Evaluation of large language models in breast cancer clinical scenarios: a comparative analysis based on ChatGPT-3.5, ChatGPT-4.0, and Claude2.

BACKGROUND: Large language models (LLMs) have garnered significant attention in the AI domain owing to their exemplary context recognition and response capabilities. However, the potential of LLMs in specific clinical scenarios, particularly in breast cancer diagnosis, treatment, and care, has not been fully explored. This study aimed to compare the performances of three major LLMs in the clinical context of breast cancer. METHODS: In this study, clinical scenarios designed specifically for breast cancer were segmented into five pivotal domains (nine cases): assessment and diagnosis, treatment decision-making, postoperative care, psychosocial support, and prognosis and rehabilitation. The LLMs were used to generate feedback for various queries related to these domains. For each scenario, a panel of five breast cancer specialists, each with over a decade of experience, evaluated the feedback from LLMs. They assessed feedback concerning LLMs in terms of their quality, relevance, and applicability. RESULTS: There was a moderate level of agreement among the raters (Fleiss' kappa=0.345, P<0.05). Comparing the performance of different models regarding response length, GPT-4.0 and GPT-3.5 provided relatively longer feedback than Claude2. Furthermore, across the nine case analyses, GPT-4.0 significantly outperformed the other two models in average quality, relevance, and applicability. Within the five clinical areas, GPT-4.0 markedly surpassed GPT-3.5 in the quality of the other four areas and scored higher than Claude2 in tasks related to psychosocial support and treatment decision-making. CONCLUSION: This study revealed that in the realm of clinical applications for breast cancer, GPT-4.0 showcases not only superiority in terms of quality and relevance but also demonstrates exceptional capability in applicability, especially when compared to GPT-3.5. Relative to Claude2, GPT-4.0 holds advantages in specific domains. With the expanding use of LLMs in the clinical field, ongoing optimization and rigorous accuracy assessments are paramount.

Guajadial reverses multidrug resistance by inhibiting ABC transporter expression and suppressing the PI3K/Akt pathway in drug-resistant breast cancer cells.

Multidrug resistance remains a major challenge in the chemotherapy of breast cancer. Guajadial, a natural meroterpenoid, has been found to possess anti-tumor activity. However, the role of guajadial in drug resistance has not been investigated. The aim of this study was to evaluate the effect of guajadial on drug resistance in drug-resistant breast cancer cells. Cell viability was measured by MTT assay, and the IC50 values were calculated. The expression of ATP-binding cassette (ABC) transporters including P-glycoprotein (P-gp) and the breast cancer resistance protein (BCRP) was detected by qRT-PCR and western blot. The expression of Akt, p-Akt, p70S6K, and p-p70S6K was determined by western blot. We found that guajadial significantly inhibited cell viability of parental non-resistant cell line MCF-7, adriamycin (ADR)-resistant cell line MCF-7/ADR, and paclitaxel (PTX)-resistant cell line MCF-7/PTX in a dose-dependent manner. Guajadial enhanced ADR and PTX sensitivity of MCF-7/ADR and MCF-7/PTX cells, and inhibited the expression of P-gp and BCRP. Guajadial treatment resulted in an inactivation of PI3K/Akt pathway in drug-resistant MCF-7 cells. In conclusion, guajadial acted as an inhibitor of drug resistance, which might be mediated by the inhibition of ABC transporter expression and PI3K/Akt pathway in drug-resistant breast cancer cells. These findings suggested that guajadial treatment might be a new approach to overcome the drug resistance in the chemotherapy of breast cancer.

Epithelial­mesenchymal transition induced by bone morphogenetic protein 9 hinders cisplatin efficacy in ovarian cancer cells.

