a new perspective for future research, emphasizing the dynamic changes in miRNA expression after diabetic stroke and offering potential candidates as biomarkers for future clinical applications.


Assuntos
Diabetes Mellitus Experimental , AVC Isquêmico , MicroRNAs , Acidente Vascular Cerebral , Animais , Camundongos , Diabetes Mellitus Experimental/genética , Regulação da Expressão Gênica de Plantas , MicroRNAs/genética , Plantas Geneticamente Modificadas , Acidente Vascular Cerebral/genética , Biomarcadores
19.
FEBS J ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38661680

RESUMO

Immune checkpoint inhibitors provide a definite survival benefit for patients with driver-negative advanced non-small cell lung cancer (NSCLC), but predictors of efficacy are still lacking. There may be a relationship between immune inflammatory state and tumor immune response. We explored the relationship of serum neutrophil extracellular traps (NETs) with infiltrating cells in the tumor tissues of patients with NSCLC as well as their relationship with the therapeutic efficacy of programmed cell death protein 1 (PD-1) inhibitors. Serum myeloperoxidase (MPO)-double-stranded DNA (dsDNA) was detected as a marker of NET serum concentration. T cells were detected by immunohistochemical staining, and neutrophils were counted by MPO immunofluorescence staining. Of the 31 patients with NSCLC, a longer progression-free survival after PD-1 inhibitor treatment was associated with higher levels of CD3+ T cells, a lower neutrophil : CD3+-T-cell ratio (NEU/CD3+) and lower neutrophil : CD8+-T-cell ratio (NEU/CD8+) in tumor tissues. Patients with higher serum NETs were more likely to develop progressive disease after treatment (P = 0.003) and to have immune-related adverse events (IrAEs) as well as higher NEU/CD3+ and NEU/CD8+. The combined model of serum NETs, CD8+ T cells, and tumor proportion score (TPS) significantly improved the prediction of PD-1 inhibitor efficacy [P = 0.033; area under the curve (AUC) = 0.881]. Our results indicate that serum NETs are effective predictors of PD-1 inhibitor response and reflect the tissue neutrophil-to-lymphocyte ratio and IrAE levels. The combined model of serum NETs, CD8+ T cells, and TPS is a powerful tool for predicting the efficacy of PD-1 inhibitor treatment in patients with NSCLC.

20.
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