Contribution of the bacterial community of poorly fermented oat silage to biogas emissions on the Qinghai Tibetan Plateau.

To better utilize poorly fermented oat silage on the Qinghai Tibetan Plateau, 239 samples of this biomass were collected from the plateau temperate zone (PTZ), plateau subboreal zone (PSBZ), and nonplateau climatic zone (NPCZ) in the region and analyzed for microbial community, chemical composition and in vitro gas production. Climatic factors affect the bacterial α-diversity and ß-diversity of poorly fermented oat silage, which led to the NPCZ having the highest relative abundance of Lactiplantibacillus plantarum. Furthermore, the gas production analysis showed that the NPCZ had the highest maximum cumulative gas emissions of methane. Through structural equation modeling analysis, environmental factors (solar radiation) affected methane emissions via the regulation of lactate production by L. plantarum. The enrichment of L. plantarum contributes to lactic acid production and thereby enhances methane emission from poorly fermented oat silage. Notably, there are many lactic acid bacteria detrimental to methane production in the PTZ. This knowledge will be helpful in revealing the mechanisms of environmental factors and microbial relationships influencing the metabolic processes of methane production, thereby providing a reference for the clean utilization of other poorly fermented silage.

Potential for volatile fatty acid production via anaerobically-fermenting rice straw pretreated with silage effluent and phenyllactic acid.

To resolve environmental problems associated with rice straw and silage effluent disposal, silage effluent pretreating rice straw for the anaerobic production of volatile fatty acids (VFAs) was investigated. To prevent the lactic acid bacteria in silage effluent from inhibiting anaerobic fermentation, four phenyllactic acid (PLA) levels were set (0, 0.1, 0.3, 0.5 mg/kg). The total VFA yields of treatments pretreated only with silage effluent (CK) were higher than the groups combined with PLA during 15 days fermentation. Compared to PLA treatments, the total VFA of CK increased by 11.4 % ∼ 25.1 % on day 15. The CK showed higher lactic and propionic acid contents and lower pH values (<4.9). The PLA treatments decreased Lactobacillus abundance while increasing bacterial richness and evenness, and acetic and butyric acid contents. These demonstrated silage effluent has the potential to be used as a biological pretreatment for VFA production in anaerobic fermentation.

Epiphytic microbiota source stimulates the fermentation profile and bacterial community of alfalfa-corn mixed silage.

The epiphytic microbiota source on plants plays a crucial role in the production of high-quality silage. To gain a better understanding of its contribution, the microbiota of alfalfa (M1C0), corn (M0C1) and the resulting mixture (M1C1) was applied in alfalfa-corn mixed silage production system. M1C0 decreased ammonia-N levels in terms of total nitrogen (57.59-118.23 g/kg TN) and pH (3.59-4.40) values (p < 0.01), which increased lactic acid (33.73-61.89 g/kg DM) content (p < 0.01). Consequently, this resulted in higher residual water-soluble carbohydrate (29.13-41.76 g/kg DM) and crude protein (152.54-167.91 g/kg DM) contents, as well as lower NDF (427.27 g/kg DM) and ADF (269.53 g/kg DM) contents in the silage compared to M1C1- and M0C1-treated samples. Moreover, M1C0 silage showed significantly higher bacterial alpha diversity indices (p < 0.05), including the number of observed species and Chao1 and Shannon diversity indices, at the later stages of ensiling. Lactobacillus, Kosakonia and Enterobacter were the dominant bacterial species in silages, with a relative abundance of >80%. However, the abundance of Lactobacillus amylovorus in M0C1- and M1C1-treated silage increased (p < 0.01) in the late stages of ensiling. These findings confirmed that the epiphytic microbiota source exerts competitive effects during anaerobic storage of alfalfa-corn mixed silage.

Effect of lactic acid bacteria, yeast, and their mixture on the chemical composition, fermentation quality, and bacterial community of cellulase-treated Pennisetum sinese silage.

