CD150在成人乙型肝炎疫苗无应答者体外外周血单个核细胞中的表达

目的 了解信号转导淋巴细胞激活分子(SLAM)CD150在乙型肝炎(乙肝)疫苗无应答者体外外周血单个核细胞(PBMC)中的表达.方法 对2007年9月至2009年12月曾行乙肝疫苗接种、HBV标志物检测均阴性的202例患者进行标准程序再免疫,再接种后第7～12个月检测抗-HBs效价.根据抗-HBs效价判定无应答者18例(男11例,女7例);选取应答者18例(男9例,女9例)作为对照.采集无应答者与应答者静脉血18 mL,淋巴细胞分离液密度梯度离心法分离PBMC,流式细胞仪测定细胞膜表面分子CD150.采用SAS统计软件包进行t检验以及Spearman 秩相关检验.结果 乙肝疫苗免疫后,在特异性刺激剂rHBsAg作用下,PBMC中CD150的表达无应答者为(39.20±10.66)%,高于应答者的(23.73±12.41)%,差异有统计学意义(t=2.1947,P<0.05);CD3+CD4+细胞中CD150的表达无应答者为(49.64±11.94)%.亦高于应答者的(37.73±11.02)%,差异无统计学意义(t=1.7175,P>0.05).在非特异性刺激剂植物血凝素(PHA)作用下,PBMC中CD150的表达在无应答者为(39.21±7.37)%,高于应答者的(23.18±12.68)%,差异有统计学意义(t=2.2835,P<0.05).在特异性刺激剂rHBsAg作用下,CD150在PBMC及CD3+CD4+细胞中与抗体效价呈负相关(r=-0.726,P<0.05).结论 CD150可能在机体接种乙肝疫苗后的无应答者中发挥一定作用.

Abstract：

Objective To study the expression of signaling lymphocytic activation molecule (SLAM)CD150 in peripheral blood mononuclear cells(PBMCs)isolated from adult non-responders to recombined yeast gene hepatitis B vaccine.Methods A total of 202 cases were recruited.All these subjects had been immunized with recombined yeast gene hepatitis B vaccine for more than one standard scheme in two years(from Sep 2007 to Dec 2009)and remained negative for hepatitis B markers(HBsAg,anti-HBs,HBeAg,anti-HBe and anti-HBc).After recruitment,all 202 subjects received another standard scheme(0,1 and 6 month)revaccination.The blood samples were collected 7 months later after the first injection of revaccination to detect anti-HBs titer.The PBMCs were isolated from 18 adult non-responders(anti-HBs titer<10 mIU/mL)and 18 adult responders(antiHBs titer≥100 mIU/mL).CD150 expression on cell surface was analyzed by flow cytometry.SAS package was used for t test and spearman rank correlation analysis.Results After rHBsAg stimulation,the percentage of PBMCs expressed CD150 was significantly higher in non-responders (39.20%±10.66%)than responders(23.73%±12.41%)(t=2.1947,P<0.05).The same trend was also observed in rHBsAg stimulated C133+CD4+T cells,but the difference was not statistically significant(49.64%±11.94%vs 37.73%±11.02%)(t=1. 7175,P>0.05).After phytohaemagglutinin (PHA)stimulation,the percentage of CD150-positive PBMCs was also significantly higher in non-responders (39.21%±7.37%)than responders(23.18%±12.68%)(t=2.2835,P<0.05).CD150 expressions in both PBMCs and CD3+CD4+T cells were negatively correlated with anti-HBs titer after rHBsAg stimulation (r=-0.726,P<0.05).Conclusion Activation of CD150 may contribute to the non-response to hepatitis B vaccine.     

