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To investigate the efficacy and safety of dicycloplatin as chemotherapeutic regimen in transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).In this randomized, open-label, phase II trial, patients with unresectable HCC who were TACE treatment-naïve or experienced recurrence after surgical resection or ablation were enrolled at 7 centers in China from March 2019 to November 2019. Participants were randomly assigned (1:1:1) to receive TACE with chemotherapeutic regimen of dicycloplatin alone (group A1), dicycloplatin plus epirubicin (group A2), or epirubicin alone (group B). The primary endpoint was objective response rate (ORR). The secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and safety.The ORR at 6 months in group A1 (n = 22) was significantly better than that in group B (p = 0.093; 90% confidence interval [CI], 1.03-9.45). The DCR in group A1 was significantly higher than that in group B (p = 0.045; 90% CI, 1.29-12.88). There was no significant difference in DOR among the groups (p = 0.271). The median PFS were 6.00 and 3.05 months in groups A2 (n = 25) and B (n = 24), respectively (p = 0.061). Grade 3 or worse adverse events were similar among groups in the safety population (p = 0.173).TACE with dicycloplatin was comparably safe and well tolerable as epirubicin alone in patients with unresectable HCC. Compared with epirubicin alone, significant improvement in ORR and DCR when dicycloplatin was applied, as well as prolonged PFS when dicycloplatin plus epirubicin was applied, was generated.• To our knowledge, this is the first multicenter randomized trial to assess the efficacy and safety of TACE with dicycloplatin in patients with unresectable HCC. • This phase II trial showed that TACE with dicycloplatin alone or plus epirubicin was comparably safe and well tolerable as epirubicin alone. • Significant improvements in ORR, DCR when dicycloplatin was applied, and prolonged PFS when dicycloplatin plus epirubicin was applied were recorded compared with epirubicin alone.

Background The development of sensitive and specific MRI contrast agents for early diagnosis of hepatocellular carcinoma is highly demanded. Here, a peptide A54 (sequence: AGKGTPSLETTP) functionalized superparamagnetic iron oxide nanoparticles (SPIONs)-based magnetic nanostructured lipid carrier(A54-MNLC)as a hepatoma targeting negative magnetic resonance imaging (MRI) contrast agent was developed. Results Firstly, the A54 peptide functionalized PEGylated SA (A54-PEG-SA) was synthesized by the coupling reaction between A54 and NH2-PEG-SA. Then SPIONs-loaded MNLC(MNLC and A54-MNLC)were prepared by the solvent diffusion method. The A54-MNLC with a diameter of about 50 nm, and in vitro cell viability study revealed that the prepared A54-MNLC was cytocompatible in the given particles’ concentration ranges. The cellular uptake results indicated that A54-MNLC was able to be uptaken specifically by human hepatoma cell line (Bel-7402 cells) and also can be used as efficient probe for targeted MR imaging of cancer cells in vitro. The in vivo MR imaging experiments using an orthotopic implantation model further validated the hepatoma-targeting ability of A54-MNLC with a more remarkable MR imaging contrast effect compared to MNLC. Conclusions These results demonstrate that the A54-MNLC is a promising nanoplatform as a targeted MR imaging contrast agent for the diagnosis of hepatocellular carcinoma.

Background & Aims Placement of an irradiation stent has been demonstrated to offer longer patency and survival than an uncovered self-expandable metallic stent (SEMS) in patients with unresectable malignant biliary obstruction (MBO). We aim to further assess the efficacy of an irradiation stent compared to an uncovered SEMS in those patients. Methods We performed a randomized, open-label trial of participants with unresectable MBO at 20 centers in China. A total of 328 participants were allocated in parallel to the irradiation stent group (ISG) or the uncovered SEMS group (USG). Endpoints included stent patency (primary), technical success, relief of jaundice, overall survival, and complications. Results The first quartile stent patency time (when 25% of the patients experienced stent restenosis) was 212 days for the ISG and 104 days for the USG. Irradiation stents were significantly associated with a decrease in the rate of stent restenosis (9% vs. 15% at 90 days; 16% vs. 27% at 180 days; 21% vs. 33% at 360 days; p = 0.010). Patients in the ISG obtained longer survival time (median 202 days vs. 140 days; p = 0.020). No significant results were observed in technical success rate (93% vs. 95%; p = 0.499), relief of jaundice (85% vs. 80%; p = 0.308), and the incidence of grade 3 and 4 complications (8.5% vs. 7.9%; p = 0.841). Conclusions Insertion of irradiation stents instead of uncovered SEMS could improve patency and overall survival in patients with unresectable MBO. Lay summary For patients with unresectable malignant biliary obstruction (MBO), placement of a self-expandable metallic stent (SEMS) is a recommended palliative modality to relieve pruritus, cholangitis, pain, and jaundice. However, restenosis is a main pitfall after stent placement. Data from this first multicenter randomized controlled trial showed that insertion of an irradiation stent provided longer patency and better survival than a conventional metal stent. ClinicalTrials.gov ID: NCT02001779.

