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Background: Intraindividual variability in lipid profiles is recognized as a potential predictor of cardiovascular events. However, the influence of early adulthood lipid profile variability along with mean lipid levels on future coronary artery calcium (CAC) incidence remains unclear., Methods: A total of 2395 participants (41.6% men; mean±SD age, 40.2±3.6 years) with initial CAC =0 from the CARDIA study (Coronary Artery Risk Development in Young Adults) were included. Serial lipid measurements were obtained to calculate mean levels and variability of total cholesterol, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides. CAC incidence was defined as CAC >0 at follow-up., Results: During a mean follow-up of 9.0 years, 534 individuals (22.3%) exhibited CAC incidence. Higher mean levels of total cholesterol, LDL-C, and non-HDL-C were associated with a greater risk of future CAC incidence. Similarly, 1-SD increment of lipid variability, as assessed by variability independent of the mean, was associated with an increased risk of CAC incidence (LDL-C: hazard ratio, 1.139 [95% CI, 1.048-1.238]; P =0.002; non-HDL-C: hazard ratio, 1.102 [95% CI, 1.014-1.198]; P =0.022; and triglycerides: hazard ratio, 1.480 [95% CI, 1.384-1.582]; P <0.001). Combination analyses demonstrated that participants with both high lipid levels and high variability in lipid profiles (LDL-C and non-HDL-C) faced the greatest risk of CAC incidence. Specifically, elevated variability of LDL-C was associated with an additional risk of CAC incidence even in low mean levels of LDL-C (hazard ratio, 1.396 [95% CI, 1.106-1.763]; P =0.005). These findings remained robust across a series of sensitivity and subgroup analyses., Conclusions: Elevated variability in LDL-C and non-HDL-C during young adulthood was associated with an increased risk of CAC incidence in midlife, especially among those with high mean levels of atherogenic lipoproteins. These findings highlight the importance of maintaining consistently low levels of atherogenic lipids throughout early adulthood to reduce subclinical atherosclerosis in midlife., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005130., Competing Interests: None.

Background: Non-alcoholic fatty liver disease (NAFLD) has emerged as a predominant driver of chronic liver disease globally and is associated with increased cardiovascular disease morbidity and mortality. However, the association between NAFLD and calcific aortic valve disease remains unclear. We aimed to prospectively investigate the association between NAFLD and incident aortic valve calcification (AVC), as well as its genetic relationship with incident calcific aortic valve stenosis (CAVS)., Methods: A post hoc analysis was conducted on 4226 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) database. We employed the adjusted Cox models to assess the observational association between NAFLD and incident AVC. Additionally, we conducted two-sample Mendelian randomization (MR) analyses to investigate the genetic association between genetically predicted NAFLD and calcific aortic valve stenosis (CAVS), a severe form of CAVD. We repeated the MR analyses by excluding NAFLD susceptibility genes linked to impaired very low-density lipoprotein (VLDL) secretion., Results: After adjustment for potential risk factors, participants with NAFLD had a hazard ratio of 1.58 (95% CI: 1.03-2.43) for incident AVC compared to those without NAFLD. After excluding genes associated with impaired VLDL secretion, the MR analyses consistently showed the significant associations between genetically predicted NAFLD and CAVS for 3 traits: chronic elevation of alanine aminotransferase (odds ratio = 1.13 [95% CI: 1.01-1.25]), imaging-based NAFLD (odds ratio = 2.81 [95% CI: 1.66-4.76]), and biopsy-confirmed NAFLD (odds ratio = 1.12 [95% CI: 1.01-1.24]). However, the association became non-significant when considering all NAFLD susceptibility genes., Conclusions: NAFLD was independently associated with an elevated risk of incident AVC. Genetically predicted NAFLD was also associated with CAVS after excluding genetic variants related to impaired VLDL secretion., Competing Interests: 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., (Copyright © 2024 Hao, Zeng, Lin, Guo, Li, Yang, Gao and Li.)

Background: Emerging evidence has linked daytime napping with the risk of cardiovascular events. Cardiac arrhythmias are considered an early clinical stage for cardiovascular diseases. However, whether napping frequency is associated with incident arrhythmias remains unknown., Objective: This study aimed to prospectively investigate the association between napping frequency and cardiac arrhythmias., Methods: Daytime napping frequency was self-reported in response to touchscreen questionnaires. The primary outcomes were incident arrhythmias including atrial fibrillation/flutter (AF/Af), ventricular arrhythmia, and bradyarrhythmia. Cox regression analysis was conducted on the basis of 491,117 participants free of cardiac arrhythmias from the UK Biobank. The 2-sample mendelian randomization (MR) and 1-sample MR were used to ensure a causal effect of genetically predicted daytime napping on the risk of arrhythmias., Results: During a median follow-up of 11.91 years, 28,801 incident AF/Af cases, 4132 incident ventricular arrhythmias, and 11,616 incident bradyarrhythmias were documented. Compared with never/rarely napping, usually napping was significantly associated with higher risks of AF/Af (hazard ratio, 1.141; 95% CI, 1.083-1.203) and bradyarrhythmia (hazard ratio, 1.138; 95% CI, 1.049-1.235) but not ventricular arrhythmia after adjustment for various covariates. The 2-sample MR and 1-sample MR analysis showed that increased daytime napping frequency was likely to be a potential causal risk factor for AF/Af in FinnGen (odds ratio, 1.626; 95% CI, 1.061-2.943) and bradyarrhythmia in the UK Biobank (odds ratio, 1.005; 95% CI, 1.002-1.008)., Conclusion: The results of this study add to the burgeoning evidence of an association between daytime napping frequency and an increased risk of cardiac arrhythmias including AF/Af, ventricular arrhythmia, and bradyarrhythmia., Competing Interests: Disclosures We 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., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Remnant cholesterol (RC) is implicated in the risk of cardiovascular disease. However, comprehensive population-based studies elucidating its association with aortic valve calcium (AVC) progression are limited, rendering its precise role in AVC ambiguous., Methods: From the Multi-Ethnic Study of Atherosclerosis database, we included 5597 individuals (61.8 ± 10.1 years and 47.5% men) without atherosclerotic cardiovascular disease at baseline for analysis. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), as estimated by the Martin/Hopkins equation. Using the adjusted Cox regression analyses, we examined the relationships between RC levels and AVC progression. Furthermore, we conducted discordance analyses to evaluate the relative AVC risk in RC versus LDL-C discordant/concordant groups., Results: During a median follow-up of 2.4 ± 0.9 years, 568 (10.1%) participants exhibited AVC progression. After adjusting for traditional cardiovascular risk factors, the HRs (95% CIs) for AVC progression comparing the second, third, and fourth quartiles of RC levels with the first quartile were 1.195 (0.925-1.545), 1.322 (1.028-1.701) and 1.546 (1.188-2.012), respectively. Notably, the discordant high RC/low LDL-C group demonstrated a significantly elevated risk of AVC progression compared to the concordant low RC/LDL-C group based on their medians (HR, 1.528 [95% CI 1.201-1.943]). This pattern persisted when clinical LDL-C threshold was set at 100 and 130 mg/dL. The association was consistently observed across various sensitivity analyses., Conclusions: In atherosclerotic cardiovascular disease-free individuals, elevated RC is identified as a residual risk for AVC progression, independent of traditional cardiovascular risk factors. The causal relationship of RC to AVC and the potential for targeted RC reduction in primary prevention require deeper exploration., (© 2023. The Author(s).)

Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of Prevotella copri ( P. copri ) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of P. copri and aortic calcification scores. Moreover, oral administration of live P. copri aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells in vivo , accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. In vitro and ex vivo experiments consistently demonstrated that P. copri -derived LPS ( Pc -LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, Pc -LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated Pc -LPS-induced VSMC calcification. Our study clarifies a novel role of P. copri in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including Pc -LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight P. copri and its-derived LPS as potential therapeutic targets for VC in CKD.

Background & Aims: Individuals with high blood pressure (BP) have varying risks of cardiovascular events due to other coexisting factors. We aimed to identify the predictors of long-term absence of coronary artery calcium (CAC) in individuals with high BP, which is an indicator of healthy arterial aging and can guide preventive strategies., Methods: We analyzed data from participants with high BP (≥120/80 mm Hg) in the Multi-Ethnic Study of Atherosclerosis who had baseline CAC = 0 and underwent a second CAC scanning after 10 years. We used multivariable logistic regression to evaluate the association between various risk factors for atherosclerotic cardiovascular disease (ASCVD) and long-term CAC = 0. We also calculated the area under the receiver operating characteristic curve (AUC) to predict the phenotype of healthy arterial aging in this population., Results: We included 830 participants (37.6% male, mean ± SD age of 59.4 ± 8.7 years). During follow-up, 46.5% of participants ( n  = 386) had CAC = 0, and they were younger and had fewer metabolic syndrome components. Adding ASCVD risk factors to the demographic model (age, sex, and ethnicity) moderately increased the predictive value for long-term CAC = 0 (AUC: demographic model + ASCVD risk factors vs. demographic model alone, 0.653 vs. 0.597, p  < .001; category net reclassification improvement = 0.104, p  = .044; integrated discrimination improvement = 0.040, p  < .001)., Conclusion: In individuals with high BP and initial CAC = 0, over 40% maintained CAC = 0 during a 10-year follow-up, which was associated with fewer ASCVD risk factors. These findings may have implications for preventive strategies in individuals with high BP. Clinical Trial registration number: The MESA was registered at clinical trials. gov as NCT00005487. KEY MESSAGES Nearly half (46.5%) of individuals with high blood pressure (BP) maintained a long-term absence of coronary artery calcium (CAC) during a 10-year follow-up, and this was associated with a 66.6% lower risk of atherosclerotic cardiovascular disease (ASCVD) events compared to those who developed incident CAC.Individuals with high BP, who are usually assumed to have an increased risk of ASCVD, exhibit significant heterogeneity in their ASCVD risk; those who maintain CAC = 0 have a lower ASCVD risk.Adding overall ASCVD risk factors to demographic information resulted in a moderate improvement in predicting long-term CAC = 0.

Background: Reduced lung function has been linked to cardiovascular disease, but population-based evidence on the relationship between lung function decline and coronary artery calcium (CAC) progression is rare., Methods: A total of 2694 participants (44.7% men) with a mean ± standard deviation age of 40.4 ± 3.6 years from the Coronary Artery Risk Development in Young Adults (CARDIA) were included. The rates of decline in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) over a 20-year period were calculated for each participant and categorized into quartiles. The primary outcome was CAC progression., Results: During a mean follow-up of 8.9 years, 455 (16.9%) participants had CAC progression. After adjusting for traditional cardiovascular risk factors, the hazard ratios (95% confidence intervals [CIs]) for CAC progression were higher for participants in the 2nd (Q2), 3rd (Q3), and highest quartiles (Q4) of FVC decline compared with those in the lowest quartile (Q1): 1.366 (1.003-1.861), 1.412 (1.035-1.927), and 1.789 (1.318-2.428), respectively. Similar trends were observed for the association between FEV1 and CAC progression. The association remained robust across a series of sensitivity analyses and all subgroups., Conclusions: A faster decline in FVC or FEV1 during young adulthood is independently associated with an increased risk of CAC progression in midlife. Maintaining optimal lung function during young adulthood may improve future cardiovascular health., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Excess aldosterone is implicated in vascular calcification (VC), but the mechanism by which aldosterone-MR (mineralocorticoid receptor) complex promotes VC is unclear. Emerging evidence indicates that long-noncoding RNA H19 (H19) plays a critical role in VC. We examined whether aldosterone-induced osteogenic differentiation of vascular smooth muscle cells (VSMCs) through H19 epigenetic modification of Runx2 (runt-related transcription factor-2) in a MR-dependent manner., Methods: We induced in vivo rat model of chronic kidney disease using a high adenine and phosphate diet to explore the relationship among aldosterone, MR, H19, and VC. We also cultured human aortic VSMCs to explore the roles of H19 in aldosterone-MR complex-induced osteogenic differentiation and calcification of VSMCs., Results: H19 and Runx2 were significantly increased in aldosterone-induced VSMC osteogenic differentiation and VC, both in vitro and in vivo, which were significantly blocked by the MR antagonist spironolactone. Mechanistically, our findings reveal that the aldosterone-activated MR bound to H19 promoter and increased its transcriptional activity, as determined by chromatin immunoprecipitation, electrophoretic mobility shift assay, and luciferase reporter assay. Silencing H19 increased microRNA-106a-5p (miR-106a-5p) expression, which subsequently inhibited aldosterone-induced Runx2 expression at the posttranscriptional level. Importantly, we observed a direct interaction between H19 and miR-106a-5p, and downregulation of miR-106a-5p efficiently reversed the suppression of Runx2 induced by H19 silencing., Conclusions: Our study clarifies a novel mechanism by which upregulation of H19 contributes to aldosterone-MR complex-promoted Runx2-dependent VSMC osteogenic differentiation and VC through sponging miR-106a-5p. These findings highlight a potential therapeutic target for aldosterone-induced VC., Competing Interests: Disclosures None.

Inflammation and ferroptosis crosstalk complexly with immune microenvironment of hepatocellular carcinoma (HCC), thus affecting the efficacy of immunotherapy. Herein, our aim was to identify the inflammation-associated ferroptosis (IAF) biomarkers for contributing HCC. A total of 224 intersecting DEGs identified from different inflammation- and ferroptosis-subtypes were set as IAF genes. Seven of them including ADH4, APOA5, CFHR3, CXCL8, FTCD, G6PD and PON1 were used for construction of a risk model which classified HCC patients into two groups (high and low risk). HCC patients in the high-risk group exhibited shorter survival rate and higher immune score, and were predicted to have higher respond rate in immune checkpoint inhibition (ICI) therapy. Levels of the seven genes were significantly changed in HCC tissues in comparison to adjacent tissues. After inserting the gene expression into the risk model, we found that the risk model exhibited the higher diagnostic value for distinguish HCC tissues compared each single gene. Furthermore, HCC tissues from our research group with high-risk score exhibited more cases of microsatellite instability (MSI), heavier tumour mutational burden (TMB), higher expression level of PDL1 and cells with CD8. Knockdown of APOA5 reduced HCC cell proliferation combining with elevating inflammation and ferroptosis levels. In conclusion, we considered APOA5 maybe a novel target for suppressing HCC via simultaneously elevating inflammation and ferroptosis levels, and signature constructed by seven IAF genes including ADH4, APOA5, CFHR3, CXCL8, FTCD, G6PD and PON1 can act as a biomarker for optimising the diagnosis, prognosis evaluation and immunotherapy options in HCC patients., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

