Objective To evaluate the effective and safety of ultrasound-guided percutaneous portal vein guide wire placement adjunct to thrombolytic catheter,which treating portal vein thrombosis after liver transplantation.Methods From Jan 2012 to Dec 2015,a total of 6 patients (5 male,1 female,average age 50.6 years old,age range 41-65 years old) with portal vein thrombosis after liver transplantation were retrospectively studied.The diagnosis was confirmed by contrast enhanced ultrasound (CEUS) with hypoechonic and no enhancement in portal vein.With ultrasound-guided a 18-guage guide wire was placed in right branch of portal vein,and a guidewire was placement.After exchanging the catheter,the thrombosis was confirmed again by venography.A thrombolytic catheter was placed and local thrombolysis therapy was performed.Results The guidewires were successfully placed in 6 patients.The thrombolytic catheters were successfully placed in 5 patients (day 2-60 after operation),and failed in 1 patient (9 years after operation).With 5-11 days urokinase injection,the patency of portal vein was found in 5 patients,of which 4 patients was treated by angioplasty and stent placement.With 16-31 months follow-up,the patency of portal vein was maintained.Neither server complication nor related-death was occurred.Conclusions Ultrasound-guided percutaneous portal vein guide wire placement adjuncts thrombolytic catheter is effective and safety for treating portal vein thrombosis after liver transplantation.

OBJECTIVE:To systematically review the efficacy and safety of insulin glargine versus insulin detemir in the treat-ment of type 2 diabetes,and provide evidence-based reference for clinical treatment. METHODS:Retrieved from PubMed,EM-Base,Cochrane Library,CBM,CJFD,VIP and Wanfang database,randomized controlled trials (RCT) about the clinical efficacy and safety of insulin glargine versus insulin detemir in the treatment of type 2 diabetes were collected. Meta-analysis was performed by using Rev Man 5.2 software after data extraction and quality evaluation by Cochrane 5.1.0. RESULTS:A total of 18 RCTs,in-volving 3 638 patients were included. Results of Meta-analysis showed there was no significant difference in reducing glycosylated hemoglobin[MD=0.08,95%CI (-0.01,0.17),P=0.09];fasting blood glucose level in insulin glargine group was significantly lower thaninsulin detemir,the difference was statistically significant [MD=0.15,95%CI(0.03,0.27),P=0.02]. And there was no significant difference in the incidence of hypoglycemia [OR=0.97,95%CI(0.91,1.03),P=0.25];the degree of body mass gain ininsulin detemir was significantly lower than insulin glargine group [MD=-0.95,95%CI(-1.06,-0.85),P=0.003],but the in-cidence of injection site reactions was significantly higher than insulin glargine group [OR=2.28,95%CI(1.16,4.50),P=0.02],the differences were statistically significant. CONCLUSIONS:The insulin glargine has better efficacy,than insulin detemir with lower incidence of injection site reactions but higher degree of body mass gain than insulin detemir in the treatment of type 2 diabetes.

Purpose: This study aimed to investigate the clinicopathologic features and mutational landscape of patients with hepatitis B virus (HBV)–related advanced hepatocellular carcinomas (HCC) undergoing transcatheter arterial chemoembolization (TACE). Materials and Methods: From January 2017 to December 2018, 38 patients newly diagnosed with HBV-related advanced HCC were enrolled in the final analysis. Their pathological tissues and corresponding blood samples before TACE treatment were collected for whole-exome sequencing. Response to TACE was evaluated at 1-3 months after two consecutive use of TACE. Predictive factors were analyzed by univariate and multivariate analyses in a bivariate Logistic regression model. Enrichment of related pathways of all driver genes were acquired using the gene set enrichment analysis (GSEA). Results: Among 38 patients, 23 (60.5%) exhibited TACE failure/refractoriness. Patients with TACE failure/refractoriness showed higher frequency of TP53 mutation than their counterparts (p=0.020). Univariate and multivariate analyses showed that only vascular invasion and TP53 mutation were significantly correlated with TACE failure/refractoriness in HBV-related advanced HCC. Of the 16 patients without vascular invasion, eight (50.0%) had TP53 mutations, and TP53 mutation was associated with TACE failure/refractoriness (p=0.041). Moreover, GSEA showed that mitogen-activated protein kinase and apoptosis pathways induced by TP53 mutation were possibly associated with TACE failure/refractoriness. Conclusion Our study suggested that TP53 mutation was independently related with TACE efficacy, which may work via mitogen-activated protein kinase and apoptosis pathways. These findings may provide evidence to help distinguish patients who will particularly benefit from TACE from those who require more personalized therapeutic regimens and rigorous surveillance in HBV-related advanced HCC.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Metabolic reprogramming, a newly recognized trait of tumor biology, is an intensively studied prospect for oncology medicines. For numerous tumors and cancer cell subpopulations, oxidative phosphorylation (OXPHOS) is essential for their biosynthetic and bioenergetic functions. Cancer cells with mutations in isocitrate dehydrogenase 1 (IDH1) exhibit differentiation arrest, epigenetic and transcriptional reprogramming, and sensitivity to mitochondrial OXPHOS inhibitors. In this study, we report that berberine, which is widely used in China to treat intestinal infections, acted solely at the mitochondrial electron transport chain (ETC) complex I, and that its association with IDH1 mutant inhibitor (IDH1^mi) AG-120 decreased mitochondrial activity and enhanced antileukemic effect in vitro andin vivo. Our study gives a scientific rationale for the therapy of IDH1 mutant acute myeloid leukemia (AML) patients using combinatory mitochondrial targeted medicines, particularly those who are resistant to or relapsing from IDH1^mi.
Humans ; Oxidative Phosphorylation ; Berberine ; Electron Transport ; Mitochondria ; Leukemia, Myeloid, Acute ; Isocitrate Dehydrogenase

Cryoablation (CRA) and microwave ablation (MWA) are two main local treatments for hepatocellular carcinoma (HCC). However, which one is more curative and suitable for combining with immunotherapy is still controversial. Herein, CRA induced higher tumoral PD-L1 expression and more T cells infiltration, but less PD-L1^highCD11b⁺ myeloid cells infiltration than MWA in HCC. Furthermore, CRA had better curative effect than MWA for anti-PD-L1 combination therapy in mouse models. Mechanistically, anti-PD-L1 antibody facilitated infiltration of CD8⁺ T cells by enhancing the secretion of CXCL9 from cDC1 cells after CRA therapy. On the other hand, anti-PD-L1 antibody promoted the infiltration of NK cells to eliminate PD-L1^highCD11b⁺ myeloid cells by antibody-dependent cell-mediated cytotoxicity (ADCC) effect after CRA therapy. Both aspects relieved the immunosuppressive microenvironment after CRA therapy. Notably, the wild-type PD-L1 Avelumab (Bavencio), compared to the mutant PD-L1 atezolizumab (Tecentriq), was better at inducing the ADCC effect to target PD-L1^highCD11b⁺ myeloid cells. Collectively, our study uncovered the novel insights that CRA showed superior curative effect than MWA in combining with anti-PD-L1 antibody by strengthening CTL/NK cell immune responses, which provided a strong rationale for combining CRA and PD-L1 blockade in the clinical treatment for HCC.