Diet and lifestyle behaviours simultaneously act on frailty: it is time to move the threshold of frailty prevention and control forward.

BACKGROUND: To analyse the association among the simultaneous effects of dietary intake, daily life behavioural factors, and frailty outcomes in older Chinese women, we predicted the probability of maintaining physical robustness under a combination of different variables. METHODS: The Fried frailty criterion was used to determine the three groups of "frailty", "pre-frailty", and "robust", and a national epidemiological survey was performed. The three-classification decision tree model was fitted, and the comprehensive performance of the model was evaluated to predict the probability of occurrence of different outcomes. RESULTS: Among the 1,044 participants, 15.9% were frailty and 50.29% were pre-frailty; the overall prevalence first increased and then decreased with age, reaching a peak at 70-74 years of age. Through univariate analysis, filtering, and embedded screening, eight significant variables were identified: staple food, spices, exercise (frequency, intensity, and time), work frequency, self-feeling, and family emotions. In the three-classification decision tree, the values of each evaluation index of Model 3 were relatively average; the accuracy, recall, specificity, precision, and F1 score range were between 75% and 84%, and the AUC was also greater than 0.800, indicating excellent performance and the best interpretability of the results. Model 3 takes exercise time as the root node and contains 6 variables and 10 types, suggesting the impact of the comprehensive effect of these variables on robust and non-robust populations (the predicted probability range is 6.67-93.33%). CONCLUSION: The combined effect of these factors (no exercise or less than 0.5 h of exercise per day, occasional exercise, exercise at low intensity, feeling more tired at work, and eating too many staple foods (> 450 g per day) are more detrimental to maintaining robustness.

Renal lipid accumulation and aging linked to tubular cells injury via ANGPTL4.

Renal tubular epithelial cells are vulnerable to stress-induced damage, including excessive lipid accumulation and aging, with ANGPTL4 potentially playing a crucial bridging role between these factors. In this study, RNA-sequencing was used to identify a marked increase in ANGPTL4 expression in kidneys of diet-induced obese and aging mice. Overexpression and knockout of ANGPTL4 in renal tubular epithelial cells (HK-2) was used to investigate the underlying mechanism. Subsequently, ANGPTL4 expression in plasma and kidney tissues of normal young controls and elderly individuals was analyzed using ELISA and immunohistochemical techniques. RNA sequencing results showed that ANGPTL4 expression was significantly upregulated in the kidney tissue of diet-induced obesity and aging mice. In vitro experiments demonstrated that overexpression of ANGPTL4 in HK-2 cells led to increased lipid deposition and senescence. Conversely, the absence of ANGPTL4 appears to alleviate the impact of free fatty acids (FFA) on aging in HK-2 cells. Additionally, aging HK-2 cells exhibited elevated ANGPTL4 expression, and stress response markers associated with cell cycle arrest. Furthermore, our clinical evidence revealed dysregulation of ANGPTL4 expression in serum and kidney tissue samples obtained from elderly individuals compared to young subjects. Our study findings indicate a potential association between ANGPTL4 and age-related metabolic disorders, as well as injury to renal tubular epithelial cells. This suggests that targeting ANGPTL4 could be a viable strategy for the clinical treatment of renal aging.

Inflection Point Age in the Middle and Older Women - Jiangxi Province, China, 2020-2022.

What is already known about this topic?: Previous studies have predominantly examined the micro-level aspects of women aging inflection points, while macro-level research using big data on the inflection points of aging among middle-aged and elderly women in China is currently limited. What is added by this report?: This study determined the inflection ages for physiological, psychological, social, and total dimensions in middle-aged, young elderly, and elderly women [(48.0-53.2) vs. (66.3-70.0) vs. (78.4-81.2) years old]. What are the implications for public health practice?: This study is important for gaining a deeper understanding of aging, identifying patterns of aging, and implementing targeted interventions to promote the overall health of Chinese women.

NOP14 as a Potential Predictor of Adult-Type Diffuse Glioma Prognosis and Immunotherapy, is Related to Cell Migration, Proliferation, and CD8+T Cell Infiltration.

