Tirapazamine (TPZ) is a bioreductive agent with selective antitumor activity under hypoxic conditions; however, its systemic toxicity and delivery efficiency limit its clinical application. This study aimed to develop a TPZ delivery system based on nanobubbles (NBs), combining ultrasound-targeted microbubble destruction (UTMD) and transcatheter arterial chemoembolization (TACE) for treating hepatocellular carcinoma (HCC) to enhance therapeutic efficacy and reduce adverse effects. TPZ-NBs were fabricated using a high-shear dispersion method and characterized for their physicochemical properties, encapsulation efficiency, and drug release profiles. In vitro studies evaluated the effects of TPZ-NBs on hepatoma cell proliferation and migration under hypoxic conditions. Using a rabbit VX2 liver cancer model, we compared the control group, TACE group, TPZ-NBs + TACE group, and TPZ-NBs + UTMD + TACE group in terms of tumor necrosis, drug delivery efficiency, and safety profiles. TPZ-NBs demonstrated favorable encapsulation efficiency (35.81

Background:Budd-Chiari syndrome (BCS) presents diagnostic and treatment challenges owing to its insidious onset. Genetic variants associated with BCS vary geographically; in Asian populations, the condition is primarily caused by membranous obstruction composed of endothelial cells (ECs). A better understanding of the genetic pathogenesis of membranous BCS may offer new insights into disease mechanisms. Methods:This study employed whole-exome sequencing to identify candidate genes responsible for EC abnormalities in 485 patients with membranous BCS and 329 patients with vascular malformations (VaMs). Functional investigations were conducted to validate the selected genes in vitro and in vivo. Results:Whole-exome data revealed that the frequency of variants in the vascular function-related KLHDC2 exceeded that of JAK2 in BCS. Knockdown of KLHDC2 promoted adhesion and suppressed proliferation of ECs. In addition, 92 genes enriched for rare variants overlapped between BCS and VaMs. Systems biology analysis revealed two gene clusters, including COMMD9, enriched in proteins intolerant to loss-of-function mutations. Furthermore, suppression of COMMD9 impaired EC migration and tube formation, inhibited subintestinal angiogenic sprouting in zebrafish, and elevated EC adhesion. Transcriptomic analysis linked COMMD9 to EC abnormalities via the PI3K-Akt pathway. Commd9 knockdown promoted venous hypercoagulability in vivo following drug or ligation-induced stenosis. Conclusions:These findings indicate that multiple rare genetic variants, particularly in COMMD9, are involved in the development of membranous BCS by regulating hypercoagulability induced by EC abnormalities. These findings may help guide future clinical research towards improved understanding and treatment of BCS.

BackgroundThis study aims to investigate the durability and outcomes of endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAAs) using the low-profile INCRAFT Stent-Graft System.MethodsBaseline characteristics, procedural data, and clinical outcomes were retrospectively collected from patients diagnosed with infrarenal AAAs, who underwent elective EVAR using the INCRAFT device from August 2017 to March 2023 at our institute.ResultsThirty-two patients with a mean age of 72.72 ± 7.18 years were included in the study, and 84.4% of the patients had hostile iliac accesses. The immediate technical success rate of INCRAFT device implantation was 100%, and clinical success was obtained in all patients post-procedure. The intraprocedural endoleak (EL) rate was 15.6%, with three cases of type 1a EL and two cases of type 1b EL (resolved after percutaneous transluminal angioplasty). Reintervention was required in 5 patients, four of whom underwent successful transarterial embolisation for type 2 EL; one of the patient underwent proximal extension for type 1a EL. During a median post-procedural follow-up of 32 months, there were no aneurysm-related deaths, stent-graft migration, or aneurysm-related ruptures. Freedom from all-cause mortality was 93.8%, and freedom from secondary intervention was 84.4% at 3 years.ConclusionsIn this real-world study setting, the midterm outcomes of the INCRAFT Stent-Graft System showed no aneurysm-related deaths. The use of this low-profile device for infrarenal AAAs is associated with sustained success and relatively low rates of reintervention during follow-up, which represents a safe and effective option for endovascular treatment in patients with hostile iliac accesses.

