RETINAL MICROVASCULAR CHANGES IN UVEAL MELANOMA FOLLOWING CONBERCEPT INJECTION AFTER PLAQUE RADIOTHERAPY AS DETECTED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To investigate macular microvascular characteristics imaged by optical coherence tomography angiography in patients with uveal melanoma following conbercept injections after plaque radiotherapy. METHODS: Prospective comparative analysis comprising 15 patients with uveal melanoma with conbercept injections and 30 patients without conbercept injections after plaque radiotherapy by optical coherence tomography angiography. The conbercept group received intravitreal conbercept injections at the time of plaque removal, 1 month, 3 months, 6 months , 9 months and 12 months after plaque removal (total, 6 injections). The control group had no intravitreal conbercept injection. RESULTS: After initiation of conbercept injections, superficial retinal vascular density in the whole image and parafoveal region were significantly higher at 6 months, whereas there was no significant difference at 9 months and 12 months. In analysis of variance analysis, superficial retinal vascular density in the whole image remained stable after conbercept injections (P = 0.069), whereas the superficial retinal vascular density decreased significantly after plaque radiotherapy in the control group (P = 0.011). In multivariable linear regression, a higher superficial retinal vascular density in the whole image region at 6 months was significantly associated with intravitreal conbercept injection (P = 0.018), wider tumor base (P = 0.026), and thinner tumor thickness (P = 0.04). CONCLUSION: Optical coherence tomography angiography can provide a quantitative evaluation of early retinal microvascular changes after radiotherapy. Intravitreal conbercept treatment could partly relieve the retinal vascular damage in response to radiation therapy at early stage in patients with uveal melanoma; however, it may not be able to provide long-term positive functional outcomes.

Microvascular retinal changes in pre-clinical diabetic retinopathy as detected by optical coherence tomographic angiography.

PURPOSE: To investigate microvascular abnormalities in diabetic patients without conventional clinical signs of diabetic retinopathy (DR). METHODS: In this cross-sectional observational cohort study, the study group included randomly chosen participants of a community-based cohort with diabetes type 2 without DR, and the control group consisted of non-diabetic individuals from a population-based study. All participants underwent optical coherence tomographic angiography (OCTA). RESULTS: Upon OCTA, 118 (40.4%) eyes of the study group (n = 292 eyes) showed microvascular abnormalities including foveal avascular zone erosion (95 (32.5%) eyes), non-perfusion areas in the superficial and deep retinal layers (39 (13.4%) eyes and 19 (6.5%) eyes, respectively), and microaneurysms in the superficial and deep retinal layers (22 (7.5%) eyes and 31 (10.6%) eyes, resp.). None of these abnormalities was detected in the control group (n = 80). The study group showed a lower vessel density in the superficial retinal vascular layer in all regions except for the foveal region (P < 0.001), and higher vessel density in the parafoveal region in the deep retinal vascular layer (P = 0.01). Higher diabetes prevalence was associated with lower superficial retinal vascular density (P = 0.005) in multivariable analysis. A lower radial peripapillary capillary flow density was correlated (regression coefficient r, 0.62) with higher fasting blood concentration of glucose (P < 0.001) in multivariable analysis. CONCLUSIONS: OCTA revealed microvascular abnormalities in 40% of eyes of diabetic patients without ophthalmoscopically detectable diabetic fundus changes in a community-based population. The early stage of DR may be re-defined upon OCTA.

Thickness of individual layers at the macula and associated factors: the Beijing Eye Study 2011.

