10-Day versus 14-day bismuth quadruple therapy for first-line eradication of Helicobacter pylori infection: a randomised, open-label, non-inferiority trial.

Background: Bismuth quadruple therapy is currently consensus recommendation for first-line Helicobacter pylori (H. pylori) treatment; however, the optimal duration is unknown. We compared the efficacy of 10-day bismuth quadruple therapy with that of 14-day bismuth quadruple therapy for first-line eradication. Methods: For our multicentre, parallel randomised, open-label, and non-inferiority study, we recruited H. pylori treatment-naïve patients from one medical centre and one teaching hospital in Taiwan. Patients were randomly assigned (1:1) to receive 10-day (PBMT-10) or 14-day (PBMT-14) bismuth quadruple therapy. The primary outcome was the eradication rate as determined by intention-to-treat (ITT) and per-protocol (PP) analyses. The eradication rates between the two groups were compared using a one-sided α value of 0.025 and a non-inferiority margin of 7%. The secondary outcomes were the rate of adverse effects. The trial is registered with ClincialTrials.gov (NCT04527055). Findings: From August 3, 2020 to April 28, 2023, 313 H. pylori treatment-naïve patients (PBMT-10 = 157; PBMT-14 = 156) were enrolled. 35 patients were excluded from PP analyses. The eradication rates (95% CI) for PBMT-10 and PBMT-14 were respectively 92.4% (88.2%-96.5%) and 92.9% (88.9%-97.0%) by ITT analyses, and 97.9% (95.5%-100.0%) and 99.3% (97.8%-100.0%) by PP analyses. The eradication rates for PBMT-10 were non-inferior to those for PBMT-14 (absolute difference [lower boundary of the one-sided 97.5% CI] -0.6% [-6.7%], PNI = 0.020 in ITT analyses, -1.4% [-5.8%], PNI = 0.007 in PP analyses). The rates of overall adverse effects (54.1% versus 57.1%, P = 0.604) were similar between the two groups; nevertheless, the rates of dizziness (18.5% versus 34.0%, P = 0.003) and vomiting (4.5% versus 12.8%, P = 0.008) were lower in PBMT-10 than in PBMT-14. Interpretation: The 10-day bismuth quadruple therapy was non-inferior to the 14-day therapy as a first-line treatment for eradicating H. pylori infection and had no different rates of overall adverse effects, but less serious adverse events in terms of dizziness and vomiting. Funding: The National Science and Technology Council and Ministry of Health and Welfare, Taiwan.

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.

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.

Corrigendum: A randomized controlled trial of a coping-focused family resilience intervention program for breast cancer patients: study protocol.

[This corrects the article DOI: 10.3389/fpsyg.2022.968154.].

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.).

Diagnosis and treatment of primary seminoma of the prostate: A case report and review of literature.

BACKGROUND: Primary seminoma of the prostate (PSP) is a rare type of extragonadal germ cell tumour that is easily misdiagnosed, owing to the lack of specific clinical features. It is therefore necessary for clinicians to work toward improving the accuracy of PSP diagnosis. CASE SUMMARY: A 59-year-old male patient presenting with acute urinary retention was admitted to a local hospital. A misdiagnosis of benign prostatic hyperplasia led to an improper prostatectomy. Histopathology revealed PSP invading the bladder neck and bilateral seminal vesicles. Further radiotherapy treatment for the local lesion was performed, and the patient had a disease-free survival period of 96 mo. This case was analysed along with 13 other cases of PSP identified from the literature. Only four of the cases (28.6%) were initially confirmed by prostate biopsy. In these cases, imaging examinations showed an enlarged prostate (range 6-11 cm) involving the bladder neck (13/14). Of the 14 total cases, 11 (78.6%) presented typical pure seminoma cell features, staining strongly positive for placental alkaline phosphatase, CD117, and OCT4. The median age at diagnosis was 51 (range 27-59) years, and patients had a median progression-free survival time of 48 (range 6-156) mo after treatment by cisplatin-based chemotherapy combined with surgery or radiotherapy. The remaining three were cases of mixed embryonal tumours with focal seminoma, which had clinical features similar to those of pure PSP, in addition that they also had elevated serum alpha-fetoprotein, beta-human chorionic gonadotropin, and lactose dehydrogenase. CONCLUSION: PSP should be considered in patients younger than 60 years with an enlarged prostate invading the bladder neck. Further prostate biopsies may aid in proper PSP diagnosis. Cisplatin-based chemotherapy is still the main primary therapy for PSP.

