Associations of parity and cognitive decline, depression, and chronic comorbidity in West China: Results from WCHAT study.

OBJECTIVE: To investigate the associations between parity (the number of offspring a female has borne) and cognitive function, depression, and chronic comorbidity in Western China. METHODS: A total of 846 women aged 50-55 years were included in the current analysis. Cognitive status was measured using a 10-item short portable mental status questionnaire (SPMSQ). Depressive symptoms were assessed using the 15-item geriatric depression scale (GDS-15). Other characteristics were self-reported. The associations between parity and cognitive decline, depression, and chronic comorbidity were analyzed using univariable and multivariable models. Multivariable models were adjusted for age, ethnic group, occupation, marital status, educational level, lifestyle factors, and sleeping time. RESULTS: Among the enrolled women, 26.71% were either childless or had one child, 47.40% had two children, 18.32% had three children, and 7.57% had ≥4 children. Compared to women with low parity, women with two or more children exhibited a higher risk of cognitive decline. Moreover, having four or more children was significantly associated with depression and chronic comorbidity. After adjusting covariates, women with three or more children exhibited a higher risk of cognitive decline than those with low parity. However, high parity was not significantly associated with depression or chronic comorbidity after adjustment for covariates. CONCLUSION: Our study showed that ≥3 children was associated with cognitive decline in women. Longitudinal studies are needed to evaluate this conclusion and to investigate the mechanisms involved. More importantly, families and societies should pay more attention to women's long-term health outcomes related to fertility.

The diagnostic agreement of sarcopenic obesity with different definitions in Chinese community-dwelling middle-aged and older adults.

Background: In 2022, the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) launched a consensus on the diagnostic methods for sarcopenic obesity (SO). The study aimed to identify the prevalence and diagnostic agreement of SO using different diagnostic methods in a cohort of subjects from West China aged at least 50 years old. Methods: A large multi-ethnic sample of 4,155 participants from the West China Health and Aging Trend (WCHAT) study was analyzed. SO was defined according to the newly published consensus of the ESPEN/EASO. Furthermore, SO was diagnosed as a combination of sarcopenia and obesity. The criteria established by the Asian Working Group for Sarcopenia 2019 (AWGS2019) were used to define sarcopenia. Obesity was defined by four widely used indicators: percent of body fat (PBF), visceral fat area (VFA), waist circumference (WC), and body mass index (BMI). Cohen's kappa was used to analyze the diagnostic agreement of the above five diagnostic methods. Results: A total of 4,155 participants were part of the study, including 1,499 men (63.76 ± 8.23 years) and 2,656 women (61.61 ± 8.20 years). The prevalence of SO was 0.63-7.22% with different diagnostic methods. The diagnosis agreement of five diagnostic methods was poor-to-good (κ: 0.06-0.67). The consensus by the ESPEN/EASO had the poorest agreement with other methods (κ: 0.06-0.32). AWGS+VFA had the best agreement with AWGS+WC (κ = 0.67), and consensus by the ESPEN/EASO had the best agreement with AWGS+ PBF (κ = 0.32). Conclusion: The prevalence and diagnostic agreement of SO varies considerably between different diagnostic methods. AWGS+WC has the highest diagnostic rate in the diagnosis of SO, whereas AWGS+BMI has the lowest. AWGS+VFA has a relatively good diagnostic agreement with other diagnostic methods, while the consensus of the ESPEN/EASO has a poor diagnostic agreement. AWGS+PBF may be suitable for the alternative diagnosis of the 2022 ESPEN/EASO.

The associations of daytime napping and motoric cognitive risk syndrome: Findings from the China Health and Retirement Longitudinal Study.

INTRODUCTION: Motoric cognitive risk syndrome (MCR), characterized by subjective cognitive complaints and slow gait in older populations, is associated with sleep duration. However, the association between MCR and daytime nap duration has not been thoroughly explored. METHODS: Baseline data from the China Health and Retirement Longitudinal Study (CHARLS) were used in this study. MCR was defined as the coexistence of subjective cognitive complaints and objective slow gait speed without a history of dementia or mobility disability. Daytime nap duration was categorized into four groups: no napping, short napping (<30 min), moderate napping (30-89 min) and extended napping (≥90 min). Multivariable logistic regression models were used to explore the association of daytime napping duration and MCR. RESULTS: A total of 4230 individuals aged ≥60 were included in the current analysis, of which 463 were diagnosed with MCR. Moderate napping of 30-89 min per day was found to be significantly associated with lower odds of MCR compared with the reference group of no napping. In subgroup analysis, individuals with sleep durations of <7 h per night had lower odds of MCR in the model that adjusted for all potential confounders with ≥30 min daytime nap duration compared with no napping. Interestingly, for people with a night sleep duration of 7-8 h, only those with a moderate nap of 30-89 min had lower odds of MCR than non-nappers after adjustment for potential confounders. CONCLUSION: A moderate nap of 30-89 min could lower the odds of MCR, especially for older adults with a night sleep duration of ≤8 h.

