The intracellular monoamine oxidase-A inhibitory activity and the protective effect of small hairtail-related peptides in nerve cells (SH-SY5Y).

This study was to investigate the inhibitory activity of small hairtail-related peptides (VFEVFW, LPNSLYQQ, LPNSLYQK, and FADAME) on intracellular monoamine oxidase-A (MAO-A) and their protective effects in a cell model. Specifically, the inhibition activity in SH-SY5Y cells indicated that VFEVFW and LPNSLYQK reduced ∼50% of MAO-A activity in cells, at 0.5 m m. The survival experiment demonstrated that the toxic effect of dexamethasone (DEX) on cells can be significantly alleviated in the presence of peptides, and these peptides can restore (>20%) the mitochondrial membrane potential of SH-SY5Y cells reduced by DEX. Circular dichroism displayed that peptides affected the secondary structure of MAO-A in a concentration-dependent manner. Finally, the real-time quantitative polymerase chain reaction assay revealed that the MAO-A inhibitory activity of the peptides was associated with the upregulation of brain derived neurotrophic factor/cAMP (Cyclic adenosine monophosphate) response element binding protein)/B-cell lymphoma-2 mRNA levels.

Effectiveness and safety of four different beta-blockers in patients with chronic heart failure.

In this study, we evaluated the effectiveness and safety of bisoprolol, metoprolol, carvedilol, and nebivolol in the treatment of chronic heart failure. The results demonstrated that bisoprolol improved the prognosis of chronic heart failure in comparison with carvedilol, and carvedilol exerted similar effects as metoprolol succinate and nebivolol and better effect than metoprolol tartrate (evidence levels: bisoprolol > carvedilol = metoprolol succinate = nebivolol > metoprolol tartrate; " > " means "prior to").

Isolation and identification of dipeptidyl peptidase-IV inhibitory peptides from Sacha inchi meal.

BACKGROUND: Sacha inchi meal (SIM) is a by-product of oil processing. Our previous studies showed that SIM hydrolysates exhibited dipeptidyl peptidase-IV (DPP-IV) inhibition activity. The objective of the present work was to identify and characterize the bioactive peptides from protein hydrolysates of SIM; enzyme kinetics and peptide-enzyme interaction were also investigated. RESULTS: From SIM hydrolysates, ten peptides responsible for the activity were identified: GPSRGF (GF-6), FPILSPDPA (FA-9), APYRRGGKI (AI-9), WPYH (WH-4), DPATWLALPT (DT-10), NPEDEFRQQ (NQ-9), APESKPVGV (AV-9), LEWRDR (LR-6), APVYWVQ (AQ-7) and LLMWPY (LY-6). The IC50 values of five peptides (GF-6, WH-4, AQ-7, AV-9 and LY-6) with better inhibitory activity on DPP-IV were within the range of 23.43-128.40 µmol L-1 . AQ-7 had the best activity, with an IC50 value of 23.43 µmol L-1 . Enzyme kinetics indicated the presence of various inhibition types (mixed, non-competitive and competitive). Isothermal titration microcalorimetry showed that the main forces of the binding sites between peptide (GF-6 or AQ-7) and DPP-IV were hydrogen bond, hydrophobic interaction and van der Waals force. The key residues involved in peptide-enzyme interaction were determined by molecular docking. Furthermore, at a concentration of 800 µmol L-1 , GF-6 was found to significantly increase the glucose consumption in insulin-resistant HepG2 cells (P < 0.05) compared with the model group. CONCLUSION: Sacha inchi meal-derived peptides displayed potent DPP-IV inhibition activity and could be used in the health food industry and as lead compounds for diabetes therapy. © 2023 Society of Chemical Industry.

The Efficacy and Safety of Sacubitril/Valsartan in Heart Failure Patients: A Review.

