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OBJECTIVES: There is little evidence on the association between low-fat dietary patterns and lung cancer risk among middle-aged and older adults. To fill this gap, we comprehensively investigated the association of adherence to a low-fat diet (LFD) and intake of different fat components including saturated, monounsaturated, and polyunsaturated fatty acids with incidence of lung cancer and its subtypes [non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC)] among adults aged 55 years and older. DESIGN: A prospective cohort study with a mean follow-up time of 8.8 years. SETTING AND PARTICIPANTS: This study used data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The study population included 98,459 PLCO participants age 55 and over at baseline who completed food frequency questionnaires providing detailed dietary information and had no history of cancer. METHODS: Dietary intake was assessed using a validated food frequency questionnaire at baseline. A LFD score was calculated based on fat, protein, and carbohydrate intake as a percentage of total calories. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between LFD score and intake of fat components (in quartiles) and incident lung cancer and its subtypes over follow-up. Restricted cubic spline analyses were conducted to examine possible nonlinear relationships. Subgroup analyses were performed to evaluate potential effect modifiers, and several sensitivity analyses were conducted to assess the stability of the findings. RESULTS: During a follow-up of 869,807.9 person-years, 1,642 cases of lung cancer were observed, consisting of 1,408 (85.75%) cases of NSCLC and 234 (14.25%) cases of SCLC. The highest versus the lowest quartiles of the LFD score were found to be associated with a reduced risk of lung cancer (HR, 0.76; 95% CI, 0.66-0.89), NSCLC (HR, 0.79; 95% CI, 0.67-0.93), and SCLC (HR, 0.59; 95% CI, 0.38-0.92). The restricted cubic spline plots demonstrated a linear dose-response relationship between the LFD score and the risk of lung cancer as well as its subtypes. This risk reduction association for overall lung cancer was more pronounced in smokers (HR, 0.71; 95% CI, 0.60-0.84; P for interaction = 0.003). For fat components, high consumption of saturated fatty acids was associated with an increased lung cancer risk (HR, 1.35; 95% CI, 1.10-1.66), especially for SCLC (HR, 2.05; 95% CI, 1.20-3.53). No significant association was found between consumption of monounsaturated or polyunsaturated fatty acids and incident lung cancer and its subtypes. CONCLUSIONS: Our findings suggest that adherence to LFD may reduce the lung cancer risk, particularly in smokers; while high saturated fatty acids consumption may increase lung cancer risk, especially for SCLC, among middle-aged and older adults in the US population.
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Dieta con Restricción de Grasas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/etiología , Masculino , Estudios Prospectivos , Persona de Mediana Edad , Femenino , Anciano , Factores de Riesgo , Incidencia , Grasas de la Dieta/administración & dosificación , Estados Unidos/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/prevención & control , Estudios de Seguimiento , Carcinoma Pulmonar de Células Pequeñas/epidemiología , Carcinoma Pulmonar de Células Pequeñas/prevención & control , Carcinoma Pulmonar de Células Pequeñas/etiología , Cooperación del Paciente/estadística & datos numéricos , Encuestas y Cuestionarios , Ingestión de Energía , Modelos de Riesgos ProporcionalesRESUMEN
Accumulated evidence implicates lipid peroxidation as a key mechanism contributing to the pathogenesis of lupus nephritis (LN). Ferroptosis is a specialized form of cell death induced by loss or deficient activity of the glutathione peroxidase 4 (GPX4) and decreased clearance of polyunsaturated fatty acid hydroperoxides. STING production may lead to the occurrence of intracellular lipid peroxidation, ultimately triggering ferroptosis, but it has not been clarified whether STING can aggravate LN via ferroptosis. The adjacent normal kidney tissues from renal cell carcinoma and biopsied kidney tissue samples from LN patients were used for research, and the expression of STING protein in kidney tissue was detected by immunohistochemistry and RT-qPCR. MRL/lpr mice, a model of LN, were used to detect STING expression in kidney tissue. STING expression in the kidney tissue of MRL/lpr mice was knocked down by sh-STING-AAV, and then levels of 4-HNE, MDA, ROS, iron ion, blood urea nitrogen and serum creatinine, IL-6, IL-1ß, and TNF-α, and the protein expression of STING, TBK1, NF-κB, GPX4, ACSL4, and SLC7A11 were subsequently examined. STING was elevated in the kidney tissue of LN patients and MRL/lpr mice. Compared with the MRL/lpr group, liproxstatin-1 or ferrostatin-1 treatment alleviated ferroptosis-related indicators 4-HNE, MDA, ROS, iron ion release, and GPX4 and SLC7A1 expression, whereas the treatment enhanced ACSL4 expression. STING interference observably decreased 4-HNE, ROS, MDA, iron ion, STING, and ACSL4 levels, and increased GPX4 and SLC7A11 expression in MRL/lpr mice kidney tissues. Besides, inhibition of STING reduced kidney tissue damage and inflammatory cell infiltration in MRL/lpr mice, and levels of serum creatinine, blood urea nitrogen, serum anti-double-stranded DNA antibody, inflammatory factors IL-6, IL-1ß, and TNF-α, as well as phosphorylation of NF-κB were all significantly decreased in MRL/lpr mice. TBK1 over expression reversed the impact of STING inhibition on ferroptosis and inflammatory response. STING contributed to ferroptosis and inflammatory response by activating the TBK1/NF-κB pathway, suggesting that STING may be a potent therapeutic target in LN.
