Novel phenotype of mouse spermatozoa following deletion of nine β-defensin genes

β-defensin peptides are a large family of antimicrobial peptides. Although they kill microbes in vitro and interact with immune cells, the precise role of these genes in vivo remains uncertain. Despite their inducible presence at mucosal surfaces, their main site of expression is the epididymis. Recent evidence suggests that a major function of these peptides is in sperm maturation. In addition to previous work suggesting this, work at the MRC Human Genetics Unit, Edinburgh, has shown that homozygous deletion of a cluster of nine β-defensin genes in the mouse results in profound male sterility. The spermatozoa derived from the mutants had reduced motility and increased fragility. Epididymal spermatozoa isolated from the cauda region of the homozygous mutants demonstrated precocious capacitation and increased spontaneous acrosome reactions compared with those from wild-types. Despite this, these mutant spermatozoa had reduced ability to bind to the zona pellucida of oocytes. Ultrastructural examination revealed a disintegration of the microtubule structure of mutant-derived spermatozoa isolated from the epididymal cauda region, but not from the caput. Consistent with premature acrosome reaction and hyperactivation, spermatozoa from mutant animals had significantly increased intracellular calcium content. This work demonstrates that in vivo β-defensins are essential for successful sperm maturation, and that their disruption alters intracellular calcium levels, which most likely leads to premature activation and spontaneous acrosome reactions that result in hyperactivation and loss of microtubule structure of the axoneme. Determining which of the nine genes are responsible for the phenotype and the relevance to human sperm function is important for future work on male infertility.     

滋阴清热方治疗对甲状腺功能亢进症阴虚火旺证患者疗效、血浆内皮素-1、炎症因子和免疫功能的影响

目的:研究滋阴清热方治疗对甲状腺功能亢进症阴虚火旺证患者疗效、血浆内皮素-1、炎症因子和免疫功能的影响。方法:将广州市花都区妇幼保健院收治的100例甲状腺功能亢进症阴虚火旺证患者分成观察组和对照组。对照组:给患者使用常规药物治疗;观察组:在对照组的基础上,给予滋阴清热方治疗。干预后,比较两组患者的临床疗效、血浆内皮素-1(Endothelin,ET)、炎症因子[白介素-2(Interleukin-2,IL-2)、白介素-8(Interleukin-8,IL-8)]及肿瘤坏死因子(Tumour Necrosis Factor-α,TNF-α)和免疫功能(CD3^+、CD4^+、CD8^+及CD4^+/CD8^+)。结果:干预前,两组患者IL-2、IL-8及TNF-α无变化,差异无统计学意义(P>0.05);干预后,观察组患者的IL-2比对照组高,且对照组的IL-8及TNF-α比观察组的高,P<0.05,差异有统计学意义;干预前,两组患者的CD3^+、CD4^+、CD8^+及CD4^+/CD8^+与ET无变化;干预后,观察组的CD3^+、CD4^+、CD8+及CD4^+/CD8^+比对照组高,P <0.05,差异有统计学意义,且观察组的ET低于对照组且观察组总有效率明显高于对照组。结论:滋阴清热方治疗降低了血浆内皮素-1,减少炎症的出现,提高免疫功能。     

Loss of function,missense, and intronic variants in NOTCH1 confer different risks for left ventricular outflow tract obstructive heart defects in two European cohorts

Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes.     

脂蛋白相关磷脂酶A2、胰岛素样生长因子-1与老年VD患者认知功能的关系及预测价值研究

目的 探讨脂蛋白相关磷脂酶A2（Lp-PLA2）、胰岛素样生长因子-1（IGF-1）与老年血管性痴呆（VD）患者认知功能的关系及预测价值。方法 选择2019 年3～6 月在我院接受治疗的VD 患者60 例为研究对象，同时选取同期在我院接受检查的健康者60 例为对照组，比较两组患者的Lp-PLA2、IGF-1、简易智力状态检查量表评分（MMSE）水平；采用Pearson 相关性分析法对Lp-PLA2、IGF-1 与MMSE 评分的相关性进行分析；采用受试者工作曲线（ROC）下面积（AUC）比较Lp-PLA2、IGF-1 对VD 的预测价值。结果 观察组患者的Lp-PLA2 水平明显高于对照组（P＜0.05），观察组患者的IGF-1、MMSE 评分明显低于对照组（P＜0.05）；Lp-PLA2 与MMSE 评分呈负相关性，IGF-1 与MMSE 评分呈正相关性；Lp-PLA2 与IGF-1 诊断VD 的AUC 值分别为0.940、0.954。结论Lp-PLA2 水平越低，IGF-1 水平越高，患者的认知功能越好，且Lp-PLA2、IGF-1 对老年VD 患者均具有较高的预测价值。     

