Conjunctival microvascular alteration in patients with coronary artery disease assessed using optical coherence tomographic angiography.

BACKGROUND: To quantify conjunctival microvascular characteristics obtained by optical coherence tomographic angiography (OCTA) and investigate their relationship with the presence and severity of coronary artery disease (CAD). METHODS: This cross-sectional study included 103 consecutive CAD patients confirmed by coronary angiography and 125 non-CAD controls. The temporal conjunctivas along the limbus of each participant were scanned using OCTA. Quantification of conjunctival microvasculature was performed by AngioTool software. The severity of the disease was evaluated using SYNTAX and Gensini scores. RESULTS: Compared to the controls, the CAD group exhibited significantly lower vessel area density (30.22 ± 3.34 vs. 26.70 ± 4.43 %, p < 0.001), lower vessel length density (6.39 ± 0.77 vs. 5.71 ± 0.89/m, p < 0.001), lower junction density (3.44 ± 0.56 vs. 3.05 ± 0.63/m, p < 0.001), and higher lacunarity (0.11 ± 0.03 vs. 0.14 ± 0.05, p < 0.001). Among all participants, lower vessel area density, lower vessel length density, lower junction density, and higher lacunarity were associated with greater odds of having CAD; the adjusted ORs (95 % confidence intervals) per one SD decrease were 2.71 (1.71, 4.29), 2.51(1.61, 3.90), 2.06 (1.39, 3.05), and 0.36 (0.23, 0.58), respectively. Among CAD patients, junction density was negatively associated with the Gensini score (r = -0.359, p = 0.037) and the Syntax score (r = -0.350, p = 0.042) in women but not in men (p > 0.05). CONCLUSIONS: Conjunctival microvascular characteristics were significantly associated with the presence of CAD. Junction density significantly associated with the severity of CAD among women patients.

Development of Vogt-Koyanagi-Harada disease-like uveitis during treatment by anti-programmed death-1 antibody: a case report.

BACKGROUND: Several immune checkpoint inhibitors (ICIs) have been linked to the occurrence of Vogt-Koyanagi-Harada disease (VKHD)-like uveitis. Among the ICIs, there has been no report of immune-related adverse events (irAEs) caused by a new programmed death protein-1(PD-1) monoclonal antibody (Toripalimab). CASE PRESENTATION: This paper presents a case of VKHD-like uveitis that arose following Toripalimab therapy for urothelial cancer of the bladder, and the patient experienced symptoms 10 days after the final dosage of 20 months of medication treatment. This patient with bladder uroepithelial carcinoma had severe binocular acute panuveitis with exudative retinal detachment after receiving Toripalimab therapy. Binocular VKHD-like uveitis was suggested as a diagnosis. Both eyes recovered after discontinuing immune checkpoint inhibitors and local and systemic corticosteroid treatment. CONCLUSIONS: This report suggests that VKHD-like uveitis can also occur in patients receiving novel PD-1 antibodies and the importance of paying attention to eye complications in patients receiving treatment over a long period.

Finite element analysis of biomechanical effects of percutaneous cement discoplasty in scoliosis.

OBJECTIVE: To investigate the effect of bone cement on the vertebral body and biomechanical properties in percutaneous cement discoplasty (PCD) for degenerative lumbar disc disease. METHODS: Three-dimensional reconstruction of L2 ~ L3 vertebral bodies was performed in a healthy volunteer, and the corresponding finite element model of the spine was established. Biomechanical analysis was performed on the changes in stress distribution in different groups of models by applying quantitative loads. RESULTS: Models with percutaneous discoplasty (PCD) showed improved stability under various stress conditions, and intervertebral foraminal heights were superior to models without discoplasty. CONCLUSION: Cement discoplasty can improve the stability of the vertebral body to a certain extent and restore a certain height of the intervertebral foramen, which has a good development prospect and potential.

A hybrid forecasting approach for China's national carbon emission allowance prices with balanced accuracy and interpretability.

