Predicting histological grade in pediatric glioma using multiparametric radiomics and conventional MRI features.

Prediction of glioma is crucial to provide a precise treatment plan to optimize the prognosis of children with glioma. However, studies on the grading of pediatric gliomas using radiomics are limited. Meanwhile, existing methods are mainly based on only radiomics features, ignoring intuitive information about tumor morphology on traditional imaging features. This study aims to utilize multiparametric magnetic resonance imaging (MRI) to identify high-grade and low-grade gliomas in children and establish a classification model based on radiomics features and clinical features. A total of 85 children with gliomas underwent tumor resection, and part of the tumor tissue was examined pathologically. Patients were categorized into high-grade and low-grade groups according to World Health Organization guidelines. Preoperative multiparametric MRI data, including contrast-enhanced T1-weighted imaging, T2-weighted imaging, T2-weighted fluid-attenuated inversion recovery, diffusion-weighted images, and apparent diffusion coefficient sequences, were obtained and labeled by two radiologists. The images were preprocessed, and radiomics features were extracted for each MRI sequence. Feature selection methods were used to select radiomics features, and statistically significant clinical features were identified using t-tests. The selected radiomics features and conventional MRI features were used to train the AutoGluon models. The improved model, based on radiomics features and conventional MRI features, achieved a balanced classification accuracy of 66.59%. The cross-validated areas under the receiver operating characteristic curve for the classifier of AutoGluon frame were 0.8071 on the test dataset. The results indicate that the performance of AutoGluon models can be improved by incorporating conventional MRI features, highlighting the importance of the experience of radiologists in accurately grading pediatric gliomas. This method can help predict the grade of pediatric glioma before pathological examination and assist in determining the appropriate treatment plan, including radiotherapy, chemotherapy, drugs, and gene surgery.

Air-Stable and Low-Cost High-Voltage Hydrated Eutectic Electrolyte for High-Performance Aqueous Aluminum-Ion Rechargeable Battery with Wide-Temperature Range.

Aqueous aluminum-ion batteries (AAIBs) are considered as a promising alternative to lithium-ion batteries due to their large theoretical capacity, high safety, and low cost. However, the uneven deposition, hydrogen evolution reaction (HER), and corrosion during cycling impede the development of AAIBs, especially under a harsh environment. Here, a hydrated eutectic electrolyte (AATH40) composed of Al(OTf)3, acetonitrile (AN), triethyl phosphate (TEP), and H2O was designed to improve the electrochemical performance of AAIBs in a wide temperature range. The combination of molecular dynamics simulations and spectroscopy analysis reveals that AATH40 has a less-water-solvated structure [Al(AN)2(TEP)(OTf)2(H2O)]3+, which effectively inhibits side reactions, decreases the freezing point, and extends the electrochemical window of the electrolyte. Furthermore, the formation of a solid electrolyte interface, which effectively inhibits HER and corrosion, has been demonstrated by X-ray photoelectron spectroscopy, X-ray diffraction tests, and in situ differential electrochemical mass spectrometry. Additionally, operando synchrotron Fourier transform infrared spectroscopy and electrochemical quartz crystal microbalance with dissipation monitoring reveal a three-electron storage mechanism for the Al//polyaniline full cells. Consequently, AAIBs with this electrolyte exhibit improved cycling stability within the temperature range of -10-50 °C. This present study introduces a promising methodology for designing electrolytes suitable for low-cost, safe, and stable AAIBs over a wide temperature range.

The clinical significance and application of the peri-implant phenotype in dental implant surgery: a narrative review.

