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BACKGROUND: Integrins mediate the adhesion, crawling, and migration of neutrophils during vascular inflammation. Thiol exchange is important in the regulation of integrin functions. ERp72 (endoplasmic reticulum-resident protein 72) is a member of the thiol isomerase family responsible for the catalysis of disulfide rearrangement. However, the role of ERp72 in the regulation of Mac-1 (integrin αMß2) on neutrophils remains elusive. METHODS: Intravital microscopy of the cremaster microcirculation was performed to determine in vivo neutrophil movement. Static adhesion, flow chamber, and flow cytometry were used to evaluate in vitro integrin functions. Confocal fluorescent microscopy and coimmunoprecipitation were utilized to characterize the interactions between ERp72 and Mac-1 on neutrophil surface. Cell-impermeable probes and mass spectrometry were used to label reactive thiols and identify target disulfide bonds during redox exchange. Biomembrane force probe was performed to quantitatively measure the binding affinity of Mac-1. A murine model of acute lung injury induced by lipopolysaccharide was utilized to evaluate neutrophil-associated vasculopathy. RESULTS: ERp72-deficient neutrophils exhibited increased rolling but decreased adhesion/crawling on inflamed venules in vivo and defective static adhesion in vitro. The defect was due to defective activation of integrin Mac-1 but not LFA-1 (lymphocyte function-associated antigen-1) using blocking or epitope-specific antibodies. ERp72 interacted with Mac-1 in lipid rafts on neutrophil surface leading to the reduction of the C654-C711 disulfide bond in the αM subunit that is critical for Mac-1 activation. Recombinant ERp72, via its catalytic motifs, increased the binding affinity of Mac-1 with ICAM-1 (intercellular adhesion molecule-1) and rescued the defective adhesion of ERp72-deficient neutrophils both in vitro and in vivo. Deletion of ERp72 in the bone marrow inhibited neutrophil infiltration, ameliorated tissue damage, and increased survival during murine acute lung injury. CONCLUSIONS: Extracellular ERp72 regulates integrin Mac-1 activity by catalyzing disulfide rearrangement on the αM subunit and may be a novel target for the treatment of neutrophil-associated vasculopathy.
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Lesão Pulmonar Aguda , Antígeno de Macrófago 1 , Animais , Camundongos , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismo , Adesão Celular , Dissulfetos , Molécula 1 de Adesão Intercelular/metabolismo , Antígeno-1 Associado à Função Linfocitária/metabolismo , Antígeno de Macrófago 1/genética , Antígeno de Macrófago 1/metabolismo , Infiltração de Neutrófilos , Neutrófilos/metabolismo , Compostos de Sulfidrila/metabolismoRESUMO
Our study aimed to investigate the association between the transition of the TXNIP gene methylation level and the risk of incident type 2 diabetes mellitus (T2DM). This study included 263 incident cases of T2DM and 263 matched non-T2DM participants. According to the methylation levels of five loci (CpG1-5; chr1:145441102-145442001) on the TXNIP gene, the participants were classified into four transition groups: maintained low, low to high, high to low, and maintained high methylation levels. Compared with individuals whose methylation level of CpG2-5 at the TXNIP gene was maintained low, individuals with maintained high methylation levels showed a 61-87% reduction in T2DM risk (66% for CpG2 [OR: 0.34, 95% CI: 0.14, 0.80]; 77% for CpG3 [OR: 0.23, 95% CI: 0.07, 0.78]; 87% for CpG4 [OR: 0.13, 95% CI: 0.03, 0.56]; and 61% for CpG5 [OR: 0.39, 95% CI: 0.16, 0.92]). Maintained high methylation levels of four loci of the TXNIP gene are associated with a reduction of T2DM incident risk in the current study. Our study suggests that preserving hypermethylation levels of the TXNIP gene may hold promise as a potential preventive measure against the onset of T2DM.
