The nonadherence and risk factors of eradication failure by sequential therapy as first-line anti-Helicobacter pylori treatment in real-world clinical practice.

BACKGROUND: The eradication rates of sequential therapy are high in clinical trials; however, the adherence for follow-up or the patient population in a real-world setting might be different from those in trails. This study investigates the effectiveness of sequential therapy in a real-world setting and the factors that lead to treatment failure. MATERIALS AND METHODS: In this retrospective study, patients receiving sequential therapy as a first-line anti-Helicobacter pylori (H. pylori) treatment in a real-world setting were reviewed. The age adjusted Charlson Comorbidity Index (age-CCI) and baseline variety of medications were reviewed to determine factors correlated with nonadherence for post-treatment testing and H. pylori eradication failure. RESULTS: A total of 1053 patients were reviewed. A total of 579 patients receiving sequential therapy were included in the analyses. Among them, 462 received post-treatment testing and were placed into the follow-up group. Thus, the post-treatment testing rate was 79.8%. Stroke was an independent factor of nonadherence for post-treatment testing. In the follow-up group, the eradication failure rate was 8.2%. Female sex (odds ratio [OR] 2.41 [95% CI 1.16-5.03], p = 0.02) and age-CCI ≥2 (OR 3.16 [1.05-9.48], p = 0.04) were independent factors of H. pylori eradication failure. The eradication failure rates were 14.4%, 7.8%, 7.1%, and 3.1% for the females with age-CCI ≥2, females with age-CCI <2, males with age-CCI ≥2, and males with age-CCI <2 subgroups, respectively (p = 0.027). CONCLUSIONS: In a real-world setting, the adherence rate of post-treatment testing for sequential therapy as a first-line anti-H. pylori treatment was found to be suboptimal. Female sex and age-CCI ≥2 were independent factors of eradication failure.

Precise application of topical tranexamic acid to enhance endoscopic hemostasis for peptic ulcer bleeding: a randomized controlled study (with video).

BACKGROUND AND AIMS: Peptic ulcer recurrent bleeding occurs in 20% to 30% of patients after standard endoscopic hemostasis, particularly within 4 days after the procedure. The application of additional tranexamic acid (TXA) to the ulcer may enhance hemostasis. This study investigated the effectiveness of TXA powder application on bleeding ulcers during endoscopic hemostasis. METHODS: This study enrolled patients who had peptic ulcer bleeding between March 2022 and February 2023. After undergoing standard endoscopic therapy, the patients were randomly assigned to either the TXA group or the standard group. In the TXA group, an additional 1.25 g of TXA powder was sprayed endoscopically on the ulcer. Both groups then received 3 days of high-dose (8 mg/h) continuous infusion proton pump inhibitor therapy. Second-look endoscopy was conducted on days 3 to 4. The primary end point of early treatment failure was defined as ulcer recurrent bleeding within 4 days or major stigmata of recent hemorrhage on the second-look endoscopy. RESULTS: Sixty patients (30 in each group) with peptic ulcer bleeding and balanced baseline characteristics were randomly assigned to a treatment group. The early treatment failure rate was lower in the TXA group (6.7%) than in the standard group (30%) (P = .042). The freedom from treatment failure periods for 4 and 28 days was significantly longer in the TXA group than in the standard group (P = .023). No adverse events from TXA were recorded. CONCLUSIONS: The precise delivery of topical TXA alongside standard endoscopic hemostasis reduced the early treatment failure rate in patients with bleeding peptic ulcers. (Clinical trial registration number: NCT05248321.).

Evolution of the Correa's cascade steps: A long-term endoscopic surveillance among non-ulcer dyspepsia and gastric ulcer after H. pylori eradication.