BACKGROUND: Diagnosis and follow-up of retinal diseases may be improved if the thickness of the various retinal layers, in addition to the total retinal thickness, is taken into account. Here we measured the thickness of the macular retinal layers in a population-based study group to assess the normative values and their associations. METHODS: Using spectral-domain optical coherence tomographic images (Spectralis®, wavelength: 870 nm; Heidelberg Engineering Co, Heidelberg, Germany), we measured the thickness of the macular retinal layers in participants of the population-based Beijing Eye Study without ocular diseases and without systematic diseases, such as arterial hypertension, hyperlipidemia, diabetes mellitus, cardiovascular diseases, previous myocardial infarction, cerebral trauma and stroke. Segmentation and measurement of the retinal layers was performed automatically in each of the horizontal scans. RESULTS: The study included 384 subjects (mean age:60.0 ± 8.0 years). The mean thickness of the whole retina, outer plexiform layer, outer nuclear layer,retinal pigment epithelium, inner retinal layer and photoreceptor layer was 259.8 ± 18.9 µm, 19.4 ± 3.9 µm, 93.4 ± 9.6 µm, 17.6 ± 1.9 µm, 169.8 ± 18.6 µm, and 90.0 ± 4.2 µm, respectively. In multivariable analysis, the thickness of the foveola and of all retinal layers in the foveal, parafoveal and perifoveal region decreased with older age (all P < 0.05), except for the thickness of the parafoveal outer plexiform layer which increased with age. Men as compared to women had higher thickness measurements of the photoreceptor layer and outer nuclear layer in all areas, and of all layers between the retinal nerve fiber layer and inner nuclear layer in the parafoveal area (all P < 0.05). The associations between the macular retinal layers thickness and axial length were not consistent. The inner plexiform layer was thicker, and the ganglion cell layer and inner nuclear layer were thinner, in the temporal areas than in the nasal areas, CONCLUSIONS: The associations between decreasing thickness of most retinal layers with older age and the correlation of a higher thickness of some retinal layers with male gender may clinically be taken into account.

Ten-Year Progression of Myopic Maculopathy: The Beijing Eye Study 2001-2011.

PURPOSE: To investigate the progression pattern of myopic maculopathy and associated factors in a population-based study. DESIGN: Population-based longitudinal study. PARTICIPANTS: The Beijing Eye Study including 4439 participants in 2001 was repeated in 2011, with 2695 individuals (66.4%) being re-examined in 2011. METHODS: The study participants underwent detailed ophthalmic and general examinations. Using fundus photographs obtained in 2001 and 2011, we assessed the progression of myopic maculopathy in highly myopic eyes with a refractive error ≥-6 diopters in 2001. Myopic maculopathy was differentiated into tessellated fundus (category 1), diffuse chorioretinal atrophy (category 2), patchy chorioretinal atrophy (category 3), and macular atrophy (category 4), with lacquer cracks and choroidal neovascularization as additional plus signs. MAIN OUTCOME MEASURES: Progression pattern of myopic maculopathy. RESULTS: Of 110 highly myopic eyes (70 individuals) at baseline, 39 eyes (35.5%) showed progression observed in 15 of 79 eyes (19%) with tessellated fundus at baseline, in 17 of 24 eyes (71%) with diffuse chorioretinal atrophy, in all 6 eyes with patchy chorioretinal atrophy, and the 1 eye with macular atrophy. Lacquer cracks detected in 2 eyes in 2001 developed into a small patchy atrophy (1 eye) or widened during the follow-up (1 eye). Five eyes demonstrated new lacquer cracks. In binary regression analysis, progression of myopic maculopathy was associated with longer axial length (P < 0.001; odds ratio [OR], 7.13; 95% confidence interval [CI], 2.49-20.4), older age (P = 0.001; OR, 1.25; 95% CI, 1.10-1.42), higher prevalence of staphylomas (P = 0.03; OR, 24.3; 95% CI, 2.89-204), smaller parapapillary γ-zone in 2011 (P = 0.01; OR, 0.61; 95% CI, 0.41-0.91), and female gender (P = 0.04; OR, 9.78; 95% CI, 1.06-90.6). CONCLUSIONS: The 10-year progression rate of myopic maculopathy in this elderly Chinese population was 35.5%, increasing from 15 of 79 eyes (19%) in category 1 of myopic maculopathy at baseline to 17 of 24 eyes (71%) in category 2 and 6 of 6 eyes (100%) in category 3. Risk factors for myopic maculopathy progression were longer axial length, pre-existing staphylomata, smaller parapapillary γ-zone, older age, and female gender.

