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It has not been demonstrated that computational fluid dynamics (CFD) can be used to model central venous stenosis (CVS), nor that hemodynamic changes in CVS treated with stent placement can be anticipated. The purpose of this study was to demonstrate the hemodynamic performance of CVS patients treated with stent placement.Patient-specific geometric models were constructed using computed tomography images of veins from hemodialysis patients treated with stent placement. CFD simulation based on geometry was performed using ANSYS-15 to compare pressure quantitatively, wall shear stress (WSS), and flow velocity in the brachial vein before and after stent placement.Following a covered stent placement, the swelling of the left upper extremity was relieved. Prior to stent implantation, the maximum and mean brachial vein wall pressures were 465.2 Pa and 224.609 Pa, respectively. It was determined that the maximum WSS value was 8.449 Pa and that the mean WSS value was 0.743 Pa. The maximum and mean flow velocities were 1.16 and 0.173 m/s, respectively. After stent placement, the maximum wall pressure, maximum WSS, and maximum flow velocity dropped by 59.4%, 71.2%, and 57.8%, respectively. The mean wall pressure, mean WSS, and mean flow rate decreased by 43.5%, 52.7%, and 17.6%, respectively.Hemodynamics of CVS in hemodialysis patients exhibited turbulent, imbalances and disorders, which can be improved by stent placement.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide. Emerging evidence has revealed the vital functions of microRNAs (miRNAs) in cancer malignant progressions. miR-375 has been verified to serve as an antioncogene in tumorigenesis and a potential therapeutic target in various types of cancer. In this study, we aimed to determine the role of miR-375 in the regulation of chemoresistance and metastasis of HCC. Differentially expressed miR-375 and NCAPG2 were externally validated using expression data from The Cancer Genome Atlas (TCGA) database. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression levels of miR-375 in HCC tissues and cell lines. miR-375 mimics and NCAPG2-overexpression were transfected into HepG2 and Huh7 cells to establish miR-375 overexpression models. Cell Counting Kit-8, Transwell, and flow cytometry experiments were conducted to monitor cell proliferation, migration, and apoptosis. The targeting relationship between miR-375 and non-SMC condensin II complex subunit G 2 (NCAPG2) was determined by qRT-PCR, western blot, and luciferase reporter gene assay. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted using Gene Set Enrichment Analysis (GSEA). The pathway enrichment analysis was used to predict the potential pathways for further study. miR-375 was significantly downregulated in HCC tissues and cells compared to adjacent tissue and normal hepatocyte cell line respectively while NCAPG2 was upregulated. The targeting relationship was verified by luciferase reporting assay, and miR-375 could target the 3'UTR of NCAPG2 mRNA and effectively suppress NCAPG2 protein expression. Replenishing of miR-375 significantly repressed HCC cell proliferation and migration, and induced cell apoptosis. Overexpression of NCAPG2 recovered those biological abilities in miR-375 overexpressed cells. Collective data suggested that miR-375 served as a tumor suppressor via regulating NCAPG2. Replenishing of miR-375 or knockout of NCAPG2 could be therapeutically exploited for HCC.

Background To explore the effect of the optimal time interval from preoperative transarterial embolization to surgery of carotid body tumors by analyzing surgery-related indicators. Methods This single-center retrospective review included 103 patients and 108 carotid body tumor resections performed between June 2010 and June 2020. All carotid body tumors were divided into three groups based on interval time between transarterial embolization and surgery: 1-day group (G1), 2-day group (G2), and 3-day group (G3). Demographics, inflammatory biomarkers, periprocedural details, and postoperative outcomes were analyzed. Results Among 103 patients, 48.54% were women, and the mean age was 37.07 years. The tumor sizes were 43.83, 44.31, and 42.84 mm in G1, G2, and G3, respectively, and the blood loss and operative time were 163.68, 331.54, and 683.68 mL, and 182.32, 216.31, and 280.79 mins with the prolonged time interval, respectively. Compared with pretransarterial embolization, the expression of white blood cells (109/L) and neutrophils (109/L) were obviously increased post-transarterial embolization in the three groups (G1: white blood cells 6.81 vs 9.32; neutrophils 0.54 vs 0.74, all P Conclusion The optimal time interval between preoperative transarterial embolization and surgical resection resulted as 1 day as patients in this group showed obvious lower blood loss and shorter duration of operation than patients in other groups. Both inflammation and recanalization provided support for these results at some extent.

