A novel link between circPDE3B and ferroptosis in esophageal squamous cell carcinoma progression.

AIM: To unravel whether ferroptosis involves with the actions by circPDE3B-mediated facilitation of esophageal squamous cell carcinoma (ESCC) progression. METHODS: Human ESCC tissues and cell lines were prepared for the evaluation of ferroptosis. Cellular iron, ROS, GSH, and MDA levels were measured to assess ferroptosis. Flow cytometry was employed to analyze apoptosis and cell cycle. Subcellular fractionation and fluorescence in situ hybridization (FISH) were conducted to validate the localization of circPDE3B. RNA pull-down, RNA immunoprecipitation (RIP), and luciferase assay were subjected to identify the molecular mechanisms. Nude mouse xenograft model was carried out to evaluate the function of circPDE3B/SLC7A11/CBS in vivo. RESULTS: Increased circPDE3B in human ESCC specimens was positively correlated with ferroptosis-related molecules, SLC7A11 and CBS. Functionally, circPDE3B knockdown triggered ferroptosis, apoptosis, and cell cycle arrest in ESCC cells. Whereas, these effects were obviously blocked by miR-516b-5p inhibitor. Mechanistically, not only circPDE3B sponged miR-516b-5p to upregulate CBS, but also directly bound with HNRNPK to stabilize SLC7A11. In mice, depletion of circPDE3B restrained ESCC growth, while this was abolished by overexpression of CBS or SLC7A11. CONCLUSION: In summary, circPDE3B promotes ESCC progression by suppressing ferroptosis through recruiting HNRNPK/SLC7A11 and miR-516b-5p/CBS axes.

Expression And Prognostic Role of PRDX1 In Gastrointestinal Cancers.

Esophageal, gastric, liver, and colorectal cancers represent four prevalent gastrointestinal cancers that pose substantial threats to global health due to their high morbidity and mortality rates. Peroxiredoxin 1 (PRDX1), a significant component of the PRDXs family, primarily functions to counteract the peroxides produced by metabolic activities in the body, thereby maintaining the dynamic equilibrium of peroxides in vivo. Intriguingly, PRDX1 expression correlates strongly with cancer's onset, progression, and prognosis. This study mainly applied bioinformatics methods to analyze PRDX1's expression, diagnosis, and prognosis in gastrointestinal cancers and to summarize current research advancements. Evidence from the bioinformatics database suggested that the high expression of PRDX1 was a prominent characteristic of these four gastrointestinal cancers, with this observation reaching statistical significance. The high expression of PRDX1 in gastrointestinal cancer cells also confirms this result. Notably, the primary alteration in PRDX1 within these cancers is the presence of genetic mutations. PRDX1 demonstrated the highest diagnostic efficacy for colorectal cancer. Nevertheless, elevated PRDX1 levels only significantly diminished the survival time of liver cancer patients, exerting no statistically significant impact on the survival duration of patients afflicted by the other three types of gastrointestinal cancers. Recent research has indicated variability in PRDX1 expression across different cancer types, with high expression being predominantly observed in these four gastrointestinal cancers and, in most instances, unfavorable prognosis. These findings broadly align with the results derived from bioinformatics. This research underscores the high expression of PRDX1 in gastrointestinal cancers, its relevance to the diagnosis and prognosis monitoring of these cancers, and its potential to guide clinical treatment for these cancers.

Effects of autophagy­related gene 5 on tumor development and treatment (Review).

Autophagy is a fundamental cellular metabolic process, whose main role is to remove excess or damaged organelles and maintain the normal structural state of cells. Autophagy­related gene 5 (ATG5) is one of the important genes involved in cellular autophagy, which is widely expressed in tissues and cells and connected to various signaling pathways. It is involved in the regulation of cell proliferation, invasion and migration as well as the tumor immune microenvironment, which affects the resistance to radiotherapy and chemotherapy, as well as the overall survival of tumor patients. Recently, many studies have confirmed that ATG5 plays a double­edged sword role on tumors, as it can play not only pro­tumor but also tumor­suppressive roles. However, its role in tumor treatment has not been systematically summarized. Therefore, this paper provides a systematic summary of the basic functions of ATG5, its role in the development and treatment of tumors and potentially give some ideas for clinical treatment of tumors.

