A modified model for predicting mortality after transjugular intrahepatic portosystemic shunt: A multicentre study.

BACKGROUND AND AIMS: The transjugular intrahepatic portosystemic shunt has controversial survival benefits; thus, patient screening should be performed preoperatively. In this study, we aimed to develop a model to predict post-transjugular intrahepatic portosystemic shunt mortality to aid clinical decision making. METHODS: A total of 811 patients undergoing transjugular intrahepatic portosystemic shunt from five hospitals were divided into the training and external validation data sets. A modified prediction model of post-transjugular intrahepatic portosystemic shunt mortality (ModelMT ) was built after performing logistic regression. To verify the improved performance of ModelMT , we compared it with seven previous models, both in discrimination and calibration. Furthermore, patients were stratified into low-, medium-, high- and extremely high-risk subgroups. RESULTS: ModelMT demonstrated a satisfying predictive efficiency in both discrimination and calibration, with an area under the curve of .875 in the training set and .852 in the validation set. Compared to previous models (ALBI, BILI-PLT, MELD-Na, MOTS, FIPS, MELD, CLIF-C AD), ModelMT showed superior performance in discrimination by statistical difference in the Delong test, net reclassification improvement and integrated discrimination improvement (all p < .050). Similar results were observed in calibration. Low-, medium-, high- and extremely high-risk groups were defined by scores of ≤160, 160-180, 180-200 and >200, respectively. To facilitate future clinical application, we also built an applet for ModelMT . CONCLUSIONS: We successfully developed a predictive model with improved performance to assist in decision making for transjugular intrahepatic portosystemic shunt according to survival benefits.

Idarubicin versus epirubicin in drug-eluting beads-transarterial chemoembolization for treating hepatocellular carcinoma: A real-world retrospective study.

The purpose of this study was to compare the efficacy and safety of idarubicin-loaded drug-eluting beads-transarterial chemoembolization (IDA-TACE) and epirubicin-loaded drug-eluting beads-TACE (EPI-TACE) in treating hepatocellular carcinoma (HCC). All patients with HCC treated with TACE in our hospital between June 2020 and January 2022 were screened. The included patients were divided into the IDA-TACE group and EPI-TACE group to compare overall survival (OS), time to progression (TTP), objective response rate (ORR), and adverse events. There were 55 patients each in the IDA-TACE and EPI-TACE groups. Compared with the EPI-TACE group, the median TTP in the IDA-TACE group was not significantly different (10.50 vs. 9.23 months; HR 0.68; 95% CI 0.40-1.16; P = 0.154), whereas the survival status in the IDA-TACE group tended to be better (neither achieved; HR 0.47; 95% CI 0.22-1.02; P = 0.055). Based on the Barcelona Clinic Liver Cancer staging system for subgroup analysis, considering stage C patients, the IDA-TACE group performed significantly better in terms of ORR (77.1% vs. 54.3%, P = 0.044), median TTP (10.93 vs. 5.20 months; HR 0.46; 95% CI 0.24-0.89; P = 0.021), and median OS (not achieved vs. 17.80 months; HR 0.41; 95% CI 0.18-0.93; P = 0.033). Considering stage B patients, there were no significant differences between the IDA-TACE and EPI-TACE groups in terms of ORR (80.0% vs. 80.0%, P = 1.000), median TTP (10.20 vs. 11.2 months; HR 1.41; 95% CI 0.54-3.65; P = 0.483), or median OS (neither achieved, HR 0.47; 95% CI 0.04-5.24; P = 0.543). Notably, leukopenia was more common in the IDA-TACE group (20.0%, P = 0.052), and fever was more common in the EPI-TACE group (49.1%, P = 0.010). IDA-TACE was more effective than EPI-TACE in treating advanced-stage HCC and comparable in treating intermediate-stage HCC.

6-mm shunt transjugular intrahepatic portosystemic shunt in patients with severe liver atrophy and variceal bleeding.

