The Short Physical Performance Battery (SPPB) is an objective tool for evaluating three domains  of lower extremity physical function in older age. It is unclear how the associations between SPPB scores and health outcomes persist over time. The aim of this 14-year cohort study was to investigate associations between SPPB scores and health outcomes among participants aged 60+ years in the English Longitudinal Study of Ageing (ELSA). The exposures were SPPB scores  at baseline (Wave 2). The outcomes were mobility impairments, difficulties in performing basic activities of daily living (ADL) or instrumental activities of daily living (IADL), and falls, measured at seven subsequent timepoints (Waves 3 to 9). The analyses involved linear and logistic multilevel regressions. After adjusting for potential confounders, a one-point increase in the total SPPB score was associated with a 0.13  decrease in mobility impairment, a 0.06  decrease in ADL disabilities, a 0.06  decrease in IADL disabilities, and 8%  lower odds of falling . Associations between the SPPB domains and health outcomes were more varied. The SPPB may be a useful measure for identifying older adults at a high risk of adverse outcomes. Biological aging in humans is often characterised by a decline in physical function including balance, muscular strength, and walking speed . Good phThe Short Physical Performance Battery (SPPB)  has emerIn addition to its widespread use as an outcome measure of physical function, previous work has shown that lower scores on the SPPB are associated with a range of adverse outcomes, including falls ,12, hospThe aim of the present study was therefore to examine associations of the SPPB and its domains of balance, strength, and gait speed with the key functional outcomes collected over 14 years. We hypothesised that higher total SPPB scores at baseline would be associated with more favourable outcomes over time, as would higher values across each of the domains.We used data from Waves 2 2004–2005) to 9 2018–2019) of the English Longitudinal Study of Ageing (ELSA) . Th. Th26]. ELSA has a hierarchical structure, with repeated measures nested within persons. Therefore, we included a random intercept at the individual level and a random slope according to time (defined by the wave of follow-up) in the linear multilevel models. Due to convergence issues encountered when running the random intercept and (random) slope models, random intercept (fixed slope) models were performed for all binary outcomes. The baseline cross-sectional sampling weight was applied to all models to improve population representativeness.As a sensitivity analysis, multiple imputation with chained equations was conducted to replace missing data on covariates and outcomes, using all exposures , outcomes, and covariates as predictors, as well as several baseline auxiliary variables including self-reported general health , occupational class , smoking status , alcohol consumption , living status , and the presence of any limiting long-standing illness (no versus yes). Predictive mean matching was used to impute the data on mobility impairment, ADL disabilities, IADL disabilities, BMI, and depressive symptoms, according to the “just another variable” approach . Followihttps://github.com/OliviaMalkowski/SPPB-study.git. Statistical significance was defined as p < 0.05.Multilevel models were performed using the “mixed” and “melogit” commands in Stata/BE Version 17.0 . The syntax is openly available at Of 6183 eligible participants aged 60+ years at baseline, our complete-case samples for models with mobility impairment, ADL or IADL disabilities, and falls as outcomes included 3548, 3547, and 3505 participants, respectively . Descripp < 0.001). The associations were non-linear (Model 3) in the models with ADL and IADL disabilities as outcomes (both p < 0.001). There was little change in the associations after adjusting for sociodemographic covariates (Model 4). The associations between the total SPPB score and mobility impairment ), ADL disabilities ), IADL disabilities ), and the odds of falling ) remained but were attenuated after further adjustment for health-related covariates (Model 5). The results were statistically significant  even when accounting for the baseline outcomes (Model 6). We found similar patterns of association when treating mobility impairment, ADL disabilities, and IADL disabilities as binary variables (In the univariate models (Model 1), a one-point increase in the total SPPB score was associated with a 0.55 decrease : −0.58, −0.52) in mobility impairment, a 0.16 decrease  in ADL disabilities, a 0.18 decrease  in IADL disabilities, and 15% lower odds  of falling on average across all follow-up waves . There wariables  and condariables .p > 0.05). For each one-point increase in the total SPPB score, the decrease in mobility impairment ) and the odds of falling ) was smaller among women than men, on average across all follow-ups (Model 8).There was a slightly greater decrease ) in IADL disabilities per one-point increase in the total SPPB score for older participants in our sample (Model 7). However, there was no evidence that the associations between the total SPPB score, and mobility impairment, ADL disabilities, or falls were modified by age , increased as follow-up progressed (Model 9). We found evidence of a non-linear influence of time (Model 10) on the association between the total SPPB score and mobility impairment . These interactions were statistically significant in the mutually adjusted models ), ADL disabilities ), and IADL disabilities ), but not falls (p = 0.005), the decrease in the odds of reporting one or more ADL disabilities for each one-point increase in the total SPPB score was smaller among older respondents ; Model 11) in the multilevel logistic model. The results of multiple imputation were comparable with the primary analyses. An exception was the interaction between the total SPPB score and time, which was no longer statistically significant (p = 0.079) in the model with mobility impairment as the outcome (Model 9). Moreover, there was evidence of an interaction between the total SPPB score and quadratic time ) on IADL disabilities (Models 10 and 11).No statistically significant interactions emerged in the multilevel logistic models with mobility impairment or IADL disabilities as outcomes. However, in addition to a statistically significant interaction with linear time (p ≤ 0.01), relative to individuals with zero points (the reference class). There was a clear gradient in ADL disabilities from the highest to the lowest balance score . Scoring three (odds ratio (OR) = 0.60, p = 0.042) or four  points on the balance test was associated with significantly lower odds of falling. Gait scores of two or more were associated with fewer mobility impairments and ADL disabilities, and lower odds of falling ; participants scoring three or four points on the gait test reported fewer IADL disabilities (both p < 0.001).In the unadjusted models Model 1; , balancep < 0.01). Three or four points on the gait test were associated with fewer mobility impairments (both p < 0.05), and four points were associated with fewer ) IADL disabilities. Higher gait scores were associated with significantly fewer ADL disabilities and decreased odds of falling . Sit-to-stand performance was associated with all outcomes in the expected directions in the unadjusted and fully adjusted models .In the fully adjusted models (Model 6), balance was not associated with mobility impairment. Only participants scoring four points on the balance test had significantly fewer IADL disabilities ) and reduced odds of falling ). Balance scores of two or more were associated with fewer ADL disabilities . Balance was not associated with mobility impairment or falls. Furthermore, only participants with gait scores of three or four had significantly fewer mobility impairments and lower odds of falling . In the fully adjusted models, balance and sit-to-stand scores were no longer associated with IADL disabilities or falls. A gait score of four was associated with a 0.70  decrease in mobility impairments and a 0.33  decrease in IADL disabilities. Participants scoring one, three, or four points on the gait test reported fewer ADL disabilities, and those scoring three or four points showed reduced odds of falling, relative to the reference groups . These patterns of the findings were broadly similar when using binary outcomes  possible score.The present study, importantly, provides evidence for the discriminant validity of the SPPB, that is, its ability to distinguish between people with high and low function, in line with their differing functional capabilities. The finding that the total SPPB score was associated with favourable outcomes is consistent with other studies that have explored associations between physical function and a range of physical health outcomes ,14,16,31An interesting finding of the present study relates to the incongruent results amongst the subcomponents of the SPPB tool. We hypothesised that each domain of balance, strength, and gait speed would be independently associated with the outcomes of interest. However, this was not entirely the case. Differences in the performance of the subcomponents may be explained by the way they assess the respective aspects of physical function. The measure of strength, which asks the participant to perform five sit-to-stand repetitions as fast as they can, is the only one of the three independent assessments to measure maximal capability. The balance task, by contrast, has three levels of difficulty but the test ceases if a participant holds each position for 10 s, with individuals being assigned maximum points for achieving all three. Indeed, a top score of 4 was by far the most frequent score amongst the analysed cohort, accounting for over 78% of participants. Similarly, the gait speed test, which asks participants to walk at their normal, rather than top, speed also does not require maximal effort. The frequency of achieving a top score for gait speed was 68% in the current sample, compared with 40% for the chair rise test.These findings suggest that the SPPB, when used as intended as a composite measure of physical function, is a useful tool for identifying individuals who might be more prone to falling or losing independence. Consistent with previous work, the analysis of this large dataset demonstrated that higher overall function scores may have a protective influence on physical health, both in the short and long term . The strA strength of the present work is the use of data from a large longitudinal cohort study with long-term follow-up that allows an assessment of the associations between physical function and physical health over time. This study also benefitted from a rigorous analysis of the SPPB and its domains using statistical models assembled in several stages. Still, the analysis may be limited somewhat by the homogenous sample in terms of ethnicity , self-reported outcomes that may be prone to bias, and survival bias within the study population as reflected by the observed attrition across timepoints, which, given the age of the population and the length of follow-up, was not unexpected. Moreover, while zero-inflated negative binomial models have been recommended for analysing count outcomes  with excess zeros, these models were not considered in the present work due to software constraints precluding the specification of a multilevel framework . NeverthOverall, this study demonstrated that the SPPB was associated with adverse future physical health outcomes in a sample of older adults in England. As hypothesised, we observed that higher overall physical function, as measured by the total SPPB score, was associated with the maintenance of mobility, retention of the ability to complete ADL and IADL, and lower odds of falling. While the SPPB-measured chair rise test appears to be a useful measure of lower extremity strength, for isolated assessments of balance or gait speed, researchers and practitioners may be advised to seek more robust and sensitive measures.


