2型糖尿病合并冠心病患者血小板表面CD62P和CD40L的表达水平

目的 探讨2型糖尿病合并冠心病患者血小板表面CD62P和CD40L的表达水平及其和血清高敏C反应蛋白的关系.方法 选择单纯冠心病患者34例、单纯2型糖尿病患者33例、2型糖尿病合并冠心病患者30例及对照者30例,采用流式细胞术分别检测血小板表面CD62P和CD40L的表达水平,并与血清高敏C反应蛋白作相关分析.结果 2型糖尿病合并冠心病组血小板CD62P、CD40L和高敏C反应蛋白水平较对照组、单纯冠心病组及单纯2型糖尿病组显著升高(P<0.01),血小板CD62P和CD40L与血清高敏C反应蛋白水平呈正相关(r分别为0.343和0.495,P均<0.05).结论 2型糖尿病合并冠心病患者的血小板表面CD62P和CD40L表达水平明显升高,并与血清高敏C反应蛋白明显正相关.血小板表面CD62P和CD40L的表达水平可能是预示糖尿病患者合并冠状动脉粥样硬化的重要指标.     

单核细胞和血小板CD40L高表达及血小板CD62P高含量与急性冠脉综合征的关系

目的探讨急性冠脉综合征(ACS)外周血单核细胞和血小板表达CD40L及血小板CD62P含量的变化及意义。方法应用间接免疫荧光流式细胞仪测定患者与对照组血单核细胞和血小板表达CD40L水平及血小板CD62P含量。结果发现急性冠脉综合征患者(ACS)单核细胞和血小板表达CD40水平及血小板CD62P含量均显著高于正常对照者(NS)(P<0.01)和稳定型冠心病患者(SA)(P<0.05或P<0.01)。结论急性冠脉综合征患者外周血单核细胞和血小板表达CD40L及血小板CD62P含量可能与ACS的发生有关,是动脉粥样硬化斑块不稳定的标志。     

糖尿病合并急性冠状动脉综合征患者血小板表面PAC-1和CD62P表达水平

目的探讨糖尿病合并急性冠状动脉综合征患者血小板表面血小板膜糖蛋白Ⅱb/Ⅲa纤维蛋白原受体(PAC-1)和P选择素(CD62P)的表达水平及其与血浆同型半胱氨酸(Hcy)的关系。方法选择单纯急性冠状动脉综合征患者40例、糖尿病合并急性冠状动脉综合征患者24例及对照组30例,采用全血流式细胞术结合三色荧光技术检测血小板表面PAC-1和CD62P的表达水平,并与血浆Hcy作相关性分析。结果糖尿病合并急性冠状动脉综合征患者的血小板PAC-1、CD62P和血浆Hcy水平较对照组明显升高(P0.05),同时血小板CD62P表达水平较单纯急性冠状动脉综合征患者明显升高(P0.05);血小板PAC-1、CD62P与血浆Hcy水平呈正相关(r分别为0.441和0.408,均P0.05)。结论糖尿病合并急性冠状动脉综合征患者血小板表面PAC-1、CD62P表达水平明显升高,并与血浆Hcy呈明显正相关。血小板表面PAC-1和CD62P的表达水平可能对预示糖尿病患者发生血栓事件具有重要的意义。     

PD-L1与记忆性T细胞在肝囊型包虫病患者CD4~+T淋巴细胞中的表达及意义

目的检测程序性死亡受体配体-1(PD-L1)及记忆性T细胞在肝囊型包虫病患者CD4+T淋巴细胞中的表达,探讨其在细粒棘球蚴感染免疫逃避中的作用。方法具有包虫活性的肝包虫病患者42例,健康对照20例,取血,分离PBMC,流式细胞术检测PD-L1(CD274+)、CD45RO+及CD4+CD45RO+CD274+细胞比例,并分析PD-L1与CD45RO的相关性。结果肝囊型包虫病患者PBMC中PD-L1、CD45RO+及CD4+CD45RO+CD274+细胞比例均显著高于健康对照组(P<0.05);肝囊型包虫病患者的PD-L1与CD45RO呈显著正相关(P<0.05),健康对照组二者无显著相关关系(P>0.05)。结论在肝囊型包虫病患者的免疫反应中,PD-L1可能通过记忆性T淋巴细胞发挥促进包虫免疫逃避的作用。     