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Ferroptosis , Nefritis Lúpica , Animales , Humanos , Ratones , Creatinina , Ferroptosis/genética , Interleucina-6 , Hierro , Nefritis Lúpica/genética , Ratones Endogámicos MRL lpr , FN-kappa B/genética , Proteínas Serina-Treonina Quinasas/genética , Especies Reactivas de Oxígeno , Transducción de Señal/genética , Factor de Necrosis Tumoral alfa , Regulación hacia ArribaRESUMEN
BACKGROUND: Previous studies have suggested anthocyanidins or anthocyanidin-rich foods and extracts exhibit protective effects against various cancers. However, the relationship between dietary anthocyanidins and the risk of biliary cancer remains uncertain. METHODS: This study used data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial to investigate the relationship between total anthocyanidins intake and biliary cancer incidence. Cox regression analysis was conducted to estimate HRs and corresponding 95% confidence intervals (CI) for the incidence of biliary cancer, with adjustments made for confounding factors. A restricted cubic spline model was employed to examine the dose-response relationship. In addition, subgroup and sensitivity analyses were conducted to evaluate potential interactions and test the model's robustness. RESULTS: During 8.9 years and 872,645.3 person-years of follow-up, 95 cases of biliary cancer were observed. The incidence rate of biliary cancer in this study was 11 cases per 100,000 person-years. Using the fully adjusted Cox regression model, the inverse association was observed between total anthocyanidins intake and the risk of biliary cancer (HR Q4 vs..Q1: 0.52; 95% CI: 0.29-0.91; Ptrend = 0.043). This association remained significant in sensitivity analyses. A linear dose-response relationship (Pnonlinearity = 0.118) and potential interaction with drinking status (Pinteraction = 0.033) were identified. CONCLUSIONS: This study provides evidence of an inverse association between total anthocyanidins intake and biliary cancer incidence. IMPACT: Our study found a total anthocyanidin-rich diet was associated with a reduced risk of biliary cancer in Americans ages 55 to 74 years.
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Neoplasias del Sistema Biliar , Neoplasias Ováricas , Masculino , Femenino , Humanos , Estados Unidos/epidemiología , Estudios Prospectivos , Antocianinas , Dieta , Riesgo , Neoplasias Ováricas/epidemiología , Neoplasias del Sistema Biliar/epidemiología , Factores de RiesgoRESUMEN
Aggravated endoplasmic reticulum stress (ERS) and apoptosis in podocytes play an important role in lupus nephritis (LN) progression, but its mechanism is still unclear. Herein, the role of SMURF1 in regulating podocytes apoptosis and ERS during LN progression were investigated. MRL/lpr mice was used as LN model in vivo. HE staining was performed to analyze histopathological changes. Mouse podocytes (MPC5 cells) were treated with serum IgG from LN patients (LN-IgG) to construct LN model in vitro. CCK8 assay was adopted to determine the viability. Cell apoptosis was measured using flow cytometry and TUNEL staining. The interactions between SMURF1, YY1 and cGAS were analyzed using ChIP and/or dual-luciferase reporter gene and/or Co-IP assays. YY1 ubiquitination was analyzed by ubiquitination analysis. Our results found that SMURF1, cGAS and STING mRNA levels were markedly increased in serum samples of LN patients, while YY1 was downregulated. YY1 upregulation reduced LN-IgG-induced ERS and apoptosis in podocytes. Moreover, SMURF1 upregulation reduced YY1 protein stability and expression by ubiquitinating YY1 in podocytes. Rescue studies revealed that YY1 knockdown abrogated the inhibition of SMURF1 downregulation on LN-IgG-induced ERS and apoptosis in podocytes. It was also turned out that YY1 alleviated podocytes injury in LN by transcriptional inhibition cGAS/STING/IFN-1 signal axis. Finally, SMURF1 knockdown inhibited LN progression in vivo. In short, SMURF1 upregulation activated the cGAS/STING/IFN-1 signal axis by regulating YY1 ubiquitination to facilitate apoptosis in podocytes during LN progression.
