Retinal Microvascular Abnormalities Predict Clinical Outcomes in Patients with Heart Failure.

BACKGROUND: Narrower retinal arterioles and wider retinal venules have been associated with the incidence of heart failure (HF). However, whether they are predictive of the prognosis of heart failure (HF) is unclear. We aimed to explore the role of retinal vessel calibers in predicting long-term clinical outcomes of HF. METHODS: This is a prospective, single-center, observational study that surveyed patients in a tertiary referral hospital for the treatment of HF. Retinal vessel caliber was graded using retinal photography. The primary endpoint was the composite endpoint of HF rehospitalization and mortality at 12 months. RESULTS: There were 55 patients with chronic HF included in the final analysis. At 12 months, the cumulative incidence of the primary endpoint, HF rehospitalization, and mortality tended to be higher with the widening of the central retinal venular equivalent (CRVE) (p for non-linearity = 0.059) and was significantly increased when CRVE reached a cut-off value (283 µm) (p = 0.011) following adjustment for age, sex, etiology of HF, and diabetes. No association between the central retinal arteriolar equivalent (CRAE) and arteriolar-to-venular caliber ratio (AVR) was found with the clinical outcome in both univariable and multivariable Cox regression. CRAE, CRVE, and AVR had no relationship with the concentration of the N-terminal pro-B-type natriuretic peptide. In addition, CRVE was not associated with cardiac diastolic and systolic function. CONCLUSIONS: When the retinal venular caliber widens to a certain point, the composite incidence of HF rehospitalization and mortality significantly increase, suggesting retinal vessel caliber imaging may provide insight into the development of HF.

Application of iris fluorescein angiography in diabetic iridopathy and retinopathy in brown iris.

PURPOSE: This study aimed to evaluate the relationship between diabetic iridopathy (DI) and diabetic retinopathy (DR) and distinguish iris neovascular and physiological leakage using iris fluorescein angiography (IFA). METHODS: A total of 210 subjects were prospectively recruited in this study. Sixty normal subjects were divided equally into three groups (<40 years old, 40-59 years old, and 60-79 years old). One hundred fifty patients with diabetic mellitus (DM) were divided equally into five groups (no retinopathy, mild non proliferative DR (mildnPDR), moderate nPDR, severe nPDR, and PDR group). Normal subjects underwent IFA. Patients with DR underwent both IFA and ultrawide field fundus fluorescein angiography (uwFFA) at the same time. The leakage time and area were recorded and compared with each group. RESULTS: Fluorescein leakage occurred at the pupillary edge of patients that were 40-59 and 60-79 years old but not in those <40 years old. In the PDR group, the leakage time was earlier and the leakage area was larger than nPDR and patients with no retinopathy (p = 0.039 and p = 0.005, respectively). However, the leakage time and area were not significantly different between patients with no retinopathy and nPDR (p > 0.05). CONCLUSION: IFA examination can only assist in estimating the fundus severity of PDR patients, whereas the fundus changes of patients with no retinopathy and nPDR were not related to DI changes.Trial registration No.: ChiCTR1800018003.The date of registration: Aug 26th, 2018.

The effect of hemodialysis on ocular changes in patients with the end-stage renal disease.

