Relationships between PON1 Q192R polymorphism and clinical outcome of antiplatelet treatment after percutaneous coronary intervention: a meta-analysis

This meta-analysis was performed to assess the relationships between the PON1 Q192R (rs662 T>C) polymorphism and the clinical outcome of antiplatelet treatment after percutaneous coronary intervention (PCI). A range of electronic databases were searched: Web of Science (1945–2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966–2013), EMBASE (1980–2013), CINAHL (1982–2013) and the Chinese Biomedical Database (CBM) (1982–2013) without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. The crude odds ratio (OR) with their 95 % confidence interval (CI) were calculated. Six clinical cohort studies with a total number of 5,189 patients undergoing PCI for coronary heart disease were included. Our meta-analysis revealed that the PON1 Q192R polymorphism was correlated with an increased risk of major adverse cardiovascular events (MACE) in patients receiving antiplatelet treatment after PCI (C allele vs. T allele: OR = 1.22, 95 % CI 1.04–1.43, P = 0.014; CT+CC vs. TT: OR = 1.38, 95 % CI 1.03–1.86, P = 0.029; CC vs. TT: OR = 1.45, 95 % CI 1.05–1.99, P = 0.024; respectively), especially among Asians. Furthermore, we found significantly positive correlations between the PON1 Q192R polymorphism and the incidence of stent thrombosis in patients receiving antiplatelet treatment after PCI (C allele vs. T allele: OR = 1.42, 95 % CI 1.08–1.87, P = 0.011; CT+CC vs. TT: OR = 1.93, 95 % CI 1.01–3.67, P = 0.046; CC vs. TT: OR = 2.18, 95 % CI 1.09–4.35, P = 0.027; respectively). Our meta-analysis of clinical cohort studies provides evidence that the PON1 Q192R polymorphism may increase the risk of MACE and stent thrombosis in patients receiving antiplatelet treatment after PCI.     

Effect of statins on coronary blood flow after percutaneous coronary intervention in patients with stable coronary artery disease

Aims

Statins have favourable effects on the vascular system. However, few data are available regarding the effect of these drugs on patients undergoing percutaneous coronary intervention (PCI). We sought to determine the impact of prior statin use on coronary blood flow after PCI in patients with stable coronary artery disease (CAD) by using the corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC).

Methods

A total of 80 consecutive eligible patients (mean age: 60 ± 7 years, 65?% male) with the diagnosis of stable CAD who were hospitalised for elective PCI were retrospectively enrolled in our study. The study population was divided into two groups according to statin use at least 6 months before PCI. Group 1 comprised of 51 patients (67?% male; mean age: 58 ± 4 years) taking statins and group 2 comprised of 29 patients (62?% male; mean age: 60 ± 3 years) not taking statins. PCI was applied to de novo type A lesions. CTFC was calculated for the treated vessels at baseline and after PCI.

Results

The two groups had similar characteristics in terms of age, sex, concomitant medications, lesion characteristics, pre-procedural CTFC, lipid parameters, and risk factors for CAD. Post-PCI CTFC (16 ± 3 vs. 22 ± 5, p = 0.01) and hs-CRP (2.1 ± 0.7 mg/l vs. 6.1 ± 2 mg/l, p = 0.01) in patients receiving statins before PCI were significantly lower than in patients without statin therapy. Multiple logistic regression analysis showed that statin pre-treatment (OR 2.5, 95?% CI 1.2 to 3.8, p < 0.001) and hs-CRP level (OR 1.8, 95?% CI 1.2 to 2.4, p = 0.001) were independent predictors of post-PCI CTFC.

Conclusions

In patients with stable CAD undergoing PCI, receipt of long-term statin therapy was associated with improvement in epicardial perfusion after PCI.

     

Comparison of Short- and Medium-Term Clinical Outcomes between Transradial Approach and Transfemoral Approach in a High-Volume PCI Heart Center in China

Background

Transradial approach (TRA) outweighed transfemoral approach (TFA) in acute coronary syndrome patients because the former has better short-term outcomes in high-volume percutaneous coronary intervention (PCI) centers. Our study was one of the limited studies specifically in comparing the short- and medium-term effects of TRA and those of TFA in patients undergoing elective PCIs.

Methods

A total of 21,242 patients who underwent elective PCI with stent implantation were included. Using propensity score methodology, 1,634 patient pairs were matched. Major clinical outcomes and PCI-related complications between TRA and TFA were compared.

