表观遗传调控与青光眼发病机制研究进展

表观遗传学主要机制包括DNA甲基化、组蛋白修饰和miRNAs等。这些机制将环境与基因相联系，在基因的特异性表达过程中发挥重要作用，影响疾病的表型。青光眼是全球第一大不可逆致盲眼病，其发病机制复杂，受遗传和环境的共同影响。本文分别对DNA甲基化、组蛋白修饰和miRNAs参与青光眼发病的机制进行综述，以期为临床诊治提供参考。     

Ocular dysfunctions and toxicities induced by antiepileptic medications: Types,pathogenic mechanisms,and treatment strategies

Introduction: Ocular dysfunctions and toxicities induced by antiepileptic drugs (AEDs) are rarely reviewed and not frequently received attention by treating physicians compared to other adverse effects (e.g. endocrinologic, cognitive and metabolic). However, some are frequent and progressive even in therapeutic concentrations or result in permanent blindness. Although some adverse effects are non-specific, others are related to the specific pharmacodynamics of the drug.

Areas covered: This review was written after detailed search in PubMed, EMBASE, ISI web, SciELO, Scopus, and Cochrane Central Register databases (from 1970 to 2019). It summarized the reported ophthalmologic adverse effects of the currently available AEDs; their risks and possible pathogenic mechanisms. They include ocular motility dysfunctions, retinopathy, maculopathy, glaucoma, myopia, optic neuropathy, and impaired retinal vascular autoregulation. In general, ophthalmo-neuro- or retino-toxic adverse effects of AEDs are classified as type A (dose-dependent), type B (host-dependent or idiosyncratic) or type C which is due to the cumulative effect from long-term use.

Expert opinion: Ocular adverse effects of AEDs are rarely reviewed although some are frequent or may result in permanent blindness. Increasing knowledge of their incidence and improving understanding of their risks and pathogenic mechanisms are crucial for monitoring, prevention, and management of patients’ at risk.     

临床抗青光眼药物的新进展

青光眼是致盲的主要原因之一，构成视神经的神经节细胞轴突受到多种因素的损伤，其机制尚未完全明了。青光眼最重要的危险因素是眼压升高。由于青光眼的视神经损伤尚不能直接治疗，根据目前提供的唯一已知可治疗的危险因素，可以降低升高的眼压，而眼压与房水流出通道的功能息息相关。这些方面的药物均可以影响青光眼的进展。随着医疗技术的发展以及对青光眼发病机制认识的加深，新型抗青光眼药物也应运而生，为眼科医师提供新的选择。本文将对国内外新型抗青光眼药物从机制、药理特点及临床疗效等方面进行综述。     

前房注射卡波姆建立大鼠高眼压模型的观察

目的　前房注射卡波姆建立大鼠高眼压模型，观察卡波姆升眼压效果及对大鼠眼前节和视网膜的影响。方法　随机选取30只SD大鼠，注射前3 d早晚测量基线眼压。右眼定为实验眼，左眼定为对照眼，右眼放出房水后将30 μL的5 g·L^-1卡波姆混悬液注入前房，每日早10时、晚22时在大鼠清醒状态下测量眼压。每周进行双眼眼前节照相并对比。4周末处死26只大鼠（另4只持续观察眼压变化至注射后9周）并取双眼眼球行HE染色，观察实验眼与对照眼视网膜形态，对比视网膜厚度及房角形态。结果　注射前，实验眼白天和夜间眼压分别为（11.10±0.90）mmHg（1 kPa=7.5 mmHg）和（11.92±1.07）mmHg，对照眼分别为（11.22±1.07）mmHg和（11.76±1.08）mmHg；实验眼与对照眼相比，白天、夜间眼压差异均无统计学意义（均为 P＞0.05）；白天与夜间眼压相比，实验眼、对照眼差异均有统计学意义（均为P<0.05）。卡波姆在前房中呈现出弥散型和沉积型两种存在方式，弥散型和沉积型大鼠1周内眼压分别为（17.83±3.54）mmHg和（13.00±1.55）mmHg，两者相比差异具有统计学意义（P＜0.05）。注射后第1天至第19天，实验眼与对照眼白天眼压相比差异均具有统计学意义（均为P＜0.05）；注射后第1天至第27天，实验眼与对照眼夜间眼压相比差异均具有统计学意义（均为P＜0.05）。实验眼视网膜形态发生改变，注射后4周视网膜厚度为（254.70±21.80）μm，与对照眼的（346.73±24.63）μm相比，差异有统计学意义（P=0.00）。实验眼前房充满卡波姆及虹膜的混合成分，紧贴角膜内皮并延伸至房角，堵塞小梁网结构，正常虹膜形态消失；对照眼房角形态正常。结论　前房注射卡波姆建立大鼠高眼压模型，可维持高眼压4周以上，昼夜眼压差异较为明显，夜间眼压较白天更高，4周后视网膜出现高眼压损伤后的表现。     

Post-neoadjuvant strategies in breast cancer: From risk assessment to treatment escalation

