BACKGROUND: The Global Registry of Acute Coronary Events (GRACE) score is recommended by current ST-elevation myocardial infarction (STEMI) guidelines. But it has inherent defects. The present study aimed to investigate the more compatible risk stratification for Chinese patients with STEMI and to determine whether the addition of biomarkers to the Korea Acute Myocardial Infarction Registry (KAMIR) score could enhance its predictive value for long-term outcomes. METHODS: A total of 1093 consecutive STEMI patients were included and followed up 48.2 months. Homocysteine, hypersensitive C-reactive protein (hs-CRP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were detected. The KAMIR score and the GRACE score were calculated. The performance between the KAMIR and the GRACE was compared. The predictive power of the KAMIR alone and combined with biomarkers were assessed by the receiver-operating characteristic (ROC) curve. RESULTS: The KAMIR demonstrated a better risk stratification and predictive ability than the GRACE (death: AUC = 0.802 vs. 0.721, P < 0.001; major adverse cardiovascular events (MACE): AUC = 0.683 vs. 0.656, P < 0.001). It showed that the biomarkers could independently predict death [homocysteine: HR = 1.019 (1.015-1.024), P < 0.001; hs-CRP: HR = 1.052 (1.000-1.104), P = 0.018; NT-pro BNP: HR = 1.142 (1.004-1.280), P = 0.021] and MACE [homocysteine: HR = 1.019 (1.015-1.024), P < 0.001; hs-CRP: HR = 1.012 (1.003-1.021), P = 0.020; NT-pro BNP: HR = 1.136 (1.104-1.168), P = 0.006]. When they were used in combination with the KAMIR, the area under the ROC curve (AUC) significantly increased for death [homocysteine: AUC = 0.802 vs. 0.890, Z = 5.982, P < 0.001; hs-CRP: AUC = 0.802 vs. 0.873, Z = 3.721, P < 0.001; NT-pro BNP: AUC = 0.802 vs. 0.871, Z = 2.187, P = 0.047; homocysteine, hs-CRP and NT-pro BNP: AUC = 0.802 vs. 0.940, Z = 6.177, P < 0.001] and MACE [homocysteine: AUC = 0.683 vs. 0.771, Z = 6.818, P < 0.001; hs-CRP: AUC = 0.683 vs. 0.712, Z = 2.022, P = 0.031; NT-pro BNP: AUC = 0.683 vs. 0.720, Z = 2.974, P = 0.003; homocysteine, hs-CRP and NT-pro BNP: AUC = 0.683 vs. 0.789, Z = 6.900, P < 0.001]. CONCLUSION The KAMIR is better than the GRACE in risk stratification and prognosis prediction in Chinese STEMI patients. A combination of above-mentioned biomarkers can develop a more predominant prediction for long-term outcomes.
Biomarkers ; blood ; C-Reactive Protein ; metabolism ; Humans ; Myocardial Infarction ; blood ; metabolism ; Natriuretic Peptide, Brain ; blood ; metabolism ; Peptide Fragments ; blood ; metabolism ; ROC Curve ; Registries ; Risk Factors ; ST Elevation Myocardial Infarction ; blood ; metabolism

Animals ; Esophagus ; metabolism ; Glucagon-Like Peptide 2 ; pharmacology ; Intestinal Mucosa ; drug effects ; metabolism ; Intestine, Small ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Stomach ; metabolism

AIMTo investigate the effect of vasonatrin peptide (VNP) on the expression of C-type natriuretic peptide receptor (NPR-C) in hypoxic rat hearts.

METHODSRats were divided randomly into three groups: control group, hypoxia group(3-28 d) and VNP (25-75 microg/kg per day) + hypoxia group. The plasma concentration of atrial natriuretic peptide (ANP) in rats was measured by the means of radioimmunoassay. Furthermore, quantitative PCR was used to examine the NPR-C mRNA level in rat hearts.

RESULTSThe plasma concentration ANP in rats was significantly higher than that of control group, and VNP (75 microg/kg per day) made it more higher. Hypoxia for 3 day of had no significant effect on the NPR-C mRNA level in rat hearts, while hypoxia for 7-28 d significantly increased the level of NPR-C mRNA in a time dependent manner. VNP (50-75 microg/kg per day) significantly reduced the NPR-C mRNA level in rat hearts in a dose dependent manner.

CONCLUSIONVNP increases the plasma concentration of ANP in hypoxic rats. Hypoxia can increase expression of NPR-C in rat hearts significantly, which can be inhibited by VNP.

