Synthesis and Study of Steering of Azido-tetrazole Behavior in Tetrazolo[1,5-c]pyrimidin-5-amine-Based Energetic Materials.

Tetrazoles and their derivatives are essential for compound synthesis due to their versatility, effectiveness, stability in air, and cost-efficiency. This has stimulated interest in developing techniques for their production. In this work, four compounds, tetrazolo[1,5-c]pyrimidin-5-amine (1), N-(4-azidopyrimidin-2-yl)nitramide (2), tetrazolo[1,5-c]pyrimidin-5(6H)-one (3), and tetrazolo[1,5-a]pyrimidin-5-amine (4), were obtained from commercially available reagents and straightforward synthetic methodologies. These new compounds were characterized by infrared (IR), 13C, and 1H NMR spectroscopy, differential scanning calorimetry (DSC), and single-crystal X-ray diffraction. The solvent, temperature, and electron-donating group (EDG) factors that were responsible for the steering of azido-tetrazole equilibrium in all compounds were also studied. In addition, the detonation performance of the target compounds was calculated by using heats of formation (HOFs) and crystal densities. Hirshfeld surface analysis was used to examine the intermolecular interactions of the four synthesized compounds. The results show that the excellent properties of 1-4 are triggered by ionic bonds, hydrogen bonds, and π-π stacking interactions, indicating that these compounds have the potential to be used in the development of high-performance energetic materials. Additionally, DFT analysis is in support of experimental results, which proved the effect of different factors that can influence the azido-tetrazole equilibrium in the synthesized pyrimidine derivatives in the solution.

Determination of 23 related analytes in bone marrow fluid and hippocampus of C57BL/6 mice following cerebral ischemia-reperfusion injury by HPLC-FLD.

The study of brain diseases has long been of interest to researchers worldwide, and stroke is the third leading cause of death that threatens human health. At the same time, cerebral ischemia-reperfusion injury is closely associated with high rates of disability and mortality. The conditions of the 6-aminoquinolyl N-hydroxysccinimidyl carbamate method for the derivatization of amino acids in the bone marrow fluid and hippocampus of C57BL/6 mice with cerebral ischemia-reperfusion injury were explored and optimized, such as the column temperature, concentration of derivatization reagents and mobile phase concentration. The mobile phase consisted of 20 mm sodium acetate solution (phosphoric acid to adjust pH 5.0) and 60% acetonitrile solution at a flow rate of 1 ml min-1 . The 23 analytes were separated and determined in a gradient elution procedure; the correlation coefficient r was >0.9990 in the range 0.1-8.0 µg ml-1 . The results showed that the content of relevant analytes was significantly changed in the cerebral ischemia-reperfusion injury model, and the method was suitable for the simultaneous determination of 23 amino acids in the bone marrow fluid and hippocampus of C57BL/6 mice.

o-Carborane-Based and Atomically Precise Metal Clusters as Hypergolic Materials.

Atomically precise o-carboranealkynyl-protected clusters [Ag14(C4B10H11)12(CH3CN)2]·2NO3 (CBA-Ag) and [Cu6Ag8(C4B10H11)12Cl]NO3 (CBA-CuAg) have been found to exhibit hypergolic activity, such that they are capable of spontaneous ignition and combustion upon contact with the white fuming nitric acid oxidizer. In particular, CBA-CuAg has a short ignition delay time of 15 ms, whereas the o-carboranealkynyl ligand is hypergolically inert. Systematic investigation revealed that the metal cluster core catalyzed the hypergolic behavior of inert o-carboranealkynyl ligand, and Cu doping further accelerated combustion catalysis. This work provides a new prospective in the rational design of novel metal cluster-based hypergolic fuels for propellant application.

Design of New Bridge-Ring Energetic Compounds Obtained by Diels-Alder Reactions of Tetranitroethylene Dienophile.

