ObjectiveTo study the changes of levels of α subunits of stimulatory (Gsα) and inhibitory guanine nucleotide binding protein (Giα) in newborn guinea pig (0 2 days old) myocardium undergoing global ischemic reperfusion, and influences on the changes by St.Thomas Ⅱ and cold blood cardioplegic solution.MethodsThirty newborn guinea pigs were randomly assigned to three groups. GroupⅠ ( n = 10): the newborn hearts suffered by hypothermic global ischemia; group Ⅱ( n =10): the newborn hearts arrested by St. Thomas Ⅱ , and group Ⅲ ( n = 10): the newborn hearts arrested by cold blood cardioplegic solution. Levels of Gsα and Giα were investigated with Western blot analysis.ResultsNo differences of levels of Gsα and Giα were found in three groups before ischemia ( P gt;0.05). The level of Gsα after ischemia was significantly decreased than before ischemia in groupⅠand group Ⅱ ( P lt; 0 01), whereas no pronounced changes in group Ⅲ ( P gt;0.05) were noted after ischemia. The level of Gsα in group Ⅲ was not significantly changed after reperfusion compared with before ischemia( P gt;0 05), and it was much higher than those in groupⅠand group Ⅱ ( P lt; 0 01). Level of Giα was found not markedly changed in group Ⅲ after reperfusion compared with that before ischemia, but was notable higher in groupⅠand group Ⅱ( P lt;0.01). ConclusionsSignificant decrease of level of Gsα, whereas marked increase of level of Giα are found in myocardium of newborn guinea pig undergoing hypothermic (20℃) ischemic reperfusion. No impact of St. Thomas Ⅱ on these changes is verified, but recovery to the level of Gsα and Giα before ischemia is achieved by cold blood cardioplegic solution after ischemia and reperfusion. Unbalance between Gsα and Giα is the one of the mechanisms of ischemic reperfusion injury for immature myocardium.
ObjectiveTo investigate the protective effect and the regulation mechanism of oxaloacetate (OAA) on myocardial ischemia reperfusion injury in rats. MethodsSixty rats, weight ranged from 200 to 250 grams, were randomly divided into 6 groups:a negative control group, a sham operation control group, a model control group, an OAA pretreatment myocardial ischemia-reperfusion model group (three subgroups:15 mg/kg, 60 mg/kg, 240 mg/kg). We established the model of myocardial ischemia reperfusion of rats and recorded the internal pressure of left ventricle (LVSP), the maximal rate of left ventricular pressure change (±dp/dtmax) and left ventricular end diastolic pressure (LVEDP). We restored reperfusion 180 minutes after ligating the left anterior descending coronary artery 30 minutes and determinated cardiac troponin Ⅰ (cTn-I), lactate dehydrogenase (LDH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px). We took out heart tissues, stained it and calculated the infarcted size. We used the Western blot to detect the expression of NF-E2 related factor 2 (Nrf2), Kelch-like ECH-associated protein-1 (Keap1) and heme oxygenase-1 (HO-1). ResultsCompared with the sham operation group, heart function indexes in the negative control group had no significant difference (P>0.05). But in the model control group there was a decrease (P<0.05) And the serum levels of LDH, cTn-I, and myocardial infarcted size were significantly increased (P<0.01). Compared with the model control group, heart function indexes in the OAA pretreatment groups improved, the serum LDH, cTn-I activity, and infarct size decreased (P<0.05), SOD and GSH-Px activity increased (P<0.05). And these results were statistically different (P<0.01) in the high dose OAA pretreatment groups. Compared with the model control group, the expression of Keap1 in the OAA pretreatment group was down-regulated (P<0.001) while total Nrf2, nucleus Nrf2 and its downstream HO-1 was up-regulated (P<0.001), which suggested that OAA enhanced antioxidant capacity by (at least in part) Keap1-Nrf2 pathway, resulting in reducing myocardial damage and protecting myocardium after acute myocardial ischemia reperfusion injury. ConclusionOxaloacetate can provide protective effects on myocardial ischemia reperfusion injury through down-regulating the expression of Keap1 and up-regulating the expression of Nrf2 and its downstream peroxiredoxins to improve antioxidant capacity.
