AIM: To study the expression of hypoxia-inducible factor 1α(HIF-1α) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) and the impact on neovascularization and survival. METHODS: Express...AIM: To study the expression of hypoxia-inducible factor 1α(HIF-1α) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) and the impact on neovascularization and survival. METHODS: Expressions of HIF-1α, VEGF and microvessel density (MVD) are studied through immunohistochemistry in 36 cases of HCC and the corresponding paraneoplastic tissue and 6 cases of normal liver tissue. The relationship of the expressions of HIF-1α and VEGF with the clinicopathological data and survival are analyzed. RESULTS: The positive rate of VEGF in HCC was 32/36, which is significantly higher than that in paraneoplastic tissue and normal liver tissue (P<0.05). The expression of HIF-1aaaaaa in HCC tissue is 24/36, also higher than that in paraneoplastic tissue and normal liver tissue (P<0.05). The expression of VEGF and HIF-1α in HCC with microscopic venous invasion is significantly higher than that in HCC without microscopic venous invasion (P<0.05). Spearman correlation analysis does not only show the expression of HIF-1α as correlated with the expression of VEGF (rs = 0.459, P<0.01), but it also shows the expression of HIF-1α and VEGF as correlated with MVD (rs=0.412 and 0.336, respectively, P<0.05). The differences of the survival rates among VEGF positive group and VEGF negative group are significant (P<0.05), whereas the differences of the survival rates among the HIF-1α negative group and positive group are not significant (P>0.05). CONCLUSION: HIF-1α plays important roles in neovascularization in HCC possibly through regulation of VEGF transcription.展开更多
BACKGROUND: Liver transplantation is one of the most effective therapeutic options for patients with end-stage liver diseases, and gut microbiota is actively involved in potential infections in pretransplant and postt...BACKGROUND: Liver transplantation is one of the most effective therapeutic options for patients with end-stage liver diseases, and gut microbiota is actively involved in potential infections in pretransplant and posttransplant patients. However, the diversity of gut microbiota and its relationship with the immune parameter of liver transplantation recipients are not well understood. METHODS: We collected fresh feces and blood samples from 190 participants in China from November 2004 to May 2008, including 28 healthy volunteers, 51 cirrhotic patients and 111 liver-transplanted patients. Six interesting gut bacteria, plasma endotoxin, serum cytokines (i.e., tumor necrosis factor alpha and interleukin-6) and fecal secretory IgA (SIgA) were investigated by real-time quantitative PCR, chromogenic limulus amoebocyte assay, sandwich-type enzyme-linked immunosorbent assay and radioimmunoassay, respectively. RESULTS: All Eubacteria, Bifidobacterium spp., Faecalibacterium prausnitzii and Lactobacillus spp. were significantly lower in the liver transplantation recipients while Enterobacteriaceae and Enterococcus spp. were significantly higher (P<0.05). Except for Enterococcus spp., other bacteria showed a tendency to restore to normal level along with the time after liver transplantation. Plasma endotoxin, interleukin-6 and fecal SIgA in cirrhotic patients increased significantly, but not in liver transplantation recipients. Plasma endotoxin and interleukin-6 were negatively correlated with all Eubacteria and the Bacteroides-Prevotella group, while tumor necrosis factor alpha was not significantly correlated with these six gut bacteria in cirrhotic patients.CONCLUSIONS: Our study demonstrates that abundant gut bacteria were altered significantly in both cirrhotic and liver transplantation patients, while plasma endotoxin and interleukin-6 increased remarkably in cirrhotic patients, showing significant correlations with gut microbiota. Interestingly, our data show a tendency for these gut bacteria to restore to normal levels展开更多
AIM： To investigate the suppressive effect of saikosaponin-d （SSd） on hepatic fibrosis in rats induced by CCh injections in combination with alcohol and high fat, low protein feeding and its relationship with the e...AIM： To investigate the suppressive effect of saikosaponin-d （SSd） on hepatic fibrosis in rats induced by CCh injections in combination with alcohol and high fat, low protein feeding and its relationship with the expression of nuclear factor-κB （NF-κB）, tumor necrosis factor-alpha （TNF-α） and interleukins-6 （IL-6）. METHODS： Hepatic fibrosis models were induced by subcutaneous injection of CCh at a dosage of 3 mL/kg in rats. At the same time, rats in treatment groups were injected intraperitoneally with SSd at different doses （1.0, 1.5 and 2.0 mg/kg） once daily for 6 wk in combination with CCh, while the control group received olive oil instead of CCh. At the end of the experiment, rats were anesthetized and killed （except for 8 rats which died during the experiment; 2 from the model group, 3 in high-dose group, 1 in medium-dose group and 2 in lowdose group）. Hernatoxylin and eosin （HE） staining and Van Gieson staining were used to examine the changes in liver pathology. The levels of alanine aminotransferase （ALT）, triglyeride （TG）, albumin （ALB）, globulin （GLB）, hyaluronic acid （HA） and larninin （LN） in serum and the content of hydroxyproline （HYP） in liver were measured by biochemical examinations and radioimmuneoassay, respectively. In addition, the expression of TNF-α and IL-6 in liver homogenate was evaluated by enzymelinked immunosorbent assay （ELISA） and the levels of NF-κBp65 and I-κBa in liver tissue were analyzed by Western blotting. RESULTS： Both histological examination and Van Gieson staining demonstrated that SSd could attenuate the area and extent of necrosis and reduce the scores of liver fibrosis. Similarly, the levels of ALT, TG, GLB, HA, and LN in serum, and the contents of HYP, TNF-α and IL-6 in liver were all significantly increased in model group in comparison with those in control group. Whereas, the treatment with SScl markedly reduced all the above parameters compared with the model group, especially in the medium gr展开更多
