Epstein-Barr virus-positive iris diffuse large B-cell lymphoma detected by metagenomic next-generation sequencing.

PURPOSE: Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) is a relatively rare subtype of DLBCL. Herein, we report a case of a patient with EBV-positive iris DLBCL after undergoing penetrating keratoplasty and discuss its possible pathogenesis. METHODS: A 72-year-old male patient presented to our hospital with progressive blurring of vision in the left eye for the past 4 months. Small white nodular lesions were observed on the iris and retinal surface of the left eye, with a white cloud-like opacity in the vitreous cavity. RESULTS: The patient was eventually diagnosed with EBV-positive iris DLBCL after undergoing pathological and metagenomic tests. After injecting methotrexate in the left vitreous cavity and administering systemic and local antiviral treatments, the ocular lesions disappeared. CONCLUSION: EBV infection, drug immunosuppression, and aging-related immune deterioration may play significant roles in the pathogenesis of EBV-positive iris DLBCL. SYNOPSIS: Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) is a new subtype of DLBCL, which rarely occurs. Herein, we report a case of a patient with EBV-positive iris DLBCL after undergoing penetrating keratoplasty and discuss its possible pathogenesis.

RNA-binding protein IGF2BP2 suppresses metastasis of clear cell renal cell carcinoma by enhancing CKB mRNA stability and expression.

Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer, with a highly aggressive phenotype and poor prognosis. RNA binding proteins (RBPs) play crucial roles in post-transcriptional gene regulation and have been implicated in tumorigenesis. RBPs have the potential to become a new therapeutic target for ccRCC. In this study, we screened and validated that insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) as an RBP, was down-regulated in ccRCC tissues and cell lines. Functionally, we verified that IGF2BP2 significantly suppressed the migration and invasion ability of ccRCC in vitro and in vivo. Mechanistically, RIP-seq and actinomycin D experiments results showed that IGF2BP2 enhanced the expression of Creatine Kinase B (CKB) by binding to CKB mRNA and enhancing its mRNA stability. Thus, IGF2BP2 inhibited ccRCC metastasis through enhancing the expression of CKB. Taken together, these finding suggests that IGF2BP2 is a novel metastasis suppressor of ccRCC and may serve as a potential therapeutic target.

A novel peptide PDHK1-241aa encoded by circPDHK1 promotes ccRCC progression via interacting with PPP1CA to inhibit AKT dephosphorylation and activate the AKT-mTOR signaling pathway.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer with high aggressive phenotype and poor prognosis. Accumulating evidence suggests that circRNAs have been identified as pivotal mediators in cancers. However, the role of circRNAs in ccRCC progression remains elusive. METHODS: The differentially expressed circRNAs in 4 paired human ccRCC and adjacent noncancerous tissues ccRCC were screened using circRNA microarrays and the candidate target was selected based on circRNA expression level using weighted gene correlation network analysis (WGCNA) and the gene expression omnibus (GEO) database. CircPDHK1 expression in ccRCC and adjacent noncancerous tissues (n = 148) were evaluated along with clinically relevant information. RT-qPCR, RNase R digestion, and actinomycin D (ActD) stability test were conducted to identify the characteristics of circPDHK1. The subcellular distribution of circPDHK1 was analyzed by subcellular fractionation assay and fluorescence in situ hybridization (FISH). Immunoprecipitation-mass spectrometry (IP-MS) and immunofluorescence (IF) were employed to evaluate the protein-coding ability of circPDHK1. ccRCC cells were transfected with siRNAs, plasmids or lentivirus approach, and cell proliferation, migration and invasion, as well as tumorigenesis and metastasis in nude mice were assessed to clarify the functional roles of circPDHK1 and its encoded peptide PDHK1-241aa. RNA-sequencing, western blot analysis, immunoprecipitation (IP) and chromatin immunoprecipitation (ChIP) assays were further employed to identify the underlying mechanisms regulated by PDHK1-241aa. RESULTS: CircPDHK1 was upregulated in ccRCC tissues and closely related to WHO/ISUP stage, T stage, distant metastasis, VHL mutation and Ki-67 levels. CircPDHK1 had a functional internal ribosome entry site (IRES) and encoded a novel peptide PDHK1-241aa. Functionally, we confirmed that PDHK1-241aa and not the circPDHK1 promoted the proliferation, migration and invasion of ccRCC. Mechanistically, circPDHK1 was activated by HIF-2A at the transcriptional level. PDHK1-241aa was upregulated and interacted with PPP1CA, causing the relocation of PPP1CA to the nucleus. This thereby inhibited AKT dephosphorylation and activated the AKT-mTOR signaling pathway. CONCLUSIONS: Our data indicated that circPDHK1-encoded PDHK1-241aa promotes ccRCC progression by interacting with PPP1CA to inhibit AKT dephosphorylation. This study provides novel insights into the multiplicity of circRNAs and highlights the potential use of circPDHK1 or PDHK1-241aa as a therapeutic target for ccRCC.

