卒中性脑血管病并发抑郁症105例临床分析

本文对１９９０～１９９５年收治８８８例脑血管病例进行回顾性调查，全部病人经颅ＣＴ或ＭＲＩ证实，缺血性卒中５１７例，出血性３７１例。采用Ｈａｍｉｌｔｏｎ 抑郁量表进行评估，发现抑郁症１０５例，发生率１１．７％，出血性发生率１５．１％，梗塞性发生率９．５％，二组比较ｘ２＝５．３２，Ｐ＜０．０５。显示出血性卒中并发抑郁症机率高。左侧发生率１３．４％，右侧发生率１０．１％。

Ruptured high flow gastric varices with an intratumoral arterioportal shunt treated with balloon-occluded retrograde transvenous obliteration during temporary balloon occlusion of a hepatic artery

A patient presented with hematemesis due to gastric variceal bleeding with an intratumoral arterioportal shunt. Contrast-enhanced CT revealed gastric varices and hepatocellular carcinoma with tumor thrombi in the right portal vein. Angiography and angio-CT revealed a marked intratumoral arterioportal shunt accompanied with reflux into the main portal vein and gastric varices. Balloon-occluded retrograde venography from the gastro-renal shunt showed no visualization of gastric varices due to rapid blood flow through the intratumoral arterioportal shunt. The hepatic artery was temporarily occluded with a balloon catheter to reduce the blood flow through the arterioportal shunt, and then concurrent balloon-occluded retrograde transvenous obliteration （BRTO） was achieved. Vital signs stabilized immediately thereafter, and contrast-enhanced CT revealed thrombosed gastric varices. Worsening of hepatic function was not recognized. BRTO combined with temporary occlusion of the hepatic artery is a feasible interventional procedure for ruptured high flow gastric varices with an intratumoral arterioportal shunt.

Capability of multidetector CT to diagnose hepatocellular carcinoma-associated arterioportal shunt

AIM: To investigate the capability of multidetector CT (MDCT) to diagnose HCC-associated arterioportal shunt (APS).METHODS: Two hundred and eighty-two patients with HCC received both thin-slice and enhancement MDCT scanning at early hepatic arterial phase, late hepatic arterial phase and portal venous phase, and digital subtract angiography (DSA) examination. Images were analyzed jointly by two experienced radiologists blinded to the opposite examination results, including the existence or not of APS, shunt locations, types and degrees of APS, with or without thrombosis. RESULTS: There were 56 APS associated with HCC, including 48 central, seven peripheral and one mixed, or 42 severe, seven moderate, seven mild APS. Fortyone severe, seven moderate and central APS were all revealed with MDCT and DSA. Seven mild and peripheral APS were all displayed with MDCT; only five of them displayed DSA, two faint shunt APS associated with massive HCC were missed. One mixed APS was demonstrated as severe combined with mild shunt with both MDCT and DSA.CONCLUSION: MDCT could diagnose not only DSA revealed APS, but also missed mild and peripheral APS with DSA due to faint shunt associated with massive HCC, is a simple, effective and noninvasive new technique for diagnosis of HCC-associated APS.

Functional expression of a proliferation-related ligand in hepatocellular carcinoma and its implications for neovascularization

AIM： To detect the expression of a proliferation-related ligand on human hepatocellular carcinoma （HCC） cell lines （SK-Hepl, HLE and HepG2） and in culture medium. METHODS： APRIL expression was analyzed by Western blotting in HCC cell lines. Effects of APRIL to cell count and angiogenesis were analyzed, too. RESULTS： Recombinant human APRIL （rhAPRIL） increased cell viability of HepG2 cells and, in HUVEC, rhAPRIL provided slight tolerance to cell death from serum starvation. Soluble APRIL （sAPRIL） from HLE cells increased after serum starvation, but did not change in SK-Hepl or HepG2 cells. These cells showed down-regulation of VEGF after incubation with anti-APRIL antibody. Furthermore, culture medium from the HCC cells treated with anti-APRIL antibody treatment inhibited tube formation of HUVECs. CONCLUSION： Functional expression of APRIL might contribute to neovascularization via an upregulation of VEGF in HCC.

