Insulin-like growth factor binding protein related protein 1 knockdown attenuates hepatic ?brosis via the regulation of MMPs/TIMPs in mice

Background: Previous research suggested that insulin-like growth factor binding protein related protein 1(IGFBPrP1), as a novel mediator, contributes to hepatic fibrogenesis. Matrix metalloproteinases(MMP) and tissue inhibitors of metalloproteinases(TIMP) play an essential role in hepatic fibrogenesis by regulating homeostasis and remodeling of the extracellular matrix(ECM). However, the interaction between IGFBPrP1 and MMP/TIMP is not clear. The present study was to knockdown IGFBPrP1 to investigate the correlation between IGFBPrP1 and MMP/TIMP in hepatic fibrosis. Methods: Hepatic fibrosis was induced by thioacetamide(TAA) in mice. Knockdown of IGFBPrP1 expression by ultrasound-targeted microbubble destruction-mediated CMB-shRNA-IGFBPrP1 delivery, or inhibition of the Hedgehog(Hh) pathway by cyclopamine treatment, was performed in TAA-induced liver fibrosis mice. Hepatic fibrosis was determined by hematoxylin and eosin and Sirius red staining. Hepatic expression of IGFBPrP1, α-smooth muscle actin( α-SMA), transforming growth factor β 1(TGF β1), collagen I, MMPs/TIMPs, Sonic Hedgehog(Shh), and glioblastoma family transcription factors(Gli1) were investigated by immunohistochemical staining and Western blotting analysis. Results: We found that hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I were increased longitudinally in mice with TAA-induced hepatic fibrosis, concomitant with MMP2/TIMP2 and MMP9/TIMP1 imbalance and Hh pathway activation. Knockdown of IGFBPrP1 expression, or inhibition of the Hh pathway, reduced the hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I and re-established MMP2/TIMP2 and MMP9/TIMP1 balance. Conclusions: Our findings suggest that IGFBPrP1 knockdown attenuates liver fibrosis by re-establishing MMP2/TIMP2 and MMP9/TIMP1 balance, concomitant with the inhibition of hepatic stellate cell activation, down-regulation of TGF β1 expression, and degradation of the ECM. Furthermore, the Hh pathway mediates IGFBPrP1 knockdown-induced attenuation of hepatic fibrosis through the regulation of MMPs/TIMPs balance.

Interaction between insulin-like growth factor binding protein-related protein 1 and transforming growth factor beta 1 in primary hepatic stellate cells

BACKGROUND: We previously showed that insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) is a novel mediator in liver fibrosis. Transforming growth factor beta 1 (TGF beta 1) is known as the strongest effector of liver fibrosis. Therefore, we aimed to investigate the detailed interaction between IGFBPrP1 and TGF beta 1 in primary hepatic stellate cells (HSCs). METHODS: We overexpressed TGF beta 1 or IGFBPrP1 and inhibited TGF beta 1 expression in primary HSCs for 6, 12, 24, 48, 72, and 96 hours to investigate their interaction and observe the accompanying expressions of a-smooth muscle actin (alpha-SMA), collagen I, fibronectin, and phosphorylated-mothers against decapentaplegic homolog 2/3 (p-Smad2/3). RESULTS: We found that the adenovirus vector encoding the TGF beta 1 gene (AdTGF beta 1) induced IGFBPrP1 expression while that of alpha-SMA, collagen I, fibronectin, and TGF beta 1 increased gradually. Concomitantly, AdIGFBPrP1 upregulated TGF beta 1, alpha-SMA, collagen I, fibronectin, and p-Smad2/3 in a time-dependent manner while IGFBPrP1 expression was decreased at 96 hours. Inhibition of TGF beta 1 expression reduced the IGFBPrP1-stimulated expression of alpha-SMA, collagen I, fibronectin, and p-Smad2/3. CONCLUSIONS: These findings for the first time suggest the existence of a possible mutually regulation between IGFBPrP1 and TGF beta 1, which likely accelerates liver fibrosis progression. Furthermore, IGFBPrP1 likely participates in liver fibrosis in a TGF beta 1-depedent manner, and may act as an upstream regulatory factor of TGF beta 1 in the Smad pathway.