Bone morphogenetic protein 9 (BMP9) belongs to the transforming growth factor­ß (TGF­ß) superfamily, and has been reported to promote cancer cell proliferation and epithelial­mesenchymal transition (EMT). Cisplatin (DDP) is the first line treatment for ovarian cancer. However, initiation of EMT confers insensitivity to chemotherapy. The present study aimed to verify and examine the mechanisms underlying the effects of BMP9 on treatment with DDP for ovarian cancer. Prior to treatment with DDP, ovarian cancer cells were exposed to BMP9 for 3 days. Following this, cell viability, apoptosis rate and the extent of DNA damage were evaluated to compare the effects of DDP on BMP9­pretreated and non­pretreated ovarian cancer cells. In addition, EMT marker expression was evaluated by western blotting and immunofluorescence. The results demonstrated that BMP9 pretreatment inhibited the cytotoxicity of DDP on ovarian cancer cells. Additionally, BMP9­pretreated ovarian cancer cells had downregulated expression of the epithelial marker E­cadherin, which was accompanied by an upregulation of the mesenchymal markers N­cadherin, Snail, Slug, and Twist. Taken together, the findings of the present study indicated that BMP9 conferred resistance to DDP in ovarian cancer cells by inducing EMT. The present study provided valuable insight into the mechanisms of chemotherapy in ovarian cancer and highlighted the potential of BMP9 as a novel therapeutic target for improving cisplatin chemosensitivity.

Bcl-2-associated athanogene 3(BAG3) is associated with tumor cell proliferation, migration, invasion and chemoresistance in colorectal cancer.

BACKGROUND: CRC is one of the most common malignancies worldwide, and its molecular mechanisms remain unclear. Elevated levels of BAG3 have been reported in various tumors. The present study aimed to explore the expression and function of BAG3 in CRC. METHODS: BAG3 protein expression was evaluated in 90 CRC specimens using immunohistochemistry in tissue microarrays, and the correlation between BAG3 expression and the clinicopathological features were assessed. In HCT116 cells BAG3 overexpression cell models were constructed, and CRISPR/Cas9 was used for BAG3 knockout. Western blotting and quantitative real-time PCR were used to determine BAG3 expression in HCT-116 Cells. Cell proliferation, migration and invasion were analyzed by cell counting, colony formation assay, EdU cell proliferation assay, RTCA growth curve assays, wound-healing migration assay and transwell invasion assay. The influence of BAG3 expression level on chemoresistance in HCT-116 cells was examined. Gene expression microarray and IPA analyses were employed to explore signaling pathways associated with the control of BAG3. RESULTS: Using immunohistochemistry, this study found that BAG3 was markedly upregulated in colorectal cancer tissues and that BAG3 levels were significantly associated with tumor size and gender. BAG3 overexpression promoted HCT-116 cell growth, migration and invasion in vitro. In contrast, BAG3 knockout inhibited HCT-116 cell growth, migration and invasion. HCT-116 cells with high expression of BAG3 had higher cell viability and lower apoptosis rate than control cells after treatment with 5-FU, while the BAG3 knockout group demonstrated the opposite effects. So BAG3 expression level was associated with chemoresistance to 5-FU in HCT-116 cells. Gene expression microarrays and bioinformatics analyses of HCT-116 cells with BAG3 knockout demonstrated the involvement of BAG3 in signaling pathways associated with the control of cell proliferation, migration, invasion and chemoresistance in CRC. CONCLUSIONS: In conclusion, this study provided evidence that BAG3 has a relevant role in CRC biology, and defined potential molecular pathways and networks. So BAG3 may be considered as a potential therapeutic target for anti-tumor therapy in colorectal cancer.

ß-catenin, leucine-rich repeat-containing G protein-coupled receptor 5 and GATA-binding factor 6 are associated with the normal mucosa-adenoma-adenocarcinoma sequence of colorectal tumorigenesis.

In the present study, the expression of ß-catenin, leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) and GATA6 was investigated during the transition from normal mucosa through to adenoma and adenocarcinoma in colorectal tissue sections obtained from 65 patients with a pathological diagnosis of colorectal adenocarcinoma and a history of adenoma. Immunohistochemical staining of ß-catenin, LGR5 and GATA6 was performed and evaluated. The nuclear expression of ß-catenin and the cytoplasmic expression of LGR5 and GATA6 were increased in samples as they progressed from normal mucosa to adenoma and adenocarcinoma. However, membrane-bound ß-catenin and nuclear GATA6 expression decreased. Positive correlations were observed between the expression of LGR5 and cytoplasmic GATA6 in adenoma (P=0.0005; rs=0.48) and adenocarcinoma samples (P=0.007; rs=0.38): However, no significant association was observed in normal mucosa (P=0.399). The expression of nuclear ß-catenin was significantly increased in the serosal layer compared with the invasive layers of the colorectal wall in samples of adenocarcinoma (P=0.042). The results of the present study suggest that the nuclear expression of ß-catenin and LGR5 and the cytoplasmic expression of GATA6 function together during the development of colorectal carcinoma.

