Discovery and Development of LX7101, a Dual LIM-Kinase and ROCK Inhibitor for the Treatment of Glaucoma

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巨噬细胞迁移抑制因子通过CC趋化因子配体2诱导巨噬细胞聚集

巨噬细胞迁移抑制因子最初是由于能抑制体外巨噬细胞随机迁移而被发现,现在它作为一种重要的调节因子参与一系列炎症性疾病过程.我们最近发现,巨噬细胞迁移抑制因子的缺失使一些由炎症介质诱发的白细胞-内皮细胞相互作用减弱,提示巨噬细胞迁移抑制因子在炎症反应中起作用的机制之一是促进白细胞聚集.……     

Syngeneic transplantation with peripheral blood mononuclear cells collected after the administration of recombinant human granulocyte colony-stimulating factor

Five syngeneic transplants were performed in four patients following myeloablative therapy using unmodified peripheral blood mononuclear cells (PBMCs) collected after the administration of recombinant human granulocyte colony stimulating factor (rhG-CSF) to normal donors. The only toxicity experienced by the four normal donors was bone pain. Four patients received two collections of PBMCs, and a second transplant was performed in one patient with one collection. The patients received a median of 20.53 x 10(8) total nucleated cells/kg (range 20 to 25.5), 11.3 x 10(8) total mononuclear cells/kg (range 6.52 to 17.2), 113.1 x 10(4)/kg CFU-GM (range 46.7 to 211.8) and 9.6 x 10(6) CD34+ cells/kg (range 1.6 to 12.6) Post-transplant growth factors were not administered. The median time to an absolute neutrophil count greater than 0.5 x 10(9)/L was 14 days (range 10 to 18). The median time to platelet transfusion independence was 11 days (range 10 to 13). Two patients had the number of CD3+ T lymphocytes determined in the pheresis product. An average of 3.04 x 10(10) CD3+ cells were collected per pheresis. This represents an approximate 1 log increase over the number of T lymphocytes in a typical bone marrow transplant. Rh-GCSF can be used to mobilize peripheral blood progenitor cells from normal donors with minimal toxicity. Studies of allogeneic transplants using PBMCs collected after rhG-CSF administration to determine permanent grafting ability and the incidence and severity of graft-versus-host disease are warranted.     

Retrovirally marked CD34-enriched peripheral blood and bone marrow cells contribute to long-term engraftment after autologous transplantation

We report here on a preliminary human autologous transplantation study of retroviral gene transfer to bone marrow (BM) and peripheral blood (PB)-derived CD34-enriched cells. Eleven patients with multiple myeloma or breast cancer had cyclophosphamide and filgrastim-mobilized PB cells CD34-enriched and transduced with a retroviral marking vector containing the neomycin resistance gene, and CD34-enriched BM cells transduced with a second marking vector also containing a neomycin resistance gene. After high-dose conditioning therapy, both transduced cell populations were reinfused and patients were followed over time for the presence of the marker gene and any adverse effects related to the gene-transfer procedure. All 10 evaluable patients had the marker gene detected at the time of engraftment, and 3 of 9 patients had persistence of the marker gene for greater than 18 months posttransplantation. The marker gene was detected in multiple lineages, including granulocytes, T cells, and B cells. The source of the marking was both the transduced PB graft and the BM graft, with a suggestion of better long-term marking originating from the PB graft. The steady- state levels of marking were low, with only 1:1000 to 1:10,000 cells positive. There was no toxicity noted, and patients did not develop detectable replication-competent helper virus at any time posttransplantation. These results suggest that mobilized PB cells may be preferable to BM for gene therapy applications and that progeny of mobilized peripheral blood cells can contribute long-term to engraftment of multiple lineages.     