Nutrition Status Plays a Partial Mediation Role in the Relationship between Number of Teeth and Frailty: A Cross-Sectional Multicenter Study.

INTRODUCTION: Although the relationship between the number of teeth and frailty has been extensively studied, the mediating role of nutrition status in the association between the number of teeth and frailty remains to be clarified. METHODS: A number of 6,664 participants lived in the communities of West China were analyzed in our study. Physical frailty was determined based on the phenotype established by Fried. Nutrition status was evaluated using the Mini Nutrition Assessment-Short Form (MNA-SF) scale. Multiple linear regression was employed to evaluate the direct relationships between the number of teeth, nutrition, and frailty. Mediation models and structural equation model (SEM) pathway analysis were used to test the mediating role of nutrition status in the relationship between the number of teeth and frailty. RESULTS: Among the 6,664 participants aged over 50 years old, the prevalence of frailty was 6.2%. Multiple linear regression analysis showed a significant total relationship between the number of teeth (ß = -0.359, 95% CI: -0.473 to -0.244, p < 0.001) and frailty. After adjusting for MNA-SF scores, the relationship between the number of teeth and frailty remained significant (ß = -0.327, 95% CI: -0.443 to -0.211, p < 0.001), indicating a partial mediating effect of nutrition. Mediation analysis verified that nutrition partially mediated the relationship between the number of teeth and frailty (indirect effect estimate = -0.0121, bootstrap 95% CI: -0.0151 to -0.0092; direct effect estimate = -0.0874, bootstrap 95% CI: -0.1086 to -0.0678) in the fully adjusted model. This mediating effect occurred through influencing weight loss, low level of physical activity, and debility. SEM framework pathway analysis confirmed the association between the number of teeth, nutrition, and frailty. CONCLUSIONS: Our findings demonstrated that frailty was correlated with the number of teeth and poorer nutritional status, with nutrition partially mediating the correlation between the number of teeth and frailty. Our results supported early nutritional evaluation and intervention in oral health to decrease the risk of frailty.

Prevotella copri alleviates sarcopenia via attenuating muscle mass loss and function decline.

BACKGROUND: The gut microbiome and fecal metabolites have been found to influence sarcopenia, but whether there are potential bacteria that can alleviate sarcopenia has been under-investigated, and the molecular mechanism remains unclear. METHODS: To investigate the relationships between the gut microbiome, fecal metabolites and sarcopenia, subjects were selected from observational multi-ethnic study conducted in Western China. Sarcopenia was diagnosed according to the criteria of the Asian Working Group for Sarcopenia 2014. The gut microbiome was profiled by shotgun metagenomic sequencing. Untargeted metabolomic analysis was performed to analyse the differences in fecal metabolites. We investigated bacterium with the greatest relative abundance difference between healthy individuals and sarcopenia patients, and the differences in metabolites associated with the bacteria, to verify its effects on muscle mass and function in a mouse model. RESULTS: The study included 283 participants (68.90% females, mean age: 66.66 years old) with and without sarcopenia (141 and 142 participants, respectively) and from the Han (98 participants), Zang (88 participants) and Qiang (97 participants) ethnic groups. This showed an overall reduction (15.03% vs. 20.77%, P = 0.01) of Prevotella copri between the sarcopenia and non-sarcopenia subjects across the three ethnic groups. Functional characterization of the differential bacteria showed enrichment (odds ratio = 15.97, P = 0.0068) in branched chain amino acid (BCAA) metabolism in non-sarcopenia group. A total of 13 BCAA and their derivatives have relatively low levels in sarcopenia. In the in vivo experiment, we found that the blood BCAA level was higher in the mice gavaged with live P. copri (LPC) (P < 0.001). The LPC mice had significantly longer wire and grid hanging time (P < 0.02), longer time on rotor (P = 0.0001) and larger grip strength (P < 0.0001), indicating better muscle function. The weight of gastrocnemius mass and rectus femoris mass (P < 0.05) was higher in LPC mice. The micro-computed tomography showed a larger leg area (P = 0.0031), and a small animal analyser showed a higher lean mass ratio in LPC mice (P = 0.0157), indicating higher muscle mass. CONCLUSIONS: The results indicated that there were lower levels of both P. copri and BCAA in sarcopenia individuals. In vivo experiments, gavage with LPC could attenuate muscle mass and function decline, indicating alleviating sarcopenia. This suggested that P. copri may play a therapeutic potential role in the management of sarcopenia.

