Integrated Bioinformatics Analysis of DNA Methylation Biomarkers in Thyroid Cancer Based on TCGA Database.

Previous studies have reported a cluster of aberrant promoter methylation changes associated with silencing of tumor suppressor genes in thyroid cancer (TC), but these results of individual genes are far from enough. In this work, we aimed to investigate the onset and pattern of methylation changes during the progression of TC by informatics analysis. We downloaded the DNA methylation and RNA sequencing datasets from The Cancer Genome Atlas focusing on TC. Abnormally methylated differentially expressed genes (DEGs) were sorted and pathways were analyzed. The KEGG and GO were then used to perform enrichment and functional analysis of identified pathways and genes. Gene-drug interaction network and human protein atlas were applied to obtain feature DNA methylation biomarkers. In total, we identified 2170 methylation-driven DEGs, including 1054 hypermethylatedlow-expression DEGs and 1116 hypomethylated-high-expression DEGs at the screening step. Further analysis screened total of eight feature DNA methylation biomarkers (RXRG, MET, PDGFRA, FCGR3A, VEGFA, CSF1R, FCGR1A and C1QA). Pathway analysis showed that aberrantly methylated DEGs mainly associated with transcriptional misregulation in cancer, MAPK signaling, and intrinsic apoptotic signaling in TC. Taken together, we have identified novel aberrantly methylated genes and pathways linked to TC, which might serve as novel biomarkers for precision diagnosis and disease treatment.

The association of maternal diabetes with attention deficit and hyperactivity disorder in offspring: a meta-analysis.

OBJECTIVE: Recent controversial evidence suggests that maternal diabetes may increase the risk of attention deficit and hyperactivity disorder (ADHD) in offspring. To examine this potential association, a systematic literature search and meta-analysis was performed. METHODS: OR or risk ratio (RR) from each study was obtained and combined for evaluating the risk. Six cohort studies and three case-control studies were included in the present study. RESULTS: The meta-analysis of the highly heterogeneous case-control studies did not find significant association between maternal diabetes and ADHD risk (OR: 1.20, 95% CI: 0.96-1.49). The combining of the cohort studies demonstrated that offspring of diabetic mothers were at higher risk of ADHD (RR: 1.40, 95% CI: 1.27-1.54); however, publication bias was identified. When exposure was specified as gestational diabetes mellitus (GDM), GDM exposure increased the risk of ADHD for children by 164% (95% CI: 1.25-5.56) in a Caucasian population. Neither heterogeneity nor publication bias was detected. CONCLUSION: Maternal diabetes, especially GDM, is probably a risk factor for ADHD in the Caucasian population. More studies based on large sample size and different ethnicities are needed to confirm this association.

Monocular-Vision-Based Autonomous Hovering for a Miniature Flying Ball.

This paper presents a method for detecting and controlling the autonomous hovering of a miniature flying ball (MFB) based on monocular vision. A camera is employed to estimate the three-dimensional position of the vehicle relative to the ground without auxiliary sensors, such as inertial measurement units (IMUs). An image of the ground captured by the camera mounted directly under the miniature flying ball is set as a reference. The position variations between the subsequent frames and the reference image are calculated by comparing their correspondence points. The Kalman filter is used to predict the position of the miniature flying ball to handle situations, such as a lost or wrong frame. Finally, a PID controller is designed, and the performance of the entire system is tested experimentally. The results show that the proposed method can keep the aircraft in a stable hover.

[Features of vitreomacular traction syndrome assessed with three-dimensional spectral-domain optical coherence tomography].

OBJECTIVE: To describe features of vitreomacular traction syndrome (VMT) on three-dimensional (3D) spectral-domain optical coherence tomography (SD OCT). METHODS: Eighteen eyes of 18 patients with VMT were diagnosed by SD OCT. SD OCT images were obtained and retrospectively analyzed. These VMT cases were defined as focal type or broad type by the region of the vitreous attachment to the macula. The relationship between the logMAR best corrected visual acuity (BCVA) and the retinal thickness of macular fovea was evaluated by linear regression analysis. RESULTS: SD OCT provided detailed 3D images of VMT and revealed information about the extent of vitreomacular traction. Focal VMT was seen in 14 eyes. Broad VMT was seen in four eyes. Eight cases had concurrent epiretinal membrane in the areas surrounding the fovea. Two cases had concurrent full thickness macular hole and two cases had concurrent lamellar macular hole. LogMAR BCVA correlated with the retinal thickness of macular fovea (r = 0.616, P = 0.007, linear regression analysis). CONCLUSIONS: SD OCT allows good visualization of the architectural morphology of the vitreous and retina in vitreomacular traction syndrome. It is useful and irreplaceable for the diagnosis and follow-up of VMT.

