Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 226
Filtrar
1.
Pharmaceuticals (Basel) ; 17(3)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38543149

RESUMO

General anesthetics were first used over 170 years ago; however, the mechanisms of how general anesthetics induce loss of consciousness (LOC) remain unclear. Ciprofol, a novel intravenous anesthetic, has been developed by incorporating cyclopropyl into the chemical structure of propofol. This modification offers the benefits of rapid onset and minimal injection pain. Recent studies have revealed that the glutamatergic neurons of the lateral habenula (LHb) play a crucial role in modulating the LOC induced by propofol and sevoflurane. Nevertheless, the specific involvement of LHb in the anesthetic effects of ciprofol remains uncertain. Here, using targeted recombination in active populations (TRAP) combined with electroencephalogram/electromyography recordings and the righting reflex behavioral test, our study revealed that intravenous infusion of ciprofol for 1 h could lead to the induction of c-Fos expression in the LHb in mice. The combination of TRAP and gene ablation, aimed at selectively ablating ciprofol-activated neurons in the LHb, has been shown to facilitate the emergence of ciprofol anesthesia and decrease the proportion of delta waves during the emergence phase. Chemogenetic inhibition of these neurons produced a comparable effect, whereas chemogenetic activation resulted in the opposite outcome. Chemogenetic activation of ciprofol-activated neurons in the LHb delays the emergence of anesthesia and induces a deep hypnotic state during the emergence phase. Taken together, our findings suggest that LHb ciprofol-activated neurons modulate the state of consciousness and could potentially be targeted to manipulate consciousness during ciprofol anesthesia.

2.
Artigo em Chinês | MEDLINE | ID: mdl-38403419

RESUMO

Objective: Explore the application of Delphi method and analytic hierarchy process to explore the construction of scientific, objective and comprehensive evaluation index system for healthy enterprise construction and promote the construction of healthy enterprises. Methods: In October 2022, through Delphi expert consultation and analytic hierarchy process, the indexes were screened and the weights of the indexes were determined, and the evaluation index system of healthy enterprises was established. Results: The positive coefficients of experts in the two rounds were all 100.00%, the authority coefficient of experts was 0.82, the coefficients of variation of the indexes in the two rounds were all less than 0.30. The coordination coefficients of experts in the first and second rounds were 0.64 and 0.77, respectively (P<0.001) . After two rounds of Delphi method expert consultation, a healthy enterprise evaluation index system including 4 first-level indexes, 14 second-level indexes, and 63 third-level indexes was constructed. Conclusion: The constructed health enterprise evaluation index system is highly scientific and reliable, covering the main factors of healthy enterprise construction, and providing a reliable and quantifiable basis and self-assessment basis for the establishment of healthy enterprises.


Assuntos
Processo de Hierarquia Analítica , Nível de Saúde , Técnica Delphi , China
3.
Zhonghua Zhong Liu Za Zhi ; 45(11): 948-954, 2023 Nov 23.
Artigo em Chinês | MEDLINE | ID: mdl-37968080

