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BACKGROUND: The controlled nutritional status score (CONUT) and handgrip strength (HGS) were both predictive indexes for the prognosis of cancers. However, the combination of CONUT and HGS for predicting the prognosis of gastrointestinal cancer had not been developed. This study aimed to explore the combination of CONUT and HGS as the potential predictive prognosis in patients with gastric and colorectal cancer. METHODS: A cohort study was conducted with gastric and colorectal cancer patients in multicenter in China. Based on the optimal HGS cutoff value for different sex, the HGS cutoff value was determined. The patients were divided into high and low HGS groups based on their HGS scores. A CONUT score of 4 or less was defined as a low CONUT, whereas scores higher than 4 were defined as high CONUT. The Kaplan-Meier method was used to create survival curves, and the log-rank test was used to compare time-event relationships between groups. A Cox proportional hazard regression model was used to determine independent risk factors for overall survival (OS). RESULTS: A total 2177 gastric and colorectal patients were enrolled in this study, in which 1391 (63.9%) were men (mean [SD] age, 66.11 [11.60] years). Multivariate analysis revealed that patients with high HGS had a lower risk of death than those with low HGS (hazard ratio [HR],0.87; 95% confidence interval [CI], 0.753-1.006, P = 0.06), while high CONUT had a higher risk of death than those with low CONUT (HR, 1.476; 95% CI, 1.227-1.777, P < 0.001). Patients with both low HGS and high CONUT had 1.712 fold increased risk of death (HR, 1.712; 95% CI, 1.364-2.15, P < 0.001). Moreover, cancer type and sex were stratified and found that patients with high CONUT and low HGS had lower survival rate than those with low CONUT and high HGS in both gastric or colorectal cancer, and both male and female. CONCLUSION: A combination of low HGS and high CONUT was associated with poor prognosis in patients with gastrointestinal cancer, which could probably predict the prognosis of gastrointestinal cancer more accurate than HGS or CONUT alone.
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The gut microbiota is an integral component of the colorectal cancer (CRC) microenvironment and is intimately associated with CRC initiation, progression, and therapeutic outcomes. We reviewed recent advancements in utilizing nanotechnology for modulating gut microbiota, discussing strategies and the mechanisms underlying their design. For future nanomedicine design, we propose a 5I principle for individualized nanomedicine in CRC management.
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BACKGROUND: The presence of frailty decreases the overall survival of cancer patients. An accurate and operational diagnostic method is needed to help clinicians choose the most appropriate treatment to improve patient outcomes. METHODS: Data were collected from 10 649 cancer patients who were prospectively enrolled in the Investigation on Nutritional Status and its Clinical Outcomes of Common Cancers (INSCOC) project in China from July 2013 to August 2022. The training cohort and validation cohort were randomly divided at a ratio of 7:3. The multivariable logistic regression analysis, multivariate Cox regression analyses, and the least absolute shrinkage and selection operator (LASSO) method were used to develop the nomogram. The concordance index and calibration curve were used to assess the diagnostic utility of the nomogram model. RESULTS: The 10 risk factors associated with frailty in cancer patients were age, AJCC stage, liver cancer, hemoglobin, radiotherapy, surgery, hand grip strength (HGS), calf circumference (CC), PG-SGA score and QOL from the QLQ-C30. The diagnostic nomogram model achieved a good C index of 0.847 (95% CI, 0.832-0.862, P < 0.001) in the training cohort and 0.853 (95% CI, 0.83-0.876, P < 0.001) in the validation cohort. The prediction nomogram showed 1-, 3-, and 5-year mortality C indices in the training cohort of 0.708 (95% CI, 0.686-0.731), 0.655 (95% CI, 0.627-0.683), and 0.623 (95% CI, 0.568-0.678). The 1-, 3-, and 5-year C indices in the validation cohort were similarly 0.743 (95% CI, 0.711-0.777), 0.680 (95% CI, 0.639-0.722), and 0.629 (95% CI, 0.558-0.700). In addition, the calibration curves and decision curve analysis (DCA) were well-fitted for both the diagnostic model and prediction model. CONCLUSIONS: The nomogram model provides an accurate method to diagnose frailty in cancer patients. Using this model could lead to the selection of more appropriate therapy and a better prognosis for cancer patients.
