Mazabraud's syndrome in female patients: Two case reports.

BACKGROUND: Mazabraud's syndrome (MS) is a rare and slowly progressive benign disease characterized by the concurrent presence of fibrous dysplasia of bone and intramuscular myxoma, and is thought to be associated with mutations of the GNAS gene. To date, only about 100 cases of MS have been reported in the literature, but its standard treatment strategy remains unclear. CASE SUMMARY: We report two cases of MS in young women who underwent different treatments based on their symptoms and disease manifestations. The first patient, aged 37, received internal fixation and intravenous bisphosphonate for a pathological fracture of the right femoral neck, excision of a right vastus medialis myxoma was subsequently performed for pain control, and asymptomatic psoas myxomas were monitored without surgery. Genetic testing confirmed a GNAS gene mutation in this patient. The second patient, aged 24, underwent right vastus intermedius muscle myxoma resection, and conservative treatment for fibrous dysplasia of the ilium. These patients were followed-up for 17 months and 3 years, respectively, and are now in a stable condition. CONCLUSION: Various treatments have been selected for MS patients who suffer different symptoms. The main treatment for myxomas is surgical resection, while fibrous dysplasia is selectively treated if the patient experiences pathological fracture or severe pain. However, given the documented instances of malignant transformation of fibrous dysplasia in individuals with MS, close follow-up is necessary.

Correlation between small-cell lung cancer serum protein/peptides determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and chemotherapy efficacy.

BACKGROUND: Currently, no effective measures are available to predict the curative efficacy of small-cell lung cancer (SCLC) chemotherapy. We expect to develop a method for effectively predicting the SCLC chemotherapy efficacy and prognosis in clinical practice in order to offer more pertinent therapeutic protocols for individual patients. METHODS: We adopted matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and ClinPro Tools system to detect serum samples from 154 SCLC patients with different curative efficacy of standard chemotherapy and analyze the different peptides/proteins of SCLC patients to discover predictive tumor markers related to chemotherapy efficacy. Ten peptide/protein peaks were significantly different in the two groups. RESULTS: A genetic algorithm model consisting of four peptides/proteins was developed from the training group to separate patients with different chemotherapy efficacies. Among them, three peptides/proteins (m/z 3323.35, 6649.03 and 6451.08) showed high expression in the disease progression group, whereas the peptide/protein at m/z 4283.18 was highly expressed in the disease response group. The classifier exhibited an accuracy of 91.4% (53/58) in the validation group. The survival analysis showed that the median progression-free survival (PFS) of 30 SCLC patients in disease response group was 9.0 months; in 28 cases in disease progression group, the median PFS was 3.0 months, a statistically significant difference (χ2 = 46.98, P < 0.001). The median overall survival (OS) of the two groups was 13.0 months and 7.0 months, a statistically significant difference (χ2 = 40.64, P < 0.001). CONCLUSIONS: These peptides/proteins may be used as potential biological markers for prediction of the curative efficacy and prognosis for SCLC patients treated with standard regimen chemotherapy.

Bi-level gene selection of cancer by combining clustering and sparse learning.

The diagnosis of cancer based on gene expression profile data has attracted extensive attention in the field of biomedical science. This type of data usually has the characteristics of high dimensionality and noise. In this paper, a hybrid gene selection method based on clustering and sparse learning is proposed to choose the key genes with high precision. We first propose a filter method, which combines the k-means clustering algorithm and signal-to-noise ratio ranking method, and then, a weighted gene co-expression network has been applied to the reduced data set to identify modules corresponding to biological pathways. Moreover, we choose the key genes by using group bridge and sparse group lasso as wrapper methods. Finally, we conduct some numerical experiments on six cancer datasets. The numerical results show that our proposed method has achieved good performance in gene selection and cancer classification.

Pan-Cancer Analysis and Validation of Opioid-Related Receptors Reveals the Immunotherapeutic Value of Toll-Like Receptor 4.

