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1.
Int J Med Sci ; 20(4): 542-550, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37057214

RESUMO

This study aimed to investigate the capsule-epithelium-fibre unit ultrastructure of the human lens, particularly the interfaces of the epithelium with the capsule and the epithelium with the fibre cell. A total of 12 lenses from donor humans who died of trauma without systemic and ocular diseases were investigated by transmission electron microscopy (TEM), combined with immunofluorescence staining for localising certain specific proteins. Some of the results were further studied in the anterior lens capsules of cataract patients. Our results revealed capsule protrusion into the epithelium in some areas and potential processing of capsule components. The young elongating fibre cells directly adjacent to the epithelium with a high stain density strongly expressed CD24. Numerous extracellular vesicles could be seen in the space between human lens epithelial cells (HLECs) and between HLECs and the capsule. Mitophagy and autophagy were also observed in the HLECs. Our research may be beneficial in better understanding the function of the human lens.


Assuntos
Catarata , Cristalino , Humanos , Cristalino/ultraestrutura , Epitélio/ultraestrutura , Células Epiteliais , Microscopia Eletrônica de Transmissão
2.
Nature ; 506(7488): 376-81, 2014 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-24390342

RESUMO

A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ∼10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2 - 4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation, cis-acting expression quantitative trait loci and pathway analyses--as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes--to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Descoberta de Drogas , Predisposição Genética para Doença/genética , Terapia de Alvo Molecular , Alelos , Animais , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Povo Asiático/genética , Estudos de Casos e Controles , Biologia Computacional , Reposicionamento de Medicamentos , Feminino , Estudo de Associação Genômica Ampla , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/metabolismo , Humanos , Masculino , Camundongos , Camundongos Knockout , Polimorfismo de Nucleotídeo Único/genética , População Branca/genética
3.
Immunol Cell Biol ; 94(3): 293-305, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26467610

RESUMO

FOXP3+ regulatory T (Treg) cells are indispensable for immune homeostasis, but their study in humans is complicated by heterogeneity within Treg, the difficulty in purifying Tregs using surface marker expression (e.g. CD25) and the transient expression of FOXP3 by activated effector cells. Here, we report that expression of CD39 and CD45RO distinguishes three sub-populations within human CD4(+)CD25(hi) T cells. Initial phenotypic and functional analysis demonstrated that CD4(+)CD25(hi)CD39(+)CD45RO(+) cells had properties consistent with effector Treg, CD4(+)CD25(hi)CD39(-)CD45RO(-) cells were naïve Treg and CD4(+)CD25(hi)CD39(-)CD45RO(+) cells were predominantly non-Treg with effector T-cell function. Differences in these two newly identified Treg subsets were corroborated by studies of gene expression and TCR analysis. To apply this approach, we studied these two newly identified Treg subsets in ankylosing spondylitis, and showed impairment in both effector and naïve Treg. This work highlights the importance of discriminating Treg subsets to enable proper comparisons of immune regulatory capacity in healthy individuals and those with inflammatory disease.


Assuntos
Expressão Gênica , Fenótipo , Receptores de Antígenos de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismo , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Superfície/metabolismo , Biomarcadores , Citocinas/metabolismo , Perfilação da Expressão Gênica , Humanos , Imunomodulação , Imunofenotipagem , Ativação Linfocitária/imunologia , Camundongos , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Espondilite Anquilosante/genética , Espondilite Anquilosante/imunologia , Espondilite Anquilosante/metabolismo , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia
4.
Int J Ophthalmol ; 17(6): 1086-1093, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895689