Background and Objective: In recent years, the concept of the peri-implant phenotype has become a new standard for the clinical evaluation of the soft and hard tissues surrounding dental implants. Improving this phenotype enhances the likelihood of achieving long-term favorable results and is a necessary consideration during implant planning. Stable peri-implant tissue support is also crucial for the functional and aesthetic value of implant restoration. Herein, the authors review the clinical significance of the peri-implant phenotype and assess the timing of treatment strategies for improving peri-implant phenotype elements. Methods: A literature search was performed to retrieve papers on peri-implant tissue management and clinical outcomes published up to November 24th, 2022 in PubMed, Web of Science, EMBASE, and Scopus. Key Content and Findings: The optimal time to improve peri-implant bone thickness (PBT) is with augmentation procedures before implant surgery or at the same time as first-stage surgery. Similarly, issues associated with keratinized mucosa width (KMW) and mucosal thickness (MT) should be addressed before final restoration. The establishment of supracrestal tissue height (STH) depends on the MT and implant depth of the patient. Furthermore, special attention should be paid to the effect of the peri-implant phenotype on the prognosis of immediate implant placement in the aesthetic zone. Conclusions: The long-term success of implant restoration depends on careful planning that considers appropriate interventions for improving the peri-implant phenotype at different stages of treatment to reduce iatrogenic variables.

Safety and efficacy of the SeparGateTM balloon-guiding catheter in neurointerventional surgery: A prospective, multicenter, single-arm clinical trial.

Objective: To evaluate the safety and efficacy of the SeparGate™ balloon-guiding catheter (BGC) for blocking flow and delivering devices in neurointerventional surgery. Method: This prospective multicenter single-arm trial enrolled patients who received BGC adjuvant therapy to provide temporary blood flow arrest of the supra-aortic arch arteries and their branch vessels in interventional therapy. The primary endpoint was immediate procedural success rate in flow arrest, device delivery, and withdrawal. The efficacy endpoints were intraoperative product performance, including rigidity, smoothness, fracture resistance of the catheter wall, catheter push performance, compatibility and radiopaque display, integrity, adhesion thrombus after withdrawal and balloon rupture. The safety endpoints were adverse and serious adverse events associated with the test device and serious adverse events resulting in death or serious health deterioration. Result: A total of 129 patients were included; of them, 128 were analyzed in the full analysis set (FAS) and per protocol set (PPS). Immediate procedural success was achieved in 97.7% of patients with FAS and PPS. The lower bound of the 95% confidence interval was 94.6%, higher than the preset efficacy margin of 94%. Device-related adverse events occurred in 2 (1.6%) cases. One was mild adverse event of vasospasm, which resolved spontaneously. The other was serious adverse event of dissection aggravation, which was treated with stenting angioplasty. No device defects were observed. Conclusion: In neurointerventional surgery, the SeparGate™ BGC can be used to temporarily block the flow of the supra-aortic arch arteries and their branch vessels and guide the interventional device to the target vascular position.

ID proteins promote the survival and primed-to-naive transition of human embryonic stem cells through TCF3-mediated transcription.

Inhibition of DNA binding proteins 1 and 3 (ID1 and ID3) are important downstream targets of BMP signalling that are necessary for embryonic development. However, their specific roles in regulating the pluripotency of human embryonic stem cells (hESCs) remain unclear. Here, we examined the roles of ID1 and ID3 in primed and naive-like hESCs and showed that ID1 and ID3 knockout lines (IDs KO) exhibited decreased survival in both primed and naive-like state. IDs KO lines in the primed state also tended to undergo pluripotent dissolution and ectodermal differentiation. IDs KO impeded the primed-to-naive transition (PNT) of hESCs, and overexpression of ID1 in primed hESCs promoted PNT. Furthermore, single-cell RNA sequencing demonstrated that ID1 and ID3 regulated the survival and pluripotency of hESCs through the AKT signalling pathway. Finally, we showed that TCF3 mediated transcriptional inhibition of MCL1 promotes AKT phosphorylation, which was confirmed by TCF3 knockdown in KO lines. Our study suggests that IDs/TCF3 acts through AKT signalling to promote survival and maintain pluripotency of both primed and naive-like hESCs.

Metabolic Dysfunction-associated Fatty Liver Disease is Associated with Greater Impairment of Lung Function than Nonalcoholic Fatty Liver Disease.