Introduction: The relationship between the expression of opioid-associated receptors and cancer outcomes is complex and varies among studies. Methods: This study focused on six opioid-related receptors (OPRM1, OPRD1, OPRK1, OPRL1, OGFR, and TLR4) and their impact on cancer patient survival. Bioinformatics analysis was conducted on 33 cancer types from The Cancer Genome Atlas database to examine their expression, clinical correlations, mechanisms in the tumor microenvironment, and potential for immunotherapy. Due to significantly lower expression of OPRM1, OPRD1, and OPRK1 compared to OGFR and TLR4, the analysis concentrated on the latter two genes. Results: OGFR was highly expressed in 16 tumor types, while TLR4 showed low expression in 13. Validation from external samples, the Gene Expression Omnibus, and the Human Protein Atlas supported these findings. The diagnostic value of these two genes was demonstrated using the Genotype-Tissue Expression database. Univariate Cox regression models and Kaplan-Meier curves confirmed OGFR's impact on prognosis in a cancer type-specific manner, while high TLR4 expression was associated with a favorable prognosis. Analysis of the tumor microenvironment using a deconvolution algorithm linked OGFR to CD8+ T cells and TLR4 to macrophages. Single-cell datasets further validated this correlation. In 25 immune checkpoint blockade treatment cohorts, TLR4 expression showed promise as an immunotherapy efficacy predictor in non-small cell lung cancer, urothelial carcinoma, and melanoma. Conclusion: In a pan-cancer analysis of 33 tissues, OGFR was consistently highly expressed, while TLR4 had low expression. Both genes have diagnostic and prognostic significance and are linked to immune cells in the tumor microenvironment. TLR4 has potential as an immunotherapeutic response marker.

[Effects of maize and peanut co-ridge intercropping on crop photosynthetic characteristics and intercropping advantages]. / çŽ‰ç±³å’ŒèŠ±ç”ŸåŒåž„é—´ä½œå¯¹ä½œç‰©å ‰åˆç‰¹æ€§å’Œé—´ä½œä¼˜åŠ¿çš„å½±å“.

To clarify the photosynthetic mechanism contributing to the enhancement of intercropping advantages through co-ridge intercropping of maize and peanut, we conducted a field randomized block experiment under two phosphorus levels of 0(P0) and 180 kg P2O5·hm-2(P180) with flat intercropping of maize and peanut (FIC) as the control. We analyzed the effects of co-ridge intercropping of maize and peanut (RIC) and groove-ridge intercropping of maize and peanut (GIC) on crop leaf area index (LAI), SPAD values, CO2 carboxylation ability, photosystems coordination (ΦPSⅠ/PSⅡ), and intercropping advantage of yield. The results showed that RIC significantly increased SPAD value at the silking stage of intercropping maize, and significantly improved the apparent quantum yield of photosynthesis (AQY), maximum electron transfer rate (Jmax), maximum rate of Rubisco carboxylation (Vc,max), net photosynthetic rate at the CO2 saturation (Amax) and ΦPSⅠ/PSⅡ of intercropping maize compared with those of FIC and GIC at silking stage and milking stage, but reduced the ratio of variable fluorescence Fk to amplitude Fj-Fo(Wk) and the ratio of variable fluorescence Fj to amplitude Fp-Fo(Vj) of the functional leaf photosystem Ⅱ (PSⅡ) at the milking stage of maize. There were no significant differences in these parameters between FIC and GIC. Compared with FIC, both RIC and GIC increased LAI of intercropping peanut at late growth stage and SPAD value at pod setting stage, significantly improved Vc,max, Amax, and ΦPSⅠ/PSⅡ, and reduced Wk and Vj values of intercropping peanut functional leaves at pod expanding stage. The difference in these parameters between RIC and GIC were not significant. The land equivalent ratio and intercropping advantages of RIC were higher than those of FIC and GIC. Phosphorus application could further promote Vc,max, Jmax, Amax and ΦPSⅠ/PSⅡ of intercropping maize and peanut, and significantly improve yield advantages of intercropping. The findings indicated that co-ridge intercropping could enhance CO2 carboxylation and fixation by improving photosynthetic electron transport and pho-tosystems coordination, improve the photosynthetic rate of functional leaves of maize and peanut, thus increase crop yield and intercropping advantages.

