Synergistic mediating effect of edible fungal polysaccharides (Auricularia and Tremellan) and Crataegus flavonoids in hyperlipidemic rats.

Both edible fungal polysaccharides (Auricularia and Tremellan) and Crataegus flavonoids promote the balance of dyslipidemia, which have a positive biological regulating effect on intestinal flora. In this study, the extraction of water-soluble polysaccharides from Auricularia and Tremellan was investigated and optimized firstly. Polysaccharides and flavonoids were then combined to study the effects on the mediating role of abnormal blood lipid concentration and intestinal flora in vivo. The rats were divided into 10 groups, the NC (normal control), HM (model), PCI (Simvastatin control), PCII (Fenofibrate control), AAP (Auricularia auricular Polysaccharide), TFP (Tremella fuciformis Polysaccharide), HF (Crataegus Flavonoid), LDC (Low-dose combination), MDC (Medium dose combination), and HDC (High-dose combination), used to explore the impact of polysaccharides and flavonoids complex on state of blood lipid, liver, and intestinal flora of dyslipidemia rats. The results showed that the combination of polysaccharides and flavonoids could significantly decrease the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL-C), and increase the level of high-density lipoprotein cholesterol (HDL-C). It also significantly decreased the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and improved liver morphology. What is more, the HDC favorably alters the intestinal microflora balance, promotes intestinal integrity and mobility, and inhibits the growth of harmful bacteria such as Escherichia coli/Shigella and Clostridium compared with HM group. In brief, the combination of polysaccharides and flavonoids had a synergistic effect on the remission of dyslipidemia, and promoted health by improving lipid metabolism, protecting liver tissue, and regulating the intestinal flora in hyperlipidemia rats.

Assessment of Helicobacter pylori infection by deep learning based on endoscopic videos in real time.

BACKGROUND AND AIMS: Endoscopic assessment of Helicobacter pylori infection is a simple and effective method. Here, we aimed to develop a deep learning-based system named Intelligent Detection Endoscopic Assistant-Helicobacter pylori (IDEA-HP) to assess H. pylori infection by using endoscopic videos in real time. METHODS: Endoscopic data were retrospectively obtained from Zhejiang Cancer Hospital (ZJCH) for the development, validation, and testing of the system. Stored videos from ZJCH were used for assessing and comparing the performance of IDEA-HP with that of endoscopists. Prospective consecutive patients undergoing esophagogastroduodenoscopy were enrolled to assess the applicability of clinical practice. The urea breath test was used as the gold standard for diagnosing H. pylori infection. RESULTS: In 100 videos, IDEA-HP achieved a similar overall accuracy of assessing H. pylori infection to that of experts (84.0% vs. 83.6% [P = 0.729]). Nevertheless, the diagnostic accuracy (84.0% vs. 74.0% [P<0.001]) and sensitivity (82.0% vs. 67.2% [P<0.001]) of IDEA-HP were significantly higher than those of the beginners. In 191 prospective consecutive patients, IDEA-HP achieved accuracy, sensitivity, and specificity of 85.3% (95% CI: 79.0%-89.3%), 83.3% (95% CI: 72.8%-90.5%), and 85.8% (95% CI: 77.7%-91.4%), respectively. CONCLUSIONS: Our results show that IDEA-HP has great potential for assisting endoscopists in assessing H. pylori infection status during actual clinical work.

Correction: Synergistic effect of polysaccharides and flavonoids on lipid and gut microbiota in hyperlipidemic rats.

Correction for 'Synergistic effect of polysaccharides and flavonoids on lipid and gut microbiota in hyperlipidemic rats' by Yun-fei Bai et al., Food Funct., 2023, 14, 921-933, https://doi.org/10.1039/D2FO03031D.

Synergistic effect of polysaccharides and flavonoids on lipid and gut microbiota in hyperlipidemic rats.