Aims Understanding what drives the variation in species composition and diversity among local communities can provide insights into the mechanisms of community assembly.Because ecological traits are often thought to b...Aims Understanding what drives the variation in species composition and diversity among local communities can provide insights into the mechanisms of community assembly.Because ecological traits are often thought to be phylogenetically conserved,there should be patterns in phylogenetic structure and phylogenetic diversity in local communities along ecological gradients.We investigate potential patterns in angiosperm assemblages along an elevational gradient with a steep ecological gradient in Changbaishan,China.Methods We used 13 angiosperm assemblages in forest plots(32×32 m)distributed along an elevational gradient from 720 to 1900 m above sea level.We used Faith’s phylogenetic diversity metric to quantify the phylogenetic alpha diversity of each forest plot,used the net relatedness index to quantify the degree of phylogenetic relatedness among angiosperm species within each forest plot and used a phylogenetic dissimilarity index to quantify phylogenetic beta diversity among forest plots.We related the measures of phylogenetic structure and phylogenetic diversity to environmental(climatic and edaphic)factors.Important Findings Our study showed that angiosperm assemblages tended to be more phylogenetically clustered at higher elevations in Changbaishan.This finding is consistent with the prediction of the phylogenetic niche conservatism hypothesis,which highlights the role of niche constraints in governing the phylogenetic structure of assemblages.Our study also showed that woody assemblages differ from herbaceous assemblages in several major aspects.First,phylogenetic clustering dominated in woody assemblages,whereas phylogenetic overdispersion dominated in herbaceous assemblages;second,patterns in phylogenetic relatedness along the elevational and temperature gradients of Changbaishan were stronger for woody assemblages than for herbaceous assemblages;third,environmental variables explained much more variations in phylogenetic relatedness,phylogenetic alpha diversity and phylogenetic beta diversity for wood展开更多
Objective To investigate the expression levels of serum hypoxia inducible factor 1 alpha(HIF-1α) and vascular endothelial growth factor(VEGF) pre-and post-transcatheter arterial chemoembolization(TACE) in patients wi...Objective To investigate the expression levels of serum hypoxia inducible factor 1 alpha(HIF-1α) and vascular endothelial growth factor(VEGF) pre-and post-transcatheter arterial chemoembolization(TACE) in patients with primary liver cancer(PLC),and correlations between prognosis factors and serum HIF-1α as well as VEGF levels.Methods Forty consecutive patients fulfilling diagnostic criteria for PLC undergoing TACE from March 2008 to May 2009 were enrolled into the study.The serum HIF-1α and VEGF levels of PLC patients pre-and 1 day,1 week,1 month post-TACE were analyzed using ELISA,and compared with that of 20 healthy volunteers.Patients were divided into complete response(CR) and partial response(PR),stable disease(SD),progressive disease(PD) groups according to the therapeutic efficacy.Pearson correlation was used to analyze the correlation between different clinical variables and serum HIF-1α and VEGF levels before TACE,and correlation between serum HIF-1α and VEGF levels was also evaluated.Results The expression levels of serum HIF-1α and VEGF in PLC patients were 154.94±83.29 and 264.00±148.10 pg/mL pre-TACE,and both of them were significantly higher than those in control group(23.84±8.15 and 69.78±21.42 pg/mL,all P<0.01).One day after TACE,both serum HIF-1α(570.64± 230.87 pg/mL) and VEGF levels(362.07±102.25 pg/mL) reached the peak values(all P<0.01).One week post-TACE,expression levels of them were decreased(198.62±92.11 and 283.52±145.46 pg/mL respectively),but still significantly higher than those before TACE(all P<0.01).The levels of both HIF-1α(133.96±57.02 vs.255.74±123.44 pg/mL) and VEGF(150.96±84.89 vs.368.95±161.90 pg/mL) in CR group 1 month post-TACE were significantly lower than those in PR+SD+PD group(all P<0.01).The level of serum HIF-1α was positively correlated with serum VEGF level(r=0.42,P<0.001).Both serum HIF-1α and VEGF levels were observed to be correlated with portal vein tumor thrombi(P<0.05) and metastasis(P<0.05).展开更多
Background Aspirin can inhibit inflammatory reactions and platelet aggregation, but little is known about the effects of the combination of aspirin plus clopidogrel, a new antiplatelet agent, on inflammation. The purp...Background Aspirin can inhibit inflammatory reactions and platelet aggregation, but little is known about the effects of the combination of aspirin plus clopidogrel, a new antiplatelet agent, on inflammation. The purpose of this study was to determine whether aspirin plus clopidogrel can further suppress inflammation in patients with non-ST-segment elevation acute coronary syndrome （NSTEACS）. Methods One hundred and fifteen patients with NSTEACS were randomized into two groups： group A （aspirin alone, n=58） and group B （aspirin plus clopidogrel, n=57）. Patients in group A received a loading dose of 300 mg aspirin, then 100 mg per day. The patients in group B received a loading dose of 300 mg aspirin and 300 mg clopidogrel, then 100 mg aspirin and 75 mg clopidogrel per day. Serum high sensitivity C-reactive protein （hs-CRP） and tumor necrosis factor-α （TNF-α ） were measured in all patients at baseline prior to any drug treatment after admission, and at 7 and 30 days after beginning drug treatment. Thirty healthy volunteers on no medications were enrolled as controls （group C）. Results Baseline levels of hs-CRP and TNF-α in group A and group B were significantly higher than those in group C. Seven days after administration, the levels of hs-CRP in both group A and group B decreased significantly [Group A： （6.15 ± 1.39） mg/L vs （9.18 ± 1.62） rag/L, P 〈0.01; Group B：（4.99 ± 1.62） mg/L vs （10.29 ± 1.47） rag/L, P〈0.01]. Similarly, levels of TNF-α in both groups decreased at 7 days compared to baseline [Group A： （90.99 ± 28.91） pg/ml vs （117.20 ± 37.13） pg/ml, P 〈0.01; Group B： （74.32± 21.83） pg/ml vs （115.27 ± 32.11） pg/ml, P 〈0.01]. Thirty days after administration, the levels of hs-CRP in both group A and group B decreased further to （3.49 ± 1.53） rag/L, and （2.40 ± 1.17） mg/L respectively （P 〈0.01 for both comparisons）. Levels of TNF-α in groups A and B also decreased significantly between 7 and 30 days, to 63.28 �展开更多
Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and have gained considerable research and treatment interest,especially in the last two decades. GISTs are dr...Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and have gained considerable research and treatment interest,especially in the last two decades. GISTs are driven by mutations commonly found in the KIT gene and less commonly in the platelet-derived growth factor receptor alpha gene,BRAF gene and succinate dehydrogenase gene. GISTs behave in a spectrum of malignant potential,and both the tumor size and mitotic index are the most commonly used prognostic criteria. Whilst surgical resection can offer the best cure,targeted therapy in the form of tyrosine kinase inhibitors(TKIs) has revolutionized the management options. As the first-line TKI,imatinib offers treatment for advanced and metastatic GISTs,adjuvant therapy in high-risk GISTs and as a neoadjuvant agent to downsize large tumors prior to resection. The emergence of drug resistance has altered some treatment options,including prolonging the first-line TKI from 1 to 3 years,increasing the dose of TKI or switching to second-line TKI. Other newer TKIs,such as sunitinib and regorafenib,may offer some treatment options for imatinib-resistant GISTs. New molecular targeted therapies are being evaluated,such as inhibitors of BRAF,heat shock protein 90,glutamine and mitogenactivated protein kinase signaling,as well as inhibitors of apoptosis proteins antagonist and even immunotherapy. This editorial review summarizes the recent research trials and potential treatment targets that may influence our future patient-specific management of GISTs. The current guidelines in GIST management from Europe,North America and Asia are highlighted.展开更多
AIM: To examine whether vitamin D improved viral response and predicted treatment outcome in patients with hepatitis C virus (HCV) genotype 2-3. METHODS: Fifty patients with chronic HCV genotype 2-3 were randomized co...AIM: To examine whether vitamin D improved viral response and predicted treatment outcome in patients with hepatitis C virus (HCV) genotype 2-3. METHODS: Fifty patients with chronic HCV genotype 2-3 were randomized consecutively into two groups: Treatment group [20 subjects, age 48 ± 14 years, body mass index (BMI) 30 ± 6, 65% male], who received 180 μg pegylated α-interferon-2a plus oral ribavirin 800 mg/d (Peg/RBV), together with oral vitamin D3 (Vitamidyne D drops; 2000 IU/d, 10 drops/d, normal serum level > 32 ng/mL) for 24 wk; and control group (30 subjects, age 45 ± 10 years, BMI 26 ± 3, 60% male), who received identical therapy without vitamin D. HCV RNA was assessed by reverse transcription polymerase chain reaction. Undetectable HCV RNA at 4, 12 and 24 wk after treatment was considered as rapid virological response, complete early virological response, and sustained virological response (SVR), respectively. Biomarkers of in? ammation were measured. RESULTS: The treatment group with vitamin D hadhigher BMI (30 ± 6 vs 26 ± 3, P < 0.02), and high viral load (> 400 000 IU/mL, 65% vs 40%, P < 0.01) than controls. Ninety-fi ve percent of treated patients were HCV RNA negative at week 4 and 12. At 24 wk after treatment (SVR), 19/20 (95%) treated patients and 23/30 (77%) controls were HCV RNA negative (P < 0.001). Baseline serum vitamin D levels were lower at baseline (20 ± 8 ng/mL) and increased after 12 wk vitamin D treatment, to a mean level of (34 ± 11 ng/ mL). Logistic regression analysis identifi ed vitamin D supplement [odds ratio (OR) 3.0, 95% CI 2.0-4.9, P < 0.001], serum vitamin D levels (< 15 or > 15 ng/mL, OR 2.2, P < 0.01), and BMI (< 30 or > 30, OR 2.6, P < 0.01) as independent predictors of viral response. Adverse events were mild and typical of Peg/RBV. CONCLUSION: Low vitamin D levels predicts negative treatment outcome, and adding vitamin D to conventional Peg/RBV therapy for patients with HCV genotype 2-3 signifi cantly improves viral response.展开更多
Hepatocellular carcinoma(HCC) is one of the most commonly diagnosed and deadly cancers worldwide; its incidence has been rising in the United States due to the increase in hepatitis C associated cirrhosis and the grow...Hepatocellular carcinoma(HCC) is one of the most commonly diagnosed and deadly cancers worldwide; its incidence has been rising in the United States due to the increase in hepatitis C associated cirrhosis and the growing epidemic of obesity. There have been no effective therapeutic options in the advanced disease setting beyond sorafenib, a multi-targeted tyrosine kinase inhibitor that showed significant survival benefit. Because of this, there is an urgent need to search for novel pathways in sorafenib experienced patients. This review will focus on the role of hypoxia and hypoxiainducible factor alpha(HIF-1α) in cancer development, specifically in HCC. We will discuss the biology of HIF-1α, the pathways with which it interacts, and the function of HIF-1α in HCC. Furthermore, we will review studies highlighting the relevance of HIF-1α in the clinical setting, as well as the pre-clinical data supporting its further investigation. Finally, we will conclude with a discussion of the potential role of a HIF-1α m RNA antagonist for the treatment of HCC, and hypothesize the ways in which such an inhibitor may be best utilized in the management of advanced HCC. Hypoxia plays a significant role in the development of HCC. HIF-1α is a key transcription factor involved in the hypoxic response of cancer cells. It activates transcription of genes responsible for angiogenesis, glucose metabolism, proliferation, invasion and metastasis in HCC. Its involvement in multiple, essential tumor pathways makes it an attractive potential therapeutic target in HCC.展开更多
