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OBJECTIVE: This study aims to explore the common genetic basis between respiratory diseases and to identify shared molecular and biological mechanisms. METHODS: This genome-wide pleiotropic association study uses multiple statistical methods to systematically analyse the shared genetic basis between five respiratory diseases (asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, lung cancer and snoring) using the largest publicly available genome wide association studies summary statistics. The missions of this study are to evaluate global and local genetic correlations, to identify pleiotropic loci, to elucidate biological pathways at the multiomics level and to explore causal relationships between respiratory diseases. Data were collected from 27 November 2022 to 30 March 2023 and analysed from 14 April 2023 to 13 July 2023. MAIN OUTCOMES AND MEASURES: The primary outcomes are shared genetic loci, pleiotropic genes, biological pathways and estimates of genetic correlations and causal effects. RESULTS: Significant genetic correlations were found for 10 paired traits in 5 respiratory diseases. Cross-Phenotype Association identified 12 400 significant potential pleiotropic single-nucleotide polymorphism at 156 independent pleiotropic loci. In addition, multitrait colocalisation analysis identified 15 colocalised loci and a subset of colocalised traits. Gene-based analyses identified 432 potential pleiotropic genes and were further validated at the transcriptome and protein levels. Both pathway enrichment and single-cell enrichment analyses supported the role of the immune system in respiratory diseases. Additionally, five pairs of respiratory diseases have a causal relationship. CONCLUSIONS AND RELEVANCE: This study reveals the common genetic basis and pleiotropic genes among respiratory diseases. It provides strong evidence for further therapeutic strategies and risk prediction for the phenomenon of respiratory disease comorbidity.
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Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Humanos , Doenças Respiratórias/genética , Pleiotropia Genética , Doença Pulmonar Obstrutiva Crônica/genética , Asma/genéticaRESUMO
Kazakh mares have attracted widespread attention with their outstanding lactation traits. Lactation is a complex dynamic process regulated by multiple factors. The extensive application of transcriptome sequencing technology enables researchers to further explore this biological issue. This study selected three pregnant and three non-pregnant Kazakh mares as the research subject. Their mammary glands were taken for transcriptome sequencing. The results show that there are 9 lncRNAs and 122 mRNAs differentially expressed between the two groups. GO enrichment analysis shows that there are 175 molecular functions, 59 cellular components, and 555 biological processes, including cellular hormone metabolic process, hormone catabolic process, and I-kappaB kinase/NF-kappaB signaling. KEGG enrichment analysis exhibits that these differential genes are mainly enriched in the NF-kappa B signaling pathway, steroid hormone biosynthesis, breast cancer, ECM-receptor interaction, and MAPK signaling pathway. WNT4, DPP4, and NFKBIA are key nodes regulating breast activation. Conclusions: Through the comparative analysis of the transcriptome data of mammary tissues of pregnant and non-pregnant mares, relevant differentially expressed genes are screened and analyzed. This study provides valuable fundamental data for investigating candidate genes related to the lactation regulation and mammogenesis of Kazakh horses.
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Perfilação da Expressão Gênica , Transcriptoma , Gravidez , Animais , Feminino , Cavalos/genética , Perfilação da Expressão Gênica/métodos , Lactação/genética , RNA Mensageiro/genética , HormôniosRESUMO
BACKGROUND AND AIMS: This prospective study aimed to compare the changes in nutritional status and adverse events among patients with esophageal squamous cell carcinoma who received enteral nutrition through oral intake, PEG, and an enteral nasogastric tube (NGT) during concurrent chemoradiotherapy (CCRT). METHODS: Of 141 included patients, 38, 74, and 29 patients were fed through oral intake, PEG, and NGTs, respectively. The clinical characteristics and baseline nutritional status of the 3 groups were recorded and analyzed. The Patient-Generated Subjective Global Assessment score, skeletal muscle index, and quality of life were evaluated before and after CCRT; the incidence of adverse events during feeding using PEG and NGTs was also recorded. The correlations among the different nutritional pathways and the CCRT-related adverse events (eg, radiation esophagitis and myelosuppression) were assessed. RESULTS: At baseline, the oral intake group had a significantly better nutritional status and lower disease stage than those in the PEG and NGT groups. However, during CCRT, the oral intake group exhibited the most significant decreases in weight and skeletal muscle index. The synchronous chemotherapy completion rate was the highest in the PEG group. Multivariate analysis showed that the planning tumor volume and oral intake and NGT feeding pathways were associated with radiation esophagitis of at least grade 2. CONCLUSIONS: We found that PEG effectively maintained the body weight and skeletal muscle index of patients with esophageal cancer during CCRT. PEG also improved the synchronous chemotherapy completion rate and reduced the occurrence of at least grade 2 radiation esophagitis. (Clinical trial registration number: NCT04199832.).
