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INTRODUCTION: Smoking cessation (SC) clinics are a professional SC services in China. However, studies comparing the characteristics and SC rates of smoking populations in SC clinics with those using mobile SC programs are limited. We compared smokers' characteristics, 3-month SC rates, and the factors influencing 3-month SC success, between a large hospital SC clinic and a WeChat SC mini-program. METHODS: Between January and November 2021, 384 participants voluntarily enrolled in either the hospital SC clinic (Group A: n=243) or the WeChat SC mini-program (Group B: n=141). Both groups underwent a 3-month SC intervention, and their SC status was monitored at 24 hours, 1 week, 1 month, and 3 months after quitting. SC rate was defined as the self-reported rate of continuous SC. RESULTS: The 3-month SC rate was higher in Group A (42.4%) than in Group B (24.8%). Participants with middle school education had a lower likelihood of SC success than those with primary school or lower (p=0.014). Employees in the enterprise/business/services industries were more likely to have SC success than farmers (p=0.013). Participants with SC difficulty scores of 0-60 were more successful than those with scores >60 (p=0.001, p=0.000, respectively). Participants who quit smoking due to their illness, or other reasons, had a higher likelihood of SC success than those who quit due to concerns about their own and their family's health (p=0.006, p=0.098, respectively). While the likelihood of SC success was lower in those who quit because of the influence of their environment than in those who quit due to concerns about their own and their family's health (p=0.057). CONCLUSIONS: Both SC clinics and WeChat SC mini-programs achieved satisfactory SC rates. The high accessibility of mobile SC platforms, which save time spent on transportation and medical visits, renders them worth promoting and publicizing as additional SC options for smokers, particularly young smokers.
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Accurate segmentation of lung nodules is the key to diagnosing the lesion type of lung nodule. The complex boundaries of lung nodules and the visual similarity to surrounding tissues make precise segmentation of lung nodules challenging. Traditional CNN based lung nodule segmentation models focus on extracting local features from neighboring pixels and ignore global contextual information, which is prone to incomplete segmentation of lung nodule boundaries. In the U-shaped encoder-decoder structure, variations of image resolution caused by up-sampling and down-sampling result in the loss of feature information, which reduces the reliability of output features. This paper proposes transformer pooling module and dual-attention feature reorganization module to effectively improve the above two defects. Transformer pooling module innovatively fuses the self-attention layer and pooling layer in the transformer, which compensates for the limitation of convolution operation, reduces the loss of feature information in the pooling process, and decreases the computational complexity of the Transformer significantly. Dual-attention feature reorganization module innovatively employs the dual-attention mechanism of channel and spatial to improve the sub-pixel convolution, minimizing the loss of feature information during up-sampling. In addition, two convolutional modules are proposed in this paper, which together with transformer pooling module form an encoder that can adequately extract local features and global dependencies. We use the fusion loss function and deep supervision strategy in the decoder to train the model. The proposed model has been extensively experimented and evaluated on the LIDC-IDRI dataset, the highest Dice Similarity Coefficient is 91.84 and the highest sensitivity is 92.66, indicating the model's comprehensive capability has surpassed state-of-the-art UTNet. The model proposed in this paper has superior segmentation performance for lung nodules and can provide a more in-depth assessment of lung nodules' shape, size, and other characteristics, which is of important clinical significance and application value to assist physicians in the early diagnosis of lung nodules.
