Association of Life's Essential 8 with all-cause mortality and risk of cancer: a prospective cohort study.

BACKGROUND: No study has concentrated on the association of LE8 with cancer risk and death. We aim to examine the association of LE8 with death and cancer. METHODS: A total of 94733 adults aged 51.42 ± 12.46 years and 77551 participants aged 54.09±12.06 years were enrolled in longitudinal and trajectory analysis respectively. Baseline LE8 was divided into three groups based on the American Heart Association criteria and three trajectory patterns by latent mixture models. We reviewed medical records and clinical examinations to confirm incident cancer during the period from 2006 to 2020. Death information was collected from provincial vital statistics offices. Cox models were used. RESULTS: 12807 all-cause deaths and 5060 cancers were documented during a 14-year follow-up. Relative to participants with high LE8 at baseline, participants with lower levels of LE8 have a significantly increased risk of mortality and incident cancer. All these risks have an increasing trend with LE8 level decreasing. Meanwhile, the trajectory analysis recorded 7483 all-cause deaths and 3037 incident cancers after approximately 10 years. The associations of LE8 with death and cancer were identical to the longitudinal study. In the subtype cancer analysis, LE8 has a strong effect on colorectal cancer risk. Moreover, the cut point is 56.67 in the association between LE8 and death, while the cut point altered to 64.79 in the association between LE8 and incident cancers. These associations were enhanced among younger adults. CONCLUSIONS: There was a significant association of LE8 with death and cancer risk, especially for the young population.

Association of stage 1 hypertension defined by the 2017 ACC/AHA guideline with cardiovascular events and mortality in Chinese adults.

BACKGROUND: The 2017 American College of Cardiology/American Heart Association (ACC/AHA) blood pressure (BP) guideline lowered the threshold defining hypertension to 130/80 mmHg. However, how stage 1 hypertension defined using this guideline is associated with cardiovascular events in Chinese adults remains unclear. This study assessed the association between stage 1 hypertension defined by the 2017 ACC/AHA guideline and clinical outcomes in the Chinese population. METHODS: Participants with stage 1 hypertension ( n = 69,509) or normal BP ( n = 34,142) were followed in this study from 2006/2007 to 2020. Stage 1 hypertension was defined as a systolic blood pressure of 130-139 mmHg or a diastolic blood pressure of 80-89 mmHg. None were taking antihypertensive medication or had a history of myocardial infarction (MI), stroke, or cancer at baseline. The primary outcome was a composite of MI, stroke, and all-cause mortality. The secondary outcomes were individual components of the primary outcome. Cox proportional hazards models were used for the analysis. RESULTS: During a median follow-up of 11.09 years, we observed 10,479 events (MI, n = 995; stroke, n = 3408; all-cause mortality, n = 7094). After multivariable adjustment, the hazard ratios for stage 1 hypertension vs. normal BP were 1.20 (95% confidence interval [CI], 1.13-1.25) for primary outcome, 1.24 (95% CI, 1.05-1.46) for MI, 1.45 (95% CI, 1.33-1.59) for stroke, and 1.11 (95% CI, 1.04-1.17) for all-cause mortality. The hazard ratios for participants with stage 1 hypertension who were prescribed antihypertensive medications compared with those without antihypertensive treatment during the follow-up was 0.90 (95% CI, 0.85-0.96). CONCLUSIONS: Using the new definition, Chinese adults with untreated stage 1 hypertension are at higher risk for MI, stroke, and all-cause mortality. This finding may help to validate the new BP classification system in China.

Weight fluctuations preceding and succeeding heart failure diagnosis: Implications for all-cause mortality.

OBJECTIVE: This study aims to explore the ramifications of weight fluctuations preceding and succeeding the identification of heart failure (HF) on all-cause mortality. METHODS: The research cohort comprised individuals engaged in the Kailuan Group's health assessments from 2006 to 2018, who were subsequently diagnosed with HF. The moment of HF recognition marked the commencement of the monitoring period, culminating either at the instance of comprehensive mortality or at the conclusion of the monitoring phase (December 31, 2021). RESULTS: Throughout an average monitoring span of 5.8±3.5 years, from the 3115 qualified participants, 957 instances (30.7%) encountered comprehensive mortality. The COX proportional hazards regression model's outcomes revealed that, post the adjustment for potential confounders, in comparison to the Q3 category, the Q1 category had the highest hazard ratios (95% confidence intervals) of 1.71 (1.43-2.05). CONCLUSION: Weight reduction before and post the HF diagnosis stands as an autonomous risk determinant for comprehensive mortality.

