Design, synthesis and anticancer evaluation of novel half-sandwich Ru(II) complexes bearing pyrazalone moiety: Apoptosis inducers based on mitochondrial dysfunction and G0/G1 arrest.

Six half-sandwich Ru(II) complexes (Ru1-Ru6), integrated with 5-phenyl-2-(pyridin-2-yl)-2,4-dihydro-3H-pyrazol-3-one (PDPO1-PDPO6) ligands, were synthesized and spectroscopically characterized. The structure of Ru3 that crystallized as a monoclinic crystal with P21/c space group was further confirmed by X-ray single crystal diffraction. Prototropic tautomerism within the complexes transformed OH-form ligands to NH-form, forming a hydrogen bond (Cl1---H-N3). The complexes and ligands' cytotoxicity was assessed against several cancerous (HepG2, A549, MCF-7) and normal Vero cell lines. Relative to the ligands and Cisplatin, complexes (Ru2, Ru3, Ru5, Ru6) exhibited potent cytotoxicity against cancer cells, with IC50 values from 2.05 to 15.69 µM/L, excluding Ru1 and Ru4. Specifically, Ru2, Ru3, and Ru5 demonstrated superior anti-HepG2 properties. Compared to Cisplatin, Ru2 and Ru5 were less toxic to Vero cells, highlighting their enhanced selectivity in toxicity. Structure-activity relationship (SAR) studies indicated that t-butyl substitution (in Ru2) or -Cl (in Ru5) on the benzene ring significantly improved the selective toxicity. These complexes manifested substantial lipophilicity, cellular uptake, and were quickly hydrolyzed to Ru-H2O species. Roughly positive correlations were observed between hydrolysis rate, lipophilicity, cellular uptake, and anticancer activities. Ru2, investigated specifically, induced apoptosis in HepG2 cells at concentrations of 10 and 20 µM/L through ROS-mediated mitochondrial dysfunction and G0/G1phase arrest, associated with altered P21, cyclin D, and CDK4 expression levels.

Positive association between alkaline phosphatase and arteriosclerosis: a cross-sectional study.

AIMS: Serum alkaline phosphatase (ALP) is known to be associated with cardiovascular events and cerebral arteriosclerosis. However, the link between ALP and early arteriosclerosis remains unclear. This study investigated the relationship between ALP and early arteriosclerosis assessed by brachial-ankle pulse wave velocity (Ba-PWV). METHODS: This retrospective analysis included 5011 participants who underwent health examinations, including ALP and Ba-PWV measurement, at the Second Hospital of Hebei Medical University from 2012 to 2017. Regression analysis, smoothing function analysis in the generalized additive model (GAM), threshold effect analysis, and subgroup analyses were performed. RESULTS: Multivariate regression analysis identified a significantly positive association between serum ALP and arteriosclerosis [odds ratio (OR) = 1.008, 95% confidence interval (CI) 1.004-1.011, P  < 0.001]. Smoothing function analysis indicated a two-stage association between ALP and arteriosclerosis. Furthermore, threshold effect analysis determined an inflection point at 135 U/l, below which the relationship was linearly positive and above which the risk of arteriosclerosis did not increase prominently with increasing ALP (OR = 1.009, 95% CI: 1.005-1.013, P  < 0.001; OR = 0.976, 95% CI: 0.952-1.002, P  = 0.068). However, ALP was not associated with arteriosclerosis only in participants with diabetes (OR = 0.996, 95% CI: 0.979-1.014, P  = 0.690). A positive association between Ba-PWV and arteriosclerosis was observed for both the arteriosclerosis and nonarteriosclerosis groups ( ß â€Š= 9.10, 95% CI: 4.67-13.54, P  < 0.001; ß â€Š= 8.02, 95% CI: 5.67-10.37, P  < 0.001). CONCLUSION: In this study, the serum ALP level was positively associated with early arteriosclerosis, with a saturation effect beyond ALP = 135 U/l. However, the positive association between ALP and arteriosclerosis was unclear in adults with diabetes.