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Nefritis Lúpica , Humanos , Animales , Ratones , Nefritis Lúpica/patología , Ratones Endogámicos MRL lpr , Ubiquitinación , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/metabolismo , Inmunoglobulina G/metabolismo , Factor de Transcripción YY1/genética , Factor de Transcripción YY1/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
BACKGROUND: There is little prospective evidence exists about whether adherence to a diabetes risk reduction diet (DRRD) is related to a significant reduction in renal cancer risk. We sought to clarify whether adherence to DRRD was associated with a reduced risk of renal cancer in a US population. METHODS: A population-based cohort of 101,755 American adults was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. A DRRD score was calculated to assess adherence to this dietary pattern, where increased scores indicated greater adherence. The relationship between DRRD score and risk of renal cancer was assessed based on the hazard ratios (HRs) and 95% confidence intervals (CIs), which were both calculated using Cox regression. Non-linear association was determined through restricted cubic spline regression. Potential effect modifiers were identified through subgroup analyses. RESULTS: Over a mean follow-up of 8.8 years, 446 renal cancers were detected. In this analysis, the fully adjusted model depicted a notable 29% reduction in the risk of renal cancer among individuals in the highest quartile of DRRD score in comparison with the lowest quartile individuals (HRQ4 vs. Q1: 0.71; 95% CI = 0.54, 0.94; Ptrend = 0.008). This association remained consistent across a series of sensitivity analyses. A non-linear inverse dose-response association between renal cancer risk with DRRD score was observed (Pnonlinearity = 0.026). Subgroup analyses showed that this favorable link was more prominent in participants with low Healthy Eating Index-2015 (Pinteraction = 0.015). Regarding the individual components of DRRD, a decrease in the risk of renal cancer was linked to increased intake of cereal fiber and whole fruit, and lower sugar-sweetened beverage consumption (all Ptrend < 0.05). CONCLUSIONS: Our findings indicate that individuals adhering to DRRD are associated with a reduction in the risk of renal cancer.
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Diabetes Mellitus , Neoplasias Renales , Masculino , Adulto , Humanos , Estados Unidos/epidemiología , Estudios Prospectivos , Dieta , Dieta Reductora , Neoplasias Renales/epidemiología , Conducta de Reducción del Riesgo , Factores de RiesgoRESUMEN
Background: Adherence to the diabetes risk reduction diet (DRRD) may potentially reduce the risk of developing head and neck cancer (HNC) as the diet includes fruits and limits red and processed meats, known risk factors for HNC. However, there is currently no epidemiological research to investigate this potential association. Methods: The present study utilized data on demographics, lifestyles, medications, and diets of participants from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to explore the potential association between adherence to DRRD and the risk of HNC. We used a DRRD score to evaluate adherence to the dietary pattern and employed Cox regression analysis to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for HNC risk. Several subgroup analyses were carried out to identify potential effect modifiers, and multiple sensitivity analyses were performed to evaluate the stability of the correlation. The nine components of the DRRD was assessed separately for its association with the risk of HNC. Results: During a mean follow up of 8.84 years, 279 cases of HNC were observed. DDRD score was found to be inversely associated with the risk of HNC (HR Q4 vs. Q1: 0.582; 95% CI: 0.396, 0.856; p = 0.005 for trend) in a linear dose-response manner (p = 0.211 for non-linearity). Subgroup analysis indicated this inverse correlation was more pronounced among participants who had never smoked (HRQ4 vs. Q1: 0.193; 95% CI: 0.073, 0.511; p < 0.001 for trend) compared to current or former smokers (p = 0.044 for interaction). The primary association of DDRD and HNC risk remained robust after several sensitivity analyses. Regarding the individual components of DRRD, an inverse association was also observed between the risk of HNC and increased intake of cereal fiber and whole fruit (all p < 0.05 for trend). Conclusion: Our findings provide evidence that following the DRRD pattern may reduce the risk of NHC, especially for non-smokers.
