A nomogram based on endothelial function and conventional risk factors predicts coronary artery disease in hypertensives.

BACKGROUND: There is currently a lack of a precise, concise, and practical clinical prediction model for predicting coronary artery disease (CAD) in patients with essential hypertension (EH). This study aimed to construct a nomogram to predict CAD in patients with EH based on flow-mediated dilation (FMD) of brachial artery and traditional risk factors. METHODS: Clinical data of 1752 patients with EH were retrospectively collected. High-resolution vascular ultrasound was used to detect FMD in all patients at the Fujian Hypertension Research Institute, China. Patients were divided into two groups, i.e. training group (n = 1204, from August 2000 to December 2013) and validation group (n = 548, from January 2014 to May 2016) according to the time of enrollment. Independent predictors of CAD were analyzed by multivariable logistic regression in the training group, and a nomogram was constructed accordingly. Finally, we evaluated the discrimination, calibration, and clinical applicability of the model using the area under curve (AUC) of receiver operating characteristic analysis, calibration curve combined with Hosmer-Lemeshow test, and decision curve, respectively. RESULTS: There were 263 (21.8%) cases of EH combined with CAD in the training group. Multivariate logistic regression showed that FMD, age, duration of EH, waist circumference, and diabetes mellitus were independent influencing factors for CAD in EH patients. Smoking which was close to statistical significance (P = 0.062) was also included in the regression model to increase the accuracy. Ultimately, the nomogram for predicting CAD in EH patients was constructed according to above predictors after proper transformation. The AUC values of the training group and the validation group were 0.799 (95%CI 0.770-0.829) and 0.836 (95%CI 0.787-0.886), respectively. Calibration curve and Hosmer-Lemeshow test showed that the model had good calibration (training group: χ2 = 0.55, P = 0.759; validation group: χ2 = 1.62, P = 0.446). The decision curve also verified the clinical applicability of the nomogram. CONCLUSION: The nomogram based on FMD and traditional risk factors (age, duration of EH disease, smoking, waist circumference and diabetes mellitus) can predict CAD high-risk group among patients with EH.

Per- and polyfluoroalkyl substances exposure and bone mineral density in the U.S. population from NHANES 2005-2014.

BACKGROUND: Environmental exposures such as perfluoroalkyl substances (PFASs) were considered potential risks for bone mineral density (BMD). OBJECTIVE: To examine the associations between PFASs and BMD among the U.S. population. METHODS: This study included a total of 6416 participants from the National Health and Nutrition Examination Survey (NHANES 2005-2014). Multiple linear regression models were used to analyze the associations between serum PFASs and BMD and the coefficient ß with 95% confidence intervals (95% CI) was calculated as the effect estimate. Covariates such as age, race, BMI, smoking, alcohol intake, milk intake, and physical activity were adjusted in these models. Additionally, gender and menopausal period were considered in further subgroup analyses. RESULTS: Based on the combined data of NHANES 2005-2014, the effects from exposure to PFASs on BMD were found with gender and menopausal status differences. Positive associations were found in PFOA (ß = 0.010; 95% CI: 0.003, 0.016), PFHxS (ß = 0.007; 95% CI: 0.003, 0.012), and PFNA (ß = 0.001; 95% CI: 0.001, 0.017) in total population. Negative associations for PFOA (ß = -0.020; 95% CI: -0.029, -0.012), PFOS (ß = -0.011; 95% CI: -0.028, -0.011), PFHxS (ß = -0.019; 95% CI: -0.025, -0.013), PFDE (ß = -0.010; 95% CI: -0.016, -0.005), and PFNA (ß = -0.011; 95% CI: -0.021, -0.002) were found in women, while no significant association was found in men. In further subgroup analyses, women in pre-menopause status showed consistent negative associations. SIGNIFICANCE: PFASs exposure may be associated with BMD and gender and menopausal status confound the associations.

Intraperitoneal hypertension, a novel risk factor for sepsis-associated encephalopathy in sepsis mice.

