INTRODUCTION

Pterygium is a common ocular surface disorder that is characterized by hypertrophy of the subconjunctival connective tissue and overlying epithelium. Chronic ultraviolet(UV) light exposure is a known cause of degenerative deposition of subepithelial collagen fibers, which eventually leads to pterygium development. Pterygium may only cause cosmetic complaints, severe subconjunctival hypertrophic scarring, and subsequent symblepharon, ocular motility restriction, and significant vision loss (Figure 1). These severe complications can impair quality of life and psychosocial function.

PROLIFERATIVE FEATURES OF PTERYGIUM

Pterygium has the propensity to grow and recurs frequently.Therefore, some have suggested that it is actually a tumorlike proliferative disorder, rather than a degenerative process.Pterygium does not have malignant features in that it does not spread to distant organs. However, several prior studies have described its other characteristics that mimic cancer,including unlimited growth and local tissue invasion.Microsatellite instability and loss of heterozygosity have been found to be clinically correlated with pterygia[1]. Thereafter,the development and growth of pterygium is significantly related to aberrancy of cell cycle progression, and ultimately uninhibited proliferation[2]. In addition, several studies have identified carcinoma in situ and dysplasia, and some have analyzed the expression of cell cycle/proliferation-related factors (e.g. p27, Ki-67, cyclin D1, p63, p16 and p53) in pterygium epithelium[3-5]. Based on these prior findings, it is conceivable that pterygium management should parallel that of cancer.

PREOPERATIVE EVALUATION TO PREDICT POSTSURGICAL RECURRENCE

The most significant concern for both patients with pterygium and surgeons is post-surgical recurrence. Unfortunately,the fibrovascular growth propensity of pterygium during recurrence is often more rapid and extensive than it is during its initial development. Therefore, it is difficult to establish a surgical strategy for recurrent cases. Recurrence and its severity vary depending on the preoperative conditions ofpterygium. Thus, to perform intervention with which less likely to cause postsurgical recurrence, especially in pterygium which is more likely to recur, is an essential prerequisite to a successful surgical outcome of pterygium. The excessive cautery of episcleral vessels or the improper use of mitomycin C (MMC) in pterygium treatment can cause devastating necrotizing scleritis. In contrast, the limited removal of pterygium tissue may lead to rapid recurrence. Therefore,there are two important main concepts in pterygium research:1) preoperatively identifying the risk factors for recurrence;2) selecting and devising a suitable intervention to prevent recurrence.

Figure 1 Severe cases of pterygium complicated by symblepharon,severe hypervascularization, motility restriction-related diplopia and impaired vision.

In a previous study, the flesh-like morphology of pterygium(grade T3) was well correlated with a higher recurrence rate after bare sclera surgery[6]. While searching for biomarkers that predict uninhibited proliferation, a recent study showed that the expression of stromal cell-derived factor 1 (SDF-1) in pterygium body fibroblasts increased the subsequent expression of transforming growth factor beta (TGF-β), a well-known pan-organic key fibrogenic stimulant[7]. It has also been reported that stromal fibroblasts from more severe pterygia (with thick body morphology) (grade T3 by Tan et al[6]) overexpressed angiogenin[8] and SDF-1[9] more than did the mild form of pterygia. The expression levels of both angiogenin and SDF-1 were positively correlated with that of alpha-smooth muscle actin, a marker of myofibroblast characteristics. Myo fibroblasts are the activated and transformed cells of fibroblasts. Myo fibroblasts are resistant to programmed cell death, and may perpetuate the synthesis of extracellular matrix for fibrotic tissue remodeling. In this study, we assumed there were diverse factors also associated with the propensity for post-surgical recurrence, including young age,current active growth, pre-existing disfiguration of lacrimal caruncle, ocular motility restriction; concurrent ocular surface inflammation, fibrogenic constitution (e.g. keloid tendency)and the genetic predisposition to recur (e.g. family history). At out institution, the variables are now used in the development of differential surgical strategies. Ideally, we expect that whole-genome sequencing may one day help to catalogue the characteristics and spectrum of germline alterations,enabling researchers to fully understand the genetic aspect of pterygium and its malignant mimicry. Similarly, there has been a recent effort to scan the proliferation-driving factor through microRNA arrays and to confirm such a regulator in pterygium fibroblasts[10].