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Previous research has shown that adhering to the Eat-Lancet diet (ELD) is associated with a lower risk of chronic diseases and mortality. However, the associations between ELD and lung cancer incidence and mortality are unclear. To address this gap, we conducted a prospective cohort study involving 101,755 adults from the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial in the USA. The ELD score was utilized to assess compliance with the ELD, with higher scores indicating greater compliance. We employed Cox regression analyses to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of ELD score with the incidence and mortality of lung cancer and its subtypes. In addition, sensitivity analyses were performed to ensure the robustness of our findings. In total, 1706 cases of lung cancer and 1217 lung cancer-associated deaths were recorded during the study period. Our analysis revealed that higher ELD scores were significantly associated with a reduced incidence (HRQuartile 4 vs. Quartile 1 : 0.73; 95% CI: 0.60, 0.89; ptrend = 0.001) and mortality (HRQuartile 4 vs. Quartile 1 : 0.74; 95% CI: 0.59, 0.93; ptrend = 0.005) of lung cancer in a dose-response manner (all pnonlinearity > 0.05). The reliability of these results was supported by sensitivity analyses. Notably, these associations were primarily observed in non-small-cell lung cancer. In conclusion, our findings suggest that adherence to the ELD may be associated with a reduced risk of lung cancer incidence and mortality.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Masculino , Adulto , Humanos , Neoplasias Pulmonares/epidemiología , Estudios Prospectivos , Factores de Riesgo , Incidencia , Reproducibilidad de los Resultados , DietaRESUMEN
Background: Sulfur microbial diet (SMD), related to the enrichment of sulfur-metabolizing gut bacteria, has been confirmed to be linked to an elevated risk of early-onset colorectal adenoma in young females. However, it remains unclear whether SMD is associated with the risk of colorectal adenoma in older people, who are at greater risk for colorectal cancer. Methods: All data on participants in this study were retrieved from the intervention arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening test. Participants' adherence to this dietary pattern was assessed using SMD score. Hazard ratios (HR) and 95% confidence intervals (CI) were adopted in Cox proportional hazards regression models to assess the link between SMD score and the incidence of colorectal adenoma in participants included in the study. Specific stratified analyses were constructed to assess whether this association changed in different conditions, whereas the robustness of the association was examined through sensitivity analyses. Results: The mean baseline age of participants was 62.1 (SD 5.2) years (range 54.0-75.0 years). During 19,468,589 person-years of follow-up, 992 colorectal adenoma cases were documented in a total of 17,627 included participants. In a fully adjusted model, an increased risk of colorectal adenoma was determined in participants in the highest quartile of SMD score in comparison with those in the lowest quartile (HRquartile4 vs. HRquartile1 = 1.23; 95% CI: 1.02, 1.47; p = 0.017 for trend). This positive association between SMD score and adenoma risk was more evident in participants who were current or former smokers (p = 0.029 for interaction). Conclusion: In this study, our results support a role for the SMD in the carcinogenicity of colorectal cancer precursors among older adults. Nevertheless, these results require validation through more research.
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BACKGROUND: The plant-based paleolithic diet (PD) and the paleolithic-like lifestyle (PLL) may reduce the risk of chronic diseases, including colorectal adenomas. These dietary and lifestyle approaches are proposed to exert their effects through mechanisms such as reducing inflammation, oxidative stress, and insulin levels. However, whether PD and PLL is associated with the risk of colorectal cancer (CRC) has not been determined. METHODS: A cohort of 74,721 individuals who participated in the PLCO study were included in this analysis. Adherence to the PD and PLL was assessed using PD and PLL scores, where higher scores indicated greater adherence. Multivariable Cox models were utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of CRC and its subsites (proximal colon cancer and distal CRC). Subgroup analyses were conducted to identify potential effect modifiers. RESULTS: During a mean follow-up of 9.2 years, a total of 694 CRC cases were identified. Participants in the highest compared with the lowest quartiles of PD score had a lower risk of CRC (Q4 vs Q1: HR 0.76, 95% CI 0.61-0.95, Ptrend = 0.009) and proximal colon cancer (Q4 vs Q1: HR 0.73, 95% CI 0.55-0.97, Ptrend = 0.02). A stronger inverse association was observed for PLL score with the risk of CRC (Q4 vs Q1: HR 0.64, 95% CI 0.51-0.81, Ptrend < 0.001), proximal colon (Q4 vs Q1: HR 0.62, 95% CI 0.46-0.83, Ptrend = 0.001) and distal CRC (Q4 vs Q1: HR 0.69, 95% CI 0.48-0.98, Ptrend = 0.03). Subgroup analyses revealed the inverse association of PD score with the risk of CRC was more pronounced in participants with BMI < 30 (Q4 vs Q1: HR 0.68, 95% CI 0.53-0.87) than in those with BMI ≥ 30 (Q4 vs Q1: HR 1.07, 95% CI 0.68-1.67) (Pinteraction = 0.02). CONCLUSIONS: Our findings suggest that adhering to the PD and PLL could be a new option to reduce CRC risk.