OBJECTIVES: We proposed a strategy for the creation of a 6-mm transjugular intrahepatic portosystemic shunt (TIPS) and to assess its effectiveness compared to a conventional 8-mm shunt for TIPS-induced hepatic encephalopathy (HE). METHODS: Patients were reviewed retrospectively using propensity score matching (1:1) and divided into 6-mm and 8-mm shunt groups based on shunt diameter. The stent patency, HE incidence, and rebleeding rate between the two groups were then compared. RESULTS: From January 2018 to June 2021, both 6-mm shunt group and 8-mm shunt group included 58 patients. The 6-mm shunt group had significantly smaller liver volumes (879.3 ± 237.1 vs. 1008.8 ± 293.0; p = 0.010), and the median stent patency times were 30.7 and 33.8 months in the 6-mm and 8-mm groups, respectively (p = 0.124). No statistically significant difference was found between the two groups in the 1-year (8.6% vs. 3.4%; p = 0.242) and 2-year (17.2% vs. 12.1%; p = 0.242) rebleeding rates. The 1-year cumulative incidences of overt HE were 12.1% and 27.6% in the 6-mm and 8-mm groups, respectively (p = 0.040), and the 2-year cumulative overt HE incidences in these groups were 19.0% and 36.2%, respectively (p = 0.038). Notably, patients with a 6-mm shunt also experienced less hepatic impairment. CONCLUSIONS: For patients with variceal bleeding and a small liver volume, the 6-mm shunt significantly reduced the incidence of overt HE, protected perioperative liver function, and did not affect stent patency or rebleeding rate. CLINICAL RELEVANCE STATEMENT: For patients with variceal bleeding with small liver volume, the 6-mm transjugular intrahepatic portosystemic shunt (TIPS) significantly reduced the incidence of overt hepatic encephalopathy after TIPS, protected perioperative liver function, and did not affect stent patency and rebleeding rate. KEY POINTS: • A strategy for the creation of a 6-mm transjugular intrahepatic portosystemic shunt for patients with variceal bleeding and a small liver volume was proposed. • The 6-mm transjugular intrahepatic portosystemic shunt significantly reduced the incidence of overt hepatic encephalopathy. • The 6-mm transjugular intrahepatic portosystemic shunt did not affect stent patency or rebleeding rate.

Long-term Outcomes of Patients with Hepatocellular Carcinoma Who Underwent Microwave Ablation after Downstaging with Transarterial Chemoembolization to Barcelona Clinic Liver Cancer Stage A.

PURPOSE: To compare the clinical results of microwave ablation (MWA) between patients downstaged to Barcelona Clinic Liver Cancer (BCLC) Stage A with transarterial chemoembolization (TACE) and those initially classified as BCLC Stage A. MATERIALS AND METHODS: From January 2012 to May 2017, 1,087 patients were reviewed retrospectively using propensity score matching (1:1): 86 patients underwent MWA as a curative treatment after downstaging to BCLC Stage A by TACE (downstaging group) and 86 patients initially classified as BCLC Stage A underwent MWA (control group). The overall survival (OS) and disease-free survival (DFS) between the 2 groups were compared. RESULTS: The 1-, 3-, and 5-year OS rates were 95.3%, 79.1%, and 58.1%, respectively, in the downstaging group and 93.0%, 81.4%, and 61.6%, respectively, in the control group (hazard ratio [HR], 0.75; 95% CI, 0.50-1.13; P = .162). The 1-, 3-, and 5-year DFS rates were 80.2%, 50.0%, and 24.4%, respectively, in the downstaging group and 77.9%, 52.3%, and 27.9%, respectively, in the control group (HR, 1.08; 95% CI, 0.76-1.53; P = .678). No significant differences were found in OS and DFS. CONCLUSIONS: The long-term prognosis in patients with HCC who underwent MWA after downstaging to BCLC Stage A using TACE was similar to that in patients with initial BCLC Stage A.

DNA N6-methyladenine involvement and regulation of hepatocellular carcinoma development.