Choroidal folds in acute Vogt-Koyanagi-Harada disease.

PURPOSE: To shed light on the clinical significance of choroidal folds (CFs) in acute Vogt-Koyanagi-Harada disease (VKH). METHODS: Twenty-three acute uveitic VKH patients diagnosed between October 2001 and January 2008 were reviewed retrospectively. RESULTS: Twelve (52%) patients had CFs; for patients with CFs, more had poor initial visual acuity (

[Clinical manifestation and follow-up of melanocytoma of the optic disc].

OBJECTIVE: To investigate the clinical manifestation and follow-up of melanocytoma of the optic disc. METHODS: Retrospective case series study was taken to study the clinical data of the cases with melanocytoma of the optic disc at Peking Union Medical College Hospital from 1978 to 2007. The examination included direct and indirect ophthalmoscopy, fundus photography, fundus fluorescein angiography (FFA), fundus indocyanine green angiography (ICGA), optical coherence tomography (OCT) and B-scan. The clinical manifestation and the outcome in follow-up period were analyzed. RESULTS: Ten cases aged 31-58 years (mean 43 years) were included in this study. Among them, 9 cases were male, 1 case was female. All cases were unilateral involved, 5 cases were right eye, 5 cases were left eye. The distribution of the visual acuity was follows: light perception in 2 eyes, 20/200 in one eye, 20/20 or above in 7 eyes. The tumor mass at the optic disc with extensive serous detachment of retina was detected on B-scan in one eye. The benign melanocytoma was diagnosed by vitreous fine needle biopsy for this eye. In other case, the tumor was found to be enlarged, visual field defect deteriorated, pigment granules appeared in the vitreous adjacent to the tumor during on year follow-up period. On the patient request, enucleation was performed to rule out the malignancy of the tumor. Pathologic study showed that the tumor cells were active, but benign state. The tumor size and visual acuity in other eight eyes remained stable in the follow-up period with one to 18 years (mean 3.5 years). On FFA and ICGA, bilateral choroidal nevi were found in one eye. CONCLUSIONS: Melanocytoma of the optic disc is a benign tumor that rarely causes visual impairment. However, visual acuity may be impaired due to enlargement of the tumor or necrosis in tumor. It is important to follow-up every case with melanocytoma of the optic disc as long as possible.

[Follow-up and management of Coats disease diagnosed in childhood].

OBJECTIVE: To investigate retrospectively the clinical manifestation and the final visual prognosis through a long-term fellow-up study. METHODS: It was retrospective case series study. Twenty four patients (26 eyes) were diagnosed with Coats disease from 1962 through 2006 at the Department of Ophthalmology, Peking Union Medical Hospital, Chinese Academy of Medical Sciences. Age, visual acuity, time of initial visit, method of treatment and the condition of eye fundus for each patient were documented. The time of follow-up ranged from 1-44 years, averaged 5 years. RESULTS: Age of the patients at initial visit ranged between 1 to 18 years old, 7 years on average. Eighteen patients (75%) were male and 6 were female (25%). Twenty two cases were unilateral and only 2 female patients were bilateral. In 26 eyes, 7 eyes exhibited capillary irregular dilatation, miliary aneurysms and nonperfusion area on fluorescein angiography located at peripheral fundus; 15 eyes were complicated with exudative retinal detachment. Four eyes reached end stage with no light perception or only finger count. Laser photocoagulation was performed in 21 eyes. In 10 eyes, retinal exudates and hemorrhages were absorbed with improvement of visual acuity. Ten eyes with extensive retinal detachment including macula underwent closed vitrectomy, the best visual acuity was 0.1 after surgery. CONCLUSIONS: The onset of Coats disease is in early young childhood. Abnormal vascular lesions and military aneurysms appeared at peripheral fundus with early retinal exudation involving the macula. Early treatment with laser coagulation could obtain good visual prognosis. The supplement treatment is required for new lesions occurring during the long- term follow-up period.