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Proteínas de Transporte , Ilhas de CpG , Metilação de DNA , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/epidemiologia , Metilação de DNA/genética , Masculino , Proteínas de Transporte/genética , Feminino , Estudos de Casos e Controles , Pessoa de Meia-Idade , Idoso , Predisposição Genética para Doença , Fatores de Risco , AdultoRESUMO
BACKGROUND: The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and triglyceride-glucose (TyG) index are novel indexes for insulin resistance (IR). We aimed to evaluate associations of TG/HDL-C and TyG with arterial stiffness risk. METHODS: We enrolled 1979 participants from the Rural Chinese Cohort Study, examining arterial stiffness by brachial-ankle pulse wave velocity (baPWV). Logistic and linear regression models were employed to calculate effect estimates. For meta-analysis, we searched relevant articles from PubMed, Embase and Web of Science up to August 26, 2023. The fixed-effects or random-effects models were used to calculate the pooled estimates. We evaluated dose-response associations using restricted cubic splines. RESULTS: For cross-sectional studies, the adjusted ORs (95%CIs) for arterial stiffness were 1.12 (1.01-1.23) and 1.78 (1.38-2.30) for per 1 unit increment in TG/HDL-C and TyG. In the meta-analysis, the pooled ORs (95% CIs) were 1.26 (1.14-1.39) and 1.57 (1.36-1.82) for per 1 unit increment of TG/HDL-C and TyG. Additionally, both TG/HDL-C and TyG were positively related to PWV, with ß of 0.09 (95% CI 0.04-0.14) and 0.57 (95% CI 0.35-0.78) m/s. We also found linear associations of TG/HDL-C and TyG with arterial stiffness risk. CONCLUSIONS: High TG/HDL-C and TyG were related to increased arterial stiffness risk, indicating TG/HDL-C and TyG may be convincing predictors of arterial stiffness.
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Resistência à Insulina , Rigidez Vascular , Humanos , Glucose , Triglicerídeos , Estudos de Coortes , Índice Tornozelo-Braço , Rigidez Vascular/fisiologia , HDL-Colesterol , Estudos Transversais , Análise de Onda de Pulso , Resistência à Insulina/genética , Glicemia , BiomarcadoresRESUMO
PURPOSE: This meta-analysis evaluated the relationship between overweight/obesity and depressive disorders in children and adolescents. METHODS: We examined the databases of PubMed, Embase and Web of Science for pertinent observational studies released up until 20 February 2022. The pooled relative risks (RRs) and 95% confidence intervals (CIs) of obesity and overweight with depressive disorder were calculated by means of random-effects models. The Newcastle-Ottawa Quality Assessment Scale and Agency for Healthcare Research and Quality scale were adopted to evaluate the study quality. RESULTS: Finally, for this meta-analysis, we evaluated 22 observational publications covering 175 135 participants (5 cohort study articles, 1 case-control study article and 16 cross-sectional study articles). A significant positive association was found between obesity and the risk of depression (RR 1.32, 95% CI 1.09-1.60, I2 = 79.90%, Pheterogeneity < 0.001) and in the association between obesity and depressive symptoms (RR 1.16, 95% CI: 1.00-1.35, I2 = 25.0%, Pheterogeneity = 0.247). On sensitivity analysis, the pooled RRs remained robust. Subgroup analysis indicated that obese children and teenagers in western countries were more prone to depression. CONCLUSION: Evidence from this meta-analysis, based on observational studies, supported the idea that obese children and adolescents are more likely to experience depression and depressive symptoms.
