The competitive endogenous RNA regulatory network reveals potential prognostic biomarkers for overall survival in hepatocellular carcinoma.

The aim of the present study is to construct a competitive endogenous RNA (ceRNA) regulatory network by using differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in patients with hepatocellular carcinoma (HCC), and to construct a prognostic model for predicting overall survival (OS) of HCC patients. Differentially expressed lncRNAs, miRNAs, and mRNAs were explored between HCC tissues and normal liver tissues. A prognostic model was built for predicting OS of HCC patients and receiver operating characteristic curves were used to evaluate the performance of the prognostic model. There were 455 differentially expressed lncRNAs, 181 differentially expressed miRNAs, and 5035 differentially expressed mRNAs. A ceRNA regulatory network was constructed based on 43 lncRNAs, 37 miRNAs, and 105 mRNAs. Eight mRNA biomarkers (H2AFX, SQSTM1, ITM2A, PFKP, TPD52L1, ACSL4, STRN3, and CPEB3) were identified as independent risk factors by multivariate Cox regression and were used to develop a prognostic model for OS. The C-indexes in the model group were 0.776 (95% confidence interval [CI], 0.730-0.822), 0.745 (95% CI, 0.699-0.791), and 0.789 (95% CI, 0.743-0.835) for 1-, 3-, and 5-year OS, respectively. The current study revealed potential molecular biological regulation pathways and prognostic biomarkers by the ceRNA regulatory network. A prognostic model based on prognostic mRNAs in the ceRNA network might be helpful to predict the individual mortality risk for HCC patients. The individual mortality risk calculator can be used by visiting the following URL: https://zhangzhiqiao.shinyapps.io/Smart_cancer_predictive_system_HCC/.

Two precision medicine predictive tools for six malignant solid tumors: from gene-based research to clinical application.

BACKGROUND: The current study aimed to construct competing endogenous RNA (ceRNA) regulation network and develop two precision medicine predictive tools for colorectal cancer (CRC). METHODS: Differentially expressed (DE) analyses were performed between CRC tissues and normal tissues. A ceRNA regulation network was constructed based on DElncRNAs, DEmiRNAs, and DEmRNAs. RESULTS: Fifteen mRNAs (ENDOU, MFN2, FASLG, SHOC2, VEGFA, ZFPM2, HOXC6, KLK10, DDIT4, LPGAT1, BEX4, DENND5B, PHF20L1, HSP90B1, and PSPC1) were identified as prognostic biomarkers for CRC by multivariate Cox regression. Then a Fifteen-mRNA signature was developed to predict overall survival for CRC patients. Concordance indexes were 0.817, 0.838, and 0.825 for 1-, 2- and 3-year overall survival. Patients with high risk scores have worse OS compared with patients with low risk scores. CONCLUSION: The current study provided deeper understanding of prognosis-related ceRNA regulatory network for CRC. Two precision medicine predictive tools named Smart Cancer Survival Predictive System and Gene Survival Analysis Screen System were constructed for CRC. These two precision medicine predictive tools can provide valuable precious individual mortality risk prediction before surgery and improve the individualized treatment decision-making.

Comprehensive bioinformatics analysis reveals potential lncRNA biomarkers for overall survival in patients with hepatocellular carcinoma: an on-line individual risk calculator based on TCGA cohort.

BACKGROUND: Accumulated evidences have demonstrated that long non-coding RNAs (lncRNAs) are correlated with prognosis of patients with hepatocellular carcinoma. The current study aimed to develop and validate a prognostic lncRNA signature to improve the prediction of overall survival in hepatocellular carcinoma patients. METHODS: The study cohort involved 348 hepatocellular carcinoma patients with lncRNA expression information and overall survival information. Through gene mining approach, the current study established a prognostic lncRNA signature (named LncRNA risk prediction score) for predicting the overall survival of hepatocellular carcinoma patients. RESULTS: The current study built a predictive nomogram based on ten prognostic lncRNA predictors through Cox regression analysis. In model group, the Harrell's concordance indexes of LncRNA risk prediction score were 0.811 (95% CI 0.769-0.853) for 1-year overall survival, 0.814 (95% CI 0.772-0.856) for 3-year overall survival and 0.796 (95% CI 0.754-0.838) for 5-year overall survival respectively. In validation cohort, the Harrell's concordance indexes of LncRNA risk prediction score were 0.779 (95% CI 0.737-0.821), 0.828 (95% CI 0.786-0.870) and 0.796 (95%CI 0.754-0.838) for 1-year survival, 3-year survival and 5-year survival respectively. LncRNA risk prediction score could stratify hepatocellular carcinoma patients into low risk group and high risk group. Further survival curve analysis demonstrated that the overall survival rate of high risk patients was significantly poorer than that of low risk patients (P < 0.001). CONCLUSIONS: In conclusion, the current study developed and validated a prognostic signature to predict the individual mortality risk for hepatocellular carcinoma patients. LncRNA risk prediction score is helpful to identify the patients with high mortality risk and optimize the individualized treatment decision. The web calculator can be used by click the following URL: https://zhangzhiqiao2.shinyapps.io/Smart_cancer_predictive_system_HCC_3/.

