Within the last few years, it has become evident that LPS-preconditioned mesenchymal stromal cells (LPS pre-MSCs) show enhanced paracrine effects, including increased trophic support and improved regenerative and repair properties. MSCs may release large amounts of exosomes for cell-to-cell communication and maintain a dynamic and homeostatic microenvironment for tissue repair. The present study assesses the therapeutic efficacy and mechanisms of LPS-preconditioned MSC-derived exosomes (LPS pre-Exo) for chronic inflammation and wound healing. We extracted exosomes from the supernatant of LPS pre-MSCs using a gradient centrifugation method. In vitro, THP-1 cells were cultured with high glucose (HG, 30 mM) as an inflammatory model and treated with LPS pre-Exo for 48 h. The expression of inflammation-related cytokines was detected by real-time RT-PCR, and the distribution of macrophage subtype was measured by immunofluorescence. Next, the miRNA expression profiles of LPS pre-Exo were evaluated using miRNA microarray analysis. The molecular signaling pathway responsible for the regenerative potential was identified by western blotting. In vivo, we established a cutaneous wound model in streptozotocin-induced diabetic rats, and LPS pre-Exo were injected dispersively into the wound edge. The curative effects of LPS pre-Exo on inflammation and wound healing were observed and evaluated. LPS pre-Exo have a better ability than untreated MSC-derived exosomes (un-Exo) to modulate the balance of macrophages due to their upregulation of the expression of anti-inflammatory cytokines and promotion of M2 macrophage activation. Microarray analysis of LPS pre-Exo identified the unique expression of let-7b compared with un-Exo, and the let-7b/TLR4 pathway served as potential contributor to macrophage polarization and inflammatory ablation. Further investigation of the mechanisms that control let-7b expression demonstrated that a TLR4/NF-κB/STAT3/AKT regulatory signaling pathway plays a critical role in the regulation of macrophage plasticity. Knockdown of AKT in THP-1 cells similarly abolished the immunomodulatory effect of LPS pre-Exo. In vivo, LPS pre-Exo greatly alleviated inflammation and enhanced diabetic cutaneous wound healing. LPS pre-Exo may have improved regulatory abilities for macrophage polarization and resolution of chronic inflammation by shuttling let-7b, and these exosomes carry much immunotherapeutic potential for wound healing.

Background: The Pittsburgh Sleep Quality Index (PSQI) is a widely used self-report questionnaire that measures general sleep quality in general populations. However, its psychometric properties have yet to be thoroughly examined in longevous persons. Objectives: This study aimed to explore the reliability, validity and factor structure of the Chinese-language version of the PSQI in community-dwelling centenarians. Methods: A total of 958 centenarians (mean age = 102.8 years; 81.8% females) recruited from 18 regions in Hainan, China, completed the PSQI scale. Cronbach’s alpha coefficient was used to measure the internal consistency. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed to explore the validity and factor structure of the PSQI in this sample. Correlations between the global PSQI score and physical function, depression symptoms, self-reported health status and subjective well-being were used to assess divergent validity. Results: The Cronbach’s α coefficient of the PSQI was 0.68, and it increased to 0.78 after two components (medication use and daytime dysfunction) were removed. The Spearman correlation coefficients of the PSQI score with each component were statistically significant (P<0.01). EFA yielded a two-factor structure model of the original PSQI-7 and a one-factor structure model of the simplified PSQI-5. The one-factor model with five components (χ²/df =1.59, CFI=0.99, RMSEA=0.03) fit the data well and had good configural invariance across demographic characteristics (0.53<_Δχ²0.05). Conclusions: The original PSQI showed acceptable applicability in Chinese community-dwelling centenarians, and its psychometric characteristics moderately improved after sleeping medication and daytime dysfunction were removed. Further validation studies on PSQI are needed among centenarians from varied backgrounds.

Due to the continued high incidence and mortality rate worldwide, there is still a need to develop new strategies for the prevention, diagnosis and treatment of cardiovascular diseases (CVDs). Proper cardiovascular function depends on the coordinated interplay and communication between cardiomyocytes and noncardiomyocytes. Extracellular vesicles (EVs) are enclosed in a lipid bilayer and represent a significant mechanism for intracellular communication. By containing and transporting various bioactive molecules, such as micro-ribonucleic acids (miRs) and proteins, to target cells, EVs impart favourable, neutral or detrimental effects on recipient cells, such as modulating gene expression, influencing cell phenotype, affecting molecular pathways and mediating biological behaviours. EVs can be released by cardiovascular system-related cells, such as cardiomyocytes, endotheliocytes, fibroblasts, platelets, smooth muscle cells, leucocytes, monocytes and macrophages. EVs containing miRs and proteins regulate a multitude of diverse functions in target cells, maintaining cardiovascular balance and health or inducing pathological changes in CVDs. On the one hand, miRs and proteins transferred by EVs play biological roles in maintaining normal cardiac structure and function under physiological conditions. On the other hand, EVs change the composition of their miR and protein cargoes under pathological conditions, which gives rise to the development of CVDs. Therefore, EVs hold tremendous potential to prevent, diagnose and treat CVDs. The current article reviews the specific functions of EVs in different CVDs.