BACKGROUND: This study is aimed toward investigating the evolution of each Correa's step after Helicobacter pylori eradication in a long-term follow-up and exploring the factors correlated with a high-risk of gastric cancer. METHODS: A total of 1824 H. pylori-infected subjects were enrolled to receive screening endoscopy. Among them, 491 received surveillance endoscopy. The patients were divided into Correa's steps I to VI, from normal to gastric cancer. A group-based trajectory model was used to classify patients as persistent high-risk status or not. RESULTS: The prevalence rates of positive corpus-predominant gastritis index (CGI) were 20%-40% in all age groups and Correa's steps IV-V increased >35% after 50 years based on screening endoscopy. Successful eradication of H. pylori regressed CGI after the 1st year-and-thereafter (P < 0.05) and decreased Correa's step progression (Relative risk 0.66 [95% CI 0.49-0.89], P = 0.01); however, it did not regress OLGA and OLGIM. Not only in steps IV-V, but also in step III, the patients had a risk of developing gastric cancer (11.13-76.41 and 4.61 per 1000 person-years). Age (Hazard ratio 1.012 [1.003-1.020], P = 0.01), OLGA stages ≥ I (2.127 [1.558-2.903], P < 0.001), and OLGIM stages ≥ I (1.409 [1.119-1.774], P = 0.004) were correlated independently with a persistent high-risk status. CONCLUSION: The patients in Correa's steps III-V, but not I-II, were at risk of gastric cancer after H. pylori eradication. Age, OLGA stages ≥ I, and OLGIM stages ≥ I were independent factors correlated to a persistent high-risk of gastric cancer. The data may be useful when scheduling surveillance endoscopy for subjects in each Correa's step (NCT04527055).

Multi-Task Learning of Scanning Electron Microscopy and Synthetic Thermal Tomography Images for Detection of Defects in Additively Manufactured Metals.

One of the key challenges in laser powder bed fusion (LPBF) additive manufacturing of metals is the appearance of microscopic pores in 3D-printed metallic structures. Quality control in LPBF can be accomplished with non-destructive imaging of the actual 3D-printed structures. Thermal tomography (TT) is a promising non-contact, non-destructive imaging method, which allows for the visualization of subsurface defects in arbitrary-sized metallic structures. However, because imaging is based on heat diffusion, TT images suffer from blurring, which increases with depth. We have been investigating the enhancement of TT imaging capability using machine learning. In this work, we introduce a novel multi-task learning (MTL) approach, which simultaneously performs the classification of synthetic TT images, and segmentation of experimental scanning electron microscopy (SEM) images. Synthetic TT images are obtained from computer simulations of metallic structures with subsurface elliptical-shaped defects, while experimental SEM images are obtained from imaging of LPBF-printed stainless-steel coupons. MTL network is implemented as a shared U-net encoder between the classification and the segmentation tasks. Results of this study show that the MTL network performs better in both the classification of synthetic TT images and the segmentation of SEM images tasks, as compared to the conventional approach when the individual tasks are performed independently of each other.

An extended 36-week oral esomeprazole improved long-term recurrent peptic ulcer bleeding in patients at high risk of rebleeding.

BACKGROUND: Patients with Rockall scores ≥6 have an increased risk of long-term peptic ulcer rebleeding. This study was aimed toward investigating whether an extended course of oral esomeprazole up to 1 year decreased ulcer rebleeding in such patients. METHODS: We prospectively enrolled 120 patients with peptic ulcer bleeding and Rockall scores ≥6. After an initial 16-week oral proton pump inhibitor (PPI) treatment, patients were randomized to receive a 36-week course of oral twice-daily esomeprazole 20 mg (Group D, n = 60) or once-daily (Group S, n = 60). Thereafter, they were divided into the PPI-on-demand (n = 32) and PPI-discontinued (n = 77) subgroups. Our previous cohort with Rockall scores ≥6 served as the controls (Group C, n = 135); they received only an initial 8- to 16-week oral PPI. The primary and secondary outcomes were peptic ulcer rebleeding during the first year and the second year-and-thereafter, respectively. RESULTS: For the primary outcome, groups D and S comprised a higher proportion of rebleeding-free than Group C (P = 0.008 and 0.03, log-rank test). The competing-risks regression analysis confirmed that extended PPI use and American Society of Anesthesiologists classification were independent factors contributing to the primary outcome. For the secondary outcome, PPI-on-demand had a borderline higher proportion of rebleeding-free than Group C (P = 0.07, log-rank test); however, only the Rockall score was the independent factor. CONCLUSIONS: An extended 36-week course of oral esomeprazole 20 mg, twice- or once-daily for patients with Rockall scores ≥6 reduced ulcer rebleeding during the first year, but the effect needed to be further validated when PPIs were shifted to on-demand or discontinued thereafter (NCT02456012, 28/05/2015).