Sepsis associated encephalopathy (SAE), appears often indicates the deterioration of the sepsis disease and which have high risk of death. Although several mechanism and hypotheses have been proposed and studied, there is no breakthrough in the treatment of SAE. We performed a systematic research to evaluate the effect of intraperitoneal pressure on SAE. A mice model of sepsis was established by intraperitoneal injection of endotoxin. A total of 48 female BALB/c mouse (30 days old) were randomly divided into a control group (n = 12) and an injection of endotoxin referred to bacterial lipopolysaccharide (LPS) group (n = 12). Intraperitoneal hypertension (IAH) referred to IAH group (n = 12), and LPS + IAH group (n = 12). Following sepsis induction, diagnosis, the brains were analyzed for both function and ultrastructural morphology.We determined that IAH exacerbated sepsis induces sepsis-associated encephalopathy when examining low score of neurological function and more delta wave in EEG, increased neuronal edema in LPS + IAH group, as well as an escalation of Bax and Cleaved-caspase-3, Cleaved-parp, and reduction of Bcl-2 and Mfsd2a in LPS + IAH group. Therefore, IAH can exacerbate and increase incident rate of sepsis-related encephalopathy in sepsis mice by promoting neuronal apoptosis and destruction of the blood-brain barrier.

Hydrogen sulfide improves neural function in rats following cardiopulmonary resuscitation.

The alleviation of brain injury is a key issue following cardiopulmonary resuscitation (CPR). Hydrogen sulfide (H2S) is hypothesized to be involved in the pathophysiological process of ischemia-reperfusion injury, and exerts a protective effect on neurons. The aim of the present study was to investigate the effects of H2S on neural functions following cardiac arrest (CA) in rats. A total of 60 rats were allocated at random into three groups. CA was induced to establish the model and CPR was performed after 6 min. Subsequently, sodium hydrosulfide (NaHS), hydroxylamine or saline was administered to the rats. Serum levels of H2S, neuron-specific enolase (NSE) and S100ß were determined following CPR. In addition, neurological deficit scoring (NDS), the beam walking test (BWT), prehensile traction test and Morris water maze experiment were conducted. Neuronal apoptosis rates were detected in the hippocampal region following sacrifice. After CPR, as the H2S levels increased or decreased, the serum NSE and S100ß concentrations decreased or increased, respectively (P<0.0w. The NDS results of the NaHS group were improved compared with those of the hydroxylamine group at 24 h after CPR (P<0.05). In the Morris water maze experiment, BWT and prehensile traction test the animals in the NaHS group performed best and rats in the hydroxylamine group performed worst. At day 7, the apoptotic index and the expression of caspase-3 were reduced in the hippocampal CA1 region, while the expression of Bcl-2 increased in the NaHS group; and results of the hydroxylamine group were in contrast. Therefore, the results of the present study indicate that H2S is able to improve neural function in rats following CPR.

Model of cardiac arrest in rats by transcutaneous electrical epicardium stimulation.

OBJECTIVE: To establish a new model of cardiac arrest (CA) in rats by transcutaneous electrical epicardium stimulation. METHODS: Two acupuncture needles connected to the anode and cathode of a stimulator were transcutaneously inserted into the epicardium as electrodes. The stimulating current was steered to the epicardium and the stimulation was maintained for 3 min to induce CA. Cardiopulmonary resuscitation (CPR) was performed at 6 min after a period of nonintervention. RESULTS: CA was successfully induced in a total of 20 rats. The success rate of induction was 12/20 at the current intensity of 1 mA; and reached 20/20 when the current intensity was increased to 2 mA. After the electrical stimulation, the femoral blood pressure quickly dropped below 25 mmHg and the arterial pulse waveform disappeared. The average time from the electrical stimulation to CA induction was 5.10 (+/-2.81) s. When the electrical stimulation stopped, 18/20 rats had ventricular fibrillation and 2/20 rats had pulseless electrical activity. CPR was performed for averagely 207.4 (+/-148.8) s. The restoration of spontaneous circulation (ROSC) was 20/20. The death rate within 4h after ROSC was 5/20, and the 72-h survival rate was 10/20. There were only two cases of complications, a minor muscle contraction and a minor lung lobe injury. CONCLUSION: The model of CA in rats induced by transcutaneous electrical epicardium stimulation is a stable model that requires low-intensity current and has fewer complications. This model may provide another option for experimental research of CA induced by malignant arrhythmia (especially VF).

[Change of hydrogen sulfide content in serum of rats after cardiopulmonary resuscitation].