The present study investigated the effects of Lentilactobacillus buchneri, Saccharomyces cerevisiae, and a mixture of the two on the cellulose degradation and microbial community of cellulase-treated Pennisetum sinese (CTPS) during biological pretreatment. The CTPS was stored without additives (CK) or with L. buchneri (L), yeast (Y, S. cerevisiae), and their mixture (LY) under anaerobic conditions for 60 days. All inoculants enhanced the anaerobic fermentation of CTPS. In relative to L, inoculations with Y and LY decreased the cellulose level of fermented-CTPS by 8.90 ~ 17.13%. Inoculation with L inhibited the growth of Weissella cibaria during anaerobic storage. However, inoculations with LY increased the relative abundance of the homofermentative bacterium Lactiplantibacillus plantarum by 6.04%. Therefore, inoculating S. cerevisiae reduced the adverse effects of L. buchneri-stimulated fermentation on cellulose degradation by altering the bacterial community during anaerobic storage of P. sinese. This work provides a new insight for the subsequent anaerobic digestion of P. sinese.

Role of Lactiplantibacillus paraplantarum during anaerobic storage of ear-removed corn on biogas production.

To optimize the volatile fatty acid production for anaerobic fermentation, the ear-removed corn was ensiled without (control) or with Lactiplantibacillus plantarum (LP), Lacticaseibacillus paracasei (LC) and L. paraplantarum (LpP). Inoculation of LpP increased acetic acid content by 40%, and decreased butyric acid content by 38% in relative to control. Moreover, inoculation of LpP decreased the bacterial alpha diversity indices, while inherent species of Lentilactobacillus buchneri and L. hilgardii dominated the anaerobic fermentation. In particular, inoculation of LpP restricted the growth of yeasts and production of propionic acid at the early stage of storage, but continuously stimulated anaerobic fermentation, resulting in a higher maximal cumulative gas emissions of methane (by about 20 %) than that of LP and LC. Therefore, inoculation of LpP during anaerobic storage was favorable to produce intermediate metabolites (acetic acid) for subsequent biogas production of ear-removed corn.

Influence of Fermented-Moutai Distillers' Grain on Growth Performance, Meat Quality, and Blood Metabolites of Finishing Cattle.

The present study evaluated the effect of dietary supplementation with fermented-Moutai distillers' grain (FMDG) on the growth performance, meat quality, amino acid composition and blood metabolites of finishing cattle. Thirty cattle (2 years old; 237.55 ± 10.72 kg) were randomly assigned to one of three dietary supplementations: 0% FMDG (control), 15% FMDG (R1) and 30% FMDG (R2) [dry matter (DM) basis]. After 60 days, the inclusion of FMDG had no significant (p > 0.05) effects on the growth performance indices (dry matter intake, average daily gain and feed efficiency), meat quality (cooking yield, shear force, L*, a*, and b* values) or bovine blood biochemical indicators (except albumin and immunoglobulin A). Cattle fed R1 had the lowest (p = 0.001) loin eye area. Supplementation with FMDG significantly (p < 0.05) increased the beef contents of various amino acids (except isoleucine and arginine) compared with the control diet. Specifically, R2 significantly increased (p < 0.05) the total amino acid, essential amino acid, non-essential amino acid and umami amino acid contents in beef, while the difference in bitter amino acid content between different treatments was not significant (p = 0.165). These results suggest that it is feasible to include FMDG at up to 30% DM without affecting the growth performance, meat quality or blood metabolites of finishing cattle.

Effects of Additives on Silage Fermentation Characteristic and In Vitro Digestibility of Perennial Oat at Different Maturity Stages on the Qinghai Tibetan.

