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1.
Cancers (Basel) ; 16(4)2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38398195

RESUMO

PURPOSE: To develop and internally validate a novel prediction score to predict the occurrence of arterial-esophageal fistula (AEF) in esophageal cancer bleeding. METHODS: This retrospective cohort study enrolled patients with esophageal cancer bleeding in the emergency department. The primary outcome was the diagnosis of AEF. The patients were randomly divided into a derivation group and a validation group. In the derivation stage, a predictive model was developed using logistic regression analysis. Subsequently, internal validation of the model was conducted in the validation cohort during the validation stage to assess its discrimination ability. RESULTS: A total of 257 patients were enrolled in this study. All participants were randomized to a derivation cohort (n = 155) and a validation cohort (n = 102). AEF occurred in 22 patients (14.2%) in the derivation group and 14 patients (13.7%) in the validation group. A predictive model (HEARTS-Score) comprising five variables (hematemesis, active bleeding, serum creatinine level >1.2 mg/dL, prothrombin time >13 s, and previous stent implantation) was established. The HEARTS-Score demonstrated a high discriminative ability in both the derivation and validation cohorts, with c-statistics of 0.90 (95% CI 0.82-0.98) and 0.82 (95% CI 0.72-0.92), respectively. CONCLUSIONS: By employing this novel prediction score, clinicians can make more objective risk assessments, optimizing diagnostic strategies and tailoring treatment approaches.

2.
J Am Heart Assoc ; 13(3): e031662, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38240326

RESUMO

BACKGROUND: Public access defibrillation (PAD) programs have been implemented globally over the past decade. Although PAD can substantially increase the survival of cardiac arrest, PAD use remains low. This study aimed to evaluate whether drawing upon the successful experiences of dispatcher-assisted cardiopulmonary resuscitation programs would increase the use of PAD in dispatcher-assisted PAD programs. METHODS AND RESULTS: This study using a before-and-after design was conducted in Taoyuan City using a local out-of-hospital cardiac arrest registry system and data of dispatcher performance derived from audio recordings. The primary outcomes were the rate of bystander PAD use, sustained return of spontaneous circulation, survival to discharge, and favorable neurological outcomes. The secondary outcomes were the performance of dispatchers in terms of PAD instruction and dispatcher-assisted cardiopulmonary resuscitation administration, the time interval indicators of dispatcher-assisted cardiopulmonary resuscitation. A total of 1159 patients were included and divided into 2 groups: the before-run-in group (502 patients) and the after-run-in group (657 patients). No significant difference was observed between the 2 groups in terms of baseline characteristics. The rate of PAD use in the after-run-in group significantly increased from 5.0% to 8.7% (P=0.015). The rate of favorable neurological outcomes increased from 4.4% to 5.9%, which was not a statistically significant difference. Compared with the before-run-in group, the rate of successful automated external defibrillator acquisition was 13.5% in the after-run-in group (P<0.001). CONCLUSIONS: Implementing a dispatcher-assisted PAD protocol in a municipality setting significantly increased bystander PAD use without affecting dispatcher performance in out-of-hospital cardiac arrest recognition, cardiopulmonary resuscitation instruction, or dispatcher-assisted cardiopulmonary resuscitation time indicators.


Assuntos
Reanimação Cardiopulmonar , Serviços Médicos de Emergência , Parada Cardíaca Extra-Hospitalar , Humanos , Parada Cardíaca Extra-Hospitalar/diagnóstico , Parada Cardíaca Extra-Hospitalar/terapia , Reanimação Cardiopulmonar/métodos , Sistema de Registros , Serviços Médicos de Emergência/métodos
3.
J Gastrointest Oncol ; 14(5): 2048-2063, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37969820