BACKGROUND: World Health Organization (WHO) grade 4 adult-type diffuse glioma is the most malignant primary tumor of the brain. Nucleolar protein 14 (NOP14) is recognized to contribute significantly to the assembly of small ribosomal subunits. However, the specific involvement of NOP14 in diverse cancers remains poorly understood, particularly its role in adult-type diffuse glioma, which has yet to be elucidated. METHODS: A total of 20 adult-type diffuse glioma samples with varying WHO stages were collected. The protein level of NOP14 was detected using immunohistochemistry. Additionally, NOP14 expression in LN229 and U251 cell lines and collected clinical tissue samples was quantified using the Western blot technique. Furthermore, the correlation between NOP14 and clinicopathological features, survival rates, matrix and immune scores, and immune components was investigated using data from the Cancer Gene Atlas database. RESULTS: NOP14 exhibited high expression in adult-type diffuse glioma patients, with the highest expression observed in the LN229 cell line. Moreover, elevated NOP14 expression was significantly correlated with poorer overall survival and demonstrated an association with unfavorable pathological features in a cohort of 703 glioblastoma (GBM) patients. Evidence of a connection between NOP14 and the tumor microenvironment was presented. Elevated NOP14 was linked to the infiltration of CD8+T cell and factors related to epithelial-mesenchymal transition. In in vitro assay, NOP14 was capable of suppressing adult-type diffuse glioma cell invasion and metastasis. CONCLUSIONS: NOP14 holds great promise as a candidate biomarker for detecting prognostic, molecular, and immune signatures of adult-type diffuse glioma.

Myricetin alleviates diabetic cardiomyopathy by regulating gut microbiota and their metabolites.

BACKGROUND: The gut microbiota is involved in the pathogenesis of diabetic cardiomyopathy (DCM). Myricetin protects cardiac function in DCM. However, the low bioavailability of myricetin fails to explain its pharmacological mechanisms thoroughly. Research has shown that myricetin has a positive effect on the gut microbiota. We hypothesize that myricetin improves the development of DCM via regulating gut microbiota. METHODS: DCM mice were induced with streptozotocin and fed a high-fat diet, and then treated with myricetin by gavage and high-fat diet for 16 weeks. Indexes related to gut microbiota composition, cardiac structure, cardiac function, intestinal barrier function, and inflammation were detected. Moreover, the gut contents were transplanted to DCM mice, and the effect of fecal microbiota transplantation (FMT) on DCM mice was assessed. RESULTS: Myricetin could improve cardiac function in DCM mice by decreasing cardiomyocyte hypertrophy and interstitial fibrosis. The composition of gut microbiota, especially for short-chain fatty acid-producing bacteria involving Roseburia, Faecalibaculum, and Bifidobacterium, was more abundant by myricetin treatment in DCM mice. Myricetin increased occludin expression and the number of goblet cells in DCM mice. Compared with DCM mice unfed with gut content, the cardiac function, number of goblet cells, and expression of occludin in DCM mice fed by gut contents were elevated, while cardiomyocyte hypertrophy and TLR4/MyD88 pathway-related proteins were decreased. CONCLUSIONS: Myricetin can prevent DCM development by increasing the abundance of beneficial gut microbiota and restoring the gut barrier function.

Repeated high­intensity focused ultrasound combined with iodine­125 seed interstitial brachytherapy offers improved quality of life and pain control for patients with advanced pancreatic cancer: A 52­patient retrospective study.

Patients diagnosed with pancreatic cancer who have 5-year survival rates of ~5% are typically in the advanced stage. Pancreatic cancer has become the third leading cause of cancer-related death in the United States and there is still a lack of effective treatments to improve patient survival rate. Hence, the purpose of the present retrospective study was to assess the potential clinical impact of repeated high-intensity focused ultrasound (HIFU) combined with iodine-125 (125I) interstitial brachytherapy for the treatment of patients with advanced pancreatic cancer who were ineligible for or declined surgery and chemotherapy. A total of 52 patients diagnosed with advanced pancreatic cancer were included in the study. At least one course of HIFU therapy combined with percutaneous ultrasound-guided 125I seed implantation was administered to each patient. The clinical assessment included an evaluation of Karnofsky Performance Scale (KPS) score at baseline, and at 1 and 2 months after combined therapy. Pain intensity was additionally evaluated with the numerical rating score (NRS). Overall survival (OS) times and survival rates at 3, 6, 9 and 12 months after combined treatment were evaluated. Adverse events commonly associated with HIFU and 125I seed implantation were recorded, and the severity of adverse events was graded according to the Common Terminology Criteria for Adverse Events, version 4. All 52 patients received successful repeated HIFU treatment combined with 125I seed implantation and were included in the analysis of efficacy and safety. The median OS time of patients was estimated to be 13.1 months (95% CI, 11.3-14.8). The survival rates at 3, 6, 9 and 12 months were 100.0, 86.5, 61.5 and 53.8%, respectively. The mean KPS score was 62.7±6.3 at baseline, 73.7±7.9 at 1 month and 68.8±6.5 at 2 months after combined treatment. KPS score increased significantly after combined therapy. The mean NRS score was 6.7±1.6 at baseline, and 4.7±1.7 and 5.4±1.5 at 1 and 2 months after combined treatment, respectively. The number of patients with severe pain and the NRS score were both significantly lower at 1 and 2 months after 125I seed implantation compared with those at baseline. No serious complications were detected during the follow-up period. In conclusion, the present study demonstrated the survival benefit and improvement in quality of life of patients with advanced pancreatic cancer receiving repeated HIFU treatment combined with 125I interstitial brachytherapy, which may provide new ideas and methods for the treatment of pancreatic cancer.