深秋的傍晚寒意渐浓，李淑荣揉揉有些酸涩的眼睛。旁边桌上盒饭早已凉透，对甲方临时提出的要求进行反复分析、确认，让她顾不上休息吃饭。整理好厚厚的一摞资料，提起陪伴她多年的行李箱，李淑荣匆匆出门，她还要赶晚上7点的飞机，去成都进行汇报。

In conclusion, the most appropriate initial step in the management of pterygium is to determine the risk of recurrence using clinical information. Next, the pterygium tissue is removed with appropriate adjuvant options. In the future, it will be important to identify the molecular/genetic biomarkers of recurrence, as well as patient-individualized therapeutic methods in order to maximize therapeutic effectiveness overcoming the complicated problems in pterygia. Furthermore,the CRISPR-Cas9 system or “gene scissors”, declared the“Breakthrough of the Year 2015” by the journal Science, is cautiously predicted to be a therapeutic option in pterygium using gene-targeted fundamental techniques.

OPTIONS TO LOWER POST-SURGICAL RECURRENCES

The undisputed operative strategy to minimize the risk of pterygium recurrence is to maximize residual fibroblast ablation at the surgical wound area through thorough removal of subconjunctival fibrovascular tissue. There are several adjuvant options to reduce the proliferative activity of stromal fibroblasts during the postoperative recovery phase. These adjuvant therapies include: application of an antimetabolite such as MMC or 5-fluorouracil, intralesional steroid injection and insertion of multimicroporous expanded polytetra fluoroethylene (e-PTFE) in multirecurrent pterygia[11].In addition, the intraoperative uncovered wound area should be minimized using a conjunctival flap, amniotic membrane graft,or conjunctivo-limbal autograft to allow for rapid epithelial wound healing. The bare sclera technique, for example, has relatively high and variable recurrence rates from 33% to 88%[6]. A large open wound after pterygium excision inevitably results in severe pain. Based on our experience, severe pain induces exaggerated wound hypertrophy, leading to pterygium recurrence. This hypothesis is in line with our previous report,in which substance P, a neuropeptide famous for nociception,drove the mobilization of injury-inducible stromal-like cells from the bone marrow to participate in wound healing[12].Therefore, we do not support perioperative pain-provoking surgical methods such as bare sclera excision. In addition,delayed epithelial wound healing may induce alternative and prolonged stromal overgrowth, most likely due to a lack of contact inhibition with the overlying epithelial cells. In challenging cases of keloid constitution or repeated recurrence,we carefully avoid loss of the adjacent normal conjunctival epithelium. In addition, in these cases, we undoubtedly cover the large wound area by sliding or rotating the flap tissue of the nearby conjunctiva or conjunctivo-limbal allograft onto the base of the amniotic membrane graft. This process is followed by meticulous excision of the stromal pterygium tissue and gentle application of MMC with occasional temporary e-PTFE insertion.

施加腐殖质、零价铁和复合调理剂均明显降低了水稻各部位砷的含量。与对照相比，施加腐殖质、零价铁粉和复合调理剂后，早稻稻米中砷含量分别下降了29.6%，47.3%和53.8%；晚稻稻米中砷含量分别下降了 24.1%，27.8%和 60.2%，差异显著（P<0.01）。施加复合调理剂，晚稻稻米砷含量达到食品安全国家标准（GB 2762—2012）。

ACKNOWLEDGEMENTS

Conflicts of Interest: Kim KW, None; Kim JC, None.

阅读对孩子的影响太大了！最近这几年，我走访了全国各地约200所学校，其中大部分都是小学，从大都市的“重点小学”到乡镇小学，我都去做过关于阅读与写作的讲座。在讲座过程中，我总是有意识地频繁与孩子们互动，所以一场讲座做完，对于这个学校孩子的总体素质，我会有一个比较清晰的了解。

REFERENCES

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