Tetraborated Intrinsically Axial Chiral Multi-resonance Thermally Activated Delayed Fluorescence Materials.

Chiral multi-resonance thermally activated delayed fluorescence (CP-MR-TADF) materials hold promise for circularly polarized organic light-emitting diodes (CP-OLEDs) and 3D displays. Herein, we present two pairs of tetraborated intrinsically axial CP-MR-TADF materials, R/S-BDBF-BOH and R/S-BDBT-BOH, with conjugation-extended bidibenzo[b,d]furan and bidibenzo[b,d]thiophene as chiral sources, which effectively participate in the distribution of the frontier molecular orbitals. Due to the heavy-atom effect, sulfur atoms are introduced to accelerate the reverse intersystem crossing process and increase the efficiency of molecules. R/S-BDBF-BOH and R/S-BDBT-BOH manifest ultra-pure blue emission with a maximum at 458/459 nm with a full width at half maximum of 27 nm, photoluminescence quantum yields of 90 %/91 %, and dissymmetry factors (|gPL|) of 6.8×10-4/8.5×10-4, respectively. Correspondingly, the CP-OLEDs exhibit good performances with an external quantum efficiency of 30.1 % and |gEL| factors of 1.2×10-3.

Regulator of G-protein signaling 14 protects the liver from ischemia-reperfusion injury by suppressing TGF-ß-activated kinase 1 activation.

BACKGROUND AND AIMS: Hepatic ischemia-reperfusion injury (IRI) is a common complication of hepatectomy and liver transplantation. However, the mechanisms underlying hepatic IRI have not been fully elucidated. Regulator of G-protein signaling 14 (RGS14) is a multifunctional scaffolding protein that integrates the G-protein and mitogen-activated protein kinase (MAPK) signaling pathways. However, the role of RGS14 in hepatic IRI remains unclear. APPROACH AND RESULTS: We found that RGS14 expression increased in mice subjected to hepatic ischemia-reperfusion (IR) surgery and during hypoxia reoxygenation in hepatocytes. We constructed global RGS14 knockout (RGS14-KO) and hepatocyte-specific RGS14 transgenic (RGS14-TG) mice to establish 70% hepatic IRI models. Histological hematoxylin and eosin staining, levels of alanine aminotransferase and aspartate aminotransferase, expression of inflammatory factors, and apoptosis were used to assess liver damage and function in these models. We found that RGS14 deficiency significantly aggravated IR-induced liver injury and activated hepatic inflammatory responses and apoptosis in vivo and in vitro. Conversely, RGS14 overexpression exerted the opposite effect of the RGS14-deficient models. Phosphorylation of TGF-ß-activated kinase 1 (TAK1) and its downstream effectors c-Jun N-terminal kinase (JNK) and p38 increased in the liver tissues of RGS14-KO mice but was repressed in those of RGS14-TG mice. Furthermore, inhibition of TAK1 phosphorylation rescued the effect of RGS14 deficiency on JNK and p38 activation, thus blocking the inflammatory responses and apoptosis. CONCLUSIONS: RGS14 plays a protective role in hepatic IR by inhibiting activation of the TAK1-JNK/p38 signaling pathway. This may be a potential therapeutic strategy for reducing incidences of hepatic IRI in the future.

[Therapeutic effect of recombinant human growth hormone on children with growth hormone deficiency and different pituitary developmental conditions: a prospective study]. / é‡ç»„äººç”Ÿé•¿æ¿€ç´ æ²»ç–—ä¸åŒåž‚ä½“å‘è‚²çŠ¶å†µç”Ÿé•¿æ¿€ç´ ç¼ºä¹ç—‡æ‚£å„¿ç–—æ•ˆçš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To investigate the therapeutic effect of recombinant human growth hormone (rhGH) on children with growth hormone deficiency (GHD) and different pituitary developmental conditions. METHODS: A prospective study was performed on 90 children with GHD who were admitted to Xuchang Maternity and Child Health Hospital from June 2020 to December 2021. According to pituitary height on the median sagittal plane, they were divided into three groups: pituitary dysplasia group (n=45), normal pituitary group (n=31), and enlarged pituitary growth group (n=14). The changes in body height, growth velocity, height standard deviation score and serum levels of insulin-like growth factor binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) were examined after treatment in the above three groups, and the differences of the above indices before and after treatment were compared among the three groups. RESULTS: After treatment, all three groups had significant increases in body height, growth velocity, height standard deviation score, and the serum levels of IGFBP-3 and IGF-1 (P<0.05). Compared with the normal pituitary group, the pituitary dysplasia group and the enlarged pituitary growth group had significantly higher values in terms of the differences in body height, growth velocity, height standard deviation score, IGF-1, and IGFBP-3 before and after treatment (P<0.05). There was no significant difference in the incidence rate of adverse reactions among the three groups (P>0.05). CONCLUSIONS: In GHD children with different pituitary developmental conditions, rhGH can promote bone growth and increase body height, especially in children with pituitary dysplasia and pituitary hyperplasia, with good safety.

