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A newly described coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 2019 (COVID-19), has infected over 2.3 million people, led to the death of more than 160,000 individuals and caused worldwide social and economic disruption1,2. There are no antiviral drugs with proven clinical efficacy for the treatment of COVID-19, nor are there any vaccines that prevent infection with SARS-CoV-2, and efforts to develop drugs and vaccines are hampered by the limited knowledge of the molecular details of how SARS-CoV-2 infects cells. Here we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins that physically associated with each of the SARS-CoV-2 proteins using affinity-purification mass spectrometry, identifying 332 high-confidence protein-protein interactions between SARS-CoV-2 and human proteins. Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (of which, 29 drugs are approved by the US Food and Drug Administration, 12 are in clinical trials and 28 are preclinical compounds). We screened a subset of these in multiple viral assays and found two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the sigma-1 and sigma-2 receptors. Further studies of these host-factor-targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.
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Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/metabolismo , Reposicionamento de Medicamentos , Terapia de Alvo Molecular , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/metabolismo , Mapas de Interação de Proteínas , Proteínas Virais/metabolismo , Animais , Antivirais/classificação , Antivirais/farmacologia , Betacoronavirus/genética , Betacoronavirus/metabolismo , Betacoronavirus/patogenicidade , COVID-19 , Chlorocebus aethiops , Clonagem Molecular , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Avaliação Pré-Clínica de Medicamentos , Células HEK293 , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Imunidade Inata , Espectrometria de Massas , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Ligação Proteica , Biossíntese de Proteínas/efeitos dos fármacos , Domínios Proteicos , Mapeamento de Interação de Proteínas , Receptores sigma/metabolismo , SARS-CoV-2 , Proteínas Ligases SKP Culina F-Box/metabolismo , Células Vero , Proteínas Virais/genética , Tratamento Farmacológico da COVID-19RESUMO
AIM: To explore the relationship between proinflammatory diet, habitual salt intake and the onset of type 2 diabetes. METHODS: This prospective study was conducted among 171 094 UK Biobank participants who completed at least one 24-h dietary questionnaire and were free of diabetes at baseline. Participants were followed up until 1 March 2023 for type 2 diabetes incidence, with diagnosis information obtained from linked medical records. An Energy-adjusted Diet Inflammatory Index (E-DII) was calculated based on 28 food parameters. Habitual salt intake was determined through the self-reported frequency of adding salt to foods. The associations between E-DII, habitual salt intake and type 2 diabetes incidence were tested by the Cox proportional hazard regression model. RESULTS: Over a median follow-up period of 13.5 years, 6216 cases of type 2 diabetes were documented. Compared with participants with a low E-DII (indicative of an anti-inflammatory diet), participants with a high E-DII (indicative of a proinflammatory diet) had an 18% heightened risk of developing type 2 diabetes. The association between E-DII and type 2 diabetes tends to be linear after adjustment for major confounders. Participants with a proinflammatory diet and always adding salt to foods had the highest risk of type 2 diabetes incidence (hazard ratio 1.60, 95% confidence interval 1.32-1.94). CONCLUSIONS: Our findings indicate that a proinflammatory diet and higher habitual salt intake were associated with an increased risk of type 2 diabetes. These results support the public health promotion of an anti-inflammatory diet and reducing salt intake to prevent the onset of type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Dieta , Inflamação , Cloreto de Sódio na Dieta , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Coortes , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Dieta/efeitos adversos , Dieta/estatística & dados numéricos , Comportamento Alimentar , Seguimentos , Incidência , Inflamação/epidemiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Cloreto de Sódio na Dieta/efeitos adversos , Cloreto de Sódio na Dieta/administração & dosagem , Biobanco do Reino Unido , Reino Unido/epidemiologiaRESUMO
