Therapeutic effect and mechanism of Yougui Wan in rats with intervertebral disk degeneration.

OBJECTIVE: To explore the potential mechanism of Yougui Wan on deformed lumbar intervertebral disk structure in rats. METHODS: Thirty male Sprague-Dawley rats were randomly divided into 3 groups, with 10 rats in each group. The animals in the blank control group were healthy rats without specific treatment, and those in the model group and traditional Chinese medicine (TCM) group were used to establish the intervertebral disk degeneration (IDD) model by puncturing the annulus. Four weeks after modeling, rats in the TCM group were administered Yougui Wan by gavage for 2 consecutive weeks. Serum interleukin-6 (IL-10), macrophage migration inhibitory factor (MIF) and tumor necrosis factor alpha (TNF-α) levels were measured by ELISA, and the protein expression levels of collagen II and Notch1 in intervertebral disk tissues were examined by Western blotting. Apoptosis was detected by the TUNEL method. RESULTS: Compared with those in the blank group, IL-10, MIF and TNF-α levels in the model group and TCM group were increased (P < 0.05), the protein expression levels of collagen II were decreased, and the protein expression levels of Notch1 were increased. Compared with those in the model group, the levels of IL-10 in the TCM group were increased (P < 0.05), the levels of MIF and TNF-α were decreased (P < 0.05), the protein expression levels of collagen II were increased, and the protein expression levels of Notch1 were decreased. CONCLUSION: Yougui Wan can inhibit the inflammatory response in IDD rats, reduce the degradation of extracellular matrix, reduce apoptosis in nucleus pulposus cells, and alleviate intervertebral disk degeneration. The mechanism may be related to the regulation of the Notch signaling pathway.

Comparative Study of Ultrasonography and Ultra-Widefield Fundus Photographs for Measurements of the Diameter of Choroidal and Retinal Tumors.

INTRODUCTION: Measurement of the largest basal dimension (LBD) of intraocular tumors is important as a prognostic parameter. To evaluate the potential value of true color ultra-widefield fundus photography for measuring tumors, we compared LBD measurements of choroidal and retinal tumors using a color ultra-widefield fundus camera with clinical estimation based on indirect ophthalmoscopy and standardized ophthalmic ultrasound. METHODS: The LBD of 148 choroidal and retinal tumors in 148 patients seen at Tongren Hospital were measured using ultra-widefield fundus photography and compared with measurements obtained using B-scan ultrasonography and clinical estimates based on indirect ophthalmoscopy. RESULTS: Paired t-tests and Bland-Altman plots reveal that measurements from ultra-widefield fundus photographic images are not statistically different from clinical estimates and ultrasound measurements. The results also showed that, although not statistically significant, when the tumor boundary was clear, the height was < 3 mm, or the tumor was pigmented, measurement from ultra-widefield fundus photography tended to be greater than those obtained by ultrasound. CONCLUSIONS: The LBD measurement using ultra-widefield fundus photography correlated well with ultrasonography and clinical estimation and could be used as a reliable tool for measuring the LBD of choroidal and retinal tumors.

Toward Antifragility: Social Defeat Stress Enhances Learning and Memory in Young Mice Via Hippocampal Synaptosome Associated Protein 25.

Social adversity not only causes severe psychological diseases but also may improve people's ability to learn and grow. However, the beneficial effects of social adversity are often ignored. In this study, we investigated whether and how social adversity affects learning and memory in a mouse social defeat stress (SDS) model. A total of 652 mice were placed in experimental groups of six to 23 mice each. SDS enhanced spatial, novelty, and fear memory with increased synaptosome associated protein 25 (SNAP-25) level and dendritic spine density in hippocampal neurons among young but not middle-aged mice. Chemogenetic inhibition of hippocampal CaMK2A+ neurons blocked SDS-induced enhancement of learning or memory. Knockdown of SNAP-25 or blockade of N-methyl-D-aspartate (NMDA) receptor subunit GluN2B in the hippocampus prevented SDS-induced learning memory enhancement in an emotion-independent manner. These findings suggest that social adversity promotes learning and memory ability in youths and provide a neurobiological foundation for biopsychological antifragility.

Analysis of risk and protective factors associated with retinal nerve fiber layer defect in a Chinese adult population.