RESUMO

Background: Traditional clinical characteristics have certain limitations in evaluating cancer prognosis. The radiomics features provide information on tumor morphology, tissue texture, and hemodynamics, which can accurately reflect personalized predictions. This study investigated the clinical value of radiomics features on contrast-enhanced computed tomography (CT) images in predicting prognosis and postoperative chemotherapy benefits for patients with gastric cancer (GC). Methods: For this study, 171 GC patients who underwent radical gastrectomy and pathology confirmation of the malignancy at the First Affiliated Hospital of Wenzhou Medical University were retrospectively enrolled. The general information, pathological characteristics, and postoperative chemotherapy information were collected. Patients were also monitored through telephone interviews or outpatient treatment. GC patients were randomly divided into the developing cohort (n=120) and validation cohort (n=51). The intra-tumor areas of interest inside the tumors were delineated, and 1,218 radiomics features were extracted. The optimal radiomics risk score (RRS) was constructed using 8 machine learning algorithms and 29 algorithm combinations. Furthermore, a radiomics nomogram that included clinicopathological characteristics was constructed and validated through univariate and multivariate Cox analyses. Results: Eleven prognosis-related features were selected, and an RRS was constructed. Kaplan-Meier curve analysis showed that the RRS had a high prognostic ability in the developing and validation cohorts (log-rank P<0.01). The RRS was higher in patients with a larger tumor size (≥3 cm), higher Charlson score (≥2), and higher clinical stage (Stages III and IV) (all P<0.001). Furthermore, GC patients with a higher RRS significantly benefited from postoperative chemotherapy. The results of univariate and multivariate Cox regression analyses demonstrated that the RRS was an independent risk factor for overall survival (OS) and disease-free survival (DFS) (P<0.001). A visual nomogram was established based on the significant factors in multivariate Cox analysis (P<0.05). The C-index was 0.835 (0.793-0.877) for OS and 0.733 (0.677-0.789) for DFS in the developing cohort. The calibration curve also showed that the nomogram had good agreement. Conclusions: A nomogram that combines the RRS and clinicopathological characteristics could serve as a novel noninvasive preoperative prediction model with the potential to accurately predict the prognosis and chemotherapy benefits of GC patients.

4.
J Gastrointest Oncol ; 14(5): 2134-2145, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37969837

RESUMO

Background: Elderly people and patients with colorectal cancer (CRC) are both at high risk of malnutrition. Therefore, it is of great significance to explore suitable malnutrition screening and diagnostic indicators for elderly patients with CRC. Recently, the Global Leadership Initiative on Malnutrition (GLIM) proposed new diagnostic criteria for malnutrition. The aim of this article was to evaluate the diagnostic value of GLIM criteria for malnutrition in elderly colorectal patients. We explored the relationship between GLIM-malnutrition, post-operative complications and the long-term prognosis of elderly colorectal patients. Methods: Elderly patients (aged ≥65 years) who underwent CRC surgery from January 2015 to December 2018 were included. Malnutrition was diagnosed based on the GLIM criteria. The relationships between GLIM-malnutrition and clinical characteristics were analyzed by t-tests, Mann-Whitney U tests, and chi-squared tests. The relationships between GLIM-malnutrition and post-operative complications were analyzed by chi-squared tests, and logistic regression analyses. The relationships between GLIM-malnutrition and the long-term prognosis were analyzed by Kaplan-Meier analyses and logistic and Cox regression analyses. Results: A total of 385 elderly patients were included in this study, and 118 patients (30.65%) were diagnosed with malnutrition according to the GLIM criteria. GLIM-malnutrition was significantly associated with older age, lower body mass index (BMI), lower grip strength, tumor location, higher Nutrition Risk Screening 2002 (NRS-2002), and lower levels of albumin and hemoglobin. GLIM-malnutrition was an independent risk factor [odds ratio (OR): 1.753, 95% confidence interval (CI): 1.100-2.795, P=0.018] for post-operative complications. Cox regression analysis showed that GLIM-malnutrition was an independent risk factor for overall survival in elderly patients with CRC. Conclusions: The GLIM criteria are feasible diagnostic criteria for malnutrition of elderly patients with CRC. GLIM-malnutrition is significantly associated with post-operative complications and overall survival in elderly patients with CRC.