Heart failure (HF) is one of the leading causes of morbidity and mortality worldwide. Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, has been approved for the treatment of HF. At present, there have been few systematic and detailed reviews discussing the efficacy and safety of sacubitril/valsartan in HF. In this review, we first introduced the pharmacological mechanisms of sacubitril/valsartan, including the reduction in the degradation of natriuretic peptides in the natriuretic peptide system and inhibition of the renin-angiotensin system. Then, we summarized the efficacy of sacubitril/valsartan in HF patients with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF) including the reduction in risks of mortality and hospitalization, reversal of cardiac remodeling, regulation of biomarkers of HF, improvement of the quality of life, antiarrhythmia, improving renal dysfunction and regulation of metabolism. Finally, we discussed the safety and tolerability of sacubitril/valsartan in the treatment of HFrEF or HFpEF. Compared with ACEIs/ARBs or placebo, sacubitril/valsartan showed good safety and tolerability, although the risk of hypotension might be high. In conclusion, the overwhelming majority of studies show that sacubitril/valsartan is effective and safe in the treatment of HFrEF patients but that it has little benefit in HFpEF patients. Sacubitril/valsartan will probably be a promising anti-HF drug in the near future.

Temporal changes and prognostic value of plasma ghrelin level in patients with acute heart failure: a prospective study.

BACKGROUND: Plasma ghrelin levels can be elevated in patients with acute heart failure (AHF). This study aimed to analyze the temporal changes and prognostic value of ghrelin levels in patients with AHF. METHODS: This prospective study included patients with AHF at the Cardiology Department, Weifang People's Hospital (May 2018-October 2019), and age- and sex-matched healthy controls. Plasma ghrelin levels were measured. Multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were used to evaluate whether ghrelin levels could predict major cardiac adverse events (MACEs) during a 1-year follow-up. RESULTS: Finally, 92 patients with AHF and 50 healthy controls were enrolled. Ghrelin levels were higher in patients with AHF at 1, 3, 12, and 24 h compared with controls (all P < 0.01). Ghrelin levels in the AHF group were higher at 3 and 12 h than at 1 and 24 h (P < 0.001). Ghrelin level at 3 h in patients with AHF was negatively correlated with the left ventricular end-diastolic diameter and left ventricular ejection fraction (both P < 0.05). MACEs occurred in 48 patients with AHF. Ghrelin levels were higher in the MACE group than in the non-MACE group at 1 (P = 0.011) and 3 h (P = 0.034). Multivariable regression showed that ghrelin level at 3 h was independently associated with MACEs [OR = 0.629, 95% confidence interval (CI): 0.515-0.742, P = 0.010], but the area under the ROC curve was only 0.629 (95% CI 0.515-0.742). CONCLUSIONS: Plasma ghrelin levels are elevated in AHF and patients with MACEs during follow-up.

OsIAA20, an Aux/IAA protein, mediates abiotic stress tolerance in rice through an ABA pathway.

In plants, auxin and ABA play significant roles in conferring tolerance to environmental abiotic stresses. Earlier studies have been shown that some Aux/IAA genes, with important signaling factors in the auxin pathway, were induced in response to drought and other abiotic stresses. However, the mechanistic links between Aux/IAA expression and general drought response remain largely unknown. In this study, OsIAA20, a rice Aux/IAA protein, shown with important roles in abiotic stress. Phenotypic analyses revealed that OsIAA20 RNAi transgenic rice reduced drought and salt tolerance; whereas, OsIAA20 overexpression plants displayed the opposite phenotype. Physiological analyses of OsIAA20 RNAi rice grown under drought or salt stress showed that proline and chlorophyll content significantly decreased, while malondialdehyde content and the ratio of Na+/ K+ significantly increased. In addition, OsIAA20down-regulation reduced stomatal closure and increased the rate of water loss, while transgenic plants overexpressing OsIAA20 exhibited the opposite physiological responses. Furthermore, an ABA-responsive gene, OsRab21, was down-regulated in OsIAA20 RNAi rice lines and upregulated in OsIAA20 overexpression plants. Those results means OsIAA20 played an important role in plant drought and salt stress responses, by an ABA dependent mechanism, and it will be a candidate target gene used to breed abiotic stress tolerance.

Risk factors for subretinal fibrosis after anti-VEGF treatment of myopic choroidal neovascularisation.