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BACKGROUND: Aging is an inevitable biological process. Accelerated aging renders adults more susceptible to chronic diseases and increases their mortality rates. Previous studies have reported the relationship between lifestyle factors and phenotypic aging. However, the relationship between intrinsic factors, such as reproductive factors, and phenotypic aging remains unclear. METHODS: This study utilized data from the National Health and Nutrition Examination Survey (NHANES), spanning from 1999 to 2010 and 2015-2018, with 14,736 adult women. Random forest imputation was used to handle missing covariate values in the final cohort. Weighted linear regression was utilized to analyze the relationship between women-specific reproductive factors and PhenoAgeAccel. Considering the potential impact of menopausal status on the results, additional analyses were conducted on premenopausal and postmenopausal participants. Additionally, the Life's Essential 8 (LE8) was used to investigate the impact of healthy lifestyle and other factors on the relationship between women-specific reproductive factors and PhenoAgeAccel. Stratified analyses were conducted based on significant interaction p-values. RESULTS: In the fully adjusted models, delayed menarche and gynecological surgery were associated with increased PhenoAgeAccel, whereas pregnancy history were associated with a decrease. Additionally, early or late ages of menopause, first live birth, and last live birth can all negatively impact PhenoAgeAccel. The relationship between women-specific reproductive factors and PhenoAgeAccel differs between premenopausal and postmenopausal women. High LE8 scores positively impacted the relationship between certain reproductive factors (age at menarche, age at menopause, age at first live birth, and age at last live birth) and phenotypic age acceleration. Stratified analysis showed significant interactions for the following variables: BMI with age at menarche, pregnancy history, and age at menopause; ethnicity with age at menopause, age at first live birth, and parity; smoking status with use of contraceptive pills and gynecologic surgery; hypertension with use of contraceptive pills, pregnancy history, and age at menopause. CONCLUSION: Delayed menarche, gynecological surgery, and early or late ages of menopause, first live birth, and last live birth are associated with accelerated phenotypic aging. High LE8 score may alleviate the adverse effects of reproductive factors on phenotypic aging.
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Envelhecimento , Menarca , Menopausa , Inquéritos Nutricionais , Fenótipo , Humanos , Feminino , Adulto , Envelhecimento/fisiologia , Pessoa de Meia-Idade , Inquéritos Nutricionais/estatística & dados numéricos , Inquéritos Nutricionais/métodos , Menopausa/fisiologia , Menarca/fisiologia , Gravidez , Idoso , Reprodução/fisiologia , História Reprodutiva , Estilo de VidaRESUMO
OBJECTIVE: This study aimed to define the calf proportion index (CPI) and investigate its association with malnutrition and survival in overweight and obese patients with cancer. METHODS: This multicenter observational cohort study included 3499 patients diagnosed with cancer, including 3145 overweight and 354 obese individuals. The CPI was defined as the ratio of the cross-sectional area of the calf circumference (CC) to the body surface area (BSA). A CPI calculator that automatically calculated the CPI and survival probability based on the patient's sex, height, weight, and CC was developed. RESULTS: During a median follow-up of 44.1 months, 935 deaths were recorded. Receiver operating characteristic curves revealed that the CPI was better than CC and BSA as a predictor of survival, with AUCs for the 3-year mortality rate were 0.574, 0.553 and 0.529, respectively. In overweight and obese patients with cancer, the optimal CPI cut-off value was 0.65 % for men and 0.57 % for women. The Kaplan-Meier curve revealed that patients with a low CPI had lower survival. After adjusting confounding factors, a low CPI was an independent risk factor for overweight (hazard ratio [HR]: 1.29, 95 % confidence interval [CI]: 1.11-1.51, P < 0.001) and obesity (HR: 1.92, 95 % CI: 1.20-3.09, P = 0.007) in patients with cancer. The CPI exhibited significant prognostic value in patients with lung and digestive system cancers. The risk of malnutrition was significantly higher in patients with a low CPI (HR: 1.25, 95 % CI: 1.04-1.50, P = 0.019). CONCLUSIONS: The CPI is a useful prognostic indicator in overweight and obese patients with cancer, especially in obese patients.
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Background: Diet quality significantly influences aging processes and age-related health outcomes. This study aims to explore the association between dietary quality and accelerated aging in two large cohorts. Methods: This study collected data from the Kailuan and National Health and Nutrition Examination Survey (NHANES) cohorts; participants' dietary quality was evaluated using the American Heart Association (AHA) dietary score and Healthy Eating Index-2015 (HEI-2015), respectively. Accelerated aging in participants was determined by calculating the difference between phenotypic age and chronological age. Logistic regression models were used to explore the association between dietary quality scores and accelerated aging. Additionally, variations in this association across different subgroups were investigated. To minimize the influence of excessive aging, individuals aged 75 and above were excluded in sensitivity analyses. Results: In this study, we included 33 701 participants (27.3% female, mean age 57.29 ± 11.88) from the Kailuan study and 9285 participants (50.6% female, mean age 49.83 ± 17.62) from NHANES. In the Kailuan cohort, individuals with dietary scores ranging from 3 to 5 exhibited a 22% lower risk of accelerated aging compared to those scoring between 0 and 2 (OR = 0.78, 95% CI = 0.72-0.85). Similarly, in the NHANES cohort, participants in the highest quartile of HEI-2015 experienced a 34% reduction in the risk of accelerated aging compared to those in the lowest quartile (OR = 0.66, 95% CI = 0.52-0.84). Subgroup analyses underscored a more pronounced association between dietary quality and accelerated aging among males and individuals with unhealthy lifestyles. Sensitivity analyses confirmed the robustness of the association between dietary quality and accelerated aging. Conclusion: In summary, our study found a significant association between dietary quality and accelerated aging. Better dietary quality was associated with a reduced risk of accelerated aging, particularly among males, smokers, and participants with unhealthy lifestyles.