Two predictive precision medicine tools for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a serious threat to public health due to its poor prognosis. The current study aimed to develop and validate a prognostic nomogram to predict the overall survival of HCC patients. METHODS: The model cohort consisted of 24,991 mRNA expression data points from 348 HCC patients. The least absolute shrinkage and selection operator method (LASSO) Cox regression model was used to evaluate the prognostic mRNA biomarkers for the overall survival of HCC patients. RESULTS: Using multivariate Cox proportional regression analyses, a prognostic nomogram (named Eight-mRNA prognostic nomogram) was constructed based on the expression data of N4BP3, -ADRA2B, E2F8, MAPT, PZP, HOXD9, COL15A1, and -NDST3. The C-index of the Eight-mRNA prognostic nomogram was 0.765 (95% CI 0.724-0.806) for the overall survival in the model cohort. The Harrell's concordance-index of the Eight-mRNA prognostic nomogram was 0.715 (95% CI 0.658-0.772) in the validation cohort. The survival curves demonstrated that the HCC patients in the high risk group had a significantly poorer overall survival than the patients in the low risk group. CONCLUSION: In the current study, we have developed two convenient and efficient predictive precision medicine tools for hepatocellular carcinoma. These two predictive precision medicine tools are helpful for predicting the individual mortality risk probability and improving the personalized comprehensive treatments for HCC patients. The Smart Cancer Predictive System can be used by clicking the following URL: https://zhangzhiqiao2.shinyapps.io/Smart_cancer_predictive_system_HCC_2/. The Gene Survival Analysis Screen System is available at the following URL: https://zhangzhiqiao5.shinyapps.io/Gene_Survival_Analysis_A1001/.

Retinal vessel diameter measurements by spectral domain optical coherence tomography.

PURPOSE: To describe a spectral domain optical coherence (OCT)-assisted method of measuring retinal vessel diameters. METHODS: All Patients with an OCT circle scan centered at the optic nerve head using a Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) were retrospectively reviewed. Individual retinal vessels were identified on infrared reflectance (IR) images and given unique labels both on IR and spectral domain OCT (SD-OCT). Vessel width and vessel types obtained by IR were documented as ground truth. From OCT, measurements of each vessel, including horizontal vessel contour diameter, vertical vessel contour diameter, horizontal hyperreflective core diameter, and reflectance shadowing width, were assessed. RESULTS: A total of 220 vessels from 13 eyes of 12 patients were labeled, among which, 194 vessels (88 arteries and 65 veins confirmed from IR) larger than 40 microns were included in the study. The mean vessel width obtained from IR was 107.9 ± 36.1 microns. A mean vertical vessel contour diameter of 119.6 ± 29.9 microns and a mean horizontal vessel contour diameter of 124.1 ± 31.1 microns were measured by SD-OCT. Vertical vessel contour diameter did not differ from vessel width in all subgroup analysis. Horizontal vessel contour diameter was not significantly different from vessel width for arteries and had strong or very strong correlation with vessel width for veins. CONCLUSION: In our study, vertical vessel contour diameter measured by current commercially available SD-OCT was consistent with vessel width obtained by IR with good reproducibility. This SD-OCT based method could potentially be used as a standard measurement procedure to evaluate retinal vessel diameters and their changes in ocular and systemic disorders.