Increased serum levels of soluble CD146 and vascular endothelial growth factor receptor 2 in patients with exudative age-related macular degeneration

AIM: To investigate serum levels of soluble CD146(s CD146) and vascular endothelial growth factor receptor 2(VEGFR2) in patients with age-related macular degeneration(AMD). METHODS: Eighty-eight patients with exudative AMD and 45 sex-and age-matched healthy controls were enrolled in this study conducted in China. Serum samples was obtained from the patients with exudative AMD and from the controls. Serum sCD146 and VEGFR2 protein levels were measured using an enzyme-linked immunosorbent assay.RESULTS: We found that serum sCD146 and VEGFR2 protein levels were significantly higher in the patients with exudative AMD group than in the controls(t=3.859, P<0.001 and t=3.829, P<0.001, respectively). Serum sCD146 levels were significantly higher in patients with classic choroidal neovascularization(CNV) than in those with occult CNV(t=9.899, P<0.001). There was a significant difference in the trend for exudative AMD in the highest versus lowest quartile of circulating sCD146 levels(χ2=10.29, P=0.001). The receiver operating characteristic curve analysis showed that the area under the curve was 0.696 for s CD146(95%CI: 0.601-0.791) with an optimum diagnostic cut-off value of 157.16 ng/mL, a sensitivity of 55.7%, and a specificity of 82.2%.CONCLUSION: The serum sCD146 level increases and may be a biomarker for exudative AMD.

Serum vascular endothelial growth factor receptor-2 and adropin levels in age-related macular degeneration

AIM： To investigate the serum levels of vascular endothelial growth factor receptor-2（VEGFR-2） and adropin in age-related macular degeneration（AMD）patients.·METHODS： Ninety-eight AMD patients were included in the study. Seventy-eight age- and sex-matched healthy volunteers were recruited as the control group.Fundus florescein angiography and optical coherence tomography were performed to assess the posterior segment details. Serum VEGFR-2 and adropin levels were measured using enzyme-linked immunosorbent assays and compared between the study groups.· RESULTS： AMD group had significantly increased foveal retinal thickness, serum LDL and HDL levels and significantly decreased subfoveal choroidal thickness（P =0.01, 0.047, 0.025 and 〈0.001, respectively）. Serum VEGFR-2level revealed a significant decrease in AMD patients compared to controls（26.48 ±6.44 vs 30.42 ±7.92 ng/m L,P 〈0.001）. There was an insignificant increase in serum adropin level in AMD patients（6.17±3.19 vs 5.79±2.71 ng/m L,P =0.4）. Serum level of VEGFR-2 in AMD patients had a significant negative correlation with foveal retinal thickness（r =-0.226, P =0.025） and a significant positive correlation with subfoveal choroidal thickness（r=0.2, P=0.048）.·CONCLUSION： The current study demonstrated that the decreased serum VEGFR-2 level may be considered in the development of AMD. Adropin does not seem to play a role in the pathogenesis of AMD.

Vascular endothelial growth factor gene polymorphisms in age-related macular degeneration in a Turkish population

AIM:To assess the association between age-related macular degeneration(AMD) and three single nucleotide polymorphisms(SNPS) related to the vascular endothelial growth factor(VEGF) gene.METHODS:The patients who were diagnosed with AMD were included in this prospective study. Three SNPs(rs1413711, rs2146323, and rs3025033) of the VEGF gene were genotyped by real-time polymerase chain reaction in the genomic DNA isolated from peripheral blood samples of the 82 patients and 80 controls.RESULTS:The genotype frequencies of rs1413711 and rs2146323 were not significantly different between the study group and the control group(P =0.072 and P =0.058).However, there was a significant difference in the genotype frequencies of these SNPs between the wet type AMD and dry type AMD(P =0.005 and P =0.010,respectively). One of the SNPs(rs1413711) was also found to be associated with the severity of AMD(P =0.001)with significant genotype distribution between early,intermediate, and advanced stages of the disease. The ancestral alleles were protective for both SNPs while the polymorphic alleles increased the risk for dry AMD.CONCLUSION:VEGF SNPs rs1413711 and rs2146323 polymorphisms are significantly associated with AMD subtypes in our population.