A significant milestone in China's carbon market was reached with the official launch and operation of the National Carbon Emission Trading Market. The accurate prediction of the carbon price in this market is crucial for the government to formulate scientific policies regarding the carbon market and for companies to participate effectively. Nevertheless, it remains challenging to accurately predict price fluctuations in the carbon market because of the volatility and instability caused by several complex factors. This paper proposes a new carbon price forecasting framework that considers the potential factors influencing national carbon prices, including data decomposition and reconstruction techniques, feature selection techniques, machine learning forecasting techniques for intelligent optimisation, and research on model interpretability. This comprehensive framework aims to improve the accuracy and understandability of carbon price projections to respond better to the complexity and uncertainty of carbon markets. The results indicate that (1) the hybrid forecasting framework is highly accurate in forecasting national carbon market prices and far superior to other comparative models; (2) the factors driving national carbon prices vary according to the time scale. High-frequency series are sensitive to short-term economic and energy market indicators. Medium- and low-frequency series are more susceptible to financial markets and long-term economic conditions than high-frequency series. This study provides insights into the factors affecting China's national carbon market price and serves as a reference for companies and governments to develop carbon price forecasting tools.

CD44 loss of function sensitizes AML cells to the BCL-2 inhibitor venetoclax by decreasing CXCL12-driven survival cues.

Acute myeloid leukemia (AML) has a poor prognosis under the current standard of care. In recent years, venetoclax, a BCL-2 inhibitor, was approved to treat patients who are ineligible for intensive induction chemotherapy. However, complete remission rates with venetoclax-based therapies are hampered by minimal residual disease (MRD) in a proportion of patients, leading to relapse. MRD is a result of leukemic stem cells being retained in bone marrow protective environments; activation of the CXCL12-CXCR4 pathway was shown to be relevant to this process. An important role is also played by cell adhesion molecules such as CD44, which has been shown to be crucial for the development of AML. Here we show that CD44 is involved in CXCL12 promotion of resistance to venetoclax-induced apoptosis in human AML cell lines and AML patient samples, which could be abrogated by CD44 knock down, knockout, or blocking with an anti-CD44 antibody. Split-Venus bimolecular fluorescence complementation showed that CD44 and CXCR4 physically associate at the cell membrane upon CXCL12 induction. In the venetoclax-resistant OCI-AML3 cell line, CXCL12 promoted an increase in the proportion of cells expressing high levels of embryonic stem cell core transcription factors (ESC-TFs: Sox2, Oct4, Nanog) abrogated by CD44 knockdown. This ESC-TF-expressing subpopulation which could be selected by venetoclax treatment, exhibited a basally enhanced resistance to apoptosis and expressed higher levels of CD44. Finally, we developed a novel AML xenograft model in zebrafish, which showed that CD44 knockout sensitizes OCI-AML3 cells to venetoclax treatment in vivo. Our study shows that CD44 is a potential molecular target for sensitizing AML cells to venetoclax-based therapies.

A nomogram for predicting residual low back pain after percutaneous kyphoplasty in osteoporotic vertebral compression fractures.

To establish a risk prediction model for residual low back pain after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures. We used retrospective data for model construction and evaluated the model using internal validation and temporal external validation and finally concluded that the model had good predictive performance. INTRODUCTION: The cause of residual low back pain in patients with osteoporotic vertebral compression fractures (OVCFs) after PKP remains highly controversial, and our goal was to investigate the most likely cause and to develop a novel nomogram for the prediction of residual low back pain and to evaluate the predictive performance of the model. METHODS: The clinical data of 281 patients with OVCFs who underwent PKP at our hospital from July 2019 to July 2020 were reviewed. The optimal logistic regression model was determined by lasso regression for multivariate analysis, thus constructing a nomogram. Bootstrap was used to perfomance the internal validation; receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to assess the predictive performance and clinical utility of the model, respectively. Temporal external validation of the model was also performed using retrospective data from 126 patients who underwent PKP at our hospital from January 2021 to October 2021. RESULTS: Lasso regression cross-validation showed that the variables with non-zero coefficients were the number of surgical vertebrae, preoperative bone mineral density (pre-BMD), smoking history, thoracolumbar fascia injury (TLFI), intraoperative facet joint injury (FJI), and postoperative incomplete cementing of the fracture line (ICFL). The above factors were included in the multivariate analysis and showed that the pre-BMD, smoking history, TLFI, FJI, and ICFL were independent risk factors for residual low back pain (P < 0.05). The ROC and calibration curve of the original model and temporal external validation indicated a good predictive power of the model. The DCA curve suggested that the model has good clinical practicability. CONCLUSION: The risk prediction model has good predictive performance and clinical practicability, which can provide a certain basis for clinical decision-making in patients with OVCFs.

