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 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.

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.

Lnc-HUR1 is an HBV-related long non-coding RNA, which can promote the proliferation of hepatoma cells and the occurrence and development of liver cancer. In this study we explored the effect of lnc-HUR1 on the apoptosis of hepatocellular carcinoma cells by taking the approach of immunoblotting, quantitative real time PCR, luciferase reporter assay, chromatin immunoprecipitation (ChIP) and flow cytometry. We found that overexpression of lnc-HUR1 significantly reduced the activity of caspase3/7 and the cleavage of PARP-1, while knocking down of lnc-HUR1 significantly increased the activity of caspase3/7 and promoted the cleavage of PARP-1 in HepG2 cells treated with TGF-β, pentafluorouracil or staurosporine. Consistently, the data from Annexin-V/PI staining showed that overexpression of lnc-HUR1 inhibited apoptosis, while knockdown of lnc-HUR1 promoted apoptosis. Moreover, overexpression of lnc-HUR1 up-regulated the apoptosis inhibitor Bcl-2 and down-regulated the pro-apoptotic factor BAX at both RNA and protein levels. In the CCL4-induced acute liver injury mice model, the expression of Bcl-2 in the liver tissue of lnc-HUR1 transgenic mice was higher than that of the control mice. The data from ChIP assay indicated that lnc-HUR1 reduced the enrichment of p53 on Bcl-2 and BAX promoters. All these results indicated that lnc-HUR1 inhibited the apoptosis by promoting the expression of apoptosis inhibitor Bcl-2 and inhibiting the expression of apoptosis promoting factor BAX. Further studies showed that lnc-HUR1 regulated the transcription of Bcl-2 and BAX in HCT116 cells, but had no effect on the expression of Bcl-2 and BAX in HCT116 p53^-/- cells, indicating that lnc-HUR1 regulates the transcription of Bcl-2 and BAX dependent upon the activity of p53. In conclusion, HBV upregulated lnc-HUR1 can inhibit the apoptosis of hepatoma cells. Lnc-HUR1 inhibits apoptosis by inhibiting the transcriptional activity of p53. These results suggest that lnc-HUR1 plays an important role in the occurrence and development of HBV-related hepatocellular carcinoma.
Animals ; Annexins/pharmacology* ; Apoptosis ; Carcinoma, Hepatocellular/genetics* ; Cell Proliferation ; Hep G2 Cells ; Hepatitis B virus/metabolism* ; Humans ; Liver Neoplasms/genetics* ; Mice ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology* ; Proto-Oncogene Proteins c-bcl-2/pharmacology* ; RNA, Long Noncoding/metabolism* ; Staurosporine/pharmacology* ; Transforming Growth Factor beta/pharmacology* ; Tumor Suppressor Protein p53/pharmacology* ; bcl-2-Associated X Protein/pharmacology*

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:To assess rapid on-line evaluation (ROLE) of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for pancreatic masses.Methods:Data of patients with solid pancreatic masses who underwent EUS-FNA in Peking University First Hospital from October 2017 to October 2019 were retrospectively analyzed. Patients were divided into the ROLE group and the control group. The number of FNA passes in ROLE group was decided by the cytopathologist based on the number of pancreatic tissue cells or heteromorphic cells obtained, while that in the control group was decided by the endoscopy physician according to the visual observation of tissue strips. The cytological and histological diagnosis of EUS-FNA specimen were made by another cytopathologist. The gold standard for final diagnosis was based on the histological diagnosis of surgically resected specimens. For patients who did not undergo surgical treatment, the final diagnosis was made based on the clinical course, imaging, tumor markers and feedback on treatment. The diagnostic yield, the accuracy, the sensitivity, the specificity, FNA passes, puncture time and adverse events were compared between the two groups.Results:A total of 87 patients were enrolled, 51 in the ROLE group and 36 in the control group. The diagnostic yield of the ROLE group was higher than that of the control group without significant difference [98.0% (50/51) VS 86.1%(31/36), P=0.078]. The number of FNA passes in the ROLE group was significantly less than that in the control group (median 2 VS 3, P<0.001). No significant difference in mean FNA puncture time was found between the ROLE group and the control group (19.4 min VS 18.5 min, P=0.089). There were no significant differences between the two groups with regard to the diagnostic yield, the sensitivity, the specificity, the positive predictive value, the negative predictive value or the incidence of adverse events. Conclusion:ROLE of EUS-FNA for pancreatic solid tumor may improve tissue acquisition for puncture, reduce the number of FNA passes, and may not significantly increase the procedure time and risk of puncture.

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.

Objeetive To analyze the clinical significance of serial microproteinuria and urease detection in early diagnosis of antibiotics damage to kidney by observing the changes of urine microalbumin/creatinine ratio (mAlb/Cr),transferrin (TRF),IgG,α1-microglobulin (α1-M G),β2-microglobulin (β2-M G),retinol-binding pmtein(RBP) and N-acetyl-β-D-glucosaminidase(NAG).Methods A total of 161 children with pneumonia whose test results were normal of urine protein,blood urea nitrogen (BUN) and serum creatinine (Scr),and had no related history of kidney diseases were selected.All the patients were divided into three groups according to antibiotics for the treatment,the penicillins (penicillin G,amoxicillin and potassium clavulanate,ticarcillin and potassium clavulanate) group,the cephalosporins (cefazolin,cefuroxime,ceftriaxone,cefoperazone,ceftazidime) group and the macrolides (erythromycin,azithromycin) group.Changes of mAlb/Cr,TRF,IgG,α1-MG,β2-MG,RBP,NAG,BUN,Scr levels of the patients one week before and after use the antibiotics were observed,and statistically analyzed.Results In the penicillins group and macrolides group,the results showed that none of the serial microproteinuria and urease changed(all P ＞ 0.05).In the cephalosporins group,the urine mAlb/Cr,TRF,β2-MG and NAG were higher than before using the antibiotics [(15.56 ± 5.98) mg/g vs.(21.08 ± 10.88) mg/g,(1.61 ± 0,14)mg/L vs.(1.66 ±0.14) mg/L,(0.25 ±0.09)mg/L vs.(0.28 ±0.11)mg/L,(4.62 ±3.80) U/L vs.(4.98 ±3.97) U/L,t =-5.11,-3.24,-2.29,-2.04,P ＜ 0.05 ～ 0.001].The levels of BUN and Scr revealed no change in all the patients(all P ＞ 0.05).Conclusion Combined detection of serial microproteinuria and urease has great clinical significance in judgment and warning of early renal damage by antibiotics.