Unveiling a cuproptosis-related risk model and the role of FARSB in hepatocellular carcinoma.

Background: Cuproptosis, a type of regulated cell death that was recently identified, has been linked to the development of a variety of diseases, among them being cancers. Nevertheless, the prognostic significance and therapeutic implications of the cuproptosis potential index in hepatocellular carcinoma (HCC) remain uncertain. Methods: Single-sample gene set enrichment analysis (ssGSEA) and Weighted Gene Co-expression Network Analysis (WGCNA) methodology was conducted to ascertain the identification of modular genes that are closely linked to cuproptosis. In addition, the gene signature indicative of prognosis was formulated by employing univariate Cox regression analysis in conjunction with a random forest algorithm. The efficacy of this gene signature in predicting outcomes was confirmed through validation in both The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. Furthermore, a study was undertaken to evaluate the association between the risk score and various clinical-pathological characteristics, explore the biological processes linked to the gene signature, and analyze tumor mutational burden and somatic mutations. Lastly, potential drugs targeting the identified gene signature were identified through screening. Results: The results of our comprehensive analysis across multiple cancer types demonstrated a positive correlation between an elevated cuproptosis potential index (CPI) and an accelerated rate of tumor progression. Furthermore, employing the WGCNA technique, we successfully identified 640 genes associated with cuproptosis. Among these genes, we meticulously screened and validated a seven-gene signature (TCOF1, NOP58, TMEM69, FARSB, DHX37, SLC16A3, and CBX2) that exhibited substantial prognostic significance. Using the median risk score, the division of HCC patients into cohorts with high- and low-risk highlighted significant disparities in survival results, wherein the group with higher risk exhibited a less favorable overall survival. The risk score exhibited commendable predictive efficacy. Moreover, the in vitro knockdown of FARSB significantly hindered cell viability, induced G1 phase arrest, increased apoptosis, and impaired migration in HepG2 and Huh7 cells. Conclusion: Our research has successfully identified a strong seven-gene signature linked to cuproptosis, which could be utilized for prognostic evaluation and risk stratification in patients with HCC. Furthermore, the discovered gene signature, coupled with the functional analysis of FARSB, presents promising prospects as potential targets for therapeutic interventions in HCC.

Prognostic Comparison between cTACE and H101-TACE in Unresectable Hepatocellular Carcinoma (HCC): A Propensity-Score Matching Analysis.

Background: Transarterial chemoembolization (TACE) is the most common treatment for patients with HCC who are unsuitable for radical therapies. Conventional TACE (cTACE) takes advantage of the preferential hepatic arterial supply of HCC for the targeted delivery of chemotherapeutic agents suspended in lipiodol, followed by embolization or reduction of arterial flow using various types of particles while sparing the surrounding liver parenchyma. Aims and Objectives. The current study is aimed at comparing the efficacy and safety profiles of transarterial infusion of recombinant human type-5 adenovirus (H101-TACE) with conventional transarterial chemoembolization (cTACE) in patients with unresectable hepatocellular carcinoma (HCC). Methods: Unresectable HCC patients that received H101-based TACE or cTACE from August 2018 to September 2021 were retrospectively evaluated. Propensity score matching (PSM) has a 1 : 1 ratio to eliminate possible confounder imbalances across cohorts. The main outcome was overall survival (OS), while secondary outcomes were progression-free survival (PFS) and tumor response. Results: This study included 111 patients classified across two cohorts: the H101-TACE cohort (n = 37) and the cTACE cohort (n = 74). Median OS within the H101-TACE cohort was 9.0 months longer than within the cTACE cohort before PSM (22.1 vs. 13.1 months, P = 0.043) and 9.3 months longer following PSM (22.1 vs. 12.8 months, P = 0.004). The median PFS within the H101-TACE cohort was 3.2 months longer compared to the cTACE cohort before PSM (6.5 vs. 3.3 months, P = 0.046) and 2.5 months after PSM (6.5 vs. 4.0 months, P = 0.012). The disease control rate for H101 and control cohorts was 81.1% and 59.5%, accordingly (P = 0.039). Conclusion: The present study demonstrated that the H101-TACE is safe and efficient and can considerably enhance prognostic results for unresectable HCC compared to cTACE.

