慢性移植物抗宿主病(chronic graft-versus-host disease,cGVHD)是骨髓移植后最具有破坏性并发症之一。移植物抗宿主病(graft-versus-host disease,GVHD)发生在10%~80%的造血干细胞移植(hematopoietic stem cell transplantation,HSCT)受者中,而眼睛是人身体最脆弱的器官之一,有40%~60%接受HSCT的患者发生眼部GVHD,它主要影响泪腺、睑板腺、角膜和结膜等。cGVHD相关性干眼(dry eye associated with chronic graft-versus-host disease,cGVHD-DE)是眼部GVHD最多见的表现形式。cGVHD-DE的长期治疗因涉及多学科、多重结合治疗,至今仍然具有挑战性,其除了全身免疫抑制和眼部润滑剂外,通常还使用局部类固醇、环孢霉素和他克莫司滴眼液。针对中度和重度cGVHD-DE的治疗干预包括使用自体血清滴眼液和佩戴巩膜镜等,新兴起的治疗方案包括重链透明质酸 (heavy chain-hvaluronan,HC-HA)/穿透素(pentraxin 3,PTX3)结膜下注射、间充质基质细胞静脉注射、抑制纤维化药物等。
Chronic graft-versus-host disease (cGVHD) is one of the most devastating complications following bone marrow transplantation. GVHD develops in 10–80% of patients after hematopoietic stem cell transplantation (HSCT). The eye is one of the most vulnerable organs of the human body. Ocular GVHD occurs in 40–60% of patients with GVHD undergoing HSCT, and it mostly affects the lacrimal glands, meibomian glands, cornea, and conjunctiva. The most common form of ocular GVHD is dry eye disease (DED). The long-term treatment of cGVHD-related dry eye syndrome remains challenging and involves a multidisciplinary approach. Besides systemic immunosuppression and ocular lubricants, topical steroids, topical cyclosporine, and topical tacrolimus are commonly prescribed. Newer therapeutic interventions for moderate and severe cGVHD-related DED include using serum eye drops and scleral contact lenses. Emerging treatment options include subconjunctival injection of heavy chain-hyaluronan (HC-HA)/ pentraxin 3 (PTX3), intravenous injection of mesenchymal stromal cells, antifibrotic drugs, etc. This article reviews the mechanisms, clinical findings, and treatment of cGVHD-related dry eye syndrome.
目的:探讨2型糖尿病(type 2 diabetes mellitus,T2DM)患者二甲双胍治疗与糖尿病性视网膜病变(diabetic retinopathy,DR)的相关性。方法:回顾2015年9月至2020年8月在中日友好医院眼科就诊的1 891例T2DM患者的临床资料,对病程≥10年的324例T2DM患者的一般资料、内科疾病史、糖尿病治疗史、眼科检查和实验室血生化指标进行回顾性病例研究。根据是否接受二甲双胍治疗分为二甲双胍治疗组与非二甲双胍治疗组,根据眼底检查结果同时结合DR临床诊断标准,将DR分为无明显DR、非增生性DR及增生性DR。采用logistic多因素回归分析判断年龄、性别、糖尿病发病年龄、糖尿病病程、高血压病程、高血脂病程、吸烟年数、体重指数、胰岛素治疗及空腹血糖、糖化血红蛋白、总胆固醇、三酰甘油、尿酸和血肌酐水平对结局变量的影响。结果:在DR的发病风险方面,二甲双胍治疗组与非二甲双胍治疗组的差异无统计学意义(P>0.05)。对T2DM患者DR发生及不同分期的相关变量行单因素及多因素分析,结果显示吸烟年数、空腹血糖及肌酐均与DR发病呈正相关(均P<0.05),而年龄与DR发病呈负相关(P<0.01),糖尿病发病年龄与DR发生呈显著负相关(OR=0.95,95%CI:0.92~0.98,P=0.0003)。在二甲双胍治疗的T2DM患者中,二甲双胍的疗程(OR=1.02,95%CI:0.96~1.08,P>0.05)及平均剂量(OR=1.50,95%CI:0.79~2.84,P>0.05)与DR的发生与进展均无显著相关性;女性DR发生与进展的风险较男性低(P<0.05);合并胰岛素治疗与DR发生呈明显正相关(OR=3.11,95%CI:1.59~6.07,P<0.01);吸烟年数长、糖化血红蛋白及尿酸水平高于正常范围均与DR的发生与进展呈正相关(P<0.05)。在口服二甲双胍患者中,未使用胰岛素治疗组和联合使用胰岛素组的DR发病风险有显著差异(P<0.01);而未口服二甲双胍患者中,胰岛素治疗与DR发生呈正相关(OR=12.43,95%CI:3.75~41.19,P<0.0001)。结论:病程10年以上T2DM患者中,二甲双胍治疗与DR发生与进展均无显著相关性。
Objective: To investigate the correlation between metformin therapy and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods: The clinical data of 1 891 patients with type 2 diabetes mellitus attending the ophthalmology department of China-Japan Friendship Hospital from September 2015 to August 2020 were reviewed. A retrospective study was performed on 324 cases of these T2DM patients with disease duration ≥10 years. Medical records of all patients including general information, history of medical disease, diabetes treatment, ophthalmologic examination and blood biochemical indices were collected. According to whether metformin treatment was received or not, the patients were divided into a metformin-treated and a non-metformin-treated groups. DR is classified into non-obvious DR, non-proliferative DR and proliferative DR according to the fundus examination and the clinical diagnostic criteria of DR. Logistic