Postoperative anatomical and functional outcomes of different stages of high myopia macular hole.

BACKGROUND: Recently it was suggested that high myopia macular holes (HMMH) and macular holes accompanied by retinal detachment occur in the advanced stages of myopia traction maculopathy (MTM), while macular retinoschisis, shallow retinal detachment without holes, and lamellar macular holes occur in the early stages of MTM. Complete vitreous cortex removal associated with internal limiting membrane peeling is now widely used to treat HMMH. However, it remains uncertain at what HMMH stage patients would benefit most from surgical intervention. Our study was aimed to evaluate the postoperative anatomical changes and functional outcomes of high myopia macular holes (HMMH). METHODS: Patients were retrospectively collected between March 2009 and August 2011. Before and 1st, 3rd, and 9th month after 23G pars plana vitrectomy, all patients underwent a complete ophthalmologic examination, spectral domain optical coherence tomography (SD-OCT) and MP-1. At each follow-up, best-corrected visual acuity (BCVA), photoreceptor inner and outer segments (IS/OS) defects, and retinal sensitivity (RS) were investigated. According to different preoperative macular hole morphologies, patients were divided into three groups: Group 1, macular hole with epiretinal membrane (ERM) traction and macular retinoschisis; Group 2, full-thickness macular hole (FTMH); Group 3, FTMH with subretinal fluid. RESULTS: 43 eyes from 43 patients met the inclusion criteria. The mean age was 60 years. BCVA and RS were significantly improved after vitrectomy; the mean IS/OS defect was significantly reduced. At 9 postoperative months, 11 of 43 (25.6 %) eyes achieved IS/OS junction integrity; 9 of these 11 (81.8 %) eyes belonged to Group 1, 2 (18.2 %) belonged to Group 2. CONCLUSIONS: Pars plana vitrectomy combined with ILM peeling and gas tamponade results in limited functional outcomes in patients with HMMH. The appearance of subretinal fluid indicates a worse prognosis for surgical intervention.

Clinical outcomes after switching treatment from intravitreal ranibizumab to aflibercept in neovascular age-related macular degeneration.

PURPOSE: To describe the treatment response to aflibercept in patients with exudative age-related macular degeneration that showed insufficient or diminishing treatment effects under ranibizumab. METHODS: From December 2012 till June 2013 all patients receiving intravitreal injections of aflibercept after previous treatment with ranibizumab were collected in a database and retrospectively reviewed. Clinical data such as visual acuity or central subfield retinal thickness on optical coherence tomography (OCT) scans were analyzed for the time frame before, during, and shortly after the aflibercept injections. Of particular interest was the comparison of clinical features under ongoing ranibizumab treatment to the time during aflibercept treatment. RESULTS: Seventy-one eyes of 65 patients were included in the study. All eyes had previous ranibizumab injections in their medical history, the average number of which was nine (range 3-43). For the total group the mean visual acuity (VA) before the first ranibizumab injection was 0.54 logMAR, and after the last ranibizumab injection was 0.57 logMAR. Mean VA changed from 0.47 logMAR before the first aflibercept injection to 0.25 logMAR after the last aflibercept injection. Central subfield retinal thickness (CSRT) on OCT changed from a mean of 417.28 µm to 349.52 µm under ranibizumab treatment and from 338.76 µm to 272.00 µm under aflibercept treatment. Interestingly, 33 % of cases that did not show a functional improvement under ranibizumab therapy gained visual acuity after aflibercept treatment. CONCLUSION: Aflibercept appears to be an effective choice for patients with neovascular age-related macular degeneration who were resistant to previous therapy of ranibizumab. The longevity of this effect still remains questionable.

An easy method to differentiate retinal arteries from veins by spectral domain optical coherence tomography: retrospective, observational case series.