Age-Related Gut Microbiota Transplantation Disrupts Myocardial Energy Homeostasis and Induces Oxidative Damage.

BACKGROUND: Aging-related energy homeostasis significantly affects normal heart function and disease development. The relationship between the gut microbiota and host energy metabolism has been well established. However, the influence of an aged microbiota on energy metabolism in the heart remains unclear. OBJECTIVE: The objective of this was to explore the effects of age-related microbiota composition on energy metabolism in the heart. METHODS: In this study, we used the fecal microbiota transplantation (FMT) method. The fecal microbiota from young (2-3 mo) and aged (18-22 mo) donor mice were transplanted into separate groups of young (2-3 mo) recipient mice. The analysis utilized whole 16S rRNA sequencing and plasma metabolomics to assess changes in the gut microbiota composition and metabolic potential. Energy changes were monitored by performing an oral glucose tolerance test, biochemical testing, body composition analysis, and metabolic cage measurements. Metabolic markers and markers of DNA damage were assessed in heart samples. RESULTS: FMT of an aged microbiota changed the composition of the recipient's gut microbiota, leading to an elevated Firmicutes-to-Bacteroidetes ratio. It also affected overall energy metabolism, resulting in elevated plasma glucose concentrations, impaired glucose tolerance, and epididymal fat accumulation. Notably, FMT of an aged microbiota increased the heart weight and promoted cardiac hypertrophy. Furthermore, there were significant associations between heart weight and cardiac hypertrophy indicators, epididymal fat weight, and fasting glucose concentrations. Mechanistically, FMT of an aged microbiota modulated the glucose metabolic pathway and induced myocardial oxidative damage. CONCLUSIONS: Our findings suggested that an aged microbiota can modulate metabolism and induce cardiac injury. This highlights the possible role of the gut microbiota in age-related metabolic disorders and cardiac dysfunction.

Fecal transplantation of young mouse donors effectively improves enterotoxicity in elderly recipients exposed to triphenyltin.

Triphenyltin (TPT) is a widely used biocide known for its high toxicity to various organisms, including humans, and its potential contribution to environmental pollution. The aging process leads to progressive deterioration of physiological functions in the elderly, making them more susceptible to the toxic effects of environmental pollutants. This study aimed to investigate the mitigating effect of fecal transplantation in young mice on the toxicological impairment caused by TPT exposure. For the study, 18-month-old mice were divided into four groups with six replicates each. The control group was fed a basal diet, the TPT group was exposed to 3.75 mg/Kg TPT, the feces group received fecal transplantation from 8-week-old young mice, and the combined group was exposed to 3.75 mg/Kg TPT after receiving fecal transplantation. Compared with the elderly control group, TPT induced significant upregulation of mRNA expression of pro-inflammatory factors (IL-1ß, IL-6, TNF-α), while the anti-inflammatory factor gene IL-10 was significantly suppressed. The mRNA expression of intestinal barrier proteins (Claudin, Occludin, Muc2) was also significantly downregulated. However, fecal transplantation in young mice alleviated TPT-induced changes in inflammatory factors, ameliorated oxidative stress, and increased the activities of antioxidant enzymes (including SOD, CAT, GSH-Px). Further analysis using 16 s RNA showed that exposure to TPT led to changes in the composition of the intestinal flora. Untargeted metabolomics observations of feces from older mice revealed that exposure to TPT resulted in altered fecal metabolites. Fecal transplantation in young mice altered the microbiota of TPT-exposed older mice, especially by enhancing the levels of core probiotics. Similar beneficial effects were observed through untargeted metabolomics. Overall, this study highlights the potential benefits of young fecal transplantation in protecting the elderly from the toxicity of TPT, offering a promising approach to improve healthy aging.