Background: The incidence of cryptococcal meningitis among immunocompetent patients increases, especially in China and imaging plays an important role. The current study was to find the correlation between magnetic resonance imaging (MRI) manifestation and clinical severity in nonhuman immunodeficiency virus patients with cryptococcal infection of central nervous system (CNS). Methods: A total of 65 patients with CNS cryptococcal infection from August 2014 to October 2016 were retrospectively included in this study. All the patients had MRI data and clinical data. The patients were divided into two groups according to whether the patients were confirmed with identifiable underlying disease. Comparison and correlation of MRI and clinical data in both groups were investigated using independent sample t-test, Chi-square test, Mann-Whitney test and Spearman rank correlation analysis. Results: In all 65 patients, 41 cases (41/65, 63.1%; Group 1) had normal immunity and 24 cases (24/65, 36.9%; Group 2) had at least one identifiable underlying disease. Fever, higher percentage of neutrophil (NEUT) in white blood cell (WBC), and increased cell number of cerebral spinal fluid (CSF) were much common in patients with underlying disease (Group 1 vs. Group 2: Fever: 21/41 vs. 21/24, χ2 = 8.715, P = 0.003; NEUT in WBC: 73.15% vs. 79.60%, Z = −2.370, P= 0.018; cell number of CSF: 19 vs. 200, Z = −4.298, P < 0.001; respectively). Compared to the patients with normal immunity, the lesions are more common in the basal ganglia among patients with identifiable underlying disease (Group 1 vs. Group 2: 20/41 vs. 20/24, χ2 = 7.636, P = 0.006). The number of the involved brain areas in patients with identifiable underlying disease were well correlated with the number of cells and pressure of CSF (r = −0.472, P = 0.031; r = 0.779, P = 0.039; respectively). Conclusions: With the increased number of the involved brain areas in patients with identifiable underlying disease, the body has lower immunity against the organism which might result in higher intracranial pressure and more severe clinical status. Key words: Central Nervous System; Clinical Status; Cryptococcal Meningitis; Immunity; Magnetic Resonance Imaging

Recent studies have shown that radiofrequency (RF) ablation therapy is a safe, feasible, and effective procedure for hepatic hemangiomas, even huge hepatic hemangiomas. RF ablation has the following advantages in the treatment of hepatic hemangiomas: minimal invasiveness, definite efficacy, high safety, fast recovery, relatively simple operation, and wide applicability. It is necessary to formulate a widely accepted consensus among the experts in China who have extensive expertise and experience in the treatment of hepatic hemangiomas using RF ablation, which is important to standardize the application of RF ablation for the management of hepatic hemangiomas, regarding the selection of patients with suitable indications to receive RF ablation treatment, the technical details of the techniques, therapeutic effect evaluations, management of complications, etc. A final consensus by a Chinese panel of experts who have the expertise of using RF ablation to treat hepatic hemangiomas was reached by means of literature review, comprehensive discussion, and draft approval.

Nowadays, there is a high demand for supersensitive contrast agents for the early diagnostics of hepatocarcinoma. It has been recognized that accurate imaging information is able to be achieved by constructing hepatic tumor specific targeting probes, though it still faces challenges. Here, a AGKGTPSLETTP peptide (A54)-functionalized superparamagnetic iron oxide (SPIO)-loaded nanostructured lipid carrier (A54-SNLC), which can be specifically uptaken by hepatoma carcinoma cell (Bel-7402) and exhibited ultralow imaging signal intensity with varied Fe concentration on T2-weighted imaging (T2WI), was first prepared as an effective gene carrier. Then, an endogenous ferritin reporter gene for magnetic resonance imaging (MRI) with tumor-specific promoter (AFP-promoter) was designed, which can also exhibit a decrease in signal intensity on T2WI. At last, using protamine as a cationic mediator, novel ternary nanoparticle of A54-SNLC/protamine/DNA (A54-SNPD) as an active dual-target T2-weighted MRI contrast agent for imaging hepatic tumor was achieved. Owing to the synergistic effect of A54-SNLC and AFP-promoted DNA targeting with Bel-7402 cells, T2 imaging intensity values of hepatic tumors were successfully decreased via the T2 contrast enhancement of ternary nanoparticles. It is emphasized that the novel A54-SNPD ternary nanoparticle as active dual-target T2-weighted MRI contrast agent were able to greatly increase the diagnostic sensitivity and specificity of hepatic cancer.

Colorectal cancer (CRC) is one of the most common malignancies, giving rise to serious financial burden globally. This study was designed to explore the potential mechanisms implicated with CRC and identify some key biomarkers. CRC-associated gene expression dataset (GSE32323) was downloaded from GEO database. The differentially expressed genes (DEGs) were selected out based on the GEO2R tool. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed to search the enriched pathways of these DEGs. Additionally, a protein-protein interaction (PPI) network was also constructed to visualize interactions between these DEGs. Quantitative Real-time PCR (qPCR) was further performed to valid the top5 up-regulated and top5 down-regulated genes in patients with CRC. Finally, the survival analysis of the top5 up-regulated and top5 down-regulated genes was conducted using GEPIA, aiming to clarify their potential effects on CRC. In this study, a total of 451 DEGs were captured (306 down-regulated genes and 145 up-regulated genes). Among these DEGs, the top5 up-regulated genes were DPEP1, KRT23, CLDN1, LGR5 and FOXQ1 while the top5 down-regulated genes were CLCA4, ZG16, SLC4A4, ADH1B and GCG. GO analysis revealed that these DEGs were mainly enriched in cell adhesion, cell proliferation, RNA polymerase II promoter and chemokine activity. KEGG analysis disclosed that the enriched pathway included mineral absorption, chemokine signaling pathway, transcriptional misregulation in cancer, pathways in cancer and PPAR signaling pathway. Survival analysis showed that the expression level of ZG16 may correlate with the prognosis of CRC patients. Furthermore, according to the connectivity degree of these DEGs, we selected out the top15 hub genes, namely MYC, CXCR1, TOP2A, CXCL12, SST, TIMP1, SPP1, PPBP, CDK1, THBS1, CXCL1, PYY, LPAR1, BMP2 and MMP3, which were expected to be promising therapeutic target in CRC. Collectively, our analysis unveiled potential biomarkers and candidate targets in CRC, which could be helpful to the diagnosis and treatment of CRC.

