Machine learning and optical coherence tomography-derived radiomics analysis to predict persistent diabetic macular edema in patients undergoing anti-VEGF intravitreal therapy.

BACKGROUND: Diabetic macular edema (DME) is a leading cause of vision loss in patients with diabetes. This study aimed to develop and evaluate an OCT-omics prediction model for assessing anti-vascular endothelial growth factor (VEGF) treatment response in patients with DME. METHODS: A retrospective analysis of 113 eyes from 82 patients with DME was conducted. Comprehensive feature engineering was applied to clinical and optical coherence tomography (OCT) data. Logistic regression, support vector machine (SVM), and backpropagation neural network (BPNN) classifiers were trained using a training set of 79 eyes, and evaluated on a test set of 34 eyes. Clinical implications of the OCT-omics prediction model were assessed by decision curve analysis. Performance metrics (sensitivity, specificity, F1 score, and AUC) were calculated. RESULTS: The logistic, SVM, and BPNN classifiers demonstrated robust discriminative abilities in both the training and test sets. In the training set, the logistic classifier achieved a sensitivity of 0.904, specificity of 0.741, F1 score of 0.887, and AUC of 0.910. The SVM classifier showed a sensitivity of 0.923, specificity of 0.667, F1 score of 0.881, and AUC of 0.897. The BPNN classifier exhibited a sensitivity of 0.962, specificity of 0.926, F1 score of 0.962, and AUC of 0.982. Similar discriminative capabilities were maintained in the test set. The OCT-omics scores were significantly higher in the non-persistent DME group than in the persistent DME group (p < 0.001). OCT-omics scores were also positively correlated with the rate of decline in central subfield thickness after treatment (Pearson's R = 0.44, p < 0.001). CONCLUSION: The developed OCT-omics model accurately assesses anti-VEGF treatment response in DME patients. The model's robust performance and clinical implications highlight its utility as a non-invasive tool for personalized treatment prediction and retinal pathology assessment.

Deep learning-based fundus image analysis for cardiovascular disease: a review.

It is well established that the retina provides insights beyond the eye. Through observation of retinal microvascular changes, studies have shown that the retina contains information related to cardiovascular disease. Despite the tremendous efforts toward reducing the effects of cardiovascular diseases, they remain a global challenge and a significant public health concern. Conventionally, predicting the risk of cardiovascular disease involves the assessment of preclinical features, risk factors, or biomarkers. However, they are associated with cost implications, and tests to acquire predictive parameters are invasive. Artificial intelligence systems, particularly deep learning (DL) methods applied to fundus images have been generating significant interest as an adjunct assessment tool with the potential of enhancing efforts to prevent cardiovascular disease mortality. Risk factors such as age, gender, smoking status, hypertension, and diabetes can be predicted from fundus images using DL applications with comparable performance to human beings. A clinical change to incorporate DL systems for the analysis of fundus images as an equally good test over more expensive and invasive procedures may require conducting prospective clinical trials to mitigate all the possible ethical challenges and medicolegal implications. This review presents current evidence regarding the use of DL applications on fundus images to predict cardiovascular disease.

Emodin reverses resistance to gemcitabine in pancreatic cancer by suppressing stemness through regulation of the epithelial­mesenchymal transition.

The present study aimed to explore the effects and underlying mechanisms of emodin (Emo) on gemcitabine (GEM)-resistant pancreatic cancer. GEM-resistant SW1990 cells (SW1990/GZ) were established by successively doubling the concentration of GEM. Cell viability was measured using the CCK-8 assay and flow cytometry was used to measure cell apoptosis. Cell migration was assessed using a Transwell assay. Sphere and colony-formation assays were used to evaluate cell self-renewal. The expression levels of epithelial-mesenchymal transition (EMT) and stem cell biomarkers were determined using western blotting. Snail family transcriptional repressor 1 gene (Snail) was overexpressed by transfecting cells with pcDNA3.1-Snail plasmids. A xenograft model was established in nude mice by using SW1990/GZ and Snail-overexpressing SW1990/GZ cells. Proliferation, migration, self-renewal and EMT progression of GEM-treated SW1990/GZ cells were significantly suppressed in vitro by Emo treatment, whereas the overexpression of Snail abolished the aforementioned effects. In in vivo, the antitumor activity of GEM and the inhibitory effect of GEM against EMT progression and stem-like characteristics were enhanced by treatment with Emo, whilst overexpression of Snail reversed these effects. In conclusion, Emo reversed GEM resistance in pancreatic cancer by suppressing stemness and regulating EMT progression.