AIM: To investigate the risk and protective factors associated with the retinal nerve fiber layer defect (RNFLD) in a Chinese adult population. METHODS: This study was a cross-sectional population-based investigation including employees and retirees of a coal mining company in Kailuan City, Hebei Province. All the study participants underwent a comprehensive systemic and ophthalmic examination. RNFLD was diagnosed on fundus photographs. Binary logistic regression was used to investigate the risk and protective factors associated with the RNFLD. RESULTS: The community-based study included 14 440 participants. There were 10 473 participants in our study, including 7120 males (68.0%) and 3353 females (32.0%). The age range was 45-108y, averaging 59.56±8.66y. Totally 568 participants had RNFLD and the prevalence rate was 5.42%. A higher prevalence of RNFLD was associated with older age [P<0.001, odds ratio (OR): 1.032; 95% confidence interval (CI): 1.018-1.046], longer axial length (P=0.010, OR: 1.190; 95%CI: 1.042-1.359), hypertension (P=0.007, OR: 0.639; 95%CI: 0.460-0.887), and diabetes mellitus (P=0.019, OR: 0.684; 95%CI: 0.499-0.939). The protective factors of RNFLD were visual acuity (P=0.038, OR: 0.617; 95%CI: 0.391-0.975), and central anterior chamber depth (P=0.046, OR: 0.595; 95%CI: 0.358-0.990). CONCLUSION: In our cross-sectional community-based study, with an age range of 45-108y, RNFLD is associated with older age, longer axial length, hypertension, and diabetes mellitus. The protective factors of RNFLD are visual acuity and central anterior chamber depth. These can help to predict and evaluate RNFLD related diseases and identify high-risk populations early.

Size selection and placement of pedicle screws using robot-assisted versus fluoroscopy-guided techniques for thoracolumbar fractures: possible implications for the screw loosening rate.

BACKGROUND: There has been increased development of robotic technologies for the accuracy of percutaneous pedicle screw placement. However, it remains unclear whether the robot really optimize the selection of screw sizes and enhance screw stability. The purpose of this study is to compare the sizes (diameter and length), placement accuracy and the loosening rate of pedicle screws using robotic-assisted versus conventional fluoroscopy approaches for thoracolumbar fractures. METHODS: A retrospective cohort study was conducted to evaluate 70 consecutive patients [34 cases of robot-assisted percutaneous pedicle screw fixation (RAF) and 36 of conventional fluoroscopy-guided percutaneous pedicle screw fixation (FGF)]. Demographics, clinical characteristics, and radiological features were recorded. Pedicle screw length, diameter, and pedicle screw placement accuracy were assessed. The patients' sagittal kyphosis Cobb angles (KCA), anterior vertebral height ratios (VHA), and screw loosening rate were evaluated by radiographic data 1 year after surgery. RESULTS: There was no significant difference in the mean computed tomography (CT) Hounsfield unit (HU) values, operation duration, or length of hospital stay between the groups. Compared with the FGF group, the RAF group had a lower fluoroscopy frequency [14 (12-18) vs. 21 (16-25), P < 0.001] and a higher "grade A + B" pedicle screw placement rate (96.5% vs. 89.4%, P < 0.05). The mean screw diameter was 6.04 ± 0.55 mm in the RAF group and 5.78 ± 0.50 mm in the FGF group (P < 0.001). The mean screw length was 50.45 ± 4.37 mm in the RAF group and 48.63 ± 3.86 mm in the FGF group (P < 0.001). The correction loss of the KCA and VHR of the RAF group was less than that of the FGT group at the 1-year follow-up [(3.8 ± 1.8° vs. 4.9 ± 4.2°) and (5.5 ± 4.9% vs. 6.4 ± 5.7%)], and screw loosening occurred in 2 out of 34 patients (5.9%) in the RAF group, and 6 out of 36 patients (16.7%) in the FGF group, but there were no significant differences (P > 0.05). CONCLUSION: Compared with the fluoroscopy-guided technique, robotic-assisted spine surgery decreased radiation exposure and optimizes screw trajectories and dimensions intraoperatively. Although not statistically significant, the loosening rate of the RAF group was lower that of than the FGT group.