Aspirin increases chemosensitivity of colorectal cancer cells and inhibits the expression of toll-like receptor 4.

BACKGROUND: Chemotherapy resistance is an important bottleneck affecting the efficacy of chemotherapy in colon cancer. Therefore, improving the chemotherapy sensitivity of colorectal cancer cells is of great significance for improving the prognosis of patients with colon cancer. METHODS: CCK-8 assay was employed to examine the cell viability of colorectal cancer cell lines. Realtime-PCR and western blot were used to explore toll-like receptor 4 (TLR4) expression in colorectal cancer cell lines. The functions of TLR4 in the stemness of the colorectal cancer cell lines were analyzed by infecting cells with lentivirus containing TLR4 siRNA. RESULTS: We found that aspirin could effectively enhance the chemosensitivity of CT26 and HCT116 colorectal cancer cell lines. Aspirin can also inhibit the stemness of colorectal cancer cell including inhibiting the number of clone formation and reducing the volume and number of cell spheres and inducing the down-regulation of stemness-related genes. Besides that, aspirin also lead to down-regulation of TLR4 expression in colorectal cancer cells. The TLR4 positive colorectal cancer cells demonstrated a higher chemotherapy resistance potential than TLR4 negative colorectal cancer cells. In addition, the stemness of TLR4 positive colorectal cancer cells is stronger than TLR4 negative colorectal cancer cells. CONCLUSION: The results of our study indicate that aspirin increases chemosensitivity of colorectal cancer cells and inhibits the expression of toll-like receptor 4.

Anti-osteoporosis effects and regulatory mechanism of Lindera aggregata based on network pharmacology and experimental validation.

Osteoporosis (OP) is characterized by the flaccidity of bones or bone bi-disease caused by kidney deficiency. Lindera aggregate has been used to strengthen kidney function in China for thousands of years. It has been approved by Chinese Pharmacopoeia that the root of Lindera aggregata (RLA) can replenish and tonify the kidney, which is thought to be an effective way to alleviate OP. In this study, a network pharmacology approach was applied to explore the active components and potential mechanisms of RLA in osteoporosis treatment. Then, the ethanolic extract of the root of L. aggregata (EERL) was prepared and these predicted results were validated by prednisone-induced zebrafish embryos model. Moreover, the candidate compounds were identified by UPLC-ESI-MS/MS. The anti-OP results showed that EERL could significantly reverse the bone loss of zebrafish induced by prednisone. The mRNA expressions results showed that EERL decreased osteoclast bone resorption by regulating the RANK/RANKL/OPG system. Also, it increased bone formation by regulating the gene expressions of spp1, mmp2, mmp9, runx2b, alp, and entpd5a. Our results demonstrated the reliability of the network pharmacology method, and also revealed the anti-OP effect and potential mechanism of RLA.

Highly Efficient Electro-reforming of 5-Hydroxymethylfurfural on Vertically Oriented Nickel Nanosheet/Carbon Hybrid Catalysts: Structure-Function Relationships.

Ni-promoted electrocatalytic biomass reforming has shown promising prospect in enabling high value-added product synthesis. Here, we developed a novel hybrid catalyst with Ni nanosheet forests anchored on carbon paper. The hybrid catalyst exhibits high efficiency in electrooxidation of HMF to FDCA coupling with H2 production in high purity. The Ni nanosheets have small crystal grain sizes with abundant edges, which is able to deliver an efficient HMF oxidation to FDCA (selectivity >99 %) at low potential of 1.36 VRHE with high stability. The post-reaction structure analysis reveals the Ni nanosheets would transfer electrons to carbon and readily turn into NiOx and Ni(OH)x during the reaction. DFT results suggest high valence Ni species would facilitate the chemical adsorption (activation) of HMF revealing the reaction pathway. This work emphasizes the importance of the precise control of Ni activity via atomic structure engineering.

