Alveolar bone morphology in patients with palatally-displaced maxillary lateral incisors before and after orthodontic treatment: A cone-beam computed tomography study.

INTRODUCTION: Palatal displacement of maxillary anterior teeth is common in clinical practice. Previous studies have reported that the labial bone around palatally-displaced incisors is thinner than that around normally-placed teeth. Therefore, it is necessary to elucidate alveolar bone changes after alignment to guide orthodontic treatment. In this study, we investigated the alveolar bone changes around palatally-displaced maxillary lateral incisors before and after treatment, and the effects of extraction and age using cone-beam computed tomography. METHODS: In this retrospective study, 55 patients with unilateral palatally-displaced maxillary lateral incisors were included. Three-dimensional alveolar bone changes were measured at three levels (25%, 50% and 75% of the root length) using cone-beam computed tomography. Group comparisons were made between displaced and control teeth, extraction and non-extraction groups, and adult and minor groups. RESULTS: After orthodontic treatment, labiopalatal and palatal alveolar bone widths decreased at all measured levels. Labial alveolar bone width increased significantly at P25, but decreased at P75. Concavity decreased, while tooth-axis angle, tooth length, B-CEJ and P-CEJ increased. Changes in LB and LP at P75, B-CEJ and P-CEJ were statistically significant. After treatment, the tooth-axis angle on the PD side increased by 9.46°. The change in tooth-axis angle on the PD side was significantly smaller, and LB and LP decreased more at P75, in the extraction group. CONCLUSIONS: Compared to the control teeth, alveolar bone thickness and height for the displaced teeth decreased more significantly after treatment. Tooth extraction and age also influenced alveolar bone changes.

Primary mucinous tumors of the renal pelvis: Clinical, histopathological, and molecular analysis of three cases.

Primary mucinous tumors of the renal pelvis are extremely rare and pose challenges in terms of diagnosis and treatment. This study reviewed the clinical and pathological characteristics of mucinous tumors of the renal pelvis, including mucinous cystadenocarcinomas and mucinous cystadenomas. Immunohistochemical analysis was conducted in three cases, along with KRAS gene detection using the Amplification Refractory Mutation System (ARMS) method. The results revealed mucinous epithelium with acellular mucinous pools in all cases, and acellular mucinous pools were observed in the renal parenchyma and perirenal fat capsules. All tumors expressed CK20 and CDX2, and one case showed KRAS gene mutation. The study suggests that mucinous cystadenomas of the renal pelvis may exhibit borderline biological behaviors. This study is the first to report a KRAS gene mutation in a mucinous cystadenoma of the renal pelvis, offering valuable insights into the diagnosis and treatment of this rare condition.

Relationship between cumulative exposure to triglyceride-glucose index and heart failure: a prospective cohort study.

BACKGROUND: High triglyceride-glucose index (TyG) is a major risk factor for heart failure, but the long-term effect of high TyG index on the risk of developing heart failure remains unclear. Therefore, we aimed to determine the relationship between the cumulative exposure to TyG index and the risk of heart failure. METHODS: A total of 56,149 participants from the Kailuan Study, who participated in three consecutive health examinations in 2006, 2008, and 2010 and had no history of heart failure or cancer were recruited for this study. The cumulative TyG index was calculated as the weighted sum (value × time) of the mean TyG index for each time interval. The participants were placed into quartiles based on their cumulative TyG index. The study ended on December 31, 2020, and the primary outcome was new-onset heart failure during the follow-up period. In addition, a Cox proportional hazards regression model and a restricted cubic spline analysis were used to further evaluate the relationship between cumulative TyG index and the risk of heart failure. RESULTS: During a median follow-up period of 10.04 years, a total of 1,312 new heart failure events occurred. After adjustment for potential confounding factors, the Cox regression analysis showed that the hazard ratios (95% confidence intervals) for the risk of heart failure in the Q2, Q3, and Q4 groups were 1.02 (0.83,1.25), 1.29 (1.07,1.56) and 1.40 (1.15,1.71), respectively, vs. the Q1 group. The subgroup analysis showed a significant interaction between cumulative TyG index and BMI or waist circumference, but there was no interaction between age, sex and cumulative TyG index. The restricted cubic spline analysis showed a dose-response relationship between cumulative TyG index and the risk of heart failure. In addition, the sensitivity analysis generated results that were consistent with the primary results. CONCLUSIONS: High cumulative TyG index is associated with a higher risk of heart failure. Thus, the TyG index may be useful for the identification of individuals at high risk of heart failure. The present findings emphasize the importance of the long-term monitoring of the TyG index in clinical practice.

Temporal relationship between triglyceride-glucose index and blood pressure and their joint cumulative effect on cardiovascular disease risk: a longitudinal cohort study.