A Nomogram to Predict the Risk of Stent Dysfunction After TIPS in Patients with Hepatitis B Cirrhosis.

RATIONALE AND OBJECTIVES: To develop and validate a nomogram for the prediction of stent dysfunction after transjugular intrahepatic portosystemic shunt (TIPS) placement in patients with hepatitis B cirrhosis. MATERIALS AND METHODS: From 2012 to 2020, 355 patients with hepatitis B cirrhosis who underwent TIPS placements were enrolled in this study. A multivariable logistic regression analysis was applied to determine independent risk factors for the nomogram construction. Discrimination, calibration, and clinical usefulness of the prediction model were assessed by using receiver operating characteristic curves, calibration scatter plots, and a decision curve analysis (DCA). RESULTS: Independent factors for TIPS stent dysfunction included diabetes, previous splenectomy, the shunting branch of the portal vein, and stent position, which were used to construct the nomogram. The AUC values in the training and validation cohorts were 0.817 (95% CI: 0.731-0.903) and 0.804 (95% CI: 0.673-0.935), respectively, which suggested a good predictive ability. The calibration curves in both cohorts revealed good agreement between the predictions and actual observations. The DCA curve indicated that when the threshold probability ranged from 2% to 88%, the nomogram could provide clinical usefulness and a net benefit. CONCLUSION: The nomogram that we developed could be conveniently used to predict TIPS stent dysfunction in patients with hepatitis B cirrhosis.

Percutaneous transluminal stenting for superior vena cava syndrome caused by malignant tumors: a single-center retrospective study.

OBJECTIVES: To evaluate the efficacy of percutaneous stent placement in the treatment of superior vena cava syndrome caused by malignant tumors. METHODS: We retrospectively analyzed the clinical data of 32 patients with superior vena cava syndrome who underwent percutaneous endovascular stent treatment in our department from 2015 to 2019 due to malignant tumors and summarized the patient's sex, age, tumor type, endovascular treatment plan, complications and postoperative follow-up. RESULTS: All patients successfully underwent percutaneous intraluminal stent placement with digital subtraction angiography (DSA). Thirty-seven endovascular stents were implanted in 32 patients, including 21 Eluminexx stents, 12 Wallstent stents and 4 covered stents. The technical success rate was 100%, and there were no serious surgery-related complications. The remission rate of clinical symptoms was 53.1% (17/32) at 24 h and 84.4% (27/32) at 48 h. After 48 h, the symptoms of the remaining patients were slowly relieved, and the symptom relief rate was 100% at 7 days. The follow-up period was 1.5-24 months, with an average follow-up period of 6.5 months. During the follow-up, 3 patients had restenosis and 1 patient had secondary thrombosis in the stent. Their symptoms were relieved after the second treatment. CONCLUSION: For superior vena cava syndrome caused by malignant tumors, percutaneous endoluminal stent therapy can quickly and effectively relieve the clinical symptoms of patients, and the incidence of complications is low.

Clinical study of transjugular intrahepatic portosystemic shunt combined with AngioJet thrombectomy for acute portal vein thrombosis in non-cirrhosis.

ABSTRACT: To evaluate the outcomes of the transjugular intrahepatic portosystemic shunt (TIPS) combined with AngioJet thrombectomy in patients with noncirrhotic acute portal vein (PV) thrombosis.Retrospective analysis from January 2014 to March 2017, 23 patients underwent TIPS combined with AngioJet thrombectomy for acute PV thrombosis in noncirrhosis. The rates of technical success, the patency of the PV, liver function changes, and complications were evaluated.Twenty-three patients underwent combined treatment, with a technical success rate of 100%. Twenty-four hours after treatment, PV thrombosis grade was improved significantly (P = .001). Before and after treatment, Albumin (gm/dl), aspartate transaminase (IU/l), alanine transaminase (IU/l), and platelets (109/L) were all significantly improved (P < .05). Minor complications include hematoma, hematuria, and hepatic encephalopathy. After 1 week of treatment, computed tomography scan revealed 8.7% (2/23) cases of hepatic envelope hematoma (thickness less than 2 cm). Hemoglobinuria occurred in 18/23 (78.3%) patients after treatment and returned to normal within 1 to 2 days. Two patients 2/23 (8.7%) had transient grade I encephalopathy after TIPS. The 1-year overall survival rate was 100% (23/23). No major complications during treatment in all patientsAngioJet thrombectomy via TIPS has a favorable short-term effect in clearing thrombus and alleviating symptoms in diffuse acute PVT. The long-term efficacy of this treatment needs to be further studied.