Age, male sex, smoking and metabolic syndrome as risk factors of advanced colorectal neoplasia for fecal immunochemical test negative patients.

BACKGROUND: Fecal immunochemical test (FIT) is worldwide strategy for colorectal cancer screening. The subjects with negative FIT still have the risk of an advanced colorectal neoplasia (AN), including adenoma with villous histology, high grade dysplasia or larger than 1 cm in size, or adenocarcinoma. The study determined the risk factors associated with AN in FIT-negative subjects. METHODS: The study included asymptomatic subjects who received health checkup colonoscopy and have provided FIT study within 6 months prior to colonoscopy. The risk factors to have AN in cases with negative FIT were analyzed. The numbers of colonoscopies needed to detect one AN were calculated for the subjects with different risk factors. RESULTS: There were 1411 cases, 85 with positive FIT and 1326 with negative FIT within 6 months before colonoscopy. In FIT positive and FIT negative cases, 45.9% and 34.6% were found to have colorectal adenoma, while 20.2% and 4.6% had AN, respectively. The univariate and multivariate logistic regression analyses showed that age more than 50 years old, male sex, smoking history and metabolic syndrome were the significant risk factors to have AN in the FIT negative cases. For cases with negative FIT to have these risk factors, the number of colonoscopies needed to detect one AN was 3.7, lower than 4.5 of the cases with positive FIT. CONCLUSION: For the cases with negative FIT, colonoscopy screening should be considered for those male patients over 50 years old, with a history of smoking and metabolic syndrome to detect AN.

The recurrent bleeding risk of a Forrest IIc lesion at the second-look endoscopy can be indicated by high Rockall scores ≥ 6.

BACKGROUND: The Forrest classification is widely applied to guide endoscopic hemostasis for peptic ulcer bleeding. Accordingly, practice guidelines suggest medical treatment only for ulcer with a Forrest IIc lesion because it has low rebleeding risk even without endoscopic therapy, ranging from 0 to 13%. However, the risk ranges widely and it is unclear who is at risk of rebleeding with such a lesion. This study assessed whether the Rockall score, which evaluates patients holistically, could indicate the risk of recurrent bleeding among patients with a Forrest IIc lesion at the second-look endoscopy. METHODS: Patients who had peptic ulcer bleeding with Ia-IIb lesions received endoscopic hemostasis at the primary endoscopy, and they were enrolled if their Ia-IIb lesions had been fading to IIc at the second-look endoscopy after 48- to 72-h intravenous proton pump inhibitor (PPI) infusion. Primary outcomes were rebleeding during the 4th-14th day and 4th-28th day after the first bleeding episode. RESULTS: The prospective cohort study enrolled 140 patients, who were divided into a Rockall scores ≥ 6 group or a Rockall scores < 6 group. The rebleeding rates in the Rockall scores ≥ 6 group and the Rockall scores < 6 group during the 4th-14th day and the 4th-28th day were 13/70 (18.6%) versus 2/70 (2.9%), p = 0.003 and 17/70 (24.3%) versus 3/70 (4.3%), p = 0.001, respectively, based on an intention-to-treat analysis and 5/62 (8.1%) versus 0/68 (0%), p = 0.023 and 6/59 (10.2%) versus 0/67 (0%), p = 0.009, respectively, based on a per-protocol analysis. The Kaplan-Meier curves showed that the Rockall scores ≥ 6 group had a significantly lower cumulative rebleeding-free proportion than the Rockall scores < 6 group (p = 0.01). CONCLUSIONS: Combined Rockall scores ≥ 6 on arrival with a Forrest IIc lesion at the second-look endoscopy can identify patients at risk of recurrent peptic ulcer bleeding following initial endoscopic and intravenous PPI treatment. Trial registration Trial registration identifier: NCT01591083.