AIM: To investigate the associations between ketone bodies (KB) and multiple adverse outcomes including cardiovascular disease (CVD), chronic kidney disease (CKD) and all-cause mortality according to diabetes status. METHODS: This prospective study included 222 824 participants free from CVD and CKD at baseline from the UK Biobank. Total KB including ß-hydroxybutyrate, acetoacetate and acetone were measured by nuclear magnetic resonance. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between KB and adverse outcomes among participants with normoglycaemia, prediabetes and type 2 diabetes, respectively. RESULTS: During a mean follow-up of 14.1 years, 24 088 incident CVD events (including 17 303 coronary heart disease events, 5172 stroke events and 5881 heart failure [HF] events), 8605 CKD events and 15 813 deaths, were documented. Higher total KB significantly increased the risk of HF among participants with normoglycaemia (HR, 1.32 [95% CI, 1.17-1.49], per 10-fold increase in total KB) and prediabetes (1.35 [1.04-1.76]), and increased the risk of CKD among those with normoglycaemia (1.20 [1.09-1.33]). Elevated KB levels were associated with an increased risk of all-cause mortality across the glycaemic spectrum (1.32 [1.23-1.42] for normoglycaemia, 1.45 [1.24-1.71] for prediabetes and 1.47 [1.11-1.94] for diabetes). Moreover, a significant additive interaction between KB and diabetes status was observed on the risk of death (P = .009), with 4.9% of deaths attributed to the interactive effects. CONCLUSIONS: Our study underscored the variation in association patterns between KB and adverse outcomes according to diabetes status and suggested that KB could interact with diabetes status in an additive manner to increase the risk of mortality.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Corpos Cetônicos , Estado Pré-Diabético , Insuficiência Renal Crônica , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Prospectivos , Corpos Cetônicos/sangue , Estado Pré-Diabético/sangue , Estado Pré-Diabético/complicações , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/mortalidade , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/etiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/sangue , Reino Unido/epidemiologia , Adulto , Fatores de Risco , Seguimentos , Modelos de Riscos ProporcionaisRESUMO
Dengue illness can range from mild illness to life-threatening haemorrhage. It is an Aedes-borne infectious disease caused by the dengue virus, which has four serotypes. Each serotype acts as an independent infectious agent. The antibodies against one serotype confer homotypic immunity but temporary protection against heterotypic infection. Dengue has become a growing health concern for up to one third of the world's population. Currently, there is no potent anti-dengue medicine, and treatment for severe dengue relies on intravenous fluid management and pain medications. The burden of dengue dramatically increases despite advances in vector control measures. These factors underscore the need for a vaccine. Various dengue vaccine strategies have been demonstrated, that is, live attenuated vaccine, inactivated vaccine, DNA vaccine, subunit vaccine, and viral-vector vaccines, some of which are at the stage of clinical testing. Unfortunately, the forefront candidate vaccine is less than satisfactory, and its performance depends on serostatus and age factors. The lessons from clinical studies depicted ambiguity concerning the efficacy of dengue vaccine. Our study highlighted that viral structural heterogeneity, epitope accessibility, autoimmune complications, genetic variants, genetic diversities, antigen competition, virulence variation, host-pathogen specific interaction, antibody-dependent enhancement, cross-reactive immunity among Flaviviruses, and host-susceptibility determinants not only influence infection outcomes but also hampered successful vaccine development. This review integrates dengue determinants allocated necessities and challenges, which would provide insight for universal dengue vaccine development.
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Vacinas contra Dengue , Vírus da Dengue , Vacinas Virais , Animais , Humanos , Anticorpos Antivirais , Mosquitos Vetores , Desenvolvimento de VacinasRESUMO
The combination of immune checkpoint inhibitors and immunogenic cell death (ICD) inducers has become a promising strategy for the treatment of various cancers. However, its efficacy remains unmet because of the dense stroma and defective vasculatures in the tumor microenvironment (TME) that restricts the intratumoral infiltration of cytotoxic T lymphocytes (CTLs). Herein, cancer-associated fibroblasts (CAFs)-targeted nanoemulsions are tailored to combine the ICD induction and the TME reprogramming to sensitize checkpoint blockade immunotherapy. Melittin, as an ICD inducer and an antifibrotic agent, is efficiently encapsulated into the nanoemulsion accompanied by a nitric oxide donor to improve its bioavailability and tumor targeting. The nanoemulsions exhibited dual functionality by directly inducing direct cancer cell death and enhancing the tumoral immunogenicity, while also synergistically reprogramming the TME through reversing the activated CAFs, decreasing collagen deposition and restoring tumor vessels. Consequently, these nanemulsions successfully facilitated the CTLs infiltration and suppressing the recruitment of immunosuppressive cells. A combination of AE-MGNPs and anti-CTLA-4 antibody greatly elicited a striking level of antitumor T-cell response to suppress tumor growth in CAFs-rich colorectal tumor models. Our work emphasized the integration of the ICD induction with simultaneous modulation of the TME to enhance the sensitivity of patients to checkpoint blockade immunotherapy.
