Small Oversized Stent Graft Is Associated With Increased Patency for the Treatment of Central Venous Disease in Hemodialysis Patients.

PURPOSE: The purpose of this study was to identify the independent predictors of higher patency rates and investigate the selection of specifications of stent graft in the treatment of central venous disease. MATERIALS AND METHODS: This retrospective study included 54 patients who underwent stent-grafts' placement for the treatment of central venous disease between March 2017 and September 2022 at a tertiary hospital. The demographic data for the patients and the clinical data of the treated lesions were collected and analyzed. The patency rates of the treated lesions with different oversizing range were calculated via the Kaplan-Meier and log-rank analyses. The multivariate Cox proportional hazard models were constructed to identify the independent predictor of the target site primary patency. RESULTS: The median follow-up period was 21.5 months. The primary patency rates of the target sites were 90.7%, 72.2%, and 55.1% at 6, 12, and 24 months, respectively. The assisted primary patency rates of the lesions were 96.3%, 92.5%, and 80.3% at 6, 12, and 24 months, respectively. The log-rank analysis showed that the stent-grafts' placement with small oversizing had significantly higher primary patency rates than those with large oversizing (p=0.022). The multivariate analysis revealed that concomitant stenosis and large oversizing stent graft were the independent predictors of target site primary patency. CONCLUSIONS: Stent grafts showed reasonable primary patency for the treatment of central venous disease in hemodialysis patients. A stent graft with small oversizing is associated with better target site primary patency rates than those with large oversizing. CLINICAL IMPACT: Stent grafts showed reasonable primary patency for the treatment of central venous disease in hemodialysis patients. Few studies, however, have explored the efficiency of stent grafts to treat CVD by considering different factors such as sizing considerations, the rate of oversizing percentage, etc. A stent graft with small oversizing is associated with better target site primary patency rates than those with large oversizing. Excessive oversizing should be avoided to prevent infolding or stent collapse.

Analysis of transjugular intrahepatic portosystemic shunt by hemodynamic simulation.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS), which artificially creates a portocaval shunt to reduce portal venous pressure, has gradually become the primary treatment for portal hypertension (PH). However, there is no prefect shunting scheme in TIPS to balance the occurrence of postoperative complications and effective haemostasis. OBJECTIVE: To construct cirrhotic PH models and compare different shunting schemes in TIPS. METHODS: Three cases of cirrhotic PH with different liver volumes were selected for enhanced computed tomography scanning. The models for different shunting schemes were created using Mimics software, and following FLUENT calculation, all the models were imported into the software computational fluid dynamic-post for processing. In each shunting scheme, the differences in portal vein pressure, hepatic blood perfusion and blood flow from the superior mesenteric vein in the shunt tract were compared. The coefficient G was adapted to evaluate the advantages and disadvantages. RESULTS: (1) Concerning the precise location of the shunt tract, the wider the diameter of the shunt tract, the lower the pressure of the portal vein and the lesser the hepatic blood perfusion. Meanwhile, the pressure drop objective was not achieved with the 6 mm-diameter shunting scheme. (2) The 8 mm-diameter shunting scheme through the left portal vein (LPV) had the highest coefficient G. CONCLUSION: The 8 mm-diameter shunting scheme through the LPV may demonstrate a superior effect and prognosis in TIPS procedures.

Efficacy and Safety of Sharp Recanalization with the Stiff End of a Microguidewire for Treatment of Refractory Central Venous Occlusions in Hemodialysis Patients.