[Angiodynamic and optical coupling analysis of skin tissue model under finite pressure].

The pulse amplitude of fingertip volume could be improved by selecting the vascular dense area and applying appropriate pressure above it. In view of this phenomenon, this paper used Comsol Multiphysics 5.6 (Comsol, Sweden), the finite element analysis software of multi-physical field coupling simulation, to establish the vascular tissue model of a single small artery in fingertips for simulation. Three dimensional Navier-Stokes equations were solved by finite element method, the velocity field and pressure distribution of blood were calculated, and the deformation of blood vessels and surrounding tissues was analyzed. Based on Lambert Beer's Law, the influence of the longitudinal compression displacement of the lateral light surface region and the tissue model on the light intensity signal is investigated. The results show that the light intensity signal amplitude could be increased and its peak value could be reduced by selecting the area with dense blood vessels. Applying deep pressure to the tissue increased the amplitude and peak of the signal. It is expected that the simulation results combined with the previous experimental experience could provide a feasible scheme for improving the quality of finger volume pulse signal.

The Prognostic Significance and Potential Mechanism of Ferroptosis-Related Genes in Hepatocellular Carcinoma.

Ferroptosis exerts a pivotal role in the formation and dissemination processes of hepatocellular carcinoma (HCC). The heterogeneity of ferroptosis and the link between ferroptosis and immune responses have remained elusive. Based on ferroptosis-related genes (FRGs) and HCC patients from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) cohorts, we comprehensively explored the heterogeneous ferroptosis subtypes. The genetic alterations, consensus clustering and survival analysis, immune infiltration, pathway enrichment analysis, integrated signature development, and nomogram building were further investigated. Kaplan-Meier plotter confirmed statistically differential probabilities of survival among the three subclusters. Immune infiltration analysis showed there were clear differences among the types of immune cell infiltration, the expression of PD-L1, and the distribution of TP53 mutations among the three clusters. Univariate Cox regression analysis, random survival forest, and multivariate Cox analysis were used to identify the prognostic integrated signature, including MED8, PIGU, PPM1G, RAN, and SNRPB. Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) curves revealed the satisfactory predictive potential of the five-gene model. Subsequently, a nomogram was established, which combined the signature with clinical factors. The nomogram including the ferroptosis-based signature was conducted and showed some clinical net benefits. These results facilitated an understanding of ferroptosis and immune responses for HCC.

The effect of different drugs on hard metal lung disease in a rat model.

Hard metal lung disease (HMLD) drugs include dexamethasone sodium phosphate (Dex), methylprednisolone (MP) injection, N-acetylcysteine injection (NAC), and a mix of Dex, MP, and NAC (MIX). In this study, we compared the effects of these drugs on different cytokines of hard metal lung disease in a rat model. Thirty-six adult female Sprague Dawley rats were distributed equally into the control group, hard metal (HM) group, Dex group, MP group, NAC group, and MIX group. HM powder (0.5 mL, 20 mg/mL; one time) was administered by intraperitoneal injection to the HM group through the pulmonary endotracheal tube, while the control group received normal saline (0.5 mL, 20 mg/mL; one time). After 4 weeks, the drugs were administered to the experimental groups (0.5 mL, 20 mg/mL; one time). After 8 weeks, bronchoalveolar lavage fluid (BALF) and serum were examined for cytokine levels. Biochemical analysis indicated that the Dex, MP, NAC, and MIX did not improve TGF-ß1, TGF-ß2, KL-6, and MMP-1 in the BALF, while MIX increased TIMP-1 in BALF. In addition, the NAC treatment significantly increased the expression levels of TGF-ß1, TGF-ß2, KL-6, and MMP-1. The MIX treatment significantly increased the expression levels of TGF-ß1, TGF-ß2, and KL-6. The MP treatment significantly increased the expression levels of KL-6, and MMP-1. The Dex treatment significantly increased the expression levels of TGF-ß1, KL-6, and MMP-1. This study demonstrated that administered with NAC and MIX could improve TGF-ß1, TGF-ß2, and KL-6 in serum of hard metal lung disease in a rat model. Therefore, NAC injection may be considered a useful candidate in the development of a preventive agent against HMLD.