[Long-term follow-up and management of choroidal osteoma].

OBJECTIVE: To report the clinical characteristics, long-term follow-up and management of choroidal osteoma. METHODS: Eighteen eyes of 12 cases (5 male and 7 female) of choroidal osteoma were studied. Best corrected vision, intraocular pressure, perimetry, anterior segment and eye fundus were examined routinely. Special tests included phytochrome of eye fundus, fluorescein angiography and/or indocyanine green angiography; B-ultrasonogram, CT, perimetry and electrophysiology. (1) Eight eyes of 6 cases treated with vitamins and anti-inflammatory drug and followed-up periodically for 1-26 years (median 2.5 years). (2) Four eyes of 2 cases were treated with Krypton laser photocoagulation, 2 of them were superimposed with transpupillary thermotherapy (TTT). (3) TTT was given primarily for 6 eyes of 4 cases with infrared dione laser; the spot size was 3 mm, 1-5 spots were conducted conjunctly to cover the tumor surface. Power was 800-1200 mw at 60-90 seconds. The procedure was completed in 1-3 recessions with an interval of 4-6 weeks. RESULTS: (1) In the medical treatment group, gradual growth of the tumor with pseudopodium along the margin was disclosed. One eye showed spontaneously regression during the long-term follow-up. (2) Laser photocoagulation was effective for 2 eyes, but residual flat serous detachment around the optic disc persisted in another 2 eyes and subsided with TTT. (3) Choroidal osteoma complicated with CNV treated primarily with TTT, prominent improvement was demonstrated. CONCLUSIONS: Choroidal osteoma grows gradually in the natural course and shows pseudopodial margin. Laser photocoagulation was effective for certain cases. TTT is a method of choice either used primarily or supplementary after laser photocoagulation, it is recommended for cases complicated with CNV.

[Transpupillary thermotherapy for circumscribed choroidal hemangioma].

OBJECTIVE: To evaluate the efficacy of transpupillary thermotherapy (TTT) on circumscribed choroidal hemangioma. METHODS: Ten eyes of 10 cases with circumscribed choroidal hemangioma (age 16-48, average 34.4) were included in the present study. Six cases had previous green laser (4 argon and 2 krypton) photocoagulation, TTT as a primary treatment was used for other 4 cases without previous laser application. Fluorescein angiography, visual acuity, anterior segment and fundus examination, perimetry test, FFA/ICGA and ultrasonography were performed in all patients before the treatment. One to five infra red diode laser spots (810 nm with power of 800-1200 mW, diameter of 3 mm) were delivered on the surface of tumor with 60 seconds exposure, additional 10-20 seconds exposure was used in some cases. Second treatment was given 1-3 month later if there was active leakage demonstrated by fluorescein angiography. The followed-up period was 6-36 months (averaged 14.5 month). RESULTS: After transpupillary thermotherapy, 9 eyes (90%) showed partial regression of the tumor. Average visual acuity was 0.25 and 0.6 before and after TTT, respectively. Six patients showed improvement of vision acuity, but vision acuity in 4 patients with cystic macular degeneration remained unchanged. No recurrences were observed within follow-up averaged 14.5 months. Transpupillary thermotherapy did not associate with any significant complications. CONCLUSION: Transpupillary thermotherapy is effective to treat circumscribed hemangioma of choroid either as a primary treatment or supplementary therapy to previous laser photocoagulation.

[Cytomegalovirus retinitis associated with Acquired immunodeficiency syndrome].