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Esofagite , Lesões por Radiação , Humanos , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/complicações , Neoplasias Esofágicas/complicações , Estudos Prospectivos , Qualidade de Vida , Quimiorradioterapia/efeitos adversos , Lesões por Radiação/complicações , Esofagite/etiologiaRESUMO
Background: Tumor invasiveness plays a key role in determining surgical strategy and patient prognosis in clinical practice. The study aimed to explore artificial-intelligence-based computed tomography (CT) histogram indicators significantly related to the invasion status of lung adenocarcinoma appearing as part-solid nodules (PSNs), and to construct radiomics models for prediction of tumor invasiveness. Methods: We identified surgically resected lung adenocarcinomas manifesting as PSNs in Peking University People's Hospital from January 2014 to October 2019. Tumors were categorized as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) by comprehensive pathological assessment. The whole cohort was randomly assigned into a training (70%, n=832) and a validation cohort (30%, n=356) to establish and validate the prediction model. An artificial-intelligence-based algorithm (InferRead CT Lung) was applied to extract CT histogram parameters for each pulmonary nodule. For feature selection, multivariate regression models were built to identify factors associated with tumor invasiveness. Logistic regression classifier was used for radiomics model building. The predictive performance of the model was then evaluated by ROC and calibration curves. Results: In total, 299 AIS/MIAs and 889 IACs were included. In the training cohort, multivariate logistic regression analysis demonstrated that age [odds ratio (OR), 1.020; 95% CI, 1.004-1.037; p=0.017], smoking history (OR, 1.846; 95% CI, 1.058-3.221; p=0.031), solid mean density (OR, 1.014; 95% CI, 1.004-1.024; p=0.008], solid volume (OR, 5.858; 95% CI, 1.259-27.247; p = 0.037), pleural retraction sign (OR, 3.179; 95% CI, 1.057-9.559; p = 0.039), variance (OR, 0.570; 95% CI, 0.399-0.813; p=0.002), and entropy (OR, 4.606; 95% CI, 2.750-7.717; p<0.001) were independent predictors for IAC. The areas under the curve (AUCs) in the training and validation cohorts indicated a better discriminative ability of the histogram model (AUC=0.892) compared with the clinical model (AUC=0.852) and integrated model (AUC=0.886). Conclusion: We developed an AI-based histogram model, which could reliably predict tumor invasiveness in lung adenocarcinoma manifesting as PSNs. This finding would provide promising value in guiding the precision management of PSNs in the daily practice.
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BACKGROUND: The incidence of nutritional risk and malnutrition are high in patients with cancer pain. It is very important to choose an effective tool to identify these patients promptly. However, few studies have discussed this issue. The primary objective of this study is to clarify the similarities and differences between the two nutritional screening and assessment tools, and to estimate the anthropometry and biochemical indicators of the patients with cancer pain, with a view to provide help for treatment of these patients. METHOD: Data of 146 patients with cancer pain were collected from August 2018 to May 2019 in the Pain Therapy Department of Tianjin Cancer Hospital. The information of numerical rating scale (NRS), nutritional risk screening-2002 (NRS-2002), patient-generated subjective global assessment (PG-SGA), anthropometry and biochemical indicators were collected for pain assessment, nutritional risk screening, and nutritional status assessment. RESULTS: NRS scores had a positive correlation with NRS-2002 (R = 0.273, P = 0.001) and PG-SGA (R = 0.341, P = 0.000) separately. NRS-2002 and PG-SGA had a significant positive correlation with each other (R = 0.468, P = 0.000). NRS-2002 was finished in a shorter time period (4.2 ± 0.8 min vs. 12.8 ± 0.8 min, P = 0.001), while PG-SGA had a higher detection rate of malnutrition (86.3% vs. 65.8%). In the stepwise multiple regression analysis, NRS (0.258, P = 0.001), PA (-0.297, P = 0.000), TP (0.178, P = 0.030) are the indicators of NRS-2002; and NRS (0.317, P = 0.000), PA (ß = 0.288, P = 0.000) and BMI (-0.281, P = 0.000) are the related variables of PG-SGA. The kappa coefficient was lower than 0.4 (kappa value = 0.396) when choosing the score of NRS-2002 ≥ 3 and PG-SGA ≥ 9 as the diagnostic criteria. If choosing the score of NRS-2002 ≥ 2 and PG-SGA ≥ 9, both the correlation coefficient (R = 0.699, P = 0.000) and the kappa coefficient (kappa value = 0.698, P = 0.000) became more coefficient. CONCLUSIONS: Both NRS-2002 and PG-SGA could identify patients with nutritional risk and malnutrition accurately. NRS-2002 is simpler and takes less time to finish, while PG-SGA is more cumbersome with a higher detection rate of malnutrition. NRS, PA, TP and BMI are the most important reference indicators predicting on nutritional risk index and malnutrition status. We recommend NRS-2002 ≥ 2 as the diagnostic criteria in order to avoid missing the patients with nutritional risk.
