解偶联蛋白1基因多态性与2型糖尿病心脑血管并发症的相关性

目的探讨解偶联蛋白1(UCP1)基因多态性与2型糖尿病(T2DM)心脑血管并发症的相关性。方法选取2019年7月—2020年7月住院治疗的T2DM 440例,根据有无心脑血管并发症分为观察组(T2DM合并心脑血管并发症)221例和对照组(单纯T2DM)219例。比较两组一般资料,UCP1在rs45539933、rs10011540及rs1800592位点的基因型分布与等位基因频率;通过多因素Logistic回归分析评估T2DM发生心脑血管事件的危险因素。结果观察组病程长于对照组,糖化血红蛋白水平高于对照组,而血清高密度脂蛋白胆固醇水平低于对照组(P<0.01)。观察组C/C基因型分布及C碱基频率均高于对照组(P<0.05)。C/C基因型是T2DM患者发生心脑血管并发症的危险因素(P<0.05)。结论UCP1基因多态性与T2DM心脑血管并发症的发生显著相关。     

超声引导下腰方肌阻滞联合丙泊酚麻醉在腹腔镜结直肠癌根治术中的应用

目的:研究超声引导下腰方肌阻滞联合丙泊酚麻醉在腹腔镜结直肠癌根治术中的应用价值。方法:选取90例择期进行腹腔镜结直肠癌根治术患者作为研究对象，随机分为观察组和对照组，各45例。对照组采用传统腰麻联合丙泊酚麻醉，观察组采用超声引导下腰方肌阻滞联合丙泊酚麻醉，比较两组患者术中（麻醉后5、15、30、60 min）收缩压（SBP）、舒张压（DBP）、心率（HR）和术后不同时间段的疼痛评分（VAS评分），以及加用镇痛药情况和肠道恢复排气时间和术后48 h内不良反应发生情况。结果:两组患者SBP、DBP、HR组间、不同时间点及交互差异均有统计学意义（P<0.05），且观察组麻醉后上述指标波动较对照组小（P<0.05）；麻醉前，两组患者皮质醇、肾上腺素水平无显著差异（P>0.05），麻醉后各时间点观察组患者上述指标水平均显著低于对照组（P<0.05）；两组患者VAS评分组间、不同时间点及交互差异均有统计学意义（P<0.05），且观察组术后各时间点VAS评分均显著低于对照组（P<0.05）；观察组不良反应发生率显著低于对照组（8.89% vs 24.44%, P<0.05）；观察组患者加用镇痛药的人数、剂量和肠道恢复排气时间均显著少于对照组（P<0.05）。结论:超声引导下腰方肌阻滞联合丙泊酚麻醉在腹腔镜结直肠癌手术中具有良好、稳定的麻醉效果，可有效缓解患者疼痛，减少术后不良反应发生。     

重复经颅磁刺激在孤独症谱系障碍中的应用进展

孤独症谱系障碍是一种患病率日益增长的神经发育综合征，可出现多种行为障碍。近年来，重复经颅磁刺激在孤独症谱系障碍治疗中取得了一些研究成果，但关于刺激参数选择、安全性及可行性评估方面仍存在一定争议。本文就其关于诱导长时程增强/抑制、调节皮质抑制的治疗机制、低频和高频经颅磁刺激的临床应用及目前涉及的安全性、道德伦理问题等局限性进行综述，从而为今后的研究与临床应用提供一定的参考依据。     

Structural insights into membrane remodeling by SNX1

The sorting nexin (SNX) family of proteins deform the membrane to generate transport carriers in endosomal pathways. Here, we elucidate how a prototypic member, SNX1, acts in this process. Performing cryoelectron microscopy, we find that SNX1 assembles into a protein lattice that consists of helical rows of SNX1 dimers wrapped around tubular membranes in a crosslinked fashion. We also visualize the details of this structure, which provides a molecular understanding of how various parts of SNX1 contribute to its ability to deform the membrane. Moreover, we have compared the SNX1 structure with a previously elucidated structure of an endosomal coat complex formed by retromer coupled to a SNX, which reveals how the molecular organization of the SNX in this coat complex is affected by retromer. The comparison also suggests insight into intermediary stages of assembly that results in the formation of the retromer-SNX coat complex on the membrane.

Sorting nexins (SNXs) exist as a large family of proteins defined by the presence of a PX (phox homology) domain (1, 2). Members of this family have been found to act as coat proteins in endosomal pathways that include recycling from endosomes to the plasma membrane and retrieval from endosomes to the Golgi complex (3, 4). Defects in these transport processes is associated with various neurologic disorders including Alzheimer’s disease, Parkinson’s disease, and Down’s syndrome (5, 6).Coat proteins assemble into complexes on the membrane to initiate intracellular transport pathways by coupling two main functions: bending the membrane to generate transport carriers and binding to cargoes for their sorting into these carriers (7). Retromer, a trimeric complex consisting of Vps26, Vps29, and Vps35, has been found to couple with different SNXs to form multiple endosomal coat complexes, in which select members of the SNX family act in membrane deformation while retromer acts in cargo recognition (8–17). Recently, a detailed molecular view of this functional cooperation has been achieved by elucidating the structure of a retromer-SNX complex on the membrane (18).Notably, it has been further discovered recently that an endosomal coat complex can be formed with only SNX members. SNX1/2 have been found to heterodimerize with SNX5/6 to form the endosomal SNX–BAR sorting complex for promoting exit 1 (ESCPE-1) complex, in which SNX1/2 are proposed to act in membrane deformation while SNX5/6 act in cargo recognition (19). As such, a key question has become whether SNX that acts in membrane deformation in this type of coat complex would be organized similarly on the membrane, as previously elucidated for SNX in the context of a retromer-SNX complex (18).One of the best characterized mechanisms of membrane deformation involves proteins that possess the BAR (Bin/Amphiphysin/Rvs) domain. This domain has been shown to undergo homodimerization to form a banana-shaped structure, which can impart membrane curvature through a scaffolding mechanism that involves electrostatic interactions between the positive charges lining the concave side of the curved BAR dimer and the negative charges that line the surface of the membrane bilayer. In some cases, the BAR domain can deform the membrane through a second mechanism, which involves the formation of an amphipathic helix that inserts into one leaflet of the membrane bilayer to generate bilayer asymmetry in driving membrane curvature (20, 21).Besides the PX domain, SNX1 also possesses a BAR domain. However, studies have found that its BAR domain is not sufficient in driving membrane deformation. Instead, the PX domain as well as the linker region between the BAR and PX domains are also needed (22, 23). As such, a key goal has been to achieve a better understanding of how the various parts of SNX1 contribute to its ability to deform the membrane.Structural studies, such as those involving crystallography and single-particle electron microscopy (EM), have been advancing a molecular understanding of coat proteins (24), including components of endosomal coats (17, 19, 22, 25–27). Notably, however, these approaches solve protein structures in solution, but the functional form of coat proteins involves their association with the membrane. In this study, we have pursued cryo-EM to reveal how SNX1 is organized on the membrane to explain its ability to deform the membrane. The result advances a molecular understanding of how an endosomal coat that contains only SNXs generates transport carriers. Moreover, by comparing our SNX1 structure to the previously solved retromer-SNX structure (18), we delineate the extent to which the molecular organization of SNX on the membrane is affected by the presence of retromer. This comparison also suggests insight into intermediary stages of coat assembly that form the retromer-SNX complex on the membrane.