Positive circumferential resection margin in locally advanced esophageal cancer: an updated systematic review and meta-analysis.

BACKGROUND: The impact of positive circumferential resection margin on prognosis in esophageal cancer is under controversy. Previous systematic reviews and meta-analyses had limitations. This updated systematic review and meta-analysis aimed to assess the prognostic impact of positive circumferential resection margin in esophageal cancer.PubMed and Web of Science were searched for studies investigating the association between circumferential resection margin status and prognosis in esophageal cancer. Study population were focused on T3 and/or T4a patients. Study selection was based on availability of survival information (Kaplan-Meier curves and adjusted analysis). Random-effects models were used to summarize hazard ratios for overall survival and disease-free survival.According to College of American Pathologists criteria, circumferential resection margin-positive patients had shorter median overall survival (P < 0.0001) and shorter median disease-free survival (P < 0.0001) compared with circumferential resection margin-negative patients. The pooled hazard ratios for overall survival and disease-free survival were 2.06 (95% confidence interval, 1.68-2.53; P < 0.0001) and 2.00 (95% confidence interval, 1.41-2.84; P < 0.0001), respectively. According to the Royal College of Pathologists criteria, circumferential resection margin-positive patients had shorter median overall survival (P < 0.0001) and shorter median disease-free survival (P < 0.0001) compared with circumferential resection margin-negative patients. The pooled hazard ratios for overall survival and disease-free survival were 1.31 (95% confidence interval, 1.16-1.48; P < 0.0001) and 1.31 (95% confidence interval, 1.09-1.57; P < 0.0001), respectively.ompared with negative circumferential resection margin, positive circumferential resection margin is associated with worse survival outcomes in esophageal cancer.

Association of MALAT-1 gene single nucleotide polymorphisms with genetic susceptibility to systemic lupus erythematosus.

Background: Abnormal expression and function of long non-coding RNAs (lncRNAs) are closely related to the pathogenesis of systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) gene single-nucleotide polymorphisms (SNPs) with susceptibility and clinical characteristics of SLE patients. Methods: A case-control study including 489 SLE patients and 492 healthy controls was conducted. Four MALAT-1 SNPs (rs4102217, rs591291, rs11227209, and rs619586) were genotyped in all subjects, their correlation with SLE susceptibility and clinical characteristics were also analyzed. Results: Results showed that the rs4102217 locus was associated with the risk of SLE. In recessive models, the GG+CG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC (p = 0.036, OR = 0.348, 95% CI: 0.124-0.975). In additive models, the GG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC (p = 0.040, OR = 0.355, 95% CI: 0.127-0.996). However, no association was found between MALAT-1 gene polymorphism and clinical manifestations of SLE (all p > 0.05). Conclusion: In summary, MALAT-1 rs4102217 is associated with susceptibility to SLE, suggesting that MALAT-1 may play a role in SLE.

Emerging role of Fli1 in autoimmune diseases.

The Ets transcription factor family exerts crucial role in cell proliferation, apoptosis, differentiation and migration. Friend leukemia integration 1 (Fli1), a member of the Ets family, is expressed in fibroblasts, endothelial cells and immune cells. Fli1 gene is participated in the development, proliferation, activation, migration and other processes of immune cells. Fli1 can also affect the function of immune cells by regulating cytokines and chemokines. Emerging evidence has shown that Fli1 is implicated in the etiology of several autoimmune diseases, including systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). In this review, we mainly discuss the current evidence for the role of Fli1 in these diseases.