PAC-1和CD62P在脑梗死急性期的表达

PAC1和CD62P是血小板活化的标志物,流式细胞仪能快速敏感检测PAC1和CD62P。血栓性脑梗死急性期血小板活化,PAC1和CD62P表达增加。心源性脑栓塞急性期的血小板活化状态有待进一步研究。     

Severe SARS-CoV-2 Infection in a Cat with Hypertrophic Cardiomyopathy

Coronavirus disease 19 (COVID-19), has claimed millions of human lives worldwide since the emergence of the zoonotic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China in December 2019. Notably, most severe and fatal SARS-CoV-2 infections in humans have been associated with underlying clinical conditions, including diabetes, hypertension and heart diseases. Here, we describe a case of severe SARS-CoV-2 infection in a domestic cat (Felis catus) that presented with hypertrophic cardiomyopathy (HCM), a chronic heart condition that has been described as a comorbidity of COVID-19 in humans and that is prevalent in domestic cats. The lung and heart of the affected cat presented clear evidence of SARS-CoV-2 replication, with histological lesions similar to those observed in humans with COVID-19 with high infectious viral loads being recovered from these organs. The study highlights the potential impact of comorbidities on the outcome of SARS-CoV-2 infection in animals and provides important information that may contribute to the development of a feline model with the potential to recapitulate the clinical outcomes of severe COVID-19 in humans.     

IFITM3 Inhibits SARS-CoV-2 Infection and Is Associated with COVID-19 Susceptibility

SARS-CoV-2 has become a global threat to public health. Infected individuals can be asymptomatic or develop mild to severe symptoms, including pneumonia, respiratory distress, and death. This wide spectrum of clinical presentations of SARS-CoV-2 infection is believed in part due to the polymorphisms of key genetic factors in the population. In this study, we report that the interferon-induced antiviral factor IFITM3 inhibits SARS-CoV-2 infection by preventing SARS-CoV-2 spike-protein-mediated virus entry and cell-to-cell fusion. Analysis of a Chinese COVID-19 patient cohort demonstrates that the rs12252 CC genotype of IFITM3 is associated with SARS-CoV-2 infection risk in the studied cohort. These data suggest that individuals carrying the rs12252 C allele in the IFITM3 gene may be vulnerable to SARS-CoV-2 infection and thus may benefit from early medical intervention.     

CD4 and CD8 Lymphocyte Counts as Surrogate Early Markers for Progression in SARS-CoV-2 Pneumonia: A Prospective Study

Background: COVID-19 pathophysiology and the predictive factors involved are not fully understood, but lymphocytes dysregulation appears to play a role. This paper aims to evaluate lymphocyte subsets in the pathophysiology of COVID-19 and as predictive factors for severe disease. Patient and methods: A prospective cohort study of patients with SARS-CoV-2 bilateral pneumonia recruited at hospital admission. Demographics, medical history, and data regarding SARS-CoV-2 infection were recorded. Patients systematically underwent complete laboratory tests, including parameters related to COVID-19 as well as lymphocyte subsets study at the time of admission. Severe disease criteria were established at admission, and patients were classified on remote follow-up according to disease evolution. Linear regression models were used to assess associations with disease evolution, and Receiver Operating Characteristic (ROC) and the corresponding Area Under the Curve (AUC) were used to evaluate predictive values. Results: Patients with critical COVID-19 showed a decrease in CD3+CD4+ T cells count compared to non-critical (278 (485 IQR) vs. 545 (322 IQR)), a decrease in median CD4+/CD8+ ratio (1.7, (1.7 IQR) vs. 3.1 (2.4 IQR)), and a decrease in median CD4+MFI (21,820 (4491 IQR) vs. 26,259 (3256 IQR)), which persisted after adjustment. CD3+CD8+ T cells count had a high correlation with time to hospital discharge (PC = −0.700 (−0.931, −0.066)). ROC curves for predictive value showed lymphocyte subsets achieving the best performances, specifically CD3+CD4+ T cells (AUC = 0.756), CD4+/CD8+ ratio (AUC = 0.767), and CD4+MFI (AUC = 0.848). Conclusions: A predictive value and treatment considerations for lymphocyte subsets are suggested, especially for CD3CD4+ T cells. Lymphocyte subsets determination at hospital admission is recommended.     