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Transtorno Depressivo , Obesidade Infantil , Adolescente , Humanos , Criança , Sobrepeso , Obesidade Infantil/complicações , Obesidade Infantil/epidemiologia , Estudos de Coortes , Estudos Transversais , Estudos de Casos e Controles , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/etiologia , Estudos Observacionais como AssuntoRESUMO
While noise pollution from transportation has become an important public health problem, the relationships between different sources of traffic noise and cardiovascular diseases (CVDs) remain inconclusive. A comprehensive meta-analysis was therefore conducted to quantitatively assess the effects of long-term exposure to road traffic, railway, and aircraft noise on CVDs and relevant subtypes. We systematically retrieved PubMed, Embase, and Web of Science for articles published before April 4, 2022. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated by the fixed- or random-effects models. In total, 23 articles were included in our meta-analysis. The risk of CVDs increased by 2% (RR 1.020, 95% CI 1.006-1.035) and 1.6% (RR 1.016, 95% CI 1.000-1.032) for every 10 dB increment of road traffic and aircraft noise. For CVD subtypes, the risk increased by 3.4% (1.034, 1.026-1.043) for stroke and 5% (1.050, 1.006-1.096) for heart failure with each 10 dB increment of road traffic noise; the risk of atrial fibrillation increased by 1.1% (1.011, 1.002-1.021) with each 10 dB increment of railway noise; and the risk increased by 1% (1.010, 1.003-1.017) for myocardial infarction, 2.7% (1.027, 1.004-1.050) for atrial fibrillation, and 2.3% (1.023, 1.016-1.030) for heart failure with each 10 dB increment in aircraft noise. Further, effects from road traffic, railway, and aircraft noise all followed positive linear trends with CVDs. Long-term exposure to traffic noise is positively related to the incidence risk of cardiovascular events, especially road traffic noise which significantly increases the risk of CVDs, stroke, and heart failure.
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Fibrilação Atrial , Doenças Cardiovasculares , Insuficiência Cardíaca , Ruído dos Transportes , Acidente Vascular Cerebral , Humanos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Ruído dos Transportes/efeitos adversos , Fibrilação Atrial/complicações , Insuficiência Cardíaca/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Exposição Ambiental/efeitos adversosRESUMO
Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, has resulted thus far in greater than 933,000 deaths worldwide; yet disease pathogenesis remains unclear. Clinical and immunological features of patients with COVID-19 have highlighted a potential role for changes in immune activity in regulating disease severity. However, little is known about the responses in human lung tissue, the primary site of infection. Here we show that pathways related to neutrophil activation and pulmonary fibrosis are among the major up-regulated transcriptional signatures in lung tissue obtained from patients who died of COVID-19 in Wuhan, China. Strikingly, the viral burden was low in all samples, which suggests that the patient deaths may be related to the host response rather than an active fulminant infection. Examination of the colonic transcriptome of these patients suggested that SARS-CoV-2 impacted host responses even at a site with no obvious pathogenesis. Further proteomics analysis validated our transcriptome findings and identified several key proteins, such as the SARS-CoV-2 entry-associated protease cathepsins B and L and the inflammatory response modulator S100A8/A9, that are highly expressed in fatal cases, revealing potential drug targets for COVID-19.
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COVID-19/metabolismo , Proteoma/metabolismo , Transcriptoma , Idoso , Idoso de 80 Anos ou mais , COVID-19/genética , COVID-19/imunologia , COVID-19/patologia , Colo/metabolismo , Evolução Fatal , Feminino , Humanos , Pulmão/metabolismo , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Ativação de Neutrófilo , Proteoma/genética , SARS-CoV-2/patogenicidade , Carga ViralRESUMO