Effect of ultrahigh pressure processing (UHP) on physicochemical properties, antioxidant activity and anti-inflammatory activity of insoluble dietary fiber from Pholiota nameko.

The aim of this study was to evaluate the effect of ultrahigh pressure processing (UHP) of 200, 300, 400, 500, 600 and 700 MPa for 20, 40 and 30 min on physicochemical and bioactive properties of the insoluble dietary fiber Pholiota nameko (PN-IDF). The results revealed that UHP were capable of decreasing the particle size of PN-IDF and binding phenolic content. Moreover, UHP technique had an improving effect on the bioaccessible phenolic content, the water-holding capacity, the oil-holding capacity and the nitrite ion adsorption capacity. Further, UHP technique presented a promoting effect on the antioxidant activity by scavenging ABTS or DPPH free radicals and increasing reducing power, and the anti-inflammatory activity by inhibiting carrageenan-induced paw edema on PN-IDF. Overall, this study well proved that UHP technology could improve the physicochemical and functional quality of PN-IDF, which could be used as a promising green technique for functional food ingredients processing.

RNA Binding Protein PTBP1 Promotes the Metastasis of Gastric Cancer by Stabilizing PGK1 mRNA.

Gastric cancer (GC) is the most common type of malignant tumor within the gastrointestinal tract, and GC metastasis is associated with poor prognosis. Polypyrimidine tract binding protein 1 (PTBP1) is an RNA-binding protein implicated in various types of tumor development and metastasis. However, the role of PTBP1 in GC metastasis remains elusive. In this study, we verified that PTBP1 was upregulated in GC tissues and cell lines, and higher PTBP1 level was associated with poorer prognosis. It was shown that PTBP1 knockdown in vitro inhibited GC cell migration, whereas PTBP1 overexpression promoted the migration of GC cells. In vivo, the knockdown of PTBP1 notably reduced both the size and occurrence of metastatic nodules in a nude mice liver metastasis model. We identified phosphoglycerate kinase 1 (PGK1) as a downstream target of PTBP1 and found that PTBP1 increased the stability of PGK1 by directly binding to its mRNA. Furthermore, the PGK1/SNAIL axis could be required for PTBP1's function in the promotion of GC cell migration. These discoveries suggest that PTBP1 could be a promising therapeutic target for GC.

Evaluation of the efficacy and safety of CalliSpheres® microsphere-transarterial chemoembolization in large hepatocellular carcinoma.

OBJECTIVE: The prognosis of large hepatocellular carcinoma (HCC) is still unfavorable due to limited and challenging treatment. CalliSpheres® microsphere-transarterial chemoembolization (CSM-TACE) is an effective therapy for general HCC but not frequently applied for large HCC. Hence, this study aimed to investigate the efficacy and safety of CSM-TACE in large HCC patients. MATERIALS AND METHODS: This prospective study analyzed 100 large HCC (tumor size >5 cm) patients receiving CSM-TACE. Treatment response, survival, change in liver function indexes, and adverse events were recorded. RESULT: The best complete response, partial response, stable disease, and progressive disease rates were 2.0%, 31.3%, 65.7%, and 1.0%, respectively, leading to the best objective response rate (ORR) of 33.3% and disease control rate of 99.9%. Multivariate analysis showed that intrahepatic metastasis was independently related to poor ORR (odd ratio = 0.366, P = 0.023). The 1- and 2-year progression-free survival (PFS) rates were 88.9% and 80.6%, with a mean [95% confidence interval (CI)] PFS of 21.6 (20.4-22.9) months. The 1- and 2-year overall survival (OS) rates were 99.0% and 99.0%, with a mean (95% CI) OS of 23.8 (23.3-24.2) months. Total bilirubin (P < 0.001), alanine transaminase (P < 0.001), aspartate transaminase (P < 0.001), and α-fetoprotein (P = 0.045) were abnormal in a short-term period then stably recovered from 1 month ± 15 days after drug-eluting bead-TACE to 24 months ± 15 days. During hospitalization and postdischarge, tolerable abdominal pain and decreased appetite were common adverse events. CONCLUSIONS: CSM-TACE shows favorable treatment response and survival with acceptable tolerance among large HCC patients, indicating that it may promote the management of these patients.