Exposure to triphenyltin impairs gut integrity, disturbs gut microbiota, and alters fecal metabolites.

Triphenyltin is an environmental contaminant widely used in antifouling paints and can cause toxicity in various organs in living organisms. However, its effects on intestinal function and the microbiome of the gut remain unknown. The objective of this study was to explore the intestinal toxicity of triphenyltin in mice by orally administering 0, 1.875, 3.75, and 7.5 mg/Kg to adult male mice for 8 weeks. Results showed that triphenyltin caused ileum tissue damage, induced oxidative stress, upregulated inflammation-related gene expression and increased serum tumor-necrosis factor α (TNF-α) levels in mice. Triphenyltin impaired ileum barrier function by downregulating Muc2, ZO-1, Occludin and their protein levels at 3.75 and 7.5 mg/Kg. TPT exposure led to partial inflammation and decreased mucin mRNA expression in the colon. Triphenyltin altered intestinal micro-ecological balance and fecal metabolome in mice. In conclusion, triphenyltin alters the mouse gut microbiota and fecal metabolome.

Roles of Human Gut Microbiota in Liver Cirrhosis Risk: A Two-Sample Mendelian Randomization Study.

BACKGROUND: Accumulating evidence suggests that alterations in gut microbiota composition and diversity are associated with liver cirrhosis. But whether gut microbiota promotes or hampers the genesis and development of liver cirrhosis remains vague. OBJECTIVES: This study aimed to establish a causal relationship between gut microbiota and the development of liver fibrosis and cirrhosis. To achieve this, we employed a 2-sample Mendelian randomization (MR) analysis utilizing genome-wide association study (GWAS) summary statistics. This approach enabled us to assess the potential impact of gut microbiota on liver cirrhosis. METHODS: The independent genetic instruments of gut microbiota were obtained from the MiBioGen (up to 18,340 participants), which is a large-scale genome-wide genotype and 16S fecal microbiome dataset. Cirrhosis data were derived from the FinnGen biobank analysis, which included 214,403 individuals of European ancestry (811 patients and 213,592 controls). To assess the causal relationship between gut microbiota and cirrhosis, we applied 4 different methods of MR analysis: the inverse-variance weighted method (IVW), the MR-Egger regression, the weighted median analysis (WME), and the weighted mode. Furthermore, sensitivity analyses were conducted to evaluate heterogeneity and horizontal pleiotropy. RESULTS: Results of MR analyses provided evidence of a causal association between 4 microbiota features and cirrhosis, including 2 family [Lachnosiraceae: odds ratio (OR): 1.82626178; 95% confidence interval (CI): 1.05208209, 3.17012532; P = 0.0323194; Lactobacillaceae : OR: 0.62897502; 95% CI: 0.42513162, 0.93055788; P = 0.02033345] and 2 genus [Butyricicoccus: OR: 0.41432215; 95% CI: 0.22716865, 0.75566257; P = 0.0040564; Lactobacillus: OR: 0.6663767; 95% CI: 0.45679511, 0.97211616; P = 0.03513627]. CONCLUSIONS: Our findings offered compelling evidence of a causal association between gut microbiota and cirrhosis in European population and identified specific bacteria taxa that may regulate the genesis and progression of liver fibrosis and cirrhosis, may offer a new direction for the treatment of cirrhosis.

Correlation of serum VEGF-C, ANGPTL4, and activin A levels with frailty.

BACKGROUND: Secretory factors linked to lymphogenesis, such as vascular endothelial growth factor C (VEGF-C), angiopoietin like protein 4 (ANGPTL4), and activin A (ACV-A), have been recognized as potential markers of chronic inflammatory status and age-related diseases. Furthermore, these factors may also be linked to frailty. The primary objective of this study was to examine the serum VEGF-C, ANGPTL4, and ACV-A levels in young individuals, healthy older individuals, and older individuals with pre-frailty and frailty, and to determine their association with pro-inflammatory factor levels. METHODS: We conducted an observational study, enrolling a total of 210 older individuals and 20 young healthy volunteers. Participants were divided into four groups based on the Freid frailty phenotype: healthy young group, older patients without frailty group, pre-frail older group, and frail older group. Plasma and peripheral blood mononuclear cells (PBMCs) were collected from all four groups. ELISA was used to measure the serum levels of VEGF-C, ANGPTL4, ACV-A, and pro-inflammatory cytokines, while RT-qPCR was used to measure the transcription level of VEGF-C, ANGPTL4 and ACV-A in PBMCs. RESULTS: In comparison to healthy young individuals and older participants without frailty, older participants with frailty exhibited lower renal function, higher serum levels and transcription levels of VEGF-C, ANGPTL4, ACV-A, and elevated levels of pro-inflammatory cytokines (CRP, IL-1ß, and TNF-α). Multiple linear regression analysis revealed that serum levels of VEGF-C, ANGPTL4, and ACV-A were positively correlated with the frailty index, independent of age, eGFR, and comorbidities. Furthermore, the receiver operating characteristic (ROC) curve analysis demonstrated that serum levels of VEGF-C, ANGPTL4, and ACV-A have great accuracy in predicting frailty. CONCLUSION: Elevated serum levels of VEGF-C, ANGPTL4, and ACV-A are associated with frailty status.