Although immunotherapy of hepatocellular carcinoma using immune checkpoint inhibitors has achieved certain success, only a subset of patients benefits from this therapeutic strategy. The combination of immunostimulatory chemotherapeutics represents a promising strategy to enhance the effectiveness of immunotherapy. However, it is hampered by the poor delivery of conventional chemotherapeutics. Here, it is shown that H-ferritin nanocages loaded with doxorubicin (DOX@HFn) show potent chemo-immunotherapy in hepatocellular carcinoma tumor models. DOX@HFn is constructed with uniform size, high stability, favorable drug loading, and intracellular acidity-driven drug release. The receptor-mediated targeting of DOX@HFn to liver cancer cells promote cellular uptake and tumor penetration in vitro and in vivo. DOX@HFn triggers immunogenic cell death to tumor cells and promotes the subsequent activation and maturation of dendritic cells. In vivo studies in H22 subcutaneous hepatoma demonstrate that DOX@HFn significantly inhibits the tumor growth with30% tumors completely eliminated, while alleviating the systemic toxicity of free DOX. DOX@HFn also exhibits robust antitumor immune response and tumoricidal effect in a more aggressive Hepa1-6 orthotopic liver tumor model, which is confirmed by the in situ magnetic resonance imaging and transcriptome sequencing. This study provides a facile and robust strategy to improve therapeutic efficacy of liver cancer.

Objective: Our objective was to evaluate the feasibility of XperCT combined fluoroscopy to guide sharp recanalization for the treatment of chronic thoracic venous occlusive disease in hemodialysis patients. Methods: The records of hemodialysis patients with chronic thoracic venous occlusive disease who received endovascular sharp recanalization after conventional techniques failed were retrospectively reviewed. The sharp devices used for recanalization included the stiff end of a guidewire, Chiba biopsy needle, RUPS-100 set, and transseptal needle. The needle was advanced toward a target placed at the opposite end of the occlusion and was guided by fluoroscopy and/or XperCT. While the guidewire crossed the occlusion, endovascular procedures such as percutaneous angioplasty were performed for the treatment of the occlusion. Results: The analysis included 32 sharp thoracic vein recanalization procedures in 29 patients. Two attempts in one patient failed, and in one patient the first attempt failed but the second attempt was successful. In one patient, two separate successful procedures were performed, and the other 26 procedures in 26 patients were successful. The overall technical success rate of sharp recanalization was 90%. The mean number of puncture attempts in the combined group was less than that of the fluoroscopy-guided alone group (2 vs 5, p 0.05) was no different. There was no statistical difference in procedure-related complications between the groups. Conclusion: XperCT can facilitate sharp recanalization for the treatment of chronic thoracic venous occlusive disease in hemodialysis patients.