Evaluation of ecotourism suitability based on AHP-GIS: Taking Xiaoxiangling area of the Giant Panda National Park and the surrounding communities as an example.

The primary goal of national parks is to protect ecological environment, but also with the functions of scientific research, education, and recreation. Aiming for the realization of universal sharing, we used the analytic hierarchy process (AHP) to construct an ecotourism suitability evaluation system by selecting four factors, including landscape resources, ecological environment carrying capacity, recreation utilization capacity and social condition, taking Xiaoxiangling area of Giant Panda National Park and the surrounding communities as an example. We evaluated the ecotourism suitability based on GIS, and conducted a questionnaire survey of tourists, to propose suggestions on the functional zoning in terms of ecotourism suitability and subjective choice preferences of tourists. The results showed that the ecotourism suitability of the evaluation area could be classified into five levels. The most suitable areas were located nearby the natural landscape resources and far away from the core conservation area, and the least suitable areas distributed at the edge of the core conservation area. According to the results of suitability analysis, the evaluation area was divided into suitable development area, moderate development area, and restricted development area. Combined with the tourist preferences, we divided the recreational activities in the evaluation area into seven activities, namely, ecotourism, eco-camping, science education, leisure vacation, agricultural and animal husbandry culture experience, eco-education, and mountain adventure. These findings could help provide suitable services for different tourists and offer reference for the ecotourism developmental planning of the Xiaoxiangling area of the Giant Panda National Park.

High-sensitivity SrTiO3 photodetectors with paralleled multiple interdigital electrode cells.

We report high-sensitivity SrTiO(3) photoconductive detectors with multiple photoelectric cells connected in parallel. The photocurrent of the detectors increases significantly with an increase of the cell number. The photocurrent responsivity of the detector with three cells can reach 237 mA/W at 10 V bias under illumination of the 375 nm laser, and the corresponding quantum efficiency is 77% at 10 V bias. Furthermore, a transient photovoltaic signal with a rise time of ~490 ps and a full width at half-maximum of ~900 ps is obtained. These results demonstrate that the present devices with further improvement of performance have great potential application in high-sensitivity and ultrafast ultraviolet photodetectors.

Retinal nerve fiber layer thickness and retinal vascular caliber alterations in coal miners in northern China: a community-based observational study.

AIM: To evaluate retinal nerve fiber layer thickness and retinal vascular caliber alterations in coal mine workers. METHODS: The community-based observational cross-sectional study included 4004 participants of a sub-population of the Kailuan Study. All the study participants underwent structured interviews with a standardized questionnaire, fundus photography and spectral-domain optical coherence tomography (OCT) examinations performed by trained doctors. RESULTS: The retinal nerve fiber layer thickness was significantly higher (P=0.006) and the central macular thickness was lower in coal miners (n=659, 51.0±7.8y) as compared to the control (working above the ground; n=477, 51.8±7.5y; P=0.032). Additionally, the downhole workers showed a significantly thicker retinal artery (P=0.012) and vein diameters (P<0.001). In multivariable regression, a thicker retinal nerve fiber layer was associated with a higher cumulative silica dust exposure (P=0.005) after adjusting for younger age and larger spherical equivalent. In a reverse pattern, a higher cumulative silica dust exposure (P=0.004) was significantly associated with a thicker retinal nerve fiber layer after adjusting for age, high-density lipoproteins and uric acid. Wider retinal vein diameters were associated with higher cumulative silica dust exposure (P=0.036) after adjusting for younger age and larger spherical equivalent. CONCLUSION: The retinal vessels diameters and retinal nerve fiber layer thickness are significantly thicker in long term of coal mining. The results of our study indicate that underground working environment may lead to retinal vessel dilation and inflammation. Thus, ocular examination might be needed within coal miners in order to monitor the occupational eye health as well as the incidence and progression of eye diseases.

The Influence of Diabetes, Hypertension, and Hyperlipidemia on the Onset of Age-Related Macular Degeneration in North China: The Kailuan Eye Study.