CircNFATC3 promotes the proliferation of gastric cancer through binding to IGF2BP3 and restricting its ubiquitination to enhance CCND1 mRNA stability.

BACKGROUND: Insulin like growth factor II mRNA binding protein 3 (IGF2BP3) is an RNA binding protein with multiple roles in regulation of gene expression at the post-transcriptional level and is implicated in tumorigenesis and progression of numerous cancers including gastric cancer (GC). Circular RNAs (circRNAs) are a diverse endogenous noncoding RNA population that have important regulatory roles in cancer. However, circRNAs that regulate the expression of IGF2BP3 in GC is largely unknown. METHODS: CircRNAs that bound to IGF2BP3 were screened in GC cells using RNA immunoprecipitation and sequencing (RIP-seq). The identification and localization of circular nuclear factor of activated T cells 3 (circNFATC3) were identified using Sanger sequencing, RNase R assays, qRT-PCR, nuclear-cytoplasmic fractionation and RNA-FISH assays. CircNFATC3 expression in human GC tissues and adjacent normal tissues were measured by qRT-PCR and ISH. The biological role of circNFATC3 in GC was confirmed by in vivo and in vitro experiments. Furthermore, RIP, RNA-FISH/IF, IP and rescue experiments were performed to uncover interactions between circNFATC3, IGF2BP3 and cyclin D1 (CCND1). RESULTS: We identified a GC-associated circRNA, circNFATC3, that interacted with IGF2BP3. CircNFATC3 was significantly overexpressed in GC tissues and was positively associated with tumor volume. Functionally, the proliferation of GC cells decreased significantly after circNFATC3 knockdown in vivo and in vitro. Mechanistically, circNFATC3 bound to IGF2BP3 in the cytoplasm, which enhanced the stability of IGF2BP3 by preventing ubiquitin E3 ligase TRIM25-mediated ubiquitination, thereby enhancing the regulatory axis of IGF2BP3-CCND1 and promoting CCND1 mRNA stability. CONCLUSIONS: Our findings demonstrate that circNFATC3 promotes GC proliferation by stabilizing IGF2BP3 protein to enhance CCND1 mRNA stability. Therefore, circNFATC3 is a potential novel target for the treatment of GC.

Detection of methyltransferase activity and inhibitor screening based on rGO-mediated silver enhancement signal amplification strategy.

DNA methylation refers to the chemical modification process of obtaining a methyl group by the covalent bonding of a specific base in DNA sequence with S-adenosyl methionine (SAM) as a methyl donor under the catalysis of methyltransferase (MTase), which is related to the occurrence of multiple diseases. Therefore, the detection of MTase activity is of great significance for disease diagnosis and drug screening. Because reduced graphene oxide (rGO) has a unique planar structure and remarkable catalytic performance, it is not clear whether rGO can rapidly catalyze silver deposition as an effective way of signal amplification. However, in this study, we were pleasantly surprised to find that using H2O2 as a reducing agent, rGO can rapidly catalyze silver deposition, and its catalytic efficiency of silver deposition is significantly better than that of GO. Therefore, based on further verifying the mechanism of catalytic properties of rGO, we constructed a novel electrochemical biosensor (rGO/silver biosensor) for the detection of dam MTase activity, which has high selectivity and sensitivity to MTase in the range of 0.1 U/mL to 10.0 U/mL, and the detection limit is as low as 0.07 U/mL. Besides, this study also used Gentamicin and 5-Fluorouracil as inhibitor models, confirming that the biosensor has a good application prospect in the high-throughput screening of dam MTase inhibitors.

