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.

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.

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.

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.

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.

Flat detector C-arm CT-guidance system in performing percutaneous transthoracic needle biopsy of small (≤3 cm) pulmonary lesions.

BACKGROUND: Nowadays, flat detector (FD) equipped angiographic C-arm computed tomography (CACT) systems can be used to acquire CT-like cross-sectional images directly within the interventional suite. The CACT systems offer real time visualization of transthoracic needle biopsy (TNB) procedure and more flexibility in the orientation of the detector system around the patient compared to traditional CT systems. PURPOSE: To evaluate the value of a flat detector C-arm CT-guidance system in performing percutaneous transthoracic needle biopsy (PTNB) for small (≤3 cm) pulmonary lesions in clinical practice. MATERIAL AND METHODS: A total of 60 patients with solid lung lesions were retrospectively enrolled to undergo PTNB procedures. The mean diameter of lesions was 2.3 ± 0.6 cm (range, 0.6-3 cm). The needle path was carefully planned and calculated on the C-arm CT system, which acquired three-dimensional CT-like cross-sectional images. The PTNB procedures were performed under needle guidance with fluoroscopic feedbacks. RESULTS: Histopathologic tissue was successfully obtained from 59 patients with a puncture success rate of 98.3% (59/60). The diagnostic accuracy rate was found to be 91.5% (54/59). There were only two cases of pneumothorax (3.3%) requiring therapy. The rates of pneumothorax and hemoptysis were low (15.0% [9/60] and 8.3% [5/60], respectively). The overall procedural time was in the range of 12-18 min, resulting in a mean exposure dose of 224.4 ± 4.8 mGy. CONCLUSION: Our study shows that C-arm CT-based needle guidance enables reliable and efficient needle positioning and progression by providing real-time intraoperative guidance for small (≤3 cm) pulmonary lesions in clinical practice.

Spontaneous intrahepatic portosystemic shunt in Budd-Chiari syndrome.

Budd-Chiari syndrome (BCS) caused by hepatic venous outflow obstruction may result in portal hypertension and the development of intrahepatic collaterals that bypass the obstruction. Spontaneous intrahepatic portosystemic venous shunt (SIPSVS) is uncommon and may be associated with portal hypertension. SIPSVS is extremely rare in patients with BCS and has not been well documented. We report a case of SIPSVS in a 42-year-old woman with BCS caused by membranous obstruction and chronic thrombosis in the inferior vena cava (IVC). A direct vascular communication between the left portal vein and IVC was confirmed by sonography and a computed tomography angiography scan. The patient underwent successful percutaneous balloon angioplasty of the IVC. Surgical or endovascular treatment for SIPSVS was not carried out because the patient was asymptomatic and remained asymptomatic in terms of encephalopathy at a 1-year follow-up.

Endovascular treatment of an unusual primary arterioportal fistula complicated by cavernous transformation of the portal vein caused by portal thrombosis.

We describe an elderly woman who presented with an unusual primary arterioportal fistula and cavernous transformation of the portal vein caused by portal thrombosis, which were subsequently managed with endovascular coil embolization and transjugular intrahepatic portosystemic shunt using 2 stents after balloon remodeling. This case shows a rarely seen condition in the elderly and a novel management strategy that should be considered in the management of this complex disease.

Endovascular treatment for extrahepatic portal vein bifurcation stenosis after a Whipple procedure using the kissing stents technique.

A 57-year-old man presented with a rare extrahepatic portal vein bifurcation scar stenosis involving the proximal splenic vein and superior mesenteric vein after a Whipple procedure. He was treated with endovascular coil embolization for the gastroesophageal varices and kissing stents for the portal vein bifurcation stenosis. This case illustrates a rarely seen complication after the Whipple procedure and a novel management strategy that can be considered in the management of this complex disease.

Assessment of 64-row computed tomographic angiography for diagnosis and pretreatment planning in pulmonary sequestration.

PURPOSE: This study was done to evaluate the clinical implications and results of a prospective protocol using 64-row computed tomographic angiography (CTA) for diagnosis and pre-treatment planning in pulmonary sequestration (PS). MATERIALS AND METHODS: Forty-five patients with suspected PS were referred for CTA examination. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of measures used to detect PS were determined by patient-based and aberrant systemic artery-based evaluations. The location, the size and the number of aberrant systemic arteries, and the feasibility of endovascular treatment were analysed. The capability of CTA to provide a working view and the accuracy of measurements in choosing a coil were also assessed. RESULTS: Digital subtraction angiography and/or surgery revealed PS in 38 patients, and 7 patients had no PS. The patient-based evaluation yielded an accuracy of 97.8 %, sensitivity of 97.4 %, specificity of 100 %, PPV of 100 % and NPV of 87.5 %, in the detection of PS. CTA clearly depicted the PS in all 38 patients, and the aberrant systemic artery was accurately demonstrated in 37 out of 38 patients where endovascular treatment was possible. Working views for endovascular treatment were found in all patients with PS, and the choice of coil was correct in 37 out of 38 patients using CTA. CONCLUSIONS: 64-row CTA appears to be effective in terms of supporting accurate diagnosis and pre-treatment planning in PS. CTA is not only able to provide clear visualisation of aberrant systemic arteries but also provides detailed images of abnormal lung parenchyma and the airways.

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.

Circular RNA hsa_circ_0000277 sequesters miR-4766-5p to upregulate LAMA1 and promote esophageal carcinoma progression.

Growing evidence has indicated that circular RNAs (circRNAs) play a pivotal role as functional RNAs in diverse cancers. However, most circRNAs involved in esophageal squamous cell carcinoma (ESCC) remain undefined, and the underlying molecular mechanisms mediated by circRNAs are largely unclear. Here, we screened human circRNA expression profiles in ESCC tissues and found significantly increased expression of hsa_circ_0000277 (termed circPDE3B) in ESCC tissues and cell lines compared to the normal controls. Moreover, higher circPDE3B expression in patients with ESCC was correlated with advanced tumor-node-metastasis (TNM) stage and dismal prognosis. Functional experiments demonstrated that circPDE3B promoted the tumorigenesis and metastasis of ESCC cells in vitro and in vivo. Mechanistically, bioinformatics analysis, a dual-luciferase reporter assay, and anti-AGO2 RNA immunoprecipitation showed that circPDE3B could act as a competing endogenous RNA (ceRNA) by harboring miR-4766-5p to eliminate the inhibitory effect on the target gene laminin α1 (LAMA1). In addition, LAMA1 was significantly upregulated in ESCC tissues and was positively associated with the aggressive oncogenic phenotype. More importantly, rescue experiments revealed that the oncogenic role of circPDE3B in ESCC is partly dependent on the miR-4766-5p/LAMA1 axis. Furthermore, bioinformatics analysis combined with validation experiments showed that epithelial-mesenchymal transition (EMT) activation was involved in the oncogenic functions of the circPDE3B-miR-4766-5p/LAMA1 axis in ESCC. Taken together, we demonstrate for the first time that the circPDE3B/miR-4766-5p/LAMA1 axis functions as an oncogenic factor in promoting ESCC cell proliferation, migration, and invasion by inducing EMT, implying its potential prognostic and therapeutic significance in ESCC.

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.

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.