High blood galectin-3 level associated with risk of frailty in aging.

Background: Frailty is one of the most problematic expressions of population aging, but its underlying mechanism has not been fully elucidated. Circulating galectin-3 (Gal-3) is involved in the pathogenesis of many age-related diseases. This study aims to explore the influence of circulating Gal-3 on the regulation of frailty and aging and to identify the potential mechanism further. Methods: In this cross-sectional analysis, the Fried frailty phenotype (FP) was assessed among 149 community elderly residents in Shanghai. Peripheral blood mononuclear cells (PBMCs) were isolated by the Ficoll-Paque density gradient method, and differentially expressed genes (DEGs) encoding transcription factors in frailty were detected by Illumina and bioinformatics analyzed with R software. Gene Ontology (GO) enrichment analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to explore the functional roles of these DEGs and the target genes related to frailty phenotypes. The serum Gal-3 concentration was tested by enzyme-linked immunosorbent assay (ELISA). Mouse frailty phenotype was used to construct an in vivo model of frailty, after which the serum levels of circulating Gal-3 and its gene expression levels in mouse tissues were determined. Results: Participants' mean age was 72.04 ± 7.05 years. In total, 21.48% were frail and 36.91% were pre-frail. The mean serum Gal-3 concentration was 46.34 ± 17.99 ng/mL in frail participants, 32.30 ± 8.14 ng/mL in pre-frail participants, and 26.00 ± 5.87 ng/mL in non-frail individuals (p < 0.001). Significant positive correlations between serum Gal-3 level and FP score, SARC-F score, C-reactive protein (CRP), interleukin-6, etc., were observed. In addition, the KEGG pathway and GO enrichment analyses showed that 265 DEGs in PBMCs of frail participants were mainly related to inflammatory response, translation, RNA binding, protein binding, ribosome, and primary immunodeficiency. LGALS3 was identified as the overlapping gene between frailty-related DEGs and aging-related DEGs. The elevated serum Gal-3 concentration in the in vivo model of frailty was consistent with the results in participants. Conclusion: In both community-dwelling older adults and aged mice, serum Gal-3 concentration was positively correlated with frailty. This circulating mediator may be a promising indicator of frailty. Clinical trial registration: Chinese Clinical Trial Registry identifier, ChiCTR2000036399.

How long were older people expected to live with or without sarcopenia? Multistate modeling of a national cohort study.

Objectives: Sarcopenia is well known to be associated with mortality, but there is a lack of evidence on the estimates of life expectancy (LE) for sarcopenia in China. This study aims to estimate total life expectancy (TLE) and sarcopenia-specific LE in community-dwelling older Chinese adults with and without sarcopenia. Methods: This study included participants aged 60 years and older who enrolled in the cohort in 2011 and 2013 and at least completed one follow-up until 2015 as part of the China Health and Retirement Longitudinal Study (CHARLS). The criteria for defining sarcopenia were based on the guidelines established by the Asian Working Group on Sarcopenia in 2019. TLE and sarcopenia-specific LE were estimated for the total population and subgroups using continuous-time multistate modeling. Results: A total of 6,029 participants (49.2% women) with an average age of 68.4 (SD: 6.56) years were included in the study. The baseline prevalence of sarcopenia and possible sarcopenia was 19.5 and 44.9%, respectively. We observed that sarcopenia stages naturally deteriorated to worse stages (including death, by 24.4%) and returned to better stages (17.1%) during a median follow-up of 3.92 years (IQR: 2.00 ~ 4.00). The average TLE at the age of 60 was 20.9 [95% CI: 20.2-21.5] years (22.1 [95% CI: 19.6-24.6] for non-sarcopenic older adults, 20.9 [95% CI: 19.5-22.3] for possible sarcopenic, and 18.7 [95% CI: 16.4-21.1] for sarcopenic). Men, former and current smokers, and those living in northwest China had less TLE. Sarcopenic older adults, those with lower education, those who are unmarried, those with agriculture hukou, and those living in rural and northwest China were expected to live fewer years with non-sarcopenia. Sarcopenic older people, men, those with agriculture hukou, and those living in rural and southwest China were expected to live more years with sarcopenia. Discussion: The results improved our understanding of the relationship between sarcopenia and life expectancy. We suggested that targeted strategies should be considered in high-risk populations and underdeveloped regions to prevent sarcopenia and improve non-sarcopenic life years for the older population.