Objective: To analyze the prevalence of dry and wet age-related macular degeneration (AMD) in patients with diabetes, hypertension and hyperlipidemia, and to analyze the risk factors for AMD. Methods: A population-based cross-sectional epidemiologic study was conducted involving 14,440 individuals. We assessed the prevalence of dry and wet AMD in diabetic and non-diabetic subjects and analyzed the risk factors for AMD. Results: The prevalence of wet AMD in diabetic and non-diabetic patients was 0.3% and 0.5%, respectively, and the prevalence of dry AMD was 17% and 16.4%, respectively. The prevalence of wet AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 0.5%, 0.3%, 0.2%, and 0.7%, respectively. The prevalence of dry AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 16.6%, 16.2%, 15.2%, and 17.2%, respectively. Age, sex, body mass index, and use of hypoglycemic drugs or lowering blood pressure drugs were corrected in the risk factor analysis of AMD. Diabetes, diabetes/hypertension, diabetes/hyperlipidemia, and diabetes/hypertension/hyperlipidemia were analyzed. None of the factors analyzed in the current study increased the risk for the onset of AMD. Conclusion: There was no significant difference in the prevalence of wet and dry AMD among diabetic and non-diabetic subjects. Similarly, there was no significant difference in the prevalence of wet and dry AMD among subjects with hypertension and hyperlipidemia. Diabetes co-existing with hypertension and hyperlipidemia were not shown to be risk factors for the onset of dry AMD.

Albuminuria and retinal vessel density in diabetes without diabetic retinopathy: the Kailuan Eye Study.

BACKGROUND: Diabetic retinopathy and chronic kidney disease are both major complications of diabetes mellitus. We explored the relationship between retinal vessel density (VD) and albuminuria in diabetic patients without conventionally defined diabetic retinopathy. METHODS: The cross-sectional community-based Kailuan Diabetic Retinopathy Study included patients with type 2 diabetes without diabetic retinopathy who participated in the community-based longitudinal Kailuan study and who had undergone ocular fundus photography, kidney function assessment, and optical coherence tomographic angiography (OCT-angiography) for the assessment the retinal perfusion density (PD) and retinal VD. RESULTS: The study included 447 patients (mean age: 60.9 ± 9.7 years). Higher PD and VD were associated with a lower urinary albumin-creatinine ratio (uACR) (macular region: p = 0.007: standardized regression coefficient beta: -0.14; and p = 0.008, beta: -0.13, respectively; parafoveal region: p = 0.006, beta: -0.14; and p = 0.007, beta: -0.14, respectively) after adjusting for age and ocular axial length. In a reverse manner, higher uACR was associated with lower PD and VD (macular region: p = 0.009, beta: -0.14; and p = 0.01, beta: -0.14, respectively; parafoveal region: p = 0.008, beta: -0.14; and p = 0.01, beta: -0.14, respectively), after adjusting for diabetes duration, blood pressure, serum concentration of C-reactive protein and high-density lipoprotein cholesterol and ocular axial length. In a multivariable model, the prevalence of macroalbuminuria increased by 11% (95% CI: 2%, 18%) and 17% (95% CI: 3%, 30%), respectively, for each mm-1 decrease in VD and each unit decrease in PD. CONCLUSIONS AND RELEVANCE: After adjusting for systemic and ocular parameters, diabetic patients without diabetic retinopathy showed a reduction in OCT-angiographic retinal vascular measurements in association with systemic parameters indicating chronic kidney disease. Optical coherence tomographic (OCT)-angiographic retinal microvascular parameters may serve as markers for chronic kidney disease.

Application of network pharmacology and molecular docking to elucidate the potential mechanism of Eucommia ulmoides-Radix Achyranthis Bidentatae against osteoarthritis.

