BACKGROUND:Peroxisome proliferators-activated receptor gamma co-activator 1α(PGC-1α)is closely related to aging and plays an important regulatory role in exercise anti-aging.However,there is a lack of comprehensive reviews on the role of PGC-1α in exercise anti-aging from the perspective of different tissues and organs. OBJECTIVE:To provide a detailed overview of the role of PGC-1α in exercise anti-aging and discuss its regulation from the perspective of different tissues and organs. METHODS:A literature search was conducted from May 1,2023 to July 1,2023.The search covered self-built databases up to July 2023,as well as databases such as Web of Science,PubMed,China National Knowledge Infrastructure(CNKI),WanFang,and VIP.The Chinese search terms included"PGC-1α,peroxisome proliferators-activated receptor gamma co-activator 1α,PPARGC1A,aging,exercise,older adults".The English search terms were"PGC-1α,aging,exercise,exercise training,older adults".Boolean logical operators were used to connect the search terms,and corresponding search strategies were developed.Based on inclusion and exclusion criteria,83 articles were included in the review. RESULTS AND CONCLUSION:(1)PGC-1α is an important transcriptional coactivator that plays a key regulatory role in maintaining mitochondrial function,regulating energy metabolism,and adapting to different metabolic demands.(2)PGC-1α has a significant regulatory role in mitochondrial aging and various functions in multiple cell types,and is associated with inflammatory pathways,redox control,protein modifications,and epigenetic changes.(3)The expression level of PGC-1α can be increased by exercise training,and it exerts positive effects through regulating mitochondrial biogenesis,energy metabolism,and anti-oxidative stress pathways.It plays an important role in exercise-induced improvement of adipose tissue aging,cardiovascular aging,neurosystem aging,renal aging,skeletal muscle aging,and liver aging.(4)The expert group recommends future research directions including exploring the regulatory effects of different types,intensities,and durations of exercise on PGC-1α expression,studying the regulatory mechanisms of protein modifications and epigenetic changes in PGC-1α, and strengthening the research on the mechanisms of PGC-1α in different aging-related diseases.

Objective:To investigate the expression of Toll-like receptor 4(TLR4)and extracellular signal-regulated protein kinase 1/2(ERK1/2)in decidua tissue of patients with unexplained spontaneous abortion and their correlation.Methods:The expres-sions of TLR4,ERK1/2 and p-ERK1/2 in decidua tissues of 32 patients with unexplained spontaneous abortion(abortion group)and 32 normal pregnancy(control group)were detected by immunohistochemistry and Western blot,respectively.The correlation between TLR4 and p-ERK1/2 in abortion group were analyzed by Pearson hierarchical correlation analysis.Results:In immunohistochemical experiments,the cytoplasm of decidua cells in the two groups is the expression locus of TLR4,ERK1/2 and p-ERK1/2,the expression of the three proteins were different,and the expressions of TLR4 and p-ERK1/2 in abortion group were significantly higher than that in control group(P<0.01).There was no significant difference in ERK1/2 expression between abortion group and control group(P>0.05);In decidua tissue samples of abortion group,the protein level of TLR4 was higher than that of control group(P<0.05);the pro-tein level of p-ERK1/2 was significantly higher than that of control group(P<0.01),and the protein level of ERK1/2 in decidua tissue of abortion group was not statistically different from that of control group(P>0.05).TLR4 was positively correlated with p-ERK1/2 expression in abortion group(r=0.890,P<0.01).Conclusion:Abnormal activation of TLR4/ERK1/2 signaling pathway may be one of the mechanisms of unexplained spontaneous abortion.