Organic Long Persistent Luminescence Through In Situ Generation of Cuprous(I) Ion Pairs in Ionic Solids.

Recent development of most organic long persistent luminescence (OLPL) systems employed binary or tertiary doping. However, the design strategies towards OLPL materials with hour-long afterglow duration are still quite limited. Here, we propose a novel OLPL system through melt-casting method with 0.1 mol % of CuI complexes: 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl BINAP-CuX (X=Cl, Br and I) doped into the triphenylphosphine (TPP) host. The charge separation was initiated prior to excitation through host coordination with CuI complexes, resulting in semi-free halogen ions and in situ generated CuI cations, which forms TPP + BINAP-CuX ionic pairs and subsequently ionic solids. The OLPL lifetime can be readily modulated by different halogen atoms and the afterglow can last up to more than 3 hours perceivable to human eyes. This is a rare example of OLPL initiated through host-guest coordination that could potentially expand the definition of OLPL systems and design strategies.

Photoresponsive Propeller-like Chiral AIE Copper(I) Clusters.

A pair of propeller-like chiral trinuclear CuI clusters (R/S-Cu3) with unique photoinduced fluorescence enhancement were prepared. R/S-Cu3 showed intense variable luminescence after UV light irradiation, which was attributed to the stepwise oxidation of ligand in the clusters. It exhibited typical aggregation-induced emission (AIE) (αAIE =17.3). Mechanism studies showed that metal cluster-centered (MCC) and triplet metal-to-ligand charge-transfer (3 MLCT) processes are the origin of the luminescence; the processes are regulated by a restriction of intramolecular motions mechanism in a different state. The chiral structure and AIE feature endow R/S-Cu3 with remarkable circularly polarized luminescence (glum =2×10-2 ) in the aggregated state. It shows good capability for producing reactive oxygen species. This work enriches the kinds of atomically precise AIE clusters, gains insight into their luminescence mechanism, and offers the prospect of application in multifunctional materials.

Configurationally Stable Platinahelicene Enantiomers for Efficient Circularly Polarized Phosphorescent Organic Light-Emitting Diodes.

Chiral materials with circularly polarized luminescence (CPL) are potentially applicable for 3D displays. In this study, by decorating the pyridinyl-helicene ligands with -CF3 and -F groups, the platinahelicene enantiomers featured superior configurational stability, as well as high sublimation yield (>90 %) and clear CPPL properties, with dissymmetry factors (|gPL |) of approximately 3.7×10-3 in solution and about 4.1×10-3 in doped film. The evaporated circularly polarized phosphorescent organic light-emitting diodes (CP-PhOLEDs) with two enantiomers as emitters exhibited symmetric CPEL signals with |gEL | of (1.1-1.6)×10-3 and decent device performances, achieving a maximum brightness of 11 590 cd m-2 , a maximum external quantum efficiency up to 18.81 %, which are the highest values among the reported devices based on chiral phosphorescent PtII complexes. To suppress the effect of reverse CPEL signal from the cathode reflection, the further implementation of semitransparent aluminum/silver cathode successfully boosts up the |gEL | by over three times to 5.1×10-3 .

Organic Room-Temperature Phosphorescence with Strong Circularly Polarized Luminescence Based on Paracyclophanes.

Pure organic materials with intrinsic room-temperature phosphorescence typically rely on heavy atoms or heteroatoms. Two different strategies towards constructing organic room-temperature phosphorescence (RTP) species based upon the through-space charge transfer (TSCT) unit of [2.2]paracyclophane (PCP) were demonstrated. Materials with bromine atoms, PCP-BrCz and PPCP-BrCz, exhibit RTP lifetime of around 100 ms. Modulating the PCP core with non-halogen-containing electron-withdrawing units, PCP-TNTCz and PCP-PyCNCz, successfully elongate the RTP lifetime to 313.59 and 528.00 ms, respectively, the afterglow of which is visible for several seconds under ambient conditions. The PCP-TNTCz and PCP-PyCNCz enantiomers display excellent circular polarized luminescence with dissymmetry factors as high as -1.2×10-2 in toluene solutions, and decent RTP lifetime of around 300 ms for PCP-TNTCz enantiomers in crystalline state.