Effect of serum concentration on adhesion of monocytic THP-1 cells onto cultured EC monolayer and EC-SMC co-culture

Background:The adhesion of monocytes to the endothelium following accumulation of low-density lipoprotein (LDL) in subendothelial spaces is an important step in the development of intimal hyperplasia in arterially implanted vein grafts and atherosclerosis in both animals and humans. However, it is not well known how serum factors affect the adhesion of monocytes. Methods: We have studied the effect of fetal calf serum (FCS), which we considered a source of LDL, on the adhesion of monocytes to endothelial cells (ECs) by using human monocytic THP-1 cells and both a monolayer of cultured bovine aortic endothelial cells (EC monoculture) and a co-culture with bovine aortic smooth muscle cells (EC-SMC co-culture). Results: It was found that the addition of FCS to the medium greatly affected the adhesion of THP-1 cells, and the higher the concentration of FCS in the medium, the greater the adhesion of THP-1 cells to endothelial cells. Adhesion of THP-1 cells to an EC-SMC co-culture was approximately twofold greater than that to an EC monoculture, and after adhering to endothelial cells, many THP-1 cells trans-migrated into the layer of smooth muscle cells. Conclusion: The results suggest that the elevation of the LDL (cholesterol) level in blood provides a favorable condition for the development of intimal hyperplasia and atherosclerosis by promoting the adhesion of monocytes to the endothelium and their subsequent migration into subendothelial spaces.

Lipomatous hemangiopericytoma of the stomach:A case report and a review of literature

Lipomatous hemangiopericytomas(LHPCs) are rare soft-tissue tumors that are histologically characterized by hemangiopericytomatous vasculature and the presence of mature adipocytes.We present the clinicopathological features of a case of gastric LHPC in a 56-year-old female,along with a literature review.Endoscopy and endoscopic ultrasound showed a submucosal tumor 0.8 cm across in the greatest dimension in the lesser curvature side of the gastric antrum.Grossly,the well-defined mass had a solid and tan-white cut surface admixed with myxoid regions and yellowish areas.Histological examination revealed a submucosal well-circumscribed lesion composed of cellular nodules with the classic appearance of an hemangiopericytoma admixed with clusters and lobules of mature adipocytes.The ill-defined tumor cells had weakly eosinophilic cytoplasm and contained spindled nuclei with occasional small nucleoli.Nuclei atypia and mitoses were absent,and no cellular atypia,necrosis or vascular invasion was observed.Immunohistochemistry showed that the tumor cells were diffusely positive for CD34,CD99,and vimentin and were focally reactive for bcl-2.This is the first known report of an LHPC in the stomach.The patient was followed for 12 mo without any evidence of metastasis or recurrence.

Littoral-cell angioma of the spleen:a case report

Littoral-cell angioma(LCA), a primary angioma which clinically belongs to splenic hemangioma, can be mostly found in normal spleen red sinus shore cells of reticuloendothelial cell system. The cells of LCA strongly express endothelial and tissue cell associated antigens that indicate a dual differentiation characteristic; whereas only endothelial cell markers are positive in normal spleen red sinus shore cells. Diagnosis of LCA relies on histopathology. Regular follow-up is needed to monitor recurrence and metastasis.

REAL-TIME THREE-DIMENSIONAL ECHOCARDIOGRAPHY FOR QUANTIFYING LEFT VENTRICULAR MASS

To test the accuracy of real-time three-dimensional echocardiography (RT3DE) imaging system for evaluating left ventricular mass (LVM) in phantom and excised canine heart. Methods Ten left ventricular (LV) wall phantoms made of two rubber-bursas, ten excised canine hearts underwent RT3DE and two-dimensional echocardiography (2DE). In RT3DE "full volume" imaging, the myocardial volume was mea-sured using 2,4,8, and 16-plane method with the analysis software of RT3DE. Mass was then calculated by multiplying the resulting myocardial volume by specific density of myocardial tissue. In 2DE the masses were measured by area-length meth-od. The true LV wall phantom mass was measured by water displacement and the canine LVM was weighed by anatomy, which served as a reference standard. We compared RT3DE or 2DE with true mass. Results In LV wall phantoms, RT3DE correlated with true masses strongly (r = 0.813-0.994) and weakly correlated between 2DE and true masses (r = 0.628). In excised canine hearts, there is an excellent correlation between RT3DE and true masses (r = 0.764-0.991), while 2DE value showed a lesser correlation (r = 0.514). There are no difference between RT-3DE and true masses (P > 0.05) but different between 2DE and true masses (P < 0.05). In different planes, there was no difference between 8-plane and 16-plane (P > 0.05) but different between 8-plane and 2, 4-plane (P < 0.05). Conclusion RT3DE can accurately quantify LVM and provide a new tool to evaluate LV function. For LVM by RT3DE, 8-plane measurement method is the best choice for accuracy and convenience.