Background:Atherosclerosis is a long-term inflammatory disorder of the arterial wall, characterized by lipid deposition and infiltration of immune cells. Recent studies suggest that cuproptosis may participate in the progression of atherosclerosis. Methods:Multiple scRNA-seq and bulk RNA-seq datasets were integrated to systematically characterize cuproptosis patterns in atherosclerosis. Differential expression analysis based on cuproptosis scores identified cuproptosis-modulating genes, which were further refined using least absolute shrinkage and selection operator, decision tree, and XGBoost algorithms. CellChat analysis explored the effect of ARID1B expression on intercellular communication, while immune infiltration patterns were assessed via single-sample gene set enrichment analysis. ApoE-/- mice served as the in vivo model of atherosclerosis to confirmed relationships among cuproptosis, ARID1B expression, and immune infiltration in plaques. Results:Cuproptosis activity was significantly elevated in atherosclerotic tissues compared with normal arteries, with macrophages exhibiting the highest cuproptosis scores. Distinct expression profiles of cuproptosis-related genes, together with divergent immune infiltration landscapes, were observed between the high and low cuproptosis score atherosclerosis groups. ARID1B was identified as a gene discriminating cuproptosis status in atherosclerosis pathology, with significantly reduced expression in the disease group. Functional enrichment analyses suggested that ARID1B-associated networks were mainly involved in immune cell adhesion, activation, and differentiation. In vivo validation further confirmed that ARID1B expression was significantly reduced in the atherosclerosis group, which was associated with prominent T cell and macrophage infiltration. Conclusion:Cuproptosis-related gene ARID1B may reshape immune infiltration patterns in atherosclerosis, positioning it as a promising therapeutic target.

Intraluminal drug coated devices, such as paclitaxel (PTX)-coated balloons, are commonly used to treat arterial occlusive diseases caused by atherosclerosis. However, their efficacy is limited by drug loss, poor drug retention, insufficient penetration and high costs. Nanoparticles with molecular targeting capabilities offer a promising solution to these challenges. Collagen hybridizing peptide (CHP) specifically binds to degraded collagen in atherosclerotic plaques, enabling precise molecular imaging and targeted therapy. In this study, we demonstrated that collagen degradation was significantly elevated in atherosclerotic plaques and could be effectively identified by CHP in both atherosclerosis patients and mice models. Using the emerging copper-free click chemistry reaction, we functionalized the widely used albumin-based indocyanine green nanoparticles and albumin-bound paclitaxel nanoparticles with CHP, developing a targeted nanoplatform for molecular imaging and therapy. In vivo photoacoustic (PA) imaging and ex vivo fluorescence (FL) imaging revealed significantly enhanced PA and FL signals in carotid artery and aorta plaques with CHP functionalized nanoparticles engaging. Furthermore, therapeutic evaluations showed that CHP significantly improved the plaque-targeting capability of albumin-bound paclitaxel nanoparticles, thereby enhancing their therapeutic efficacy against atherosclerotic plaques. These findings highlighted CHP-functionalized albumin nanoparticles as a promising strategy for precise and effective atherosclerosis molecular imaging and treatment. 1 - Collagen hybrid peptide (CHP) specifically binds to degraded collagen in atherosclerotic plaques. 2 - Copper-free click chemistry reaction achieves efficient CHP conjugation to albumin nanoparticles. 3 - CHP functionalized albumin-based indocyanine green nanoparticles precisely target degraded collagen in atherosclerosis mice model, enabling accurate in vivo photoacoustic imaging of plaques. 4 - CHP markedly enhance targeted delivery and topical paclitaxel concentration of clinically used albumin-bounded paclitaxel in atherosclerotic plaques. 5 - CHP functionalized albumin-bounded paclitaxel nanoparticles significantly improved therapeutic efficacy of atherosclerosis without notable toxicity.