BACKGROUND: Osteoarthritis is a disabling disease, which seriously affects the quality of life of patients. Increasing evidence has indicated that Chinese herbal medicine including Eucommia ulmoides (EU) and Radix Achyranthis Bidentatae (RAB) have potential in the treatment of osteoarthritis, and this is associated with their multi-target and multi-link action characteristics. Although their potential anti-arthritic activity has been reported, the exact mechanism of EU-RAB action in osteoarthritis remains unexplored. Therefore, this study explores the mechanism of EU-RAB against osteoarthritis using network pharmacology and molecular docking technology. METHODS: Public databases including TCMSP、BATMAN-TCM、OMIM and Genecards were used to predict the bioactive ingredients and putative targets of EU-RAB against osteoarthritis. Enrichment analysis was performed to expound the biological functions and associated pathways of the hub targets. Cytoscape software was used to construct a "compounds-targets-pathways" network for elucidating the comprehensive molecular mechanism of EU-RAB against osteoarthritis. Molecular docking was used to verify the correlation between the main active ingredients and hub targets. RESULTS: Network pharmacological analysis of EU-RAB in the treatment of osteoarthritis, identified 50 active ingredients including quercetin, kaempferol, wogonin, and baicalein with important biological effect. A total of 68 key targets were screened, including IL-6, EGFR, MAPK8, etc., and they were found to be enriched in a series of signaling pathways, such as apoptosis, TNF, MAPK, PI3K/AKT, and IL-17 signaling pathways. Moreover, molecular docking analysis showed that the main ingredients were tightly bound to the core targets, further confirming the anti-arthritic effects. CONCLUSION: Based on network pharmacology and molecular docking analysis, the present study provides insights into the potential mechanism of EU-RAB in osteoarthritis after successfully screening for associated key target genes and signaling pathways. These findings further provide a theoretical basis for further pharmacological research into the potential mechanism of EU-RAB in osteoarthritis.

MicroRNA-145 suppresses uveal melanoma angiogenesis and growth by targeting neuroblastoma RAS viral oncogene homolog and vascular endothelial growth factor.

BACKGROUND: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. It has been demonstrated that microRNA-145 (miR-145) is correlated with the progression of various cancers by regulating the expression of multiple target genes, especially a number of genes that regulate angiogenesis and proliferation. However, the underlying mechanisms of miR-145 in tumor angiogenesis of UM are still not well illustrated. Thus, we aimed to explore the potential target genes or pathways regulated by miR-145 in UM and the effect of miR-145 on invasion and angiogenesis. METHODS: Totally, 24 choroid samples were collected in our study, including 12 UM samples and 12 normal uveal tissues. The expression of neuroblastoma RAS viral oncogene homolog (N-RAS), phosphorylated protein kinase B (p-AKT), and vascular endothelial growth factor (VEGF) in UM tissues and normal uveal tissues was analyzed using Western blotting analysis. Lentivirus expression system was used to construct MUM-2B and OCM-1 cell lines with stable overexpression of miR-145. Transwell and endothelial cell tube formation assay were used to measure the effects of miR-145 on the invasion and angiogenesis of UM in vitro. The downstream target genes of miR-145 were predicted by bioinformatics and confirmed using a luciferase assay. BALB/c nude mice models were established to investigate the mechanisms of miR-145 on tumor growth and angiogenesis in vivo. Group data comparisons were performed using analysis of Student's t test. A two-tailed P < 0.05 was considered as statistically significant. RESULTS: The results of Western blotting analysis indicated that the expressions of N-RAS (1.10 ±â€Š0.35 vs. 0.41 ±â€Š0.36, t = 3.997, P = 0.012), p-AKT (1.16 ±â€Š0.22 vs. 0.57 ±â€Š0.03, t = 7.05, P = 0.001), and VEGF (0.97 ±â€Š0.32 vs. 0.45 ±â€Š0.21, t = 3.314, P = 0.008) in UM tumor tissues were significantly higher than those in normal uveal tissue. Luciferase assay demonstrated N-RAS and VEGF as downstream targets of miR-145. Moreover, tube formation assay revealed that miR-145-transfected human microvascular endothelial cell line formed shorter tube length (36.10 ±â€Š1.51 mm vs. 42.91 ±â€Š0.94 mm, t = 6.603, P = 0.003) and less branch points (350.00 ±â€Š19.97 vs. 406.67 ±â€Š17.62, t = 3.685, P = 0.021) as compared with controls. In addition, the numbers of invaded MUM-2B and OCM-1 cells with miR-145 overexpression were significantly lower than the controls (35.7 ±â€Š3.3 vs. 279.1 ±â€Š4.9, t = 273.75, P < 0.001 and 69.5 ±â€Š4.4 vs. 95.6 ±â€Š4.7, t = 21.27, P < 0.001, respectively). In vivo, xenografts expressing miR-145 had smaller sizes (miR-145 vs. miR-scr, 717.41 ±â€Š502.62 mmvs. 1694.80 ±â€Š904.33 mm, t = 2.314, P = 0.045) and lower weights (miR-145 vs. miR-scr, 0.74 ±â€Š0.46 g vs. 1.65 ±â€Š0.85 g, t = 2.295, P = 0.045). CONCLUSION: Our results indicated that miR-145 is an important tumor suppressor and the inhibitory strategies against N-RAS/VEGF signaling pathway might be potential therapeutic applications for UM in the future.