Relationship between P-glycoprotein and CD44 expression in esophageal carcinoma

Objective： To investigate the relationship between P-glycoprotein （P-gp） and adhesion molecule CD44 expression as well as their clinical significance in esophageal carcinoma. Methods： To examine the expressed level of P-gp and CD44 by flow cytometry （FCM） in the operated samples of 70 cases with esophageal carcinoma and their normal mucosa of esophageal incision, and to evaluate their relationship with clinicopathological factors. Results： Among the 70 cases with esophageal carcinoma, the expression of P-gp in the 27 cases （38.6%） was negative （positive cells 〈25%）; 11 cases （15.7%） were 25%-40% expression of P-gp positive cells; 14 cases （20%） were 41%-60% expression of P-gp positive cells; 18 cases （25.7%） were the high expression （positive cells 〉60%） of P-gp. Of the cases with the tumor sizes being more than 4 cm, the expression of CD44 showed a significant difference （P〈0.05） in 25 cases with P-gp positive, compared with 19 cases with P-gp negative. Of the cases with high-mild differentiated esophageal carcinoma, the expression of CD44 showed a significant difference （P〈0.05） in 22 cases with P-gp positive, compared with 17 cases with P-gp negative. Of the cases with clinical Ⅲ-Ⅳ stage, the expression of CD44 showed a significant difference （P〈0.05） in 26 cases with P-gp positive, compared with 10 cases with P-gp negative. Of the cases with lymph node metastasis, the CD44 expression showed a significant difference （P=0.050） in 27 cases with P-gp positive, compared with 11 cases with P-gp negative. Of the cases of the patients＇ age being more than 56 years, the expression of CD44 showed a significant difference （P〈0.01） in 27 cases with P-gp positive, compared with 12 cases with P-gp negative. When the P-gp and CD44 expression were positive, the clinical Ⅱ stage and Ⅲ-Ⅳ stage in esophageal carcinoma was showed a significant difference （P〈0.05）. Conclusion： When the CD44 and P-gp both have the positive high expression, it will be significantly associated with the esophageal carcinoma progression and metastasis, so both were a positive expression in esophageal carcinoma, it might suggest a poor and unfavorable prognosis result.

Immortalization of human umbilical vein endothelial cells with telomerase reverse transcriptase and simian virus 40 large T antigen

Objective: To establish normally conditionally-immortalized human umbilical vein endothelial cells (HUVECs) by ectopic expression of the human telomerase catalytic enzyme (hTERT) and simian virus 40 large T (SV40 LT) antigen. Methods:Primary HUVECs were transfected with recombinant retrovirus containing hTERT or SV40 LT respectively. Subsequently drug resistant cell clones were screened and expanded for further studies. Endothelial cell biomarkers were confirmed by examination.Results: The morphological phenotype of the transfected cells was similar to the non-transfected cells. Von Willebrand factor,hTERT and SV40 LT could be detected in transfected HUVECs. Moreover, higher telomerase activity in transfected cells was maintained for over 50 population doublings compared with only low level of endogenous telomerase transiently at early population doublings in primary HUVECs. When exposed to TNF-α (tumor necrosis factor-α), the expression of E-selectin in transfected cells was significantly up-regulated, but no alteration of endothelial lipase was found. Conclusion: Ectopic coexpression of hTERT and SV40 LT can effectively immortalize HUVECs without tumorigenicity in vitro. Immortalized HUVECs may be an ideal target of further molecular function studies.

The apoptosis in various stages of infantile hemangioma

Objective: To detect the apoptosis in various stages of infantile hemangioma. Methods:Total 52 samples of infantile hemangioma (including 8 fresh samples) were included in this study. Agarose gel electrophoresis, transmission electron microscopy(TEM) and in situ TdT mediated dUTP-biotin nick end labeling(TUNEL) staining were used to observe the apoptosis. H-E staining was used to analyze the number of cells,the number and area of microvessels in hemangiomas. Results: The typical “ladder” occurred in the DNA electrophoresis of the hemangioma tissue in the late proferating stage. Many apoptotic cells were found in infantile hemangiomas with TEM. TUNEL staining identified that there were apoptotic cells througout the pathologic evolution of infantile hemangioma and the AI(%) was the highest in the late proferating stage. There existed close relationship between the AI(%) and the total number of cells in hemangioma. Conclusion: The decrease of cells resulted from the apoptosis may be the major cause of the spontaneous involution of infantile hemangioma.

