Development of hypertension models for lung cancer screening cohorts using clinical and thoracic aorta imaging factors.

This study aims to develop and validate nomogram models utilizing clinical and thoracic aorta imaging factors to assess the risk of hypertension for lung cancer screening cohorts. We included 804 patients and collected baseline clinical data, biochemical indicators, coexisting conditions, and thoracic aorta factors. Patients were randomly divided into a training set (70%) and a validation set (30%). In the training set, variance, t-test/Mann-Whitney U-test and standard least absolute shrinkage and selection operator were used to select thoracic aorta imaging features for constructing the AIScore. Multivariate logistic backward stepwise regression was utilized to analyze the influencing factors of hypertension. Five prediction models (named AIMeasure model, BasicClinical model, TotalClinical model, AIBasicClinical model, AITotalClinical model) were constructed for practical clinical use, tailored to different data scenarios. Additionally, the performance of the models was evaluated using receiver operating characteristic (ROC) curves, calibration curves and decision curve analyses (DCA). The areas under the ROC curve for the five models were 0.73, 0.77, 0.83, 0.78, 0.84 in the training set, and 0.77, 0.78, 0.81, 0.78, 0.82 in the validation set, respectively. Furthermore, the calibration curves and DCAs of both sets performed well on accuracy and clinical practicality. The nomogram models for hypertension risk prediction demonstrate good predictive capability and clinical utility. These models can serve as effective tools for assessing hypertension risk, enabling timely non-pharmacological interventions to preempt or delay the future onset of hypertension.

The effects of palliative care on patients with different classes heart function: A pilot study.

The aim of this study was to explore effects of palliative care (PC) on patients with different heart function. Patients with NYHA (New York Heart Association) class II, III, IV were divided into separate groups. The KCCQ (Kansas City Cardiomyopathy Questionnaire) and HADS (Hospital Anxiety and Depression Scale) scores were compared before and 3 months after PC intervention. After 3 months, compared with the control group, PC could further significantly improve the KCCQ, HADS-depression and -anxiety scores of patients in NYHA class IV (P < 0.05); PC could significantly improve the HADS-depression and -anxiety scores of patients with NYHA class III (P < 0.05), and had an improvement tendency on KCCQ score. The study revealed that PC can significantly improve anxiety and depression of patients with NYHA class III or IV, and significantly improve the quality of life of patients with NYHA class IV, but had no effects on patients with NYHA class II.

Associations of serum calcium/magnesium ratios with coronary artery disease in diabetes: a cross-sectional study.

OBJECTIVE: The early detection of coronary artery disease (CAD) in diabetes mellitus is a major clinical difficulty. The purpose of this paper is to find out a convenient and economical index to help to screen for patients with CAD in diabetes mellitus. METHOD: From January 2019 to December 2019, a total of 1028 patients hospitalized in the general department of our hospital have been enrolled in our cross-sectional study, of which 190 were diagnosed with CAD and 314 with diabetes. Differences of various factors between the CAD group and the non-CAD group were analyzed. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to evaluate the efficacy of each factor in predicting CAD. The correlation between calcium/magnesium (Ca/Mg) ratio and the prevalence of CAD in diabetic and non-diabetic people was compared, and the cutoff of Ca/Mg ratio to predict the risk of CAD in diabetic patients was calculated. RESULTS: Logistic regression analysis showed that serum high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, calcium, magnesium, Ca/Mg ratio, hypertension, diabetes, and smoking history were all associated with CAD. Among them, the AUC value of Ca/Mg ratio was the highest of 0.70. Furthermore, in diabetes patients, the AUC value of Ca/Mg ratio to predict the risk of CAD was 0.72, the cutoff was 2.55, the sensitivity was 77.1%, and the specificity was 53.7%. The prevalence rate of CAD was 18.5% below the cutoff, 46.9% higher than the cutoff, and the prevalence rate increased by 153.5%. CONCLUSION: The Ca/Mg ratio is a good predictor of the risk of CAD in diabetes, higher than the cutoff, the prevalence rate was significantly increased.PLA IN LANGUAGE SUMMARYCAD brings great pain and burden to patient. However, CAD is asymptomatic in quiet a few cases of type 2 diabetes until myocardial infarction or sudden cardiac death occurs. In this study, we explored the association between CAD and various serum factor. We found that the Ca/Mg ratio is of excellent value in screening CAD, especially in diabetes. Moreover, we found that the cutoff of Ca/Mg ratio was 2.55 in diabetic population and the prevalence rate of CAD was 18.5% below the cutoff, 46.9% higher than the cutoff. The Ca/Mg ratio will provide good prediction of the risk of CAD and make early detection easier in diabetes.