OBJECTIVE: To investigate the fundus characteristics, systemic features and therapeutic outcomes of cytomegalovirus (CMV) retinitis associated with acquired immunodeficiency syndrome (AIDS). METHODS: Fundus features, visual acuity, fundus fluorescence angiography (FFA) and CD4(+)T-lymphocyte counts of 15 eyes (8 patients) of CMV retinitis associated with AIDS were analyzed. The time of average follow-up was 16 months. Intravitreal injection of ganciclovir (400 microg) was performed in 4 eyes (2 patients). RESULTS: In the initial examination, visual acuity of the patients was as following: < or = 0.2, 10 eyes (66.7%); no light perception (NLP) (2 eyes); light perception (LP) (2 eyes); 0.04-0.2, 6 eyes; > or = 1.0, 3 eyes (20.0%) and 0.8 or 0.9 each for 1 eye (13.3%). The fundus manifestation includes: the retinal vasculitis; dense, full-thickness, yellow-white lesions along vascular distribution, and hemorrhage on the retinal surface; granular with irregular border featured as "cheese and ketchup retinitis" was revealed in 12 eyes; the vitreous was clear or light opaque. Late stage of the retinopathy was demonstrated in 2 eyes characterized as grayish atrophic retina, vessel-sclerotic and attenuated, retinal pigment epithelium (RPE) atrophy, prominent choroid vasculature, and optic nerve atrophy. Retinal detachment was found in 1 eye. CD4(+)T-lymphocytes counts in peripheral blood were between 0 approximately 36/mm(3), average (15.0 +/- 12.9) mm(3). Visual acuity improved, fundus lesions disappeared observably and hemorrhage was absorbed in the 4 eyes after intravitreal injection of ganciclovir. CONCLUSIONS: CMV retinitis is the severest and the most common intraocular complication in patients with AIDS. For the patients with yellow-white retinal lesions, hemorrhage and retinal vasculitis of undefined cause, the antibody of serum anti-human immunodeficiency virus (HIV) should be screened. Routing eye examination should be performed if the serological test of HIV is positive.

[Krypton laser photocoagulation at low power setting for age-related macular degeneration complicated with subfoveal choroidal neovascularization].

OBJECTIVE: To evaluate the efficacy of krypton laser photocoagulation for treatment of age-related macular degeneration (AMD) complicated with mainly subfoveal classic choroidal neovascularization (CNV). METHODS: Seventeen eyes of 17 cases, aged 50 - 74 years (averaged 60.8 years) with mainly subfoveal classic choroidal neovascularization were treated with krypton laser at lower power setting. The treatment was completed in one session. Another course of treatment was given 4 weeks later if there was active leakage demonstrated at the CNV area. Visual acuity, anterior segment and fundus examination, perimetry test, fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were performed before and after treatment. The follow-up period was 3.5 years on average (1 - 8 years). RESULTS: There was no immediately decrease of visual acuity after treatment. All treated eyes showed absorption of hemorrhages and/or exudates and diminished leakages. Visual acuity was stable in 8 eyes; improved in 6 eyes (>/= 2 lines), and decreased in 3 eyes (

[Natural course and prognosis of visual acuity in patients of age-related macular degeneration with occult choroidal neovascularization].

OBJECTIVE: To investigate the natural course and the final visual acuity in patients of age-related macular degeneration with choroidal neovascularization. METHODS: Thirty five eyes of 29 patients diagnosed as AMD with occult choroidal neovascularization were studied. The eyes which had laser, radiation therapy or surgical treatment were excluded. Visual acuity, fundus examination, fluorescent angiography (FFA) and perimetry test were performed at the first time visit and 5 years following-up at an interval of 1 to 3 months. The average following-up period of time was 8 years (range from 5 to 16 years) which started in 1985 and ended in 2001. RESULTS: Initial visual acuity 0.1 or less was shown in 10 eyes (28.5%, only hands movement can be seen in 4 of 10 eyes), 23 eyes (65.7%) with visual acuity of 0.1 or less (14 eyes with vision acuity of hands movement) on the last visit. 7 of 35 eyes, the final visual acuity improved more than 2 lines, 12 eyes remained the same and 16 eyes had been lost vision more than two lines. At the baseline examination, 25 eyes had macular hemorrhages and 4 eyes had vitreous hemorrhages. The fundus hemorrhages occurred repeatedly 1 to 4 times in 23 eyes during following-up, the macular hemorrhages was detected in 7 eyes at the last visit. At the initial fundus examination, fibrotic membranes were found in 7 eyes; all 35 eyes had disc form scarring with various size in most recent following-up. CONCLUSION: The natural course of Age-related macular degeneration with choroidal neovascularization is prolonged and the final visual prognosis was poor especially in the cases with recurrent macular hemorrhages.