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Antineoplásicos , Neoplasias Colorretais , Neoplasias , Humanos , Microambiente Tumoral , Inibidores de Checkpoint Imunológico/farmacologia , Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Imunoterapia , Linhagem Celular TumoralRESUMO
Swimming microrobots that are actuated by multiple stimuli/fields display various intriguing collective behaviors, ranging from phase separation to clustering and giant number fluctuation; however, it is still chanllenging to achieve multiple responses and functionalities within one colloidal system to emulate high environmental adaptability and improved tasking capability of natural swarms. In this work, a weak ion-exchange based swarm is presented that can self-organize and reconfigure by chemical, light, and magnetic fields, showing living crystal, amorphous glass, liquid, chain, and wheel-like structures. By changing the frequency and strength of the rotating magnetic field, various well-controlled and fast transformations are obtained. Experiments show the high adaptability and functionality of the microrobot swarm in delivering drugs in confined spaces, such as narrow channels with turns or obstacles. The drug-carrying swarm exhibits excellent chemtherapy for Hela and CT26 cells due to the pH-enhanced drug release and locomotion. This reconfigurable microswarm provides a new platform for biomedical and environmental applications.
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BACKGROUND: Infectious diarrhea can lead to a considerable global disease burden. Thus, the accurate prediction of an infectious diarrhea epidemic is crucial for public health authorities. This study was aimed at developing an optimal random forest (RF) model, considering meteorological factors used to predict an incidence of infectious diarrhea in Jiangsu Province, China. METHODS: An RF model was developed and compared with classical autoregressive integrated moving average (ARIMA)/X models. Morbidity and meteorological data from 2012 to 2016 were used to construct the models and the data from 2017 were used for testing. RESULTS: The RF model considered atmospheric pressure, precipitation, relative humidity, and their lagged terms, as well as 1-4 week lag morbidity and time variable as the predictors. Meanwhile, a univariate model ARIMA (1,0,1)(1,0,0)52 (AIC = - 575.92, BIC = - 558.14) and a multivariable model ARIMAX (1,0,1)(1,0,0)52 with 0-1 week lag precipitation (AIC = - 578.58, BIC = - 578.13) were developed as benchmarks. The RF model outperformed the ARIMA/X models with a mean absolute percentage error (MAPE) of approximately 20%. The performance of the ARIMAX model was comparable to that of the ARIMA model with a MAPE reaching approximately 30%. CONCLUSIONS: The RF model fitted the dynamic nature of an infectious diarrhea epidemic well and delivered an ideal prediction accuracy. It comprehensively combined the synchronous and lagged effects of meteorological factors; it also integrated the autocorrelation and seasonality of the morbidity. The RF model can be used to predict the epidemic level and has a high potential for practical implementation.
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Diarreia/epidemiologia , Diarreia/microbiologia , Epidemias/prevenção & controle , Previsões/métodos , Modelos Estatísticos , Pressão Atmosférica , China/epidemiologia , Confiabilidade dos Dados , Humanos , Incidência , Morbidade , Estações do Ano , Tempo (Meteorologia)RESUMO
BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is an endemic communicable disease in China, accounting for 90% of total reported cases worldwide. In this study, the authors want to investigate the risk factors for HFRS in recent years to provide the prevention and control advices. METHODS: A community-based, 1:2 matched case-control study was carried out to investigate the risk factors for HFRS. Cases were defined as laboratory-confirmed cases that tested positive for hantavirus-specific IgM antibodies. Two neighbourhood controls of each case were selected by sex, age and occupation. Standardized questionnaires were used to collect information and identify the risk factors for HFRS. RESULTS: Eighty-six matched pairs were investigated in the study. The median age of the cases was 55.0 years, 72.09% were male, and 73.26% were farmers. In the multivariate logistic regression analysis, cleaning spare room at home (OR = 3.310, 95%CI 1.335-8.210) was found to be risk factor for infection; storing food and crops properly (OR = 0.279 95%CI 0.097-0.804) provided protection from infection. CONCLUSION: Storing food and crops properly seemed to be protective factor, which was important for HFRS prevention and control. More attention should be paid to promote comprehensive health education and behaviour change among high-risk populations in the HFRS endemic area.
