BACKGROUND: The American Heart Association (AHA) introduced the concept of cardiovascular-kidney-metabolic (CKM) health and stage, reflecting the interaction among metabolism, chronic kidney disease (CKD), and the cardiovascular system. However, the association between CKM stage and the long-term risk of cardiovascular disease (CVD) has not been validated. This study aimed to evaluate the long-term CVD risk associated with CKM health metrics and CKM stage using data from a population-based cohort study. METHODS: In total, 5293 CVD-free participants were followed up to around 13 years in the Chinese Multi-provincial Cohort Study (CMCS). Considering the pathophysiologic progression of CKM health metrics abnormalities (comprising obesity, central adiposity, prediabetes, diabetes, hypertriglyceridemia, CKD, and metabolic syndrome), participants were divided into CKM stages 0, 1, and 2. The time-dependent Cox regression models were used to estimate the cardiovascular risk associated with CKM health metrics and stage. Additionally, broader CVD outcomes were examined, with a specific assessment of the impact of stage 3 in 2581 participants from the CMCS-Beijing subcohort. RESULTS: Among participants, 91.2% (4825/5293) had at least one abnormal CKM health metric, 8.8% (468/5293), 13.3% (704/5293), and 77.9% (4121/5293) were in CKM stages 0, 1, and 2, respectively; and 710 incident CVD cases occurred during a median follow-up time of 13.3 years (interquartile range: 12.1 to 13.6 years). Participants with each poor CKM health metric exhibited significantly higher CVD risk. Compared with stage 0, the hazard ratio (HR) (95% confidence interval [CI]) for CVD incidence was 1.31 (0.84-2.04) in stage 1 and 2.27 (1.57-3.28) in stage 2. Significant interactive impacts existed between CKM stage and age or sex, with higher CVD risk related to increased CKM stages in participants aged <60 years or females. CONCLUSION These findings highlight the contribution of CKM health metrics and CKM stage to the long-term risk of CVD, suggesting the importance of multi-component recognition and management of poor CKM health in CVD prevention.
Humans ; Female ; Male ; Cardiovascular Diseases/etiology* ; Middle Aged ; Adult ; Cohort Studies ; Renal Insufficiency, Chronic/metabolism* ; Aged ; Risk Factors ; Metabolic Syndrome/metabolism* ; China ; East Asian People

Background::Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China.Methods::Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed.Results::A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43–0.68; P <0.001). At discharge, the prescription rate of OAC was 45.2% (16,757/37,087) in eligible patients with high stroke risk and 60.7% (2778/4578) in eligible patients with low stroke risk. OAC utilization in patients with high stroke risk on admission or at discharge both increased largely over time (all P <0.001). Multivariate analysis showed that OAC utilization at discharge was positively associated with in-hospital rhythm control strategies, including catheter ablation (adjusted odds ratio [OR] 11.63, 95% confidence interval [CI] 10.04–13.47; P <0.001), electronic cardioversion (adjusted OR 2.41, 95% CI 1.65–3.51; P <0.001), and anti-arrhythmic drug use (adjusted OR 1.45, 95% CI 1.38–1.53; P <0.001). Conclusions::In hospitals participated in the CCC-AF project, >70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration::ClinicalTrials.gov, NCT02309398.

Objective:To explore the clinical, biochemical and genetic characteristics of three children with Isoleucine metabolic disorders due to variants of HSD17B10 and ACAT1 genes. Methods:Two children with 17β hydroxysteroid dehydrogenase 10 (HSD17B10) deficiency and a child with β-ketothiolase deficiency (BKD) diagnosed at Shanghai Children′s Hospital between 2014 and 2021 were selected as the study subjects. Clinical data of the children were collected. The children were subjected to blood acylcarnitine, urinary organic acid and genetic testing, and candidate variants were analyzed with bioinformatic tools.Results:The main symptoms of the three children had included epilepsy, developmental delay, hypotonia and acidosis. Their blood acylcarnitine methylcrotonyl carnitine (C5: 1), 3-hydroxyisovalerylcarnitine (C5-OH) and 3-hydroxybutylcarnitine (C4OH) were increased to various extents, and urine organic acids including methyl crotonylglycine and 2-methyl-3-hydroxybutyric acid were significantly increased. Child 1 and child 2 were respectively found to harbor a c. 347G>A (p.R116Q) variant and a c. 274G>A (p.A92T) variant of the HSD17B10 gene, and child 3 was found to harbor compound heterozygous variants of the ACAT1 gene, namely c. 547G>A (p.G183R) and a c. 331G>C (p.A111P). Among these, the c. 274G>A (p.A92T) and c. 331G>C (p.A111P) variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively classified as variant of unknown significance (PP3_Strong+ PM2_supporting) and likely pathogenic (PM3+ PM2_Supporting+ PP3_Moderate+ PP4). Conclusion:Both the HSD17B10 deficiency and BKD can lead to Isoleucine metabolism disorders, which may be difficult to distinguish clinically. Genetic testing can further confirm the diagnosis. Discoveries of the HSD17B10: c. 274G>A (p.A92T) variant and the ACAT1: c. 331G>C (p.A111P) variant have enriched the mutational spectrum of the two diseases.