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).

Design and Implementation of Taizhou Integrated Prostate Screening.

A community-based prostate cancer screening program was conducted to assess the morbidity and associated factors for prostate cancer among the subpopulation of men aged ≥50 years in Taizhou, China. Taizhou Integrated Prostate Screening (TIPS) is a large, observational, population-based study of prostate cancer screening data based on serum prostate-specific antigen (PSA) concentrations. A pilot census of all male residents aged 50 years or older was conducted in Luqiao District, one of the field sites of the TIPS cohort in the city of Taizhou, Zhejiang. The interviewer-administered questionnaire evaluated demographic characteristics and environmental exposure factors. A total of 1,806 out of 3,516 participants completed the questionnaire. The overall prevalence of PSA ≥4 ng/mL was 11.5%, and included participants at low risk (9.2%), moderate risk (1.7%), and high risk (0.6%). Participants aged 60-69, 70-79, and ≥80 years had a 2.7-fold, 4.2-fold, and 6.5-fold higher risk of elevated PSA, respectively, in comparison with those aged 50 to 59 years (p < .001). Eighteen patients were diagnosed with prostate cancer, of whom 11 (61.1%) underwent radical surgery. This community-based PSA screening program indicated the results for early detection of prostate cancer among men aged ≥50 years. Early screening and appropriate clinical therapy for the management of prostate cancer are essential in this subpopulation.

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).

A randomized controlled trial of a coping-focused family resilience intervention program for breast cancer patients: Study protocol.

Background: Breast cancer patients and their families are under various pressures in the process of disease diagnosis and treatment, which seriously threaten their physical and mental health. Findings from existing research suggest that good family resilience can help breast cancer families better adapt and cope with adversity and challenges. However, there are only a few intervention studies on family resilience and no intervention studies on resilience among the families of breast cancer patients. Therefore, this study aims to explore appropriate measures to improve the resilience level of breast cancer families and help them better cope with the disease. Objective: The purpose of this study protocol is to demonstrate a coping-focused family resilience intervention to increase the level of resilience in the families of breast cancer patients and help them better cope with adversity. Methods: The trial will recruit 80 breast cancer families and randomly assign them to experimental and control groups in a 1:1 ratio. The control group will receive routine care, and the intervention group will receive a 6-week one-on-one online family resilience intervention based on the control group. Two groups of subjects will be assessed at baseline and at 1 week, 1 month, and 3 months after the intervention. The primary outcome is family resilience, and the secondary outcomes are coping style, social support, family disease burden, and levels of anxiety and depression. Expected results: We hypothesized that after the intervention, the intervention group would have significantly higher levels of family resilience than the preintervention and control groups. In the intervention group, other aspects related to family resilience, such as family disease burden and anxiety and depression levels of patients and their families, were significantly alleviated, and disease coping and social support levels were improved accordingly. Discussion: If the program works, it can help breast cancer families identify family strengths and resources to proactively address challenges so that families can successfully navigate the crisis and patient and family recovery can be facilitated. It can also provide a practical path for clinical workers to help breast cancer families adjust rationally. Clinical Trial Registration: This study has been registered in the Chinese Clinical Trials Registry (Registration Number: http://www.chictr.org.cn/ChiCTR2100052108).

DefectTrack: a deep learning-based multi-object tracking algorithm for quantitative defect analysis of in-situ TEM videos in real-time.

In-situ irradiation transmission electron microscopy (TEM) offers unique insights into the millisecond-timescale post-cascade process, such as the lifetime and thermal stability of defect clusters, vital to the mechanistic understanding of irradiation damage in nuclear materials. Converting in-situ irradiation TEM video data into meaningful information on defect cluster dynamic properties (e.g., lifetime) has become the major technical bottleneck. Here, we present a solution called the DefectTrack, the first dedicated deep learning-based one-shot multi-object tracking (MOT) model capable of tracking cascade-induced defect clusters in in-situ TEM videos in real-time. DefectTrack has achieved a Multi-Object Tracking Accuracy (MOTA) of 66.43% and a Mostly Tracked (MT) of 67.81% on the test set, which are comparable to state-of-the-art MOT algorithms. We discuss the MOT framework, model selection, training, and evaluation strategies for in-situ TEM applications. Further, we compare the DefectTrack with four human experts in quantifying defect cluster lifetime distributions using statistical tests and discuss the relationship between the material science domain metrics and MOT metrics. Our statistical evaluations on the defect lifetime distribution suggest that the DefectTrack outperforms human experts in accuracy and speed.