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Febre Hemorrágica com Síndrome Renal/etiologia , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Estudos de Casos e Controles , China , Fazendeiros , Feminino , Vírus Hantaan/imunologia , Vírus Hantaan/patogenicidade , Febre Hemorrágica com Síndrome Renal/transmissão , Humanos , Imunoglobulina M/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Controle de RoedoresRESUMO
Cold atmospheric plasma (CAP) is a group of various chemical active species, such as ozone and nitric oxide, generated by working gas. CAP was demonstrated to have an effect on tissue regeneration and wound healing. We conducted this study to evaluate the efficacy and safety of CAP as a novel therapy for diabetic wounds in vitro and in vivo. The plasma consists of ionised helium gas that is produced by a high-voltage and high-frequency power supply. Eight-week-old male db/db mice and C57BL mice were treated with helium gas (control group), 90s' CAP (low-dose group), and 180s' CAP (high-dose group). Mice were treated and observed for 2 weeks. Skin samples from around the wound and blood samples were collected. Our in vitro analysis included scratch wound-healing assays by using human HaCaT immortalised human epidermal cells. After 14 days of treatment, CAP could obviously promote diabetic wound healing. Wound closure rates were significantly higher in the low-dose group and high-dose groups compared with the control group. Meanwhile, compared with the control group, the protein expression of IL-6, tumour necrosis factor-α, inducible nitric oxide synthase, and superoxide dismutase in two CAP groups significantly decreased, while the protein expression of vascular endothelial growth factor and transforming growth factor-ß in two CAP groups significantly increased (all P < .05); these data show good agreement with the change in mRNA level (all P < .05). In vitro, scratch wound-healing assays showed that plasma treatment could effectively ensure healing within 3 minutes of exposure (all P < .05). In addition, no difference was found in histological observations of normal skin and the level of serum alanine transaminase, aspartate aminotransferase, blood urea nitrogen, creatinine, and white blood cells among the CAP groups and control group. CAP treatment for 3 minutes every day improves wound healing in diabetic mice by suppressing inflammation, reducing oxidative stress, and enhancing angiogenesis, involving several proteins signalling, and it is safe for the liver and kidney.
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Pé Diabético/terapia , Gases em Plasma/uso terapêutico , Animais , Técnicas de Cultura de Células , Movimento Celular , Pé Diabético/etiologia , Pé Diabético/patologia , Modelos Animais de Doenças , Células Epidérmicas/fisiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , CicatrizaçãoRESUMO
Influenza activity is subject to environmental factors. Accurate forecasting of influenza epidemics would permit timely and effective implementation of public health interventions, but it remains challenging. In this study, we aimed to develop random forest (RF) regression models including meterological factors to predict seasonal influenza activity in Jiangsu provine, China. Coefficient of determination (R2) and mean absolute percentage error (MAPE) were employed to evaluate the models' performance. Three RF models with optimum parameters were constructed to predict influenza like illness (ILI) activity, influenza A and B (Flu-A and Flu-B) positive rates in Jiangsu. The models for Flu-B and ILI presented excellent performance with MAPEs <10%. The predicted values of the Flu-A model also matched the real trend very well, although its MAPE reached to 19.49% in the test set. The lagged dependent variables were vital predictors in each model. Seasonality was more pronounced in the models for ILI and Flu-A. The modification effects of the meteorological factors and their lagged terms on the prediction accuracy differed across the three models, while temperature always played an important role. Notably, atmospheric pressure made a major contribution to ILI and Flu-B forecasting. In brief, RF models performed well in influenza activity prediction. Impacts of meteorological factors on the predictive models for influenza activity are type-specific.
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Betainfluenzavirus , Regras de Decisão Clínica , Vírus da Influenza A , Influenza Humana/epidemiologia , Conceitos Meteorológicos , Clima Tropical , China/epidemiologia , Previsões , Temperatura Alta , Humanos , Modelos Biológicos , Vigilância em Saúde Pública , Análise de Regressão , Estações do AnoRESUMO
BACKGROUND: Hand, foot and mouth disease (HFMD) is a rising public health problem and has attracted considerable attention worldwide. The purpose of this study was to develop an optimal model with meteorological factors to predict the epidemic of HFMD. METHODS: Two types of methods, back propagation neural networks (BP) and auto-regressive integrated moving average (ARIMA), were employed to develop forecasting models, based on the monthly HFMD incidences and meteorological factors during 2009-2016 in Jiangsu province, China. Root mean square error (RMSE) and mean absolute percentage error (MAPE) were employed to select model and evaluate the performance of the models. RESULTS: Four models were constructed. The multivariate BP model was constructed using the HFMD incidences lagged from 1 to 4 months, mean temperature, rainfall and their one order lagged terms as inputs. The other BP model was fitted just using the lagged HFMD incidences as inputs. The univariate ARIMA model was specified as ARIMA (1,0,1)(1,1,0)12 (AIC = 1132.12, BIC = 1440.43). And the multivariate ARIMAX with one order lagged temperature as external predictor was fitted based on this ARIMA model (AIC = 1132.37, BIC = 1142.76). The multivariate BP model performed the best in both model fitting stage and prospective forecasting stage, with a MAPE no more than 20%. The performance of the multivariate ARIMAX model was similar to that of the univariate ARIMA model. Both performed much worse than the two BP models, with a high MAPE near to 40%. CONCLUSION: The multivariate BP model effectively integrated the autocorrelation of the HFMD incidence series. Meanwhile, it also comprehensively combined the climatic variables and their hysteresis effects. The introduction of the climate terms significantly improved the prediction accuracy of the BP model. This model could be an ideal method to predict the epidemic level of HFMD, which is of great importance for the public health authorities.