AIM:To investigate the biological role of alpha fetoprotein (AFP) and its clinical signif icance in carcinogenesis of hepatocellular carcinoma (HCC).METHODS:Clinical analysis of HCC patients and im-munohistochemical e...AIM:To investigate the biological role of alpha fetoprotein (AFP) and its clinical signif icance in carcinogenesis of hepatocellular carcinoma (HCC).METHODS:Clinical analysis of HCC patients and im-munohistochemical examination were conducted to evaluate the relationship between serum AFP level and patient mortality. Confocal microscopy,Western blotting, dimethylthiahzolyl-2,5-diphenyl-tetrazolium bromide,Cell Counting Kit-8 assays and flow cytometry were performed to explore the possible mechanism.RESULTS: Among the 160 HCC patients enrolled in this study,130 patients survived 2 years (81.25%),with a survival rate of 86.8% in AFP < 2 0 μg/L group,88.9% in AFP 20-250 μg/L group,and 69.6% in AFP > 250 μg/L group, demonstrating a higher mortality rate in HCC patients with higher AFP levels. Surgical treatment was benef icial only in patients with low AFP levels.The mortality rate of HCC patients with high AFP levels who were treated surgically was apparently higher than those treated with conservative management.The results of immunohistochemistry showed that AFP and AFP receptor were merely expressed in tissues of HCC patients with positive serum AFP.Consistently,in vitro analysis showed that AFP and AFPS were expressed in HepG2 but not in HLE cells. AFP showed a capability to promote cell growth,and this was more apparent in HepG2 cells,in which the proliferation was increased by 3.5 folds. Cell cycle analysis showed that the percent-age of HepG2 cells in S phase after exposure to AFP was modestly increased.CONCLUSION:HCC patients with higher AFP levels show a higher mortality rate,which appears to be attributable to the growth promoting properties of AFP.展开更多
Lipoxin A4 can alleviate cerebral ischemia/reperfusion injury by reducing the inflammatory reaction,but it is currently unclear whether it has a protective effect on diabetes mellitus complicated by focal cerebral isc...Lipoxin A4 can alleviate cerebral ischemia/reperfusion injury by reducing the inflammatory reaction,but it is currently unclear whether it has a protective effect on diabetes mellitus complicated by focal cerebral ischemia/reperfusion injury.In this study,we established rat models of diabetes mellitus using an intraperitoneal injection of streptozotocin.We then induced focal cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours.After administration of lipoxin A4 via the lateral ventricle,infarction volume was reduced,the expression levels of pro-inflammatory factors tumor necrosis factor alpha and nuclear factor-kappa B in the cerebral cortex were decreased,and neurological functioning was improved.These findings suggest that lipoxin A4 has strong neuroprotective effects in diabetes mellitus complicated by focal cerebral ischemia/reperfusion injury and that the underlying mechanism is related to the anti-inflammatory action of lipoxin A4.展开更多
AIM To determine the tumor necrosis factor alpha (TNFα), interleukin 6 (IL 6) and soluble interleukin 2 receptor (sIL 2r) from peripheral blood mononuclear cells (PBMC) in 25 Chinese patients with ulcerative colit...AIM To determine the tumor necrosis factor alpha (TNFα), interleukin 6 (IL 6) and soluble interleukin 2 receptor (sIL 2r) from peripheral blood mononuclear cells (PBMC) in 25 Chinese patients with ulcerative colitis and 20 healthy controls. METHODS PBMC were isolated by density gradient centrifugation of heparinized blood and cultures for 24 or 48 hours by stimulation with LPS or PHA. TNFα and sIL 2r were measured by ELISA method and IL 6 measured by bioassay. RESULTS TNFα production stimulated by LPS and sIL 2r production by PHA in ulcerative colitis were significantly lower than in healthy controls (TNFα 509(46-7244)ng/L vs 1995(117-18 950)ng/L, P <0 05; sIL 2r 320U/ml±165U/ml vs 451U/ml±247U/ml, P <0 05). Spontaneous TNFα and sIL 2r production were not significantly different between ulcerative colitis and controls (TNFα 304(46-7044)ng/L vs 215(46-4009)ng/L, P >0 05; sIL 2r 264U/ml±115U/ml vs 236U/ml±139U/ml, P >0 05). IL 6 production by spontaneous release from PBMC in ulcerative colitis group was 109U/ml±94U/ml vs 44U/ml±39U/ml for those in healthy controls, P <0 01. IL 6 stimulated by LPS in ulcerative colitis group was (261U/ml±80U/ml) higher than in healthy controls (102U/ml±54U/ml, P <0 01). No correlation of TNFα, IL 6, sIL 2r production was found to disease activity, disease location and medication. CONCLUSION Cytokine production from PBMC was also disturbed in Chinese patients with ulcerative colitis.展开更多