Hyperlipidemia is a global health risk factor, and its development is closely related to the absorption and metabolism of lipids in the intestine. In this study, the Auricularia auricula polysaccharide, the Tremella polysaccharide, and hawthorn flavonoids were mixed by equal weight (HDC), and then its effect on the intervention in the intestine and blood lipids of hyperlipidemic rats on a high-fat diet (HFD) was investigated. The results revealed that HDC significantly inhibited the development of hyperlipidemia and reduced lipid levels and fat accumulation. In addition, HDC improved the edema deformation of intestinal epithelial cells, impaired the intestinal barrier induced by HFD, and improved the antioxidant capacity of the intestine. HDC showed a significant synergistic effect. Analysis of the gut microbiota by 16s rRNA gene sequencing showed that HDC reduced the ratio of Bacteroidetes/Firmicutes and the relative abundance of actinomycetes. At the genus level, the relative abundance of Lactobacillus, Rumincococcaceae-UCG-14, and Muribaculaceae was increased and the relative abundance of Allobaculum, Corynebacterium-1, Blautia, and Turicibucter was decreased. Intestinal lipidomics showed that HDC reduced the levels of DGDG, LPE, PG, phSM, PIP2, SoG1, and SM in the intestine of HFD rats, although there were no significant differences in LPE, PG, and phSM. 42 HDC-acting lipid biomarkers were screened. In conclusion, these findings support the potential of HDC intervention to prevent hyperlipidemia by regulating gut microbiota and lipid absorption and metabolism in the intestine.

Factors associated with non-lifting of colorectal mucosal lesions.

BACKGROUND: Endoscopic submucosal dissection (ESD) is an effective treatment for colorectal tumors. However, lesions that cannot be lifted after submucosal injection are not indication for ESD. This is because the procedure is difficult, and the lesions are often considered as tumor invasion or submucosal fibrosis. The aims of this study are to evaluate the efficacy and safety of ESD for non-lifting lesions and to analyze the causes of non-lifting phenomenon. METHODS: This retrospective study included 29 patients with non-lifting colon lesions resected by ESD from February 2018 to September 2021. Cases were observed for demographics, endoscopic findings, treatment outcomes, adverse events and endoscopic follow-up. We studied the pathological features of lesions to explore the reasons for non-lifting. RESULTS: Among 29 cases of non-lifting lesions, 20 lesions (69.0%) were 30 mm in diameter or larger. Most of lesions (96.6%) were non-lifting in center, and only one lesions (3.4%) had non-lifting of one side. The en bloc and curative resection rates of ESD were 100 and 86.2%, respectively. There was one (3.4%) delayed bleeding, no perforations and other complications. No tumor recurrence occurred during the follow-up period. For pathological features, 16 (55.2%) non-lifting lesions had submucosal fibrosis and only 4 cases (13.8%) had deep submucosal invasion. There were 9 cases (31.0%) of non-lifting lesions due to musculo-fibrous of muscularis propria anomaly (MMPA). CONCLUSION: MMPA is another reason for non-lifting signs besides invasive carcinomas and submucosal fibrosis. ESD should be considered in patients with large non-lifting adenoma instead of surgery.

Correlation of the detection rate of upper GI cancer with artificial intelligence score: results from a multicenter trial (with video).

BACKGROUND AND AIMS: The quality of EGD is a prerequisite for a high detection rate of upper GI lesions, especially early gastric cancer. Our previous study showed that an artificial intelligence system, named intelligent detection endoscopic assistant (IDEA), could help to monitor blind spots and provide an operation score during EGD. Here, we verified the effectiveness of IDEA to help evaluate the quality of EGD in a large-scale multicenter trial. METHODS: Patients undergoing EGD in 12 hospitals were consecutively enrolled. All hospitals were equipped with IDEA developed using deep convolutional neural networks and long short-term memory. Patients were examined by EGD, and the results were recorded by IDEA. The primary outcome was the detection rate of upper GI cancer. Secondary outcomes were part scores, total scores, and endoscopic procedure time, which were analyzed by IDEA. RESULTS: A total of 17,787 patients were recruited. The total detection rate of cancer-positive cases was 1.50%, ranging from .60% to 3.94% in each hospital. The total detection rate of early cancer-positive cases was .36%, ranging from .00% to 1.58% in each hospital. The average total score analyzed by IDEA ranged from 64.87 ± 16.87 to 83.50 ± 9.57 in each hospital. The cancer detection rate in each hospital was positively correlated with total score (r = .775, P = .003). Similarly, the early cancer detection rate was positively correlated with total score (r = .756, P = .004). CONCLUSIONS: This multicenter trial confirmed that the quality of the EGD result is positively correlated with the detection rate of cancer, which can be monitored by IDEA. (Clinical trial registration number: ChiCTR2000029001.).

Nuclear isoform of FGF13 regulates post-natal neurogenesis in the hippocampus through an epigenomic mechanism.