Characteristics of phenotypic antibiotic resistance of Helicobacter pylori and its correlation with genotypic antibiotic resistance: A retrospective study in Ningxia.

BACKGROUND: Geographic differences exist in the antibiotic resistance patterns of Helicobacter pylori. Personalized treatment regimens based on local or individual resistance data are essential. We evaluated the current status of H. pylori resistance in Ningxia, analyzed resistance-related factors, and assessed the concordance of phenotypic and genotypic resistance. METHODS: Strains were isolated from the gastric mucosa of patients infected with H. pylori in Ningxia and relevant clinical information was collected. Phenotypic antibiotic susceptibility assays (Kirby-Bauer disk diffusion) and antibiotic resistance gene detection (Sanger sequencing) were performed. RESULTS: We isolated 1955 H. pylori strains. The resistance rates of H. pylori to amoxicillin, levofloxacin, clarithromycin, and metronidazole were 0.9%, 42.4%, 40.4%, and 94.2%, respectively. Only five tetracycline-resistant and one furazolidone-resistant strain were identified. Overall, 3.3% of the strains were sensitive to all six antibiotics. Multidrug-resistant strains accounted for 22.9%, of which less than 20% were from Wuzhong. Strains isolated from women and patients with nonulcerative disease had higher rates of resistance to levofloxacin and clarithromycin. Higher rates of resistance to metronidazole, levofloxacin, and clarithromycin were observed in the older age group than in the younger age group. The kappa coefficients of phenotypic resistance and genotypic resistance for levofloxacin and clarithromycin were 0.830 and 0.809, respectively, whereas the remaining antibiotics showed poor agreement. CONCLUSION: H. pylori antibiotic resistance is severe in Ningxia. Therefore, furazolidone, amoxicillin, and tetracycline are better choices for the empirical therapy of H. pylori infection in this region. Host sex, age, and the presence of ulcerative diseases may affect antibiotic resistance of the bacteria. Personalized therapy based on genetic testing for levofloxacin and clarithromycin resistance may be a future direction for the eradication therapy of H. pylori infection in Ningxia.

PREDICTIVE ROLES OF QUANTITATIVE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES IN PROGNOSIS OF MYOPIC CHOROIDAL NEOVASCULARIZATION.

PURPOSE: To explore the predictive roles of the morphologic features of neovascularization in the prognosis of myopic choroidal neovascularization. METHODS: In this retrospective case series study, quantitative morphologic features of neovascularization were obtained from the optical coherence tomography angiography images. According to the number of anti-vascular endothelial growth factor injections administered within 1 year, the eyes were classified into a stable group (≤2 injections) or an unstable group (>2 injections). Best-corrected visual acuity was recorded before the treatment and at the 1-year follow-up. RESULTS: Overall, 50 eyes with treatment-naive myopic choroidal neovascularization were included; 26 in the stable group and 24 in the unstable group. Multivariate analysis showed that the eyes in the unstable group were associated with a larger lesion area (odds ratio = 2.596, P = 0.012), higher junction density (odds ratio = 1.611, P = 0.014), and higher end point density (odds ratio = 1.435, P = 0.023).The area under the receiver operating characteristic curve of the multivariate model was 0.865, with 91.7% sensitivity and 65.4% specificity. The final best-corrected visual acuity was significantly correlated with the lesion area (ß = 0.152, P = 0.032) after adjusted for age, sex, and baseline best-corrected visual acuity. CONCLUSION: Lesions with larger areas and higher end point and junction densities tended to have more frequent anti-vascular endothelial growth factor injections and worse visual outcomes in eyes with myopic choroidal neovascularization.

Acute and subacute intraocular pressure and macular microvascular structure changes after intravitreal ranibizumab injection in eyes with branch retinal vein occlusion.