RESUMO

Objectives: To find the prognostic factors related to early triple-negative breast cancer to optimize the therapeutic strategies, and explore the influence of programmed cell death ligand-1(PD-L1)expression in early triple-negative breast cancer on its prognosis, so as to provide support for clinical treatment decisions. Methods: Early triple-negative breast cancer patients treated at the National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences during 1st June, 2009 and 31st Oct, 2015 were enrolled in this study. All the clinicopathological data of patients were collected, and the paraffin sections of the surgical specimens were stained with estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2, secreted protein acidic and rich in cysteine (SPARC), androgen receptor, PD-L1 and other antibodies by the immunohistochemical method. Kaplan-Meier survival and Cox regression curves were used for survival analysis of relevant clinical and pathological results and nomogram survival prediction models were established to explore the influence of relevant factors on the prognosis. Results: A total of 205 patients with triple-negative breast cancer were enrolled. Ninety patients (43.9%) were PD-L1 positive. The median follow-up time was 63 months. Thirty-seven patients were relapsed or recurrent and 16 patients were dead. The 5-year disease-free survival (DFS) rate and overall survival (OS) rate were 86.1% (95% CI: 81.4%-90.8%) and 93.6% (95% CI: 91.0%-97.6%), respectively, in the general population. Univariate Cox regression analysis showed that PD-L1 expression and lymph node metastasis were correlated with DFS and OS (P<0.05). In multivariate analysis, PD-L1 expression was an independent influencing factor of DFS, with PD-L1 positive patients possessing a significant survival benefit in DFS (HR=0.31, 95% CI: 0.13-0.73). Lymph node metastasis was an independent influencing factor of OS, and OS was significantly shortened in patients with positive lymph node metastasis (HR=3.24, 95% CI: 1.15-9.17). PD-L1, lymph node metastasis, menopausal status, Ki-67 index and adjuvant chemotherapy regimen were included to establish the 1- and 3-year DFS and OS nomogram prediction models, resulting in C indices of 0.698 and 0.748, respectively. Conclusions: PD-L1 expression is a predictive biomarker of good prognostic factor in triple-negative breast cancer patients. DFS is significantly prolonged in PD-L1 positive patients and OS also shows a prolongation trend. The nomogram prognosis prediction models have reference values for adjuvant chemotherapy in this patient group.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Metástase Linfática , Antígeno B7-H1/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Osteonectina/uso terapêutico , Prognóstico
4.
Zhonghua Wai Ke Za Zhi ; 61(8): 666-674, 2023 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-37400209

RESUMO

Objective: To compare the volumetric changes of cervical disc herniation (CDH) after cervical microendoscopic laminoplasty(CMEL),expansive open-door laminoplasty (EOLP) and conservative treatment. Methods: A retrospective study was conducted involving 101 patients with cervical spondylotic myelopathy(CSM),at the Department of Orthopaedic Surgery,the First Affiliated Hospital of Zhengzhou University from April 2012 to April 2021. The patients included 52 males and 49 females with an age of (54.7±11.8) years(range:25 to 86 years). Among them, 35 patients accepted CMEL treatment,33 patients accepted EOLP treatment,while 33 patients accepted conservative treatment. Volume data of CDH were measured by three-dimensional analysis of the initial and follow-up MRI images. The absorption rate and reprotrusion rate of CDH were calculated. The happening of resorption or reprotrusion was defined when the ratio was greater than 5%. The clinical outcomes and quality of life were evaluated by the Japanese Orthopaedic Association (JOA) score and the neck disability index (NDI).Quantitative data was analyzed by one-way ANOVA with post LSD-t test (multiple comparison) or Kruskal-Wallis test. Categorical data was analyzed by χ2 test. Results: The follow-up time of the CMEL group,EOLP group and the conservative treatment group were (27.6±18.8)months,(21.6±6.9)months and(24.9±16.3)months respectively with no significant difference(P>0.05). Changes of CDH volume in patients:(1) There were 96 CDH of 35 patients in the CMEL group,among which 78 showed absorption. The absorption frequency was 81.3%(78/96) and the absorption rate was ranged 5.9% to 90.9%;9 CDH showed reprotrusion,the reprotrusion frequency was 9.4% (9/96) and the reprotrusion rate was 5.9% to 13.3%;(2) There were 94 CDH of 33 patients in the EOLP group,of which 45 showed absorption. The absorption prevalence was 47.9% (45/94) and the absorption rate was 5.0% to 26.7%;20 CDH showed reprotruded,with the reprotrusion frequency of 21.3% (20/94) and the reprotrusion rate was 5.8% to 28.3%;(3) There were 102 CDH in 33 patients of the conservative group. Among them, 5 showed absorption. The absorption frequency was 4.9% (5/102),and the absorption rate was 7.2% to 14.3%;58 CDH showed reprotruded with the re-protrusion ratio of 56.9% (58/102) and the re-protrusion rate was 5.4% to 174.1%. The absorption ratio and reprotrusion ratio of the CMEL group were statistically different from EOLP group or the conservative group (P<0.01).The absorption ratio and reprotrusion ratio of the EOLP group was different from conservative group (all P<0.01). In terms of clinical outcomes, the excellent/good rate of the JOA score and NDI scores in the CMEL group were different from that of conservative group (all P<0.01) but not from that of the EOLP group(P>0.05). Conclusions: CMEL is an effective method for the treatment of CSM,making CDH easier to resorption compared to the EOLP or conservative treatment,thus making a better decompression effect on the nerves. This study enlightened on a new strategy for the clinical treatment of CSM.


