To investigate the association of early-life exposure to famine with the risk of mortality in later life, as well as to assess the mediating effect of BMI in adulthood on the relationship between early-life famine exposure and long-term mortality risk. The China Health and Nutrition Survey (CHNS) served as the basis for the study’s data analysis. A total of 8,085 individuals participated in this study. All subjects were categorized into five groups: no exposure group, fetal exposure group, early childhood exposure group, mid-childhood exposure group, and late childhood exposure group. The association of famine exposure with mortality was analyzed using Cox proportional hazards regression models. Exposure to famine in mid-childhood and late childhood exposure was significantly associated with an increased mortality risk (HR: 2.453 and 3.016, 95

Background/Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, yet the association between folic acid (FA) intake and CRC risk remains controversial. This study investigated the effects of varying dietary FA levels on colorectal carcinogenesis and the underlying mechanisms. Methods: BALB/c mice were fed diets containing FA at <0.1, 2.0, 6.0, 8.0, or 20.0 mg/kg for 14 weeks. After 4 weeks, colorectal tumorigenesis was induced using the azoxymethane/dextran sulfate sodium (AOM/DSS) protocol. Tumor multiplicity, maximum tumor diameter, tumor volume, colorectal length, histopathology, and cell proliferation were assessed. Mechanistic assessments included uracil misincorporation, thymidylate synthase (TS), telomere attrition, genome-wide DNA methylation, RAP1 signaling, immune-related markers, and inflammatory cytokines in colorectal tissues. Results: Both FA deficiency (<0.1 mg/kg) and excess (8.0/20.0 mg/kg) increased colorectal tumor burden, with increased tumor number, larger maximum diameter, greater tumor volume, shortened colorectal length, and enhanced cell proliferation, whereas the 6.0 mg/kg diet group showed the lowest tumor burden. FA deficiency reduced TS expression, elevated deoxyuridine monophosphate (dUMP) levels, decreased deoxythymidine monophosphate (dTMP) levels, increased uracil misincorporation, and exacerbated telomere attrition, as evidenced by shortened telomeres and increased damage. In contrast, excessive FA intake induced Rap1 GTPase-activating protein (RAP1GAP) hypermethylation, reduced Rap1GAP expression, enhanced RAP1 activity, and upregulated programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) expression. Conclusions: Dietary FA can exhibit a U-shaped association with colorectal carcinogenesis, with protective effects observed within an optimal range. FA deficiency and excess may drive tumor development through distinct molecular pathways involving uracil misincorporation-induced telomere attrition and DNA methylation-mediated immunosuppression, respectively.

Dementia is a growing global health burden,with mild cognitive impairment(MCI)serving as a critical transitional stage[1].Identifying the nutritional risk factors is crucial for prevention.While nutrition plays a key role in preventing age-related diseases and staple foods are a major dietary source,existing research on cognitive function has predominantly emphasized whole-grain consumption.There is limited evidence regarding the effects of specific staple food types on MCI.

Cardiovascular disease develops through gradual accumulation of risk factors and progressive vascular damage. Longitudinal studies are well suited to determine when and how these changes occur, but they introduce several analytic challenges, including repeated measurements on the same individuals, irregular or sparse follow-up schedules, missing data, and non-linear trajectories. We conducted a narrative, application-focused review categorizing methods into five major classes: traditional or marginal models, mixed-effect models, joint models, trajectory and mixture models, and functional or machine-learning approaches. For each class, we provide intuitive descriptions, typical cardiovascular applications, and a balanced discussion of assumptions, strengths, limitations, and recommended sensitivity analyses. We emphasize practical guidance for method selection, model validation, and transparent reporting. In summary, no single method addresses every research goal. The analytic strategy should fit both the clinical question and data characteristics, with clear definition of objectives, careful assessment of assumptions, appropriate handling of missing data, and validation on independent samples whenever possible. Future methodological development should focus on making hybrid models more accessible, improving integration of sparse and dense data sources, and advancing reporting standards for longitudinal cardiovascular research.

