Deep-learning-assisted inverse design of dual-spin/frequency metasurface for quad-channel off-axis vortices multiplexing

Recently,the metasurfaces for independently controlling the wavefront and amplitude of two orthogonal circularly polarized electromagnetic(EM)waves have been demonstrated to open a way toward spin-multiplexing compact metadevices.However,these metasurfaces are mostly restricted to a single operation frequency band.The main challenge to achieving multiple frequency manipulations stems from the complicated and time-consuming design caused by multifrequency cross talk.To solve this problem,we propose a deep-learning-assisted inverse design method for designing a dual-spin/frequency metasurface with flexible multiplexing of off-axis vortices.By analyzing the cross talk between different spin/frequency channels based on the deep-learning method,we established the internal mapping relationship between the physical parameters of a meta-atom and its phase responses in multichannels,realizing the rapid inverse design of the spin/frequency multiplexing EM device.As a proof of concept,we demonstrated in the microwave region a dual-frequency arbitrary spin-to-orbit angular momentum converter,a dual-frequency off-axis vector vortex multiplexer,and a large-capacity(16-channel)vortex beam generator.The proposed method may provide a compact and efficient platform for the multiplexing of vortices,which may further stimulate their applications in wireless communication and quantum information science.

广义论证理论的语用学基础——从顺应论观点看

广义论证理论框架下论证被视作藉由语言实施的社会互动,是一种通过使用自然语言进行的推理活动。其独特的研究视角以及特殊的分析方法要求,在对论证进行语用分析时采取综合的视角。通过采取耶夫·维索尔伦的语言–语境“顺应”观点,本文阐释了广义论证的语用过程及该理论的语用学基础。

FoxM1 overexpression promotes epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma

AIM: To investigate the expression of forkhead box protein M1(Fox M1) in the process of epithelial mesenchymal transition in hepatocellular carcinoma(HCC) and its role in metastasis.METHODS: Fox M1 and E-cadherin expression in HCC tissue microarray specimens was evaluated by immunohistochemical staining,and statistical methods were applied to analyze the correlation between FoxM 1 and epithelial-mesenchymal transition(EMT).KaplanMeier analysis of the correlation between the Fox M1 expression level and recurrence or overall survival of HCC patients was performed.The expression of FoxM 1,E-cadherin and snail homologue 1(SNAI1) in HCC cell lines was evaluated by real-time reverse transcriptionpolymerase chain reaction and Western blot.Hepatocyte growth factor(HGF) was used to induce EMT and stimulate cell migration in HCC cells.The expression of Fox M1 and SNAI1 was regulated by transfection with plasmids pc DNA3.1 and si RNAs in vitro.The occurrence of EMT was evaluated by Transwell assay,morphologic analysis and detection of the expression of EMT markers(E-cadherin and vimentin).Luciferase and chromatin immunoprecipitation assays were used to evaluate whether SNAI1 is a direct transcriptional target of FoxM 1.RESULTS: FoxM 1 expression was increased significantly in HCC compared with para-carcinoma(10.7 ± 0.9 vs 8.2 ± 0.7,P < 0.05) and normal hepatic(10.7 ± 0.9 vs 2.7 ± 0.4,P < 0.05) tissues.Overexpression of Fox M1 was correlated with HCC tumor size,tumor number,macrovascular invasion and higher TNM stage,but was negatively correlated with E-cadherin expression in microarray specimens and in cell lines.Fox M1 overexpression was correlated significantly with HCC metastasis and EMT.In vitro,we found that FoxM 1 plays a key role in HGF-induced EMT,and overexpression of Fox M1 could suppress E-cadherin expression and induce EMT changes,which were associated with increased HCC cell invasiveness.Next,we confirmed that FOXM1 directly binds to and activates the SNAI1 promoter,and we identified SNAI1 as a direct transcriptional target of FOXM1.Moreover,inhibiting the expression of SNAI1 significantly inhibited FoxM 1-mediated EMT.CONCLUSION: Fox M1 overexpression promotes EMT and metastasis of HCC,and SNAI1 plays a critical role in FoxM 1-mediated EMT.