To effectively use local grass resources to cover the winter feed shortage on the Qinghai-Tibetan Plateau, the silage fermentation and in vitro digestibility of perennial oat (Helictotrichonvirescens Henr.) were investigated. Perennial oat was harvested at the heading/flowering stage, wilted under sunny conditions, chopped, vacuumed in small bag silos, and stored at ambient temperatures (5-15 °C) for 60 days. The silages were treated without (CK) or with local lactic acid bacteria (LAB) inoculant (IN1), commercial LAB inoculant (IN2), and sodium benzoate (BL). Control silages of perennial oat at early heading stage showed higher (p < 0.05) lactate and acetate contents and lower (p < 0.05) final pH, butyrate, and ammonia-N contents than those at the flowering stage. High levels of dry matter recovery (DMR) and crude protein (CP) were observed in IN1- and BL-treated silages, with high in vitro gas production and dry matter digestibility. Compared to CK, additives increased (p < 0.05) aerobic stability by inhibiting yeasts, aerobic bacteria, and coliform bacteria during ensiling. In particular, the local LAB inoculant increased (p < 0.05) concentrations of lactate, acetate and propionate, and decreased concentrations of butyrate and ammonia-N in silages. This study confirmed that local LAB inoculant could improve the silage quality of perennial oat, and this could be a potential winter feed for animals such as yaks on the Qinghai Tibetan Plateau.

Cost-effectiveness analysis of population-based screening of hepatocellular carcinoma: Comparing ultrasonography with two-stage screening.

AIM: To assess the cost-effectiveness of two population-based hepatocellular carcinoma (HCC) screening programs, two-stage biomarker-ultrasound method and mass screening using abdominal ultrasonography (AUS). METHODS: In this study, we applied a Markov decision model with a societal perspective and a lifetime horizon for the general population-based cohorts in an area with high HCC incidence, such as Taiwan. The accuracy of biomarkers and ultrasonography was estimated from published meta-analyses. The costs of surveillance, diagnosis, and treatment were based on a combination of published literature, Medicare payments, and medical expenditure at the National Taiwan University Hospital. The main outcome measure was cost per life-year gained with a 3% annual discount rate. RESULTS: The results show that the mass screening using AUS was associated with an incremental cost-effectiveness ratio of USD39825 per life-year gained, whereas two-stage screening was associated with an incremental cost-effectiveness ratio of USD49733 per life-year gained, as compared with no screening. Screening programs with an initial screening age of 50 years old and biennial screening interval were the most cost-effective. These findings were sensitive to the costs of screening tools and the specificity of biomarker screening. CONCLUSION: Mass screening using AUS is more cost effective than two-stage biomarker-ultrasound screening. The most optimal strategy is an initial screening age at 50 years old with a 2-year inter-screening interval.

Effectiveness of fecal immunochemical testing in reducing colorectal cancer mortality from the One Million Taiwanese Screening Program.

BACKGROUND: The effectiveness of fecal immunochemical testing (FIT) in reducing colorectal cancer (CRC) mortality has not yet been fully assessed in a large, population-based service screening program. METHODS: A prospective cohort study of the follow-up of approximately 5 million Taiwanese from 2004 to 2009 was conducted to compare CRC mortality for an exposed (screened) group and an unexposed (unscreened) group in a population-based CRC screening service targeting community residents of Taiwan who were 50 to 69 years old. Given clinical capacity, this nationwide screening program was first rolled out in 2004. In all, 1,160,895 eligible subjects who were 50 to 69 years old (ie, 21.4% of the 5,417,699 subjects of the underlying population) participated in the biennial nationwide screening program by 2009. RESULTS: The actual effectiveness in reducing CRC mortality attributed to the FIT screening was 62% (relative rate for the screened group vs the unscreened group, 0.38; 95% confidence interval, 0.35-0.42) with a maximum follow-up of 6 years. The 21.4% coverage of the population receiving FIT led to a significant 10% reduction in CRC mortality (relative rate, 0.90; 95% confidence interval, 0.84-0.95) after adjustments for a self-selection bias. CONCLUSIONS: This large, prospective Taiwanese cohort undergoing population-based FIT screening for CRC had the statistical power to demonstrate a significant CRC mortality reduction, although the follow-up time was short. Although such findings are informative for health decision makers, continued follow-up of this large cohort will be required to estimate the long-term impact of FIT screening if the covered population is expanded.