The post-neoadjuvant setting in early breast cancer represents an attractive scenario for adjuvant clinical trials, offering the opportunity to test new drugs or combinations in high-risk patients who did not achieve pathologic complete response after primary treatment. No standard therapies are routinely proposed to patients with residual disease after neoadjuvant chemotherapy and few trials have explored this setting. To date, only one randomized phase III study showed the benefit of additional capecitabine after neoadjuvant chemotherapy, and international guidelines recommend at least to consider its use, particularly for triple negative breast cancer. Therefore, the management of these patients is still a clinical challenge, with limited data supporting the use of an additional adjuvant non-cross-resistant chemotherapy. Escalation strategies are currently under evaluation, with new agents proposed as supplementary post-neoadjuvant treatment (e.g. platinum salts, capecitabine, poly ADP-ribose polymerase inhibitors, immune checkpoint inhibitors, cyclin-dependent kinase 4/6 inhibitors). Based on these premises, selection criteria are critical to identify patients who may benefit from post-neoadjuvant therapies, through the validation of prognostic and predictive biomarkers for a reliable risk assessment and estimation of benefit.The present review summarizes the efforts in introducing new therapeutic options for patients with breast cancer and residual disease after neoadjuvant treatment, with a particular focus on the ongoing clinical trials and useful biomarkers for risk stratification.     

Effect of Tropicamide on Laser Flare Meter Measurements in Patients with Pseudoexfoliation

ABSTRACT

Purpose

To investigate the effect of 1% tropicamide on anterior chamber aqueous flare (ACAF) measurements acquired with laser flare meter in patients with pseudoexfoliation.     

Factors influencing development of residual stresses during crystallization firing in a novel lithium silicate glass-ceramic

ObjectiveDevelopment of residual stresses is a potential source of premature fractures in glassy materials, being of special interest in novel lithium silicate glass-ceramics that require a crystallization firing to achieve their final mechanical properties. The aim of this work was to assess the influence of various firing tray systems and the application of different cooling protocols on the development of residual stresses in Suprinity PC crowns. Their effect on the in vitro lifetime of the restorations was also studied.MethodsThirty crowns were milled out of Suprinity PC blocks and crystallized using one of five different commercial firing tray systems (n = 6). Samples in each group were cooled following a fast (FC = 5.5 °C/s), a slow (SC = 0.4 °C/s) or the manufacturer’s reference cooling (REF ). Obtained crowns were sagittally or transversally sectioned and the magnitude and distribution of residual stresses was determined using the light birefringence method. Extra crowns of three of the subgroups (n = 8) were produced and submitted to chewing simulation for 10⁶ cycles or until fracture ensued.ResultsAverage residual stresses ranged between 0 and 1.5 MPa (peaks of 5 MPa). Highest stress magnitudes were observed at the support areas of groups using firing pins, leading to thermal cracks in FC samples and premature failures in the REF subgroup. The use of fibrous pads and firing pastes limited the development of residual stresses, whereas application of SC regimes extended the lifetime of the restorations.SignificanceDevelopment of residual stresses during crystallization firing in lithium silicate glass-ceramics results critical for their mechanical performance and should be therefore avoided by ensuring a homogenous cooling of the structures.     

牙冠延长术在残根残冠修复中的临床疗效

目的评价牙冠延长术在牙体缺损达龈下的残根残冠修复中的临床疗效。方法自2004年5月至2005年6月,对32例患者的36颗牙体缺损达龈下的患牙,术前按断端位于龈下最深距离分为A组(20颗患牙,距离<3.0mm)和B组(16颗患牙,3.0mm≤距离≤4.0mm),均采用牙冠延长术暴露龈下牙体断面,术后6周行桩冠修复。分别记录和比较手术前、后牙周探诊深度(PD)、菌斑指数(PLI)、龈沟出血指数(SBI)和牙齿松动度,以观察临床疗效。结果术后随访患者6个月,两组病例术后6周牙体断端均暴露较好、龈缘颜色正常,术后修复效果有效率为100%,满意率为77.78%。A组术后无松动,修复效果满意;B组术后50.00%出现Ⅰ度松动,修复效果欠佳,两组修复效果比较差异有显著意义(P<0.05)。术后各阶段两组的PD、PLI、SBI均明显优于术前(P<0.05),但两组术后牙周指数比较差异无显著意义(P>0.05)。结论牙冠延长术有利于残根残冠的保存和修复,但要注意适应证的选择。     

NA:YAG激光虹膜切除术治疗闭角型青光眼201例临床观察

目的评价NA：YAG激光虹膜切除术治疗原发性闭角型青光眼和葡萄膜炎继发青光眼的临床疗效。方法回顾分析192例219眼原发性闭角型青光眼和9例葡萄膜炎继发青光眼，接受NA：YAG激光虹膜切除术后的临床效果，随诊16—46月。结果激光切孔一次成功205眼（占89e），激光能量在11—17．1mJ，67％病例在22—84Mj，击射次数2-33次。葡萄膜炎继发青光眼9眼均二次激光后虹膜孔通畅。95．61％术后眼压正常，视野无变化，术后早期一过性眼压升高占34％，术中出血占36％，房角色素增加占47％，1例术后28月接受小量切除术，8例术后需配合使用降眼压药物控制眼压。结论NA：YAG激光虹膜切除术是一种治疗闭角型青光眼的安全有效的方法。术前掌握适应症，把握手术时机，充分的术前准备是手术成功的关键。