Coronary heart disease (CHD) is closely associated with cognitive impairment, especially in severe cases of heart failure. However, it is unclear whether cardiac systolic function plays a role in the relationship between pre-existing CHD and cognitive impairment in subjects without clinical heart failure.n = 118) and non-CHD (n = 90) groups according to the inclusion and exclusion criteria. The global cognitive function of all subjects was assessed by the Mini-Mental State Examination (MMSE) and cognitive impairment was defined as the score lower than the cutoff value. Left ventricular ejection fraction (LVEF) was measured using transthoracic echocardiograms. The relationship among pre-existing CHD, LVEF, and cognitive impairment was analyzed by multivariate logistic regression.In total, 208 subjects from the First Affiliated Hospital of Xi’an Jiaotong University were recruited from June 2014 to January 2015, and were divided into CHD (p = 0.011). Multivariate logistic analysis revealed that CHD was significantly associated with a higher risk of cognitive impairment  after adjusting for confounds except for LVEF. However, the OR of CHD decreased  when LVEF was further corrected as a continuous variable, and LVEF was negatively associated with the risk of cognitive impairment .In total, 34 subjects met the criteria of cognitive impairment. Univariate analysis showed that the cognitive impairment prevalence in the CHD group was significantly higher than that in the non-CHD group (22.0 vs. 8.9%, Pre-existing CHD is associated with a higher risk of cognitive impairment, and such an association can be considerably explained by reduced LVEF. An impaired cardiac systolic function may play a key role in the relationship between CHD and cognitive impairment among patients with pre-heart failure conditions. Coronary heart disease (CHD) and cognitive impairment are common diseases in older adults . The assPrevious studies have testified that cardiac systolic function parameters were associated with cerebral blood flow , brain vThis study aimed to research the relationship between pre-existing CHD and cognitive impairment in the subjects without clinical heart failure, and whether the association of them can be explained by reduced left ventricular ejection fraction (LVEF), the latter is widely applied to reflect the cardiac systolic function in clinical.12 deficiency; (5) carotid artery ultrasound examination revealed severe carotid artery stenosis (stenosis rate > 50%); and (6) other serious systematic diseases.This is a cross-sectional study to research the relationship among CHD, LVEF, and cognitive impairment. Subjects from the Department of Cardiology or Neurology, the First Affiliated Hospital of Xi’an Jiaotong University were recruited from June 2014 to January 2015. Inclusion criteria were as follows: (1) ≥50 years old; (2) for the CHD group: confirmed CHD history for more than 6 months, but no acute coronary event in last 6 months; for the non-CHD group: admitted to hospital because of increased blood pressure (BP), vertigo, or dizzy; (3) accepted the transthoracic echocardiograms; and (4) agreed to participate in the study and were able to finish the survey. The exclusion criteria were as follows: (1) subjects who suffered from other severe heart diseases, such as valvular heart disease, dilated cardiomyopathy, and severe arrhythmia ; (2) newly diagnosed acute coronary syndrome during hospitalization; (3) clinical heart failure, or the LVEF < 40%; (4) individuals who suffered from diabetes, stroke, Parkinson’s disease, intracranial space-occupying lesion, traumatic brain injury, epilepsies, uncorrected hypothyroidism, and vitamin BAll subjects accepted the general examination, such as electrocardiogram (ECG), cardiac enzymes, high sensitive cardiac Troponin I, ultrasonic cardiogram, and carotid artery ultrasonography; subjects with vertigo or dizziness accepted the imaging examination of the head (CT or MRI); and subjects with suspected acute coronary syndrome accepted coronary angiography.To start with, 252 subjects were enrolled in this study after being assessed for eligibility. Thereafter, those with one or more exclusion criteria were excluded. In total, 44 subjects were excluded and 208 subjects were left. Detail information was shown in All subjects passed a general cardiac examination after enrollment. For those with suspected CHD, CAG was also conducted. Cardiac physicians made the final diagnosis of CHD on the basis of the guidelines for cardiac disease . In thisTransthoracic echocardiograms were performed using the GE Vivid 7.0 ultrasound diagnostic instrument by trained echocardiographers from the Department of the Echocardiography, the First Affiliated Hospital of Xi’an Jiaotong University. LVEF was calculated with the Teichholtz formula to reflect the cardiac systolic function . The parGlobal cognitive function was assessed using the MMSE in a separate quiet room . CognitiThe demographic information, lifestyles, comorbidities, physical examination parameters, biochemical test parameters, and drug use before admission were collected. Most of the information collected is shown in p less than 0.05 was considered significant, and all tests were two sided. The characteristics of the subjects were reported as mean ± SD for normally distributed continuous variables, as the median (25 percentile and 75 percentile) for skewed continuous variables, and as numbers (percentages) for categorical variables. In univariate analysis, t-tests, rank tests, χ2 tests were performed according to the data types and distribution. In multivariate analysis, logistic regression models were performed to correct for confounding factors. In the logistic regression models, cognitive impairment (yes or no) was the dependent variable, and the CHD (yes or no) and confounding factors were independent variables.Statistical analysis was performed using SPSS 25.0 statistical software. A In multivariate analysis, we analyzed the relationship between cognitive impairment and CHD after correcting for most confounds collected in this study except LVEF (Model 1 and Model 2). In detail, age, gender, and years of education were corrected in Model 1. Lack of physical activities, tobacco use, alcohol consumption, hypertension, body mass index, triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, and homocysteine were further corrected in Model 2. Then, the LVEF was further corrected in Model 3 to analyze their correlation.In total, 208 subjects were included in this study, 118 subjects in the CHD group and 90 subjects in the non-CHD group. The mean age of the sample was 65.68 ± 8.76 years (range 50–86 years), and 117 (56.3%) of them were men. The MMSE score had a skewed distribution [27 ], and 34 subjects met the criterion of cognitive impairment. The LVEF value also showed a skewed distribution [66 ]. The detailed clinical information about the population was presented in p = 0.011)  . DetaileOR] = 3.425 , p = 0.009 and Model 2: OR = 3.284 , p = 0.044). The detailed information of the Model 1 and Model 2 have been described in the Statistical Analysis Section.Logistic regression models were established to correct the confounding factors. In the models, cognitive impairment (yes or no) was set as dependent variable, and the factors adjusted in different models are shown in OR of CHD in Model 3 decreased and the relationship between CHD and cognitive impairment was not so prominent as in Model 2 . Besides, LVEF was negatively associated with cognitive impairment , which indicated that the positive relationship between CHD and cognitive impairment could be considerably explained by the reduction of LVEF  was linked with an increased risk for the development of dementia and AD in the general population, and the result did not change even when all of the subjects with clinically prevalent cardiovascular disease were excluded . AnotherEpidemiology data suggested that cardiac dysfunction (mainly reflected by reduced cardiac output) was associated with smaller brain volumes  and whitThere are some strength in this study. First, participants are with relatively low diversity in the clinical manifestation and therapeutic management. The clinical characteristics of the CHD are diverse, with cardiac systolic function ranging from normal to advanced heart failure. The latter have been demonstrated as a risk factor of cognitive impairment. Besides, for those with acute myocardial infarction, the change of the cardiac systolic function may occur at once after myocardial infarction, but the effect of LVEF reduction on cognitive impairment may appear after a period of time because the change of cognitive function is a gradual process. The diversity in the subjects mentioned above may reduce the reliability of the result. Therefore, subjects with acute myocardial infarction, clinical heart failure or other severe heart diseases were all excluded in this study. Second, although subjects were recruited from hospital, the comparability between the CHD group and the non-CHD group was guaranteed by no significant difference of major confounding factors, especially the age and education. Third, our study found that the prominent relationship between pre-existing CHD and cognitive impairment can be considerably explained by a reduction in LVEF. Therefore, indicating that in clinical practice, cognition screening should also be considered in patients with CHD with reduced LVEF but not only with heart failure and early treatment to protect cardiac function may contribute to the maintenance of cognitive function. Last, for future relevant studies, LVEF is a necessary and important confounder, even in those without heart failure.However, some limitations also existed. First, we failed to define an exact cut-off value of LVEF that causes an increased risk of cognitive impairment because of the small sample size. Moreover, our study utilized a cross-sectional design, and the LVEF values were tested after admission, but the LVEF values of the subjects in the CHD group when they were diagnosed with CHD were seriously missing, and most of the subjects in the non-CHD group have not accepted the echocardiography examination before, so we could not assess the change courses of LVEF and their impact. Third, the subjects with CHD accepted different treatments, for instance, just medication or combined with vascular interventions. Recruiting more subjects and conducting subgroup analysis according to different treatments are necessary for future research. Finally, the correction for multiple comparisons was not performed, considering that this was an exploratory study with a small sample size. Therefore, “significant” results based on this exploratory study should be further verified in future confirmatory studies.Pre-existing CHD is positively associated with cognitive impairment, and this association can be considerably explained by reduction of LVEF. The cardiac systolic function may play a key role in the relationship between CHD and cognitive impairment.xm3215@126.com). After achieving ethical approval, requests for a de-identified dataset from this study may be sent to QQ, quqiumin@xjtufh.edu.cn.The datasets presented in this article are not readily available because the dataset contains patients’ other clinical information. Individuals interested in accessing the data must receive ethical approval from the Medical Ethics Committee of The First Affiliated Hospital of Xi’an Jiaotong University (The studies involving human participants were reviewed and approved by Medical Ethics Committee of The First Affiliated Hospital of Xi’an Jiaotong University. The patients/participants provided their written informed consent to participate in this study.QQ and SS designed this study. SS did the statistical analysis and co-wrote the manuscript. ZL took part in the survey, assisted with the statistical analysis, and co-wrote the manuscript. JG, JW, WL, YF, BZ, BM, PL, LM, YJ, CC, LD, and JL took part in the survey and collected the samples. QQ provided quality control and technical guidance in all stages of the study. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Several models have been developed to predict the risk of atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA). However, these models are of poor quality from the start. We, therefore, aimed to develop and validate a predictive model for post-operative recurrence of AF.In a study including 433 patients undergoing the first circumferential pulmonary vein isolation (CPVI) procedure, independent predictors of AF recurrence were retrospectively identified. Using the Cox regression of designated variables, a risk model was developed in a random sample of 70% of the patients (development cohort) and validated in the remaining  30%. The accuracy and discriminative power of the predictive models were evaluated in both cohorts.During the established 12 months follow-up, 134 patients (31%) recurred. Six variables were identified in the model including age, coronary artery disease (CAD), heart failure (HF), hypertension, transient ischemic attack (TIA) or cerebrovascular accident (CVA), and left atrial diameter (LAD). The model showed good discriminative power in the development cohort, with an AUC of 0.77 . Furthermore, the model shows good agreement between actual and predicted probabilities in the calibration curve. The above results were confirmed in the validation cohort. Meanwhile, decision curve analysis (DCA) for this model also demonstrates the advantages of clinical application.A simple risk model to predict AF recurrence after ablation was developed and validated, showing good discriminative power and calibration. Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice. As of 2019, there were approximately 59.7 million cases of AF  worldwide –5.Unfortunately, post-operative recurrence of catheter ablation (CA) of AF is relatively common. The recurrence rate of AF after CA based on circumferential pulmonary vein isolation (CPVI) is between 20 and 45% , 7. SuchExisting studies have shown that many risk factors are associated with the development of AF, including obesity, age, hypertension, and HF , 9. HoweIn previous studies, 12 models have been developed to predict AF recurrence, but their performance was disappointing . During This study was a retrospective cohort study. We consecutively included all patients who underwent RFCA of AF in Lanzhou University Second Hospital from April 2018 to August 2021. To our best knowledge, no previous studies have established a prediction model specific to paroxysmal atrial fibrillation (PAF). However, recent studies have confirmed that RFCA is safe and effective as the preferred treatment for symptomatic PAF, which provides a support for RFCA as the first-line treatment of PAF, and the recurrence rate of PAF patients after CA also lower , 18, 19.The study was approved by the Ethics Committee of the Second Hospital of Lanzhou University. All patients had signed the informed consent before RFCA. In addition, the study was approved for visa-free clinical trial informed consent. The study observed the 1964 Declaration of Helsinki and its later amendments.Preoperative 12-lead ECG and 24 h Holter monitoring were performed to evaluate the patient’s heart rhythm. Simultaneously, transthoracic and transoesophageal echocardiography were performed to evaluate the patient’s cardiac structure and to exclude left atrial thrombus. Besides, pulmonary vein CT and three-dimensional cardiac imaging were used to evaluate pulmonary vein and left atrial structure. Patients taking antiarrhythmic drugs (AADs) mainly including amiodarone and propafenone before RFCA should discontinue the drug for at least five half-lives.°C. During ablation of the posterior wall, the RFCA power was reduced to 25 W to reduce the risk of damaging surrounding structures. Whether to perform additional ablation  was up to the electrophysiologist. A fairly conservative strategy for additional ablations was followed. Cavotricuspid isthmus ablation was performed in patients with documented typical atrial flutter. The failure of pulmonary vein pacing to outward conduction can confirm efferent block, but it is necessary to avoid far-field capture of adjacent atrial tissue which lead to misjudgment. Observe 30 min after CPVI and verify the bidirectional block between the left atrium and pulmonary veins.All included patients with AF underwent ablation procedures based on CPVI. Intravenous fentanyl 1 ug/kg was administered at the beginning of the RFCA, followed by continuous fentanyl 1 ug/(kg/h) infusion. A decapolar catheter was placed from the patient’s right internal jugular vein to the coronary sinus. Then, the right femoral vein was punctured, and a septal sheath and a septal needle were inserted. If the right internal jugular vein fails or is anatomically abnormal, the right femoral vein may be selected. After successfully puncturing the interatrial septum, a 3.5 mm irrigated-tip ablation catheter was introduced, modeled under the guidance of CARTO3, for CPVI ablation with 30–40 W of energy and a set maximum temperature of 43The patient was free of bleeding within 5 h after CA and resumed oral anticoagulant use. Oral anticoagulants were maintained for 6 months, and after 6 months, the drug was discontinued or continued according to the CHA2DS2-VASc criteria. All patients with AF were treated with amiodarone  or propafenone , and AADs were discontinued after 3 months.The study endpoint was a late recurrence of AF, which could be symptomatic or asymptomatic, defined as any atrial arrhythmia  lasting more than 30 s between 3 and 12 months after RFCA. There were at least four outpatient follow-ups  after ablation, and 12-lead ECG and 24 h Holter monitoring were required for each follow-up. If they experienced symptoms of AF recurrence after the blank period to the end of the follow-up period, an ECG or electrocardiographic event recording should be performed immediately. When the patients did not follow up as planned, the patients were followed up by telephone. It should be emphasized that patients who still could not stop AADs after blank period were considered to have a AF recurrence.To avoid overfitting during model building, at least 10 events per variable were performed . Considet-test or the Mann–Whitney U test. Categorical variables were presented as frequencies (percentages), and differences between groups were compared using the χ2 test or Fisher’s exact test. The statistical significance level was set at a two-sided P < 0.05. Follow-up time was calculated from data received at the first RFCA until data reached the primary study endpoint. Univariate proportional-hazards Cox regression was used to identify predictors of post-operative AF recurrence in the development cohorts. Variables were evaluated, including age, gender, chronic obstructive pulmonary disease (COPD), coronary artery disease (CAD), hypertension, HF, hyperthyroidism, transient ischemic attack (TIA) or cerebrovascular accident (CVA), hyperlipidemia, hyperuricemia, diabetes, obstructive sleep apnea hypopnea syndrome (OSAHS), chronic kidney disease (CKD), LAD, and left ventricular ejection fraction (LVEF). It should be noted that HF is divided into heart failure with reduced ejection fraction (HFrEF), heart failure with mid-range ejection fraction (HFmEF), and heart failure with preserved ejection fraction (HFpEF), so LVEF was not included in univariate proportional-hazards Cox regression analysis. In univariate analysis, variables with p < 0.05 were included in the multivariate Cox regression model. Then stepwise regression is then performed based on the Akaike information criterion (AIC) to obtain the optimal model while preventing overfitting. 12 months survival nomogram was plotted based on the final multivariate Cox regression model.Continuous variables were expressed as mean ± standard deviation (SD) or median [interquartile range (IQR)], and statistical differences were estimated using the independent samples In development cohorts, the area under the curve (AUC) was used to evaluate the discriminative power of the survival nomogram. AUC > 0.7 indicates that the model has a high discriminative ability. A calibration curve was performed to assess the accuracy of the survival nomogram. The predictive ability of the newly built model and the C2HEST model is then compared using the Net Reclassification Index (NRI) and Integrated Discrimination Improvement (IDI). Besides, decision curve analysis (DCA) curves were drawn to assess the clinical benefit of the prognostic model . NomograP < 0.05). In addition, during the follow-up period, the number of patients who relapsed in development cohorts was 96 (31.5%), and in the validation cohort was 38 (29.7%), with no statistically significant difference between the two groups (p > 0.05).A total of 706 patients were included in the screening, and 433 were involved in the final analysis . BaselinPreoperative variables were performed to univariate Cox regression analysis. The analysis identified ten variables  highly associated with AF recurrence between 3 and 12 months after RFCA. Further, these 10 variables were included in a multivariate Cox regression analysis, and six independent variables  were obtained to predict the AF recurrence after RFCA . The resx-axis) matched the actual 12 months survival probability (y-axis).The model derived from development cohort was tested using internal validation. Similarly, in the validation cohort, the model also showed good predictive ability with an AUC of 0.77  . SimultaThe DCA of the model in development cohort  and valiP = 0.096), indicating that the new model did not significantly improve its predictive power compared to the standard model. In validation cohorts, similar results were observed. NRI and IDI were −0.089  and 0.002 (P = 0.418), respectively, with no statistical significance.In our previous study, we have confirmed that the C2HEST score, including CAD and COPD (each gets one point), H: hypertension (one point), E: elderly , S: systolic HF (two points), and T: thyroid disease , can be used to predict the AF recurrence after RFCA, and it has excellent discriminative power. In the development cohort, when the C2HEST score is used as the standard model, and the model established by development cohort is used as the new model, the calculated NRI  was 0.08This study developed a new model to predict the risk of late recurrence of AF after RFCA in development cohort. The model had good discriminative power with an AUC of 0.81 , and the calibration curve also suggested good agreement between predicted and actual probabilities. After further clinical DCA, it was found that predicting AF recurrence based on this model could lead to a net clinical benefit. In validation cohort, the performance of the model is similar to that in development cohort, further indicating that the model is stable while reducing the risk of overfitting.A recent meta-analysis summarized 33 studies on 13 models for predicting post-operative AF recurrence . UnfortuIn our newly developed model, the following risk factors were included: age, CAD, hypertension, HF, TIA or CVA, and LAD. Previous studies have shown that aging is a risk factor for AF, and the incidence of AF has been increasing with years. Elderly patients are often accompanied by various chronic diseases, the metabolic clearance capacity of AADs is reduced, and drug-related arrhythmias are more likely to occur. Besides, some studies suggest that the short-term success rate of CA for AF in elderly patients with indications (>75 years old) is comparable to that in younger patients, and there is no significant difference in the incidence of complications . The aboEpidemiological studies suggest that hypertension is the most crucial risk factor in patients with AF . If blooTIA or CVA often exists as a complication of AF. In addition, they are also risk factors for predicting the risk of stroke in patients with AF. There are few previous studies on TIA or CVA leading to post-operative AF recurrence. As far as we know, several studies have verified TIA or CVA as a risk factor for post-operative AF recurrence , 41. FurThe C2HEST model was initially used to evaluate the risk of AF in individuals. But many of its risk factors are related to the recurrence of AF, so it was innovatively used by us to evaluate the recurrence of AF after RFCA and was verified. However, the model was not initially used to evaluate the post-operative recurrence of AF, so there was a particular bias from the beginning. In addition, we also found that the population with paroxysmal AF has not been specifically studied in previous studies, but this is the main body of AF patients and the main population for the long-term benefit of RFCA . Finally, combined with previous post-operative recurrence prediction models for AF, the establishment is inferior . To address the above three problems, we conducted this study. Even though the model we built did not show better predictive ability than the C2HEST model, it is evident that the two models are different (including the purpose of building the model and the study subjects), so the clinical significance of the model cannot be denied.In our new model, all risk factors are available before RFCA, which means it can be used for preoperative guidance. The risk of recurrence in AF patients can be thoroughly evaluated before RFCA. That is to say, the risk of AF recurrence can be predicted based on the nomogram. Therefore, we can hypothesize that patients with a predicted recurrence risk of less than lower limit of recurrence rate in our center are the most suitable population for CA. For patients with a recurrence risk higher than upper limit of recurrence, CA is generally not recommended to avoid an unnecessary procedure. It should be noted that post-operative AF recurrence is definitely related to the type of AF and screening methods for recurrence , 44. DueThis study has several limitations. First, the study was single-center and could not be extrapolated to other centers. In addition, this study employed RFCA based on CPVI and, therefore, could not be easily generalized to other operation treatments. Second, the AF recurrence may be asymptomatic, so it is vital to strengthen the monitoring of heart rhythm. However, in our study, an implantable ECG event recorder was not used, so the AF recurrence rate may be underestimated to some extent. Third, and most importantly, we did not perform an external validation of the model, which could lead to an under-evaluation of the model. Obviously, to resolve the above problems, a multicenter, large sample study is needed to monitor patients after RFCA continuously.A new model was developed to predict the 12 months risk of AF recurrence after RFCA. The variables included in the model included age, CAD, hypertension, HF, TIA or CVA, and LAD. The model presents good discriminative power and calibration. In addition, the model demonstrated a net clinical benefit in DCA. Further, the above conclusion are confirmed in the verification cohorts.The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by the Ethics Committee of the Second Hospital of Lanzhou University. The ethics committee waived the requirement of written informed consent for participation. Written informed consent was not obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.GL completed the follow-up of patients, the data analysis, and wrote the manuscript. XG guided this clinical trial. J-JH and XW completed the manuscript revision. All authors listed have made a substantial, direct, and intellectual contribution to the work, and approved it for publication.


