Geldanamycin is effective in the treatment of herpes simplex virus epithelial keratitis in a rabbit model

Background: To evaluate the efficacy of geldanamycin eye drops against herpes simplex virus epithelial keratitis in a rabbit model. Methods: New Zealand white rabbits were randomized into four groups and infected with herpes simplex virus type 1; geldanamycin topical eye drops was initiated 24 h after the infection and maintained for 12 consecutive days. Four groups of rabbits received 5 µg/mL geldanamycin, 10 µg/mL geldanamycin, 0.1% acyclovir and escipient (a kind of artificial tears), respectively. The severity of herpes simplex virus type 1 epithelial keratitis was measured by slit‐lamp and scored for statistics analysis. The virus shedding in eye swabs was isolated, and tissue culture infective dose (TCID₅₀) was determined. Results: Geldanamycin (10 µg/mL) treatment reduced significantly the severity of herpes simplex virus type 1 epithelial keratitis than the other three groups. Geldanamycin (5 µg/mL) was as effective as acyclovir (0.1%) treatment. The effect of geldanamycin against herpes simplex virus type 1 epithelial keratitis correlated with accelerated clearance of virus of the rabbits. Conclusion: Geldanamycin is a promising treatment option against herpes simplex virus type 1 epithelial keratitis. Geldanamycin (10 µg/mL) is better than acyclovir and geldanamycin (5 µg/mL) in the rabbit model. The optimal concentration of this drug in human is still to be determined.     

Rhabdomyoma of the orbit

The authors describe a rare case of orbital rhabdomyoma in a 3-year-old girl who presented with progressive proptosis of the left eye. An axial computed tomographic scan of the left orbit demonstrated an irregular retrobulbar mass. The tumor was resected locally from the lateral wall of the orbit and the resected specimens were diagnosed as orbital rhabdomyoma. The authors review the literature and discuss the diagnostic implications and treatment strategies.     

托泊替康与伊立替康单药治疗老年小细胞肺癌的疗效观察

目的：观察托泊替康（TPT）和伊立替康（CPT－11）单药治疗老年小细胞肺癌的疗效及安全性。方法：50例老年小细胞肺癌患者,随机分为两组,分别给予TPT 1．2mg／m2静脉点滴第1～5天;CPT－1165mg／m2第1天和第8天静脉点滴化疗,3周一个化疗周期,共进行2～6周期。治疗开始后随访6～20个月,记录两组患者的白细胞计数、延迟性腹泻、肝功能、血小板计数、贫血等资料,评价近远期疗效,观察二者在疗效和安全性方面的差异。结果：两组患者在完全缓解（CR）、部分缓解（PR）、稳定（SD）、进展（PD）、客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）等方面无统计学差异（P＞0．05）;TPT组白细胞减少比例（64％）高于CPT－11组（32％）,有统计学差异（P＝0．048）,而CPT－11组延迟性腹泻发病率（64％）显著高于TPT组（20％）,差异具有统计学意义（P＝0．004）。结论：托泊替康和伊立替康单药治疗老年小细胞肺癌的近远期疗效无差异,伊立替康组骨髓抑制轻于托泊替康组,但胃肠道不良反应比托泊替康重。     

Phase I study of CAR-T cells with PD-1 and TCR disruption in mesothelin-positive solid tumors

Programmed cell death protein-1 (PD-1)-mediated immunosuppression has been proposed to contribute to the limited clinical efficacy of chimeric antigen receptor T (CAR-T) cells in solid tumors. We generated PD-1 and T cell receptor (TCR) deficient mesothelin-specific CAR-T (MPTK-CAR-T) cells using CRISPR-Cas9 technology and evaluated them in a dose-escalation study. A total of 15 patients received one or more infusions of MPTK-CAR-T cells without prior lymphodepletion. No dose-limiting toxicity or unexpected adverse events were observed in any of the 15 patients. The best overall response was stable disease (2/15 patients). Circulating MPTK-CAR-T cells peaked at days 7–14 and became undetectable beyond 1 month. TCR-positive CAR-T cells rather than TCR-negative CAR-T cells were predominantly detected in effusion or peripheral blood from three patients after infusion. We further confirmed the reduced persistence of TCR-deficient CAR-T cells in animal models. Our results establish the preliminary feasibility and safety of CRISPR-engineered CAR-T cells with PD-1 disruption and suggest that the natural TCR plays an important role in the persistence of CAR-T cells when treating solid tumors.     

Resting cerebral blood flow alteration in severe obstructive sleep apnoea: an arterial spin labelling perfusion fMRI study

Study objectives

The aim of this study is to investigate changes in regional cerebral blood flow (rCBF) in awake people with untreated severe obstructive sleep apnoea (OSAs) compared with good sleepers (GSs).