VEGI-armed oncolytic adenovirus inhibits tumor neovascularization and directly induces mitochondria-mediated cancer cell apoptosis

Vascular endothelial cell growth inhibitor （VEGI） is a member of the tumor necrosis factor superfamily and plays an important role in vascular homeostasis. In this study, to investigate the anticancer therapeutic potential of this gene, a secreted isoform of VEGI （VEGI-251） was inserted into a selectively replicating adenovirus with E1B 55 kDa gene deletion （ZD55） to construct ZD55-VEGI-251. We report here that secreted VEGI-251 produced from ZD55- VEGI-251-infected cancer cells potently inhibits endothelial cell proliferation, tube formation in vitro and angiogen- esis of chick chorioallantoic membrane in vivo. Additionally, ZD55-VEGI-251 infection leads to a much more severe cytopathic effect than control viruses on several human cancer cell lines, including cervical cancer cell line HeLa, hepatoma cell line SMMC-7721 and colorectal cancer cell line SW620. Further study reveals that the increased cytotoxicity is a result of VEGI-251 autocrine-dependent, mitochondria-mediated apoptosis accompanied by caspase-9 activation, enhanced caspase-3 activation and PARP cleavage. Moreover, ZD55-VEGI-251-treatment of athymic nude mice bearing human cervical and colorectal tumor xenografts markedly suppressed tumor growth. Our findings indicate that the combined effect of antiangiogenesis and apoptosis-induction activity makes the VEGI-251-armed oncolytic adenovirus a promising therapeutic agent for cancer.

SARS coronavirus entry into host cells through a novel clathrin- and caveolae-independent endocytic pathway

While severe acute respiratory syndrome coronavirus （SARS-CoV）~as initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that yirus entry may also involve endocytosis. We have found that SARS-CoV enters cells viapH- and receptor-dependent endocytosis. Treatment of cells with either SARS-COV spike protein or spike-bearing pseudoviruses resulted in the translocation of angiotensin-converting enzyme 2 （ACE2）, the functional receptor of SARS-CoV, from the cell surface to endosomes. In addition, the spike-bearing pseudoviruses and early endosome antigen 1 were found to colocalize in endosomes. Further analyses using specific endocytic path- way inhibitors and dominant-negative Epsl5 as well as caveolin-1 colocalization study suggested that virus entry was mediated by a clathrin- and caveolae-independent mechanism. Moreover, cholesterol- and sphingolipid-rich lipid raft microdomains in the plasma membrane, which have been shown to act as platforms for many physiological signaling pathways, were shown to be involved in virus entry. Endocytic entry of SARS-CoV may expand the cellular range of SARS-CoV infection, and our findings here contribute to the understanding of SARS-CoV pathogenesis, providing new information for anti-viral drug research.

Significant roles of anti-aging protein klotho and fibroblast growth factor23 in cardiovascular disease

The klotho gene has been identified as an aging suppressor that encodes a protein involved in cardiovascular disease （CVD）. The inac- tivation of the klotho gene causes serious systemic disorders resembling human aging, such as atherosderosis, diffuse vascular calcification and shortened life span. Klotho has been demonstrated to ameliorate vascular endothelial dysfunction and delay vascular calcification. Fur- thermore, klotho gene polymorphisms in the human are associated with various cardiovascular events. Recent experiments show that klotho may reduce transient receptor potential canonical6 （TRPC6） channels, resulting in protecting the heart from hypertrophy and systolic dys- function. Fibroblast growth factor23 （FGF23） is a bone-derived hormone that plays an important role in the regulation of phosphate and vi- tamin D metabolism. FGF23 accelerates urinary phosphate excretion and suppresses 1,25-dihydroxy vitaminD3 （1,25（OH）2D3）synthesis in the presence ofFGF receptorl （FGFR1） and its co-receptor ldotho, principally in the kidney. The hormonal affects of circulating klotho pro- tein and FGF23 on vascular and heart have contributed to an understanding of their roles in the pathophysiology of arterial stiffness and left ventricular hypertrophy. Klotho and FGF23 appear to play a critical role in the pathogenesis of vascular disease, and may represent a novel potential therapeutic strategy for clinical intervention.