A rapid and high-throughput multiplex genetic detection assay for detection, semi-quantification and virulence genotyping of Helicobacter pylori in non-invasive oral samples.

Aim: This study established a high-throughput multiplex genetic detection assay (HMGA) for rapid identification, semi-quantification and virulence analysis of Helicobacter pylori directly from the clinical non-invasive oral samples. Methods: The gastric mucosa and oral samples were collected from 242 patients in Shanghai from 2021 to 2022. All the samples were detected by routine clinical tests for H. pylori and Sanger sequenced for inconsistent results. A new multiplex PCR assay providing results within 4 hours was designed and optimized involving fluorescent dye-labeled specific primers targeted 16S rRNA gene, semi-quantitative gene ureC and 10 virulence genes of H. pylori. Semi-quantification was carried out by simulating the serial 10-fold dilutions of positive oral samples, and the H. pylori loads in different clinical samples were further compared. The mixed plasmids of virulence genes vacA s1, vacA m1 and vacA m2 were used to evaluate the performance on different genotypes. The consistency of 10 virulence genes in gastric mucosa, saliva, mouthwash and dental plaque of H. pylori-positive patients was compared. Results: The non-invasive HMGA was highly specific for detection of all 12 targets of H. pylori and human internal reference gene ß-globin, and the sensitivity to all target genes could reach 10 copies/µL. Compared with routine clinical tests and sequencing, non-invasive HMGA has a high level (>0.98) of sensitivity, specificity, accuracy, PPV, NPV and kappa coefficient for direct detection of H. pylori in oral samples. Moreover, by detecting peak area levels of ureC, it was confirmed that the H. pylori loads in gastric mucosa were significantly higher than those of the three kinds of oral samples (p<0.05). We also found that 45.0% (91/202) of patients had different H. pylori virulence genes in different oral samples. The concordance of positive detection rates of each virulence gene between saliva and gastric mucosa was more than 78% (p<0.05). Conclusion: The non-invasive HMGA proved to be a reliable method for the rapid H. pylori identification, semi-quantification and detection of 10 virulence genes directly in oral samples, providing a new idea for non-invasive detection of H. pylori.

The overall and domain-specific quality of life of Chinese community-dwelling older adults: the role of intrinsic capacity and disease burden.

Objective: This study aimed to investigate the impact of the different domains of intrinsic capacity (IC) and chronic disease burden on health-related quality of life (HRQoL) and domain-specific HRQoL in Chinese community-dwelling older adults. Design: A cross-sectional observational study of a community-based cohort. Participants: We evaluated Chinese older adults (n = 429, mean age, 72.91 ± 7.014 years; female proportion, 57.30%). Measurements: IC contains five domains, namely locomotion, vitality, cognition, psychological, and sensory capacity. Locomotion dysfunction was defined as grip and/or gait decline. Vitality decline was defined if two of the following three parameters were present: fatigue, physical inactivity, and weight loss or overweight. Cognition was classified into normal cognition, pre-mild cognitive impairment (pre-MCI), and MCI according to the normative z-scores of the neuropsychological test battery. Psychological dysfunction was diagnosed based on depressive symptoms. Sensory dysfunction was defined as hearing and/or vision impairment. HRQoL was assessed using the AQoL-8D scale, which comprised physical (including independent living, senses, and pain) and psychosocial (including mental health, happiness, self-worth, coping, and relationships) dimensions. Low HRQoL (HRQoL score or subscores in the highest quintile) was used as a dependent variable in logistic regression analyses adjusted for demographic, health-related, and psychological confounders. Results: Sensory impairment was an independent determinant of senses, and locomotion impairment was significantly associated with overall HRQoL, independent living, and pain in the physical dimension of HRQoL. Cognition was an independent determinant of the senses. Vitality was independently associated with overall HRQoL, senses, and pain in the physical dimension and mental health and relationships in the psychological dimension of HRQoL. The psychological domain of IC was independently associated with overall and domain-specific HRQoL apart from senses after adjustment for all confounders. The number of multimorbidities mainly had a significant impact on independent living after adjustment for all confounders. Conclusion: IC domains and chronic disease burden had heterogeneous influences on overall and domain-specific HRQoL. The impairment of sensory and locomotion domains had a synergistic impact on the overall and physical dimensions of HRQoL. The vitality and psychological domains of IC had more profound effects on HRQoL. Older people with high morbidity might have a higher risk of poor independent living.