Results

In the propensity score-matched patients, the rates of in-hospital net adverse clinical events, which included death, myocardial infarction (MI), target vessel revascularization (TVR), stroke, and major bleeding, were much lower with TRA than with TFA (1.8% vs. 3.9%, P < 0.001). This difference was mainly due to the lower rate of major bleeding (0.6% vs. 1.8%, P < 0.001) and the decreased rate of MI (1.1% vs. 1.9%, P = 0.060). PCI-related dissection and thrombosis were similar between the TRA and TFA groups (both P > 0.05). Meanwhile, one-year incidence rates of major adverse cardiovascular events, which included death, MI, and TVR, were also similar (4.1% vs. 4.9%, P = 0.272) in TRA and TFA. Multivariable regression analyses showed that TRA was an independent predictor of the low rate of in-hospital net adverse clinical events (odds ratio, 0.53; 95% confidence interval, 0.40 to 0.71), but not of major adverse cardiovascular events at one-year follow-up (hazard ratio, 1.01; 95% confidence interval, 0.96 to 1.06).

Conclusions

In patients undergoing elective PCI, TRA patients had lower rates of in-hospital net adverse clinical outcomes compared with TFA patients. TRA might be recommended as a routine approach in high-volume PCI hospitals for elective PCIs.     

Effects of Ezetimibe on Endothelial Progenitor Cells and Microparticles in High-Risk Patients

Imbalance on endothelial turnover can predict cardiovascular outcomes. We aimed at evaluating the effects of lipid-modifying therapies on circulating endothelial progenitor cells (EPCs), endothelial microparticles (EMPs), and platelet microparticles (PMPs) in high cardiovascular risk subjects with elevated C-reactive protein (CRP). Sixty-three individuals with coronary heart disease (CHD) or CHD risk equivalent on stable statin therapy, with LDL-cholesterol <100 mg/dL and CRP ≥2.0 mg/L were selected. After a 4-week run-in period with atorvastatin 10 mg, those with persistent CRP ≥2.0 mg/L were randomized to another 4-week treatment period with atorvastatin 40 mg, ezetimibe 10 mg or atorvastatin 40 mg/ezetimibe 10 mg. EPC (CD34⁺/CD133⁺/KDR⁺), EMP (CD51⁺), and PMP (CD42⁺/CD31⁺) were quantified by flow cytometry. Atorvastatin 40 mg and atorvastatin 40 mg/ezetimibe 10 mg reduced LDL-cholesterol (P < 0.001, paired T test, vs. baseline). Combined therapy, but not ezetimibe reduced CRP. CD34⁺/KDR⁺ EPC were reduced after ezetimibe alone (P = 0.011 vs. baseline, Wilcoxon test) or combined with atorvastatin (P = 0.016 vs. baseline, Wilcoxon test). In addition, ezetimibe increased CD51⁺ EMP (P = 0.017 vs. baseline, Wilcoxon test). No correlations between these markers and LDL-cholesterol or CRP were observed. These results contribute to understand the link between inflammation and vascular homeostasis and highlight the broader benefit of statins decreasing inflammation and preventing microparticles release, an effect not observed with ezetimibe alone.     

Changes of Plasma B-Type Natriuretic Peptide Levels after High-Pressure Post-Dilation following Coronary Stent Deployment

Objective

To evaluate the changes of plasma B-type natriuretic peptide(BNP) levels after high-pressure post-dilation following coronary stent deployment.

Methods

A total of 173 patients undergoing percutaneous coronary intervention for the left anterior descending artery were enrolled into the study. All patients were divided into two groups: the conventional group and the post-dilation group. The plasma BNP, troponin I(TnI), myocardial band isoenzyme of creatine kinase(CK-MB) levels and the serum high sensitive C-reactive protein(hs-CRP) levels immediately before and 24 hours after the interventional procedures were compared between the two groups.