Fluoxetine a novel anti-hepatitis C virus agent via ROS-, JNK-, and PPARß/γ-dependent pathways.

More than 20% of chronic hepatitis C (CHC) patients receiving interferon-alpha (IFN-α)-based anti-hepatitis C virus (HCV) therapy experienced significant depression, which was relieved by treatment with fluoxetine. However, whether and how fluoxetine affected directly the anti-HCV therapy remained unclear. Here, we demonstrated that fluoxetine inhibited HCV infection and blocked the production of reactive oxygen species (ROS) and lipid accumulation in Huh7.5 cells. Fluoxetine facilitated the IFN-α-mediated antiviral actions via activations of signal transducer and activator of transcription (STAT)-1 and c-Jun amino-terminal kinases (JNK). Alternatively, fluoxetine elevated peroxisome proliferator-activated receptor (PPAR) response element activity under HCV infection. The inhibitory effects of fluoxetine on HCV infection and lipid accumulation, but not production of ROS, were partially reversed by the PPAR-ß, -γ, and JNK antagonists. Furthermore, fluoxetine intervention to the IFN-α-2b regimen facilitated to reduce HCV titer and alanine transaminase level for CHC patients. Therefore, fluoxetine intervention to the IFN-α-2b regimen improved the efficacy of anti-HCV treatment, which might be related to blockades of ROS generation and lipid accumulation and activation of host antiviral JNK/STAT-1 and PPARß/γ signals.

Rosiglitazone regulates anti-inflammation and growth inhibition via PTEN.

Peroxisome proliferator-activated receptor gamma (PPARγ) agonist has anti-inflammatory and anticancer properties. However, the mechanisms by which PPARγ agonist rosiglitazone interferes with inflammation and cancer via phosphatase and tensin homolog-(PTEN)-dependent pathway remain unclear. We found that lower doses (<25 µ M) of rosiglitazone significantly inhibited lipopolysaccharide-(LPS)-induced nitric oxide (NO) release (via inducible nitric oxide synthase, iNOS), prostaglandin E2 (PGE2) production (via cyclooxygenase-2, COX-2), and activation of Akt in RAW 264.7 murine macrophages. However, rosiglitazone did not inhibit the production of reactive oxygen species (ROS). In PTEN knockdown (shPTEN) cells exposed to LPS, rosiglitazone did not inhibit NO release, PGE2 production, and activation of Akt. These cells had elevated basal levels of iNOS, COX-2, and ROS. However, higher doses (25-100 µ M) of rosiglitazone, without LPS stimulation, did not block NO release and PGE2 productions, but they inhibited p38 MAPK phosphorylation and blocked ROS generation in shPTEN cells. In addition, rosiglitazone caused G1 arrest and reduced the number of cells in S + G2/M phase, leading to growth inhibition. These results indicate that the anti-inflammatory property of rosiglitazone is related to regulation of PTEN independent of inhibition on ROS production. However, rosiglitazone affected the dependence of PTEN-deficient cell growth on ROS.

A new insight into fecal hemoglobin concentration-dependent predictor for colorectal neoplasia.

We sought to assess how much of the variation in incidence of colorectal neoplasia is explained by baseline fecal hemoglobin concentration (FHbC) and also to assess the additional predictive value of conventional risk factors. We enrolled subjects aged 40 years and over who attended screening for colorectal cancer with the fecal immunochemical test (FIT) in Keelung community-based integrated screening program. The accelerated failure time model was used to train the clinical weights of covariates in the prediction model. Datasets from two external communities were used for external validation. The area under curve (AUC) for the model containing only FHbC was 83.0% (95% CI: 81.5-84.4%), which was considerably greater than the one containing only conventional risk factors (65.8%, 95% CI: 64.2-67.4%). Adding conventional risk factors did not make significant additional contribution (p = 0.62, AUC = 83.5%, 95% CI: 82.1-84.9%) to the predictive model with FHbC only. Males showed a stronger linear dose-response relationship than females, yielding gender-specific FHbC predictive models. External validation confirms these results. The high predictive ability supported by a dose-dependent relationship between baseline FHbC and the risk of developing colorectal neoplasia suggests that FHbC may be useful for identifying cases requiring closer postdiagnosis clinical surveillance as well as being an early indicator of colorectal neoplasia risk in the general population. Our findings may also make contribution to the development of the FHbC-guided screening policy but its pros and cons in connection with cost and effectiveness of screening should be evaluated before it can be applied to population-based screening for colorectal cancer.