The hippocampus is one of two niches in the mammalian brain with persistent neurogenesis into adulthood. The neurogenic capacity of hippocampal neural stem cells (NSCs) declines with age, but the molecular mechanisms of this process remain unknown. In this study, we find that fibroblast growth factor 13 (FGF13) is essential for the post-natal neurogenesis in mouse hippocampus, and FGF13 deficiency impairs learning and memory. In particular, we find that FGF13A, the nuclear isoform of FGF13, is involved in the maintenance of NSCs and the suppression of neuronal differentiation during post-natal hippocampal development. Furthermore, we find that FGF13A interacts with ARID1B, a unit of Brahma-associated factor chromatin remodeling complex, and suppresses the expression of neuron differentiation-associated genes through chromatin modification. Our results suggest that FGF13A is an important regulator for maintaining the self-renewal and neurogenic capacity of NSCs in post-natal hippocampus, revealing an epigenomic regulatory function of FGFs in neurogenesis.

Changes in gut microbiota composition and diversity associated with post-cholecystectomy diarrhea.

BACKGROUND: Post-cholecystectomy diarrhea (PCD) frequently occurs in patients following gallbladder removal. PCD is part of the post-cholecystectomy (PC) syndrome, and is difficult to treat. After cholecystectomy, bile enters the duodenum directly, independent of the timing of meals. The interaction between the bile acids and the intestinal microbes is changed. Therefore, the occurrence of PCD may be related to the change in microbiota. However, little is known about the relationship between the gut microbiota and PCD. AIM: To better understand the role of the gut microbiota in PCD patients. METHODS: Fecal DNA was isolated. The diversity and profiles of the gut microbiota were analyzed by performing high-throughput 16S rRNA gene sequencing. The gut microbiota were characterized in a healthy control (HC) group and a PC group. Subsequently, the PC group was further divided into a PCD group and a post-cholecystectomy non-diarrhea group (PCND) according to the patients' clinical symptoms. The composition, diversity and richness of microbial communities were determined and compared. RESULTS: In the PC and HC groups, 720 operational taxonomic units (OTUs) were identified. The PC group had fewer OTUs than the HC group. ß-diversity was decreased in the PC group. This indicated decreased microbial diversity in the PC group. Fifteen taxa with differential abundance between the HC and PC groups were identified. In the PCD group compared to the PCND group, significant decreases in microbial diversity, Firmicutes/Bacteroidetes ratio, and richness of probiotic microbiota (Bifidobacterium and Lactococcus), and an increase in detrimental microbiota (Prevotella and Sutterella) were observed. Moreover, a negative correlation was found between Prevotella and Bifidobacterium. Using a Kyoto Encyclopedia of Genes and Genomes functional analysis, it was found that the abundances of gut microbiota involved in lipid metabolism pathways were markedly lower in the PCD group compared to the PCND group. CONCLUSION: This study demonstrated that gut dysbiosis may play a critical role in PCD, which provides new insights into therapeutic options for PCD patients.

Intelligent detection endoscopic assistant: An artificial intelligence-based system for monitoring blind spots during esophagogastroduodenoscopy in real-time.

BACKGROUND: Observation of the entire stomach during esophagogastroduodenoscopy (EGD) is important; however, there is a lack of effective evaluation tools. AIMS: To develop an artificial intelligence (AI)-assisted EGD system able to automatically monitor blind spots in real-time. METHODS: An AI-based system, called the Intelligent Detection Endoscopic Assistant (IDEA), was developed using a deep convolutional neural network (DCNN) and long short-term memory (LSTM). The performance of IDEA for recognition of gastric sites in images and videos was evaluated. Primary outcomes included diagnostic accuracy, sensitivity, and specificity. RESULTS: A total of 170,297 images and 5779 endoscopic videos were collected to develop the system. As the test group, 3100 EGD images were acquired to evaluate the performance of DCNN in recognition of gastric sites in images. The sensitivity, specificity, and accuracy of DCNN were determined as 97.18%,99.91%, and 99.83%, respectively. To assess the performance of IDEA in recognition of gastric sites in EGD videos, 129 videos were used as the test group. The sensitivity, specificity, and accuracy of IDEA were 96.29%,93.32%, and 95.30%, respectively. CONCLUSIONS: IDEA achieved high accuracy for recognition of gastric sites in real-time. The system can be applied as a powerful assistant tool for monitoring blind spots during EGD.