LncRNA-MALAT1 is a promising biomarker for prognostic evaluation of tongue squamous cell carcinoma.

PURPOSE: MALAT1 is recognized as an oncogenic lncRNA in various malignancies. Here, the authors aim to explore the association of MALAT1 expression and prognostic implication in tongue squamous cell carcinoma (SCC). METHODS: The tongue tissues of 128 tongue SCC cases satisfying strict follow-up criteria and 28 normal cases were subjected to qRT-PCR assay for monitoring MALAT1 expression. Chi-square test was applied to explore the correlation between MALAT1 expression and clinicopathological features of tongue SCC. Kaplan-Meier analysis was used to calculate survival rates. Cox proportional hazard analysis was adopted to analyze the relationship between prognostic factors and patient survival. RESULTS: The expression of MALAT1 was upregulated in tongue SCC, compared to normal tongue tissues. The expression level of MALAT1 was correlated to differentiation and stage of tongue SCC, and high MALAT1 expression was associated with low disease-free survival and overall survival rates. Moreover, advanced tongue SCC patients with high MALAT1 level had lower disease-free survival and decreased overall survival rate than patients with low MALAT1 level. These results revealed that MALAT1 overexpression can be considered as a significant prognostic factor to independently predict the disease-free survival and overall survival rate of tongue SCC. CONCLUSIONS: The expression level of MALAT1 is closely related with progression of tongue SCC. Furthermore, MALAT1 can serve as an independent biomarker for prognostic evaluation of tongue SCC.

Exendin­4 promotes osteogenic differentiation of adipose­derived stem cells and facilitates bone repair.

Inflammation­related bone defects pose a heavy burden on patients and orthopedic surgeons. Although stem­cell­based bone repair has developed rapidly, it is of great significance to characterize bio­active molecules that facilitate bone regeneration. It is reported that a glucagon­like peptide 1 receptor agonist, exendin­4, promoted bone regeneration mediated by the transplantation of adipose­derived stem cells in a metaphyseal defect mouse model of femur injury. However, the underlying mechanism is unclear. Bone imaging, immunohistochemistry real­time PCR and western blot analysis were used in the present study, and the results revealed that exendin­4 increased the transcription of the osteogenic differentiation­related genes and induced osteogenic differentiation in situ. Furthermore, the present data obtained from sorted adipose­derived stem cells revealed that exendin­4 promoted osteogenic differentiation and inhibited adipogenic differentiation in vitro. These findings indicated that exendin­4 facilitates osteogenic differentiation of transplanted adipose­derived stem cells for bone repair and illuminated clinical prospects of both adipose­derived stem cells and exendin­4 in stem­cell­based bone defect repair.

Optimization of betacyanins from agricultural by-products using pressurized hot water extraction for antioxidant and in vitro oleic acid-induced steatohepatitis inhibitory activity.

Pressurized hot water extraction (PHWE) is proposed to recover betacyanins from agricultural by-products (pitaya fruits peels (PFP), red beet stalks (RBS), and cactus pear peels (CPP)). The extraction yield of betacyanins was optimized by response surface methodology. The optimal PHWE conditions were attained and the actual yields of betacyanins under optimal conditions were well matched with the predicted yields. In addition, betacyanin pigment compositions as well as superoxide anion scavenging activity of individual betacyanins extract (BE) produced in optimal PHWE conditions were characterized by HPLC-ESI/MSn and cyclic voltammetry. Furthermore, the inhibitory activity of three BEs on oleic acid-induced steatohepatitis in cellular model was comparatively investigated. The results showed that unlike PFP, RBS, and CPP presented excellent efficacy in decreasing intracellular triglyceride and reactive oxygen species, inhibiting the release of alanine aminotransferase and aspartate aminotransferase as well as regulating fatty acid synthase and carnitine palmitoyltransferase 1 mRNAs expression. Practical applications In this study, PHWE, is firstly proposed for the enhancement of the extraction of betacyanins from three agricultural by-products. Betacyanin-rich extracts by PHWE method exhibit excellent activities in inhibition of ROS and regulation of lipid metabolism in hepatic cells. It suggests that PHWE has a strong potentiality in keeping bioactivity of BEs, which is significant for the production of betacyanins functional foods.