Results

There were no significant differences between the two groups in terms of clinical features, clinical and biochemical parameters, stent parameters, pre-procedural plasma BNP and TnI levels, pre-procedural serum hs-CRP levels, as well as pre- and post-procedural CK-MB levels (all P>0.05). In the conventional group, post-procedural plasma BNP levels were significantly reduced when compared with the pre-procedural levels, median(25th,75th) were 32.5 ng/L(15.0,52.4) vs. 37.7 ng/L(18.2,67.3), P = 0.001. In the post-dilation group, post-procedural plasma BNP levels were significantly increased when compared with the pre-procedural levels, median(25th,75th) were 53.5 ng/L(29.6,82.8) vs. 44.2 ng/L(17.15,70.7), P<0.0001. Post-procedural plasma TnI levels were also significantly increased when compared with the pre-procedural levels in both groups, median(25th,75th) were 0.02 ng/L(0.01,0.08) vs. 0.01 ng/L(0.01,0.01), 0.05 ng/L(0.01,0.35) vs. 0.01 ng/L(0.01,0.01), respectively, P<0.0001, so were the serum hs-CRP levels, median(25th,75th) were 3.3 mg/L(2.4,4.7) vs. 2.2 mg/L(1.4,3.3), 4.2 mg/L(3.175,5.825) vs. 2.3 mg/L(1.45,3.6), respectively, P<0.0001. Post-procedural plasma BNP, TnI and serum hs-CRP levels in the post-dilation group were significantly higher than those in the conventional group(all P<0.0001).

Conclusion

High-pressure post-dilation following coronary stent deployment resulted in a significant increase of plasma BNP levels, as well as plasma TnI levels and serum hs-CRP levels, which may be related to myocardial perfusion, more myocardial injury and more inflammation.     

Impact of neutrophil-to-lymphocyte ratio on periprocedural myocardial infarction in patients undergoing non-urgent percutaneous coronary revascularisation

Background

Pro-thrombotic conditions importantly influence myocardial perfusion and procedural results after percutaneous coronary intervention (PCI). The neutrophil-to-lymphocyte ratio (NLR) has emerged as a predictor of cardiovascular events and of long-term prognosis, especially in ST-elevation myocardial infarction patients undergoing primary PCI. The aim of our study was to evaluate the role of NLR on periprocedural myocardial infarction (MI) in patients undergoing non-urgent PCI.

Methods

In a consecutive cohort of 1542 patients undergoing PCI, myonecrosis biomarkers were determined at 6, 12, 24 and 48 hours post-procedure. Patients were divided into quintiles according to NLR values. Periprocedural myonecrosis was defined as a troponin I increase of 3 times the upper limit of normal or as 50?% of an elevated baseline value, whereas periprocedural MI was defined as a CK-MB increase of 3 times the upper limit of normal or 50?% of baseline.

Results

Higher NLR was related to age, established risk factors and cardiovascular history. NLR was associated with severe coronary artery disease (p = 0.009), tighter stenosis (p < 0.001), coronary calcifications (p = 0.005), intracoronary thrombus or thrombectomy use (p < 0.001), TIMI flow pre- and post-PCI (p < 0.001), and inversely to restenosis (p = 0.04) and use of a drug-eluting stent (p = 0.001). NLR did not influence the occurrence of myonecrosis (p = 0.75; adjusted OR (95?% CI) = 0.99 (0.63–1.54), p = 0.96), but was associated with a higher occurrence of periprocedural MI, even after correction for baseline differences (p = 0.03; adjusted OR (95?% CI) = 1.33 (1.02–2.3), p = 0.02), with NLR ≥ 3 best predicting the risk of periprocedural MI at the receiver operating characteristic curve analysis.

Conclusion

In patients undergoing non-urgent PCI, a higher NLR increases the risk of periprocedural MI, especially for values ≥ 3.

     

Continous Epidural Butorphanol Decreases the Incidence of Intrathecal Morphine-Related Pruritus After Cesarean Section: A Randomized,Double-Blinded,Placebo-Controlled Trial

This randomized, double-blinded, placebo-controlled trial investigated the effect of continuous epidural butorphanol on intrathecal morphine-related pruritus in patients undergoing cesarean section. Eighty-three patients undergoing elective cesarean section under spinal anesthesia (1.5 mL of isobaric bupivacaine 0.5 % and 0.1 mg of preservative-free morphine) were enrolled in this study. Subjects were randomized to receive epidural butorphanol (n = 43) or normal saline combined bupivacaine (n = 40). In the study group, after the umbilical cord was clamped, patients were administered an epidural loading dose of 1 mg followed by a 48-h infusion of 0.004 % butorphanol with 0.1 % bupivacaine at a rate of 2 mL/h. In the normal saline group, saline was used for the loading dose and the infusion 0.1 % bupivacaine at a same rate. Postoperatively, a blinded observer recorded the incidence/severity of pruritus, visual analog pain scores and sedation level at 1, 3, 6, 9, 12, 24 and 48 h. The 48-h consumption of breakthrough analgesic (tramadol) was also noted. The primary outcome was the incidence of pruritus at 48 h. At 48 h, the incidence of pruritus was significantly lower in the butorphanol group (16.3 vs. 52.5 %; P < 0.001). Furthermore, compared with the normal saline group, the intensity of pruritus was also decreased with epidural butorphanol at 3, 6 and 9 h (all P ≤ 0.008). The pain scores were significantly lower at 12, 24 and 48 h (all P < 0.05) in the butorphanol groups. Patients only receiving bupivacaine required a higher cumulative dose of tramadol (37.5 ± 62.8 vs. 9.3 ± 36.6; P = 0.014). In patients undergoing elective cesarean section, continuous epidural butorphanol with bupivacaine decreases the incidence and severity of intrathecal morphine-related pruritus without adversely affecting the quality of postoperative analgesia.     