RESUMO

AIM: To evaluate the effect of low-degree astigmatism on objective visual quality through the Optical Quality Analysis System (OQAS). METHODS: This study enrolled 46 participants (aged 23 to 30y, 90 eyes) with normal or corrected-to-normal vision. The cylindrical lenses (0, 0.5, 0.75, 1.0, and 1.25 D) were placed at the axial direction (180°, 45°, 90°, and 135°) in front of the eyes with the best correction to form 16 types of regular low-degree astigmatism. OQAS was used to detect the objective visual quality, recorded as the objective scattering index (OSI), OQAS values at contrasts of 100%, 20%, and 9% predictive visual acuity (OV100%, OV20%, and OV9%), modulation transfer function cut-off (MTFcut-off) and Strehl ratio (SR). The mixed effect linear model was used to compare objective visual quality differences between groups and examine associations between astigmatic magnitude and objective visual quality parameters. RESULTS: Apparent negative relationships between the magnitude of low astigmatism and objective visual quality were observed. The increase of OSI per degree of astigmatism at 180°, 45°, 90°, and 135° axis were 0.38 (95%CI: 0.35, 0.42), 0.50 (95%CI: 0.46, 0.53), 0.49 (95%CI: 0.45, 0.54) and 0.37 (95%CI: 0.34, 0.41), respectively. The decrease of MTFcut-off per degree of astigmatism at 180°, 45°, 90°, and 135° axis were -10.30 (95%CI: -11.43, -9.16), -12.73 (95%CI: -13.62, -11.86), -12.75 (95%CI: -13.79, -11.70), and -9.97 (95%CI: -10.92, -9.03), respectively. At the same astigmatism degree, OSI at 45° and 90° axis were higher than that at 0° and 135° axis, while MTFcut-off were lower. CONCLUSION: Low astigmatism of only 0.50 D can significantly reduce the objective visual quality.

5.
Am J Physiol Lung Cell Mol Physiol ; 305(4): L312-21, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23771884

RESUMO

Bone morphogenetic protein type II receptor (BMPR-II) mutations are responsible for over 70% of cases of heritable pulmonary arterial hypertension (PAH). Loss of BMP signaling promotes pulmonary vascular remodeling via modulation of pulmonary artery smooth muscle cell (PASMC) proliferation. Id proteins (Id1-4) are major downstream transcriptional targets of BMP signaling. However, the impact of BMPR-II mutation on the expression of the range of Id proteins and the contribution of individual Id proteins to abnormal PASMC function remain unclear. Human PASMCs were used to determine the expression of Id proteins (Id1-4) by real-time PCR and immunoblotting. The BMP responses in control cells were compared with PASMCs harboring BMPR-II mutations and cells in which BMPR-II was knocked down by siRNA transfection. Id3 expression in pulmonary vessels was also investigated in BMPR-II mutant mice and in patients with heritable PAH. BMP4 and BMP6, but not BMP9, induced mRNA expression of Id1, Id2, and Id3. The BMP-stimulated induction of Id1 and Id3 was markedly reduced in BMPR-II mutant PASMCs and in control PASMCs following siRNA silencing of BMPR-II. Pulmonary arteries in BMPR-II mutant mice and patients with heritable PAH demonstrated reduced levels of Id3 compared with control subjects. Lentiviral overexpression of Id3 reduced cell cycle progression and inhibited proliferation of PASMCs. Lipopolysaccharide further reduced Id3 expression in mutant PASMCs. In conclusion, Id proteins, and particularly Id1 and Id3, are critical downstream effectors of BMP signaling in PASMCs. Loss of BMPR-II function reduces the induction of Id genes in PASMCs, Id1, and Id3 regulate the proliferation of PASMCs via cell cycle inhibition, an effect that may be exacerbated by inflammatory stimuli.


Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas Inibidoras de Diferenciação/metabolismo , Miócitos de Músculo Liso/metabolismo , Artéria Pulmonar/patologia , Animais , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/deficiência , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/metabolismo , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Hipertensão Pulmonar Primária Familiar , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/patologia , Proteínas Inibidoras de Diferenciação/genética , Lipopolissacarídeos/farmacologia , Pulmão/patologia , Camundongos , Camundongos Mutantes , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
6.
Adv Ther ; 39(3): 1393-1402, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35106691

RESUMO

OBJECTIVES: To analyze the history of biologics usage in patients with ankylosing spondylitis (AS) in China and to evaluate the impact of drug reduction and withdrawal on disease activity. METHODS: Drug administration intervals and disease activity indexes in patients with AS who regularly used etanercept (ETN) biosimilars for more than 1 year and those who withdrew the drugs during the same period in a single center were analyzed retrospectively. RESULTS: A total of 108 patients with AS who used ETN biosimilars for more than a year were recruited in this study for analysis. (1) Overall, 98.1% patients with AS increased the intervals between drug administrations, averaging from 4.57 ± 0.15 days during 0-3 months to 8.53 ± 0.43 days during 3-6 months, and to 10.49 ± 0.39 days during 6-12 months. Compared with the baseline parameters, after 3-month and 12-month treatments disease activities were improved significantly, including Patient Global Assessment (PTGA), overall back pain, nocturnal pain, fatigue, Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Functional Index (BASFI). (2) Only 59.3% used ETN biosimilars with full dose (3.5 days' interval) in the first 3 months. At baseline, disease activities of these patients were higher than those with reduced dose (5.9 days' interval). However, at 12 months of drug administration there was no significant difference in the overall length of drug administration intervals and disease activities between the two groups. (3) Twenty patients with low disease activity (LDA) discontinued therapy spontaneously; after 3 months, 55% of them experienced disease recurrence (∆ASDAS ≥ 0.9). CONCLUSION: Spontaneous dose reduction was a common phenomenon among patients with AS in China, which becomes more notable with increasing relief of symptoms. Most patients could maintain an LDA state after dose reduction. Compared with dose reduction, ETN biosimilar withdrawal was more likely to induce disease recurrence. Therefore, disease activity-guided individualized stepwise tapering may become one of the feasible therapeutic strategies for AS in the future.


Assuntos
Medicamentos Biossimilares , Espondilite Anquilosante , Medicamentos Biossimilares/uso terapêutico , Etanercepte/uso terapêutico , Humanos , Estudos Retrospectivos , Índice de Gravidade de Doença , Espondilite Anquilosante/tratamento farmacológico
7.
Ann Transl Med ; 9(2): 144, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33569446

RESUMO

BACKGROUND: To compare the visual performance of MF30 asymmetric refractive multifocal intraocular lenses (MIOLs) with ZMB00 all optic zone diffractive MIOLs. METHODS: This is a prospective study. Patients that underwent phacoemulsification were divided into two groups according to the type of MIOLs used: 35 patients were implanted with asymmetric refractive MIOLs and 35 patients with all optic zone diffractive MIOLs. Visual acuity (VA), refraction, defocus curves, objective optical quality, and a questionnaire evaluating quality of life were measured at 3 months postoperatively. RESULTS: There were no significant differences between the two groups in uncorrected distance visual acuity (UDVA), uncorrected near visual acuity (UNVA), best-corrected distance visual acuity (BCDVA), or distance-corrected near visual acuity (DCNVA). However, the uncorrected intermediate VA was 0.24±0.10 in the refractive group and 0.31±0.13 in the diffractive group (P<0.05), and the distance-corrected intermediate VA was 0.22±0.09 in the refractive group and 0.31±0.14 in the diffractive group (P<0.05). Defocus curves showed two peaks of maximum vision in both groups. However, the curve between the two peaks in the refractive group was smoother than that of the diffractive group. The modulated transfer function cut-off frequency was 22.74±12.29 c/d in the refractive group and 30.50±10.04 c/d in the diffractive group (P<0.05). The Optical Quality Analysis System (OQAS) values 100% (OV100%) was 0.75±0.41 in the refractive group and 1.02±0.34 in the diffractive group (P<0.05), while the OV20% was 0.52±0.34 in the refractive group and 0.71±0.25 in the diffractive group (P<0.05). There was no significant difference between the two groups in overall satisfaction, spectacle independence ratio, or visual interference phenomenon. CONCLUSIONS: Both MIOLs achieve good VA at distance and near vision. Oculentis MF30 showed better intermediate VA, and Tecnis ZMB00 appears to have better objective visual quality. TRIAL REGISTRATION: NCT02234635 (http://www.clinicaltrials.gov).