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。     

踇甲皮瓣联合腓动脉穿支皮瓣游离移植再造拇指并修复足部供区 15 例

目的总结应用踇甲皮瓣再造拇指及腓动脉穿支皮瓣游离移植修复足部供区的手术方法及临床效果。方法2016 年 6 月—2018 年 5 月，应用踇甲皮瓣联合腓动脉穿支皮瓣游离移植再造拇指并修复足部供区 15 例。男 10 例，女 5 例；年龄 21～48 岁，平均 34.6 岁。致伤原因：重物压砸伤 7 例，机器绞伤 5 例，电锯切割伤 3 例。Ⅰ度缺损 9 例，Ⅱ度缺损 6 例。入院至皮瓣手术时间 4～7 d，平均 5.2 d。结果术后踇甲皮瓣及腓动脉穿支皮瓣全部成活，切口均Ⅰ期愈合。患者均获随访，随访时间 8～24 个月，平均 16.4 个月。末次随访时，再造拇指指甲生长平整，有光泽，指腹饱满；足部皮瓣外形良好，颜色及质地接近受区。根据中华医学会手外科学会拇手指再造功能评定标准，获优 9 例、良 6 例；根据 Maryland 足功能评分标准，获优 10 例、良 5 例。患者行走步态正常，无跛行及疼痛不适。结论踇甲皮瓣修复拇指Ⅰ、Ⅱ度缺损，再造拇指可获得良好外观及功能；腓动脉穿支皮瓣具有血供可靠、血管恒定、易切取等优点，可有效修复足部供区。     

Endoplasmic reticulum stress is involved in ventilator-induced lung injury in mice via the IRE1α-TRAF2-NF-κB pathway

Inflammation plays a critical role in the development of ventilator-induced lung injury (VILI). Endoplasmic reticulum (ER) stress is associated with a variety of diseases through the modulation of inflammatory responses. However, little is known about how ER stress is implicated in VILI. In this study, murine mechanical ventilation models were constructed. Total protein and inflammatory cytokines were measured in bronchoalveolar lavage fluid (BALF), and lung tissue injury was assessed by histology. Our data revealed that mice subjected to high tidal ventilation (TV) for 4 h showed more severe pulmonary edema and inflammation than those of mice with spontaneous breathing and low TV-treatment. In addition, the high TV-treated animals upregulated the ER stress markers GRP78, CHOP, p-IRE1α, TRAF2, and p-NF-κB expression at both the mRNA and protein levels in lung tissue. Administration of thapsigargin exacerbated the histological changes, inflammation and expression of GRP78 and CHOP after high TV, but treatment with ER stress and IRE1α kinase inhibitors attenuated the pathological damage and downregulated the high expression of GRP78, CHOP, p-IRE1α, TRAF2, and p-NF-κB, suggesting that ER stress is involved in VILI though the IRE1α/TRAF2/NF-κB signaling pathway in mice.     

附加钢板技术治疗股骨干髓内钉术后骨不连的现状和研究进展

目的对附加钢板技术治疗股骨干髓内钉术后骨不连的历史、现状和进展进行综述。方法广泛查阅国内外关于附加钢板技术治疗股骨干髓内钉术后骨不连的临床研究文献，并进行综合分析。结果自 1997 年附加钢板技术已成功用于治疗股骨干髓内钉术后骨不连，根据原髓内钉是否失效，可分为保留原髓内钉和更换原髓内钉两类。该技术不仅适用于简单骨不连，还可用于合并严重畸形的复杂性骨不连。相比更换髓内钉、更换外侧钢板和双钢板技术，附加钢板技术手术创伤更小，骨折愈合时间更短，骨折愈合率更高，患者能更早重返社会和工作。然而，该技术也存在一些问题有待解决，包括双皮质螺钉固定困难、缺乏适合股骨干解剖型附加钢板以及缺乏术后功能和生活质量的评估研究。结论相比其他翻修固定方式，附加钢板技术能够获得更高的骨折愈合率和更好的临床预后。然而，术后患者能否在功能和生活质量方面进一步获益还有待证实。此外，还需要更高质量的临床对照研究深入证明其是否确实优于其他翻修固定方式。