Central obesity and nonalcoholic fatty liver disease risk after adjusting for body mass index

AIM:To investigate whether central obesity is associated with nonalcoholic fatty liver disease(NAFLD) formation after adjusting for general obesity.METHODS:The online databases Pub Med,EMBASE,and ISI Web of Science were searched for studies estimating the influence of central obesity on NAFLD occurrence published through April 2014.Studies that did not adjust for body mass index(BMI) were excluded.In addition,the independent effect of BMI was also assessed with the included studies.The pooled effect sizes and 95% confidence intervals(CIs) were calculated using random- or fixed-effects models based on the degree of heterogeneity.Furthermore,subgroup analyses,meta-regression,sensitivity analyses,and publication bias were performed.RESULTS:Twenty eligible studies were identified.The summary odds ratio(OR) values per-unit increase in waist circumference(WC) and BMI for NAFLD formation were 1.07(95%CI:1.03-1.10,I2 = 73.9%,n = 11 studies) and 1.25(95%CI:1.13-1.38,I2 = 88.7%,n = 11 studies),respectively.When the indices were expressed as binary variables(with the non-obesity group as reference),the pooled OR in WC,waist-tohip ratio,and BMI were 2.34(95%CI:1.83-3.00,I2 = 41.8%,n = 7 studies),4.06(95%CI:1.53-10.79,I2 = 65.7%,n = 3 studies),and 2.85(95%CI:1.60-5.08,I2 = 57.8%,n = 5 studies),respectively.Using the same studies as the latter(n = 5),pooled OR in WC was 3.14(95%CI:2.07-4.77),which is greater than that in BMI.CONCLUSION:Central obesity may pose a greater threat to national health than general obesity,although both are independently associated with increased risk of NAFLD.

Six-long non-coding RNA signature predicts recurrence-free survival in hepatocellular carcinoma

BACKGROUND Recent evidence shows that long non-coding RNAs(lncRNAs) are closely related to hepatogenesis and a few aggressive features of hepatocellular carcinoma(HCC). Increasing studies demonstrate that lncRNAs are potential prognostic factors for HCC. Moreover, several studies reported the combination of lncRNAs for predicting the overall survival(OS) of HCC, but the results varied. Thus,more effort including more accurate statistical approaches is needed for exploring the prognostic value of lncRNAs in HCC.AIM To develop a robust lncRNA signature associated with HCC recurrence to improve prognosis prediction of HCC.METHODS Univariate COX regression analysis was performed to screen the lncRNAs significantly associated with recurrence-free survival(RFS) of HCC in GSE76427 for the least absolute shrinkage and selection operator(LASSO) modelling. The established lncRNA signature was validated and developed in The Cancer Genome Atlas(TCGA) series using Kaplan-Meier curves. The expression values of the identified lncRNAs were compared between the tumor and non-tumor tissues. Pathway enrichment of these lncRNAs was conducted based on the significantly co-expressed genes. A prognostic nomogram combining the lncRNA signature and clinical characteristics was constructed.RESULTS The lncRNA signature consisted of six lncRNAs: MSC-AS1, POLR2 J4, EIF3 J-AS1,SERHL, RMST, and PVT1. This risk model was significantly associated with the RFS of HCC in the TCGA cohort with a hazard ratio(HR) being 1.807(95%CI[confidence interval]: 1.329-2.457) and log-rank P-value being less than 0.001. The best candidates of the six-lncRNA signature were younger male patients with HBV infection in relatively early tumor-stage and better physical condition but with higher preoperative alpha-fetoprotein. All the lncRNAs were significantly upregulated in tumor samples compared to non-tumor samples(P < 0.05). The most significantly enriched pathways of the lncRNAs were TGF-β signaling pathway, cellular apoptosis-associated pathways, etc. The nomogram showed great utility of the lncRNA signature in HCC recurrence risk stratification.CONCLUSION We have constructed a six-lncRNA signature for prognosis prediction of HCC.This risk model provides new clinical evidence for the accurate diagnosis and targeted treatment of HCC.