Sequential interventional therapy for Budd-Chiari syndrome associated with fresh inferior vena cava thrombosis.

OBJECTIVE: Our study aimed to evaluate the safety and efficacy of sequential interventional therapy for Budd-Chiari syndrome (BCS) caused by obstruction of the inferior vena cava (IVC) with fresh thrombus in the IVC. METHODS: Full medical records were obtained for 20 patients with BCS associated with fresh IVC thrombus who received sequential interventional therapy from 2014 to 2019 at our hospital. All patients underwent small-diameter percutaneous transluminal angioplasty (PTA) balloon catheter predilation combined with sequential catheter-directed thrombolysis and large-diameter PTA balloon dilation. Ultrasound examinations were performed at 1 week, 1 month, 3 months, and every 6 months thereafter. Therapeutic effects and perioperative and postoperative adverse effects were recorded to assess the safety of the treatment. RESULTS: All 20 patients were treated with small PTA balloon catheters (diameter, 10-14 mm) to predilate the occlusive segment of the IVC. Urokinase 400,000 to 600,000 (465,000 ± 93,000) units was administered to patients through the catheter for 6 to 20 (9.7 ± 4.2) consecutive days postoperatively. Ultrasound re-examination showed that the IVC thrombus disappeared completely in 14 patients (70.0%), and a small amount of the old thrombus remained in 6 patients (30.0%). After thrombolysis, all 20 patients received PTA balloon dilation (diameter, 26-30 mm) in the stenosed IVC segment, and blood flow recovered subsequently. No pulmonary embolism or death occurred in the perioperative course. The perioperative survival rate was 100.0%. CONCLUSIONS: Sequential interventional therapy for BCS associated with fresh IVC thrombus is safe and effective.

CLK3 Is A Direct Target Of miR-144 And Contributes To Aggressive Progression In Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer with high incidence. The underlying molecular mechanisms of HCC development have been intensively studied. CLK3 (CDC Like Kinase 3) is a nuclear dual-specificity kinase and regulates gene splicing. We investigated the expression profile and functional role of CLK3 in HCC. METHODS: Immunohistochemistry (IHC) and Western blot were performed to determine CLK3 expression in HCC tissues. Bioinformatics analysis using TCGA and GEO database was conducted to evaluate the relationship between CLK3 expression and HCC prognosis. Cell proliferation was assessed by CCK8, EdU and colony formation assays, while transwell and wound-healing assays were performed to investigate the cell migration and invasion in vitro. Xenograft nude mouse model was used to test the function of CLK3 on tumor growth in vivo. Luciferase reporter assay, Western blot and RT-qPCR were conducted to verify the miRNA that directly targeted CLK3. RESULTS: CLK3 was markedly upregulated in HCC tissues, and the expression levels of CLK3 were closely associated with TNM stages and HCC prognosis. Functional analysis indicated that knockdown of CLK3 could suppress HCC cell growth, invasion and migration in vitro, and inhibit tumor development in vivo. Moreover, CLK3 was demonstrated as a direct target of miR-144 and miR-144 expression was inversely correlated with CLK3 expression in HCC. Enforced overexpression of miR-144 markedly inhibited the CLK3 expression while overexpression of CLK3 partially reversed the inhibitory function of miR-144 on HCC cell growth and metastasis. Mechanistically, we found that miR-144 overexpression inhibited Wnt/ß-catenin signaling and the inhibition could be partly abolished by overexpression of CLK3. CONCLUSION: In summary, we demonstrate tumor suppressor miR-144 suppresses hepatocellular carcinoma development and metastasis via regulating CLK3 and Wnt/ß-catenin signaling, indicating that miR-144/CLK3 could be used for HCC diagnosis and treatment.

