不同缺血时间再灌注损伤对大鼠骨骼肌的影响

目的探讨不同缺血时间再灌注损伤对大鼠骨骼肌的影响。方法选取35只雄性Wistar大鼠,采用单侧夹闭股动脉和压力绷带施压的方法构建下肢骨骼肌缺血再灌注损伤(IRI)模型。根据不同缺血时间分为2 h缺血24 h再灌注(I2R24组)、2.5 h缺血24 h再灌注(I2.5R24组)、3 h缺血24 h再灌注(I3R24组)、4 h缺血24 h再灌注(I4R24组)、假手术组,每组7只。在再灌注终点,收集腓肠肌组织和血浆进行分析。采用湿重/干重比值(W/D)评估组织水肿情况;3-(4,5-二甲基噻唑-2)-2,5二苯基四氮唑溴盐(MTT)检测组织活力;HE染色观察组织病理学变化;免疫荧光染色检测补体C1q和C3b/c沉积、凝血组织因子(TF)表达和纤维蛋白原(FN)沉积、缓激肽受体1(BR1)和BR2表达、内皮血管细胞黏附分子-1(VCAM-1)和E选择素表达、炎症纤维介素蛋白-2(FGL-2)和髓过氧化物酶(MPO)表达;ELISA法检测血浆干扰素-γ(IFN-γ)、白细胞介素-7(IL-7)、IL-18、巨噬细胞炎症蛋白-1α(MIP-1α)、单核细胞趋化蛋白-1(MCP-1)水平。结果延长缺血时间再灌注,组织水肿逐渐加重,I2R24组、I2.5R24组、I3R24组、I4R24组W/D分别为5.3±0.2、6.1±0.3、6.9±0.2、7.6±0.3,高于假手术组的4.5±0.1(P均<0.01)。组织活力逐渐降低,I2R24组、I2.5R24组、I3R24组、I4R24组分别为(62.4±3.5)%、(45.3±3.3)%、(35.4±3.4)%、(27.1±5.9)%,低于假手术组的(93.8±7.2)%(P均<0.01)。病理组织损伤逐渐加重,最重为I4R24组,有严重肌细胞损伤、间质水肿和大量炎性细胞浸润,余依次为I3R24组、I2.5R24组、I2R24组,假手术组肌细胞结构完整、排列整齐。免疫荧光染色提示C1q、C3b/c、FN、BR1、VCAM-1、E选择素、FGL-2水平逐渐升高,由低到高依次为假手术组、I2R24组、I2.5R24组、I3R24组、I4R24组。MPO阳性细胞数/高倍镜(×200)细胞总数的大体比例逐渐升高,从高到低依次为I4R24组、I3R24组、I2.5R24组、I2R24组、假手术组。而TF和BR2表达在各组间无明显改变。血浆IFN-γ、IL-7、IL-18、MIP-1α、MCP-1浓度随缺血时间延长均逐渐升高(P均<0.01),从低到高依次为假手术组、I2R24组、I2.5R24组、I3R24组、I4R24组(P均<0.01)。结论延长缺血时间再灌注增加补体、凝血、激肽、内皮细胞激活及炎症因子释放,从而加重大鼠骨骼肌组织损伤。     

下肢动脉硬化闭塞症患者支架植入术后血清miR- 140- 5p与1年内支架内再狭窄相关性研究

【摘要】 目的 探讨下肢动脉硬化闭塞症（LEAOD）患者支架植入术后血清微小核糖核酸（miR）-140-5p表达水平与1年内支架内再狭窄（ISR）的关系。方法 选取2019年2月至2020年3月在山西白求恩医院接受支架植入术治疗的136例LEAOD患者作为研究对象。根据术后是否发生ISR分为ISR组（n=52）和非ISR组（n=84）。采用实时荧光定量聚合酶链反应（PCR）检测患者血清miR-140-5p表达,受试者工作特征曲线（ROC）评价miR-140-5p预判支架植入术后1年内ISR的价值,logistic回归分析miR-140-5p与支架植入术后1年内ISR的关系。结果 ISR组泛大西洋学会联盟（TASC）Ⅱ分型B+C型、低密度脂蛋白胆固醇（LDL-C）、C反应蛋白（CRP）比例均高于非ISR组（均P＜0.05）。ISR组手术前后miR-140-5p相对表达水平均低于非ISR组（均P＜0.05）。两组术后miR-140-5p相对表达水平均高于术前（均P＜0.05）,ISR组miR-140-5p相对表达升高程度低于非ISR组（P＜0.05）。术后miR-140-5p预判支架植入术后1年内ISR的ROC曲线下面积（AUC）高于术前miR-140-5p、miR-140-5p差值（均P＜0.05）。logistic回归分析结果显示,TASCⅡ分型、LDL-C、CRP均为LEAOD患者支架植入术后1年内ISR的独立危险因素（均P＜0.05）,术后miR-140-5p是术后1年内ISR的独立保护因素（P＜0.05）。 结论 LEAOD患者支架植入术后miR-140-5p与术后1年内ISR相关,检测其表达可辅助临床做出更好决策。     