Assuntos
Deslocamento do Disco Intervertebral , Laminoplastia , Doenças da Medula Espinal , Espondilose , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Deslocamento do Disco Intervertebral/cirurgia , Tratamento Conservador , Qualidade de Vida , Resultado do Tratamento , Espondilose/cirurgia , Vértebras Cervicais/cirurgia , Laminoplastia/métodos , Descompressão
5.
J Environ Manage ; 342: 118280, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37276623

RESUMO

Planning multistage implementation plans, or roadmaps, based on the spatial distribution of a best management practice (BMP) scenario is essential for achieving watershed management goals under realistic conditions, such as stepwise investment plans that involve multiple stakeholders, including investors, economic and environmental beneficiaries. The state-of-the-art BMP roadmap optimization method can address this need for optimization but is over-specialized and complex to non-expert stakeholders. This study designed a user-friendly web-based participatory watershed planning system to assist a diverse group of stakeholders in reaching a consensus on optimal roadmaps. The participatory process of stakeholders includes iteratively proposing stepwise investment constraints, submitting roadmap optimization tasks, analyzing spatiotemporal results from multiple perspectives, and selecting preferred roadmaps. The proposed system design separates the participatory process of non-expert stakeholders from the specialized modeling process of constructing simulation-optimization tools for BMP roadmaps, which is done in advance by professional modelers and encapsulated as webservices on the server side. The webservices expose a small set of essential parameters to lower barriers to use. The interactive participatory process is presented to stakeholders through web browsers with an easy-to-use interface. The system design was evaluated by implementing an agricultural watershed planning system for soil erosion reduction and conducting a role-playing experiment involving three groups of stakeholders with different standpoints in proposing investment constraints. The experimental results show that the optimal roadmap sets exhibit progressive improvements across three-round optimizations started by different stakeholders, effectively capturing the varying perspectives of stakeholders and facilitating consensus-building among them. The idea of system design and example implementation can serve as a valuable reference for developing related user-friendly environmental decision support systems.


Assuntos
Agricultura , Internet , Agricultura/métodos , Simulação por Computador
6.
Sensors (Basel) ; 23(11)2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37299892

RESUMO

Semantic segmentation with deep learning networks has become an important approach to the extraction of objects from very high-resolution remote sensing images. Vision Transformer networks have shown significant improvements in performance compared to traditional convolutional neural networks (CNNs) in semantic segmentation. Vision Transformer networks have different architectures to CNNs. Image patches, linear embedding, and multi-head self-attention (MHSA) are several of the main hyperparameters. How we should configure them for the extraction of objects in VHR images and how they affect the accuracy of networks are topics that have not been sufficiently investigated. This article explores the role of vision Transformer networks in the extraction of building footprints from very-high-resolution (VHR) images. Transformer-based models with different hyperparameter values were designed and compared, and their impact on accuracy was analyzed. The results show that smaller image patches and higher-dimension embeddings result in better accuracy. In addition, the Transformer-based network is shown to be scalable and can be trained with general-scale graphics processing units (GPUs) with comparable model sizes and training times to convolutional neural networks while achieving higher accuracy. The study provides valuable insights into the potential of vision Transformer networks in object extraction using VHR images.


