英国医学科学院

INTRODUCTION/OBJECTIVE:Chronic inflammation is the basis of various diseases, including inflammatory bowel disease, neurodegenerative diseases, and cardiometabolic disorders. NLRP3 is a key player in controlling Interleukin-1β (IL-1β) and Interleukin-18 (IL-18) maturation and pyroptosis via its NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. This review will assess the mechanistic and therapeutic opportunity of resveratrol in restraining the NLRP3 inflammasome activation. METHODS:A search of experimental and preclinical studies examining the impact of resveratrol on oxidative stress, inflammatory signaling, mitochondrial activity, and inflammasome activation in various disease models was performed. RESULTS:Resveratrol reduces oxidative stress by regulating reactive oxygen species-mediated nuclear factor erythroid 2-related factor 2 signaling and suppressing toll-like receptor 4 (TLR4) /nuclear factor kappa B signaling (NF-κB). It maintains mitochondrial integrity by activating sirtuin 1 and AMP-activated protein kinase signalling. In models of acute lung injury, bronchitis, diabetic nephropathy, and neurodegeneration, resveratrol can suppress the expression of NLRP3, caspase-1, and IL-1β, promote autophagy, and prevent dopaminergic neurons through the PINK1/Parkin/NLRP3 pathway. Additionally, it enhances intestinal barrier integrity in dextran sulfate sodium-induced colitis and suppresses inflammasome-mediated inflammation. DISCUSSION:These results suggest that resveratrol regulates the priming and activation stages of NLRP3 inflammasome signaling by inhibiting oxidative stress, mitochondrial dysfunction, and inflammatory cascades based on redox signaling. Nanoparticle preparations and structural analogs, such as pterostilbene, improve stability, bioavailability, and specific delivery. CONCLUSION:Resveratrol is a potential natural therapeutic agent for managing NLRP3 inflammasomemediated inflammation, and its efficacy is enhanced when administered in optimal formulations and combined with conventional anti-inflammatory agents.

Introduction: Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability worldwide, with smoking being the primary contributor. This study aims to assess the temporal and spatial trends in the burden of smoking-attributable COPD from 1990 to 2021 and project future trajectories, providing insights for COPD prevention strategies. Methods: The data were sourced from the Global Burden of Disease (GBD) 2021 database, incorporating estimates and uncertainty intervals (UI) for deaths, disability-adjusted life years (DALYs), and age-standardized rates (ASRs) of smoking-attributable COPD across 204 countries and regions worldwide. Estimated annual percentage change (EAPC), frontier analysis, decomposition analysis, and Bayesian age-period-cohort (BAPC) modeling were used to evaluate temporal trends, development-related gaps, drivers of change, and future burden. Results: From 1990 to 2021, global smoking-attributable COPD showed a divergence between rising absolute burden and declining ASRs. Deaths increased from 10,538 (95% UI: 8,724-12,339) hundred to 13,350 (95% UI: 10,533-15,966) hundred, and DALYs rose from 23,601 (95% UI: 19,648-27,495) thousand to 27,795 (95% UI: 22,234-32,884) thousand, whereas ASRs declined across most regions. The steepest declines in ASRs were observed in High-middle SDI regions, whereas Middle and Low-middle SDI regions carried the greatest absolute burden in 2021. Males consistently bore a higher burden than females. DALYs increased with age, peaking at 70-74 years. Ageing and population growth were the main contributors to the rise in DALYs, while epidemiological changes had a negative effect. By 2040, global ASMR and ASDR are projected to decline to 11.62 and 240.32 per 100,000 population, respectively. Conclusion: Despite global progress in reducing the ASRs of smoking-related COPD, the absolute burden continues to rise. Further progress may require sustained tobacco control, earlier detection, and improved long-term COPD care, especially in settings where demographic pressures offset epidemiological gains.