BACKGROUND: Concurrent insulin resistance and elevated blood pressure are commonly observed in cardiovascular disease (CVD) and have long been proposed to contribute to CVD. However, the temporal relationship between them and the effect of their cumulative co-exposure on future incident CVD remains unclear. METHODS: Longitudinal analysis of data on 57,192 participants from a real-world, prospective cohort study (Kailuan Study) was performed to address the temporal relationship between Triglyceride-Glucose Index (TyG, calculated as ln [TG (mg/dL) × FBG (mg/dL)/2]) and blood pressure (BP) assessed by cross-lagged analyses in an approximately 4-year exposure period (2006/2007 to 2010/2011). After excluding 879 participants with known diabetes, 56,313 nonCVD participants were included for further analysis of the CVD outcome. Cox regression models were used to examine the hazard ratios (HRs) upon the cumulative TyG (CumTyG) and BP(CumBP) in the exposure period. RESULTS: The standard regression coefficient from baseline TyG to follow-up systolic BP was 0.0142 (95% CI 0.0059-0.0226), which was greater than the standard regression coefficient from baseline systolic BP to follow-up TyG (- 0.0390; 95% CI - 0.0469 to - 0.0311). The same results were observed in the cross-lag between TyG and diastolic blood pressure [0.0271 (0.0185 to 0.0356) vs. - 0.0372 (- 0.0451 to - 0.0293)]. During a median follow-up of 9.98 years, 3981 CVD cases occurred. Significant interactions were observed between the median CumTyG (8.61) and CumSBP thresholds (130, 140 mmHg) (P = 0.0149), the median CumTyG (8.61) and CumDBP thresholds (80, 90 mmHg) (P = 0.0441). Compared to CumTyG < 8.61 and CumSBP < 130 mmHg, after adjusting for potential confounding factors, the HR gradually increased in the high co-exposure groups. The hazard ratios (HRs) and 95% confidence intervals (CIs) for Q2-Q6 were 1.39 (1.24, 1.57), 1.94 (1.69, 2.22), 2.40 (2.12, 2.71), 2.74 (2.43, 3.10), and 3.07 (2.74, 3.45). Additionally, the CVD risks in the co-exposure were more prominent in younger participants. CONCLUSIONS: These findings suggest that elevated TyG has a greater impact on future blood pressure changes than vice versa. Dual assessment and management of insulin resistance and blood pressure contribute to the prevention of CVD, especially in younger individuals.

Relationship between the cumulative exposure to atherogenic index of plasma and ischemic stroke: a retrospective cohort study.

BACKGROUND: Atherogenic index of plasma (AIP) has been demonstrated as a surrogate marker for ischemic stroke, but there is limited evidence for the effect of long-term elevation of AIP on ischemic stroke. Therefore, we aimed to characterize the relationship between cumulative exposure to AIP and the risk of ischemic stroke. METHODS: A total of 54,123 participants in the Kailuan Study who attended consecutive health examinations in 2006, 2008, and 2010 and had no history of ischemic stroke or cancer were included. The time-weighted cumulative AIP (cumAIP) was calculated as a weighted sum of the mean AIP values for each time interval and then normalized to the total duration of exposure (2006-2010). Participants were divided into four groups according to quartile of cumAIP: the Q1 group, ≤-0.50; Q2 group, - 0.50 to - 0.12; Q3 group, - 0.12 to 0.28; and Q4 group, ≥ 0.28. Cox proportional hazard models were used to evaluate the relationship between cumAIP and ischemic stroke by calculating hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: After a median follow-up of 11.03 years, a total of 2,742 new ischemic stroke events occurred. The risk of ischemic stroke increased with increasing quartile of cumAIP. After adjustment for potential confounders, Cox regression models showed that participants in the Q2, Q3, and Q4 groups had significantly higher risks of ischemic stroke than those in the Q1 group. The HRs (95% CIs) for ischemic stroke in the Q2, Q3, and Q4 groups were 1.17 (1.03, 1.32), 1.33 (1.18, 1.50), and 1.45 (1.28, 1.64), respectively. The longer duration of high AIP exposure was significantly associated with increased ischemic stroke risk. CONCLUSIONS: High cumulative AIP is associated with a higher risk of ischemic stroke, which implies that the long-term monitoring and maintenance of an appropriate AIP may help prevent such events.

Supra-additive effect of chronic inflammation and atherogenic dyslipidemia on developing type 2 diabetes among young adults: a prospective cohort study.