Mast cell activation may contribute to adverse health transitions in COVID-19 patients with frailty.

A prominent aspect of the post-coronavirus disease-2019 (post-COVID-19) era is long-COVID. Therefore, precise patient classification and exploration of the corresponding factors affecting long-COVID are crucial for tailored treatment strategies. Frailty is a common age-related clinical syndrome characterized by deteriorated physiological functions of multiple organ systems, which increases susceptibility to stressors. Herein, we performed an inclusion and exclusion analysis (definite COVID-19 infection diagnosis, clear underlying disease information, ≥60 years old, and repeated sampling of clinical cases) of 10,613 blood samples and identified frailty cases for further investigation. RNA-Seq data were used for differential gene expression and functional and pathway analyses. The results revealed that patients with frailty were more prone to poor health conversions and more sequelae, and the blood transcriptome had obvious disturbances in pathways associated with immune regulation, metabolism, and stress response. These adverse health transitions were significantly associated with mast cell activation. Additionally, NCAPG, MCM10, and CDC25C were identified as hub genes in the peripheral blood differential gene cluster, which could be used as diagnostic markers of poor health conversion. Our results indicate that healthcare measures should be prioritized to mitigate adverse health outcomes in this vulnerable patient group, COVID-19 patients with frailty, in post-COVID era.

Effects of 30% vs. 60% inspired oxygen fraction during mechanical ventilation on postoperative atelectasis: a randomised controlled trial.

BACKGROUND: There is the ongoing debate over the effect of inspired oxygen fraction (FiO2) during mechanical ventilation on postoperative atelectasis. We aimed to compare the effects of low (30%) and moderate (60%) FiO2 on postoperative atelectasis. The hypothesis of the study was that 30% FiO2 during mechanical ventilation could reduce postoperative atelectasis volume compared with 60% FiO2. METHODS: We performed a randomized controlled trial with 120 patients. Subjects were randomly assigned to receive 30% or 60% FiO2 during mechanical ventilation in a 1:1 ratio. The primary outcome was the percentage of postoperative atelectasis volume in the total lung measured using chest CT within 30 min after extubation. The secondary outcomes included different aeration region volumes, incidence of clinically significant atelectasis, and oxygenation index. RESULTS: In total, 113 subjects completed the trial, including 55 and 58 subjects in the 30% and 60% FiO2 groups, respectively. The percentage of the postoperative atelectasis volume in the 30% FiO2 group did not differ from that in the 60% FiO2 group. Furthermore, there was no significant difference in the atelectasis volume between the two groups after the missing data were imputed by multiple imputation. Additionally, there were no significant differences in the volumes of the over-aeration, normal-aeration, and poor-aeration regions between the groups. No significant differences in the incidence of clinically significant atelectasis or oxygenation index at the end of surgery were observed between the groups. CONCLUSIONS: Compared with 60% FiO2, the use of 30% FiO2 during mechanical ventilation does not reduce the postoperative atelectasis volume. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ). Identifier: ChiCTR1900021635. Date: 2 March 2019. Principal invetigator: Weidong Gu.

A potential correlation between adipokines, skeletal muscle function and bone mineral density in middle-aged and elderly individuals.