Ocular Axial Length and Diabetic Retinopathy: The Kailuan Eye Study.

Purpose: To examine the role of ocular axial length as an ocular parameter for the prevalence and severity of diabetic retinopathy (DR). Methods: The cross-sectional Kailuan Diabetic Retinopathy Study included patients with diabetes who participated in the community-based longitudinal Kailuan Study and who had undergone ocular fundus photography. The fundus photographs were graded using the Early Treatment of Diabetic Retinopathy Study criteria. Results: The study included 1096 patients with diabetes (mean age: 60.8 ± 9.4 years; axial length: 23.37 ± 0.92 mm). In binary regression analysis, a higher DR prevalence was associated with shorter axial length (P = 0.007; odds ratio [OR]: 0.81; 95% confidence interval [CI]: 0.70, 0.95) after adjusting for longer known duration of diabetes (P = 0.02; OR: 1.13; 95%CI: 1.02, 1.24) and higher fasting blood glucose concentration (P < 0.001; OR: 1.38; 95%CI: 1.26, 1.52). A more severe DR stage was associated (regression coefficient r: 0.46) with shorter ocular axial length (P = 0.047; standardized regression coefficient ß: -0.06) after adjusting for higher fasting blood glucose (P < 0.001; ß: 0.41) and longer known duration of diabetes (P = 0.045; ß: 0.07). Longer axial length was associated with a lower DR prevalence (P = 0.003; ß: -0.10) after adjusting for younger age (P < 0.001), male sex (P < 0.001), higher body mass index (P = 0.016), and lower fasting blood glucose concentration (P = 0.036). Conclusions: After adjusting for systemic risk factors, DR prevalence decreased by 19% (95%CI: 5, 30) for each millimeter increase in axial length. With longer axial length being a surrogate for axial myopia, the marked increase in myopia prevalence worldwide may lead to a relative decrease in the prevalence and incidence of DR in future.

10-year fundus tessellation progression and retinal vein occlusion.