The density functional theory method was employed to calculate three-dimensional structures for a series of novel explosophores. The design of new molecules (DA1-DA12) was based on the bridge-ring structures that could be formed via Diels-Alder (DA) reaction of selected nitrogen-rich dienes and tetranitroethylene dienophile. The feasibility of the proposed DA reactions was predicted on the basis of the molecular orbital theory. The strong interactions between the HOMO of dienes, with electron-donating groups (Diene2, Diene6, and Diene8), and the LUMO of tetranitroethylene dienophile suggested thermodynamically favorable formation of the desired DA reaction products. In addition to molecular structures of the explored DA compounds, their physicochemical and energetic properties were also calculated in detail. Due to compact bridge-ring structures, new energetic molecules have highly positive heats of formation (up to 1124.90 kJ·mol-1) and high densities (up to 2.04 g·cm-3). Also, as a result of all-right ratios of nitrogen and oxygen, most of the new compounds possess high detonation velocities (8.28-10.02 km·s-1) and high detonation pressures (30.87-47.83 GPa). Energetic compounds DA1, DA4, and DA12 exhibit a superior detonation performance over widely used HMX explosive, and DA5, DA7, and DA10 could be comparable to the state-of-the-art CL-20 and ONC explosives. Our proposed designs and synthetic methodology should provide a platform for the development of novel energetic materials with superior performance.

Simultaneous determination of nine analytes related to the pathogenesis of diabetic encephalopathy in diabetic rat cortex and hippocampus by HPLC-FLD.

The determination of amino acids and monoamine with actions like neurotransmitters or modulators has become increasingly important for studying the relationship between the dysfunction of neurotransmitters and the pathogenesis of diabetic encephalopathy. Here, a high-performance liquid chromatography with fluorescence detection method was developed to simultaneously determine nine monoamines and amino acids including three excitatory neurotransmitters (aspartate, glutamate, and serotonin), four inhibitory neurotransmitters (glycine, γ-aminobutyric acid, taurine, dopamine), a precursor of 5-HT (tryptophan) and methionine using homoserine as the internal standard. The separation was performed on a BDS column with methanol-buffer solution of 35 mmol/L sodium acetate and 5 mmol/L citric acid (pH 6.0) using a simple gradient elution. Several parameters including specificity, precision, and recovery were validated after optimization of the analytical conditions. The developed method was successfully applied to determine the cortex and the hippocampus samples from Sprague-Dawley rats. Our results showed that various neurotransmitters involved in diabetes mellitus may tend to be differentially modulated and present a different alteration tendency at different time course, which might be associated with the duration of diabetes mellitus.

Pharmacokinetics of single- and multiple-dose emtricitabine in healthy male Chinese volunteers.

Emtricitabine (FTC) is used for the treatment of HIV infection and pre-exposure chemoprophylaxis. It is often used in combination with tenofovir disoproxil fumarate (TDF). This study was designed to evaluate FTC pharmacokinetics in healthy male Chinese volunteers. Sixty subjects were recruited into this single-centre, randomised, open-label study and randomly received single (groups A, B and C) or multiple oral doses (once daily for 6 days; groups D, E and F) of 200-mg FTC capsules alone (A and D), or combined with 300-mg TDF tablets (B and E), or 200 mg of FTC plus 300 mg of TDF with a high-fat diet (C and F), respectively. FTC was well-tolerated in all groups. After a single dose, there were no differences in the mean AUC0-∞ values; however, there were significant differences in the mean Tmax values (1.05, 1.40 and 2.10 h for groups A, B and C, respectively; p < 0.05). In the multiple-dose study, our results were significantly different from published t1/2 values following single-dose FTC.

[Anti-tumor effects of a novel cyclophosphamide derivate 9b in vivo and in vitro].

