A feasibility study for objective evaluation of visual acuity based on pattern-reversal visual evoked potentials and other related visual parameters with machine learning algorithm.

BACKGROUND: To develop machine learning models for objectively evaluating visual acuity (VA) based on pattern-reversal visual evoked potentials (PRVEPs) and other related visual parameters. METHODS: Twenty-four volunteers were recruited and forty-eight eyes were divided into four groups of 1.0, 0.8, 0.6, and 0.4 (decimal vision). The relationship between VA, peak time, or amplitude of P100 recorded at 5.7°, 2.6°, 1°, 34', 15', and 7' check sizes were analyzed using repeated-measures analysis of variance. Correlations between VA and P100, contrast sensitivity (CS), refractive error, wavefront aberrations, and visual field were analyzed by rank correlation. Based on meaningful P100 peak time, P100 amplitude, and other related visual parameters, four machine learning algorithms and an ensemble classification algorithm were used to construct objective assessment models for VA. Receiver operating characteristic (ROC) curves were used to compare the efficacy of different models by repeated sampling comparisons and ten-fold cross-validation. RESULTS: The main effects of P100 peak time and amplitude between different VA and check sizes were statistically significant (all P < 0.05). Except amplitude at 2.6° and 5.7°, VA was negatively correlated with peak time and positively correlated with amplitude. The peak time initially shortened with increasing check size and gradually lengthened after the minimum value was reached at 1°. At the 1° check size, there were statistically significant differences when comparing the peak times between the vision groups with each other (all P < 0.05), and the amplitudes of the vision reduction groups were significantly lower than that of the 1.0 vision group (all P < 0.01). The correlations between peak time, amplitude, and visual acuity were all highest at 1° (rs = - 0.740, 0.438). VA positively correlated with CS and spherical equivalent (all P < 0.001). There was a negative correlation between VA and coma aberrations (P < 0.05). For different binarization classifications of VA, the classifier models with the best assessment efficacy all had the mean area under the ROC curves (AUC) above 0.95 for 500 replicate samples and above 0.84 for ten-fold cross-validation. CONCLUSIONS: Machine learning models established by meaning visual parameters related to visual acuity can assist in the objective evaluation of VA.

Chinese Guideline on the Management of Polypoidal Choroidal Vasculopathy (2022).

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

Rhodohalobacter sulfatireducens sp. nov., isolated from a marine solar saltern.

A novel Gram-stain-negative, oxidase-positive, catalase-positive, non-motile, facultatively anaerobic, rod-shaped bacterium, designated WB101T, was isolated from a marine solar saltern located in Wendeng, PR China. Strain WB101T shared a high level of 16S rRNA gene sequence similarity with Rhodohalobacter barkolensis 15182T (93.5%), R. halophilus JZ3C29T (93.2%), and 'R. mucosus' 8A47T (92.1%). Strain WB101T formed a species-level branch within the genus Rhodohalobacter in both phylogenetic and phylogenomic topologies. The DNA G + C content was 42.0%. Strain WB101T was found to have menaquinone-7 as the only respiratory quinone. The dominant cellular fatty acid (≥ 10%) was iso-C15:0. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylcholine. Characterisation based on phylogenetic, physiological, and biochemical properties indicated that strain WB101T represents a novel species of the genus Rhodohalobacter, and the name Rhodohalobacter sulfatireducens sp. nov. is proposed. The type strain is WB101T (= KCTC 92204T = MCCC 1H00518T).

Generation of sub-MHz and spectrally-bright biphotons from hot atomic vapors with a phase mismatch-free scheme.

We utilized the all-copropagating scheme, which maintains the phase-match condition, in the spontaneous four-wave mixing (SFWM) process to generate biphotons from a hot atomic vapor. The linewidth and spectral brightness of our biphotons surpass those of the biphotons produced with the hot-atom SFWM in the previous works. Moreover, the generation rate of the sub-MHz biphoton source in this work can also compete with those of the sub-MHz biphoton sources of the cold-atom SFWM or cavity-assisted spontaneous parametric down conversion. Here, the biphoton linewidth is tunable for an order of magnitude. As we tuned the linewidth to 610 kHz, the generation rate per linewidth is 1,500 pairs/(s·MHz) and the maximum two-photon correlation function, gs,as(2), of the biphotons is 42. This gs,as(2) violates the Cauchy-Schwarz inequality for classical light by 440 folds, and demonstrates that the biphotons have a high purity. By increasing the pump power by 16 folds, we further enhanced the generation rate per linewidth to 2.3×104 pairs/(s·MHz), while the maximum gs,as(2) became 6.7. In addition, we are able to tune the linewidth down to 290±20 kHz. This is the narrowest linewidth to date among all single-mode biphoton sources of room-temperature and hot media.