5.
Cancer Biol Ther ; 24(1): 2274123, 2023 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-37955635

RESUMO

Molecular residual disease (MRD), detected by circulating tumor DNA (ctDNA) can be involved in the entire process of solid tumor management, including recurrence prediction, efficacy evaluation, and risk stratification. Currently, the detection technologies are divided into two main categories, as follows: tumor-agnostic and tumor informed. Tumor-informed assay obtains mutation information by sequencing tumor tissue samples before blood MRD monitoring, followed by formulation of a personalized MRD panel. Tumor-agnostic assays are carried out using a fixed panel without the mutation information from primary tumor tissue. The choice of testing strategy may depend on the level of evidence from ongoing randomized clinical trials, investigator preference, cost-effectiveness, patient economics, and availability of tumor tissue. The review describes the difference between tumor informed and tumor agnostic detection. In addition, the clinical application of ctDNA MRD in solid tumors was introduced, with emphasis on lung cancer, colorectal cancer, Urinary system cancer, and breast cancer.


Assuntos
Neoplasias da Mama , DNA Tumoral Circulante , Neoplasias Pulmonares , Humanos , Feminino , DNA de Neoplasias/genética , DNA Tumoral Circulante/genética , Bioensaio , Compostos Radiofarmacêuticos
6.
Cell Death Dis ; 14(2): 124, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36792578

RESUMO

Abnormal expression and remodeling of cytoskeletal regulatory proteins are important mechanisms for tumor development and chemotherapy resistance. This study systematically analyzed the relationship between differential expression of cytoskeleton genes and prognosis in gastric cancer (GC). We found the Arf GTP-activating protein ASAP1 plays a key role in cytoskeletal remodeling and prognosis in GC patients. Here we analyzed the expression level of ASAP1 in tissue microarrays carrying 564 GC tissues by immunohistochemistry. The results showed that ASAP1 expression was upregulated in GC cells and can be served as a predictor of poor prognosis. Moreover, ASAP1 promoted the proliferation, migration, and invasion of GC cells both in vitro and in vivo. We also demonstrated that ASAP1 inhibited the ubiquitin-mediated degradation of IQGAP1 and thus enhanced the activity of CDC42. The activated CDC42 upregulated the EGFR-MAPK pathway, thereby promoting the resistance to chemotherapy in GC. Taken together, our results revealed a novel mechanism by which ASAP1 acts in the progression and chemotherapy resistance in GC. This may provide an additional treatment option for patients with GC.


Assuntos
Neoplasias Gástricas , Humanos , Proteínas Adaptadoras de Transdução de Sinal , Linhagem Celular Tumoral , Movimento Celular/genética , Proteínas do Citoesqueleto , Citoesqueleto , Proteínas Ativadoras de ras GTPase/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética
7.
Semin Cancer Biol ; 83: 303-318, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-33207266

RESUMO

Pancreatic cancer is one of the most common causes of cancer death in the world due to the lack of early symptoms, metastasis occurrence and chemoresistance. Therefore, early diagnosis by detection of biomarkers, blockade of metastasis, and overcoming chemoresistance are the effective strategies to improve the survival of pancreatic cancer patients. Accumulating evidence has revealed that long noncoding RNA (lncRNA) and circular RNAs (circRNAs) play essential roles in modulating chemosensitivity in pancreatic cancer. In this review article, we will summarize the role of lncRNAs in drug resistance of pancreatic cancer cells, including HOTTIP, HOTAIR, PVT1, linc-ROR, GAS5, UCA1, DYNC2H1-4, MEG3, TUG1, HOST2, HCP5, SLC7A11-AS1 and CASC2. We also highlight the function of circRNAs, such as circHIPK3 and circ_0000284, in regulation of drug sensitivity of pancreatic cancer cells. Moreover, we describe a number of compounds, including curcumin, genistein, resveratrol, quercetin, and salinomycin, which may modulate the expression of lncRNAs and enhance chemosensitivity in pancreatic cancers. Therefore, targeting specific lncRNAs and cicrRNAs could contribute to reverse chemoresistance of pancreatic cancer cells. We hope this review might stimulate the studies of lncRNAs and cicrRNAs, and develop the new therapeutic strategy via modulating these noncoding RNAs to promote chemosensitivity of pancreatic cancer cells.