Treatment of Hepatocellular Carcinoma with Tumor Thrombus with the Use of Iodine-125 Seed Strand Implantation and Transarterial Chemoembolization: A Propensity-Score Analysis.

PURPOSE: To evaluate the safety and efficacy of iodine-125 (125I) seed strand implantation in combination with transarterial chemoembolization for the treatment of hepatitis B-related unresectable hepatocellular carcinoma (HCC) with portal vein invasion. MATERIALS AND METHODS: From January 2013 to June 2016, 76 HCC patients with type II tumor thrombus were included in this single-center retrospective study. Twenty patients underwent 125I seed strand implantation combined with transarterial chemoembolization (group A; n = 20), while 56 patients underwent transarterial chemoembolization alone (group B; n = 56). The procedure-related and radiation complications were assessed. Overall survivals were compared by propensity-score analysis. RESULTS: The technique was successfully performed in all patients. The mean intended dose (r = 10 mm; z = 0; 240 days) was 62.6 ± 1.8 Gy. No grade 3 or 4 adverse events related to the procedure occurred in either group. After propensity-score-matching analysis, 19 patients were selected into each group, respectively. In the propensity-matching cohort, the median overall survival time was significantly longer in group A than in the group B (19 pairs; 28.0 ± 2.4 vs 8.7 ± 0.4 mo; P = .001). Treatment strategy, arterioportal shunt, and number of transarterial chemoembolization sessions were significant predictors of favorable overall survival time. CONCLUSIONS: 125I seed strand implantation combined with transarterial chemoembolization is a safe and effective treatment for HCC patients with portal vein invasion.

Peripheral Amplification of Multi-Resonance Induced Thermally Activated Delayed Fluorescence for Highly Efficient OLEDs.

Multi-resonance induced by boron and nitrogen atoms in opposite resonance positions endows a thermally activated delayed fluorescence (MR-TADF) emitter with a strikingly small full width at half maximum of only 26 nm and excellent photoluminescence quantum yield of up to 97.48 %. The introduction of a carbazole unit in the para position of the B-substituted phenyl-ring can significantly boost up the resonance effect without compromising the color fidelity, subsequently enhancing the performances of the corresponding pure blue TADF-OLED, with an outstanding external quantum efficiency (EQE) up to 32.1 % and low efficiency roll-off, making it one of the best TADF-OLEDs in the blue region to date. Furthermore, utilizing this material as host for a yellow phosphorescent emitter, the device also shows a significantly reduced turn-on voltage of 3.2 V and an EQEmax of 22.2 %.

Combination Therapies in the Management of Large (≥ 5 cm) Hepatocellular Carcinoma: Microwave Ablation Immediately Followed by Transarterial Chemoembolization.

PURPOSE: To evaluate the safety and efficacy of microwave (MW) ablation combined with transarterial chemoembolization in a single stage for the treatment of large (≥ 5 cm) hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From March 2013 to January 2015, 66 patients (54 men and 12 women; mean age, 54 y; range, 29-83 y) with 72 large HCC lesions were included in this study. Eighteen (27.3%) had Barcelona Clinic Liver Cancer class B disease, and 48 (72.7%) had class C disease. Seventy-nine percent of patients (n = 52) had hepatitis B virus infection. The average tumor size was 9.0 cm ± 3.9, ranging from 5 to 19 cm. MW ablation was performed under ultrasound guidance, immediately followed by chemoembolization. Local tumor response, progression-free survival (PFS), and overall survival (OS) were assessed. RESULTS: The technique was successfully performed in all patients. Complete response (CR) was achieved in 28 cases (42.4%), and partial response (PR) was achieved in 34 cases (51.5%) at 1 month after the procedure. The objective response rate (ie, CR plus PR) was 93.9%. Median PFS and OS times were 9 months and 21 months, respectively. The 6-, 12-, and 18-month OS rates were 93.9%, 85.3%, and 66.6%, respectively. Hemorrhage was detected in three patients and arteriovenous fistula in two patients after MW ablation; all were promptly treated with embolization. There were no liver abscesses, bile-duct injuries, or other major procedure-related complications. CONCLUSIONS: MW ablation immediately followed by chemoembolization is safe and effective in the treatment of large HCC lesions.