Integrin α5ß1 promotes BMCs mobilization and differentiation to exacerbate choroidal neovascularization.

Choroidal neovascularization (CNV) is an acknowledged pathogenic mechanism of various ocular diseases, and in situ cells and mobilized bone marrow-derived cells (BMCs) are thought to participate in this process. We aimed to evaluate the roles of integrin α5 in BMCs and vascular endothelial cells (VECs) in the CNV process mediated by SDF-1/CXCR4 signaling. Adult wild-type mice were engrafted with whole BMCs obtained from GFP transgenic mice and then laser injured to induce CNV. BMCs and RF/6A cells were cultured to discover the mechanism of CNV in vitro. BMCs were mobilized to CNV areas, which expressed elevated SDF-1 and CXCR4. When SDF-1 was intravitreally injected, the number of BMCs was profoundly increased. In the SDF-1-treated group, the levels of integrin α5 expressed on BMCs and VECs were significantly higher than those on the cells in the control group. SDF-1 significantly increased the expression and positive ratio of integrin α5, which was involved in the recruitment and differentiation of BMCs into BMC-derived VECs, and these effects were suppressed by the CXCR4 inhibitor AMD3100. The PI3K/AKT pathway rather than the ERK pathway mediated SDF-1/CXCR4 induction of integrin α5. Integrin α5 suppression efficiently prevented the production of TGF-ß and bFGF but not VEGF. Inhibiting the SDF-1/CXCR4-PI3K/AKT-integrin α5 axis reduced CNV severity. Integrin α5 participates in BMC recruitment and differentiation in SDF-1/CXCR4-induced CNV and inhibition of this pathway may be a new approach to inhibit CNV.

Metabolites Involved in Aerobic Degradation of the A and B Rings of Estrogen.

Various bacteria, mainly actinobacteria and proteobacteria, are capable of aerobic estrogen degradation. In a previous study, we used the obligate aerobic alphaproteobacterium Sphingomonas sp. strain KC8 as a model microorganism to identify the initial metabolites involved in the oxygenolytic cleavage of the estrogen A ring: 4-hydroxyestrone, a meta-cleavage product, and a dead-end product pyridinestrone acid. In this study, we identified the downstream metabolites of this aerobic degradation pathway using ultraperformance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). 4-Norestrogen-5(10)-en-3-oyl-coenzyme A and its closely related deconjugated (non-coenzyme A [non-CoA]) structure, 4-norestrogenic acid, were detected in the estrone-grown strain KC8 cultures. The structure of 4-norestrogenic acid was elucidated using nuclear magnetic resonance (NMR) spectroscopy. The extracellular distribution and the accumulation of 4-norestrogenic acid in the bacterial cultures indicate that the estrogen-degrading bacteria cannot degrade this deconjugated product. We also observed temporal accumulation and subsequent consumption of a common steroid metabolite, 3aα-H-4α(3'-propanoate)-7aß-methylhexahydro-1,5-indanedione (HIP), in the bacterial cultures. The metabolite profile and genomic analyses shed light on the biochemical mechanisms involved in the degradation of the A and B rings of natural estrogens. In this proposed aerobic pathway, C-4 of the meta-cleavage product is removed by a 2-oxoacid oxidoreductase through oxidative decarboxylation to produce the 4-norestrogen-5(10)-en-3-oyl-CoA. Subsequently, the B ring is cleaved by hydrolysis. The resulting A/B-ring-cleaved product is transformed into a common steroid metabolite HIP through ß-oxidation reactions. Accordingly, the A and B rings of different steroids are degraded through at least three peripheral pathways, which converge at HIP, and HIP is then degraded through a common central pathway.IMPORTANCE Estrogens, often detected in surface waters worldwide, have been classified as endocrine disrupting chemicals and carcinogens. Bacterial degradation is crucial for removing natural estrogens from natural and engineered ecosystems; however, current knowledge regarding the biochemical mechanisms and catabolic enzymes involved in estrogen biodegradation is very limited. Our estrogen metabolite profile and genomic analyses on estrone-degrading bacteria enabled us to characterize the aerobic estrogen degradation pathway. The results greatly expand our understanding of microbial steroid degradation. In addition, the characteristic metabolites, dead-end products, and degradation genes can be used as biomarkers to investigate the fate and biodegradation potential of estrogens in the environment.