Assuntos
Neoplasias Pancreáticas , RNA Longo não Codificante , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , RNA Circular/genética , RNA Longo não Codificante/genética , Neoplasias Pancreáticas
8.
Cell Death Dis ; 12(9): 842, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504059

RESUMO

The 5-methylcytosine (m5C) RNA methyltransferase NSUN2 is involved in the regulation of cell proliferation and metastasis formation and is upregulated in multiple cancers. However, the biological significance of NSUN2 in gastric cancer (GC) and the modification of NSUN2 itself have not been fully investigated. Here, we analyzed the expression level of NSUN2 in tissue microarrays containing 403 GC tissues by immunohistochemistry. NSUN2 was upregulated in GC, and that it was a predictor of poor prognosis. NSUN2 promotes the proliferation, migration, and invasion of GC cells in vitro. We also demonstrated that small ubiquitin-like modifier (SUMO)-2/3 interacts directly with NSUN2 by stabilizing it and mediating its nuclear transport. This facilitates the carcinogenic activity of NSUN2. Furthermore, m5C bisulfite sequencing (Bis-seq) in NSUN2-deficient GC cells showed that m5C-methylated genes are involved in multiple cancer-related signaling pathways. PIK3R1 and PCYT1A may be the target genes that participate in GC progression. Our findings revealed a novel mechanism by which NSUN2 functions in GC progression. This may provide new treatment options for GC patients.


Assuntos
5-Metilcitosina/metabolismo , Progressão da Doença , Metiltransferases/metabolismo , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Ubiquitinas/metabolismo , Idoso , Sequência de Aminoácidos , Sequência de Bases , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Núcleo Celular/metabolismo , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Metilação , Metiltransferases/química , Pessoa de Meia-Idade , Modelos Biológicos , Mutação/genética , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , Estabilidade Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Frações Subcelulares/metabolismo , Sumoilação
9.
Sci Rep ; 11(1): 9858, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33972647

RESUMO

Early recognition and rapid initiation of high-quality cardiopulmonary resuscitation (CPR) are key to maximising chances of achieving successful return of spontaneous circulation in patients with out-of-hospital cardiac arrests (OHCAs), as well as improving patient outcomes both inside and outside hospital. Mechanical chest compression devices such as the LUCAS-2 have been developed to assist rescuers in providing consistent, high-quality compressions, even during transportation. However, providing uninterrupted and effective compressions with LUCAS-2 during transportation down stairwells and in tight spaces in a non-supine position is relatively impossible. In this study, we proposed adaptations to the LUCAS-2 to allow its use during transportation down stairwells and examined its effectiveness in providing high-quality CPR to simulated OHCA patients. 20 volunteer emergency medical technicians were randomised into 10 pairs, each undergoing 2 simulation runs per experimental arm (LUCAS-2 versus control) with a loaded Resusci Anne First Aid full body manikin weighing 60 kg. Quality of CPR compressions performed was measured using the CPRmeter placed on the sternum of the manikin. The respective times taken for each phase of the simulation protocol were recorded. Fisher's exact tests were used to analyse categorical variables and median test to analyse continuous variables. The LUCAS-2 group required a longer time (~ 35 s) to prepare the patient prior to transport (p < 0.0001) and arrive at the ambulance (p < 0.0001) compared to the control group. The CPR quality in terms of depth and rate for the overall resuscitation period did not differ significantly between the LUCAS-2 group and control group, though there was a reduction in both parameters when evaluating the device's automated compressions during transport. Nevertheless, the application of the LUCAS-2 device yielded a significantly higher chest compression fraction of 0.76 (p < 0.0001). Our novel adaptations to the LUCAS-2 device allow for uninterrupted compressions in patients being transported down stairwells, thus yielding better chest compression fractions for the overall resuscitation period. Whether potentially improved post-OHCA survival rates may be achieved requires confirmation in a real-world scenario study.


