DNA损伤在衰老相关疾病中的研究进展

DNA损伤是衰老相关疾病领域的研究热点, 可引起细胞周期停滞、凋亡, 加快个体衰老速度、增加衰老相关疾病的患病风险。本文将从细胞衰老和个体衰老两个层面阐述其与衰老之间的研究进展, 并综述其与衰老常见相关疾病(肿瘤、心血管疾病、阿尔茨海默病)及早衰综合征的关系, 为抗衰老研究和临床干预衰老相关疾病提供理论依据。     

Automatic Grading Assessments for Knee MRI Cartilage Defects via Self-ensembling Semi-supervised Learning with Dual-Consistency

Knee cartilage defects caused by osteoarthritis are major musculoskeletal disorders, leading to joint necrosis or even disability if not intervened at early stage. Deep learning has demonstrated its effectiveness in computer-aided diagnosis, but it is time-consuming to prepare a large set of well-annotated data by experienced radiologists for model training. In this paper, we propose a semi-supervised framework to effectively use unlabeled data for better evaluation of knee cartilage defect grading. Our framework is developed based on the widely-used mean-teacher classification model, by designing a novel dual-consistency strategy to boost the consistency between the teacher and student models. The main contributions are three-fold: (1) We define an attention loss function to make the network focus on the cartilage regions, which can both achieve accurate attention masks and boost classification performance simultaneously; (2) Besides enforcing the consistency of classification results, we further design a novel attention consistency mechanism to ensure the focusing of the student and teacher networks on the same defect regions; (3) We introduce an aggregation approach to ensemble the slice-level classification outcomes for deriving the final subject-level diagnosis. Experimental results show that our proposed method can significantly improve both classification and localization performances of knee cartilage defects. Our code is available on https://github.com/King-HAW/DC-MT.     

Feasibility,acceptability and preliminary impact of mindfulness-based yoga among Hispanic/Latinx adolescents

Background: The Hispanic/Latinx population constitutes the fastest growing ethnic/racial minority group in the United States (U.S.). Compared to their non-Hispanic/Latinx White counterparts, Hispanic/Latinx youth experience more depression and anxiety, and have more unmet mental health needs (88% vs 76%). Emerging research supports the psychological and physical benefits of mind-body awareness training to enhance well-being and mental health, but almost no studies have recruited ethnic/racial minority samples. Purpose: The current study examined the feasibility, acceptability and preliminary impact of a mindfulness-based yoga program among Hispanic/Latinx public high school students. Procedures: Participants (N = 187) were recruited from a local public high school in a large multi-ethnic urban school district in the Southeast U.S. and participated in 6 weekly hour-long sessions of mindfulness-based yoga. Participants completed assessments at pretest and one month after program completion. Main Findings: The sample was predominantly Hispanic/Latinx (95%) and female (64%), on average 15.2 years old (SD = 1.3), and 51% were born outside the U.S. Participants reported on average a 14.2% reduction in depressive symptoms (pretest mean = 5.51, posttest mean = 4.73, p = .032, Cohen's d = 0.2), a 14.9% reduction in anxiety symptoms (pretest mean = 9.90, posttest mean = 8.42, p = .005, Cohen's d = 0.2), and a 21.9% reduction in stress (pretest mean = 9.66, posttest mean = 7.54, p < .001, Cohen's d = 0.5). Conclusion: These findings provide support for the effectiveness of a mindfulness-based yoga program for Hispanic/Latinx adolescents, a medically underrepresented group experiencing significant mental health disparities.     

Mendelian randomization as a tool to gain insights into the mosaic causes of autoimmune diseases

Autoimmune diseases (ADs) are a broad range of disorders which are characterized by long-term inflammation and tissue damage arising from an immune response against one's own tissues. It is now widely accepted that the causes of ADs include environmental factors, genetic susceptibility and immune dysregulation. However, the exact etiology of ADs has not been fully elucidated to date. Because observational studies are plagued by confounding factors and reverse causality, no firm conclusions can be drawn about the etiology of ADs. Over the years, Mendelian randomization (MR) analysis has come into focus, offering unique perspectives and insights into the etiology of ADs and promising the discovery of potential therapeutic interventions. In MR analysis, genetic variation (alleles are randomly dispensed during meiosis, usually irrespective of environmental or lifestyle factors) is used instead of modifiable exposure to explore the link between exposure factors and disease or other outcomes. Therefore, MR analysis can provide a valuable method for exploring the causal relationship between different risk factors and ADs when its inherent assumptions and limitations are fully considered. This review summarized the recent findings of MR in major ADs, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), and type 1 diabetes mellitus (T1DM), focused on the effects of different risk factors on ADs risks. In addition, we also discussed the opportunities and challenges of MR methods in ADs research.     