PURPOSE: To investigate early changes in the intraocular pressure (IOP) and macular microvascular structure in eyes with branch retinal vein occlusion (BRVO) treated with intravitreal Ranibizumab injection. METHODS: This study enrolled 30 patients (one eye per patient) who received intravitreal injections (IVI) of ranibizumab for macular edema secondary to BRVO. IOP were measured before, 30 min (min) and 1 month following IVI. Changes in macular microvascular structure were examined via assessment of foveal avascular zone (FAZ) parameters, vascular density (VD) of superficial vascular complex (SVC), and deep vascular complex (DVC) in whole macula, central fovea and parafovea area which were measured automatically by optical coherence tomography angiography (OCTA) on the same time as IOP examinations. Paired t test and Wilcoxon test were used to compare pre- and post-injection values. The correlation between IOP and OCTA findings was assessed. RESULTS: IOP Measurements at 30 min post-IVI (17.91 ± 3.36 mmHg) increased significantly from baseline (15.07 ± 2.58 mmHg, p < 0.001), then became similar with baseline after 1 month (15.00 ± 3.16 mmHg, p = 0.925). 30 min past the injection, the parameters of VD of the SCP significantly decreased in comparison to baseline, then became similar with baseline after one month, while there were no significant changes in other OCTA parameters, including parameters of VD of the DCP and the FAZ. At 1 month after IVI, in comparison to baseline, no significant changes were observed in all of the OCTA parameters (P > 0.05). There were no significant correlations between IOP and OCTA findings no matter 30 min or 1 month post-IVI (P > 0.05). CONCLUSIONS: Transient IOP elevation and decreased superficial macular capillary perfusion density were detected 30 min post-IVI, however, no potential continual macular microvascular damage was suspected.

On-DNA Alkyne Iodination and Acetylenic Coupling as a Useful Tool for DEL Synthesis.

1-Iodoalkynes and 1,3-diynes are versatile chemical intermediates and pharmaceutically valuable ingredients. In this study, copper mediated on-DNA alkyne iodination and Cadiot-Chodkiewicz coupling are developed for the first time. This generates diverse, systematic, and unprecedented topographic structural features, which could be invaluable as molecular recognition agents for drug discovery in DEL screening.

PREDICTING LESION SHRINKAGE IN EYES WITH MYOPIC CHOROIDAL NEOVASCULARIZATION FROM FEATURES ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To identify baseline morphological predictors of lesion shrinkage in eyes with myopic choroidal neovascularization (mCNV) treated with anti-vascular endothelial growth factor. METHODS: This retrospective study included 46 eyes (41 consecutive patients) with active mCNV receiving anti-vascular endothelial growth factor treatment. Optical coherence tomography angiography was performed at baseline and 1 year after treatment. Quantitative features were obtained from optical coherence tomography angiography images using AngioTool software. Eyes were classified as "high shrinkage" or "low shrinkage" according to the median relative change in lesion area. Baseline quantitative morphological features associated with mCNV shrinkage were identified in univariate and multivariate analyses. RESULTS: The mCNV area was significantly smaller after 1 year ( P = 0.013), with a median relative change of -16.5%. The relative change in mCNV area was -48.3% in high-shrinkage eyes (n = 23) and -5.2% in low-shrinkage eyes (n = 23). High-shrinkage eyes had a smaller mCNV area ( P = 0.013), shorter total vessel length ( P = 0.023), and higher end point density ( P < 0.001). Multivariate analysis showed significant associations of high shrinkage with end point density (ß = -0.037, P = 0.043) and previous anti-vascular endothelial growth factor treatment (ß = 0.216, P = 0.029). CONCLUSION: Morphological features of neovascularization detected by optical coherence tomography angiography can predict lesion shrinkage in eyes with mCNV receiving anti-vascular endothelial growth factor therapy. Higher end point density contributed to shrinkage, particularly of treatment-naive lesions.

CD44 engagement enhances acute myeloid leukemia cell adhesion to the bone marrow microenvironment by increasing VLA-4 avidity.