Assuntos
Reanimação Cardiopulmonar/instrumentação , Parada Cardíaca Extra-Hospitalar/terapia , Treinamento por Simulação/métodos , Transporte de Pacientes/métodos , Auxiliares de Emergência , Feminino , Humanos , Masculino , Manequins , Ombro , Macas (Leitos) , Resultado do Tratamento
10.
Front Oncol ; 11: 614925, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33959494

RESUMO

Human cytomegalovirus (HCMV) is an oncogenic virus associated with tumorigenesis. Our previous study revealed that the HCMV US31 gene interacted with NF-κB2 and mediated inflammation through macrophages. However, there are few reports on the role of US31 in gastric cancer (GC). The aim of this study was to investigate the expression of the US31 gene in GC tissue and assess its role in the occurrence and development of GC. US31 expression in 573 cancer tissues was analyzed using immunohistochemistry. Results showed that US31 was significantly associated with tumor size (P = 0.005) and distant metastasis (P < 0.001). Higher US31 expression indicated better overall survival in GC patients. Overexpression of US31 significantly inhibited the proliferation, migration, and invasion of GC cells in vitro (P < 0.05). Furthermore, expression levels of CD4, CD66b, and CD166 were positively correlated with US31, suggesting that it was involved in regulating the tumor immune microenvironment of GC. RNA sequencing, along with quantitative real-time polymerase chain reaction, confirmed that the expression of US31 promoted immune activation and secretion of inflammatory cytokines. Overall, US31 inhibited the malignant phenotype and regulated tumor immune cell infiltration in GC; these results suggest that US31 could be a potential prognostic factor for GC and may open the door for a new immunotherapy strategy.

11.
Pharmacol Ther ; 226: 107869, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33895187

RESUMO

Pancreatic cancer is one of the malignant tumors with poor prognosis. The molecular mechanisms of pancreatic oncogenesis and malignant progression are not fully elucidated. Several key signaling pathways, such as Notch, Wnt and hedgehog pathways, are important to drive pancreatic carcinogenesis. Recently, noncoding RNAs, especially circular RNAs (circRNAs), have been characterized to participate into pancreatic cancer development. Therefore, in this review article, we describe the association between circRNAs and pancreatic cancer prognosis. Moreover, we discuss how circRNAs are involved in regulation of cellular processes in pancreatic cancer, including proliferation, apoptosis, cell cycle, migration, invasion, EMT, metastasis, angiogenesis, drug resistance and immune escape. Furthermore, we mention that several compounds could regulate the expression of circRNAs, indicating that targeting circRNAs by compounds might be helpful for treating pancreatic cancer patients.


Assuntos
Neoplasias Pancreáticas , RNA Circular , Humanos , Neoplasias Pancreáticas/fisiopatologia , RNA Circular/fisiologia
12.
Emerg Med Int ; 2021: 5579402, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33680515

RESUMO

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) remains a big issue of critical care. It is well known that bystander cardiopulmonary resuscitation (CPR) with an automated external defibrillator (AED) used did improve the survival rate. Therefore, CPR education including basic life support (BLS) and AED has been advocated for years. It showed significant improvement of knowledge and willingness to perform CPR through adolescents after the course. However, little is known regarding the ability and learning effectiveness of school students who attend such courses. Therefore, this study aimed to evaluate the CPR effectiveness of both adolescents (12 years old) and adults who undergo the same course of BLS and AED. METHODS: This is a retrospective study. Sixth-grade elementary school students in Northern Taiwan were selected to compare with the adult group. Both took 90 minutes of the BLS and AED course by the doctor with BLS instructor qualification. The primary outcomes were CPR quality and passing or failing the skill examination parameters. The secondary outcome was the posttraining written test and questionnaire of CPR willingness. RESULTS: In the written test, there was a statistical difference in the pretest score except AED knowledge, but no difference was revealed in the posttest score. No statistical difference in CPR quality was noted. In the skill examination, only checking breathing status had statistical difference (elementary group (71%) vs. adult group (86%) (p=0.003)). CONCLUSION: We revealed that sixth-grade elementary students' performance in CPR and AED was similar to that of adults after completing the current 90-minute course. Therefore, we strongly advocate offering CPR and AED courses to 12-year-old children, and these courses should emphasize checking the victim's breathing status.