The development of stable and efficient electrocatalysts for oxygen evolution reaction is of great significance for electro-catalytic water splitting. Bimetallic layered double hydroxides (LDHs) are promising OER catalysts, in which NiCu LDH has excellent stability compared with the most robust NiFe LDH, but the OER activity is not satisfactory. Here, we designed a NiCu LDH heterostructure electrocatalyst (Cu/NiCu LDH) modified by Cu nanoparticles which has excellent activity and stability. The Cu/NiCu LDH electrocatalyst only needs a low over-potential of 206 mV and a low Tafel slope of 86.9 mV dec -1 at a current density of 10 mA cm -2 and maintains for 70 h at a high current density of 100 mA cm -2 in 1M KOH. X-ray photoelectron spectroscopy (XPS) showed that there was a strong electronic interaction between Cu nanoparticles and NiCu LDH. Density functional theory (DFT) calculations show that the electronic coupling between Cu nanoparticles and NiCu LDH can effectively improve the intrinsic OER activity by optimizing the conductivity and the adsorption energy of oxygen-containing intermediates.

Purpose: This study examined the protective effects and mechanism of Lycium barbarum polysaccharides (LBP) in the context of intestinal barrier function and intestinal microbiota in mice with dextran sulfate sodium (DSS)-induced chronic ulcerative colitis (UC)., Methods: C57BL/6J male mice were assigned to a standard normal diet without DSS (control group), a normal diet with DSS (DSS group, 2% DSS given discontinuously for 3 weeks) or a normal diet supplemented with LBP (1% dry feed weight, LBP group, 2% DSS given discontinuously for 3 weeks) for a total of 8 weeks, at which point colonic tissues and caecal contents were collected., Results: LBP exerted a significant effect against colitis by increasing body weight, colon length, DAI and histopathological scores. LBP inhibited proinflammatory cytokines (IL-1β, IL-6, iNOS and TNF-α) expression, improved anti-inflammatory cytokine (IL-10) expression, promoted the expression of tight junction proteins (Occludin and ZO-1) via nuclear factor erythroid 2-related factor 2 (Nrf2) activation and decreased Claudin-2 expression to maintain the intestinal mucosal barrier. In addition, the abundances of some probiotics ( Ruminococcaceae , Lactobacillus , Butyricicoccus , and Akkermansia) were decreased with DSS treatment but increased obviously with LBP treatment. And LBP reduced the abundance of conditional pathogens associated with UC ( Mucispirillum and Sutterella ). Furthermore, LBP improved the production of short-chain fatty acids (SCFAs), including acetic acid, propionic acid, butyric acid and isobutyric acid., Conclusion: LBP can alleviate DSS-induced UC by regulating inflammatory cytokines and tight junction proteins. Moreover, LBP promotes probiotics, suppresses conditional pathogens and increases SCFAs production, showing a strong prebiotic effect.

Calcific aortic valve disease (CAVD) is a highly prevalent condition that comprises a disease continuum, ranging from microscopic changes to profound fibro-calcific leaflet remodeling, culminating in aortic stenosis, heart failure, and ultimately premature death. Ferroptosis has been hypothesized to contribute to the pathogenesis of CAVD. We aimed to study the association between ferroptosis genes and CAVD and reveal the potential roles of ferroptosis in CAVD. CAVD-related differentially expressed genes (DEGs) were identified via bioinformatic analysis of Datasets GSE51472 and GSE12644 obtained from Gene Expression Omnibus. A ferroptosis dataset containing 259 genes was obtained from the Ferroptosis Database. We then intersected with CAVD-related DEGs to identify the ferroptosis DEGs. Subsequently, protein-protein interaction networks and functional enrichment analyses were performed for ferroptosis DEGs. Then, we used miRWalk3.0 to predict the target pivotal microRNAs. An in vitro model of CAVD was constructed using human aortic valve interstitial cells. The qRT-PCR and western blotting methods were used to validate the ferroptosis DEGs identified by the microarray data. A total of 21 ferroptosis DEGs in CAVD containing 12 upregulated and nine downregulated genes were identified. The results of the Gene Set Enrichment Analysis (GSEA) and analysis of the KEGG pathway by WebGestalt indicated that the ferroptosis DEGs were enriched in six signaling pathways among which NAFLD (including IL-6, BID, and PRKAA2 genes) and HIF-1 (including IL-6, HIF-1, and HMOX1 genes) signaling pathways were also verified by DAVID and/or Metascape. Finally, the in vitro results showed that the mRNA and protein expression levels of IL-6, HIF-1α, HMOX1, and BID were higher, while the levels of PRKAA2 were lower in the Pi-treated group than those in the control group. However, the addition of ferrostatin-1 (a selective ferroptosis inhibitor) significantly reversed the above changes. Therefore, IL-6, HIF-1α, HMOX1, BID, and PRKAA2 are potential key genes closely associated with ferroptosis in CAVD. Further work is required to explore the underlying ferroptosis-related molecular mechanisms and provide possible therapeutic targets for CAVD., Competing Interests: 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., (Copyright © 2022 Li, Xiong, Zhang, Hao, Gao, Wang, Gao and Liu.)

Objective: The study aimed to assess the associations of physical activity (PA) trajectories across a 25-year span with coronary artery calcium (CAC) progression, and subsequent risk of cardiovascular disease (CVD) events., Methods: We included 2497 participants from the Coronary Artery Disease Risk Development in Young Adults study who had computed tomography-assessment of CAC at baseline (year 15: 2000-2001) and follow-up (year 20 or 25) and at least three measures of PA from year 0 to year 25. Long-term PA trajectories were determined by latent class modelling using a validated questionnaire., Results: Among the included participants, 1120 (44.9%) were men, 1418 (56.8%) were white, and the mean (SD) age was 40.4 (3.6) years. We identified three distinct PA trajectories based on PA average levels and change patterns: low (below PA guidelines, n=1332; 53.3%); moderate (meeting and slightly over PA guidelines, n=919; 36.8%) and high (about three times PA guidelines or more, n=246; 9.9%). During a mean (SD) follow-up of 8.9 (2.1) years, 640 (25.6%) participants had CAC progression. Participants in the high PA trajectory group had a higher risk of CAC progression than those in the low PA trajectory group after adjustment for traditional cardiovascular risk factors (HR 1.51; 95% CI 1.18 to 1.94). However, high PA trajectory was not associated with an increased risk of incident CVD events (HR 1.01; 95% CI 0.44 to 2.31) and the incidence of CVD events in participants with CAC progression was similar across all three PA trajectory groups (p=0.736)., Conclusion: Long-term PA about three times the guidelines or more is independently associated with CAC progression; however, no additional risk of incident CVD events could be detected., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Remnant cholesterol (RC) contributes to residual risk of atherosclerotic cardiovascular disease, but population-based evidence on the prospective relationship between RC and coronary artery calcium (CAC) progression is rare., Methods: We pooled data obtained from 6544 atherosclerotic cardiovascular disease-free individuals from the CARDIA study (Coronary Artery Risk Development in Young Adults; n=2635) and MESA (Multi-Ethnic Study of Atherosclerosis; n=3909), with a mean±SD age of 47.2±19.8 years; 3019 (46.1%) were men who completed computed tomography of CAC at baseline. RC was measured as total cholesterol minus HDL (high-density lipoprotein) cholesterol minus calculated LDL (low-density lipoprotein) cholesterol (LDL-C) estimated by using the Martin/Hopkins equation. Adjusted Cox models were used to assess the relationships between RC levels and CAC progression. We also performed discordance analyses examining the risk of CAC progression in RC versus LDL-C discordant/concordant groups using median cut points and clinically relevant LDL-C targets., Results: During a median follow-up of 8.6 years, 2778 (42.5%) participants had CAC progression. After multivariable adjustment for demographics and cardiovascular risk factors, a 1-mg/dL increase in RC levels was associated with a 1.3% higher risk of CAC progression (hazard ratio, 1.013 [95% CI, 1.008-1.017]). Results were similar when we categorized individuals by RC quartiles. Furthermore, the discordant high RC/low LDL-C group had a significantly higher risk of CAC progression than the concordant low RC/LDL-C group regarding their medians (hazard ratio, 1.195 [95% CI, 1.063-1.343]) or when setting the clinical LDL-C cut points at 100 and 130 but not 70 mg/dL. The association remained robust across a series of sensitivity analyses., Conclusions: Elevated RC levels were associated with an increased risk of CAC progression independent of traditional cardiovascular risk factors, even in individuals with optimal LDL-C levels., Registration: URL: https://www., Clinicaltrials: gov; Unique identifiers: NCT00005130 (CARDIA) and NCT00005487 (MESA).