SNAI1, an endothelial-mesenchymal transition transcription factor, promotes the early phase of ocular neovascularization.

Ocular neovascularization is a comprehensive process involved in retinal vascular development and several blinding diseases such as age-related macular degeneration and retinopathy of prematurity, with vascular endothelial growth factor (VEGF) regarded as the master regulator. However, the qualified effect of anti-VEGF therapy reveals that the underlying mechanisms are still not clearly identified. To initialize angiogenesis, endothelial cells undergo a phenotype switching to generate highly migratory and invasive cells. This process shares certain similar characters observed in endothelial-mesenchymal transition (EndMT). Here, we found that SNAI1, an EndMT transcription factor, was expressed by endothelial cells in both physiological and pathological ocular neovascularization. SNAI1 overexpression triggered cell morphological change and enhanced cell motility, while loss of SNAI1 attenuated migration, invasion and sprouting. RNA sequence analysis further revealed that SNAI1 knockdown decreased the expression of genes related to cytoskeleton rearrangement and ECM remodeling. Moreover, intravitreal injection of small interfering RNA of SNAI1 suppressed new vessel formation in developing retina as well as mice model of choroidal neovascularization and oxygen-induced retinopathy. Therefore, we propose that the EndMT transcription factor SNAI1 promotes the early phase of ocular neovascularization and may provide a potential therapeutic target.

Estrogen Degraders and Estrogen Degradation Pathway Identified in an Activated Sludge.

The environmental release and fate of estrogens are becoming an increasing public concern. Bacterial degradation has been considered the main process for eliminating estrogens from wastewater treatment plants. Various bacterial isolates are reportedly capable of aerobic estrogen degradation, and several estrogen degradation pathways have been proposed in proteobacteria and actinobacteria. However, the ecophysiological relevance of estrogen-degrading bacteria in the environment is unclear. In this study, we investigated the estrogen degradation pathway and corresponding degraders in activated sludge collected from the Dihua Sewage Treatment Plant, Taipei, Taiwan. Cultivation-dependent and cultivation-independent methods were used to assess estrogen biodegradation in the collected activated sludge. Estrogen metabolite profile analysis revealed the production of pyridinestrone acid and two A/B-ring cleavage products in activated sludge incubated with estrone (1 mM), which are characteristic of the 4,5-seco pathway. PCR-based functional assays detected sequences closely related to alphaproteobacterial oecC, a key gene of the 4,5-seco pathway. Metagenomic analysis suggested that Novosphingobium spp. are major estrogen degraders in estrone-amended activated sludge. Novosphingobium sp. strain SLCC, an estrone-degrading alphaproteobacterium, was isolated from the examined activated sludge. The general physiology and metabolism of this strain were characterized. Pyridinestrone acid and the A/B-ring cleavage products were detected in estrone-grown strain SLCC cultures. The production of pyridinestrone acid was also observed during the aerobic incubation of strain SLCC with 3.7 nM (1 µg/liter) estrone. This concentration is close to that detected in many natural and engineered aquatic ecosystems. The presented data suggest the ecophysiological relevance of Novosphingobium spp. in activated sludge.IMPORTANCE Estrogens, which persistently contaminate surface water worldwide, have been classified as endocrine disruptors and human carcinogens. We contribute new knowledge on the major estrogen biodegradation pathway and estrogen degraders in wastewater treatment plants. This study considerably advances the understanding of environmental estrogen biodegradation, which is instrumental for the efficient elimination of these hazardous pollutants. Moreover, this study substantially improves the understanding of microbial estrogen degradation in the environment.

Demographic profile and ocular characteristics of stage 5 retinopathy of prematurity at a referral center in Northwest China: implications for implementation.