13.
Risk Manag Healthc Policy ; 14: 771-777, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33654444

RESUMO

PURPOSE: Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is an emerging contagious pathogen that has caused community and nosocomial infections in many countries. This study aimed to evaluate the impact of Coronavirus disease 2019 (COVID-19) on emergency services of the largest medical center in Taiwan by comparing emergency department (ED) usage, turnover, and admission rates before the COVID-19 outbreak with those during the outbreak. MATERIALS AND METHODS: A retrospective cohort study was conducted in the ED of the largest tertiary medical center in Taiwan. Trends of adult, non-trauma patients who visited the ED during February-April 2019 were compared with those during February-April 2020. The number of visits, their dispositions, crowding parameters, and turnover rates were analyzed. The primary outcome was the change in ED attendance between the two periods. The secondary outcomes were changes in hospital admission rates, crowding parameters, and turnover rates. RESULTS: During the outbreak, there were decreased non-trauma ED visits by 33.45% (p < 0.001) and proportion of Taiwan Triage and Acuity Scale (TTAS) 3 patients (p=0.02), with increased admission rates by 4.7% (p < 0.001). Crowding parameters and turnover rate showed significant improvements. CONCLUSION: Comparison of periods before and during the COVID-19 outbreak showed an obvious decline in adult, non-trauma ED visits. The reduction in TTAS 3 patient visits and the increased hospital admission rates provide references for future public-health policy-making to optimise emergency medical resource allocations globally.

14.
Cell Death Dis ; 11(7): 514, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641734

RESUMO

Death domain-associated protein (DAXX) is a complex biological multifunctional protein and is involved in the tumorigenesis and progression of multiple cancers. The accumulation of DAXX in the nucleus is a common phenomenon in tumor cells. However, altering the subcellular localizations of DAXX results in different biological functions, and we also found that its nuclear/cytoplasmic ratio (NCR) was associated with poor prognosis in gastric cancer (GC). In this study, we investigated the effect of cytoplasmic and nuclear DAXX (cDAXX and nDAXX) in GC and the underlying mechanisms. Immunohistochemical detection performed in 323 GC tissues reveled that cDAXX was associated with a better survival, while high nDAXX expression suggested a poorer prognosis outcome. Upregulation of DAXX in the cytoplasm inhibited cell proliferation and promoted apoptosis, whereas downregulation of DAXX in the nucleus displayed opposite effects. Moreover, Transwell assays revealed that DAXX enhanced GC cell migration and invasion. Analysis from the Gene Expression Profile Interactive Analysis (GEPIA) database showed that the expression of DAXX was significantly associated with SUMO-2/3 in GC tissues. Co-immunoprecipitation combined with immunofluorescence analysis indicated that DAXX interacted directly with SUMO-2/3. Subsequently, down-regulating the expression of SUMO-2/3 resulted in altered subcellular localization of DAXX. Bioinformatics analysis showed that RanBP2 may act as SUMO E3 ligase to promote nuclear-plasma transport via combining with RanGAP1. Taken together, our results indicated that DAXX plays opposing roles in GC and suggest a new model whereby cDAXX, nDAXX, and SUMO-2/3 form a molecular network that regulates the subcellular localization of DAXX and thereby modulates its opposing biological effects. Thus, our findings provide a foundation for future studies of DAXX as a novel therapeutic target for patients with GC.


Assuntos
Núcleo Celular/metabolismo , Proteínas Correpressoras/metabolismo , Chaperonas Moleculares/metabolismo , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Neoplasias Gástricas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Proteínas Ativadoras de GTPase/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Invasividade Neoplásica , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Ligação Proteica , Neoplasias Gástricas/patologia , Frações Subcelulares/metabolismo , Sumoilação , Ubiquitina-Proteína Ligases/metabolismo
15.
Sci Rep ; 10(1): 10032, 2020 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-32572100