Manipulating interstitial carbon atoms in the nickel octahedral site for highly efficient hydrogenation of alkyne.

Light elements in the interstitial site of transition metals have strong influence on heterogeneous catalysis via either expression of surface structures or even direct participation into reaction. Interstitial atoms are generally metastable with a strong environmental dependence, setting up giant challenges in controlling of heterogeneous catalysis. Herein, we show that the desired carbon atoms can be manipulated within nickel (Ni) lattice for improving the selectivity in acetylene hydrogenation reaction. The radius of octahedral space of Ni is expanded from 0.517 to 0.524 Å via formation of Ni3Zn, affording the dissociated carbon atoms to readily dissolve and diffuse at mild temperatures. Such incorporated carbon atoms coordinate with the surrounding Ni atoms for generation of Ni3ZnC0.7 and thereof inhibit the formation of subsurface hydrogen structures. Thus, the selectivity and stability are dramatically improved, as it enables suppressing the pathway of ethylene hydrogenation and restraining the accumulation of carbonaceous species on surface.

Chyle Fat-Derived Stem Cells Conditioned Medium Inhibits Hypertrophic Scar Fibroblast Activity.

BACKGROUND: Hypertrophic scars (HSs) generally form after injury to the deep layers of the dermis and are characterized by excessive collagen deposition. An increasing amount of evidence has determined that human adipose tissue-derived mesenchymal stem cells attenuate fibrosis in various conditions. We explored the effect and possible mechanism of chyle fat-derived stem cells (CFSCs) on HS formation. METHODS: Hypertrophic scar-derived fibroblasts (HSFs) and CFSCs were isolated from individual patients. Third-passage CFSCs were isolated and cultured using a mechanical emulsification method, and their surface CD markers were analyzed by flow cytometry. The adipogenic and osteogenic differentiation capacity of the CFSCs was determined using oil red O staining and alizarin red S staining, respectively. Then, the effects of CFSCs on HSFs were assessed in vitro. Hypertrophic scar-derived fibroblasts were treated with starvation-induced conditioned medium from the CFSCs (CFSC-CM). The change in HSF cellular behaviors, such as cell proliferation, migration, and protein expression of scar-related molecules, was evaluated by cell counting assay, scratch wound assay, enzyme-linked immunosorbent assay, and western blotting. All data were analyzed using SPSS 17.0. RESULTS: The CFSCs expressed CD90, CD105, and CD73 but did not express CD34, CD45, or CD31. The CFSCs differentiated into adipocytes and osteoblasts under the appropriate induction conditions. Chyle fat-derived stem cells conditioned medium inhibited HSF proliferation and migration. The in vitro and ex vivo studies revealed that CFSC-CM decreased type I collagen, type III collagen, and α smooth muscle actin expression. CONCLUSIONS: Our results suggest that CFSCs are associated with the inhibition of fibrosis in HSFs by a paracrine effect. The use of CFSC-CM may be a novel therapeutic strategy for HSs.

The Effect of Chyle Fat Injection on Human Hypertrophic Scars in an Animal Model: A New Strategy for the Treatment of Hypertrophic Scars.

BACKGROUND: Chyle fat transplantation has shown positive effects on preexisting human hypertrophic scars (HSs) in a nude mouse HS graft model. METHODS: Hypertrophic scar fragments were obtained from 5 surgically treated burn patients and implanted into the backs of nude mice in 3 groups: group A, control; group B, triamcinolone; and group C, chyle fat. The specimens were implanted after the corresponding intralesional injection in each group, and the mice were observed for 4 weeks. In total, 18 mice and 72 scar specimens were studied. After 4 weeks, the HSs were removed from the mice. Then, the scar weights, histology, and decorin staining were assessed to evaluate the therapeutic efficacy. RESULTS: An obviously significant difference was observed in the HS weight reduction between groups A and C (P < 0.01), and a significant difference in the HS weight reduction was observed between groups A and B (P < 0.05). However, there was no significant difference between groups B and C. The treatment groups (groups B and C) showed strong decorin staining. Furthermore, the decorin staining was much stronger in group C than in group B (P < 0.05). Significant differences in extracellular matrix deposition were observed among the 3 groups, as determined by Masson trichrome staining. Both groups B and C showed significant therapeutic efficacy compared with group A, and group C exhibited a significant therapeutic effect compared with group B (P < 0.05). CONCLUSIONS: This study indicates that chyle fat grafting is beneficial for treating HSs.