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Envelhecimento , Dieta , Inquéritos Nutricionais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Idoso , Estudos de Coortes , Adulto , Dieta Saudável , ChinaRESUMO
BACKGROUND: Inflammatory factors have increasingly become a more cost-effective prognostic indicator for gastric cancer (GC). The goal of this study was to develop a prognostic score system for gastric cancer patients based on inflammatory indicators. METHODS: Patients' baseline characteristics and anthropometric measures were used as predictors, and independently screened by multiple machine learning(ML) algorithms. We constructed risk scores to predict overall survival in the training cohort and tested risk scores in the validation. The predictors selected by the model were used in multivariate Cox regression analysis and developed a nomogram to predict the individual survival of GC patients. RESULTS: A 13-variable adaptive boost machine (ADA) model mainly comprising tumor stage and inflammation indices was selected in a wide variety of machine learning models. The ADA model performed well in predicting survival in the validation set (AUC = 0.751; 95% CI: 0.698, 0.803). Patients in the study were split into two sets - "high-risk" and "low-risk" based on 0.42, the cut-off value of the risk score. We plotted the survival curves using Kaplan-Meier analysis. CONCLUSION: The proposed model performed well in predicting the prognosis of GC patients and could help clinicians apply management strategies for better prognostic outcomes for patients.
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Biomarcadores Tumorais , Nomogramas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Feminino , Masculino , Prognóstico , China/epidemiologia , Pessoa de Meia-Idade , Idoso , Inflamação , Aprendizado de Máquina , Estudos de Coortes , Estimativa de Kaplan-Meier , Adulto , Estadiamento de Neoplasias , Modelos de Riscos ProporcionaisRESUMO
Importance: The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) have recently proposed a consensus definition and diagnostic criteria for sarcopenic obesity (SO). Objective: To implement the ESPEN-EASO diagnostic algorithm to investigate the prevalence of SO and its association with outcomes in patients with solid tumor cancers, with particular regard to associations among SO, overall survival (OS), and patient quality of life (QoL). Design, Setting, and Participants: This prospective cohort study included patients diagnosed with solid tumor starting in May 7, 2013, with the last follow-up on June 30, 2022. Patients with solid tumors were categorized into SO and non-SO groups according to ESPEN-EASO criteria. The primary outcome was OS and the secondary outcomes included patient QoL and risk of intensive care unit (ICU) admission. Data were analyzed from June to December 2023. Results: A total of 6790 patients were included in the study (mean [SD] age, 59.64 [10.77] years; 3489 were female [51.4%]). The prevalence of SO was 4.36% (296 of 6790) in the whole cohort and 14.98% (296 of 1976) in the subgroup with obesity. SO prevalence increased with age. During a median (IQR) follow-up period of 6.83 (5.67-7.04) years, 2103 patients died. Cox regression analysis indicated that SO was independently associated with lower OS (hazard ratio [HR], 1.54; 95% CI, 1.23-1.92), which was observed in both men (HR, 1.51; 95% CI, 1.09-2.10) and women (HR, 1.53; 95% CI, 1.12-2.07). SO was also associated with poorer QoL and higher risk of ICU admission (odds ratio, 2.39; 95% CI, 1.06-5.29). Among the diagnostic components of SO, low hand grip strength (HGS) was the only SO component associated with poor OS (HR, 1.15; 95% CI, 1.04-1.28). Conclusions and Relevance: This cohort study of SO found that SO was significantly associated with lower OS, poorer QoL, and higher risk of ICU admission. Weak HGS, 1 of the diagnostic conditions, was the only component of SO associated with OS. The ESPEN-EASO algorithm appears to be an applicable tool to identify cancer-associated SO, which represents a major clinical complication and factor associated with risk for poor outcomes in these patients.