Lead Time Bias May Contribute to the Shorter Life Expectancy in Post-colonoscopy Colorectal Cancer.

BACKGROUND: The long-term outcomes of post-colonoscopy colorectal cancer have varied in previous studies. Our nationwide cohort analysis estimated expected years of life lost to adjust for lead time bias. AIM: We recalculated the long-term outcomes for post-colonoscopy and detected colorectal cancer. METHODS: Patients with colorectal cancer registered in the Taiwan Cancer Registry between 2002 and 2009 were enrolled. The detected group included 22,169 cases of colorectal cancer confirmed within 6 months after a colonoscopy. The post-colonoscopy group included 1653 cancer patients who received a colonoscopy 6-60 months before diagnosis. Patients were followed up until 2011. We simulated age-, sex-, and calendar year-matched referents from life tables in the Taiwan National Vital Statistics using a Monte Carlo method. The life expectancy and expected years of life lost of the cancer patients were obtained from extrapolation of the logit transformation of the survival ratio between the cancer cohorts and the referent groups. RESULTS: Post-colonoscopy colorectal cancer had shorter life expectancies than detected cancer (stages 2-4: 13.6 vs. 16.1 years; 8.7 vs. 12.6 years; 2.1 vs. 4.1 years, p < 0.001). The loss-of-life expectancy did not show this trend after adjusting for lead time bias. Post-colonoscopy colorectal cancer was found at an older age, more often proximal, and was associated with previous endoscopic polypectomy procedures (p < 0.001). CONCLUSIONS: Post-colonoscopy colorectal cancer leads to a shorter life expectancy, which appears partially explained by the presence of lead time bias. Quality assurance for colonoscopy and close surveillance for high risk groups would reduce post-colonoscopy colorectal cancer.

Gonorrhea and chlamydia prevalence in different anatomical sites among men who have sex with men: a cross-sectional study in Guangzhou, China.

BACKGROUND: A high rectal and oropharyngeal sexually transmitted infection (STI) burden has been reported among men who have sex with men (MSM) in many regions, but little data exists on rectal and oropharyngeal STIs among MSM in China. The purpose of this study was to determine the prevalence of gonorrhea and chlamydia at different anatomic sites among MSM in Guangzhou, China. METHODS: We recruited a cross-sectional sample of MSM in one Chinese city and collected detailed information about socio-demographic characteristics and sexual behaviors. Men had urine, rectal, and pharyngeal swab samples tested for gonorrhea and chlamydia using nucleic acid amplification tests (NAAT). Univariate and multivariate logistic regressions were used to evaluate factors associated with gonorrhea and chlamydia. Among men without any STI symptoms, we also examined the prevalence of gonorrhea and chlamydia by anatomical site. RESULTS: We enrolled 463 men between January 2015 and March 2017. A total of 58/463 (12.5%) of men had gonorrhea and 84/463 (18.1%) had chlamydia. MSM with gonorrhea were more likely to have been recruited from the STI clinic (OR 3.41, 95% CI 1.94-5.99), living with HIV (OR 2.41, 95% CI 1.18-4.92), diagnosed had STI co-infection (OR 2.55, 95% CI 1.39-4.69). MSM with chlamydia were more likely to be students (OR 1.8, 95% CI 0.99-3.39). Most gonorrhea (34/58, 59%) and chlamydia (64/84, 76%) infections were not associated with STI symptoms. CONCLUSION: Asymptomatic gonorrhea and chlamydia infection were common in this sample of Chinese MSM. Further research is necessary to determine optimal STI screening programs.

Peptic ulcer bleeding patients with Rockall scores ≥6 are at risk of long-term ulcer rebleeding: A 3.5-year prospective longitudinal study.