Animals ; Atrial Natriuretic Factor ; blood ; pharmacology ; Hypoxia ; metabolism ; Male ; Natriuretic Peptide, C-Type ; metabolism ; Natriuretic Peptides ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Atrial Natriuretic Factor ; metabolism

OBJECTIVE: To examine the expression of matrix metalloproteinase-9 (MMP-9) in human bronchial epithelial cells treated with calcitonin-gene-related peptide (CGRP). METHODS: RT-PCR and gelatin zymography were performed to examine the dynamic expression and activity of MMP-9 in human bronchial epithelial cells at different doses (10(-10), 10(-9), 10(-8), 10(-7), and 10(-6)mol/L) and different time points (6,12,18,24,36, and 48h) after the stimulation of CGRP. RESULTS: The unstimulated human bronchial epithelial cells only secreted a small amount of MMP-9. After the CGRP stimulation, the expression of MMP-9 presented in a concentration-dependent (10(-10), 10(-9), 10(-8), 10(-7), and 10(-6) mol/L) and time-dependent (6,12,18,24,36, and 48 h) manners (P<0.01) in human bronchial epithelial cells. The effect of CGRP could be diminished by H-7 and W-7, an antagonist of protein kinase C (PKC) and calmodulin (CaM) (P<0.05). CONCLUSION CGRP can stimulate the secretion and expression of MMP-9 in human bronchial epithelial cells, and the signal transduction is partly via the PKC and CaM pathway.
Bronchi ; cytology ; Calcitonin Gene-Related Peptide ; pharmacology ; Calmodulin ; metabolism ; Cells, Cultured ; Epithelial Cells ; drug effects ; metabolism ; Humans ; Matrix Metalloproteinase 9 ; metabolism ; Protein Kinase C ; metabolism ; Signal Transduction

It is reported that patients with primary hyperparathyroidism(PHPT) have disturbances in carbohydrate metabolism: in particular, hyperinsulinemia and insulin resistance are characteristic early metabolic aberrations of this disease. However, it is not clear whether changes of insulin secretion or insulin sensitivity are observed in all patients with PHPT, including those with normal glucose tolerance. Also, it is not clear whether these changes are reversible after surgical correction of PHPT. In the present study, glucose tolerance and insulin secretion were evaluated in 2 symptomatic patients with PHPT during 100g oral glucose tolerance test before and after parathyroid adenoma removal. Comparing these patients before and after surgery, glucose tolerance was not significantly different. However, C-peptide and insulin secretion was low after surgical correction of PHPT compared to the preoperative situation. This observation suggests that insulin hypersecretion in patients with PHPT precedes glucose intolerance and this early disturbance is reversible after surgery.
C-Peptide ; Carbohydrate Metabolism ; Glucose ; Glucose Intolerance ; Glucose Tolerance Test ; Humans ; Hyperinsulinism ; Hyperparathyroidism, Primary ; Insulin Resistance ; Insulin ; Parathyroid Neoplasms

OBJECTIVESTo investigate the significance of c-fos oncogene morphogenetic protein's locational expression, and the correlativity between nerve transmitters calcitonin gene-related peptide (CGRP) expression and nerve root's functional change using the animal model of the chronic compressive injury in the nerve root.

METHODSThe animal model of chronic compressive injury of the nerve root was established by transplanting autogenous cancellous bone into the intervertebral foramen. During different injury phase (1, 2, 4, 8, 12, 24 weeks after operation), the functional status of the nerve root was determined under the monitoring of evoked potential, and the expression changes of c-fos oncogene morphogenetic protein and nerve transmitter CGRP were detected using in situ hybridization technique and their expression intensity was determined using automatic image analytic instrument respectively.

RESULTSOne week after operation, the c-fos expression strengthened in both anterior and posterior root fiber obviously. Two to four weeks after operation, the expression of the posterior root fiber weakened than the anterior root fiber. After 12 weeks, the anterior root fiber expression turned down obviously, however the posterior root fiber expression backed up slightly compared with that of the 8 weeks. By the time of 24 weeks after operation, the expression enhancement in all roots disappeared. CGRP expression increased obviously at the site of compressive axon of both anterior and posterior root. The expression of the posterior root axon and ganglion cell was higher than that of the anterior root axon. CGRP expression was diminished in the second week than the first week, and that was especially obvious in the posterior root and ganglion cell. But 4 weeks after operation, the expression enhanced once more, and that was more obvious inside the anterior root axon. Eight weeks after operation, the expression intensity attained the high peak. Twelve weeks after operation, the expression started the slow-moving descent.

