Retinopathy as a predictive indicator for significant hepatic fibrosis according to T2DM status: A cross-sectional study based on the national health and nutrition examination survey data.

INTRODUCTION AND OBJECTIVES: Type 2 Diabetes Mellitus (T2DM), a prevalent metabolic disorder, often coexists with a range of complications, with retinopathy being particularly common. Recent studies have shed light on a potential connection between diabetic retinopathy (DR) and hepatic fibrosis, indicating a possible shared pathophysiological foundation in T2DM. This study investigates the correlation between retinopathy and hepatic fibrosis among individuals with T2DM, as well as evaluates the diagnostic value of DR for significant hepatic fibrosis. MATERIALS AND METHODS: Our cross-sectional analysis incorporated 5413 participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2008. The Fibrosis-4 score (FIB-4) classified hepatic fibrosis into different grades (F0-F4), with significant hepatic fibrosis marked as F2 or higher. Retinopathy severity was determined using retinal imaging and categorized into four levels. The analysis of variance or Chi-square tests facilitated group comparisons. Additionally, the receiver operating characteristic (ROC) analysis appraised the predictive accuracy of retinopathy for significant hepatic fibrosis in the T2DM population. RESULTS: Among 5413 participants, the mean age was 59.56 ± 12.41, with 50.2% male. And 20.6% were diagnosed with T2DM. Hepatic fibrosis grading was positively associated with retinopathy severity (OR [odds ratio]: 1.521, 95%CI [confidence interval]: 1.152-2.008, P = 0.003) across the entire population. The association was amplified in the T2DM population according to Pearson's analysis results. The ROC curve demonstrated retinopathy's diagnostic capacity for significant hepatic fibrosis in the T2DM population (AUC [area under curve] = 0.72, 95%CI: 0.651-0.793, P < 0.001). CONCLUSIONS: Retinopathy could serve as an independent predictor of significant hepatic fibrosis in T2DM population. Ophthalmologists are advised to closely monitor T2DM patients with retinopathy.

Advances in the Biological Functions and Mechanisms of miRNAs in the Development of Osteosarcoma.

Osteosarcoma is one of the most common primary malignant bone tumors, mainly occurring in children and adolescents, and is characterized by high morbidity and poor prognosis. MicroRNAs, a class of noncoding RNAs consisting of 19 to 25 nucleotides, are involved in cell proliferation, invasion, metastasis, and apoptosis to regulate the development and progression of osteosarcoma. Studies have found that microRNAs are closely related to the diagnosis, treatment, and prognosis of osteosarcoma patients and have an important role in improving drug resistance in osteosarcoma. This paper reviews the role of microRNAs in the pathogenesis of osteosarcoma and their clinical value, aiming to provide a new research direction for diagnosing and treating osteosarcoma and achieving a better prognosis.

Highlight Every Step: Knowledge Distillation via Collaborative Teaching.

High storage and computational costs obstruct deep neural networks to be deployed on resource-constrained devices. Knowledge distillation (KD) aims to train a compact student network by transferring knowledge from a larger pretrained teacher model. However, most existing methods on KD ignore the valuable information among the training process associated with training results. In this article, we provide a new collaborative teaching KD (CTKD) strategy which employs two special teachers. Specifically, one teacher trained from scratch (i.e., scratch teacher) assists the student step by step using its temporary outputs. It forces the student to approach the optimal path toward the final logits with high accuracy. The other pretrained teacher (i.e., expert teacher) guides the student to focus on a critical region that is more useful for the task. The combination of the knowledge from two special teachers can significantly improve the performance of the student network in KD. The results of experiments on CIFAR-10, CIFAR-100, SVHN, Tiny ImageNet, and ImageNet datasets verify that the proposed KD method is efficient and achieves state-of-the-art performance.

Ultrasensitive electrochemical detection of hepatitis C virus core antigen using terminal deoxynucleotidyl transferase amplification coupled with DNA nanowires.

Early diagnosis of hepatitis C virus (HCV) infection is essential to prevent disease from spreading and progression. Herein, a novel electrochemical biosensor was developed for ultrasensitive detection of HCV core antigen (HCVcAg) based on terminal deoxynucleotidyl transferase (TdT) amplification and DNA nanowires (DNW). After sandwich-type antibody-antigen recognition, the antibody-conjugated DNA was pulled to the electrode surface and further extended into a long DNA sequence by robust TdT reaction. Then, large numbers of methylene blue-loaded DNW (MB@DNW) as signal labels are linked to the extended DNA sequence. This results in an amplified electrochemical signal for HCVcAg determination, typically measured at around -0.25 V (Ag/AgCl). Under the optimum conditions, the proposed biosensor achieved a wide linear range for HCVcAg from 0.1 to 312.5 pg/mL with a low limit of detection of 32 fg/mL. The good practicality of the biosensor was demonstrated by recovery experiment (recoveries from 98 to 104% with RSD of 2.5-4.4%) and comparison with enzyme-linked immunosorbent assay (ELISA). Given the highlighted performance, the biosensor is expected to act as a reliable sensing tool for HCVcAg determination in clinics. Schematic representation of the ultrasensitive electrochemical biosensor based on terminal deoxynucleotidyl transferase (TdT) amplification linked with methylene blue-loaded DNA nanowires (MB@DNW), which can be applied to the determination of hepatitis C virus core antigen (HCVcAg) in clinical samples. dTTPs, 2'-deoxythymidine 5'-triphosphate.

Identification of NUF2 and FAM83D as potential biomarkers in triple-negative breast cancer.