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Relevancia Clínica , Médicos , Humanos , Reproducibilidad de los Resultados , Suministros de Energía Eléctrica , Pulmón/diagnóstico por imagen , Procesamiento de Imagen Asistido por ComputadorRESUMEN
INTRODUCTION: Many smokers in China desire to quit, though the success rate among adults is low. This study evaluated the effects of QuitAction, a WeChat smoking cessation platform, summarized the intervention experience of the smoking cessation platform, identified aspects of the platform that necessitated improvement, and provided references for further optimization of the smoking cessation platform. METHODS: This single-arm study was conducted in Hunan, China, from September 2020 to October 2021. Regular smokers, who were aged ≥15 years and willing to quit smoking using QuitAction, were recruited. An in-application questionnaire evaluated participants' baseline smoking status and intention to quit smoking. The QuitAction program included questionnaires regarding the participants' ongoing smoking cessation status at 24 hours, one week, one month and three months after quitting. The smoking cessation procedure was discontinued if the participant had no intention of continuing. The smoking cessation rate, influencing success factors, frequency of use satisfaction, and helpfulness of QuitAction were recorded. RESULTS: A total of 303 participants registered and logged into the QuitAction program, including 59 with incomplete information and 64 with no intention of quitting. The study finally included 180 participants. The smoking cessation rate was 33.9% at 24 hours, 27.2% at one week, 26.1% at one month, and 25.0% at three months. QuitAction was reported as helpful by 94.9% of participants and 95.7% were satisfied with the program. Participants with a quitting difficulty score of 80-100 were less likely to quit smoking than participants with a difficulty score of 0-60 (OR=0.28; 95% CI: 0.10-0.78; p=0.015). Participants using the platform ≥5 times were more likely to quit smoking than those who used the platform <5 times (OR=3.59; 95% CI: 1.51-8.52; p=0.004). CONCLUSIONS: The QuitAction platform provides smoking cessation services that can improve smokers' success rate and improve user experience satisfaction.
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INTRODUCTION: Travel and living environment restrictions, which may have positive or negative effects on smoking-related behaviors, were implemented to limit the COVID-19 pandemic. This study aimed to compare the baseline clinical characteristics and smoking cessation (SC) rate at 3 months of patients in an SC clinic in Hunan Province, China before and during the COVID-19 pandemic and identify influencing factors of successful SC. METHODS: Healthy patients at the SC clinic aged ≥18 years before the COVID-19 pandemic and during the COVID-19 pandemic were divided into groups A and B, respectively. The two groups' demographic data and smoking characteristics were compared, and SC interventions were applied by the same medical staff team through telephone follow-up and counselling during the SC procedure. RESULTS: Groups A and B included 306 and 212 patients, respectively, with no significant differences in demographic data. The SC rates of group A (pre COVID-19) and group B (during the COVID-19 pandemic) at 3 months were 23.5% and 30.7%, respectively, after the first SC visit. Those who chose to quit immediately or within 7 days were more successful than those who did not choose a quit date (p=0.002, p=0.000). Patients who learned about the SC clinic via network resources and other methods were more likely to succeed than those who learned about the clinic from their doctor or hospital publications (p=0.064, p=0.050). CONCLUSIONS: Planning to quit smoking immediately or within 7 days of visiting the SC clinic and learning about the SC clinic via the network media or other methods improved the likelihood of successful SC. SC clinics and the harm of tobacco should be promoted via network media. During consultation, the smokers should be encouraged to quit smoking immediately and establish an SC plan, which would help them to quit smoking.
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Two years after the coronavirus disease 2019 (COVID-19) pandemic, acute hepatitis of unknown etiology in children (AHUCD) began to be reported worldwide. The novel coronavirus and adenovirus were found in pathogen and antibody tests in AHUCD cases reported by the World Health Organization. Children are not exposed to the viruses that children are generally exposed to owing to COVID-19 infection preventive measures such as isolation and wearing masks; therefore, some researchers have speculated that this disease is related to reduced exposure to pathogens. Some scientists have also speculated that the disease is related to liver injury and adenoviral hepatitis, which are the sequelae of COVID-19. Some evidence also suggests a weak association between the disease and COVID-19 vaccination. Therefore, further research and investigation of the pathogenesis, preventive measures, and early treatment of hepatitis of unknown etiology are required. This study aimed to synthesize available evidence to further elucidate this disease in order to treat and prevent it effectively.