Prevalence and risk factors of atrial fibrillation during lung and esophageal surgery: A Prospective observational study.

The aim of this prospective observational study was to screen for risk factors of intraoperative atrial fibrillation (AF) during noncardiac thoracic surgery. The study was conducted as a single-institution study in Zhejiang Cancer Hospital, Hangzhou, China. All the participants were patients with cancer scheduled for thoracotomy.This study was conducted from July 2013 to August 2016 and included 144 patients scheduled for thoracotomy under general anesthesia. We collected the patients' demographic and perioperative medical data in our hospital. AF was diagnosed using electrocardiography (ECG), on the basis of the presence of characteristic ECG features of AF by one or more ECG leads for at least 30 seconds.Of the participants, 144 completed the study and 18 developed intraoperative AF. Higher percentages of subjects in the AF group than in the non-AF group had histories of chemotherapy (P = .014) and alcohol consumption (P = .034) before surgery. The AF group had a lower mean body mass index (P = .019), significantly higher mean heart rate (P < .001), and lower tidal volume (P = .01) than the non-AF group. After the logistic regression analysis, only alcohol consumption (odds ratio [OR] = 5.279; 95% confidence interval [CI]: 1.432-19.467), history of chemotherapy (OR = 4.019; 95% CI: 1.504-15.334), and high heart rate (OR = 1.093; 95% CI: 1.033-1.156) during 1-lung ventilation were identified as the risk factors of AF during lung and esophageal surgeries.The incidence of intraoperative AF during noncardiac thoracic surgery was 12.5%. Alcohol consumption, history of chemotherapy, and high heart rate during 1-lung ventilation were the risk factors related to intraoperative AF.

Hepatitis C virus NS4B protein induces epithelial-mesenchymal transition by upregulation of Snail.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is an important cause of hepatocellular carcinoma (HCC). Epithelial to mesenchymal transition (EMT) is a key process associated with tumor metastasis and poor prognosis. HCV infection, HCV core and NS5A protein could induce EMT process, but the role of NS4B on EMT remains poorly understood. METHODS: We overexpressed HCV NS4B protein in HepG2 cells or Huh7.5.1 cells infected by HCVcc, the E-cadherin expression, N-cadherin expression and the EMT-associated transcriptional factor Snail were determined. The migration and invasion capabilities of the transfected cells were evaluated using wound-healing assay. Additionally, we used Snail siRNA interference to confirm the relation of HCV NS4B and Snail on EMT promotion. RESULTS: HCV NS4B increased the expression of EMT related markers and promoted cell migration and invasion. Snail knock-down almost completely eliminated the function of NS4B protein in EMT changes and reversed cell migration capacity to lower level. HCV NS4B protein could reduce the expression of Scribble and Hippo signal pathway were subsequently inactivated, resulting in the activation of PI3K/AKT pathway, which may be the reason for the up-regulation of Snail. CONCLUSIONS: This study demonstrates that HCV NS4B protein induces EMT progression via the upregulation of Snail in HCC, which may be a novel underlying mechanism for HCV-associated HCC development, invasion and metastasis.

Dendritic cells infected by Ad-sh-SOCS1 enhance cytokine-induced killer (CIK) cell immunotherapeutic efficacy in cervical cancer models.