Contact dermatitis is a chronic inflammatory skin disorder with a highly variable prevalence worldwide. Smoking plays a crucial role in mediating inflammatory skin conditions such as contact dermatitis. The present study aimed to investigate the association between smoking status and contact dermatitis in the Saudi population. The patients in the present study were individuals older than 18 years who were diagnosed with contact dermatitis and received a patch test at the Department of Dermatology of King Saud University Medical City from March 2003 through February 2019. All patients were interviewed by phone to complete a specific pre-designed questionnaire to assess tobacco use or exposure history. The total number of enrolled patients in the study was 308 , all with contact dermatitis. Data from the present study suggest that the prevalence of allergic contact dermatitis in smokers may be less than that in non-smokers. Moreover, the prevalence of irritant contact dermatitis in smokers is more significant than in non-smokers. Finally, left-hand contact dermatitis is significantly associated with smoking. Therefore, there is a strong association between smoking and irritant contact dermatitis, especially in the Saudi population, regarding the left hand. Further epidemiologic studies are needed to further explore the role of smoking in the occurrence of contact dermatitis and to explore the possible mechanisms. Contact dermatitis (CD) is a chronic inflammatory skin disorder characterized by a skin reaction after exposure to an external agent . CD is fSeveral factors can trigger ACD and ICD, such as the type of irritant and allergen, duration of exposure, region, age, gender, race, occupation, and atopy . SmokingMultiple studies have focused on the possible pathogenic role of tobacco smoking in CD, and some studies have reported a relevant association ,17,18. HTherefore, the present study aimed to determine the association between smoking, ACD, and ICD; describe the general characteristics of smokers with contact dermatitis; and determine whether there is an association between the duration, frequency, or type of smoking with contact dermatitis. Additionally, we sought to identify whether there is an association between the location of CD and smoking among adults in Saudi Arabia.The present study was a retrospective cross-sectional study conducted among patients with CD. The study was conducted in accordance with the Declaration of Helsinki, followed the STROBE guidelines, and was approved by the Institutional Review Board of King Saud University College of Medicine IRB, Approval No. E-18-2858. Informed consent was obtained from all subjects involved in the study. Moreover, written informed consent has been obtained from the patients for publication. A patch test was performed on participants at the dermatology department of King Khaled University Hospital (KKUH), Riyadh, Saudi Arabia, from March 2003 through February 2019. The thin-layer rapid-use epicutaneous (TRUE) test unit contains panels 1.3 and 2.3 and includes 24 common allergens. The TRUE patch test is used in our dermatology department. In addition, patients were enrolled through the hospital’s dermatology database.All patients were interviewed by phone to complete a pre-designed questionnaire for assessing tobacco use or exposure history. All patients ≥ 18 years old, diagnosed with CD, and receiving a patch test were enrolled in the study and divided into two groups, ACD and ICD. The main criteria for ACD diagnosis were a positive patch test for relevant contact allergens, a direct relationship with allergen exposure or avoidance, and the spreading of skin lesions. A history of excessive contact with potential irritants, the temporal course of symptoms, and a negative patch test were the major criteria for diagnosing ICD. Patients with other skin diseases  were excluded from the study. The questionnaire was validated by expert academicians, who ensured that the questions effectively captured the topic under investigation. Based on the experts’ opinions, the tool’s content validity was estimated to be CVR = 0.63, CVI = 0.79. Since all questions had high CVR and high CVI, all questions were kept. The questionnaire’s reliability was calculated to be α = 0.95. The questionnaire was divided into four sections. The first section included demographic data, such as gender and educational level. The second section assessed the patient’s smoking status, including cigarette consumption and other related tobacco-containing products, and was based on a validated questionnaire  . The thip-value < 0.05 was considered statistically significant.The data were analyzed using the Statistical Package for Social Studies . The Chi-square test was used to analyze categorical variables, and Student’s t-test was used to assess continuous variables. Logistic regression was used to evaluate the risk factors. Continuous variables were expressed as mean ± standard deviation, and categorical variables were expressed as percentages. A Contact dermatitis is an inflammatory disease of the skin that is common in the general population. The pathophysiology of allergic contact dermatitis starts with the contact of the allergen with the skin . The patIn the present study, a total of 308  out of 350 patients agreed to participate in the current study, giving a response rate of 88%. Among them, 150 patients were diagnosed with ACD, and 158 were diagnosed with ICD. The total number of smokers was 31, and a significantly higher percentage of males were smokers than females . There was no statistically significant difference between smokers and non-smokers regarding age, educational level, dry skin, allergic rhinitis, and asthma. However, the previous parameters were higher in the non-smoker group .Moreover, the prevalence of ACD among smokers was 50% less than among non-smokers on average  = 0.5). On the other hand, smokers had a 50% higher prevalence (PR = 1.5) of ICD than non-smokers .After adjusting the data for age and gender using multivariable regression analysis, the effect of smoking on the prevalence of allergic contact allergy was not statistically significant .Furthermore, a higher percentage of patients with ICD were found to use cigarettes, cigars, and shisha compared with those with ACD, at 66.67%, 100.00%, and 66.67% vs. 33.33%, 0.00%, and 33.33%, respectively; however, the difference was only significant in the case of cigars .p = 0.369). These data are shown in In addition, the mean smoking duration of the current study’s smokers was 12.83 ± 9.55 years, and it was longer for ACD than ICD patients, at 20.25 ± 16.92 and 11.26 ± 6.99 years, respectively, but the difference did not reach statistical significance  affected more than one body area. For the single affected site, the hand was the highest in the two cases (ICD and ACD) and was not significantly higher in the smoker group, at 54 (19.5) vs. 9 (29), respectively. Moreover, there were no significant differences between smokers and non-smokers regarding the affected part of the body .p-value = 0.03)  in the smoker group compared to the non-smoker group  .The association between CD and smoking has not yet been established, especially in Saudi Arabia. However, Linneberg et al. reported a significant and positive dose-dependent relationship between smoking and CD, while a cross-sectional study of 520 participants found no association between smoking and nickel and cobalt sensitization ,17. The current study investigated the possible association between tobacco smoking and ACD and ICD. We found that ICD was more frequent among smokers. These results could be explained by the alteration in barrier function in tobacco smoking, allowing irritants and allergens to cross the barrier easily . MoreoveMoreover, two prospective population-based studies have suggested that tobacco smoking might decrease the risk of IgE-mediated diseases . In addiIn a review article addressing the association of smoking with contact dermatitis, seven out of eight articles described a positive relationship between smoking and ACD or ICD, and the authors concluded that smoking might be an essential risk factor for both ACD and ICD . AnotherSawada et al. reported that smoking increases the risk of hand eczema and contact dermatitis. Although the exact mechanism is still somewhat debatable, smoking boosts the Th1 immune response and IFN- cytokine production . PatientIt has been reported that tobacco and tobacco smoke are strongly associated with different skin conditions; among them, CD is of prime importance . CD ofteThe main limitation of the study was that the data were subjective, because they were collected through phone calls. The second limitation was that, due to the small sample size and because the study was only conducted in the Saudi Arabian population, it is not possible to draw generalized conclusions for other countries. Further studies are needed to confirm the relationship between smoking and dermatitis.The present study revealed that there is a strong association between smoking and irritant contact dermatitis. On the other hand, the study showed that smoking is inversely associated with allergic contact dermatitis. Additional epidemiologic studies are needed to further explore the role of smoking in the occurrence of contact dermatitis and to explore the possible mechanisms.


