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Background: The long-term prognosis of heart failure with preserved ejection fraction (HFpEF) is influenced by malnutrition. Currently, there's a deficit in objective and comprehensive nutritional assessment methods to evaluate the nutritional status and predicting the long-term outcomes of HFpEF patients. Methods: Our retrospective study included two hundred and eighteen elderly HFpEF patients admitted to the cardiovascular ward at the Air Force Medical Centre from January 2016 to December 2021. Based on follow-up outcomes, patients were categorized into all-cause death (99 cases) and Survival (119 cases) groups. We compared general data, laboratory results, and nutritional indexes between groups. Differences in subgroups based on Triglyceride-Total Cholesterol-Body Weight Index (TCBI), Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), and Controlled Nutrition Score (CONUT) were analyzed using Kaplan-Meier survival curves and log-rank test. COX regression was used to identify all-cause mortality risk factors, and the predictive accuracy of the four nutritional indices was assessed using receiver operating characteristic (ROC) curves and Delong test analysis. Results: A total of 101 (45.41%) HFpEF patients experienced all-cause mortality during 59.02 ± 1.79 months of follow-up. The all-cause mortality group exhibited lower GNRI and PNI levels, and higher CONUT levels than the Survival group (p < 0.05). Kaplan-Meier analysis revealed lower cumulative survival in the low GNRI ( ≤ 96.50) and low PNI ( ≤ 43.75) groups, but higher in the low CONUT ( ≤ 2) group, compared to their respective medium and high-value groups. Multifactorial COX regression identified low PNI ( ≤ 43.75) as an independent all-cause mortality risk factor in elderly HFpEF patients. ROC and Delong's test indicated PNI (area under the curve [AUC] = 0.698, 95% confidence interval [CI] 0.629-0.768) as a more effective predictor of all-cause mortality than TCBI (AUC = 0.533, 95% CI 0.456-0.610) and CONUT (AUC = 0.621, 95% CI 0.547-0.695; p < 0.05). However, there was no significant difference compared to GNRI (AUC = 0.663, 95% CI 0.590-0.735; p > 0.05). Conclusions: In elderly HFpEF patients a PNI ≤ 43.75 was identified as an independent risk factor for all-cause mortality. Moreover, PNI demonstrates superior prognostic performance in predicting all-cause mortality in elderly patients with HFpEF when compared to TCBI, GNRI, and COUNT.
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OBJECTIVE: Prostate hyperplasia and cancer are more prevalent in middle-aged and elderly men. Previous studies have linked both disorders to androgen receptors. Herein, efforts were made to identify factors associated with prostate cancer in patients ≥60 years, aiming to enhance their health management. METHODS: An analytical framework was established utilizing the "Prostate Cancer Early Warning Dataset" from the National Clinical Medical Science Data Center. Variables selection was conducted through LASSO regression, followed by multifactorial logistic stepwise regression to construct a predictive model. RESULTS: A total of 1,502 patients with BPH and 294 with combined PCa were hereby included. Multivariate regression delineated several independent predictors of PCa coexistence, including age (OR [95% CI]: 1.06 [1.04-1.09], p < 0.001), fPSA/tPSA ratio (OR [95% CI]: 0.01 [0.002-0.05], p < 0.001), serum inorganic phosphorus (OR [95% CI]: 5.85 [2.61-13.15], p < 0.001), globulin levels (OR [95% CI]: 1.06 [1.02-1.11], p = 0.005), serum potassium (OR [95% CI]: 0.58 [0.40-0.86], p = 0.006), low-density lipoprotein (LDL) cholesterol (OR [95% CI]: 1.28 [1.06-1.54], p = 0.009), among others. CONCLUSION: The analysis revealed connections between PCa occurrence in men aged over 60 and BPH, along with specific serum biomarkers such as inorganic phosphorus, globulin, LDL cholesterol, lower fPSA/tPSA ratios and serum potassium.