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Accurate segmentation of lung nodules is an important basis for the subsequent differentiation of benign and malignant pathological types, which is conducive to early detection of lung cancer. Due to the local feature extraction characteristics of convolution and the limited receptive field of continuous down-sampling, the existing deep convolutional neural networks (CNN) for lung nodules segmentation cause the loss of information of lesion boundaries and locations. To address this issue, a dual-path lung nodules segmentation model based on boundary enhancement and hybrid transformer (DPBET) is proposed in this paper. The model consists of a global path, an edge path, and a feature aggregation module. In the global path, a de-redundant transformer module with explicit guidance is proposed, called Cascade-Axial-Prune Transformer (CAP-Trans). It is combined with CNN to form a hybrid architecture to generate a global representation of the target lesion. In the edge path, an edge detection operator is introduced to construct a lung nodule edge enhancement dataset, which improves the dataset utilization while providing more prior knowledge of the target lesion boundar. In addition, the Down-Attention Sample (DASample) as a basic encoding block is designed to effectively perceive local features of different ranges and scales in the down-sampling process of lung nodule feature extraction. Finally, a feature aggregation module is designed to fuse the outputs of the two paths to get the final segmentation result. Our DPBET can delineate the boundaries of various types of pulmonary nodules, with an average DSC of 89.86% and an average Sensitivity of 90.50% on the public dataset LIDC-IDRI. Compared with the state-of-the-art approaches, a substantial improvement has been achieved. The experimental results demonstrate that DPBET can use edge enhancement to promote the global-edge consistency relationship, and the network architecture is effective in lung nodule segmentation.
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Neoplasias Pulmonares , Tomografía Computarizada por Rayos X , Humanos , Tomografía Computarizada por Rayos X/métodos , Redes Neurales de la Computación , Neoplasias Pulmonares/diagnóstico , PulmónRESUMEN
Chromosomal instability (CIN) covers approximately 65 to 70% of colorectal cancer patients and plays an essential role in cancer progression. However, the molecular features and therapeutic strategies related to those patients are still controversial. R-loop binding proteins (RLBPs) exert significant roles in transcription and replication. Here, integrative colorectal cancer proteogenomic analysis identified two RLBPs subtypes correlated with distinct prognoses. Cluster I (CI), represented by high expression of RLBPs, was associated with the CIN phenotype. While Cluster II (CII) with the worst prognosis and low expression of RLBPs was composed of a high percentage of patients with mucinous adenocarcinoma or right-sided colon cancer. The molecular feature analysis revealed that the active RNA processing, ribosome synthesis, and aberrant DNA damage repair were shown in CI, a high inflammatory signaling pathway, and lymphocyte infiltration was enriched in CII. In addition, we revealed 42 tumor-associated RLBPs proteins. The CI with high expression of tumor-associated proteins was sensitive to drugs targeting genome integrity and EGFR in both cell and organoid models. Thus, our study unveils a significant molecular association of the CIN phenotype with RLBPs, and also provides a powerful resource for further functional exploration of RLBPs in cancer progression and therapeutic application.
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Objective: The aim of our case-control study was to find the influence of lifestyle and comorbidities on COVID-19 susceptibility, identify risk factors and protective factors, and identify ways to encourage people to adopt a healthy lifestyle. Methods: Patients with COVID-19 were matched with non-COVID-19 participants in a ratio of 1:2. Univariate analysis was performed using the chi-square test, and multivariate analysis was performed using conditional logistic regression. Results: Multivariate analysis using conditional logistic regression found that alcohol consumption (AC) and a bland diet increased the risk of COVID-19, while college degrees and above, smoking, drinking tea, and exercise, especially walking, significantly reduced the risk of COVID-19. Conclusion: After removing the effects of demographic factors, the study demonstrated that AC significantly reduced the ability of the body to resist COVID-19 infection. Moreover, following a bland diet increased the susceptibility to COVID-19. Notably, people who drank tea and performed regular exercises, especially walking, were significantly less likely to be infected with COVID-19. College degree or above relative illiteracy is COVID-19 protective factors of infection.