Downregulation of miR-145 associated with cancer progression and VEGF transcriptional activation by targeting N-RAS and IRS1.

MicroRNA-145 (miR-145) is downregulated in various tumor types. However, its mechanism in inhibiting tumor growth and angiogenesis remains to be elucidated. In this study, we found that miR-145 was significantly downregulated in the plasma and cancer tumor tissues of colorectal cancer (CRC) patients, and overexpression of miR-145 inhibited cell proliferation, migration and invasion. To understand the potential mechanism of miR-145 in inhibiting tumor growth, we showed that miR-145 blocked the activation of AKT and ERK1/2 pathways, and the expression of HIF-1 and VEGF via directly targeting N-RAS and IRS1, and VEGF is an important effector for tumor growth. Forced expression of N-RAS and IRS1 restored VEGF expression via transcriptional activation. MiR-145 also inhibited N-RAS and IRS1 expression to suppress AKT and ERK1/2 activation, and VEGF expression in mouse xenograft tumors. To test the clinical relevance of these results, we used 60 pairs of colorectal cancer tissues and adjacent normal tissues, analyzed the levels of miR-145, N-RAS and IRS1 expression in these tissues, and found that miR-145 levels were significantly inversely correlated with N-RAS and IRS1 levels in these colorectal cancer tissues, suggesting the important implication of our findings in translational application for colorectal cancer diagnostics and treatment in the future.

Transarterial infusion with gemcitabine and oxaliplatin for the treatment of unresectable pancreatic cancer.

The aim of this study was to evaluate the therapeutic efficacy and the safety of transarterial infusion (TAI) with gemcitabine and oxaliplatin in patients with unresectable pancreatic cancer (PC). After celiac arteriogram and super-mesenteric arteriography, 1000 mg/m gemcitabine and 100 mg/m oxaliplatin were infused through 4- or 5-Fr catheters in arteries supplying blood to the tumor. In cases in which the blood-supplying artery could be selectively catheterized, the infusion was performed through a 3-Fr catheter placed in the tumor-supplying artery. Therapeutic courses were repeated every 4 weeks. The tumor response, the overall survival, and adverse effects were monitored. Thirty-two patients with unresectable PC were enrolled in this study, including 20 male and 12 female patients. A total of 105 cycles of TAI (mean=3.3 cycles/patient) were performed. Of 32 patients, partial remission was achieved in eight (25.0%), stable disease in 13 (40.6%), and progressive disease in 11 (34.4%). The overall response rate was 25.0%. The median survival time was 10.0 months (range=4-21 months). Grade III-IV toxicity, vomiting, occurred with a rate of 21.9%. Grade I-II neutropenia, thrombocytopenia, peripheral nerve toxicity, elevated serum transaminases levels, and serum total bilirubin were observed. TAI with gemcitabine and oxaliplatin is well tolerated and highly effective in patients with unresectable PC.

Distinction and quantification of Panax polysaccharide extracts via attenuated total reflectance-Fourier transform infrared spectroscopy with first-order derivative processing.

Derivative spectroscopy is used to separate the small absorption peaks superimposed on the main absorption band, which is widely adopted in modern spectral analysis to increase both the valid spectral information and the identification accuracy. In this study, a method based on attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) with first-order derivative (FD) processing combined with chemometrics is proposed for rapid qualitative and quantitative analysis of Panax ginseng polysaccharides (PGP), Panax notoginseng polysaccharides (PNP), and Panax quinquefolius polysaccharides (PQP). First, ATR-FTIR with FD processing was used to establish the discriminant model combined with principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and linear discriminant analysis (LDA). After that, two-dimensional ATR-FTIR based on single-characteristic temperature as external interference (2D-sATR-FTIR) was established using ATR-FTIR with FD processing. Then, ATR-FTIR with FD processing was combined with PLS to establish and optimize the quantitative regression model. Finally, the established discriminant model and 2D-sATR-FTIR successfully distinguished PGP, PNP and PQP, and the optimal PLS regression model had a good prediction ability for the Panax polysaccharide extracts content. This strategy provides an efficient, economical and nondestructive method for the distinction and quantification of PGP, PNP and PQP in a short detection time.

Application of Cone-beam Computed Tomography in Interventional Therapies for Liver Malignancy: A Consensus Statement by the Chinese College of Interventionalists.