BACKGROUND: Evidence exists of a strong association between inflammation and a decrease in skeletal muscle function and bone mineral density (BMD); however, the specific mechanisms of these associations remain unclear. Adipokines, as key regulators of the inflammatory response, may be implicated in these processes. The objective of this study was to explore the potential correlation between adipokines, skeletal muscle function and BMD in middle-aged and elderly individuals. METHODS: A comparative cross-sectional study was carried out at the Huadong Hospital Affiliated with Fudan University (Shanghai, China). A total of 460 middle-aged and elderly individuals were recruited, and 125 were enrolled in the analysis. Their biochemical indices, body composition, skeletal muscle function and BMD were measured. Bioinformatic analysis was also employed to identify potential adipokine targets linked to skeletal muscle function and BMD. To validate these targets, plasma and peripheral blood mononuclear cells (PBMCs) were harvested from these individuals and subjected to western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). RESULTS: Individuals in this cross-sectional study were categorized into 2 groups according to their median skeletal muscle mass (SMM) (28.8 kg for males and 20.6 kg for females). Individuals with lower SMM exhibited poorer grip strength (P = 0.017), longer 5-Times-Sit-to-Stand Test (FTSST) duration (P = 0.029), lower total hip BMD (P = 0.043), lower femoral neck BMD (P = 0.011) and higher levels of inflammatory markers in comparison with individuals with higher SMM. Bioinformatics analysis identified LEP, ADIPOQ, RBP4, and DPP4 as potential adipokine targets associated with skeletal muscle function and BMD. In vitro experiments demonstrated that individuals with decreased skeletal muscle function and BMD expressed higher levels of these adipokines. CONCLUSIONS: Skeletal muscle function is positively correlated with BMD and negatively correlated with levels of inflammatory markers among middle-aged and elderly individuals. Those with lower skeletal muscle function and BMD tend to have a higher expression of LEP, ADIPOQ, RBP4 and DPP4.

Urinary microRNAs in sepsis function as a novel prognostic marker.

Renal dysfunction is a common complication of sepsis. Early diagnosis and prompt treatment of sepsis with renal insufficiency are crucial for improving patient outcomes. Diagnostic markers can help identify patients at risk for sepsis and AKI, allowing for early intervention and potentially preventing the development of severe complications. The aim of the present study was to investigate the expression difference of urinary microRNAs (miRNAs/miRs) in elderly patients with sepsis and secondary renal insufficiency, and to evaluate their diagnostic value in these patients. In the present study, RNA was extracted from urine samples of elderly sepsis-related acute renal damage patients and the expression profiles of several miRNAs were analyzed. In order to evaluate the expression profile of several miRNAs, urine samples from elderly patients with acute renal damage brought on by sepsis were obtained. RNA extraction and sequencing were then performed on the samples. Furthermore, multiple bioinformatics methods were used to analyze miRNA profiles, including differential expression analysis, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of different miRNA target genes, to further explore miRNAs that are suitable for utilization as biomarkers. A total of four miRNAs, including hsa-miR-31-5p, hsa-miR-151a-3p, hsa-miR-142-5p and hsa-miR-16-5p, were identified as potential biological markers and were further confirmed in sepsis using reverse transcription-quantitative PCR. The results of the present study demonstrated that the four urinary miRNAs were differentially expressed and may serve as specific markers for prediction of secondary acute kidney injury in elderly patients with sepsis.

ACE2 negatively regulates the Warburg effect and suppresses hepatocellular carcinoma progression via reducing ROS-HIF1α activity.

Aerobic glycolysis has pleiotropic roles in the pathogenesis of hepatocellular carcinoma (HCC). Emerging studies revealed key promoters of aerobic glycolysis, however, little is known about its negative regulators in HCC. In this study, an integrative analysis identifies a repertoire of differentially expressed genes (DNASE1L3, SLC22A1, ACE2, CES3, CCL14, GYS2, ADH4, and CFHR3) that are inversely associated with the glycolytic phenotype in HCC. ACE2, a member of the rennin-angiotensin system, is revealed to be downregulated in HCC and predicts a poor prognosis. ACE2 overexpression significantly inhibits the glycolytic flux as evidenced by reduced glucose uptake, lactate release, extracellular acidification rate, and the expression of glycolytic genes. Opposite results are noticed in loss-of-function studies. Mechanistically, ACE2 metabolizes Ang II to Ang-(1-7), which activates Mas receptor and leads to the phosphorylation of Src homology 2-containing inositol phosphatase 2 (SHP-2). SHP2 activation further blocks reactive oxygen species (ROS)-HIF1α signaling. Addition of Ang-(1-7) or the antioxidant N-acetylcysteine compromises in vivo additive tumor growth and aerobic glycolysis induced by ACE2 knockdown. Moreover, growth advantages afforded by ACE2 knockdown are largely glycolysis-dependent. In clinical settings, a close link between ACE2 expression and HIF1α or the phosphorated level of SHP2 is found. Overexpression of ACE2 significantly retards tumor growth in patient-derived xenograft model. Collectively, our findings suggest that ACE2 is a negative glycolytic regulator, and targeting the ACE2/Ang-(1-7)/Mas receptor/ROS/HIF1α axis may be a promising therapeutic strategy for HCC treatment.