Association between visceral fat area and diabetic retinopathy among people with type 2 diabetes mellitus: a cross-sectional study in Ningbo, Zhejiang Province, China.

Aim: The objective of this study is to investigate the relationship between visceral fat area (VFA) and diabetic retinopathy (DR) in the context of type 2 diabetes mellitus (T2DM) within Ningbo, China. Methods: The data of a total of 3,707 subjects with T2DM treated at The First Affiliated Hospital of Ningbo University were enrolled. The existence and severity of diabetic retinopathy were assessed by employing the 45° two-field stereoscopic digital photography. Subjects were categorized into four distinct groups: those without DR (NDR), individuals with mild non-proliferative DR (mild NPDR), people with moderate non-proliferative DR (moderate NPDR), and those suffering from vision-threatening DR (VTDR). Bio-electrical impedance was employed to estimate the Visceral fat area (VFA). Multinomial logistic regression models were utilized to evaluate the association between VFA and DR. Results: The mean VFA in patients without diabetic retinopathy (NDR) was notably lower compared to that of patients with diabetic retinopathy (DR) (85.21 ± 37.78 vs. 97.37 ± 44.58 cm2, p < 0.001). As the severity of DR increased, VFA increased gradually but insignificantly (94.41 ± 43.13 cm2, 96.75 ± 40.82 cm2, 100.84 ± 49.34 cm2, p = 0.294). After adjusting the confounding factors, there was an association identified between VFA and the occurrence of DR (OR = 1.020, 95% CI = 1.016-1.024). It showed that regardless of BMI, whether it's less than 25 kg/m2 or greater than or equal to 25 kg/m2, a higher VFA (≥100 cm2) level came with a higher prevalence of DR (p < 0.001). Conclusion: The outcomes of this research indicate a modest association between VFA and the incidence of DR among Chinese patients who have been diagnosed with T2DM in Ningbo.

Association of vitamin B6 intake with the risk and prognosis of diabetic retinopathy: a NHANES-based study.

CLINICAL RELEVANCE: Investigating the role of dietary vitamin B6 intake in the risk and prognosis of diabetic retinopathy (DR) could facilitate the management of DR. BACKGROUND: This study aimed to assess the association between dietary vitamin B6 intake and the risk of DR and further explore the association between vitamin B6 intake and mortality in patients with DR. METHODS: This retrospective cohort study gained data from the National Health and Nutrition Examination Survey (NHANES) 2005-2006 and 2007-2008. The intake of dietary vitamin B6 was assessed by two 24-h dietary recall interviews. Mortality information in the National Death Index was recorded from the date of survey participation through 31 December 2019. Multivariate regression analyses were employed to assess the association between vitamin B6 intake and the risk of DR, and the association between vitamin B6 intake and the risk of mortality in patients with DR. RESULTS: A total of 5559 subjects were included, of which 693 (12.47%) had DR. Among these patients with DR, 429 (61.90%) were survivors. Multivariate analyses showed that the intake of vitamin B6 was negatively associated with the risk of DR (odds ratio = 0.81, 95% confidence level: 0.69-0.95, p = 0.012), and patients with DR with an increased intake of vitamin B6 had a significantly decreased risk of all-cause death (hazard ratio = 0.81, 95% confidence level: 0.66-0.99, p = 0.041) or cardiovascular disease-related death (hazard ratio = 0.76, 95% confidence level: 0.58-0.98, p = 0.037). CONCLUSION: The intake of vitamin B6 was negatively associated with the risk of DR, and in patients with DR, a higher intake of vitamin B6 was associated with a lower risk of all-cause death and cardiovascular disease-related death, indicating the possible protective role of increased vitamin B6 intake.

Microvesicles facilitate the differentiation of mesenchymal stem cells into pancreatic beta-like cells via miR-181a-5p/150-5p.