Design

Arterial spin labelling perfusion imaging was used to quantify cerebral perfusion based on resting-state functional magnetic resonance imaging (MRI).

Setting

Lying supine in a 3.0-T magnetic resonance imaging scanner in the night was done.

Participants

Included in this study were 30 subjects with OSA (males; mean age 38.4 years, range 25–55) and 30 controls (males; mean age: 38.3 years, range 26–52) matched for age and years of education.

Results

Compared with GSs, participants with severe OSA had reduced rCBF in the left cerebellum posterior lobe, left temporal lobe, right medial frontal gyrus, and bilateral parahippocampal gyrus and increased rCBF in the bilateral superior frontal gyrus. The lower mean CBF in the right parahippocampal gyrus exhibited a significant positive correlation with arousal index (r = 0.365, P = 0.047). The increased mean CBF in the left superior frontal gyrus exhibited a significant positive correlation with the longest apnoea time (r = 0.422, P = 0.020), and the increased mean CBF in the right superior frontal gyrus exhibited a significant positive correlation with the longest apnoea time (r = 0.447, P = 0.013).

Conclusions

Our results show that the altered rCBF pattern in the left cerebellum posterior lobe, left temporal lobe, left medial frontal gyrus, bilateral parahippocampal gyrus and superior frontal gyrus in patients have with severe OSA. The arterial spin labelling perfusion imaging method is a useful non-invasive imaging tool for detection of early changes in the regional cerebral blood flow in patients with OSA.

     

替格瑞洛对经CYP3A4途径代谢的他汀治疗急性冠脉综合征的影响

【】 目的 观察对CYP3A4酶有抑制作用的替格瑞洛联合经CYP3A4酶代谢的阿托伐他汀治疗急性冠脉综合征(acute coronary syndrome,ACS)患者的短期内的安全性及对降脂作用的影响。方法 连续入选2016年1月至2016年6月北京安贞医院急诊科收治的ACS患者共244例,随机分为阿托伐他汀 替格瑞洛组(以下简称为替格瑞洛组)和阿托伐他汀 氯吡格雷组(以下简称为氯吡格雷组)。收集入院24小时内和院外一个月内胆固醇(CHOL)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、肌酸激酶(CK)及血清肌酐(Scr)水平,同时计算LDL-C达标率。结果 替格瑞洛组在肝功能损害、肌肉毒性及肾功能损害的发生率上均高于氯吡格雷组(2.8%比0.7%,1.9%比0.7%,4.47%比3.04%),但差异均未达到统计学意义,P值均大于0.05。在LDL-C达标率上,替格瑞洛组为53.3%,明显高于氯吡格雷组的38.0% (P=0.017,P<0.05)。两组在降低CHOL、TG水平上,替格瑞洛组要略优于氯吡格雷组(18.09%比17.93%,6.23%比2.58%),但差异没有统计学意义,P>0.05。结论 在急性冠脉综合征患者治疗中,短期内替格瑞洛对经肝酶CYP3A4代谢的阿托伐他汀的安全性影响较小,整体安全性较好,且在相同剂量的阿托伐他汀治疗下,替格瑞洛联合阿托伐他汀在LDL-C达标率上更有优势。     

肺炎链球菌肺炎与先天免疫的研究进展

肺炎链球菌(streptococcus;pneumonia)感染后可定植引起局部疾病,亦可扩散引起侵袭性疾病.肺炎链球菌是社区获得性肺炎(community;acquired;pneumonia,CAP)中最常见的病原体,同时也是引起肺炎、脑膜炎和脓毒症等威及生命的感染相关性疾病的主要原因.在全世界范围内,肺炎链球菌感染使病死率上升.近年来,国外关于先天免疫对肺炎链球菌的识别及应答有了很多新的研究.本篇综述总结了先天免疫对肺炎链球菌肺炎免疫应答研究的最新进展.     

以神经系统症状为首发表现的血栓性血小板减少性紫癜的临床分析

目的:探讨以神经系统症状为首发表现的血栓性血小板减少性紫癜(TTP)患者的临床特征及诊治策略,提高对该病的认识。方法:回顾性分析以神经系统症状为突出表现的12例TTP患者的一般资料、临床表现、实验室及影像学检查资料、治疗方法以及转归。结果:神经系统表现多样,主要有头痛、头晕、认知障碍、昏迷等,仅3例头部CT示多发腔隙性脑梗死,余无异常;其余症状有紫癜出血、溶血、发热、肾功能损害等。采用血浆置换、糖皮质激素等治疗,7例有效。结论:以神经系统为首发表现的TTP易发生误诊,我们需提高对该病的认识。血浆置换加糖皮质激素为标准治疗,难治性病例可应用利妥昔单抗或其他免疫抑制剂治疗。