Optical coherence tomography angiography for detection of microvascular changes in early diabetes: A systematic review and meta-analysis.

AIMS: To evaluate the effectiveness of optical coherence tomography angiography (OCTA) in detecting early intraocular microvascular changes in diabetic patients. MATERIALS AND METHODS: A systematic study search was performed on PubMed, Medline, Embase, and the Cochrane Library, ranging from January 2012 to March 2023. Controlled studies compared diabetes mellitus (DM) patients with non-diabetic retinopathy (NDR) or patients with mild non-proliferative diabetic retinopathy (mild NPDR) to healthy people. These studies included parameters of OCTA such as foveal avascular zone (FAZ), vessel density of superficial capillary plexus (VDscp), vessel density of deep capillary plexus (VDdcp), and peripapillary VD. The relevant effect model was used according to the heterogeneity, and the mean difference and 95% confidence intervals were calculated. RESULTS: A total of 18 studies with 2101 eyes were eventually included in this meta-analysis. Our results demonstrated that early alterations of VDscp, VDdcp, and peripapillary VD in NDR patients had a significant difference compared with healthy people by OCTA (VDscp: WMD = -1.34, 95% CI: -1.99 to -0.68, P < 0.0001. VDdcp: WMD = -2.00, 95% CI: -2.95 to -1.04, P < 0.0001. Peripapillary VD: WMD = -1.07, 95% CI: -1.70 to -0.43, P = 0.0010). However, there was no statistically significant difference in total FAZ between them (WMD = -0.00, 95% CI: -0.02-0.01, P = 0.84). In addition, for patients with mild NPDR, OCTA could illustrate prominent changes in VDscp, VDdcp, and total FAZ compared with healthy people (VDscp: WMD = -6.11, 95% CI: -9.90 to -2.32, P = 0.002. VDdcp: WMD = -4.26, 95% CI: -5.95 to -2.57, P < 0.00001. FAZ: WMD = 0.06, 95% CI: 0.01-0.11, P = 0.03). CONCLUSIONS: In diabetic patients with or without retinopathy, the parameters of OCTA such as VDscp, VDdcp, and peripapillary vessel density were demonstrated as potential biomarkers in monitoring the early alterations of retinal microangiopathy, while total FAZ may have no significant changes in diabetic patients without retinopathy.

Comparison of the efficiency of anti-VEGF drugs intravitreal injections treatment with or without retinal laser photocoagulation for macular edema secondary to retinal vein occlusion: A systematic review and meta-analysis.

Objective: To compare the efficiency of anti-VEGF drugs intravitreal injections(IVI) treatment with or without retinal laser photocoagulation(LPC) for macular edema(ME) secondary to retinal vein occlusion(RVO). Methods: The randomized controlled trials and retrospective studies including anti-VEGF drug IVI combined with retinal LPC and single IVI in the treatment of macular edema secondary to RVO were collected in PubMed, Medline, Embase, Cochrane Library, and Web of Science. We extracted the main outcome indicators including the best corrected visual acuity (BCVA), central macular thickness(CMT), the number of injections and the progress of retinal non-perfusion areas(NPAs) for systematic evaluation, to observe whether IVI + LPC could be more effective on the prognosis of RVO. We use Review Manager 5.4 statistical software to analyze the data Results: 527 articles were initially retrieved. We included 20 studies, with a total of 1387 patients who were divided into the combination(IVI + LPC) treatment group and the single IVI group. All the patients completed the ocular examination including BCVA, slit-lamp test, fundus examination and Optical Coherence Tomography(OCT) test before and after each treatment. There was no statistical difference between the combination treatment group and single IVI group on BCVA(WMD = 0.12,95%CI = -3.54-3.78,p = 0.95),CMT(WMD = -4.40,95%CI = -21.33-12.53,p = 0.61) and NPAs(WMD = 0.01,95%CI = -0.28-0.30,p = 0.94).However, the number of IVI was decreased significantly in the combination treatment group in BRVO patients, compared to that in the single IVI group(WMD = -0.69,95%CI = -1.18∼-0.21,p = 0.005). Conclusion: In the treatment of RVO patients with macular edema, the combination of IVI and retinal LPC neither improves BCVA nor reduces CMT significantly compared with the single IVI treatment. However, the combination treatment can decrease the number of intravitreal injections in patients with BRVO, while it is not observed in CRVO patients.

Iodixanol activation of mast cells: Implications in the pathogenesis of iodixanol-induced delayed cutaneous adverse reactions.