Impact of treatment-duration-ratio of traditional Chinese medicine on survival period of primary liver cancer -A real-world study.

Introduction: In China, traditional Chinese medicine (TCM) is regarded as an effective treatment for primary liver cancer (PLC). The present study analyzed the effect of TCM on the survival period of patients with PLC by analyzing the relationship between the treatment-duration-ratio of traditional Chinese medicine (C-TDR, (traditional Chinese medicine treatment duration)/(Overall treatment duration) × 100%) and the survival time of 1002 patients with PLC. Methods: In this study, 1002 patients with PLC admitted to TCM Oncology Department of Changhai Hospital from January, 2015 to December, 2019 were enrolled. The univariate and multivariate Cox regression equation, propensity score matching (PSM) were performed to identify independent prognostic factors for survival outcomes of PLC patients at different stages and estimate the influence of C-TDR on survival time. Results: Cox regression analysis indicated that C-TDR was an independent prognostic factor for survival outcome (P＜0.05) and a corresponding reduction of relative risk of death of 75.67% (relative risk (RR) = 0.2433; 95%Confedential Interval (CI) = 0.1747-0.3388). Similarly, it is also an independent prognostic factor for patients outcome of each stage (P＜0.05). The 251 patients of BCLC-A reduced 96.09% risk of mortality (RR = 0.0391; 95%CI = 0.0151-0.1012). The 396 BCLC-B patients decreased risk of death of 81.24% (RR = 0.1876, 95%CI = 0.1112-0.3163). Moreover, 355 patients of stage C demonstrated a 51.36% lower risk of death (RR = 1.0016, 95%CI = 0.9885-1.0149). Significant differences were found in the median overall survival (OS) both higher and lower C-TDR of all patients. Even after PSM, the overall survival of two groups were significantly improved following each stage. Conclusion: Earlier administration of traditional Chinese medicine can reduce the risk of mortality and prolong survival in patients with liver cancer.

Relationship between thick or greasy tongue-coating microbiota and tongue diagnosis in patients with primary liver cancer.

Tongue diagnosis is a unique aspect of traditional Chinese medicine for diagnosing diseases before determining proper means of treatment, but it also has the disadvantage of relying on the subjective experience of medical practitioners and lack objective basis. The purpose of this article is to elucidate tongue-coating microbiota and metabolic differences in primary liver cancer (PLC) patients with thick or greasy tongue coatings. Tongue-coating samples were analyzed in 60 PLC patients (30 PLC with thick or greasy tongue-coating patients and 30 PLC with tongue-coating neither thick nor greasy) and 25 healthy controls (HC) using 16S rRNA gene sequencing technology. As compared to healthy individuals, tongue coatings of patients with PLC had elevated levels of Firmicutes and Actinobacteria. The abundance of Fusobacteria, SR1_Absconditabacteria_, and Spirochaete were higher in tongue coatings of healthy controls compared to samples in patients with PLC. In addition to site-specific differences, higher abundances of Fusobacteria and Actinobacteria were observed in thick or greasy tongue-coating patients as compared to non-thick and greasy tongue-coating patients. The inferred metagenomic pathways enriched in the PLC tongue-coating patients were mainly those involved in replication, recombination, and repair of protein. We also identify a tongue-coating microbiome signature to discriminate HC and PLC, including 15 variables on genus level. The prediction performance of the signature showed well in the training and validation cohorts. This research illustrates specific clinical features and bacterial structures in PLC patients with different tongue coatings, which facilitates understanding of the traditional tongue diagnosis.