A Phase 1/2 Multicenter Randomized Trial of Local Ablation plus Toripalimab versus Toripalimab Alone for Previously Treated Unresectable Hepatocellular Carcinoma.

PURPOSE: To assess the safety and efficacy of local ablation plus PD-1 inhibitor toripalimab in previously treated unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: In the multicenter, two-stage, and randomized phase 1/2 trial, patients were randomly assigned to receive toripalimab alone (240 mg, every 3 weeks), subtotal local ablation followed by toripalimab starting on post-ablation day 3 (Schedule D3), or on post-ablation day 14 (Schedule D14). The first endpoint of stage 1 was to determine which combination schedule could continue and progression-free survival (PFS) as the primary endpoint for stage 1/2. RESULTS: A total of 146 patients were recruited. During stage 1, Schedule D3 achieved numerically higher objective response rate (ORR) than Schedule D14 for non-ablation lesions (37.5% vs. 31.3%), and was chosen for stage 2 evaluation. For the entire cohort of both stages, patients with Schedule D3 had a significantly higher ORR than with toripalimab alone (33.8% vs. 16.9%; P = 0.027). Moreover, patients with Schedule D3 had improved median PFS (7.1 vs. 3.8 months; P < 0.001) and median overall survival (18.4 vs. 13.2 months; P = 0.005), as compared with toripalimab alone. In addition, six (9%) patients with toripalimab, eight (12%) with Schedule D3, and 4 (25%) with Schedule D14 developed grade 3 or 4 adverse events, and one patient (2%) with Schedule D3 manifested grade 5 treatment-related pneumonitis. CONCLUSIONS: In patients with previously treated unresectable HCC, subtotal ablation plus toripalimab improved the clinical efficacy as compared with toripalimab alone, with an acceptable safety profile.

A bioinformatics analysis of the susceptibility genes in Stanford type A aortic dissection.

Background: The expression levels of long noncoding RNAs (lncRNAs) and mRNAs in human acute Stanford type A aortic dissecting aneurysm and normal active vascular tissues were compared using the array lncRNA/mRNA expression profile chip technology. Methods: The tissue samples of 5 patients who presented with Stanford type A aortic dissections and the normal ascending aorta tissues from 5 donor heart transplantation patients receiving surgical treatment in Ganzhou People's Hospital were collected. Hematoxylin and eosin (HE) staining were performed to investigate the structural features of the ascending aortic vascular tissue. Nanodropnd-100 was used to detect the surface level of RNA in 10 samples included in the experiment, to ensure that the quality of the standard was consistent with the core plate detection. NanoDrop ND-1000 was used to detect the RNA expression levels in 10 specimens included in the experiment to ensure that the quality of specimens satisfied the requirements of the microarray detection experiment. The Arraystar Human LncRNA/mRNAV3.0 expression profile chip (8×60K, Arraystar) was used to detect the expression levels of lncRNAs and mRNAs in the tissue samples. Results: A total of 29,198 lncRNAs and 22,959 mRNA target genes could be detected in the above tissue samples after the initial data were standardized and low-expression information was filtered. The data in the middle of the range of 50% value consistency was higher. The scatterplot results preliminarily suggested that there were large numbers of lncRNAs with increased and decreased expression in Stanford type A aortic dissection tissues compared with normal aortic tissues. The differentially expressed lncRNAs were enriched in BPs including apoptosis, nitric oxide synthesis, estradiol response, angiogenesis, inflammatory response, oxidative stress, and acute response; cell components (CCs) including cytoplasm, nucleus, cytoplasmic matrix, extracellular space, protein complex, and platelet α granule lumen; and MFs including protease binding, zinc ion binding, steroid compound binding, steroid hormone receptor activity, heme binding, protein kinase, cytokine, superoxide dismutase, and nitric oxide synthase activities. Conclusions: Gene ontology analysis demonstrated that many genes in Stanford type A aortic dissection were involved in cell biological functions, cell components, and molecular functions through upregulating and downregulating the levels of expression.