multiple regression analysis was used to determine the effects of age, sex, age of DM onset, duration of DM, duration of hypertension,duration of hyperlipidemia, years of smoking, body mass index, insulin treatment and fasting glucose, glycated hemoglobin, total cholesterol, triglycerides, uric acid and blood creatinine levels on DR. Results: There was no statistically significant difference in the risk of developing DR between the metformin-treated and non-metformin-treated groups (P>0.05). Univariate and multifactorial analyses of variables related to the occurrence and different stages of DR in patients with T2DM showed that years of smoking, fasting glucose and creatinine were positively associated with DR (P<0.05), while age was negatively associated with DR (P<0.01), and age of DM onset was significantly negatively associated with DR (OR=0.95, 95%CI: 0.92 to 0.98, P=0.0003). In T2DM patients treated with metformin, neither the duration of metformin (OR=1.02, 95%CI: 0.96 to 1.08, P>0.05) nor the mean dose(OR=1.50, 95%CI: 0.79 to 2.84, P>0.05) was significantly associated with developing DR. The risk of developing DR was lower in women than in men (P<0.05); combined insulin therapy was significantly positively correlated with the risk of DR (OR=3.11, 95%CI: 1.59 to 6.07, P<0.01); long-term smoking, glycosylated hemoglobin and uric acid levels higher than normal were positively associated with DR (P<0.05). In metformin users, there was a significant difference in the risk of developing DR between the no-insulin treatment group and the combined insulin group (P<0.01); and among patients not using metformin, insulin therapy was positively associated with the occurrence of DR (OR=12.43, 95%CI: 3.75 to 41.19, P<0.0001). Conclusion: There was no significant association between metformin treatment and DR among patients with T2DM for >10 years.
目的:建立高效液相色谱法(high-performance liquid chromatography,HPLC)测定盐酸丁卡因滴眼液中盐酸丁卡因和羟苯乙酯的含量。方法:采用Agilent Eclipse PLUS C18色谱柱(250 mm ×4.6 mm,5 μm);以1%三乙胺溶液(三乙胺10 mL,加水990 mL,用冰醋酸调节pH值至5.0±0.5)-乙腈(65 : 35)为流动相,流速为1.0 mL/min;柱温为30 ℃;检测波长为256 nm;进样体积20 μL。结果:盐酸丁卡因在0.05~0.36 mg/mL范围内线性关系良好( r =1.000),平均回收率为99.2%,相对标准偏差(relative standard deviation,RSD)为0.3%(n=9),羟苯乙酯在3.02~24.14 μg/mL范围内线性关系良好(r=1.000),平均回收率为98.2%,RSD为0.4%(n=9),该方法重现性好。对照品溶液和供试品溶液在室温放置24 h基本稳定;结论:本方法简便、快速、准确。适用于检测盐酸丁卡因滴眼液中盐酸丁卡因和羟苯乙酯的含量。
Objective: To establish a high-performance liquid chromatography (HPLC) method for the determination of tetracaine hydrochloride and ethyl hydrobenzoate in tetracaine hydrochloride eye drops. Methods: The analytic column was Agilent Eclipse Plus C18 (4.6 mm ×250 mm, 5 μm) and the mobile phase was 1% triethylamine solution (10 mL triethylamine and 990 mL water, pH adjusted to 5.0±0.5 with glacial acetic acid) - acetonitrile (65:35) at a flow rate of 1.0 mL/min. The detection wavelength was 256 nm and the column temperature was 30 ℃. The injection volume was 20 μL. Results: The linear range of tetracaine hydrochloride was well shown within 0.05–0.36 mg/mL (r=1.000). The average recovery rate of tetracaine hydrochloride was 99.2% with relative standard deviation (RSD) 0.3% (n=9). The linear range of ethyl hydrobenzoate was well shown within 3.02–24.14 μg/mL (r=1.000). The average recovery rate of tetracaine hydrochloride was 98.2% with RSD 0.4%(n=9). The method had high reproducibility. The reference solution and testing solution were stable for 24 h in room. Conclusion: The method is simple, quick and accurate, which is suitable for the determination of tetracaine hydrochloride and ethyl hydrobenzoate in tetracaine hydrochloride eye drops.