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Neoplasias , Obesidade , Qualidade de Vida , Sarcopenia , Humanos , Masculino , Feminino , Neoplasias/epidemiologia , Neoplasias/mortalidade , Neoplasias/complicações , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/complicações , Sarcopenia/epidemiologia , Estudos Prospectivos , Idoso , PrevalênciaRESUMO
BACKGROUND: Reduced muscle mass is a criterion for diagnosing malnutrition using the Global Leadership Initiative on Malnutrition (GLIM) criteria; however, the choice of muscle-mass indicators within the GLIM criteria remains contentious. This study aimed to establish muscle-measurement-based GLIM criteria using data from bio-electrical impedance analysis (BIA) and anthropometric evaluations and evaluate their ability to predict overall survival (OS), short-term outcomes, and healthcare burden in patients with cancer. METHODS: This was a multicenter, prospective study that commenced in 2013 and enrolled participants from various clinical centers across China. We constructed GLIM criteria based on various muscle measurements, including fat-free mass index (FFMI), skeletal muscle index (SMI), calf circumference (CC), midarm circumference (MAC), midarm muscle circumference (MAMC), and midarm muscle area (MAMA). Survival was estimated using the Kaplan-Meier method and survival curves were compared using the log-rank test. Cox proportional hazards regression was used to assess the independent association between the GLIM criteria and OS. The discriminatory performance of different muscle-measurement-based GLIM criteria for mortality was evaluated using Harrell's concordance index (C-index). Logistic regression was used to evaluate the association of the GLIM criteria with short-term outcomes and healthcare burden. RESULTS: A total of 4769 patients were included in the analysis, of whom 1659 (34.8%) died during the study period. The Kaplan-Meier curves demonstrated that all muscle-measurement-based GLIM criteria significantly predicted survival in patients with cancer (all p < 0.001). The survival rate of malnourished patients was approximately 10% lower than that of non-malnourished patients. Cox proportional hazards regression showed that all the muscle-measurement-based GLIM could independently predict the OS of patients (all p < 0.001). The prognostic discrimination was as follows: MAMC (Chi-square: 79.61) > MAMA (Chi-square: 79.10) > MAC (Chi-square: 64.09) > FFMI (Chi-square: 62.33) > CC (Chi-square: 58.62) > ASMI (Chi-square: 57.29). In comparison to the FFMI-based GLIM criteria, the ASMI-based criteria (-0.002, 95% CI: -0.006 to 0.002, p = 0.334) and CC-based criteria (-0.003, 95% CI: -0.007 to 0.002, p = 0.227) did not exhibit a significant advantage. However, the MAC-based criteria (0.001, 95% CI: -0.003 to 0.004, p = 0.776), MAMA-based criteria (0.004, 95% CI: 0.000-0.007, p = 0.035), and MAMC-based criteria (0.005, 95% CI: 0.000-0.007, p = 0.030) outperformed the FFMI-based GLIM criteria. Logistic regression showed that muscle measurement-based GLIM criteria predicted short-term outcomes and length of hospital stay in patients with cancer. CONCLUSION: All muscle measurement-based GLIM criteria can effectively predict OS, short-term outcomes, and healthcare burden in patients with cancer. Anthropometric measurement-based GLIM criteria have potential for clinical application as an alternative to BIA-based measurement.
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Antropometria , Impedância Elétrica , Desnutrição , Músculo Esquelético , Neoplasias , Humanos , Masculino , Feminino , Desnutrição/diagnóstico , Desnutrição/mortalidade , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias/mortalidade , Neoplasias/diagnóstico , Prognóstico , Antropometria/métodos , Músculo Esquelético/fisiopatologia , Idoso , China/epidemiologia , Composição Corporal , Avaliação Nutricional , Adulto , Estado NutricionalRESUMO
BACKGROUND AND AIMS: The impact of lipids on the overall survival (OS) of patients with malignancy has not yet been clarified. This study aimed to evaluate the effect of hyperlipidemia on the OS among Chinese patients based on Body Mass Index (BMI) stratifications and hyperlipidemia types. METHOD: The patients in this study were derived from the Investigation of the Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) trial. Kaplan-Meier was used to draw the survival curve, and the log-rank test was used to estimate the survival rates between each group. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: A total of 9054 patients were included in the final study, with a median age of 59 years, and 55.3% (5004) of them were males. Regarding types of hyperlipidemia, only low high-density lipoprotein was an independent risk factor for the prognosis of all patients (HR = 1.35, 95% CI: 1.25-1.45, P < 0.001), while high total cholesterol (HR = 1.01, 95% CI: 0.90-1.15, P = 0.839) and high low-density lipoprotein (HR = 1.03, 95%CI: 0.91-1.16, P = 0.680) were not. In terms of BMI stratification, the effect of triglycerides on prognosis varied; high triglycerides were an independent risk factor for the prognosis of underweight patients (HR = 1.56, 95% CI:1.05-2.32, P = 0.027) and a protective factor for overweight patients (HR = 0.75, 95% CI: 0.63-0.89, P = 0.001). However, for normal-weight patients, there was no significant statistical difference (HR = 0.88, 95%CI: 0.75-1.03, P = 0.108). CONCLUSIONS: The impact of hyperlipidemia on the OS among patients with cancer varied by different BMI and hyperlipidemia types. BMI and hyperlipidemia type ought to be considered in combination to estimate the prognosis of patients with malignancy.