Signal Amplification-Based Biosensors and Application in RNA Tumor Markers.

Tumor markers are important substances for assessing cancer development. In recent years, RNA tumor markers have attracted significant attention, and studies have shown that their abnormal expression of post-transcriptional regulatory genes is associated with tumor progression. Therefore, RNA tumor markers are considered as potential targets in clinical diagnosis and prognosis. Many studies show that biosensors have good application prospects in the field of medical diagnosis. The application of biosensors in RNA tumor markers is developing rapidly. These sensors have the advantages of high sensitivity, excellent selectivity, and convenience. However, the detection abundance of RNA tumor markers is low. In order to improve the detection sensitivity, researchers have developed a variety of signal amplification strategies to enhance the detection signal. In this review, after a brief introduction of the sensing principles and designs of different biosensing platforms, we will summarize the latest research progress of electrochemical, photoelectrochemical, and fluorescent biosensors based on signal amplification strategies for detecting RNA tumor markers. This review provides a high sensitivity and good selectivity sensing platform for early-stage cancer research. It provides a new idea for the development of accurate, sensitive, and convenient biological analysis in the future, which can be used for the early diagnosis and monitoring of cancer and contribute to the reduction in the mortality rate.

Analysis of Clinical Characteristics of Patients with Recurrent Cytomegalovirus Retinitis after Hematopoietic Stem Cell Transplantation.

OBJECTIVE: To analyze and summarize the clinical and imaging characteristics of patients with cytomegalovirus retinitis (CMVR) relapse after hematopoietic stem cell transplantation (HSCT). METHODS: This retrospective case series study recruited patients with CMVR after HSCT. The study compared the patients with stable lesions and CMV-negative aqueous humor after treatment with those with relapse lesions and a CMV DNA load in aqueous humor which had increased again after treatment. The observation indexes were basic clinical information, best-corrected visual acuity, wide-angle fundus photography, optical coherence tomography (OCT), blood CD4+ T lymphocyte count, and aqueous humor CMV load of the patients. We summarized the data and statistically analyzed the differences between the relapse and non-relapse groups, as well as the correlations of the observed indicators. RESULTS: The study recruited 52 patients with CMVR (82 eyes) after HSCT, of whom 11 patients (15 eyes) had recurrence after treatment (21.2%). The recurrence interval was 6.4 ± 4.9 months. The final best-corrected visual acuity of recurrent patients was 0.3 ± 0.3. The number of CD4+ T lymphocytes in recurrence patients at the time of onset was 126.7 ± 80.2/mm3. The median CMV DNA load detected in aqueous humor at the time of recurrence was 8.63 × 103 copies/mL. There was a significant difference in the CD4+ T lymphocyte count between the recurrence and the non-recurrence groups at onset. The onset of visual acuity in recurrence patients was significantly correlated with final visual acuity and recurrence lesion area. The fundus of recurred CMVR showed increased marginal activity of the original stable lesion. Concurrently, yellow-white new lesions appeared around the stable, atrophic, and necrotic lesions. OCT showed new diffuse hyperreflexic lesions in the retinal neuroepithelial layer near the old lesions. Inflammatory punctate hyperreflexes were observed in the vitreous, with vitreous liquefaction and contraction. CONCLUSION: This study suggests that the clinical features, fundus manifestations, and imaging features of CMVR recurrence after HSCT are different from those at the initial onset. Patients should be closely followed up after their condition is stable to be alert for CMVR recurrence.

Role of the KRT7 Biomarker in Immune Infiltration and Paclitaxel Resistance in Ovarian.