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Epidemias , Previsões/métodos , Doença de Mão, Pé e Boca/epidemiologia , China/epidemiologia , Confiabilidade dos Dados , Humanos , Incidência , Modelos Estatísticos , Redes Neurais de Computação , Estudos Prospectivos , Chuva , TemperaturaRESUMO
BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication of the central nervous system in elderly surgical patients. Structural MRI and arterial spin labelling (ASL) techniques found that the grey matter volume and cerebral perfusion in some specific brain areas are associated with the occurrence of POCD, but the results are inconsistent, and the predictive accuracy is low. We hypothesised that the combination of cortical grey matter volumetry and cerebral blood flow yield higher accuracy than either of the methods in discriminating the elderly individuals who are susceptible to POCD after abdominal surgery. MATERIALS AND METHODS: Participants underwent neuropsychological testing before and after surgery. Postoperative cognitive dysfunction (POCD) was defined as a decrease in cognitive score of at least 20%. ASL-MRI and T1-weighted imaging were performed before surgery. We compared differences in cerebral blood flow (CBF) and cortical grey matter characteristics between POCD and non-POCD patients and generated receiver operating characteristic curves. RESULTS: Out of 51 patients, 9 (17%) were diagnosed with POCD. CBF in the inferior frontal gyrus was lower in the POCD group compared to the non-POCD group (p < 0.001), and the volume of cortical grey matter in the anterior cingulate gyrus was higher in the POCD group (p < 0.001). The highest AUC value was 0.973. CONCLUSIONS: The combination of cortical grey matter volumetry and cerebral perfusion based on ASL-MRI has improved efficacy in the early warning of POCD to elderly abdominal surgical patients.
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Circulação Cerebrovascular , Substância Cinzenta , Imageamento por Ressonância Magnética , Complicações Cognitivas Pós-Operatórias , Humanos , Idoso , Masculino , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Circulação Cerebrovascular/fisiologia , Imageamento por Ressonância Magnética/métodos , Complicações Cognitivas Pós-Operatórias/diagnóstico por imagem , Complicações Cognitivas Pós-Operatórias/etiologia , Testes Neuropsicológicos , Idoso de 80 Anos ou mais , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Valor Preditivo dos Testes , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/diagnóstico por imagemRESUMO
AIM: This study aims to investigate the association of glycemia risk index (GRI), a novel composite metric derived from continuous glucose monitoring (CGM), with arterial stiffness in patients with type 2 diabetes. MATERIALS AND METHODS: A total of 342 adults with type 2 diabetes were enrolled between April and June 2023 from 11 communities in Shanghai, China. Medical examinations, including measurements of anthropometric parameters, blood pressure, and venous blood samples were conducted. Brachial-ankle pulse wave velocity (baPWV) was examined to evaluate arterial stiffness. All the participants underwent a 14 day CGM recording and GRI was calculated from the CGM data. RESULTS: The mean age was 70.3 ± 6.8 years, and 162 (47.4%) were male. Participants with a higher baPWV had significantly higher levels of GRI and hyperglycemia component (both P for trend < 0.05). Linear regression revealed the significant positive linear associations of the GRI with baPWV in unadjusted or adjusted models (All P < 0.05). In the multivariable logistic analysis, each increase in the GRI quartile was associated with a 1.30-fold (95% CI 1.01-1.68, P for trend < 0.05) higher prevalence of increased arterial stiffness after adjustment for age, sex, BMI, diabetes duration, current smoking status, blood pressure, and lipid profile. Subgroup analyses showed that the association between the GRI quartiles and increased arterial stiffness was stronger among participants with a diabetes duration ≥15 years (P for interaction = 0.014). CONCLUSION: Glycemia risk index assessed by continuous glucose monitoring is associated with increased arterial stiffness in type 2 diabetes.