Association of Cumulative Exposure to Cardiovascular Health Behaviors and Factors with the Onset and Progression of Arterial Stiffness.

AIM: This study aims to explore the association of cumulative exposure to cardiovascular health behaviors and factors with the onset and progression of arterial stiffness. METHODS: In this study, 24,110 participants were examined from the Kailuan cohort, of which 11,527 had undergone at least two brachial-ankle pulse wave velocity (baPWV) measurements. The cumulative exposure to cardiovascular health behaviors and factors (cumCVH) was calculated as the sum of the cumCVH scores between two consecutive physical examinations, multiplied by the time interval between the two. A logistic regression model was constructed to evaluate the association of cumCVH with arterial stiffness. Generalized linear regression models were used to analyze how cumCVH affects baPWV progression. Moreover, a Cox proportional hazards regression model was used to analyze the effect of cumCVH on the risk of arterial stiffness. RESULTS: In this study, participants were divided into four groups, according to quartiles of cumCVH exposure levels, namely, quartile 1 (Q1), quartile 2 (Q2), quartile 3 (Q3), and quartile 4 (Q4). Logistic regression analysis showed that compared with the Q1 group, the incidence of arterial stiffness in terms of cumCVH among Q2, Q3, and Q4 groups decreased by 16%, 30%, and 39%, respectively. The results of generalized linear regression showed that compared with the Q1 group, the incidence of arterial stiffness in the Q3 and Q4 groups increased by -25.54 and -29.83, respectively. The results of Cox proportional hazards regression showed that compared with the Q1 group, the incidence of arterial stiffness in cumCVH among Q2, Q3, and Q4 groups decreased by 11%, 19%, and 22%, respectively. Sensitivity analyses showed consistency with the main results. CONCLUSIONS: High cumCVH can delay the progression of arterial stiffness and reduce the risk of developing arterial stiffness.

Detection of ion cyclotron emission by using an ion cyclotron range of frequency antennas-based diagnostic system in experimental advanced superconducting tokamak.

In the experimental advanced superconducting tokamak (EAST), a novel ion cyclotron range of frequency (ICRF) antenna-based diagnostic system is designed to measure ion cyclotron emission (ICE) driven by high-energy ions. The diagnostic system includes ICRF antenna straps, a three-tune impedance matching system, a coaxial switching system, a direct current block, and a data acquisition and storage system. Using the coaxial switching system, the ICRF antenna can be switched from the heating mode to the coupling mode between two discharges. In the 2023 EAST experiment campaign, core ICE was observed using the ICRF antenna-based diagnostic system during neutron beam injection heating, and the obtained results agreed well with the signal detected by the previous high-frequency B-dot probe-based diagnostic system.

[Effect of semaphorin-3A on the cellular stability of CD4+CD25+ regulatory T cells induced by lipopolysaccharide].