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Hiperplasia Prostática , Neoplasias de la Próstata , Humanos , Masculino , Hiperplasia Prostática/sangre , Hiperplasia Prostática/epidemiología , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/epidemiología , Anciano , Persona de Mediana Edad , Factores de Riesgo , Antígeno Prostático Específico/sangre , Factores de Edad , Anciano de 80 o más Años , Modelos LogísticosRESUMEN
The complex mechanism of colorectal cancer development is closely associated with epigenetic modifications and is caused by overexpression and/or inactivation of oncogenes. Histone modifying enzymes catalyze histone modifications to alter gene expression, which plays a crucial role in the development and progression of colorectal cancer. Currently, there is more frequent study on histone acetylation, methylation, and phosphorylation, and their mechanisms in colorectal cancer development are clearer. This article elaborates on the role of histone modification in epigenetics in colorectal cancer development and discusses recent advances in using it as biomarkers and therapeutic targets for the treatment of colorectal cancer. The review aims to demonstrate the significant role of histone modification as a new therapeutic target in colorectal cancer and provides insights into the novel diagnostic and therapeutic options it offers.
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Background: Accurate detection of atrial fibrillation (AF) recurrence after catheter ablation is crucial. In this study, we aimed to conduct a systematic review of machine-learning-based recurrence detection in the relevant literature. Methods: We conducted a comprehensive search of PubMed, Embase, Cochrane, and Web of Science databases from 1980 to December 31, 2022 to identify studies on prediction models for AF recurrence risk after catheter ablation. We used the prediction model risk of bias assessment tool (PROBAST) to assess the risk of bias, and R4.2.0 for meta-analysis, with subgroup analysis based on model type. Results: After screening, 40 papers were eligible for synthesis. The pooled concordance index (C-index) in the training set was 0.760 (95% confidence interval [CI] 0.739 to 0.781), the sensitivity was 0.74 (95% CI 0.69 to 0.77), and the specificity was 0.76 (95% CI 0.72 to 0.80). The combined C-index in the validation set was 0.787 (95% CI 0.752 to 0.821), the sensitivity was 0.78 (95% CI 0.73 to 0.83), and the specificity was 0.75 (95% CI 0.65 to 0.82). The subgroup analysis revealed no significant difference in the pooled C-index between models constructed based on radiomics features and those based on clinical characteristics. However, radiomics based showed a slightly higher sensitivity (training set: 0.82 vs. 0.71, validation set: 0.83 vs. 0.73). Logistic regression, one of the most common machine learning (ML) methods, exhibited an overall pooled C-index of 0.785 and 0.804 in the training and validation sets, respectively. The Convolutional Neural Networks (CNN) models outperformed these results with an overall pooled C-index of 0.862 and 0.861. Age, radiomics features, left atrial diameter, AF type, and AF duration were identified as the key modeling variables. Conclusions: ML has demonstrated excellent performance in predicting AF recurrence after catheter ablation. Logistic regression (LR) being the most widely used ML algorithm for predicting AF recurrence, also showed high accuracy. The development of risk prediction nomograms for wide application is warranted.
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BACKGROUND: Several proteins in the tripartite-motif (TRIM) family are associated with the development of colorectal cancer (CRC), but research on the role of TRIM69 was lacking. The present study examined the correlation between TRIM69 expression and colon adenocarcinoma (COAD). METHODS: mRNA sequencing data for COAD patients was extracted from The Cancer Genome Atlas to analyze correlations between TRIM69 expression and patients' clinical features as well as survival. Potential associations with immune cells and chemosensitivity also were predicted using various algorithms in the TIMER, Limma, clusterProfiler, GeneMANIA, and Gene Set Cancer Analysis platforms. Subsequently, polymerase chain reaction analysis and immunohistochemical staining were used to detect TRIM69 expression in COAD tissue samples from real-world patients. RESULTS: TRIM69 expression was lower in COAD tissues than in normal tissues and correlated with the pathologic stage and metastasis (M category). Additionally, TRIM69 was found to be involved in several immune-related pathways, notably the NOD-like signaling pathway. These results suggest that high TRIM69 expression has the potential to enhance tumor sensitivity to 5-fluorouracil and programmed cell death protein 1 (PD-1) blockers. CONCLUSIONS: From our findings that TRIM69 expression was significantly reduced in COAD compared with non-cancer tissues and associated with pathologic stage and metastasis, we conclude that increasing TRIM69 expression and/or activity may help to improve therapeutic outcomes. Accordingly, TRIM69 represents a potentially valuable marker of metastasis and target for adjuvant therapy in COAD.