AIM: To access the 10-year fundus tessellation progression in patients with retinal vein occlusion. METHODS: The Beijing Eye Study 2001/2011 is a population-based longitudinal study. The study participants underwent a detailed physical and ophthalmic examination. Degree of fundus tessellation was graded by using fundus photographs of the macula and optic disc. Progression of fundus tessellation was calculated by fundus tessellation degree of 2011 minus degree of 2001. Fundus photographs were used for assessment of retinal vein occlusion. RESULTS: The Beijing Eye Study included 4403 subjects in 2001, 3468 subjects was repeated in 2011. Assessment of retinal vein obstruction and fundus tessellation progression were available for 2462 subjects (71.0%), with 66 subjects fulfilled the diagnosis of retinal vein occlusion. Of the 66 participants, 59 participants with unilateral branch retinal vein occlusion, 5 participants with unilateral central retinal vein occlusion, 1 participant with bilateral branch retinal vein occlusion, and 1 participant with branch retinal vein occlusion in one eye and central retinal vein occlusion in the other eye. Mean degree of peripapillary fundus tessellation progression were significantly higher in the whole retinal vein occlusion group (0.33±0.39, P<0.001), central retinal vein occlusion group (0.71±0.8, P=0.025) and branch retinal vein occlusion group (0.29±0.34, P=0.006) than the control group (0.20±0.26). After adjustment for age, prevalence of tilted disc, change of best corrected visual acuity, axial length, progression of peripapillary fundus tessellation was associated with the presence of retinal vein occlusion (P=0.004; regression coefficient B, 0.094; 95%CI, 0.029, 0.158; standardized coefficient B, 0.056). As a corollary, after adjusting for smoking duration, systolic blood pressure, anterior corneal curvature, prevalence of RVO was associated with more peripapillary fundus tessellation progression (P<0.001; regression coefficient B: 1.257; OR: 3.517; 95%CI: 1.777, 6.958). CONCLUSION: Peripapillary fundus tessellation progresses faster in individuals with retinal vein occlusion. This may reflect the thinning and hypoperfusion of choroid in patients with retinal vein occlusion.

Long-term Progression and Risk Factors of Fundus Tessellation in the Beijing Eye Study.

To assess the progression of fundus tessellation, color fundus photographs of the participants of the longitudinal population-based Beijing Eye Study were examined. The study included 4439 subjects in 2001 and 2695 (66.4% of the surviving) individuals in 2011. Larger progression in macular fundus tessellation (mean: 0.24 ± 0.48 grades) was associated (multivariate analysis; correlation coefficient r: 0.53) with thinner subfoveal choroidal thickness in 2011 (P < 0.001; standardized regression coefficient beta: -0.37), older age (P < 0.001; beta: 0.22), higher level of education (P < 0.001; beta: 0.09), more myopic change in refractive error (P < 0.001; beta: -0.09) and lower cognitive function score (P = 0.02; beta: -0.05). Larger increase in peripapillary fundus tessellation (mean: 0.19 ± 0.26 grades) correlated with thinner peripapillary choroidal thickness in 2011 (P < 0.001; beta: -0.35), older age (P < 0.001; beta: 0.20), worse best corrected visual acuity (P = 0.001; beta: 0.07), more myopic change in refractive error (P < 0.001; beta: -0.07) and higher prevalence of ever smoking (P = 0.004; beta: 0.05). The increase in macular fundus tessellation, as a surrogate for thinning of the posterior choroid, was associated with lower cognitive function, after adjusting for choroidal thickness, age, educational level and change in refractive error. The findings point to the clinical value of the assessment of fundus tessellation and suggest potential associations between cognitive function and fundus tessellation/choroidal thickness.

Synthesis and electrochemical properties of chemically substituted LiMn2O4 prepared by a solution-based gel method.

Lithium manganese oxide, LiMn(2)O(4), and its substituted samples LiM(0.05)Mn(1.95)O(4) (M=Al, Co, and Zn) were first prepared by a cost-saving and effective new solution-based gel method using a mixture of acetate and ethanol as the chelating agent. The physical properties of the synthesized samples were investigated by thermogravimetry/differential thermal analysis, X-ray diffraction, and scanning electronic microscopy. The as-prepared powders were used as positive materials for a lithium-ion battery, whose charge/discharge properties and cycle performance were examined. The results revealed that all the substituted samples had better cycle performance than pure LiMn(2)O(4). Among these synthesized materials, the LiCo(0.05)Mn(1.95)O(4) sample had the best cycle performance. After 30 cycles, its capacity loss was only 3%. Therefore, cyclic voltammetry and electrochemical impedance spectroscopy were employed to characterize the reactions of Li ion insertion into and extraction from LiCo(0.05)Mn(1.95)O(4) electrodes.

Enhancement of the electrochemical properties of LiMn2O4 through Al3+ and F- co-substitution.