Adhesive properties of leukemia cells shape the degree of organ infiltration and the extent of leukocytosis. CD44 and the integrin VLA-4, a CD49d/CD29 heterodimer, are important factors of progenitor cell adhesion in bone marrow (BM). Here, we report their cooperation in acute myeloid leukemia (AML) by a novel non-classical CD44-mediated way of inside-out VLA-4 activation. In primary AML BM samples from patients and the OCI-AML3 cell line, CD44 engagement by hyaluronan induced inside-out activation of VLA-4 resulting in enhanced leukemia cell adhesion on VCAM-1. This was independent from VLA-4 affinity regulation but based on ligand-induced integrin clustering on the cell surface. CD44-induced VLA-4 activation could be inhibited by the Src family kinase inhibitor PP2 and the multikinase inhibitor midostaurin. In further consequence, the increased adhesion on VCAM-1 allowed AML cells to strongly bind stromal cells. Thereby VLA-4/VCAM-1 interaction promoted activation of Akt, MAPK, NF-kB and mTOR signaling and decreased AML cell apoptosis. Collectively, our investigations provide a mechanistic description of an unusual CD44 function in regulating VLA-4 avidity in AML, supporting AML cell retention in the supportive BM microenvironment.

Early neurovascular changes in the retina in preclinical diabetic retinopathy and its relation with blood glucose.

BACKGROUND: To investigate the changes in retinal nerve fiber layer thickness and macular blood flow density during the preclinical stage of diabetic retinopathy and their relationship with blood glucose. METHODS: In this cross-sectional study, 97 diabetic patients (total of 188 eyes; 144 eyes in no diabetic retinopathy group, 44 eyes in mild diabetic non-proliferative retinopathy group) and 35 healthy people (70 eyes) were enrolled, All the subjects were divided into different groups based on their HbA1c levels, and they underwent optical coherence tomography angiography. We compared the optical coherence tomography angiography parameters and retinal nerve fiber layer thickness among the different glucose groups. RESULTS: The parafoveal vessel density and the temporal retinal nerve fiber layer thickness were lower (p < 0.05) in the diabetic group than in the normal group. The diabetic group showed a higher acircularity index than the normal group. The normal group had the highest vessel density and the lowest acircularity index, followed by the no-diabetic retinopathy group and the mild non-proliferative retinopathy group, (p < 0.001). Foveal vascular density and parafoveal vessel density decreased with an increase in HbA1c. There was a negative correlation between parafoveal vessel density in the deep retinal vascular layer and fasting blood glucose (p < 0.01). The temporal retinal nerve fiber layer thickness decreased across the HbA1c level groups, and was positively correlated with the parafoveal vessel density in the superficial retinal vascular layer (p < 0.05). CONCLUSIONS: This study shows that retinal microvasculopathy and neuropathy can be present in the absence of retinopathy. The vessel density of the deep retinal vascular layer was negatively correlated with fasting blood glucose, and the temporal retinal nerve fiber layer thickness was positively correlated with the vessel density of the superficial retinal vascular layer. These indicators are helpful for endocrinologists and ophthalmologists in detecting early diabetic retinal pathological lesions.

Microenvironment-induced CD44v6 promotes early disease progression in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) outgrowth depends on signals from the microenvironment. We have previously found that in vitro reconstitution of this microenvironment induces specific variant isoforms of the adhesion molecule CD44, which confer human CLL with high affinity to hyaluronan (HA). Here, we determined the in vivo contribution of standard CD44 and its variants to leukemic B-cell homing and proliferation in Tcl1 transgenic mice with a B-cell-specific CD44 deficiency. In these mice, leukemia onset was delayed and leukemic infiltration of spleen, liver, and lungs, but not of bone marrow, was decreased. Competitive transplantation revealed that CLL homing to spleen and bone marrow required functional CD44. Notably, enrichment of CD44v6 variants particularly in spleen enhanced CLL engraftment and proliferation, along with increased HA binding. We recapitulated CD44v6 induction in the human disease and revealed the involvement of MAPK and NF-κB signaling upon CD40 ligand and B-cell receptor stimulation by in vitro inhibition experiments and chromatin immunoprecipitation assays. The investigation of downstream signaling after CD44v6-HA engagement uncovered the activation of extracellular signal-regulated kinase and p65. Consequently, anti-CD44v6 treatment reduced leukemic cell proliferation in vitro in human and mouse, confirming the general nature of the findings. In summary, we propose a CD44-NF-κB-CD44v6 circuit in CLL, allowing tumor cells to gain HA binding capacity and supporting their proliferation.