The development of novel chemoembolization agents to improve the treatment efficacy of transarterial chemoembolization (TACE) against liver cancer remains an urgent need in clinical practice. Herein, a versatile composite microsphere with upper critical solution temperature (UCST) properties was prepared to encapsulate polydopamine coated superparamagnetic iron oxide nanoparticles (SPION@PDA) and doxorubicin for simultaneous chemoembolization and photothermal therapy. The microspheres were spherical with an average diameter of 100-300 μm and exhibited favorable drug loading capability as well as strong photothermal effect. Strikingly, synergistic enhancement of photothermal therapy and chemotherapy against chemoresistant liver cancer cells was achieved. The in vivo therapeutic efficacy and safety evaluations were performed using rabbit VX2 liver tumor models. It was revealed that a single treatment of the combination of TACE and photothermal procedure resulted in 87.5% complete response and 12.5% partial response for the microsphere group, whereas all tumors in the control group progressed rapidly. Contrast-enhanced computed tomography (CT) evaluation indicated that the tumor diameter decreased by 91.5% after treatment, while that in the control group increased by 86.5%. The pathology-proven tumor necrotic rate was 87.2%, which significantly surpassed that of 65.2% in the control group. Furthermore, serum liver enzyme and biochemical studies indicated a temporary liver injury which can be fully recovered. Our findings demonstrated that this microsphere may be advantageous for enhancing therapeutic efficacy of TACE against liver cancer.

BACKGROUND: Liver function is a key determinant for the survival of hepatocellular carcinoma (HCC) patients receiving transarterial chemoembolization (TACE). However, establishing robust prognostic indicators for liver insufficiencies and patient survival remains an unmet demand. This retrospective study evaluated the prognostic value of splenic volume (SV) in HCC patients undergoing TACE. METHODS: A total of 67 HCC patients who underwent at least two consecutive TACE procedures were retrospectively included in this study. Comprehensive clinical information and follow-up data were collected, and the SV was measured based on dynamic contrast enhanced images. Risk factors of SV enlargement were assessed. The prognostic value of SV on survival was analyzed and compared with Child-Pugh (CP) classification and albumin-bilirubin (ALBI) grade. RESULTS: The baseline SV was 299.74±143.63 cm(3), and showed a moderate and statistically significant correlation with CP classification (R=0.31, P

Background The purpose of the present study was to evaluate the technical feasibility and safety of sharp recanalization for central venous occlusive disease (CVOD) in patients requiring hemodialysis. Methods Patients with CVOD requiring hemodialysis who had undergone endovascular recanalization using sharp devices, including the stiff end of a guidewire, Chiba needle, or RUS-100 to cross occluded segments after conventional techniques had failed were included. The needle was guided toward a target placed at the opposite end of the occlusion. Although the guidewire was passed though the occlusion, subsequent procedures such as percutaneous transluminal angioplasty could be performed. Results A total of 27 sharp recanalization procedures in 25 patients were performed. Two attempts failed, 1 patient had undergone two separate successful procedures, and 23 procedures in 23 patients were successful. The overall technique success was 92.6%. The stiff end of a guidewire was the first choice for all the procedures, and recanalization was achieved in 18 patients (66.7%). A Chiba biopsy needle was used in six procedures (22.2%), with 100% technical success. A RUPS-100 set was used in two procedures (7.4%), with one aborted because of concern for complications. The occlusion was subsequently crossed using a Chiba needle. Four minor adverse events (two of mediastinal hematoma and two of chest pain) had occurred, and two major adverse events (pericardial tamponade and acute pleural effusion in one patient [4%], treated with the guidewire stiff-end technique, who recovered after drainage) had occurred. Conclusions Sharp recanalization is safe and feasible with high technical success for CVOD in patients requiring hemodialysis who cannot be recanalized using conventional techniques.