BACKGROUND: Both elevated inflammation and atherogenic dyslipidemia are prominent in young-onset diabetes and are increasingly identified as biologically intertwined processes that contribute to diabetogenesis. We aimed to investigate the age-specific risks of type 2 diabetes (T2D) upon concomitant chronic inflammation and atherogenic dyslipidemia. METHODS: Age-stratified Cox regression analysis of the risk of incident diabetes upon co-exposure to time-averaged cumulative high-sensitivity C-reactive protein (CumCRP) and atherogenic index of plasma (CumAIP) among 42,925 nondiabetic participants from a real-world, prospective cohort (Kailuan Study). RESULTS: During a median 6.41 years of follow-up, 3987 T2D developed. Isolated CumAIP and CumCRP were significantly associated with incident T2D in the entire cohort and across all age subgroups. Both CumAIP and CumCRP were jointly associated with an increased risk of diabetes (P-interaction = 0.0126). Compared to CumAIP < -0.0699 and CumCRP < 1 mg/L, co-exposure to CumAIP ≥ - 0.0699 and CumCRP ≥ 3 mg/L had a significant hazard ratio (HR) [2.55 (2.23-2.92)] after adjusting for socio-demographic, life-style factors, family history of diabetes, blood pressure, renal function and medication use. The co-exposure-associated risks varied greatly by age distribution (P-interaction = 0.0193): < 40 years, 6.26 (3.47-11.28); 40-49 years, 2.26 (1.77-2.89); 50-59 years, 2.51 (2.00-3.16); 60-69 years, 2.48 (1.86-3.30); ≥ 70 years, 2.10 (1.29-3.40). In young adults (< 45 years), both exposures had a significant supra-additive effect on diabetogenesis (relative excess risk due to interaction: 0.80, 95% CI 0.10-1.50). CONCLUSIONS: These findings highlight the need for age-specific combined assessment and management of chronic inflammation and dyslipidemia in primary prevention against T2D, particularly for young adults. The clinical benefit derived from dual-target intervention against dyslipidemia and inflammation will exceed the sum of each part alone in young adults.

Cumulative exposure to high remnant-cholesterol concentrations increases the risk of cardiovascular disease in patients with hypertension: a prospective cohort study.

BACKGROUND: The relationship of cumulative remnant-cholesterol (Cum-RC) concentration with the risk of cardiovascular disease (CVD) in patients with hypertension remains unclear. METHODS: We studied data for 28,698 individuals for whom three consecutive total cholesterol, high-density lipoprotein-cholesterol (HDL-C), and triglyceride concentrations were available, and who did not have CVD (14,349 with hypertension and 14,349 without), that was collected between 2006 and 2010. Participants with hypertension were placed into four groups based on Cum-RC quartile: a Q1 group (< 26.40 mg/dl), a Q2 group (26.40-39.56 mg/dl), a Q3 group (39.57-54.65 mg/dl), and a Q4 group (≥ 54.66 mg/dl). Cox proportional hazards models were used to evaluate the relationship between Cum-RC and the risk of CVD. RESULTS: Over a median 10.9 (interquartile range, 10.5-11.3) years, 1,444 participants with hypertension developed CVD. After adjustment for multiple potential confounding factors, and compared with the Q1 Cum-RC group of the participants with hypertension, the adjusted hazard ratios for CVD for the Q2-Q4 groups were 1.07(0.92,1.26), 1.08(0.91,1.28), and 1.26(1.03,1.54) (P = 0.0405); those for myocardial infarction were 1.51(1.00,2.31), 2.02(1.22,3.27), and 2.08(1.41,3.28) (P < 0.0001); and those for ischemic stroke were 1.02(0.84,1.24), 1.04(0.86,1.25), and 1.29(1.02,1.62), respectively (P = 0.0336). However, no significant relationship was found between Cum-RC and the risk of hemorrhage stroke. At the same Cum-RC, the risk of CVD was significantly higher in participants with hypertension than in those without. CONCLUSIONS: A consistently high remnant-cholesterol concentration increases the risk of CVD in individuals with hypertension. Therefore, the achievement of blood pressure and RC concentration targets should help reduce the risk of CVD in individuals with hypertension.

Deficiency of neuropeptide Y attenuates neointima formation after vascular injury in mice.