ObjectiveTo investigate the effect of cytoskeleton modification on the adipogenic differentiation of rat Achilles-derived tendon stem cells (TSCs) in vitro. MethodsTSCs were isolated from the tendon tissue of male Sprague Dawley rats (aged 3 weeks) by enzymatic digestion method and cultured for 3 passages. After the 3rd passage cells were cultured with DMEM medium containing 15% fetal bovine serum and cytochalasin D (CYD) at the concentrations of 0, 50, 100, 500, and 1 000 ng/mL, the cell survival condition and morphology changes were observed by inverted phase contrast microscope, the cytoskeleton was observed through fibrous actin (F-actin) staining, and the ratio of F-actin/soluble globular actin (G-actin) was detected and calculated through Western blot. According to the above results, the effective concentration of CYD was selected and used for next experiments. After TSCs were cultured for 3 and 7 days respectively with adipogenic induction media (induction group), adipogenic induction media containing CYD (CYD+induction group), ordinary medium (ordinary group), and ordinary medium containing CYD (CYD+ordinary group), the real-time quantitative PCR (qRT-PCR) and Western blot were carried out to measure the mRNA and protein expressions of adipogenic differentiation-related markers, including peroxisome proliferator-activated receptor γ (PPARγ), 1ipoprotein lipase (LPL), and fatty acid binding protein (aP2). ResultsThe final CYD concentration of 100 ng/mL can inhibit effectively G-actin polymerization into F-actin, but could not affect TSCs survival, which was used for next experiments. qRT-PCR and Western blot suggested that the mRNA expressions of PPARγ, LPL, and aP2 and the protein expressions of PPARγ and aP2 were increased significantly in the CYD+induction group at 3 and 7 days when compared with the induction group (P<0.05). In the CYD+ordinary group, there still was a significant increase in the mRNA expressions of PPARγ, LPL, and aP2 when compared with the ordinary group (P<0.05). ConclusionInhibition of F-actin polymerization can increase adipogenic differentiation of rat Achilles-derived TSCs in vitro, and cytoskeleton modification is a pre-requisite for TSCs differentiation into adipocytes, which might have important implications for the mechanism research of tendinopathy.
Objective To systemically review the effectiveness and safety of human recombinant activated protein C (rhAPC) for severe sepsis. Methods Such databases as MEDLINE, EMbase, The Cochrane Library, VIP, CNKI and CBM were electronically searched for comprehensively collecting randomized controlled trials (RCTs) on the effectiveness and safety of human recombinant activated protein C (rhAPC) for severe sepsis from inception to July 2012. References of included studies were also retrieved. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of included studies. Then, meta-analysis was performed using RevMan 5.0 software. Results Totally, five RCTs involving 6 307 patients were included. The results of meta-analysis showed that, no significant difference was found in 28-day mortality (RR=1.00, 95%CI 0.84 to 1.19, P=1.00) and 90-day mortality (RR=1.00, 95%CI 0.87 to 1.14, P=0.96) between the rhAPC group and the placebo group. The results of subgroup analysis showed that, the two groups were similar in the 28-day mortality of patients with different Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (APACHE II scorelt;25: RR=1.06, 95%CI 0.93 to 1.21, P=0.37; APACHE II score≥25: RR=0.93, 95%CI 0.69 to 1.24, P=0.60), and in the 28-day mortality by protein C deficiency class (APC deficiencylt;80%: RR=0.96, 95%CI 0.56 to 1.65, P=0.89; APC deficiencygt;80%: RR=0.61, 95%CI 0.34 to 1.08, P=0.09). Besides, bleeding risk in the rhAPC group was 1.62 fold more than that in the placebo group (RR=1.62, 95%CI 1.17 to 2.23, P=0.004). No significant difference was found in the incidence of adverse reaction (RR=1.04, 95%CI 0.92 to 1.18, P=0.53). Conclusion Current evidence suggests that, rhAPC could not improve the prognosis of patients with severe sepsis, but it significantly increases bleeding risk.
Objective To systematically review the effectiveness and safety of intracoronary glycoprotein IIb/IIIa inhibitors (GPIs) undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) compared with intravenous administration. Methods Databases including PubMed, EMbase, The Cochrane Library (Issue 9, 2012), Ovid, CBM, CNKI and VIP were electronically searched for randomized controlled trials (RCTs) about intracoronary GPIs administration versus intravenous administration undergoing PCI for ACS from inception to September 30th, 2012. Meanwhile, domestic relevant papers published in recent 1 year were also retrieved manually. References of the included studies were retrieved, too. According to the inclusion and exclusion criteria, two reviewers independently screened literature, extracted data, and assessed the methodologically quality of the included studies. Then, meta-analysis was performed using RevMan 5.1 software. Results 10 RCTs involving 3 553 ACS patients were finally included. The results of meta-analysis showed that: compared with intravenous administration, intracoronary GPIs administration decreased the major adverse cardiovascular event (MACE) (OR=0.54, 95%CI 0.34 to 0.85, P=0.008). The incidences of re-infarction (MI), revascularization (TVR) and heart failure were (OR=0.62, 95%CI 0.39 to 0.97, P=0.04), (OR=0.59, 95%CI 0.36 to 0.97, P=0.04), (OR=0.52, 95%CI 0.32 to 0.84, P=0.008), respectively. But for the mortality, there were no significant differences between the two groups (OR=0.81, 95%CI 0.58 to 1.14, P=0.23). Intravenous administration and intracoronary administration were alike in the incidences of mild/serious bleeding (mild: OR=0.94, 95%CI 0.75 to 1.19, P=0.63; serious: OR=1.18, 95%CI 0.76, 1.84, P=0.47). Conclusion Compared with routine GPIs regimen of intravenous bolus, intracoronary administration with initial dosage showed significant benefits in clinical outcomes in ACS patients undergoing PCI, which could not increase the incidence of bleeding.