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This study explores the potential role and mechanism of Ginsenoside Rb3 (Rb3) in modulating osteoclastogenesis induced by human periodontal ligament fibroblasts (hPLFs) within the periodontitis microenvironment. We investigated the anti-inflammatory effects of Rb3 on hPLFs stimulated with Porphyromonas gingivalis lipopolysaccharide (P.g-LPS) utilizing quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay techniques. Moreover, the functional role of Rb3 in hPLFs-induced osteoclast formation was assessed by treating human bone marrow-derived macrophages (hBMMs) with conditioned medium from hPLFs, followed by analyses through qPCR, western blot analysis, and staining for tartrate-resistant acid phosphatase (TRAP) and phalloidin. The impact of Rb3 on the activation of the STAT3 signaling pathway was determined via western blot analysis. Results indicated that Rb3 treatment significantly suppressed the upregulation of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, MCP-1, and IL-18) at both gene and protein levels in hPLFs induced by P.g-LPS. Furthermore, conditioned medium from Rb3 plus P.g-LPS treated hPLFs notably decreased the number of TRAP-positive cells, actin ring formations, and the expression of osteoclast marker genes (including CTSK, NFATC1, and ACP5). Rb3 also inhibited the P.g-LPS-induced activation of the STAT3 pathway, with the activation of STAT3 partially reversing the effects of Rb3 on inflammation and osteoclast differentiation. Collectively, Rb3 ameliorates inflammation in P.g-LPS-stimulated hPLFs and reduces hPLFs-induced osteoclastogenesis by inhibiting the STAT3 signaling pathway, suggesting its potential as a therapeutic agent for periodontitis.
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Fibroblastos , Ginsenosídeos , Osteoclastos , Ligamento Periodontal , Periodontite , Fator de Transcrição STAT3 , Transdução de Sinais , Fator de Transcrição STAT3/metabolismo , Ginsenosídeos/farmacologia , Humanos , Fibroblastos/metabolismo , Fibroblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Ligamento Periodontal/citologia , Ligamento Periodontal/metabolismo , Ligamento Periodontal/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Periodontite/metabolismo , Periodontite/tratamento farmacológico , Células Cultivadas , Osteogênese/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Porphyromonas gingivalis , Microambiente Celular/efeitos dos fármacos , Citocinas/metabolismo , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacosRESUMO
Introduction: Malnutrition is prevalent among individuals with gastric cancer and notably decreases their quality of life (QOL). However, the factors impacting QOL are yet to be clearly defined. This study aimed to identify essential factors impacting QOL in malnourished patients suffering from gastric cancer. Methods: By using the Patient-Generated Subjective Global Assessment (PG-SGA) to assess the nutritional status (≥4 defined malnutrition) of hospitalized cancer patients, 4,586 gastric cancer patients were ultimately defined as malnourished. Spearman method was used to calculate the relationship between clinical features and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Then, univariate and multivariate logistic regression were used to observe which factors affected QOL, and subgroup analysis was performed in young and old population respectively. In addition, we used univariate and multivariate logistic regression to explore whether and how self-reported frequent symptoms in the last 2 weeks of the PG-SGA score affected QOL. Results: In multivariate logistic regression analysis of clinical features of patients with malnourished gastric cancer, women, stage II, stage IV, WL had an independent correlation with a low global QOL scores. However, BMI, secondary education, higher education, surgery, chemotherapy, HGS had an independent correlation with a high global QOL scores. In multivariate logistic regression analysis of symptoms in self-reported PG-SGA scores in patients with malnourished gastric cancer, having no problem eating had an independent correlation with a high global QOL scores. However, they have no appetite, nausea, vomiting, constipation and pain had an independent correlation with a lower global QOL scores. The p values of the above statistical results are both < 0.05. Conclusion: This study demonstrates that QOL in malnourished patients with gastric cancer is determined by female sex, stage II, stage IV, BMI, secondary and higher education or above, surgery, chemotherapy, WL, and HGS. Patients' self-reported symptoms of nearly 2 weeks, obtained by using PG-SGA, are also further predictive of malnourished gastric cancer patients. Detecting preliminary indicators of low QOL could aid in identifying patients who might benefit from an early referral to palliative care and assisted nursing.