Objective:To establish the prediction model for postoperative delirium in elderly patients with mild stroke undergoing non-cardiac and non-intracranial surgery.Methods:This was a nested case-control study. Seven hundred and fifty elderly patients of either sex with mild stroke, aged ≥65 yr, undergoing elective surgical procedures under general anesthesia in the Department of Gastrointestinal Surgery, Orthopedics and Urology at the Tangshan Workers Hospital from May to December 2023, were selected. The perioperative clinical data were collected. The incidence of postoperative delirium was assessed using the Confusion Assessment Scale 1-7 days after surgery or 1 day before discharge. The patients were assigned to the training set and the validation set in a ratio of 7∶3 using a simple random sampling method. Multivariate logistic regression was used to identify the risk factors for postoperative delirium, a postoperative delirium risk prediction model was established based on the risk factors, the nomogram was developed, and the receiver operating characteristic (ROC) curve, calibration curve and decision curve were plotted to assess the accuracy of the prediction model. The prediction model was verified using the validation set, and the calibration curve and ROC curve were plotted to assess the predictive performance of the model.Results:A total of 721 patients were finally included, and 108 patients developed postoperative delirium. Older age, high American Society of Anesthesiologists Physical Status classification, history of preoperative hypertension, short years of education, high preoperative Pittsburgh sleep quality index score, high preoperative National Institutes of Health Stroke Scale score, high intraoperative hypothermia, intraoperative hypotension and high postoperative numerical rating scale score were independent risk factors for postoperative delirium ( P<0.05). The area under the ROC curve of the training set prediction model was 0.996, with a sensitivity of 1.000, and specificity of 0.945. The slope of the calibration curve was close to 1, and the predicted risk of postoperative delirium was in good agreement with the actual risk. When the threshold probability of the decision curve was 0-0.9, the net return rate was higher than the null line. Validation set: In the calibration curve of the prediction model, the cohort and calibration curves were close to the ideal line, with an area under the ROC curve of 0.997, sensitivity of 1.000, and specificity of 0.962. Conclusions:Based on age, American Society of Anesthesiologists Physical Status classification, history of preoperative hypertension, years of education, preoperative Pittsburgh sleep quality index score, National Institutes of Health Stroke Scale score, intraoperative hypothermia and hypotension and postoperative numerical rating scale score, the prediction model for postoperative delirium is developed and has a good predictive performance in elderly patients with mild stroke undergoing non-cardiac and non-intracranial surgery.

Background/Aims: The utility of Baveno-VII criteria of clinically significant portal hypertension (CSPH) to predict decompensation in compensated advanced chronic liver disease (cACLD) patient needs validation. We aim to validate the performance of CSPH criteria to predict the risk of decompensation in an international real-world cohort of cACLD patients. Methods: cACLD patients were stratified into three categories (CSPH excluded, grey zone, and CSPH). The risks of decompensation across different CSPH categories were estimated using competing risk regression for clustered data, with death and hepatocellular carcinoma as competing events. The performance of “treating definite CSPH” strategy to prevent decompensation using non-selective beta-blocker (NSBB) was compared against other strategies in decision curve analysis. Results: One thousand one hundred fifty-nine cACLD patients (36.8% had CSPH) were included; 7.2% experienced decompensation over a median follow-up of 40 months. Non-invasive assessment of CSPH predicts a 5-fold higher risk of liver decompensation in cACLD patients (subdistribution hazard ratio, 5.5; 95% confidence interval, 4.0–7.4). “Probable CSPH” is suboptimal to predict decompensation risk in cACLD patients. CSPH exclusion criteria reliably exclude cACLD patients at risk of decompensation, regardless of etiology. Among the grey zone, the decompensation risk was negligible among viral-related cACLD, but was substantially higher among the non-viral cACLD group. Decision curve analysis showed that “treating definite CSPH” strategy is superior to “treating all varices” or “treating probable CSPH” strategy to prevent decompensation using NSBB. Conclusions Non-invasive assessment of CSPH may stratify decompensation risk and the need for NSBB in cACLD patients.

Objective:To investigate the effects of urinary nickel exposure on insulin resistance, islet function and diabetes risk in adults aged 18 years and above in China.Methods:Based on the China National Human Biomonitoring from 2017 to 2018, a total of 500 diabetes patients were randomly selected as the case group, and the matched euglycemic control were selected by 1∶1 matching ratio. The urinary and venous blood samples of the subjects were collected, and the urinary nickel levels and serum glucose metabolism indexes such as fasting blood glucose and fasting insulin were detected, and the insulin resistance index (HOMA-IR), β cell function index (HOMA-β), and adjusted HOMA-β were calculated by using homeostasis model assessment. A multivariate logistic regression model was used to analyze the association between urinary nickel level and diabetes risk. Multiple linear regression models were used to evaluate the association of urinary nickel level with HOMA-IR, HOMA-β and adjusted HOMA-β.Results:The sex ratio of controls and cases was 1∶1. The multivariate logistic regression model showed that after adjusting for factors such as education level, smoking status, alcohol consumption, rice and meat intakes, family history of diabetes, BMI, total cholesterol level, hypertension, and urinary creatinine, compared with T1 group, the ORs of diabetes risk in the T2 and T3 groups were 1.36 (95% CI: 0.98-1.89) and 1.60 (95% CI: 1.14-2.24), respectively. The multiple linear regression model showed a positive association between urinary nickel levels and the elevated HOMA-IR, the β value of HOMA-IR in the T3 group was 0.12 (95% CI: 0.01-0.25) compared with the T1 group and each one-unit increase in the log-transformed urinary nickel level (2.71 μg/L) was associated with a 0.06 elevation in HOMA-IR (95% CI: 0.02-0.10). Meanwhile, the urinary nickel levels were negative associated with the adjusted HOMA-β, the β value of adjusted HOMA-β in the T3 group were -0.26 compared with the T1 group (95% CI: -0.41- -0.11), and each one-unit increase in the log-transformed urinary nickel level (2.71 μg/L) was associated with a -0.09 decrease in adjusted HOMA-β(95% CI: -0.14- -0.04). Conclusion:Higher urinary nickel level is positively correlated with elevated insulin resistance and diabetes risk while negatively correlated with the function of pancreatic islet β cells in adults in China.

