Immunogenicity and protective efficacy of adenoviral and subunit RSV vaccines based on stabilized prefusion F protein in pre-clinical models

Respiratory Syncytial Virus (RSV) remains a leading cause of severe respiratory disease for which no licensed vaccine is available. We have previously described the derivation of an RSV Fusion protein (F) stabilized in its prefusion conformation (preF) as vaccine immunogen and demonstrated superior immunogenicity in naive mice of preF versus wild type RSV F protein, both as protein and when expressed from an Ad26 vaccine vector. Here we address the question if there are qualitative differences between the two vaccine platforms for induction of protective immunity. In naïve mice, both Ad26.RSV.preF and preF protein induced humoral responses, whereas cellular responses were only elicited by Ad26.RSV.preF. In RSV pre-exposed mice, a single dose of either vaccine induced cellular responses and strong humoral responses. Ad26-induced RSV-specific cellular immune responses were detected systemically and locally in the lungs. Both vaccines showed protective efficacy in the cotton rat model, but Ad26.RSV.preF conferred protection at lower virus neutralizing titers in comparison to RSV preF protein. Factors that may contribute to the protective capacity of Ad26.RSV.preF elicited immunity are the induced IgG2a antibodies that are able to engage Fcγ receptors mediating Antibody Dependent Cellular Cytotoxicity (ADCC), and the induction of systemic and lung resident RSV specific CD8 + T cells. These data demonstrate qualitative improvement of immune responses elicited by an adenoviral vector based vaccine encoding the RSV preF antigen compared to the subunit vaccine in small animal models which may inform RSV vaccine development.     

Infective Endocarditis Due to Treponema pallidum: A Case Diagnosed Using Polymerase Chain Reaction Analysis of Aortic Valve

Syphilis is a sexually transmitted disease caused by Treponema pallidum. Syphilitic aortitis might coexist in a dysfunctional aortic valve, but the etiology remains unclear, because microbiological diagnosis is difficult. A 62-year-old man with low-grade fever was diagnosed with aortitis and infective endocarditis, due to Treponema pallidum infection, using polymerase chain reaction analysis. This case suggests that syphilis might cause infective endocarditis.     

膝关节前外侧韧带的研究进展

目的对膝关节前外侧韧带（anterolateral ligament，ALL）的研究进展进行综述，为临床诊治提供参考。方法广泛查阅近年来国内外有关 ALL 损伤诊断及治疗的文献，总结膝关节 ALL 解剖形态、生物力学以及 ALL 损伤机制、治疗现状。结果膝关节 ALL 具有限制胫骨内旋及前移作用，影响膝关节轴移。ALL 损伤后可结合患者体征和 MRI 检查诊断。膝关节 ALL 手术指征尚未统一，但多数学者倾向于对需进行前交叉韧带（anterior cruciate ligament，ACL）重建或翻修且伴有高度轴移试验阳性的患者进行 ALL 重建。目前 ALL 重建方式较多，但尚无最佳治疗术式。此外，由于缺乏高质量的术后长期随访研究，远期临床疗效仍不明确。结论ALL 在维持膝关节稳定性方面具有一定作用，但 ALL 重建技术及临床疗效仍待进一步研究。     

两种技术修复肘关节恐怖三联征中外侧副韧带复合体的疗效比较

目的比较穿骨隧道缝合固定和锚钉固定修复肘关节恐怖三联征中外侧副韧带复合体（lateral collateral ligament complex，LCLC）损伤的疗效。方法回顾分析 2012 年 6 月—2018 年 1 月收治的 50 例肘关节恐怖三联征患者临床资料，其中 22 例采用锚钉固定（锚钉组）、28 例采用穿骨隧道缝合固定（穿骨隧道组）修复 LCLC。两组患者性别、年龄、骨折侧别、受伤至入院时间以及冠状突骨折、桡骨头骨折及肘关节恐怖三联征分型等一般资料比较，差异均无统计学意义（P>0.05）。记录并比较两组手术时间、术中出血量、骨折愈合时间以及并发症发生情况，末次随访时 Mayo 肘关节评分系统（MEPS）、关节活动度、Broberg-Morrey 分级。 结果两组患者均顺利完成手术，手术时间及术中出血量比较差异均无统计学意义（P>0.05）。 患者均获随访，穿骨隧道组随访时间为（24.43±6.84）个月，锚钉组为（21.55±6.16）个月，差异无统计学意义（t=1.534，P=0.132）。X 线片复查示，两组冠状突及桡骨头骨折均愈合，愈合时间组间比较差异无统计学意义（P>0.05）。末次随访时，两组肘关节屈伸活动度、旋转活动度、MEPS 评分、Broberg-Morrey 分级比较，差异均无统计学意义（P>0.05）。随访期间患者均无肘关节再脱位或不稳发生，穿骨隧道组并发症发生率为 28.57%（8/28）、锚钉组为 27.27%（6/22），差异无统计学意义（χ²=2.403，P=0.121）。 结论治疗肘关节恐怖三联征时，采用穿骨隧道固定或锚钉固定修复 LCLC 均可获得满意疗效。     