The hepatoprotective effect of aspirin on carbon tetrachloride­induced hepatic fibrosis via inhibition of TGFß­1 pathway and pro­inflammatory cytokines IL­1ß and COX­2 in rats.

Aspirin decreases liver fibrosis index and inflammation levels. However, the exact mechanism underlying the effects of aspirin are yet to be elucidated. The aim of the study was to investigate the potential protective effects of aspirin on carbon tetrachloride (CCl4)-induced hepatic fibrosis in Sprague-Dawley rats. Rats were divided into four groups, including healthy and CCl4 control and low-(aspirin 10 mg/kg + CCl4) and high-dose aspirin group (aspirin 300 mg/kg + CCl4). After 8 weeks treatment, the histopathological examinations of hepatocyte fibrosis in liver and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), IL-1ß, transforming growth factor-ß1 (TGF-ß1), hyaluronic acid (HA), laminin (LN) and type IV collagen (IV.C) were determined. Histopathological examination suggested that aspirin decreased CCl4-induced hepatic fibrosis and liver inflammation. The high-dose aspirin group significantly decreased the serum levels of ALT, AST, HA and LN compared with the CCl4 control group. High-dose aspirin group significantly decreased the levels of pro-inflammatory cytokines IL-1ß compared with CCl4 group. The high-dose aspirin group significantly inhibited the expression of TGFß-1 protein compared with CCl4 group. Overall, the present study indicated that aspirin exhibited potent protective effects against CCl4-induced hepatic fibrosis via inhibition of the TGFß-1 pathway and pro-inflammatory cytokine IL-1ß.

Individual and combined associations of body mass index and waist circumference with components of metabolic syndrome among multiethnic middle-aged and older adults: A cross-sectional study.

Objectives: Body mass index (BMI) and waist circumference (WC) are closely associated with metabolic syndrome and its components. Hence, a combination of these two obesity markers may be more predictive. In this study, we aimed to investigate the individual and combined associations of BMI and WC with selected components of metabolic syndrome and explored whether age, sex and ethnicity affected the aforementioned associations. Methods: A total of 6,298 middle-aged and older adults were included. Based on BMI and WC, the participants were divided into 4 groups: comorbid obesity (BMI ≥ 28 kg/m2 and WC< 85/90 cm for women/men), abdominal obesity alone (BMI< 28 kg/m2 and WC≥ 85/90 cm for women/men), general obesity alone (BMI ≥ 28 kg/m2 and WC< 85/90 cm for women/men) and nonobesity subgroups (BMI< 28 kg/m2 and WC< 85/90 cm for women/men). Selected components of metabolic syndrome were evaluated using the criteria recommended by the Chinese Diabetes Society. Poisson regression models with robust variance were used to evaluate the associations of obesity groups with selected components of metabolic syndrome. An interaction test was conducted to explore whether age, sex and ethnicity affect the aforementioned associations. Results: Compared with participants in the reference group (comorbid obesity), participants in the other 3 groups showed a decreased prevalence of fasting hyperglycemia (PR=0.83, 95% CI=0.73-0.94 for abdominal obesity alone, PR=0.60, 95% CI=0.38-0.96 for general obesity alone and PR=0.46, 95% CI=0.40-0.53 for nonobesity), hypertension (PR=0.86, 95% CI=0.82-0.90 for abdominal obesity alone, PR=0.80, 95% CI=0.65-0.97 for general obesity alone and PR=0.69, 95% CI = 0.66-0.73 for nonobesity) and hypertriglyceridemia (PR=0.88, 95% CI=0.82-0.95 for abdominal obesity alone, PR=0.62, 95% CI=0.47-0.81 for general obesity alone and PR=0.53, 95% CI=0.49-0.57 for nonobesity). However, participants in the abdominal obesity alone and nonobesity groups showed a decreased prevalence of low HDL-C levels while participants in the general obesity alone group did not (PR=0.65, 95% CI=0.41-1.03, p>0.05). In addition, the aforementioned associations were not affected by age, sex or ethnicity (all p for interactions>0.05). Conclusions: Comorbid obesity is superior to general and abdominal obesity in identifying individuals at high risk of developing metabolic syndrome in middle-aged and older adults. Great importance should be attached to the combined effect of BMI and WC on the prevention and management of metabolic syndrome.

