Angiographically evident thrombus following fibrinolytic therapy is associated with impaired myocardial perfusion in STEMI: a CLARITY-TIMI 28 substudy.

AIMS: The presence of residual thrombus following fibrinolytic therapy for ST-segment elevation myocardial infarction (STEMI) may predispose to greater embolization and microvascular dysfunction. METHODS AND RESULTS: We hypothesized that even in the presence of a patent epicardial artery, residual thrombus would be associated with worsened TIMI myocardial perfusion grades (TMPG), independent of epicardial flow. Data were analysed from the angiograms of 2684 patients enrolled in the CLARITY-TIMI 28 trial, with angiographically patent arteries (TIMI 2/3 flow) at a median of 88 h following fibrinolytic therapy. Thrombus in a patent epicardial artery was observed more frequently among patients with shorter times from randomization to angiography, among patients with non-left anterior descending infarctions, and among patients treated with placebo (vs. clopidogrel). Thrombus was associated with more frequent TIMI 2 flow (35.1 vs. 22.1%, P < 0.001), higher corrected TIMI frame counts (CTFC) (42 vs. 33 frames, P < 0.001), and a lower incidence of normal TMPG 3 (48.7 vs. 63.9%, P < 0.001), irrespective of treatment with clopidogrel or placebo. In multivariable analyses, thrombus remained associated with higher CTFC (P < 0.001) and worse TMPG (OR 1.6 for TMPG 0/1/2, P < 0.001) after adjustment for baseline covariates as well as known correlates of TMPG. The association between thrombus and impaired TMPG remained even after further adjustment for CTFC or TIMI flow grade. CONCLUSION: Residual angiographic thrombus following fibrinolytic therapy in STEMI patients is associated with impaired myocardial perfusion, independent of epicardial flow. This finding emphasizes the roles of platelet aggregation and distal embolization in the pathogenesis of microvascular dysfunction in STEMI.     

Survivin在子宫内膜样腺癌中的表达

目的研究Survivin在正常子宫内膜、子宫内膜不典型增生和子宫内膜样腺癌(EA)三种组织中表达的差异。方法选取华北石油管理局总医院2010年1月~2012年6月手术切除子宫并经病理证实的EA存档标本40例(EA组),经诊刮或宫腔镜检查病理结果示子宫内膜不典型增生20例(AHE组),同时选取同期因子宫脱垂或子宫肌瘤行子宫切除的正常子宫内膜20例作为对照(CON组)。通过免疫组织化学法检测三组中Survivin表达情况的差异。应用SPSS 16.0统计软件进行数据分析。结果 EA组的Survivin表达阳性率为90%,显著高于CON组(75%),差异有统计学意义(P<0.05)。在EA组中,组织分级为G1、G2、G3级的患者Survivin阳性率分别为85.0%、90.9%、100.0%,差异有统计学意义(P<0.05);手术-病理分期为Ⅰ期、Ⅱ期、Ⅲ期的患者Survivin阳性率分别为62.1%、85.7%、100.0%,差异有统计学意义(P<0.05);肌层浸润深度<1/2及≥1/2的患者Survivin阳性率分别为88.5%、92.9%,差异无统计学意义(P>0.05);存在淋巴结转移及无淋巴结转移的患者Survivin阳性率为100.0%、80.6%,差异无统计学意义(P>0.05);存在脉管浸润及无脉管浸润的患者Survivin阳性率分别为100.0%、84.2%,差异无统计学意义(P>0.05)。结论相较于正常子宫内膜,EA组织中Survivin表达显著增多。Survivin的阳性表达率与EA组织学分级和手术-病理分期相关,与肌层浸润、淋巴结转移及有无脉管浸润无关。     

A-kinase interacting protein 1 is sufficiently expressed and positively associates with WHO grade,meanwhile predicts unfavorable overall survival independently in glioma patients

The present study aimed to investigate the association of A-kinase interacting protein 1 (AKIP1) with clinical characteristics, and further explore the prognostic value of AKIP1 in glioma patients.Totally 168 glioma patients who underwent tumor resection were analyzed, and their tumor tissue specimens were acquired for the detection of AKIP1 expression by immunohistochemistry (IHC), which was scored by a semi-quantitative method considering staining intensity and staining density.According to AKIP1 expression in tumor tissues of glioma patients, there were 65 (38.7%) patients with AKIP1 low expression (IHC score 0–3), 48 (28.6%) patients with AKIP1 high + expression (IHC score 4–6), 42 (25.0%) patients with AKIP1 high++ expression (IHC score 7–9) and 13 (7.7%) patients with AKIP1 high+++ expression (IHC score 10–12), respectively. AKIP1 expression was positively associated with World Health Organization grade. Overall survival (OS) was the lowest in the patients with AKIP1 high+++ expression, followed by those with AKIP1 high++ expression and those with AKIP1 high+ expression, and highest in those with AKIP1 low expression. Further subgroup analysis exhibited that AKIP1 expression was negatively associated with OS especially in high-grade glioma patients. In addition, AKIP1 expression was negatively associated with OS in all subgroups of patients with/without adjuvant radiotherapy, with/without adjuvant chemotherapy. Further multivariate Cox''s regression exhibited that AKIP1 high expression was an independent predictive factor for worse OS.AKIP1 presents with the potential to be a novel biomarker for tumor management and prognosis surveillance in glioma patients.     