Continuous Positive Linear Association between the Monocyte to High-Density Lipoprotein Cholesterol Ratio and Hypertension: A Cross-Sectional Study.

Background: Hypertension poses a major threat to human health, and inflammation is associated with hypertension. The monocyte to high-density lipoprotein cholesterol ratio (MHR) represents a new inflammatory indicator. However, the relationship between the MHR and hypertension remains unclear. The present study investigated the association of MHR with hypertension. Method: For this cross-sectional study, we continuously collected data from the Physical Examination Centre of the Second Hospital of Hebei Medical University (N = 6632). The data included patients' demographic information and clinical information including blood pressure, blood biochemical measurements, and MHR. The relationship between the MHR and hypertension was examined using different methods in univariate and multivariate logistic analysis, smooth function analysis, the threshold saturation effect analysis and subgroup analysis. Results: The results showed that MHR was positively associated with hypertension without adjustment (odds ratio [OR] = 1.10, 95% confidence interval [CI]: 1.08-1.12, P < 0.001). The positive association still existed in minimally and fully adjusted models (OR = 1.08, 95% CI: 1.06-1.10, P < 0.001; OR = 1.07, 95% CI: 1.05-1.10, P < 0.001). Smooth function analysis of a generalized additive model revealed a continuous positive linear association between the MHR and hypertension throughout all MHR data (OR = 1.07, 95% CI: 1.05-1.10, P < 0.001). Subgroups analysis showed the homogeneity of the positive association among different subgroups. Conclusions: A continuous positive linear association was found between the MHR and hypertension in a health examination population.

Nonlinear relationship with saturation effect observed between neutrophil to high-density lipoprotein cholesterol ratio and atherosclerosis in a health examination population: a cross-sectional study.

BACKGROUND: The relationships between inflammatory indexes and atherosclerosis as well as those between blood lipid indexes and atherosclerosis have been widely studied, but the relationship between the neutrophil to high-density lipoprotein cholesterol ratio (NHR) and atherosclerosis had not been investigated until the present study. METHODS: For this cross-sectional study, we continuously collected data from a health examination population in the Second Hospital of Hebei Medical University from January 2012 to December 2017 (N = 1978). The collected data included clinical data, hematological indexes, and brachial-ankle pulse wave velocity (Ba-PWV). Atherosclerosis was defined as Ba-PWV ≥ 1400 cm/s. The relationship between the NHR and atherosclerosis was explored via univariate regression analysis, multivariate regression analysis, smoothing function analysis, and analysis of a threshold saturation effect. RESULTS: Among 1978 participants, the mean age was 54 years, 1189 participants (60.11%) were male, and 1103 (55.76%) had a history of atherosclerosis. Univariate analysis showed a positive association between the NHR and atherosclerosis [odds ratio (OR) = 1.19, 95% confidence interval (CI): 1.11-1.27, P < 0.01], and this positive association remained significant on multivariate analyses with adjustments for confounding factors (OR = 1.14, 95% CI: 1.06-1.24, P < 0.01). Generalized additive model results revealed a non-linear relationship with a saturation effect between the NHR and atherosclerosis, with a threshold at 3.32. At values ≤ 3.32, the NHR was positively associated with atherosclerosis, but the association was not statistically significant for values > 3.32. CONCLUSION: A nonlinear relationship with a certain saturation effect was observed between the NHR and atherosclerosis in a health examination population.

Simple renal cyst as an independent risk factor for hypertension.