This study is to investigate the anti-tumor activities of a novel cyclophosphamide derivate 4, 6-diphenyl cyclophosphamide (9b) in vivo and in vitro, and its possible mechanism of action. The inhibitory effects of 9b on human hepatoma cell line HepG2, human breast carcinoma cell line MCF-7 and human myeloid leukemia cell line K562 were measured by MTT assay in vitro. Cell cycle distribution and apoptotic rate were evaluated by flow cytometry. To evaluate the anti-tumor effect of 9b in vivo, mouse model bearing inoculated H22 tumor was established. The results indicated that 9b could inhibit the proliferation of HepG2, MCF-7 and K562 cells in a dose and time dependent manner. The ICo50 values of 9b were 32.34 micromol.L-1 to HepG2 cells, 87.07 micromol.L-1 to MCF-7 cells and 149.10 micromol.L-1 to K562 cells after incubation for 48 h. The results of flow cytometry indicated that after being treated for 48 h with different concentrations of 9b, the ratios of HepG2, MCF-7 cells at the Go/G1 phase and K562 cells at the G0/Gl phase and G2/M phase increased significantly compared with control group, and the apoptotic rate increased with the increase of the concentration of 9b. 9b could significantly reduce tumor weight of H22 solid tumor mouse model in vivo. To summarize, 9b showed significantly anti-tumor activity in vivo and in vitro, of which the mechanism might be associated with the change of cell cycle distribution and induction of tumor cell apoptosis.

Lack of association between lipoprotein(a) genetic variants and subsequent cardiovascular events in Chinese Han patients with coronary artery disease after percutaneous coronary intervention.

BACKGROUND: Elevated lipoprotein(a) [Lp(a)] levels predict cardiovascular events incidence in patients with coronary artery disease (CAD). Genetic variants in the rs3798220, rs10455872 and rs6415084 single-nucleotide polymorphisms (SNPs) in the Lp(a) gene (LPA) correlate with elevated Lp(a) levels, but whether these SNPs have prognostic value for CAD patients is unknown. The present study evaluated the association of LPA SNPs with incidence of subsequent cardiovascular events in CAD patients after percutaneous coronary intervention (PCI). METHODS: TaqMan SNP genotyping assays were performed to detect the rs6415084, rs3798220 and rs10455872 genotypes in 517 Chinese Han patients with CAD after PCI. We later assessed whether there was an association of these SNPs with incidence of major adverse cardiovascular events (MACE: cardiac death, nonfatal myocardial infarction, ischemic stroke and coronary revascularization). Serum lipid profiles were also determined using biochemical methods. RESULTS: Only the rs6415084 variant allele was associated with higher Lp(a) levels [41.3 (20.8, 74.6) vs. 18.6 (10.3, 40.9) mg/dl, p < 0.001]. During a 2-year follow-up period, 102 patients suffered MACE, and Cox regression analysis demonstrated that elevated Lp(a) (≥30 mg/dl) levels correlated with increased MACE (adjusted HR, 1.69; 95% CI 1.13-2.53), but there was no association between LPA genetic variants (rs6415084 and rs3798220) and MACE incidence (p > 0.05). CONCLUSIONS: Our data did not support a relationship between genetic LPA variants (rs6415084 and rs3798220) and subsequent cardiovascular events after PCI in Chinese Han CAD patients.

Splicing oxygen-rich multidentate ligands and characteristic metals to construct flame colorants: abundant structures and attractive colors.

Tetranitroethane (TNE), an energetic compound with high-nitrogen (N%, 26.7%) and oxygen (O%, 60.9%) content, is deprotonated by alkali and alkaline earth metal bases to form the corresponding metal salts of TNE which are characterized by FT-IR spectroscopy, elemental analysis, and single crystal X-ray diffraction. All the prepared energetic metal salts show excellent thermal stabilities, and the decomposition temperatures of EP-3, EP-4, and EP-5 are higher than 250 °C, due to the numerous coordination bonds of the complexes. Furthermore, the energy of formation of the nitrogen-rich salts were calculated utilizing heat of combustion. The detonation performances were calculated with the EXPLO5 software, and the impact and friction sensitivities were determined. EP-7 shows excellent energy performance (P = 30.0 GPa, VD = 8436 m s-1). EP-3, EP-4, EP-5, and EP-8 are more sensitive to mechanical stimulation. These alkali and alkaline earth metal salts of TNE show good monochromaticity by atomic emission spectroscopy (visible light), and may be used as potential flame colorants in pyrotechnics.