Proteasome Inhibitor Carbobenzoxy-L-Leucyl-L-Leucyl-L-Leucinal (MG132) Enhances Therapeutic Effect of Paclitaxel on Breast Cancer by Inhibiting Nuclear Factor (NF)-κB Signaling.

BACKGROUND Carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG132), a peptide aldehyde proteasome inhibitor, can inhibit tumor progression by inactivating nuclear factor (NF)-κB signaling. Paclitaxel (PTX) is part of a routine regimen for the treatment of breast cancer. However, activation of the NF-κB pathway after treatment with PTX confers insensitivity to this drug. This study investigated the potential effect of MG132 as a co-treatment with PTX against breast cancer, and clarifies the underlying molecular mechanisms. MATERIAL AND METHODS Breast cancer cells were treated with PTX, MG132, or PTX plus MG132, and the therapeutic effects were evaluated phenotypically. A mouse model of breast cancer was used to determine the combined effect of PTX plus MG132 in vivo. RESULTS Treatment with PTX plus MG132 suppressed aggressive phenotypes of breast cancer cells more effectively than PTX alone. Consistently, MG132 also enhanced the suppressive effect of PTX on tumor growth in C57BL/6 mice. Significantly, activation of the NF-κB pathway by PTX was attenuated by MG132. CONCLUSIONS Based on our findings, we suggest the application of MG132 in clinical practice in combination with PTX for the treatment of breast cancer.

The emerging role of exosome-derived non-coding RNAs in cancer biology.

Exosomes are a new means of intercellular information exchange that have aroused great research interest. Long neglected in research, exosomes were deemed nonfunctional cellular components to be discarded. However, it has been gradually revealed that exosomes are an important tool for the exchange of intercellular information and material. Exosomes contain specific repertoires of non-coding RNAs (ncRNAs, including microRNA and lncRNA), indicating that a specific RNA sorting mechanism may exist. Correspondingly, intracellular multivesicular bodies (MVBs) are produced after fusion with the cell membrane to release exosomes rather than inducing autophagy, which reveals that there may be a specific regulatory mechanism for MVB secretion. Cells can trigger cancer-related disorders after the recognition and uptake of circulating exosomal ncRNAs, providing indications for early tumor biopsy and treatment. The use of exosomes as a biological carrier in targeted therapy has been demonstrated. However, there may be a specific, unknown switch for loading drugs. This review focuses on the mechanisms of exosome biogenesis, release, and uptake. We also review the promotion of tumor development by exosomal ncRNAs including chemotherapy resistance, metastasis and the prospective use of exosomes in cancer diagnosis and treatment.

Transforming growth factor-ß1 contributes to oxaliplatin resistance in colorectal cancer via epithelial to mesenchymal transition.

Transforming growth factor-ß1 (TGF-ß1), secreted by main components of tumor microenvironment, is considered to be closely associated with cancer development and chemoresistance. The present study aimed to analyze the effects and mechanisms underlying TGF-ß1-induced chemoresistance to oxaliplatin (LOH) in human colorectal cancer (CRC) cell lines. The cytotoxic effects of LOH subsequent to TGF-ß1 treatment were assessed in three CRC cell lines by MTT assay. In addition, epithelial to mesenchymal transition (EMT), DNA damage and apoptosis assays were performed to evaluate the mechanisms of drug resistance in vitro. It was revealed that an exposure of CRC cells to TGF-ß1 induced EMT. This was followed by a decrease in the levels of DNA damage and LOH-induced apoptotic cell death at certain TGF-ß1 concentrations compared with untreated cells, which was responsible for LOH resistance. TGF-ß1 leads to resistance to LOH in CRC cells, primarily through EMT. These data not only provide insight into the understanding of the chemoresistant mechanisms, but also may guide the clinical applications of reducing EMT to enhance the sensitivity to chemotherapy, by targeting TGF-ß1.

