[Research progress on anti-atherosclerosis effect and mechanism of flavonoids compounds mediated by macrophages].

Flavonoids are important active ingredients of traditional Chinese medicine, mainly with cardiovascular, anti-liver injury, antioxidant, antispasmodic, and estrogen-like effects. These compounds have obvious effects on the cardiovascular and cerebrovascular diseases. Macrophage-derived foam cells are the key medium in the process of atherosclerosis(AS). In plaque, allserum lipids, serum lipoproteins, and various pro-or anti-inflammatory stimulating factors, chemokines, and small bioactive molecules can significantly affect the macrophage phenotype and induce stronger pro-inflammatory or anti-inflammatory properties. Studies have shown that some flavonoids can be used for macrophages through different pathways and mechanisms, playing an anti-atherosclerosis effect to different degrees, including promotion of cholesterol efflux from macrophages, anti-foaming of macrophages, inhibition of secretion of inflammatory factors, and antioxidant modified low density lipoprotein(ox-LDL)-induced apoptosis of macrophages. Related gene regulation inclu-ded ATP-binding cassette transporter A1(ABCA1), ATP-binding cassette transporter G1(ABCG1), Toll-like receptor(TLR), and scavenger receptor(SR). In this article, we would review the recent research progress of flavonoids on anti-atherosclerosis effect me-diated by macrophage. It is expected to provide new treatment strategies for AS-related cardiovascular and cerebrovascular diseases, and provide research ideas and development directions for the use of related natural medicines and design of new products.

The Secreted Protein MoHrip1 Is Necessary for the Virulence of Magnaporthe oryzae.

Secreted effectors from Magnaporthe oryzae play critical roles in the interaction with rice to facilitate fungal infection and disease development. M. oryzae-secreted protein MoHrip1 can improve plant defense as an elicitor in vitro, however, its biological function in fungal infection is not clear. In this study, we found that the expression of mohrip1 was significantly induced in the stages of fungal penetration and colonization. Although dispensable for the growth and conidiation, MoHrip1 was necessary for the full virulence of M. oryzae. Deletion of mohrip1 remarkably compromised fungal virulence on rice seedlings and even on rice leaves with wounds. Rice sheath inoculation assay further demonstrated the defects of mohrip1-deleted mutants on penetration and proliferation in rice cells. Additionally, compared with WT and complementation strain, the inoculation of mohrip1-deleted mutants induced a higher expression of specific defense related genes and a higher production of specific defensive compounds in rice leaves. These data collectively indicated that MoHrip1 is necessary for fungal penetration and invasive expansion, and further full virulence of rice blast fungus.

[Effect of germacrone in alleviating HUVECs damaged by H2O2-induced oxidative stress].

This study focuses on the protective effect of germacrone on human umbilical vein endothelial cells(HUVECs) damaged by H2O2-induced oxidative stress and its possible mechanisms. The oxidative damage model was established by using 500 µmol•L⁻¹ H2O2 to treat HUVECs for 3 hours, and then protected with different concentrations of germacrone for 24 hours. The effect of germacrone on cell viability of HUVECs damaged by H2O2 was detected by MTT. The contents of PGI2, TXB2, ET-1, t-PA, PAI-1, TNF-α and IL-6 were detected by ELISA. The content of NO was detected by using nitrate reductase method. Colorimetry was used to detect NOS and GSH-Px. The contents of MDA, SOD and LDH were detected by TBA, WST-1 and microplate respectively. Apoptosis was observed by Hoechst 33258 fluorescent staining. The mRNA expressions of Bax, Bcl-2 and Caspase-3 in cells were detected by RT-PCR. The results showed that the cell damage rate was 52% after treated with 500 µmol•L⁻¹ H2O2 for 3 hours. The cell activity was increasing with the rise of germacrone concentration within the range of 20-200 mol•L⁻¹. Compared with normal group, the contents of PGI2, NO, T-NOS, t-PA, SOD, GSH-Px and Bcl-2 mRNA expressions were lower after damaged with H2O2. The contents of PAI-1, ET-1, IL-6, TNF-α, TXB2, LDH, MDA, Bax mRNA and Caspase-3 mRNA expressions were increased. Compared with model group, the contents of PGI2, NO, T-NOS, t-PA, SOD, GSH-Px and Bcl-2 mRNA expressions were increased after treated with germacrone. The contents of PAI-1, ET-1, IL-6, TNF-α, TXB2, LDH, MDA, Bax mRNA and Caspase-3 mRNA expressions were lower after treated with germacrone. According to Hoechst 33258 fluorescence staining, compared with normal group, the cell membrane and the nucleus showed strong dense blue fluorescence, and the number of cells significantly decreased in model group. Compared with model group, blue fluorescence intensity decreased in drug group. The above findings demonstrate that germacrone may improve the effect on HUVECs damaged by H2O2-induced oxidative stress by resisting oxidation and inhibiting cell apoptosis.

