Diagnostic values of contrast-enhanced MRI and contrast-enhanced CT for evaluating the response of hepatocellular carcinoma after transarterial chemoembolisation: a meta-analysis.

OBJECTIVES: To assess and compare the diagnostic value of contrast-enhanced MRI (CEMRI) and contrast-enhanced CT (CECT) for evaluating the response of hepatocellular carcinoma (HCC) after transarterial chemoembolisation (TACE). DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, the Cochrane Library, CNKI and Wanfang databases were systematically searched from inception to 1 August 2023. ELIGIBILITY CRITERIA: Studies with any outcome that demonstrates the diagnostic performance of CEMRI and CECT for HCC after TACE were included. DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted the data and assessed the quality of included studies. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. The diagnostic performance of CEMRI and CECT for the response of HCC was investigated by collecting true and false positives, true and false negatives, or transformed-derived data from each study to calculate specificity and sensitivity. Other outcomes are the positive likelihood ratio/negative likelihood ratio (NLR), the area under the receiver operating characteristic curve (AUC) for diagnostic tests and the diagnostic OR (DOR). Findings were summarised and synthesised qualitatively according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: This study included 5843 HCC patients diagnosed with CEMRI or CECT and treated with TACE from 36 studies. The mean proportion of men in the total sample was 76.3%. The pool sensitivity, specificity and AUC of CEMRI in diagnosing HCC after TACE were 0.92 (95% CI: 0.86 to 0.96), 0.94 (95% CI: 0.86 to 0.98) and 0.98 (95% CI: 0.96 to 0.99). The pool sensitivity, specificity and AUC of CECT in diagnosing HCC after TACE were 0.74 (95% CI: 0.68 to 0.80), 0.98 (95% CI: 0.93 to 1.00) and 0.90 (95% CI: 0.88 to 0.93). CONCLUSIONS: In conclusion, this study found that both CEMRI and CECT had relatively high predictive power for assessing the response of HCC after TACE. Furthermore, the diagnostic value of CEMRI may be superior to CECT in terms of sensitivity, AUC, DOR and NLR.

Ultrasound-triggered with ROS-responsive SN38 nanoparticle for enhanced combination cancer immunotherapy.

Controlled generation of cytotoxic reactive oxygen species (ROS) is essential in cancer therapy. Ultrasound (US)-triggered sonodynamic therapy (SDT) has shown considerable ability to trigger in situ ROS generation. Unfortunately, US therapy alone is insufficient to trigger an efficient anticancer response, owing to the induction of multiple immunosuppressive factors. It was identified that 7-ethyl-10-hydroxycamptothecin (SN38) could notably inhibit DNA topoisomerase I, induce DNA damage and boost robust anticancer immunity. However, limited by the low metabolic stability, poor bioavailability, and dose-limiting toxicity, the direct usage of SN38 is inadequate in immune motivation, which limits its clinical application. Hence, new strategies are needed to improve drug delivery efficiency to enhance DNA topoisomerase I inhibition and DNA damage and elicit a vigorous anticancer cancer immunity response. Considering US irradiation can efficiently generate large amounts of ROS under low-intensity irradiation, in this study, we aimed to design a polymeric, ROS-responsive SN38 nanoformulation for in vivo drug delivery. Upon the in-situ generation of ROS by US therapy, controlled on-demand release of SN38 occurred in tumor sites, which enhanced DNA damage, induced DC cell maturation, and boosted anticancer immunity. Our results demonstrated that a new strategy of involving the combination of a SN38 nanoformulation and US therapy could be used for cancer immunotherapy.

Comparative efficacy and safety of four common balloon angioplasty techniques for an arteriovenous fistula or graft stenosis: a systematic review and network meta-analysis of randomized controlled trials.