Development and validation of a simple model to predict functionally significant coronary artery disease in Chinese populations: A two-center retrospective study.

Objectives: This study sought to derive and validate a simple model combining traditional clinical risk factors with biomarkers and imaging indicators easily obtained from routine preoperative examinations to predict functionally significant coronary artery disease (CAD) in Chinese populations. Methods: We developed five models from a derivation cohort of 320 patients retrospective collected. In the derivation cohort, we assessed each model discrimination using the area under the receiver operating characteristic curve (AUC), reclassification using the integrated discrimination improvement (IDI) and net reclassification improvement (NRI), calibration using the Hosmer-Lemeshow test, and clinical benefit using decision curve analysis (DCA) to derive the optimal model. The optimal model was internally validated by bootstrapping, and external validation was performed in another cohort including 96 patients. Results: The optimal model including 5 predictors (age, sex, hyperlipidemia, hs-cTnI and LVEF) achieved an AUC of 0.807 with positive NRI and IDI in the derivation cohort. Moreover, the Hosmer-Lemeshow test showed a good fit, and the DCA demonstrated good clinical net benefit. The C-statistic calculated by bootstrapping internal validation was 0.798, and the calibration curve showed adequate calibration (Brier score = 0.179). In the external validation cohort, the optimal model performance was acceptable (AUC = 0.704; Brier score = 0.20). Finally, a nomogram based on this model was constructed to facilitate its use in clinical practice. Conclusions: A simple model combined clinical risk factors with hs-cTnI and LVEF improving the prediction of functionally significant CAD in Chinese populations. This attractive model may be a choice for clinicians to risk stratification for CAD.

Contrast medium volume to creatinine clearance ratio: a predictor of contrast-induced nephropathy in the first 72 hours following percutaneous coronary intervention.

OBJECTIVES: To investigate the predictive value of the contrast media volume to creatinine clearance (V/CrCl) ratio for the risk of contrast-induced nephropathy (CIN) (i.e., within 48-72 hr) and to determine a relatively safe V/CrCl cut-off value to avoid CIN in patients following percutaneous coronary intervention (PCI). BACKGROUND: The V/CrCl ratio is a pharmacokinetic risk factor for an early abnormal increase in serum creatinine (i.e., within 24 hr) after PCI. METHODS: V/CrCl ratios were obtained from 1,140 consecutive consenting patients after unselective PCI. Receiver-operator characteristic (ROC) curves were used to identify the optimal sensitivity for the observed range of V/CrCl. The predictive value of V/CrCl for the risk of CIN was assessed using multivariate logistic regression. RESULTS: Fifty-five (4.8%) patients out of 1,140 developed CIN. There was a significant association between higher V/CrCl ratio values and risk of CIN in the overall population: 1.4%, 1.4%, 5.7%, and 10.9% for quartile 1 (Q1) of the V/CrCl value (<1.56, n = 283), Q2 (1.56-2.27, n = 289), Q3 (2.28-3.42, n = 282), and Q4 (>3.42, n = 285) of contrast, respectively (P < 0.001). ROC curve analysis indicated that a V/CrCl ratio of 2.62 was a fair discriminator for CIN (C-statistic 0.73). After adjusting for other known predictors of CIN, V/CrCl ratios > 2.62 remained significantly associated with CIN (odds ratio: 2.20; 95% confidence interval: 1.00-4.81, P < 0.05). CONCLUSION: A V/CrCl ratio > 2.62 was a significant and independent predictor of CIN after PCI in unselected patients.

A Risk Stratification Scheme for In-Hospital Cardiogenic Shock in Patients With Acute Myocardial Infarction.