BACKGROUND: Severe retinopathy of prematurity (ROP) with extremely unfavorable prognosis among infants can do great damage to individuals and bring tremendous social-economic burden. The purpose of this study is to describe the demographic and ocular characteristics of infants who presented with stage 5 ROP in order to identify reasons why they have become blind, and to identify contributing factors in order to focus great attention on the current ROP program and to inspire more effort in ROP screening in middle income countries. METHODS: A retrospective review of consecutive infants with stage 5 ROP from December 2010 to December 2016 in Department of Ophthalmology, Xijing Hospital. Various parameters retrieved included birthweight, gestational age, age at initial examination, postmenstrual age, screening details, check-up details and reasons for consultation. Ocular findings were recorded and also detected by ultrasonography. RESULTS: A retrospective review of 20 consecutive infants with stage 5 ROP are included. Mean birthweight was1712.3 ± 512.97 g and mean gestational age at birth was 32.1 ± 2.21 weeks. Median age at first consultancy was 9.7 month. Median postmenstrual age first consultancy was 52 weeks. All infants were never screened for ROP before they came to the referral center. Of twenty stage 5 ROP infants, 13 cases presented with bilateral stage 5 features. Of the 40 eyes of 20 infants, 33 eyes were diagnosed as stage 5. Leukocoric pupil, closed funnel configuration of retinal detachment (RD), posterior synechia, extraretinal fibrovascular proliferation and retinal folds were the most significant indicators of bad prognosis. Ten eyes appeared no fixation to light, while 30 eyes exhibited following to light or following to toys. CONCLUSIONS: Our study shows that in relatively less-developed regions of China, more needs to be done to spread awareness about the disease among pediatricians, neonatologists and ophthalmologists as well as parents of premature infants. Thus, a comprehensive control system which is a whole network of propaganda, screening, treatment and follow-up are encouraged especially in less developed areas in China as well as worldwide.

Up-regulated basigin-2 in microglia induced by hypoxia promotes retinal angiogenesis.

Retinal microglia cells contribute to vascular angiogenesis and vasculopathy induced by relative hypoxia. However, its concrete molecular mechanisms in shaping retinal angiogenesis have not been elucidated. Basigin, being involved in tumour neovasculogenesis, is explored to exert positive effects on retinal angiogenesis induced by microglia. Therefore, we set out to investigate the expression of basigin using a well-characterized mouse model of oxygen-induced retinopathy, which recapitulated hypoxia-induced aberrant neovessel growth. Our results elucidate that basigin is overexpressed in microglia, which accumulating in retinal angiogenic sprouts. In vitro, conditioned media from microglia BV2 under hypoxia treatment increase migration and tube formation of retinal capillary endothelia cells, compared with media from normoxic condition. The angiogenic capacity of BV2 is inhibited after basigin knockdown by small interfering RNAs. A new molecular mechanism for high angiogenic capacity, whereby microglia cells release basigin via up-regulation of PI3K-AKT and IGF-1 pathway to induce angiogenesis is unveiled. Collectively, our results demonstrate that basigin from hypoxic microglia plays a pivotal pro-angiogenic role, providing new insights into microglia-promoting retinal angiogenesis.

Macrophages promote vasculogenesis of retinal neovascularization in an oxygen-induced retinopathy model in mice.

To investigate the role of macrophages in oxygen-induced retinal neovascularization (NV) in mice, particularly the involvement of bone marrow-derived cells (BMCs) and the underlying mechanisms, BMCs from green fluorescent protein (GFP) transgenic mice were transplanted into postnatal day (P) 1 mice after irradiation. The mice were exposed to 75 % oxygen from P7 to P12 to initiate oxygen-induced retinopathy (OIR). The macrophages were depleted by injection of clodronate-liposomes (lip) intraperitoneally. The eyes were collected at P12 and P17. Retinal flatmounts and histopathological cross-sections were performed to analyze the severity of retinal NV and BMC recruitment. BMCs immunopositive for CD31 (PECAM-1; endothelial cell marker) and α-SMA (smooth muscle cell marker) antigens were detected using a confocal microscope. Expression of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1) mRNA was detected by RT-PCR. The VEGF, SDF-1, CXCR4 and CD45 protein expression was detected by western blot examination. The retinal avascular area in OIR mice at P12 was unaffected after macrophage depletion carried out twice (38.27 ± 1.92 % reduction) using clodronate-lip. The retinal avascular area and the NV area at P17 were reduced after macrophage depletion four times (79.53 ± 1.02 % reduction); these findings were supported by retinal flatmounts and histopathological cross-sections. Macrophage depletion led to significant inhibition of BMC recruitment into the NV tufts at P17, with decreased expression of retinal VEGF, SDF-1, CXCR4 and CD45. The recruited BMCs differentiated primarily into CD31-positive endothelial cells (ECs) and α-SMA-positive smooth muscle cells (SMCs). This study suggested that macrophages promoted the vasculogenesis of retinal NV, particularly the contribution of BMCs in the mouse OIR model, which might be triggered by VEGF and SDF-1 production.