Background and Aims: We compared lung function parameters in nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD), and examined the association between lung function parameters and fibrosis severity in MAFLD. Methods: In this cross-sectional study, we randomly recruited 2,543 middle-aged individuals from 25 communities across four cities in China during 2016 and 2020. All participants received a health check-up including measurement of anthropometric parameters, biochemical variables, liver ultrasonography, and spirometry. The severity of liver disease was assessed by the fibrosis (FIB)-4 score. Results: The prevalence of MAFLD was 20.4% (n=519) and that of NAFLD was 18.4% (n=469). After adjusting for age, sex, adiposity measures, smoking status, and significant alcohol intake, subjects with MAFLD had a significantly lower predicted forced vital capacity (FVC, 88.27±17.60% vs. 90.82±16.85%, p<0.05) and lower 1 s forced expiratory volume (FEV1, 79.89±17.34 vs. 83.02±16.66%, p<0.05) than those with NAFLD. MAFLD with an increased FIB-4 score was significantly associated with decreased lung function. For each 1-point increase in FIB-4, FVC was diminished by 0.507 (95% CI: -0.840, -0.173, p=0.003), and FEV1 was diminished by 0.439 (95% CI: -0.739, -0.140, p=0.004). The results remained unchanged when the statistical analyses was performed separately for men and women. Conclusions: MAFLD was significantly associated with a greater impairment of lung function parameters than NAFLD.

Predictors of futile recanalization in patients undergoing endovascular treatment in the DIRECT-MT trial.

BACKGROUND: Futile recanalization-when patients have a successful recanalization but fail to achieve a satisfactory functional outcome- is a common phenomenon of endovascular treatment of acute ischemic stroke (AIS). The present study aimed to identify the predictors of futile recanalization in AIS patients who received endovascular treatment. METHODS: This is a post-hoc analysis of the DIRECT-MT trial. Demographics, clinical characteristics, acute stroke workflow interval times, biochemical parameters, and imaging characteristics were compared between futile and meaningful recanalization groups. Multivariate analysis was performed to identify the predictors of futile recanalization. RESULTS: Futile recanalization was observed in 277 patients. In multivariable logistic regression analysis, older age (p<0.001), higher baseline systolic blood pressure (SBP) (p=0.032), incomplete reperfusion defined by extended Thrombolysis In Cerebral Infarction (eTICI) grades (p=0.020), and larger final infarct volume (FIV) (p<0.001) were independent predictors of futile recanalization. CONCLUSIONS: Old age, high baseline SBP, incomplete reperfusion defined by eTICI, and large FIV were independent predictors of futile recanalization after endovascular therapy for AIS.

Comparing the efficacy and safety of the Skyflow device with those of the Solitaire FR stent in patients with acute ischemic stroke: a prospective, multicenter, randomized, non-inferiority clinical trial.

BACKGROUND: Mechanical thrombectomy is the standard treatment for acute ischemic stroke (AIS) with large vessel occlusion (LVO) in the anterior circulation. This trial aimed to indicate whether Skyflow, a new thrombectomy device, could achieve the same safety and efficacy as Solitaire FR in the treatment of AIS. METHODS: This study was a prospective, multicenter, randomized, single blind, parallel, positive controlled, non-inferiority clinical trial. Patients with intracranial anterior circulation LVO within 8 hours from onset were included to receive thrombectomy treatment with either the Skyflow or Solitaire FR stent retriever. The primary endpoint was the rate of successful reperfusion (modified Treatment In Cerebral Infarction (mTICI) ≥2b) after the operation. The safety endpoints were the rate of symptomatic intracranial hemorrhage (sICH) and subarachnoid hemorrhage (SAH) at 24 hours after operation. RESULTS: A total of 95 and 97 patients were involved in the Skyflow group and Solitaire FR group, respectively. A successful reperfusion (mTICI ≥2b) was finally achieved in 84 (88.4%) patients in the Skyflow group and 80 (82.5%) patients in the Solitaire FR group. Skyflow was non-inferior to Solitaire FR in regard to the primary outcome, with the criterion of a non-inferiority margin of 12.5% (p=0.0002) after being adjusted for the combined center effect and the National Institutes of Health Stroke Scale (NIHSS) score. The rate of periprocedural sICH and SAH did not differ significantly between the two groups. CONCLUSION: Endovascular thrombectomy with the Skyflow stent retriever was non-inferior to Solitaire FR with regard to successful reperfusion in AIS due to LVO (with a pre-specified non-inferiority margin of 12.5%).

