The fate of flavonoids after oral administration: a comprehensive overview of its bioavailability.

Despite advancements in synthetic chemistry, nature remains the primary source of drug discovery, and this never-ending task of finding novel and active drug molecules will continue. Flavonoids have been shown to possess highly significant therapeutic activities such as anti-inflammatory, anti-oxidant, anti-viral, anti-diabetic, anti-cancer, anti-aging, neuroprotective, and cardioprotective, etc., However, it has been found that orally administered flavonoids have a critical absorption disorder and, therefore, have low bioavailability and show fluctuating pharmacokinetic and pharmacodynamic responses. A detailed investigation is required to assess and analyze the variation in the bioavailability of flavonoids due to interactions with the intestinal barrier. This review will emphasize on the bioavailability and the pharmacological applications of flavonoids, key factors affecting their bioavailability, and strategies for enhancing bioavailability, which may lead to deeper understanding of the extent of flavonoids as a treatment and/or prevention for different diseases in clinics.

[Correlation between water state and texture during moistening of Paeoniae Radix Alba by LF-NMR/MRI].

The changes of active ingredients content, moisture status and texture characteristics during the moistening of Paeoniae Radix Alba were studied by low-field NMR and imaging(LF-NMR/MRI) and texture analyzer, so as to analyze the correlation between LF-NMR parameters, texture characteristics and active ingredient content of Paeoniae Radix Alba during the moistening at diffe-rent times. The results showed that MRI technology could directly, vividly and accurately characterize the degree of moistening and the process of water migration, and the degree of moistening was consistent with the judgment results of traditional experience. The characteristics of moisture migration and moisture phase state in the moistening process of Paeoniae Radix Alba were that the total water content increased and existed in the form of free water, with an increased moisture mobility. In the case of dampening, the total water content did not increase, but the more watery part of the medicinal material was distributed to the less watery part, with a reduced fluidity. Finally, the medicinal materials were moistened, which can be mutually verified with the MRI results. The free water content and the total water content of Paeoniae Radix Alba had extremely negative correlations with hardness, surface toughness, internal toughness, Paeoniflorin and albiflorin contents(P<0.01). It showed that the use of LF-NMR/MRI and texture analyzer could better characterize the moistening process. It provides data characterization for the scientific connotation of "less soaking and more moisturizing, and the drug is completely saturated with water", and the traditional experience of "observing the water head". The feasible and objective evaluation method was helpful to optimize the softening process parameters, scientifically standardize the operating specifications, define the scienti-fic connotation of traditional Chinese medicine softening, and promote the inheritance and innovation of traditional Chinese medicine processing.

The significance of OLGA and OLGIM staging systems in the risk assessment of gastric cancer: a systematic review and meta-analysis.

BACKGROUND: Despite extensive research on the criteria for the assessment of gastric cancer risk using the Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastritis/Intestinal-Metaplasia Assessment (OLGIM) systems, no comprehensive overview or systematic summary on their use is currently available. AIM: To perform a systematic review and meta-analysis to assess the efficacy of the OLGA and OLGIM staging systems in evaluating gastric cancer risk. METHODS: We searched various databases, including PubMed, EMBASE, Medline, and Cochrane's library, for articles published before March 2017 on the association between OLGA/OLGIM stages and risk of gastric cancer. Statistical analysis was performed using RevMan 5.30 and Stata 14.0, with the odds ratio, risk ratio, and 95% confidence interval as the effect measures. RESULTS: A meta-analysis of six case-control studies and two cohort studies, comprising 2700 subjects, was performed. The meta-analysis of prospective case-control studies demonstrated a significant association between the OLGA/OLGIM stages III/IV and gastric cancer. The Newcastle-Ottawa Scale (NOS) score reflected heterogeneity in the case-control studies on OLGA. Subgroup analysis of high-quality (NOS score ≥ 5) studies showed an association between OLGA stage III/IV and increased risk of gastric cancer; the association was also high in the remaining study with low NOS score. The association between higher stages of gastritis defined by OLGA and risk of gastric cancer was significant. CONCLUSIONS: This correlation implies that close and frequent monitoring of such high-risk patients is necessary to facilitate timely diagnosis of gastric cancer.

Chinese Sacbrood virus infection in Asian honey bees (Apis cerana cerana) and host immune responses to the virus infection.