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Adenocarcinoma , Neoplasias del Colon , Humanos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Fluorouracilo/uso terapéutico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Receptor de Muerte Celular Programada 1 , Algoritmos , Proteínas de Motivos Tripartitos/genética , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
OBJECTIVES: To investigate the role of cell cycle protein-dependent kinase regulatory subunit 1B (CKS1B) in driving the aggressive and rapid proliferation observed in pancreatic cancer. METHODS: A comprehensive analysis was carried out using raw mRNA information and data from 2 databases: the cancer genome atlas and gene expression omnibus. The differential expression of CKS1B at the mRNA and tissue levels in cancer and adjacent paracancerous tissues were assessed. Additionally, the relationship of CKS1B expression and overall survival (OS) rate was investigated using Kaplan-Meier survival curves. Potential molecular mechanisms by which CKS1B may influence the biological characteristics of pancreatic cancer were explored using resources available within the encyclopedia of RNA interactomes database. RESULTS: The CKS1B exhibited significant differential expression at the mRNA as well as protein levels. A correlation with statistical significance between CKS1B expression and N stage, age, and alcohol consumption was observed. Notably, high CKS1B expression was determined as a predictive factor for worse OS. Furthermore, the analysis revealed a potential synergistic role between CKS1B and the molecule PKMYT1, which could impact the ATR-Chk1-Cdc25 signaling pathway and disrupt the G2/M checkpoint within the cell cycle, ultimately promoting abnormal tumor proliferation. CONCLUSION: The CKS1B may serve as a novel potential prognostic factor in pancreatic cancer and is involved in the abnormal proliferation biology phenotype by mediating cell cycle signaling pathways.
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Quinasas CDC2-CDC28 , Neoplasias Pancreáticas , Humanos , Quinasas CDC2-CDC28/genética , Ciclo Celular/genética , Proliferación Celular/genética , Proteínas de la Membrana/genética , Neoplasias Pancreáticas/genética , Fenotipo , Pronóstico , Proteínas Serina-Treonina Quinasas/genética , Proteínas Tirosina Quinasas/genética , ARN Mensajero/genética , Transducción de Señal/genéticaRESUMEN
Background: This systematic review and meta-analysis aimed to explore the effects of different sodium-glucose cotransporter-2 inhibitors (SGLT2i) on prognosis and cardiac structural remodeling in patients with heart failure (HF). Methods: Relevant studies published up to 20 March 2024 were retrieved from PubMed, EMBASE, Web of Science, and Cochrane Library CNKI, China Biomedical Literature Service, VIP, and WanFang databases. We included randomized controlled trials of different SGLT2i and pooled the prognosis data of patients with HF. We compared the efficacy of different SGLT2i in patients with HF and conducted a sub-analysis based on left ventricular ejection fraction (LVEF). Results: We identified 77 randomized controlled trials involving 43,561 patients. The results showed that SGLT2i significantly enhanced outcomes in HF, including a composite of hospitalizations for HF and cardiovascular death, individual hospitalizations for HF, Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, left atrial volume index (LAVi), and LVEF among all HF patients (P < 0.05) compared to a placebo. Sotagliflozin was superior to empagliflozin [RR = 0.88, CI (0.79-0.97)] and dapagliflozin [RR = 0.86, CI (0.77-0.96)] in reducing hospitalizations for HF and CV death. Dapagliflozin significantly reduced hospitalizations [RR = 0.51, CI (0.33-0.80)], CV death [RR = 0.73, CI (0.54-0.97)], and all-cause mortality [RR = 0.69, CI (0.48-0.99)] in patients with HF with reduced ejection fraction (HFrEF). SGLT2i also plays a significant role in improving cardiac remodeling and quality of life (LVMi, LVEDV, KCQQ) (P < 0.05). Among patients with HF with preserved ejection fraction (HFpEF), SGLT2i significantly improved cardiac function in HFpEF patients (P < 0.05). In addition, canagliflozin [RR = 0.09, CI (0.01-0.86)] demonstrated greater safety compared to sotagliflozin in a composite of urinary and reproductive infections of HFpEF patients. Conclusion: Our systematic review showed that SGLT2i generally enhances the prognosis of patients with HF. Sotagliflozin demonstrated superiority over empagliflozin and dapagliflozin in a composite of hospitalization for HF and CV death in the overall HF patients. Canagliflozin exhibited greater safety compared to sotagliflozin in a composite of urinary and reproductive infections of HFpEF. Overall, the efficacy of SGLT2i was greater in HFrEF patients than in HFpEF patients.
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Key Clinical Message: Linezolid (LZD) is an efficient addition antibiotic against multidrug-resistant strains. However, clinicians should pay attention to the adverse reactions such as hypoglycemia and anemia in using LZD, especially in elderly patients and patients with abnormal liver and kidney function who need to use LZD for a long time. Abstract: Severe hypoglycemia and anemia caused by linezolid (LZD) are rare, with potentially serious adverse effects. The report of LZD-induced hypoglycemia and anemia is extremely rare. Thus far, this is the first report. We presented LZD-induced recurrent hypoglycemia and anemia in a 93-year-old patient who has been prescribed LZD 600 mg once daily for 42 days for treatment of tuberculosis (TB) pleurisy and pneumonia. The patient began to experience recurrent hypoglycemic episodes and anemia 5 days and 2 weeks after LZD medication, respectively. Using Naranjo's Adverse Drug Reaction Assessment Scale, the patient scored 8 points with the category of "probable". His hypoglycemia and anemia gradually improved 1 month after LZD withdrawal. Clinicians should pay attention to the adverse reactions such as hypoglycemia and anemia in using LZD, especially in elderly patients and patients with abnormal liver and kidney function who need to use LZD for a long time. Patients should regularly monitor blood routine, blood glucose, and liver and kidney functions during LZD exposure, which may avoid adverse reactions and improve their prognosis.
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INTRODUCTION: There is no consensus on whether cardiopulmonary reserve affects the risk of gravity-induced loss of consciousness (G-LOC) or almost loss of consciousness (A-LOC). Few previous studies have used cardiopulmonary exercise testing (CPET) to assess cardiopulmonary reserve function (CPRF) of fighter aviators. We compared CPET-related parameters in G-LOC/A-LOC and non-G-LOC/A-LOC fighter aviators to explore the effect of cardiopulmonary reserve function on G tolerance.METHODS: A total of 264 male fighter aviators with more than 500 h of flight experience participated in the study, all of whom underwent CPET and human centrifuge testing. We divided the aviators into two groups based on whether they experienced G-LOC/A-LOC during the human centrifuge test and compared the CPET parameters between the two groups.RESULTS: A total of 37 aviators (14%) experienced G-LOC/A-LOC. There were no significant differences in age (26.65 ± 4.30 vs. 26.01 ± 4.95), height (173.68 ± 4.21 vs. 173.55 ± 3.37), weight (69.51 ± 6.22 vs. 69.63 ± 6.01), or body mass index (23.06 ± 2.11 vs. 23.11 ± 1.82) between the two groups. Forced vital capacity (FVC) (4.95 ± 0.87 vs. 4.65 ± 0.79) and forced expiratory volume in 1 s (FEV1) divided by FVC (FEV1/FVC) (79.88 ± 7.24 vs. 83.72 ± 9.24) of pulmonary function of the G-LOC/A-LOC group was significantly lower than that of the non-G-LOC/A-LOC group. There was no significant difference in CPET-related parameters between the two groups.DISCUSSION: In conclusion, FEV1/FVC may be a factor affecting aviators' G-LOC/A-LOC, meaning aviators with slightly lower ventilation are more likely to experience G-LOC/A-LOC. However, oxygen uptake and exercise blood pressure, oxygen pulse, etc., may not be the main factors influencing G-LOC/A-LOC.Lan X, Zhu W, Du J, Wang J, Yang M, Xu Y, Cao Y. High G tolerance and cardiopulmonary reserve function in healthy air force aviators. Aerosp Med Hum Perform. 2023; 94(12):911-916.