Conditioned medium derived from 3D tooth germs: A novel cocktail for stem cell priming and early in vivo pulp regeneration.

OBJECTIVES: Conditioned medium (CM) from 2D cell culture can mitigate the weakened regenerative capacity of the implanted stem cells. However, the capacity of 3D CM to prime dental pulp stem cells (DPSCs) for pulp regeneration and its protein profile are still elusive. We aim to investigate the protein profile of CM derived from 3D tooth germs, and to unveil its potential for DPSCs-based pulp regeneration. MATERIALS AND METHODS: We prepared CM of 3D ex vivo cultured tooth germ organs (3D TGO-CM) and CM of 2D cultured tooth germ cells (2D TGC-CM) and applied them to prime DPSCs. Influences on cell behaviours and protein profiles of CMs were compared. In vivo pulp regeneration of CMs-primed DPSCs was explored using a tooth root fragment model on nude mice. RESULTS: TGO-CM enhanced DPSCs proliferation, migration, in vitro mineralization, odontogenic differentiation, and angiogenesis performances. The TGO-CM group generated superior pulp structures, more odontogenic cells attachment, and enhanced vasculature at 4 weeks post-surgery, compared with the TGC-CM group. Secretome analysis revealed that TGO-CM contained more odontogenic and angiogenic growth factors and fewer pro-inflammatory cytokines. Mechanisms leading to the differential CM profiles may be attributed to the cytokine-cytokine receptor interaction and PI3K-Akt signalling pathway. CONCLUSIONS: The unique secretome profile of 3D TGO-CM made it a successful priming cocktail to enhance DPSCs-based early pulp regeneration.

Association of Preoperative Coagulability With Incidence and Extent of Portal Vein Tumor Thrombus and Survival Outcomes in Hepatocellular Carcinoma After Hepatectomy: A Large-Scale, Multicenter Study.

BACKGROUND: Occurrence of portal vein tumor thrombus (PVTT) worsens the outcomes of hepatocellular carcinoma (HCC) and imparts high economic burden on society. Patients with high risks of having hypercoagulation are more likely to experience thrombosis. Herein, we examined how preoperative international normalized ratio (INR) was related to the incidence and extent of PVTT, and associated with survival outcomes in HCC patients following R0 liver resection (LR). METHODS: Patients with HCC and PVTT were enrolled from six major hospitals in China. The overall survival (OS) and recurrence-free survival (RFS) rates of individuals with different INR levels were assessed with Cox regression analysis as well as Kaplan-Meier method. RESULTS: This study included 2207 HCC patients, among whom 1005 patients had concurrent PVTT. HCC patients in the Low INR group had a significantly higher incidence of PVTT and more extensive PVTT than the Normal and High INR groups (P<0.005). Of the 592 HCC subjects who had types I/II PVTT following R0 LR, there were 106 (17.9%), 342 (57.8%) and 144 (24.3%) patients in the High, Normal and Low INR groups, respectively. RFS and OS rates were markedly worse in patients in the Low INR group relative to those in the Normal and High INR groups (median RFS, 4.87 versus 10.77 versus 11.40 months, P<0.001; median OS, 6.30 versus 11.83 versus 12.67 months, P<0.001). CONCLUSION: Preoperative INR influenced the incidence and extent of PVTT in HCC. Particularly, patients with HCC and PVTT in the Low INR group had worse postoperative prognosis relative to the High and Normal INR groups.

m6A RNA methylation-mediated HNF3γ reduction renders hepatocellular carcinoma dedifferentiation and sorafenib resistance.