[Which one is more important, raw materials or productive technology?--a case study for quality consistency control of Gegen Qinlian decoction].

To investigate the effect of Chinese medicine raw materials and production technology on quality consistency of Chinese patent medicines with Gegen Qinlian decoction as an example, and establish a suitable method for the quality consistency control of Chinese patent medicines. The results showed that the effect of production technology on the quality consistency was generally not more than 5%, while the effect of raw materials was even more than 30%, indicating that the effect of raw materials was much greater than that of the production technology. In this study, blend technology was used to improve the quality consistency of raw materials. As a result, the difference between the product produced by raw materials and reference groups was less than 5%, thus increasing the quality consistence of finished products. The results showed that under the current circumstances, the main factor affecting the quality consistency of Chinese patent medicines was raw materials, so we shall pay more attention to the quality of Chinese medicine's raw materials. Finally, a blend technology can improve the quality consistency of Chinese patent medicines.

Hyperglycemia promotes vasculogenesis in choroidal neovascularization in diabetic mice by stimulating VEGF and SDF-1 expression in retinal pigment epithelial cells.

To investigate the influence of hyperglycemia on the severity of choroidal neovascularization (CNV) in diabetic mice, especially the involvement of bone marrow-derived cells (BMCs) and underlying molecular mechanisms. The mice were randomly divided into control group, diabetes group and diabetes treated with insulin group, which were laser treated to induce CNV. The CNV severity was evaluated by fundus fluorescein angiography, HE staining and choroidal flatmount. The BMCs recruitment and differentiation in CNV were examined in GFP chimeric mice by choroidal flatmount and immunofluorescence. The bone marrow-derived mesenchymal stem cells (BMSCs) recruitment and migration were tested in vivo and in vitro. VEGF and SDF-1 production in vivo and in vitro were tested by realtime PCR and ELISA. The CNV severity and expression of VEGF and SDF-1 were enhanced in DM mice compared with control mice and that insulin treatment decreased CNV severity in DM mice. The DM mice demonstrated more BMCs and bone marrow-derived mesenchymal stem cells (BMSCs) recruited and incorporated into CNV, increased ratio of BMCs expressing endothelial cell marker or macrophage marker, and up-regulated expression of VEGF and SDF-1 in CNV. Human BMSCs migration and expression of VEGF and SDF-1 in retinal pigment epithelial (RPE) cells increased when cultured under high glucose. This study suggested that hyperglycemia enhanced the expression of VEGF and SDF-1 in RPE cells, and promoted recruitment and incorporation of BMCs and affected differentiation of BMCs in CNV, which led to more severe CNV in diabetic mice.

Effects of wheat protein on hot-extrusion 3D-printing performance and the release behaviours of caffeic acid-loaded wheat starch.

In this study, the effects of wheat protein (WP) on the hot-extrusion 3D-printing (HE-3DP) performance of wheat starch (WS) gels, as well as effects of such gels on the encapsulation of caffeic acid, were investigated for the first time. The HE-3DP results show that the addition of WP can reduce print-line width and improve printing accuracy and fidelity, and the best printing results were achieved when using gels with 10 % WP. The rheological results show that WP reduced the gels' linear viscoelastic region (LVR), yield stress (τy), flow stress (τf) and consistency factor (K) but increased their structural recovery rate, which facilitated smooth extrusion during 3D printing and, thus, improved printing accuracy. The analysis of X-ray diffraction and small-angle X-ray scattering indicates that adding WP to WS could increase the mass fractal dimension and lead to denser gel network structures. The results regarding release kinetics demonstrate that the maximum release of caffeic acid from gels decreased by 28 % with the addition of WP, indicating slow-release behaviour. This study provided valuable information about processing wheat products via 3D printing.

Multivariate prognostic index and triplet regimen efficacy predictive index in locally advanced and metastatic gastric cancer: pooled analysis from three clinical trials using individual patient data.