BACKGROUND: Sharp recanalization is a viable procedure for some refractory central venous occlusions that cannot be recanalized with the conventional technique. The sharp recanalization procedures reported in previous studies are often rely on costly devices and with a certain proportion of complications. This study aimed to present an inexpensive and risk-controllable coaxial centrifugally sharp recanalization technique that was independent of any additional costly devices. METHODS: This retrospective study enrolled 8 patients who had received sharp recanalization of central venous occlusions, between August 2017 and May 2021. The sharp recanalization technique was performed centrifugally with the stiff end of a microguidewire after the lesions failed to be passed through with the conventional technique. Clinical data of patients on their lesions, technical success rate, procedure-related complications, and patency rates were collected and analyzed to assess the efficacy and safety of the technique. RESULTS: Technical success was achieved in all patients, with no complications were observed. All symptoms were ameliorated within 48h postsurgery. The median follow-up period was 22 months. All patients maintained patency or assisted patency at 12 month follow-up. CONCLUSIONS: Sharp recanalization performed centrifugally with the stiff end of the microguidewire could be a cost-effective and safe alternative procedure for the treatment of refractory central venous occlusion that cannot be recanalized with conventional technique.

Resensitizing Paclitaxel-Resistant Ovarian Cancer via Targeting Lipid Metabolism Key Enzymes CPT1A, SCD and FASN.

Epithelial ovarian cancer (EOC) is a lethal gynecological cancer, of which paclitaxel resistance is the major factor limiting treatment outcomes, and identification of paclitaxel resistance-related genes is arduous. We obtained transcriptomic data from seven paclitaxel-resistant ovarian cancer cell lines and corresponding sensitive cell lines. Define genes significantly up-regulated in at least three resistant cell lines, meanwhile they did not down-regulate in the other resistant cell lines as candidate genes. Candidate genes were then ranked according to the frequencies of significant up-regulation in resistant cell lines, defining genes with the highest rankings as paclitaxel resistance-related genes (PRGs). Patients were grouped based on the median expression of PRGs. The lipid metabolism-related gene set and the oncological gene set were established and took intersections with genes co-upregulated with PRGs, obtaining 229 co-upregulated genes associated with lipid metabolism and tumorigenesis. The PPI network obtained 19 highly confidential synergistic targets (interaction score > 0.7) that directly associated with CPT1A. Finally, FASN and SCD were up-stream substrate provider and competitor of CPT1A, respectively. Western blot and qRT-PCR results confirmed the over-expression of CPT1A, SCD and FASN in the A2780/PTX cell line. The inhibition of CPT1A, SCD and FASN down-regulated cell viability and migration, pharmacological blockade of CPT1A and SCD increased apoptosis rate and paclitaxel sensitivity of A2780/PTX. In summary, our novel bioinformatic methods can overcome difficulties in drug resistance evaluation, providing promising therapeutical strategies for paclitaxel-resistant EOC via taregting lipid metabolism-related enzymes.

Outcomes of stent grafts for treatment of central venous disease in hemodialysis patients.

BACKGROUND: To evaluate the effectiveness of stent graft (SG) for the treatment of central venous disease (CVD) in hemodialysis patients. METHODS: Between January 2014 and April 2022, 122 patients on hemodialysis with symptomatic CVD were treated with percutaneous transluminal angioplasty (PTA) and bare-metal stent (BMS) or SG placement. The mean follow-up was 14.5 months (IQR: 8.0, 24.2). Patency rates of the target sites were calculated using Kaplan-Meier and log-rank studies. Multivariate Cox proportional hazard models were used to evaluate the association between various characteristics and target site primary patency. RESULTS: Technical success rate was 100%. At 3, 6, 12, and 24 months, the target sites primary patency rates were 86.4%, 74.2%, 45.1%, and 30.4% for PTA; 94.7%, 78.6%, 60.8%, and 45.6% for BMS; and 94.0%, 92.0%, 82.4%, and 66.8% for SG, respectively, and the assisted primary patency rates were 86.5%, 80.4%, 63.8%, and 46.0% for PTA; 94.7%, 89.5%, 77.5%, and 71.1% for BMS; 100%, 100%, 97.8%, and 83.4% for SG, respectively. The Kaplan-Meier analysis indicated that SGs achieved better primary and assisted primary patency than PTA or BMS (p<0.05). SG use and concomitant stenosis were the independent predictors of target site primary patency dysfunction in the multivariate analysis. CONCLUSIONS: This study confirmed the better long-term patency of SG in comparison with PTA and BMS for the treatment of CVD in hemodialysis patients.