Background: Balloon angioplasty could decrease restenosis of hemodialysis vascular access. The present study investigated the comparative effects and safety of commonly available balloon angioplasty techniques for treating patients with failing autogenous arteriovenous fistulas (AVFs) and grafts (AVGs) stenosis. Methods: A comprehensive literature search, including an updated search of PubMed and Embase (via Ovid) and screening of published meta-analyses, was conducted. Primary patency at 6 and 12 months was the primary outcome, and the incidence of complications was the secondary outcome. The random-effects model was used to conduct all statistical analyses, which were performed using RevMan 5.3 and ADDIS 1.16.8. Results: A total of 20 eligible studies involving four balloon angioplasty techniques were entered into the final analysis. Although the direct meta-analysis indicated that cutting balloon angioplasty (CtBA) significantly improved primary patency at 6 [odds ratio (OR), 1.91; 95% confidence interval (CI): 1.27 to 2.86] and 12 (OR, 1.56; 95% CI: 1.13 to 2.15) months compared with conventional balloon angioplasty (CBA), this was not supported by network meta-analysis, which suggested that CtBA was associated with a higher risk of complications compared with drug-coated balloon angioplasty (DcBA) [OR, 0.05; 95% credible interval (CrI): 0.00 to 0.83], high-pressure balloon angioplasty (HBA) (OR, 0.04; 95% CrI: 0.00 to 0.69), and CBA (OR, 0.11; 95% CrI: 0.02 to 0.59). Subgroup analysis of AVFs did not detect any significant differences. Conclusions: In failing AVF and AVG stenosis, HBA might be a preferential option as it is related to a lower risk of complications and has numerically higher primary patency than DcBA and CBA. Further studies are needed to confirm these findings.

Identification and Validation of Hub Genes in the Stenosis of Arteriovenous Fistula.

Arteriovenous fistula (AVF) is the most widely used hemodialysis vascular access in China. However, stenosis of the AVF limits its use. The mechanism of AVF stenosis is currently unknown. Therefore, the purpose of our study was to explore the mechanisms of AVF stenosis. In this study, we identified the differentially expressed genes (DEGs) based on the Gene Expression Omnibus (GEO) dataset (GSE39488) between venous segments of AVF and normal veins. A protein-protein interaction (PPI) network was constructed to identify hub genes of AVF stenosis. Finally, six hub genes (FOS, NR4A2, EGR2, CXCR4, ATF3, and SERPINE1) were found. Combined with the results of the PPI network analysis and literature search, FOS and NR4A2 were selected as the target genes for further investigation. We validated the bioinformatic results via reverse transcription PCR (RT-PCR) and Western blot analyses on human and rat samples. The expression levels of the mRNA and protein of FOS and NR4A2 were upregulated in both human and rat samples. In summary, we found that FOS may play an important role in AVF stenosis, which could be a potential therapeutic target of AVF stenosis.

Feasibility and safety of trans-biliary cryoablation: Preclinical evaluation of a novel flexible cryoprobe.

Cryoablation, as a well-characterized technology, has multifarious clinical applications in solid malignancy. However, trans-biliary cryoablation for malignant biliary obstruction has not been reported yet. Thus, this study aimed to determine the efficacy and safety of trans-biliary cryoablation with a novel CO2 gas-based flexible cryoprobe in standardized preclinical settings. For fresh porcine liver ex vivo, the freezing efficacy of cryoablation was evaluated by using fresh porcine liver. The real-time CO2 flow rate, freezing temperature and freezing range were examined and the frozen appearance was visualized. In vivo study, acute and chronical effects were investigated by using the models of canine bile duct. Histopathology and laboratory examination were performed. The lowest temperature that the electrode could deliver to the tissue was -60.7 °C. At 60s after freezing, the tissue temperature dropped to -22.6 °C and -4.3 °C at 0.1 and 0.2 cm from the electrode center, respectively. The frozen size was greater in liver tissue ex vivo than that in bile duct tissue in vivo. No biliary hemorrhage, perforation, stricture, obstruction, and adjacent organ injury were observed. With histopathologic examination, acute intercellular vacuoles were observed in the lamina propria adjacent to the lumen. Chronic changes, including uneven coagulative necrosis, fibro-proliferation, inflammatory infiltration and connective tissue thickening were observed in the lamina propria of the all biliary samples. The results demonstrated CO2 gas-based trans-biliary cryoablation is safe and efficacious. These findings may provide a potential new modality for primary malignant biliary obstruction and malignant obstruction within a biliary stent and contribute to cryoablation of clinical practice.