Inducible and constitutive expression of an elicitor gene Hrip1 from Alternaria tenuissima enhances stress tolerance in Arabidopsis.

Hrip1 is a novel hypersensitive response-inducing protein secreted by Alternaria tenuissima that activates defense responses and systemic acquired resistance in tobacco. This study investigates the role that Hrip1 plays in responses to abiotic and biotic stress using transgenic Arabidopsis thaliana expressing the Hrip1 gene under the control of the stress-inducible rd29A promoter or constitutive cauliflower mosaic virus 35S promoter. Bioassays showed that inducible Hrip1 expression in rd29A∷Hrip1 transgenic lines had a significantly higher effect on plant height, silique length, plant dry weight, seed germination and root length under salt and drought stress compared to expression in 35S∷Hrip1 lines and wild type plants. The level of enhancement of resistance to Botrytis cinerea by the 35S∷Hrip1 lines was higher than in the rd29A∷Hrip1 lines. Moreover, stress-related gene expression in the transgenic Arabidopsis lines was significantly increased by 200 mM NaCl and 200 mM mannitol treatments, and defense genes in the jasmonic acid and ethylene signaling pathway were significantly up-regulated after Botrytis inoculation in the Hrip1 transgenic plants. Furthermore, the activity of some antioxidant enzymes, such as peroxidase and catalase increased after salt and drought stress and Botrytis infection. These results suggested that the Hrip1 protein contributes to abiotic and biotic resistance in transgenic Arabidopsis and may be used as a useful gene for resistance breeding in crops. Although the constitutive expression of Hrip1 is suitable for biotic resistance, inducible Hrip1 expression is more responsive for abiotic resistance.

Association of C(-106)T polymorphism in aldose reductase gene with diabetic retinopathy in Chinese patients with type 2 diabetes mellitus.

OBJECTIVE: To identify the possible association between C(-106)T polymorphism of the aldose reductase (ALR) gene and diabetic retinopathy (DR) in a cohort of Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: From November 2009 to September 2010, patients with T2DM were recruited and assigned to DR group or diabetic without retinopathy (DWR) group according to the duration of diabetes and the grading of 7-field fundus color photographs of both eyes. Genotypes of the C(-106)T polymorphism (rs759853) in ALR gene were analyzed using the MassARRAY genotyping system and an association study was performed. RESULTS: A total of 268 T2DM patients (129 in the DR group and 139 in the DWR group) were included in this study. No statistically significant differences were observed between the 2 groups in the age of diabetes onset (P=0.10) and gender (P=0.78). The success rate of genotyping for the study subjects was 99.6% (267/268), with one case of failure in the DR group. The frequencies of the T allele in the C(-106)T polymorphism were 16.0% (41/256) in the DR group and 19.4% (54/278) in the DWR group (P=0.36). There was no significant difference in the C(-106)T genotypes between the 2 groups (P=0.40). Compared with the wild-type genotype, odds ratio (OR) for the risk of DR was 0.7 (95% CI, 0.38-1.3) for the heterozygous CT genotype and 0.76 (95% CI, 0.18-3.25) for the homozygous TT genotype. The risk of DR was positively associated with microalbuminuria (OR=4.61; 95% CI, 2.34-9.05) and insulin therapy (OR=3.43; 95% CI, 1.94-6.09). CONCLUSIONS: Microalbuminuria and insulin therapy are associated with the risk of DR in Chinese patients with T2DM. C(-106)T polymorphism of the ALR gene may not be significantly associated with DR in Chinese patients with T2DM.

[Effects of xuefu zhuyu decoction on antioxidant and drug-metabolizing enzymes in liver of rats].

