While neuroblastoma accounts for 15% of childhood tumor-related deaths, treatments against neuroblastoma remain scarce and mainly consist of cytotoxic chemotherapeutic drugs. Currently, maintenance therapy of differentiation induction is the standard of care for neuroblastoma patients in clinical, especially high-risk patients. However, differentiation therapy is not used as a first-line treatment for neuroblastoma due to low efficacy, unclear mechanism, and few drug options. Through compound library screening, we accidently found the potential differentiation-inducing effect of AKT inhibitor Hu7691. The protein kinase B (AKT) pathway is an important signaling pathway for regulating tumorigenesis and neural differentiation, yet the relation between the AKT pathway and neuroblastoma differentiation remains unclear. Here, we reveal the anti-proliferation and neurogenesis effect of Hu7691 on multiple neuroblastoma cell lines. Further evidence including neurites outgrowth, cell cycle arrest, and differentiation mRNA marker clarified the differentiation-inducing effect of Hu7691. Meanwhile, with the introduction of other AKT inhibitors, it is now clear that multiple AKT inhibitors can induce neuroblastoma differentiation. Furthermore, silencing AKT was found to have the effect of inducing neuroblastoma differentiation. Finally, confirmation of the therapeutic effects of Hu7691 is dependent on inducing differentiation in vivo, suggesting that Hu7691 is a potential molecule against neuroblastoma. Through this study, we not only define the key role of AKT in the progression of neuroblastoma differentiation but also provide potential drugs and key targets for the application of differentiation therapies for neuroblastoma clinically.

Tumor recurrence and metastasis after liver transplantation (LT) remains one of the most important factors that affect the outcome of LT for hepatocellular carcinoma (HCC). The diagnosis and treatment strategies in the era of precision medicine, including utilizing multi-omics, high-throughput gene sequencing analysis, big data and artificial intelligence to select the biomarkers which can accurately predict the prognosis after LT, evaluating the immune status comprehensively, inducing immune tolerance, providing effective prevention for patients at a high risk of recurrence with sensitive antitumor drugs and attaching importance to individualized treatment for recurrence and metastasis, may further improve the outcome of LT. Combined with experience and review of relevant research articles, the authors elaborate perioperative diagnosis and treatment strategies of LT for HCC, aiming to promote the application of precision medicine in the field of LT.

BACKGROUND: To determine the prevalence and prognostic impact of hepatopulmonary syndrome (HPS) in patients with unresectable hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). METHODS: Fifty-four patients with unresectable HCC undergoing TACE between December 2014 and December 2015 were prospectively screened for HPS and were followed up for a maximum of 2 years or until the end of this prospective study. RESULTS: Nineteen of the 54 (35.2%) patients were considered to have HPS, including one (5.3%) with severe HPS, nine (47.4%) with moderate HPS, and nine (47.4%) with mild HPS. The median overall survival (OS) was 10.1 (95% confidence interval [CI], 3.9-16.3) months for patients with HPS and 15.1 (95% CI, 7.3-22.9) months for patients without HPS, which is not a significant difference ( P  = 0.100). The median progression-free survival was also not significantly different between patients with and without HPS (5.2 [95% CI, 0-12.8] vs. 8.4 [95% CI, 3.6-13.1] months; P  = 0.537). In the multivariable Cox regression analyses, carbon monoxide diffusing capacity (hazard ratio [HR] = 1.033 [95% CI, 1.003-1.064]; P  = 0.028) and Child-Pugh class (HR = 1.815 [95% CI, 1.011-3.260]; P  = 0.046) were identified to be the independent prognostic factors of OS. CONCLUSION Mild or moderate HPS is common in patients with unresectable HCC undergoing TACE, but it does not seem to have a significant prognostic impact.
Humans ; Carcinoma, Hepatocellular/pathology* ; Chemoembolization, Therapeutic ; Prospective Studies ; Liver Neoplasms/pathology* ; Prognosis ; Hepatopulmonary Syndrome/therapy* ; Prevalence ; Treatment Outcome ; Retrospective Studies