This study was to study the efficacy of rosuvastatin, amlodipine, and aspirin in the treatment of hypertension with coronary heart disease and its effect on platelet aggregation.  The participants included 60 patients with hypertension and coronary heart disease who were treated at our hospital between January 2020 and May 2021 and were randomly assigned to receive either rosuvastatin, amlodipine, and Ziyin Huoxue Recipe (observation group) or rosuvastatin, amlodipine, Ziyin Huoxue Recipe, and aspirin , with 30 patients in each. Outcome measures included clinical effectiveness, blood pressure indicators, blood lipid indices, plasma viscosity, platelet aggregation, cardiac function, and adverse responses. P < 0.05). The differences were found in blood pressure indices and blood lipid indices between the two groups before treatment (P > 0.05). However, after treatment, the blood pressure indices in the experimental group were significantly lower than those in the observation group (P < 0.05). After treatment, the blood lipid indices, plasma viscosity, and platelet aggregation in the experimental group were significantly lower than those in the observation group (P < 0.05). The left ventricular ejection fraction (LVEF) of patients in the experimental group after treatment was significantly higher than that of patients in the observation group (P < 0.05). There was no significant difference in the incidence of adverse reactions among patients in the two groups (P > 0.05).  The clinical efficacy in the experimental group was significantly higher than that in the observation group ( The clinical efficacy of rosuvastatin, amlodipine, and aspirin markedly reduces the blood pressure indices, blood lipid indices, plasma viscosity, and platelet aggregation of patients with hypertension and coronary heart disease, improves LVEF, and has a good safety profile. Hypertension with coronary heart disease is a common cardiovascular disease, with a high prevalence in the elderly . The cliAt present, given the absence of specific drugs for hypertension and coronary heart disease, its management is mainly performed empirically. Both hypertension and coronary heart disease damage vascular endothelial cells and increase platelet activity and blood viscosity, which aggravates illness in the coronary arteries . TreatmeRosuvastatin is a member of statins, which exerts their effects by blocking the HMG-CoA reductase enzyme in the liver. Studies have shown that rosuvastatin plays an important role in the treatment of hypercholesterolemia and hypertension . AmlodipPrevention of coronary heart disease is considered essential for the management of hypertensive patients. Aspirin is a nonsteroidal anti-inflammatory drug (NSAID) that is frequently used in the therapeutic setting. NSAIDs block the enzyme cyclooxygenase (COX) to provide analgesic, anti-inflammatory, antiplatelet, and antipyretic effects. Relevant investigations have validated the substantial antiplatelet effect of aspirin, and its involvement in the secondary prevention of coronary artery disease has received much clinical attention. . In tradhttp://www.randomizer.org/). For concealment of allocation, the randomization procedure and assignment were managed by an independent research assistant who was not involved in screening or evaluation of the participants.60 patients with hypertension and coronary heart disease treated in our hospital from January 2020 to May 2021 were recruited and randomly assigned to either the observation group or the experimental group, with 30 patients in each group. The randomization was carried out using an online web-based randomization tool  daily and 5 mg of amlodipine  dailyPatients in the experimental group additionally received aspirin. The patients received 300 mg of aspirin enteric-coated tablets  daily, and the dose was reduced to 100 mg daily after a month of treatmentTreatment efficacy: significantly effective: after treatment, the blood pressure was <140/90 mmHg, the pulse pressure was ≤50 mmHg, with a negative result on double 2-step ladder exercise testing and a normal electrocardiogram (EC G) at rest. Effective: after treatment, there was a decrease in systolic blood pressure (SBP) by less than 30 mmHg, a decrease in diastolic pressure (DBP) by less than 20 mmHg, and a pulse pressure between 50 and 100 mmHg, with a positive result on double 2-step ladder exercise testing and an improvement in the ECG at rest. Ineffective: after treatment, the blood pressure, the pulse pressure, result on double 2-step ladder exercise testing, and the resting ECG met the above stipulated criteriaThe blood pressure indices (SBP and DBP) of the two groups were measured using a sphygmomanometerBlood lipid indices: the BS-600 automatic blood biochemical analyzer (Shenzhen Mindray) was used to measure the level of total cholesterol (TC) and triacylglycerol (TG) of the two groups of patientsPlasma viscosity and platelet aggregation: an automatic blood analyzer was used to measure the plasma viscosity and platelet aggregation in all patients before and after treatmentCardiac function: Doppler ultrasound was used to measure the LVEF in patients before and after treatmentAdverse reactions: adverse reactions that may occur during treatment include dizziness, fatigue, nausea, and constipationb is unbiased and normally distributed. SPSS 22.0 software was used as the data analysis software. Measurement data were expressed as t-test. Count data were expressed as the number of cases (%) and analyzed using the X2 test. Statistical significance was indicated by P < 0.05. GraphPad Prism 8 was used to plot the graphics.If the parameter beta is either a difference of means, a log odds ratio, or a log hazard ratio, then it is reasonable to assume that P > 0.05) (The patient characteristics between the two groups were comparable ( > 0.05) .P < 0.05)  .P > 0.05). However, after treatment, patients in the experimental group had significantly lower blood pressure indices than those in the observation group (P < 0.05)  .P > 0.05). Patients in the experimental group exhibited considerably lower blood lipid indices following therapy than those in the control group (P < 0.05)  .P < 0.05)  .P > 0.05) (There was no significant difference in the incidence of adverse reactions between the two groups ( > 0.05) .In recent years, the incidence of hypertension has been increasing due to changes in diet and the development of bad habits. Ineffective control of blood pressure will lead to damage of blood vessels and various tissues and organs at all levels. Hypertension with coronary heart disease is one of the most common cardiovascular syndromes in clinical practice. It is considered a major cause of myocardial infarction and heart failure. Modern medicine shows that hypertension is an independent risk factor for the development of coronary heart disease, as it accelerates the progression of coronary atherosclerosis, leading to a rise in ventricular thickness and narrowing of coronary arteries. The hemodynamic changes produced by continuously increasing blood pressure activate platelets in the blood and contribute to atherosclerotic lesions, causing myocardial ischemia, hypoxia, or necrosis, resulting in coronary heart disease. Hypertension results in reduced blood preparation of coronary vessels, causing myocardial hypoxia and ischemia, and the incidence of coronary heart disease is considerably higher in patients with combined hypertension than in those without. Clinical research has gradually evolved from being focused on blood pressure reduction to treatment strategies that are aimed at reducing the comprehensive risk of hypertension .Ma  found thAmlodipine is a commonly used antihypertensive drug that reduces blood pressure mainly by inhibiting smooth muscle contraction, dilating peripheral blood vessels, and preventing endothelial injury . The medAspirin has remarkable antiplatelet activity and is considered effective in the prevention of thrombosis in patients with coronary heart disease .In the present, the findings revealed that clinical effectiveness in the experimental group was significantly better than that in the control group. This suggests that rosuvastatin, amlodipine, and aspirin outperform rosuvastatin and amlodipine alone, which may be attributed to the strong antiplatelet action of aspirin . In addiFurthermore, after treatment, the plasma viscosity and platelet aggregation of patients in the experimental group were considerably lower than those of patients in the observation group. It was also discovered that the LVEF of the experimental group after treatment was substantially greater than that of the observation group. This suggests that rosuvastatin, amlodipine, and aspirin are more effective than rosuvastatin and amlodipine alone in lowering plasma viscosity and platelet aggregation. And the results also found that there was no significant difference in the incidence of adverse reactions between the two groups, suggesting a high safety profile of rosuvastatin, amlodipine, and aspirin , 21.The treatment of coronary artery disease complicated with hypertension mainly focuses on vasodilatation to improve blood flow and lower blood pressure. Rosuvastatin calcium tablets reduce lipid deposition and delay the onset of atherosclerosis, amlodipine regulates blood pressure, and aspirin inhibits platelet aggregation, resulting in improved blood flow and reduced blood pressure. However, the cases in the present study were obtained from inpatients in the cardiovascular medicine department of our hospital, which is a single source and a small sample size, and the observation period is short, resulting in limitations in the clinical results. In addition, this study is a clinical study, which provides some references for future treatment and diagnosis. However, this study lacks animal tests to clarify what drug target the combination of these three drugs is based on, suggesting a lack of a more scientific basis. Future studies will further expand the source of cases and sample size, as well as design more indicators and extend the observation period and follow-up, so as to obtain more comprehensive data.The clinical efficacy of rosuvastatin, amlodipine, and aspirin markedly reduces the blood pressure indices, blood lipid indices, plasma viscosity, and platelet aggregation of patients with hypertension and coronary heart disease, improves LVEF, has a good safety profile.