Vascular development is a precisely controlled process, yet how it is spatiotemporally orchestrated remains enigmatic. We previously identified DEAD-box RNA helicase 24 (DDX24) as a pathogenic gene for multiorgan vascular anomalies. Here, we show that DDX24 is expressed in the endothelium during embryonic angiogenesis in zebrafish. DDX24 deficiency causes intersegmental vessel hyperbranching in the trunk, but inhibits central artery angiogenesis in the brain. Mechanistically, DDX24 deficiency enhances VEGFR2 expression by direct binding to its mRNA in nonbrain endothelial cells (ECs), while suppressing GPR124/RECK-mediated Wnt signaling in brain ECs. Additionally, spatial transcriptome analysis profiles DDX24-mediated crosstalk between ECs and neighboring cells. Finally, pharmacological targeting of these two pathways in a temporal manner can rescue the phenotypes induced by DDX24 deficiency. Overall, our findings highlight an essential role for DDX24 in the spatiotemporal regulation of developmental angiogenesis.

Atherosclerosis is a chronic inflammatory disease affecting arterial walls and remains a leading cause of morbidity and mortality worldwide. While anti-inflammatory therapy is widely recognized as a critical component in the management of atherosclerosis, current treatments are often limited by adverse effects and suboptimal efficacy. Membrane-derived nanovesicles have demonstrated excellent biocompatibility and prolonged circulation times, making them effective drug delivery carriers. However, their targeting capabilities remain limited, as only a small fraction of transmembrane proteins possesses intrinsic targeting functions. To overcome these limitations and leverage the targeting capability of folate in inflammatory disease, we designed biomimetic nanovesicles modified with folate by covalently conjugating folate-C6-PEG4-NHS to nanovesicles under physiological conditions enabling efficient drug delivery to atherosclerotic plaques. Meanwhile we also identified the PU.1 inhibitor DB1976 as an anti-inflammatory target for the treatment of atherosclerosis. Mechanistically, DB1976 suppresses inflammation by inhibiting the IL-1β/NF-κB signaling pathway, reducing reactive oxygen species (ROS) levels, and decreasing apoptosis rates. Folate-modified biomimetic nanovesicles loaded with DB1976 achieved promising therapeutic outcomes. In summary, folate-modified macrophage biomimetic nanovesicles loaded with a PU.1 inhibitor effectively alleviate atherosclerosis by targeting inflammation in atherosclerotic plaques, highlighting their potential as a promising therapeutic strategy for atherosclerosis treatment.

PURPOSE:To describe portal vein cannulation under adjunct guidance for transjugular intrahepatic portosystemic shunts (TIPS). METHODS:Medical records of 86 patients who underwent TIPS, including conventional TIPS, 3D volumetric CT image fusion (CT-fluoroscopy image fusion)-guided TIPS, and trans-abdominal ultrasound (US)-guided TIPS at our institute from March 2016 to June 2024 were reviewed. Baseline characteristics, clinical outcomes, and procedural data were analyzed. RESULTS:Technical success was achieved in 35 conventional TIPS patients (92.11 %), 20 CT-fluoroscopy image fusion-guided TIPS patients (95.24 %), and 26 transabdominal US-guided TIPS patients (96.30 %). Among patients who underwent a successful procedure, the procedural time and contrast usage were lower in the CT-fluoroscopy image fusion-guided and trans-abdominal US-guided TIPS groups than in the conventional group. There was a statistical significance in the cumulative fluoroscopic time between CT-fluoroscopy image fusion-guided TIPS and conventional TIPS groups (43.19 ± 14.92 vs 63.05 ± 30.33 min, p = 0.012). No immediate experienced complications were observed. Furthermore, the incidence of post-procedural complications among the three groups was not statistically different during follow-up. CONCLUSIONS:CT-fluoroscopy image fusion and trans-abdominal US-guided portal vein cannulation are feasible, safe, and effective adjunct methods for patients undergoing TIPS. These methods provide shorter procedural time and lower contrast usage for TIPS placement.

