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Lipid nanoparticles deliver mRNA to the blood-brain barrier

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Nano Research 2024年第10期17卷 9126-9134页

作者： Yanina Kuzminich Avraham Shakked Randi calkins Sebastian Rudden Camille jones jessie Doan Bora jang Elisa Schrader Echeverri Ryan Zenhausern Liming Lian david Loughrey Hannah E.Peck Rachelle Wiese Dorothy Koveal Philip j.Santangelo james E.Dahlman George C.Woodruff School of Mechanical Engineering Georgia Institute of TechnologyAtlantaGA 30332USA Parker H.Petit Institute for Bioengineering and Biosciences Georgia Institute of TechnologyAtlantaGA 30332USA Wallace H.Coulter Department of Biomedical Engineering Emory University School of Medicine and Georgia Institute of TechnologyAtlantaGA 30332USA

Lipid nanoparticles(LNPs)have delivered RNA to hepatocytes in patients after intravenous *** clinical data support efforts to design LNPs that transfect cells in the central nervous system(CNS).However,delivery to the CNS has been difficult,in large part because quantifying on-target delivery alongside common off-target cell types in adult mice remains *** we report methods to isolate different cell types from the CNS,and subsequently present mRNA delivery readouts using a liver-detargeted *** data suggest that LNPs without targeting ligands can transfect cerebral endothelial cells in mice after intravenous *** the difficulty of crossing the blood-brain barrier,they also underscore the value of quantifying delivery in the CNS with cell-type resolution instead of whole-tissue resolution.

关键词： lipid nanoparticle mRNA nanomedicine central nervous system blood-brain barrier

阑尾炎穿孔时的一种简单且成本效益比更高的抗生素用法

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世界核心医学期刊文摘（儿科学分册） 2006年第A10期2卷 35-36页

作者： St. Peter S.D. Little D.C. calkins C.M. D.j. Ostlie 刘凯 Department of Pediatric Surgery The Children' sMercy Hospital Kansas City MO 64108 United States

Objective: Appendicitis is the most common abdominal emergency in children. When perforation is encountered, postoperative management is grounded upon the use of intravenous antibiotics. The 3- drug regimen of ampicillin, gentamicin, and clindamycin has long been the accepted standard by pediatric surgeons. Although effective and seemingly inexpensive, this regimen produces a cumbersome dosing schedule, which has inspired the search for a simpler regimen that does not compromise efficacy or expense. To this end, we have introduced a 2- drug regimen of ceftriaxone and Flagyl (Pharmacia Corporation, Chicago, Ill) with once- a- day dosing. Methods: A retrospective review was conducted of the most recent 250 patients treated at our institution with perforated appendicitis. Patients treated since the implementation of this 2- drug regimen were compared with the recent historical cohort treated with triple antibiotic coverage. Parameters analyzed between the 2 groups included temperature curves for the first 5 postoperative days, abscess rate, length of hospitalization, length of intravenous antibiotic treatment, and medication charges. Results: The 2- drug regimenwas used in 57 patients (group 1) compared with 193 patients treated with triple antibiotic coverage (group 2). Maximum recorded temperature between the 2 groups was similar upon admission, but the mean maximum temperature in group 1 became significantly lower than group 2 from postoperative day 1 onward (P < 0.001). Postoperatively, an abscess developed in 8.8% of group 1 compared with 14.2% of group 2, which was not significantly different (P = 0.37). Mean length of stay was 6.8 days in group 1 and 7.8 days in group 2 (P = 0.03). Medication charges to the patient were ＄ 81.32 per day in group 1 compared with ＄ 318.53 per day in group 2, translating to ＄ 1186.05 savings for 5 days. Conclusions: Once- a- day dosing with ceftriaxone and Flagyl provides adequate antibiotic coverage for the postoperative management

关键词：阑尾炎穿孔给药方案药物联合应用药物联合治疗氯林可霉素术后治疗小儿外科药物联用形成率

致心律失常性右心室发育不良/心肌病患者的心电图随访发现

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世界核心医学期刊文摘（心脏病学分册） 2005年第11期1卷 35-35页

作者： Piccini j. P. Nasir K. Bomma C. H. calkins 姜朝晖 Division of Cardiology Department of Medicine Johns Hopkins Medical Institutions Baltimore MD United States Dr.

Thirty-five patients with arrhythmogenic right ventricular dysplasia/ cardiomyopathy underwent serial electrocardiographic(ECG) testing and were evaluated for evidence of ECG progression. Over a median of 43 months, 89%of the patients had evidence of progression, with S-wave prolongation being the most prevalent marker of ECG progression.

关键词：致心律失常性心肌病患者心室发育不良

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微创性漏斗胸修复术后感染的处理

世界核心医学期刊文摘（儿科学分册） 2005年第12期1卷 45-45页

作者： calkins C.M. Shew S.B. Sharp R.j. G.W. Holcomb III 王经纬 Department of Surgery Children's Mercy Hospital University of Missouri at Kansas City School of Medicine Kansas City MO 66408 United States

Pectus excavatum is frequently repaired using the minimally invasive placement of a substernal bar (Nuss procedure). Infectious complications after the Nuss procedure are potentially devastating. To date, the management of postoperative infectious complications has not been well described. Methods: A retrospective review of all patients (N = 168) who underwent the Nuss procedure from january 1, 1997, to October 1, 2003, at our institution was performed. Six patients (4% ) had postoperative infections, and their medical records were reviewed. Results: Of the 6 patients, 5 underwent operative drainage for wound abscesses that developed 2 to 76 weeks postoperatively. The other patient developed cellulitis 12 months postoperatively and was treated effectively with antibiotics alone. Recurrent infections were treated in 3 of 6 patients, one of whom eventually required removal of the bar resulting in a mild, residual pectus excavatum defect. One of 6 patients has had the substernal bar removed electively. The remaining 4 continue to be without clinically apparent infection at this time and are over 1 year removed from their infection. Conclusions: Although uncommon, infectious complications after the Nuss procedure require complex management strategies. Despite recurrent infection in some cases, most infectious complications occurring after the minimally invasive repair can be effectively treated without having to remove the substernal bar.

关键词：漏斗胸微创性术后感染感染并发症医疗记录脓肿引流蜂窝织炎手术切口连接杆日至

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外科根治术治疗抗放射治疗之子宫颈癌症

中华妇产科杂志 1958年第3期06卷 315-316页

作者： j.D.Thompson C.B.Brack 卢大明

john Hopkins Hospital 自从1940年将妇科镭锭治疗门诊改组以来,给予零期子宫颈癌患者施行改良瓦登氏手术(不割除淋巴结),将Ⅰ至Ⅳ期患者施以镭锭及深度 X 光的综合治疗,而发现了有抗放射治疗之子宫颈癌症,这些患者都经过一月或数月足...

john Hopkins Hospital 自从1940年将妇科镭锭治疗门诊改组以来,给予零期子宫颈癌患者施行改良瓦登氏手术(不割除淋巴结),将Ⅰ至Ⅳ期患者施以镭锭及深度 X 光的综合治疗,而发现了有抗放射治疗之子宫颈癌症,这些患者都经过一月或数月足量的放射治疗而经病理的证实无效者。某些学者认为再次应用放射治疗对于抗放射之子宫颈癌及子宫旁组织以及盆腔壁的复发可以治疗,但 Truelson 报告再次照射其五年治愈率仅2%,calkins 在233例再次放射病例中只有

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