The Change of Soluble Programmed Cell Death-Ligand 1 in Glioma Patients Receiving Radiotherapy and Its Impact on Clinical Outcomes.

Background: The programmed cell death ligand 1 (PD-L1) plays a key role in glioma development. However, due to the specificity of glioma's anatomical position, the role of its expression as a tumor biomarker is limited. It has been proven that the levels of soluble programmed death-ligand 1 (sPD-L1) are associated with prognosis in many malignancies including glioma. However, the expression of sPD-L1 in glioma patients receiving radiotherapy (RT) remains unclear. The purpose of this study was to evaluate the concentration of sPD-L1 in the plasma of glioma patients before and after RT and to explore its relationship with clinical outcomes. Methods: Between October 2017 and September 2018, glioma patients treated with RT (30 ± 10 Gy, 2 Gy/f) were enrolled, and blood samples were collected before and after RT. We quantified the sPD-L1 levels by enzyme-linked immunosorbent assay (ELISA). The isocitrate dehydrogenase-1 (IDH-1) mutational status and Ki-67 expression of tumors were evaluated by immunohistochemistry. Glioma murine model were used to address whether circulating sPD-L1 molecules are directly targeted by an anti-PD-L1 antibody. The associations between sPD-L1 and clinical features were assessed with Pearson's or Spearman's correlation analysis. The progression-free survival (PFS) and overall survival (OS) were determined by the Kaplan-Meier method. Results: Sixty glioma patients were included, with a median age of 52 years. The proportions of grade I, II, III, and IV gliomas were 6.7%, 23.3%, 28.4%, and 41.6%, respectively. The baseline sPD-L1 levels were significantly associated with tumor grade, IDH-1 mutation status and Ki-67 expression. Using 14.35 pg/ml as the cutoff, significantly worse PFS and OS were both observed in patients with higher baseline levels of sPD-L1 (P = 0.027 and 0.008, respectively). RT significantly increased the mean level of sPD-L1 (P < 0.001). Further analysis showed that the level of sPD-L1 in IDH-1 mutation patients was higher than that in wild-type patients. Furthermore, an analysis of glioma murine model indicated that anti-PD-L1 antibody combine with RT can be a potentially powerful cancer therapy. Conclusion: This study reported that sPD-L1 might be a potential biomarker to predict the outcome in glioma patients receiving RT. The elevated level of sPD-L1 after RT suggested that the strategy of a combination of immune checkpoint inhibitors and RT might be promising for glioma patients, especially for those with IDH-1 mutations.

RBBP4 promotes colon cancer malignant progression via regulating Wnt/ß-catenin pathway.

BACKGROUND: Our previous study demonstrated that RBBP4 was upregulated in colon cancer and correlated with poor prognosis of colon cancer and hepatic metastasis. However, the potential biological function of RBBP4 in colon cancer is still unknown. AIM: To investigate the biological role and the potential mechanisms of RBBP4 in colon cancer progression. METHODS: Real-time polymerase chain reaction and western blot analysis were used to detect the expression of RBBP4 in colon cancer cell lines. The cell proliferation and viability of SW620 and HCT116 cells with RBBP4 knockdown was detected by Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine staining. The transwell assay was used to detect the invasion and migration capabilities of colon cancer cells with RBBP4 knockdown. Flow cytometry apoptosis assay was used to detect the apoptosis of colon cancer cells. Western blotting analysis was used to detect the expression of epithelial-mesenchymal transition and apoptosis related markers in colon cancer. The nuclear translocation of ß-catenin was examined by Western blotting analysis in colon cancer cells with RBBP4 knockdown. The TOPFlash luciferase assay was used to detect the effect of RBBP4 on Wnt/ß-catenin activation. The rescue experiments were performed in colon cancer cells treated with Wnt/ß-catenin activator LiCl and RBBP4 knockdown. RESULTS: We found that RBBP4 was highly expressed in colon cancer cell lines. The 5-ethynyl-2'-deoxyuridine assay showed that knockdown of RBBP4 significantly inhibited cell proliferation. RBBP4 inhibition reduced cell invasion and migration via regulating proteins related to epithelial-mesenchymal transition. Knockdown of RBBP4 significantly inhibited survivin-mediated apoptosis. Mechanistically, the TOPFlash assay showed that RBBP4 knockdown increased activity of the Wnt/ß-catenin pathway. Meanwhile, RBBP4 knockdown suppressed nuclear translocation of ß-catenin. With Wnt/ß-catenin activator, rescue experiments suggested that the role of RBBP4 in colon cancer progression was dependent on Wnt/ß-catenin pathway. CONCLUSION: RBBP4 promotes colon cancer development via increasing activity of the Wnt/ß-catenin pathway. RBBP4 may serve as a novel therapeutic target in colon cancer.