Background/Aims: Breast cancer (BC) starts as a local disease, but it can metastasize to the lymph nodes and distant organs. However, the metastatic process is still poorly understood. The mRNA microarray datasets GSE26910 and GSE33447 show that CXCL10 is up-regulated in BC, and the microRNA microarray dataset GSE38167 and a network meta-analysis of microRNA expression profile studies in human BC suggest that microRNA-34a (miR-34a) is down-regulated in BC. CXCL10 was predicted as a target of miR-34a by microRNA.org. In this study, we uncovered a CXCL10-independent mechanism by which miR-34a exerts its antimetastatic activity in BC. Methods: To investigate the clinical significance of miR-34a in BC, we collected cancer tissues and paracancerous tissues from 258 patients with BC. In addition, a series of inhibitors, mimics, and siRNAs was introduced into MCF-7 and T47D cells to validate the regulatory mechanisms by which miR-34a regulates CXCL10. Next, to better understand the pivotal role of TLR signaling pathway inhibition in MCF-7 and T47D cells, we blocked the TLR signaling pathway using OxPAPC, an antagonist of TLR signaling. Results: Among BC patients, miR-34a was down-regulated, CXCL10 was up-regulated, and the TLR signaling pathway was activated. Determination of luciferase activity revealed that CXCL10 was a target of miR-34a. Through gain- and loss-of-function studies, miR-34a was demonstrated to negatively regulate CXCL10; inhibit activation of the TLR signaling pathway; significantly suppress in vitro cell proliferation, migration, and invasion; and induce apoptosis. Conclusion: Our findings suggest that functional loss or suppression of the tumor suppressor CXCL10 due to induction of miR-34a leads to inhibition of the TLR signaling pathway during breast tumorigenesis, providing a novel target for the molecular treatment of breast malignancies.

To investigate the effectiveness of monoclonal antibody ((131)I-chTNT) and radiofrequency ablation (RFA) combination therapy in treating middle-advanced stage hepatocellular carcinoma (HCC). Thirty-four patients diagnosed with HCC patients, divided into two groups comprised of 22 and 12 cases were included in this retrospective study. The two groups received RFA with or without ((131)I-chTNT) therapy, respectively. The patients in these groups were followed up for a median of 31 and 35 months, respectively. Patient survival was evaluated using Kaplan-Meier method and safety profiles were determined by analyzing liver, thyroid, and bone marrow toxicities. This retrospective study showed that survival time of the patients who received combination therapy was significantly longer than that of the RFA group (P = 0.052). The median progress-free survival of patients in the two groups was 23 and 7 months, respectively, and the difference was significant (P = 0.04). Tumor recurred in 3.5-8.7 months in four of the combination group patients, among which three had newly developed lesions. The red blood cells and platelets counts were not altered on day 7 and 1 month of the treatment, however, number of white blood cells was significantly increased on day 7 which was reversed back to the normal range in 2 weeks. The ALT and AST were also not significantly altered on day 7 and 1 month of therapy. In middle-advanced stage HCC patients, the combination of (131)I-chTNT and RFA therapy was found to be significantly more effective than the RFA treatment alone as assessed in short-term follow-up. However, the dose we used was insufficient to completely block the local recurrence of the lesions with a diameter of 5 cm or larger.

MicroRNA (miRNA or miR) has been shown to play an important role in the initiation and development in many different cancers. Here, we demonstrated down-regulated expression of miR-27a-3p in hepatocellular carcinoma (HCC) tissues in comparison with that in adjacent normal liver tissues based on the TCGA database. Cells viability and apoptosis was measured by CCK-8 and flow cytometry assay. Cell invasion and migration was measured by Transwell and wound healing assay. The effect of miR-27a-3p on DUSP16 expression was evaluated by luciferase assays, and western blot assay. miR-27a-3p up-regulation by transfection with miR-27a-3p mimics attenuated SMMC-7721 and HepG2 cell viability, invasion as well as migration, obviously. Moreover, we found that dual specificity phosphatase 16 (DUSP16), also known as mitogen-activated protein kinase phosphatase 7 (MKP-7), is a target of miR-27a-3p. DUSP16 expression was obvious decrease by miR-27a-3p at both transcriptional and protein levels in both SMMC-7721 and HepG2 cells. DUSP16 expression in tissues of HCC was up-regulated in comparison with that in tissues of adjacent liver based on the TCGA database. Overexpression of DUSP16 significantly reversed the cell changes in viability, invasion and migration which resulted from miR-27a-3p up-regulation in SMMC-7721 and HepG2 cells. Our findings contribute to current understanding of the functions of miR-27a-3p and suggest a mechanism by which miR-27a-3p plays an anti-tumor role in the development of HCC by targeting DUSP16.

Xiao-Ming Wu,1 Jun-Feng Wang,1 Jian-Song Ji,2 Ming-Gao Chen,1 Jian-Gang Song1 1Department of Radiology, Jinhua People’s Hospital, Jinhua, 2Department of Radiology, Lishui Municipal Center Hospital, Lishui, People’s RepublicofChina Abstract: Although the efficacy of transcatheter arterial chemoembolization (TACE) has been recommended as first-line therapy for nonsurgical patients with hepatocellular carcinoma (HCC), it is difficult to accurately predict the efficacy of TACE. Therefore, this study evaluated the efficacy of TACE for HCC using magnetic resonance (MR) diffusion-weighted imaging (DWI). A total of 84 HCC patients who received initial TACE were selected and assigned to the stable group (n=39) and the progressive group (n=45). Before TACE treatment, a contrast-enhanced MR scan and DWI (b=300, 600, and 800 s/mm2) were performed on all patients. The modified response evaluation criteria in solid tumors were used for evaluation of tumor response. Receiver operating characteristic curve was employed to predict the value of apparent diffusion coefficient (ADC) for TACE efficacy. The ADC values of HCC patients in the progressive group were higher than those in the stable group at different b-values (b=300, 600, and 800 s/mm2) before TACE treatment. The area under the curve of ADC values with b-values of 300, 600, and 800 s/mm2 were 0.693, 0.724, and 0.746; the threshold values were 1.94×10-3 mm2/s, 1.28×10-3 mm2/s, and 1.20×10-3 mm2/s; the sensitivity values were 55.6%, 77.8%, and 73.3%; and the specificity values were 82.1%, 61.5%, and 71.8%, respectively. Our findings indicate that the ADC values of MR-DWI may accurately predict the efficacy of TACE in the treatment of HCC patients. Keywords: magnetic resonance imaging, diffusion-weighted imaging, hepatocellular carcinoma, transcatheter arterial chemoembolization, apparent diffusion coefficient