The cathode-active materials LiMn2O4, LiAl0.1Mn1.9O4, and LiAl0.1Mn1.9O3.9F0.1 were synthesized by a microwave-assisted sol-gel method. The influence of different doping elements on the structural and electrochemical properties of the as-prepared samples was investigated by thermogravimetric analysis (TGA), X-ray diffraction (XRD), transmission electron microscopy (TEM), and electrochemical experiments. The results indicated that fluorine plays an important role in controlling the morphology, and the doped aluminum could enhance significantly the stability of spinel-type LiMn2O4. The initial discharge capacity of the Al3+ and F- co-substituted specimen reached 129.8 mA h/g and has a high capacity retention after 40 cycles. The outstanding electrochemical properties of LiAl0.1Mn1.9O3.9F0.1 make it a possible promising cathode material for lithium-ion batteries.

Pharmacokinetics, safety and tolerability of L-3-n-butylphthalide tablet after single and multiple oral administrations in healthy Chinese volunteers

L-3-n-butylphthalide (L-NBP) is a naturally occurring antioxidant, which can be used for the treatment of acute ischemic stroke and vascular dementia. This study evaluated the safety, tolerability and pharmacokinetics of L-NBP tablets in healthy Chinese volunteers. This was a single-center, randomized, double-blind, placebo-controlled, single- and multiple-dose study. Subjects were assigned to receive a single dose of L-NBP tablet at either 80, 160, 320, or 480 mg (n=40), or multiple doses of 160 mg twice daily for 7 days (n=12). Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters of L-NBP were calculated using non-compartmental analysis with WinNonlin software. Statistical analysis was performed using SPSS software. All adverse events (AEs) were mild and of limited duration; AEs in this study occurred less frequently and more mildly than AEs listed for the DL-NBP soft capsule. No serious adverse event (SAE), death or withdrawal from the study was observed. In the single-dose study, Cmax was reached at about 1 h, and the mean t1/2 was approximately 13.76 h. Area under curve (AUC) and Cmax increased with dose escalation, but dose proportionality was not observed over the range of 160 to 480 mg. In the multiple-dose study, the steady-state was reached within 3 days with slight accumulation. In summary, the L-NBP tablet was well tolerated in healthy Chinese subjects. Slight accumulation appeared after repeated doses.

L-3-n-butilftalida (L-NMP) é um antioxidante natural, que pode ser utilizado para o tratamento do acidente isquêmico agudo e demência vascular. Este estudo avaliou segurança, tolerância e farmacocinética de comprimidos de L-NBP em chineses voluntários sadios. Este foi um estudo monocêntrico, randomizado, duplo cego, com controle por placebo e doses única e múltipla. Os indivíduos receberam dose única de comprimido de L-NBP de 80, 160, 320 ou 480 mg (n=40) e doses múltiplas de 160 mg duas vezes ao dia, por sete dias (n=12). Amostras de plasma foram analisadas com LC-MS/MS. Os parâmetros farmacocinéticos do L-NBP foram calculados utilizando análise não compartimental, com o programa WinNonlin. A análise estatística foi realizada utilizando-se o programa SPSS. Todos os eventos adversos (EAs) foram moderados e de duração limitada. EAs nesse estudo ocorreram menos frequentemente e mais moderadamente do que os EAs relacionados para cápsulas moles de DL-NBP. Não se observaram eventos adversos graves (EAG), morte ou abandono do estudo. Com dose única, atingiu-se o Cmax em cerca de 1 hora e o t1/2 médio foi de, aproximadamente, 13,76 h. A área sob a curva (ASC) e o Cmax aumentaram com o aumento da dose, mas não se observou proporcionalidade na faixa acima de 160 a 480 mg. No estudo de dose múltipla, o equilíbrio foi alcançado em três dias, com pequeno acúmulo. Em resumo, o comprimido de L-NMP foi bem tolerado em indivíduos chineses saudáveis. O acúmulo pequeno apareceu após doses repetidas.