Allele Frequency Distribution of the NCAPG c.1326T>G SNP Associated with Growth-Related Traits in Niigata Population of Japanese Black Beef Cattle

Growth performance as well as marbling is the main breeding objectives in Japanese Black cattle, the major beef breed in Japan. A previous study has identified the c.1326T>G single nucleotide polymorphism (SNP) in the NCAPG (non-SMC condensin I complex, subunit G) gene that leads to the amino acid change p.Ile442Met in the NCAPG protein, which is a candidate causative variation for a bovine carcass weight (CWT) quantitative trait locus (QTL). In this study, we first confirmed the association of the c.1326T>G SNP with the growth-related traits, CWT, rib eye area (REA) and rib thickness (RT), and showed significant effect of the SNP genotypes on the marbling trait, beef marbling score (BMS), in the Japanese Black beef cattle population of the Niigata prefecture, with the G allele being associated with a favorable phenotype of these traits. Thus, we concluded that the c.1326T>G SNP is useful for effective marker-assisted selection to increase meat quality and meat productivity in Japanese Black beef cattle of the Niigata prefecture. Furthermore the frequency of the favorable G allele of the c.1326T>G SNP in the Niigata prefecture population was significantly lower than the frequency of this allele in Japanese Black cattle population of the Kagoshima prefecture. However, no statistically significant difference was detected between the allele frequencies estimated by maternal alleles in the half-sib progeny steers in the Niigata prefecture population and obtained in Japanese Black cattle population of the Kagoshima prefecture.

A GENERAL CONSTITUTIVE RELATION FOR FATIGUE CRACK GROWTH ANALYSIS OF METAL STRUCTURES

Crack growth rate curves are the fundamental material property for metal structures under fatigue loading. Although there are many crack growth rate curves available in the literature, few of them showed the capability to explain various special phenomena observed in tests. A modified constitutive relation recently proposed by McEvily and his co-workers showed very promising capability. This modified constitutive relation is further generalized by (1) introducing an unstable fracture condition; (2) defining a virtual strength to replace the yield stress; and (3) defining an overload and underload parameter. The performances of this general constitutive relation for fatigue crack growth is extensively studied and it is found that this general constitutive relation is able to explain various phenomena observed with particular strong capability on load sequence effect.

Analytically Derived Wind Wave Growth Relations

By the use of the 3/2 power law presented by Toba combined with the significant wave energy balance equation for wind wave, wind wave growth at a limited fetch is analytically investigated. The new wind wave growth relations (WWGRs) are analytically derived with sheltering coefficient and wind drag coefficient as parameters. The geometrical average of observational values of sheltering coefficient and the arithmetic average of observational values of wind drag coefficient are applied to determine the new WWGRs. Comparisons with existing empirical WWGRs are made.

Relationships of growth and mortality to enzymatic activity,and the relative mRNA expression of cultured scallops Patinopecten yessoensis in the Yellow Sea, China

The bottom aquaculture of yesso scallop (Patinopecten yessoensis) has developed rapidly in the north of Yellow Sea, China, but not without accompanying productivity problems. We, therefore, conducted field surveys to investigate factors related to growth and mortality rates of bottom-cultured scallops after release. Specifically, we focused on the effects of total antioxidant capacity (TAOC) and three key enzymes involved in antioxidant and metabolic function:glutamic pyruvic transaminase (GPT), lactic dehydrogenase (LDH), and superoxide dismutase (SOD). Across summer and winter, we also measured the relative mRNA expression of GPT and SOD to understand their seasonal variation in the scallops, along with how such variation correlated to growth and mortality. Results show that bottom cultured scallops experienced mass mortality during the first six months post-release. During winter (December), scallops grew more rapidly and suffered less mortality than in summer (August). The observed lower performance probably resulted from less advantageous environmental factors during the summer seasons, such as high temperature and low dissolved oxygen. These environmental stressors enhance protein consumption while decreasing energetic resources in scallops. Furthermore, scallops in summer exhibited high antioxidant levels that probably competed for energy with process integral to growth and survival. These negative factors combined to elevate mortality rates. In conclusion, we provided evidence suggesting correlations between metabolic/antioxidant activity and growth and mortality of bottom-cultured yesso scallops. These correlations implied us an accurate method to estimate the performance of bottom culture system. Suggestions about innovative aquaculture techniques were also discussed in the study. Our results might provide a possible guideline to the improvement of bottom culture techniques for this commercially valuable seafood species.