Opportunistic osteoporosis screening using chest CT with artificial intelligence.

Osteoporosis has a high incidence and a low detection rate. If it is not detected in time, it will cause osteoporotic fracture and other serious consequences. This study showed that the attenuation values of vertebrae on chest CT could be used for opportunistic screening of osteoporosis. This will be beneficial to improve the detection rate of osteoporosis and reduce the incidence of adverse events caused by osteoporosis. INTRODUCTION: To explore the value of the attenuation values of all thoracic vertebrae and the first lumbar vertebra measured by artificial intelligence on non-enhanced chest CT to do osteoporosis screening. METHODS: On base of images of chest CT, using artificial intelligence (AI) to measure the attenuation values (HU) of all thoracic and the first vertebrae of patients who underwent CT examination for lung cancer screening and dual-energy X-ray absorptiometry (DXA) examination during the same period. The patients were divided into three groups: normal group, osteopenia group, and osteoporosis group according to the results of DXA. Clinical baseline data and attenuation values were compared among the three groups. The correlation between attenuation values and BMD values was analyzed, and the predictive ability and diagnostic efficacy of attenuation values of thoracic and first lumbar vertebrae on osteopenia or osteoporosis risk were further evaluated. RESULTS: CT values of each thoracic vertebrae and the first lumbar vertebrae decreased with age, especially in menopausal women and presented high predictive ability and diagnostic efficacy for osteopenia or osteoporosis. After clinical data correction, with every 10 HU increase of CT values, the risk of osteopenia or osteoporosis decreased by 32 ~ 44% and 61 ~ 80%, respectively. And the combined diagnostic efficacy of all thoracic vertebrae was higher than that of a single vertebra. The AUC of recognizing osteopenia or osteoporosis from normal group was 0.831and 0.972, respectively. CONCLUSIONS: The routine chest CT with AI is of great value in opportunistic screening for osteopenia or osteoporosis, which can quickly screen the population at high risk of osteoporosis without increasing radiation dose, thus reducing the incidence of osteoporotic fracture.

Redd1 knockdown prevents doxorubicin-induced cardiac senescence.

Regulated in development and DNA damage response-1 (Redd1) is a stress-response gene that is transcriptionally induced by diverse stressful stimuli to influence cellular growth and survival. Although evidence suggests that aging may drive Redd1 expression in skeletal muscles, the expression patterns and functions of Redd1 in senescent cardiomyocytes remain unspecified. To address this issue, in vitro and in vivo models of cardiomyocyte senescence were established by administration of doxorubicin (Dox). Redd1 overexpression and knockdown was achieved in cultured H9c2 cardiomyocytes and mouse tissues using, respectively, lentivirals and adeno-associated virus 9 (AAV9) vectors. In the hearts of both aged (24 months old) and Dox-treated mice, as well as in Dox-exposed H9c2 cardiomyocytes, high Redd1 expression accompanied the increase in both cellular senescence markers (p16INK4a and p21) and pro-inflammatory cytokine expression indicative of a stress-associated secretory phenotype (SASP). Notably, Redd1 overexpression accentuated, whereas Redd1 silencing markedly attenuated, Dox-induced cardiomyocyte senescence features both in vitro and in vivo. Notably, AAV9-shRNA-mediated Redd1 silencing significantly alleviated Dox-induced cardiac dysfunction. Moreover, through pharmacological inhibition, immunofluorescence, and western blotting, signaling pathway analyses indicated that Redd1 promotes cardiomyocyte senescence as a downstream effector of p38 MAPK to promote NF-kB signaling via p65 phosphorylation and nuclear translocation.

MicroRNA-126 enhances the biological function of endothelial progenitor cells under oxidative stress via PI3K/Akt/GSK3ß and ERK1/2 signaling pathways.