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This study aimed to develop a clinically applicable inflammaging score by combining the inflammatory status and age of patients. Kaplan-Meier analysis was used to compare survival differences among patients with different grades of inflammation scores. Cox proportional hazard regression analysis was used to explore the relationship between the inflammaging score and survival. As the age of patients increased, their levels of systemic inflammation gradually increased. A unique inverse relationship was found between the level of inflammation and cancer prognosis during the ageing process. Mediation analysis indicated that systemic inflammation mediates 10.1%-17.8% of the association between ageing and poor prognosis. With an increase in the inflammaging score from grades I to V, the survival rate showed a gradient decline. The inflammation score could effectively stratify the prognosis of patients with lung, bronchial, gastrointestinal, and other types of cancers. Compared with grade I, the hazard ratios for grades II-V were 1.239, 1.604, 1.724, and 2.348, respectively. In the external validation cohort, the inflammaging score remained an independent factor affecting the prognosis of patients with cancer. The inflammaging score, which combines ageing and inflammation, is a robust prognostic assessment tool for cancer patients.
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Envelhecimento , Inflamação , Neoplasias , Humanos , Feminino , Masculino , Neoplasias/mortalidade , Pessoa de Meia-Idade , Idoso , Prognóstico , Estudos de Coortes , Adulto , Estimativa de Kaplan-Meier , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Anthropometric indicators have been shown to be associated with the prognosis of patients with cancer. However, any single anthropometric index has limitation in predicting the prognosis. OBJECTIVES: This study aimed to observe the predictive role of 7 anthropometric indicators based on body size on the prognosis of patients with cancer. METHODS: A principal component analysis (PCA) on 7 anthropometric measurements: height, weight, BMI, hand grip strength (HGS), triceps skinfold thickness (TSF), mid-upper arm circumference (MAC), and calf circumference (CAC) was conducted. Principal components (PCs) were derived from this analysis. Cox regression analysis was used to investigate the association between the prognosis of patients with cancer and the PCs. Subgroups and sensitivity analyses were also conducted. RESULTS: Through PCA, 4 distinct PCs were identified, collectively explaining 88.3% of the variance. PC1, primarily characterized by general obesity, exhibited a significant inverse association with risk of cancer-related death (adjusted hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.83, 0.88). PC2 (short stature with high TSF) was not significantly associated with cancer prognosis. PC3 (high BMI coupled with low HGS) demonstrated a significant increase with risk of cancer-related death (adjusted HR: 1.08; 95% CI: 1.05, 1.11). PC4 (tall stature with high TSF) exhibited a significant association with increased cancer risk (adjusted HR: 1.05; 95% CI: 1.02, 1.07). These associations varied across different cancer stages. The stability of the results was confirmed through sensitivity analyses. CONCLUSIONS: Different body sizes are associated with distinct prognostic outcomes in patients with cancer. The impact of BMI on prognosis is influenced by both HGS and subcutaneous fat. This finding may influence the clinical care of cancer and improve the survival of cancer patients.
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Antropometria , Neoplasias , Humanos , Masculino , Feminino , Neoplasias/mortalidade , Prognóstico , Pessoa de Meia-Idade , Estudos de Coortes , Índice de Massa Corporal , Idoso , Adulto , Força da Mão , Análise de Componente PrincipalRESUMO
The characteristics of early-onset (onset age <50 years) and later-onset (onset age â½ 50 years) cancers differ significantly. Identifying novel risk factors for both types of cancer is crucial for increasing awareness of cancer prevention and for reducing its burden. This study aimed to analyze the trends in incidence and risk factors for early-onset and late-onset cancers. We conducted a prospective study by drawing data from the Kailuan Study. This study included 6,741 participants with cancer (624 with early-onset cancer and 6,117 with later-onset cancer) and 6,780 matched controls among the 186,249 participants who underwent Kailuan health examinations from 2006 to 2019. The primary outcomes were cancer incidence rates, and associated risk factors for early- and later-onset cancer. Weighted Cox regression was used to calculate hazard ratios and 95% confidence intervals of each exposure factor for early- and later-onset cancer by cancer type. Population-attributable risk proportions were used to estimate the number of cases that could be prevented by eliminating a risk factor from the population. Except for liver cancer, incidence rates for nearly all types of cancer increased during the study period. Smoking, alcohol consumption, lipid metabolism disorders, hypertension, diabetes mellitus, fatty liver, and inflammation were associated with a significantly increased risk of cancer at multiple sites, but risk factors for cancer incidence differed by site. Smoking, alcohol consumption, inflammation, and hypertension were the major contributors to preventable cancer. The incidence of several different types of cancer, including early-onset cancer, is increasing in northeastern China. Differences in risk factors between early-onset and later-onset malignancies may contribute to the divergence in the observed changes in incidence trends between these two specific types of cancer.