Objective: Cardiogenic shock (CS) is the leading cause of death in patients with acute myocardial infarction (AMI) despite advances in care. This study aims to derive and validate a risk score for in-hospital development of CS in patients with AMI. Methods: In this study, we used the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) registry of 76,807 patients for model development and internal validation. These patients came from 158 tertiary hospitals and 82 secondary hospitals between 2014 and 2019, presenting AMI without CS upon admission. The eligible patients with AMI were randomly assigned to derivation (n = 53,790) and internal validation (n = 23,017) cohorts. Another cohort of 2,205 patients with AMI between 2014 and 2016 was used for external validation. Based on the identified predictors for in-hospital CS, a new point-based CS risk scheme, referred to as the CCC-ACS CS score, was developed and validated. Results: A total of 866 (1.1%) and 39 (1.8%) patients subsequently developed in-hospital CS in the CCC-ACS project and external validation cohort, respectively. The CCC-ACS CS score consists of seven variables, including age, acute heart failure upon admission, systolic blood pressure upon admission, heart rate, initial serum creatine kinase-MB level, estimated glomerular filtration rate, and mechanical complications. The area under the curve for in-hospital development of CS was 0.73, 0.71, and 0.85 in the derivation, internal validation and external validation cohorts, respectively. Conclusion: This newly developed CCC-ACS CS score can quantify the risk of in-hospital CS for patients with AMI, which may help in clinical decision making. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02306616.

[Influences of different aspiration results by aspiration thrombectomy catheter in emergent percutaneous coronary intervention for patents with acute myocardial infarction].

OBJECTIVE: To evaluate the influences of different aspiration results by Diver C.E. aspiration thrombectomy catheter on myocardium perfusion and clinical outcomes during emergency PCI (percutaneous coronary intervention) for the patients with acute ST segment elevation myocardial infarction (STEMI). METHODS: The patients undergoing emergent PCI and using Diver C.E. aspiration thrombectomy catheter with STEMI from July 2008 to February 2011 were enrolled into the study group. According to the aspiration results, they were divided into 2 groups: aspiration-positive group (n = 38) and aspiration-negative group (n = 28). And those undergoing routine PCI alone during the same period were enrolled into the control group (n = 66). The baseline profiles, immediate post-operative CAG (coronary angiography) and follow-up data were compared. RESULTS: No significant baseline differences existed among 3 groups. Compared with the control group, all parameters significantly improved in the aspiration-positive group. But in the aspiration-negative group, the differences of slow flow/no-reflow and major adverse cardiovascular events (MACE) were insignificant (P > 0.05). Compared with the aspiration-negative group, cTFC (29 ± 9 vs 35 ± 11 frames, P < 0.05), ST segment (90% ± 20% vs 76% ± 25%, P < 0.05) and the peak serum levels of CK-MB (creatine kinase-MB) and TnT (troponin-T) [CK-MB: (201 ± 86) U/L vs (264 ± 93) U/L, P < 0.05; TnT: (41 ± 21) µg/L vs (60 ± 24) µg/L, P < 0.05] decreased significantly. But the differences in slow flow/no-reflow and MACE were insignificant (P > 0.05). CONCLUSION: Application of Diver CE. during emergent PCI i.s both safe and efficacious for STEMI patients with heavier thrombus burden. It may improve distal myocardium perfusion and abate myocardial damage. The patients with positive aspiration results have better clinical outcome. But the efficacy of aspiration-negative patients needs further evaluations.

The relationship between pre-procedural elevated arterial lactate and contrast-induced nephropathy following primary percutaneous coronary intervention.