Chinese Sacbrood virus (CSBV) is a positive-stranded RNAvirus that infects both the European honey bee (Apis mellifera) and the Asian honey bee (A. cerana). However, CSBV has much more devastating effects on Asian honey bees than on European honey bees, posing a serious threat to the agricultural and natural ecosystems that rely on A. cerana for pollination service. Using quantitative RT-PCR method, we conducted studies to examine the CSBV infection in Asian honey bee colonies and immune responses of individual bees in response to CSBV infection. Our study showed that CSBV could cause infection in different developmental stages of workers including eggs, larvae, pupae, newly emerged workers, and foraging workers. In addition, evaluating the tissue tropism and transmission of CSBV in infected bees showed that CSBV was detected in the ovaries, spermatheca, and feces of queens as well as semen of drones of the same colonies, suggesting an existence of vertical transmission of CSBV in Asian honey bees. Further, the detection of CSBV in colony food suggests that healthy bees could pick the infection by the virus-contaminated food, and therefore, a possible existence of a food-borne transmission pathway of CSBV in Asian bee colonies. The expression analysis of transcripts (defensin, abaecin, apidaecin, and hymenoptaecin) involving innate antiviral immune pathways showed that CSBV infection could induce significant immune responses in infected bees. However, the immune responses to CSBV infection varied among different development stages with eggs exhibiting the lowest level of immune expression and forager workers exhibiting the highest level of immune gene expression. The results obtained in the study yield important insights into the mechanisms underlying disease pathogenesis of CSBV infections in Asian honey bees and provide valuable information for a rational design of disease control measures.

Proposing an intelligent technique based on radial basis function neural network to forecast the energy spectrum of diagnostic X-ray imaging systems.

In digital subtraction angiography (digital subtraction total cerebral angiography), cardiac and macrovascular cardiography, anorectal radiology, fluoroscopy, and computed tomography (CT), a prior knowledge to X-ray energy spectrum is crucial for assessing the image quality and also calculating patient X-ray dosage. The present investigation's main objective is to propose an intelligent technique for faster calculating X-ray energy spectrum of medical imaging systems with different exposure settings of tube voltage, filter material, and thickness based on limited specific spectra. In this study, Monte Carlo N Particle (MCNP) simulation code was initially used to generate some limited X-ray spectra for tube voltages of 20, 30, 40, 50, 80, 100, 130, and 150 kV for two different filters of beryllium and aluminum with thicknesses of 0. 4, 0.8, 1.2, 1.6 and 2 mm. Tube voltage, type, and thickness of filter were used as the 3 inputs of 150 Radial Basis Function Neural Network (RBFNN) to forecast point by point of the X-ray spectrum. After training, the RBFNNs could forecast most of the X-ray spectra for tube voltages in the range of 20-150 kV and two various filters of aluminum and beryllium with thicknesses in the range of 0-2 mm.

Analysis of Risk Factors for Patient Safety Events Occurring in the Emergency Department.

OBJECTIVE: The aim of the study was to describe and analyze the risk factors associated with patient safety events (PSEs), defined as adverse events (AEs), preventable AEs (PAEs), and near-miss events (NMEs), in the emergency department (ED). METHODS: It was a retrospective cohort study using ED patients' data retrieved from January 2010 to December 2016. Quality assurance issues (QAIs) used as triggers included the following: issues during procedural sedation, death within 24 hours of admission, patients' and physicians' complaints, returns to the ED within 72 hours, and transfers to an intensive care unit within 24 hours. RESULTS: Of 383,586 ED visits, 6519 (1.7%) QAIs were reported with a PSEs incidence of 6.1%. Among the 397 PSEs, 258 were AEs including 82 PAEs, and 139 NMEs. During the 7-year period, we observed a fourfold increase in NMEs, and despite a decrease in the rate of AEs with the highest (3.1%) and lowest (0.8%) incidence in 2011 and 2016, respectively, the incidence of PAEs events remained relatively constant. Unadjusted analysis showed that ED waiting time, boarding time, ED length of stay (LOS), ED disposition, as well as diagnostic and QAIs were significantly related to PSEs (P < 0.05). Multivariable analysis showed that the type of QAIs and diagnostic were associated with PSEs (P < 0.001). Type of QAIs was a risk factor for AEs and PAEs occurrence and factors involved in NMEs were type of QAIs (P = 0.02) and ED LOS (P < 0.001). "The odds of a PSE occurring increased by 0.2% for each additional minute increase in the ED waiting time, by 5.2% for each additional boarding hour, and by 4.5% for each ED LOS hour." CONCLUSIONS: This study showed several potential risk factors for PSEs, especially ED LOS, type of QAIs, and diagnostic. Systematic interventions might have more impact on risk of PSE.