Endothelial progenitor cell (EPC) transplantation is a safe and effective method to treat acute myocardial infarction (AMI). However, oxidative stress leads to the death of a large number of EPCs in the early stage of transplantation, severely weakening the therapeutic effect. Previous studies demonstrated that microRNAs regulate the biological function of EPCs. The aim of the current study was to investigate the effect of microRNA on the biological function of EPCs under oxidative stress. Quantitative reverse transcription PCR was performed to detect the expression of miR-126, miR-508-5p, miR-150, and miR-16 in EPCs from rats, among which miR-126 showed a relatively higher expression. Treatment with H2O2 decreased miR-126 expression in EPCs in a dose-dependent manner. EPCs were further transfected with miR-126 mimics or inhibitors, followed by H2O2 treatment. Overexpression of miR-126 enhanced the proliferation, migration, and tube formation of H2O2-treated EPCs. MiR-126 overexpression also inhibited reactive oxygen species and malondialdehyde levels and enhanced superoxide dismutase levels, as well as increased angiopoietin (Ang)1 expression and decreased Ang2 expression in H2O2-treated EPCs. Moreover, miR-126 participated in the regulation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase 3ß (GSK3ß) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in EPCs, where both pathways were activated after miR-126 overexpression in H2O2-treated EPCs. Overall, we showed that miR-126 promoted the biological function of EPCs under H2O2-induced oxidative stress by activating the PI3K/Akt/GSK3ß and ERK1/2 signaling pathway, which may serve as a new therapeutic approach to treat AMI.

Honokiol antagonizes doxorubicin­induced cardiomyocyte senescence by inhibiting TXNIP­mediated NLRP3 inflammasome activation.

Senescence of cardiomyocytes is considered a key factor for the occurrence of doxorubicin (Dox)­associated cardiomyopathy. The NOD­like receptor family pyrin domain­containing 3 (NLRP3) inflammasome is reported to be involved in the process of cellular senescence. Furthermore, thioredoxin­interactive protein (TXNIP) is required for NLRP3 inflammasome activation and is considered to be a key component in the regulation of the pathogenesis of senescence. Studies have demonstrated that pretreatment with honokiol (Hnk) can alleviate Dox­induced cardiotoxicity. However, the impact of Hnk on cardiomyocyte senescence elicited by Dox and the underlying mechanisms remain unclear. The present study demonstrated that Hnk was able to prevent Dox­induced senescence of H9c2 cardiomyocytes, indicated by decreased senescence­associated ß­galactosidase (SA­ß­gal) staining, as well as decreased expression of p16INK4A and p21. Hnk also inhibited TXNIP expression and NLRP3 inflammasome activation in Dox­stimulated H9c2 cardiomyocytes. When TXNIP expression was enforced by adenovirus­mediated gene overexpression, the NLRP3 inflammasome was activated, which led to inhibition of the anti­inflammation and anti­senescence effects of Hnk on H9c2 cardiomyocytes under Dox treatment. Furthermore, adenovirus­mediated TXNIP­silencing inhibited the NLRP3 inflammasome. Consistently, TXNIP knockdown enhanced the anti­inflammation and anti­senescence effects of Hnk on H9c2 cardiomyocytes under Dox stimulation. In summary, Hnk was found to be effective in protecting cardiomyocytes against Dox­stimulated senescence. This protective effect was mediated via the inhibition of TXNIP expression and the subsequent suppression of the NLRP3 inflammasome. These results demonstrated that Hnk may be of value as a cardioprotective drug by inhibiting cardiomyocyte senescence.

Redd1 protects against post­infarction cardiac dysfunction by targeting apoptosis and autophagy.

Post­infarction remodeling is accompanied and influenced by perturbations in the mammalian target of rapamycin (mTOR) signaling. Regulated in development and DNA damage response­1 (Redd1) has been reported to be involved in DNA repair and modulation of mTOR activity. However, little is known about the role of Redd1 in the heart. In the present study the potential contribution of Redd1 overexpression to the chronic phase of heart failure after myocardial infarction (MI) was explored and the mechanisms underlying Redd1 actions were determined. Redd1 was downregulated in the mouse heart subjected to MI surgery. To determine the role of Redd1 in the process of MI, adeno­associated virus 9 mediated overexpression of Redd1 was used to enhance Redd1 content in cardiomyocytes. Redd1 overexpression improved left ventricular dysfunction and reduced the expansion index. Additionally, Redd1 overexpression resulted in suppressed myocardial apoptosis and improved autophagy. Furthermore, the studies revealed that Redd1 overexpression could inhibit the phosphorylation of mTOR and its downstream effectors P70/S6 kinase and 4EBP1. In conclusion, this study demonstrated that Redd1 overexpression protects against the development and persistence of heart failure post MI by reducing apoptosis and enhancing autophagy via the mTOR signaling pathway. The present study clearly demonstrated that Redd1 is a therapeutic target in the development of heart failure after MI.

Reduced NRF2 expression suppresses endothelial progenitor cell function and induces senescence during aging.