Objective : To observe the effect of hydrogen sulfide( H2 S) on the expression of transforming growth factor⁃β1(TGF⁃ β1) , E ⁃cadherin (E⁃CAD) , Vimentin (VIM) , alpha⁃smooth muscle actin ( α ⁃SMA) during epithelial⁃mesenchymal transformation(EMT) , and to explore the anti⁃fibrosis mechanism of it. Methods : Sixty rats ( male SD) were randomly divided into control group, bleomycin group, NaHS + bleomycin group and prednisolone + bleomycin group , 15 rats per group. 5 rats of each group were sacrificed at random in 7th , 14th and 28th day. The degree of alveolitis and pulmonary fibrosis was observed . The expression of protein and mRNA of TGF⁃ β1 , E ⁃cad , VIM , α ⁃SMA were determined by Immunohistochemi stry and RT⁃PCR. Results : ① HE and Masson staining showed that the lung tissue of fibrosis had the lowest degree in control group. and the most severe in bleomycin group. The lung tissue of NaHS + bleomycin group and prednisolone + bleomycin group also had alveolitis and fibrosis changes , but the degree Were significantly less than bleomycin group. ② The mRNA and protein expression levels of TGF⁃ β1 , VIM and α ⁃SMA in bleomycin group, NaHS + bleomycin group and prednisolone + bleomycin group were all higher than that in control group at 7th , 14th and 28th day ( P < 0. 05 ) , while the expression levels of them in NaHS + bleomycin group and prednisolone + bleomycin group were all lower than that in bleomycin groupat each time (P < 0. 05) , which was significant at 28th day in NaHS + bleomycin. ③ The mRNA and protein expression levels of E ⁃Cad in bleomycin group, NaHS + bleomycin group and prednisolone + bleomycin group were all lower than that in control group at 7th , 14th and 28th day(P < 0. 05) , but the expression levels of E ⁃Cad in⁃NaHS + bleomycin group and prednisolone + bleomycin group were higher than that in bleomycin group at each time(P < 0. 05) , which was significant at 28th day in NaHS + bleomycin. Conclusion H2 S can reduce the degree of pulmonary fibrosis in rats , its mechanism may be related to the down⁃regulation of TGF⁃ β1and the inhibition of the EMT , which can enhance the expression of E ⁃cad and reduce the expression of TGF⁃ β1 , VIM and α ⁃SMA.

Objective:To explore the risk factors influencing the prognosis for patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation and summarize the relevant diagnostic and therapeutic experiences.Methods:The clinicopathological features with diagnosis and treatment plan of 102 recurrent HCC patients fulfilling the Fudan Criteria were compared for survival rate (univariate analysis) and independent prognostic indicators were obtained by Cox multivariate analysis.Results:The 1/3/5-year overall survival rates were 92.2%, 48.6% and 34.6% and the 1/3/5-year survival rates with tumor were 63.2%, 31.0% and 16.7% respectively. Cox regression analysis indicated that patient age, whether tumor can be surgically resected or not and personalized diagnostic & therapeutic plan based upon targeted therapy were independent prognostic factors affecting the overall survival rates and survival rates with tumor.Conclusions:Although HCC recurrence and metastasis after liver transplantation seriously influence patient prognosis, satisfactory outcomes may be obtained for some patients through active, effective and precise managements.

Dendritic cell-based cancer vaccines (DC vaccines) have been proved efficient and safe in immunotherapy of various cancers, including melanoma, ovarian and prostate cancer. However, the clinical responses were not always satisfied. Here we proposed a novel strategy to prepare DC vaccines. In the present study, a fusion protein SNU containing a secretin-penetratin (SecPen) peptide, NY-ESO-1 and ubiquitin was designed and expressed. To establish the DC vaccine (DC-SNU), the mouse bone marrow-derived DCs (BMDCs) were isolated, pulsed with SNU and maturated with cytokine cocktail. Then peripheral blood mononuclear cells (PBMCs) from C57BL/6 mice inoculated intraperitoneally with DC-SNU were separated and cocultured with MC38/MC38