Platelet to lymphocyte ratio as a novel prognostic tool for gallbladder carcinoma

AIM:To preliminarily investigate the prognostic significance of the platelet to lymphocyte ratio(PLR) in patients with gallbladder carcinoma(GBC).METHODS:Clinical data of 316 surgical GBC patients were analyzed retrospectively,and preoperative serum platelet and lymphocyte counts were used to calculate the PLR.The optimal cut-off value of the PLR for detecting death was determined by the receiver operating characteristic(ROC) curve.The primary outcome was overall survival,which was estimated by the Kaplan-Meier method.The log-rank test was used to compare the differences in survival.Then,we conducted multivariate Cox analysis to assess the independent effect of the PLR on the survival of GBC patients.RESULTS:For the PLR,the area under the ROC curve was 0.620(95%CI:0.542-0.698,P = 0.040) in detecting death.The cut-off value for the PLR was determined to be 117.7,with 73.6% sensitivity and 53.2% specificity.The PLR was found to be significantlypositively correlated with CA125 serum level,tumornode-metastasis(TNM) stage,and tumor differentiation.Univariate analysis identified carcinoembryonic antigen(CEA),CA125 and CA199 levels,PLR,TNM stage,and the degree of differentiation as significant prognostic factors for GBC when they were expressed as binary data.Multivariate analysis showed that CA125 > 35 U/mL,CA199 > 39 U/mL,PLR ≥ 117.7,and TNM stage Ⅳ were independently associated with poor survival in GBC.When expressed as a continuous variable,the PLR was still an independent predictor for survival,with a hazard ratio of 1.018(95%CI:1.001-1.037 per 10-unit increase,P = 0.043).CONCLUSION:The PLR could be used as a simple,inexpensive,and valuable tool for predicting the prognosis of GBC patients.

Hydrogen-rich water protects against inflammatory bowel disease in mice by inhibiting endoplasmic reticulum stress and promoting heme oxygenase-1 expression

AIM To investigate the therapeutic effect of hydrogen-rich water(HRW) on inflammatory bowel disease(IBD) and to explore the potential mechanisms involved.METHODS Male mice were randomly divided into the following four groups: control group, in which the mice received equivalent volumes of normal saline(NS) intraperitoneally(ip); dextran sulfate sodium(DSS) group, in which the mice received NS ip(5 m L/kg body weight, twice per day at 8 am and 5 pm) for 7 consecutive days after IBD modeling; DSS + HRW group, in which the mice received HRW(in the same volume as the NS treatment) for 7 consecutive days after IBD modeling; and DSS + HRW + Zn PP group, in which the mice received HRW(in the same volume as the NS treatment) and ZnP P [a heme oxygenase-1(HO-1) inhibitor, 25 mg/kg] for 7 consecutive days after IBD modeling. IBD was induced by feeding DSS to the mice, and blood and colon tissues were collected on the 7th d after IBD modeling to determine clinical symptoms, colonic inflammation and the potential mechanisms involved.RESULTS The DSS + HRW group exhibited significantly attenuated weight loss and a lower extent of disease activity index compared with the DSS group on the 7th d(P < 0.05). HRW exerted protective effects against colon shortening and colonic wall thickening in contrast to the DSS group(P < 0.05). The histological study demonstrated milder inflammation in the DSS + HRW group, which was similar to normal inflammatory levels, and the macroscopic and microcosmic damage scores were lower in this group than in the DSS group(P < 0.05). The oxidative stress parameters, including MDA and MPO in the colon, were significantly decreased in the DSS + HRW group compared with the DSS group(P < 0.05). Simultaneously, the protective indicators, superoxide dismutase and glutathione, were markedly increased with the use of HRW. Inflammatory factors were assessed, and the results showed that the DSS + HRW group exhibited significantly reduced levels of TNF-α, IL-6 and IL-1β compared with the DSS group(P < 0.05). In addition, the pivotal proteins involved in endoplasmic reticulum(ER) stress, including p-e IF2α, ATF4, XBP1 s and CHOP, were dramatically reduced after HRW treatment in contrast to the control group(P < 0.05). Furthermore, HRW treatment markedly up-regulated HO-1 expression, and the use of Zn PP obviously reversed the protective role of HRW. In the DSS + HRW + ZnP P group, colon shortening and colonic wall thickening were significantly aggravated, and the macroscopic damage scores were similar to those of the DSS + HRW group(P < 0.05). The histological study also showed more serious colonic damage that was similar to the DSS group.CONCLUSION HRW has a significant therapeutic potential in IBD by inhibiting inflammatory factors, oxidative stress and ER stress and by up-regulating HO-1 expression.