PURPOSE: To assess the incidence, clinical features and predictive risk factors of subretinal fibrosis after treatment of active myopic choroidal neovascularisation (mCNV) with anti-vascular endothelial growth factor (VEGF). METHODS: This post-hoc analysis of a randomised controlled trial included a total of 54 patients with active mCNV. The clinical data at baseline, month 3 and month 12 were used. Fundus photography and optical coherence tomography at month 3 were used to determine the presence of subretinal fibrosis after anti-VEGF therapy, and its incidence was calculated. Best-corrected visual acuity (BCVA), Visual Function Questionnaire-25 score, macular integrity index (MI) and their changes were compared between eyes with and without subretinal fibrosis. A logistic regression model was used to evaluate the risk factors of subretinal fibrosis. RESULTS: Subretinal fibrosis occurred in 22 of 54 eyes with mCNV. Patients with subretinal fibrosis achieved similar BCVA improvement in comparison with those without fibrosis at 3 and 12 months after the treatment; however, they had lower visual acuity, more subfoveal CNV (p=0.002), higher CNV thickness at baseline (p=0.016), larger CNV size (p=0.030), larger leakage area (p=0.021) and higher presence of advanced myopic maculopathy (p=0.035). Age <45 years, BCVA <60 ETDRS letters, and MI index <20 at baseline were the predictors for subretinal fibrosis occurrence in a logistic regression model. CONCLUSIONS: The incidence of subretinal fibrosis after anti-VEGF therapy was 40.7% in eyes with mCNV. Age, baseline BCVA and MI index could serve as predictive risk factors of subretinal fibrosis after anti-VEGF treatment in patients with mCNV.

EAF2 loss induces prostatic intraepithelial neoplasia from luminal epithelial cells in mice.

Defining the cell of origin for prostatic carcinogenesis is fundamentally important for understanding the mechanisms leading to prostate cancer. Lineage tracing studies have demonstrated that luminal epithelial cells are capable of self-replication in multiple organs, including the adult murine prostate, and cell of prostate cancer origin studies have shown that while both the luminal and basal murine prostate epithelial cells are capable of neoplastic transformation, luminal cells are more efficient as the origin of prostate cancer. ELL-associated factor 2 (EAF2) is an androgen responsive tumor suppressive protein expressed by prostate luminal epithelial cells that is frequently down-regulated in primary prostate tumors. EAF2 knockdown induces prostate cancer cell proliferation and invasion in vitro and mice with Eaf2 deficiency develop epithelial hyperplasia and murine prostatic intraepithelial neoplasia (mPIN) lesions. Here, we utilized an Eaf2 knockout, PSA-CreERT2 transgenic model crossed with a fluorescent reporter line to show that Eaf2 deficiency induces mPIN lesions derived from the luminal cell lineage. These results suggest that PIN lesions in the Eaf2 knockout mouse were derived from prostate luminal epithelial cells, further suggesting that the prostatic luminal epithelial cell is the major origin of prostate carcinogenesis.

MORPHOLOGICAL CHARACTERISTICS AND VISUAL ACUITY OF HIGHLY MYOPIC EYES WITH DIFFERENT SEVERITIES OF MYOPIC MACULOPATHY.