Aims:Surveys and research on the applications of the hepatic venous pressure gradient(HVPG)are important for understanding the current status and future development of this technology in China.This article aimed to investigate the status of hepatic venous pressure gradient measurement in China in 2022. Methods:We investigated the overall status of HVPG technology in China—including hospital distribution,hospital level,annual number of cases,catheters used,average cost,indications,and current challenges by using online questionnaire.By counting the number and percentages of cases of these results,we hope to clarify the current status of HVPG measurements in China. Results:According to the survey,85 hospitals in China used HVPG technology in 2022 distributed across 29 provinces.A total of 4989 HVPG measurements were performed in all of the surveyed hospitals in 2022,of which 2813 cases(56.4％)were measured alone.The average cost of HVPG measurement was 5646.8±2327.9 CNY.Of the clinical teams who performed the measurements(sometimes multiple per hospital),94.3％(82/87)used the balloon method,and the majority of the teams(72.4％,63/87)used embolectomy catheters. Conclusions:This survey clarified the clinical application status of HVPG in China and confirmed that some medical institutions in China have established a foundation for this technology.It is still necessary to continue promoting and popularizing this technology in the future.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is associated with a loss or an imbalance of host-microorganism interactions. However, such interactions at protein levels remain largely unknown. Here, we applied a depletion-assisted metaproteomics approach to obtain in-depth host-microbiome association networks of IBD, where the core host proteins shifted from those maintaining mucosal homeostasis in controls to those involved in inflammation, proteolysis, and intestinal barrier in IBD. Microbial nodes such as short-chain fatty-acid producer-related host-microbial crosstalk were lost or suppressed by inflammatory proteins in IBD. Guided by protein-protein association networks, we employed proteomics and lipidomics to investigate the effects of UC-related core proteins S100A8, S100A9, and cytokines (IL-1β, IL-6, and TNF-α) on gut bacteria. These proteins suppressed purine nucleotide biosynthesis in stool-derived in vitro communities, which was also reduced in IBD stool samples. Single species study revealed that S100A8, S100A9, and cytokines can synergistically or antagonistically alter gut bacteria intracellular and secreted proteome, with combined S100A8 and S100A9 potently inhibiting beneficial Bifidobacterium adolescentis. Furthermore, these inflammatory proteins only altered the extracellular but not intracellular proteins of Ruminococcus gnavus. Generally, S100A8 induced more significant bacterial proteome changes than S100A9, IL-1β, IL-6, and TNF-α but gut bacteria degrade significantly more S100A8 than S100A9 in the presence of both proteins. Among the investigated species, distinct lipid alterations were only observed in Bacteroides vulgatus treated with combined S100A8, S100A9, and cytokines. These results provided a valuable resource of inflammatory protein-centric host-microbial molecular interactions.

The dysregulation of membrane protein expression has been implicated in tumorigenesis and progression, including hepatocellular carcinoma (HCC). In this study, we aimed to identify membrane proteins that modulate HCC viability. To achieve this, we performed a CRISPR activation screen targeting human genes encoding membrane-associated proteins, revealing TMX2 as a potential driver of HCC cell viability. Gain- and loss-of-function experiments demonstrated that TMX2 promoted growth and tumorigenesis of HCC. Clinically, TMX2 was an independent prognostic factor for HCC patients. It was significantly upregulated in HCC tissues and associated with poor prognosis of HCC patients. Mechanistically, TMX2 was demonstrated to promote macroautophagy/autophagy by facilitating KPNB1 nuclear export and TFEB nuclear import. In addition, TMX2 interacted with VDAC2 and VADC3, assisting in the recruitment of PRKN to defective mitochondria to promote cytoprotective mitophagy during oxidative stress. Most interestingly, HCC cells responded to oxidative stress by upregulating TMX2 expression and cell autophagy. Knockdown of TMX2 enhanced the anti-tumor effect of lenvatinib. In conclusion, our findings emphasize the pivotal role of TMX2 in driving the HCC cell viability by promoting both autophagy and mitophagy. These results suggest that TMX2 May serve as a prognostic marker and promising therapeutic target for HCC treatment.Abbreviation: CCCP: Carbonyl cyanide 3-chlorophenylhydrazone; Co-IP: co-immunoprecipitation; CRISPR: clustered regularly interspaced short palindromic repeat; ER: endoplasmic reticulum; HCC: hepatocellular carcinoma; KPNB1: karyopherin subunit beta 1; PRKN: parkin RBR E3 ubiquitin protein ligase; ROS: reactive oxygen species; TFEB: transcription factor EB; TMX2: thioredoxin related transmembrane protein 2; VDAC2: voltage dependent anion channel 2; VDAC3: voltage dependent anion channel 3; WB: western blot.