Comparative efficacy of five balloons for treating autogenous arteriovenous fistula stenosis: a Bayesian network meta-analysis.

BACKGROUND: Arteriovenous fistula (AVF) was the lifeline of patients with maintenance hemodialysis (MHD). However, stenosis of AVF may limit its use. Currently, AVF stenosis is commonly treated with balloon angioplasty. Meanwhile, several balloons were available. Therefore, this study aimed to explore the effectiveness of angioplasty with five different balloons in patients with AVF stenosis. METHODS: A network meta-analysis (NMA) was performed to synthesize direct and indirect evidence. We carried out a comprehensive literature search in PubMed, Embase, the Cochrane Central Register of Controlled Trials, Scopus, and ClinicalTrials.gov databases from database inception to January 31, 2021. The main outcomes were primary patency rates of AVF after 3, 6, 9, and 12 months. The NMA was performed using Stata 15 (network and mvmeta commands) and GeMTC software. RESULTS: Twenty randomized controlled trials (RCTs) involving 2,607 participants were included. Direct meta-analyses revealed no significant difference in primary patency rates between different balloons after 3, 6 and 9 months. However, NMA demonstrated that the effectiveness of plain balloon angioplasty (PBA) was inferior to that of the drug-coated balloon (DCB) after 3 and 9 months. Moreover, the results suggested that the high-pressure balloon (HPB) was inferior to DCB after 9 months. Thereafter, the analysis of the surface under the cumulative ranking curve (SUCRA) revealed that DCB was ranked as the first effective treatment after 3 months. The drug-eluting balloon (DEB) was the most effective treatment after 6, 9, and 12 months. The analyses revealed no significant publication bias. DISCUSSION: DEB may be the most effective treatment of AVF stenosis, followed by DCB. However, prospective studies involving large sample sizes of clinical trials and a direct comparison between DEB and DCB are required to clarify the individual value of different treatment options.

Role of ferroptosis-related molecular patterns in hepatocellular carcinoma microenvironment.

Heterogeneity and complexity of hepatocellular carcinoma (HCC) have been an impediment to effective diagnosis and treatment of HCC. Mounting evidence suggests that ferroptosis-related genes (FRGs) regulate the development of HCC by affecting the tumor microenvironment (TME). Herein, we explored the role of ferroptosis-related molecular patterns in the HCC microenvironment. The transcriptome and corresponding clinicopathological data of HCC patients were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, respectively. Molecular patterns of ferroptosis were explored using consensus clustering analysis and ferroptosis-related molecular patterns in the individual patients were analyzed using principal component analysis (PCA). The ability of ferroptosis-related patterns to predict the biological status and survival outcomes of HCC patients was investigated. Based on the expression of FRGs, three molecular patterns related to ferroptosis were identified. Single sample gene set enrichment analysis (ssGSEA) showed that the molecular patterns associated with the worst prognosis were significantly correlated with high infiltration of immunosuppressive cells in the TME. Besides, we identified three ferroptosis gene clusters underlying the different biological features of the three ferroptosis patterns. Patients in the high-risk group had a worse biological status and survival outcomes than those in the low-risk group. This study demonstrates that ferroptosis-related molecular patterns lead to high heterogeneity in HCC. These molecular patterns can be used to assess the survival of HCC patients and guide the design of immunotherapy strategies for HCC patients.

Efficacy of High-Pressure Balloon for the Treatment of Arteriovenous Fistula Stenosis: A Meta-Analysis.