Xuefu Zhuyu decoction (XFZYD) is a famous traditional Chinese medicine (TCM) formula, is widely used in the treatment of cardiovascular and cerebrovascular diseases in China over one hundred years. But its effect on antioxidant and drug-metabolizing enzymes are unknown. This study was to observe the effects of Xuefu Zhuyu decoction (XFZYD) on the activities of antioxidant and drug metabolism enzymes (DMEs) in liver of rats. Male SD rats, treated with XFZYD at the dosage of 3.51, 7.02 and 14.04 g x kg(-1) per day for 15 days, serum were collected, tissue fluid, cytosols and microsomes isolated from liver tissues were prepared by centrifugation according to the standard procedure, the activities of antioxidant enzymes and drug-Metabolizing Enzymes were determined by UV-V is spectrophotometer. In serum, the activities of AST was not significantly affected by the treatment with XFZYD, at the high- est dose, the levels of ALT, Cr and BUN were significantly decreased (P < 0.05). GPX were significantly increased at the dose of 7.02, 14.04 g x kg(-1) (P < 0.05), CAT were significantly increased at the highest dose (P < 0.05). T-SOD was not significantly af- fected by this treatment. In the liver tissue, GPX was significantly increased at the dose of 3.51, 7.02 g x kg(-1) (P < 0.05), GST, CAT and T-SOD were not significantly affected following this treatment. In cytosols, GST was significantly increased at the dose of 3.51 g x kg(-1) (P < 0.05), T-SOD was remarkable induced at the dose of 3.51 and 7.02 g x kg(-1) (P < 0.05). In microsomes, XFZYD had no significant effect on Cytochromeb5, NADPH-Cytochrome P450 reductase, CYP3A, CYP2E1 and UGT, XFZYD significantly in- duced GST at the dose of 3.51 and 7.02 g x kg(-1) (P < 0.05), and the level of GSH were significantly increased by XFZYD at the dose of 3.51, 7.02 and 14.04 g kg(-1) (P < 0.05). These findings suggest XFZYD can induce the activities of GPX, CAT, SOD, GST and increase GSH level in liver of rats, which indicate XFZYD may have detoxification and antioxidant functions.

Self-management theories, models and frameworks in patients with chronic heart failure: A scoping review.

AIM: The aim of this study was to synthesize the self-management theory, model and frameworks of patients with chronic heart failure, focusing on construction process, methods and existing problems. BACKGROUND: Although the self-management theories have been created and verified for those patients with chronic heart failure, no reviews have been performed to integrate these theories. DESIGN: A scoping review of recent literature (without a date limit) was conducted. METHODS: A comprehensive literature search was performed. If the study reported the construction of a self-management theory, model or framework about chronic heart failure cases, it would be included in the review. RESULTS: Fourteen studies were included, which could be categorized into situation-specific theory, middle-range theory and other theory models (including conceptual model, hypothetic regression model and identity description model). It also includes the update and validation of theories, the situation-specific theoretical of caregiver contributions extended from situation-specific theories and the nurse-led situation-specific theory in different contexts. CONCLUSION: Self-management might contribute to start an education programme before patients with chronic heart failure (CHF) begin their chronic disease live as an individual. Our scoping review indicates that a series of self-management theories, models and frameworks for CHF patients have been developed, but more studies are still needed to validate and support these theories according to their cultural contexts.

[Association of single nucleotide polymorphism in complement factor I gene with age-related macular degeneration].

OBJECTIVE: To investigate the association of three single nucleotide polymorphism (SNP) in the upstream of the complement factor I (CFI) gene with age-related macular degeneration (AMD) in a Chinese population. METHODS: Case-control study. Patients with early or late stages of AMD and healthy control subjects were recruited. Genomic DNA was extracted from the peripheral venous blood. Genotyping for SNP rs10033900: T > C, rs13117504: C > G and rs2285714: C > T in the upstream of the CFI gene was determined by using a method of polymerase chain reaction (PCR) followed by restriction enzyme digestion and direct sequencing. Statistical analysis was performed using the R statistical analysis package. RESULTS: A total of three hundreds and seventy nine participants were enrolled in the study, including 119 patients with exudative AMD, 120 patients with early AMD and 140 control individuals without AMD. Frequency of the minor allele C of rs10033900 in exudative AMD, early AMD and control groups were 17.4% (40/230), 22.5% (54/240) and 29.3% (82/280), respectively. Significant association of rs10033900 was detected with exudative AMD (χ(2) = 9.82, P = 0.002, OR = 0.57, 95%CI: 0.36 - 0.88), but not with early AMD (χ(2) = 3.08, P = 0.079). Frequency of the minor allele G of rs13117504 in exudative AMD, early AMD and control groups were 38.6% (91/236), 54.2% (130/240) and 51.8% (145/280), respectively. Significant association of rs13117504 was detected with exudative AMD (χ(2) = 9.03, P = 0.003, OR = 0.56, 95%CI: 0.39 - 0.82), but not with early AMD (χ(2) = 0.29, P = 0.59). No association was detected between rs2285714 and exudative AMD (χ(2) = 0.72, P = 0.31) or between rs2285714 and early AMD (χ(2) = 2.30, P = 0.13). CONCLUSION: The minor allele of rs10033900 and rs13117504 in the CFI gene may have a protective role against the risk of exudative AMD.

[Relationship of angiotensin converting enzyme gene polymorphism with diabetic retinopathy].