Iodinated contrast media (ICM) is widely used in radiological examination and interventional therapy. In the commonly used ICM, iodixanol is considered to be the safer one. However, compared with other ICMs, it has a higher incidence of delayed cutaneous adverse reactions. The underlying mechanisms are unclear. In this study, mice with positive allergic reactions were selected based on the mouse clinical allergy symptom score and skin and blood samples taken 1, 6, 24, 48, and 72 h after ICMs (6 g iodine/kg) injection for histological and blood analyses. ICMs-induced pseudo-allergic reactions were investigated through in vivo intravital vascular imaging and passive cutaneous anaphylaxis (PCA) not mediated by IgE and through, calcium imaging degranulation of mast cells (MCs), and western blot assays in vitro. Results shows iodixanol-induced systemic anaphylaxis caused severe extravasation of plasma proteins and degranulation of skin MCs, and increased levels of plasma histamine, cytokines and inflammatory chemokines. Mechanistically, iodixanol increases degranulation of MCs and promotes the synthesis of inflammatory factors by activating PLC-γ and PI3K-related pathways. Trigonelline inhibit iodixanol-induced MC-related pseudo-allergic reactions in vitro and in vivo. These results suggest that mice in the iodixanol group had a higher incidence of delayed cutaneous reactions, characterized by cytokine release over time and delayed cutaneous MC degranulation. Iodixanol's delayed cutaneous adverse reactions may be due to a delayed phase of MC-related pseudo-allergic reactions. Trigonelline revealed anti-allergic activity in iodixanol-induced MC-related pseudo-allergic reactions.

Identification of Inflammatory Response-Related Gene Signature Associated With Immune Status and Prognosis of Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is an exceedingly diverse disease, making prognostication difficult. Inflammatory responses in the tumor or the tumor microenvironment can alter prognosis in the process of the ongoing cross-talk between the host and the tumor. Nonetheless, Inflammatory response-related genes' prognostic significance in LUAD, on the other hand, has yet to be determined. Materials and Methods: The clinical data as well as the mRNA expression patterns of LUAD patients were obtained from a public dataset for this investigation. In the TCGA group, a multigene prognostic signature was built utilizing LASSO Cox analysis. Validation was executed on LUAD patients from the GEO cohort. The overall survival (OS) of low- and high-risk cohorts was compared utilizing the Kaplan-Meier analysis. The assessment of independent predictors of OS was carried out utilizing multivariate and univariate Cox analyses. The immune-associated pathway activity and immune cell infiltration score were computed utilizing single-sample gene set enrichment analysis. GO keywords and KEGG pathways were explored utilizing gene set enrichment analysis. Results: LASSO Cox regression analysis was employed to create an inflammatory response-related gene signature model. The high-risk cohort patients exhibited a considerably shorter OS as opposed to those in the low-risk cohort. The prognostic gene signature's predictive ability was demonstrated using receiver operating characteristic curve analysis. The risk score was found to be an independent predictor of OS using multivariate Cox analysis. The functional analysis illustrated that the immune status and cancer-related pathways for the two-risk cohorts were clearly different. The tumor stage and kind of immune infiltrate were found to be substantially linked with the risk score. Furthermore, the cancer cells' susceptibility to anti-tumor medication was substantially associated with the prognostic genes expression levels. Conclusion: In LUAD, a new signature made up of 8 inflammatory response-related genes may be utilized to forecast prognosis and influence immunological state. Inhibition of these genes could also be used as a treatment option.

ceRNA network development and tumor-infiltrating immune cell analysis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is among the primary causes of cancer deaths globally. Despite efforts to understand liver cancer, its high morbidity and mortality remain high. Herein, we constructed two nomograms based on competing endogenous RNA (ceRNA) networks and invading immune cells to describe the molecular mechanisms along with the clinical prognosis of HCC patients. RNA maps of tumors and normal samples were downloaded from The Cancer Genome Atlas database. HTseq counts and fragments per megapons per thousand bases were read from 421 samples, including 371 tumor samples and 50 normal samples. We established a ceRNA network based on differential gene expression in normal versus tumor subjects. CIBERSORT was employed to differentiate 22 immune cell types according to tumor transcriptomes. Kaplan-Meier along with Cox proportional hazard analyses were employed to determine the prognosis-linked factors. Nomograms were constructed based on prognostic immune cells and ceRNAs. We employed Receiver operating characteristic (ROC) and calibration curve analyses to estimate these nomogram. The difference analysis found 2028 messenger RNAs (mRNAs), 128 micro RNAs (miRNAs), and 136 long non-coding RNAs (lncRNAs) to be significantly differentially expressed in tumor samples relative to normal samples. We set up a ceRNA network containing 21 protein-coding mRNAs, 12 miRNAs, and 3 lncRNAs. In Kaplan-Meier analysis, 21 of the 36 ceRNAs were considered significant. Of the 22 cell types, resting dendritic cell levels were markedly different in tumor samples versus normal controls. Calibration and ROC curve analysis of the ceRNA network, as well as immune infiltration of tumor showed restful accuracy (3-year survival area under curve (AUC): 0.691, 5-year survival AUC: 0.700; 3-year survival AUC: 0.674, 5-year survival AUC: 0.694). Our data suggest that Tregs, CD4 T cells, mast cells, SNHG1, HMMR and hsa-miR-421 are associated with HCC based on ceRNA immune cells co-expression patterns. On the basis of ceRNA network modeling and immune cell infiltration analysis, our study offers an effective bioinformatics strategy for studying HCC molecular mechanisms and prognosis.

