Pathological classification and prognosis of renal damage caused by antineutrophil cytoplasmic antibody associated vasculitis

Objective To analyze the pathological characteristics and prognostic factors of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods A retrospective analysis of AAV patients with renal biopsy results admitted to Kidney Disease Center of the First Affiliated Hospital from January 2004 to February 2017 was performed. The patients were divided into 4 types according to Berden classification, and their clinical, pathological characteristics and prognosis were compared. The survival curves of each type of patients were plotted by Kaplan-Meier method, and the difference of survival curves was compared using Log-rank test. With entering the maintenance dialysis as the endpoint, Cox regression was used to analyze the prognostic factors. Results A total of 175 patients with AAV, including 59 cases (33.7%) of focal type, 39 cases (22.3%) of crescent type, 32 cases (18.3%) of sclerosis type, 45 cases (25.7%) of mixed type. The basal serum creatinine levels in crescent type group and sclerosis type group were significantly higher than those in the focal type group or mixed type group (all P＜0.05), and loop necrosis rate in sclerosis type group was significantly lower than chat in the focal type group or crescent type group (both P＜0.05). The median follow-up period was 11.8 (0.5-86.7) months. The event-free survival rates were 83.1%, 77.8%, 64.1% and 50.0% in the focal type, mixed type, crescent type and sclerotic type groups (Log-rank χ2=11.537, P=0.009). Cox regression analysis showed higher parathyroid hormone (HR=1.013, 95%CI 1.007-1.019, P＜0.001), glomerular sclerosis ≥50% (HR=10.532, 95%CI 2.903-38.203, P＜0.001) were independent risk factors for AAV patients entering maintenance dialysis, and higher estimated glomerular filtration rate (HR=0.943, 95%CI 0.896-0.993, P=0.025) was protective factor. Conclusion The prognosis of AAV renal damage is worsened according to focal, mixed, crescent and sclerosis types. Lower estimated glomerular filtration rate, higher parathyroid hormone and glomerular sclerosis ≥50% are independent risk factors for AAV patients entering maintenance dialysis.     

Bypass Surgery or Stenting for Left Main Coronary Artery Disease in Patients With Diabetes

Background

The randomized EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial reported a similar rate of the 3-year composite primary endpoint of death, myocardial infarction (MI), or stroke in patients with left main coronary artery disease (LMCAD) and site-assessed low or intermediate SYNTAX scores treated with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). Whether these results are consistent in high-risk patients with diabetes, who have fared relatively better with CABG in most prior trials, is unknown.

基于RhoA/ROCK-1通路研究针刺干预SHR脑保护作用机制

[目的]明确自发性高血压大鼠(SHR)脑损害与RhoA、ROCK-1的相关性,探讨针刺干预SHR脑保护的Rho通路机制。[方法]将SHR随机分为模型对照组、太冲穴组,WKY大鼠设为正常对照组。太冲穴组针刺干预4周,其余两组在干预期内给予相同程度、相同时长的抓取。观测各组大鼠收缩压、舒张压、平均动脉压的改变;苏木精-伊红(HE)染色观察脑组织形态学改变;蛋白免疫印迹(Western blot)法测定各组大鼠脑组织中RhoA、ROCK-1的表达水平。[结果]在干预周期内,正常对照组收缩压、舒张压、平均压均处于正常血压范围内。与正常对照组比较,模型对照组收缩压、舒张压、平均压均较高,且有随着周龄增加而增高的趋势。与模型对照组相比,太冲穴组可有效降低收缩压,有降低舒张压、平均压的趋势。模型对照组较正常对照组脑组织细胞排列紊乱,细胞坏死及间质水肿程度加重,RhoA、ROCK-1表达升高;太冲穴组与模型对照组比较,脑细胞排列规则,细胞坏死及间质水肿消失,RhoA、ROCK-1表达下降。[结论]针刺太冲穴能有效降低SHR血压,改善脑损害,其机制可能与抑制RhoA/ROCK-1信号通路表达相关。     