Seven-senescence-associated gene signature predicts overall survival for Asian patients with hepatocellular carcinoma

BACKGROUND Cellular senescence is a recognized barrier for progression of chronic liver diseases to hepatocellular carcinoma(HCC). The expression of a cluster of genes is altered in response to environmental factors during senescence. However, it is questionable whether these genes could serve as biomarkers for HCC patients.AIM To develop a signature of senescence-associated genes(SAGs) that predicts patients' overall survival(OS) to improve prognosis prediction of HCC.METHODS SAGs were identified using two senescent cell models. Univariate COX regression analysis was performed to screen the candidate genes significantly associated with OS of HCC in a discovery cohort(GSE14520) for the least absolute shrinkage and selection operator modelling. Prognostic value of this seven-gene signature was evaluated using two independent cohorts retrieved from the GEO(GSE14520) and the Cancer Genome Atlas datasets, respectively.Time-dependent receiver operating characteristic(ROC) curve analysis was conducted to compare the predictive accuracy of the seven-SAG signature and serum α-fetoprotein(AFP).RESULTS A total of 42 SAGs were screened and seven of them, including KIF18 B, CEP55,CIT, MCM7, CDC45, EZH2, and MCM5, were used to construct a prognostic formula. All seven genes were significantly downregulated in senescent cells andupregulated in HCC tissues. Survival analysis indicated that our seven-SAG signature was strongly associated with OS, especially in Asian populations, both in discovery and validation cohorts. Moreover, time-dependent ROC curve analysis suggested the seven-gene signature had a better predictive accuracy than serum AFP in predicting HCC patients' 1-, 3-, and 5-year OS.CONCLUSION We developed a seven-SAG signature, which could predict OS of Asian HCC patients. This risk model provides new clinical evidence for the accurate diagnosis and targeted treatment of HCC.

Model based on γ-glutamyltransferase and alkaline phosphatase for hepatocellular carcinoma prognosis

AIM: To determine the prognostic value of alkaline phosphatase (ALP) and &#x003b3;-glutamyltransferase (GGT) for hepatocellular carcinoma (HCC) .

Symptomatic multinodular splenic hamartoma preoperatively suspected as metastatic tumor:A case report

Splenic hamartoma(SH)is a rare benign tumor usually detected accidentally,which is composed of an aberrant mixture of normal splenic elements.Here,we report a case of 54-year-old man who presented with symptomatic multinodular SH and was admitted initially for thrombocytopenia and anemia.Physical examination revealed that the patients had an anemic appearance and palpable spleen,extending 10 cm below the costal margin.Preoperative ultrasound and computed tomography(CT)indicated splenomegaly with multinodular lesions.On enhanced CT scanning,during the arterial phase,the lesions demonstrated inhomogeneous enhancement,and in the portal phase the lesions were more hyperdense than the splenic parenchyma.The images were highly suggestive of a metastatic tumor.Splenectomy was performed 1 wk later.The tumor was eventually diagnosed as SH according to the morphological features and immunohistochemical detection,by which CD34 was positive in lining cells and some spindle cells,vimentin was positive in the tumor,factor-Ⅷ-related antigen was positive multifocally in lining cells,and smooth muscle actin was positive in some spindle cells.Thrombocytopenia and anemia were cured after splenectomy.

Down-regulation of FoxM1 inhibits viability and invasion of gallbladder carcinoma cells, partially dependent on inducement of cellular senescence

AIM: To investigate the effect of knockdown of Forkhead box M1 (FoxM1) on the proliferation and invasion capacities of human gallbladder carcinoma (GBC)-SD cells.

Significance of platelet count and platelet-based models for hepatocellular carcinoma recurrence