Direct transformation of equilateral hexagonal Frank vacancy loops to stacking fault tetrahedra under thermal fluctuation.

Stacking fault tetrahedra (SFTs) are highly interesting three-dimensional vacancy defects in quenched, plastically deformed or irradiated face-centered-cubic metals and have a significant impact on the properties and subsequent microstructural evolution of the materials. Their formation mechanism and stability relative to two-dimensional vacancy loops are still debated. Equilateral hexagonal Frank vacancy loops (faulted, sessile) observed in microscopy have been considered unable to directly transform to SFTs due to separation of Shockley partial dislocations as well as embryonic stacking faults. Here using sufficiently long (up to tens of nanoseconds) molecular dynamic simulations, we demonstrate that such a transformation can in fact take place spontaneously at elevated temperatures under thermal fluctuation, reducing potential energy of defected atoms by <0.05 eV/atom. The transformation becomes easier with increasing temperature or decreasing loop size.

Clinical Benefit of Niraparib to TKI/mTORi-Resistance Metastatic ccRCC With BAP1-Frame Shift Mutation: Case Report and Literature Review.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer. The top four mutant genes affecting the occurrence and progression of ccRCC are VHL, PBRM1, BAP1, and SETD2, respectively. Tyrosine kinase/mammalian target of rapamycin inhibitors (TKI/mTORis) with or without immunotherapy are the standard and effective therapy to metastatic ccRCC. Once TKI/mTORis fail to ccRCC, there is still a lack of other effective therapies. In this study, we reported a case in which a metastatic ccRCC patient (T2aN1M1) presented resistance after a 28-month treatment by sorafenib-axitinib-everolimus (TKI-TKI-mTORi). Subsequently, a frame shift pathogenic mutation, c.799_800del (p.Q267fs) in the exon10 of BAP1 in ccRCC, was revealed by targeted sequencing. Oral administration of nilapanib (PARP inhibitor) was further given, which may provide a new therapy for TKI/mTORi-resistance metastatic ccRCC. Fortunately, a partial response has been achieved and lasted for 5 months. Since the frequency of BAP1 mutations in ccRCC patients was approximately 10%-20%, as reported previously, we also tried to explore the potential mechanisms benefitting from the nilapanib. Moreover, the literature concerning BAP1 mutation and associated cancers including ccRCC is reviewed.

Association between health behaviours and the COVID-19 vaccination: risk compensation among healthcare workers in Taizhou, China.

This study is conducted to explore the association between health behaviors and the COVID-19 vaccination based on the risk compensation concept among health-care workers in Taizhou, China. We conducted a self-administered online survey to estimate the health behaviors among the staff in a tertiary hospital in Taizhou, China, from May 18 to 21 May 2021. A total of 592 out of 660 subjects (89.7%) responded to the questionnaire after receiving an e-poster on WeChat. Subjects who had been inoculated with the COVID-19 vaccine were asked to mention the differences in their health behaviors before and after the vaccination. The results showed that there were no statistical differences in health behaviors between vaccinated and unvaccinated groups, except in terms of the type of gloves they used (62.8% in the vaccinated group and 49.2% in the unvaccinated group, p = .048). Subjects who received earlier COVID-19 vaccinations exhibited better health behaviors (22.40% increased for duration of wearing masks (P = .007), 25.40% increased for times of washing hands (P = .01), and 20.90% increased for times of wearing gloves (P = .01)). Subjects also revealed better health behaviors (washing hands, wearing gloves, and wearing masks) after vaccination compared to that before. In conclusion, concept of risk compensation was not applied in our findings. The health behaviors did not reduce after the COVID-19 vaccination, which even may improve health behaviors among health-care workers in the hospital setting.

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.

Optimal Intervals of Ultrasonography Screening for Early Diagnosis of Hepatocellular Carcinoma in Taiwan.