Assuntos
Fontes de Energia Elétrica , Semântica , Redes Neurais de Computação , Resolução de Problemas , Telemetria , Processamento de Imagem Assistida por Computador
7.
Stem Cell Reports ; 18(6): 1355-1370, 2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-37172587

RESUMO

Both the canonical Wnt and androgen receptor (AR) signaling pathways are important for prostate organogenesis and homeostasis. How they crosstalk to regulate prostate stem cell behaviors remains unclear. Here, we show in lineage-tracing mouse models that although Wnt is essential for basal stem cell multipotency, ectopic Wnt activity promotes basal cell over-proliferation and squamous phenotypes, which are counteracted by elevated levels of androgen. In prostate basal cell organoids, dihydrotestosterone (DHT) antagonizes R-spondin-stimulated growth in a concentration-dependent manner. DHT down-regulates the expressions of a Wnt reporter and target genes, and RNA sequencing (RNA-seq) analyses identify Wnt signaling as a key altered pathway. Mechanistically, DHT enhances AR and ß-catenin protein binding, and CUT&RUN analyses reveal that ectopic AR sequesters ß-catenin away from its Wnt-related cistrome. Our results suggest that an intermediate level of Wnt activity in prostate basal stem cells, achieved via AR-ß-catenin interaction, is essential for normal prostate homeostasis.


Assuntos
Androgênios , Neoplasias da Próstata , Masculino , Humanos , Camundongos , Animais , Androgênios/farmacologia , Próstata/metabolismo , beta Catenina/metabolismo , Receptores Androgênicos/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Via de Sinalização Wnt
8.
Artigo em Chinês | MEDLINE | ID: mdl-36882277

RESUMO

Objective: To study the correlation between ceramic and chronic obstructive pulmonary disease (COPD), and explore its related risk factors. Methods: In January 2021, five representative ceramic enterprises were selected from Chancheng District, Nanhai District, Gaoming District and Sanshui District of Foshan City. The ceramic workers who came to Chancheng Hospital of Foshan First People's Hospital for physical examination from January to October 2021 were selected as the research objects, and 525 people were included. Conduct questionnaire survey and pulmonary function test. Logistic regresion was performed to analyze the influencing facters of COPD among ceramic workers. Results: The subjects were (38.51±1.25) years old, 328 males and 197 females, and the detection rate of COPD was 9.52% (50/525). The incidence of respiratory symptoms such as dyspnea, chronic cough, wheezing and chest tightness, the detection rates of abnormal lung age, abnormal lung function and COPD in males were higher than those in females (P<0.05). The logistic regression analysis showed that male, age, working years, smoking status and family history of COPD were the risk factors for COPD among ceramic workers (P<0.05) . Conclusion: The ceramic workers are the high risk population of COPD. We should do a good job in health education, and do a regular physical examination to find the changes of lung function in time, and prevent the occurrence of COPD as soon as possible.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Feminino , Humanos , Masculino , Adulto , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Cerâmica , Educação em Saúde , Hospitais , Exame Físico
9.
Clin Psychol Rev ; 101: 102254, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36804184

RESUMO

Patterns of insecure attachment are associated with psychopathology but the mechanisms involved remain poorly understood. Cognitive science proposes that attachment patterns are influenced by the autobiographical memory system and in turn influence its ongoing functioning. Disturbances in autobiographical memory represent cognitive risks for later emotional difficulties. We systemically reviewed 33 studies (in 28 articles) examining the association between attachment patterns and autobiographical episodic memory (AEM) in individuals from the age of 16 (i.e., from young to older adulthood). Attachment patterns were associated with key areas of AEM phenomenology, including intensity and arousal; detail, specificity, and vividness; coherence and fragmentation; and accuracy and latency. These associations appeared to be moderated by contextual and individual factors; mediated by emotional regulation and schema-based processing; linked to mental health outcomes. Attachment patterns may also influence the impact of certain AEM-based manipulations. We conclude by providing a critical discussion and a research agenda for bringing together attachment, memory, and emotion, with a view to promote mechanism-driven treatment innovation in clinical psychology.