Summary Background The combination of stent insertion and single high-dose brachytherapy is a feasible and safe palliative treatment regimen in patients with unresectable oesophageal cancer. We aimed to further assess the efficacy of this treatment strategy compared to a conventional covered stent in patients with dysphagia caused by unresectable oesophageal cancer. Methods In this multicentre, single-blind, randomised, phase 3 trial, we enrolled patients with unresectable oesophageal cancer from 16 hospitals in China. We included adult patients (aged ≥20 years) with progressive dysphagia, unresectable tumours due to extensive lesions, metastases, or poor medical condition, and with clear consciousness, cooperation, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0–3. Eligible patients were randomly assigned (in 1:1 ratio, no stratification) to receive either a stent loaded with 125 iodine radioactive seeds (irradiation group) or a conventional oesophageal stent (control group). The primary endpoint was overall survival. Survival analyses were done in a modified intention-to-treat group. This study is registered with ClinicalTrials.gov, number NCT01054274. Findings Between Nov 1, 2009, and Oct 31, 2012, 160 patients were randomly assigned to receive treatment with either an irradiation stent (n=80) or a conventional stent (n=80). During a median follow-up of 138 days (IQR 72–207), 148 stents (73 in the irradiation group and 75 in the control group) were successfully placed into the diseased oesophagus in 148 participants. Median overall survival was 177 days (95% CI 153–201) in the irradiation group versus 147 days (124–170) in the control group (p=0·0046). Major complications and side-effects of the treatment were severe chest pain (17 [23%] of 73 patients in the irradiation group vs 15 [20%] of 75 patents in the control group), fistula formation (six [8%] vs five [7%]), aspiration pneumonia (11 [15%] vs 14 [19%]), haemorrhage (five [7%] vs five [7%]), and recurrent dysphagia (21 [28%] vs 20 [27%]). Interpretation In patients with unresectable oesophageal cancer, the insertion of an oesophageal stent loaded with 125 iodine seeds prolonged survival when compared with the insertion of a conventional covered self-expandable metallic stent. Funding National High-tech Research Foundation of China, National Basic Research Program of China, Jiangsu Provincial Special Program of Medical Science, National Scientific and Technical Achievement Translation Foundation, and National Natural Science Foundation of China.

This study evaluated if iodine-125 brachytherapy prophylaxis after radiofrequency ablation (RFA) prolongs time to recurrence (TTR) and overall survival (OS) of patients in high risk of locoregional hepatocellular carcinoma (HCC) recurrence. 116 patients with total tumor necrosis after RFA were divided into iodine-125 brachytherapy prophylaxis treatment group and control group. The primary endpoint was TTR, and secondary endpoints were OS and treatment-related adverse events. There were no significant differences among the baseline characteristics of two subgroups patients. The mean iodine-125 particles were 29.8 (26.59 ± 12.51 mCi) per patient. The mean follow-up was 25 months, and mean TTR of treatment and control groups were 21.7 and 15.9 months (P = 0.733); mean OS of two subgroups were 41.7 and 40.9 months (P = 0.316). There were no significant differences of 1-, 2-, 3-, 4-and 5-years TTR and OS and patients’ immunity pre- and 1 month post-treatment. Extrahepatic metastasis was found to have a statistically significant influence on TTR, and AFP, extrahepatic metastasis were found to have a statistically significant influence on OS by multivariate analysis. There was no major complications and procedure related death. Iodine-125 brachytherapy prophylaxis after RFA can’t improve TTR and OS of HCC patients who were in high risk of locoregional tumor recurrence.

Hepatocellular carcinoma (HCC) is a common malignant tumour, especially in Asia. Its prognosis is poor, and there are limited methods for predicting patient survival. This study was carried out to analyse the prognostic value of tumour-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in HCC patients. TILs were analysed in 57 randomly selected HCC patients. The prognostic effects of groups with high and low numbers were evaluated by the Kaplan-Meier and Cox model analyses. Although higher densities of CD3+, CD4+, and CD8+ cytotoxic lymphocytes (CTLs) as well as CD56+ NK cells and CD68+ macrophages were observed in peritumoural tissue, increased numbers of forkhead/winged helix transcription factor P3+ (FOXP3+) Tregs were found in intratumoural tissue. Additionally, regarding ICOS+ FOXP3+ Tregs, an increased prevalence in carcinoma was not only associated with the absolute number but also with the percentage of FOXP3+ cells. Higher Treg levels in tumour tissues indicated a worse prognosis, and the FOXP3+ Tregs/CD4+ T cells ratio was an independent prognostic factor for OS. Therefore, FOXP3+ Tregs, especially ICOS+ FOXP3+ Tregs, contribute to the immunosuppressive HCC microenvironment. High tumour-infiltrating Tregs are thought to be an unfavourable prognostic indicator of HCC.