NG2 glia regulate brain innate immunity via TGF-ß2/TGFBR2 axis.

BACKGROUND: Brain innate immunity is vital for maintaining normal brain functions. Immune homeostatic imbalances play pivotal roles in the pathogenesis of neurological diseases including Parkinson's disease (PD). However, the molecular and cellular mechanisms underlying the regulation of brain innate immunity and their significance in PD pathogenesis are still largely unknown. METHODS: Cre-inducible diphtheria toxin receptor (iDTR) and diphtheria toxin-mediated cell ablation was performed to investigate the impact of neuron-glial antigen 2 (NG2) glia on the brain innate immunity. RNA sequencing analysis was carried out to identify differentially expressed genes in mouse brain with ablated NG2 glia and lipopolysaccharide (LPS) challenge. Neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice were used to evaluate neuroinflammatory response in the presence or absence of NG2 glia. The survival of dopaminergic neurons or glial cell activation was evaluated by immunohistochemistry. Co-cultures of NG2 glia and microglia were used to examine the influence of NG2 glia to microglial activation. RESULTS: We show that NG2 glia are required for the maintenance of immune homeostasis in the brain via transforming growth factor-ß2 (TGF-ß2)-TGF-ß type II receptor (TGFBR2)-CX3C chemokine receptor 1 (CX3CR1) signaling, which suppresses the activation of microglia. We demonstrate that mice with ablated NG2 glia display a profound downregulation of the expression of microglia-specific signature genes and remarkable inflammatory response in the brain following exposure to endotoxin lipopolysaccharides. Gain- or loss-of-function studies show that NG2 glia-derived TGF-ß2 and its receptor TGFBR2 in microglia are key regulators of the CX3CR1-modulated immune response. Furthermore, deficiency of NG2 glia contributes to neuroinflammation and nigral dopaminergic neuron loss in MPTP-induced mouse PD model. CONCLUSIONS: These findings suggest that NG2 glia play a critical role in modulation of neuroinflammation and provide a compelling rationale for the development of new therapeutics for neurological disorders.

Application of 4% formaldehyde under electronic colonoscope as a minimally invasive treatment of chronic hemorrhagic radiation proctitis.

BACKGROUND: To investigate the effectiveness of topical application of 4% formaldehyde as a minimally invasive treatment of rectal bleeding due to chronic radiation proctitis (CRP) under direct vision of electronic colonoscope. METHODS: The clinical data of 13 CRP patients complicated with ≥ grade II bleeding admitted to our hospital between January 2003 and December 2018 were retrospectively analyzed. Under the guidance of electronic colonoscope, 4% formaldehyde combined with 5-aminosalicylic acid (5-ASA) suppositories was topically applied. Patients were followed up for two months after treatment, and the therapeutic effectiveness was observed and analyzed. RESULTS: The rectal bleeding due to CRP was markedly reduced after topical application of 4% formaldehyde under colonoscope in all 13 patients. The bleeding stopped after one treatment session in 11 patients and after the second session in 2 patients. 5-ASA was also applied along with the use of 4% formaldehyde. The therapeutic effectiveness was satisfactory during the 1- and 2-month follow-up period. CONCLUSION: Topical application of 4% formaldehyde under the direct vision of colonoscope as a minimally invasive treatment for CRB-induced bleeding is a simple, effective, affordable, and repeatable technique without obvious complications, which deserves further exploration and promotion.

Retinoblastoma binding protein 4 up-regulation is correlated with hepatic metastasis and poor prognosis in colon cancer patients.

