CD28null T cells in aging and diseases: From biology to assessment and intervention.

CD28null T cells, an atypical subset characterized by the loss of CD28 costimulatory molecule expression, exhibit functional variants and progressively expand with age. Moreover, T cells with these phenotypes are found in both typical and atypical humoral immune responses. Consequently, they accumulate during infectious diseases, autoimmune disorders, cardiovascular conditions, and neurodegenerative ailments. To provide an in-depth review of the current knowledge regarding CD28null T cells, we specifically focus on their phenotypic and functional characteristics as well as their physiological roles in aging and diseases. While uncertainties regarding the clinical utility remains, we will review the following two crucial research perspectives to explore clinical translational applications of the research on this specific T cell subset: 1) addressing the potential utility of CD28null T cells as immunological markers for prognosis and adverse outcomes in both aging and disease, and 2) speculating on the potential of targeting CD28null T cells as an interventional strategy for preventing or delaying immune aging processes and disease progression.

Vascular Aging: Assessment and Intervention.

Vascular aging represents a collection of structural and functional changes in a blood vessel with advancing age, including increased stiffness, vascular wall remodeling, loss of angiogenic ability, and endothelium-dependent vasodilation dysfunction. These age-related alterations may occur earlier in those who are at risk for or have cardiovascular diseases, therefore, are defined as early or premature vascular aging. Vascular aging contributes independently to cardio-cerebral vascular diseases (CCVDs). Thus, early diagnosis and interventions targeting vascular aging are of paramount importance in the delay or prevention of CCVDs. Here, we review the direct assessment of vascular aging by examining parameters that reflect changes in structure, function, or their compliance with age including arterial wall thickness and lumen diameter, endothelium-dependent vasodilation, arterial stiffness as well as indirect assessment through pathological studies of biomarkers including endothelial progenitor cell, lymphocytic telomeres, advanced glycation end-products, and C-reactive protein. Further, we evaluate how different types of interventions including lifestyle mediation, such as caloric restriction and salt intake, and treatments for hypertension, diabetes, and hyperlipidemia affect age-related vascular changes. As a single parameter or intervention targets only a certain vascular physiological change, it is recommended to use multiple parameters to evaluate and design intervention approaches accordingly to prevent systemic vascular aging in clinical practices or population-based studies.

Chinese expert consensus on assessment of cognitive impairment in the elderly.

Cognitive impairment is a term that refers to the impairment of one or more cognitive domains to varying degrees caused by a variety of reasons. It is under a high prevalence, many risk factors, complex etiology, and great harm to the elderly population. Early screening, diagnosis, and intervention for cognitive impairment in the elderly are of great importance. However, at present, the recognition rate of cognitive impairment for the elderly in China is low, the rate of missed diagnosis is high, and the evaluation is not standardized. This consensus integrates the commonly used cognitive function assessment scales in China and abroad, and aims to popularize the screening of cognitive impairment, standardize the evaluation methods and procedures of cognitive impairment in the elderly, and establish clinical diagnoses, interventions, and follow-up plans in a timely manner.

Expert consensus on clinical assessment and intervention of vascular aging in China (2018).

With the development of geriatric medicine, more and more reported research has found that as humans grow old, their blood vessels also age. Blood vessels are vital components of various organs. Vascular aging is an important physiological and pathological basis for the aging of organs and systems of the human body and is the common pathogenesis of various chronic diseases in the elderly. Early detection of vascular aging and the use of correct methods to delay and treat vascular aging are of great significance to prevent and control chronic diseases in the elderly and to deal with the increasingly serious problems of population aging. For this purpose, this consensus is formulated for use by geriatric doctors and related personnel.

Speckle tracking echocardiography assessment of global and regional contraction dysfunction in the mice model of pressure overload.

Speckle tracking echocardiography (STE) has been applied to the evaluation of cardiac contraction dysfunction. However, there were few studies on alteration of global and regional STE parameters in the process of myocardial hypertrophy and heart failure. In this study, STE was applied to evaluate the global and regional cardiac function under heart failure and hypertrophy in the mice model of pressure overload. Adult mice were subjected to mild or severe aortic banding with a 25 Gauge (G) or 27 G needle. After surgery, STE and conventional echocardiography were used in the sham group (n=10), mild trans-aortic banding (TAB) group (n=14) and severe TAB group (n=10) for 8 weeks. The results showed that the mice subjected to severe TAB showed a significant change in fractional shortening (FS), left ventricular (LV) mass, and left ventricular end diastolic diameter (LVEDD) (P<0.05 for each). Meanwhile, there were no significant differences in FS and LVEDD between the sham group and mild TAB group during the experimental procedures (P>0.05 for both). STE analysis revealed that longitudinal strain (LS) was significantly decreased in the severe TAB group as compared with the sham and mild TAB groups (P<0.05 for both) from the postoperative week 1. LS in the mild TAB group was reduced as compared to the sham group (P<0.05). Radial strain (RS) and circumferential strain (CS) were significantly decreased in the severe TAB group as compared to the sham group and the mild TAB group (P<0.05 for both) from the postoperative week 1 (P<0.05 for both). Compared to the sham group, CS in the mild TAB group maintained unchanged during the test period, and RS was reduced only on the postoperative week 6 (P<0.05). Finally, regional contraction dysfunction was analyzed in both hypertrophic and failing myocardium in longitudinal and radial directions. It was found that LS was largest in the apex region and RS was smallest in the apex region in the healthy and hypertrophic myocardium. It was also found that compared to the sham group, only base longitudinal strain in the mild TAB group was decreased. Each of regional strain in the severe TAB group was uniformly depressed in radial and longitudinal directions. It is concluded that STE has provided a non-invasive and highly feasible way to explore the global and regional contraction dysfunction in hypertrophic and heart failure myocardium in the murine model of pressure overload.

Ability of ambulatory ECG-based T-wave alternans to modify risk assessment of cardiac events: a systematic review.

BACKGROUND: Exercise-based spectral T-wave alternans (TWA) has been proposed as a noninvasive tool-identifying patients at risk of sudden cardiac death (SCD) and cardiac mortality. Prior studies have indicated that ambulatory electrocardiogram (AECG)-based TWA is an important alternative platform to exercise for risk stratification of cardiac events. This study sought to review data regarding 24-hour AECG-based TWA and to discuss its potential role in risk stratification of fatal cardiac events across a series of patient risk profiles. METHODS: Prospective clinical studies of the predictive value of AECG-based TWA obtained with daily activity published between January 1990 and November 2014 were retrieved. Major endpoints included composite endpoint of SCD, cardiac mortality, and severe arrhythmic events. RESULTS: Data were accumulated from 5 studies involving a total of 1,588 patients, including 317 positive and 1,271 negative TWA results. Compared with the negative group, positive group showed increased rates of SCD (hazard ratio [HR]: 7.49, 95% confidence interval [CI]: 2.65 to 21.15), cardiac mortality (HR: 4.75, 95% CI: 0.42 to 53.55), and composite endpoint (SCD, cardiac mortality, and severe arrhythmic events, HR: 5.94, 95% CI: 1.80 to 19.63). For the 4 studies evaluating TWA measured using the modified moving average method, the HR associated with a positive versus negative TWA result was 9.51 (95% CI: 4.99 to 18.11) for the composite endpoint. CONCLUSIONS: The positive group of AECG-based TWA has a nearly six-fold risk of severe outcomes compared with the negative group. Therefore, AECG-based TWA provides an accurate means of predicting fatal cardiac events.