Assuntos
Regulação Emocional , Memória Episódica , Adulto , Idoso , Humanos , Emoções , Rememoração Mental/fisiologia
11.
Sci Bull (Beijing) ; 67(3): 328-340, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36546081

RESUMO

Soil spatial information has traditionally been presented as polygon maps at coarse scales. Solving global and local issues, including food security, water regulation, land degradation, and climate change requires higher quality, more consistent and detailed soil information. Accurate prediction of soil variation over large and complex areas with limited samples remains a challenge, which is especially significant for China due to its vast land area which contains the most diverse soil landscapes in the world. Here, we integrated predictive soil mapping paradigm with adaptive depth function fitting, state-of-the-art ensemble machine learning and high-resolution soil-forming environment characterization in a high-performance parallel computing environment to generate 90-m resolution national gridded maps of nine soil properties (pH, organic carbon, nitrogen, phosphorus, potassium, cation exchange capacity, bulk density, coarse fragments, and thickness) at multiple depths across China. This was based on approximately 5000 representative soil profiles collected in a recent national soil survey and a suite of detailed covariates to characterize soil-forming environments. The predictive accuracy ranged from very good to moderate (Model Efficiency Coefficients from 0.71 to 0.36) at 0-5 cm. The predictive accuracy for most soil properties declined with depth. Compared with previous soil maps, we achieved significantly more detailed and accurate predictions which could well represent soil variations across the territory and are a significant contribution to the GlobalSoilMap.net project. The relative importance of soil-forming factors in the predictions varied by specific soil property and depth, suggesting the complexity and non-stationarity of comprehensive multi-factor interactions in the process of soil development.


Assuntos
Solo , Solo/química , China
12.
Artigo em Inglês | MEDLINE | ID: mdl-36361167

RESUMO

Classroom silence is a negative form of classroom performance that is particularly prominent in the Chinese learner population. Existing research has mainly explored the silence phenomenon among Chinese university students in two types of learning contexts: overseas university classrooms and foreign language classrooms at local universities, without focusing on the Chinese undergraduates' reticence in courses mediated by native language at domestic universities. However, the last type is the most common habitat for Chinese university students' learning in higher education. Therefore, a sample of Chinese undergraduates majoring in education (n = 394) was recruited to determine the mechanisms of silence formation in professional classrooms. This study was based on grounded theory and in-depth interviews, and the recorded material was processed using NVivo 12. After a series of steps including open coding, axial coding, selective coding, and theoretical saturation testing, the core feature of the phenomenon of silence in professional classrooms of Chinese university students majoring in education was found to be the separation of students' cognition and speaking practice. Then, a theoretical model of the formation and development of the phenomenon of classroom silence in professional classrooms of these undergraduates was constructed. The study showed that these university students had professional perceptions of classroom silence and displayed strong opposition to it, but they continued to maintain silent classroom behavior under the combined influence of individual characteristics, classroom experience, and learning adjustment. Following this, implications for existing research and suggestions for future practice are discussed.


Assuntos
Cognição , Estudantes , Humanos , Universidades , Teoria Fundamentada , China
13.
Mil Med Res ; 9(1): 58, 2022 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-36229865