Background: To construct an effective prognostic index to predict overall survival (OS) and triplet regimen efficacy for advanced gastric cancer (AGC) patients treated with platinum-based and fluorouracil-based chemotherapy. Objectives: Between 2011 and 2021, 679 patients from two randomized phase III trials and one phase II trial were enrolled. Designs: We collected 11 baseline clinicopathological and 14 hematological parameters to establish a prognostic index. Methods: Univariate and multivariate Cox analyses were used to screen prognostic factors, and a prognostic index nomogram was conducted. Results: Seven prognostic factors were identified: primary tumor site in the non-proximal gastric area, signet-ring cell carcinoma (SRCC)/mucinous carcinoma, peritoneal metastasis, neutrophil count higher than the upper limit of normal value (ULN), lymphocyte count lower than the lower limit of normal value, lactate dehydrogenase level higher than the ULN, and alkaline phosphatase level higher than the ULN as significant for prognosis. A prognostic nomogram named the Fudan advanced gastric cancer prognostic risk score (FARS) index was constructed, and patients in the high-risk group had significantly shorter OS than those in the low-risk group (median OS, 15.5 versus 8.0 months, p < 0.001). The areas under the curve of the FARS index for 1-, 2-, and 3-year OS were 0.70, 0.72, and 0.77, respectively. A validation and external cohort verified the prognostic value of the FARS index. Moreover, three triplet regimen efficacy parameters were identified: SRCC/mucinous adenocarcinoma, primary tumor location in the non-proximal gastric area, and peripheral neutrophil count higher than the ULN; a TRIS index was subsequently conducted. In patients with any two of the three parameters, the triplet regimen showed significantly longer OS than the doublet regimen (p = 0.018). Conclusion: The constructed FARS index to predict the OS of AGC patients and the TRIS index to screen out the dominant population for triplet regimens can be used to aid clinical decision-making and individual risk stratification.

A prognostic index in locally advanced and metastatic gastric cancer To date, no recognized systematic prognostic score has been established for advanced gastric cancer (AGC). Our research aims to construct an effective prognostic index to predict overall survival (OS) for AGC patients to aid clinical decision-making and individual risk stratification. In our research, seven prognostic factors were identified: primary tumor site in the non-proximal gastric area, signet-ring cell carcinoma (SRCC)/mucinous carcinoma, peritoneal metastasis, neutrophil count higher than the upper limit of normal value (ULN), lymphocyte count lower than the lower limit of normal value, lactate dehydrogenase level higher than the ULN, and alkaline phosphatase level higher than the ULN as significant for prognosis. A prognostic index named the Fudan advanced gastric cancer prognostic risk score (FARS) index was constructed, and patients in the high-risk group had significantly shorter OS than those in low-risk group (median OS, 15.5 months vs. 8.0 months, P < 0.001). Moreover, three triplet regimen efficacy parameters were identified: SRCC/mucinous adenocarcinoma, primary tumor location in the non-proximal gastric area, and peripheral neutrophil count higher than the ULN; a TRIS index was subsequently conducted. In patients with any two of the three parameters, the triplet regimen showed significantly longer OS than the doublet regimen (P = 0.018).

An angiotensin-converting enzyme inhibitor modulates stromal-derived factor-1 through CD26/dipeptidyl peptidase IV to inhibit laser-induced choroidal neovascularization.

PURPOSE: Stromal-derived factor (SDF)-1 is a chemokine that recruits bone marrow-derived endothelial precursor cells (EPCs) for choroidal neovascularization (CNV) development. Angiotensin-converting enzyme (ACE) inhibitors mediate the compensatory effects of ACE and CD26/dipeptidyl peptidase IV (DPP IV), which results in the degradation and inactivation of SDF-1 in vivo. ACE inhibitors, such as imidapril, exhibit potential antiangiogenic effects on laser-induced CNV in mice. The role that this imidapril-mediated effect plays in modulating SDF-1 signals has not been defined. The present study assessed the effect of the CD26/SDF-1 signaling pathway on the inhibitory effect of imidapril in CNV development. METHODS: CNV was induced in C57BL/6J mice by focally rupturing Bruch's membrane using a 532-nm diode laser. The animals were pretreated with PBS, imidapril, diprotin-A (a DPP IV antagonist), or imidapril plus diprotin-A for 5 days before photocoagulation. Treatments were continued daily for 14 days following the laser induction. The normal control group did not undergo laser rupture or receive treatment. CD26 activity was measured using a substrate conversion assay and flow cytometry. SDF-1 levels in both the blood and the bone marrow were measured using an enzyme-linked immunosorbent assay, and the number of circulating endothelial progenitor cells (EPCs) and leukocytes was quantified. Functional analyses of circulating SDF-1 were performed using actin polymerization blood biomarker assays, and the CNV-related responses were evaluated using fluorescein angiography and isolectin-B4-labeled flatmounts. RESULTS: Imidapril directly amplified CD26 activity and had a minor effect on the number of CD26+ cells in the bone marrow. However, decreased CD26 activity in the plasma was secondary to a decrease in the number of circulating CD26+ cells and blood leukocytes. Furthermore, imidapril increased SDF-1 concentrations in the peripheral circulation via CD26-induced degradation of SDF-1 in the bone marrow, an effect that coincided with elevated numbers of circulating EPCs. CD26-mediated SDF-1 inactivation was demonstrated by a decrease in SDF-1-induced actin polymerization in the whole blood of imidapril-treated mice. Imidapril markedly decreased angiographic leakage and CNV size. CD26 inhibition completely blocked the CD26/SDF-1 signaling pathway in vivo and reduced the antiangiogenic effect of imidapril. CONCLUSIONS: These results strongly suggest that the antiangiogenic effects of imidapril on laser-induced CNV partially involve the modulation of the CD26/SDF-1 signaling pathway.