Photosynthetic Light Utilization Efficiency, Water Relations and Leaf Growth of C3 and CAM Tropical Orchids under Natural Conditions

Native orchid species of Singapore in their natural conditions experience stress from high irradiance, high temperatures and periods of extended low rainfall, which impact orchid plant physiology and lead to reduced growth and productivity. In this study, it was found that there was a reduction in photochemical efficiency of photosystem II (PSII) in 6 native orchid species under high light (HL) and Bulbophyllum membranaceum under low light (LL). There was chronic photoinhibition in these 6 orchid species over a period of 3 months after transplanting onto the tree trunks without watering and fertilization, especially in Coelogynes mayeriana and Bulbophyllum membranaceum under both HL and LL. This chronic photoinhibition caused by sustained period of water deficit in their natural conditions was later reversed by natural re-watering conditions from higher rainfall. These results indicate that water deficit has a greater impact on photosynthetic light utilization efficiency than excess light. The present study also showed that after natural rewatering, relative water content (RWC) of leaves and pseudobulbs generally increased. During the natural re-watering, total leaf area also gradually increased and reached maximum expansion after 7 weeks under both HL and LL, with some exceptions due to leaf abscission or decline in total leaf area, possibly a strategy for water conservation.

Influence of relative positions between RF coil and crucible on sapphire crystals by edge-defined film-fed growth(EFG) technique

To obtain the stable temperature field required for growing sapphire crystals, the influence of relative positions between RF coil and crucible on the performances of sapphires produced by edge-defined film-fed growth（EFG） technique was investigated. For comparison, the crucible was located at the top（case A） and the middle（case B） of the RF coil, respectively. Furthermore, the lattice integrities were studied by the double-crystal X-ray diffraction, and the dislocations were observed under the optical microscope and atomic force microscope after corroding in molten KOH at 390 ℃. The crystals in case B exhibit better lattice integrity with smaller full width at half maximum of 29.13 rad·s, while the value in case A is 45.17 rad·s. The morphologies of dislocation etch pits in both cases show typical triangular symmetry with smooth surfaces. However, the dislocation density of 2.8×104 cm-2 in case B is only half of that in case A, and the distribution is more uniform, compared to the U-shaper in case A.

Empirical Analysis on the Relations between Rural Residents' Consumption and Economic Growth——A Case of Liaoning Province

Liaoning is a granary province with a large agricultural population and great market potential. Expanding rural residents' consumption becomes a necessity for enlarging domestic demand, solving three agriculture problems and promoting sustainable and rapid economic development. The research shows that since invigorating old industrial base in Liaoning, the contribution rate of rural residents' consumption to economic motivation is low and unstable, which has become one of the choke points for the development of economy. By using the grey correlation method, the influences of rural residents' consumption in different periods to GDP per capita are analyzed, the results show that the consumption level of rural residents were increasing, but their contribution rate on economic growth showed the descending tend. The residential expenses stay in the major position of consumption expenses; the education and entertainment products and service consumption play an important role; the growth of transportation and telecommunication is slow; the expenses on medical care are low and its contribution rate on economic growth is relatively weak. The countermeasures on developing rural economy, increasing rural residents' income, improving rural consumption environment, accelerating rural infrastructure construction, constructing and perfecting rural social security system and expanding rural consumption credit market are put forward to expand rural residents' consumption demand and realize the sustainable development of economy.

Species divergence in seedling leaf traits and tree growth response to nitrogen and phosphorus additions in an evergreen broadleaved forest of subtropical China

Tree competitiveness generally depends on trait plasticity in response to environmental change.The effects of nitrogen(N)and phosphorus(P)on leaf trait variability by species is poorly understood,especially in China’s subtropical forests.This study examined the seedling leaf traits and net primary productivity of all trees>5 cm DBH of two dominant species,Schima superba and Castanopsis carlesii,in an evergreen broadleaved forest fertilized with nitrogen(+N),phosphorus(+P),and nitrogen plus phosphorus(N+P).The effect of N on seedling leaf traits was stronger than P,while fertilization in general was species dependent.Leaf mass per unit area decreased with N for S.superba seedlings but not for C.carlesii.Leaf N,P,and N/P ratios changed with N addition for both species.All four N fractions of carboxylation,bioenergetics,cell wall,and other N metabolites in C.carlesii leaves responded significantly to fertilization,while only the cell wall in S.superb a leaves responded.Other leaf functional traits,including light-saturated photosynthetic rates,water,N,and P use efficiencies,chlorophyll and non structural carbohydrate contents increased with N addition in S.superb a and by P addition in C.carlesii.Canopy closure at the stand-level increased due to N.Litter biomass and relative growth rate of S.superb a was not affected by any treatments,while both for C.carlesii significantly decreased with N+P addition.Collectively,nutrient limitation may vary at a small scale among species in a subtropical forest based on their responses of seedling traits and net primary productivity to fertilization.Seedling traits are not correlated with the net primary productivity of larger trees except for N fractions,because low light conditions induced by fertilization reduces the proportion of N allocated to photosynthesis in seedlings.In addition,acclimation differences of tree species may increase the uncertainty of community succession.