Low expression levels of insulin-like growth factor binding protein-3 are correlated with poor prognosis for patients with hepatocellular carcinoma.

Insulin-like growth factor binding protein-3 (IGFBP-3) has previously been identified as a putative tumor suppressor gene. The present study investigated the clinical and prognostic significance of IGFBP-3 expression levels in patients with hepatocellular carcinoma (HCC). Immunohistochemistry (IHC) probing for IGFBP-3 was performed on paraffin-embedded tissue samples obtained from 120 patients with HCC, including tissue samples from 120 primary cancer sites and 50 matched adjacent non-malignant sites. Receiver-operator curve (ROC) analysis was used to determine the cut-off scores for the presence of IGFBP-3-positive tumor cells and to estimate the survival time of the patients. The threshold for marking the positive expression of IGFBP-3 was 65%, based on the area under the ROC. Positive expression of IGFBP-3 was observed in 65/120 (54.2%) of the HCC tissues, and in 36/50 (72%) of the adjacent non-malignant liver tissues. Low levels of IGFBP-3 expression were correlated with tumor size (P=0.003), tumor multiplicity (P=0.044), node (P=0.008), metastasis (P=0.001) and clinical stage (P=0.001), as well as reduced survival time (P=0.015). Using univariate survival analysis, a significant direct correlation between high and low IGFBP-3 expression levels, and patient survival time (mean survival time high IGFBP-3, 39.4 vs. low IGFBP-3, 18.7 months) was identified. Kaplan-Meier analysis demonstrated that IGFBP-3 expression levels and patients survival time were significantly correlated (P<0.001). Multivariate analysis revealed IGFBP-3 expression to be an independent parameter (P=0.003). Therefore, low levels of IGFBP-3 expression are associated with advance clinicopathological classification and may be a predictor of poor survival in patients with HCC. Furthermore, these findings suggest that IGFBP-3 may serve as an independent molecular marker for the evaluation of prognosis in patients with HCC.

Silencing Bag-1 gene via magnetic gold nanoparticle-delivered siRNA plasmid for colorectal cancer therapy in vivo and in vitro.

Apoptosis disorder is generally regarded as an important mechanism of carcinogenesis. Inducement of tumor cell apoptosis can be an effectual way to treat cancer. Bcl-2-associated athanogene 1 (Bag-1) is a positive regulator of Bcl-2 which is an anti-apoptotic gene. Bag-1 is highly expressed in colorectal cancer, which plays a critical role in promoting metastasis, poor prognosis, especially in anti-apoptotic function, and is perhaps a valuable gene target for colorectal cancer therapy. Recently, we applied a novel non-viral gene carrier, magnetic gold nanoparticle, and mediated plasmid pGPH1/GFP/Neo-Bag-1-homo-825 silencing Bag-1 gene for treating colorectal cancer in vivo and in vitro. By mediating with magnetic gold nanoparticle, siRNA plasmid was successfully transfected into cell. In 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, magnetic gold nanoparticle had no significant cytotoxicity and by which delivered RNA plasmid inhibited cell viability significantly (P < 0.05). Downregulation of Bag-1 promoted cell apoptosis (∼47.0 %) in vitro and significantly decreased tumor growth when the cells were injected into nude mice. Based on the studies in vivo, the relative expression of Bag-1 was 0.165 ± 0.072 at mRNA level and ∼60 % at protein level. In further study, C-myc and ß-catenin, mainly molecules of Wnt/ß-catenin pathway, were decreased notably when Bag-1 were silenced in nanoparticle plasmid complex-transfected Balb c/nude tumor xenograft. In conclusion, Bag-1 is confirmed an anti-apoptosis gene that functioned in colorectal cancer, and the mechanism of Bag-1 gene causing colorectal cancer may be related to Wnt/ß-catenin signaling pathway abnormality and suggested that magnetic gold nanoparticle-delivered siRNA plasmid silencing Bag-1 is an effective gene therapy method for colorectal cancer.

Magnetic gold nanoparticle-mediated small interference RNA silencing Bag-1 gene for colon cancer therapy.