Long noncoding RNA CASC15 predicts unfavorable prognosis and exerts oncogenic functions in non-small cell lung cancer.

BACKGROUND: Aberrant expression of long non-coding RNA cancer susceptibility 15 (lncRNA CASC15) has been documented in various human tumors, and upregulation of CASC15 is closely correlated with cancer progression. However, the expression profile and potential biological functions of lncRNA CASC15 in non-small cell lung cancer (NSCLC) have not been fully characterized. METHODS: The expression levels of CASC15 were assessed by qRT-PCR in human NSCLC tissues and by in situ hybridization in NSCLC tissue microarray. The relationship between CASC15 expression and clinical parameters, as well as prognosis were analyzed and validated in TCGA NSCLC datasets. The biological functions of CASC15 were analyzed by CCK-8 assay, cell migration and invasion assay in NSCLC cell lines in vitro. In addition, a mouse xenograft model was established to evaluate the effect of CASC15 knockdown on NSCLC tumor growth in vivo. Epithelial-mesenchymal transition (EMT) related molecules were examined by western blot and immunohistochemistry staining. RESULTS: We found that CASC15 was upregulated in NSCLC tissues and cell lines. High expression levels of CASC15 were correlated with malignancies and poor survival rate in NSCLC patients. Multivariate analysis revealed that CASC15 was an independent risk factor of prognosis. In addition, we demonstrated that CASC15 knockdown inhibited NSCLC cell proliferation, migration and invasion in vitro. Xenograft model showed CASC15 knockdown significantly suppressed NSCLC tumor growth. Mechanistically, we revealed that CASC15 regulated EMT-related molecules and promoted the NSCLC progression and metastasis. CONCLUSION: In summary, our findings suggest CASC15 exhibits an oncogenic role in promoting NSCLC tumorigenesis via regulating EMT.

Perilipin 5 deficiency promotes atherosclerosis progression through accelerating inflammation, apoptosis, and oxidative stress.

Excessive plasma triglyceride (TG) and cholesterol levels promote the progression of several prevalent cardiovascular risk factors, including atherosclerosis, which is a leading death cause. Perilipin 5 (Plin5), an important perilipin protein, is abundant in tissues with very active lipid catabolism and is involved in the regulation of oxidative stress. Although inflammation and oxidative stress play a critical role in atherosclerosis development, the underlying mechanisms are complex and not completely understood. In the present study, we demonstrated the role of Plin5 in high-fat-diet-induced atherosclerosis in apolipoprotein E null (ApoE-/- ) mice. Our results suggested that Plin5 expressions increased in the artery tissues of ApoE-/- mice. ApoE/Plin5 double knockout (ApoE-/- Plin5-/- ) exacerbated severer atherogenesis, accompanied with significantly disturbed plasma metabolic profiles, such as elevated TG, total cholesterol, and low-density lipoprotein cholesterol levels and reduced high-density lipoprotein cholesterol contents. ApoE-/- Plin5-/- exhibited a higher number of inflammatory monocytes and neutrophils, as well as overexpression of cytokines and chemokines linked with an inflammatory response. Consistently, the IκBα/nuclear factor kappa B pathway was strongly activated in ApoE-/- Plin5-/- . Notably, apoptosis was dramatically induced by ApoE-/- Plin5-/- , as evidenced by increased cleavage of Caspase-3 and Poly (ADP-ribose) polymerase-2. In addition, ApoE-/- Plin5-/- contributed to oxidative stress generation in the aortic tissues, which was linked with the activation of phosphatidylinositol 3-kinase/protein kinase B and mitogen-activated protein kinases pathways. In vitro, oxidized low-density lipoprotein (ox-LDL) increased Plin5 expression in RAW264.7 cells. Its knockdown enhanced inflammation, apoptosis, oxidative stress, and lipid accumulation, while promotion of Plin5 markedly reduced all the effects induced by ox-LDL in cells. These studies strongly supported that Plin5 could be a new regulator against atherosclerosis, providing new insights on therapeutic solutions.