OBJECTIVE: To investigate the association between angiotensin converting enzyme (ACE) gene locus rs1799752 insertion/deletion (I/D) polymorphism and diabetic retinopathy (DR) in type 2 diabetes mellitus. METHODS: Case-control study. Type 2 diabetes patients were recruited and assigned into DR group, which included proliferative diabetic retinopathy (PDR) group or diabetes without retinopathy (DWR) group. Volunteers without diabetes from the same community were recruited as the control group. PCR and agarose gel electrophoresis methods were adopted to determine the rs1799752 I/D polymorphism genotypes of the ACE gene. The frequency of genotypes and alleles was compared among the various groups. RESULTS: Four hundred and twelve diabetes patients: (207 subjects of DR, including 53 subjects of PDR and 205 subjects of DWR) and 97 non-diabetic control subjects were included in the study. The frequencies of the I and D alleles of ACE rs1799752 polymorphism were 54.1% and 45.9%, respectively, in the DR group, 52.8% and 47.2% in the PDR group, and 48.0% and 52.0% in the DWR group. There were no statistical differences between DR and DWR groups (χ(2) = 3.02, P > 0.05) or between PDR and DWR groups (χ(2) = 0.77, P > 0.05). Moreover, there were no statistical differences in the distribution of the ACE genotypes between DR group (II 25.1%, ID 58.0%, DD 16.9%) and DWR group (II 22.0%, ID 52.2%, DD 25.9%) (χ(2) = 4.92, P > 0.05) or between PDR group (II 20.7%, ID 64.2%, DD 15.1%) and DWR group (χ(2) = 3.19, P > 0.05). No statistical differences were found in the frequencies of the I and D alleles, and the distributions of I/D genotypes between diabetic group and the control group (χ(2) = 0.25, 4.98; P > 0.05). In the multiple regressions model including clinical factors such as the age of onset of diabetes, urinary albumin, insulin usage, creatinine, glycated hemoglobin, fast glucose, and the use of ACE inhibitor, no association was found between ACE gene polymorphism and DR (OR = 0.80, 95%CI: 0.59 - 1.09) or PDR (OR = 1.23, 95%CI: 0.78 - 1.93). CONCLUSION: There is no association between ACE rs1799752 gene insertion/deletion (I/D) polymorphism and DR in patients with type 2 diabetes mellitus.

[Diabetes self-management and its association with diabetic retinopathy in patients with type 2 diabetes].

OBJECTIVE: To investigate the association of diabetic self-management with the risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus. METHODS: Cross-sectional study. Recruited patients with type 2 diabetes mellitus in the Desheng community of urban Beijing between November 2009 and May 2011. All patients were surveyed using a standardized questionnaire and underwent detailed ophthalmic examination. Patients were classified into DR group or diabetic without retinopathy (DWR) group according to the grading of fundus color photographs using the Early Treatment of Diabetic Retinopathy Study (ETDRS) standard grading protocol. In the DR group, proliferative diabetic retinopathy (PDR) was further defined. The overall levels of diabetes self-management in the study population were assessed and compared for the differences between DR and DWR, PDR and NPDR groups. RESULTS: One thousand one hundred patients with type 2 diabetes mellitus were recruited. The prevalence of DR was 32.1% (353/1100) in the study population. Sixty-three percent (652/1035) of patients had glycated hemoglobin (HbA1c) level less than 7.0%. The majority of patients (85.4%, 916/1072) conducted a diet control, 77.3% (827/1070) exercised, 56.0% (609/1088) monitored blood glucose regularly, 56.8% (416/733) detected HbA1c more than once every six months, 71.7% (762/1062) had ophthalmologic examination after the diagnosis of diabetes mellitus, and 47.9% (525/1097) had mydriatic check-up. Increased risk of DR was associated with longer duration of diabetes (more than 10 years) (OR = 3.90, 95% CI:2.97-5.51, P < 0.05), higher HbA1c level of ≥ 7.0% (OR = 3.23, 95% CI:2.44-4.28, P < 0.05), insulin therapy (OR = 4.82, 95% CI:3.55-6.57, P < 0.05), male gender (OR = 1.41, 95% CI:1.08-1.84, P < 0.05), lower level of education (OR = 1.90, 95% CI:1.39-2.62, P < 0.05), lower monthly income (OR = 1.46, 95% CI:1.12-1.91, P < 0.05), lower obedience to diet control (OR = 1.72, 95% CI:1.22-2.43, P < 0.05), no exercise (OR = 1.42, 95% CI:1.04-1.94, P < 0.05), change of therapeutic protocol during the last five years (OR = 1.78, 95% CI:1.32-2.41, P < 0.05), and family history of diabetes (OR = 1.35, 95% CI:1.01-1.78, P < 0.05). Increased risk of PDR was associated with the diagnosis age of diabetes (OR = 0.92, 95% CI:0.89-0.95, P < 0.05), longer duration of diabetes (more than 10 years) (OR = 4.54, 95% CI:1.95-12.32, P < 0.05), and insulin therapy (OR = 4.85, 95% CI:2.34-10.90, P < 0.05). In the multifactor logistic regression model, male gender (OR = 2.21, 95% CI:1.57-3.11, P < 0.05), lower level of education (OR = 1.98, 95% CI:1.33-2.94, P < 0.05), lower monthly income (OR = 1.66, 95% CI:1.15-2.39, P < 0.05) ,longer duration of diabetes (more than 10 years) (OR = 2.46, 95% CI:1.77-3.41, P < 0.05) ,HbA1c ≥ 7.0% (OR = 2.24, 95% CI:1.64-3.07, P < 0.05) and insulin therapy (OR = 3.38, 95% CI:2.38-4.8, P < 0.05) were associated with higher risk of DR. The diagnosis age of diabetes (OR = 0.94, 95% CI:0.91-0.98, P < 0.05) and insulin therapy (OR = 3.49, 95% CI:1.47-8.27, P < 0.05) were associated with PDR. CONCLUSION: Higher risk of DR is associated with longer duration of diabetes,insulin therapy, higher HbA1c level, male gender, and lower level of education, whereas higher risk of DR is also associated with lower obedience to diet control and less exercise, which suggest that lower level of diabetic self-management increased the risk of DR.