Alzheimer’s disease (AD) and Lewy body dementia (LBD) are two different forms of dementia, but their pathology may involve the same cortical areas with overlapping cognitive manifestations. Nonetheless, the clinical phenotype is different due to the topography of the lesions driven by the different underlying molecular processes that arise apart from genetics, causing diverse neurodegeneration. Here, we define the commonalities and differences in the pathological processes of dementia in two kindred cases, a mother and a son, who developed classical AD and an aggressive form of AD/LBD, respectively, through a neuropathological, genetic (next-generation sequencing), and transcriptomic (RNA-seq) comparison of four different brain areas. A genetic analysis did not reveal any pathogenic variants in the principal AD/LBD-causative genes. RNA sequencing highlighted high transcriptional dysregulation within the substantia nigra in the AD/LBD case, while the AD case showed lower transcriptional dysregulation, with the parietal lobe being the most involved brain area. The hippocampus (the most degenerated area) and basal ganglia (lacking specific lesions) expressed the lowest level of dysregulation. Our data suggest that there is a link between transcriptional dysregulation and the amount of tissue damage accumulated across time, assessed through neuropathology. Moreover, we highlight that the molecular bases of AD and LBD follow very different pathways, which underlie their neuropathological signatures. Indeed, the transcriptome profiling through RNA sequencing may be an important tool in flanking the neuropathological analysis for a deeper understanding of AD and LBD pathogenesis. Alzheimer’s disease (AD) represents the major type of dementia worldwide , charactIt has long been known that AD and LBD pathologies are often coexisting , and AD/APP, PSEN1, and PSEN2, thanks to large GWAS and meta-analysis, up to 36 loci have been reported as possible contributors to AD [APOE gene remains the strongest genetic risk factor for AD [GBA, SNCA, and APOE [CNTN1, BCL7C/STX1B, and SCARB2, have been linked to LBD [AD and LBD also share similar genetics since variants in common genes have been described to date ,24,25,26rs to AD . Among tr for AD , increasand APOE ,30. Onlyd to LBD . Throughd to LBD ,32,33,34d to LBD . In thisAll clinical assessments were performed by the same team , according to the Abbiategrasso Brain Bank protocol (ABB) . The ABB2O2 in PBS for 10 min to neutralize endogenous peroxidase activity; only for some antibodies was a specific additional treatment necessary. To mask nonspecific adsorption sites, a preincubation with 5% normal goat serum was performed for 30 min, and then incubation with the primary antibodies overnight at room temperature followed. The following antibodies were used: 4G8, AT8, α-SYN (KM51), and phosphor-TDP-43 (pS409/410-2) to detect Aβ, pTAU, α-syn, and TDP-43 protein deposits, respectively  for annotation and variant prioritization, while the online VarSome tool , and bioinformatic processing was performed as reported previously . Produceune 2018 ) was usehttps://www.omim.org/; accessed on 14 June 2018), Decipher V9.29 , HSF , MGI , STRING , and GTEx  to assess their potential role in AD and LBD disease context. Final retained variants were validated using Sanger sequencing.The hereditary hypothesis analysis was performed, using the son as proband, to highlight both variants “in common”, thus present in both mother and son that may have contributed to the common clinical features, and variants “not in common”, thus present only in the proband and probably linked to the clinical signs manifested only by the son. Firstly, variants were retained according to the following criteria: (i) variants with minor allele frequency < 0.01 on the ExAC, GnomAD, dbSNP, and ESP6500 databases; (ii) variants that fall in the gene coding regions, splice site regions, and variants that disrupt the 3′/5′-untranslated regions; and (iii) variants with a read depth > 15. Variants retained were subsequently filtered according to patterns of inheritance . RetaineFrozen slices from four brain areas  of the two kindred cases and of the nondemented control were used to perform transcriptome analysis. Total RNA was isolated using Trizol® , and RNA quality and integrity were evaluated based on the RNA Integrity Number (RIN), acquired using the Agilent 2100 Bioanalyzer (Agilent RNA 6000 Nano Kit). RNA libraries were prepared in duplicate using the SENSE Total RNA-Seq Library Prep Kit  according to the manufacturer’s protocol. Libraries were sequenced using NextSeq 500 Sequencer . FastQ files generation and transcript mapping and quantification were performed as described in Zucca et al. 2019 . Differehttps://www.genome.jp/kegg/; accessed on 5 May 2019) pathway analysis were conducted via enrichR web tool [p-values < 0.05. Analyses were conducted by using all the DEGs (ALL_DEGs) and the separated upregulated (ALL_UP) and downregulated (ALL_DOWN) DEGs of each brain area of both mother and son. Only pathways and GO terms that were statistically significant were taken into consideration for further interpretations.Gene set enrichment analysis was performed for the differentially expressed coding genes (DEGs). Gene Ontology (GO) enrichment analysis for biological processes, cellular components, and molecular functions and a KEGG . The clinical history began at 78 years of age, with the development of a mild neurocognitive disorder (NCD) prevalent in memory and learning functions. Three years later, a progressive impairment of all cognitive domains leading to a diagnosis of dementia (major-NCD) arose. The patient died 12 years later, after typical, slowly progressive AD. Brain CT showed hippocampal and parietal atrophy. A cerebrospinal fluid (CSF) analysis was not performed. The clinical picture and course showed a slow but inexorable progression, scarcely influenced by drug therapies. At death, the CDR was 5 .Son (BB181). The son was a cultured and healthy man until the age of 68, when, a progressive cognitive impairment, especially in the memory and visuospatial areas, became evident. In less than one year, a condition of major-NCD was obvious. Brain MRI showed diffuse atrophy, and CSF analysis revealed a slight increase in total TAU (464 pg/mL) with phospho-TAU at the upper limit of the normal range (50 pg/mL) and Aβ peptide close to the lower limit (640 pg/mL). Due to memory and visuospatial deficits, his first diagnosis was probable AD with early posterior  involvement. The use of anticholinesterases resulted in a significant but transient improvement. Two years later, a frank parkinsonian syndrome with psychosis and fluctuations occurred raising the possibility of an LBD diagnosis. Due to the absence of relevant movement disorders and behavioral changes in the initial two years of the disease, a diagnosis of parkinsonism due to FTLD-TAU was ruled out. The patient was very sensitive to the action of neuroleptics; therefore, only quetiapine was administered to control the psychotic symptoms. The patient died of pneumonia one year later, only three years after the clinical onset. At death, the CDR was 3 (severe dementia). The final diagnosis was changed to probable mix dementia AD/LBD. Aside from his mother, he had no family history of dementia. His father died at a young age due to premature sudden cardiac death.Mother’s neuropathological picture confirms a definite AD diagnosis with high AD pathology, according to the ABC score . At the same time, it shows a mild to moderate presence of TDP-43 neuronal cytoplasmic inclusions in the amygdala and HiC and no α-syn deposits (2+) inactivation. Among the “not in common” (son-specific) variants, we found a heterozygous missense variant in the USP24 gene, classified as likely pathogenic according to the ACMG guidelines. Interestingly, USP24 falls in a locus (PARK10) significantly associated with PD [Focused exome gene panel was performed on the mother and son to screen the principal causative genes associated with AD, PD, and LBD. No pathogenic variants able to clearly explain the phenotype of the mother and the son were found. We further proceeded with the hereditary hypotheses analysis, merging the genetic data files of the two cases to create a common VCF with a total of 6734 genetic variants: 2461 present only in the mother, 2373 present only in the son, and 1900 present in both cases. Variants present in genes not associated with phenotypes similar to dementia or not involved in known pathways related to AD, PD, or LBD were discarded. Since no genetic information was available from the father, all variants present only in the son were considered de novo variants with respect to the mother genome. Hereditary hypotheses analysis highlighted six variants “in common” and six variants “not in common”, i.e., son-specific . Among t with PD . Both paWhole-transcriptome analysis of four different brain areas  was performed to detect the most dysregulated brain area in the two patients and the associated pathways involved after data normalization on the nondemented control. The brain areas with the highest number of DEGs resulted in the SN for the son with 2733 DEGs, followed by the PL for the mother with 351 DEGs . The HiCA principal component analysis (PCA) on all the DEGs derived from the two batches highlighted that the DEGs of the SN separate well for all the subjects from the DEGs of the other areas that instead overlap, except for the DEGs from one library replicate of the mother’s HiC, which was very different from all the other libraries and its replicate A. This dA KEGG pathway analysis for DEGs was performed according to Gagliardi et al. 2018 . For eacSon (BB181)  and more than 30 genes involved. Among the other pathways, we retrieved the “Nicotine addiction” pathway , which is related to the dopaminergic system, and the “Calcium signaling pathway”  , together with pathways involved in cancer. Other pathways were instead related to the cardiac system, such as the “Dilated cardiomyopathy”, the “Arrhythmogenic right ventricular cardiomyopathy”, and the “Hypertrophic cardiomyopathy” pathways  ( (BB181) . As expe 0.0025) A. Conver < 0.04) B. ConcerThe “Synaptic vesicle cycle” pathway, the most dysregulated pathway in the SN of the son, was further investigated . TranscrMother (BB105) (2+-dependent intracellular vesicle trafficking transcripts. (BB105) . GO term (BB105) . Specifi (BB105) . The GO Son (BB181) ( (BB181) . Top ten (BB181) . Associa (BB181) . Accordi (BB181) .Mother (BB105) ( (BB105) . PL was  (BB105) A. Howeve (BB105) B. In addMother and Son  of brain neurons, including Purkinje cells in the cerebellum, and other neurons in the cerebral cortex and the dentate gyrus of the HiC [2+ homeostasis is recognized as a central player in AD [2+ release is involved in vesicle fusion and neurotransmitter release [2+ homeostasis during the aging trajectory of the brain, contributing to the synaptic loss and the development of dementia. Very recently, it has been demonstrated that increased RyR2 open probability induces neuronal hyperactivity and memory loss, two common manifestations of AD and AD progression [Through NGS, we found no pathogenic variants in the causative genes known to be involved in AD and LBD. Through the hereditary hypotheses, we found common variants that may have triggered dementia in both individuals and variants present only in the son that may be responsible for the parkinsonian spectrum and the LTS. Among the common variants present in both cases, the only one classified as pathogenic by the ACMG guidelines was a disruptive in-frame insertion (c.12948_12950dupAAG) in the RYR2 gene, which codifies for the Ryanodine Receptor