Autologous chyle fat grafting for the treatment of hypertrophic scars and scar-related conditions.

BACKGROUND: Scarring is the product of natural restoration, yet its treatment remains challenging. Both collagen and fibroblasts are abnormally abundant in scars, leading to scar hyperplasia or contracture. Several clinical studies have reported that wrinkles at the recipient site are reduced, pores are narrowed, pigmentation is decreased, and skin is softened after autologous fat transplantation. In this study, we investigated the ability of autologous chyle fat injection to normalize the fibroblasts and collagen of scar tissue in 80 adult patients with hypertrophic scars resulting from severe burns received more than 1 year previously. METHODS: The patients underwent autologous chyle fat injection, and scar samples were collected at different time points. Differences in the number of adipocytes before and after chylosis were assessed by cell culture, and changes in the structural organization of the scars were detected via histologic and immunohistochemical analyses. RESULTS: After preparation, the chyle fat contained few autologous adipocytes and large amounts of extracellular matrix. Following the injection of chyle fat, the thickness, color, and elasticity of hypertrophic scar tissue tended toward normalization, and patient satisfaction increased. The three adipose tissue donor sites used for the preparation of chyle fat were the abdomen, buttocks, and inner thigh, of which the inner thigh yielded the best therapeutic outcomes. The density and quantity of fibroblasts in the scars decreased following the injection of chyle fat, and the arrangement, quantity, and shape of type III collagen fibers tended toward normalization. After three treatments, the results of immunohistochemical staining showed that type III collagen was significantly less abundant than before treatment. CONCLUSIONS: Autologous chyle fat transplantation has a good therapeutic effect on hypertrophic scar tissue. The injection of chyle fat into hypertrophic scar tissue reduced the density and quantity of fibroblasts and prompted the arrangement, quantity, and shape of type III collagen to normalize.

[Low-intensity pulsed ultrasound promotes extracellular matrix synthesis of human osteoarthritis chondrocytes].

Objective To investigate the effect of low-intensity pulsed ultrasound (LIPUS) on the extracellular matrix synthesis of human osteoarthritis (OA) chondrocytes and explore the underlying mechanism. Methods Human osteoarthritis chondrocytes were collected from abandoned articular cartilage. Then the cells were cultured and identified by toluidine blue staining and immunocytochemical staining of type 2 collagen. The passage 2 cells were randomly divided into 3 groups: control OA group, 30 mW/cm2 LIPUS-treated OA group, 30 mW/cm2 LIPUS combined with 5 µmol/L LY294002-treated OA group. LIPUS treatment was performed for 20 minutes per day, totally 7 days. The mRNA levels of Col2, aggrecan and matrix metalloprotease 13 (MMP-13) were determined by quantitative real-time PCR. The protein levels of Col2, aggrecan, Akt, p-Akt and MMP-13 were evaluated by Western blotting. Results Compared with the control OA group, the expressions of Col2 and aggrecan at both mRNA and protein levels significantly increased, and MMP-13 significantly reduced in the LIPUS-treated OA group. The p-Akt protein level was significantly elevated after LIPUS stimulation, but there was no significant difference in the Akt protein levels between the two groups. Moreover, LY294002, an inhibitor of PI3K/Akt, significantly suppressed the biological effect activated by LIPUS. Conclusion LIPUS enhances the synthesis and inhibits the degradation of the extracellular matrix in human osteoarthritis chondrocytes.