Combination of Ranibizumab with macular laser for macular edema secondary to branch retinal vein occlusion: one-year results from a randomized controlled double-blind trial.

BACKGROUND: It is not clear whether macular laser combined with anti-vascular endothelial growth factor (VEGF) can reduce the number of anti-VEGF injections in the treatment of macular edema (ME) secondary to branch retinal vein occlusion (BRVO). Our study aimed to investigate the effects of intravitreal ranibizumab with or without macular laser for ME secondary to BRVO and its associated number of anti-VEGF injections. METHODS: This is a prospective, randomized, double-blind, monocentric trial.80 patients were enrolled and 64 patients fulfilled the study requirements. All patients received a minimum of 3 initial monthly ranibizumab injections, pro re nata (PRN) dosing thereafter VA and CRT stabilization criteria-driven PRN treatment. Laser was given 7 days after third ranibizumab injection in ranibizumab with laser group. The follow-up time of this study was 1 year. Best corrected visual acuity (BCVA) improvement, central retinal thickness (CRT) reduction and number of injections of patients were compared between two groups. T-test, non-parametric Wilcoxon test and chis-square tests were adopted for between-group comparisons. RESULTS: Thirty patients received intravitreal ranibizumab 0.5 mg alone and 34 patients received intravitreal ranibizumab 0.5 mg with macular laser. At 52 week, BCVA increased significantly and CRT decreased significantly in both groups (P < 0.001). However, there was no significant difference in BCVA improvement with baseline BCVA adjusted (p = 0.5226), and in the CRT reduction (P = 0.4552) between two groups after 52 weeks. There was also no significant difference in the number of injections between the two groups. (P = 0.0756). There was also no significant difference between ischemic and non-ischemic groups in BCVA improvement, CRT reduction and number of injections (P > 0.05). CONCLUSIONS: Our study suggests that ranibizumab combined with macular laser is effective in the treatment of ME secondary to BRVO after 1 year of treatment with 3 + PRN regimen. However, combination of macular grid photocoagulation showed no beneficial anatomical or functional effect during follow-up period, nor did it reduce the number of ranibizumab injections, either in ischemic group or non-ischemic group. We suggest that there is no need to combine macular grid photocoagulation in the treatment of ME secondary to BRVO in the future. TRIAL REGISTRATION: Clinical Trials NCT03054766. https://register.clinicaltrials.gov.Prospectively registered.

Identification of gene coexpression modules, hub genes, and pathways related to spinal cord injury using integrated bioinformatics methods.

Spinal cord injury (SCI) is characterized by dramatic neurons loss and axonal regeneration suppression. The underlying mechanism associated with SCI-induced immune suppression is still unclear. Weighted gene coexpression network analysis (WGCNA) is now widely applied for the identification of the coexpressed modules, hub genes, and pathways associated with clinic traits of diseases. We performed this study to identify hub genes associated with SCI development. Gene Expression Omnibus (GEO) data sets GSE45006 and GSE20907 were downloaded and the significant correlativity and connectivity between them were detected using WGCNA. Three significant consensus modules, including 567 eigengenes, were identified from the master GSE45006 data following the preconditions of approximate scale-free topology for WGCNA. Further bioinformatics analysis showed these eigengenes were involved in inflammatory and immune responses in SCI. Three hub genes Rac2, Itgb2, and Tyrobp and one pathway "natural killer cell-mediated cytotoxicity" were identified following short time-series expression miner, protein-protein interaction network, and functional enrichment analysis. Gradually upregulated expression patterns of Rac2, Itgb2, and Tyrobp genes at 0, 3, 7, and 14 days after SCI were confirmed based on GSE45006 and GSE20907 data set. Finally, we found that Rac2, Itgb2, and Tyrobp genes might take crucial roles in SCI development through the "natural killer cell-mediated cytotoxicity" pathway.

Mycobacterium marseillense Infection in Human Skin, China, 2018.

We describe a case of facial skin infection and sinusitis caused by Mycobacterium marseillense in an immunocompetent woman in China in 2018. The infection was cleared with clarithromycin, moxifloxacin, and amikacin. Antimicrobial drug treatments could not be predicted by genetic analyses; further genetic characterization would be required to do so.

Therapeutic effects of ranibizumab in patients with polypoidal choroidal vasculopathy.