BACKGROUND AND AIM: Patients with high Rockall scores have increased risk of rebleeding and mortality within 30 days after peptic ulcer bleeding, but long-term outcomes deserve follow-up after cessation of proton pump inhibitors. The paper aimed to validate whether patients with high Rockall scores have more recurrent ulcer bleeding in a 3.5-year longitudinal cohort. METHODS: Between August 2011 and July 2014, 368 patients with peptic ulcer bleeding were prospectively enrolled after endoscopic hemostasis to receive proton pump inhibitors for at least 8 to 16 weeks. These subjects were categorized into either a Rockall scores ≥6 group (n = 257) or a Rockall scores <6 group (n = 111) and followed up until July of 2015 to assess recurrent ulcer bleeding. RESULTS: The proportion of patients with rebleeding during the 3.5-year follow-up was higher in patients with Rockall scores ≥6 than in those with scores <6 (10.51 vs. 3.63 per 100 person-year, P = 0.004, log-rank test). Among patients with Rockall scores ≥6, activated partial thromboplastin time prolonged ≥1.5-fold (P = 0.045), American Society of Anesthesiologists physical status class ≥III (P = 0.02), and gastric ulcer (P = 0.04) were three additional independent factors found to increase rebleeding risk. The cumulative rebleeding rate was higher in patients with Rockall scores ≥6 with more than or equal to any two additional factors than in those with fewer than two additional factors (15.69 vs. 7.63 per 100 person-year, P = 0.012, log-rank test). CONCLUSIONS: Patients with Rockall scores ≥6 are at risk of long-term recurrent peptic ulcer bleeding. The risk can be independently increased by the presence of activated partial thromboplastin time prolonged ≥1.5-fold, American Society of Anesthesiologists class ≥III, and gastric ulcer in patients with Rockall scores ≥6.

The Role of Holter Monitoring in the Diagnosis of Early Repolarisation Pattern.

BACKGROUND: A slower heart rate can exaggerate J-point elevation in a 12-lead ECG. This study examined the role of Holter monitoring in the diagnosis of early repolarisation pattern (ERP). METHODS: We examined 24-hour Holter recordings of 4000 consecutive patients seen at an outpatient clinic, and found 500 patients (12.5%) with ERP (based on J-point elevation magnitude maximum value≥0.1mV on the Holter recording). The highest magnitude of J-point elevation, R wave amplitude, the ratio between J-point elevation magnitude and R-wave amplitude on the same ECG lead (J/R ratio), QRS interval, and QT/QTc interval were measured on the Holter recording and on a surface 12-lead ECG of the 500 patients with ERP. The magnitude of J-point elevation, J/R ratio, and QT/QTc interval were compared between three groups: nighttime Holter recording, daytime Holter recording, and daytime surface 12-lead ECG. RESULTS: The magnitude of J-point elevation of the nighttime Holter (0.20±0.10mV) was higher than that of the daytime in Holter (0.12±0.07mV, p<0.001) and the 12-lead ECG (0.12±0.06mV, p<0.001). There was no statistical difference in magnitude of J-point elevation between daytime Holter and surface 12-lead ECG. While all 500 patients were diagnosed with ERP based on J-point elevation maximum value J-point on Holter monitoring, only 425 (85%) patients could be diagnosed with ERP based on the surface 12-lead ECG. The J-point elevation maximum value on the nighttime Holter was negatively correlated with heart rate (r=-0.15, p=0.0007) and QTc (r=-0.13, p=0.0043), and positively correlated with R wave amplitude (r=0.46, p<0.0001), J/R ratio (r=0.69, p<0.0001), and QRS interval (r=0.29, p<0.0001). CONCLUSIONS: The J-point elevation on nighttime Holter recording was higher than that on daytime Holter and daytime surface 12-lead ECG, and there was misdiagnosis of ERP based on daytime surface 12-lead ECG. Holter monitoring has a complementary role in the diagnosis of ERP, especially in patients with a suspected diagnosis of ERP based on daytime surface 12-lead ECG.

Critical Care Resources in Guangdong Province of China: Three Surveys from 2005 to 2015.