Background: To investigate whether obesity with or without metabolic syndrome is prospectively associated with coronary artery calcium (CAC) progression and incident cardiovascular disease events., Methods: A total of 1730 participants from the CARDIA study (Coronary Artery Risk Development in Young Adults) were included (age, 40.1±3.6 years; 38.3% men), who completed computed tomography of CAC at baseline (year 15: 2000-2001) and follow-up (year 20 or 25). Metabolically healthy obesity (MHO) was defined as body mass index≥30 kg/m 2 without any metabolic syndrome components in our main analysis. Sensitivity analyses were conducted for several conditions characterizing 4 metabolic phenotypes., Results: During a mean follow-up of 9.1 years, 439 participants had CAC progression. MHO subjects had a significantly higher risk of CAC progression than their metabolically healthy normal weight counterparts (adjusted hazard ratios [95% CIs] from 1.761 [1.369-2.264] to 2.047 [1.380-3.036]) depending on the definition of MHO adopted. Obesity with unhealthy metabolic profile remained the highest significant risk of CAC progression and cardiovascular disease events whatever the definitions adopted for metabolically unhealthy status. Up to 60% of participants with MHO converted to metabolically unhealthy obesity from year 15 to year 20 or year 25. Further sensitivity analysis showed that MHO throughout carried a similar risk of incident cardiovascular disease events compared with metabolically healthy normal weight throughout., Conclusions: Different metabolic phenotypes of obesity beginning at a young age exhibit distinct risks of CAC progression and subsequent cardiovascular disease events in later midlife. MHO represents an intermediate phenotype between metabolically low- to high-risk obese individuals., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT00005130.

Background: To evaluate the clinical efficacy and safety of the modified technique utilizing the occipital bicortical screws and plate system in occipitocervical revision surgery., Methods: Between October 2010 and May 2018, 12 consecutive patients were retrospectively evaluated. All patients had posterior occipitocervical resurgery utilizing modified technique of bicortical screws and occipital plate. The measurements of extracranial occiput on midline were conducted on computed tomography (CT) scans. The thickness of the occipital bone at the location of external occipital protuberance and below 15 mm were evaluated, respectively. For the procedure, the trajectory was drilled perpendicular to the external occipital protuberance for the specified depth with a depth-limited drilling, 2 mm away from the internal bone plate, then the trajectory was deepened at intervals of 1 mm each time until reaching the internal bone plate. Meanwhile, a probe was used to explore all the walls of the trajectory. Bicortical screws were inserted to the occipital plate and the depth of penetration was less than 2 mm from the internal bone plate. Clinical efficacy and radiographic evaluation were followed up., Results: The thickest point was the external occipital protuberance, which was 15.49 ± 1.47 mm and decreased gradually on the midline to 13.41 ± 1.60 mm at below 15 mm. Twelve cases (mean age 41.17 years; range, 24-62 years), including five males and seven females, were followed up for 24.08 months (14-32 months). The interval time was 40.42 months (3-156 months) after the initial operation. At the final follow-up, JOA score increased from 8.58 ± 2.53 before surgery to 12.67 ± 1.84 (P < 0.05) and VAS score improved from 6.17 ± 1.21 to 2.08 ± 1.32 (P < 0.05). Besides, clinical symptoms were relieved in all patients after revision surgery. All patients had rigid internal fixations with bone fusion and no major complications occurred., Conclusions: Posterior occipitocervical plate-screw system with bicortical screws had the advantages of safety, simple and promising efficacy without excessive tissue release or intraspinal manipulation, proving that it's valuable as a modified technique for occipitocervical revision surgery., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Synchronization is a ubiquitous phenomenon in engineering and natural ecosystems. While the dynamics of synchronization modeled by the Kuramoto model are commonly studied in two dimensions and the state of dynamic units is characterized by a scalar angle variable, we studied the Kuramoto model generalized to D dimensions in the framework of a complex network and utilized the local synchronous order parameter between the agent and its neighbors as the controllable variable to adjust the coupling strength. Here, we reported that average connectivity of networks affects the time-dependent, rhythmic, cyclic state. Importantly, we found that the level of heterogeneity of networks governs the rhythmic state in the transition process. The analytical treatment for observed scenarios in a D-dimensional Kuramoto model at D=3 was provided. These results offered a platform for a better understanding of time-dependent swarming and flocking dynamics in nature.