BACKGROUND: Lung cancer is the leading cause of malignancy-related mortality and lung adenocarcinoma accounts for about 40% of lung malignancies. The aim of this study was to investigate the associations of intraflagellar transport protein 20 (IFT20) and Golgi matrix protein 130 (GM130) expression with clinicopathological features and survival in patients with lung adenocarcinoma. METHODS: The expressions of IFT20 and GM130 protein in cancerous and matched adjacent lung tissues of 235 patients with lung adenocarcinoma were assessed by tissue microarray and immunohistochemistry, which were indicated by the mean optical density (IOD/area), the rate of positive staining cells and staining intensity score. The correlation between IFT20 and GM130 protein was assessed by Spearman's rank correlation. Associations of IFT20 and GM130 protein expression with clinicopathological features of patients were analyzed by multivariate logistic regression models. The survival analysis of patients was performed by Cox proportional hazard regression models. RESULTS: With adjustment for multiple potential confounders, each one-point increase in IFT20 protein staining intensity score was significantly associated with 32% and 29% reduced risk for TNM stage in II ~ IV and lymphatic metastasis of patients, respectively (P < 0.05). And each one-point increase in GM130 protein staining intensity score was associated with a significant reduction in the risk of poor differentiation and tumors size > 7 cm by 29% and 38% for lung adenocarcinoma patients, respectively (P < 0.05). In stratified Cox model analysis, enhanced IFT20 staining intensity score was significantly decreased the risk of death by 16% for patients without distant metastasis. And elevated the IOD/area of GM130 expression significantly decreased the death risk of lung adenocarcinoma patients with tumor size > 7 cm or distant metastasis by 54% and 65%, respectively (P < 0.05). CONCLUSION: IFT20 and GM130 protein expressions were negatively associated with tumor differentiated types, size, TNM stage and lymphatic metastasis of lung adenocarcinoma. Both IFT20 and GM130 proteins have some protective effects on the survival of lung adenocarcinoma patients with specific clinicopathological features.
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Adenocarcinoma de Pulmão , Adenocarcinoma , Autoantígenos/metabolismo , Neoplasias Pulmonares , Proteínas de Membrana/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/metabolismo , Proteínas de Transporte , Humanos , Neoplasias Pulmonares/patologia , Metástase Linfática , Estadiamento de Neoplasias , PrognósticoRESUMO
BACKGROUND: The objective of this study was to develop and validate a nomogram to predict 1-year overall survival (OS) and 2-year OS in patients with high-grade digestive neuroendocrine neoplasms (NENs) as well as to guide selection of subgroups that could benefit from systemic chemotherapy. SUBJECTS, MATERIALS, AND METHODS: We performed a retrospective analysis of 223 patients with NENs of the gut and hepato-biliary-pancreatic system from four centers included in the development cohort. The nomogram was externally validated in a cohort of 90 patients from another one. RESULTS: The final model included lactate dehydrogenase, performance status, stage, Ki67, and site of primary tumor, all of which had a significant effect on OS. The uncorrected C-index was 0.761 for OS, and the bias-corrected C-index was 0.744. Predictions correlated well with observed 1-year and 2-year outcomes (judged by eye). The area under the time-dependent receiver operating characteristic curve at 12 months and 24 months was 0.876 and 0.838, respectively. The nomogram performed well in terms of both discrimination and calibration when applied to the validation cohort, and OS was significantly different between the two groups classified by nomogram score (log-rank p < .001). CONCLUSION: The validated nomogram provided useful prediction of OS, which can be offered for clinicians to improve their abilities to assess patient prognosis, to create clinical risk groups for informing treatment or for patient stratification by disease severity in clinical trials. IMPLICATIONS FOR PRACTICE: The high-grade neuroendocrine neoplasms of the digestive system are rare malignancies with great heterogeneity. An overall survival nomogram was developed and externally validated in this study. Two subgroups were classified by the nomogram score, and platinum-based chemotherapy may not bring clinical benefit for the low-risk patients.