Jian-Song Ji,1,2,* Min Xu,1,* Jing-Jing Song,1,* Zhong-Wei Zhao,1,* Min-Jiang Chen,1 Wei-Qian Chen,1 Jian-Fei Tu,1 Xiao-Ming Yang2 1Department of Radiology, Affiliated Lishui Hospital of Zhejiang University, Fifth Affiliated Hospital of Wenzhou Medical University, Central Hospital of Zhejiang Lishui, Lishui, People’s Republic of China; 2Department of Radiology, Lab-Yang, University of Washington, Seattle, WA, USA *These authors contributed equally tothis work Abstract: MicroRNA-126 (miR-126) has been found to promote angiogenesis, but the underlying mechanisms are still unclear. So, we conducted this study to explore the effect of miR-126 expression on angiogenesis in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). The expression levels of miR-126 and sprouty-related, EVH1 domain containing protein (Spred)1 in surgically resected HCC tissue, HCC tissue with TACE+ operation, and tumor-adjacent tissues were determined by quantitative real-time polymerase chain reaction. The expression levels of miR-126, Spred1, and vascular endothelial growth factor were found by quantitative real-time polymerase chain reaction and Western blot. The microvessel density (MVD) of tumor tissues was determined by immunohistochemical staining. The miR-126 and Spred1 expressions in HCC tissue with TACE + operation were elevated and decreased, respectively, as compared to those in surgically resected HCC tissues and tumor-adjacent tissues (all P

IL-17 and IL-17-producing cells have been found in many types of human cancers and murine models. However, the source of tumor-infiltrating IL-17 and IL-17-producing cells in HCC and the prognostic values remain poorly understood. A total of 57 HCC patients were enrolled in this study, and immunofluorescence double stain was used to evaluate the colocalization of CD3+ T cells, CD4+ T cells, CD56+ NK cells, CD20+ B cells, CD68+ Macrophages, and MCT+ mast cells with IL-17. The prognostic value of IL-17-producing cells was evaluated by Kaplan–Meier analysis and Cox regression model. MCT+ mast cells, but not other cells, were the predominant IL-17-producing cell type. Overall survival analysis revealed that the increasing intratumoral-infiltrated MCT+ mast cells were significantly associated with poor prognosis. Immunofluorescence double stain showed a positive correlation between the number of MCT+ mast cells and MCVs. These findings indicated the major IL-17-producing cells in HCC were MCT+ mast cells and these cells infiltration may promote tumor progression by angiogenesis. Increased MCT+ mast cells was associated with a poor prognosis, indicating therapy targeting MCT+ mast cells might be an effective strategy in controlling intratumor IL-17 infiltration and MCVs.

Objectives The aim of this study was to evaluate the technical and clinical outcomes of using laparoscopic radiofrequency (RF) ablation for treating large subcapsular hepatic hemangiomas. Methods We retrospectively reviewed our sequential experience of treating 124 large subcapsular hepatic hemangiomas in 121 patients with laparoscopic RF ablation. Results The mean diameter of the 124 hemangiomas was 9.1 ± 3.2 cm (5.0–16.0 cm). RF ablation was performed successfully in all patients. There were 55 complications related to the ablation in 26 patients, including 5 of 69 (7.3%) patients with hemangioma

The purpose of our study was to retrospectively evaluate the computed tomography (CT)/magnetic resonance imaging features of epithelioid angiomyolipoma of the liver (Epi-HAML), with pathology as a reference. We reviewed the CT/MRI findings of six lesions of Epi-HAML and found absence of adipose tissue in the lesions. In addition, recognizing the imaging features of no capsule, and hypervasularity with central punctiform or filiform vessels as a characteristic enhancement may distinguish Epi-HAML from other hepatic tumors.

Background It has been found that microRNA-423-5p (miR423-5p) is an oncogenic factor and frequently upregulated in gastric carcinoma. However, the involvement of miR423-5p in hepatocellular carcinoma (HCC) has been rarely reported. The aim of this study was to assess whether miR423-5p is aberrantly expressed in HCC tissues, and to characterize its roles in the cancerous biology of HCC. Methods HCC and corresponding nonmalignant tissues were obtained from 115 patients during liver transplantation to detect the expression level of miR423-5p. The miR423-5p mimic and inhibitor were transfected into LM3 cell line. Cell viability assay, cell cycle analysis, transwell invasion and migration experiments were used to evaluate the oncogenic role of miR423-5p. Results miR423-5p was significantly upregulated in HCC compared with nonmalignant tissues, and this upregulation was negatively associated with recurrence-free survival. For patients beyond the Milan criteria, low expression of miR423-5p was correlated with better prognosis. Functional analysis showed that miR423-5p enhanced the proliferative, invasive and migratory capacity of HCC cells. Conclusions miR423-5p contributed to the tumorigenesis and progression of HCC. It could be a new predictor in HCC patients beyond the Milan criteria and would help to improve patient outcomes and enlarge recipient pools of liver transplantation.

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease of unknown etiology defined by the combination of tubulointerstitial nephritis, uveitis, and biochemical abnormalities. It has been reported that TINU mainly affects adolescents and young women. Here we reported a special case regarding a 60-year-old man with acute renal failure due to TINU syndrome documented by renal biopsy. We present a rare case of an elderly patient, who had been suffering from a fever for 2 weeks, characterized by sudden onset and resolving spontaneously, and accompanied by extreme fatigue, loss of appetite, and shivering. Renal biopsy showed a tubulointerstitial nephritis, with polymorphonuclear infiltration and acute tubulitis. In the outpatient clinic, he was diagnosed with idiopathic bilateral anterior uveitis 1 month ago. Ophthalmological examination revealed anterior asymptomatic bilateral uveitis. Human leukocyte antigen (HLA) typing (HLA-DQA1∗0101/0201 and HLA-DQB1∗0303/0503) was found which supported the suspect of TINU syndrome. The patient was treated with oral prednisone (1 mg/kg) and continued for 8 weeks on tapering doses. Serum creatinine normalized within 3 and 6 months later renal function also recovered completely. This case highlights that TINU syndrome is probably an underdiagnosed disease responsible for some cases of idiopathic anterior uveitis in elderly male patients. It is of critical importance to be aware of this syndrome by nephrologist and ophthalmologists in this special population. Further studies are needed to elucidate clinical characteristic and pathogenesis of TINU syndrome in elderly population.