Transplantation of pancreatic islet cells is a promising strategy for the long-term treatment of type 1 diabetes (T1D). The stem cell-derived beta cells showed great potential as substitute sources of transplanted pancreatic islet cells. However, the current efficiency of stem cell differentiation still cannot match the requirements for clinical transplantation. Here, we report that microvesicles (MVs) from insulin-producing INS-1 cells could induce mesenchymal stem cell (MSC) differentiation into pancreatic beta-like cells. The combination of MVs with small molecules, nicotinamide and insulin-transferrin-selenium (ITS), dramatically improved the efficiency of MSC differentiation. Notably, the function of MVs in MSC differentiation requires their entry into MSCs through giant pinocytosis. The MVs-treated or MVs combined with small molecules-treated MSCs show pancreatic beta-like cell morphology and response to glucose stimulation in insulin secretion. Using high throughput small RNA-sequencing, we found that MVs induced MSC differentiation into the beta-like cells through miR-181a-5p/150-5p. Together, our findings reveal the role of MVs or the MV-enriched miR-181a-5p/150-5p as a class of biocompatible reagents to differentiate MSCs into functional beta-like cells and demonstrate that the combined usage of MVs or miR-181a-5p/150-5p with small molecules can potentially be used in making pancreatic islet cells for future clinical purposes.

Quantitative analysis of early diabetic retinopathy based on optical coherence tomography angiography biological image.

BACKGROUND: With the development of the economy and improvements in living standards, the incidences of diabetes mellitus (DM) and diabetic retinopathy (DR), which is a complication of DM, are on the rise. AIM: To analyze early DR in patients with macular zone changes in biological images using optical coherence tomography angiography. METHODS: A prospective case study was performed on 59 participants: 35 healthy eyes (control group), 35 eyes with diabetes but no DR group (no DR group), and 35 eyes with mild DR (NPDR group). All quantitative comparisons of parameters, including the fovea vascularity area, circularity index, and vascular complexity parameters, were performed using a biological image analysis software. RESULTS: The foveal avascular zone (FAZ) area, FAZ circularity index, number of branches in the area, and the total of the single branches' length in the area was 0.366 ± 0.031, 0.834 ± 0.037, 3241.8 ± 268.3, and 3.860 × 107 ± 0.194 × 107, and 0.421 ± 0.030, 0.739 ± 0.023, 2956.6 ± 476.4, and 3.177 × 107 ± 0.161 × 107 in the no DR group and the NPDR group, respectively, which were significantly different from the corresponding parameters of the control group (P < 0.05). Moreover, there were significant differences between these two groups (P < 0.05). CONCLUSION: This study shows that early microcirculation changes in the macular area of the retina is associated with disease progression. Early changes in DR can be analyzed using optical coherence tomography angiography.

Deep anterior lamellar keratoplasty with cross-linked acellular porcine corneal stroma to manage fungal keratitis.

PURPOSE: To evaluate the effects of deep anterior lamellar keratoplasty (DALK) with cross-linked acellular porcine corneal stroma (APCS) and post-operative topical tacrolimus treatment in patients with fungal keratitis. METHODS: This multicenter prospective study involved 25 cases of fungal keratitis that were treated by DALK with cross-linked APCSs and post-operative topical tacrolimus from December 2013 to November 2014 at the Wenzhou Eye Hospital and the Henan provincial Eye Hospital. Signs of post-operative inflammation, corneal reepithelialization, corneal neovascularization, and graft rejection were assessed, and best corrected visual acuity (BCVA), intraocular pressure (IOP), and APCS graft transparency were monitored for the 12-month follow-up period. RESULTS: All 25 patients underwent DALK without Descemet's membrane perforation. Corneal epithelium recovered completely in 17 patients in the first week, and APCS grafts maintained transparency in 18 patients at 1-year follow-up. The mean BCVA significantly improved from 2.16 ± 0.32 (LogMAR) at baseline to 1.56 ± 0.70 at 1-week (P < .001), 0.95 ± 0.57 at 1-month (P < .001), and 0.70 ± 0.51 at 3-month follow-ups (P < .001). The BCVA kept stable at 6-month and 12-month follow-ups. Post-operative topical tacrolimus alleviated the ciliary injection, except in one case which acute stromal rejection occurred. One patient developed fungal reinfection and underwent penetrating keratoplasty. Graft rejection occurred in three patients. No case was noted with graft splitting, elevated IOP or tacrolimus intolerance. CONCLUSIONS: DALK using cross-linked APCS combining topical tacrolimus treatment is safe and effective in managing fungal keratitis. It may ameliorate the shortage of corneal donation globally.