DNA N6-methyladenine (6 mA) is a new type of DNA methylation identified in various eukaryotic cells. However, its alteration and genomic distribution features in hepatocellular carcinoma (HCC) remain elusive. In this study, we found that N6AMT1 overexpression increased HCC cell viability, suppressed apoptosis, and enhanced migration and invasion, whereas ALKBH1 overexpression induced the opposite effects. Further, 23,779 gain-of-6 mA regions and 11,240 loss-of-6 mA regions were differentially identified in HCC tissues. The differential gain and loss of 6 mA regions were considerably enriched in intergenic regions. Moreover, 7% of the differential 6 mA modifications were associated with tumors, with 60 associated with oncogenes and 57 with tumor suppressor genes (TSGs), and 17 were common to oncogenes and TSGs. The candidate genes affected by 6 mA were filtered by gene ontology (GO) and RNA-seq. Using quantitative polymerase chain reaction (qPCR), BCL2 and PARTICL were found to be correlated with DNA 6 mA in certain HCC processes.

DEM-TACE as the initial treatment could improve the clinical efficacy of the hepatocellular carcinoma with portal vein tumor thrombus: a retrospective controlled study.

BACKGROUND: Conventional-transarterial chemoembolization (C-TACE) was proven to improve overall survival (OS) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT), drug-eluting microsphere-TACE (DEM-TACE) was supposed to provide more benefit than C-TACE in this respect. PURPOSE: To compare the safety and efficacy between DEM-TACE and C-TACE as the initial treatment in HCC patients with PVTT and to identify prognostic factors of OS. METHODS: The medical records of advanced HCC patients with PVTT who underwent DEM-TACE or C-TACE as the initial thearpy from September 2015 with mean follow-up time 14.9 ± 1.2 (95% CI 12.6-17.2) months were retrospectively evaluated. A total of 97 patients were included, 49 patients in the DEM-TACE group and 48 in the C-TACE group. Adverse events (AEs) related to TACE were compared. Tumor and PVTT radiologic response, time to tumor progression (TTP) and OS were calculated and compared in both groups. RESULTS: Patients in DEM-TACE group had a better radiologic response (Tumr response: 89.8% vs. 75.0%; PVTT response: 85.7% vs. 70.8%; overall response: 79.6% vs. 58.3%, P = 0.024) and longer TTP (7.0 months vs. 4.0 months, P = 0.040) than patients in C-TACE group. A lower incidence of abdominal pain was found in the DEM-TACE group than in C-TACE group (21 vs. 31, P = 0.032), but there were no significant differences between DEM-TACE and C-TACE patients in any other AEs reported. When compared to C-TACE, DEM-TACE also showed significant OS benefits (12.0 months vs. 9.0 months, P = 0.027). DEM-TACE treatment, the absence of arterioportal shunt (APS), lower AFP value and better PVTT radiologic response were the independent prognostic factors for OS in univariate/multivariate analyses, which provided us with a guide for better patient selection. CONCLUSIONS: Based on our retrospective study, DEM-TACE can be performed safely and might be superior to C-TACE as the initial treatment for HCC patients with PVTT. TRIAL REGISTRATION: Retrospectively registered.

Identification of circRNAs involved in the development of hepatocellular carcinoma after insufficient radiofrequency ablation.

Previous studies have reported that circular RNAs (circRNAs) play a key role in the pathogenesis and progression of various diseases. In the present study, we aimed to identify potential circRNAs associated with the progression of hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (IRFA). A xenograft mouse IRFA model was initially established, and immunohistochemical staining (IHC) and polymerase chain reaction (PCR) were performed to confirm the expression of programmed cell death-ligand 1 (PD-L1) and vascular endothelial growth factor receptor-1 (VEGFR-1). CircRNA expression alterations were screened by next-generation sequencing (RNA-seq). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to predict the function of genes coding differentially expressed circRNAs. The selected circRNAs were validated utilizing PCR and Sanger sequencing. The relationships between circRNAs, microRNAs, PD-L1, and VEGFR-1 were predicted by bioinformatics. Overall, a total of 612 circRNAs were differentially expressed in IRFA-treated subcutaneous tumorigenesis tissue. Among them, 435 circRNAs were significantly upregulated and 177 circRNAs were downregulated. GO and KEGG analyses were employed to predict the functions of these circRNAs. Thereafter, quantitative reverse transcription PCR (qRT-PCR) assays determined that these seven circRNAs were overexpressed in the IRFA group, which was consistent with the RNA-seq results. Based on the bioinformatic analysis, seven circRNAs confirmed by Sanger sequencing were predicted to likely regulate PD-L1 and VEGFR-1 expression levels by functioning as sponges for microRNAs (miRNAs) and forming a circRNA-miRNA-PD-L1/VEGFR-1 regulatory network. Finally, IHC and qRT-PCR of PD-L1 and VEGFR-1 confirmed the activation of this pathway. Taken together, we report that differentially expressed circRNAs might simultaneously regulate PD-L1 and VEGFR-1 in the IRFA tissues, which provides a novel view of circRNAs in HCC progression after the IRFA procedure.