Despite its crucial role in interventional therapies for liver malignancy, cone-beam computed tomography (CBCT) has not yet been fully integrated into clinical practice due to several complicating factors, including nonstandardized operations and limited recognition of CBCT among interventional radiologists. In response, the Chinese College of Interventionalists has released a consensus statement aimed at standardizing and promoting the application of CBCT in the interventional therapies for liver malignancy. This statement summarizes CBCT scanning techniques, and operational standards, and highlights its potential applications in clinical practice.

Two Different Chiral Groups Based Thermally Activated Delayed Fluorescence Materials for Circularly Polarized OLEDs.

Circularly polarized organic light-emitting diodes (CP-OLEDs) hold significant promise for applications in 3D displays due to the ability to generate circularly polarized luminescence (CPL) directly. In this study, two pairs of circularly polarized thermally activated delayed fluorescence (CP-TADF) enantiomers, named RR/SS-ONCN and RS/SR-ONCN, were synthesized by integrating two distinct chiral groups into the dicyanobenzene unit. The RR/SS-ONCN and RS/SR-ONCN enantiomers show CPL properties with dissymmetry photoluminescence factors (|gPL|) of 1.3×10-3 and 2.0×10-3 in doped films, respectively. Notably, RR/SS-ONCN exhibit higher |gPL| values than that of RS/SR-ONCN, especially in doped films, indicating that when the configurations of the two chiral groups are identical, the |gPL| value of the CP-TADF materials can be enhanced, demonstrating a certain stacking effect. Moreover, the corresponding CP-OLEDs demonstrate good performances, achieving maximum external quantum efficiencies of up to 21.9 % and notable CP electroluminescence with |gEL| factors of up to 1.0×10-3.

Transarterial Chemoembolization with Epirubicin-Loaded Microspheres for Hepatocellular Carcinoma: A Prospective, Single-Arm, Multicenter, Phase 2 Study (STOPPER Trial).

PURPOSE: While the role of drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) is established, questions regarding appropriate bead size for use in patients remain. This trial evaluated the effectiveness and safety of DEB-TACE using small-size (≤ 100 µm) microspheres loaded with epirubicin. MATERIALS AND METHODS: This prospective, single-arm, multicenter study enrolled patients diagnosed with HCC who underwent DEB-TACE using 40 (range, 30-50), 75 (range, 60-90), or 100 (range, 75-125) µm epirubicin-loaded microspheres (TANDEM microspheres, Varian Medical). Bead size was at the discretion of treating physicians and based on tumor size and/or vascular structure. The primary outcome measure was 6-month objective response rate (ORR). Secondary outcome measures were 30-day and 3-month ORR, time to tumor progression and extrahepatic spread, proportion of progression-free survival and overall survival (OS) at one year, and incidence of treatment-associated adverse events. RESULTS: Data from 108 patients from ten centers was analyzed. Six-month ORR was 73.3 and 71.3% based on European association for the study of the liver (EASL) and modified response evaluation criteria in solid tumors (mRECIST) criteria, respectively. Thirty-day ORR was 79.6% for both EASL and mRECIST criteria with 3-month ORR being 80.0 and 81.0%, respectively, for each criteria. One-year PPF and OS rate were 60.3 and 94.3%. There was a total of 30 SAEs reported to be likely to definitely associated with microsphere (n = 9), epirubicin (n = 9), or procedure (n = 12) with none resulting in death. CONCLUSION: DEB-TACE using epirubicin-loaded small-sized (≤ 100 µm) microspheres demonstrates promising local tumor control and acceptable safety in patients with HCC. TRIAL REGISTRATION: Clinicaltrials.gov NCT03113955; registered April 14, 2017. Trial Registration Clinicaltrials.gov NCT03113955; registered April 14, 2017. LEVEL OF EVIDENCE: 2, Prospective, Non-randomized, Single-arm, study.

Arterial chemotherapy for hepatocellular carcinoma in China: consensus recommendations.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.

Damage to pig bile duct caused by intraluminal brachytherapy using a (125)I ribbon.