AIM: To explore the molecular mechanism of sequoiaflavone affecting gastric cancer cells. MEHTODS: Gastric cancer cell line AGS cells were treated with gradient concentrations of sequoiaflavone, and then induced by PI3K/AKT signaling pathway activator. The optimal inhibitory concentration and time of semi-inhibitory concentration of red cedar flavonoid on AGS cells were detected by CCK-8, and the changes of cell proliferation, migration and invasion ability were detected by colony formation assay, transwell assay and wound healing assay. PI3K/AKT signal pathway related proteins p-PI3K, PI3K, p-AKT and AKT were detected by western blot. RESULTS: Sequoiaflavone inhibited AGS cells in a concentration-dependent manner. The half inhibitory concentration was 0.5 mmol/L, the optimal treatment time was 48 h. The protein expression of p-PI3K and p-AKT was down regulated. The proliferation, migration and invasion of AGS cells were decreased after treated with sequoiaflavone. After treated with PI3K / AKT signal pathway activator, the protein expression level of pPI3K and p-AKT was partially reversed, and the ability of cell viability, proliferation, migration and invasion was also partially improved. CONCLUSION: Inactivation of PI3K/AKT signaling pathway caused by sequoiaflavone inhibited gastric cancer cells proliferation, migration and invasion ability.

Objective:To assess the predictive performance of the risk of cardiovascular diseases (CVD) derived from the China Kadoorie Biobank (CKB-CVD) model, prediction for atherosclerotic cardiovascular disease (ASCVD) risk in China (China-PAR) model, and the risk of fatal and nonfatal ischemic cardiovascular diseases derived from the USA-People′s Republic of China Collaborative Study (USA-PRC) model in Chinese Multi-provincial Cohort Study (CMCS).Methods:In this prospective cohort study, a total of 21 948 individuals aged ≥35 years without CVD were selected from 8 provinces and cities in China during the CMCS survey from 1992 to 2005 for 10-year follow-up. The occurrence of CVD or ASCVD events during the follow-up period was used as the gold standard. The CKB-CVD and China-PAR models were used to calculate the predicted risk of CVD events, while the USA-PRC model was used to calculate the predicted risk of ASCVD events. The discrimination of the models was evaluated using the C-statistic, and the calibration was assessed using the Hosmer-Lemeshow χ2 test and decile plot. Results:During the 10-year follow-up, a total of 955 (4.4%) CVD events, including 791 (3.6%) ASCVD events, were recorded among the study participants. The C-index for the CKB-CVD, China-PAR, and USA-PRC models were 0.775 (95% CI: 0.757-0.793), 0.781 (95% CI: 0.763-0.798), and 0.769 (95% CI: 0.750-0.789) for men, and 0.762 (95% CI: 0.737-0.788), 0.769 (95% CI: 0.745-0.794), and 0.767 (95% CI: 0.741-0.794) for women, respectively. China-PAR model showed good calibration for men ( χ2=2.20), however, both CKB-CVD and USA-PRC models demonstrated poor calibration in both men and women ( χ2>20). The results indicated that the CKB-CVD model overestimated the risk of CVD events in both males and females, while the China-PAR model underestimated the risk in females. Furthermore, the USA-PRC model underestimated the risk of ASCVD in both males and females in most decile groups, but overestimated the risk in the highest decile group. Conclusion:The CKB-CVD, China-PAR, and USA-PRC risk assessment models show some degree of deviation from the actual risk of events in the CMCS cohort, but all exhibit good discrimination.

Background::Reperfusion therapy is fundamental for ST-segment elevation myocardial infarction (STEMI). However, the details of contemporary practice and factors associated with reperfusion therapy in China are largely unknown. Therefore, this study aimed to explore reperfusion practice and its associated factors among hospitalized patients with STEMI in China.Methods::Patients with STEMI who were admitted to 159 tertiary hospitals from 30 provinces in China were included in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project from November 2014 to December 2019. The associations of the characteristics of patients and hospitals with reperfusion were examined using hierarchical logistic regression. The associations between therapies and in-hospital major adverse cardiovascular events were examined with a mixed effects Cox regression model.Results::Among the 59,447 patients, 37,485 (63.1%) underwent reperfusion, including 4556 (7.7%) receiving fibrinolysis and 32,929 (55.4%) receiving primary percutaneous coronary intervention (PCI). The reperfusion rate varied across geographical regions (48.0%-73.5%). The overall rate increased from 60.0% to 69.7% from 2014 to 2019, mainly due to an increase in primary PCI within 12 h of symptom onset. Timely PCI, but not fibrinolysis alone, was associated with a decreased risk of in-hospital major adverse cardiovascular events compared with no reperfusion, with an adjusted hazard ratio (95% confidence interval) of 0.64 (0.54,0.76) for primary PCI at <12 h, 0.53 (0.37,0.74) for primary PCI at 12 to 24 h, 0.46 (0.25,0.82) for the pharmaco-invasive strategy, and 0.79 (0.54,1.15) for fibrinolysis alone.Conclusions::Nationwide quality improvement initiatives should be strengthened to increase the reperfusion rate and reduce inequality in China.Trial registration::www.ClinicalTrials.gov, NCT02306616