Can groundwater be protected from the pressure of china's urban growth?

Groundwater is expected to be more vulnerable to water-quality degradation in the future due to rapid urbanization. However, despite knowledge that protecting future groundwater resources is necessary for sustainable groundwater resource development, little is known about the role of groundwater policy in influencing the spatial distribution of urbanization. This study sheds light on how a policy that protects vulnerable groundwater could affect the distribution of urban expansion. Groundwater vulnerability to pollution under future climate change scenarios is used as a factor to generate urban expansion probability maps for China. The results indicate that there will be a significant and uneven urban growth by 2030, if current trends in urban expansion continue. The amount of urban land in 2030 will range from 2.9 to 4.2 times the urban area in 2010. Meanwhile, the urban expansion probability maps for projections with and without consideration of groundwater vulnerability in urban suitability are compared. The comparation shows that consideration of a groundwater policy would significantly alter the future spatial distribution of urban areas. Even with a weight of only 10% for groundwater vulnerability in the urban suitability consideration, the percentage of change area in the urban expansion probability distribution map can be as high as 60%. The probabilities of urban expansion are forecast to gradually transfer from the southeast coastal areas to inland areas as higher weight (from 10% to 50%) of groundwater vulnerability is given to urban suitability consideration. Our study demonstrates that groundwater protection from urbanization pressures can be achieved, provides support for policy and decision makers in evaluating options to modify existing urban expansion policies, and concludes that groundwater protection at the macro-scale is an appropriate policy goal.

Optimization of management strategies for reducing nitrogen loading in China.

Terrestrial Nitrogen (N) loading in the environment has seen a steady increase over the past several decades as a result of more intensive anthropogenic activities. Quantifying N loading for an extended period is important for effective N management. In this study, a statistical model is constructed to describe the relationship between N loading and anthropogenic activities at watershed scale for 211 watersheds covering the entire land area of China. Subsequently, a portfolio optimization model is used to optimize the future management efforts of the long-term N loading. Our results show that N loading in China due to anthropogenic activities has increased significantly over the past 60 years (1949-2010), with the rate of increase at approximately 1 Tg N/year. When designing future N loading management strategies, the next 30 years is divided into three temporal stages and assume that the total amount of expenditure is fixed. The results of portfolio optimization analysis show that the best allocations of management efforts (e.g. capital investments, making new policies, improving technology, or alike) among three temporal stages are 28.55% (2021-2030), 71.45% (2031-2040) and 0 (2041-2050). Furthermore, it is suggested that the future population growth scenario has the largest influence on the results of the portfolio optimization analysis.

Coupling Modern Portfolio Theory and Marxan enhances the efficiency of Lesser White-fronted Goose's (Anser erythropus) habitat conservation.

Climate change and human activities cause uncertain changes to species biodiversity by altering their habitat. The uncertainty of climate change requires planners to balance the benefit and cost of making conservation plan. Here optimal protection approach for Lesser White-fronted Goose (LWfG) by coupling Modern Portfolio Theory (MPT) and Marxan selection were proposed. MPT was used to provide suggested weights of investment for protected area (PA) and reduce the influence of climatic uncertainty, while Marxan was utilized to choose a series of specific locations for PA. We argued that through combining these two commonly used techniques with the conservation plan, including assets allocation and PA chosing, the efficiency of rare bird's protection would be enhanced. In MPT analyses, the uncertainty of conservation-outcome can be reduced while conservation effort was allocated in Hunan, Jiangxi and Yangtze River delta. In Marxan model, the optimal location for habitat restorations based on existing nature reserve was identified. Clear priorities for the location and allocation of assets could be provided based on this research, and it could help decision makers to build conservation strategy for LWfG.

Cross-linked decellularized porcine corneal graft for treating fungal keratitis.