In the present study, we performed an arterioarterial prosthetic loop (AAPL) between the femoral artery and deep femoral artery as a new access in patients who did not have adequate vascular conditions for creating an arteriovenous fistula or graft. Between April 2005 and June 2014, 18 patients received AAPL as a vascular access. During the procedure, a polytetrafluoroethylene graft was anastomosed to the femoral artery and deep femoral artery and looped on the thigh. We assessed the reliability and safety of AAPLs by analyzing complication, primary and secondary patency rates, and postoperative blood flow. Eighteen patients (median age, 66 years; range, 43–96 years) underwent AAPL access placement under the general or local anesthesia. All patients were followed up for 3 to 38 months (mean, 24 months). Primary and secondary patency rates at 6 months were 94.5% and 88.8%, respectively, and at 3 years were 61% and 72%, respectively. After operation, one patient had infection, and another one had fat necrosis at the surgical incision site. To maintain the AAPL function, 5 surgical procedures in 4 grafts, including revision, thrombectomy, excision, and repair for bleeding were performed. More than 5000 hemodialyses were performed efficiently in our center. Our study shows that AAPL loop is an unusual but effective and safe procedure that may be a good alternative for the patients who do not allow the conventional hemodialysis access.

KRAS mutation in colorectal cancer (CRC) activates transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) to promote tumor progression. In the current study, we explored the potential effect of LYTAK1, a novel TAK1 inhibitor, against KRAS mutant CRC cells in vitro and in vivo. We found that LYTAK1 dose-dependently inhibited KRAS mutant CRC cell (HT-29 and SW-620 lines) growth, and induced cell cycle G1-S arrest. Further, LYTAK1 activated apoptosis in HT-29 cells and SW-620 cells, and apoptosis inhibitors almost reversed LYTAK1-mediated growth inhibition. While in KRAS wild-type (WT) CRC cell lines (DLD-1 and HCT-116), LYTAK1 had almost no effect on cell growth, cell cycle progression, or cell apoptosis. In KRAS mutant HT-29 cells and SW-260 cells, LYTAK1 blocked TAK1 activation or phosphorylation at Thr-184/187. Activation of nuclear factor κB (NF-κB) in these cells, detected by phosphorylations of p65 and IκB kinase α (IKKα) as well as expression of NF-κB-regulated gene cyclin D1, was significantly inhibited by LYTAK1. Further, LYTAK1 treatment resulted in downregulation of β-catenin and Wnt response gene Axin 2, indicating Wnt inactivation. In vivo, oral LYTAK1 significantly inhibited HT-29 xenograft growth in nude mice. Together, these results show that LYTAK1 inhibits KRAS mutant CRC cell growth both in vitro and in vivo. LYTAK1 might be investigated as a novel agent against CRC with KRAS mutation.

To explore the efficacy and safety of remifentanyl and propofol injection in total intravenous anesthesia for percutaneous radiofrequency ablation.60 patients scheduled for PRFA were divided randomly into two groups:group A and group B. Each group contained 30 patients. Those in group A received remifentanyl and propofol injection, and the patients in group B were given oxycodone hydrochloride. The mean arterial pressure (MAP), heart rate (HR) and pulse oxygen saturation (SPO2) were measured and recorded by monitor during the operation. The chest muscle rigidity, respiratory depression, nausea and vomitting, hypotensio and VAS were also recorded.Compared with the preoperative,MAP, HR in group A decreased significantly during the operation, increased in group B (P0.05). VAS was significantly lower in group A than that in group B (P0.05). 2 patients had respiratory depression, 1 patient had nausea and vomiting reaction in group A.2 patients had vagus reflex, 3 patient had nausea and vomitting reaction in group B.Total intravenous anesthesia with remifentanyl and propofol for PRFA is safe and reliable. Respiratory and circulation should be monitored instantly and strictly.

To explore the diagnostic value of T2-weighted gradient-echo magnetic resonance imaging (MRI) in cerebral microbleeds (CMBs) and its clinical significance.The distribution of CMBs and follow-up observations were performed by routine T1WI, T2WI and T2-weighted gradient echo sequence in 634 patients clinically suspected for stroke.In 149 patients, a total of 1140 CMBs occurred predominantly in cortex-subcortical area (n = 471, 41.31%), basal ganglia (n = 289, 25.35%), thalamus (n = 199, 17.45%), brain stem (n = 90, 7.89%) and cerebellum (n = 91, 7.98%). Among them, 137 patients had various degrees of ischemic brain changes, displayed iso-intensity or hypo-intensity on T1WI, hyper-intensity on T2WI and FLAIR in basal ganglia, white matter around sided ventricle and brain stem. There were 23 patients with cerebral infarction and 5 with CMBs after hemorrhagic brain stroke. And 12 of them had new hemorrhagic stroke in 2-6 months.T2-weighted gradient echo MRI has obvious advantages in the detection of CMBs. The presence of CMBs suggests a risk of cerebral hemorrhage.