MicroRNA-451 inhibits vascular smooth muscle cell migration and intimal hyperplasia after vascular injury via Ywhaz/p38 MAPK pathway.

Increasing evidence has indicated that intimal hyperplasia is a common event in the pathophysiology of many vascular diseases including atherosclerosis (AS). Recently, deregulated microRNAs (miRNAs) have been reported to be associated with the pathophysiology of AS. However, the biological function and regulatory mechanisms of miRNAs in intimal hyperplasia in AS remain largely unclear. The aim of this study was to investigate the effects of miRNAs on intimal hyperplasia and reveal the underlying mechanisms of their effects. Firstly, the model of rat vascular injury was successfully constructed in vivo. Then, the miRNAs expression profiles were analyzed by miRNA microarray. It was observed that miR-451 was significantly downregulated in injury carotid arteries. Subsequently, we investigated miR-451 function and found that upregulation of miR-451 by agomir-451 improves intimal thickening in rats following vascular injury. It was also observed that miR-451 was downregulated in the VSMCs following platelet-derived growth factor type BB (PDGF-BB) stimulation. The upregulation of miR-451 attenuated PDGF-BB-induced VSMCs injury, as evidenced by inhibition of proliferation, invasion and migration. Besides, overexpression of miR-451 blocked the activation of p38 MAPK signaling pathway in PDGF-BB treated VSMCs, as demonstrated by the downregulation of phosphorylated (p-) p38. In addition, Ywhaz, a positive regulator of p38 MAPK signaling pathway, was found to be a direct target of miR-451 in the VSMCs and this was validated using a luciferase reporter assay. Overexpression of Ywhaz partially abolished the inhibitory effects of miR-451 overexpression on PDGF-BB induced VSMCs injury. Collectively, these findings indicated that miR-451 protected intimal hyperplasia and PDGF-BB-induced VSMCs injury by Ywhaz/p38 MAPK pathway, and miR-451 may be considered as a potential therapeutic target in the treatment of AS.

Long-Term Outcomes of Endoluminal Sharp Recanalization of Occluded Inferior Vena Cava in Budd-Chiari Syndrome.

PURPOSE: To report the long-term results of endoluminal sharp recanalization of occluded inferior vena cava (IVC) in patients with the Budd-Chiari syndrome (BCS). PATIENTS AND METHODS: Seventy-two consecutive patients with BCS and IVC occlusion underwent endoluminal recanalization of the IVC occlusion during a 6-year period. BCS with occlusive IVC was detected by reviewing patient history and color Doppler ultrasonography. Data on technical success, morbidity, mortality, complications, and color Doppler sonographic outcome were collected and analyzed. RESULTS: Seventy-seven recanalizations were performed in 72 patients. Technical success (patent IVC with good blood flow) was achieved in 70 (97.4%) patients. No perioperative death was observed. Six complications were found during recanalization, and 10 complications were found for total interventional procedures. The complication rates were 7.8% and 7.3% for recanalization and total procedure, respectively. Bleeding of access veins was the most common complication, and 2 patients showed slight rupture of IVC. The postoperative IVC diameter and blood speed of IVC increased significantly. Fifty-seven patients (79.2%) were clinical cured, and 2 patients (2.8%) showed no improvement. The 1-year, 3-year, and 5-year primary patency rates were 92.5%, 86.8%, and 77.3%, respectively. The second patency rates were 100.0%, 97.8%, and 91.8% for 1, 3, and 5 years, respectively. There were 2 deaths during follow-up. CONCLUSION: Endoluminal sharp recanalization of occluded IVC in patients with BCS is safe and effective with good long-term outcomes.

Excellent long-term outcomes of endovascular treatment in budd-chiari syndrome with hepatic veins involvement: A STROBE-compliant article.