Context: Paclitaxel (PTX) resistance is often associated with poor outcomes for patients with ovarian cancer (OC), but its mechanism is unknown. Clinicians are increasingly using immunotherapy in the management of OC, and the ability to assess tumor-immune interactions and identify effective, predictive, prognostic molecular biomarkers for OC is an urgent need. Objective: The study intended to explore the potential tumorigenesis mechanisms to identify promising biomarkers and improve survival in OC patients. Design: The research team performed a genetic analysis. Setting: The study took place at First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China. Outcome Measures: The research team: (1) obtained GSE66957 and GSE81778 gene expression profiles from the Gene Expression Omnibus (GEO) database and identified 468 differentially expressed genes (DEGs); (2) conducted functional enrichment analysis and constructed a protein-to-protein interaction (PPI) network; (3) identified the OC survival-related genes using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) webserver and compared those genes with upregulated DEGs to identify the core genes; (4) used GEPIA2 and the Kaplan-Meier plotter to explore the expression profiles and the prognostic values of the core genes in OC; (5) used the LinkOmics, Oncomine, and GEPIA2 web servers to perform co-expression analysis and explore functional networks correlated with keratin 7 (KRT7); (6) performed correlation analyses between KRT7, the six main types of tumor-infiltrating lymphocytes (TILs), and immune signatures, using the TIMER tool; and (7) subsequently detected the KRT7 expression in the cell lines IOSE80, A2780, A2780/PTX, ho8910, skov3, and ovcar3 using quantitative reverse transcription-polymerase chain reaction (RT-qPCR) technology. Results: High expression levels of KRT7 were significantly correlated with progression-free survival (PFS) and poor overall survival (OS) for OC patients, with logrank P = .0074 and logrank P = .014, respectively. The expression levels of KRT7 were also significantly correlated with the infiltrated neutrophil levels (r = 0.169, P = .0077). The study identified neutrophils as potential predictors of survival in OC. Moreover, the expression levels of KRT7 in OC were positively correlated with 51 (31.68%) of the 161 immune gene markers. The RT-qPCR analyses revealed a high expression of KRT7 in the paclitaxel-resistant OC cell line. Conclusions: KRT7 is correlated with immune infiltration and paclitaxel resistance in OC patients. Therefore, clinicians could use KRT7 as a prognostic marker and a target in the development of new drugs.

A method for reducing thermal injury during the ureteroscopic holmium laser lithotripsy.

Objective: Many studies have demonstrated the heat effect from the holmium laser lithotripsy can cause persistent thermal injury to the ureter. The purpose of this study was to elucidate the use of a modified ureteral catheter with appropriate firing and irrigation to reduce the thermal injury to the "ureter" during the ureteroscopic holmium laser lithotripsy in vitro. Methods: An in vitro lithotripsy was performed using a modified catheter (5 Fr) as the entrance for the irrigation and the holmium laser fiber while using the remaining space in the ureteroscopic channel as an outlet. Different laser power settings (10 W, 20 W, and 30 W) with various firing times (3 s, 5 s, and 10 s) and rates of irrigation (15 mL/min, 20 mL/min, and 30 mL/min) were applied in the experiment. Temperature changes in the "ureter" were recorded with a thermometer during and after the lithotripsy. Results: During the lithotripsy, the local highest mean temperature was 60.3 °C and the lowest mean temperature was 26.7 °C. When the power was set to 10 w, the temperature was maintained below 43 °C regardless of laser firing time or irrigation flow. Regardless of the power or firing time selected, the temperature was below 43 °C at the rate of 30 mL/min. There was a significant difference in temperature decrease when continuous 3 s drainage after continuous firing (3 s, 5 s, or 10 s) compared to with not drainage (p<0.05) except for two conditions of 0.5 J×20 Hz, 30 mL/min, firing 5 s, and 1.0 J×10 Hz, 30 mL/min, firing 5 s. Conclusion: Our modified catheter with timely drainage reducing hot irrigation may significantly reduce the local thermal injury effect, especially along with the special interrupted-time firing setting during the simulated holmium laser procedure.

miR-195-5p Targets CDK1 To Regulate New DNA Synthesis and Inhibit the Proliferation of Hepatocellular Carcinoma Cells.