Falls threaten the physical and mental health of older persons. Studies of the relationship between oral health and falls were fragmented in their selection of oral health indicators. We aimed to analyze whether and to what extent self-reported oral health was associated with falls among community-dwelling older adults in China. A cross-sectional study was conducted using data from physical examination and questionnaire survey for older adults in Tianjin, China. 2150 community-dwelling individuals aged 60 and older were included. Self-reported history of falls during the past year and oral health were collected using questionnaires. In the oral health index, fewer missing teeth, wearing dentures, no toothache, no bleeding gums, and brushing teeth at least twice a day were assigned as a score of 1, respectively. Oral health index was calculated by summing the scores of each item and ranged from 0 to 5, with higher scores indicating better oral health status. Logistic regression controlled for potential confounders was employed to analyze the association between oral health and falls. The prevalence of fall within the previous year was 12.6

BACKGROUND AND OBJECTIVES:Previous studies have linked famine exposure to the incidence of type 2 diabetes (T2D), yet its impact on diabetic microvascular complications (DMC) remains uncertain. This study aims to investigate the longitudinal association between early-life famine exposure and the risk of DMC in adult-hood among individuals with T2D. METHODS AND STUDY DESIGN:A retrospective cohort study was conducted among inpatients with T2D at Tianjin Medical University Chu Hsien-I Memorial Hospital from June 2014 to June 2022. The 2409 participants were divided into five famine exposure groups based on birth years: no exposure group (1962-1965), fetal period exposure group (1959-1961), early-childhood exposure group (1956-1958), mid-childhood exposure group (1953-1955), and late-childhood exposure group (1949-1952). RESULTS:Compared with those nonexposed, early-life famine exposure was associated with higher risks of incident overall DMC (HRtrend 1.134, 95% CI 1.052-1.223), diabetic retinopathy (DR) (HRtrend 1.193, 95% CI 1.100-1.293), and diabetic kidney disease (DKD) (HRtrend 1.262, 95% CI 1.117-1.425), but was not associated with diabetic neuropathy (p > 0.05). Notably, significant interactions were found between famine exposure and hypertension regarding the risk of DR, and between famine exposure and both and obesity patterns on the risk of DKD (all p for interaction < 0.05). CONCLUSIONS:Exposure to famine in early life was associated with increased risks of overall DMC, DR and DKD among patients with T2D. Specially, the association of DR was more pronounced in individuals with hypertension, while the association with DKD was stronger among those with hypertension or both general and abdominal obesity.

OBJECTIVE:To assess the efficacy of the reducing cardiometabolic disease risk (RCMDR) dietary pattern health education intervention on cardiometabolic disease (CMD) risk and carotid atherosclerosis in the Chinese older population. DESIGN:The cluster randomized clinical trial was conducted from April 2023 to December 2024. Participants according to residential areas were randomized to the intervention group (2 clusters) or control group (2 clusters). SETTING:Single-center in Tianjin, China. PARTICIPANTS:694 community older residents (61-80 years): intervention group (n = 349) and control group (n = 345). INTERVENTION:Participants in the intervention group received the RCMDR dietary pattern health education intervention, while those in the control group received general health education. The intervention period lasted 12 months. MEASUREMENTS:The primary outcome was clustered cardiometabolic risk score (CMRS). The secondary outcomes included common carotid artery ultrasound parameters and cardiometabolic risk indicators. Analysis was intention-to-treat principle. RESULTS:Of 694 participants, 411 (59.2%) were female; mean (SD) age was 68.2 (5.1) years. Compared with the control group, the RCMDR dietary pattern health education intervention resulted in a significantly lower CMRS (β = -0.25; 95% CI -0.31, -0.19); lower intima-media thickness (β = -0.05, 95% CI -0.08, -0.02); lower serum total cholesterol, triglyceride and low-density lipoprotein cholesterol, higher high-density lipoprotein cholesterol; lower fasting blood glucose, fasting insulin, fasting C-peptide and HOMA-IR, higher HOMA-β; lower serum homocysteine; lower systolic blood pressure and diastolic blood pressure; lower weight, body mass index, waist circumference, waist-to-hip ratio, body fat percentage, body fat mass and Chinese visceral adiposity index, higher lean body mass (all P < 0.05). CONCLUSION:The RCMDR dietary pattern health education intervention could reduce the CMD risk, delayed the progression of carotid atherosclerosis and improved cardiometabolic factors among Chinese older population.