8.
Pain Ther ; 10(2): 1467-1479, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34482533

RESUMO

INTRODUCTION: Pain in ankylosing spondylitis is currently considered an inflammatory pain (IP). However, it was found that some patients still had the sensation of pain even without inflammation. Our study was to investigate the prevalence and characteristics of neuropathic pain (NeP) in Chinese Han ankylosing spondylitis (AS) patients. METHODS: The study consisted of three parts. Firstly, we assessed the prevalence and clinical data of NeP in 182 AS patients. Secondly, we evaluated pain improvement after etanercept therapy in 63 patients. Finally, serum neurotransmitters were measured for 20 AS patients and ten healthy controls (HC). RESULTS: Out of 182 AS patients, our study showed that 14 patients (7.70%) had likely NeP and 55 (30.21%) had uncertain NeP. There were significant differences among the three groups with respect to nocturnal pain (NP), peripheral pain (PP), total back pain (TBP), BASDAI, ASDAS-CRP, HAD-A, HAD-D, and BASDAI-fatigue except fort CRP concentrations. Principal component analysis (PCA) of AS pain revealed that the weight of NeP was greater than PP in the first principal component (0.703 vs. 0.639). Structural equation modeling (SEM) revealed that NeP altered disease activity (ß = 0.62, P < 0.001), which influenced psychological status (ß = 0.42, P < 0.001). Of 63 patients who used etanercept for 3 months, significant improvement was found in NP, TBP, and PP (all P < 0.0001) but not in PDQ (10.60 ± 6.85 vs. 9.98 ± 6.40, P = 0.0671). Serum norepinephrine concentrations in patients with PDQ > 19 were higher than those in patients with PDQ ≤ 19 and HC. CONCLUSIONS: We conclude that NeP contributes to pain in AS patients.

9.
Int J Ophthalmol ; 14(12): 1903-1908, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926206

RESUMO

AIM: To investigate the safety and efficacy of sticky silicone oil (SSO) removal using a 22-gauge vein detained needle and inner limiting membrane (ILM) wrap-and-peel technique. METHODS: This retrospective consecutive case series reviewed the records of patients with a history of retinal detachment who had received silicone oil and perfluorocarbon liquid (PFCL) as intraocular tamponades. Patients were included in the analysis if they exhibited SSO remnants during silicone oil removal. The aspiration of most of the SSO remnants was performed by a 22-gauge vein detained needle. The small amounts of droplets adhered to the macula and epi-macular membrane were subsequently removed by the ILM warp-and-peel technique. The anatomical and functional outcomes, and postoperative complications were recorded. In vitro experiments were performed to simulate the formation of SSO remnants in four groups. RESULTS: Of 711 patients who underwent silicone oil removal during the study period, 9 patients exhibited SSO remnants and underwent follow-up for at least 3mo. Seven eyes (78%) underwent the ILM wrap-and-peel technique to completely remove small droplets of SSO that were glued to the macula and epi-macular membrane. No obvious complications occurred. Postoperative optical coherence tomography revealed normal retinal structure in all patients. In vitro analyses showed that balanced salt solution and prolonged vibration (for 1wk) had the strongest effects on silicone oil and PFCL compound opacities. CONCLUSION: SSO remnants could be removed in an intact manner and without complications, using a vein detained needle-assisted and ILM wrap-and-peel technique. The findings suggest that PFCL and infusion fluid should be completely removed before silicone oil injection to prevent SSO formation.