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Glicemia , Diabetes Mellitus Tipo 2 , Rigidez Vascular , Humanos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Masculino , Feminino , Idoso , Glicemia/análise , China/epidemiologia , Fatores de Risco , Pessoa de Meia-Idade , Análise de Onda de Pulso , Índice Tornozelo-Braço , Automonitorização da Glicemia , Hiperglicemia/epidemiologia , Hiperglicemia/sangue , Hiperglicemia/complicações , Estudos Transversais , Seguimentos , Biomarcadores/sangueRESUMO
Background: Identification of individuals with prediabetes who are at high risk of developing diabetes allows for precise interventions. We aimed to determine the role of nuclear magnetic resonance (NMR)-based metabolomic signature in predicting the progression from prediabetes to diabetes. Methods: This prospective study included 13,489 participants with prediabetes who had metabolomic data from the UK Biobank. Circulating metabolites were quantified via NMR spectroscopy. Cox proportional hazard (CPH) models were performed to estimate the associations between metabolites and diabetes risk. Supporting vector machine, random forest, and extreme gradient boosting were used to select the optimal metabolite panel for prediction. CPH and random survival forest (RSF) models were utilized to validate the predictive ability of the metabolites. Results: During a median follow-up of 13.6 years, 2525 participants developed diabetes. After adjusting for covariates, 94 of 168 metabolites were associated with risk of progression to diabetes. A panel of nine metabolites, selected by all three machine-learning algorithms, was found to significantly improve diabetes risk prediction beyond conventional risk factors in the CPH model (area under the receiver-operating characteristic curve, 1 year: 0.823 for risk factors + metabolites vs 0.759 for risk factors, 5 years: 0.830 vs 0.798, 10 years: 0.801 vs 0.776, all p < 0.05). Similar results were observed from the RSF model. Categorization of participants according to the predicted value thresholds revealed distinct cumulative risk of diabetes. Conclusions: Our study lends support for use of the metabolite markers to help determine individuals with prediabetes who are at high risk of progressing to diabetes and inform targeted and efficient interventions. Funding: Shanghai Municipal Health Commission (2022XD017). Innovative Research Team of High-level Local Universities in Shanghai (SHSMU-ZDCX20212501). Shanghai Municipal Human Resources and Social Security Bureau (2020074). Clinical Research Plan of Shanghai Hospital Development Center (SHDC2020CR4006). Science and Technology Commission of Shanghai Municipality (22015810500).
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Progressão da Doença , Aprendizado de Máquina , Espectroscopia de Ressonância Magnética , Metabolômica , Estado Pré-Diabético , Humanos , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/sangue , Masculino , Metabolômica/métodos , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Espectroscopia de Ressonância Magnética/métodos , Adulto , Idoso , Diabetes Mellitus , Fatores de RiscoRESUMO
OBJECTIVES: Physical frailty has been found to increase the risk of multiple adverse outcomes including cardiovascular disease (CVD) in diabetic patients, but whether this could be modified by traditional risk factor control remains unknown. We aimed to explore the joint and interaction effects of frailty and traditional risk factor control on the risk of CVD. DESIGN: A population-based cohort study. SETTING AND PARTICIPANTS: We included 15,753 participants with type 2 diabetes at baseline from UK Biobank. MEASUREMENTS: Physical frailty was assessed by Fried criteria's frailty phenotype. The degree of risk factor control was determined by the numbers of the following factors controlled within the target range, including glycated hemoglobin, blood pressure, low-density lipoprotein cholesterol, smoking, and kidney condition. Incident CVD included coronary heart disease, stroke, or heart failure. Cox proportional hazard models were used to assess the individual and joint effects of frailty and risk factor control on the risk of CVD. RESULTS: After a median follow-up of 13.5 years, 1129 incident CVD events were observed. Compared with non-frailty, both prefrailty and frailty were significantly associated with increased risk of CVD (HR 1.22, 95% CI [1.13, 1.31] for pre-frailty and 1.70 [1.53, 1.90] for frailty). For the joint effects, participants with frailty and a low degree of risk factor control (control of 0-1 risk factors) had the highest risk of CVD (2.92 [2.04, 4.17]) compared to those with non-frailty and optimal risk factor control (control of 4-5 risk factors). Moreover, a significant additive interaction between frailty and risk factor control was observed, with around 3.8% of CVD risk attributed to the interactive effects. CONCLUSIONS: Both prefrailty and frailty were associated with a higher risk of CVD in participants with type 2 diabetes. Moreover, physical frailty could interact with the degree of risk factor control in an additive manner to increase the CVD risk.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Fragilidade , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Feminino , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/complicações , Fragilidade/complicações , Pessoa de Meia-Idade , Idoso , Reino Unido/epidemiologia , Estudos de Coortes , Fatores de Risco , Modelos de Riscos Proporcionais , IncidênciaRESUMO