BACKGROUND: Recently it was shown that retinal vessel diameters could be measured using spectral domain optical coherence tomography (OCT). It has also been suggested that retinal vessels manifest different features on spectral domain OCT (SD-OCT) depending on whether they are arteries or veins. Our study was aimed to present a reliable SD-OCT assisted method of differentiating retinal arteries from veins. METHODS: Patients who underwent circular OCT scans centred at the optic disc using a Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) were retrospectively reviewed. Individual retinal vessels were identified on infrared reflectance (IR) images and given unique labels for subsequent grading. Vessel types (artery, vein or uncertain) assessed by IR and/or fluorescein angiography (FA) were referenced as ground truth. From OCT, presence/absence of the hyperreflective lower border reflectivity feature was assessed. Presence of this feature was considered indicative for retinal arteries and compared with the ground truth. RESULTS: A total of 452 vessels from 26 eyes of 18 patients were labelled and 398 with documented vessel type (302 by IR and 96 by FA only) were included in the study. Using SD-OCT, 338 vessels were assigned a final grade, of which, 86.4% (292 vessels) were classified correctly. Forty three vessels (15 arteries and 28 veins) that IR failed to differentiate were correctly classified by SD-OCT. When using only IR based ground truth for vessel type the SD-OCT based classification approach reached a sensitivity of 0.8758/0.9297, and a specificity of 0.9297/0.8758 for arteries/veins, respectively. CONCLUSION: Our method was able to classify retinal arteries and veins with a commercially available SD-OCT alone, and achieved high classification performance. Paired with OCT based vessel measurements, our study has expanded the potential clinical implication of SD-OCT in evaluation of a variety of retinal and systemic vascular diseases.

Optical coherence tomography-based observation of the natural history of drusenoid lesion in eyes with dry age-related macular degeneration.

PURPOSE: To use spectral domain optical coherence tomography (SD-OCT) to investigate risk factors predictive for the development of atrophy of drusenoid lesions (DLs) (drusen and drusenoid pigment epithelium detachment) in eyes with non-neovascular age-related macular degeneration (NNVAMD). DESIGN: Cohort study. PARTICIPANTS: Forty-one eyes from 29 patients with NNVAMD. METHODS: Patients with NNVAMD who underwent registered SD-OCT imaging over a minimum period of 6 months were reviewed. Drusenoid lesions that were accompanied by new atrophy onset at 6 months or last follow-up (FUL) were further analyzed. Detailed lesion change was described throughout the study period. Odds ratios (ORs) and risk for new local atrophy onset were calculated. MAIN OUTCOME MEASURES: Drusenoid lesion features and longitudinal changes in features, including maximum lesion height, lesion diameter, lesion internal reflectivity, and presence and extent of overlying intraretinal hyperreflective foci (HRF). Subfoveal choroidal thickness (SFCT) and choroidal thickness (CT) were measured below each lesion. RESULTS: A total of 543 individual DLs were identified at baseline, and 28 lesions developed during follow-up. The mean follow-up time was 21.3±8.6 months (range, 6-44 months). Some 3.2% of DLs (18/571) progressed to atrophy within 18.3 ± 9.5 months (range, 5-28 months) of the initial visit. Drusenoid lesions with heterogeneous internal reflectivity were significantly associated with new atrophy onset at 6 months (OR, 5.614; 95% confidence interval [CI], 1.277-24.673) and new atrophy onset at FUL (OR, 7.005; 95% CI, 2.300-21.337). Lesions with the presence of HRF were significant predictors of new atrophy onset at 6 months (OR, 30.161; 95% CI, 4.766-190.860) and FUL (OR, 11.211; 95% CI, 2.513-50.019). Lesions with a baseline maximum height >80 µm or CT ≤ 135 µm showed a positive association with the new atrophy onset at FUL (OR, 7.886; 95% CI, 2.105-29.538 and OR, 3.796; 95% CI, 1.154-12.481, respectively). CONCLUSIONS: The presence of HRF overlying DLs, a heterogeneous internal reflectivity of these lesions, was found consistently to be predictive of local atrophy onset in the ensuing months. These findings provide further insight into the natural history of anatomic change occurring in patients with NNVAMD.

Different phenotypes of the appearance of the outer plexiform layer on optical coherence tomography.