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Neoplasias del Colon , Neoplasias Colorrectales , Humanos , Estados Unidos , Factores de Riesgo , Dieta Paleolítica , Estudios Prospectivos , Dieta , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/prevención & control , Estilo de VidaRESUMEN
BACKGROUND: Venous thromboembolism (VTE) is a serious and preventable postoperative complication. However, the predictive significance of perioperative biochemical parameters for VTE after minimally invasive colorectal cancer surgery remains unclear. METHODS: A total of 149 patients undergoing minimally invasive colorectal cancer surgery were collected between October 2021 and October 2022. Biochemical parameters related to preoperative and postoperative day 1, day 3, and day 5 were collected, including D-Dimer, mean platelet volume (MPV), and maximum amplitude (MA) of thromboelastography (TEG). Receiver operating characteristic (ROC) curves were used to explore the predictive powers of meaningful biochemical parameters for postoperative VTE, and calibration curves were used to assess predictive accuracy. RESULTS: The overall cumulative incidence of VTE was 8.1% (12/149). The preoperative and postoperative day 3 D-Dimer, postoperative day 3, and day 5 MPV, and postoperative day 1, day 3, and day 5 TEG-MA was significantly higher in the VTE group than in the non-VTE group (P < 0.05). The results of both the ROC curve and the calibration curve indicated that these meaningful D-Dimer, MPV, and TEG-MA had moderate discrimination and consistency for postoperative VTE. CONCLUSIONS: D-Dimer, MPV, and TEG-MA may predict postoperative VTE in patients undergoing minimally invasive surgery for colorectal cancer at specific times in the perioperative period.
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Neoplasias Colorrectales , Tromboembolia Venosa , Humanos , Neoplasias Colorrectales/cirugía , Tromboembolia Venosa/complicaciones , Tromboembolia Venosa/epidemiología , Complicaciones Posoperatorias , Procedimientos Quirúrgicos Mínimamente Invasivos , Tromboelastografía , Estudios Retrospectivos , Masculino , Femenino , Adulto , Persona de Mediana Edad , AncianoRESUMEN
Liver hepatocellular carcinoma (LIHC) is one of the main cancers worldwide and has high morbidity and mortality rates. Although previous studies have shown that ANXA10 is expressed at low levels in LIHC tumor tissues, the biological function of ANXA10 in LIHC is still unclear. Therefore, we utilized TCGA, TIMER, GEPIA2, TISIDB, LinkedOmics, ssGSEA algorithms and CIBERSORT methodology to preliminarily evaluate the potential mechanism of ANXA10 in LIHC. In vitro experiments were used to further verify some functions of ANXA10. Consequently, we found that ANXA10 mRNA/protein expression was downregulated in LIHC tissue compared to normal tissue. ANXA10 was significantly linked with clinicopathological features, immunocytes, multiple cancer-related pathways, m6A modification and a ceRNA network. A three-gene prognostic signature rooted in ANXA10-related immunomodulators was determined and found to be an independent prognostic predictor. A nomogram was constructed to predict survival with good accuracy. Additionally, in vitro trials revealed that ANXA10 upregulation inhibited LIHC cell proliferation and migration. This study reveals that ANXA10 may serve as a prognostic marker and promising therapeutic target in LIHC clinical practice through various biologic functions.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Pronóstico , Neoplasias Hepáticas/genética , Biología Computacional , Biomarcadores , Anexinas/genéticaRESUMEN
Background: The intricate role of oxidative stress (OS) in colorectal cancer (CRC) initiation is underscored by an imbalance between pro-oxidants and antioxidants. Utilizing the Oxidative Balance Score (OBS) as a metric, this study aims to investigate the association between OS exposure and CRC risk, while also examining potential sex-specific differences in a large U.S. cohort. Methods: The study included 98,395 adults from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. To construct the OBS, 14 dietary and lifestyle factors intricately associated with oxidative stress were quantified. A higher OBS value indicated a more favorable oxidative balance pattern or diminished OS exposure. Due to sex-specific differences in OBS, associations were evaluated separately for men and women based on Cox regression analysis. Subgroup analyses were conducted to elucidate potential modifiers. Results: During 867,963.4 person-years of follow-up, 1,054 CRCs occurred. The mean (SD) age and OBS were 65.52 (5.73) years and 14.09 (3.95) points, respectively. In the fully adjusted Cox model, we observed an inverse association between OBS and CRC incidence in women (HRQ5vsQ1: 0.72; 95% CI: 0.52, 0.99; P for trend = 0.018) but not men. Subgroup analyses revealed the inverse association was more pronounced among women without versus with a family history of CRC (HRQ5 vsQ1: 0.66, 95% CI: 0.47-0.93; P for trend = 0.001; P for interaction = 0.001). The results remained robust after several sensitivity analyses. Conclusion: Higher OBS was associated with lower CRC risk in women but not men; this inverse association was stronger among women without a family history of CRC. These findings suggest exposure to OS may confer sex-specific CRC risk effects, especially for women without a family history of CRC.
