Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells

BACKGROUND Liver fibrosis is the common pathological process associated with the occurrence and development of various chronic liver diseases.At present,there is still a lack of effective prevention and treatment methods in clinical practice.Hepatic stellate cell(HSC)plays a key role in liver fibrogenesis.In recent years,the study of liver fibrosis targeting HSC autophagy has become a hot spot in this research field.Angiotensin-converting enzyme 2(ACE2)is a key negative regulator of reninangiotensin system,and its specific molecular mechanism on autophagy and liver fibrosis needs to be further explored.AIM To investigate the effect of ACE2 on hepatic fibrosis in mice by regulating HSC autophagy through the Adenosine monophosphate activates protein kinases(AMPK)/mammalian target of rapamycin(mTOR)pathway.METHODS Overexpression of ACE2 in a mouse liver fibrosis model was induced by injection of liver-specific recombinant adeno-associated virus ACE2 vector(rAAV2/8-ACE2).The degree of liver fibrosis was assessed by histopathological staining and the biomarkers in mouse serum were measured by Luminex multifactor analysis.The number of apoptotic HSCs was assessed by terminal deoxynucleoitidyl transferase-mediated dUTP nick-end labeling(TUNEL)and immunofluorescence staining.Transmission electron microscopy was used to identify the changes in the number of HSC autophagosomes.The effect of ACE2 overexpression on Wu Y et al.ACE2 improves liver fibrosis through autophagy WJG https://www.wjgnet.com 4976 September 7,2023 Volume 29 Issue 33 autophagy-related proteins was evaluated by multicolor immunofluorescence staining.The expression of autophagy-related indicators and AMPK pathway-related proteins was measured by western blotting.RESULTS A mouse model of liver fibrosis was successfully established after 8 wk of intraperitoneal injection of carbon tetrachloride(CCl4).rAAV2/8-ACE2 administration reduced collagen deposition and alleviated the degree of liver fibrosis in mice.The serum levels of platelet-derived growth factor,angiopoietin-2,vascular endothelial growth factor and angiotensin II were decreased,while the levels of interleukin(IL)-10 and angiotensin-(1-7)were increased in the rAAV2/8-ACE2 group.In addition,the expression of alpha-smooth muscle actin,fibronectin,and CD31 was down-regulated in the rAAV2/8-ACE2 group.TUNEL and immunofluorescence staining showed that rAAV2/8-ACE2 injection increased HSC apoptosis.Moreover,rAAV2/8-ACE2 injection notably decreased the number of autophagosomes and the expression of autophagy-related proteins(LC3I,LC3II,Beclin-1),and affected the expression of AMPK pathway-related proteins(AMPK,p-AMPK,p-mTOR).CONCLUSION ACE2 overexpression can inhibit HSC activation and promote cell apoptosis by regulating HSC autophagy through the AMPK/mTOR pathway,thereby alleviating liver fibrosis and hepatic sinusoidal remodeling.

Percutaneous transhepatic intraportal biopsy using gastroscope biopsy forceps for diagnosis of a pancreatic neuroendocrine neoplasm:A case report

BACKGROUND Pancreatic neuroendocrine neoplasms(PNENs)are a rare group of neoplasms originating from the islets of the Langerhans.Portal vein tumor thrombosis has been reported in 33%of patients with PNENs.While the histopathological diagnosis of PNENs is usually based on percutaneous biopsy or endoscopic ultrasound-guided fine-needle aspiration(EUS-FNA),these approaches may be impeded by gastric varices,poor access windows,or anatomically contiguous critical structures.Obtaining a pathological diagnosis using a gastroscope biopsy forceps via percutaneous transhepatic intravascular pathway is an innovative method that has rarely been reported.CASE SUMMARY A 72-year-old man was referred to our hospital for abdominal pain and melena.Abdominal contrast-enhanced magnetic resonance imaging revealed a wellenhanced tumor(size:2.4 cm×1.2 cm×1.2 cm)in the pancreatic tail with portal vein invasion.Traditional pathological diagnosis via EUS-FNA was not possible because of diffuse gastric varices.We performed a percutaneous transportal biopsy of the portal vein tumor thrombus using a gastroscope biopsy forceps.Histopathologic examination revealed a pancreatic neuroendocrine neoplasm(G2)with somatostatin receptors 2(+),allowing systemic treatment.CONCLUSION Intravascular biopsy using gastroscope biopsy forceps appears to be a safe and effective method for obtaining a histopathological diagnosis.Although welldesigned clinic trials are required to obtain more definitive evidence,this procedure may help improve the diagnosis of portal vein thrombosis and related diseases.