OBJECTIVE: To investigate the effect and mechanism of semaphorin-3A (Sema3A) in maintaining the cellular stability of CD4+CD25+ regulatory T cells (Tregs) induced by lipopolysaccharide (LPS). METHODS: In vitro, using immunomagnetic beads, splenic CD4+CD25+ Tregs of C57BL/6J mice were isolated and cultured. According to the random number table, the isolated cells were divided into control group (treated with anti-CD3e and anti-CD28 for polyclonal activation), LPS group (on the basis of control group, treated with LPS at the dose of 100 µg/L), LPS + nuclear factor kappa B (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC) group (treated with LPS at the dose of 100 µg/L and PDTC at the dose of 25 mg/L), LPS + phosphate buffer solution (PBS) group (treated with LPS at the dose of 100 µg/L and PBS at the volume of 10 µL), LPS + PDTC + recombinant Sema3A (rSema3A) group (treated with LPS at the dose of 100 µg/L, PDTC at the dose of 25 mg/L and rSema3A at the dose of 300 µg/L), and LPS + PBS + rSema3A group (treated with LPS at the dose of 100 µg/L, PBS at the volume of 10 µL and rSema3A at the dose of 300 µg/L). mRNA and protein expressions of the specific markers of CD4+CD25+ Tregs, including forkhead box protein P-3 (Foxp-3), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and membrane-associated transforming growth factor-ß1 (TGF-ß1m+) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence methods after 24 hours. The supernatant interleukin-10 (IL-10) and secretory type TGF-ß1 (sTGF-ß1) were detected by enzyme-linked immunosorbent assay (ELISA). The apoptotic level was detected by immunofluorescence. The demethylation of Foxp3-Tregs-specific demethylated region (Foxp-3-TSDR) was detected by methylation specific PCR (MSP) in order to reflect the cellular stability of CD4+CD25+ Tregs. DNA binding activity of NF-κB signaling pathway was determined by electrophoretic mobility shift assay (EMSA), and activity of NF-κB signaling pathway was determined by Western blotting. RESULTS: Compared with control group, LPS could increase the cellular stability, including an increase in the mRNA and protein expressions of Foxp-3, CTLA-4 and TGF-ß1m+ and secretion of IL-10 and sTGF-ß1, decrease in the level of apoptosis and increase in the methylation of Foxp-3-TSDR. At the same time, LPS increased DNA binding activity of NF-κB signaling pathway and phosphorylation levels of the major molecules of NF-κB, including inhibitory protein kinaseß (IKKß) and p65, suggesting that the mechanism of enhancing cellular stability by LPS was related to the NF-κB signaling pathway. Compared with LPS group, PBS had no effect on cellular stability and NF-κB signaling pathway. However, administration of rSema3A further promoted cellular stability and activated NF-κB signaling pathway. Compared with LPS + PBS + rSema3A group, PDTC inhibited the function of rSema3A to increase cellular stability, as the mRNA and protein expressions of Foxp-3, CTLA-4 and TGF-ß1m+ were significantly down-regulated in the LPS + PDTC + rSema3A group [Foxp-3 mRNA (2-ΔΔCt): 8.092±1.117 vs. 18.509±1.068, Foxp-3 protein (relative fluorescence intensity): 1.224±0.033 vs. 1.826±0.181; CTLA-4 mRNA (2-ΔΔCt): 3.254±0.760 vs. 11.840±0.827, CTLA-4 protein (relative fluorescence intensity): 1.305±0.058 vs. 1.842±0.111; TGF-ß1m+ mRNA (2-ΔΔCt): 3.589±1.180 vs. 8.509±0.472, TGF-ß1m+ protein (relative fluorescence intensity): 1.319±0.033 vs. 1.822±0.063, all P < 0.01], the secretion of IL-10 and sTGF-ß1 were significantly decreased [IL-10 (ng/L): 445.33±54.08 vs. 992.67±83.10, sTGF-ß1 (ng/L): 1 116.67±65.25 vs. 1 494.67±94.45, both P < 0.01], the apoptosis was significantly increased (fluorescence intensity: 0.398±0.031 vs. 0.268±0.046, P < 0.01), the methylation of Foxp-3-TSDR was significantly decreased (grey value: 0.467±0.048 vs. 1.780±0.119, P < 0.01), the DNA binding activity of NF-κB signaling pathway was significantly inhibited (grey value: 1.23±0.02 vs. 3.95±0.06, P < 0.01), and the phosphorylation levels of IKKß and p65 were significantly decreased [p-IKKß (p-IKKß/IKKß): 0.97±0.07 vs. 1.97±0.04, p-p65 (p-p65/p65): 0.95±0.08 vs. 1.93±0.06, both P < 0.01]. CONCLUSIONS: LPS increases the cellular stability of CD4+CD25+ Tregs through the NF-κB signaling pathway, and Sema3A further increases the cellular stability of CD4+CD25+ Tregs, and is related to the NF-κB signaling pathway.