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Background: Low-fat diet reduces the risk of chronic metabolic diseases such as obesity and diabetes, which exhibit overlapping mechanisms with liver cancer. However, the association between low-fat diet and liver cancer risk remains unclear. Aim: To investigate whether adherence to low-fat diet is associated with a reduced risk of liver cancer in a prospective study. Materials and methods: Data of participants in this study were collected from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. A low-fat diet score was calculated to reflect adherence to low-fat dietary pattern, with higher scores indicating greater adherence. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for liver cancer incidence with adjustment for potential covariates. Restricted cubic spline model was used to characterize liver cancer risk across the full range of the low-fat diet score. Prespecified subgroup analyses were used to identify potential impact modifiers. Sensitivity analyses were performed to test the robustness of this association. Results: A total of 98,455 participants were included in the present analysis. The mean (standard deviation) age, low-fat diet score, and follow-up time were 65.52 (5.73) years, 14.99 (6.27) points, and 8.86 (1.90) years, respectively. During 872639.5 person-years of follow-up, 91 liver cancers occurred, with an overall incidence rate of 0.01 cases per 100 person-years. In the fully adjusted Cox model, the highest versus the lowest quartile of low-fat diet score was found to be associated with a reduced risk of liver cancer (HR Q4 vs. Q1: 0.458; 95% CI: 0.218, 0.964; P = 0.035 for trend), which remained associated through a series of sensitivity analyses. The restricted cubic spline model showed a linear dose-response association between low-fat diet score and liver cancer incidence (p = 0.482 for non-linear). Subgroup analyses did not show significant interaction between low-fat diet score and potential impact modifiers in the incidence of liver cancer. Conclusion: In this study, low-fat diet score is associated with reduced liver cancer risk in the US population, indicating that adherence to low-fat diet may be helpful for liver cancer prevention. Future studies should validate our findings in other populations.
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Background: Solid pseudopapillary neoplasm (SPN) is a rare tumor with low malignant potential, which typically occurs in the pancreas. Extrapancreatic SPN is also extremely rare worldwide. Case presentation: We report a case of a 70-year-old woman hospitalized with abdominal pain and bloating. The patient did not have any underlying diseases, such as diabetes, coronary heart disease, or hypertension. More than 30 years ago, the patient underwent surgery for "ectopic pregnancy". The patient had no family history of hereditary disease, nor did any immediate family members have a history of cancer. Laboratory tests showed that her hemoglobin and albumin levels were low and she had a high level of cancer antigen 125 (CA125). Enhanced computed tomography (CT) showed a large tumor in the abdomen and pelvis. The patient subsequently underwent surgery, and it was found that the tumor was attached to the terminal ileum. Pathological findings suggested that the tumor was an extrapancreatic SPN, with an ectopic pancreas found in the tumor tissue. The patient did not receive chemotherapy or radiotherapy after surgery. After 13 months of follow-up, the patient was admitted again with abdominal pain. CT showed tumor recurrence with extensive systemic metastases. The patient and her family refused reoperation and biopsy, and the patient was discharged after the abdominal pain and anemia resolved. Conclusion: We report a rare case of extrapancreatic SPN of ileal origin, which could be the first report worldwide. It had aggressive biological features, with recurrence and metastasis 13 months after surgery. For extrapancreatic SPN, the risk of recurrence should be assessed, and for tumors suspected of malignant behavior, a longer follow-up after discharge may be needed. Although SPN generally has a good prognosis after surgery, there is no consensus on whether postoperative chemotherapy and other treatments are needed for patients with high recurrence risk.
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Background: There is great mental stress due to the coronavirus disease 2019 (COVID-19) pandemic. However, there are no detailed psychological studies of the children with chronic kidney disease (CKD) and their guardians during the COVID-19 pandemic. Objective: This study explores the psychological pressure on children with CKD and their guardians. Methods: An online survey was conducted at 20 of the largest pediatric nephropathy departments in China, including the Rutter Parent Questionnaire, Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). Overall, 885 children (589 children with CKD associated with 296 children of the control group) completed the survey together with their guardians. Results: There was no statistical difference between CKD children and control children regarding their Rutter behavior scores and abnormal behaviors. Nevertheless, the abnormal behavior of children might aggravate the anxiety and depression of guardians in both CKD and control groups (p < 0.05). We confirmed that the anxiety and depression of guardians in the CKD group were both significantly higher than those in the control group (p < 0.05). The guardians in the CKD group with lower annual income were more likely to experience anxiety (p < 0.05). Furthermore, the guardians whose children were older than 11 years old might be more anxious than those who were 6-11 years old. Besides, the guardians in the CKD group who watched the news for 30-60 min daily were less likely to have depression than those who watched < 10 min (p < 0.05). The subgroup results showed that the gender, the time of watching the news, the annual income of guardians, and children's age might be the most critical factors influencing guardians' psychological burden. Conclusion: The guardians in the CKD group have more severe anxiety and depression during the pandemic. The children's abnormal behavior, adolescents' pressure, low household income, and the panic about the pandemic may be the main reasons for the anxiety and depression of guardians.