Hepatocyte nuclear factor 3γ (HNF3γ) is a hepatocyte nuclear factor, but its role and clinical significance in hepatocellular carcinoma (HCC) remain unclear. Herein, we report that HNF3γ expression is downregulated in patient HCC and inversely correlated with HCC malignancy and patient survival. Moreover, our data suggested that the HNF3γ reduction in HCC could be mediated by METTL14-dependent m6A methylation of HNF3γ mRNA. HNF3γ expression was increased during hepatic differentiation and decreased in dedifferentiated HCC cells. Interestingly, HNF3γ delivery promoted differentiation of not only HCC cells but also liver CSCs, which led to suppression of HCC growth. Mechanistic analysis suggested an HNF3γ-centered regulatory network that includes essential liver differentiation-associated transcription factors and functional molecules, which could synergistically facilitate HCC cell differentiation. More importantly, enforced HNF3γ expression sensitized HCC cells to sorafenib-induced growth inhibition and cell apoptosis through transactivation of OATP1B1 and OATP1B3 expression, which are major membrane transporters for sorafenib uptake. Clinical investigation showed that patient-derived HCC xenografts with high HNF3γ expression exhibited a sorafenib response and patients with high HCC HNF3γ levels benefited from sorafenib therapy. Together, these results suggest that HNF3γ plays an essential role in HCC differentiation and may serve as a therapeutic target and predictor of sorafenib benefit in patients.

[METTL14 as a predictor of postoperative survival outcomes of patients with hepatocellular carcinoma].

OBJECTIVE: To investigate the expression of RNA methyltransferase METTL14 in hepatocellular carcinoma (HCC) and its clinical significance. METHODS: Immunohistochemical staining was used to detect the expression of METTL14 in 147 pairs of HCC and adjacent hepatic tissues. According to the scores rated by pathologists, the 147 cases of HCC were divided into high and low METTL14 expression groups. The correlation between the expression of METTL14 and clinicopathological parameters was analyzed, and Kaplan-Meier method was used to analyze the relationship between the expression of METTL14 and the prognosis and survival (including the overall survival and disease-free survival) of the patients with HCC after operation. Univariate analysis and multivariate analysis were carried out to assess the impact of METTL14 expression level on the overall survival and tumor-free survival of the patients after operation using a COX regression model and explore whether METTL14 expression level is an independent prognostic risk factor of the postoperative patients. RESULTS: The expression of METTL14 was significantly lower in HCC tissues than in the adjacent tissues (P < 0.001). METTL14 expression in HCC tissues was significantly correlated with the tumor size (P=0.044) and TNM stage (P=0.046). A low expression of METTL14 in HCC tissues was significantly correlated with a poor prognosis and a significantly shortened overall survival time and disease-free survival time of the patients (P < 0.05), and was an independent risk factor affecting the overall survival and disease-free survival of HCC patients. CONCLUSIONS: METTL14 may be a new prognostic marker for patients with HCC after hepatectomy.

Uniform Polypyrrole Layer-Coated Sulfur/Graphene Aerogel via the Vapor-Phase Deposition Technique as the Cathode Material for Li-S Batteries.