AIM:To investigate human epidermal growth factor receptor 2(HER2)-phosphatidylinositol 3-kinase(PI3K)-vAkt murine thymoma viral oncogene homolog signaling pathway.METHODS:We analyzed 231 formalin-fixed,paraffinembedde...AIM:To investigate human epidermal growth factor receptor 2(HER2)-phosphatidylinositol 3-kinase(PI3K)-vAkt murine thymoma viral oncogene homolog signaling pathway.METHODS:We analyzed 231 formalin-fixed,paraffinembedded gastric cancer tissue specimens from Japanese patients who had undergone surgical treatment.The patients' age,sex,tumor location,depth of invasion,pathological type,lymph node metastasis,and pathological stage were determined by a review of the medical records.Expression of HER2 was analyzed by immunohistochemistry(IHC) using the HercepTest TM kit.Standard criteria for HER2 positivity(0,1+,2+,and 3+) were used.Tumors that scored 3+ were considered HER2-positive.Expression of phospho Akt(pAkt) was also analyzed by IHC.Tumors were considered pAkt-positive when the percentage of positive tumor cells was 10% or more.PI3K,catalytic,alpha polypeptide(PIK3CA) mutations in exons 1,9 and 20 were analyzed by pyrosequencing.Epstein-Barr virus(EBV) infection was analyzed by in situ hybridization targeting EBV-encoded small RNA(EBER) with an EBER-RNA probe.Microsatellite instability(MSI) was analyzed by polymerase chain reaction using the mononucleotide markers BAT25 and BAT26.RESULTS:HER2 expression levels of 0,1+,2+ and 3+ were found in 167(72%),32(14%),12(5%) and 20(8.7%) samples,respectively.HER2 overexpression(IHC 3+) significantly correlated with intestinal histological type(15/20 vs 98 /205,P = 0.05).PIK3CA mutations were present in 20 cases(8.7%) and significantly correlated with MSI(10/20 vs 9/211,P < 0.01).The mutation frequency was high(21%) in T4 cancers and very low(6%) in T2 cancers.Mutations in exons 1,9 and 20 were detected in 5(2%),9(4%) and 7(3%) cases,respectively.Two new types of PIK3CA mutation,R88Q and R108H,were found in exon1.All PIK3CA mutations were heterozygous missense singlebase substitutions,the most common being H1047R(6/20,30%) in exon20.Eighteen cancers(8%) were EBV-positive and this positivity significantly correlated with a diffuse histological type(13/18 vs 93/198,P = 0.04).T展开更多
精确分割建筑物屋顶激光雷达(light detection and ranging,LiDAR)点云是三维模型重建的重要环节。针对现有算法分割复杂建筑物屋顶面结构精度差的问题,提出一种以三角面为基元的基于区域生长算法的复杂建筑物屋顶点云分割方法。首先,构...精确分割建筑物屋顶激光雷达(light detection and ranging,LiDAR)点云是三维模型重建的重要环节。针对现有算法分割复杂建筑物屋顶面结构精度差的问题,提出一种以三角面为基元的基于区域生长算法的复杂建筑物屋顶点云分割方法。首先,构建Delaunay三角网建立各激光点间相互关系,计算各三角面法向量,利用同一建筑物面片上各三角面法向量基本一致的特征对点云进行初步划分;然后,由于点云散乱性及误差影响产生诸多散乱三角面,对各构成散乱三角面的点进行剖分,并基于具有良好鲁棒性的随机采样一致性算法(random sample consensus,RANSAC),结合Alpha Shape算法获取建筑物各面片边界,合并过度分割的面片及孤立点,完成建筑物屋顶点云分割。实验结果表明,该方法对复杂建筑物屋顶点云分割的完整性、正确性及质量均较为理想。展开更多
文摘AIM: To study the expression of hypoxia-inducible factor 1α(HIF-1α) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) and the impact on neovascularization and survival. METHODS: Expressions of HIF-1α, VEGF and microvessel density (MVD) are studied through immunohistochemistry in 36 cases of HCC and the corresponding paraneoplastic tissue and 6 cases of normal liver tissue. The relationship of the expressions of HIF-1α and VEGF with the clinicopathological data and survival are analyzed. RESULTS: The positive rate of VEGF in HCC was 32/36, which is significantly higher than that in paraneoplastic tissue and normal liver tissue (P<0.05). The expression of HIF-1aaaaaa in HCC tissue is 24/36, also higher than that in paraneoplastic tissue and normal liver tissue (P<0.05). The expression of VEGF and HIF-1α in HCC with microscopic venous invasion is significantly higher than that in HCC without microscopic venous invasion (P<0.05). Spearman correlation analysis does not only show the expression of HIF-1α as correlated with the expression of VEGF (rs = 0.459, P<0.01), but it also shows the expression of HIF-1α and VEGF as correlated with MVD (rs=0.412 and 0.336, respectively, P<0.05). The differences of the survival rates among VEGF positive group and VEGF negative group are significant (P<0.05), whereas the differences of the survival rates among the HIF-1α negative group and positive group are not significant (P>0.05). CONCLUSION: HIF-1α plays important roles in neovascularization in HCC possibly through regulation of VEGF transcription.
基金supported by the grants from the National Basic Research Program of China (973 program) (2007CB513003)Zhejiang Provincial Science and Technology Bureau Project(2006C23017)
文摘BACKGROUND: Liver transplantation is one of the most effective therapeutic options for patients with end-stage liver diseases, and gut microbiota is actively involved in potential infections in pretransplant and posttransplant patients. However, the diversity of gut microbiota and its relationship with the immune parameter of liver transplantation recipients are not well understood. METHODS: We collected fresh feces and blood samples from 190 participants in China from November 2004 to May 2008, including 28 healthy volunteers, 51 cirrhotic patients and 111 liver-transplanted patients. Six interesting gut bacteria, plasma endotoxin, serum cytokines (i.e., tumor necrosis factor alpha and interleukin-6) and fecal secretory IgA (SIgA) were investigated by real-time quantitative PCR, chromogenic limulus amoebocyte assay, sandwich-type enzyme-linked immunosorbent assay and radioimmunoassay, respectively. RESULTS: All Eubacteria, Bifidobacterium spp., Faecalibacterium prausnitzii and Lactobacillus spp. were significantly lower in the liver transplantation recipients while Enterobacteriaceae and Enterococcus spp. were significantly higher (P<0.05). Except for Enterococcus spp., other bacteria showed a tendency to restore to normal level along with the time after liver transplantation. Plasma endotoxin, interleukin-6 and fecal SIgA in cirrhotic patients increased significantly, but not in liver transplantation recipients. Plasma endotoxin and interleukin-6 were negatively correlated with all Eubacteria and the Bacteroides-Prevotella group, while tumor necrosis factor alpha was not significantly correlated with these six gut bacteria in cirrhotic patients.CONCLUSIONS: Our study demonstrates that abundant gut bacteria were altered significantly in both cirrhotic and liver transplantation patients, while plasma endotoxin and interleukin-6 increased remarkably in cirrhotic patients, showing significant correlations with gut microbiota. Interestingly, our data show a tendency for these gut bacteria to restore to normal levels
基金the National Natural Science Foundation of China, No. 30471982