OBJECTIVE: The objective of the present study was to compare the effectiveness of high-pressure balloon (HPB) versus conventional balloon (CB) angioplasty in treating arteriovenous fistula (AVF) stenosis. MATERIALS AND METHODS: A meta-analysis was conducted using data acquired from PubMed, EMBASE, the Cochrane Library, SinoMed, CNKI, WanFang, and VIP databases from the time the databases were established to December 2020. All analyses included in the studies comprised the subgroups of HPB and CB. The patency rates of AVF were compared between 2 groups at 3, 6, and 12 months after operation. RESULTS: Seven studies comprising 364 patients were included in the meta-analyses. The pooled results revealed that restenosis rate of AVFs treated with HPB was significantly lower than that of AVFs treated with CB at 3 months (odds ratio [OR] = 0.32, 95% confidence interval [CI] = 0.16 to 0.61, p<0.001) and 6 months after operation (OR= 0.29, 95% CI = 0.11 to 0.79, p = 0.01). In addition, the technical success rate of HPB groups was higher (OR = 0.13, 95% CI = 0.05 to 0.36, p<0.001). However, no significant difference was observed between HPB and CB groups at 12 months after operation (OR = 0.68, 95% CI = 0.30 to 1.52, p = 0.35). No significant publication bias was observed in the analyses. CONCLUSION: High-pressure balloon is a potential option for the treatment of AVF stenosis, with a lower 3- and 6-month restenosis rate than CB. However, 12-month patency rate of HPB was not superior to CB. Therefore, further studies should be conducted to investigate the mechanisms of restenosis after angioplasty.

Identification and validation of ferroptosis-associated gene-based on immune score as prognosis markers for hepatocellular carcinoma patients.

BACKGROUND: Ferroptosis has been found to affect the prognosis and immunotherapy of hepatocellular carcinoma (HCC). However, the association between ferroptosis-related genes and infiltrating immune cells in tumor immune microenvironment (TIME) has not been fully elucidated. This study aimed at establishing a prediction model for the progression of HCC using ferroptosis-associated genes based on immune score. METHODS: Transcriptomic, mutation and clinicopathological information were downloaded from TCGA and International Cancer Genome Consortium (ICGC) for this study. Construction of the prediction model was done by Lasso regression analysis. Estimation of the clustering ability of the prediction model was done by t-distributed stochastic neighbor embedding (t-SNE) and principal component analysis (PCA) analyses. Assessment of the accuracy of the prediction model was done by receiver operating characteristic (ROC) and Kaplan-Meier curves. RESULTS: A prediction model was formulated utilizing three ferroptosis-related genes (G6PD, SAT1 and SLC1A5). The model independently predicted the overall survival (OS). Differentially expressed genes (DEGs) linked to based on Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analyses immune-associated pathways and functions. Single-sample gene set enrichment analysis (ssGSEA) strategy further confirmed the model was related to immune-associated functions as well as immune cell infiltration. CONCLUSIONS: The three ferroptosis-associated gene-based prediction model was good at predicting the OS outcomes of HCC, improve HCC prognostication and treatment in the clinic.

Establishment of non-small-cell lung cancer risk prediction model based on prognosis-associated ADME genes.

PURPOSE: ADME genes are those involved in the absorption, distribution, metabolism, and excretion (ADME) of drugs. In the present study, a non-small-cell lung cancer (NSCLC) risk prediction model was established using prognosis-associated ADME genes, and the predictive performance of this model was evaluated and verified. In addition, multifaceted difference analysis was performed on groups with high and low risk scores. METHODS: An NSCLC sample transcriptome and clinical data were obtained from public databases. The prognosis-associated ADME genes were obtained by univariate Cox and lasso regression analyses to build a risk model. Tumor samples were divided into high-risk and low-risk score groups according to the risk score. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of the differentially expressed genes and the differences in the immune infiltration, mutation, and medication reactions in the two groups were studied in detail. RESULTS: A risk prediction model was established with seven prognosis-associated ADME genes. Its good predictive ability was confirmed by studies of the model's effectiveness. Univariate and multivariate Cox regression analyses showed that the model's risk score was an independent prognostic factor for patients with NSCLC. The study also showed that the risk score closely correlated with immune infiltration, mutations, and medication reactions. CONCLUSION: The risk prediction model established with seven ADME genes in the present study can predict the prognosis of patients with NSCLC. In addition, significant differences in immune infiltration, mutations, and therapeutic efficacy exist between the high- and low-risk score groups.