MiRNA-150与糖尿病肾病

糖尿病肾病以肾间质纤维化和肾脏硬化为病理学特点,慢性低度炎性反应、氧化应激、新生血管形成、内皮功能紊乱等在糖尿病肾病的发生和发展中起重要作用.MiRNA-150参与多种炎性反应、调节炎性反应信号通路,在肾脏纤维化中表达升高,而且可以通过微泡促进新生血管形成,进而导致肾间质纤维化,肾脏硬化;其靶基因,如细胞因子信号转导抑制蛋白1 (SOCS1)、基质细胞衍生因子-1(SDF-1)/趋化因子受体4(CXCR4)等在糖尿病肾病中起保护作用.因此,miRNA-150可能通过影响其下游信号分子的表达在糖尿病肾病的发生、发展中起重要作用.     

肺结核患者外周血单个核细胞中miRNA-150的表达及意义

目的分析外周血单个核细胞(PBMC)中miRNA-150在肺结核患者(TB)及健康人群(HD)中的表达差异,探讨miRNA-150诊断活动性肺结核的应用价值。方法选择41例TB患者为实验组(其中19例为涂阳患者,22例为凃阴患者),同时选择35例HD为对照组。采集外周抗凝血利用密度梯度离心法分离PBMC,提取总RNA,利用Taq Man探针q PCR技术检测miRNA-150在各组人群中的相对表达量,以RNU6B作为内参基因。结果 miRNA-150在TB患者外周血PBMC中表达量为(8.74±1.36),显著高于健康对照组(3.544±0.59),差异有统计学意义(P0.05);应用ROC曲线分析表明,miRNA-150诊断TB的敏感性为61%,特异性为82%。痰涂片阳性TB患者中miRNA-150表达水平显著高于痰涂片阴性患者(12.30±2.43Vs 5.66±1.12),差异有统计学意义(P0.05)。结论 miRNA-150在TB患者PBMC中表达水平升高,尤其是涂阳患者,可以作为诊断TB的分子标识。     

miR-150及其靶基因IRAK2在变应性鼻炎小鼠模型中的表达

目的探讨miR-150及其靶基因IRAK2在变应性鼻炎小鼠鼻黏膜中的表达及其作用。方法SPF级Balb/c小鼠20只,随机分为两组,变应性鼻炎模型组(AR)、对照组(NC),每组10只。模型组用卵清蛋白(OVA)致敏建立变应性鼻炎小鼠模型;对照组使用生理盐水替代。每组随机取4只小鼠,病理检查;每组剩余6只小鼠取其鼻黏膜,实时定量PCR检测小鼠鼻黏膜中miR-150及IRAK2 mRNA表达水平,蛋白印迹法(Western blot)检测IRAK2蛋白的表达,采用酶联免疫吸附法(ELISA)测定血清中OVA特异性IgE、IL-4、IL-13的含量,模型组与对照组miR-150相对表达量与IRAK2 mRNA的相对表达量、OVA特异性IgE、IL-4、IL-13的相关性分析采用Pearson相关性分析。结果AR组小鼠动物行为学评分均大于5分;病理组织HE染色显示AR组鼻黏膜纤毛大量脱落,组织间质水肿、小血管扩张、腺体增生、炎性细胞浸润;血清OVA特异性IgE、IL-4、IL-13表达增加。AR组小鼠鼻黏膜miR-150表达较NC组降低(P<0.05);IRAK2 mRNA表达水平明显高于对照组(P<0.05);且AR组鼻黏膜IRAK2蛋白表达水平也比NC组增加(P<0.05)。AR组与NC组miR-150相对表达量与IRAK2 mRNA表达量和OVA特异性IgE、IL-4、IL-13的含量呈负相关(r=-0.841、-0.869、-0.834、-0.857,P<0.05)。结论miR-150在变应性鼻炎模型小鼠中表达降低且与IRAK2、OVA特异性IgE、IL-4、IL-13含量存在负相关,二者的表达差异可能在变应性鼻炎的发生发展中发挥作用。     