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COVID-19 , Adulto , Consumo de Bebidas Alcohólicas , Areca/efectos adversos , COVID-19/epidemiología , Estudios de Casos y Controles , Humanos , Estilo de Vida , Factores de Riesgo , SARS-CoV-2RESUMEN
DEAD-box RNA helicases belong to a large group of RNA-processing factors and play vital roles unwinding RNA helices and in ribosomal RNA biogenesis. Emerging evidence indicates that RNA helicases are associated with genome stability, yet the mechanisms behind this association remain poorly understood. In this study, we performed a comprehensive analysis of RNA helicases using multiplatform proteogenomic databases. More than 50% (28/49) of detected RNA helicases were highly expressed in multiple tumor tissues, and more than 60% (17/28) of tumor-associated members were directly involved in DNA damage repair (DDR). Analysis of repair dynamics revealed that these RNA helicases are engaged in an extensively broad range of DDR pathways. Among these factors is DDX21, which was prominently upregulated in colorectal cancer. The high expression of DDX21 gave rise to frequent chromosome exchange and increased genome fragmentation. Mechanistically, aberrantly high expression of DDX21 triggered inappropriate repair processes by delaying homologous recombination repair and increasing replication stress, leading to genome instability and tumorigenesis. Treatment with distinct chemotherapeutic drugs caused higher lethality to cancer cells with genome fragility induced by DDX21, providing a perspective for treatment of tumors with high DDX21 expression. This study revealed the role of RNA helicases in DNA damage and their associations with cancer, which could expand therapeutic strategies and improve precision treatments for cancer patients with high expression of RNA helicases. SIGNIFICANCE: The involvement of the majority of tumor-associated RNA helicases in the DNA damage repair process suggests a new mechanism of tumorigenesis and offers potential alternative therapeutic strategies for cancer.
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ARN Helicasas DEAD-box , Neoplasias , Transformación Celular Neoplásica , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , Daño del ADN/genética , Reparación del ADN/genética , Inestabilidad Genómica , Humanos , Neoplasias/genética , Neoplasias/terapia , ARNRESUMEN
PURPOSE: Radioresistance contributes to poor clinical therapeutic efficacy in most cancers. Emerging evidence shows that aberrant DNA damage repair is involved in radioresistance. This study aimed to elucidate the mechanism for radioresistance and explore the precise treatment to sensitize the radioresistant tumors. METHODS AND MATERIALS: Real-time polymerase chain reaction and Western blot were used to confirm the differential expression of epithelial cell transforming 2 (ECT2) in irradiation-resistant and sensitive cell lines. Laser microirradiation was used to examine the ribosome DNA (rDNA) damage response of ECT2. Biotin-identification, in vivo, in vitro binding assay, and dot blotting were used to confirm the interaction of ECT2 and PARP1. The xenograft mouse model and cell survival assay were used to assess the irradiation sensitivity with or without PARP1 inhibitor. RESULTS: We found the expression of ECT2 correlates with sensitivity to radiation therapy in both lung cancer and nasopharyngeal carcinoma. We demonstrated that low expression of ECT2 causes radioresistance, mainly by protecting rDNA in nucleoli from persistent irradiation exposure through transcriptional recovery prevention. ECT2 is recruited to the rDNA damage site in an ataxia-telangiectasia-mutated RNA polymerase I dependent manner. The recruited ECT2 interacts with PARP1 and facilitates the disassociation of PARP1 from rDNA in nucleoli. Thus, ECT2 deficiency results in sustained activation of PARP1, which subsequently inhibits nucleolar transcription and results in a low frequency of rDNA exposure under DNA damage. PARP inhibition synergized with irradiation can sensitize radioresistant tumors with low ECT2 expression. CONCLUSIONS: Our study provides a potential perspective for the application of PARP inhibitor to sensitize low-ECT2 expressing tumors to radiation therapy.