PURPOSE: To present a selected case series of different phenotypes of the normal outer plexiform layer (OPL) visualized by optical coherence tomography (OCT). METHODS: Five cases were selected to represent the spectrum of appearances of the OPL in this case series. Categorical descriptions of each manifestation were then developed. Additional SD-OCT scans were obtained from a normal volunteer to further support the hypothesis. RESULTS: The inner one-third of the OPL typically appears hyperreflective on OCT, while the outer two-thirds (Henle fiber layer) may have a more varied appearance. Six different phenotypes of Henle fiber layer reflectivity were noted in this series, and classified as: bright, columnar, dentate, delimited, indistinct, and dark. The brightness of the Henle fiber layer appears to depend on the geometric angle between the OCT light beam and the axonal fibers in this portion of the OPL. This angle appears to be a function of the natural orientation of the Henle fiber layer tissue (θN), the existence of subretinal pathology that alters the angle of the neurosensory retina (θ(P)), and the tilt angle of the tissue on the B-scan (θ(T)) due to decentered OCT acquisition. CONCLUSIONS: Since accurate interpretation of the OPL/ONL boundary is of vital importance to study the thickness of ONL, location of cystoid lesions, hyperreflective crescents over drusen, et al., our case series may aid better understanding of the OPL appearance in SD-OCT. In the absence of clear delineation, it may be most correct to refer to indistinct OPL and ONL together as the photoreceptor nuclear axonal complex (PNAC).

Evaluation of the axial location of cystoid spaces in retinal vein occlusion using optical coherence tomography.

PURPOSE: To analyze the axial distribution of intraretinal cystoid changes in patients with retinal vein occlusion (RVO), incorporating a new hypothesis about the optical coherence tomographic boundary between the outer nuclear layer and the outer plexiform layer. METHODS: Data were collected from patients with RVO who underwent spectral domain coherence tomography imaging. For each image set, certified graders evaluated each retinal layer for cystoid macular edema, defined as hyporeflective intraretinal cystoid spaces. Subretinal fluid, if present, was also noted. RESULTS: Forty-eight eyes were evaluated (24 branch RVO, 18 central RVO, 6 hemiretinal vein occlusion). Cystoid macular edema was present in 30.8% of eyes in outer nuclear layer, 77.9 % in outer plexiform layer, 77.9 % in inner nuclear layer, 36.9 % in inner plexiform layer, 48.8 % in ganglion cell layer, and 4.9% in nerve fiber layer. Subretinal fluid was assessed as present in 23.8% of patients. The presence of subretinal fluid correlated most strongly with cystoid changes in the outer nuclear layer (r = 0.514, P = 0.001) but was not significantly correlated with these changes in the superficial retina. CONCLUSION: Use of spectral domain coherence tomography allows precise characterization of the axial location of cystoid spaces in RVO and highlights the frequency of fluid accumulation in the outer plexiform layer and inner nuclear layer. Using updated definitions, cystoid macular edema seems to occur less frequently in the outer nuclear layer, but when it does so, it is often associated with subretinal fluid. Future longitudinal studies, documenting the axial progression of such changes, and their response to treatment, may be of clinical relevance as pharmacotherapeutic options evolve.

Real world outcomes of photodynamic therapy for chronic central serous chorioretinopathy.

OBJECTIVES: We describe the real-world outcomes of photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSCR) in a single centre over nine years. METHODS: We carried out a retrospective analysis of patients with chronic CSCR who received half dose PDT in a single centre between 2011 and 2019. Visual acuity (VA) and retinal thickness (RT) was recorded between baseline visit and first recorded review visit. RESULTS: We included 125 eyes of 113 patients in this study. Mean age at treatment was 55.0 ± 12.1 years, with a higher male predominance (83 men, 30 women). Mean baseline VA was 0.40 ± 0.31 logMAR with a mean visual outcome gain post-PDT of 0.05 logMAR (p = 0.005). Mean baseline RT was 390 ± 82 microns with a mean reduction of RT post-PDT of 66 microns (p < 0.001). 17.6% of eyes were treated for recurrent CSCR. CONCLUSION: We found overall a mean improvement in VA and structural outcomes after PDT. In the absence of randomised clinical trials this study supports the use of half dose PDT for treatment of chronic CSCR.

A Deep Learning Framework for the Detection and Quantification of Reticular Pseudodrusen and Drusen on Optical Coherence Tomography.