m6A RNA Methylation Regulators Elicit Malignant Progression and Predict Clinical Outcome in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and N6-methyladenosine (m6A) is a predominant internal modification of RNA in various cancers. We obtained the expression profiles of m6A-related genes for HCC patients from the International Cancer Genome Consortium and The Cancer Genome Atlas datasets. Most of the m6A RNA methylation regulators were confirmed to be differentially expressed among groups stratified by clinical characteristics and tissues. The clinical factors (including stage, grade, and gender) were correlated with the two subgroups (cluster 1/2). We identified an m6A RNA methylation regulator-based signature (including METTL3, YTHDC2, and YTHDF2) that could effectively stratify a high-risk subset of these patients by univariate and LASSO Cox regression, and receiver operating characteristic (ROC) analysis indicated that the signature had a powerful predictive ability. Immune cell analysis revealed that the genes in the signature were correlated with B cell, CD4 T cell, CD8 T cell, dendritic cell, macrophage, and neutrophil. Functional enrichment analysis suggested that these three genes may be involved in genetic and epigenetic events with known links to HCC. Moreover, the nomogram was established based on the signature integrated with clinicopathological features. The calibration curve and the area under ROC also demonstrated the good performance of the nomogram in predicting 3- and 5-year OS in the ICGC and TCGA cohorts. In summary, we demonstrated the vital role of m6A RNA methylation regulators in the initial presentation and progression of HCC and constructed a nomogram which would predict the clinical outcome and provide a basis for individualized therapy.

Sec62 promotes pro-angiogenesis of hepatocellular carcinoma cells under hypoxia.

This study aimed to investigate the underlying molecular pathogenic mechanism of Sec62 in hepatocellular carcinoma (HCC). Microarray analysis was conducted to profile the global gene expression in the HCC cell line Huh7 cells transfected with Sec62high vs. NC and Sec62low vs. NC. Ingenuity pathway analysis and gene set enrichment analysis were used to perform Sec62-related signaling pathway analysis from screened differentially expressed genes (DEGs). A protein-protein interaction network was constructed. Experimental validation of the expression of key DEGs was conducted. Hypoxia-induced tube formation was undertaken to investigate the role of Sec62 in angiogenesis. A total of 74 intersected DEGs were identified from Huh7 cells with Sec62high vs. NC and Sec62low vs. NC. Among them, 65 DEGs were correlated with the expression of Sec62. The P53 signaling pathway was found to be enriched in Huh7 cells with Sec62high vs. NC, while the acute phase response signaling pathway was enriched in Huh7 cells with Sec62low vs. NC. DEGs, such as serine protease inhibitor E (SERPINE) and tumor necrosis factor receptor superfamily, member 11B (TNFRSF11B), were not only identified as the lead genes of these enriched pathways, but were also found to be closely related to Sec62. Moreover, knockdown of Sec62 decreased the expression of SERPINE1 (plasminogen activator inhibitor type 1 (PAI-1)) and TNFRSF11B, whereas overexpression of Sec62 had the opposite effects. In addition, knockdown of Sec62 inhibited hypoxia-induced tube formation via PAI-1. Sec62 promoted pro-angiogenesis of HCC under hypoxia by regulating PAI-1, and it may be a crucial angiogenic switch in HCC.

Prognostic Power of a Chaperonin Containing TCP-1 Subunit Genes Panel for Hepatocellular Carcinoma.