文摘AIM： To investigate the suppressive effect of saikosaponin-d （SSd） on hepatic fibrosis in rats induced by CCh injections in combination with alcohol and high fat, low protein feeding and its relationship with the expression of nuclear factor-κB （NF-κB）, tumor necrosis factor-alpha （TNF-α） and interleukins-6 （IL-6）. METHODS： Hepatic fibrosis models were induced by subcutaneous injection of CCh at a dosage of 3 mL/kg in rats. At the same time, rats in treatment groups were injected intraperitoneally with SSd at different doses （1.0, 1.5 and 2.0 mg/kg） once daily for 6 wk in combination with CCh, while the control group received olive oil instead of CCh. At the end of the experiment, rats were anesthetized and killed （except for 8 rats which died during the experiment; 2 from the model group, 3 in high-dose group, 1 in medium-dose group and 2 in lowdose group）. Hernatoxylin and eosin （HE） staining and Van Gieson staining were used to examine the changes in liver pathology. The levels of alanine aminotransferase （ALT）, triglyeride （TG）, albumin （ALB）, globulin （GLB）, hyaluronic acid （HA） and larninin （LN） in serum and the content of hydroxyproline （HYP） in liver were measured by biochemical examinations and radioimmuneoassay, respectively. In addition, the expression of TNF-α and IL-6 in liver homogenate was evaluated by enzymelinked immunosorbent assay （ELISA） and the levels of NF-κBp65 and I-κBa in liver tissue were analyzed by Western blotting. RESULTS： Both histological examination and Van Gieson staining demonstrated that SSd could attenuate the area and extent of necrosis and reduce the scores of liver fibrosis. Similarly, the levels of ALT, TG, GLB, HA, and LN in serum, and the contents of HYP, TNF-α and IL-6 in liver were all significantly increased in model group in comparison with those in control group. Whereas, the treatment with SScl markedly reduced all the above parameters compared with the model group, especially in the medium gr
基金China National Scientific and Technical Foundation Project(2012FY112000 to Z.H.)。
文摘Aims Understanding what drives the variation in species composition and diversity among local communities can provide insights into the mechanisms of community assembly.Because ecological traits are often thought to be phylogenetically conserved,there should be patterns in phylogenetic structure and phylogenetic diversity in local communities along ecological gradients.We investigate potential patterns in angiosperm assemblages along an elevational gradient with a steep ecological gradient in Changbaishan,China.Methods We used 13 angiosperm assemblages in forest plots(32×32 m)distributed along an elevational gradient from 720 to 1900 m above sea level.We used Faith’s phylogenetic diversity metric to quantify the phylogenetic alpha diversity of each forest plot,used the net relatedness index to quantify the degree of phylogenetic relatedness among angiosperm species within each forest plot and used a phylogenetic dissimilarity index to quantify phylogenetic beta diversity among forest plots.We related the measures of phylogenetic structure and phylogenetic diversity to environmental(climatic and edaphic)factors.Important Findings Our study showed that angiosperm assemblages tended to be more phylogenetically clustered at higher elevations in Changbaishan.This finding is consistent with the prediction of the phylogenetic niche conservatism hypothesis,which highlights the role of niche constraints in governing the phylogenetic structure of assemblages.Our study also showed that woody assemblages differ from herbaceous assemblages in several major aspects.First,phylogenetic clustering dominated in woody assemblages,whereas phylogenetic overdispersion dominated in herbaceous assemblages;second,patterns in phylogenetic relatedness along the elevational and temperature gradients of Changbaishan were stronger for woody assemblages than for herbaceous assemblages;third,environmental variables explained much more variations in phylogenetic relatedness,phylogenetic alpha diversity and phylogenetic beta diversity for wood
文摘Objective To investigate the expression levels of serum hypoxia inducible factor 1 alpha(HIF-1α) and vascular endothelial growth factor(VEGF) pre-and post-transcatheter arterial chemoembolization(TACE) in patients with primary liver cancer(PLC),and correlations between prognosis factors and serum HIF-1α as well as VEGF levels.Methods Forty consecutive patients fulfilling diagnostic criteria for PLC undergoing TACE from March 2008 to May 2009 were enrolled into the study.The serum HIF-1α and VEGF levels of PLC patients pre-and 1 day,1 week,1 month post-TACE were analyzed using ELISA,and compared with that of 20 healthy volunteers.Patients were divided into complete response(CR) and partial response(PR),stable disease(SD),progressive disease(PD) groups according to the therapeutic efficacy.Pearson correlation was used to analyze the correlation between different clinical variables and serum HIF-1α and VEGF levels before TACE,and correlation between serum HIF-1α and VEGF levels was also evaluated.Results The expression levels of serum HIF-1α and VEGF in PLC patients were 154.94±83.29 and 264.00±148.10 pg/mL pre-TACE,and both of them were significantly higher than those in control group(23.84±8.15 and 69.78±21.42 pg/mL,all P<0.01).One day after TACE,both serum HIF-1α(570.64± 230.87 pg/mL) and VEGF levels(362.07±102.25 pg/mL) reached the peak values(all P<0.01).One week post-TACE,expression levels of them were decreased(198.62±92.11 and 283.52±145.46 pg/mL respectively),but still significantly higher than those before TACE(all P<0.01).The levels of both HIF-1α(133.96±57.02 vs.255.74±123.44 pg/mL) and VEGF(150.96±84.89 vs.368.95±161.90 pg/mL) in CR group 1 month post-TACE were significantly lower than those in PR+SD+PD group(all P<0.01).The level of serum HIF-1α was positively correlated with serum VEGF level(r=0.42,P<0.001).Both serum HIF-1α and VEGF levels were observed to be correlated with portal vein tumor thrombi(P<0.05) and metastasis(P<0.05).