Evaluation of abdominal ultrasonography mass screening for hepatocellular carcinoma in Taiwan.

UNLABELLED: Mass screening with abdominal ultrasonography (AUS) has been suggested as a tool to control adult hepatocellular carcinoma (HCC) in individuals, but its efficacy in reducing HCC mortality has never been demonstrated. This study aimed to assess the effectiveness of reducing HCC mortality by mass AUS screening for HCC based on a program designed and implemented in the Changhua Community-based Integrated Screening (CHCIS) program with an efficient invitation scheme guided by the risk score. We invited 11,114 (27.0%) of 41,219 eligible Taiwanese subjects between 45 and 69 years of age who resided in an HCC high-incidence area to attend a risk score-guided mass AUS screening between 2008 and 2010. The efficacy of reducing HCC mortality was estimated. Of the 8,962 AUS screening attendees (with an 80.6% attendance rate), a total of 16 confirmed HCC cases were identified through community-based ultrasonography screening. Among the 16 screen-detected HCC cases, only two died from HCC, indicating a favorable survival. The cumulative mortality due to HCC (per 100,000) was considerably lower in the invited AUS group (17.26) compared with the uninvited AUS group (42.87) and the historical control group (47.51), yielding age- and gender-adjusted relative mortality rates of 0.69 (95% confidence interval [CI]: 0.56-0.84) and 0.63 (95% CI: 0.52-0.77), respectively. CONCLUSION: The residents invited to community-based AUS screening for HCC, compared with those who were not invited, showed a reduction in HCC mortality by ∼ 31% among subjects aged 45-69 years who had not been included in the nationwide vaccination program against hepatitis B virus infection.

Application of quantitative estimates of fecal hemoglobin concentration for risk prediction of colorectal neoplasia.

AIM: To determine the role of the fecal immunochemical test (FIT), used to evaluate fecal hemoglobin concentration, in the prediction of histological grade and risk of colorectal tumors. METHODS: We enrolled 17881 individuals who attended the two-step colorectal cancer screening program in a single hospital between January 2010 and October 2011. Colonoscopy was recommended to the participants with an FIT of ≥ 12 ngHb/mL buffer. We classified colorectal lesions as cancer (C), advanced adenoma (AA), adenoma (A), and others (O) by their colonoscopic and histological findings. Multiple linear regression analysis adjusted for age and gender was used to determine the association between the FIT results and colorectal tumor grade. The risk of adenomatous neoplasia was estimated by calculating the positive predictive values for different FIT concentrations. RESULTS: The positive rate of the FIT was 10.9% (1948/17881). The attendance rate for colonoscopy was 63.1% (1229/1948). The number of false positive results was 23. Of these 1229 cases, the numbers of O, A, AA, and C were 759, 221, 201, and 48, respectively. Regression analysis revealed a positive association between histological grade and FIT concentration (ß = 0.088, P < 0.01). A significant log-linear relationship was found between the concentration and positive predictive value of the FIT for predicting colorectal tumors (R(2) > 0.95, P < 0.001). CONCLUSION: Higher FIT concentrations are associated with more advanced histological grades. Risk prediction for colorectal neoplasia based on individual FIT concentrations is significant and may help to improve the performance of screening programs.

Predictors of long-term survival in hepatocellular carcinomas: A longitudinal follow-up of 108 patients with small tumors.