BACKGROUND: Risk stratification has been one of the main steps in preventing contrast-induced nephropathy (CIN), which is a common complication after percutaneous coronary intervention (PCI). Elevated arterial lactate is a biomarker indicating severe disease condition and post-intervention complications. The relationship between lactate and CIN has not been established. This study is performed to investigate the relationship between elevated arterial lactate level and contrast-induced nephropathy (CIN). METHODS: Patients diagnosed with ST-segment elevated myocardial infarction (STEMI) were prospectively enrolled, with lactate measured within 0.5-1 hours before primary percutaneous coronary intervention (PCI). Patients with cardiopulmonary resuscitation, any forms of severe anaerobic condition, or end-stage renal disease undergoing dialysis were excluded. CIN was defined as an increase in serum creatinine ≥0.5 mg/dL or 25% within 72 hours after PCI. The Mehran Risk Score (MRS) is widely regarded as a classic risk model for CIN and the risk factors of MRS were applied in our multivariate regression analysis. RESULTS: Of the 227 enrolled patients, 47 (20.7%) developed CIN according to the definition. The mean lactate level was higher in the CIN group than in the non-CIN group (2.68±2.27 vs. 1.74±1.94, P<0.001). The arterial lactate level ≥2.0 mmol/L had 57.5% sensitivity and 75.6% specificity in predicting CIN. The performance of the lactate level in discriminating CIN was similar to that of the MRS (AUClac =0.707 vs. AUCMRS =0.697, P=0.86). After adjusting for other risk factors, lactate ≥2.0 mmol/L still significantly predicted CIN (odds ratio =3.77, 95% CI, 1.77-7.99, P=0.001). CONCLUSIONS: An arterial lactate level of ≥2.0 mmol/L is associated with CIN in STEMI patients after primary PCI.

Shock Index-C: An Updated and Simple Risk-Stratifying Tool in ST-Segment Elevation Myocardial Infarction.

Background: Shock index (heart rate/systolic blood pressure, SI) is a simple scale with prognostic value in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). The present study introduces an updated version of SI that includes renal function. Methods: A total of 1,851 consecutive patients with STEMI undergoing PCI were retrospectively included at Cardiac Care Unit in Guangdong Provincial People's Hospital and divided into two groups according to their admission time: derivation database (from January 2010 to December 2013, n = 1,145) and validation database (from January 2014 to April 2016, n = 706). Shock Index-C (SIC) was calculated as (SI × 100)-estimated CCr. Calibration was evaluated using the Hosmer-Lemeshow statistic. The predictive power of SIC was evaluated using receiver operating characteristic (ROC) curve analysis. Results: The predictive value and calibration of SIC for in-hospital death was excellent in derivation [area under the curve (AUC) = 0.877, p < 0.001; Hosmer-Lemeshow chi-square = 3.95, p = 0.861] and validation cohort (AUC = 0.868, p < 0.001; Hosmer-Lemeshow chi-square = 5.01, p = 0.756). SIC exhibited better predictive power for in-hospital events than SI (AUC: 0.874 vs. 0.759 for death; 0.837 vs. 0.651 for major adverse clinical events [MACEs]; 0.707 vs. 0.577 for contrast-induced acute kidney injury [CI-AKI]; and 0.732 vs. 0.590 for bleeding, all p < 0.001). Cumulative 1-year mortality was significantly higher in the upper SIC tertile (log-rank = 131.89, p < 0.001). Conclusion: SIC was an effective predictor of poor prognosis and may have potential as a novel and simple risk stratification tool for patients with STEMI undergoing PCI.

A risk score to predict in-hospital mortality in patients with acute coronary syndrome at early medical contact: results from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) Project.

BACKGROUND: A number of models have been built to evaluate risk in patients with acute coronary syndrome (ACS). However, accurate prediction of mortality at early medical contact is difficult. This study sought to develop and validate a risk score to predict in-hospital mortality among patients with ACS using variables available at early medical contact. METHODS: A total of 62,546 unselected ACS patients from 150 tertiary hospitals who were admitted between 2014 and 2017 and enrolled in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project, were randomly assigned (at a ratio of 7:3) to a training dataset (n=43,774) and a validation dataset (n=18,772). Based on the identified predictors which were available prior to any blood test, a new point-based risk score for in-hospital death, CCC-ACS score, was derived and validated. The CCC-ACS score was then compared with Global Registry of Acute Coronary Events (GRACE) risk score. RESULTS: The in-hospital mortality rate was 1.9% in both the training and validation datasets. The CCC-ACS score, a new point-based risk score, was developed to predict in-hospital mortality using 7 variables that were available before any blood test including age, systolic blood pressure, cardiac arrest, insulin-treated diabetes mellitus, history of heart failure, severe clinical conditions (acute heart failure or cardiogenic shock), and electrocardiographic ST-segment deviation. This new risk score had an area under the curve (AUC) of 0.84 (P=0.10 for Hosmer-Lemeshow goodness-of-fit test) in the training dataset and 0.85 (P=0.13 for Hosmer-Lemeshow goodness-of-fit test) in the validation dataset. The CCC-ACS score was comparable to the Global Registry of Acute Coronary Events (GRACE) score in the prediction of in-hospital death in the validation dataset. CONCLUSIONS: The newly developed CCC-ACS score, which utilizes factors that are acquirable at early medical contact, may be able to stratify the risk of in-hospital death in patients with ACS. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02306616.