BACKGROUND: Retinoblastoma binding protein 4 (RBBP4) plays an essential role in the development of multiple cancers. However, its relationship with prognosis in colon cancer and colon cancer hepatic metastasis has not been elucidated. The aim of this study was to explore the relationship between RBBP4 expression and prognosis of colon cancer patients and to evaluate RBBP4 as a new prognostic marker in these patients. METHODS: Eighty colon cancer patients underwent surgical resection of the colon were enrolled. Among them, forty colon cancer patients suffered with hepatic metastasis. The colon cancer tissues, para-colon cancer tissues, and hepatic metastatic cancer tissues were collected from the pathological department for further analysis. The expression of RBBP4 proteins was examined by immunohistochemistry and correlated with clinicopathological parameters. The Cancer Genome Atlas (TCGA) database was used to validate the expression and explore its relationship with clinical characteristics. RESULTS: RBBP4 was up-regulated in the colon cancer tissues compared with the para-colon cancer tissues. The analysis of TCGA database verified the upregulation of RBBP4 in the colon cancer tissues and RBBP4 overexpression was correlated with nerve invasion and poor outcomes of chemotherapy. Moreover, the positive rate of RBBP4 expression in 40 colon cancer patients with hepatic metastasis was higher in the hepatic metastatic cancer tissues (39/40, 97.5%) than in the colon cancer tissues (26/40, 65.0%). Our clinicopathological analysis showed that RBBP4 expression was significantly correlated with vascular invasion, hepatic metastasis, and lymph node involvement (all P < 0.05). Additionally, the survival analysis demonstrated that RBBP4 over-expression was correlated with poor prognosis. CONCLUSIONS: RBBP4 was upregulated in the colon cancer. RBBP4 may be a novel predictor for poor prognosis of colon cancer and colon cancer hepatic metastasis.

Correlation between invasive microbiota in margin-surrounding mucosa and anastomotic healing in patients with colorectal cancer.

BACKGROUND: Impaired anastomotic healing is one of the major complications resulting from radical resection in colorectal cancer (CRC). Accumulating evidence suggests that intestinal microbiota is correlated with anastomotic healing. AIM: To explore the microbiota structural shift in margin-surrounding mucosa and evaluate the predictive ability of selected bacterial taxa for impaired anastomotic healing. METHODS: Margin-surrounding mucosa samples derived from 37 patients were collected to characterize the microbial community structure by 16s rRNA gene sequencing. The patients were divided into two groups according to the healing status of anastomoses: well-healing group (n = 30) and impaired-healing group (n = 7). Statistic differences in bacteria taxa were compared by Wilcoxon test and chi-squared test. The predictive ability of the selected bacterial taxa for the healing status of anastomoses was evaluated by the area under the receiver operator characteristic curve. RESULTS: Community structure shifts were observed in the impaired-healing group and well-healing group. Six bacterial species were found to be significantly correlated with anastomotic healing, and among these species, Alistipes shahii, Dialister pneumosintes, and Corynebacterium suicordis were considered as the predictive factors. Taking the known risk factor age into consideration, Alistipes shahii, Dialister pneumosintes, and Corynebacterium suicordis improved predictive ability for the healing status of anastomoses. CONCLUSION: These data show that Alistipes shahii, Dialister pneumosintes, and Corynebacterium suicordis could be considered as supplementary factors in the prediction of anastomosis healing status in patients after CRC radical resection.

Correlation between Contrast-Enhanced Ultrasound and Microvessel Density via CD31 and CD34 in a rabbit VX2 lung peripheral tumor model.

AIM: To evaluate the tumor angiogenesis in lung peripheral VX2 tumor model by contrast-enhanced ultrasound (CEUS) and to determine the correlation between CEUS parameters and microvessel density (MVD) calculated via CD31 and CD34 expression. MATERIAL AND METHODS: VX2 pulmonary tumors were created in eight Japanese white rabbits by implanting a VX2 sarcoma into the lower portion of the right lung through ultrasound guidance. Tumors were allowed to grow for 14-21 days to achieve a diameter of 7-15 mm, and were examined by CEUS using a SonoVue contrast agent. The results were recorded as digital video images, and the time-intensity curves and hemodynamic parameters were analyzed. Pathological tumor specimens were immediately obtained after the ultrasound examinations. Tumor specimens were stained with hematoxylin and eosin (H&E) and expressed as CD31 and CD34. The different endothelial cell markers were determined by immunohistochemical staining. MVD was calculated via CD 31 and CD34, and the relationship between CEUS parameters and MVD was analyzed. RESULTS: Two distinct types of microvessels were identified in lung peripheral VX2 tumors: differentiated (CD34+) and undifferentiated (CD31+) vessels. A significant correlation was found between CEUS parameters and undifferentiated MVD (CD31+ vessels) in lung peripheral VX2 tumors (p<0.05). A reverse correlation was observed between different MVDs. CONCLUSIONS: Two different degrees of differentiation of vascular endothelial cells (CD31 and CD34) exist in the rabbit lung peripheral VX2 tumor model. CD31 MVD can more effectively evaluate tumor angiogenesis compared with CD34 MVD. CEUS, as a non-invasive imaging method, can effectively evaluate tumor angiogenesis in rabbit peripheral lung cancer.