Type 2 (RyR-2). RyR-2 is a Ca the HiC ,52. Perter in AD ,54 and i release . This evgression . Moreovegression . Among tgression . The vargression . Moreovegression ,61. Alth2+ signaling” pathways. While both pathways have been already reported in association with PD [Through RNA-seq of four selected brain areas  of the two cases and the control case, we identified the most dysregulated brain areas of the two subjects, the SN in the son and the PL in the mother. Specifically, the SN of the son was found to be the brain area with the highest number of DEGs compared to all the other brain areas analyzed either in the subject and in the mother. Downregulated genes in this area were related to the synaptic signaling, mainly to the dopaminergic and the GABAergic synapses. Among the retrieved DEGs, TH, SLC6A3, and SLC18A2 were the genes with the largest differences in expression between the patient and the nondemented control, and all three were highly downregulated. TH codifies for tyrosine hydroxylase, which is involved in the conversion of tyrosine to dopamine in the dopaminergic neurons; SLC18A2 is involved in the loading of dopamine in the presynaptic vesicle for its release, and SLC6A3 codifies for the dopamine transporter (DAT), which is involved in the reuptake of dopamine in the presynaptic terminals. The downregulation of these three genes in the SN of the son may reflect the loss of dopaminergic neurons in the SN pars compacta, showing that the transcriptomic analysis strictly correlates with the neuropathological examination and may become a useful supportive tool in flanking challenging diagnoses. On the opposite side, among the most upregulated pathways in the son’s SN, we found the “Synaptic vesicle cycle” and the “Ca with PD ,63,64, nUnlike the son, the transcriptome analysis of the mother revealed that the PL was the most dysregulated brain area, according to the neuropathology, which showed an abundance of TAU deposition precisely in the PL. The parietal lobe is gaining even more attention in the development of AD ,66,67. PThe other two brain areas, the HiC and the BG, were less dysregulated compared to the SN and the PL. Particularly, mother and son were similarly dysregulated within the BG according to their pathology, which was quite similar in this area and characterized by moderate amyloid deposition. It is noteworthy that in both cases the BG were not affected by specific proteinopathies (TAU/synuclein) but only by diffuse amyloid plaques, with little impact on the transcriptome. Conversely, the HiC was early affected by the disease and was an area with severe degeneration in both subjects, with double proteinopathy (TAU/synuclein) in the son. Nonetheless, this area appeared slightly dysregulated. Our data let us hypothesize that the amount of transcriptional dysregulation may be related to the level of damage accumulated across time by the different brain areas. The HiC, which was the first and most damaged brain area in both mother and son with the majority of dying or critically damaged cells, became less prone to respond to tissue damage through transcriptional dysregulation, reducing the transcriptional machinery’s ability to work at basal levels due to cell dysfunction or, possibly, with the aim to preserve at most cell survival. Brain areas with modest or late involvement of pathological changes, as in the case of the BG of the two cases, started to overcome tissue damage, resulting in a low and similar level of dysregulation. Lastly, areas affected by an evolving active pathology were highly and specifically dysregulated, as in the case of the SN and the PL in this study. They are still transcriptionally active and result in a peculiar transcriptional dysregulation depending upon the underlying pathogenesis and influencing the type of pathology. This work shows that the alterations of the transcriptome might follow the pathology according to a temporal and topographical trajectory where the less affected areas and, paradoxically, the most affected ones appear to be the least dysregulated, while areas with greater dysregulation are those in which the pathology is more active. Eventually, the interaction between genomics and transcriptomics may be crucial for identifying disease pathways and creating precise, powerful medications. Indeed, the identification of risk variants and disease-specific pathways, together with the possibility to follow brain changes throughout the disease by following the transcriptional dysregulation of different brain areas, might become helpful for the development of therapeutic strategies that target molecular pathways involved in AD and/or LBD, where effective treatments are still missing.To our knowledge, this is the first study that compares the transcriptomic profile of different brain areas in kindred cases affected by different types of dementia, specifically AD and LBD. Here, we highlighted that the LBD pathology, compared to the AD, undergoes higher transcriptional dysregulation, especially within the SN, while in the AD context, a lower degree of transcriptional dysregulation was found, with the PL being the most involved brain area. In particular, we found a link between the level of transcriptional dysregulation in the different brain areas and the level of tissue damage accumulated across time. Even if AD and LBD may have a clinical overlap, our data highlight that the molecular bases of AD and LBD may follow very different pathways, and that transcriptome profiling through RNA sequencing may be an important tool in flanking the neuropathological examination for the differential diagnosis and for elucidating neuropathogenesis of AD and LBD.


Physical activity is needed in today’s highly sedentary society. Research into Chinese trends with respect to the longitudinal association between changes in physical activity (PA) and dyslipidemia (DL) is limited. The present study assessed PA and PA-related changes associated with the level of serum lipids, and the risk of dyslipidemia stratified by gender, via a population-based longitudinal observational study among adults (>18 years old) residing in nine provinces in China. Data of 3380 adult participants, gleaned from two surveys in 2009 and 2015 used by the China Health and Nutrition Survey (CHNS), were analyzed. Three-level random intercept growth models were used to calculate the associations between total physical activity (TPA), the four activity subtypes, and changes in the level of blood lipids. Three-level logistic regression models were utilized to assess the association between TPA and the risk of DL. The highest level of TPA was observed to correlate with the lowest prevalence of DL. Compared with the lowest level of TPA, the highest level of TPA increases the concentration of HDL-C  in males, and also reduces the risk in males of having low HDL-C by 31% . Occupational PA was positively associated with higher HDL-C levels in both genders , and leisure-time physical activity (LTPA) was negatively associated with TG levels in males. Increasing TPA benefited HDL-C levels in males, irrespective of the level of basic TPA of individuals. Physical activity  was superior in positively influencing HDL-C in males, but not in females. Leisure-time physical activity needs to be increased substantially in order to increase TPA to levels that would be beneficial to blood lipid levels and DL, irrespective of baseline TPA levels. Dyslipidemia (DL), which is characterized by high low-density lipoprotein cholesterol (LDL-C), low high-density lipoprotein cholesterol (HDL-C), high total cholesterol (TC), and high triglycerides (TG), has emerged as the second leading factor associated with the risk of cardiovascular disease (CVD), and has been reported to have caused an increase in the annual total mortality directly related to dyslipidemia in China from 2.51 million in 1990 to 3.97 million in 2016 ; in contPhysical activity (PA) refers to all movement, and is classed into four types, including occupational PA, travel PA, domestic PA, and leisure-time PA (LTPA), and has been shown to contribute to the prevention and management of CVD . TogethePrevious studies have suggested that exercise has beneficial effects on serum lipid metabolism in healthy individuals and also in those with chronic illnesses . No mattIn addition, there are other limitations that have not been addressed in previous studies. For example, both Chinese and international studies have reported the significant negative association between exercise or LTPA, and deranged blood lipids and the risk of DL ,16,17,18To address these knowledge gaps, data from Chinese adults (age ≥ 18 years) obtained in 2009 and 2015 from the China Health and Nutrition Survey (CHNS) were used to examine the association between PA, the subgroups of PA, changes in PA, and serum lipids, stratified by gender. We also aimed to assess the effect of TPA on the risk of DL.https://www.cpc.unc.edu/projects/china (accessed on 9 January 2023), and elsewhere [The CHNS is an ongoing multipurpose large-scale longitudinal survey, with the aim of capturing sociological, economic, and demographic factors that influence health and nutritional status across the Chinese life span. Initiated in 1989, China has seen a total of 11 CHNS surveys  being conducted thus far. The original survey used a multistage, random cluster design in eight provinces, using a weighted sampling method to select a stratified probability sample. Specific individuals participated in the survey repeatedly at each round unless they were lost to follow-up. Further details regarding the CHNS are described and can be accessed at the following internet website: n = 1990) or TPA (n = 14) were deleted. After excluding participants that were associated with myocardial infarction, stroke, cancer, fracture, asthma, or taking blood pressure medication (n = 668), and those associated with either extreme daily energy intake  (n = 261), those with extreme BMI , and those with extreme TPA , n = 3), a total of 3380 participants (6760 observations) were included in the final analysis . The number of participants (age ≥ 18 years) recorded in the two surveys who were not disabled, not pregnant, and not lactating was 6413. Participants that omitted data on blood lipid profiles , and the Institutional Review Committee of the University of North Carolina at Chapel Hill, and written informed consent was obtained from all the CHNS participants before data collection.We relied on a standard PA questionnaire  to calcThe relationship between TPA and certain specific lipid changes seen after 6 years was observed to be statistically significant. In order to describe the association between this interaction and the serum lipids, we categorized TPA into low, moderate, and vigorous activity, according to tertiles in 2009. The change in value was defined as the TPA in 2015 minus the TPA in 2009. This result was not normally distributed, with no significant difference between males and females. Therefore, we stratified the TPA change value into tertiles, which were ‘decreased’ (−267.64~−31.22 MET MET·h/week), ‘stable’ (−31.19~0.41 MET MET·h/week), and ‘increased’ (0.46~259.00 MET·h/week). There were thus nine categories defining the basic TPA × change value, which included: vigorous and increased, vigorous and stable, vigorous and decreased, moderate and increased, moderate and stable, moderate and decreased, low and increased, low and stable, and low and decreased. Based on our data, the low and decreased group was not represented; we thus used the data of the other eight groups, and the last group was used as a reference group.Sedentary behaviors were calculated as the average hours per day (hour/day) spent in various non-occupational