卵巢癌发生发展关键基因的生物信息学筛选

目的筛选影响卵巢癌发生发展的关键基因,并分析其作用机制。方法利用高通量基因表达(GEO)数据库、癌症基因图谱(TCGA)数据库及KMplot数据库筛选卵巢癌关键基因,分析其与患者临床病理学特征的关系,同时使用GESA进行信号通路聚类分析,并使用TIMER数据库确定与之密切相关的基因,通过STRING数据库绘制互作网络图,预测其作用机制。结果通过筛选共得到13个差异基因,其中ARX和FAM150B与患者预后有关,且其表达量越低,患者总生存期越短(P<0.01)。进一步分析发现ARX和FAM150B的表达量还与IL-6、PIK3R2、PIK3CD、VAV1、PIK3CA、RAC2、PIK3R1及MAPK1的表达量相关(P<0.05)。使用STRING数据库分析发现ARX和FAM150B通过TUBA1A、EGFR、PLXNA2对以上基因进行调控。结论ARX和FAM150B在卵巢癌组织中呈低表达状态,它们的表达量和患者的预后密切相关。ARX和FAM150B可对一系列基因进行调控,从而减弱机体的抗肿瘤免疫反应,促进卵巢癌的发生发展。     

血清miR-150、IL-18水平有助于评估脓毒症休克患者的预后

摘要 目的：探讨脓毒症休克患者血清中微小RNA-150（miR-150）、白细胞介素-18（IL-18）水平，与脓毒症休克的关系。方法：选取2017年3月-2020年3月海南医学院第一附属医院住院的脓毒症患者115例，按照病情严重程度分为脓毒症组(83例)和脓毒症休克组（32例），选取同期体检健康者120例作为对照组。根据3个月预后结果将脓毒症休克组患者分为预后良好组（23例）和预后不良组（9例）。采用实时荧光定量PCR（qRT-PCR）法检测所有受试者血清miR-150水平，采用酶联免疫吸附试验（ELISA）检测所有受试者血清IL-18水平，Pearson分析脓毒症休克组患者miR-150、IL-18水平与实验室指标及评分的相关性，采用Logistic回归分析影响脓毒症休克患者预后的因素。结果：对照组、脓毒症组、脓毒症休克组白细胞计数（WBC）、C反应蛋白（CRP）、丙氨酸转氨酶（ALT）、降钙素原（PCT）水平依次升高，血小板计数（PLT）水平依次降低（P均＜0.05）；脓毒症休克组病程长于脓毒症组；天门冬氨酸转氨酶（AST）、中性粒细胞与淋巴细胞比值（NLR）、序贯器官功能衰竭评估（SOFA）评分、急性生理与慢性健康状态评估（APACHE Ⅱ）评分高于脓毒症组（P均＜0.05）；对照组、脓毒症组、脓毒症休克组血清miR-150表达水平依次降低，而IL-18水平依次升高（P均＜0.05）；脓毒症休克组患者miR-150与CRP、NLR、SOFA评分、APACHEⅡ评分、IL-18呈负相关（P均＜0.05）；IL-18与WBC、CRP、NLR、APACHE Ⅱ评分呈正相关，与PLT呈负相关（P均＜0.05）；与预后良好组比较，预后不良组血清miR-150表达水平更低，IL-18水平更高（P均＜0.05）；血清CRP、IL-18高水平及miR-150低水平是影响脓毒症休克患者预后的危险因素。结论：脓毒症休克患者血清中miR-150呈低表达、IL-18呈高表达，且与患者不良预后有一定关系。     