基金THIS STUDY WAS SUPPORTED BY THE KEY CLINICAL PROJECT OF THE CHINESE MINISTRY OF HEALTH(NO.20012943) AND THE NATIONAL SCIENCE FOUNDATION OF SHANDONG PROVINCE(NO.2002BB1CJA1)
文摘Background Aspirin can inhibit inflammatory reactions and platelet aggregation, but little is known about the effects of the combination of aspirin plus clopidogrel, a new antiplatelet agent, on inflammation. The purpose of this study was to determine whether aspirin plus clopidogrel can further suppress inflammation in patients with non-ST-segment elevation acute coronary syndrome （NSTEACS）. Methods One hundred and fifteen patients with NSTEACS were randomized into two groups： group A （aspirin alone, n=58） and group B （aspirin plus clopidogrel, n=57）. Patients in group A received a loading dose of 300 mg aspirin, then 100 mg per day. The patients in group B received a loading dose of 300 mg aspirin and 300 mg clopidogrel, then 100 mg aspirin and 75 mg clopidogrel per day. Serum high sensitivity C-reactive protein （hs-CRP） and tumor necrosis factor-α （TNF-α ） were measured in all patients at baseline prior to any drug treatment after admission, and at 7 and 30 days after beginning drug treatment. Thirty healthy volunteers on no medications were enrolled as controls （group C）. Results Baseline levels of hs-CRP and TNF-α in group A and group B were significantly higher than those in group C. Seven days after administration, the levels of hs-CRP in both group A and group B decreased significantly [Group A： （6.15 ± 1.39） mg/L vs （9.18 ± 1.62） rag/L, P 〈0.01; Group B：（4.99 ± 1.62） mg/L vs （10.29 ± 1.47） rag/L, P〈0.01]. Similarly, levels of TNF-α in both groups decreased at 7 days compared to baseline [Group A： （90.99 ± 28.91） pg/ml vs （117.20 ± 37.13） pg/ml, P 〈0.01; Group B： （74.32± 21.83） pg/ml vs （115.27 ± 32.11） pg/ml, P 〈0.01]. Thirty days after administration, the levels of hs-CRP in both group A and group B decreased further to （3.49 ± 1.53） rag/L, and （2.40 ± 1.17） mg/L respectively （P 〈0.01 for both comparisons）. Levels of TNF-α in groups A and B also decreased significantly between 7 and 30 days, to 63.28 �
文摘Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and have gained considerable research and treatment interest,especially in the last two decades. GISTs are driven by mutations commonly found in the KIT gene and less commonly in the platelet-derived growth factor receptor alpha gene,BRAF gene and succinate dehydrogenase gene. GISTs behave in a spectrum of malignant potential,and both the tumor size and mitotic index are the most commonly used prognostic criteria. Whilst surgical resection can offer the best cure,targeted therapy in the form of tyrosine kinase inhibitors(TKIs) has revolutionized the management options. As the first-line TKI,imatinib offers treatment for advanced and metastatic GISTs,adjuvant therapy in high-risk GISTs and as a neoadjuvant agent to downsize large tumors prior to resection. The emergence of drug resistance has altered some treatment options,including prolonging the first-line TKI from 1 to 3 years,increasing the dose of TKI or switching to second-line TKI. Other newer TKIs,such as sunitinib and regorafenib,may offer some treatment options for imatinib-resistant GISTs. New molecular targeted therapies are being evaluated,such as inhibitors of BRAF,heat shock protein 90,glutamine and mitogenactivated protein kinase signaling,as well as inhibitors of apoptosis proteins antagonist and even immunotherapy. This editorial review summarizes the recent research trials and potential treatment targets that may influence our future patient-specific management of GISTs. The current guidelines in GIST management from Europe,North America and Asia are highlighted.
文摘AIM: To examine whether vitamin D improved viral response and predicted treatment outcome in patients with hepatitis C virus (HCV) genotype 2-3. METHODS: Fifty patients with chronic HCV genotype 2-3 were randomized consecutively into two groups: Treatment group [20 subjects, age 48 ± 14 years, body mass index (BMI) 30 ± 6, 65% male], who received 180 μg pegylated α-interferon-2a plus oral ribavirin 800 mg/d (Peg/RBV), together with oral vitamin D3 (Vitamidyne D drops; 2000 IU/d, 10 drops/d, normal serum level > 32 ng/mL) for 24 wk; and control group (30 subjects, age 45 ± 10 years, BMI 26 ± 3, 60% male), who received identical therapy without vitamin D. HCV RNA was assessed by reverse transcription polymerase chain reaction. Undetectable HCV RNA at 4, 12 and 24 wk after treatment was considered as rapid virological response, complete early virological response, and sustained virological response (SVR), respectively. Biomarkers of in? ammation were measured. RESULTS: The treatment group with vitamin D hadhigher BMI (30 ± 6 vs 26 ± 3, P < 0.02), and high viral load (> 400 000 IU/mL, 65% vs 40%, P < 0.01) than controls. Ninety-fi ve percent of treated patients were HCV RNA negative at week 4 and 12. At 24 wk after treatment (SVR), 19/20 (95%) treated patients and 23/30 (77%) controls were HCV RNA negative (P < 0.001). Baseline serum vitamin D levels were lower at baseline (20 ± 8 ng/mL) and increased after 12 wk vitamin D treatment, to a mean level of (34 ± 11 ng/ mL). Logistic regression analysis identifi ed vitamin D supplement [odds ratio (OR) 3.0, 95% CI 2.0-4.9, P < 0.001], serum vitamin D levels (< 15 or > 15 ng/mL, OR 2.2, P < 0.01), and BMI (< 30 or > 30, OR 2.6, P < 0.01) as independent predictors of viral response. Adverse events were mild and typical of Peg/RBV. CONCLUSION: Low vitamin D levels predicts negative treatment outcome, and adding vitamin D to conventional Peg/RBV therapy for patients with HCV genotype 2-3 signifi cantly improves viral response.
文摘Hepatocellular carcinoma(HCC) is one of the most commonly diagnosed and deadly cancers worldwide; its incidence has been rising in the United States due to the increase in hepatitis C associated cirrhosis and the growing epidemic of obesity. There have been no effective therapeutic options in the advanced disease setting beyond sorafenib, a multi-targeted tyrosine kinase inhibitor that showed significant survival benefit. Because of this, there is an urgent need to search for novel pathways in sorafenib experienced patients. This review will focus on the role of hypoxia and hypoxiainducible factor alpha(HIF-1α) in cancer development, specifically in HCC. We will discuss the biology of HIF-1α, the pathways with which it interacts, and the function of HIF-1α in HCC. Furthermore, we will review studies highlighting the relevance of HIF-1α in the clinical setting, as well as the pre-clinical data supporting its further investigation. Finally, we will conclude with a discussion of the potential role of a HIF-1α m RNA antagonist for the treatment of HCC, and hypothesize the ways in which such an inhibitor may be best utilized in the management of advanced HCC. Hypoxia plays a significant role in the development of HCC. HIF-1α is a key transcription factor involved in the hypoxic response of cancer cells. It activates transcription of genes responsible for angiogenesis, glucose metabolism, proliferation, invasion and metastasis in HCC. Its involvement in multiple, essential tumor pathways makes it an attractive potential therapeutic target in HCC.