Do we over treat mild hypertension?

The important question whether ‘mild’ hypertension should or should not be treated by drugs is difficult to answer, because the only randomized controlled trials (RCTs) investigating this question were conducted when the definition of ‘mild’ hypertension was based on diastolic blood pressure only, whereas the present definition of grade 1 hypertension includes both systolic and diastolic values (SBP/DBP), and the concept of ‘mild’ hypertension also includes that of low-moderate cardiovascular risk (< 5% cardiovascular death rate in 5 years). Due to the lack of evidence from specific RCTs, guidelines recommend drug treatment of mild hypertension only on the basis of expert opinion. However, recent meta-analyses have provided some support to drug treatment intervention in low-moderate risk grade 1 hypertensives and have shown that, when treatment is deferred until organ damage or cardiovascular disease occur, absolute residual risk (events occurring despite treatment) markedly increases. Although evidence favoring therapeutic intervention in mild hypertension is nowadays stronger than expert opinion, meta-analyses are not substitutes for specific RCTs, and the wide BP spans defining grade 1 hypertension as well as the span defining low-moderate risk leave a wide space for individualized or personalized decisions.     

COL5A2 as a potential clinical biomarker for gastric cancer and renal metastasis

Background:Gastric cancer, characterized by insidious onset and multiple metastasis, is almost incurable and has poor prognosis, and also one of the leading causes of treatment failure and death in patients with gastric cancer (GC). However, the prognosis of collagen type V alpha2 chain (COL5A2) in GC and renal metastasis is unknown.Methods:Recruited 148 patients who underwent GC. The diagnosis of GC was confirmed by ultrasound imaging and pathological examination. Immunohistochemistry and RT-qPCR were performed to exam the expression level of COL5A2. The statistical methods included Pearson chi-square test, Spearman-rho correlation test, univariate and multivariate cox regression analysis. Finally, this research constructed receiver operating characteristic (ROC) curves and applied the area under the curve (AUC).Results:Based on Pearson''s chi-square test, Spearman-rho test, and univariate/multivariate cox regression, pathologic grade (P < .001), renal metastasis (P < .001) and staging (P < .001) were significantly related to COL5A2. And COL5A2 expression (hazard ratio [HR]: 18.834, P < .001) is an independent risk factor of GC. The AUC was used as the degree of confidence in judging each factor: COL5A2 (AUC = 0.878, P < .001), COL1A1 (AUC = 0.636, P = .006), COL1A2 (AUC = 0.545, P = .368), and COL3A1 (AUC = 0.617, P = .019). Through the ROC result, COL5A2 had more advantage as a biomarker for GC than other collagens.Conclusions:COL5A2 gene expression level might be a risk factor for GC. COL5A2 has a strong correlation with the prognosis of the disease.     

Generation of clinical‐grade functional cardiomyocytes from human embryonic stem cells in chemically defined conditions

A highly efficient cardiac differentiation from human pluripotent stem cells (hPSCs) is achievable using existing methods, especially with the standard B27 induction system. However, bovine serum albumin (BSA), one of the essential ingredients in B27, may pose significant complications for clinical studies owing to its animal origin and potential risks of virus contamination. Furthermore, the high cost of the B27 induction system also limits the applications of hPSCs‐derived cardiomyocytes. Here, a BSA‐free and chemically defined medium has been developed for differentiating hPSCs to clinical‐grade cardiomyocytes, which generated over 80% cardiac troponin T (cTNT)‐positive cardiomyocytes with high yield. When engrafting the cardiomyocytes into the hearts of myocardial infarction model rats, the rats survived with significantly improved heart functions in Δ ejection fraction and Δ fractional shortening. Importantly, the human embryonic stem cell (hESC) line (Q‐CTS‐hESC‐2) chosen for differentiation was of a clinical‐grade maintained in defined xeno‐free conditions. Compliant with the biological safety requirements, the Q‐CTS‐hESC‐2‐derived cardiomyocytes have passed the sterility and pathogen criteria tests for clinical applications. This study reports, for the first time, the generation of clinical‐grade and functional cardiomyocytes from hPSCs where BSA‐free and chemically defined conditions were maintained throughout the whole process. This provides the possibility of future therapeutic use of clinical‐grade hPSCs‐derived cardiomyocytes in treating heart diseases. Copyright © 2016 John Wiley & Sons, Ltd.     