基于血清ADAMTS13、miR-150、miR-375建立高龄急性心肌梗死患者术后生存状况预测模型的研究

目的 探讨血清血管性血友病因子裂解蛋白酶(von Willebrand factor lytic protease, ADAMTS13)、miR-150、miR-375预测高龄急性心肌梗死(acute myocardial infarction, AMI)患者术后生存状况价值。方法 选取2019年3月至2021年3月行经皮冠脉介入术(percutaneous coronary intervention, PCI)治疗的342例高龄AMI患者,根据术后12个月生存状况分为存活组和死亡组。比较两组一般资料、血清ADAMTS13、miR-150、miR-375水平,采用Cox回归方程分析高龄AMI患者术后生存状况影响因素,绘制列线图模型,采用校准曲线及受试者操作特征(receiver operating characteristic, ROC)曲线判断血清各指标、预测模型诊断效果,采用Kaplan-Meier曲线分析血清各指标不同表达生存状况。结果 死亡组血清ADAMTS13水平低于存活组,miR-150、miR-375水平及NYHA分级、冠状动脉病变支数所占比例高于存活组(P均<0....     

心力衰竭患者再同步化治疗反应性及预后相关因素的分析

目的:对接受再同步化治疗(CRT)患者的临床特征进行比较,分析CRT反应和预后的影响因素。方法:纳入2013-02-2018-02在福建省立医院接受CRT-P/D治疗的72例患者,随访13.5个月(3～66个月),根据术后心脏彩超指标将CRT应答分为无反应、有反应和超反应组,观察3组在临床特征及预后等方面的差异。结果:72例患者中,无反应组22例,有反应组19例,超反应组31例。超反应组中女性(48.4%)、QRS≥150 ms患者(67.7%)比例较高;有反应组中非缺血性心肌病(NICM)患者(89.5%)比例较高;无反应组中则心房颤动或心房扑动(54.5%)、室性心律失常(63.6%)者较多(P0.05)。左束支传导阻滞(LBBB)在3个组中的分布虽无统计学意义(P=0.062),但在超反应组中占比高达61.3%。女性、QRS≥150 ms及左室舒张末容积为CRT超反应的独立预测因素。生存分析提示,QRS≥150 ms、CRT超反应及轻中度肾功能不全为预测远期预后良好的重要因素(P0.05)。结论:女性、QRS≥150 ms可作为CRT超反应的独立预测因素,而NICM、LBBB可能与CRT有应答有关,心房颤动或心房扑动及室性心律失常与CRT无反应有关,QRS≥150 ms、CRT超反应者及轻中度肾功能不全患者生存获益明显。     

miR-150-5p对脑小血管病大鼠脑微血管内皮细胞凋亡的影响

目的 分析miR-150-5p对脑小血管病(CSVD)大鼠脑微血管内皮细胞凋亡的影响。方法 56只雄性大鼠14只作为正常组并不做处理，剩余42只建立CSVD模型，建模中途死亡6只。将建模成功的大鼠随机分为模型组、上调组、下调组，每组8只，做miR-150-5p转染，鉴定miR-150-5p转染率、氧化应激指标水平、神经凋亡率和乳酸脱氢酶(LDH)释放率。结果 与正常组、模型组相比，上调组miR-150-5p表达量升高，下调组miR-150-5p表达量降低，具有统计学差异(P<0.05),证明miR-150-5p转染成功。与正常组相比，模型组、下调组细胞凋亡率、LDH释放率、丙二醛(MDA)水平升高，超氧化物歧化酶(SOD)水平降低，上调组细胞凋亡率、LDH释放率、MDA水平降低，SOD水平升高，具有统计学差异(P<0.05);与模型组相比，下调组细胞凋亡率、LDH释放率、MDA水平升高，SOD水平降低，上调组细胞凋亡率、LDH释放率、MDA水平降低，SOD水平升高，具有统计学差异(P<0.05);与上调组相比，下调组细胞凋亡率、LDH释放率、MDA水平升高，SOD水平...     