Preliminary study of retinal pathological features in preterm birth pups exposed to an animal model of oxygen-induced retinopathy in mice.

BACKGROUND: The main risk factors of retinopathy of prematurity (ROP) are low gestational age and low birth weight, which are mainly caused by preterm birth. Currently, the animal model of oxygen-induced retinopathy (OIR) in mice is the most widely used model in ROP-associated studies. However, the experimental mice are normal-term pups, and may not mimic the pathogenic status of human ROP patients. In this study, we investigated the retinal pathological features in preterm birth pups exposed to an animal model of oxygen-induced retinopathy in mice. METHODS: Preterm-birth mice were obtained from pregnant C57BL/6J mice that were induced by an intraperitoneal injection of lipopolysaccharide (LPS). The preterm and control mice were treated with high oxygen (75%) from postnatal day 7 (P7) to P12. The mice were perfused with high-molecular-weight FITC-dextran on P12, P15 and P17, and the retinas were whole-mounted and imaged. Vascular endothelial growth factor (VEGF) mRNA was also detected. Cross-sections of the retina were stained with hematoxylin and eosin (H&E) to identify preretinal neovascular tufts. For general observation, whole retinal images were also obtained using a microscope. RESULTS: Leakage of the retinal blood vessels was aggravated in the preterm mice, particularly on P12 and P15. The non-perfused areas of the retina (pixel value, 183,673 ± 28,148 vs 132,110 ± 23,732, P = 0.009) and the number of preretinal endothelial cell nuclei were smaller (30.17 ± 8.33 vs 22.17 ± 6.74, P < 0.0001) on P17. The VEGF mRNA levels in the retinas were higher on P12 and P15 but lower on P17, compared with the control mice. Retinal hemorrhage was observed in the preterm mouse group (five out of six examined eyes). CONCLUSIONS: Preterm-birth mice that were subject to OIR exhibited several pathological features, such as retinal hemorrhage, severe retinal leakage and moderate retinal neovascularization, which were similar to the clinical manifestations in ROP patients.

In-vivo investigation of laser-induced choroidal neovascularization in rat using spectral-domain optical coherence tomography (SD-OCT).

PURPOSE: This study investigated the in-vivo formation process of laser-induced choroidal neovascularization (CNV) in rat using high-resolution spectral-domain optical coherence tomography (SD-OCT), and compared the results to histological methods. METHODS: Brown Norway rats (n = 60, 6-8 weeks of age) received 532-nm diode laser photocoagulation. SD-OCT and fluorescein angiography (FA) were performed in vivo 2, 5, 7, 14, and 21 days post-laser application. Haematoxylin and eosin (H&E) staining and immunohistochemistry for CD31, phosphorylated vascular endothelial factor receptor 2 (pVEGFR2) were conducted at each time point to observe the CNV in vitro. Choroidal flatmount preparations were observed using a confocal laser scanning microscope (CLSM) and a scanning electron microscope (SEM). RESULTS: SD-OCT monitored the longitudinal morphological changes of laser-induced CNV. CNV reached its maximal size on day 7, and began a gradual reduction on day 14. FA revealed similar dynamic changes in leakage. CNV thickness, as assessed by SD-OCT, was consistent with H&E-stained sections at each time point. CLSM and SEM revealed the details of the fibrovascular membrane. CD31 and pVEGFR2 expression supported the results of SD-OCT and histology. CONCLUSIONS: SD-OCT was a convenient and reliable tool for the imaging of the CNV formation process and quantification of the lesion size in vivo.