Purpose: Zinc is considered protective against atherosclerosis; however, the association between dietary zinc intake and cardiovascular disease remains debated. We investigated whether dietary zinc intake was associated with coronary artery calcium (CAC) progression in the Multi-Ethnic Study of Atherosclerosis (MESA)., Methods: This analysis included 5186 participants aged 61.9 ± 10.2 years (48.8% men; 41.3% white, 25.0% black, 21.6% Hispanic, and 12.1% Chinese American) from the MESA. Dietary zinc intake was assessed by a self-administered, 120-item food frequency questionnaire at baseline (2000-2002). Baseline and follow-up CAC were measured by computed tomography. CAC progression was defined as CAC > 0 at follow-up for participants with CAC = 0 at baseline; and an annualized change of 10 or percent change of ≥ 10% for those with 0 < CAC < 100 or CAC ≥ 100 at baseline, respectively., Results: Dietary zinc intake was 8.4 ± 4.5 mg/day and 2537 (48.9%) of the included participants had CAC at baseline. Over a median follow-up of 3.4 years (25th-75th percentiles = 2.0-9.1 years), 2704 (52.1%) participants had CAC progression. In the fully adjusted model, higher dietary zinc was associated with a lower risk of CAC progression in both men (hazard ratio [HR] 0.697, 95% confidence interval [CI] 0.553-0.878; p = 0.002) and women (HR 0.675; 95% CI 0.496-0.919; p = 0.012, both comparing extreme groups). Furthermore, such an inverse association was attributable to dietary zinc intake from non-red meat (p < 0.05), rather than red meat sources (p > 0.05)., Conclusions: In this multiethnic population free of clinically apparent cardiovascular disease, higher dietary zinc intake from non-red meat sources was independently associated with a lower risk of CAC progression., Clinical Trial Registration Number: The MESA trial was registered at clinicaltrials.gov as NCT00005487., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: It remains unclear whether triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, is prospectively associated with incident peripheral arterial disease (PAD)., Methods: We included 12,320 Atherosclerosis Risk in Communities Study participants (aged 54.3 ± 5.7 years) free of a history of PAD at baseline (visit 1: 1987-1989). The TyG index was determined using ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2), and measured at 5 visits between 1987 and 2013. Incident PAD was defined as the first hospitalization with PAD diagnosis or a new onset of measured ABI < 0.90 during follow-up visits. We quantified the association of both baseline and trajectories of TyG index with incident PAD using Cox regression and logistic regression analysis, respectively., Results: Over a median follow-up of 23 years, 1300 participants developed PAD. After adjustment for traditional PAD risk factors, each 1-SD (0.58) increase in TyG index was associated with an 11.9% higher risk of incident PAD [hazard ratio, 1.119 (95% CI, 1.049-1.195)]. Results were similar when individuals were categorized by TyG index quartiles [hazard ratio, 1.239 (95% CI, 1.028-1.492); comparing extreme quartiles]. Four distinct trajectories of stable TyG indexes at various levels along the follow-up duration were identified [low (22.2%), moderate (43.2%), high (27.5%), and very high (7.1%) trajectory groups]. Compared with those with a TyG index trajectory at a low level, those participants with TyG index trajectories at high and very high levels had an even greater risk of future incident PAD [odds ratio (95%CI): 1.404 (1.132-1.740) and 1.742 (1.294-2.344), respectively] after multivariate adjustments for traditional PAD risk factors., Conclusions: Higher TyG index is independently associated with an increased risk of incident PAD. Long-term trajectories of TyG index help identify individuals at a higher risk of PAD who deserve specific preventive and therapeutic approaches., Trial Registration: Clinical trial registration number: The ARIC trial was registered at clinicaltrials.gov as NCT00005131.

Objective: The aim of this study was to analyze the role of LINC01554 in the pathogenesis of hepatocellular carcinoma (HCC) and explore the potential mechanism through which LINC01554 affects the migration and proliferation of HCC cells., Patients and Methods: LINC01554 expression in HCC tissues and its link to the prognosis of patients were analyzed by The Cancer Genome Atlas (TCGA) database. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was carried out to examine LINC01554 levels in 60 cases of HCC clinical tissues and HCC cell lines. Then, LINC01554 overexpression model was constructed using lentivirus in HCC cell lines. HCC proliferation and invasive ability were evaluated through Cell Counting Kit (CCK-8) and transwell tests, respectively. Furthermore, the potential action mechanism of LINC01554 was explored using bioinformatics analysis and in vitro cell experiments., Results: Analysis of the TCGA database revealed that LINC01554 was remarkably under-expressed in HCC tissues. Decreased expression of LINC01554 predicted a poor prognosis for patients. Besides, LINC01554 overexpression markedly blunted the proliferation and migratory capacities of HCC cells. LINC01554 competed with NGFR to bind to microRNA-3681-3p, thereby providing possible mechanisms by which LINC01554 could participate in the progression of HCC., Conclusions: This study shows for the first time that LINC01554 modulates NGFR expression by binding to microRNA-3681-3p, thereby participating in the progression of HCC.

In this paper, we propose a method to increase the field of view (FOV) in a holographic display. Different from the traditional method, a large-sized computer-generated hologram (CGH) is generated, and a holographic function screen is used in the proposed method. The CGH is formed by superposition of interference fringes. The diffraction boundary angle of the interferogram is set to be equal to the maximum diffraction angle of the reconstructed light. In the holographic reconstruction, three spatial light modulators (SLMs) arranged side by side in a linear configuration are used to load the CGH. The holographic functional screen is used for eliminating the seams between the SLMs and further enlarging the diffraction light. With the proposed method, the reconstructed light after each image point is expanded, so that the FOV can be increased effectively. Experimental results prove the feasibility of the proposed method.

The two-lane driven system is a type of important model to research some transport systems, and also a powerful tool to investigate properties of nonequilibrium state systems. This paper presents a driven bidirectional two-lane model. The dynamic characteristics of the model with periodic boundary are investigated by Monte Carlo simulation, simple mean field, and cluster mean field methods, respectively. By simulations, phase separations are observed in the system with some values of model parameters. When the phase separation does not occur, cluster mean field results are in good agreement with simulation results. According to the cluster mean field analysis and simulations, a conjecture about the condition that the phase separation happens is proposed. Based on the conjecture, the phase boundary distinguishing phase separation state and homogeneous state is determined, and a corresponding phase diagram is drawn. The conjecture is validated through observing directly the spatiotemporal diagram and investigating the coarsening process of the system by simulation, and a possible mechanism causing the phase separation is also discussed. These outcomes maybe contribute to understand deeply transport systems including the congestion and efficiency of the transport, and enrich explorations of nonequilibrium state systems.

Objective: To explore the clinical effect of negative pressure wound therapy (NPWT) in emergency limb-salvage operation of destructive injury of limb. Methods: From July 2014 to December 2017, 43 patients with destructive injury of limb in one side conformed to the inclusion criteria were admitted to our hospital. The patients were divided to NPWT group of 24 patients [ 21 males and 3 females, aged (38±10) years] and routine dressing change group of 19 patients [ 17 males and 2 females, aged (37±10) years] according to their treatment methods. After the emergency debridement, fracture external fixation, neurovascular exploration, and microsurgical repair were performed, NPWT were applied on wounds of patients in NPWT group and routine dressing change treatment on wounds of patients in routine dressing change group. On 7 to 10 days after the emergency operation, incidence of arterial embolism of patients in the two groups were calculated, and condition of wound infection of patients in the two groups were observed. Complete wound healing time and survival condition of limb were recorded. Data were processed with independent sample t test or chi-square test. Results: Incidence of arterial embolism of patients in NPWT group on 7 to 10 days after the emergency operation was 6.67% (3/45), which was close to 5.56% (2/36) of patients in routine dressing change group ( χ (2)=0.043, P >0.05). There was 1 patient with wound infection in NPWT group on 7 to 10 days after the emergency operation, obviously less than 6 patients in routine dressing change group ( χ (2)=5.847, P <0.05). Complete wound healing time of patients in NPWT group was (30±4) d, significantly shorter than (36±8) d of patients in routine dressing change group ( t =2.813, P <0.01). Limbs of 24 patients in NPWT group survived, which was close to 18 patients in routine dressing change group ( χ (2)=1.293, P >0.05). Conclusions: NPWT can significantly reduce tthe wound infection rate and shorten the time of wound healing of limb with destructive injury after emergency operation, which is worthy of popularization in clinic.