CD62P、PAC-1在AECOPD中的意义

目的探讨血小板活化标志物CD62P、PAC-1在AECOPD中的意义。方法收集本院住院诊断为COPD急性加重期和稳定期患者各30例,另选同期本院健康体检者30例作为对照组。运用流式细胞仪检测以上各组血小板活化标记物PAC-1、CD62P的水平。结果 AECOPD患者CD62P、PAC-1水平高于稳定期患者和健康对照组(P0.05),稳定期患者血小板活化标志物水平高于正常对照组(P0.05)。结论 AECOPD患者存在血小板的活化,CD62P、PAC-1可指导医生及早采取措施,配合使用血小板活化抑制剂和适当的抗凝治疗,对降低血栓的发生率具有重要意义。     

阿托伐他汀、阿司匹林对高血压患者血小板微粒CD62p、CD40L的影响

目的:探讨血小板膜糖蛋白微粒CD62p、CD40L与高血压的关系,以及他汀类、抗血小板药物对其影响。方法:采用流式细胞术(FCM)及单克隆抗体标记法,检测70例高血压患者(高血压组)、20例健康者(对照组)的血液标本,以20μmol/LADP为激活剂激活血小板,35例服用阿司匹林100mgQD,35例同时服用阿司匹林100mgQD和阿托伐他汀20mgQN,检测高血压患者血小板膜糖蛋白微粒CD62p、CD40L水平及药物对其作用。结果:高血压组CD62p、CD40L的百分率(85.3%±11.8%、69.2%±8.6%)比对照组(52.8%±7.6%、35.2%±5.4%)高(P<0.01),服用阿司匹林组CD62p、CD40L的百分率降至(64.2%±9.3%、47.7%±7.4%)与服药前有显著性差异(P<0.05),同时服用阿司匹林和阿托伐他汀组CD62p、CD40L的百分率降至(49.7%±9.8%、36.2%±5.1%)与服药前及只服用阿司匹林相比均差异有统计学意义(P<0.01)。结论:高血压与血小板膜糖蛋白微粒CD62p、CD40L的表达存在一定的联系,阿司匹林、阿托伐他汀可降低血小板微粒CD62...     

腺苷与AMP579对冠心病患者CD62P表达的影响

目的 探讨不同剂量腺苷与AMP579对冠心病(CHD )患者血小板表面CD62P表达的影响.方法 选择经临床症状、心电图改变及心肌酶学确诊的CHD患者30例及正常健康者15名,采集肘静脉血,分别给予不同剂量的腺苷与AMP579,用双抗体夹心酶联免疫吸附法( ELISA)检测患者及正常人用药前后血小板CD62P表达值.结果 CHD患者的血小板CD62P的表达升高,与正常人比较差异有统计学意义(P<0.05);腺苷和AMP579均能降低CHD患者血小板CD62P的表达,分别与用药前比较差异有统计学意义(P<0.05),但同一药物在450 μmol/L、1 000 μmol/L、3 000 μmol/L 3种浓度下对CD62P表达的影响无统计学意义(P>0.05).结论 CHD的发生可能与CD62P表达升高有关;腺苷和AMP579可通过降低CD62P表达而降低血小板与内皮下基质的黏附,从而起到防止血栓的作用.     