Reduced number of cardiovascular events and increased cost-effectiveness by genotype-guided antiplatelet therapy in patients undergoing percutaneous coronary interventions in the Netherlands

Aim

This study explores clinical outcome in cytochrome P450 2C19 (CYP2C19)-related poor metaboliser patients treated with either clopidogrel or prasugrel after percutaneous coronary intervention (PCI) and investigates whether this could be cost-effective.

Methods and results

This single-centre, observational study included 3260 patients scheduled for elective PCI between October 2010 and June 2013 and followed for adverse cardiovascular events until October 2014. Post PCI, CYP2C19 poor metaboliser patients were treated with clopidogrel or prasugrel, in addition to aspirin. In total, 32 poor metabolisers were treated with clopidogrel and 41 with prasugrel. The number of adverse cardiovascular events, defined as death from cardiovascular cause, myocardial infarction, stent thrombosis, every second visit to the catheterisation room for re-PCI in the same artery, or stroke, within 1.5 years of PCI, was significantly higher in the CYP2C19 poor metaboliser group treated with clopidogrel (n = 10, 31?%) compared with the poor metaboliser group treated with prasugrel (n = 2, 5?%) (p = 0.003). Costs per gained quality-adjusted life years (QALY) were estimated, showing that genotype-guided post-PCI treatment with prasugrel could be cost-effective with less than € 10,000 per gained QALY.

Conclusion

This study provides evidence that for CYP2C19-related poor metabolisers prasugrel may be more effective than clopidogrel to prevent major adverse cardiovascular events after PCI and this approach could be cost-effective.

     

替罗非班联合尼可地尔对急诊PCI患者心功能和短期预后的影响

目的:探讨急诊PCI患者在联合使用替罗非班和尼可地尔后对心功能和短期预后的影响。方法:入选98例接受急诊PCI的AMI患者随机分为对照组(n=49)和联合治疗组(n=49)。对照组单纯给予替罗非班治疗,联合治疗组在对照组基础上给予尼可地尔5 mg tid口服治疗。观察记录两组患者治疗8周前后LVEF、NT-pro BNP水平,并随访MACE事件发生情况。结果:两组患者在治疗前LVEF及NT-pro BNP水平比较没有统计学差异(P0.05)。在治疗8周后联合治疗组和对照组LVEF及NT-pro BNP水平均较治疗前水平明显改善(P0.05)。治疗8周后联合治疗组患者LVEF及NT-pro BNP水平明显优于对照组患者(P0.05)。经过8周的治疗,联合治疗组再次发生心绞痛事件(6.12%VS 24.49%,P=0.025)、恶性心律失常(2.04%VS 16.33%,P=0.036)和心力衰竭事件(2.04%VS 18.37%,P=0.020)明显低于对照组。结论:替罗非班联合尼可地尔可进一步改善急诊PCI患者心功能及短期预后,值得临床推广。     

Reduced expression of aquaporin 9 in tubal ectopic pregnancy

Previous studies demonstrate significant roles for passive water channels (aquaporins, AQPs) in maintaining water homeostasis in cell membranes of endometrial cells during decidualisation and embryo implantation. However, there is little information regarding the role of AQPs in the human fallopian tube, specifically their role in human tubal ectopic pregnancy. In this study we took tissue samples from the site of implantation of tubal ectopic pregnancy (group 1, N = 30, mean age 32 years, range 23–42) and the corresponding non-implantation site in women undergoing salpingectomy for tubal pregnancy (group 2). Ampullary fallopian tubes during mid-secretory phase were collected as control group (group 3, N = 17, mean age 37 years, range 30–50). Thin sections were prepared and stained with anti-AQP9, and, for estrogen and progesterone receptors in each group. Immunohistochemical studies showed that AQP9 proteins localize in the cytoplasm of epithelial cells of Fallopian tube. Expression of AQP9 was significantly reduced during tubal pregnancy compared to controls (group 1 vs. group 3, P = 0.036; group 2 vs. group 3, P = 0.029), and, this reduced expression was not related to estrogen receptor or progesterone receptor status (group 2, ER vs. AQP9, Pearson r = 0.173, P = 0.361; PR vs. AQP9, Pearson r = 0.124, P = 0.514, respectively). Similarly, there is no correlation between AQP9 and estrogen receptor or progesterone receptor status in the normal group (group 3, ER vs. AQP9, Pearson r = ?0.026, P = 0.923; PR vs. AQP9, Pearson r = ?0.292, P = 0.255, respectively). Reduced expression of AQP9 in human fallopian tube may contribute to aspects of pathophysiology of tubal ectopic pregnancy.     