Molecular Characterization of Segments S7 to S10 of a Southern Rice Black-streaked Dwarf Virus Isolate from Maize in Northern China

Southern rice black-streaked dwarf virus (SRBSDV) is a novel Fijivirus prevalent in rice in southern and central China,and northern Vietnam. Its genome has 10 segments of double-stranded RNA named S1 to S10 according to their size. An isolate of SRBSDV,JNi4,was obtained from naturally infected maize plants from Ji'ning,Shandong province,in the 2008 maize season. Segments S7 to S10 of JNi4 share nucleotide identities of 72.6%-73.1%,72.3%-73%,73.9%-74.5% and 77.3%-79%,respectively,with corresponding segments of Rice black-streaked dwarf virus isolates,and identities of 99.7%,99.1%-99.7%,98.9%-99.5%,and 98.6%-99.2% with those of SRBSDV isolates HN and GD. JNi4 forms a separate branch with GD and HN in the phylogenetic trees constructed with genomic sequences of S7 to S10. These results confirm the proposed taxonomic status of SRBSDV as a distinct species of the genus Fijivirus and indicate that JNi4 is an isolate of SRBSDV. Shandong is so far the northernmost region where SRBSDV is found in China.

Comparison of modified percutaneous transhepatic variceal embolization and endoscopic cyanoacrylate injection for gastric variceal rebleeding

AIM:To compare the efficacy of modified percutaneous transhepatic variceal embolization(PTVE)with 2-octyl-cyanoacrylate(2-OCA)and endoscopic variceal obturation(EVO)with an injection of 2-OCA for prophylaxis of gastric variceal rebleeding. METHODS:In this retrospective study,the medical records of liver cirrhosis patients with gastric variceal bleeding who underwent either endoscopic 2-OCA(EVO) or modified PTVE using 2-OCA at Shandong Provincial Hospital from January 2006 to December 2008 were reviewed.Patient demographics,rebleeding rate,survival rate,and complications were compared between the two groups(PTVE and EVO).All results were expressed as mean±SD,or as a percentage.Quantitative variables were compared by two sample Student t tests, and qualitative variables were compared by the Fisher exact test or theχ 2 test(with Yates correction)where appropriate.A P value less than 0.05 was considered significant.Statistical computation was performed using SPSS 13.0 software. RESULTS:A total of 77 patients were included;45 patients who underwent EVO and 32 patients who received PTVE.During the follow-up(19.78±7.70 mo in the EVO group,vs 21.53±8.56 mo in the PTVE group) rebleeding occurred in 17 patients in the EVO group and in 4 patients in the PTVE group(37.78%vs 12.5%, P=0.028).The cumulative rebleeding-free rate was 75%,59%,and 49%in 1,2,and 3 years respectively for EVO,and 93%,84%,and 84%for PTVE(P=0.011). Cox analysis was used to identify independent factors that predicted rebleeding after treatment.Variables including age,gender,cause,Child-Pugh classification, size of gastric varices(GV),location of GV,and treatment methods were analyzed.It was revealed that Child-Pugh classification[risk ratio(RR)2.10,95%CI:1.03-4.28,P=0.040],choice of treatment(RR 0.25, 95%CI:0.08-0.80,P=0.019),and size of GV(RR 2.14, 95%CI:1.07-4.28,P=0.032)were the independent factors for predicting rebleeding.Follow-up computed tomography revealed that cyanoacrylate was retained in the varices and in the feeding veins of PTVE patients. During the follow-up,eight patients in the EVO group and four patients in the PTVE group died.The cumulative survival rates at 1,2,and 3 years were 93%,84%, and 67%respectively in the EVO group,and 97%, 88%,and 74%respectively in the PTVE group.The survival rates were not significantly different between the two groups(P=0.432).Cox analysis showed that the Child-Pugh classification was the most significant prognostic factor of survival(RR 2.77,95%CI:1.12-6.80,P=0.027).The incidence of complications was similar in both groups. CONCLUSION:With extensive and permanent obliteration of gastric varices and its feeding veins,PTVE with 2-OCA is superior to endoscopic 2-OCA injection for preventing gastric variceal rebleeding.