Background With the aim of making it easier for researchers to produce policy-relevant research, the UK Government now requires all departments and arms-length bodies to publish annually-updated statements of their evidence needs, called ‘Areas of Research Interest’ (ARIs). We describe how ARIs are produced, and how they are used to support this aim. Aims and objectives In this paper we offer a description of ARIs and their development by UK governmental departments, and an assessment of how different stakeholders, including academia and funders, have responded to or otherwise used the ARIs. Key conclusions ARIs are a mechanism for organisations to share their research interests with external audiences in the form of a published document. In addition to this primary aim, they also have a much broader set of uses, including connecting departments with each other and helping intermediaries shape engagement plans. All groups would benefit from more robust evidence to choose effective engagement mechanisms, and more can be done to make the ARIs discoverable and useable. Overall, the ARIs are a useful tool to illuminate, and begin to connect different parts of the research-policy system.

Yujia Zhang,1 Mengyi Dou,2 Fengqin Ding,3 Jingjing Yan,4 Yixin Li,5 Jing Tian,6,7 Ruihua Wang21Clinical Medicine Program, The First Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of China; 2Department of Cardiology, Changzhi People’s Hospital, Changzhi, Shanxi, 046000, People’s Republic of China; 3Jinzhong Center for Disease Control and Prevention, Jinzhong, Shanxi, 030604, People’s Republic of China; 4Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of China; 5Academy of Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of China; 6Department of Cardiology, The 1st Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of China; 7Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, Taiyuan, Shanxi, 030001, People’s Republic of ChinaCorrespondence: Ruihua Wang, Email 308609690@qq.comBackground: Prediction models for mortality risk in patients with chronic heart failure (CHF) have traditionally relied on static admission data, which restricts capturing disease dynamics. Longitudinal follow-up data were used to develop a dynamic model to improve accuracy and provide evidence for tailored interventions.Methods: We enrolled 1,333 CHF patients from 3 Shanxi centres. Data included CHF patient-reported outcome (PRO) measures (CHF-PROM), lifestyle, medications, and prognosis. Endpoint: all-cause mortality. Using sequential data, we developed Gated Recurrent Units (GRU), Long Short-Term Memory (LSTM), Multi-layer Perceptron (MLP), and Logistic Regression (LR) for 3-year risk. Performance assessed by area under the receiver operating characteristic curve (AUC), accuracy, true negative rate (TNR), true positive rate (TPR), Brier score, and F1-score. Temporal Shapley Additive exPlanations (TimeSHAP) provided interpretability, and a web tool built.Results: Among models tested, the GRU model demonstrated strongest predictive accuracy, with performance steadily increasing as follow-up progressed. By 24 months, the GRU-based model attained its peak predictive performance, yielding an AUC of 0.765 (95% confidence interval [CI]: 0.761– 0.768), an F1-score of 0.537 (95% CI: 0.531– 0.542), and a Brier score of 0.208 (95% CI: 0.199– 0.216). TimeSHAP indicated that physical condition, appetite, sleep, physical independence, and anxiety within the CHF-PROM, together with age and New York Heart Association Functional Classification functional class, were key predictors of 3-year all-cause mortality in patients with CHF.Conclusion: PRO data from multiple follow-ups, combined with a model constructed using GRU, provides promising tool for predicting mortality risk in patients with chronic heart failure (CHF). The self-developed web-based decision support system allows users to calculate risk scores simply by entering patient information.Trial Registration: Study registered with the China Clinical Trial Registry [identifier: ChiCTR2100043337]. Experimental registration date is February 11, 2021.Keywords: chronic heart failure, patient-reported outcomes, recurrent neural network, prognosis model

Bones are mineralized connective tissue that provides to body anti-gravity support, enables movement with the help of muscles, and protects internal organs. Individual skeletal quality, as a result of genetic, hormonal, and external factors, such as nutrition, physical activity and others, is achieved during the period of growth and development. Peak bone mass is attained by the end of the second decade of life and is maintained until age 40–50, then gradually decreases without the possibility of rebuilt. It is therefore clear that the lack of adequate bone mass building during the development period, in addition to the immediate consequences, represents a high risk of osteoporosis and its complications in later life, especially in old age. The purpose of this article is to review the importance of optimal calcium, phosphorus, and vitamin D balance and adequate physical activity during growth and development in achieving maximizing peak bone mass.