DDX24 Mutations Associated With Malformations of Major Vessels to the Viscera.

Vascular malformations present diagnostic and treatment challenges. In particular, malformations of vessels to the viscera are often diagnosed late or incorrectly due to the insidious onset and deep location of the disease. Therefore, a better knowledge of the genetic mutations underlying such diseases is needed. Here, we evaluated a four-generation family carrying vascular malformations of major vessels that affect multiple organs, which we named "multiorgan venous and lymphatic defect" (MOVLD) syndrome. Genetic analyses identified an association between a mutation in DEAD-box helicase 24 (DDX24), a gene for which the function is largely unknown, and MOVLD. Next, we screened 161 patients with sporadic vascular malformations of similar phenotype to our MOVLD family and found the same mutation or one of the two additional DDX24 mutations in 26 cases. Structural modeling revealed that two of the mutations are located within the adenosine triphosphate-binding domain of DDX24. Knockdown of DDX24 expression in endothelial cells resulted in elevated migration and tube formation. Transcriptomic analysis linked DDX24 to vascular system-related functions. Conclusion: Our results provide a link between DDX24 and vascular malformation and indicate a crucial role for DDX24 in endothelial cell functions; these findings create an opportunity for genetic diagnosis and therapeutic targeting of malformations of vessels to the viscera.

Percutaneous transhepatic intrahepatic portosystemic shunt for variceal bleeding with chronic portal vein occlusion after splenectomy.

OBJECTIVES: The purpose of this study was to introduce a modified transjugular intrahepatic portosystemic shunt (TIPS), a percutaneous transhepatic intrahepatic portosystemic shunt (PTIPS), and to evaluate its feasibility and efficacy in patients with variceal bleeding with chronic portal vein occlusion (CPVO) after splenectomy. METHODS: Twenty-four cirrhotic patients with CPVO after splenectomy who received PTIPS between 2010 and 2015 were included in this retrospective study. The indication was elective control of variceal bleeding. Success rates, effectiveness and complications were evaluated, with comparison of the pre- and post-portosystemic pressure gradient (PPG). Patients' clinical outcomes and shunt patency were followed periodically. RESULTS: PTIPS was successfully placed in 22 patients (91.7%) and failed in two. The mean PPG fell from 22.0 ± 4.9 mmHg to 10.6 ± 1.6 mmHg after successful PTIPS (p < 0.05). No fatal procedural complications occurred. During the median follow-up of 29 months, shunt dysfunction occurred in five cases and hepatic encephalopathy in four cases. Three patients died because of rebleeding, hepatic failure and pulmonary disease, respectively. The other patients remained asymptomatic and the shunts patent. CONCLUSIONS: We conclude that PTIPS, as a modified TIPS procedure with a high success rate, is safe and effective for variceal bleeding with CPVO after splenectomy. KEY POINTS: • Portal vein occlusion used to be contraindication to transjugular intrahepatic portosystemic shunt. • Portal vein thrombosis is common in patients with previous splenectomy. • We developed a new method, percutaneous transhepatic intrahepatic portosystemic shunt (PTIPS). • PTIPS is feasible in patients with portal vein thrombosis and splenectomy. • PTIPS is effective and safe for these kind of complicated portal hypertension.