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.

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.

[Comparison of endogenetic microbial community diversity between wild Cordyceps sinensis,artificial C. sinensis and habitat soil].

To obtain the difference of the fungal and bacterial community diversity between wild Cordyceps sinensis, artificial C. sinensis and their habitat soil, Illmina Hiseq high-throughput sequencing technology was applied. The results show that Proteobacteria was the dominant bacterial phylum in C. sinensis, Actinobacteria was the dominant bacterial phylum in soil microhabitat, Ophiocordyceps sinensis was the predominant dominant fungus of C. sinensis. The α diversity analysis showed that the fungal diversity of stroma was lower than other parts, and the fungal diversity of wild C. sinensis was lower than that of artificial C. sinensis. The ß diversity analysis showed that the fungal and bacterial community diversity of soil microhabitat samples was significantly different from that of C. sinensis. The fungal community diversity was less different between wild and artificial C. sinensis, especially in sclerotia. LEfSe analysis showed a lot of species diversity between wild and artificial C. sinensis. Those different species between wild C. sinensis, artificial C. sinensis and their habitat soil provide ideas for further research on breed and components of C. sinensis.

Retinal Protection by Sustained Nanoparticle Delivery of Oncostatin M and Ciliary Neurotrophic Factor Into Rodent Models of Retinal Degeneration.

Purpose: Retinitis pigmentosa (RP) is caused by mutations in more than 60 genes. Mutation-independent approaches to its treatment by exogeneous administration of neurotrophic factors that will preserve existing retinal anatomy and visual function are a rational strategy. Ciliary neurotrophic factor (CNTF) and oncostatin M (OSM) are two potent survival factors for neurons. However, growth factors degrade rapidly if administered directly. A sustained delivery of growth factors is required for translating their potential therapeutic benefit into patients. Methods: Stable and biocompatible nanoparticles (NP) that incorporated with CNTF and OSM (CNTF- and OSM-NP) were formulated. Both NP-trophic factors were tested in vitro using photoreceptor progenitor cells (PPC) and retinal ganglion progenitor cells (RGPC) derived from induced pluripotent stem cells and in vivo using an optic nerve crush model for glaucoma and the Royal College of Surgeons rat, model of RP (n = 8/treatment) by intravitreal delivery. Efficacy was evaluated by electroretinography and optokinetic response. Retinal histology and a whole mount analysis were performed at the end of experiments. Results: Significant prosurvival and pro-proliferation effects of both complexes were observed in both photoreceptor progenitor cells and RGPC in vitro. Importantly, significant RGC survival and preservation of vision and photoreceptors in both complex-treated animals were observed compared with control groups. Conclusions: These results demonstrate that NP-trophic factors are neuroprotective both in vitro and in vivo. A single intravitreal delivery of both NP-trophic factors offered neuroprotection in animal models of retinal degeneration. Translational Relevance: Sustained nanoparticle delivery of neurotrophic factors may offer beneficial effects in slowing down progressive retinal degenerative conditions, including retinitis pigmentosa, age-related macular degeneration, and glaucoma.

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.

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.

Prevalence and Risk Factors of Epiretinal Membranes in a Chinese Population: The Kailuan Eye Study.

Purpose: To investigate the prevalence of epiretinal membranes (ERMs) and their risk factors in a Chinese population. Methods: The community-based Kailuan Eye Study included 14,440 participants (9835 male, 4605 female) with a mean age of 54.0 ± 13.3 years (range, 20-110 years). They underwent a systemic and ophthalmologic examination. ERMs were diagnosed on fundus photographs. Results: Retinal photographs assessable for the presence of ERMs were available for 13,295 (92.0%) individuals (9094 male) with a mean age of 53.6 ± 13.3 years (range, 20-110 years). ERMs were found in 1013 participants (1489 eyes) with a prevalence of 7.6% (95% confidence interval [CI], 7.1%-8.1%). Secondary ERMs caused by intraocular reasons were found 46 (4.5%) individuals (69 [4.6%] eyes). A higher prevalence of any ERMs (and of primary ERMs) was associated with older age (odds ratio [OR]: 1.08; 95% CI:1.07-1.10), higher body mass index (OR: 1.05; 95% CI: 1.00-1.11), higher prevalence of smoking (OR:1.43; 95% CI: 1.01-2.03), higher serum concentration of glucose (OR: 1.08; 95% CI: 1.04-1.13), and lower serum concentration of uric acid (OR: 0.99; 95% CI: 0.99-1.00). Visual acuity was significantly (P = 0.002) lower in eyes with premacular fibroses than in eyes with cellophane macular reflexes. Conclusions: In our cross-sectional community-based study, the prevalence of all ERMs was 7.6%. Among the group of participants with ERMs, secondary ERMs caused by intraocular reasons were detected in 46 (4.5%) individuals (69 [4.6%] eyes). A higher prevalence of any ERM and of primary ERMs was associated with older age, higher body mass index, higher prevalence of smoking, a higher serum concentration of glucose, and a lower serum concentration of uric acid.