[Identification and early diagnosis of choroideremia and gyrate atrophy].

Choroideremia and gyrate atrophy are two kinds of heritage primary retino-choroidal atrophy diseases. At advanced stage, their typical fundus lesions are conductive to identification. However, early diagnosis and intervention, which lead to improved prognosis and genetic benefits, are hindered by some similar clinical manifestation and optical examine results. Therefore, it is meaningful for ophthalmologists to have a comprehensive understand of these two diseases, and provide early diagnosis and proper intervention including genetic consultation.

[Effect of premature birth on retinal vascular development in the neonatal rat].

OBJECTIVE: To study the effects of premature birth on the development of rat retinal vasculature. METHODS: Experimental study. Sixty pregnant Sprague-Dawley rats were divided into four groups: bacterial lipopolysaccharide-induced preterm group (LPS group), RU-486 induced preterm group (RP group), cesarean section induced preterm group (CP group), and the normal delivery rats as the control group. The weight of rats from each group was recorded until postnatal day 21. On postnatal day 4, 7, 10 and 14 (P4, P7, P10 and P14), the retina of right eye was dissected and whole-mounted. Each premature group was divided into two subgroups based on the number of rats in each litter, the small subgroup (6-8 rats per litter, group 1) and the large subgroup (14-18 rats per litter, group 2). The development of retinal vascularization process was observed on P4, P7 and P10 (n = 6).Independent t test, one-way ANOVA and LSD-t test were used to analyzed the results. RESULTS: The weight of premature rats in LPS, CP and RP groups was significantly lower than that in the normal group within postnatal 21 days (LSD-t test: all P < 0.05). On the P4 and P7 in LPS group, the proportions of retinal superficial vascularized area of newborn rats [(0.47 ± 0.02) % ,(0.63 ± 0.04)%] were less than that in the normal group [(0.57 ± 0.04) % , (0.74 ± 0.05)%] (t4 d = 6.427, P 4 d = 0.000;t7 d = 5.111, P 7 d = 0.000). On the P4 and P7 in RP group, this proportions [(0.49 ± 0.04) %,(0.65 ± 0.04)%] were less than that in the normal group [(0.57 ± 0.04) %, (0.74 ± 0.05)%] (t4 d = 4.469, P 4 d = 0.000;t7 d = 2.491, P 7 d = 0.022). On P4, P7 and P10 in CP group, this proportions [(0.49 ± 0.05) %, (0.61 ± 0.05) %, (0.94 ± 0.03)%] were also less than that in the normal group[ (0.57 ± 0.04) %, (0.74 ± 0.05) %, (0.97 ± 0.02)%] (t4 d = 4.044, P 4 d = 0.001;t7 d = 6.011, P 7 d = 0.000; t 10 d = 2.331, P 10 d = 0.030). Retinal superficial vascularization completed on P14 in all groups. On the P4 and P7 in LPS group, the proportion of retinal vascularized area of group 2 [(0.44 ± 0.02)%, (0.60 ± 0.03)%] were less than that of group 1 [(0.53 ± 0.04)%, (0.74 ± 0.03)%] (t4 d = 3.852, P 4 d = 0.008; t7 d = 5.630, P 7 d = 0.001). On the P4 and P7 in CP group, this proportion in group 2 [(0.43 ± 0.02)%, (0.64 ± 0.03)%] were less than that of group 1 [ (0.54 ± 0.03)%, (0.76 ± 0.02)%] (t4 d = 4.695, P 4 d = 0.003; t7 d = 6.025, P 7 d = 0.001). On P4 in RP group, the proportions of group 2 [ (0.44 ± 0.01)%] was less than that of group 1 [ (0.54 ± 0.04)%] (t4 d = 5.000, P 4 d = 0.002). CONCLUSIONS: The premature rats have lower weight and much slower rate of early retinal vascularization, as compared with the normal rats. Furthermore, in the premature rats, the proportion of retinal vascularization in larger litters is less than that in smaller litters. These results indicate that premature birth and larger litter size have effects on the development of rat retinal vasculature.