朱思泉
从事白内障及眼科其他临床与科研工作以及医用人工材料学研究
个性化签名
- 姓名:朱思泉
- 目前身份:
- 担任导师情况:
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学术头衔:
博士生导师
- 职称:-
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学科领域:
眼科学
- 研究兴趣:从事白内障及眼科其他临床与科研工作以及医用人工材料学研究
朱思泉
个人简历:
男,生于1963年6月,医学博士、北京同仁医院眼科主任医师、北京同仁医院眼科白内障中心主任、北京科技大学兼职教授、博士研究生导师。1981年毕业于泸州医学院,1991年考取中山医科大学攻读眼科学硕士学位,毕业后在中山医科大学附属第三医院眼科担任眼科副主任、副教授。1998年作为白内障访问学者赴美国新墨西哥州东方眼科中心学习。2002年来到首都医科大学附属北京同仁医院眼科白内障中心工作,2003年考取首都医科大学眼科学在职博士研究生,现任北京同仁医院白内障中心主任、眼科中心经营主任、眼科中心临床部主任助理、《解放军医学杂志》特邀编委、中华音像出版社眼科版编委、中华博爱基金会同仁博爱光明工程负责人,并于2006年被聘为北京科技大学材料科学与工程学院兼职教授,2010年担任北京科技大学材料科学与工程学院兼职博士生导师。
从事白内障及眼科其他临床与科研工作以及医用人工材料学研究16年,独创了辅助钩,改良了双板层角膜切口,拉网式皮质抽吸术,定向对冲挤压快速碎核法,高真空低能量囊上快速劈核法等系列超声乳化新技术,并首先提出了“微创白内障治疗体系”、“功能性人工晶体”、“功能性人工角膜”等概念,主持完成了广东省科委、卫生厅、市科委等各级基金资助课题4项,参与了卫生部等课题的研究2项。2004年获得国家自然科学基金项目《中国人不同民族先天性白内障致病基因定位》,编号:30471864。2006年获得国家科技部“十一五”科技支撑计划重大项目《高效智能化微创白内障治疗系统研制》,编号:2006BAI03A09。已发表论文50余篇,先后在美国白内障会议、世界华人眼科大会、OSN亚洲白内障会议、全国眼科会议和亚洲白内障会议等进行大会演讲。参与编写专著《眼科超声生物显微镜》、《北京同仁医院眼科专题讲座》等。
目前承担科研情况:
1.适合人眼晶状体的高分子材料研究(2102021),北京市自然科学基金,2010.1~2012.12,项目负责人。
2.功能性人工晶状体材料的生物相容性研究,高等学校博士学科点专项科研基金,2010.1~2012.12,项目负责人。
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20
朱思泉, Li Song, † Wang Hu, † Hongbin Zhang, † Guojie Wang, *, † Huai Yang, † and Siquan Zhu*, †, ‡
J. Phys. Chem. B 2010, 114, 7172-7178,-0001,():
-1年11月30日
Acrylates have been used in ophthalmic practice as a paradigmatic implant material for decades, especially as intraocular lens for their excellent transparency. A novel polymeric shape memory system of chemically cross-linked acrylate-methacrylate copolymer networks was developed and characterized in this study. The thermomechanical properties, shape memory properties, transparency, and surface wettability as well as cytotoxicity were systematically evaluated to mimic the in vivo situation by differential scanning calorimetry (DSC), tensile tests, spectrophotometer, Abbe refractometer, contact angle measurements, and MTT assay. It was found that the chemically cross-linked copolymer network behaves as an elastomer capable of arbitrary shaping above the glass-transition temperature. Transition temperatures of the networks were tunable through the change of the composition of monomers.
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【期刊论文】Synthesis and characterization of reactive poloxamer 407s for biomedical applications
朱思泉, Guoguang Niu a, Fengyi Du c, Li Song a, Hongbin Zhang a, Jun Yang c, Hui Cao a, Yudong Zheng a, Zhou Yang a, Guojie Wang a, Huai Yang a, *, Siquan Zhu b
Journal of Controlled Release 138 (2009) 49-56,-0001,():
-1年11月30日
The drawbacks of poloxamer hydrogel, such as dissolving quickly in aqueous solution, have limited its biomedical application. In order to improve the stability of hydrogel, a novel system was developed by combining the reversible thermo-sensitive property of poloxamer 407 and the thiol-ene reactivity between the acrylate and thiol groups. It was found that the sol–gel transition of the acrylate/thiol modified poloxamer 407 mixture could be achieved at body temperature even with a low concentration of 17.5 wt.%. Meanwhile, the reaction between the acrylate and thiol modified poloxamer 407s occurred spontaneously in mimic physiological conditions, thus the hydrogel with crosslinking structure was formed. As a result, the stability of the crosslinked hydrogel was enhanced remarkably, and the release time of the drug from the crosslinked hydrogel was about 4.0 times as long as that from the poloxamer 407 hydrogel. In vitro and in vivo experiments revealed that the iocompatibilities of the modified poloxamer 407 hydrogel were similar to that of poloxamer 407. These results indicate that the modified poloxamer 407s have potential applicationsin controlled drug release, tissue engineering and cell encapsulation etc.