recreational activities, including lying down, sitting , and watching TV or movies/videos. A summation of the time spent engaged in these activities was used to obtain the total time expenditure on sedentary behaviors, which was not included in the PA calculation.Trained health workers or nurses measured the weight, height, and waist circumference of participants, following standardized procedures. Height and weight were measured based on a standard protocol. Weight in lightweight clothing was measured to the nearest 0.1 kg, with the participant standing without shoes, and height was measured without shoes to the nearest 0.1 cm using Seca 206 wall-mounted metal tapes. We calculated BMI as weight in kg divided by height in square meters. Waist circumference was measured in centimeters at the mid-point between the lowest rib margin and the top of the iliac crest during light breathing using a Seca tape measure.Overnight fasting blood was collected from the antecubital vein of participants in the morning. Plasma and serum samples were processed  within two hours of collection in local hospitals. The aliquots were frozen and stored at −86 degrees centigrade for later laboratory analysis. All samples were analyzed in a national laboratory in Beijing with strict quality control. Serum TG, TC, HDL-C, and LDL-C were measured via the CHOD-PAP  method.According to the 2016 Chinese Adult Dyslipidemia Prevention Guideline, the definition of DL is a TC ≥ 6.2 mmol/L (240 mg/dL) and/or a TG ≥ 2.3 mmol/L (200 mg/dL) and/or a HDL-C < 1.0 mmol/L (40 mg/dL) and/or a LDL-C ≥ 4.1 mmol/L (160 mg/dL). Four clinical subtypes of DL were identified. Hypercholesterolemia was defined as an isolated presence of a TC ≥ 6.2 mmol/L (240 mg/dL). Hypertriglyceridemia was defined as the isolated presence of TG ≥ 2.3 mmol/L (200 mg/dL). Combined hyperlipidemia was a combination of both hypercholesterolemia and hypertriglyceridemia. Low HDL-C was defined as the isolated presence of a HDL-C of <1.0 mmol/L (40 mg/dL).Well-trained interviewers used standard questionnaires to collect sociodemographic data, including annual per capita household income, current smoking status, alcohol consumption, community information (urbanization index), and dietary intake. Educational level was divided into two categories, i.e., less than high school education and high school education and above. We defined marital status as “married” and “not married”. Participants reported their gross annual per capita household income according to household size, and their 2009 gross annual income was inflated to year 2015 equivalency. The community urbanization index, which was standardized and validated, captured the changes in 12 multidimensional components at the community level reflecting population density, economic activity, traditional markets, modern markets, transportation infrastructure, sanitation, communications, housing, education, diversity, health infrastructure, and social services ,24. We cWe calculated descriptive statistics for the individual demographic variables in 2009 and stratified them by gender. The median and the 25th and 75th percentiles were used to express continuous variables because of their abnormal distribution. Categorical variables were expressed as percentages. Kruskal–Wallis tests were used for continuous variables and Chi-square tests were conducted for categorical variables. Prevalence was defined as the ratio of all patients with DL for all participants in that year.Unlike hypertension and diabetes, and apart from medication, DL as the dependent variable seemed to be more amenable to modification by diet and lifestyle improvement. A participant with DL is more likely to have normal blood lipids at the next survey round in the absence of medication if diet and lifestyle changes have been implemented. Similarly, TPA, as an independent variable, was utilized as the fixed variable in the statistical models in previous studies, because it was assumed that TPA was fixed. However, TPA should be treated as a volatile variable because it is easily changed as age increases and personal willingness to perform physical activities declines. Therefore, the multi-level random intercept growth model is more suitable for longitudinal data analysis than is the COX proportional hazards regression model because the latter model assumes that all variables are fixed.p < 0.01).Because of the nested data structure, the association between PA and blood lipids (or DL) may be presented as multiple-level relationships. HDL-C levels, LDL-C levels, TC levels, TG levels, and DL were our dependent variables. We tested the contribution made by the community level (third level), the individual level (second level), and the residual level (first level). The community level was found to contribute 5.18%, 7.06%, 6.92%, 3.70%, and 4.84% to HDL-C levels, LDL-C levels, TC levels, TG levels, and DL, respectively. All second level and third level contributions were calculated to be statistically significant  was the reference level.Additionally, for the four subtypes of PA, three-level random intercept growth models were constructed, which were adjusted for survey round, baseline age, energy intake, energy from dietary fat, dietary cholesterol, BMI, waist circumference, whether a current smoker, whether an alcohol consumer, education, per capita household income, sedentary activity time, and the urbanization index. We also used the three-level random intercept growth models to test the association between the baseline TPA level and its changing type within the six years under consideration (2009–2015) and blood lipids, adjusting for survey round, baseline age, energy intake, energy from dietary fat, dietary cholesterol, BMI, waist circumference, whether a current smoker, whether an alcohol consumer, and sedentary activity time.p-values were two-sided and a p-value of <0.05 was considered to be statistically significant.All statistical tests and scatter diagrams were conducted using SAS software . The three-level random intercept growth model used the PROC MIXED process and the three-level logistic regression model used the PROC GLIMMIX process. All the continuous variables were centrally processed using , if the level of PA is high enough. Additionally, occupational PA contributes to higher HDL-C levels, and increasing TPA is beneficial to HDL-C levels in males, no matter what the individual basic level of TPA is. This succinctly explains the association between daily TPA and blood lipids among Chinese adults and contributes to contemporary knowledge related to the precise PA recommendations for each DL subgroup.The overall prevalence of DL increased from 32.54% to 40.53% between 2009 and 2015  and was Even so, we observed participants with the highest TPA level enjoying the lowest prevalence of DL  and the High concentrations of serum LDL-C increase the risk of cardiovascular complications. However, HDL-C transports lipids back to the liver for circulation and processing, and thus is protective to the cardiovascular system . Althouge TG levels; however, this association is weaker after adjustment for HDL-C levels, and fully compensated for after correction for non-HDL-C [Triglycerides are measured as part of the routine lipid profile; however, the relationship of TGs to CVD risk has been controversial in the past, and has been overshadowed now by the role of HDL-C . Epidemion-HDL-C . Our datOur study showed that TPA and the four PA subtypes underwent a dramatic decrease within the six years between 2009 and 2015; even so, occupational PA accounted for the biggest fraction of PA at all times, and LTPA accounted for the smallest fraction of PA, and was calculated to be less than 10% . SpecifiOur study shows that a vigorous basic TPA level results in improved HDL-C for men, and that the degree of HDL-C elevation positively correlates with the increase in TPA, no matter what the basic TPA level is in males. The regression coefficient of HDL-C gradually increased in ‘low’, ‘moderate’, and ‘vigorous’ order. At the same basic TPA level, the regression coefficient of HDL-C gradually reduced from ‘increased’, to ‘stable’, and then to ‘decreased’. In one prospective study of 1860 Swedish men, Byberg  observedAdjustment factors at the time level, the individual level, and the community level were considered in the multilevel models. There are few studies covering as many confounding factors as ours. Body mass index and waist circumference were independently and positively associated with the risk of DL ,47. EnerOur study extends contemporary knowledge in several important ways. First, our study is one of the largest and most recent studies to show the nationwide characteristics of longitudinal TPA and DL trends in China. Our strict quality control ensured accurate results, which allowed the ability to make certain generalizations. Although the prevalence of DL was consistent with previous studies and meta-analyses, the longitudinal data allowed us to draw robust conclusions with respect to causal relationships. This is the first study discussing the association between TPA, activity subtypes and their change, and DL in China. Studies concerning specific subtypes of PA associated with diseases should be conducted in the future. In addition, to analyze the association between PA and DL, we adjusted for as many confounders as possible, including social demographic characteristics, diet, physical measurements, and urbanization variables, and the estimated values were reasonable and strictly controlled.Some limitations of this study should be considered. Physical activity was derived from a questionnaire, which may lead to recall bias. However, the questionnaire was broadly acceptable to participants, and was the most economical and useful method to employ for a large-scale survey across nine Chinese provinces. In this 30-year large scale follow-up survey, it is impractical to obtain objective measures of usual activity levels using an accelerometer. The interviewer-administered PA questionnaire concerning frequency, duration, and intensity of PA within 1 week in several different domains has been tested, modified, and used since 1989, and has been derived from the internationally used PA questionnaire. It has been consistently used in each round of the CHNS. Family history and the disease history of DL and medications used were not specially considered and included in the standard questionnaire. To a certain extent, this might cause bias. Third, we excluded a large proportion of the participants from our analysis for varying reasons, and the remaining analytical sample was relatively smaller, thus implying that the generalization of our results to the entire survey population should only be made with caution.Further study in this area of interest should encompass additional cycles of longitudinal data, and should reveal the PA trajectory for China, and may also reveal more robust associations between the PA trajectory and blood lipids in the Chinese population.The findings from the present study indicate that the highest level of TPA is associated with the lowest prevalence of DL. Physical activity is superior in improving blood lipids in males, but not in females. The highest level of TPA is effective in improving the concentration of HDL-C and controlling the risk of low HDL-C in men. Occupational PA contributes to higher HDL-C levels and increasing TPA is beneficial to HDL-C levels in males, even in those with a basic low TPA level. Movement is much more desirable than being sedentary, and LTPA in ordinary people should ideally be raised substantially to improve TPA levels as much as possible in order to be of benefit to prevailing blood lipid levels and DL.