AIM:To explore the effects of platelet count(PLT)and11 platelet-based indices on postoperative recurrence of hepatocellular carcinoma(HCC).METHODS:We retrospectively analyzed 172 HCC patients who were treated by partial hepatectomy.Preoperative data,including laboratory biochemical results,were used to calculate the 11 indices included in the analysis.We performed receiver operating characteristic curve analysis to determine the optimal cut-off values for predicting recurrence.Cumulative rates of HCC recurrence were calculated using KaplanMeier survival curves and differences were analyzed by log-rank tests.Multivariate analyses were performed to identify independent predictors of recurrence,early recurrence(within one year after surgery),and late recurrence in HCC.To obtain better prognostic models,PLT-based indices were analyzed separately after being expressed as binary and continuous variables.Two platelet-unrelated,validated HCC prognostic models were included in the analyses as reference indices.Additional analyses were performed after patients were stratified based on hepatitis B virus infection status,cirrhosis,and tumor size to investigate the significance of platelets in different subgroups.RESULTS:In the study cohort,44.2%(76/172)of patients experienced HCC recurrence,and 50.6%(87/172)died during a median follow-up time of 46mo.PLT and five of the 11 platelet-related models were significant predisposing factors for recurrence(P<0.05).Multivariate analysis indicated that,among the clinical parameters,presence of ascites,PLT≥148×109/L,alkaline phosphatase≥116 U/L,and tumor size≥5 cm were independently associated with ahigher risk of HCC recurrence(P<0.05).Independent and significant models included the aspartate aminotransferase/PLT index,fibrosis index based on the four factors,fibro-quotient,aspartate aminotransferase/PLT/γ-glutamyl transpeptidase/alpha-fetoprotein index,and the PLT/age/alkaline phosphatase/alphafetoprotein/aspartate aminotransferase index.There were different risk factors between early and late recurrences,and PLT and these indices were more inclined to influence late recurrence.PLT was only predictive of recurrence in non-cirrhotic HCC patients,and was not influenced by tumor size,which was a critical confounder in our study.CONCLUSION:PLT and PLT-basednoninvasive models are effective tools for predicting postoperative recurrence,especially late recurrence.Larger cohorts are needed to validate our findings.

Thrombocytopenia for prediction of hepatocellular carcinoma recurrence: Systematic review and meta-analysis

AIM: To investigate the association between thrombocytopenia and relapse after treatment for hepatocellular carcinoma(HCC).METHODS: We searched the Pub Med, EMBASE, and Web of Science databases to obtain eligible studies. The hazard ratios(HRs) values and 95% confidence intervals(CIs) were pooled by random effects model. Subsequently, we estimated the heterogeneity, performed a sensitivity analysis, determined the publication bias, and performed subgroup and meta-regression analyses. Study quality was assessed by using the Oxford Center for Evidence Based Medicine tool.RESULTS: We identified 18 eligible studies by retrieval(published during 2000-2014). Out of the 4163 patients with HCC who were recruited, 2746(66.0%) experienced recurrence. In general, our meta-analysis suggested that low platelet count(PLT) before therapy significantly increased the probability of postoperative recurrence(HR = 1.53, 95%CI: 1.29-1.81). PLT was also valuable in the prediction of intrahepatic distant recurrence(HR = 1.49, 95%CI: 1.25-1.77). Subgroupand meta-regression analyses identified various therapeutic modalities as the source of a high degree of heterogeneity. The pooled HR values showed no obvious change when a single study was removed, but otherwise, an opposite-effects model was used. In addition, no significant publication bias was detected.CONCLUSION: Thrombocytopenia before treatment might be an inexpensive and useful predictor of postoperative recurrence in patients with HCC.

Comparison of survival between adolescent and young adult vs older patients with hepatocellular carcinoma