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Pilotos , Humanos , Masculino , Pulmón , Prueba de Esfuerzo , Inconsciencia , Oxígeno , Tolerancia al Ejercicio/fisiologíaRESUMEN
The number of centenarians with cancer is increasing as the global population ages. The diagnosis and treatment for centenarians with tumor sometimes are specific, and there are currently less appropriate guidelines as references. We report a 104-year-old man with asymptomatic primary liver cancer (PLC) whose family decided to receive conservative and palliative care. The patient has been followed up for 27 months. He has been mainly received Chinese herbal medicine (CHM), nutritional support and thymalfasin injection intermittently, etc. During the 27-month follow-up, the patient has showed good compliance and tolerance without any complications of the tumor. Conclusion: Individualized palliative care and complementary medicine, based on multidisciplinary evaluation, traditional Chinese medicine, consultation with patients and their families about treatment options, etc., may help improve the life quality of centenarians with end-stage tumors.
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Background: Although surgical methods are the most effective treatments for colon adenocarcinoma (COAD), the cure rates remain low, and recurrence rates remain high. Furthermore, platelet adhesion-related genes are gaining attention as potential regulators of tumorigenesis. Therefore, identifying the mechanisms responsible for the regulation of these genes in patients with COAD has become important. The present study aims to investigate the underlying mechanisms of platelet adhesion-related genes in COAD patients. Methods: The present study was an experimental study. Initially, the effects of platelet number and related genomic alteration on survival were explored using real-world data and the cBioPortal database, respectively. Then, the differentially expressed platelet adhesion-related genes of COAD were analyzed using the TCGA database, and patients were further classified by employing the non-negative matrix factorization (NMF) analysis method. Afterward, some of the clinical and expression characteristics were analyzed between clusters. Finally, least absolute shrinkage and selection operator regression analysis was used to establish the prognostic nomogram. All data analyses were performed using the R package. Results: High platelet counts are associated with worse survival in real-world patients, and alternations to platelet adhesion-related genes have resulted in poorer prognoses, based on online data. Based on platelet adhesion-related genes, patients with COAD were classified into two clusters by NMF-based clustering analysis. Cluster2 had a better overall survival, when compared to Cluster1. The gene copy number and enrichment analysis results revealed that two pathways were differentially enriched. In addition, the differentially expressed genes between these two clusters were enriched for POU6F1 in the transcription factor signaling pathway, and for MATN3 in the ceRNA network. Finally, a prognostic nomogram, which included the ALOX12 and ACTG1 genes, was established based on the platelet adhesion-related genes, with a concordance (C) index of 0.879 (0.848-0.910). Conclusion: The mRNA expression-based NMF was used to reveal the potential role of platelet adhesion-related genes in COAD. The series of experiments revealed the feasibility of targeting platelet adhesion-associated gene therapy.