带蒂大网膜瓣在乳腺癌术后乳房再造中的应用研究

目的探讨带蒂大网膜瓣在乳腺癌术后乳房再造中的临床应用。方法2013 年 5 月—2017 年 10 月，对 205 例乳腺癌患者行改良根治术联合带蒂大网膜瓣移植再造乳房。患者均为女性；年龄 26～58 岁，平均 34.9 岁。左侧 127 例、右侧 78 例；肿瘤直径 2～5 cm，平均 2.9 cm。乳腺癌分期：Ⅰ期 120 例，Ⅱ期 85 例。病理诊断：浸润性导管癌 126 例，浸润性小叶癌 79 例。病程 10～92 d，平均 38.5 d。肿物切除后遗留缺损范围为 9 cm×6 cm～18 cm×12 cm。带蒂大网膜瓣切取范围为 18 cm×10 cm～22 cm×16 cm。结果根据术中观察的组织特点，将大网膜分为 4 种类型，稀薄型（42 例，20.5%）、中间型（133 例，64.9%）、肥厚型（24 例，11.7%）、缺如型（6 例，2.9%）。术后带蒂大网膜瓣均成活，切口Ⅰ期愈合。患者均获随访，随访时间 6～74 个月，平均 24.5 个月；其中 83 例随访达 5 年以上。再造乳房外形可、弹性好，无挛缩变形。供区仅遗留线性瘢痕，腹部功能无影响。随访期间无乳腺癌复发。结论带蒂大网膜瓣切取安全可靠、质地优良，是乳腺癌术后乳房再造的理想方法之一。     

Another look at returns to birthweight

We revisit the causal effect of birthweight. Because variation in birthweight in developed countries primarily stems from variation in gestational age rather than intrauterine growth restriction, we depart from the widely-used twin fixed-effects estimator and employ an instrumental variable – the diagnosis of placenta previa, which provides exogenous variation in gestation length. We find protective effects of additional birthweight against infant mortality and health capital loss, such as cerebral palsy, but in contrast to sibling and twin studies, no strong evidence for non-health long-run outcomes, such as test scores. We also find that short-run birthweight effects have diminished significantly over the decades.     

miR-26b通过调节Notch1信号通路参与原发性肝细胞肝癌侵袭的机制研究

目的:探讨miR-26b参与原发性肝细胞肝癌（HCC）侵袭的机制。方法:在细胞培养液中培养人肝细胞系HL-7702和HCC细胞各系Hepb-3、HuH-7、MHCC97-L、MHCC97-H。实时荧光定量PCR法（qRT-PCR）检测miR-26b的表达水平；用miR-26b mimics、miR-26b inhibitors和Notch1-siRNA分别转染HCC细胞；MTT实验检测转染后HCC细胞的活力；采用Western blot检测Notch1受体蛋白表达水平的变化；Transwell小室测定不同处理后的HCC细胞的侵袭能力。结果:人正常肝细胞系HL-7702和HCC细胞系Hepb-3、HuH-7、MHCC97-L、MHCC97-H中的miR-26b相对表达含量随其侵袭和迁移能力的升高而依次下降；抑制miR-26b的表达，Notch1受体蛋白表达明显增高，而此时HCC细胞的侵袭性显著增强；相反，上调miR-26b的表达，Notch1受体蛋白表达明显降低，而HCC细胞侵袭性显著下降；miR-26b可能通过调控Notch1信号通路调节HCC细胞侵袭性。结论:miR-26b通过负调控Notch1信号通路抑制HCC细胞侵袭能力，为HCC侵袭的机制奠定了理论基础，miR-26b可能成为HCC治疗的新靶点。     

ACEMg supplementation ameliorates progressive Connexin 26 hearing loss in a child

Mutations in the gene encoding Connexin 26 are the most common cause of genetic hearing loss. The hearing loss is typically stable but may be progressive. The reason for progression is unknown. Antioxidants have been associated with attenuation of hearing loss from other insults. One antioxidant regimen consists of beta-carotene (metabolized to vitamin A), vitamin C, vitamin E, and magnesium (ACEMg). We present a child with Connexin 26 related hearing loss who experienced progressive hearing loss over 7 years of observation. He was given ACEMg daily for 3 years, during which time his progressive hearing loss was ameliorated.     

后交叉韧带重建中转角效应：力学机制与临床改良

目的总结后交叉韧带（posterior cruciate ligament，PCL）重建中转角效应的研究进展。方法查阅近年来国内外 PCL 重建中转角效应相关研究，并进行总结。结果研究表明转角效应是导致 PCL 重建术后移植物松弛的主要原因。目前临床上主要通过改变骨隧道固定方式、改变骨隧道方位以及挤压螺钉辅助固定、保留韧带残端、打磨骨隧道口骨质等方式来减小该效应，但缺乏长期临床随访结果。结论针对转角效应的改进方法仍存在较大争议，需要更深入的基础研究，进一步探索重建后 PCL 磨损机制。