RESUMO

Cardiopulmonary resuscitation (CPR) training and its quality are critical in improving the survival rate of cardiac arrest. This randomized controlled study investigated the efficacy of a newly developed CPR training program for the public in a Taiwanese setting. A total of 832 adults were randomized to either a traditional or blended (18-minute e-learning plus 30-minute hands-on) compression-only CPR training program. The primary outcome was compression depth. Secondary outcomes included CPR knowledge test, practical test, quality of CPR performance, and skill retention. The mean compression depth was 5.21 cm and 5.24 cm in the blended and traditional groups, respectively. The mean difference in compression depth between groups was -0.04 (95% confidence interval -0.13 to infinity), demonstrating that the blended CPR training program was non-inferior to the traditional CPR training program in compression depth after initial training. Secondary outcome results were comparable between groups. Although the mean compression depth and rate were guideline-compliant, only half of the compressions were delivered with adequate depth and rate in both groups. CPR knowledge and skill retained similarly in both groups at 6 and 12 months after training. The blended CPR training program was non-inferior to the traditional CPR training program. However, there is still room for improvement in optimizing initial skill performance as well as skill retention. Clinical Trial Registration: NCT03586752; www.clinicaltrial.gov.


Assuntos
Reanimação Cardiopulmonar/educação , Adulto , Educação/métodos , Educação a Distância/métodos , Avaliação Educacional , Feminino , Humanos , Masculino
16.
J Am Heart Assoc ; 9(11): e015544, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32458720

RESUMO

Background Should all out-of-hospital cardiac arrest (OHCA) patients be directly transported to cardiac arrest centers (CACs) remains under debate. Our study evaluated the impacts of different transport time and destination hospital on the outcomes of OHCA patients. Methods and Results Data were collected from 6655 OHCA patients recorded in the regional prospective OHCA registry database of Taoyuan City, Taiwan, between January 2012 and December 2016. Patients were matched on propensity score, which left 5156 patients, 2578 each in the CAC and non-CAC groups. Transport time was dichotomized into <8 and ≥8 minutes. The relations between the transport time to CACs and good neurological outcome at discharge and survival to discharge were investigated. Of the 5156 patients, 4215 (81.7%) presented with nonshockable rhythms and 941 (18.3%) presented with shockable rhythms. Regardless of transport time, transportation to a CAC increased the likelihoods of survival to discharge (<8 minutes: adjusted odds ratio [aOR], 1.95; 95% CI, 1.11-3.41; ≥8 minutes: aOR, 1.92; 95% CI, 1.25-2.94) and good neurological outcome at discharge (<8 minutes: aOR, 2.70; 95% CI, 1.40-5.22; ≥8 minutes: aOR, 2.20; 95% CI, 1.29-3.75) in OHCA patients with shockable rhythms but not in patients with nonshockable rhythms. Conclusions OHCA patients with shockable rhythms transported to CACs demonstrated higher probabilities of survival to discharge and a good neurological outcome at discharge. Direct ambulance delivery to CACs should thus be considered, particularly when OHCA patients present with shockable rhythms.


Assuntos
Reanimação Cardiopulmonar , Serviços Médicos de Emergência , Parada Cardíaca Extra-Hospitalar/terapia , Tempo para o Tratamento , Transporte de Pacientes , Adulto , Idoso , Idoso de 80 Anos ou mais , Reanimação Cardiopulmonar/efeitos adversos , Reanimação Cardiopulmonar/mortalidade , Bases de Dados Factuais , Avaliação da Deficiência , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/diagnóstico , Parada Cardíaca Extra-Hospitalar/mortalidade , Parada Cardíaca Extra-Hospitalar/fisiopatologia , Alta do Paciente , Recuperação de Função Fisiológica , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Taiwan , Fatores de Tempo , Resultado do Tratamento
17.
Mol Carcinog ; 59(4): 339-352, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31989722

RESUMO

Diffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that the alter of the cellular cytoskeleton and intercellular adhesion. CD2-associated protein (CD2AP) is one of the critical proteins regulating cytoskeleton assembly and intercellular adhesion. However, no study has investigated the expression and biological significance of CD2AP in gastric cancer (GC) to date. Therefore, the aim of our study was to explore if the expression of CD2AP is associated with any clinical features of GC and to elucidate the underlying mechanism. Immunohistochemistry of 620 patient tissue samples indicated that the expression of CD2AP is downregulated in DGC. Moreover, a low CD2AP level was indicative of poor patient prognosis. In vitro, forced expression of CD2AP caused a significant decrease in the migration and invasion of GC cells, whereas depletion of CD2AP had the opposite effect. Immunofluorescence analysis indicated that CD2AP promoted cellular adhesion and influenced cell cytoskeleton assembly via interaction with the F-actin capping protein CAPZA1. Overall, the upregulation of CD2AP could attenuate GC metastasis, suggesting CD2AP as a novel biomarker for the prognosis and treatment of patients with GC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Movimento Celular/genética , Proteínas do Citoesqueleto/genética , Citoesqueleto/metabolismo , Neoplasias Gástricas/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/genética , Adesão Celular/genética , Linhagem Celular Tumoral , Proteínas do Citoesqueleto/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Interferência de RNA , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia
18.
Front Oncol ; 10: 614096, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33659211