In cell biological functions and viability, cyclin-dependent kinase 1 (CDK1) takes an essential part. miR-195-5p is pivotal in pathogenesis and development of hepatocellular carcinoma (HCC). But in HCC, whether there is a connection between CDK1 and miR-195-5p remains an unanswered question. In view of this, this study focuses on exploring the mechanism of miR-195-5p/CDK1 in the progression of HCC. The bioinformatics method was applied to predict target mRNA and upstream miRNAs, and further analyzes the signal enrichment pathway of target mRNA. We utilized qRT-PCR and Western blot for detecting expression of genes, as well as their corresponding protein levels. Cell cycle was assayed through flow cytometry. As for the examination of DNA replication, the EDU staining was employed. Cell proliferation was determined via plate colony formation assay. The combined application of bioinformatics analysis and dual-luciferase gene assay assisted in figuring out the binding relationship between miR-195-5p and CDK1. DNA damage was marked by immunofluorescence staining. CDK1 was overexpressed in HCC cells, and enriched in cell cycle and DNA replication pathway. Silencing CDK1 modulated cell cycle of HCC cells and inhibited DNA replication and proliferation. In HCC cells, miR-195-5p targeted and reduced CDK1 expression, inhibited the G1 phase-to-S phase transition, induced DNA damage response, and inhibited DNA replication and proliferation. miR-195-5p targeted CDK1 and repressed synthesis of new DNA in HCC cells, thus restraining HCC cell proliferation.

Health Education and Nursing Needs of Breast Cancer Patients With Totally Implantable Venous Access Ports at Different Stages.

Context: The totally implantable venous access port (TIVAP) is an intravenous-infusion device, with a lower complication rate than other such devices. If patients fail to maintain the catheter, however, complications can still occur. Patients' needs may vary by the period of the port's use. Objective: The study intended to explore the differences in the needs of breast-cancer (BC) patients with TIVAPs for health education and nursing care at different periods of the port's use and to determine the kinds of targeted health education that can improve patients' quality of life. Design: The research team designed a questionnaire that the participants completed. Setting: The study took place at the Breast Center at the Fourth Hospital of Hebei Medical University in Shijiazhuang, China. Participants: Participants were 442 BC patients at the hospital between March and June 2020, who had TIVAPs at different stages. Groups: The study included three groups: (1) the preoperative group-participants in the preoperative period prior to the TIVAP implantation after they had signed a consent; (2) the chemotherapy group-participants in the chemotherapy period during the TIVAP's use for chemotherapy-agent transfusion, and (3) the maintenance group-participants in the maintenance period during which the TIVAD was in place but wasn't being used. Outcome Measures: The research team analyzed the results from the questionnaires, categorizing them as: (1) methods of knowledge acquisition, (2) methods of distribution of knowledge, (3) needs of participants in the different groups, and (4) distribution of symptoms among the groups. Results: Compared to other methods, the nursing staff was the main source that participants used to access the TIVAP-related information at different periods: preoperative group (79.6%), chemotherapy group (90.7%), and maintenance group (90.2%).The differences between the periods were statistically significant (P = .00). A traditional mode of education-the medical staff's explanations-was the most common in all groups: preoperative group (79.6%), chemotherapy group (83.3%), and (3) maintenance group (80.7%). Patients wanted new modes of receiving information: talks, a poster, and a medical system. TIVAP patients paid different amounts of attention to educational contents at the different stages (χ2 = 29.816, P = .00). Conclusions: BC patients' needs for health education and nursing vary at different stages when using TIVAPs. Nurses are the main source of knowledge about TIVAP in different periods for BC patients, and the nurses should obtain multidisciplinary health knowledge to enhance the benefits of the education for patients. The current education for patient is traditional, and hospitals need to implement new modes of education such as medical systems and network platforms, lectures, and posters for health education.

Design and Implementation of Taizhou Integrated Prostate Screening.

A community-based prostate cancer screening program was conducted to assess the morbidity and associated factors for prostate cancer among the subpopulation of men aged ≥50 years in Taizhou, China. Taizhou Integrated Prostate Screening (TIPS) is a large, observational, population-based study of prostate cancer screening data based on serum prostate-specific antigen (PSA) concentrations. A pilot census of all male residents aged 50 years or older was conducted in Luqiao District, one of the field sites of the TIPS cohort in the city of Taizhou, Zhejiang. The interviewer-administered questionnaire evaluated demographic characteristics and environmental exposure factors. A total of 1,806 out of 3,516 participants completed the questionnaire. The overall prevalence of PSA ≥4 ng/mL was 11.5%, and included participants at low risk (9.2%), moderate risk (1.7%), and high risk (0.6%). Participants aged 60-69, 70-79, and ≥80 years had a 2.7-fold, 4.2-fold, and 6.5-fold higher risk of elevated PSA, respectively, in comparison with those aged 50 to 59 years (p < .001). Eighteen patients were diagnosed with prostate cancer, of whom 11 (61.1%) underwent radical surgery. This community-based PSA screening program indicated the results for early detection of prostate cancer among men aged ≥50 years. Early screening and appropriate clinical therapy for the management of prostate cancer are essential in this subpopulation.