急性心肌梗死后左心室游离壁破裂患者临床特点分析

目的探讨急性心肌梗死(acute myocardial infarction,AMI)后发生左心室游离壁破裂(free wall rupture,FWR)患者的临床特点及危险因素。方法入选2010年12月至2018年12月南京医科大学附属南京医院明确诊断为AMI的患者4221例,其中发生FWR的患者81例(FWR组),按照1:5匹配原则,随机选取未发生心脏破裂(且未发生室间隔穿孔)的患者405例作为非FWR组,比较两组患者临床基线资料及预后。结果(1)AMI患者中出现FWR的风险为1.9%。(2)与非FWR组相比,FWR组患者年龄偏大,前壁心肌梗死较多,心功能更差,接受手术治疗(包括经皮支架植入和冠状动脉旁路移植术)的患者比例偏低,且所有患者均出现院内死亡。(3)91.4%的患者FWR发生在AMI起病1周之内,其中24 h内发生FWR 37例(45.7%)。(4)COX回归分析发现,年龄(HR=1.055,95%CI:1.032~1.078,P<0.001)、急性前壁心肌梗死(HR=1.907,95%CI:1.211~3.002,P=0.005)和手术治疗(HR=0.126,95%CI:0.072~0.220,P<0.001)是AMI患者出现FWR的独立预测因子。结论AMI患者发生FWR的风险约为1.9%,而且通常发生在心肌梗死1周内,高龄和急性前壁心肌梗死患者容易发生FWR,而手术治疗能明显降低FWR风险。     

Cardioprotective effect of hemin in isoprenaline-induced myocardial infarction: role of ATP-sensitive potassium channel and endothelial nitric oxide synthase

Ischemic heart disease is a common cardiac health problem. Despite the significant advances in prevention and treatment of this disorder, its incidences and complications are very serious. So, the search for more antioxidants and anti-inflammatory agents with cardioprotective effects is an urgent task. We aimed to evaluate the effects of a heme oxygenase 1 (HO1) inducer, hemin (HEM), on isoprenaline (ISO)-induced myocardial damage. Forty-five Wistar albino rats were used. Animals were treated with HEM (25 mg/kg/day) i.p. for 5 days and injected with ISO (150 mg/kg/day) i.p. on 4th and 5th day of the experiment. Detection of the role of ATP-sensitive potassium channel (K_ATP) was performed by administration of glibenclamide (GP) (5 mg/kg/day) orally 2 h before HEM. Moreover, the role of endothelial nitric oxide synthase (eNOS) was detected by coadministration of Nitro- ω-L-arginine (L-NNA) (25 mg/kg/day) for 5 days. The ISO group showed increase in heart weight, cardiac enzymes, tumor necrosis factor alpha (TNFα), and malondialdehyde (MDA) with decrease in reduced glutathione (GSH), HO1, and total antioxidant capacity (TAC). In addition, there were increases in Bcl-2 associated X protein (Bax) and cleaved caspase-3, but decreases in B-cell lymphoma-2 (Bcl-2) and eNOS. Moreover, the histopathological examination of the ISO group showed degeneration of the cardiac muscle fibers and marked infiltration of the inflammatory cells. The biochemical and histopathological changes induced by ISO were markedly ameliorated in the HEM plus ISO group. This protective effect was diminished with coadministration of GP or L-NNA; thus, K_ATP and eNOS might mediate HEM cardioprotection.     