Construction of a prognostic model for non-small-cell lung cancer based on ferroptosis-related genes.

We wished to construct a prognostic model based on ferroptosis-related genes and to simultaneously evaluate the performance of the prognostic model and analyze differences between high-risk and low-risk groups at all levels. The gene-expression profiles and relevant clinical data of patients with non-small-cell lung cancer (NSCLC) were downloaded from public databases. Differentially expressed genes (DEGs) were obtained by analyzing differences between cancer tissues and paracancerous tissues, and common genes between DEGs and ferroptosis-related genes were identified as candidate ferroptosis-related genes. Next, a risk-score model was constructed using univariate Cox analysis and least absolute shrinkage and selection operator (Lasso) analysis. According to the median risk score, samples were divided into high-risk and low-risk groups, and a series of bioinformatics analyses were conducted to verify the predictive ability of the model. Single-sample gene set enrichment analysis (ssGSEA) was used to investigate differences in immune status between high-risk and low-risk groups, and differences in gene mutations between the two groups were investigated. A risk-score model was constructed based on 21 ferroptosis-related genes. A Kaplan-Meier curve and receiver operating characteristic curve showed that the model had good prediction ability. Univariate and multivariate Cox analyses revealed that ferroptosis-related genes associated with the prognosis may be used as independent prognostic factors for the overall survival time of NSCLC patients. The pathways enriched with DEGs in low-risk and high-risk groups were analyzed, and the enriched pathways were correlated significantly with immunosuppressive status.

Identification and validation of ADME genes as prognosis and therapy markers for hepatocellular carcinoma patients.

PURPOSE: ADME genes are genes involved in drug absorption, distribution, metabolism, and excretion (ADME). Previous studies report that expression levels of ADME-related genes correlate with prognosis of hepatocellular carcinoma (HCC) patients. However, the role of ADME gene expression on HCC prognosis has not been fully explored. The present study sought to construct a prediction model using ADME-related genes for prognosis of HCC. METHODS: Transcriptome and clinical data were retrieved from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC), which were used as training and validation cohorts, respectively. A prediction model was constructed using univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) analysis. Patients were divided into high- and low-risk groups based on the median risk score. The predictive ability of the risk signature was estimated through bioinformatics analyses. RESULTS: Six ADME-related genes (CYP2C9, ABCB6, ABCC5, ADH4, DHRS13, and SLCO2A1) were used to construct the prediction model with a good predictive ability. Univariate and multivariate Cox regression analyses showed the risk signature was an independent predictor of overall survival (OS). A single-sample gene set enrichment analysis (ssGSEA) strategy showed a significant relationship between risk signature and immune status. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed differentially expressed genes (DEGs) in the high- and low-risk groups were enriched in biological process (BP) associated with metabolic and cell cycle pathways. CONCLUSION: A prediction model was constructed using six ADME-related genes for prediction of HCC prognosis. This signature can be used to improve HCC diagnosis, treatment, and prognosis in clinical use.

Factors associated with dysfunction of autogenous arteriovenous fistula in patients with maintenance hemodialysis: a retrospective study.