Chaperonin containing TCP-1 (T-complex protein 1) (CCT) is a large molecular weight complex that contains nine subunits (TCP1, CCT2, CCT3, CCT4, CCT5, CCT6A, CCT6B, CCT7, CCT8). This study aimed to reveal key genes which encode CCT subunits for prognosis and establish prognostic gene signatures based on CCT subunit genes. The data was downloaded from The Cancer Genome Atlas, International Cancer Genome Consortium and Gene Expression Omnibus. CCT subunit gene expression levels between tumor and normal tissues were compared. Corresponding Kaplan-Meier analysis displayed a distinct separation in the overall survival of CCT subunit genes. Correlation analysis, protein-protein interaction network, Gene Ontology analysis, immune cells infiltration analysis, and transcription factor network were performed. A nomogram was constructed for the prediction of prognosis. Based on multivariate Cox regression analysis and shrinkage and selection method for linear regression model, a three-gene signature comprising CCT4, CCT6A, and CCT6B was constructed in the training set and significantly associated with prognosis as an independent prognostic factor. The prognostic value of the signature was then validated in the validation and testing set. Nomogram including the signature showed some clinical benefit for overall survival prediction. In all, we built a novel three-gene signature and nomogram from CCT subunit genes to predict the prognosis of hepatocellular carcinoma, which may support the medical decision for HCC therapy.

Comparable effects of Jiedu Granule, a compound Chinese herbal medicine, and sorafenib for advanced hepatocellular carcinoma: A prospective multicenter cohort study.

OBJECTIVE: Sorafenib has been extensively used for the treatment of advanced hepatocellular carcinoma (HCC), and Chinese herbal medicine has also been used to manage advanced HCC. The present work evaluates the effectiveness and safety of Jiedu (JD) Granule, a compound of traditional Chinese herbal medicine, side-by-side with sorafenib for the treatment of advance HCC. METHODS: Patients with advanced HCC receiving treatment with JD Granule or sorafenib were enrolled from December 2014 to March 2018. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and safety. Propensity score matching (PSM) analysis was used to control for possible selection bias from the study group allocation process. RESULTS: Of the 325 patients included, 161 received JD Granule and 164 received sorafenib. No significant differences were found in OS or PFS among patients receiving JD Granule compared to sorafenib (P > 0.05). Median OS of the two study groups was 6.83 months (95% confidence interval [CI]: 5.83-9.47) in the group receiving JD Granule and 8 months (95% CI: 6.67-9.80) in the group receiving sorafenib, with half-, 1- and 2-year survival rates of 53.6%, 31.2% and 13.2% vs 60.1%, 35.5% and 14.2%, respectively. Even after PSM, the median survival time did not differ between the JD Granule group (9.03 months; 95% CI: 6.37-14.2) and the sorafenib group (7.93 months; 95% CI: 6.5-9.97), with comparable half-, 1- and 2-year survival rates. The most common adverse events (AEs) were diarrhea (13.7%) and fatigue (5.6%) in the JD Granule group, and hand-foot skin reaction (46.3%) and diarrhea (36.6%) in the sorafenib group. The JD Granule was more cost-effective than sorafenib treatment for advanced HCC. CONCLUSION: Compared to sorafenib, JD Granule was more cost-effective and caused fewer AEs for the treatment of Chinese patients with advanced HCC.

Identification of a nomogram based on long non-coding RNA to improve prognosis prediction of esophageal squamous cell carcinoma.

PURPOSE: Esophageal squamous cell carcinoma (ESCC) remains a common aggressive malignancy in the world. Several long non-coding RNAs (lncRNAs) are reported to predict the prognosis of ESCC. Therefore, an in-depth research is urgently needed to further investigate the prognostic value of lncRNAs in ESCC. RESULTS: From the training set, we identified a eight-lncRNA signature (including AP000487, AC011997, LINC01592, LINC01497, LINC01711, FENDRR, AC087045, AC137770) which separated the patients into two groups with significantly different overall survival (hazard ratio, HR = 3.79, 95% confidence interval, 95% CI [2.56-5.62]; P < 0.001). The signature was applied to the validation set (HR = 2.73, 95%CI [1.65-4.53]; P < 0.001) and showed similar prognostic values. Stratified, univariate and multivariate Cox regression analysis indicated that the signature was an independent prognostic factor for patients with ESCC. A nomogram based on the lncRNAs signature, age, grade and stage was developed and showed good accuracy for predicting 1-, 3- and 5-year survival probability of ESCC patients. We found a strong correlation between the gene significance for the survival time and T stage. Eight modules were constructed, among which the key module most closely associated with clinical information was identified. CONCLUSIONS: Our eight-lincRNA signature and nomogram could be practical and reliable prognostic tools for esophageal squamous cell carcinoma. METHODS: We downloaded the lncRNA expression profiles of ESCC patients from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets and separated to training and validation cohort. The univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were used to identify a lncRNA-based signature. The predictive value of the signature was assessed using the Kaplan-Meier method, receiver operating characteristic (ROC) curves and area under curve (AUC). Weighted gene co-expression network analysis (WGCNA) was applied to predict the intrinsic relationship between gene expressions. In addition, we further explored the combination of clinical information and module construction.