Aging is associated with an increased risk of cardiovascular disease. Numerical and functional declines in endothelial progenitor cells (EPCs) limit their capacity for endothelial repair and promote the development of cardiovascular disease. We explored the effects of nuclear factor (erythroid-derived 2)-like 2 (NRF2) on EPC activity during aging. Both in vitro and in vivo, the biological functioning of EPCs decreased with aging. The expression of NRF2 and its target genes (Ho-1, Nqo-1 and Trx) also declined with aging, while Nod-like receptor protein 3 (NLRP3) expression increased. Aging was associated with oxidative stress, as evidenced by increased reactive oxygen species and malondialdehyde levels and reduced superoxide dismutase activity. Nrf2 silencing impaired the functioning of EPCs and induced oxidative stress in EPCs from young mice. On the other hand, NRF2 activation in EPCs from aged mice protected these cells against oxidative stress, ameliorated their biological dysfunction and downregulated the NLRP3 inflammasome. These findings suggest NRF2 can prevent the functional damage of EPCs and downregulate the NLRP3 inflammasome through NF-κB signaling.

Nrf2 protects against diabetic dysfunction of endothelial progenitor cells via regulating cell senescence.

Diabetes is associated with an increased risk of cardiovascular disease. A decrease in the number and functionality of endothelial progenitor cells (EPCs) leads to reduced endothelial repair and the development of cardiovascular disease. The aim of the present study was to explore the effect and underlying mechanisms of nuclear factor erythroid 2­related factor 2 (Nrf2) on EPC dysfunction caused by diabetic mellitus. The biological functions of EPCs in streptozotocin­induced diabetic mice were evaluated, including migration, proliferation, angiogenesis and the secretion of vascular endothelial growth factor (VEGF), stromal­derived growth factor (SDF) and nitric oxide (NO). Oxidative stress levels in diabetic EPCs were also assessed by detecting intracellular reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA). EPC senescence was evaluated by measuring p16 and b­gal expression and observing the senescence­associated secretory phenotype. In addition, the function of EPCs and level of oxidative stress were assessed following Nrf2 silencing or activation. Nrf2 silencing resulted in a decrease of EPC biological functions, accelerated cell senescence and increased oxidative stress, as indicated by ROS and MDA upregulation accompanied with decreased SOD activity. Furthermore, Nrf2 silencing inhibited migration, proliferation and secretion in EPCs, while it increased oxidative stress and cell senescence. Nrf2 activation protected diabetic EPCs against the effects of oxidative stress and cell senescence, ameliorating the biological dysfunction of EPCs derived from mice with diabetes. In conclusion, Nrf2 overexpression protected against oxidative stress­induced functional damage in EPCs derived from diabetic mice by regulating cell senescence.

Hypoxic Preconditioning Enhances Biological Function of Endothelial Progenitor Cells via Notch-Jagged1 Signaling Pathway.

BACKGROUND Hypoxic preconditioning may be a key influence on functions of endothelial progenitor cells (EPCs). MATERIAL AND METHODS To investigate the role and mechanism of the Notch-Jagged1 pathway on endothelial progenitor cells in hypoxic preconditioning, endothelial progenitor cells were randomly allocated into 5 groups: 1 Normoxic control group; 2 Hypoxic blank group; 3 Hypoxic+25 µM DAPT group; 4 Hypoxic+50 µM DAPT group; 5 Hypoxic+100 µM DAPT group. After reoxygenation, protein and mRNA levels of Jagged1 were measured by Western blot and quantitative RT-PCR. The MTT test was used to assess proliferation. ELISA was used to measure NO and VEGF secretion. RESULTS Hypoxic preconditioning treatment significantly upregulated both protein and mRNA levels of Jagged1 in endothelial progenitor cells. It also enhanced proliferation ability and elevated secretion of NO and VEGF. Furthermore, after blocking the Notch pathway by using DAPT, Jagged1 expression and EP proliferation, migration, and secretion of NO and VEGF were decreased in a dose-dependent manner. CONCLUSIONS Our results suggest the Notch-Jagged1 pathway enhances EPCs proliferation and secretion ability during hypoxic preconditioning.

Mechanisms underlying protective effects of trimetazidine on endothelial progenitor cells biological functions against H2O2-induced injury: involvement of antioxidation and Akt/eNOS signaling pathways.

