Retinoic Acid-related Orphan Receptor-α Is Induced in the Setting of DNA Damage and Promotes Pulmonary Emphysema

Rationale: The discovery that retinoic acid-related orphan receptor (Rora)-α is highly expressed in lungs of patients with COPD led us to hypothesize that Rora may contribute to the pathogenesis of emphysema. Objectives: To determine the role of Rora in smoke-induced emphysema. Methods: Cigarette smoke extract in vitro and elastase or cigarette smoke exposure in vivo were used to model smoke-related cell stress and airspace enlargement. Lung tissue from patients undergoing lung transplantation was examined for markers of DNA damage and Rora expression. Measurements and Main Results: Rora expression was induced by cigarette smoke in mice and in cell culture. Gene expression profiling of Rora-null mice exposed to cigarette smoke demonstrated enrichment for genes involved in DNA repair. Rora expression increased and Rora translocated to the nucleus after DNA damage. Inhibition of ataxia telangiectasia mutated decreased the induction of Rora. Gene silencing of Rora attenuated apoptotic cell death in response to cigarette smoke extract, whereas overexpression of Rora enhanced apoptosis. Rora-deficient mice were protected from elastase and cigarette smoke induced airspace enlargement. Finally, lungs of patients with COPD showed evidence of increased DNA damage even in the absence of active smoking. Conclusions: Taken together, these findings suggest that DNA damage may contribute to the pathogenesis of emphysema, and that Rora has a previously unrecognized role in cellular responses to genotoxicity. These findings provide a potential link between emphysema and features of premature ageing, including enhanced susceptibility to lung cancer.     

Mimotopes selected by biopanning with high-titer HIV-neutralizing antibodies in plasma from Chinese slow progressors

ObjectiveOne approach to identifying HIV-1 vaccine candidates is to dissect the natural antiviral immune response in treatment-naïve individuals infected for over ten years, considered slow progressor patients (SPs). It is suspected that SP plasma has strongly neutralizing antibodies (NAb) targeting specific HIV viral epitopes.MethodsNAbs levels of 11 HIV-1-infected SPs were detected by PBMC-based neutralization assays. To investigate SP NAb epitope, this study used a biopanning approach to obtain mimotopes of HIV-1 that were recognized by SP plasma NAbs. IgG was purified from high-titer NAb SP plasma, and used as the ligand for three rounds of biopanning to select HIV-specific mimotopes from a phage-displayed random peptide library. Double-antibody sandwich ELISA, competitive inhibition assays, and peptide sequence analysis were used to evaluate the characteristics of phage-borne mimotopes.ResultsSPs had significantly more plasma neutralizing activity than typical progressors (TPs) (p = 0.04). P2 and P9 plasma, which have highest-titer HIV-NAb, were selected as ligands for biopanning. After three rounds of biopanning, 48 phage clones were obtained, of which 22 clones were consistent with requirement, binding with HIV-1 positive plasma and unbinding with HIV-1 negative plasma. Compared with linear HIV-1 protein sequence and HIV-1 protein structure files, only 12 clones were possible linear mimotopes of NAbs. In addition, the C40 clone located in gp41 CHR was found to be a neutralizing epitope, which could inhibit pooled HIV-1 positive plasma reaction.ConclusionBiopanning of serum IgG can yield mimotopes of HIV-1-related antigen epitopes. This methodology provides a basis for exploration into HIV-1-related antigen-antibody interactions and furthers NAb immunotherapy and vaccine design.     

高度近视合并脉络膜脱离型视网膜脱离预后相关因素分析

目的 分析高度近视合并脉络膜脱离型孔源性视网膜脱离（RRD-CD） 患者的预后相关因素。设计 回顾性病例系列。研究对象 2004-2018年北京同仁医院高度近视合并RRD-CD患者占836例。方法 回顾北京同仁医院住院HIS系统,收集高度近视合并RRD-CD手术治疗患者临床资料。随访6个月视网膜复位为复位组,发生视网膜再脱离为未复位组。采用Logistic回归法分析视网膜脱离复发的危险因素。主要指标 手术成功率及复发危险因素。结果 共纳入高度近视合并RRD-CD患者836例,平均年龄（56.51±12.14）岁;男性518例（61.9%）,右眼发病434例 （51.9%）。视网膜脱离未复位为22.7%,与视网膜复位患者相比,未复位患者年龄较轻,术前视力、眼轴、晶状体状态、视网膜裂孔、增生性玻璃体视网膜病变（PVR）等级及手术方式等差异均有统计学意义,其中年龄〔优势比（OR）=0.972,95%可信区间（95%CI）,0.967~0.989〕,术前视力光感（OR=1.898,95%CI为1.297~2.777）,人工晶状体眼（OR=1.860,95%CI为1.255~2.758）,眼轴>30 mm（OR=1.718,95%CI为1.240~2.379）,巨大视网膜裂孔（OR=2.464,95%CI为1.495~4.063）及PVR D级（OR=1.551,95%CI为1.046~2.300）为视网膜脱离未复位的危险因素。结论 高度近视合并RRD-CD患者男性比例大,中年发病、超高度近视、人工晶状体眼、巨大视网膜裂孔及PVD D级患者首次手术成功率低,视网膜脱离易复发。（眼科,2021,30： 42-46）     