CFHR3 is a potential novel biomarker for hepatocellular carcinoma.

Complement factor H-related 3 (CFHR3) is a protein-coding gene acting in various diseases. However, its prognostic values of CFHR3 in hepatocellular carcinoma (HCC) are not understandable. Therefore, we present a further study on CFHR3 in HCC. CFHR3 expression data were acquired from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). We compared the differential expression of CFHR3 between the low-stage (stage I and II) and high-stage (stage III and IV) patients with HCC in the TCGA and ICGC cohorts. Furthermore, we assessed the CFHR3 expression as a prognostic marker using the Kaplan-Meier survival analysis, univariate, and multivariate analysis. The Kaplan-Meier analysis declared that CFHR3 overexpression was correlated with a good prognosis for HCC patients. Multivariate analysis proved the prognostic significance of CFHR3 expression levels (P < .001 and .003 for TCGA and ICGC, respectively). Immune-related scores in low-risk cohorts were higher than high-risk cohorts. Gene set enrichment analysis implied that the low CFHR3 expression phenotype was significantly enriched in critical biological functions and pathways and was associated with tumorigenesis, such as regulation of cell activation cycle, and the WNT and NOTCH signal pathway. Above all, CFHR3 could be a novel prognostic biomarker and therapeutic target for HCC.

Sec62 promotes early recurrence of hepatocellular carcinoma through activating integrinα/CAV1 signalling.

Postsurgical recurrence within 2 years is the major cause of poor survival of hepatocellular carcinoma (HCC) patients. However, the molecular mechanism underlying HCC recurrence remains unclear. Here, we distinguish the function and mechanism of Sec62 in promoting HCC recurrence. The correlation between Sec62 and early recurrence was demonstrated in 60 HCC samples from a prospective study. HCC cells with Sec62 knockdown (Sec62KD) or overexpression (Sec62OE) were used to determine the potential of Sec62 in cell migration in vitro. Microarray analysis comparing Sec62KD or Sec62OE to their control counterparts was used to explore the mechanisms of Sec62-induced recurrence. A luciferase-labelled orthotopic nude mouse model of HCC with Sec62KD or Sec62OE was used to validate the potential of Sec62 in early HCC recurrence in vivo. We found that high expression of Sec62 was positively correlated with surgical recurrence in clinical HCC samples. Multivariate analysis revealed that Sec62 was an independent prognostic factor for early recurrence in postoperative HCC patients. Moreover, Sec62 promoted migration and invasion of HCC cells in vitro and postsurgical recurrence in vivo. Mechanically, integrinα/CAV1 signalling was identified as one of the targets of Sec62 in cell movement. Overexpression of integrin α partially rescued the Sec62 knockdown-induced inhibition of cell migration. Sec62 is a potentially prognostic factor for early recurrence in postoperative HCC patients and promotes HCC metastasis through integrinα/CAV1 signalling. Sec62 might be an attractive drug target for combating HCC postsurgical recurrence.

Identification of a RNA-seq-based signature to improve prognostics for uterine sarcoma.