颅脑损伤患者血清NF-L、TSP-1水平变化及临床意义

目的 探讨颅脑损伤患者血清神经丝蛋白轻链(NF-L)、血小板反应蛋白1(TSP-1)水平变化,分析其对颅脑损伤患者预后的预测价值。方法 选择106例颅脑损伤患者(颅脑损伤组),根据Fisher CT分级将患者分为1～2级组(47例)和3～4级组(59例),根据格拉斯哥昏迷评分(GCS)将患者分为轻型昏迷组(12～15分,34例)、中型昏迷组(7～11分,49例)和重型昏迷组(＜7分,23例),根据伤后30天格拉斯哥预后量表(GOS)将患者分为预后不良组(GOS评分1～3分,48例)和预后良好组(GOS评分4～5分,58例),另选择门诊体检部接诊的103例健康志愿者(对照组)。采用酶链免疫吸附试验检测血清NF-L、TSP-1水平。Spearman秩相关分析颅脑损伤患者血清NF-L、TSP-1水平与Fisher CT分级、GCS评分、GOS评分之间的相关性。Logistic回归分析影响颅脑损伤患者预后的危险因素,受试者工作特征(ROC)曲线分析血清NF-L、TSP-1水平预测颅脑损伤患者预后的价值。结果 颅脑损伤组血清NF-L、TSP-1水平均高于对照组(P＜0.05),Fisher CT分级3～4级组血清NF-L、TSP-1水平高于1～2级组(P＜0.05),重型昏迷组血清NF-L、TSP-1水平高于中型昏迷组和轻型昏迷组(P＜0.05),中型昏迷组血清NF-L、TSP-1水平高于轻型昏迷组(P＜0.05),预后不良组血清NF-L、TSP-1水平高于预后良好组(P＜0.05)。Spearman秩相关分析表明血清NF-L、TSP-1水平与Fisher CT分级呈正相关(r_s=0.622、0.593,P＜0.05),与GCS评分、GOS评分呈负相关(r_s=－0.589、－0.693;－0.629、－0.617,P＜0.05)。Logistic回归分析结果显示Fisher CT分级、GCS评分、NF-L、TSP-1与颅脑损伤患者预后相关(P＜0.01)。ROC曲线分析显示血清NF-L、TSP-1水平预测颅脑损伤患者预后的曲线下面积(AUC)分别为0.823、0.836,联合NF-L、TSP-1预测颅脑损伤患者预后的AUC为0.937,高于单独NF-L、TSP-1(P＜0.05)。结论 颅脑损伤患者血清NF-L、TSP-1水平显著升高,NF-L、TSP-1水平与颅脑损伤严重程度和预后密切相关,可作为预后评估的参考指标。     

胃间质瘤内镜超声征象与病理危险分级的相关性研究

探讨胃间质瘤不同内镜超声征象与其危险分级间的相关性。回顾性分析2013年3月—2017年12月在武汉大学中南医院内镜中心行普通胃镜及内镜超声检查,经病理和免疫组化确诊为胃间质瘤的89例患者资料,比较不同危险程度胃间质瘤内镜超声下特征。89例患者中,极低危险度63例、低危险度21例、中危险度5例,内镜超声下胃间质瘤直径、回声均匀性、溃疡、边界是否规则及囊性变在不同危险度胃间质瘤中差异有统计学意义（P＜0.05）。内镜超声检查有助于不同危险度胃间质瘤的判断。     

非活动性HBsAg携带者临床病理分析

目的 了解非活动性HBsAg携带者临床病理特点.方法 对80例患者进行生化、病毒标志物及病毒定量检测,并和肝脏病理进行相关性分析.结果 光镜下见肝组织基本正常者1例,病理诊断为慢性肝炎轻度者48例,中度以上者19例,占23.75%,活动性肝硬化者12例,占15%;抗Hbe阴性组纤维化程度要重于抗Hbe阳性组,其中大于S3的抗Hbe阴性组患者占总数的60%,阳性组为26%,但肝脏炎症程度与抗Hbe水平无关;血小板和胆碱酯酶对于代偿期肝硬化的诊断具有辅助价值.结论 对于非活动性HBsAg携带者应尽可能进行肝脏病理检查以明确诊断,并指导治疗.