活心方对急性心肌梗死大鼠血流动力学及梗死面积的影响

目的观察活心方对结扎冠状动脉前降支所致急性心梗大鼠血流动力学及梗死面积的影响。方法采用结扎冠状动脉前降支的方法构建急性心梗模型,大鼠随机分为假手术组、模型组、贝复济组、血竭小复方组和活心方组,干预8周。检测大鼠血流动力学指标,HE染色观察心肌组织形态改变,计算梗死面积。结果模型组大鼠心肌梗死面积与左室收缩压(LVSP)及左室内压最大变化速率(+LVdp/dtmax)呈负相关(P=0.001),与左室舒张末期压(LV-EDP)呈正相关(P=0.005)。与模型组比较,活心方组、血竭小复方组大鼠LVSP均升高(P<0.05,P<0.01),LV-EDP降低(P<0.01),+LVdp/dtmax加大(P<0.01),-LVdp/dtmax加大(P<0.05,P<0.01),梗死面积缩小(P<0.01);与血竭小复方组比较,活心方组大鼠LVSP增高(P<0.05)、+LVdp/dtmax加大(P<0.05);梗死面积更小(P<0.05)。结论心肌梗死大鼠梗死面积与血流动力学指标存在相关性。活心方干预能缩小心梗大鼠的梗死面积,改善心梗后大鼠左室舒缩功能,并优于血竭小复方。     

The third-generation retinoid adapalene triggered DNA damage to induce S-phase arrest in HaCat cells

Epidermal proliferative diseases consisted of a series of common skin diseases, most of which were recurrent chronic skin diseases, and had greatly negative influence on the life quality of patient. Retinoids exhibited vital roles in the treatment of many skin diseases. Our recent study demonstrated that adapalene significantly inhibited the growth of HaCat cells, and the inhibitory activity was stronger than other retinoids, such as all-trans-retinoic acid, acitretin, isotretinoin, tazarotene, and bexarotene. Further study showed that adapalene suppressed the colony formation of HaCat cells, and it dramatically triggered S-phase arrest and apoptosis, rather than G1 phase arrest which was reported in other retinoids in several studies. Additionally, adapalene treatment greatly upregulated the protein expression of DNA damage marker γ-H2AX, which was in accord with the results of the elongation of tail moment by comet electrophoresis analysis. Moreover, DNA damage was triggered and DNA repair was suppressed synchronously with adapalene treatment, which accounted for the mechanism of S-phase arrest induced by adapalene. In summary, our recent work demonstrated that adapalene showed strong anti-proliferation activity in HaCat cells and could be an alternative agent for the epidermal proliferative disease.     

Arterial Lactate in Cardiogenic Shock: Prognostic Value of Clearance Versus Single Values

ObjectivesThis study sought to compare single lactate values at admission (L1) and after 8 h (L2) with lactate clearance (LC) for mortality prediction in cardiogenic shock (CS).BackgroundEarly estimation of prognosis in CS complicating acute myocardial infarction is crucial for tailored treatment selection. Arterial lactate is the most widely used point-of-care parameter in CS. In septic shock, lactate reduction over time—LC—has been extensively investigated. However, in CS, only limited data exist, and the prognostic value of LC is unknown.MethodsThis study is a subanalysis of the IABP-SHOCK II (Intraaortic Balloon Pump in Cardiogenic Shock II) trial and the corresponding registry. Lactate levels were prospectively collected. All-cause mortality at 30 days was assessed as primary endpoint.ResultsFor 671 of 783 (85.7%) patients, L1 and L2 values were available. The area under the receiver-operating characteristic curve (L1: 0.69; L2: 0.76; LC: 0.59) showed no difference between L1 and LC (p = 0.20). In contrast, L2 was a significantly better predictive parameter than L1 or LC (p < 0.001 for both). In multivariable stepwise Cox regression analysis, L2 ≥3.1 mmol/l (best cutoff value by Youden index) and LC <–3.45%/h remained independently predictive for time to death (p < 0.001 for both), with L2 showing the highest chi-square test score (42.1) and hazard ratio (2.89; 95% confidence interval: 2.10 to 3.97).ConclusionsArterial lactate after 8 h is superior in mortality prediction in comparison with baseline lactate and LC. A cutoff value of 3.1 mmol/l for lactate after 8 h showed the best discrimination for assessing early prognosis in CS and may serve as new treatment goal. (Intraaortic Balloon Pump in Cardiogenic Shock II [IABP-SHOCK II]; NCT00491036)