Symptomatic knee osteoarthritis (KOA) and muscle-related disorders are prevalent and interrelated among middle-aged and elderly people. Serum creatinine/cystatin C (Cr/CysC) ratio is a promising biomarker for identifying low muscle mass or sarcopenia. The aim of this study was to investigate the association between serum Cr/CysC and the incident risk of symptomatic knee osteoarthritis in Chinese middle-aged and older adults, considering sex variations. This prospective cohort study included 4155 participants aged ≥ 45 years from the 2011 and 2015 waves of the China Health and Retirement Longitudinal Study (CHARLS). Cr/CysC ratio was calculated by serum creatinine (mg/dL)/cystatin C (mg/L) *100. The incidence of symptomatic KOA was defined as participants who were free of symptomatic KOA at baseline and diagnosed with symptomatic KOA at the 4-year follow-up. Logistic regression models were used to explore the relationship between Cr/CysC ratio and incidence of KOA in both sexes. Restricted cubic analysis was employed to analyze the nonlinear relationship. Then, 420 participants (10.1

Adequate micronutrients play a crucial role in cognitive health. Identifying relevant micronutrients and constructing risk prediction models can guide the prevention of mild cognitive impairment (MCI) in older adults. This study aimed to assess the associations of MCI with whole blood micronutrient levels and develop a nomogram for personalized MCI risk prediction in older adults. In the matched case–control study, 100 MCI patients and 100 matched controls by age, sex and education from Baodi District, Tianjin, China were recruited. MCI was determined by a modified version of the Petersen criteria. Whole blood levels of 9 vitamins and 5 minerals were measured using the dried blood spot technique. Weighted quantile sum regression was employed to identify the most significant micronutrients associated with cognitive function. Receiver operating characteristic (ROC) curves were constructed, and a nomogram for predicting MCI risk was developed. High levels of vitamins (vitamin A, vitamin B2, vitamin B6, vitamin B9) and minerals (magnesium, selenium) were significantly associated with lower MCI prevalence, in which vitamin B2, vitamin B9 and selenium were ranked as the most significant contributors to cognitive function. The ROC curves for vitamin B2 and vitamin B9 (area under the curve = 0.855) have superior diagnostic accuracy compared to individual assessments (p < 0.05). Based on these findings, a nomogram was developed using these two micronutrients to predict MCI risk. The nomogram based on vitamin B2 and vitamin B9 can be effectively used to detect MCI early and guide preventive strategies in older adults.

Increasing evidence has shown that there was an association between arthritis and metabolism and circadian rhythms. Circadian syndrome (CircS) can serve as an overarching indicator of circadian and metabolic disturbances. However, there are limited studies investigating the longitudinal association between the symptomatic knee arthritis and circadian syndrome (CircS). This study used the data from two waves (2011 and 2015) of the China Health and Retirement Longitudinal Study (CHARLS). CircS was diagnosed when participants exhibited four or more of the following specified components: short sleep, depression, abdominal obesity, hyperglycemia, hypertension, and dyslipidemia. Symptomatic knee arthritis was diagnosed when both concurrent pain in knee joint and physician-diagnosed arthritis existed. Individuals diagnosed with CircS in 2011 were excluded from the symptomatic knee arthritis group, and those with symptomatic knee arthritis in 2011 were excluded from the CircS group. Each group was followed up for four years to observe the incidence of CircS and symptomatic knee arthritis, respectively. Binary logistic regression models were used to estimate the odds ratios (ORs) and 95

BACKGROUND:Medium-chain triglycerides (MCT) and docosahexaenoic acid (DHA) could affect cognitive function, but their combination effects remain unclear. This randomized, double-blind, placebo-controlled trial aimed to evaluate effects of MCT and DHA supplementation, alone or in combination, on mild cognitive impairment (MCI) patients. METHODS:A total of 280 MCI participants were randomly assigned to the placebo group, MCT group (14 g/d octanoic acid+10 g/d capric acid), DHA group (800 mg/d) and MCT + DHA (14 g/d octanoic acid, 10 g/d capric acid and 800 mg/d DHA) group, 70 individuals per group for 12 months. Cognitive function was assessed at baseline, 6 months and 12 months; blood indicators were analyzed at baseline and 12 months. This study is registered with Chinese Clinical Trial Registry (ChiCTR2200059641). RESULTS:After 12 months intervention, compared with the placebo group, MCT group, DHA group and MCT + DHA group had statistically significant improvements in full scale IQ (β: 0.107, 95 % CI: 0.006, 0.208; β: 0.135, 95 % CI: 0.034, 0.235; β: 0.136, 95 % CI: 0.035, 0.237), serum total ketone body levels (β: 10.540, 95 % CI: 9.550, 11.531; β: 5.884, 95 % CI: 4.894, 6.875; β: 13.186, 95 % CI: 12.196, 14.176), and decreases in mtDNA deletions (β: -0.370, 95 % CI: -0.648, -0.092; β: -0.335, 95 % CI: -0.613, -0.056; β: -0.427, 95 % CI: -0.705, -0.148) and plasma Aβ42 levels (β: -3.318, 95 % CI: -5.571, -1.064; β: -3.218, 95 % CI: -5.472, -0.965; β: -2.906, 95 % CI: -5.160, -0.653). CONCLUSIONS:Supplementation of MCT, DHA and their combination for 12 months can significantly improve cognitive function, mitochondria function and increase serum total ketone body levels in MCI individuals. Combined intervention was more beneficial than MCT or DHA alone.