The EFFORT trial: Preoperative enoxaparin versus postoperative fondaparinux for thromboprophylaxis in bariatric surgical patients: a randomized double-blind pilot trial.

BACKGROUND: Prophylaxis for venous thromboembolism is routinely performed for all patients undergoing bariatric surgery. However, there is disagreement regarding the optimal dosing and duration of anticoagulant therapy. Furthermore, there is little data regarding the incidence of asymptomatic deep venous thrombosis (DVT) in this population. Our objective was to conduct a pilot randomized double blind study to evaluate the pharmacodynamic parameters of 2 different anticoagulation medications (enoxaparin and fondaparinux) administered to patients undergoing bariatric surgery. METHODS: From July 2010 to August 2013, 198 consecutive bariatric surgery patients from an academic institution were randomized in a double blinded manner to receive either 40 mg enoxaparin twice daily or 5mg fondaparinux sodium once daily. Antifactor Xa activity was measured on all patients in both study arms, 3 hours after the first dose (on the day of the operation), immediately before the second dose (postoperative day one), and 3 hours after the second dose. At the routine 2 week postoperative visit, patients underwent magnetic resonance venography (MRV) to detect DVT. The primary outcome was attainment of therapeutic antifactor Xa levels. The secondary outcome was DVT, as detected by MRV. Safety outcomes were perioperative bleeding, perioperative complications, and death. RESULTS: Of 198 patients randomized, 177 underwent MRV and 137 had interpretable antifactor Xa levels. Nearly half of the patients (47.4%) did not attain target prophylactic antifactor Xa levels. Adequate antifactor Xa levels were more common with fondaparinux (74.2%) than with enoxaparin (32.4%). Antifactor Xa levels were also associated with preoperative D-dimer level. 4 of the 175 patients who underwent MRV developed DVT, 2 in each arm of the study. No major adverse events occurred in either arm. CONCLUSION: Fondaparinux was much more likely to produce target prophylactic antifactor Xa levels than enoxaparin. Both regimens appear to be equally effective at reducing the risk of DVT. Further prospective studies are needed to determine the optimal DVT prophylaxis regimen in the bariatric surgical population.

[Correction of secondary lip whistle deformities and nasal base depression after bilateral cleft lip repair with lip subdermal soft tissue flap].

OBJECTIVE: To explore a new method to correct secondary lip whistle deformities and nasal base depression after bilateral complete cleft lip (BCCL) repair with lip subdermal soft tissue flap. METHODS: Bilateral subdermal soft tissue "C" flaps and "lambda" flap were designed to repair secondary deformities of nasal base and reconstruct vermilion tubercle in patients after BCCL repair. RESULTS: Good results were achieved in all the patients with primary healing. No flap necrosis happened. The result was satisfactory. CONCLUSIONS: With bilateral subdermal soft tissue "C" flaps and " lambda" flap, nasal base depression deformities and lip whistle deformities can be corrected. It is an ideal method for correction of deformities after BCCL repair.

[Preliminary study of in vitro chondrogenesis by co-culture of chondrocytes and adipose-derived stromal cells].