Perivascular fat attenuation for predicting adverse cardiac events in stable patients undergoing invasive coronary angiography

BackgroundInflammation surrounding the coronary arteries can be non-invasively assessed using pericoronary adipose tissue attenuation (PCAT). While PCAT holds promise for further risk stratification of patients with low coronary artery disease (CAD) prevalence, its value in higher risk populations remains unknown.MethodsCORE320 enrolled patients referred for invasive coronary angiography with known or suspected CAD. Coronary computed tomography angiography (CCTA) images were collected for 381 patients for whom clinical outcomes were assessed 5 years after enrollment. Using semi-automated image analysis software, PCAT was obtained and normalized for the right coronary (RCA), left anterior descending (LAD), and left circumflex arteries (LCx). The association between PCAT and major adverse cardiovascular events (MACE) during follow up was assessed using Cox regression models.ResultsThirty-seven patients were excluded due to technical failure. For the remaining 344 patients, median age was 62 (interquartile range, 55–68) with 59% having ≥1 coronary artery stenosis of ≥50% by quantitative coronary angiography. Mean attenuation values for PCAT in RCA, LAD, and LCx were ?74.9, ?74.2, and ?71.2, respectively. Hazard ratios and 95% confidence intervals (CI) for normalized PCAT in the RCA, LAD, and LCx for MACE were 0.96 (CI: 0.75–1.22, p ?= ?0.71), 1.31 (95% CI: 0.96–1.78, p ?= ?0.09), and 0.98 (95% CI: 0.78–1.22, p ?= ?0.84), respectively. For death, stroke, or myocardial infarction only, hazard ratios were 0.68 (0.44–1.07), 0.85 (0.56–1.29), and 0.57 (0.41–0.80), respectively.ConclusionsIn patients referred for invasive coronary angiography with suspected CAD, PCAT did not predict MACE during long term follow up. Further studies are needed to understand the relationship of PCAT with CAD risk.     

Modern Medicine: Ideas and Advances

Considering the limitations of medical science and the risks associated with medical treatments, we need to re-examine the connotation of medical science from the perspective of philosophy. Medical science is the natural expression of human kindness and human nature of rescuing the dying and healing the wounded. It is a combination of the natural sciences, social sciences, and humanities. From the perspectives of medical philosophy and humanistic care, this article expounds the concepts and ideas of evidence-based, translational, and precision medicine in modern medicine and emphasizes the importance of avoiding new technical bureaucracy, paying attention to achieving a holistic view and systematic understanding, and avoiding biases in development because of the loss of the humanistic spirit in modern medical practice.     

An observational study evaluating the impact on prostate patient outcomes and experiences when radiation therapists use a standard grading system tool to assess and document treatment-related toxicities and interventions

Background/PurposeMen undergoing radiation therapy (RT) treatment for prostate cancer (PC) often experience acute urinary, bowel, sexual, and hormonal toxicities. Timely screening, management, and documentation of these toxicities is an integral part of clinician practice, ensuring patients receive the care they require. Various screening tools, completed by either the patient or the clinician, are available, which allow clinicians to collect and respond to these toxicity outcomes; however there is a paucity of literature regarding the effective use and timing of these tools during RT treatment. This study aims to evaluate the feasibility of conducting comprehensive toxicity screening and symptom management using a toxicity screening tool in one of the busiest RT departments in Canada. Specifically, the use of a toxicity screening tool and its effect on the quality of toxicity documentation, operational impact, and patient reported outcomes (PRO).Methods90 consented patients were allocated to either the structured or non-structured arm. Patients in the structured arm were assessed weekly by radiation therapists for 13 toxicities across four domains (bladder, bowel, hormonal, and sexual), using an in-house developed structured questionnaire, known as the Grid, to complete the National Cancer Institute's Common Toxicity Criteria for Adverse Events v3 (CTCAEv3). Patients in the non-structured arm were assessed and had free text clinical documentation charted according to current department policy. The Expanded Prostate Cancer Index Composite (EPIC), a PRO tool to evaluate patient function and bother after prostate cancer treatment, was completed by all study patients on a weekly basis. Statistical analysis compared documentation completeness, EPIC scores, patient satisfaction, and operational impact between study arms, as well as evaluated optimal timing of toxicity assessments.ResultsAssessment of the non-structured arm for completeness revealed an inconsistent and insufficient amount of documentation for the bladder and bowel domains. As for both the sexual and hormonal domains, documentation was largely absent. There was no difference in EPIC scores and patient satisfaction scores between the structured arm and the non-structured arm. Evaluation of the timing of PROs showed significant week to week change for the bladder and bowel toxicities, but not the sexual and hormonal toxicities. Finally, the use of the Grid revealed no significant impact on daily operations, only increasing average treatment times by seven seconds, and did not create any additional workload for the oncologists.ConclusionsUse of the Grid increased documentation completeness without negatively impacting clinical flow or operations, despite the fact that PROs were not improved. Based on EPIC PRO scores, bladder and bowel toxicities should be evaluated on a weekly basis during RT treatment, while sexual and hormonal toxicities need only be evaluated monthly.