This study aimed to evaluate the long-term efficacy and safety of percutaneous transhepatic balloon angioplasty (PTBA) and transjugular intrahepatic portosystemic stent-shunt (TIPSS) in the treatment of Budd-Chiari syndrome (BCS) with hepatic veins involvement. Between June 2008 and August 2016, a total of 60 BCS patients with hepatic vein involvement in our department were enrolled in this study. Thirty-three cases underwent hepatic vein balloon angioplasty in PTBA Group and 27 cases underwent TIPSS. Data were retrospectively collected, and follow-up observations were performed. TIPSS Group showed significantly higher thrombotic/segmental obstruction and peripheral stenosis/obstruction compared with PTBA Group. The success rates were 93.9% and 100.0% in PTBA Group and TIPSS Group, respectively. The mean portal vein pressure decreased significantly after stenting. Except for 1 patient died from repeated hemorrhage, other sever complications had not been observed in both group. Twenty-six patients and 21 patients were clinically cured in PTBA Group and TIPSS Group, respectively. The primary patency rates were 89.7%, 79.3%, and 79.3% for short-term, mid-term and longterm in PTBA Group, which were significantly higher than TIPSS Group for long-term follow up. The second patency rates were 100.0%, 96.6% and 96.6% for short-term, mid-term and long-term in PTBA Group, which were similar to TIPSS Group (P = 1.0000). In conclusion, PTBA and TIPSS are safe and effective in the treatment of BCS with hepatic veins involvement, with an excellent long-term patency rate of hepatic vein and TIPSS shunt. TIPSS can be used to treat patients with all 3 hepatic veins lesion and failure PTBA.

Percutaneous Transhepatic Hepatic Vein Angioplasty in Budd-Chiari Syndrome After Transvenous Failure.

PURPOSE: To evaluate the safety and efficacy of percutaneous transhepatic route creation for hepatic vein (HV) angioplasty in Budd-Chiari syndrome (BCS). PATIENTS AND METHODS: Between April 2012 and August 2016, a total of 19 BCS patients underwent percutaneous transhepatic route creation for HV angioplasty after transvenous catheterization failure in this study. Color Doppler ultrasonography was required in all patients after admission and during follow-up. Data were retrospectively collected, and follow-up observations were performed. RESULTS: Technical and clinical success was achieved in 18 patients. Except for 1 failure of route creation, 19 routes were successfully created in 18 patients, with a technology success rate of 95.0%. Twenty-two balloon angioplasties were performed in 18 patients, with a mean balloon diameter of 13.6 ± 0.5 mm. Blood pressure and length of occlusive HV decreased significantly, and blood flow velocity and diameter of HV increased significantly after procedure. Abdominal distension/pain and ascites decreased significantly after procedure. One procedure-related death occurred, who died of gastrointestinal bleeding 6 days later. Except for the failure case, the rest of 18 patients were successfully followed up. The remaining 18 patients survived during follow-up, with a 5-year survival rate of 94.9%. One patient had a restenosis of HV after 47 days, and had undergone successful dilation. The 5-year primary and second patency rates were 94.1% and 100%, respectively. CONCLUSION: Percutaneous transhepatic route creation is safe and effective for HV angioplasty, and can be used to treat BCS patients after transvenous catheterization failure.

Overexpression of Sirtuin2 prevents high glucose-induced vascular endothelial cell injury by regulating the p53 and NF-κB signaling pathways.

OBJECTIVES: To investigate the potential role and underlying mechanism of Sirtuin2 (SIRT2) in regulating high glucose (HG)-induced vascular endothelial cell injury by using human umbilical vein endothelial cells (HUVECs). RESULTS: SIRT2 mRNA and protein expression levels were decreased in HG-treated HUVECs. SIRT2 overexpression increased viability, decreased apoptosis and reduced levels of reactive oxygen species in HG-treated HUVECs. SIRT2 overexpression decreased TNF-α expression (146.5 ± 22.8 pg TNF-α ml-1) relative to that in the empty vector group (263.5 ± 18.5 pg TNF-α ml-1) and decreased MCP-1 expression (63.8 ± 9.85 pg MCP-1 ml-1) relative to that in the empty vector group (105.8 ± 8.5 pg MCP-1 ml-1). SIRT2 overexpression decreased the acetylation of p53 by 33% and decreased the acetylation of NF-κB p65 by 58% in HG-treated HUVECs. CONCLUSION: SIRT2 prevents HG-induced vascular endothelial cell injury through suppressing the p53 and NF-κB signaling pathways.