寒潮诱发高血压大鼠卒中发病前CD62p和细胞间黏附分子1的变化

目的研究血小板活化和血管内皮损伤标志物在脑卒中启动中的作用。方法300只SD大鼠分为模型组、假手术组和正常对照组,其中假手术组再分为假手术和假手术+内皮损伤组;模型组再分为高血压组、内皮损伤组和高血压+内皮损伤组;在第12周时使用寒潮箱处理各组大鼠,将各组大鼠再分为寒潮组和非寒潮组,其中寒潮组分别在寒潮前及寒潮后检测CD62p阳性表达率,免疫组织化学检测脑小血管细胞间黏附分子1的表达。结果模型组大鼠CD62p阳性表达率和细胞间黏附分子1的表达量高于正常对照组和假手术组(P<0.05);模型组大鼠经寒潮处理后CD62p阳性表达率和细胞间黏附分子1的表达量明显高于非寒潮组(P<0.05),其中高血压+内皮损伤组CD62p阳性表达率和细胞间黏附分子1的表达量更高(P<0.05)。结论长期的高血压损害了大鼠的内皮系统,而寒潮可以使这种损害加重,使其接近卒中前状态。     

Heterogenous CD8+ T Cell Maturation and ‘Polarization’ in Acute and Convalescent COVID-19 Patients

Background. The adaptive antiviral immune response requires interaction between CD8+ T cells, dendritic cells, and Th1 cells for controlling SARS-CoV-2 infection, but the data regarding the role of CD8+ T cells in the acute phase of COVID-19 and post-COVID-19 syndrome are still limited. Methods.. Peripheral blood samples collected from patients with acute COVID-19 (n = 71), convalescent subjects bearing serum SARS-CoV-2 N-protein-specific IgG antibodies (n = 51), and healthy volunteers with no detectable antibodies to any SARS-CoV-2 proteins (HC, n = 46) were analyzed using 10-color flow cytometry. Results. Patients with acute COVID-19 vs. HC and COVID-19 convalescents showed decreased absolute numbers of CD8+ T cells, whereas the frequency of CM and TEMRA CD8+ T cells in acute COVID-19 vs. HC was elevated. COVID-19 convalescents vs. HC had increased naïve and CM cells, whereas TEMRA cells were decreased compared to HC. Cell-surface CD57 was highly expressed by the majority of CD8+ T cells subsets during acute COVID-19, but convalescents had increased CD57 on ‘naïve’, CM, EM4, and pE1 2–3 months post-symptom onset. CXCR5 expression was altered in acute and convalescent COVID-19 subjects, whereas the frequencies of CXCR3+ and CCR4+ cells were decreased in both patient groups vs. HC. COVID-19 convalescents had increased CCR6-expressing CD8+ T cells. Moreover, CXCR3+CCR6- Tc1 cells were decreased in patients with acute COVID-19 and COVID-19 convalescents, whereas Tc2 and Tc17 levels were increased compared to HC. Finally, IL-27 negatively correlated with the CCR6+ cells in acute COVID-19 patients. Conclusions. We described an abnormal CD8+ T cell profile in COVID-19 convalescents, which resulted in lower frequencies of effector subsets (TEMRA and Tc1), higher senescent state (upregulated CD57 on ‘naïve’ and memory cells), and higher frequencies of CD8+ T cell subsets expressing lung tissue and mucosal tissue homing molecules (Tc2, Tc17, and Tc17.1). Thus, our data indicate that COVID-19 can impact the long-term CD8+ T cell immune response.     