BACKGROUND: Restenosis after percutaneous coronary intervention (PCI) limits therapeutic revascularization. Neuropeptide Y (NPY), co-stored and co-released with the sympathetic nervous system, is involved in this process, but its exact role and underlying mechanisms remain to be fully understood. This study aimed to investigate the role of NPY in neointima formation after vascular injury. METHODS: Using the left carotid arteries of wild-type (WT, NPY-intact) and NPY-deficient (NPY-/-) mice, ferric chloride-mediated carotid artery injury induced neointima formation. Three weeks after injury, the left injured carotid artery and contralateral uninjured carotid artery were collected for histological analysis and immunohistochemical staining. RT-qPCR was used to detect the mRNA expression of several key inflammatory markers and cell adhesion molecules in vascular samples. Raw264.7 cells were treated with NPY, lipopolysaccharide (LPS), and lipopolysaccharide-free, respectively, and RT-qPCR was used to detect the expression of these inflammatory mediators. RESULTS: Compared with WT mice, NPY-/- mice had significantly reduced neointimal formation three weeks after injury. Mechanistically, immunohistochemical analysis showed there were fewer macrophages and more vascular smooth muscle cells in the neointima of NPY-/- mice. Moreover, the mRNA expression of key inflammatory markers such as interleukin-6 (IL-6), transforming growth factor-ß1 (TGF-ß1), and intercellular adhesion molecule-1 (ICAM-1) was significantly lower in the injured carotid arteries of NPY-/- mice, compared to that in the injured carotid arteries of WT mice. In RAW264.7 macrophages, NPY significantly promoted TGF-ß1 mRNA expression under unactivated but not LPS-stimulated condition. CONCLUSIONS: Deletion of NPY attenuated neointima formation after artery injury, at least partly, through reducing the local inflammatory response, suggesting that NPY pathway may provide new insights into the mechanism of restenosis.

Continuous Hypobaric Hypoxia may Promote Atherosclerosis Progression in Apolipoprotein E-deficient Mice.

Background: Intermittent normobaric hypoxia can promote the progression of atherosclerotic plaques. However, the effect of continuous hypobaric hypoxia (CHH), which is a major feature of high-altitude environment, on atherosclerosis has not been investigated thoroughly. Materials and Methods: After eight weeks of high-cholesterol diet, 30 male ApoE-/- mice were randomly divided into control and CHH groups. Mice in the CHH group lived in a hypobaric chamber with an oxygen content of 10% and air pressure of 364 mmhg (equal to 5,800 m altitude above sea level) for 4 weeks, while mice in the control group lived in normoxia condition. Then all mice were euthanized and the atherosclerotic lesion size and plaque stability in the aortic root were assessed. Intraplaque angiogenesis was characterized by immunostaining of CD31 and endomucin, which are identified as specific markers of vascular endothelial cells. Immunohistochemistry and qRT-PCR were performed to measure inflammatory cytokines. Results: Four weeks of CHH exposure promoted the growth of atherosclerotic lesions (p=0.0017) and decreased the stability of atherosclerotic plaques. In CHH group, plaque smooth muscle cells and collagen contents decreased, while plaque macrophages and lipids contents increased significantly (p<0.001). The contents of CD31 (p=0.0379) and endomucin (p=0.0196) in the plaque was higher in the CHH group and correlated with angiogenesis progression. Further, the content of monocyte chemotactic protein-1 (p=0.0376) and matrix metalloproteinase-2 was significantly higher (p=0.0212) in the CHH group. Conclusions: CHH may accelerate atherosclerosis progression in ApoE-/- mice by promoting angiogenesis and inflammation.

Accumulated exposure to high non-high-density lipoprotein cholesterol increases the risk of cardiovascular diseases in hypertensive individuals: An 11-year prospective cohort study.

BACKGROUND: The relationship of cumulative non high-density lipoprotein-cholesterol (Cum-non-HDL-C) concentration with the risk of cardiovascular disease (CVD) in individuals with hypertension remains unclear. METHODS: In total 27 234 participants for whom three consecutive total cholesterol and HDL-C concentrations were available, and who did not have CVD, comprising 13 617 with hypertension and 13 617 without from 2006 to 2010. Participants were placed into four groups according to Cum-non-HDL-C. Cox proportional hazards models were used to evaluate the relationship between Cum-non-HDL-C and the risk of CVD. RESULTS: Over a median 11 years, 1,298 participants with hypertension developed CVD. After adjustment for multiple potential confounding factors, compared with participants with hypertension and Cum-non-HDL-C < 130 mg/dl, the fully adjusted hazard ratios and 95% confidence intervals of CVD associated with Cum-non-HDL-C values of 130-159 mg/dl, 160-189 mg/dl, and ≥ 190 mg/dl were 1.23 (1.01, 1.34), 1.27 (1.04, 1.56), and 1.51 (1.13, 2.01), respectively. Compared with participants without hypertension and a Cum-non-HDL-C < 130 mg/dl, the fully adjusted hazard ratios (95% confidence intervals) for the participants with hypertension and Cum-non-HDL-Cs < 130 mg/dl, 130-159 mg/dl, 160-189 mg/dl, and ≥ 190 mg/dl were 1.84 (1.55, 2.18), 2.16 (1.81, 2.59), 2.17 (1.73, 2.70), and 2.45 (1.12, 3.29), respectively. CONCLUSIONS: A consistently high non-HDL-C concentration increases the risk of CVD in individuals with hypertension, as does prolonged exposure to a high non-HDL-C concentration. Thus, the achievement of target blood pressure and non-HDL-C concentrations should help reduce the risk of CVD in individuals with hypertension.