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Reparación del ADN , Neoplasias Nasofaríngeas , Animales , Línea Celular Tumoral , Daño del ADN , ADN Ribosómico , Células Epiteliales/metabolismo , Humanos , Ratones , Proteínas Proto-Oncogénicas , Tolerancia a Radiación/genéticaRESUMEN
INTRODUCTION: Nausea and vomiting (NV) affect up to 85% of pregnant women, which has multiple effects on pregnancy outcome. The truth etiology of nausea and vomiting in pregnancy (NVP) is still unknown. Considering the potential teratogenic effect in fetus due to chemical drugs, ginger can be used to treat nausea and vomiting during pregnancy. Reports have shown that ginger can reduce the severity of NV, however, these results are controversial. Therefore, this meta-analysis aims to explore the effect of ginger in the treatment of nausea and vomiting during pregnancy compared with placebo and vitamin B6. METHODS: The randomized control trials (RCTs) on the association with ginger and pregnancy-related nausea and vomiting were searched and identified in two databases Web of Science and PubMed (up to April 2019). Stata software was used to conduct meta-analysis. In addition, the source of heterogeneity explored by metaregression, sensitivity analysis, subgroup analyses, the publication bias were assessed by Egger's tests and Funnel plot, p < .05 was considered to be significant. RESULTS: Thirteen studies involving 1174 subjects were included in this meta-analysis. The result demonstrated that ginger intervention has significant effect in improving general symptom of NVP [OR = 7.475, 95% CI = (4.133, 13.520), I2 = 30.1%], relieving severity of nausea [SMD = 0.821, 95% CI = (0.585, 1.056), I2 = 38.9%], but not significant in reducing vomiting [SMD = 0.549, 95% CI = (-0.268, 1.365), I2 = 91.4%], compared with placebo. Besides, ginger intervention has no significant effect on improving general symptom of NVP [OR = 1.239, 95% CI = (0.495, 3.102), I2 = 57.3%], relieving severity of nausea [SMD = 0.199, 95% CI = (-0.102, 0.500), I2 = 65.7%], reducing vomiting [SMD = 0.331, 95% CI = (-0.145, 0.808), I2 = 85.9%], compared with vitamin B6. CONCLUSIONS: Ginger supplementation significantly relieve general NVP symptom and nausea compared with placebo, but no significant effect on vomiting. Moreover, ginger is more effective than vitamin B6 in treating NVP, although, there were no significant differences. Further, rigidly designed RCTs with larger sample sizes are needed to verify the effectiveness of ginger supplementation for treatment NVP compared with vitamin B6.
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Antieméticos , Complicaciones del Embarazo , Zingiber officinale , Antieméticos/uso terapéutico , Femenino , Humanos , Náusea/tratamiento farmacológico , Fitoterapia , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Resultado del Embarazo , Vitamina B 6/uso terapéutico , Vómitos/tratamiento farmacológicoRESUMEN
BACKGROUND AND OBJECTIVES: To evaluate the effect of oral nutritional supplements (ONS) on community elderly people with malnutrition or risk of malnutrition. METHODS AND STUDY DESIGN: A single arm intervention trial for 3 months was conducted. Whole nutrient powder was given to all the participants. Dietary intakes were measured by 3-day diet record. Nutritional status was evaluated using body weight, body mass index (BMI), calf circumference (CC), and Mini Nutritional Assessment Short-Form (MNA-SF) scores. Muscle mass was measured by bioimpedance analysis (BIA). All these parameters as well as muscle strength, physical function, and quality of life were measured at both the baseline and the end. RESULTS: Compared with the baseline, ONS increased protein intake (58.32±16.67 vs 41.90±18.49 g/d, p<0.001), body weight (57.03±8.31 vs 56.68±8.23 kg, p<0.05), BMI (22.16±2.13 vs 22.02±2.08 kg/m2, p<0.05), CC (34.21±2.53 vs 33.80±2.53 cm, p<0.001), MNA-SF scores (12.61±1.43 vs 10.48±0.99, p<0.05), hand grip strength (24.54±8.05 vs 23.27±7.74 kg, p<0.001), and 6-m gait speed (1.11±0.33 vs 0.96±0.28 m/s, p<0.001). Moreover, SF-36 scores of the overall subjects have been improved in all dimensions (p<0.05). CONCLUSIONS: The study demonstrated that ONS can effectively increase protein intake and improve nutritional status, muscle strength, physical function and quality of life of the elderly with malnutrition or malnutrition risk in communities.
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Desnutrición , Estado Nutricional , Anciano , Evaluación Geriátrica , Fuerza de la Mano , Humanos , Evaluación Nutricional , Calidad de VidaRESUMEN
BACKGROUND AND OBJECTIVES: Malnutrition is implicated as a key modifiable risk factor for sarcopenia. As such, a dietary pattern analysis, rather than an analysis of single food items or nutrients, may provide insights into the comprehensive contribution of diet and nutrition to the risk of sarcopenia. Accordingly, the aim of this study was to evaluate the relationships between main dietary patterns and sarcopenia. METHODS AND STUDY DESIGN: A total of 591 participants aged over 40 years were included in this cross-sectional study. A validated food-frequency questionnaire was used to assess their dietary intake, and principal component analysis (PCA) was used to identify the main dietary patterns. A multivariate logistic regression model was used to explore the associations between their main dietary patterns and the risk of sarcopenia. RESULTS: This study identified 56 cases of sarcopenia, equating to an overall detection rate of 9.48%. The PCA revealed four major dietary patterns among the participants: "coarse cereals and vegetables"; "beverages and animal organs"; "poultry, fish and shrimp"; and "fruits and pasta". After adjusting for age, sex, physical activity and smoking, individuals with the "coarse cereals and vegetables" dietary pattern had a 63.0% reduction in the risk of sarcopenia. CONCLUSIONS: The "coarse cereals and vegetables" dietary pattern is negatively correlated with sarcopenia, and may reduce the risk of sarcopenia.