Human brucellosis and fever of unknown origin.

BACKGROUND: Human brucellosis has become one of the major public health problems in China, and increases atypical manifestations, such as fever of unknown origin (FUO), and misdiagnosis rates has complicated the diagnosis of brucellosis. To date, no relevant study on the relationship between brucellosis and FUO has been conducted. METHODS: We retrospectively reviewed the medical charts of 35 patients with confirmed human brucellosis and prospectively recorded their outcomes by telephone interview. The patients were admitted to the Second Affiliated Hospital of Nanchang University between January 01, 2013 and October 31, 2019. Patient data were collected from hospital medical records. RESULTS: The percentage of males was significantly higher than that of female in FUO (78.95% vs. 21.05%, P < 0.05), and 80% of the patients had a clear history of exposure to cattle and sheep. Moreover, 19 (54%) cases were hospitalized with FUO, among which the patients with epidemiological histories were significantly more than those without (P < 0.05). The incidence of toxic hepatitis in FUO patients was higher than that in non-FUO patients (89% vs. 50%, P < 0.05). Meanwhile, the misdiagnosis rate was considerably higher in the FUO group than in the non-FUO group (100% vs. 63%; P < 0.05). CONCLUSION: Brucellosis is predominantly FUO admission in a non-endemic area of China, accompanied by irregular fever and toxic hepatitis. Careful examination of the epidemiological history and timely improvement of blood and bone marrow cultures can facilitate early diagnosis and prevent misdiagnosis.

Nutrition mediates the relationship between number of teeth and sarcopenia: a pathway analysis.

OBJECTIVES: The relationship between the number of teeth and sarcopenia remains poorly investigated. Although nutrition plays an important role in maintaining bone and muscle health, the complex relationship between number of teeth and nutrition in the pathogenesis of sarcopenia remains to be elucidated. METHODS: A large multi-ethnic sample of 4149 participants aged over 50 years old from West China Health and Aging Trend (WCHAT) study was analyzed. We examined the associations between number of teeth with nutritional status and sarcopenia, and the mediating role of nutrition in the association between number of teeth and sarcopenia. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019. We assessed nutrition using Mini Nutrition Assessment-Short Form (MNA-SF) scale. Direct relationships between number of teeth, nutrition and sarcopenia were assessed using multiple linear regression. Mediation models and structural equation model (SEM) pathway analysis were used to test the mediating role of nutrition in the relationship between number of teeth and sarcopenia. RESULTS: Of 4149 participants aged 50 years old or older, the prevalence of sarcopenia was 22.5, 9.0% for moderate sarcopenia, and 13.5% for severe sarcopenia, respectively. Regression analysis indicated a total association between number of teeth (ß = - 0.327, 95% CI - 0.471 to - 0.237, p < 0.001) and sarcopenia. After adjusted MNA-SF scores, the association between number of teeth and sarcopenia was still significant (ß = - 0.269, 95% CI - 0.364 to - 0.175, p < 0.001), indicating a partial mediation effect of nutrition. Mediation analysis verified nutrition partially mediate the associations between number of teeth and sarcopenia (indirect effect estimate = - 0.0272, bootstrap 95% CI - 0.0324 to - 0.0222; direct effect estimate = - 0.0899, bootstrap 95% CI - 0.1049 to - 0.0738). And this mediation effect was through impacting SMI (indirect effect estimate = - 0.0283, bootstrap 95% CI - 0.0336 to - 0.0232) and grip strength (indirect effect estimate = - 0.0067, bootstrap 95% CI - 0.0094 to - 0.0043). Structural equation model (SEM) framework pathway analysis confirmed the association between number of teeth, nutrition, and sarcopenia. CONCLUSIONS: Our findings indicated that sarcopenia was associated with number of teeth and poorer nutritional status, with nutrition partially mediating the association between number of teeth and sarcopenia. Our findings supported early nutritional assessment and intervention in oral health to mitigate the risk of sarcopenia.

Gut Microbiota Interact With the Brain Through Systemic Chronic Inflammation: Implications on Neuroinflammation, Neurodegeneration, and Aging.