Background: Up-regulated expression of copper chaperone for superoxide dismutase (CCS) is identified in a multitude of tumors and is closely related to more malignant tumoral biological behaviors. However, little is known about the role of CCS in hepatocellular carcinoma (HCC). This study aims to explore the expression pattern and the significance of CCS in human HCC.Methods Fresh samples of HCC with paired adjacent tissues, as well as the clinicopathological features and prognosis data were obtained from 32 patients who underwent hepatectomy from January 2018 to December 2018. The expression levels of CCS and a series of representative malignant biomarkers in HCC and adjacent tissues were investigated by western blotting and immunohistochemistry staining, respectively. The correlation between the expression status of CCS and the activities of selected malignant biomarkers and important drive genes of HCC oncogenesis, patient’s clinicopathological features and prognosis, were analyzed. Additional bioinformatics investigation of dataset retrieved from TCGA, the GEPIA, HPA, and Kaplan-Meier plotter (KM plotter) database were performed to further explore the role of CCS in human HCC and to validate the aforementioned findings. Results A unique express pattern was found that the majority of the HCC tumor (78.1%, 25/32) presented a lower expression of CCS as compared with that in adjacent tissues, whereas in the minority of the tumor (22.9%, 7/32) the expression of CCS was determined as higher. The distinctive CCS express status in HCC was further validated by the analysis of the data from TCGA and the GEPIA database. Furthermore, it was found that the expression level of CCS was significantly correlated with the those of the selected biomarkers including Ki67, vimentin, GPC3, and E-cadherin, which were also confirmed by the bioinformatic study. On the clinicopathological features, the expression of CCS was reversely correlated with ES grade and TNM stage to some extent, whereas there were no apparent correlations were proved with the remaining parameters included. Additional explorations revealed that there is a significant correlation between the CCS gene and a series of the driving/high-frequency mutation genes of various signal pathways in the development and progression of HCC. Despite statistic significant was not achieved, patients with higher CCS expression lever were prone to have a better prognosis. And a robust prognostic value of CCS was further proven in bioinformatic study. Conclusion HCC presented a unique lower expression pattern of CCS which reversely correlated with the more malignant tumoral features and poor prognosis as demonstrated by both experimental and bioinformatic studies. These findings improved our knowledge for understanding of the unique biological behavior of human HCC.

Nitric oxide (NO) plays a pivotal role in the cutaneous healing process and a topical supplement of NO is beneficial for wound repair. In this work, a novel polyethylenimine (PEI) based diazeniumdiolate nitric oxide donor was prepared. The obtained polymer (PEI-PO-NONOate) was characterized by Fourier transform infrared (FTIR) spectroscopy, UV-vis absorption spectra, and nuclear magnetic resonance (NMR). The PEI-PO-NONOate polymer was stable under anhydrous conditions at different temperatures. A total of 0.57 μmol gaseous NO was released from 1.0 mg of the PEI-PO-NONOate polymer in PBS of pH 7.4 and it presented a proton-driven release pattern. Furthermore, the PEI-PO-NONOate polymer exhibited a controlled release profile sustained for over 30 hours within the polyethylene glycol (PEG) mixture system. Cytotoxicity evaluation was performed on L929 cells. Full-thickness excisional cutaneous wound models of mice were prepared and the PEI-PO-NONOate polymer was applied to investigate its effects on wound healing. The results revealed that the PEI-PO-NONOates exhibited good biocompatibility. It was also found that the PEI-PO-NONOate polymer promoted cutaneous wound healing and closure with enhanced granulation tissue formation, collagen deposition, and angiogenesis, as compared to the control. In summary, a novel nitric oxide releasing polymer with high loading efficiency and a controlled release profile was developed which presented the potential for application in the acceleration of cutaneous wound healing.

Purpose To investigate the optimal starting time point of sorafenib therapy in suppressing the tumor-promoting effects of VEGF up-regulation, which is frequently found after local therapy in clinical practice. Methods VEGF was intravenously injected to imitate the evaluated expression after local tumor therapy, such as TACE. A total of 40 SD rats bearing hepatic tumors were randomly divided into four groups and sorafenib was administered at different timepoints: (A) control group: VEGF injection only; (B) initiating sorafenib 72 h prior to VEGF injection; (C) initiating sorafenib simultaneously with VEGF injection; (D) initiating sorafenib 72 h post-VEGF injection. The rate of tumor growth, median survival time, expression of VEGF, and microvessel density (MVD), as determined by immunohistochemical (IHC) examination, were compared. Results The results revealed that the tumor size and median survival time were significantly different between the three sorafenib groups compared to the control group (p