Background: Acute hepatitis is a progressive inflammatory disorder that can lead to liver failure. Endothelial permeability is the vital pathophysiological change involved in infiltrating inflammatory factors. DDX24 has been implicated in immune signaling. However, the precise role of DDX24 in immune -mediated hepatitis remains unclear. Here, we investigate the phenotype of endothelium -targeted Ddx24 conditional knockout mice with Concanavalin A (ConA)-induced hepatitis. Methods: Mice with homozygous endothelium -targeted Ddx24 conditional knockout (Ddx24flox/flox; Cdh5-Cre+) were established using the CRISPR/Cas9 mediated Cre-loxP system. We investigated the biological functions of endothelial cells derived from transgenic mice and explored the effects of Ddx24 in mice with ConA-induced hepatitis in vivo. The mass spectrometry was performed to identify the differentially expressed proteins in liver tissues of transgenic mice. Result: We successfully established mice with endothelium -targeted Ddx24 conditional knockout. The results showed migration and tube formation potentials of murine aortic endothelial cells with DDX24 silencing were significantly promoted. No differences were observed between Ddx24flox/flox; Cdh5-Cre+ and control regarding body weight and length, pathological tissue change and embryogenesis. We demonstrated Ddx24flox/flox; Cdh5Cre+ exhibited exacerbation of ConA-induced hepatitis by up -regulating TNF-alpha and IFN-gamma. Furthermore, endothelium -targeted Ddx24 conditional knockout caused vascular hyper -permeability in ConA-injected mice by down -regulating vascular integrity -associated proteins. Mechanistically, we identified Ddx24 might regulate immune -mediated hepatitis by inflammation -related permeable barrier pathways. Conclusion: These findings prove that endothelium -targeted Ddx24 conditional knockout exacerbates ConAinduced hepatitis in mice because of vascular hyper -permeability. The findings indicate a crucial role of DDX24 in regulating immune -mediated hepatitis, suggesting DDX24 as a potential therapeutic target in the disorder.

OBJECTIVE:Endovenous microwave ablation (EMA) is a recently developed thermal ablation technique used in the treatment of lower limb varicose veins. However, its efficacy and safety have been largely understudied. In the present study, we sought to explore the clinical results of EMA and radiofrequency ablation (RFA) in treating lower limb varicose veins. METHODS:Patients who underwent EMA (n = 65) or RFA (n = 46) at our institute from September 2018 to September 2020 were included in this retrospective investigation. The clinical results and complications were evaluated at 1, 3, 6, and 12 months after the procedure. The effects on disease severity and quality of life were evaluated using the venous clinical severity score and chronic venous insufficiency questionnaire (CIVIQ). RESULTS:The technical success rate was 100% for both experimental groups. Although the operative time between the two groups was comparable, the EMA technique was associated with lower direct costs (P < .001), although also with prolonged hospitalization (P < .001). We found that the use of EMA correlated with more pain at 48 hours postoperatively. Except for the visual analog scale scores, no statistically significant variations were observed in the occurrence of postoperative complications within the first 48 hours postoperatively between the EMA and RFA groups, including paresthesia, ecchymosis, induration, and phlebitis (P > .05). At 4 weeks postoperatively, significantly less pigmentation was observed in the RFA group than in the EMA group (13.04% vs 32.31%; P = .020). However, the pigmentation had resolved in all patients by 12 months postoperatively. The two groups had a reduction in the venous clinical severity scores and an increase in the CIVIQ scores after the procedure. However, the CIVIQ scores within the RFA group had increased more than had those within the EMA group (P < .05). No significant differences were found in recurrence between the two groups (EMA group, 1.54%; RFA group, 2.17%; P = .804). CONCLUSIONS:Both ablation techniques are safe and effective. RFA is associated with relatively higher treatment costs but shorter hospitalization and better quality of life improvement.