Effect of Aerobic Exercise on Arterial Stiffness in Individuals with Different Smoking Statuses.

This study aimed to investigate the immediate effects of acute bout of aerobic exercise on arterial stiffness in individuals with different smoking statuses. A total of 940 male individuals (mean age of 36.82±7.76 years) in the Kailuan study cohort were selected to participate in the fifth National Physical Fitness Monitoring. All participants completed measurements of brachial - ankle pulse wave velocity (baPWV) before and after twice-quantitative cycle ergometer exercise. Four groups were defined: (1) non-smokers (n=231), (2) former smokers (n=165), (3) light smokers (1-10 cigarettes/day, n=254), (4) heavy smokers (>10 cigarettes/day, n=290). Generalized linear models were established to analyze between-group differences in the change in baPWV before and after acute aerobic exercise in individuals with different smoking statuses. Overall, after acute aerobic exercise, baPWV was immediately decreased significantly (-33.55 cm/s [95% CI, - 39.69 to -27.42]). Compared with non-smokers, former smokers, light smokers, and heavy smokers showed a greater decrease in baPWV (-12.17 cm/s [95%CI, - 30.08 to 5.75], - 18.43 cm/s [95%CI, -34.69 to - 2.16], and -22.46 cm/s [95%CI, - 38.39 to - 6.54]) respectively. There is a transient decrease in baPWV in individuals with different smoking statuses. Compared with non-smokers, baPWV decreased more significantly in light and heavy smokers.

Age-dependent changes in the risk of weight gain in Chinese adults: results from the Kailuan cohort study.

OBJECTIVES: Over the past decades, China has seen a dramatic epidemic of overweight and obesity. However, the optimal period for interventions to prevent overweight/obesity in adulthood remains unclear, and little is known regarding the joint effect of sociodemographic factors on weight gain. We aimed to investigate the associations of weight gain with sociodemographic factors, including age, sex, educational level, and income. STUDY DESIGN: This was a longitudinal cohort study. METHODS: This study included 121,865 participants aged 18-74 years from the Kailuan study who attended health examinations over the period 2006-2019. Multivariate logistic regression and restricted cubic spline were used to evaluate the associations of sociodemographic factors with body mass index (BMI) category transitions over two, six, and 10 years. RESULTS: In the analysis of 10-year BMI changes, the youngest age group had the highest risks of shifting to higher BMI categories, with odds ratio of 2.42 (95% confidence interval 2.12-2.77) for a transition from underweight or normal weight to overweight or obesity and 2.85 (95% confidence interval 2.17-3.75) for a transition from overweight to obesity. Compared with baseline age, education level was less related to these changes, whereas gender and income were not significantly associated with these transitions. Restricted cubic spline analyses suggested reverse J-shaped associations of age with these transitions. CONCLUSIONS: The risk of weight gain in Chinese adults is age dependent, and clear public healthcare messaging is needed for young adults who are at the highest risk of weight gain.

Remnant Cholesterol Variability and Incident Ischemic Stroke in the General Population.

BACKGROUND: Studies have demonstrated that remnant cholesterol is correlated with the risk of ischemic stroke. However, it is unknown whether visit-to-visit variability in remnant cholesterol concentration affects ischemic stroke. We sought to examine the role of remnant cholesterol variability in the subsequent development of ischemic stroke in the general population. METHODS: We performed a post hoc analysis including eligible participants from the Kailuan Study cohort who underwent 3 health examinations and were free of atrial fibrillation, myocardial infarction, stroke, cancer, or known lipid-medication use from 2006 to 2010. Participants were followed up until the end of 2017. Variability was quantified as variability independent of the mean, average real variability, and SD. Multivariate analysis was performed using the Fine and Gray competing risk model to estimate subhazard ratios assuming death as a competing risk. RESULTS: The final study cohort comprised 38 556 participants. After a median follow-up of 7.0 years, 1058 individuals were newly diagnosed with ischemic stroke. After adjusting for age (time scale), sex, smoking status, alcohol consumption, physical activity, hypertension, diabetes, family history of cardiovascular disease, body mass index, estimated glomerular filtration rate, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and mean remnant cholesterol, the highest quartile (quartile 4) of variability independent of the mean of remnant cholesterol was associated with an increased ischemic stroke risk compared with the lowest quartile (quartile 1), (subhazard ratio, 1.27 [95% CI, 1.06-1.53]). For each 1-SD increase in variability independent of the mean of remnant cholesterol, the risk increased by 9% (subhazard ratio, 1.09 [95% CI, 1.03-1.16]). The association was also significant using average real variability and SD as indices of variability. CONCLUSIONS: Greater remnant cholesterol variability was associated with a higher risk of ischemic stroke in the general population.