PURPOSE: To investigate the morphological feature, visual acuity, and prevalence of macular complications in highly myopic eyes with different categories of myopic maculopathy (MM) according to the META-PM classification system. METHODS: The clinical records of 1,132 consecutive patients (1,841 eyes) with high myopia (refractive error ≤ -6D and axial length ≥26.5 mm), who visited the High Myopia Clinic at the Zhongshan Ophthalmic Center from January 2014 to July 2017, were reviewed. Fundus photograph, optical coherence tomography, axial length, refractive error, and best-corrected visual acuity were measured in each patient. Myopic maculopathy was graded from fundus photographs according to the META-PM classification, including tessellated fundus (C1), diffuse chorioretinal atrophy (C2), patchy atrophy (C3), and macular atrophy (C4). Other macular complications, including foveoschisis, extrafoveal schisis, full-thickness macular hole, epiretinal membrane, lacquer cracks, Fuchs spot, choroidal neovascularization, macular hemorrhage, and dome-shaped macula, were also investigated. RESULTS: Among the 1,841 eyes, 58 (3.15%) had no MM (C0), 779 (42.31%) had tessellated fundus only (C1), 524 (28.46%) had diffuse chorioretinal atrophy (C2), 352 (19.12%) had patchy chorioretinal atrophy (C3), and 128 (6.95%) had macular atrophy (C4). Age increased and best-corrected visual acuity became worse with the severity of MM (P < 0.01). Axial length was significantly longer with the severity of MM from C0 to C3 (P < 0.01), and spherical equivalent was greater with the severity of MM from C0 to C3 (P < 0.01) but was not different between C3 and C4 (P > 0.05). Subfoveal and parafoveal choroidal thicknesses were significantly thinner from C0 to C3 (P < 0.01). However, no significant difference was found between C3 and C4 in parafoveal choroidal thickness (P > 0.05). The complications were different among C0 to C4 correlated with MM (P < 0.01). The complications of foveoschisis, choroidal neovascularization, hemorrhage, lacquer cracks, Fuchs spot, dome-shaped macula, and epiretinal membrane were different between C1 and C2 (P < 0.01), but none of the complications were different between C3 and C4 (P > 0.05) except Fuchs spot (P = 0.009). CONCLUSION: The morphological and functional characteristics in eyes with high myopia were positively correlated with the severity of C0 to C3 MM. However, no morphological difference was found between C3 and C4. The absence of the progressive relationship between C3 and C4 might be determined.

ASSESSING THE ACTIVITY OF MYOPIC CHOROIDAL NEOVASCULARIZATION: Comparison Between Optical Coherence Tomography Angiography and Dye Angiography.

PURPOSE: This study aims to suggest a novel strategy for assessing the activity of myopic choroidal neovascularization (mCNV) based on optical coherence tomography angiography (OCTA) and to compare it with traditional fundus fluorescein angiography as the gold standard. METHODS: Macular OCTA images were obtained using RTVue XR Avanti with AngioVue. Morphologic features of mCNV lesions were analyzed. Characteristics of OCTA in 41 eyes with active mCNV and 41 eyes with inactive mCNV were analyzed. Optical coherence tomography angiography parameters associated with mCNV activity and the clinical significance of their sensitivity and specificity were analyzed using fundus fluorescein angiography as the reference. RESULTS: Of the total 108 patients, 82 had OCTA images with good quality which were included in this study. Several anatomical features of the CNV lesions, including overall appearance, branching with tiny vessels, presence of anastomoses/loops, and choroidal dark halo, were considered the possible parameters associated with mCNV activity. The intra- and interobserver agreements were substantial. To evaluate the CNV activity, sensitivity of overall appearance, tiny vascular branching, and presence of anastomoses or loops were 65.9%, 82.9%, and 73.2%, respectively, whereas the specificity was 87.8%, 90.2%, and 92.7%, respectively. However, the choroidal dark halo showed low specificity (46.3%) and failed in terms of evaluating the activity of mCNV. A novel comprehensive procedure integrating branching as a major parameter and overall appearance and presence of anastomoses/loops as minor parameters was developed to evaluate mCNV activity with sensitivity of 95.1% and specificity of 85.4%. CONCLUSION: In mCNV, the acquisition rate of clear OCTA images was 75.9%. A novel comprehensive diagnostic procedure combining mCNV appearance, vascular branching, and anastomoses/loops by OCTA may be a valuable strategy to evaluate neovascular activity in mCNV.

Symmetry of folds in FEVR: A genotype-phenotype correlation study.