Trimetazidine (TMZ) is a widely used drug exerting cardioprotective effects against ischemic heart disease through a number of mechanisms in conditions of oxidative stress. However, there are few data regarding the effects of TMZ on endothelial lineage, especially endothelial progenitor cells (EPCs). Thus, we sought to investigate whether TMZ could protect EPCs against oxidative stress injury induced by H2O2 (100 µM) and the preliminary mechanisms involved in vitro. The results showed that pretreatment of EPCs with TMZ (10 µM) protected the proliferation, adhesion, migration, and apoptosis of EPCs against H2O2, accompanied by an increase in superoxide dismutase (SOD) activity, a decrease in malonaldehyde (MDA) content, and increases in eNOS, Akt phosphorylation, and NO production. These TMZ-mediated beneficial effects on EPCs could be attenuated by pre-incubation with the Akt inhibitor triciribine. In conclusion, the present study demonstrates that TMZ ameliorated H2O2-induced impairment of biological functions in EPCs with the involvement of antioxidation and Akt/eNOS signaling pathway. These findings suggest that TMZ mediating preservation of EPCs may contribute to its cardioprotective effects on ischemic heart disease.

PTX3 is located at the membrane of late apoptotic macrophages and mediates the phagocytosis of macrophages.

Apoptotic macrophages are removed by neighboring phagocytes (efferocytosis), which is an important event in advanced atherosclerosis. Recent reports have elucidated some key molecular regulators in efferocytosis including complement C1q, MFGE8, and MERTK. However, it remains unknown whether the long pentraxin 3 (PTX3), which is an important molecule that is involved in apoptotic cell clearance in the immune response, plays a part in efferocytosis during advanced atherosclerosis. In this study, we modeled macrophage apoptosis in advanced plaques by incubating macrophages (peritoneal macrophages isolated from C57 mice) with free cholesterol (free cholesterol-induced apoptotic macrophages, FC-AMs). FC-AMs were added to a monolayer of fresh phagocytes to study the engulfment response. We observed that PTX3 was mainly located at the membrane of late apoptotic macrophages. The anti-PTX3 monoclonal Ab 16B5 inhibited the engulfment of late apoptotic macrophages by phagocytes in a dose-dependent manner (from 14.63% inhibition at 5 µg/ml to 26.19% inhibition at 50 µg/ml). These results suggest that PTX3 located at the membrane of late apoptotic macrophages mediates their phagocytosis by phagocytes in a cell model of advanced atherosclerosis.

Effects of atorvastatin on warfarin-induced aortic medial calcification and systolic blood pressure in rats.

The effect of atorvastatin on warfarin-induced aortic medial calcification and systolic blood pressure (SBP) of rats induced by warfarin was studied. Thirty healthy and adult rats were randomly divided into Warfarin group (n=10), Atorvastatin group (n=10) and normal control group (n=10). Caudal arterial pressure of rats was measured once a week, and 4 weeks later, aorta was obtained. Elastic fiber, collagen fiber and calcium accumulation in tunica media of cells were measured by Von Kossa staining. The results showed that warfarin treatment led to elevation of systolic blood pressure and aortic medial calcification. The chronic treatment also increased collagen, but decreased elastin in the aorta. However, the atorvastatin treatment had adverse effects. It was concluded that treatment with atorvastatin presented evidence of blood pressure lowing and calcification reducing. These data demonstrate that atorvastatin protected aortic media from warfarin-induced calcification and elevation of systolic blood pressure.

[Effect of the purariae-isofiavones on estrogen level in normal and ovariectomized rats].

OBJECTIVE: To study the effect of purariae isoflavone on estrogen level in ovariectomized rats. METHOD: 80 rats were divided into four groups randomly, every group with 20 rats: 1. Control group; 2. Normal + purariae isoflavone group; 3. Ovariectomized group; 4. Ovariectomized + purariae isoflavone group. Estrogen level and gonadotropin-releasing hormone level of all rats were measured. RESULT: Thirty days after being ovariectomized, E2, E3 level was significantly lower than that of the first group(P < 0.05). But Testerone, FSH, LH, PRL and GH increased(P < 0.05). After being gastrogavaged with purariae-isolfavone for thirty days, Estrogen level and gonadotropin-relasing hormone level of the second group were significantly lower in various degree than those of normal control group (P < 0.05). But in ovariectomized rats, the estrogen level was recovered (P > 0.05). The gonadotropin-releasing hormone level was increased (P < 0.05). CONCLUSION: Purariae-isoflavone can increase estrogen level to normal in ovariectomized rats by way of increasing the level of gonadotropin-releasing hormone. In normal rats, it has anti-estrogen effect.