OBJECTIVE: Uterine sarcoma (US) is a highly malignant cancer with poor prognosis and high mortality. This study focused on the identification of a RNA-Seq expression signature for prognosis prediction in uterine sarcoma. METHODS: We obtained RNA-Seq expression profiles from The Cancer Genome Atlas database, and differentially expressed genes were identified between US tissues and normal tissues. Univariate Cox proportional hazards regression analysis and LASSO Cox model were performed to identify and construct the prognostic gene signature. Time-dependent receiver operating characteristic, Kaplan-Meier curve and multivariate Cox regression analysis were used to assess the prognostic capacity of the six-gene signature. The nomogram was developed including prognostic signature and independent clinical factors to predict the overall survival (OS) of US patients. The functional enrichment and somatic mutation analysis were also analyzed by bioinformatics to understand the molecular mechanisms. RESULTS: This study identified a prognostic signature based on 6 genes: FGF23, TLX2, TIFAB, RNF223, HIST1H3A and AADACL4. In the training group, the median OS in the high- and low-risk groups was 19.6 vs 88.1 months (HR, 0.1412, 95% CI: 0.03295 - 0.6054; P = 0.002), respectively. In the testing group, the median OS in the high- and low-risk groups were 30 vs NR (not reach) months (HR, <0.0001, 95% CI: 0 - inf; P = 0.03). In all of patients, the low-risk group showed significant better survival compared with the high-risk group in OS, PFI, DSS and DFI. The nomogram based on the gene signature and radiation therapy was developed and successfully predicted the OS of US patients. The patients in the high-risk group displayed distinct mutation signatures comparing to patients in the low-risk group. Functional enrichment analysis indicated that the signature can play a vital role in cancer-related biological processes. CONCLUSION: Our study established a novel 6-gene signature and nomogram which could improve prognosis prediction in patients with US.

Prognostic Role of Platelet-to-Lymphocyte Ratio in Hepatocellular Carcinoma with Different BCLC Stages: A Systematic Review and Meta-Analysis.

The role of platelet-to-lymphocyte ratio (PLR) in the prognosis of hepatocellular carcinoma (HCC) patients with different Barcelona Clinic Liver Cancer (BCLC) stages remains controversial. This systematic review and meta-analysis aimed to determine the efficacy of PLR on HCC prognosis. Five electronic databases were searched for clinical trials focusing on the role of PLR in the prognosis of HCC. A total of 297 potential studies were initially identified, and 9 studies comprising 2449 patients were finally enrolled to evaluate the association between the pretreatment PLR and clinical outcomes of overall survival (OS), disease-free survival (DFS), and event occurrence in patients with HCC in different BCLC stages. An elevated pretreatment PLR indicated unfavorable worse OS (HR = 1.73; 95% CI: (1.46, 2.04); P < 0.00001) and DFS (HR = 1.30; 95% CI: (1.06, 1.60); P = 0.01). Subgroup analysis indicated that high PLR indicated poor OS among BCLC-B/C patients without heterogeneity, while PLR in BCLC-A patients indicated high statistical heterogeneity with I2 value of 78%. As for the correlation between PLR and event occurrence, high PLR was related to poor clinical event occurrence only among BCLC-C patients, though obvious heterogeneity was observed in all different BCLC stages. In conclusion, PLR may be a significant biomarker in the prognosis of HCC in different BCLC stages.

Transarterial chemoembolization combined with Jie-du granule preparation improves the survival outcomes of patients with unresectable hepatocellular carcinoma.