Multifocal Electroretinogram Can Detect the Abnormal Retinal Change in Early Stage of type2 DM Patients without Apparent Diabetic Retinopathy.

PURPOSE: To study retinal function defects in type 2 diabetic patients without clinically apparent retinopathy using a multifocal electroretinogram (mf-ERG). METHODS: Seventy-six eyes of thirty-eight type 2 diabetes mellitus(DM) patients without clinically apparent retinopathy and sixty-four normal eyes of thirty-two healthy control (HC) participants were examined using mf-ERG. RESULTS: Patients with type 2 DM without apparent diabetic retinopathy demonstrated an obvious implicit time delay of P1 in ring 1, ring 3, and ring 5 compared with healthy controls (t = 5.184, p ≤ 0.001; t = 8.077, p ≤ 0.001; t = 2.000, p = 0.047, respectively). The implicit time (IT) in ring 4 of N1wave was significantly delayed in the DM group (t = 2.327, p = 0.021). Compared with the HC group, the implicit time of the P1 and N1 waves in the temporal retina zone was significantly prolonged (t = 3.66, p ≤ 0.001; t = 2.187, p = 0.03, respectively). And the amplitude of P1 in the temporal retina decreased in the DM group, which had a significantly statistical difference with the healthy controls (t = -6.963, p ≤ 0.001). However, there were no differences in either the amplitude of the response or the implicit time of the nasal retina zone between DM and HC. The AUC of multiparameters of mf-ERG was higher in the diagnosis of DR patients. CONCLUSIONS: Patients with type 2 DM without clinically apparent retinopathy had a delayed implicit time of P1 wave in temporal regions of the postpole of the retina compared with HC subjects. It demonstrates that mf-ERG can detect the abnormal retinal change in the early stage of type2 DM patients without apparent diabetic retinopathy. Multiparameters of mf-ERG can improve the diagnostic efficacy of DR, and it may be a potential clinical biomarker for early diagnosis of DR.

miR­23b inhibits proliferation of SMMC­7721 cells by directly targeting IL­11.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer­associated mortality in the 21st century. microRNA (miR)­23b has been shown to be involved in the pathogenesis of many cancers, including breast and prostate cancer. However, the role of miR­23b in HCC remains unclear. The present study revealed a negative correlation between miR­23b expression in HCC tissues and progression of carcinomas. Compared to normal tissues, miR­23b expression was significantly downregulated in HCC tissues, whereas the expression of interleukin (IL)­11 and IL­11 receptor α (IL­11Rα) was significantly upregulated, indicating that miR­23b expression is negatively correlated with IL­11 and IL­11Rα expression. In addition, miR­23b inhibited proliferation and promoted apoptosis of SMMC­7721 cells. This effect was mediated by IL­11, which was found to be the direct target of miR­23b in this study. These results indicated that miR­23b regulates IL­11 and IL­11Rα expression, and might act as an anti­oncogenic agent in the progression of HCC by directly downregulating IL­11 expression.

Pirfenidone Inhibits Proliferation and Promotes Apoptosis of Hepatocellular Carcinoma Cells by Inhibiting the Wnt/ß-Catenin Signaling Pathway.

BACKGROUND Hepatocellular carcinoma (HCC) is the most important cause of cancer-related deaths worldwide. Pirfenidone is an orally available small molecule with therapeutic potential for fibrotic diseases. MATERIAL AND METHODS In this study, we analyzed the effects of different pirfenidone concentrations on the proliferation of HepG2 HCC cells using Cell Counting Kit-8 (CCK-8) and colony formation assays. Flow cytometry was performed to measure the apoptotic effects of pirfenidone on HepG2 cells. Western blot analysis was performed to detect the expression of ß-catenin and p-ß-catenin. RESULTS Pirfenidone inhibited proliferation and promoted HepG2 cell apoptosis. In addition, Western blot results indicated that pirfenidone suppressed b-catenin expression in HepG2 cells. To assess the mechanism, we treated HepG2 cells with pirfenidone, and pirfenidone plus the ß-catenin activator, SB-216763. The results revealed that SB-216763 accelerated proliferation and inhibited apoptosis in HepG2 cells treated with pirfenidone. Western blot results showed that SB-216763 upregulated ß-catenin expression in HepG2 cells treated with pirfenidone. CONCLUSIONS In conclusions, pirfenidone may be a potential drug for HCC treatment.