Chronic pulmonary embolism and pulmonary hypertension

Incomplete resolution of acute pulmonary embolism (PE) is frequently observed after acute PE and may rarely result in chronic thromboembolic pulmonary hypertension (CTEPH). The underlying pathophysiological mechanism is largely unknown. Evidence underlines the concept of a dual pulmonary vascular compartment model consisting of increased pulmonary vascular resistance by both large vessel obstruction and distal small vessel obliteration, the latter initiated by pathological vascular remodeling. Up to 40% of patients with established CTEPH have no prior history of symptomatic venous thromboembolism. CTEPH is associated with a poor prognosis if left untreated. Therefore, the diagnostic approach of CTEPH aims at assessing the location and extent of the embolic obstruction, establishing the operability and prognosis of the patients and ruling out other variations of pulmonary hypertension with distinct indicated treatment. Heart catheterization for invasive pressure measurements and pulmonary catheter angiography is obligatory for the final diagnosis. Pulmonary thromboendarterectomy is the treatment of choice. In certain patients with persistent or recurrent pulmonary hypertension after surgery or with inoperable disease, pharmacotherapy might be beneficial.     

肺动脉血栓内膜剥脱术后再灌注肺水肿的进展

肺血栓栓塞症是一种常见、多发且病死率和致残率高的疾病。大多数急性肺动脉血栓栓塞经及时的溶栓抗凝等治疗和 (或 )自身的纤溶系统能将血栓不同程度地溶解 ,另有0 1%～ 0 2 %的患者因血栓在急性期未能溶解或栓塞反复发生进而发展成慢性栓塞性肺动脉高压。慢性栓塞性肺动脉高压溶栓无效 ,抗凝、扩血管治疗效果不佳 ,其病理过程多呈进行性加重或稳定一段时间后再次加重 ,自然预后差。肺动脉平均压 >3 0ｍｍＨｇ(1ｍｍＨｇ =0 13 3ｋＰａ)的慢性栓塞性肺动脉高压患者 5年生存率为 3 0 % ,肺动脉平均压 >5 0ｍｍＨｇ者仅为 10 %。肺动脉血…     

Chronic solitary pulmonary nodule due to unsuspected pulmonary infarction from silent pulmonary embolism

Abstract A case of pulmonary embolism showing a longstanding solitary pulmonary nodule is presented. An asymptomatic 57 year-old man with a solitary nodule in the right lower lobe was referred to our hospital. A pulmonary perfusion-ventilation scan following a sudden onset of dyspnoea established the diagnosis of recurrent pulmonary embolism. The nodule gradually disappeared after anticoagulant treatment, indicating that the nodule was pulmonary infarction from silent pulmonary embolism. Although the incidence of pulmonary infarction is low in Japan, this case suggests that pulmonary infarction from silent pulmonary embolism should be considered as one important cause of a solitary pulmonary nodule.     

Retrograde pulmonary perfusion improves results in pulmonary embolectomy for massive pulmonary embolism

Mortality rates for pulmonary embolectomy in patients with acute massive pulmonary embolism have decreased in recent years. However, they still range from 30% to 45% when the surgery is performed on critically ill patients, and the rates reach 60% in patients who have experienced cardiac arrest before the procedure. The causes of death in these patients are generally attributed to right heart failure due to persistent pulmonary hypertension, intractable pulmonary edema, and massive parenchymal and intrabronchial hemorrhage. Clinical and experimental findings indicate that venous air embolism causes severe or even lethal damage to the pulmonary microvasculature and the lung parenchyma consequent to the release of endothelium-derived cytokines. These findings are similar to those observed when severely compromised patients undergo pulmonary embolectomy-air entrapped in the pulmonary artery during embolectomy can lead to fatal outcomes.Besides enabling the removal of residual thrombotic material from the peripheral branches of the pulmonary artery, retrograde pulmonary perfusion fills the pulmonary artery with blood and prevents pulmonary air embolism. In this retrospective study, we analyzed a series of 21 consecutive critically ill patients in whom we applied retrograde pulmonary perfusion while performing standard pulmonary embolectomy. No patient died or experienced major postoperative complications. We believe that the use of retrograde pulmonary perfusion decreases morbidity and mortality rates associated with pulmonary embolectomy in critically ill patients.     