It has been noticed in recent years that the unfavorable effects of the gut microbiota could exhaust host vigor and life, yet knowledge and theory are just beginning to be established. Increasing documentation suggests that the microbiota-gut-brain axis not only impacts brain cognition and psychiatric symptoms but also precipitates neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). How the blood-brain barrier (BBB), a machinery protecting the central nervous system (CNS) from the systemic circulation, allows the risky factors derived from the gut to be translocated into the brain seems paradoxical. For the unique anatomical, histological, and immunological properties underpinning its permeable dynamics, the BBB has been regarded as a biomarker associated with neural pathogenesis. The BBB permeability of mice and rats caused by GM dysbiosis raises the question of how the GM and its metabolites change BBB permeability and causes the brain pathophysiology of neuroinflammation and neurodegeneration (NF&ND) and brain aging, a pivotal multidisciplinary field tightly associated with immune and chronic systemic inflammation. If not all, gut microbiota-induced systemic chronic inflammation (GM-SCI) mainly refers to excessive gut inflammation caused by gut mucosal immunity dysregulation, which is often influenced by dietary components and age, is produced at the interface of the intestinal barrier (IB) or exacerbated after IB disruption, initiates various common chronic diseases along its dispersal routes, and eventually impairs BBB integrity to cause NF&ND and brain aging. To illustrate the immune roles of the BBB in pathophysiology affected by inflammatory or "leaky" IB resulting from GM and their metabolites, we reviewed the selected publications, including the role of the BBB as the immune barrier, systemic chronic inflammation and inflammation influences on BBB permeability, NF&ND, and brain aging. To add depth to the bridging role of systemic chronic inflammation, a plausible mechanism indispensable for BBB corruption was highlighted; namely, BBB maintenance cues are affected by inflammatory cytokines, which may help to understand how GM and its metabolites play a major role in NF&ND and aging.

Pan-mTOR inhibitors sensitize the senolytic activity of navitoclax via mTORC2 inhibition-mediated apoptotic signaling.

Compounds with senolysis activity are discovered in recent years, featuring by their capacity to specifically eliminate senescent cells in vitro or in vivo. These compounds, referring to as Senolytics, provide a new method for aging counteraction and probably for geriatric disease amelioration. However, their clinical application is unpractical still, mainly because of the safety issue. In fact, the effective dose range even of the most potent senolytic cannot guarantee the safety requirements application for human being. Here, we report a study which investigated the combinational application of one potential senolytic molecule navitoclax, a Bcl-2 inhibitor with several mTOR inhibitors, to assess the influence of this combination on the senolytic outcome. Our results reveal that pan-mTOR inhibitors can reduce the dosage or timespan of navitoclax necessary for reaching IC50 and LT50 in senescent cells, also extend the lifespan of premature-aged Drosophila and mitigate the aging-related phenotype. Our results also confirmed that mTOR inhibitor sensitized senolytic cell death is apoptotic and pan-mTOR inhibitors PP242 and AZD8055 works more effectively than mTORC1 inhibitor Rapamycin. Mechanically, we verified the crucial role of mTORC2 inhibition contributes sensitization by increasing the expression of the pro-apoptotic protein Bim. In summary, this study firstly exposes the sensitization effect of pan-mTOR inhibitors on navitoclax-induced senolytic apoptosis, therefore providing novel evidence to show the advantage of drug combination on setting senotherapy. It also provides an intriguing clue to demonstrate the value of mTORC2 inhibition for apoptotic death of senescent cells.

The mediation role of sleep quality in the relationship between cognitive decline and depression.