Objective: To explore the clinical efficacy of unilateral open-door laminoplasty combined with foraminotomy for cervical ossification of posterior longitudinal ligament(OPLL)., Methods: The clinical data of 45 patients with OPLL underwent surgical treatment between September 2011 and September 2015 were retrospectively analyzed. There were 26 males and 19 females with a mean age of 53.6 years old(ranged from 28 to 71 years). Among them, 24 cases received the surgery of unilateral open-door cervical laminoplasty combined with foraminotomy(combined group), and 21 cases received a single unilateral open-door cervical laminoplasty(single group). Operation time, intraoperative blood loss, complications including C₅ nerve root palsy and axial symptoms were compared between two groups. Pre-and post-operative Japanese Orthopedic Association(JOA) score, improvement rate of neurological function, Neck Disability Index(NDI) score, and cervical Cobb angle were recorded and analyzed between the two groups., Results: All the patients were followed up for 12-24 months, with an average of (14.3±2.8) months for combined groups and (13.7±3.1) months for single group, and no significant difference was found between the two groups( P >0.05). There was no significant difference in operation time and intraoperative blood loss between two groups( P >0.05). Postoperative JOA scores obtained obvious improvement in all patients( P <0.05). However, there was no significant difference between two groups for the improvement rate of neurological function( P >0.05). At final follow-up, NDI scores of combined group and single group were 13.6±1.8 and 16.1±2.4 respectively, there was significant difference between two groups( P <0.05). The incidence of C₅ nerve root palsy was lower in combined group(4.2%) than that of single group (28.6%). There was no significant difference in incidence rate of axial symptoms between two groups( P >0.05). There was no significant difference in cervical Cobb angle between pre-and post-operative conditions, or between two groups( P >0.05)., Conclusions: Unilateral open-door cervical laminoplasty combined with foraminotomy is an effective method to treat cervical OPLL, which could provide sufficient decompression of spinal cord and nerve root, prevent the C₅ nerve root palsy., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2018 by the China Journal of Orthopaedics and Traumatology Press.)

Objective: To investigate the effect and mechanism of Buyanghuanwu decoction on platelet activating factor expression in spinal cord tissue of model of acute upper cervical spinal cord injury in rats., Methods: Sixty SPF grade 3-month-old female Wistar rats were randomly divided into sham operation group, model group, methylprednisolone group and Buyanghuanwu decoction (Traditional Chinese Medicine group, TCM), with 15 rats in each group. The first day after the modeling, the methylprednisolone group were treated by injection of the tail vein for a total of 24 h, the first dose of 30 mg/kg, followed by a dose of 5.4 mg/kg·h, and 1 time per 4 h. The traditional Chinese medicine group was prepared with a medium dose of Buyanghuanwu decoction granules which were prepared into a solution containing 2 g/ml of granules, 3.5 g/kg per day gavage, was equivalent to 1 time the amount of adult consumption. The model group and the sham operation group were given equal volume of normal saline for 2 times a day for 2 weeks. The recovery of nerve function was evaluated by BBB classification at 1, 3, 7, 14 days after treatment. The expression of PAF in the segment of spinal cord injury was detected by double antibody sandwich (ELISA) method at 1, 7, and 14 d postoperatively., Results: At the first day after treatment, BBB score in model, TCM and methylprednisolone groups were lower than that of sham operation group( P <0.01), but there was no difference among the three groups( P >0.05). At 7, 14 days afer treatment, BBB score in TCM and methylprednisolone groups were higher than that of model group significantly( P <0.01); but there were no significant difference between TCM group and methylprednisolone group( P >0.05). PAF expression in TCM group and methylprednisolone group were lower than that of model group at 7, 14 day afer treatment significantly ( P <0.05); but there were no significant difference between TCM group and methylprednisolone group ( P >0.05)., Conclusions: Buyanghuanwu decoction treatment after acute upper cervical spinal cord injury can significantly improve locomotor recovery by inhibiting the expression of PAF., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2018 by the China Journal of Orthopaedics and Traumatology Press.)

Objective: To compare the clinical effect between spinal card decompression combined with traditional Chinese medicine and simple spinal card decompression for cervical spondylotic myelopathy., Methods: From June 2012 to June 2015, 73 patients with cervical spondylotic myelopathy were treated, including 42 males and 31 females, aged from 29 to 73 years old with a mean of 50.9 years old. The patients were divided into the simple operation group (34 cases) and the operation combined with traditional Chinese medicine group(39 cases) according to the idea of themselves. The anterior discectomy or subtotal corpectomy with internal fixation or posterior simple open-door decompression with lateral mass screw fixation were performed in the patients. Among them, 39 cases were treated with traditional Chinese medicine after surgery. The Japanese orthopedic association (JOA) score of spinal cord function, the improvement rate of neural function, the neck dysfunction index (NDI) score and the governor vessel stasis syndrome score were compared between two groups preoperative and postoperative 1 week, 1 month and the final follow-up respectively. The internal fixation and the condition of spinal cord decompression were observed by CT, MRI and X-rays before and after operation., Results: All the operations were successful, no injuries such as dura mater, spinal cord and nerve root were found. All the wounds were healed without infection except one patient had a superficial infection. It was solved after intermittent debridement and anti-infective therapy. Hematoma occurred in 1 case, complicated with spinal cord compression, caused incomplete paralysis, and promptly performed the re-operation to remove the hematoma without any obvious sequelae. All the patients were followed up from 12 to 24 months, (14.6±0.8) months for simple operation group and (13.5±0.7) months for operation combined with traditional Chinese medicine group, and there was no significant difference( P >0.05). The scores of JOA, NDI and the governor's vessel stasis syndrome in simple operation group were 8.31±3.15, 29.91±4.52, 6.58±1.31 before operation, and 10.21±2.58, 18.67±4.31, 8.24±1.18 one week after operation, and 11.38±2.85, 16.11±3.18, 8.91±2.11 one month after operation, and 12.21±3.12, 14.61±3.28, 9.12±1.56 at final follow-up, respectively; and in operation combined with traditional Chinese medicine group were 8.29±3.47, 30.83±4.14, 6.38±1.81before operation, and 10.48±2.39, 17.59±5.14, 8.33±1.57 one week after operation, and 12.14±3.12, 13.14±3.21, 9.55±2.49 one month after operation, and 13.85±3.34, 12.11±2.51, 10.33±1.95 at final follow-up, respectively. Postoperative JOA , NDI, and the governor vessel stasis syndrome score of two groups were significantly higher than preoperativee( P <0.05). There was no significant difference in JOA, NDI, and the governor vessel stasis syndrome score between two groups one week after operation ( P >0.05). The above items in operation combined with traditional Chinese medicine group was better than that of simple operation group one month and final follow-up after operation ( P <0.05). The improvement rate of neural function in simple operation group was (67.59±10.78)%, and in operation combined traditional Chinese medicine group was (66.88±12.15)%, there was no significant difference between two groups( P >0.05). There were no complications such as internal fixation failure or re-dislocation of atlas by postoperative CT, MRI and X-rays examination., Conclusions: Spinal card decompression for the treatment of cervical spondylotic myelopathy can extend the spinal canal, relieve the compression of nerve, achieve the deoppilation of governor vessel, the regulation of qi and blood, the restore of Yangqi, combined with traditional Chinese medicine of activating blood removing stasis, warming yang and activating meridians, reinforcing liver benefiting kidney, which may obtain better clinical effect., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2018 by the China Journal of Orthopaedics and Traumatology Press.)