Familial exudative vitreoretinopathy (FEVR) is a hereditary retinal vascular disorder. Among the various clinical phenotypes of this disease, retinal folds are the primary and typical feature of FEVR. However, little is known about the clinical characteristics, genetic spectrum, or potential phenotype-genotype correlation of retinal folds. Herein, we describe and analyze the clinical and genetic characteristics of retinal folds in FEVR. Eighty-nine patients with unilateral or bilateral retinal folds were included in this study. Clinical examinations showed that the retinal folds were bilateral in 37 patients (41.6%). Various retinal abnormalities were noted in the fellow eyes in the remaining 52 patients with unilateral folds. Most of the folds were located temporally (98.4%, 124/126), and were complete (97.6%, 123/126). 67.5% (60/89) probands were genetic confirmed FEVR. 25 novel pathogenic mutations (7 in FZD4, 7 in LRP5, 1 in NDP, 4 in TSPAN12, and 6 in KIF11) were identified in 25 families. Overall, 87.5% (14/16) and 73.7%(14/19) patients with LRP5 and FZD4 mutations were with unilateral folds, respectively.Nevertheless, only 25% (2/8), 36.4%(4/11) and 16.7%(1/6) patients with NDP, TSPAN12, and KIF11 mutations were with unilateral folds. Moreover, 85.7%(12/14),100% (6/6) and 100%(8/8) of the patients with mutated TSPAN12, KIF11, and NDP genes presented with symmetry in disease staging, while 55% and 64.7% of patients with FZD4 and LRP5 mutation displayed symmetry in staging. In conclusion, the majority of retinal folds extended completely and radially in the temporal peripheral retina. Patients with causative mutations in NDP, TSPAN12, or KIF11 were more likely to have bilaterally symmetrical severe retinopathy. In contrast, patients with LRP5 and FZD4 mutations displayed a relatively milder but broader spectrum of phenotypes and a higher frequency of asymmetry.

Next-Generation Sequencing in the Familial Exudative Vitreoretinopathy-Associated Rhegmatogenous Retinal Detachment.

Purpose: The purpose of this study was to investigate the genetic mutation spectrum in Chinese patients with familial exudative vitreoretinopathy-associated rhegmatogenous retinal detachment (FEVR-RRD) and to analyze the preliminary genotype-phenotype association. Methods: In this consecutive, cross-sectional study, 54 patients with FEVR-RRD were studied. Comprehensive ophthalmic examinations and targeted next-generation sequencing were performed in all patients. The genotype-phenotype association was also analyzed. Results: Causative mutations were identified in 38.9% (21/54) of patients (14/54 in LRP5, 4/54 in FDZ4, and 3/54 in TSPAN12). The study identified 22 potentially pathogenic mutations in 21 unrelated FEVR probands, and 14 were novel (10/15 in LRP5, 1/4 in FZD4, and 3/3 in TSPAN12). Furthermore, to explore the genotype-phenotype association, late-phase angiographic posterior and peripheral leakage (LAPPEL) was identified in 100% (4/4) of patients with FZD4 mutations and 100% (3/3) of patients with TSPAN12 mutations but only in 42.9% (6/14) of patients with LRP5 mutations. Extraretinal neovascularization (ERNV) was found in 100% (4/4) of patients with FZD4 mutations and in 66.7% (2/3) of patients with TSPAN12 mutations, but only in 21.4% (3/14) of patients with LRP5 mutations. Conclusions: The positive rate for pathogenic mutations in the known FEVR-associated genes was 38.9% (21/54). Among the mutations, LRP5 mutation was the predominant, accounting for 66.7% (14/21) of genetic positive patients. Patients with FEVR-RRD due to LRP5 mutations have less retinal vascular leakage or neovasculization than do patients with FEVR-RRD due to TSPAN12/FZD4 mutations. Moreover, 14 novel variants were found, which provided a deeper understanding of this disease.

Novel ocular findings in oculodentodigital dysplasia (ODDD): a case report and literature review.