Purpose: The purpose of this study was to develop and validate a deep learning (DL) framework for the detection and quantification of reticular pseudodrusen (RPD) and drusen on optical coherence tomography (OCT) scans. Methods: A DL framework was developed consisting of a classification model and an out-of-distribution (OOD) detection model for the identification of ungradable scans; a classification model to identify scans with drusen or RPD; and an image segmentation model to independently segment lesions as RPD or drusen. Data were obtained from 1284 participants in the UK Biobank (UKBB) with a self-reported diagnosis of age-related macular degeneration (AMD) and 250 UKBB controls. Drusen and RPD were manually delineated by five retina specialists. The main outcome measures were sensitivity, specificity, area under the receiver operating characteristic (ROC) curve (AUC), kappa, accuracy, intraclass correlation coefficient (ICC), and free-response receiver operating characteristic (FROC) curves. Results: The classification models performed strongly at their respective tasks (0.95, 0.93, and 0.99 AUC, respectively, for the ungradable scans classifier, the OOD model, and the drusen and RPD classification models). The mean ICC for the drusen and RPD area versus graders was 0.74 and 0.61, respectively, compared with 0.69 and 0.68 for intergrader agreement. FROC curves showed that the model's sensitivity was close to human performance. Conclusions: The models achieved high classification and segmentation performance, similar to human performance. Translational Relevance: Application of this robust framework will further our understanding of RPD as a separate entity from drusen in both research and clinical settings.

Individual mortality risk predictive system of patients with acute-on-chronic liver failure based on a random survival forest model.

BACKGROUND: The basis of individualized treatment should be individualized mortality risk predictive information. The present study aimed to develop an online individual mortality risk predictive tool for acute-on-chronic liver failure (ACLF) patients based on a random survival forest (RSF) algorithm. METHODS: The current study retrospectively enrolled ACLF patients from the Department of Infectious Diseases of The First People's Hospital of Foshan, Shunde Hospital of Southern Medical University, and Jiangmen Central Hospital. Two hundred seventy-six consecutive ACLF patients were included in the present study as a model cohort (n = 276). Then the current study constructed a validation cohort by drawing patients from the model dataset based on the resampling method (n = 276). The RSF algorithm was used to develop an individual prognostic model for ACLF patients. The Brier score was used to evaluate the diagnostic accuracy of prognostic models. The weighted mean rank estimation method was used to compare the differences between the areas under the time-dependent ROC curves (AUROCs) of prognostic models. RESULTS: Multivariate Cox regression identified hepatic encephalopathy (HE), age, serum sodium level, acute kidney injury (AKI), red cell distribution width (RDW), and international normalization index (INR) as independent risk factors for ACLF patients. A simplified RSF model was developed based on these previous risk factors. The AUROCs for predicting 3-, 6-, and 12-month mortality were 0.916, 0.916, and 0.905 for the RSF model and 0.872, 0.866, and 0.848 for the Cox model in the model cohort, respectively. The Brier scores were 0.119, 0.119, and 0.128 for the RSF model and 0.138, 0.146, and 0.156 for the Cox model, respectively. The nonparametric comparison suggested that the RSF model was superior to the Cox model for predicting the prognosis of ACLF patients. CONCLUSIONS: The current study developed a novel online individual mortality risk predictive tool that could predict individual mortality risk predictive curves for individual patients. Additionally, the current online individual mortality risk predictive tool could further provide predicted mortality percentages and 95% confidence intervals at user-defined time points.

Relationship between optical coherence tomography retinal parameters and visual acuity in diabetic macular edema.

PURPOSE: To investigate the relationship between optical coherence tomography (OCT)-derived measurements of retinal morphology and visual acuity in patients with diabetic macular edema. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: A total of 67 consecutive patients (67 eyes) with diabetic macular edema (DME) who underwent Stratus OCT imaging (Carl Zeiss Meditec, Inc., Dublin, CA). METHODS: Best-corrected Snellen visual acuity was recorded for each patient. Raw exported Stratus OCT images for each patient were analyzed using custom software entitled "OCTOR," which allows the precise positioning of prespecified boundaries on individual B-scans. Thickness, volume, and intensity were calculated for neurosensory retina and subretinal fluid. In addition, photoreceptor outer segment (POS) thickness was quantified. MAIN OUTCOME MEASURES: Optical coherence tomography-derived measurements of retinal morphology and visual acuity. RESULTS: The Spearman coefficient values (r) of the correlation between OCTOR-derived measurements of central subfield thickness, intensity, subretinal fluid volume, and POS thickness and the logarithm of the minimum angle of resolution visual acuities were 0.3428 (P = 0.005), -0.2658 (P = 0.03), -0.2683 (P = 0.38), and -0.3703 (P = 0.002), respectively. Multivariate models with stepwise selection revealed a cumulative R(2) of 0.4305 in the total study population, with R(2) of 0.4999 and 0.7628 in the untreated and prior focal laser groups, respectively. CONCLUSIONS: Subanalysis and quantification of OCT features in eyes with DME seem to be of value. In particular, POS thickness seems to be an important predictor of function and visual acuity in patients with DME.