An insecticidal protein from Xenorhabdus budapestensis that results in prophenoloxidase activation in the wax moth, Galleria mellonella.

Xenorhabdus budapestensis can produce a variety of proteins that help this bacterium and its mutualistic nematode vector kill the host insect. In this report, we purified one protein fraction from the intracellular extract of X. budapestensis D43, which was designated HIP57. By injection, HIP57 caused Galleria mellonella larval bodies to blacken and die with an LD(50) of 206.81 ng/larva. Analyzes of HIP57 by two-dimensional gel electrophoresis showed that this protein was a single spot on the gel with a molecular weight of 57 kDa and a pI of ∼5. Sequencing and bioinformatic analysis suggested that the HIP57 toxin was homologous to GroEL. GroEL has been accepted as molecule chaperon; however, our research revealed that HIP57 (GroEL) possesses another novel function as an insecticide. A GroEL phylogenetic tree defined the relationship among the related species of mutualistic bacteria (Xenorhabdus and Photorhabdus) from the entomopathogenic nematodes and the evolution within the family Enterobacteriaceae. Thus, GroEL could be a complement to 16S rDNA for studying the molecular phylogenies of the family Enterobacteriaceae. Phenoloxidase (PO) activity analysis of G. mellonella larvae injected with HIP57 suggested that the toxin activates the PO cascade, which provides an extensive defense reaction that potentially responsible for G. mellonella larval death.

[Inhibitory effect of PNS on drug metabolism enzyme CYP3A in rat livers and its kinetic analysis].

OBJECTIVE: To study the inhibitory effect of total saponins of the root and rhizome of Panax notoginseng (PNS) on drug metabolism enzyme CYP3A in rat livers and its kinetic analysis. METHOD: Microsome enzyme was prepared by differential velocity centrifugation. Michaelis constant (Km) and maximum velocity (Vmax) of CYP3A, 50% inhibitory concentration of PNS on CYP3A, and the inhibition type and the inhibition constant of CYP3A (Ki, Kis) of PNS on CYP3A were calculated by Lineweaver-Burk and the low of semi-effect-probit. RESULT: Total saponins of the root and rhizome of panax notoginseng inhibited CYP3A activity, with IC50 of 689.54 mg x L(-1). Compared with the substrate aminopyrine, CYP3A showed Km of 0.036 mmol x L(-1) and Vmax of 21.01 micromol min(-1) x g(-1). Total saponins of the root and rhizome of panax notoginseng showed a mixed inhibition on CYP3A, with the inhibition constants of 247.79 mg x L(-1) (Ki) and 321.79 mg x L(-1) (Kis). CONCLUSION: Total saponins of the root and rhizome of panax notoginseng have a significant effect on CYP3A activity in rat livers.

A qualitative study of the first batch of medical assistance team's first-hand experience in supporting the nursing homes in Wuhan against COVID-19.