A simple renal cyst (SRC) may increase the risk for hypertension. The authors examined the relationship between a SRC and hypertension in participants receiving physical examinations at Hebei Medical University. This study enrolled 66 883 participants who received physical examinations at our center from January 2012 to December 2017. Demographic data, medical history related to hypertension, hematological indexes, hypertension, and SRC subtype based on ultrasound examinations were examined. The relationship between SRC and hypertension was analyzed using univariate and multivariate logistic regression analysis in different models. Subgroup analysis and propensity score (PS) matching were also performed. Based on SRC subtype (unitary vs. multiple, small vs. large, unilateral vs. bilateral), a comprehensive scoring system was established to determine the effect of SRC load on hypertension. The results of univariate and multivariate analysis indicated that SRC was a risk factor for hypertension (P < .01). Subgroup and interaction analysis showed the homogeneity that SRC was an independent risk factor for hypertension in multiple subgroups (P > .05). A SRC remained an independent risk factor for hypertension after PS matching (P < .01). Based on a scoring system that considered different SRC subtypes, the risk for hypertension increased with renal cyst load (P < .01). In conclusions, a SRC was an independent risk factor for hypertension, and there was a positive correlation between SRC load and hypertension. The risk of hypertension increased gradually with the size, number, and location of a SRC. Careful follow-up or excision should be considered for patients with SRCs.

The Monocyte to High-Density Lipoprotein Cholesterol Ratio in the Prediction for Atherosclerosis: A Retrospective Study in Adult Chinese Participants.

The ratio of monocyte to high-density lipoprotein cholesterol level (MHR) was a newly proposed inflammatory and oxidative stress marker. This study aimed to explore the association between MHR and Brachial-ankle pulse wave velocity (Ba-PWV) in adult Chinese participants. A total of 2029 participants were divided into two groups according to the Ba-PWV: a high Ba-PWV group (Ba-PWV ≥1400 cm/s) and a low Ba-PWV group (Ba-PWV < 1400 cm/s). According to the cut-off points of quartile of MHR, the participants were divided into four groups. The relationship between MHR and Ba-PWV was analyzed. After adjusting for potential confounders, a non-linear relationship between MHR and Ba-PWV was found in the participants, and the inflection point was 7.78 in the non-linear curve. On the left of the inflection point, MHR had a positive correlation with Ba-PWV (OR = 1.17, 95% confidence interval (CI): 1.08 to 1.28, p < 0.01). However, there was no obvious relationship between MHR and Ba-PWV on the right of the inflection point (OR = 0.96, 95% CI: 0.90 to 1.01, p = 0.117). Further demographic analysis demonstrated that the positive relationship between MHR and Ba-PWV was found in the female participants with hypertension family history, but without a current history of hypertension, smoking, or drinking (p < 0.05). An increased MHR is a risk factor of atherosclerosis, which may predict the potential development of atherosclerosis. When the MHR is close to 7.78, it has the highest predictive value for the risk of atherosclerosis occurrence.

Updated hypertension prevalence, awareness, and control rates based on the 2017ACC/AHA high blood pressure guideline.

In 2017, the American College of Cardiology/American Heart Association (ACC/AHA) updated the Guideline of Prevention, Detection, Evaluation and Management and Management of High Blood Pressure (HBP) in Adults. The purpose of the current study was to evaluate the potential impact of the 2017ACC/AHA HBP guideline on hypertension prevalence, awareness, and control rates. The data were collected from Physical Examination Center of the Second Hospital of Hebei Medical University from January 2012 to December 2017 (N = 66 977), including demographic information and risk factors of hypertension. The hypertension prevalence, awareness, and control rates of people were evaluated according to the new guideline. Additionally, the factors related to hypertension prevalence were also assessed. According to previous HBP guideline, hypertension prevalence, awareness, and control rate were 30.54%, 44.33%, and 13.04%, respectively. However, when the 2017 ACC/AHA HBP guideline was introduced, the population with hypertension increased from 20 453 to 34 460, the hypertension prevalence rate increased from 30.54% to 51.45%, the awareness rate decreased from 44.33% to 26.31%, and the control rate declined from 13.04% to 2.72%. The most newly diagnosed hypertension patients were from the low-risk population with young age and without the above histories. The 2017ACC/AHA HBP guideline indicated that high hypertension prevalence rate still existed with a substantial increase, while the awareness and control rates were relatively lowered.