Plin5 deficiency promotes atherosclerosis progression through accelerating inflammation, apoptosis and oxidative stress.

Excessive plasma triglyceride and cholesterol levels promote the progression of several prevalent cardiovascular risk factors, including atherosclerosis, which is a leading death cause. Perilipin 5 (Plin5), an important perilipin protein, is abundant in tissues with very active lipid catabolism, and is involved in the regulation of oxidative stress. Although, in?ammation and oxidative stress play a critical role in atherosclerosis development, the underlying mechanisms are complex and not completely understood. In the present study, we demonstrated the role of Plin5 in high-fat-diet-induced atherosclerosis in apolipoprotein E null (ApoE-/- ) mice. Our results suggested that Plin5 expressions increased in the artery tissues of ApoE-/- mice. ApoE/Plin5 double knockout (ApoE-/- Plin5-/- ) exacerbated severer atherogenesis, accompanied with significantly disturbed plasma metabolic profiles, such as elevated triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) levels and reduced high-density lipoprotein cholesterol (HDLC) contents. ApoE-/- Plin5-/- exhibited higher number of inflammatory monocytes and neutrophils, as well as over-expression of cytokines and chemokines linked with inflammatory response. Consistently, IκBα/nuclear factor kappa B (NF-κB) pathway was strongly activated in ApoE-/- Plin5-/- . Notably, apoptosis was dramatically induced by ApoE-/- Plin5-/- , as evidenced by increased cleavage of Caspase-3 and Poly (ADP-ribose) polymerase-2 (PARP-2). In addition, ApoE-/- Plin5-/- contributed to oxidative stress generation in the aortic tissues, which was linked with the activation of phosphatidylinositol 3-kinase /protein kinase B (PI3K/AKT) and mitogen-activated protein kinases (MAPKs) pathways. In vitro, oxidized low-density lipoprotein (oxLDL) increased Plin5 expression in RAW264.7 cells. Its knockdown enhanced inflammation, apoptosis, oxidative stress and lipid accumulation, while promotion of Plin5 markedly reduced all the effects induced by ox-LDL in cells. These studies strongly supported that Plin5 could be a new regulator against atherosclerosis, providing new insights on therapeutic solutions. This article is protected by copyright. All rights reserved.

Detection and characterization of Budd-Chiari syndrome with inferior vena cava obstruction: Comparison of fixed and flexible delayed scan time of computed tomography venography.

PURPOSE: To compare the results of computed tomography venography (CTV) with a fixed and a flexible delayed scan time for Budd-Chiari syndrome (BCS) with inferior vena cava (IVC) obstruction. MATERIAL AND METHODS: A total of 209 consecutive BCS patients with IVC obstruction underwent either a CTV with a fixed delayed scan time of 180s (n=87) or a flexible delayed scan time for good image quality according to IVC blood flow in color Doppler ultrasonography (n=122). The IVC blood flow velocity was measured using a color Doppler ultrasound prior to CT scan. Image quality was classified as either good, moderate, or poor. Image quality, surrounding structures and the morphology of the IVC obstruction were compared between the two groups using a χ2-test or paired or unpaired t-tests as appropriate. Inter-observer agreement was assessed using Kappa statistics. RESULTS: There was no significant difference in IVC blood flow velocity between the two groups. Overall image quality, surrounding structures and IVC obstruction morphology delineation on the flexible delayed scan time of CTV images were rated better relative to those obtained by fixed delayed scan time of CTV images (p<0.001). Evaluation of CTV data sets was significantly facilitated with flexible delayed scan time of CTV. There were no significant differences in Kappa statistics between Group A and Group B. CONCLUSION: The flexible delayed scan time of CTV was associated with better detection and more reliable characterization of BCS with IVC obstruction compared to a fixed delayed scan time.