Endovascular embolization can selectively deploy embolic agents into diseased or injured blood vessels to complete the treatment. However, traditional embolic agents still face challenges, such as poor intravascular diffusivity, non‐biodegradable, unstable mechanical properties, radiolucency, and recanalization. Herein, we report a poly (lipoic acid‐tannic acid)/tromethamine/Galinstan (PLTTG) dimethyl sulfoxide (DMSO) solution‐derived hydrogel liquid embolic agent. By injecting PLTTG DMSO solution into body fluids, a PLTTG hydrogel can be formed in situ owing to the solvent exchange induced intra‐ and inter‐polymer hydrogen bonding and electrostatic interactions. Moreover, the gelation time and injection forces of the solution as well as the mechanical properties and embolic pressure of the obtained hydrogels can be adjusted by changing the concentration of PLTTG. The PLTTG hydrogel can effectively embolize the renal artery and femoral vein without recanalization and displacement in rabbit models. Furthermore, the hydrogel can embolize the ruptured femoral artery to arrest active bleeding. Owing to the advantages of the hydrogel, including adjustable gelation time, mechanical properties, viscosities, injection forces, and embolic pressure, as well as good biocompatibility and biodegradability, radiopacity, excellent embolization performance and intravascular diffusivity, easy usage, low cost, allowing it to be a potential embolic agent to treat multiple vascular diseases in clinic.

Supplementary Data from RNA Helicase DDX24 Stabilizes LAMB1 to Promote Hepatocellular Carcinoma Progression

Background: Identification of biomarkers to assist in the clinical management of hepatocellular carcinoma represents an urgent requirement. Fibulin-2 is known to contribute to the development and progression of various cancer types. This research investigated the role of fibulin-2 in hepatocellular carcinoma and explored the possible mechanisms. Methods: The expression of fibulin-2 in hepatocellular carcinoma was measured by bioinformatic analysis and confirmed by western blot and immunohistochemical staining in cell lines or patients’ samples. The clinicopathologic features of hepatocellular carcinoma patients was analyzed. Cell viability assays were used to explore the role of fibulin-2 on proliferation in hepatocellular carcinoma. Western blot was conducted to uncover changes of protein expression of Ras-MEK-ERK1/2 pathway when Fibulin-2 was overexpressed or silenced. Flow cytometry analyses were used to determine the roles of fibulin-2 in the function of apoptosis and cell cycle. Subcutaneous xenograft mouse models showed the tumor growth pattern after fibulin-2 silence in vivo. Results: We reported the upregulation of fibulin-2 in most hepatocellular carcinoma tissues and cells lines. Fibulin-2 promoted the proliferation of hepatocellular carcinoma cells in vitro by regulating Ras-MEK-ERK1/2 signaling pathway, whereas knockdown of fibulin-2 incurred the opposite effect on proliferation. Consistently, knockdown of fibulin-2 resulted in increased apoptosis and induced growth arrest during the G0/G1 phase transition. In vivo xenograft assessment confirmed that knockdown of fibulin-2 inhibited hepatocellular carcinoma tumor growth. Conclusions: Fibulin-2 exhibited tumor promotor activities in malignant progression of hepatocellular carcinoma. The results of the study highlighted the potential of fibulin-2 to be utilized as a promising biomarker and therapeutic target for hepatocellular carcinoma.