Colorectal cancer heterogeneity and targeted therapy: Clinical implications, challenges and solutions for treatment resistance.

Precision medicine is becoming considerably critical in colorectal cancer therapy. Particularly for targeted therapies, the response to anti-EGFR therapy largely varies among individual patients. The mechanisms of anti-EGFR-based regimens resistance have been revealed, for instance, mutations in KRAS, BRAF, and PIK3CA. It is well known that colorectal cancer is a heterogeneous disease, massive evidences indicate that there are intertumour and intratumour heterogeneities in colorectal cancer. Recently, the integrative factor of the genetic, epigenetic and microenvironmental alterations that attribute to CRC heterogeneity is associated with the response to targeted therapies. We review here the possible mechanisms of heterogeneity that influence the anti-EGFR therapy, and mainly focus on the enhancive biomarkers detection to predict the therapy efficiency and select appropriate patients who are most likely to benefit from special targeted therapies, and take advantage of simultaneously blocked the multiple molecules involved in activation of independent of ligands induced EGFR signaling pathway to overcome the resistance to anti-EGFR therapies.

Pre-treatment mean platelet volume associates with worse clinicopathologic features and prognosis of patients with invasive breast cancer.

BACKGROUND: Mean platelet volume (MPV) is one of the four platelet parameters (platelet count, MPV, platelet distribution width and plateletcrit), which indicates the activation of platelet. We aim to investigate the associations between pre-treatment MPV levels and clinical hematology parameters, pathology parameters and prognosis of patients with invasive breast cancer (IBC). METHODS: Medical records of 340 breast tumor patients (170 IBC vs. 170 breast benign tumor) were retrospectively reviewed. Patients in two groups were matched for age, body mass index, smoking status and complications. To analyze: differences in pre-treatment MPV levels between IBC group and breast benign tumor group; differences between pre- and postoperative MPV levels in IBC patients; correlations between pre-treatment MPV and clinical hematology parameters, clinicopathologic parameters and prognosis in IBC patients. RESULTS: As we analyzed, pre-treatment MPV levels of IBC patients were significantly higher than the controls (8.65 ± 0.98 vs 8.34 ± 0.78, P = 0.002), and preoperative MPV levels were significantly higher than the postoperative in IBC patients (8.65 ± 0.98 vs 8.44 ± 0.91, P = 0.042). In IBC group, pre-treatment MPV level associated, significantly, with clinical hematology parameters (platelet, fibrinogen, albumin, fasting blood glucose, P = 0.003, 0.042, 0.032, 0.046, respectively) and with clinicopathological parameters (distant metastasis, primary tumor size, tumor node metastasis stages, P = 0.039, 0.002, 0.001, respectively). Furthermore, univariate and multivariate survival analysis demonstrated that MPV was significant prognostic factor (P = 0.035, HR 1.86, 95 % confidence interval 1.06-3.25). CONCLUSION: High pre-treatment MPV level in IBC patients was a potential predictive factor and significant independent prognostic factor.

Puerarin Inhibits oxLDL-Induced Macrophage Activation and Foam Cell Formation in Human THP1 Macrophage.

Puerarin, an isoflavone derived from Kudzu roots, has been widely used for treatment of cardiovascular and cerebral vascular diseases in China and other Asian countries. However, the underlying mechanisms are largely unknown. The present study investigated whether puerarin inhibited atherogenic lipid oxLDL-mediated macrophage activation and foam cell formation in human THP1 macrophage. Treatment with oxLDL significantly increased the mRNA expression of proinflammatory cytokines tumor necrosis factor α (TNFα, 160%) and interleukin (IL) 1ß (13 fold) accompanied by upregulation of toll-like receptor 4 (TLR4, 165%) and the ratio of phospho-IκBα/IκBα in THP1 macrophage. Puerarin dose-dependently prevented an increase in oxLDL-induced proinflammatory gene expression with downregulation of TLR4 and the ratio of phospho-IκBα/IκBα. Furthermore, puerarin prevented oxLDL-mediated lipid deposition and foam cell formation associated with downregulation of scavenger receptor CD36. Flow cytometry analysis showed that puerarin reduced the number of early apoptotic cells of macrophages induced by oxLDL. Our results show that puerarin has anti-inflammatory and antiatherogenic effects in vitro; the underlying mechanisms may involve the inhibition of TLR4/NFκB pathway and downregulation of CD36 expression. The results from the present study provide scientific evidence and may expand our armamentarium to use puerarin for prevention and treatment of cardiovascular and atherosclerotic diseases.