This study aims to develop a cross-linked decellularized porcine corneal graft (cDPC) as a substitute for lamellar donor corneas and to evaluate the feasibility of using cDPC to treat fungal keratitis. The cDPC was prepared by decellularization, chemical crosslinking and γ-ray irradiation. Transparency, effectiveness of decellularization and biomechanical strength of cDPC were evaluated. The safety and efficacy of using cDPC to treat fungal keratitis were evaluated in the rabbit model. The transparency of cDPC was similar to that of a native porcine cornea (NPC), and no intact cells were observed in cDPC except for an insignificant amount of residual shrinking cellular nucleus. Compared to the NPC, the biomechanical strength of the cDPC was significantly increased. In the rabbit model of lamellar keratoplasty, the implanted cDPC reduced the incidence of corneal perforation, and also maintained transparency in majority. The results of this study suggest that the cDPC is capable of restoring the original transparency of cornea while effectively treating fungal keratitis. The cDPC is a highly promising ideal substitute for the donor human cornea.

Effect of exercise on cognitive function in chronic disease patients: a meta-analysis and systematic review of randomized controlled trials.

BACKGROUND: The purpose of this study was to conduct a meta-analysis and systematic review to assess the effect of exercise on cognitive function in people with chronic diseases. METHODS: PubMed, Web of Science, Embase, the Cochrane Library, CINAHL, PsycINFO, and three Chinese databases were electronically searched for papers that were published until September 2016. This meta-analysis and systematic review included randomized controlled trials that evaluated the effect of exercise on cognitive function compared with control group for people with chronic diseases. RESULTS: Totally, 35 studies met the inclusion criteria, with 3,113 participants. The main analysis revealed a positive overall random effect of exercise intervention on cognitive function in patients with chronic diseases. The secondary analysis revealed that aerobic exercise interventions and aerobic included exercise interventions had a positive effect on cognition in patients with chronic diseases. The intervention offering low frequency had a positive effect on cognitive function in patients with chronic diseases. Finally, we found that interventions offered at both low exercise intensity and moderate exercise intensity had a positive effect on cognitive function in patients with chronic diseases. The secondary analysis also revealed that exercise interventions were beneficial in Alzheimer's disease patients when grouped by disease type. CONCLUSION: This meta-analysis and systematic review suggests that exercise interventions positively influence cognitive function in patients with chronic diseases. Beneficial effect was independent of the type of disease, type of exercise, frequency, and the intensity of the exercise intervention.

Risk management for optimal land use planning integrating ecosystem services values: A case study in Changsha, Middle China.

Land-use change has direct impact on ecosystem services and alters ecosystem services values (ESVs). Ecosystem services analysis is beneficial for land management and decisions. However, the application of ESVs for decision-making in land use decisions is scarce. In this paper, a method, integrating ESVs to balance future ecosystem-service benefit and risk, is developed to optimize investment in land for ecological conservation in land use planning. Using ecological conservation in land use planning in Changsha as an example, ESVs is regarded as the expected ecosystem-service benefit. And uncertainty of land use change is regarded as risk. This method can optimize allocation of investment in land to improve ecological benefit. The result shows that investment should be partial to Liuyang City to get higher benefit. The investment should also be shifted from Liuyang City to other regions to reduce risk. In practice, lower limit and upper limit for weight distribution, which affects optimal outcome and selection of investment allocation, should be set in investment. This method can reveal the optimal spatial allocation of investment to maximize the expected ecosystem-service benefit at a given level of risk or minimize risk at a given level of expected ecosystem-service benefit. Our results of optimal analyses highlight tradeoffs between future ecosystem-service benefit and uncertainty of land use change in land use decisions.

Effects of heavy metals and soil physicochemical properties on wetland soil microbial biomass and bacterial community structure.