BACKGROUND Due to the special clinical features and biologic characteristics of adolescent and young adult(AYA)cancers,AYA cancers are different from cancers in children and elderly individuals.However,there are few reports on AYA hepatocellular carcinoma(HCC).AIM To investigate the overall survival(OS)of AYA(15-39 years)and elderly(40-74 years)patients with HCC.METHODS The data of all the HCC cases were extracted from the Surveillance,Epidemiology,and End Results database from 2004 to 2015 and were then divided into two groups based on age:AYA group(15-39 years)and older group(40-74 years).Kaplan-Meier curves and log-rank tests were used to compare the OS of the two groups.Propensity score matching(PSM)was employed to analyze the OS difference between the two groups.The Cox proportional hazards regression model was used to perform multivariate analysis to explore the risk factors for OS of HCC patients.RESULTS Compared to elderly cancer patients,AYA patients with HCC had a worse Surveillance,Epidemiology,and End Results stage,including the distant stage(22.1%vs 15.4%,P<0.001),and a more advanced American Joint Committee on Cancer(AJCC)stage,including AJCC III and IV(49.2%vs 38.3%,P<0.001),and were more likely to receive surgery(64.5%vs 47.5%,P<0.001).Before PSM,the AYA group had a longer survival in months(median:20.00,interquartile range[IQR]:5.00-62.50)than the older group(median:15.00,IQR:4.00-40.00)(P<0.001).After PSM,the AYA group still had a longer survival in months(median:21.00,IQR:5.00-64.50)than the older group(median:18.00,IQR:6.00-53.00)(P<0.001).The Cox proportional hazards regression model showed that advanced age(hazard ratio[HR]=1.405,95%CI:1.218-1.621,P<0.001)was a risk factor for OS of HCC patients.In the subgroup analysis,the Cox proportional hazards regression model showed that in AJCC I/II HCC patients,advanced age(HR=1.749,95%CI:1.352-2.263,P<0.001)was a risk factor for OS,while it was not a risk factor in AJCC III/IV HCC patients(HR=1.186,95%CI:0.997-1.410,P=0.054)before PSM.After PSM,advanced age(HR=1.891,95%CI:1.356-2.637,P<0.001)was still a risk factor for OS in AJCC I/II HCC patients,but was not a risk factor for OS in AJCC III/IV HCC patients(HR=1.192,95%CI:0.934-1.521,P=0.157)after PSM.CONCLUSION AYA patients with HCC have different clinical characteristics from older adults.In different AJCC stages,the two groups of patients have different OS:In AJCC I/II HCC patients,advanced age is a risk factor for OS,but it is not a risk factor for OS in the AJCC III/IV HCC patient group.

Liver transplantation versus liver resection for hepatocellular carcinoma: a meta-analysis

BACKGROUND: Liver transplantation(LT) and liver resection(LR) are currently considered the standard treatment of patients with hepatocellular carcinoma(HCC). However, the outcomes of LT and LR are still inconclusive.DATA SOURCES: MEDLINE, EMBASE, and Cochrane Library were searched for relevant studies. Surgical safety indices such as treatment-related morbidity and mortality, and efficacy indices such as overall and tumor-free survival outcomes were evaluated. Weighted mean differences and odds ratios(ORs)were calculated using a random-effects model.RESULTS: Seventeen studies were included in this metaanalysis.LT achieved significantly higher rates of surgeryrelated morbidity(OR=1.47; 95% CI: 1.02-2.13) and mortality(OR=2.12; 95% CI: 1.11-4.05). Likewise, the 1-year survival rate was lower in LT(OR=0.86; 95% CI: 0.61-1.20). However, the 3-and 5-year survival rates were significantly higher in LT than in LR and the ORs were 1.12(95% CI: 0.96-1.30) in 3 years and1.84(95% CI: 1.49-2.28) in 5 years. Furthermore, the tumorfree survival rate in LT was significantly higher than that in LR in 1, 3, 5 years after surgery, with the ORs of 1.72(95% CI:1.24-2.41), 3.75(95% CI: 2.94-4.78) and 5.64(95% CI: 4.35-7.31),respectively.CONCLUSIONS: One-year morbidity and mortality are higher in LT than in LR for patients with HCC. However, long-term survival and tumor-free survival rates are higher in patients treated with LT than those treated with LR.

Fork head box M1 regulates vascular endothelial growth factor-A expression to promote the angiogenesis and tumor cell growth of gallbladder cancer