OBJECTIVE: To explore the feasibility of in vitro chondrogenesis by co-culture of chondrocytes and adipose-derived stromal cells (ADSCs) so as to confirm the hypothesis that chondrocytes can provide chondrogenic microenvironment to induce chondrogenic differentiation of ADSCs. METHODS: Human ADSCs and porcine auricular chondrocytes were in vitro expanded respectively and then were mixed at the ratio of 7:3 (ADSCs: chondrocytes). 200 microl mixed cells (5.0 x 10(7)/ml) were seeded onto a polyglycolic acid/polylactic acid (PGA/PLA) scaffold, 8 mm in diameter and 2 mm in thickness, as co-culture group. Chondrocytes and ADSCs with the same cell number were seeded respectively onto the scaffold as positive control group and negative control group. 200 microl chondrocytes (1.5 x 10(7)/ml) were seeded as low concentration chondrocyte group. There were 6 specimens in each group. All specimens were harvested after in vitro culture for 8 weeks in DMEM plus 10% FBS. Gross observation, histology, immunohistochemistry, wet weight measurement and glycosaminoglycan (GAG) quantification were used to evaluate the results. Multiple-sample t-test statistics analysis was done to compare the difference of wet weight and glycosaminoglycan(GAG) content between the groups. RESULTS: Cells in all groups had fine adhesion to the scaffold and could secrete extracellular matrix. In co-culture group and positive control group, cell-scaffold constructs could maintain the original size and shape during in vitro culture. At 8 weeks, cartilage-like tissue formed in gross appearance and histological features, and abundant type II collagen could be detected by immunohistochemistry. Wet weight and glycosaminoglycan(GAG) content of co-culture group were respectively (174 +/- 12) mg and (7.6 +/- 0.4) mg. There were respectively 75% (P < 0.01) and 79% (P<0.01) of those of positive control group. In negative control group, however, constructs shrunk gradually without mature cartilage lacuna in histology. In low concentration chondrocyte group, constructs also shrunk obviously with small amount of cartilage formation at the edge area of the construct, and wet weight was (85 +/- 5) mg, which was 37% (P<0.01) of that of positive control group. CONCLUSIONS: Chondrocytes can provide chondrogenic microenvironment to induce chondrogenic differentiation of ADSCs and thus promote the in vitro chondrogenesis of ADSCs.

Comparative study of conventional colonoscopy, magnifying chromoendoscopy, and magnifying narrow-band imaging systems in the differential diagnosis of small colonic polyps between trainee and experienced endoscopist.

BACKGROUND: Removal of colorectal neoplastic polyps can reduce the incidence of colorectal cancers. It is important to distinguish neoplastic from nonneoplastic polyps. We compared the ability of a trainee and an experienced endoscopist in distinguishing between neoplastic polyps and nonneoplastic polyps by conventional white-light, magnifying narrow-band imaging (NBI), and magnifying chromoendoscopy. MATERIALS AND METHODS: One hundred and sixty-three small colorectal polyps from 104 patients were studied. All polyps were diagnosed by trainees and experienced endoscopists using conventional white-light, magnifying NBI, and magnifying chromoendoscopy. The kappa values of interobserver agreement between trainees and experienced endoscopists were evaluated before this study. Sensitivity, specificity, and diagnostic accuracy were assessed by reference to histopathology. The first 50 polyps were diagnosed by the trainee as the first stage and the rest 113 polyps were diagnosed as the second stage. RESULTS: Magnifying NBI and magnifying chromoendoscopy were significant better than conventional white-light by the experienced endoscopist (diagnostic accuracy: NBI 85.3%, chromoendoscopy 87.7%, conventional view 74.8%). No significant differences were found for the trainee. The kappa values (0.77 approximately 0.85) were good for each endoscopic modality for the experienced endoscopist. However, only NBI and chromoendoscopy had acceptable kappa values (0.40 approximately 0.48) for the trainee. The trainee improved diagnostic accuracy in the second stage, but not yielded the level of the experienced endoscopist. CONCLUSION: Magnifying NBI and magnifying chromoendoscopy had a better interobserver agreement than conventional white-light among trainees and experienced endoscopists. The trainee needs learning time to improve diagnostic ability, even using a new modality such as magnifying NBI.

Dysfunction of Nrf-2 in CF epithelia leads to excess intracellular H2O2 and inflammatory cytokine production.