The practical application of Li-S batteries is hampered because of their poor cycling stability caused by electrolyte-dissolved lithium polysulfides. Dual functionalities such as strong chemical adsorption stability and high conductivity are highly desired for an ideal host material for the sulfur-based cathode. Herein, a uniform polypyrrole layer-coated sulfur/graphene aerogel composite is designed and synthesized using a novel vapor-phase deposition method. The polypyrrole layer simultaneously acts as a host and an adsorbent for efficient suppression of polysulfide dissolution through strong chemical interaction. The density functional theory calculations reveal that the polypyrrole could trap lithium polysulfides through stronger bonding energy. In addition, the deflation of sulfur/graphene hydrogel during the vapor-phase deposition process enhances the contact of sulfur with matrices, resulting in high sulfur utilization and good rate capability. As a result, the synthesized polypyrrole-coated sulfur/graphene aerogel composite delivers specific discharge capacities of 1167 and 409.1 mA h g-1 at 0.2 and 5 C, respectively. Moreover, the composite can maintain a capacity of 698 mA h g-1 at 0.5 C after 500 cycles, showing an ultraslow decay rate of 0.03% per cycle.

Interfacial Engineering of Nickel Boride/Metaborate and Its Effect on High Energy Density Asymmetric Supercapacitors.

Solid materials with special atomic and electronic structures are deemed desirable platforms for establishing clear relationships between surface/interface structure characteristics and electrochemical activity. In this work, nickel boride (NixB) and nickel boride/graphene (NixB/G) are chosen as positive materials of supercapacitors. The NixB/G displays higher specific capacitance (1822 F g-1) than that of NixB (1334 F g-1) at 1 A g-1, and it still maintains 1179 F g-1 at 20 A g-1, suggesting the high rate performance. The asymmetric supercapacitor device (NixB/G//activated carbon) also delivered a very high energy density of 50.4 Wh kg-1, and the excellent electrochemical performance is ascribed to the synergistic effect of NixB, Ni(BO2)2, and graphene that fully enhances the diffusion of OH- and the electron transport. During the cycles, the prepared ultrafine NixB nanoparticles will be gradually in situ converted into ß-Ni(OH)2 which has a smaller particle size than that prepared by other methods. This will enhance the utilization of Ni(OH)2 and decrease the ion diffusion distance. The electron deficient state of B in Ni(BO2)2 amorphous shell will make it easy to accept extra electrons, enhancing the adsorption of OH- at the shell surface. Moreover, Ni(BO2)2 makes strong adhesion between NixB (or ß-Ni(OH)2) and graphene and protects the core structure in a stable state, extending the cycle life. The above properties of NixB/G endow the electrode good capacitive performance.

Association of Preoperative Hypercoagulability with Poor Prognosis in Hepatocellular Carcinoma Patients with Microvascular Invasion After Liver Resection: A Multicenter Study.

BACKGROUND: Microvascular invasion (MVI) predicts poor prognosis in patients with hepatocellular carcinoma (HCC). HCC patients with hypercoagulability are prone to develop thrombosis; however, the relationship between preoperative coagulability state, as reflected by the international normalized ratio (INR) level, and MVI remains unclear. METHODS: From January 2009 to December 2012, HCC patients who underwent R0 liver resection (LR) from four cancer centers entered into this study. The overall survival (OS) and recurrence-free survival (RFS) rates were compared using the Kaplan-Meier method and Cox regression analysis. RESULTS: Of the 2509 HCC patients who were included into this study, 1104 were found to have MVI in the resected specimens. These patients were divided into the low (n = 151), normal (n = 796), and high (n = 157) INR subgroups based on the preoperative INR levels. The low INR subgroup had a significantly higher incidence of MVI than the normal or high INR subgroups (61.6% vs. 41.6% vs. 44.6%; p < 0.001). HCC patients with MVI were significantly more likely to have a low preoperative INR level (p < 0.001); the INR level (p < 0.001) was an independent risk factor of OS and RFS. HCC patients with MVI in the low INR subgroup had significantly worse RFS and OS than the normal or high INR subgroups (median RFS 13.5 vs. 20.2 vs. 21.6 months, p < 0.001; median OS 35.5 vs. 59.5 vs. 57.0 months, p < 0.001). CONCLUSIONS: Preoperative hypercoagulability was associated with poor long-term prognosis in HCC patients with MVI after R0 LR.