Clinicopathological and Genetic Study of an Atypical Renal Hemangioblastoma

HEMANGIOBLASTOMA（HB）,a kind of benign tumor with uncertain histogenesis,is Characterized by the presence of stromal cells（SCs）and a rich vascular component.1 It occurs sporadi cally,

The correlation and relationship of obesity and cancer: a possible research perspective

Recently, obesity is a well-recognized risk factor of type 2 diabetes and cardiovascular disease. There is more and more sufficient evidence that excess body weight is an avoidable cause of excess cancers including gastrointestinal, endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal cancers. The mechanism that obesity association with cancer is remains not well understood. There be some most studied hypothesized mechanisms such as, high levels of insulin and free levels of insulin-like growth factors （IGFs）, sex hormones, adipocytokines, intlammatory cytokines, c-Myc （or Myc） oncogenic transcription factor, obesity-induced hypoxia and Warburg effect, and so on. In the future, the potential mechanisms and conclusions in obesity associated with increased risk for developing cancer, and the underlying cellular and molecular mechanisms will be studied.

Littoral-cell angioma of the spleen:A case report

Littoral-cell angioma （LCA） is a primary splenic vascular tumor that arises from the normal littoral cells lining the sinus channels of the splenic red pulp. We report a case of LCA of the spleen, which has been infrequently communicated in the literature. A 76-year-old man with a 2-wk history of weight loss, abdominal pain and changes in bowel habits was admitted to our hospital. Imaging studies （CT and MR1） showed multiple lesions in the spleen. Splenectomy was performed. Lining cells were positive for CD31/CD68 markers. Our case was associated with a serrated colonic adenoma. LCA is a benign vascular tumor of the spleen that needs to be included in the differential diagnosis of multiple splenic nodules.

VEGF in hepatocellular carcinoma and surrounding cirrhotic liver tissues

We read with a great interest the recent work of Deli and colleagues. in the World Journal of Gastroenterology reporting vascular endothelial growth factor （VEGF） expression in hepatocellular carcinoma （HCC） and cirrhotic liver tissues. This well-documented work shows that VEGF was significantly higher in surrounding cirrhotic liver tissues than in HCC. Authors assessed VEGF expression using immunohistochemistry. The immunohistochemical staining is an efficient tool to assess the percentage of cells stained positively for VEGF but is not really efficient to estimate their true VEGF content. Evaluation of the VEGF protein by an enzyme-linked immunosorbent assay 0ELISA） has been reported, by us and others, to be an efficient tool in order to assess tissue VEGF expression. We have, thus, tested whether the ELISA method might be an efficient tool in order to confirm data reporting higher amounts of VEGF in surrounding cirrhotic liver tissues than in HCC. Deli and colleagues. also correctly pointed out that basic fibroblast growth factor （bFGF） has been reported to act cooperatively on VEGF expression. We have, thus, also assessed bFGF tissue levels in order to search for a putative link between VEGF and bFGF levels in cirrhotic tissues.

Clopidogrel and proton pump inhibitors-where do we stand in 2012?

Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events.Concomitant treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical guidelines.Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19(CYP2C19) and proton pump inhibitors(PPIs) are extensively metabolized by the CYP2C19 isoenzyme as well.Several pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole,but not for pantoprazole.Initial clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events,when under clopidogrel and PPI treatment at the same time.These observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI(especially omeprazole) in the same year.In contrast,more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on clopidogrel.Three meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality,with high and moderate quality studies not reporting any association,rising concern about unmeasured confounders biasing the low quality studies.Thus,no definite evidence exists for an effect on mortality.Because PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding,combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended.

What's hot in inflammatory bowel disease in 2011?

Ulcerative colitis and Crohn's disease(CD) are the two major forms of inflammatory bowel disease(IBD).In this highlight topic series of articles,the most recent advances in the IBD field are reviewed,especially the newly described cytokines,including the therapeutic implications for their manipulation.In addition,the interplay between the intestinal microbiota and the host is reviewed,including the role of defensins and dysbiosis in CD pathogenesis.Finally,the importance of the non immune systems such as endothelial cells and the hemostatic system are highlighted as new players in IBD pathogenesis.