RESUMO

Gastric cancer (GC) is one of the most common malignancies with high mortality and substantial morbidity. Although the traditional treatment strategies for GC revolve around surgery, radiotherapy, and chemotherapy, none have been able to optimally treat most affected patients. To improve clinical outcomes and overcome potential GC resistance, we established a three-dimensional (3D) culturing platform that accurately predicts drug responses in a time- and cost-effective manner. We collected tumor tissues from patients following surgeries and cultured them for 3 days using our protocol. We first evaluated cell proliferation, viability, and apoptosis using the following markers: Ki67 and cleaved caspase 3 (Cas3). We demonstrated that cell viability was maintained for 72 h in culture and that the tumor microenvironments and vascular integrities of the tissues were intact throughout the culture period. We then administered chemotherapeutics to assess drug responses and found differential sensitivity across different patient-derived tissues, enabling us to determine individualized medication plans. Overall, our study validated this rapid, cost-effective, scalable, and reproducible protocol for GC tissue culture that can be employed for drug response assessments. Our 3D culture platform paves a new way for personalized medication in GC and other tumors and can greatly impact future oncological research.

19.
Emerg Med J ; 36(10): 595-600, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31439715

RESUMO

OBJECTIVE: This study determined the impact of the caller's emotional state and cooperation on out-of-hospital cardiac arrest (OHCA) recognition and dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) performance metrics. METHODS: This was a retrospective study using data from November 2015 to October 2016 from the emergency medical service dispatching centre in northern Taiwan. Audio recordings of callers contacting the centre regarding adult patients with non-traumatic OHCA were reviewed. The reviewers assigned an emotional content and cooperation score (ECCS) to the callers. ECCS 1-3 callers were graded as cooperative and ECCS 4-5 callers as uncooperative and highly emotional. The relation between ECCS and OHCA recognition, time to key events and DA-CPR delivery were investigated. RESULTS: Of the 367 cases, 336 (91.6%) callers were assigned ECCS 1-3 with a good inter-rater reliability (k=0.63). Dispatchers recognised OHCA in 251 (68.4%) cases. Compared with callers with ECCS 1, callers with ECCS 2 and 3 were more likely to give unambiguous responses about the patient's breathing status (adjusted OR (AOR)=2.6, 95% CI 1.1 to 6.4), leading to a significantly higher rate of OHCA recognition (AOR=2.3, 95% CI 1.1 to 5.0). Thirty-one callers were rated uncooperative (ECCS 4-5) but had shorter median times to OHCA recognition and chest compression (29 and 122 s, respectively) compared with the cooperative caller group (38 and 170 s, respectively). Nevertheless, those with ECCS 4-5 had a significantly lower DA-CPR delivery rate (54.2% vs 85.9%) due to 'caller refused' or 'overly distraught' factors. CONCLUSIONS: The caller's high emotional state is not a barrier to OHCA recognition by dispatchers but may prevent delivery of DA-CPR instruction. However, DA-CPR instruction followed by first chest compression is possible despite the caller's emotional state if dispatchers are able to skilfully reassure the emotional callers.


Assuntos
Reanimação Cardiopulmonar/métodos , Barreiras de Comunicação , Emoções , Parada Cardíaca Extra-Hospitalar/terapia , Relações Profissional-Paciente , Idoso , Idoso de 80 Anos ou mais , Comportamento Cooperativo , Operador de Emergência Médica/psicologia , Sistemas de Comunicação entre Serviços de Emergência , Feminino , Primeiros Socorros/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/diagnóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Taiwan , Telefone , Fatores de Tempo
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