AIM: Locoregional treatment [including percutaneous ethanol injection (PEI) therapy and transcatheter arterial chemoembolization (TACE)] provides an alternative treatment for early-diagnosed hepatocellular carcinoma (HCC). However, the long-term survival of patients after locoregional treatments remains unclear. PATIENTS AND METHODS: A total of 108 patients with small HCC not indicated for surgical hepatic resection were recruited between 1991 and 1999. All patients received first treatment with PEI therapy alone or combined with TACE. We followed-up these patients until the end of 2007. Clinical attributes and biological markers in association with long-term survival were collected. Significant predictors were identified by using proportional hazards regression model. RESULTS: The overall 1-, 3-, 5-, and 10-year cumulative survival of patients with HCC (<5 cm) were 88.8%, 59.4%, 29.4%, and 12.3%, respectively. Child-Pugh status, type of tumor (solitary or multiple), levels of pre-treatment aspartate aminotransferase (AST), and treatment modality were significantly associated with long-term survival after adjustment for age and gender. Child-Pugh B (hazard ration, HR=1.98, 95% confidence interval, CI=1.08-3.60) and higher level of pre-treatment AST (HR=1.91, 95% CI=1.18-3.08) were the two most significant predictors for risk of death from HCC-after adjusting for treatment modality and type of tumor. CONCLUSION: Child-Pugh score and AST level were demonstrated as the two major predictors for long-term survival in patients with small HCC not indicated for surgical treatment who underwent PEI-alone or combined with TACE. Clinical weights from Child-Pugh score and AST level are very informative for risk stratification and clinical surveillance of patients with small HCC treated by PEI-alone or combined with TACE.

Impact of faecal haemoglobin concentration on colorectal cancer mortality and all-cause death.

OBJECTIVE: To assess the effect of an incremental increase in faecal haemoglobin (f-Hb) concentration on colorectal cancer (CRC) mortality and all-cause death. DESIGN: We conducted an observational study of cohorts over time based on two population-based CRC screening programmes. SETTING: Two cities of Taiwan. PARTICIPANTS: 1233 individuals with CRC (217 prevalent cases and 1016 incident cases) and 2640 with colorectal adenoma (1246 prevalent cases and 1394 incident cases) found in the two cohorts of 59 767 and 125 976 apparently healthy individuals, aged 40 years and above, who had been invited to participate in screening since 2001 and 2003, respectively. MAIN OUTCOME MEASURES: Death from CRC and all-cause death ascertained by following up from the entire two cohorts over time until 2009. RESULTS: The effect of an incremental increase in f-Hb on the risk for CRC mortality was noted, increasing from a slightly increased risk for the category of f-Hb of 20-49 ng Hb/mL (adjusted HR (aHR)=1.09; 95% CI 0.68 to 1.75) to 11.67 (95% CI 7.71 to 17.66) for the group with f-Hb≥450 ng Hb/mL as compared with the group considered baseline with f-Hb of 1-19 ng Hb/mL (p<0.001). A similar but less marked increasing trend was found for all-cause mortality, aHR increasing from 1.15 (95% CI 1.07 to 1.24) for the group with f-Hb of 20-49 ng Hb/mL to 1.67 (95% CI 1.54 to 2.07) for the group with f-Hb≥450 ng Hb/mL. CONCLUSIONS: We substantiated the impacts of an incremental increase in f-Hb on the risk for death from CRC and all-cause death, consistently showing a significant gradient relationship. Both discoveries suggest that f-Hb may not only make contribution to facilitating individually tailored screening for CRC but also can be used as a significant predictor for life expectancy.

Accuracy of faecal occult blood test and Helicobacter pylori stool antigen test for detection of upper gastrointestinal lesions.