Characterization and Outcomes of SARS-CoV-2 Infection in Patients with Sarcoidosis

To analyze the clinical characteristics and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with sarcoidosis from a large multicenter cohort from Southern Europe and to identify the risk factors associated with a more complicated infection. We searched for patients with sarcoidosis presenting with SARS-CoV-2 infection (defined according to the European Centre for Disease Prevention and Control guidelines) among those included in the SarcoGEAS Registry, a nationwide, multicenter registry of patients fulfilling the American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and Other Granulomatous Disorders 1999 classification criteria for sarcoidosis. A 2:1 age-sex-matched subset of patients with sarcoidosis without SARS-CoV-2 infection was selected as control population. Forty-five patients with SARS-CoV-2 infection were identified (28 women, mean age 55 years). Thirty-six patients presented a symptomatic SARS-CoV-2 infection and 14 were hospitalized (12 required supplemental oxygen, 2 intensive care unit admission and 1 mechanical ventilation). Four patients died due to progressive respiratory failure. Patients who required hospital admission had an older mean age (64.9 vs. 51.0 years, p = 0.006), a higher frequency of baseline comorbidities including cardiovascular disease (64% vs. 23%, p = 0.016), diabetes mellitus (43% vs. 13%, p = 0.049) and chronic liver/kidney diseases (36% vs. 0%, p = 0.002) and presented more frequently fever (79% vs. 35%, p = 0.011) and dyspnea (50% vs. 3%, p = 0.001) in comparison with patients managed at home. Age- and sex-adjusted multivariate analysis identified the age at diagnosis of SARS-Cov-2 infection as the only independent variable associated with hospitalization (adjusted odds ratio 1.18, 95% conficence interval 1.04–1.35). A baseline moderate/severe pulmonary impairment in function tests was associated with a higher rate of hospitalization but the difference was not statistically significant (50% vs. 23%, p = 0.219). A close monitoring of SARS-CoV-2 infection in elderly patients with sarcoidosis, especially in those with baseline cardiopulmonary diseases and chronic liver or renal failure, is recommended. The low frequency of severe pulmonary involvement in patients with sarcoidosis from Southern Europe may explain the weak prognostic role of baseline lung impairment in our study, in contrast to studies from other geographical areas.     

糖尿病并血管病变患者血小板膜糖蛋白CD62p、CD63的表达及血小板四参数的研究

目的 :探讨血小板膜糖蛋白CD62p、CD63的表达及血小板四参数与糖尿病并血管病变患者的关系。　　方法 :采用流式细胞术测定 42例 2型糖尿病并发血管性疾病患者 (糖尿病伴血管病变组 )血小板膜糖蛋白CD62p、CD63的表达 ,同时用自动血细胞计数仪对其进行血小板四参数的测定 ,并与 50例糖尿病不伴血管病变组和 46例正常对照组比较。　　结果 :糖尿病伴血管病变组CD62p (11 64± 3 79) %、CD63 (15 73± 4 2 2 ) %的表达和血小板平均体积 (11 85± 2 3 1)fl等 3指标与正常对照组CD62p (2 2 7± 2 11) % ,CD63 (6 83± 2 85) % ,血小板平均体积 (10 72± 1 63 )fl比较均显著性增高(P值分别为 <0 0 0 1,<0 0 0 1和 <0 0 1) ,血小板计数、血小板压积和血小板分布宽度在两组间差异无统计学意义 (P >0 0 5) ;与不伴血管病变组比较 ,CD62p (10 0 1± 3 65) %和CD63 (14 0 2± 3 87) %也显著性增高 (P <0 0 5) ,血小板平均体积、血小板计数、血小板压积和血小板分布宽度在两组间差异无统计学意义 (P >0 0 5)。结论 :2型糖尿病患者血小板大量活化及其体积的改变促进了血管病变的发生和发展     

Placental Pathology of COVID-19 with and without Fetal and Neonatal Infection: Trophoblast Necrosis and Chronic Histiocytic Intervillositis as Risk Factors for Transplacental Transmission of SARS-CoV-2