Cognitive decline is a growing public health concern. However, presently, only a few large-scale studies are available on the prevalence of cognitive decline worldwide, and the relationship between nutrition and cognitive decline remains unclear and requires further investigation, especially among Chinese centenarians and oldest-old adults. This study aimed to assess the prevalence of cognitive decline among Chinese centenarians and oldest-old adults, its associated factors, and explore a possible connection with nutrition, to provide new directions for the prevention of cognitive decline in Chinese centenarians and oldest-old adults. Based on the China Hainan Centenarian Cohort Study (CHCCS), a household survey was conducted among all the centenarians and oldest-old adults residing in 16 cities and counties of Hainan province from June 2014 to June 2016. This study included 946 centenarians and oldest-old adults (412 and 534, respectively). Cognitive function was measured using the mini-mental state examination (MMSE). The total prevalence of cognitive decline was 76·6% (725 participants). Centenarians had a significantly higher prevalence of cognitive decline compared to oldest-old adults [359 centenarians (87·1%) vs. 366 oldest-old adults (68·5%)]. Centenarians and oldest-old adults with cognitive decline had significantly lower prognostic nutritional index (PNI) and mini nutrition assessment-short form (MNA-SF) than those without cognitive decline (P < 0·05). Multivariate logistic regression analyses showed that participants with higher PNI and MNA-SF were less likely to have cognitive decline. Multivariate linear regression analyses showed that PNI and MNA-SF were positively associated with MMSE (P < 0·05). Malnutrition was positively associated with cognitive decline among Chinese centenarians and oldest-old adults. It is therefore important for clinicians and community health workers to pay attention to malnutrition in these populations and provide supplemental nutrients to prevent cognitive decline. This work was supported by grants from the National Natural Science Foundation of China (81900357, 81903392, 81941021, 81901252, 82001476, 81802804, 81801251), the Military Medical Science and Technology Youth Incubation Program (20QNPY110, 19QNP060), the Excellent Youth Incubation Program of Chinese People's Liberation Army General Hospital (2020-YQPY-007), the Military Medicine Youth Program of Chinese People's Liberation Army General Hospital (QNF19069, QNF19068), the National Key R&D Program of China (2018YFC2000400), the National S&D Resource Sharing Service Platform Project of China (YCZYPT[2018]07), the Innovation Platform for Academinicians of Hainan Province, the Hainan Major Scientific and Technological Cooperation Project (2016KJHZ0039), the China Postdoctoral Science Foundation funded project (2019M650359, 2020M682816, 2021T140298), the Medical Big Data R&D Project of Chinese People's Liberation Army General Hospital (MBD2018030), the National Geriatric Disease Clinical Medicine Research centre Project (NCRCG-PLAGH-2017-014), the Central Health Care Scientific Research Project (W2017BJ12), the Hainan Medical and Health Research Project (16A200057), the Sanya Medical and Health Science and Technology Innovation Project (2016YW21, 2017YW22, 2018YW11), and the Clinical Scientific Research Supporting Fund of Chinese People's Liberation Army General Hospital (2017FC-CXYY-3009).

Heart failure (HF) with preserved ejection fraction (HFpEF) is a leading cause of hospitalizations and mortality when diagnosed at the age of ≥ 65 years. HFpEF represents multifactorial and multisystemic syndrome and has different pathophysiology and phenotypes. Its diagnosis is difficult to be established based on left ventricular ejection fraction and may benefit from individually tailored approaches, underlying age-related changes and frequent comorbidities. Compared with the rapid development in the treatment of heart failure with reduced ejection fraction, HFpEF presents a great challenge and needs to be addressed considering the failure of HF drugs to improve its outcomes. Further extensive studies on the relationships between HFpEF, aging, and comorbidities in carefully phenotyped HFpEF subgroups may help understand the biology, diagnosis, and treatment of HFpEF. The current review summarized the diagnostic and therapeutic development of HFpEF based on the complex relationships between aging, comorbidities, and HFpEF.

Background: The 15-item Geriatric Depression Scale (GDS-15) shows good performance in detecting depression among older persons, but its applicability has not been well studied in non-Western oldest-old adults and centenarians. This study aimed to evaluate the psychometric property of the GDS-15 and a simplified version among a large representative longevous population in China. Methods: A total of 1624 individuals (786 oldest-old persons aged from 80 to 99 years; 838 centenarians aged 100+ years) participated in this study. Home interviews with structured questionnaires were conducted to collect sociodemographic data. Depressive symptoms were measured using the Chinese GDS-15 version. We implemented mixed methods for the psychometric evaluation of the GDS-15. Cronbach’s α coefficient and item-total correlation coefficients were used to evaluate the internal consistency. A standard expert consultation was conducted to test the content validity of each item. Multiple factor analyses were used to explore the optimal factor structure and measurement invariance. Results: The α coefficient of the GDS-15 was 0.745, while two items impaired the overall consistency reliability. Nineteen experts rated the applicability for each item and provided removal suggestion. Five items with less validity were removed, and a simplified 10-item GDS model with three-factor structure was proposed as an optimal solution. The GDS-10 model showed factorial equivalence across age, sex, residence, and education in multi-group confirmatory factor analyses. Conclusions: The original GDS-15 has acceptable internal reliability, known-group validity, and concurrent validity among Chinese community-dwelling oldest-old and centenarians; however we provided preliminary evidence indicating that individual items related to somatic function or social activities may not be applicable for this population. The modified GDS-10 can be proposed as a potentially more practical and comprehensible instrument for depression screening.