CD105 promotes hepatocarcinoma cell invasion and metastasis through VEGF.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related morbidity and mortality. Tumor neovascularization is necessarily required for tumor progression and metastasis. CD105 and vascular endothelial growth factor (VEGF) have separately been identified as important contributors to angiogenesis; however, it is unclear if these factors interact to promote the progression of HCC. The goal of this study was to determine the interaction between CD105 and VEGF in HCC, using HCC tissue samples and the human HCC cell line SMMC-7721. In a survey of 89 HCC tumor samples, we determined that CD105 and VEGF expressions were positively correlated with each other and expressed at a higher level in tumor cells. Furthermore, the expression of CD105 was closely related to the tumor-node-metastasis (TNM) staging of HCC, degree of tumor differentiation, portal vein invasion, and lymph node metastasis (P < 0.05). Next, we used a lentiviral system to stably overexpress CD105 in SMMC-7721 cells, which was confirmed at the messenger RNA (mRNA) and protein level. We observed that VEGF expression was increased in these cells, as was cell motility and migration, as assessed using a wound healing assay and Transwell chamber system, respectively. Using VEGF small interfering RNA (siRNA), we also demonstrated that elevated VEGF expression is required to promote increased cell motility and migration in CD105-overexpressing cells. In conclusion, we interpret our data to prove that CD105 promotes the invasion and metastases of liver cancer cells by increasing VEGF expression. These results provide a new theoretical and experimental basis for the treatment of liver cancer.

Endothelial depletion of Acvrl1 in mice leads to arteriovenous malformations associated with reduced endoglin expression.

Rare inherited cardiovascular diseases are frequently caused by mutations in genes that are essential for the formation and/or function of the cardiovasculature. Hereditary Haemorrhagic Telangiectasia is a familial disease of this type. The majority of patients carry mutations in either Endoglin (ENG) or ACVRL1 (also known as ALK1) genes, and the disease is characterized by arteriovenous malformations and persistent haemorrhage. ENG and ACVRL1 encode receptors for the TGFß superfamily of ligands, that are essential for angiogenesis in early development but their roles are not fully understood. Our goal was to examine the role of Acvrl1 in vascular endothelial cells during vascular development and to determine whether loss of endothelial Acvrl1 leads to arteriovenous malformations. Acvrl1 was depleted in endothelial cells either in early postnatal life or in adult mice. Using the neonatal retinal plexus to examine angiogenesis, we observed that loss of endothelial Acvrl1 led to venous enlargement, vascular hyperbranching and arteriovenous malformations. These phenotypes were associated with loss of arterial Jag1 expression, decreased pSmad1/5/8 activity and increased endothelial cell proliferation. We found that Endoglin was markedly down-regulated in Acvrl1-depleted ECs showing endoglin expression to be downstream of Acvrl1 signalling in vivo. Endothelial-specific depletion of Acvrl1 in pups also led to pulmonary haemorrhage, but in adult mice resulted in caecal haemorrhage and fatal anaemia. We conclude that during development, endothelial Acvrl1 plays an essential role to regulate endothelial cell proliferation and arterial identity during angiogenesis, whilst in adult life endothelial Acvrl1 is required to maintain vascular integrity.

LRG1 promotes angiogenesis by modulating endothelial TGF-ß signalling.