Amelioration of cirrhotic portal hypertension by targeted cyclooxygenase-1 siRNA delivery to liver sinusoidal endothelium with polyethylenimine grafted hyaluronic acid.

Portal hypertension (PH), a leading cause of mortality in cirrhosis, lacks effective clinical therapeutic strategies. The increased thromboxane A2 (TXA2), derived primarily from the upregulation of cyclooxygenase-1 (COX-1) in cirrhotic liver sinusoidal endothelial cells (LSECs), is responsible for hepatic endothelial dysfunction and PH. Thus, blocking the COX-1 pathway in cirrhotic LSECs may benefit the treatment of PH. In this study, hyaluronate-graft-polyethylenimine (HA-PEI) was synthesized for the targeted delivery of COX-1 siRNA to LSECs. Compared to non-targeted PEI, HA-PEI mediated much more efficient siRNA delivery, which resulted in potent targeted gene silencing in LSECs. In vivo, HA-PEI notably increased the accumulation of siRNA along the sinusoidal lining of the liver, inhibited over-activation of the COX-1/TXA2 pathway in LSECs, and successfully reduced portal pressure in cirrhotic mice. These results highlight the potential of HA-PEI complexed siRNA to serve as a LSECs-specific nanomedical system for effective gene therapy in PH.

Alanine aminotransferase to hemoglobin ratio is an indicator for disease progression for hepatocellular carcinoma patients receiving transcatheter arterial chemoembolization.

The prognosis of hepatocellular carcinoma (HCC) patients receiving transcatheter arterial chemoembolization (TACE) is far from being identified. The present study aimed to assess the role of blood cell counts, routine liver function tests, and alanine aminotransferase to hemoglobin ratio (AHR) in predicting the progression-free survival (PFS) of these patients. A total of 243 HCC patients receiving TACE were analyzed retrospectively. Cancer of the Liver Italian Program (CLIP) score system was indentified to be the best score system for this patient subgroup according to the Akaike information criterion (AIC) index and linear trend χ (2). Then, prognostic value of parameters was determined by integration into the CLIP score system. As a result, AHR was confirmed to be an independent predictor for the PFS of HCC patients receiving TACE (p = 0.001) with the other parameters failing to reach statistical significance. Moreover, AHR improved the performance of CLIP by adjusting into it, thus improving its discriminatory ability. AHR defined ≤0.4583 as low level and >0.4583 as high level. And, patients were also dichotomized into two groups accordingly. HCC patients receiving TACE with low AHR presented higher 1 year DCR (41.9 vs 18.1 %) compared with patients with high AHR levels. Furthermore, AHR level was associated with prognostic factors such as lower ALP, total bilirubin, and portal vein thrombosis. In summary, the present study firstly indentified AHR as an independent prognostic factor in HCC patients receiving TACE. The subgroup of HCC patients with lower AHR presented preferable disease control and were the idealistic candidates for TACE.

Partial splenic embolization for thrombocytopenia in liver cirrhosis: predictive factors for platelet increment and risk factors for major complications.

OBJECTIVES: To investigate the predictors of platelet increment and risk factors for major complications after partial splenic embolization (PSE) in cirrhosis. METHODS: Between March 2010 and June 2012, 52 cirrhotic patients with severe thrombocytopenia underwent PSE. Multiple variables were analyzed to identify the correlated factors affecting platelet increment and major complications after PSE. RESULTS: Linear mixed model analysis indicated the splenic infarction ratio (P < 0.001), non-infarcted splenic volume (P = 0.012), and cholinesterase level (P < 0.001) were significantly associated with the platelet increment after PSE. In receiver operating characteristic (ROC) analysis, the cut-off values of the splenic infarction ratio, and non-infarcted splenic volume for achieving an increment of ≥60.0 × 10(9)/L in platelet counts at 1 year after PSE were 64.3% and 245.8 mL, respectively. After PSE, eight patients developed major complications. Multivariate logistic regression analysis indicated major complications were significantly associated with the infarcted splenic volume (P = 0.024) and Child-Pugh score (P = 0.018). In ROC analysis, the cut-off values of these two factors for discriminating the uncomplicated and complicated were 513.1 mL and 9.5, respectively. CONCLUSIONS: The platelet increment after PSE depends on the splenic infarction ratio, non-infarcted splenic volume and cholinesterase level. But a large infarcted splenic volume and a high Child-Pugh score may cause complications. KEY POINTS: • The platelet increment after PSE greatly depends on the splenic infarction ratio. • The non-infarcted splenic volume significantly affects the efficacy of PSE. • A high cholinesterase level contributes to the improvement of thrombocytopenia after PSE. • The non-infarcted splenic volume significantly affects the relapse of hypersplenism. • Complications are significantly associated with the infarcted splenic volume and Child-Pugh score.