肝动脉化疗栓塞联合卡瑞利珠单抗治疗中晚期肝细胞癌的疗效分析

【摘要】 目的 评估肝动脉化疗栓塞（TACE）联合卡瑞利珠单抗治疗中晚期肝细胞癌（HCC）患者的疗效。方法 回顾性分析2019年6月至2021年9月106例中晚期HCC患者的临床资料。患者中接受TACE联合卡瑞利珠单抗治疗71例（联合组）,接受单药卡瑞利珠单抗治疗35例（对照组）。按1∶1比例应用倾向性得分匹配（PSM）分析2组患者疗效。主要研究终点为总生存期（OS）,次要研究终点为无进展生存期（PFS）。结果 成功匹配32对患者。PSM前,TACE联合卡瑞利珠单抗组的OS和PFS均高于单独卡瑞利珠单抗组（20.2个月比10.7个月,P=0.001;8.2个月比5.2个月,P=0.002）。PSM后,联合治疗组OS和PFS仍优于对照组（19.6个月比10.7个月,P=0.043;7.7个月比5.2个月,P=0.013）。PSM前多因素分析显示,单药卡瑞利珠单抗（P=0.006）和Child B级（P=0.027）是患者预后较差的影响因素,而PSM后的多因素分析并未发现影响患者OS的独立预后因素。此外,2组患者的治疗相关不良反应的发生率相似,差异无统计学意义（均P＞0.05）。结论 TACE联合卡瑞利珠单抗治疗中晚期肝癌比单药卡瑞利珠单抗具有更好的生存获益,并且安全可控。     

68Ga-奥曲肽PET/CT显像患者对周围人群产生的有效剂量的估算

目的 估算68Ga-奥曲肽PET/CT显像患者对周围人群产生的有效剂量。 方法 采用简单随机抽样的方法选取2021年10至12月于北京大学肿瘤医院接受68Ga-奥曲肽PET/CT显像的20例患者进行前瞻性研究,其中男性15例、女性5例,年龄30~68（49.0±12.2）岁。在患者静脉注射68Ga-奥曲肽0 h后,使用辐射监测剂量仪测量距患者1.0 m处的空气吸收剂量率,注射1.0 h后测量距患者0.3 m处的空气吸收剂量率,注射1.5 h后测量距患者0.3、0.5、1.0和1.5 m处的空气吸收剂量率。依据美国国家辐射防护和测量委员会第155号报告提出的人类社会活动模式,采用积分法估算68Ga-奥曲肽PET/CT显像患者对周围人群产生的有效剂量。 结果 注射68Ga-奥曲肽0 h后,距患者1.0 m处的空气吸收剂量率为12.97~33.67 （20.24±6.57） μSv/h;注射1.0 h后,距患者0.3 m处的空气吸收剂量率为32.73~57.69（48.98±6.20） μSv/h;注射1.5 h后,距患者0.3、0.5、1.0、1.5 m处的空气吸收剂量率分别为24.04~42.39（35.98±4.56） μSv/h、11.83~28.83（20.70±4.55） μSv/h、5.17~13.42（8.07±2.61） μSv/h、1.51~7.01（3.75±1.72） μSv/h。与68Ga-奥曲肽显像患者白天接触的家庭成员受照的有效剂量为8.22~21.33（12.83±4.15） μSv,夜间同床共睡的家庭成员受照的有效剂量为38.92~68.62（58.25±7.38） μSv,单位同事受照的有效剂量为8.37~21.73（13.06±4.23） μSv,同车邻座乘客受照的有效剂量为32.97~58.15（49.36±6.26） μSv。每接触一例患者,操作人员受照的有效剂量为2.66~4.69（3.98±0.50） μSv,陪护护士受照的有效剂量为9.70~25.17（15.13±4.90） μSv。 结论 68Ga-奥曲肽PET/CT显像患者对周围人群产生的有效剂量远低于国家标准规定的有效剂量限值。     

超声心动图对三尖瓣下移畸形术前诊断及术后疗效评价的作用

目的探讨超声心动图诊断三尖瓣下移畸形(Ebstein anomaly)的准确性和对术后近期疗效的评价。方法8例行Ebstein anomaly手术的患者,术前均经超声心动图明确诊断,同时评价三尖瓣下移的程度、瓣叶发育情况及活动度、房化右心室的大小、三尖瓣反流程度及右心室功能等指标。术后随访和比较超声心动图变化及评价手术疗效。结果8例患者均有隔叶下移,三尖瓣环扩张和前叶发育异常并活动受限,伴后叶下移5例,三尖瓣中度以上反流6例,右心室功能减低1例,房化右心室大小为37mm×18mm~54mm×34mm。术中所见与术前检查基本一致。术后3~6个月进行超声心动图随访。结果显示:5例房化右心室基本消失,三尖瓣瓣叶基本回复到正常位置,3例房化右心室较前明显缩小,6例三尖瓣反流消失,所有患者三尖瓣环均明显缩小,右心室功能均正常。结论超声心动图对Ebstein anomaly术前诊断及术后疗效的评价均具有重要的作用。     