The plant histaminase: a promising enzyme with antioxidant properties versus histamine release in isoprenaline-induced myocardial infarction in rats

The present study was designed to evaluate possible protective effects of purified histaminase from Lathyrus sativus L. seedling on the myocardial injuries upon isoprenaline-induced myocardial infarction in rats. In this regard, blood histamine concentration, creatine kinase-MB (CK-MB) activity, antioxidant status, and histopathological changes of the hearts were measured. A total of 40 adult male Sprague–Dawley rats were divided into five equal groups and treated in the following order: control (normal saline), isoprenaline (isoproterenol 110 mg/kg BW), Isopren.-H₁ (isoprenaline plus histaminase 80 U/kg BW), Isopren.-H₂ (isoprenaline plus histaminase 120 U/kg BW), and Isopren.-H₃ (isoprenaline plus histaminase 160 U/kg BW). Myocardial infarction was manifested by a significant elevation in the level of CK-MB and histopathological findings in isoprenaline group when compared to controls. In contrast, histaminase pretreatment at dose of 160 U/kg prevented isoprenaline-induced histamine release and significantly decreased CK-MB activity as well as histopathological changes in Isopren.-H₃ group. A significant increase in the catalase (CAT) and superoxide dismutase (SOD) activities was also observed by histaminase treatment in Isopren.-H₂ and Isopren.-H₃ groups. Although the activity of glutathione peroxidase (GPx) increased significantly to suppress oxidative stress in isoprenaline group, it was not able to prevent lipid peroxidation (as shown by TBARS concentration) in the heart of rats. In conclusion, the plant-originated histaminase presented as a promising enzyme with antioxidant properties against histamine release and myocardial infarction in rats, and it seems be a suitable therapeutic agent for future clinical trials in humans.     

Synergic Effect of Exercise and Lipoic Acid on Protection Against Kainic Acid Induced Seizure Activity and Oxidative Stress in Mice

Anti-convulsant effects of physical exercise and lipoic acid (LA), also referred to as thioctic acid with antioxidant activity, were investigated using chemical induced seizure model. We investigated the synergic effect of physical exercise and LA on kainic acid-induced seizure activity caused by oxidative stress. After 8 weeks of swimming training, body weight decreased and endurance capacity increased significantly compared to sedentary mice. Kainic acid (30 mg/kg, i.p.) evoked seizure activity 5 min after injection, and seizure activity peaked approximately 80 min after kainic acid treatment. Median seizure activity score in KA only treated group was 4.55 (range 0.5–5), 3.45 for “LA + KA” group (range 0.5–4.3), 3.12 for “EX + KA” group (range 0.05–3.4, p < 0.05 vs. “KA only” group), 2.13 for “EX + LA + KA” group (range 0.5–3.0, p < 0.05 vs. “EX + KA” group). Also, there was a synergic cooperation of exercise and LA in lowering the mortality in kainic acid treated mice (χ² = 5.45, p = 0.031; “EX + KA” group vs. “LA + EX + KA” group). In addition, the synergic effect of exercise and LA was found in PGx activity compared to separated treatment (“LA + EX + KA”: 37.3 ± 1.36; p < 0.05 vs. “LA + KA” and “EX + KA” group). These results indicate that physical exercise along with LA could be a more efficient method for modulating seizure activity and oxidative stress.     