Survival benefit of chemoembolization plus Iodine125 seed implantation in unresectable hepatitis B-related hepatocellular carcinoma with PVTT: a retrospective matched cohort study.

OBJECTIVES: To investigate the survival benefit of transarterial chemoembolization (TACE) plus Iodine125 seed implantation (TACE-Iodine125) in hepatitis B-related HCC patients with portal vein tumour thrombus (PVTT) and the underlying prognostic factors. METHODS: A retrospective matched cohort study was performed on consecutive HCC patients with PVTT from January 2011 to June 2014. Seventy patients (TACE-Iodine125 group) who underwent TACE-Iodine125 were compared with a historical case-matched control group of 140 patients (TACE group) who received TACE alone. The survival of patients and the underlying prognostic factors were analysed. RESULTS: The median survival times of the TACE-Iodine125 and TACE groups were 11.0 and 7.5 months, respectively (p < 0.001). The survival probability at 12, 24, and 36 months was 50 %, 14.5 %, and 14.5 % vs. 25 %, 9 %, and 5 % in the TACE-Iodine125 and TACE groups, respectively (p < 0.001). The PVTT responders had better survival than the PVTT non-responders (p < 0.001). For the PVTT non-responders, there were no differences in the survival curves between the groups (p = 0.353). Multivariate analysis showed that type III PVTT (p < 0.001) and APS (p < 0.001) were independent predictors of poor prognosis. In contrast, the treatment modality of TACE-Iodine125 (p < 0.001) and PVTT response (p = 0.001) were favourable prognostic features. CONCLUSIONS: TACE combined with Iodine125 seed implantation may be a good choice for selected HB-HCC patients with PVTT. KEY POINTS: • TACE-Iodine125 was more effective than TACE for patients with HCC-PVTT. • The TACE-Iodine125 procedure was safe. • TACE-Iodine125 was conditional for patients with HCC-PVTT. • TACE-Iodine125 resulted in a better PVTT response compared to TACE alone. • A good PVTT response is a favourable prognostic factor.

Contrast-Enhanced Sonography for Diagnosing Collateral Transformation of the Hepatic Artery After Liver Transplantation.

OBJECTIVES: To determine the contrast-enhanced sonographic features of hepatic artery collateral transformation in patients with hepatic artery complications after liver transplantation. METHODS: Ninety-nine liver transplant recipients who underwent contrast-enhanced sonography were recruited from April 2004 to May 2014. The reference standards were conventional angiography and computed tomographic angiography. The contrast-enhanced sonographic features of the hepatic artery in patients with and without collateral arteries were retrospectively analyzed. RESULTS: All 15 patients with hepatic artery collateral transformation had hepatic artery thrombosis (10 of 15) or hepatic artery stenosis (5 of 15). The collateral artery detection rate on contrast-enhanced sonography was 100%. The peripheral hepatic artery could not be visualized by contrast-enhanced sonography in most of the patients with hepatic artery collateral transformation (14 of 15). Additionally, many small tortuous collateral arteries in the porta hepatis region were visualized during the arterial and early portal phases, showing reticulated/patchy (15 of 15) and striped (3 of 15) enhancement patterns on contrast-enhanced sonography. CONCLUSIONS: Collateral transformation of the hepatic artery in patients with hepatic artery complications after liver transplantation appears to have characteristic features on contrast-enhanced sonography, especially a reticulated or patchy enhancement pattern in the porta hepatis region during the arterial and early portal phases combined with the absence of the peripheral hepatic artery. Contrast-enhanced sonography may be a novel method for diagnosing hepatic artery collateral transformation, which may be a highly specific sign of hepatic artery thrombosis or stenosis.