MDCT angiography to evaluate the therapeutic effect of PTVE for esophageal varices

Abstract AIM:To evaluate the role of multi-detector row computed tomography(MDCT) angiography for assessing the therapeutic effects of percutaneous transhepatic variceal embolization(PTVE) for esophageal varices(EVs).METHODS:The subjects of this prospective study were 156 patients who underwent PTVE with cyanoacrylate for EVs.Patients were divided into three groups according to the filling range of cyanoacrylate in EVs and their feeding vessels:(1) group A,complete obliteration,with at least 3 cm of the lower EVs and peri-/EVs,as well as the adventitial plexus of the gastric cardia and fundus filled with cyanoacrylate;(2) group B,partial obliteration of varices surrounding the gastric cardia and fundus,with their feeding vessels being obliterated with cyanoacrylate,but without reaching lower EVs;and(3) group C,trunk obliteration,with the main branch of the left gastric vein being filled with cyanoacrylate,but without reaching varices surrounding the gastric cardia or fundus.We performed chart reviews and a prospective follow-up using MDCT images,angiography,and gastrointestinal endoscopy.RESULTS:The median follow-up period was 34 mo.The rate of eradication of varices for all patients was 56.4%(88/156) and the rate of relapse was 31.3%(41/131).The rates of variceal eradication at 1,3,and 5 years after PTVE were 90.2%,84.1% and 81.7%,respectively,for the complete group;61.2%,49% and 42.9%,respectively,for the partial group;with no varices disappearing in the trunk group.The relapsefree rates at 1,3 and 5 years after PTVE were 91.5%,86.6% and 81.7%,respectively,for the complete group;71.1%,55.6% and 51.1%,respectively,for the partial group;and all EVs recurred in the trunk group.Kaplan-Meier analysis showed P values of 0.000 and 0.000,and odds ratios of 3.824 and 3.603 for the rates of variceal eradication and relapse free rates,respectively.Cyanoacrylate in EVs disappeared with time,but those in the EVs and other feeding vessels remained permanently in the vessels without a decrease with time,which is important for the continued obliteration of the feeding vessels and prevention of EV relapse.CONCLUSION:MDCT provides excellent visualization of cyanoacrylate obliteration in EV and their feeding veins after PTVE.It confirms that PTVE is effective for treating EVs.

Risk factors for early rebleeding and mortality in acute variceal hemorrhage

AIM:To investigate the risk factors for 6-wk rebleeding and mortality in acute variceal hemorrhage(AVH)patients treated by percutaneous transhepatic variceal embolization(PTVE).METHODS:A retrospective cohort study of AVH patients who had undergone PTVE treatment was conducted between January 2010 and December 2012.Demographic information,medical histories,physical examination findings,and laboratory test results were collected.The PTVE procedure was performed as a rescue therapy for patients who failed endoscopic and pharmacologic treatment.Survival analysis was estimated using the Kaplan-Meier method and compared using the log-rank test.The multivariate analysis was performed using the Cox regression test to identify independent risk factors for rebleeding and mortality.RESULTS:One hundred and one patients were included;71 were males and the average age was 51 years.Twenty-one patients rebled within 6 wk.Patients with high-risk stigmata,PTVE with trunk obliteration,and a hepatic vein pressure gradient(HVPG)≥20 mm Hg were at increased risk for rebleeding(OR=5.279,95%CI:2.782-38.454,P=0.003;OR=4.309,95%CI:=2.144-11.793,P<0.001;and OR=1.534,95%CI:1.062-2.216,P=0.022,respectively).Thirteen patients died within 6 wk.A model for end-stage liver disease(MELD)score≥18 and an HVPG≥20 mm Hg were associated with 6-wk mortality(OR=2.162,95%CI:1.145-4.084,P=0.017 and OR=1.423,95%CI:1.222-1.657,P<0.001,respectively).CONCLUSION:MELD score and HVPG in combination allow for early identification of patients with AVH who are at substantially increased risk of death over the short term.