BACKGROUND Gallbladder cancer(GBC)is an aggressive type of biliary tract cancer that lacks effective therapeutic targets.Fork head box M1(FoxM1)is an emerging molecular target associated with tumor progression in GBC,and accumulating evidence suggests that vascular endothelial growth factor(VEGF)promotes various tumors by inducing neoangiogenesis.AIM To investigate the role of FoxM1 and the angiogenesis effects of VEGF-A in primary GBC.METHODS Using immunohistochemistry,we investigated FoxM1 and VEGF-A expression in GBC tissues,paracarcinoma tissues and cholecystitis tissues.Soft agar,cell invasion,migration and apoptosis assays were used to analyze the malignant phenotype influenced by FoxM1 in GBC.Kaplan-Meier survival analysis was performed to evaluate the impact of FoxM1 and VEGF-A expression in GBC patients.We investigated the relationship between FoxM1 and VEGF-A by regulating the level of FoxM1.Next,we performed MTT assays and Transwell invasion assays by knocking out or overexpressing VEGF-A to evaluate its function in GBC cells.The luciferase assay was used to reveal the relationship between FoxM1 and VEGF-A.BALB/c nude mice were used to establish the xenograft tumor model.RESULTS FoxM1 expression was higher in GBC tissues than in paracarcinoma tissues.Furthermore,the high expression of Foxm1 in GBC was significantly correlated with a malignant phenotype and worse overall survival.Meanwhile,high expression of FoxM1 influenced angiogenesis;high expression of FoxM1 combined with high expression of VEGF-A was related to poor prognosis.Attenuated FoxM1 significantly suppressed cell proliferation,transfer and invasion in vitro.Knockdown of FoxM1 in GBC cells reduced the expression of VEGF-A.Luciferase assay showed that FoxM1 was the transcription factor of VEGF-A,and knockdown VEGF-A in FoxM1 overexpressed cells could partly reverse the malignancy phenotype of GBC cells.In this study,we found that FoxM1 was involved in regulation of VEGF-A expression.CONCLUSION FoxM1 and VEGF-A overexpression were associated with the prognosis of GBC patients.FoxM1 regulated VEGF-A expression,which played an important role in the progression of GBC.

Taipingite-(Ce),(Ce73+,Ca2)∑9Mg(SiO4)3[SiO3(OH)]4F3,a new mineral from the Taipingzhen REE deposit,North Qinling Orogen,central China

A new cerite group mineral species,taipingite-(Ce),ideally(Ce7^3+,Ca2)∑9Mg(SiO4)3[SiO3(OH)]4 F3,has been found in the Taipingzhen rare earth element(REE)deposit in the North Qinling Orogen(NQO),Central China.It forms subhedral grains(up to approximately 100 μm×200 μm)commonly intergrown with the REE mineral assemblages and is closely associated with allanite-(Ce),gatelite-(Ce),tornebohmite-(Ce),fluocerite-(Ce),fluocerite-(La),fluorite,bastnasite-(Ce),parisite-(Ce)and calcite.Taipingite-(Ce)is light red to pinkish brown under a binocular microscope and pale brown to colorless in thin section,and it is translucent to transparent with a grayish-white streak and vitreous luster.This mineral is brittle with conchoidal fracture;has a Mohs hardness value of approximately 51/2 and exhibits no cleavage twinning or parting.The calculated density is 4.900(5)g/cm3.Optically,taipingite-(Ce)is uniaxial(+),withω=1.808(5),ε=1.812(7),c=ε,and a=b=ω.Furthermore,this mineral is insoluble in HCl,HNO3 and H2 SO4.Electron microprobe analysis demonstrated that the sample was relatively pure,yielding the empirical formula(with calculated H2 O):(Ce4.02La1.64Nd1.49Pr0.41Sm0.10Gd0.02Ho0.02Tm0.01Lu0.02Y0.03Ca0.66Mg0.05Th(0.01-0.51∑9(Mg0.75Fe0.253+)∑1(SiO4)3{[SiO3(OH)]3.98[PO3(OH)]0.02}∑4(F1.81OH1.17Cl0.02∑3.Taipingite-(Ce)is trigonal and exhibits space group symmetry R3 c with unit cell parameters a=10.7246(3)Å,c=37.9528(14)Å,V=3780.39(20)Å3 and Z=6.The strongest eight lines in the X-ray diffraction pattern are[d in A(I)(hkl)]:4.518(50)(202),3.455(95)(122),3.297(85)(214),3.098(35)(300),2.941(100)(02,10),2.683(65)(220),1.945(40)(238)and 1.754(40)(30,18).The crystal structure has been refined to a R1 factor of 0.025,calculated for the 2312 unique observed reflections(Fo≥4σ).The mineral is named after its discovery locality and is characterized as the F-dominant analogue of cerite-(Ce).

Sclerosing Cholangitis after Transcatheter Arterial Chemoembolization:a Case Report

SCLEROSING cholangitis represents progressing jaundice or/and paroxysmal symptom of cholangitis, finally developing to end-stage of liver disease. When compared with primary sclerosing cholangitis （PSC）, there are no apparent differences in pathology and clinical manifestation in secondary sclerosing cholangitis （SSC）.