ileus caused by gallstone has become more and more common recently due to popular usage of computed tomography (CT) and magnetic resonance imaging (MRI). In the past, imaging diagnosis relied primarily on conventional radiography and contrast-enhanced fluoroscopy. 1 CT has subsequently been shown to be quite useful for this diagnosis. 2,3 Recently, MR cholangiopancreatography (MRCP) has emerged as a valuable noninvasive technique for evaluation of biliary disease. Here we described the CT, MRCP and gastroenterography findings in two patients with unusual form of gallstone ileus (GI), one is Bouveret's syndrome and the other is negative gallstone-induced ileus. Few reports about GI with angiografin and MRCP findings of Bouveret's syndrome has been published. 3-8

The function of FAM9C encoding a testis-exclusively expressed and nuclear-localized protein remains unknown. In the present study, we evaluated the role of FAM9C in human hepatocellular carcinoma. We found that among three FAM9 family members, only FAM9C was frequently upregulated in HCC specimens compared with that in corresponding adjacent non-cancer liver tissues. FAM9C was located in the nucleus of HCC cells, as shown by both western blotting and immumofluorescence assays. Significantly, FAM9C overexpression promoted proliferation, clonogenicity in an anchorage-dependent manner, in vivo tumorigenicity of YY-8103, and Huh-7 cells. In contrast, FAM9C knockdown suppressed proliferation, anchorage-dependent colony formation and in vivo tumorigenicity of QGY-7703, and BEL-7404 cells. However, FAM9C had no significant effects on cell cycle progression when FAM9C was stably overexpressed in Huh-7 cells or knocked down in BEL-7404 cells. Most importantly, FAM9C regulated activation of Akt and UV-induced apoptosis in HCC cells. FAM9C overexpression increased the phosphorylation levels of Akt and anti-apoptotic ability of Huh-7 cells, whereas endogenous FAM9C knockdown reduced the phosphorylated levels of Akt and anti-apoptotic ability of BEL-7404 cells. Furthermore, the anti-apoptotic function of FAM9C could be prevented when the PI3K-Akt pathway was in a loss-of-function caused by RNA interference against Akt or PI3K inhibitor LY294002 in HCC cells. Taken together, our data demonstrate that FAM9C as a novel cancer testis gene plays an anti-apoptotic role in human hepatocellular carcinoma through activating the PI3K/Akt signaling pathway, and serves as a promising target for HCC therapy.

To prepare and characterize the compound Epirubicin hydrochloride and Gadopentetate meglumine (Gd-DTPA) nanoparticles, and evaluate its properties from rabbits in vivo and in vitro.The compound Epirubicin hydrochloride and Gd-DTPA nanoparticles were prepared by double emulsion-solvent evaporation method. The main effective factors were orthogonal designed. The characteristics such as drug entrapment efficiency, drug loading, and drug utilization were assayed in vitro. MR imaging effect of the VX2 rabbit hepatoma model were observed after injecting the drug-loaded nanoparticles through the hepatic artery intubation in vivo.The drug encapsulation efficiency of the nanoparticles, drug loading and drug utilization were 33.8% ± 3.4%, 0.225% ± 0.052%, and 69.6% ± 4.3% under the optimized prescription, respectively. The mean size of the nanoparticles was 180.6 nm, the drug release continued in 48 h with good MR imaging effect.Compound Epirubicin hydrochloride and Gd-DTPA Nanoparticles were in simply preparation and showed sustained drug release properties. These novel nanoparticles with detecting function could develop of epirubicin hydrochloride targeted therapy of liver cancer.

To prepare compound epirubicin hydrochloride-loaded polymeric nanoparticles of L-lactic-co-glycolic acid and establish their quality control.The emulsion-solvent evaporation method was employed to prepare and freeze-dry the compound epirubicin hydrochloride-loaded polymeric nanoparticles of L-lactic-co-glycolic acid after the addition of lactose. The contents and cumulative release of epirubicin hydrochloride and dimeglumine gadopentetate were detected simultaneously by RP-HPLC (reverse phase-high performance liquid chromatography).The above nanoparticles were prepared and the quality standards for simultaneously determining the contents of epirubicin hydrochloride and dimeglumine gadopentetate established primarily. The contents of epirubicin hydrochloride and dimeglumine gadopentetate in compound preparation were 100.6% ± 1.6% and 99.1% ± 1.9% respectively. And two compositions could be completely released within 9 days.The preparation method of nanoparticles is simple and their quality control feasible.

To discuss the computerized tomography (CT) finding of early postoperative inflammatory small bowel obstruction (EPISBO) so as to enhance its diagnostic level.The CT findings of 35 EPISBO cases proved by surgery were retrospectively analyzed from August 2003 to October 2008.The main CT findings were as follows: (1) Incomplete small bowel obstruction; (2) Thickening and edema of focal or global bowel wall; (3) Local or diffuse effusion mainly around operative incision; (4) Without definite obstruction point or bent adhesive point; (5) Locally ring-shaped or delayed enhancement during an enhancement scan.Spiral CT has an important value in the diagnosis of EPISBO.

To discuss the value of spiral CT in diagnosing infantile intestinal malrotation.The spiral CT findings and clinical data of 23 cases of operatively-confirmed infantile intestinal malrotation were retrospectively analyzed.Twenty-three cases of infantile intestinal malrotation were all diagnosed by SCT and confirmed by surgery. The main findings were as follows: whirlpool or concentric circle sign in mesenteric root with midgut volvulus (n = 16); duodenum assumed as "Z" or olecranon spur sign (n = 18); inverted transposition or vertical arrangement of superior mesenteric artery and vein (n = 13); abnormal sign of ileocecal junction and colon in right lower quadrant (n = 23).Spiral CT scanning has an important value in the early diagnosis of infantile intestinal malrotation.