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BACKGROUND: This study aimed to investigate the regulatory mechanism of the adipose factor interleukin (IL)-6 in promoting pentraxin 3 (PTX3) expression in triple-negative breast cancer (TNBC). METHODS: We established an in vitro coculture model of mature adipocytes and TNBC cells using a Transwell system. Cell scratch, Transwell migration, and matrix invasion assays were used to evaluate the migration and invasion abilities of TNBC cells cocultured with adipocytes. Next, we used lentivirus-mediated functional depletion experiments to study PTX3's role in the adipocyte-dependent migration of TNBC cells. RESULTS: After coculturing TNBC cells with adipocytes, PTX3 expression was upregulated, which accompanied enhanced cell migration and invasion. Using GEO data and RNA-seq analysis, we identified PTX3 as a key target gene influenced by the adipose TNBC microenvironment. IL-6 upregulation in the conditioned medium of mature adipocytes and in the serum of high-fat diet mice was associated with this effect, and the recombinant protein IL-6 significantly promoted the migration and invasion of TNBC cells along with the phosphorylation of intracellular STAT3 and the upregulation of PTX3. PTX3 knockdown inhibited TNBC cell migration and eliminated the enhanced migration caused by coculturing with adipocytes. Furthermore, in vivo experiments confirmed that the PTX3 knockdown reduced obesity-induced lung metastasis. Subsequent experiments with cytokines and drug inhibitors confirmed that adipocyte-derived IL-6 promoted PTX3 expression by activating the STAT3 signaling pathway. Additionally, bioinformatic analysis indicated that PTX3 promotes TNBC metastasis by regulating the matrix metalloproteinase (MMP) family. CONCLUSION: Our study elucidated Obesity-related metabolic inflammation promotes the progression via the IL-6/STAT3/PTX3/MMP7 axis.
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Proteína C-Reativa , Movimento Celular , Interleucina-6 , Obesidade , Fator de Transcrição STAT3 , Componente Amiloide P Sérico , Neoplasias de Mama Triplo Negativas , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Animais , Interleucina-6/metabolismo , Interleucina-6/genética , Componente Amiloide P Sérico/metabolismo , Componente Amiloide P Sérico/genética , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Humanos , Feminino , Obesidade/metabolismo , Camundongos , Proteína C-Reativa/metabolismo , Proteína C-Reativa/genética , Linhagem Celular Tumoral , Transdução de Sinais , Progressão da Doença , Adipócitos/metabolismo , Inflamação/metabolismo , Técnicas de Cocultura , Camundongos Endogâmicos C57BL , Regulação Neoplásica da Expressão GênicaRESUMO
OBJECTIVES: The aim of this study was to investigate the relationship among phase angle (PA), malnutrition, and prognosis in patients with gastrointestinal cancer. METHODS: In total, 870 patients with gastrointestinal cancer were enrolled. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate the association between PA and survival risk. Restricted cubic spline regression was used for flexibility analysis to explore sex-specific associations between PA and survival. Logistic regression was used to assess the relationships among PA, malnutrition, and cachexia. RESULTS: Low PA was closely associated with poor physical conditions, diminished quality of life, and malnutrition. Patients with low PA had a significantly worse prognosis than those with high PA (60.6% versus 72.8%; log-rank P < 0.001). PA was suitable for the prognostic assessment of patients with advanced-stage tumors. Regardless of sex, patients with lower PA showed significantly poorer survival rates. Cox proportional hazards models identified PA as an independent predictor of prognosis in patients with gastrointestinal cancer (hazard ratio (HR)=0.534; 95% confidence interval (CI)=0.409-0.696, P < 0.001). Subgroup analysis indicated that a high PA was an independent risk factor affecting the prognoses of patients with esophageal, liver, and intrahepatic bile duct cancers. Interestingly, variations in PA had a more significant prognostic effect on survival in men than in women. The logistic regression model confirmed that PA is a valuable indicator for assessing malnutrition and cachexia in patients with gastrointestinal cancer. Among all body composition indicators, PA demonstrated the highest accuracy for prognostic prediction. CONCLUSIONS: PA was identified as a robust predictor of malnutrition and poor prognosis in patients with gastrointestinal cancer.