Poloxamer Hydrogel Thiol-ene reaction Thermo-sensitive Controlled release
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朱思泉, Guoguang Niu a, Ying Yang c, Hongbin Zhang a, Jun Yang c, Li Song a, Miki Kashima a, Zhou Yang a, Hui Cao a, Yudong Zheng a, Siquan Zhu b, *, Huai Yang a
Acta Biomaterialia 5 (2009) 1056-1063,-0001,():
-1年11月30日
Injectable acrylamide/N-vinylpyrrolidinone copolymers with pendent thiol groups were prepared by a radical polymerization and reductive dissolution reaction. The solution of copolymers was re-gelled through oxidation in air or the thiol–disulfide exchange reaction. The re-gelation time could be adjusted from several minutes to several hours by changing the amount of the disulfide exchange reagent. The re-gelled hydrogels possessed high transmittance in the visible region but could block out some of the ultraviolet radiation. Their refractive indexes ranged from 1.34 to 1.35, and their equilibrium water contents were over 95.0%. The morphologies of the hydrogels were analyzed and the porous structure, with pore sizes of 50–300 lm, was noted. The cytotoxicities of the hydrogels were clearly reduced compared with previous results. The experimental results indicated that the injectable copolymers could be used as an artificial vitreous substance or as a scaffold for lens regeneration.
Disulfide bond, Hydrogel, Vitreous substance, Lens regeneration
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【期刊论文】Thiol/Acrylate-Modified PEO-PPO-PEO Triblocks Used as Reactive and Thermosensitive Copolymers
朱思泉, Guoguang Niu, Hongbin Zhang, Li Song, Xiaopeng Cui, Hui Cao, Yudong Zheng, Siquan Zhu, *, † Zhou Yang, and Huai Yang*
Biomacromolecules 2008, 9, 2621-2628,-0001,():
-1年11月30日
The reactive thermal-sensitive hydrogels, which combined the reversible thermosensitive and mild reactive property, were designed based on thiol-ene reaction in physiological conditions between thiol and acrylate capped thermosensitive Poloxamer 188. The modified P188A, P188SH, and their reactivity were characterized by 1H NMR, FT-IR, GPC, DSC, Ellman method, and Rheometer. It was found that the thiol-ene reaction was pH and thermal-sensitive. There was 77.7% SH involved into the reaction at 37.0 °C and pH 7.4 within the first 30 min. The most of molecules reacted as CdC/SH mol ratio was 1.5. The exothermic thiol-ene reaction was mild, with about ΔH ) -91.18 J/g changes. The multiblocks or network structure limited the dissolution of hydrogel, correspondingly the gel’s duration and the release time of methylene blue were prolonged to 124 h. The experimental results indicated the reactive thermal-sensitive hydrogel’s potential applications in drug delivery, tissue engineering, and cell encapsulation.
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【期刊论文】A new mutation in BFSP2 (G1091A) causes autosomal dominant congenital lamellar cataracts
朱思泉, Xu Ma, , Fei-Feng Li, Shu-Zhen Wang, Chang Gao, Meng Zhang, Si-Quan Zhu
Molecular Vision 2008; 14: 1906-1911,-0001,():
-1年11月30日
Purpose: We sought to identify the genetic defect in a four-generation Chinese family with autosomal dominant congenital lamellar cataracts and demonstrate the functional analysis with biosoftware of a candidate gene in the family. Methods: Family history data were recorded. Clinical and ophthalmologic examinations were performed on family members. All the members were genotyped with microsatellite markers at loci considered to be associated with cataracts. Two-point LOD scores were calculated by using the Linkage Software after genotyping. A mutation was detected by using gene-specific primers in direct sequencing. Wild type and mutant proteins were analyzed with Online Bio-Software. Results: Affected members of this family had lamellar cataracts. Linkage analysis was obtained at markers D3S2322 (LOD score [Z]=7.22, recombination fraction [θ]=0.0) and D3S1541 (Z=5.42, θ=0.0). Haplotype analysis indicated that the cataract gene was closely linked to these two markers. Sequencing the beaded filament structural protein 2 (BFSP2) gene revealed a G>A transversion in exon 5, which caused a conservative substitution of Arg to His at codon 339 (P.R339H). This mutation cosegregated with the disease phenotype in all affected individuals and was not observed in the unaffected family members or in 100 normal, unrelated individuals. Bioinformatic analyses showed that a highly conserved region was located around Arg339. Data generated with Online Bio-Software revealed that the mutation altered the protein’s hydrophobicity, hydrophobic moment, and chaperone and regulation activities. Conclusions: This is the first reported case of a congenital lamellar cataract phenotype associated with the mutation of Arg339His (P.R339H) in BFSP2. It highlights the physiologic importance of the beaded filament protein and demonstrates a possible mechanism of action for the mutant gene.