Nitroglycerin-responsive pulmonary hypertension in idiopathic pulmonary hemosiderosis

Idiopathic pulmonary hemosiderosis (IPH) is an uncommon disease found predominantly in pediatric patients. It can produce severe chronic pulmonary injury that results in chronic hypoxemia, pulmonary insufficiency, and progressive pulmonary fibrosis, leading to irreversible pulmonary hypertension and death. We studied the pulmonary hemodynamics in an 9-yr-old boy with IPH to determine if pulmonary hypertension contributed to exacerbations of this disease. Our results showed that this patient demonstrated pulmonary hypertension during acute exacerbations. Initially, the elevated pulmonary artery pressure responded both to oxygen and to a pulmonary vasodilator in the form of nitroglycerin. However, this improvement was not sustained. We conclude that pulmonary hypertension is probably a result of chronic hypoxemia experienced by patients with pulmonary hemosiderosis. Further investigation is warranted to assess whether or not intervention aimed at reducing pulmonary artery pressure in IPH improves outcome.     

Reperfusion pulmonary edema after pulmonary artery thromboendarterectomy

Pulmonary artery thromboendarterectomy (PAT) is a potentially curative procedure in chronic, major vessel thromboembolic pulmonary hypertension. However, postoperative reperfusion pulmonary edema (RPE) has been a serious complication, often requiring prolonged mechanical ventilation. This entity has been described only anecdotally in the past. To characterize it more fully, we retrospectively analyzed the course and potential determinants of RPE after thromboendarterectomy in 22 patients who had PAT at our institution from 1969 through 1984. Particular attention was directed to clinical data, thrombus location, areas operated, postoperative roentgenograms, and preoperative and postoperative hemodynamic data. In all patients but 1, RPE developed within 72 h after surgery, corresponding to anatomic locations distal to vessels subjected to PAT. Regions of lung not reperfused at surgery were uniformly spared. Pulmonary capillary wedge and/or left atrial pressures preoperatively and postoperatively were not elevated. None of the preoperative data predicted which patients would develop more persistent RPE. These observations suggest that the phenomenon of RPE is a peculiar, focal form of pulmonary edema, the basis for which remains to be defined.     

Primary pulmonary artery sarcoma mimicking pulmonary thromboembolism

A 69-year-old woman presenting with dyspnea had a pericardial window created for fibrinous pericarditis. The patient subsequently developed pulmonary hypertension and a ventilation perfusion scan was compatible with pulmonary thromboembolism. A primary tumour of the pulmonary artery was suggested by angiography, computerized axial tomography and magnetic resonance imaging. Pathology confirmed a spindle cell pulmonary artery sarcoma.     

Cavitating pulmonary infarcts revealing thromboembolic pulmonary hypertension

Several etiologies are involved in the pathogenesis of cavitating pulmonary disease including neoplastic, infectious or inflammatory processes. Another is pulmonary infarction associated with venous thromboembolism. The lung cavities tend to be located peripherally and are the result of pulmonary embolism. We report the case of a woman with chronic thromboembolic pulmonary hypertension (CTEPH), associated with familial thrombophilia, revealed by cavitating pulmonary infarcts. CTEPH is sometimes diagnosed during an episode of recurrent pulmonary embolism following previously unnoticed lesions. Thrombophilias such as isolated elevated factor VIII are risk factors for CTEPH.     

Acute pulmonary embolism and pulmonary infarction]

32 cases of pulmonary embolism were reported, 18 cases had been autopsied (massive pulmonary embolism 9 cases. moderate pulmonary embolism 23 cases). The incidence risk factors pathogenesis, clinical manifestations of pulmonary embolism were presented. The relation between pulmonary embolism and pulmonary infarction and treatment of massive pulmonary infarction were discussed.