Heavy metals (HMs) contamination is a serious environmental issue in wetland soil. Understanding the micro ecological characteristic of HMs polluted wetland soil has become a public concern. The goal of this study was to identify the effects of HMs and soil physicochemical properties on soil microorganisms and prioritize some parameters that contributed significantly to soil microbial biomass (SMB) and bacterial community structure. Bacterial community structure was analyzed by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE). Relationships between soil environment and microorganisms were analyzed by correlation analysis and redundancy analysis (RDA). The result indicated relationship between SMB and HMs was weaker than SMB and physicochemical properties. The RDA showed all eight parameters explained 74.9% of the variation in the bacterial DGGE profiles. 43.4% (contain the variation shared by Cr, Cd, Pb and Cu) of the variation for bacteria was explained by the four kinds of HMs, demonstrating HMs contamination had a significant influence on the changes of bacterial community structure. Cr solely explained 19.4% (p<0.05) of the variation for bacterial community structure, and Cd explained 17.5% (p<0.05), indicating Cr and Cd were the major factors related to bacterial community structure changes.

How to manage future groundwater resource of China under climate change and urbanization: An optimal stage investment design from modern portfolio theory.

Groundwater management in China has been facing challenges from both climate change and urbanization and is considered as a national priority nowadays. However, unprecedented uncertainty exists in future scenarios making it difficult to formulate management planning paradigms. In this paper, we apply modern portfolio theory (MPT) to formulate an optimal stage investment of groundwater contamination remediation in China. This approach generates optimal weights of investment to each stage of the groundwater management and helps maximize expected return while minimizing overall risk in the future. We find that the efficient frontier of investment displays an upward-sloping shape in risk-return space. The expected value of groundwater vulnerability index increases from 0.6118 to 0.6230 following with the risk of uncertainty increased from 0.0118 to 0.0297. If management investment is constrained not to exceed certain total cost until 2050 year, the efficient frontier could help decision makers make the most appropriate choice on the trade-off between risk and return.

iTRAQ-Based Proteomic Analysis of Visual Cycle-Associated Proteins in RPE of rd12 Mice before and after RPE65 Gene Delivery.

Purpose. To investigate the iTRAQ-based proteomic changes of visual cycle-associated proteins in RPE of rd12 mice before and after RPE65 gene delivery. Mehtods. The right eyes of rd12 mice underwent RPE65 gene delivery by subretinal injection at P14, leaving the left eyes as control. C57BL/6J mice were served as a wide-type control group. ERGs were recorded at P42, and RPE-choroid-sclera complex was collected to evaluate the proteomic changes in visual cycle-associated proteins by iTRAQ-based analysis. Western blot was used to confirm the changes in the differentially expressed proteins of interest. Results. ERG parameters improved dramatically at P42 after RPE65 delivery. The proteomics analysis identified a total 536 proteins with a global false discovery rate of 0.21%, out of which 7 were visual cycle-associated proteins. RALBP-1, RBP-1, and IRBP were reduced in the untreated rd12 eyes and the former two were improved after gene therapy, confirmed by Western blot analysis. Conclusions. RPE65 gene delivery restored retinal function at P42 and modified the expression of other functional proteins implicated in the visual cycle. The level of RALBP-1 was still below the normal level after gene therapy in rd12 mice, which may explain the delayed dark adaption in LCA patients undergoing similar therapy.

An integrated model for assessing heavy metal exposure risk to migratory birds in wetland ecosystem: A case study in Dongting Lake Wetland, China.

Heavy metal contamination is present in wetland ecosystem worldwide, and quantitative risk assessment model is significant. In this study, an exposure model was integrated for assessing heavy metal exposure risk to migratory birds in Dongting Lake Wetland (DTW). The concentrations of Cr, Cu, Pb, Cd, Hg and As in water, plant, soil and fish were investigated from 9 migratory bird habitats. The results showed that exposure doses from drinking water pathways were very low. There was a sensitive area that Cd and As exposure doses exceeded the most conservative tolerable daily intake, which is located at the estuary of Xiang River. In general, Dunlin had a greater risk than Eurasian Spoonbill. Hg, Pb and Cr were likely to have adverse effect on carnivorous migrants in DTW, while Cu and Cd were considered to be relatively safe. Almost all heavy metals were at no risk for Lesser White-fronted Goose in DTW.

Dynamic ocular surface and lacrimal gland changes induced in experimental murine dry eye.