Background: Numerous metabolic parameters can be changed during hemodialysis in the end-stage renal disease (ESRD) caused by systemic diseases, such as diabetes mellitus, hypertension. Some ocular parameters also can be variable due to the changes after hemodialysis. This study evaluates the effects of ocular parameters, including best-corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), retinal arteriolar caliber (RAC), retinal venular calibre (RVC), in ESRD patients following hemodialysis. Materials and methods: Two-hundred and two ESRD patients were recruited resulting in 404 eyes evaluations. All patients underwent hemodialysis in the Dialysis Unit of the Second Hospital of Tianjin Medical University. BCVA, CMT, IOP, SFCT, RAC and RVC were evaluated before and after hemodialysis. Systemic parameters were collected such as age, body weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), duration of hemodialysis, body weight changes, high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), very low density lipoprotein cholesterol (VLDLC), glycosylated hemoglobin (HbA1c). Results: The causes of ESRD patients included chronic glomerulonephritis (n = 65), diabetes mellitus (n = 60), hypertensive nephrosclerosis (n = 37), and other causes (n = 40). In our study, BCVA (p = .817), CMT (p = .252) and IOP (p = .978) did not significantly change after hemodialysis. SFCT significantly decreased from 254.29 ± 69.36 µm to 235.54 ± 659.90 µm (p = .002) following hemodialysis. SFCT changes were significantly correlated with SBP (p = .042) and body weight changes (p = .044). The RAC and RVC were dilated significantly (p = .033, p = .007). RVC changes were correlated with baseline DBP (p = .003), HDLC (p = .009), LDLC (p = .004) and changes in DBP (p = .037) and body weight (p = .001). Conclusion: Hemodialysis can affect various ocular parameters including SFCT, RAC and RVC, which changed significantly following hemodialysis. Whereas BCVA, IOP and CMT did not change after hemodialysis in ESRD patients. The systemic compensatory mechanisms of the changes in SBP, DBP, body weight following hemodialysis need further study.

The efficacy of conbercept or ranibizumab intravitreal injection combined with laser therapy for Coats' disease.

PURPOSE: The current treatment approaches for Coats' disease by intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents (ranibizumab or conbercept) combined with laser therapy were evaluated for the efficacy during the treatment. METHODS: The medical records of 28 patients diagnosed with Coats' disease followed by the treatment with intravitreal injection of anti-VEGF agents and laser therapies at Tianjin Medical University Eye Hospital and Hebei Eye Hospital during July 2012 and October 2017 were reviewed retrospectively. Clinical outcomes were recorded with a minimum follow-up of 6 months. The patients were divided into ranibizumab- and conbercept-treated groups, as well as based on age: pediatric and adult groups. RESULT: Twenty-eight patients were involved in this study. The average number of the injections was 2.82 ± 0.98. Laser photocoagulation was conducted in all patients, and the average number of lasers was 2.63 ± 0.74. The average follow-up period was 24.29 ± 9.85 months. Fourteen patients (50%) were stable, 12 (43%) patients were improved, and 2 patients (7%) showed recurred subretinal fluid and exudation. The final best corrected visual acuity (BCVA) increased markedly after intravitreal injection of ranibizumab or conbercept combined with laser therapy (p = 0.029, p = 0.009, respectively). The number of injections and lasers between conbercept and ranibizumab groups did not vary significantly (p = 0.160, p = 0.573, respectively). Nine patients (60%) in the ranibizumab-treated group and five (38%) in the conbercept-treated group reached a stable phase, and five (33%) and seven (54%) patients got the vision improved after treated with ranibizumab or conbercept, respectively. In pediatric and adult groups, the initial and final BCVA differed significantly (p = 0.03, p = 0.008, respectively). However, the injection number was remarkably different (p = 0.02), while the laser numbers did not have any markedly difference (p = 0.38). CONCLUSION: Intravitreal injection of ranibizumab or conbercept combined with laser therapy is an effective therapeutic option in Coats' disease. Moreover, the intravitreal injection of ranibizumab or conbercept had no significant adverse effects and appeared to offer visual improvement in Coats' disease.

Quantitative proteomics reveals that long non-coding RNA MALAT1 interacts with DBC1 to regulate p53 acetylation.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a broadly expressed lncRNA involved in many aspects of cellular processes. To further delineate the underlying molecular mechanism, we employed a high-throughput strategy to characterize the interacting proteins of MALAT1 by combining RNA pull-down, quantitative proteomics, bioinformatics, and experimental validation. Our approach identified 127 potential MALAT1-interacting proteins and established a highly connected MALAT1 interactome network consisting of 788 connections. Gene ontology annotation and network analysis showed that MALAT1 was highly involved in five biological processes: RNA processing; gene transcription; ribosomal proteins; protein degradation; and metabolism regulation. The interaction between MALAT1 and depleted in breast cancer 1 (DBC1) was validated using RNA pull-down and RNA immunoprecipitation. Further mechanistic studies reveal that MALAT1 binding competes with the interaction between sirtuin1 (SIRT1) and DBC1, which then releases SIRT1 and enhances its deacetylation activity. Consequently, the deacetylation of p53 reduces the transcription of a spectrum of its downstream target genes, promotes cell proliferation and inhibits cell apoptosis. Our results uncover a novel mechanism by which MALAT1 regulates the activity of p53 through the lncRNA-protein interaction.