BACKGROUND: Oculodentodigitaldysplasia (ODDD; MIM no. 164200) is a rare hereditary disorder caused by mutations in the gene GJA1.Ocular disorders included microcornea, cornea opacity and glaucoma. However, few studies described fundus findings. MATERIALS AND METHODS: Ophthalmic examination included visual acuity measurement, intraocular pressure (IOP) measurements, slit-lamp biomicroscopy, B-scan ultrasonography, Ultrasound biomicroscopy (UBM), spectral-domain optical coherence tomography (SD-OCT), ERG and retcam fluorescein angiogram. In addition, blood samples were taken from this patient for mutation analyze of GJA1. RESULT: The ophthalmic features of this patient were microcornea, cornea opacity, glaucoma as expected. Interestingly, the patient had a normal axial length with refractive status of emmetropia, but extremely retinal dysplasia and severe choroid thinning was noted. Flash electroretinogram (ERG) was extinguished in both eyes. This study identified a novel mutation c.91A>T in the GJA1 gene associated with fundus abnormalities. Bioinformatics and structural modeling suggested the mutation to be pathogenic. CONCLUSION: Our research expanded not only the mutation spectrum, but also the clinical characteristics of ODDD. To the best of our knowledge, this is the first report on anatomical and functional chorioretinal changes in ODDD patients. These novel ocular features highlight the importance of fundus morphological and functional evaluation in ODDD. ABBREVIATIONS: ODDD: oculodentodigital dysplasia; OCT: optical coherence tomography; ERG: electroretinogram; TACT: teller acuity card test; UBM: ultrasound biomicroscopy; MW: molecular weights; AL: axial length; Cx43: connexin 43; RPE: retinal pigment epithelium; RGCs: retinal ganglion cells; FEVR: familial exudative vitreoretinopathy; ROP: retinopathy of prematurity.

Two different initial treatment regimens of ranibizumab in myopic choroidal neovascularization: 12-month results from a randomized controlled study.

IMPORTANCE: The optimal treatment regimen for myopic choroidal neovascularization (mCNV) is essential to understand but currently poorly studied. BACKGROUND: To date, there is still no consensus on the optimal dosage and frequency of anti-vascular endothelial growth factor injections in treating mCNV. DESIGN: A prospective, single-centre, single-blind, randomized controlled study. PARTICIPANTS: Adult patients with active mCNV. METHODS: Patients were randomized 1:1 to one or three doses initial ranibizumab treatments. Additional injections were administered pro re nata (prn) over 12 mo. MAIN OUTCOME MEASURES: Number and frequency of injections. RESULTS: Fifty patients participated in the study. Patients in both 1 + prn or 3 + prn groups experienced similar best-corrected visual acuity gain and anatomical improvement, including central retinal thickness (CRT), CNV thickness, area of CNV and area of leakage. Over 12 mo, patients in the 1 + prn group received fewer ranibizumab injections (2.04 ± 1.22) compared with the 3 + prn group (3.58 ± 0.72, P<0.0001), but no statistic difference of the injection received was observed in the prn period. During the follow-up, 15 of 26 eyes in the 1 + prn group and 10 of 24 eyes in the 3 + prn group received additional injections after initial dosing (P = 0.2575). Cox regression analysis showed that 1 + prn, female, age > 55 y and CRT > 300 µm are risk factors for retreatment. CONCLUSIONS AND RELEVANCE: The eyes with a single loading dose achieved parallel anatomical and functional visual improvement, while required less injections over 1 y. The risk factors for retreatment include 1 + prn, female, older age and thick retina thickness.

Optical Coherence Tomography Angiography in Familial Exudative Vitreoretinopathy: Clinical Features and Phenotype-Genotype Correlation.