Objective Mutations in polymerase gamma gene (POLG) are believed to be an important cause of early and juvenile onset of non-syndromic intractable epilepsy. The aim of this study is to investigate the incidence/prevalence of POLG pathogenic variants in epilespy patients of Han population through sequencing it.Methods Han Chinese patients with seizures prior valproic acid (VPA) exposure at Shanghai Children's Hospital were collected from 2015 to 2019. The clinical diagnosis was based on the 2014 Consensus Statement of Epilepsy by the International League against Epilepsy (ILAE). Blood sampling were performed before VPA treatment. The POLG gene DNA was sequenced by either the first or the next generation sequencing (NGS). The POLG variant burden was illustrated. Liver functions were tested to describe whether they experienced VPA toxicity. Results Totally 216 Han Chinese patients were included, aged from 1 month to 15 years old, 102 were male and 114 were female. The onset age was 1 month old to 13 years old, and the epilepsy course ranged from 2 weeks to about 3 years. VPA treatment was delivered for the generalized or intractable partial seizures at standard dosage. No patient experienced hepatic toxicity following VPA exposure. DNA sequencing data showed no patient had either a homozygous mutation or compound heterozygous mutation of POLG. Single heterozygous mutations of c.1150G>T and p.D384Y were found in 2 patients, and single heterozygous mutation of c.156_158dupGCA was found in 1 patient. None of these variants showed clinical significance. Conclusions Functional modifying POLG homozygous mutations and compound heterozygous mutations were not detected and VPA toxicity was not seen in the current study. POLG mutation frequency might be rare in Han Chinese, and standard VPA therapeutic dosage might be safe for Han Chinese patients.

OBJECTIVE: To analyze the clinical presentation and gene of 2 pedigrees with suspected oculocutaneous albinism(OCA), and provide basis for clinical classification, genetic counseling and prenatal diagnosis. METHODS: Variants were identified using next-generation sequencing(NGS) and confirmed by Sanger sequencing in 2 pedigrees with suspected OCA. The pathogenicity of the variants was analyzed according to the American College of Medical Genetics and Genomics (ACMG) standard. RESULTS: Two compound heterozygous mutations of TYR and OCA2 genes were identified respectively in 2 pedigrees with suspected OCA. The mutation of c.819+3insATATGCC in TYR and the mutation of c.1870G>C in OCA2 are first reported in this study. The pathogenicity analysis shows that two novel mutations are likely pathogenic by combination of prediction of SIFT, Polyphen-2 and Human Splicing Finder. CONCLUSION The findings of this study expand the mutational spectrum of OCA. Compound heterozygous mutations in the TYR and OCA2 gene may be responsible for clinical manifestations of 2 pedigrees with suspected OCA.
Albinism, Oculocutaneous ; DNA Mutational Analysis ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Membrane Transport Proteins ; Monophenol Monooxygenase ; Mutation ; Pedigree ; Pregnancy

Objective: To assess the use of statins and low-density lipoprotein cholesterol (LDL-C) levels at admission in hospitalized patients aged 75 years and older with acute coronary syndrome (ACS) in China. Methods: Data used in this study derived from the Improving Care for Cardiovascular Disease in China (CCC)-ACS project, a nationwide registry with 150 tertiary hospitals reporting details of clinical information of ACS patients. This study enrolled patients 75 years and older with ACS in CCC-ACS project from November 2014 to June 2017. Patients were divided into two groups according to the history of atherosclerotic cardiovascular disease (ASCVD). Pre-hospital statin use, LDL-C levels at admission and prescription of statins at discharge were reported. Results: A total of 10 899 patients 75 years and older with ACS were enrolled. The median age was 79 years and 58.7% (6 397 cases) were male. Among patients with history of ASCVD, 33.9% (1 028 cases) of them received statins before hospitalization. Among patients without history of ASCVD, 12.7% (996/7 871) received statins before hospitalization. The mean level of LDL-C was (2.4±0.9) mmol/L and LDL-C was <1.8 mmol/L in 24.7% (747 cases) of patients with history of ASCVD. The mean level of LDL-C was (2.6±0.9) mmol/L and LDL-C was <2.6 mmol/L in 51.7% (4 072 cases) of patients without history of ASCVD. At discharge, 91.2% (9 524/10 488) of patients were prescribed with statins in patients without contraindications for statin. Conclusion In elderly patients with recurrent ASCVD, there was an inadequate statin use before hospitalization and most patients did not reach the LDL-C target level when they had the recurrent events. In the elderly ACS patients without history of ASCVD, more than half of the patients had an ideal LDL-C level. It seems that ideal LDL-C level for primary prevention of ACS in elderly people needs to be reevaluated with further studies.