Triglyceride-glucose index trajectory and stroke incidence in patients with hypertension: a prospective cohort study.

BACKGROUND: It has been suggested that the baseline triglyceride-glucose (TyG) index, a simple surrogate measure for insulin resistance, is significantly associated with the occurrence of stroke. Nevertheless, the impact of longitudinal patterns of TyG on the stroke risk in hypertensive patients is still unknown. Hence, this study aimed to investigate the association between TyG index trajectory and stroke risk among hypertensive patients. METHODS: This prospective study included 19,924 hypertensive patients from the Kailuan Study who underwent three waves survey and were free of myocardial infarction, cancer and stroke before or during 2010. The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2], and latent mixed modelling was used to identify the trajectory of TyG during the exposure period (2006-2010). Furthermore, the Cox proportional hazard models were applied to estimate the hazard ratio (HR) and 95% confidence interval (CI) for incident stroke of different trajectory groups. RESULTS: Five distinct TyG trajectory were identified during 2006-2010: low-stable (n = 2483; range, 8.03-8.06), moderate low-stable (n = 9666; range, 8.58-8.57), moderate high-stable (n = 5759; range, 9.16-9.09), elevated-stable (n = 1741; range, 9.79-9.75), and elevated-increasing (n = 275; range, 10.38-10.81). During the median follow-up of 9.97 years, 1,519 cases of incident stroke were identified, including 1,351 with ischemic stroke and 215 with hemorrhage stroke. After adjusting for confounding variables, the HR and 95% CI of stroke were 2.21 (1.49,3.28) for the elevated-increasing group, 1.43 (1.13,1.83) for the elevated-stable group, 1.35 (1.10,1.64) for the moderate high-stable group, 1.26 (1.06,1.52) for the moderate low-stable group, respectively, when compare with the low-stable group. Similar results were observed in ischemic stroke, but a significant association was not found between TyG trajectory and risk of hemorrhage stroke. CONCLUSION: A long-term elevated TyG index in hypertensive patients is associated with an increased risk of stroke, especially ischemic stroke. This finding implies that regular monitoring of TyG index may assist in identifying individuals at a higher risk of stroke among patients with hypertension.

NPY promotes macrophage migration by upregulating matrix metalloproteinase-8 expression.

Macrophage migration is thought to participate in obesity-related cardiovascular diseases. Matrix metalloproteinase-8 (MMP-8) possesses proteolytic activity on the extracellular matrix (ECM), which promotes macrophage migration to the site of vascular injury. Neuropeptide Y (NPY) is a bioactive peptide involved in MMP expression. However, it is uncertain whether NPY can regulate the expression of matrix metalloproteinase-8 (MMP-8) in macrophages. In this study, wild-type C57BL/6 and NPY-/- mice were fed a high-fat diet and subjected to subcutaneous carotid artery injury with ferric chloride, to observe the role of NPY and macrophages in neointima formation. In addition, Raw264.7 cells were treated with NPY and its antagonists to observe MMP-8 expression and macrophage migration. We found that NPY-/- mice exhibited significantly reduced neointima formation after carotid artery injury. The content of macrophages and MMP-8 in the neointima and media were also significantly reduced in NPY-/- mice compared with C57BL/6 mice. Moreover, the expression of MMP-8 in macrophages was also decreased in NPY-/- mice. NPY increased MMP-8 messenger RNA and protein expression in Raw264.7 cells in vitro, and this effect was abrogated by the Y1R antagonist. In addition, NPY increased the phosphorylation of ERK1/2, which was significantly attenuated by co-treatment with the Y1R antagonist. Moreover, NPY-induced MMP-8 expression could be decreased by the ERK1/2 inhibitor PD98059. Furthermore, NPY promoted macrophage migration across type I collagen in vitro. In conclusion, NPY promotes macrophage migration by upregulating MMP-8 expression, which we believe to be an underappreciated mechanism of the increased progression of neointima formation.

Ubiquitin-Specific Protease 22/Silent Information Regulator 1 Axis Plays a Pivotal Role in the Prognosis and 5-Fluorouracil Resistance in Hepatocellular Carcinoma.