河北省儿童医院住院患儿EB病毒感染流行病学特征

目的了解河北省儿童医院住院患儿EB病毒(EBV)感染的流行病学特征,为儿童EBV感染的诊断和预防提供科学依据。方法收集2017年1—12月河北省儿童医院0~14岁EBV感染住院患儿的全血样本,采用酶联免疫吸附试验(ELISA)检测其EBV衣壳抗原(VCA)IgG及IgM抗体,抗早期抗原(EA)IgG抗体和抗核抗原1(NA1)IgG抗体,以检测结果为研究样本的抗体谱。根据4种EBV抗体的检测结果分为现症感染(抗VCA-IgM抗体阳性,抗NA1-IgG抗体阴性、抗VCA-IgG抗体、抗EA-IgG抗体阳性或阴性)、亚急性感染(抗VCA-IgG抗体阳性,抗VCA-IgM抗体、抗NA1-IgG抗体、抗EA-IgG抗体阳性或阴性)、既往感染(抗NA1-IgG抗体阳性,抗VCA-IgG抗体阳性或阴性,其他抗体均为阴性)和未感染(4种抗体均阴性)。按照患儿年龄、检出月份和性别分析各组的阳性率。结果共纳入符合要求的样本4 451例,其中3 257例(73.17%)抗体谱提示EBV感染,包括现症感染380例(8.54%)、亚急性感染616例(13.84%)、既往感染2 261例(50.80%)。不同年龄组原发阳性检出率差异有统计学意义(P<0.05),其中学龄前(>3岁)组的阳性检出率最高(P<0.05);不同检出月份组阳性检出率差异有统计学意义(P<0.05),7月份阳性检出率高于其他月份(P<0.05);男性患儿与女性患儿EBV感染率差异无统计学意义(P>0.05)。380例现症感染患儿的疾病谱以血液系统疾病[传染性单核细胞增多症、急性粒细胞缺乏症、血小板减少性紫癜、EBV相关嗜血细胞综合征]为主,其中传染性单核细胞增多症为临床常见疾病;其次是呼吸系统疾病(急性支气管炎、疱疹性咽峡炎、急性扁桃体炎);其他疾病谱包括神经系统疾病及血流感染、肾病综合征、川崎病。结论河北省儿童医院住院患儿EBV阳性检出率有年龄和检出月份差异,现症感染以血液系统疾病患儿为主,医院应根据流学病学特征制定相应预防措施。     

Further study of the diagnostic and screening efficiency of the ST-depression adjective check lists

In order to provide additional data on the diagnostic efficiency of the DACL in a situation in which dual diagnoses that involve depression also are considered, two groups of psychiatric patients completed DACL list E and independently were assigned psychiatric diagnoses via the Psychiatric Diagnostic Interview. Findings indicate that the DACL may be of considerable use in screening for depression. Sensitivity was high for both males and females (.84 and .80, respectively) with a cutting score of 12/13. Correct classification rates were also between 4 and 10% higher than base rates. © 1996 John Wiley & Sons, Inc.     

Strategies for improving outcomes of COPD exacerbations

COPD is uniquely situated as a chronic disease at the beginning of the 21st century; it is not only an established major cause of mortality and morbidity but is increasing in prevalence despite current medical interventions. In addition COPD is not a stable disease but its natural history is punctuated by periods of acute deterioration or exacerbations. Exacerbations generate considerable additional morbidity and mortality, and directly affect patients’ quality of life. However, despite significant advances in understanding and treating this disease, exacerbations continue to be the major cause of COPD-associated hospitalization, and provision for their management incurs considerable health care costs. This review will consider the current management of COPD exacerbations and how new clinical strategies may improve outcome of these important clinical events.     

Integration of Merged Delayed‐Enhanced Magnetic Resonance Imaging and Multidetector Computed Tomography for the Guidance of Ventricular Tachycardia Ablation: A Pilot Study

MDCT/MRI Fusion for the Guidance of VT Ablation . Background: Delayed enhancement (DE) MRI can assess the fibrotic substrate of scar‐related VT. MDCT has the advantage of inframillimetric spatial resolution and better 3D reconstructions. We sought to evaluate the feasibility and usefulness of integrating merged MDCT/MRI data in 3D‐mapping systems for structure–function assessment and multimodal guidance of VT mapping and ablation. Methods: Nine patients, including 3 ischemic cardiomyopathy (ICM), 3 nonischemic cardiomyopathy (NICM), 2 myocarditis, and 1 redo procedure for idiopathic VT, underwent MRI and MDCT before VT ablation. Merged MRI/MDCT data were integrated in 3D‐mapping systems and registered to high‐density endocardial and epicardial maps. Low‐voltage areas (<1.5 mV) and local abnormal ventricular activities (LAVA) during sinus rhythm were correlated to DE at MRI, and wall‐thinning (WT) at MDCT. Results: Endocardium and epicardium were mapped with 391 ± 388 and 1098 ± 734 points per map, respectively. Registration of MDCT allowed visualization of coronary arteries during epicardial mapping/ablation. In the idiopathic patient, integration of MRI data identified previously ablated regions. In ICM patients, both DE at MRI and WT at MDCT matched areas of low voltage (overlap 94 ± 6% and 79 ± 5%, respectively). In NICM patients, wall‐thinning areas matched areas of low voltage (overlap 63 ± 21%). In patients with myocarditis, subepicardial DE matched areas of epicardial low voltage (overlap 92 ± 12%). A total number of 266 LAVA sites were found in 7/9 patients. All LAVA sites were associated to structural substrate at imaging (90% inside, 100% within 18 mm). Conclusion: The integration of merged MDCT and DEMRI data is feasible and allows combining substrate assessment with high‐spatial resolution to better define structure–function relationship in scar‐related VT. (J Cardiovasc Electrophysiol, Vol. 24, pp. 419‐426, April 2013)