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) has global impact, Wuhan in Hubei province is a high-risk area. And the older people in nursing homes are the most susceptible group to COVID-19. The aim of this study was to describe the practice and experience of the first-line medical team, to provide insights of coping with COVID-19 in China. METHOD: This qualitative study used a descriptive phenomenological design to describe the experience of medical staff supported the nursing homes in Wuhan fighting against COVID-19. Unstructured interviews via online video were conducted with seven medical staffs who supported the nursing homes in Wuhan. Data were analyzed using content analysis in five main themes: for nursing homes, we interviewed the difficulties faced at the most difficult time, services for the older people, and prevention and management strategies, for the medical staff, the psychological experience were interviewed, and the implications for public health emergencies were also reported. CONCLUSIONS: It is imperative that effective preventive and response measures be implemented to face the outbreak of COVID-19 and meet the care needs of older people in the context of COVID-19. IMPLICATIONS: Findings will inform managers of some reasonable instructional strategies for implementing effective infection management. Nursing homes need to provide targeted services to help alleviating their bad psychology for residents.

Measurements of the parapapillary atrophy area and other fundus morphological features in high myopia with or without posterior staphyloma and myopic traction maculopathy.

AIM: To investigate the affecting factors of parapapillary gamma and delta zones and other fundus morphological features in high myopia. METHODS: Seventy high myopia patients were included in this retrospective observational study and 47 patients were female. Patients were divided into three groups: no posterior staphyloma (no PS), PS with myopic traction maculopathy (PS with MTM), and PS without MTM using 3-dimensional magnetic resonance imaging and optical coherence tomography. MTM patients were further classified into three types [epiretinal membrane, macular hole, and macular retinoschisis (MRS)]. Diameters of the gamma and delta zones were measured among other morphometric variables using fundus photographs. RESULTS: Of the 70 individuals (127 eyes), the mean age was 57.46±13.56y. In univariate analysis, morphological features changed most dramatically in PS with MTM patients, who had the largest gamma zone diameters, the largest disk-fovea distance (DFD) and disk-fovea angle, and the smallest angle kappa and vertical distance of temporal arterial arcade. However, their horizontal delta zone diameter was smaller than in the patients with PS yet without MTM. In multivariate analysis, with axial length (AL) and age adjusted, the horizontal diameter in the delta zone of the PS without MTM group was still significantly larger than in the PS with MTM group (P=0.024). Comparing the three subtypes of MTM patients, the diameters of the gamma zone and DFD in MRS group were the largest. CONCLUSION: The characteristics of the gamma and delta zones change inconsistently in different stages of high myopia. These changes may be associated with anatomical changes caused by local traction. Factors such as PS, AL and age play an important role. These findings may provide a hint about the pathogenesis of traction in high myopia.

Association of candidate gene polymorphisms with diabetic retinopathy in Chinese patients with type 2 diabetes.

AIM: To investigate the association between a set of six candidate genes and the risk of diabetic retinopathy (DR) in an urban community cohort of Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: A population-based cross-sectional study. The diabetic subjects were recruited from an urban community in Beijing and categorized into groups of proliferative diabetic retinopathy (PDR), non-proliferative diabetic retinopathy (NPDR), or diabetic without any retinopathy (DWR) based on the fundus photography and duration of diabetes. Six candidate genes, including advanced glycation end product specific receptor (AGER), aldose reductase (AKR1B1), inducible nitric oxide synthase (iNOS), pigment epithelium derived factor (PEDF), tumor necrosis factor-alpha (TNF-α), and paraoxonase 1 (PON1), were chosen based on Meta-analysis of genetic association studies for DR and biochemical pathways implicated in DR progression. The allele and genotype distribution of 21 functional single-nucleotide polymorphisms (SNPs) in those 6 candidate genes were investigated using MassARRAY genotyping system. RESULTS: Among 1461 diabetic patients recruited from community, 569 were selected in following genotyping analysis, including 97 patients with PDR, 217 with NPDR, and 255 with DWR. For the promoter variant rs1051993 in AGER gene, the distribution of allele and genotype in PDR group differed from that in DWR group (allele: P=0.011; genotype: P=0.01). Compared with DWR, patients with PDR had lower frequencies of heterozygous genotype GT (9.8% for DWR, 1% for PDR, OR: 0.10, 95%CI: 0.01-0.72) and minor allele T (4.9% for DWR, 0.5% for PDR, OR: 0.10, 95%CI: 0.01-0.75). In multivariate model, the distribution of genotype for rs1051993 in PDR group was significantly different from that in DWR group (GT vs GG: OR: 0.07, 95%CI: 0.01-0.61, P<0.001). No association with DR was observed in other genotyped SNPs. CONCLUSION: The data suggest a significant association of the promoter variant rs1051993 in AGER gene with PDR in Chinese cohort with T2DM.

Comparison of ocular parameters of two biometric measurement devices in highly myopic eyes.