CONCLUSIONSThe expression of c-fos gene protein is beneficial to localize the damaged part of certain nerve. During chronic injury, the degeneration of posterior root sensory fiber is earlier than the anterior root motor fiber. The expression of CGRP strengthened when the nerve fiber degenerated by the harmful stimulation, and the expression intensity is positively related with pain. That suggests when the nervous tissue is hurt, the information of warning and regulation should be sent out to our body.

Animals ; Calcitonin Gene-Related Peptide ; metabolism ; Cats ; Disease Models, Animal ; Female ; In Situ Hybridization ; Male ; Proto-Oncogene Proteins c-fos ; metabolism ; Radiculopathy ; metabolism ; physiopathology ; Spinal Nerve Roots ; physiopathology

AIMTo study the influence of VIP on the expression of SP-A and its intracellular signal transduction pathway.

METHODSThe influence of VIP on the expression of SP-A was studied by immunohistochemistry and RT-PCR. The intracellular signal transduction pathway was further investigated by using receptor antagonist, protein kinase inhibitor and antisense oligonucleotides.

RESULTS(1) VIP(10(-8) mol/L) enhanced SP-A protein expression in alveolar type II cells (ATII) and increased the content of SP-A mRNA in lung tissue. (2) VIP receptor antagonist [D-P-C1-Phe (6)-Leu (17)]-VIP (10(-6) mol/L) could suppress the VIP-induced expression of SP-A protein and SP-A mRNA. (3) c-fos antisense oligonucleotides (9 x 10(-6) mol/L) could inhibit the VIP-induced expression of SP-A protein and SP-A mRNA. (4) Protein kinase C(PKC) inhibitor H7 (10(-5) mol/L) could also depress the V1P-induced SP-A protein and SP-A mRNA.

CONCLUSIONVIP can up-regulate the expression of SP-A through its receptor. PKC and c-fos protein play important roles in the intracellular signal transduction pathway through which VIP induces the expression of SP-A.

Animals ; Epithelial Cells ; drug effects ; metabolism ; In Vitro Techniques ; Protein Kinase C ; metabolism ; Proto-Oncogene Proteins c-fos ; metabolism ; Pulmonary Alveoli ; cytology ; Pulmonary Surfactant-Associated Protein A ; metabolism ; Rats ; Rats, Wistar ; Signal Transduction ; Vasoactive Intestinal Peptide ; pharmacology

OBJECTIVETo investigate the effects of cadmium on the levels of insulin and blood glucose in exposed workers.

METHODSNinety-eight cadmium-exposed workers in a smeltery in the mid-south district of our country were selected as the exposed subjects while the healthy doctors in the workers hospital who were not exposed to the cadmium were treated as the control. The subjects were grouped according to the exposure time, the blood cadmium and the urine cadmium. The variety of the level of serum insulin was investigated for the workers in different groups of the exposure time, the blood cadmium and the urine cadmium. The variety of the levels of the blood zinc and urine zinc were also determined. The relationships among the blood cadmium, the blood zinc and the serum insulin were analyzed.

RESULTSThe level of blood glucose in the group of the exposure time of more than 20 years [(4.9 +/- 0.6) mmol/L] was significantly higher than that in the control group [(4.6 +/- 0.60) mmol/L] with significantly statistical difference (P < 0.01). The level of serum insulin in the group of the exposure time of more than 10 years [(8.58 +/- 4.91) microIU/ml] was significantly lower than that in the control group [(11.57 +/- 5.42) microIU] with the significantly statistical difference (P < 0.05) and the level of serum insulin would be decreased significantly with the increase of the blood cadmium and urinary cadmium. The level of the urine zinc was increased significantly in the workers of the exposure time of more than 20 years. The correlation analysis indicated that the negative correlation was found between the level of serum insulin and the level of blood cadmium, as well as between the level of the serum insulin and the level of the urinary cadmium; the positive correlation was found between the level of blood glucose and the level of insulin, as well as between the level of blood glucose and the level of C peptide in serum.

CONCLUSIONThe exposure to cadmium can cause the decrease of serum insulin and may affect the level of blood glucose.