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Sarcopenia , Anciano , Animales , China/epidemiología , Estudios Transversales , Dieta , Conducta Alimentaria , Frutas , Humanos , Sarcopenia/epidemiología , Encuestas y Cuestionarios , VerdurasRESUMEN
Maternal diet is an important potential factor associated with the risk of preeclampsia. However, it is unclear whether adherence to a Dietary Approaches to Stop Hypertension (DASH)-style diet can reduce the development of preeclampsia. To examine the potential association, we conducted a hospital-based case-control study at the First Affiliated Hospital of Zhengzhou University, China. A total of 449 cases with preeclampsia and 449 controls were studied. Dietary information was collected using a validated food frequency questionnaire (FFQ). DASH scores were calculated according to nutrients/food emphasised or minimised in the DASH diet. The calculated DASH scores ranged from 11 to 38 for all of the participants, and the DASH scores of the cases were significantly lower than those of the controls (23.48 ± 4.58 vs 24.51 ± 4.51; p = 0.001). Participants in the fourth quartile of the DASH score were 45% less likely to have preeclampsia than those in the first quartile in the crude model (Q4 vs Q1, odds ratio [OR]: 0.55; 95% confidence interval [CI]: 0.38, 0.80; ptrend = 0.001). The relationship remained significant in the model adjusted for multiple confounders, especially for major risk factors of preeclampsia (OR: 0.53; 95% CI: 0.36, 0.78; ptrend = 0.001). Our findings suggest an inverse relationship between adherence to a DASH-style diet and the odds of preeclampsia. Further larger-scale cohort studies or randomised controlled trials are warranted to confirm these relationships.
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Enfoques Dietéticos para Detener la Hipertensión/métodos , Hipertensión/prevención & control , Hipertensión/fisiopatología , Preeclampsia/prevención & control , Preeclampsia/fisiopatología , Adulto , Índice de Masa Corporal , Estudios de Casos y Controles , China , Dieta , Femenino , Humanos , Modelos Logísticos , Oportunidad Relativa , Embarazo , Factores de RiesgoRESUMEN
Tumor acquired radioresistance remains as the major limit in cancer radiotherapy (RT). Rab25, a receptor recycling protein, has been reported to be enhanced in tumors with aggressive phenotype and chemotherapy resistance. In this study, elevated Rab25 expression was identified in an array of radioresistant human cancer cell lines, in vivo radioresistant xenograft tumors. Clinical investigation confirmed that Rab25 expression was also associated with a worse prognosis in patients with lung adenocarcinoma (LUAD) and nasopharyngeal carcinoma (NPC). Enhanced activities of EGFR were observed in both NPC and LUAD radioresistant cells. Rab25 interacts with EGFR to enhance EGFR recycling to cell surface and to decrease degradation in cytoplasm. Inhibition of Rab25 showed synergized radiosensitivity with reduced aggressive phenotype. This study provides the clinical and experimental evidence that Rab25 is a potential therapeutic target to alleviate the hyperactive EGFR signaling and to prevent RT-acquired tumor resistance in patients with LUAD and NPC.