Bcl-2-associated athanogene 1 (Bag-1) is a positive regulator of Bcl-2 which is an anti-apoptotic gene. Bag-1 was very slightly expressed in normal tissues, but often highly expressed in many tumor tissues, particularly in colon cancer, which can promote metastasis, poor prognosis and anti-apoptotic function of colon cancer. We prepared and evaluated magnetic gold nanoparticle/Bag-1 siRNA recombinant plasmid complex, a gene therapy system, which can transfect cells efficiently, for both therapeutic effect and safety in vitro mainly by electrophoretic mobility shift assays, flow cytometric analyses, cell viability assays, western blot analyses and RT-PCR (real-time) assays. Magnetic gold nanoparticle/Bag-1 siRNA recombinant plasmid complex was successfully transfected into LoVo colon cancer cells and the exogenous gene was expressed in the cells. Flow cytometric results showed apoptosis rate was significantly increased. In MTT assays, magnetic gold nanoparticles revealed lower cytotoxicity than Lipofectamine 2000 transfection reagents (P<0.05). Both in western blot analyses and RT-PCR assays, magnetic gold nanoparticle/Bag-1 siRNA recombinant plasmid complex transfected cells demonstrated expression of Bag-1 mRNA (P<0.05) and protein (P<0.05) was decreased. In further study, c-myc and ß-catenin which are main molecules of Wnt/ß­catenin pathway were decreased when Bag-1 were silenced in nanoparticle plasmid complex transfected LoVo cells. These results suggest that magnetic gold nanoparticle mediated siRNA silencing Bag-1 is an effective gene therapy method for colon cancer.

The research of nanoparticles as gene vector for tumor gene therapy.

With the development of molecular biology, the application of the gene therapy becomes a tendency in the development of oncotherapy. The gene therapy has been acknowledged as the major progress of modern medicine, also a focus in the oncotherapy research. Commonly vectors of the gene therapy mainly include two categories, namely, viral vectors and nonviral vectors. Nanoparticles gene vector of various different kinds of materials, which belong to non-viral carriers. It presents excellent abilities of adsorption, concentration and protection of DNA, which can be attributed as a main reason of the adsorption and operation of nano-gene vector on exogenous genes. In this article, we mainly reviewed the recent studies of the characteristics of nanoparticles, characteristics and transport mechanism of nanoparticles as gene vector, the progress on nanoparticles as gene vector in tumor gene therapy. Nano-gene vectors, as new drug and gene carriers, present characteristics such as the controlled-release, targeting, and the improvement of bioavailability. Nanoparticles for cancer imaging and therapy have evolved rapidly during the last decade and it is expected that more and more will become clinical practise. In the near future, as a new nanometer gene delivery vector will be in medical research and treatment play a bigger role.

Antiapoptotic gene BAG-1 vector structure of RNA interference and endogenous targeted screening in colon cancer cell lines.

The purposes of the present work were to construct the shRNA plasmids for BAG-1 gene of human and test the expression of mRNA and protein of BAG-1. Recombinant plasmids containing green fluorescent protein reporter genes are constructed using gene cloning methods. The shRNA plasmids for the BAG-1 gene are constructed by RNA interference technology. We applied fluorescent plasmid-transfected target cells in the cell transfection experiments and monitored the transfection rate of plasmids by observing the fluorescence amount. We transfected three synthesized shRNA in target screening cell and adopted RT-PCR and Western test to identify the difference of target gene transfection and translation level in cells. The specific shRNA plasmid for the BAG-1 gene was successfully recombined, and stably transfected colon cancer Lo Vo cell lines were obtained. The results present that the constructed shRNA plasmids significantly inhibited the expression of mRNA and protein of Lo Vo cell BAG-1, and can maintain the effect for a long term. pGPH1/GFP/Neo-BAG-1-homo-825 was screened as the optimum sequence of interference so as to lay a solid foundation to explore into the research on the BAG-1 gene and the biological behavior of colon cancer cells. It showed the remarkable advantage of RNAi in the generation of posttranscriptional gene silencing.