10.
Zhonghua Yan Ke Za Zhi ; 46(8): 725-30, 2010 Aug.
Artigo em Zh | MEDLINE | ID: mdl-21054998

RESUMO

OBJECTIVE: The guinea pig becomes an important model for studies on myopia, but little is known about its visual performance. In this study, grating acuity was measured using a custom-built automated device to track optomotor responses. METHODS: To record head nystagmus, guinea pigs were individually placed in the center of a rotating drum of 130 cm diameter. The drum was covered inside with square wave gratings of adjustable fundamental spatial frequencies and contrast. The turning movements of the head were tracked using custom-written video software that detected two little white spots painted on a small black piece of cardboard that was attached to the guinea pig's head. Angular head speed was determined from the positions of the two white spots with respect to each other over time, and the ratio of angular head speed to drum speed was determined (the "gain"). In 11 guinea pigs of the same age, but with different refractive states (+9.7 to -15.0 D), responses to spatial frequencies of 0.6 and 2.4 cyc/deg were tested. Furthermore, 17 guinea pigs were tested which had similar refractive states but were different in age (1 to 3 months old). Finally, the effects of different grating contrasts were studied (25%, 50% and 100% contrast respectively) and the effects of different stripe luminances (10, 30, and 350 cd/m(2) respectively). RESULTS: The optomotor response could be used to measure vision in one eye only even if both eyes opened. The optomotor gain was affected by refractive error. Younger animals (one month old) had lower optomotor gain than older ones (0.61 ± 0.2 in one-month, 0.77 ± 0.13 in two-month and 0.80 ± 0.11 in three-month old). For a spatial frequency of 0.6 cyc/deg, the effects of stripe contrast were tested in two months old guinea pigs. At an average stripe luminance of 30 cd/m(2), the optomotor gain dropped from 0.95 ± 0.20 at maximal contrast, to 0.94 ± 0.16 at 50% contrast, and 0.70 ± 0.10 at 25% contrast. At three different luminances, gains were 0.81 ± 0.25 (10 cd/m(2)), 0.95 ± 0.20 (30 cd/m(2)), and 0.80 ± 0.09 (350 cd/m(2)), measured with gratings of 100% contrast, respectively. CONCLUSIONS: Myopic guinea pigs have reduced grating acuity compared to hyperopic ones. The optomotor gain increases with age. For a given grating contrast, the highest optomotor gains are obtained at the highest luminance of 30 cd/m(2). In summary, spatial vision in guinea pig declines with the magnitude of myopia, and increases with luminance and age.


Assuntos
Miopia/fisiopatologia , Optometria/instrumentação , Optometria/métodos , Animais , Desenho de Equipamento , Cobaias , Refração Ocular , Acuidade Visual
11.
Materials (Basel) ; 13(12)2020 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-32545854

RESUMO

The deformation behavior and microstructural evolution of fine-grained 2050 alloys at elevated temperatures and slow strain rates were investigated. The results showed that significant dynamic anisotropic grain growth occurred at the primary stage of deformation. Insignificant dislocation activity, particle-free zones, and the complete progress of grain neighbor switching based on diffusion creep were observed during superplastic deformation. Quantitative calculation showed that diffusion creep was the dominant mechanism in the superplastic deformation process, and that grain boundary sliding was involved as a coordination mechanism. Surface studies indicated that the diffusional transport of materials was accomplished mostly through the grain boundary, and that the effect of the bulk diffusion was not significant.

12.
Materials (Basel) ; 13(4)2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32092875

RESUMO

In this paper, the effect of trace Sn on the precipitation behavior and mechanical properties of Al-Mg-Si alloys with different Mg/Si ratios aged at 180 °C was investigated using hardness measurements, a room-temperature tensile test, transmission electron microscopy and differential scanning calorimetry. The results shown that Sn reduces the precipitation activation energy, increases the number density of ß″ precipitates, and then increased the aging hardenability and mechanical properties of the Al-Mg-Si alloy. However, the positive effect of Sn on the mechanical properties of the Al-Mg-Si alloy drops with the decrease of the Mg/Si ratio of the alloy.