Temporal pattern of resolution/recurrence of choroidal neovascularization during bevacizumab therapy for wet age-related macular degeneration

AIMTo characterize temporal pattern of resolution and recurrence of naive choroidal neovascularization (CNV) secondary to wet age-related macular degeneration (AMD) treated with intravitreal bevacizumab on as needed regimen, and to analyze baseline risk factors for CNV resolution or recurrence.

Wave growth rate in a cylindrical metal waveguide with ion-channel guiding of a relativistic electron beam

This paper addresses the formulae and numerical issues related to the possibility that fast wave may be grown when a relativistic electron beam through an ion channel in a cylindrical metal waveguide. To derive the dispersion equations of the beam-wave interaction, it solves relativistic Lorentz equation and Maxwell＇s equations for appropriate boundary conditions. It has been found in this waveguide structure that the TM0m modes are the rational operating modes of coupling between the electromagnetic modes and the betatron modes. The interaction of the dispersion curves of the electromagnetic TM0m modes and the upper betatron modes is studied. The growth rates of the wave are obtained, and the effects of the beam radius, the beam energy, the plasma frequency, and the beam plasma frequency on the wave growth rate are numerically calculated and discussed.

Effect of relative humidity at chronic temperature on growth performance, glucose consumption, and mitochondrial ATP production of broilers

An experiment was conducted to investigate the effect of relative humidity(RH)at chronic temperature on growth performance,glucose consumption,and mitochondrial adenosine triphosphate(ATP)production of broilers.A total of 180 28-day-old Arbor Acres broilers(half males and half females)were randomly allocated to three treatments,each containing six replicates of 10 birds per treatment,using a completely randomized design.Birds were reared at 35,60 or 85%RH at 32℃for 15 days(temperature increased by 3℃every 3 days from 20 to 32℃within 15 days:20–23–26–29–32℃).RH affected(P<0.05)average daily feed intake(ADFI),average daily gain(ADG),average daily water consumption(ADWC),blood glucose concentrations,muscle glycogen levels,avian uncoupling protein(av UCP)mRNA expression,and cytochrome c oxidase(CCO)activity in liver of broilers at 42 days of age.The 85%RH decreased(P<0.05)ADFI,ADG and ADWC;35%RH decreased(P<0.02)ADG.Both 85 and 35%RH increased(P<0.01)blood glucose and decreased(P<0.05)muscle glycogen.Both 85 and 35%RH increased(P<0.05)av UCP mRNA expression.35%RH decreased(P<0.05)CCO activity.In conclusion,both high and low RH inceased glucose consumption and reduced mitochondrial ATP poduction,leading to a decline in growth rate.

Spontaneous or secondary to intravitreal injections of anti-angiogenic agents retinal pigment epithelial tears in age-related macular degeneration

·AIM:Toevaluatethevisualfunctionevolutionofretinal pigment epithelial(RPE) tears in patients with age-related macular degeneration(AMD) according to type of occurrence [spontaneous or secondary to anti-vascular endothelial growth factor(anti-VEGF) injection] and the topographic location of the tear after a two-year followup period.·METHODS: A total of 15 eyes of 14 patients with RPE tears in exudative AMD were analyzed retrospectively at the University Eye Clinic of Trieste. Inclusion criteria were: patient age of 50 or older with AMD and RPE tears both spontaneous occurring or post anti-VEGF treatment. Screening included: careful medical history,complete ophthalmological examination, fluorescein angiography(FA), indocyanine green angiography(ICG),autofluorescence and infrared imaging and optical coherence tomography(OCT). Patients were evaluated every month for visual acuity(VA), fundus examination and OCT. Other data reported were: presence of PED,number of injections before the tear, location of the lesion.·RESULTS:Meanfollow-up was24wk(SD±4wk). Atotal of 15 eyes were studied for RPE tear. In 6 cases(40%),the RPE tears occurred within two years of anti-VEGF injections the others occurred spontaneously. In 13cases(86.6%), the RPE tear was associated with pigment epithelial detachment(PED). In 7 cases(46.6%), the RPE tear occurred in the central area of the retina and involved the fovea. Two lesions were found in the parafoveal region, six in the extra-macular area. In all cases visual acuity decreased at the end of the follow-up period(P <0.01) independently of the type or the topographical location of the lesion.·CONCLUSION: RPE tear occurs in exudative AMD as a spontaneous complication or in relation to anti-VEGF injections. Visual acuity decreased significantly and gradually in the follow-up period in all cases. No correlation was found between visual loss and the type of onset or the topographic location of the tears.