FibroScan Detection of Fatty Liver/Liver Fibrosis in 2266 Cases of Chronic Hepatitis B.

Background and Aims: FibroScan is used to determine liver stiffness and controlled attenuation parameter (referred to as CAP) scores in patients, including those with chronic hepatitis B (CHB). We used FibroScan to detect the incidence of fatty liver and fibrosis in CHB patients, and to assess the correlation of FibroScan measurements with blood chemistry tests. Methods: CHB patients enrolled in this study were divided independently for three separate analyses (of fibrosis, cirrhosis, and fatty liver) based on FibroScan results. Basic information, blood chemistry test results, liver fibrosis parameters, and FibroScan results were collected. T-tests and Pearson's analyses were used to analyze the correlations between FibroScan liver stiffness measurement/CAP values and liver function, blood fat, uric acid metabolite, fibrosis, and hepatitis B virus load. Results: A total of 2266 CHB patients were enrolled in the study and divided into three groups: non-significant and significant fibrosis; non-cirrhosis and early cirrhosis; and non-fatty and fatty liver. Spearman's statistical analyses showed that liver stiffness measurement or CAP values correlated with sex (r=0.137), age (r=0.119),glutamic-pyruvic transaminase (r=0.082), glutamic-oxaloacetic transaminase (r=-0.172), gamma-glutamyltransferase (r=0.225), albumin (r=0.150), globulin (r=-0.107), total bilirubin (r=-0.132), direct bilirubin (r=-0.145), white blood cell count (r=0.254), hemoglobin (r=0.205), platelets (r=0.206), total cholesterol (r=0.214), high density lipoprotein (r=-0.243), low density lipoprotein (r=0.255), apolipoprotein B (r=0.217), hyaluronic acid (r=-0.069), laminin (r=-0.188), procollagen type IV (r=-0.067)and hepatitis B viral DNA load (r=-0.216). Conclusions: FibroScan is a non-invasive device that can detect the occurrence of fatty liver or liver fibrosis in CHB patients.

[Clinical manifestations and gene analysis in one Chinese family with Best vitelliform macular dystrophy].

OBJECTIVE: To describe clinical phenotype in a Chinese family with Best vitelliform macular dystrophy (BVMD) and to identify the mutation of the VMD2 gene in this family. METHODS: It was a retrospective case analysis. Five patients (10 eyes) were diagnosed as BVMD by the fundus photography, EOG, fluorescein angiography (FFA) and optical coherence tomography (OCT). Their clinical data were analyzed retrospectively. Molecular genetic analysis was performed on DNA extracted from peripheral leucocytes of all patients and 2 unaffected family members. Exon 1 to 11 of the VMD2 gene were amplified by polymerase chain reaction for direct sequencing. RESULTS: The pedigree showed an autosomal dominant inheritance. Ten eyes from 5 patients were classified into Stage 0, II a, II b, III and IV with different clinical manifestations. Direct sequencing of all affected members revealed a T-->G transition at codon 301, producing Asp301Glu mutation of VMD2 gene. CONCLUSIONS: Asp301Glu mutation of the VMD2 gene is found in a Chinese family with BVMD. The phenotype of BVMD in this family belongs to geographic type. Molecular genetic approach may be useful for the proper diagnosis of BVMD.

Development and internal validation of a nine-lncRNA prognostic signature for prediction of overall survival in colorectal cancer patients.