Background::The heavy metals cadmium (Cd) and mercury (Hg) are known to be widespread environmental contaminants and high occupational exposure adversely affects the risk of chronic kidney disease (CKD). However, evidence from epidemiological studies linking low Cd and Hg exposure (or non-industrial) to the risk of progression to CKD are conflicting. This study aimed to explore the association of low Cd and Hg exposure with the risk of CKD in Chinese adults aged ≥80 years.Methods::The participants were recruited for the Healthy Aging and Biomarkers Cohort Study in 2017, an ongoing perspective survey conducted in longevity areas in China initially involving 3016 older adults. We used logistic regression models to estimate odds ratios (ORs) with 95% confidence intervals of CKD setting Cd and Hg as categorical variables. Logistic regression with restricted cubic spline was used to characterize a dose-response relationships between Cd or Hg concentrations and the risk of CKD in the study population.Results::The ORs for the risk of CKD comparing the fourth to the first quartile of blood Cd, blood Hg, urine Cd, and urine Hg were 1.77, 1.57, 2.03, and 1.50, respectively. Restricted cubic spline models showed that blood Cd and urine Hg were significantly linearly correlated with the risk of CKD, while blood Hg and urine Cd were non-linearly correlated with the risk of CKD with a steeper slope at concentrations <2.30 μg/L and 3.30 μg/g creatinine.Conclusions::Our findings suggest that even low Cd and Hg exposure (or non-industrial) were associated with increased risk of CKD in Chinese oldest old, although we did not find a significant multiplicative and additive interaction between Cd and Hg levels in relation to the risk of CKD.

Objective:To examine the association of blood uric acid (UA) and cognitive impairment (CI) among oldest-old adults in China.Methods:Data was collected in 9 longevity areas of China from Healthy Aging and Biomarkers Cohort Study (HABCS) conducted during 2017-2018. Finally,1, 622 elderly aged 80 years and older with complete information on blood UA and cognitive function score were included in this study. Information on demographic characteristics, lifestyle, and health status were collected through questionnaire and physical examination. Venous blood samples of the participants were collected to test blood UA level. Cognitive impairment (CI) was assessed using the Chinese Mini-Mental State Examination (MMSE) according to personal educational level. Generalized Estimating Equations (GEE) model for binary data was used to analyze the association of blood UA and CI, and further compared the associations among different age and body mass index (BMI) groups.Results:Of the 1 622 oldest-old, the mean age was (92.2±8.1) years, 656 (40.4%) were male, the mean level of blood UA was (343.3±86.2) μmol/L, and 482 (29.7%) oldest-old had CI. Compared with the lowest quartile of UA, the risks of CI in the second, third and highest quartiles were gradually reduced, the corresponding ORs and 95% CI were 0.99 (0.71-1.33), 0.87 (0.68-0.94) and 0.69 (0.48-0.85), respectively; and the linear trend test was statistically significant ( P<0.001). Subgroup analysis showed that the effects of higher UA associated with lower risk of CI were stronger in younger oldest-old (aged 80-89 years) and thinner group (BMI<24) ( Pinteraction<0.05). Conclusions:Blood UA was negatively associated with the risk of having CI in the oldest-old among the nine longevity areas of China.