基金Supported by The National Natural Science Foundation of China,No.30671856,30772536 and 81072710Beijing Natural Science Foundation,No.7101006+2 种基金the state key project for infectious diseases,2008ZX10002-015,2008ZX10002-005-3Beijing Science and Technology Commission,Z111107058811067High-Level Talent Academic Leader Training Program,(2011-2-09)
文摘AIM:To investigate the biological role of alpha fetoprotein (AFP) and its clinical signif icance in carcinogenesis of hepatocellular carcinoma (HCC).METHODS:Clinical analysis of HCC patients and im-munohistochemical examination were conducted to evaluate the relationship between serum AFP level and patient mortality. Confocal microscopy,Western blotting, dimethylthiahzolyl-2,5-diphenyl-tetrazolium bromide,Cell Counting Kit-8 assays and flow cytometry were performed to explore the possible mechanism.RESULTS: Among the 160 HCC patients enrolled in this study,130 patients survived 2 years (81.25%),with a survival rate of 86.8% in AFP < 2 0 μg/L group,88.9% in AFP 20-250 μg/L group,and 69.6% in AFP > 250 μg/L group, demonstrating a higher mortality rate in HCC patients with higher AFP levels. Surgical treatment was benef icial only in patients with low AFP levels.The mortality rate of HCC patients with high AFP levels who were treated surgically was apparently higher than those treated with conservative management.The results of immunohistochemistry showed that AFP and AFP receptor were merely expressed in tissues of HCC patients with positive serum AFP.Consistently,in vitro analysis showed that AFP and AFPS were expressed in HepG2 but not in HLE cells. AFP showed a capability to promote cell growth,and this was more apparent in HepG2 cells,in which the proliferation was increased by 3.5 folds. Cell cycle analysis showed that the percent-age of HepG2 cells in S phase after exposure to AFP was modestly increased.CONCLUSION:HCC patients with higher AFP levels show a higher mortality rate,which appears to be attributable to the growth promoting properties of AFP.
基金supported by a grant from the Zhuhai Key Discipline Project of China,No.200880
文摘Lipoxin A4 can alleviate cerebral ischemia/reperfusion injury by reducing the inflammatory reaction,but it is currently unclear whether it has a protective effect on diabetes mellitus complicated by focal cerebral ischemia/reperfusion injury.In this study,we established rat models of diabetes mellitus using an intraperitoneal injection of streptozotocin.We then induced focal cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours.After administration of lipoxin A4 via the lateral ventricle,infarction volume was reduced,the expression levels of pro-inflammatory factors tumor necrosis factor alpha and nuclear factor-kappa B in the cerebral cortex were decreased,and neurological functioning was improved.These findings suggest that lipoxin A4 has strong neuroprotective effects in diabetes mellitus complicated by focal cerebral ischemia/reperfusion injury and that the underlying mechanism is related to the anti-inflammatory action of lipoxin A4.
文摘AIM To determine the tumor necrosis factor alpha (TNFα), interleukin 6 (IL 6) and soluble interleukin 2 receptor (sIL 2r) from peripheral blood mononuclear cells (PBMC) in 25 Chinese patients with ulcerative colitis and 20 healthy controls. METHODS PBMC were isolated by density gradient centrifugation of heparinized blood and cultures for 24 or 48 hours by stimulation with LPS or PHA. TNFα and sIL 2r were measured by ELISA method and IL 6 measured by bioassay. RESULTS TNFα production stimulated by LPS and sIL 2r production by PHA in ulcerative colitis were significantly lower than in healthy controls (TNFα 509(46-7244)ng/L vs 1995(117-18 950)ng/L, P <0 05; sIL 2r 320U/ml±165U/ml vs 451U/ml±247U/ml, P <0 05). Spontaneous TNFα and sIL 2r production were not significantly different between ulcerative colitis and controls (TNFα 304(46-7044)ng/L vs 215(46-4009)ng/L, P >0 05; sIL 2r 264U/ml±115U/ml vs 236U/ml±139U/ml, P >0 05). IL 6 production by spontaneous release from PBMC in ulcerative colitis group was 109U/ml±94U/ml vs 44U/ml±39U/ml for those in healthy controls, P <0 01. IL 6 stimulated by LPS in ulcerative colitis group was (261U/ml±80U/ml) higher than in healthy controls (102U/ml±54U/ml, P <0 01). No correlation of TNFα, IL 6, sIL 2r production was found to disease activity, disease location and medication. CONCLUSION Cytokine production from PBMC was also disturbed in Chinese patients with ulcerative colitis.
基金Supported by Grants-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science and Technology of Japan,to Yamamoto H and Shinomura Y
文摘AIM:To investigate human epidermal growth factor receptor 2(HER2)-phosphatidylinositol 3-kinase(PI3K)-vAkt murine thymoma viral oncogene homolog signaling pathway.METHODS:We analyzed 231 formalin-fixed,paraffinembedded gastric cancer tissue specimens from Japanese patients who had undergone surgical treatment.The patients' age,sex,tumor location,depth of invasion,pathological type,lymph node metastasis,and pathological stage were determined by a review of the medical records.Expression of HER2 was analyzed by immunohistochemistry(IHC) using the HercepTest TM kit.Standard criteria for HER2 positivity(0,1+,2+,and 3+) were used.Tumors that scored 3+ were considered HER2-positive.Expression of phospho Akt(pAkt) was also analyzed by IHC.Tumors were considered pAkt-positive when the percentage of positive tumor cells was 10% or more.PI3K,catalytic,alpha polypeptide(PIK3CA) mutations in exons 1,9 and 20 were analyzed by pyrosequencing.Epstein-Barr virus(EBV) infection was analyzed by in situ hybridization targeting EBV-encoded small RNA(EBER) with an EBER-RNA probe.Microsatellite instability(MSI) was analyzed by polymerase chain reaction using the mononucleotide markers BAT25 and BAT26.RESULTS:HER2 expression levels of 0,1+,2+ and 3+ were found in 167(72%),32(14%),12(5%) and 20(8.7%) samples,respectively.HER2 overexpression(IHC 3+) significantly correlated with intestinal histological type(15/20 vs 98 /205,P = 0.05).PIK3CA mutations were present in 20 cases(8.7%) and significantly correlated with MSI(10/20 vs 9/211,P < 0.01).The mutation frequency was high(21%) in T4 cancers and very low(6%) in T2 cancers.Mutations in exons 1,9 and 20 were detected in 5(2%),9(4%) and 7(3%) cases,respectively.Two new types of PIK3CA mutation,R88Q and R108H,were found in exon1.All PIK3CA mutations were heterozygous missense singlebase substitutions,the most common being H1047R(6/20,30%) in exon20.Eighteen cancers(8%) were EBV-positive and this positivity significantly correlated with a diffuse histological type(13/18 vs 93/198,P = 0.04).T