BACKGROUND:The reference intervals (RIs) for venous whole blood micronutrients are instrumental in evaluating nutritional status within populations. However, research on establishing micronutrient RIs using the simple and efficient dried blood spot (DBS) technique remains scarce. Consequently, this study aims to establish RIs for venous whole blood micronutrients among healthy Chinese older individuals via DBS. METHODS:Participants were recruited from the general community of Baodi District, Tianjin, northern China. Healthy populations were identified based on the recommendations of the Clinical and Laboratory Standards Institute guidelines, physical signs (body mass index and waist circumference), and blood biochemical parameters (serum lipid status and hemoglobin). The micronutrient levels were measured via the DBS technique. For normally distributed data, the RI was calculated as the mean ± 2SD. For non-normally distributed data, the RI is calculated as the 2.5th to 97.5th percentiles. RESULTS:This study established RIs for 8 vitamins (vitamins A, D, E, B1, B2, B3, B6, B9) and 5 minerals (Mg, Cu, Fe, Zn, Se) in healthy older adults. For males, the RIs are as follows: VA (157.76-828.81 ng/mL); VD (8.89-58.32 ng/mL); VE (1.84-13.78 μg/mL); VB1 (0.19-5.36 ng/mL); VB2 (0.53-13.84 ng/mL); VB3 (4.43-13.70 μg/mL); VB6 (1.09-26.00 ng/mL); VB9 (1.02-9.48 ng/mL); Mg (27.54-52.99 mg/L); Cu (0.57-1.64 mg/L); Fe (287.00-708.60 mg/L); Zn (4.10-20.85 mg/L); Se (70.57-167.63 μg/L). For females: VA (142.62-755.78 ng/mL); VD (10.10-66.20 ng/mL); VE (1.87-13.43 ng/mL); VB1 (0.15-4.20 ng/mL); VB2 (0.61-12.81 ng/mL); VB3 (4.51-15.53 ng/mL); VB6 (1.82-24.05 ng/mL); VB9 (0.60-9.62 ng/mL); Mg (25.73-51.94 mg/L); Cu (0.58-1.41 mg/L); Fe (236.75-599.81 mg/L); Zn (3.93-22.22 mg/L); Se (70.57-167.63 μg/L). CONCLUSIONS:This study presents venous whole blood micronutrient parameters that can facilitate nutrition-related epidemiological research and inform personalized intervention strategies, thereby enhancing the quality of healthcare for elderly individuals in China.