Metformin attenuates motility,contraction,and fibrogenic response of hepatic stellate cells in vivo and in vitro by activating AMP-activated protein kinase

AIM To investigate the effect of metformin on activated hepatic stellate cells(HSCs) and the possible signaling pathways involved. METHODS A fibrotic mouse model was generated by intraperitoneal injection of carbon tetrachloride(CCl_4) and subsequent treatment with or without metformin. The level of fibrosis was detected by hematoxylin-eosin staining, Sirius Red staining, and immunohistochemistry. The HSC cell line LX-2 was used for in vitro studies. The effect of metformin on cell proliferation(CCK8 assay),motility(scratch test and Transwell assay), contraction(collagen gel contraction assay), extracellular matrix(ECM) secretion(Western blot), and angiogenesis(ELISA and tube formation assay) was investigated. We also analyzed the possible signaling pathways involved by Western blot analysis.RESULTS Mice developed marked liver fibrosis after intraperitoneal injection with CCl_4 for 6 wk. Metformin decreased the activation of HSCs, reduced the deposition of ECM, and inhibited angiogenesis in CCl_4-treated mice. Platelet-derived growth factor(PDGF) promoted the fibrogenic response of HSCs in vitro, while metformin inhibited the activation, proliferation, migration, and contraction of HSCs, and reduced the secretion of ECM. Metformin decreased the expression of vascular endothelial growth factor(VEGF) in HSCs through inhibition of hypoxia inducible factor(HIF)-1α in both PDGF-BB treatment and hypoxic conditions, and it down-regulated VEGF secretion by HSCs and inhibited HSC-based angiogenesis in hypoxic conditions in vitro. The inhibitory effects of metformin on activated HSCs were mediated by inhibiting the Akt/mammalian target of rapamycin(m TOR) and extracellular signal-regulated kinase(ERK) pathways via the activation of adenosine monophosphate-activated protein kinase(AMPK).CONCLUSION Metformin attenuates the fibrogenic response of HSCs in vivo and in vitro, and may therefore be useful for the treatment of chronic liver diseases.

Carvedilol may attenuate liver cirrhosis by inhibiting angiogenesis through the VEGF-Src-ERK signaling pathway