BACKGROUND: Colorectal cancer remains a serious public health problem due to the poor prognosis. In the present study, we attempted to develop and validate a prognostic signature to predict the individual mortality risk in colorectal cancer patients. MATERIALS AND METHODS: The original study datasets were downloaded from The Cancer Genome Atlas database. The present study finally included 424 colorectal cancer patients with wholly gene expression information and overall survival information. RESULTS: A nine-lncRNA prognostic signature was built through univariate and multivariate Cox proportional regression model. Time-dependent receiver operating characteristic curves in model cohort demonstrated that the Harrell's concordance indexes of nine-lncRNA prognostic signature were 0.768 (95% CI [0.717-0.819]), 0.778 (95% CI [0.727-0.829]) and 0.870 (95% CI [0.819-0.921]) for 1-year, 3-year and 5-year overall survival respectively. In validation cohort, the Harrell's concordance indexes of nine-lncRNA prognostic signature were 0.761 (95% CI [0.710-0.812]), 0.801 (95% CI [0.750-0.852]) and 0.883 (95% CI [0.832-0.934]) for 1-year, 3-year and 5-year overall survival respectively. According to the median of nine-lncRNA prognostic signature score in model cohort, 424 CRC patients could be stratified into high risk group (n = 212) and low risk group (n = 212). Kaplan-Meier survival curves showed that the overall survival rate of high risk group was significantly lower than that of low risk group (P < 0.001). DISCUSSION: The present study developed and validated a nine-lncRNA prognostic signature for individual mortality risk assessment in colorectal cancer patients. This nine-lncRNA prognostic signature is helpful to evaluate the individual mortality risk and to improve the decision making of individualized treatments in colorectal cancer patients.

[Clinical features of Best vitelliform macular dystrophy].

OBJECTIVE: To investigate the clinical features of Best vitelliform macular dystrophy (BVMD) in Chinese patients. METHODS: Ten consecutive patients (20 eyes) were diagnosed as BVMD by the fundus photography, EOG, fluorescein angiography (FFA) and optical coherence tomography (OCT). Their clinical data were analyzed retrospectively. RESULTS: Of the twenty eyes from ten patients, three eyes from three patients (age range 9-18 years, mean 12.33+/-4.93 years) in Stage II, two eyes from two patients (age range 9-18, mean 13.50+/-6.36 years) in Stage IIa, four eyes from two patients (age range 11-29 years, mean 20.00+/-10.39 years) in Stage III and eleven from six patients (age range 9-44 years, mean 27.09+/-14.02 years) in Stage IV were found at their first presentation to our hospital. OCT scan showed the broadening of the outer-retina-choroid-complex signal with the retinal elevation in Stage II. The moderately reflective material which represents the vitelliform material may accumulate forming a conical mound that would elevate the retinal sensory layer in Stage IIa. In 'pseudohypopon' or atrophy phase there may be a large volume of serous retinal detachment. If a fibrous macular or foveal atrophy was seen in the fundus photograph, the thinning of the outer-retina-choroid-complex signal with serous retinal detachment may be shown by OCT. CONCLUSIONS: The present observation is a first study on the clinical findings of Chinese BVMD patients. It supports the hypothesis that the yellowish material is located under the RPE. Long term evaluation with more patients should be done to acknowledge more characteristics of BVMD in Chinese patients.

Nomogram for cirrhosis in patients with chronic hepatitis B: A simple self-assessed scale for individual risk of cirrhosis.

The aim of this retrospective study was to establish a simple self-assessed scale for individual risk of cirrhosis in patients with chronic hepatitis B. A total of 1808 consecutive patients were enrolled and analyzed. According to the results of multivariate logistic regression analysis, a simple nomogram was calculated for cirrhosis. The area under receiver operating characteristic curves (AUROCs) were calculated to compare the diagnostic accuracy of nomogram with aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on the four factors (FIB-4), and S index. The AUROCs of nomogram for cirrhosis were 0.807 (adjusted AUROC 0.876) in model group and 0.794 (adjusted AUROC0.866) in validation group. DeLong's test and Brier Score further demonstrated that nomogram was superior to APRI, FIB-4 and S index in both model group and validation group. The patients with nomogram <0.07 could be defined as low risk group with cirrhosis prevalence lower than 4.3% (17/397). The patients with nomogram >0.52 could be defined as high risk group with cirrhosis prevalence higher than 73.0% (119/163). In conclusion, as a self-assessed style, simple, non-invasive, economical, convenient, and repeatable scale, nomogram is suitable to serve as a massive health screening tool for cirrhosis in CHB patients and further external validation is needed.