Budd-Chiari syndrome with upper gastrointestinal hemorrhage: Characteristic and long-term outcomes of endovascular treatment.

Purpose To identify the characteristics and evaluate the long-term outcomes of endovascular treatment of Budd-Chiari syndrome with upper gastrointestinal hemorrhage. Methods Forty-seven consecutive Budd-Chiari syndrome patients with upper gastrointestinal hemorrhage were referred for the treatment with percutaneous transluminal balloon angioplasty, and subsequently underwent follow-up. Data were retrospectively collected and follow-up observations were performed at 1, 2, 2-5, and 5-8 years postoperatively. Results Cirrhosis was presented in 16 patients, and splenoportography reviewed obvious varices in 18 patients. Percutaneous transluminal balloon angioplasty was technically successful in all patients. Major procedure-related complications occurred in 3 of the 47 patients (6.38%). The cumulative 1, 2, 2-5, and 5-8 year primary patency rates were 100% (46/46), 93.2% (41/44), 90.9% (40/44), and 86.4% (19/22), respectively. The cumulative 1, 2, 2-5, and 5-8 year secondary patency rates were 100% (47/47), 100% (44/44), 100% (44/44), and 95.5% (21/22), respectively. Mean and median duration of primary patency was 65.17 ± 3.78 and 69.0 ± 5.69 months, respectively. No upper gastrointestinal hemorrhage recurred during follow-ups. The mean survival time was 66.97 ± 3.61 months and the median survival time was 69.0 ± 4.10 months. Conclusion PTBA was an effective treatment that can prevent recurrence of the life-threatening complications and ensured long-term satisfactory clinical outcomes for Budd-Chiari syndrome patients with upper gastrointestinal hemorrhage. Percutaneous transhepatic variceal embolization was not recommended for all Budd-Chiari syndrome patients with upper gastrointestinal hemorrhage.

Endovascular Treatment of an Unusual Membranous Obstruction of the Inferior Vena Cava in Budd-Chiari Syndrome Complicated by Mural Portal Vein Thrombosis.

We describe the case of a patient with Budd-Chiari syndrome who presented with an unusual membranous obstruction of the inferior vena cava complicated by massive portal vein thrombosis (PVT). The patient underwent percutaneous transluminal balloon angioplasty through the right groin and was prescribed oral warfarin for 6 months. Treatment resulted in the complete disappearance of the PVT. This therapeutic strategy should be considered in the management of other cases of this rare, complex disease.

Value of blood flow velocity on color Doppler ultrasonography for optimization of delay in scanning time on computed tomography venography in patients with Budd-Chiari syndrome and inferior vena cava obstruction.

PURPOSE: To prospectively determine the value of blood flow velocity in the inferior vena cava (IVC) on color Doppler ultrasonography for the optimization of the delay in scanning time after contrast injection during computed tomography (CT) venography in patients with Budd-Chiari syndrome (BCS) with IVC obstruction. METHODS: We enrolled 122 consecutive BCS patients with IVC obstruction. All patients underwent color Doppler ultrasonography, CT venography, and digital subtraction angiography (DSA) in that order prior to treatment. The delay in scanning time during CT venography was set at 120, 180, 240, and 300 s after contrast injection. The correlation between delay in CT scanning and IVC blood flow velocity on color Doppler ultrasonography was explored. Image quality was classified as good, moderate, or poor. Patients with good CT image quality were considered to have an optimal delay in scanning time. RESULTS: Delays in scanning time of 120, 180, 240, and 300 s yielded good-quality images in 2, 7, 49, and 64 patients, respectively. The corresponding IVC blood flow velocities in these patients were 16.10 ± 0.42 cm/s (range 15.8-16.4 cm/s), 12.90 ± 1.58 cm/s (range, 11-15 cm/s), 7.53 ± 1.35 cm/s (range 5-10 cm/s), and 1.95 ± 1.75 cm/s (range 0-5.5 cm/s). CONCLUSION: IVC blood flow velocity on color Doppler ultrasonography could serve as a useful tool for the optimization of the delay in scanning time during CT venography to ensure good-quality images for the diagnosis of BCS with IVC obstruction.