Ectopic overexpression of filamin C scaffolds MEK1/2 and ERK1/2 to promote the progression of human hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) invasion and metastasis are mediated by a complicated signal transduction network and downstream cytoskeletal and adhesion molecules. In this study, a microarray-based analysis revealed a dramatic increase in filamin C (FLNC), which is commonly expressed in muscle rather than in liver cells, in the two metastatic HCC cell lines MHCC97L and HCCLM3. Clinicopathological studies showed that increased FLNC expression was associated with microvascular invasion and poor prognosis. Specific hypomethylation was identified within the FLNC promoter region in HCC cell lines and patient tumor samples, which might contribute to the ectopic overexpression of FLNC. FLNC downregulation inhibited cell migration and impaired cell proliferation and promoted apoptosis. Mechanistic studies suggested that FLNC interacts with mitogen-activated extracellular signal-regulated kinase 1/2 (MEK1/2) and extracellular signal-regulated kinase 1/2 (ERK1/2) and that FLNC downregulation inhibited MEK1/2 and ERK1/2 activation. Xenographic tumor transplantation experiments in nude mice further confirmed the role of FLNC in HCC progression and metastasis. Our results reveal a novel mechanism by which the cytoskeletal protein FLNC enhances the mitogen-activated protein kinase signaling pathway during tumorigenesis.

Aberrant expression of pim-3 promotes proliferation and migration of ovarian cancer cells.

Pim kinase-3(Pim-3), a member of serine/threonine protein kinases, has been implicated in multiple human cancers and involved in Myc-induced tumorigenesis. However, little is known regarding its expression and biological function in human ovarian cancer. In this study we showed that the clinical significance and biological functions of Pim-3 in ovarian cancer and found that higher Pim-3 mRNA level are detected in ovarian cancer tissues than those in normal ovarian tissues. There are significant correlations between higher Pim-3 expression levels with the FIGO stage, histopathological subtypes, and distant metastasis in ovarian cancer patients. Lentivirus-mediated gene overexpression of Pim-3 significantly promotes the proliferation and migration of SKOV3 cell lines. Furthermore, MACC1 and Pim-3 expression were significantly correlated in human ovarian cancer cells, and overexpression of Pim-3 in ovary cancer cells increased MACC1 mRNA and protein expression. The data indicate that Pim-3 acts as a putative oncogene in ovary cancer and could be a viable diagnostic and therapeutic target for ovarian cancer.

Long non-coding RNAs involved in gynecological cancer.

Long non-coding RNAs (lncRNAs) are defined as transcripts longer than 200 nucleotides with little or no protein-coding capacity. Previously, they were considered transcription byproducts without biological functions. Further studies have shown that lncRNAs are involved in multiple biological and pathological processes, including regulation of epigenetic, transcriptional, and posttranscriptional events. Long non-coding RNA expression patterns in various malignant tumors differ from those of benign tumors and normal tissue, and such alterations may promote or suppress tumorigenesis and cancer progression. The expression profiles of lncRNAs are abnormal in gynecological cancers, such as ovarian cancer, cervical cancer, and endometrial cancer, suggesting an important role for lncRNAs in tumorigenesis/progression of these cancers. Here, we summarized the research progress on identifying the biological functions of lncRNAs in tumorigenesis, progression, and metastasis in gynecological cancers. We provide references for exploring the clinical applications of lncRNAs as early diagnostic biomarkers or ideal therapeutic targets in gynecological cancers.