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Resistance to radiation of cancer cells can be either intrinsic or acquired, leading to treatment failure. In response to DNA damage caused by IR, cancer cells are arrested in cell cycle showing limited proliferation and increased apoptosis. However, radiation-resistant cells are able to overcome the cell cycle block and proceed to proliferation, for which the detailed mechanism remains to be elucidated. In the present study, we showed that radioresistant cells exhibited a recoverable G2/M phase during prolonged cell cycle and manifested lower apoptosis rate and more colony formation. RNA-seq analysis revealed that glutamine synthetase (GS, GLUL) gene was highly expressed in radioresistant cancer cells in comparison with the parental cells, which was in accordance with the G2/M arrest after ionizing radiation. Knocking out of GS in radioresistant cells resulted in a delayed G2/M recovery and lowered proliferation rate after ionizing radiation treatment, which was accompanied with increased inhibitory phosphorylation of CDK1 at Y15 and downregulated Cdc25B, a dual specific phosphatase of CDK1. Moreover, there was an enhanced complex formation of CDK1 and Cyclin B1 when the cells were rescued by re-introducing GS. In vivo, knocking down of GS significantly sensitized CNE2-R xenografts to RT in mice. In this study, we demonstrate a novel role of glutamine synthetase independent of metabolic function in promoting recovery from G2/M arrest caused by ionizing radiation, thus, causing cancer cell resistance to radiotherapy.
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Puntos de Control de la Fase G2 del Ciclo Celular , Glutamato-Amoníaco Ligasa/metabolismo , Puntos de Control de la Fase M del Ciclo Celular , Neoplasias Nasofaríngeas/radioterapia , Tolerancia a Radiación , Radiación Ionizante , Animales , Apoptosis , Proliferación Celular , Glutamato-Amoníaco Ligasa/genética , Humanos , Ratones , Ratones Desnudos , Neoplasias Nasofaríngeas/enzimología , Neoplasias Nasofaríngeas/patología , Transducción de Señal , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVES: Malnutrition is the most common complication of patients with esophageal cancer and can lead to poor prognosis and death. Good nutritional status has been shown to help improve patient outcomes and reduce complications. In the absence of specific evidence on the effect of nutrition in patients with esophageal cancer, the purpose of this study was to investigate the effect of whole-course nutrition management on the prognosis and complications of chemoradiotherapy in patients with esophageal cancer through a randomized controlled trial. METHODS: A total of 96 patients with esophageal cancer treated with concurrent chemoradiation were randomized to an intervention group (treated with whole-course nutrition management from the Nutrition Support Team) and a control group (treated with the general nutritional method) for approximately 6 wk. Dietary surveys and body measurements were conducted at baseline and every day thereafter. Patient-generated Subjective Global Assessment score, blood index, quality of life, and psychological condition were assessed at baseline and every week before discharge. Complications (e.g., radiation esophagitis, myelosuppression, and skin symptoms), completion rates of therapy, short-term efficacy evaluation, as well as clinical outcomes were measured. RESULTS: A total of 85 patients completed the study (intervention groupâ¯=â¯45; control groupâ¯=â¯40). There were significant differences in the changes of serum albumin and total protein between the two groups throughout the trial (P < 0.05). Complications (e.g., radioactive esophagitis, skin symptom of complications) and quality of life were statistically different before and after the intervention (P < 0.05). The difference in the change of other indicators was not statistically significant. CONCLUSIONS: Whole-course nutrition management can improve the nutritional status of patients with esophageal cancer treated with concurrent chemoradiotherapy, reduce the severity of radiation esophagitis and radiation skin reactions, improve the quality of life, and relieve depressive symptoms.