Aberrant neovascularization contributes to diseases such as cancer, blindness and atherosclerosis, and is the consequence of inappropriate angiogenic signalling. Although many regulators of pathogenic angiogenesis have been identified, our understanding of this process is incomplete. Here we explore the transcriptome of retinal microvessels isolated from mouse models of retinal disease that exhibit vascular pathology, and uncover an upregulated gene, leucine-rich alpha-2-glycoprotein 1 (Lrg1), of previously unknown function. We show that in the presence of transforming growth factor-ß1 (TGF-ß1), LRG1 is mitogenic to endothelial cells and promotes angiogenesis. Mice lacking Lrg1 develop a mild retinal vascular phenotype but exhibit a significant reduction in pathological ocular angiogenesis. LRG1 binds directly to the TGF-ß accessory receptor endoglin, which, in the presence of TGF-ß1, results in promotion of the pro-angiogenic Smad1/5/8 signalling pathway. LRG1 antibody blockade inhibits this switch and attenuates angiogenesis. These studies reveal a new regulator of angiogenesis that mediates its effect by modulating TGF-ß signalling.

Deficiency for endoglin in tumor vasculature weakens the endothelial barrier to metastatic dissemination.

Therapy-induced resistance remains a significant hurdle to achieve long-lasting responses and cures in cancer patients. We investigated the long-term consequences of genetically impaired angiogenesis by engineering multiple tumor models deprived of endoglin, a co-receptor for TGF-ß in endothelial cells actively engaged in angiogenesis. Tumors from endoglin-deficient mice adapted to the weakened angiogenic response, and refractoriness to diminished endoglin signaling was accompanied by increased metastatic capability. Mechanistic studies in multiple mouse models of cancer revealed that deficiency for endoglin resulted in a tumor vasculature that displayed hallmarks of endothelial-to-mesenchymal transition, a process of previously unknown significance in cancer biology, but shown by us to be associated with a reduced capacity of the vasculature to avert tumor cell intra- and extravasation. Nevertheless, tumors deprived of endoglin exhibited a delayed onset of resistance to anti-VEGF (vascular endothelial growth factor) agents, illustrating the therapeutic utility of combinatorial targeting of multiple angiogenic pathways for the treatment of cancer.

[Changes of bacterial community structure on reusing domestic sewage of Daoxianghujing Hotel to landscape water].

A 16S rDNA library was used to evaluate the bacterial diversity and identify dominant groups of bacteria in different treatment pools in the domestic sewage system of the Beijing Daoxianghujing Hotel. The results revealed that there were many types of bacteria in the hotel domestic sewage, and the bacterial Shannon-Weaver diversity index was 3.12. In addition, epsilon Proteobacteria was found to be the dominant group with the ratio of 32%. In addition, both the CFB phylum, Fusobacteria, gamma Proteobacteria and Firmicutes were also reached to 9%-15%. After treated with the reclaimed water station, the bacterial Shannon-Weaver diversity index was reduced to 2. 41 and beta Proteobacteria became the dominant group and occupied 73% of the total clones. However, following artificial wetland training, the bacterial Shannon-Weaver diversity index in the sample increased to 3.38, Actinobacteria arrived to 33% and became the most dominant group; Cyanobacteria reached to 26%, and was the second dominant group. But, the control sample comprised 38% Cyanobacteria, and mainly involved in Cyanobium, Synechoccus and Microcystis, with ratios of 47.1%, 17.6% and 8.8%, respectively. Some bacteria of Microcystis aenruginosa were also detected, which probably resulted in the light bloom finally. Therefore, the bacterial diversity and community structures changed in response to treatment of the hotel domestic sewage; there was no cyanobacteria bloom explosion in the treated water. This study will aid in investigation the changes of microbial ecology in different types of water and providing the useful information for enhancing the cyanobacteria blooms control from ecological angle.

Pathogenesis of arteriovenous malformations in the absence of endoglin.