Highlights for α-fetoprotein in determining prognosis and treatment monitoring for hepatocellular carcinoma

AIM:To explore the prognostic value in the monitoring of treatment efficacy of serial α-fetoprotein(AFP) in hepatocellular carcinoma(HCC) patients.METHODS:We searched MEDLINE,EMBASE and COCHRANE LIBRARY through April 21,2012,to find qualifying articles.Our overall search strategy included terms for HCC,AFP,treatment response,and prognosis.Literature was limited to English-language,human studies.Studies reporting cumulative survival rates were summa-rized qualitatively.For the prognostic meta-analysis,we undertook a series of meta-analyses that summarised the Cox proportional hazard ratios(HRs) by assuming a random effects model.With regards to the correlation of AFP change with radiologic response,the categorical dichotomous variables were assessed using Poisson relative risks(RRs),which were incorporated into the random effects model meta-analysis of accuracy prediction.Between-study heterogeneity was estimated by use of the I2 statistic.Publication bias was evaluated using the Begg funnel plot and Egger plot.Sensitivity analyses were conducted first by separating systemic treatment estimates from locoregional therapy estimates,evaluating different AFP response cut-off point effects,and exploring the impact of different study sizes.RESULTS:Of 142 titles identified in our original search,11 articles(12 clinical studies) met our criteria.Six studies investigated outcome in a total of 464 cases who underwent systemic treatment,and six studies investigated outcome in a total of 510 patients who received locoregional therapy.A random-effects model metaanalysis showed that AFP response was associated with an mortality HR of 0.55(95%CI,0.47-0.65) across HCC in overall survival(OS) and 0.50(95%CI,0.38-0.65) in progression-free survival.Restricting analysis to the six eligible analyses of systemic treatment,the pooled HRs were 0.64(95%CI,0.53-0.77) for OS.Limiting analysis to the six analyses of locoregional therapy,the pooled HRs for OS was 0.39(95%CI,0.29-0.53).We showed a larger pooled HR in the 50% definition studies(HR,0.67,95%CI,0.55-0.83) compared with that from the 20% definition studies(HR,0.41,95%CI,0.32-0.53).Restricting analysis to the four studies including over 100 patients individually,the pooled HR was 0.65(95%CI,0.54-0.79),with a pooled HR for OS of 0.35(95%CI,0.23-0.46) in the studies of less than 100 patients.As to radiological imaging,43.1%(155/360) of the patients in the AFP response group presented with a radiological overall response,while the response rate decreased to 11.5%(36/313) in the patients from theAFP nonresponse group.The RR of having no overall response was significantly lower in the AFP response group than the AFP nonresponse group(RR,0.67;95%CI,0.61-0.75).In terms of disease control rate,86.9%(287/330) in the AFP response group and 51.0%(153/300) in the AFP nonresponse group showed successful disease control,respectively.The RR of disease control failure,similarly,was significantly lower in the AFP response group(RR,0.37;95%CI,0.23-0.58).But these findings could be overestimates because of publication and reporting bias.CONCLUSION:HCC patients presenting with an AFP response are at decreased risk of mortality.In addition,patients with an AFP response also present with a higher overall response rate and disease control rate.

Characterizing Poroelasticity of Biological Tissues by Spherical Indentation: An Improved Theory for Large Relaxation

Flow of fluids within biological tissues often meets with resistance that causes a rate-and size-dependent material behavior known as poroelasticity.Characterizing poroelasticity can provide insight into a broad range of physiological functions,and is done qualitatively in the clinic by palpation.Indentation has been widely used for characterizing poroelasticity of soft materials,where quantitative interpretation of indentation requires a model of the underlying physics,and such existingmodels are well established for cases of small strain and modest force relaxationWe showed here that existing models are inadequate for large relaxation,where the force on the indenter at a prescribed depth at long-time scale drops to below half of the initially peak force.We developed an indentation theory for such cases of large relaxation,based upon Biot theory and a generalized Hertz contact model.We demonstrated that proposed theory is suitable for biological tissues(e.g.,spleen,kidney,skin and human cirrhosis liver)with both small and large relaxations.The proposed method would be a powerful tool to characterize poroelastic properties of biological materials for various applications such as pathological study and disease diagnosis.