Cystic fibrosis is characterized by recurring pulmonary exacerbations that lead to the deterioration of lung function and eventual lung failure. Excessive inflammatory responses by airway epithelia have been linked to the overproduction of the inflammatory cytokine IL-6 and IL-8. The mechanism by which this occurs is not fully understood, but normal IL-1beta mediated activation of the production of these cytokines occurs via H2O2 dependent signaling. Therefore, we speculated that CFTR dysfunction causes alterations in the regulation of steady state H2O2. We found significantly elevated levels of H2O2 in three cultured epithelial cell models of CF, one primary and two immortalized. Increases in H2O2 heavily contributed to the excessive IL-6 and IL-8 production in CF epithelia. Proteomic analysis of three in vitro and two in vivo models revealed a decrease in antioxidant proteins that regulate H2O2 processing, by > or =2 fold in CF vs. matched normal controls. When cells are stimulated, differential expression in CF versus normal is enhanced; corresponding to an increase in H2O2 mediated production of IL-6 and IL-8. The cause of this redox imbalance is a decrease by approximately 70% in CF cells versus normal in the expression and activity of the transcription factor Nrf-2. Inhibition of CFTR function in normal cells produced this phenotype, while N-acetyl cysteine, selenium, an activator of Nrf-2, and the overexpression of Nrf-2 all normalized H2O2 processing and decreased IL-6 and IL-8 to normal levels, in CF cells. We conclude that a paradoxical decrease in Nrf-2 driven antioxidant responses in CF epithelia results in an increase in steady state H2O2, which in turn contributes to the overproduction of the pro-inflammatory cytokines IL-6 and IL-8. Treatment with antioxidants can ameliorate exaggerated cytokine production without affecting normal responses.

Premedication with pronase or N-acetylcysteine improves visibility during gastroendoscopy: an endoscopist-blinded, prospective, randomized study.

AIM: To assess the efficacy of premedicaton with pronase or N-acetylcysteine (NAC) at 20 min before upper gastrointestinal (UGI) endoscopy and to determine whether pronase or NAC pretreatment influences the reliability of the rapid urease test. METHODS: A total of 146 patients were prospectively and randomly assigned into the study groups according to different premedications before endoscopy. One endoscopist assessed mucosal visibility (MV) with scores ranged from 1 to 4 at four sites in the stomach. The sum of the MV scores from these four locations was defined as the total mucosal visibility (TMV) score. Identification of H pylori was performed using CLO test, histology, and serology. RESULTS: The Group with pronase premedication had a significantly lower TMV score than did the groups with gascon and gascon water (P < 0.001 and P < 0.01, respectively). The group with NAC had a significantly lower TMV score than the group with gascon (P < 0.01) and a trend of a lower MV score than the group with gascon water (P = 0.06). The TMV score did not significantly differ between the group with pronase and the group with NAC (P = 0.39 and P = 0.14, respectively). The sensitivity and specificity of the CLO test were 92.5% and 93.9%, respectively, in groups premedicated with pronase and NAC together. CONCLUSION: Premedication with pronase or NAC at 20 min before UGI endoscopy improves the mucosal visibility of the stomach. Neither pronase nor NAC produces any obvious interference with the CLO test for the identification of H pylori infection.

The cytotoxicity and mechanisms of 1,2-naphthoquinone thiosemicarbazone and its metal derivatives against MCF-7 human breast cancer cells.

We have investigated the antitumor functions and mechanisms of 1,2-naphthoquinone-2-thiosemicarbazone (NQTS) and its metal complexes (Cu(2+), Pd(2+), and Ni(2+)) against MCF-7 human breast cancer cells. The cells were dosed with these complexes at varying concentrations, and cell viability was measured by a sulforhodamine B (SRB) method. To study mechanisms of action, the complexes were incubated with topoisomerase II (topo II) and supercoiled DNA, linear DNA, nicked open DNA, and relaxed DNA were detected by agarose gel electrophoresis. The results revealed that these complexes are effective antitumor chemicals in inhibiting MCF-7 cell growth, with Ni-NQTS being the most effective among the complexes studied. Our data also indicated that Ni-NQTS is more effective than the commercial antitumor drug, etoposide, based on IC(50) values. The mechanistic study of action showed that metal complexes of NQTS, NQ, and NQTS can only stabilize the single-strand nicked DNA, but not double-strand breakage intermediates. In addition, metal derivatives of these ligands, but not the parent NQ and NQTS, exerted an antagonizing effect on topoisomerase II activity. In summary, chemicals with or without metal derivatives might possess different chemical-topoisomerase II-DNA interactions.