Purpose: To evaluate the microstructure of the fovea in patients with familial exudative vitreoretinopathy (FEVR) compared to healthy controls using optical coherence tomography angiography (OCTA). Methods: In this consecutive, cross-sectional, observational case series, 41 eyes of 41 patients diagnosed as FEVR and 37 eyes in 37 control subjects were studied. OCTA was utilized to automatically measure the foveal avascular zone (FAZ) and the vessel density (VD). Inner retinal thicknesses (IRT) and central retinal thickness (CRT) were measured with the instrument caliper. Targeted next-generation sequencing was performed, and phenotype-genotype association was analyzed. Results: Small FAZ was found in 31.70% (13/41) FEVR eyes but not in controls. Greater CRT and lower superficial foveal VD were noted in FEVR patients. FAZ is negatively correlated with IRT. Persistence of the inner retinal layer (IRL) in fovea was present in 48.78% (20/41) FEVR eyes but not found in controls. Zero percent (0/10) of patients with the low-density lipoprotein receptor-related protein 5 (LRP5) mutation, 50% (1/2) with the frizzled-4 (FZD4) mutation, and 66.67% (3/4) with the tetraspanin-12 (TSPAN12) mutation had preserved foveal IRL and small FAZ. Conclusions: Our data indicate FEVR status is associated with a significantly smaller FAZ, decreased vascular density in both the superficial and deep layers of parafoveal area, a thicker fovea, and an abnormally preserved IRL in fovea. In addition, patients with the LRP5 mutation had a milder phenotype than those with the FDZ4 or TSPAN12 mutations. These novel findings could provide insight into the understanding of the pathogenesis of FEVR.

Observational study of clinical characteristics of dome-shaped macula in Chinese Han with high myopia at Zhongshan Ophthalmic Centre.

PURPOSE: To evaluate the prevalence of dome-shaped macula (DSM) in highly myopic eyes among Chinese Han and to detect the correlation with myopic maculopathy and macular complications. METHODS: A total of 736 Chinese Han patients (1384 eyes) with high myopia (refractive error≤6.0 diopters or axial length ≥26.5 mm) are reviewed based on information entered into a high-myopia database at Zhongshan Ophthalmic Centre. Subfoveal choroidal thickness (SFCT) and parafoveal choroidal thickness (PFCT) are measured. The prevalence of DSM in patients with myopic maculopathy is categorised from C0 to C4. Clinical features, including macular complications, SFCT and PFCT, are compared between myopic eyes with and without DSM. RESULTS: Among the 1384 eyes, 149 (10.77%) show DSM. In highly myopic eyes without macular complications, the best corrected visual acuity is significantly worse in patients with DSM (p=0.002), and the ratio between subfoveal and parafoveal choroidal thickness (S/PCT) is significantly elevated in patients with DSM (p=0.021). The proportion of foveal schisis (17.24% vs 62.86%) is much lower in eyes with DSM compared with those without DSM. However, the proportions of extrafoveal schisis (39.66% vs 5.37%), foveal serous retinal detachment (SRD) (5.17% vs 0) and epiretinal membrane (ERM) (24.14% vs 10.74%) are much higher in eyes with DSM. The proportion of DSM was lower in C0 and C1, but higher proportion of DSM was found in C3 and C4. CONCLUSIONS: DSM is found in 10.77% of highly myopic eyes among Chinese Han. DSM might be a protective mechanism for foveal schisis and a risk factor for extrafoveal schisis, SRD and ERM.

Mechanism of fibrosis inhibition in laser induced choroidal neovascularization by doxycycline.

To explore the mechanisms underlying doxycycline suppression of fibrosis in laser-induced choroidal neovascularization (LCNV), C57BL/6J male mice (aged from 6 to 8 weeks) received intraperitoneal injections of PBS/doxycycline solution from one day before laser injury until they were sacrificed. Leakage was assessed by FA, and CNV (stained by IB4) or fibrosis (stained by collagen type I) size was measured. The percentage of Pan-keratin+α-SMA+ cells was counted in the eyes' cryostat sections by immunohistochemistry. qPCR was used to measure the mRNA of markers of pan-macrophages, M1 and M2-type macrophages (M1 and M2), markers of EMT, and markers in the downstream of STAT6 signaling. Western blotting was used to analyze the expression of Arg-1, α-SMA, E-cadherin, pSTAT6 and STAT6. Our data showed that doxycycline inhibited leakage from CNV, areas of CNV on day 7 and day 14, and suppressed fibrosis, and the ratio of fibrotic/angiogenic areas during day 7 to day 35. We also showed attenuation of EMT in the doxycycline group. The percentage of Pan-keratin+α-SMA+ cells was lower in the doxycycline group than in the control group. The mRNA and protein levels of mesenchymal markers were downregulated in the doxycycline group, while the epithelial marker was upregulated. In addition, our data showed that the protein expression of Arg-1, the mRNA expression of M1 and M2-markers, were both inhibited by doxycycline, while the level of pan-macrophages (f4/80) showed no significant difference in two groups. Finally, our results showed that doxycycline was able to modulate the STAT6 signaling in transcript and protein levels. Accordingly, we suggested that the mechanism of doxycycline-mediated inhibition of fibrosis in CNV occurs through the STAT6 pathway.