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Neoplasias , Nomogramas , Estudos de Coortes , Humanos , Prognóstico , Curva ROC , Estudos RetrospectivosRESUMO
BACKGROUND: Gain-of-function mutations and overexpression of KIT are characteristic features of gastrointestinal stromal tumor (GIST). Dysregulation in miRNA expression may lead to KIT overexpression and tumorigenesis. METHODS: miRNA microarray analysis and real-time PCR were used to determine the miRNA expression profiles in a cohort of 69 clinical samples including 50 CD117IHC+/KITmutation GISTs and 19 CD117IHC-/wild-type GISTs. GO enrichment and KEGG pathway analyses were performed to reveal the predicted targets of the dysregulated miRNAs. Of the dysregulated miRNAs whose expression was inversely correlated with that of KIT miRNAs were predicted by bioinformatics analysis and confirmed by luciferase reporter assay. Cell counting kit-8 (CCK-8) and flow cytometry were used to measure the cell proliferation, cycle arrest and apoptosis. Wound healing and transwell assays were used to evaluate migration and invasion. A xenograft BALB/c nude mouse model was applied to investigate the tumorigenesis in vivo. Western blot and qRT-PCR were used to investigate the protein and mRNA levels of KIT and its downstream effectors including ERK, AKT and STAT3. RESULTS: Of the six miRNAs whose expression was inversely correlated with that of KIT, we found that miR-148b-3p was significantly downregulated in the CD117IHC+/KITmutation GIST cohort. This miRNA was subsequently found to inhibit proliferation, migration and invasion of GIST882 cells. Mechanistically, miR-148b-3p was shown to regulate KIT expression through directly binding to the 3'-UTR of the KIT mRNA. Restoration of miR-148b-3p expression in GIST882 cells led to reduced expression of KIT and the downstream effectors proteins ERK, AKT and STAT3. However, overexpression of KIT reversed the inhibitory effect of miR-148b-3p on cell proliferation, migration and invasion. Furthermore, we found that reduced miR-148b-3p expression correlated with poor overall survival (OS) and disease-free survival (DFS) in GIST patients. CONCLUSION: miR-148b-3p functions as an important regulator of KIT expression and a potential prognostic biomarker for GISTs.
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Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/patologia , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Regiões 3' não Traduzidas , Animais , Antagomirs/metabolismo , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/mortalidade , Tumores do Estroma Gastrointestinal/metabolismo , Tumores do Estroma Gastrointestinal/mortalidade , Humanos , Mesilato de Imatinib/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-kit/química , Proteínas Proto-Oncogênicas c-kit/genética , Fator de Transcrição STAT3/metabolismo , Taxa de SobrevidaRESUMO
Idesia polycarpa, belonging to the Flacourtiaceae family, is a tall deciduous tree, widely distributed in some Asian countries. It is famous for its high yield of fruit known as oil grape, which is rich of linoleic acid and linolenic acid, and so on. To provide evidences for its safe use as food, subchronic toxicity of I. polycarpa fruit oil and no observed adverse effect level were performed in male and female specific pathogen-free Wistar rats. Based on the Organization for Economic Co-operation and Development guidelines, the oil was orally administered to rats by gavage at 0, 1.0, 2.0, and 4.0mL/kg.bw/day for 90 days, followed by a 28-day recovery period. The results showed that no sign of oil-related toxicity, clinically or histologically, was observed in both male and female rats. Although there was a slight increase or decrease in some indicators such as hematology, serum chemistry, and so on, those changes were all within the normal ranges, and as presented in the 90-day study, the oil exhibited no toxic effect compared to the control rats. I. polycarpa might be a potential excellent and healthy vegetable oil resource.
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Frutas , Óleos de Plantas , Ratos Wistar , Testes de Toxicidade Subcrônica , Animais , Masculino , Feminino , Frutas/química , Ratos , Óleos de Plantas/toxicidade , Óleos de Plantas/administração & dosagem , Óleos de Plantas/química , Administração Oral , Nível de Efeito Adverso não ObservadoRESUMO
We demonstrate a pre-chirp and gain jointly managed Yb-fiber laser that drives simultaneous label-free autofluorescence-multiharmonic (SLAM) medical imaging. We show that a gain managed Yb-fiber amplifier produces high-quality compressed pulses when the seeding pulses exhibit proper negative pre-chirp. The resulting laser source can generate 43-MHz, 34-fs pulses centered at 1110â nm with more than 90-nJ energy. We apply this ultrafast source to SLAM imaging of cellular and extracellular components in various human tissues of intestinal adenocarcinoma, lung adenocarcinoma, and liver.