AIM: To investigate the effect of carvedilol on angiogenesis and the underlying signaling pathways.METHODS: The effect of carvedilol on angiogenesis was examined using a human umbilical vascular endothelial cell(HUVEC) model. The effect of carvedilol on cell viability was measured by CCK8 assay. Flow cytometry was used to assess the effect of carvedilol on cell cycle progression. Cell migration, transwell migration and tube formation assays were performed to analyze the effect of carvedilol on HUVEC function. Vascular endothelial growth factor(VEGF) induced activation of HUVECs, which were pretreated with different carvedilol concentrations or none. Western blot analysis detected the phosphorylation levels of three cell signaling pathway proteins, VEGFR-2, Src, and extracellular signal-regulated kinase(ERK). The specific Src inhibitor PP2 was used to assess the role of Src in the VEGF-induced angiogenic pathway.RESULTS: Carvedilol inhibited HUVEC proliferation in a dose-dependent manner(IC50 = 38.5 mmol/L). The distribution of cells in the S phase decreased from 43.6% to 37.2%, 35.6% and 17.8% by 1, 5 and 10 μmol/L carvedilol for 24 h, respectively. Carvedilol(10 μmol/L) reduced VEGF-induced HUVEC migration from 67.54 ± 7.83 to 37.11 ± 3.533(P < 0.001). Carvedilol concentrations of 5 μmol/L and 10 μmol/L reduced cell invasion from 196.3% ± 18.76% to 114.0% ± 12.20% and 51.68% ± 8.28%, respectively. VEGFinduced tube formation was also reduced significantly by 5 μmol/L and 10 μmol/L carvedilol from 286.0 ± 36.72 to 135.7 ± 18.13(P < 0.05) and 80.27 ± 11.16(P < 0.01) respectively. We investigated several intracellular protein levels to determine the reason for these reductions. Treatment with 10 μmol/L carvedilol reduced VEGF-induced tyrosine phosphorylation of VEGFR-2 from 175.5% ± 8.54% to 52.67% ± 5.33%(P < 0.01). Additionally, 10 μmol/L carvedilol reduced VEGF-induced ERK 1/2 phosphorylation from 181.9% ± 18.61% to 56.45% ± 7.64%(P < 0.01). The VEGFinduced increase in Src kinase activity was alleviated by carvedilol [decreased from 141.8% ± 15.37% to 53.57 ± 7.18%(P < 0.01) and 47.04% ± 9.74%(P < 0.01) at concentrations of 5 and 10 μmol/L, respectively]. Pretreatment of HUVECs with Src kinase inhibitor almost completely prevented the VEGF-induced ERK upregulation [decreased from 213.2% ± 27.68% to 90.96% ± 17.16%(P < 0.01)].CONCLUSION: Carvedilol has an anti-angiogenic effect on HUVECs. This inhibitory effect is mediated by VEGF-induced Src-ERK signaling pathways.

Transjugular intrahepatic portosystemic shunt for the prevention of recurrent esophageal variceal bleeding in patients with cavernous transformation of portal vein

Background: Treatment options for patients with cavernous transformation of portal vein(CTPV) are limited. This study aimed to evaluate the feasibility, efficacy and safety of transjugular intrahepatic portosystemic shunt(TIPS) to prevent recurrent esophageal variceal bleeding in patients with CTPV. Methods: We retrospectively analyzed 67 consecutive patients undergone TIPS from January 2011 to December 2016. All patients were diagnosed with CTPV. The indication for TIPS was a previous episode of variceal bleeding. The data on recurrent bleeding, stent patency, hepatic encephalopathy and survival were retrieved and analyzed. Results: TIPS procedure was successfully performed in 56 out of 67(83.6%) patients with CTPV. TIPS was performed via a transjugular approach alone( n = 15), a combined transjugular/transhepatic approach( n = 33) and a combined transjugular/transsplenic approach( n = 8). Mean portosystemic pressure gradient(PSG) decreased from 28.09 ± 7.28 mmHg to 17.53 ± 6.12 mmHg after TIPS( P < 0.01). The probability of the remaining free recurrent variceal bleeding was 87.0%. The probability of TIPS patency reached 81.5%. Hepatic encephalopathy occurrence was 27.8%, and survival rate was 88.9% until the end of follow-up. Four out of 11 patients who failed TIPS died, and 4 had recurrent bleeding. Conclusions: TIPS should be considered a safe and feasible alternative therapy to prevent recurrent esophageal variceal bleeding in patients with CTPV, and to achieve clinical improvement.