Evaluation on monoamine neurotransmitters changes in depression rats given with sertraline, meloxicam or/and caffeic acid.

Inflammation drives the development of depression and may affect neurotransmitters and thus neurocircuits increase the risk of depression. To investigate the influence of inhibition of inflammatory pathways on the biogenic amine neurotransmitters metabolism in depressive rats, sertraline, and meloxicam, the inhibitors of arachidonic acid - cyclooxygenase-2/lipoxygenase (AA-COX-2/5-LO) pathways, were given to depressive rats. After the development of depression model by chronic unpredictable mild stress (CUMS) for 6 weeks, Successful modeling rats were selected and randomly divided into CUMS group and medication administration group. After given medicine, The biogenic amine neurotransmitters in rat cortex and hippocampus were measured by high-performance liquid chromatography equipped with an electrochemical detector (HPLC-ECD). Compared with the normal group, the concentration of norepinephrine (NE) significantly decreased and the concentrations of Tyrosine (Tyr), Tryptophan (Trp), 3,4-dihydroxyphenyl acetic acid (DOPAC), 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) significantly increased in the CUMS group. Sertraline significantly inhibited the elevation of 5-HIAA. Meloxicam inhibited the decrease of NE level in CUMS-induced rat and the increase of Trp, MHPG, and 5-HIAA level in a dose-dependent manner. Caffeic acid inhibited the decrease of NE and the increase of Trp and MHPG in a dose-dependent manner. The inhibition of AA-COX-2/5-LO pathways can improve the behaviors of depression rats and suppress CUMS-induced changes in biogenic amines. Compared with the single-dose lipoxygenase (5-LO) or Cyclooxygenase-2 (COX-2) inhibitor, the combination treatment with meloxicam 1 mg/kg and caffeic acid 10 mg/kg have no significant improvement in CUMS-induced depression behavior and the level of cortical monoamine neurotransmitters and their metabolites.

Phosphate-solubilizing bacteria will not significantly remobilize soil cadmium remediated by weathered coal.

Cadmium (Cd) re-mobilize by phosphate-solubilizing bacteria (PSB) from immobilization contaminated soil has drawn great attention due to its serious threat to human health through food chain. However, Cd binding with weathered coal (WC), an effective Cd immobilization material, will be re-mobilized by PSB or not is still unclear. In this study, the soil and sand pots with Cd were respectively mixed with the weight fractions of 0‰, 2‰, and 3‰ WC, inoculated with or without PSB, and planted with Amaranthus mangostanus L. The experimental results indicated that: (i) Cd in soil was transformed into organic fraction with WC, which has been led to the Cd accumulation concentrations in roots and shoots reduced by 38.8% and 20.5%, respectively; (ii) PSB could promote the concentration of exchangeable-Cd fraction and soil Cd uptake by amaranth in all treatments; and (iii) WC application in sand pot respectively reduced the Cd accumulation by 47.5% in roots and 24.1% in shoots, but PSB inoculation showed no significant effect on Cd accumulation in plants under WC application. SEM, zeta potential, and FT-IR results showed that PSB inoculation after Cd immobilized by WC had no influence on the microstructure, amount of negative charge, type, and content of functional groups in WC, indicating that organic fraction Cd in WC was not re-mobilized by PSB. Therefore, the application of WC in contaminated soil was conducive to transforming Cd in organic-bound forms and intensifying Cd immobilization effects.