Background: Phosphatidylserine (PS) and alpha-Linolenic acid (ALA), are positively associated with cognitive function, but their combination effects and possible mechanisms remain unclear. We aimed to explore the effects on cognition and potential mechanism of the supplements. Methods: This randomized, double-blind, placebo-controlled trial recruited 190 MCI patients in Tianjin, China, and randomly assigned in intervention group and placebo group. Each group consumed two capsules every day for 12 months. Each capsule for intervention group contains 144 mg ALA, 31.5 mg PS and 3.6 mg Ginkgo total flavonoids as main functional components, with 0.48 mg Vitamin B1 (as thiamine hydrochloride), 0.48 mg Vitamin B6 (as pyridoxine hydrochloride) and 90 mu g folic acid as supplement. Capsules for placebo group were identical but contain no active ingredients. Cognitive function, serum n-3 polyunsaturated fatty acids (PUFAs) and neurotransmitters were assessed at baseline and 12 months. Linear mixed effects model and causal mediation analysis were conducted to explore the effects and potential mechanism of the intervention. Results: A total of 190 participants (mean [SD] age, 67.95 [5.62] years; 70 (36.8 %) male and 120 (63.2 %) female) were randomized to the placebo group (n = 95) and intervention group (n = 95). Compared with placebo group, the intervention group had statistically significant improvements in arithmetic testing (/3, 0.688; 95 % CI, 0.103-1.274), the similarity test (/3, 1.070; 95 % CI, 0.472-1.667) and short-term memory (/3, 0.600; 95 % CI, 0.399-0.800). Besides, the intervention group had statistically significant increases in serum ALA (/3, 1.620; 95 % CI, 0.967-2.265), DHA (/3, 2.797; 95 % CI, 1.075-4.532), EPA (/3, 1.472; 95 % CI, 0.296-2.643), acetylcholine (/3, 0.441; 95 % CI, 0.415-0.468), GABA (/3, 0.009; 95 % CI, 0.001-0.016) and 5-HT (/3, 0.160; 95 % CI, 0.081-0.238) compared to the placebo group. And the intervention may improve short-term memory by increasing serum ALA levels (average causal mediation effect = 0.132, 95 % CI, 0.053-0.225) with 19.7 % mediation proportion. Conclusions: This food supplement containing phosphatidylserine could improve different cognitive functions of MCI patients, especially short-term memory, and increase serum n-3 PUFAs and neurotransmitters levels. Serum ALA level might play a mediation role.

BACKGROUND AND OBJECTIVES:Systemic lupus erythematosus (SLE) is an autoimmune disease with unknown etiology. For newly diagnosed SLE, there are few studies analyzing whether the use of belimumab can reduce the dose of glucocorticoids while maintaining disease remission. To explore this, we conducted this single-center, real-world setting study, based on a prospective cohort. METHODS:Newly diagnosed SLE taking Belimumab and standard-of-care (SoC) treatment were consecutively enrolled from July 2021 to December 2023 in a prospective manner. Disease assessments (SLE Responder Index 4 (SRI-4) response (a composite indicator to evaluate the efficacy of belimumab in RCTs), SLEDAI-2K) were conducted regularly. Patients were followed up for at least 12 months. Matched patients with SoC alone were enrolled after propensity score matching. Difference examination and generalized estimated equations were conducted. RESULTS:A total of 31 patients were enrolled in Belimumab group. SRI-4 response rate was 87.10% at 12 months. Serological parameters (anti-dsDNA and C3/C4), SLEDAI-2K and daily prednisone intake were improved overall. Compared with SoC group, SRI-4 rate and the trends of complement C4, SLEDAI-2K during follow up was similar in two groups. Trends of complement C3 (13.16 (4.14-22.18), P=0.004), anti-dsDNA titer (-60.29 (-103.95 to -16.63), P=0.007) and prednisone intake (-18.59 (-26.88 to -10.30), P=0.000) were more significantly in Belimumab group. Belimumab group had significantly lower cumulative prednisone intake with overall well-tolerance. CONCLUSION:Our data supported that prompt initiation of add-on Belimumab should be considered to control the disease and facilitate GC tapering/discontinuation, without prior failure to one or more conventional drugs.

Concerns have been raised about potential hazards associated with folic acid fortification. This study aimed to explore associations between diverse folic acid fortification policies (mandatory vs. no mandatory fortification) and global late-onset colorectal cancer (LOCRC) incidence rates. The study systematically assessed (i) folic acid fortification policies in 193 member states of the World Health Organization, and (ii) age-standardized LOCRC incidence rates by country. We examined the associations between folic acid fortification types and LOCRC incidence using an ecological study design. Incidence trends before and after fortification were analyzed using a log-linear joinpoint regression model, and the annual percent change and average annual percent change with 95% confidence interval were determined for representative countries with mandatory fortification (the United States [U.S.] and Canada). By September 2024, 69 countries enacted mandatory folic acid fortification legislation, while 124 had no fortification. The overall LOCRC incidence rates per 100,000 were 70.8 and 84.0 with mandatory and no mandatory fortification, respectively. The decreasing trends after implementing folic acid fortification were more rapid than in the pre-fortification period in the U.S. and Canada. These findings suggested an association between mandatory folic acid fortification policies and reduced LOCRC incidence. These global data provide a scientific basis for transitioning fortification policies and inform strategies for cancer prevention through the fortification with folic acid.