Lentinan dose dependence between immunoprophylaxis and promotion of the murine liver cancer.

Lentinan could exhibit significant biological activity favorable for human health and disease control such as the recovery of patients with liver cancer. In order to investigate the effect of lentinan dose dependence between immunoprophylaxis and promotion of cancer cell proliferation of the murine liver cancer, different concentrations of lentinan were prepared for the test in vitro (MTT assay) and in vivo (cumulative survival assay, spleen lymphocyte proliferation tests and peritoneal macrophage phagocytosis assays). New emerging proteins of the H22 cell incubated with lentinan was demonstrated by MS analysis and protein database searching. Lentinan was non-toxic for HL7702 cells but inhibited H22 cells proliferation obviously in a dose-dependent manner. In vivo, the proliferation of H22 hepatocarcinoma cells was inhibited by lentinan 0.4mg/kg body weight (L2, survival rate, 20%, PPP<0.01). Six proteins 60Sacidic ribosomal protein P2, Peroxiredoxin-2, Annexin A5, PDZ and LIM domain protein 1, Src substrate cortactin and Moesin were found as emerging proteins of the H22 cell incubated with high dose lentinan which related to cancer promotion closely. In conclusion, Thelentinan was relatively safe and could inhibit the proliferation of H22 cancer cells through immunity improvement when it's intake was in proper quantity.

Establishment of HPLC fingerprints of Qingfeiyucuo Pills and determination of four constituents / 中成药

AIM To establish the HPLC fingerprints of Qingfeiyucuo Pills (an agent for the management of acne,containing Scutellariae Radix,Eriobotryae Folium,Paeoniae Radix Rubra,etc.) and to determine the contents of four constituents.METHODS The analysis of methanol extract of Qingfeiyucuo Pills was carried out on a 35 ℃ thermostatic Agilent HC-C1s column (4.6 mm ×250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.4％ phosphoric acid flowing at 0.8 mL/min in a gradient elution manner,and the detection wavelength was set at 230 nm.RESULTS Eleven common peaks with the similarities of more than 0.9 were observed in the HPLC fingerprints of ten batches of samples.Paeoniflorin,hesperidin,baicalin and salvianolic acid B showed good linear relationships within the ranges of 0.08-0.25 μg,0.07-0.22 μg,0.2-0.60 μg and 0.06-0.18 μg,whose average recoveries were 98.7％,96.9％,97.4％ and 98.2％ with the RSDs of 0.98％,1.09％,0.82％ and 1.66％,respectively.CONCLUSION This sensitive and specific method can be used for the quality control of Qingfeiyucuo Pills.

Cell motility and spreading promoted by CEACAM6 through cyclin D1/CDK4 in human pancreatic carcinoma.

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) belongs to the human carcino-embryonic antigen (CEA) family. Numerous lines of studies have indicated that altered expression of CEACAM6 may have a role in carcinogenesis and development. However, few studies have defined functional roles and mechanisms of action. In the present study, the relationship between clinical and pathological parameters was also analyzed. The relative CEACAM6 protein expression of pancreatic carcinoma was significantly higher than that in non-cancerous tissue. Different clinical stages and lymph node metastasis between groups were significantly different (P<0.05). We used siRNA and forced-expression in multiple cell lines to define the role of CEACAM6 in the regulation of proliferation of pancreatic carcinoma in vitro and in vivo. Knockdown of endogenous CEACAM6 decreased proliferation of BxPC-3 and SW1990 cells. These changes significantly reduced cyclin D1 and CDK4 protein levels. Conversely, overexpression of CEACAM6 in MIA PaCa-2 cells stimulated proliferation and increased cyclin D1 and CDK4 protein levels. Our results confirm that CEACAM6 promoted cell proliferation, and these changes were mediated by cyclin D1/CDK4. These observations contribute to our understanding of the important roles of CEACAM6 in pancreatic carcinoma development and progression and could be a promising molecular target for the development of new diagnostic and therapeutic strategies of pancreatic carcinoma.