Assuntos
Caquexia , Neoplasias Gastrointestinais , Desnutrição , Humanos , Masculino , Feminino , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/mortalidade , Desnutrição/diagnóstico , Prognóstico , Pessoa de Meia-Idade , Caquexia/etiologia , Caquexia/mortalidade , Idoso , Modelos de Riscos Proporcionais , Fatores de Risco , Estimativa de Kaplan-Meier , Qualidade de Vida , Estado Nutricional , Avaliação NutricionalRESUMO
The C677T polymorphism in the MTHFR gene and its role in folate metabolism, impacting serum folate metabolites like THF and 5-MTHF, is a critical but underexplored area in cancer research. This nested case-control study utilized data from CHHRS, involving 87,492 hypertensive adults without prior cancer. During a median of 2.02 years, we identified 1332 cancer cases and matched controls based on age, sex, and residency. Serum levels of folate, THF, and 5-MTHF were measured, and the MTHFR C677T gene polymorphism was considered. Statistical analyses included restricted cubic spline regression and conditional logistic regression models. Serum THF levels were inversely associated with overall cancer risk (ORper SD = 0.90, 95% CI = 0.82-0.99), while 5-MTHF levels showed a negative association in the general cohort (ORQ3 vs. Q1 = 0.76, 95% CI = 0.60-0.96; ORQ4 vs. Q1 = 0.75, 95% CI = 0.58-0.98) and in individuals with MTHFR C677T (CC + CT) polymorphism (ORper SD = 0.87, 95% CI = 0.77-0.99; ORQ4 VS. Q1 = 0.79, 95% CI = 0.61-0.98), but a positive association in the MTHFR C677T (TT) subgroup (ORper SD = 1.89, 95% CI = 1.02-3.72; ORQ4 VS. Q1 = 2.17, 95% CI = 1.06-8.21). The impact of folate, THF, and 5-MTHF on cancer risk varied significantly across different cancer types and MTHFR C677T genotypes. This study provides novel insights into the variable effects of folate and its metabolites on cancer risk, influenced by genetic factors like the MTHFR C677T polymorphism and cancer type.
Assuntos
Ácido Fólico , Metilenotetra-Hidrofolato Redutase (NADPH2) , Neoplasias , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Ácido Fólico/sangue , Ácido Fólico/metabolismo , Feminino , Neoplasias/genética , Neoplasias/epidemiologia , Masculino , Estudos de Casos e Controles , Pessoa de Meia-Idade , Idoso , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Tetra-Hidrofolatos , Adulto , GenótipoRESUMO
BACKGROUND: Depression is a common psychological disorder worldwide, affecting mental and physical health. Previous studies have explored the benefits of polyunsaturated fatty acids (PUFAs) intake in depressive symptoms; however, few studies have focused on the association between all types of fatty acids intake and depressive symptoms. Therefore, we explored the relationship between the intake of different fatty acids intake and the risk of depressive symptoms. METHODS: The study was based on the data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES), a large US-based database. We used a nutrient residual model and multi-nutrient density model for the analysis. We calculated the nutrient density and residual in men and women separately, and the fatty acids intake was divided into quartiles based on the sex distribution. The relationship between the depressive symptoms and the intake of different fatty acids was examined using logistic regression; furthermore, we explored the relationships separately in men and women. RESULTS: The intake of monounsaturated fatty acids (MUFAs) and PUFAs, particularly n-3 and n-6 PUFAs, were associated with reduced odds ratios for depressive symptoms. The inverse relationship between the intake of MUFAs, PUFAs, n-3, and n-6 PUFAs and depressive symptoms was stronger in women. The inverse relationship between total fatty acid (TFAs) intake and depressive symptoms existed only in a single model. In contrast, saturated fatty acid (SFAs) intake was not related to depressive symptoms. CONCLUSION: Consuming MUFAs and PUFAs can counteract the depressive symptoms, especially in women.
Assuntos
Depressão , Inquéritos Nutricionais , Humanos , Feminino , Masculino , Depressão/epidemiologia , Adulto , Pessoa de Meia-Idade , Ácidos Graxos/administração & dosagem , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Monoinsaturados/administração & dosagem , Estados Unidos/epidemiologia , Ácidos Graxos Insaturados/administração & dosagem , Estudos Transversais , Ácidos Graxos Ômega-6/administração & dosagem , Fatores Sexuais , Adulto Jovem , IdosoRESUMO
CRISPR/Cas9 possesses the most promising prospects as a gene-editing tool in post-genomic researches. It becomes an epoch-marking technique for the features of speed and convenience of genomic modification. However, it is still unclear whether CRISPR/Cas9 gene editing can cause irreversible damage to the genome. In this study, we successfully knocked out the WHITE gene in Drosophila, which governs eye color, utilizing CRISPR/Cas9 technology. Subsequently, we conducted high-throughput sequencing to assess the impact of this editing process on the stability of the entire genomic profile. The results revealed the presence of numerous unexpected mutations in the Drosophila genome, including 630 SNVs (Single Nucleotide Variants), 525 Indels (Insertion and Deletion) and 425 MSIs (microsatellite instability). Although the KO (knockout) specifically occurred on chromosome X, the majority of mutations were observed on chromosome 3, indicating that this effect is genome-wide and associated with the spatial structure between chromosomes, rather than being solely limited to the location of the KO gene. It is worth noting that most of the mutations occurred in the intergenic and intron regions, without exerting any significant on the function or healthy of the animal. In addition, the mutations downstream of the knockout gene well beyond the upstream. This study has found that gene editing can lead to unexpected mutations in the genome, but most of these mutations are harmless. This research has deepened our understanding of CRISPR/Cas9 and broadened its application prospects.