Objective: To explore the effect and underlying mechanism of decompression(DE)combined with Governor Vessel(GV)electro-acupuncture(EA) on rats with acute severe upper cervical spinal cord compression injury., Methods: Thirty SPF rats were randomly divided into 5 groups(control group A, B and experiment group C, D, E), 6 rats in each group. The model of acute severe upper cervical spinal cord compression injury were made by forcing a balloon catheter put in atlas pillow clearance. The group A was blank one, the group B put balloon catheter in atlas pillow clearance without forcing, and the group C, D, E sustained compressed for 48 h. The group C received electric acupuncture intervention, selecting the Baihui and Dazhui point, having the continuous wave and frequency of 2 Hz, with the treatment time of 15 min and continuous treatment for 14 d; the group D received methylprednisolone intervention, injected by caudal vein; the group E did not received any intervention again. The arterial blood and injured spinal cord tissue of all the rats were obtained after 14 days' treatment, and BBB score was used to evaluate the change of each group hind limbs motor function, the contents of platelet activating factor(PAF) in injured spinal cord tissue and blood serum were assess by ELISA method; the Caspase-9 expression for each group after 14 days' treatment was assess by Western blot method., Results: BBB scores were(21.000±0.000) points at the 6 time points, that was, 1 h, 48 h after forcing in control group, 24 h, 3 d, 7 d, 14 d after treating in experiment group; the score of experimental groups (group C, D, E) were always lower than control groups(group A, B); compared with group E, group C and D were significantly higher( P <0.05); and there was no significant difference between group C and group D( P >0.05). The results of PAF by ELISA method to measure:the concentration of serum PAF, there was no statistical difference among group A, B, D, E ( P >0.05), group C was lower than the other groups ( P <0.05); the concentration of tissue PAF, there was no significant difference between group A and group B( P >0.05), group D was significantly higher than that of group A, B, and C( P <0.05), group E was the highest one than that of the other groups( P <0.05). Western blot med tests showed that the Caspase-9 protein expression in group A and B was similar ( P >0.05), group C was higher than that of group A and B( P <0.05), group D was higher than group A, B and C( P <0.05), group E was the highest than that of group A, B, C and D ( P <0.05)., Conclusions: Decompression and Governor Vessel electro-acupuncture on acute severe upper cervical spinal cord compression injury had a better effect compare with decompression and methylprednisolone or simple decompression only, its mechanism may be related to lower the PAF levels and downregulating Caspase-9 protein expression in spinal injury tissue., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2018 by the China Journal of Orthopaedics and Traumatology Press.)

Background: Homocysteine-lowering intervention with folate was recently shown to be able to increase day-night difference of blood pressure (BP) in humans indicating a potential relationship between homocysteine and circadian BP variation. We thus sought to investigate the association between plasma total homocysteine level (tHcy) and circadian BP variation in hypertensive adults., Methods: We enrolled 244 eligible dipping and 249 nondipping BP status adults from 560 adults who were randomly sampled from 5,233 Chinese hypertensive adults who received ambulatory BP monitoring (ABPM). We further enrolled 390 adults with CC/CT genotypes of the methylenetetrahydrofolate reductase (MTHFR) and 79 TT genotype who received ABPM at the same time from 1858 hypertensive adults with MTHFR polymorphisms detection., Results: Plasma tHcy in nondippers was significantly higher than dippers (P < 0.001). Simple linear analysis revealed that tHcy significantly correlated with nocturnal systolic BP fall (r = -0.145, P = 0.001) and diastolic BP fall (r = -0.141, P = 0.002). Multivariate logistic regression analysis further identified tHcy as an independent factor correlated with the presence of nondipping BP status in hypertensive adults (odds ratio: 1.873, 95% confidence interval: 1.171-2.996, P = 0.009). The percentage of dipping BP status was 19.49% or 8.86% and the percentage of nondipping BP status was 80.51% or 91.14% in CC/CT or TT genotypes, respectively. The above different between CC/CT and TT genotypes was significant (P = 0.024)., Conclusions: These results indicated that high homocysteine levels associate with disturbed circadian BP variation in Chinese hypertensive adults., (© American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Pulmonary hypertension (PH) is a complex and multifactorial disease. An inability to fully unravel the molecular complexities has led to various clinical challenges in developing new therapies for this disease. Noncoding RNAs (ncRNAs) are RNA molecules with limited ability of coding proteins. The amount of ncRNAs is up to 98% of the whole genome's transcripts. Many ncRNAs with a regulatory function of genes have been identified to date and found to act at various steps along the protein biosynthetic process, which includes transcription, RNA maturation, translation, and protein degradation. These discoveries are fueling a new era in understanding the pathophysiology and therapeutic pathways of PH. In this chapter, we discuss the emerging role of noncoding RNAs in PH as well as other pulmonary diseases.

Background: Continuous negative pressure drainage (CNPD) is widely used after lower lumbar internal fixation; however, it may cause tremendous blood loss and lead to postoperative hemorrhagic anemia. The present study explored the efficacy and safety of improved intermittent-clamped drainage (ICD) for lower lumbar internal fixation., Methods: This was a prospective study that included 156 patients with decompression of the spinal canal and internal fixation for the first time from January 2012 to December 2014. The patients were randomly divided into ICD group and CNPD group, and each group had 78 cases. A drainage tube was placed under the deep fascia in all patients within 10 min after the commencement of wound closure. The postoperative drainage amount at different time points, the hemoglobin level, and postoperative complications were recorded and compared between the two groups. Shapiro-Wilk test, independent samples t-test, and Mann-Whitney U-test were used in this study., Results: The drainage amount was significantly reduced in the ICD group, as compared with the CNPD group (Z = 10.74, P < 0.01). The mean total drainage amount (in ml) of the single-segment and two-segment procedures was significantly greater in the CNPD group than the ICD group (Z = 10.63 and 10.75, respectively; P < 0.01). For the adverse events, there was no significant difference in postoperative temperature, wound problem, and complications between the two groups., Conclusions: The present study showed a statistically significant reduction in postoperative drainage amount between ICD and CNPD groups, and ICD is an effective, convenient, and safe method for routine use in lower lumbar surgery. It is essential to focus on the effect of clamping drainage with long-segment surgical procedure and complex lumbar disease in the further investigation, as well as the effect of clamping on long-term functional outcomes., Competing Interests: There are no conflicts of interest.

Objective: Bortezomib plus dexamethasone (BD) and bortezomib, epirubicin plus dexamethasone (PAD) are both front-line regimens of multiple myeloma. This study aimed to assess the efficacy and safety of BD versus PAD regimens in multiple myeloma., Methods: All 208 patients with newly diagnosed multiple myeloma using either BD or PAD front-line regimens were enrolled between November 2006 and July 2014. Front-line chemotherapy regimens were 2-7 cycles. Response rates, overall survival, progression-free survival, and adverse effects were retrospectively analyzed., Results: (1) In PAD group, the overall response rate was 82.9% [complete response(CR) 28.6%, very good partial response(VGPR) 12.9%], which was similar as that in BD group [70.3% (CR 26.8%, VGPR 5.1%), P=0.049]. The estimated median progression-free survival was 34.0 months in PAD group versus 25.0 months in BD group (P=0.010). (2) The triplet regimen has a higher accumulated response rate along with chemotherapy cycles, but it didn't show any difference with the doublet regimen. (3) In elderly patients (>65 years old), the overall response rates in two groups had no significant difference (P=0.769), while in patients ≤65 years old, PAD regimen were more effective than BD regimen (P=0.037). (4) Grade 3 and 4 adverse events were recorded with a higher number of patients in the PAD group than those in the BD group., Conclusions: Compared with BD regimen, PAD regimen improves the initial response rates, especially deep responses, as well as progression-free survival in patients with newly diagnosed multiple myeloma. However, more severe toxicities are accordingly higher. In elderly patients, overall response rate, estimated median progression-free survival, and median overall survival are all comparable in both regimens.