Importance: There are different clinical practices regarding ultrasonography screening intervals for hepatocellular carcinoma (HCC) despite recommendations from international guidelines. Objective: To evaluate whether ultrasonography screening using intervals suggested by international guidelines is associated with cancer stage shifting, reductions in mortality, and improved quality of life (QoL) for patients with HCC. Design, Setting, and Participants: This nationwide comparative effectiveness research study estimated lifetime survival functions using interlinkages of 3 databases from Taiwan-the Taiwan National Health Insurance, Taiwan National Cancer Registry, and National Mortality Registry-combined with QoL measurements obtained from National Cheng Kung University Hospital. In total, 114 022 patients listed as having newly diagnosed HCC from 2002 through 2015 in the Taiwan National Cancer Registry were followed up until 2017. The QoL values of 1059 patients with HCC who visited National Cheng Kung University Hospital were prospectively measured with the European QoL-5 dimensions questionnaire from 2011 through 2019. Patients were categorized based on the time between their last ultrasonography screening and the index date (90 days prior to HCC diagnosis) as 1 of 5 subcohorts: 6 months (0-6 months), 12 months (7-12 months), 24 months (13-24 months), 36 months (25-36 months), and longer than 36 months (no screening in the previous 3 years). Data were analyzed from April 2020 to April 2021. Main Outcomes and Measures: Life expectancy, quality-adjusted life expectancy, and loss of life expectancy or loss of quality-adjusted life expectancy compared with age-, sex-, and calendar year-matched cohorts. Results: There were 59 194 patients with Barcelona Clinic Liver Cancer staging information, including 42 081 men (mean [SD] age, 62.2 [12.6] years) and 17 113 women (mean [SD] age, 69.0 [11.2] years). There was a consistent trend showing that the longer the interval between ultrasonography examinations, the higher the loss of life expectancy and loss of quality-adjusted life expectancy for both sexes. Loss of quality-adjusted life expectancy values for male subcohorts were 10.0 (95% CI, 9.1-10.9) quality-adjusted life-years (QALYs) for ultrasonography screening intervals of 6 months, 11.1 (95% CI, 10.4-11.8) QALYs for 12 months, 12.1 (95% CI, 11.5-12.7) QALYs for 24 months, 13.1 (95% CI, 12.6-13.6) QALYs for 36 months, and 14.6 (95% CI, 14.2-15.0) QALYs for longer than 36 months. Loss of quality-adjusted life expectancy values for female subcohorts were 9.0 (95% CI, 8.3-9.6) QALYs for 6 months, 9.7 (95% CI, 9.2-10.2) QALYs for 12 months, 10.3 (95% CI, 9.8-10.7) QALYs for 24 months, 10.7 (95% CI, 10.2-11.1) QALYs for 36 months, and 11.4 (95% CI, 11.0-11.8) QALYs for longer than 36 months. Patients with underlying hepatitis B virus infection or cirrhosis had the greatest improvement in life expectancy with shorter screening intervals. Conclusions and Relevance: Regular ultrasonography screening with intervals less than 6 to 12 months may be associated with early detection of HCC, save lives, and improve the quality of life for patients with HCC from a lifetime perspective.

UPLC-ESI-Q-TOF/MS Based Metabolic Profiling of Protosappanin B in Rat Plasma, Bile, Feces, Urine and Intestinal Bacteria Samples.

BACKGROUND: Caesalpinia sappan L. is a traditional medicinal plant that is used to promote blood circulation and treat stroke in China. Protosappanin B (PTB) is a unique homoisoflavone compound isolated from Sappan Lignum (the heartwood of Caesalpinia sappan L). In a previous study, the metabolic fate of PTB remained unknown. OBJECTIVE: To explore whether PTB is extensively metabolized, the metabolites of PTB in bile, plasma, urine, feces, and intestinal bacteria samples in rats were investigated. METHODS: The biosamples were investigated by ultraperformance liquid chromatography combined with time-offlight mass spectrometry (UPLC-TOF-MS/MS) with MetabolitePilot software. RESULTS: 28 metabolites were identified in the biosamples: 18 metabolites in rat bile, 8 in plasma, 20 in feces, 7 in urine and 2 in intestinal bacteria samples. Both phase I and phase II metabolites were observed. Metabolite conversion occurred via 9 proposed pathways: sulfate conjugation, glucuronide conjugation, bis-glucuronide conjugation, glucose conjugation, dehydration, oxidation, hydrolysis, methylation and hydroxymethylene loss. The metabolic pathways differed among biosamples and exhibited different distributions. Among these pathways, the most important was sulfate and glucuronide conjugation. CONCLUSION: The results showed that the small intestinal and biliary routes play an important role in the clearance and excretion of PTB. The main sites of metabolism in the PTB chemical structure were the phenolic hydroxyl and the side-chains on the eight-element ring.