Protective effects and mechanism of total coptis alkaloids on a beta 25-35 induced learning and memory dysfunction in rats.

OBJECTIVE: To observe the effect of total coptis alkaloids (TCA) on beta -amyloid peptide (A beta 25-35) induced learning and memory dysfunction in rats, and to explore its mechanism. METHODS: Forty male Wistar rats were randomly divided into four groups: the control group, the model group, the TCA low dose (60 mg/kg) group and the TCA high dose (120 mg/kg) group, 10 in each. A beta 25-35 (5microl, 2 microg/microl) was injected into bilateral hippocampi of each rat to induce learning and memory dysfunction. TCA were administered through intragavage for consecutive 15 days. Morris Water Maze test was used to assess the impairment of learning and memory; concentration of malondialdehyde (MDA) in cerebral cortex was determined by thiobarbituric acid reactive substance to indicate the level of lipid peroxidation in brain tissues; activity of manganese-superoxide dismutase (Mn-SOD) in cerebral cortex was determined by xanthine-oxidase to indicate the activity of the enzyme; and NF- kappa B protein expression in cerebral cortex was measured by SP immunohistochemistry. RESULTS: (1) Morris Water Maze test showed that, during the 4 consecutive days of acquisition trials, the rats in the model group took longer latency and searching distance than those in the control group (P<0.01), which could be shortened by high dose TCA (P<0.05); during the spatial probe trial on the fifth day, the rats in the model group took shorter searching time and distance on the previous flat area than those in the control group (P<0.01), which could be prolonged after TCA treatment (for low dose group, P<0.05; for high dose group, P<0.01). (2) Analysis of cerebral cortical tissues showed that, compared with the control group, MDA level got significantly increased and Mn-SOD activity decreased in the model group (both P<0.01). After having been treated with TCA, the MDA level got significantly decreased (P<0.05 and P<0.01 respectively for low and high dose group), while relative increase of Mn-SOD activity only appeared in high dose group (P<0.05). (3) Immunohistochemistry analysis showed the protein expression of NF- kappa B got significantly increased after modeling, while high dose TCA can significantly inhibit it. CONCLUSION: TCA could improve A beta 25-35 induced dysfunction of learning and memory in rats, and its protective mechanism is associated with its actions in decreasing MDA level, increasing Mn-SOD activity and inhibiting the expression of NF-kappa B in cerebral cortex.

Preprocedural High-Sensitivity C-Reactive Protein Predicts Contrast-Induced Nephropathy and Long-Term Outcome After Coronary Angiography.

We investigated whether high-sensitivity C-reactive protein (hsCRP) levels were associated with contrast-induced nephropathy (CIN) and long-term mortality after coronary angiography (CAG). Patients (N = 2133) undergoing CAG with preprocedural hsCRP were consecutively enrolled. High-sensitivity C-reactive protein was measured before angiography. Median follow-up was 2.3 years. The overall incidence of CIN was 2.77% (59 of 2133). There was a positive trend of hsCRP quartiles (Q) with rates of CIN: 0.9% for Q1 (<1.6 mg/L), 0.9% for Q2 (1.6-3.9 mg/L), 2.4% for Q3 (4.0-11.3mg/L), and 6.8% for Q4 (>11.3 mg/L; P < .05). The receiver operating characteristic (ROC) analysis showed that the cutoff point of hsCRP was 7.3 mg/L for predicting CIN with a 72.7% sensitivity and a 67.0% specificity (area under the curve [AUC] = 0.742, 95% confidence interval [CI] 0.672-0.810; P < .05). The predictive value of hsCRP was similar to the Mehran score for CIN (AUChsCRP = 0.742 vs AUCMehran = 0.801; P = .228). After adjustment for other potential risk factors, hsCRP >7.3 mg/L still was an independent predictor of CIN (odds ratio [OR] = 2.83, 95% CI: 1.44-5.58; P = .003). Furthermore, hsCRP >7.3 mg/L was associated with higher mortality (OR = 2.04, 95% CI: 1.30-3.19; P = .002).