Purpose: This study aimed to determine the associations of relative fat mass (RFM), a novel adiposity indicator, with the prevalence of non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) and compared the disease discriminative ability of RFM with other common adiposity indicators in the general Chinese population. Patients and Methods: This cross-sectional study consisted of 11,532 adult participants from the SPECT-China study (2014-2016). We included RFM and six other adiposity indicators, including body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), visceral adiposity index (VAI), and lipid accumulation product (LAP). Binary logistic regression analysis was used to assess the relationship between adiposity indicators and the prevalence of NAFLD and CVD. The receiver operating characteristic (ROC) curve was used to evaluate the ability to screen NAFLD and CVD. Results: After adjusting for confounding variables, RFM showed a strong association with the prevalence of NAFLD and CVD. In men, each 1-SD (standard deviation) increase in RFM was associated with more than 3-fold increased risk of NAFLD (OR: 4.33, 95% CI: 3.79-4.93) and 66% increased risk of CVD (OR: 1.66, 95% CI: 1.36-2.02); in women, per 1-SD increase in RFM was associated with about 4-fold increased risk of NAFLD (OR: 5.16, 95% CI: 4.62-5.77) and 26% increased risk of CVD (OR: 1.26, 95% CI: 1.08-1.47). ROC analysis showed that RFM and WHtR were the strongest predictors for CVD. Conclusion: RFM was significantly associated with prevalent NAFLD and CVD in Chinese adults and might be considered a simple tool for disease prediction. Further large longitudinal studies are needed to verify our findings.
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Objective: This study attempts to analyze the spatial clustering and spatial-temporal distribution characteristics of hepatitis E (HE) at the county (city and district) level in Jiangsu province to provide a scientific basis for the prevention and control of HE. Method: The information on HE cases reported in the Chinese Center for Disease Control and Prevention Information System from 2005 to 2020 was collected for spatial autocorrelation analysis and spatial-temporal clustering analysis. Result: From 2005 to 2020, 48,456 HE cases were reported in Jiangsu province, with an average annual incidence rate of 3.87/100,000. Male cases outnumbered female cases (2.46:1), and the incidence was highest in the 30-70 years of age group (80.50%). Farmers accounted for more than half of all cases (59.86%), and in terms of the average annual incidence, the top three cities were all in Zhenjiang city. Spatial autocorrelation analysis showed that Global Moran's I of HE incidence varied from 0.232 to 0.513 for the years. From 2005 to 2020, 31 counties (cities and districts) had high and statistically significant HE incidence, and two clustering areas were detected by spatial-temporal scanning. Conclusion: HE incidence in Jiangsu province from 2005 to 2020 was stable, with age and gender differences, regional clustering, and spatial-temporal clustering. Further investigation of HE clustering areas is necessary to formulate corresponding targeted prevention and control measures.
Assuntos
Hepatite E , Feminino , Humanos , Masculino , Povo Asiático/estatística & dados numéricos , Cidades/epidemiologia , Cidades/estatística & dados numéricos , Análise por Conglomerados , Fazendeiros/estatística & dados numéricos , Hepatite E/epidemiologia , Análise Espaço-Temporal , China/epidemiologia , Adulto , Pessoa de Meia-Idade , Idoso , IncidênciaRESUMO
Cancer-associated fibroblasts (CAFs) produce a critical tumor-promoting effect by cellular crosstalk with cancer cells and remodel the extracellular matrix (ECM) to form a protective physical barrier. The simple elimination of CAFs is not sufficient to govern the CAF-shaped aggressive tumor microenvironment (TME) because of the complexity of tumors. Herein, a CAF-targeted poly (lactic-co-glycolic acid) (PLGA) nanoemulsion is tailored to simultaneously deliver doxorubicin (DOX) and small interfering RNA (siRNA) targeting hepatocyte growth factor (HGF) for the combination of chemotherapy and gene therapy. The nanoemulsion (apt-Si/DNPs) shows a high specificity towards CAFs due to the aptamer modification and efficiently induces the apoptosis of CAFs, thus decreasing ECM deposition in the TME. Importantly, the delivered siRNA reduces the expression of the HGF in the remaining CAFs, which overcomes chemotherapy-induced upregulation of HGF mRNA and prevents the reproduction of CAFs through the autocrine HGF closed-loop. Owing to these synergetic effects, tumor proliferation, migration and invasion are prominently inhibited and tumor permeability is improved significantly. Overall, these results emphasize the potential of CAF-targeted combination treatments to inhibit tumor progression and metastasis, as well as overcome therapeutic resistance.