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COVID-19 , Insuficiencia Renal Crónica , Niño , Adolescente , Humanos , Pandemias , COVID-19/epidemiología , Ansiedad/epidemiología , Ansiedad/psicología , Estrés Psicológico , Insuficiencia Renal Crónica/epidemiologíaRESUMEN
A kinase anchor protein 12 (AKAP12) as a tumor suppressor in various cancers has been extensively studied and confirmed. However, its immune implication in stomach adenocarcinoma (STAD) remains uncertain. Here, using The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), Tumor Immune Estimation Resource (TIMER), Cancer Cell Line Encyclopedia (CCLE), integrated repository portal for tumor-immune system interactions (TISIDB), and Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) database, we systematically analyzed the immune correlation of AKAP12 from three aspects including immune infiltration cells, immune-related pathways, and immunomodulators and developed a AKAP12-related 4-gene signature for prognosis prediction. Our results showed that AKAP12 mRNA and protein levels were downregulated in STAD patients, and its expression was positively related to CD4+ T cells and macrophages. In addition, the immune cell infiltration levels were associated with AKAP12 gene copy number deletion in STAD. Based on CCLE database, we found that AKAP12 coexpressed genes were enriched in several immune- and cancer-related pathways, which was further validated by Gene Set Enrichment Analysis (GSEA). Moreover, we identified 46 immunomodulators that were significantly related to AKAP12 expression using TISIDB database, and these immunomodulators were involved in immune-related pathways including Th17 cell differentiation and natural killer cell-mediated cytotoxicity. Additionally, based on the 46 AKAP12-related immunomodulators, a 4-gene risk prediction signature was developed using the Cox regression model. The risk signature was identified as an independent prognostic factor, which can accurately predict the prognosis of patients with STAD, showing good predictive performance. Furthermore, we constructed a prognostic nomogram and calibration to predict and assess patient survival probabilities by integrating the risk score and other clinical factors. In conclusion, our study provides strong evidence that AKAP12 is closely related to tumor immunity in STAD from three aspects: immune infiltration cells, immune pathways, and immunomodulators. More importantly, the AKAP12-related prognostic signature may have a good application prospect for clinical practice.
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Adenocarcinoma , Neoplasias Gástricas , Proteínas de Anclaje a la Quinasa A/genética , Adenocarcinoma/genética , Adenocarcinoma/patología , Proteínas de Ciclo Celular , Humanos , ARN Mensajero , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologíaRESUMEN
OBJECTIVE: To observe the efficacy and safety of telitacicept in refractory childhood-onset systemic lupus erythematosus (cSLE). METHODS: A self-controlled before-after trial. Children with active SLE, aged 5-18 years, who cannot tolerate side effects of glucocorticoid, were enrolled in our study. Patients received subcutaneous injection of telitacicept weekly based on the standard treatment. SLE responder index-4 (SRI-4) was assessed before the first administration and at least 4 weeks after the first administration. RESULTS: Among the 15 cases of refractory cSLE, three were males (20%) and 12 were females (80%). The median age and weight were 13 years old and 52 kg, respectively. The median duration of disease was 30 months. 5-26 weeks (80 or 160 mg per week) after administration of telitacicept, 66.7% (n=10) reached SRI-4 response. 12 cases reduced their glucocorticoid intake from 40 mg/d to 17.5 mg/d. The urinary protein after treatment declined in 8 cases whose 24-h proteinuria was >0.5 g at baseline. The urinary protein in two of the eight cases turned negative and plasma albumin in five of the eight cases rose to normal. In addition, three of these eight cases demonstrated varying degrees of improvement in renal impairment, whose estimated glomerular filtration rate (eGFR, ml/min·1.73 m2) rose from 17.4 to 26.6, 40.7 to 48.2, and 63.2 to 146.0, respectively. There were mild to moderate adverse events after treatment. CONCLUSION: Telitacicept combined with the standard treatment may significantly increase the SRI-4 response rate and reduce the glucocorticoid dosage in refractory cSLE, and also shown efficacy on lupus nephritis. The related adverse drug events were controllable.