AIM: To compare the differences and agreement of ocular biometric parameters in highly myopic eyes obtained by optical biometric measurement instruments, the OA-2000 and IOLMaster 500. METHODS: Totally, 90 patients (90 eyes) were included. They were divided into high myopia group and control group. Ocular parameters, including axial length (AL), mean keratometry (Km), anterior chamber depth (ACD), and white to white (WTW), were obtained from the OA-2000 and IOLMaster 500. RESULTS: For the control group, we applied Bland-Altman graphs to assess the 95% limits of agreement (LoA) for most parameters including AL, ACD, Km, and WTW (-0.24 to 0.29 mm, -0.22 to 0.45 mm, -0.39 to 0.31 D, and -0.90 to 0.86 mm, respectively). In high myopia patients, AL, ACD, Km values had wider 95% LoA (-0.34 to 0.32 mm, -0.36 to 0.34 mm, -0.57 to 0.47 D, respectively), except WTW (-0.80 to 0.68 mm). Differences were not statistically significant between these two instruments (P>0.05). CONCLUSION: Most parameters obtained by the OA-2000 and IOLMaster 500 are comparable, including the AL, ACD, and K values. Among them, the agreement of the high myopia patients is poor compared to the patients without high myopia.

Protective Effects of Leukemia Inhibitory Factor on Retinal Vasculature and Cells in Streptozotocin-induced Diabetic Mice.

BACKGROUND: Leukemia inhibitory factor (LIF) has been reported to possess various pharmacological effects, including displaying vascular and neuroprotective properties, during retinal disease. The aim of this study was to investigate the vascular and structural changes in the retina of diabetic mice and to explore whether LIF prevents experimental diabetes-induced retinal injury in the early stages. METHODS: Diabetes was induced in C57Bl/6J mice with streptozotocin (STZ) injections. Successful diabetic animal models were randomly separated into two groups: the diabetic group (n = 15) and the LIF-treated group (n = 15). Normal C57BL/6 mice served as the normal control group (n = 14). Recombinant human LIF was intravitreally injected 8 weeks after the diabetic model was successfully established. Retinas were collected and evaluated using histological and immunohistochemical techniques, and flat-mounted retinas and Western blotting were performed at 18 weeks after the induction of diabetes and 2 days after the intravitreal injection of LIF. The analysis of variance test were used. RESULTS: Histological analysis showed that there were fewer retinal ganglion cells (RGCs) and the inner nuclear layer (INL) became thinner in the diabetic model group (RGC 21.8 ± 4.0 and INL 120.2 ± 4.6 µm) compared with the normal control group (RGC 29.0 ± 6.7, t = -3.02, P = 0.007; INL 150.7 ± 10.6 µm, t = -8.88, P < 0.001, respectively). After LIF treatment, the number of RGCs (26.9 ± 5.3) was significantly increased (t = 3.39, P = 0.030) and the INL (134.5 ± 14.2 µm) was thicker compared to the diabetic group (t = 2.75, P = 0.013). In the anti-Brn-3a-labeled retinas, the number of RGCs in the LIF-treated group (3926.0 ± 143.9) was obviously increased compared to the diabetic group (3507.7 ± 286.1, t = 2.38, P = 0.030), while no significance was found between the LIF-treated group and the control group (4188.3 ± 114.7, t = -2.47, P = 0.069). Flat-mounted retinas demonstrated that a disorganized, dense distribution of the vessel was prominent in the diabetic model group. Vessel distribution in the LIF-treated mouse group was typical and the thickness was uniform. The levels of phosphosignal transducer and activator of transcription 3 activation were obviously higher in the LIF-injected retinas than those in the diabetic control group (t = 3.85, P = 0.019) and the normal control (t = -3.20, P = 0.019). CONCLUSION: The present study provides evidence that LIF treatment protects the integrity of the vasculature and prevents retinal injury in the early stages of diabetic retinopathy in STZ-induced diabetic models.

The Beijing Desheng Diabetic Eye Study: rationale, design, methodology and baseline data.

AIM: To present the rationale, design, methodology, and the baseline data of the Beijing Desheng Diabetic Eye Study (BDDES), and to determine the prevalence of diabetic retinopathy (DR) and possible risk factors in patients with type 2 diabetes mellitus (T2DM) in an urban community of Beijing, China. METHODS: Community-based prospective cohort study of persons diagnosed with T2DM aged 30y or older. The main variables of interest are the presence and progression of DR as determined by the standardized ETDRS grading of seven fields fundus photographs. The presence and severity of DR were analyzed for possible correlations to non-genetic and genetic dispositions. RESULTS: A total of 1438 participants with data available for analysis, the prevalence of any DR was 35.4%. The prevalence of mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and proliferative diabetic retinopathy was 27.7%, 2.6%, 0.5% and 4.5%, respectively. By multiple logistic regression analysis, risk factors for the presence of any DR included male (P=0.031), lower income level (P=0.011), lower education background (P=0.022), longer duration of diabetes (P=0.001), younger age at diabetic onset (P=0.001), higher systolic blood pressure (P=0.007), higher glycosylated hemoglobin A1c levels (P=0.001), high albuminuria (P=0.03), and use of insulin (P<0.001). For vision-threatening DR, four factors were significant: younger age at diabetic onset (P<0.001), higher systolic blood pressure (P=0.042), high albuminuria (P<0.001), and use of insulin (P<0.001). CONCLUSION: The BDDES is the first large-scale ongoing cohort study of a Chinese urban population of persons with type 2 diabetes. Using standardized grading system comparable to large cohort studies from western populations, our baseline data shows that the prevalence of DR and major risk factors in this Chinese ethnic population are comparable to that found in the western population studies.