CircARID1A binds to IGF2BP3 in gastric cancer and promotes cancer proliferation by forming a circARID1A-IGF2BP3-SLC7A5 RNA-protein ternary complex.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors in China. Circular RNAs (circRNAs) are novel non-coding RNAs with important regulatory roles in cancer progression. IGF2BP3 has been found to play oncogenic roles in various cancers including GC, while the exact mechanism of IGF2BP3 is largely unknown. METHODS: The expression of IGF2BP3 in GC was evaluated by Western Blot and bioinformatics analysis. CircRNA expression profiles were screened via IGF2BP3 RIP-seq in GC. Sanger sequencing, RNase R digestion, nucleo-plasmic separation and RNA-FISH assays were used to detect the existence and expression of circARID1A. RNA ISH assay was employed to test the expression of circARID1A in paraffin-embedded GC tissues. Moreover, the function of circARID1A on cellular proliferation was assessed by CCK-8, plate colony formation, EdU assays and GC xenograft mouse model in vivo. Furthermore, the location or binding of circARID1A, IGF2BP3 protein and SLC7A5 in GC was evaluated by RNA-FISH/IF or RNA pull-down assays. RESULTS: We identified a novel circRNA, circARID1A, that can bind to IGF2BP3 protein. CircARID1A was significantly upregulated in GC tissues compared with noncancerous tissues and positively correlated with tumor length, tumor volume, and TNM stage. CircARID1A knockdown inhibited the proliferation of GC cells in vitro and in vivo and circARID1A played an important role in the oncogenic function of IGF2BP3. Mechanistically, circARID1A served as a scaffold to facilitate the interaction between IGF2BP3 and SLC7A5 mRNA, finally increasing SLC7A5 mRNA stability. Additionally, circARID1A was able to directly bind SLC7A5 mRNA through complementary base-pairing and then formed the circARID1A-IGF2BP3-SLC7A5 RNA-protein ternary complex and promoted the proliferation of GC via regulating AKT/mTOR pathway. CONCLUSIONS: Altogether, our data suggest that circARID1A is involved in the function of IGF2BP3 and GC proliferation, and the circARID1A-IGF2BP3-SLC7A5 axis has the potential to serve as a novel therapeutic target for GC.

In Situ Silver-Based Electrochemical Oncolytic Bioreactor.

In this study, it is shown for the first time that a reduced graphene oxide (rGO) carrier has a 20-fold higher catalysis rate than graphene oxide in Ag+ reduction. Based on this, a tumor microenvironment-enabled in situ silver-based electrochemical oncolytic bioreactor (SEOB) which switched Ag+ prodrugs into in situ therapeutic silver nanoparticles with and above 95% transition rate is constructed to inhibit the growths of various tumors. In this SEOB-enabled intratumoral nanosynthetic medicine, intratumoral H2 O2 and rGO act as the reductant and the catalyst, respectively. Chelation of aptamers to the SEOB-unlocked prodrugs increases the production of silver nanoparticles in tumor cells, especially in the presence of Vitamin C, which is broken down in tumor cells to supply massive amounts of H2 O2 . Consequently, apoptosis and pyroptosis are induced to cooperatively contribute to the considerably-elevated anti-tumor effects on subcutaneous HepG2 and A549 tumors and orthotopic implanted HepG2 tumors in livers of nude mice. The specific aptamer targeting and intratumoral silver nanoparticle production guarantee excellent biosafety since it fails to elicit tissue damages in monkeys, which greatly increases the clinical translation potential of the SEOB system.