Budd-Chiari syndrome (BCS) is characterized by hepatic venous outflow obstruction, posing life-threatening risks in severe cases. Reported risk factors include inherited and acquired hypercoagulable states or other predisposing factors. However, many patients have no identifiable etiology, and causes of BCS differ between the West and East. This study recruited 500 BCS patients and 696 normal individuals for whole-exome sequencing and developed a polygenic risk scoring (PRS) model using PLINK, LASSOSUM, BLUP, and BayesA methods. Risk factors for venous thromboembolism and vascular malformations were also assessed for BCS risk prediction. Ultimately, we discovered potential BCS risk mutations, such as rs1042331, and the optimal BayesA-generated PRS model presented an AUC >0.9 in the external replication cohort. This model provides particular insights into genetic risk differences between China and the West and suggests shared genetic risks among BCS, venous thromboembolism, and vascular malformations, offering different perspectives on BCS pathogenesis.

Due to drug resistance, the clinical response to cisplatin (CDDP) from patients with liver cancer is unsatisfactory. The alleviation or overcoming of CDDP resistance is an urgent problem to be solved in clinics. Tumor cells rapidly change signal pathways to mediate drug resistance under drug exposure. Here, multiple phosphor-kinase assays were performed and c-Jun N-terminal kinase (JNK) was activated in liver cancer cells treated with CDDP. The high activity of the JNK promotes poor progression and mediates cisplatin resistance in liver cancer, leading to a poor prognosis of liver cancer. Mechanistically, the highly activated JNK phosphorylated c-Jun and ATF2 formed a heterodimer to upregulate the expression of Galectin-1, leading to promoting cisplatin resistance in liver cancer. Importantly, we simulated the clinical evolution of drug resistance in liver cancer by continuous CDDP administration in vivo. In vivo bioluminescence imaging showed the activity of JNK gradually increased during this process. Moreover, the inhibition of JNK activity by small molecular or genetic inhibitors enhanced DNA damage and overcame CDDP resistance in vitro and in vivo. Collectively, our results underline that the high activity of JNK/c-Jun-ATF2/Galectin-1 mediates cisplatin resistance in liver cancer and provides an optional scheme for dynamic monitoring of molecular activity in vivo.

Background This study aims to investigate the value of the AngioJet thrombectomy system with adjunct of catheter-directed thrombolysis (CDT) in treating lower extremity deep venous thrombosis (LEDVT). Methods 48 patients who were clinically confirmed LEDVT and treated by percutaneous mechanical thrombectomy (PMT) combined with CDT, were included in this retrospective study (AJ-CDT, n = 33; Suction-CDT, n = 15). Baseline characteristics, clinical outcomes and surveillance data were reviewed and analyzed. Results The overall clot reduction rate of AJ-CDT group was significantly higher than that of Suction-CDT group (77.86% vs 64.47%, P = .027). The CDT therapeutic time (5.75 ± 3.04 vs 7.67 ± 2.82 days, P = .045) and urokinase dosage (3.63 ± 2.16 vs 5.76 ± 2.12 million IU, P = .003) were lower in AJ-CDT group, respectively. There was statistical significance in the transient hemoglobinuria between 2 groups (72.73% vs 6.67%, P < .001). At postoperative 48 hours, the serum creatinine (Scr) value was higher in AJ-CDT group compared to Suction-CDT group statistically (78.56 ± 32.16 vs 60.21 ± 15.72 μmol/l, P = .049). However, the incidence of acute kidney injury (AKI) and uric acid (UA) concentration at postoperative 48 hours between these 2 groups were no statistical difference. There was no statistical significance in the Villalta score and post-thrombosis syndrome (PTS) incidence during postoperative follow-up. Conclusions AngioJet thrombectomy system is more effective for the treatment of LEDVT by providing a higher clot reduction rate with shorter thrombolytic time and lower thrombolytic drug dosage. However, the device-related potential risk of renal function injury should be taken appropriate precautions.