OBJECTIVES: Data about the critical care resources in China remain scarce. The purpose of this study was to investigate the variation and distribution of critical care resources in Guangdong province from 2005 to 2015. DESIGN: Data in regard to critical care resources were collected through questionnaires and visits every 5 years from 2005. SETTING: All hospitals in Guangdong province were screened and hospitals that provide critical care services were enrolled. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: One hundred eleven, 158, and 284 hospitals that provide critical care services were enrolled in the three consecutive surveys respectively. The number of ICUs, ICU beds, intensivists, and nurses increased to 324, 3,956, 2,470, and 7,695, respectively, by 2015. Adjusted by population, the number of ICU beds per 100,000 (100,000) population increased by 147.7% from 2005 to 2015, and the number of intensivists and nurses per 100,000 population increased by 35.3% and 55.1% from 2011 to 2015. However, the numbers in the Pearl River Delta, a richer area, were higher than those in the non-Pearl River Delta area (ICU beds: 4.64 vs 2.58; intensivists: 2.90 vs 1.61; nurses: 9.30 vs 4.71 in 2015). In terms of staff training, only 17.85% of intensivists and 14.29% of nurses have completed a formal accredited critical care training program by 2015. CONCLUSIONS: Our study was the first one to investigate the trend and distribution of critical care resources in China. The quantity of ICU beds and staff has been increasing rapidly, but professional training for staff was inadequate. The distribution of critical care resources was unbalanced. Our study can be beneficial for healthcare policymaking and the allocation of critical care resources in Guangdong province and other provinces in China.

Male non-insulin users with type 2 diabetes mellitus are predisposed to gastric corpus-predominant inflammation after H. pylori infection.

BACKGROUND: Both H. pylori infection and diabetes increase the risk of gastric cancer. This study investigated whether patients with type 2 diabetes mellitus (T2DM) and H. pylori infection had more severe corpus gastric inflammation and higher prevalence of precancerous lesions than non-diabetic controls. METHODS: A total of 797 patients with type 2 diabetes mellitus were screened for H. pylori, of whom 264 had H. pylori infection. Of these patients, 129 received esophagogastroduodenoscopy to obtain topographic gastric specimens for gastric histology according to the modified Updated Sydney System, corpus-predominant gastritis index (CGI), Operative Link on Gastritis Assessment, and Operative Link on Gastric Intestinal Metaplasia Assessment. Non-diabetic dyspeptic patients who had H. pylori infection confirmed by esophagogastroduodenoscopy were enrolled as controls. RESULTS: The male as well as total T2DM patients had higher acute/chronic inflammatory and lymphoid follicle scores in the corpus than non-diabetic controls (p < 0.05). In contrast, the female T2DM patients had higher chronic inflammatory scores in the antrum than the controls (p < 0.05). In T2DM patients, the males had significantly higher rates of CGI than the females (p < 0.05). Multivariate logistic regression analysis showed that male patients (odds ratio: 2.28, 95% confidence interval: 1.11-4.69, p = 0.025) and non-insulin users (odds ratio: 0.33, 95% confidence interval: 0.15-0.74, p = 0.007) were independent factors for the presence of CGI in the H. pylori-infected patients with type 2 diabetes mellitus. CONCLUSIONS: Patients with type 2 diabetes mellitus and H. pylori infection had more severe corpus gastric inflammation than non-diabetic controls. Moreover, male gender and non-insulin users of T2DM patients were predisposed to have corpus-predominant gastritis after H. pylori infection. TRIAL REGISTRATION: ClinicalTrial: NCT02466919 , retrospectively registered may 17, 2015.

Determination of artemisitene in rat plasma by ultra-performance liquid chromatography/tandem mass spectrometry and its application in pharmacokinetics.

RATIONALE: Artemisitene shows a wide variety of pharmacological activities, such as antioxidant protection in vitro and in vivo. It has been identified as a novel Nrf2 inducer. However, there is no report on an ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) method to quantitate artemisitene in rat plasma and its application to a pharmacokinetic profile study. METHODS: An ACQUITY UPLC™ BEH Symmetry Shield RP18 column (1.7 µm, 2.1 mm × 100 mm) was used at a flow rate of 0.3 mL·min-1 . Mass detection was performed by electrospray ionization tandem mass spectrometry via multiple reaction monitoring (MRM) in positive mode. Plasma samples were pre-treated by a single-step extraction with 0.1% formic acid aqueous solutions-acetonitrile, and tolbutamide was used as internal standard. RESULTS: The calibration curve was from 0.98 to 1000 ng∙mL-1 (r2  = 0.995). The extraction recoveries were 61.5-79.4% and 81.7-94.6% for artemisitene and tolbutamide, respectively. The lower limit of quantification (LLOQ) was 0.98 ng∙mL-1 . The absolute bioavailability of artemisitene was 3.7% after intravenous and oral administration in rats. CONCLUSIONS: The UPLC/MS/MS assay was validated for linearity, accuracy, stability, extraction recovery, matrix effects, and intra-day and inter-day precision. The method, for the first time, achieved some pharmacokinetic parameters and was successfully applied to a pharmacokinetic study Copyright © 2017 John Wiley & Sons, Ltd.

Identification and positional distribution analysis of transcription factor binding sites for genes from the wheat fl-cDNA sequences.

The binding sites of transcription factors (TFs) in upstream DNA regions are called transcription factor binding sites (TFBSs). TFBSs are important elements for regulating gene expression. To date, there have been few studies on the profiles of TFBSs in plants. In total, 4,873 sequences with 5' upstream regions from 8530 wheat fl-cDNA sequences were used to predict TFBSs. We found 4572 TFBSs for the MADS TF family, which was twice as many as for bHLH (1951), B3 (1951), HB superfamily (1914), ERF (1820), and AP2/ERF (1725) TFs, and was approximately four times higher than the remaining TFBS types. The percentage of TFBSs and TF members showed a distinct distribution in different tissues. Overall, the distribution of TFBSs in the upstream regions of wheat fl-cDNA sequences had significant difference. Meanwhile, high frequencies of some types of TFBSs were found in specific regions in the upstream sequences. Both TFs and fl-cDNA with TFBSs predicted in the same tissues exhibited specific distribution preferences for regulating gene expression. The tissue-specific analysis of TFs and fl-cDNA with TFBSs provides useful information for functional research, and can be used to identify relationships between tissue-specific TFs and fl-cDNA with TFBSs. Moreover, the positional distribution of TFBSs indicates that some types of wheat TFBS have different positional distribution preferences in the upstream regions of genes.

A UPLC/MS/MS method for determination of protosappanin B in rat plasma and its application of a pharmacokinetic and bioavailability study.

Caesalpinia sappan L. is a traditional medicinal plant which is used for promoting blood circulation and cerebral apoplexy therapy in China. Previous reports showed that the extracts of Caesalpinia sappan L. could exert vasorelaxant activity and anti-inflammation activity. Protosappanin B is a major constituent of C. sappan L., and showed several important bioactivities. The separation was achieved by an Acquity UPLC BEH Symmetry Shield RP18 column (1.7 µm, 2.1 × 100 mm) column with the gradient mobile phase consisting of 5 mm ammonium acetate aqueous solution and acetonitrile. Detection was carried out by using negative-ion electrospray tandem mass spectrometry via multiple reaction monitoring. Plasma samples were preprocessed by an extraction with ethyl acetate, and apigenin was used as internal standard. The current UPLC-MS/MS assay was validated for linearity, accuracy, intraday and interday precisions, stability, matrix effects and extraction recovery. After oral and intravenous administration, the main pharmacokinetic parameters were as follows: peak concentrations, 83.5 ± 46.2 and 1329.6 ± 343.6 ng/mL; areas under the concentration-time curve, 161.9 ± 69.7 and 264.9 ± 56.3 µg h/L; and half-lives, 3.4 ± 0.9 and 0.3 ± 0.1 h, respectively. The absolute bioavailability in rats of protosappanin B was 12.2%. The method has been successfully applied to a pharmacokinetic and bioavailability study of protosappanin B in rats.

Genome-wide characterization of developmental stage- and tissue-specific transcription factors in wheat.

BACKGROUND: Wheat (Triticum aestivum) is one of the most important cereal crops, providing food for humans and feed for other animals. However, its productivity is challenged by various biotic and abiotic stresses such as fungal diseases, insects, drought, salinity, and cold. Transcription factors (TFs) regulate gene expression in different tissues and at various developmental stages in plants and animals, and they can be identified and classified into families according to their structural and specialized DNA-binding domains (DBDs). Transcription factors are important regulatory components of the genome, and are the main targets for engineering stress tolerance. RESULTS: In total, 2407 putative TFs were identified from wheat expressed sequence tags, and then classified into 63 families by using Hmm searches against hidden Markov model (HMM) profiles. In this study, 2407 TFs represented approximately 2.22% of all genes in the wheat genome, a smaller proportion than those reported for other cereals in PlantTFDB V3.0 (3.33%-5.86%) and PlnTFDB (4.30%-6.46%). We assembled information from the various databases for individual TFs, including annotations and details of their developmental stage- and tissue-specific expression patterns. Based on this information, we identified 1257 developmental stage-specific TFs and 1104 tissue-specific TFs, accounting for 52.22% and 45.87% of the 2407 wheat TFs, respectively. We identified 338, 269, 262, 175, 49, and 18 tissue-specific TFs in the flower, seed, root, leaf, stem, and crown, respectively. There were 100, 6, 342, 141, 390, and 278 TFs specifically expressed at the dormant seed, germinating seed, reproductive, ripening, seedling, and vegetative stages, respectively. We constructed a comprehensive database of wheat TFs, designated as WheatTFDB ( http://xms.sicau.edu.cn/wheatTFDB/ ). CONCLUSIONS: Approximately 2.22% (2407 genes) of all genes in the wheat genome were identified as TFs, and were clustered into 63 TF families. We identified 1257 developmental stage-specific TFs and 1104 tissue-specific TFs, based on information about their developmental- and tissue-specific expression patterns obtained from publicly available gene expression databases. The 2407 wheat TFs and their annotations are summarized in our database, WheatTFDB. These data will be useful identifying target TFs involved in the stress response at a particular stage of development.

Helicobacter pylori test-and-treat program can be cost-effective to prevent gastric cancer in Taiwanese adults: referred to the nationwide reimbursement database.

BACKGROUND: Helicobacter pylori infection increases the risk of gastric cancer. The study aimed to compare cost-effectiveness ratios of H. pylori test-and-treat programs to prevent gastric cancer in Taiwan, referring to the nationwide reimbursement database and expected years of life lost. MATERIALS AND METHODS: During 1998-2009, there were 12,857 females and 24,945 males with gastric adenocarcinoma in Taiwan National Cancer Registry. They were followed up to 2010 and linked to the reimbursement database of National Health Insurance and the national mortality registry to determine lifetime health expenditures and expected years of life lost. Cost-effectiveness ratios of H. pylori test-and-treat programs for prevention of gastric adenocarcinoma were compared between screenings with (13) C-urea breath test and with anti-H. pylori IgG. RESULTS: The test-and-treat program with anti-H. pylori IgG to prevent gastric adenocarcinoma had lower incremental cost-effectiveness ratios than that with (13) C-urea breath test in both sexes (females: 244 vs 1071 US dollars/life-year; males: 312 vs 1431 US dollars/life-year). Cost saving would be achieved in an endemic area where H. pylori prevalence was >73.5%, or by selecting subpopulations with high absolute risk reduction rates of cancer after eradication. Moreover, expected years of life lost of gastric adenocarcinoma were higher and the incremental cost-effectiveness ratios of test-and-treat programs were more cost-effective in young adults (30-69 y/o) than in elders (≥70 y/o). CONCLUSIONS: The test-and-treat program with anti-H. pylori IgG shall be cost-effective to prevent gastric adenocarcinoma in a high endemic area, especially beginning at 30 years of age when H. pylori prevalence rates become stabilized.