BACKGROUND: Patients in maintenance hemodialysis (MHD) need a patent vascular access for optimal treatment. Autologous arteriovenous fistula (AVF) is the optimal vascular access for patients with MHD. However, AVF dysfunction may limit its use. The aim of this article is to explore the factors associated with primary dysfunction of AVF in patients with MHD. METHODS: This is a retrospective study. A total of 121 patients who underwent anastomosis for AVF in our hospital from January 1st, 2016 through December 31st, 2018 were screened for eligibility. Of these patients, 44 were excluded according to the exclusion criteria. The remaining patients were divided into two groups based on the function of vascular access. The complete blood count and other blood biochemical parameters were compared between two groups. The risk factors associated with AVF dysfunction were analyzed by multivariate Cox proportional hazard regression model for patients with end-stage renal disease (ESRD). RESULTS: There were significant differences in serum phosphorus (P), total cholesterol (TC), low density lipoprotein (LDL) and gender between patency and dysfunction groups of AVFs (P<0.05). Further multivariate COX proportional risk regression showed that hypercholesterolemia and hyperphosphatemia were independent risk factors for AVF dysfunction. CONCLUSIONS: Hypercholesterolemia and hyperphosphatemia are independent risk factors for primary AVF dysfunction in patients with MHD.

Characterization of diagnostic and prognostic significance of cell cycle-linked genes in hepatocellular carcinoma.

BACKGROUND: The high degree of heterogeneity of hepatocellular carcinoma (HCC) imposes a significant challenge to predict the prognosis. Currently, increasing evidence has indicated that cell cycle-linked genes are strongly linked to occurrence and progress of HCC. Herein, we purposed to create a prediction model on the basis of cell cycle-linked genes. METHODS: The transcriptome along with clinicopathological data abstracted from The Cancer Genome Atlas (TCGA) were used as a training cohort. Lasso regression analysis was employed to create a prediction model in TCGA cohort. The data of samples obtained from the International Cancer Genome Consortium (ICGC) data resource were applied in the verification of the model. A series of bioinformatics analyzed the relationship of the risk signature with overall survival (OS), biological function, and clinicopathological features. RESULTS: Six cell cycle-linked genes (PLK1, CDC20, HSP90AA1, CHEK1, HDAC1, and NDC80) were chosen to create the prognostic model, demonstrating a good prognostic capacity. Further analyses indicated that the model could independently assess the OS of HCC patients. A single-sample gene set enrichment analysis (ssGSEA) indicated that the risk signature was remarkably linked to immune status. Additionally, there was a remarkable association of the risk signature with TP53 mutation frequency, as well as immune checkpoint molecule expression levels. CONCLUSIONS: We created a prediction model using six cell cycle-linked genes to predict HCC prognosis. The six genes are expected to be novel markers for HCC diagnosis, as well as treatment.

Functions of CXC chemokines as biomarkers and potential therapeutic targets in the hepatocellular carcinoma microenvironment.

BACKGROUND: Several studies have indicated that CXC chemokines influence the prognosis and therapy in patients with hepatocellular carcinoma (HCC). However, there are limited studies on the roles of CXC chemokines in HCC based on data acquired from various databases. This study aimed to conduct an in-depth and comprehensive bioinformatic analysis of the expression and functions of CXC chemokines in HCC. METHODS: Data was obtained from various databases including ONCOMINE, UALCAN, STRING, GeneMinia, DAVID, Kaplan-Meier plotter, TIMER, GSCALite and NetworkAnalyst for the analysis of the expression and functions of the CXC chemokines in HCC. RESULTS: Analysis of the differential expression levels of CXC chemokines between HCC and adjacent normal tissues revealed that the mRNA expression levels of CXCL1/2/5/6/7/12/14 were significantly lower in HCC tissues than those in adjacent normal tissues, whereas the mRNA expression levels of CXCL9/16/17 were significantly higher in HCC tissues. Analysis of the relationship between CXC chemokines and overall survival revealed that high mRNA expression levels of CXCL1/3/5/6/8 were associated with poor overall survival, whereas high mRNA expression levels of CXCL2/4/7/9/10/12 were associated with better overall survival. The functions of CXC chemokines and related genes were associated with cytokine-cytokine receptor interactions and chemokine signaling pathway. Analysis of the association between CXC chemokines and activity of cancer pathways indicated that the DNA damage response and hormone androgen receptor (AR) signaling pathways were inhibited, whereas apoptosis, epithelial-mesenchymal transition (EMT) and Ras/mitogen-activated protein kinase (MAPK) signaling pathways were activated. The expression of CXC chemokines was positively correlated with the infiltration of six types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells). CONCLUSIONS: This study has demonstrated that CXC chemokines can influence survival of patients with HCC by recruiting different types of immune cells into the tumor microenvironment.