Objective To investigate the correlation between glycosylated hemoglobin A1c (HbA1c) and severity of coronary artery lesions in young men with acute myocardial infarction (AMI). Methods Total 278 young men with AMI less than 45 years old were retrospectively studied, and all of them were admitted to hospital from January 2009 to December 2011, and had undergone coronary angiography. According to the results of coronary angiography, the patients were divided into three groups based on the number of artery lesions: the single group (156 cases), the double group (64 cases) and the triple group (58 cases). The relationship between the severity of coronary artery lesions and the following factors were observed: HbA1c, systolic blood pressure (SBP), diastolic blood pressure (DBP), hemoglobin (Hb), serum uric acid (UA), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), body mass index (BMI), smoking history, drinking history and family history of early coronary artery disease. Results a) HbA1c levels were gradually raised in all the three groups, but the single group (6.39±1.67%) was significantly lower than the double group (6.91±1.63%) and the triple group (7.41±2.12%), with significant differences (Plt;0.05); the HbA1c level of the single group was significantly lower than the triple group in both the ST-segment elevation AMI (6.42±1.68% vs. 7.17±1.86%, Plt;0.05) and the non-ST-segment AMI (5.57±0.37% vs. 8.56±2.83%, Plt;0.05); the HbA1c level of the single group was significantly lower than the triple group in patients with diabetes millitus (8.31±1.83% vs. 8.59±2.02%, Plt;0.05) and in patients without diabetes millitus (5.56±0.33% vs. 5.74±0.37%, Plt;0.05); b) There were significant differences in SBP, TC, HDL-C, LDL-C and drinking history between the single group and the other two groups (all Plt;0.05), and there were significant differences in DBP and TG between the single group and the double group (all Plt;0.05); and c) The results of logistic regression analysis showed that, LDL-C (OR=1.790), HbA1c (OR=1.287) and SBP (OR=1.042) were the independent risk factors (all Plt;0.05) for multiple lesions in coronary arteries of young men with AMI. Conclusion Glycosylated hemoglobin A1c is an independent risk factor for multiple lesions in coronary arteries of young men with AMI.
Objective To evaluate the clinical application of Hb-A2 detection of thalassemia including-alpha-thalassemia and beta-thalassemia. Methods There were 70 Southeast Asia type alpha-thalassemia heterozygosity and 43 normal gene type resulted from Gap-PCR, and 33 beta-thalassemia heterozygosity and 36 normal gene type diagnosed by reverse dot blot (RDB). Cutoff value of Hb-A2 in finding of alpha-thalassemia and beta-thalassemia was present.The sensitivity, specificity, positive and negative likelihood ratio, and receiver operator characteristic curve (ROC) were used to evaluate the significance of Hb-A2 level in screening thalassemia in adults. Results The borderline values between normal and pathological range of Hb-A2 were ≤2.6% in alpha-thalassemia and ≥3.8% available in beta-thalassemia. Sensitivity and specificity were 59% and 54% in alpha-thalassemia, 76% and 83% in beta-thalassemia, respectively. ROC showed that the area covered beneath the curve of beta-thalassemia was more than that of alpha-thalassemia. Conclusions The cutoff between normal and pathological range of Hb-A2 is ≤2.3% in alpha-thalassemia and ≥3.8% in beta-thalassemia. Hb-A2 detection has higher sensitive and specific in beta-thalassemia diagnosis, but lower in alpha-thalassemia diagnosis.
ObjectiveTo investigate the association between polymorphism of V4,F+1 in ADAM33 (adisintegrin and metalloproteinase 33) gene and COPD in a northwestern Uighur population. MethodsA total of 100 Uighur COPD patients and 140 healthy volunteers were recruited in the study. Genotypes were determined by restriction fragment lengthpolymorphism(PCR-RFLP). All subjects had a epidemiological investigation including modified british medical research council(mMRC),COPD assessment test(CAT),and pulmonary function test. The 100 Uighur COPD patients were assessed by revised GOLD2011. ResultsAssessed by revised GOLD2011,the patients of A,B and C grade accounted for 22%,35% and 30%,respectively. There was no statistical significance in the distributions of the V4,F+1 alleles between the patients and the controls(P>0.05). There was no statistical significance between SNPs in ADAM33(V4 and F+1) with the decreased lung function and the grade of COPD(P>0.05). ConclusionThere was no association between polymorphism of V4,F+1 in ADAM33 gene and COPD in a northwestern Uighur population.
目的 通过检测脑胶质瘤患者血清中胰岛素生长因子-1（IGF-1）和胶质纤维酸性蛋白（GFAP）的表达，探讨其与胶质瘤分级及预后评估的关系。 方法 2010年12月－2011年11月，采用双抗体一步夹心法分别测定A、B两组共40例不同级别脑胶质瘤患者术前、术后血清中IGF-1和GFAP浓度。 结果 高级别胶质瘤患者组血清中IGF-1浓度显著高于低级别胶质瘤组（P=0.009 0）；血清GFAP浓度显著低于低级别胶质瘤组（P＜0.000 1）。经手术治疗后且疗效评价为有效的胶质瘤患者，其血清中IGF-1、GFAP浓度较术前水平显著下降（P＜0.001 0）。结论 IGF-1、GFAP是两种较好的脑胶质瘤血清标志物，在其分级及预后评估中具有重要的临床应用价值。