内源性干细胞在组织的损伤修复过程中组织相容性好、致瘤风险低,相较于外源性干细胞具有不需要体外扩增和培养、疾病传播风险低的优点,在细胞治疗领域具有显著优势。现在已经有多种使用内源性干细胞进行疾病治疗的成熟方式,应用领域包括了全身各种器质性和功能性疾病。在眼组织中,晶状体具有终生生长的能力且便于观察,是实现再生修复的突破点。哺乳动物中晶状体再生的实现有赖于晶状体内源性干细胞的定位和改良手术方式,以保留晶状体干细胞,并创造适合晶状体再生的微环境。对再生后的晶状体蛋白质组成分析,发现其类似成熟晶状体,而非胚胎期的晶状体,提示晶状体再生的调控与胚胎期的诱导发生并不相同;而调控晶状体再生的策略不仅着眼于干细胞的激活和正确分化的诱导,对其上皮间质转化过程也需要进行调控。在未来,为将晶状体再生的经验应用于其他眼组织中,动员内源性干细胞并促进其生长,可以添加细胞有效成分,比如外泌体、线粒体、小分子化合物等,模拟细胞应激;此外,还可以通过手术或生物材料辅助,恢复晶状体结构和环境。
Endogenous stem cells have significant advantages in cell therapy for excellent histocompatibility, low tumorigenicity risk, unnecessity for in vitro expansion and culture, and low disease transmission risk. There have been some applications for endogenous stem cells in treating diseases, targeting some organic and functional diseases throughout the body. In ocular tissue, the lens is a breakthrough for regenerative therapy due to its potential to grow throughout life and observation accessibility. Achieving lens regeneration in adult mammals attributes to some prerequisites. Firstly, the location of endogenous stem cells in the lens has been identified. Then, surgical approaches have been advanced to preserve lens stem cells and create a microenvironment suitable for lens regeneration. Protein compositional analysis of the regenerated lens reveals that it is similar to a mature lens rather than an embryonic lens, suggesting that the regulation of lens regeneration is not the same as the induction of embryonic onset. The strategy for regulating lens regeneration needs to focus not only on the activation and proper differentiation of stem cells but also on regulating the process of epithelial mesenchymal transition (EMT). In the future, in order to apply the experiences of lens regeneration to other ocular tissues, to mobilize endogenous cells and promote their growth, some strategies could be used. These strategies include mimicking cellular stress via the addition of cellular active ingredients, such as exosome, mitochondria, and small molecular compounds. Additionally, we can also try to restore lens tissue structure and microenvironment through surgical or biomaterial assistance.
目的:探讨基于微信的图像存储和传输系统(picture archiving and communication system,PACS)教学在眼眶科规培医生中的教学效果及质量评价。方法:将中山眼科中心眼眶科轮训的66名规培医生分为A组(PACS组)与B组(微信+PACS组)。通过出科考核和问卷分析比较两组学生的教学效果及满意度。结果:B组学生的基础知识测试和阅片技能测试得分均显著高于A组(P<0.001,P=0.037)。教学效果自我评估量表显示B组学生对解剖结构位置的熟悉程度、影像学诊断、鉴别诊断能力、工作中解读CT或MRI图像的能力预判,以及对CT或MRI影像学的兴趣,明显优于A组(均P<0.001)。所有学生(100.00%)对这种教学模式感到非常满意。结论:在眼眶科住院医师规划化培训中应用基于微信的PACS教学模式能显著提高教学效果和满意度,提高教学质量。
Objective: To evaluate the application quality of picture archiving and communication system (PACS) based on WeChat in standardized resident training in orbital department. Methods: A total of 66 doctors trained in the Orbital Department of Zhongshan Ophthalmic Center were divided into group A (PACS group) and Group B (WeChat +PACS group). The quality and feedback of teaching of the two groups of students were compared through examination and questionnaire. Results: The scores of basic knowledges and reading skills of group B were significantly higher than those of group A (P<0.001, P=0.037). The self-assessment scale for teaching quality showed that the students in group B were superior to group A in understanding the position of anatomical structure, imaging diagnosis and differential diagnosis according to CT or MRI, interpreting CT or MRI images in the future, and interest in CT or MRI imaging (all P<0.001). All the students (100.00%) were very satisfied with this mode of teaching. Conclusion: The application of PACS based on WeChat in standardized resident training in orbital department can significantly improve the quality and satisfaction of ophthalmology teaching.
在晶状体纤维细胞分化的终末阶段,细胞核、线粒体、内质网及高尔基体等膜性细胞器会发生程序性的降解,这对晶状体透明性的维持至关重要。然而,晶状体细胞器降解过程的机制尚不明确。研究晶状体细胞器的降解过程可为阐明白内障的发病机制提供理论依据,也有望为晶状体再生提供新的干预靶点。本文就晶状体细胞器降解过程及其机制进行综述。
During terminal differentiation of lens fiber cells, nuclei and other organelles experience programmed elimination.This process is essential for the maintenance of lens transparency. However, the mechanisms underlying lens organelle degradation remain unclear. Identification of the mechanisms can provide a theoretical basis for elucidating the pathogenesis of cataract and is expected to reveal new intervention targets for lens regeneration. In this review, we discuss potential mechanisms and the process of lens organelle degradation.
目的:观察生物工程角膜应用于感染性角膜炎的治疗效果。方法:对成都爱迪眼科医院19例采用生物工程角膜治疗的感染性角膜病角膜植片存活状况、术后视力变化及并发症进行回顾性分析。与同期22例人来源供体角膜移植行术后排异对比。结果:在19例患者中,女9例(47.37%),平均年龄53.32岁;病因中细菌性角膜炎7例(36.84%),真菌性角膜炎8例(42.11%),病毒性角膜炎4例(21.05%)。术前裸眼视力检查:光感3例(光定位准),手动5例,眼前指数4例,3.0~3.9者7例。随访1~14个月未发生原发感染复发;植片成活18例(94.74%),1例1月内植片溶解再手术(5.26%)。裸眼视力4.0~4.5者15例(78.95%),3.0~4.0者3例(15.79%),数指1例(5.26%)。远期(6~12个月以上)生物工程角膜移植术后角膜缘新生血管更易侵入,以植片缘环形浑浊为主。两组间排异差异无统计学意义(Mann-Whitney检验,P=0.736)。结论:生物工程角膜具有较好的人角膜结构替代功能,对未累及全层的感染性角膜疾病起到较好的结构和功能重建作用,恢复有用视力,缓解角膜供体来源不足,有一定推广意义。
Objective: To observe the outcomes of bioengineered cornea for lamellar keratoplasty in the infectious keratitis.Methods: A total of 19 cases with infectious keratitis treated by bioengineered cornea in Chengdu Aidi Eye Hospital were analyzed retrospectively. The results of graft survival, visual acuity and complications were collected.Rejection reaction was compared with 22 cases of human donor corneal lamellar keratoplasty during the same period. Results: In the 19 cases patients, 9 cases were women (47.37%) with the average age of 53.32 years. Among the pathogenic factors, 7 cases were bacterial keratitis (36.84%), 8 cases were fungal keratitis (42.11%) and 4 cases were viral (21.05%). The results of preoperative uncorrected visual acuity (UCVA) showed that 3 cases were light perception (accurate light positioning), 5 cases were hand moving, 4 cases were counting finger, and 7 cases were in the range of 3.0–3.9. In the follow-up, no case of primary infection recurrence occurred; 18 grafts survived except one case dissolved end with re-transplant by human donor. The postoperative UCVA of 15 cases (78.95%) were in the range of 4.0–4.5, 3 cases were in the range of 3.0–4.0 (15.79%), and 1 case of counting finger (5.26%). There was no significant difference in rejection action (P=0.736). In the follow-up more than 6–12 months, the limbal neovascularization of the biological engineering cornea is more likely to invade with the result of ring shape opacity at the graft edge. Conclusion: The biological engineering cornea can play a good role in the reconstruction for the cases with infectious keratitis. It provides another way to solve the shortage of corneal grafts.
研究生导师的能力和水平是影响研究生教育质量的最关键因素之一。针对眼科学研究生专业基础 知识薄弱、动手实践机会缺乏、创新能力不足,导师队伍教学主动性不强、活力欠佳等问题,中 山眼科中心逐步建立了“行政+专家”的双重教学管理架构,引导激励教师积极主动参与、推动研 究生课程改革、科研创新能力培训、教学信息化建设、教学质控与学生管理等各项教学改革与决 策,通过不断完善教师参与教学改革共同治理的长效机制,打造高素质的教师队伍,实现高质量 的眼科学研究生培养。
The ability and level of postgraduate tutor is one of the key factors affecting the quality of graduate education. In view of the weak basic ophthalmic knowledge, lack of practical opportunities and the inefficiency in innovation ability among ophthalmology graduates, as well as the lack of initiative and vitality in teaching team, Zhongshan Ophthalmic Center, Sun Yat-Sen University has been gradually established the dual management structure of “administration and experts”. By guiding and encouraging the teachers participate in the curriculum reform of graduates, scientific research ability training, management informatization, the teaching quality control, student administration and so on. Through improving the long-term mechanism of teachers’ participation in teaching reform governance, the quality of teachers has been improved, which promote the high-quality development of ophthalmology graduate education.
住院医师规范化培训(简称“住培”)是我国新医改的一项重要举措,旨在通过住培来使我国临床 整体医疗水平同质化提高,解决民众日益增长的医疗需求和各地医疗发展不平衡之间的矛盾。我 国眼科住培改革经历十余年,在追求同质化的实践中发现一些值得重视的问题,如教学师资的选 拔和培训、临床操作类教学的落实、教学师资待遇的提升以及包括人文在内的住院医师诊疗能力 全面培养等。本文探讨了这些问题的根源和解决方法,希望通过改革将住培这一临床医学基础工 程更好的落到实处。
Standardized resident training (called ‘ZhuPei’ for short in Chinese) is an important measure of the New Healthcare Reform in China, aiming to promote the homogenization of clinical medicine level which tackles the constraints of unbalanced medical development so that people’s ever-growing medical demand can be supplied. With the reality of over 10 years’ ophthalmology standardized resident training experience in China, certain crucial issues are put forward, such as the selection and training of teachers, the implementation of clinical training course, the concern of teachers’ salary and promotion, the residents’ capabilities of diagnosis and treatment including humanistic care, etc. This article discusses the root causes of those issues and the solutions to them, intending to implement the standardized resident training as a basic clinic medical engineering through the New Healthcare Reform
视网膜退行性疾病的种类繁多、患病人口基数大,该病特征为终末期严重的视网膜细胞丢失。视网膜类器官(retinal organoid,RO)可通过3D干细胞体外分化培养技术大量获取,并拥有完整的各亚型视网膜细胞和经典的视网膜分层结构。因此,RO可作为最佳的视网膜退行性疾病建模方法之一,以便于发现潜在致病机制。目前,RO衍生物已被广泛用于视网膜细胞替代治疗的动物实验和临床研究,具体的成效参差不齐,可能的影响因素包括移植细胞数量、移植时间窗、移植工具等。随着RO相关研究的快速发展,视网膜退行性疾病在分子和个体上的诊断和治疗将进一步完善。
Retinal degenerative diseases, characterized by severe retinal cell loss at the end stage, are of various kinds and haunt vast amounts of patients. Retinal organoid (RO) with complete retinal cell subtypes and classic retinal stratification structures can be obtained in large quantities through stem cells in vitro 3D differentiation and culture method. Therefore, RO can serve as one of the best ways for retinal degenerative disease modeling to facilitate the decipherment of underlying pathogenic mechanisms. At present, RO derivatives have been widely used in animal experiments and clinical studies of retinal cell replacement therapy with varying results possibly affected by cell quantity, time window, or tools in terms of transplantation. With the booming progress of RO-related research, the diagnosis and treatment on molecular and individual level for retinal degenerative diseases will be further improved.