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朱思泉, Fei-feng Li, , Si-quan Zhu, Shu-zhen Wang, Chang Gao, Shang-zhi Huang, Meng Zhang, Xu Ma
Molecular Vision 2008; 14: 750-755,-0001,():
-1年11月30日
Purpose: We sought to identify the genetic defect in a large, five-generation Chinese family with autosomal dominant progressive polymorphic congenital coronary cataracts and to examine the clinical features in detail. Methods: Clinical and ophthalmologic examinations were conducted on family members. All members were genotyped with microsatellite markers at loci previously associated with cataracts. Two-point LOD scores were calculated using a linkage package after genotyping. A mutation was detected by direct sequencing and verified by denaturing highperformance liquid chromatography (DHPLC). Results: Clinical observations showed that all affected family members had progressive polymorphic coronary cataracts. Linkage analysis was obtained at markers, D22S303 (LOD score [Z]=2.11, recombination fraction [θ]=0.0) and D22S1167 (Z=1.20, θ=0.0). Haplotype analysis indicated that the cataract gene was closely linked with these two markers. Sequencing the βB-crystallin gene (CRYBB2) revealed a C → T transition in exon 6, which changed a codon from Gln to a stop codon (P.Q155X). This mutation cosegregated with all affected individuals and was not observed in any unaffected family member or 100 normal, unrelated individuals. Conclusions: This study identified a mutation in CRYBB2 in a large Chinese family with autosomal ominant progressive polymorphic congenital coronary cataracts. These results provide evidence that CRYBB2 is a pathogenic gene for congenital cataracts; at the same time, congenital cataracts are a clinically and genetically heterogeneous lens condition.
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朱思泉, Feng Gu, , Weixiao Luo, Xin Li, Zhuoqun Wang, Shuang Lu , Meng Zhang, Baojian Zhao, Siquan Zhu, Shan Feng, Yong-bin Yan, Shangzhi Huang, *, and Xu Ma
HUMAN MUTATION Mutation in Brief #1001 (2008) Online,-0001,():
-1年11月30日
Hereditary cataract is a phenotypically and genetically heterogeneous lens disease that is responsible for a significant proportion of the visual impairment and blindness that occurs in children. In a five-generation Chinese family with autosomal dominant inherited congenital cataract, clinical examination showed three cataract phenotypes: punctuate, nuclear, and total cataracts. Linkage analysis was performed and positive two-point LOD scores (with maximum of 4.43 and 4.27 at θ= 0) were obtained for markers D21S1411 and D21S1890 on chromosome 21q22.3, flanking the CRYAA (alphaA-crystallin-encoding gene) locus. Sequencing of CRYAA revealed a novel heterozygous G>A transition (c.346G>A) inexon 3 that cosegregated with the disease phenotype and results in a conservative substitution of Arg to His at codon 116 (p.R116H). To understand the molecular basis of cataract formation, mutant and wild-type alphaA-crystallins were expressed in E. coli. RPHPLC (reverse phase-high-performance liquid chromatography) suggested an increased hydrophobicity of the mutant recombinant protein, compared to that of wild-type alphaAcrystallins. Furthermore, loss of chaperone activity of the mutant was seen in DTT (DLdithiothreitol)- induced insulin aggregation assay. FPLC (fast protein liquid chromatography) purification showed that the His-116 mutant protein had increased binding affinity to lysozyme. Gain of activated lysozyme binding, elevation of hydrophobicity and loss of chaperone activity of the mutant protein may be some of the molecular mechanisms underlying cataract in this large family.