OBJECTIVES: Associations between cognitive decline and depression have been inconclusive. We examined 1) whether sleep quality mediates these relationships and 2) which factor of sleep quality mediates these relationships. METHODS: This study utilized baseline data from the 2018 West China Health and Aging Trend study (WCHAT), a large cohort data-set that including participants aged over 50 years old. We defined depression using the 15-item Geriatric Depression Scale (GDS-15). Cognitive status was measured using the Short Portable Mental Status Questionnaire (SPMSQ) and sleep quality was assessed using the Pittsburgh sleep quality index (PSQI). Direct relationships between cognitive decline, sleep quality and depression were assessed using multiple linear regression. Mediation models and structural equation model (SEM) pathway analysis were used to test the mediating role of specific aspects of sleep (e.g., quality, duration) in the relationship between cognitive decline and depression. RESULTS: Of 6828 participants aged 50 years old or older, the proportion of depression was 17.4%. Regression analysis indicated a total association between cognitive scores (ß = 0.251, 95% CI 0.211 to 0.290, p < 0.001) and depression status. After adjusted PSQI scores, the association between cognitive scores and depression status was still significant (ß = 0.242, 95% CI 0.203 to 0.281, p < 0.001), indicating a partial mediation effect of sleep quality. Mediation analysis verified sleep quality partially mediate the associations between cognitive decline and depression (indirect effect estimate = 0.0308, bootstrap 95% CI 0.023 to 0.040; direct effect estimate = 0.3124, bootstrap 95% CI 0.269 to 0.350). And daytime dysfunction had a highest mediation effect with a proportion of mediation up to 14.6%. CONCLUSIONS: Sleep quality partially mediated the relationship between cognitive decline and depression. Daytime dysfunction had a highest mediation effect. Further research is necessary to examine the effects of sleep quality on the relationship of cognitive decline and depression.

miR-146a impedes the anti-aging effect of AMPK via NAMPT suppression and NAD+/SIRT inactivation.

Nicotinamide adenine dinucleotide (NAD+) is indispensable for the anti-aging activity of the sirtuin (SIRT) family enzymes. AMP-activated protein kinase (AMPK) upregulates NAD+ synthesis and SIRT activity in a nicotinamide phosphoribosyltransferase (NAMPT)-dependent manner. However, the molecular mechanisms that affect AMPK-driven NAMPT expression and NAD+/SIRT activation remain unclear. In this study, we tried to identify senescence-associated microRNAs (miRNAs) that negatively regulate the cascade linking AMPK and NAMPT expression. miRNA-screening experiments showed that the expression of miR-146a increased in senescent cells but decreased following AMPK activation. Additionally, miR-146a overexpression weakened the metformin-mediated upregulation of NAMPT expression, NAD+ synthesis, SIRT activity, and senescence protection, whereas treatment with the miR-146a inhibitor reversed this effect. Importantly, these findings were observed both in vitro and in vivo. Mechanistically, miR-146a directly targeted the 3'-UTR of Nampt mRNA to reduce the expression of NAMPT. AMPK activators metformin and 5-aminoimidazole-4-carboxamide (AICAR) hindered miR-146a expression at the transcriptional level by promoting IκB kinase (IKK) phosphorylation to attenuate nuclear factor-kappaB (NF-κB) activity. These findings identified a novel cascade that negatively regulates the NAD+/SIRT pathway by suppressing miR-146a-mediated NAMPT downregulation. Furthermore, our results showed that miR-146a impedes the anti-aging effect of AMPK. This mutual inhibitory relationship between miR-146a and AMPK enriches our understanding of the molecular connections between AMPK and SIRT and provides new insight into miRNA-mediated NAD+/SIRT regulation and an intervention point for the prevention of aging and age-related diseases.

Higher uric acid serum levels are associated with sarcopenia in west China: a cross-sectional study.

BACKGROUND: Sarcopenia is the decline in muscle strength and mass attributed to aging. The pathogenesis of sarcopenia may be triggered by oxidative stress and uric acid (UA) has strong antioxidant properties. The aim of this study was to investigate the relationship between UA and sarcopenia in community-dwelling adults of West China using the baseline data of West China Health and Aging Trend (WCHAT) study. DESIGN: A cross-sectional study. METHODS: 4236 adults aged 50 years or older in communities of west China were enrolled in this study. We applied Asian Working Group for Sarcopenia (AWGS) 2019 criteria to define sarcopenia. Muscle mass was measured using skeletal muscle index (SMI) based on bioimpedance analysis (BIA). Handgrip strength (HGS) and gait speed (GS) were recorded, respectively. Different variables like anthropometry measures, life styles, chronic disease and blood test were collected. General linear model was done to investigate the relationship between UA and HGS/GS/SMI, adjusting age, ethnic groups, sleeping quality, education level, cognitive function, smoking history, drinking history, ADL score, and chronic disease. RESULTS: Participants were grouped according to UA quartiles by gender. After adjusting for potential confounders, a negative association between serum UA levels and sarcopenia was shown both in men and women. And a significant association between serum UA levels and HGS in women was shown as an inverted J shape. Besides, a positive association between the UA quartiles and SMI was observed, irrespective of gender. CONCLUSIONS: Our results showed that higher uric acid levels were significantly correlated with higher muscle mass and grip strength among Chinese adults aged over 50. Higher UA serum levels might slow down the progression of sarcopenia.