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Dor do Câncer , Desnutrição , Neoplasias , Institutos de Câncer , Dor do Câncer/complicações , Dor do Câncer/etiologia , Humanos , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Desnutrição/etiologia , Neoplasias/complicações , Avaliação Nutricional , Estado Nutricional , Medição de RiscoRESUMO
BACKGROUND: Cancer has been considered as the leading cause of death in the world. In patients with cancer, up to 80% display a cachectic period after diagnosis. Cachexia is known to have a negative impact on function, treatment tolerance, higher rates of hospitalizations, and mortality. Anorexia is often used as a warning sign of precachexia. Long-term anorexia may lead to malnutrition and, then, accelerate the occurrence of cachexia. A safe and effective treatment, which can both improve appetite and assist nutritional support for precachexia cancer patients shows its particular important role. METHODS: A retrospective analysis comparing the different therapeutic effects on precachexia cancer patients with anorexia-malnutrition. We recorded 46 patients with the improved-Sijunzi decoction combined with enteral nutrition emulsion (ISJZ group) and 35 patients with single enteral nutrition emulsion (SEN group). The different therapeutic effects of the two groups were observed by recording indicators before and 2 weeks after treatment, including patient-generated subjective global assessment score, quality of life score, Karnofsky performance status scale, Eastern cooperative oncology group scale standard and traditional Chinese medicine syndrome, daily total dietary intake, red blood cells, hemoglobin, prealbumin, albumin, total protein cholinesterase, C-reactive protein, leukocytes, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea nitrogen, and creatinine. RESULTS: ISJZ group exhibited prominent improvement of traditional Chinese medicine syndrome (TCMS), nutritional condition, and quality of life compared with the SEN group (QOL: p=0.0001, PG-SGA: p=0.019, dietary intake: p=0.0001, TCMS: p=0.0001). The levels of HGB (p=0.006), PAlb (p=0.001), Alb (p=0.0001), TP (p=0.008), and ChE (p=0.0001) in the ISJZ group were higher than the SEN group after treatment. Moreover, the ratios of CRP/ALB (p=0.028) and CRP/PALB (p=0.005) in the two groups have obvious differences; they were lower for the ISJZ group than the SEN group. CONCLUSIONS: Enteral nutrition combined with ISJZ decoction is an effective treatment in precachexia cancer patients for the prevention of cachexia. This treatment therapy can alleviate the inflammatory response, improve malnutrition state, and promote the performance status. Tianjin Medical University Cancer Institute and Hospital approved this study (Trial No. 1913).
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BACKGROUND: To investigate the relationship between baseline nutrition status and radiation esophagitis in patients with esophageal cancer treated by radiation therapy. METHODS: A retrospective study was performed on 100 patients with esophageal cancer who was treated with definitive chemoradiotherapy, preoperative chemoradiation and definitive radiotherapy at the Tianjin Medical University Cancer Institute and Hospital from October 2018 and October 2019. We documented the clinical characteristics of patients, including tumor location, clinical stage, treatment, radiation dose, gross tumor volume (GTV), planning tumor volume (PTV) and Atkinson's Dysphagia score (ADS), and we recorded the nutrition status before radiation, including Patient-Generated Subjective Global Assessment (PG-SGA), body mass index (BMI), weight loss percentage in 3 mouths (WL), the level of albumin (ALB), hemoglobin (HB), C-reactive protein (CRP) and Glasgow prognostic score (GPS). These factors were correlated with radiation esophagitis using univariate and multivariate regression analyses. RESULTS: Of 100 patients, 44% patients with PG-SGA score ≥9 at baseline, suggesting severe malnutrition, 41% patients developed grade ≥2 radiation esophagitis. In univariate analysis, dose >40 Gy (P=0.015), PTV ≥495 cm3 (P=0.049), PG-SGA score ≥9 (P=0.001), WL ≥10% (P=0.019) and ALB level <35 g/L (P=0.043) were significantly associated with grade ≥2 radiation esophagitis. Multivariate analysis revealed that PG-SGA score ≥9 (P=0.042) was the independent predictor of radiation esophagitis. CONCLUSIONS: Baseline nutritional status associated with development of grade ≥2 radiation esophagitis in patients with esophageal cancer undergoing radiotherapy.
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Objectives: This study aimed to analyze and evaluate serum insulin-like growth factor-binding protein 2 (IGFBP2) levels as a new biomarker of severe malnutrition in patients with advanced lung cancer.Design and methods: This prospective study involved 59 patients with advanced lung cancer. We detected serum IGFBP2 level by using enzyme-linked immunosorbent assay and analyzed its relationship to clinical characteristics, nutritional status, Glasgow prognostic score (GPS), and survival. Serum albumin and C-reactive protein (CRP) levels were measured, and nutritional status was assessed using Patient-Generated Subjective Global Assessment (PG-SGA). The best cutoff point value for serum IGFBP2 level was established using receiver operating characteristic analysis. Kaplan-Meier method was utilized to analyze the survival curves.Results: Serum IGFBP2 levels were elevated in patients with advanced lung cancer and severe malnutrition. The best cutoff value for serum IGFBP2 level was determined at 363 ng/ml, which could diagnose severe malnutrition with 73.3% sensitivity and 70.5% specificity and was found to be related to albumin, CRP, and GPS. Patients whose serum IGFBP2 levels were higher than 363 ng/ml had poor survival outcome.Conclusion: This study demonstrates the remarkably association between higher serum level of IGFBP2 and severe malnutrition, albumin, CRP, GPS, and survival. Hence, serum IGFBP2 level can be used as a potential biomarker for diagnosis of severe malnutrition in patients with advanced lung cancer.