Adjuvant transarterial chemoembolization improves survival outcomes in hepatocellular carcinoma with microvascular invasion: A systematic review and meta-analysis.

BACKGROUND: The benefits of adjuvant transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) remain controversial. We compared the efficacy and safety of adjuvant TACE and hepatic resection (HR) alone for HCC patients with MVI. METHODS: The PubMed, EMBASE, Cochrane Library, VIP, Wan Fang, and Sino Med databases were systematically searched to compare adjuvant TACE and HR alone for the treatment of HCC with MVI from inception to January 1, 2019. The study outcomes, including overall survival (OS) and disease-free survival (DFS), were extracted independently by two authors. RESULTS: 12 trials involving 2190 patients were evaluated. A meta-analysis of 11 studies suggested that the 1-, 3-, and 5-year overall survival (OS) rates (OR = 0.33, P < 0.001; OR = 0.49, P < 0.001; and OR = 0.59, P < 0.01; respectively), favored adjuvant TACE over HR alone. 11 studies were included in the meta-analysis of DFS, and adjuvant TACE showed better 1-, 3-, and 5-DFS (OR = 0.45, P < 0.001; OR = 0.50, P < 0.001; and OR = 0.58, P < 0.001; respectively) compared to HR alone. Subgroup analysis demonstrated that adjuvant TACE could benefit HCC patients with MVI with tumor diameter >5 cm or multinodular tumors. CONCLUSION: Adjuvant TACE may improve OS and DFS for HCC patients with MVI compared to HR alone and should be recommended for selected HCC patients with MVI. However, these results need to be validated through further high-quality clinical studies. LAY SUMMARY: The benefits of adjuvant TACE in HCC patients with microvascular invasion remain controversial. Twelve studies involving 2190 patients were include in our meta-analysis. Adjuvant TACE may improve OS and DFS for HCC patients with MVI compared to HR alone and should be recommended for selected HCC patients with MVI.

Postoperative adjuvant sorafenib improves survival outcomes in hepatocellular carcinoma patients with microvascular invasion after R0 liver resection: a propensity score matching analysis.

BACKGROUND: Microvascular invasion (MVI) is a major determinant of survival outcome for hepatocellular carcinoma (HCC). This study aimed to investigate the efficacy of postoperative adjuvant Sorafenib (PA-Sorafenib) in HCC patients with MVI after R0 liver resection (LR). METHODS: The data of patients who underwent R0 LR for HCC with histologically confirmed MVI at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. The survival outcomes for patients who underwent PA-Sorafenib were compared with those who underwent R0 LR alone. Propensity score matching (PSM) analysis was performed. RESULTS: 728 HCC patients had MVI in the resected specimens after R0 resection, with 581 who underwent LR alone and 147 patients who received in additional adjuvant sorafenib. PSM matched 113 patients in each of these two groups. The overall survival (OS) and recurrence free survival (RFS) were significantly better for patients in the PA-sorafenib group (for OS: before PSM, P = 0.003; after PSM, P = 0.007), (for RFS: before PSM, P = 0.029; after PSM, P = 0.001), respectively. Similar results were obtained in patients with BCLC 0-A, BCLC B and Child-Pugh A stages of disease. CONCLUSIONS: PA-Sorafenib was associated with significantly better survival outcomes than LR alone for HCC patients with MVI.

Long non-coding RNA DILC suppresses bladder cancer cells progression.

Accumulative researches have demonstrated the critical functions of long non-coding RNAs (lncRNAs) in the progression of malignant tumors, including bladder cancer (BC). Our previous studies showed that lnc-DILC was an important tumor suppressor gene in both liver cancer and colorectal cancer. However, the role of lnc-DILC in BC remains to be elucidated. In the present study, we for first found that lnc-DILC was downregulated in human bladder cancer tissues. Lnc-DILC overexpression suppressed the proliferation, metastasis and expansion of bladder cancer stem cells (CSCs). Mechanically, lnc-DILC suppressed BC cells progression via STAT3 pathway. Special STAT3 inhibitor S3I-201 diminished the discrepancy of growth, metastasis and self-renewal ability between lnc-DILC-overexpression BC cells and their control cells, which further confirmed that STAT3 was acquired for lnc-DILC-disrupted BC cell growth, metastasis and self-renewal. Taken together, our results suggest that lnc-DILC is a novel bladder tumor suppressor and indicate that lnc-DILC inhibits BC progression via inactivating STAT3 signaling.