OBJECTIVE: Highly sensitive guaiac-based faecal occult blood (Hemoccult SENSA) and Helicobacter pylori stool antigen testing might help detect upper gastrointestinal lesions when appended to a colorectal cancer screening programme with faecal immunochemical testing. We evaluated the diagnostic accuracies of two stool tests in detecting upper gastrointestinal lesions. DESIGN: Cross-sectional design. SETTING: Hospital-based and community-based screening settings. PARTICIPANTS: A hospital-based deviation cohort of 3172 participants to evaluate test performance and a community-based validation cohort of 3621 to verify the findings. INTERVENTIONS: Three types of stool tests with bidirectional endoscopy as the reference standard. OUTCOMES: Sensitivity, specificity and positive and negative likelihood ratios. RESULTS: For detecting upper gastrointestinal lesions in cases with negative immunochemical tests, the sensitivity, specificity, and positive and negative likelihood ratios of the guaiac-based and H pylori antigen tests were 16.3% (95% CI 13.3% to 19.8%), 90.1% (88.9% to 91.2%), 1.64 (1.31 to 2.07), and 0.93 (0.89 to 0.97), respectively, and 52.5% (48.1% to 56.9%), 80.6% (79.0% to 82.1%), 2.71 (2.41 to 3.04) and 0.59 (0.54 to 0.65), respectively. For detecting upper gastrointestinal lesions in cases with normal colonoscopy, the results of the guaiac-based and H pylori antigen tests were 17.9% (14.8% to 21.5%), 90.1% (88.9% to 91.2%), 1.81 (1.45 to 2.26) and 0.91 (0.87 to 0.95), respectively, and 53.1% (48.6% to 57.4%), 80.7% (79.1% to 82.2%), 2.75 (2.45 to 3.08) and 0.58 (0.53 to 0.64), respectively. Within the community, positive predictive values of the immunochemical and H pylori antigen tests were 36.0% (26.0% to 46.0%) and 31.9% (28.3% to 35.5%), respectively, for detecting lower and upper gastrointestinal lesions, which were similar to expected values. CONCLUSIONS: The H pylori stool antigen test is more accurate than the guaiac-based test in the screening of upper gastrointestinal lesions in a population with high prevalence of H pylori infection and upper gastrointestinal lesions. It is applicable to add the H pylori antigen test to the immunochemical test for pan detection. TRIAL REGISTRATION: NCT01341197 (ClinicalTrial.gov).

Blockade of reactive oxygen species and Akt activation is critical for anti-inflammation and growth inhibition of metformin in phosphatase and tensin homolog-deficient RAW264.7 cells.

CONTEXT: Metformin is widely used for treatment of type 2 diabetes and has a potential application on the treatment of inflammation and cancer. Phosphatase and tensin homolog (PTEN) plays a critical role in cancer cell growth and inflammation; however, precise mechanisms remain unclear. OBJECTIVE: We aimed to investigate the possible mechanisms of how PTEN regulates metformin against cell growth and inflammation. MATERIALS AND METHODS: We established PTEN knockdown in RAW264.7 murine macrophages (shPTEN cells) to detect inflammatory mediators using commercial kits, production of reactive oxygen species (ROS) by flow cytometry, cell growth by MTT assay and phosphorylated levels of signal molecules by western blot. RESULTS: The shPTEN cells had a significant large amount of inflammatory mediators, such as inducible nitric oxide synthase (iNOS)/nitric oxide (NO) and cyclooxygenase-2 (COX-2)/prostaglandin E(2) (PGE(2)); and also elevated the production of ROS and increased cell proliferation. These effects were accompanied with the activation of Akt and p38 mitogen-activated protein kinase (MAPK), and the inactivation of an AMP-activated protein kinase (AMPK) activator and extracellular signal-regulated kinase 1/2. Pretreatment with metformin not only blocked these inflammatory mediators, but also caused growth inhibition induced by significant apoptosis. Furthermore, inactivation of Akt, blockade of ROS generation and independence of activations of AMPK and MAPK by metformin were also observed. CONCLUSION: Macrophages with PTEN deficiency developed a continuous inflammatory microenvironment, which further aggravated tumor cell growth. Moreover, metformin affected PTEN-deficient cells dependent of inhibition of ROS production and Akt activation against enlarged inflammatory mediators and/or cell growth in shPTEN cells.