Transjugular intrahepatic portosystemic shunt is effective in patients with chronic portal vein thrombosis and variceal bleeding

Background:Studies about treatment of patients with chronic portal vein thrombosis(CPVT)are still limited,especially in different types of CPVT.This study aimed to evaluate the effect of transjugular intrahepatic portosystemic shunt(TIPS)in all types of CPVT with variceal bleeding.Methods:Patients with CPVT who received TIPS treatment between January 2011 and June 2019 were divided into four types according to the extent of thrombosis.All patients had a history of variceal bleeding.The characteristics and clinical parameters were collected and recorded.Data on procedure success rate,variation in portal vein pressure,rebleeding,hepatic encephalopathy(HE),stent stenosis,and overall mortality were analyzed.Results:A total of 189 patients were included in this study(39 in type 1,84 in type 2,48 in type 3,18 in type 4).The TIPS procedure success rate was 86.2%.The success rate was significantly different among the four types(89.7%vs.88.1%vs.83.3%vs.77.8%,P=0.001).In the TIPS success group,portal vein pressure was significantly reduced from 27.15±6.59 to 19.74±6.73 mm Hg after the procedure(P<0.001)and the rebleeding rate was significantly lower than that of the fail group(14.7%vs.30.8%,P=0.017).In addition,there were no significant differences in HE rate(30.7%vs.26.9%,P=0.912)or overall mortality(12.9%vs.19.2%,P=0.403)between the TIPS success group and the fail group.In the TIPS success group,we found that the occurrence of HE was significantly different(P=0.020)among the four types,while there were no significant differences in rebleeding rate(P=0.669),stent stenosis rate(P=0.056),or overall mortality(P=0.690).Conclusions:TIPS was safe and effective in decreasing portal vein pressure and rebleeding rate in patients with CPVT.

Chinese-translated Behavioral Regulation in Exercise Questionnaire-2： Evidence from university students in the Mainland and Hong Kong of China

目的:本研究的目的是在中国大陆和中国香港的大学生人群中,进一步检验中译版《锻炼行为调节问卷-2》(C-BREQ-2)的相关心理测量学属性。方法:来自中国大陆(n=191)和中国香港(n=194)的大学生参加了本次研究,检验了C-BREQ-2的因素效度、区别效度、法则效度、内部一致性信度以及测量恒等性。结果:验证性因素分析结果为18条目C-BREQ-2的5因素结构提供了支持。因素间相关程度的95%置信区间检验表明,C-BREQ-2各因素间虽具有相关性但属不同概念,这为区分效度提供了支持。C-BREQ-2的内部一致性信度达到可接受水平。不同行为调节因素间相关系数呈简单相关模式,为C-BREQ-2的法则效度提供了支持。不同行为调节变量与情感及行为变量间的相关结果符合理论假设,进一步对其法则效度提供了支持。多组验证性因素分析结果表明,在中国大陆和中国香港大学生中,C-BREQ-2测量模型的因子载荷和因子方差/协方差具有跨人群恒等性。结论:本研究为在中国大学生人群使用C-BREQ-2进一步提供了心理测量学证据,也使得以自我决定理论为基础的相关动机理论在中国人人群以及在锻炼和体力活动等领域的进一步研究与应用成为可能。

Assessing acceptance in mindfulness with direct-worded items:The development and initial validation of the Athlete Mindfulness Questionnaire

Purpose:The purpose of the current study was to develop and validate a sport-specific mindfulness measure,the Athlete Mindfulness Questionnaire(AMQ),through 5 related studies using 4 separate samples of Chinese athletes.The AMQ is a 3-factor measure designed to assess mindfulness that reflects present-moment attention,awareness,and acceptance in a sport context.Methods:In Study 1,an initial pool of items was generated based on previous literature,existing mindfulness scales,as well as interviews with and feedback from the athletes,coaches,and mindfulness experts.Initial support for the 3-factor structure of the AMQ was established via exploratory factor analysis in Study 2,and cross-validated through confirmatory factor analysis in Studies 3 and 4.In Study 5,a modified 3-factor AMQ with direct-worded acceptance items was examined in a fourth independent sample.Results:Convergent and concurrent validities of the acceptance subscale failed to be established in Studies 3 and 4 which may be due to the inattention and confusion of the athletes whilst interpreting the reverse-worded items.A modified 16-item AMQ in Study 5 displayed satisfactory model fit and acceptable internal consistencies.Most importantly,convergent and concurrent validities of the 16-item AMQ were supported.The3 subscales showed significant positive associations with mindfulness,flow,well-being,and positive affect and significant negative associations with experiential avoidance,burnout,and negative affect.Conclusion:The AMQ is a psychometrically sound measure of mindfulness in a sport context.The importance of using direct-worded acceptance items is discussed.