The prevalence and associated factors of motoric cognitive risk syndrome in multiple ethnic middle-aged to older adults in west China: a cross-sectional study.

BACKGROUND AND PURPOSE: Motoric cognitive risk (MCR) syndrome characterized by subjective cognitive complaints and slow gait has been proposed and validated as a pre-dementia syndrome. The overall and specific ethnic prevalence of MCR and the associated factors are poorly understood in middle-aged to older community-dwelling residents in west China. METHODS: The present study included 6091 samples from the prospective cohort study, West China Health and Aging Trend (WCHAT). Multidimensional factors of demography, lifestyle, social support, anthropometrics and body components, and clinical status were investigated and analyzed by univariate and multivariate logistic regression models. Lasso regression and K-fold cross-validation were conducted to construct the most predictive model with fitted factors. RESULTS: The overall prevalence of MCR was 9.74%, and ethnically the prevalence was 14.25% in Tibetan, 11.03% in Yi, 10.72% in Han, 5.18% in Uighur and 4.55% in Qiang, respectively. In the adjusted models, the positively associated risk factors included diabetes mellitus (odds ratio [OR] = 1.51, p = 0.007), osteoarthritis (OR = 1.50, p = 0.002), depression (OR = 1.36, p = 0.005), poor sleep (OR = 1.21, p = 0.045), comorbidity (OR = 1.49, p = 0.001) and falls in the last 12 months (OR = 1.34, p = 0.031). Of note, every 1-unit increase of value in stroke was associated with an approximate 3-fold higher risk of having MCR, whilst in high-density lipoprotein with a 30% lower risk of MCR,respectively. CONCLUSIONS: Profiles of MCR from the aspects of ethnicity and the presenium stage need further exploration. It is a promising strategy to apply MCR as a primary prevention tool to prevent dementia.

Comorbid anxiety and depression, depression, and anxiety in comparison in multi-ethnic community of west China: prevalence, metabolic profile, and related factors.

OBJECTIVES: To identify the prevalence, lifestyle factors, chronic disease status, and assessing the metabolic profile, comparing key differences in a cohort of subjects aged at least 50 years old among depression combined anxiety, depression and anxiety in a multi-ethnic population in west China. METHODS: A large multi-ethnic sample of 6838 participants aged 50 years old (mean age 62.4 ± 8.3 years) from West China Health and Aging Trend (WCHAT) study was analyzed. We categorized all participants into four groups: (a) comorbid anxiety and depression symptomology (CAD), (b) anxiety only, (c) depression only, or (d) neither depression nor anxiety. Different variables like anthropometry measures, life styles, chronic disease and blood test were collected. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale (GDS-15). GDS-15 scores ≥5 indicate depression. Anxiety status was assessed using Generalized Anxiety Disorder (GAD-7) instrument and the scores ≥5 was considered as having anxiety. Different variables like anthropometry measures, life styles, cognitive function and chronic disease comorbidities were collected and serum parameters were tested. Multivariable logistic regression adjusted for age, sex, and ethnicity was done to compare between those with the mental outcomes and without. RESULTS: The proportions of CAD, anxiety and depression were 9.0%, 12.8% and 10.6% respectively with ethnic diversity. The 'comorbid' group shown greater frequency of being female, having a lower educational level, higher prevalence of being single/divorced/widowed, drinking alcohol and smoking, more chronic disease profile and cognitive decline compared with individuals with only one disorder. And the metabolic profile showed differences in albumin, total protein, creatinine, uric acid, thyroid hormones in comparing CAD symptomology and the 'neither symptomology'. CONCLUSIONS: Yi, Qiang and Uyghur ethnic groups have a higher prevalence of mental disease compared with Han in west China. And these mental disease had a distinct risk factor profile in age, sex, educational level, chronic disease and cognitive function. Vitamin D levels were lower among those with mental disease compared to those without.

Nutrition status mediates the association between cognitive decline and sarcopenia.