BACKGROUND AIMS: Cervical cancer constitutes a major problem in women's health worldwide, but the efficacy of the standard therapy is unsatisfactory. Cytokine-induced killer (CIK) cells exhibit antitumor activity against a variety of malignancies in preclinical models and have proven safe and effective in clinical trials. However, current CIK therapy has limitations and needs to be improved to meet the clinical requirements. The aim of this study was to investigate whether suppressing the expression of cytokine signaling 1 (SOCS1) in dendritic cells (DCs) can shorten in vitro CIK culture time and improve its antitumor efficacy. METHODS: DCs were pre-cultured for 3 days before infected with adenovirus-mediated-SOCS1 short hairpin RNA (Ad-sh-SOCS1) and pulsed with CTL epitope peptides E7. The DCs infected by Ad-sh-SOCS1 (gmDCs) and CIKs were then co-cultured for 5 or 9 days, and CIK proliferation and antitumor activity were evaluated both in vitro and in vivo. RESULTS: Our data show that gmDCs significantly stimulated the expansion of co-cultured CIKs and increased the secretion of interferon-γ and interleukin-12. Moreover, gmDCs-activated CIKs showed higher cytotoxic activity against TC-1 cells expressing HPV16E6 and E7. Our in vivo study showed that the mice infused with gmDCs-activated CIKs on day 10 had an increased survival rate and prolonged survival time compared with the controls. CONCLUSIONS: Taken together, these results indicate that DCs modified by adenovirus-mediated SOCS1 silencing can promote CIKs expansion and enhance the efficacy of antitumor immunotherapy both in vitro and in vivo, which represents an effective therapeutic approach for cervical cancer and other tumors.

HCV NS4B targets Scribble for proteasome-mediated degradation to facilitate cell transformation.

Hepatitis C virus (HCV) nonstructural protein 4B (NS4B) is a multi-transmembrane protein, but little is known about how NS4B contributes to HCV replication and tumorigenesis. Its C-terminal domain (CTD) has been shown to associate with intracellular membrane, and we have previously shown that NS4B CTD contains a class I PDZ-binding motif (PBM). Here, we demonstrated that NS4B PBM interacts with the PDZ-containing tumor suppressor protein, Scribble, using immunofluorescence and co-immunoprecipitation assays, and this interaction requires at least three contiguous PDZ domains of Scribble. In addition, NS4B PBM specifically induced Scribble degradation by activating the proteasome-ubiquitin pathway. Similar Scribble degradation was also observed in HCV-infected cells, suggesting NS4B could work in the context of HCV. Finally, NS4B PBM mutants showed reduced colony formation capacity compared with its wild-type counterpart, indicating that NS4B PBM plays important roles in NS4B-mediated cell transformation. Altogether, we provide a mechanism by which NS4B induces cell transformation through its PBM, which specifically interacts with the PDZ domains of Scribble and targets Scribble for degradation.

Macro- and micro-anatomical, histological and computed tomography scan characterization of the nasopalatine canal.

AIM: To determine the human anatomic variability of the nasopalatine canal and determine its characteristics using an anatomical, histological and computed tomography (CT) scan evaluation. MATERIALS AND METHODS: Measurements for the canal characteristics were carried out on 163 dry human skulls and 120 upper jaw spiral CT scans, taken from patients for pre-operative planning purposes of implant placement in the incisor region. Furthermore, four human cadaver specimens were imaged using a high-resolution magnetic resonance imaging (HR-MRI) unit. Afterwards, these specimens were serially sectioned for histological examination to evaluate the nasopalatine canal region and its content. RESULTS: The nasopalatine canal anatomy showed a large variability in morphology and dimensions, with the canal branching in up to four canals at the level of the nose. The canal diameter was on average 3.3 mm (+/-0.9 mm SD), and typically enlarged by age and male gender (p<0.05). HR-MRI and histological sections enabled to identify the neurovascular structures within the canals. CONCLUSIONS: The large anatomic variations, the increased canal dimensions with age and the neurovascular canal content are all factors favouring a thorough three-dimensional planning before surgery, such as implant placement, of the anterior maxillary region.