To investigate the role of various multiple slice computed tomography (MSCT) and its reconstruction techniques in diagnosing intestinal obstruction (IO).419 cases diagnosed as IO by MSCT and proved by operations or follow up were analysed, retrospectively.As to the presence diagnosis of IO, in all the patients, CT diagnosis was consistent with the final results, while X-ray plain film had an accuracy of only 60.5% (237/392). The causes of IO included adhesion 88.6% (117/132), neoplasm 98.2% (112/114), external or internal hernia 93.5% (43/46), intussusception 97.4% (37/38), inflammatory disease (including 7 cases paralytic ileus, 83.3%, 30/36), enterolith 88.5% (23/26), bowel torsion 90.9% (10/11), trauma 62.5% (5/8), ischemia 100% (6/6), congenital lesion (100%, 2/2). Total sensitivity of etiology diagnosis with CT was 92.8% (384/419), with accuracy, false positive and false negative to be 91.9% (385/419), 1.0% (4/419) and 7.2% (31/419), respectively.MSCT can correctly diagnose the presence of the ileus, as well as can obviously enhance the accurate rate of diagnosis of its causes and characteristics, position, existence of close-loop and strangulation.

Poland's syndrome is a rare congenital anomaly characterized by unilateral chest wall hypoplasia and ipsilateral hand abnormalities. It has been reported in association with various malignancies and other developmental defects. We report here the case of a 58-year-old woman with Poland's syndrome who developed breast cancer in the ipsilateral normal breast. A review of the literature reveals that two studies of breast carcinoma associated with Poland's syndrome have been reported, but this paper is the first example of a carcinoma occurring in an otherwise normal breast associated with Poland's syndrome.

To evaluate the spiral CT and its reconstruction techniques in diagnosis and localization of gastrointestinal stromal tumor originated in the small intestine.The data of spiral CT scan and MPR, STS-MIP of 24 patients with gastrointestinal stromal tumor in the small intestine confirmed pathologically were analyzed retrospectrvely.Of 24 cases, 1 had multiple tumor, while the other 23 had single one. Seventeen of these tumors were benign and 7 malignant, with 2 in the duodenum, 12 in the jejunum and 10 in the ileum. The range of tumor diameters was from 2.5 to 12 cm. The main clinical characters of the tumors on the CT image: (1) The tumor of 15 cases located outside of the enteric cavity, 7 inside of the enteric cavity or presented as thicken bowel wall and 2 showed as niche sign. (2) The tumor shape of 19 cases were round-like, and 5 lobulated or irregular. (3) The tumor density of 12 cases was homegeneous, 7 heterogeneous and 5 map-like in the center. (4) The tumor enhancement style in 19 cases were homegeneous in dynamic enhanced scan, and 16 were slightly or mildly heterogeneous in the artery phase but apparently enhanced in the venous and equilibrium phase, with 5 showed as fast-in fast-out enhanced mode. Of those, one showed obvious enhancement in artery phase, while 2 did not. (5) The tumor of 2 cases had no clear margin and had invaded the surrounding tissue. (6) The arteries supplying tumors in 20 cases were demonstrated by multiple planar reconstruction (MPR), sliding thin slab-maximum intensity projection (STS-MIP). The accuracy of diagnosis and localization of gastrointestinal stromal tumor in the small intestine by spiral CT scan combined with MPR, STS-MIP were 91.7% (22/24) and 95.8% (23/24), respectively.Spiral CT and its reconstruction techniques (MPR, STS-MIP) can play an important role in the differential diagnosis and localization of gastrointestinal stromal tumor originated in the small intestine.

To evaluate the value of spiral computed tomography (CT) in diagnosis of adult intussusception.Sixty-eight patients with adult intussusception, 42 males and 28 females, aged 52.5 (30-82), with the course of 3 days-13 months, underwent plain CT scanning and biphase CT enhanced scanning of the abdomen. Operation was performed later.Sixty-six of the 68 patients (97.1%) were diagnosed as with intussusception by spiral CT. Direct signs of intussusception were shown in 66 patients: concentric circle sign in 66 cases, vessel involvement in 61 cases, and fat sign in 58 cases. And main indirect signs were shown in 19 cases: ring sign in 19 cases, ileus sign in 24 cases, and ascitic fluid sign in 4 cases. Other signs included mesenteric infiltration in 4 cases and retroperitoneal lymphadenectasis in 8 cases. Operation performed later showed an accurate rate of etiological diagnosis of intussusception by CT of 72.1%.Spiral CT has important value in diagnosis of adult intussusception and its etiology. The specific signs to diagnose adult intussusception are concentric circle sign, vessel involvement and fat sign.

To evaluate the diagnostic value of spiral CT and its reconstruction techniques in the diagnosis of extraluminal type gastric stromal tumors.The data of spiral CT performed 1 week before operation of 17 extraluminal type cases, 11 males and 6 females, aged 35.5 (13-67), from 33 patients of gastric stromal tumors proved by pathology and immunohistochemistry, were analyzed retrospectively.The accuracy rates of level diagnosis and qualitative diagnosis of extraluminal type gastric stromal tumor by spiral CT were 88.2% and 82.4% respectively. The main CT manifestations included: (1) extraluminal mass connected with the gastric wall, with round or lobulated margin and characteristic horn-like appearance and direct invasion, more than 5.0 cm in diameter; (2) inhomogeneous density of mass, including mild to moderate uneven enhancement in artery phase and obvious enhancement in vein and delay phase in 15 cases, and obvious enhancement in artery phase and decrease of enhancement in portal vein phases in 2 cases. (3) Irregular niches and sinus in the margins of the intraluminal masses (n = 11) and unclear border of the masses and invasion into nearby structures (n = 9); (4) connection of the tumor and stomach wall by broad boundary or failure to distinguish the tumor and stomach wall; and (5) invasion to the surrounding tissues and organs as a sign of malignant tumors.Spiral CT and its reconstruction techniques have important value in level diagnosis and qualitative diagnosis of extraluminal type gastric stromal tumors.