The mechanism(s) by which neonates testing positive for coronavirus disease 2019 (COVID-19) acquire their infection has been largely unknown. Transmission of the etiological agent, SARS-CoV-2, from mother to infant has been suspected but has been difficult to confirm. This communication summarizes the spectrum of pathology findings from pregnant women with COVID-19 based upon the infection status of their infants and addresses the potential interpretation of these results in terms of the effects of SARS-CoV-2 on the placenta and the pathophysiology of maternal-fetal infection. Placentas from pregnant women with COVID-19 and uninfected neonates show significant variability in the spectrum of pathology findings. In contrast, placentas from infected maternal-neonatal dyads are characterized by the finding of mononuclear cell inflammation of the intervillous space, termed chronic histiocytic intervillositis, together with syncytiotrophoblast necrosis. These placentas show prominent positivity of syncytiotrophoblast by SARS-CoV-2, fulfilling the published criteria for transplacental viral transmission as confirmed in fetal cells through identification of viral antigens by immunohistochemistry or viral nucleic acid using RNA in situ hybridization. The co-occurrence of chronic histiocytic intervillositis and trophoblast necrosis appears to be a risk factor for placental infection with SARS-CoV-2 as well as for maternal-fetal viral transmission, and suggests a potential mechanism by which the coronavirus can breach the maternal-fetal interface.     

PAC-1和CD62P在脑梗死急性期的表达

PAC-1和CD62P是血小板活化的标志物，流式细胞仪能快速敏感检测PAC-1和CD62P。血栓性脑梗死急性期血小板活化，PAC-1和CD62P表达增加。心源性脑栓塞急性期的血小板活化状态有待进一步研究。     

Brain Inflammation and Intracellular α-Synuclein Aggregates in Macaques after SARS-CoV-2 Infection

SARS-CoV-2 causes acute respiratory disease, but many patients also experience neurological complications. Neuropathological changes with pronounced neuroinflammation have been described in individuals after lethal COVID-19, as well as in the CSF of hospitalized patients with neurological complications. To assess whether neuropathological changes can occur after a SARS-CoV-2 infection, leading to mild-to-moderate disease, we investigated the brains of four rhesus and four cynomolgus macaques after pulmonary disease and without overt clinical symptoms. Postmortem analysis demonstrated the infiltration of T-cells and activated microglia in the parenchyma of all infected animals, even in the absence of viral antigen or RNA. Moreover, intracellular α-synuclein aggregates were found in the brains of both macaque species. The heterogeneity of these manifestations in the brains indicates the virus’ neuropathological potential and should be considered a warning for long-term health risks, following SARS-CoV-2 infection.     

急性心肌梗死患者HbA1c与高敏C反应蛋白、CD62p、纤维蛋白原的关系

目的观察急性心肌梗死患者HbA1c与CD62p、纤维蛋白原（Fib）与炎性因子高敏C反应蛋白（hsc-RP）的关系。方法对象选自2008年1月至2009年3月,年龄45-85岁,符合急性心肌梗死诊断标准的入院患者96例。测定HbA1c、Fib、CD62p与hsC-RP。同时随访6个月后的临床终点事件的发生率及这些指标和临床终点事件的相关性。结果根据HbA1c水平将急性心肌梗死（AMI）患者分为HbA1c增高组（35例）及HbA1c正常组（61例）。HbA1c增高组血小板CD62p、hsC-RP、Fib显著高于HbA1c正常组（P〈0．05）。此外,所有AMI患者HbA1c水平与hsC-RP呈正相关（r=0．37,P〈0．01）;所有AMI患者血小板CD62p与hsC-RP呈正相关（r=0．43,P〈0．01）。HbA1c增高组出现临床终点事件者5例,包括随访6月内的再发AMI,再住院行心肌血管重建术、住院期间及随访期间的心源性死亡者;HbA1c正常组未出现临床终点事件。随访6个月内出现临床终点事件者（5例）与无心脏事件（89例）相比,左室射血分数（P〈0．01）、血hsC-RP（P〈0．05）为影响临床终点事件的因素。结论HbA1c水平可能是影响急性心肌梗死患者病情发展及预后的重要因素。