Association of IGF1R polymorphisms(rs1546713) with susceptibility to age-related cataract in a Han Chinese population

AIM:To explore the susceptible association between the insulin-like growth factor-1 receptor(IGF1 R)single nucleotide polymorphism(SNP)and age-related cataract(ARC),and investigate the underlying mechanisms in human lens epithelium(HLE)cells.METHODS:Totally 1190 unrelated participants,comprising 690 ARC patients and 500 healthy individuals in Han Chinese population were recruited and genotyped for target SNP.Theχ2-test was used to detect genotypic distribution between the patient and control groups and the logistic regression was performed to adjust the age and gender.Meanwhile,different biological experimental methods,such as cell counting kit 8(CCK-8)assay,flow cytometry,quantitative real time polymerase chain reaction(Q-PCR)and Western blot,were used to detect cell viability,cell cycle progression and apoptosis in HLE cells or IGF1 R knockdown HLE cells.RESULTS:The rs1546713 in IGF1 R gene was identified(P=0.046,OR:1.606,95%CI:1.245-2.071),which shown a significant relevance with ARC risk under the dominant model.The results demonstrated that IGF1 R knockdown inhibited cell proliferation by inducing cell cycle arrested at S phase and promoting apoptosis.Mechanistically,the cell cycle blocked at S phase was linked with the alterations of cyclin A,cyclin B,cyclin E and P21.The pro-apoptosis function of IGF1 R may related with stimulating the activation of Caspase-3 and altering the expression levels of apoptotic proteins,including Bcl-2,Bax and Caspase-3.CONCLUSION:This study first report that IGF1 R polymorphisms may affect susceptibility to ARCs in Han Chinese population and provide new clues to understand the pathogenic mechanism of ARCs.Notably,IGF1 R is likely a potential target for ARC prevention and treatment.

Fixed bimonthly aflibercept in nave and switched neovascular age-related macular degeneration patients:one year outcomes

AIM: To determine real life clinical outcomes in poorly responsive and treatment-nave neovascular age-related macular degeneration(nv AMD) patients using bimonthly fixed dosing aflibercept regimen.METHODS: This was a retrospective study of 165 eyes with nv AMD started on aflibercept at Southampton Eye Unit between June 2013 and June 2014. Patients were either switched from pro re nata(PRN) ranibizumab/bevacizumab due to poor response(107 eyes), or treatment- nave( 58 eyes). Patients initially received 3-monthly intravitreal aflibercept injections followed by 2-monthly fixed doses. Clinic visits were scheduled at month 0, 4, 10 and 12. Mean change in best-corrected visual acuity(BCVA) and central retinal thickness(CRT)from baseline were assessed using the Wilcoxon signedrank test. The proportion of patients maintaining BCVA(<15 letters loss) at 12 mo was also evaluated.RESULTS: Mean BCVA change at month 12 was +3.29 and +4.67 letters in the switched and nave aflibercept groups respectively(P <0.01). BCVA was maintained in 95.3% of switched and 96.6% of nave patients. CRT at month 12 showed a decrease of -6.16 μm in the switched group and -35.36 μm in the nave group(P <0.01).Patients previously treated with ranibizumab/bevacizumab had on average received 7.4 ranibizumab/bevacizumab injections over 12.6 mo, attending 10 clinic visits. The fixed dosing aflibercept regimen required an average of 7.1 injections(nave group), 7.5 injections(switched group) and 4 clinic visits per year.CONCLUSION: Fixed bimonthly aflibercept is effective in both treatment-nave and poorly responsive nv AMD patients. Adopting a fixed dosing regimen can reduce patient burden without compromising on outcomes.

Factors Affecting the Relation of Fracture Toughness V_(GC) with Critical Void Growth Ratio R_C/R_O

The relationship between fracture toughness VGC and critical void growth RC/RO was studied for ten kinds of Steel. The macroscopic fracture toughness VGC was determined by using notched tensile specimens. and the microscopic parameters of critical void growth ratio RC/RO were quantitatively measured under SEM. Then, the coefhcient C in the relation VGC = C In(RC/RO) proposed in author's past work was specifically explored. The correlation of C with tensile proderty parameter φ=σyδ/(Eφn) was presented for the Steel investigated, and the effects of low temperature on C were also discussed. Results show that the coefficient C is linearly related to the parameter and insensitive to low temperature.