Retinal pigmental epithelium elevation and external limiting membrane interruption in myopic choroidal neovascularization: correlation with activity.

PURPOSE: To describe the morphological changes in myopic choroidal neovascularization (mCNV) on spectrum domain optical coherence tomography (SD-OCT) and to find a new strategy to evaluate their activity. METHODS: Characteristics of SD-OCT and fundus fluorescein angiography (FFA) before and after ranibizumab treatment of 52 eyes with active mCNV were analyzed. SD-OCT parameters associated with mCNV activity and the clinical significance of their sensitivity and specificity were analyzed using FFA as a standard reference. Retinal pigment epithelium (RPE) elevation was noted as highly correlated to the mCNV activity. RESULTS: Intraobserver agreement was substantial for all OCT parameters. However, interobserver agreement was low for intraretinal fluid (IRF). To evaluate the CNV activity, sensitivity of presence of subretinal fluid (SRF) and interruption of ellipsoid zone (EZ) was 23.9 and 82.1%, and specificity was 97.5 and 19.8%. External limiting membrane (ELM) interruption showed high sensitivity (97.0%) but low specificity (55.6%) due to the development of RPE elevation. A novel two-step procedure using ELM interruption and RPE elevation was developed to evaluate mCNV activity with sensitivity 92.5% and specificity 95.1%, respectively. Final agreement was as high as 93.9%, with a kappa value of 0.877 (P < 0.001). CONCLUSIONS: A novel two-step diagnostic procedure combining ELM interruption with RPE elevation is considered a valuable guide for diagnosis and monitoring of mCNV.

Arbuscular mycorrhizal fungi and rhizobium facilitate nitrogen uptake and transfer in soybean/maize intercropping system.

The tripartite symbiosis between legumes, rhizobia and mycorrhizal fungi are generally considered to be beneficial for the nitrogen (N) uptake of legumes, but the facilitation of symbiosis in legume/non-legume intercropping systems is not clear. Therefore, the aims of the research are as follows: (1) to verify if the dual inoculation can facilitate the N uptake and N transfer in maize/soybean intercropping systems and (2) to calculate how much N will be transferred from soybean to maize. A pot experiment with different root separations [solid barrier, mesh (30 µm) barrier and no barrier] was conducted, and the (15)N isotopic tracing method was used to calculate how much N transferred from soybean to maize inoculated with arbuscular mycorrhizal fungi (AMF) and rhizobium in a soybean (Glycine max L.cv. Dongnong No. 42)/maize (Zea mays L.cv. Dongnong No. 48) intercropping system. Compared with the Glomus mosseae inoculation (G.m.), Rhizobium SH212 inoculation (SH212), no inoculation (NI), the dual inoculation (SH212+G.m.) increased the N uptake of soybean by 28.69, 39.58, and 93.07% in a solid barrier system. N uptake of maize inoculated with both G. mosseae and rhizobium was 1.20, 1.28, and 1.68 times more than that of G.m., SH212 and NI, respectively, in solid barrier treatments. In addition, the amount of N transferred from soybean to maize in a dual inoculation system with a mesh barrier was 7.25, 7.01, and 11.45 mg more than that of G.m., SH212 and NI and similarly, 6.40, 7.58, and 12.46 mg increased in no barrier treatments. Inoculating with both AMF and rhizobium in the soybean/maize intercropping system improved the N fixation efficiency of soybean and promoted N transfer from soybean to maize, resulting in the improvement of yield advantages of legume/non-legume intercropping.