AlphaA-crystallin,, CRYAA,, Linkage analysis,, Cataracts,, Chaperone
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【期刊论文】Mutation G61C in the CRYGD gene causing autosomal dominant congenital coralliform cataracts
朱思泉, Feifeng Li, , Shuzhen Wang, Chang Gao, Shiguo Liu, Baojian Zhao, Meng Zhang, Shangzhi uang, Siquan Zhu, Xu Ma
Molecular Vision 2008; 14: 378-386,-0001,():
-1年11月30日
Purpose: We sought to identify the genetic defect in a four-generation Chinese family with autosomal dominant congenital coralliform cataracts and demonstrate the functional analysis of a candidate gene in the family. Methods: Family history data were recorded. Clinical and ophthalmologic examinations were performed on affected and unaffected family members. All the members were genotyped with microsatellite markers at loci considered to be associated with cataracts. Two-point LOD scores were calculated using the Linkage software after genotyping. A mutation was detected by direct sequencing, using gene-specific primers. Wild-type and mutant proteins were analyzed with online software. Results: Affected members of this family had coralliform cataracts. Linkage analysis was obtained at markers, D2S72 (LOD score [Z]=3.31, recombination fraction [θ]=0.0) and D2S1782 (Z=3.01, θ=0.0). Haplotype analysis indicated that the cataract gene was closely linked to these two markers. Sequencing the γD-crystallin gene (CRYGD) revealed a G>T transversion in exon 2, which caused a conservative substitution of Gly to Cys at codon 61 (P.G61C). This mutation cosegregated with the disease phenotype in all affected individuals and was not observed in any of the unaffected or 100 normal, unrelated individuals. Bioinformatic analyses showed that a highly conserved region was located around Gly61. Data generated with online software revealed that the mutation altered the protein’s stability, solvent-accessibility, and interactions with other proteins.
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【期刊论文】A missense mutation S228P in the CRYBB1 gene causes autosomal dominant congenital cataract
朱思泉, WANG Jun, MA Xu, GU Feng, LIU Ning-pu, HAO Xiao-lin, WANG Kai-jie, WANG Ning-li and ZHU Si-quan
Chin Med J 2007; 120 (9): 820-824,-0001,():
-1年11月30日
Background Congenital cataract is a highly heterogeneous disorder at both the genetic and phenotypic levels. This study was conducted to identify disease locus for autosomal dominant congenital cataracts in a four generation Chinese family. Methods Family history and clinical data were recorded. All the members were genotyped with microsatellite markers which are close to the known genetic loci for autosomal congenital cataracts. Two-point Lod scores were obtained using the MLINK of the LINKAGE program package (ver 5.1). Candidate genes were amplified by polymerase chain reaction (PCR) and direct cycle sequencing. Results The maximum Lod score of Zmax=2.11 was obtained with three microsatellite markers D22S258, D22S315, and D22S1163 at recombination fraction θ= 0. Haplotype analysis showed that the disease gene was localized to a 18.5 Mbp region on chromosome 22 flanked by markers D22S1174 and D22S270, spanning the β-crystallin gene cluster. A c.752T-->C mutation in exon 6 of CRYBB1 gene, which resulted in a heterozygous S228P mutation in predicted protein, was found to cosegregate with cataract in the family. Conclusions This study identified a novel mutation in CRYBB1 gene in a Chinese family with autosomal dominant congenital cataract. These results provide strong evidence that CRYBB1 is a pathogenic gene for congenital cataract.
congenital cataract, microsatellite markers, linkage analysis, CRYBB1
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朱思泉, LY Qiao, , NL Wang, YB Liang, SQ Zhu, XH Wan and P-Y Lee
2008 Nature Publishing Group All rights reservedEye (2008) 22, 666-670,-0001,():
-1年11月30日
Purpose To investigate the comparative penetration of 0.3% levofloxacin eye drops into the aqueous humour between cataract patients with or without (control) thin-wall filtering blebs. Methods One drop of 0.3% levofloxacin was administered to the eyes at 30-min intervals for 3.5 h before phacoemulcification for both groups. Aqueous humour samples (0.1-0.2 ml) were aspirated during surgery. The concentration of levofloxacin in the aqueous humour was determined by high-performance liquid chromatography. The Student's t-test, Pearson correlation, and v2 test were used to compare the data of the two groups. A Po0.05 was required for results to be considered statistically significant. Results The levofloxacin concentration in the aqueous humour was significantly increased (P00.0001) in the bleb (meanþSD: 3.772.3 lg/ml) vs control group (0.470.2 lg/ml). Intraocular pressure and the bleb area were not correlated with levofloxacin concentration. Conclusion The presence of thin-wall filtering blebs increases intraocular penetration of topically administered levofloxacin. Eye (2008) 22, 666-670; doi:10.1038/sj.eye.6702712; published online 2 March 2007
thin-wall filtering bleb, levofloxacin, intraocular penetration, aqueous humour, trabeculectomy
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