Oncofetal HLF transactivates c-Jun to promote hepatocellular carcinoma development and sorafenib resistance.

BACKGROUND AND AIMS: The unique expression pattern makes oncofetal proteins ideal diagnostic biomarkers and therapeutic targets in cancer. However, few oncofetal proteins have been identified and entered clinical practice. METHODS: Fetal liver, adult liver and hepatocellular carcinoma (HCC) tissues were employed to assess the expression of hepatic leukaemia factor (HLF). The impact of HLF on HCC onset and progression was investigated both in vivo and in vitro. The association between HLF and patient prognosis was determined in patient cohorts. The correlation between HLF expression and sorafenib benefits in HCC was further evaluated in patient cohorts and patient-derived xenografts (PDXs). RESULTS: HLF is a novel oncofetal protein which is reactivated in HCC by SOX2 and OCT4. Functional studies revealed that HLF transactivates c-Jun to promote tumour initiating cell (TIC) generation and enhances TIC-like properties of hepatoma cells, thus driving HCC initiation and progression. Consistently, our clinical investigations elucidated the association between HLF and patient prognosis and unravelled the close correlation between HLF levels and c-Jun expression in patient HCCs. Importantly, HLF/c-Jun axis determines the responses of hepatoma cells to sorafenib treatment, and interference of HLF abrogated c-Jun activation and enhanced sorafenib response. Analysis of patient cohorts and PDXs further suggests that HLF/c-Jun axis might serve as a biomarker for sorafenib benefits in HCC patients. CONCLUSIONS: Our findings uncovered HLF as a novel oncofetal protein and revealed the crucial role of the HLF/c-Jun axis in HCC development and sorafenib response, rendering HLF as an optimal target for the prevention and intervention of HCC.

A nomogram to predict early postoperative recurrence of hepatocellular carcinoma with portal vein tumour thrombus after R0 liver resection: A large-scale, multicenter study.

BACKGROUND: Portal vein tumour thrombus (PVTT) is a significant poor prognostic factor for hepatocellular carcinoma (HCC). Patients with PVTT limited to a first-order branch or above of the main portal vein (MPV) could benefit from R0 liver resection (LR). A nomogram is needed to predict early postoperative recurrence (ER) in HCC patients with PVTT and to guide selection of these patients for adjuvant therapy to reduce postoperative recurrence risks. METHODS: HCC patients with PVTT limited to a first-order branch or above of the MPV after R0 LR as an initial therapy were included. A nomogram using data from a retrospective training cohort was developed with the Cox regression model. The model was tested in a prospective internal validation cohort and three external validation cohorts. RESULTS: Of 979 patients, 657 developed postoperative ER (67.1%). ER occurred in 165 of 264 patients (62.5%) in the training cohort, 146 of 218 patients (70.0%) in the internal validation cohort, and 204 of 284 patients (71.8%), 77 of 113 patients (68.1%), and 65 of 100 patients (65%) in the three external validation cohorts, respectively. The nomogram included the following variables: hepatitis B surface antigen (HBsAg), PVTT, HBV DNA, satellite nodules, α-fetoprotein, and tumour diameter. The ROC were 0.836, 0.763, 0.802, 0.837, and 0.846 in predicting ER in the five respective cohorts. CONCLUSION: A nomogram was developed and validated to predict postoperative ER in patients with HCC with PVTT after R0 LR. This nomogram could select appropriate patients with high ER risks for postoperative adjuvant therapy.