Background: There is no specific dietary pattern for cardiometabolic health based on Chinese food culture. Objectives: The study aimed to develop and assess the efficacy of the reducing cardiometabolic disease risk (RCMDR) dietary pattern on cardiometabolic disease risk in the Chinese population with dyslipidemia. Methods: In this single-center, open-label, randomized, 12-wk dietary intervention study, 100 adults aged 35-45 y with dyslipidemia were randomly assigned (1:1) to the RCMDR dietary pattern intervention or general health education control group. Results: Compared with the control group, the RCMDR dietary pattern intervention resulted in a significantly lower clustered cardiometabolic risk score (primary outcome) ((3:-0.17; 95% CI:-0.29,-0.05); diastolic blood pressure ((3:-0.23; 95% CI:-0.40,-0.07); total cholesterol, LDL cholesterol, triglyceride ((3:-0.27; 95% CI:-0.49,-0.04; (3:-0.24; 95% CI:-0.41,-0.07; and (3:-0.19; 95% CI:-0.35,-0.04, respectively); homocysteine ((3:-0.19; 95% CI:-0.28,-0.09); waist circumference, waist-to-hip ratio, body fat percentage, body fat mass, visceral adipose tissue, visceral fat area, and a significantly higher lean body mass ((3:-1.12; 95% CI:-1.65,-0.59; (3:-1.01; 95% CI:-1.66,-0.36; (3:-1.43; 95% CI:-1.87,-0.98; (3:-0.98; 95% CI:-1.35,-0.60; (3:-1.93; 95% CI:-2.75,-1.11; (3:-6.52; 95% CI:-9.10,-3.95; and (3: 1.24; 95% CI: 0.84, 1.65, respectively). Conclusions: Compared with the control group, the RCMDR dietary pattern intervention lowers cardiometabolic risk, blood lipids, blood pressure, abdominal obesity, and circulating homocysteine concentration among Chinese population with dyslipidemia. Clinical Trial Registry: This trial was registered at Chinese Clinical Trial Registry as ChiCTR2300072472 (https://www.chictr.org.cn/showproj.html? proj=198618).

Total cholesterol (TC) and the cholesterol oxidation product 27-hydroxycholesterol (27-OHC) are both increased in the elderly. Accumulating evidence has linked 27-OHC to glucose metabolism in the brain, while docosahexaenoic acid (DHA) has been shown to positively regulate the 27-OHC levels. However, it is unclear whether DHA may affect glucose metabolism in the brain by regulating 27-OHC levels. In this study, we hypothesized that DHA supplementation would modulate TC levels and reduce 27-OHC levels, thereby improving brain glucose metabolism in SAMP8 mice. The mice were assigned into the Control group and DHA dietary supplementation group. The study evaluated cholesterol levels, 27-OHC levels, and glucose metabolism in the brain. The results showed that DHA supplementation decreased serum levels of TC, low-density lipoprotein cholesterol (LDL-C), and increased levels of high-density lipoprotein cholesterol (HDL-C); and improved the glucose-corrected standardized uptake value of cortex, hippocampus, and whole brain regions in SAMP8 mice. In conclusion, supplementation of DHA could regulate the cholesterol composition and reduce the level of 27-OHC, thereby improving brain glucose metabolism in SAMP8 mice.