Adult ; Blood Glucose ; metabolism ; C-Peptide ; blood ; Cadmium ; metabolism ; pharmacology ; Female ; Humans ; Insulin ; blood ; Male ; Occupational Exposure ; adverse effects ; Zinc ; blood ; urine

This study was purposed to investigate the effect of knocking down eukaryotic elongation factor 1A1 (eEF1A1) gene on the proliferation and apoptosis in human acute T lymphocytic leukemia (T-ALL) cell line Jurkat and explore its mechanism. The eEF1A1 mRNA and protein expressions of Jurkat cells and 3 healthy adult peripheral blood mononuclear cells (PBMNC) were detected by real time PCR and Western blot, respectively. eEF1A1-shRNA lentivirus was constructed through molecular biological method, and was used to transfect Jurkat cells. Then, cell eEF1A1 mRNA and protein expressions were detected by real time PCR and Western blot, respectively. Cell proliferation, apoptosis and cycle were detected by MTT method, Annexin V-APC labeling and DNA ploidy analysis, respectively. Cell-related protein expressions of phosphatidylinositol-3-kinase (PI3K)/serine/threonine kinase (Akt) signaling pathway were detected by Western blot. The results showed that eEF1A1 mRNA and protein expression levels of Jurkat cells were significantly higher than that of healthy adult PBMNC, respectively (P < 0.01, P < 0.05). eEF1A1 mRNA and protein expressions of Jurkat cells were significantly knocked down by constructing eEF1A1-shRNA lentivirus. Compared to negative control group (transfected with negative control-shRNA lentivirus), cell proliferation in eEF1A1-shRNA group was significantly inhibited, cell apoptosis was remarkably induced, cell cycle was blocked in G(0)/G(1) phase, and the expression levels of p-Akt (Ser 473), nuclear factor kappa B (NF-κB), p-NF-κB (Ser 468), mammalian target of rapamycin (mTOR) and p-mTOR (Ser 2448) proteins were significantly reduced. It is concluded that eEF1A1 may be a putative oncoprotein in T-ALL cells. Knocking down eEF1A1 gene has noticeable effects on the proliferation inhibition and apoptosis induction of Jurkat cells, which may be mediated by the down-regulation of PI3K/Akt/NF-κB and PI3K/Akt/mTOR signaling pathway.
Apoptosis ; Cell Proliferation ; Gene Silencing ; Humans ; Jurkat Cells ; Peptide Elongation Factor 1 ; genetics ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction ; genetics

This study was aimed to explore the effects of expressing eukaryotic elongation factor 1A1 (eEF1A1) on proliferation and apoptosis in human acute T lymphocytic leukemia (T-ALL) cell line Jurkat with knocked down eEF1A1 gene and its mechanisms. eEF1A1-expressing lentivirus (LV) was constructed and used to transfect the Jurkat cells with knocked down eEF1A1 gene. Then, the expressions of eEF1A1 mRNA and protein were detected by real time PCR(RT-PCR) and Western blot respectively.Cell proliferation, apoptosis and cycle were detected by MTT method, Annexin V-APC labeling and DNA ploidy analysis respectively. The related protein expressions of phosphatidylinositol-3-kinase (PI3K)/serine/threonine kinase (Akt) signaling pathway were detected by Western blot. The results indicated that eEF1A1 mRNA and protein expressions of Jurkat cells with knocked down eEF1A1 gene were re-established by constructing eEF1A1-expression LV. Compared with negative control group (transfected with negative control LV and eEF1A1-shRNA LV), cell proliferation in eEF1A1 expression group was significantly enhanced, cell apoptosis was remarkably inhibited, percentage of cells in G0/G1 phase was significantly reduced alone with increased percentage of cells in S and G2/M phase, and the expression levels of p-Akt (Ser 473), nuclear factor kappa B (NF-κB), p-NF-κB (Ser 468), mammalian target of rapamycin (mTOR) and p-mTOR (Ser 2448) protein significantly increased. It is concluded that eEF1A1 may have a carcinogenic effect in T-ALL cells. eEF1A1 expression has noticeable effects on the proliferation enhancement and apoptosis inhibition of Jurkat cells, which may be mediated by the up-regulation of PI3K/Akt/NF-κB and PI3K/Akt/ mTOR signaling pathway.
Apoptosis ; Cell Proliferation ; Gene Expression ; Humans ; Jurkat Cells ; Peptide Elongation Factor 1 ; genetics ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; RNA, Small Interfering ; genetics ; Signal Transduction