RESUMO

BACKGROUND: Abnormal myocardial Nav1.5 expression and function cause lethal ventricular arrhythmias during myocardial ischemia-reperfusion (I/R). Protein inhibitor of activated STAT Y (PIASy)-mediated caveolin-3 (Cav-3) SUMO modification affects Cav-3 binding to the voltage-gated sodium channel 1.5 (Nav1.5). PIASy activity is increased after myocardial I/R, but it is unclear whether this is attributable to plasma membrane Nav1.5 downregulation and ventricular arrhythmias. METHODS: Using recombinant adeno-associated virus subtype 9 (AAV9), rat cardiac PIASy was silenced using intraventricular injection of PIASy short hairpin RNA (shRNA). After two weeks, rat hearts were subjected to I/R and electrocardiography was performed to assess malignant arrhythmias. Tissues from peri-infarct areas of the left ventricle were collected for molecular biological measurements. RESULTS: PIASy was upregulated by I/R (P < 0.01), with increased SUMO2/3 modification of Cav-3 and reduced membrane Nav1.5 density (P < 0.01). AAV9-PIASy shRNA intraventricular injection into the rat heart downregulated PIASy after I/R, at both mRNA and protein levels (P < 0.05 vs. Scramble-shRNA + I/R group), decreased SUMO-modified Cav-3 levels, enhanced Cav-3 binding to Nav1.5, and prevented I/R-induced decrease of Nav1.5 and Cav-3 co-localization in the intercalated disc and lateral membrane. PIASy silencing in rat hearts reduced I/R-induced fatal arrhythmias, which was reflected by a modest decrease in the duration of ventricular fibrillation (VF; P < 0.05 vs. Scramble-shRNA + I/R group) and a significantly reduced arrhythmia score (P < 0.01 vs. Scramble-shRNA + I/R group). The anti-arrhythmic effects of PIASy silencing were also evidenced by decreased episodes of ventricular tachycardia (VT), sustained VT and VF, especially at the time 5-10 min after ischemia (P < 0.05 vs. Scramble-shRNA + IR group). Using in vitro human embryonic kidney 293 T (HEK293T) cells and isolated adult rat cardiomyocyte models exposed to hypoxia/reoxygenation (H/R), we confirmed that increased PIASy promoted Cav-3 modification by SUMO2/3 and Nav1.5/Cav-3 dissociation after H/R. Mutation of SUMO consensus lysine sites in Cav-3 (K38R or K144R) altered the membrane expression levels of Nav1.5 and Cav-3 before and after H/R in HEK293T cells. CONCLUSIONS: I/R-induced cardiac PIASy activation increased Cav-3 SUMOylation by SUMO2/3 and dysregulated Nav1.5-related ventricular arrhythmias. Cardiac-targeted PIASy silencing mediated Cav-3 deSUMOylation and partially prevented I/R-induced Nav1.5 downregulation in the plasma membrane of cardiomyocytes, and subsequent ventricular arrhythmias in rats. PIASy was identified as a potential therapeutic target for life-threatening arrhythmias in patients with ischemic heart diseases.


Assuntos
Antiarrítmicos , Caveolina 3 , Proteínas de Ligação a Poli-ADP-Ribose/genética , Proteínas Inibidoras de STAT Ativados/genética , Animais , Arritmias Cardíacas/genética , Caveolina 3/genética , Caveolina 3/metabolismo , Regulação para Baixo , Inativação Gênica , Células HEK293 , Humanos , Isquemia/complicações , Lisina/genética , Lisina/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , RNA Mensageiro , RNA Interferente Pequeno , Ratos , Reperfusão/efeitos adversos
14.
Ann Oncol ; 33(12): 1269-1283, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36089135

RESUMO

BACKGROUND: Targeted therapies have transformed clinical management of advanced biliary tract cancer (BTC). Cell-free DNA (cfDNA) analysis is an attractive approach for cancer genomic profiling that overcomes many limitations of traditional tissue-based analysis. We examined cfDNA as a tool to inform clinical management of patients with advanced BTC and generate novel insights into BTC tumor biology. PATIENTS AND METHODS: We analyzed next-generation sequencing data of 2068 cfDNA samples from 1671 patients with advanced BTC generated with Guardant360. We carried out clinical annotation on a multi-institutional subset (n = 225) to assess intra-patient cfDNA-tumor concordance and the association of cfDNA variant allele fraction (VAF) with clinical outcomes. RESULTS: Genetic alterations were detected in cfDNA in 84% of patients, with targetable alterations detected in 44% of patients. Fibroblast growth factor receptor 2 (FGFR2) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, and BRAF V600E were clonal in the majority of cases, affirming these targetable alterations as early driver events in BTC. Concordance between cfDNA and tissue for mutation detection was high for IDH1 mutations (87%) and BRAF V600E (100%), and low for FGFR2 fusions (18%). cfDNA analysis uncovered novel putative mechanisms of resistance to targeted therapies, including mutation of the cysteine residue (FGFR2 C492F) to which covalent FGFR inhibitors bind. High pre-treatment cfDNA VAF was associated with poor prognosis and shorter response to chemotherapy and targeted therapy. Finally, we report the frequency of promising targets in advanced BTC currently under investigation in other advanced solid tumors, including KRAS G12C (1.0%), KRAS G12D (5.1%), PIK3CA mutations (6.8%), and ERBB2 amplifications (4.9%). CONCLUSIONS: These findings from the largest and most comprehensive study to date of cfDNA from patients with advanced BTC highlight the utility of cfDNA analysis in current management of this disease. Characterization of oncogenic drivers and mechanisms of therapeutic resistance in this study will inform drug development efforts to reduce mortality for patients with BTC.