Comparing the outcomes of two strategies for colorectal tumor detection: policy-promoted screening program versus health promotion service.

BACKGROUND: The Taiwanese government has proposed a population-based colorectal tumor detection program for the average-risk population. This study's objectives were to understand the outcomes of these screening policies and to evaluate the effectiveness of the program. METHODS: We compared two databases compiled in one medical center. The "policy-promoted cancer screening" (PPS) database was built on the basis of the policy of the Taiwan Bureau of National Health Insurance for cancer screening. The "health promotion service" (HPS) database was built to provide health check-ups for self-paid volunteers. Both the PPS and HPS databases employ the immunochemical fecal occult blood test (iFOBT) and colonoscopy for colorectal tumor screening using different strategies. A comparison of outcomes between the PPS and HPS included: (1) quality indicators-compliance rate, cecum reaching rate, and tumor detection rate; and (2) validity indicators-sensitivity, specificity, positive, and negative predictive values for detecting colorectal neoplasms. RESULTS: A total of 10,563 and 1481 individuals were enrolled in PPS and HPS, respectively. Among quality indicators, there was no statistically significant difference in the cecum reaching rate between PPS and HPS. The compliance rates were 56.1% for PPS and 91.8% for HPS (p < 0.001). The advanced adenoma detection rates of PPS and HPS were 1.0% and 3.6%, respectively (p < 0.01). The carcinoma detection rates were 0.3% and 0.4%, respectively (p = 0.59). For validity indicators, PPS provides only a positive predictive value for colorectal tumor detection. HPS provides additional validity indicators, including sensitivity, specificity, positive predictive value, and negative predictive value, for colorectal tumor screening. CONCLUSION: In comparison with the outcomes of the HPS database, the screening efficacy of the PPS database is even for detecting colorectal carcinoma but is limited in detecting advanced adenoma. HPS may provide comprehensive validity indicators and will be helpful in adjusting current policies for improving screening performance.

CD44/CD24 expression in recurrent gastric cancer: a retrospective analysis.

BACKGROUND: To correlate CD44/CD24 expression with gastric cancer recurrence and prognosis. Gastric cancer is the second leading cause of cancer mortality due to the high recurrence rate, of which the molecular signature has not yet been identified. METHODS: We retrospectively reviewed the hospital records of patients with gastric cancer. Among 500 patients receiving curative resection, 95 patients had recurrence. Twenty patients from the recurrence group (95 patients) and 20 patients from the non-recurrence group (405 patients) were randomly selected and identified as "study" and "control" groups, respectively. We reviewed patients' histological study of CD44/CD24 expression by performing immunohistochemistry and recurrence rate. RESULTS: Study group had higher TNM stage (III-IV) than control group (80% vs. 25%, P = 0.001). Proportion of lymph node metastasis was significantly higher in study group than that in control group (90% vs. 45%, P = 0.002), and proportion of patients with 5 or more metastatic lymph nodes was also significantly higher in study group than in control group (45% vs. 15%, P = 0.007). Univariate analysis revealed no difference in risk of gastric cancer recurrence between CD44+ and CD44- patients (OR = 1.00, 95% CI: 0.29-3.45, P =1.000). CD24+ patients showed no greater significance of gastric cancer recurrence than CD24- patients (OR = 1.86, 95% CI: 0.52-6.61, P = 0.339). After adjusting for other risk factors, the association of CD44 expression (aOR = 0.66, 95% CI: 0.10-4.26, P = 0.658), CD24 expression (aOR = 0.09, 95% CI: 0.01-1.35, P = 0.081) or combined (CD44/CD24) with gastric cancer recurrence were not significant. CONCLUSION: Neither individual expression of CD24 or CD44, nor combined expression of CD44/CD24 was associated with recurrence of gastric carcinoma.