Objective:To investigate the association of blood oxidative stress level with hypertriglyceridemia in the elderly aged 65 years and older in China.Methods:A total of 2 393 participants aged 65 years and older were recruited in 9 longevity areas from Heathy Aging and Biomarkers Cohort Study, during 2017 to 2018. Information on demographics characteristic, life style and health status were collected by questionnaire and physical examination, and venous blood was collected to detect the levels of blood oxidative stress and hypertriglyceridemia. The linear or non-linear association between oxidative stress and hypertriglyceridemia was described by restrictive cubic splines (RCS) fitting multiple linear regression model. The generalized linear mixed effect model was conducted to assess the association between oxidative stress and hypertriglyceridemia.Results:A total of 2 393 participants, mean age was 84.6 years, the youngest was 65 and the oldest was 112, the male was 47.9%(1 145/2 393), the triglyceride level was (1.4±0.8) mmol/L. The hypertriglyceridemia detection rate was 9.99%(239/2 393). The results of multiple linear regression model with restrictive cubic spline fitting showed that MDA level was linear association with triglyceride level; SOD level was nonlinear association with triglyceride level. MDA level had significantly association with hypertriglyceridemia, and the corresponding OR value was 1.063 (95% CI: 1.046,1.081) with 1 nmol/ml increment of blood MDA; SOD level had significantly association with hypertriglyceridemia, and the corresponding OR value was 0.986(95% CI: 0.983,0.989) with 1 U/ml increment of blood SOD. Conclusion:Among the elderly aged 65 and older in 9 longevity areas in China, MDA and SOD levels were associated with the risk of hypertriglyceridemia.

Objective:To investigate the association between oxygen saturation (SpO 2) and risk of 3-year all-cause mortality among Chinese older adults aged 65 or over. Methods:The participants were enrolled from Healthy Aging and Biomarkers Cohort Study in year of 2012 to 2014 in 9 longevity areas in China. In this prospective cohort study, 2 287 participants aged 65 or over were enrolled. Data on SpO 2 and body measurements were collected at baseline in 2012, and data on survival outcome and time of mortality were collected at the follow-up in 2014. Participants were divided into two groups according to whether SpO 2 was abnormal (SpO 2<94% was defined as abnormal). Results:The 2 287 participants were (86.5±12.2) years old, 1 006 were males (44.0%), and 315 (13.8%) were abnormal in SpO 2. During follow-up in 2014, 452 were died, 1 434 were survived, and 401 were lost to follow-up. The all-cause mortality rate was 19.8%, and the follow-up rate was 82.5%. The mortality rate of SpO 2 in normal group was 21.1%, and that of abnormal group was 41.6% ( P<0.001). After adjusting for confounding factors, compared to participants with normal SpO 2, participants with abnormal SpO 2 had increased risk of all-cause mortality with HR (95% CI) of 1.62 (1.31-2.02); HR (95 % CI) was 1.49 (0.98-2.26) for males and 1.71 (1.30-2.26) for females in abnormal SpO 2group, respectively; HR (95% CI) was 2.70 (0.98-7.44) for aged 65-79 years old, 1.22 (0.63-2.38) for aged 80-89 years old, and 1.72 (1.35-2.19) for aged over 90 years old in abnormal SpO 2 group, respectively. Conclusion:Abnormal SpO 2 was responsible for increased risk of 3-year all-cause mortality among Chinese elderly adults.

Objective:To investigate the relationship between the neutrophil-to-lymphocyte ratio (NLR) and the risk of depression symptoms among older adults aged 65 and above in 9 longevity areas of China.Methods:Data was collected in 9 longevity areas of China from Healthy Aging and Biomarkers Cohort Study (HABCS) conducted between 2017 and 2018. Finally,2018 elderly aged 65 years and above with complete information on neutrophil count, lymphocyte count and depressive symptoms were included in this study. Information on demographic characteristics, lifestyle, and health status was collected through questionnaire and physical examination. Complete blood counts which included lymphocytes and neutrophils were obtained by testing venous blood samples. Participants were divided into four groups by the quartile of NLR level, i.e. Q1, Q2, Q3, Q4. Logistic regression model was applied to analyze the association of NLR with depression symptoms. Results:Among 2 018 older adults, the mean(±SD) age was 82.6(±10.73), 1 032(51.14%) were male, 390(19.33%) were detected with depressive symptoms. Compared with participants of NLR in the 1 st quartile, the OR(95% CI) of risk for depressive symptoms was 1.47 (0.99, 2.19), 1.67 (1.13, 2.47) and 1.95 (1.32, 2.89), respectively. Conclusion:Increased NLR level is significantly related to depressive symptoms among elderly aged 65 years and above in 9 longevity areas in China.