BACKGROUND: Stent occlusion by tumor ingrowth or overgrowth is the main cause of jaundice recurrence after metal stent insertion in patients with malignant obstructive jaundice (MOJ). The application of intraluminal brachytherapy (ILBT) in patients with MOJ results in local control of malignant tumors, which prolong stent patency. PURPOSE: To evaluate the safety of ILBT in pig bile ducts using ribbons of iodine-125 ((125)I) seeds. MATERIAL AND METHODS: Sixteen healthy pigs were randomly assigned to four groups of four pigs each. A (125)I seed ribbon was implanted into the common bile duct of each animal through an incision in the duct wall, and was fixed by suturing. The four groups of animals were sacrificed at 15, 30, 60, and 120 days after ribbon implantation, respectively. Serum bilirubin concentrations, alanine aminotransferase concentrations, and white blood cell counts before and after implantation were compared within each group. Pathological changes to the bile duct wall were observed using a light microscope. Morphological changes in biliary epithelial cells and organelles were observed with electron microscopy. RESULTS: (125)I ribbons were successfully implanted in all animals without surgery-related death. We found no significant difference in pre- and post-implant serum bilirubin, alanine aminotransferase, or white blood cell counts. Light and electron microscopy showed that the most severe bile duct damage occurred in the 15-day group, which exhibited necrosis and detachment of numerous epithelial cells, and infiltration of inflammatory cells. Repair and proliferation of the bile duct epithelium began 30 days after implantation and was nearly complete at 60 days. CONCLUSION: This study demonstrated the safety of ILBT using a (125)I ribbon in the pig bile duct. (125)I seed ribbons may be used in the treatment of MOJ in humans.

[Intrahepatic portosystemic shunt assisted by percutaneous transhepatic approach for treatment of portal vein thrombosis].

OBJECTIVE: To retrospectively analyze the safety and efficacy of mechanical thrombectomy combined with pharmacologic thrombolysis to treat non-acute and symptomatic portal vein thrombosis (PVT) using an intrahepatic portosystemic shunt (IPS) assisted by percutaneous transhepatic approach. METHODS: From April 2006 to May 2012, 18 patients with non-acute and symptomatic PVT were treated with balloon dilation, sheath-directed thrombus aspiration and continuous infusion of urokinase using the IPS assisted by percutaneous transhepatic approach. The significance of differences in the portosystemic gradient measured before and after therapy was assessed by paired samples t-test, and survival analysis was made by the Kaplan-Meier method. RESULTS: IPS was successfully created in all patients. The mean duration of the thrombolytic therapy was 65.3 +/- 29.5 h, and the mean concentration of urokinase used for the thrombolysis was 2324000 +/- 945000 U. Comparison of the mean portosystemic gradients showed a significant improvement in response to the therapy (before: 33.8 +/- 4.9 mm Hg vs. after: 15.4 +/- 2.1 mm Hg; P less than 0.001). The overall rate of clinical improvement was 94.4%. One patient died on day 2 post-therapy and another two patients experienced mild hepatic encephalopathy or right hemothorax, respectively, on day 5 post-therapy, with conservative medical management achieving complete recovery for both. The mean follow-up time was 18.6 +/- 17.5 months, during which only one patient died and five others experienced shunt dysfunction; all remaining patients showed maintenance of shunt patency without symptoms of recurrence. CONCLUSION: Mechanical thrombectomy combined with pharmacologic thrombolysis via the IPS assisted by percutaneous transhepatic approach is a safe and effective therapeutic option for patients with non-acute and symptomatic PVT.

Charged multivesicular body protein 2B ameliorates biliary injury in the liver from donation after cardiac death rats via autophagy with air-oxygenated normothermic machine perfusion.

Normothermic machine perfusion (NMP) could provide a curative treatment to reduce biliary injury in donation after cardiac death (DCD) donor livers; however, the underlying mechanisms remain poorly understood. In a rat model, our study compared air-oxygenated NMP to hyperoxygenated NMP and found that air-oxygenated NMP improved DCD functional recovery. Here, we found that the charged multivesicular body protein 2B (CHMP2B) expression was substantially elevated in the intrahepatic biliary duct endothelium of the cold-preserved rat DCD liver after air-oxygenated NMP or in biliary endothelial cells under hypoxia/physoxia. CHMP2B knockout (CHMP2B-/-) rat livers showed increased biliary injury after air-oxygenated NMP, indicated by decreased bile production and bilirubin level, elevated biliary levels of lactate dehydrogenase and gamma-glutamyl transferase. Mechanically, we demonstrated that CHMP2B was transcriptionally regulated by Kruppel-like transcription factor 6 (KLF6) and alleviated biliary injury through decreasing autophagy. Collectively, our results suggested that air-oxygenated NMP regulates CHMP2B expression through the KLF6, which reduces biliary injury by inhibiting autophagy. Targeting the KLF6-CHMP2B autophagy axis may provide a solution to reducing biliary injury in DCD livers undergoing NMP.