13.
Materials (Basel) ; 13(15)2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32707847

RESUMO

The effect of different precipitate microstructures obtained by different heat treatments on fatigue behavior of 7020 aluminum alloy was investigated. The fine Guinier Preston I (GPI) zones in the under-aged alloy can be repeatedly sheared by dislocations produced in cyclic loading, making the fatigue crack initiate difficultly and fatigue crack path propagate tortuously. Fatigue strength and fatigue crack propagation resistance of the alloy with shearable precipitates are much higher than those of the alloy with unshearable precipitates. The peak-aged alloy with continuous grain boundary precipitate (GBP) and narrow precipitate free zone (PFZ) is prone to initiate fatigue cracks and reduce fatigue strength. With the growth of unshearable precipitates, the fatigue strength of the alloy firstly increases and then decreases. Precipitates with moderate size in the over-aged alloy improve the roughness-induced crack closure (RICC) effect. Soft matrix with appropriate width between the precipitates can promote the slip reversibility and relax the crack tip stress. The fatigue strength of the moderately over-aged alloy reaches to 122.1 MPa at 107 cycles of loading, and the fatigue crack growth rate (FCGR) is 35.6% slower than that of the peak-aged alloy at ΔK of 10 MPa·m1/2.

14.
Materials (Basel) ; 12(24)2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31842351

RESUMO

The microstructures and mechanical properties of friction stir welded (FSW) Al-Zn-Mg alloy plate under different travel speeds were investigated. Both the average grain sizes (AGSs) of the shoulder affected zone (SAZ), nugget zone (NZ), and the widths of thermo-mechanically affected zone (TMAZ) decreased with the increase of travel speed. Moreover, the AGSs of NZ are always about 60% of that of SAZ at different travel speeds. The fractions of high-angle grain boundaries (HAGBs) in the FSW joints reduce with the distance away from the stir zone (SZ). Furthermore, the initial η' strengthening precipitates in NZ and TMAZ dissolve and GP zones form during subsequent natural aging, so that the hardness is similar in the two zones. The precipitate evolution in the heat-affected zone (HAZ) at hardness minima are affected by travel speeds, which induce the hardness minima and ultimate tensile strength (UTS) of FSW joints and increase with the increase of travel speed, and a fracture tends to occur at hardness minima location of HAZ during tensile testing.

16.
J Ophthalmol ; 2018: 9250425, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30687549

RESUMO

PURPOSE: To report a new technique for sutureless intrascleral fixation of three-piece foldable intraocular lenses (IOLs) using 25-gauge trocars. METHODS: We performed this technique on patients with insufficient posterior capsule support. Seventeen eyes from 15 patients with aphakia, dislocated IOL, or subluxated crystalline lens undergoing posterior chamber sutureless implantation of an IOL were studied. The haptics of the IOL were externalized using two 25-gauge forceps. The haptics were bended back (hook-like) into the vitreous cavity through a scleral incision made by using a 25-gauge trocar. And, IOL tilt was determined by using a slit lamp and UBM, and complications were recorded. RESULTS: The IOLs were fixed with exact centration and axial stability. No wound leakage was reported even without the use of sutures. The mean best-corrected visual acuity (BCVA) was 0.82 logarithm of the minimum angle of resolution (logMAR) units preoperatively, and the mean BCVA was 0.44 logMAR units at the 6-month follow-up visit. No postoperative retinal detachment, endophthalmitis, IOL tilt or dislocation, or vitreous hemorrhage was noted. CONCLUSION: Sutureless intrascleral haptic-hook posterior chamber IOL implantation using 25-gauge trocars provides good IOL fixation with reliable wound closure without the use of sutures. This trial is registered with ChiCTR1800017436.