Influencing factors for peripheral and posterior lesions in mild non-proliferative diabetic retinopathy-the Kailuan Eye Study.

AIM: To explore the influencing factors of diabetes type 2 patients with mild non-proliferative diabetic retinopathy (NPDR) in the Kailuan area of Tangshan, Hebei Province, China. METHODS: In this non-interventional, retrospective study, 683 patients with type 2 diabetes were included in the Kailuan Diabetic Retinopathy Study involving participants with diabetes in the community-based longitudinal Kailuan Study. Based on the undilated ultra-wide field (200°; UWF) images and partial dilated digital fundus images, the diabetic retinopathy (DR) of the surveyed population was graded. Interobserver agreement was estimated by using Cohen's Kappa statistics. The main outcome indicators included gender, age, weight, height, body mass index, blood pressure, circumferences of neck, waist and hip, current smoking, levels of fasting plasma glucose (FPG), hypersensitive C-reactive protein, creatinine, and cholesterol, etc. According to different lesions' locations of patients with mild NPDR, logistic regression models were used to estimate the odds ratios (ORs) and their 95%CIs of each risk factor. RESULTS: The study group of 683 patients included 570 males and 113 females. The mean age of the patients was 62.18±9.41y. Compared with dilated fundus examinations, there was fair agreement with the level of DR identified on UWF images in 63.91% of eyes (k=0.369, 95%CI, 0.00-0.00). Detected by UWF images, there were 98 patients with mild NPDR having peripheral retinal lesions, 35 patients with mild NPDR having posterior lesions, 44 patients with mild NPDR whose lesions were detected both in and out the standard two fields area, and 336 patients with non obvious DR. Parameters that conferred a statistically significant increased risks for mild NPDR with having peripheral retinal lesions were neck circumstance (OR, 1.124; 95%CI, 1.044-1.211), and with posterior lesions were FPG (OR, 1.052; 95%CI, 1.007-1.099). CONCLUSION: UWF is an effectiveness means of DR screening. Moreover, it is necessary to evaluate peripheral diabetic retinal lesions which can help to estimate the severity of DR. The phenomenon that nonuniform and inhomogeneous distribution of DR lesions has been found. And the influencing factors in mild NPDR are differing by different lesions' locations.

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.

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.

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.

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.

The Anti-Inflammatory Effects of Vitamin D in Tumorigenesis.

In conjunction with the classical functions of regulating intestinal, bone, and kidney calcium and phosphorus absorption, as well as bone mineralization of vitamin D, the population-based association between low vitamin D status and increased cancer risk is now generally accepted. Inflammation is causally related to oncogenesis. It is widely thought that vitamin D plays an important role in the modulation of the inflammation system by regulating the production of inflammatory cytokines and immune cells, which are crucial for the pathogenesis of many immune-related diseases. Mechanistic studies have shown that vitamin D influences inflammatory processes involved in cancer progression, including cytokines, prostaglandins, MAP kinase phosphatase 5 (MKP5), the nuclear factor kappa B (NF-κB) pathway, and immune cells. Multiple studies have shown that vitamin D has the potential to inhibit tumor development by interfering with the inflammation system. The present review summarizes recent studies of the mechanisms of vitamin D on regulating the inflammation system, which contributes to its potential for cancer prevention and therapy. This review helps answer whether inflammation mediates a causal relationship between vitamin D and tumorigenesis.

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.