The aim of the present study was to compare the effectiveness of transarterial chemoembolization (TACE), TACE combined with Jie-du granules (JD), and TACE combined with sorafenib (SOR) for treating patients with unresectable hepatocellular carcinoma (HCC). For this purpose, we conducted a retrospective analysis of data from 266 consecutive patients with unresectable HCC who underwent TACE treatment at the Shanghai Hospital and Eastern Hepatic Surgery Hospital between Jan 2009 and Dec 2010. We prospectively analyzed patient survival and progression times as well as independent predictors, within a follow-up period of 86 months. Patients were divided into TACE-JD (n = 75), TACE-SOR (n = 124) and TACE (n = 67) groups. Median overall survival (OS) times being: TACE-JD, 21.43 months; TACE-SOR, 23.23 months; TACE, 13.97 months (TACE-SOR vs TACE, P < 0.001; TACE-SOR vs TACE-JD, P = 0.852; TACE-JD vs TACE, P < 0.001). The median times to progression (TTP) were as follows: TACE-JD, 8.67 months; TACE-SOR, 5.37 months; TACE, 4.57 months (TACE-SOR vs TACE, P = 0.479; TACE-SOR vs TACE-JD, P < 0.001; TACE-JD vs TACE, P < 0.001). Independent predictors of OS were treatment allocation, Child-Pugh class large tumor, albumin and extrahepatic metastasis. These findings show that patients with unresectable HCC who were administered TACE-JD survived significantly longer compared with those administered TACE or TACE-SOR.

Efficacy of transoral incisionless fundoplication (TIF) for the treatment of GERD: a systematic review with meta-analysis.

BACKGROUND: The efficacy of transoral incisionless fundoplication (TIF) performed with the EsophyX device (Redmond, Washington, USA) and its long-term outcomes in gastresophageal reflux disease (GERD) are debated. We, therefore, performed a systematic review with meta-analysis of studies evaluating the role of TIF in GERD. METHODS: A systematic search of EMBASE, SCOPUS, PubMed, and the Cochrane Library Central was performed. All original studies reporting outcomes in GERD patients who underwent TIF were identified. Only randomized controlled trials (RCTs) evaluating the efficacy of TIF, and prospective observational studies reporting outcomes after TIF were included. RESULTS: A total of 18 studies (963 patients) published between 2007 and 2015 were identified, including five RCTs and 13 prospective observational studies. The pooled relative risk of response rate to TIF versus PPIs/sham was 2.44 (95 % CI 1.25-4.79, p = 0.0009) in RCTs in the intention-to-treat analysis. The total number of refluxes was reduced after TIF compared with the PPIs/sham group. The esophageal acid exposure time and acid reflux episodes after TIF were not significantly improved. Proton-pump inhibitors (PPIs) usage increased with time and most of the patients resumed PPIs treatment at reduced dosage during the long-term follow-up. The total satisfaction rate after TIF was about 69.15 % in 6 months. The incidence of severe adverse events consisting of gastrointestinal perforation and bleeding was 2.4 %. CONCLUSIONS: TIF is an alternative intervention in controlling GERD-related symptoms with comparable short-term patient satisfaction. Long-term results showed decreased efficacy with time. Patients often resume PPIs at reduced doses in the near future.

Kinetic effects in the photomediated synthesis of silver nanodecahedra and nanoprisms: combined effect of wavelength and temperature.

Photomediated synthesis is a reliable, high yield method for the production of a variety of morphologies of silver nanoparticles. Here, we report synthesis of silver nanoprisms and nanodecahedra with tunable sizes via control of the reaction temperature and the irradiation wavelength. The results show that shorter excitation wavelengths and lower reaction temperatures result in high yields of nanodecahedra, while longer excitation wavelengths and higher reaction temperatures result in the formation of nanoprisms. The mechanism for the growth condition dependent evolution in the morphology of the silver particles is discussed as a kinetically controlled process. This is based on analysis of the reaction kinetics at various excitation wavelengths and temperatures. The energy barrier for the transformation from seeds to nanodecahedra is relatively high and requires a shorter wavelength. Thus longer wavelength illumination leads to the formation of nanoprisms. Thermodynamically stable five-fold twinning structures are shown to evolve from twin plane structures. The fast reaction rate at higher temperature favors the growth of nanoprisms by preferential Ag deposition on planar structures in a kinetics-controlled mode, while slower rates yield thermodynamically favored nanodecahedra.