[Multifunctional nano-vector for gene delivery into human adipose derived mesenchymal stem cells and in vitro cellular magnetic resonance imaging].

OBJECTIVE: To examine the feasibility and efficacy of using superparamagnetic iron oxide nanoparticles coated with polyethylene glycol-grafted polyethylenimine (PEG-g-PEI-SPION) as a carrier for gene delivery into human adipose derived mesenchymal stem cells (hADMSCs) and in vitro cellular magnetic resonance imaging (MRI). METHODS: PEG-g-PEI-SPION was synthesized as previously reported. Gel electrophoresis was performed to assess the pDNA condensation capacity of PEG-g-PEI-SPION. The particle size and zeta potential of PEG-g-PEI-SPION/pDNA complexes were determined by dynamic light scattering. Cytotoxicity of PEG-g-PEI-SPION was evaluated by CCK-8 assay with hADMSCs. Gene transfection efficiency of PEG-g-PEI-SPION in hADMSCs was quantified by flow cytometry. The cellular internalization of PEG-g-PEI-SPION/pDNA nanocomplexes was studied by confocal laser scanning microscopy and Prussian blue staining. MRI function of PEG-g-PEI-SPION was studied by in vitro cellular MRI scanning. RESULTS: PEG-g-PEI-SPION condensed pDNA to form stable complexes of 80-100 nm in diameter and showed low cytotoxicity in hADMSCs. At the optimal N/P ratio of 20, PEG-g-PEI-SPION/pDNA obtained the highest transfection efficiency of 22.8% ± 3.6% in hADMSCs. And it was higher than that obtained with lipofectamine 11.2% ± 2.6% (P < 0.05). Furthermore, hADMSCs labeled with PEG-g-PEI-SPION showed sensitive low signal intensity on MRI T2-weighted images in vitro. CONCLUSION: PEG-g-PEI-SPION is an efficient and MRI-visible nano-vector for gene delivery into hADMSCs.

[Application of hepatocellular carcinoma targeted multifunctional nanocarriers].

OBJECTIVE: To synthesize the RGD-modified magnetic resonance imaging (MRI)-visible gene transfer nanocarrier and assess its gene delivery ability and MRI visibility for hepatocellular carcinoma. METHODS: The multifunctional nanocarrier RGD-PEG-PEI-SPION was constructed. And the degree of binding between nanocarrier and siRNA was determined by agarose gel electrophoresis. The zeta potential and particle size of cationic polymer vectors were measured with a Zeta-Plus instrument. Immunocytochemical assay was performed for detecting the expression of α(v)ß(3) in Bel-7402 cells. The active targeting ability of nanocarrier to Bel-7402 cells was evaluated by flow cytometry and laser confocal microcopy. The MRI visibility of nanocarrier to Bel-7402 cells was assessed. RESULTS: RGD-PEG-PEI-SPION could condense siRNA entirely at a N/P ratio of 2.8; the membranes of Bel-7402 cells possessed an enrichment of α(v)ß(3) receptors. At a nitrogen/phosphate ratio of 10, the particle size of RGD-PEG-PEI-SPION/siRNA attained a constant size of 85.2 ± 5.6 nm, the zeta potential reached +12.4 ± 1.2 mV, the gene transfection efficiency of nanocarrier to Bel-7402 cells attained 71.2% ± 2.1% and the cells showed significantly stronger RGD-PEG-PEI-SPION (red) and siRNA (green) fluorescence under laser confocal microcopy. The cells incubated with RGD-PEG-PEI-SPION exhibited significantly lower normalized MR T(2)(*)WI signal intensity. CONCLUSION: A RGD-modified MRI-visible gene delivery nanocarrier RGD-PEG-PEI-SPION has been successfully synthesized.It has a higher transfection efficiency of transferring siRNA into Bel-7402 cells and could sensitively detect hepatocellular carcinoma with MRI.