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Inmunosupresores , Lupus Eritematoso Sistémico , Adolescente , Niño , Preescolar , Femenino , Glucocorticoides/efectos adversos , Humanos , Inmunosupresores/efectos adversos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Masculino , Resultado del TratamientoRESUMEN
BACKGROUND: Currently, immunotherapy is widely used for breast cancer (BC) patients, and tumor mutation burden (TMB) is regarded as a valuable independent predictor of response to immunotherapy. However, specific gene mutations and their relationship with TMB and tumor-infiltrating immune cells in BC are not fully understood. METHODS: Comprehensive bioinformatic analyses were performed using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. Survival curves were analyzed via Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were used for prognosis analysis. Gene set enrichment analysis (GSEA) was performed to explore regulatory mechanisms and functions. The CIBERSORT algorithm was used to calculate the tumor-infiltrating immune cell fractions. RESULTS: We analyzed somatic mutation data of BC from TCGA and ICGC datasets and found that 19 frequently mutated genes were reported in both cohorts, namely, SPTA1, TTN, MUC17, MAP3K1, CDH1, FAT3, SYNE1, FLG, HMCN1, RYR2 (ryanodine receptor 2), GATA3, MUC4, PIK3CA, KMT2C, TP53, PTEN, ZFHX4, MUC16, and USH2A. Among them, we observed that RYR2 mutation was significantly associated with higher TMB and better clinical prognosis. Moreover, GSEA revealed that RYR2 mutation-enriched signaling pathways were related to immune-associated pathways. Furthermore, based on the CIBERSORT algorithm, we found that RYR2 mutation enhanced the antitumor immune response by enriching CD8+ T cells, activated memory CD4+ T cells, and M1 macrophages. CONCLUSION: RYR2 is frequently mutated in BC, and its mutation is related to increased TMB and promotes antitumor immunity; thus, RYR2 may serve as a valuable biomarker to predict the immune response.
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Neoplasias de la Mama/genética , Mutación/genética , Canal Liberador de Calcio Receptor de Rianodina/genética , Anciano , Biomarcadores de Tumor/genética , Biología Computacional/métodos , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Inmunoterapia/métodos , Estimación de Kaplan-Meier , Masculino , Pronóstico , Transducción de Señal/genéticaRESUMEN
OBJECTIVE: Colon cancer (CC) is one of the most common cancers whose progression is regulated by a number of factors, including circular RNAs (circRNAs). Nonetheless, circ_0038718 is a novel circRNA, and its regulatory mechanism in CC remains unclear. METHODS: Real-time quantitative PCR (qRT-PCR) was performed to detect the expression of circ_0038718, miR-195-5p and Axin2. Western blot was conducted to determine the protein expression of Axin2 and the key proteins on Wnt/ß-catenin signaling pathway. Oligo (dT) 18 primers and RNase R were employed to identify the circular features of circ_0038718, and the location of circ_0038718 in cells was detected via nucleocytoplasmic separation. Dual-luciferase reporter assay and RNA binding protein immunoprecipitation experiment were carried out to investigate the molecular mechanism of circ_0038718/miR-195-5p/Axin2. Additionally, MTT assay was conducted to assess cell proliferation; Transwell assay was performed to evaluate cell migration and invasion, respectively. The effect of circ_0038718 on CC tumor growth was tested through tumor formation in nude mice. RESULTS: circ_0038718 was highly expressed in CC and could sponge miR-195-5p in cytoplasm. Silencing circ_0038718 suppressed the proliferative, migratory and invasive abilities of CC cells, while the promoting effect of high circ_0038718 expression on CC cells was reversed upon miR-195-5p over-expression. Axin2 was a downstream target of miR-195-5p and could regulate the Wnt/ß-catenin signaling pathway. Axin2 expression was modulated by circ_0038718/miR-195-5p. Knockdown of Axin2 could also attenuate the promoting effect of high circ_0038718 expression on CC cell malignant progression, thus inhibiting tumor growth. CONCLUSION: circ_0038718 is able to facilitate CC cell malignant progression via the miR-195-5p/Axin2 axis, which will provide a new idea for finding a novel targeted treatment of CC.
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Neoplasias del Colon , MicroARNs , ARN Circular/genética , Vía de Señalización Wnt , Animales , Proteína Axina/genética , Línea Celular Tumoral , Neoplasias del Colon/genética , Ratones , Ratones Desnudos , MicroARNs/genética , Vía de Señalización Wnt/genética , beta CateninaRESUMEN
Systemic lupus erythematosus (SLE) is an autoimmune-mediated diffuse connective tissue disease characterized by immune inflammation with an unclear aetiology and pathogenesis. This work profiled the intestinal flora and faecal metabolome of patients with SLE using 16S RNA sequencing and gas chromatography-mass spectrometry (GC-MS). We identified unchanged alpha diversity and partially altered beta diversity of the intestinal flora. Another important finding was the increase in Proteobacteria and Enterobacteriales and the decrease in Ruminococcaceae among SLE patients. For metabolites, amino acids and short-chain fatty acids were enriched when long-chain fatty acids were downregulated in SLE faecal samples. KEGG analysis showed the significance of the protein digestion and absorption pathway, and association analysis revealed the key role of 3-phenylpropanoic acid and Sphingomonas. Sphingomonas were reported to be less abundant in healthy periodontal sites of SLE patients than in those of HCs, indicating transmission of oral species to the gut. This study contributes to the understanding of the pathogenesis of SLE disease from the perspective of intestinal microorganisms, explains the pathogenesis of SLE, and serves as a basis for exploring potential treatments for the disease.