Magnesium Supplementation and the Effects on Wound Healing and Metabolic Status in Patients with Diabetic Foot Ulcer: a Randomized,Double-Blind,Placebo-Controlled Trial

Hypomagnesemia is associated with the development of neuropathy and abnormal platelet activity, both of which are risk factors for diabetic foot ulcer (DFU). This study was carried out to evaluate the effects of magnesium administration on wound healing and metabolic status in subjects with DFU. This randomized, double-blind, placebo-controlled trial was performed among 70 subjects with grade 3 DFU. Subjects were randomly divided into two groups (35 subjects each group) to receive either 250 mg magnesium oxide supplements or placebo daily for 12 weeks. Pre- and post-intervention wound depth and appearance were scored in accordance with the “Wagner-Meggitt’s” wound assessment tool. Fasting blood samples were taken at baseline and after the 12-week intervention to assess related markers. After the 12-week treatment, compared with the placebo, magnesium supplementation resulted in a significant increase in serum magnesium (+0.3 ± 0.3 vs. ?0.1 ± 0.2 mg/dL, P < 0.001) and significant reductions in ulcer length (?1.8 ± 2.0 vs. ?0.9 ± 1.1 cm, P = 0.01), width (?1.6 ± 2.0 vs. ?0.8 ± 0.9 cm, P = 0.02), and depth (?0.8 ± 0.8 vs. ?0.3 ± 0.5 cm, P = 0.003). In addition, significant reductions in fasting plasma glucose (?45.4 ± 82.6 vs. ?10.6 ± 53.7 mg/dL, P = 0.04), serum insulin values (?2.4 ± 5.6 vs. +1.5 ± 9.6 μIU/mL, P = 0.04), and HbA1c (?0.7 ± 1.5 vs. ?0.1 ± 0.4%, P = 0.03) and a significant rise in the quantitative insulin sensitivity check index (+0.01 ± 0.01 vs. ?0.004 ± 0.02, P = 0.01) were seen following supplementation of magnesium compared with the placebo. Additionally, compared with the placebo, taking magnesium resulted in significant decrease in serum high-sensitivity C-reactive protein (hs-CRP) (?19.6 ± 32.5 vs. ?4.8 ± 11.2 mg/L, P = 0.01) and significant increase in plasma total antioxidant capacity (TAC) concentrations (+6.4 ± 65.2 vs. ?129.9 ± 208.3 mmol/L, P < 0.001). Overall, magnesium supplementation for 12 weeks among subjects with DFU had beneficial effects on parameters of ulcer size, glucose metabolism, serum hs-CRP, and plasma TAC levels. Clinical trial registration number: http://www.irct.ir: IRCT201612225623N96     

Oxidized Low Density Lipoprotein and Inflammation in Gout Patients

To analyze the levels of oxidized low density lipoprotein (ox-LDL) and inflammatory cytokines in the plasma of gout patients. The levels of ox-LDL, hypersensitive C-reactive protein (hs-CRP), interleukin-1β, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured in the plasma of 41 gout patients [28 in acute phase episode, 13 in intermittent phase (IP)], and in 40 healthy controls. The relationship between ox-LDL and inflammation was also explored by measuring the levels of several pro-inflammatory cytokines in the plasma. The plasma levels of ox-LDL, hs-CRP, IL-6 and TNF-α were significantly increased in patients with gout in the acute phase compared to those in the IP group and healthy controls (P < 0.05), but the levels of TGF-β were significantly lower in the acute phase group than in the IP group and healthy controls (P < 0.01). The levels of ox-LDL in the gout patients in the IP were significantly higher than those in healthy controls (P < 0.05). Correlation analysis indicated that the levels of ox-LDL were positively correlated with hs-CRP, IL-6 and TNF-α (r = 0.343, r = 0.386, r = 0.659, P < 0.01, respectively), but negatively correlated with TGF-β levels in patients in the acute phase (r = ?0.240, P < 0.05). The levels of ox-LDL in gout patients were significantly higher than those in healthy controls. The changes in ox-LDL levels may be associated with enhanced inflammation in gout patients.     