A hypoxia-linked gene signature for prognosis prediction and evaluating the immune microenvironment in patients with hepatocellular carcinoma.

BACKGROUND: Previous research indicates that hypoxia critically affects the initiation and progression of hepatocellular carcinoma (HCC). Nevertheless, the molecular mechanisms responsible for HCC development are poorly understood. Herein, we purposed to build a prognostic model using hypoxia-linked genes to predict patient prognosis and investigate the relationship of hypoxia with immune status in the tumor microenvironment (TME). METHODS: The training cohort included transcriptome along with clinical data abstracted from The Cancer Genome Atlas (TCGA). The validation cohort was abstracted from Gene Expression Omnibus (GEO). Univariate along with multivariate Cox regression were adopted to create the prediction model. We divided all patients into low- and high-risk groups using median risk scores. The estimation power of the prediction model was determined with bioinformatic tools. RESULTS: Six hypoxia-linked genes, HMOX1, TKTL1, TPI1, ENO2, LDHA, and SLC2A1, were employed to create an estimation model. Kaplan-Meier, ROC curve, and risk plot analyses demonstrated that the estimation potential of the risk model was satisfactory. Univariate along with multivariate regression data illustrated that the risk model could independently predict the overall survival (OS). A nomogram integrating the risk signature and clinicopathological characteristics showed a good potential to estimate HCC prognosis. Gene set enrichment analysis (GSEA) revealed that genes associated with cell proliferation and metabolism cascades were abundant in high-risk group. Furthermore, the signature showed a strong ability to distinguish the two groups in terms of immune status. CONCLUSIONS: A prediction model for predicting HCC prognosis using six hypoxia-linked genes was designed in this study, facilitating the diagnosis and treatment of HCC.

Phenotypic Switching of Atherosclerotic Smooth Muscle Cells is Regulated by Activated PARP1-Dependent TET1 Expression.

AIM: During the development of atherosclerosis, the vascular smooth muscle cells (SMCs) undergo phenotypic switching from contractile phenotype to synthetic phenotype. This study aimed at examining the role of DNA modification mediated by the oxidative stress dependent ten eleven translocation enzymes (TETs) expression at early stage of phenotypic switching. METHODS: Based on the in vitro SMCs calcification model, DNA damage, phenotypic switching and 5-hydroxymethylcytosine (5hmC) were examined by comet assay, alkaline DNA unwinding assay, immunofluorescence staining, Dot blotting and Western blotting. Then Western blotting and qRT-PCR were performed to analyze the TETs expression and the relationship between the activity of poly(ADP-ribose) polymerase 1 (PARP1) and TETs expression. We further alter 5hmC modification by inhibition of TET1 or PARP1 to rescue the phenotypic switching of SMCs using immunofluorescence staining, Dot blotting and qRT-PCR. We performed immunochemistry staining to examine the activated PARP1-TET1 pathway in vivo. RESULTS: The phenotypic switching was observed in the SMCs cultured with calcification medium as the expression of the cell markers of contractile SMCs decreased and cell proliferation increased. In contrast, PAR and 5hmC were markedly increased in SMCs with calcification due to DNA damage. Our study further demonstrated that oxidative stress-activated PARP1, promotes TET1 expression and 5hmC increase during the phenotypic switching. Inhibition of TET1 or PARP1 can rescue the phenotypic switching of SMCs with calcification. CONCLUSION: Our study demonstrated the important role of PARylation dependent 5hmC, in SMCs phenotypic switching. It raises the possibility to target TET1 and PARP1 for atherosclerosis treatment.