Validation and evaluation of clinical prediction systems for first and repeated transarterial chemoembolization in unresectable hepatocellular carcinoma: A Chinese multicenter retrospective study

BACKGROUND The treatment outcome of transarterial chemoembolization(TACE)in unresectable hepatocellular carcinoma(HCC)varies greatly due to the clinical heterogeneity of the patients.Therefore,several prognostic systems have been proposed for risk stratification and candidate identification for first TACE and repeated TACE(re-TACE).AIM To investigate the correlations between prognostic systems and radiological response,compare the predictive abilities,and integrate them in sequence for outcome prediction.METHODS This nationwide multicenter retrospective cohort consisted of 1107 unresectable HCC patients in 15 Chinese tertiary hospitals from January 2010 to May 2016.The Hepatoma Arterial-embolization Prognostic(HAP)score system and its modified versions(mHAP,mHAP2 and mHAP3),as well as the six-and-twelve criteria were compared in terms of their correlations with radiological response and overall survival(OS)prediction for first TACE.The same analyses were conducted in 912 patients receiving re-TACE to evaluate the ART(assessment for re-treatment with TACE)and ABCR(alpha-fetoprotein,Barcelona Clinic Liver Cancer,Child-Pugh and Response)systems for post re-TACE survival(PRTS).RESULTS All the prognostic systems were correlated with radiological response achieved by first TACE,and the six-and-twelve criteria exhibited the highest correlation(Spearman R=0.39,P=0.026)and consistency(Kappa=0.14,P=0.019),with optimal performance by area under the receiver operating characteristic curve of 0.71[95%confidence interval(CI):0.68-0.74].With regard to the prediction of OS,the mHAP3 system identified patients with a favorable outcome with the highest concordance(C)-index of 0.60(95%CI:0.57-0.62)and the best area under the receiver operating characteristic curve at any time point during follow-up;whereas,PRTS was well-predicted by the ABCR system with a C-index of 0.61(95%CI:0.59-0.63),rather than ART.Finally,combining the mHAP3 and ABCR systems identified candidates suitable for TACE with an improved median PRTS of 36.6 mo,compared with non-candidates with a median PRTS of 20.0 mo(logrank test P<0.001).CONCLUSION Radiological response to TACE is closely associated with tumor burden,but superior prognostic prediction could be achieved with the combination of mHAP3 and ABCR in patients with unresectable liver-confined HCC.

Synthesis and Properties of SEPS-g-PEO Copolymers with Varying Branch Lengths

Poly（ethylene oxide） （PEO） was controllably grafted from styrene-b-（ethylene-co-propylene）-b-styrene （SEPS） backbones by combining lithiation of styrenic units and living monomer-activated anionic ring-opening polymerization of ethylene oxide （EO） monomers with the aid of co-initiators triisobutyl aluminum. The as-synthesized SEPS-g-PEO copolymers were characterized by SEC, 1H-NMR, FTIR, SAXS, AFM and DSC. When the branch length is relatively small, increase of PEO fraction leads to the increase of the correlation length between neighboring hard domains, but the degree of correlation reduces. When the branch length is relatively large, the phase-separated structures become random both in terms of size and spatial correlation, and macro-phase separated structures appear. The crystallization behavior of the PEO branches can be effectively inhibited in SEPS-g-PEO, so no significant crystallization takes place until the fraction of PEO branches is 20.1 wt%, which greatly promotes the rapid delivery of hydrophilic drugs in the hot-melting pressure- sensitive adhesives （HMPSAs） based on SEPS-g-PEO. Their cumulative release amount of a model drug could achieve 80%, more than twice the value in the HMPSAs based on linear PEO-containing styrenic block copolymers.