BACKGROUND: There is no consensus on the optimal initial treatment for polypoidal choroidal vasculopathy (PCV). Our study aimed to report the efficacy of repeated injections of intravitreal ranibizumab with or without photodynamic therapy for the treatment of PCV and to determine the possible factors predictive of visual outcomes. METHODS: The results of the initial treatment of 40 patients with PCV with 3 monthly injections of ranibizumab were retrospectively reviewed. We compared the results in terms of the best corrected visual acuity (BCVA), the central retinal thickness (CRT), the number of injections, the regression rates of polyps and the rates of the reduction of subretinal fluid. RESULTS: At the 3-month follow-up, the mean BCVA was significantly increased by 7.3 ± 12.4 letters compared to baseline (p < 0.01). At the 12-month follow-up, the mean BCVA was increased by 3.4 ± 15.4 letters compared to baseline, and there was no significant difference (p > 0.05). The mean CRT at the 12-month follow-up was 593.58 ± 243.64 µm, with an average decrease of 101.55 ± 256.07 µm compared to baseline (p < 0.01). Fifteen eyes (18.8%) showed the complete regression of polyps, and 22 eyes (27.5%) showed a reduction in polyps. The baseline VA, the reduction in subretinal fluids and the greatest lesion diameter were significant independent factors that were predictive of improved VA at the final follow-up. CONCLUSIONS: Three monthly injections of ranibizumab as an initial treatment could significantly improve VA in PCV patients in the short term. At 12 months postinjection, ranibizumab treatment could stabilize VA in most PCV patients. The baseline VA, the reduction in subretinal fluids and the greatest lesion diameter were predictive factors for the relative improvement of VA at the final follow-up.

Intravitreal Dexamethasone Implant versus Intravitreal Ranibizumab for the Treatment of Macular Edema Secondary to Retinal Vein Occlusion in a Chinese Population.

BACKGROUND: The aim of this work was to compare the efficacy of intravitreal dexamethasone implant (Ozurdex) and intravitreal ranibizumab (Lucentis) in the treatment of macular edema (ME) caused by retinal vein occlusion (RVO). METHODS: Thirty-two ME cases treated with Ozurdex and 32 ME cases treated with ranibizumab were enrolled, with 26 central (C)RVO and 6 branch (B)RVO subjects in each group. We compared the results of best-corrected visual acuity (BCVA), central retinal thickness, number of injections, and intraocular pressure (IOP) at 1, 2, 3, and 6 months after injection. RESULTS: BCVA in both groups at each follow-up were significantly increased compared to baseline with no statistical difference between the groups. Ozurdex and ranibizumab successfully reduced CMT at each follow-up. Both CRVO and BRVO patients had significant between-group differences in the mean number of injections. Among the CRVO patients, IOP in the Ozurdex group was significantly increased compared to baseline and the ranibizumab group at 1, 2, and 3 months postinjection. CONCLUSIONS: Intravitreal injection of Ozurdex and ranibizumab can effectively control ME secondary to RVO and increase a patient's BCVA. The advantages of Ozurdex are fewer injections and longer efficacy, while the advantages of ranibizumab include fewer side effects.

A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing.

Adult cancers may derive from stem or early progenitor cells. Epigenetic modulation of gene expression is essential for normal function of these early cells but is highly abnormal in cancers, which often show aberrant promoter CpG island hypermethylation and transcriptional silencing of tumor suppressor genes and pro-differentiation factors. We find that for such genes, both normal and malignant embryonic cells generally lack the hypermethylation of DNA found in adult cancers. In embryonic stem cells, these genes are held in a 'transcription-ready' state mediated by a 'bivalent' promoter chromatin pattern consisting of the repressive mark, histone H3 methylated at Lys27 (H3K27) by Polycomb group proteins, plus the active mark, methylated H3K4. However, embryonic carcinoma cells add two key repressive marks, dimethylated H3K9 and trimethylated H3K9, both associated with DNA hypermethylation in adult cancers. We hypothesize that cell chromatin patterns and transient silencing of these important regulatory genes in stem or progenitor cells may leave these genes vulnerable to aberrant DNA hypermethylation and heritable gene silencing during tumor initiation and progression.