Assuntos
Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Ácidos Nucleicos Livres , Humanos , Ácidos Nucleicos Livres/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias dos Ductos Biliares/genética , Sequenciamento de Nucleotídeos em Larga Escala , Mutação , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/genética , Neoplasias do Sistema Biliar/patologia
15.
Zhonghua Nei Ke Za Zhi ; 61(9): 1023-1030, 2022 Sep 01.
Artigo em Chinês | MEDLINE | ID: mdl-36008295

RESUMO

Objective: To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT). Methods: A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results: A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment. Conclusion: ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.


Assuntos
Carcinoma de Células Pequenas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Histiocitoma Fibroso Maligno , Melanoma , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Masculino
16.
Zhonghua Liu Xing Bing Xue Za Zhi ; 43(8): 1321-1325, 2022 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-35981997

RESUMO

Objective: To evaluate the typing and clinical application effect based on clustered regularly interspaced short palindromic repeats (CRISPRs), serotype, and Multilocus Sequence Typing (MLST). Methods: The spacers, serotype and sequence type (ST) were obtained with CRISPRsFinder, SeroTypeFinder and MLST. PCR was used to amplify the CRISPRs, and the spacers were used to predict serotype and ST, then comparing with the serotype and ST. Results: We defined the I-E CRISPR/Cas as CT-Ⅰ, I-F CRISPR/Cas as CT-Ⅱ, and only CRISPR3-4 as CT-Ⅲ. We designated each unique arrangement spacer profile as a unique CRISPRs type. A total of 79 CT types, 76 serotypes, and 66 STs were identified. The CRISPRs typing was the most discriminating, with the Simpson index of 0.936, having the highest correlation with serology with the adjusted Rand index of 0.908. The CRISPRs type could divide the same serotype (ST) into two subtypes [O157∶H7(ST11), O104∶H4(ST678), and O26∶H11(ST21)]. The detection rates of CRISPR1, CRISPR2, CRISPR3, CRISPR4, and CRISPR3-4 were 81.1%, 94.5%, 1.4%, 1.4%, and 4.6%, with the accuracy rate of 95.0% and 100.0% according to the spacers to forecast O157∶H7 (ST11) and ST131. Conclusion: Based on the CRISPRs spacer, this method can be used as an essential molecular typing for E.coli, as it presents a good typing and clinical application effect.


Assuntos
Infecções por Escherichia coli , Escherichia coli , Escherichia coli/genética , Humanos , Tipagem de Sequências Multilocus
17.
Heliyon ; 8(6): e09795, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35785229

RESUMO

Existing local models based on multiple environmental variables clustering (LM-MEVC) treat the influences of environmental factors on leaf phosphorus concentration (LPC) of rubber trees (Hevea brasiliensis) equally when grouping samples. In fact, the effects that environmental factors assert on LPC are different. So, environmental factors need to be treated differently so that the different effects can be taken into consideration when dividing samples into clusters or groups. According to this basic idea, a local model based on weighted environmental variables clustering (LM-WEVC) was developed. This approach consists of four steps. Firstly, the most important environmental variables that influence LPC were selected. Then, the weights of the selected environmental variables were determined. In the following, the selected environmental variables were weighted and used as clustering variables to group samples. Finally, within each cluster or group of samples, an estimation model was established. In order to verify its effectiveness in predicting LPC of rubber trees, the proposed method was applied to a case study in Hainan Island, China. Rubber tree (cultivar CATAS-7-33-97) leaf samples were collected from three different sampling periods. Spectral reflectance of the collected leaf samples was measured using an ASD spectroradiometer, FieldSpec 3. Leaf samples collected from the three different sampling periods were used separately to test LM-WEVC. Coefficient of determination (R2), root mean squared error (RMSE), and ratio of prediction deviation (RPD) were employed as evaluation criterion. Performance of LM-WEVC was compared with that of the existing LM-MEVC. Results indicated that for the three sampling periods, the prediction accuracies of LM-WEVC were always higher than those of LM-MEVC. The values of R2 and RPD for LM-WEVC were increased by 8.15%-36.68%, and by 11.33%-59.40% respectively, while values of RMSE were reduced by 9.09%-37.5%, compared with those for LM-MEVC. These results demonstrate that LM-WEVC was effective in estimating LPC of rubber trees, and also confirmed our hypothesis that environmental factors unequally influenced LPC of rubber trees.