BACKGROUND: Ubiquitin-specific protease 22 (USP22) is described as a key subunit of the Spt-Ada-Gcn5 acetyl transferase complex, which plays an important role in the prognosis and resistance to chemotherapy drugs in hepatocellular carcinoma (HCC). Silent information regulator 1 (SIRT1) is a member of the sirtuin family that is deubiquitinated by USP22. However, it is still unknown whether USP22 and SIRT1 co-expression is associated with disease progression and 5-Fluorouracil (5-FU) resistance in HCC. METHODS: 141 patients who received hepatectomy at our hospital from January 2010 to December 2014 were enrolled in this study. The expression of USP22 and SIRT1 was detected by immunohistochemical staining. Clinicopathological features, including age, gender, tumor number, tumor size, tumor differentiation, tumor stage, alpha-fetoprotein and microscopic vascular invasion, were assessed. Further experiments confirmed the role of SIRT1 in 5-FU drug resistance in vivo. RESULTS: Immunohistochemical staining showed that the high expression of USP22 and SIRT1 was frequently observed in HCC tissues relative to normal liver tissues. Overexpression of USP22 is associated with microscopic vascular invasion (MVI). Further analysis showed that the co-expression of USP22 and SIRT1 was more effective in predicting the prognosis of HCC. The SIRT1 inhibitor EX-527 dramatically inhibited the expression of Cyclin B1 and resistance-associated protein 3 (MRP3) to reduce 5-FU drug resistance in vivo. CONCLUSION: These findings suggest that the co-expression of USP22 and SIRT1 is significantly associated with unfavorable HCC progression. The inhibition of SIRT1 in vivo could be valuable in improving 5-FU drug sensitivity and inhibiting tumor cell proliferation and inducing apoptosis.

Prolonged hyperlipidemia exposure increases the risk of arterial stiffness in young adults: a cross-sectional study in a cohort of Chinese.

BACKGROUND: Hyperlipidemia is associated with arterial stiffness. Herein, We examined the effect of prolonged exposure to hyperlipidemia on the risk of arterial stiffness in young adults. METHODS: A study cohort (35-55 years old) that received health check-ups in the Kailuan study (2014-2016) were assessed. Hyperlipidemia was defined as a low-density lipoprotein cholesterol ≥160 mg/dL according to the Chinese Guidelines for the Management of Dyslipidemia in Adults. Subjects were divided into three groups based on the number of years with hyperlipidemia: normal (0 years), low exposure (1-5 years), and high exposure (5-10 years) groups. Arterial stiffness was defined as brachial-ankle pulse wave velocity > 1400 cm/s. For all subjects and subjects that did not meet statin treatment criteria under guidelines, logistics regression was used to analyze the effect of prolonged hyperlipidemia exposure on arterial stiffness in different age groups. RESULTS: Among 12,431 subjects, the mean age was 46.42 ± 5.34 years with 9000 men (72.4%). Brachial-ankle pulse wave velocity gradually increased with increased exposure duration. Logistic regression analysis showed that hyperlipidemia exposure was a risk factor for arterial stiffness in the low (1.22 times) and high (1.49 times) exposure groups compared with the normal group. In the different age groups, the risk of arterial stiffness increased with the duration of hyperlipidemia exposure, apart for the 35-40-year-old population. The effect of hyperlipidemia exposure duration on arterial stiffness in young adults that did not meet statin treatment criteria under guidelines was similar to the general population. CONCLUSIONS: Prolonged exposure to hyperlipidemia in young adults increases the risk of arterial stiffness. Young adults with this condition may benefit from more aggressive primary prevention. TRIAL REGISTRATION: Name of the registry: Risk factors and intervention for cardiology, cerebrovascular and related disease (Kailuan Study) Trial registration number: CHiCTR-TNC1100 1489 Date of registration: Aug 24, 2011 URL of trial registry record: http://www.chictr.org.cn/showproj.aspx?proj=8050.

C7-Prenylation of Tryptophan-Containing Cyclic Dipeptides by 7-Dimethylallyl Tryptophan Synthase Significantly Increases the Anticancer and Antimicrobial Activities.