Dry eye disease can be a consequence of lacrimal gland insufficiency in Sjögren's Syndrome or increased tear film evaporation despite normal lacrimal gland function. To determine if there is a correlation between severity effects in these models and underlying pathophysiological responses, we compared the time dependent changes in each of these parameters that occur during a 6 week period. Dry eye was induced in 6-week-old female C57BL/6 mice by exposing them to an Intelligently Controlled Environmental System (ICES). Sixty mice were housed in ICES for 1, 2, 4 and 6 weeks respectively. Twelve were raised in normal environment and received subcutaneous injections of scopolamine hydrobromide (SCOP) 3 times daily for 5 days. Another sixty mice were housed in a normal environment and received no treatment. Corneal fluorescein staining along with corneal MMP-9 and caspase-3 level measurements were performed in parallel with the TUNEL assay. Interleukin-17(IL-17), IL-23, IL-6, IL-1, TNF-α, IFN-γ and TGF-ß2 levels were estimated by real-time PCR measurements of conjunctival and lacrimal gland samples (LGs). Immunohistochemistry of excised LGs along with flow cytometry in cervical lymph nodes evaluated immune cell infiltration. Light and transmission electron microscopy studies evaluated LGs cytoarchitectural changes. ICES induced corneal epithelial destruction and apoptosis peaked at 2 weeks and kept stable in the following 4 weeks. In the ICES group, lacrimal gland proinflammatory cytokine level increases were much lower than those in the SCOP group. In accord with the lower proinflammatory cytokine levels, in the ICES group, lacrimal gland cytosolic vesicular density and size exceeded that in the SCOP group. ICES and SCOP induced murine dry eye effects became progressively more severe over a two week period. Subsequently, the disease process stabilized for the next four weeks. ICES induced local effects in the ocular surface, but failed to elicit lacrimal gland inflammation and cytoarchitectural changes, which accounts for less dry eye severity in the ICES model than that in the SCOP model.

Reactive oxygen species activated NLRP3 inflammasomes prime environment-induced murine dry eye.

Tear film hyperosmolarity along with exposure to oxidant stress are factors that can induce chronic ocular surface inflammation and pain. However, there is limited information on how increases in reactive oxygen species (ROS) generated by oxidant exposure can induce inflammation. There is emerging evidence in other tissues that innate immune responses to a variety of environmental stresses stem from ROS-induced cytosolic NLRP3 inflammasome activation. Once this occurs, pro-caspase-1 is converted into its catalytic active form, which in turn cleaves pro-IL-1ß thereby generating its bioactive form. We determined the role of ROS generation in mediating increases in IL-1ß secretion through caspase-1 activation caused by NLRP3 inflammasome activation in an environment-induced murine dry eye (DE) model. An intelligently controlled environmental system (ICES) induced evaporative DE in female 4-6 week old C57BL/6J mice. Increases in ROS production preceded rises in corneal and conjunctival gene expression of NLRP3 inflammasome components and IL-1ß that were identified using real-time PCR. Confocal microscopy evaluated concomitant increases in NLPR3, caspase-1 and IL-1ß immunostaining. Increases in caspase-1 activity were used as an indicator of inflammasome activation. Rises in ROS generation occurred after 1 week of ICES exposure, which preceded increases in gene expression of three NLRP3 inflammasome components (i.e. NLRP3, ASC and caspase-1) leading to rises in bioactive IL-1ß release. Increases in caspase-1 activity occurred after 2 weeks of ICES exposure. Eyedrops containing 0.3% N-acetyl-l-cysteine (NAC) were applied to quench ROS generation by mice kept in the ICES for 2 weeks. This scavenger reduced corneal fluorescein staining and decreased ROS production. NAC also down-regulated both increases in NLRP3, ASC, caspase-1 and IL-1ß mRNA levels, along with their immunostaining. It robustly attenuated rises in inflammasome mediated increases in caspase-1 catalytic activity. We show in a dessicating DE disease murine model that rises in ROS generation trigger NLRP3 inflammasome complexation and activation leading to increases in bioactive IL-1ß secretion. These results prompt us to suggest that the ROS-NLRP3-IL-1ß signaling pathway might play a priming role in environment-induced DE progression. Finally, our findings provide a basis for developing novel strategies that may improve the management of patients requiring treatment for environment-induced dry eye disease.