AIM: To investigate variation of hydrogen sulfide (H2S) in serum of rats after cardiopulmonary resuscitation (CPR) and explore its pathophysiological role in CPR. METHODS: The 30 male SD rats were randomly divided into control group (n=6) and experimental group (n=24), then models of cardiac arrest (CA) were established in rats of experimental group by transcutaneous electrical epicardium stimulation. Blood samples were collected before CA, at 2, 4, 6, 8, 10 and 12 h after restoration of spontaneous circulation (ROSC) for testing the serum levels of H2S, at the same time rectal temperature (Tr), mean arterial pressure (MAP), heart rate (HR) and respiration rate (R) were recorded. Next to analyze the dynamic variation of H2S content in serum of the rats after CPR and its correlation of the above-mentioned signs of life. RESULTS: (1) In experimental group, all of the 24 rats were successfully induced CA and resuscitation; at end points (12 h after ROSC) there were 14 rats alive and their vital signs were stable. There was no death in the control group. (2) The variation trend of H2S content in serum was different between experimental group and the control (F=12.226, P=0.003). In experimental group, H2S content in serum increased dramatically after CPR and reached peak at 6 h after ROSC, then return to the similar level of the control group. (3) H2S content in serum was negatively correlated with Tr (partial r=-0.556, P=0.000) and MAP (partial r=-0.240, P=0.002). But it wasn't correlated with HR and R (P>0.05). CONCLUSION: Change of H2S content in serum of rats after CPR may be a manifestation of compensatory response after ROSC and participate in physiological processes such as body temperature and blood pressure regulation. But as for its precisely mechanisms, it still needs to be studied further.

Pluripotency-associated genes in human nasopharyngeal carcinoma CNE-2 cells are reactivated by a unique epigenetic sub-microenvironment.

BACKGROUND: There is increasing evidence that cancers contain their own stem-like cells, and particular attention has been paid to one subset of cancer-stem cells termed side population (SP). Stem cells under normal physical conditions are tightly controlled by their microenvironment, however, the regulatory role of the microenvironment surrounding cancer stem cells is not well characterized yet. In this study we found that the phenotype of SP can be "generated" by macrophage-like cells under conditioned culture. Furthermore the gene regulation pathway involved in cellular reprogramming process was investigated. METHODS: The selection and identification of SP in 50 CNE-2 single cell clones were performed by flow cytometry. The transwell assay and immunofluorescence staining were used to measure migration and cancer stem cell characters of non-SP single clone cells cultured with conditioned medium respectively. The subtraction suppression hybridization (SSH) technique and northern blotting analysis was applied to explore the pluripotency-associated genes under a unique epigenetic sub-microenvironment. RESULTS: Among 50 clones, only one did not possess SP subpopulation while others did. The non-SP cells induced by macrophage-like cells showed more aggressive characters, which increased cell migration compared with the control cells and showed some fraction of SP phenotype. These cells expressed distinguished level of pluripotency-associated genes such as ADP-ribosylation factor-like 6 interacting protein (ARMER), poly (rC) binding protein 1 (PCBP1) and pyruvate dehydrogenase E1-beta subunit (PDHB) when subjected to the environment. CONCLUSION: To our knowledge, this is the first study to demonstrate that non-SP single-clone cells can be induced to generate a SP phenotype when they are cultured with conditioned medium of macrophage-like cells, which is associated with the reactivation of pluripotency-associated genes.

[Reactive oxygen species scavenger protects cardiac cells against injuries induced by chemical hypoxia].

OBJECTIVE: To investigate the protective effect of reactive oxygen species (ROS) scavenger, N-acetyl-L-cysteine (NAC), against H9c2 cardiomyocytes from injuries induced by chemical hypoxia. METHODS: H9c2 cells were treated with cobalt chloride (CoCl2), a chemical hypoxia-mimetic agent, to establish the chemical hypoxia-induced cardiomyocyte injury model. NAC was added into the cell medium 60 min prior to CoCl2 exposure. The cell viability was evaluated using cell counter kit (CCK-8), and the intercellular ROS level was measured by 2', 7'- dichlorfluorescein-diacetate (DCFH-DA) staining and photofluorography. Mitochondrial membrane potential (MMP) of the cells was observed by Rhodamine123 (Rh123) staining and photofluorography, and the ratio of GSSG/ (GSSG+GSH) was calculated according to detection results of the GSSG kit. RESULTS: Exposure of H9c2 cardiomyocytes to 600 micromol/L CoCl2 for 36 h resulted in significantly reduced cell viability. Pretreatment with NAC at the concentrations ranging from 500 to 2000 micromol/L 60 min before CoCl2 exposure dose-dependently inhibited CoCl2-induced H9c2 cell injuries, and obviously increased the cell viability. NAC at 2000 micromol/L obviously inhibited the oxidative stress induced by CoCl2, decreased the ratio of GSSG/(GSSG+GSH), increased ROS level, and antagonized CoCl2-induced inhibition on MMP. CONCLUSION: NAC offers obvious protective effect on H9c2 cardiomyocytes against injuries induced by chemical hypoxia by decreasing in the ratio of GSSG/(GSSG+GSH) and ROS level and ameliorating MMP.