BACKGROUND: The sympathoadrenergic system and its major effector PKA (protein kinase A) are activated to maintain cardiac output coping with physiological or pathological stressors. If and how PKA plays a role in physiological cardiac hypertrophy (PhCH) and pathological CH (PaCH) are not clear. METHODS: Transgenic mouse models expressing the PKA inhibition domain (PKAi) of PKA inhibition peptide alpha (PKIalpha)-green fluorescence protein (GFP) fusion protein (PKAi-GFP) in a cardiac-specific and inducible manner (cPKAi) were used to determine the roles of PKA in physiological CH during postnatal growth or induced by swimming, and in PaCH induced by transaortic constriction (TAC) or augmented Ca 2+ influx. Kinase profiling was used to determine cPKAi specificity. Echocardiography was used to determine cardiac morphology and function. Western blotting and immunostaining were used to measure protein abundance and phosphorylation. Protein synthesis was assessed by puromycin incorporation and protein degradation by measuring protein ubiquitination and proteasome activity. Neonatal rat cardiomyocytes (NRCMs) infected with AdGFP (GFP adenovirus) or AdPKAi-GFP (PKAi-GFP adenovirus) were used to determine the effects and mechanisms of cPKAi on myocyte hypertrophy. rAAV9.PKAi-GFP was used to treat TAC mice. RESULTS: (1) cPKAi delayed postnatal cardiac growth and blunted exercise-induced PhCH; (2) PKA was activated in hearts after TAC due to activated sympathoadrenergic system, the loss of endogenous PKIα (PKA inhibition peptide α), and the stimulation by noncanonical PKA activators; (3) cPKAi ameliorated PaCH induced by TAC and increased Ca 2+ influxes and blunted neonatal rat cardiomyocyte hypertrophy by isoproterenol and phenylephrine; (4) cPKAi prevented TAC-induced protein synthesis by inhibiting mTOR (mammalian target of rapamycin) signaling through reducing Akt (protein kinase B) activity, but enhancing inhibitory GSK-3α (glycogen synthase kinase-3α) and GSK-3β signals; (5) cPKAi reduced protein degradation by the ubiquitin-proteasome system via decreasing RPN6 phosphorylation; (6) cPKAi increased the expression of antihypertrophic atrial natriuretic peptide (ANP); (7) cPKAi ameliorated established PaCH and improved animal survival. CONCLUSIONS: Cardiomyocyte PKA is a master regulator of PhCH and PaCH through regulating protein synthesis and degradation. cPKAi can be a novel approach to treat PaCH.

Background: The physical abilities of older adults decline with age, making them more susceptible to micronutrient deficiency, which may affect their sleep quality. Objectives: This study aimed to construct a risk correlative model for sleep disorders in Chinese older adults based on blood micronutrient levels. Methods: In this matched case-control study, we recruited 124 participants with sleep disorders and 124 matched controls from the Tianjin Elderly Nutrition and Cognition cohort in China. Micronutrient levels in whole blood were measured using the dried blood spot technique. We compared the differences in micronutrient levels between the two groups and also constructed a receiver operating characteristic (ROC) model and nomogram for sleep disorders. Results: In comparison to the control group, the sleep disorders group showed lower levels of blood vitamin A, vitamin E (VE), folate, magnesium, copper, iron, and selenium (Se) in the univariate analysis (p < 0.05). The ROC curve analysis indicated that the combination of VE + folate + Se may have an excellent diagnostic effect on sleep disorders, with an area under the curve of 0.964. This VE + folate + Se was integrated into a nomogram model to demonstrate their relationship with sleep disorders. The consistency index of the model was 0.88, suggesting that the model assessed sleep disorders well. Conclusions: The sleep disorders risk correlative model constructed by the levels of VE, folate, and Se in whole blood might show good performance in assessing the risk of sleep disorders in older adults.

Background Little was known about whether Creatinine to Cystatin C Ratio (CCR) can predict the occurrence of symptomatic knee osteoarthritis (KOA). We examined the association between CCR and incident KOA and sex differences among Chinese middle-aged and older adults. Methods We included 4,155 participants aged ≥ 45 years in the 2011 and 2015 wave of the China Health and Retirement Longitudinal Study (CHARLS). The incident of symptomatic KOA was defined as participants who were free of symptomatic KOA at baseline and diagnosed with symptomatic KOA at the 4-year follow-up. Logistic regression models were used to explore the relationship between CCR and incidence KOA in both sexes. Restricted cubic analysis was employed to analyze non-linear relationship. Results 420 participants (10.1%) developed KOA during 4-year follow-up. The multivariable-adjusted odds ratio (OR) for KOA was 0.85 (95% confidence interval (CI), 0.74 to 0.98) per 1 standard deviation (SD) higher of CCR. The significant effect modification by sex was observed (P-interaction = 0.013). The highest tertile of CCR was significantly correlated with a lower incidence of symptomatic KOA in males (OR = 0.50, 95% CI = 0.29–0.88, P = 0.015), but not in females (OR = 0.88, 95% CI = 0.61–1.29, P = 0.522) compared with the lowest tertile. Significant non-linear relationship was identified for male with 75.0 of CCR being an inflection point. Conclusions Our findings provided new insights that CCR could serve as a promising biomarker for early KOA screening among Chinese males.