年龄相关性白内障患者14万例角膜前表面散光的分布特征

目的分析中国18家医院的14万例年龄相关性白内障患者角膜前表面散光的分布特征。方法回顾性系列病例研究。连续性收集2015年7月至2018年10月于中国18家爱尔眼科医院就诊的40岁以上年龄相关性白内障患者143889例(143889只右眼)的眼部生物学参数资料。角膜前表面散光度数和轴向、前房深度、角膜屈光力、眼轴长度等眼球参数采用IOLMaster 500测量,获取3次测量结果的平均值。各医院将资料整理分析后提交给武汉爱尔眼科医院进行总体分析。非正态分布数据以M(P25~P75)表示;采用Mann-Whitney检验、Kruskal-Wallis检验、χ²检验等分析角膜前表面散光度数和轴向在不同性别、年龄、前房深度、角膜屈光力、眼轴长度中的分布差异。结果143889例患者中女性84319例,男性59570例;年龄为72(65~78)岁;角膜散光度数为0.84(0.51~1.33)D,散光度数≥0.75 D者80895例(56.22%),散光度数≥1.00 D者57304例(39.83%)。女性角膜散光度数为0.87(0.53~1.37)D,男性为0.82(0.50~1.29)D(U=-14.891);女性顺规散光比例为33.26%(28046/84319),逆规散光比例为49.08%(41385/84319);男性顺规散光比例为34.26%(20408/59570),逆规散光比例为46.91%(27945/59570)(χ²=70.913),差异均有统计学意义(均P<0.05)。随年龄增加,角膜散光度数先由0.94(0.57~1.48)D减少至0.75(0.46~1.18)D,后又增大至1.19(0.74~1.79)D,差异有统计学意义(H=1263.438,P<0.05),变化的转折在61~70岁。随着年龄的增大,顺规散光比例减小[由77.50%(396/511)减少至12.50%(3/24)],逆规散光比例增大[由11.15%(57/511)增大至79.07%(34/43)],斜向散光比例变化不大[17.02%(16/94)至19.92%(245/1230)],分布差异有统计学意义(χ²=10174.496,P<0.05)。前房越浅,角膜散光度数越大,由0.82(0.51~1.31)D增大至1.05(0.61~1.56)D;逆规散光比例越大,由47.32%(60207/127227)增大至51.69%(184/356),差异均有统计学意义(H=409.961,χ2=120.995;均P<0.05)。平均角膜屈光力越大,角膜散光度数越大,由0.80(0.49~1.33)D增大至0.95(0.58~1.53)D;逆规散光比例越小,由52.84%(4963/9392)减小至39.97%(9023/22577),差异均有统计学意义(H=808.562,χ²=752.147;均P<0.05)。不同眼轴长度相比,当眼轴长度>25.00 mm时,角膜散光度数最大,为1.04(0.62~1.65)D;逆规散光比例最大,为49.00%(10964/22376),差异均有统计学意义(H=2071.198,χ²=131.130;均P<0.05)。结论年龄相关性白内障患者角膜前表面散光轴向以逆规散光为主。随着年龄的增大,角膜散光度数有先减小后增加的趋势。65岁为顺规散光向逆规散光变化的转折点。前房越浅,角膜前表面散光度数以及逆规散光比例越大。当眼轴长度>25.00 mm时,角膜前表面散光度数和逆规散光比例最大。     

FS-LASIK与FS-LASIK联合快速角膜胶原交联术矫正高度近视术后早期屈光度及角膜高阶像差比较

目的：比较飞秒激光辅助的准分子激光原位角膜磨镶术(FS-LASIK)与FS-LASIK联合快速角膜胶原交联术(FS-LASIK Xtra)矫正高度近视术后早期屈光度及角膜高阶像差变化特点,评估两种术式矫正高度近视的早期效果。

方法：回顾性病例对照研究。纳入2019-04/2020-04在我院进行FS-LASIK Xtra及FS-LASIK的高度近视患者42例84眼,每组各21例42眼,术后随访3mo,比较两组患者术后裸眼视力(UCVA)、等效球镜(SE)、散光度及角膜高阶像差。

结果：FS-LASIK Xtra组患者术后1d UCVA(LogMAR)低于FS-LASIK组(P<0.01),其余时间点两组间比较均无差异(P>0.05)。两组患者术后SE均较术前明显降低,术后3mo,FS-LASIK Xtra组有38眼(90%)、FS-LASIK组有41眼(98%)术眼SE在±1.00D以内。两组患者术后均有35眼(83%)的术眼残余散光在0.50D以内。两组术后3mo角膜总高阶像差、球差、彗差及三叶草差均较术前增大,FS-LASIK Xtra组总高阶像差及三叶草差大于FS-LASIK组(均P<0.05)。

结论：FS-LASIK与FS-LASIK Xtra矫正高度近视在术后早期均具有较好的有效性和可预测性,术后早期角膜总高阶像差均增加,且行FS-LASIK Xtra增加更显著。     

Rectangular 3-snip punctoplasty versus punch punctoplasty with silicone intubation for acquired external punctal stenosis: a prospective randomized comparative study

Xuan Liao. Department of Ophthalmology, Affiliated Hospital of North Sichuan Medical College, 1 Mao Yuan Nan Road, Nanchong 637000, Sichuan, China. aleexand@163.com