In this study, we investigated whether nutrition status mediates the relationship between cognitive decline and sarcopenia. Sarcopenia was assessed in 4023 community-dwelling older adults from West China using the AWGS 2014 diagnostic criteria. Cognitive function and nutrition status were assessed using the 10-item Short Portable Mental Status Questionnaire (SPMSQ) and Mini Nutrition Assessment-Short Form (MNA-SF) scale, respectively. Mediation model regression analysis demonstrated that nutrition status was negatively associated with sarcopenia (ß = -0.521; 95% CI: -0.583 to -0.459). The indirect effects of cognitive decline on sarcopenia were significant after adjusting for age, sex, and ethnicity (ß = 0.015; 95% CI: 0.012 to 0.017), but the direct effects of cognitive decline on sarcopenia were not statistically significant after adding nutrition status as a parameter in the mediation model analysis (ß = -0.001; 95% CI: -0.008 to 0.005). Structural equation model (SEM) framework pathway analysis confirmed the association between nutrition status, cognitive decline, and sarcopenia. These findings demonstrate that the negative effects of cognitive decline on sarcopenia were mediated by nutrition status. We therefore postulate that maintaining a good nutrition status delays the negative effects of cognitive decline on sarcopenia in older adults.

The Comparison of Sarcopenia Diagnostic Criteria using AWGS 2019 with the Other Five Criteria in West China.

INTRODUCTION: The aim of this study was to investigate the prevalence and associated factors of sarcopenia defined by different criteria in community-dwelling adults of west China using the baseline data of West-China Health and Aging Trend (WCHAT) study. METHODS: Adults aged 50 years or older in communities of Yunnan, Guizhou, Sichuan, and Xinjiang provinces were enrolled in this study. We applied 6 -diagnostic criteria (AWGS 2019, AWGS 2014, EWGSOP1, -EWGSOP2, IWGS, and FNIH) to define sarcopenia. Muscle mass was measured based on bioimpedance analysis. Handgrip strength and walking speed were recorded, respectively. Different variables like anthropometry measures, lifestyles, chronic disease, and blood test were collected. RESULTS: We included 4,500 participants. The prevalence of sarcopenia was 22.8, 19.3, 57.1, 11.8, 24.1, and 18.1% according to the AWGS 2019, AWGS 2014, EWGSOP 1, EWGSOP 2, IWGS, and FNIH criteria, respectively. We found that serum albumin level was independently associated with sarcopenia using AWGS 2019 and IWGS. And vitamin D level was independently associated with sarcopenia using AWGS 2014, -EWGSOP2, and FNIH. While age, depressive status, BMI, hemoglobin, vitamin D, and insulin level were all significantly associated with sarcopenia using AWGS 2014, but all of these factors were not significant using AWGS 2019. CONCLUSIONS: Sarcopenia was highly prevalent in west China regardless of the diagnostic criteria. Serum albumin and vitamin D level were mostly associated with sarcopenia defined by different criteria. While most risk factors associated with the AWGS 2014-defined sarcopenia exhibited no consistent pattern with AWGS 2019, the validity of the AWGS 2019 consensus needs to be confirmed in further prospective studies.

Nrf2-SHP Cascade-Mediated STAT3 Inactivation Contributes to AMPK-Driven Protection Against Endotoxic Inflammation.

Signal transducer and activator of transcription 3 (STAT3) is implicated in inflammation processing, but the mechanism of its regulation mostly remains limited to Janus kinase (JAK)-mediated phosphorylation. Although AMP-activated protein kinase (AMPK)-mediated STAT3 inactivation has got documented, the molecular signaling cascade connecting STAT3 inactivation and the anti-inflammatory role of AMPK is far from established. In the present study, we addressed the interplay between AMPK and STAT3, and revealed the important role of STAT3 inactivation in the anti-inflammatory function of AMPK in lipopolysaccharide-stressed macrophages and mice. Firstly, we found that pharmacological inhibition of STAT3 can improve the anti-inflammatory effect of AMPK in wild-type mice, and the expression of STAT3 in macrophage of mice is a prerequisite for the anti-inflammatory effect of AMPK. As to the molecular signaling cascade linking AMPK to STAT3, we disclosed that AMPK suppressed STAT3 not only by attenuating JAK signaling but also by activating nuclear factor erythroid-2-related factor-2 (Nrf2), a redox-regulating transcription factor, which consequently increased the expression of small heterodimer protein (SHP), thus repressing the transcriptional activity of STAT3. In summary, this study provided a unique set of evidence showing the relationship between AMPK and STAT3 signaling and explored a new mechanism of AMPK-driven STAT3 inactivation that involves Nrf2-SHP signaling cascade. These findings expand our understanding of the interplay between pro- and anti-inflammatory signaling pathways and are beneficial for the therapeutic development of sepsis treatments.