Causal effects of immune cells in glioblastoma: a Bayesian Mendelian Randomization study.

Background: Glioblastoma (GBM) is a highly malignant brain tumor, and immune cells play a crucial role in its initiation and progression. The immune system's cellular components, including various types of lymphocytes, macrophages, and dendritic cells, among others, engage in intricate interactions with GBM. However, the precise nature of these interactions remains to be conclusively determined. Method: In this study, a comprehensive two-sample Mendelian Randomization (MR) analysis was conducted to elucidate the causal relationship between immune cell features and the incidence of GBM. Utilizing publicly available genetic data, we investigated the causal associations between 731 immune cell signatures and the risk of GBM. Subsequently, we conducted a reverse Mendelian randomization analysis to rule out reverse causation. Finally, it was concluded that there is a unidirectional causal relationship between three subtypes of immune cells and GBM. Comprehensive sensitivity analyses were employed to validate the results robustness, heterogeneity, and presence of horizontal pleiotropy. To enhance the accuracy of our results, we concurrently subjected them to Bayesian analysis. Results: After conducting MR analyses, we identified 10 immune phenotypes that counteract glioblastoma, with the most protective being FSC-A on Natural Killer T cells (OR = 0.688, CI = 0.515-0.918, P = 0.011). Additionally, we found 11 immune cell subtypes that promote GBM incidence, including CD62L- HLA DR++ monocyte % monocyte (OR = 1.522, CI = 1.004-2.307, P = 0.048), CD4+CD8+ T cell % leukocyte (OR = 1.387, CI = 1.031-1.866, P = 0.031). Following the implementation of reverse MR analysis, where glioblastoma served as the exposure variable and the outcomes included 21 target immune cell subtypes, we discerned that only three cell subtypes (CD45 on CD33+ HLA DR+ CD14dim, CD33+ HLA DR+ Absolute Count, and IgD+ CD24+ B cell Absolute Count) exhibited a unidirectional causal association with glioblastoma. Conclusion: Our study has genetically demonstrated the close relationship between immune cells and GBM, guiding future clinical research.

Transjugular intrahepatic portosystemic shunt for portal hypertension with chronic portal vein occlusion.

PURPOSE: This study aims to evaluate the long-term patency of transjugular intrahepatic portosystemic shunt (TIPS) and determine the predictors of shunt dysfunction in patients with chronic portal vein occlusion (CPVO). METHOD: This retrospective study was conducted from December 2010 to December 2020 in patients with portal hypertension and CPVO. Patients were followed up from initial TIPS insertion to December 2022 or death. Details of TIPS procedure, adverse events and clinical outcomes were recorded. The cumulative rate of shunt patency was calculated by the Kaplan-Meier method and compared by using the log-rank test. Independent predictors of shunt dysfunction were calculated with the Cox regression model. A nomogram comprising independent variables was developed to enhance the predictive accuracy of shunt patency. RESULTS: One hundred six patients (mean age, 45.3 years ± 13.6; 71 males and 35 females) were enrolled in the study. TIPS procedure was technically successful in 100 of 106 patients (94.3 %). The primary shunt patency rates for all 100 patients were 78.9 %, 74.7 %, 67.2 %, and 62.4 % at 6, 12, 24, and 36 months, respectively, and the overall shunt patency rates were 88.9 %, 86.8 %, 83.6 %, and 81.2 % at 6, 12, 24, and 36 months, respectively. Independent predictor of shunt dysfunction were inadequate inflow from superior mesenteric vein or splenic vein (the maximum diameter < 8 mm) and platelet count ≥ 300 × 109/L. The developed nomogram is a simple tool for accurately predicting shunt patency. CONCLUSIONS: In patients with CPVO, inadequate inflow and high platelet count are important factors for TIPS dysfunction.