Objective:To investigate the preventive efficacy of pirfenidone in esophageal stent-related restenosis and the related underlying mechanisms.Methods:Twenty-four rats underwent esophageal stent placement were included in this study. The rats were randomly assigned to three groups, with 8 rats in each group. The three groups were set to receive placebo, 150 mg/kg pirfenidone and 300 mg/kg pirfenidone daily by oral administration for 28 days, respectively. Twenty-eight days after stent placement, the stented esophagi were harvested for histological examinations. The number of epithelial layers, the thickness of submucosal fibrosis, the percentage of granulation tissue area, the degree of inflammatory cell infiltration, the degree of collagen deposition, and the α-SMA staining scores were evaluated. One-way ANOVA was performed for the statistical comparison of the number of epithelial layers, the degree of inflammatory cell infiltration, the degree of collagen deposition and the α-SMA staining scores among these three groups. The Kruskal-Wallis H test was used for comparison of the thickness of submucosal fibrosis and the percentage of granulation tissue area among the three groups. Results:Gross pathological findings showed that both pirfenidone groups had significantly less luminal fibrotic tissue formation and restenosis than placebo group. The percentage of granulation tissue areas in placebo group, 150 mg/kg and 300 mg/kg pirfenidone groups were 57.23%±25.68%, 21.80%±6.65% and 12.18%±6.37%, respectively. Both pirfenidone groups showed significantly less granulation tissue areas than placebo group ( P<0.01). The degree of inflammatory cell infiltration, the degree of collagen deposition and the α-SMA staining scores were 3.28±0.55, 3.38±0.63 and 2.75±0.38 in placebo group, 2.30±0.46, 2.36±0.58 and 2.00±0.42 in 150 mg/kg pirfenidone group, and 1.86±0.38, 1.91±0.41 and 1.57±0.28 in 300 mg/kg pirfenidone group, respectively. Both pirfenidone groups showed significantly less inflammatory cell infiltration, collagen deposition and α-SMA staining scores than placebo group ( P<0.01). Conclusion:Pirfenidone can suppress esophageal stent-related restenosis in rats by significantly inhibiting inflammation, myofibroblast activation and proliferation, and fibrotic tissue formation.

Cholangiocarcinoma (CCA) has emerged as an intractable cancer with scanty therapeutic regimens. The aberrant activation of Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are reported to be common in CCA patients. However, the underpinning mechanism remains poorly understood. Deubiquitinase (DUB) is regarded as a main orchestrator in maintaining protein homeostasis. Here, we identified Josephin domain-containing protein 2 (JOSD2) as an essential DUB of YAP/TAZ that sustained the protein level through cleavage of polyubiquitin chains in a deubiquitinase activity-dependent manner. The depletion of JOSD2 promoted YAP/TAZ proteasomal degradation and significantly impeded CCA proliferation

Objective:To discuss the safety and feasibility of transradial access (TRA) in performing peripheral arterial intervention.Methods:The clinical data of the patients underwent peripheral vascular intervention via TRA in our hospital from September 2017 to March 2019 were reviewed. The success rate of radial artery puncture and subsequent operation after puncture, and related postoperative complications within 30 days were analyzed.Results:The clinical data of 112 peripheral arterial intervention procedures via TRA performed on 106 patients were reviewed, including transcatheter arterial chemoembolization in 83 cases, bronchial arterial infusion in 4 cases, pelvic tumor embolization in 11 cases and 14 other cases. The success rate of all interventional punctures was 97.3% (109/112), the operative success rate of interventional procedures was 98.2% (107/109). The TRA operation was failed in 5 patients, who were then converted to receive the femoral artery puncture and complete successfully. The severe complication of the operation was aortic dissection (2 cases). Minor complications included 2 cases of radial artery occlusion, radial artery spasm, arm pain and puncture point hematoma for each case. The severe complication and the minor complication rates were 1.8% (2/112) and 4.5% (5/112), respectively. Sixteen emergency operations were performed successfully, and no complication occurred.Conclusion:The TRA is a clinically safe and feasible approach for peripheral arterial interventional procedure.

Objective:To discuss the safety and feasibility of transradial access (TRA) in performing peripheral arterial intervention.Methods:The clinical data of the patients underwent peripheral vascular intervention via TRA in our hospital from September 2017 to March 2019 were reviewed. The success rate of radial artery puncture and subsequent operation after puncture, and related postoperative complications within 30 days were analyzed.Results:The clinical data of 112 peripheral arterial intervention procedures via TRA performed on 106 patients were reviewed, including transcatheter arterial chemoembolization in 83 cases, bronchial arterial infusion in 4 cases, pelvic tumor embolization in 11 cases and 14 other cases. The success rate of all interventional punctures was 97.3% (109/112), the operative success rate of interventional procedures was 98.2% (107/109). The TRA operation was failed in 5 patients, who were then converted to receive the femoral artery puncture and complete successfully. The severe complication of the operation was aortic dissection (2 cases). Minor complications included 2 cases of radial artery occlusion, radial artery spasm, arm pain and puncture point hematoma for each case. The severe complication and the minor complication rates were 1.8% (2/112) and 4.5% (5/112), respectively. Sixteen emergency operations were performed successfully, and no complication occurred.Conclusion:The TRA is a clinically safe and feasible approach for peripheral arterial interventional procedure.