Establishment of loop-mediated isothermal amplification for Brucella detection using a warmer pad as a heating source.

The study sought to establish a sensitive and specific on-site loop-mediated isothermal amplification (LAMP) for Brucella heated using a warmer pad. LAMP primers specific to the conserved BvrR gene were designed, and the LAMP reaction was optimized. The heating characteristics of the warmer pad were investigated. The detection validity (specificity, sensitivity) of clinical samples by warmer-pad LAMP (WP-LAMP) was compared with that of qPCR. The WP-LAMP method displayed high specificity and sensitivity for five Brucella gene copies. The detection of 104 clinical samples was 97.1% concordant with quantitative polymerase chain reaction. The results showed the success of the WP-LAMP for on-site detection. The method requires no special equipment and is conducive to the prevention and control of brucellosis.

High-purity DNA extraction from animal tissue using picking in the TRIzol-based method.

TRIzol is used for the extraction of RNA, DNA and proteins from tissues or cells. Here, we present a simple picking method to extract DNA from tissues using TRIzol. Spectrophotometric analysis showed that the 260/280 and 260/230 nm optical density ratio of the picking method's DNA is ideal and better than that obtained by the classic TRIzol method. Gel electrophoresis showed that there was no RNA contamination, and the DNA had not degraded. DNA extracted by the picking method had the same performance in restriction enzyme digestion and quantitative PCR as that obtained by the traditional method. Viral DNA in the infected tissue was also obtained. This modified method facilitates various molecular biology assays.

Effects of malathion on the insect succession and the development of Chrysomya megacephala (Diptera: Calliphoridae) in the field and implications for estimating postmortem interval.

A field study on the effects of malathion on insect succession and the development of carrion flies on corpses, and its quantitative determination from the larvae on decomposing rabbit carrion was conducted. The rabbits were treated with malathion at concentrations of lethal, half-lethal and fourth-lethal doses. Malathion altered decomposition rates and species diversity: Chrysomya megacephala (Diptera: Calliphoridae) was the most abundant adult species in all the experiments; third instar larvae of Chrysomya rufifacies (Diptera: Calliphoridae) were not found on the toxic carcasses but were collected from the control; the appearance of beetles on the treated carcass was later by 1 to 3 days than on the control carcass. Development rate of the dominated species C. megacephala larvae and pupae was observed. Stepwise increases in the period of larval development, the maximum length of larvae, and weight of pupae were observed with increasing malathion concentrations. However, there was no significant difference in the duration of the pupal stage. The differences in development rate were sufficient to alter postmortem interval estimates based on larval development by 12 to 36 hours. The time of finding fresh pupae from the fourth-lethal carcass was 12 hours later than the control. Accumulations of the pesticide in larvae were observed, but no correlations were found between larvae concentrations and the initial quantity administered to rabbits.In conclusion, it is necessary to consider the effects of malathion present in decomposing bodies when estimating the postmortem interval based on entomological evidence. The results of this study have more practical implications for forensic investigations because it is under natural conditions.

A model prediction of long-term prognosis in patients with centrally located hepatocellular carcinoma undergoing hepatectomy.

BACKGROUND AND OBJECTIVES: The prognostic prediction for centrally located hepatocellular carcinoma (CL-HCC) after hepatectomy has not been well established. We aimed to develop prognostic nomograms for patients undergoing hepatectomy for CL-HCC. METHODS: A cohort of 380 patients who underwent curative hepatectomy for CL-HCC at our hospital between 2009 and 2015 were retrospectively studied. We randomly divided the subjects into training (n = 210) and validation (n = 170) groups. Univariate and multivariate survival analysis were used to identify prognostic factors. Visually orientated nomograms were constructed using Cox proportional hazards models. The performance of the nomogram was evaluated by the area under the ROC curve (AUC), calibration curve and compared with the conventional staging systems. RESULTS: The statistical nomogram for OS built on the basis of ALBI grade, tumor number, tumor size, classification, hepatectomy methods, capsule formation and microvascular invasion (MVI) had good calibration and discriminatory abilities, with AUC of 0.746 (65-month survival). The nomogram for DFS was based on tumor number, tumor size, classification, HBV-DNA load, capsule formation and MVI, with AUC of 0.733 (65-month survival). These nomograms showed satisfactory performance in the validation cohort (AUC, 0.733 for 65-month OS; and 0.702 for 65-month DFS). The AUC of our nomograms were greater than those of conventional staging systems in the validation cohort. CONCLUSION: The established nomograms might be useful for estimating survival for patients with CL-HCC after liver resection.

Sirt1 mediates improvement of isoflurane-induced memory impairment following hyperbaric oxygen preconditioning in middle-aged mice.

Hyperbaric oxygen (HBO) preconditioning (PC) has been suggested as a feasible method to provide neuroprotection from postoperative cognitive dysfunction (POCD). However, whether HBO-PC can ameliorate cognitive deficits induced by isoflurane, and the possible mechanism by which it may exert its effect, has not yet been clarified. In the present study, middle-aged mice were exposed to isoflurane anesthesia (1.5 minimal alveolar concentration [MAC]) for 2 h to establish a POCD model. After HBO preconditioning, cognitive function and expression of hippocampal sirtuin 1 (Sirt1), nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) were evaluated 24 h following isoflurane treatment, in the presence or absence of Sirt1 knockdown by short hairpin RNA (shRNA). HBO preconditioning increased the expression of Sirt1, Nrf2, and HO-1 and ameliorated memory dysfunction. Meanwhile, Sirt1 knockdown inhibited the expression of Nrf2 and HO-1 and attenuated the HBO preconditioning-associated memory improvement. Our results suggest that the application of HBO preconditioning is a useful treatment for POCD, and that Sirt1 may be a potential molecular target for POCD therapy.

Imbalanced cholesterol metabolism in Alzheimer's disease.

Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disease that is mainly caused by ß-amyloid accumulation. A large number of studies have shown that elevated cholesterol levels may perform a function in AD pathology, and several cholesterol-related gene polymorphisms are associated with this disease. Although numerous studies have shown the important function of cholesterol in AD pathogenesis and development, the underlying mechanism remains unclear. To further elucidate cholesterol metabolism disorder and AD, we first, review metabolism and regulation of the cholesterol in the brain. Second, we summarize the literature stating that hypercholesterolemia is one of the risk factors of AD. Third, we discuss the main mechanisms of abnormal cholesterol metabolism that increase the risk of AD. Finally, the relationships between AD and apolipoprotein E, PCSK9, and LRP1 are discussed in this article.

Amyloid-ß sequester proteins as blood-based biomarkers of cognitive decline.

INTRODUCTION: There are no blood-based biomarkers for cognitive decline in aging, or mild cognitive impairment (MCI) and Alzheimer's disease (AD). Cumulative evidence suggests that apolipoproteins, complement system, and transthyretin are involved in AD pathogenesis by sequestration of amyloid ß. However, there is no clinical study to assess the utility of "sequester proteins" in risk assessment and/or diagnosis of MCI and AD. METHODS: Serum levels of sequester proteins and their clinical potential in cognitive decline assessment were analyzed by longitudinal and cross-sectional studies using independent cohorts and were confirmed by a prospective study. RESULTS: A combination of apolipoprotein A1, complement C3, and transthyretin achieved an area under the curve of 0.89 (sensitivity 91% and specificity 80%) in MCI versus healthy controls and also discriminated individuals with mild cognitive decline from healthy controls. DISCUSSION: A set of sequester proteins could be blood-based biomarkers for assessment of early stages of cognitive decline.

Detection of telomerase activity in patients with mycosis fungoides.

OBJECTIVES: To detect telomerase activity in patients with mycosis fungoides (MF) and to study the role of telomerase in the tumorigenesis of MF. METHODS: The technique of PCR-ELISA was employed to detect telomerase activity in 35 patients with various stages of MF. RESULTS: 92.3% tumor stage of MF, 78.6% plaque stage of MF and 75.0% patch stage of MF had positive telomerase activity. The control samples had no telomerase activity. Telomerase activity in tumor stage of MF was significantly higher than that in plaque stage, while the latter was higher than that in patch stage. Telomerase activity was correlated with the stage of MF. CONCLUSION: High level of telomerase activity frequently occurred in patients with MF, suggesting that telomerase might play an important role in the tumorigenesis of MF and is a useful marker for the diagnosis of MF possibly.