尼可地尔联合冠状动脉心脏介入治疗冠心病合并肾功能不全的疗效及对NGAL、Cys-C的影响

摘要 目的：探析冠心病（CHD）合并肾功能不全（RI）应用冠状动脉心脏介入治疗（PCI）联合尼可地尔的临床疗效及对胱抑素C（Cys-C）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）影响。方法：选择本院2019年6月~2021年6月就诊的86例CHD合并RI患者,随机数字表法分为两组各43例。 两组均实施PCI治疗,对照组实施常规静脉水化处理,观察组联合尼可地尔治疗。对比两组PCI治疗前后24 h肾功能指标（Cys-C、NGAL）、血清炎性因子指标（高敏C反应蛋白 (hs-CRP)、白细胞介素 6 (IL-6)）、心肌损伤指标（心肌肌钙蛋白I（cTnI）及肌酸激酶同工酶（CK-MB））、并发症发生率。结果：观察组CIN发生率（2.33%）、MACE率（2.33%）均明显低于对照组（16.28%、13.95%）,有统计学差异（P<0.05）。两组PCI治疗前Cys-C、NGAL、hs-CRP、IL-6、cTnI、CK- MB无统计学差异（P<0.05）。治疗后观察组Cys-C、NGAL、hs-CRP、IL-6升高幅度、组cTnI、CK- MB明显低于对照组（P<0.05）。结论：PCI 联合尼可地尔应用于CHD合并RI临床治疗效果显著,可有效改善患者肾功能,降低炎症反应、心肌损伤,预防CIN发生。     

Comparison of the effects of ketamine-dexmedetomidine and sevoflurane-sufentanil anesthesia on cardiac biomarkers after cardiac surgery: an observational study

Inhalational anesthetics have demonstrated cardioprotective effects against myocardial ischemia-reperfusion injury. Clinical studies in cardiac surgery have supported these findings, although not with the consistency demonstrated in experimental studies. Recent investigations have questioned the advantages of inhalational over intravenous anesthetics with respect to cardiac protection. Ketamine has been shown to be comparable with sufentanil, and has even demonstrated anti-inflammatory properties. Dexmedetomidine has been established as a sedative/anesthetic drug with analgesic properties, and has also demonstrated myocardial protective effects. In this retrospective observational study, the influence of ketamine-dexmedetomidine-based anesthesia (KET-DEX group; n=17) on the release of cardiac biomarkers was compared with that of sevoflurane-sufentanil-based anesthesia (SEVO group; n=21) in patients undergoing elective coronary artery bypass grafting. Compared with the SEVO group, the KET-DEX group exhibited significantly reduced cardiac troponin I (2.22+/-1.73 vs. 3.63+/-2.37 microg/l; P=0.02) and myocardial fraction of creatine kinase (CK-MB) levels (12.4+/-10.4 vs. 20.3+/-11.2 microg/l; P=0.01) on the morning of the first postoperative day. Furthermore, cardiac troponin I release, evaluated as the area under the curve, was significantly reduced in the KET-DEX group (32.1+/-20.1 vs. 50.6+/-23.2; P=0.01). These results demonstrate the cardioprotective effects of ketamine-dexmedetomidine anesthesia compared with those of sevoflurane-sufentanil anesthesia.     

Urocortin-2 suppression of p38-MAPK signaling as an additional mechanism for ischemic cardioprotection

Urocortin-2 (UCN2) is cardioprotective in ischemia/reperfusion injury (I/R) through short-lived activation of ERK1/2. Key factors involved in I/R, e.g. apoptosis, mitochondrial damage, p38 kinase, and Bcl-2 family, have not been well-investigated in UCN2-induced cardioprotection. We assessed the role of p38-MAPK in anti-apoptotic Bcl-2 signaling and mitochondrial stabilization as a putative mechanisms in UCN2-induced cardioprotection. Isolated hearts from adult Sprague–Dawley rats and cultured H9c2 cells were subjected to I/R protocols with or without 10 nM UCN2 treatment. The effect of a specific p38 inhibitor SB202190 was tested in H9c2 cells. Cardiac function, LDH release, and mitochondrial membrane potential (MMP) were used to assess the degree of myocardial injury in hearts and H9c2 cells. Post-perfusion, hearts were collected for Western blot analyses or mitochondria/cytosol isolation to analyze p38 activation and Bcl-2 family members. UCN2 treatment improved rate-pressure product (58 ± 5 vs. 31 ± 4 % of Baseline; P < 0.05) and decreased LDH release (20 ± 9 vs. 90 ± 40 mU/ml LDH, P < 0.01) at the end of 60 min reperfusion. UCN2 reduced phospho-p38 levels and Bax activation. UCN2 increased the expression of Bcl-2 and inhibited the accumulation of p-Bim. With additional experiments, it was confirmed that UCN2 increases the phosphorylation of ERK1/2 in the early phase of UCN2 treatment and increases the overshot recovery of ERK1/2 phosphorylation during reperfusion. UCN2 and SB202190 partially prevented the loss of MMP induced by I/R. However, combined treatment with UCN2 and SB202190 did not provide additive benefit. UCN2 is cardioprotective in I/R in association with reduced phosphorylation of p38 together with the increased ERK1/2 activation and increased Bcl-2 family member pro-survival signaling. These changes may stabilize cardiac mitochondria, similar to p38 inhibitors, as part of a pro-survival mechanism during I/R.     