RATIONALE: Arteriovenous malformations (AVMs) result in anomalous direct blood flow between arteries and veins, bypassing the normal capillary bed. Depending on size and location, AVMs may lead to severe clinical effects including systemic cyanosis (pulmonary AVMs), hemorrhagic stroke (cerebral AVMs) and high output cardiac failure (hepatic AVMs). The factors leading to AVM formation are poorly understood, but patients with the familial disease hereditary hemorrhagic telangiectasia (HHT) develop AVMs at high frequency. As most HHT patients have mutations in ENG (endoglin) or ACVRL1 (activin receptor-like kinase 1), a better understanding of the role of these genes in vascular development is likely to reveal the etiology of AVM formation. OBJECTIVE: Using a mouse with a conditional mutation in the Eng gene, we investigated the sequence of abnormal cellular events occurring during development of an AVM. METHODS AND RESULTS: In the absence of endoglin, subcutaneous Matrigel implants in adult mice were populated by reduced numbers of new blood vessels compared with controls, and resulted in local venous enlargement (venomegaly). To investigate abnormal vascular responses in more detail, we turned to the more readily accessible vasculature of the neonatal retina. Endoglin-deficient retinas exhibited delayed remodeling of the capillary plexus, increased proliferation of endothelial cells and localized AVMs. Muscularization of the resulting arteriovenous shunts appeared to be a secondary response to increased blood flow. CONCLUSIONS: AVMs develop when an angiogenic stimulus is combined with endoglin depletion. Moreover, AVM formation appears to result from the combination of delayed vascular remodeling and an inappropriate endothelial cell proliferation response in the absence of endoglin.

[Effect of free surface flow wetland and subsurface flow wetland on bacterial diversity in Beijing Cuihu Wetland Park].

To achieve the effects of artificial wetland on the bacterial diversity, the culturable bacteria and total cell counts of three wetland cells, including sewage pond (SP), free surface wetland (SF) and subsurface flow wetland (SSF), were investigated using the traditional culture-dependent approach and flow cytometry method, based on the detecting the water quality. The bacterial diversity and dominant groups were also compared by PCR-DGGE profiles and 16S rDNA library technique based on its V3 region. Results show that SF and SSF cells can remove the nutrients effectively, the highest removal ratio of COD, total nitrogen, and total phosphorus reach to 42.33%, 52.92% and 41.4%, respectively; The total microbes are increased continuously with the treatment by SF and SSF, and the culturable bacteria clones are decreased after treatment by SF, and increased after further train by SSF. The Shannon-Weaver index is increased to 3.2850 from 3.0819 while the water flowing through SF, but decreased to 3.0181 after flowing through SSF; The dominant groups in SP include Actinobacteria, Cyanobacteria and alpha-Proteobacteria, reach to 38%, 18% and 18%, respectively; but the most dominant bacteria is changed to beta-Proteobacteria with the ratio of 32% and 44%, after treatment by SF and SSF, respectively. Cytophagal Flexibacter/Bacteroides (CFB) phylum is also increased to 24% finally. Therefore, while the Cuihu Wetland removing the nutrients,the bacterial counts, diversity and dominant groups are also changed,some beneficial bacteria in beta-Proteobacteria and CFB phylum increased, and part of those deleterious bacteria in Actinobacteria and Cyanobacteria decreased.

[Micro-ecology mechanism on microaerobic treatment performance at various influent COD concentrations or HRTs].

A lab-scale continuous experiment was designed to investigate the effect of influent COD concentrations (11,000, 15,000, 30,000 mg/L) or hydraulic retention time (HRT 42, 25 h) on the microareobic treatment performance of simulated high-strength organic wastewater. The molecular microbiological technologies, including Fluorescent in-situ hybridization-Flow Cytometry (FISH-FCM), Polymerase Chain Reaction-Denaturing Gradient Gel Electrophoresis (PCR-DGGE), and Biolog-FF assay method, were used to detect the variation of microbial community in the aerated column during the four pseudo-steady-state periods. The yeast contents remained > 99.9% throughout the overall experimental periods according to FISH-FCM. Increasing influent COD concentration brought on a rising MISS (2.0-7.3 g/L) and a reduced specific COD removal rate [2.3-1.7 kg/(kg x d)], structural (PCR-DGGE)/metabolic (Biolog FF) diversity index values of fungal community in the aerated column had an increase of (2.05-2.19)/(4.42-4.45). Shortening HRT brought on a reduced MISS (7.3-6.0 g/L) and a rising specific COD removal rate [1.7-2.8 kg/(kg x d)], structural (PCR-DGGE)/metabolic (Biolog FF) diversity index values of fungal community had a decrease of (2.19-0.79)/(4.45-4.36). Increasing influent COD concentration or shortening HRT has an absolutely adverse effect on the microaerobic treatment performance and micro-ecology in the aeration column although either of them can increase influent COD loading up to a higher level.