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Background: Currently, the reported links between olive oil intake and cardiovascular disease (CVD), cancer morbidity and mortality, and all-cause mortality are inconsistent. The aim of this meta-analysis is to study the reported correlations of olive oil intake with CVD, coronary heart disease (CHD), stroke and cancer incidence and mortality, and all-cause mortality. Methods: PubMed, Embase, and Web of Science were searched until March 7, 2024. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated by the random-effects model. Nonlinear dose-response relationships were modeled with restricted cubic splines. This study has been registered at PROSPERO (CRD42023419001). Results: Overall, 30 articles covering 2 710 351 participants were identified. Higher olive oil intake was linked with a reduced risk of CVD incidence (RR: 0.85; 95% CI: 0.77, 0.93), CHD incidence (RR: 0.85; 95% CI: 0.72, 0.99), CVD mortality (RR: 0.77; 95% CI: 0.67, 0.88), and all-cause mortality (RR: 0.85; 95% CI: 0.81, 0.89). For a 10 g d-1 increment of olive oil intake, the risk of CVD incidence, stroke incidence, CVD mortality, and all-cause mortality decreased by 7%, 5%, 8%, and 8%, respectively. No association was found between olive oil intake and cancer incidence and mortality. Nonlinear relationships between olive oil intake and CVD and all-cause mortality were observed, with a reduced risk from intakes ranging from 0 to 18 g d-1 and 0 to 22 g d-1, respectively. Conclusion: Our study found that high olive oil intake was related to a lower risk of CVD and CHD incidence and CVD mortality and all-cause mortality.
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Doenças Cardiovasculares , Neoplasias , Azeite de Oliva , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/epidemiologia , Incidência , Neoplasias/mortalidade , Neoplasias/epidemiologia , Estudos ProspectivosRESUMO
AIMS: To investigate the association of methylation risk score (MRS) and its interactions with environmental factors with type 2 diabetes mellitus (T2DM) risk. METHODS: We conducted a nested case-control study with 241 onset cases and 241 matched controls. Conditional logistic regression models were employed to identify risk CpG sites. Simple and weighted MRSs were constructed based on the methylation levels of ATP-binding cassette G1 gene, fat mass and obesity associated gene, potassium voltage-gated channel member 1 gene, and thioredoxin-interacting protein gene previously associated with T2DM to estimate the association of MRS with T2DM risk. Stratified analyses were used to investigate interactions between MRS and environmental factors. RESULTS: A total of 10 CpG loci were identified from the aforementioned genes to calculate MRS. After controlling for potential confounding factors, taking tertile 1 as reference, the odds ratios (ORs) and 95% confidence intervals (CIs) for T2DM of tertile 3 was 2.39 (1.36-4.20) for simple MRS and 2.59 (1.45-4.63) for weighted MRS. With per SD score increment in MRS, the OR (95% CI) was 1.66 (1.29-2.14) and 1.60 (1.24-2.08) for simple and weighted MRSs, respectively. J-curved associations were observed between both simple and weighted MRSs and T2DM risks. Additionally, multiplication interactions for smoking and hypertension with simple MRS on the risk of T2DM were found, similarly for smoking and obesity with weighted MRS on the risk of T2DM (all Pinteraction < .05). CONCLUSION: Elevated simple and weighted MRSs were associated with increased risk of T2DM. Environmental risk factors may influence the association between MRS and T2DM.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Estudos de Casos e Controles , Fatores de Risco , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/genética , MetilaçãoRESUMO