Prenylated natural products have interesting pharmacological properties and prenylation reactions play crucial roles in controlling the activities of biomolecules. They are difficult to synthesize chemically, but enzymatic synthesis production is a desirable pathway. Cyclic dipeptide prenyltransferase catalyzes the regioselective Friedel-Crafts alkylation of tryptophan-containing cyclic dipeptides. This class of enzymes, which belongs to the dimethylallyl tryptophan synthase superfamily, is known to be flexible to aromatic prenyl receptors, while mostly retaining its typical regioselectivity. In this study, seven tryptophan-containing cyclic dipeptides 1a-7a were converted to their C7-regularly prenylated derivatives 1b-7b in the presence of dimethylallyl diphosphate (DMAPP) by using the purified 7-dimethylallyl tryptophan synthase (7-DMATS) as catalyst. The HPLC analysis of the incubation mixture and the NMR analysis of the separated products showed that the stereochemical structure of the substrate had a great influence on their acceptance by 7-DMATS. Determination of the kinetic parameters proved that cyclo-l-Trp-Gly (1a) consisting of a tryptophanyl and glycine was accepted as the best substrate with a KM value of 169.7 µM and a turnover number of 0.1307 s-1. Furthermore, docking studies simulated the prenyl transfer reaction of 7-DMATS and it could be concluded that the highest affinity between 7-DMATS and 1a. Preliminary results have been clearly shown that prenylation at C7 led to a significant increase of the anticancer and antimicrobial activities of the prenylated derivatives 1b-7b in all the activity test experiment, especially the prenylated product 4b.

Association Between Body Mass Index (BMI) and Brachial-Ankle Pulse Wave Velocity (baPWV) in Males with Hypertension: A Community-Based Cross-Section Study in North China.

BACKGROUND The aim of this study was to investigate the association between body mass index (BMI) and brachial-ankle pulse wave velocity (baPWV) in hypertensive males. MATERIAL AND METHODS Altogether, 14 866 male hypertensive participants were included in the analysis. Participants were divided into 3 groups: low BMI group (BMI <24 kg/m²), moderate BMI group (24 kg/m² ≤BMI <28 kg/m²), and high BMI group (BMI ≥28 kg/m²). According to baPWV values, arteriosclerosis (AS) was set as 3 degrees: mild AS (baPWV ≥1400 cm/s), moderate AS (baPWV ≥1700 cm/s) and severe AS (baPWV ≥2000 cm/s). Multivariate logistic regression analysis was used to explore the effect of different BMI groups on different degrees of AS. The multivariate linear regression analysis was used to explore the relationship between BMI and baPWV. RESULTS Among low BMI, moderate BMI, and high BMI groups, the average baPWV values were 1824±401 cm/s, 1758±363 cm/s, and 1686±341 cm/s, respectively. Prevalence in the mild, moderate and high BMI groups were 91.0%, 87.8%, 81.5%, respectively for mild AS; 55.3%, 48.8%, and 40.0% respectively for moderate AS; and 25.9%, 20.2%, and 14.9% respectively for severe AS. Compared to the low BMI group, multivariate logistic regression analysis showed that odds ratio (OR) and 95% confidence intervals (95%CI) in the moderate BMI group and the high BMI were 0.71 (95%Cl, 0.62-0.80), 0.43 (95%Cl, 0.38-0.50) for mild AS; and similar trends were shown for moderate AS and severe AS. Based on age-stratification, a negative relationship remained for 35-55 years old participants for different degrees of AS among the moderate BMI group and the high BMI group. A negative relationship was detected between BMI and baPWV in total and different age-stages. CONCLUSIONS Among male hypertension participants in this study, there was a negative relationship between BMI and baPWV. High BMI was found to be a protective factor for AS especially in the age range of 35-55 years.

Nitrogenase-mimic iron-containing chalcogels for photochemical reduction of dinitrogen to ammonia.

A nitrogenase-inspired biomimetic chalcogel system comprising double-cubane [Mo2Fe6S8(SPh)3] and single-cubane (Fe4S4) biomimetic clusters demonstrates photocatalytic N2 fixation and conversion to NH3 in ambient temperature and pressure conditions. Replacing the Fe4S4 clusters in this system with other inert ions such as Sb(3+), Sn(4+), Zn(2+) also gave chalcogels that were photocatalytically active. Finally, molybdenum-free chalcogels containing only Fe4S4 clusters are also capable of accomplishing the N2 fixation reaction with even higher efficiency than their Mo2Fe6S8(SPh)3-containing counterparts. Our results suggest that redox-active iron-sulfide-containing materials can activate the N2 molecule upon visible light excitation, which can be reduced all of the way to NH3 using protons and sacrificial electrons in aqueous solution. Evidently, whereas the Mo2Fe6S8(SPh)3 is capable of N2 fixation, Mo itself is not necessary to carry out this process. The initial binding of N2 with chalcogels under illumination was observed with in situ diffuse-reflectance Fourier transform infrared spectroscopy (DRIFTS). (15)N2 isotope experiments confirm that the generated NH3 derives from N2 Density functional theory (DFT) electronic structure calculations suggest that the N2 binding is thermodynamically favorable only with the highly reduced active clusters. The results reported herein contribute to ongoing efforts of mimicking nitrogenase in fixing nitrogen and point to a promising path in developing catalysts for the reduction of N2 under ambient conditions.