Assuntos
Fibroblastos Associados a Câncer , Neoplasias Colorretais , Nanopartículas , Humanos , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Microambiente Tumoral , Neoplasias Colorretais/patologia , RNA Interferente Pequeno/farmacologia , Proliferação de Células , Nanopartículas/uso terapêuticoRESUMO
Background: Over the past 70 years, China has advanced significantly in the prevention and treatment of infectious diseases while simultaneously undergoing a socioeconomic transformation, making it a useful source of data for analysing relationships between public health policy and the control of infectious diseases. Methods: We collected data on the incidence of notifiable infectious diseases and associated fatalities in Jiangsu province in southeast China from the Provincial Center for Disease Control and Prevention, Provincial Institute of Parasitic Diseases, and the Nationwide Notifiable Infectious Diseases Reporting Information System. We compared data from different historical periods using descriptive statistical methods, joinpoint regression, and correlation analysis. Results: During 1950-2022, 75 754 008 cases of 46 notifiable infectious diseases were reported in Jiangsu, with an average annual incidence was 1679.49 per 100 000 population and a fatality rate of 1.82 per 1000 persons. The incidence of classes A-B decreased (average annual percent change (AAPC) = -2.1) during the entire study period, while the incidence of class C increased (AAPC = 10.8) after 2004. The incidence of intestinal diseases (AAPC = -4.4) and vector-borne and zoonotic diseases (AAPC = -8.1) decreased rapidly, while the incidence of sexually transmitted and blood-borne diseases (AAPC = 1.8) increased. The number of medical and health institutions and the per capita gross domestic product correlated negatively with the annual incidence of diseases in classes A-B, but not with fatality rates. Conclusions: Although the annual incidence of many severe infectious diseases has decreased in Jiangsu since 1950, the incidence of sexually transmitted and blood-borne diseases increased. Socioeconomic growth and sustainable investment in health systems are associated with better control of infectious diseases.
Assuntos
Doenças Transmissíveis , Humanos , Animais , Incidência , Doenças Transmissíveis/epidemiologia , Zoonoses , China/epidemiologia , Fatores SocioeconômicosRESUMO
Background: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a conserved transcript with 8000 nt, is highly associated with malignancy of numerous cancer types. However, the function of MALAT1 plays in regulating the response to radiotherapy in colorectal cancer (CRC) remains unclear. Thus, the object of this study is to investigate the functions of MALAT1 in CRC radioresistance. Methods: First, the expression of MALAT1 in colon adenocarcinoma (COAD) was analyzed through the Cancer Genome Atlas (TCGA) database. Then, we detected the expression level of MALAT1 in tumor tissues and CRC cell lines and analyzed the relevance of MALAT1 and clinicopathological parameters. In the end, the effect of silencing MALAT1 on the radiosensitivity of CRC cells was investigated, and its potential mechanism was preliminarily illustrated. Results: The analysis of TCGA data showed that MALAT1 was closely related to the type of tumor, and high expression of MALAT1 was remarkably relevant to poor outcome. MALAT1 was highly expressed in CRC tissues and cell lines and related to tumor stages. Knockdown of MALAT1 could significantly suppress colony survival, proliferation, and migration and increase apoptosis, G2/M phase arrest, and formation of gamma-H2AX foci in HCT116, whether in combination with X-rays or not. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that the regulated proteins were principally enriched in the glycosaminoglycan degradation pathway after silencing MALAT1. Conclusion: Our results implied that MALAT1 was highly expressed in CRC and associated with tumor stage and prognosis. Silencing MALAT1 can increase HCT116 cell radiosensitivity, which may be potentially influenced by glycosaminoglycan degradation pathway.