A Prognostic Nomogram Based on Immune Scores Predicts Postoperative Survival for Patients with Hepatocellular Carcinoma.

BACKGROUND: Increasing research attention has focused on tumor-infiltrating immune cells. However, the threshold of an immune score for use in predicting overall survival (OS) and disease-free survival (DFS) in hepatocellular carcinoma (HCC) is not defined. This study aims at exploring the association between immune scores with prognosis and building a clinical nomogram for predicting the survival of HCC patients. Material and Methods. A total of 299 patients were enrolled in this study. Their clinical pathological characteristics and immune scores downloaded from The Cancer Genome Atlas (TCGA) database were analyzed. Survival differences between different immune score subgroups were compared, and a final nomogram was built using the Cox proportional hazards regression model. The predictive performance of the nomogram was assessed using the concordance index (C-index) and a calibration plot. RESULTS: All the patients were divided into three subgroups based on immune scores. Patients with medium and high immune scores had significantly better OS (HR and 95% CI: 0.417 [0.186-0.937] and 0.299 [0.146-0.616]) and DFS (HR and 95% CI: 0.575 [0.329-1.004] and 0.451 [0.278-0.733], respectively, compared with those with low immune scores. The C indices for OS and DFS were 0.748 (95% CI, 0.687-0.809) and 0.675 (95% CI, 0.630-0.720), respectively. A calibration plot used to determine the probability of survival at 3 or 5 years (OS and DFS) showed a significant agreement between nomogram predictions and actual observations. CONCLUSIONS: Medium and high immune scores are significantly associated with prolonged OS and DFS in HCC patients. Nomograms built in this study can help doctors and patients assess prognosis and guide treatment.

Preoperative serum apolipoprotein A-I levels predict long-term survival in non-muscle-invasive bladder cancer patients.

INTRODUCTION: The aim of this study was to elucidate the association between apolipoprotein A-I (Apo A-I) and overall survival (OS) as well as cancer-specific survival (CSS) in non-muscle-invasive bladder cancer (NMIBC) patients undergoing transurethral resection of bladder tumor (TURBT). PATIENTS AND METHODS: We retrospectively collected data of 470 eligible patients diagnosed with NMIBC and who received TURBT between January 2004 and December 2011. Pretreatment blood indexes were examined. The association of Apo A-I with clinicopathological characteristics was further analyzed by dichotomizing our sample into those with Apo A-I ≤ 1.19 g/L (low Apo A-I group) and those with Apo A-I > 1.19 g/L (high Apo A-I group). OS and CSS were estimated by Kaplan-Meier analysis and the log-rank test was used to compare differences between groups. Univariate and multivariate Cox regression analyses were plotted to assess the prognostic value of Apo A-I in NMIBC patients. In addition, subgroup analyses were performed according to the risk classification of the International Bladder Cancer Group. RESULTS: In the overall population, patients in the high Apo A-I group had greater 5-year OS and 5-year CSS rates as compared to those in the low Apo A-I group. Kaplan-Meier survival analysis revealed that higher albumin, Apo A-I, and hemoglobin levels were associated with greater OS and CSS while elevated neutrophil-lymphocyte ratio was associated with worse OS and CSS in the overall and high-risk population rather than low- and intermediate-risk population. Furthermore, Apo A-I was shown to be an independent predictor in the overall population (for OS, hazard ratio [HR], 0.364, 95% confidence interval [CI], 0.221-0.598, p < 0.001; for CSS, HR, 0.328, 95% CI, 0.185-0.583, p < 0.001) and high-risk patients (for OS, HR, 0.232, 95% CI 0.121-0.443, p < 0.001; for CSS, HR, 0.269, 95% CI, 0.133-0.541, p < 0.001). CONCLUSION: These results suggest that Apo A-I level could potentially serve as a useful prognostic indicator for therapeutic decision making in NMIBC patients.