FCRL2 expression predicts IGHV mutation status and clinical progression in chronic lymphocytic leukemia

CD38 and ZAP-70 are both useful prognostic markers for B-cell chronic lymphocytic leukemia (CLL), but are variably discordant with IGHV mutation status. A total of 5 human Fc receptor–like molecules (FCRL1-5) have tyrosine-based immunoregulatory potential and are expressed by B-lineage subpopulations. To determine their prognostic potential in CLL, FCRL expression was compared with IGHV mutation status, CD38 and ZAP-70 expression, and clinical features from 107 patients. FCRL1, FCRL2, FCRL3, and FCRL5 were found at markedly higher levels on CLL cells bearing mutated IGHV genes than on unmutated CLL cells or CD19⁺ polyclonal B lymphocytes. Univariate comparisons found that similar to CD38 and ZAP-70, FCRL expression was strongly associated with IGHV mutation status; however, only FCRL2 maintained independent predictive value by multivariate logistic analysis. Strikingly, FCRL2 demonstrated 94.4% concordance with IGHV mutation compared with 76.6% for CD38 and 80.4% for ZAP-70. Compared with other indicators, FCRL2 was also superior at predicting the time to first therapy; the median treatment-free interval was 15.5 years for patients with high FCRL2 expression compared with 3.75 years for FCRL2-low patients. Our studies indicate that FCRL2 has robust predictive value for determining IGHV gene mutation status and clinical progression and thus may further improve prognostic definition in CLL.     

Plasma levels of asymmetrical dimethylarginine and adverse cardiovascular events after percutaneous coronary intervention.

AIMS: We investigated the predictive value of plasma concentration of asymmetrical dimethylarginine (ADMA) on clinical outcome in patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: One-hundred and fifty-three consecutive patients with stable angina and undergoing PCI were prospectively enrolled for clinical follow-up. Plasma ADMA levels were determined before procedure by high performance liquid chromatography. The major adverse cardiovascular events included cardiovascular death, myocardial infarction, and repeat revascularization of target vessels. Patients were grouped into tertiles according to their plasma ADMA levels. Over a follow-up period of 16 months (median), cardiovascular events occurred in 6 patients of tertile I (<0.50microM), in 17 patients of tertile II (0.50-0.62microM), and in 28 patients of tertile III (>0.62microM), P<0.001. By multivariate analysis, tertiles of ADMA levels were independently associated with a higher risk of adverse cardiovascular events after PCI (relative risk: tertile II vs I: 3.0 [1.2-7.7], P=0.022; tertile III vs I: 5.3 [2.2-12.9], P<0.001). Moreover, plasma ADMA level in the highest tertile also appeared as a significant risk factor of subsequent death and non-fatal myocardial infarction after PCI (tertile III vs I, P=0.04). CONCLUSION: Pre-procedural plasma ADMA levels may independently predict subsequent adverse cardiovascular events in patients undergoing PCI. Measurement of plasma ADMA levels could provide a rationale for risk stratification of patients by measuring ADMA levels before intervention.     

Asymmetrical dimethylarginine: a novel risk factor for coronary artery disease

BACKGROUND: Asymmetrical dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide synthase and has been associated with systemic atherosclerosis; however, the role of ADMA in patients with coronary artery disease (CAD) has not been investigated. HYPOTHESIS: The present study was designed to determine whether the plasma ADMA level predicts the presence of CAD independently, and whether the plasma ADMA level correlates with the extent and severity of coronary atherosclerosis. METHODS: In all, 97 consecutive patients with angina and positive exercise stress test were enrolled prospectively for coronary angiography. According to the result of angiography, the subjects were divided into two groups: Group I (n = 46): patients with normal coronary artery or mild CAD (< 50% stenosis of major coronary arteries); Group 2 (n = 51): patients with significant CAD (> or = 50% stenosis of majorcoronary arteries). Plasma levels of ADMA and L-arginine were determined by high-performance liquid chromatography. In addition, we used coronary atherosclerotic score to assess the extent and severity of CAD. RESULTS: The plasma levels of ADMA in Group 2 patients were significantly higher than those in Group 1 patients (0.66 +/- 0.17 microM vs. 0.44 +/- 0.09 microM, p < 0.001); these were accompanied by significantly lower plasma L-arginine/ADMA ratio in patients with significant CAD (Group 1 vs. 2: 194.0 +/- 55.3 vs. 136.7 +/- 50.3, p < 0.001). In a multivariate stepwise logistic regression analysis, both plasma ADMA level and plasma L-arginine/ADMA ratio were identified as independent predictors for CAD. Moreover, there were significant positive and negative correlations between coronary atherosclerotic score and plasma ADMA level as well as plasma L-arginine/ADMA ratio, respectively (plasma ADMA level: r = 0.518, p < 0.001; L-arginine/ADMA ratio: r = -0.430, p < 0.001). CONCLUSIONS: Both plasma ADMA level and plasma L-arginine/ADMA ratio were useful in predicting the presence of significant CAD and correlated significantly with the extent and severity of coronary atherosclerosis. Our findings suggest that plasma ADMA level may be a novel marker of CAD.