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Quimioradioterapia , Neoplasias Esofágicas/terapia , Desnutrición/terapia , Terapia Nutricional/métodos , Anciano , Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/fisiopatología , Femenino , Humanos , Masculino , Desnutrición/etiología , Persona de Mediana Edad , Estado Nutricional , Calidad de Vida , Resultado del TratamientoRESUMEN
The global outbreak of the coronavirus disease 2019 (COVID-19) pandemic occurred in late 2019 and early 2020. The factors that influence disease severity should be of clinical concern. Existing findings on the effects of smoking on COVID-19 are also controversial and need to be confirmed by further research. In addition, the effects of alcohol consumption and betel quid (BQ) chewing on COVID-19 are unclear. The aim of this study was to examine the demographic characteristics of COVID-19 patients and the effects of smoking, drinking, BQ chewing, and underlying diseases on the severity of COVID-19. A retrospective study was conducted on 91 patients with confirmed cases of COVID-19 hospitalized in Yueyang, Hunan Province, China from 21 January to 8 March, 2020. Patient demographic data, and information on smoking, drinking and BQ chewing, and underlying diseases were extracted from the patient electronic medical records (EMR) and telephone interviews. The chi-square test was used to conduct a univariate analysis of the factors influencing the severity of COVID-19, and ordinal logistic regression analysis was used to identify the factors related to the severity of COVID-19. The results showed that the rates of smoking, drinking and BQ chewing were 15.4, 26.4, and 7.1%, respectively, there was no significant relationship between these lifestyle factors and the severity of COVID-19 (P > 0.05). However, underlying diseases such as diabetes [odds ratio (OR) = 7.740, 95% confidence interval (CI):1.000-60.740, P = 0.050], source of infection (OR = 0.180, 95% CI: 0.030-0.980, P = 0.049), and employment status (retired/unemployed vs. employed: OR = 29.430, 95% CI, 1.050 - 822.330, P = 0.047) were significant independent predictors of severe COVID-19 infection. These individuals should be informed of methods to increase personal protection, and doctors should prevent these individuals from developing serious diseases. It is important to pay attention to the source of infection and timely medical treatment. This study showed that the clinical classification of COVID-19 was associated with patients with diabetes, source of infection, and retired/unemployed. Therefore in the clinical practice of COVID-19 should be more concern these factors. Although no statistical significance was found in smoking, drinking alcohol, BQ chewing, and severity of COVID-19 patients, more studies have confirmed that are harmful and risk factors for underlying diseases in the population. Health authorities should formulate policies to publicize the harmful effects of smoking, drinking, and betel nut chewing and promote a healthy lifestyle.
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Radiation resistance is a critical problem in radiotherapy for cancer. Radiation kills tumor cells mainly through causing DNA damage. Thus, efficiency of DNA damage repair is one of the most important factors that limits radiotherapy efficacy. Glutamine physiologically functions to generate protein and nucleotides. Here, we study the impact of glutamine metabolism on cancer therapeutic responses, in particular under irradiation-induced stress. We show that radiation-resistant cells possessed low glycolysis, mitochondrial respiration, and TCA cycle but high glutamine anabolism. Transcriptome analyses revealed that glutamine synthetase (GS), an enzyme catalyzing glutamate and ammonia to glutamine, was responsible for the metabolic alteration. ChIP and luciferase reporter assays revealed that GS could be transcriptionally regulated by STAT5. Knockdown of GS delayed DNA repair, weakened nucleotide metabolism, and enhanced radiosensitivity both in vitro and in vivo. Our data show that GS links glutamine metabolism to radiotherapy response through fueling nucleotide synthesis and accelerating DNA repair.
Asunto(s)
Daño del ADN , Reparación del ADN , Glutamato-Amoníaco Ligasa/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Nucleótidos/metabolismo , Tolerancia a Radiación , Animales , Línea Celular Tumoral , Glutamato-Amoníaco Ligasa/genética , Glutamina/genética , Glutamina/metabolismo , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Proteínas de Neoplasias/genética , Neoplasias/genética , Nucleótidos/genéticaRESUMEN
BACKGROUND: Many studies have demonstrated that a higher radiotherapy dose is associated with improved outcomes in non-small-cell lung cancer (NSCLC). We performed a dosimetric planning study to assess the dosimetric feasibility of intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost (SIB) in locally advanced NSCLC. METHODS: We enrolled twenty patients. Five different dose plans were generated for each patient. All plans were prescribed a dose of 60 Gy to the planning tumor volume (PTV). In the three SIB groups, the prescribed dose was 69 Gy, 75 Gy, and 81 Gy in 30 fractions to the internal gross tumor volume (iGTV). RESULTS: The SIB-IMRT plans were associated with a significant increase in the iGTV dose (P < 0.05), without increased normal tissue exposure or prolonged overall treatment time. Significant differences were not observed in the dose to the normal lung in terms of the V5 and V20 among the four IMRT plans. The maximum dose (Dmax) in the esophagus moderately increased along with the prescribed dose (P < 0.05). CONCLUSIONS: Our results indicated that escalating the dose by SIB-IMRT is dosimetrically feasible; however, systematic evaluations via clinical trials are still warranted. We have designed a further clinical study (which is registered with ClinicalTrials.gov, number NCT02841228).