18.
Food Chem ; 397: 133744, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-35878556

RESUMO

The authentication of geographical origin of food is important using stable isotope analysis. However, the isotopic databank is still short of comprehensive. The isoscapes model based on environmental similarity is used for the first time to predict the geospatial distribution of δ13C, δ2H and δ18O in Chinese rice in 2017 and 2018. 794 rice samples in 2017 were used to build isoscapes model. Independent verification shows that the predicted isotope distribution from this new approach is of high accuracy, with a root mean square error (RMSE) of 0.51 ‰, 7.09 ‰ and 2.06 ‰ for δ13C, δ2H and δ18O values for 2017, respectively. Our results indicate that it is possible to predict the spatial distribution of stable isotopes in rice using an isoscapes model based on environmental similarity. This novel strategy can enrich and complement a stable isotope reference database for rice origin identification at regional scale.


Assuntos
Oryza , Isótopos de Carbono/análise , China , Geografia , Modelos Teóricos , Isótopos de Nitrogênio/análise , Isótopos de Oxigênio/análise
19.
Front Mol Biosci ; 9: 898871, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35865005

RESUMO

It has long been postulated that the inflammatory environment favors cell proliferation, and is conducive to diseases such as cancer. In the prostate gland, clinical data implicate important roles of prostatitis in the progression of both benign prostatic hyperplasia (BPH) and prostate cancer (PCa). However, their causal relationships have not been firmly established yet due to unresolved molecular and cellular mechanisms. By accurately mimicking human disease, vertebrate animals provide essential in vivo models to address this question. Here, we review the vertebrate prostatitis models that have been developed and discuss how they may reveal possible mechanisms by which prostate inflammation promotes BPH and PCa. Recent studies, particularly those involving genetically engineered mouse models (GEMMs), suggest that such mechanisms are multifaceted, which include epithelium barrier disruption, DNA damage and cell proliferation induced by paracrine signals, and expansion of potential cells of origin for cancer. Future research using rodent prostatitis models should aim to distinguish the etiologies of BPH and PCa, and facilitate the development of novel clinical approaches for prostatic disease prevention.

20.
Sci Total Environ ; 837: 155708, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35523329

RESUMO

The spatial distribution of microplastics and the factors influencing their distribution in lakes are important aspects of plastics pollution studies. This study investigated the impacts of lake underwater topography on the spatial distribution of microplastics in Dianchi Lake in China. Data on spatial distribution of microplastics were obtained by pump sampling, microscopic examination, and polymer identification. Parameters of underwater topography were extracted from an isobaths map of Dianchi Lake. The relationships between underwater topography and the abundance of microplastics were analyzed. The results showed that for the northern part of the lake, water depth, slope gradient, relief, roughness and surface curvature have significant relationships with the spatial distribution of microplastics. In the southern part, only roughness showed a significant relationship. The roughness is the only important factor which impacts the microplastics distribution in both parts of the lake and the whole lake. These differences between the northern part and the southern part of the lake are related to the stronger circular currents in the southern part of the lake. These results showed that the impacts of underwater topography manifest themselves well when lake currents are weak, and these impacts are reduced or muted when lake currents are strong. Our research results provide a good reference for understanding distribution and migration principle of microplastics in lakes.


Assuntos
Lagos , Poluentes Químicos da Água , China , Monitoramento Ambiental/métodos , Sedimentos Geológicos , Microplásticos , Plásticos , Poluentes Químicos da Água/análise
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA