Optimization of phage heptapeptide library-screening process for developing inhibitors of the isocitrate lyase homologue from Mycobacterium tuberculosis

The aims of this study were to screen peptide inhibitors specific for isocitrate lyase (ICL) using a phage peptide library and computer molecular docking and to explore the relevant mechanisms. Using ICL as a target, the phage peptide library was screened to obtain peptides with specific binding affinity. Based on the three-dimensional crystal structure of ICL(pdb:1F8I), the obtained polypeptides were docked to the 1F8I using the computer-simulated molecular docking technique. The successfully docked polypeptides were synthesized using the Fmoc solid-phase synthesis method, and the ICL inhibition rate of these peptides was measured. Finally, the possible mechanism underlying the inhibition was explored by Binding Site Analysis. A total of 29 heptapeptides were obtained through screening the phage peptide library. We found that 12 out of the 29 peptides were successfully docked to the 1F8I, and all 12 peptides could obviously inhibit the ICL activity, of which three heptapeptides showed an inhibiting (extent of inhibition over 50 %), IC50 value of 126 μM. Structural analysis revealed that the ICL tetramer has a large cavity in the center, and the polypeptides bind to ICL at amino acid residue 119’s GLN of the ICL monomer. We successfully obtained peptide inhibitors specific for ICL, and analyzed the mechanism underlying the interaction between the peptides and ICL. Our study provides scientific evidence for the development of antituberculosis peptide drugs targeting ICL.     

Relationships between the larval growth inhibition ofCaenorhabditis elegans by apigenin derivatives and their structures

Due to consumer reluctance to take synthetic drugs for nematode infections and the appearance of resistance to anthelminthic drugs, new drugs from natural products must be developed. Caenorhabditis elegans is one of the freely living nematodes and serves as a good model system for screening anthelminthic drugs. In this study, thirteen flavonoid derivatives were tested for anthelminthic activity and the relationships between their activities and structures were investigated. The structural information combined with the data for the larval growth inhibition of C. elegans provided meaningful structural insights in the search for new anthelminthic drugs.     

Safety,tolerability, and pharmacokinetics of ICL670, a new orally active iron-chelating agent in patients with transfusion-dependent iron overload due to beta-thalassemia

ICL670 is an orally active representative of a new class of tridentate iron chelator developed for the treatment of blood transfusion-dependent iron overload in chronic anemias. In this randomized, double-blind study, patients with transfusion-dependent beta-thalassemia received single oral doses of ICL670 ranging from 2.5 to 80 mg/kg to investigate its safety, tolerability, and pharmacokinetics and to obtain preliminary information on pharmacodynamic effects. ICL670 was well tolerated, and no safety problems occurred up to 80 mg/kg. A plasma half-life of 11 to 19 hours was found for ICL670, supporting once-daily oral administration. AUC0-24 h and Cmax of ICL670 increased nearly proportionally with the dose. The urinary excretion of ICL670 and its iron complex was less than 0.1% of the dose, and this was in accordance with the expected predominant iron fecal excretion induced by ICL670 (based on preclinical experiments). Notwithstanding, a positive trend toward increased amounts of urinary excreted iron was observed when the AUC0-24 h of ICL670 and the iron complex exceeded specific threshold values at the 40- and 80-mg/kg dose levels.     

In vitro blood distribution and plasma protein binding of the iron chelator deferasirox (ICL670) and its iron complex Fe-[ICL670]2 for rat, marmoset, rabbit, mouse, dog, and human.

Deferasirox (Exjade, ICL670) is an orally active iron chelator. Two molecules of deferasirox can form a complex with ferric iron (Fe-[ICL670]2) that can be excreted, reducing body iron overload. The blood binding parameters across species and the interaction with human serum albumin were analyzed for deferasirox and its iron complex. Both molecules were very highly bound to plasma proteins in all the tested species with unbound fractions in plasma in the range of 0.4 to 1.8% and 0.2 to 1.2% for deferasirox and Fe-[ICL670]2, respectively; binding of the iron complex was either similar or higher in all the species. The high plasma protein binding was in line with a distribution mainly into the plasma fraction of blood; the fraction in plasma was around 100% for Fe-[ICL670]2 in all the species and 65 to 95% for deferasirox depending on the species. Investigations with isolated proteins pointed to serum albumin as the principal binding protein for deferasirox and its iron complex in human plasma. Competition binding experiments indicated that deferasirox at high concentrations displaced markers from the two main drug binding sites of human albumin, whereas Fe-[ICL670]2 displaced only warfarin. In the context of the pharmacokinetic properties of deferasirox and Fe-[ICL670]2, the data indicate the importance of plasma protein binding for their disposition and support a comparison of the pharmacokinetics of deferasirox and its iron complex across species. The low likelihood of clinically relevant drug displacement by deferasirox in plasma is discussed.     

The new orally active iron chelator ICL670A exhibits a higher antiproliferative effect in human hepatocyte cultures than O-trensox

By comparing the antiproliferative effect of the iron chelators ICL670A and O-trensox in the human hepatoma cell line HUH7 and human hepatocyte cultures, we have shown that ICL670A decreased cell viability, inhibited DNA replication and induced DNA fragmentation more efficiently than O-trensox. O-trensox and ICL670A induced a cell cycle blockade in G0-G1 and S phases respectively. In parallel, ICL670A inhibited polyamine biosynthesis by decreasing ornithine decarboxylase and spermidine/spermine N(1)-acetyltransferase activities. O-trensox increased polyamine biosynthesis and particularly putrescine level by stimulating spermidine-spermine N(1)-acetyltransferase activity which could activate the polyamine retro-conversion pathway. Moreover, the two chelators exhibit some cytotoxic effect in the two culture models; ICL670A was more cytotoxic than O-trensox and higher concentrations of the two chelators were necessary to induce a cytotoxicity in primary cultures versus hepatoma cells. These results suggested that ICL670A has the most efficient antitumoral effect, blocks cell proliferation by a pathway different of O-trensox and may constitute a potential drug for anticancer therapy.     

Sorting functions of the individual cytoplasmic domains of the G protein-coupled vasopressin V(2) receptor in Madin Darby canine kidney epithelial cells

Previous studies have shown that the G protein-coupled human vasopressin V(2) receptor (V(2) receptor) is expressed predominantly in the basolateral membrane of Madin Darby canine kidney type II (MDCKII) epithelial cells at steady state. Here we have assessed the influence of the individual cytoplasmic domains of the V(2) receptor on polarized sorting in MDCKII cells. The second (ICL2) and third (ICL3) intracellular loops and the C-terminal tail were fused separately to a green fluorescent protein-tagged receptor fragment comprising the first transmembrane domain and flanking regions. We show that the ICL2 domain of the V(2) receptor alone promotes basolateral cell surface expression and thus seems to contain the basolateral sorting signal of the V(2) receptor. Fusion of the other cytoplasmic domains, however, does not lead to a randomized cell surface expression. The C-terminal tail of the V(2) receptor promotes apical targeting. Fusion of ICL3 leads to a receptor fragment that is retained in the endoplasmic reticulum (ER). The results are consistent with a model in which the V(2) receptor contains signals for both apical and basolateral cell surface expression, the latter being dominant. Furthermore, ICL3 may contain a RXR [corrected] ER retention signal, which is not accessible in the correctly folded full-length receptor but which is unmasked when ICL3 is fused alone.     

Development of tridentate iron chelators: from desferrithiocin to ICL670

Successful treatment of beta-thalassemia requires two key elements: blood transfusion and iron chelation. Regular blood transfusions considerably expand the lifespan of patients, however, without the removal of the consequential accumulation of body iron, few patients live beyond their second decade. In 1963, the introduction of desferrioxamine (DFO), a hexadentate chelator, marked a breakthrough in the treatment of beta-thalassemia. DFO significantly reduces body iron burden and iron-related morbidity and mortality. DFO is still the only drug for general use in the treatment of transfusion dependent iron overload. However, its very short plasma half-life and poor oral activity necessitate special modes of application (subcutaneous or intravenous infusion) which are inconvenient, can cause local reactions and are difficult to be accepted by many patients. Over the past four decades, many different laboratories have invested major efforts in the identification of orally active iron chelators from several hundreds of molecules of synthetic, microbial or plant origin. The discovery of ferrithiocin in 1980, followed by the synthesis of the tridentate chelator desferrithiocin and proof of its oral activity raised a lot of hope. However, the compound proved to be toxic in animals. Over a period of about fifteen years many desferrithiocin derivatives and molecules with broader alterations led to the discovery of numerous new compounds some of which were much better tolerated and were more efficacious than desferrithiocin in animals, however, none was safe enough to proceed to the clinical use. The discovery of a new chemical class of iron chelators: The bis-hydroxyphenyltriazoles re-energized the search for a safe tridentate chelator. The basic structure of this completely new chemical class of iron chelators was discovered by a combination of rational design, intuition and experience. More than forty derivatives of the triazole series were synthesized at Novartis. These compounds were evaluated, together with more than 700 chelators from various chemical classes. Using vigorous selection criteria with a focus on tolerability, the tridentate chelator 4-[(3,5-Bis-(2-hydroxyphenyl)-1,2,4)triazol-1-yl]-benzoic acid (ICL670) emerged as an entity which best combined high oral potency and tolerability in animals. ICL670 is presently being evaluated in the clinic.     

有晶状体眼后房型人工晶状体术与SMART 术矫治中低度近视术后效果及视觉质量的比较

目的探究中低度近视有晶状体眼后房型人工晶状体(ICL)手术矫治与SMART手术矫治术后效果及视觉质量的变化。方法选取2019年1月至2020年1月武汉汉阳艾格眼科医院中低度近视病人148例(148眼),随机数字表法分为ICL组(74例,74眼)和SMART组(74例,74眼)。ICL组施行ICL,SMART组施行SMART。统计两组并发症及术前、术后1周、1个月、6个月最佳矫正视力(BVCA)、裸眼视力(UCVA)、安全指数、有效指数、视觉质量［客观散射指数(OSI)、MTF截止频率(MTF cut?off)、斯特列尔比(SR)］、对比敏感度［低频段(3 cpd)、中频段(6 cpd)、中频段(12 cpd)］、全眼像差(垂直彗差、球差、总高阶像差)、眼血流动力学参数［眼动脉(OA)、睫状后动脉(PCA)舒张末期流速(Vd)、收缩期血流速度峰值(Vs)］。结果术前、术后1周、1个月、6个月两组BVCA、UCVA、安全指数、有效指数比较,差异无统计学意义(P>0.05),术后1个月、6个月两组BVCA［ICL组(?0.77±0.06)、(?0.84±0.07)比(0.49±0.05),SMART 组(?0.76±0.09)、(?0.82±0.08)比(0.50±0.03)］、UCVA［ICL 组(0.72±0.08)、(0.65±0.10)比(0.95±0.22),SMART组(0.70±0.10)、(0.67±0.12)比(0.93±0.25)］优于其术前(P<0.017);术后1周、1个月、6个月ICL组OSI低于SMART组,MTF cutoff、SR高于SMART组(P<0.05);术后1周、1个月、6个月ICL组明光无眩光状态下3cpd、6 cpd、12 cpd对比敏感度高于SMART组(P<0.05);术后1周、1个月、6个月ICL组总高阶像差低于SMART组(P<0.05);术前、术后1周、术后1个月、6个月两组眼血流动力学指标比较,差异无统计学意义(P>0.05);术后6个月内,两组haze、光晕、眼压升高等并发症发生率比较,差异无统计学意义(P>0.05)。结论ICL术、SMART均对中低度近视具有良好矫正作用,特别是ICL,有助于增加对比敏感度,提高视觉质量。     

Histone H2AX phosphorylation as a molecular pharmacological marker for DNA interstrand crosslink cancer chemotherapy

The aims of this study were to investigate mechanisms of action involved in H2AX phosphorylation by DNA interstrand crosslinking (ICL) agents and determine whether gammaH2AX could be a suitable pharmacological marker for identifying potential ICL cellular chemosensitivity. In normal human fibroblasts, after treatment with nitrogen mustard (HN2) or cisplatin, the peak gammaH2AX response was detected 2-3 h after the peak of DNA ICLs measured using the comet assay, a validated method for detecting ICLs in vitro or in clinical samples. Detection of gammaH2AX foci by immunofluorescence microscopy could be routinely detected with 6-10 times lower concentrations of both drugs compared to detection of ICLs using the comet assay. A major pathway for repairing DNA ICLs is the initial unhooking of the ICL by the ERCC1-XPF endonuclease followed by homologous recombination. HN2 or cisplatin-induced gammaH2AX foci persisted significantly longer in both, ERCC1 or XRCC3 (homologous recombination) defective Chinese hamster cells that are highly sensitive to cell killing by ICL agents compared to wild type or ionising radiation sensitive XRCC5 cells. An advantage of using gammaH2AX immunofluorescence over the comet assay is that it appears to detect ICL chemosensitivity in both ERCC1 and HR defective cells. With HN2 and cisplatin, gammaH2AX foci also persisted in chemosensitive human ovarian cancer cells (A2780) compared to chemoresistant (A2780cisR) cells. These results show that gammaH2AX can act as a highly sensitive and general marker of DNA damage induced by HN2 or cisplatin and shows promise for predicting potential cellular chemosensitivity to ICL agents.     

Predictive 3D-QSAR and HQSAR model generation of isocitrate lyase (ICL) inhibitors by various alignment methods combined with docking study

Isocitrate lyase (ICL) is one of the most important targets in the treatment of Mycobacterium tuberculosis. In this study a diverse set of 2-benzanilide derivatives were aligned by two different methods for CoMFA, CoMSIA, and HQSAR analysis. The best CoMFA model was obtained with the internal validation value (q ²) of 0.730 and conventional coefficient (r ²) of 0.944. Various CoMSIA models were generated and cross-validated. The best cross-validation coefficient (q ²) value was found to be statistically satisfactory (0.688). Both the models were validated by test set of 10 compounds with satisfactory prediction value of (r ² _pred ) 0.725 and 0.631 for CoMFA and CoMSIA, respectively. Cross-validation coefficient value (q ²) of 0.694 and r ² of 0.856 were obtained for HQSAR study. The docking study reveals that large hydrophobic pockets occupy R substitutions of these compounds. An electronically negative surface is observed near R₁ substitution. The results of the 3D-QSAR analysis corroborate with the molecular docking results, and our findings will serve as a basis for further development of better allosteric inhibitors of ICL inhibitors against M. tuberculosis.     

Gemcitabine potentiates cisplatin cytotoxicity and inhibits repair of cisplatin-DNA damage in ovarian cancer cell lines

Synergistic cytotoxicity between cisplatin and the nucleoside analog gemcitabine was observed in a panel of cisplatin-sensitive (2008, A2780) and -resistant (2008/C13*5.25, A2780/CP70) human ovarian cell lines. Previous studies have suggested a role for DNA repair in the mechanism of synergy between the two drugs. We therefore further investigated the hypothesis that the synergistic cytotoxicity between gemcitabine and cisplatin in these cell lines may be caused by gemcitabine-mediated inhibition of cisplatin intrastrand adduct (IA) and interstand cross-link (ICL) repair. The effect of gemcitabine on the accumulation and repair of cisplatin IA and ICL in each cell line was then measured directly using gene-specific quantitative polymerase chain reaction and denaturation/renaturation techniques, respectively. Pretreatment of 2008 cells with 1 microM gemcitabine for 2 h before exposure to cisplatin for 7 h enhanced the accumulation of cisplatin IA and ICL by 50 and 40%, respectively (P < 0.05), above that induced by cisplatin alone. To investigate the possibility that the increased accumulation of cisplatin lesions was caused by inhibition of removal of cisplatin damage, 2008 cells were incubated with 200 microM cisplatin for 5 h in the presence and absence of gemcitabine and then a further 8 h in the absence of cisplatin. Only 57% IA were removed in the combination treated cells compared with 74% in cisplatin control cells. Similarly, repair of cisplatin ICL was inhibited in the gemcitabine-treated cells compared with the cells treated with cisplatin only (60 versus 72%). These findings demonstrate a direct inhibitory effect of gemcitabine on the repair of cisplatin IA and ICL and suggest a mechanistic basis for the cytotoxic synergy between the two drugs.     

高度近视合并白内障后房型PIOL植入对眼轴测量、内轴向结构稳定的影响

目的 观察高度近视合并白内障植入不同后房型有晶状体眼人工晶状体(phakic intraocular lens,PI-OL)对眼轴测量及内轴向空间结构稳定性的影响.方法 2012年7月—2015年7月对106例(168只眼)行白内障超声乳化吸出术联合PIOL植入术,根据患者植入PIOL类型分为有晶状体眼屈光镜(phakic refractive lens,PRL)组81只眼和可植入式接触镜(implantable collamer lens,ICL)组87只眼.测量两组手术前、后眼轴长度并分析其相关性,观察手术前、后前房深度的变化.结果 两组术后眼轴长度和最佳矫正视力均较术前提高,PRL组术后眼轴长度长于ICL组,但术后最佳矫正视力低于ICL组(P<0.05).手术前、后眼轴长度差值PRL组随着眼轴的延长而逐渐缩小,ICL组随着眼轴的延长而逐渐增大,但波动范围较小.两组术后前房深度小于术前,但PRL组大于ICL组(P<0.05).结论 后房型PIOL植入对高度近视合并白内障患者的眼轴测量影响较小,有利于眼内轴向空间结构的稳定,但不同材质的PIOL对内轴向结构的稳定性不同.     

A high throughput screening approach to identify isocitrate lyase inhibitors from traditional Chinese medicine sources

Isocitrate lyase (ICL) catalyses the first step of the glyoxylate bypass pathway, which reversibly cleaves isocitrate into succinate and glyoxylate. This pathway occurs in a wide range of pathogens and plays a key role in the pathogenesis of Mycobacterium tuberculosis (MTB) suggesting that it may represent a drug target for the treatment of tuberculosis. ICL was cloned, expressed, and purified, and a high‐throughput screen (HTS) developed to screen active extracts derived from traditional Chinese medicines (TCMs) for inhibition of ICL. A colorimetric assay based on the formation of glyoxylate‐phenylhydrazone was used to measure ICL activity. The assay had signal to noise (S/N) of 12.74 and Z′ factor of 0.72, indicating that the assay was suitable for HTS. Screening of a collection of 465 extracts derived from TCMs resulted in the identification of two extracts from Illicium verum Hook.f (Illiciaceae, XHD‐1) and Zingiber officinale Rosc (Zingiberaceae, XHD‐2), which inhibited ICL with IC₅₀ values of 47.7 ± 16.9 and 18.2 ± 0.9 µg/ml, respectively. Drug Dev. Res. 67:818–823, 2006. © 2007 Wiley‐Liss, Inc.     

Immunoreactive LH in long‐term frozen human urine samples

Urine provides a convenient non‐invasive alternative to blood sampling for measurement of certain hormones. Urinary luteinizing hormone (LH) measurements have been used for endocrinology research and anti‐doping testing. However, the commercially available LH immunoassays are developed and validated for human blood samples but not urine so that LH assays intended for use with urine samples need thorough validation. Therefore, the present study evaluated the measurement of urinary LH immunoreactivity using previously validated immunofluorometric (IF) and immunochemiluminometric (ICL) LH assays after prolonged frozen storage. LH was measured in serial urine samples following administration of a single injection of one of two doses of recombinant human chorionic hormone (rhCG) with assays run at the end of study (2008) and again after four years of frozen (‐20 °C) storage where samples were stored without adding preservatives. The ICL assay showed quantitatively reproducible LH measurements after prolonged ‐20 °C storage. However, the IF immunoassay gave consistently lower LH levels relative to ICL (2008) with a further proportionate reduction after four years of sample storage (2012). Yet, both the assays displayed similar patterns of the time‐course of urine LH measurement both before and after four years of frozen storage. In conclusion, we found that both immunoassays are suitable for urinary LH measurements with ICL assay being more robust for quantitative urinary LH measurement such as for anti‐doping purposes, whereas the IF could be applicable for research studies where urine LH levels are compared within‐study but not in absolute terms. Copyright © 2013 John Wiley & Sons, Ltd.     

新型红霉素类大环内酯衍生物的合成及抗菌活性研究

目的 对大环内酯类抗生素进行结构改造，拟筛选获得抗菌活性更高的候选药物；方法 分别对氟红霉素和克拉霉素的C-3及C-11，C-12进行结构修饰，设计合成了17个大环内酯类衍生物，采用微量稀释法测定了衍生物的最低抑菌浓度(MIC)。结果 12d、12e和12f对B. subtilis 168和 S. aureus USA 300表现出了较好的抗菌活性；结论 通过结构改造获得了抗菌活性增强的大环内酯类衍生物，进一步探讨了大环内酯类抗生素的构效关系，为后续研究提供了参考。     

以异柠檬酸裂解酶为靶点筛选抗持留结核分枝杆菌药物

进入21世纪，结核病仍然是临床上发病率和死亡率最高的传染病之一。目前，结核分枝杆菌（Mycobacterium tuberculosis）的多重耐药，以及在抗结核药物作用过程中结核分枝杆菌的持留状态，已成为全世界结核病控制工作的主要障碍。异柠檬酸裂解酶（isocitrate lyase，ICL）是乙醛酸循环途径中的关键限速酶之一，决定了结核分枝杆菌的持留性。在文中我们将描述异柠檬酸裂解酶的基本性质及结构特征，希望能通过对ICL抑制剂作用区域的了解来推动抗持留结核分枝杆菌药物的研究。     

High-throughput analysis of DNA interstrand crosslinks in human peripheral blood mononuclear cells by automated reverse FADU assay

DNA interstrand crosslinks (ICL) are induced both by several cytotoxic anti-cancer drugs as well as by the chemical warfare agent sulphur mustard (SM). Although measurement of ICL formation could be used in risk assessment or provide valuable predictive information on the response of malignant cells to crosslinking chemotherapeutic agents, respectively, it is currently not applied due to lack of appropriate standardized methodology. Here we describe a fast and convenient procedure for detection of ICL in human peripheral blood mononuclear cells (PBMC) as high-throughput method, termed 'reverse FADU assay'. This assay detects ICL based on the prevention of time-dependent alkaline unwinding of double-stranded DNA in a cell lysate that starts from single or double strand breaks. We have successfully established and optimized the reverse FADU assay by using human PBMC exposed to the model compounds mitomycin C, melphalan and SM. Our fully automated assay version is faster than currently used methods and possesses similar sensitivity. It operates in a 96-well format, thus allowing parallel analysis of multiple samples. Furthermore, we describe optimized protocols for sample preparation, with sample volume minimized to 100μl of blood, storage and shipment conditions. We conclude that the reverse FADU assay is an attractive candidate method for monitoring DNA damage induced by DNA crosslinking agents.     

Synthesis of new 2-thiouracil-5-sulphonamide derivatives with antibacterial and antifungal activity

2-Thiouracil-5-sulphonic acid N-(4-acetylphenyl) Amide (1) was reacted with a series of aromatic aldehydes giving chalcones 2 (Claisen-Schemidt reaction), some of these chalcones were reacted with urea and thiourea giving pyrimidine-2-one and pyrimidine-2 thione derivatives respectively of the type 3a,b and 4a,b. In addition many chalcones were reacted with hydroxylamine hydrochloride giving isoxazoline derivatives 5a,b. They could also reacted with phenylhydrazine to give pyrazoline derivatives 6a,b, chalcones also were reacted withethylcyano acetate and/or malononitryl in pyridine giving pyran derivatives 7a,c and 8a,c. In another pathway chalcones were epoxidised by H2O2 giving epoxides 9a,c which in turn were reacted with phenylhydrazine giving 4-hydroxypyrazoline derivatives 10a,c. In another reaction chalcones were reacted with ethylcyanoacetate in presence of amm.acetate giving pyridone derivatives 11a,d which could be prepared also in exellent yield from compound 1 by its reaction with certain aromatic aldehydes and ethylcyanoacetate in presence of ammonium acetate. Finally, compound 1 was reacted with semicarbazide giving semicarbazone intermediate 12 which in turn was reacted with thionyl chloride giving thiadiazole derivative 13. The biological effects of some of the new synthesized compounds were also investigated.     

Gossypol and derivatives: a new class of aldose reductase inhibitors

Gossypol and 17 derivatives were tested as inhibitors of aldose reductase from human placenta. Gossypol and a number of the derivatives were potent inhibitors. The order of inhibitory activity was interpreted in relation to the Kador-Sharpless pharmacophor model for the aldose reductase inhibitor site. The structural but not the electronic aspects of the model were found to apply to this series of compounds.     

有晶状体眼后房屈光晶状体植入术治疗超高度近视的临床观察

目的：探讨有晶状体眼后房屈光晶状体植入术治疗超高度近视眼的有效性、安全性及可预测性。方法217例（381只眼）超高度近视眼（-15.00±-5.00）DS患者植入后房屈光晶状体（ICL）。术后1周观察患者的裸眼视力比术前最佳矫正视力提高一行及一行以上者占78.74%（300/381）;术后6个月比术前最佳矫正视力提高一行及一行以上者占89.50%（341/381）术后12个月比术前最佳矫正视力提高一行及一行以上者98.68%（376/381）;6个月时与12个月的裸眼视力没有改变;患者角膜内皮细胞计数,眼压术后6、12个月时与术前相比,差异均无统计学意义（P〉0.05）。前房深度术前与术后≥6个月比较,差异有统计学意义（P〈0.05）;术后≥12个月与术后≥6个月比较,差异无统计学意义（P〉0.05）;晶体ICL拱高为0.52-0.86mm,平均拱高（0.626±0.248）mm,1例ICL后表面与自身晶状体相贴。1个月时16眼ICL表面炎性反应物沉积;1眼瞳孔呈轻度椭圆形。13眼主诉夜间出现眩光症状,其他患者均无明显不适满意程度较高。结论有晶状体眼后房屈光晶状体（ICL）植入术矫正超高度近视眼具有良好的有效性、安全性及可预测性。