The relationship between insulin resistance/ß-cell dysfunction and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus: the Desheng Diabetic Eye Study.

AIM: To investigate the relationship between insulin resistance (IR)/ß-cell dysfunction and diabetic retinopathy (DR) in Chinese patients with type 2 diabetes mellitus (T2DM), and to explore further whether there were differences in the relationship among diabetic patients with higher and lower body mass index (BMI). METHODS: Cross-sectional study. A total of 1466 subjects with T2DM were recruited in a local Desheng Community of urban Beijing from November 2009 to June 2012 for the cohort of Beijing Desheng Diabetic Eye Study. Standardized evaluation was carried out for each participant, including questionnaire, ocular and anthropometric examinations, and laboratory tests. Seven fields 30° color fundus photographs were used for DR grading according to the Early Treatment Diabetic Retinopathy Study protocols. Homeostatis Model Assessment (HOMA) method was employed for IR and ß-cell function assessment. RESULTS: After excluding those participants who were treated with insulin (n=352) or had missing data of fasting insulin (n=96), and further excluding those with poor quality of retinal photographs (n=10), a total of 1008 subjects were included for the final analysis, 406 (40.3%) were men and 602 (59.7%) were women, age ranging from 34 to 86 (64.87±8.28)y. Any DR (levels 14 and above) was present in 278 (27.6%) subjects. After adjusting for possible covariates, the presence of any DR did not correlate with HOMA IR [odds ratio (OR) 1.51, 95% confidence interval (CI) 0.87-2.61, P=0.14] or HOMA ß-cell (OR 0.71, 95%CI 0.40-1.26, P=0.25). After stratification by BMI, the presence of any DR was associated positively with HOMA IR (OR 2.46, 95%CI: 1.18-5.12, P=0.016), and negatively with HOMA ß-cell (OR 0.40, 95%CI: 0.19-0.87, P=0.021) in the group of patients with higher BMI (≥25 kg/m2). In the group of patients with lower BMI (<25 kg/m2), the presence of any DR was not associated with HOMA IR (OR 1.00, 95%CI: 0.43-2.33, P=1.00) or HOMA ß-cell (OR 1.41, 95%CI: 0.60-3.32, P=0.43). CONCLUSION: The data suggest that higher IR and lower ß-cell function are associated with the presence of DR in the subgroup of diabetic patients with higher BMI. However, this association is not statistically significant in diabetic patients with lower BMI.

Association of choroidal thickness with early stages of diabetic retinopathy in type 2 diabetes.

AIM: To assess the correlation between choroidal thickness (CT) and the early stages of diabetic retinopathy (DR) in type 2 diabetic patients. METHODS: We divided 83 diabetic patients (51-80 years of age; 50 females) into non diabetic retinopathy group (NDR) and mild/moderate nonproliferative diabetic retinopathy (NPDR) group, and compared them with 26 non-diabetic control subjects (51-78 years of age; 16 females). Subfoveal choroidal thickness (SFCT) and parafoveal choroidal thickness (PFCT) were measured using enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT). Ocular health status, disease duration, body mass index, and hemoglobin A1c (HbA1c) were recorded. RESULTS: The mean ages of the NDR, NPDR, and control groups were 68.0±6.9y, 67.8±6.4y, and 65.1±6.3y, respectively (P=0.17). Pearson correlation of the right and left eyes for the control subjects was 0.95 and for the NDR subjects was 0.93. SFCT for the right eyes of the controls was 252.77± 41.10 µm, which was significantly thicker than that of the right eyes in NDR group (221.51±46.56 µm) and the worse eyes of the NPDR group (207.18±61.87 µm; ANOVA, P<0.01). In the diabetic patients pooled together, age was the only variable significantly associated with SFCT (multiple linear regression analysis, P=0.01). CONCLUSION: CT decreased significantly in the NDR and mild/moderate NPDR eyes compared with the control eyes. Age is significantly associated with SFCT in the diabetic patients. Diabetic choroidopathy may be present before clinical retinopathy.