Driven diffusive systems are important models in nonequilibrium state statistical mechanics. This paper studies an asymmetric exclusion process model with nearest rear neighbor interactions associated with energy. The exact flux expression of the model is obtained by a cluster mean-field method. Based on the flux expression, the properties of the fundamental diagram have been investigated in detail. To probe the energy's influence on the coarsening process of the system, Monte Carlo simulations are carried out to acquire the monotonic phase boundary in energy-density space. Above the phase boundary, the system is inhomogeneous and the normalized residence distribution p(s) is nonmonotonically decreasing. Under the phase boundary, the system is homogeneous and p(s) is monotonically decreasing. Further study comparatively shows that the system has turned into a microscopic inhomogeneous state from a homogeneous state before the system current arrives at maximum, if nearest rear neighbor interactions are strong. Our findings offer insights to deeply understand the dynamic features of nonequilibrium state systems.

Driven diffusive systems have been a paradigm for modelling many physical, chemical, and biological transport processes. In the systems, spatial correlation plays an important role in the emergence of a variety of nonequilibrium phenomena and exhibits rich features such as pronounced oscillations. However, the lack of analytical results of spatial correlation precludes us from fully understanding the effect of spatial correlation on the dynamics of the system. Here we offer precise analytical predictions of the spatial correlation in a typical driven diffusive system, namely facilitated asymmetric exclusion process. We find theoretically that the correlation between two sites decays exponentially as their distance increases, which is in good agreement with numerical simulations. Furthermore, we find the exponential decay is a universal property of macroscopic homogeneous state in a broad class of 1D driven diffusive systems. Our findings deepen the understanding of many nonequilibrium phenomena resulting from spatial correlation in driven diffusive systems.

Background: The footprint of most prostheses is designed according to Caucasian data. Total disc replacement (TDR) has been performed widely for cervical degenerative diseases in China. It is essential to analyze the match sizes of prostheses footprints and Chinese cervical anatomic dimensions in our study., Methods: The anatomic dimensions of the C4-C7 segments of 138 patients (age range 16-77 years) in a Chinese population were measured by computed tomography scans. We compared the footprints of the most commonly used cervical disc prostheses (Bryan: Medtronic, Minneapolis, MN, USA; Prestige LP: Medtronic, Fridley, Minnesota, USA; Discover: DePuy, Raynham, MA, USA; Prodisc-C: Synthes, West Chester, PA, USA) in China with Chinese cervical anatomic dimensions and assessed the match of their size., Results: The mismatch of available dimensions of prostheses and anatomic data of cervical endplates ranged from 17.03% (C4/C5, Prestige LP, Prodisc-C) to 57.61% (C6/C7, Discover) in the anterior-posterior (AP) diameter, and 35.51% (C4/C5, Prodisc-C, Prestige LP) to 94.93% (C6/C7, Bryan) in the center mediolateral (CML) diameter. About 21.01% of endplates were larger than the largest prostheses in the AP diameter and 57.25% in the CML diameter. All available footprints of prostheses expect the Bryan with an unfixed height, can accommodate the disc height (DH), however, 36.23% of the middle DH was less than the smallest height of the prostheses. The average disc sagittal angles (DSAs) of C4-C7 junctions were 5.04°, 5.15°, and 4.13° respectively. Only the Discover brand had a built-in 7° lordotic angle, roughly matching with the DSA., Conclusions: There is a large discrepancy between footprints of prostheses and Chinese cervical anatomic data. In recent years, possible complications of TDR related with mismatch sizes are increasing, such as subsidence, displacement, and heterotopic ossification. Manufacturers of prostheses should introduce or produce additional footprints of prostheses for Chinese TDR.

This paper has studied spontaneous symmetry breaking (SSB) phenomenon in two types of two-channel asymmetric simple exclusion processes (ASEPs). One common feature of the two systems is that interactions for each species of particle happen at only one site, and the system reduces to two independent ASEPs when interaction vanishes. It is shown that with the weakening of interaction, the SSB is suppressed. More interestingly, the SSB disappears before the interaction is eliminated. Our work thus indicates that local interaction has to be strong enough to produce SSB. The mean-field analysis has been carried out, and the results are consistent with the simulation ones.

This paper studies unidirectional pedestrian flow by using a lattice gas model with parallel update rules. Game theory is introduced to deal with conflicts that two or three pedestrians want to move into the same site. Pedestrians are either cooperators or defectors. The cooperators are gentle and the defectors are aggressive. Moreover, pedestrians could change their strategy. The fundamental diagram and the cooperator fraction at different system width W have been investigated in detail. It is found that a two-lane system exhibits a first-order phase transition while a multilane system does not. A microscopic mechanism behind the transition has been provided. Mean-field analysis is carried out to calculate the critical density of the transition as well as the probability of games at large value of W. The spatial distribution of pedestrians is investigated, which is found to be dependent (independent) on the initial cooperator fraction when W is small (large). Finally, the influence of the evolutionary game rule has been discussed.

This paper studies an extended parallel asymmetric exclusion process, in which the anticipation effect is taken into account. The fundamental diagram of the model has been investigated via cluster mean field analysis. Different from previous mean field analysis, in which the n -cluster probabilities P(σ{i},…,σ{i+n-1}) involve the (n+2) -cluster probabilities P(τ{i-1},…,τ{i+n}) , our mean-field analysis is asymmetric because the three-cluster probabilities P(σ{i},σ{i+1},σ{i+2}) involve the six-cluster probabilities P(τ{i-1},…,τ{i+4}) . We find an excellent agreement between Monte Carlo simulations and cluster mean field analysis, which indicates that the mean field analysis might give the exact expression.

This paper studies unidirectional pedestrian flow in a channel using the lattice gas model with parallel update rule. The conflict (i.e., several pedestrians intend to move to the same site) is solved by introducing probabilities as in floor field models. The fundamental diagram (FD) is investigated and it is found that when the drift strength D≲0.5, the FD is a concave curve. With the further increase in drift strength, a turning point appears on FD. The empirical findings show that both concave FD and FD with a turning point exist. Thus, the model might be able to reproduce both by tuning drift strength. It is also shown that in the special case D=1, two congested branches exist in the FD. We have carried out mean-field analysis of the FD and the mean-field results are in approximate agreement with simulations when the drift strength D is small. A comparison with random sequential update rule model is also made.

The authors report on gas sensing properties of SnO2 hollow spheres with diverse microstructures, which are synthesized through controlled precipitation of Sn(OH)4 layers on carbon sphere templates, followed by heat treatment at different temperatures. Hollow spheres derived at 973 K consist of monolayer SnO2 grains, which lead to a huge activated surface area. The sensitivity of sensors based on SnO2 monolayer hollow spheres is up to 51 at 100 ppm ethanol, which is much higher than that of two other samples. We attribute this enhancement mostly to the enhanced depletion effect arising from the increased exposed surface. Our results suggest a direction for improving the performance of gas sensors by using monolayer porous hollow spheres.