INTRODUCTION: The relationship between pregnancy loss and the risk of cardiovascular diseases (CVDs) remains a matter of debate. Our intention in conducting this meta-analysis was to analyze the relationship between miscarriage and stillbirth and risk of CVDs. METHODS: PubMed, Embase, and Web of Science were systematically searched up to May 30, 2023 for all relevant studies. The random-effects model was applied to estimate the pooled relative risks (RRs) and 95% confidence intervals (95% CIs). We evaluated RR estimates for the risk of CVDs with each additional miscarriage and stillbirth through generalized least squares regression. RESULTS: Twenty-three articles were incorporated into the meta-analysis. For women with a history of miscarriage, the pooled RRs for the risk of total CVDs, coronary heart disease (CHD), stroke, and total CVD deaths were 1.16 (95 % CI 1.10-1.22), 1.26 (1.12-1.41), 1.13 (1.03-1.24), and 1.20 (1.01-1.42), respectively. For women with a history of stillbirth, the pooled RRs for the risk of total CVDs, CHD, stroke, and total CVD deaths were 1.60 (1.34-1.89), 1.30 (1.12-1.50), 1.37 (1.06-1.78), and 1.95 (1.05-3.63), respectively. With each additional miscarriage, the risk increased for total CVDs (1.08, 1.04-1.13), CHD (1.08, 1.04-1.13), and stroke (1.05, 1.00-1.10). With each additional stillbirth, the risk increased for total CVDs (1.11, 1.03-1.21) and CHD (1.13, 1.07-1.19). CONCLUSION: This meta-analysis indicates that both miscarriages and stillbirths are related to a higher risk of total CVDs, CHD, stroke, and total CVD deaths. The risk of total CVDs and CHD increased with the number of miscarriages or stillbirths.
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Aborto Espontâneo , Doenças Cardiovasculares , Natimorto , Humanos , Natimorto/epidemiologia , Feminino , Aborto Espontâneo/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Gravidez , Fatores de RiscoRESUMO
Background: Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data. Methods: Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF. Results: For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram. Conclusions: The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram. Trial Registration: Clinicaltrials.gov Identifier: NCT04076631.
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Idesia polycarpa Maxim protein was used as a substrate to prepare a novel food packaging material with bioactive functions for encapsulating and extending the postharvest shelf life of sweet cherries. The film-forming solution was prepared from a mixture of Idesia polycarpa Maxim protein, glycerol, and gelatin, and was cast to form a film at room temperature and evaluated for mechanical, optical, structural, crystallinity, thermal properties, morphology, and antioxidant activity. Idesia polycarpa Maxim protein composite film solution was applied as an edible coating on sweet cherries and evaluated for changes in physical and biochemical parameters of sweet cherries in storage at 20°C and 50% relative humidity for 9 days. The results showed that the film tensile strength increased from 0.589 to 1.981 Mpa and the elongation at break increased from 42.555% to 58.386% with the increase of Idesia polycarpa Maxim protein concentration. And in the in vitro antioxidant assay, IPPF-4.0% was found to have the best antioxidant activity, with scavenging rates of 65.11% ± 1.19%, 70.74% ± 0.12%, and 90.96% ± 0.49% for DPPH radicals, ABTS radicals, and hydroxyl radicals, respectively. Idesia polycarpa Maxim protein coating applied to sweet cherries and after storage at 20°C and 50% relative humidity for 9 days, it was found that the Idesia polycarpa Maxim protein coating significantly reduced the weight loss (54.82% and 34.91% in the Control and Coating-2.5% groups, respectively) and the loss of ascorbic acid content (16.47% and 37.14% in the Control and Coating-2.5% groups, respectively) of the sweet cherries, which can effectively extend the aging of sweet cherry fruits and prolong their shelf life. The developed protein film of Idesia polycarpa Maxim with antioxidant activity can be used as a new food packaging material in the food industry.