19.
Arthritis Rheumatol ; 66(5): 1121-32, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24782177

RESUMO

OBJECTIVE: To investigate differences in genetic risk factors for rheumatoid arthritis (RA) in Han Chinese as compared with Europeans. METHODS: A genome-wide association study was conducted in China with 952 patients and 943 controls, and 32 variants were followed up in 2,132 patients and 2,553 controls. A transpopulation meta-analysis with results from a large European RA study was also performed to compare the genetic architecture across the 2 ethnic remote populations. RESULTS: Three non-major histocompatibility complex (non-MHC) loci were identified at the genome-wide significance level, the effect sizes of which were larger in anti-citrullinated protein antibody (ACPA)-positive patients than in ACPA-negative patients. These included 2 novel variants, rs12617656, located in an intron of DPP4 (odds ratio [OR] 1.56, P = 1.6 × 10(-21) ), and rs12379034, located in the coding region of CDK5RAP2 (OR 1.49, P = 1.1 × 10(-16) ), as well as a variant at the known CCR6 locus, rs1854853 (OR 0.71, P = 6.5 × 10(-15) ). The analysis of ACPA-positive patients versus ACPA-negative patients revealed that rs12617656 at the DPP4 locus showed a strong interaction effect with ACPAs (P = 5.3 × 10(-18) ), and such an interaction was also observed for rs7748270 at the MHC locus (P = 5.9 × 10(-8) ). The transpopulation meta-analysis showed genome-wide overlap and enrichment in association signals across the 2 populations, as confirmed by prediction analysis. CONCLUSION: This study has expanded the list of alleles that confer risk of RA, provided new insight into the pathogenesis of RA, and added empirical evidence to the emerging polygenic nature of complex trait variation driven by common genetic variants.


Assuntos
Artrite Reumatoide/etnologia , Artrite Reumatoide/genética , Povo Asiático/genética , Dipeptidil Peptidase 4/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas do Tecido Nervoso/genética , Receptores CCR6/genética , População Branca/genética , Adulto , Alelos , Artrite Reumatoide/epidemiologia , Estudos de Casos e Controles , Proteínas de Ciclo Celular , China/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
20.
Invest Ophthalmol Vis Sci ; 50(3): 1013-9, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19029033

RESUMO

PURPOSE: To describe a wild-type guinea pig strain with an incidence of spontaneous axial myopia, minimal pupil responses, lack of accommodation, and apparently normal spatial vision. Such a strain is of interest because it may permit the exploration of defective emmetropization and mapping of the underlying quantitative trait loci. METHODS: Twenty-eight guinea pigs were selected from 220 animals based on binocular myopia (exceeding -1.50 diopter [D]) or anisometropia (difference between both eyes exceeding 10 D) at 4 weeks of age. Refractions and pupil responses were measured with eccentric infrared photoretinoscopy, corneal curvature by modified conventional keratometer, and axial lengths by A-scan ultrasonography once a week. Twenty-one guinea pigs were raised under a normal 12-hour light/12-hour dark cycle. From a sample of 18 anisometropic guinea pigs, 11 were raised under normal light cycle and 7 were raised in the dark to determine the extent to which visual input guides emmetropization. Spatial vision was tested in an automated optomotor drum. RESULTS: In 10 guinea pigs with myopia in both eyes, refractive errors ranged from -15.67 D to -1.50 D at 3 weeks with a high interocular correlation (R = 0.82); axial length and corneal curvature grew almost linearly over time. Strikingly, two patterns of recovery were observed in anisometropic guinea pigs: in 12 (67%) anisometropia persisted, and in 6 (33%) it declined over time. These ratios remained similar in dark-reared guinea pigs. Unlike published strains, all guinea pigs of this strain showed weak pupil responses and no signs of accommodation but up to 3 cyc/deg of spatial resolution. CONCLUSIONS: This strain of guinea pigs has spontaneous axial refractive errors that may be genetically or epigenetically determined. Interestingly, it differs from other published strains that show no refractive errors, vivid accommodation, or pupil responses.


Assuntos
Acomodação Ocular/fisiologia , Modelos Animais de Doenças , Miopia/genética , Distúrbios Pupilares/genética , Animais , Anisometropia/genética , Anisometropia/fisiopatologia , Córnea/patologia , Cobaias , Miopia/fisiopatologia , Distúrbios Pupilares/fisiopatologia , Refração Ocular/fisiologia , Retinoscopia , Acuidade Visual/fisiologia
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