Genetic Variants in C-Reactive Protein and Ischemic Stroke Susceptibility

Considerable discrepancies in the previously reported associations of the C-reactive protein (CRP) gene variants and ischemic stroke (IS) risk prompted us to perform this meta-analysis. We selected the fixed effects Mantel–Haenszel method to estimate the risk of IS [OR (odds ratio) along with its 95 % CI (confidence interval)] in relation to the CRP variants (?717 A > G, 1444 C > T). Heterogeneity test, influence analysis and publication bias test were appropriately performed using respective methods. We analyzed 1,926 IS patients and 2,678 controls and found the ?717 A > G variant was not significantly associated with overall IS risk. Subsequent analysis of the 1444 C > T variant involving 3,278 samples similarly revealed no significant association with IS. There was no substantial heterogeneity or publication bias in this analysis. Our meta-analysis may provide first evidence showing that genetic variants within the CRP locus are unlikely to modulate risk of IS.     

Mannose-Binding Lectin (MBL) and MBL-associated serine protease-2 (MASP-2) in women with malignant and benign ovarian tumours

Mannose-Binding Lectin (MBL) is a serum pattern recognition molecule, able to activate complement in association with MASP proteases. Serum levels of MBL and MASP-2, activities of MBL–MASP complexes, single nucleotide polymorphisms of the MBL2 and MASP2 genes and/or their specific mRNA expression in ovarian sections were investigated in 128 patients suffering from primary ovarian cancer (OC) and compared with 197 controls (C), encompassing both patients with benign ovarian tumours (n = 123) and others with no ovarian pathology (n = 74). MBL deficiency-associated genotypes were more common among OC patients than among controls. The O/O group of genotypes was associated with ovarian cancer (OR 3.5, p = 0.02). In A/A homozygotes, MBL concentrations and activities were elevated in the OC group and correlated with C-reactive protein. Moreover, high MBL serum levels were associated with more advanced disease stage. No differences in distribution of the MASP2 +359 A>G (D120G) SNP or MASP-2 serum levels were found between cancer patients and their controls. However, the highest frequency of the A/G (MASP2) and LXA/O or O/O (MBL2) genotypes was found among OC patients with tumours of G1–2 grade (well/moderately differentiated). Furthermore, MBL deficiency-associated genotypes predicted prolonged survival. None of the parameters investigated correlated with CA125 antigen or patients’ age. The local expression of MBL2 and MASP2 genes was higher in women with ovarian cancer compared with controls. It is concluded that the expression of MBL and MASP-2 is altered in ovarian cancer, possibly indicating involvement of the lectin pathway of complement activation in the disease.     

A polymorphism in the visfatin gene promoter is related to decreased plasma levels of inflammatory markers in patients with coronary artery disease

Visfatin, a newly identified proinflammatory adipokine, has been linked to coronary artery disease (CAD). The ?1535C>T polymorphism (rs61330082) located in the visfatin gene promoter is reportedly associated with proinflammatory status. However, it is unclear whether this polymorphism correlates with plasma levels of inflammatory markers including visfatin, hs-CRP, IL-6 and TNF-?? in CAD patients. The present study was to investigate the potential association of the ?1535C>T polymorphism with plasma levels of visfatin, IL-6, C reactive protein (hs-CRP) and TNF-?? in patients with CAD. We conducted a hospital based study with 171 CAD patients to examine the association between the ?1535C>T polymorphism and plasma levels of visfatin, hs-CRP, IL-6 and TNF-??. Plasma visfatin levels were markedly different between patients with stable angina pectoris (SAP, 11.91 ± 0.70 ng/l) and those with unstable angina pectoris (UAP, 17.49 ± 0.20 ng/l) or acute myocardial infarction (AMI, 16.63 ± 0.22 ng/l; SAP versus UAP or AMI, P < 0.05). Compared with the CC genotype, variant genotypes CT and TT correlated with significantly lower levels of visfatin, hs-CRP, IL-6 and TNF-?? in the SAP group (P < 0.05), with lower levels of hs-CRP and IL-6 in the UAP group (P < 0.05), and with lower levels of visfatin in the AMI group (P < 0.05) after adjustment for age, gender, smoking, hypertension, diabetes, dyslipidemia and medication. Our results suggest that the ?1535C>T polymorphism is associated with decreased plasma levels of inflammatory markers in CAD patients, reflecting that this polymorphism might provide a useful marker for predicting the development of CAD events.