BACKGROUND: Breast cancer is a heterogeneous disease. Compared with other subtypes of breast cancer, triple-negative breast cancer (TNBC) is easy to metastasize and has a short survival time, less choice of treatment options. Here, we aimed to identify the potential biomarkers to TNBC diagnosis and prognosis. MATERIAL/METHODS: Three independent data sets (GSE45827, GSE38959, GSE65194) were downloaded from the Gene Expression Omnibus (GEO). The R software packages were used to integrate the gene profiles and identify differentially expressed genes (DEGs). A variety of bioinformatics tools were used to explore the hub genes, including the DAVID database, STRING database and Cytoscape software. Reverse transcription quantitative PCR (RT-qPCR) was used to verify the hub genes in 14 pairs of TNBC paired tissues. RESULTS: In this study, we screened out 161 DEGs between 222 non-TNBC and 126 TNBC samples, of which 105 genes were up-regulated and 56 were down-regulated. These DEGs were enriched for 27 GO terms and two pathways. GO analysis enriched mainly in "cell division", "chromosome, centromeric region" and "microtubule motor activity". KEGG pathway analysis enriched mostly in "Cell cycle" and "Oocyte meiosis". PPI network was constructed and then 10 top hub genes were screened. According to the analysis results of the Kaplan-Meier survival curve, the expression levels of only NUF2, FAM83D and CENPH were associated with the recurrence-free survival in TNBC samples (P < 0.05). RT-qPCR confirmed that the expression levels of NUF2 and FAM83D in TNBC tissues were indeed up-regulated significantly. CONCLUSIONS: The comprehensive analysis showed that NUF2 and FAM83D could be used as potential biomarkers for diagnosis and prognosis of TNBC.

Clinical significance of serum transforming growth factor-ß1 in lung cancer.

BACKGROUND: Transforming growth factor-ß1 (TGF-ß1) plays a critical role in human cancer development. Present study aimed to explore the clinical significance of serum TGF-ß1 levels in patients with lung cancer and analyze the relationship between TGF-ß1 and existing tumor markers for lung cancer. METHODS: Serum was collected from 118 patients with lung cancer and 40 healthy volunteers. Serum TGF-ß1 levels were measured by enzyme-linked immunosorbent assay (ELISA), and the association with various clinical characteristics was analyzed. The diagnostic value of TGF-ß1 was assessed alone and in combination with existing tumor markers for lung cancer. RESULTS: Serum TGF-ß1 levels were significantly higher in patients with lung cancer compared to healthy volunteers [0.6 × 10(5) (0.4 × 10(5), 0.9 × 10(5))pg/ml vs 0.5 × 10(5) (0.3 × 10(5), 0.7 × 10(5))pg/ml, P=0.040]. Although there was a positive correlation between serum TGF-ß1 levels and advanced stages, the significant difference was not found between early stages and advanced stages (P=0.116). The ability of serum TGF-ß1 to discriminate lung cancer at a cutoff value of 79,168 pg/ml exhibited sensitivity of 30.6% and specificity of 97.5%. Serum TGF-ß1 levels were correlated to cytokeratin fragment 21-1 (CYFRA21-1; R=0.308, P=0.020) and neuron-specific enolase (NSE; R=0.558, P=0.003). The diagnostic accuracy rates for the existing lung-tumor markers, as SCC, CYFRA21-1, and NSE, were increased from 20.0%, 34.6%, and 45.9% to 48.9%, 51.7%, and 54.5%, respectively by the inclusion of serum TGF-ß1 levels. CONCLUSION: Quantification of serum TGF-ß1 levels by ELISA may provide a novel complementary tool for the clinical diagnosis of lung cancer.

Quantification of plasma hTERT DNA in hepatocellular carcinoma patients by quantitative fluorescent polymerase chain reaction.

PURPOSE: To investigate the levels of human telomerase reverse transcriptase (hTERT) DNA in the plasma of patients with hepatocellular carcinoma (HCC), and to evaluate the diagnostic value and correlation of hTERT DNA with clinical parameters in HCC. METHODS: A real-time quantitative fluorescent polymerase chain reaction (FQ-PCR) system was designed and evaluated. Plasma samples were collected from 60 HCC patients, 21 patients with hepatitis B virus (HBV) and 29 healthy controls. Plasma DNA was extracted and quantified by FQ-PCR. The diagnostic value of plasma hTERT DNA levels and their relationships with clinical characteristics were analyzed statistically. RESULTS: Plasma levels of hTERT DNA in HCC patients were significantly higher than in HBV patients (4.18×104±4.94×104 copies/µl vs 1.21×104±6.63×103 copies/µl, P=0.003) and healthy controls (4.18×104±4.94×104 copies/µl vs 1.44×104±6.61×103 copies/µl, P < 0.001). Receiver operating characteristic curve analysis indicated a sensitivity of 64% and a specificity of 90% for the ability of hTERT DNA levels to detect malignancy at a cutoff value of 1.87×104 copies/µl. Association analysis revealed that plasma hTERT DNA levels were closely related to tumor size, portal vein cancer embolus and TNM stage (P=0.013, P=0.010, and P=0.029, respectively), but were not associated with lymph node metastasis, hepatitis B surface antigen, or α-fetoprotein (AFP) (all P > 0.05). The levels of plasma hTERT DNA in HCC patients with AFP ≤20 ng/ml were significantly higher than in HBV patients (4.59×104±4.98×104 copies/µl vs 1.44×104±6.63×103 copies/µl, P=0.016) and in healthy controls (4.59×104±4.98×104 copies/µl vs 1.21×104±6.63×103 copies/µl, P=0.001). CONCLUSIONS: Quantitation of plasma hTERT DNA by FQ-PCR may provide a novel complementary tool with potential clinical applications for the screening and detection of HCC. Plasma hTERT DNA has the potential to be a broad tumor marker for common cancers.