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The artifacts in histology images may encumber the accurate interpretation of medical information and cause misdiagnosis. Accordingly, prepending manual quality control of artifacts considerably decreases the degree of automation. To close this gap, we propose a methodical pre-processing framework to detect and restore artifacts, which minimizes their impact on downstream AI diagnostic tasks. First, the artifact recognition network AR-Classifier first differentiates common artifacts from normal tissues, e.g., tissue folds, marking dye, tattoo pigment, spot, and out-of-focus, and also catalogs artifact patches by their restorability. Then, the succeeding artifact restoration network AR-CycleGAN performs de-artifact processing where stain styles and tissue structures can be maximally retained. We construct a benchmark for performance evaluation, curated from both clinically collected WSIs and public datasets of colorectal and breast cancer. The functional structures are compared with state-of-the-art methods, and also comprehensively evaluated by multiple metrics across multiple tasks, including artifact classification, artifact restoration, downstream diagnostic tasks of tumor classification and nuclei segmentation. The proposed system allows full automation of deep learning based histology image analysis without human intervention. Moreover, the structure-independent characteristic enables its processing with various artifact subtypes. The source code and data in this research are available at https://github.com/yunboer/AR-classifier-and-AR-CycleGAN.
Assuntos
Artefatos , Processamento de Imagem Assistida por Computador , Humanos , Imagens de Fantasmas , Processamento de Imagem Assistida por Computador/métodosRESUMO
To examine the independent and joint associations of dietary inflammation index (DII) and physical activity (PA) with mortality risk. We analyzed data for 20,165 study participants aged ≥ 18 from The Rural Chinese Cohort Study. The Cox proportional hazard model was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) of mortality associated with DII and PA. The dose-response association between DII and mortality risk was intuitively generated by the restricted cubic splines model. During the mean 5.03-year follow-up, a total of 1110 cases of all-cause mortality were identified. Compared with people in quartile 1 of DII, positive associations were found in quartile 4 for all-cause (HR 1.27; 95%CI 1.06-1.52), CVD (HR 1.45; 95%CI 1.09-1.91), and other mortality (HR 1.52; 95%CI 1.10-2.09), while a linear association was demonstrated. Compared with people of quartile 1 of DII and high intensity of PA, those with quartile 4 of DII and low intensity of PA had higher risk of all-cause (HR 1.96; 95%CI 1.50-2.56), CVD (HR 2.68; 95%CI 1.71-4.19), and other mortality (HR 1.83; 95%CI 1.19-2.83). A pro-inflammatory diet was significantly associated with increased risk of mortality and lower PA may strengthen the effect.
Assuntos
Doenças Cardiovasculares , Neoplasias , Humanos , Fatores de Risco , Estudos de Coortes , Causas de Morte , Seguimentos , Estudos Prospectivos , Dieta/efeitos adversos , Inflamação , Exercício FísicoRESUMO
Alcohol consumption remains inconsistently correlated with fracture risk, and a dose-response meta-analysis for specific outcomes is lacking. The objective of this study was to quantitatively integrate the data on the relationship between alcohol consumption and fracture risk. Pertinent articles were identified in PubMed, Web of Science, and Embase databases up to 20 February 2022. Combined RRs and 95% CIs were estimated by random- or fixed-effects models. Restricted cubic splines were used to model linear or nonlinear relationships. Forty-four articles covering 6,069,770 participants and 205,284 cases of fracture were included. The combined RRs and 95% CIs for highest compared with lowest alcohol consumption were 1.26 (1.17-1.37), 1.24 (1.13-1.35), and 1.20 (1.03-1.40) for total, osteoporotic, and hip fractures, respectively. A linear positive relationship between alcohol consumption and total fracture risk was detected (Pnonlinearity = 0.057); the risk was correlated with a 6% increase (RR, 1.06; 95% CI: 1.02, 1.10) per 14 g/d increment of alcohol consumption. J-shaped relationships of alcohol consumption with risk of osteoporotic fractures (Pnonlinearity < 0.001) and hip fractures (Pnonlinearity < 0.001) were found. Alcohol consumption of 0 to 22 g/d was linked to a reduced risk of osteoporotic fractures and hip fractures. Our findings show that any level of alcohol consumption is a risk factor for total fractures. Moreover, this dose-response meta-analysis shows that an alcohol consumption level of 0 to 22 g/d is related to a reduction in the risk of osteoporotic and hip fractures. The protocol was registered in the International Prospective Register of Systematic Reviews (CRD42022320623).